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ImmixBio Announces Clinical Trial and Supply Agreement with BeiGene to Evaluate Combination of IMX-110 and Tislelizumab in Solid Tumors | Small…

Posted: August 29, 2021 at 1:49 am

DetailsCategory: Small MoleculesPublished on Saturday, 28 August 2021 18:14Hits: 328

Novel Approach Combining ImmixBio Tissue Specific Therapeutics (TSTx) with Immunotherapies Could Expand the Population Of Cancer Patients Experiencing Extended Remissions

LOS ANGELES, CA, USA I August 27, 2021 I Immix Biopharma, Inc. ("ImmixBio") today announced a clinical trial and supply agreement with BeiGene, Ltd. to evaluate the safety, tolerability and efficacy of combining IMX-110, a Tissue Specific Therapeutic with TME Normalization Technology, with BeiGene's anti-PD-1 antibody tislelizumab, for the treatment of various solid tumors, in the U.S. and internationally.

Under the terms of the agreement, ImmixBio will evaluate the combination of IMX-110 with tislelizumab in a Phase 1/2a trial in patients with advanced solid tumors.


"ImmixBio is proud to showcase our Tissue Specific Therapeutics (TSTx) platform to the world. Promising data from our ongoing IMX-110 clinical trial, from pre-clinical studies in a genetic mouse model of pancreatic cancer showing IMX-110 turning "cold" tumors "hot," and IMX-110 in combination with murine anti-PD-1 demonstrating extended survival in a genetic mouse model of pancreatic cancer versus multi-drug combinations in the literature, have demonstrated substantial rationale to combine IMX-110 and tislelizumab," said Ilya Rachman, MD, PhD ImmixBio CEO. "We have high hopes that IMX-110 in combination with tislelizumab could expand the population of cancer patients experiencing extended remissions."

About IMX-110

IMX-110 is a Tissue-Specific Therapeutic built on ImmixBio's TME Normalization Technology encapsulating a poly-kinase inhibitor and apoptosis inducer delivered deep into the tumor micro-environment, or TME. ImmixBio's TME Normalization Technology enables IMX-110 to circulate in the bloodstream, then exit through porous tumor blood vessels, and accumulate in the TME. IMX-110 then simultaneously attacks all 3 components of the TME (cancer associated fibroblasts, or CAFs; tumor-associated macrophages/immune cells, or TAMs, and cancer itself), severing the critical lifelines between the tumor and its metabolic and structural support. IMX-110's TME Normalization Technology causes tumor apoptosis, a non-inflammatory tumor-cell death (vs. necroptosis, which results in repeat reignition of the inflammatory cascade leading to tumor progression).

IMX-110 is currently being evaluated in a phase 1b/2a open-label, dose-escalation/dose-expansion safety, tolerability and pharmacokinetic study in patients with advanced solid tumors in the United States and Australia.

About Tislelizumab

Tislelizumab (BGB-A317) is a humanized IgG4 anti-PD-1 monoclonal antibody specifically designed to minimize binding to FcR on macrophages. In pre-clinical studies, binding to FcR on macrophages has been shown to compromise the anti-tumor activity of PD-1 antibodies through activation of antibody-dependent macrophage-mediated killing of T effector cells. Tislelizumab is being developed internationally as a monotherapy and in combination with other therapies for the treatment of a broad array of both solid tumor and hematologic cancers.

The China National Medical Products Administration (NMPA) has granted tislelizumab market authorization in four indications, including full approval for first-line treatment of patients with advanced squamous non-small cell lung cancer (NSCLC) in combination with chemotherapy. Tislelizumab is not approved for use outside of China.

In January 2021, BeiGene and Novartis entered into a collaboration and license agreement granting Novartis rights to develop, manufacture, and commercialize tislelizumab in North America, Europe, and Japan.

About ImmixBio

ImmixBio is a clinical-stage biopharmaceutical company pioneering a novel class of Tissue-Specific Therapeutics (TSTx) in oncology and inflammation. Our lead asset, IMX-110, is currently in phase 1b/2a clinical trials for solid tumors in the United States and Australia. Our proprietary System Multi-Action RegulaTors SMARxT Tissue-Specific Platform produces drugs that accumulate at intended therapeutic sites at 3-5 times the rate of conventional medicines. Our TME Normalization Technology allows our drug candidates to circulate in the bloodstream, exit through tumor blood vessels and simultaneously attack all components of the tumor micro-environment, or TME. We have uncovered fundamental biological systems that link oncology and inflammation. In addition to oncology, our pipeline includes Tissue-Specific Biologic candidates to treat inflammatory bowel disease, including ulcerative colitis and Crohn's disease. Learn more at http://www.immixbio.com

SOURCE: ImmixBio

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ImmixBio Announces Clinical Trial and Supply Agreement with BeiGene to Evaluate Combination of IMX-110 and Tislelizumab in Solid Tumors | Small...

Laekna Therapeutics Receives IND Approvals in China and US for Phase Ib/III Global Multi-center Clinical Study of Afuresertib in combination with…

Posted: at 1:49 am

SHANGHAI and WAREN, New Jersey, Aug. 26, 2021 /PRNewswire/ -- Laekna Therapeutics announced today that the Center for Drug Evaluation (CDE), the National Medical Products Administration (NMPA) of China has approved the Investigational New Drug (IND) application of its Category 1 new drug candidate afuresertib (LAE002) in combination with anti-estrogen receptor drug fulvestrant in the Phase Ib/III clinical trial of patients with locally advanced or metastatic hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) breast cancer.

This global multi-center clinical trial will be initiated simultaneously in the United States and China a month earlier than previously planned. The Phase III global registrational study will be started soon after afuresertib plus fulvestrant demonstrates proof of concept results in tolerability and anti-tumor efficacy in patients enrolled in the Phase Ib study.

Clinical trials of afuresertib cover four different cancers

Afuresertib (LAE002) is a clinically proven, with a first-in-class potential, highly potent small-molecule pan-AKT inhibitor. Currently, afuresertib is being studied in global clinical studies in four different cancers including ovarian cancer, prostate cancer, triple-negative breast cancer, and HR+/HER2- breast cancer. In the four ongoing clinical trials, afuresertib is explored in combination with chemotherapy, anti-androgen therapy, anti-PD-L1 monoclonal antibody, and anti-estrogen therapy, respectively.

Aiming to be a first-in-class AKT inhibitor

"The IND approval came one month earlier than expected, demonstrating the NMPA's prioritization and support for the clinical development of new treatment options for drug resistant breast cancer patients. It also showcases effective collaboration between our teams in the US and China," said Dr. Chris Lu, Chairman and Chief Executive Officer of Laekna Therapeutics. "We continue to be a tier-1 player globally in the development of AKT kinase inhibitors. We are accelerating multiple clinical trials to potentially make afuresertib a potential first-in-class therapy."

Striving to address drug resistance in patients with HR+/HER2- breast cancer

Breast cancer is the most common cancer among women worldwide. About 62% and 68% of all breast cancer patients in China and the US are HR+/HER2- respectively. Current treatment are available in the form of first- and second-line endocrine/anti-estrogen therapies and/or in combination of CDK4/6 inhibitors, or chemotherapy, however, the patients often develop drug resistance after a period of time.

"The HR+/HER2- subtype accounts for the largest subgroup of breast cancer. One of the urgent unmet medical needs is to provide a new therapy after patients develop resistance to prior standard of care treatments. It will also help significantly improve the clinical outcomes and quality of life for patients with breast cancer," said Dr. Yue Yong, Chief Medical Officer of Laekna Therapeutics. "Combination therapies based on afuresertib are being explored in clinical trials in patients with various types of drug-resistant cancers, and results showed preliminary anti-tumor efficacy and manageable safety profiles, particularly in ovarian and breast cancers. We expect these new treatment options will benefit patients and provide doctors with better choices in treating patients with drug-resistant tumors."

About AfuresertibLAE002

Afuresertib (LAE002) is a differentiated oral, small molecule pan-AKT kinase inhibitor that has been investigated in over 10 Phase 1/2 clinical trials, including ovarian cancer, gastric cancer, multiple myeloma, and melanoma. These studies have demonstrated that afuresertib has strong anti-cancer activities and a tolerable safety profile. The global randomized, open-label, multi-center Phase 2 PROFECTA-II clinical trial of afuresertib is the world's first registration-directed clinical study of a pan-AKT kinase inhibitor to treat platinum-resistant ovarian cancer.

In recent years, AKT (a serine/threonine-protein kinase) has emerged as an important mechanism in oncology, as it plays an important role in regulating various cell functions such as metabolism, survival, proliferation, tissue invasion, and chemotherapy resistance. PTEN deletion and AKT/PIK3CA alteration may lead to excessive activation of the AKT signaling pathways, which is one of the key drivers for cancer growth. The increased activation of the AKT signaling pathway is particularly common in recurrent ovarian cancer, breast cancer, and prostate cancer.

About Laekna Therapeutics

Founded in December 2016, Laekna Therapeutics is an emerging innovative pharma company based in China's "Zhangjiang Pharma Valley" and New Jersey in the US, focusing on developing new ground-breaking innovative therapies to treat cancer and liver diseases.

Laekna Therapeutics has adopted a two-pronged strategy in new drug development. On one hand, it continues to enrich its portfolio by introducing global new drugs with the clinical Proof of Concept. The company has obtained the global exclusive rights of four new drug candidates from Novartis. On the other hand, the company's self-developed innovative drugs will soon enter clinical development stage.

Laekna has set up a team of top global pharmaceutical talent. Its leadership team members each have over 20 years of experience in new drug development in China and the US, with an exceptional track record in R&D, new drug approvals and commercialization. Laekna is committed to a science-based, innovation-driven approach to create an international leading clinical research and development platform for the development of first-in-class and best-in-class innovative drugs.

The detail Laekna Therapeutics information can be found from the website: http://www.laeknatp.com

Contact Laekna TherapeuticsLeah Liu CFO[emailprotected]

Media Cleo Zhang 86-18516226288[emailprotected]

Corporate and Business DevelopmentGuy Rosenthal (US)[emailprotected]

SOURCE Laekna Therapeutics

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Laekna Therapeutics Receives IND Approvals in China and US for Phase Ib/III Global Multi-center Clinical Study of Afuresertib in combination with...

Scientific Workforce Diversity and Health Disparities Research Programs – National Institute on Aging

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With the goal of advancing the most innovative scientific ideas from investigators of all ethnic, racial, and cultural backgrounds, NIA works to diversify the aging research workforce, both within our institute and through the grantees we support. Additionally, we are committed to eliminating health disparities in research through a variety of ways, including novel recruitment initiatives to incorporate diverse participants in our clinical studies and trials.

NIA further seeks to understand the environmental, sociocultural, behavioral, and biological drivers of health inequities and disparities related to aging and diseases such as Alzheimers and related dementias. We support research to develop strategies for the improvement of health among midlife and older adults in underrepresented groups who experience health inequities or disparities. These priorities are outlined in NIAs strategic directions for health disparities research and reflected within NIAs Health Disparities Research Framework.

NIA leads initiatives, co-funds programs, and participates in NIH-wide efforts to improve research workforce diversity by increasing the number of trained researchers from underrepresented groups who can become leaders in aging research. Learn more about NIAs training opportunities for special populations.

NIAs Office of Special Populations (OSP) serves to support and strengthen the institutes work to understand and address health disparities in older adults.

The annual NIA Directors Regional Meeting provides an opportunity for scientists who might be less aware of NIAs funding opportunities in aging research, and/or are working at universities that may not have received significant NIH funding in the past, to interact with NIA leadership. Led by OSP, agendas feature types of awards available to researchers and trainees new to aging research or interested in health disparities research, as well as to those who are underrepresented in aging research. NIAs goals are to provide information on existing opportunities for research and training; provide hands-on technical assistance in grant writing; solicit advice on the design of new research opportunities; and discuss strategies for recruiting underrepresented students and investigators to aging research.

For decades, NIAs National Advisory Council on Aging (NACA) has convened the Task Force on Minority Aging Research as part of its meetings three times each year. Managed by OSP and the Minority Working Group, this task force was created to advise NACA on initiatives to increase the representation of minorities in aging research. It provides a quarterly summary of NIAs diversity programs and initiatives, including updates on meetings and conferences, diversity and health disparities research, and training programs and initiatives. NIA often invites renown health disparities in aging researchers to present at NACA.

The Butler-Williams Scholars Program, formerly known as the Summer Institute on Aging, provides unique opportunities for junior faculty and researchers new to the field to gain insight about aging research. The prestigious annual summer program builds upon a rich history of NIAs work to highlight different perspectives in aging research through dynamic presentations and small group discussions. NIA encourages researchers who are interested in health disparities research related to aging, and those who are underrepresented in aging research, to apply.

The NIA MSTEM Advancing Diversity in Aging Research through Undergraduate Education (ADAR) program is designed to enhance diversity in undergraduate science education. Through ADAR, NIA has provided more than 300 college students with coursework, lab instruction, and mentoring in aging related research. Learn more about the ADAR program and read profiles of students who have participated.

NIA's Diversity and Re-entry Supplement programs support the development of eligible trainee-candidates who seek independent careers in aging and geriatrics research and meet our goal to enhance workforce diversity. Supplemental awards provide funds to support a mentor-directed opportunity for a trainee-candidate to develop the critical thinking skills, scientific technical expertise, and professional acumen essential for career advancement in the biomedical, behavioral, clinical, or social sciences. Learn more about NIAs training opportunities for special populations and supplement programs.

NIA is committed to training researchers for lifetime careers in the biomedical and behavioral sciences. Through its Intramural Research Program (IRP), NIA offers multiple training opportunities in both laboratory and clinical medicine, along with a wealth of valuable resources.

The Diversity in Aging Research Pipeline Program (DARPP) is designed to develop and expose underrepresented and socioeconomically disadvantaged students to aging research. High school, college, graduate, medical, and postdoctoral students receive training from NIA IRP scientists in a highly mentored, structured environment. Students receive long-term support and follow-through during their experience with NIA and beyond.

NIAs Summer Trainee in Aging Research (STAR) Program offers unique internship opportunities for underrepresented and socioeconomically disadvantaged high school, college, graduate, and medical students. Based in Baltimore, internships last from eight to 10 weeks during the summer, and students get hands-on experience in scientific research settings and attend weekly seminars presented by NIA scientists. At the conclusion of the summer program, students present the data developed from their research projects at the NIA Summer Student Poster Day. Program participants receive a stipend to participate.

Many complex and interconnected factors can affect older adults health and quality of life. To develop and implement effective interventions to address health disparities among various populations, NIA supports and conducts research to:

Researchers from underrepresented groups or those interested in health disparities aging research can contact program officers for specific areas of interest, and learn how to find NIA funding opportunities, apply for grants and funding, and how the NIA peer review process works. Also see a full list of NIA-wide active funding opportunities, NIA-wide Alzheimers Disease and Alzheimers disease and related dementias (AD/ADRD)funding opportunities, and Small Business Innovation Research (SBIR) and Small Business Technology Transfer (STTR) funding opportunities.

The NIA Health Disparities Research Framework, overseen by OSP, outlines four key levels of analysis related to disparities research environmental, sociocultural, behavioral, and biological with priority focus areas in each category. Using the framework as a guide, NIA has awarded more than $250 million in research awards since 2015 to explore and address these determinants of health disparities related to aging.

The National Plan to Address Alzheimers Disease provides a framework for reaching our nations goal of effectively preventing and treating Alzheimers disease and related dementias by 2025. To this end, NIA led the development of implementation research milestones, which include research on health disparities in Alzheimers and related dementias and recruitment and participation of diverse participants clinical studies.

Through its Resource Centers for Minority Aging Research (RCMAR), since 1997, NIA has been mentoring promising scientists from underrepresented groups and playing a critical role in training the next generation of diverse researchers. Located at universities across the United States, the centers focus on health disparities and minority aging issues as a major part of their research education programs. In 2018, the RCMAR program was expanded to support additional centers focused on Alzheimers disease and related dementias research.

NIAs Intramural Research Program (IRP) scientists conduct a broad range of multidisciplinary, investigator-initiated research, including studies on health conditions and aging in diverse populations. Goals include investigating the biology of health disparities in the context of aging and disentangling the interaction between socioeconomic status and race in the development of age-associated health disparities. Other goals include mentoring the next generation of leaders in the epidemiology of aging, health disparities, and behavior.

Through the Healthy Aging in Neighborhoods of Diversity across the Life Span Study (HANDLS), NIA seeks to understand and address health disparities associated with race and socio-economic status in several Baltimore neighborhoods. Visit the Health Disparities Research Section to learn more.

One of the biggest hurdles in advancing Alzheimers and related dementias and other aging research is recruitment and retention of clinical study and trial participants, particularly those from underrepresented populations. It is important for clinical studies and trials to have participants of different ages, sexes, races, and ethnicities. When research involves a group of people who are similar, the findings may not be relevant to broader groups of individuals. When clinical trials include diverse participants, the study results may have a much wider applicability. NIA seeks to engage a more diverse range of older adults for the many clinical trials and studies it conducts and supports, including prevention and intervention trials on Alzheimers and related dementias.

As part of the National Plan to Address Alzheimers Disease, NIA intensified efforts to outline practical, proactive approaches to help researchers recruit and retain diverse volunteers for a growing number of studies in Alzheimers and related dementias. NIA convened stakeholders to develop a National Recruitment Strategy featuring goals and approaches for increasing and diversifying research participants in Alzheimers and related dementias research. Developed with the Alzheimers Association and other stakeholders, the National Strategy focuses on four overarching themes: increasing awareness and engagement nationally; building and improving capacity and infrastructure at study sites; engaging local communities and support participants; and developing an applied science of recruitment.

NIA's new Clinical Research Operations and Management System (CROMS) provides the capability to track, report, and manage NIA grantee clinical research data including participant enrollment in supported studies and other scientific portfolio activities in real time. The CROMS resource is enabling NIA and its funded investigators to intervene early to assist with enrollment challenges and support recruitment and retention of underrepresented populations in Alzheimers and related dementias research.

Outreach Pro is a new online research tool to help increase participation by traditionally underrepresented populations in clinical trials and studies on Alzheimers and related dementias. Unveiled at the Alzheimer's Association International Conference (AAIC) in July 2021, Outreach Pro enables those involved with leading clinical research to create and customize participant recruitment communications such as websites, handouts, videos, and social media posts. It is an integral part of NIAs efforts to implement the National Strategy for Recruitment and Participation in Alzheimers and Related Dementias Clinical Research.

NIAs Alzheimer's & Dementia Outreach, Recruitment & Engagement (ADORE) repository is a searchable collection of resources on topics related to the engagement, recruitment, and retention of diverse participants in dementia clinical trials and studies. Researchers, community advocates, and study coordinators can search the ADORE database to find materials and strategies to help recruit participants.

A core component of NIAs mission is to disseminate aging-related information and research advances to diverse audiences including the public, policymakers, advocates, health care professionals, the scientific community, and the media. NIAs website, social media, email alerts, print, video, and other communications channels provide evidence-based information on aging health topics and research, grants and funding, training and career development, and clinical trials.

NIAs weekly blog for researchers provides updates on NIA funding policies and research priorities, including training opportunities and health disparities research priorities. Read blogs about diversity-related issues.

NIA also develops materials for special audiences and diverse populations, including non-English language materials and materials for those with limited literacy. NIAs Spanish-language website offers evidence-based health information to Spanish speaking audiences.

NIA strongly supports UNITE, NIHs initiative to end structural racism and racial inequities in biomedical and behavioral research. A collaborative, NIH-wide effort, UNITE is designed to establish an equitable and civil culture within the biomedical research enterprise and to reduce barriers to racial equity in the biomedical research workforce.

Read NIA Director Dr. Richard J. Hodess UNITE announcement and the NIA Office of Special Populations Director Dr. Patricia Joness blog post about the initiative and related funding opportunities.

NIA participates in the NIH Community Engagement Alliance (CEAL) Against COVID-19 Disparities initiative. The goal is to build long-lasting partnerships in communities hardest-hit by COVID-19, as well as to improve diversity and inclusion in our research response to this pandemic.

