Disc Medicine presents clinical, translational data acroos portfolio at ASH meet

Disc Medicine (IRON) spotlights 8 posters presented at the ASH 2024 annual meeting in San Diego, CA. This year’s presentations included updates from the BEACON and AURORA trials of bitopertin in patients with erythropoietic protoporphyria and the Phase 1 SAD/MAD trial of DISC-3405 in healthy volunteers. Additionally, Disc presented a real-world patient survey highlighting the disease burden of EPP and multiple preclinical models highlighting the potential benefits of bitopertin, DISC-0974, and DISC-3405 in existing and new indications. The collection of data supports Disc’s continued advancement of all three clinical candidates and provides evidence for expansion opportunities in new indications. In addition to its poster presentations, Disc presented complete results from the Phase 1b trial of DISC-0974 in anemia of myelofibrosis yesterday, December 8, in an oral presentation. These results demonstrated positive impact on clinically meaningful measures of anemia across a broad range of patient types and support advancement of the program into a Phase 2 trial in MF anemia, which is now initiated. Bitopertin, DISC-0974, and DISC-3405 are investigational agents and are not approved for use as therapies in any jurisdiction worldwide. Bitopertin: Disc is advancing development and registrational activities for bitopertin in EPP, with the potential for accelerated approval using PPIX as a surrogate endpoint. AURORA: The AURORA study is a randomized, double-blind, placebo-controlled Phase 2 clinical trial that enrolled 75 adult subjects with EPP. Subjects were randomized 1:1:1 to receive 20 mg of bitopertin 60 mg of bitopertin, or placebo orally once daily for 17 weeks. Updated analyses show that bitopertin reduced PPIX in all prespecified subgroups across demographic and baseline patient characteristics; Previously presented analyses showed that reductions in PPIX were associated with improvements in multiple clinical outcomes, including measures of sunlight tolerance, reductions in phototoxic reactions, and patient-reported quality of life. BEACON: The BEACON study is a Phase 2, randomized, open-label, multiple dose clinical trial that enrolled 22 adults and 4 adolescents with EPP. Subjects were randomized 1:1 to receive 20 mg of bitopertin or 60 mg of bitopertin orally once daily for 24 weeks. Updated analyses show that bitopertin significantly reduced protoporphyrin IX at low and high doses and in both adult and adolescent populations; Bitopertin had a meaningful impact on light tolerance, with similar benefit shown across adult and adolescent populations; Reductions in PPIX were associated with improvements in multiple measures of sunlight tolerance; Bitopertin was generally well tolerated and showed a similar safety profile in adults and adolescents. EPP LIGHT Study: The EPP LIGHT Study is a patient survey study seeking to comprehensively describe the burden of disease in adults and adolescents with EPP. Across adult and adolescent respondents, EPP symptoms impact all facets of life including ability to be out in the sun for prolonged periods of time, ability to undertake daily activities, deficits in emotional functioning, and absenteeism at work and school; 68% of adults and 45% of adolescents experienced pain from a phototoxic reaction after less than30 minutes in direct sunlight, and recovery time was an average of 5.5 +/- 4.8 days for adults and 5.1 +/- 3.0 days for adolescents; 75% of adults and 46% of adolescents reported feeling depressed or sad and respondents reported substantially lower satisfaction with social roles and higher feelings of social isolation than the general population; 23% of employed adults reported missing work in the past month due to EPP; 24% of adults and 42% of adolescents attending school at the time of the study reported missing school in the past month due to EPP. Phototoxicity Study in Mouse Model of EPP: The effects of an orally bioavailable glycine transporter 1 inhibitor, DISC-C, on PPIX levels and skin phototoxicity induced by UV/blue light were evaluated in EPP mice. Results showed: Treatment with a mouse analog of bitopertin caused a 37-40% decrease in PPIX levels in red blood cells; GlyT1 inhibition significantly reduced skin lesions after light exposure; treated mice developed skin lesions in 9.2% of exposed skin area vs. 51.2% in placebo; Percentage of area with skin lesions correlated with PPIX levels, supporting PPIX as the pathological driver of phototoxicity in EPP