Ascletis Announces Positive Topline Results from Its Phase III Open-Label Study of Denifanstat (ASC40), a First-in-Class, Once-Daily Oral FASN Inhibitor for Acne

Ascletis (HKEX:1672) announced positive topline results from a Phase III open-label safety study of denifanstat (ASC40), a once-daily oral FASN inhibitor for moderate-to-severe acne.

Rhea-AI Summary

Ascletis (HKEX:1672) announced positive topline results from a Phase III open-label safety study of denifanstat (ASC40), a once-daily oral FASN inhibitor for moderate-to-severe acne. The 240-patient, 40-week trial reported a favorable safety and tolerability profile with mostly grade 1–2 TEAEs, no ASC40-related grade 3–4 AEs, no ASC40-related SAEs, and no deaths.

Ascletis also referenced a prior 480-patient randomized, double-blind Phase III trial that met all primary and key secondary endpoints in June 2025, and noted that a New Drug Application for ASC40 was recently accepted by the China National Medical Products Administration.

Positive

• NMPA accepted New Drug Application for denifanstat (ASC40)
• Open-label safety study enrolled 240 patients for 40 weeks
• No ASC40-related grade 3–4 adverse events reported
• Prior 480-patient randomized Phase III met all primary endpoints (June 2025)

Negative

• Open-label design limits efficacy interpretation compared with double-blind trials

Argus Jan 29 session

-8.45% close to close Open Argus

Details

News Market Reaction – SGMT

In the Jan 29 session, SGMT declined 8.45%, reflecting a notable negative market reaction.

Data tracked by StockTitan Argus on the day of publication.

Market Context

The stock moved -8.4% in the session following this news. A negative reaction despite favorable long...

Analysis

The stock moved -8.4% in the session following this news. A negative reaction despite favorable long-term safety echoes prior divergences, such as declines after positive clinical updates on Oct 14 and Dec 18, 2025. The market may have already priced in acne success following earlier Phase 3 and NDA news. With a Q3 $12.9M net loss and a $75.0M ATM available, financing expectations and broader biotech weakness could also have amplified downside pressure.

Key Figures

Open-label Phase 3 size: 240 patients Treatment duration: 40 weeks Serious safety events: 0 related grade 3/4 AEs or SAEs +5 more

Open-label Phase 3 size

240 patients

Moderate-to-severe acne study, all received denifanstat

Treatment duration

40 weeks

Once-daily denifanstat in Phase 3 open-label acne study

Serious safety events

0 related grade 3/4 AEs or SAEs

Phase 3 open-label denifanstat acne trial

Prior Phase 3 size

480 patients

Randomized placebo-controlled acne trial in China

Net loss

$12.9 million

Q3 2025 results

Cash & securities

$125.5 million

Balance as of September 30, 2025

ATM program size

$75.0 million

Established August 2025, no Q3 sales

Up-front license payment

$2.5 million

Paid to TAPI under resmetirom API license

Previous Clinical trial Reports

5 past events · Latest: Dec 18

Same Type 5 events

1. Dec 18

   Phase 1 PK data

   24h Move

   -4.9%

   Positive Phase 1 PK results for denifanstat–resmetirom combo with good tolerability.

2. Dec 10

   NDA acceptance China

   24h Move

   +0.6%

   China NMPA accepted NDA for denifanstat in moderate-to-severe acne.

3. Dec 10

   NDA acceptance detail

   24h Move

   +0.6%

   Ascletis detailed Phase 2/3 acne success and NMPA NDA acceptance for denifanstat.

4. Oct 24

   Phase 3 acne success

   24h Move

   +24.7%

   Phase 3 acne trial in China met all endpoints with favorable safety profile.

5. Oct 14

   Pre-NDA consultation

   24h Move

   -1.2%

   Ascletis completed pre-NDA consultation for denifanstat acne program with China NMPA.

24h Move is the share-price change in the day after each event; other market factors may also have contributed.

Key Terms

fatty acid synthase, FASN inhibitor, treatment-emergent adverse events, serious adverse events, +4 more

8 terms

fatty acid synthase medical

"Denifanstat (ASC40), a once-daily oral fatty acid synthase (FASN) inhibitor..."

