Repare Therapeutics, Inc.

Today, a brief rundown of news from Novo Nordisk and Ventyx Biosciences, as well as updates from Novartis and Pfizer that you may have missed.A pooled analysis of data from four trials of Novo Nordisks obesity drug semaglutide found treatment reduced the risk of cardiovascular death or worsening heart failure by 31% compared to placebo. The results, which were published in The Lancet on Friday, could help Novo expand use of the drug into heart failure. The company had previously applied to the Food and Drug Administration for such an approval, but recently withdrew it in order to submit additional relevant data. The Lancet analysis, which focused on 3,700 participants across the four trials who had heart failure with preserved ejection fraction, was post-hoc. Ned PagliaruloMartin Auster, chief financial officer of Ventyx Biosciences, has departed the inflammatory disease drug developer, the company announced Friday. He will be replaced on an interim basis by Roy Gonzales, who will serve as interim principal financial officer for SEC reporting purposes. Ventyx, which has hit setbacks in developing a so-called TYK2 inhibitor, said it will search for a permanent replacement. Ned PagliaruloEmergent BioSolutions on Thursday said the Food and Drug Administration granted extended an approval of its smallpox vaccine so it can also be used to prevent mpox in people at high risk for infection. The single-dose vaccine, called ACAM2000, was initially cleared for smallpox back in 2007. Thursdays approval was based on a previous human trial and animal testing, which showed the vaccine to be effective in protecting against mpox, according to Emergent. Mpox was declared a public health emergency by the World Health Organization on Aug. 14 after outbreaks in parts of Africa. Jynneos, from Bavarian Nordic,is the only other available vaccine for mpox in the U.S. Delilah AlvaradoCancer drugmaker Repare Therapeutics plans to lay off 25% of its workforce as part of a strategic reprioritization disclosed Wednesday. The company will focus on its more advanced, clinical-stage programs and scale back preclinical research. The layoffs are expected to mainly affect staff in its preclinical group. The company said the reorganization will generate annual savings of approximately $15 million, pushing out its cash runway into the second half of 2026. Delilah AlvaradoFlagship Pioneerings ongoing research alliance with Pfizer has yielded more leads for the pharmaceutical giant, the companies said Wednesday. The company creation firm will work with its portfolio company Quotient Therapeutics on two research programs to support development of drugs for heart and kidney diseases. In June, Flagship announced it would tap ProFound Therapeutics to look for promising obesity drugs Pfizer can choose to advance. Gwendolyn Wu '

“We acknowledge the extraordinary contributions and productivity of our discovery team,” Repare Therapeutics CEO Lloyd Segal said in the company's release. Repare Therapeutics is laying off a quarter of its workforce as the oncology biotech scales back its preclinical work to focus on more advanced candidates such as a synthetic lethal drug handed back by Roche earlier this year.The biotech had a number of synthetic lethal targets in advanced stages of preclinical development, according to the company’s website. But Repare has decided to “materially reduce the scale of its preclinical research and discovery activities,” the company said in a post-market release Aug. 28.This “strategic refocus” will see the company reduce its overall workforce by around 25%, with the biotech’s preclinical group bearing the brunt of the layoffs. Repare had 179 full-time employees as of February, of which 143 were primarily engaged in some form of R&D and 36 were focused on management or general and administrative activities. The redundancies outlined yesterday are expected to incur between $1.5 million and $2 million of costs in the third quarter before generating annual savings of $15 million.Repare ended June with $208.1 million in cash and equivalents, which it had estimated would fund its operations until at least mid-2026. The savings outlined in the Aug. 28 release are expected to pave a cash runway further into that year.“We acknowledge today the extraordinary contributions and productivity of our discovery team, who have enabled the development of our deep, innovative clinical portfolio,” Repare’s CEO Lloyd Segal said in the release.“In our mission to rapidly develop new, practice-changing therapies, we will more fully dedicate our resources to our most promising and advanced precision oncology programs to maximize value for patients and for our shareholders,” Segal added.Those programs include a phase 1 dose expansion trial of a combination of the biotech’s lunresertib and camonsertib in patients with ovarian and endometrial cancers due to read out in the fourth quarter of 2024. Segal has previously touted phase 1 data of the PKMYT1 inhibitor lunresertib as “really phenomenal,” while the ATR inhibitor camonsertib made headlines in February when Roche walked away from a collaboration on the drug just days after the Big Pharma had dosed the first patient in a phase 2 trial. Undeterred by the rejection, Repare has hopes to launch a registrational trial of the lunresertib-camonsertib combo next year. The biotech is also assessing camonsertib as a monotherapy in a phase 2 trial in non-small cell lung cancer, which is due to read out next year.The company’s phase 1 pipeline also consists of a PLK4 inhibitor called RP-1664 that is in a study for patients with TRIM37-high solid tumors along with a Polθ ATPase inhibitor called RP-3467 that is set to enter human trials in the fourth quarter.

Repare Therapeutics is cutting its headcount by about 25%, with most of the layoffs concentrated in the company’s preclinical team, as part of what the company is calling a “strategic prioritization” of its R&D program. The move will allow Repare to focus on clinical-stage oncology candidates. That includes lunresertib and camonsertib, which are currently being evaluated together in a Phase 1 trial for patients with ovarian and endometrial cancers. The trial is now in the dose expansion phase, data are expected in the fourth quarter, and a registrational trial could begin as early as 2025. Camonsertib is also being investigated as a monotherapy in non-small cell lung cancer as part of a Phase 2 trial, with data expected in 2025. Roche had licensed camonsertib, an oral ATR inhibitor, back in 2022 but bowed out in February, shortly after paying $40 million for dosing the first patient with the drug in a different Phase 2 platform study. The deal originally carried up to $1.2 billion in milestones. The company also has RP-1664, an oral inhibitor of PLK4, in a Phase 1 trial in adult and adolescent patients with TRIM37-high solid tumors. Based on safety data, Repare said it will move the therapy into a Phase 1/2 study in pediatric patients with high risk, recurrent neuroblastoma, where prevalence of TRIM37-altered tumors is high. “In our mission to rapidly develop new, practice-changing therapies, we will more fully dedicate our resources to our most promising and advanced precision oncology programs to maximize value for patients and for our shareholders,” Repare president and CEO Lloyd Segal wrote in a statement. The staff reduction will cost the company non-recurring cash payments of about $1.5 million to $2 million in the third quarter of this year — but it expects annual savings of around $15 million that will extend its cash runway into the second half of 2026. Stifel analysts wrote in a Wednesday note that “the reprioritization has a small positive impact,” and that “focusing resources on clinical efforts with near-term inflection points makes sense.”