Xanomeline Tartrate/Trospium Chloride

Steve Paul is back with a fresh take on schizophrenia drugs, co-founding a new biotech called Syremis Therapeutics that’s already landed $165 million in a Series A, Endpoints News has learned. The serial founder and force behind the $14 billion sale of Karuna Therapeutics is making his next bet on the M1/M4 muscarinic agonist approach that helped spark a resurgence in psychiatric drug development and pharma dealmaking. The Series A funding came together earlier this month, Syremis told Endpoints. For Paul, one goal is to beat Cobenfy, which he helped shepherd through clinical development in a rotation of executive positions over the years. While Cobenfy (formerly known as KarXT) is already being prescribed to patients — and companies such as MapLight Therapeutics are also making inroads — the target at Syremis is less about speed and more about pursuing a best-in-class approach. “It’s often not the first-in-class that become the most important medicines in a given space, if you look at statins or almost any drugs, SSRIs, SNRIs,” Paul, who was Karuna’s chair and CEO at one point, said in an interview. It’s the second or third drug that “becomes the most important medically and commercially.” The $165 million will get Syremis’ investigational M1/M4 muscarinic agonist and NMDA antagonist through Phase 2 proof-of-concept studies, set to begin around 2027, co-founder and CEO Elisabeth Kogan said in a joint interview with Paul. The Series A was led by Third Rock Ventures and Dexcel Pharma, which is known for being the founding investor in Roivant Sciences. Other backers include Bain Capital Life Sciences, Google Ventures, QVT and Pictet. Syremis’ origins trace to Israeli startup Clexio Biosciences, which has brought multiple experimental neuro medicines into the clinic since its 2018 founding. Clexio spun out Syremis in this year’s second quarter with many of its team members moving to the new entity, which now has about 30 employees. Other Syremis co-founders include chief development officer Elena Kagan and technology chief Menashe Levy. Kogan declined to comment on the future of the Clexio pipeline programs that didn’t make the move. Paul said his Karuna team never came across Clexio and its M1/M4 program while developing Cobenfy, describing the Israeli company as having been mainly in stealth mode. Kogan reached out to him after Bristol Myers Squibb bought Karuna. Now, Syremis’ ST-905 is in a healthy volunteer study in Europe, with plans to expand that Phase 1 into the US next year, Kogan said. The M1/M4 muscarinic agonist is being tested as a once-daily oral drug, versus Cobenfy’s twice-daily profile. Paul and Kogan said they haven’t seen any liver toxicities with ST-905. Paul said ST-905 has “much higher oral bioavailability, so less variability patient to patient” than Cobenfy. Eventually, Syremis plans to test a once-monthly injectable version as well, in hopes of helping with compliance of the drug, the CEO said. Adding an injectable would also likely extend the drug’s life on the market. Lyndra Therapeutics, another biotech working on a long-acting version of a different type of schizophrenia drug, shut down earlier this year. Syremis will look to repeat Karuna and Bristol Myers’ strategy of bringing ST-905 into other indications, such as Alzheimer’s disease psychosis and agitation, Kogan said. Beyond schizophrenia, Syremis is also in the major depression space with an NMDA antagonist called ST-901 that will enter Phase 1 around the middle of next year, Kogan said. Johnson & Johnson broke open this field with its blockbuster nasal spray, the esketamine product known as Spravato. Axsome Therapeutics has an oral NMDA-directed drug called Auvelity; Syremis is working on an oral medicine as well. The biotech’s board includes Paul, Kogan, Dexcel co-CEOs Ilan Oren and Uri Oren, Third Rock’s Reid Huber, and Bain Capital’s Ray Sanchez. Sanchez was previously chief medical officer of Cerevel. Shortly after AbbVie bought Cerevel, its schizophrenia drug failed a key clinical trial, dooming AbbVie’s hopes of quickly following Cobenfy.