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Oxford BioMedica Presents Ground-Breaking Evidence of Long-Term Duration of Therapeutic Expression in Patients from its Proprietary LentiVector® Gene Delivery Platform

On May 6, 2016 Oxford BioMedica plc ("Oxford BioMedica" or "the Company") (LSE:OXB), a leading gene and cell therapy company, reported that new data has been presented from two clinical studies indicating ground-breaking long-term four-year sustained and, in one of the studies, dose-dependent gene expression with the Company’s LentiVector delivery platform (Press release, Oxford BioMedica, MAY 6, 2016, View Source [SID:1234512034]).

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On 5 May 2016, Professor Stéphane Palfi presented a poster on OXB-101, a gene therapy product for the treatment of Parkinson’s disease (PD), at the 19th Annual Meeting of the American Society of Gene and Cell Therapy (ASGCT) (Free ASGCT Whitepaper) in Washington DC, USA. In the Phase I/II study 15 advanced PD patients were treated with OXB-101 in three dose cohorts. OXB-101 demonstrated a favourable safety profile and a statistically significant improvement in motor function relative to baseline at six and 12 months post-treatment. The most recent follow-up data, presented this week, shows that the majority of patients continue to experience improvement in motor function relative to baseline over the four years since treatment. The Company has since developed OXB-102, a more potent version of OXB-101, and is planning to start a Phase I/II study in mid-2016. OXB-102 is Oxford BioMedica’s gene therapy product that utilises its proprietary LentiVector delivery platform to transfer three genes for dopamine synthesis in the striatum.

In addition, on 4 May 2016, Dr Andreas Lauer gave an oral presentation on Oxford BioMedica’s LentiVector-based treatment for neovascular age-related macular degeneration (wet AMD), at the Association for Research in Vision and Ophthalmology (ARVO) conference in Seattle, USA. Consistent with results previously announced at the ARVO conference, the new data presented demonstrates that LentiVector gene expression was dose-dependent and continued without significant decline for more than four years.

Commenting on the new emerging data, John Dawson, Chief Executive Officer of Oxford BioMedica, said: "We are very encouraged by the demonstration of long term expression and clinical benefit in patients indicated by the four-year follow-up data from these two clinical studies. We believe this is the first time gene therapy products have been directly measured in the eye and the longevity in both expression and efficacy to date reinforces the benefits of the Company’s pioneering LentiVector gene delivery platform in the treatment of chronic conditions."

– See more at: View Source#sthash.zAnILG7N.dpuf

8-K – Current report

On May 5, 2016 Mustang Bio, Inc. ("Mustang"), a Fortress Biotech (NASDAQ: FBIO) Company, reported that an oral presentation related to its MB-101 (IL13Rα2-specific CAR T cells) product candidate in development was presented by City of Hope ("COH") Investigators at the American Society of Gene and Cell Therapy 19th Annual Meeting (ASGCT) (Free ASGCT Whitepaper) at the Marriott Wardman Park Hotel in Washington, DC (Filing, 8-K, Fortress Biotech, 2016, MAY 6, 2016, View Source [SID:1234512023]).

Michael S. Weiss, Mustang Bio’s Executive Chairman, Interim Chief Executive Officer and President commented on the data, "We are very encouraged by the early safety and efficacy profile demonstrated by MB-101 (IL13Rα2-specific CAR T cells) to date. We were particularly impressed with the data presented today showing a patient treated at the first dose level who obtained an investigator designated complete response to MB-101. We believe this is the first demonstration of a response in a GBM patient utilizing CAR-T treatment. We are eager to continue the dose escalation to further assess the safety, activity and durability of MB-101 treatment at higher doses." Mr. Weiss continued, "We would like to thank the investigators at City of Hope for all of their efforts on this important research program."

The following summarizes the oral presentation today:

Phase I Study of Second Generation Chimeric Antigen Receptor–Engineered T cells Targeting IL13Rα2 for the Treatment of Glioblastoma

The Phase I study abstract that was presented showed early data evaluating the safety, feasibility and bioactivity of weekly intracranial infusions of autologous IL13Rα2-specific CAR T cells in patients with recurrent IL13Rα2+ GBM. On this study, patients are treated on a 4-week therapeutic regimen consisting of 3 weekly intracranial infusions of IL13Rα2-specific CAR T cells followed by one rest week for toxicity and disease assessment. To date, treatment of the first low dose cohort of patients has been completed demonstrating that local delivery of IL13Rα2-specific CAR T cells post-surgical resection appeared to be safe and well-tolerated, with no grade 3 or higher toxicities attributed to the therapy reported. Importantly, early evidence for antitumor activity following CAR T cell administration was observed.

