Third Rock Ventures, LLC today announced the formation of REVOLUTION Medicines, Inc. with a $45 million Series A financing to discover and develop new therapies derived from natural products. REVOLUTION Medicines' innovative approach reconfigures these complex chemicals of life into best-in-class medicines. Veteran industry leader Mark A. Goldsmith, M.D., Ph.D., is the founding president and chief executive officer of REVOLUTION Medicines. Dr. Goldsmith brings to the company more than 25 years of experience as an academic scientist and senior executive in the biotechnology industry, and is a partner at Third Rock Ventures.

REVOLUTION Medicines builds upon the vision of the company's founder and scientific advisory board chairman, Martin D. Burke, M.D., Ph.D., professor of chemistry, University of Illinois at Urbana-Champaign, and Early Career Scientist of the Howard Hughes Medical Institute. Dr. Burke invented a transformative method for synthesizing original compounds that are pharmaceutically optimized analogues of complex natural products. The company has entered into an exclusive license agreement with the University of Illinois to practice and expand this technology, and is pursuing a rapid clinical development path with its lead antifungal program that originated in Dr. Burke's laboratory.

'With this major advance in chemical synthesis, we now have the opportunity to unlock the full medical benefits of natural products that have been selected through a billion years of evolutionary pressure,' said Dr. Goldsmith. 'Marty is a remarkably inventive chemical biologist, and REVOLUTION Medicines is working closely with him in his role as scientific advisory board chairman to exploit his breakthroughs for industrial-scale drug discovery through redesigning complex molecules. Our strategy should produce high-impact treatments for serious infections and non-infectious diseases, among them our lead product candidates for patients with life-threatening fungal infections.'

The arduous process of synthesizing natural products often requires years of trial and error to reconstruct a single chemical scaffold. In contrast, REVOLUTION Medicines' approach is a rapid, standardized and powerful process for assembling simple 'chemical building blocks' into refined natural product-like structures. These optimized compounds have significant potential as best-in-class drug candidates.

REVOLUTION Medicines' first drug candidates exploit and improve upon the properties of amphotericin B, a powerful, broad-spectrum antifungal compound found in nature that has avoided generating significant drug resistance in 50 years of clinical use. Full therapeutic benefit from this highly efficacious natural compound is significantly compromised by inherent dose-limiting side effects, principally kidney damage. Using the building block synthesis platform to create new molecules, Dr. Burke and his research group overturned decades of scientific dogma and demonstrated that the antifungal efficacy of the amphotericin B scaffold can be separated chemically from the major mechanism that underlies human kidney cell damage. REVOLUTION Medicines is developing novel compounds that leverage the proven therapeutic mechanism for killing fungi while minimizing toxic effects on human cells.

'Professor Burke and his group have demonstrated the power of research at our school to uncover methods and drug candidates that can be enormously impactful on human health,' said Phyllis Wise, Ph.D., chancellor of the University of Illinois at Urbana-Champaign. 'As one of the nation's original land-grant institutions, our mission at the University of Illinois at Urbana-Champaign is to serve the public good through learning, discovery and outreach. Third Rock Ventures has launched REVOLUTION Medicines to translate these discoveries into important human benefits.'

REVOLUTION Medicines Team

The REVOLUTION Medicines team brings deep expertise and a track record of building exceptional life sciences companies. In addition to Dr. Goldsmith, founding president and chief executive officer and Dr. Burke, founder and scientific advisory board chairman, the team includes: David Pompliano, Ph.D., founding chief scientific officer, who is a leading drug discovery and development expert who previously led infectious disease research at Merck and GlaxoSmithKline; Peg Horn, J.D., general counsel and senior vice president, corporate development, a seasoned corporate executive with extensive experience in small and large companies; Neil Exter, interim chief business officer, a member of REVOLUTION Medicine's board of directors and partner at Third Rock Ventures, who brings more than 20 years of experience leading business development and strategy, including service as chief business officer of bluebird bio (NASDAQ: BLUE) and Foundation Medicine (NASDAQ: FMI); and Alexis Borisy, a member of REVOLUTION Medicines board of directors, partner at Third Rock Ventures, and entrepreneur and chemical biologist who brings more than 20 years of experience launching and operating innovative science-based organizations, including Blueprint Medicines, Warp Drive Bio, Foundation Medicine and CombinatoRx.

Resources

Video: Dr. Marty Burke explains how his research group breaks down complex chemicals into simple 'building blocks'
Video: Dr. Marty Burke's research described at the 109th Meeting of the Advisory Committee to the Francis Collins, M.D., Ph.D., director of the National Institutes of Health (see time stamp 30:35)
Synthesis of most polyene natural product motifs using just 12 building blocks and one coupling reaction. Nature Chemistry 2014, 6, 484-491. E.M. Woerly, J. Roy & M.D. Burke.
C2'-OH of Amphotericin B Plays an Important Role in Binding the Primary Sterol of Human Cells but Not Yeast Cells. J. Am. Chem. Soc. 2013, 135, 8488-8491. B.C. Wilcock , M.M. Endo, B.E. Uno & M.D. Burke.
Amphotericin primarily kills yeast by simply binding ergosterol. Proc. Natl. Acad. Sci. U.S.A. 2012, Volume 109, 2234-2239. K.C. Gray, D.S. Palacios, I. Dailey, M.M. Endo, B.E. Uno, B.C. Wilcock & M.D. Burke.
About Third Rock Ventures

Third Rock Ventures is the leading healthcare venture firm focused on disruptive areas of science and medicine to discover, launch and build companies that make a dramatic difference in people's lives. By combining our team's scientific vision, strategic leadership, operational expertise and innovative deal-making capabilities, we nurture bold ideas that translate into successful business enterprises. Recognizing that the best way to create value for our investors is to create value for patients, our companies are built on a solid foundation of science, medicine, people and business strategy. For more information, please visit the firm's website at www.thirdrockventures.com.