P53MVA has wide therapeutic implications and is currently being studied in 2 clinical trials; one is a combination with gemcitabine in refractory ovarian cancerand the other is a combination with pembrolizumab for multiple cancers. shIDO-ST targets the immunosuppressive molecule indoleamine 2,3-dioxygenase (IDO) and in combination with an enzyme, PEGPH20, successfully combats pancreatic tumors.
NEW YORK & DUARTE, Calif.--(BUSINESS WIRE)-- Tara Immuno-Oncology LLC (Tara I-O, Private, with offices in NY and CA) announced today the acquisition of licenses from City of Hope for the development of p53MVA (modified vaccinia ankara) and a Salmonella-based therapy targeting Indoleamine 2,3-Dioxygenase (shIDO-ST), both for multiple oncology indications. Both technologies originate from the pioneering work of Don J. Diamond, Ph.D., chair of the Department of Experimental Therapeutics at City of Hope, an independent biomedical research institution and cancer treatment center. Tara I-O will pay City of Hope upfront and milestone payments in excess of $10 million, in addition to commercial royalties for the exclusive licenses.
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"Our mission at Tara Immuno-Oncology is to utilize novel therapies to harness the body's immune system to treat and potentially cure cancer patients," said Dhesh S. Govender, founder and CEO of Tara Immuno-Oncology. "We recognized the thoughtful approach and hard work of Don Diamond and his team of scientists to advance both p53MVA and shIDO-ST as novel immuno-oncology assets. We are very encouraged by the compelling data and responses from patients thus far and look forward to working with City of Hope to rapidly advance both therapies."
George Megaw, Director of the Office of Technology Licensing at City of Hope, added: "City of Hope believes Tara I-O's development expertise uniquely positions it to advance both the p53MVA and the shIDO-ST technology, ultimately providing more effective treatments for cancer patients here and around the world."
TP53 mutations are present in the majority of solid tumors, resulting in the accumulation of mutant p53 protein. In contrast, the concentration of normal p53 in healthy cells is low, making p53 an attractive cancer target with potentially wide therapeutic applications.
A Phase 1 trial in patients with refractory gastrointestinal malignancies was completed in 2014 and published. p53MVA immunization was well-tolerated at both doses, with no adverse events above grade 2. CD4+ and CD8+ T cells showing enhanced recognition of a p53 overlapping peptide library were detectable after the first immunization, particularly in the CD8+ T-cell compartment (P=0.03). The frequency of PD1+ T cells detectable in patients' peripheral blood mononuclear cells (PBMC) was significantly higher than in healthy controls.
Furthermore, the frequency of PD1+ CD8+ T cells showed an inverse correlation with the peak CD8+ p53 response (P=0.02) and antibody blockade of PD1 in vitro increased the p53 immune responses detected after the second or third immunizations. Induction of strong T-cell and antibody responses to the MVA backbone were also apparent.
There are 2 ongoing clinical trials: one in combination with PD-1 blockade antibody in multiple indications (NCT02432963) and another in combination with gemcitabine for refractory ovarian patients (NCT02275039).
Bacterial-based therapies are emerging as effective cancer treatments and hold promise for refractory neoplasms such as pancreatic ductal adenocarcinoma (PDAC), which has not shown significant improvement in therapy for more than 25 years. ShIDO-ST uses a modified Salmonella-based bacterium to target the immunosuppressive molecule indoleamine 2,3-dioxygenase (IDO), which camouflages cancer cells and prevents the immune system from recognizing and killing the tumor. The modified bacterium, dubbed shIDO-ST, is combined with the enzyme PEGPH20, which depletes extracellular matrix hyaluronan. This combination has been shown in preclinical studies to extend survival with frequent total regression of autochthonous and orthotopic PDAC tumors (published).
This observation was associated with migration and accumulation of activated polymorphonuclear neutrophils (PMN) from spleens into tumors, which was not seen in controls. Purified splenic PMNs from PEGPH20/shIDO-ST-treated mice exhibited significant IDO knockdown and were able to kill tumor targets ex vivo through mechanisms involving FasL and serine proteases.
In addition, CD8(+) T cells were observed to contribute to late control of pancreatic tumors. Data thus far demonstrate that entry of shIDO-ST and PMNs into otherwise impermeable desmoplastic tumors highlights an important component of effective treatment for pancreatic tumors.
Clinical trials are expected in 18-24 months.
About Tara Immuno-Oncology LLC:
Tara I-O is a private biopharmaceutical company formed in 2014 to advance novel immuno-oncology assets. Tara I-O has offices in New York, NY, and San Diego, CA. The company is utilizing its biotechnology drug development and business expertise to advance therapies toward registration and commercialization. Management has over 25 years of development experience with a proven track record of drug approvals.
About City of Hope
City of Hope is an independent research and treatment center for cancer, diabetes and other life-threatening diseases. Designated as a comprehensive cancer center, the highest recognition bestowed by the National Cancer Institute, City of Hope is also a founding member of the National Comprehensive Cancer Network, with research and treatment protocols that advance care throughout the nation. City of Hope's main hospital is located in Duarte, California, just northeast of Los Angeles, with community clinics throughout southern California. It is ranked as one of "America's Best Hospitals" in cancer by U.S. News & World Report. Founded in 1913, City of Hope is a pioneer in the fields of bone marrow transplantation and genetics.
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View source version on businesswire.com: http://www.businesswire.com/news/home/20151103005563/en/
Source: City of Hope
To read more Press Release articles, click here.