For Chinese biotechs, the out-licensing business is scorching hot. Could geopolitics rain on their parade?

Athena Countouriotis, M.D., is no procrastinator—the CEO of Avenzo Therapeutics planned her March trip to China roughly six months ago. 

The goal was to sit down with the CEO of Allorion Therapeutics, a company that’s since been announced as Avenzo’s first asset partner. Allorion received $40 million upfront with more than $1 billion in biobucks on the table in exchange for the CDK2 inhibitor AVZO-021 and a preclinical program. 

Over five days in Shanghai, Countouriotis and her team met with Allorion plus new investors and other potential business partners. 

“We're very happy that we found a partner in Allorion, who truly understood our capabilities and knew that we needed to move quickly because there is competition in the CDK2 space ahead of us in Pfizer,” she told Fierce Biotech in an interview days after returning from her trip. “So we want to catch up.” 

Tapping into China’s reservoir of medicines is not a new strategy for Countouriotis—she followed a similar strategy as the CEO of Turning Point Therapeutics, which Bristol Myers Squibb ultimately bought for $4.1 billion in 2022. Now, others are catching on.

Last year was the first time that the number of out-licensing deals in China exceeded in-licensing deals, indicative of a burgeoning innovative biotech scene that’s attracting cross-region interest. Chinese biotechs executed 63 cross-region out-licensing deals in 2023, a record for the industry and an 80% increase compared to 2022, according to data from China-based life science advisory firm YAFO Life Sciences. In-licensing deals fell by 56% over the same period, from 59 to 26, the data show.

As out-licensing deals have increased, so have the financial stakes. Total upfront payments to Chinese biotechs from out-licensing deals eclipsed $2.2 billion in 2023, more than doubling on 2022. For comparison, back in 2019, Chinese biotechs collectively brought in $10 million in upfront payments from out-licensing deals. 

Leon Tang, Ph.D., a U.S.-based business development consultant who previously worked as a senior director of business development at biopharma company Henlius, says Chinese scientists have wielded their chemistry prowess to capitalize on a wave of interest in antibody advancements, including antibody-drug conjugates (ADCs). 

“[Chinese biotechs are] really leveraging their strengths in chemistry and the material sciences and world-class contract research and development organizations such as WuXi Biologics and WuXi Apptec,” he said. 

Therein lies a growing problem: The success of both companies has caught the attention of U.S. lawmakers, who mention each by name in new legislation meant to stem China’s influence on the U.S. biotechnology sector. U.S. intelligence officials reportedly briefed lawmakers that WuXi AppTec was passing along US partners' intellectual property data to the Chinese government, an allegation the company refutes. 

Interviews with company executives, investors and consultants who have experience working on cross-region deals said it remains to be seen whether the legislation could have a meaningful chilling effect on future business development tied to China, particularly in the near term. But it’s certainly thrown a wrench into what’s been considerable momentum. 

An international lawyer familiar with global business development transactions told Fierce that the BIOSECURE Act currently being considered in the U.S. House of Representatives has become an “elephant in the room” between potential partners. The source was granted anonymity to speak freely about the nature of negotiations without risking client relationships. 

“There's a lot of hand-wringing, [and] there's a lot of concern,” the source said. “I feel like the companies are not used to dealing with this type of risk.” 

While they have yet to notice a drop-off in deals as a result of the increased national security scrutiny, the source said it has stirred up preexisting questions about the integrity of data coming out of China.

Countouriotis also acknowledged that data integrity could be a limitation for biotechs planning a deal in China, but that if due diligence is successfully conducted ahead of time, companies should proceed.

“If you have full confidence in the data set, if you've repeated any of the scan reviews, and you've had a thorough freedom-to-operate analysis done, [then deals] shouldn't be treated any differently,” she said. 

