Fintan Walton:

Hello and welcome to pharmaventures business review here at Bio in San Diego California. On this show I have Khursheed Anwer who is chief scientific officer and senior vice president at the company called EGEN which was formerly called Expression Genetics. Welcome to the show.

Khursheed Anwer:

Thank you Fintan Walton good to be here.

Fintan Walton:

Good. Khursheed AnwerEGEN is an interesting company because it is developing these new platforms which all revolve around some interesting technology that's coming up to the pharmaceutical industry that technology is one that people are now familiar with which is interference RNA, siRNA, shRNA and so forth. Tell us about the origins of Expression Genetics and how you got involved in this new exciting area.

Khursheed Anwer:

Very good. Expression Genetics was founded in University of Utah by professor Sung Wan Kim's laboratory and then it was fully operational in July 2002 in University of Alabama and that's when I joined the company and before that I was working with another company Valentis, GeneMedicine which had history of developing DNA therapeutics for quite some time and so I moved to University of Alabama started this company R&D from scratch. Hired very good people locally and then from nationally to really tackle this problem of Nucleic acid therapeutics. Now as you said nucleic acid therapeutics is a powerful tool to treat diseases. You can have a over expression of a good gene that can fight cancer, lower blood glucose level through gene therapy approach. You can also do opposite to it. You can inhibit the expression of a bad gene such as a cancer causing gene, a gene that's belong to virus and cause infection by a very opposite approach which is to inhibit the expression of those proteins and that's as you said gene silencing. So it's a very cutting edge technology. There is no doubt there's no doubt that nucleic acid is going to be a powerful therapeutics but the question is that how you get to the site of their action. For example if it's a DNA therapeutic it has to be at the nucleus where it works as a transcription factors and produce protein. If it is siRNA it has to be inside the cell so from the side of injection to where these therapeutics perform key is delivery and that's only the core of business of Expression Genetics.

Fintan Walton:

Sure

Khursheed Anwer:

And I think my experience in nucleic acid Delivery and of my colleagues and the management Danny Lewis was been involved in control release for long time, Milton Harris who has developed PEGylation technology, Dr Robert Langer from (indiscernable) are the senior type of management people on the board that has really supported our effort into research and development. I think we are at a very great stage to be able to take this delivery technology into new class of therapeutics which are DNA and RNA .

Fintan Walton:

So Khursheed Anwer what's really important here you've described how your company is positioned in this whole area of nucleic acid therapeutics. Now clearly as you've just identified there are big issues and big hurdles the companies go through now you have developed two different platform technology platforms could you tell us a little about the first one which is the TheraSilence-technology and why it is positioned and what it differentiates itself from other approaches.

Khursheed Anwer:

Very good. Certainly delivery as I said matters in terms of therapeuticTheraSilence platform taking this siRNA into the cell for performing the gene inhibition. Our approach is unique in the sense that we use a flexible chemistry which allows us to incorporate different elements into our delivery system that is required for safety and high efficiency unlike inflexible sort of delivery system have tried in the past so this gives us the flexible chemistry to be able to put elements that you need for efficient delivery.

Fintan Walton:

Yeah

Khursheed Anwer:

And I think that's a very important point in terms of our success that we have seen with DNA delivery so far and we hope to extend that experience and functionalize delivery system into siRNA and I want to point out to you that delivery is strictly very key factor but also success would be the selection of therapeutic target, delivery modality and the disease indication. Often time business department may come up with a huge billion dollar therapeutic area and then enforces your technology to achieve those business goals. Our approach is very different. We look at our technology where it is applicable. So the choice of therapeutic target, delivery modality and cancer indication has to be compatible with the delivery technology and that's only the best scientists determine what system is going to work for what indication and that becomes our business goal. So that's very important point.

Fintan Walton:

But that that is a very important point because it means that you have multiple competences basically in the end, so how do you get those multiple competences?

Khursheed Anwer:

Excellent point. We have this integrated performance model here. We have this biologists, formulation scientists and chemists working together. We have organic synthesis chemist and they are able to, their capability to synthesize this novel chemistries as I talked to you about flexible chemistry so it is very important that chemists and biologists and formulation scientists work together. There has to be a feedback because yes it's a delivery issue but there is a lot of biology involved in it. You have to understand how the DNA or RNA is taken up and for that interaction is critical and that's how we have a skill sets of people scientists who have capability in chemistry and other disciplines and we have hired those people assembled a team of people I think I really commend my scientists who on a daily basis have a this communication between different disciplines and it is just lot of fun you are now learning science.

Fintan Walton:

Good and now the other technology it's the TheraPlas-technology could you tell us about that is that taking another different approach?

Khursheed Anwer:

Yes. Now TheraPlas-technology is based essentially a gene therapy technology. As you know gene therapy technology is being around for quite some time and our approach in TheraPlas is to take a plasmic DNA and deliver with a functionalized type of delivery system. Again same approach take a small say polymer and then build around it chemically attributes that take DNA into the cell as opposed to siRNA and in this case DNA goes all the way to the nucleus an extra mile an extra step it has to go as compared to siRNA.

