On July 28, 2015 Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) and Sanofi reported that they have entered into a new global collaboration to discover, develop and commercialize new antibody cancer treatments in the emerging field of immuno-oncology (Press release, Regeneron, JUL 27, 2015, View Source [SID:1234506716]). As part of the agreement, the two companies will jointly develop a programmed cell death protein 1 (PD-1) inhibitor currently in Phase 1 testing and plan to initiate clinical trials in 2016 with new therapeutic candidates based on ongoing, innovative preclinical programs.

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"The field of immuno-oncology has shown the potential to dramatically improve outcomes for patients with certain types of cancer. However, the field is still in its very early days," said George D. Yancopoulos, M.D., Ph.D., Chief Scientific Officer, Regeneron and President, Regeneron Laboratories. "We believe the approaches most likely to deliver the best results to patients will combine multiple innovative therapies acting on different pathways and targets both in the tumor and the body’s immune response – and will precisely target these medicines to the right patient. The efficiency and power of our suite of technologies, such as VelocImmune and VelociGene, combined with our human genetics capabilities, uniquely positions the Sanofi-Regeneron Alliance to accelerate the development of potential new immuno-oncology treatment options for cancer patients."

Sanofi will make an upfront payment to Regeneron of $640 million, and the companies will invest
$1 billion for discovery through proof of concept (POC) development (usually a Phase 2a study) of monotherapy and novel combinations of immuno-oncology antibody candidates to be funded 25 percent by Regeneron ($250 million) and 75 percent by Sanofi ($750 million). The companies have also committed to equally fund an additional $650 million (or $325 million per company) for development of REGN2810, a PD-1 inhibitor. In addition, Sanofi will pay Regeneron a one-time milestone of $375 million in the event that sales of a PD-1 product and any other collaboration antibody sold for use in combination with a PD-1 product exceed, in the aggregate, $2 billion in any consecutive 12-month period. Finally, the two companies have agreed to re-allocate $75 million (over three years) for immuno-oncology antibodies from Sanofi’s $160 million annual contribution to their existing antibody collaboration, which otherwise continues as announced in November 2009. Beyond the committed funding, additional funding will be allocated as programs enter post-POC development.

"The Sanofi-Regeneron Alliance has demonstrated its ability to translate cutting-edge science into groundbreaking medicines for patients with serious needs," said Elias Zerhouni, M.D., President, Global R&D, Sanofi. "With more than eight years of successful collaboration between us, I am confident in our ability to advance these novel programs. In addition to PD-1, the collaboration brings together a range of validated, innovative preclinical programs that have unique potential to help patients either as monotherapy or in combination approaches."

The new agreement covers both monoclonal antibodies and new bi-specific antibodies, a variation of standard antibody therapeutics in which two distinct targets within the body can be bound by the same molecule, usually the cancer cell and an immune cell. Regeneron has developed a novel and flexible manufacturing platform that enables efficient production of bi-specific antibodies that are otherwise similar to natural antibodies. Beyond PD-1, other programs in preclinical development include antibodies to lymphocyte-activation gene 3 (LAG3), glucocorticoid-induced tumor-necrosis-factor-receptor-related protein (GITR) and a programmed death ligand (PD-L1) inhibitor. Finally, the collaboration is advancing bi-specific antibodies that target hematologic and solid cancers, either as monotherapies or in combination regimens with other immune modulating treatments.

"Despite many advances over the last decades, cancer remains a leading cause of death and suffering around the world," said Israel Lowy, M.D., Ph.D., Vice President Clinical Sciences, Head of Translational Science and Oncology, Regeneron. "Although initial advances with immuno-oncology have helped certain patients, there is a tremendous opportunity to further unlock the potential of this new approach to help even greater numbers of people living with cancer."

The framework of the new immuno-oncology collaboration is as follows:

Regeneron will be responsible for discovery, antibody generation and development through POC, at which time Sanofi will have the ability to opt-in to further development and commercialization. In the existing antibody collaboration, Sanofi has the opportunity to opt-in at the time of an Investigational New Drug application (IND).

The companies will alternate serving as the lead development and commercialization organization after Sanofi opts-in to an antibody program.

For programs where Regeneron is the lead, including REGN2810, Regeneron will serve as the U.S. commercial lead, including recording U.S. sales, and the companies will equally fund post-POC development. Sanofi will record sales and serve as the commercial lead for all countries outside the U.S. Sanofi will retain the right to co-promote in the U.S. and Regeneron will retain the right to co-promote outside the U.S.

For programs where Sanofi is the lead, Sanofi will serve as the U.S. commercial lead and fund 100 percent of post-POC development, with Regeneron reimbursing up to 50 percent of such costs through the IO collaboration development balance, which represents the amount of development funding that Regeneron is obligated to repay out of its share of profits as described below. Sanofi will record sales and serve as the commercial lead for all countries outside the U.S. Regeneron will retain the right to co-promote in the U.S. and outside the U.S.

Sanofi and Regeneron will share equally in worldwide profits from sale of collaboration immuno-oncology antibodies.

As in the existing antibody agreement, Regeneron will repay the immuno-oncology collaboration development balance from its share of overall profits of the immuno-oncology antibodies, in an annual amount equal to 10 percent of the Regeneron share of profits.