China’s biotech regression

The timing of the BIOSECURE Act has added insult to injury for a Chinese biotech market that faced a difficult downturn in 2023. A report from McKinsey last year assessing the performance of 60 China-headquartered biotechs found that three out of four were trading below their IPO price as of September 2023, and $80 billion in market cap had been wiped out since a peak in June 2021. 

The private market was even bleaker, with less than $2 billion in private equity or venture capital money flowing into China's biotechs, the lowest since 2017. It was part of a larger industry downturn that battered global drug developers, both private and public. 

Ironically, the downturn struck China just as homegrown companies were beginning to reap the reward of investments from years past. Three China-based companies nabbed FDA approval in 2023, more than doubling the number of total approvals entering the year; and two China-originating drugs secured FDA breakthrough tags.

Simone Song, head of Hong Kong-based ORI Capital, described China as being in the middle of its third chapter, reaping the benefits of biotech infrastructure investments. She lamented the possibility of geopolitics stymying further collaboration with the U.S. 

“I hope that the politics do not get in the way, because the advantages of both sides are so obvious,” she said in an interview. 

Improved discovery efforts were also reflected in YAFO’s 2023 data, which showed that 41% of out-licensing deals involved preclinical assets, compared to 26% in 2022. Only 9% of out-licensed drugs in 2023 were registrational-stage, compared to 21% in 2022. Still, as expected, the most lucrative deals last year involved late-stage assets. 

Systimmune led the way, selling off rights to a phase 3-stage EGFRxHER3 bispecific ADC for $800 million upfront to BMS, the largest initial sum from any China-originating out-licensing deal in 2023. The second and third largest upfront payments totaled $750 million, according to YAFO data, which included LianBio returning greater China licensing rights back to BMS for heart failure drug, mavacamten.

New companies are looking to take advantage of the earlier-stage innovation, however. They include OnCusp Therapeutics, which is led by co-founder and CEO Bing Yuan, Ph.D. He previously served as the chief business and strategy officer at CStone Pharmaceuticals, one of the original pioneers of the in-licensing business model.

At OnCusp, Yuan is looking to tap into the exciting science originating in China by licensing assets at a late preclinical or early clinical stage, developing them in the U.S. and then adding a partner once they’ve matured. The idea is to capitalize on China’s still-improving clinical development ecosystem and get hold of assets that may otherwise languish without getting proper human data. 

“We do the early clinical development, especially proof of concept, primarily in the United States, then the data quality has no doubt,” he said. Yuan added that because Chinese biotechs have a knack for speed, OnCusp can identify assets earlier and advance them through trials so they can be first to market. He noted that scouring for preclinical assets also means you’re beating Big Pharma to the punch on possible value. 

The "China discount"

Yuan hopes OnCusp’s strategy can shed what he describes as the “China discount,” a knockdown on an asset’s price if it’s solely based on Chinese data. 

“You'll need some time to close the gap,” he said. “That's why we want to develop the data in the United States, especially patient data.”  

YAFO’s report showed that despite the total amount of upfront revenue doubling for assets out-licensed out of China in 2023, the average upfront payment rose just $5 million, from $30.7 million to $35.2 million. In 2020, the average upfront payment was less than $19 million. 

The lawyer familiar with the negotiations of related deals suggested the so-called “China discount” could be due in part to the “transactional administrative burden” that companies take on to make sure they’re following regulatory and legal guidelines, particularly on exporting Chinese patient data. But the source added that the market opportunity, or lack thereof, is likely the main contributor. 

Business development consultant Tang suggested China’s me-too reputation as another potential cause, pointing out the multibillion-dollar upfront payment that Japan-based Daiichi Sankyo struck with Merck & Co. as evidence that the Chinese market is a bit saturated. No sooner did Merck ink the Daiichi deal than it trimmed a few preclinical assets from a previous partnership with China-based Kelun Biotech. 

Compared to the $4 billion upfront that Daiichi received, Kelun had only been awarded $175 million with more than $9 billion in biobucks available. 

“I always advise my clients: If you could, try to differentiate,” Tang said.