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| "This
is a great time to be a PhD in Biology in
India" |
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| Gauri Kamath |
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THIS year, Hyderabad-based Dr Reddy's Laboratories
(DRL) completed a decade of its drug discovery effort
- the search for a completely drug. Even today,
there isn't a single new drug from DRL, nor from
any other Indian company, in the market. After all,
drug discovery is a long, drawn-out process with
no guaranteed results. On an average, a drug takes
12 years to go from the lab to the market. If at
all it does. Yet, in its quest, DRL has tried interesting
experiments that other Indian companies might want
to follow. For instance, it has tried to leverage
scientific talent across continents. Four years
ago, it set up a research hotshop in Atlanta, US,
to focus on parts of the research process that the
Americans are good at. Since then, there has been
a transfer of skills from this setup back to India.
Uday Saxena, DRL's Atlanta-based chief scientific
officer, spoke to Gauri Kamath of Businessworld
on the promising new drugs in DRL's pipeline,
and how Hyderabad and Atlanta are working together
to bring breakthrough medicines to the market.
- What is the status of the new compound
for atherosclerosis (blocking of the arteries)
that has originated in the Atlanta lab?
The compound has just completed GLP toxicology
tests (safety studies in animals), which is
the final stage before entering human trials.
We are projecting that if everything goes well
then in January of 2005, we will take the compound
codenamed RUS3108 to human trials.
- Will this be the first in a new class of
drugs?
Inflammation, proliferation, and thrombosis
are the three major components of what causes
atherosclerosis. There is one company out there
that is looking to modulate inflammation - they
have an anti-inflammatory compound that is now
in phase 3 (the last phase of human trials prior
to marketing). I think our drug is first in
class because not only are we looking at inflammation,
but we've added on things like anti-proliferative
and anti-thrombotic properties also. In that
perspective, it may be first in class. In the
sense that around this target (an enzyme called
perlecan whose overexpression can mitigate these
three causes), there has not been any product
out there.
- You had identified a novel target for restenosis
(re-clogging of arteries after angioplasty)
some time back…
Actually, the 3108 programme was the restenosis
programme. When we started 3108, we thought
it will be very good for restenosis. But when
we moved forward, we realised that it has applications
for atherosclerosis also. Also in the restenosis
field, the standard of care was increasingly
becoming a device play i.e. drug-coated stents.
That as well as the fact that we thought 3108
would have applications for atherosclerosis,
which is a much, much bigger market; we actually
turned the programme into atherosclerosis. We
are still doing some studies to perhaps design
another compound in the same collection that
will be exclusively dedicated to restenosis.
- In 2001, you had tied up with US-based
Incyte Genomics to access their protein library.
How has that whole effort done?
Pretty good. We had actually extracted some
targets (genes and proteins that are associated
with disease) from that database, and some drug
discovery programmes have been set around those
targets.
- And these were specifically in which areas?
In metabolic disease areas like diabetes and
complications of diabetes.
- And have you started screening compounds
against those targets?
We had to do some additional validations because
the Incyte human genomics database tells you
the target's co-relation to disease but information
for it to be a druggable target requires additional
studies. The validation really entails this:
if you change the expression levels of the target,
for example, will it have an impact on the disease
or not? And that you can do either in cells
or in animals. After that we've set up screens
and we are in active screening mode right now.
Also, one of the benefits of the Incyte programme
is that internally, because of our experience
with them and the infrastructure and understanding,
we have now been able to institute a group dedicated
to looking at targets in Hyderabad. The genomics
and proteomics group will be responsible for
studying disease biology in different conditions
to see if we can get a handle on new targets.
This is a recent initiative that has happened
in the last one year. It is very exciting because
to be able to internalise this capability and
to be able to use it in our future discovery
effort is - from a scientific perspective -
a huge, a big step ahead for us.
- You found people easily to man these groups?
The way it is working is: a lot of these people
are molecular biologists - genomics is nothing
but molecular biology. It is the application
of molecular biology to certain genes and their
association with disease. We have an individual
in Atlanta who ran the Incyte programme for
us who is going to oversee all these activities
in Hyderabad. It will be a transfer of skills
from Atlanta to Hyderabad in this area.
- So he will move to Hyderabad?
Well, right now, he is travelling frequently
and eventually that might happen. But we have
PhDs in Hyderabad working on that and they are
reasonably independent. And able to work through
guidance being given by this individual.
- Where did you recruit them from?
A lot of them are from academia. Some of them
have done their PhDs in the US and some of them
have done it in India.
- Can you explain the biggest advantages
of working across continents?
In Atlanta, the skill set is to be able to take
a new target, do validation and do early discovery
biology and chemistry. Once it looks like a
development candidate, we turn it over to Hyderabad.
That whole model has played out very well. Let's
take RUS3108 as our role model. We think that
is the most advanced product of the collaboration
between Hyderabad and Atlanta. The original
target itself was conceived of in Atlanta. And
a lot of the validation and the early biology
and discovery chemistry were also done in Atlanta.
Then once it became clear that we might have
a development candidate on our hands, we turned
it over to Hyderabad and they did a lot of the
early development work. For example, probe toxicity
- where you make sure there is no toxicity related
to the compound - and additional efficacy profiling
was also done in animal models in Hyderabad.
