Caliber and ImmunGene Launch Valor Biotherapeutics, a Joint Venture to Develop Antibody-Interferon Fusion Therapeutics to Treat Cancers

On November 13, 2012 ImmunGene, Inc. (ImmunGene) and Caliber Biotherapeutics, LLC (Caliber) reported the launch of Valor Biotherapeutics, LLC (Valor), a joint venture focused on the clinical development and commercialization of monoclonal antibody-interferon (mAb-IFN) fusion protein therapeutics targeting certain cancers (Press release, Valor Biotherapeutics, NOV 13, 2013, Caliber and ImmunGene Launch Valor Biotherapeutics, a Joint Venture to Develop Antibody-Interferon Fusion Therapeutics to Treat Cancers [SID:1234513256]). The mAb-IFN fusion protein technology was invented in Professor Sherie Morrison’s laboratory at the University of California, Los Angeles and licensed exclusively to ImmunGene. This technology is being used to enable the precise targeting of tumor cells with monoclonal antibodies and their destruction by interferon.

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Valor will combine the assets and resources of Caliber with ImmunGene’s technologies, know-how, and intellectual property (IP). ImmunGene will grant Valor exclusive licenses to its IP for three mAb-IFN fusion product candidates currently in various stages of preclinical development. Caliber will commit sufficient funds to enable Valor to reach certain development milestones for these compounds in the treatment of non-Hodgkin’s lymphoma, multiple myeloma, and breast cancer.

Valor will be led by Rahul Singhvi, Sc.D., Managing Director of Caliber Biotherapeutics, LLC and former President and CEO of Novavax, Inc. Dr. Singhvi will be joined on the Valor board of directors by David Shanahan, a serial entrepreneur, philanthropist and a Caliber founder. Mr. Shanahan is also the founder and President of Gradalis, Inc., a cancer immunotherapy company, and President of the Mary Crowley Cancer Research Center. Dr. Sanjay Khare, CEO of ImmunGene, and Dr. Michael Gresser, Chair of ImmunGene’s scientific advisory board, will also join the Valor board.

Dr. Singhvi commented, "The creation of Valor Biotherapeutics further marks the evolution of Caliber from a technology company into a drug development company with a highly promising pipeline. We intend to leverage our complementary resources to develop these product candidates and welcome the opportunity to work with the highly accomplished ImmunGene team to accomplish our goals."

"We are impressed with the promise of ImmunGene’s mAb-IFN fusion technology in addressing many unmet needs in cancer," said Mr. Shanahan. "We are thrilled to support the development of this technology through our joint venture and demonstrate the potential benefits this technology can bring to cancer patients."

"This joint venture will allow us to accelerate the development of ImmunGene’s antibody interferon fusion drug candidates into human proof-of-concept studies in cancer patients." said Sanjay D. Khare, Ph.D., CEO of ImmunGene. "We believe our technology has the potential to improve the treatment of certain cancers and that Caliber’s unique experience in cancer research will help us realize the clinical and commercial potential of our pipeline through this promising joint venture."

About Monoclonal Antibody – Interferon (mAb-IFN) Fusion Proteins

mAb-IFN fusion proteins are a new class of biotherapeutics that are produced by fusing antibodies to tumor cell-killing cytokines (e.g. IFN). These fusion proteins offer potential advantages because several important properties can be built into a single, genetically engineered molecule. They are thought to kill tumor cells mainly by stimulating apoptosis, in an ADCC (antibody-dependent cell-mediated cytotoxicity)-independent manner. Consequently, these molecules have the potential to be efficacious in patients with defective ADCC mechanisms. In addition, they have the potential to be cytotoxic to tumor cells with low density of targeted surface antigens. The fusion proteins retain the properties of conventional, non-fused antibody therapeutics in stimulating ADCC and complement-dependent cytotoxicity (CDC) functions. Such mAb-IFN fusion proteins have demonstrated superior efficacy and safety in preclinical studies, validating the therapeutic potential of this technology.

