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Vucic E.A.,British Columbia Cancer Research Center | Vucic E.A.,University of British Columbia | Thu K.L.,British Columbia Cancer Research Center | Robison K.,Warp Drive Bio | And 7 more authors.
Genome Research | Year: 2012

The genomics era has yielded great advances in the understanding of cancer biology. At the same time, the immense complexity of the cancer genome has been revealed, as well as a striking heterogeneity at the whole-genome (or omics) level that exists between even histologically similar tumors. The vast accrual and public availability of multi-omics databases with associated clinical annotation including tumor histology, patient response, and outcome are a rich resource that has the potential to lead to rapid translation of high-throughput omics to improved overall survival. We focus on the unique advantages of a multidimensional approach to genomic analysis in this new high-throughput omics age and discuss the implications of the changing cancer demographic to translational omics research. © 2012 by Cold Spring Harbor Laboratory Press.

Cui M.,California Institute of Technology | Siriwon N.,California Institute of Technology | Siriwon N.,University of Southern California | Li E.,California Institute of Technology | And 3 more authors.
Proceedings of the National Academy of Sciences of the United States of America | Year: 2014

Wnt signaling affects cell-fate specification processes throughout embryonic development. Here we take advantage of the well-studied gene regulatory networks (GRNs) that control pregastrular sea urchin embryogenesis to reveal the gene regulatory functions of the entire Wnt-signaling system. Five wnt genes, three frizzled genes, two secreted frizzled-related protein 1 genes, and two Dickkopf genes are expressed in dynamic spatial patterns in the pregastrular embryo of Strongylocentrotus purpuratus. We present a comprehensive analysis of these genes in each embryonic domain. Total functions of the Wnt-signaling system in regulatory gene expression throughout the embryo were studied by use of the Porcupine inhibitor C59, which interferes with zygotic Wnt ligand secretion. Morpholino-mediated knockdown of each expressed Wnt ligand demonstrated that individual Wnt ligands are functionally distinct, despite their partially overlapping spatial expression. They target specific embryonic domains and affect particular regulatory genes. The sum of the effects of blocking expression of individual wnt genes is shown to equal C59 effects. Remarkably, zygotic Wnt-signaling inputs are required for only three general aspects of embryonic specification: the broad activation of endodermal GRNs, the regional specification of the immediately adjacent stripe of ectoderm, and the restriction of the apical neurogenic domain. All Wnt signaling in this pregastrular embryo is short range (and/or autocrine). Furthermore, we showthat the transcriptional drivers of wnt genes execute important specification functions in the embryonic domains targeted by the ligands, thus connecting the expression and function of wnt genes by encoded crossregulatory interactions within the specific regional GRNs.

News Article | January 10, 2012
Site: www.xconomy.com

Warp Drive Bio Launches With $125M from Third Rock, Greylock, Sanofi Today a new company called Warp Drive Bio is starting up in Cambridge, MA, with a simple and powerful premise: Mother Nature may be the best source of blockbuster drugs—if only we can find new methods for unlocking her secrets. Warp Drive’s plan is to use genomics technology incubated at Boston-based Third Rock Ventures to discover new “natural products,” which are therapies derived from plants, animals, and other wild organisms. Warp Drive is being launched with $125 million in funding from Third Rock and French pharmaceutical giant Sanofi (NYSE: SNY). Greylock Partners also participated in the financing. Warp Drive was co-founded by Greg Verdine, a Harvard University chemical biologist and venture partner at Third Rock, along with Harvard University genomics expert George Church, and biolochemist James Wells of the University of California at San Francisco. The startup’s business model is distinctive in that Warp Drive will remain fully independent. It will retain rights to many of the assets it develops, and even have the freedom to pursue other partnerships beyond its Sanofi alliance. The funding is tranched, and contingent upon Warp Drive reaching milestones in developing the technology and proving it works. Perhaps what’s most unusual about the deal is that it’s set up to ensure that Sanofi will acquire Warp Drive if certain milestones are reached. “Sanofi doesn’t just have the option to buy, they have the obligation,” says Alexis Borisy, a Third Rock partner (pictured at right) who is serving as interim chief executive officer of Warp Drive. “That decreases the financing risk for Warp Drive, and it decreases the liquidity risk for the VCs. We’re not at the whim of the IPO market.” Warp Drive refers to its core platform as a “genomic search engine.” The company’s ultimate goal is to develop the technology to the point where it will be able to comb through naturally derived substances—such as plants and soil—and sequence the genomes … Next Page »

News Article | October 7, 2013
Site: www.xconomy.com

If you’re a tenured biomedical researcher at a university today, and you have a big idea for what could be a new drug or diagnostic test, you can do a couple things. Hand it off to someone else at a startup, keep your day job, dabble as an advisor for a couple hours a week at most, and hope for the best. Or, you can give up the security and perks of the university, risk your academic career, and dive into the all-consuming startup life. Then hope for the best. For most people, that’s a no-brainer. Most tenured faculty keep their day jobs, and never plunge into the hard work of trying to turn a concept into a product that benefits patients. That’s why what Greg Verdine is doing is so interesting. Verdine is a world-class chemical biologist at Harvard University. A couple years ago, he founded a startup that attracted big investment from Third Rock Ventures and Paris-based Sanofi, the pharmaceutical giant. For the first 18 months or so, Verdine did the usual thing. He kept his tenured academic day job, while overseeing science at the company, Warp Drive Bio, on the side. Earlier this year, Verdine agreed to dive into Warp Drive full-time for a while to see if it can deliver on its promise to create new drugs. He needed to take an unusual risk to do this. He gave up his tenured faculty position at Harvard to run the company as CEO, for an expected period of about three years. In consultation with university officials, he agreed to keep running his 15-person lab at Harvard on a part-time basis during his stint in industry. Verdine’s plan is to then hopefully come back to Harvard as a ‘professor in the practice’ who teaches and does research, but works on a five-year renewable contract instead of a tenure deal. If things don’t work out at Warp Drive, or even if they do and he just wants a new challenge after a while, he can always fall back on that. This kind of career path makes a lot of sense to me. It certainly comes with its complications. Any university that grants a long leave to a faculty member will need to find someone to pick up the slack on research and teaching. People will also inevitably wonder about whether a faculty member’s business interests will get in the way, and tempt them to exploit the resources of the university for private gain. It’s a legitimate concern, but universities have been dealing with this tension for a long time, and there are ways to manage conflicts of interest so that each side can get what they want. To be sure, Verdine isn’t the first faculty entrepreneur who has sought to play in both the worlds of business and academic research. Elias Zerhouni, the president of global R&D at Sanofi, says he did a similar thing earlier in his career when he was at Johns Hopkins University and felt compelled to ask for—and get—a two-year leave of absence to pursue an entrepreneurial dream. Zerhouni, who helped create Warp Drive Bio with Verdine, sees a lot of potential for other entrepreneurial faculty members to follow this kind of career path. “You can point to the ‘purity of this, or the purity of that’ in going to industry, but for him to advance his idea, it might have taken him 15 years at Harvard,” Zerhouni said, during a recent Sanofi event in Cambridge, MA. “Here [at Warp Drive Bio], it will take him two years to see if it will work. He can recruit grad students, postdocs, and others fast. He doesn’t have to go through all the things you have to go through at a university. It’s the right thing to do.” “When you have an innovator, give him a chance. Why not?” Zerhouni said. “I really believe if Greg succeeds, it will be a revolutionary accomplishment.” I agree, this is an important experiment that scientific entrepreneurs everywhere should keep an eye on. But I sense the optimistic view isn’t widely shared by university administrators. Many are afraid that they’ll mess this up, and wake up to read a newspaper one day with a scandalous headline that says ‘University Researcher Exploits Taxpayer-Funded Research, Poor Young Grad Student Wage Slaves, to Become Mega-Millionaire Yacht Owner” or something like that. They aren’t nearly as afraid of a headline that says “University Researcher Pocketed Millions of Taxpayer Dollars and Never Bothered to Try to Develop Drug Because of Outdated HR Policies.” Yet if they allowed faculty to pursue more entrepreneurial dreams, it wouldn’t cost much, and it has potential to do a whole lot of good that the university could brag about forever. I had a lively conversation recently with Verdine about his unusual career plan, during a visit to Warp Drive Bio’s office in Cambridge, MA. Here are edited excerpts: Xconomy: How did you get started on Warp Drive Bio? Greg Verdine: I was talking with Elias, and he said he wanted … Next Page »

