On June 11, 2015 BIND Therapeutics, a subsidiary of Navidea Biopharmaceuticals reported they have entered into a research collaboration to engineer Accurins with the Manocept targeting platform that enables selective, efficient binding to CD206 positive disease-associated macrophages (Press release, Navidea Biopharmaceuticals, JUN 11, 2015, View Source;p=RssLanding&cat=news&id=2058494 [SID:1234505428]). Upon achievement of proof-of-concept, the companies anticipate expanding the collaboration to develop Manocept-linked Accurins as a novel, potent approach to impact the tumor microenvironment which, in many forms of cancer, is a barrier to immune effector cells.

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"This collaboration represents a potentially significant advance in the evolution of our platform as we develop Accurins with novel targeting ligands," said Andrew Hirsch, president and chief executive officer of BIND Therapeutics. "The modular nature of our platform offers multiple therapeutic possibilities, and our collaboration with Macrophage Therapeutics may enable the development of Accurins that target activated macrophages, which in cancer, help create an immunosuppressive microenvironment. We believe the clinically validated Manocept platform, with its unique ability to seek out activated macrophages, fits into our vision to engineer Accurins that have a profound impact on the treatment of diseases, including our current focus in cancer."

Disease-associated macrophages generally play a pro-tumoral role and are immunosuppressive, preventing the immune system from mounting an attack on tumor cells. Based on the expression of CD206 mannose receptors on disease-associated macrophages, BIND and Macrophage plan to conduct joint research to develop a CD206 targeted Accurin nanoparticle that is capable of concentrating various therapeutic payloads to the tumor microenvironment.

"We are pleased to work with BIND Therapeutics to explore the therapeutic potential of our two complementary technology platforms," said Michael M. Goldberg, M.D., CEO of Macrophage Therapeutics and Director of Navidea. "The Manocept platform is the basis for the FDA-approved CD206 targeted sentinel lymph node detection agent, Lymphoseek (technetium Tc 99m tilmanocept) injection. Coupled with BIND’s specifically engineered Accurins that concentrate therapeutic payloads to extracellular and intracellular compartments, with a tunable controlled-release profile, we are optimistic that we can create a wide range of therapeutic applications."

"It is well-established that macrophages play an important role in many disease states but it has proven difficult to selectively target and alter macrophages that play a key role in disease progression," said Hagop Youssoufian, M.Sc., M.D., chief medical officer at BIND Therapeutics. "By coupling Accurins with Macrophage’s well-credentialed CD206 targeting ligand, we may be able to treat macrophage-mediated diseases through increased uptake, and concentration, of targeted therapeutic payloads in the tumor microenvironment. BIND’s Medicinal Nanoengineering platform is able to combine multiple molecular components into a targeted, long-circulating Accurin. An Accurin nanoparticle that binds to CD206 positive macrophages could be a valuable asset in the armament against multiple cancers and disease states."

"The collaboration furthers our vision to develop therapeutic applications of the Manocept platform through strategic partnerships," said Rick Gonzalez, president and CEO of Navidea. "In collaborating with BIND, we will be able to leverage their accomplished R&D team who has strong track record for advancing targeted nanoparticles from concept into the clinic."

About Accurins

Accurins, a new class of targeted therapeutics developed using BIND’s Medicinal Nanoengineering platform, are nanoparticles engineered to have a profound impact on the treatment of disease. The elegant and novel design of Accurins allow for prolonged circulation, controlled and tunable release and selective targeting of a therapeutic payload to diseased tissue or cells while avoiding immune surveillance detection and systemic toxicities.

Accurins can be engineered for multiple therapeutic applications and have the potential to integrate numerous payloads, including highly potent drugs with mechanism-based toxicities that limit therapeutic benefit, DNA, RNA, proteins and immunotherapy agents. This attribute enables Accurins to target multiple diseases, including cancer, inflammatory, vascular, and infectious disease.

