Rexahn Pharmaceuticals Inc., of Rockville, Md., has granted Biosense Global LLC an exclusive license to develop and commercialize the chemotherapy RX-3117 in pancreatic cancer and up to three additional cancers in greater China. The deal, which delivers Rexahn $3 million up front, could be followed by up to $226 million in development, regulatory and commercial milestone payments from Biosense.

News of the deal lifted shares of Rexahn (NYSE:RNN) by 25.3 percent to $6.74 on Tuesday, reflecting investor enthusiasm for a transaction that Rexahn President and CEO Douglas Swirsky told BioWorld will provide "meaningful and achievable milestones during the development phase."

The agreement is the third of its kind for Biosense, following deals with Seoul-based Chong Kun Dang (CKD) Pharmaceutical Corp. and Neovacs SA to license rights to interferon-alpha kinoid for the treatment of lupus in South Korea and greater China, respectively. Founded in 2017 with offices in East Rutherford, N.J., and Suzhou, China, Biosense has also invested in four early stage U.S.-based companies developing products with the potential to address unmet needs in China, Andy Li, president and CEO of Biosense Global, told BioWorld. (See BioWorld Today, Feb. 23, 2017.)

Li said he and his team chose to invest in RX-3117 due its proven target, unique mechanism of action, and the potential to provide a strong replacement for gemcitabine (gem). In addition, he said the drug may offer additional benefits, such as efficacy for patients with resistance to gem or who do not respond to the widely used chemotherapy and the flexibility to be delivered either orally or via I.V.

Li previously held management positions at Glaxosmithkline plc, Abbott Laboratories and most recently, Daiichi Sankyo Co. Ltd., during which time he helped introduce Humira (adalimumab, Abbvie Inc.) and Olmesartan (olmesartan medoxomil) to China.

Cancer is the leading cause of death in China, with more than 4 million new diagnoses and almost 3 million deaths per year, and "despite the significant success of immunotherapy, chemotherapy will remain a critical component of treatment regimens for many cancers," the companies said.

An oral small-molecule nucleoside, RX-3117 is intracellularly activated (phosphorylated) by the enzyme uridine cytidine kinase — also known as 'UCK2' — where it is incorporated into the DNA or RNA of cells and inhibits both DNA and RNA synthesis, inducing apoptotic death of tumor cells. UCK2 is overexpressed in a number of human tumors, but it has a very limited presence in normal tissues.

The candidate is currently being studied in a phase IIa trial in combination with Abraxane (nab-paclitaxel, Celgene Corp.) in first-line metastatic pancreatic cancer patients and in a phase IIa trial in patients with advanced or metastatic bladder cancer. The bladder cancer program is unlikely to move forward due to recent developments in that indication, such as the approval of Janssen Pharmaceutical's Balversa (erdafitinib), Swirsky said. (See BioWorld, April 15, 2019.)

Rexahn may also move to deprioritize RX-5902, an orally administered modulator of the beta-catenin pathway, which its team has been studying in combination with Keytruda (pembrolizumab, Merck & Co. Inc.), Swirsky said. A trial of the combination has not yet started.

By contrast, the pancreatic cancer study testing RX-3117 and Abraxane is cruising ahead, with expectations for an initial readout later this year. The Biosense deal will support not only further testing of the candidate in China, but also the potential expansion of its application to additional oncology indications that Rexahn doesn't currently have the resources to support.

Swirsky said the developments are all part of ongoing improvements at the company, which included a late-2018 restructuring, the addition of experienced board members, and his appointment as president and CEO in November 2018. If the company's Biosense bet pays off, the deal will yield not only milestone payments but tiered royalties on sales of the drug, too.