Merck Enters into Further Global Co-Development and Commercialization Agreement for PARP Inhibitor with Chinese R&D Company BeiGene

On November 13, 2013 Merck Serono (Merck KGaA) reported that a global licensing, co-development, and commercialization agreement for BeiGene-290 has been signed with BeiGene (Press release BeiGene, NOV 13, 2013, View Source [SID:1234500416]).
The compound, which is a potent poly (ADP-ribose) polymerase (PARP) inhibitor for the treatment of cancer, is currently in preclinical development and is expected to enter clinical development next year. This is the second collaboration agreement between the two companies this year.
PARP inhibitors are thought to target an enzyme family, poly (ADP-ribose) polymerase, which is involved in a number of cellular processes, including DNA repair and programmed cell death.
Under the terms of the collaboration, BeiGene will be responsible for the development and commercialization of BeiGene-290 in China, and Merck will be responsible for the development and commercialization of BeiGene-290 for the rest of the world. BeiGene will receive an undisclosed upfront payment and is eligible to receive further payments of up to € 170 million (US$ 232 million) for the achievement of clinical developmentand potential commercial milestones in both the People’s Republic of China and rest of the world, as well as royalties on net sales.

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Lundbeck Canada launches a new treatment for a rare form of acute leukemia: acute promyelocytic leukemia

On November 13, 2013 it was reported that Health Canada had recently approved Trisenox (arsenic trioxide) for relapsed or refractory acute promyelocytic leukemia (APL) ((Press release Lundbeck, NOV 13, 2013, View Source(ENGLISH)%20-%20November%2013%202013.pdf [SID:1234500348])). This was made possible by a decision from Health Canada’s Therapeutic Products Directorate to remove a prior regulatory prohibition on arsenic containing drug therapies for use in humans and by granting priority review.

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(Filing, 10-Q, Soligenix, NOV 12, 2013, View Source [SID:1234506513])

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Inovio Pharmaceuticals Reports 2013 Third Quarter Financial Results

On November 12, 2013 Inovio Pharmaceuticals reported financial results for the quarter ended September 30, 2013 (Presentation, Inovio, NOV 12, 2013, View Source [SID:1234501084]).

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Total revenue was $9.5 million and $11.7 million for the three and nine months ended September 30, 2013, compared to $855,000 and $3.0 million for the same periods in 2012.

Total operating expenses were $8.7 million and $23.3 million for the three and nine months ended September 30, 2013, compared to $7.1 million and $20.3 million for the same periods in 2012.

The income (loss) from operations prior to other income (expenses) for the three and nine months ended September 30, 2013 was $766,000, or $0.00 per share, and $(11.5 million), or $(0.07) per share, as compared with $(6.3 million), or $(0.05) per share, and $(17.3 million), or $(0.13) per share, for the three and nine months ended September 30, 2012.

The net loss attributable to common stockholders for the three and nine months ended September 30, 2013, was $30.9 million, or $0.16 per share, and $50.6 million, or $0.29 per share, as compared with a net loss attributable to common stockholders of $6.6 million, or $0.05 per share, and $19.0 million, or $0.14 per share, for the three and nine months ended September 30, 2012.

The $24.3 million and $31.6 million increase in net loss attributable to common stockholders for the three and nine months ended September 30, 2013, compared with the same periods in 2012, resulted primarily from a non-cash accounting expense related to the change in fair value of common stock warrants based on a required quarterly mark to market adjustment to reflect changes in the Company’s stock price, which increased significantly in the third quarter.

Revenue

The increase in revenue for the comparable periods was primarily due to $8.4 million of revenue recognized from our agreement with Roche. The increase was also attributable to higher revenue recognized from our PATH Malaria Vaccine Initiative ("MVI") grant, our U.S. Department of Defense Small Business Innovation Research Grant and our grant subcontract with the University of Pennsylvania on universal flu vaccines.

Operating Expenses

Research and development expenses for the three and nine months ended September 30, 2013, were $5.4 million and $15.0 million, compared to $5.0 million and $13.5 million for the same periods in 2012. The increase for the nine month period was primarily due to a $1.1 million sub-license fee payable based on the $10.0 million up-front payment received under our Roche partnership agreement as well as higher costs related to work performed for our Malaria Vaccine Initiative contract.

General and administrative expenses for the three and nine months ended September 30, 2013, were $3.3 million and $9.3 million versus $2.7 million and $7.9 million for the same periods in 2012. The increase for the nine month period was primarily due to an increase in rent expense related to deferred rent on the new building lease as well as transaction costs associated with the issuance of warrants in the 2013 financing, among other variances.

Capital Resources

As of September 30, 2013, cash and cash equivalents plus short-term investments were $46.3 million compared with $13.8 million as of December 31, 2012.

On March 7, 2013, we closed an underwritten offering of 27,377,266 shares of our common stock and warrants to purchase an aggregate of up to 13,688,633 shares of common stock. The shares and warrants were sold in units at a price of $0.55 per unit, with each unit consisting of one share of common stock and a warrant to purchase 0.5 shares of common stock at an exercise price of $0.7936 per share.

