On December 29, 2016 Prima BioMed Ltd (ASX: PRR; NASDAQ: PBMD) ("Prima" or the "Company") reported interim data for its TACTI-mel (Two ACTive Immunotherapeutics in melanoma) clinical trial program for IMP321 in unresectable or metastatic melanoma patient (Press release, Prima Biomed, DEC 29, 2016, View Source [SID1234517233])s. The Database Safety Monitoring Board (DSMB) confirmed that IMP321 is safe and well tolerated at the first dose level when used in combination with a PD-1 blocking antibody and dose escalation can continue as planned.

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In this first-in-man combination Phase I study, IMP321 is combined with the PD-1 checkpoint inhibitor pembrolizumab (KEYTRUDA). Patients with unresectable or metastatic melanoma that had suboptimal or no responses to KEYTRUDA have been receiving IMP321 plus KEYTRUDA to help boost their immune responses and increase the tumour response rate to KEYTRUDA.

Initial data show no safety concerns from the combination with IMP321 at 1 mg dosage. No drug related serious adverse events have been reported and the DSMB approved the continuance of the dose escalation as planned. The trial will now proceed to the next dose level of 6 mg.

Prima’s Chief Medical Officer, Dr Frédéric Triebel, said: "The majority of metastatic melanoma patients do not respond well to KEYTRUDA, a key reason being that their tumours are poorly infiltrated by activated T cells expressing PD-1. By introducing IMP321, a first-in-class Antigen Presenting Cell (APC) activator, these patients may now be able to repopulate their tumour with more activated T cells which are responsive to KEYTRUDA. So, by combining the effect of ‘pushing the gas’ with IMP321 and ‘releasing the brake’ with KEYTRUDA we propose a rational therapeutic approach to increase the response rate by further boosting anti-tumour CD8 T cells."

Further data updates in terms of safety and activity could be expected throughout 2017.

About IMP321
IMP321, a first-in-class Antigen Presenting Cell (APC) activator based on the immune checkpoint LAG-3, represents one of the first proposed active immunotherapy drugs in which the patient’s own immune system is harnessed to respond to tumour antigenic debris created by chemotherapy. As an APC activator IMP321 boosts the network of dendritic cells in the body that can respond to tumour antigens for a better anti-tumour CD8 T cell response.

Aptose Biosciences Provides Update on APTO-253 Development

On December 29, 2016 Aptose Biosciences Inc. (NASDAQ:APTO) (TSX:APS), a clinical-stage company developing new therapeutics and molecular diagnostics that target the underlying mechanisms of cancer, reported an update on the development of APTO-253, its investigational compound for acute myeloid leukemia (AML) (Press release, Aptose Biosciences, DEC 29, 2016, View Source [SID1234517231]). The company has successfully manufactured multiple batches of a new drug product formulation for APTO-253, including a batch that has been stable and soluble for over six months. However, Aptose will have to repeat the production of the fourth batch, a 40L batch that was the intended clinical supply, because of a correctable engineering design incompatibility during the filling process. Aptose expects the batch records and release specifications from such a new batch, along with the stability and sterility data, to be provided to the FDA during the first quarter of 2017.

The need to strengthen the filling process is not a reflection on the drug substance or new formulation, both of which continue to perform favorably. Indeed, the new formulation demonstrates an increase of three times plasma drug exposure as compared to the prior formulation and may have the potential to create additional intellectual property for the company. Aptose also demonstrated that APTO-253 acts by inhibiting expression of the c-Myc oncogene without toxicity to normal bone marrow and blood cells, thereby potentially increasing the likelihood of application to additional cancer indications.

"We remain committed to the development of APTO-253, a small molecule agent that may provide benefit to an important patient population," said William G. Rice, Ph.D., Chairman, President and Chief Executive Officer. "While we have encountered delays in manufacturing activities, we also have continued mechanistic and pharmacokinetic testing of APTO-253 which heighten its viability.

In parallel, we also continue to advance the development of CG’806, an exciting preclinical compound for patients with FLT3-driven AML and certain B-cell malignancies."

In November of last year, Aptose’s phase 1b trial of APTO-253 was temporarily suspended because of the report of an operational difficulty with an IV infusion pump at a clinical site. The company has spent the year identifying the root cause of the clogging issue and actively evaluating multiple formulation and production methodologies in order to improve solubility and stability characteristics and select the best approach to optimizing the delivery of the product to patients with the goal of re-entering the clinic. Aptose is currently working on submitting information requested by the FDA as a result of the development of a new drug product that does not cause filter clogging or pump stoppage during simulated infusion studies.

