On January 18, 2022 23andMe Holding Co. (Nasdaq: ME) ("23andMe"), a leading consumer genetics and therapeutics company, reported an update on its collaboration with GlaxoSmithKline plc ("GSK"). GSK has elected to exercise its option to extend the exclusive target discovery period of the ongoing collaboration with 23andMe for an additional year to July 2023 (Press release, 23andMe, JAN 18, 2022, View Source [SID1234640972]). 23andMe will receive a one-time payment of $50 million to extend the period. In addition, 23andMe has elected to take a royalty option on its joint immuno-oncology antibody collaboration program with GSK targeting CD96 (GSK6097608, a.k.a. GSK’608), currently in Phase 1 studies. GSK will be solely responsible for GSK’608’s subsequent development in later-stage clinical trials, including full development costs moving forward.

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"The collaboration with GSK has been very productive. In less than four years, under this collaboration, we have identified over 40 therapeutic programs and have advanced an immuno- oncology antibody targeting CD96 into clinical development," said Kenneth Hillan, Head of Therapeutics at 23andMe. "GSK’s decision to extend the exclusive target discovery period of our collaboration for an additional year demonstrates the enthusiasm for our collaboration and the value our database provides for identifying targets and advancing new medicines based on human genetics."

"Our collaboration with 23andMe continues to exceed expectations, with more than 40 genetically validated drug discovery programs in the GSK portfolio that were initiated under the collaboration," said John Lepore, SVP and Head of Research at GSK. "Evidence shows that genetically validated drug targets have at least double the probability of success in becoming medicines; today more than 70% of our targets in research have genetic validation. Working with 23andMe for an additional year will continue to strengthen the quality and breadth of our pipeline and reinforce GSK’s long-term focus on human genetics, the immune system and advanced technologies to discover and develop transformational new medicines for patients."

"The CD96 program is a prime example of the potential value we bring to drug discovery and development. Through our genetic validation and based on the Phase 1a data, we are hopeful that targeting CD96 will have the potential to provide cancer patients with a new medicine in the fight against cancer," states Hillan. "We believe GSK is in the best position to move this program forward because of its leading portfolio of antibodies targeting the CD96 axis, and their ability to conduct the complex clinical studies of combination therapies that the development plan will require. This decision also allows 23andMe to strategically invest capital and resources into advancing our diverse portfolio of therapeutic programs."

23andMe’s Therapeutics team was established in 2015 with the goal to improve the way drug discovery is currently conducted by starting with human genetic information. With approximately 12 million genotyped customers, of which approximately 80 percent consent to research, 23andMe has the world’s largest set of genotypic information paired with billions of phenotypic data points contributed by engaged research participants.

About the GSK and 23andMe Collaboration
In July 2018, GSK and 23andMe entered into a collaboration which included an initial four-year exclusive target discovery period, with GSK having the option to extend that period for a fifth year. In order to jointly discover novel targets for drug development, 23andMe performs proprietary statistical analysis in-house using de-identified data from 23andMe’s consenting research participants. Together 23andMe and GSK review the summary results that can be used to progress new medicines into development. GSK and 23andMe collaborate, using their combined resources, to identify new targets and prioritize them based on the strength of the biological hypothesis, possibility to find a medicine, and clinical opportunity and progress programs to generate lead compounds, perform preclinical research and progress into clinical development.

For joint projects, program costs and profits in relevant territories (US, UK and EU) are split (50% / 50%), with each company having certain rights to opt-out of further funding or reduce its funding share for any joint collaboration program at certain defined development milestones. The company that opts out of the cost/profit split is eligible to receive a worldwide royalty, or in the case of reduced funding, an adjusted percentage of profits or royalty outside the relevant territories, if the program is successfully commercialized.

Additionally, GSK made a $300M equity investment in 23andMe, Inc. in 2018.

