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U.S. Food and Drug Administration Accepts for Priority Review the Biologics License Application for Empliciti (elotuzumab) for the Treatment of Multiple Myeloma in Patients Who Have Received One or More Prior Therapies

On September 1, 2015 Bristol-Myers Squibb Company (NYSE:BMY) and AbbVie (NYSE:ABBV) reported the U.S. Food and Drug Administration (FDA) has accepted for priority review the Biologics License Application (BLA) for Empliciti (elotuzumab), an investigational Signaling Lymphocyte Activation Molecule (SLAMF7)-directed immunostimulatory antibody, for the treatment of multiple myeloma as combination therapy in patients who have received one or more prior therapies (Press release, Bristol-Myers Squibb, SEP 1, 2015, View Source [SID:1234507365]). Empliciti was previously granted Breakthrough Therapy Designation, which according to the FDA, is intended to expedite the development and review of drugs for serious or life-threatening conditions. The European Medicines Agency (EMA) also recently validated for review the Marketing Authorization Application for Empliciti, granting it accelerated assessment.

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Bristol-Myers Squibb has proposed the name Empliciti which, if approved by health authorities, will serve as the brand name for elotuzumab.

"Bristol-Myers Squibb is delighted by the approach both agencies have taken to review the Empliciti applications as it underscores the unmet medical need in the treatment of multiple myeloma and the role Immuno-Oncology may play," said Michael Giordano, M.D., senior vice president, Head of Oncology Development, Bristol-Myers Squibb. "The acceptance of our applications by the FDA and EMA brings Bristol-Myers Squibb’s Immuno-Oncology science a step closer to helping patients with hematologic malignancies."

The filing acceptance is primarily supported by data from the ELOQUENT-2 trial, a Phase 3, randomized, open-label study, which evaluated Empliciti in combination with lenalidomide and dexamethasone versus lenalidomide and dexamethasone alone. The results of this trial were published in The New England Journal of Medicine on June 2. Additionally, the filing was supported by data from study CA204-009, a Phase 2, randomized, open-label study which evaluated Empliciti with bortezomib and dexamethasone versus bortezomib and dexamethasone alone. These Phase 2 results were presented in an oral session (Abstract #S103) at the 20th Congress of the European Hematology Association (EHA) (Free EHA Whitepaper).

"AbbVie is encouraged by the FDA’s decision to award priority review to this application," said Gary Gordon, M.D., vice president, oncology clinical development, AbbVie. "AbbVie is committed to the development of novel treatment options for people affected by cancer."

About Empliciti

Bristol-Myers Squibb has proposed the name Empliciti which, if approved by health authorities, will serve as the brand name for elotuzumab. Elotuzumab is an investigational immunostimulatory antibody targeted against SLAMF7, a cell-surface glycoprotein that is highly and uniformly expressed on myeloma cells and Natural Killer (NK) cells, but is not detected on normal solid tissues or on hematopoietic stem cells. The safety and efficacy of elotuzumab have not been evaluated by the FDA or any other health authority.

Bristol-Myers Squibb and AbbVie are co-developing elotuzumab, with Bristol-Myers Squibb solely responsible for commercial activities.

About Multiple Myeloma

Multiple myeloma is a hematologic, or blood, cancer that develops in the bone marrow. It occurs when a plasma cell, a type of cell in the soft center of bone marrow, becomes cancerous and multiplies uncontrollably. Despite advances in multiple myeloma treatment over the last decade, it remains a largely incurable disease with only 45% of patients surviving five years after diagnosis. A common characteristic for many patients is that they experience a cycle of remission and relapse, in which they stop treatment for a short time, but eventually return to a treatment shortly after. Following relapse, less than 20% of patients are alive after five years. It is estimated that annually more than 114,200 new cases of multiple myeloma are diagnosed globally and annually more than 79,000 people die from the disease globally.

Adaptimmune Expands Trial of T-cell Therapy for Synovial Sarcoma and Achieves Clinical Milestones

On September 1, 2015 Adaptimmune Therapeutics plc (Nasdaq: ADAP), ("Adaptimmune" or the "Company"), a clinical stage biopharmaceutical company focused on the use of T-cell therapy to treat cancer, reported that the first patient has been dosed in its expanded Phase I/II trial of its affinity enhanced T-cell receptor (TCR) therapeutic targeting the NY-ESO-1 cancer antigen in synovial sarcoma patients (Press release, Adaptimmune, SEP 1, 2015, View Source [SID:1234507364]).

