Idera Pharmaceuticals and Toll-like receptors




Episode Loading...




PharmaTelevision requires Javascript enabled and Adobe Flash Player to watch our programmes. If you do not have Flash installed, you can download it for free from the Adobe Flash homepage.

Improve your Internet experience and start watching exciting new video content.

Video title: Idera Pharmaceuticals and Toll-like receptors
Released on: March 24, 2009. © PharmaVentures Ltd
Share/save this page:
Email
Bookmark
Facebook
Twitter
LinkedIn
Follow us:
RSS
Twitter
  • Summary
  • Transcript
  • Participants
  • Company
Dr. Sudhir Agrawal founded Idera Pharmaceuticals using the science that he studied as part of his post-doctoral research. Now this in depth understanding of the company’s core technology has enabled him to take the role of both CEO and CSO. Here he describes the significance of Toll-like Receptors and their application in the immune therapies covering all aspects of their effect and their unique functions.
Foundation of Idera Pharmaceuticals and it's technology focus
Fintan Walton:
Hello and welcome to PharmaVentures business review here in San Francisco. On this show I have Sudhir Agrawal, who is CEO of Idera Pharmaceuticals which is based in Cambridge, Massachusetts. Welcome to the show.
Sudhir Agrawal:
Thank you very much.
Fintan Walton:
Sudhir, you're the founder of the company back in 1990 that's 18-years ago. I am sure you've had a journey in that time. Tell us a little bit about the foundation of the company, it's originating technology focus and where you are today?
Sudhir Agrawal:
Sure. Thank you very much. So we started out in 1990 based on principal of Antisense technology in which we create a synthetic piece of DNA and the concept was that with the Antisense piece we can shut down any gene. It became very popular as an Antisense technology and as we progressed this technology into clinical evaluations we observed that host was responding to these DNA pieces as foreign invaders.
Fintan Walton:
Right.
Sudhir Agrawal:
And created an immune response, which then let us to transform the company into what we do today is modulating the immune response through Toll-like-receptors.
Fintan Walton:
Right.
Sudhir Agrawal:
And the company was founded by Paul Zamecnik who is now 96-year old individual, still remains very active. Has been decorated with Lasker prize as well as with National Medal of Science. That is very fortunate we are working with him.
Functions of Toll like receptors and their significance in potential therapies in diseases.
Fintan Walton:
Right, so clearly you shifted to Toll-like-receptors. Tell us about the function of those receptors, because that's the basis to your company now and their significance in disease.
Sudhir Agrawal:
Sure, Toll-like-receptors are defense in new receptors in our body. To-date 11 Toll-like-receptorshave been identified. Their function is to defend us against invading pathogensand bacteria and virusesand depending on each Tolllikereceptor they have a defined function based on that they are expressed in different cells, in different places. Some Toll-like-receptors lead to just a protection which is a immediate defense. In some cases they will lead to a memory [ph] responses which would be down the road protection against with the same pathogens. So they are " they are really part of a natural immune defensive Receptors.
Fintan Walton:
So what is their significance in relation to potential therapies for diseases?
Sudhir Agrawal:
So what we are trying to do is create synthetic pieces of DNA or RNA so that why they will be mimicked as for the body as pieces of DNA or RNA coming from the invading pathogens.
Fintan Walton:
Okay.
Sudhir Agrawal:
And that will create an immune response. So our purpose is to trigger the immune response which is well orchestrated and well controlled which is a natural process. And once that immune system is activated this could potential be useful for a broad range of diseases including asthmaand allergiesfor cancer treatment for use of these compounds as vaccine adjuvant and also for infectious diseases.
Fintan Walton:
So, is it prevalent to sort of hyperimmune response operating a hyperimmune response or that's completely different to that?
Sudhir Agrawal:
No this is the receptor mediated, so we are engaging a receptor which body engages to defend us against for invading pathogens. So our compounds wind to these receptors and really we use the same system so it's well or orchestrated so we are not hyper activating it. We are not under controlling it, is really well controlled immune system.
Identification and selection of compounds.
Fintan Walton:
Right, so then you mentioned a number of the potential applications. How did you select and identify the " you've got three compounds in clinical development. How do you select and identify those compounds?.
Sudhir Agrawal:
So we go through a very extensive discovery process in which we design the compounds and that's through Chemistry, then we test them and various as the systems including human blood cells so that we know the compounds are working. Then we profile them and so each compound even though it may had wind to the same receptor because of the Chemistry it is different. So then we profile them and see which type of immune response is triggered and based on that then we can make a judgment what would potential be useful for which disease applications. So we have three compounds in clinic. They all are three different profiles for three different indications.
Types of Toll like receptors and their competences.
Fintan Walton:
You mentioned that there are different types ofToll-like-receptors and I think there are 11?
Sudhir Agrawal:
That's right.
Fintan Walton:
Isotypes types or equivalence. So there each of those respond to the same " same molecule or there is a differential response?
