Andrew Bray discusses how Broadvector focus on conditions of the ageing population




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Video title: Andrew Bray discusses how Broadvector focus on conditions of the ageing population
Released on: December 13, 2010. © PharmaTelevision Ltd
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In this episode of PharmaTelevision News Review, Fintan Walton talks to Dr Andrew Bray, CEO of BroadVector.
Origin of BroadVector
Fintan Walton:
Hello and welcome to PharmaTelevision News Review here at AusBiotech in Melbourne in October 2010. On this show I have Andrew M. Bray, who is CEO of a company called BroadVector which is based here in Melbourne, welcome to the show.
Andrew Bray:
Thank you Fintan Walton.
Fintan Walton:
Tell us about BroadVector, because it's a recently emerged company it's come out of a several companies which have now merged, just tell us little bit about that history?
Andrew Bray:
Yes, okay that's great, what we have is well first our BroadVector is a company that's focused on diseases of the ageing population, so it's quite an intentionally set of targets that we've looked at. The two therapies that we are concerned with sort of prostate cancer early stage prostate cancer and another condition that also flicks all the people is Aseptic Loosening of Prosthetic hips.
Technology and areas of focus
Fintan Walton:
Right, now behind every good therapeutic focus there is an underlying technology, so tell us little bit about what the underlying technology feature is areas of focus?
Andrew Bray:
Okay, the technology for these two programs actual come from different sources but they are very similar, so the prostate cancer therapy technology comes from the CSIRO it was developed by Dr Gerald Both, who is now our Chief Scientist with BroadVector and essentially that's a technology that's concerned with introducing a gene into the target tissue in this case prostate with cancerous prostate, the gene encodes an enzyme which will convert a prodrug into an active drug in the target tissue itself, so in other words regenerating an active compound directly in that tissue that's requires the treatment. In the case of the Aseptic Loosening the technology is actually come out of Europe, it's come out of the UK and Netherlands, but it's the same sort of technology in that vector of a modified virus which is nonreplicating carries in a gene which once again encodes an enzyme which converts a prodrug into an active drug in that target tissue in this case the target tissue is this loosening tissue that's connected with Aseptic Loosening, and I'll go to that in a bit more detail.
Prodrug :Functions and applications in prostate cancer area
Fintan Walton:
Right, well just lets go back to the prostate cancer first of all, tell us little bit more about the prodrug and how that was discovered and how you see that been applied specifically prostate cancer?
Andrew Bray:
Sure, the enzyme that's encoded is an E. coli PNP enzyme and that was first researched actually in United States and that's controlled by a company called PNP Therapeutics that's in Alabama, (Birmingham, Alabama) and essentially that's that so the research in some of the techniques CSIRO is focused on making use of that gene in a therapeutic sense and so essentially what happens there is a vector this particular vector happens to be a non-human adenovirus it doesn't replicate in humans so it's acting purely as a container to carry the gene if u like. The gene is under the control of a prostate specific promoter and that's also a technology that was developed jointly by CSIRO and Sloan Kettering Institute, now that intellectual property also comes to us and will be assigned to us as well. The gene converts, essentially what it does the prodrug is a fludarabine, so fludarabine is a nuclear side it's an off-patent anti-leukemia drug it's been used in clinics all over the world for many, many years.
Fintan Walton:
Yes, so it's established drug?
Andrew Bray:
Yes its safety profile is very well understood. So in this particular case we are not using it in the same way that have been used to treat leukemia so you don't have repeated uses it's essentially a short-course of treatment with that prodrug or of course it's a drugging leukemia but normally wouldn't have any impact on prostate cancer, but it's converted into 2-fluoroadenine when it comes in contact with the enzyme, so interestingly the E. coli PNP enzyme causes this conversation but mammalian PNP enzyme does not so hence this selectivity.
Fintan Walton:
Alright, okay. So there you've got a drug that's already recognized lets say it's been through the regulatory process?
Andrew Bray:
Widely uses.
Fintan Walton:
and now you are returning it from a function which has a prodrug function into an active drug that's now going to be specific for prostate cancer?
