Janssen, Genmab Partner on Follow-On to Darzalex for Multiple Myeloma, Diffuse Large B-Cell Lymphoma

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Genmab’s HexaBody technology, illustrated on the company’s website, is a proprietary antibody platform designed to allow for the creation of potent therapeutics by inducing antibody hexamer formation after target binding at the cell surface. According to Genmab, HexaBody builds on the natural biology of antibodies (Figure 1) to form the antibody hexamers, which is critical for optimal binding of the first component of the complement cascade, C1 (Figure 2). This concept of targeted assembly of antibodies into hexamers at the cell surface can be applied to develop potentiated antibody therapeutics, specifically antibody molecules with a single point mutation to enhance hexamerization upon cellular target binding, thereby strengthening the antibody’s potency (Figure 3). [Genmab]

Johnson & Johnson’s Janssen Biotech has signed an exclusive worldwide license and option agreement with Genmab through which the companies plan to develop and commercialize a next-generation follow-on to their co-developed blockbuster multiple myeloma treatment Darzalex® (daratumumab).

The companies’ potentially more than $275 million agreement covers HexaBody®-CD38, a next-generation human CD38 monoclonal antibody product incorporating Genmab’s HexaBody technology.

Genmab has agreed to collaborate exclusively with Janssen on HexaBody-CD38, with Genmab agreeing to fund R&D activities until completion of clinical proof of concept studies in multiple myeloma and diffuse large B-cell lymphoma.

Based on data from those studies, Janssen may exercise its option and receive a worldwide license to develop, manufacture, and commercialize HexaBody-CD38.

Genmab’s HexaBody technology is a proprietary antibody platform designed to allow for the creation of potent therapeutics by inducing antibody hexamer formation after target binding at the cell surface—specifically by enhancing the assembly of antibody hexamers (clusters of six) after target binding at the cell surface. That results in enhancement of immune effector functions including complement-mediated killing (complement-dependent cytotoxicity (CDC)).

According to Genmab, its HexaBody technology can transform antibodies with limited or absent CDC into potent, cytotoxic antibodies.

Genmab said its agreement with Janssen follows promising preclinical data generated by Genmab for HexaBody-CD38 in a panel of multiple myeloma, lymphoma, and leukemia models

“Could be superior to dartumumab”

“Encouraging preclinical data suggest that HexaBody-CD38 could be superior to daratumumab for certain tumor cell types and may expand and extend the promise of CD38-targeted therapies for more patients with multiple myeloma, lymphoma, leukemia, and potentially beyond,” Genmab CEO Jan van de Winkel, PhD, said in a statement. “With this agreement, we hope to build upon the successful and productive relationship that we have established with Janssen.”

That relationship led in 2015 to FDA approval for Darzalex as the first human CD38 mAb to reach the market and the first mAb to receive the agency’s approval to treat multiple myeloma. Last year, Darzalex-related royalties and milestone payments from Janssen accounted for 75.8% of Genmab’s revenue, compared to 90% in 2017. Genmab recorded $90 million in milestone payments and DKK 1.708 billion (about $259 million) in royalties related to Darzalex sales in 2018.

Genmab disclosed its 2018 royalty figures last month when it filed for a $500 million U.S. initial public offering. In that filing, Genmab said it plans to offer American Depositary Shares on the Nasdaq Global Select Market under the symbol “GMAB.”

Under the companies’ latest agreement, Genmab would receive $150 million from Janssen if it exercises its option to co-develop HexaBody-CD38, as well as up to $125 million in payments tied to achieving development milestones. Genmab would also be eligible for a flat royalty rate of 20% on sales of HexaBody-CD38 until a specified time in 2031, followed by 13–20% tiered royalties on sales thereafter.

If Janssen does not exercise its option, Genmab can continue to develop and commercialize HexaBody-CD38 for Darzalex-resistant patients, and in all other indications except those multiple myeloma or amyloidosis indications where Darzalex is either approved or is being actively developed.

52% revenue jump projected

Genmab said the agreement will have no material effect on its 2019 financial guidance to investors. On February 20, Genmab projected it would generate DKK 4.6 billion ($697 million) in 2019 revenue, up 52% from DKK 3.025 billion ($458 million) in 2018.

Most of the revenue projected for this year is expected to consist of Darzalex royalties of DKK 2.685 billion (approximately $407 million), based on estimated net sales of $3.0 billion.

Genmab also expects to rack up Darzalex milestone payment of approximately DKK 1.5 billion ($227 million) related to commercial net-sales based milestones for achieving net-sales in a calendar year of both $2.5 billion and $3.0 billion, respectively.

The remainder of Genmab’s projected 2019 revenue consists of cost reimbursement income, milestone payments for pipeline candidates developed using Genmab’s DuoBody technology; and royalties from Genmab’s other marketed product Arzerra® (ofatumumab), indicated for certain types of chronic lymphocytic leukemia, and developed with and marketed by Novartis.

In 2012, Janssen agreed to license Genmab’s DuoBody technology platform to produce and develop bispecific antibodies with two different “arms” that bind to two different targets or different epitopes of the same target.

Using that technology, Janssen can create up to 20 DuoBody products for disease-target combinations in all therapeutic areas. The first product to be developed, JNJ-61186372, is designed to target EGFR and cMet, two validated targets for cancer.

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