BEIJING – Gene therapy startup Hui-Gene Therapeutics Ltd. Co., of Shanghai, said it secured more than ¥100 million (US$14 million) in a series A financing round to develop a safer gene therapy to treat genetic diseases caused by single-base mutations.

This round was led by CD Capital and supported by investors including Wuxi Apptec, Huimei Healthcare Management, Alwin Capital and existing investor Sherpa VC. The biotech secured ¥30 million from its angel investor Sherpa VC in November 2018.  

Established in October 2018, Hui-Gene has developed pipelines in neurodegenerative diseases, vision disorders and hearing impairments. It has two gene therapy candidates in the preclinical stage that it aims to push toward clinical testing and production.

Ensuring safety

The startup was co-founded by Hui Yang, a Massachusetts Institute of Technology-trained geneticist known for developing a method called GOTI to evaluate the off-target effects induced by gene editing tools. Gene editing is considered highly risky in biomed applications due to the issues of off-target edits.

GOTI stands for genome-wide off-target analysis by two-cell embryo injection, which is a method developed by Yang and other Chinese researchers to detect off-target mutations during gene editing.

“We want to get a higher fidelity with GOTI. We do not only focus on base editors, but all kinds of gene editing tools in order to have them validated by GOTI. Our goal is to use gene editing tools with the highest fidelity, then we can move to clinical applications,” Yang told BioWorld Asia. He is now leading the R&D team as chief scientific adviser.

He added that the current gene editing tools can cause a lot of side effects, so Hui-Gene hopes to optimize GOTI to minimize off-target effects and develop a better tool for editing genes.

In his research with other scientists, the team applied GOTI to both the Crispr-Cas9 and base editing (BE3) systems, the two commonly used gene editing tools, by editing one blastomere of a two-cell mouse embryo. They then compared whole genome sequences of progeny-cell populations at embryonic day 14.5.

Sequence analysis of edited and non-edited cell progenies showed that BE3 editing induced unwanted off-target single nucleotide variants (SNVs) at a rate 20 times higher than the spontaneous mutation rate, while SNVs were rare in embryos edited by CRISPR-Cas9.

In another study published by Nature, Yang said engineering deaminases could eliminate off-target effects.

Growing bigger and moving faster

With this new method to ensure the safety of gene editing, Yang decided to go from academia and into industry after years of laboratory work using gene editing in animals.

“If I want to use this technology to treat human diseases, I must establish a company to apply this directly in human patients. In China, there is no company or platform for translational medicine, so you must do it yourself,” Yang explained.

Yang works for the Institute of Neuroscience of Chinese Academy of Sciences, after receiving his training at the Academy’s biochemistry and cell biology unit and the Whitehead Institute for Biomedical Research at MIT.

He said his academic achievements have helped him convince the investors in the first round of funding. The recent FDA approval for gene therapies further encouraged Chinese investors to inject more funding into his startup.   

With more funding, Hui-Gene plans to advance its pipeline to IND, build a clinical-stage team and set up a GMP-level manufacturing facility. The startup already built a gene therapy R&D lab and a team of 30 researchers. It uses four technology platforms to develop its gene therapy candidates that cover gene editing technology, adeno-associated virus (AAV) technology for gene delivery, animal models that mimic human diseases as well as translational medicine and manufacturing.

Yang said the startup’s headcount could more than double next year, as it wants to handle R&D and AAV production on its own.

“We now focus on two diseases; blindness and spinal muscular atrophy (SMA),” Yang said, adding that the gene therapy candidate for treating blindness targets a toxic gene like RPE65.

China has yet to approve clinical trials for any gene therapy. Yang said Hui-Gene is working on going to clinical trials after the end of 2020 or in the next two years. The company has two candidates nearing IND stage, namely HG-001 for SMA and HG-003 for blindness. There are four other assets in the early development stage.

“Our strategy is to get an IND approval for gene expression first, then for gene editing,” Yang said. 

An area taking shape

Since gene editing is a new area, and the CRISPR baby scandal caused by Chinese scientist Jiankui He shocked the world last year, Chinese health regulators are extra cautious in dealing with this advanced technology to ensure its safety. It seems that there is a long way for Hui-Gene to go to achieve the trial green light it is aiming for.

That said, Yang sees that the regulators are trying to catch up with the latest tech developments and come up with a regulatory framework.

“Actually, they invited me to give them a lecture on gene editing and discuss how to regulate the technology, like what kind of quality control should be done before going to clinical application. They discuss with the scientists,” Yang said.

While regulations are still taking shape for the technology, Yang added that basic research in this space is budding as Chinese scientists are developing new gene editing tools and optimizing them.

He sees many opportunities to develop gene editing technology in China to advance its application in humans in the future.

“China has a lot of patients with rare diseases, so you can easily find patients for clinical trials,” said the hopeful scientist.

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