The Rapid Acceleration of Diagnostics (RADxSM) initiative is a national call for scientists and organizations to speed innovation in the development, commercialization, and implementation of technologies for COVID-19 testing. NIA co-led the Rapid Diagnostic Accelerator for Underrepresented Populations (RADxUP) funding opportunity announcements, which are focused on COVID-19 vulnerable populations, with our partners at the NIH National Institute of Minority Health and Health Disparities and other NIH institutes, centers, and offices. NIA also co-led NIH efforts to strengthen data collection on COVID-19 to rapidly assess the needs and impact of COVID-19 across different population groups, particularly vulnerable populations. Learn more about NIA's support of the RADxSM initiative.

NIA has played a leadership role in guiding NIH Inclusion Across the Lifespan policy and convening biannual workshops to support updating and implementing this policy in clinical research. The policy mandates that diverse participants of all ages be included in human research, particularly children, older adults, and underrepresented/underserved populations, unless there is a scientific or ethical reason for exclusion of any age category. These groups have specific and unique health issues that must be examined as we study new interventions that ultimately inform health care.

NIA also participates in the NIH Diversity Catalysts program, which is led by the NIH Office of Scientific Workforce Diversity. The goal is to implement and evaluate evidence-based diversity and inclusion strategies across the NIH.

NIA supports the NIH Women of Color Research Network (WOCRN), an online community working to address issues faced by women and minorities in scientific careers. WOCRN offers links to current events, resources, and valuable connections.

Learn more about how NIH promotes a scientific workforce and the NIH offices working on scientific workforce diversity issues.

Scientific Workforce Diversity and Health Disparities Research Programs - National Institute on Aging

BridgeBio Pharma and LianBio Announce First Patient Treated in Phase 2a Trial of Infigratinib in Patients with Gastric Cancer and Other Advanced Solid…

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PALO ALTO, Calif. & SHANGHAI & PRINCETON, N.J.--(BUSINESS WIRE)--LianBio, a biotechnology company dedicated to bringing paradigm-shifting medicines to patients in China and other major Asian markets, and BridgeBio Pharma, Inc. (Nasdaq: BBIO) today announced the first patient has been treated in a Phase 2a clinical trial of infigratinib in patients with locally advanced or metastatic gastric cancer or gastroesophageal junction adenocarcinoma with fibroblast growth factor receptor-2 (FGFR2) gene amplification and other advanced solid tumors with FGFR genomic alterations.

Infigratinib is a potent and selective FGFR inhibitor that has demonstrated compelling clinical activity across multiple tumor types with FGFR alterations, said Yizhe Wang, Ph.D., chief executive officer of LianBio. Given the disproportionately high prevalence rate of gastric cancer in China, LianBio is pursuing a region-specific development strategy focused on this area of great unmet need. This study marks LianBios first trial initiation and demonstrates our continued progress in delivering potentially transformational medicines to patients in Asia.

TRUSELTIQ (infigratinib) is an oral selective inhibitor of FGFR1-3 that is approved in the United States for the treatment of patients with previously treated, unresectable locally advanced or metastatic cholangiocarcinoma with a FGFR2 fusion or other rearrangement as detected by an FDA-approved test. It is also being further evaluated in clinical trials based on demonstration of clinical activity in patients with advanced urothelial carcinoma with FGFR3 genomic alterations. LianBio in-licensed rights from BridgeBio for infigratinib for development and commercialization in Mainland China, Hong Kong and Macau.

The Phase 2a trial is a multicenter, open-label, single-arm study in China designed to evaluate the safety and efficacy of infigratinib in patients with locally advanced or metastatic gastric cancer or gastroesophageal junction adenocarcinoma with FGFR2 gene amplification and other advanced solid tumors with FGFR alterations. The primary endpoint is objective response rate (ORR). Secondary endpoints include duration of response, safety, disease control rate, progression-free survival and overall survival.

Preclinical data have demonstrated the potential infigratinib may have for patients with gastric cancer. These results, published in Cancer Discovery, demonstrated tumor regression in multiple in vivo FGFR2 amplified gastric models.1

We believe that infigratinib could have a meaningful impact for people living with gastric cancer as well as many other cancers with FGFR alterations, and are pleased LianBio is initiating this clinical trial in China where more therapeutic options are needed to match the growing diagnosis rate, said BridgeBio founder and chief executive officer Neil Kumar, Ph.D. On the heels of TRUSELTIQ recently obtaining accelerated approval in the United States, we are hopeful that this trial will yield pivotal results in another subset of cancer patients as we continue to build our portfolio of oncology indications with the aim of reaching as many people in need as possible.

About TRUSELTIQ (infigratinib)

TRUSELTIQ (infigratinib) is an orally administered, ATP-competitive, tyrosine kinase inhibitor of fibroblast growth factor receptor (FGFR) that received accelerated approval from the FDA in the United States for the treatment of adults with previously treated, unresectable locally advanced or metastatic cholangiocarcinoma with a fibroblast growth factor receptor 2 (FGFR2) fusion or other rearrangement as detected by an FDA-approved test. TRUSELTIQ targets the FGFR protein, blocking downstream activity. In clinical studies, TRUSELTIQ demonstrated a clinically meaningful rate of tumor shrinkage (overall response rate) and duration of response. TRUSELTIQ is not FDA-approved for any other indication in the United States and is not approved for use by any other health authority, including any Chinese or other Asian health authority. It is currently being evaluated in clinical studies for first-line cholangiocarcinoma, urothelial carcinoma (bladder cancer), locally advanced or metastatic gastric cancer or gastroesophageal junction adenocarcinoma, and other advanced solid tumors with FGFR genomic alterations.

About BridgeBio Pharma, Inc.

BridgeBio is a biopharmaceutical company founded to discover, create, test and deliver transformative medicines to treat patients who suffer from genetic diseases and cancers with clear genetic drivers. BridgeBios pipeline of over 30 development programs ranges from early science to advanced clinical trials and its commercial organization is focused on delivering the companys first two approved therapies. BridgeBio was founded in 2015 and its team of experienced drug discoverers, developers and innovators are committed to applying advances in genetic medicine to help patients as quickly as possible. For more information visit bridgebio.com.

About LianBio

LianBios mission is to catalyze the development and accelerate availability of paradigm-shifting medicines to patients in China and other major Asian markets, through partnerships that provide access to innovative therapeutic discoveries with a strong scientific basis and compelling clinical data. LianBio collaborates with world-class partners across a diverse array of therapeutic and geographic areas to build out a broad and clinically validated pipeline with the potential to impact patients with unmet medical needs. For more information, please visit http://www.lianbio.com.

About the LianBio and BridgeBio Pharma, Inc. Strategic Alliance

In August 2020, LianBio entered into a strategic alliance with BridgeBio, a commercial-stage biopharmaceutical company focused on genetic diseases and cancers with clear genetic drivers, to develop and commercialize BridgeBios programs in China and other major Asian markets. This strategic relationship initially focuses on two of BridgeBios targeted oncology drug candidates: FGFR inhibitor infigratinib, for the treatment of FGFR-driven tumors, and SHP2 inhibitor BBP-398, in development for tumors driven by MAPK pathway mutations. The agreement also provides LianBio with preferential future access in China and certain other major Asian markets to more than 20 drug development candidates currently owned or controlled by BridgeBio. This collaboration is designed to advance and accelerate BridgeBios programs in China and other major Asian markets, allowing BridgeBio and LianBio to potentially bring innovation to large numbers of patients with high unmet need.

BridgeBio Pharma, Inc. Forward-Looking Statements

This press release contains forward-looking statements. Statements we make in this press release may include statements that are not historical facts and are considered forward-looking within the meaning of Section 27A of the Securities Act of 1933, as amended (the Securities Act), and Section 21E of the Securities Exchange Act of 1934, as amended (the Exchange Act), which are usually identified by the use of words such as anticipates, believes, estimates, expects, intends, may, plans, projects, seeks, should, will, and variations of such words or similar expressions. We intend these forward-looking statements to be covered by the safe harbor provisions for forward-looking statements contained in Section 27A of the Securities Act and Section 21E of the Exchange Act, and are making this statement for purposes of complying with those safe harbor provisions. These forward-looking statements, including statements relating to: the timing and success of the Phase 2a clinical trial of infigratinib in patients with locally advanced or metastatic gastric cancer or gastroesophageal junction adenocarcinoma with fibroblast growth factor receptor-2 (FGFR2) gene amplification, and other advanced solid tumors with FGFR genomic alterations; the planned approval of infigratinib by foreign regulatory authorities in China and the necessary clinical trial results, and timing and completion of regulatory submissions related thereto; and the competitive environment and clinical and therapeutic potential of infigratinib; reflect our current views about our plans, intentions, expectations, strategies and prospects, which are based on the information currently available to us and on assumptions we have made. Although we believe that our plans, intentions, expectations, strategies and prospects as reflected in or suggested by those forward-looking statements are reasonable, we can give no assurance that the plans, intentions, expectations or strategies will be attained or achieved. Furthermore, actual results may differ materially from those described in the forward-looking statements and will be affected by a variety of risks and factors that are beyond our control including, without limitation: the safety, tolerability and efficacy profile of infigratinib observed to date may change adversely in ex-U.S. clinical trials, ongoing analyses of trial data or subsequent to commercialization; foreign regulatory agencies may not agree with our regulatory approval strategies, components of our filings, such as clinical trial designs, conduct and methodologies, or the sufficiency of data submitted; the continuing success of the BridgeBio and LianBio strategic alliance; and potential adverse impacts due to the global COVID-19 pandemic such as delays in regulatory review, manufacturing and clinical trials, supply chain interruptions, adverse effects on healthcare systems and disruption of the global economy; as well as those set forth in the Risk Factors section of BridgeBio Pharma, Inc.s most recent Annual Report on Form 10-K filed with the U.S. Securities and Exchange Commission (SEC) and in subsequent SEC filings, which are available on the SECs website at http://www.sec.gov. Except as required by law, each of BridgeBio and QED disclaims any intention or responsibility for updating or revising any forward-looking statements contained in this press release in the event of new information, future developments or otherwise. Moreover, BridgeBio and QED operate in a very competitive environment in which new risks emerge from time to time. These forward-looking statements are based on each of BridgeBios and QEDs current expectations, and speak only as of the date hereof.

1 Guagnano, V., Kauffman, A., Wrle, S., et al. FGFR Genetic Alterations Predict for Sensitivity to NVP-BGJ398, a Selective Pan-FGFR Inhibitor. Cancer Discovery 2 (2012): 1118-1133.

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BridgeBio Pharma and LianBio Announce First Patient Treated in Phase 2a Trial of Infigratinib in Patients with Gastric Cancer and Other Advanced Solid...

Denali Therapeutics Announces Publication in Cell on New – GlobeNewswire

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SOUTH SAN FRANCISCO, Calif., Aug. 26, 2021 (GLOBE NEWSWIRE) -- Denali Therapeutics Inc. (NASDAQ: DNLI), a biopharmaceutical company developing a broad portfolio of product candidates engineered to cross the blood-brain barrier (BBB) for neurodegenerative diseases, today announced publication of preclinical proof of concept for using its Protein Transport Vehicle (PTV) to enhance brain uptake of peripherally administered progranulin (PTV:PGRN). This approach may have utility in treating certain types of frontotemporal dementia (FTD), especially FTD-GRN caused by progranulin deficiency.

Published online Thursday, August 26th, ahead of print in the September 2nd issue of Cell, the preclinical research showed that progranulin replacement therapy with Denalis PTV:PGRN rescued both neurodegeneration and microglial dysfunction in progranulin-deficient mice. The research also provides new insight into the molecular and cellular mechanisms that may contribute to FTD, identifying novel roles of progranulin in lysosomal function and lipid metabolism, as well as lysosome biomarkers with potential clinical utility.

This preclinical research demonstrates that our Protein Transport Vehicle can enhance the uptake of peripherally administered progranulin by multiple cell types in the brain, including neurons and microglia, said Denalis Chief Scientific Officer Joseph Lewcock, Ph.D. In addition, the improved mechanistic understanding of progranulins role in lysosomal function indicates that our therapeutic strategy with PTV:PGRN may be the most direct and effective way to increase progranulin levels in lysosomes for the potential treatment of people with FTD-GRN.

PTV:PGRN is engineered to bind transferrin receptor molecules, which are present in large amounts on endothelial cells of the BBB and normally function to transport iron into the brain. This approach enables PTV:PGRN to be actively transported into the brain, potentially overcoming a long-standing challenge to the field of delivering protein therapeutics across the BBB.

New insights on the role of progranulin and effects of PTV:PGRN in preclinical models of FTD

Mutations in theGRNgene, which encodes the progranulin protein,generally result in reduced protein levels of progranulin and are amongst the most common genetic causes of FTD. The studies published in Cell used two common models of FTD-GRN, genetically engineered progranulin-deficient mice as well as iPSC-derived human microglial cells, to investigate the role of progranulin and effects of PTV:PGRN treatment on disease pathology.

The preclinical research showed that lysosomes which function as the digestive system of cells are the primary cellular organelles impacted by progranulin deficiency. A new finding revealed in the preclinical studies was that progranulin regulates lysosomal function through binding to and stabilizing a lysosome-specific lipid, bis(monoacylglycero)phosphate (BMP), which is critical for normal lysosomal function.

In the progranulin-deficient mice, BMP lipid levels were profoundly decreased, which resulted in reduced activity of the lipid-metabolizing enzyme glucocerebrosidase (GCase) and accumulation of the GCase substrate glucosylsphingosine (GlcSph); GCase is known to be involved in Gaucher disease and GBA-linked Parkinsons disease. A mild decrease in BMP and an increase in GlcSph was also found in biofluid samples from patients with FTD, with or without GRN mutations.

Treatment of progranulin-deficient mice or human cells with PTV:PGRN was sufficient to rescue a range of lysosomal defects, including BMP deficiency, GlcSph accumulation, lysosomal vacuolization and lysosomal membrane damage. In addition, PTV:PGRN corrected lipofuscinosis, microgliosis and astrogliosis, which are common disease-relevant brain pathologies in progranulin-deficient mice that are also present in patients with FTD-GRN.

Collectively, these new insights from our preclinical research suggest that FTD-GRN may be an atypical lysosomal storage disorder, and that lysosomal function can be restored by PTV:PGRN, said Dr. Lewcock. Our work also identified candidate clinical biomarkers indicative of lysosomal dysfunction, such as BMP and GlcSph, which may help to evaluate the future therapeutic efficacy of PTV:PGRN and other therapeutics in people with FTD-GRN.

Publication of this research in Cell marks a significant milestone in the development of therapeutics enabled by our Transport Vehicle technology, said Denalis Chief Executive Officer Ryan Watts, Ph.D. We are making great progress towards our goal of initiating clinical testing of our lead PTV:PGRN molecule (DNL593) and believe that our unique brain-penetrant progranulin replacement approach has the potential to make a difference for individuals and their families affected by FTD-GRN.

About Denalis TV Platform

The BBB is essential in maintaining the brains microenvironment and protecting it from harmful substances and pathogens circulating in the bloodstream. Historically, the BBB has posed significant challenges to drug development for CNS diseases by preventing most drugs from reaching the brain in therapeutically relevant concentrations. Denalis Transport Vehicle (TV) platform is a proprietary technology designed to effectively deliver large therapeutic molecules such as antibodies, enzymes, proteins, and oligonucleotides across the BBB after intravenous administration. The TV technology is based on engineered Fc fragments that bind to specific natural transport receptors, such as transferrin receptor, which are expressed at the BBB and deliver TV and its therapeutic cargo to the brain through receptor-mediated transcytosis. In animal models, antibodies and enzymes engineered to the TV technology demonstrate more than 10- to 30-fold greater brain exposure than similar antibodies and enzymes without this technology. Improved exposure and broad distribution in the brain may increase therapeutic efficacy by enabling widespread achievement of therapeutically relevant concentrations of product candidates.

About Denali Therapeutics

Denali Therapeutics is a biopharmaceutical company developing a broad portfolio of product candidates engineered to cross the blood-brain barrier (BBB) for neurodegenerative diseases. Denali pursues new treatments by rigorously assessing genetically validated targets, engineering delivery across the BBB and guiding development through biomarkers that demonstrate target and pathway engagement. Denali is based in South San Francisco. For additional information, please visit http://www.denalitherapeutics.com.

Cautionary Note Regarding Forward-Looking Statements

This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements expressed or implied in this press release include, but are not limited to, statements regarding Denali's plans, timelines and expectations related to PTV:PGRN, plans regarding planned future clinical studies of PTV:PGRN (DNL593), expectations regarding Denalis TV technology platform, the therapeutic potential of PTV:PGRN (DNL593) and Denalis TV platform, and statements made by Denalis Chief Scientific Officer and Chief Executive Officer. Actual results are subject to risks and uncertainties and may differ materially from those indicated by these forward-looking statements as a result of these risks and uncertainties, including but not limited to, risks related to: Denalis early stages of clinical drug development; Denalis and its partners ability to complete the development and, if approved, commercialization of PTV:PGRN (DNL593); Denalis and its partners ability to enroll patients in its ongoing and future clinical trials; Denalis reliance on third parties for the manufacture and supply of its product candidates for clinical trials; the potential for clinical trial results of PTV:PGRN (DNL593) to differ from preclinical or expected results, the risk that results from early preclinical biomarker studies will not translate to clinical benefit in clinical studies; and that PTV:PGRN (DNL593) may not receive regulatory approval as a treatment of FTD-GRN necessary to be commercialized. In light of these risks, uncertainties and assumptions, the forward-looking statements in this press release are inherently uncertain and may not occur, and actual results could differ materially and adversely from those anticipated or implied in the forward-looking statements. Accordingly, you should not rely upon forward-looking statements as predictions of future events. Information regarding additional risks and uncertainties may be found in Denalis Annual and Quarterly Reports on Forms 10-K and 10-Q filed with the Securities and Exchange Commission (SEC) on February 26, 2021, and August 4, 2021, respectively, and Denalis future reports to be filed with the SEC. Denali does not undertake any obligation to update or revise any forward-looking statements, to conform these statements to actual results or to make changes in Denalis expectations, except as required by law.

Investor Relations Contact:Laura Hansen, Ph.D.Vice President, Investor Relations(650) 452-2747hansen@dnli.com

Media Contacts:Lizzie Hyland(646) 495-2706Lizzie.Hyland@FGH.comorMorgan Warners(202) 295-0124Morgan.Warners@FGH.com

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Denali Therapeutics Announces Publication in Cell on New - GlobeNewswire

Bone Therapeutics provides update on the progress of clinical studies – Yahoo Finance

Posted: July 19, 2021 at 1:53 am


JTA-004 Phase III top-line results planned first half September

ALLOB Phase IIb currently on track but recruitment slow due to COVID-19 pandemic

Gosselies, Belgium, 19 July 2021, 7am CEST BONE THERAPEUTICS (Euronext Brussels and Paris: BOTHE), the cell therapy company addressing unmet medical needs in orthopedics and other diseases, today provides an update on its two leading ongoing clinical studies.

These studies are the pivotal Phase III clinical trial with Bone Therapeutics enhanced viscosupplement, JTA-004, targeting osteoarthritic knee pain, and the Phase IIb study with its allogeneic cell therapy product, ALLOB, in patients with difficult-to-heal tibial fractures.

The JTA-004 Phase III clinical study, having achieved target patient recruitment in December 2020, has now completed the six-month follow-up in all patients. Bone Therapeutics expects to report topline results for the 3-month primary endpoint and 6-month follow-up data in the first half of September 2021.

The Phase IIb ALLOB clinical study in high-risk tibial fractures is currently experiencing a delay in patient recruitment due to the COVID-19 pandemic and the associated containment measures. This delay is as a result of fewer accidents and reduced availability of health care facilities in the first half of 2021. Bone Therapeutics has instituted corrective measures to mitigate the impact of the pandemic on recruitment for the trial, in collaboration with its clinical research organization. At this point, Bone Therapeutics does not expect the pandemic delay in recruitment rate to have a material effect on the anticipated completion of recruitment in H1 2022. As a result, Bone Therapeutics still currently expects to deliver top line results in H2 2022 as planned. Should the pandemic continue, Bone Therapeutics may have to re-evaluate these timelines and, in that eventuality, will communicate again to the markets.

The JTA-004 Phase III study is a controlled, randomized, double-blind trial. It is evaluating the potential of a single, intra-articular injection of JTA-004 to reduce osteoarthritic pain in the knee up to 12 months, compared to placebo or Hylan G-F 20, the leading osteoarthritis treatment on the market. The study is being conducted in 22 centers across six European countries as well as Hong Kong. More than 700 patients have been treated. These patients fulfill all the strict protocol criteria including mild to moderate symptomatic knee osteoarthritis.