News Article | April 15, 2013
Site: www.xconomy.com

The need for innovation in healthcare has arguably never been greater.  A range of factors, from aging world populations to rising standards of living in developing countries, are poised to drive long-run demand for innovative drugs, devices and medical technologies that can improve outcomes and reduce costs. Ironically, however, funding for healthcare innovation remains in short supply.  As industry participants are keenly aware, life science venture capital financing – which has played a critical role in helping translate research ideas into commercially useful medical technologies – is becoming increasingly scarce. Results from a recent survey of 2012 life science venture capital (VC) activity by Fenwick & West illustrate the magnitude of the situation.  The survey summarizes results from over 350 therapeutic, diagnostic and medical device financings occurring during 2012, and shows that financing valuations continued to trend modestly upward, evidence that companies are continuing to develop promising technologies that justify a step-up in valuation. However, fundraising by life sciences VCs has continued to decline.  While overall VC fundraising rebounded modestly during 2011 and 2012, the percentage of fundraising allocable to life science investments declined from 19 percent in 2009 to 12.5 percent in 2012.  In absolute dollar terms, estimated fundraising by life science VCs was $2.5 billion in 2012, compared to an average of $2.9 billion/year for 2009-11 and an average of $7.8 billion/year for 2007-08. Given these fundraising statistics, it should come as no surprise that 2012 saw the fewest first time venture financings of life science companies of any year since 1995, according to the MoneyTree Report.  Venture capitalists typically spend three or four years making new (first time) investments out of a fund, and then reserve the fund’s remaining capital for follow on investments.  So at this point, the 2008 vintage funds have stopped making new investments, and there are fewer new funds to fill the gap. In the face of this capital crunch – which appears likely to continue for some time – what is the aspiring life science entrepreneur seeking financing to do?  Plenty of smart people are giving thought to this topic, and the early stage financing ecosystem is evolving.  In the meantime, however, it’s helpful for entrepreneurs who plan to seek venture funding to bear in mind two simple and related points: 1. Recognize the timing mismatch: while life science technologies mature slowly, VC investment horizons are limited.  Venture capitalists, no matter how enthusiastic they may be about your technology, are constrained by fund structures that require them to return capital to their investors within ten years.  And practically speaking, VCs are often making investments several years into a fund’s life, and need to show returns to investors in order to raise their next fund as well.  The net result is that VCs are under considerable pressure to seek investments that can exit in five to seven years, ideally sooner. On the other hand, life science technologies – which invariably must navigate significant R&D and regulatory challenges – can take well longer than five, seven or even ten years to mature and demonstrate their full value. Adding to the challenge, today’s public markets are less receptive to development-stage life science companies, meaning that investors can no longer count on the possibility of an IPO to provide an exit opportunity.  Recent years (2011-12) have seen an average of 10 IPOs of venture-backed life science companies per year, in comparison to 25+ per year for 2004-07.  And as noted elsewhere – for example Fenwick & West’s IPO Survey – more than half of the life science companies that went public in 2011-12 priced below their target range. 2. Address the timing mismatch: increase your odds of raising venture financing by planning your business for exit from the outset.  Every thoughtful entrepreneur recognizes that investors need to see a path to “exit” their investment and realize a return.  However, there are key steps that can be taken – from the earliest stages of the business – to enable a quicker exit.  And in today’s capital constrained environment, going the extra mile and enabling a quicker exit is helpful, if not essential, to raising scarce venture funds. There are various ways to enable a quicker exit, for example: —Pursue technologies that can reach key value-inflection points sooner.  Resolve Therapeutics did this successfully, pursuing a lupus treatment where proof of mechanism could be established quickly using biomarkers. This helped the company go from research concept to a $255 million partnership and option deal with Takeda in little over two years. —Consider working with a corporate investor earlier.  Corporate investors are increasingly willing to work with life science companies from the earliest stages (for example, Novartis’ Option Fund), and can provide validation, invaluable feedback on market potential, and a possible path to exit.  As various industry observers have noted, companies with corporate investors involved tend to be more successful.  And in some cases, a potential sale to a corporate investor can be built in from the get-go, as done for example by Warp Drive Bio. —Adopt a business structure that permits tax-efficient sales of assets, prior to a sale of the entire business.  These structures, which typically involve a limited liability company or “brother-sister” corporations under common ownership, have been discussed in the industry for some time.  They are particularly well-suited to drug discovery platform companies, but can work with other business models as well, and have the virtue of allowing an earlier return of investor capital, de-risking the investment and improving overall investor IRR.  The key point for the entrepreneur to recognize, however, is that in order to avoid a potentially insurmountable tax cost, these structures must be implemented early, ideally at company inception. As supply and demand factors play out, the early stage financing ecosystem will continue to evolve.  Established pharma and device companies, disease foundations and other non-VC investors are playing an increasingly important role.  And perhaps in the not too distant future, big data analytics tools and digital health technologies to support better clinical trials will mature that can help shorten the cycle and reduce the cost of life science R&D.  But for entrepreneurs operating in the here and now, thoughtful early attention to the path to exit remains critical to raising scarce investor capital.

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