Utreloxastat

iStock, JHVEPhoto Monday’s agreement comes days after PTC discontinued the development of another asset, utreloxastat, due to disappointing Phase II data in amyotrophic lateral sclerosis. Novartis and PTC Therapeutics on Monday announced that they have entered into a global license deal to advance the biotech’s Huntington’s disease drug candidate PTC518. As per the terms of the agreement, Novartis will pay $1 billion upfront and will put up to $1.9 billion on the line in developmental, regulatory and sales milestones. PTC will also be entitled to a 40% share of profits in the U.S.—while Novartis will keep 60%—as well as double-digit tiered royalties on sales outside the country. Pending regulatory clearance and other customary closing conditions, the companies expect to complete the transaction in the first quarter of 2025. After unveiling the deal, PTC jumped about 20% before Monday’s opening bell, according to Seeking Alpha . PTC518, the centerpiece of biopharma’s latest multibillion-dollar deal, is a small molecule drug candidate designed to be taken orally. The drug, which can penetrate into the brain, works by lowering the production of the mutant huntingtin protein, with the aim of preventing massive neuronal death and brain injury—both hallmarks of Huntington’s disease (HD) and drivers of its progression. In September 2024, the FDA granted PTC518 its Fast Track designation for Huntington’s. PTC518 is currently being studied in the Phase II PIVOT-HD trial. An interim readout in June 2024 showed a “dose-dependent lowering” of mutant huntingtin protein in the blood and cerebrospinal fluids at 12 months. PTC did not reveal specific data at the time, however noting that there were “favorable trends” in clinical assessments, including Total Motor Score. As per Monday’s agreement, PTC will still be responsible for completing PIVOT-HD—which is likely to occur in the first half of 2025—after which Novartis will take charge of PTC518’s development, manufacturing and completion. Novartis has long been interested in Huntington’s. In March 2022, after discovering that the small molecule drug candidate branaplam could lower levels of mutant huntingtin, the pharma decided to study the drug for Huntington’s instead of its original plan in spinal muscular atrophy. Branaplam is an SMN2 RNA splicing modulator that works by slightly modifying huntingtin mRNA and tagging it for degradation, in turn reducing the overall expression of the huntingtin protein. A few months later, however, the pharma stalled its Huntington’s plans for branaplam after detecting possible side effects. Novartis formally discontinued branaplam for Huntington’s in February 2023. Earlier this year, the pharma again bet on Huntington’s with an up to $1.3 billion deal with Voyager Therapeutics and its pipeline candidates for HD and spinal muscular atrophy. Specifically, Novartis wants to leverage Voyager’s TRACER Capsid Discovery Platform to discover adeno-associated virus capsids to deliver gene therapy payloads into the brain. For PTC, the Novartis agreement comes just days after it axed another asset, utreloxastat, due to disappointing Phase II data in amyotrophic lateral sclerosis.