New Study Demonstrates Integrin Activation Can Bring the Heat to Cold Melanoma Tumors
Houston, TX, May 20, 2022 – Together with The University of Texas MD Anderson Cancer Center (“MD Anderson”) and Texas Heart Institute (“THI”), 7 Hills Pharma LLC (“7 Hills” or “7HP”) released a new study in The Journal of Clinical Investigation, describing the use of 7HP’s novel integrin activator 7HP349 to convert “cold” or non-immunogenic tumor microenvironments to a “hot,” T cell-enriched state, improving the effectiveness of immune checkpoint blockade. The article, entitled “LFA-1 activation enriches tumor-specific CD8+ T cells in a cold tumor model and synergizes with CTLA-4 blockade,” was published by a team at MD Anderson led by Yared Hailemichael, Ph.D., assistant professor of Melanoma Medical Oncology, with co-authors from the 7-Hills and THI investigators.
7HP349 is a member of a family of small-molecule integrin activators discovered at the Texas Heart Institute in the laboratories of Dr. Peter Vanderslice, Dr. Ronald J. Biediger, and Dr. Darren G. Woodside. The family of compounds was generated using a rational design approach based on their deep understanding of and the relationship between the biology and three-dimensional structure of integrins.
“This landmark publication is the result of years of forward-looking thinking, innovative chemistry, and keen scientific investigation amongst our multidisciplinary teams and with our interinstitutional partners across the Texas Medical Center,” said Dr. Vanderslice. “Our goal is to bring more effective, less toxic immunotherapy treatments to cancer patients, and we are proud to see our unique approach to immune augmentation validated with this publication.”
7HP partnered with THI in 2014 to commercially develop the technology and soon teamed up with Hailemichael to elucidate the biology underlying these first-in-concept integrin activators.
“Our findings shed light on a new approach to improving cancer immunotherapy,” Hailemichael said. “We are excited to help move this therapeutic a step closer to additional clinical studies.”
7HP has garnered both FDA Fast Track and Orphan Drug designations for 7HP349 in advanced melanoma, highlighting the significant unmet needs of these patients. 7HP also recently completed a Phase I clinical trial on 7HP349, funded by the National Institutes of Health, demonstrating oral bioavailability and a clean safety profile. “We are grateful for the support of the National Cancer Institute’s SBIR program that has funded this work from pre-clinical validation and IND-enabling studies through completion of Phase I clinical testing,” said Upendra Marathi, CEO of 7HP. “Without their support, both financial and non-financial, our novel approach to reversing resistance to immune checkpoint inhibition could not have been possible.”
Hickman, A., Koetsier, J., Kurtanich, T., Nielsen, M. C., Winn, G., Wang, Y., Bentebibel, S.-E., Shi, L., Punt, S., Williams, L., Haymaker, C., Chesson, C. B., Fa’ak, F., Dominguez, A., Jones, R., Kuiatse, I., Caivano, A. R., Khounlo, S., Warier, N. D., … Hailemichael, Y. (2022). LFA-1 activation enriches tumor-specific T cells in a cold tumor model and synergizes with CTLA-4 blockade. Journal of Clinical Investigation. 2022. https://doi.org/10.1172/JCI154152.
Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under Award Number R42CA203456. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
About Texas Heart Institute
The Texas Heart Institute (THI), founded by world-renowned cardiovascular surgeon Dr. Denton A. Cooley in 1962, is a nonprofit organization dedicated to delivering the future of cardiovascular health through exceptional patient care, discovery, and commitment to learning. THI’s scientists and physicians are spearheading some of the most innovative research in the medical field through its translational basic and clinical research programs in cardiology, cardiovascular surgery, stem cell, and gene therapy, and regenerative medicine. As a global leader of patient care for nearly six decades, Texas Heart Institute has been ranked among the top cardiovascular centers in the United States by U.S. News & World Report for the past 30 years. With initiatives ranging from postdoctoral and continued medical education to public outreach and scientific publications, THI is dedicated to spreading awareness and sharing updates on ways to prevent, treat and defeat the cardiovascular disease. With over 10 million visitors coming to its website from around the world every year, www.texasheart.org is just one of the ways THI is helping to educate people on the importance of heart health. For more information, please visit texasheart.org
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About 7 Hills Pharma LLC
7 Hills Pharma is a clinical-stage immunotherapy company developing a platform of novel, oral small molecules for the treatment of cancer and prevention of infectious diseases. Our compounds are first-in-concept allosteric integrin activators that leverage a unique mechanism of action to stabilize the cell-cell interactions required to mount an effective immune response. Our lead clinical candidate, 7HP349, is the only reported systemically safe immune stimulant that can activate both cellular and humoral immunity. For more information, visit 7hillspharma.com
7HP349 is 7HP’s lead, clinical-stage integrin agonist. It is a first-in-class, orally delivered small molecule that safely and selectively activates the integrins LFA-1 and VLA-4 to augment the antigen-specific immune response. In preclinical models, 7HP349 has been shown to improve the effectiveness of a broad range of immune checkpoint inhibitors and a wide variety of infectious disease vaccines. In a Phase I clinical trial, 7HP349 demonstrated oral bioavailability and a clean safety profile at exposures well exceeding therapeutic levels.