ImmunoGen Announces Mirvetuximab Soravtansine Phase 1 Expansion Cohort Results in Platinum-Resistant Ovarian Cancer Published in the Journal of Clinical Oncology

On December 28, 2016 ImmunoGen, Inc. (Nasdaq:IMGN), a leader in the expanding field of antibody-drug conjugates (ADCs) for the treatment of cancer, reported that results from the Phase 1 expansion cohort evaluating mirvetuximab soravtansine (IMGN853) in patients with folate receptor alpha (FRα)-positive platinum-resistant ovarian cancer were published in the Journal of Clinical Oncology (Press release, ImmunoGen, DEC 28, 2016, View Source [SID1234517221]). The data demonstrate the potential clinical benefit of mirvetuximab soravtansine for the treatment of platinum-resistant ovarian cancer.

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"Standard single-agent therapy for patients with platinum-resistant ovarian cancer typically has a response rate below 20% and median progression-free survival below four months," said Kathleen Moore, M.D., Associate Professor, Stephenson Cancer Center, University of Oklahoma, and lead author of the publication. "Mirvetuximab soravtansine generated encouraging efficacy and tolerability data in the Phase 1 trial that suggest the potential to improve clinical outcomes for this patient population."

The Phase 1 expansion cohort enrolled 46 patients with platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer whose tumors were positive for FRα. Patients were dosed with mirvetuximab soravtansine once every three weeks. Mirvetuximab soravtansine demonstrated single-agent activity in the 46-patient cohort with a 26% confirmed response rate and median progression free survival (PFS) of 4.8 months. In a subset of 23 patients with low, medium or high FRα, who had received three or fewer prior lines of therapy, there was a 39% objective response rate (ORR) and median PFS of 6.7 months. On the basis of the study findings and additional data demonstrating the importance of FRα expression levels with mirvetuximab soravtansine, the Company has designed the Phase 3 FORWARD I study to enroll patients with platinum-resistant ovarian cancer with one to three prior therapies and with medium or high FRα. This group of patients in the Phase 1 expansion cohort exhibited a 44% ORR and a median PFS of 6.7 months.1

Mirvetuximab soravtansine exhibited a manageable safety profile. Adverse events (AEs) were generally mild with the majority being grade 1 or grade 2 (least severe grades). The most commonly observed AEs were diarrhea, blurred vision, nausea, and fatigue.

"These results demonstrate that mirvetuximab soravtansine is active in platinum-resistant ovarian cancer, with encouraging response rates and progression-free survival combined with a manageable safety profile," said Anna Berkenblit, M.D., Vice President and Chief Medical Officer of ImmunoGen. "On the basis of these findings, we have moved confidently into a Phase 3 registration study evaluating this promising agent against the standard of care in the platinum-resistant setting. In addition, we are evaluating combination regimens to assess mirvetuximab soravtansine in expanded patient populations and will begin reporting data from these combinations in mid-2017."

The publication, "Safety and Activity of Mirvetuximab Soravtansine (IMGN853), a Folate Receptor Alpha-Targeting Antibody-Drug Conjugate, in Platinum-Resistant Ovarian, Fallopian Tube, or Primary Peritoneal Cancer: A Phase I Expansion Study," is available on the Journal of Clinical Oncology website.

About Mirvetuximab Soravtansine

Mirvetuximab soravtansine (IMGN853) is the first FRα-targeting ADC. It uses a FRα-binding antibody to target the ADC specifically to FRα-expressing cancer cells and a potent anti-tumor agent, DM4, to kill the targeted cancer cells.

Mirvetuximab soravtansine is ImmunoGen’s lead program and is now in Phase 3 testing as a single agent for the treatment of platinum-resistant ovarian cancer. The candidate is also being assessed in combination regimens for both platinum-resistant and platinum-sensitive disease in Phase 1b/2 FORWARD II trial.

About Ovarian Cancer and FRα

In 2016, approximately 22,300 new cases of ovarian cancer will be diagnosed in the U.S. and more than 14,200 women will die from the disease.2 ImmunoGen estimates that 60% of ovarian cancer cases have medium or high FRα expression.

Standard first-line therapy for ovarian cancer is a platinum-based regimen. Once the cancer becomes platinum-resistant, treatment options include single-agent cytotoxic therapies such as pegylated liposomal doxorubicin, paclitaxel, or topotecan.

