Deal Watch: Seattle Genetics And Genmab Partner Again On Anti-Cancer ADC

MabVax to provide antibody-targeting technology to Memorial Sloan-Kettering, which could yield CAR-T therapeutic candidates for which Juno Therapeutics will hold an exclusive option. Mylan acquires injectable anticoagulant Arixtra from Aspen for $300 million, while Asterias will work with Cancer Research UK on non-small cell lung cancer program.

“The Pink Sheet” regularly presents commentary and perspective on key business deals. Here is a summary of the most noteworthy transactions that occurred between Sept. 6 and Sept. 12.

Seattle Genetics/Genmab

The latest collaboration between Denmark’s Genmab AS and antibody-drug conjugate (ADC) specialist Seattle Genetics Inc. contains a potentially lucrative option for the U.S. company – to decide whether to receive higher sales royalties in exchange for lower milestones if the research advances to Phase III.

In the collaboration announced Sept. 10, Genmab will use Seattle Genetics’ auristatin-based ADC technology as the warhead for its AXL-targeting human monoclonal antibody HuMax-AXL. AXL is a signaling molecule expressed on many different types of solid tumors, while auristatin is a clinically validated cytotoxin guided to tumors by the antibody.

Genmab will pay an upfront of $11 million for exclusive rights to use the ADC technology with HuMax-AXL, plus more than $200 million in milestone payments and mid-to-high single-digit royalties on worldwide net sales. But, just before the initiation of Phase III studies, Seattle Genetics holds an option to increase royalties to double-digits in exchange for a reduction in milestone payments. Seattle Genetics’ Natasha Hernday, VP for corporate development, called the arrangement a “compelling financial proposition” as the program advances.

The 2010 deal between the two companies on an ADC targeting tissue factor antigen, HuMax-TF-ADC, which is in Phase I for solid tumors, also contains an option for Seattle Genetics to decide to share costs and future profits instead of milestone payments and royalties. But the decision has to be made at the end of Phase I instead of the start of Phase III [See Deal].

There are around 40 ADCs in clinical development around the world, and more than 60% of those use Seattle Genetics’ technology – its first ADC, Adcetris (brentuximab vedotin) for Hodgkin lymphoma, was launched in the U.S. in 2011 (Also see "Seattle Genetics Will Test Oncology Pricing Acceptance With Adcetris" - Pink Sheet, 29 Aug, 2011.).

Juno Therapeutics/MabVax/Memorial Sloan-Kettering

Antibody discovery firm MabVax Therapeutics Inc. has partnered with the privately held immunotherapy company Juno Therapeutics Inc. and Memorial Sloan Kettering Cancer Center in a two-part deal to develop novel chimeric antigen receptor (CAR) T-cell therapeutics.

Under the arrangement announced Sept. 10, MabVax will provide MSKCC with antibody-targeting sequences from its human antibodies, which MSKCC will use to test early stage CAR T-cell therapeutics in vitro and in animals. Juno, meanwhile, gains an exclusive option to license any CAR T-cell therapeutics developed using the sequences provided by MabVax.

Juno has emerged as one of two leading start-ups in the development of CAR T-cell therapeutics, a field of research that is getting a lot of attention from investors and big pharma (Also see "Deal-Making, Financing Coalesce Around Promising CAR-T Space In Cancer" - Pink Sheet, 8 Sep, 2014.). The company has raised more than $300 million in two private financings this year [See Deal].

MSKCC is one of Juno’s original founders, along with Fred Hutchinson Cancer Research Center and Seattle Children's Research Institute. MabVax, which merged with oncology developer Telik Inc. in July, has developed a pipeline of fully human antibodies to 11 separate cancer targets overexpressed on solid tumors [See Deal].

Asterias/Cancer Research UK

Asterias Biotherapeutics Inc. has joined forces with the development and commercialization arm of British charity Cancer Research UK to progress the U.S. group’s immunotherapy treatment AST-VAC2 into clinical trials in non-small cell lung cancer. AST-VAC2 is a first-in-class cancer vaccine composed of dendritic cells from human embryonic stem cells that is designed to stimulate patient immune responses to telomerase, which is abnormally expressed in over 95% of human cancers.

No financial details were divulged about the pact, announced Sept. 11, under which Asterias will complete development of the manufacturing process for AST-VAC2. CRUK then will produce the vaccine and conduct the Phase I and Phase II clinical trials after which Asterias will have an exclusive first option to acquire the data. If Asterias declines, Cancer Research Technology Ltd., CRUK’s development and commercialization arm, then will have an option to obtain a license to Asterias’ intellectual property for developing and selling AST-VAC2 and related products, from which Asterias would receive a share of revenue.