During the nine months ending September 30, 2013, the Company sold 14,011,526 shares of common stock under its ATM common stock sales agreement for net proceeds of $15.1 million, with an average price of $1.11 per share. Stock options and warrants to purchase 22,094,569 shares of common stock were exercised for total proceeds to the Company of $19.1 million.

Subsequent to the quarter, the Company received an additional $11.1 million in new capital. The Company sold 348,995 shares of common stock under its ATM common stock sales agreement for net proceeds of $782,000, with an average price of $2.31 per share. Warrants to purchase 375,000 shares of common stock were exercised for total proceeds of $298,000. Roche paid the Company $10 million as the upfront payment for a partnership agreement announced during the third quarter (details below).

As of November 8, 2013, the company had 208.4 million shares outstanding and 239.6 million shares on a fully diluted basis.

Based on management’s projections and analysis, the Company believes that cash and cash equivalents are sufficient to meet its planned working capital requirements into the first quarter of 2016.

Inovio’s balance sheet and statement of operations is provided below. Form 10-Q providing the complete 2013 third quarter financial report can be found at: View Source

Corporate Update

Corporate Development

In a major commercial development for the Company, Inovio announced that Roche and Inovio entered into an exclusive worldwide license agreement to research, develop and commercialize Inovio’s highly-optimized, multi-antigen DNA vaccine products targeting prostate cancer and hepatitis B. Roche licensed Inovio’s therapeutic vaccines INO-5150 for prostate cancer and INO-1800 for hepatitis B as well as the use of Inovio’s CELLECTRA electroporation technology for delivery of these vaccines. Roche also obtained an option to license additional vaccines in connection with a collaborative research program for prostate cancer.

Roche agreed to an upfront payment to Inovio of $10 million (paid subsequent to the quarter), will pay all preclinical and clinical development costs for these products, and will make milestone payments potentially up to $412.5 million upon reaching certain development and commercial milestones for INO-5150 and INO-1800. Additional development milestone payments could be made to us if Roche pursues other indications with INO-5150 or INO-1800. Inovio is entitled to receive up to double-digit tiered royalties on product sales.

Inovio has continuing discussions with other large pharmaceutical companies interested in potential strategic partnerships to advance the development of Inovio’s numerous SynCon immunotherapy and vaccine products.

Clinical Development

Inovio previously reported that its SynCon immunotherapy against HPV-caused pre-cancers and cancers (VGX-3100), delivered with its CELLECTRA electroporation technology, achieved best-in-class T-cell immune responses that generated a strong killing effect against cells targeted by this therapeutic vaccine. In this quarter, Inovio completed enrollment of its double-blinded, placebo-controlled, randomized phase II clinical trial (HPV-003) focused on cervical dysplasia and expects to report unblinded efficacy data in mid-2014. Inovio has initiated preparatory activities for a potential phase III study and also plans to initiate phase II studies of VGX-3100 against HPV-caused cervical cancer and head and neck cancer in 2014.

In partnership with Roche, we intend to launch our prostate cancer immunotherapy (INO-5150) into phase I in the first half of 2014. Preclinical results indicated that this therapeutic vaccine induced potent antibody and T-cell responses in animal models, initial evidence that our concept for a DNA vaccine comprising a broader set of antigens delivered with electroporation may improve the breadth and effectiveness of a prostate cancer immunotherapy. The start of this phase I study will trigger the first milestone payment from Roche.

Inovio and Roche are conducting the preclinical work required to advance INO-1800, Inovio’s hepatitis B therapeutic vaccine, into a phase I clinical trial. Prior preclinical data showed that INO-1800 generated robust T-cell and antibody responses that led to the elimination of targeted liver cells in mice, indicating the potential to treat human hepatitis B infection and prevent progression of the infection to liver cancer.

Phase I data from Inovio’s PENNVAX-B preventive HIV DNA vaccine trial was published in the Journal of Infectious Diseases. Results from this trial showed best-in-class T-cell responses, with delivery with Inovio’s optimized electroporation technology achieving a seven-fold increase (7% to 52%) in the response rate of subjects with robust CD8+ killer T-cells compared to delivery without electroporation. Knowledge gained from the study of this single-clade HIV vaccine has been incorporated into the Company’s globally-oriented, multi-clade PENNVAX-GP, which is now Inovio’s primary preventive and therapeutic HIV DNA vaccine candidate. Based on manufacturing delays, Inovio expects the phase I study for this vaccine to begin in the first half of 2014.

