DUBLIN – Shares in Genmab A/S gained 5% during trading on Nasdaq June 10 on news of an oncology alliance with Abbvie Inc., in which it is banking $750 million up front and up to $3.15 billion in development, regulatory and commercial milestones for up to seven next-generation antibody-based therapeutics.
The deal represents a big step for Copenhagen, Denmark-based Genmab in its grand strategy of launching a proprietary product in the U.S. by 2025. It has always been open to achieving that ambition with a co-commercialization partner. The alliance with Abbvie, of North Chicago, now provides it with multiple shots on goal, while at the same time providing it with the resources and capabilities to realize it.
“This is a strategic initiative,” Genmab CEO Jan van de Winkel told BioWorld. “We were convinced that we really needed a big machine for a number of our programs.” The alliance encompasses three existing programs and up to four others, which could emerge from a discovery collaboration. He initiated the dialogue with Abbvie about a year ago. It “basically checked all the boxes,” he said, in terms of its capabilities in oncology and its success at executing 50-50 deals – with the Genentech arm of Roche Holding AG on Venclexta (venetoclax) and with the Janssen Biotech arm of Johnson & Johnson on Imbruvica (ibrutinib).
Two of the Genmab programs are already in clinical development. Epcoritamab, which is based on its bispecific Duobody technology and targets the T-cell co-receptor CD3 and the B-cell receptor CD20 (CD3 x CD20), is undergoing a phase I/II trial in B-cell hematological malignancies. Duohexabody-CD37 (GEN-3009) is a bispecific IgG1 antibody, which combines dual targeting of the leukocyte antigen CD37 with Genmab’s Hexabody technology, which is designed to increase potency by promoting the assembly of antibody hexamers at the cell surface. The molecule is in phase I for hematological malignancies. The third disclosed program is a Duobody targeting CD3 and the 5T4 oncofetal antigen, for which Genmab filed a U.S. IND and multiple clinical trial applications in Europe during the first quarter. It has potential in multiple solid tumor indications.
Epcoritamab is the most advanced. Genmab disclosed phase I/II dose-escalation data in relapsed or refractory B-cell non-Hodgkin lymphoma at the virtual American Society of Clinical Oncology (ASCO) meeting last month, including an 86% overall response rate (ORR) in patients with follicular lymphoma and a 50% ORR in patients with diffuse large B-cell lymphoma or high-grade B-cell lymphoma, including three who had failed CAR T therapy.
Moving that program into phase III is an urgent priority. “One of the things that brought the two parties together was – is – a commitment to advancing the molecule as rapidly as possible,” Abbvie’s chief medical officer, Neil Gallagher, told analysts on a conference call Wednesday. “With respect to the potential for the molecule, we have been, with Genmab, observing excitedly the emerging data. We believe that the data, in terms of efficacy, are extremely robust.”
The phase III program will be comparable to that which Genmab’s partner, J&J, of New Brunswick, N.J., undertook to gain approval for Genmab’s CD38-directed blockbuster myeloma drug, Darzalex (daratumumab). “We will have a very broad and extensive program. We have already mapped it out together with Abbvie,” van de Winkel said on the call. “We hope to start at least one phase III before the end of this year and then multiple [studies] next year.” The pivotal program will include a number of combination studies, guided by preclinical data it has already obtained. Abbvie’s BCL-2 inhibitor, Venclexta, and its BTK inhibitor, Imbruvica, could feature in those studies. Epcoritamab’s immediate competitors are mosunetuzumab and REGN-1979, which are in development at Basel, Switzerland-based Roche and Tarrytown, N.Y.-based Regeneron Pharmaceuticals Inc., respectively.
Deal ‘makes strategic and financial sense’
The terms attached to epcoritamab differ from those attached to the other programs. Genmab will book sales of the drug in the U.S. and Japan, while Abbvie will lead commercialization in all other territories. Genmab will receive tiered royalties ranging from 22% to 26% on Abbvie’s net sales of the product.
For all other programs, the companies will share responsibilities for global development and commercialization in the U.S. and Japan, while Genmab retains co-commercialization options for all other territories. Each company will contribute antibody molecules and technologies, including antibody-drug conjugate (ADC) technologies, to the discovery collaboration. Genmab will carry the costs of the initiative through phase I development, at which point Abbvie can decide to opt in.
The latter four programs account for about $2 billion of the total biobucks, including option payments, attached to the deal. All kick in after phase I. Epcoritamab accounts for about half of the remaining $1.15 billion in development, regulatory and commercial milestones. “Around 60% out of the total $1.15 billion are clinical and regulatory,” Genmab’s chief financial officer, Anthony Pagano, said on the call.
Genmab’s other big play for its goal of becoming a “fully integrated biotechnology powerhouse” is the ADC tisotumab vedotin, which it is developing on a 50-50 basis with Seattle Genetics Inc., of Bothell, Wash. Phase II data in cervical cancer, which, van de Winkel said, are “potentially pivotal,” are expected late in the present quarter or early in the next.
For Abbvie, the deal is part of its general strategy of diversifying the business, which has long been overly dependent on its lucrative Humira (adalimumab) franchise. Its $63 billion acquisition of Dublin-based Allergan plc, which closed last month, was the main driver of that particular plot. But Mizuho Securities analyst Vamil Divan located that transaction – which “makes strategic and financial sense” – in the same context. “The deal also fits in strategically given the strong presence Abbvie already has in the hematological oncology space with Imbruvica and Venclexta,” he wrote in an investor note. Evercore ISI noted that the alliance looked to be “a decent deal” but, from an Abbvie investor perspective, “perhaps a bit pricey.” Time, as ever, will tell.