Deal Watch: Zymeworks Adds Daiichi To List Of Partners In I-O Cross Collaboration

Amgen gets into RNAi for cardiovascular indications with Arrowhead deal. Lilly and J&J out-license preclinical candidates, for epilepsy and cancer respectively, to smaller firms Cerecor and Tracon.

Scrip regularly covers business development and deal-making in the biopharmaceutical industry. Below is a roundup of some of the most noteworthy transactions that occurred between Sept.23-30. Deal Watch is supported by deal intelligence from Strategic Transactions.

Canadian biotech Zymeworks Inc. and Japan's Daiichi Sankyo Co. Ltd. announced a cross-cutting cancer alliance Sept. 28 that will focus on immuno-oncology. Under the deal, the two companies will cross-license assets from one another and collaborate on drug development efforts.

The deal marks the Vancouver-based company's fifth pharma partnership, following pacts with Merck & Co.Inc. in 2011, Eli Lilly & Co. in 2014, and both Celgene Corp. and GlaxoSmithKline PLC in 2015. (Also see "Zymeworks, GSK Sign Antibody Deal For Up To $440m" - Scrip, 4 Dec, 2015.) Under the agreement, Daiichi will acquire a license to Zymeworks’ Azymetric and Effector Function Enhancement and Control Technology (EFECT) platforms to develop a bispecific antibody therapeutic. In exchange, Zymeworks receives an upfront technology-access fee and research support.

Zymeworks will also be eligible to earn preclinical, clinical and commercial milestones, as well as up to double-digit tiered royalties on global product sales. Additionally, the biotech will license immuno-oncology antibodies from Daiichi, with the right to research, develop and commercialize multiple bispecific products globally in exchange for royalties on product sales. Specific financial details were not disclosed.

Amgen Licenses RNAi Cardiovascular Assets From Arrowhead

Arrowhead Pharmaceuticals Inc. is partnering two of its RNAi cardiovascular disease therapies in a deal announced Sept. 29 with Amgen Inc.

Amgen gets exclusive global rights to develop and commercialize Arrowhead's preclinical ARC-LPA program (AD01765) aimed at reducing lipoprotein(a), which has been genetically linked with increased risk of atherosclerotic cardiovascular disease independent of cholesterol and LDL levels. [See Deal] Amgen also receives an option to license exclusive worldwide rights to an RNAi therapy for an undisclosed genetically validated cardiovascular target.

Meanwhile, Arrowhead receives $35m up front, up to $617m in option payments and development, regulatory and sales milestone payments, plus low double-digit sales royalties (Strategic Transactions assumes as much as 30%) for the ARC-LPA project and single-digit royalties for the undisclosed program. Amgen also agreed to buy $21.5m in Arrowhead equity (3m shares at $7.16 each). Both compounds under the agreement are the first Arrowhead projects to incorporate its subcutaneous RNAi delivery platform.

In a Sept. 29 note, Leerink Partners analyst Geoffrey Porges pointed out that the deal follows a strategy used previously by Amgen. "These programs are very early, and are not material to Amgen’s outlook, but they are important indicators of the company’s strategy," he said. "Amgen has a history of acquiring pipeline cardiovascular therapies through backend-payment loaded transactions to build their metabolic disease portfolio from their existing (small) anti-PCSK9 antibody platform."

Cerecor Obtains Preclinical Epilepsy Candidate From Lilly

Lilly granted Cerecor Inc. exclusive global rights on Sept. 26 to develop and sell LY3130418, a preclinical transmembrane AMPA receptor regulatory proteins (TARP)-y8-dependent AMPA receptor antagonist for epilepsy.

In exchange for the rights, Cerecor pays $750k up front, $1.25m after the first patient is dosed in a multiple-ascending-dose study and up to $67.5m in additional development and sales milestones, plus mid-single to low-double digit royalties. [See Deal] Cerecor renamed the compound CERC611 and expects to begin Phase I trials in 2017.

