Ascletis Presented Phase III Study Results of First-in-Class FASN Inhibitor Denifanstat (ASC40) for Acne Treatment in the Late Breaking News Sessions of the European Academy of Dermatology and Venereology (EADV) Congress 2025

Rhea-AI Summary

Ascletis presented successful Phase III clinical trial results for denifanstat (ASC40), a first-in-class FASN inhibitor for acne treatment, at EADV Congress 2025. The trial, involving 480 patients with moderate to severe acne vulgaris, demonstrated that denifanstat met all primary, key secondary, and secondary efficacy endpoints.

Key achievements include 33.17% treatment success versus 14.58% for placebo, 57.38% reduction in total lesion count, and 63.45% reduction in inflammatory lesions. The drug showed a favorable safety profile, with TEAEs comparable to placebo (58.6% vs 56.3%). Ascletis plans to submit an NDA to China's NMPA following encouraging pre-NDA consultation feedback.

Positive

• Met all primary, key secondary and secondary efficacy endpoints in Phase III trial
• Achieved 33.17% treatment success rate vs 14.58% for placebo
• Demonstrated significant lesion count reductions: 57.38% in total lesions and 63.45% in inflammatory lesions
• Showed favorable safety profile with mostly mild to moderate adverse events
• Received encouraging feedback from NMPA during pre-NDA consultation

Negative

• Higher incidence of dry skin (6.3% vs 2.9%) and xerophthalmia (5.9% vs 3.8%) compared to placebo
• Overall TEAEs rate slightly higher than placebo (58.6% vs 56.3%)

--Denifanstat (ASC40) met all primary, key secondary and secondary efficacy endpoints (ITT analysis) and significantly improved moderate-to-severe acne compared with placebo.

--Denifanstat (ASC40) demonstrated a favorable safety and tolerability profile. Treatment emergent adverse events (TEAEs) in the denifanstat (ASC40) group were comparable to placebo: 58.6% versus 56.3%. The majority of TEAEs were mild (Grade 1) or moderate (Grade 2).

--Pre-New Drug Application (NDA) consultation of denifanstat (ASC40) with the China National Medical Products Administration (NMPA) is ongoing and feedback received from NMPA so far is encouraging. Ascletis plans to submit an NDA for denifanstat (ASC40) for the treatment of moderate to severe acne vulgaris to NMPA after completing its pre-NDA consultation.

HONG KONG, Sept. 17, 2025 /PRNewswire/ -- Ascletis Pharma Inc. (HKEX: 1672, "Ascletis") announces today that the oral presentation of the Phase III study results of denifanstat (ASC40) for the treatment of moderate to severe acne vulgaris (NCT06192264) was presented in the Late Breaking News sessions of the European Academy of Dermatology and Venereology (EADV) Congress 2025 in Paris, France on September 17, 2025.

Details of the Oral Presentation

Title: First-in-Class FASN Inhibitor Denifanstat Achieved All Endpoints in the Treatment of Acne Vulgaris: Results from a Phase Ⅲ Randomised Placebo Controlled Trial

Presenter: Dr. Leihong (Flora) XIANG, M.D and Ph.D., Principal Investigator of denifanstat (ASC40) Phase III study, Department of Dermatology, Huashan Hospital, Fudan University

The Phase III clinical trial was a randomized, double-blind, placebo-controlled, multicenter clinical trial in China to evaluate the safety and efficacy of denifanstat (ASC40) once-daily oral tablet in 480 patients with moderate to severe acne vulgaris. Patients were enrolled and randomized into one active treatment arm and one placebo control arm at the ratio of 1:1 to receive 50 mg denifanstat (ASC40) oral tablet once daily or matching placebo for 12 weeks. Baseline characteristics were well balanced between denifanstat (ASC40) and placebo arms.

Primary endpoints included the percent treatment success, defined as an Investigator's Global Assessment (IGA) score of 0 (clear) or 1 (almost clear) with at least a 2-point decrease in IGA from baseline at week 12, the percent reductions from baseline to week 12 in total lesion count (TLC), and the percent reduction from baseline to week 12 in inflammatory lesion count (ILC).

After 4-week treatment, the denifanstat (ASC40) group already showed statistically significant improvements (p<0.05) over placebo in multiple efficacy endpoints, including treatment success, TLC, ILC, and non-inflammatory lesion count (NILC).

After 12-week treatment, denifanstat (ASC40) met all primary, key secondary and secondary efficacy endpoints. Table 1 summarizes efficacy results from the Phase III study versus placebo (intent-to-treat, ITT analysis). 

Table 1. Efficacy results from the Phase III study versus placebo (intent-to-treat, ITT analysis)

Efficacy endpoints (1)	50 mg denifanstat (ASC40), oral, once daily (n=240)	Placebo, oral, once daily (n=240)	Placebo adjusted	P value
Primary endpoints
Percent treatment success (2)	33.17	14.58	18.59	<0.0001
Percent reduction from baseline in TLC	57.38	35.42	21.96	<0.0001
Percent reduction from baseline in ILC	63.45	43.21	20.24	<0.0001
Key secondary endpoint
Percent reduction from baseline in NILC	51.85	28.94	22.91	<0.0001
Secondary endpoints
Absolute reduction from baseline in TLC	58.25	36.17	22.08	<0.0001
Absolute reduction from baseline in ILC	26.56	18.42	8.14	<0.0001

Notes:

(1)  All efficacy endpoints are least square means.

