Christopher Anzalone – President and Chief Executive Officer
Arrowhead Research Corporation (ARWR) Wedbush PacGrow Life Sciences Management Access Conference Call August 14, 2012 4:15 PM ET
So, we’re pleased to have Arrowhead Research here presenting at the Wedbush Life Sciences Management Access Conference. And let’s presenting for Arrowhead our Research Corporation, which is a public traded company focused on metabolic diseases or obesity another issues is Christopher Anzalone, CEO.
Thanks very much. All right, so Arrowhead is a targeted therapeutics company and we are focused entirely on gaining drugs, where they can be effective AnginaRex towards, those ends we have developed a number of platforms they enable us to target and to deliver multiple therapeutic mortalities. So we saw – we view these platforms in two primary asylums. One is we have the world largest human right peptide targeting library. This was developed at MD Anderson Cancer Center and we will talk about this in the next couple of slides.
We use these to conjugate the drugs to make peptide-drug conjugates or PDCs. Think of these as next generation antibody-drug conjugate or ADC. We also have extremely broad set of RNAi platforms. This was centered around delivery, but we also have broad premium to operate within RNAi chemistries.
These technologies came from a number of different areas primarily through the acquisition of Roche’s RNAi business back in October of 2011. We have a portfolio of delivery systems and however, we have two primary systems both of which are targetable, they are non-lipid. And so with those we can make targeted RNAi therapeutics. Now we can use those also in conjunction with our peptide library to make targeted – to which make peptide targeted RNAi therapeutics.
Now we are not just an IP company. We have substantial R&D facilities and capabilities. We got about a 24,000 square foot facility in Madison, Wisconsin where our R&D happens. This can also came into the Roche acquisition and what we have there is infrastructure of it that was build by big pharma and that the small biotech would have a very difficult time replicating. And so we have substantial capabilities there.
All right, so why should you care about this well. We are responding to four market opportunities. First, pharma launch to make their APIs better. We have over 42,000 targeting sequences that we can use to target. We think virtually any type of drug to make APIs better. We think we can shift the safety profile of the drug, as well as the efficacy profile of the drug by targeting with these peptides. Second, pharma launch in Richmond strategy what we mean by that is for example if the cancer drug has increased survival by two months, but that really means is that some patients will survive two years longer and some patients will survive two weeks longer. Of course, our goal is to drive the patients that will respond to the therapy into the therapy. We have the capabilities to do that by making companion diagnostics on the back of our targeting library as well.
Next, we want to make generics better. We really like the idea of the business of taking the generic with multiple years of clinical end markets history and targeting that generic to make it either safer end or more effective being as a good business and its really straightforward business.
And then finally of course Parma still needs a way to deliver siRNA, consistently and outside deliver and we have capabilities there as well. So we got multiple value creation points among these four areas and including developing drugs it will be partnered or licensed two foreseeable companies including allowing a foreseeable companies to build our platforms, yes.
Is the platform is in the skincare I thought lot was in the skincare?
In the skincare, we do not have any candidates in skincare at this time.
First of all, it’s ingredients in the skincare all the time, right?
Probably not exactly we’re talking about here. I go into that platform in the next few slides that’s an interesting question now. Okay, now we are not just a platform company, we are also a product company we have a fairly robust for these (inaudible) company product pipeline, for peptide-drug conjugates our PDCs our first candidate or first PDC is called a dipeptide its against obesity. We have begun in Phase I study at MD Anderson Cancer Center about a month ago and so we are dosing patients as we speak. We also have a generic conjugate program in oncology that we are developing that’s still preclinical with in targeted RNAi, we have CALAA-01, which is an oncology, it’s a solid tumor, RNAi therapeutic, we’re finishing the Phase Ib in the next couple of weeks. Our next RNAi therapeutics is called ARC-520 that is again hepatitis B and we believe that we can file an IND in the second quarter of 2013. And we also have follow-on programs within our RNAi program, RNAi platforms probably the most advanced is against renal cell carcinoma.
