HONG KONG – Shanghai Miracogen Inc., a Chinese startup focused on developing antibody-drug conjugates (ADCs) against cancer, introduced technologies from Dutch firm Synaffix BV to co-develop a potential best-in-class ADC product. Under the licensing agreement, valued up to $125 million, Miracogen will obtain nonexclusive rights to Synaffix's Glycoconnect and Hydraspace ADC technologies for use on its next clinical candidate.

Miracogen will handle research, development, manufacturing and commercialization, while Synaffix will manufacture the components related to its Glycoconnect and Hydraspace technologies.

"We plan to file an IND in the U.S. and China in the second half of next year," Mary Hu, CEO of Miracogen, told BioWorld regarding the co-developed drug candidate.

She said Miracogen execs met with Synaffix last year at a conference in Shanghai and became interested in the latter's site-specific conjugation technology. Both companies then signed a material transfer agreement.

"Synaffix helped us generate some ADC material on one of our antibodies. We then performed efficacy studies using in vitro cell-based assays and xenograft mouse models," she explained. "Greater efficacy and wider therapeutic window were observed. That's why we'd like to introduce this technology into our new antibodies and our next program."

Synaffix's Glycoconnect is the conjugation technology that exploits the native glycan for site-specific and stable payload attachment. Hydraspace is the compact and highly polar spacer technology. Both technologies can be used on existing antibodies without any protein engineering, and they are compatible with all ADC payload classes.

With a name suggesting the word "miracle," Miracogen is aiming to bring miracle drugs to cancer patients. Hu is an American-trained biotech scientist who once worked at global giant Glaxosmithkline plc and ADC pioneer Seattle Genetics Inc. She returned to China to establish her own startup in 2014.

"We currently have two assets in phase I studies. We hope to move them into phase II trials in the next 12 months," Hu said.

The company's lead program, MRG-003, is an anti-EGFR ADC for treating colorectal cancer and head and neck cancer. Hu said it could be a best-in-class drug and has already shown great promise. Miracogen hopes to push it into phase II trials in a year or so.

The other asset in phase I testing is MRG-002, an anti-HER2 ADC to treat gastric cancer and breast cancer.

In earlier development is anti-CD20 candidate MRG-001, which will enter clinical trials soon for treating non-Hodgkin lymphoma. "We got our third IND approval in February 2019. We are now preparing GMP materials and hope to see the first patient dosed in May or June," Hu said.

Miracogen has three more preclinical candidates in its pipeline, all intended for treating solid tumors.

Hu noted that the regulatory reform of China's National Medical Products Administration (NMPA) has helped the firm score IND approvals faster than expected.

"The first one took us 14 months to get, then the second one seven months, and the third one five months only. We hope that our fourth IND approval can come in 60 days as the NMPA has promised," she said.

Cancer rate growing in China

Having a few promising drug candidates under its belt, Miracogen secured ¥350 million (US$52 million) in a series A financing round in July 2018.

"We've been lucky in getting investment. A lot of venture capital firms have already approached us for the next round of financing," Hu said.

"Our corporate leadership all came from the U.S. and we're U.S.-trained, working in the pharmaceutical industry for 20 some years," she said, with regard to her colleagues Maggie Li and Hu Li.

Maggie Li, who is responsible for regulatory strategies and product registration, previously worked at Cell Therapeutics Inc., Seattle Genetics and Acucela Inc. in the U.S., with global regulatory affairs focus and expertise on IND and NDA applications.

Hu Li, vice president of preclinical biology at Miracogen, worked for GSK for 19 years in drug early development.

"We now have 45 people in the company. Other than the executives, we also have scientists returning from the U.S. or Hong Kong, with a doctoral or master's degree and experience working overseas," Hu added.

At the moment, Miracogen is collaborating with research institutes, universities and biotech companies in China, Europe and the U.S., actively extending its partnerships.

"Some companies that have an antibody platform have approached us for collaboration, and we are doing some feasibility study with one of the partners now. I hope we can have more deals within a year, and we are also looking for licensing opportunities," Hu said.

A China-born scientist, Hu said she decided to return to China after years working overseas to develop innovative cancer treatments for Chinese patients – and the timing seemed right. "The cancer incidence and death rate in China is growing rapidly," she said. "In contrast, in the U.S., the cancer rate actually dropped 27 percent over the past 25 years as indicated by a recent publication.

"If you look at the cancer epidemiology data in China, there were approximately 2.8 million deaths last year, meaning that over 7,000 patients died each day. It's stunning."

But, given abundant capital, policies favorable for innovation and a large talent pool, that can change.

"The capital investment in biopharma and biotech is really attractive in China. There was not a lot of venture capital 10 to 15 years ago in China. But things changed during the last five to 10 years, especially the last five years," Hu said. "For the last five years, China's pharmaceutical sector has been developing rapidly due to a large number of overseas returnees."

Chinese regulators also have introduced a lot of reforms, and joining the International Council of Harmonization in 2017 has changed the regulatory landscape dramatically, as it has enabled biotech firms to file INDs to develop innovative drugs in China.

Miracogen's ultimate goal is to bring safe, efficacious and affordable drugs to Chinese patients.

"Chinese patients really suffer, as effective drugs like PD-1, PD-L1 or other targeted therapeutics are not that affordable to the vast majority of them. We let the scientists be mindful of cost during the life cycle of drug development," Hu noted. "We need to achieve high quality and affordability."