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ALLOB is currently being evaluated in a randomized, double-blind, placebo-controlled Phase IIb study in patients with high-risk tibial fractures. This study will assess and compare against placebo, in association with standard of care stabilization surgery, the potential for ALLOB to accelerate fracture healing after 3-months follow-up and prevent late-stage complications in these patients, after a follow-up period of 6 months. ALLOB will be applied by a single percutaneous injection 24-96 hours post-definitive reduction surgery in patients with fresh tibial fractures at risk of delayed or non-union. Following the approval in seven European countries, the study is now in the process of enrolling 178 patients in over 40 sites.

About JTA-004

JTA-004 is Bone Therapeutics next generation of intra-articular injectable for the treatment of osteoarthritic pain in the knee, a highly prevalent joint condition affecting an estimated 250 million patients worldwide. It consists of a unique mix of hyaluronic acid - a natural component of knee synovial fluid, plasma proteins, and a fast-acting analgesic. JTA-004 intends to provide added lubrication and protection to the cartilage of the arthritic joint and to alleviate osteoarthritic pain. In a previous randomized, double-blind Phase II study involving 164 patients, JTA-004 showed superior clinical benefit with an improved pain relief at 3 and 6 months compared to Hylan G-F 20, the global market leader in osteoarthritis treatment.


ALLOB is Bone Therapeutics off-the-shelf allogeneic cell therapy platform consisting of human allogeneic bone-forming cells derived from cultured bone marrow mesenchymal stromal cells (MSC) from healthy adult donors. To address critical factors for the development and commercialization of cell therapy products, Bone Therapeutics has established a proprietary, optimized production process that improves consistency, scalability, cost effectiveness and ease of use of ALLOB. This optimized production process significantly increases the production yield, generating thousands of doses per bone marrow donation. Additionally, the final ALLOB product is cryopreserved, enabling easy shipment and the capability to be stored at the point of care for easy clinical use. The process will therefore substantially improve product quality, reduce overall production costs, simplify supply chain logistics, increase patient accessibility and facilitate global commercialization. The Company has implemented the optimized production process to produce clinical batches for the ongoing Phase IIb clinical trial in patients with difficult-to-heal tibial fractures.

About Bone Therapeutics

Bone Therapeutics is a leading biotech company focused on the development of innovative products to address high unmet needs in orthopedics and other diseases. The Company has a, diversified portfolio of cell and biologic therapies at different stages ranging from pre-clinical programs in immunomodulation to mid-to-late stage clinical development for orthopedic conditions, targeting markets with large unmet medical needs and limited innovation.

Bone Therapeutics is developing an off-the-shelf next-generation improved viscosupplement, JTA-004, which is currently in Phase III development for the treatment of pain in knee osteoarthritis. Consisting of a unique combination of plasma proteins, hyaluronic acid - a natural component of knee synovial fluid, and a fast-acting analgesic, JTA-004 intends to provide added lubrication and protection to the cartilage of the arthritic joint and to alleviate osteoarthritic pain and inflammation. Positive Phase IIb efficacy results in patients with knee osteoarthritis showed a statistically significant improvement in pain relief compared to a leading viscosupplement.

Bone Therapeutics core technology is based on its cutting-edge allogeneic cell therapy platform with differentiated bone marrow sourced Mesenchymal Stromal Cells (MSCs) which can be stored at the point of use in the hospital. Currently in pre-clinical development, BT-20, the most recent product candidate from this technology, targets inflammatory conditions, while the leading investigational medicinal product, ALLOB, represents a unique, proprietary approach to bone regeneration, which turns undifferentiated stromal cells from healthy donors into bone-forming cells. These cells are produced via the Bone Therapeutics scalable manufacturing process. Following the CTA approval by regulatory authorities in Europe, the Company has initiated patient recruitment for the Phase IIb clinical trial with ALLOB in patients with difficult tibial fractures, using its optimized production process. ALLOB continues to be evaluated for other orthopedic indications including spinal fusion, osteotomy, maxillofacial and dental.

Bone Therapeutics cell therapy products are manufactured to the highest GMP (Good Manufacturing Practices) standards and are protected by a broad IP (Intellectual Property) portfolio covering ten patent families as well as knowhow. The Company is based in the BioPark in Gosselies, Belgium. Further information is available at http://www.bonetherapeutics.com.

For further information, please contact:

Bone Therapeutics SAMiguel Forte, MD, PhD, Chief Executive OfficerJean-Luc Vandebroek, Chief Financial OfficerTel: +32 (0)71 12 10 00investorrelations@bonetherapeutics.com

For Belgian Media and Investor Enquiries:BepublicCatherine HaquenneTel: +32 (0)497 75 63 56catherine@bepublic.be

International Media Enquiries:Image Box CommunicationsNeil Hunter / Michelle BoxallTel: +44 (0)20 8943 4685neil.hunter@ibcomms.agency / michelle@ibcomms.agency

For French Media and Investor Enquiries:NewCap Investor Relations & Financial CommunicationsPierre Laurent, Louis-Victor Delouvrier and Arthur RouillTel: +33 (0)1 44 71 94 94bone@newcap.eu

Certain statements, beliefs and opinions in this press release are forward-looking, which reflect the Company or, as appropriate, the Company directors current expectations and projections about future events. By their nature, forward-looking statements involve a number of risks, uncertainties and assumptions that could cause actual results or events to differ materially from those expressed or implied by the forward-looking statements. These risks, uncertainties and assumptions could adversely affect the outcome and financial effects of the plans and events described herein. A multitude of factors including, but not limited to, changes in demand, competition and technology, can cause actual events, performance or results to differ significantly from any anticipated development. Forward looking statements contained in this press release regarding past trends or activities should not be taken as a representation that such trends or activities will continue in the future. As a result, the Company expressly disclaims any obligation or undertaking to release any update or revisions to any forward-looking statements in this press release as a result of any change in expectations or any change in events, conditions, assumptions or circumstances on which these forward-looking statements are based. Neither the Company nor its advisers or representatives nor any of its subsidiary undertakings or any such persons officers or employees guarantees that the assumptions underlying such forward-looking statements are free from errors nor does either accept any responsibility for the future accuracy of the forward-looking statements contained in this press release or the actual occurrence of the forecasted developments. You should not place undue reliance on forward-looking statements, which speak only as of the date of this press release.

Originally posted here:
Bone Therapeutics provides update on the progress of clinical studies - Yahoo Finance

Biological functions and clinical studies of FGF21 | DMSO – Dove Medical Press

Posted: at 1:53 am


Fibroblast growth factors (FGFs) are widely expressed in the human body and have numerous and complicated physiological functions. FGFs regulate cell growth, proliferation, differentiation, and metabolic modulation, tissue repair, and inflammatory response.1,2 FGFs can be divided into three types (classic, intracellular and hormone-like types) based on their action modes.3 Classic and intracellular FGFs mostly act in an autocrine or paracrine way,4 while hormone-like FGFs mainly act in the endocrine way.5 Most autocrine and paracrine FGFs have a high affinity for the heparin glucosamine sulfate (HSGAG), which promotes the binding of the FGFs to the tyrosine kinase FGF receptor (FGFR1-4) on the cell surface, inducing FGFR activation, dimerization, and activation of downstream signaling pathways.69 HSGAGs can also stabilize FGFs, prevent FGFs degradation, and limit the diffusion range of FGFs.10

FGF21 is a member of the FGF19 subfamily in the FGFs family and belongs to the hormone-like FGFs. Compared to other FGFs members, FGF21 has three special features: 1. It has no obvious mitogenic or tumor-promoting function;11 2. The spatial configuration variation of the region that binds to HSGAGs makes it have a weaker affinity for HSGAG, thus not easily bound in the extracellular matrix. However, it enters the circulation in the form of endocrine hormones to regulate metabolism and cross the blood-brain barrier through simple diffusion;12 3. It does not directly bind to cell receptors, and it needs -Klotho protein to form a stable combination to play its physiological role. Herein, the latest research progress on FGF21 is summarized.

Unlike the classical FGFs, FGF21 binds to FGF receptors (FGFRs) and the co-receptor protein -Klotho (a single transmembrane protein expressed during the differentiation of adipose precursor cells into adipocytes). Besides, FGF21 activates the signal transduction downstream only when FGFRs and -Klotho are dimerized and autophosphorylated.13,14 Neither -Klotho nor FGFRs can be activated by FGF21 alone.15 In the FGF21-FGFRs--Klotho complex, -Klotho, a zip code-like receptor, is the main high-affinity receptor of FGF21, providing the targeted signals for FGF21. At the same time, FGFR acts as a catalytic subunit that mediates receptor dimerization and intracellular signal transduction.16 Studies have also shown that the C-terminus and N-terminus are involved in activating FGF21 receptors, and any deletion of the terminus greatly reduces FGF21 activity. The C-terminus of FGF21 has a sugar-mimicking Ser-pro-Ser motif, which can be recognized and bound by -Klotho. Besides, the C-terminus mutation of FGF21 is associated with an affinity decrease of -Klotho, indicating that the C-terminal also mediates the binding of FGF21 and -Klotho. Although the N-terminal mutation of FGF21 is also associated with decreased activity, it can still bind to -Klotho, suggesting that the N-terminal only participates in the receptor activation process.1619 Therefore, complete C-terminal and N-terminal structure and simultaneous binding to -Klotho and FGFRs promote the physiological functions of FGF21.

Studies have shown that FGF21 is highly expressed in the liver, skeletal muscle, kidney, heart, fat, and blood vessels.20 FGF21 (mainly produced by liver cells) is also expressed in the blood circulation due to its hormone-like characteristics,21 targeting the heart, bones, kidneys, small intestine, and brain because of its strong diffusion and distribution ability.13 However, FGF21 produced in adipose tissue most acts in an autocrine or paracrine manner on the metabolic regulation of itself and adjacent tissues.22 Moreover, the expression level of FGF21 varies greatly in different tissues and under different conditions. FGF21 expression level can be regulated in the following ways;

Numerous transcription regulators can also regulate the FGF21 expression level. For instance, peroxisome proliferator-activated receptor (PPAR) can regulate FGF21 expression by binding to the transcriptional regulatory element at the beginning of the FGF21 promoter region, and FGF21 and PPAR can regulate each other. PPAR contains three subtypes: PPAR, PPAR/, and PPAR. PPAR and PPAR can induce FGF21 expression. PPAR can induce FGF21 expression in the liver,23 and FGF21 level in the liver of mice was significantly increased after the administration of PPAR agonist fenofibrate, indicating the effect of PPAR on promoting FGF21 expression. Similarly, PPAR can regulate the expression and function of FGF21 in adipose tissue. Muise et al24 found that the PPAR agonist rosiglitazone can activate PPAR, promoting fat cells to produce FGF21 and synergistically regulating FGF21 to accelerate glucose uptake and utilization. Conversely, FGF21 in the tissue can also activate PPAR and PPAR . Dutchak et al25 indicated that FGF21 induced by PPAR in adipose tissue can increase its transcription by inhibiting PPAR ubiquitination. These processes form a cyclic loop of PPAR, PPAR, and FGF21 and feed-forward to regulate FGF21 expression.

Recent studies have indicated that microRNAs (miRNAs) are associated with the regulation of metabolism and metabolic disorders.26 MiRNAs primarily bind to the 3-untranslated region (3UTR) of mRNAs, inhibiting mRNAs translation and regulating the expression of related genes. The activity of the 3UTR of FGF21 mRNA in the liver can be inhibited by circulating exosomal miRNAs, in which miR-99b is the identified regulatory factor.27 Furthermore, anti-miR-577 therapy can protect and restore the insulin regulation of FGF21 and improve the survival and function of diabetic pancreatic -cells.28,29 MiR-212 can inhibit FGF21 expression in HepG2 cells in non-alcoholic fatty liver disease (NAFLD), while miR-212 inhibitors can increase FGF21 protein level and reduce lipid synthesis. Si-FGF-21 silences the expression of FGF21, significantly increasing the lipid content in HepG2 cells, thus hindering the anti-lipid effect of miR-212 inhibitors in these cells.30 Collectively, these suggest that miR-212 targets FGF21, thus regulating FGF21 expression.

Fasting, ketogenic diet, high-sugar diet, and high-fat diet are all important transcription inducers for FGF21 expression. Fasting can strongly induce FGF21 expression.31 A ketogenic diet or fasting can significantly increase FGF21 expression by recruiting PPAR in the region near the FGF21 transcriptional promoter.23,32 Notably, neither the ketogenic diet (up to 3 months) nor short-term fasting (up to 48 hours) can increase serum FGF21 levels in humans.23 However, prolonged fasting (710 days) can increase serum FGF21 levels in humans, possibly due to the different metabolic rates and fasting tolerances among different species.33 A high-fat diet induces excessive unsaturated fatty acids and bile acids, increasing the transcription and secretion of FGF21 in the liver by activating the farnesoid X receptor (FXR) and PPAR.34 Lundsgaard et al35 found that a high-carbohydrate diet can also induce FGF21 gene expression in the liver.

FGF21 can also be highly expressed under oxidative stress, energy stress, endoplasmic reticulum stress, cold stress, and mitochondrial dysfunction, and its expression is also regulated by sodium butyrate, metformin, glucocorticoids, etc.3638 Animal studies have shown that one-time acute exercise (60 minutes on a treadmill or until repeated electrical stimulation rendered normal running impossible) promotes gene expression in the liver of mice and increases serum levels of FGF21. Clinical trials have also shown that 30 minutes of acute aerobic exercise can also increase circulating FGF21 levels.39 FGF21 expression level in skeletal muscle is very low in healthy conditions, and circulating FGF21 mainly comes from the liver. However, the expression of myogenic FGF21 significantly increases in some stress states, such as hunger, endoplasmic reticulum stress, mitochondrial dysfunction, etc.40,41 Kim et al42 found that the FGF21 content significantly increased in the soleus muscle of Zucker diabetic obese rats after 12 weeks of resistance exercise. However, the phenomenon was not observed in the gastrocnemius muscle.

Earlier research on FGF21 function mainly focused on reducing blood sugar and lipids, lowering body weight, improving insulin resistance (IR), and cardiovascular diseases related to abnormal glucose and lipid metabolism, such as coronary heart disease, heart remodeling.12,43 In recent years, the functions of FGF21 in inhibiting inflammation, reducing oxidative stress levels,44,45 and inhibiting apoptosis of endothelial cells46 and cardiomyocytes47 have been studied. The regulatory effects of FGF21 on metabolic diseases, such as obesity, hyperlipidemia, and hyperglycemia, the damage repair effects on inflammation and apoptosis, and the blocking effects on some cancers indicate that FGF21 has a broad prospect for development. Studies have shown that FGF21 mainly participates in the processes of material metabolism, heart and brain damage by activating Adenosine 5-monophosphate (AMP)-activated protein kinase (AMPK), serine/threonine protein kinase (Akt), and extracellular-regulated protein kinases (ERK) and other downstream factors. FGF21 plays metabolic regulation functions, such as promoting glucose uptake, gluconeogenesis, increasing the oxidation of free fatty acids, promoting ketogenesis, increasing energy production and utilization.48,49 FGF21 also has the effect of apoptosis protection and neurocognitive function recovery.

Insulin, as one of the most important humoral factors regulating glucose metabolism, enhances glucose absorption by activating the Phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway and promoting the expression of glucose transporter 4 (GLUT4).50 FGF21 can also activate the PI3K signaling pathway and regulate Akt activation. However, FGF21 mainly inhibits the expression of related gluconeogenesis and glucose production by inducing phosphorylation of atypical protein kinase C (PKC) I/L and exerts insulin-like hypoglycemic effect to control blood glucose balance.51 Ge et al52 found that glucose transporter-1 (GLUT1) promoter is highly conserved in serum response element (SRE) and E-26 (ETS) binding motifs. FGF21 binds to the receptor to activate the downstream factor extracellular signal-regulated kinases (ERK1/2)), and then activate ETS-like protein-1 (ELK-1) and serum response factor (SRF, the downstream target of ERK1/2), enhancing glucose uptake and reducing blood glucose concentration by combining the promoter sequence of GLUT1 gene, trans-activating GLUT1 gene and inducing GLUT1 expression. Furthermore, there can be a synergistic effect between insulin and FGF21. Insulin can activate PKC, enhancing the FGF21 regulation effect on the GLUT1 expression through the ERK1/2-SRF/Elk-1 pathway.53 FGF21 can also improve insulin sensitivity and enhance the hypoglycemic effect of insulin. The mammalian target of rapamycin complex 1 (mTORC1) and its downstream effector, ribosomal protein S6 kinase 1 (S6K1), are the key regulators of nutritional overload-induced insulin resistance and the pathogenesis of type 2 diabetes mellitus (T2DM).54 S6K1 phosphorylates insulin receptor substrate 1 (IRS-1), thereby destroying PI3K, a key molecular basis for inducing IR. FGF21 binds to the receptor complex, downregulating mTORC1 in a tuberous sclerosis complex (TSC)-dependent manner, thus activating downstream pathways to improve insulin resistance and increase insulin sensitivity.55 Notably, FGF21 has a two-way regulatory role in lowering and raising blood sugar levels. Besides, animal experiments and clinical trials have shown different functions of FGF21 and the body regulation mechanism of normal and abnormal metabolism.

Rat experiments showed FGF21 improves IR, increases insulin sensitivity, and reduces blood insulin concentration.12 FGF21 analogues also improve IR, reduces blood glucose and insulin levels, and improve glucose tolerance in primates.56 Moreover, scholars have discovered that adipose tissue is a key target of FGF21 for glucose metabolism regulation, and a certain amount of adipose tissue in mice is the guarantee for FGF21 to regulate blood sugar.57 Clinical trials have shown that FGF21 analogues (LY2405319, PF-05231023, BMS-986036, etc.) also lower blood glucose. However, their effect on lowering blood glucose was not significant.17,58,59 Further studies have shown that FGF21 also promotes gluconeogenesis and maintains blood glucose balance, preventing hypoglycemia occurrence.12

FGF21 reduces blood glucose by promoting the phosphorylation of Akt via insulin, thereby upregulating the number of insulin receptors, increasing insulin sensitivity, and alleviating chronic inflammatory response, thus improving IR, thus regulating glucose metabolism.6062 Second, FGF21 can upregulate adiponectin expression in adipocytes by activating the PPAR signaling pathway to promote GLUT4 migration from cytoplasm to cell membrane, or directly promoting GLUT1 expression, increasing glucose transport and lowering blood glucose.22,63,64 FGF21 can also act on pancreatic islets and indirectly induce a hypoglycemic effect. FGF21 can inhibit islet cells to reduce glucagon secretion,12 inhibiting the synergistic toxicity of glycolipid and cytokine-induced cell apoptosis, reducing the damage of islet cells and enhancing the function of islet cells, thereby improving blood sugar level.65

In terms of gluconeogenesis, studies have shown that FGF21 can increase and maintain blood sugar under fasting or starvation.66 FGF21 secreted by tissue cells can cross the blood-brain barrier and directly act on the hypothalamus through the hypothalamic-pituitary-adrenal axis, stimulating the synthesis and release of adrenal corticosterone increasing blood glucose via liver gluconeogenesis.67 Furthermore, FGF21 can bind to FGFRs in the liver to activate the downstream RAS-RAF-MAPK signaling pathway via the -Klotho, resulting in a cascade reaction. FGF21 then induces the expression of early liver genes, such as PPAR coactivator-activated receptor- coactivator 1 (PGC1) gene, which increases the transcriptional activity of PPAR. It upregulates the expression of gluconeogenesis-related genes, thereby regulating gluconeogenesis.68,69

FGF21 is an adipokine, which regulates blood lipid. It can significantly reduce the plasma levels of total cholesterol (TC), low-density lipoprotein (LDL), and triglyceride (TG) and increase the plasma levels of high-density lipoprotein (HDL) and adiponectin in normal subjects.70 A study indicated that diet-induced obese mice and hereditary db/db obese mice have weight loss, reversal of liver steatosis, and reduction in plasma TG levels changes after several weeks of continuous FGF21 administration. Plasma TC and LDL levels decrease, while HDL level increases in a dose-dependent manner in mice administered with different FGF21 doses.71,72 Similar findings were found in diabetic monkeys. Besides the decrease in blood glucose to the normal level, the decrease of blood insulin level, and the enhancement of the bodys sensitivity to insulin, blood lipid also decreased, especially the selective decrease of TG and LDL. At the same time, HDL showed an upward trend after long-term injection of FGF21 in diabetic monkeys.73

FGF21 also plays an important role in liver fat metabolism. Liu et al74 indicated that long-term alcohol exposure induces liver damage and steatosis, inducing the body to upregulate FGF21 as compensation. Knockout of the FGF21 gene inhibits -oxidation of liver fatty acids, aggravating alcoholic steatohepatitis (ASH). However, recombinant FGF21 alleviates liver steatosis and inflammation induced by ASH. Furthermore, the treatment of rodent and non-human primate model animals of NAFLD, FGF21 analog, and B1344 showed an inhibited liver inflammation and natural immune cell infiltration, reduced liver injury and hepatocyte death, significantly improved liver lipid accumulation, liver fibrosis, and prevented further development of non-alcoholic steatohepatitis (NASH).75 However, B1344 has greater potency, higher maximum response, and lower immunogenicity than FGF21.