About the CD96 Program
The CD96 program is an immuno-oncology therapeutic mAb targeting CD96 called GSK’608. CD96 sequesters a shared ligand, CD155, away from the costimulatory receptor, CD226, effectively attenuating T and NK cell antitumor immune responses. By blocking CD96, GSK’608 may allow activation of CD226 and enhance anti-tumor immunity through T and NK cells.

GSK’608 is now being dosed in combination with GSK’s PD-1 blocking drug, dostarlimab, in a Phase 1 clinical trial. Additional studies will potentially also involve combinations with other anticancer treatments, such as anti-TIGIT and anti-PVRIG drugs.

Prior to taking the worldwide royalty election, the CD96 program was advanced under a 50/50 cost share and a profit share arrangement between 23andMe and GSK in the shared territories of US, UK and EU with a tiered royalty for other territories. With the worldwide royalty option, 23andMe will be eligible to earn tiered worldwide royalties up to the low double digits if GSK’608 is successfully brought to market. This option allows 23andMe to retain economic upside if GSK’608 is successfully brought to market but will no longer be contributing to the development costs as the program advances into later, larger and more complex clinical studies. This allows 23andMe to invest further in its advancing pipeline of therapeutic programs, largely identified under the GSK collaboration. In addition, if GSK’608 is successful in achieving market authorization, 23andMe will not be required to contribute to marketing and commercialization costs.

R&D Day Event Information
To discuss the GSK collaboration updates and other developments from its Therapeutics and Consumer groups in more detail, the company is hosting a virtual R&D Day event today from 8:00 a.m. to 11:30 am Pacific Time. The webcast event can be accessed at View Source A webcast replay will be available at the same address for a limited time within 24 hours after the event.

On January 18, 2022 Race Oncology Limited ("Race") reported that it has received a $707,557 Research & Development Tax Incentive Refund from the Australian Taxation Office for the financial year ending 30 June 2021 (Press release, Race Oncology, JAN 18, 2022, View Source [SID1234609999]).

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Race’s Managing Director and CEO, Mr Phil Lynch commented: "The increased refund for FY21 is representative of the enhanced investment we made into R&D as we expanded our Zantrene clinical and supporting programs. We remain grateful recipients of the Australian R&D tax incentive, which is an important source of funding for Race and one that encourages us to keep our research and development work in Australia."

Receipt of the R&D tax incentive will be added to the Company’s cash balance and reported in Appendix 4C quarterly cash flow report for the March quarter.

On January 18, 2022 Global Coalition for Adaptive Research (GCAR) reported an update on the progress of GBM AGILE (Glioblastoma Adaptive Global Innovative Learning Environment – NCT03970447) (Press release, , 18 18, 2022, View Source [SID1234605657]). GBM AGILE is a revolutionary patient-centered, adaptive platform trial for registration that tests multiple therapies for patients with newly-diagnosed and recurrent glioblastoma (GBM) – the deadliest form of brain cancer.

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Key updates

As of January 2022, GBM AGILE has screened over 1000 patients. Enrollment rates are 3 to 4 times greater than traditional GBM studies, with active sites averaging 0.75 to 1 patients/site/month.
With the active enrollment, Biohaven Pharmaceutical Holding Company Ltd.’s (NYSE: BHVN) troriluzole and Vigeo Therapeutics’ VT1021 have been selected to participate in GBM AGILE with anticipated commencement of recruitment in Q1 2022. They will be evaluated in all patient subgroups of the trial which include newly-diagnosed methylated MGMT, newly-diagnosed unmethylated MGMT, and recurrent GBM.
Biohaven’s troriluzole and Vigeo’s VT1021 will be the fourth and fifth arms to join the trial, respectively. GBM AGILE allows multiple drugs from different pharmaceutical companies to be evaluated simultaneously and/or over time against a common standard of care control.
GBM AGILE recently received IND approval in China for the evaluation of Kazia’s paxalisib. Study start up activities in China have commenced with site openings planned for Q2/Q3 2022.
GBM AGILE continues to expand its global access, with plans to open Europe including sites in Austria, France, Germany, Italy, and Switzerland in early 2022. Additional regions globally are being assessed.
GBM AGILE is an international, innovative platform trial designed to more rapidly identify and confirm effective therapies for patients with glioblastoma through response adaptive randomization and a seamless phase 2/3 design. The trial, conceived by over 130 key opinion leaders, is conducted under a master protocol, allowing multiple therapies or combinations of therapies from different pharmaceutical partners to be evaluated simultaneously. With its innovative design and efficient operational infrastructure, data from GBM AGILE can be used as the foundation for a new drug application (NDA) and biologics license application (BLA) submissions and registrations to the FDA and other health authorities.

