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LY4268989

Phase 2

Ulcerative Colitis | Small molecule | Gastrointestinal |Eli Lilly and Company|Last Updated: Aug 21, 2026

Success Probability

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Trial Design

RandomizedDouble-BlindCONTROLLEDDMC
Total Trials1
Total Enrollment252

FDA Designations

No designations recorded

Clinical trial landscape

LY4268989 · 4 trials · 5 indications

Phase 2 2Phase 1 2
NCT07415044LY4268989 in Adults With Moderately to Severely Active Ulcerative ColitisUlcerative Colitis (UC)
RECRUITING1,431 Analytics
NCT07186101LY4268989 (MORF-057) Co-Administered With Mirikizumab in Adults With Moderately to Severely Active Ulcerative Colitis:Ulcerative Colitis
RECRUITING252 Analytics
PHASE2RECRUITING
LY4268989 in Adults With Moderately to Severely Active Ulcerative Colitis
Ulcerative Colitis (UC)Unlock trial analytics
PHASE2RECRUITING
LY4268989 (MORF-057) Co-Administered With Mirikizumab in Adults With Moderately to Severely Active Ulcerative Colitis:
Ulcerative ColitisUnlock trial analytics

Study Endpoints

Primary Endpoints

Percentage of Participants Who Achieve Clinical Remission with Modified Mayo Score (mMS)
Week 10
Percentage of Participants Who Achieve Clinical Remission with mMS Among Participants Who Achieved Clinical Response with LY4268989 at Week 10
Week 52
Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY4268989
Day 1 to Day 18
PK: Area Under the Concentration Curve (AUC) of LY4268989
Day 1 to Day 18
Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY4268989 (Cohort 1) and (Cohort 5)
Day 1 to Day 17
PK: Area Under the Concentration Curve (AUC) of LY4268989 (Cohort 1) and (Cohort 5)
Day 1 to Day 17
Number of Participants with Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) (Cohort 1), (Cohort 3), and (Cohort 5)
Baseline to Study Completion (Up to Day 17)

A summary of TEAEs, SAEs and other non-serious adverse events (AEs), regardless of causality, will be reported in the reported adverse events module

Number of Participants with TEAEs and SAEs (Cohort 4)
Baseline to Study Completion (Up to Period 4, Day 4)

A summary of TEAEs, SAEs and other non-serious adverse events (AEs), regardless of causality, will be reported in the reported adverse events module

PK: Cmax of LY4268989 (Cohort 2)
Day 1 to Day 13
PK: AUC of LY4268989 (Cohort 2)
Day 1 to Day 13
PK: AUC of Midazolam and 1'-Hydroxymidazolam (Cohort 3)
Day 1 to Day 17

PK of midazolam and 1'-hydroxymidazolam (AUC), where midazolam is administered alone and in the presence of LY4268989

PK: AUC of Midazolam and 1'-Hydroxymidazolam (Cohort 8)
Day 3 and Day 11

PK of midazolam and 1'-hydroxymidazolam (AUC), where midazolam is administered alone and in the presence of LY4268989

PK: Cmax of Midazolam and 1'-Hydroxymidazolam (Cohort 3)
Day 1 to Day 17

PK of midazolam and 1'-hydroxymidazolam (Cmax), when midazolam is administered alone and in the presence of LY4268989

PK: Cmax of Midazolam and 1'-Hydroxymidazolam (Cohort 8)
Day 3 to Day 11

PK of midazolam and 1'-hydroxymidazolam (Cmax), when midazolam is administered alone and in the presence of LY4268989

PK: Cmax of LY4268989 (Cohort 6)
Day 1 to Day 7
PK: AUC of LY4268989 (Cohort 6)
Day 1 to Day 7
PK: Cmax of LY4268989 (Cohort 7)
Day 1 to Day 12
PK: AUC of LY4268989 (Cohort 7)
Day 1 to Day 12

Secondary Endpoints

Percentage of Participants Who Achieve Clinical Response with mMS
Week 10
Percentage of Participants Who Achieve Clinical Response with mMS Among Participants Who Achieved Clinical Response with LY4268989 at Week 10
Week 10 Up to Week 52
Percentage of Participants Who Achieve Symptomatic Response
Baseline Up to Week 8
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Study Design & Arms

