On July 2, 2015 Macrophage Therapeutics, a subsidiary of Navidea Biopharmaceuticals reported that preclinical results in Kaposi’s Sarcoma (KS) demonstrated that a cytotoxic drug, doxorubicin, linked to Manocept was targeted to and dose-dependently taken up in CD206+ KS tumor cells and tumor associated macrophages (TAMs) and caused apoptotic death of the KS tumor cells and TAMs (Press release, Navidea Biopharmaceuticals, JUL 2, 2015, View Source;p=RssLanding&cat=news&id=2064425 [SID:1234506022]). The results are being presented at the 18th International Workshop on Kaposi’s Sarcoma Herpesvirus (KSHV) and Related Agents in Hollywood, Florida by Michael S. McGrath, M.D., Ph.D., Professor, Departments of Laboratory Medicine, Pathology, and Medicine at the University of California, San Francisco (UCSF). The study also shows that Cy3-Manocept and a Cy3-Manocept-doxorubicin conjugate quantitatively permitted the evaluation of tumor burden, tissue uptake of Manocept and tumor response to therapy in vitro and ex vivo, supporting the potential for the Manocept platform to be used not only diagnostically but as a precision targeted molecule to deliver payloads to tumor sites throughout the body.

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"Advances in the treatment of cancer such as the recently approved PD1 and PDL1 inhibitors demonstrate the benefit of disrupting the communication signals between tumors and immune cells," said Frederick O. Cope, Ph.D., FACN, Chief Scientific Officer of Macrophage Therapeutics. "Based on the role tumor associated macrophages are thought to play in the progression of cancer, there exists a strong rationale that targeting CD206 represents a therapeutic pathway that is highly likely to exist across tumor types, and which reverses the immunosuppressive effects of cancer cells."

"In my experience, the impressive loss of TAMs demonstrated in these Manocept studies is unique and potentially extremely relevant clinically," said Dr. McGrath. "The results from data in primary human KS tissue, which provides the closest experimental model to human patients, showed not only selective killing of only CD206+ KS tumor cells and macrophages, but demonstrated through a biomarker that the Manocept conjugate induced programmed cell death in tumor cells and exhibited unprecedented anti-HIV activity which could eventually address a broad unmet need for patients with Kaposi’s sarcoma and other tumor types."

The preclinical studies included use of Human peripheral blood mononuclear cells (PBMCs) to measure the time course of Manocept uptake in CD206+ macrophages. Flow cytometry studies identifying CD206+ cells allowed quantitation of the amount of Cy3-Manocept bound to and internalized into the CD206+ cells and also verified Cy3-Manocept-doxorubicin internalization. Confocal microscopy was used with KS biopsies that were cultured overnight with Cy3-Manocept or Cy3-Manocept-doxorubicin and showed that all cells within the KS tissue including macrophages and spindle cells were CD206+ and incorporated the Cy3-Manocept with and without doxorubicin. In KS organ cultures, immunofluorescence assays for the detection of antibodies against latent nuclear antigen (IFA-LANA) and Annexin V were performed. Inhibition studies showed Cy3-Manocept-doxorubicin exhibited anti-HIV activity in HIV infected macrophage culture. In summary, the data presented include evidence that:

KS tissue based cells take up Cy3-Manocept or Cy3-Manocept-doxorubicin into both KS tumor cells and TAMs.

Manocept conjugate uptake is dose and time dependent in CD206+ macrophages

Cy3-Manocept and Cy3-Manocept-doxorubicin bind to CD206 positive macrophages equivalently indicating that the linkage of a drug conjugate did not lessen the CD206 binding ability

Manocept-doxorubicin killed CD206 expressing macrophages. After 24 hours, Cy3-Manocept-doxorubicin killed 70% of CD206 positive macrophages in tissue cultures. Doxorubicin alone showed no toxicity.

KS organ culture treated with Manocept-doxorubicin resulted in the loss of macrophages and induced programmed tumor cell death and apoptosis in KS HHV8+ spindle cells, and showed anti-HIV activity in HIV infected macrophage cultures.

