New partners to develop universal gene therapy for hemophilia

ReciBioPharm, GeneVentiv to advance GENV-HEM to Phase 1/2 clinical testing

Margarida Maia, PhD avatar

by Margarida Maia, PhD |

ReciBioPharm and GeneVentiv Therapeutics are teaming up to advance the development of GENV-HEM, a gene therapy for all hemophilia patients, including those who have developed inhibitors against their missing clotting factors.

Developing a gene therapy requires efficient, flexible, and fast manufacturing, and each step must meet milestones to ensure success. ReciBioPharm will use its Massachusetts facility to help GeneVentiv take GENV-HEM from preclinical development to Phase 1/2 clinical testing.

“Gene therapies pose unique development and manufacturing challenges, so it was essential we chose the right partner to collaborate with, to minimise manufacturing risks and ensure we meet our key development milestones,” Damon Race, GeneVentiv’s CEO, said in a press release.

Hemophilia occurs when one of the clotting factors needed for the blood to clot properly is faulty or missing. As a result, patients are prone to prolonged and excessive bleeding, which can happen either spontaneously or following an injury or surgery.

Immune system sometimes sees provided clotting factor as threat

Factor replacement therapy can help prevent or stop bleeding by providing the faulty or missing clotting factor to hemophilia patients. However, the immune system sometimes sees the provided clotting factor as a threat and makes inhibitors (neutralizing antibodies) against it.

Inhibitors can render treatments less effective or even cause them to fail altogether. Patients who develop inhibitors often require other types of treatments, such as immune tolerance induction (attempt to reset the immune system to tolerate what it perceives as a threat) or bypassing agents to keep bleeding under control.

Given as a one-time infusion into the bloodstream, GENV-HEM is designed to deliver a gene coding for activated clotting factor V (FVa). The gene is carried aboard adeno-associated virus 8 (AAV8), which has been modified to not cause disease in humans.

FVa interacts with another protein in the clotting cascade, called factor X (FX), triggering steps to form a blood clot. This mechanism bypasses the need for factor VIII (FVIII) or factor IX (FIX), which are the clotting factors missing or being neutralized by inhibitors in patients with hemophilia A or B.

GENV-HEM prevented bleeding in animal models

In preclinical studies conducted in preparation for an investigational new drug application for first-in-human testing, GENV-HEM safely and effectively prevented bleeding in hemophilia animal models, regardless of the presence of inhibitors.

“We are delighted to be working with GeneVentiv, an ambitious and innovative biotech who wanted to leverage not just our equipment and space, but our extensive knowledge and expertise too,” said Xiaojun Liu, PhD, who directs ReciBioPharm’s AAV process development.

The company is expected to provide a gene therapy product that meets Good Manufacturing Practice standards for quality, as well as Good Laboratory Practice requirements for testing, recording, and storing data.

“ReciBioPharm quickly demonstrated that their team is the perfect development and manufacturing partner for our asset, enabling us to access their extensive experience and impressive capabilities,” Race said.

In November 2021, GENV-HEM was granted orphan drug designation by the U.S. Food and Drug Administration for hemophilia A and B, with or without inhibitors.