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Bellicum Announces Publication in The New England Journal of Medicine Demonstrating Complete Reversal of Serious Immune Condition in Hematopoietic Stem Cell Transplant Patients
Date:11/2/2011

HOUSTON, Nov. 2, 2011 /PRNewswire/ -- Bellicum Pharmaceuticals, Inc. today announced publication in The New England Journal of Medicine of clinical results using a new therapy that demonstrated rapid and complete reversal of graft-versus-host disease (GVHD).  The paper, Inducible Apoptosis as a Safety Switch for Adoptive Cell Therapy, reports on the use of Bellicum's CaspaCIDe technology to eliminate donor T cells causing GVHD, a serious and sometimes fatal complication of allogeneic hematopoietic stem cell transplantation (HSCT), in patients with acute leukemias.  The study was conducted by researchers from the Center for Cell and Gene Therapy at Baylor College of Medicine, Texas Children's Hospital and The Methodist Hospital, using the drug AP1903 provided by Bellicum Pharmaceuticals.

CaspaCIDe technology consists of a drug-inducible "suicide" gene (iCasp9) introduced into therapeutic cells that are subsequently given to patients, and a drug (AP1903) that the physician administers if the cells cause unacceptable toxicity, triggering the suicide gene and leading to their rapid self-elimination.  In today's reported study, T cells with the genetic safety switch were infused into patients to determine if GVHD-causing T cells could be selectively eliminated, while preserving those that may support stem cell engraftment, fight infections and destroy any remaining cancer cells.  

In an accompanying NEJM editorial, Michel Sadelain, MD, PhD, Center for Cell Engineering, Memorial Sloan-Kettering Cancer Center, wrote: "An effective safety switch is needed in a rising spectrum of cell therapies in order to protect against an array of toxic effects," and called the clinical results with iCasp9 "compelling."

Study Details

The study enrolled five patients between the ages of 3 and 17 with acute leukemia, some of whom had previously relapsed.  All patients underwent HSCT from high GVHD risk, partially HLA-mismatched, haploidentical donors.  In all five transplants, the CaspaCIDe suicide gene was inserted into the donor T cells, which were then infused into the patient.  Weeks later, the gene-modified donor cells were detected in the peripheral blood of all five patients, functioning as expected and expanding in number over time.

Four of the five patients went on to develop GVHD and were treated with a single dose of AP1903. Within 30 minutes, 90 percent of the gene modified T cells were eliminated, and the symptoms of GVHD disappeared in all treated patients within 24-48 hours, without the need for steroids.  The surviving T cells re-expanded and continued to help control infections, without recurrence of GVHD, indicating that CaspaCIDe preferentially eliminated those T cells that cause GVHD, as designed.

"Although HSCT can be curative for some cancers, it's a high risk procedure," said Principal Investigator Dr. Malcolm Brenner, Director of the Center for Cell and Gene Therapy.  "Many patients suffer serious complications or death from graft-versus-host disease and its sequellae. Although it is early in development, this technology has shown the ability to selectively eliminate the destructive immune cells causing GVHD, potentially addressing one of the greatest barriers to improved transplant outcomes."

"The results of this first clinical study of CaspaCIDe show that it works quickly and effectively without compromising the function of the cell, and therefore it may have broad application as a safety feature for any cell therapy," said Kevin Slawin, M.D., Chief Medical Officer of Bellicum. "This study also provides clinical proof-in-principle of Bellicum's core chemical induction of dimerization (CID) technology, which we are using elsewhere in our product portfolio to control other clinically important signaling pathways."

CID technology was co-invented by David Spencer, Ph.D., while at Stanford University, further developed by ARIAD (Nasdaq: ARIA), and subsequently licensed by Bellicum. Dr. Spencer, a co-author of the paper and Chief Scientific Officer of Bellicum, commented "the finding that manipulating the interactions of key proteins within the cell using AP1903, an otherwise bio-inert drug, can have such profound clinical implications is an extremely gratifying result."

Hematopoietic Stem Cell Transplantation and GVHD

Replacing a patient's immune system using stem cells from donor bone marrow, peripheral blood or cord blood can be curative for patients with leukemia, lymphoma and other rare genetic disorders.  However, transplant outcomes are often tempered by serious and life threatening complications like graft-versus-host-disease (GVHD), which occurs in 30 - 80 percent of patients, depending on the match.  GVHD occurs when a small portion of the T cells, whether included in the transplant or given separately in a donor lymphocyte infusion, attack the patient's healthy tissue.  These GVHD-causing "alloreactive" T cells comprise only a minority of the otherwise helpful T cells. Following transplant, the recipient usually takes drugs to suppress the attacking T cells, but these come with their own serious adverse effects.  Moreover, 40 percent of GVHD patients do not respond to steroids, the standard of care treatment for GVHD, and 70 percent of those non-responding patients die within 9 months.

About Bellicum Pharmaceuticals

Bellicum Pharmaceuticals, Inc. is developing clinical applications of chemical induction of dimerization (CID), a drug-based remote control technology that extends the physician's reach beyond the point at which a treatment has been administered. Bellicum's mission is to leverage this smart technology to bring safe, effective, innovative cell therapies to market for patients with serious and life threatening diseases. The company's DeCIDe™ vaccines are designed to kill targeted cells by inducing a potent, durable, fully activated antigen-specific T cell immune response. Lead product BPX-101, an autologous DeCIDe™ vaccine, is in clinical development for patients with metastatic castrate resistant prostate cancer (mCRPC). CaspaCIDe™ is a cell therapy safety switch, permitting the rapid elimination of cells in the event of toxicity. CaspaCIDe™ DLI is a donor lymphocyte infusion administered following a hematopoietic stem cell transplant, in which the safety switch may be activated to resolve graft-versus-host disease (GVHD). For more information, visit www.bellicum.com.


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