(2)  Treatment success is defined as an Investigator's Global Assessment (IGA) score of 0 (clear) or 1 (almost clear) with at least a 2-point decrease in IGA from baseline at week 12.

(3) TLC: total lesion count; ILC: inflammatory lesion count; NILC: non-inflammatory lesion count.

Denifanstat (ASC40) demonstrated a favorable safety and tolerability profile following 12 weeks of once-daily oral administration at 50 mg. The incidence rates of treatment-emergent adverse events (TEAEs) were comparable between denifanstat (ASC40) and placebo: 58.6% versus 56.3%. No incidence rates of TEAEs related to study drug in any category exceeded 10%. Only two categories of TEAEs had an incidence rate of more than 5% (6.3% dry skin in denifanstat (ASC40) -treated patients versus 2.9% in the placebo group; 5.9% xerophthalmia in denifanstat (ASC40) -treated patients versus 3.8% in the placebo group). The majority of TEAEs were mild (Grade 1) or moderate (Grade 2). All denifanstat (ASC40) -related TEAEs were mild (Grade 1) or moderate (Grade 2). There were no denifanstat (ASC40) -related Grade 3 or 4 TEAEs and no denifanstat (ASC40) -related serious AEs (SAEs). No deaths were reported. No denifanstat (ASC40) -related permanent treatment discontinuations or withdrawals were observed.

Detailed data presented at the EADV Congress 2025 can be found at Ascletis' website (link).

"Denifanstat (ASC40) is an innovative and potentially meaningful advancement for the treatment of acne and we're very pleased that we have presented these results to the dermatology community at this year's EADV Congress," said Jinzi Jason Wu, Ph.D., Founder, Chairman and CEO of Ascletis. "Denifanstat (ASC40) has a new mechanism of action for acne treatment and demonstrated statistically significant and clinically meaningful improvement compared to placebo in all primary and secondary endpoints in the Phase III study, as well as a favorable safety and tolerability profile."

Pre-New Drug Application (NDA) consultation of denifanstat (ASC40) with the China National Medical Products Administration (NMPA) is ongoing and feedback received from NMPA so far is encouraging. Ascletis plans to submit an NDA for denifanstat (ASC40) for the treatment of moderate to severe acne vulgaris to NMPA after completing its pre-NDA consultation.

Ascletis licensed denifanstat (ASC40) from Sagimet Biosciences Inc. (Nasdaq: SGMT) for exclusive rights in Greater China.

About Ascletis Pharma Inc.

Ascletis Pharma Inc. is a fully integrated biotechnology company focused on the development and commercialization of potential best-in-class and first-in-class therapeutics to treat metabolic diseases. Utilizing its proprietary Artificial Intelligence-Assisted Structure-Based Drug Discovery (AISBDD) Platform and Ultra-Long-Acting Platform (ULAP), Ascletis has developed multiple drug candidates in-house, including its lead program, ASC30, a small molecule GLP-1R agonist designed to be administered once daily orally and once monthly to once quarterly subcutaneously as a treatment therapy and a maintenance therapy for chronic weight management. Ascletis is listed on the Hong Kong Stock Exchange (1672.HK).

To learn more about Ascletis, please visit www.ascletis.com.

Contact：

Peter Vozzo
ICR Healthcare
443-231-0505 (U.S.)
Peter.vozzo@icrhealthcare.com

Ascletis Pharma Inc. PR and IR teams
+86-181-0650-9129 (China)
pr@ascletis.com
ir@ascletis.com

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SOURCE Ascletis Pharma Inc.

FAQ

What were the key results of Ascletis's Phase III denifanstat (ASC40) trial for acne treatment?

The trial met all endpoints with 33.17% treatment success vs 14.58% for placebo, showing 57.38% reduction in total lesions and 63.45% reduction in inflammatory lesions after 12 weeks of treatment.

How safe is denifanstat (ASC40) based on the Phase III clinical trial results?

Denifanstat showed a favorable safety profile with 58.6% TEAEs vs 56.3% for placebo. Most adverse events were mild or moderate, with no serious drug-related events or treatment discontinuations.

What is the mechanism of action of Ascletis's denifanstat (ASC40)?

Denifanstat (ASC40) is a first-in-class FASN inhibitor, representing a new mechanism of action for acne treatment.

What are the next steps for denifanstat (ASC40) regulatory approval?

Ascletis is currently in pre-NDA consultation with China's NMPA and plans to submit a New Drug Application for moderate to severe acne vulgaris treatment after completing the consultation.

How many patients participated in the Phase III trial of denifanstat?

The Phase III trial included 480 patients with moderate to severe acne vulgaris, randomized 1:1 to receive either 50 mg denifanstat or placebo daily for 12 weeks.