Shares of Prometheus Biosciences Inc. (NASDAQ:RXDX) were trading midday at $192.97, up $78.96, or 69% as Wall Street learned of the $10.8 billion buyout by Merck & Co. Inc., which has agreed to pay $200 cash per share. The deal brings aboard phase II-stage PRA-023, a humanized monoclonal antibody directed to tumor necrosis factor-like ligand 1A, known to be associated with intestinal inflammation as well as fibrosis. Last December, Prometheus rolled out data with the compound in ulcerative colitis and Crohn’s disease.

AACR 2023: Cancer vaccine trial results elicit reactions from “indisputable” to “cautious optimism”

Combining the personalized cancer vaccine mRNA-4157 (V940, Moderna Inc.) with Keytruda (pembrolizumab, Merck & Co. Inc.) significantly extended recurrence-free survival in patients with stage III/IV resected high-risk melanoma in the randomized phase II KEYNOTE-942/mRNA-4157-P201 trial. Compared to Keytruda alone, adding the vaccine cut the risk of recurrence or death by 44% 18 months after treatment, lead investigator Jeffrey Weber reported at the opening clinical trials plenary of the 2023 annual meeting of the American Association for Cancer Research (AACR). There was broad agreement that those data were good enough to start a phase III trial as well as a broader development program, with non-small-cell lung cancer and squamous cell carcinoma of the head and neck being top contenders for additional studies.

Pipeline strikes $1B deal with Janssen for myelin restoration candidate in MS

Pipeline Therapeutics Inc., which received U.S. FDA approval to move into a phase Ib/IIa study of PIPE-307 in relapsing-remitting multiple sclerosis (RRMS) last year, will be advancing the oral, small-molecule muscarinic M1 receptor antagonist in collaboration with Janssen Pharmaceutica NV in an agreement that could be worth more than $1 billion. Under the terms, Pipeline will grant Janssen, a unit of Johnson & Johnson, worldwide rights to PIPE-307 in all indications, though Pipeline will have the right to continue moving the product in RRMS through phase II. Pipeline will get $50 million up front, up to $25 million from Johnson & Johnson Innovation – JJDC Inc., and up to $25 million in equity investments from Pipeline’s existing investors. Beyond that, Pipeline is eligible for up to $1 billion in milestones, plus double-digit royalties.

FDA adcom debates efficacy of Entasis’ infection drug

Entasis Therapeutics Inc. spent the morning making its case to the U.S. FDA’s Antimicrobial Drugs Advisory Committee for approval of injectable sulbactam-durlobactam (Sul-Dur) to treat one of the toughest hospital-acquired infections. Sul-Dur, a combination beta-lactam antibiotic and beta-lactamase inhibitor for treating carbapenem-resistant Acinetobacter baumannii infections, has a May 29 PDUFA date. After hearing from Entasis and FDA analysts, the advisory committee will vote yes or no if it thinks the overall benefit‐risk assessment is favorable for using Sul-Dur to treat adults with hospital‐acquired bacterial pneumonia and ventilator‐associated bacterial pneumonia caused by susceptible strains of Acinetobacter baumannii‐calcoaceticus complex organisms. The FDA is not obligated to follow the committee’s guidance but often does.

Intelgenx gains US approval for migraine drug Rizafilm

After issuing three prior complete response letters, the U.S. FDA finally granted approval via the 505(b)(2) NDA pathway to Intelgenx Corp.’s Rizafilm Versafilm to treat acute migraine. The drug, an oral thin film formulation of rizatriptan benzoate, the active ingredient in Merck & Co. Inc.’s Maxalt, is targeting a global market expected to reach $10 billion by 2030, according to Clarivate’s Disease Landscape & Forecast data. Rizafilm is the U.S. tradename for what is known as Rizaport in Europe, where it first gained German approval in 2015. 

Complement Therapeutics closes $79M A round for gene therapy in geographic atrophy

Complement Therapeutics GmbH raised €72 million (US$79.4 million) in a series A round to move into the clinic a novel gene therapy for treating geographic atrophy secondary to dry age-related macular degeneration (AMD). It’s the largest series A round completed in Europe so far this year. The company is now legally headquartered in Munich, a function of its European investor syndicate, but it is a creation of the U.K. innovation ecosystem. Complement Therapeutics (CTx) was spun out of the University of Manchester to take forward research on the complement system conducted by its founders Simon Clark, Paul Bishop, and Richard Unwin. 

AACR 2023: Thinking of heterogeneities as multiple shots on goal

Heterogeneity, in both tumors and their microenvironment, limits the success of current cancer treatments. But it also provides opportunities. Heterogeneities “are not barriers to therapy, they are vulnerabilities to be exploited,” was how David DeNardo described his take at the 2023 annual meeting of the American Association for Cancer Research (AACR) on Sunday. DeNardo is a professor of medicine and of pathology & immunology at Washington University in St. Louis. He and his team study the role of macrophages and dendritic cells in antitumor immunity. In his talk on “Learning immunology from immunotherapy success and failure” at the AACR opening plenary, he gave examples of how heterogenous vulnerabilities might be exploited in practice.

Newco news: Adaptyv Bio using cell-free systems to generate high-affinity proteins

The artificial intelligence-first approach to drug discovery may be boosting productivity but has also exposed the fact that in silico design can only go so far. At some point it will be necessary to revert to the conventional method and synthesize a protein and do an experiment. Now newco Adaptyv Bio aims to smooth this transition by applying cell-free systems and micro fluidics to enable proteins to be synthesized and validated at nano scale. That means 1,000 times fewer reagents are consumed, and thousands of different proteins per day can be screened in any experiment.  

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