Afamelanotide Acetate

Pursuing accelerated approval for bitopertin in EPP with protoporphyrin IX (PPIX) reduction as the surrogate endpoint Planning to submit NDA under accelerated approval pathway in H2 2025 based on existing clinical data, including results from BEACON and AURORA Phase 2 trials Achieved regulatory alignment on APOLLO post-marketing confirmatory trial design and on track to initiate trial by mid-year 2025 Aligned on average monthly time in light without pain during the last month of the 6-month treatment period and percent change from baseline in whole-blood metal-free PPIX after 6 months of treatment as coprimary endpoints for confirmatory trial Management will host a conference call on Tuesday, January 21 at 8:00 am EST. WATERTOWN, Mass., Jan. 21, 2025 (GLOBE NEWSWIRE) -- Disc Medicine, Inc. (NASDAQ:IRON), a clinical-stage biopharmaceutical company focused on the discovery, development, and commercialization of novel treatments for patients suffering from serious hematologic diseases, today announced positive feedback from its Type C meeting with the U.S. Food and Drug Administration (FDA) to discuss the APOLLO post-marketing confirmatory trial for bitopertin in EPP. “Our recent FDA interaction marks another step toward delivering a potentially life-altering therapy for EPP patients, and we appreciate the collaboration with regulators, our investigators, and the EPP patient community which has brought us to this point,” said John Quisel, J.D., Ph.D., President and Chief Executive Officer of Disc. “Last year, we aligned with the FDA on PPIX reduction as a surrogate endpoint for potential accelerated approval of bitopertin, and we are actively pursuing that path with plans to submit an NDA in the second half of 2025. As part of that process, the Type C meeting has provided further clarity on our plans for the APOLLO post-marketing confirmatory trial, which will kick off by the middle of this year and could eventually be the basis for converting an accelerated approval, if granted, to a full approval.” The meeting resulted in alignment on the design of the APOLLO post-marketing confirmatory trial. Key features include: Co-primary endpoints of average monthly total time in sunlight without pain between 10:00 and 18:00 during the last month of the 6-month treatment period and percent change from baseline in whole blood metal-free PPIX after 6 months of treatment; Other measures of efficacy such as occurrence of phototoxic reactions, cumulative total pain-free time in sunlight, patient global impression of change (PGIC), and time to prodrome; Selection of 60 mg dose of bitopertin and 6-month treatment duration; Inclusion of patients aged 12+ with EPP including X-linked protoporphyria (XLP); and Double-blind, placebo-controlled study with ~150 patients randomized 1:1. Disc plans to initiate the APOLLO trial by mid-2025 and will include sites in the US, Canada, Europe, and Australia. Based on guidance toward an NDA submission in H2 2025, Disc expects enrollment of the APOLLO trial to be well underway by the time of an accelerated approval, if granted. Management will host a call to discuss these updates on Tuesday, January 21 at 8:00 am EST. Please register for the event on the Events and Presentations page of Disc’s website (https://ir.discmedicine.com/). About Bitopertin Bitopertin is an investigational, clinical-stage, orally administered inhibitor of glycine transporter 1 (GlyT1) that is designed to modulate heme biosynthesis. GlyT1 is a membrane transporter expressed on developing red blood cells and is required to supply sufficient glycine for heme biosynthesis and support erythropoiesis. Disc is planning to develop bitopertin as a potential treatment for a range of hematologic diseases including erythropoietic porphyrias, where it has potential to be the first disease-modifying therapy. Bitopertin has been studied in multiple clinical trials in patients with EPP, including the Phase 2 open-label BEACON trial, the Phase 2 double-blind, placebo-controlled AURORA trial, and an open-label extension HELIOS trial. Bitopertin is an investigational agent and is not approved for use as a therapy in any jurisdiction worldwide. Disc obtained global rights to bitopertin under a license agreement from Roche in May 2021. About Erythropoietic Protoporphyria (EPP) Erythropoietic protoporphyria (EPP), including X-linked Protoporphyria (XLP), is a rare, debilitating and potentially life-threatening disease caused by mutations that affect heme biosynthesis, resulting in the accumulation of a toxic, photoactive intermediate called protoporphyrin IX (PPIX). This causes severe reactions when patients are exposed to sunlight, characterized by excruciating pain, edema, burning sensations and potential blistering and disfigurement. PPIX