Late-Breaking Data at EADV of ESK-001, an Oral TYK2 Inhibitor for the Treatment of Psoriasis, Demonstrate Significant Responses with Sustained Increases Over 28 Weeks in Phase 2 OLE Study

Rhea-AI Summary

Alumis Inc. (Nasdaq: ALMS) announced positive 28-week data from the open-label extension (OLE) of its Phase 2 STRIDE trial for ESK-001, an oral TYK2 inhibitor for moderate-to-severe plaque psoriasis. The data, presented at the 2024 EADV Congress, showed:

- Dose-dependent sustained increases in PASI responses over time
- 93% of patients on 40 mg twice daily achieved PASI 75
- Favorable safety profile with mostly mild-to-moderate TEAEs
- Biomarker data supporting the 40 mg twice daily dose for Phase 3

The company expects to report full 52-week OLE data in 1H 2025 and is advancing ESK-001 in the Phase 3 ONWARD program. Additional presentations at EADV supported ESK-001's potential as a best-in-class treatment, showing improvements in quality of life and pruritus.

Positive

• 93% of patients achieved PASI 75 at the highest dose of 40 mg twice daily
• Dose-dependent sustained increases in PASI endpoint responses observed over time
• Favorable safety profile with majority of TEAEs being mild-to-moderate
• Biomarker data supports the 40 mg twice daily dose for maximal target inhibition
• Significant improvements in patient-reported quality of life and psoriasis-associated pruritus

Negative

• None.

Insights

Medical Research Analyst

The 28-week open-label extension (OLE) data for ESK-001 in psoriasis treatment shows promising results. At the highest dose of 40 mg twice daily, 93% of patients achieved PASI 75 (primary endpoint), with 72% reaching PASI 90. These efficacy rates are competitive with existing biologics, suggesting ESK-001 could be a potent oral alternative.

The dose-dependent response and sustained increases over time indicate a durable effect. Safety profile remains favorable, with mostly mild-to-moderate adverse events. The biomarker data supporting maximal target inhibition at 40 mg twice daily dose provides a strong rationale for the ongoing Phase 3 trial design.

While these results are encouraging, it's important to await the full 52-week data expected in 1H 2025 to assess long-term efficacy and safety. The improvement in quality of life measures (DLQI and pruritus NRS) adds clinical relevance to the efficacy endpoints.

Financial Analyst

Alumis Inc. (ALMS) is making significant progress with ESK-001, potentially positioning itself as a leader in the oral psoriasis treatment market. The positive Phase 2 OLE data strengthens the drug's commercial prospects, which could translate to substantial revenue potential given the large psoriasis market.

Key financial implications:

• Increased likelihood of Phase 3 success, reducing development risk
• Potential for premium pricing if efficacy proves comparable to biologics
• Large addressable market: moderate-to-severe plaque psoriasis affects millions globally
• Oral administration could capture market share from injectable biologics

With a market cap of $645 million, positive Phase 3 results could significantly boost Alumis' valuation. However, investors should consider the competitive landscape and potential pricing pressures in this crowded market. The full 52-week data in 2025 will be a important catalyst for the stock.

• 28-week data show ESK-001 was generally well tolerated and most patients treated with the top dose of 40 mg twice daily achieved PASI 75
  
• Three additional data presentations further support ESK-001’s potential to offer a highly differentiated and best-in-class treatment profile for people with moderate-to-severe plaque psoriasis
  
• Full 52-week Phase 2 OLE dataset expected 1H 2025; Phase 3 clinical program ongoing
  

SOUTH SAN FRANCISCO, Calif., Sept. 27, 2024 (GLOBE NEWSWIRE) -- Alumis Inc. (Nasdaq: ALMS), a clinical stage biopharmaceutical company developing oral therapies using a precision approach to optimize clinical outcomes and significantly improve the lives of patients with immune-mediated diseases, today announced positive 28-week data from the open-label extension (OLE) period of its Phase 2 STRIDE clinical trial of ESK-001. These data were presented during a late-breaking oral session at the 2024 European Academy of Dermatology & Venereology (EADV) Congress held September 25-29 in Amsterdam, Netherlands. ESK-001 is a highly selective allosteric oral tyrosine kinase 2 (TYK2) inhibitor currently being evaluated in the Phase 3 ONWARD clinical program for the treatment of moderate-to-severe plaque psoriasis.