About Manocept CD206 Targeting Platform for Therapeutics Development

Manocept CD206 Targeting Platform is a proprietary mannose-containing, receptor-directed technology platform designed to engineer novel, synthetic receptor targeted imaging agents and therapeutics for cancer and other diseases. Manocept’s unique structural and molecular properties enable the design of novel immuno-constructs that selectively target and bind to CD206 (mannose receptor) and other C-type Lectins found on activated, disease-associated macrophages and tumor associated macrophages (TAMs). The Manocept CD206 Targeting Platform provides a novel and valuable approach to the design of drug molecules targeting CD206 disease-associated macrophages for therapeutic purposes.

About Lymphoseek

Lymphoseek (technetium Tc 99m tilmanocept) injection is the first and only FDA-approved receptor-targeted lymphatic mapping agent. It is a novel, receptor-targeted, small-molecule radiopharmaceutical used in the evaluation of lymphatic basins that may have cancer involvement in patients. Lymphoseek is designed for the precise identification of lymph nodes that drain from a primary tumor, which have the highest probability of harboring cancer. Lymphoseek is approved by the U.S. Food and Drug Administration (FDA) for use in solid tumor cancers where lymphatic mapping is a component of surgical management and for guiding sentinel lymph node biopsy in patients with clinically node negative breast cancer, melanoma or squamous cell carcinoma of the oral cavity. Lymphoseek has also received European approval in imaging and intraoperative detection of sentinel lymph nodes in patients with melanoma, breast cancer or localized squamous cell carcinoma of the oral cavity.

Accurate diagnostic evaluation of cancer is critical, as it guides therapy decisions and determines patient prognosis and risk of recurrence. Overall in the U.S., solid tumor cancers may represent up to 1.2 million cases per year. The sentinel node label in the U.S. and Europe may address approximately 235,000 new cases of breast cancer, 76,000 new cases of melanoma and 45,000 new cases of head and neck/oral cancer in the U.S., and approximately 367,000 new cases of breast cancer, 83,000 new cases of melanoma and 55,000 new cases of head and neck/oral cancer diagnosed in Europe annually.

Lymphoseek Indication and Important Safety Information

Lymphoseek is a radioactive diagnostic agent indicated with or without scintigraphic imaging for:

Lymphatic mapping using a handheld gamma counter to locate lymph nodes draining a primary tumor site in patients with solid tumors for which this procedure is a component of intraoperative management.
Guiding sentinel lymph node biopsy using a handheld gamma counter in patients with clinically node negative squamous cell carcinoma of the oral cavity, breast cancer or melanoma.
Important Safety Information

In clinical trials with Lymphoseek, no serious hypersensitivity reactions were reported, however Lymphoseek may pose a risk of such reactions due to its chemical similarity to dextran. Serious hypersensitivity reactions have been associated with dextran and modified forms of dextran (such as iron dextran drugs).

Prior to the administration of Lymphoseek, patients should be asked about previous hypersensitivity reactions to drugs, in particular dextran and modified forms of dextran. Resuscitation equipment and trained personnel should be available at the time of Lymphoseek administration, and patients observed for signs or symptoms of hypersensitivity following injection.

Any radiation-emitting product may increase the risk for cancer. Adhere to dose recommendations and ensure safe handling to minimize the risk for excessive radiation exposure to patients or health care workers.

In clinical trials, no patients experienced serious adverse reactions and the most common adverse reactions were injection site irritation and/or pain (<1%).

On June 10, 2015 Intrexon Corporation (NYSE: XON), a leader in synthetic biology, and Oragenics (NYSE:MKT – OGEN) reported a new Exclusive Channel Collaboration (ECC) to pursue development of biotherapeutics for oral mucositis (OM) and other diseases and conditions of the oral cavity, throat, and esophagus, including clinical advancement of the ActoBiotic AG013 for the treatment of OM (Press release, Intrexon, JUN 10, 2015, View Source [SID:1234514823]). OM results in the painful inflammation and ulceration of the membranes lining the oral cavity, throat, and esophagus and is among the most frequently reported adverse events associated with cancer therapy affecting up to 500,000 patients annually. At present there is no drug approved to prevent the condition broadly and therapies are primarily palliative, alleviating symptoms without addressing the underlying pathology, resulting in a significant unmet medical need.