Now I’ve got these two hepatitis in ARC-520 because read we think that those are potentially attractive to partners early. And the reason is because they’re both serving or addressing large underserved markets, we got very [contaminant] preclinical data in both we got unique amount of action in both, and we’ll talk about that in next several slides. And the trials are designed to provide early efficacy signals in both of those.
All right, so we’ll start with the homing peptide platform. So there is a technique called Phage Display that’s been around since the late 80, early 90s that is well validated and used in experimenting animals quite often, it involves using harmless viruses called Phage that have expressed on their heads peptide sequences.
What researchers can do is make a library of these Phages with a random sequences on their heads and then inject them into animals these billion of Phages will go everywhere and they were just by random chance buying to certain receptors and be taken up by selves, the receptors they’re buying to course are going to be will buying to these very specific sequences, the animals are then sacrificed and you can harvest tissues and find novel cell of receptors as well as peptide sequences that will be taken up by tissue rapidly, so that’s going to run for a while, that’s not revolutionary, what is transformational here is that MD Anderson Cancer Center use this and continues to use this in patients and humans.
So what they have done on restrict that whole guidelines is to treat terminal cancer patients with this Phage libraries, injecting with these Phage libraries and then once the patients die harvest tissues and organs to find peptide sequences that are rapidly taken up by these tissues and organs.
So what we have now is potentially very powerful platform, we got about 1.5 million sequences that are rapidly taken up my multiple cell types in the body. Now from our perspective before using this to shuttle drugs into certain cells, we don’t care so much about those sequences, that are taken up by multiple tissue types, we care only about those sequences that are taking up by only specific cells, so although as we have about 42,000, so still a very large number these cover virtually every tissue in the body, they are rapidly internalize, these are all, they are screen for peptide that are taken up in the first 10 or 15 minutes of injection.
We believe that we’re the only group in the world that has this type of data and we think it’s a largest library again in the world, well this impact is also is that is the conjugation chemistry of attaching these sequences truly small molecule drug or an RNAi drug or peptide drug (inaudible) is reasonably straightforward particularly compared to an anybody.
So again, what we can do is to create these magic bullets attribute guide in therapeutics that will take therapeutics take drugs directly to where they can be effective (inaudible) nowhere else.
All right so we do this as a line graph, if we can really do this and harvest this just potentially revolutionary across multiple indications, now all of these patients where the data were generated are cancer patients. And so we’ve an awful lot of data on peptides that we taken up by [hemovascular] turn by tumors but these patients also had otherwise healthy tissue, and so we can use these four for non-oncology indications and non-oncology drug as well, so the question is will pharma will partner build on this platform we think the answer is yes, because first the science evaluated this is not a new techniques, it’s been used for years they want to think with new ones this is that you’re using that in humans. It is vastly a 1000 of sequences and we cover virtually every cell type in the body.
We also have – we also believe that they will that pharma build on this because of market experience. We are not introducing a new concept because the idea of guided therapeutics has been around from sometimes, it’s been a goal for sometime in antibody-drug conjugates or ADCs I have got an awful lot of attention over the last several years with companies like immune gene and CL genetics that have really have been driving force in this field.
So, we view ourselves or we view this platform as the next generation of ADCs or antibody-drug conjugates. However, we think we have a number of advantages over ADCs. First, we are faster to the clinic. It’s time consuming to find another receptor and then to create an antibody against it and then to humanize that antibody. We don’t have any of those steps, we have sequences now that we can go – we can conjugate directly on the drugs.
We are cheaper than ADCs for the same reason it’s costly to do all those steps. Third, we are potentially simple to develop. The conjunction chemistry as I mentioned to attach a small peptide to a small molecule drug is quite a bit more straight forward than attaching a large antibody. We’re also potentially are more efficient and a stock that on the milligram – per kilogram basis small peptides will deliver about towards the magnitude more drug to the side of action than an antibody.
