Magenta Therapeutics Inc. has closed a $52 million series C financing that it said will be used to advance its portfolio of bone marrow transplantation therapies. The Cambridge, Mass.-based company is testing its most advanced candidate, MGTA-456, in a phase II trial for patients with inherited metabolic diseases.

The oversubscribed round was led by Casdin Capital, with participation from new investors Ecor1 Capital, Eventide Asset Management, Watermill Asset Management and additional institutional investors. Existing investors Be the Match Biotherapies and Access Industries also participated.

The company's earlier financings included a $48.5 million series A round in November 2016, which followed its incubation by co-investors Third Rock Ventures LLC and Atlas Venture, and a $50 million series B in May 2017. (See BioWorld Today, Nov. 17, 2016.)

Bone marrow transplants can save the lives of people with blood cancers, genetic and severe autoimmune diseases, but it remains risky, with toxic side effects and complexity for patients that could benefit from the procedure, according to the company. Magenta's team is working to address those challenges by developing an integrated portfolio of therapeutics, the most advanced of which is MGTA-456.

Magenta in-licensed the candidate, formerly known as HSC-835, from Basel, Switzerland-based Novartis AG to support the use of stem cell transplantation in a variety of disease settings, including immune and blood diseases. It comprises a single allogeneic umbilical cord blood unit expanded ex vivo with LFU-835, a small-molecule aryl hydrocarbon receptor (AHR) antagonist. It's administered through bone marrow transplantation.

Following a 36-patient proof-of-concept study in several blood cancers, on April 5 the company treated the first patient with an inherited metabolic disorder in its phase II study. That trial, currently enrolling at the University of Minnesota, is designed to enroll 12 patients with Hurler's syndrome, adrenoleukodystrophy, metachromatic leukodystrophy or globoid cell leukodystrophy. The primary endpoint is engraftment after transplantation. The secondary endpoint is transplant-related safety and tolerability.

"AHR antagonism is a novel, well-studied and clinically validated pathway that controls cell self-renewal and differentiation," the company said. By leveraging that pathway, the company hopes that MGTA-456 might allow patients to "be treated with higher cell doses than would otherwise be possible, and to have access to better HLA-matched cord blood units, both of which have been shown to provide better outcomes and lower rates of post-transplant complications," it said.

No other companies are known to be working on AHR antagonism specifically for hematopoietic stem cell transplantation, though both Cambridge, Mass.-based Kyn Therapeutics Inc. and Hercules Pharmaceuticals BV have explored compounds of the class for the potential treatment of cancer, according to Cortellis Competitive Intelligence.

Magenta is also working to improve both the process and outcomes of bone marrow transplant through research on transplant conditioning and stem cell mobilization programs. At the American Society of Hematology (ASH), it showcased preclinical data on GRO-beta, also known as MGTA-M100, a CXCR2 agonist used in combination with the established mobilization agent plerixafor (Sanofi SA).

In studies of nonhuman primates presented at ASH, Magenta reported that a single administration of GRO-beta in combination with plerixafor induces robust mobilization of a transplantable dose of CD34+CD90+CD45RA-hematopoietic stem and progenitor cells within four hours of administration. By comparison, the current mobilization standard of care, G-CSF, requires a minimum of five days of treatment, multiple outpatient visits, and is often associated with bone pain, nausea, headache and fatigue, the company said.

The company has also been active in developing a new collaboration with Ladenburg, Germany-based Heidelberg Pharma AG. In March, the companies signed an exclusive multitarget research agreement covering the combination of Magenta's stem cell platform with proprietary antibodies across up to four exclusive targets with Heidelberg Pharma's amanitin toxin-linker platform technology.

The agreement, which included up-front technology access, exclusivity and research support payments of undisclosed value, also gives Magenta an option for an exclusive target-specific license for each of the product candidates resulting from the pair's work. Heidelberg would be eligible to receive option fees, clinical development, regulatory and sales-related milestone payments up to $334 million if Magenta exercises all target options and all milestones are met.

Neither the company nor Casdin responded to requests for comment.