TMEM175

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

Merck & Co. agreed to acquire Caraway Therapeutics for up to $610 million, bolstering its pipeline with a number of preclinical small-molecule compounds mainly focused on Parkinson’s disease. The deal announced Tuesday includes an undisclosed upfront payment as well as milestones linked to certain experimental drugs.“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,” remarked George Addona, senior vice president for discovery, preclinical development and translational medicine at Merck Research Laboratories.Caraway’s pipeline includes two compounds targeting the TRPML1 ion channel, with one focused on GBA-Parkinson’s disease and the other on an undisclosed non-CNS rare disease. The other two preclinical assets targeting TMEM175 and ATP13A2 are under development for Parkinson’s disease, with the former also being investigated for amyotrophic lateral sclerosis.In 2021, AbbVie paid $17 million upfront for an option on Caraway’s programme targeting the lysosomal potassium ion channel TMEM175. Meanwhile, Merck has been a shareholder of Caraway since 2018 through its MRL Ventures Fund.

This transaction highlights DDF’s attractive strategy of investing in novel therapeutics for dementia, a rapidly escalating public health crisis. BOSTON--(BUSINESS WIRE)-- The Dementia Discovery Fund (DDF), a SV Health Investors (SV) fund specialized in pursuing transformational therapeutic approaches for dementias including Alzheimer's disease, is pleased to announce the acquisition of its portfolio company, Caraway Therapeutics, Inc. by Merck, known as MSD outside the United States and Canada. The companies have entered into a definitive agreement under which Merck will acquire Caraway Therapeutics for a total potential consideration of up to $610 million, including an undisclosed upfront payment as well as contingent milestone payments. Caraway Therapeutics was founded in 2017 by two SV funds, DDF and SV Fund VI, with co-founders including SV Venture Partner, Tim Harris. The firm was created to pursue innovative approaches for the treatment of neurodegenerative and rare diseases by targeting pathways informed by human genetics, and has since built a pipeline of novel, small-molecule therapeutics for the treatment of these diseases. Specifically, Caraway has advanced drug discovery programs against several lysosomal drug targets for Parkinson’s disease, including TRPML1 and TMEM175. “We are excited to have been an investor in Caraway from concept to acquisition, with the end goal of addressing the huge unmet medical need in dementias such as Parkinson’s Disease Dementia and Dementia with Lewy bodies,” says Jonathan Behr, Partner at SV, investing out of DDF, and Director of Caraway at the time of the acquisition. The company was originally incubated and seeded as ‘Rheostat’ by the SV funds. In 2018, the renamed Caraway raised $23 million for its Series A, co-led by MRL Ventures Fund and AbbVie Ventures, with participation from Amgen Ventures, Alexandria Venture Investments and Mayo Clinic, and the SV funds. “The acquisition by Merck is great recognition of the strong science and therapeutic programs the Caraway team has developed, and we are excited by the capabilities and resources that Merck can bring to bear to develop these important medicines,” says Caraway’s former President and CSO, Magdalene Moran. “SV is committed to transforming healthcare through diverse investments,” says Tim Harris, “Through the SV funds’ company creation efforts and focus on providing disease-modifying therapeutics to patients, we are very pleased to advance differentiated science toward treating neurodegenerative diseases and generating returns for our investors.” Under the terms of the agreement, Merck, through a subsidiary, will acquire all outstanding shares of Caraway with earnout milestones associated with the development of certain pipeline candidates. Additional financial details were not disclosed. About the Dementia Discovery Fund The Dementia Discovery Fund (DDF), managed by SV Health Investors, is the world's largest family of specialized venture capital funds that invests exclusively in companies developing or enabling novel therapeutics for dementia. Dementias, including Alzheimer's Disease, are arguably the largest unmet medical need, with over 55m patients worldwide. With more than $500m raised for this strategy, and offices in London and Boston, DDF capitalizes on global investment opportunities to fulfill its mandate of delivering measurable impact and generating significant financial returns. Utilizing its network of venture partners, entrepreneurs, leading scientists, and strategic partners, DDF invests in and creates new biotech companies and provides thought leadership in the field. DDF is enabled by its limited partners including major pharmaceutical companies (Biogen, Bristol Myers Squibb, Eli Lilly and Co., GSK, Johnson & Johnson, Otsuka (Astex), Pfizer and Takeda), along with AARP, Aegon, Bill Gates, British Patient Capital, NFL Players Association, Quest Diagnostics, UnitedHealth Group, and the non-profits Alzheimer's Research UK and LifeArc. Learn more at . About SV Health Investors SV Health Investors is a leading healthcare fund manager committed to investing in tomorrow’s healthcare breakthroughs. The SV family of funds which includes funds dedicated specifically to biotech and dementia, invests across stages, geographic regions, and sectors, with expertise spanning biotechnology, dementia, medical devices, healthcare growth and healthcare technology. With approximately $2.4 billion in assets under management and a truly transatlantic presence with offices in Boston and London, SV has built an extensive network of talented investment professionals and experienced industry veterans. Since its founding in 1993, SV has invested in, created and built more than 200 companies attracting global talent, entrepreneurs and pharma partners. To date, these investments have resulted in the licensing of 24 novel drugs and six new drug classes able to treat indications with unmet medical needs and deliver positive impact to patients. For more information, please see . View source version on businesswire.com: Contacts Source: Dementia Discovery Fund View this news release online at: