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Exclusive Interview: Dr. Sofie Qiao, CEO of Vivace Therapeutics

publication date: Jul 27, 2017
 | 
author/source: Richard Daverman, PhD

In June, Vivace Therapeutics burst its stealth bubble by announcing it had raised $40 million in venture capital. In fact, the San Mateo, California company had already been in existence for two years, but deliberately kept its public profile low -- invisible, actually. The reason? Its novel science. As Sofie Qiao, PhD, President and CEO of Vivace, told ChinaBio® Today in an exclusive interview, "We stayed covert; it was really early stage and novel; we wanted to see how it turned out." Vivace is targeting a known pathway to develop cancer drugs -- YAP. Two years ago, it wasn't clear the YAP pathway was druggable. Now, Vivace has generated potential YAP inhibitor molecules and moved into lead optimization. It also dropped the stealth mode.

Ten years ago, Dr. Qiao was CEO at LEAD Therapeutics, a company very similar to Vivace. Like LEAD, Vivace is virtual (just six employees currently); it is based in the US but uses China CROs for discovery and pre-clinical work; and it is developing an early stage cancer-targeted molecule. Like LEAD, Vivace aims at the "efficient use of capital" as it strives to "leverage the best people and science in the US and China."

Vivace got its start two years ago, when Dr, Qiao, then Managing Director of WuXi Ventures, was making the rounds, looking for interesting investments. She met two China-born scientists, who were collaborating even though they worked at different University of California schools: Sheng Ding, PhD, at UC San Francisco and Kun-Liang Guan, PhD, at UC San Diego.

Dr. Guan's lab was doing interesting work on a novel cancer pathway called YAP. Dr. Qiao noted the science hit a sweet spot for venture capitalists: "an oncogenic driver mutation story." It also offered the possibility of "Early in, early out," another lure for restless venture capitalists. The YAP pathway was implicated in many different cancer types -- that much was clear -- the problem was the pathway didn't have any obvious targets for small molecule drugs. In the words of Vivace's CSO Leonard Post, PhD, there was no obvious target to turn the pathway off.

China: It's Different Now

Despite the similarities, Vivace's situation is different from LEAD's, says Dr. Qiao. Ten years of China drug development progress have opened new avenues. "Leveraging the best of the US and China is broader than it was before. Now we are working on novel science," said Dr. Qiao, something that wasn't possible before. "At LEAD we were working on clinically proven targets for which we developed improved molecules. Back then, novel targets, novel science in China would have been very difficult," she declared.

Leonard Post, CSO of Vivace (and also CSO at LEAD), recalled what it was like ten years ago: "When we started LEAD, we were pretty sure we could do chemistry in China, but biology was not as clear. Literally, in my first visit to ChemPartner, the biology equipment was still in the boxes. They had it, but it wasn't unpacked. They were pretty sure they could make it work, but they hadn't done it yet. Now, leading China CROs such as WuXi AppTec are real powerhouses with all the technologies you need for drug discovery."

Investment is another difference. Much of the investment backing for Vivace is coming to the US from China, a common phenomenon today that wasn't even on the horizon ten years ago. Both WuXi Healthcare Ventures and Cenova Capital, which co- led the Series A and led Series B rounds respectively, are China-based, managed by China-born professionals with US pharma experience.

Plus, as Dr. Qiao says, "Vivace is built on the brain power of China as well as the US." The company's academic founders, who are responsible for the scientific breakthroughs that are the basis for Vivace's drug candidates, were all born in China, now educated and working in the US (also true for Dr. Qiao herself).

With its current portfolio of novel-science projects, Vivace's technology burden is higher. Vivace must have CROs that can elucidate the biology of its candidates, not just provide med-chem services. Capable academic labs are also an important part of the process. "At LEAD we didn't start working with academic labs until we had compounds that we were ready to take forward. Now, we are working with our three academic founders and their labs from the start. That's a key difference," said Dr. Qiao.

Programs in Development

Vivace's initial program is a group of YAP pathway-based inhibitors, based on research from the lab of Dr. Kun-Liang Guan. Until recently, the YAP pathway was known mostly for its role in controlling the size of organs, a signaling system that connects with other molecules. But YAP also becomes dysregulated and drives subsets of several cancer types.

By targeting different points in the pathway, Vivace expects to develop therapeutics that are effective in uveal melanoma, mesothelioma, liver, esophageal and ovarian cancers. Dr. Post points out that in each case, likely patients will be identified by the genetics of their tumors -- mutation in the YAP pathway -- rather than the tumor's histology. 

YAP as Immuno-Oncology Candidate

Up to this point, the drug development pathway for YAP was fairly straightforward, presenting problems along the way, but nevertheless following a normal drug development arc. However, in December 2016, the YAP story took an abrupt turn when Kun-Liang Guan's lab published an article in the academic journal Cell.

Dr. Guan was testing cancers that did not have the YAP mutation. He deleted the gene LATS 1/2 of the Hippo-YAP pathway, expecting to find that the deletion would create more aggressive tumors. Surprisingly, the opposite happened.

Dr. Post said, "In immuno-competent mice those LATS1/2 knockout tumors didn't grow. Dr. Guan did a lot of detective work to show that by activating the YAP transcription factor, it makes the tumor very immunogenic. That leads us to a small molecule strategy that fits into immuno-oncology if we can duplicate with small molecules what he did genetically."

That's potentially a big win for Vivace because the market for non-mutated-YAP cancers, using YAP to activate the immune system, is much larger than the market for YAP-mutated cancers. It reaches across larger subsets of many cancer types, used as a monotherapy or in combination with an immune checkpoint inhibitor.

BINspecific Antibodies

To diversify its portfolio, Vivace is also involved with BINspecific™ antibodies (bi-specific irreversible cell-type specific antibodies), developed in the lab of Bin Liu, PhD also a Professor at UC San Francisco and the third China scientific advisor at Vivace. So far, the company has disclosed it is working on this technology, though it isn't ready to give details, the stealth shroud still protecting the science.

But CSO Post did describe BINspecific antibodies as an intellectual concept: 'Dr. Liu has come up with a new way of thinking about bispecific molecules that tune the specificity and potency in a way that hasn't been done before. There are a lot of bispecific antibodies out there. This one is different. We vetted the science with expert input, and we concluded that this really is a different way of doing bispecific antibodies."

One project from the platform is being advanced. It is a project that Dr. Liu started in his lab and moved forward, though Vivace doesn't want to elaborate.

Vivace: Fast and Spirited

The word "vivace" is an Italian musical term meaning fast and spirited, a term the company uses to describe itself. They hope their lean virtual business structure, coupled with cost-effective China CRO work, will move its projects forward quickly and efficiently.

The company could, like LEAD Therapeutics did earlier, sell at a pre-clinical stage, though Dr. Qiao is fully aware of the critical inflexion points in drug development. "If we can generate greater value, then we want to do that," she said. "We are not against doing early stage deals as long as the economics make sense. But we have raised money so that we can get early clinical data."

With its $40 million of venture capital, Vivace expects it will be able to move some of its candidates into the clinic and get early reads on their viability. That might be the inflection point that the company seeks. Considering that Vivace is working with novel science and $40 million, it would also be validation that its capital efficient model works very well, indeed.

Disclosure: none.


 

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