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TVB-2640

Phase 2

KRAS Gene Mutation | Small molecule | Oncology |Sagimet Biosciences Inc. - Series A|Last Updated: May 22, 2026

Target and mechanism

Molecular targetFASN
Target classEnzyme
ModalitySmall molecule

Also known as [14C]-TVB-2640

Success Probability

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Market & Valuation

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Trial Design

UNCONTROLLEDDMCBiomarker
Total Trials1
Total Enrollment18

FDA Designations

No designations recorded

Clinical trial landscape

TVB-2640 · 6 trials · 8 indications

Phase 2 3Phase 1 3
NCT04906421Study of TVB-2640 in Subjects With Nonalcoholic Steatohepatitis (NASH)Metabolic Dysfunction-assocated Steatohepatitis/ Nonalcoholic Fatty Liver Disease
COMPLETED168 Analytics
NCT03808558Phase 2 Study of TVB-2640 in KRAS Non-Small Cell Lung CarcinomasKRAS Gene Mutation
ACTIVE NOT_RECRUITING18 Analytics
NCT03938246Study of TVB-2640 in Subjects With Non-Alcoholic Steatohepatitis (NASH)MASLD/MASH (Metabolic Dysfunction-Associated Steatotic Liver Disease / Metabolic Dysfunction-Associated Steatohepatitis)
COMPLETED142 Analytics
PHASE2COMPLETED
Study of TVB-2640 in Subjects With Nonalcoholic Steatohepatitis (NASH)
Metabolic Dysfunction-assocated Steatohepatitis/ Nonalcoholic Fatty Liver DiseaseUnlock trial analytics
PHASE2ACTIVE NOT_RECRUITING
Phase 2 Study of TVB-2640 in KRAS Non-Small Cell Lung Carcinomas
KRAS Gene MutationUnlock trial analytics
PHASE2COMPLETED
Study of TVB-2640 in Subjects With Non-Alcoholic Steatohepatitis (NASH)
MASLD/MASH (Metabolic Dysfunction-Associated Steatotic Liver Disease / Metabolic Dysfunction-Associated Steatohepatitis)Unlock trial analytics

Study Endpoints

Primary Endpoints

Histological Improvement in Nonalcoholic Fatty Liver Disease (NAFLD) Activity Score (NAS) Without Worsening of Fibrosis (by NASH Clinical Research Network [CRN] Fibrosis Score).
52 Weeks

Histological improvement is defined as ≥2 points improvement in NAS with ≥1 point improvement in ballooning or inflammation

Subjects With Resolution of Steatohepatitis and No Worsening of Liver Fibrosis by NASH CRN Fibrosis Score and Histological Improvement in NAS.
52 Weeks

NASH resolution defined as absence of fatty liver disease or isolated or simple steatosis without steatohepatitis and a score of either 0 or 1 for inflammation, 0 for ballooning and any value for steatosis and no worsening of liver fibrosis (by NASH CRN fibrosis score). Histological improvement defined as ≥2 point improvement in NAS (with ≥1 point improvement in ballooning or inflammation).

Disease Control Rate of TVB-2640
every 8 weeks through study completion, an average of 1 year

Determine Disease control rate of TVB-2640 in KRAS mutant NSCLC patients through RECIST and toxicity profile. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD), \>=20% increase in the sum of diameters of target lesions; Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.

Response Rate of TVB-2640
every 8 weeks through study completion, an average of 1 year

Determine response rate of TVB-2640 in KRAS mutant NSCLC patients through RECIST and toxicity profile. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD), \>=20% increase in the sum of diameters of target lesions; Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.