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"We are eager to advance therapeutic programs through the established clinical foundations of the ActoBiotics platform, and moving forward in the clinic with AG013 is a natural fit for our focus on the treatment of oral cavity diseases with innovative biopharmaceuticals," said Frederick Telling, Ph.D., Chairman of the Board of Oragenics. "Work continues under our current collaboration with Intrexon centered on the development of a novel class of antibiotics known as lantibiotics, and we are excited to build on this relationship in the field of oral health to realize the promise of microbial approaches in the generation of efficacious new medicines."

"I am pleased that this new collaboration provides an opportunity for continued development of AG013 as an intervention for oral mucositis," said Stephen T. Sonis, DMD, DMSc, Senior Surgeon, Divisions of Oral Medicine, Brigham and Women’s Hospital and the Dana-Farber Cancer Institute. "AG013’s successful attenuation of chemotherapy-induced oral mucositis in the Phase 1B trial suggests that this innovative delivery platform may offer a new approach to the treatment of this important unmet clinical need."

Through the molecular engineering of food-grade microbes (Lactococcus lactis), biologically-contained ActoBiotics allow for in situ expression and secretion of novel biotherapeutic proteins and peptides. AG013 is formulated as a convenient oral rinsing solution and designed to deliver the therapeutic molecule Trefoil Factor 1 (TFF1) to the mucosal tissues in the oral cavity. TFFs are a class of peptides that are involved in protection of the gastrointestinal tissues against mucosal damage and have an important role in subsequent repair.

A phase 1B clinical trial with AG013 in 25 cancer patients with OM across 5 cancer referral centers showed that AG013 was safe and well tolerated. Data published in the journal Cancer showed a 35% reduction of the duration of ulcerative OM in the AG013-treated patients versus the placebo-treated patients. Furthermore, close to 30% of the patients treated with AG013 were full responders while all placebo-treated patients developed ulcerative OM. Additionally, a phase 1 pharmacokinetic (PK) study in 10 healthy volunteers showed that live AG013 bacteria adhere to the buccal mucosa and actively secrete protein locally, resulting in homogeneous exposure to the entire mucosal surface up to 24 hours after administration of a rinse. AG013 has already been granted Orphan Drug status in the European Union and has potential eligibility for Biologic License Application exclusivity as well as Fast Track designation with the United States Food and Drug Administration.

Under the terms of the agreement, Oragenics will have access to Intrexon’s technologies and expertise to develop products for the treatment of oral mucositis or products containing genetically modified Lactococcus lactis expressing trefoil factors in the oral cavity, throat, and esophagus for a technology access fee and will reimburse Intrexon for the research and development costs. The agreement also provides for commercial and regulatory milestone payments to Intrexon, as well as a low double-digit percentage royalty based on the net sales from collaboration products.

"AG013 represents a promising product from a truly innovative platform for the prevention of oral mucositis in cancer patients," commented Gregory Frost, Ph.D., Senior Vice President and Head of Intrexon’s Health Sector. "We are very pleased with the expanded collaboration with Oragenics, especially given their unique experience in the field of oral health using novel approaches. This ECC will further the clinical development of AG013 in the hope of providing cancer patients with a much needed adjunctive therapy for oral mucositis, a challenging side effect that can become a treatment-limiting toxicity for effective cancer therapy."

On June 10, 2015 DelMar Pharmaceuticals reported that it will be presenting at the BIO International Convention being held June 15-18, 2015, in Philadelphia, PA (Press release, DelMar Pharmaceuticals, JUN 10, 2015, View Source [SID:1234505389]).

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Jeffrey Bacha, DelMar’s president and CEO, will present on Wednesday, June 17, 2015, at 10:15 a.m. EDT, in Theater 4 of the Pennsylvania Convention Center. Mr. Bacha will provide an update on the Company’s drug development programs with its lead product candidate VAL-083 (dianhydrogalactitol), including DelMar’s ongoing Phase 1/2 trial in refractory glioblastoma multiforme (GBM), the most common and deadly form of brain cancer, and upcoming clinical development plans in non-small cell lung cancer (NSCLC).