And finally we have an attractive partnering model, because we have 42,000 of these, we can work, we think economically we’re pharmaceutical partners. We can do with many, many times over, so we are – we can do this many, many times over. And so we can take risk alongside with them and back-end load if you will our partnerships.
So well the (inaudible) we think the answer is yes as well, because of experience with CL genetics and because of experience with Endocyte most recently, our Endocyte site as a drug, it is angulated with fully, it’s a good drug and it’s a really nice idea to target all the receptors, we can do that but again in a much more specific manner. Now also our model is a bit different than cell generic expanding Amgen. What they generally do is if they got conjugation chemistries, they’ve got their own cancer drugs, a partner can come to them with an antibody, they will stick that antibody on to one of their drugs and then the department has the drug or it is just the opposite.
We have this slight variable of peptides and a company can come to us with their own API and then we can conjugate one of our sequence on to that API. We think that is an easier cell, because many companies are API centric is more powerful potentially. Okay, so the first example of PDC for us is the obesity. We don’t have to go over the market here; I think the market is fairly clear, it is potentially the largest pharmaceutical market there is and exchanged a lot over the last several months. It appears that the regulatory stamps is easing with two new approvals over the last several months. We have a unique, but we actually believe and we have a pretty compelling pre-clinical data.
So one of those 42,000 sequences is specific to the vascular blood vessels white fat and so MD Anderson have (inaudible) that if you could take that sequence shown here in blue and cyclize it and then attached to that sequence, a killer sequence or a Peptide sequence that will reduce a pop business once we get some cite peptide that if you create this conjugate in genetic subsequently in to an animal, it will go everywhere but will only be taken up by the vessels of tissue white fat, you will kill some of the vasculature causing some that white fat to die in the whine and animals loose weight, that was the theory, as they’ve kept back in 2003 and published in 2004 in major medicine and it just worked.
These two animals look the same 28 days prior, stunning these animals lost about a third of their body weight in just 28 days. So there was immediate milestone one can imagine and there was a lot of interest in this. Now one of the reviewers of that paper is going to Randy Seeley, who was the well known of obesity expert. Excuse me, even he said, he can believe board, so he bought two hepatite from a commercial vendor and tested themselves in his own laboratory that is focused in metabolic areas, any found if it just works CPA, he reproduce the data with what they were generated at MD Anderson and we have been studying up to the last seven years. What he is found is that, it is highly effective, he has also found that’s it for me, thank you.
Excuse me, he has also found there is a primary way that works, is by decrease in hepatite, So what he said is that to be the conjugant goes into vasculature of white fat, it seems out some of the vasculature, the white fat does comes hypoxic that seems a signal back that at range of decrease couldn’t take. The theory is that fat has the values of the body of course as an energy store, but it’s kind of cost as well and the cost is, you’re going to maintain these cells and once those cell become hypoxic, it tells the brain that the cost has become too high and so we got to decrease hepatite. So for us that was an hormone for few reasons; first, we have independent validation over multiple studies over multiple animal models from a third-party laboratory that has no interaction with us or MD Anderson.
Second, we are getting CNS effect without being in a CNS drug, the primary mode of action here says is by decreasing hepatite a broad drug definitely getting in the brain, so we were leveraging the bodies own feedback system to decrease hepatite. And third what we’re getting in these animals is a decrease hepatite while they are losing weight of course the obese usually happens when the person is on a diet, they are hungry because their body is trying to invent the prior ways. And the opposite happens here, so from market standpoint that’s compiling to us. Okay, so then when to later went into primary since that similar results there of course full battery of tox and got into humans, we began dosing humans about a month ago. Now, we think that we can have data sometime in the middle of next year in this program.
Now one thing he did mention as well, it’s interesting is not only do we have a rapid effect on weight, we also have a rapid effect on pro-diabetic markers. (inaudible) group showed was in the course of two to three days even before the animals lost weights, we see advantages in triglycerides.
