On July 12, 2016 Juno Therapeutics, Inc. (Nasdaq: JUNO), a biopharmaceutical company focused on re-engaging the body’s immune system to revolutionize the treatment of cancer, reported that the U.S. Food and Drug Administration has removed the clinical hold on the Phase II clinical trial of JCAR015 (known as the "ROCKET" trial) in adult patients with relapsed or refractory B cell acute lymphoblastic leukemia (r/r ALL) (Press release, Juno, JUL 12, 2016, View Source [SID:1234513848]).

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Under the revised protocol, the ROCKET trial will continue enrollment using JCAR015 with cyclophosphamide pre-conditioning only.

On July 12, 2016 X-Chem, Inc., a privately held biotechnology company focused on applying its innovative drug discovery capabilities to the generation of novel small molecule therapeutics, and Bayer reported that they have entered into an expanded global drug discovery collaboration across multiple therapeutic areas and target classes (Press release, x-chemrx, JUL 12, 2016, View Source [SID:1234513846]). The new agreement extends Bayer’s access to X-Chem’s DEX technology which is based on DNA-encoded libraries of small molecules with more than 120 billion molecules. The aim of the collaboration is to discover innovative lead structures for complex drug targets in areas of high unmet medical need.

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The two partners have been working together successfully under a research collaboration since 2012 and Bayer has already licensed two programs for multiple series of small molecules from X-Chem that address complex target structures such as protein:protein interactions. The new multi-year collaboration agreement will significantly expand the scope and duration of the partnership.

"Bayer and X-Chem have built a strong relationship delivering outcomes that have exceeded expectations. Complementing our in-house expertise with technologies and know-how of excellent partners is an integral part of our innovation strategy at Bayer," said Professor Andreas Busch, member of the Executive Committee of Bayer AG’s Pharmaceuticals Division and Head of Drug Discovery. "We have identified the DEX platform as a highly valuable extension for our drug discovery efforts. We are looking forward to working with X-Chem on some of our highest-priority targets, for which X-Chem’s platform is ideally suited."

Under the terms of this new agreement, X-Chem will receive an up-front payment, research and development funding, as well as potential pre-clinical, clinical and regulatory milestone payments, up to a total of $528 million. Bayer has an exclusive option to license any programs generated in the course of the collaboration. X-Chem will also receive royalties and sales milestones for each successfully commercialized drug that results from a licensed collaboration program.

"X-Chem is making significant inroads toward the discovery of small molecule drug candidates using its ultra-large screening library. With multiple successes across our partnerships, the DEX platform has been broadly validated to deliver novel chemical entities against a wide array of targets, including difficult targets," said Rick Wagner, Ph.D., Chief Executive Officer of X-Chem. "We are fortunate to have Bayer as a major strategic partner, and we are looking forward to expanding this strong and successful relationship. X-Chem is excited to continue working with Bayer on a wider array of diseases and conditions with significant unmet medical needs."

About the DNA-Encoded X-Chem (DEX) Library and Platform
Due to the size and diversity of the DEXTM library, X-Chem can discover multiple series of novel, potent and selective lead compounds at an unprecedented rate of success against a wide range of targets, including some that previously failed using conventional screening methods. A number of proprietary innovations in library design, screening methodology and bioinformatics underlie the exceptional performance of the DEXTM platform. In particular, X-Chem’s approach to library construction allows for additional chemical reactions to become useable in DNA-encoded library synthesis. Together, these developments result in a much greater repertoire of diversity for small molecules, which cover a range of categories including fragment molecules, small molecular weight heterocyclic compounds, and macrocyclic structures. This diverse library, combined with a heightened ability to detect active molecules, has yielded a robust process that has been highly successful against targets categorized as difficult or intractable.

