With the takeover of Fluorinov Pharma Inc. comes a set of preclinical oncology compounds plus a fluorine-chemistry platform that "we can use to crank out new chemical entities [NCEs] to just about any target that seems promising," Trillium Pharmaceuticals Inc. CEO Niclas Stiernholm told BioWorld Today, explaining about his firm's decision to pay C$10 million (US$7 million) up front, plus as much as C$35 million if clinical and regulatory milestones are met with any of the existing candidates.

Those candidates include orally available bromodomain and proteasome inhibitors, as well as epidermal growth factor receptor (EGFR) antagonists. Trillium will acquire all of the outstanding shares of Fluorinov. Having switched from transplant work to immuno-oncology around 2003, Trillium said the firm is transforming by way of the bounty-bringing Fluorinov arrangement. Both firms are based in Toronto.

The carbon-fluorine bond, strongest in organic chemistry, is widely used to block sites of metabolism and improve drug half-life, boosting potency, selectivity, tissue penetration, half-life and stability. One company, Scifluor Life Sciences LLC, of Cambridge, Mass., founded its approach on adding fluorine to approved drugs and compounds in clinical development to create NCEs with improved pharmacologic profiles. (See BioWorld Today, Oct. 26, 2012, and April 24, 2015.)

With Fluorinov, "the bromodomain inhibitor [program, FV-281] really intrigued me," Stiernholm said. "I started to read about these things and how a lot of the epigenetic modifiers are thought to be good candidates to combine with checkpoint inhibitors, and I thought, this could actually fit," though he conceded that his background in immunology meant "it took some time for me to get there." The company's compounds are "very close" to investigational new drug application-enabling studies, he said.

Earlier this month, Basel, Switzerland-based Roche AG snatched up bromodomain and extra terminal domain inhibitor specialist Tensha Therapeutics Inc. in a deal worth up to $535 million. Tensha, of Cambridge, Mass., had a phase II trial in triple-negative breast cancer set to begin shortly, and results already have been disclosed against nuclear protein in testis midline carcinoma. (See BioWorld Today, Jan. 11, 2016.)

Stiernholm also pointed to the late 2014 deal in which Kenilworth, N.J.-based Merck & Co. Inc. bought bromodomain inhibitor-focused Oncoethix SA, of Lausanne, Switzerland, for $110 million up front and $265 million in potential milestone payments. Oncoethix had oral OTX015 in phase Ib trials for hematological malignancies and advanced solid tumors. (See BioWorld Today, Dec. 19, 2014.)

CASH POSITION STRONG

Another area with possibilities cited by Stiernholm and enticing to pharma: A2A adenosine receptor (A2AR) antagonists. Last August, Heptares Therapeutics, a subsidiary of Tokyo-based Sosei Group Corp., collected $10 million up front and potentially more than $500 million in milestones by out-licensing to Astrazeneca plc its A2AR antagonist HTL-1071 for development in immuno-oncology indications. It would also receive tiered double-digit royalties on product sales. This is the same compound that Heptares, of Welwyn Garden City, U.K., licensed to Dublin-based Shire plc in 2012 for disorders of the central nervous system (CNS), in a deal worth up to $190 million in milestone payments. (See BioWorld Today, March 21, 2012, and Aug. 7, 2015.)

In the Fluorinov takeover, EGFR research especially piqued Stiernholm's interest after the bromodomain push. "I worked with EGFR back in 2000 when I was with YM Biosciences [Inc.]," he said. "It's an old target but a validated target. What excited me there was the increased uptake in the brain," so that the compound might work against tumors there. At the end of 2012, Foster City, Calif.-based Gilead Sciences Inc. bought YM in a transaction Gilead valued at $510 million. (See BioWorld Today, Dec. 13, 2012.)

"EGFR is clearly a good target in glioblastoma," Stiernholm said. "The problem is that you can't get enough drug in there, or enough drug to stay there," he said. Fluorinov has been advancing FV-240, described as a brain penetrant that could be a next-generation erlotinib (Tarceva, Roche AG). So far, FV-240 seems to maintain erlotinib subnanomolar potency and high kinase selectivity, as fluorination increases target organ exposures vs. erlotinib and "takes classical EGFR therapy into the brain," according to a presentation on Trillium's website.

Least thrilling of the Fluorinov bunch for Stiernholm is the oral proteasome inhibitor program with FV-162. "Speaking to some of my clinician friends, I don't know how much enthusiasm there is," he said. "I hope I'm wrong, but I haven't really decided what to do with that asset. I still need to figure out with key opinion leaders if this is something that would excite them." He said his sense is that the ardor of several years ago for such compounds has waned. Still, the compound's data suggest "excellent tolerability should be achieved by continuous low-dose therapy given the myeloma therapeutic window," according to the Trillium presentation.

"My current thinking, and these things always can change, is that we will be driving [the bromodomain program] on our own and maybe partner the EGFR campaign" after conducting brain imaging to confirm the uptake recorded by Fluorinov, Stiernholm said. "It's possible we could use some help on that one."

Formerly known as Transplantation Technologies Inc., Trillium changed its name in May 2003 to reflect its new emphasis in immuno-oncology. The trillium is the official flower of Ontario, and from that province hail academics from six institutions on whose research the company is based. Stiernholm, who came to Trillium in late 2002, called the Fluorinov deal "a fairly low cash-intensive effort" that will "not significantly impact our financing plans or burn rate." Trillium raised $55 million in April and "we're not looking to raise money this year," he said. "We have about $60 million in the bank, and we anticipate a burn rate of $20 million per year. We're in good shape."

Shares of Trillium (NASDAQ:TRIL) closed Wednesday at $8.92, down 16 cents.