CaspaCIDe


CaspaCIDe: Our CID Safety Switch Technology

CaspaCIDe® is our CID safety switch technology designated to eliminate cells in the event of toxicity. The CaspaCIDe switch consists of the CID-binding domain coupled to the signaling domain of caspase-9, an enzyme that is part of the apoptotic pathway. Infusion of rimiducid is designed to trigger activation of this domain of caspase-9 (iCasp9), which in turn leads to selective apoptosis of the CaspaCIDe-containing cells. Because CaspaCIDe is designed to be permanently incorporated into our cellular therapies, the safety switch has the potential to be available for use long after the initial therapy is delivered. This technology is applied to our lead clinical product candidate, BPX-501, an adjunct T-cell therapy after allogeneic hematopoietic stem cell transplantation, and to our TCR product candidate, BPX-701.

We believe that CaspaCIDe is the optimal cell therapy safety switch technology. In human trials, CaspaCIDe has demonstrated clinical efficacy in human patients beginning as soon as 30 minutes after administration of the activating drug, rimiducid.

The following diagram reflects the mechanism of action of our CaspaCIDe safety switch:

CaspaCIDe_v2

CaspaCIDe has been evaluated in both preclinical and clinical studies, with additional Phase 1/2 clinical trials ongoing and planned. In addition to using our CaspaCIDe technology for the substantial elimination of cellular therapy, like an “off” switch, we are studying partial elimination of a cellular therapy, like a “dimmer” switch, by delivering reduced doses of rimiducid. We observed the dose response to rimiducid by measuring the viability of BPX-501 cells in culture following the addition of increasing amounts of rimiducid to the culture medium, as well as by measuring the survival of BPX-501 cells in vivo in immune-deficient mice following injection of increasing doses of rimiducid. In these preclinical studies, rimiducid rapidly and consistently reduced or eliminated CaspaCIDe-containing cells in a dose-dependent manner.

 

In vitro and in vivo effect of rimiducid on killing of CaspaCIDe-containing T-cells. (Left) BPX-501 T cells made from six healthy donors were cultured for 24 hours with log-dilutions of rimiducid (0 – 10 nM). (Right) Five groups of three immune deficient mice were injected intravenously with 10 million human BPX-501 T cells followed by varying doses of rimiducid (0 – 5 mg/kg) 24 hours later. One day later, the spleens were isolated and analyzed for the presence of BPX-501 T cells by flow cytometry.

In vitro and in vivo effect of rimiducid on killing of CaspaCIDe-containing T-cells. (Left) BPX-501 T cells made from six healthy donors were cultured for 24 hours with log-dilutions of rimiducid (0 – 10 nM). (Right) Five groups of three immune deficient mice were injected intravenously with 10 million human BPX-501 T cells followed by varying doses of rimiducid (0 – 5 mg/kg) 24 hours later. One day later, the spleens were isolated and analyzed for the presence of BPX-501 T cells by flow cytometry.

 

 

 

 

 

 

 

 

In addition to our internal preclinical and clinical development activities, we have selectively entered into agreements with cancer research centers that specialize in cellular immunotherapy to allow the use of our CaspaCIDe safety switch with the collaborators’ CAR-T product candidates. While we are not the sponsor of these clinical trials, we believe that they may facilitate the adoption of CaspaCIDe in the CAR T cell setting and provide opportunities for license arrangements of our technology in the future.