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8-K – Current report

On May 27, 2014 Hemispherx Biopharma reported that on May 13, 2014, the United States Patent Office issued U.S. Patent 8,722,874 titled "Double-Stranded Ribonucleic Acids with Rugged Physiochemical Structure and Highly Specific Biologic Activity" to inventors Carter, et al. and assignee Hemispherx Biopharma, Inc (Filing 8-K , Hemispherx Biopharma, MAY 27, 2014, View Source [SID:1234500555]). The patent claims a novel form of rugged dsRNA. Rugged dsRNA are nucleic acids with a unique composition and physical characteristic identified with high specificity of binding to Toll-Like Receptor 3 (TLR3), thereby conveying an important range of therapeutic opportunities. The newly discovered form of dsRNA has increased bioactivity and binding affinity to the TLR 3 receptor because of its reduced tendency to form branched dsRNA which can inhibit receptor binding. Pharmaceutical formulations containing the newly discovered nucleic acid as active ingredients and methods of treatment, with those formulations are also described in the issued patent.
The original U.S. composition-of-matter patent on Ampligen was issued to Johns Hopkins University in the early 1970’s, published in the Journal of Molecular Biology, and thereafter licensed to Hemispherx Biopharma, Inc. exclusively. Upon expiration of the original patent, Hemispherx relied on a continued research program and sizable portfolio of subsequently issued patents to maintain a degree of proprietary protection for novel compositions and treatment methods based on Ampligen technology. The issuance of U.S. Patent 8,722,874 will help ensure that Hemispherx Biopharma retains patent protection for novel formulations of Ampligen products until at least 2029. The current Ampligen formulations, as a mixture of RNA of different sizes and variable binding affinities to cell receptors, affords a unique array of potential disease fighting properties through antiviral and immunomodulatory mechanisms. The newly issued patent discusses how dsRNAs acting thru TLR3 receptor activation are potent antiviral compounds and anticancer agents and through secondary immunomodulators that can enhance the bioactivity of vaccines and treat autoimmune diseases.
The significant extension of proprietary longevity via the new composition-of-matter patent may favorably affect patent longevity of Ampligen in approximately 20-25 countries.

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Bristol-Myers Squibb and CytomX Therapeutics Announce Worldwide Collaboration to Develop Probody™ Therapeutics Against Multiple Immuno-Oncology Targets

On May 27, 2014 Bristol-Myers Squibb and CytomX reported that the companies have signed a worldwide research collaboration and license agreement to discover, develop and commercialize novel therapies against multiple immuno-oncology targets using CytomX’s proprietary Probody Platform (Press release Bristol-Myers Squibb, MAY 27, 2014, View Source [SID:1234500553]).
Probodies are monoclonal antibodies that are selectively activated within the cancer microenvironment, focusing the activity of therapeutic antibodies to tumors and sparing healthy tissue. The unique selectivity of Probodies expands the therapeutic window for both validated and novel targets, and has the potential to create multiple new classes of safer and more effective therapies.
Under the terms of the agreement, CytomX will grant Bristol-Myers Squibb exclusive worldwide rights to develop and commercialize Probodies for up to four oncology targets including CTLA-4, a clinically validated immune inhibitory checkpoint receptor. Bristol-Myers Squibb will have certain additional rights to substitute up to two collaboration targets. Bristol-Myers Squibb will make an upfront payment of $50 million to CytomX and provide research funding over the course of the research term. CytomX will also be eligible to receive additional preclinical payments and up to $298 million in future development, regulatory and sales milestone payments for each collaboration target, as well as tiered mid-single-digit rising to low-double-digit royalty payments on net sales of each product commercialized by Bristol-Myers Squibb.

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Celator(R) Pharmaceuticals Announces Publication of Positive Phase 2 Data With CPX-351 in Acute Myeloid Leukemia Patients

