Unlocking the potential of hematopoietic stem cell transplantation
CEO: Jason Gardner
Based: Cambridge, Massachusetts
Clinical focus: Autoimmune and genetic diseases
The scoop: Hematopoietic stem cell transplantation (HSCT) has transformed the treatment of some diseases, but its use remains fraught with risk; in fact, it can either be lifesaving or life-ending, according to Magenta Therapeutics CEO Jason Gardner, Ph.D., and that means it is generally limited to use in a handful of conditions such as blood cancers.
The company has the "big vision" of improving HSCT so that it can be used "in many more patients and across many more types of diseases," including autoimmune conditions like multiple sclerosis, Crohn's disease or type 1 diabetes, Gardner says.
What makes Magenta Fierce: The approach taken by Magenta is to advance on all fronts in HSCT, bringing forward multiple drug programs that tackle a particular area of transplant medicine that could be improved upon. In a nutshell, that boils down to the tolerability of the treatment patients undergo when they are prepared for transplant and the challenge of harvesting and delivering sufficient stem cells—from bone marrow, peripheral blood or umbilical cord blood—to ensure a successful graft.
"We're still putting patients through a procedure that hasn't fundamentally changed for the last 50 years," says Gardner. "Despite the curative potential, safety issues have relegated transplant to the last line of treatment for many patients."
Magenta has been set up with its own platform of antibody-drug conjugate (ADC) candidates designed for conditioning, the necessary removal of a patient's own stem cells to make way for the new ones. The intention is to develop more targeted and less toxic alternatives to high-dose chemoradiation, a sledgehammer approach that is still used despite the risk of terrible side effects such as nausea, vomiting, diarrhea, bleeding, infection, and death. Those ADC candidates are still in preclinical development but could be in the clinic within the next couple of years.
Another area of in-house research for the company is mobilization—moving stem cells from the bone marrow to the blood—and Magenta says it has a couple of preclinical programs that are trying to achieve that more effectively and rapidly than current therapies such as granulocyte-colony stimulating factor (G-CSF). Growth factors like G-CSF need to be delivered over several days and can also cause side effects, particularly in patients with autoimmune disease, and Magenta thinks its chemokine program could be more potent, act in as little as 30 minutes and sidestep those issues.
Finally, Magenta has a clinical-stage candidate—licensed from Chief Scientific Officer Mike Cooke's former employer Novartis—that could offer a means of expanding the number of stem cells outside the body and thereby increasing the dose of cells that can be delivered during a transplant, hastening immune recovery and improving the chances of a good donor match. Gardner notes that this has been a long-term goal in HSCT as clinical outcomes are directly correlated with stem cell numbers transplanted, and many patients receive transplants with too few cells.
That candidate—a small molecule called MGTA-456 (formerly HSC835) that, when added to incubation media, increases stem cell numbers up to 400-fold—is set to start phase 2 testing later this year, with the potential to file for approval as soon as a couple of years later.
Magenta believes the company is unique in this multipronged approach to HSCT, with the potential of combining its therapies into a "toolbox" to help physicians and patients as they undergo a transplant. If all the elements come good, it could introduce a completely different way of practicing medicine for patients whose diseases stem from a malfunctioning immune system, according to Gardner, making curative, one-time HSCT a new way of handling diseases that currently require long-term, chronic treatment.
"We are looking forward to the future as we execute on our vision to reboot the conversation between patient and doctor and at the same time use HSCT to clinically reboot patients' immune systems to fight cancers, genetic diseases and autoimmunity," he says.
Investors: Atlas Ventures, Third Rock Ventures, Google Ventures, Casdin Capital, Partners Innovation Fund, Access Industries