MWTX-003 Wins FDA Fast Track Designation for Polycythemia Vera

FDA

The FDA has granted fast track designation to the investigational, anti-TMPRSS6 monoclonal antibody, MWTX-003 (DISC-3405), for use in the treatment of patients with polycythemia vera, according to an announcement from Disc Medicine, Inc.¹

Patients with hematologic diseases such as polycythemia vera, myelodysplastic syndrome (MDS), and beta-thalassemia are known to develop high levels of iron, which leads to survival and quality-of-life complications.² MWTX-003 was designed to boost the production of hepcidin, which suppresses serum iron. Preclinical data in animal models of beta-thalassemia and polycythemia vera have confirmed this ability.

“We are delighted to have received fast track designation for MWTX-003, which highlights the unmet need for [patients with] polycythemia vera and the potential of MWTX-003 in a disease where there are few treatment options,” John Quisel, JD, PhD, president and chief executive officer of Disc Medicine, Inc., stated in a press release.1 “We believe MWTX-003 is uniquely positioned to address the needs of [patients with] polycythemia vera and are excited to initiate a phase 1 trial in the coming months.”

Preclinical studies have demonstrated strong pharmacodynamic effects that are reflective of TMPRSS6 inhibition.3 Specifically, a single administration of MWTX-003 led to an approximate 70% suppression of serum iron that lasted for 3 weeks. Moreover, in non-clinical GLP safety studies, the agent showcased a strong toxicity profile.

In a model of beta-thalassemia, treatment with MWTX-003 resulted in significant effects on disease hallmarks such as iron overload, ineffective erythropoiesis, and splenomegaly. The production of hepcidin was boosted up to 4-fold, serum and liver iron was reduced by approximately 60% to 65%, red blood cell production increased, and spleen weight decreased.

MWTX-003 was in-licensed from Mabwell Therapeutics, and in November 2022, the FDA accepted an investigational new drug application for the agent.¹ In January 2023, the clinical-stage biopharmaceutical company shared development plans for MWTX-003 which consisted of establishing phase 1 proof-of-mechanism; this was planned for initiation in the second half of 2023, and would examine hepcidin, iron, and other hematologic parameters.³

They also shared plans to advance the agent into point-of-care studies focused on polycythemia vera. In a phase 1b/2a proof-of-concept study, they hope to evaluate the safety and pharmacokinetic profile of MWTX-003 in patients with polycythemia vera. These data could provide clarity on the regulatory development path for the agent, according to Disc Medicine.

There is interest in examining the agent in additional POC studies spanning a range of indications, including hereditary hemochromatosis, beta-thalassemia, and MDS.

References

1. Disc Medicine receives FDA fast track designation for MWTX-003 for the treatment of polycythemia vera. News release. Disc Medicine, Inc. September 20, 2023. Accessed September 21, 2023. https://ir.discmedicine.com/news-releases/news-release-details/disc-medicine-receives-fda-fast-track-designation-mwtx-003
2. MWTX-003. Disc Medicine, Inc. website. Accessed September 21, 2023. https://www.discmedicine.com/our-pipeline/mat-2-inhibitor/
3. Novel anti-TMPRSS6 monoclonal antibody portfolio: exclusive in-licensing agreement with Mabwell Therapeutics. Disc Medicine, Inc. January 20, 2023. Accessed September 21, 2023. https://ir.discmedicine.com/static-files/549caf12-e7be-45ff-8667-86908e4e6bdd