Humans and animals have white adipose tissue (WAT) and brown adipose tissue (BAT). The WAT mainly stores metabolic surplus energy in the form of TG, which causes weight gain.76 Unlike WAT, BAT is rich in multi-crystal mitochondria, which is the main source of non-shivering thermogenesis. BAT maintains the body temperature and energy balance by increasing the uptake of glycolipids and using uncoupling protein 1 (UCP1) to decouple biological oxidation from ATP synthesis, thus converting energy released via biological oxidation into heat, reducing ATP synthesis.77,78 FGF21 can upregulate the expression of UCP1 and other thermogenesis genes, promoting the Browning of WAT, thus regulating the balance between body temperature and energy.79 However, scholars have also found that FGF21 regulates energy metabolism only in mice with abnormal metabolism.79,80 Furthermore, Liver kinase B1 (LKB1) phosphorylation activates AMPK, thereby increasing the content of NAD+ in cells, activating Sirtuin 1 (SIRT1), thus promoting mitochondrial energy transformation in skeletal muscles.8183 FGF21 in skeletal muscle is also transported to adipose tissue through blood circulation, increasing the level of FGF21 in WAT and further inducing the expression of silent mating type information regulation 2 homolog 1 (SIRT1), PGC1 , UCP1 and other factors, thus promoting the Browning of WAT and increasing energy consumption.84 Collectively, the above studies indicate that FGF21 maintains the energy balance of the body with abnormal metabolism through the regulation of glucose and lipid metabolism, which does not affect the normal metabolism in the body.

Recent studies have shown that FGF21 has an important protective effect on the heart, reflected by reducing myocardial cell apoptosis, antagonism against ischemia-reperfusion injury (IRI), and oxidative stress reaction. Roberts et al85 and Cong et al86 showed that FGF21 could inhibit the activity of the apoptotic factor C-caspase 3 through the PI3K /Akt signaling pathway, increase cardiac energy supply through the AMPK pathway, thus inhibiting the apoptosis of cardiomyocytes. Moreover, FGF21 interferes with the PER K-eIF2-ATF4-CHOP signaling axis during endoplasmic reticulum stress, activating the ATF4 signaling pathway and promoting the phosphorylation of c-Jun N-terminal kinase (JNK), thus reducing the accumulation of abnormally folded proteins and inhibiting myocardial cell apoptosis.87 FGF21 can also effectively prevent palmitate-induced cardiac apoptosis by upregulating the ERK1/2-dependent p38 mitogen-activated protein kinase (MAPK)-AMPK signaling pathway88 and reduce cardiomyocyte IRI and apoptosis after oxidative stress through PI3K/AKT-dependent pathways. 1. FGF21, as an antioxidant factor, induces the expression of antioxidant genes, such as Ucp3, Ucp2, and Sod2 in the heart, thereby preventing the production of reactive oxygen species (ROS).89 2. FGF21 can also activate MAPK to produce a cascade reaction by binding FGFR1c/-klotho. Therefore, FGF21 can promote the activation of AMPK, the target gene of Liver kinase B1 (LKB1), and reduce the accumulation of ROS, inhibiting apoptosis.89 3. FGF21 promotes transcriptional activation of PPAR by regulating PPAR coactivator 1, thus controlling energy metabolism and oxidative stress in multiple tissues,90 inducing a protective role on cardiac hypertrophy.

Although it is unknown whether the brain can directly generate FGF21, it has been proved that FGF21 can move to the brain through the blood-brain barrier via simple diffusion,91,92 playing a key role in metabolic regulation, neuroprotection, and the potential role of cognition.

FGF21 can bind to FGFRs and -klotho expressed in the hypothalamus, the suprachiasmatic nucleus (SCN), paraventricular nucleus of the hypothalamus (PVN), and other regions of the brain, and act on the Hypothalamus-pituitary-adrenal axis (HPA) and hypothalamic-pituitary-gonad axis (HPG) to regulate the levels of corticotropin-releasing hormone (CRH) and vasopressin (AVP). The increased release of CRH can promote the substantial release of adrenal cortex hormones, which combine with the liver to induce PGC1 expression. Therefore, FGF21 can upregulate the expression of gluconeogenesis genes, such as glucose 6 phosphatase and phosphoenolpyruvate carboxykinase via PGC1, increasing liver gluconeogenesis and preventing hypoglycemia.67 Moreover, increased CRH in the circulation can increase sympathetic nerve activity in BAT, upregulate UCP1 expression and increase lipolysis in BAT, leading to an increase in energy use and a decrease in weight gain in diet-induced obese mouse models.93 The inhibited release of AVP decreases kisspeptin in the hypothalamus, causing a decrease in the release of luteinizing hormone, affecting ovulation and fertility.94

Several studies have shown that FGF21 has an important protective effect on nerve injury and cognitive impairment. Shahror et al95 showed that FGF21 can significantly improve the spatial memory deficits, hippocampal nerve damage, and dendritic morphology abnormalities induced by traumatic brain injuries (TBI). Therefore, FGF21 alleviates TBI-induced defects in neurogenesis and maturation of immature hippocampal neurons, thereby restoring the hippocampal independent learning and memory impairment caused by TBI. Sa-Nguanmoo et al96 also confirmed that FGF21 enhances hippocampal synaptic plasticity, increases the density of dendritic spines, restoring the function of brain mitochondria. FGF21 can prevent defective neuroprotective molecules in astrocytes, alleviating memory dysfunction and neurodegeneration, such as amyloid plaque pathology and pathological Tau hyperphosphorylation, thus acting as a neuroprotective agent in Alzheimers disease (AD).97,98 FGF21 can also protect the blood-brain barrier after ischemic stroke by activating PPAR in cerebral blood vessels,99 antagonize the M1 polarization of microglia and the accumulation of pro-inflammatory cytokines by inhibiting NF-B and upregulating PPAR, and reduce cerebral edema and inflammation after TBI and stroke.100,101

The level of FGF21 in normal human circulation is low, while it is significantly increased in patients with atherosclerosis, hypertension, and liver disease.102104 Some scholars have also indicated that FGF21 levels in obese or hyperlipidemia patients are 1.52 times higher than in normal people. Patients with renal insufficiency may also accumulate FGF21, while FGF21 levels in patients with long-term malnutrition (such as patients with anorexia nervosa) are low.105107 FGF21 expression is decreased in patients with type 1 diabetes mellitus (T1DM) and increased in patients with T2DM in individuals with abnormal glucose metabolism, indicating that FGF21 resistance or compensatory increase may exist in patients with T2DM.108 Similarly, FGF21 up-regulation occurs in patients with metabolic syndrome,109 possibly because FGF21 plays a compensatory role in the early stage of the disease, promoting the occurrence and development of the disease. Li et al110 found that the plasma FGF21 content and liver FGF21 levels are significantly higher in NAFLD patients than in healthy people. Therefore, FGF21 may be a new biomarker for NAFLD diagnosis. Taken together, these findings indicate that FGF21 has broad prospects as a serum marker in the prevention, diagnosis, treatment, and efficacy evaluation of metabolic abnormalities. Presently, FGF21 has been partially used in clinical practice.

The routine auxiliary examination items, such as serum lactic acid, alanine, creatine kinase have low specificity and sensitivity during the diagnosis of mitochondrial diseases. Recent studies have shown that serum levels of FGF21 are elevated when mitochondrial DNA mutations occur in skeletal muscle but not when similar mutations occur in other organs. Therefore, serum FGF21 is a relatively good biomarker for muscle mitochondrial diseases than other indicators.111

Serum FG21 can also be used for early disease detection. For instance, the incidence rate of myocardial ischemia, cardiac hypertrophy, and diabetic cardiomyopathy is positively correlated with serum FGF21 levels.112114 Some studies have also indicated that higher serum FGF21 levels are associated with a higher risk of coronary heart disease, NAFLD, and T2DM.89,115117 Besides, higher circulating FGF21 levels are associated with higher mortality in patients with end-stage renal disease.110 However, animal experiments and clinical trials have shown different results. Therefore, further studies are necessary to determine whether FGF21 can be used as a molecular marker for the early diagnosis and evaluation of related diseases.

FGF21 also has important clinical significance for disease treatment. Animal experiments have shown that the metabolic phenotypes, such as decreased blood glucose, serum TC and TG levels, increased insulin sensitivity and glucose uptake of two groups of mice overexpressing human and mouse FGF21 are highly similar. However, there are also some differences. For instance, the weight and body fat rate of mice overexpressing human FGF21 decreased, while those overexpressing mouse FGF21 were obese and unresponsive despite having normal metabolism.17 This study provides a basis for the clinical treatment of FGF21. Clinically, FGF21 levels are elevated in patients with various metabolic abnormalities. In contrast, the findings have shown that FGF21 effectively treats various metabolic abnormalities in animal models. However, it is speculated that the phenomenon is similar to hyperinsulinemia. The increase of FGF21 may be due to FGF21 resistance produced by the activation of its compensatory mechanism,118 indicating that the elevated FGF21 is the bodys self-protection mechanism. Therefore, FGF21 can treat metabolic disorders, such as diabetes and lipid metabolism disorders, because it does not possess the classic mitogenic activity of the FGFs.119

This article reviews the metabolic regulation, injury protection, and other physiological and pathological functions of FGF21 in various tissues and organs in the body, such as the liver, heart, brain, and adipose tissue, and related regulatory mechanisms. To date, the relevant signal pathways of FGF21 have not been fully elucidated. Therefore, an in-depth study on the systemic biological functions and regulatory pathways of FGF21 can promote the prevention and treatment of metabolic disorders, such as diabetes and obesity, and cardiac and brain diseases, such as myocardial IRI and AD, TBI, and stroke.

The authors report no conflicts of interest in this work.

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YishengBio Announces PIKA recombinant COVID-19 vaccine received Phase I clinical trial IND clearance from the UAE – Markets Insider

Posted: at 1:53 am

BEIJING, July 19, 2021 /PRNewswire/ -- YishengBio Co., Ltd("YishengBio") today announced that it has received IND clearance for PIKA recombinant COVID-19 vaccine to conduct Phase I clinical trial from United Arab Emirates Ministry of Health & Prevention. PIKA recombinant COVID-19 vaccine is a PIKA adjuvanted recombinant trimeric SARS-Cov-2 spike (S) protein subunit vaccine (CHO cells). YishengBio is a biopharmaceutical company focusing on discovery, development, manufacturing and commercialization of new generations of vaccines and therapeutic biologics in the field of infectious diseases and cancer.

Preclinical studies have demonstrated that PIKA recombinant COVID-19 vaccine is capable of inducing rapid and efficient production of neutralizing antibody and cellular immunity against the currently prevalent virus variants of SARS-CoV-2, including the variants from the United Kingdom, South Africa, Brazil and India. ThePIKA recombinant COVID-19 vaccine has achieved effective long-term protection broadlyagainst those prevalent variants even at day 406 post vaccination based on animal serum studies. In addition, PIKA recombinant COVID-19 vaccine exhibits promising therapeutic benefit in non-human primates challenge study.

Considering the evolvement of the COVID-19 pandemic around the world, YishengBio is going to initiate clinical studies and intends to seek approval to market YS-SC2-010 in multiple countries. With its universal profile against existing and emerging variants, PIKA recombinant COVID-19 vaccine has the potential to become both prophylactic and therapeutic vaccine. A state-of-art manufacturing facility is currently under construction with annual production capacity of up to one billion doses to meet the future need for mass immunization.

Mr. Yi Zhang, YishengBio's chairman and the project leader, expressed his enthusiasm saying "we are very pleased with this important milestone for PIKA recombinant COVID-19 vaccine. Since the outbreak of COVID-19, our research team has designed and optimized several recombinant protein antigen candidates and ultimately selected YS-SC2-010 antigen to move forward after rigorous screening and optimization efforts. PIKA adjuvant plays a critical role in the vaccine complex by enhancing both antibody and cellular immunity and ultimately providing broad and sustainable protective effect."

"Our proprietary PIKA adjuvant technology is based on TLR-3 agonist technology independently developed by our researchteam and has been granted over 60 patents among more than 30 countries with additional40 patents in application or review stage. PIKA technology has been used in developing a variety of new generation of vaccine candidates, such as PIKA rabies vaccine, PIKA immuno-oncology product, PIKA HBV vaccine and PIKA influenza vaccine. In addition, PIKA adjuvant technology can significantly reduce the dose of antigens used hence significantly increases vaccine production and provide vaccines to more countries and regions around the world, benefiting more people" commented by Mr. Yi Zhang.

Dr. Zhongkai Shi, chief medical officer of YishengBio shared his view saying"considering emergence of prevalent variants of concerns around the globe we would like to accelerate the clinical development plan of PIKA recombinant COVID-19 vaccine by conducting a series of clinical trials in China, Southeast Asia, the Middle East, the United States and Europe. We look forward to the desired clinical benefits and advantages of YS-SC2-010 to be demonstrated in human subjects, and the next clinical milestone of PIKA recombinant COVID-19 vaccine in the global fight against the COVID-19 pandemic."

About YishengBio

YishengBio is a fully integrated biopharmaceutical company with a global footprint that is discovering, developing and commercializing innovative biotherapeutics for infectious disease and cancer. The PIKA immunomodulating technology platform is developed in-house through which it empowered and nurtured a diverse pipeline of vaccines and therapeutic biologics with better efficacy and safety potential to address the unmet medical needs in infectious disease and cancer fields. In addition, YishengBio has a revenue generating marketed product, YSJA () rabies vaccine, which is the first aluminum-free lyophilized rabies vaccine launched in China. YishengBio's other product candidates also include PIKA rabies vaccine, PIKA recombinant COVID-19 vaccine, PIKA YS-ON-001, and PIKA YS-HBV-001, PIKA YS-HBV-002, PIKA YS-ON-002 and PIKA influenza vaccine. YishengBio is headquartered in Beijing with more than 600 employees in China, U.S., Singapore. For more information on Yisheng, please visit http://www.yishengbio.com.

About PIKA recombinant COVID-19 vaccine

PIKA recombinant COVID-19 vaccine is an innovative prophylactic and therapeutic vaccine candidate against multiple SARS-COV-2 variants.It isa PIKA adjuvanted recombinant trimeric SARS-Cov-2 spike (S) protein subunit vaccine (CHO cells). Preclinical studies have demonstrated that PIKA recombinant COVID-19 vaccine is capable of inducing rapid and efficient production of neutralizing antibody and cellular immunity against the currently prevalent virus variants of SARS-CoV-2, including the variants from the United Kingdom, South Africa, Brazil and India. ThePIKA recombinant COVID-19 vaccine has achieved effective long-term protection broadlyagainst those prevalent variants even at day 406 post vaccination based on animal serum studies, indicating good durability of the immune response. In addition, PIKA recombinant COVID-19 vaccine exhibits promising therapeutic benefit in non-human primates challenge study.

SOURCE Yisheng Biopharma Co., Ltd.

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YishengBio Announces PIKA recombinant COVID-19 vaccine received Phase I clinical trial IND clearance from the UAE - Markets Insider

Dying patients with rare diseases struggle to get experimental therapies – The Detroit News

Posted: at 1:53 am

Christina Bennett| Kaiser Health News

At 15, Autumn Fuernisen is dying. She was diagnosed at age 11 with a rare degenerative brain disorder that has no known cure or way to slow it down: juvenile-onset Huntingtons disease.

Theres lots of things that she used to be able to do just fine, said her mom, Londen Tabor, who lives with her daughter in Gillette, Wyoming. Autumns speech has become slurred and her cognitive skills slower. She needs help with many tasks, such as writing, showering and dressing, and while she can walk, her balance is off.

Autumn has been turned down for clinical trials because she is too young.

It is so frustrating to me, Tabor said. I would sell my soul to try to get any type [of treatment] to help my daughter.

For patients like Autumn with serious or immediately life-threatening conditions who do not qualify for clinical trials and have exhausted all treatment options, there may be another option: seeking approval from the Food and Drug Administration for expanded access, or compassionate use, of experimental therapies.

Definitive numbers are hard to find, but studies from researchers, actions by drugmakers and insights from experts suggest that getting expanded access to unproven therapies for rare diseases is more difficult than for more common illnesses, such as cancer.

Even with experimental treatments on the rise, patients with rare diseases frequently face an unwillingness by drug companies to provide them before clinical studies are completed. Developing drugs for these diseases is an especially fragile process because the patient populations are small and often diverse, having different genetics, symptoms and other characteristics, which makes studying the drugs effects difficult.

Drugmakers believe offering a drug before studies are finished could impair its development and jeopardize FDA approval.

Companies working on therapies for rare diseases, especially smaller ones, could feel those repercussions acutely, said Lisa Kearns, a researcher in the ethics division of New York Universitys medical school and member of the divisions working group on compassionate use and preapproval access. Theres not as much investment in rare diseases, so an [adverse] event could frighten the already limited number of potential investors.

Drugs that were not made available for compassionate use last year until studies were completed include Evrysdi, for spinal muscular atrophy; Enspryng, for an autoimmune disease of the optic nerve and spinal cord called neuromyelitis optica spectrum disorder; and Viltepso, for certain patients with Duchenne muscular dystrophy.

A spokesperson for Roche, which makes Evrysdi and Enspryng and is working on a treatment for Huntingtons disease, said the decision was tied not to the type of disease but to company policy: Roche does not set up expanded access programs for any drugs until results are available from a phase 3 clinical trial. (Those phase 3 studies are typically the last testing done before the company seeks drug approval.)

Another companys experimental drug for myasthenia gravis, an autoimmune disease that leads to skeletal muscle weakness, similarly was not available through an expanded access program until research was completed last year, and no programs have started for a therapy being studied in a phase 3 clinical trial for Huntingtons disease and for amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disease often referred to as Lou Gehrigs disease.

One slight, but notable, deviation: Drugmaker Biogen agreed this year to allow certain ALS patients to receive an experimental drug as early as July 15, after the testing was to be completed but before the results are known.

Dr. Merit Cudkowicz, a neurologist at Massachusetts General Hospital in Boston, has helped patients get therapies through expanded access. Since September 2018, she and colleagues launched 10 programs that seek to match people with ALS therapies being developed by drug companies, but only about 120 patients have received therapies this way. More than 16,000 people in the United States were estimated in 2015 to have ALS and most do not qualify for clinical trials because of the progression of their disease or very strict eligibility requirements.

These examples contrast with some drugs for more common problems. Gleevec, for leukemia, was offered to thousands of patients through expanded access programs before the manufacturer completed the clinical studies that led to FDA approval. Videx, for HIV/AIDS, and Iressa, for the most common type of lung cancer, were similarly offered to large numbers of patients even as clinical trials were ongoing.

Last year, Novartis gave more than 7,000 patients worldwide early access to cancer drugs.

Doctors also report that getting experimental drugs for cancer patients is relatively simple. More than 200 physicians around the country were surveyed, and among those who applied for access, nearly 90% said they had secured drugs still being investigated for patients who were not responding to approved therapies.

California researchers found similar trends in a review of 23 social media campaigns launched by patients between 2005 and 2015 seeking a variety of experimental treatments. While seven of the 19 patients with cancer received early access to requested drugs, no access was allowed for three patients with rare diseases, although one of those patients was allowed to enroll in a clinical trial.

Companies base their decisions on whether to provide a therapy through expanded access on a number of factors, said Jess Rabourn, CEO of WideTrial, which helps pharmaceutical companies run compassionate use programs. In general, there should be evidence that patients can tolerate the treatment and an expectation that any benefit outweighs the risk, he said.

This idea that you have to wait until the research is done is baloney, he said. Were talking about patients who are going to die if theyre told to wait.

