On November 11, 2015 Immune Design (Nasdaq:IMDZ), a clinical-stage immunotherapy company focused on oncology, reported the start of a randomized Phase 2 trial of CMB305, the company’s "prime boost" cancer immunotherapy product candidate, combined with Genentech’s investigational cancer immunotherapy, atezolizumab (MPDL3280A; anti-PD-L1) in patients with soft tissue sarcoma (Press release, Immune Design, NOV 11, 2015, View Source [SID:1234508204]).

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The open label trial is designed to evaluate the safety and efficacy of CMB305 in combination with atezolizumab versus atezolizumab alone in up to 80 patients with locally advanced, relapsed, or metastatic synovial sarcoma or myxoid/round-cell liposarcoma expressing the NY-ESO-1 cancer testis antigen. The trial is being conducted pursuant to a clinical collaboration with Genentech, a member of the Roche Group, which will provide atezolizumab for the trial.

CMB305 is a "prime-boost" cancer immunotherapy product designed to synergistically induce and expand in vivo cytotoxic T lymphocytes (CTLs) targeting NY-ESO-1 which is found in a broad set of tumors. Specifically, synovial sarcoma and myxoid/round-cell liposarcoma tend to express NY-ESO-1 broadly, which should make them good indications for clinical studies of this antigen-specific immune therapy. Atezolizumab is designed to target PD-L1 expressed on tumor cells and tumor-infiltrating immune cells, preventing it from binding to PD-1 and B7.1 on the surface of T cells. By inhibiting PD-L1, atezolizumab may enable the activation of T cells..

"This trial provides our first opportunity to validate the fundamental hypothesis that combining cutting-edge technologies designed to trigger in vivo anti-tumor CTLs with antagonists of the PD-1/PD-L1 axis should be additive, if not synergistic, and thus could enhance the potential therapeutic benefit to patients," said Carlos Paya, M.D., Ph.D., President and Chief Executive Officer of Immune Design. "We are excited to work with leading sarcoma investigators to advance CMB305 into its first randomized Phase 2 trial and to explore the potential of these two approaches."

About CMB305

CMB305 is a cancer immunotherapy product candidate combining two potentially synergistic agents, LV305 and G305. LV305 is a hybrid vector from the ZVex discovery platform that specifically targets dendritic cells (DCs) in vivo and delivers the RNA for NY-ESO-1, enabling the DCs to express the entire tumor antigen and potentially induce a diverse set of CTLs targeting NY-ESO-1 in tumors. G305, in contrast, is designed to boost the CTL response via the induction of antigen-specific CD4 "helper" T cells. G305 consists of recombinant NY-ESO-1 protein formulated with a proprietary synthetic small molecule called glucopyranosyl lipid A (GLA), the novel TLR4 agonist at the core of the GLAAS platform. CMB305 is intended to be an "off-the shelf" therapy that does not require patient-specific manufacturing or ex vivo manipulation of patient samples. Having established the safety and individual immunologic activity of LV305 and G305 in prior studies, Immune Design initiated a new Phase 1B study of the product candidate CMB305 earlier this year.

About Soft Tissue Sarcoma

Soft Tissue Sarcomas (STS) are malignancies that arise from the soft tissues of the body, such as tissues that connect, support and surround other body structures including muscle, fat, blood vessels, nerves, tendons and the lining of joints.1 In the United States, nearly 12,000 people will be diagnosed and approximately 4,870 are expected to die of STS in 2015.2 There are approximately 50 different types of STS including Liposarcomas and Synovial Sarcomas, which are subtypes affecting fat tissue and tissue around the joints, respectively.3 Myxoid/round cell is a type of liposarcoma that accounts for approximately 30% of all liposarcoma cases.4 Myxoid and round cell liposarcoma and synovial sarcomas have been shown to have high expression of NY-ESO-1, approximately 90% and approximately 60%, respectively.5

On November 11, 2015 Five Prime Therapeutics, Inc. (Nasdaq:FPRX), a clinical-stage biotechnology company focused on discovering and developing novel protein therapeutics for cancer and inflammatory diseases, reported that the Federal Trade Commission has granted early termination of the waiting period under the Hart-Scott-Rodino Antitrust Improvement Acts of 1976 (HSR Act) in connection with the exclusive worldwide license and collaboration agreement with Bristol-Myers Squibb (BMS) for the development and commercialization of Five Prime’s colony stimulating factor 1 receptor (CSF1R) antibody program, including FPA008 (Press release, Five Prime Therapeutics, NOV 11, 2015, View Source [SID:1234508192]). With the early termination of the applicable waiting period under the HSR Act, the collaboration agreement with BMS is effective as of November 10, 2015, and the related $350 million upfront payment by BMS to Five Prime is due within 30 days of the effective date.

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Additional details regarding the collaboration can be found in Five Prime’s Form 8-K filed with the Securities and Exchange Commission on October 15, 2015.

About FPA008

FPA008 is an investigational antibody that inhibits CSF1R and has been shown in preclinical models to block the activation and survival of monocytes and macrophages. Inhibition of CSF1R in preclinical models of several cancers reduces the number of immunosuppressive tumor-associated macrophages (TAMs) in the tumor microenvironment, thereby facilitating an immune response against tumors. FPA008 is currently in phase 1 clinical trials in several immunology and oncology indications.