One patient of particular interest presented with a recurrent multifocal GBM, including one metastatic site in the spine and extensive leptomeningeal disease. This patient was initially treated per protocol with six local infusions of IL13Rα2-specific CAR T cells into the resection cavity of the largest recurrent tumor focus in the posterior temporal-occipital region. Encouragingly, this CAR T cell injection site remained stable without evidence of disease recurrence for over 7-weeks, while other disease foci distant from the CAR T cell injection site continued to progress. This patient was then treated on a compassionate use protocol with five weekly intraventricular infusions of IL13Rα2-specific CAR T cells without any other therapeutic interventions. The investigator reported today that following treatment the patient achieved a complete response. Early clinical findings suggest that intracranial delivery of second-generation IL13Rα2-targeted CAR T cells is safe and well-tolerated, and that after adoptive transfer, CAR T cells survive and maintain activity, capable of eliciting potent antitumor responses against recurrent multifocal glioblastoma.

About Glioblastoma multiforme (GBM)
Glioblastomas (GBM) are tumors that arise from astrocytes cells that make up the supportive tissue of the brain. These tumors are usually highly malignant (cancerous) because the cells reproduce quickly and they are supported by a large network of blood vessels. GBM is the most common brain and central nervous system (CNS) malignancy, accounting for 15.1% of all primary brain tumors, and 55.1% of all gliomas. There are an estimated 12,120 new glioblastoma cases predicted in 2016 in the U.S. Malignant brain tumors are the most common cause of cancer-related deaths in adolescents and young adults aged 15-39 and the most common cancer occurring among 15-19 year olds in the U.S. (Brain Tumor Statistics. American Brain Tumor Association. December 2015). While GBM is a rare disease (2-3 cases per 100,000 person life years in the U.S. and E.U.), it is quite lethal with 5-year survival rates historically less than 10%. Chemotherapy with temozolomide and radiation are shown to extend mean survival from ~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, difficulty of the brain to repair itself and limitation to drugs 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 as it has limited expression in normal tissue but is over-expressed on the surface of the majority of GBM. CAR T cells 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.

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

ReCyte Therapeutics, a BioTime Subsidiary, Announces Peer-Reviewed Publication on Pericyte-Like Progenitor Cells

On May 6, 2016 ReCyte Therapeutics, a subsidiary of BioTime, Inc., a clinical-stage regenerative medicine company with a focus on pluripotent stem cell technology, reported the publication of a scientific paper titled, "A novel lineage restricted, pericyte-like cell line isolated from human embryonic stem cells," by Midori Greenwood-Goodwin, Jiwei Yang, Mohammad Hassanipour, and David Larocca (Press release, BioTime, MAY 6, 2016, View Source;p=RssLanding&cat=news&id=2166093 [SID:1234512020]). The article was released in the peer-reviewed online publication in Scientific Reports. The online version of the article can be found at www.nature.com/articles/srep24403.

In the article, researchers at ReCyte Therapeutics demonstrate the successful isolation of a new type of human blood vessel support cell that is involved in the formation and stabilization of blood vessels, a process known as angiogenesis. Unlike typical angiogenic support cells which are multi-talented and can turn into other types of tissues such as bone, these precursor cells, termed PC-M cells, are highly specialized to support and strengthen blood vessels.

"When you want a specific job done, its best to call a specialist for treatment," said Dr. David Larocca, Vice President of Research and Development. "That’s why we believe these novel pericyte-like cells may be an ideal source of cells for promoting new blood flow in patients suffering from ischemic vascular disease (IVD) where clogged arteries have blocked blood flow to limbs or the heart."

Left unchecked, IVD often leads to amputation or heart failure for patients that have failed, or are not candidates for surgical interventions. Thus, there is a critical unmet medical need for new angiogenic therapies. Importantly, PC-M cells are highly stable and have a high capacity to replicate under standard laboratory conditions. They therefore can be manufactured on an industrial scale needed to treat a large patient population. At ReCyte, we are currently investigating the use of PC-M cells for treating critical limb ischemia, a late stage of IVD that afflicts diabetics and the elderly.

