TRPML1

Advancing a deep pipeline of therapeutics focused on treating neurological, cardiometabolic, and ophthalmic diseases Led by expert R&D leadership team with proven ability to develop therapies for CNS and peripheral diseases ARCH Venture Partners, F-Prime Capital, and Mubadala Capital lead $200 million investment to fuel acceleration of Tenvie into a multi-clinical asset company SOUTH SAN FRANCISCO, Calif., Jan. 08, 2025 (GLOBE NEWSWIRE) -- Tenvie Therapeutics launched today with a commitment to transform the treatment of neurological diseases. The company combines a deep and diverse portfolio of small molecule assets, including programs acquired from Denali Therapeutics Inc., with a proven team of research and development leaders. The $200 million in funding led by ARCH Venture Partners, F-Prime Capital, Mubadala Capital, with participation from additional high-quality investors, will accelerate Tenvie’s growth into a multi-clinical asset company. “Tenvie was founded to fundamentally alter the treatment paradigm for neurological diseases and profoundly impact the lives of patients, their families, and caregivers,” said Tony Estrada, Ph.D., President and Chief Scientific Officer at Tenvie. “Our team’s validated approach uniquely allows us to access the brain while enabling the parallel development of precision-designed peripherally-restricted small molecules to address a broad array of diseases.” Tenvie is developing a portfolio of wholly owned, highly brain-penetrant and peripherally restricted small molecules that address three key drivers of disease: resolving inflammation, rescuing metabolic dysfunction, and restoring lysosomal function. Its most advanced programs, an NLRP3 inhibitor and an allosteric SARM1 inhibitor, are in the IND-enabling stage. Tenvie’s diverse pipeline also includes programs focused on neuroprotective pathways, including TRPML1 and TMEM175. “Tenvie was purpose-built to apply deep biological and chemical insights to address critical disease pathways,” said Paul L. Berns, Managing Director at ARCH Venture Partners and Executive Chair of Tenvie. “Tenvie’s promise is to unlock the therapeutic potential of small molecules to address key drivers of both central and peripheral diseases.” Tenvie has assembled a team of experts across neurology and CNS drug development, small molecule chemistry, neurobiology, translational medicine, and business operations. The company’s leadership team and Board of Directors includes: Tony Estrada, Ph.D., President, Chief Scientific Officer and Board DirectorBrian Cuneo, J.D., Chief Business and Legal OfficerTanya Fischer, M.D., Ph.D., Chief Medical OfficerPaul L. Berns, Executive Chair of Tenvie’s Board, Managing Director, ARCH Venture PartnersKristina Burow, Tenvie Board Director, Managing Director, ARCH Venture PartnersAlaa Halawa, Tenvie Board Director, Head of Healthcare and Executive Director, Mubadala CapitalJoe Lewcock, Ph.D., Tenvie Board Director, Chief Scientific Officer, Denali TherapeuticsStacie Weninger, Ph.D., Tenvie Board Director, President, FBRI, Venture Partner, F-Prime Capital “There remains an urgent need for neurological treatments that provide durable therapeutic benefit and fill the gaps in care for diseases with limited or no effective therapies,” said Stacie Weninger, Venture Partner at F-Prime Capital. “Led by CNS drug developers with proven track records in advancing molecules from discovery to clinical validation, Tenvie is set to lead the next generation of neurology treatments.” About Tenvie Therapeutics Tenvie is a biotechnology company committed to engineering small molecules that transform the treatment of neurological diseases. The company’s foundation is purpose-built with a diverse portfolio of small molecules and a proven team of CNS drug developers to rapidly deliver multiple clinical assets. Tenvie is advancing a pipeline of therapeutics focused on treating neurological, cardiometabolic, and ophthalmic diseases. Its portfolio of wholly owned, highly brain-penetrant, and precision-designed peripherally restricted small molecules address three key drivers of disease: resolving inflammation, rescuing metabolic dysfunction, and restoring lysosomal function. The company’s most advanced programs target NLRP3 and SARM1, with additional programs in preclinical development. For more information, please visit www.tenvie.com and follow the company on LinkedIn. Contacts: Monique Allaire, THRUST monique@thrustsc.com Carly Scaduto, Carly Scaduto Consultingcarly@carlyscadutoconsulting.com

