Just over a year ago, Nimbus Therapeutics closed one of the biggest single-drug deals in biotech, selling its TYK2 inhibitor to Takeda for $4 billion upfront. Now, CEO Jeb Keiper is planning the company’s next act.
On Thursday, Nimbus shared updated data for NDI-101150, the biotech’s sole clinical-stage drug being tested in cancer patients with advanced solid tumors. In an interview with Endpoints News, Keiper said he’s “incredibly encouraged” by early results from the ongoing Phase 1/2 trial, which showed 5 of 30 patients (17%) with clinical benefit to its small molecule inhibiting the HPK1 protein.
The results are early, but support Nimbus’ belief that it can deliver a successor to immuno-oncology treatments like Merck’s Keytruda. Many of the second-generation I/O drugs targeting proteins like OX40, 4-1BB, and ICOS have disappointed, Keiper said, partly because they were first tested in combination with other drugs without showing clinical benefit on their own. Nimbus’ trial is primarily testing the HPK1 drug alone, with a smaller arm testing in combination with Keytruda.
“The hopes on HPK1 are quite grand,” Keiper said. “Everybody was expecting a lot more from I/O, and now we’re left with King Keytruda, which, gosh, so many cancer patients see, but very little else to answer for afterwards. We do believe it could have the potential to be the next generation as an oral non-checkpoint.”
Nimbus will present its new data at the American Society of Clinical Oncology’s annual meeting, which begins next week. The Boston-headquartered biotech previously presented data on 13 patients last October. The new update, with a data cutoff of March 18, included 44 patients in the dose escalation group and 15 in dose expansion groups.
Nimbus isn’t alone in pursuing HPK1. BeiGene has brought two HPK1 inhibitors — BGB-15025 and BGB-26808 — into the clinic, and will present early data from a Phase 1 dose-escalation study of BGB-15025 at ASCO. An abstract released Thursday stated BGB-15025 as a monotherapy had a 35% disease control rate, but no partial or complete responses. Pfizer, meanwhile, stopped development of its own HPK1 program late last year, citing internal business considerations.
17% showed clinical benefit in all-comers
Among the five patients who have shown clinical benefit on monotherapy, one saw their tumor disappear completely, one saw their cancer significantly shrink, and three had stable disease.
Though 17% showing clinical benefit may seem low, Keiper compared that to similar results from the first studies for Bristol Myers Squibb’s Opdivo. Nimbus’ study is enrolling a wide range of patients with advanced solid tumors who have already tried drugs like checkpoint inhibitors and have seen their cancers continue to grow.
For example, the patient whose tumor got smaller had been previously treated with Opdivo, a combination of Keytruda and Yervoy, and multiple other medicines over about five years before enrolling in Nimbus’ trial. The patient remains on treatment, according to Nimbus’ presentation.
The preliminary data show the drug as generally safe and well-tolerated, with 17% of 59 treated patients reporting a grade 3 or higher treatment-related side effect.
The program is Nimbus’ only drug in human testing after selling its TYK2 inhibitor, zasocitinib, to Takeda. The HPK1 program has spent years in development, with Nimbus first announcing the identification of the compound in May 2020 and dosing the first patient in late 2021.
Keiper acknowledged that Nimbus has more to do in evaluating its drug as a monotherapy. The study is now recruiting patients for expansion cohorts in types of kidney, non-small cell lung, and gastroesophageal cancers.
While HPK1 will play a significant role in Nimbus’ next chapter, it is also advancing a preclinical WRN inhibitor in oncology and expanding its immunology research. Keiper said the biotech, which recently celebrated its 15th birthday, still has no plans to go public or change up its asset-centric approach to drug development. Nimbus raised $210 million in a private financing round last September to fund its next R&D bets.