New research to a study small molecule cell adhesion activator to facilitate the engraftment rate of cord blood cells
Credit: Photo Credit © 2020 Texas Heart Institute
The Texas Heart Institute and 7 Hills Pharma (7 Hills) received a $1.9 million, Phase II STTR (R42) grant from the National Heart Lung Blood Institute to advance further their lead product 7HP349, a novel integrin activator, to define the optimal dosing schedule for cord blood transplant along with a focus on development and production of a formulation that meets safety standards for filing an IND application with the FDA.
“The growing use of umbilical cord blood cells for bone marrow transplantation has allowed patients to receive treatment that otherwise could not find a suitable donor. Finding a means to improve the rate of immune reconstitution is critical to fully realize the potential of cord blood transplant and expanding its use to adult patients, ” Emerson Perin, MD, Ph.D., Texas Heart Institute Medical Director
Hematopoietic stem cell transplantation has become a preferred treatment for hematological malignancies and certain genetic disorders. Umbilical cord blood is an appealing alternative to bone marrow or peripheral blood as a source of hematopoietic stem cells for transplant. Unfortunately, there are fewer stem cells in these preparations, which results in delayed rates of immunological reconstitution.
“This is an adhesion problem,” according to Darren Woodside, Ph.D., Texas Heart Institute Vice President for Research and co-founder of 7 Hills. “Our studies will use a small molecule cell adhesion activator to facilitate the engraftment rate of cord blood cells and thus decrease the time to immune reconstitution.”
The work builds on proof-of-concept, Phase I STTR studies conducted at THI and 7 Hills evaluating the engraftment of human CD34+ cord blood cells into immunocompromised mice following administration of 7HP349.
“We have developed a unique small molecule that can activate integrins on cord blood cells, facilitating their interaction with their counter-receptors in the bone marrow. Compounds in this class can enhance all phases of the adhesion cascade including cell rolling, firm adhesion, and migration. This compound can be dosed independently of the cells and is inexpensive to synthesize on a large-scale. This would have an advantage over other technologies as no preconditioning or manipulations of the cells would be required meaning a more affordable and universally translatable therapy” according to Peter Vanderslice, Ph.D., Director of Biology in the Texas Heart Institute Molecular Cardiology Research and Co-founder of 7 Hills.
The team will now refine the dosing schedule and preclinical formulation and conduct toxicity studies required to file an Investigational New Drug application with the Food and Drug Administration.
The prestigious funding award will enable 7 Hills to make cGMP 7HP349 drug product and drug substance and continue to evaluate the utility of 7HP349 to augment stem cell transplants.
“We are honored to be recognized by the National Heart, Lung and Blood Institute of the NIH and pleased to continue our immuno-oncology drug development with the Texas Heart Institute and the other preeminent, industry thought-leaders,” said Upendra Marathi, Ph.D., President, and Chief Executive Officer of 7 Hills.
The new project was funded by the National Heart, Lung and Blood Institute (R42 HL129612-02) and is titled “A small molecule integrin activator to enhance cord blood transplant,” and the National Institute Of Allergy And Infectious Diseases of the National Institutes of Health under Award Number R41AI145507″ Integrin Activation as a Treatment for Leukocyte Adhesion Deficiencies “.The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.