Fortress Biotech Announces Publication on MB-101 (IL13Ra2-specific CAR T cells) for the Treatment of Glioblastoma in New England Journal of Medicine

On December 28, 2016 Fortress Biotech, Inc. (NASDAQ: FBIO) ("Fortress"), a biopharmaceutical company dedicated to acquiring, developing and commercializing novel pharmaceutical and biotechnology products, reported that a patient case study from the Phase 1 clinical trial of MB‐101 (IL13Rα2‐specific, Chimeric Antigen Receptor engineered CAR T cells [CAR T cells]) for the treatment of glioblastoma (GBM) will be published in the December 29 edition of the New England Journal of Medicine (Press release, Fortress Biotech, DEC 27, 2016, View Source;FID=1001218519 [SID1234517222]). MB‐101 is the lead development candidate of Mustang Bio, Inc., a Fortress Company.  

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The research, led by Stephen J. Forman, M.D., Christine Brown, Ph.D., and chief of neurosurgery Behnam Badie, M.D. at City of Hope, describes a 50‐year‐old male patient with recurrent multifocal glioblastoma and spinal tumors who had failed standard‐of‐care tumor resection, radiation therapy and temozolomide. The patient received multiple infusions of MB‐101, which was developed from his own genetically modified T cells, first into the resected tumor cavity as part of the Phase 1 study, and then, following tumor growth distal to the resected cavity, under a compassionate use protocol the patient received MB‐101 infusions into the ventricular system. This extremely novel approach had not been previously tested.

After treatment with intraventricular MB‐101, regression of all intracranial and spinal tumors was observed, along with corresponding increases in levels of cytokines and immune cells in the cerebrospinal fluid. During intraventricular treatment, systemic dexamethasone was gradually eliminated, and the patient returned to normal life and work activities. The clinical response continued for 7.5 months after the initiation of MB‐101. Infusions of MB‐101 were well tolerated and not associated with any toxic effects of grade three or higher.

Dr. Lindsay A. Rosenwald, Fortress Biotech’s Chairman, President and Chief Executive Officer, said, "We are excited to share this unprecedented research conducted by Mustang’s partners at City of Hope, which confirms the potential of MB‐101 to be a breakthrough immunotherapeutic targeted against GBM, an almost universally fatal brain tumor. MB‐101’s compelling clinical activity adds to the growing pipeline of therapies developed by our Fortress Companies that have the potential to transform the treatment of life‐threatening diseases."

Michael S. Weiss, Mustang Bio’s Executive Chairman, commented, "We are extremely encouraged by the response seen in this patient.  As the first patient ever to receive intraventricular delivery of CAR T cells for brain tumors, we see this as proof of concept that CAR T cells can be delivered safely and with remarkable effect to patients with GBM.  This robust response has prompted the expansion of our Phase 1 study to evaluate intraventricular administration in a larger cohort of patients.  Given the poor outcomes for patients with GBM, we believe if we see additional patients with this type of response that we can explore a possible accelerated approval pathway, similar to that proposed by some of the other CAR T companies, which are targeting different forms of cancer."

Dr. Brown, Heritage Provider Network Professor in Immunotherapy, associate director of the T Cell Therapeutics Research Laboratory at City of Hope, and lead author on the case study, said, "This clinical experience provides remarkable evidence of the potential of CAR T cell immunotherapy to improve the treatment of patients with aggressive brain tumors, while preserving neurological function and minimizing toxic side effects seen with other therapies. We are very encouraged by the regression of all brain and spinal lesions, a response that has been unparalleled to date and may warrant future studies of MB‐101 in a wide variety of patients. We look forward to continuing our work with Mustang on this promising therapy."

City of Hope is evaluating MB‐101 in an ongoing Phase 1 study in patients with recurrent and refractory malignant GBM. For additional information, visit NCT02208362.  

About Glioblastoma multiforme (GBM)
Glioblastomas (GBM) are tumors that arise from astrocyte cells that make up the supportive tissue of the brain. These tumors are usually highly malignant (cancerous) because the cellsreproduce quickly and they are supported by a large network of blood vessels. GBM isthe most common brain and central nervoussystem (CNS) malignancy, accounting for 15.1 percent of all primary brain tumors, and 55.1 percent of all gliomas (Brain Tumor Statistics. American Brain Tumor Association. December 2015). There were roughly 27,000 new glioblastoma cases worldwide in 2015 (Global Data. December 2016).  

While GBM is a rare disease (2‐3 cases per 100,000 person life years in the U.S. and EU), it is quite lethal with five‐ year survival rates historically less than 10 percent. Chemotherapy with temozolomide and radiation are shown to extend median survival from approximately 12 to 15 months, while surgery remains the standard of care. GBM remains difficult to treat due to the inherent resistance of the tumor to conventional therapies. Treatment is further complicated by the susceptibility of the brain to damage, the difficulty of the brain in repairing itself and the limitations of drugs in crossing the blood‐brain barrier. Immunotherapy approaches targeting brain tumors offer promise over conventional treatments.