But drugmakers often view it differently, even though evidence suggests that granting early access very rarely disrupts drug approval.

Kearns explained that companies often wait until phase 3, or after, because they can be relatively confident of a drugs safety and effectiveness. They dont want to harm patients, of course, but they also do not want to threaten the drugs eventual regulatory approval with an adverse event in [a] very sick patient population.

Melissa Hogan, who consults on clinical trials for rare diseases and is an FDA patient representative, attributes the lack of access to the high cost of therapies and the tightknit nature of the rare disease community, where patients and their families often set up social media groups and exchange ideas and treatment plans. Companies know that if one patient gains access, other patients will know and ask for access, said Hogan, who has a son with mucopolysaccharidosis type II. That could overwhelm small drugmakers with little manufacturing capacity.

These concerns cause many companies [to] just throw up their hands and take a hard line of no [expanded access] until they reach approval stage, said Hogan.

The 2018 Right to Try law offers another option for some patients. Unlike expanded access, the law applies only to requests for medicines not medical devices and does not require approval from the FDA or an institutional review board, a committee that reviews and monitors people participating in research for their protection. The legislation, however, doesnt oblige companies to grant a request.

For Cali Orsulak, expanded access may be her husbands only option. He was diagnosed with ALS in 2019 at age 43.

We did our best with the skill level we had to search clinical trials all over Canada and the U.S., and then covid hit and it became increasingly difficult, said Orsulak, explaining that they live in Canada but seek medical care in the United States. Now that my husband has progressed, its even harder to get into clinical trials.

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Dying patients with rare diseases struggle to get experimental therapies - The Detroit News

Tezepelumab as an Emerging Biologic to Treat Asthma – MD Magazine

Posted: at 1:53 am

Reynold Panettieri Jr, MD: Lets transition. The alarmin cytokines was a perfect setup. TSLP, IL-33, IL-25: these are cytokines, liberated by the epithelium after injuryvirus, toxic, allergicthat then rain down into the effector cells. I imagine that epithelial muscle interaction really doesnt need other players, because many of these receptors are found on the muscle. You could have an uncoupling of airway inflammation from asthma, or airway hyperresponsiveness or bronchoconstriction, which wasnt really recognized before. Everything was felt to be but IL-33 or TSLP can directly affect the muscle and excitation-contraction coupling [actin and myosin binding]. I dont need another immunocyte to transmit that signal. Nic, do you want to discuss tezepelumab? This is really exciting. This is a new biologic. Its not out. Its still in development, but the phase 3 trials are going on and theyre encouraging. What excites you, Nic?

Nicola Hanania, MD, MS: Everything you said excites me. This light at the end of the tunnel for these patients that we see every day keeps us going and keeps the hopes up. We talked about smooth muscles, which also is something that is of interest to me. But another very important structural set of cells in the airway that has been focused on is the airway epithelium. The airway epithelium is like the scene of the crime. The exposuresallergen, microbes, smoke, pollutantsare the first hit to the airway, so the airway epithelium has been the focus of potentially new drugs. Because of this, alarminsthese are the cytokines you mentioned, Reyincluding the thymic stromal lymphopoietin, which is TSLP, interleukin 33, and interleukin 25. These are the alarmins, which are important epithelial cytokines that drive inflammatory cascade down to the different pathways that we talked about: not only the T2 pathway but the non-T2 pathway. In fact, emerging data suggest that TSLP can play a key role in not only allergic inflammation but eosinophilic inflammation and, potentially, neutrophilic inflammation.

Which really makes you think, Why do we even need to phenotype? We give this blanket type of block, this type of cytokine. Tezepelumab is 1 of these more advanced monoclonal antibodies that blocks TSLP. There are several others: antiIL-33, inhaled TSLP. Tezepelumab is an injectable subcutaneous monoclonal antibody thats given for patients with severe asthma, in the hope that it blocks T2 inflammation. Were going to talk more about clinical trials. Some of these clinical trials show that it blocks non-T2 signals as well. Its certainly something that has been a long time in the making, and Im hoping well see the clinical outcomes, at least in our clinic. We know there are clinical studies that suggest that tezepelumab is good in its efficacy and safety.

Reynold Panettieri Jr, MD: Sid, any comments on Nics observations?

Sidney Braman, MD: Yeah. One other thing that we know about asthma is that if theres a virus around, and they catch that rhinovirus, or respiratory syncytial virus, or even severe influenza, theyre going to have an exacerbation. Its really well known that the virus stays around in the nose and throat longer. The viral shedding lasts much longer. We know that not only are the viral symptoms worse, but this causes more severe exacerbations. We also know that these viruses attack the epithelium. This is really 1 of the exciting aspects of the alarming storythe antialarming, like the anti-TSLP. Will they begin to show some effect on the other viral-induced respiratory exacerbation of asthma? Theres probably some reason to think so.

Reynold Panettieri Jr, MD: Yeah. The concept of the viral-mediated or toxic-mediated airway inflammation, which then extends exacerbations, is relatively straight insensitive too. We use steroids, of course, with an exacerbation. Dont get me wrong, but these are not the ones that are weakly resolved; not like a typical allergic exposure exacerbation. Those people really respond to steroids quickly. We see the viral, or the toxicant, patients languish a bit as we eventually get bored treating them with steroids and we taper them off. So you raised some really important points.

Thank you for watching this HCPLive Peer Exchange. If you enjoyed the content, please subscribe to our e-newsletters to receive upcoming Peer Exchanges and other great content right in your in-box. It comes to you wherever youre at: on your phone, in your office, or in your home. I want to thank everyone and our sponsors for this wonderful opportunity. Have a wonderful day, and be safe. Thank you.

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Tezepelumab as an Emerging Biologic to Treat Asthma - MD Magazine

Inotrem Receives Approval to Expand Nangibotide Clinical Trial in Critically Ill COVID-19 Patients and Receives Additional Public Funding of 45…

Posted: at 1:53 am

PARIS--(BUSINESS WIRE)--Inotrem S.A., a biotechnology company specializing in the development of immunotherapies targeting the TREM-1 pathway, announces that it has obtained authorization to pursue the clinical development of nangibotide up to registration in COVID-19 patients from both the French and Belgian competent authorities.

As part of this program, Inotrem receives additional 45 million euros in public funding under the "Capacity Building" Call for Expression of Interest, operated on behalf of the French government by Bpifrance, the French national investment bank, as part of the Programme dinvestissements davenir (PIA) and the France Recovery Plan, bringing French state support for the project to a total of 52,5 million euros. This public funding will support Inotrems clinical program including the phase 2/3 study ESSENTIAL which aims to demonstrate the efficacy and safety of nangibotide in treating patients in respiratory distress with severe forms of COVID-19.

The primary endpoint is evaluation of the impact of nangibotide on the progression of disease in patients receiving ventilatory support due to COVID-19 as well as on the severity of the respiratory failure, duration of mechanical ventilation, length of stay in intensive care and mortality. In ESSENTIAL, a Phase 2/3 clinical program, up to 730 patients will be enrolled initially in France and Belgium and, possibly in other European countries. Pre-defined interim analyses will be conducted by an independent Data Monitoring Board to test futility and to allow for the study design to be adapted as necessary. ESSNTIAL is the continuation of a 60 patients phase 2a evaluating the safety and efficacy of nangibotide in patients suffering from severe COVID-19. In July 2020, the CoviTREM-1 consortium, which includes the Nancy and Limoges university hospitals and Inotrem, obtained public funding of 7,5 million euros under the PSPC-COVID call for projects, operated on behalf of the French government by Bpifrance

New pre-clinical studies with nangibotide have demonstrated that the administration of nangibotide in murine models infected with SARS-CoV-2 was associated with a decrease in inflammatory mediators and an improvement of clinical signs, in particular respiratory function, and survival. Inotrem also confirmed in 3 different and independent cohorts that sTREM-1, a marker of the activation of the TREM-1 biological pathway, is associated with both severity and mortality in critically ill COVID-19 patients.

Leveraging the results of these preclinical studies and the implications for the role of the TREM-1 pathway in COVID-19, Inotrem has filed additional patents to cover nangibotide use in severe forms of COVID-19 as well as the use of sTREM-1 as a biomarker and companion diagnostic. This significantly strengthens Inotrems already broad patent estate.

Jean-Jacques Garaud, Executive Vice-President, Head of Scientific and Medical Affairs and Inotrems co-founder said :We are eager to pursue the development of nangibotide in these severe forms of COVID-19. Nangibotide is a TREM-1 inhibitor which has already demonstrated a trend towards efficacy in septic shock patients and has the potential to modulate the dysregulated immune response in critically ill COVID-19 patients. With this large clinical study, we can demonstrate efficacy for nangibotide in a further indication with the goals of reducing the duration of hospitalization and mortality.

Sven Zimmerman, CEO of Inotrem, also declared: The size of the financial support awarded to us as part of the French governments initiative against COVID-19 is a testimony to the relevance of targeting the TREM-1 pathway with nangibotide in these severely ill patients. We are delighted by the confidence placed in our technology and our team. Everyone at Inotrem is fully committed to deliver on this ambitious program alongside nangibotides ongoing Phase 2b trial in septic shock patients.

About InotremInotrem S.A. is a biotechnology company specialized in immunotherapy for acute and chronic inflammatory syndromes. The company has developed a new concept of immunomodulation that targets the TREM-1 pathway to control unbalanced inflammatory responses. Through its proprietary technology platform, Inotrem has developed the first-in-class TREM-1 inhibitor, LR12 (nangibotide), with potential applications in a number of therapeutic indications such as septic shock and myocardial infarction. In parallel, Inotrem has also launched another program to develop a new therapeutic modality targeting chronic inflammatory diseases. The company was founded in 2013 by Dr. Jean-Jacques Garaud, a former head of research and early development at the Roche Group, Prof. Sbastien Gibot and Dr. Marc Derive. Inotrem is supported by leading European and North American investors.


About TREM-1 pathwayTREM-1 pathway is an amplification loop of the immune response that triggers an exuberant and hyperactivated immune state which is known to play a crucial role in the pathophysiology of septic shock and acute myocardial infarction.

About NangibotideNangibotide is the formulation of the active ingredient LR12, which is a 12 amino-acid peptide prepared by chemical synthesis. LR12 is a specific TREM-1 inhibitor, acting as a decoy receptor and interfering in the binding of TREM-1 and its ligand. In preclinical septic shock models, nangibotide was able to restore appropriate inflammatory response, vascular function, and improved animals survival post septic shock.

About ESSENTIAL study:The Efficacy and Safety Study Exploring Nangibotide Treatment in COVID-19 pAtients with ventiLatory support, is a randomized, double-blind, placebo-controlled confirmatory study with adaptive features that will be performed in Europe. This is a pivotal study and it is expected that based on its results, nangibotide could be registered in this indication. The first part of the study (i.e.: 60 patients) has been already finalized and assessed by an independent data monitoring committee with excellent safety results. The study will recruit up to 730 patients in up to 40 sites. Several interim and futility analyses are foreseen as part of the adaptive design of the study.

About BpifranceBpifrance is the French national investment bank: it finances businesses at every stage of their development through loans, guarantees, equity investments and export insurances. Bpifrance also provides extra-financial services (training, consultancy.). to help entrepreneurs meet their challenges (innovation, export).For more information, please visit: http://www.bpifrance.fr and presse.bpifrance.frFollow us on Twitter: @Bpifrance - @BpifrancePresse

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Inotrem Receives Approval to Expand Nangibotide Clinical Trial in Critically Ill COVID-19 Patients and Receives Additional Public Funding of 45...

Wugen Raises $172 Million to Advance Clinical Stage Memory NK Cell Platform, Progress Best-In-Class AML Program, and Initiate Multiple Solid Tumor…

Posted: at 1:53 am

ST. LOUIS & SAN DIEGO--(BUSINESS WIRE)--Wugen, Inc., a clinical stage biotechnology company developing a pipeline of off-the-shelf cell therapies, today announced the completion of an oversubscribed $172 million Series B financing led by Abingworth and Tybourne Capital Management, and joined by new investors Fidelity Management & Research Company, Intermediate Capital Group (ICG), Sands Capital, Aisling Capital Management, Alexandria Venture Investments, Velosity Capital and Falcon Edge Capital. Existing investors, including RiverVest Venture Partners, LYZZ Capital, and Lightchain Capital, also participated. In connection with the financing, Bali Muralidhar, M.D., Ph.D., Managing Partner at Abingworth, Bosun Hau, Managing Director at Tybourne Capital Management, and Peter Kiener, Ph.D., Venture Partner at ICG, will join Wugens Board of Directors. The proceeds of the financing will support further clinical development of Wugens best-in-class memory natural killer (NK) cell platform and advance ongoing trials for patients with severe acute myelogenous leukemia (AML) and other oncology indications, including solid tumors. Wugen also plans to apply these proceeds to advance its broader pipeline of next-generation products into the clinic, including its allogeneic CD7-targeted CAR-T cell therapy to treat T-cell leukemia and lymphoma.

Dan Kemp, Ph.D., President and Chief Executive Officer of Wugen, said, We have tremendous confidence that our off-the-shelf memory NK cell platform will give rise to a significant pipeline of highly effective and safe anti-cancer therapies. In an ongoing Phase 1/2 clinical trial, our lead product WU-NK-101 has demonstrated an impressive complete response rate in relapsed/refractory AML and we look forward to advancing into a global multi-center study later this year. In parallel, were also pursuing solid tumor indications both as monotherapy and in combination with antibody drugs. The rapid growth of the company could not have happened without the commitment of RiverVest Venture Partners, and in particular the vision and leadership of John McKearn as our founding CEO.

Were delighted to welcome these premier investors as Wugen stakeholders as we build on the significant potential for the companys unique memory NK cell platform, said John McKearn, Ph.D., Managing Director at RiverVest Venture Partners and Chairman of the Board of Directors of Wugen. This significant capital raise will enable Wugen to advance its off-the-shelf cell therapies to develop a broad and differentiated oncology pipeline.

Wugens memory NK cell platform, with enhanced tumor-killing functionality and in vivo persistence, is designed to overcome the limitations of conventional NK cell therapies. In clinical studies, WU-NK-101 was shown to be highly effective against AML, including in patients with a high burden of disease, and without causing cytokine release syndrome (CRS) or neurotoxicity.

Wugen utilizes its proprietary GMP-grade fusion molecules to manufacture and scale its memory NK cell products using cells from healthy donors. In addition, Wugens feeder cell-free expansion and cryopreservation method enables an off-the-shelf treatment approach, with the opportunity for streamlined global distribution and convenient outpatient dosing for cancer patients.

Were excited to participate in this financing round with Wugen and are confident this exceptional team will deliver on the promise of memory NK cells, added Bali Muralidhar, M.D., Ph.D., Managing Director at Abingworth. We believe that Wugens strong collaborative partnership with Washington University is also a key strength, especially at the translational level, where co-founders and world-class investigators Todd Fehniger, M.D., Ph.D., John DiPersio, M.D., Ph.D., Melissa Berrien-Elliott, Ph.D., and Matt Cooper, Ph.D., who is also Wugens Chief Scientific Officer, provide critical support.

About Wugen

Wugen, Inc., is a clinical-stage biotechnology company developing a pipeline of off-the-shelf memory natural killer (NK) cell therapies to treat a broad range of hematological and solid tumor malignancies. Memory NK cells are hyper-functional, long-lasting immune cells that have evolved to attack cancer and respond to infection. Wugen is harnessing the power of this rare cell population by using its proprietary technologies to create WU-NK-101, currently in clinical development for acute myelogenous leukemia (AML). In addition, Wugen is developing a pipeline of programs targeting solid tumor indications. For more information, please visit http://www.wugen.com.

About Abingworth

Abingworth is a leading transatlantic life sciences investment firm. Abingworth helps transform cutting-edge science into novel medicines by providing capital and expertise to top calibre management teams building world-class companies. Since 1973, Abingworth has invested in over 170 life science companies, leading to 44 M&As and 71 IPOs. Abingworths therapeutic focused investments fall into three categories: seed and early-stage, development stage, and clinical co-development. Abingworth supports its portfolio companies with a team of experienced professionals at offices in London, Menlo Park (California), and Boston. For more information, please visit http://www.abingworth.com.

About Tybourne

Tybourne Capital Management is a global growth investor in public and private equity markets, focusing on investments in the Healthcare, Consumer, Financials and TMT sectors. The firm was founded in 2012 and is headquartered in Hong Kong with an office in San Francisco. Tybourne manages long duration capital on behalf of prominent non-profits, university endowments, sovereigns, corporate pensions and family offices. For more information, please visit http://www.tybournecapital.com.

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Wugen Raises $172 Million to Advance Clinical Stage Memory NK Cell Platform, Progress Best-In-Class AML Program, and Initiate Multiple Solid Tumor...

Dopavision Closes 12 Million Series A Round to Advance Digital Childhood Myopia Therapeutic Through Clinical Trials – Yahoo Finance

Posted: at 1:52 am

- Seventure Partners and Novartis Pharmaceuticals join as new investors- Transformative treatment for millions of children with myopia

Berlin, Germany, July 14, 2021 --- Dopavision, a company pioneering the development of digital therapeutics, today announced the closing of a 12 million Series A financing round. Seventure Partners led the round and was joined by Novartis Pharmaceuticals and the Companys existing shareholders such as Boehringer Ingelheim Venture Fund and Ababax Health, significantly broadening the Companys shareholder base of leading international life science investors.

Myopia is recognized as a public health concern and is the leading cause of correctable visual impairment, expected to reach a global prevalence of 50% by 2050. The condition manifests as blurring of distant objects due to image focusing in front of the retina instead of falling on the retina, most often caused by excessive elongation of the eyeball during growth. Severe cases are associated with sight-threatening conditions, including glaucoma, cataract, retinal detachment, and myopic maculopathy.

Halting disease progression in children and young adults at present is regarded as the most promising intervention approach to prevent severe impairments at a later age. Dopavisions mission is to support this myopia control strategy by providing transformative treatments and addressing the disease at an early stage, providing medical benefits for later years of life.

The proceeds will be used to fund the clinical development of MyopiaX, the Companys lead product in childhood myopia, with the goal to demonstrate its safety and efficacy in clinical studies and advance this innovative treatment to market to improve the lives of millions of myopic children. The breakthrough technology targets children and young adolescents, leveraging a patented, light-based technology that stimulates specific photosensitive cells of the retina, which in turn modulate retinal dopamine, a key neurotransmitter involved in eye growth. The Company has demonstrated proof-of-mechanism in preclinical models and exploratory human studies. MyopiaX has the potential to become the first digital therapy to control childhood myopia. It is designed to achieve a medical effect while children play exciting games or use educational digital content and can be conveniently integrated into their daily routine. It runs on standard digital devices and is easy to use for children under minimal supervision of their parents.

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Moreover, the funding will be dedicated to additional product development activities in order to provide innovative digital treatments for children leveraging games, educational or cognitive training applications, and potentially broaden the Companys pipeline to new indications. The Company also intends to continue to recruit and build a team of people passionate about using digital innovation to improve the lives of children and adults.

"We are excited that Seventure Partners and Novartis Pharmaceuticals have decided to support Dopavision as new investors in the Series A round," said Dr. Hamed Bahmani, co-founder and managing director of Dopavision. "The extensive use of smartphones is suspected to worsen childhood myopia but stopping children from using them is unrealistic. Therefore, we have decided to transform the use of digital devices into a beneficial therapeutic activity. Our first-of-its-kind MyopiaX combines ease of use with an exciting user experience that promotes adherence to the therapy with the goal of addressing this serious medical condition already at a young age."

"Novartis is committed to advancing transformational treatments - including digital therapeutics - to people of all ages living with visual impairment," said Jill Hopkins, Global Development Head, Ophthalmology, Novartis Pharmaceuticals.

"Dopavision is pursuing a unique digital therapeutic approach to achieve a significant clinical benefit," said Isabelle de Cremoux, CEO and Managing Partner of Seventure Partners. "This is the first real digital therapeutic for childhood myopia - a non-invasive, patient-friendly approach that will not only transform the global ophthalmology market, but also provide a breakthrough for affected children by improving their sight and quality of life from an early age onwards. Moreover, the technology has great potential for other disease indications as dopamine plays a key role in many physiological processes. Dopavision therefore excellently fits into our strategic commitment to develop groundbreaking digital health solutions."