Traditional AMPA receptor antagonist therapies are successful at down-modulating excitatory neurotransmission and reducing seizure activity in cases of epilepsy, but because of their broad range of activity in the nervous system, such treatments cause adverse effects including dizziness, ataxia, sedation or falls. TARP-y8-dependent AMPA receptor antagonists selectively modulate AMPA receptors found in the hippocampus, treating seizures locally without affecting synaptic transmission and causing unwanted side effects.

The addition of CERC611 will bring Cerecor's development pipeline total to three clinical candidates; it is also working on CER301 in Phase II trials for depression and CERC501 in Phase II for smoking cessation.

Tracon Licenses Pair Of Preclinical Cancer Compounds From Janssen

Janssen Pharmaceuticals Inc. licensed Tracon Pharmaceuticals Inc. rights to develop, manufacture and commercialize two preclinical cancer compounds – JNJ63576253 (renamed TRC253), an inhibitor of wild type androgen receptor (AR) and multiple AR mutations aimed at prostate cancer; and JNJ64290694 (TRC694), an inhibitor of NF-kB inducing kinase (NIK) for treating hematologic malignancies including myeloma.

As part of the agreement announced Sept. 28, Johnson & Johnson Development Corp. will make a $5m equity investment in Tracon, buying 840k shares at $5.95. [See Deal] With respect to TRC253, Janssen retains an option, exercisable until 90 days after Tracon demonstrates proof-of-concept, to regain exclusive rights to the program. Should it exercise the option, Janssen would pay $45m, up to $137.5m in regulatory and commercial milestones and low-single-digit royalties. If the option isn't exercised, Tracon could receive global rights and pay up to $45m in development and regulatory milestones and low-single-digit royalties.

For TRC694, Janssen additionally has rights, also exercisable until 90 days after Tracon demonstrates proof-of-concept, to negotiate for six months for a reversion of the related rights in the licensed intellectual property and to obtain an exclusive license to commercialize the NIK program. If not exercised, Tracon will retain rights and pay Janssen up to $60m in development and regulatory milestones and low-single-digit sales royalties. TRC253 has completed IND-enabling studies and Tracon anticipates commencing a Phase I/II trial in the first half of 2017. Tracon expects to file an IND for TRC694 during 2018.

Bluebird, Medigene Will Collaborate On TCR Therapies Against Four Targets

Medigene AG and bluebird bio Inc. agreed Sept. 29 to work together on the discovery and development of T-cell receptor (TCR) immunotherapies against four undisclosed cancer targets. [See Deal] Medigene will use its TCR isolation and characterization technology to generate and deliver TCRs to bluebird, which contributes its lentiviral vector, genome editing and synthetic biology platforms and its manufacturing expertise.

The partners will jointly conduct preclinical studies, after which point bluebird is responsible for all clinical development and global commercialization; it also gets an exclusive license for any intellectual property covering the discovered TCRs. Medigene gets $15m up front, R&D funding and could earn up to $1bn in pre- and post-sales milestones, plus up to double-digit royalties. The deal is the first commercial agreement for Medigene around its TCR technology.

Celgene Opts In On Abide Neurology Candidate

Celgene exercised its option on Sept. 29 to obtain ex-US rights to Abide Therapeutics Inc.'s ABX-1431, a first-in-class endocannabinoid system modulator, for the potential treatment of neurological diseases. The decision follows a February 2014 agreement between the companies in which Abide received $50m up front. [See Deal]

Focused on developing medicines targeting serine hydrolases (a large enzyme class), Abide will retain US rights to ABX-1431 and carry out various Phase Ib studies assessing its therapeutic potential in cannabinoid-sensitive diseases, neuromyelitis optica (NMO) and movement disorders. The biotech will receive a $20m exercise fee from Celgene, with the latter responsible for developmental cost for all indications from Phase III trials and further.