also accumulates in the hepatobiliary system and can result in complications including gallstones, cholestasis, and liver damage in 20-30% of patients and in extreme cases liver failure. Current standard of care involves extreme measures to avoid sunlight, including restricting outdoor activities to nighttime, use of protective clothing and opaque shields, and pain management. This has a significant impact on the psychosocial development, quality of life, and daily activities of patients, particularly in young children and families. There is currently no cure for EPP and only one FDA-approved therapy, a surgically implanted synthetic hormone designed to stimulate melanin production called Scenesse® (afamelanotide). About Disc Medicine Disc Medicine is a clinical-stage biopharmaceutical company committed to discovering, developing, and commercializing novel treatments for patients who suffer from serious hematologic diseases. We are building a portfolio of innovative, potentially first-in-class therapeutic candidates that aim to address a wide spectrum of hematologic diseases by targeting fundamental biological pathways of red blood cell biology, specifically heme biosynthesis and iron homeostasis. For more information, please visit www.discmedicine.com. Disc Cautionary Statement Regarding Forward-Looking Statements This press release contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995, including, but not limited to, express or implied statements regarding Disc’s expectations with respect to its potential APOLLO confirmatory clinical study of bitopertin in EPP and XLP patients, including the proposed study design, the anticipated timeline, and the results thereof; and the possible regulatory path forward for bitopertin in EPP, including whether the FDA will determine that the accelerated approval pathway continues to be appropriate, the treatment of the APOLLO clinical study as a post-marketing confirmatory trial, and the timeline for a potential NDA submission and accelerated approval, if granted, and whether the NDA submission will meet the standards of accelerated approval. The use of words such as, but not limited to, “believe,” “expect,” “estimate,” “project,” “intend,” “future,” “potential,” “continue,” “may,” “might,” “plan,” “will,” “should,” “seek,” “anticipate,” or “could” or the negative of these terms and other similar words or expressions that are intended to identify forward-looking statements. Forward-looking statements are neither historical facts nor assurances of future performance. Instead, they are based on Disc’s current beliefs, expectations and assumptions regarding the future of Disc’s business, future plans and strategies, clinical results and other future conditions. New risks and uncertainties may emerge from time to time, and it is not possible to predict all risks and uncertainties. No representations or warranties (expressed or implied) are made about the accuracy of any such forward-looking statements. Disc may not actually achieve the plans, intentions or expectations disclosed in these forward-looking statements, and investors should not place undue reliance on these forward-looking statements. Actual results or events could differ materially from the plans, intentions and expectations disclosed in the forward-looking statements as a result of a number of material risks and uncertainties including but not limited to: the adequacy of Disc’s capital to support its future operations and its ability to successfully initiate and complete clinical trials; the nature, strategy and focus of Disc; the difficulty in predicting the time and cost of development of Disc’s product candidates; Disc’s plans to research, develop and commercialize its current and future product candidates; the timing of initiation of Disc’s planned preclinical studies and clinical trials; the timing of the availability of data from Disc’s clinical trials; Disc’s ability to identify additional product candidates with significant commercial potential and to expand its pipeline in hematological diseases; the timing and anticipated results of Disc’s preclinical studies and clinical trials and the risk that the results of Disc’s preclinical studies and clinical trials may not be predictive of future results in connection with future studies or clinical trials and may not support further development and marketing approval; and the other risks and uncertainties described in Disc’s filings with the Securities and Exchange Commission, including in the “Risk Factors” section of its Annual Report on Form 10-K for the year ended December 31, 2023, and in its Quarterly Report on Form 10-Q for the quarterly period ended September 30, 2024. Any forward-looking statement speaks only as of the date on which it was made. None of Disc, nor its affiliates, advisors or representatives, undertake any obligation to publicly update or revise any forward-looking statement, whether as result of new information, future events or otherwise, except as required by law. Media Contact Peg Rusconi Deerfield Group peg.rusconi@deerfieldgroup.com Investor Relations Contact Christina Tartaglia Precision AQ christina.tartaglia@precisionaq.com

