CEO Sofie Qiao told BioWorld that Vivace Therapeutics Inc. can "probably get into the clinic in the next couple of years" with its lead program – an inhibitor that operates in the Hippo-YAP signaling pathway – thanks to $25 million raised in a series B round. The money supplements $15 million garnered by way of the series A financing in 2015, when the San Mateo, Calif.-based firm was founded.

"We're not giving a lot of details" about the program, said Chief Scientific Officer (CSO) Leonard Post. "On the other hand, we're saying we do have antagonists that we think [show] the kind of activities we would expect. We don't claim that they're drugs yet, but we've seen enough." The pathway, recognized for years, involves transducing "signals from the surface of the cell to activate a particular gene expression program, and in YAP that is a transcription factor that turns on these particular genes," he said. "It doesn't do a lot, apparently, in normal cells, but it's activated in [cell] development and wound healing and certain situations, and there are tumors that have mutations that activate the pathway at all different levels.

There are no obvious targets to inhibit the pathway, so we had to try a variety of things to get to the point that we were confident" about the approach. "There aren't any [other candidates] very far along in development, as far as we know," he added.

Vivace's scientific co-founder, Kun-liang Guan, of the University of California in San Diego, recently discovered potential immuno-oncology applications by activating the pathway as well, so the company is working from both ends. Hippo controls cell proliferation and apoptosis. YAP, or yes-associated protein, is implicated in various cancers, including hepatocellular, ovarian and non-small-cell lung.

The company is also exploring bispecific irreversible cell-type specific antibodies that bind to target cells. Discovered in the laboratory of another co-founder, Bin Liu, of the University of California in San Francisco, the antibodies derive from a platform that Vivace said can achieve "super-potent inhibition" and cellular selectivity of specific targets, creating a superior therapeutic index. New investor Cenova Capital led the series B round, which included Sequoia Capital China and existing investors Canaan Partners, Wuxi Healthcare Ventures (where Qiao was a managing director), and Mission Bay Capital. Canaan Partners and Wuxi Healthcare Ventures co-led the series A.

With six employees, Vivace takes its name from an Italian term, pronounced "viv-OTCH-ee," that in classical music means to play in a brisk, spirited way. "To the extent possible, we intend to stay virtual, but it doesn't mean we won't add new team members as the need arises," Qiao said. The goal of the company is to pair science with strong researchers from the U.S. and China. Pairing "people who have worked together before in similar settings" is important, too, she said. "We want to make sure that we minimize risk on all fronts as much as possible."

Doing deals 'judiciously'

Qiao and Post co-founded Lead Therapeutics Inc., of San Bruno, Calif., which completed its series A in 2007 and was acquired in a potential $100 million deal in 2010 by Biomarin Pharmaceutical Inc., of San Rafael, Calif., "mostly for [Lead's] poly ADP-ribose polymerase [PARP] inhibitor," then in preclinical development," she said. "After a couple of acquisitions, it's in Pfizer's hands" and has reached the phase III stage. Known at the time of the buyout as LT-673, talazoparib made a good showing at this year's meeting of the American Society of Clinical Oncology (ASCO), where the New York-based pharma firm offered phase II data showing the drug had activity in patients with germline (inherited) BRCA1/2-positive advanced breast cancer. CSO Post called talazoparib "quite different from the other [PARP inhibitors] out there." (See BioWorld Today, Feb. 8, 2010.)

Others agree. In the summer of 2015, San Francisco-based Medivation Inc. inked a deal to pay $410 million up front for global rights to talazoparib. The asset purchase agreement included $160 million in milestones and mid-single-digit royalties for Biomarin on net sales of products that contain talazoparib during the deal's undisclosed royalty term. In return, Medivation gained all talazoparib-related assets including all patents, data, know-how, third-party agreements, regulatory materials and inventories. Then-Medivation CEO David Hung talked up the drug, calling it "a multibillion-dollar opportunity," as Paris-based Sanofi scratched at Medivation's door for a potential takeover. Hung referred to possible "best-in-class" performance due to what he said was talazoparib's superior ability to trap PARP protein on DNA, and hinted that the company might reduce the target number of events in its pivotal breast-cancer trial, EMBRACA, to enable a nearer readout. A month later, Pfizer stepped ahead of Sanofi, pledging $14 billion, and won the day. (See BioWorld Today, Aug. 25, 2015, July 8, 2016, and Aug. 23, 2016.)

PARPs are hot. Also at this year's ASCO meeting, detailed results from the phase III OLYMPIAD trial testing London-based Astrazeneca plc's Lynparza (olaparib) in BRCA-related metastatic breast cancer were featured in the plenary session. The OLYMPIAD experiment in about 300 women showed that the drug, compared to chemo, reduced the chance of progression of advanced, BRCA-related breast cancer by 42 percent, delaying progression by about three months. (See BioWorld Today, June 6, 2017.)

Asked what might lie ahead for Vivace, Qiao said that, "with the financing, clearly we don't want to be sold as early as, say, Lead Therapeutics. That being said, we will entertain business development inquiries, and we will do deals judiciously." She left open the prospect of "an offer I cannot refuse. M&A and IPO are both possible exits, but it's too early to talk about it. We're still busy executing our programs."