Percent Change in Hepatic Fat Fraction by Magnetic Resonance Imaging Proton Density Fat Fraction (MRI-PDFF) From Baseline
12 weeks

As determined by MRI-PDFF

Total TVB-2640 plasma concentration-time (AUC) at steady state
Day 4

Total TVB-2640 plasma concentration-time curve during a dosing interval at steady-state

Unbound TVB-2640 plasma concentration-time (AUC) at steady state
Day 4

Unbound TVB-2640 plasma concentration-time curve during a dosing interval at steady-state

Maximum plasma concentration (Cmax) for total TVB-2640 at steady state
Day 4
Maximum plasma concentration (Cmax) for unbound TVB-2640 at steady state
Day 4
incidence and severity of AEs
Screening to Day 7
[14C]TVB-2640: AUC-inf in plasma
Up to 22 days
[14C]TVB-2640: Amount excreted in urine
Up to 22 days
[14C]TVB-2640: Amount excreted in feces
Up to 22 days
To determine the maximum tolerated dose (MTD) based on toxicity analysis.
1.5 years

Toxicity will be monitored according to NCI - Common Toxicity Criteria for Adverse Events version (4.03). Patients receiving at least one dose of drug.

To determine the incidence and nature of dose-limiting toxicities (DLTs) of TVB-2640.
Days 1 to 21 of cycle 1 for monotherapy cohort(s); Days 1 to 28 of cycle 1 for combination with anti-cancer agent cohort(s)

Secondary Endpoints

Proportion of Subjects Experiencing Fibrosis Improvement of ≥1 Stage by NASH CRN Score Without Worsening of Steatohepatitis
52 Weeks
Proportion of Subjects Experiencing Resolution of Steatohepatitis and no Worsening of Liver Fibrosis (by NASH CRN Fibrosis Score)
52 Weeks
Proportion of Subjects With Improvement in Liver Fibrosis >=1 Stage by NASH CRN Fibrosis Score Without Worsening of Steatohepatitis at 52 Weeks OR Resolution of Steatohepatitis and No Worsening of Liver Fibrosis by NASH CRN Fibrosis Score
52 Weeks
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Study Design & Arms

AllocationRANDOMIZED
MaskingDOUBLE
ModelPARALLEL
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
TVB-2640 50 mgEXPERIMENTALSubjects will receive TVB-2640 PO QD for 52 weeks, with the first dose administered on Day 1.
PlaceboPLACEBO_COMPARATORSubjects will receive matching placebo PO QD for 52 weeks, with the first dose administered on Day 1.
TVB-2640EXPERIMENTALPatients will be administered TVB-2640 100mg/m2 orally once a day for 8 weeks.
TVB-2640 25 mg (US)EXPERIMENTALSubjects randomly assigned to receive the study drug will take TVB-2640 tablet orally every day for 12 week treatment period. The dose is to be taken at the same time of the day, with each dose separated by 24 hours (±4 hours).
TVB-2640 50 mg (US)EXPERIMENTALSubjects randomly assigned to receive the study drug will take TVB-2640 tablet orally every day for 12 week treatment period. The dose is to be taken at the same time of the day, with each dose separated by 24 hours (±4 hours).
Placebo (US)PLACEBO_COMPARATORSubjects randomly assigned to placebo will receive placebo tablets orally once a day under the same conditions and frequency as described for TVB-2640.
TVB-2640 50 mg (China)EXPERIMENTALSubjects randomly assigned to receive the study drug will take TVB-2640 tablet orally every day for 12 week treatment period. The dose is to be taken at the same time of the day, with each dose separated by 24 hours (±4 hours).
Placebo (China)PLACEBO_COMPARATORSubjects randomly assigned to placebo will receive placebo tablets orally once a day under the same conditions and frequency as described for TVB-2640.
TVB-2640 75 mg (US)EXPERIMENTALAfter completion of Cohorts 1 and 2, and if no stopping criteria are met upon review by the Independent SRC, an additional TVB-2640 75 mg open-label Cohort 3 will open in the US
TVB-2640 50 mg - normal hepatic functionEXPERIMENTALHealthy subjects with normal hepatic function receive 50 mg PO daily from Day 1 to Day 4
TVB-2640 50 mg - mild hepatic functionEXPERIMENTALSubjects with mild hepatic impairment will receive 50 mg PO daily from Day 1 to Day 4
TVB-2640 50 mg - moderate hepatic functionEXPERIMENTALSubjects with moderate hepatic impairment will receive 50 mg PO daily from Day 1 to Day 4
TVB-2640 50 mg - severe hepatic functionEXPERIMENTALSubjects with severe hepatic impairment will receive 50 mg PO daily from Day 1 to Day 4
Treatment Arm 1EXPERIMENTALSingle dose of TVB-2640, 50 mg, oral administration