To reflect the new shareholder structure, Dr. Annegret de Baey-Diepolder of Seventure Partners will join Dopavisions Advisory Board.


About Dopavision Dopavision is pioneering the development of digital therapeutics. As its lead product, the Company is developing a game-changing therapeutic for childhood myopia which can be seamlessly and invisibly integrated into the use of a smartphone. Myopia, or shortsightedness, is a visual condition that affects on average every third person globally, a share that has increased rapidly during the last two decades. It has grown to alarming proportions in Asia where prevalence rates, e.g. in Singapore, have reached 80% among young adults. High childhood myopia imposes a significant risk to cause visual impairment and even blindness later in life. Dopavisions goal is to develop a clinically validated therapy to halt myopia progression in children and adolescents. Founded in 2017 by Hamed Bahmani, Dopavision has so far raised 14.7 million in private equity and public grants and is backed by top-tier international investors such as Seventure Partners, Novartis Pharma and Boehringer Ingelheim Venture Fund. Dopavision is supported by the German government via the Industrie-in-Klinik program of the German Federal Ministry of Education and Research BMBF (Aktionsfeld Gesundheitswirtschaft im Rahmenprogramm Gesundheitsforschung, Forderkennzeichen/contract number 13GW0256). http://www.dopavision.com

About Seventure PartnersWith 850m net commitments under management as of the end of 2020, Seventure Partners is a leading venture capital firm in Europe. Since 1997, Seventure has been investing in innovative businesses with high growth potential in two fields: Life sciences across Europe, Israel, Asia and North America, and Digital technologies in France and Northern Europe.In life sciences, the main areas of focus include classic approaches such as biotechnology and pharmaceuticals, diagnostic and medtech, industrial biotechnology, as well as beyond the pill approaches such as microbiome-linked innovations, nutrition, foodtech, digital/connected health, wellbeing and personalized medicine & personalized nutrition. Investments can range between 500k and 10m per round, or up to 20m per company, from early to late stage, growth & pre-IPO. Seventure successfully launched Health for Life Capital which invests in life sciences (health, nutrition, digital/connected health) with a core focus on the microbiome revolution and its applications in human health, nutrition and food.In March 2018, Seventure launched AVF, a new fund dedicated to animal nutrition, feed and health with Adisseo as a strategic partner. In July 2019, it launched Sport & Performance Capital, dedicated to innovations in sport & wellness. The 160m first Health For Life Capital fund launched in 2014 has invested in 20 companies at the forefront of their fields, such as Enterome, Vedanta Biosciences, MaaT Pharma, Eligo Bioscience, Ysopia Bioscience, TargEDys, A-Mansia Biotech, BiomX, Microbiotica, LiMM Therapeutics, Siolta Therapeutics, DayTwo, Zipongo (renamed Foodsmart), Cambrooke, Mdoloris Medical Systems, MycoTechnology, etc. In January 2019 it launched the second fund Health for Life Capital II, now over 250m, which invested in Axial Therapeutics, BCD Biosciences, Citryll, Cytoki, Ervaccine, Federation Bio, Galecto etc. Both the first fund and second Health For Life Capital fund attracted strategic investments from prestigious organizations including Danone, Novartis, two US-based global food ingredient providers (to be disclosed), Lesaffre, Tornier, Tereos, Unigrains and Bel, as well as financial institutions, family offices and entrepreneurs. For more details: http://www.seventure.fr/en Twitter: @seventurep

About Boehringer Ingelheim Venture FundOperating as a separate legal entity, the Boehringer Ingelheim Venture Fund (BIVF) drives innovation through its strategic investments in early-stage science and technology. With an investment volume of 300 million Euro, the Venture Fund invests in biotech and start-up companies with innovative concepts and technologies that have the potential to provide ground-breaking platforms. BIVF currently holds a portfolio of more than 30 companies and creates companies when it identifies promising research projects in university and academia. BIVFs interest in young, mainly technology-oriented companies demonstrates its commitment to investigate new ideas and new science to create options for Boehringer Ingelheim to expand into new approaches and businesses in the field of Oncology, Regenerative Medicine, Infectious Diseases and Digital Health.


About Ababax HealthAbabax Health is a Digital Health technology company dedicated to developing Digital Drugs that enable tailored, non-invasive digital interventions to unlock and advance mental and physical health. Ababax pools Software-as-a-Drug competencies by uniting multidisciplinary scientists and technology experts to shape the future of medicine. The Ababax founders, Dr. Markus Mschenich and Christian Lautner, have been Founding Investors at Dopavision since 2017.


For further information please contact: Dopavision GmbH Stefan Zundel Managing Director info@dopavision.com

Media InquiriesakampionDr. Ludger Wess / Ines-Regina Buth Managing Partnersinfo@akampion.comTel. +49 40 88 16 59 64 /Tel. +49 30 23 63 27 68

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Dopavision Closes 12 Million Series A Round to Advance Digital Childhood Myopia Therapeutic Through Clinical Trials - Yahoo Finance

Oyster Point Pharma Announces Enrollment of First Subject in the OLYMPIA Phase 2 Clinical Trial of OC-01 (varenicline) Nasal Spray for Patients with…

Posted: June 22, 2021 at 1:52 am

PRINCETON, N.J., June 21, 2021 (GLOBE NEWSWIRE) -- Oyster Point Pharma, Inc. (Nasdaq: OYST), a clinical-stage biopharmaceutical company focused on the discovery, development and commercialization of first-in-class therapies to treat ophthalmic diseases, today announced enrollment of the first subject in the OLYMPIA Phase 2 clinical trial of OC-01 (varenicline) nasal spray for the treatment of Stage 1 Neurotrophic Keratopathy (NK).

This is an exciting milestone as we continue to develop this potentially new treatment option for patients with Stage 1 Neurotrophic Keratopathy, said Jeffrey Nau, Ph.D., MMS, president and chief executive officer of Oyster Point Pharma. We believe that NK affects more patients than are currently diagnosed as the disease has the potential to be undiagnosed or misdiagnosed. Stage 1 NK patients may present with additional ocular surface issues, including dry eye disease, which affects 38 million1 patients.

The OLYMPIA Phase 2 study is a multicenter, randomized, double-masked, placebo-controlled clinical trial to evaluate the safety and efficacy of OC-01 (varenicline) nasal spray in subjects with Mackies Classification Stage 1 Neurotrophic Keratopathy. The study is expected to enroll approximately 100 subjects at approximately 18 U.S. sites. In this clinical trial, OC-01 (varenicline) nasal spray will be administered three times a day, as compared to placebo (vehicle) nasal spray. The pre-specified primary endpoint of the trial will be the percentage of subjects who achieve complete resolution of fluorescein corneal staining at Day 56.

NK is characterized as a degenerative disease of the cornea due to impairment of trigeminal innervation that results in corneal epithelial damage, said Marian Macsai, M.D., chief medical officer of Oyster Point Pharma. We believe that OC-01 nasal spray may activate natural tear production through the trigeminal parasympathetic pathway, bypassing the impaired corneal nerves to stimulate the production of natural tear film and potentially improve corneal sensitivity and healing.

About Oyster Point PharmaOyster Point Pharma is a clinical-stage biopharmaceutical company focused on the discovery, development and commercialization of first-in-class therapies to treat ophthalmic diseases.

About OC-01 (varenicline) Nasal SprayOC-01 (varenicline) nasal spray is a highly selective cholinergic agonist being developed as a multidose preservative-free nasal spray to treat the signs and symptoms of dry eye disease and neurotrophic keratopathy. The parasympathetic nervous system, the rest and digest system of the body, controls tear film homeostasis partially via the trigeminal nerve, which is accessible within the nose. Administered as a preservative-free, aqueous nasal spray, in pre-clinical and clinical studies, OC-01 (varenicline) nasal spray was shown to have a novel mechanism of action with activation of the trigeminal parasympathetic pathway in the nasal cavity to activate natural tear film production. The human tear film is a complex mixture of more than 1,500 different proteins, including growth factors and antibodies, as well as numerous classes of lipids and mucins. This complex tear film is responsible for forming the primary refracting surface of the eye, as well as protecting and moisturizing the cornea. In December 2020, Oyster Point submitted to the U.S. Food and Drug Administration (FDA) a New Drug Application (NDA) for OC-01 (varenicline) nasal spray for the treatment of signs and symptoms of dry eye disease. The Prescription Drug User Fee Act (PDUFA) target action date is October 17, 2021, with a planned U.S. launch of OC-01 (varenicline) nasal spray in this indication in the fourth quarter of 2021, if approved by the FDA. OC-01 (varenicline) nasal spray is an investigational new drug and has not been approved for any use in any country. The safety and efficacy of OC-01 (varenicline) nasal spray have not been established.

About Neurotrophic KeratopathyNeurotrophic Keratopathy (NK) is a rare disease characterized by decreased corneal sensitivity and poor corneal healing. The most common causes of corneal sensation loss are viral infection (herpes simplex virus and herpes zoster keratoconjunctivitis), followed by chemical burns, physical injuries, and ocular surface surgery. In addition, systemic diseases such as diabetes and multiple sclerosis may decrease sensory nerve function or damage sensory fibers. NK can be classified broadly into three stages: Stage 1 (mild) consists of ocular surface irregularities and reduced vision, Stage 2 (moderate) exhibits a non-healing persistent defect of the corneal epithelium, and Stage 3 (severe) exhibits corneal ulceration, which may progress to corneal melting and perforation. If not adequately addressed, NK can lead to vision loss and a breakdown of corneal integrity, potentially leading to cornea transplantation.

Forward-Looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 that reflect the current beliefs, expectations and assumptions of the Company regarding the future of the Companys business, our future plans and strategies, regulatory approvals, clinical results, future financial condition and other future conditions. All statements other than statements of historical facts contained in this press release, including express or implied statements regarding product candidates, regulatory approvals, planned pre-clinical studies and clinical trials, expected results of pre-clinical studies or clinical trials, and their timing and likelihood of success, expected research and development costs, as well as plans and objectives of management for future operations, are forward-looking statements. The words if approved, may, will, should, would, expect, plan, anticipate, could, intend, target, project, contemplate, believe, estimate, predict, potential or continue or the negative of these terms or other similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. These forward-looking statements are subject to a number of risks, uncertainties and assumptions, including, among other things: the uncertainties inherent in pharmaceutical research and development, including pre-clinical study and clinical trial results and additional analysis of existing data, and the likelihood of our pre-clinical studies and clinical trials demonstrating the safety and efficacy of our product candidates, and other positive results; the timing of initiation of our future clinical trials, and the reporting of data from our current and future trials; the timing or likelihood of regulatory filings and approvals for our product candidates; our ability to obtain and maintain regulatory approvals of our product candidates; our plans relating to commercializing our product candidates, if approved; the success of competing therapies that are or may become available; the beneficial characteristics, safety, efficacy and therapeutic effects of our product candidates; our plans relating to the further pre-clinical and clinical development and manufacturing of our product candidates, including additional indications which we may pursue; the prevalence of dry eye disease and neurotrophic keratopathy and the size of the market opportunity for our product candidates; the expected potential benefits of strategic collaborations with third parties and our ability to attract collaborators with development, regulatory and commercialization expertise; our ability to recruit and retain key personnel needed to develop and commercialize our product candidates, if approved, and to grow our company; existing regulations and regulatory developments in the United States and other jurisdictions; our plans and ability to obtain or protect intellectual property rights, including extensions of existing patent terms where available; our continued reliance on third parties to conduct additional clinical trials of our product candidates, and for the manufacture of our product candidates for pre-clinical studies and clinical trials; the accuracy of our estimates regarding expenses, future revenue, capital requirements and needs for additional financing; our financial performance; market conditions; the sufficiency of our existing capital resources to fund our future operating expenses and capital expenditure requirements; and other risks described in the Risk Factors section included in our public filings that we have made and will make with the Securities and Exchange Commission. The Company is providing the information in this press release as of this date and does not undertake any obligation to update any forward-looking statements contained in this press release as a result of new information, future events or otherwise.

1- Market Scope 2020 Dry Eye Products Report: A Global Market Analysis for 2019 to 2025

Investor Contact:Tim McCarthyLifeSci Advisors, LLC(212) 915-2564investors@oysterpointrx.com

Media Contact:Sheryl Seapy, Real Chemistry(213) 262-9390sseapy@realchemistry.com

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Oyster Point Pharma Announces Enrollment of First Subject in the OLYMPIA Phase 2 Clinical Trial of OC-01 (varenicline) Nasal Spray for Patients with...

Spruce Biosciences Announces Publication of Phase 2 Results for Tildacerfont in Journal of Clinical Endocrinology and Metabolism – Business Wire

Posted: at 1:52 am

SAN FRANCISCO--(BUSINESS WIRE)--Spruce Biosciences, Inc. (Nasdaq: SPRB), a late-stage biopharmaceutical company focused on developing and commercializing novel therapies for rare endocrine disorders with significant unmet medical need, today announced the publication of the results from two Phase 2 clinical studies investigating tildacerfont in adult patients with classic CAH in the Journal of Clinical Endocrinology and Metabolism.

The data published in the Journal of Clinical Endocrinology and Metabolism demonstrates the potential of tildacerfont to reduce androgen excess without increasing the total daily glucocorticoid dose in patients with classic CAH, said Kyriakie Sarafoglou, MD, Associate Professor, Department of Pediatrics Divisions of Endocrinology and Genetics & Metabolism at the University of Minnesota Medical School.

SPR001-201 was an open-label, multi-dose, Phase 2a dose-escalation study which evaluated the ability of tildacerfont to lower adrenocorticotropic hormone (ACTH), 17-hydroxyprogesterone (17-OHP), and androstenedione (A4) at doses ranging from 200mg daily to 1,000mg daily in patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency. SPR001-202 was an open-label, 12-week Phase 2a clinical trial, which assessed the ability of a daily dose of 400mg of tildacerfont to lower ACTH, 17-OHP, and A4 over a 12-week dosing period. SPR001-201 and SPR001-202 comprised the entire Phase 2a clinical development program for tildacerfont in adult classic CAH. In the studies, efficacy was evaluated by changes from baseline in ACTH, 17-OHP, and A4 according to baseline A4 2x upper limit of normal (ULN), denoted as baseline good disease control, or A4 >2x ULN, denoted as baseline poor disease control. Safety was evaluated using adverse events and laboratory assessments.

The results of the studies showed that tildacerfont reduced key hormone biomarkers towards normal levels in the baseline poor disease control group, including normalization of ACTH and A4 in 60% and 40% of patients, respectively. In patients with baseline good disease control, these hormones were maintained near or below normal levels. Tildacerfont was generally safe and well-tolerated. The findings from these studies support the ongoing global late-stage studies of tildacerfont in adults with classic CAH CAHmelia-203 (assessing the ability of tildacerfont to reduce excessive adrenal androgens in patients with poor disease control) and CAHmelia-204 (assessing the ability of tildacerfont to reduce glucocorticoid usage in patients with good disease control while maintaining control of androgens).

Classic CAH is a serious and potentially life-threatening condition that has not benefited from new effective treatment options in approximately 50 years, said Rosh Dias, M.D., MRCP, Chief Medical Officer of Spruce Biosciences. People living with classic CAH must grapple with the difficult balance of managing their adrenal androgen excess and supraphysiologic dosing of glucocorticoids, the existing standard of care therapy. In our Phase 2a studies, I was pleased to see that tildacerfont was able to produce meaningful reductions in highly elevated hormones in classic CAH patients, including in some cases normalization of these hormones, over a 12-week period without increases to daily steroid doses. This has not been reported to date with any other investigational product candidate.

About Tildacerfont

Tildacerfont is a potent and highly selective, non-steroidal, oral antagonist of the CRF1 receptor, which is the receptor for corticotropin-releasing factor (CRF), a hormone that is secreted by the hypothalamus. The CRF1 receptor is abundantly expressed in the pituitary gland where it is the primary regulator of the HPA axis. By blocking the CRF1 receptor, tildacerfont has the potential to address the uncontrolled cortisol feedback regulatory pathway in CAH, and in turn reduce the production of ACTH in the pituitary, limiting the amount of androgen produced downstream from the adrenal gland. Tildacerfont has been evaluated in 171 patients across seven clinical trials in which it has been generally well tolerated. No drug-related serious adverse events have been reported related to tildacerfont treatment.

About Spruce Biosciences

Spruce Biosciences is a late-stage biopharmaceutical company focused on developing and commercializing novel therapies for rare endocrine disorders with significant unmet need. Spruce is initially developing its wholly owned product candidate, tildacerfont, as the potential first non-steroidal therapy for patients suffering from classic congenital adrenal hyperplasia (CAH). Classic CAH is a serious and life-threatening disease with no known novel therapies approved in approximately 50 years. Spruce is also developing tildacerfont for women suffering from a rare form of polycystic ovary syndrome (PCOS) with primary adrenal androgen excess. To learn more, visit http://www.sprucebiosciences.com and follow us on Twitter @Spruce_Bio, LinkedIn, Facebook and YouTube.

Forward-Looking Statements

Statements contained in this press release regarding matters that are not historical facts are forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Such forward-looking statements include statements regarding, among other things, the results, conduct, progress and timing of Spruces clinical trials. Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. Words such as potential, demonstrates, may and similar expressions are intended to identify forward-looking statements. These forward-looking statements are based upon Spruces current expectations and involve assumptions that may never materialize or may prove to be incorrect. Actual results could differ materially from those anticipated in such forward-looking statements as a result of various risks and uncertainties, which include, without limitation, risks and uncertainties associated with Spruces business in general, the impact of the COVID-19 pandemic, and the other risks described in Spruces filings with the U.S. Securities and Exchange Commission. All forward-looking statements contained in this press release speak only as of the date on which they were made and are based on managements assumptions and estimates as of such date. Spruce undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made, except as required by law.

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Spruce Biosciences Announces Publication of Phase 2 Results for Tildacerfont in Journal of Clinical Endocrinology and Metabolism - Business Wire

GSK and Vir Biotechnology Announce Continuing Progress of the COMET Clinical Development Program for Sotrovimab – BioSpace

Posted: at 1:52 am

LONDON and SAN FRANCISCO, June 21, 2021 (GLOBE NEWSWIRE) -- GlaxoSmithKline plc (LSE/NYSE: GSK) and Vir Biotechnology, Inc. (Nasdaq: VIR) today announced final, confirmatory results from the Phase 3 COMET-ICE (COVID-19 Monoclonal antibody Efficacy Trial Intent to Care Early) trial demonstrating that sotrovimab, an investigational SARS-CoV-2 monoclonal antibody, significantly reduced the risk of hospitalization or death among high-risk adult outpatients with mild-to-moderate COVID-19. Additionally, the U.S. National Institutes of Health (NIH) updated its COVID-19 treatment guidelines to recommend sotrovimab for non-hospitalized patients with mild-to-moderate COVID-19 who are at high risk of clinical progression and noted that sotrovimab appears to retain activity against current variants of concern and interest.

The primary efficacy analysis of all 1,057 patients in the COMET-ICE trial demonstrated a 79% reduction (adjusted relative risk reduction) (p<0.001) in hospitalization for more than 24 hours or death due to any cause, by Day 29 compared to placebo, meeting the primary endpoint of the trial.

The number of patients in the trial who were hospitalized for >24 hours for acute management of any illness or death from any cause at Day 29 was six patients in the sotrovimab arm (1%), versus 30 patients in the placebo arm (6%). In the sotrovimab arm, it is possible that half of those patients who were hospitalized were for reasons other than progression of COVID-19 (e.g., small bowel obstruction, lung cancer and diabetic foot ulcer); this was not the case for patients in the placebo arm. In the safety analysis, 1,037 participants were followed through at least 29 days. The most common adverse events observed in the sotrovimab treatment group in COMET-ICE were rash (1%) and diarrhea (2%), all of which were Grade 1 (mild) or Grade 2 (moderate). No other treatment-emergent adverse events were reported at a higher rate with sotrovimab compared to placebo. The companies plan to submit the full COMET-ICE data set to a peer-reviewed journal for publication.

Christopher Corsico, senior vice president of development, GSK, said: Effective medicines to treat those who become infected with SARS-CoV-2 remain a critical part of the solution to this pandemic. We are working diligently to increase access to sotrovimab in the U.S. and across the globe, including evaluating the potential to simplify administration with an intramuscular formulation.

George Scangos, Ph.D., chief executive officer of Vir, said: We are pleased that the profound interim efficacy from the COMET-ICE trial has now been validated by the full study population. These results, combined with the growing number of pending global authorizations, as well as the recent recommendation by the NIH COVID-19 Treatment Guidelines Panel, support our confidence in the potential role of sotrovimab in the fight against this pandemic.

