Magenta Therapeutics highlighted progress across its portfolio of targeted conditioning and stem cell mobilization programs and set out its milestone expectations for both clinical and preclinical data in 2022. MGTA-117 Program: 2022 Clinical Data from Phase 1/2 Clinical Trial: Evaluating Target Selectivity, Potency and Tolerability. The MGTA-117 Phase 1/2 clinical trial is open for enrollment.

This dose escalation clinical trial will evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of MGTA-117 as a single dose in patients with relapsed/refractory Acute Myeloid Leukemia (AML) and Myelodysplasia-Excess Blasts (MDS-EB). Specifically, dosing cohorts expected to enroll in 2022 will allow for evaluation of MGTA-117's ability to: selectively target CD117 as measured by receptor occupancy; potently deplete CD117-expressing cells such as stem cells, progenitors, and tumor cells; and rapidly clear from the body with a well-tolerated profile as determined by pharmacokinetic analysis and clinical chemistry tests, respectively. The company's preclinical evidence supports the MGTA-117 target selectivity, potency and tolerability profile.

In GLP toxicology studies, MGTA-117 potently depleted stem cells at a dose level where there were no drug-related findings in hepatic, reproductive, neurologic, cardiovascular, or respiratory organs. Phase 1/2 Clinical Trial Design for MGTA-117. MGTA-117 will be assessed in patients with relapsed/refractory AML and MDS-EB in a multi-center, open-label, single-ascending-dose trial.

Patients in the first cohort will receive 0.02 mg/kg administered intravenously (IV), and subsequent cohort doses will be determined in accordance with a modified Fibonacci sequence. The company will assess data from each cohort and, after collection of adequate safety, pharmacokinetic and pharmacodynamic data, Magenta intends to engage with the U.S. Food and Drug Administration (FDA) to transition to the primary target population of patients eligible for stem cell transplantation. In addition, Magenta plans to explore MGTA-117 as a targeted conditioning agent for stem cell gene therapies.

CD45-Antibody Drug Conjugate Program: The company has initiated investigational new drug application-enabling studies on its second targeted conditioning program, an antibody drug conjugate (ADC) targeting CD45. Due to the expression of CD45 on stem cells and immune cells, Magenta's CD45-ADC is designed to selectively target and deplete stem cells and lymphocytes, which could allow patients with blood cancers and autoimmune diseases to avoid use of chemotherapy prior to stem cell transplant. Magenta expects to have preclinical data from a dose ranging toxicology study in the second half of 2022.

Stem Cell Mobilization and Collection: MGTA-145 Dosing and Administration Optimization Clinical Trial. As previously disclosed, Magenta intends to initiate a dosing and administration optimization clinical trial with MGTA-145 in combination with plerixafor. Clinical data from a Phase 2 investigator-initiated clinical trial with 25 multiple myeloma patients showed that MGTA-145, in combination with plerixafor, mobilized a sufficient number of stem cells for transplantation in 88% of patients (22/25).

In addition, all patients transplanted with cells mobilized by MGTA-145 plus plerixafor as of the data cut-off date had successful engraftment (18/18 patients) with prolonged durability through the 100-day follow-up period (13/13 patients). The regimen was generally well-tolerated. Magenta believes there are specific opportunities to further improve cell collection yield by adjustments to the regimen dosing, and administration timing.

The company expects to generate data from this healthy subjects clinical trial in the second half of 2022. Sickle Cell Disease (SCD) – Stem Cell Mobilization Phase 2 Clinical Trial. Magenta is advancing trial initiation activities.

The trial is designed to evaluate mobilization and collection of stem cells in adults and adolescents with SCD. Magenta and its clinical collaboration partner, bluebird bio, will each characterize the collected cells. Magenta plans to gene-modify the cells and transplant them into established preclinical models to evaluate graft quality and engraftment.

Data from this clinical trial could provide proof-of-concept for MGTA-145, in combination with plerixafor, as a first-line mobilization regimen for patients with SCD and, more broadly, across other gene therapy applications. The company expects to generate data from this clinical trial in the second half of 2022.