AM-1476

LUND, Sweden, Feb. 05, 2024 (GLOBE NEWSWIRE) -- AnaMar, a clinical-stage biotech company developing first-in-class anti-fibrotic 5-HT2B receptor antagonists, announces that the European Medicines Agency (EMA) and the United States Food and Drug Administration (FDA) have granted orphan drug designation (ODD) to its lead clinical candidate, AM1476 for the treatment of systemic sclerosis (SSc). AM1476 is a selective peripheral-acting 5-HT2B receptor small molecule antagonist that can be delivered orally. It has demonstrated efficacy in in vitro and in vivo models of fibrosis, as well as favourable safety and pharmacokinetic profiles in Phase I clinical studies. AM1476 offers a unique dual-action approach to treat both skin and lung manifestations of systemic sclerosis. Systemic sclerosis is a chronic, progressive, autoimmune disease characterized by inflammation and fibrosis, i.e. uncontrolled scar tissue formation, in skin and various internal organs. Skin fibrosis is the distinguishing hallmark of SSc, associated with significant disability. The degree of skin fibrosis provides insight about progression of the disease. Interstitial lung disease (ILD) is a common and early manifestation of SSc. Around 100,000 people in the EU are affected by SSc and up to 80% of these may develop ILD. ILD causes progressive lung scarring, known as fibrosis, which leads to increasing, chronic, breathing problems and organ dysfunction, and can lead to death. There are currently no treatments on the market that effectively stop or reverse scarring in both skin and lung tissue. AnaMar's Chief Executive Officer, Dr. Ulf Ljungberg, said: “We are delighted with the FDA’s and EMA’s decisions to grant orphan drug designation to AM1476 for SSc. This is a significant milestone and underscores the significant unmet need for novel medicines to prevent, heal and slow organ scarring from fibrotic diseases, which are often progressive and can have a poor prognosis. There is great potential in AM1476 as a unique dual-action approach to treat skin and lung manifestations of systemic sclerosis, especially as it represses both macrophage and fibroblast activity, whilst minimizing side effects and interactions with other medicines. We are now planning for Phase II clinical trials and look forward to commercialising our product with a pharma partner to bring better treatment options to patients with fibrosis.” The company has designed a Phase II study to evaluate the treatment effects in SSc-ILD with a proposed dosing regimen for 60 patients in a double-blinded, placebo-controlled randomized trial over 12 months with lung function and skin thickness as efficacy readouts. Drawing on its heritage in diagnostics, the company is also developing biomarkers and gene signatures to identify patients most likely to respond to treatment and ensure the best outcomes for patients with fibrosis. The FDA and EMA grant orphan status to products intended to treat, diagnose, or prevent a life-threatening rare disease or condition that affects fewer than five in 10,000 people in Europe, or under 200,000 people in the US, and with either no currently approved method of diagnosis, prevention, or treatment, or with significant benefit to those affected by the disease. Orphan drug designation provides certain benefits, including the potential for extensive marketing exclusivity following regulatory approval, reduction in regulatory fees and, in the case of EU, a centralized approval process. About AnaMar Based in Lund, Sweden, AnaMar is developing first-in-class, anti-fibrotic medicines through its patented suite of serotonin (5-HT2B) receptor antagonists. Our selective, oral 5-HT2B receptor antagonist, AM1476, has broad therapeutic potential across fibrotic conditions with limited, if any, treatment options, including systemic fibrotic disorders and organ-specific fibrotic disorders such as interstitial lung diseases. AM1476 offers a unique dual-action approach to treat skin and lung manifestations of systemic sclerosis. By targeting peripheral 5-HT2B receptors our antagonists will halt key signaling pathways associated with fibrosis. This specifically reduces 5-HT-induced myofibroblast and macrophage activity and TGF-β production, minimizing side effects and interactions with other medicines. We are combining our innovative therapeutic platform with biomarkers and genetic analysis to identify those patients most likely to benefit from treatment, using our heritage in diagnostics to ensure the best outcomes for those with fibrosis. We are currently seeking collaborations with pharma for the advancement of AM1476 into Phase II clinical trials. AnaMar’s leadership team has an experienced track record in discovery, development, and advancement of new medicines. The company has received significant funding over recent years from the Allegro Investment Fund. Media Contacts AnaMar Ulf Ljungberg – CEO ulf.ljungberg@anamar.com Scius Communications Katja Stout Tel: +44 7789 435 990 katja@sciuscommunications.com Daniel Gooch Tel: +44 7747 875 479 daniel@sciuscommunications.com

Not only is skin hardened in systemic sclerosis, but internal organs are also affected too. Image credit: Shutterstock/Numstocker. AnaMar has received orphan drug designations for its systemic sclerosis candidate AM1476 from the FDA and the EMA. The Swedish biotech is now eligible for several incentives in the two regions, according to the designations. Both agencies will provide regular feedback during the application process and waive certain fees. The FDA also offers seven years of market exclusivity while the EMA promises ten years of protection from competition. AnaMar’s AM1476 is an oral antagonist of the 5-hydroxytryptamine receptor (5-HT2B) receptor, which is also known as a serotonin receptor. The company says its candidate halts key signalling pathways associated with fibrosis in a 5 February press release. Systemic sclerosis , also known as scleroderma, is a progressive autoimmune disease characterised by inflammation and fibrosis. Not only is skin hardened in this condition, but internal organs can be affected too. Interstitial lung disease (ILD) is one of the most common disease consequences, occurring in approximately 80% of patients. Though no approved therapies are treating the underlying cause of the disease, the FDA has approved drugs that manage associated complications. Boehringer Ingelheim’s Ofev (nintedanib) became the first drug available to treat systemic sclerosis-associated ILD when the FDA approved the tyrosine kinase inhibitor in September 2019. Genentech’s subcutaneous injection Actemra (tocilizumab) followed as the first biologic with FDA approval in March 2021. See Also: Contentious Medicare price negotiations underway as US drug prices rise Inmagene to secure licence for two HUTCHMED drug candidates The market for systemic sclerosis is expected to be worth $2.05bn in 2030, as per GlobalData’s Pharma Intelligence Centre. GlobalData is the parent company of Pharmaceutical Technology . AnaMar says that there are no treatments on the market that stop or reverse scarring in both lung and skin tissue. The biotech says its candidate has a dual-action approach to treat both these aspects of the disease. AM1476 has established pharmacokinetic and safety profiles based on Phase I data. An already-designed Phase II trial will evaluate the treatment effects of AM1476 in 60 patients with systemic sclerosis-associated ILD. Patients’ lung function and skin thickness will be assessed over a year. Australian biotech Certa Therapeutics gained FDA orphan drug designation for its systemic sclerosis candidate. Certa’s FT011 is also an oral anti-fibrotic agent. The company has already unveiled positive results from a Phase II trial assessing patients’ skin, with pivotal trial plans underway. GSK is also targeting scleroderma treatment with its B-cell inhibiting monoclonal antibody Benlysta (belimumab). Its candidate received an FDA orphan drug designation in February 2023. Though the company said it planned to initiate a Phase II/III trial in the first half of 2023, no updates have been issued since.