We see advantages in insulin resistance and glucose tolerance. So it’s interesting for us because it opens up another (inaudible) potentially. Okay, we have one more proof of concept for targeting. At MD Anderson in one of their early screens getting the first screen human screen found that in prostate cancer patients and primary tumors, as well as endowment – disease there is a self-service receptor, they are looking 11 receptor that is especially on surface of those cells and nowhere else.
So that was interesting to them. They done with the tissue banks and done the same thing and in prostate cancer patients and so they made a model peptide drug conjugate to look just like the obesity PDC it’s up to the homing sequences different. Now the homing sequence we are buying too and is taken up by this looking 11 receptor with a very small person man study just like patients, where occasions we received (inaudible) once we preferred for four weeks and whether they or not when this time is over they got a biopsy or a marrow biopsy pre-imposed study. The biopsies pre-study work to determine if they were positive for IL-11R receptor and post study was to determine whether or not the drug was actually in dose (inaudible) and whether or not the sales were got.
And what they found was compelling in all six patients. They found positive standing for interleukin-11 receptor pre-treatment in these Domex. In all six patients, they found positive stand for the drug in those sales and not in surrounding sales. And then all those patients based on apoptosis in those cells. And so regards to what you say about the drug, and we think it’s potentially a good drug and this is best part of our portfolio.
It certainly suggests a proof of targeting. So we have just this was part of our acquisition of a company called [Aldose] this in a whole targeting library about four and half months ago. And we certainly had it before looking at this drug, but again at a very at least, it suggested that our targeting platforms do what we wanted to do.
Okay, now moving to RNAi. RNAi was gotten off a live attention for a number of years and then stopped couple of years ago. The world became concerned that delivering these little sRNAs was not going to be feasible. So we always though that if you could solve that problem – solve that delivery problem you could, you could create enough lot of value in that space. And so what we did was we assembled a comprehensive RNAi platform to build around delivery, but also has RNAi chemistry to elaborate as well.
As mentioned, we acquired Roche RNAi business. They invested over $0.5 billion in that business and lot of those assets that we use everyday comes from that acquisition. So we’ve got assets in two primary areas. One is the RNAi chemistry. We’ve got broad FEO within the three primary formats of sRNAs. And then we have very nice technologies in sRNA delivery. Two of which are our focus areas. One is called RONDEL. One is called DPCs or Dynamic Polyconjugates.
The DPCs came in from the Roche acquisition. RONDEL came in from Caltech matters few years ago. So both RONDEL is in the clinic now as a – with appeal of the RRM2, ribonucleotide reductase subunit M2 target, the candidates called CALAA-01 is again cell tumors. The delivery system not to go too much in to it is a very elegant system, it’s a two vial system whereby the components of the delivery system are one vial, and then the siRNA choices in the second vial. They are simply mixed up between the clinic and they spontaneously self establish nano particles with the siRNA encapsulated inside and then decorating the outside of nano particulars are charged malignant.
Now we are using transparent here because in many cell tumors there is up regulation of transparent receptor but we can use any type of malignant we think. And so this is highly amendable to our peptide target (inaudible), we can use those peptides.
So we had a paper in nature two years ago showing some preliminary data from our Phase I, again it’s a solid tumor trial, some of those patients are melanoma patients and so they are easily biopsible. What we showed in some of these patients was first a dose to parent accumulation of our nano particles in the tumors. Second, we showed RNA knock down, third we showed protein knock down and fourth we did primary PCR showing that it’s mediated by the RNA process.
So we think we checked all the boxes. We showed definitely that we could deliver siRNA effectively, in fact we were the first one to do that in man and we are still the only ones to show effective delivery of siRNA in man, and anything but liver. So this is one system, the other primary system is called GPCs or generic polyconjugate, again this came in from Roche. They acquired a company called Mirus Bio in 2008 for $125 million cash.
