Calporta Therapeutics, Inc.

Boehringer Ingelheim is investing again in immuno-oncology, announcing Monday a deal to acquire the San Diego-based biotechnology startup Nerio Therapeutics and its slate of preclinical drug candidates.Worth up to $1.3 billion, the acquisition hands Boehringer access to a research program the German pharmaceutical company envisions as a potential key centerpiece of its immuno-oncology drug portfolio. Nerios small molecule drugs are designed to block enzymes known as PTPN1 and PTPN2 that brake the bodys immune response to tumors.Targeting such immune checkpoints has animated much of cancer research and development over the past decade, with mixed results. Checkpoint inhibitors aimed at the proteins PD-1, PD-L1 and CTLA-4 have transformed treatment for many tumors, but drugmakers havent been as successful outside of those targets.In a statement, Boehringer said it believes Nerios small molecules could be potent enough to work as cancer treatment on their own, as well as in combination with other candidates the pharma is currently advancing.Securing the rights to Nerio Therapeutics' novel checkpoint inhibitors creates a broad panel of exciting new cancer treatment combination opportunities, said Paola Casarosa, a member of Boehringers board of managing directors.The company did not disclose how much of the deals value will be paid upfront.On Nerios website, the company says it expects to ask the Food and Drug Administration later this year for clearance to begin clinical testing with its lead asset.The company is backed by Avalon BioVentures and Alexandria Venture Investments, along with a few others. Its co-founders and current executives previously ran Calporta Therapeutics, which Merck & Co. acquired in 2019. '

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

Dive Brief:Merck & Co. will pay as much as $610 million to acquire private biotechnology company Caraway Therapeutics in a deal that expands Mercks research presence in neurodegenerative disease.Announced Tuesday, the deal involves an undisclosed upfront payment along with conditional milestone payments. Merck plans to expense the upfront charge this quarter.Launched five years ago, Caraway specializes in studying the waste disposal machinery of cells. It lists four preclinical drug programs in its pipeline, the most advanced of which target an ion channel thats been on Mercks radar for some time already.Dive Insight:Caraway raised a small Series A round of $23 million in 2018, backed by several pharmaceutical venture arms, including Mercks.At the time, the company went by the name of Rheostat Therapeutics. It rebranded to Caraway one year later, but kept its focus on developing treatments for rare and neurological diseases that work by restoring cellular balance.While the company has kept a low profile since, Merck appears to have liked what its seen from the companys emerging pipeline.Its two advanced programs target the ion channel known as TRPML1, which can regulate how the lysosome removes cellular waste. Caraway is exploring how targeting the protein could help treat Parkinsons disease linked to mutations in a gene called GBA, as well as non-central nervous system rare diseases.Merck previously bet on TRPML1-targeting drugs. In 2019, the drugmaker acquired a small biotech called Calporta Therapeutics in a deal worth $576 million. Calportas pipeline consisted of drugs that supported lysosome activity by targeting the TRPML1 ion channel.Pharma investment in neuroscience has shown signs of rebounding in recent years, after many large drugmakers exited or deprioritized the field at the end of the last decade following clinical setbacks.For Merck, the planned acquisition is the latest in a busy year of dealmaking. Earlier in 2023, the company acquired Prometheus Therapeutics about $11 billion, gaining a late-stage bowel disease drug. And in October, Merck agreed to pay $5.5 billion to Daiichi Sankyo to gain access to three antibody-drug conjugate cancer drugs. '