SHANGHAI – China's most productive biosimilar developer, Suzhou Alphamab Co. Ltd., is deepening its biologics manufacturing footprint by setting up Alphamab (Jiangsu) Biopharmaceuticals Co. Ltd. – an export-focused plant in Suzhou. In spite of China's new market authorization holder (MAH) rules – permitting the use of contract manufacturing – Suzhou Alphamab is taking the plunge to invest heavily in the complex task of biologics manufacturing.
"Alphamab has an advantage in terms of process technology," Ting Xu, chairman and CEO of Suzhou Alphamab, told BioWorld Asia. "We started in 2009, mostly as a process development company and accumulated a lot of knowledge; we know how to make antibody proteins in an efficient and high-quality setting."
Since 2013, Suzhou Alphamab has been operating four lines of 250 liters and two lines of 1,000 liters.
The biopharma started out as a platform technology CRO and has licensed 20 biosimilars to Chinese pharmaceutical companies. One such deal with Chia-Tai Tianqing Pharmaceutical Group Co. Ltd. (CTTQ), for a biosimilar version of Pfizer Inc.'s Xyntha, a recombinant human coagulation factor VIII (rhFVIII), provided Alphamab with a $500,000 up-front payment, in a deal valued at $4 million. Out-licensing biosimilars has enabled Alphamab to remain largely self-funded on top of raising $20 million in 2011.
And biosimilar deal income has supported the development of their pipeline of more innovative candidates, including KN015, a long-acting human follicle-stimulating hormone (FSH) that replaces daily injections with one every 10 days. Last week, the CFDA gave KN015 the nod to enter the clinic. Suzhou Alphamab, is also the majority owner of Dingfu Biotarget, focused on immuno-oncology, it has 10 preclinical candidates disclosed including CD137 agonist, OX40 agonist, Mab-IFN hyerodimer and a CD27 agonist.
The farthest along is KN035, the first PD-L1 to file an IND in China, said Xu, who is hoping to get the clinical trial approval from the CFDA in the coming months.
As the parent company of the new biologics plant, Suzhou Alphamab plans to invest $50 million along with a handful of assets into the new manufacturing subsidiary. The entire project is valued at $300 million. The plan is to raise the remainder in a series A financing in the third quarter next year and to obtain an additional $100 million in debt financing.
Alphamab Jiangsu will produce biologics in commercial and clinical quantities, and will be geared toward producing for export to the U.S., as well as the domestic market.
Located in the Suzhou Industrial Park (SIP), Alphamab Jiangsu will be near the parent biopharma's R&D labs. There are also at least five other large biologics facilities in the area or in the process of being built: Jiangsu Hengrui Medicine Co. Ltd., Beigene Co. Ltd., Zai Labs, CP Guojian and Innovent Biologics Inc. (See BioWorld Today, July 22, 2015.)
The SIP remains a hot area for biopharma activity, so much so that finding and retaining employees can be difficult while those with manufacturing experience are considered among the most highly sought after.
"In Suzhou, we are competing with each other for talent. We are also competing with Shanghai and areas in Zhejiang. The talent pool is totally tapped," said Xu. However, the firm was able to nab Claudia Lin for the general manager role at Alphamab Jiangsu. Lin was vice president at Innovent Biologics, responsible for GMP compliance and quality management and led quality assurance divisions at Bayer Healthcare and Roche Holding AG's Genentech unit.
Xu was convinced the company had to set up its own commercial quantity manufacturing after it took longer than five months to find a CMO that would accept a project for manufacturing clinical quantities. Boehringer Ingelheim GmbH, considered the highest quality export-ready biologics maker in China, started building a facility before the MAH guidelines even permitted CMOs. Prescience aside, the firm is now racing to meet demand and some clients find themselves on long waitlists.
On the other end of the spectrum, many domestic pharma companies with deep pockets are building in-house biologics manufacturing before they have the pipelines to fill them.
Suzhou Alphamab's first candidate is entering the clinic in China, but Xu expects to have four more approved for testing in human subjects within the next six months (with one being tested in the U.S.). Xu said the risk of investing so much so early – two years ago the company also broke ground in Changchun for a plant that will make biologics for the domestic market – is manageable, given that the assets have a less risky value proposition centered on best-in-class differentiation (not first-in-class).
KN015 is a prime example. It is a long-acting formulation of FSH, a drug that is already approved in China with a market size of $330 million. The market is expected to grow rapidly as more couples can afford optional treatments. In China, 18 percent of couples face fertility problems. FSH is used clinically for infertility treatment. In preclinical studies, KN015 showed longer in vivo half-life and similar bioactivity as compared to Gonal-F. Suzhou Alphamab plans to develop KN015 in China and the U.S.