What will drugs look like in the coming decade? This is the
question being posed by Gregory Verdine and the next-generation therapeutic
modalities team he leads at Third Rock Ventures. One
answer, Verdine believes, is hybrid platforms of synthetically modified
biomolecules that combine the advantages of small molecules and biologics.
SciBX: Where do you see opportunities emerging
for new types
Gregory Verdine: I believe that 10
years from now, when we look at the types of molecular structures that we
consider to be 'drug-like', these structures will be considerably more diverse
than now. In other words, we are entering a period in which we will see a
significant expansion in the types of molecules that succeed as drugs. This
process is already underway, as many pharmaceutical companies have begun
explicit efforts at broadening the structural base of targeting molecules.
These new modalities are likely to include nucleic acids beyond antisense and
siRNA, carbohydrates and peptides, among others, but also interesting fusions,
such as small molecule-protein conjugates. Some of these classes of molecules
have a back-to-the-future aspect to them, for example peptides and natural
products, but recent scientific advances have suggested that they should be
looked at in a new light.
SciBX: How does Third Rock go about launching new
companies in such emerging areas?
GV: We recently launched a new company with Flagship
Ventures, Eleven Biotherapeutics Inc., with
the concept of bringing truly rational drug design to bear on the discovery and
development of next-generation protein therapeutics. This illustrates our
process. We brought together five founders that included myself; a biological
engineer, Dane Wittrup [Massachusetts
Institute of Technology]; a cytokine structural
biologist, Chris Garcia [Stanford
University]; an expert in Th17 [T helper type 17 cell]
cytokine biology, Casey Weaver [The
University of Alabama at Birmingham]; and a practicing
clinical ophthalmologist, Reza Dana [Massachusetts Eye and Ear Infirmary].
SciBX: Which potential new drug scaffolds are
attracting the most current commercial interest?
GV: The peptide area is particularly active,
and we are tracking this space very closely. There are a number of interesting
companies already developing modified peptides as new therapeutic platforms (see
"Companies developing new classes of peptide-based therapeutics").
Although peptides can readily be identified that selectively interact with a
target, the poor pharmacological properties
of unmodified peptides limits their usefulness as drugs.
SciBX: What are [some] recent academic
advances that could have an impact in peptide-based therapeutics?
GV: A very interesting area, although not quite
ready yet for commercialization, is the use of peptides as targeting
SciBX: What are [some] scientific advances
that would propel increased investment in peptide therapeutics?
GV: It's still early days in the resurgence of
peptide therapeutics, but the scientific breakthroughs that really command
attention are those that overcome some of the key obstacles of unmodified
peptide drugs-advances that could enable oral bioavailability, substantially
extend peptide half-life, protect peptides from proteolysis, enable active
cellular uptake or allow peptides to cross the blood brain barrier. To my
knowledge, no peptide platform developed to date combines all these features.
SciBX: What broad trends have you seen in
early venture funding?
GV: There is no question that most venture funds
have moved later to try to reduce the time that it takes to reach a value
inflection, the achievement of a milestone that increases the valuation of a
company. For these later stage investments, the value inflection is typically
tied to drug approval. Though this strategy was considered by some to be
conservative, in practice it has often proven quite risky because the costs of
late stage clinical testing, and the opportunities for failure, are high.
SciBX: Are there other sources of early
funding that are filling this gap in venture money?
GV: Pharma is
beginning to externalize more and more research, and this is a trend that is
very likely to continue. But it's not like the old days, where the money flowed
into the academic lab and the company sponsor hoped for results somewhere down
SciBX: In this challenging funding environment,
what do academics need to do to attract venture money?
GV: The biggest challenge is assembling a
package of data that gets a venture group excited about the opportunity and
where enough of the obvious risks have been removed that the VC
feels that the science is ready to go right now.
SciBX: Thank you very much for your time.
Kotz, J. SciBX 4(16); doi:10.1038/scibx.2011.445
Published online April 21, 2011
COMPANIES AND INSTITUTIONS MENTIONED
Aileron Therapeutics Inc., Cambridge, Mass.
Bicycle Therapeutics Ltd., Cambridge, U.K.
Constellation Pharmaceuticals Inc., Cambridge, Mass.
Dana-Farber Cancer Institute, Boston, Mass.
Eleven Biotherapeutics Inc., Cambridge, Mass.
Ventures, Cambridge, Mass.
Harvard University, Cambridge, Mass.
Eye and Ear Infirmary, Boston, Mass.
Massachusetts General Hospital, Boston, Mass.
Massachusetts Institute of Technology, Cambridge, Mass.
Laboratory of Molecular Biology, Cambridge U.K.
National Institutes of Health, Bethesda, Md.
PeptiDream Inc., Tokyo, Japan
Ra Pharmaceuticals Inc., Boston, Mass.
Stanford University, Stanford, Calif.
Rock Ventures, Boston, Mass.
The University of Alabama at Birmingham, Birmingham, Ala.
University of California, Santa Barbara, Calif.
The University of Queensland, Brisbane,
University of Tokyo, Tokyo, Japan
University of Texas Southwestern Medical Center at Dallas, Dallas, Texas