10-K – Annual report [Section 13 and 15(d), not S-K Item 405]

RXi Pharmaceuticals has filed a 10-K – Annual report [Section 13 and 15(d), not S-K Item 405] with the U.S. Securities and Exchange Commission (Filing, 10-K, RXi Pharmaceuticals, MAR 30, 2015, View Source [SID1234502869]).

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Aduro Biotech Establishes Major Collaboration with Novartis for Global Research, Development and Commercialization of Immuno-Oncology Products Derived from its Proprietary STING-Targeted CDN Platform Technology

On March 30, 2015 Aduro Biotech reported the establishment of a major collaboration with Novartis for the worldwide research, development and commercialization of novel immuno-oncology products derived from Aduro’s cyclic dinucleotide (CDN) approach to target the STING (Stimulator of Interferon Genes) receptor, that, when activated, is known to initiate broad innate and adaptive tumor-specific immune responses (Press release, Aduro BioTech, MAR 30, 2015, View Source [SID:1234502923]).

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"This is a tremendous validation of our CDN technology and the preclinical data that we’ve generated in the program thus far. We look forward to collaborating with Novartis to begin a Phase 1 clinical trial with our first novel immuno-oncology candidate."

"We are extremely pleased to enter into this relationship with Novartis as their strong commitment and spirit of collaboration was evident early in our conversations," said Stephen T. Isaacs, chairman, president and chief executive officer of Aduro. "We believe they are an ideal partner not only because of their stature as a premier healthcare company with a major focus in oncology, but also because they demonstrated a keen understanding and appreciation for our novel CDN approach, have synergistic innovation and scientific strengths and of course offer tremendous clinical and commercial expertise which we expect will broaden and accelerate the potential to bring products developed from this novel technology to patients in need."

Under the terms of the agreement, Novartis will make an upfront payment of $200 million to Aduro and, if all development milestones are met, Aduro is eligible to receive up to an additional aggregate amount of $500 million. In addition, Novartis has made an initial 2.7 percent equity investment in Aduro for $25 million, with a commitment for another $25 million investment at a future date.

Aduro will lead commercialization activities and will book sales in the United States for any products developed and commercialized pursuant to this collaboration, with Novartis leading commercialization activities in all other regions. The companies will share in profits, if any, in the United States, Japan and major European countries. Novartis will pay Aduro a mid-teens royalty for sales in the rest of the world.

Novartis’ Mark C. Fishman, M.D., president of the Novartis Institutes for BioMedical Research, commented, "We are delighted to collaborate with Aduro. We believe this target is among the most exciting in oncology today, the drug candidate to be of the highest quality, and the talent of our new colleagues from Aduro to be fantastic. We anticipate many clinical opportunities will be explored with the CDN approach, both directly and in combination with other agents."

The agreement covers the joint research, development and commercialization of CDN-based therapies in the field of oncology. Aduro maintains rights to its CDN technology in all other therapeutic areas, including infectious disease and autoimmunity, among others.

Thomas W. Dubensky, Jr., Ph.D., chief scientific officer for Aduro added, "This is a tremendous validation of our CDN technology and the preclinical data that we’ve generated in the program thus far. We look forward to collaborating with Novartis to begin a Phase 1 clinical trial with our first novel immuno-oncology candidate."

Last year, Dr. Dubensky presented preclinical data at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Tumor Immunology and Immunotherapy Conference demonstrating potent anti-tumor activity in preclinical models treated with ADU-S100, the company’s compound based on its CDN technology. The preclinical studies included evaluation of ADU-S100 to stimulate and activate the STING pathway as an approach to generate an immune response that can specifically attack tumor cells. ADU-S100 is a novel synthetic CDN-based molecule that was developed based on its ability to stimulate human immune cells from a large pool of human donors that comprised all of the known STING receptors. In preclinical mouse tumor models, the data showed that direct intratumoral injection of ADU-S100 into melanoma, colon and breast tumors profoundly inhibited tumor growth both locally and systemically, with a durable response that provided protection against tumor regrowth and significantly inhibited growth of distal tumors. In addition, Aduro believes the immune-mediated destruction of distal tumors could be significantly enhanced by a combination of ADU-S100 and radiotherapy, a combination that may eventually be tested in human clinical trials.
About Cyclic Dinucleotide (CDN)

Aduro’s proprietary CDN product candidates are synthetic small molecule immune modulators that are designed to target and activate a receptor known as the Stimulator of Interferon Genes, or STING, receptor. The STING receptor is generally expressed at high levels in immune cells, including dendritic cells. Once activated, the STING receptor initiates a profound innate immune response through multiple pathways, inducing the expression of a broad profile of cytokines, including interferons and chemokines. This subsequently leads to the development of an effective tumor antigen-specific T cell adaptive immune response.