About DNA-Encoding
The X-Chem drug discovery engine is based on a library, currently in excess of 120 billion compounds and growing, generated by iterative combinatorial synthesis of small molecules tethered to DNA tags that record the synthetic history of the small molecule. Every small molecule in the library has a unique DNA barcode attached it. The library is screened as a mixture using affinity-based binding to a target of interest. Certain rare molecules in the library that bind to the target can be "fished out," while the rest of the molecules are washed away. DNA sequencing methods are then used to detect molecules that are enriched when bound to the target. The diverse nature of the library produces multiple families or clusters of related molecules that bind to the target, forming a basis for emergent structure-activity relationships. Structure-activity relationships are typically used by medicinal chemists to guide iterative chemical maturation of a molecule into a drug. Based on the synthetic history encoded in the DNA sequence information, molecules are then made without the DNA tag attached, and tested for activity in conventional assays.

On July 12, 2016 ZIOPHARM Oncology, Inc. (Nasdaq:ZIOP), a biopharmaceutical company focused on new cancer immunotherapies, reported plans for a Phase I adoptive cellular therapy clinical trial utilizing autologous T cells transduced with lentivirus to express a CD33-specific chimeric antigen receptor (CAR) in patients with relapsed or refractory acute myeloid leukemia (AML) (Press release, Ziopharm, JUL 12, 2016, View Source [SID:1234513844]). The upcoming trial will be the second initiated at The University of Texas MD Anderson Cancer Center under the research and development agreement among ZIOPHARM, Intrexon Corporation (NYSE:XON), and MD Anderson to expeditiously move promising treatments from the bench to the clinic.

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"By targeting myeloid cells with a CD33-specific CAR, we have the opportunity to leverage T-cell mediated cytotoxicity in a highly directed manner," said Francois Lebel, M.D., Executive Vice President, Research and Development, Chief Medical Officer at ZIOPHARM. Dr. Lebel continued, "Following a recent review by the Recombinant DNA Advisory Committee, we anticipate progressing plans for this Phase I trial in the second half of 2016 to move this promising treatment closer to the clinic for patients with relapsed or refractory AML who have poor prognosis."

The American Cancer Society estimates that there will be approximately 20,000 new cases of AML and over 10,000 patient deaths from AML in the United States in 2016. AML is a rapidly progressing cancer of the blood and bone marrow characterized by uncontrolled proliferation of immature blast cells with multiple associated gene mutations. A majority of AML patients relapse or present with refractory disease and have overall poor prognosis.

Preclinical studies demonstrated that lentiviral transduced CAR-T cells targeting CD33 exhibit specific cytotoxic activity for CD33+ AML cells. A proof-of-concept study utilizing an in vivo mouse model for AML showed that these CAR-T cells were able to eliminate disease burden and significantly enhance survival as compared to control groups. These positive preliminary results indicate biological activity and are suggestive of potential therapeutic effect for the treatment of AML.

Laurence Cooper, M.D., Ph.D., Chief Executive Officer of ZIOPHARM Oncology commented, "As we progress through the remainder of 2016 with our Intrexon Corporation and MD Anderson collaborators, we believe our clinical stage assets and promising preclinical pipeline will position the company at the forefront of those utilizing the immune system in a controlled manner to combat cancer." Dr. Cooper added, "We believe that our CD33 CAR-T cell approach has the potential to positively impact a disease area that has been largely unexplored with this type of immune-therapy and overall this malignancy has seen inadequate improvement in treatment options. We look forward to moving into the clinic as soon as possible to help patients with advanced AML urgently in need of new therapies."

This planned Phase I trial will add to ZIOPHARM’s three active trials at leading institutions, two employing controlled gene therapy to express a powerful anti-cancer effector in interleukin-12 and the other incorporating the innovative non-viral Sleeping Beauty gene delivery system in CAR-T cell therapy for advanced lymphoid malignancies. This new program targeting CD33 is part of the Exclusive Channel Collaboration with Intrexon and is the next CAR-T target the companies are pursuing in addition to the first two targets already selected by the biopharmaceutical division of Merck KGaA.

ZIOPHARM intends to further expand its clinical programs in the area of natural killer (NK) cells and a combination approach to its Ad-RTS-hlL-12 gene therapy using an immune checkpoint inhibitor through the remainder of 2016. Additionally, ZIOPHARM and Intrexon continue to advance preclinical efforts leveraging the Sleeping Beauty platform, the clinical-stage RheoSwitch (RTS), and improving cell manufacturing for the clinical applications of T cells engineered to express CAR and TCR, as well as off-the-shelf approaches.