As one of the first Big Pharmas to embrace antibody-drug conjugates (ADCs), Roche plans to make further bets on the popular cancer modality, according to the company's global head of pharma partnering, James Sabry, Ph.D. But biotechs looking for an alliance must first meet an invisible bar.
“We plan to do more deals, and we plan to do internal work in ADCs,” Sabry said in an interview with Fierce Biotech on the sidelines of the 2024 annual J.P. Morgan Healthcare Conference.
Sabry’s comments—and a recent licensing deal—marked a change of public tone at Roche toward ADCs. Back in mid-2022, chairman and then-CEO Severin Schwan told reporters that Roche had “rather limited interest” in ADCs despite other companies’ growing investments in the field.
Still, getting on Roche’s good side won’t be an easy task for prospective ADC partners—Sabry’s team reviews around 6,000 opportunities across all disease areas each year.
“For Roche, what the biotech companies are competing with is our internal work,” he said. But that internal work isn’t necessarily visible to outsiders. When asked what internal capabilities Roche has built around ADCs, Sabry said, “You’ll see when the products come.”
Roche currently has two commercial ADCs, both built with other companies’ technologies. HER2-targeted Kadcyla was made with ImmunoGen’s platform, and large B-cell lymphoma drug Polivy has Seagen to thank. But since forming those partnerships over a decade ago, the Swiss company had stayed quiet on the ADC deal-making scene, while the likes of Merck & Co., AstraZeneca, Eli Lilly and AbbVie recently bought into the field.
“We’re not a fashion company,” Sabry said. “We don’t just jump on a bandwagon because everyone else is doing it. We do things because we really believe that an innovative product will bring unusual value to patients.”
Roche broke the silence at the beginning of 2024 by in-licensing a c-MET ADC from China’s MediLink Therapeutics. The deal came more than two years since AstraZeneca and Daiichi Sankyo’s Enhertu trounced Kadcyla in a head-to-head breast cancer trial.
“Enhertu broke every rule that we thought about ADCs,” Sabry said. Roche once thought certain rules were true around the target’s overexpression level on cancer tissue, the drug-to-antibody ratio, and the stability of the linker. In the wake of the head-to-head fail against AstraZeneca's drug, Roche went back to the drawing board to renew its understanding of the modality.
“There’s a lot of internal research we were doing in order to support deals like the MediLink deal,” Sabry said.
It doesn’t mean Roche has fully understood the new rules of ADCs, Sabry said. “When you don’t know the rules, then you look for clinical data.”
“The nice thing about ADCs is that you know clinically usually within phase 1 whether the drug is safe, and whether it has some effect,” he said. “So that’s what we’re looking for. It can be very early-stage clinical data.”
Cautious approach to platform deals
As to whether Roche would buy out an ADC specialist similar to Pfizer’s acquisition of Seagen, AbbVie’s proposed purchase of ImmunoGen and Johnson & Johnson’s Ambrx takeover, Sabry said only when the external technology is “so different that we don’t have it on the inside” will Roche make platform deals. And even with platforms, Roche would typically form collaborations to generate multiple products.
Case in point: Last week Roche put down $66 million upfront to access Moma Therapeutics’ platform to identify and develop “a certain number of” novel drug targets involved in cancer cell growth and survival. In a separate deal, Roche tapped Remix Therapeutics’ drug discovery engine to develop small molecules that target RNA processing.
In the few cases where Roche has bought a company outright in the past, such as Genentech and Spark Therapeutics, the business would often be kept as a separate unit, Sabry observed.
But Roche’s $4.3 billion takeover of Spark in 2019 hasn’t produced many results, leading to 740 million Swiss francs ($870 million) worth of impairment charges for 2022.
“When we did the Spark deal, it was based on an enthusiasm around gene therapy,” Sabry said. “As you can imagine, that enthusiasm is still there, we still believe gene therapy will become a major type of therapy in the future. What we mean is that it’s going to take time for that to evolve.”
In October, Roche penned a deal potentially worth $216 million with SpliceBio for a gene therapy against an inherited retinal disease, which is Spark’s sweet spot thanks to FDA-approved Luxturna.
The gene therapy world just celebrated a major breakthrough with the approval of Vertex and CRISPR Therapeutics’ Casgevy, the first gene-editing therapy based on CRISPR technology. Still, Sabry argued that the main limitation for gene therapy is the lack of ability to target specific cells effectively.
“We would consider CRISPR, like, eventually,” Sabry said.
How the MediLink, Moma and Remix announcements appeared in close succession raises the question of whether Roche has shifted into deal-making mode. But Sabry assured Fierce that “that was just the way they lined up.” The number of deals Roche negotiated last year, including the flurry of pacts announced in the last few days, was similar to the number in previous years, he said.
Roche did appear to have spent more on later-stage candidates in 2023, including purchasing Roivant and Pfizer’s Televant for over $7 billion to get its hands on a phase 3-ready anti-TL1A antibody in bowel disease. Roche also splashed $310 million upfront to in-license Alnylam’s RNA interference hypertension candidate zilebesiran, which in September reported positive blood pressure data from a phase 2 trial.
A few trial failures have left some room in Roche’s late-stage pipeline and created an urgency to fill it, Sabry acknowledged. Besides, the biotech winter also opened projects up for the Swiss conglomerate to grab.
But Roche didn’t start the year by setting a quota to balance drug discovery pacts and late-stage buys, Sabry said. The decisions are based on science.
“We believe that the most interesting companies are the ones that dramatically change the way we think about what a medicine is,” Sabry said. He noted how Alnylam’s zilebesiran is the first to go further upstream of a signaling cascade than other existing hypertension meds.
Roche’s pharma division currently doesn’t have any commercial presence in cardiovascular or metabolic diseases—although that looks set to change. When asked if the Alnylam deal indicates a new push into that area, Sabry said: “Yes, absolutely, we’re gonna be evolving into new medicines in metabolic disease [and] in cardiovascular disease, for sure.”
All eyes on China
Another thing that Roche seems to be doing differently is that it’s recently started to partner with biotechs from China. In addition to MediLink, Roche’s Genentech paid $60 million upfront in August 2022 and committed $590 million in biobucks to in-license an androgen receptor degrader from Jemincare. By May 2023, the Swiss drugmaker was laying out $70 million in upfront and near-term payments to obtain a brain-penetrating HER2 molecule from Zion Pharma.
Sabry called those candidates “world-class drugs” that can compete with others from Western companies. Roche has also set up a business development team based in Shanghai led by Harm-Jan Borgeld, head of Asia partnering.
China has become a hotbed for partnering, especially in ADCs. MediLink has also out-licensed its ADC candidate to BioNTech, for example, while Hansoh holds two ADC deals with GSK. Merck also has a multi-program ADC collab with Kelun Biotech, and in December Bristol Myers Squibb shelled out $800 million upfront in a deal worth up to $8.4 billion for an EGFRxHER3 bispecific ADC from SystImmune, a subsidiary of China’s Biokin Pharmaceutical.
“I believe China will become as powerful as America and Europe in terms of invention,” Sabry said.
The biotech winter was also one of reasons behind the torrent of deals in China as local firms partner up to survive. “China has not matured fully into the late stages of development yet, but it will,” Sabry predicted.
“The issue in China is that they don’t have mature management teams for these biotech companies, because they are still a young industry,” he said. Once Chinese biotechs and their management develop, they will find other resources to take them forward because “the capital flows where the innovation is,” Sabry observed.
As for the potential risk of heightened geopolitical tensions, Sabry said: “When we go to China, we hope that the Chinese look at us and [think of us as] a Swiss company, not an American company.”