Fintan Walton:

Sure.

Khursheed Anwer:

Now we have about 15 years of experience in delivering nucleic acids through some prior previous employment that I have Gene medicine, Valentis. so all that experience what works what does not work became very handy. So what we have been able to do create a functionalized delivery system based on flexible chemistry that allows us to give local concentration of a therapeutic molecule and in this case our lead product is a Lipo polymer that carries Interleukin12.

Fintan Walton:

Okay.

Khursheed Anwer:

Locally at the site of tumor and Interleukin12 is a very important Anti cancer molecule. It has acted

Fintan Walton:

So where did you get IL12 from?

Khursheed Anwer:

Yeah the IL12 is licensed from Wistar Institute.

Fintan Walton:

okay, okay.

Khursheed Anwer:

And our part is the Lipo polymer delivery system so our IP position is on the composition of the polymer, composition of the plasmid and the polymer in application for cancer.

Fintan Walton:

So where is this product now? It is in phase 2 phase 1 clinical trials at present?

Khursheed Anwer:

Yeah we have done one phase 1 mono therapy trial couple of years ago successfully completed that in advanced stage ovarian cancer patients these were stage 3 and 4 where chemo resistant nothing has worked, these patients were basically told to go you know on and pray that kind of patient population and we have found in a dose escalation study in that patient population to get a dose dependant efficacy response very (indiscernable) data. You almost you unexpect something like this from a phase1 cancer trial so that's very encouraging and what we did we had to make a business decision should we move on with mono therapy to phase 2 trial. But if you go as a mono therapy it will be second third or fourth line of sort of therapy so we thought will our or strategy will be to combine with a standard of care such as chemo therapy and hence you can get a large patient population. So being with that model business model we started a combination trial last year in summer where we are combining IL12 polymer, you know our EGEN001Theroplas candidate with chemo therapy Docetaxel and Carboplatin and so far you know we have treated nine patients with dose escalation, no you know serious systemic toxicity. The only minor complaints are abdominal pain, low grade fever which subsides after 24 hours. So this product is now ready for going into say further stage of development. We have orphan drug status for this product.

Fintan Walton:

Was gonna ask you a question here.

Khursheed Anwer:

Exactly an orphan grant from FDA that suggests you know that encourages to go forward. Right now we are looking for a partner to take this product into a pivotal clinical trial either phase 2 or phase 3 trial.

Fintan Walton:

This is still targeting ovarian cancer is it?

Khursheed Anwer:

This is still targeting ovarian cancer and but we do have a proof of concept of this product in a multiple cancer indication animal models. So we are also talking to FDA in going at the second indication. So in terms of business model we ourself will take it to next trial if we sure up some funding for it or get a partner to do it and also apply this product for additional cancer indication either ourself or through some partners.

Fintan Walton:

Okay so you are looking for a partner to take it after phase 1 or you are gonna complete phase 1 trials yourselves?

Khursheed Anwer:

Yeah this phase 1A for a combination trial that ongoing ovarian will finish that by next year this time and so we hope that partner will pick up from that point on.

Fintan Walton:

Okay.

Khursheed Anwer:

We may get accelerated development because of orphan status and there is this debate whether we can go to the phase 3 trial of course FDA has to kind of approve that plan so we would like the partner to pick up from after the completion of phase 1A trial.

Fintan Walton:

Right so what is the corporate strategy then taking you starting out as a platform technology company clearly you've now got a product that is therapeutic going into clinic or in clinic clinical trials right now, so what is the what's the strategy for your company going forward?

Khursheed Anwer:

See we are research and development company and we will stay that way.

Fintan Walton:

Okay.

Khursheed Anwer:

So our strategy would be take a product to phase 1 or phase 2 and get a partner to go forward for marketing and critical clinical trial that's for TheraPlas but TheraSilence it's still early stage in pre clinical so we will welcome any partner who can pick up at pre clinical stage and do a phase 1 and beyond but ourself also will take a TheraSilence into a phase1 study. So the model is phase1/phase2 not beyond that by ourself.

Fintan Walton:

But it looks like TheraPlas is the one that's most likely to be the one that's going to generate products going into future

Khursheed Anwer:

Yes.

Fintan Walton:

In the short term.

Khursheed Anwer:

Its closer to you know getting into the, you know further clinical testing absolutely.

Fintan Walton:

Right and so what's gonna what we gonna look at for now in the next 12 months from EGEN?

Khursheed Anwer:

Within next 12 months we would like to complete this ongoing combination trial. We would like to atleast expand this into an additional indication. We would like to continue with our siRNA in a platform, get proof of concept, move into preclinical development and also we would like to get our Series B funding completed that's on going right now. We need about $20 million we got you know 75% of that money in our bank we are still looking for the difference. So next 12 months strategy is to move phase 1A product into you know next stage through some partner, new indication by ourself and some additional funding for us to continue our research and development.

Fintan Walton:

Well Khursheed Anwer we are looking very much to seeing that development over the next 12 months and many thanks for coming on the show.

Khursheed Anwer:

Thank you very much appreciate that.

CSO and Senior Vice President