Innovent Biologics

Likely encouraged by Tyvyt's non-small cell lung cancer data, Eli Lilly recently expanded its partnership with Innovent Biologics to cover ex-China markets. (Innovent Biologics)

Innovent Biologics
CEO: De-Chao Michael Yu
Founded: 2011

Innovent Biologics is best known for its partnership with Eli Lilly on PD-1 inhibitor Tyvyt (sintilimab), which was co-invented by Innovent CEO Michael Yu and was first approved in China in December 2018 for relapsed or refractory classic Hodgkin’s lymphoma (cHL) after at least two prior lines of therapy.

Yu is the inventor of Oncorine, a genetically modified oncolytic adenovirus that was the first commercialized virus-based anti-tumor therapy.

Lilly’s venture capital spinoff Lilly Asia Ventures first invested in Innovent in 2012, a year after Yu founded the firm. Then in March 2015, Lilly itself put down $56 million upfront for Chinese rights to a “preclinical immuno-oncology molecule” and an anti-CD20 antibody by Innovent, with more than $400 million also up for grabs. It became clear later that the I-O drug was Tyvyt and the anti-CD20 was a Rituxan biosimilar, approved in China mid-2019.

Dozens of PD-1/L1 drugs are being developed in China amid a craze for I-O, all hoping to replicate or even top the clinical success of Bristol Myers Squibb’s Opdivo and Merck’s Keytruda. And the Chinese PD-1 market is nothing to sneeze at; it will contribute $13.1 billion to the global PD-1 market of $78.9 billion by 2030, according to Frost & Sullivan.

Innovent is definitely one of those touting best-in-class potential for its candidate. Its optimism is based on Tyvyt’s higher affinity to its target compared with Keytruda and Opdivo, and it appears to occupy more of the PD-1 binding sites than Opdivo.

RELATED: WCLC: Lilly, Innovent tout Tyvyt front-line lung cancer win. Can it challenge Merck’s Keytruda?

Results from Tyvyt’s first registrational trial lent credence to its case. In the phase 2 Orient-1 trial, Tyvyt triggered a response in 80.4% of 92 Chinese patients with r/r cHL after a median 10.5 months of follow-up. About 34% of the patients went into remission with no signs of cancer. The study was featured on the cover of the January 2019 issue of The Lancet Haematology.

The data look on par with Opdivo’s and Keytruda’s from their separate trials, although cross-trial comparisons have their problems. Keytruda’s overall response rate in the Keynote-087 trial was 69%, with a complete response rate of 22.4%. Combined analyses of Opdivo’s phase 2 CheckMate-205 and phase 2 CheckMate-039 trials showed a response rate of 65%.

In late 2018, Tyvyt became the fourth PD-1 approved in China—after Opdivo, Keytruda and Junshi Biosciences’ Tuoyi (toripalimab)—and the first for cHL.

Innovent makes developing and selling “high quality biopharmaceutical products that are affordable to ordinary people” as its mission. Guided by that motto—and a goal of quickly snaring market share amid increasingly heated competition—Innovent and Lilly this year cut Tyvyt’s price by 64% to become the first and only PD-1 covered by China’s National Reimbursement Drug List. In the first half of 2020, Innovent recorded Tyvyt sales of CNY 920.9 million ($137.4 million).

That willingness to lower prices could be music to the FDA’s ears, even though the agency doesn’t have authority over drug prices. At last year’s American Association for Cancer Research annual meeting, Richard Pazdur, director of the FDA’s Oncology Center of Excellence, welcomed China-made PD-1/L1 inhibitors to apply for U.S. approvals to bring down prices currently set by Western pharmas. He also said the agency would consider submissions based solely on Chinese data if they are of good quality.

RELATED: China gives Merck, BMS cold shoulder on reimbursement list as PD-1 battle enters new phase

One major commercial advantage of PD-1/L1 antibodies is that they are expected to reach multiple cancer types, including some of the most prevalent cancers in China. Lilly and Innovent already have positive results in non-small cell lung cancer, which, as is the case in the U.S., represents the largest cancer group in China.  

For previously untreated nonsquamous NSCLC, adding Tyvyt to Lilly’s Alimta and platinum chemo cut the risk of disease progression or death by 52%. Patients on the Tyvyt regimen lived a median 8.9 months without disease worsening, compared with 5 months for the chemo group, according to data from the Orient-11 trial.

Those numbers are very similar to what Keytruda posted in its Keynote-189 study, in which the addition of the Merck drug to chemo slashed the risk of disease progression by 51%; as progression-free survival measured 8.8 months for the Keytruda group, versus 4.9 months for the chemo control group.

Success was also achieved in first-line squamous NSCLC. A combination of Tyvyt, Gemzar and platinum chemo reduced the risk of cancer progression or death by 46% over chemo alone in the Orient-12 trial.

Life-extension data for Orient-11 and Orient-12 have not matured so far, but investigators observed benefits for the Tyvyt combo in both trials. Eventually, Keytruda’s 50% death risk reduction in Keynote-189 will be Tyvyt’s target to beat. Applications for those two indications have already been accepted for review by Chinese authorities.

RELATED: With 6 rivals in the U.S., why would Lilly shell out up to $1B for Innovent's PD-1 med Tyvyt?

Lilly was obviously encouraged by those results. The Indianapolis pharma in August expanded its licensing deal with Innovent to also include ex-China markets in a deal potentially worth over $1 billion.

The two companies are deeply connected. Besides Tyvyt, they're collaborating on up to three bispecific antibodies based on the PD-1 through a deal they signed in October 2015. Last August, Innovent in-licensed Lilly’s OXM3, a dual GLP-1 and GCGR agonist, whose China phase 1b/2 just kicked off in September.

At the end of the day, Innovent doesn’t want to be a one-trick pony, having established a pipeline of over 20 clinical-stage candidates spanning cancer, metabolic, ophthalmology and autoimmune diseases.  In June, it tapped Roche’s technologies in T-cell bispecific antibodies and CAR-T to help design bispecifics and cell therapies.

Innovent Biologics