D&MD:
As RiboTargets is a new company, could you start from the beginning and
give a run through of the company's progress to date?
NC: The company was founded in 1997 and was a spin-out from the
Medical Research Council's (MRC) Laboratory of Molecular Biology in
Cambridge (UK). The company at that time focused primarily on RNA and RNA
targets in the lead area of HIV. After a period of developing our research
there was a slight shift in emphasis to include work more broadly on anti-infectives,
including hepatitis C--again focusing on RNA.
The company developed a number of technology tools to form an
innovative drug discovery engine that enabled us to identify drugs
specifically to RNA targets. It was also apparent that our technology had
some major benefits in the structure-based design of drugs against protein
targets as well, so we evolved our strategy to the point where, today,
most of our R&D is on protein targets. This is a very important point
that I want to get across--that we're not just an RNA company. Our company
name suggests to many people that we are confined to RNA, or ribo,
targets, and that is not the case. We are a company that can target both
RNA and protein.
In a key piece of research that came from Venki Ramakrishnan's lab at
the MRC's Laboratory of Molecular Biology, the structure of the 30S
subunit of the bacterial ribosome was resolved. Through an exclusive
collaboration with Venki we focused some of our structure-based design
approaches to identify new classes of antibiotics that targeted the
bacterial ribosome. Then, in an important step last year, we grasped the
opportunity to apply our technology and expertise to the discovery of
novel cancer therapies. So the way we would describe ourselves today is
that we are a structure-based design company that develops novel cancer
therapies and antibacterials.
We've been through a series of rounds of financing. In July 1997, we
raised £7 million ($11 million). Then in July 2000, we raised £6 million
($9 million) through "blue-chip" investors. Apax was an early
lead investor, with the most recent round being led by J.P. Morgan in
September 2001 when we raised £32 million. This was one of the biggest
fundraisings in biotech last year. Given the whole business climate at
that time, we were very proud of our achievement.
D&MD: Having achieved that funding last September, what is
the future outlook in terms of funding? Are you now going for an IPO?
NC: That money was raised to fund our research activity and to
get drugs into development. Clearly, that's what the whole drug-discovery
business is about--to discover new drugs and get them through clinical
trials. Once we've got products in trials, then we're in a position of
strength. We have a number of really promising candidates that are in
discovery and that we should be able to take into clinical development.
On the specific question (about IPO), generally and not just in terms
of RiboTargets, a lot of people would argue that the market is definitely
closed for the foreseeable future, but that's something we would always
consider if the timing was right. As a management team, we would not only
have to consider if an IPO was right for RiboTargets, but also if it was
right at that moment. We believe that we have to be ready when the markets
open again. But that really is not the fundamental thing that drives us.
Driving us is actually drug development. We are in the business of
discovering new drugs and getting them through development. That's what
we're here for and we have enough cash to take us a long way forward.
It's important to get over to the industry that RiboTargets has a
drug-development focus--we're not a technology-platform company--although
ingrained in our whole approach is a strong drug discovery engine.
D&MD: In a sense the focus seemed to have shifted away from
an emphasis on developing antibacterials towards exploiting this
drug-discovery engine, because it seemed to be such a powerful way of
approaching drug discovery. Is this your view as well?
NC: We believe that our discovery engine is a powerful way to
discover drugs. We've developed a number of different technology
disciplines, which we've bolted together to provide an integrated
platform. We believe that this platform can accelerate the process of drug
discovery and improve the quality of leads discovered. We're progressing a
number of programs, which we believe will provide the evidence to validate
this claim. I don't want to hype up the situation, but we believe it is
better than what is currently available externally and we see it as a very
valuable asset. But the whole reason why we've invested in our discovery
engine is to generate products that will have a greater chance of
successfully passing through clinical trials. We need to try to beat those
great statistical hurdles--that, of 11 compounds that enter preclinical
development, only one gets to market. Everybody again will tell you
that--but we truly believe that we have ways to reduce those failure
rates. So, building value by using our discovery engine to get products
through to market quickly is key to our strategy. That's fundamental.
We will also in-license compounds to supplement our development program
and broaden our pipeline. There are a number of companies in the UK that
have taken the approach of saying: "Actually, we're going to be a
development-based company" and they've taken strategic decisions to
actually stop investing in research. We believe that it's important to
fuel our pipeline both through in-house research and in-licensing. That
way we spread our risk and build our value further.
In terms of the emphasis of the company now, it is really on our
quality targets: both our protein targets and the ribosome. We still have
some activity on hepatitis C but we've stopped our research activity on
HIV. It's not that we don't believe that the market is ripe for HIV, it's
just that we believe it's better for us to focus on our antibacterial and
cancer targets.
Our collaboration with the Institute of Cancer Research (ICR) is very
important for us. The ICR values the program that they have, and they
believe that RiboTargets has the necessary technology tools--the drug
discovery platform--to accelerate their programs. Hopefully, next year,
we'll start to see some results from that.
D&MD: Only five years after the foundation of the company,
you have a drugs pipeline. To what extent can you put a figure on the kind
of speeding up that RiboTargets can achieve? Would that really be of
interest to outside pharmaceutical companies because they might then come
to you?
NC: If you ask that question this time next year, I might be
able to give you a better answer. Clearly, I wouldn't want to make
unrealistic and unfounded claims at this time but we have encouraging
results from a number of our discovery programs and we hope to have data
available soon. If you actually look at the five years, in terms of what
we've been doing, in the last couple of years, we've built a very strong
foundation through our technology and are now preparing to enter
preclinical trials.
D&MD: To what extent are you actually developing X-ray
crystallography and NMR spectroscopy technologies--or are you simply
applying the latest instrumentation from other vendors?
