8-K: Alumis posts strong Phase 3 psoriasis results

Envudeucitinib met all primary and secondary endpoints in two Phase 3 ONWARD trials with high Week 24 skin-clearance rates and a favorable safety profile; NDA planned for H2 2026.

Summary

• Envudeucitinib (40 mg twice daily) achieved robust efficacy in two 24-week, randomized, double-blind, placebo- and apremilast-controlled Phase 3 trials (ONWARD1 and ONWARD2) in moderate-to-severe plaque psoriasis (>1,700 patients enrolled 2:1:1).
• Week 16 outcomes: PASI 90 of 59.9% (ONWARD1) and 53.1% (ONWARD2) vs placebo 4.8% and 4.3%; PASI 100 of 29.4% and 27.7% vs placebo 0.9% and 0.9%; PASI 75 of 76.5% and 70.4% vs placebo 18.7% and 13.7% (all p<0.0001 vs placebo and apremilast).
• Week 24 outcomes: PASI 90 of 68.0% (ONWARD1) and 62.1% (ONWARD2); PASI 100 of 41.0% and 39.5%; PASI 75 of 78.6% and 75.1%, showing continued improvement from Week 16.
• Rapid onset: separation from placebo by Week 4 for PASI 90; approximately three in four patients with baseline scalp involvement (ss-PGA 3) achieved ss-PGA 0/1 by Week 24, with >30% responding by Week 4.
• Patient-reported outcomes: mean worst pruritus NRS improvement >4 points by Week 16 (with meaningful relief as early as Week 2); ~50% of eligible patients achieved DLQI 0/1 by Week 12, with continued improvement through Week 24.
• Safety through Week 24: generally well tolerated, no deaths, no MACE or cytopenia signals, no TB reactivation; low SAEs (2.7% by Week 24) and discontinuations (2.7%); most frequent TEAEs included headache, nasopharyngitis, URTI, and acne; serious infections 0.7% and malignancies 0.2% in envudeucitinib-treated patients at Week 24.
• Alumis plans to submit a U.S. NDA in H2 2026; one-year Phase 3 long-term data expected H2 2026; once-daily formulation and a pediatric plan are under development.
• The ONWARD3 long-term extension is ongoing; LUMUS Phase 2b in systemic lupus erythematosus (SLE) has topline data expected in Q3 2026.
• Results were presented at a late-breaking oral session at the 2026 AAD Annual Meeting (Mar 28, 2026); an investor webcast was scheduled for Mar 29, 2026 at 5:00 pm MDT / 7:00 pm EDT.

Sentiment

Score: 8

Explanation: StockSavvy.ai views this as a materially positive clinical update: robust efficacy that improves through Week 24 with a clean safety profile de-risks the NDA path, though regulatory and long-term safety uncertainties remain.

Positives

• All primary (PASI 75 and sPGA 0/1 at Week 16 vs placebo) and secondary efficacy endpoints met across both ONWARD trials.
• High skin-clearance rates that deepened from Week 16 to Week 24: PASI 90 reached 68.0% (ONWARD1) and 62.1% (ONWARD2); PASI 100 reached 41.0% and 39.5%.
• Rapid onset with significant separation from placebo by Week 4 and early improvements in itch and quality of life preceding PASI 90 responses.
• Strong scalp psoriasis results: about 75% achieved ss-PGA 0/1 at Week 24 (baseline ss-PGA 3), with >30% response by Week 4.
• Favorable safety and tolerability consistent with Phase 2, with low rates of SAEs (2.7% through Week 24) and discontinuations (2.7%); no MACE, no TB reactivation, and no clinically significant lab abnormalities reported.
• Clear superiority to apremilast on key endpoints at Week 16 (e.g., PASI 90 ~60%/53% vs ~21%/21% in ONWARD1/2; p<0.0001).
• Large, global, well-controlled Phase 3 dataset (>1,700 patients) enhances robustness and generalizability.
• Regulatory trajectory defined with NDA planned in H2 2026 and additional catalysts (one-year LTE data in H2 2026; SLE Phase 2b readout in Q3 2026).

Negatives

• Dosing is currently twice daily (40 mg BID); once-daily formulation is still under development.
• Long-term efficacy and safety beyond 24 weeks remain to be confirmed; one-year Phase 3 data are pending in H2 2026.
• No head-to-head data vs other TYK2 inhibitors or leading biologics; cross-trial comparisons are indirect.
• Treatment-emergent adverse events included headache, nasopharyngitis, upper respiratory tract infection, and acne (mostly mild).
• Regulatory risk remains: approval is not assured despite positive efficacy and safety data.
• Low but non-zero rates of serious infections (0.7%) and malignancies (0.2%) observed at Week 24 in envudeucitinib-treated patients.

Risks

• Regulatory authorities may determine envudeucitinib is not sufficiently safe and efficacious in moderate-to-severe plaque psoriasis and may not grant approval.
• Regulatory authorities may not accept for filing the planned NDA submission.
• Ability to obtain regulatory approvals and ultimately commercialize clinical candidates is uncertain.
• Timing and results of ongoing and future preclinical and clinical trials could differ from expectations.
• Ability to fund development activities and achieve development goals may be constrained.
• Ability to protect intellectual property may impact future prospects.

