Peloton Therapeutics, Inc.

Pictured: 3D image of a KRAS oncogene iStock/Gilnature BridgeBio announced Thursday that it has secured $200 million in financing to spinout a former subsidiary to develop a KRAS-focused oncology portfolio. Called BridgeBio Oncology Therapeutics (BBOT), the company was initially formed as a subsidiary of BridgeBio known as TheRas. According to an SEC filing, the subsidiary has existed since 2016 and formed a research and development agreement with Leidos Biomedical Research in 2017. BBOT’s mission now is to generate a pipeline of small molecule therapeutics targeting RAS and PI3K malignancies. The company aims to advance three programs, including BBO-8520, a direct inhibitor of KRAS that seeks to bind to the protein’s “on” and “off” states. The spinout is enrolling patients with mutant non-small cell lung cancer in a Phase Ia/Ib trial. A second asset that BBOT will be advancing is BBO-10203, a PI3Kα:RAS breaker that blocks the interaction between RAS and PI3Ka to inhibit the PI3Kα/AKT effector signaling in tumors. The company plans to IND application sometime in the second quarter of 2024 and enroll patients later this year. The other asset is BBO-11818, a pan-KRAS inhibitor that is going after the “on” and “off” states of KRASG12X, and BBOT plans to IND sometime in early 2025. The company is also pursuing a discovery-stage research program focused on developing assets that target additional oncogenic drivers within the RAS and PI3K pathways. “We believe the launch of BBOT better aligns investors with an opportunity that was being hidden in our pipeline, and our partnership with these new investors enables us to prosecute these oncology programs more quickly and with higher fidelity,” BridgeBio CEO Neil Kumar said in a statement. The spinout secured its $200 million financing in an oversubscribed round led by Cormorant Asset Management and co-led by Omega Funds. There was also participation from GV (Google Ventures), Deerfield Management, EcoR1 Capital, Wellington Management, Enavate Sciences, Surveyor Capital, Casdin Captial, Aisling Capital, and Longwood Fund. BBOT will headed by Eli Wallace, BridgeBio’s CEO of oncology R&D. Wallace joined BridgeBio in 2019 after serving as the chief scientific officer at Peloton Therapeutics. Kumar will also serve as a director of BBOT. “In conjunction with BridgeBio and an amazing suite of investors, we look forward to seeing all three of our programs progress into the clinic over the next 12 months,” Wallace said in a statement. BridgeBio has gone down the spinout path before, launching QED Therapeutics in 2018. The company secured $65 million and aimed to develop infigratinib, a cancer asset that Novartis abandoned. Infigratinib was given accelerated approval by the FDA in 2021. Tyler Patchen is a staff writer at BioSpace. You can reach him at tyler.patchen@biospace.com. Follow him on LinkedIn.

Welireg was originally approved by the FDA in 2021 for a rare genetic condition. The latest approval allows the drug to be used in patients with advanced RCC that have previously received checkpoint inhibitors targeting programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) and blockers of vascular endothelial growth factor tyrosine kinase inhibitor (VEGF-TKI). RCC is the most common form of kidney cancer and advanced forms are historically hard to treat ​ with traditional chemotherapy. The arrival of checkpoint inhibitors and VEGF-TKI blockers is providing ever more options for patients with RCC. However, more options are needed for patients whose cancer progresses after receiving these treatments, said a public release from MSD. The approval decision was based on results from phase 3 trial named LITESPARK-005, where belzutifan boosted progression-free survival compared to the renal cell cancer therapy everolimus in patients whose cancer had progressed following treatment with a PD-1 or PD-L1 checkpoint inhibitor and a VEGF receptor targeted therapy. “This approval of Welireg marks the first new therapeutic class available for eligible patients with advanced RCC in nearly a decade,” stated Marjorie Green, senior vice president and head of late-stage oncology, global clinical development, Merck Research Laboratories. Welireg is an oral hypoxia-inducible factor-2 alpha (HIF-2α) inhibitor. MSD first got hold of the compound when it acquired the company Peloton Therapeutics in 2019 for up $2 billion. googletag.cmd.push(function () { googletag.display('text-ad1'); }); The drug was first approved for the treatment of patients with von Hippel-Lindau (VHL) disease who require therapy for certain solid tumors, not requiring immediate surgery. MSD is also developing the drug for the treatment of more types of tumor including biliary tract, colorectal and endometrial cancer.

Merck has blockbuster ambitions for kidney cancer drug Welireg and took a step toward that goal with its second FDA approval for the HIF-2a inhibitor. Since Merck secured approval for kidney cancer pill and blockbuster hopeful Welireg (belzutifan) in August of 2021, sales have grown slowly but surely. With a second FDA nod on Thursday for a much larger patient population, the company can anticipate a more pronounced upswing in revenue from the hypoxia-inducible factor-2 alpha (HIF-2a) inhibitor. The U.S. regulator has given a thumbs up for Welireg to treat relapsed or refractory renal cell carcinoma (RCC) for adult patients who have not responded to a PD-1 or PD-L1 inhibitor and who have also been treated with a vascular endothelial growth factor tyrosine kinase inhibitor (VEGF-TK1). Welireg becomes the first drug in its class for patients with advanced RCC and the first novel-class treatment in the indication since 2015, Merck noted. The nod comes on top of its original approval to treat the rare von Hippel-Lindau disease, a hereditary condition that causes tumor growth in various organs of the body, most often in the kidney. Merck hopes Thursday’s label expansion is the first of a few for Welireg in RCC, as the company is investigating the treatment in earlier lines of use. RCC is the most common form of kidney cancer, accounting for roughly 9 of every 10 cases. In the phase 3 LITESPARK-005 study, Welireg outperformed Novartis’ chemotherapy Afinitor (everolimus), paving the way for the most recent green light. From a pool of 746 patients, after 12 months, 34% of those who received a daily, 120 mg dose of Welireg achieved progression-free survival. That compared with 18% for those on Afinitor. After 18 months, those figures dropped to 22% and 9%, respectively. Welireg also produced a 22% objective response rate, compared with 4% for Afinitor. “Despite recent progress in the treatment of advanced RCC, there is yet to be an option specifically approved for patients whose disease progresses following a PD-1 or PD-L1 inhibitor and a TKI therapy,” Toni Choueiri, the LITESPARK-005 study chair and the director of the Lank Center for Genitourinary Oncology at the Dana-Farber Cancer Institute, said in a release. Merck gained Welireg when it purchased Peloton Therapeutics for $1.05 billion up front in 2019. In the last three quarters, Welireg sales have climbed from $42 million to $50 million to $54 million. When it was approved in 2021, Bernstein analysts pegged Welireg’s peak sales potential between $1 billion and $1.5 billion if it gains approval to treat earlier-stage RCC patients.