BEIJING – U.S. biotech Tracon Pharmaceuticals Inc., of San Diego, has in-licensed from Chinese drugmakers 3D Medicines (Beijing) Co. Ltd. and Jiangsu Alphamab Biopharmaceuticals Co. Ltd. the rights to develop envafolimab, a subcutaneous PD-L1 antibody, to treat soft tissue sarcoma in North America.

Envafolimab was invented by Alphamab and is being co-developed with 3D Medicines. Known as KN-035 in Alphamab’s pipeline, envafolimab is potentially the world’s first subcutaneously injectable PD-L1 inhibitor to qualify as a best-in-class drug.

The companies did not reveal to BioWorld the amount of the up-front payment. Under the terms, Tracon will develop and commercialize envafolimab for its orphan indication. The license, which is exclusive and nontransferable, covers the U.S., Canada, Mexico and each of their dependent territories, where most of the clinical work will take place.

On the financial front, Tracon will bear the development costs, while 3D Medicines and Alphamab will supply the biologic for clinical trials and commercialization at pre-negotiated prices.

Tracon is also responsible for commercializing envafolimab for sarcoma. But if the drug is later approved for more indications in the U.S., Tracon could choose to co-market. If so, the two Chinese firms will be entitled to a royalty fee from Tracon, which stands at a teens-to-mid-double-digits percentage of the net sales of envafolimab and will be split at an undisclosed ratio.

But if the Chinese firms commercialize it, Tracon will receive the royalties, also in the same percentage range.

This is not Tracon’s first partnership with Chinese biotechs. In November 2018, it partnered with I-Mab Biopharma (Shanghai) Co. Ltd. to develop I-Mab's CD73 antibody TJD-5 and up to five bispecific antibodies in North America.

Global development strategy

Currently, envafolimab is undergoing a phase II trial for deficient mismatch repair/microsatellite instability high solid tumors and a phase III pivotal trial for biliary tract cancer in China. Alphamab expects to seek regulatory clearance for mismatch repair/microsatellite instability high solid tumors by the end of 2020 in the country.

To begin development in the U.S., Tracon plans to initiate a registration-enabling study of envafolimab in undifferentiated pleomorphic sarcoma (UPS) next year. UPS is the fourth most common soft tissue sarcoma that affects more men than women, accounting for around 10% of new cases of the rare disease in the U.S.

“Given the activity of other PD-1 and PD-L1 inhibitors in sarcoma, we believe a registration-enabling study of envafolimab in the sarcoma subtype of UPS will be meaningful to patients and providers,” said Tracon CEO Charles Theuer.

The U.S. biotech plans to discuss with the FDA the start a pivotal trial in UPS in early 2020. Its ultimate goal is to enable a biomarker-directed approach for treatment in patients with multiple types of soft tissue sarcoma.

“It’s an important step to push forward envafolimab in the U.S. as part of our global development strategy,” Alphamab CEO Ting Xu told BioWorld.

“We try to engage Tracon to leverage their clinical resources and particularly their infrastructure in sarcoma,” he said.

Through inking a pact with Tracon, Xu said envafolimab could be Alphamab’s first asset to enter the U.S. market by accelerating clinical development there.

But the pact with Tracon is only an extension of the current Alphamab-3D Medicine collaboration and will center only on sarcoma, Xu noted.

Under the current Alphamab-3D Medicine collaboration, envafolimab is in phase I trials in the U.S. and Japan for locally advanced or metastatic solid tumors.

Xu told BioWorld the two companies will soon initiate a pivotal trial in a major indication for the global market.

Alphamab is completing CMC and preclinical studies and is manufacturing envafolimab samples for clinical trials, while 3D Medicines designs, conducts and monitors clinical trials and trial data, reviews registration filings, and conducts global commercialization.

Envafolimab stands out in the PD-L1 space for its route of administration. To date, all approved PD-(L)1 inhibitors are intravenously administered, which requires frequent infusion services, increases the risk of infusion-related reactions, and may not be used in patients with limited vein access.

Compared to intravenous administration, subcutaneous injections offer advantages in safety, convenience, compliance, access to patients who are not suitable for intravenous infusion and lower medical costs.

“As the most advanced single-domain antibody in immune-oncology with the advantage of a subcutaneous dosage, we are confident it will provide a valuable option for cancer patients,” Xu said.

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