First of all, HeartMD, bulwnkl, britterock and Saul, mahalo for your appreciative comments and feedback on my macro CAR T-cell post.
In my ongoing due diligence, my main focus is now on CAR T-cell research and therapies that address tumor cancers, e.g., the ZioPharma/Intrexon/M.D. Anderson Cancer Center collaboration; and Dr. Steven Rosenberg at the National Cancer Institute, who planned to start clinical trails this year, based on his neoantigen research.
A 3/28/2017 post by Saul and response by bulwnkl were right on recognizing ZioPharm’s impending cash shortage prior to proceeding with the next pivotal Phase 3 trial.
ZioPharma related: After positive meetings with both FDA and European regulators, we are working to finalize the optimal pathway for our pivotal trial.
Details of the pivotal Phase 3 trial will be made available following evaluation and completion of discussions with clinical advisors as well as regulators…, to which Saul commented: Remember to not get overly excited. They still don’t have a marketable product and won’t for some time, and they are still burning cash..
Bulwnkl commented: my bunion is telling me that ZIOP is getting (or dang well better get) a partner or bought out in short order. Cash is drying up quickly.
Biotech sources also raised concerns that ZioPharma might have to seek a partner with cash resources.
Revisiting the ZioPharma, M.D. Anderson Cancer Center and Intrexon partnerships and agreements, I immediately found a major news release from both Intrexon and ZioPharma on 4/3/2017:
Intrexon and ZIOPHARM Oncology, in an exclusive partnership with Merck KGaA, Darmstadt, Germany, are advancing a unique approach to develop therapeutic candidates for two CAR-T targets expressed on a wide range of tumor types, including hematologic malignancies and solid tumors.
The distinctive methodology centers on two technologies: the proprietary RheoSwitch Therapeutic System® (RTS®) platform to regulate expression of membrane-bound interleukin-15 (mbIL15) co-expressed with CARs and Sleeping Beauty non-viral gene integration.
This is significant news because Merck KGaA who has been in the shadows while Phase 1 and 2 development efforts were completed by ZioPharma and Intrexon, is now stepping forward with a partnership with perhaps financial commitments (unrevealed) to support Phase 3 and other efforts. I see this as Merck giving its full endorsement and support of the RheoSwitch Therapeutic System platform and the Sleeping Beauty non-viral gene integration. Some here might be asking, "Who the heck is Merck KGaA?
Merck KGaA of Darmstadt, Germany, is a leading company for innovative and top-quality high-tech products in healthcare, life science and performance materials. The company has six businesses – Biopharmaceuticals, Consumer Health, Allergopharma, Biosimilars, Life Science and Performance Materials – and generated sales of € 15 billion (almost U.S. $16 billion) in 2016. Around 39,000 employees work in 70 countries to improve the quality of life for patients, to foster the success of customers and to help meet global challenges. Merck KGaA, Darmstadt, Germany, is the world’s oldest pharmaceutical and chemical company – since 1668, the company has stood for innovation, business success and responsible entrepreneurship. Holding an approximately 70% interest, the founding family remains the majority owner of the company to this day. Merck KGaA, Darmstadt, Germany holds the global rights to the Merck name and brand. The only exceptions are Canada and the United States, where the company operates as EMD Serono, EMD Millipore and EMD Performance Materials.
[Note: Not to be confused with Merck & Co., Inc. (NYSE: MRK), d.b.a. Merck Sharp & Dohme (MSD) outside the United States and Canada, which is an American pharmaceutical company and one of the largest pharmaceutical companies in the world with $39.8 billion revenue in 2016. The company was established in 1891 as the United States subsidiary of the German company Merck, which was founded in 1668 by the Merck family. Merck & Co. was nationalized by the US government during World War I and subsequently established as an independent American company in 1917. While it operates as Merck & Co. in North America, the original Merck based in Darmstadt holds the rights to the Merck name everywhere else.]
Back on 3/30/2015, Intrexon Corporation and Merck Serono, the biopharmaceutical business of Merck KGaA, Darmstadt, Germany, announced an exclusive strategic collaboration and license agreement to develop and commercialize Chimeric Antigen Receptor T-cell (CAR-T) cancer therapies. This collaboration advanced Merck Serono’s comprehensive, science-driven strategy to develop innovative therapies that modulate the immune system’s natural ability to fight tumors.
Intrexon was responsible for all platform and product developments until Investigational New Drug (IND) filing. Merck would nominate targets of interest for which CAR-T products would be developed. Merck would also lead the IND filing and pre-IND interactions, clinical development and commercialization. In addition, Intrexon had the opportunity to explore targets independently, granting Merck opt-in rights during clinical development.
Under the terms of the agreement, Intrexon received an upfront payment of $115 million. For the first two targets of interest selected by Merck Serono, Intrexon received research funding and was eligible to receive up to $826 million development, regulatory and commercial milestones, as well as tiered royalties on product sales. In addition, Intrexon was also eligible to receive further payments upon achievement of certain technology development milestones.
Intrexon, in turn, split the upfront $115 million with its partner ZioPharm.
Merck Serono is the biopharmaceutical business of Merck that discovers, develops, manufactures and markets prescription medicines of both chemical and biological origin in specialist indications. With headquarters in Darmstadt, Germany, Merck Serono offers leading brands in 150 countries to help patients with cancer, multiple sclerosis, infertility, endocrine and metabolic disorders as well as cardiovascular diseases. In the United States and Canada, EMD Serono operates as a separately incorporated subsidiary of Merck Serono.