Looking back, 2021 can be seen as the height of the gene therapy boom. At the time, companies worldwide were scrambling to go public, while pharmaceutical giants like Novartis, Bayer, and Eli Lilly made strategic acquisitions to carve out their share in the space. China, though still developing its domestic gene therapy ecosystem, was indirectly bolstered by the surge in innovative drug companies, especially in attracting talent.
Wu Zhenhua returned to China in 2019 to launch Exegenesis Bio, seizing the opportunity presented by the industry’s upward trajectory.
“It has been deeply rewarding,” Wu said at the 13th China Rare Disease Summit Forum in September, reflecting on his five-year entrepreneurial journey. Wu, with prior stints at Merck & Co. and GSK, built Exegenesis Bio to focus on gene therapies targeting diseases in the central nervous system, ophthalmology, and liver. The company, having raised over USD 120 million, is advancing a type 1 spinal muscular atrophy (SMA) gene therapy now in Phase 2 clinical trials in China.
As the first gene therapies reached the market, the excitement around them began to meet a reality check.
One major challenge is price—often astronomical due to the high production costs of therapies designed to treat rare diseases. Promising long-term effectiveness from just one dose, these treatments come with hefty price tags. According to 36Kr, at least eight FDA-approved gene therapies in the last seven years have crossed the USD 2 million mark per dose, with the highest soaring to USD 3.5 million. The cost ceiling for breakthrough drugs keeps climbing.
Wu believes that the period between 2019 and 2022 marked gene therapy’s first wave of commercial success, with multiple products gaining approval and some achieving impressive commercial outcomes. However, there have been setbacks—certain therapies underperformed due to safety concerns or limited efficacy in trials, while others struggled commercially.
He identifies two key hurdles: first, current gene delivery systems need better efficiency and precision targeting. Second, some treatments aren’t fully meeting patient needs. Still, Wu argues that these issues aren’t directly tied to the high costs of manufacturing or the “one treatment, long-term efficacy” pricing model. Thanks to advances in production, costs are increasingly under control, and overseas markets have embraced the high price tags for these therapies. Several successful products have validated this approach.
With the groundwork laid by earlier therapies, Wu sees the industry entering a second phase of growth, driven by improved tools and deeper understanding of the diseases gene therapy aims to treat.
A key example is the evolution of delivery vectors. The first generation relied heavily on wild-type adeno-associated virus (AAV), a simple DNA virus that efficiently infects human cells. While a breakthrough over previous retroviral vectors, AAV came with its own limitations in terms of safety and efficacy.
Now, the field is moving toward third-generation vectors that build on the capabilities of AAV, significantly improving both efficiency and safety. For muscle tissue, delivery efficiency has increased from 30–40% to over 90%. For neural cells, the jump has been even more dramatic—from 1% to 50–80%. “For diseases like Parkinson’s or Alzheimer’s, treating just 1% of cells wasn’t enough to make a difference. But if we can target 70%, the results could be transformative,” Wu said.
On the safety front, the newer vectors allow for more precise targeting. “When we delivered AAV9 to muscle cells in the past, most of it would end up in the liver, leading to toxic side effects. Now, with the new vectors, 90% of the delivery can bypass the liver altogether, making the treatment much safer,” he added.
These technological strides are also creating space for more innovative, differentiated therapies. While current SMA gene therapies have greatly improved survival and motor function, they haven’t yet enabled patients to live entirely normal lives.
“About 10% of patients can stand, but they don’t move like healthy children,” Wu said. “One treatment does provide long-term benefits, but we’re not yet seeing a full cure. With the improved efficiency of new delivery vectors, I think we’ll eventually get there—for some diseases, a true cure is possible.”
Exegenesis Bio’s SMA therapy is now in Phase 2 trials, building on earlier Phase 1 and 2 studies that demonstrated promising safety and efficacy. The company’s work in gene therapies for wet age-related macular degeneration has also advanced to Phase 1 trials.
KrASIA Connection features translated and adapted content that was originally published by 36Kr. This article was written by Hu Xiangyun for 36Kr.