About the BIO International Convention

The BIO International Convention is considered one of the world’s largest, most influential biotech meetings and regularly attracts 15,000 of the most powerful biotech and pharma players from 65 countries, offering powerful business partnering, networking and education that go far beyond professional development. DelMar management will be available during the conference for meetings with potential drug development and commercialization partners from the biopharmaceutical industry. For more information, please visit View Source

About VAL-083

VAL-083 is a "first-in-class", small-molecule chemotherapeutic. In more than 40 Phase 1 and 2 clinical studies sponsored by the U.S. National Cancer Institutes, VAL-083 demonstrated safety and efficacy in treating a number of cancers including lung, brain, cervical, ovarian tumors and leukemia. VAL-083 is approved in China for the treatment of chronic myelogenous leukemia and lung cancer and has received orphan drug designation in Europe and the U.S. for the treatment of gliomas.

As a potential treatment for glioblastoma, VAL-083’s mechanism of action appears to be unaffected by the expression of MGMT, a DNA repair enzyme that causes chemotherapy resistance to front-line treatment with Temodar (temozolomide).

DelMar is currently studying VAL-083 in a multi-center Phase I/II clinical trial for patients with refractory glioblastoma multiforme (GBM) in accordance with the protocol that has been filed with the U.S. Food and Drug Administration (FDA). Eligible GBM patients must have failed both Avastin (bevacizumab) and Temodar (temozolomide) unless either of these therapies was contraindicated. (ClinicalTrials.gov Identifier NCT01478178).

The four current sites for the VAL-083 clinical trial include: The University of California, San Francisco (UCSF); The Mayo Clinic, Rochester MN; The Sarah Cannon Cancer Research Institute (SCRI), Nashville TN; and the SCRI affiliate site at Florida Cancer Specialists in Sarasota FL. DelMar anticipates opening additional clinical sites as the trial progresses. Further information on this clinical trial can be found on the company’s website at www.delmarpharma.com.

On June 10, 2015 OncoGenex Pharmaceuticals reported that the U.S. Food and Drug Administration (FDA) has agreed to the Company’s proposed amendment to the Phase 3 AFFINITY protocol and statistical analysis plan (Press release, OncoGenex Pharmaceuticals, JUN 10, 2015, View Source [SID:1234505390]). The amendment includes the addition of a co-primary endpoint designed to prospectively evaluate the survival benefit of custirsen in men who are at increased risk for poor outcomes when treated with cabazitaxel for metastatic castrate-resistant prostate cancer (CRPC).

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"There are limited effective treatment options for men with metastatic CRPC who have risk factors for poor outcomes and who fall into a poor prognosis category. Recent findings from the SYNERGY trial showed a significant survival benefit in this group of patients," said Cindy Jacobs, PhD, MD, Chief Medical Officer and Executive Vice President of OncoGenex. "We have applied this key insight from the SYNERGY trial to the AFFINITY protocol to better evaluate this vulnerable subpopulation of men who have poor prognosis and shorter survival time."

The FDA is in agreement with plans for prospectively defining a poor prognostic subpopulation in the Phase 3 AFFINITY trial. OncoGenex, in collaboration with study investigators, has defined a simple 5-criteria characterization for poor prognosis in prostate cancer based on the Phase 3 SYNERGY trial, which includes: poor performance status, elevated prostate specific antigen (PSA), elevated lactate dehyrdogenase (LDH), decreased hemoglobin, and the presence of liver metastasis. Patients with poor prognosis will be identified as having 2 or more of these 5 well-recognized high-risk criteria. The proposed change for AFFINITY is also consistent with custirsen’s mechanism of action, since custirsen was designed to address treatment resistance which may be more prevalent in this subpopulation.

In the revised statistical analysis plan for the AFFINITY trial, the hypothesized hazard ratio (HR) for the poor prognosis subpopulation is specified to be 0.69 with the critical HR ≤ 0.778. The hypothesized HR for the intent-to-treat patients (ITT population) remains unchanged as 0.75 with the critical HR ≤ 0.820.