Based on encouraging results in the first cohort of 10 patients, presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) annual meeting in April 2015, the trial is being expanded to encompass an additional 20 patients in two further cohorts.

The expansion of Adaptimmune’s trial also triggers two milestone payments from GlaxoSmithKline (GSK). Adaptimmune is collaborating with GSK for the development of its NY-ESO TCR program through a strategic cancer immunotherapy partnership announced in June 2014. Under the terms of the agreement, GSK has an exclusive option to license Adaptimmune’s NY-ESO TCR therapeutic and upon exercise would assume full responsibility for further development and commercialization of the therapeutic.

"We are encouraged by the promising data from the first cohort of patients and pleased to have commenced enrollment into the next two cohorts of this study," commented Dr. Rafael Amado, Adaptimmune’s Chief Medical Officer. "Metastatic synovial sarcoma is largely incurable, with as few as 20 percent of patients surviving for more than two years after diagnosis. In the first cohort of this trial, we saw evidence of antitumor activity resulting from treatment with our NY-ESO TCR therapeutic in a solid tumor setting. These early data provide confidence to expand the trial in these patients who currently lack proven, effective treatment options."

Synovial sarcoma is a cancer of the connective tissue and a type of solid tumor primarily affecting adolescents and young adults. Most metastatic soft tissue sarcomas are currently incurable – 75 to 80 percent of patients do not survive past two to three years – and there are limited treatment options for unresectable and recurrent synovial sarcoma, which is nearly always fatal.

Adaptimmune’s clinical study includes synovial sarcoma patients who have received standard first line therapy containing ifosfamide and/or doxorubicin and who are intolerant or no longer responding to the regimen, and whose tumor expresses a tumor antigen known as NY-ESO-1. The NY-ESO-1 antigen is believed to be present in 60 to 70 percent of synovial sarcoma patients.

The primary objectives of the study are to determine the safety of adoptively transferred autologous T cells expressing an affinity enhanced T cell receptor that recognizes the NY-ESO-1 antigen in HLAA*0201, HLA-A*0205, and/or HLA-A*0206 positive patients with unresectable, metastatic or recurrent synovial sarcoma. Secondary objectives include the determination of efficacy through response rate and duration of response.

All eligible patients will be treated with lymphodepletive chemotherapy followed by administration of Adaptimmune’s NY-ESO TCR therapeutic. In the first cohort, patients whose tumor expressed NY-ESO-1 at high levels received a single course of cyclophosphamide and fludarabine for lymphodepletion prior to administration of Adaptimmune’s NY-ESO TCR therapeutic. Cohort 2 will enroll patients whose tumor expresses lower levels of the NY-ESO-1 antigen and who will receive the same treatment as patients in the first cohort. Cohort 3 will enroll patients whose tumor expresses high levels of the NY-ESO-1 antigen and will study the removal of fludarabine as part of the lymphodepletion regimen. Both cohorts are expected to open concurrently.
For more information on the trial, visit ClinicalTrials.gov at: View Source (Identifier: NCT01343043).

Adaptimmune is currently running trials in multiple cancers across the U.S. targeting the NY-ESO-1 cancer antigen in both solid and hematologic cancers. As of May 30, 2015, 85 patients had been treated with Adaptimmune’s NY-ESO TCR therapeutic: 47 under Adaptimmune’s IND, and 38 under a National Cancer Institute IND. Data from the Company’s Phase I/II study in synovial sarcoma were presented at AACR (Free AACR Whitepaper). As of April 20, 2015, 11 patients in the first cohort had received Adaptimmune’s NY-ESO TCR therapeutic. Of the first 10 patients, six responded, with one complete response. Data from Adaptimmune’s Phase I/II study in 20 patients with advanced multiple myeloma were published in Nature Medicine online on July 20, 2015 and in the print publication on August 6, 2015.

About synovial sarcoma
Soft tissue sarcomas can develop from soft tissues including fat, muscle, nerves, fibrous tissues, blood vessels, or deep skin tissues, and synovial sarcoma, a cancer of the connective tissue around the joints, accounts for approximately 6 to 10 percent of all soft tissue sarcomas. Approximately one third of synovial sarcomas occur in childhood and the peak incidence is in the third decade of life, with 70 percent of sarcomas occurring in patients younger than 40 years old. The majority of patients who develop metastatic soft tissue sarcomas are currently incurable, with 75 to 80 percent of patients not surviving past two to three years. First line therapy typically involves radiotherapy and chemotherapy, as well as surgical resection where possible.

