Magenta Therapeutics said Wednesday that it has received an FDA clinical hold letter regarding the investigational new drug application it filed in June to start a Phase I/II trial of MGTA-117 in patients with acute myeloid leukaemia (AML) and myelodysplastic syndrome (MDS). Company shares dipped about 9% lower on the news.

The anti-CD 117 amanitin antibody drug conjugate is designed to selectively deplete haematopoietic stem cells (HSCs) from patients prior to transplant or HSC-based gene therapy. The goal is to reduce the need for high-dose or high-intensity chemotherapeutic agents or, in the case of gene therapy applications, possibly eliminate the need for them altogether.

Agency asks for additional bioassay

According to Magenta, the FDA wants it to develop an additional bioassay "to be used in conjunction with the PK/PD (pharmacokinetics/ pharmacodynamics) model to inform dose escalation decisions in addition to safety monitoring." The company has started developing the bioassay and says it plans to work with the FDA to determine how it will be applied for dose escalation. Magenta noted this is the only clinical hold item identified by the agency, and is not related to either the toxicology or manufacturing of MGTA-117.

CEO Jason Gardner said the company does not see any significant technical challenges in completing the bioassay, and if the issue is resolved, it expects to open the study in the fourth quarter. "We are greatly appreciative of the FDA's continued engagement as we seek to…develop this potentially first-in-class medicine to improve conditioning options for patients across a number of disease areas," Gardner added.

The Phase I/II trial will assess MGTA-117 as a single agent in the relapsed/refractory AML and MDS patient population. Magenta said it anticipates transitioning the study to transplant-eligible patients once adequate safety and PK/PD data have been collected. It also plans to develop MGTA-117 as a targeted conditioning agent for patients with genetic diseases prior to delivery of ex vivo gene therapies.