On March 2, 2020 Unum Therapeutics Inc. (NASDAQ: UMRX), a biopharmaceutical company focused on developing curative cell therapies for solid tumors, reported plans to prioritize resources towards advancing its preclinical program, BOXR1030, for the treatment of solid tumor cancers (Press release, Unum Therapeutics, MAR 2, 2020, View Source [SID1234555110]). Unum’s BOXR1030 expresses a glypican-3 (GPC3) targeted CAR and incorporates the novel transgene glutamic-oxaloacetic transaminase 2 (GOT2) to improve T cell function in the solid tumor microenvironment by enhancing T cell metabolism. Unum has initiated formal preclinical development activities, including preclinical safety testing and GMP process development, to support filing an IND application for BOXR1030 in late 2020.
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As part of this effort, and to conserve resources for BOXR1030, Unum is concluding its ACTR707 clinical trials, including the Phase 1 trial (ATTCK-20-03) in combination with rituximab in relapsed/refractory non-Hodgkin lymphoma and the Phase 1 trial (ATTCK-34-01) in combination with trastuzumab to treat advanced HER2+ solid tumor cancers. In addition, the company plans to reduce its current workforce by 43 employees (approximately 60 percent) to focus efforts on the BOXR1030 program. Unum also announced today that its Chief Scientific Officer, Seth Ettenberg, Ph.D., has resigned after five years of service to the company. Unum expects to continue to leverage its BOXR discovery platform, potentially in collaboration with partners, to create and develop new BOXR product candidates to address a broad range of solid tumor cancers.
"Following a detailed review of our operations, opportunities, and cash reserves, we believe the decisions announced today are in the best interests of all Unum stakeholders, including patients, clinicians, employees and shareholders," said Chuck Wilson, Ph.D., President and Chief Executive Officer of Unum Therapeutics. "We remain committed to addressing the challenges of treating solid tumor cancers, and would like to thank the patients, their families, and the investigators who have made our efforts to date possible. In addition, we would like to thank Seth for his contributions to the preclinical discovery efforts here at Unum over the years and wish him the very best in his next endeavor."
Unum will provide severance, continuation of employee benefits and outplacement assistance to employees affected by the restructuring. As of September 30, 2019, Unum had cash and cash equivalents of $45.9 million. After implementation of this restructuring, Unum’s expects its current cash and cash equivalents to fund the company into mid-2021. Further details on the financial implications of the restructuring will be included in the company’s full-year 2019 results expected later this month and with related filings with the Securities and Exchange Commission.
About Unum’s BOXR1030 and BOXR Platform
Unum’s BOXR1030 was discovered from its Bolt-on Chimeric (BOXR) platform that is designed to discover novel "bolt-on" transgenes to be co-expressed with CARs, a T-cell receptor, or ACTR, to help T cells survive longer and perform better in the solid tumor microenvironment. BOXR candidates consist of two main components: 1) a targeting receptor that directs the T cell to attack tumor cells, which may be a traditional CAR receptor, a T-cell receptor, or Unum’s ACTR receptor, and 2) a novel "bolt-on" transgene that improves the intrinsic function of the T cell. Once discovered, BOXR transgenes are designed to be incorporated into several different types of therapeutic T cells, including both ACTR T cells and CAR-T cells, to impart new functionality to T cells.
Unum’s first product candidate selected from the BOXR platform, BOXR1030, expresses GPC3+ targeted CAR and incorporates the bolt-on GOT2 transgene to improve T cell function in the solid tumor microenvironment (TME) by enhancing T cell metabolism. Preclinical data with BOXR1030 was presented at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting in November 2019. In preclinical studies, BOXR1030 T cells were resistant to suppressive TME-like conditions, showing improved T cell proliferation under both hypoxic and low glucose conditions compared with control GPC3+ CAR-T cells. In vivo, BOXR1030 demonstrated superior activity compared to the parental CAR-T with treated animals achieving complete tumor regressions. Tumor infiltrating lymphocytes isolated from the tumors of treated animals revealed that BOXR1030 cells were more resistant to dysfunction and had fewer markers of exhaustion as compared to the control CAR-T cells.