Biohaven’s troriluzole is a novel, orally administered small molecule that modulates glutamate, the most abundant excitatory neurotransmitter in the human body. Troriluzole is thought to restore glutamate homeostasis by enhancing glutamate cycling, decreasing presynaptic glutamate release, and augmenting the expression and function of excitatory amino acid transporters (i.e., EAAT2) located on glial cells that play a key role in clearing excess glutamate from the synapse. Troriluzole was selected for inclusion in GBM AGILE, based on compelling evidence showing deregulation of glutamate in glioblastoma. The therapeutic potential of troriluzole in glioblastoma and other oncology indications is supported by several recent clinical and translational research studies conducted with troriluzole and its active moiety.

Dr. Michael Lim, Chair of the Department of Neurosurgery at Stanford University and Dr. Michael Weller, Director Department of Neurology, University Hospital Zurich, Switzerland have been selected to serve as arm Principal Investigators for troriluzole’s evaluation in GBM AGILE.

Vigeo’s VT1021, is a first-in-class dual modulating compound that blocks the CD47 immune checkpoint and activates the apoptotic and macrophage reprogramming activity of CD36. The result of the dual modulating activity is the induction of apoptosis in tumor and endothelial cells, as well as an increase in both CTL:Treg and M1:M2 macrophage ratio. The biological/therapeutic activity of VT1021 is mediated by the stimulation of thrombospondin-1 (Tsp-1). Through these dual-modulating effects VT1021 reprograms the tumor microenvironment from one that is immune suppressive, or "cold," to immune enhanced (or sensitized), or "hot," that are more susceptible to attack from the immune system. With its novel mechanism of action and clinical data from a Phase 2 expansion study in recurrent GBM patients, VT1021 is undergoing further studies to determine its effect in treating the disease, given that CD36 and CD47 are found to be highly expressed in tumor cells compared to normal brain tissue. Vigeo is developing VT1021 as a therapeutic agent across a range of cancers, with a current focus on solid tumors.

VT1021 will be led by arm Principal Investigators, Dr. Howard Colman, Professor, Huntsman Cancer Institute and Department of Neurosurgery, University of Utah, and Dr. Tom Mikkelsen, Medical Director, Henry Ford Precision Medicine Program & Clinical Trials.

The opening of study locations in Europe is anticipated to occur in early 2022 with sites planned in Austria, France, Germany, Italy, and Switzerland. Dr. Michael Weller, Director Department of Neurology, University Hospital Zurich, is serving as regional Principal Investigator of Europe.

"We are excited about the many achievements of GBM AGILE over the last 2.5 years since its launch," said Meredith Buxton, CEO, GCAR. "As an innovative collaboration between academic investigators, patient organizations and industry, GBM AGILE serves as a model for more efficient, cost-effective, and accelerated drug development. While we are encouraged by our accomplishments to date, we know have a lot more work to do to help identify and confirm new drugs for approval to support patients with GBM and their families. We are optimistic that GBM AGILE will provide important information to accelerate the evaluation of new treatments and may identify new and improved options for patients."

