On July 7, 2015 Innate Pharma reported that the co-development and commercialization agreement with AstraZeneca on Innate Pharma’s proprietary anti-NKG2A antibody, IPH2201 (see announcement press release as of April, 24, 2015), received HSR clearance (Press release, Innate Pharma, JUL 6, 2015, View Source [SID:1234506176]). The companies will now begin to work together to accelerate and broaden the development of IPH2201, including in combination with MEDI4736, an anti-PD-L1 immune checkpoint inhibitor developed by MedImmune.

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On June 30, 2015, Innate Pharma received the initial payment of $250 million from AstraZeneca.

On July 2, 2015 Provectus Biopharmaceuticals reported that data from its phase 1 study of PV-10 for chemoablation of hepatocellular carcinoma (HCC) and cancer metastatic to the liver was presented at the ESMO (Free ESMO Whitepaper) 17th World Congress on Gastrointestinal Cancer (ESMO-GI) (Press release, Provectus Pharmaceuticals, JUL 2, 2015, http://www.pvct.com/pressrelease.html?article=20150702.1 [SID:1234506021]). The main conclusion was that preliminary evidence of efficacy in treatment of liver cancers with PV-10 was observed. The poster presentation was made by Eric Wachter, Ph.D., Chief Technology Officer of Provectus.

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Provectus has previously reported data on clinical and nonclinical testing of intralesional PV-10, a 10% solution of rose bengal, as an investigational treatment for metastatic melanoma, where it has demonstrated high rates of complete response and durable local control in melanoma lesions. The current phase 1 study reported at ESMO (Free ESMO Whitepaper)-GI was designed to assess safety, pharmacokinetics, and preliminary efficacy of PV-10 in subjects with non-resectable HCC or other types of cancer metastatic to the liver.

In the phase 1 liver study, subjects having a target lesion in the liver at least 1 cm in diameter were administered a single percutaneous injection of PV-10 into their target lesion. Plasma concentrations of PV-10 from 1 hour to 28 days after injection were measured. Radiologic assessments of the injected target lesion were performed to determine response over an initial 28-day and longer term 9-15 month follow-up period. Serum levels of potential liver injury markers were measured, and adverse events recorded.

In the initial study cohort, six subjects received PV-10 injections in two successive escalating dose cohorts of 0.25 and 0.50 mL per cm3 lesion volume. Significant adverse events were limited to injection site and photosensitivity reactions that resolved without sequelae. All injected tumors were stable in size at 28 days, and among four of the initial six tumors that had longer-term assessment, two had partial response.

Based on these data, the researchers concluded that preliminary efficacy in treatment of liver tumors with PV-10 was observed with acceptable tolerability. The study is continuing at three study centers with two expansion cohorts to further assess safety and response in HCC and other cancers metastatic to the liver.

The poster is now available online at: http://www.pvct.com/publications/ESMO-2015-PV-10-LC-01.pdf.

About ESMO (Free ESMO Whitepaper) 17th World Congress on Gastrointestinal Cancer

The ESMO (Free ESMO Whitepaper) 17th World Congress on Gastrointestinal Cancer is the premier global event in the field, encompassing malignancies affecting every component of the gastrointestinal tract and aspects related to the care of patients with gastrointestinal cancer, including screening, diagnosis and the latest management options for common and uncommon tumors. For additional information about the ESMO (Free ESMO Whitepaper) 17th World Congress, please visit View Source

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 2, 2015 Navidea Biopharmaceuticals and its subsidiary, Macrophage Therapeutics reported that imaging results from the Manocept clinical trial in Kaposi’s Sarcoma (KS) and other preclinical studies were presented at the 18th International Workshop on Kaposi’s Sarcoma Herpesvirus (KSHV) and Related Agents in Hollywood, Florida (Press release, Navidea Biopharmaceuticals, JUL 2, 2015, View Source;p=RssLanding&cat=news&id=2064415 [SID:1234506023]). The clinical imaging study, using Tc 99m tilmanocept, a Manocept platform product, in both HIV+ and HIV- patients suggests that KS tumor lesions, both cutaneous and suspected extra-cutaneous sites, can be easily visualized and mapped, demonstrating that this technique may potentially provide a means for routine patient assessment. The results also show that use of Manocept represents a potential therapeutic pathway for targeting tumor associated macrophages (TAMs). Manocept agents are designed to target CD206, which is highly expressed on TAMs and the KS tumor itself. As a potential therapeutic, Manocept could be used as a precision vehicle to deliver payloads to tumor sites throughout the body.

