As Bristol-Myers merger marches ahead, what's BeiGene's plan for Celgene-partnered PD-1?

BeiGene expects Celgene returning the PD-1 rights after Bristol-Myers merger will have "marginal" impact, says a Beigene executive. (Pixabay)

Now that the $74 billion acquisition of Celgene by Bristol-Myers Squibb is more or less a done deal, one question remains for BeiGene: What does it plan to do with its Celgene-partnered checkpoint inhibitor, tislelizumab?

The short answer? If—or, most likely, when—BeiGene does end up flying solo with the PD-1 immunotherapy, the impact on clinical development would be “marginal,” and the financial hit would be “modest,” BeiGene Chief Adviser Eric Hedrick, M.D., told FiercePharma in an interview.

The concern isn’t so much about BeiGene’s path forward for tislelizumab in China, where it’s under priority review for classical Hodgkin lymphoma (cHL), but rather in the U.S., EU and Japan in solid tumors. Those are the areas where Celgene currently holds tiselelizumab rights.

“In the contract, there’s stipulation that they basically can’t hold two PD-1-class assets,” Hedrick said of BeiGene's pact with Celgene. That means, once the merger closes as expected in the third quarter, there’s no reason for Opdivo seller BMS to hang onto tislelizumab. “We fully expect that the rights to our PD-1 inhibitor globally will be transferred back to us,” he said.

BeiGene made its name back in the summer of 2017 when it penned that unusual deal with Celgene. Under the agreement, Celgene made a $150 million investment in BeiGene and transferred its Chinese commercial operations, including rights to marketed drugs like Revlimid, to the Chinese biotech.

The BMS-Celgene merger will have “zero” effect on that part of the deal, Hedrick said. And the second part saw Celgene shell out $263 million upfront for tislelizumab rights.

At the time, BeiGene was just a small company. “One of the appealing aspects of doing this deal was for us to bolster our capability to develop that drug on a global basis,” Hedrick explained.

That has changed dramatically over the past two years, he said, and BeiGene’s in a good position now to run the show. Its ability to conduct clinical development globally has “increased exponentially,” he added.

Today, BeiGene's clinical development team is more than 800 strong, with about half of those employees located outside of China. And that team is handling more than 50 ongoing or planned clinical studies as of January, the company said in its recent annual securities filing.

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For tislelizumab specifically, 90% of the registrational trials are already in BeiGene's hands, so “the operational impact for us is negligible,” Hedrick said, adding that the company doesn’t expect any major hiring or organizational changes. The only major study conducted by Celgene is testing tislelizumab alongside chemo and radiation as a post-surgery treatment for locally advanced non-small cell lung cancer.

“The financial aspects of us getting rights back would be mitigated by the fact that all the trials that we’re getting reimbursed by Celgene will complete accrual by the end of the year,” he said.

That said, development is only part of the picture, and merely pushing the drug to approval doesn't necessarily translate into commercial success. Without help from an oncology bigwig, marketing neophyte BeiGene might have a tough time launching, especially in the U.S. where Merck & Co.’s Keytruda, BMS’ Opdivo and Roche’s Tecentriq have secured footholds in many major indications.

BeiGene could take a page from Sanofi and Regeneron, though. The pair first went after a small niche market with their sixth-to-market Libatyo.

“If you look at the first wave of registrational trials, a lot of those are in the cancer types that are prevalent in Asia,” Hedrick said. Lung cancer is of course part of that cohort, as it’s the most common cancer type in China as well as in the U.S. But many studies are in gastrointestinal-related malignancies, such as liver, stomach and esophageal cancers, that are also common on the continent.

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“The China part of that commercialization is going to be a major focus,” Hedrick said. “That’s how we think we can be competitive.”

By focusing on Asia-prevalent cancers, BeiGene could stake a claim in Asia and other parts of the world. Just consider gastric cancer, where Keytruda has failed phase 3 studies in both newly diagnosed and previously treated patients.

For now, BeiGene is building its global commercialization presence “step-wise,” Hedrick said. It has brought in a senior team to handle U.S. sales and marketing for its BTK inhibitor zanubrutinib, for instance, which recently became the first China-developed drug to win an FDA breakthrough designation.

The first U.S. filing for that drug, in Waldenström's macroglobulinemia, will happen in the first half of next year, and it will be another year before it’s tislelizumab’s turn, according to Hedrick.

While in the long term BeiGene aims to be a global commercialization force in its own right, in the near term for tislelizumab, it might scout for new partners if the BMS-Celgene transaction goes through as planned, Hedrick said.

The Chinese approval is more imminent: It's expected later this year. Five PD-1s are already approved in China, including Keytruda, Opdivo and three local rivals. Jiangsu Hengrui Medicine’s camrelizumab just won a nod in Hodgkin lymphoma—the same initial indication tislelizumab is after. For China, BeiGene’s plan is to run a broad development program and get “as many approved indications as possible listed for national reimbursement,” he said.

Compared to what Merck executives has touted as Keytruda’s “wall of data,” the data tislelizumab has yielded so far are quite thin. They’re mostly phase 2 results in small trial groups and only comprise overall response stats.

But BeiGene plans to build a wall of data of its own, and it has a good start. In its single-arm China phase 2 trial in 70 patients with relapsed/refractory cHL, tislelizumab achieved a complete response rate of 61%, about two times that of other PD-1 inhibitors, Hedrick touted.