About MB‐101 (IL13Rα2‐specific CAR T cells)
IL13Rα2 is an attractive target for CAR T therapy asit haslimited expression in normal tissue but is over‐expressed on the surface of the majority of GBM cells. CAR T cells are designed to express a membrane‐tethered IL‐13 receptor ligand (IL‐13) incorporating a single‐point mutation that provides high affinity for IL13Rα2 and reduces binding to IL13Rα1 in order to reduce healthy tissue targeting.  

Mustang is developing MB‐101 as an optimized CAR T product incorporating enhancements in CAR design and T cell engineering to improve antitumor potency and T cell persistence. MB‐101 includes a second‐generation hinge optimized CAR containing mutations in the IgG4 linker to reduce off‐target Fc interactions, the 41BB (CD137) co‐ stimulatory signaling domain for improved persistence of CAR T cells and extracellular domain of CD19 as a selection/safety marker. To further improve persistence, central memory T cells are enriched and genetically engineered using a manufacturing process that limits ex vivo expansion to reduce T cell exhaustion and maintain a memory T cell phenotype.

PharmaCyte Biotech’s Cannabinoid Therapy May Offer Potential for Childhood Brain Cancers

On December 27, 2016 PharmaCyte Biotech, Inc. (OTCQB:PMCB), a clinical stage biotechnology company focused on developing targeted treatments for cancer and diabetes using its signature live-cell encapsulation technology, Cell-in-a-Box, reported that recent research performed at the Ann and Robert H. Lurie Children’s Hospital of Chicago and Northwestern University’s Feinberg School of Medicine and published in the journal Child’s Nervous System provides further support for PharmaCyte’s efforts to develop a targeted cannabinoid-based chemotherapy for brain cancer utilizing its technology (Press release, PharmaCyte Biotech, DEC 27, 2016, View Source [SID1234517206]).

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The article, titled "Spontaneous involution of pediatric low-grade gliomas: high expression of cannabinoid receptor 1 (CNR1) at the time of diagnosis may indicate involvement of the endocannabinoid system," showed that activators of the endocannabinoid system offer potential therapeutic opportunities for children with pediatric low-grade gliomas (P-LGG). P-LGGs consist of a mixed group of brain tumors that represent the majority of central nervous system tumors in children. Some P-LGGs exhibit spontaneous shrinking after less than total surgical removal. For the first time, spontaneous shrinking of P-LGG has been suggested to be induced by endocannabinoids.

PharmaCyte’s Chief Executive Officer, Kenneth L. Waggoner, commented, "It is clear that PharmaCyte is on the right track to developing targeted therapies for deadly cancers. The research reported in the journal Child’s Nervous System, as well as other research, continues to demonstrate the anti-cancer properties of cannabinoids. We remain confident that Cell-in-a-Box offers a safe and versatile platform for targeted chemotherapy delivery to cancerous tumors in the brain."

The researchers investigated molecular indicators of spontaneous shrinking in P-LGGs and found that tumors that remained stable or had spontaneous shrinking after surgery had significantly higher levels of expression of the CNR1 gene at the time of diagnosis. They hypothesize that high expression levels of CNR1 make P-LGGs more susceptible to the anticancer effects of normally occurring substances in the body known as endocannabinoids. By extension, plant-derived phytocannabinoid molecules, such as tetrahydrocannabinol (THC) and cannabidiol (CBD), may provide similar effects through their known interaction with endocannabinoid receptors like CNR1.

An abstract of the research may be viewed at: View Source

PharmaCyte’s cannabinoid program at the University of Northern Colorado involves developing a bioengineered cell line that will activate a cannabinoid-based prodrug into its cancer-killing form and then encapsulating these cells using the Cell-in-a-Box encapsulation technology. When the capsules are implanted near the tumor and the cannabinoid prodrug is administered to a patient, targeted chemotherapy results. Prodrugs of THC and CBD are candidates for this program, and brain cancer is PharmaCyte’s initial target using this cannabinoid therapy.

Mark L. Rabe, MD, a member of PharmaCyte’s Medical and Scientific Advisory Board, commented, "It is fascinating to think the body has built-in anti-cancer capabilities in the form of the endocannabinoid system. Cell-in-a-Box offers an ideal way to leverage the endocannabinoid system’s power by delivering THC and CBD to brain tumors like P-LGG in a targeted fashion, with the potential benefits of enhanced efficacy and fewer side effects."