Japanese agency awards $32M to advance sickle cell treatment to trials
Goal is to show proof-of-concept for EPF-001 for treating blood diseases
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The Japan Agency for Medical Research and Development (AMED) — a national funding agency created to support medical R&D in the Asian nation — has awarded up to $32 million to Epifrontier Therapeutics to advance the clinical development of EPF-001, its investigational therapy for sickle cell disease (SCD) and beta thalassemia, two blood disorders.
The funding will support EPF-001’s advancement through Phase 2 clinical trials to assess the treatment’s safety and effectiveness, according to a company press release announcing the award. Trials are planned to start in medical institutions with large patient populations in other countries, with Japan mainly enrolling participants with severe beta thalassemia.
“This AMED grant recognizes the potential of the underlying science and provides crucial support as we advance EPF-001 toward clinical proof-of-concept,” said Bruce Goldsmith, PhD, Epifrontier’s CEO. “We are committed to realizing the therapeutic promise of this molecule for patients worldwide.”
The developer noted that “current treatment options [for these conditions] remain limited, and many patients continue to experience severe complications and reduced quality of life.”
Similar to beta thalassemia, SCD is caused by mutations in the beta-globin (HBB) gene, which affects the production of hemoglobin, the oxygen-carrying protein in red blood cells.
In SCD, the production of a faulty hemoglobin version causes red blood cells to assume a sickle-like shape, making them more prone to destruction and to stick together and obstruct blood vessels. In beta thalassemia, low levels of hemoglobin are produced, resulting in low levels of healthy red blood cells, or anemia.
Increasing fetal hemoglobin (HbF) — a version made before birth that carries oxygen more efficiently than adult hemoglobin — is a validated strategy for preventing cell sickling in SCD and compensating for low hemoglobin levels in beta thalassemia. Hydroxyurea, a standard SCD treatment, was previously shown to increase HbF levels.
EBF-001 designed to increase fetal hemoglobin levels in patients
EPF-001, also known as RK-701, is an oral therapy that works by selectively suppressing G9a, an enzyme that blocks the activity of certain genes, including those that encode a subunit of HbF. Thus, use of the therapy is expected to increase HbF levels.
The treatment candidate was developed under a research collaboration between the Riken Program for Drug Discovery and Medical Technology Platforms and the Tokyo University of Pharmacy and Life Sciences.
“We are honored to build upon the groundbreaking research conducted by our scientific founders at Riken and Tokyo University,” Goldsmith said. “Their innovative approach to targeting G9a has yielded a clinical candidate with the potential to meaningfully improve outcomes for patients suffering from beta globin disorders.”
EPF-001 was identified through a comprehensive screening of about 140,000 compounds, per the developer. Further testing of more than 1,000 molecules pointed to EPF-001 as a highly specific G9a blocker.
In preclinical studies, it was shown to induce HbF production more efficiently and with lower toxicity than hydroxyurea in human cells and mice, according to the company.
The pioneering work by Riken and Tokyo University of Pharmacy and Life Sciences has created a truly differentiated clinical candidate with the potential to transform treatment for patients with beta globin disorders.
Minoru Yoshida, PhD, Riken’s executive vice president, said EPF-001’s development “exemplifies Riken’s commitment to translating fundamental scientific discoveries into therapies that address critical unmet medical needs through … collaborative efforts.”
He added: “We are pleased to see this research transition from Riken to EpiFrontier Therapeutics for clinical development, and we are grateful for AMED’s continued support of this project.”
Epifrontier was founded last year as a U.S.-based corporation with a Japanese subsidiary (Epifrontier Therapeutics), with support from The University of Tokyo Edge Capital Partners (UTEC).
Building on an exclusive license from Riken and Tokyo University of Pharmacy and Life Sciences, the company is pursuing additional patent filings for formulation, dosage, administration methods, and potential combination therapies.
“The pioneering work by Riken and Tokyo University of Pharmacy and Life Sciences has created a truly differentiated clinical candidate with the potential to transform treatment for patients with beta globin disorders,” said Azusa Shiohara, principal at UTEC and board member of Epifrontier. “We are proud to support this company as it brings this important Japanese innovation to patients worldwide, and we are grateful for AMED’s significant investment in validating and advancing this breakthrough therapy.”