The exclusive collaboration to discover and develop potential monotherapy or novel combination immuno-oncology antibody candidates through POC will last five years with an ability to extend the collaboration for selected ongoing programs for an additional three years. The agreement does not include Chimeric Antigen Receptors. Additional terms, including potential therapeutic targets or mechanisms, were not disclosed.

On July 28, 2015 Boehringer Ingelheim and Hanmi Pharmaceutical Co. Ltd reported an exclusive license and collaboration agreement for the development and global commercialisation rights, except South Korea, China and Hong Kong, of HM61713, a novel 3rd generation EGFR targeted therapy for the treatment of EGFR mutation positive lung cancer (Press release, Boehringer Ingelheim, JUL 27, 2015, View Source [SID:1234506712]). Under the terms of the agreement Hanmi will receive an initial payment of USD 50 million and is entitled to potential milestone payments of USD 680 million plus tiered double-digit royalties on future net sales. The agreement is subject to clearance under the Hart-Scott-Rodino Antitrust Improvements Act, similar requirements outside the U.S., and other customary closing conditions.

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Dr Jörg Barth, Corporate Senior Vice President, Therapy Area Head Oncology, Boehringer Ingelheim said, "This exclusive license agreement with Hanmi Pharmaceutical is a significant step towards our vision of providing a wide-range of lung cancer treatment options as we better understand the underlying drivers of this devastating disease. The in-licensing of a 3rd generation EGFR agent bolsters our existing lung cancer portfolio and reiterates our commitment towards improving the lives of people with cancer through innovation and tailored treatment options."

HM61713 is a novel 3rd generation, orally active, irreversible EGFR mutation selective tyrosine kinase inhibitor (TKI). At this year’s ASCO (Free ASCO Whitepaper) Annual Meeting, interim results of the Phase I/II clinical trial were presented and showed strong efficacy signals, combined with a favourable safety profile.1 The compound is currently in Phase II clinical development for patients with non-small cell lung cancer (NSCLC) with T790M mutations who have developed resistance to previous EGFR targeting agents. Preparations have begun for a broader Phase III trial programme, to be initiated in 2016.

HM61713 is another important pillar in Boehringer Ingelheim’s global lung cancer franchise which builds on two products, GIOTRIF/GILOTRIF (afatinib*) and VARGATEF (nintedanib**), approved in various countries. With the inclusion of HM61713, Boehringer Ingelheim now has more than 10 compounds in clinical development in a wide variety of oncology indications, including immune oncology approaches like an mRNA based therapeutic vaccine under development in collaboration with CureVac.

Dr Jeewoong Son, Chief Medical Officer of Hanmi Pharmaceutical said, "We are excited at the potential this license agreement with Boehringer Ingelheim will bring to the successful development of HM61713 and the possibilities this will offer to lung cancer patients. Boehringer Ingelheim has significant expertise in the field of lung cancer, specifically in EGFR mutated disease. Boehringer Ingelheim’s strong pipeline demonstrates its long-term commitment to successful development of cancer treatments. We are confident we have found the right partner to make the potential of HM61713 a reality."

On July 27, 2015 Teva Pharmaceutical Industries Ltd. (NYSE and TASE: TEVA) reported that it has withdrawn its cash and stock proposal to acquire all of the outstanding ordinary shares of Mylan N.V. (NASDAQ: MYL) and Teva does not intend to continue to pursue a transaction with Mylan at this time (Press release, Teva, JUL 27, 2015, View Source;p=RssLanding&cat=news&id=2071089 [SID:1234506710]). Teva’s decision to terminate the proposal to acquire Mylan follows today’s announcement that Teva has entered into a definitive agreement with Allergan to acquire Allergan Generics.

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"In light of our strategic acquisition of Allergan Generics, which will transform the industry, our Board and management team has decided that withdrawing the proposal to acquire Mylan is in the best interests of Teva stockholders," said Erez Vigodman, President and CEO of Teva. "Since announcing the proposal to acquire Mylan on April 21, 2015, we have appreciated the opportunity to talk with many of our investors about the future of the generics industry, and we are confident our proposed transaction with Allergan best positions Teva to succeed in today’s industry landscape."

Mr. Vigodman continued, "We continue to believe that a combination of Teva and Mylan would have made sense for our companies, our respective stockholders and the healthcare industry as a whole. However, despite our clear commitment to consummating a transaction, and our conviction that we ultimately would have succeeded in acquiring Mylan, we believe we have an even greater opportunity to create compelling, sustainable value for Teva’s stockholders through our transaction with Allergan – and we acted quickly to seize the opportunity. Our agreement with Allergan will reinforce Teva’s strategy to create an even stronger business model in the industry and will position us well to grow the business and better serve our customers and patients."

Teva intends to review its options with respect to its ownership of approximately 4.6% of the outstanding ordinary shares of common stock of Mylan.

Barclays and Greenhill & Co. are serving as financial advisors to Teva. Sullivan & Cromwell LLP, De Brauw Blackstone Westbroek N.V. and Tulchinsky Stern Marciano Cohen Levitski & Co are serving as legal counsel to Teva.