Sudhir Agrawal:
No, that's a very good question. They all are unique in function, so if we talk aboutTLR4 this would be on the cell surface and it would respond to only LPS Lipopolysaccharides our objective is to really what with receptors which are inside the cell at TLR7, TLR8and TLR9 and these are the receptors was recognized pieces of DNA and pieces of RNA specifically not no other compounds will really recognized by them.
Fintan Walton:
Right, so what differentiates you from other "other companies in the same field?
Sudhir Agrawal:
I think the chemistry. My background is in the chemistry after graduate and doing like post-doctoral in Cambridge at Molecular biology Lab in Cambridge and that was in Chemistry. And so that has been the basis for our working the Antisense -- and that let us to go intoTolllikereceptor compounds as well industrial chemistry. So that way we can fine tune the structure and increases the probability of success.
Fintan Walton:
Right, but then against that you've certainly you are in a number of different therapeutic fields and you move from chemistry to biology and so forth. So how did you build that competence?
Sudhir Agrawal:
So the idea was that once we identified compounds then now they are very broadly actually capable for broad range of diseases in a small biotech company really can't put the resources behind.
Fintan Walton:
Sure.
Sudhir Agrawal:
So the application was the advantage we have was the compounds are available, could we advance them in parallel for multiple indications. So we took a different business strategy that were we started to interact with number of pharma companies through research collaborations and which ended up into a business relationships. And so we are working now with three different pharma partners, with three different indications, while we continue to advance our own programs in infectious disease and in the autoimmune diseases.
Partnership payments and company's cash resource.
Fintan Walton:
And you talked there about developing the relationship with these pharmaceutical companies clearly that means obviously that you what originally did they just did some small studies with you to see what whether those molecules work in their particular models, or how do that " how to those relationships come about and how do they develop?
Sudhir Agrawal:
Sure, actually again it's to start from a you know very early stages which is exchanging the compound and allowing them to what with the compounds so that they generate data and believe in the same scientific principle as we have because we are working on that very numerous scientific principles. And that leads us to develop a confidence. And that gives us the confidence and that really results into our partnerships. So all three partnerships we have are based on the data generated to the prior to entering the partnerships.
Fintan Walton:
That's another journey in itself I'm sure having that experience. The strategy that you took in terms of partnering brought in cash to understand, how much cash is that partnering brought in?
Sudhir Agrawal:
So between the three partners we have received over 75 million in last 4-years which is in form of upfront payments and milestone payment.
Fintan Walton:
Okay.
Sudhir Agrawal:
And as these programs continue to go forward at different stages we could potential receive up 900 million in potential milestone payments. And once these compounds are commercialized then we are going to see royalty strong three partners.
Fintan Walton:
Right, key thing obviously for any public reported biotech company and even private company is the amount of cash you have, so as of today how much cash do you actually have?
Sudhir Agrawal:
At the end of third quarter 08 we've announced that we had about 60 million cash in the bank. But if you look back from those four, five-years we've been spending on there 14, 17 million. And so we have been very prudent produce of cash certainly this cash has been supplemented with the milestone payments coming from three partnerships. So we are really in a very fortunately place with the economic times and that we have a cash for continue to execute our programs.
Focus on chemistry of compounds and the deals with Merck, Merck KGaA and Novartis.
Fintan Walton:
You mentioned you got three different partnerships, from a strategic point of view has that been a good thing. I mean obviously there are three different indications or three different therapeutic areas that you're " issues those partnerships focus on, but in the sense although you are spreading a bets across number of partners, in the way are you spreading yourself too much and are you not too exposed to the danger of just being spread rather than focus more on company?
Sudhir Agrawal:
Now we are very much focus in the chemistry of compounds at Idera. What we are looking for is how to advance different therapeutic indications, and that requires different expertise. So when you work with Novartis [PharmaDeals ID = 20566] on asthma, allergy indications they bring the expertise to develop it. Our involvement is they are but so the expertise they bring on the table is very important , same thing is what the Merck and company on vaccine applications. And Merck [PharmaDeals ID = 25979]is a leader there global leader to vaccine development, so they bring that expertise to the table. And same thing for Merck KGaA [PharmaDeals ID = 29310]they've been very, very good in developing new biological therapies, so we are very glad to be working with them.
Fintan Walton:
So you are going to where the experts are well then -?
Sudhir Agrawal:
I think that increases the probability of success, but it also in economic times bring the financial resources while we continue to expand upon the discovery platform like Idera we have our programs in infectious diseases for hepatitis C . And we are working now in a very broad application which is autoimmune diseases.
Fintan Walton:
Right, and that was the basis of the press release recently?
Sudhir Agrawal:
That's right. So we've, last week announced that we published a new class of compounds which block immune activation through Toll-like-receptors certainly Toll-like-receptors play a role which is a invade you know working with these invaders, but under autoimmune diseases environment were the immune system is compromised and there is not a self tolerance is broking [ph] in that conditions the autoimmune diseases could be fixed like blocking Toll-like-receptors. So these new class of agents would be able to block that.
