On April 4, 2017 Bellicum Pharmaceuticals, Inc. (Nasdaq:BLCM), a leader in developing novel, controllable cellular immunotherapies for cancers and orphan inherited blood disorders, reported two presentations of preclinical results on the Company’s proprietary dual-switch technology for use in CAR-T and TCR product candidates at the 2017 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in Washington, D.C (Press release, Bellicum Pharmaceuticals, APR 4, 2017, View Source [SID1234518465]).

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"We’re excited to report compelling preclinical data on the first dual-switch technology designed to provide control over both the activity and safety of cell-based therapies," said Rick Fair, Chief Executive Officer of Bellicum Pharmaceuticals. "These data in both CAR-T and TCR constructs support our objective to continue leading the industry in developing novel, controllable cell therapies. We look forward to advancing product candidates incorporating this dual-switch technology into the clinic."

The Company’s dual molecular switch is designed to increase efficacy, durability and safety of adoptive cell therapies. T-cell proliferation is triggered by an inducible MyD88/CD40 (iMC) costimulatory switch, which when activated by the presence of both a target antigen and rimiducid, leads to enhanced T-cell activation and survival. A novel suicide switch, called RapaCIDeTM, is also engineered into the cell for use in the event of severe toxicities. RapaCIDe is activated via infusion of rapamycin, triggering immediate apoptosis of the modified cells. The dual-switch technology has been incorporated into the Company’s GoCAR-T and GoTCR platforms.

In a late-breaking poster presentation titled "Dual-switch HER2 CAR-T cells: Small molecule-regulated GO and STOP switches to target solid cancer in vivo," Bellicum scientists tested the novel dual-switch platform in solid tumors by combining both the iMC costimulatory and RapaCIDe apoptotic signaling switches inside a first-generation CAR targeting HER2. Results showed that the novel RapaCIDe switch was as effective as the Company’s CaspaCIDe switch at activating apoptosis, while the iMC costimulatory switch enhanced tumor killing and T-cell proliferation. This study demonstrated that the Company’s dual-switch GoCAR-T technology effectively controlled tumor growth, T-cell proliferation/persistence and elimination in a solid tumor model.

Additional data were reported in a second presentation on the Company’s dual-switch technology in a TCR targeting the cancer antigen PRAME (preferentially expressed antigen in melanoma). The TCR was engineered with the rimiducid-driven iMC costimulatory switch and the RapaCIDe suicide switch. Results reported in a poster presentation titled "Dual-switch TCR: A two-ligand system to control PRAME TCR-modified T-cell proliferation and death using inducible MyD88/CD40 and caspase-9," showed that T cells transduced with the dual-switch technology effectively enhanced T-cell proliferation/persistence in the presence of rimiducid, and exposure to rapamycin effectively triggered the RapaCIDe switch and induced apoptosis, eliminating the cells. This is the first reported prototype of a dual-switch TCR designed to increase efficacy, durability and safety of adoptive T-cell therapies.

The posters will be available in the Abstracts & Presentations section of the Bellicum website after the presentations.

AACR Presentation Details

Late-Breaking Presentation:

Abstract Number: LB-184 / 7
Presentation Title: "Dual-switch HER2 CAR-T cells: Small molecule-regulated GO and STOP switches to target solid cancer in vivo"
Presentation Date: Tuesday, April 4, 2017
Presentation Time: 8:00 AM – 12:00 PM ET
Section: 35
Additional Presentation:

Abstract Number: 3745 / 1
Presentation Title: "Dual-switch TCR: A two-ligand system to control PRAME TCR-modified T cell proliferation and death using inducible MyD88/CD40 and caspase-9"
Presentation Date: Tuesday, April 4, 2017
Presentation Time: 8:00 AM – 12:00 PM ET
Section: 30