ABX-1431 is an orally active, selective, small-molecule inhibitor of monoacylglycerol lipase (MGLL) that controls levels of the endogenous cannabinoid, 2-arachidonoylglycerol (2-AG). This is said to regulate neurotransmitter balance, which links the drug to diseases such as multiple sclerosis (MS) and inflammatory conditions. The drug was well tolerated with no serious adverse events in a recent placebo-controlled, first-in-humans Phase Ia study.

Bayer Partners With DelSiTech On Delivery Of Ocular Drugs

Bayer AG is joining forces with the Finnish drug delivery technology and drug development company DelSiTech Ltd. to tackle the challenge of successful ocular drug delivery. The German pharma signed a collaboration and technology license agreement Sept. 29 for the worldwide application of DelSiTech's Silica Matrix drug-delivery platform to some of Bayer's ophthalmology compounds.

Specific financial terms of the agreement were not disclosed, but Bayer will fund development and commercialization of the collaborative projects, while DelSiTech will be entitled to a number of development milestone payments and royalties on potential sales.

Boehringer And HCA Institute Initiate I-O Collaboration

Boehringer Ingelheim GMBH has teamed up with contract research group Sarah Cannon Research Institute, via a new strategic collaboration focused on combining their respective CRO and drug-development expertise to re-design and optimize cancer clinical trials. Based in Nashville, the institute is affiliated with Hospital Corporation of America.

This program announced Sept. 29 will study BI’s monoclonal antibodies BI 754091 (anti- PD-1) and BI 754111 (anti-LAG 3) for the combination treatment of various cancers with unmet medical needs including non-small cell lung cancer (NSCLC). The partnership will allow rapid patient enrollment in clinical trials through the CRO’s network across the UK and US.

The private German company had a busy week on the deal front. On Sept. 28, Boehringer announced a tie-up with ViraTherapeutics GMBH's oncolytic virus platform and lead candidate – an expansion of its immuno-oncology pipeline, in line with the company's stated strategy. (Also see "Boehringer Increasingly Looking Outside For Oncology Growth" - Scrip, 10 Aug, 2016.) But that strategy took a massive blow Sept. 30 when it announced it was returning rights to the third-generation EGFR inhibitor olmutinib, which was the lynchpin of its oncology plans.

You can read more about deals that have been covered in depth in Scrip in recent days below:

(Also see "Hanmi Does It Again - RAF Inhibitor Goes To Genentech In $910m Deal" - Scrip, 29 Sep, 2016.)	After a series of blockbuster licensing deals last year, South Korea’s Hanmi has struck another major alliance, this time licensing out a novel oral RAF inhibitor that will strengthen biosimilar-threatened Genentech’s oncology portfolio.
(Also see "Boehringer Gets Option To Buy ViraTherapeutics And Cancer Virus Therapy" - Scrip, 28 Sep, 2016.)	Boehringer Ingelheim agreed to pay up to €210m to investigate ViraTherapeutics' lead candidate, VSV-GP, alone and in combination, with an option to buy ViraTherapeutics depending on the outcome of Phase I studies.
(Also see "Surprise Boehringer Decision Turns Hanmi Investors’ Hopes To Despair" - Scrip, 30 Sep, 2016.)	Hanmi shares have gone on a wild roller coaster ride as bad news came after good. A day after it announced a huge licensing agreement with Genentech, the South Korean firm unveiled that Boehringer Ingelheim had decided to return rights to olmutinib, the EGFR inhibitor it licensed from Hanmi last July.
(Also see "Maruho Broadens Derma Horizons Through Dual Licensing Deals" - Scrip, 30 Sep, 2016.)	Mid-sized dermatology specialist Maruho Co. Ltd. has licensed in selected rights in Japan to a novel antibody from Chugai Pharmaceutical Co. Ltd. and in global markets to a Janus kinase (JAK) inhibitor developed by Astellas Pharma Inc.