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 ClinicalTrials.gov: 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.

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."

On December 27, 2016 Seattle Genetics, Inc. (Nasdaq:SGEN), a global biotechnology company, reported that it has received notice from the U.S. Food and Drug Administration (FDA) that a clinical hold or partial clinical hold has been placed on several early stage trials of vadastuximab talirine (SGN-CD33A) in acute myeloid leukemia (AML) (Press release, Seattle Genetics, DEC 27, 2016, View Source;p=RssLanding&cat=news&id=2232880 [SID1234517205]). The clinical holds were initiated to evaluate the potential risk of hepatotoxicity in patients who were treated with SGN-CD33A and received allogeneic stem cell transplant either before or after treatment. Six patients have been identified with hepatotoxicity, including several cases of veno-occlusive disease, with four fatal events. Overall, more than 300 patients have been treated with SGN-CD33A in clinical trials across multiple treatment settings. Seattle Genetics is working diligently with the FDA to determine whether there is any association between hepatotoxicity and treatment with SGN-CD33A, to promptly identify appropriate protocol amendments for patient safety and to enable continuation of these trials.

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The phase 1/2 trial of SGN-CD33A monotherapy in pre- and post-allogeneic transplant AML patients has been placed on full clinical hold. Two phase 1 trials have been placed on partial clinical hold (no new enrollment, existing patients may continue treatment with re-consent). These studies are SGN-CD33A monotherapy, including a subset of older AML patients in combination with hypomethylating agents, and SGN-CD33A combination treatment with 7+3 chemotherapy in newly diagnosed younger AML patients. No new studies will be initiated until the clinical holds are lifted.

Seattle Genetics’ other ongoing trials of SGN-CD33A, including the phase 3 CASCADE trial in older AML patients and phase 1/2 trial in myelodysplastic syndrome, are proceeding with enrollment.

About Vadastuximab Talirine (SGN-CD33A)

Vadastuximab talirine (SGN-CD33A; 33A) is a novel investigational ADC targeted to CD33 utilizing Seattle Genetics’ proprietary ADC technology. CD33 is expressed on most AML and MDS blast cells. The CD33 engineered cysteine antibody is stably linked to a highly potent DNA binding agent called a pyrrolobenzodiazepine (PBD) dimer via site-specific conjugation technology (EC-mAb). PBD dimers are significantly more potent than systemic chemotherapeutic drugs and the EC-mAb technology allows uniform drug-loading onto an ADC. The ADC is designed to be stable in the bloodstream and to release its potent cell-killing PBD agent upon internalization into CD33-expressing cells.

33A was granted Orphan Drug Designation by both the U.S. Food and Drug Administration (FDA) and the European Commission for the treatment of AML. FDA orphan drug designation is intended to encourage companies to develop therapies for the treatment of diseases that affect fewer than 200,000 individuals in the United States.

On December 22, 2016 Ohr Pharmaceutical, Inc. (Nasdaq:OHRP), an ophthalmology research and development company, reported results for its fourth quarter and fiscal year ended September 30, 2016 (Press release, Ohr Pharmaceutical, DEC 22, 2016, View Source [SID1234517187]).

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"Fiscal year 2016 was another highly productive year for Ohr, as we made significant progress in advancing both our lead candidate Squalamine for the treatment of wet AMD as well as our pipeline of sustained release drug candidates," said Jason Slakter, MD, Chief Executive Officer of Ohr. "Building off the Squalamine phase 2 results, we negotiated an SPA with the FDA in advance of commencing the pivotal phase 3 program. This comprehensive phase 3 program is now underway which, if successful, will position us to bring an innovative, meaningful treatment to market that has the potential to improve vision outcomes beyond current therapies and set a new standard of care in wet AMD."

Fiscal 2016 and Recent Corporate Highlights

Reached an agreement on a Special Protocol Assessment (SPA) with the US FDA on the design of Phase 3 trials for Squalamine lactate ophthalmic solution, 0.2% ("Squalamine", also known as OHR-102) for patients with wet AMD.
Appointed David M. Brown, MD to serve as the chair of the Steering Committee for the Phase 3 clinical program of Squalamine in wet-AMD.
Closed a public offering of shares of common stock and warrants resulting in net proceeds of approximately $6.9 million.
Fiscal 2016 Clinical and Development Program Highlights

In September, presented new data from the Phase 2 IMPACT study at the American Society of Retina Specialists (ASRS). Subjects with occult CNV <10mm2 achieved final mean visual acuity outcomes of 71.7 letters with Squalamine combination therapy compared to 67.4 letters with Lucentis monotherapy. The final mean visual acuity outcomes in the combination therapy group translates to approximately 20/40 vision (Snellen equivalent). This underscores the potential of Squalamine combination therapy to allow patients to reach higher levels of visual function and improve their overall quality of life.
In May, presented two posters on the Squalamine Phase 2 IMPACT study and OHR3031 sustained release in vivo studies at the Association for Research in Vision and Ophthalmology (ARVO) Conference.
In April, commenced enrollment in the Phase 3 clinical development program investigating Squalamine as a treatment to improve visual acuity for patients with wet AMD.
The Phase 3 program includes two double-masked, placebo-controlled, multicenter, international studies of Squalamine administered topically twice a day in patients with newly diagnosed wet AMD, in combination with Lucentis injections.
The primary endpoint in both studies is a measurement of visual acuity gain at nine months, which is the most clinically meaningful endpoint for wet AMD patients. Subjects will be followed to two years for safety.
In November 2015, presented new data from the Phase 2 IMPACT Study in Wet-AMD at American Academy of Ophthalmology (AAO) Annual Meeting.
Data showed that the size of occult CNV at baseline, irrespective of a classic CNV component, was the most important factor in predicting treatment success with the combination of Squalamine plus Lucentis. This correlation was not seen in the Lucentis monotherapy group.
Also in November 2015, announced positive preclinical data in proprietary SKS sustained release technology.
In an animal model used to evaluate ophthalmic compounds, sustained supratherapeutic levels of active drug were achieved in target ocular tissues at all time points in the study.
The results serve as an important validation for the company’s SKS sustained release technology which holds the promise of improving the standard of care in a number of ocular conditions.
Financial Results for the Fiscal Year ended September 30, 2016

For the year ended September 30, 2016, the Company reported a net loss of approximately $25.8 million, or ($0.82) per share, compared to a net loss of approximately $15.2 million, or ($0.54) per share in the same period of 2015.
For the year ended September 30, 2016, total operating expenses were approximately $24.6 million, consisting of $7.7 million in general and administrative expenses, $16.5 million of research and development expenses, and $1.2 million in depreciation and amortization. This compares to total operating expenses of $17.8 million in the same period of 2015, comprised of approximately $7.5 million in general and administrative expenses, $8.8 million in research and development expenses, and $1.2 million in depreciation and amortization.
At September 30, 2016, the Company had cash and cash equivalents of approximately $12.5 million. This compares to cash and equivalents of approximately $28.7 million at September 30, 2015.
On December 7, 2016, the Company sold in a public offering, an aggregate of approximately 3,885,000 shares of its common stock, together with Series A common stock purchase warrants exercisable for up to an aggregate of approximately 1,942,500 shares of common stock and Series B common stock purchase warrants exercisable for up to an aggregate of approximately 3,885,000 shares of common stock. Net proceeds from the offering were approximately $6.9 million, after deducting placement agent fees and estimated offering expenses payable but excluding the proceeds, if any, from the exercise of the Series A and Series B Warrants issued in the offering.