Regeneron stays out of ADC deal fray as in-house scientists tinker

Regeneron is pretty good at making antibodies. It’s kind of its thing. But, while the industry has gone deal crazy for antibody-drug conjugates (ADCs), the company has stayed out of the limelight.

That’s because, like most things at the physician-scientist-led biotech, the ADC work is being done in house.

“Antibody-drug conjugates require a level of expertise beyond antibody production. So we are, I would say, as good as anyone else in terms of developing regular antibodies or bispecific antibodies. We have made a commitment to developing an ADC platform in house,” said Israel Lowy, M.D., Ph.D., senior vice president of clinical sciences and head of translational science and oncology at Regeneron, in an interview. 

Regeneron is already working on one ADC using a different formulation of an early-stage med. REGN5093 is a METxMET bispecific that targets the MAP receptor and is currently in phase 1/2 testing for non-small cell lung cancer (NSCLC). Results showcased at the European Society of Medical Oncology in September 2022 showed six partial responses out of 36 patients who had received the highest dose of the naked antibody. Five of those patients had received prior anti-PD-1 treatment. The company at the time said that the data supported exploration of further combination options.

The ADC format, nicknamed REGN5093-M114, is in a phase 1/2 study. Regeneron is looking to pair that up with other meds in its stable to boost the activity in lung cancer. So far, the “naked antibody” paired with a conjugate has shown “intriguing activity” in advanced patients, Lowy says.

But then there’s a whole new ADC platform coming down the line, which, according to Lowy, will create an entirely new type of the engineered antibodies. Lowy hopes to have candidates from the new platform moving into the clinic “in the coming year or so.”

“We are building something internally. It's early days, so we will see how it turns out. We have high hopes for it,” Lowy said.

Regeneron’s “very busy and creative preclinical science group” came up with some ideas for new linkers and how to modify some of the active payloads in an ADC.

“They've been tinkering around in the background, and they've come up with some promising technologies. So we're hoping to bring it forward,” Lowy said “All these things always take time.”

He remembers Regeneron’s bispecific antibody research began 15 years ago, as the scientists worked on ways to establish efficacy and streamline manufacturing. Lowy does not see the ADC platform taking that long, however.


To deal or not to deal?

Meanwhile, Regeneron’s peers have been going all in on ADCs. Bristol Myers Squibb, GSK and Merck & Co. have all made major deals in the space. Merck took the biggest plunge by far, paying $4.5 billion upfront and $22 billion overall down the line to work with Daiichi Sankyo in October. 

That kind of dealmaking is not in Regeneron's plans, however. 

“We’re not about to—at least today—acquire another ADC company and try to bring it in house,” Lowy said. He declined to speak directly to the Daiichi deal, but said: “We talk to people all the time. There's never been a compelling case that was made to us that led us to do that to date.”

There have also been a few signs of oversaturation, as ADC-focused Pyxis Oncology cuts staff and programs. BMS, also wheeling and dealing, put down just $100 million for a partnership with Orum Therapeutics

An acquisition is not always the key to success, as AbbVie found with the $5.8 billion takeover of Stemcentrx in 2016. The gem of the deal was the ADC Rova-T, which eventually flamed out in the clinic, leaving the pharma to record a massive $4 billion impairment charge in 2019. The company continues on with several ADCs in its pipeline.

During a third-quarter earnings call, AbbVie CEO Richard Gonzalez noted that the company was aware of the possibility of working with Daiichi. But AbbVie has also turned to its internal scientists to build out an ADC portfolio.  

“We believe we have what we need,” he said, referring to ABBV-400, an internally developed program currently in a phase 1 trial for patients with solid tumors.

Another company looking internally is AstraZeneca, Daiichi’s partner on the now blockbuster breast cancer ADC Enhertu. While the two companies have seen major success together, Susan Galbraith, Ph.D., executive vice president of oncology R&D at the pharma, told Fierce Biotech last month that the U.K. pharma is ready to develop its own prospects for the next phase of ADC work.

Lowy says there’s a lot of room for improvement in ADCs. While he acknowledges there have been breakthroughs in prolonged, durable responses and improved survival, the therapies can be tough on patients.

“At the end of the day, though, it is still a chemotherapy. Granted, the idea is to deliver this chemotherapy in a much more targeted fashion so that there's less systemic toxicity,” Lowy said. “It's hard to make them completely kind and gentle. At the same time, immunotherapy is not without its side effects also, so there's no free lunch.”

The promise in ADCs lies with combinations, which have become the standard in oncology care. Lowy believes that just as chemotherapy can combine with immunotherapy, ADCs will be able to as well.

“These aren't separate things that can't talk to each other,” he said.

Combinations have always been a big part of Regeneron’s portfolio. Lowy likens the ADC work to how the company differentiated in immuno-oncology early with anti-PD1s.

“People initially said, ‘Why are you chasing an anti-PD1?’ Well, because you need it to sort of build a combinatorial platform to begin with,” Lowy said.

The anti-PD-1, of course, is Libtayo, approved now for NSCLC, squamous cell carcinoma and basal cell carcinoma. The drug brought in $375 million in the U.S. for fiscal year 2022, one of Regeneron's biggest revenue generators behind Eylea and Dupixent.