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Patent
Warp Drive Bio | Date: 2016-09-30

The present disclosure provides methods and reagents useful for analyzing protein-protein interfaces such as interfaces between a presenter protein (e.g., a member of the FKBP family, a member of the cyclophilin family, or PIN1) and a target protein. In some embodiments, the target and/or presenter proteins are intracellular proteins. In some embodiments, the target and/or presenter proteins are mammalian proteins.


REDWOOD CITY, Calif.--(BUSINESS WIRE)--REVOLUTION Medicines, Inc., a company focused on frontier cancer targets and drug discovery inspired by nature’s lessons, today announced that noted chemical biologist and cancer investigator Kevan Shokat, Ph.D. has joined the company as an academic co-founder and member of the company’s scientific advisory board, along with co-founders Martin Burke, M.D., Ph.D. and Michael Fischbach, Ph.D. The company also appointed accomplished industry veteran Julian Adams, Ph.D., leading structural biologist John Kuriyan, Ph.D., and noted clinical and translational oncologist Trever Bivona, M.D., Ph.D., to its scientific advisory board. “REVOLUTION Medicines has established significant momentum in deploying our product engine to advance multiple oncology drug discovery programs,” said Mark A. Goldsmith, M.D., Ph.D., president and chief executive officer of REVOLUTION Medicines. “Dr. Shokat is a leader and pioneer in the design of small molecules to modulate signal transduction pathways that control cellular growth exploited by cancer cells. Drs. Adams, Kuriyan and Bivona are also exceptionally accomplished scientists who bring additional creativity, experience and insights to help us fulfill our mission to engage frontier targets on behalf of cancer patients.” Dr. Shokat currently serves as professor and vice-chair in the department of cellular and molecular pharmacology at University of California, San Francisco, professor in the department of chemistry at University of California, Berkeley and investigator at the Howard Hughes Medical Institute. He is the recipient of numerous awards and grants, including election to the National Academy of Science and the Institute of Medicine. Dr. Shokat and his research laboratory are widely recognized for exploiting tools of chemistry, protein engineering and genetics to reveal the functions of individual kinases within a cell, and thus identify critical signaling molecules as candidates for drug development. He is a founder of Intellikine (acquired by Takeda) and Cellular Genomics (acquired by Gilead); co-founder of Araxes Pharmaceuticals, eFFECTOR Therapeutics and Mitokinin, LLC and a scientific advisor at Kura Oncology. Dr. Adams currently serves as president, research and development at Infinity Pharmaceuticals. He is a highly successful and noted drug hunter, having discovered and developed Velcade® (bortezomib), a proteasome inhibitor for cancer therapy while at ProScript Inc. (acquired by Millennium Pharmaceuticals). Earlier in his career, while at Boehring Ingelheim, he discovered the drug Viramune® (nevirapine) for HIV. Dr. Adams has received many awards, including the 2012 Warren Alpert Foundation Prize for his role in the discovery and development of bortezomib, the 2012 C. Chester Stock Award Lectureship from Memorial Sloan-Kettering Cancer Center and the 2001 Ribbon of Hope Award for Velcade® from the International Myeloma Foundation. He is an inventor on more than 40 patents and has authored over 100 papers and book chapters in peer-reviewed journals. Dr. Adams is on the board of directors of Warp Drive Bio and the Princess Margaret Cancer Foundation, as well as a member of the scientific advisory boards of Cleave Biosciences and Stand Up to Cancer. Dr. Kuriyan currently serves as professor of biochemistry and molecular biology in the department of molecular and cell biology at the University of California, Berkeley. Dr. Kuriyan’s research focuses on the structure and mechanism of the enzymes and molecular switches that carry out cellular signal transduction. He is internationally recognized for his groundbreaking work in structural biology, including elucidation of foundational insights about the dynamics of protein kinases that have been highly impactful in the drug discovery field. He is an investigator at the Howard Hughes Medical Institute and member of the National Academy of Sciences, which awarded him the 2005 Richard Lounsbery Award. Dr. Kuriyan is an academic founder of Nurix, Inc. and a member of the advisory boards of Carmot Therapeutics and Amgen, Inc. Dr. Bivona is an associate professor at the University of California, San Francisco. He is a medical oncologist and accomplished cell and molecular biologist. He maintains an active academic clinical practice and leads a basic and translational research laboratory focused on cancer genetics, precision medicine and the molecular basis of targeted therapy response and resistance. Dr. Bivona’s research has led to the elucidation of important mechanisms of resistance to EGFR-targeted therapy, BRAF- and MEK-targeted therapy and ALK-targeted therapy in lung and other cancers. He is the recipient of an NIH Director’s New Innovator Award and an elected member of the American Society for Clinical Investigation. About REVOLUTION Medicines The mission of REVOLUTION Medicines is to discover and develop new drugs directed toward frontier oncology targets for cancer patients. The company draws inspiration from nature’s lessons including natural products that are inherently rich with biological function. REVOLUTION Medicines deploys an innovative toolkit including REVBLOCKS™, an integrated suite of modular synthesis methodologies applied to simple chemical “building blocks,” and the REVEAL™ computational platform, which uses evolution’s lessons to inform selection of chemical scaffolds and guide drug design for non-classical drug targets. Headquartered in Redwood City, Calif. at the intersection of Silicon Valley and the birthplace of biotechnology, REVOLUTION Medicines is a private company financed by top-tier investor Third Rock Ventures. For more information, please visit www.revolutionmedicines.com.