Interventions

NameTypeDescription
TVB-2640DRUGOral dose, tablet
PlaceboOTHEROral dose, tablet
TVB-2640 25 mg (US)DRUGOral dose, tablet, daily dosing
TVB-2640 50 mg (US)DRUGOral dose, tablet, daily dosing
Placebo (US)DRUGOral dose, tablet, daily dosing
TVB-2640 50 mg (China)DRUGOral dose, tablet, daily dosing
Placebo (China)DRUGOral dose, tablet, daily dosing
TVB-2640 75 mg (US)DRUGOral dose, tablet, daily dosing
TVB-2640 - 50 mgDRUGTVB-2640 -50 mg administered orally once daily
[14C]-TVB-2640DRUG50 mg of TVB-2640 oral administration
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Eligibility Criteria

Age Range18 Years to N/A
SexALL
Healthy VolunteersNo
Study Sites117

Inclusion Criteria: * Must be willing and able to participate in the study and provide written informed consent. * Male and female adults ≥18 years of age on the date that written informed consent to take part in the study is provided. * Body mass index (BMI) ≥23 kg/m2 for Asians and ≥25 kg/m2 for ...

Countries:United StatesCanadaPolandPuerto RicoChinaHungaryUnited Kingdom
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Competitive Landscape -Genetic Mutations 6 trials (matched to "KRAS Gene Mutation")

Top 3 of 4 competitors

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Frequently asked questions about TVB-2640

What is TVB-2640?

TVB-2640 is an investigational small molecule drug developed by Sagimet Biosciences Inc. (ticker: SGMT). It has been studied in healthy volunteers and in patients with conditions including non-alcoholic steatohepatitis, MASLD/MASH, hepatic impairment, cirrhosis, KRAS gene mutation, and solid malignant tumors. It is not approved and remains in clinical development.

What does TVB-2640 target?

TVB-2640 targets FASN, an enzyme involved in fatty acid synthesis. By inhibiting this enzyme, the drug is designed to affect lipid production, which is relevant to liver conditions such as non-alcoholic steatohepatitis and MASLD/MASH, as well as to solid tumors with KRAS gene mutation.

Who makes TVB-2640?

TVB-2640 is developed by Sagimet Biosciences Inc., which trades under the ticker SGMT. The company is listed as the developer of the drug across its clinical program.

What phase is TVB-2640 in?

TVB-2640 is in Phase 1 development according to the current program status. It is an investigational drug and has not been approved by the FDA. Phase 2 studies have also been completed in non-alcoholic steatohepatitis and MASLD/MASH, but the drug remains in clinical development.

What clinical trials is TVB-2640 in?

TVB-2640 has been studied in completed trials including NCT05835180, a Phase 1 pharmacokinetic study in hepatic impairment; NCT05657834, a Phase 1 absorption, metabolism, and excretion study in healthy males; NCT04906421, a Phase 2 NASH study; and NCT03938246, a Phase 2 NASH study.

Is TVB-2640 the same as denifanstat?

Yes, TVB-2640 is also known as denifanstat. Other alternative names include TVB-2640 - 50 mg, [14C]-TVB-2640, and TVB-2640 25 mg (US). These refer to the same investigational compound developed by Sagimet Biosciences.