Subsequent to the quarter, Inovio and its partner VGX International announced that VGX has initiated a phase I clinical trial of Inovio’s highly optimized therapeutic hepatitis C (HCV) DNA vaccine (INO-8000/VGX-6150) delivered with its CELLECTRA device. Published preclinical results from this multi-antigen SynCon HCV vaccine demonstrated robust T-cell responses in the liver as well as in the periphery. This study is being fully funded by VGX and will be conducted at multiple study sites in Korea to test safety, tolerability, and immunogenicity. Additional clinical studies will begin in the U.S. in 2014.

Inovio continues to focus on its most important commercial opportunities and proprietary programs funded by third parties. To build on promising preclinical and clinical data from Inovio’s universal influenza vaccine program, the Company is actively seeking additional grant funding and partnerships to further develop its potentially paradigm-changing flu products.

The University of Southampton has indicated that its UK phase II clinical study of its WT1 leukemia vaccine delivered using Inovio’s electroporation technology is not currently recruiting new subjects due to an interruption in sponsor funding. Efforts are under way to re-establish funding, however, the study is on hold pending the outcome of these refunding efforts. There have been no safety concerns identified during the study. Inovio’s aim is to maximize shareholder value by advancing its wholly-owned, integrated proprietary SynCon vaccine and electroporation technology platform. Inovio has designed a SynCon cancer vaccine candidate based on the WT1 antigen and has generated promising preclinical data. This new candidate will be a part of multiple cancer immunotherapeutic programs in Inovio’s growing oncology pipeline.

Preclinical Development

In addition to VGX-3100 and INO-5150, Inovio continues to expand its cancer immunotherapy product pipeline. The first of several to move from research into product development is INO-1400, Inovio’s hTERT DNA-based cancer immunotherapy. INO-1400 generated robust and broad immune responses that were 18-fold higher than the previous best results of a peer’s hTERT therapeutic vaccine, broke the immune system’s tolerance to its self-antigens, induced T-cells with a tumor-killing function, and increased the rate of survival when delivered with Inovio’s CELLECTRA electroporation technology. Because high levels of hTERT expression are found in 85% of human cancers, this antigen has potential as the basis of a "universal" cancer therapeutic. Inovio plans to advance INO-1400 into clinical trials to treat breast and lung cancers in 2014.

Published in Infection & Immunity, Inovio announced that its SynCon malaria vaccine generated robust and long-lasting T-cell responses that exhibited the functional ability to kill and eliminate malaria-infected cells in small animals and non-human primates. Researchers also found vaccine induced CD-8+ "killer T-cells" in the liver, which is essential for rapid elimination of liver-stage malaria parasites. Inovio expects that a phase I/IIa clinical trial will be initiated in 2014.

Responding to the 2013 H7N9 influenza outbreak, Inovio completed the design, optimization, and manufacturing of an H7N9 DNA vaccine within two weeks. Preclinical data showed that 100% of vaccinated mice were protected against sickness and death when they were challenged with a lethal dose of H7N9 virus. This study further highlights the ability of Inovio’s SynCon vaccine to create cellular immune responses that could reduce the severity of H7N9 infection in a person that acquires the virus and limit the spread of the virus in a pandemic setting.

Several significant new applications of DNA plasmid technology delivered using electroporation have been unveiled in peer-reviewed papers this quarter. First, Inovio announced its success in generating therapeutic monoclonal antibodies using DNA plasmid technology delivered using electroporation. Published in Human Vaccines and Immunotherapeutics, this study demonstrated that a highly optimized DNA-based monoclonal antibody in mice generated antibody molecules in the bloodstream possessing desirable functional activity including high antigen-binding and HIV-neutralization capabilities against diverse strains of HIV viruses. In addition, this DNA delivery strategy resulted in a rapid increase in antibody levels in mice. These results were not previously achievable with other DNA based or viral technologies. DNA-based monoclonal antibodies have the potential to become a powerful technology against cancers, autoimmune diseases, and neurological diseases and compete favorably in the $50 billion monoclonal antibody product market.

Inovio highlighted another new application of DNA technology in a paper highlighting the ability to stimulate blood vessel growth, limb function recovery, and survival from limb necrosis and amputation, which may be beneficial for the treatment of critical limb ischemia (CLI) and other forms of peripheral arterial disease (PAD). This result was achieved with a DNA therapy encoded for hypoxia-inducible factor-1 alpha (HIF-1a). Results from this mice study were published in the Journal of Vascular Surgery. PAD patients currently have very limited treatment options and this disease represents a multi-billion dollar market opportunity.

These new developments represent significant new medical applications of our potent product development platform that could bring about additional support funding as well as corporate partnerships.