On January 18, 2022 Zetagen Therapeutics, a private, clinical-stage, biopharmaceutical company dedicated to driving breakthrough innovation in the treatment of metastatic bone cancers and osteologic interventions, reported it has received authorization from Health Canada to conduct a Phase 2a study, examining the safety and efficacy of ZetaMet (Zeta-BC-003) for the treatment of metastatic bone lesions (Press release, Zetagen Therapeutics, JAN 18, 2022, View Source [SID1234643707]).

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"The start of this study marks a critical point in the development of ZetaMet (Zeta-BC-003)," said Bryan Margulies, PhD, chief scientific officer of Zetagen Therapeutics. "So far, our combination technology has, in preclinical studies, demonstrated its ability to resolve existing metastatic bone lesions, inhibit pain and stimulate targeted bone regeneration. Now, our goal is to prove this outcome in human application."

ZetaMet (Zeta-BC-003) works through a mechanism of action (MOA) which is a novel and patented molecular pathway. The small molecule, precisely-dosed, delivered to the affected area through a proprietary drug-eluting carrier, stimulates stem cells, activating cells to grow healthy bone known as "osteoblasts", and inhibits cells associated with bone degradation called "osteoclasts".

"We know that bone metastases are common among late-stage cancer patients and the pain associated with them is debilitating," said Joe C. Loy, CEO of Zetagen Therapeutics. "We look forward to this important next step in the development of ZetaMet (Zeta-BC-003) which, if successful, will bring this novel therapy one step closer to a reality for patients who need it most."

Bone metastases occur when cells from the primary cancerous tumor relocate to the bone. When these cancers relocate, they can cause changes to the bone, damaging it in a process called osteolysis. Osteolysis can cause small holes within the bone, weakening it and increasing the risk of breakage. These holes are called "lytic lesions." Among cancers which metastasize to bone, Breast and Prostate are most prevalent, amounting to approximately 70-percent of cases.[1]

The Phase 2a study will be conducted at a single site in partnership with McGill University, Montreal, Quebec. The study will enroll 10, Stage 4 breast cancer patients, pre-radiation, who present with lytic lesions created by metastatic tumors in their spinal column. The year-long study is scheduled to be completed by Q1 2023.

On January 18, 2022 StarkAge Therapeutics, a pioneering discovery-stage biotechnology company focusing on cellular senescence related diseases, reported it received Bpifrance Deeptech label designation for its lead program in Idiopathic Pulmonary Fibrosis (IPF) (Press release, StarkAge Therapeutics, JAN 18, 2022, View Source [SID1234641094]).

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"This exceptional achievement, under the scientific leadership of Dr. Müge Ogrunc, underscores the potential of the technology we are developing." said Dr. Thierry Mathieu founder and President of StarkAge Therapeutics. "We are grateful for the strong and continuous support from Bpifrance since the creation of StarkAge Therapeutics".

With this label, StarkAge Tx was awarded 2€ million in non-dilutive funding, the maximum allowed per project in this program1, across 4 years. This is a major steppingstone to advance and drive their program to success.

A further increase in capital will likely be required to fully fund their pre-clinical IPF program prior to engaging with US and European regulatory agencies.

"This will help us move our research forward significantly" added Dr. Mathieu. "IPF is the first program we are testing with ExoCiseTM, our cellular senescence biomarker platform. If successfully completed, it could lead to helping with many other age-related diseases."

StarkAge Therapeutics also announced that Dr. Pierre-Michel Bringer, has been appointed Chief Executive Officer. Dr. Bringer has over 35 years of Pharmaceutical Industry experience in multiple countries including the US, spanning M&A / licensing, communication, strategic planning, marketing & sales. Most recently he served 13 years as Investor Relations Officer with Novartis. Pierre-Michel holds a Doctorate of Pharmacy from Paris University

"Pierre-Michel broad industry knowledge, including expertise with investors, and his passion for science make him the strong leader we needed" said Dr. Mathieu "We are thrilled to have Pierre-Michel with us as CEO, and I am happy to hand-over the helm of StarkAge Therapeutics".

"I feel honored and humbled to lead the next steps of StarkAge Therapeutics whose science focuses on harnessing immunotherapy against cellular senescence." said Dr. Bringer.

About senescence
Cellular senescence is a stress-induced, durable cell-cycle arrest of previously replication-competent cells. Senescent cells can be beneficial as well as detrimental regarding host physiology and disease. Indeed, while cellular senescence can facilitate physiological processes such as tissue repair and wound healing, the actions of their secreted pro-inflammatory cytokines can promote tissue dysfunctions, especially during aging. In this context, the rate at which senescent cells accumulate within tissues increases with aging leading to age-related disorders causing diseases such as idiopathic pulmonary fibrosis2,3 (IPF) and many others4,5,6,7. Consequently, these detrimental senescent cells are considered a potential therapeutic target in age-related disorders. Nevertheless, the challenge remains to specifically target detrimental senescent cells while avoiding altering the functions of beneficial ones.

About Bpifrance Deeptech program
Bpifrance’s Deeptech program1 aims to help finance well-characterized and disruptive R&D programs.

The DeepTech label is granted to projects based on innovative technology, in particular:

from a research laboratory (public/private) and/or relying on a team/governance in connection with the scientific world
which constitute a strongly differentiating advantage compared to the competition
characterized by a long/complex go-to-market (development, industrialization, marketing) and therefore probably capital-intensive.
About ExoCiseTM
ExoCise is StarkAge Therapeutics’ proprietary platform designed to analyze extracellular vesicles (EVs), particularly exosomes and microvesicles, identifying robust and specific biomarkers for senescent cells in disease-setting by their specific multi-OMICs8 characterization.

EVs are secreted by virtually all cell types in the body and released in body fluids, particularly blood. EVs contain various molecules such as RNA, proteins, enzymes, cytokines etc. Some of these molecules are specific to the tissue they originate from, and even specific to certain cells within that tissue (biomarkers). EVs secreted from diseased or senescent cells to the blood could be used to detect and diagnose such conditions with a simple blood draw.

By applying ExoCise to patients with age-related diseases involving senescent cell accumulation, StarkAge Therapeutics expects to design safe and targeted immunotherapy solutions, setting StarkAge Therapeutics apart from competitors’ approaches with senolytic drugs which lacked safety and selectivity.

About Idiopathic Pulmonary Fibrosis (IPF)
IPF is a severe and debilitating disease with limited-or-no therapeutic options, in which the lungs become fibrotic and scarred9. It is a progressive illness where breathing becomes increasingly difficult over time until patients die from IPF. There is currently no treatment that can stop the evolution of the disease, or even reverse the scarring of the lungs.

IPF prevalence10 is estimated between 14 and 27.9 cases per 100,000 habitants in the US, in Europe 1.25 to 23.4 cases per 100,000 habitants in Europe.

With regard to IPF life expectancy11, the estimated mean survival is 2-5 years from the time of diagnosis. Estimated mortality rates are 64.3 deaths per million in men and 58.4 deaths per million in women.

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."