Diffusion Pharmaceuticals CEO to Address American Cancer Society Virginia Research Breakfast. Will discuss the transformative nature of Diffusion’s novel radiation sensitization technology in cancer treatment

On August 31, 2015 Diffusion Pharmaceuticals LLC reported that Company CEO David G. Kalergis, MBA/JD, will be a guest speaker at the 2015 American Cancer Society CAN Virginia Research Breakfast, to be held September 17, 2015 at the Hilton Garden Inn, Glen Allen, Virginia (Press release, Diffusion Pharmaceuticals, AUG 31, 2015, View Source [SID:1234507363]). His topic will be the possible impact of the Company’s transformative new drug trans sodium crocetinate (TSC) on the treatment of cancer in years to come.

The other speakers will be Dr. Gordon D. Grinder, Director, Massey Cancer Center, VCU; Dr. Thomas P. Loughran, Director, UVA Cancer Center; and Dr. Harold Sontheimer, Director Glial Biology, Disease and Cancer Center, VT Carilion Research Center.

Diffusion Pharmaceuticals recently announced results from its recently completed Phase 1/2 TSC GBM study in 59 patients with newly diagnosed glioblastoma (GBM), the most common and aggressive form of primary brain cancer. The results demonstrated that people who received TSC plus radiotherapy and chemotherapy benefited from an improvement in overall survival compared to the historical control group who received radiotherapy and chemo alone.

TSC plus radiotherapy and chemotherapy increased the patients’ chance of survival at two years by 37 percent compared to the control group. In the subgroup of patients considered inoperable, the chance of survival at two years for those who received TSC was increased by over 100 percent. No negative safety findings were observed in the TSC GBM study and no serious adverse events were attributed to TSC in any patient.

TSC currently has FDA Orphan Designations in GBM and metastatic brain cancer. In August 2015, agreement was reached with the FDA on a proposed single Phase 3 GBM study design which, if successful, could support TSC’s approval. Diffusion plans to initiate the study in 1H 2016.

In addition to moving TSC forward for the treatment of GBM, the Company is preparing it for clinical trials in other solid tumor cancer indications.

MabVax Therapeutics HuMab 5B1 Antibody Is Highlighted at Upcoming World Molecular Imaging Congress in Five Separate Presentations

On August 31, 2015 MabVax Therapeutics Holdings, Inc. (OTCQB: MBVX) aclinical stage oncology drug development company reported that the Company’s lead antibody, HuMab 5B1, will be garnering major attention as the subject of five separate presentations during the upcoming World Molecular Imaging Congress (WMIC) being held in Hawaii September 2-5, 2015 (Press release, MabVax, AUG 31, 2015, View Source [SID:1234507361]). Researchers from the Department of Radiology at Memorial Sloan Kettering Cancer Center (MSK) will present results on the use of MabVax’s lead antibody as a PET imaging agent and as a radioimmunotherapy agent targeting pancreatic cancer.

Presenters at the WMIC include Jacob Houghton, Ph.D. of MSK, who will present results from two preclinical in vivo studies using the HuMab 5B1 antibody as an ImmunoPET imaging agent in the context of circulating antigen as well as new pretargeted methods for the immunoPET imaging of CA19.9 in murine models of pancreatic cancer. Dalya Abdel-Atti will present the results of using HuMab5B1 in ImmunoPET imaging with newly developed murine organoid models of pancreatic cancer. A third presenter, Jan-Philip Meyer, Ph.D., will present results of using HuMab 5B1 as a pre-targeting agent followed by administration of the short-lived (18F)-NOTA-labeled tetrazine radioligand for PET imaging and in vivo coupling, examining the efficiency of HuMab5B1 in imaging and the reduction in exposure to the radiolabel. All four presentations illustrate the potential utility of the antibody as a next generation imaging agent for pancreatic cancer. Lastly, Ryan Lanning, M.D. Ph.D., will present the results of using HuMab 5B1 as a radioimmunotherapy agent for treatment of pancreatic cancer.