"We are very encouraged that our Manocept platform, with its unique ability to seek out activated macrophages, may selectively deliver a therapeutic that can kill tumor cells, tumor support cells and virus contained in the macrophage. This activity was seen with a therapeutic that without our delivery system would not be effective on the tumor, the TAM’s or either of the viruses. This data suggests that targeting the activated macrophage is a viable strategy for attacking cancers that have TAM’s. It is well established that depleting TAM’s makes the tumor more susceptible to chemotherapy, radiation therapy and many of the new and emerging immune therapy drugs. In addition the effect of this agent with no known anti-viral properties on killing both HIV and HHV8 suggests a novel anti-viral strategy that will not require development of specific tailored drugs to a given virus," said Michael M. Goldberg, M.D., CEO of Macrophage Therapeutics and Director of Navidea. "We look forward to advancing development of our broad therapeutic platform through animal testing this summer in a number of solid tumor models as well as explore the potential of our technology in CNS diseases, viral diseases and animal models of auto-immune disease. Our goal is to seek strategic collaborations with industry leaders to enable rapid development. Finally, we will host an investor day at the end of the summer where we will review the accumulated data being generated."

Navidea and Macrophage Therapeutics plan a webcast to provide investors with a complete look at the data being presented at the International Workshop on Kaposi’s Sarcoma Herpesvirus (KSHV) and Related Agents conference on July 7, 2015 at 1:00 pm EDT. Webcast details will be available on the Navidea website.

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 Kaposi’s Sarcoma

Kaposi sarcoma (KS) is a cancer that develops from the cells that line lymph nodes or blood vessels. It usually appears as tumors on the skin or on mucosal surfaces such as inside the mouth, but tumors can also develop in other parts of the body, such as in the lymph nodes (bean-sized collections of immune cells throughout the body), the lungs, or digestive tract. The abnormal cells of KS form purple, red, or brown blotches or tumors on the skin. These affected areas are called lesions. The skin lesions of KS most often appear on the extremities, trunk and face. AIDS-related KS is the most common type of KS in the United States which develops in people who are infected with HIV, the virus that causes AIDS. KS can also develop in people whose immune systems have been suppressed after an organ transplant and is called transplant-related KS.1

On July 1, 2015 CEL-SCI Corporation (NYSE MKT: CVM)("CEL SCI" or the "Company") reported that in June it has enrolled 25 patients in its ongoing Phase 3 trial of its investigational immunotherapy Multikine* (Leukocyte Interleukin, Injection) in just diagnosed, not yet treated patients with head and neck cancer (Press release, Cel-Sci, JUL 1, 2015, View Source [SID:1234506541]). Total patient enrollment is now 488 as of June 30, 2015 in the world’s largest Phase 3 study in head and neck cancer.

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A total of 880 patients are expected to be enrolled, through approximately 100 clinical centers in about 25 countries by the end of March 2016.

About the Multikine Phase 3 Study

The Multikine Phase 3 study is enrolling just diagnosed, not yet treated patients with advanced primary squamous cell carcinoma of the head and neck. The objective of the study is to demonstrate a statistically significant improvement in the overall survival of enrolled patients who are treated with the Multikine treatment regimen plus standard of care ("SOC") vs. subjects who are treated with SOC only. Standard of Care for these patients consists of the surgical removal of the tumor and any locally involved lymph nodes, followed by radiotherapy or concurrent radiochemotherapy.

About Multikine

Multikine (Leukocyte Interleukin, Injection) is an investigational immunotherapeutic agent that is being tested in an open-label, randomized, controlled, global pivotal Phase 3 clinical trial as a potential first-line treatment for advanced primary squamous cell carcinoma of the head and neck. Multikine is designed to be a different type of therapy in the fight against cancer: one that appears to have the potential to work with the body’s natural immune system in the fight against tumors.

Multikine is also being tested in a Phase 1 study under a Cooperative Research and Development Agreement ("CRADA") with the U.S. Naval Medical Center, San Diego, as a potential treatment for peri-anal warts in HIV/HPV co-infected men and women. CEL-SCI has also entered into two co-development agreements with Ergomed Clinical Research Limited to further the development of Multikine for cervical dysplasia/neoplasia in women who are co-infected with HIV and HPV and for peri-anal warts in men and women who are co-infected with HIV and HPV.

On July 1, 2015 4SC AG (Frankfurt, Prime Standard: VSC), a discovery and development company of targeted small molecule drugs for cancer and autoimmune diseases, reported that the company has managed to further strengthen its patent portfolio for its lead clinical anti-cancer programme resminostat (Press release, 4SC, JUL 1, 2015, View Source [SID:1234506542]).