They also designed the GLP toxicology test.
- So you leverage basically the biology skills
in the US?
It's not just the early target skills or the
early biology skills but also expertise in a
certain disease area. Some of the senior people
here have a lot of experience in the cardiovascular
area.
- Going back to the synergies between the
Indian and the US labs do you plan to move any
other activity around?
We are also looking to add our chemistry skills.
We have picked somebody from a large company
in the US, the co-inventor of a drug called
Celebrex (a Pfizer blockbuster for arthritis).
He is an accomplished world-class chemist. We
recruited him here in Atlanta and he is working
with groups of chemists in Hyderabad. In India,
what is practised is largely organic chemistry.
Slowly, we are beginning to understand medicinal
chemistry. There is a difference between the
two. Organic chemistry is when you can synthesise
a series of compounds. What happens in medicinal
chemistry is that you dialogue with the biology
data and say if I change the structure of the
drug here then maybe I can improve potency.
So there is a dialogue between biology and chemistry
in medicinal chemistry.
Another area of growth for us, and this has
not much to do with Atlanta, is we are aggressively
building our clinical development group. We
have recruited somebody from Bristol Myers-Squibb
who has gone back to India and is overseeing
that group now. We anticipate that our capability
to do clinical trials in India and globally
is something that will be moved very aggressively
in the next two to three years.
- Do you ever envisage a time when you would
be doing everything here and not in the US?
I don't know if they'll ever say that everything
will be transferred to India because the US
is perhaps the most advanced country as far
as medical research goes. The US culture is
to be inquisitive. There is money and also there're
entrepreneurs in the form of venture capitalists
or large pharma or biotech companies. They are
all looking at what's going on and they will
seize the opportunity if they see a new product
idea. And that's also fuelling all this outstanding
medical research that goes on in the US.
You are seeing these things real time. In fact,
I am going to listen to somebody who is coming
from Harvard to talk about Alzheimer's Disease.
This guy is an expert on Alzheimer's. Going
to one lecture and sitting for an hour, I am
going to absorb so much more than reading 20
pages on Alzheimer's. That's really learning
in real-time and that's really a competitive
advantage. So, I would believe that we would
have some presence in the US just to be able
to capture all this competitive intelligence
in real time.
- What are some of the other promising products
that Dr Reddy's is working on?
We have another programme that is completing
phase one of clinical trials in Canada. It is
our HDL (high-density lipoprotein or good cholesterol)
elevating compound - 10945. It is now being
shown that having low HDL is as bad as having
high LDL (low density lipoprotein or bad cholesterol)
or worse maybe. And although low HDL is a big
threat, and a big risk for atherosclerosis and
cardiovascular disease if you look at what's
available out there, you've got Niacin which
is not very effective and also has a side-effect
profile which is not desirable. And then you
have what's called the fibric acid derivatives
which are a little better than Niacin but usually
they cannot be combined with statins (that reduce
bad cholesterol) since they could cause a kind
of muscular dystrophy called rhabdomyolosis.
So what it means is that even though the unmet
medical need is huge there isn't a desirable
product out there. We believe 10945 will fit
in very nicely because it elevates HDL, it lowers
triglycerides but importantly it is not a fibric
acid-based compound. It is very different. It
might go better with statins than a typical
fibrate. It is very exciting in that respect.
We are not the only ones, there are other companies
working but we are pretty excited that this
compound will be very useful in the management
of low HDL and high triglycerides.
- How far away is a compound from commercialisation?
Actually 10945 came exclusively from Dr Reddy's
in Hyderabad. That has pretty much completed
phase one. Now there are plans to move it to
phase two. That is our most advanced internal
programme. It has clear attributes of a winner
in differentiating from what's out there, so
its very exciting. The second one is 3108 which
originated from Atlanta. That is going to enter
phase one next year if everything goes well.
- Do you see a time when a lot of the research
and development activity is outsourced by global
companies to India?
That won't happen until people here are comfortable
that the new patent laws are adhered to. I think
there will be a wait and watch period. I think
the less intellectual property-based work like
clinical trials will be outsourced first. I
can see that happening already. But the more
intense, intellectually property-driven work
like finding a new target, new compound and
all of that, I think people will wait and watch
because that is their whole business. That is
what this is about - protecting your secrets
through intellectual property rights (IPR).
Until that is executed well in India, I don't
see people rushing to do that in India.
- What is the likelihood that they will own
their setups here?
Even in the past there were companies like (German
major) Hoechst that had big R&D centers
here. But if you talked to people there they
would always say that the best stuff was always
done in headquarters. Or after a certain while
the project was taken away from there. In those
days it was done because IPR protection was
a big issue. In the future they might buy out
some of the existing labs and use the infrastructure
rather than start a whole new thing. We have
some pretty good labs in India.Once they are
comfortable that this is where we could be in
the long run they might actually make some moves.
I think some very exciting times are ahead for
pharma whichever way you look at it. As a PhD
I never imagined the kind of opportunities I
would have. My opportunities were either to
go into a CSIR (government) lab or a a university.
Now there's a whole new very attractive pharma
and biotech industry that is rapidly moving.
So the growth potential both financially and
professionally is huge in India. So I think
this is a great time to be a PhD in biology
in India, there has never been a better time
I think.
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