Andrew Bray:
That's right and the specificity comes from the fact the gene is turned on essentially in the prostate, the 2-fluoroadenine itself Fintan is inhibits DNA and RNA synthesis in the cells and the prostate, so it's selectivity is not for cancer it's the selectivity is for prostate tissue and so what happens is 2-fluoroadenine is a small molecule compound a cell which contains which is producing the enzyme when the prodrug is taken up will be converted it into the 2fluoroadenine that will basically cause apoptosis of that cell, but it also spread out into neighboring cells and also cause these surrounding cells to also die. So it's not necessary to have the vector into every cell of the prostate to have a therapeutic effect however it will only turn on in prostate tissue.
Fintan Walton:
And just remind us where that is in the clinical development?
Andrew Bray:
That the clinical stage of this it's been approved by the Australian regulated the TGA for a Phase I clinical trial at a major hospital in Sydney, so it's we have all the regulatory approvals in place all the preclinical has been completed, so this will be first time in man for this drug and the clinical trial is an 18 patient trial which would be at St Vincents Hospital in Sydney and that's happens to be the largest prostate cancer clinic in Australia.
Hip replacements Prosthetic implants therapy program: Purpose and benefits
Fintan Walton:
Okay, lets go to the second program now, because it's for lottery for hip replacements prosthetic implants tell us a little bit about that now, because I guess you said it's the same principle you've got a prodrug?
Andrew Bray:
Yes this is a really interesting program and we came across this of course looking at a number of projects and we saw, we came across this really interesting application to destroy a non-cancerous tissue using a very similar technology to the prostate cancer program, now in this particular case the enzymes in this case is a as a E.coli nitroreductase the prodrug is anNitroaryl(indiscernable) so small molecule compound once again, it's unlike the first program this is not a widely used drug at all this would be new drug compound, but once again this is interesting because we found when we looked into it that there is lot of people who suffer from this condition called Aseptic loosening, so essentially what happens is you may be aware that the number of hip implants worldwide is growing every year there is probably about a million hips going every year, year-on-year so this is growing number of people who have hip implants and by and large it's a very successful procedures one of the most successful medical interventions in fact and you can imagine you're bedridden you have a prosthetic hip putting and you're out there and you are playing tennis again. So it works for most people, but over a 10-year period approximately 10% of people of prosthetic hip develop this condition called Aseptic loosening and what that involves is the bone into which the prosthesis is mounted over time becomes replaced by a soft rubbery tissue it's called synovial like tissue and so the joint loses it's structural strength and the sufferer loses the ability to work and it's also very painful it causes chronic pain. So purely a man made disease, because you have to have a prosthetic hip in place to develop this condition, many people don't suffer from it, but if you suffer from it the only treatment is to have the entire prosthesis removed everything cleaned out have a new prosthesis putting, so even if the prosthesis is in good condition it no longer fits and it's so it has to be removed, so it's not a case that the prosthesis is broken it's the bodies reaction to the prosthesis.
Fintan Walton:
Sure, yes. So obviously the purpose of this therapy is to clean up all that soft tissue?
Andrew Bray:
Yes, essentially and what's interesting here there has been a number of clinical trials performed using this technology and there was a 12 patients study undertaken in the Netherlands and the patients who received the higher doses they showed incredible benefit from the therapy. So what happens there is that the tissue is injected in a single injection into this synovial-like tissue which basically it's between a you know middle prosthesis and dead bone so it's hardly contained. So the enzymes is in the same way as the other therapy over a suitable incubation time of say two or three days the enzymes produced in these cells the prodrug is then in this case administered in the single injection into that same tissue, a very potent DNA cross linking agent is generated and it causes cell death and essentially it liquefies tissue, so the tissue which is once rubbery like can actually be just flushed out of the joint.
Fintan Walton:
And then you can replace that with some new cement?
Andrew Bray:
That's one way that it could be used, so an interesting thing here Fintan is unlike cancer you could have a great outcome even if you destroy you know 70% of the tissue, so you are not trying to destroy necessarily everything, but if you can remove enough of that tissue to allow the prosthesis to be remounted using an orthopedic cement then the patient make in a number of years of additional use of that prosthesis and if you are in your 70s there is a you know a large number of people who suffer from this problem who can't undergo this major surgery.
Fintan Walton:
Yes, so you've reduced the amount of time in hospitals so there is a help economic benefit?
Andrew Bray:
Absolutely, so you've got two aspects of this there is a group of patients who can't undergo the conventional treatment which is revision surgery and then there is others who you know would obviously would prefer to avoid such major surgery.
Fintan Walton:
Sure, so and that's is in what stage clinical?
Andrew Bray:
That's completed a number of clinical trials and we would be taking that into a Phase IIa clinical trial and we'll be doing that in Europe.
Partnering strategy
Fintan Walton:
And obviously these are all novel therapies presumably at one stage you want to partner these programs?
Andrew Bray:
Yes, that's right in fact we have a strong interest in finding pharmaceutical company partners earlier on in the piece, so our business plan in a nut shell is to develop both of these therapies into Phase II and that might be at the end of Phase IIa or somewhere into Phase IIb and then to look to partner, license, out-license or sell the programs either together or individually.
Fintan Walton:
Andrew M. Bray, thank you very much indeed for coming on the show.
Andrew Bray:
Yes thank you Fintan, it's been a pleasure.
Fintan Walton
Dr Fintan Walton is the Founder and CEO of PharmaVentures . After completing his doctoral research on the genetics of cell proliferation at the University of Michigan(US)and Trinity College (Dublin, Ireland), Dr Walton gained broad commercial experience in biotechnology in management positions at Bass and Celltech plc (1982-1992).
Andrew M Bray
Chief Executive Officer
Andrew M. Bray is presently Managing Director and Chief Executive Officer of BroadVector. Dr Bray has been actively involved in the biotechnology industry since 1988; his background interfaces science, business development and management. He worked for CSL and for sixteen years at Chiron Corporation and Mimotopes Pty Ltd establishing and leading a profitable Australian chemistry and discovery business with an international reputation. During this period he was also actively involved in business development and technology transfer with pharmaceutical companies in USA, Europe and Japan. Dr Bray is a PhD chemist with a strong background in commercially focused medicinal chemistry, organic chemistry and peptide chemistry. He has a strong publication record (71 publications and 8 patent families) in drug discovery and related technology. He has a broad knowledge base in biological sciences, having worked with pharmacologists, immunologists, molecular biologists and computational medicinal chemists. He is a long serving member of the American Chemical Society and the Royal Australian Chemical Institute. Since 2005 his focus has been on the development of BroadVector's technologies, corporate and investment activities leading to an IPO.
PharmaVentures
PharmaVentures is a corporate finance and transactions advisory firm that has served hundreds of clients worldwide in relation to their strategic deal making in the pharmaceutical, life science and healthcare sectors. Our key offerings include: Transactions / deal negotiations; Product / technology valuations; Deal term advice; Due diligence & expert reports; Strategy formulation; Alliance management; and Expert opinion for litigation/arbitration cases. PharmaVentures provides the global expertise to ensure our clients generate the highest possible return on investment from all their deal making activities. We have experience of all therapeutic areas and can offer advice on both product and technology commercialisation.
BroadVector
BroadVector is developing therapies for the treatment of two diseases associated with ageing: early stage prostate cancer and aseptic loosening of prosthetic implants such as artificial hips. In both cases, the new treatment is based upon Gene-Directed-Enzyme-Prodrug-Therapy (GDEPT), a modern strategy that eliminates a target tissue without the need for highly invasive surgery. GDEPT is a sophisticated site-specific drug delivery system that enables drugs of high potency to be made available to target tissues, without having to circulate through the body first. A licensing or trade sale transaction to a major pharmaceutical company would be contemplated during the Phase II program for each project. BroadVector has also developed a preclinical vaccine platform that shows promise as a prime-boost vaccine component. There is potential to out-license the preclinical product to a dedicated vaccine company.