SHANGHAI – Hutchison Medipharma Ltd. (HMP) has gone from running a marathon to a sprint. HMP's pipeline has quickly grown from seven clinical trials to 16, 13 of which are phase Ib/II studies with 10 being in potential breakthrough therapy indications. This spurt of activity now puts HMP much closer to the finish line to deliver China's first world-class drug since artemisinin, an antimalarial that was discovered decades ago.

Founded 14 years ago, the R&D-focused company, which does all its preclinical work in China, has invested $255 million (with another $500 million invested from partners) on its pipeline of seven oncology and autoimmune candidates.

The company plans to file two new drug applications (NDAs) in 2016 with the CFDA and the FDA for small-molecule assets: Fruquintinib, an inhibitor of vascular endothelial growth factor receptors (VEGFR) being studied in colorectal cancer and non-small-cell lung cancer (NSCLC) and Savolitinib (formerly Volitinib, the name changed to be compliant with WHO rules), a c-Met tyrosine kinase inhibitor (TKI) being studied in multiple indications, namely kidney and gastric cancer.

There are a few factors at play enabling the company to more than double its number of clinical studies in one year and shave the timeline for filing NDAs.

First, both of these candidates are partnered with big pharma. Fruquintinib is partnered with Indianapolis-based Eli Lilly and Co. while Savoltinib is partnered with Astrazeneca plc, of London.

The company credits these partnerships, as well as others with Janssen Pharmaceuticals Inc. and Nestle Health Science SA, with accelerating the development of these candidates not only financially, but also via technical expertise and organizational resources. These deals generated $24.8 million in revenue for HMP in milestones and service income in 2014.

If all goes according to plan, the company stands to receive a further $471 million in future development and regulatory approval milestones; up to $145 million in further option payments and up to $560 million in commercial milestones.

The company also points to the large patient population in China. The speed of enrolling patients helped to make it more feasible to explore multiple indications in parallel, with more shots at the target they hope to gain a greater chance of success overall.

Just a few days ago HMP announced that it had completed enrollment for its proof-of-concept, placebo-controlled phase II study of Fruquintinib in 91 patients with non-squamous NSCLC who have failed second-line chemotherapy. The study's primary endpoint is progression-free survival, with secondary endpoints including disease control rate, overall response rate, overall survival and safety.

The company expects to release Fruquintinib's phase II results in NSCLC by this summer.

Fruquintinib is concurrently being studied in four trials. And beyond NSCLC, there are two trials ongoing for colorectal cancer.

In December, HMP kicked off a 400-person phase III registration trial in China testing 5 mg of Fruquintinib once daily in patients with colorectal cancer. With approval for phase II/III trial in hand, the company has taken a bold move to initiate a phase III at the same time as the phase II.

"On the colorectal side, we began a phase III registration study. We started enrollment last December ahead of the phase II readout. The reason we did that was based on very strong phase Ib data and the very high unmet medical need. We are moving ahead very aggressively on this phase III," Christian Hogg, CEO of HMP's parent company, Hutchison China Meditech Ltd. (Chi-Med), told BioWorld Asia.

The phase II colorectal study will release data by the end of March or early April. Top line results for the phase III are expected in 2016. (See BioWorld Asia, Dec. 17, 2014.)

SUZHOU FACTORY CONSTRUCTION UNDER WAY

In accordance with China's regulations for phase III trials and to get ready for market authorization, HMP is building a factory in Suzhou to produce Fruquintinib (along with Savolitinib) aiming to have it completed by the summer.

The Astrazeneca-partnered Savolitinib, which was designed to overcome the renal toxicity that caused other c-Met inhibitors to stumble, currently is being tested in a whopping eight indications, going after both overexpressed and amplified c-Met.

After three years of study, Savolitinib has shown partial response of >30 percent tumor reduction in patients with c-Met overamplification in kidney, lung, colorectal and gastric cancers. That is why HMP views it as having the potential to become a global first-in-class and best-in-class c-Met inhibitor.

The key opportunity is in kidney cancer, where c-Met is amplified in 40 percent to 75 percent of the patient population.

But the larger market opportunity is the 40 percent to 90 percent of patients with those tumor types (kidney, lung, colorectal and gastric) that have c-Met overexpressed.

The challenge facing HMP is that no c-Met TKI has shown clinical benefit for c-Met overexpressed tumors. Execs believe they have a chance however, given Savolitinib's ability to dose up to high levels (600 mg BID) with a good safety profile and high selectivity.

Either way, HMP's plan is twofold. If it is able to get the superior proof-of-concept data, the company will move into global trials, either on its own or partnered.

The company also has other candidates that fall under this strategy, such as Sulfatinib, for which it has filed for an IND with the FDA. Having shown a 32 percent objective response rate in neuroendocrine tumors, a far higher number then the current standards of care which hover in the low single digits, HMP has decided to take this candidate to the U.S. on its own. Sulfatinib is the first un-partnered therapy the company has taken to the U.S.

If a drug does not show global potential, HMP is prepared for that eventuality as well.

Since it already has a 3,000 person commercial operation in China as part of the China Healthcare division, the company can easily turn its focus to the China market. If a candidate shows non-inferiority when compared to existing global products, HMP will focus on bringing it to the China market at an accessible price.