Zasocitinib

Pictured: Nasdaq building in New York City/iStock, hapabapa Alumis filed Friday for an initial public offering to raise money for Phase III trials of a potential rival to Bristol Myers Squibb’s Sotyktu (deucravacitinib) and Takeda’s TAK-279. San Francisco-based Alumis is developing two TYK2 inhibitors in conditions such as plaque psoriasis, systemic lupus erythematosus and non-infectious uveitis. BMS won FDA approval for the TYK2 inhibitor Sotyktu in plaque psoriasis in 2022. Takeda acquired a potential challenger to Sotyktu by agreeing to pay Nimbus Therapeutics $4 billion upfront for TAK-279 after seeing Phase IIb data plaque psoriasis in 2022. Alumis’ lead candidate, ESK-001, is trailing Sotyktu and TAK-279 but the biotech contends its molecule is a second-generation TYK2 inhibitor with advantages over the rival products. The biotech, which raised a $259 million Series C round in March 2024, wants public investors to fund work to validate ESK-001. Alumis did not say in its SEC filing how much it aims to raise in the initial public offering (IPO). The company has applied to list its common stock on the Nasdaq Global Market under the ticker symbol ALMS. The biotech is planning to raise enough money to deliver topline Phase III results for ESK-001 in plaque psoriasis, while completing mid-stage studies in systemic lupus erythematosus and non-infectious uveitis. Alumis is also earmarking some cash for a Phase I clinical trial of A-005, another TYK2 inhibitor that is differentiated by its ability to penetrate the central nervous system to treat neurological diseases. Alumis’ pitch for funding rests on the claim that Sotyktu and TAK-279 have been unable to achieve full TYK2 inhibition, limiting their therapeutic potential. The approved Sotyktu dose “provides only partial target coverage,” the biotech said in its IPO filing. Higher doses showed incremental improvements in psoriasis and psoriatic arthritis, according to Alumis, but were associated with skin rashes in up to 9% of patients. BMS saw skin rashes requiring treatment in preclinical tests but no clinically limiting findings were seen in studies of ESK-001. Alumis said skin rashes have been observed at much lower frequency with ESK-001 than rival molecules in humans to date, despite the biotech administering doses that provide “very high and sustained levels of target inhibition.” Alumis plans to start two identical Phase III trials in plaque psoriasis in the second half of 2024 and report topline data from the studies in 2026. The biotech will compare ESK-001 to placebo through Week 16 and Amgen’s Otezla through Week 24. The European Medicines Agency “provided comments on the length” of the studies that Alumis plans to address with comparator trials. Alumis said the “modifications could delay our development timelines for EU regulatory approval and require substantially more resources.” While the biotech is considering running other active comparator trials, it does not expect the data to form part of its U.S. approval filing. Alumis’ IPO filing follows a slowdown in the pace of submissions to list biotechs on U.S. stock markets. A flurry of filings early in the year suggested the IPO window may have reopened after a slow 2023, but the level of activity has fallen since then. Nick Paul Taylor is a freelance pharmaceutical and biotech writer based in London. He can be reached on LinkedIn.

Pictured: 3D illustration of a tumor and its microenvironment/iStock, CIPhoto Nimbus Therapeutics’ small molecule drug candidate NDI-101150 showed strong potential for clinical benefit in patients with advanced solid tumors, the Boston-based biotech announced on Thursday. Results from a Phase I/II study, which will be presented at the American Society of Clinical Oncology annual meeting next week, demonstrated that five out of 30 evaluable patients, or 16.7%, drew clinical benefit from NDI-101150 monotherapy. One patient, who had renal cell carcinoma (RCC), achieved complete response, defined as the disappearance of a tumor and other signs of cancer. Another RCC patient in the dose-expansion cohort showed partial response. Both treatment responders had undergone several prior lines of treatment, including checkpoint inhibitors. Three other patients were able to reach and sustain stable disease for more than six months while undergoing treatment with Nimbus’ drug candidate. These patients had RCC, pancreatic cancer and endometrial cancer, respectively. In terms of safety, the biotech noted that NDI-101150 was “well-tolerated” and that its overall safety profile “remains acceptable.” According to the study’s abstract, 12.8% of treated patients, experienced grade ≥3 treatment-related adverse events. Most common side effects were nausea, vomiting, diarrhea and fatigue. While a 16.7% clinical benefit rate might seem low, Nimbus CMO Nathalie Franchimont in a statement said that the biotech is “encouraged” by these early data which further point to HPK1 “as a differentiated next-generation immunotherapy target” for solid tumors. “NDI-101150 is a potent and highly selective HPK1 inhibitor that has the potential to achieve significant tumor growth inhibition and make a meaningful difference for patients,” Franchimont added. Designed to be orally available, NDI-101150 is a reversible HPK1 inhibitor that works by boosting the activation of T cells, B cells and dendritic cells. The candidate allows the body to “mount a robust anti-tumor response, even under immunosuppressive conditions,” according to Nimbus’ website. NDI-101150 is Nimbus’ only candidate in the clinic and is being developed as a treatment for solid tumors. Aside from its clinical benefit, the Phase I/II study also sought to verify this mechanism of action. Using biopsy samples from an RCC patient on treatment, Nimbus found “increased infiltration” of activated CD8-positive T cells and dendritic cells versus archival biopsies, according to the abstract. A separate portion of the study is testing the combination of NDI-101150 with Merck’s Keytruda (pembrolizumab). Thursday’s readout comes more than a year after Nimbus sold its oral TYK2 inhibitor zasocitinib—along with its wholly owned subsidiary Nimbus Lakshmi—to Takeda for $4 billion upfront, plus potentially $2 billion more contingent on annual sales milestones. Tristan Manalac is an independent science writer based in Metro Manila, Philippines. Reach out to him on LinkedIn or email him at tristan@tristanmanalac.com or tristan.manalac@biospace.com.