'I don't have a checklist': Seagen CEO talks about his next stop, Pfizer deal and the ADC landscape

David Epstein’s short tenure as Seagen’s CEO will likely end soon with the antibody-drug conjugate specialist’s sale to Pfizer. After a rich career spanning companies of various sizes, Epstein is keeping an open mind about where he might head next.

“I will hopefully make new drugs somewhere else,” Epstein said in a recent interview on the sidelines of the American Society of Clinical Oncology's annual meeting. “I don’t know where that will be.”

Throughout his time in biopharma, Epstein has worn many hats. He’s known for building Novartis’ oncology unit and leading the Swiss giant’s larger global pharma business. He fostered startups for five years at Flagship Pioneering before taking the reins at Seagen in November.

Those roles have given him experience in almost every therapeutic area and in both drug development and commercialization. That kind of resume opens a lot of possibilities—although going back to Flagship isn’t his plan right now.

“I want to see interesting science that can substantially improve people’s lives,” Epstein said of his ideal future role. “I’d want to work with people that have that same desire and goal and where I can help people be successful. And that could be anywhere, any location—doesn’t really matter to me.”

“I don’t have a checklist,” Epstein added. “I just have to see what’s available, and there’s no rush,” Epstein said, noting that he didn’t originally identify Seagen as a potential career stop.

The timing of Epstein’s appointment and the subsequent Pfizer merger agreement might have created the impression that the longtime Novartis exec was recruited to strike a sale after Merck bowed out. But Epstein said that wasn’t the case.

“One can’t just wish to sell a company, and then magically, it happens overnight,” Epstein said. 

Seagen wasn’t sending pitches to potential buyers at the time, Epstein noted. Instead, it was Pfizer CEO Albert Bourla who reached out to Seagen Chairman Felix Baker, Ph.D., after the J.P. Morgan Healthcare Conference in January and expressed Pfizer’s renewed interest in Seagen.

When Baker interviewed Epstein for the Seagen CEO job, he asked the candidate how he’d expand Seagen’s marketed portfolio, develop next-generation antibody-drug conjugates (ADCs) and take them global, all while building Seagen into a world-class oncology company, Epstein said.

“The main focus was to make sure I was committed to the long term,” he said.

But after taking the Seagen CEO job in November, Epstein helped execute the Pfizer sale in March. He collected a $57.5 million pay package during his short time at Seagen last year, a securities filing recently showed.


Why Pfizer?


Pending the close of the sale to Pfizer, Seagen’s long-term value will lie in the hands of the New York drug giant. As Epstein sees it, becoming part of a large pharma company like Pfizer should provide a tailwind as Seagen continues to grow.

For example, Pfizer can immediately expand Seagen’s portfolio worldwide and add new manufacturing and R&D capabilities, Epstein said.

“It’s almost like they fulfill your wishes in terms of what you would like to do on your own but [you] get it overnight instead of having to take a decade to build up,” he said.

Seagen would have struggled to build a commercial infrastructure beyond the 17 countries that it’s already in, Epstein said. With Pfizer, the ADC portfolio will immediately benefit from a global presence.

Besides, Seagen’s HER2 small-molecule drug Tukysa and RemeGen-licensed HER2 ADC disitamab vedotin could benefit from Pfizer’s experience with CDK4/6 breast cancer drug Ibrance. And Pfizer’s knowledge in genitourinary cancer, thanks to its Astellas-partnered prostate cancer drug Xtandi, is relevant for Seagen’s bladder cancer med Padcev.

Scale matters for R&D, too, the CEO said.

In the ADC world, AstraZeneca and Daiichi Sankyo recently grabbed the limelight with Enhertu. Pfizer could help Seagen level the playing field from a clinical development perspective, Epstein figures.

“If you look at the scale, the number of their phase 3 programs that [they] run in parallel … the fact that they can do that, they can enroll patients globally ... it will get harder and harder to compete as a smaller, mid-sized company,” Epstein said while comparing Seagen with the AZ-Daiichi partnership. “Pfizer immediately will bring strength to Seagen’s portfolio.”

Epstein raised Pfizer’s BCMAxCD3 bispecific antibody elranatamab as one example. While the drug’s initial indication in triple-class refractory multiple myeloma is under FDA review, Pfizer has simultaneously started three phase 3 trials in earlier treatment settings.

“That’s an example of something we could never do. We can do that for one drug, maybe. They can do it across our portfolio,” Epstein said.

On the drug discovery front, Epstein said he admires Pfizer’s chemistry capabilities.

“If I can deploy … Pfizer’s chemistry skills, combine it with our biology, we will make better ADCs more quickly,” Epstein said.


Seagen's ADC footprint


Seagen’s existing ADC programs have their share of competitors. For disitamab vedotin, the obvious competitor is Enhertu. But because the two drugs use different chemotherapies as their cancer-killing payloads, Seagen is positioning its med for use sequentially behind Enhertu. That Enhertu-relapsed setting is still a blockbuster opportunity, according to Epstein.

Meanwhile, CD30-targeted Adcetris, currently Seagen’s top-selling drug, is under threat from Bristol Myers Squibb’s PD-1 inhibitor Opdivo. A phase 3 recently showed that Opdivo was better than Adcetris at staving off cancer progression in newly diagnosed stage 3 or 4 classical Hodgkin lymphoma, according to data presented at ASCO 2023.

But the trial has yet to show whether Opdivo extends patients’ lives, which is the gold standard in evaluating a cancer drug’s efficacy. Adcetris, for its part, boasts the National Comprehensive Cancer Network’s highest recommendation because of a favorable overall survival showing against chemo. Besides, Seagen is exploring combining Opdivo with Adcetris and has already shown some encouraging tumor response data, Epstein noted.

Padcev, used in combination with Merck’s Keytruda, looks on track to replace Adcetris and become Seagen’s best-selling drug after a recent FDA accelerated approval in patients with newly diagnosed bladder cancer that’s ineligible for cisplatin-based chemotherapy.

Looking forward, the phase 3 EV-302 trial, which tests the combo in first-line patients regardless of their cisplatin eligibility, will likely determine the full extent of Padcev’s commercial potential. That study is expected to read out later this year.

Seagen also has ladiratuzumab vedotin, a LIV-1-targeted ADC that’s partnered with Merck.

As for drugs that Seagen has full control in the U.S., the company has identified three priority pipeline programs: disitamab vedotin for stomach and breast cancers, integrin beta-6-directed SGN-B6Aa for non-small cell lung cancers and other tumor types, and an anti-B7-H4 candidate for breast and gynecological cancers.

Moving forward, Epstein predicts that ADCs will become more effective and less toxic and that they will be used earlier in treatment sequences and in more combinations.

“In many places where standard chemo is used will be replaced with ADCs and patients will have longer lives because of it,” Epstein said. “That’s partially where we’re gonna go in this field.”

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