On January 18, 2022 Cosette Pharmaceuticals, Inc., a New Jersey-based specialty pharmaceutical company, reported that it has closed a transaction to acquire the US sales and distribution rights to eight branded commercial products from leading Japanese pharmaceutical company, Daiichi Sankyo Company, Ltd (4568:JP) and affiliates (Press release, Cosette Pharmaceuticals, 18 18, 2022, https://www.businesswire.com/news/home/20220118005370/en/%C2%A0Cosette-Pharmaceuticals-Acquires-Rights-to-Eight-Branded-Products-from-Daiichi-Sankyo [SID1234605656]). The transaction adds eight prescription products focused on cardiovascular indications to Cosette’s current portfolio of over forty-five commercial products:

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BENICAR (olmesartan medoxomil)
BENICAR HCT (olmesartan medoxomil/hydrochlorothiazide)
WELCHOL (colesevelam HCL) tablets
WELCHOL (colesevelam HCL) Oral Suspension
AZOR (amlodipine/olmesartan medoxomil)
TRIBENZOR (olmesartan medoxomil/amlodipine/hydrochlorothiazide)
EFFIENT (prasugrel)
EVOXAC (cevimeline HCL)
"This transformative acquisition represents a significant expansion and diversification of Cosette’s portfolio and business," said Apurva Saraf, Cosette’s President and CEO. "We look forward to build on this transaction and successfully acquire and integrate important product portfolios in the future, and to continue to make these critical medications available for patients and prescribers."

"As part of our 2030 vision of becoming a global top 10 leader in oncology, we are shifting our structure to focus on our oncology portfolio in the U.S., while ensuring these legacy medicines continue to be available to the patients who rely on them," said Ken Keller, President & CEO, Daiichi Sankyo, Inc. "We are proud and thankful of the effort by our teams at Daiichi Sankyo for their dedication to patients and their providers and look forward to a smooth transition with Cosette."

The agreement outlines a 30-month transition period during which Daiichi Sankyo and Cosette Pharmaceuticals will transfer responsibilities for the manufacture, supply and commercialization of these products, including quality assurance, pharmacovigilance and regulatory matters.

According to IQVIA, U.S. annual sales for the acquired products for the 12 months ended November 2021 were approximately $123 million. No financial details will be disclosed.

Products:

Please see Package Insert (PI) for full prescribing information including complete safety information:

BENICAR (olmesartan medoxomil) See full prescribing information including boxed warning regarding fetal toxicity
BENICAR HCT (olmesartan medoxomil/hydrochlorothiazide) See full prescribing information including boxed warning regarding fetal toxicity
WELCHOL (colesevelam HCI) Tablets See full prescribing information
WELCHOL (colesevelam HCI) Oral Suspension See full prescribing information
AZOR (amlodipine/olmesartan medoxomil) See full prescribing information including boxed warning regarding fetal toxicity
TRIBENZOR (olmesartan medoxomil/amlodipine/hydrochlorothiazide) See full prescribing Information including boxed warning regarding fetal toxicity
EFFIENT (prasugrel) See full prescribing Information, including boxed warning regarding bleeding risk, and medication guide.
EVOXAC (cevimeline HCI) See full prescribing Information
Advisors

Morgan Lewis & Bockius LLP served as legal counsel and BofA Securities served as exclusive financial advisor to Cosette Pharmaceuticals. Goldman Sachs & Co. LLC served as exclusive financial advisor to Daiichi Sankyo.

On January 18, 2021 City of Hope, a world-renowned cancer research and treatment organization, and CytoImmune Therapeutics, a clinical-stage immunotherapy company that is developing a novel class of natural killer (NK) cell-based cancer therapies, reported a study published in the high-impact journal Gastroenterology that demonstrates off-the-shelf anti-prostate stem cell antigen (PSCA) chimeric antigen receptor (CAR) NK cells significantly suppressed pancreatic cancer in vitro and in vivo using a method known as freeze-thaw (Press release, City of Hope, 18 18, 2022, View Source [SID1234605655]).

