BRD9

NEW YORK, June 03, 2024 (GLOBE NEWSWIRE) -- RUMI Scientific, Inc. (“RUMI”) a developer of therapies for rare and neurodegenerative diseases using its high throughput organoid phenotypic screening platform, today announced it has received a Phase II Small Business Innovation Research (SBIR) grant from the National Institutes of Mental Health totaling $1.9 MM. RUMI’s organoid platform utilizes an unbiased phenotypic approach to target drug discovery for CNS and other diseases. In addition to its lead candidate in preclinical development for Huntington’s disease, Rumi is leveraging its platform to identify potential new therapeutic approaches aimed at treating various genetic forms of autism and peripheral diseases such as chronic kidney disease. The Phase II award will fund RUMI’s ongoing work to model later stages of brain development relevant to developing therapeutics for autism and other neurological disorders. The grant funding, the first Phase II SBIR award the Company has received since its inception, focuses on the development of an in vitro tool to mimic physiological and pathological neuronal networks of forebrain neurons termed cerebroids. The project brings together an interdisciplinary team to develop an innovative solution that will accelerate the discovery of new therapeutic candidates for autism, which has seen limited innovation despite remaining an area of major unmet medical need. To-date, the Company has received a total of more than $4 million in non-dilutive technology and grant funding. “This grant funding is an important milestone in the continued evolution of RUMI and will jumpstart our discovery and development efforts in autism,” said Allen Fienberg, PhD, Chief Executive Officer of RUMI. “We are continuing to advance our lead program, an orally-administered BRD9 inhibitor for Huntington’s Disease, toward clinical development and look forward to expanding our CNS efforts to include work in the autism space as a result of this non-dilutive capital.” About Rumi ScientificRumi Scientific’s mission is to identify and develop novel therapeutics for rare and neurodegenerative diseases by employing its revolutionary synthetic human tissue platform to produce more predictive data leading to a safe and faster clinical trial process. The Company’s lead program is an orally available bromodomain-containing protein 9 (BRD9) inhibitor in lead optimization for the treatment of Huntington’s disease. Founded in 2016, Rumi licensed foundational technology from The Rockefeller University developed by co-founders Ali H. Brivanlou, Ph.D., and Eric D. Siggia, Ph.D. For more information on Rumi Scientific, please see www.rumiscientific.com or contact info@rumiscientific.com. Rumi Scientific:Allen Fienberg, Ph.D.Chief Executive Officerallen@rumiscientific.com Fred Etoc, Ph.D.Chief Scientific Officerfred@rumiscientific.com