On May 27, 2014 Celator Pharmaceuticals reported the publication of the Phase 2 study evaluating CPX-351 in newly diagnosed older patients with acute myeloid leukemia (AML) in Blood, the official journal of the American Society of Hematology (ASH) (Free ASH Whitepaper) (Press release Celator Pharmaceuticals, MAY 27, 2014, View Source [SID:1234500554] & Blood. 2014 May 22;123(21):3239-46. doi: 10.1182/blood-2013-12-540971. Epub 2014 Mar 31. View Source). The study manuscript entitled “Phase 2 trial of CPX-351, a fixed 5:1 molar ratio of cytarabine/daunorubicin, vs cytarabine/daunorubicin in older adults with untreated AML” appears in the May 22, 2014 issue.
These data, along with results from the Phase 2 study of CPX-351 in patients with AML in first relapse, support Celator’s currently-enrolling Phase 3 study of CPX-351 as a first-line therapy in older patients with high-risk (secondary) AML, which is being conducted in partnership with The Leukemia & Lymphoma Society.
This randomized, controlled, Phase 2 study evaluated 126 patients, aged 60-75 years, from 18 clinical centers in the U.S. and Canada, with newly diagnosed, pathologically confirmed AML. Patients were randomized 2:1 to receive first-line CPX-351 (100 u/m2; days 1, 3, and 5 by 90 minute infusion) or the 7+3 regimen (cytarabine 100 mg/m2/day by continuous infusion for 7 days and daunorubicin 60 mg/m2 on days 1, 2, and 3). The primary endpoint for the study was complete response (CR + CRi) and secondary endpoints included CR+CRi duration, event-free survival and overall survival.
Results showed that CPX-351 treatment was associated with higher complete response rate (66.7% vs. 51.2%; P = 0.07), prolonged event-free survival (median 6.5 vs. 2.0 months) and overall survival (median 14.7 vs. 12.9 months). Ten patients with persistent AML after treatment with 7+3 crossed over to receive CPX-351 as salvage therapy with four achieving response (3 CR + 1 CRi). All four responders survived more than one year and this potentially confounds interpretation of the overall survival data.
A planned analysis of secondary AML patients (patients with a prior antecedent hematologic disorder or history of prior cytotoxic treatment) showed an improved response rate (57.6% vs 31.6%, P=0.06), prolonged event-free survival (median 4.5 vs. 1.3 months, HR=0.59, P=0.08) as well as overall survival (median 12.1 vs. 6.1 months, HR=0.46, P=0.01). The overall survival benefit in this population was statistically significant.
Treatment with CPX-351 was associated with well-characterized and manageable adverse events. Recovery from cytopenias was longer following CPX-351 (median days to ANC ≥1000: 36 vs. 32; Platelets > 100K: 37 vs. 28) with more grade 3-4 infections but without an increase in infection-related deaths (3.5% vs. 7.3%) or 60-day mortality (4.7% vs. 14.6%), indicating acceptable safety.

Bristol-Myers Squibb and Incyte Enter Clinical Collaboration Agreement to Evaluate Combination Regimen of Two Novel Immunotherapies

On May 27, 2014 Bristol-Myers Squibb and Incyte reported the establishment of a clinical trial collaboration to evaluate the safety, tolerability and preliminary efficacy of a combination regimen of Bristol-Myers Squibb’s investigational PD-1 immune checkpoint inhibitor, nivolumab, and Incyte’s oral indoleamine dioxygenase-1 (IDO1) inhibitor, INCB24360, in a Phase I/II study (Press release Bristol-Myers Squibb, MAY 27, 2014, View Source [SID:1234500552]). Multiple tumor types will be explored in the study, which could potentially include melanoma, non-small cell lung (NSCLC), ovarian, colorectal (CRC), squamous cell carcinoma of the head and neck (SCCHN) and diffuse large B-cell lymphoma (DLBCL).
Nivolumab and INCB24360 are part of a new class of cancer treatments known as immunotherapies that are designed to harness the body’s own immune system in fighting cancer. Nivolumab and INCB24360 target distinct regulatory components of the immune system, and there is preclinical evidence suggesting that the combination of these two agents may lead to an enhanced anti-tumor immune response compared to either agent alone.
The study, which is expected to begin in the fourth quarter of 2014, will be co-funded by the companies and conducted by Incyte. Additional details of the collaboration were not disclosed.

Advaxis’s HER2 Immunotherapy Candidate Receives Orphan Drug Designation for Treatment of Osteosarcoma

On May 27, 2014 Advaxis reported that it has been granted Orphan Drug Designation (ODD) from the U.S. Food and Drug Administration (FDA) Office of Orphan Products Development (OOPD) for ADXS-cHER2 for the treatment of osteosarcoma (Press release Advaxis, MAY 27, 2014, View Source [SID:1234500551]).
ADXS-cHER2 is an immunotherapy under investigation for targeting the HER2 receptor, which is overexpressed in certain solid-tumor cancers, including bone cancer and breast cancer. Based on strong pre-clinical and canine osteosarcoma clinical data, Advaxis is planning to initiate a clinical development program with ADXS-cHER2 in pediatric patients with osteosarcoma. Pediatric osteosarcoma affects about 400 children and teens in the U.S. every year, representing a small but significant unmet medical need that has seen little therapeutic advancement in decades. Both veterinary and human osteosarcoma specialists consider canine osteosarcoma to be the most analogous disease to human osteosarcoma.