LY4268989 / Schrodinger, Eli Lilly - LARVOL DELTA

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

Lilly Completes Acquisition of Morphic to Improve Outcomes and Expand Options for People Living with Inflammatory Bowel Disease (PRNewswire) - "Eli Lilly and Company...today announced the successful completion of its acquisition of Morphic Holding, Inc...Morphic is a biopharmaceutical company developing oral integrin therapies for treatment of serious chronic diseases, including a selective oral small molecule inhibitor of α4β7 integrin (known as MORF-057) for inflammatory bowel disease (IBD)...Lilly's tender offer to acquire all of the issued and outstanding shares of common stock of Morphic....at a purchase price of $57 per Share, net to the stockholder in cash, without interest thereon and subject to any applicable tax withholding, expired as scheduled at one minute past 11:59 p.m., Eastern time, on Aug. 15, 2024 and was not further extended."

M&A • Crohn's disease • Immunology • Inflammation • Inflammatory Bowel Disease • Ulcerative Colitis

Lilly to Acquire Morphic to Improve Outcomes for Patients with Inflammatory Bowel Disease (PRNewswire) - "Eli Lilly and Company...and Morphic Holding, Inc...announced a definitive agreement for Lilly to acquire Morphic, a biopharmaceutical company developing oral integrin therapies for treatment of serious chronic diseases. Morphic's lead program is a selective oral small molecule inhibitor of α4β7 integrin for the treatment of inflammatory bowel disease (IBD) that has the potential to improve outcomes and expand treatment options for patients. This molecule (known as MORF-057) is being evaluated in two Phase 2 studies in ulcerative colitis and one Phase 2 study in Crohn's disease."

M&A • Crohn's disease • 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=210 | Recruiting | Sponsor: Morphic Therapeutic, Inc | Trial primary completion date: Jul 2026 ➔ Apr 2026

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

Morphic Announces Corporate Highlights and Financial Results for the First Quarter 2024 (GlobeNewswire) - "Enrollment continued on target in EMERALD-2 Phase 2b trial of MORF-057 in ulcerative colitis...Anticipate dosing first patient in GARNET Phase 2 study of MORF-057 in patients with moderate-to-severe Crohn’s disease in second quarter...Research and development expenses were $42.4 million for the quarter ended March 31, 2024, as compared to $30.4 million for the same quarter last year. The increase was primarily attributable to higher development costs along with increased clinical trial costs to support phase 2 clinical studies and development activities for MORF-057, as well as other research costs to support early development candidates."

Commercial • Enrollment status • Trial status • Crohn's disease • 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=210 | Recruiting | Sponsor: Morphic Therapeutic, Inc | Not yet recruiting ➔ Recruiting

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

Morphic Announces Corporate Highlights and Financial Results for the Full Year 2023 (GlobeNewswire) - "EMERALD-1 Phase 2a trial of MORF-057 in UC:...Continued the 40-week maintenance phase of the EMERALD-1 study as planned, EMERALD-2 Phase 2b trial of MORF-057 in UC:...The primary endpoint of EMERALD-2 is clinical remission rate as measured by mMCS at 12 weeks and is expected to report in the first half of 2025; GARNET Phase 2 trial of MORF-057 in Crohn’s Disease: Announced that launch activities are underway for the randomized placebo-controlled GARNET Phase 2 study of MORF-057 in CD and that the study is anticipated to enroll its first patients in the first half of 2024...Research and development expenses were $140.4 million for the year ended December 31, 2023, as compared to $102.1 million for the year ended December 31, 2022. The increase was primarily attributable to higher development costs along with increased clinical trial costs to support phase 2 clinical studies and development activities for MORF-057..."

Commercial • P2b data • Trial status • Crohn's disease • 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=210 | Not yet recruiting | Sponsor: Morphic Therapeutic, Inc

New P2 trial • Crohn's disease • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease