BMO most bullish on Merck’s, bearish on BMS’ plans to contend with patent cliffs

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BMO Capital Markets is more impressed by Merck’s plans to replace lost Keytruda revenue than on Bristol Myers Squibb’s efforts to fill the expected void that will come from loss of exclusivity for both Opdivo and Eliquis.

Almost all big pharmas are contending with patent cliffs right now, putting pressure on pipeline programs and next-gen plans. While Merck and Bristol Myers Squibb both face some of the greatest exposure—for PD-1 blockbusters Keytruda and Opdivo, respectively—BMO Capital Markets believes Merck has done a better job putting sufficiently large, derisked growth products in place before erosion begins.

Of the pharma companies BMO covers, the firm is most bullish on Merck right now. Merck faces the largest single-product replacement challenge with Keytruda. The New Jersey pharma faces loss of exclusivity for its blockbuster immunotherapy beginning at the end of 2028, putting $33 billion in revenue at risk, according to a Sept. 9 report from BMO.

That being said, the first half of 2026 was a continuation of “sentiment reversal for Merck,” the analysts wrote. As of Sept. 9, Merck’s shares had risen 43% since the beginning of the year, making the company the largest gainer in BMO’s large pharma coverage.

Merck’s Keytruda may be the most talked about drug facing loss of exclusivity but it’s far from the only one, as several of the industry’s top-performers are losing key market protections. Some companies are more prepared than others.

Some of Merck’s strongest growth products include the Moderna-partnered mRNA cancer vaccine intismeran autogene, the high blood pressure medicine Winrevair and the TROP2 antibody drug conjugate sac-TMT, Evan Seigerman, BMO managing director, head of healthcare research and senior biopharma analyst, told BioSpace.

The recent success of intismeran autogene demonstrates additional opportunity for oncology expansion, Seigerman said. Meanwhile, Winrevair has shown continued commercial strength, with BMO modeling $9.1 billion in peak sales.

Then there’s the late-stage sac-TMT, discovered by China’s Kelun-Biotech, “which appears to be an increasingly meaningful part of the Keytruda solution,” according to BMO’s report. Recently, the asset improved progression-free survival compared to a Keytruda and chemotherapy combination in the Phase 3 OptiTROP-Lung06 trial. BMO projects peak sales of $4.3 billion for sac-TMT, which has secured breakthrough status and a Commissioner’s National Priority Voucher from the FDA.

Seigerman also highlighted Merck’s anti-TL1A antibody tulisokibart, gained in the company’s $10.8 billion Prometheus Biosciences buy in 2023. Just this week, Merck shared data behind a mid-stage win in hidradenitis suppurativa that the analysts say could help carve out a place in a crowded market that already includes AbbVie’s Humira and UCB’s Bimzelx.

“They actually probably have a credible foray into I&I [immunology and inflammation],” Seigerman said. “Beyond that, they’re still always the leader in oncology, whether it’s their TROP2, what they’re doing in PD-L1/VEGF or their collaboration with Moderna on a personalized cancer vaccine. So, they’re pretty solid there.”

On the flip side, Seigerman said, BMS has done a less-stellar job at preparing for Opdivo’s loss of exclusivity, which will also hit starting in 2028.

“It’s a smaller revenue base, but it’s still $16-plus billion, and I think that they’ve done not as good of a job as solving for that,” he said.

Alongside Opdivo, the New Jersey–based pharma must contend with the 2028 patent loss of its other top-selling drug—Pfizer-partnered blood thinner Eliquis—creating “the greatest combined exposure,” according to BMO’s report.

Last year, Eliquis brought in $14.4 billion in global sales, while Opdivo secured $10 billion in worldwide revenue—together accounting for roughly half of BMS’ entire $48.2 billion revenue. The size of Eliquis and Opdivo “means BMS still requires substantial growth from its newer products to stabilize revenue later in the decade,” BMO wrote.

While both drugmakers face looming patent cliffs, analysts say joining forces could help Bristol Myers Squibb replenish its eroding portfolio—while the strategic case for AstraZeneca seems to be more mixed.

In addition, the assets BMS has set up as potential revenue replacements are much riskier than Merck’s, according to Seigerman.

“Cobenfy, their schizophrenia drug, is not selling that well,” he explained. Cobenfy brought in $155 million in sales for BMS in 2025, well below some analysts’ predictions during the drug’s late-stage development at Karuna Therapeutics. BMS picked up Cobenfy—formerly KarXT—via its $14 billion acquisition of Karuna in 2023.

Despite the recent emergence of a new drug class, schizophrenia remains one of the most challenging neuropsychiatric diseases to treat—and Cobenfy’s first steps into the market indicate there is still room to grow.

BMS is expecting a Cobenfy readout in Alzheimer’s disease psychosis in early 2027—findings that were delayed after the program faced enrollment challenges—but that’s far from a sure bet, according to Seigerman.

“You have Cobenfy in Alzheimer psychosis—that’s pretty risky,” he said. “That’s a binary stock move for a big company.”

If Cobeny does prove successful in Alzheimer’s psychosis, BMO believes the drug could represent a $4.4 billion unadjusted peak revenue opportunity for the indication. BMS also has several other clinical readouts for the program that could provide greater clarity on the breadth of the opportunity, BMO noted.

Then there’s milvexian, a Johnson & Johnson–partnered investigational oral Factor XIa inhibitor. BMS has also delayed topline results for this asset in atrial fibrillation. The data delay follows the early discontinuation of a separate Phase 3 trial for milvexian late last year in acute coronary syndrome study,

“If that doesn’t work, then I feel like Bristol is going to be kind of . . . really back at the drawing board,” Seigerman said of the company’s bets on milvexian.

Then there’s admilparant, BMS’ late-stage pulmonary fibrosis candidate. Earlier this week, reports circulated about several liver injuries, including one death, among patients receiving the drug.

“The problem with Bristol is that there’s so much riding on these three assets,” Seigerman said.

BMS is barreling toward a clinical trial readout that an H.C. Wainwright analyst believes could contribute to the return of mergers between mega-cap drugmakers.

Gabrielle Masson is an award-winning biopharma editor and writer with more than seven years of journalism experience in life sciences and healthcare. Subscribe to the daily GenePool and weekly Manufacturing Brief newsletters she curates here, and contact her at gabrielle.masson@biospace.com.

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