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Adaptimmune today announces the release of preliminary results from an early phase clinical study using patients’ own T cells that have been genetically altered to attack multiple myeloma (MM) cells. Lead investigators for the study presented in three separate sessions at the annual meeting of the American Society of Hematology (ASH).

The clinical study was designed as a single arm open label study where patients are given standard of care (autologous stem cell transplant) in conjunction with engineered T cells. The critical step in this new approach is that the infused T cells have been genetically engineered to carry receptors that help the T cells recognize and attack a tumor, while sparing healthy tissue.

Study objectives are to evaluate the safety, bioactivity and anti-tumor effect of infusion of patients’ own T cells that have been genetically modified to express a high affinity T cell receptor (TCR) specific for a type of tumor antigen (protein) known as a cancer testis antigen (CT antigen). The target CT antigens in the study are NY-ESO-1 and LAGE-1.

The initial six patient phase is complete and, based on the encouraging preliminary results, the study was extended to a target enrollment of 26 patients. To date, a total of 15 patients have been enrolled and have received the engineered T cells; of these, 13 have been assessed at day 100 and 11 patients have reached a minimum of six month follow-up for assessment of tumor response to the treatment.

Multiple myeloma is a hematologic cancer localized to the bone marrow, and is currently incurable in most patients. With standard therapy, long-term response rates are low, and the median survival for patients with this disease is three to five years.

The clinical study focuses on this unmet medical need and includes patients who have received prior treatment for their myeloma or who have disease considered to be high risk, and who are eligible for an autologous stem cell transplant (auto-SCT). Auto-SCT is the transplant of a patient’s own stem cells, which is a standard of care for treatment of multiple myeloma in the U.S. Infusion of the gene modified T cells occurs just following auto SCT.

Dr. Aaron Rapoport, the Chair of the clinical study, presented abstract 472 entitled “Adoptive Transfer of Gene-Modified T-Cells Engineered to Express High-Affinity TCRs for Cancer Testis Antigens (CTAs) NY-ESO-1 or Lage-1, in MM Patients Post Auto-SCT”. He reports that infusions of engineered T cells have been well tolerated. The overall best response rate at 100 days is 77%, which is encouraging when compared to the rate expected from auto-SCT alone (33%-69% as reported in contemporary published studies). Of the 15 patients treated to date, 10 have ongoing responses, and 5 have progressed. In cases of disease progression, a concomitant loss or reduction of engineered T cells, or a loss of antigen positivity on recurring tumor, has been observed. Consequently, the protocol has been modified to allow for additional infusions provided the patient’s tumor continues to express target antigen. These infusions will be administered outside of the transplant setting.

“I am encouraged by the clinical data, particularly after having the opportunity to carry out a detailed review ahead of this meeting,” says Dr. Rapoport. “I look forward to continuing this research and having the opportunity to evaluate the engineered cells outside of the transplant setting.”

Dr. Michael Kalos, the lead correlative scientist on the study, presented abstract 755 entitled “Prolonged T Cell Persistence, Homing to Marrow and Selective Targeting of Antigen Positive Tumor in Multiple Myeloma Patients Following Adoptive Transfer of T Cells Genetically Engineered to Express an Affinity-Enhanced T Cell Receptor against the Cancer Testis Antigens.” He reports robust persistence of engineered T cells; in all cases cells are detectable at least six months post infusion, and expression of the engineered TCR on T cells is detected up to one year post infusion. Engineered T cells also traffic to the bone marrow, the site of tumor in MM, and have been detected in the marrow of all patients. The ratio of tumor antigen to tumor cells remains below baseline in all patients, except in cases where loss of engineered T cells occurs.

“The preliminary data to date support the anticipated mechanism of action for the engineered cells,” says Dr. Kalos. “The engraftment data, particularly the trafficking to marrow, is very encouraging, and the disappearance of antigen in responding patients and its correlation with engineered cell persistence supports the concept that the engineered T cells are providing an additive effect to the transplant.”

In addition, Dr. Carl June, study sponsor and recipient of the prestigious 2012 Ernest Beutler Award for major translational advances, also presented a summary of the study findings at the Beutler Lecture today. “This study is an important contribution to a growing field of genetic therapies showing exciting promise both as a therapy for myeloma patients and also patients with other hematological and solid malignancies,” states Dr. June.

Enrollment is expected to complete in Q2 2013, with 9 month follow-up and final study analysis completed by Q1 2014. A second early phase study, designed to evaluate the safety and anti-tumor effect of the engineered T cells outside of the transplant setting, is expected to open in Q2 2013.

Mr. James Noble, CEO of Adaptimmune, also commented, “It has been a privilege to work with this translational team and we are very encouraged by progress to date. We look forward to presenting further data on this and other studies in due course.”

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