Future Outlook

Alumis plans to submit an NDA for envudeucitinib in H2 2026, expects one-year Phase 3 data in H2 2026, is developing a once-daily formulation and a pediatric plan, continues the ONWARD3 long-term extension, and anticipates topline data from the LUMUS Phase 2b SLE program in Q3 2026.

Management Comments

• “Envudeucitinib delivered the level of skin clearance, symptom relief, and safety in Phase 3 that the TYK2 mechanism has long promised but that has not been fully realized—until now—with sustained, maximal 24-hour inhibition of the IL-23 / IL-17 pathways,” said Dr. Jörn Drappa, Chief Medical Officer of Alumis.
• Dr. Jörn Drappa added that the depth of response and favorable safety profile support envudeucitinib’s potential to play a leading role among oral options for moderate-to-severe plaque psoriasis.
• Alumis is continuing to evaluate long-term efficacy and safety in ONWARD3 and plans to submit a U.S. NDA in the second half of 2026.
• A once-daily formulation and a pediatric development plan for envudeucitinib are under development.

Industry Context

StockSavvy.ai notes that these Phase 3 results position envudeucitinib as a leading oral contender in psoriasis. The efficacy (PASI 90 ~62–68% and PASI 100 ~39–41% at Week 24) appears to exceed outcomes historically reported for apremilast and may compare favorably to published Week 16 PASI 90 rates for Bristol Myers Squibb’s TYK2 inhibitor deucravacitinib, while still trailing top-tier biologics (e.g., IL-23/IL-17 agents) on absolute clearance rates. If replicated in real-world and long-term data, envudeucitinib could reshape the oral treatment segment.

Comparison to Industry Standards

• Versus apremilast (Otezla, Amgen): Envudeucitinib delivered markedly higher PASI 90 at Week 16 (~60%/53% vs ~21%/21%) and continued to deepen to ~62–68% by Week 24; scalp, itch, and DLQI improvements were also superior (all p<0.0001 at Week 16).
• Versus deucravacitinib (Sotyktu, Bristol Myers Squibb): Published POETYK PSO-1/2 Week 16 PASI 90 rates are approximately mid-30s to low-40s with PASI 100 in low-teens; envudeucitinib’s PASI 90 at Week 16 (53–60%) and PASI 100 (28–29%) appear higher on a cross-trial basis, though no head-to-head data are available.
• Versus leading biologics (e.g., risankizumab, guselkumab, secukinumab): Top biologics often report PASI 90 rates ~70–80%+ and PASI 100 ~40–50% by later timepoints; envudeucitinib’s Week 24 PASI 90 (~62–68%) and PASI 100 (~39–41%) approach lower bounds of biologic performance while retaining oral convenience.
• Safety profile: Absence of MACE/TB reactivation signals and low SAEs/discontinuations compare favorably to historical expectations for oral immunomodulators; long-term and post-marketing data will be important for full benchmarking.

Stakeholder Impact

• Patients: Early, deep, and broad improvements in skin clearance, itch, and quality of life suggest a potentially more effective oral option for moderate-to-severe psoriasis.
• Physicians: A high-efficacy oral agent with favorable safety could expand first-line systemic choices before progressing to biologics.
• Payers: Potential for cost-offsets if an oral option can reduce biologic utilization in some patients, pending pricing and real-world effectiveness.
• Shareholders: Positive Phase 3 data de-risks the program and sets up a clear regulatory path and multiple data catalysts in 2026.
• Competitors: Raises the performance bar for oral psoriasis therapies, intensifying competition in the TYK2 and broader immunology space.

Next Steps

• Submit a U.S. NDA for envudeucitinib in H2 2026.
• Deliver one-year Phase 3 long-term efficacy and safety data in H2 2026.
• Continue enrollment/follow-up in ONWARD3 long-term extension.
• Advance development of a once-daily formulation for envudeucitinib.
• Advance a pediatric development plan for envudeucitinib.
• Report topline data from the LUMUS Phase 2b SLE program in Q3 2026.
• Provide replay and materials from the Mar 29, 2026 investor webcast on the company website.

Key Dates

Recommendation

The dual Phase 3 success with strong PASI 90/100 rates, rapid onset, and a favorable safety profile materially advances envudeucitinib toward approval and commercial potential. While regulatory and long-term safety risks persist, the dataset is robust, comparisons vs apremilast are compelling, and multiple near-term catalysts (NDA in H2 2026; LTE and SLE readouts) support a constructive risk/reward.

Keywords

envudeucitinib, TYK2 inhibitor, plaque psoriasis, ONWARD1, ONWARD2, PASI 90, PASI 100, sPGA, DLQI, pruritus, scalp psoriasis, apremilast, AAD 2026, long-term extension, NDA, ONWARD3, systemic lupus erythematosus, LUMUS, safety, efficacy