Fatty acid synthase is a large enzyme that works like a molecular factory, stitching small carbon building blocks together to make long-chain fatty acids used by cells for energy, membranes and signaling. Investors care because abnormal activity of this enzyme is linked to cancers and metabolic diseases, making it a common drug and diagnostic target; changes in research or regulatory progress around it can affect the value of related biotech investments.

FASN inhibitor medical

"Denifanstat (ASC40), a once-daily oral fatty acid synthase (FASN) inhibitor..."

A FASN inhibitor is a drug that blocks the enzyme fatty acid synthase, which cells use to make fatty acids for building membranes and storing energy. Investors care because many cancers and metabolic diseases rely on this pathway, so these inhibitors are studied as potential therapies; success can boost drug-maker value while failures or safety problems can hurt it. Think of it as cutting off a factory’s raw-material supply to slow or stop a growing product line.

treatment-emergent adverse events medical

"The primary endpoints included: (1) incidence of treatment-emergent adverse events (TEAEs)..."

Events or symptoms that either appear for the first time or get worse after a patient starts a treatment; think of new or intensified side effects that show up once medicine or a medical device is used. Investors watch these closely because they affect whether a therapy can gain regulatory approval, be prescribed widely, or face legal and commercial setbacks—similar to how early customer complaints can sink a new product’s prospects.

serious adverse events medical

"(2) incidence of serious adverse events (SAEs); and (3) incidence of discontinuation..."

Serious adverse events are significant problems or negative outcomes that occur during a medical treatment or clinical trial, such as severe side effects, hospitalizations, or life-threatening conditions. They matter to investors because such events can impact a company's reputation, lead to regulatory scrutiny, or delay the development of new products, ultimately affecting the company’s financial performance.

New Drug Application regulatory

"New Drug Application for denifanstat (ASC40) for acne was recently accepted..."

A new drug application is a formal request submitted to government regulators seeking approval to market a new medicine. It is like a detailed proposal that shows the drug has been tested for safety and effectiveness. For investors, receiving approval signals that the drug may soon become available for sale, potentially leading to revenue growth and impacting the company's value.

de novo lipogenesis medical

"direct inhibition of sebum production, through inhibition of de novo lipogenesis (DNL)..."

De novo lipogenesis is the body’s process of turning excess sugars and carbohydrates into fatty acids and then storing them as fat, mainly in the liver and fat tissue. For investors, it matters because this pathway is a target for drugs, diagnostics and diet-based products aimed at obesity, fatty liver and diabetes; preventing or altering it can change treatment outcomes and market demand much like stopping a factory from producing surplus goods.

cytokine medical

"inhibition of inflammation, through decreasing cytokine secretion and Th17 differentiation."

Small proteins produced by cells that act as chemical messengers to coordinate immune and inflammatory responses, like text messages or traffic signals telling cells when to activate, calm down, or move. Investors care because cytokines are common drug targets and biomarkers; changes in cytokine activity can determine a therapy’s effectiveness, safety, regulatory approval, and market potential, so trial results or safety signals tied to cytokines often drive stock moves.

Th17 medical

"inhibition of inflammation, through decreasing cytokine secretion and Th17 differentiation."

Th17 are a subtype of white blood cells that help direct the body’s immune response, especially by promoting inflammation to fight infections. For investors, Th17 matters because excessive or misdirected Th17 activity is implicated in autoimmune and inflammatory diseases, making it a common target for drugs, diagnostics and biomarkers; think of them as a faucet that can either help put out a fire or, if stuck open, flood a room and cause damage.

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-  Denifanstat (ASC40), a once-daily oral fatty acid synthase (FASN) inhibitor, demonstrated favorable safety and tolerability in a Phase III open-label study

-  The exceptional efficacy of denifanstat (ASC40) observed in the Company's previously reported placebo-controlled Phase III trial coupled with a favorable safety profile in two Phase III trials provide a potential major break-through for the treatment of acne

-  New Drug Application for denifanstat (ASC40) for acne was recently accepted by the China National Medical Products Administration

HONG KONG, Jan. 29, 2026 /PRNewswire/ --  Ascletis Pharma Inc. (HKEX: 1672, "Ascletis") today announced positive topline results from the Phase III open-label study (NCT06248008) evaluating denifanstat (ASC40), a first-in-class, once-daily oral small molecule fatty acid synthase (FASN) inhibitor, in patients with moderate-to-severe acne vulgaris.