The invention features compounds (e.g., macrocyclic compounds) capable of modulating biological processes, for example through binding to a presenter protein (e.g., a member of the FKBP family, a member of the cyclophilin family, or PIN1) and a target protein (e.g., a eukaryotic target protein such as a mammalian target protein or a fungal target protein or a prokaryotic target protein such as a bacterial target protein). These compounds bind endogenous intracellular presenter proteins, such as the FKBPs or cyclophilins, and the resulting binary complexes selectively bind and modulate the activity of intracellular target proteins. Formation of a tripartite complex among the presenter protein, the compound, and the target protein is driven by both protein-compound and protein-protein interactions, and both are required for modulation of the targeted proteins activity. In some embodiments, the compounds of the invention re-program the binding of the presenter proteins to protein targets that either do not normally bind to the presenter protein (e.g., do not show detectable binding in mammalian cells absent the compound). In some embodiments, provided compounds re-program presenter protein binding to greatly enhance interaction with a particular target with which it may have some interaction absent the compound. Interactions achieved through such reprogramming result in an ability to modulate the activity of these new targets.


Patent
Warp Drive Bio | Date: 2016-08-02

Disclosed herein are methods for identifying novel drug candidates.


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.


News Article | August 12, 2014
Site: www.betaboston.com

Cambridge-based Tokai Pharmaceuticals is seeking to be the second local biotech firm with involvement from Harvard professor Gregory Verdine to go public this year, and the third overall. Tokai, a developer of a drug for prostate cancer, aims to raise $75 million in its initial public offering to fund clinical trials and develop new treatments. The company was founded in 2004 out of Apple Tree Partners in New Jersey, and based on research by Angela Brodie and Vincent Njar at the University of Maryland. Verdine was a co-founder of Tokai, but is not currently involved with the company. A professor of chemistry at Harvard, Verdine is serving as chief executive of Cambridge’s Warp Drive Bio and as a venture partner with Third Rock Ventures. Other biotech firms he has co-founded include Watertown-based Enanta Pharmaceuticals (IPO in 2013) and Cambridge-based Eleven Biotherapeutics (IPO in February). Tokai has raised at least $80 million in venture funding to date, most recently raising $35 million in mid-2013. Tokai’s top shareholders are Apple Tree Partners (49 percent of shares), Novartis BioVentures (28 percent of shares), and entities affiliated with Muneer Satter, formerly a partner with Goldman Sachs (11 percent of shares). The company’s lead drug candidate, galeterone, is targeted for patients with prostate cancer who aren’t being effectively treated by approved therapies, Tokai has said. The drug is currently in a Phase 2 clinical trial. Kyle Alspach has worked in journalism in Massachusetts since 2005 and was one of the original staff writers at BetaBoston. Follow Kyle on Twitter