We have also developed a PC-M cell based co-culture assay kit called VascuNet (sold by Ascendance Biotechnology, Inc.) that’s designed to be used to screen for drugs that affect human blood vessel growth and stability. This novel assay mimics the body’s own angiogenic mechanisms for growing blood vessels which involves both supporting pericytes, and the endothelial cells that line the vessel walls. This biomimetic VascuNet assay can be used to discover new anti-angiogenic cancer drugs that kill tumors by cutting off or destabilizing their blood supply. It can also be used to screen for pro-angiogenic drugs that increase blood flow for treating ischemia.

The paper, based off of BioTime/ReCyte’s extensive research and discoveries involving iPS cells, if developed, could potentially bring value to the pharmaceutical industry interested in developing cardiovascular and cancer therapies. This development ties into BioTime’s broader strategy to allow its non-core therapeutic assets to mature into successful regenerative cell therapies, for a wide variety of degenerative diseases, to help address the critical unmet medical needs of patients worldwide.

Spectrum Pharmaceuticals Highlights an Oral Presentation on Apaziquone at the 2016 Annual Meeting of the American Urological Association Education and Research Inc. (AUA) in San Diego, California, May 6-10, 2016

On May 6, 2016 Spectrum Pharmaceuticals (NasdaqGS: SPPI), a biotechnology company with fully integrated commercial and drug development operations with a primary focus in Hematology and Oncology, reported presentations of clinical data for apaziquone to be presented at an oral presentation and a moderated poster session at the American Urological Association Education and Research Inc., being held in San Diego, California, from May 6-10, 2016 (Press release, Spectrum Pharmaceuticals, MAY 6, 2016, View Source [SID:1234512013]).

For more information about the AUA Meeting and for a complete list of abstracts, please refer to the conference web site at View Source

Friday, May 6, 2016 1:00 PM-3:00 PM PT (Moderated Poster Session)

Abstract # Type Title First Author Location

MP13-07
Poster
Improved Efficacy of Adjuvant, Single Dose Intravesical Apaziquone by Timing post-Resection in Two Double
blind, Randomized, Placebo-Controlled Phase 3 Studies in Non-Muscle Invasive Bladder Cancer
Fred Witjes
Room 28 ABC

Saturday, May 7, 2016, 8:00 AM-10:00 AM PT (Podium Presentation)

Abstract # Type Title First Author Location

PD11-07
Podium
Integrated Results of Two Multicenter, Randomized, Placebo Controlled, Double Blind, Phase 3 Trials (SPI-611/612) of Single-Dose Intravesical Apaziquone Immediately Following Resection in Patients with Non-Muscle Invasive Bladder Cancer

Myriad to Present Three New Studies at the AUA Annual Meeting

On May 06, 2016 Myriad Genetics, Inc. (NASDAQ:MYGN), a leader in molecular diagnostics and personalized medicine, reported that results from three studies will be featured at the American Urological Association annual meeting, which will take place May 6-10 in San Diego, Calif (Press release, Myriad Genetics, MAY 6, 2016, View Source [SID:1234512009]). Poster discussions include new data for the Prolaris test in patients with low-risk prostate cancer, as well as investigational molecular diagnostic tests for renal and bladder cancer.

"Prolaris is the leading prognostic genetic test for patients with prostate cancer and is the only such test that predicts the 10-year risk of real oncologic outcomes including death, metastases and recurrence. The evidence in favor of genetic testing is expanding, and we’re excited to present a new analysis at AUA that further confirms the strong prognostic power of Prolaris in men with low-risk localized prostate cancer," said Michael Brawer, senior vice president of Medical Affairs, Myriad Genetic Laboratories. "We also are presenting new data for our investigational renal and bladder cancer tests, which further underscore Myriad’s commitment to developing pioneering molecular diagnostic tests for other urologic diseases."

Results of the studies to be presented are described below and abstracts are now available at: www.aua2016.org/abstracts/. Follow Myriad on Twitter via @MyriadGenetics to stay informed about news and updates from the Company.

Highlighted Presentations

Title: The CCP score provides significant prognostic information in Gleason score <6 patients.
Date: Friday, May 6, 2016: 8:00—10:00 a.m. PT.
Location: Poster MP2.
Presenter: Jay Bishoff, M.D., Intermountain Urological Institute.
This meta-analysis of five studies evaluated the ability of the Prolaris test (CCP score) to predict oncologic outcomes (i.e., recurrence or death) in 440 patients with low-risk localized prostate cancer, which was defined as a Gleason score of 6 or less. The results showed that the Prolaris test is a significant predictor of oncologic outcomes in patients with low-risk disease (HR 1.5; p<0.009). Prolaris also was a better independent predictor of outcomes than traditional clinical features as measured by CAPRA (Cancer of the Prostate Risk Assessment; HR 1.27; p<0.03). When the Prolaris and CAPRA scores were assessed together, the combined clinical risk (CCR) score provided even greater predictive power (HR 1.83; p<0.0014). In this study, Prolaris was a strong predictor of the 10-year risk of oncologic outcomes in patients with localized prostate cancer and a Gleason score of 6 or less.

