First-in-class, peripheral serotonin (5-HT2B) receptor antagonist being developed as a highly selective, oral, anti-fibrotic medicine for skin and lung disorders

LUND, Sweden I May 23, 2023 I AnaMar, a clinical-stage biotech company developing a first-in-class, peripheral 5-HT2B receptor antagonist, AM1476, as a pan anti-fibrotic medicine, announces positive results from its Phase I study, and the completion of Phase II enabling pre-clinical studies for its initial orphan indication in systemic sclerosis (SSc) characterized by lung and skin fibrosis.

AM1476, a highly selective small molecule, delivered as an orally administered tablet, was found to be safe and well-tolerated at all relevant doses in a trial of approximately 100 healthy subjects.

Skin fibrosis is a leading feature of SSc associated with significant disability. The degree of skin fibrosis provides insight about progression of the disease. Interstitial lung disease (ILD) is a group of conditions that cause progressive lung scaring, known as fibrosis, which lead to increasing, chronic, breathing problems and organ dysfunction, and eventually possibly death. There are currently no treatments on the market that effectively reverse scarring. AM1476 has been found to ameliorate key fibrotic pathways in vivo and ex vivo with the potential to halt and reverse scarring with potential utility across fibrotic disease.

A Phase II study has been designed 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 (forced vital capacity) and skin thickness (modified Rodnan skin score) as primary efficacy readouts. Active product ingredients are being made ready as cGMP materials for this Phase II trial. The company is planning regulatory submissions, in 2023, to the FDA and EMA for Orphan Drug Designation for the rare disease SSc. 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.

AnaMar’s CEO Dr. Ulf Ljungberg said: “Our Phase II ready compound AM1476 for the treatment of the orphan disease systemic sclerosis will be a significant milestone in the development of novel medicines to prevent, heal and slow organ scarring from fibrotic diseases. We hold a broad, patent-protected, portfolio of selective and high affinity 5-HT2B receptor antagonists. We have seen great potential from our pre-clinical and phase I studies, and now look forward to working with a pharma partner to turn our research into life-changing treatments for patients with fibrosis.”

AnaMar’s Head of Research, Dr. Christina Wenglén, said: “ILD and skin fibrosis are commonly seen complications of systemic sclerosis which are often progressive and have a poor prognosis. Which is why we see such 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. We are committed to progressing our novel therapeutics into clinical practice to address this pressing unmet medical need.”

In several well-known preclinical state-of-the-art animal models of fibrosis AM1476 halted and reversed the progression of pre-established fibrosis in skin and lung tissue, clearly demonstrating the anti-fibrotic efficacy of AM1476.

About AnaMar

Based in Lund, Sweden, AnaMar is developing a first-in-class, anti-fibrotic medicine to prevent, slow and heal scarring caused by fibrosis 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, which affect millions of patients but have limited, if any, treatment options, including systemic fibrotic disorders and organ-specific fibrotic disorders such as interstitial lung diseases. AM1476 performed successfully in in vitro and in vivo models of fibrosis, as well as demonstrating favourable safety and pharmacokinetic profiles in Phase I clinical studies. It 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 ensuring the best outcomes for those with fibrosis.

We are currently seeking collaborations with pharma for the advancement of AM1476 into Phase II clinical trials. In addition, available to prospective collaborators is our selective library of comprehensively profiled compounds. We have significant IP, all of which has been generated in-house.

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.