Updated NIH Guidelines Recommend SotrovimabThe NIH recently updated its guidelines regarding the emergency use authorizations of anti-SARS-CoV-2 monoclonal antibodies for the treatment of COVID-19 in the U.S. to recommend the use of sotrovimab for non-hospitalized patients with mild-to-moderate COVID-19 who are at high risk of clinical progression. The guidelines note that the target binding site of sotrovimab is in a region of the virus that does not overlap with the binding site location of key mutations in current variants of concern and interest. These guidelines were based upon an interim analysis of 583 patients in the COMET-ICE trial, which was stopped early in March 2020 by an independent data monitoring committee because interim results demonstrated evidence of sotrovimabs clinical efficacy. The interim study results demonstrated an 85% (p=0.002) reduction in hospitalization for more than 24 hours or death in those receiving sotrovimab compared to placebo, the primary endpoint of the trial.

These data have informed global regulatory reviews to date, including the positive scientific opinion issued by the European Medicines Agencys (EMA) Committee for Human Medicinal Products (CHMP) under Article 5(3) of Regulation 726/2004, as well as the Emergency Use Authorization (EUA) granted by the U.S. Food and Drug Administration (FDA).

The companies are actively working with government agencies around the world to make sotrovimab available to patients in need of treatment.

Continued Progress with the COMET Clinical Development ProgramThe companies are also pleased to announce continued progress with the robust COMET clinical development program, which aims to provide clinical evidence from several studies over the course of the next year.

GSK and Vir are committed to ongoing evaluation of sotrovimab as the COVID-19 landscape continues to evolve at different rates across the globe and new variants of concern and interest emerge. Data from in vitro studies, published in bioRxiv, have demonstrated that sotrovimab maintains activity against circulating variants of concern and interest, including the Gamma (P.1), Epsilon (B.1.427/B.1.429), Delta (B.1.617.1), Iota (B.1.526), Beta (B.1.351) and Alpha (B.1.1.7) variants. GSK and Vir are continuing to evaluate the ability of sotrovimab to maintain activity against new and emerging variants through in vitro studies. The clinical impact of this in vitro variants data is not yet known.

About Sotrovimab (previously VIR-7831)Sotrovimab is an investigational SARS-CoV-2 monoclonal antibody. Preclinical data suggest it has the potential to both block viral entry into healthy cells and clear infected cells. The antibody binds to an epitope on SARS-CoV-2 that is shared with SARS-CoV-1 (the virus that causes SARS), indicating that the epitope is highly conserved, which may make it more difficult for resistance to develop. Sotrovimab, which incorporates Xencors Xtend technology, also has been designed to achieve high concentration in the lungs to ensure optimal penetration into airway tissues affected by SARS-CoV-2 and to have an extended half-life.

The following is a summary of information for sotrovimab. Healthcare providers in the U.S. should review the Fact Sheets for information on the authorized use of sotrovimab and mandatory requirements of the EUA. Please see the FDA Letter of Authorization, Fact Sheet for Healthcare Providers, and Fact Sheet for Patients, Parents, and Caregivers. For more information on the EMA positive scientific opinion, please review the EU Conditions of Use.

Important Information about SotrovimabSotrovimab has been authorized by the FDA for the emergency use described below. Sotrovimab is not FDA-approved for this use.

Sotrovimab is authorized only for the duration of the declaration that circumstances exist justifying the authorization of the emergency use of sotrovimab under section 564(b)(1) of the Act, 21 U.S.C. 360bbb-3(b)(1), unless the authorization is terminated or revoked sooner.

Authorized Use The U.S. Food and Drug Administration (FDA) has issued an Emergency Use Authorization (EUA) to permit the emergency use of the unapproved product sotrovimab for the treatment of mild-to-moderate coronavirus disease 2019 (COVID-19) in adults and pediatric patients (12 years of age and older weighing at least 40 kg) with positive results of direct SARS-CoV-2 viral testing, and who are at high risk for progression to severe COVID-19, including hospitalization or death.

Limitations of Authorized Use Sotrovimab is not authorized for use in patients:

Benefit of treatment with sotrovimab has not been observed in patients hospitalized due to COVID-19. SARS-CoV-2 monoclonal antibodies may be associated with worse clinical outcomes when administered to hospitalized patients with COVID-19 requiring high flow oxygen or mechanical ventilation.

Important Safety Information for Sotrovimab


There are limited clinical data available for sotrovimab. Serious and unexpected adverse events may occur that have not been previously reported with sotrovimab use.

Hypersensitivity Including Anaphylaxis and Infusion-Related Reactions

Serious hypersensitivity reactions, including anaphylaxis have been observed with administration of sotrovimab. If signs and symptoms of a clinically significant hypersensitivity reaction or anaphylaxis occur, immediately discontinue administration and initiate appropriate medications and/or supportive care.

Infusion-related reactions, occurring during the infusion and up to 24 hours after the infusion, have been observed with administration of sotrovimab. These reactions may be severe or life threatening.

Signs and symptoms of infusion-related reactions may include: fever, difficulty breathing, reduced oxygen saturation, chills, fatigue, arrhythmia (eg, atrial fibrillation, sinus tachycardia, bradycardia), chest pain or discomfort, weakness, altered mental status, nausea, headache, bronchospasm, hypotension, hypertension, angioedema, throat irritation, rash including urticaria, pruritus, myalgia, vaso-vagal reactions (eg, pre-syncope, syncope), dizziness and diaphoresis.

Consider slowing or stopping the infusion and administer appropriate medications and/or supportive care if an infusion-related reaction occurs.

Hypersensitivity reactions occurring more than 24 hours after the infusion have also been reported with the use of SARS-CoV-2 monoclonal antibodies under Emergency Use Authorization.

Clinical Worsening After SARS-CoV-2 Monoclonal Antibody Administration

Clinical worsening of COVID-19 after administration of SARS-CoV-2 monoclonal antibody treatment has been reported and may include signs or symptoms of fever, hypoxia or increased respiratory difficulty, arrhythmia (eg, atrial fibrillation, tachycardia, bradycardia), fatigue, and altered mental status. Some of these events required hospitalization. It is not known if these events were related to SARS-CoV-2 monoclonal antibody use or were due to progression of COVID-19.

Limitations of Benefit and Potential for Risk in Patients with Severe COVID-19

Benefit of treatment with sotrovimab has not been observed in patients hospitalized due to COVID-19. SARS-CoV-2 monoclonal antibodies may be associated with worse clinical outcomes when administered to hospitalized patients with COVID-19 requiring high flow oxygen or mechanical ventilation. Therefore, sotrovimab is not authorized for use in patients: who are hospitalized due to COVID-19, OR who require oxygen therapy due to COVID-19, OR who require an increase in baseline oxygen flow rate due to COVID-19 in those on chronic oxygen therapy due to underlying non-COVID-19 related comorbidity.


The most common treatment-emergent adverse events observed in the sotrovimab treatment group in COMET-ICE were rash (2%) and diarrhea (1%), all of which were Grade 1 (mild) or Grade 2 (moderate). No other treatment-emergent adverse events were reported at a higher rate with sotrovimab compared to placebo.



There are insufficient data to evaluate a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcome. Sotrovimab should be used during pregnancy only if the potential benefit justifies the potential risk for the mother and the fetus.


There are no available data on the presence of sotrovimab in human milk, the effects on the breastfed infant, or the effects on milk production. Individuals with COVID-19 who are breastfeeding should follow practices according to clinical guidelines to avoid exposing the infant to COVID-19.

About the Vir and GSK CollaborationIn April 2020, Vir and GSK entered into a collaboration to research and develop solutions for coronaviruses, including SARS-CoV-2, the virus that causes COVID-19. The collaboration uses Virs proprietary monoclonal antibody platform technology to accelerate existing and identify new anti-viral antibodies that could be used as therapeutic or preventive options to help address the current COVID-19 pandemic and future outbreaks. The companies will leverage GSKs expertise in functional genomics and combine their capabilities in CRISPR screening and artificial intelligence to identify anti-coronavirus compounds that target cellular host genes. They will also apply their combined expertise to research SARS-CoV-2 and other coronavirus vaccines.

GSK Commitment to Tackling COVID-19GSKs response to COVID-19 has been one of the broadest in the industry, with three potential treatments in addition to our vaccine candidates in development with partner organizations.

GSK is collaborating with several organizations on COVID-19 vaccines by providing access to our adjuvant technology. In addition to our work with Medicago, we recently announced positive Phase 2 data from our collaboration with Sanofi to develop an adjuvanted, protein-based vaccine candidate and expect to begin a Phase 3 trial in Q2. An earlier stage collaboration with SK Bioscience is also ongoing. SK Bioscience receives funding from CEPI and the Bill and Melinda Gates Foundation to develop differentiated, affordable COVID-19 vaccines for supply globally through the COVAX facility. The use of an adjuvant can be of particular importance in a pandemic since it may reduce the amount of vaccine protein required per dose, allowing more vaccine doses to be produced and contributing to protecting more people.

GSK is also working with mRNA specialist, CureVac, to jointly develop next generation, multi-valent mRNA vaccines for COVID-19 with the potential to address multiple emerging variants in one vaccine. GSK will also support manufacturing of up to 100m doses of CureVacs first generation COVID-19 vaccine. GSK is also providing manufacturing support for up to 60m doses of Novavax COVID-19 vaccine in the UK.

GSK is also exploring potential therapeutic or treatment options for COVID-19 patients. We are collaborating with Vir Biotechnology to develop existing and identify new anti-viral antibodies that could be used as therapeutic or preventive options for COVID-19. We reported that an Independent Data Monitoring Committee recommended that the Phase 3 COMET-ICE trial evaluating sotrovimab as monotherapy for the early treatment of COVID-19 in adults at high risk of hospitalization be stopped for enrollment due to evidence of profound efficacy, based on an interim analysis of data from the trial. An analysis of data through Day 29 of the COMET-ICE trial was consistent with interim results. We have received Emergency Use Authorization in the U.S. and are seeking authorizations in other countries. We are also assessing whether an investigational monoclonal antibody, otilimab, can help severely ill COVID-19 patients aged over 70 who experience an overreaction of their immune system.

Virs Commitment to COVID-19Vir was founded with the mission of addressing the worlds most serious infectious diseases. In 2020, Vir responded rapidly to the COVID-19 pandemic by leveraging our unique scientific insights and industry-leading antibody platform to explore multiple monoclonal antibodies as potential therapeutic or preventive options for COVID-19. Sotrovimab is the first SARS-CoV-2-targeting antibody Vir advanced into the clinic. It was carefully selected for its demonstrated promise in preclinical research, including an anticipated high barrier to resistance and potential ability to both block the virus from entering healthy cells and clear infected cells. Vir is continuing to pursue novel therapeutic and prophylactic solutions to combat SARS-CoV-2 and future coronavirus pandemics, both independently and in collaboration with its partners.

About GSK GSK is a science-led global healthcare company with a special purpose: to help people do more, feel better, live longer. For further information please visit http://www.gsk.com/about-us.

About Vir Biotechnology

Vir Biotechnology is a clinical-stage immunology company focused on combining immunologic insights with cutting-edge technologies to treat and prevent serious infectious diseases. Vir has assembled four technology platforms that are designed to stimulate and enhance the immune system by exploiting critical observations of natural immune processes. Its current development pipeline consists of product candidates targeting COVID-19, hepatitis B virus, influenza A and human immunodeficiency virus. For more information, please visit http://www.vir.bio.

GSK Cautionary Statement Regarding Forward-Looking StatementsGSK cautions investors that any forward-looking statements or projections made by GSK, including those made in this announcement, are subject to risks and uncertainties that may cause actual results to differ materially from those projected. Such factors include, but are not limited to, those described in the Company's Annual Report on Form 20-F for 2020 and any impacts of the COVID-19 pandemic.

Vir Forward-Looking StatementsThis press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Words such as may, will, plan, potential, aim, promising and similar expressions (as well as other words or expressions referencing future events, conditions or circumstances) are intended to identify forward-looking statements. These forward-looking statements are based on Virs expectations and assumptions as of the date of this press release. Forward-looking statements contained in this press release include, but are not limited to, statements regarding the final data from the COMET-ICE trial, NIH guidelines recommending the use of sotrovimab in the treatment of COVID-19, the initiation of Virs COMET-TAIL clinical trial, the clinical development program for sotrovimab, Virs capacity to manufacture and supply sotrovimab, the ability of sotrovimab to treat and/or prevent COVID-19, the ability of sotrovimab to maintain activity against circulating variants of concern, and statements related to regulatory authorizations and approvals, including plans and discussions with the FDA, EMA and other global regulators. Many factors may cause differences between current expectations and actual results, including unexpected safety or efficacy data observed during preclinical or clinical studies, challenges in the treatment of hospitalized patients, difficulties in collaborating with other companies or government agencies, challenges in accessing manufacturing capacity, successful development and/or commercialization of alternative product candidates by Virs competitors, changes in expected or existing competition, delays in or disruptions to Virs business or clinical trials due to the COVID-19 pandemic, geopolitical changes or other external factors, and unexpected litigation or other disputes. Other factors that may cause actual results to differ from those expressed or implied in the forward-looking statements in this press release are discussed in Virs filings with the U.S. Securities and Exchange Commission, including the section titled Risk Factors contained therein. Except as required by law, Vir assumes no obligation to update any forward-looking statements contained herein to reflect any change in expectations, even as new information becomes available.

Registered in England & Wales:No. 3888792

Registered Office:980 Great West RoadBrentford, MiddlesexTW8 9GS

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GSK and Vir Biotechnology Announce Continuing Progress of the COMET Clinical Development Program for Sotrovimab - BioSpace

CytomX Therapeutics Announces Publication of First-in-Human Data for CX-2029 in Clinical Cancer Research – GlobeNewswire

Posted: at 1:52 am

SOUTH SAN FRANCISCO, Calif., June 21, 2021 (GLOBE NEWSWIRE) -- CytomX Therapeutics, Inc. (Nasdaq: CTMX), a clinical-stage oncology-focused biopharmaceutical company pioneering a novel class of investigational conditionally activated therapeutics based on its Probody technology platform, today announced that results from its Phase 1 first-in-human study of CX-2029 in patients with advanced solid tumors were published online in the peer-reviewed journal Clinical Cancer Research. This study showed that CX-2029, currently being co-developed by CytomX and AbbVie, was generally well-tolerated and can elicit anti-tumor responses in certain patients.

These results highlight that our industry-leading Probody platform can be successfully leveraged to create conditionally activated ADCs against previously undruggable targets. For the first time, CD71 has been shown to be a viable therapeutic cancer target, said Alison L. Hannah, M.D., senior vice president and chief medical officer of CytomX Therapeutics.

CD71 is a cell surface protein essential for iron uptake in dividing cells and is highly expressed in a number of solid and hematologic cancers. However, given its central role in iron metabolism, CD71 is present on most healthy cells and has been, until now, undruggable with conventional ADCs. CX-2029 is designed to be activated in the tumor microenvironment by tumor-associated proteases, thereby limiting off-tumor toxicity and creating a therapeutic window for CD71.

The goal of this Phase 1 dose-escalation, multicenter study was to evaluate the safety, pharmacokinetics, pharmacodynamics, and antitumor activity of CX-2029. A total of 45 patients were enrolled to receive CX-2029 intravenously every three weeks at dose levels ranging from 0.1 mg/kg to 5 mg/kg.

Encouraging preliminary clinical activity was observed at doses of 2 mg/kg and higher. Notably, three of four patients with squamous non-small cell lung carcinoma (NSCLC) had stable disease (SD) or better, including two confirmed partial responses (PRs) (at doses of 3 and 5 mg/kg); and seven of eight patients with head and neck squamous cell carcinoma (HNSCC) had SD or better, including one confirmed PR at 3 mg/kg and one prolonged SD ongoing at approximately 25 weeks, as of the reported August 2020 data cutoff.

Despite having received a median of three prior lines of cancer regimens (range, 116), these heavily-pretreated patients generally tolerated CX-2029 well. The most common dose-dependent adverse events were anemia and neutropenia, toxicities commonly associated with the payload of this ADC (monomethyl auristatin E). Based on several safety parameters, including no cycle 1 DLTs, no discontinuations due to toxicity, and a long-term tolerability that appeared to be acceptable for chronic administration with supportive care for anemia, 3 mg/kg every 3 weeks was declared the recommended Phase 2 dose.

The ongoing Phase 2 expansion study is evaluating CX-2029 as monotherapy in four cohorts: squamous NSCLC, HNSCC, esophageal and gastroesophageal junction cancers (both adenocarcinoma and squamous histologies), and diffuse large B-cell lymphoma. Initial results are expected in the fourth quarter of 2021.

AboutCytomX TherapeuticsCytomX is a clinical-stage, oncology-focused biopharmaceutical company with a vision of transforming lives with safer, more effective therapies. We are developing a novel class of investigational conditionally activated therapeutics, based on our Probody technology platform, for the treatment of cancer. CytomX has strategic drug discovery and development collaborations with AbbVie, Amgen, Astellas, and Bristol Myers Squibb.

Probody therapeutics are conditionally activated biologics designed to remain inactive until they are activated by proteases in the tumor microenvironment. As a result, Probody therapeutics are intended to bind selectively to tumors and decrease binding to healthy tissue, to minimize toxicity and potentially create safer, more effective therapies. As leaders in the field, our innovative technology is designed to turn previously undruggable targets into druggable targets and to enable more effective combination therapies. CytomX and its partners, comprised of leading biotechnology and pharmaceutical companies, have developed a robust pipeline of potential first-in-class therapeutic candidates against novel, difficult to drug targets and potential best-in-class immunotherapeutic candidates against clinically validated targets. The CytomX clinical-stage pipeline comprises five assets, four of which are in Phase 2 clinical studies. First-in-class product candidates against previously undruggable targets include a CD166-targeting conditionally activated antibody-drug conjugate wholly owned by CytomX (praluzatamab ravtansine, CX-2009) and a CD71-targeting conditionally activated antibody-drug conjugate partnered with AbbVie (CX-2029). CD166 and CD71 are among cancer targets that are considered to be inaccessible to conventional antibody-drug conjugates due to their presence on many healthy tissues. The CytomX clinical-stage pipeline also includes cancer immunotherapeutic candidates against validated targets such as the CTLA-4-targeting Probodies, BMS-986249 and BMS-986288, partnered with Bristol Myers Squibb, and our wholly-owned conditionally activated anti-PD-L1 antibody, pacmilimab (CX-072). For additional information about CytomX Therapeutics, visit http://www.cytomx.com and follow us on LinkedIn and Twitter.

CytomX Therapeutics Forward-Looking StatementsThis press release includes forward-looking statements. Such forward-looking statements involve known and unknown risks, uncertainties and other important factors that are difficult to predict, may be beyond our control, and may cause the actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied in such statements. Accordingly, you should not rely on any of these forward-looking statements, including those relating to the potential benefits, safety and efficacy or progress of CytomXs or any of its collaborative partners product candidates, including praluzatamab ravtansine (CX-2009), CX-2029, BMS-986249, BMS-986288, and pacmilimab (CX-072), the potential benefits or applications of CytomXs Probody platform technology, CytomXs ability to develop and advance product candidates into and successfully complete clinical trials, including the ongoing and planned clinical trials of praluzatamab ravtansine, CX-2029, BMS-986249, BMS-986288, and pacmilimab (CX-072), and the timing of the commencement of clinical trials and other development milestones. Risks and uncertainties that contribute to the uncertain nature of the forward-looking statements include: the unproven nature of CytomXs novel Probody platform technology; CytomXs clinical trial product candidates are in the initial stages of clinical development and its other product candidates are currently in preclinical development, and the process by which preclinical and clinical development could potentially lead to an approved product is long and subject to significant risks and uncertainties, including the risk that the COVID-19 worldwide pandemic may continue to negatively impact the business, research and clinical operations of CytomX or its partners, including the development of preclinical drug candidates due to delays in and disruption of research activities and the development of clinical drug candidates due to delays in or disruption of clinical trials, including impacts on the enrollment of patients in clinical trials or other clinical trial disruptions; the possibility that the results of early clinical trials may not be predictive of future results, including clinical trials for CX-2029; the possibility that CytomXs clinical trials will not be successful; the possibility that current preclinical research may not result in additional product candidates; CytomXs dependence on the success of praluzatamab ravtansine, CX-2029, BMS-986249, BMS-986288, and pacmilimab (CX-072); CytomXs reliance on third parties for the manufacture of the companys product candidates; and possible regulatory developments inthe United Statesand foreign countries. Additional applicable risks and uncertainties include those relating to our preclinical research and development, clinical development, and other risks identified under the heading "Risk Factors" included in CytomXs Quarterly Report on Form 10-Q filed with theSEConMay 6, 2021. The forward-looking statements contained in this press release are based on information currently available to CytomX and speak only as of the date on which they are made. CytomX does not undertake and specifically disclaims any obligation to update any forward-looking statements, whether as a result of any new information, future events, changed circumstances or otherwise.

