LY4268989 / Schrodinger, Eli Lilly - LARVOL DELTA

GARNET: A Phase 2 Study to Evaluate MORF-057 in Adults With Moderately to Severely Active Crohn's Disease (clinicaltrials.gov) - P2 | N=385 | Recruiting | Sponsor: Morphic Therapeutic, Inc. (A Wholly Owned Subsidiary of Eli Lilly and Company) | N=164 ➔ 385

Enrollment change • Crohn's disease • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease

J6E-MC-KWAN: LY4268989 (MORF-057) Co-Administered with Mirikizumab in Adults with Moderately to Severely Active Ulcerative Colitis: A Phase 2 Study (clinicaltrialsregister.eu) - P1/2 | N=14 | Not yet recruiting | Sponsor: Eli Lilly & Co.

New P1/2 trial • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

J6E-MC-KWAN: LY4268989 (MORF-057) Co-Administered with Mirikizumab in Adults with Moderately to Severely Active Ulcerative Colitis: A Phase 2 Study (clinicaltrialsregister.eu) - P1/2 | N=5 | Not yet recruiting | Sponsor: Eli Lilly & Co.

New P1/2 trial • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

GARNET: A Phase 2 Study to Evaluate MORF-057 in Adults With Moderately to Severely Active Crohn's Disease (clinicaltrials.gov) - P2 | N=385 | Recruiting | Sponsor: Morphic Therapeutic, Inc. (A Wholly Owned Subsidiary of Eli Lilly and Company) | Trial completion date: Aug 2028 ➔ Jun 2030 | Trial primary completion date: Nov 2026 ➔ Sep 2028

Trial completion date • Trial primary completion date • Crohn's disease • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease

EMERALD-3: LY4268989 in Adults With Moderately to Severely Active Ulcerative Colitis (clinicaltrials.gov) - P2 | N=1431 | Not yet recruiting | Sponsor: Eli Lilly and Company

New P2 trial • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

MORF-057: Completion of P2 EMERALD-2 trial (NCT05611671) for moderately to severely active ulcerative colitis in Aug 2026 (Eli Lilly) - Q4 2025 Results: Primary completion of P2 GARNET trial (NCT06226883) for moderately to severely active Crohn's disease in Nov 2026; Completion of P2 GARNET trial for moderately to severely active Crohn's disease in Aug 2028

Trial completion date • Crohn's disease • Inflammatory Bowel Disease • Ulcerative Colitis

GARNET: A Phase 2 Study to Evaluate MORF-057 in Adults With Moderately to Severely Active Crohn's Disease (clinicaltrials.gov) - P2 | N=385 | Recruiting | Sponsor: Morphic Therapeutic, Inc. (A Wholly Owned Subsidiary of Eli Lilly and Company) | N=210 ➔ 385

Enrollment change • Crohn's disease • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease

TOPAZ-UC: LY4268989 (MORF-057) Co-Administered With Mirikizumab in Adults With Moderately to Severely Active Ulcerative Colitis: (clinicaltrials.gov) - P2 | N=252 | Recruiting | Sponsor: Eli Lilly and Company | Not yet recruiting ➔ Recruiting

Enrollment open • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

MORF-057: Primary completion of P2 TOPAZ-UC trial (NCT07186101) for moderate to severe ulcerative colitis in May 2027 (Eli Lilly) - Q3 2025 Results: Completion of P2 trial for moderate to severe ulcerative colitis in Mar 2029

Trial completion date • Trial primary completion date • Inflammatory Bowel Disease • Ulcerative Colitis

A Study of LY4268989 (MORF-057) in Healthy Participants (clinicaltrials.gov) - P1 | N=114 | Recruiting | Sponsor: Eli Lilly and Company | N=66 ➔ 114

Enrollment change

EFFICACY AND SAFETY OF MORF-057 THERAPY IN ADULTS WITH MODERATELY TO SEVERELY ACTIVE ULCERATIVE COLITIS: PHASE 2B EMERALD-2 STUDY RESULTS THROUGH WEEK 12 (UEGW 2025) - P2 | "Dose-dependent responses to MORF-057 were observed for clinical remission and hard-to-achieve endpoints such as HEMI at Week 12. The clinical remission rate with MORF-057 was numerically higher but did not achieve statistical significance vs. placebo, which showed higher-than-expected responses."

Clinical • P2b data • CNS Disorders • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Rare Diseases • Respiratory Diseases • Ulcerative Colitis

A Study of LY4268989 (MORF-057) in Healthy Participants (clinicaltrials.gov) - P1 | N=66 | Recruiting | Sponsor: Eli Lilly and Company | Trial completion date: Aug 2025 ➔ Dec 2025 | Trial primary completion date: Aug 2025 ➔ Dec 2025

Trial completion date • Trial primary completion date

TOPAZ-UC: LY4268989 (MORF-057) Co-Administered With Mirikizumab in Adults With Moderately to Severely Active Ulcerative Colitis: (clinicaltrials.gov) - P2 | N=252 | Not yet recruiting | Sponsor: Eli Lilly and Company

