Bellicum Announces Oral Presentation at ASH Showing Improved Potency and Control with CIDeCAR T-Cell Therapies
ASH Annual Meeting also featured poster presentations of GoCAR-T and GoTCR platforms
Supporting preclinical data for CIDeCAR product candidate BPX-401 and GoCAR-T product candidate BPX-601 highlighted
In the oral presentation, “Expression of MyD88/CD40 Drives In Vivo Activation and Proliferation of Chimeric Antigen Receptor Modified T Cells That Can Be Effectively Regulated by Inducible Caspase-9,” Bellicum scientists compared CIDeCARs targeting CD19 or other tumor antigens to CAR constructs based on 4-1BB and CD28. CIDeCAR combines Bellicum’s novel costimulatory domain MC (MyD88/CD40) and the CaspaCIDe® safety switch. Bellicum’s small molecule rimiducid was used to activate the CaspaCIDe safety switch. The CaspaCIDe safety switch was also employed as a “dimmer switch,” titrating the number of CIDeCAR cells in order to remain within a therapeutic window that maximizes both safety and efficacy, for improved clinical benefit.
Study Highlights
Activation:
- The addition of the MC costimulatory domain led to a significant increase in in vivo activation and persistence of the CIDeCAR CAR T cells when compared to CARs constructed with conventional costimulatory domains CD28 and 4-1BB.
- Studies also showed that CAR T cells with the MC costimulatory domain eliminated cancer cells faster in animal models than CARs using CD28 or 4-1BB.
Safety:
- In CD19 and HER2 animal models, the majority of CAR T cells can be eliminated if needed, leading to rapid recovery from cytokine release-like syndrome, without tumor relapse.
- Experiments also demonstrate that the CaspaCIDe safety switch can be titrated. Lower concentrations of small molecule activator rimiducid led to elimination of only a portion of circulating CAR T cells, including possibly the most active cells, without losing the antitumor effect of treatment.
GoCAR-T™ and GoTCR™ Poster Presentations
Two additional poster presentations1,2 at ASH featured the Company’s GoCAR-T and GoTCR technologies. GoCAR-T technology uses rimiducid to control persistence of CAR-T cells in vivo for therapeutic effect. In animal experiments targeting CD19 and Prostate Stem Cell Antigen (PSCA), Bellicum scientists demonstrated that a single IV injection of GoCAR-T cells containing the proprietary iMC (inducible MyD88/CD40) activation switch could eliminate large, established solid tumors and lymphomas. Administration of rimiducid stimulated the survival and proliferation of GoCAR-T cells, which may allow more effective therapy of solid tumors in patients.
In an additional poster session, Bellicum scientists used the same iMC activation switch to complement HLA-A2/Preferentially Expressed Antigen in Melanoma (PRAME)-specific TCR-modified T cells to create “GoTCR”s that also could be activated by rimiducid, similar to the GoCAR-T platform. PRAME-targeted GoTCRs were active against PRAME-expressing tumors in vitro and in vivo. Activation with weekly administration of rimiducid led to more effective tumor control. In this application of the CID technology, toxicity is controlled by the cessation of rimiducid administration, acting like “lifting one’s foot off of a gas pedal,” without the loss of tumor control.
“These preclinical data support the advancement of our product
candidates BPX-401 and BPX-601 into clinical trials. We are also excited
about the potential of our GoTCR platform to address the limitations of
TCR therapy by enabling control over the cells’ proliferation and
persistence,” commented
1 Foster A, Mahendravada A, Shinners N, et al. “Inducible
MyD88/CD40 allows rimiducid-dependent activation to control
proliferation and survival of chimeric antigen receptor-modified T
cells.” 2015 Annual Meeting of the
2 Hoang T, Foster A, Lu A, et al. “Inducible MyD88/CD40
enhances proliferation and survival of PRAME-specific TCR-engineered T
cells and increases anti-tumor effects in myeloma 2015.” Annual Meeting
of the
About
Bellicum is a clinical stage biopharmaceutical company focused on discovering and developing novel cellular immunotherapies for various forms of cancer, including hematological cancers and solid tumors, as well as orphan inherited blood disorders. The Company is using its proprietary Chemical Induction of Dimerization, or CID, technology platform to engineer and control components of the immune system in real time. The Company is developing next-generation product candidates in some of the most important areas of cellular immunotherapy, including hematopoietic stem cell transplantation, or HSCT, CAR T cell therapy, and dendritic cell vaccines.
*CaspaCIDe® is a trademark registered with the U.S. Patent and Trademark Office. CIDeCAR™, GoCAR-T™ and GoTCR™ are trademarks of Bellicum Pharmaceuticals.
Forward-Looking Statement
This press release contains forward-looking statements for purposes of
the safe harbor provisions of the Private Securities Litigation Reform
Act of 1995. We may, in some cases, use terms such as "predicts,"
"believes," "potential," "proposed," "continue," "estimates,"
"anticipates," "expects," "plans," "intends," "may," "could," "might,"
"will," "should" or other words that convey uncertainty of future events
or outcomes to identify these forward-looking statements.
Forward-looking statements include statements regarding our intentions,
beliefs, projections, outlook, analyses or current expectations
concerning, among other things: the timing of our clinical trials and of
our research and development activities relating to BPX-401 and BPX-601;
the effectiveness and success of our research and development activities
relating to our GoCAR-T and GoTCR platforms; and the effectiveness of
BPX-401 and BPX-601 and their possible range of applications and
potential curative effects and safety profiles. Various factors may
cause differences between Bellicum’s expectations and actual results as
discussed in greater detail in Bellicum’s filings with the
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Source:
Investors:
Bellicum Pharmaceuticals, Inc.
Alan Musso,
832-384-1116
Chief Financial Officer
amusso@bellicum.com
or
Media:
For
Bellicum Pharmaceuticals, Inc.
Brad Miles, 917-570-7340
bmiles@bmccommunications.com
or
Amy
Bonanno, 914-450-0349
abonanno@bmccommunications.com