A new startup has emerged with $200 million and access to multiple preclinical drug candidates from neuroscience drugmaker Denali Therapeutics. On Wednesday morning, South San Francisco-based Tenvie Therapeutics unveiled a large launch round from ARCH Venture Partners, F-Prime Capital, Mubadala Capital and other undisclosed investors. The biotech was originally formed last March as NICO Therapeutics and is developing brain-penetrant, peripherally restricted small molecules. As Tenvie, it is advancing a suite of preclinical programs that were formerly under the wings of Denali, a CNS drug developer with accelerated approval hopes in Hunter syndrome, but has experienced multiple clinical setbacks in recent years alone and with partners Sanofi , Takeda and Biogen . Tenvie declined to disclose how much it paid for the transactions with Denali. A Denali spokesperson said the company is eligible to receive an undisclosed amount of biobucks and royalties, plus it has an equity stake in Tenvie. Its chief scientific officer Joe Lewcock is also on the Tenvie board. An NLRP3 inhibitor and an allosteric SARM1 inhibitor are at the IND-enabling stage, the company said. Further behind, it has pipeline projects focused on TRPML1 and TMEM175. The startup is led by former Denali SVP and head of discovery sciences Tony Estrada. He serves as president and chief scientific officer of Tenvie, which has about 35 employees so far. “Our differentiation comes from our novel insights and identifying lipid-driven NLRP3 activation as the pathway that we see of highest pathological relevance in neurological, cardiometabolic and in ophthalmic disorders, as well as many of the peripheral disease states,” Estrada said. Multiple biopharmas are in the NLRP3 arena, including Sanofi-backed Ventyx , Novo Nordisk , Ventus , NodThera , BioAge Labs and others. Tenvie follows the blueprint of multiple other drug development startups in recent years that have carved out assets from a public biotech and carried them forward with new investors. The company is operating without a CEO and has no near-term plans for such a post, Estrada said. Its executive chair is ARCH managing director Paul Berns, who previously led the investment firm’s “Really Big Neuroscience Company,” which became Neumora and went public in the fall of 2023. Alongside Estrada in the C-suite are medical chief Tanya Fischer, who recently held the same post at Zenas BioPharma, and business and legal chief Brian Cuneo, a senior partner from ARCH. “Very few times in your career do you get this precious gem in your hands, and I felt like it was too good of a chance to pass up,” Fischer said in an interview. “What I really like is that the molecules have a broad applicability. It’s not narrowed to one disease or disease state.”

Merck is shoring up its neuroscience pipeline with the acquisition of Caraway Therapeutics, a preclinical startup with programs in Parkinson’s disease and amyotrophic lateral sclerosis. Specific financial terms were not disclosed, but Merck said Tuesday that the acquisition agreement could pay out up to $610 million, which includes upfront and milestone payments. Cambridge, Massachusetts-based Caraway develops drugs addressing genetically defined neurodegenerative and rare diseases. The company aims to treat them with small molecules that leverage processes in a cell for clearing away toxic cellular components. Mutations can impair the function of lysosomes, cellular components for breaking down and eliminating toxic substances. Caraway’s small molecules modulate lysosomal function. Caraway has two compounds in its program addressing TRPML1, an ion channel located on lysosomes. One of the molecules is in development for Parkinson’s disease stemming from mutations to the GBA gene, which codes for glucocerebrosidase (GCase), an enzyme key to maintaining lipid metabolism. Deficiency of that enzyme leads to lysosomal dysfunction. By activating TRPML1, Caraway aims to address the pathway that is impaired in GBA-Parkinson’s patients. There’s potential competition in treating genetically driven Parkinson’s. Chicago startup Vanqua Bio is developing small molecules that cross the blood-brain barrier to activate GCase and restore lysosomal function. Gene therapies in development by Neurocrine Biosciences and Eli Lilly offer the potential for a one-time fix of Parkinson’s driven by GBA1 mutations. Another TRPML1-targeting small molecule from Caraway is in development for an undisclosed rare disease that is a non-central nervous system disorder. The company is also researching loss-of-function genetic variants of TMEM175, a potassium channel key to lysosomal function. Caraway is developing small molecules that increase TMEM175’s activity to enhance the activity of the lysosome as a potential treatment for Parkinson’s and ALS. “Caraway’s multidisciplinary approach has yielded important progress in evaluating novel mechanisms of modulation of lysosomal function with potential for the treatment of progressive neurodegenerative diseases,” George Addona, senior vice president, discovery, preclinical development and translational medicine, Merck Research Laboratories, said in a prepared statement. “We look forward to applying our expertise to build upon this work with the goal of developing much needed disease-modifying therapies for these conditions.” Caraway was initially called Rheostat Therapeutics. The startup was incubated by SBV Ventures and the Dementia Discovery Fund, which provided seed financing. In 2018, the startup announced a $23 million Series A round co-led by MRLV, the venture investment group of Merck, and AbbVie Ventures. In 2019, Rheostat changed its name to Caraway Therapeutics. Neuroscience is a tiny portion of Merck’s drug portfolio and pipeline, which is dominated by oncology, mainly the cancer immunotherapy Keytruda. But the company has previously looked at TRPML1 as a way to treat neurodegeneration. In 2019, the pharma giant committed up to $576 million to acquire Calporta Therapeutics, a startup that was developing small molecule agonists of TRPLM1. It’s not clear what became of those programs, which are not listed in the company’s pipeline or financial reports. Merck has also turned to partnerships to bolster its neuroscience prospects. Last year, it paid Cerevance $25 million up front to begin a collaboration discovering new targets for potential Alzheimer’s disease drugs. Image: Dr_Microbe, Getty Images