New P2 trial • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

MORF-057: Completion of P2 EMERALD-2 trial (NCT05611671) for moderately to severely active ulcerative colitis in Aug 2026 (Eli Lilly) - Q2 2025 Results: Primary completion of P2 GARNET trial (NCT06226883) for moderately to severely active Crohn's disease in Nov 2026; Completion of P2 GARNET trial for moderately to severely active Crohn's disease in Aug 2028

Trial completion date • Trial primary completion date • Crohn's disease • Inflammatory Bowel Disease • Ulcerative Colitis

Study of MORF 057 to Evaluate Single and Multi Ascending Doses in Healthy Volunteers (clinicaltrials.gov) - P1 | N=67 | Completed | Sponsor: Morphic Therapeutic, Inc. (A Wholly Owned Subsidiary of Eli Lilly and Company) | Phase classification: P1a ➔ P1

Phase classification

GARNET: A Phase 2 Study to Evaluate MORF-057 in Adults With Moderately to Severely Active Crohn's Disease (clinicaltrials.gov) - P2 | N=210 | Recruiting | Sponsor: Morphic Therapeutic, Inc. (A Wholly Owned Subsidiary of Eli Lilly and Company) | Trial primary completion date: Jul 2026 ➔ Nov 2026

Trial primary completion date • Crohn's disease • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease

A Phase 2 Study of MORF-057, an Oral α4β7 Integrin Inhibitor in Moderately to Severely Active Ulcerative Colitis. (PubMed, Clin Gastroenterol Hepatol) - P2 | "Overall, this study demonstrated that oral MORF-057 is well tolerated, with promising efficacy for individuals with moderately to severely active UC."

Journal • P2 data • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

A Study of LY4268989 (MORF-057) in Healthy Participants (clinicaltrials.gov) - P1 | N=66 | Recruiting | Sponsor: Eli Lilly and Company | Not yet recruiting ➔ Recruiting

Enrollment open

A Study of LY4268989 (MORF-057) in Healthy Participants (clinicaltrials.gov) - P1 | N=66 | Not yet recruiting | Sponsor: Eli Lilly and Company

New P1 trial

SERUM-BASED BIOMARKERS DIFFERENTIATE RESPONSE IN ULCERATIVE COLITIS PATIENTS TREATED WITH AN ORAL α4β7 INTEGRIN SMALL MOLECULE INHIBITOR MORF-057 (DDW 2025) - "Lower baseline levels of CPa9-HNE, C1M, and C7M in responders may indicate a potential association with patient response to MORF-057. Treatment-related changes in PRO-C3, C4M, and VICM may suggest that these biomarkers could serve as early indicators of efficacy. Collagen type III is associated with wound healing and higher levels of the N-terminal propeptide of type III collagen, PRO-C3, in responders could indicate potential mucosal healing 2 ."

Biomarker • Clinical • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis • ITGA4

MORF-057: Completion of P2 EMERALD-2 trial (NCT03157128) for ulcerative colitis in Aug 2026 (Eli Lilly) - Q1 2025 Results: Primary completion of P2 GARNET trial (NCT03157128) for ulcerative colitis in May 2026; Completion of P2 GARNET trial for Crohn's disease in June 2028

Trial completion date • Trial primary completion date • Crohn's disease • Inflammatory Bowel Disease • Ulcerative Colitis

Gut-directed therapeutics in inflammatory bowel disease. (PubMed, Curr Opin Gastroenterol) - "Gut-targeted therapies range from novel variations on traditional drugs (i.e., mAbs and small molecules) to microbiome-based therapeutics and engineered delivery systems. They can be used alone or in combination with currently available therapies. Future directions should focus on the development of tried-and-true modalities (mAbs, small molecules) as well as the microbiome and more innovative delivery systems."

Journal • Crohn's disease • Gastroenterology • Gastrointestinal Disorder • Gene Therapies • Immunology • Inflammation • Inflammatory Bowel Disease • Ulcerative Colitis

EMERALD-1: A Phase 2a Open-Label Study to Evaluate the Efficacy and Safety of MORF-057 in Adults With UC (clinicaltrials.gov) - P2 | N=35 | Completed | Sponsor: Morphic Therapeutic, Inc | Active, not recruiting ➔ Completed

Trial completion • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • Ulcerative Colitis

Changes in circulating lymphocyte subsets and CCR9 transcripts as mechanistic biomarkers of the small molecule α4β7 inhibitor MORF-057 in patients with Ulcerative Colitis (ECCO-IBD 2025) - P2 | "Effects observed were consistent with those reported for patients receiving biologic inhibitors of the same pathway as well as in healthy volunteers receiving MORF-057 1,2 . These changes in circulating lymphocyte populations and CCR9 transcript levels may be used as mechanistic biomarkers for MORF-057 in UC patients."

Biomarker • Clinical • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis • CD4

EMERALD-2: A Study to Evaluate MORF-057 in Adults with Moderately to Severely Active UC (clinicaltrials.gov) - P2 | N=280 | Active, not recruiting | Sponsor: Morphic Therapeutic, Inc | Recruiting ➔ Active, not recruiting | Trial completion date: Jul 2025 ➔ Aug 2026 | Trial primary completion date: May 2025 ➔ Dec 2024

Enrollment closed • Trial completion date • Trial primary completion date • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • Ulcerative Colitis