Press Release

Study shows T cells engineered with CaspaCIDe improved immune reconstitution

Safety switch activation rapidly resolved GvHD symptoms

HOUSTON--(BUSINESS WIRE)--May 14, 2015-- Bellicum Pharmaceuticals, Inc. (Nasdaq:BLCM), a clinical stage biopharmaceutical company focused on discovering and developing novel cellular immunotherapies, today announced that clinical results from a study conducted by the Center for Cell and Gene Therapy at Baylor College of Medicine, Texas Children’s Hospital, and Houston Methodist using the Company’s Caspase-9 safety switch (CaspaCIDe^®), were simultaneously published in BLOOD and featured today in a late-breaking oral presentation of the American Society of Gene and Cell Therapy (ASGCT) 18^th Annual Meeting in New Orleans.

The DOTTI study assessed immune reconstitution, safety and anti-viral response in patients undergoing T cell-depleted, haploidentical hematopoietic stem cell transplant (haplo-HSCT), followed by administration of donor T cells that were engineered with CaspaCIDe.

Study Highlights:

• All 12 study patients showed more rapid immune reconstitution and reduced infections, compared with reported results in T cell-depleted, haplo-HSCT procedures.
• Four cases of Graft-versus-host disease (GvHD) were reported; all were resolved with no recurrence following administration of rimiducid.
• One GvHD case analogous to cytokine release syndrome (CRS) or systemic inflammatory response syndrome (SIRS) associated with the cell transplant was reported; it was resolved within 2 hours following a single infusion of rimiducid, with no recurrence.
• Engraftment and anti-viral immunity were preserved in patients even after eliminating T cells causing GvHD, showing rimiducid (AP1903) is selective in eliminating alloreactive T cells.

“Removal of T cells is recommended in the haploidentical transplant setting to avoid GvHD, but their removal can increase the risk of graft rejection, relapse and viral and other opportunistic infections,” said Dr. Xiaoou Zhou, post-doctoral associate at the Center for Cell and Gene Therapy. “It has been difficult to develop a single approach that overcomes these challenges. This study shows that infusing larger numbers of haploidentical donor T cells engineered with CaspaCIDe leads to better infection control. We also showed that if GvHD occurs, it can be rapidly controlled and eliminated by removing alloreactive cells with rimiducid in vivo, and that the productive, anti-viral and anti-cancer cells remain, repopulate and maintain immunity. This is a significant finding that can lead to broader adoption of curative haploidentical transplants for cancers and genetic blood disorders. It also suggests that CaspaCIDe has great potential with CAR T and TCR therapies, where rapid control of dangerous T cell-mitigated toxicities, such as cytokine release syndrome, is needed to achieve wide adoption.”

Study Details

Twelve patients undergoing haplo-HSCT to treat blood cancers were treated in dose escalating cohorts with donor T cells engineered with the CaspaCIDe safety switch. The engineered T cells were infused 30 to 90 days following stem cell transplant. Patients were monitored for safety, immune reconstitution and ability of transplanted T cells to fight viral infections. Rimiducid was infused in patients presenting with confirmed Grade I or II GvHD.

Four of the 12 patients developed acute GvHD, and all were successfully treated with rimiducid with no GvHD recurrence. Results also showed that the transplanted engineered T cells provided rapid protection from the viruses EBV, CMV, VZV, HHV6, and BKV. Although administration of rimiducid resulted in a temporary reduction in circulating virus-specific T cells, those cells subsequently recovered and anti-viral activity was maintained.

One patient developed the signs and symptoms of cytokine release syndrome or systemic inflammatory response syndrome associated with the cell transplant. On day 18 following infusion of the engineered T cells, the patient experienced a fever of 105 degrees Fahrenheit, developed associated skin rash and diarrhea, and had high levels of circulating cytokines, including IL-6. Within 2 hours of infusion with rimiducid, the patient’s temperature normalized, skin rash improved and elevated plasma cytokine levels declined without further treatment.

“CaspaCIDe may improve haploidentical stem cell transplant outcomes, while giving doctors a potential means for rapidly controlling and eliminating GvHD,” said Tom Farrell, President and Chief Executive Officer of Bellicum Pharmaceuticals. “These are very strong clinical results that illustrate why we believe our controlled cell therapies can potentially transform cell transplants as an effective and often curative treatment for a wide variety of cancers and genetic blood disorders. Bellicum is extending this research with BPX-501, with a focus on improving immune reconstitution in haploidentical HSCT.”

About Bellicum Pharmaceuticals

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. Bellicum 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.

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. Bellicum 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 -501, CaspaCIDe and our expectations regarding our other programs. Various factors may cause differences between Bellicum’s expectations and actual results as discussed in greater detail in Bellicum’s filings with the Securities and Exchange Commission, including without limitation our annual report on Form 10-K for the year ended December 31, 2014. Any forward-looking statements that Bellicum makes in this press release speak only as of the date of this press release. Bellicum assumes no obligation to update our forward-looking statements whether as a result of new information, future events or otherwise, after the date of this press release.

Source: Bellicum Pharmaceuticals, Inc.

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