Clexio Biosciences Ltd.

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.

Syremis Therapeutics made its debut Thursday with $165 million in series A financing in hand, hoping to carve out a foothold in a space reshaped by the FDA approval last year of Bristol Myers Squibb's dual M1/M4 muscarinic agonist Cobenfy (xanomeline / trospium chloride) for schizophrenia.Co-led by Dexcel Pharma and Third Rock Ventures, the round also drew participation from the likes of Bain Capital Life Sciences, GV, QVT and Pictet.The startup's lead asset, ST-905 – which, like Cobenfy, also targets the M1 and M4 muscarinic receptors – is working its way through Phase I, targeting schizophrenia as well as other neuropsychiatric disorders."Schizophrenia and Alzheimer's disease psychosis remain two of the most challenging of all neuropsychiatric disorders," said Steve Paul, Syremis co-founder and former CEO of Karuna Therapeutics, the company BMS shelled out $14 billion for in 2023 to get its hands on Cobenfy, then still in development and known as KarXT.'Balanced' M1/M4 profilePaul, who now sits on the Syremis board, suggested ST-905's "balanced M1/M4 profile and promising pharmaceutical properties" could allow the company to build on the clinical progress made by Cobenfy (see – JPM25: BMS looks to position Cobenfy as a 'pipeline within a product'). Though it hasn't all been smooth sailing for BMS's drug; earlier this year it failed to showed enough benefit in a Phase III trial as an add-on therapy for schizophrenia, and more recently, a review tuned up clinical site "irregularities" in another study, this time for or psychosis associated with Alzheimer's disease.The muscarinic target has also seen disappointing results elsewhere, with AbbVie's emraclidine – a selective M4 muscarinic modulator – failing to live up to expectations in a pair of mid-stage schizophrenia studies late last year.Syremis argues that ST-905's "differentiated" potency and properties could make it a best-in-class therapy across multiple neuropsychiatric indications and symptom domains, while also supporting once-daily oral dosing and the potential for a long-acting injectable version.Meanwhile, the startup's second programme, ST-901, takes a different tack. That asset is an NMDA receptor antagonist currently in IND-enabling studies, with plans to enter Phase I next year for major depressive disorder and bipolar depression.Both ST-905 and ST-901 originated at Clexio Biosciences before being spun out into Syremis, which is led by CEO Elisabeth Kogan.

TEL AVIV and PETAH TIKVA, Israel, Feb. 6, 2023 /PRNewswire/ -- As part of a shared commitment to bring better solutions for people suffering from depression, Clexio and Genetika+ are partnering to screen and characterize Clexio's antidepressant pipeline using Genetika+'s iPSC-derived neurons platform. Genetika+'s platform encompasses >200 neuronal lines from depression patients with in-depth clinical and demographic characterization and multiple assessments over the course of 12 months, as well as proprietary multi-modal biomarker read-outs on these neurons. The Genetika+ platform allows, for the first time, assessment of the functional effects of drugs directly on human neurons, the key target cells of antidepressants, with biologically-relevant biomarkers that have been demonstrated to correlate with clinical response. This assessment not only enables a readout of the antidepressant effect of a candidate drug, but also allows for the characterization of a compound with respect to its effect on different depression subpopulations, including those with varying response patterns to other drugs. Clexio's CEO and co-founder, Elisabeth Kogan, said: "we are looking forward to working with Genetika+ and leveraging their unique platform for valuable insights as we develop new therapeutics for Major Depressive Disorder, and to contributing to the advancement of personalized medicine for psychiatry". "The ability to obtain functional readouts, which have been studied for decades with a wealth of scientific support behind them, directly from patients suffering from CNS-related diseases, is transformative for the way we diagnose and manage these diseases. This has the potential to transform mental health and neurological diseases in the same way that the molecular characterization of tumors has transformed oncology" said Talia Cohen Solal, co-founder and CEO of Genetika+. Clexio Biosciences is a CNS-first clinical stage pharmaceutical company with a broad and growing pipeline. Clexio is dedicated to developing novel therapies for patients suffering from neurological and psychiatric conditions. One of our driving principles is to invent new therapeutic modalities and bring them quickly from an idea to Proof of Concept and then to full clinical development. Our experienced team of leaders in neuroscience identify points of convergence between unmet medical needs, validated mechanisms of action and technology, to generate new patient-centric possibilities. To learn more about us and our pipeline: Genetika+, founded in 2018 by Talia Cohen Solal, Ph.D., and Daphna Laifenfeld, Ph.D., is developing personalized medicine solutions to optimize treatment for psychiatric and neurological diseases. The company's Brain-in-a-Dish technology helps physicians find the best treatment for their patients. In its first indication, depression, Genetika+ uses patented technology to rapidly test more than 70 approved antidepressants and drug combinations against an individual patient's unique neurological biomarkers. Combined with patients' genetic and medical history, Genetika+ can predict the optimal drug or combination therapy for each patient. This opens the door to faster treatment, fewer side effects, and lower dosing, and the elimination of arduous trial-and-error treatment protocols and needless loss of life. To learn more, follow us on LinkedIn or on Twitter @Genetikaplus. Contact: Michael Falcone MacDougall Advisors Mfalcone@macdougall.bio +1781-591-3448 Logo - Logo -