Where Einstein Meets Edison

Eleven Solutions to Biological Problems

Eleven Solutions to Biological Problems

May 4, 2010

A personnel driven (as opposed to intellectual property driven) approach to entrepreneurship and innovation.

University technology transfer officers are the gate keepers for the translation of many innovative technologies in biotechnology.  When spinning a company out of academic research, it is generally necessary to gain license of the intellectual property associated with the research, providing freedom to operate in the technological space.  Each year, the MIT technology licensing office earns tens of millions of dollars in revenue from over a hundred new and existing licenses and options.  But what if a new company’s budget cannot accommodate the fees?  What if the founders don’t want to share their equity?  What if a biotechnology startup didn’t need IP?  Eleven Biotherapeutics1, a new start-up from the stables of Flagship and Third Rock Ventures, is poised to take on biotherapeutic development in the absence of spawning, academic-licensed IP.

Intellectual property gives one the right to prevent others from operating in a particular technological space.  In the biotechnology sector, especially for smaller companies, a significant fraction of a company’s valuation is dependent upon their IP portfolio.  Companies often grow out of academic research with university-sponsored IP at their core.  But as much as this initial IP can support a new startup, it can also blind their research and development against ideas outside the protection already granted.  Eleven has already closed on a $35 million series A funding round from the two aforementioned firms without any IP to speak of.

This somewhat unique approach to a biotech start-up is fundamental to the ideals espoused by the Third Rock Ventures team2.  Their stated mission of founding “transforming” companies is supported by a tendency to build companies around powerful teams of thinkers and technologies in therapeutics areas. Constellation Pharmaceuticals is another Cambridge-based company in the Third Rock family that was founded with an understanding that IP will be obtained in the future rather than licensed from the beginning.  Constellation has taken a similar approach to therapeutic development in epigenetics as Eleven is poised to in biologics.

Eleven is approaching the biologics market with an open mind.  Without a foundational technology or IP portfolio, the company needs a way to generate value.  To do so, their central development focus will be on validated therapeutic targets with existing preclinical models and clinical benchmarks.  For example, rodent models for rheumatoid arthritis are well established3 and there are numerous biologics against various targets already in this space.  Those drugs all went through clinical trials in which reasonable end-points were established as hurdles for leaping past substantially improved alternatives.  With these reasonable, targeted approaches, Eleven hopes to quickly move through early research and development, resulting in clinical trials after just three years.  Cam Wheeler, Business Development and Operations Manager at Eleven and a PhD graduate of the Biological Engineering Department at MIT, suggests that efforts will be biased and that the clinical push will be focused on those compounds with the greatest market viability.  The success of their more fundamental research approaches should help support projects towards more novel targets and compounds in more diverse therapeutic areas.  Additionally, they will seek to acquire later stage lead drugs that complement their expanding pipeline.  The press release announcing their series A funding listed inflammatory conditions and coagulation disorders as two of the therapeutic areas Eleven will be working in.  Their website also references conditions resulting in muscle atrophy.

Precisely which targets within these areas they will be working on has been kept under wraps, but as Xconomy writer Luke Timmerman points out, there are hints in the specialties of the founders4.  Scientists Greg Verdine PhD (Harvard) and K. Dane Wittrup PhD (MIT) pioneer the types of protein engineering tools that will be put to use engineering the therapeutics.  The addition of Casey Weaver MD (UAB), K. Christopher Garcia PhD (Stanford), and even Reza Dana MD MPH MSc (Harvard) suggests a potential application area, given their overlapping interests.  Weaver’s research into T cell maturation and Garcia’s on immune protein structure/function relationships have both led them to studies of the Th17 CD4+ T cell lineage5,6.  Th17’s are a class of T helper cells that produce interleukin (IL) 17 and are implicated in autoimmune diseases such as multiple sclerosis.  Dr. Dana’s research on ocular transplantations and inflammation has also led him to T cell studies and the effects of Foxp3+ regulatory T cells (a competing differentiation fate for Th17 progenitor cells) in preventing transplant rejection.  It seems consistent with their stated therapeutic application areas that Eleven will be working towards some type of immuno-modulatory proteins related to Th17 differentiation or function.  Whether that means development of TGF-β or IL-6 variants to deter Th17 maturation or IL-17 antagonists to abrogate the production of other pro-inflammatory cytokines like TNF-α (the target for biotech blockbusters Remicade and Enbrel) remains to be seen.

Regardless of the specific therapeutic target, Eleven is poised to make a significant impact in the biotechnology community.  Most of today’s biotech companies are plagued by common canonical approaches and product pipelines resembling parched vines devoid of the once low-hanging fruit.  By poaching top scientific advisors and promising young researchers, like recent MIT graduate Mike Schmidt PhD, they are building an innovative team that should be able to push therapeutic development into uncharted territory.  Don’t be surprised if their type of innovation is richly rewarded.


References

  1. Eleven Biotherapeutics: http://elevenbio.com/
  2. Third Rock Ventures: http://www.thirdrockventures.com/
  3. Lindqvist AKB, Bockermann R, Johansson ACM, et al.  Mouse models for rheumatoid arthritis.  Trends in Genetics 18 (2002) S7-S13
  4. Timmerman L.  Eleven Biotherapeutics raises $35M, seeks to crank the amplifier up on protein drugs.  Xconomy (2/17/10) http://www.xconomy.com/boston/2010/02/17/eleven-biotherapeutics-raises-35m-seeks-to-crank-the-amplifer-up-on-protein-drugs/
  5. Lee YK, Mukasa R, Hatton RD, Weaver CT.  Developmental plasticity of Th17 and Treg cells.  Curr. Opin. Immunol. 21 (2009) 274-280
  6. Ely LK, Fischer S, Garcia KC.  Structural basis of receptor sharing by interleukin 17 cytokines.  Nature Immunology 10 (2009) 1245-1251
Christopher M. Pirie, PhD

About

Scientist & Co-founder, Manus Biosynthesis";s:15:"profile_teambio";s:432:"Dr. Pirie is a scientist and co-founder at Cambridge, MA based Manus Biosynthesis. Chris earned his PhD in Biological Engineering from MIT in 2011 where his thesis research was focused on therapeutic protein engineering and he was a recipient of the NSF Graduate Research Fellowship. Also while at MIT he served on the Institute Committee on Intellectual Property and served as a writer and editor for the Entrepreneurship Review.";s:11:"profile_bio";s:1019:"He received his Bachelors degree, cum laude with college honors, in Bioengineering from the University of Washington where he studied intracellular drug delivery. In addition to his academic research he has served as a student representative to the Institute Committee on Intellectual Property where he helps guide MIT policy on important IP issues like open source publishing and patent reform. While at Washington he served on the Bioengineering Curriculum Committee pushing for improved course work in molecular transport and mathematical modeling. Born in the San Francisco Bay Area, he grew up in Seattle and now lives in Cambridge. As a life sciences editor and writer for MITER he sources primarily research focused articles with tangential, intellectual excursions into ideas on venture capital and technology translation. Chris enjoys sailing the Charles River, reading classic literature and astrophysics books, traveling to places other people only read about, and BASE jumping off the Green Building.