This recently completed second Phase III study was an open-label, multicenter study in China designed to evaluate the long-term safety of denifanstat (ASC40) in 240 patients with moderate to severe acne vulgaris. All the 240 patients, previously treated with denifanstat (ASC40) or placebo for 12 weeks, received denifanstat (ASC40) once daily for 40 weeks. The primary endpoints included: (1) incidence of treatment-emergent adverse events (TEAEs); (2) incidence of serious adverse events (SAEs); and (3) incidence of discontinuation due to adverse events (AEs). Denifanstat (ASC40) demonstrated a favorable safety and tolerability profile. Most TEAEs were mild (grade 1) and moderate (grade 2). There were no denifanstat (ASC40)-related grade 3 or 4 AEs and no denifanstat (ASC40)-related SAEs. No deaths were reported.

In June 2025, Ascletis announced that denifanstat (ASC40) met all primary, key secondary, and secondary endpoints in the 480-patient randomized, double-blind, placebo-controlled Phase III clinical trial (NCT06192264) for the treatment of moderate to severe acne vulgaris (Press Release).

The mechanisms of action of denifanstat (ASC40) for the treatment of acne are (1) direct inhibition of sebum production, through inhibition of de novo lipogenesis (DNL) in human sebocytes; and (2) inhibition of inflammation, through decreasing cytokine secretion and Th17 differentiation. Denifanstat (ASC40)'s unique mechanism of action directly reduces one of the main underlying causes of acne which is the overproduction of sebum. This sets denifanstat (ASC40) apart as most other acne treatments do not treat the underlying cause of the condition.

Denifanstat (ASC40) is licensed 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) and Ultra-Long-Acting Platform (ULAP) technologies as well as Peptide Oral Transport ENhancement Technology (POTENT), Ascletis has developed multiple drug candidates in-house, including both small molecules and peptides, such as 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; ASC36, a once-monthly subcutaneously administered amylin receptor peptide agonist, ASC35, a once-monthly subcutaneously administered GLP-1R/GIPR dual peptide agonist and ASC37, a GLP-1R/GIPR/GCGR triple peptide agonist for chronic weight management. Ascletis is listed on the Hong Kong Stock Exchange (1672.HK). For more information, 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 

View original content:https://www.prnewswire.com/news-releases/ascletis-announces-positive-topline-results-from-its-phase-iii-open-label-study-of-denifanstat-asc40-a-first-in-class-once-daily-oral-fasn-inhibitor-for-acne-302673868.html

SOURCE Ascletis Pharma Inc.

FAQ

AI-generated questions and answers. How Rhea-AI works. Not financial advice.

What did Ascletis (SGMT) announce about denifanstat (ASC40) on January 29, 2026?

Ascletis announced positive topline safety results from a 240-patient Phase III open-label study of denifanstat (ASC40). According to the company, the 40-week trial showed mostly grade 1–2 TEAEs, no ASC40-related grade 3–4 AEs, no ASC40-related SAEs, and no deaths.

How large and long was the Phase III open-label study of denifanstat (ASC40) reported by Ascletis (SGMT)?

The study enrolled 240 patients who received ASC40 daily for 40 weeks. According to the company, all participants had prior 12-week exposure to ASC40 or placebo before entering the long-term safety study.

Did the Phase III open-label study report serious adverse events for denifanstat (ASC40)?

No ASC40-related serious adverse events were reported in the open-label study. According to the company, there were no ASC40-related grade 3–4 adverse events and no deaths during the 40-week treatment period.

What earlier Phase III evidence supports denifanstat (ASC40) for acne before this open-label study?

Ascletis cited a randomized, double-blind, placebo-controlled 480-patient Phase III trial that met all primary and key secondary endpoints in June 2025. According to the company, that trial demonstrated exceptional efficacy for moderate-to-severe acne.

What is denifanstat (ASC40)'s mechanism of action for treating acne, as described by Ascletis (SGMT)?

Denifanstat inhibits fatty acid synthase to reduce sebum production and decreases inflammation via lower cytokine secretion and reduced Th17 differentiation. According to the company, this targets sebum overproduction, a main underlying cause of acne.

What regulatory progress has Ascletis (SGMT) reported for denifanstat (ASC40) in China?

Ascletis reported that a New Drug Application for denifanstat (ASC40) was accepted by the China National Medical Products Administration. According to the company, the acceptance advances the regulatory review pathway in Greater China.