Ab1196 Baseline Demographics and Disease Characteristics in Subjects With Ild in a Phase 2 Study to Evaluate Efficacy, Safety, and Tolerability of Mt-7117 in Diffuse Cutaneous Systemic Sclerosis

Background: Dersimelagon (MT-7117), a novel oral selective melanocortin-1 receptor agonist, is a potential therapeutic agent for the treatment of systemic sclerosis (SSc). MT-7117 demonstrated disease-modifying effects in preclinical models of SSc by reduction of skin thickness and lung fibrosis. MT-7117-G02 (NCT04440592) is a Phase 2, multicenter, randomized, double-blind, placebo-controlled, 52-week parallel-group study to evaluate the efficacy and safety of MT-7117 in subjects with diffuse cutaneous SSc (dcSSc). Objectives: Evaluate the demographics, baseline disease characteristics, and selected biomarkers of progression of interstitial lung disease (SSc-ILD) in subjects randomized in the MT-7117-G02 study by the presence or the absence of SSc-ILD. Methods: 76 eligible subjects in 8 countries (North America and Europe) were randomized 1:1 to either MT-7117 QD or placebo and stratified by the autoantibody status of anti-RNA Polymerase III at screening (positive or negative). The primary endpoint is the American College of Rheumatology Combined Response Index in diffuse cutaneous Systemic Sclerosis (ACR CRISS) composite score at Week 52. The study included subjects with dcSSc, age ≥ 18 years, and a disease duration ≤ 5 years who were on a stable standard of care treatment. The subjects were also required to have a baseline Modified Rodnan skin score (mRSS) of 15-45 units and predicted percent forced vital capacity (ppFVC) > 50%. Forty-two (55.3%) of all randomized subjects had evaluation of SSc-ILD diagnosed either by high resolution computed tomography (HRCT) or by medical history and clinical assessment of SSc-ILD; of those 11 (26.2 %) subjects were SSc-ILD+ and 28 (66.7%) subjects were SSc-ILD- and the status of 3 (7.1%) subjects was not available. Twenty-four (31.6%) of randomized subjects had HRCT 220 days (median) before screening or during the study; of those 9 (37.5%) subjects were SSc-ILD+ and 15 (62.5%) subjects were SSc-ILD-. Biomarkers of ILD progression including surfactant protein D (SP-D) at baseline were analyzed using ELISA. Results: Approximately 1/3 of the randomized subjects who had either available data of solely clinical (11 26.2%) or both clinical and HRCT (9 37.5%) assessments were diagnosed with SSc-ILD+. There were no major differences in age, gender, or race between the SSc-ILD+ and SSc-ILD- subjects in both diagnostic subgroups (Table 1). Disease duration was slightly longer in SSc-ILD+ subjects compared to SSc-ILD-. SSc-ILD+ subjects had a lower rate of RNA poly-positive antibodies, however, consistent with previous reports, the rate of positive Anti-Scl-70 autoantibodies was higher. Furthermore, SSc-ILD+ subjects had higher rates of abnormal levels of SP-D compared to SSc-ILD- subjects. Likewise, average SP-D levels were higher in SSc-ILD+ subjects compared to SSc-ILD- subjects. All SSc-ILD+ subjects were receiving baseline immunosuppressant (IS) treatment, while a slightly lower percentage of SSc-ILD- subjects were receiving baseline IS. MMF was the most common IS, followed by MTX in both subgroups. There were no differences between ILD subgroups in severity of skin manifestations by mRSS. Mean Dlco was slightly lower in SSc-ILD+ subjects, however, no difference in pp FVC% was observed between the subgroups. Conclusion: Randomized subjects (SSc-ILD+ and SSc-ILD-) were homogenous in demographics, baseline mRSS, ppFVC%, and concomitant IS. A large percentage of patients were not assessed for ILD and ILD may be missed in early dcSSc (Khanna D, Denton CP, 2021). The topline data of MT-7117 G02 will be available early 2024 and will assess the efficacy of MT-7117 to prevent disease progression in the subjects with SSc ILD+ and SSc-ILD-. REFERENCES: 1 Khanna D and Denton CP. The Lancet Respiratory Medicine. 2021;9(6): 560-62 https://doi.org/10.1016/ S2213-2600(21)00163-6. Acknowledgements: NIL. Disclosure of Interests: Dinesh Khanna AbbVie, Amgen, Boehringer Ingelheim, Genentech/Roche, GlaxoSmithKline, Horizon Therapeutics, Mitsubishi Tanabe Pharma, Sanofi-Aventis, United Therapeutics, AstraZeneca, Bayer, Bristol-Myers Squibb, Horizon Therapeutics, Immune Tolerance Network, National Institutes of Health, Pfizer, Patricia Carreira Janssen, Lilly, VivaCell, Emerald Health Pharmaceuticals, Gesynta Pharma, Boehringer Ingelheim, AbbVie, Sanofi Genzyme, Mitsubishi Tanabe,, Lorinda Chung Mitsubishi Tanabe, Eicos Sciences, Genentech, Kyverna, IgM Biosciences, Lillyand Jannsen, Boerhinger Ingelheim, Christopher P Denton Janssen, Boehringer Ingelheim, GSK, Boehringer Ingelheim, CSL Behring, Corbus, Roche, Gesynta, Mitsubishi Tanabe, Servier, GSK, Arxx Therapeutics, Horizon,, Marco Matucci-Cerinic Actelion, Janssen, Inventiva, Bayer, Biogen, Boehringer, CSL Behring, Corbus, Galapagos, Mitsubishi Tanabe, Samsung, Regeneron, Acceleron, MSD, Chemomab, Lilly, Pfizer, Roche,, MSD, Gabriela Riemekasten Boehringer Ingelheim, Boehringer Ingelheim, Mitsubishi Tanabe pharma America., Yoshiari Yanai Mitsubishi Tanabe pharma America., Songjie Cai Mitsubishi Tanabe Pharma America, Inc., Masaya Inagaki Mitsubishi Tanabe Pharma corporation, Nissim Sasson NStat solutions, Tanya Bogoslovsky Mitsubishi Tanabe Pharma America, Inc.