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For the epigenetic agent resminostat, an HADC inhibitor targeting in particular HDAC 1, 2, 3 and 6, the US Patent Office has granted the patent for the medical use in cancer indications. The patent relates to the so-called method of treatment claims, and covers medical application of resminostat in mono- and/or combination therapy for cancer indications.

In addition, the Canadian patent authority has granted the composition of matter patent for resminostat. Thus resminostat has now composition of matter protection in all major markets including the US, Europe, Japan, China, South Korea, Russia, India, and now Canada.

The granting of the two patents constitutes an additional protection against potential competitors and thus further strengthens the protection of 4SC’s intellectual property assets, including the composition of matter, mesylate salt and manufacturing patents of resminostat, for which up to date patents have been granted in 58 countries, including the major markets.

Enno Spillner, Chief Executive Officer of 4SC, said: "We are pleased to announce the recent additions to our patent portfolio. The two patents will further strengthen not only the wide strategic position of our resminostat programme but also of 4SC as an important player in the field of epigenetic cancer therapies." Enno Spillner continued: "Especially, the resminostat medical application patent shows the broad possibilities of future use of our lead drug candidate. This is in particular evident in the light of the recently announced additional clinical use by our partner Yakult Honsha in pancreatic and biliary tract cancer as well as our own planned European Phase II trial in the indication of CTCL."

About Resminostat
Resminostat (4SC-201) is an oral histone-deacetylase (HDAC) inhibitor, targeting in particular HDAC 1, 2, 3 and 6, with an innovative epigenetic mechanism of action that potentially enables the compound to be deployed as a novel, targeted tumour therapy for a broad spectrum of oncological indications, both in monotherapy and, in particular, in combination with other cancer drugs. Like other epigenetic therapies, resminostat modifies transcription of genes in cancer cells and, thereby, reprograms the phenotypes of such cancer cells. Additionally, resminostat has immunotherapeutic effects by activating NK cells, restoring MHCI and MHCII proteins and suppression of unspecific immunosuppression. Resminostat is assumed to be able to halt tumour progression and induce tumour regression. Furthermore, due to its epigenetic mode of action resminostat is supposed to 2 develop additional synergetic effects when combined with classical cancer therapies and to counteract the development of tumour cell resistance.

Resminostat – by 4SC and its Japanese partner Yakult – has been investigated or is currently being investigated in a broad clinical campaign comprising liver cancer (HCC), Hodgkin’s Lymphoma (HL), colorectal cancer (CRC), non-small-cell lung cancer (NSCLC), pancreatic and biliary tract cancer. Resminostat is partnered with Yakult Honsha for Japan and with Menarini AP in the Asia Pacific (APAC) region excluding Japan. 4SC is currently in preparations of a randomised, controlled Phase II trial in the indication of advanced cutaneous T-cell lymphoma (CTCL) in Europe.

On July 1, 2015 Exelixis reported yesterday Exelixis’ partner Genentech, a member of the Roche Group, informed Exelixis that, in order to accommodate its review of a supplemental data submission, the U.S. Food and Drug Administration (FDA) has extended the Prescription Drug User Fee Act (PDUFA) action date for its review of Genentech’s New Drug Application (NDA) for cobimetinib by the standard extension period of three months, from August 11, 2015 to November 11, 2015 (Press release, Exelixis, JUL 1, 2015, View Source;p=RssLanding&cat=news&id=2064058 [SID:1234506017]).

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FDA extended its review after Genentech submitted, at FDA request, additional data from coBRIM, the phase 3 registrational trial of cobimetinib and vemurafenib in patients with BRAF V600 mutation-positive advanced melanoma.

Exelixis discovered cobimetinib, a selective inhibitor of MEK, internally and advanced the compound to investigational new drug (IND) status. In late 2006, Exelixis entered into a collaboration agreement with Genentech, under which Exelixis received initial upfront and milestone payments in connection with signing the agreement and submitting the IND. Exelixis was responsible for development of cobimetinib through the determination of the maximum tolerated dose in phase 1, at which point Genentech exercised its option to further develop the compound.

In November 2013, Exelixis exercised its option to co-promote cobimetinib, if approved, in the United States. Exelixis is entitled to an initial equal share of U.S. profits and losses, which will decrease as sales increase, and will share equally in the U.S. marketing and commercialization costs. Exelixis is eligible to receive royalties on any sales of the product outside the United States.

