China gets ready for immunotherapy future despite uncertainty

SUZHOU, China – At the Chinabio Partnering Forum, a panel of leading Chinese biopharma founders and executives discussed the future of immuno-oncology in China to a packed room in Suzhou, a biotech hub a short distance from Shanghai. The speakers were cautiously optimistic about China’s future in this hot new category of cancer treatment, artfully skirting around direct mention of the government’s recent ban on immunotherapy following a scandal involving a patient who died after receiving DC-CIK treatment. (SeeBioWorld Today, May 10, 2016.)

Given how fast things can change here, most have a glass-half-full perspective: that the ban will only be temporary and public pressure will force regulators to come up with a stricter policy beneficial to companies that deliver data-driven results. Although when that will happen is anybody’s guess.

“I see [the controversy] more positively, as long as companies can demonstrate the value of a treatment,” said Zhengying Zhu, deputy general manager of Luoxin Biotechnology Shanghai Co. Ltd.

Regulatory uncertainty aside, Chinese biopharmas are jockeying for position in China while many others are hoping for a lucrative out-licensing deal – especially in the area of checkpoint inhibitors. It was debated whether there might be 50 or 100 Chinese companies developing PD-1 or PD-L1 antibodies; either way, it is clear the market is crowded.

Amongst local companies, relatively little-known Junshi Biosciences Co. Ltd., of Shanghai, is the front-runner. Junshi is the first local company to gain CFDA approval to initiate clinical trials for a PD-1 candidate. (Other companies like Beigene Co. Ltd. went to Australia with their PD-1 drugs to collect clinical data and avoid the long regulatory wait times in China. But the company to beat is Bristol-Myers Squibb Co., which started its China phase III trial for Opdivo (nivolumab) in December last year.)

Jiangsu Hengrui Medicine Co. Ltd. has also started PD-1 trials and is trying to get the product to market as soon as possible, said Mike Liu, the company’s head of global business development. Hengrui has become the model for what a homegrown Chinese PD-1 can accomplish outside of China. Last year, Hengrui made a historic licensing deal, selling the rights to its PD-1 to U.S. firm Incyte Corp. for $795 million.

Liu admitted that last year was a busy one for him. “I was closing two partnerships a month: immuno-oncology on top of the PD-1.”

Given the crowded field, it might be reasonable to assume that the dozens of Chinese checkpoint inhibitors will not be ready until it is too late to make a difference. But Henry Ji, president and CEO of Sorrento Therapeutics Inc., came to the meeting prepared with encouraging words.

“Biotechs have the advantage,” said Ji. “They may think they are late to the game, but many smart companies have been working hard – with their head down and eyes closed – and now they find out the big guys actually want it. That PD-1 and PD-L1 are the cornerstone of any combination. Pharma may have a dozen combo possibilities in the pipeline, but they have to combine with the PD-1, PD-L1 – and they need to have their own.”

Ji has come up with his own formula to describe the current situation, designed to entertain the audience. “There are the SAD companies, doing ‘search and development,’ and then there are the BAD guys, they do ‘buy and development,’” Ji explained. “Now, the little guys have an advantage. They become the granddad for all these SAD and BAD guys. They are the DAD: discover and develop.”

PLAY YOUR HAND WELL

But the consensus was that it is not enough to have a solitary checkpoint inhibitor in the pipeline. Given the number of companies going after the same targets, “there will be losses, not all them good,” said Cyrus Mirsaidi, president and CEO of Bioduro LLC.

In the case of Zai Labs Ltd., its discovery efforts are immunotherapy-focused in areas such as B cells, NK cell and macrophage – but not PD-1. Samantha Du, CEO of Zai Labs, likened it to a game of mahjong (a Chinese game similar to playing cards), in that the better hand you hold, the better your chances of success.

“We would rather partner with those companies that have a PD-1 and we can trade with other partners. Playing the immuno-oncology space is like playing mahjong – you are always trying to get better cards, but if you only have one card, you have to think about what is your strategy. You can’t win in mahjong with one card,” said Du.

She added, “Right now there is no combo therapy in China. It might take another five years. China might have a better strategy and better buying power in future. We should develop combo therapies, not thinking about today.”

San Diego-based Sorrento has, in fact, been planning for quite a while on how to do combinations. Invested by Patrick Soon-Shiong of the Moonshot 2020 program and with $150 million from Ally Bridge, Sorrento also has extensive operations in China.

“What is a combination? Synergistically, it is all the little bits – the modalities – added together that can be a game-changer. Sorrento has many modalities: in killing, blocking, and then with cells for activation,” said Ji. The company’s pipeline has six monoclonal antibodies, five CAR T assets and two CAR T NK programs. It also formed a company with City of Hope called LA Cell to acquire technology designed to go where the majority of cancer targets can be found – inside the cell.

“Instead of doing a different modality, we plan to deliver the antibody to an intracellular target,” said Ji. “That is the holy grail. . . . Instead of an army at the gate [outside the cell], you can have a heat-seeking missile right on the target.” Ji is counting on that not only being more effective, but also requiring fewer antibodies to manufacture, which will reduce cost.

Affordability of immunotherapy in China was never far from the panelists’ minds. Getting the new treatment to scale commercially in China is another area where uncertainty reigns and the future is unclear.

Smart development strategies can help, such as bispecific antibodies or going for intracellular technology. Others also look to demographics, pinning their hopes on China’s aging population, the government stepping up or the growing middle class.

“China is not a homogeneous population; there are at least three layers,” said Zai Labs’ Du. “There is a group of extremely wealthy people that will fly to get treatment elsewhere if it is not available in China. This is already happening for PD-1 and other types of treatments. The second layer, the so-called middle class, they wish the government can help, but they will pay out of pocket, even it bankrupts them. Then there are those with no resources who will suffer the most when we talk about the issue affordability.”

In the end, patients drive the need, Du added, and the expectation is that the government will have to find a way to supply it.

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