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The therapy — PSCA CAR_s15 NK cells, also known as CYTO NK-203 — persisted more than 90 days after infusion and significantly prolonged the survival of mice with pancreatic cancer, showing that the freeze-thaw method works. For the study, PSCA CAR_s15 NK cells were produced and then frozen. The cells were then thawed and used in preclinical studies at City of Hope.

"Our patients need additional ways to attack their pancreatic cancer. The work presented by City of Hope’s team is distinctive and promising for two reasons: First of all, it is based on a precision medicine approach that is a special target in the patient’s pancreatic cancer — PSCA. Secondly, it is an immunologic approach, using human natural killer cells, which are specifically engineered to attack the patient’s cancer. These findings should be accelerated to a clinical trial as rapidly as possible," said Daniel D. Von Hoff, M.D., a distinguished professor in the Molecular Medicine Division of the Translational Genomics Research Institute (TGen), an affiliate of City of Hope. He also is senior consultant-clinical investigator at City of Hope and is one of the nation’s leading authorities on the treatment and care of pancreatic cancer patients.

"City of Hope is committed to finding more effective and innovative treatments for difficult-to-treat solid cancers, and pancreatic cancer is clearly one of them," said Saul Priceman, Ph.D., assistant professor in the Department of Hematology & Hematopoietic Cell Transplantation at City of Hope and a study author. "These new PSCA CAR_s15 NK cell preclinical studies provide tremendous support for the anticipated upcoming clinical trials to evaluate efficacy and safety of this novel CAR-engineered NK cell therapy in patients with pancreatic cancer, which is a promising expansion of our existing clinical programs that target PSCA in solid cancers using CAR-engineered T cell therapy."

Pancreatic cancer is the third leading cause of cancer-related death in the United States with a five-year survival rate of approximately 10%. The cancer is typically detected when it is at a late stage and incurable. Chemotherapy or other therapies provide modest benefit. Therefore, the development of new therapies for pancreatic cancer is crucial. The therapy can also be used for other PSCA+ cancers, such as stomach and prostate.

NK cell technology works by using natural killer cells from a patient or donor. NK cells are then engineered so they express a receptor — a CAR — that is specific for a protein expressed by cancerous cells, along with the secretion of IL-15, which sustains the survival of the NK cells.

Christina Coughlin, M.D., CEO of CytoImmune Therapeutics, said, "We are excited to share this data on our CAR NK candidate for pancreatic cancer. This foundational data supports robust anti-tumor activity with CYTO NK-203, making us confident our innovative and off-the-shelf NK cell therapy approach has the potential to deliver more accessible, safe and effective cell-based treatment options to cancer patients. We are encouraged by these findings and look forward to continuing our work with City of Hope in order to move this initiative to the clinic."

This immunotherapy is revolutionizing the treatment of some blood cancers; however, its use in the treatment of solid tumors has been limited, in part because most of the proteins currently used to target CAR cells to solid tumors are present in low levels on other normal tissues, leading to toxic side effects.

Based on research by Michael Caligiuri, M.D., president of City of Hope National Medical Center and the Deana and Steve Campbell Physician-in-Chief Distinguished Chair, and Jianhua Yu, Ph.D., professor and director of the Natural Killer Cell Biology Research Program, who have nearly 55 years of collective laboratory investigation of NK cells, CytoImmune is developing an NK cell platform designed to overcome the limitations and challenges of current technologies for engineering NK cells. The platform is designed to generate an abundant supply of CAR NK cells from a single umbilical cord donor, engineered with the CAR for effective recognition of tumor targets, and secreting IL-15 to improve the persistence of CAR NK cells for sustained activity in the body. The process enables scientists to freeze, transport and store engineered CAR NK cells for off-the-shelf use for the treatment of cancer.

The study titled "Off-the-shelf PSCA-directed chimeric antigen receptor natural killer cell therapy to treat pancreatic cancer" can be found here.