BARCELONA — In the span of 30 minutes, 29-year Merck veteran Eliav Barr can analogize drug development dealmaking to Reese’s candy, call himself an “old fart” when asked about career plans, get real about the flood of ADCs and explain why subcutaneous forms of big medicines, like Keytruda, are “quite sexy” for patients.
Eliav BarrHe also answers questions about the Summit Therapeutics data that everybody is talking about and lays out a vision for a bold claim: revolutionizing the treatment of small cell lung cancer.
Endpoints News caught up with the Merck Research Laboratories chief medical officer on the sidelines of the annual European Society for Medical Oncology congress in Spain. Below are highlights from the interview.
Subcutaneous Keytruda is on the horizon: In the days leading up to ESMO, Roche nabbed the first FDA approval for a subcutaneous PD-(L)1 inhibitor. It marked a key moment for patients, giving them an easier-to-use option for the immunotherapy class.
Merck will play catch up and release KEYNOTE-D77 data on its under-the-skin version of Keytruda later this year or in early 2025, Barr said. The drugmaker expects “two flavors” of the subcutaneous version: dosing every three or six weeks.
Going from an infusion to an under-the-skin delivery is “quite sexy” for patients because it’s a quicker treatment and can be done outside a cancer center, meaning patients don’t have to expose themselves to “all the bugs in the hospital” and the dreary associations that come with visiting a cancer facility, Barr said.
Summit has ‘some unknowns yet’: It feels like everyone has been talking about the Keytruda-topping data from Summit Therapeutics and Akeso’s ivonescimab, a bispecific antibody targeting PD-1 and VEGF. But the data, from a study in China, will have to bear out in additional studies before the medicine can head to the FDA for approval.
Barr said it will be a “race between efficacy and toxicity” given the history of side effects seen with VEGF inhibitors. “Can you create a molecule that provides the VEGF effect but doesn’t end up with toxicity that causes more harm than good,” he said. VEGF inhibitors can lead to hypertension among a long list of other toxicities.
“If you look at the data that they’ve shown so far, they’ve shown some really exciting data, but where there’s somewhat less efficacy, you start to see that catch up with the toxicity, or at least what seems like it,” Barr said.
More work needs to be done on ivonescimab. “But if it works, it’s going to be really important,” he added.
Big plans in small cell lung: Merck is relatively new to the area of small cell lung cancer, which comprises about 10% to 15% of all lung cancers. But the company now has two big shots on goal for the disease in which patients have a much lower five-year survival rate than those with non-small cell lung cancer.
As Merck partnered on Daiichi’s ADC candidate I-DXd, which is now in Phase 3, another mechanism of action for small cell lung cancer caught the eyes of Barr. Data on Harpoon Therapeutics’ T cell engager in the same disease led him to think: “‘Chocolate? Peanut butter? Mmm, Reese’s.'”
“So I told our business development [team], ‘Go fetch me that drug,’ and so we did,” Barr said.
Merck paid $680 million earlier this year to acquire Harpoon. A few months later, Merck said Daiichi would help it develop the T cell engager.
“Daiichi looked at the data and said, ‘Wow, that’s really cool,'” Barr said. “We said, ‘Well if you want to help us with that, that would be really good because then we’d both have the same stake in the two drugs so everyone is working toward the same goal.'”
With the two drugs, Barr said he hopes “we can revolutionize small cell [lung cancer] therapy, hopefully, get it to where we have it in non-small cell lung cancer, where we started off with single-digit five-year survival and now it’s triple of that.”
Further bets on T cell engagers: After Harpoon, Merck doubled down on T cell engagers with a $700 million upfront acquisition of a CD3 x CD19 bispecific antibody from Curon Biopharmaceuticals. It will investigate the medicine’s potential in lupus and other autoimmune diseases as well as cancer, Barr said.
Research on CAR-T cell therapies in autoimmune diseases has propelled the field in recent quarters, but Barr said T cell engagers are “sure as hell more scalable.”
A publication in the New England Journal of Medicine earlier this month also showed the potential of a BCMA-targeted T cell engager having “CAR-T like responses” in autoimmune patients, Barr said.
“What is a real serendipity — I can’t say that I knew this, but I’ll take luck when I get it — Harpoon has a BCMA T cell engager,” Barr said. “Now we can do a bake-off between the two and see which one is going to be the best one for which kinds of patients.”
‘Keep going shopping’: Merck has made a few acquisitions this year and is “always looking,” Barr said. The company is looking across multiple therapeutic fields. It made a big return to ophthalmology with its up to $3 billion EyeBio purchase in May. The companies quickly moved into late-stage testing this month.
“We keep looking. It has to be something that’s really different, transformational,” Barr said. “That’s why we went to T cell engagers. There’s a limit on how many ADCs you’re going to get at this point.”
No plans to leave: Multiple medical and science executives have departed or announced plans to leave large pharmaceutical companies this year, including Pfizer, Sanofi, AbbVie, Gilead and others. But Barr doesn’t plan to leave behind Merck.
“I’m happy. I’m an old man. I like where I sit,” Barr said, confirming he’s not going anywhere else. “I’d love to be able to say I’m young and moving on, but I’ve got a few more years to go.”