Alumis (NASDAQ:ALMS) used a virtual key opinion leader event from the American Academy of Dermatology (AAD) Congress to spotlight phase III results for envudeucitinib (also referred to as ESK-001), its next-generation oral TYK2 inhibitor being developed for moderate-to-severe plaque psoriasis. The webcast featured remarks from Chief Financial Officer John Schroer, President and CEO Martin Babler, Chief Medical Officer Dr. Jörn Drappa, and dermatologist Dr. Andrew Blauvelt, who presented the data at AAD as a late-breaker.
Company positioning: “new dawn” for TYK2 inhibition
Babler said clinicians at AAD expressed “strong enthusiasm” for envudeucitinib based on the “totality” of the phase III dataset, highlighting speed of onset, “leading PASI skin clearance,” and patient-reported outcomes. Babler argued the results support the importance of “maximally inhibiting TYK2,” describing TYK2 as an upstream regulator of pathways involving IL-17 and IL-23. He said envudeucitinib was “intentionally designed to deliver 24-hour maximal inhibition of TYK2 with high selectivity,” which the company believes contributes to both efficacy and a favorable safety and tolerability profile.
ONWARD1 and ONWARD2: design and patient population
Dr. Blauvelt said the two phase III trials, ONWARD1 and ONWARD2, used identical designs with three arms: envudeucitinib 40 mg twice daily, placebo, and active comparator apremilast (Otezla) 30 mg twice daily. Patients were randomized 2:1:1. The co-primary endpoints at week 16 were PASI 75 and sPGA 0/1 (clear or almost clear). He noted the company also presented week 24 data because, in his view, responses for IL-23–related mechanisms can continue to improve over the first six months.
On baseline characteristics, Dr. Blauvelt emphasized that about 10% of participants were over age 65 and that disease severity was “pretty severe,” with roughly 70% rated moderate and 30% severe by PGA. He also pointed to baseline itch (pruritus) averaging about 6 out of 10.
Efficacy highlights: PASI 75/90/100 and high-impact sites
At week 16, Dr. Blauvelt reported PASI 75 response rates of 76.5% in ONWARD1 and 70.4% in ONWARD2 for envudeucitinib. PASI 100 (complete skin clearance) was 27.7% and 29.4%, respectively. He described the results as balanced across the two trials and “markedly better than apremilast.”
By week 24, he said PASI 100 increased to 39.5% in one trial and 41% in the other, characterizing ~40% complete clearance at six months as “very impressive.” He added that PASI 90 responses began emerging as early as week 4 and rose to roughly two-thirds of patients by week 24. Dr. Blauvelt also highlighted that PASI 100 rates did not show a plateau through week 24, calling it “exciting” to consider whether responses might continue to rise with longer treatment, while noting the data cannot yet answer that question.
In a subset analysis of moderate-to-severe scalp psoriasis, Dr. Blauvelt said about 75% of patients were clear or almost clear on the scalp at week 24. He emphasized scalp involvement is common—about 80% of psoriasis patients—and can disproportionately affect quality of life.
Patient-reported outcomes: itch and quality of life
Multiple speakers underscored symptom relief and quality-of-life improvements. Dr. Blauvelt said itch scores dropped by roughly 4.3 to 5 points by week 24, starting as early as two weeks after treatment initiation. He also reviewed Dermatology Life Quality Index (DLQI) outcomes, stating that more than 60% of treated patients achieved DLQI 0/1 at week 24, a threshold indicating no effect of disease on quality of life.
Dr. Drappa said the magnitude of itch reduction was “pretty much unprecedented” in his view and noted the U.S. Food and Drug Administration often looks for an average 4-point improvement as a meaningful threshold. He also pointed to a pattern in which improvements in itch and DLQI appeared earlier than high-bar skin clearance (PASI 90), which the presenters argued could be relevant to treatment choice and persistence.
Safety: adverse events, monitoring, and label considerations
On safety through week 16, Dr. Blauvelt said the most frequent adverse event for envudeucitinib was headache (10%), with upper respiratory tract infection and nasopharyngitis also reported. He characterized most adverse events as mild-to-moderate and said they generally did not lead to discontinuation. He contrasted gastrointestinal side effects (nausea and diarrhea) as more typical of apremilast, and said they were not seen to the same degree with envudeucitinib.
Through week 24, he said the overall safety profile was similar, adding there were “no blood test abnormalities,” “no deaths,” “no TB reactivation,” low serious infections, and low malignancies. Dr. Drappa also cited “no concerning signals” related to lab abnormalities, malignancies, serious infections, or cardiovascular events, while noting ongoing long-term follow-up.
In the Q&A, Dr. Drappa addressed questions about tuberculosis testing, stating the company has “an accumulating data set” suggesting TYK2 inhibition does not pose a significant TB reactivation risk and that Alumis had not seen reactivation despite having “about 39 patients or so with a history of latent TB.” Dr. Blauvelt said the theoretical concern stems from IL-12 blockade, but emphasized the trial’s inclusion of latent TB patients without reactivation could support discussions with regulators, while cautioning the final decision rests with the FDA.
On potential monitoring requirements beyond TB testing, Dr. Drappa said that across more than 1,800 patients the company has not observed “evidence of lab abnormalities of clinical importance,” including no trends in lipids, liver function tests, cell counts, or kidney function. Dr. Blauvelt argued label requirements should be “data-driven” rather than “copy and paste” from existing TYK2 labels if the same lab findings are not observed.
Asked about malignancies, Dr. Drappa said exposure-adjusted incidence analyses are ongoing but preliminary data suggest rates are “well within” what is reported in psoriasis populations, and he said the company has not seen imbalances between arms. Dr. Blauvelt added that cancers reported in early months of a trial are unlikely to have developed during that short window and are more appropriately assessed with long-term data.
Next steps: long-term data, additional analyses, lupus readout, and partnering
Management outlined several upcoming milestones. Dr. Drappa said a long-term extension trial is underway, with durability, maintenance, and longer-term safety/tolerability data expected in the second half of the year. He also said additional sub-analyses for palmoplantar disease and nail psoriasis are planned, along with biomarker analyses to explore relationships between biomarkers and clinical outcomes.
Babler said the company anticipates filing an NDA with the FDA and framed the psoriasis results as enabling broader development across immune-mediated diseases, including lupus. He said the company’s ongoing lupus program is a phase IIb study “designed as a pivotal study,” with data expected in the third quarter of this year, which he said could open opportunities in other interferon-driven diseases. Babler also said Alumis plans to announce additional indication plans in the second quarter.
On commercialization strategy, Babler said Alumis continues to view partnering as likely, arguing that developing envudeucitinib (and potentially additional molecules) “on a global level by ourselves across multiple indications is very unlikely.”
Several questions also touched on dosing convenience. Babler said market research suggested a twice-daily regimen could reduce uptake versus once-daily by “about 10%-15%,” but he said twice-daily dosing is “quite far down” on decision drivers; Dr. Blauvelt agreed it is “not a killer,” while still preferring once-daily if achievable. Dr. Blauvelt also said there are plans for pediatric studies after adult development.
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.