Because five-year survival rates in pancreatic cancer are only 5% and more than half of all patients initially diagnosed already have metastatic disease, the difficulties in identifying distant metastases that often go undetected as well as developing advanced therapeutics to treat this difficult cancer are significant unmet medical needs. These researchers at MSK are on the cutting edge of this technology and may well help develop a new generation of diagnostic and therapeutic agents using HuMab 5B1. Continuing studies of HuMab 5B1 could further demonstrate the utility of a broad technology platform useful both as a imaging and therapeutic agent.

About HuMab 5B1
The fully human antibody HuMab 5B1 was recovered from patients undergoing cancer vaccine treatment at Memorial Sloan-Kettering Cancer Center. The HuMab 5B1 has demonstrated high specificity, affinity, and lack of cross-reactivity with similar antigens. The antibody has also shown potent cancer cell killing capacity and efficacy in animal models of pancreatic, colon, and small cell lung cancers. Ongoing toxicology results continue to demonstrate an acceptable profile in acute and repeat dose studies in animals. MabVax plans to initiate two complementary Phase I clinical trials in the first quarter of 2016. One clinical trial is aimed at determining the safety and potential utility of HuMab 5B1 as a therapeutic agent in subjects with metastatic pancreatic cancer. The second clinical trial is aimed at demonstrating the utility of 89Zr-HuMab 5B1, the Company’s radio-labeled HuMab 5B1 antibody, as a next-generation PET imaging agent for the diagnosis, staging, and management of pancreatic cancer.

Phase 2 Study of Advaxis’s Axalimogene Filolisbac (ADXS-HPV) in Cervical Cancer to be Presented at 2015 AGOS Annual Meeting

On August 31, 2015 Advaxis, Inc. (NASDAQ:ADXS), a clinical-stage biotechnology company developing cancer immunotherapies, reported that final clinical data from Stage 1 of the ongoing two-stage Phase 2 study (GOG-0265) of Advaxis’s lead Lm Technology immunotherapy, axalimogene filolisbac (ADXS-HPV), in patients with persistent or recurrent metastatic (squamous or non-squamous cell) carcinoma of the cervix (PRmCC), will be presented at the American Gynecological & Obstetrical Society (AGOS) annual meeting in Half Moon Bay, Calif. by Tom Hertzog, M.D., Clinical Director at the University of Cincinnati Cancer Institute, on September 17, 2015, at 11:15 a.m. PDT (Press release, Advaxis, AUG 31, 2015, View Source [SID:1234507360]).

"There are limited therapies available in metastatic cervical cancer, particularly for patients who have failed at least one line of therapy," said Dr. Hertzog. "We see the potential for axalimogene filolisbac to fill a significant unmet need in the treatment of this disease and look forward to presenting these Stage 1 data at the AGOS annual meeting."

GOG-0265 is an open-label, single-arm, two-stage Phase 2 study designed to evaluate the safety, tolerability and efficacy of axalimogene filolisbac in approximately 67 patients with PRmCC who have received at least one prior line of systemic therapy. The primary efficacy endpoint is 12-month overall survival rate, with secondary efficacy endpoints of progression-free survival, overall survival and objective tumor response. The primary safety endpoints are the number of patients with dose-limiting toxicities and the frequency and severity of adverse effects.

The trial is being conducted in the United States by the Gynecologic Oncology Group (GOG), now part of NRG Oncology, under the sponsorship of the Cancer Therapy Evaluation Program (CTEP) of the National Cancer Institute (NCI). Further information about the study can be found on ClinicalTrials.gov, using Identifier NCT01266460.

About Cervical Cancer

Cervical cancer is the fourth most common cancer and the most common cause of mortality in women worldwide. In the United States, nearly 13,000 new cases are diagnosed and approximately 4,100 deaths are reported because of cervical cancer. According to the WHO/ICO Information Centre on HPV and Cervical Cancer, about 3.9 percent of women in the U.S. are estimated to harbor high-risk cervical HPV infection at a given time, and 71.7 percent of invasive cervical cancers are attributed to high-risk HPV strains.

About Axalimogene Filolisbac

Axalimogene filolisbac (ADXS-HPV) is Advaxis’s lead Lm Technology immunotherapy candidate for the treatment of HPV-associated cancers and is in clinical trials for three potential indications: invasive cervical cancer, head and neck cancer, and anal cancer. In a completed randomized Phase 2 study in recurrent/refractory cervical cancer, axalimogene filolisbac showed apparent prolonged survival, objective tumor responses, and a manageable safety profile alone or in combination with chemotherapy, supporting further development of the company’s Lm Technology.