AllocationRANDOMIZED
MaskingDOUBLE
ModelPARALLEL
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
LY4268989 Study Dose 1EXPERIMENTALLY4268989 administered orally
LY4268989 Study Dose 2EXPERIMENTALLY4268989 administered orally
Placebo Study DosePLACEBO_COMPARATORPlacebo administered orally
LY4268989 + MirikizumabEXPERIMENTALLY4268989 administered orally (PO) + Mirikizumab administered intravenously (IV), then subcutaneously (SC). Responders will be re-randomized for Study Period 2.
Mirikizumab + LY4268989 PlaceboEXPERIMENTALMirikizumab administered IV, then SC + LY4268989 placebo administered PO. Responders and Non-responders will re-randomized for Study Period 2.
LY4268989 Treatment AEXPERIMENTALParticipants will receive LY4268989 single dose T1 orally with high-fat meal
LY4268989 Treatment BEXPERIMENTALParticipants will receive LY4268989 single dose T2 orally with high-fat meal
LY4268989 Treatment CEXPERIMENTALParticipants will receive LY4268989 single dose T2 orally in a fasted state
LY4268989 Treatment DEXPERIMENTALParticipants will receive LY4268989 single dose T3 orally with high-fat meal
LY4268989 Treatment EEXPERIMENTALParticipants will receive LY4268989 single dose T3 orally in a fasted state
LY4268989 Treatment FEXPERIMENTALParticipants will receive LY4268989 single dose T1 orally in a fasted state
LY4268989 or Placebo Cohort 1 (Blinded)EXPERIMENTALParticipants will receive LY4268989 orally or placebo single dose followed by BID administration
LY4268989 Cohort 2 (Open-Label)EXPERIMENTALParticipants will receive LY4268989 orally tablet (formulation compared to capsule formulation) in a fasted state
LY4268989 Cohort 3 (Open-Label)EXPERIMENTALParticipants will receive multiple doses of LY4268989 orally BID administration with midazolam orally and intravenously (IV).
LY4268989 or Placebo Cohort 4 (Blinded)EXPERIMENTALParticipants will receive single escalating doses of LY4268989 orally or placebo
LY4268989 Cohort 5 (Blinded)EXPERIMENTALParticipants will receive multiple doses of LY4268989 orally or placebo
LY4268989 Cohort 6 (Open-Label)EXPERIMENTALParticipants will receive LY4268989 single dose orally in a fasted and fed state
LY4268989 Cohort 7 (Open-Label)EXPERIMENTALParticipants will receive multiple doses of LY4268989 orally BID administration in a fed state
LY4268989 Cohort 8 (Open-Label)EXPERIMENTALParticipants will receive multiple doses of LY4268989 orally BID administration with midazolam IV in a fasted state.

Interventions

NameTypeDescription
LY4268989DRUGAdministered orally
PlaceboDRUGAdministered orally
MirikizumabDRUGAdministered IV then SC
LY4268989 PlaceboDRUGAdministered PO
MidazolamDRUGAdministered orally
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Eligibility Criteria

Age Range18 Years to 80 Years
SexALL
Healthy VolunteersNo
Study Sites259

Inclusion Criteria: * Have had an established diagnosis of ulcerative colitis (UC) for ≥3 months prior to randomization, which includes endoscopic evidence of UC * Have moderately to severely active UC defined by a Modified Mayo Score (mMS) of 5 to 9 with an Endoscopic Score (ES)≥2 confirmed by cen...

Countries:United StatesArgentinaBrazilCanadaChinaColombiaCroatiaCzechiaFranceGreeceHungaryIndiaIsraelItalyJapanLatviaLithuaniaMexicoPolandPortugalPuerto RicoSerbiaSlovakiaSouth AfricaSouth KoreaTaiwanTurkey (Türkiye)UkraineAustriaDenmarkGermanyNetherlandsRomaniaSpain
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Recent Changes (Last 90 Days)

LOWAug 21, 2026NCT07186101lastUpdatePostDate: changed
LOWAug 21, 2026NCT07415044lastUpdatePostDate: changed
LOWAug 21, 2026NCT07186101lastUpdatePostDate: changed
LOWAug 21, 2026NCT07415044lastUpdatePostDate: changed
LOWAug 20, 2026NCT07707375Status: NOT_YET_RECRUITING → RECRUITING
LOWAug 20, 2026NCT07707375Status: NOT_YET_RECRUITING → RECRUITING
LOWAug 6, 2026NCT07415044lastUpdatePostDate: changed
LOWAug 6, 2026NCT07186101lastUpdatePostDate: changed
LOWAug 6, 2026NCT07415044lastUpdatePostDate: changed
LOWAug 6, 2026NCT07186101lastUpdatePostDate: changed
LOWJul 17, 2026NCT07415044lastUpdatePostDate: changed
LOWJul 17, 2026NCT07186101lastUpdatePostDate: changed
LOWJul 17, 2026NCT07707375NEW_TRIAL: changed
LOWJul 17, 2026NCT07415044lastUpdatePostDate: changed
LOWJul 17, 2026NCT07186101lastUpdatePostDate: changed
LOWJul 17, 2026NCT07707375NEW_TRIAL: changed
LOWJul 17, 2026NCT07707375NEW_TRIAL: changed
LOWJul 7, 2026NCT07186101lastUpdatePostDate: changed
LOWJul 7, 2026NCT07415044lastUpdatePostDate: changed
LOWJul 7, 2026NCT07186101lastUpdatePostDate: changed

Frequently asked questions about LY4268989

What is LY4268989 used for?

LY4268989 is an investigational small molecule being studied for the treatment of moderately to severely active ulcerative colitis (UC) in adults. It is also being evaluated in healthy participants in early-phase studies to assess its safety and pharmacological properties.

Who makes LY4268989?

LY4268989 is being developed by Eli Lilly and Company, a pharmaceutical company traded on the NYSE under the ticker symbol LLY. The company is conducting clinical trials of this investigational drug in multiple countries.

What phase is LY4268989 in?

LY4268989 is in Phase 1 and Phase 2 clinical development. Phase 1 studies are evaluating the drug in healthy participants, while Phase 2 studies are assessing its efficacy and safety in adults with moderately to severely active ulcerative colitis.

What clinical trials is LY4268989 in?

LY4268989 is being studied in several clinical trials, including NCT06964776 and NCT07707375 in healthy participants, and NCT07186101 and NCT07415044 in adults with ulcerative colitis. The trials are being conducted in the United States and numerous other countries.

Is LY4268989 the same as MORF-057?

Yes, LY4268989 is also known as MORF-057. Clinical trial titles refer to the drug as LY4268989 (MORF-057), indicating that these names are used interchangeably for the same investigational compound.

Is LY4268989 FDA approved?

LY4268989 is not FDA approved. It is an investigational drug currently in clinical trials, including Phase 2 studies for ulcerative colitis. Its safety and efficacy have not yet been established, and it remains under clinical development.