Probody is a U.S. registered trademark of CytomX Therapeutics, Inc.

CytomX Contact:Chau Cheng, PhD MBAVP, Investor Relations & Corp. Communicationsccheng@cytomx.comDirect: (650) 273-4999

Investor and Media Contact:Stern Investor RelationsStephanie Ascherstephanie.ascher@sternir.com212-362-1200

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CytomX Therapeutics Announces Publication of First-in-Human Data for CX-2029 in Clinical Cancer Research - GlobeNewswire

COVID-19: India Has a Habit of Bad Clinical Trials – The Wire Science

Posted: at 1:52 am

Representative: A health official draws a dose of Covishield in Colombo, Sri Lanka, January 29, 2021. Photo: Reuters/Dinuka Liyanawatte/File Photo

Mumbai: On June 15, All India Institute of Medical Sciences (AIIMS), Delhi, started inoculating children with Covaxin as part of Bharat Biotechs paediatric clinical trial to evaluate the safety, reactogenicity and immunogenicity of Covaxin in 2- to 18-year-old children.

The trial plans to enrol around 525 children across hospitals. This is a very small cohort. For example, Modernas paediatric trial aims to recruit 7,050 children aged 6 months to 12 years. It had conducted another trial with 3,732 teenagers aged 12-18 years. Similarly, Pfizer is conducting a paediatric trial with 4,644 children aged 6 months to 12 years; and its trial with adolescents enrolled 2,260 participants aged 12-15 years.

Experts have raised concerns about Bharat Biotechs trial over its small size, and because it doesnt have a placebo arm.

And while the criticism is significant, it may not be limited to Bharat Biotech.

The Hyderabad-based pharmaceutical companys small paediatric trial is one of many clinical studies conducted in India that have, or intend to have, a small number of participants.

Such studies are said to be underpowered. According to one 2007 paper, a studys power is the probability of saying there is a difference when a difference actually exists. An underpowered study does not have a sufficiently large sample size to answer the research question of interest.

It is possible to calculate the ideal sample size before the trial begins. This means while trial investigators can write off an inconclusive result as the product of the small sample size, theyre expected to have good reasons for why they didnt include more participants.

However, Indias drug regulator, the Drug Controller General, has complicated this picture, especially in the last couple years. It has passively condoned underpowering by awarding the fruits of such trials with emergency use approvals. Itolizumab was okayed after a trial with 30 participants, favipiravir with 150 participants, Virafin with 290 participants (40 and 250 in phase 2 and 3 trials) and 2-deoxy-d-glucose with 330 participants (110 and 220 in phase 2 and 3 trials).

Also read: Is Biocons Itolizumab Good News? Hard to Tell, Thanks to the Bad Science.

* * *

Randomised control trials are difficult to conduct more so with a crumbling health infrastructure in the middle of an epidemic but this isnt an acceptable excuse to not have one.

Conducting multiple small trials with a few hundred participants is not the same as conducting one large trial with thousands. When the former are summed up, their underpoweredness is magnified, rendering the total findings less than useful.

In India, researchers who plan to conduct clinical studies involving human participants need to register each study on the Clinical Trial Registry of India (CTRI) before it begins. Since the pandemic began, more than 1,300 such trials have been registered on CTRI.

Not all trials are completed; many never kick off and many others stop midway, for multiple reasons. This said, Indias COVID-19 research output has still been piddling especially in quality, because most studies are underpowered and often methodologically flawed as well.

For example, there are at least 15 trials registered on CTRI involving hydroxychloroquine, the drug that India pushed in a big way in 2020. These trials together include thousands of patients but they produced little usable evidence last year.

Instead, all the evidence we have on the efficacy of different drugs has come from large adaptive trials, especially the WHOs SOLIDARITY, the UKs RECOVERY and the USs ACTT trials.

(Researchers sometimes unearth important patterns by studying multiple small trials together. However, this isnt possible when the trials measure different parameters, thus arriving at incomparable outcomes.

For example, trials for hydroxychloroquine at AIIMS Delhi, with 116 participants, and at AIIMS Raipur, with 50 measured progression to severe disease and virological clearance at day six, with no overlap.)

No country for negative trials

Another problem is publication bias when researchers dont publish their results because the latter are deemed to be insignificant.

For example, Mumbai-based Wockhardt conducted a trial for convalescent plasma in May 2020. In a meeting with experts at the Central Drug Standards Control Organisation on February 11, 2021, Wockhardt submitted that its trial failed to show any benefit with plasma but it hasnt published a paper detailing the trials results. The PLATINA trial in Maharashtra met a similar fate.

Emails to researchers involved in both trials hadnt elicited a response at the time of publishing this article.

Not publishing the results of a trial is a breach of the ethical obligations that researchers have towards study participants, and is a grave injustice to our people, Dr Aju Mathew, an epidemiologist and a cancer specialist in Kochi, told The Wire Science.

In a study published in December 2020, Dr Mathew and his peers found that only 55% of cancer trials registered in India were eventually published. They also reported that trials conducted by international pharmaceutical companies were more likely to be published than Indian ones.

Publication bias can have a serious impact on patient care. COVID-19 is a new disease: before drug trials got underway, healthcare workers drew on their experience and education to make informed guesses about treatments to administer. Negative results in this regard can help workers improve their protocols by subtracting bad options.

Indeed, institutions around the world dropped drugs like hydroxychloroquine, lopinavir and ritonavir from their protocols thanks to negative results from the RECOVERY and SOLIDARITY trials.

Also read: A Good Registry Means Accountable Clinical Trials. But Does India Have One?

Poor output

Smaller trials in India have also been less accountable and have operated with little oversight.

The UKs RECOVERY trial recruited around 40,000 participants at 180 sites. The University of Oxford, which is in charge, centrally determined the protocol to follow and the outcomes to watch out for, and used new results from their own study to update their trial1. Both positive and negative results were published.

No such effort has emerged out of India for reasons including bureaucratic lethargy, little collaboration between institutions, lack of autonomy and of incentives, Dr Mathew said. Other experts also mentioned deficient institutional funding and subpar expertise.

We are a nation of band-aid action. We dont plan ahead of time.

We cant wake up in the middle of the pandemic and expect world-class research, said Dr Soumyadeep Bhaumik, co-head of the meta-research and evidence synthesis unit at the George Institute, New Delhi. A research ecosystem develops after years of systematic investment in institutions, expertise and a regulatory framework.

It was only on June 10, 2021, that the Indian Council for Medical Research issued a tender to develop a large, multicentre, adaptive trial platform like RECOVERY.

According to a researcher who worked on a prominent Centre-funded COVID-19 trial in 2020, a serious lack of expertise among participating clinicians also compounded the chronic under-investment. It took a lot of hand-holding and training to get them to appropriately complete the trial, the researcher said.

It can feel both good and bad to know that India is in fact capable of conducting well-designed trials. For example, the PLACID trial, an ICMR-funded enterprise, enrolled 464 patients (calculated to be sufficient power) from April 22 to July 14, 2020, to study the efficacy of convalescent plasma. The results were published as a preprint paper on September 10 and in BMJ a month later.

In another example, as of October 15, 2020, Indian doctors had enrolled 937 Indian participants at several hospitals in the country for the SOLIDARITY trial.

Even when large, centralised trials arent feasible, Dr Bhaumik said a set of core outcome measures could ensure small trials measuring the same things also watch out for the same results.

Here, experts deliberate on and recommend some common patient-centric outcomes for clinicians to use when designing their trials. Adopting these outcomes wouldnt render all trials the same.

They could measure other outcomes as well but using a core outcome set means the results of these small trials can be pooled to inform policy and practice, Dr Bhaumik said. We need to start developing core outcome sets for diseases of significance to our country.

In the time of COVID-19, this duty fell on the ICMRs shoulders, but which is yet to issue any such directions to the many COVID-19 trials happening in the country.

In fact, in the loudest directive the organisation sent forth (and quickly withdrew), its chief Dr Balram Bhargava demanded in July 2020 that hospitals involved in Covaxins clinical trial complete it in just two months, or face the governments music. The results of this trial are yet to be published.

Ronak Borana is a science communicator based in Mumbai. He tweets at @ronaklmno.

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COVID-19: India Has a Habit of Bad Clinical Trials - The Wire Science

Jasper Therapeutics and Aruvant Announce Research Collaboration to Study JSP191, an Antibody-Based Conditioning Agent, with ARU-1801, a Novel Gene…

Posted: at 1:52 am

REDWOOD CITY, Calif. and NEW YORK and BASEL, Switzerland, June 21, 2021 /PRNewswire/ --Jasper Therapeutics, Inc., a biotechnology company focused on hematopoietic cell transplant therapies, andAruvant Sciences, a private company focused on developing gene therapies for rare diseases, today announced that they have entered a non-exclusive research collaboration to evaluate the use of JSP191, Jasper's anti-CD117 monoclonal antibody, as a targeted, non-toxic conditioning agent with ARU-1801, Aruvant's investigational lentiviral gene therapy for sickle cell disease (SCD). The objective of the collaboration is to evaluate the use of JSP191 as an effective and more tolerable conditioning agent that can expand the number of patients who can receive ARU-1801, a potentially curative treatment for SCD.

"This research collaboration with Aruvant is the first to use a clinical-stage antibody-based conditioning agent and a novel clinical-stage gene therapy, giving this combination a clear advantage by moving beyond the harsh conditioning agents currently used for gene therapy and establishing this next-generation potentially curative treatment as a leader in sickle cell disease," said Kevin N. Heller, M.D., executive vice president, research and development of Jasper. "Our goal is to establish JSP191 as a potential new standard of care conditioning agent, broadly in autologous gene therapy and allogeneic hematopoietic stem cell transplantation."

Gene therapies and gene editing technologies generally require that a patient's own hematopoietic stem cells first be depleted from the bone marrow to facilitate the engraftment of the new, gene-modified stem cells through a process called conditioning. Other investigational gene therapies and gene editing approaches in SCD use a high-dose chemotherapy such as busulfan for the conditioning regimen, which can place patients at prolonged risk for infection and bleeding, secondary malignancy and infertility. ARU-1801 is currently the only gene therapy that has demonstrated durable efficacy using both a lower dose of chemotherapy and a different agent than busulfan with a more limited side effect profile. The Aruvant-Jasper partnership is focused on evaluating the potential of using JSP191, a highly targeted anti-CD117 (stem cell factor receptor) monoclonal antibody agent, as the foundationof a novel conditioning regimen for use in combination with ARU-1801 to further reduce the negative side effects while maintaining efficacy.

"The unique attributes of ARU-1801 enable us to bring a potentially curative one-time therapy to individuals with sickle cell disease that can be delivered in the safest way possible," said Will Chou, M.D., Aruvant chief executive officer. "By partnering with Jasper to evaluate the use of JSP191 with ARU-1801, we are one step closer to developing a next-generation definitive therapy with an even more patient-friendly conditioning regimen. We believe that this combination may be able to further expand the number of patients who can benefit from ARU-1801 in the future, including potentially those with more moderate disease."

About JSP191JSP191 is a humanized monoclonal antibody in clinical development as a conditioning agent that blocks stem cell factor receptor signaling leading to clearance of hematopoietic stem cells from bone marrow, creating an empty space for donor or gene-corrected transplanted stem cells to engraft. While hematopoietic cell transplantation can be curative for patients, its use is limited because standard high dose myeloablative conditioning is associated with severe toxicities and standard low dose conditioning has limited efficacy. To date, JSP191 has been evaluated in more than 90 healthy volunteers and patients. It is currently enrolling in two clinical trials for myelodysplastic syndromes (MDS)/acute myeloid leukemia (AML) and severe combined immunodeficiency (SCID) and expects to begin enrollment in four additional studies in 2021 for severe autoimmune disease, sickle cell disease, chronic granulomatous disease and Fanconi anemia patients undergoing hematopoietic cell transplantation.

About ARU-1801ARU-1801 is designed to address the limitations of current curative treatment options, such as low donor availability and the risk of graft-versus-host disease (GvHD) seen with allogeneic stem cell transplants. Unlike investigational gene therapies and gene editing approaches which require fully myeloablative conditioning, the unique characteristics of ARU-1801 allow it to be given with reduced intensity conditioning ("RIC"). Compared to myeloablative approaches, the lower dose chemotherapy regimen underlying RIC has the potential to reduce not only hospital length of stay, but also the risk of short- and long-term adverse events such as infection and infertility. Preliminary clinical data from the MOMENTUMstudy, an ongoing Phase 1/2 trial of ARU-1801 in patients with severe sickle cell disease, demonstrate continuing durable reductions in disease burden.

The MOMENTUM StudyAruvant is conducting the MOMENTUM study, which is evaluating ARU-1801, a one-time potentially curative investigational gene therapy for patients with SCD. This Phase 1/2 study is currently enrolling participants, and information may be found at momentumtrials.comwhich includes a patient brochure, an eligibility questionnaireand information for healthcare providers.

About Jasper TherapeuticsJasper Therapeutics is a biotechnology company focused on the development of novel curative therapies based on the biology of the hematopoietic stem cell. The company is advancing two potentially groundbreaking programs. JSP191, a first-in-class anti-CD117 monoclonal antibody, is in clinical development as a conditioning agent that clears hematopoietic stem cells from bone marrow in patients undergoing a hematopoietic cell transplantation. It is designed to enable safer and more effective curative allogeneic and autologous hematopoietic cell transplants and gene therapies. In parallel, Jasper Therapeutics is advancing its preclinical engineered hematopoietic stem cell (eHSC) platform, which is designed to overcome key limitations of allogeneic and autologous gene-edited stem cell grafts. Both innovative programs have the potential to transform the field and expand hematopoietic stem cell therapy cures to a greater number of patients with life-threatening cancers, genetic diseases and autoimmune diseases than is possible today. For more information, please visit us at jaspertherapeutics.com.

About Aruvant SciencesAruvant Sciences, part of the Roivant family of companies, is a clinical-stage biopharmaceutical company focused on developing and commercializing gene therapies for the treatment of rare diseases. The company has a talented team with extensive experience in the development, manufacturing and commercialization of gene therapy products. Aruvant has an active research program with a lead product candidate, ARU-1801, in development for individuals suffering from sickle cell disease (SCD). ARU-1801, an investigational lentiviral gene therapy, is being studied in a Phase 1/2 clinical trial, the MOMENTUM study, as a one-time potentially curative treatment for SCD. Preliminary clinical data demonstrate engraftment of ARU-1801 and amelioration of SCD is possible with one dose of reduced intensity chemotherapy. The company's second product candidate, ARU-2801, is in development to cure hypophosphatasia, a devastating, ultra-orphan disorder that affects multiple organ systems and leads to high mortality when not treated. Data from pre-clinical studies with ARU-2801 shows durable improvement in disease biomarkers and increased survival. For more information on the ongoing ARU-1801 clinical study, please visit http://www.momentumtrials.comand for more on the company, please visit http://www.aruvant.com. Follow Aruvant on Facebook, Twitter @AruvantSciencesand on Instagram @Aruvant_Sciences.

About RoivantRoivant's mission is to improve the delivery of healthcare to patients by treating every inefficiency as an opportunity. Roivant develops transformative medicines faster by building technologies and developing talent in creative ways, leveraging the Roivant platform to launch Vants nimble and focused biopharmaceutical and health technology companies. For more information, please visit http://www.roivant.com.

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SOURCE Aruvant Sciences

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Antengene Announces Fifteen Clinical Studies and Results of Selinexor to be Presented at ASCO 2021 – PRNewswire

Posted: June 6, 2021 at 1:51 am

SHANGHAI and HONG KONG, June 1, 2021 /PRNewswire/ -- Antengene Corporation Limited ("Antengene", SEHK: 6996.HK), a leading innovative biopharmaceutical company dedicated to discovering, developing and commercializing global first-in-class and/or best-in-class therapeutics in hematology and oncology, announced that fifteen studies and results of selinexor, the world's first approved oral selective inhibitor of nuclear export (SINE), will be presented at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting, taking place in a virtual format on June 4 to 8.

Selected Abstracts:

Effects of weekly selinexor, bortezomib, dexamethasone (XVd) versus standard twice weekly bortezomib and dexamethasone (Vd) on RAS-mutated previously treated multiple myeloma (MM).

Abstract #: 8027

Effects of refractory status to lenalidomide on safety and efficacy of selinexor, bortezomib, and dexamethasone (XVd) versus bortezomib and dexamethasone (Vd) in patients with previously treated multiple myeloma.

Abstract #: 8024

Survival among older patients with previously treated multiple myeloma treated with selinexor, bortezomib, and dexamethasone (XVd) in the BOSTON study.

Abstract #: 8019

Updated overall survival of eltanexor for the treatment of patients with hypomethylating agent refractory myelodysplastic syndrome.

Abstract #: e19037

Results of the phase 2 MARCH Study: Oral ATG-010 (Selinexor) plus low dosedexamethasone in Chinese patients with relapsed/refractory multiple myeloma (RRMM) previously treated with an immunomodulatory agent (IMiD) and a proteasome inhibitor (PI).

Abstract #: e20002

Oral selinexor, pomalidomide, and dexamethasone (XPd) at recommended phase 2 dose in relapsed refractory multiple myeloma (MM).

Abstract #: 8018

SIENDO/ENGOT-EN5/GOG-3055: A randomized phase 3 trial of maintenance selinexor versus placebo after combination platinum-based chemotherapy in advanced or recurrent endometrial cancer.

Abstract #: TPS5610

Open-label phase 1 study evaluating the tolerability and anti-tumor activity of selinexor and pembrolizumab in colorectal cancer.

Abstract #: e15579

A phase 1/2 study of selinexor in combination with standard of care therapy for newly diagnosed or recurrent glioblastoma.

Abstract #: TPS2071

A phase Ib/II study of selinexor in combination with imatinib in patients with advanced gastrointestinal stromal tumor (GIST): SeliGIST/GEIS-41 trial.

Abstract #: 11534

Selinexor in combination with weekly paclitaxel in patients with advanced or metastatic solid tumors: Results of an open label, single-center, multiarm phase 1b study.

Abstract #: 5565

Once weekly selinexor, carfilzomib, and dexamethasone (XKd) in carfilzomib nonrefractory multiple myeloma (MM) patients.

Abstract #: 8038

A randomized, open-label, phase 3 study of low-dose selinexor and lenalidomide (Len) versus len maintenance post autologous stem cell transplant (ASCT) for newly diagnosed multiple myeloma (NDMM): ALLG MM23, Sealand.

Abstract #: TPS8055

Molecular predictors of response to selinexor in advanced unresectable de-differentiated liposarcoma (DDLS).

Abstract #: 11509

Selinexor containing regimens in patients with multiple myeloma (MM) previously treated with anti-CD38 monoclonal antibodies (CD38 mAbs).

Abstract #: e20020

About Antengene

Antengene Corporation Limited ("Antengene", SEHK: 6996.HK) is a leading clinical-stage R&D driven biopharmaceutical company focused on innovative medicines for oncology and other life-threatening diseases. Antengene aims to provide the most advanced anti-cancer drugs to patients in the Asia Pacific Region and around the world. Since its establishment in 2017, Antengene has built a broad and expanding pipeline of clinical and pre-clinical stage assets through partnerships as well as in-house drug discovery, and obtained 15 investigational new drug (IND) approvals and submitted 5 new drug applications (NDAs) in multiple markets in Asia Pacific. Antengene's vision is to "Treat Patients Beyond Borders". Antengene is focused on and committed to addressing significant unmet medical needs by discovering, developing and commercializing first-in-class/best-in-class therapeutics.

SOURCE Antengene Corporation Limited


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Antengene Announces Fifteen Clinical Studies and Results of Selinexor to be Presented at ASCO 2021 - PRNewswire

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