The ESMO ADC Files: Lilly, trying to avoid 'shiny new objects,' backs at least a small truck up anyway

Editor’s note: From the moment Merck & Co. announced a multibillion-dollar deal with Daiichi Sankyo on the first day of the European Society of Medical Oncology Congress, antibody-drug conjugates emerged as one of the major biotech headlines from the conference. Here, we present the ESMO ADC Files, with more on the ADC frenzy.

MADRID—Eli Lilly’s Jacob Van Naarden thinks his peers’ rush to snap up every antibody-drug conjugate (ADC) out there may be a little overblown.

“We as a field have a tendency to sort of see shiny new objects and then assume there's going to be a zillion more shiny new objects in the same class. And I actually think historically, that's not been true,” Van Naarden told Fierce Biotech on the sidelines of the European Society for Medical Oncology (EMSO) Congress in Madrid.

Van Naarden, who is president of Loxo@Lilly, likens the ADC frenzy to what happened in immunotherapy, with major companies chasing PD-1s. That breakthrough—led by Merck & Co.’s Keytruda and Bristol Myers Squibb’s Opdivo—revolutionized cancer care, no doubt, says Van Naarden.

He just thinks the industry should have been more particular about the candidates. Instead, biopharmas went all in trying to pick up every last PD-1 in development.

“Industry spent, what, tens of billions, maybe hundreds of billions of dollars, on immunotherapy to find the next PD-1, and that's largely not been a successful effort,” Van Naarden said. “So I think that we need to be careful as a field anointing classes of therapy instead of singular products or singular targets.”

Industry spent, what, tens of billions, maybe hundreds of billions of dollars, on immunotherapy to find the next PD-1 and that's largely not been a successful effort." — Jacob Van Naarden

At a conference where pharmas are jockeying for attention with flashing booths advertising their medicines, Van Naarden allowed that Enhertu, AstraZeneca and Daiichi Sankyo’s breast cancer and lung cancer med, “is amazing.” Astellas and Seagen also presented what he called a “transformative advance” for patients with bladder cancer for their ADC Padcev at ESMO.

But not all the data have been great in this class.

“There's other examples, actually, even at this meeting, of ADCs in registrational, phase 3 studies that I think are not that exciting, honestly,” Van Naarden said—withholding the names of those companies and drugs.

Jacob Van Naarden (Eli Lilly)

Lilly, he says, prefers to be modality-agnostic, picking and choosing the therapies that will have the biggest impact for patients.

“Across our entire portfolio, we take a very product-driven view of the world. In other words, do we like what this particular drug has the potential to do for these particular patients, almost regardless of the modality, and if we do then either we'll try and build one or we'll try and buy one if we could find what we like—versus, we believe in some whole new class that we're going to back up the truck on,” Van Naarden said.

“The theme for us is: I want the ability to be able to make medicines in all of these different classes,” he continued. “That's different than to say that the next wave of innovation is going to come entirely from one new thing. I don't really believe that to be true.”

Having said all that, Lilly still bought ADC biotech Mablink Bioscience earlier this month. The Big Pharma also had a PD-1, Innovent Biologics’ Tyvyt, which was once billed as a potential low-cost choice in a multibillion-dollar class. But the FDA ultimately rejected it in nonsquamous non-small cell lung cancer and reprimanded the partners for using China-only pivotal data that compared the experimental therapy to an outdated regimen.

What was it that made Van Naarden and co. back up at least a smaller truck to Mablink? The lead candidate is a folate-receptor-alpha-targeted ADC that uses a topoisomerase payload and a novel linker technology. He likens the therapy to ImmunoGen’s Elahere, which was approved for platinum-resistant ovarian cancer by the FDA in November, calling that move a “big advance for those patients.”

But Van Naarden thinks Lilly can do better with Mablink’s MBK-103, which he believes has a better payload and a better linker.

Lilly had previously worked with ImmunoGen through a deal struck in 2011 but ultimately cut the partnership seven years later. The two are working together once again through a $13 million upfront, $1.7 billion biobucks deal that was signed in February 2022. Mablink was also Lilly’s second ADC deal of the year, the first being the acquisition of Emergence Therapeutics in June.

With so much competitive interest in ADCs, it’s easy to imagine that biotechs in the space were inundated with phone calls and meeting requests from pharmas all over the world. That’s where Lilly has to be careful, Van Naarden says. Everyone can see the same public data, so if something is good, the price goes way up. At the end of the bidding, will there still be value in the program?

“Very little ends up being left to the imagination. If everyone sees the same thing, that means that more people are going to be running after it,” he says. “In other words, they're buying it for a fair price, versus getting value out of the deal.”

“We haven’t done, really, any of that,” Van Naarden says. Instead, Lilly has looked earlier, taking risks, like with Mablink and Emergence, which have preclinical products that are not yet being tested in humans.

“We can all sit around the table and disagree about whether or not we think it's going to work,” Van Naarden said. “That’s actually what creates value, because if I think it's going to work and you don't think it's going to work, that means that I'll show up at the bidding table, and you won't.”  

“Our strategy is to go earlier and take more risk and recognize that we're going to be wrong a bunch of the time,” he adds. “But that's OK.”