JPM25: Incyte plans to turn 'a lot of cards' in 2025 as CEO eyes 2 types of deals

During his presentation at the J.P. Morgan Healthcare Conference last week, Incyte CEO Hervé Hoppenot took investors on a whirlwind tour of 18 events that could take place throughout 2025.

“We will be turning a lot of these cards during the year,” Hoppenot said during an interview with Fierce Pharma on the sidelines of JPM.

Among the 18 events, Incyte is preparing for four launches across cancer and immunology, and it’s gearing up for four pivotal readouts, including two that investors are watching closely. Overall, Hoppenot said he’s looking forward to an eventful 2025 as Incyte reels from some bad news in its pipeline and as the company remains open to two specific types of deals.
 

Expanding commercial products
 

Together with partner Syndax Pharmaceuticals, Incyte in August won the FDA’s approval for Niktimvo in third-line chronic graft-versus-host disease. Trying to get a smaller vial approved, the partners are aiming to embark on an official rollout soon.

Also in immunology, Incyte is trying to build on the successful launch of Opzelura cream, with a proposed pediatric expansion in atopic dermatitis submitted to the FDA and a phase 3 prurigo nodularis readout expected in the first half of 2025.

On the oncology side of the business, the firm is counting on two potential FDA nods in the second half of the year—one for CD19 antibody Monjuvi in follicular lymphoma and the other for PD-1 inhibitor Zynyz in first line squamous cell anal carcinoma.

Incyte had originally tried to get Zynyz approved in previously treated anal cancer, but its effort was shot down by the FDA in 2021 after a negative review from an advisory committee.

This time, Hoppenot argued Zynyz’s data set in the first-line setting is “as clear as it could be,” adding that the company doesn’t anticipate any regulatory hurdles. In a first-in-class win, Zynyz and chemotherapy slashed the risk of progression or death by 37% compared with chemo alone in first-line anal cancer in the phase 3 POD1UM-303 trial.

Incyte last year also reported a positive outcome from the POD1UM-304 study, which pitted a Zynyz-chemo combo against solo chemo in first-line non-small cell lung cancer. Given the chemo comparator arm and how PD-1 drugs such as Merck & Co.’s Keytruda have already become the standard of care, the FDA will probably not consider Incyte’s study sufficient to support an approval.

Incyte is still speaking with the FDA about the indication, and Hoppenot acknowledged that the agency has “been always asking questions about the relevance of having one more of the same thing.”

But the company’s main business plan for the PD-1 latecomer is not necessarily in the U.S. market. Instead of the drug becoming a big contributor to the top line, Hoppenot views Zynyz as an “opportunistic product” for parts of the world where first-line access to PD-1 drugs isn’t established. 

To seek easy green lights in places such as the Middle East and Brazil, Incyte will first need a reference approval. If not from the FDA, such a nod could come from authorities in the U.K. or Switzerland, Hoppenot explained. This strategy of using a reference approval to move into emerging markets is also being used by many Chinese PD-1 developers.

The biggest opportunity that could emerge from Incyte’s oncology department in 2025 is an upcoming phase 3 readout for Monjuvi in first-line diffuse large B-cell lymphoma (DLBCL). While this is a large indication, Incyte is forecasting a U.S. market opportunity below $1 billion, partly because of competition from Roche’s recent entrant, the antibody-drug conjugate Polivy.

After Roche’s hard-fought first-line approval for the Polivy-R-CHP combination regimen in 2023, around 20% of new DLBCL patients are starting on the regimen, Hoppenot noted.

Meanwhile, Incyte’s phase 3 frontMIND study is testing the addition of Monjuvi to the R-CHOP regimen versus R-CHOP itself. Hoppenot said he’s optimistic about a positive readout given the strong performance of the CD19-CD20 combination approach in follicular lymphoma in the phase 3 inMIND trial.
 