Timing for the final analysis of the poor prognosis subpopulation is projected to occur by the end of 2015, while the final analysis for the ITT population is projected to occur in the second half of 2016. FDA and OncoGenex have further agreed that an interim analysis will occur for the ITT population when the final analysis for the poor prognosis subpopulation occurs. This interim analysis will have both futility and early efficacy criteria defined for the ITT population. If the earlier final analysis on the poor prognostic subpopulation shows a survival benefit for custirsen, OncoGenex could initiate a regulatory submission. The entire trial could also be stopped early due to efficacy based on the interim assessment for the ITT population by the Independent Data Monitoring Committee (IDMC).

"Findings from the SYNERGY trial recently presented at ASCO (Free ASCO Whitepaper) have provided important insight into the patient population in whom custirsen treatment is most relevant," said Scott Cormack, President and CEO of OncoGenex. "We are pleased that the FDA has agreed with our amendment and look forward to announcing top-line results at the end of this year and in 2016."

OncoGenex has also initiated a review with the European Medicines Agency (EMA) for the proposed amendment to the Phase 3 AFFINITY protocol and statistical analysis plan, and expects to have this completed in the second half of 2015.

A retrospective analysis of data from the Phase 3 SYNERGY trial recently presented at the 51st Annual Meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) showed a benefit with custirsen therapy when added to first-line docetaxel chemotherapy in men with metastatic CRPC who had a poor prognosis. The analysis showed that over 40 percent of men in the trial had at least 2 of the 5 common risk factors for poor prognosis as stated above. In these men, the analysis found a 27 percent lower risk of death when custirsen was used in combination with first-line docetaxel compared to docetaxel alone.

AFFINITY is being conducted at 95 global clinical trial sites and earlier this year, the IDMC recommended the trial continue following the completion of an interim futility analysis. The trial is fully accrued, and the protocol amendment does not affect the conduct of the study.

On June 10, 2015 Agios Pharmaceuticals reported that the U.S. Food and Drug Administration (FDA) has granted the company orphan drug designation for AG-120 for treatment of patients with acute myelogenous leukemia (AML) (Press release, Agios Pharmaceuticals, JUN 10, 2015, View Source;p=RssLanding&cat=news&id=2058334 [SID:1234505391]). AG-120 is an oral, first-in-class IDH1 mutant inhibitor being evaluated in a Phase 1 clinical trial in patients with advanced hematologic malignancies that carry an IDH1 mutation.

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The FDA’s Office of Orphan Drug Products grants orphan status to support development of medicines for underserved patient populations, or rare disorders, that affect fewer than 200,000 people in the U.S. Orphan drug designation provides to Agios certain benefits, including market exclusivity upon regulatory approval if received, exemption of FDA application fees and tax credits for qualified clinical trials.

"Receiving orphan drug designation for AG-120 is an important milestone as we continue to move this program to late-stage development," said Chris Bowden, M.D. chief medical officer of Agios. "We are pleased with the progress we are making in the clinic and look forward to presenting new data from our ongoing Phase 1 study of AG-120 at the Congress of the European Hematology Association (EHA) (Free EHA Whitepaper) later this week. We believe that AG-120, which is on track to initiate multiple expansion cohorts in the next month, has the potential to play a significant role in shifting the treatment paradigm for IDH1-mutant positive hematologic cancers from the conventional chemotherapy approach."

AML, a cancer of blood and bone marrow characterized by rapid disease progression, is the most common acute leukemia in adults. Undifferentiated blast cells proliferate in the bone marrow rather than mature into normal blood cells. AML incidence significantly increases with age, and according to the American Cancer Society the median age is 66. Less than 10 percent of U.S. patients are eligible for bone marrow transplant, and the vast majority of patients do not respond to chemotherapy and progress to relapsed/refractory AML. The five-year survival rate for AML is approximately 20 to 25 percent. IDH1 mutations are present in about 6 to 10 percent of AML cases.