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"These pre-clinical and clinical studies support using Kaposi’s sarcoma as a model tumor system for evaluating therapeutic approaches for the Manocept platform in other forms of solid tumors," commented Michael Tomblyn, M.D., Navidea’s Chief Medical Officer. "They provide evidence that Manocept agents can target CD206 and are internalized into tumor associated macrophages and tumor cells. This along with clinical observations that demonstrate tilmanocept can be used to image KS tumors both externally and internally indicates excellent potential for immunotherapeutic utility."

"Using a targeted imaging agent like tilmanocept in this group of HHV8+patients represents an elegant approach to potentially detect internal KS lesions that would previously be difficult or impossible to non-invasively locate," commented Toby Maurer, M.D., FAAD, Professor of Dermatology at the University of California, San Francisco (UCSF), and Chief of Dermatology at San Francisco General Hospital and Trauma Center, who co-led the clinical study at UCSF with Michael S. McGrath, M.D., PhD. "Further, the specificity and the ability to quantify tumor burden could enable regular patient evaluations and monitoring of therapeutic effectiveness addressing important unmet patient needs."

Five Human Herpes Virus8 positive (HHV8+) patients (4 HIV+, 1HIV-) were enrolled in the NAV03-12 study. Patients received a single subcutaneous injection of Technetium Tc 99m tilmanocept in the region of a cutaneous KS lesion and imaging was performed at 1, 4 and 24-hours post-injection to visualize localization of tilmanocept. Results represented by whole body Single-Photon Emission Computed Tomography (SPECT/CT) imaging scans from study patients were presented. Collectively, the scans show localization of tilmanocept and detected multiple cutaneous lesions in the extremities, face and genitalia, as well as extra-cutaneous localization found in the nasopharynx, lymph nodes and brain. Results also indicate that KS lesions are anatomically linked in chains by and within the lymph ducts. The study concludes that both HIV+ and HIV- patients have pan-tumor expression of CD206, strongly suggests tilmanocept crosses the blood brain barrier and that a Manocept-drug conjugate may have the potential as a therapeutic with high target effect and low off-target concerns.

The data from these studies also suggest a novel theory on the genesis of KS in which KS arises from an HHV8 infected macrophage type cell and its interaction with the lymphatic system. This interaction provides the means for access of the KS through CD206 receptor for diagnosis, evaluation, and potential therapy using the Manocept platform.

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 the Manocept CD206-targeting platform

The Manocept platform is predicated on the ability to specifically target the CD206 mannose receptor expressed on macrophages. Macrophages play important roles in many disease states and are an emerging target in many disorders. This flexible and versatile platform acts as an engine for purpose-built molecules that may enhance diagnostic accuracy, clinical decision-making, targeted treatments and ultimately patient care. As a diagnostic tool, the Manocept technology has the potential to utilize a breadth of imaging modalities, including SPECT, PET, intra-operative and/or optical-fluorescence detection. By adding a therapeutic agent on the Manocept molecular backbone, there is the potential to develop novel, targeted immunotherapies specifically designed to selectively deliver an agent that can kill or alter disease-associated macrophages. Navidea’s FDA-approved precision diagnostic imaging agent, Lymphoseek (technetium 99m tilmanocept) injection, is representative of the platform’s ability to successfully exploit this mechanism and offer the potential for development of new CD206-targeted diagnostic agents and therapeutics.

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.