Advancing a ‘full’ portfolio despite setbacks
 

In keeping with the cards theme, Incyte has faced its share of difficult poker hands lately. And the CEO continues to field investor questions about life after Jakafi’s expected loss of exclusivity in the U.S. in 2028.

The most disappointing development the company has faced is perhaps a preclinical toxicology discovery from INCB000262, the crown jewel of Incyte’s $750 million buyout of Escient Pharmaceuticals. As a result of the safety signal, clinical development of the MRGPRX2 inhibitor was put on hold in November, less than six months after the acquisition.

While Incyte is still trying to elucidate the problem and has not decided whether it needs to turn to a backup molecule, “the probability of moving forward is relatively low,” Hoppenot explained.

“You can acquire an asset that is well understood and that will cost you billions, or you acquire an early asset, like what we did, and it will cost you millions instead," Hoppenot said. 

“There is no way you can predict it, and that’s part of the trade-off,” the CEO added.

Another safety cloud forming over Incyte’s pipeline pertains to the BET inhibitor class. Novartis recently postponed potential regulatory filings for its BET inhibitor candidate pelabresib, which was acquired in its $2.9 billion MorphoSys takeout, because of malignant transformations identified during clinical testing.

Updated MANIFEST-2 trial data presented in December showed that among myelofibrosis patients who received the combination of Jakafi and pelabresib, 6.1% developed acute myeloid leukemia (AML). The number compared with 4.2% for those who took Jakafi alone.

In a phase 1 study, Incyte spotted a rate of AML transformations of 4.9% for its BET inhibitor INCB057643 among patients with high-risk myelodysplastic syndromes or myelofibrosis.

Patients with those blood disorders are naturally at risk of developing AML, Hoppenot noted, arguing that it’s too early to conclude there is a classwide problem for BET inhibitors. The only way to know for sure is through a randomized study with a comparator arm.

Unlike Novartis’ front-line study, Incyte is launching a phase 3 trial for its BET inhibitor as a monotherapy in the post-Jakafi setting. The company has not decided whether it will run a similar BET-Jakafi combo trial in the first line “because there is a portfolio question for us with two other projects,” Hoppenot said, pointing to the company's early-stage mutant CALR antibody and JAK2V617F inhibitor.

Depending on phase 1 readouts for those candidates, Incyte will have the luxury of deciding whether it makes sense to move a BET inhibitor into the first-line setting, the CEO explained.


An opportunity in hidradenitis suppurativa 
 

Despite questions around the BET class and the Escient buy, Hoppenot argued Incyte’s portfolio is currently “full.” Investors are also waiting with bated breadth to see phase 3 results for povorcitinib in hidradenitis suppurativa (HS) in the first quarter of 2025.

HS represents a historically underserved population. For years, AbbVie’s Humira served as the only treatment option until the recent approvals of Novartis’ Cosentyx and UCB’s Bimzelx, Leerink Partners analysts said in a recent note.

Studies suggest the disease affects about 4% of the population, according to Leerink. If successful, Incyte's povorcitinib could become the first oral drug for the indication. 

HS could represent a $10 billion annual market opportunity that's “capable of supporting multiple blockbuster agents,” according to the Leerink analysts. 

“We know in dermatology, there are a lot of patients who would rather be treated with the pills than with an injection,” Hoppenot noted, pointing to how Amgen’s Otezla has been successful in psoriasis even though it’s considered less efficacious than biologics.

What Incyte is gunning for is biologiclike efficacy in an oral drug, Hoppenot said of povorcitinib.

The chief executive didn’t directly answer a question about whether Incyte would need to turn to M&A if povorcitinib were to fail in HS. For now, with a “full” portfolio, Incyte is only considering two types of deals, according to Hoppenot.

“If we look for something, it would be mostly new technologies that we don’t have. So, early-stage, exotic stuff,” Hoppenot said, “or on the opposite end, commercial product, because that will be contributing to the top line immediately.”

The company will also stick to its interest areas, namely cancer and dermatology, he said.