Merck has struck a deal to develop Seattle Genetics’ antibody-drug conjugate (ADC) ladiratuzumab vedotin. The agreement will see Merck pay $600 million and make a $1 billion investment in Seattle Genetics in return for the chance to embark on a joint development program.
News of the deal dropped within hours of Gilead’s statement about its $21 billion acquisition of another ADC player, Immunomedics. The centerpiece of that deal is Trodelvy, an anti-Trop-2 ADC that is under review at the FDA as a third-line treatment for metastatic TNBC.
Both Immunomedics and Seattle had a joint partnership a few years back, but the deal turned ugly and it was a wrenching split. In the end, it was Immunomedics which turned out to nab the big bucks buyout deal, while Seattle got the smaller biobucks pact with Merck.
Still, Merck doesn't usually make such hefty biobucks deals, so for Seattle, this is still a major outcome after killing off its Immunomedics pact. Ladiratuzumab vedotin is designed to deliver a microtubule-disrupting agent to cells that express the zinc transporter LIV-1. As LIV-1 is upregulated in triple-negative breast cancer (TNBC), and its expression is maintained after hormonal therapy, Seattle Genetics identified the transporter as a way to target tumor cells. Once in a cell, the ADC releases its payload, leading to cell cycle arrest and apoptosis.
Merck and Seattle Genetics began exploring the effect of combining the ADC and Keytruda in a phase 1/2 breast cancer trial a few years ago. Now, having seen early efficacy data, Merck has decided to play a bigger role in the program.
That decision could cost Merck a sizable sum. In addition to the $600 million upfront and $1 billion investment—which is priced 33% above Seattle Genetics’ close on Friday—Merck has committed to up to $2.6 billion in milestones.
Merck’s willingness to commit to those sums reflects evidence that, in addition to having direct cancer-killing power, ladiratuzumab vedotin can create a more favorable microenvironment for its big blockbuster Keytruda. The expectation is that the cell deaths caused by the ADC will make Keytruda more effective by increasing the tumor infiltration of activated T and NK cells.
Seattle Genetics shared evidence to support that hypothesis last year when it showed 35% of people with locally advanced or metastatic TNBC responded to first-line treatment with ladiratuzumab vedotin plus Keytruda. The vast majority of the responses were partial. The biotech is due to share more data from the trial this week.
Keytruda is closing in on FDA approval in some TNBC patients. Merck filed for approval on the basis of evidence that adding the checkpoint inhibitor to chemotherapy improves progression-free survival in patients with PD-L1–positive cancer. Seattle Genetics phase 1/2 didn’t select patients based on PD-L1 status, leading researchers to speculate the ADC may widen immunotherapy efficacy in TNBC.
Merck and Seattle Genetics plan to build on that early data by embarking on a joint development program that will test ladiratuzumab vedotin as a monotherapy and in combination with Keytruda in TNBC, hormone receptor-positive breast cancer and other LIV-1-expressing solid tumors. Melanoma, prostate, ovarian, uterine and cervical cancers are among the tumors associated with LIV-1.
The partners disclosed details of the ladiratuzumab vedotin deal alongside news of a smaller agreement covering tyrosine kinase inhibitor Tukysa. Merck is set to pay $125 million upfront and commit to up to $65 million in milestones for the exclusive license to the drug in Asia, the Middle East and Latin America. Tukysa is approved in certain metastatic HER2-positive breast cancers in the U.S., Switzerland, Singapore, Australia and Canada.