Executives from Alumis (NASDAQ:ALMS) outlined upcoming regulatory milestones and provided additional context around recently announced Phase 3 psoriasis results for envudeucitinib during a fireside chat at Oppenheimer’s Annual Healthcare Conference.
Phase 3 psoriasis update: primary endpoint and response depth
CEO Martin Babler said the company has been “very cautious” and “disciplined” in what it has publicly disclosed so far because it intends to submit the dataset as a late-breaking abstract to the American Academy of Dermatology (AAD) meeting.
The company also disclosed week 24 outcomes for more stringent endpoints, including an average PASI 90 rate of about 65% and an average PASI 100 rate “just about over 40%.” Babler said placebo rates for PASI 90 and PASI 100 were in line with historical experience.
He added that envudeucitinib showed rapid onset, with separation versus placebo emerging by week 4 for PASI 75 and PASI 90, and a “deepening response” over time between weeks 16 and 24. Babler also cited clinically meaningful improvements in quality of life, itch, and other patient-reported outcomes.
Safety observations and labeling questions
On safety, Babler said the Phase 3 profile was consistent with Phase 2 experience, highlighting headaches, upper respiratory tract infection, nasopharyngitis, and acne as the “four largest manifestations” of safety and tolerability observed in the trials. He said the company did not see a malignancy signal and did not observe blood chemistry changes that would suggest laboratory monitoring would be needed.
In response to questions about the monitoring requirements on Bristol Myers Squibb’s deucravacitinib label, Babler said Alumis has “not really seen any change in triglycerides or liver enzymes” and argued that such findings are more likely molecule-specific than target-related. He also stated the company has “really not seen any JAK pharmacology,” emphasizing that TYK2 affects different cytokines than some JAK targets.
Addressing malignancy concerns, Babler said there is always a background cancer rate in trials of this size and reiterated that Alumis does not believe it has a malignancy signal. He referenced two malignancy cases previously observed in the Phase 2 open-label extension and described them as unlikely to be drug-related: one renal cancer that appeared to predate treatment due to its size and slow growth, and one lung cancer case associated with an EGFR mutation and family history. He said the company expects to disclose more detailed safety data at a future medical meeting, “hopefully at AAD.”
Dosing and formulation strategy: BID now, QD later
Envudeucitinib’s Phase 3 program used a twice-daily (BID) formulation, and Babler said the company has developed a once-daily (QD) formulation with the pharmacokinetic/pharmacodynamic profile it sought, including attention to trough levels (Cmin) alongside conventional metrics like Cmax and AUC. However, he said there were other formulation features the company “didn’t like,” prompting additional work.
As a result, Babler said the QD formulation will not be the launch formulation and is now positioned as a lifecycle extension. He added that the timeline will become clearer once the company identifies the engineering solution it wants to pursue.
Babler also discussed market research indicating that when patients were asked to choose between a BID drug with no food effect and a QD drug requiring fasting, roughly two-thirds preferred the BID option in that scenario. He said research suggests BID versus QD with no food effect may result in a slight loss in market share, but emphasized that the overall oral psoriasis market could expand substantially as more agents enter the category.
Regulatory plans and commercialization: NDA in 2H, partnering likely
On next steps, Babler said Alumis plans to submit an NDA in the second half of the year. He attributed the timing to the structure of the Phase 3 program, noting the company already has 24-week data and expects to receive 48-week data by mid-year. He added that part of the 48-week dataset includes a randomized withdrawal component intended to support label claims around durability and maintenance, which he said drives the planned second-half filing.
Commercially, Babler said the company has a “small but mighty” team and plans to decide by year-end whether to ramp up commercialization internally or externally. He framed the decision as broader than psoriasis, tied to what Alumis wants to do with its broader TYK2 franchise and the practical limits of launching and developing the drug across up to 20 identified indications on a global basis. In that context, he said the company believes partnering is the most likely outcome, with the remaining question being what the partnership structure and Alumis’ role would be.
Lupus readout in Q3 and pipeline considerations
Babler also highlighted systemic lupus erythematosus (SLE) as a major upcoming catalyst. He said Alumis’ ongoing Phase 2b lupus study is designed as a pivotal trial, with alignment from regulators on what it would need to include. The trial enrolled more than 400 patients, tests three active doses versus placebo, and has a 48-week endpoint. Enrollment completed last summer, and Babler said the company expects to report results in the third quarter. The primary endpoint is BICLA, with SRI-4 as the first secondary endpoint.
He said the company sees validation for TYK2 in lupus based on genomics, the success of anifrolumab (an interferon inhibitor) in SLE, and prior positive Phase 2 data for deucravacitinib in lupus. Babler said key execution factors include patient selection, consistent use of lupus assessment tools, and careful management of concomitant medications—particularly steroids—citing a forced taper to 5 mg or less within a specified timeframe.
On regulatory pathways for lupus, Babler said Alumis’ base-case assumption remains that it may need one additional Phase 3 trial, while an upside case could involve discussing conditional approval with a confirmatory Phase 3 run in parallel, depending on the strength of the dataset. He said the pivotal question may center on safety requirements and whether safety data from psoriasis and other trials can support the lupus package.
Beyond envudeucitinib, Babler said the company is evaluating its TYK2 portfolio as a “franchise,” including how to position a CNS-penetrant TYK2 candidate and whether to consider peripheral indications as well, with more updates expected in the “not-too-distant future.” He also discussed ongoing work on lonigutamab, saying Alumis believes it is a differentiated asset and is exploring mechanistic questions, including hypotheses related to IGF-1 and potential inner ear effects. Babler said the company expects to decide how best to move forward with lonigutamab in the first half of this year.
About Alumis (NASDAQ:ALMS)
Our mission is to significantly improve the lives of patients by replacing broad immunosuppression with targeted therapies. Our name, Alumis, captures our mission to enlighten immunology, and is inspired by the words “allumer”-French for illuminate-and “immunis”-Latin for the immune system. We are a clinical stage biopharmaceutical company with an initial focus on developing our two Tyrosine Kinase 2 (TYK2) inhibitors: ESK-001, a second-generation inhibitor that we are developing to maximize target inhibition and optimize tolerability, and A-005, a central nervous system (CNS) penetrant molecule.