ZIOPHARM-Intrexon Synthetic Immuno-Oncology Programs Strengthened Through Collaboration With Merck Serono

On March 30, 2015 ZIOPHARM Oncology and Intrexon reported their oncology programs will be strengthened through Intrexon’s new global collaboration focused exclusively on novel chimeric antigen receptor T-cell (CAR-T) products with Merck Serono, the biopharmaceutical division of Merck KGaA, Darmstadt, Germany (Press release, Intrexon, MAR 30, 2015, View Source;p=RssLanding&cat=news&id=2030444 [SID:1234502865]). Intrexon will share the economic provisions of this collaboration, including upfront payment, milestones and royalties, equally with ZIOPHARM.

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Under the collaboration Merck Serono will elect CAR-T targets, two initially, for which it will provide certain research funding. Through its agreement with Intrexon, ZIOPHARM will be responsible for any additional research and development expenditures. Once these candidates reach investigational new drug (IND) stage, the programs will be transferred to Merck Serono for clinical development and commercialization. ZIOPHARM and Intrexon will also independently conduct research and development on other CAR-T candidates, with Merck having the opportunity during clinical development to opt-in. ZIOPHARM’s other oncology programs will continue through its Exclusive Channel Collaboration (ECC) with Intrexon.

"Controlled CAR-T treatments hold the promise of delivering the powerful benefit of a targeted immune response to cancer with the ability to modulate immune toxicity, leading to safer, more efficacious treatments," said Jonathan Lewis, M.D., Ph.D., Chief Executive Officer of ZIOPHARM. "The collaboration with Merck Serono brings world-class resources to our development efforts that greatly enhance our ability to translate CAR-T therapies from bench to bedside."

"Harnessing the power of the immune system in a regulated manner is key to address the challenges of current CAR-T approaches and combat malignancies with adoptive cell therapies," said Gregory Frost Ph.D., Senior Vice President and Head of Intrexon’s Health Sector. "We believe our alliances with Merck Serono and ZIOPHARM will accelerate progress in our synthetic immuno-oncology pipeline and drive next-generation medicines to market."

R.J. Kirk, Chairman and CEO of Intrexon, commented, "The success of our partners is our #1 goal so it is gratifying for us to see the progress being made in the programs initiated under our ECC with ZIOPHARM. We look forward to seeing this progress accelerating in the coming months and years."

CRT and BioInvent expand collaboration with University of Southampton scientists to develop new immunotherapy treatments for cancer

On March 30, 2015 Cancer Research Technology (CRT), the commercialisation and development arm of Cancer Research UK and BioInvent International (OMXS: BINV) reported the start of a two-year research collaboration with leading antibody researchers at the University of Southampton (Press release, Cancer Research Technology, MAR 30, 2015, View Source [SID1234523210]).

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The program aims to develop new immunotherapy treatments for cancer based on preclinical work by the Southampton group showing the potential to treat cancer using antibodies targeting OX40 and 4-1BB – known ‘co-receptors’ that help stimulate the production of killer T-cells during an immune response.

One of the ways that tumour cells avoid detection is by suppressing immune responses to stop functional tumour specific T-cells from being produced. The team aims to develop antibodies that can reverse this process to stimulate the immune system to fight the cancer.

Terms of the collaboration were not disclosed, however, BioInvent has the option to take out a license to commercialise any promising results, with the parties receiving milestone payments and a share of potential revenues.

The first phase of the project aims to identify and then validate the effectiveness of the best class of antibodies to target OX40 and 4-1BB. This work will be carried out in Lund, Sweden, and Southampton, UK, using highly specialised assays and expertise developed through a prior long-standing collaboration between BioInvent and the University of Southampton.

Professor Martin Glennie, who is leading the team in Southampton, said: "Immunotherapy is an extremely exciting field to be working in at the moment. Some of the most promising findings so far have involved drugs that block the signals cancers produce to dampen down the immune system. We’re taking a slightly different approach by engineering antibodies that effectively boost the immune system to recognise and fight the cancer. This research collaboration will develop and refine that approach, paving the way for the first patient trials to begin within the next few years."