“The OLE results continue to show that ESK-001 has the potential to safely and effectively inhibit the TYK2 target at the 40 mg twice daily dose and deliver lasting benefits that improve over time with continued treatment,” said Dr. Jörn Drappa, Alumis’ Chief Medical Officer. “These data reinforce our confidence in ESK-001’s potential as a best-in-class oral treatment for moderate-to-severe plaque psoriasis. We look forward to reporting the full 52-week OLE data in the first half of 2025 and continuing to advance ESK-001 in the Phase 3 ONWARD clinical program.”

The interim 28-week OLE data (as of March 1, 2024) showed dose-dependent sustained increases in Psoriasis Area and Severity Score (PASI) endpoint responses observed over time, with the majority of patients (93% as observed (AO, n=71), 82.7% using modified non-responder imputation (mNRI, n=81)) achieving PASI 75, the primary endpoint, at the highest dose of 40 mg twice daily.

	40 mg twice daily			40 mg once daily
	STRIDE Week 12	OLE Week 28		STRIDE Week 12	OLE Week 28
	NRI (N=39)	AO (N=71)	mNRI (N=81)	NRI (N=39)	AO (N=70)	mNRI (N=79)
PASI 75 (%)	64***	93	83	56***	73	67
PASI 90 (%)	39***	72	63	26***	47	44
PASI 100 (%)	15*	35	31	8	20	18
sPGA 0/1 (%)	59***	76	68	54***	54	51
*p<0.05, ***p<0.001 compared to placebo

ESK-001 continued to show a favorable safety profile in the OLE. Treatment emergent adverse event (TEAE) frequency and severity were similar across study arms, with the majority being mild-to-moderate and self-limited. In both the Phase 2 STRIDE clinical trial and the ongoing OLE, the most common TEAEs were upper respiratory tract infections, nasopharyngitis, and headaches.

Alumis presented three additional abstracts this week at EADV. An oral presentation highlighting biomarker data from the Phase 2 STRIDE clinical trial and an e-poster summarizing exploratory exposure response analyses from ESK-001 clinical trials present evidence indicating the 40 mg twice daily dose, which achieves maximal target inhibition according to blood and skin biopsy biomarkers, leads to the highest response rates. These findings support use of the 40 mg twice daily dose in the ongoing Phase 3 clinical program. Also, an e-poster described data that associated positive efficacy and safety outcomes in the Phase 2 STRIDE clinical trial and OLE with significant improvements in patients reported quality of life (DLQI) and psoriasis-associated pruritus (NRS) with clear, dose-dependent improvement observed.

Details of the EADV presentations can be found in the Publications section of the Alumis website.

About ESK-001 
Alumis’ lead clinical candidate, ESK-001, is a potent, highly selective allosteric tyrosine kinase 2 (TYK2) inhibitor that reduces signaling through several cytokine receptors including receptors for IL-12, IL-23, and IFN-a. ESK-001 is currently being evaluated in the Phase 3 ONWARD clinical program which consists of two identical global Phase 3, multi-center, randomized, double-blind placebo-controlled 24-week clinical trials, ONWARD1 and ONWARD2, designed to evaluate the efficacy and safety of ESK-001 in adult patients with moderate-to-severe plaque psoriasis. Each trial will enroll approximately 840 patients randomized 2:1:1 to receive either ESK-001 40 mg twice-daily, placebo or apremilast. The co-primary efficacy endpoints will be the proportion of patients with moderate-to-severe plaque psoriasis achieving PASI 75 and sPGA score 0/1 of ESK-001 compared to placebo at Week 16. Patients completing Week 24 will have the opportunity to participate in a long-term extension (LTE) trial, ONWARD3, that will evaluate durability and maintenance of response and long-term safety.

The Phase 3 clinical program is supported by positive data from the Phase 2 STRIDE clinical trial in which 228 patients were randomized to one of five ESK-001 dose cohorts or placebo. The trial met its primary endpoint, the proportion of patients achieving a PASI 75 at week 12 compared to placebo, and key secondary efficacy endpoints at all clinically relevant doses tested. Clear dose-dependent responses were observed with maximal efficacy and TYK2 inhibition achieved at the highest dose of 40 mg twice daily. ESK-001 was found to be generally well tolerated at all dose levels.