PRESS RELEASE Amphista Therapeutics unveils new differentiated mechanism of action for BRD9 degradation at 2024 Protein Degradation in Focus Symposium First presentation of a novel mechanism of action for the degradation of BRD9 – completely differentiated from cereblon- or VHL-based PROTACs Amphista’s bifunctional BRD9 degraders selectively induce BRD9 to DCAF16 proximity and serve as molecular glues, leading to strong and rapid degradation of BRD9 Discovery further underscores Amphista’s proprietary chemistry and high-quality science which is being applied to the discovery and development of additional targeted glues beyond BRD9 Cambridge, UK, May 23, 2024 – Amphista Therapeutics (“Amphista”), a leader in next generation targeted protein degradation (TPD) approaches, today announces the unveiling of a new mechanism of action for the degradation of BRD9, an emerging target in oncology, that is differentiated from cereblon- or VHL-based PROTACs, during an oral presentation at the 2024 Protein Degradation in Focus Symposium held in Dundee, UK. This significant news for the TPD field builds upon an earlier announcement by Amphista of two compelling data sets demonstrating in vivo efficacy and central nervous system (CNS) activity of its mechanistically differentiated protein degraders. At today’s presentation titled “Degradation of BRD9 by a novel targeted glue”, Dr Andrea Testa, Scientific Co-Founder and Senior Director, Discovery Chemistry showed data from proteomic and genetic validation studies which demonstrate that Amphista’s bifunctional degraders induced degradation of BRD9 by target-assisted E3 ligase recruitment. This novel mechanism selectively induces the proximity of BRD9 to DCAF16 and serves as a molecular glue. DCAF16 is a cullin-RING E3 ligase which can facilitate degradation of proteins of interest via ternary complex formation. Induction of this complex leads to deep and rapid degradation of BRD9 in vivo. Louise Modis, Chief Scientific Officer of Amphista Therapeutics, said: “The discovery of a novel mechanism for BRD9 degradation, differentiated from cereblon- or VHL-based PROTACs, is a testament to Amphista’s proprietary chemistry and know-how. Our ability to translate this novel approach into high-quality, drug-like compounds with oral bioavailability and activity in vivo is truly exciting. As we continue to spearhead our efforts to advance new TPD approaches, our goal remains clear – to expand the offering of TPD medicines beyond CRBN and VHL-based agents and bring effective treatments to patients in areas of high unmet need.” In the results presented, Amphista’s sub-nanomolar BRD9 degraders showed activity in both solid and liquid cancer cell lines and demonstrated a high degree of selectivity over 8,000 proteins quantified by proteomics, including the closely related proteins BRD7 and BRD4. Notably, these compounds induced BRD9 degradation in a mouse xenograft model illustrating Amphista’s BRD9 degraders are orally bioavailable and active in vivo. This is the first-time in vivo degradation of BRD9 has been demonstrated via DCAF16, underscoring the potential therapeutic application of Amphista’s bifunctional degraders. Building on this knowledge, Amphista is applying its proprietary scientific know-how and expertise to the development of targeted glues which induce degradation of different targets, expanding the opportunity beyond BRD9. Future announcements will provide details of additional pipeline targets as part of Amphista’s ambitions to develop a first- and/or best-in-class portfolio of degraders with leading physicochemical properties. About Amphista Therapeutics Amphista Therapeutics is focused on transforming the lives of patients with severe diseases, including cancer and neurodegenerative disease, through the advancement of next generation targeted protein degradation (TPD) medicines. Amphista is applying its proprietary warhead chemistry and mechanistic know-how to generate bifunctional targeted glues with a differentiated mechanism and leading physicochemical properties. Its portfolio offers the potential for first- and/or best-in-class assets and expanding the offering of TPD medicines beyond CRBN and VHL-based agents. Founded by Advent Life Sciences, Amphista is a spin-out of TPD expert Professor Alessio Ciulli’s laboratories at the University of Dundee. Amphista is funded by leading life science investors including Forbion, Gilde Healthcare, Novartis Venture Fund, Advent Life Sciences, Eli Lilly & Company and The Dementia Discovery Fund, and also has strategic collaborations with Bristol Myers Squibb and Merck. For more information, please visit: Amphista and the Amphista logo are all trademarks or registered trademarks of Amphista Therapeutics Limited. For more information please contact: ICR Consilium Amber Fennell, Namrata Taak Email: Amphista@consilium-comms.com Tel: +44 (0)20 3709 5813

Merck KGaA is now the fourth Big Pharma to sign on to a collaboration with C4 Therapeutics. Apparently, C4 Therapeutics' protein degradation tech brings all the Mercks to the yard. The Massachusetts biotech has signed on Merck KGaA in a $740 million biobucks partnership to find two degraders for cancer.  Merck KGaA is offering $16 million upfront and $740 million in biobucks for the two degraders aimed at proteins that drive cancer growth. Merck will pay for C4’s discovery work and be responsible for future clinical development, according to Monday's announcement. C4 also stands to make mid single- to low double-digit royalties should any of the targets turn into marketed drugs.  Paul Lyne, head of Merck KGaA’s oncology research unit, said the deal adds more depth to the company’s protein degradation investments.  The deal comes less than three months after Merck & Co. inked a research partnership with C4 of its own, paying $10 million upfront and more than $600 million in biobucks for the smaller company to develop an exclusive degrader-antibody conjugate (DAC). The New Jersey Merck has the option to license three additional DACs, which would push the value of the deal to $2.5 billion.  C4 has now inked collaborations with four Big Pharmas, with Biogen and Roche also tied up in collaborations with the company.  But despite the business development momentum, C4 has had a bumpy few months. The company announced layoffs to 30% of the team in January, impacting some 45 employees. That move came two months after C4 halted development on CFT8634, a small molecule for which degrading the BRD9 protein did not seem to translate to efficacy in patients with cancer.  Instead, C4 is prioritizing two other clinical stage assets: CFT7455 and CFT1946. The former is an IKZF1/3 degrader being tested in patients with multiple myeloma and non-Hodgkin lymphoma, while CFT1946 is aimed at patients with BRAF V600-mutated solid tumors.  C4 spent virtually the exact amount on R&D in 2023 as it did in 2022, according to the company's fourth-quarter earnings report, citing lower preclinical costs but higher clinical-stage costs. The biotech still reported a sizable $282 million in cash on hand as of the end of the year.