Title: A study to evaluate the prognostic and predictive utility of CCP and HRD assays and genetic sequencing in patients undergoing neoadjuvant chemotherapy in bladder cancer.
Date: Sunday, May 8, 2016: 1:00—3:00 p.m. PT.
Location: Poster MP49.
Presenter: Hristos Kaimakliotis, M.D., Indiana University.
This exploratory study evaluated three molecular assays to determine if they were able to predict response to neoadjuvant chemotherapy with cisplatin in patients with urothelial bladder cancer (UBC). The assays included 1) a cell cycle progression score, 2) the homologous recombination deficiency (HRD) score, and 3) genetic sequencing of a set of 80 genes associated with UBC. The results showed that RB1 mutations were associated with response to cisplatin neoadjuvant chemotherapy, and the predictive ability was improved by the addition of either the CCP or HRD scores. Additionally, HRD could be used to predict risk of disease recurrence in patients after neoadjuvant chemotherapy followed by cystectomy. If validated, these tests may help identify chemo-responsive patients.

Title: Prognostic utility of a multi-gene signature (the cell cycle proliferation score) in patients with renal cell carcinoma (RCC) after radical nephrectomy.
Date: Monday, May 9, 2016: 3:30—5:30 p.m. PT.
Location: Poster MP78.
Presenter: Adam Feldman, M.D., Massachusetts General Hospital.
The objective of this study was to assess the ability of the Myriad myPlan Renal Cancer cell cycle progression test to predict long-term oncologic outcomes in patients with surgically-resected renal cell carcinoma (RCC). Outcomes were defined as disease recurrence (local or metastatic) or disease-specific survival (DSS). Patient data were censored at five-years of follow-up. In the training cohort (N= 305), the myPlan Renal Cancer test was a significant prognostic predictor for recurrence (HR: 1.74; p = 0.02) and DSS (HR: 2.59; p< 0.001) after adjusting for clinical variables. The validation cohort (N=262) demonstrated a consistent and significant prediction of recurrence and DSS, with the strongest association being for DSS (HR: 2.2; p < 0.001) after adjusting for clinical variables. Based on these data, the myPlan Renal Cancer test appears to be a significant and independent predictor of key long-term oncologic outcomes in patients who have undergone nephrectomy for RCC, providing prognostic information beyond what is available from clinical parameters. Additional studies are underway to evaluate the utility of the score when derived from diagnostic biopsy.

About Prolaris
Prolaris is a novel 46-gene RNA-expression test that directly measures tumor cell growth characteristics for stratifying the risk of disease-specific mortality in patients with prostate cancer. Prolaris provides a quantitative measure of the RNA expression levels of genes involved in the progression of tumor growth. Low gene expression is associated with a low risk of disease-specific mortality in men who may be candidates for active surveillance and high gene expression is associated with a higher risk of disease-specific mortality in patients who may benefit from additional therapy. For more information visit: www.prolaris.com.

About myChoice HRD
Myriad’s myChoice HRD is the first homologous recombination deficiency test that can detect when a tumor has lost the ability to repair double-stranded DNA breaks, resulting in increased susceptibility to DNA-damaging drugs such as platinum drugs or PARP inhibitors. High myChoice HRD scores reflective of DNA repair deficiencies are prevalent in all breast cancer subtypes, ovarian and most other major cancers. In previously published data, Myriad showed that the myChoice HRD test predicted drug response to platinum therapy in certain patients with triple-negative breast and ovarian cancers. It is estimated that 1.8 million people in the United States and Europe who are diagnosed with cancers annually may be candidates for treatment with DNA-damaging agents. For more information visit: www.myriad.com.

About Myriad myPlan Renal Cancer
Myriad myPlan Renal Cancer is a molecular prognostic test that measures the expression levels of cell cycle progression genes to provide an accurate assessment of cancer aggressiveness in patients with renal cell carcinoma. For more information visit: View Source