AST-VAC2 was developed following successful early trials of a similar Asterias drug, called AST-VAC1, which was designed to treat acute myeloid leukemia and was also derived from patients’ own blood cells. Asterias believe the novel vaccine has a mechanism of action that likely is synergistic with other immunotherapies such as immune checkpoint inhibitors and therefore has broad applicability across multiple cancers (Also see "Spinal Cord Injury Product Makes Progress As Asterias Picks Up Where Geron Left Off" - Pink Sheet, 28 Aug, 2014.).

The trial of AST-VAC2 will evaluate the safety and toxicity of the vaccine, feasibility, stimulation of patient immune responses to telomerase and AST-VAC2, and clinical outcome after AST-VAC2 administration in patients with either resected early-stage, or advanced forms of lung cancer. The partners hope their collaboration will accelerate clinical studies of AST-VAC2 and the collection of proof-of-concept data for the entire human embryonic stem cells immunotherapy platform.

The collaboration will build on CRUK’s increasing interaction with big pharma in the hunt for drug innovation in the area of cancer. In April, the charity partnered with AstraZeneca PLC, Pfizer Inc. and Britain’s publicly funded National Health Service to conduct a groundbreaking clinical trial for patients with late-stage NSCLC by assessing the genetics of lung tumors to identify small groups of patients who, because of the specific genetic changes causing their cancer, are more likely to benefit from a certain drug (Also see "AstraZeneca, Pfizer, U.K. Charity’s Joint Lung Cancer Trial Aims To Make Tumor Genetic Testing Routine" - Pink Sheet, 16 Apr, 2014.).

Mylan/Aspen

Mylan NV added to its burgeoning injectables business Sept. 10 with the purchase of injectable anticoagulant Arixtra (fondaparinux sodium) from Aspen Global Inc. for a total of $300 million (Also see "Mylan Increases Injectable Presence, But In Declining Market" - Pink Sheet, 10 Sep, 2014.).

A Mylan subsidiary will acquire all U.S. commercialization rights to Arixtra, as well as the authorized generic version of the drug. Mylan already sells the branded version of the drug in the U.S. through a prior agreement with Aspen and Apotex Inc. currently sells the authorized generic. Those rights will transfer to Mylan by the end of the year. The Pittsburgh generic and specialty pharma will pay $225 million upfront, as well as $75 million in milestone payments.

The branded product brought in $18.8 million in 2013 U.S. sales, while the authorized generic generated more, about $95.3 million. Dr. Reddy's Laboratories Ltd. also markets a generic version of the drug, which brought in $68 million in sales last year.

Sales of the drug – in all three iterations – have been on the decline since 2012 when oral anticoagulant options entered the market, including Johnson & Johnson /Bayer AG ’s Xarelto (rivaroxaban), Boehringer Ingelheim GMBH ’s Pradaxa (dabigatran) and Bristol-Myers Squibb Co./Pfizer Inc. ’s Eliquis (apixaban) (Also see "New Eliquis And Pradaxa Filings Promise To AMPLIFY Competition In VTE" - Pink Sheet, 1 Jul, 2013.).

Calico/University of Texas Southwestern/2M Companies

Google-financed Calico Life Sciences LLC made its second deal in as many weeks Sept. 11, announcing a collaboration with University of Texas Southwestern Medical Center and 2M Companies around novel nicotinamide phosphoribosyltransferase (NAMPT) compounds that could offer utility in neurodegenerative disease. On Sept. 3, Calico agreed to a $750 million equity agreement with AbbVie Inc. that will help fund construction of facilities for the new biotech in the San Francisco Area (Also see "Deal Watch: Infinity Scores With AbbVie Deal, AbbVie Tries New Angle With Calico" - Pink Sheet, 8 Sep, 2014.).

UT Southwestern published research the week of Sept. 8 on compounds that target the energy metabolism enzyme P7S3, a process that has shown promise in animal models of neurodegeneration, including neurocognitive impairment, Parkinson’s disease, amyotrophic lateral sclerosis and depression. The school licensed those compounds to Dallas-headquartered 2M, which in turn has out-licensed development and commercialization rights for the program to Calico.

Kolltan/Xetrios

Connecticut-based Kolltan Pharmaceuticals Inc., which is focused on discovery and development of antibodies that target receptor tyrosine kinases, acquired privately held Xetrios Therapeutics Inc. on Sept. 9; deal terms were not disclosed. Founded in 2009 around Salk Institute for Biological Studies research into the TAM receptor tyrosine kinase family, Xetrios brings privately held Kolltan potential for addressing targets in oncology, autoimmune disease and infectious disease.

Having raised a $60 million Series D financing in March, Kolltan’s lead candidate is KTN3379, a novel antibody targeting the ErbB3 receptor tyrosine kinase (Also see "Kolltan Raises $60 Million Series D, But Keeps Mum About Cancer Program" - Pink Sheet, 28 Mar, 2014.). The antibody is in Phase I studies in solid tumors, the company says.