Björn Frendéus, PhD, Chief Scientific Officer of BioInvent and honorary Professor at the University of Southampton, said: "The field of Immuno-oncology is rapidly expanding and offers new hope in the treatment of cancers. We will increase the likelihood of identifying successful clinical candidates against OX40 and 4-1BB by accessing unique and complementary preclinical models, and by screening existing preclinical leads as well as generating new leads with our antibody discovery platform F.I.R.S.T. together with the team at Southampton."

Dr Keith Blundy, chief executive of Cancer Research Technology, said: "We’re pleased to be extending our ongoing relationship with BioInvent, whose cutting-edge antibody technologies will be an asset to this project. This is a prime example of how pooling resources and expertise from both industry and academia makes it possible to bring potential new treatments to patients that may otherwise have taken years to reach the clinic."

CRT and Bioinvent expand collaboration with University of Southampton scientists to develop new immunotherapy treatments for cancer

On March 30, 2015 Cancer Research Technology and BioInvent International reported the start of a two-year research collaboration with leading antibody researchers at the University of Southampton (Press release, Cancer Research UK, MAR 30, 2015, View Source [SID:1234502872]).

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The program aims to develop new immunotherapy treatments for cancer based on preclinical work by the Southampton group showing the potential to treat cancer using antibodies targeting OX40 and 4-1BB – known ‘co-receptors’ that help stimulate the production of killer T-cells during an immune response.

One of the ways that tumour cells avoid detection is by suppressing immune responses to stop functional tumour specific T-cells from being produced. The team aims to develop antibodies that can reverse this process to stimulate the immune system to fight the cancer.

Terms of the collaboration were not disclosed, however, BioInvent has the option to take out a license to commercialise any promising results, with the parties receiving milestone payments and a share of potential revenues.

The first phase of the project aims to identify and then validate the effectiveness of the best class of antibodies to target OX40 and 4-1BB. This work will be carried out in Lund, Sweden, and Southampton, UK, using highly specialised assays and expertise developed through a prior long-standing collaboration between BioInvent and the University of Southampton.

Professor Martin Glennie, who is leading the team in Southampton, said: "Immunotherapy is an extremely exciting field to be working in at the moment. Some of the most promising findings so far have involved drugs that block the signals cancers produce to dampen down the immune system. We’re taking a slightly different approach by engineering antibodies that effectively boost the immune system to recognise and fight the cancer. This research collaboration will develop and refine that approach, paving the way for the first patient trials to begin within the next few years."

Björn Frendéus, PhD, Chief Scientific Officer of BioInvent and honorary Professor at the University of Southampton, said: "The field of Immuno-oncology is rapidly expanding and offers new hope in the treatment of cancers. We will increase the likelihood of identifying successful clinical candidates against OX40 and 4-1BB by accessing unique and complementary preclinical models, and by screening existing preclinical leads as well as generating new leads with our antibody discovery platform F.I.R.S.T. together with the team at Southampton."

Dr Keith Blundy, chief executive of Cancer Research Technology, said: "We’re pleased to be extending our ongoing relationship with BioInvent, whose cutting-edge antibody technologies will be an asset to this project. This is a prime example of how pooling resources and expertise from both industry and academia makes it possible to bring potential new treatments to patients that may otherwise have taken years to reach the clinic."

ENDS

For Cancer Research UK\CRT press media enquiries please contact the press office on +44 203 469 8300 or, out-of-hours, the duty press officer on +44 7050 264 059.
Notes to Editor

About OX40 and 41BB

4-1BB and OX40 are members of the TNF receptor superfamily.

4-1BB is expressed on a range of different immune cells including T cells. 4-1BB signalling is a stimulatory signal that enhances T cells. In pre-clinical studies agonistic anti- 4-1BB antibodies stimulate the expansion of antigen-specific CD8 T cells, reverses CD8 T cell anergy, prevents suppression by regulatory T cells, boosts memory CD8 T cell expansion and anti-tumour immunity.

OX40 is expressed on activated CD4 and CD8 T cells, regulatory CD4 T cells, memory CD4 T cells and NKT cells. OX40 signalling is critical for the survival of antigen-primed CD4 T cells and CD4 T cell memory. It plays a role in enhancing survival and effector cell differentiation of CD8 T cells during priming, and is important for T cell expansion during secondary responses. In mouse models of cancer, anti-OX40 antibodies promote anti-tumour immunity through activation of CD8 T cells and the inhibition of regulatory CD4 T cell function within the tumour.