Fintan Walton:
So in the case of use of these molecules in autoimmune is that use for blocking autoimmune progression or well they will be used prophylactic in?
Sudhir Agrawal:
We have studied both ways, in animal models when we look at for say a example for Lupus Arthritis or multiple sclerosis or Psoriasis these are selected autoimmune diseases in both cases we have looked there prophylactic as well as our treatment models. So when we are looking for clinical developments certainly we will keeping that in mind, but as we go forward first thing to show would be " could be stopped the progression of that disease and then may be take a step back once the compound is safe and effective to look at if it could be useful for prophylactic senses.
Future going forward with Toll like receptors platfom.
Fintan Walton:
Okay, so what is the strategy now going forward for Idera?
Sudhir Agrawal:
I think for our strategies there one is the short-term and then mid-term and then long-term. Long-term certainly we want to be a full fledged pharmaceutical player, but in short-term is to convert the scientific useful into proof of concept in clinic and that's through multiple indications. And then see where the probabilities hide and then expand that into we looking for a mid-term strategy to really taking to the late stage trials to show that safety and effectiveness is compiling enough to market it.
Fintan Walton:
I see you are confident that Toll-like-receptors power is suitable basis suitable platform for future therapies?
Sudhir Agrawal:
Well we use them in our own body for infection, so when you get infections and you can feel tired and muscle ache and flu like symptoms and sneezing and that's means the Toll-like-receptors have been engaged by these invading pathogens and which is really creating an environment to defend it. And our principles are the same. So once we agree the compounds we are engaging the same receptors, so we hope to have a outcome which is positive.
Fintan Walton:
So that " it's focus will continue to be on, on those particular sectors?
Sudhir Agrawal:
That's right. So we are focused on Toll-like-receptors.
Fintan Walton:
Right, and you are not tempted to move into other " other technologies or any therapeutic areas that use different molecules or different basis of disease?
Sudhir Agrawal:
Certainly we, as I said we started out as an Antisense company. And that remains to very close to my heart as a technology in science and since now we now how to avoid immune activation through a fall in DNA which is an Antisense certainly we are exploring now and perfecting Antisense. So it could be Antisense for Toll-like-receptors, so that we can modulate them through use of Antisense but for many other indications as well.
Fintan Walton:
Okay. Sudhir, thank you very much indeed for coming on the show. Thank you.
Sudhir Agrawal:
It's my pleasure. Thank you.
Sudhir Agrawal
CEO&CFO
About Sudhir Agrawal, CEO and CSO Idera Pharmaceuticals. Since joining the Idera Pharmaceuticals. in 1990, Dr. Agrawal has served in various capacities including Vice President of Discovery, Senior Vice President of Discovery, and Acting Chief Executive Officer. He was appointed Chief Scientific Officer in January 1993, President in February 2000, and Chief Executive Officer in August 2004. Dr. Agrawal has led the Company's transition into the discovery and development of targeted immune therapy based on Toll like receptors. Dr. Agrawal received his D. Phil. in Chemistry in 1980 and carried out his post-doctoral research at the Medical Research Council's Laboratory of Molecular Biology in Cambridge, U.K. While working at Worcester Foundation of Experimental Biology, he carried out work in Antisense technology with Paul Zamecnik, MD, and based on this technology, the Company was founded. Dr. Agrawal has published over 275 research papers/reviews and has edited two volumes on oligonucleotide chemistry and one on Antisense therapeutics. He has also authored over 300 patents, issued or pending worldwide. He is a member of the editorial board of Oligonucleotides, Trends in Molecular Medicine, IDrugs, and Human Vaccines.
Idera Pharmaceuticals
Idera Pharmaceuticals (Idera) is a biotechnology company engaged in the discovery and development of synthetic deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) -based drug candidates targeted to Toll-like-receptors(TLRs), to treat infectious diseases , autoimmune diseases , cancer, and asthma and allergies, and for use as vaccine adjuvants. As a small- to mid-cap public company, it has slowly but surely been proving itself as a leader in theTolllikereceptor (TLR) space, and has the ample cash and multiple Big Parma partnerships to prove it's worth in an otherwise down market. Additionally, Idera benefits from an extensive patent position, much of it as a result of Dr Agrawal's efforts. The Company is collaborating with three pharmaceutical companies to advance it's TLR-targeted compounds in multiple disease areas. It is collaborating with Merck KGaA for cancertreatment excluding cancer vaccines, with Merck & Co., Inc.Merck & Co for vaccine adjuvants and with Novartis International Pharmaceutical Ltd.Novartis for treatment of asthma and allergies. Merck KGaAand Merck & Co are not related. In December 2007, Idera entered into a licensing and collaboration agreement with Merck KGaA for the research, development and commercialization of it's TLR9agonists for the treatment of cancer , excluding cancer vaccines. Under the agreement, the Company exclusively licensed it's clinical stage drug candidates IMO-2055 andIMO-2125, as well as other TLR9agonists, for the treatment of cancer, excluding cancer vaccines. Idera and Merck KGaA are evaluating IMO-2055 in clinical trials in cancer patients.