In parallel with the Phase 3 clinical program, Alumis is developing a once-daily modified release oral formulation of ESK-001 that can replace the current immediate release oral formulation that is dosed twice daily.

ESK-001 is also being evaluated in LUMUS, a Phase 2b clinical trial of ESK-001 for the treatment of patients with systemic lupus erythematosus. In addition, Alumis continues to leverage its precision data analytics platform to explore ESK-001’s potential application in other autoimmune indications.

About Alumis
Alumis is a clinical-stage biopharmaceutical company developing oral therapies using a precision approach to optimize clinical outcomes and significantly improve the lives of patients with immune-mediated diseases. Leveraging its proprietary precision data analytics platform, Alumis is building a pipeline of molecules with the potential to address a broad range of immune-mediated diseases as monotherapy or combination therapies. Alumis’ most advanced product candidate, ESK-001, is an oral, highly selective, small molecule, allosteric inhibitor of tyrosine kinase 2 that is currently being evaluated for the treatment of patients with moderate-to-severe plaque psoriasis and systemic lupus erythematosus. Alumis is also developing A-005, a CNS-penetrant, allosteric TYK2 inhibitor for the treatment of neuroinflammatory and neurodegenerative diseases. Beyond TYK2, Alumis’ proprietary precision data analytics platform and drug discovery expertise have led to the identification of additional preclinical programs that exemplify its precision approach. Incubated by Foresite Labs and led by a team of industry veterans experienced in small-molecule compound drug development for immune-mediated diseases, Alumis is pioneering a precision approach to drug development to potentially produce the next generation of treatment to address immune dysfunction.

Forward-Looking Statements
This press release contains forward-looking statements, including statements made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. These statements may be identified by words such as "aims," "anticipates," "believes," "could," "estimates," "expects," "forecasts," "goal," "intends," "may," "plans," "possible," "potential," "seeks," "will" and variations of these words or similar expressions that are intended to identify forward-looking statements. Any such statements in this press release that are not statements of historical fact may be deemed to be forward-looking statements. These forward-looking statements include, without limitation, statements regarding Alumis’ future plans and prospects, the potential for ESK-001 to be a best-in-class oral treatment for moderate-to-severe plaque psoriasis, any expectations regarding the safety, efficacy or tolerability of ESK-001, including based on the clinical update from Alumis’ OLE study, the ability of ESK-001 to treat moderate-to-severe plaque psoriasis and systemic lupus erythematosus, and the expected timing of Alumis’ 52-week OLE data. Any forward-looking statements in this press release are based on Alumis’ current expectations, estimates and projections only as of the date of this release and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. Readers are cautioned that actual results, levels of activity, safety, efficacy, performance or events and circumstances could differ materially from those expressed or implied in Alumis’ forward-looking statements due to a variety of risks and uncertainties, which include, without limitation, risks and uncertainties related to Alumis’ ability to advance ESK-001 and its other clinical candidates and to obtain regulatory approval of and ultimately commercialize Alumis’ clinical candidates, the timing and results of preclinical and clinical trials, Alumis’ ability to fund development activities and achieve development goals, Alumis’ ability to protect its intellectual property and other risks and uncertainties described in Alumis’ filings with the Securities and Exchange Commission (SEC), including any future reports Alumis may file with the SEC from time to time. Alumis explicitly disclaims any obligation to update any forward-looking statements except to the extent required by law.

FAQ

What were the key results of the ESK-001 Phase 2 OLE study for ALMS stock?

The 28-week data showed 93% of patients on 40 mg twice daily achieved PASI 75, with dose-dependent sustained increases in PASI responses over time. ESK-001 also demonstrated a favorable safety profile.

When will Alumis (ALMS) report the full 52-week OLE data for ESK-001?

Alumis expects to report the full 52-week Phase 2 OLE dataset for ESK-001 in the first half of 2025.

What is the current stage of clinical development for ESK-001 by Alumis (ALMS)?

ESK-001 is currently being evaluated in the Phase 3 ONWARD clinical program for the treatment of moderate-to-severe plaque psoriasis.

How did ESK-001 affect patient quality of life in the ALMS study?

The study data associated positive efficacy and safety outcomes with significant improvements in patient-reported quality of life (DLQI) and psoriasis-associated pruritus (NRS), showing clear, dose-dependent improvement.