Innovent Biologics Inc., of Suzhou, has out-licensed ex-China rights for its PD-1 drug Tyvyt (sintilimab) to Eli Lilly and Co. in an expanded license deal. The Chinese firm will receive $200 million up front in the deal, the value of which could approach up to $1.03 billion.

Innovent’s CEO Michael Yu called this “the first solid step in getting Innovent's innovative portfolio into the global market.” With the ex-China rights of Tyvyt, Lilly plans to seek approval for the PD-1 drug in the U.S. and other markets. The Chinese firm will be eligible for up to $825 million in development and commercial milestones, plus tiered double-digit royalties on net sales. Both companies also have the right to study Tyvyt in combination with other agents from their own pipeline.

The Aug. 18 deal was an expansion of a $456 million pact entered with Lilly in 2015, under which both companies agreed to jointly develop and commercialize Tyvyt in China. Innovent’s CFO Ronnie Ede described the $1.025 billion expanded deal as “historic.”

“This is the largest [deal] for a late-stage PD-1 asset to be licensed to a multinational company,” Ede told BioWorld. “This is the only [PD-1 inhibitor] actually finding a global partner to take it on the global basis.”

Though Lilly has yet to reveal any commercialization plans for Tyvyt, Ede said the company is definitely looking at the U.S., the EU, and Japanese markets. “With Lilly, we will take the lead, and we will supply and assist in any way we can,” he added.

In 2018, Tyvyt was approved in China for relapsed/refractory classical Hodgkin lymphoma. The drug generated ¥900 million (US$130 million) in sales during the first half of 2020, turning Innovent from a pre-revenue startup into a profitable company.

So far only approved in China, it’s one of the first NMPA-cleared PD-1 drugs and the only one included in China's national reimbursement drug list, which means it can be made available in all state-run hospital pharmacies.

Innovent has been collaborating with Lilly since 2015. After the alliance on Tyvyt and other cancer treatments, both companies in the same year entered another agreement worth $1 billion to co-develop three bispecific antibodies. In 2019, they signed another deal to develop and commercialize diabetes drug OXM-3, a dual GLP-1 and glucagon receptor agonist, in China.

When asked how the $200 million up-front payment will help Innovent further advance its R&D, Ede told BioWorld that “money is good, but we do have enough cash,” adding that the now-profitable company has $1.2 billion in cash reserves.

“The price [Lilly] is paying is more a reflection of the value of the deal, but not really the money we urgently need for [R&D],” he added.

PD-1 inhibitors are largely seen as promising cancer drugs and backbones for many combination therapies. To maximize Tyvyt’s clinical value, Innovent is conducting more than 20 clinical studies to explore its potential for treating different cancer types, such as lung, esophageal and rare cancers. Again, Innovent is collaborating with Lilly in some of the studies.

One of these studies evaluates Tyvyt in combination with Lilly’s chemotherapy drug Alimta (pemetrexed disodium) and platinum chemotherapy as a first-line therapy for advanced or recurrent non-squamous non-small-cell lung cancer (NSCLC) without sensitizing EGFR mutations or ALK rearrangements.

Interim analysis data from the phase III trial showed that the combination therapy demonstrated a statistically significant improvement in progression-free survival (PFS). Innovent is seeking a supplemental NDA for this indication in China, and both companies plan to pursue NDAs in the U.S. and other markets.

In another phase III study, Tyvyt was combined with Lilly’s chemotherapy drug Gemzar (gemcitabine) and platinum chemotherapy as a first-line therapy in patients with locally advanced or metastatic squamous NSCLC. The study met the predefined primary endpoint by demonstrating a statistically significant improvement in PFS, and a supplemental NDA has also been filed in China.

As a monotherapy, Tyvyt met the primary endpoint of overall survival as second-line therapy in patients with advanced or metastatic esophageal squamous cell carcinoma in a phase II trial.

This year, Innovent will also start working with The University of Texas MD Anderson Cancer Center to co-develop Tyvyt in rare cancers in the U.S.

Aside from Tyvyt, Innovent has other candidates, such as an anti-CD-47 candidate IBI-188, which is in phase I trials, a bevacizumab biosimilar IBI-305 out-licensed to Coherus Biosciences Inc., a PD-1/CD47 bispecific antibody IBI-322 in phase I trials, and an anti-TIGIT antibody IBI-939. To date, it has 23 late- and early-stage assets in its pipeline.

“We have several assets with worldwide rights. We are looking into gradually establishing our presence in different parts of the world,” said Ede, when asked about the company’s future plans to consolidate its global footprint. “We have to learn how to walk before we can run.”

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