About the Cobimetinib and Vemurafenib Combination

Cobimetinib is a selective inhibitor that blocks the activity of MEK, a protein kinase that is part of a key pathway (the RAS-RAF-MEK-ERK pathway) that promotes cell division and survival. This pathway is frequently activated in human cancers including melanoma, where mutation of one of its components (BRAF) causes abnormal activation in about 50% of tumors. Tumors with BRAF mutations may develop resistance and subsequently progress after treatment with a BRAF inhibitor. In preclinical melanoma models, co-treatment with a BRAF inhibitor and a MEK inhibitor may delay the emergence of resistant tumors. In addition to the combination with vemurafenib in melanoma, cobimetinib is also being investigated in combination with several investigational medicines, including an immunotherapy, in several tumor types, including non-small cell lung cancer, colorectal cancer, triple-negative breast cancer and melanoma.

On January 7, 2015 Soligenix, Inc. (OTCQB: SNGX) (Soligenix or the Company), a late-stage biopharmaceutical company developing products that address unmet medical needs in the areas of inflammation, oncology and biodefense, reported that its SGX301 (synthetic hypericin) development program for the first-line treatment of cutaneous T-cell lymphoma (CTCL) has received "Fast Track" designation from the US Food and Drug Administration (FDA) (Press release, Soligenix, JUL 1, 2015, View Source [SID:1234512918]).

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Fast track is a designation that the FDA reserves for a drug intended to treat a serious or life- threatening condition and one that demonstrates the potential to address an unmet medical need for the condition. Fast track designation is designed to facilitate the development and expedite the review of new drugs. For instance, should events warrant, Soligenix will be eligible to submit a new drug application (NDA) for SGX301 on a rolling basis, permitting the FDA to review sections of the NDA prior to receiving the complete submission. Additionally, NDAs for fast track development programs ordinarily will be eligible for priority review, which imparts an abbreviated review time of approximately six months.

"We are very pleased to have been granted fast track designation from the FDA to go along with the orphan drug designation previously received. We believe that the FDA’s action in granting fast track designation validates the unmet medical need that currently exists for first-line treatment in CTCL and for the potential key role SGX301 can serve as a first-line therapy in this rare, life-threatening disease," stated Christopher J. Schaber, PhD, President and Chief Executive Officer of Soligenix. "With the pivotal Phase 3 protocol now cleared through the FDA and completion of the recent targeted financing, we look forward to working closely with our esteemed Medical Advisory Board to initiate the clinical study in the first half of 2015."

About CTCL
Cutaneous T-cell lymphoma (CTCL) is a class of non-Hodgkin’s lymphoma (NHL), a type of cancer of the white blood cells that are an integral part of the immune system. Unlike most NHLs which generally involve B-cell lymphocytes (involved in producing antibodies), CTCL is caused by an expansion of malignant T-cell lymphocytes (involved in cell-mediated immunity) normally programmed to migrate to the skin. These skin-trafficking malignant T-cells migrate to the skin, causing various lesions to appear that may change shape as the disease progresses, typically beginning as a rash and eventually forming plaques and tumors. Mortality is related to the stage of CTCL, with median survival generally ranging from about 12 years in the early stages to only 2.5 years when the disease has advanced. There is currently no cure for CTCL.

CTCL constitutes a rare group of NHLs, occurring in about 4% of the approximate 500,000 individuals living with the disease. It is estimated, based upon review of historic published studies and reports and an interpolation of data on the incidence of CTCL, that it affects over 20,000 individuals in the US, with approximately 2,800 new cases seen annually.

About SGX301
SGX301 is a novel first-in-class photodynamic therapy utilizing safe visible light for activation. The active ingredient in SGX301 is synthetic hypericin, a potent photosensitizer which is topically applied to skin lesions and then activated by fluorescent light 16 to 24 hours later. Combined with photoactivation, hypericin has demonstrated significant anti-proliferative effects on activated normal human lymphoid cells and inhibited growth of malignant T-cells isolated from CTCL patients. In a published Phase 2 clinical study in CTCL, patients experienced a statistically significant (p ≤ 0.04) improvement with topical hypericin treatment whereas the placebo was ineffective: 58.3% compared to 8.3%, respectively. SGX301 has received orphan drug designation from the FDA.