News Article | February 20, 2015
Site: www.fiercebiotech.com

Sanofi has made official what's no longer news, trotting out Olivier Brandicourt as its next chief executive. Stepping in on April 2, the experienced Frenchman inherits a wealth of commercial challenges, a quixotic relationship with local regulators and a make-or-break pipeline the company believes can bring in $38 billion over 5 years. Brandicourt's bona fides are already well established. He has spent two years as head of healthcare at Bayer, before that serving a long stint in the top ranks at Pfizer ($PFE), and he's a physician by training. And, of course, he's French, ticking off an oft-ridiculed box on Sanofi's checklist for a new leader after it unceremoniously axed Canadian Chris Viehbacher last year. Now, taking the reins, Brandicourt joins a drugmaker working to keep a multitude of plates spinning, facing declining sales in its banner diabetes business, a handful of weighty near-term launches and a promising pipeline of in-development treatments with major expectations attached. On the latter score, Sanofi has promised to notch 18 new drug approvals over the next 5 years--up to 6 in 2015 and about one every 6 months from then on--and the drugmaker has gone out on a limb in saying its new products can bring in $38 billion over that same period. Such lofty goals require execution in the coming months, with the long-acting insulin Toujeo up for approval in the next few months and Praluent, a Regeneron ($REGN)-partnered antibody poised to lead a blockbuster market of new cardiovascular treatments, expected to win an FDA nod in August. And while Viehbacher remains non grata at Sanofi headquarters, the company has him and his penchant for checkbook research to thank for its late-stage pipeline. Under his watch, the company deepened its financial ties to Regeneron and Alnylam ($ALNY) without meddling in their innovation, pouring money into their R&D programs in exchange for commercial rights. And Sanofi kept its door open to small biotech, betting $125 million on Warp Drive Bio's microbial platform and $100 million on Voyager Therapeutics' approach to gene therapy, laying the groundwork for some moonshot bets on new technology. Whether Brandicourt plans to take the same approach to R&D will be something to watch. Beyond its long-delayed efforts to develop a dengue vaccine, Sanofi's internal development efforts have been largely anemic, and the company's moves thus far in 2015 paint a contrasting picture. Kicking off the year, Sanofi cut about 100 researchers at its Genzyme unit and backed away from its as-yet-unproductive work in oncology, but only after pairing up with Voyager in a deal worth up to $845 million. The new CEO has yet to make any public pronouncements on his plans, but Sanofi Chairman Serge Weinberg said in a statement that Brandicourt's "strong experience combined with his international profile, deep knowledge of U.S. and emerging healthcare markets, and his capability to unite teams will provide new dynamism to Sanofi's strategy of diversification and innovation." Related Articles: Sanofi drops the ax on 100 R&D staffers in Boston reorganization Sanofi embarks on an $845M gene therapy R&D odyssey with Voyager Sanofi sticks to Viehbacher's R&D script as it rolls out a $38B pipeline vision


News Article | November 29, 2016
Site: www.businesswire.com

CAMBRIDGE, Mass.--(BUSINESS WIRE)--Warp Drive Bio, Inc., a life sciences company developing therapeutics that exploit the molecules and mechanisms of nature, announced today that it has reached a pre-specified milestone in the antibiotic discovery program within the company’s research collaboration with Sanofi. From here, Sanofi will assume all preclinical and clinical research and development efforts for the novel aminoglycoside antibiotic candidates that have been discovered by Warp Drive. Th

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