NC: What typically happens in the process of drug discovery in
any company is that you start with target identification, then you go to
hit generation and lead validation, followed by lead optimization, and
then through to clinical trials.
We believe at the moment that there are a great number of targets that
have come out of the genomics revolution. So we're trying to focus our
efforts not on target identification per se, but to take some targets that
are known and to understand how to modulate these targets through our own
X-ray crystallography and NMR spectroscopy capabilities. Where we really
try to shrink the time of actually getting quality hits--it's not just a
matter of time but also of quality hits--is in the hit generation and lead
validation process. We're applying a whole bunch of technologies based on
structure-based design. We have our in silico screening technology,
rDock. That is computational software that is proprietary to RiboTargets
and is, in many instances, faster than other programs and with a greater
discrimination and power, in terms of its docking capabilities.
More importantly is that it is integrated into a holistic approach that
includes our other areas of expertise, among which is our cheminformatics
capability, rCat. This allows us to screen through around 3.4 million
compounds which are novel in a particular area.
Other areas of expertise that are also integral to the process, are
fragment screening and ligand-based design, which are based on
computational modeling. Other people are doing fragment screening, but our
development programs are showing some very interesting success in that
area.
Really, it's a combination of all these technologies that's allowing us
to generate results in the drug discovery process. To answer the original
question--"are we developing the techniques?"--in terms of our
structure-based design capabilities using X-ray crystallography, we have
Professor Rod Hubbard as Director of our structural sciences group and
part of our senior management team. Clearly his knowledge and experience
have been absolutely paramount in developing our capabilities. Being one
of the world leaders in this area, Rod's expertise in applying X-ray
crystallography to high-throughput 3D structure determination is advancing
the technique itself.
D&MD: You mentioned the rDock technology being proprietary.
Will you be prepared to license it to other people? Or will you just use
it yourselves?
NC: The way that we are using it at the moment, is that the
value of our technology is in generating our own molecules. We recognize
that our technology is accelerating the process of drug discovery, so
we're prepared to discuss with potential partners how we make it available
to them. We can sit down and discuss how to reduce their bottlenecks. The
proteomics and genomics companies have a whole number of different
targets. What we'd like to do is to actually see how we can collaborate
with them to discover new leads. That is something we're actively
pursuing. So, for example, a collaborator may say they're looking at three
or four targets that we could collaborate on. We would apply our
drug-discovery engine within traditional deal structures, by which we have
up-front payments, milestones, technology access, based on our
contribution to that program. We're talking to a number of people about
that.
What we're not willing to do is to just license the software, because
it's not just the software that makes the difference, its a totally
integrated process. However, it is very efficient software that has the
unique ability to be used against both RNA and protein targets, stemming
from a history in HCV and HIV.
D&MD: One of the collaborations that you had established was
with Johnson & Johnson. Is that exclusive, or are you talking to other
pharmaceutical companies?
NC: That collaboration is ongoing. It is on a particular site of
the ribosome. [Under the terms of the agreement, RiboTargets is to provide
the R.W. Johnson Pharmaceutical Research Institute (PRI), a Johnson &
Johnson company, with two unique targets associated with the bacterial
ribosome and novel compounds to interact with these two targets, and to
work with PRI to analyze these novel compounds to identify and optimize
potential drug candidates.]
The key focus of that collaboration now is on one particular site. That
is one area of development. It is not an exclusive deal on the whole
ribosome. We are talking to other major pharmaceutical companies in the
area of antibiotic research to see whether there are other opportunities
for collaborations. We are having discussions with them at the moment.
D&MD: Your Web site notes that the bacterial ribosome
contains many known and novel sites for antibiotic action, including that
for two of the four top-selling antibiotics, with combined sales of more
than $3 billion. So is there really room for more products in that area?
Wouldn't they just be knocking out the ones that had already been
established in the market?
NC: Well, there hasn't been a new antibiotic for about 15 years,
apart from Zyvox™ [from Pharmacia - Ed.]. The view is that all
the pharmaceutical companies have been trying to develop new antibiotics
from the ribosome. These are natural products in most instances and are
therefore more susceptible to the problem that's always dogged
antibiotics--the development of resistance.
The key difference is that now we know the structure of the ribosome we
can actually use some of the modern tools of structure-based design to
identify and rationally define new antibiotic classes which will eliminate
resistance. That's the key. If we can develop the right antibiotic for the
right target, then we could end up producing antibiotics with potential
sales of billions of dollars. It's not an easy task. The ribosome is a
complex structure. But we are actually best placed to succeed with the
technology that we have.
D&MD: Some of your products are in the lead optimization
phase. What sort of time scale are we looking at to get the first into
preclinical and then clinical development?
NC: We have very recently entered into an agreement with
Professor Colin Goodchild, Dr. Ray Nadeson, and Monash University,
Australia, to develop Alphadolone, a cancer pain product. The development
of Alphadolone marks a major transition for us, shifting the business from
a pure research base to become a research and development company. This is
very important as it will have a knock-on effect, spearheading the way
forward for other compounds to emerge from our internal pipeline.
D&MD: You're based near Cambridge, UK, at the moment. Do you
have any plans to go the US, in view of its importance as a market?
NC: We recognize the importance of the United States as a
single, homogenous market. It represents approximately 50% of world sales
of prescription drugs, is the fastest growing market at the moment and
clearly, it is vital to us.
For the immediate future, we haven't ruled out a base in the USA. But,
in terms of our operation in the UK, I think that it's likely to remain in
the Cambridge area. The other aspect is that we do have a research and
development unit in York--that is the base for our structural
crystallography.