Dr Jasmin Barman-Aksӧzen speaking at the Outsourcing in Clinical Trials (OCT) DACH 2024 conference in Zurich, Switzerland. Credit: Jenna Philpott / GlobalData. When Dr Jasmin Barman-Aksӧzen began experiencing painful, unexplained burns on her skin, she turned to Wikipedia for answers. After discovering a possible diagnosis, she proposed it to her physician who confirmed that she had erythropoietic protoporphyria (EPP). This ultra-rare genetic disorder causes a phototoxic heme precursor to build up in the red blood cells, resulting in severe burn injuries on the skin after as little as ten minutes of exposure to visible light. At the time of her diagnosis, no treatment existed to alleviate or prevent the symptoms of EPP. “There was no cure, there was no therapy for the pain, and there were no preventive possibilities for this phototoxic reaction, so the only thing we could do was avoid visible light. As you can imagine, that’s socially very isolating, and it’s not compatible with a normal life, and having to avoid light also leads to depression. We sometimes see suicidal ideations,” she explained. Around the same time, Australia-based biotech Clinuvel Pharmaceuticals was in the process of developing afamelanotide – a slow-release treatment now known as Scenesse. The drug increases skin pigmentation and has anti-inflammatory properties, offering protection against light-induced skin damage. Speaking at the Outsourcing in Clinical Trials (OCT) DACH 2024 conference, taking place in Zurich, Switzerland, between 29 and 30 October, Barman-Aksӧzen explained that she joined a University of Zurich research group working on Scenesse as a PhD student. The treatment was already in Phase III trials, and she provided insights on clinical trial design and quality of life (QoL) measures for patients with EPP. See Also: Matinas BioPharma mulls wind-down as antifungal therapy deal falls through Amgen earns higher revenues in Q3 2024, puts rare diseases in the spotlight The results from the pivotal trial (NCT01605136) showed that patients receiving Scenesse could spend, on average, an additional 20 minutes in sunlight daily without experiencing pain, compared to those on a placebo. Maximally, the patients can spend up to three hours a day in sunlight while using the treatment. They also experienced fewer phototoxic reactions, with symptoms that were less intense and shorter in duration, leading to an overall improvement in quality of life. Though an additional 20 minutes of sun exposure a day may sound minimal, Barman-Aksӧzen highlighted how significant this can be for patients with EPP. Recalling a trip to Berlin, she shared that, without treatment, she wouldn’t have been able to take a taxi with a sunroof without risking a severe phototoxic reaction. “Those are the moments when we are really happy to have the treatment,” she explained. Data from this clinical trial led to Scenesse receiving European approval in 2014. Notably, Barman-Aksӧzen became the first patient to present directly to the European Medicines Agency (EMA) committee before its approval vote, offering insights that clarified both the condition and the treatment’s impact. The EMA subsequently announced that Scenesse was the first drug approved through a European pilot programme that incorporated patient and physician clinical experiences in regulatory decisions – an approach now more widely adopted. In 2019, the US Food and Drug Administration (FDA) followed with its own approval of the drug. Barman-Aksӧzen continues her work advocating for EPP patients and co-founded the International Porphyria Patient Network (IPPN) alongside other patient advocates. While Scenesse brought a treatment option to EPP patients, Barman-Aksӧzen underscored its limitations; it’s a fixed-dose implant for symptomatic relief, which is not scalable and cannot be used for children. Two new candidates, Mitsubishi’s dersimelagon and Disc Medicine’s bitopertin, are being evaluated in clinical trials. These trials present ethical challenges such as the potential for phototoxic burns in control groups, and the risk of a bias in patient selection, as more severely affected patients may hesitate to participate. Barman-Aksӧzen added: “As patients, we’ve requested head-to-head studies. Besides the ethical aspects, I, as a patient, want to know how a new substance compares not only to placebo but also to the existing therapy.”