LY4268989 / Schrodinger, Eli Lilly - LARVOL DELTA

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

EMERALD-2: A Study to Evaluate MORF-057 in Adults With Moderately to Severely Active UC (clinicaltrials.gov) - P2 | N=280 | Recruiting | Sponsor: Morphic Therapeutic, Inc | Phase classification: P2b ➔ P2

Phase classification • Gastroenterology • Gastrointestinal Disorder • 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=40 | Active, not recruiting | Sponsor: Morphic Therapeutic, Inc | Phase classification: P2a ➔ P2

Phase classification • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • Ulcerative Colitis

Morphic Announces Corporate Highlights and Financial Results for the Third Quarter 2023 (GlobeNewswire) - "EMERALD-2 global Phase 2b randomized, double-blind, placebo-controlled trial of MORF-057 in patients with moderate-to-severe UC continues to enroll as projected: The primary endpoint of EMERALD-2 is the clinical remission rate as measured by mMCS at 12 weeks and is expected to report in the first half of 2025. The Phase 2b study of MORF-057 in Crohn’s Disease is anticipated to begin in the first half of 2024...Research and development expenses were $34.4 million for the quarter ended September 30, 2023, as compared to $25.2 million for the same quarter last year. The increase was primarily attributable to higher manufacturing and development costs along with higher pre-clinical and phase 2 clinical trial costs to support our lead product candidate, MORF-057."

Commercial • Enrollment status • New P2b trial • P2b data • Crohn's disease • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

Morphic Therapeutic to Host Webcast to Present EMERALD-1 Full Data Set (GlobeNewswire) - "Morphic Therapeutic...announced it will host a webcast and conference call to discuss the complete results from the open-label EMERALD-1 Phase 2a study of MORF-057 in adults with moderate to severe ulcerative colitis. The positive topline results from EMERALD-1 were reported in April of this year and the full data set will be presented at the upcoming UEG Week 2023."

P2a data • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

Morphic to Present Positive EMERALD-1 Phase 2a Data for MORF-057 in Patients with Moderate to Severe Ulcerative Colitis in Abstract for UEGW 2023 (GlobeNewswire) - "Morphic Therapeutic...today announced the publication of an abstract discussing new EMERALD-1 phase 2a primary results. The data is included in an abstract for a moderated poster presentation that will be presented by Bruce Sands, MD, MS....Moderated Poster Presentation Information: Clinical proof of principle and favorable tolerability profile shown with orally dosed MORF-057 as induction therapy for moderately to severely active UC: Phase 2a from EMERALD-1 study results. Presenter: Bruce Sands, MD, MS..."

CLINICAL PROOF OF PRINCIPLE AND FAVORABLE TOLERABILITY PROFILE SHOWN WITH ORALLY DOSED MORF-057 AS INDUCTION THERAPY FOR MODERATELY TO SEVERELY ACTIVE UC: PHASE 2A EMERALD-1 STUDY RESULTS (UEGW 2023) - "Introduction: Specific antagonism of α4β7 by the monoclonal antibody vedolizumab is a proven mechanism for IBD treatment1. MORF-057 demonstrated desired PK and PD profile. Consistent changes in key efficacy outcomes including statistically significant outcome in the primary endpoint observed. MORF-057 was well tolerated."

Clinical • P2a data • Anemia • Gastroenterology • Gastrointestinal Disorder • Hematological Disorders • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

25% of Patients Achieve Endoscopic Remission in Phase 2a EMERALD-1 Trial for MORF-057 (HCPLive) - "'There are three desired attributes in an IBD treatment: favorable safety profile, meaningful clinical efficacy, and oral route of administration. Currently approved IBD treatments achieve at most two of these qualities and force patients to compromise; we need a new option to treat IBD patients that combines a high rate of clinical remission with a favorable safety profile in oral formulation,' commented Bruce Sands, MD, MS..."

Media quote

Morphic to Present Positive EMERALD-1 Phase 2a Data for MORF-057 in Patients with Moderate to Severe Ulcerative Colitis in Abstract for UEGW 2023 (GlobeNewswire) - P2a | N=40 | EMERALD-1 (NCT05291689) | Sponsor: Morphic Therapeutic, Inc | "Morphic Therapeutic...announced the publication of an abstract discussing new EMERALD-1 phase 2a primary results. The data is included in an abstract for a moderated poster presentation that will be presented by Bruce Sands, M.D., M.S., at United European Gastroenterology Week (UEGW) 2023 in Copenhagen, Denmark....MORF-057 achieved the primary endpoint and demonstrated clinically meaningful improvements across secondary and exploratory measures. The mean Robarts Histopathology Index (RHI) score from baseline to week 12 was -6.4 (p=0.0019). Patients also demonstrated a reduction in modified Mayo Clinic Score (mMCS) from baseline to week 12 of -2.3 and 25.7% of patients achieved mMCS clinical remission....Pharmacokinetic (PK)/Pharmacodynamic (PD) evaluations confirmed results seen in healthy volunteer studies, showing trough drug concentrations leading to a median α4β7 receptor occupancy (RO) >99%."

P2a data • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

Morphic Announces Corporate Highlights and Financial Results for the Second Quarter 2023 (GlobeNewswire) - "Morphic Therapeutic...reported corporate highlights and financial results for the second quarter of 2023...Ongoing MORF-057 EMERALD Phase 2 Development Program Updates...Continued the 40-week maintenance phase of the EMERALD-1 study as projected with top-line data anticipated in the first half of 2024...Announced completion of enrollment in the exploratory cohort of the EMERALD-1 study comprised of UC patients who have previously failed treatment with vedolizumab...The primary endpoint of EMERALD-2 is the clinical remission rate as measured by mMCS at 12 weeks and is expected to report in the first half of 2025; Announced that the Phase 2b study of MORF-057 in Crohn’s Disease is anticipated to begin in the first half of 2024...Morphic strengthened its balance sheet with a total of approximately $345 million in new capital during the second quarter..."

Commercial • New P2b trial • P2a data • P2b data • Crohn's disease • 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) - P2a | N=40 | Active, not recruiting | Sponsor: Morphic Therapeutic, Inc | Recruiting ➔ Active, not recruiting | Trial completion date: Nov 2024 ➔ Feb 2025

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