Mirus was the company that developed this program. When Roche bought it, they were on the first iteration of GPCs and now they’re on iterations 7 or 8. Conceptually, it is similar [trundle] but chemically of course its quite different. It’s made up of a polymer, now we’ve got a polymer backbone. We’ve got multiple classes of polymers and so we can optimize that on a tissue-by-tissue or indication-by-indication basis, it is targetable just like RONDEL shown here with these orange balls. We can use we think virtually any kind of drug in ligand and so we can use our peptide sequences from library in this and we have some very interesting masking chemistry shown here in blue balls that are stable in the blood stream, but Elavil industry recognition.
So the way this works is injected into the body either subcu or ID, that goes everywhere but it’s taking up by target cells via receptor mediated process, once it gets inside the cell, inside an endosome, as the endosome matures incentivize and that causes the masking chemistries to fall off, when those fall off the (inaudible) like the endosome.
The reason I agree is that what this group has developed this platform I knew earlier than most of us knew what that getting siRNA to the cells only half the battle, the other half is getting out of the endosomes and they have very odd chemistry to do that. So this is the technology that really drew us to the Roche acquisition, we had never seen any siRNA delivery that was as efficient as this or as well tolerated as this.
So our first RNAi therapeutic based on this platform is called ARC-520 is to get Hepatitis B. We think it’s a great market, there is over 350 million careers worldwide, there is no cure for it. Hepatitis C therapeutics created an awful lot of value over the last several years and we think Hep B is sort of next drop – infectious disease.
We have really good data on this that will help to distribute published by the end of this year and early next year. So we think we can knock down substantially viral proteins, in fact we’ve got data showing that we can get better than 99% knock down. It’s important because in a world where companies get excited about 75% to 80% knock down and greater than 99% knock down really is remarkable. So we think we can file our IND for this program in the second quarter of next year.
So we are positioned here, we think as a comprehensive player within RNAi we are able to make a diverse array of our target RNAi therapeutics, because our two primary systems are non-lipid based and are targetable, we can go outside deliver. We can treat we think virtually any type of tissue other than possibly the CNS. We don’t believe in getting the CNS right now.
We have a number of potential catalyzes that we will be finishing the CALAA-01 Phase Ib shortly. We’ll have a number of publications coming out by the end of this year and then early next year. We’ll bring HPV candidates ARC 520 in the clinic next year. And we have a collaboration right now with Alnylam delivery. We will continue that and we think we can to get into other collaborations going forward, because of our assets and expertise in the field.
We have a number of milestones over the next 12 to 18 months. We’ve mentioned many of these. We think that we can enter into at least a couple collaborations and partnerships on the targeting side over the next few quarters. We think we can join to at least one RNAi collaboration of partnership over the next few quarters, and again we could well – were you think we can get into the clinic for the HPV program next year and we should have data in the obesity program by the middle of next year.
So strategically, we think that our timing is good. First, targeting is now a major focus for big pharma, coming out of ASCO that was, there was a big takeaway message that pharma is looking for targeting strategies and we think we can cut the world’s largest library of human drive targeting peptide. So we think we can play in that sand box very well.
Second, RNAi is now looking like it’s getting a fresh look by a big pharma, if you look at some of Alnylam’s recent data in a Phase I of the market was receptive to those data. And we think we’re well positioned to take advantage of that as that market comes back.
Third, obesity now, is of great interest. Of course it’s a very large potential market, but big pharma was seen away from that until really just several months ago, when Vivus and Arena showed that the FDA is now appears to be using their guidance.
And then forth, we think hepatitis B is if you will the next is hepatitis C. Hepatitis B we think is a very large market. And we think that large companies are going to toggle to focus on that, over the next several quarters. And again there is no cure for that there is large opportunity. We have very good preclinical data.
So in closing, we do financing or we now announced the financing just yesterday we raised a little bit of money about $6 million. Our market cap right now is up $40 million. So we think that for our size, we have a number of a short-term goal. And for our burn rate about a million two month, we have enough a lot to offer to investors and to partners. And with that, I will stop and answer any questions you might have.
That’s a really good question. So if you look at Vivus and Arena’s drugs what they’ve shown is 5% or 10% weight loss over a year. I think those are probably good drugs, but I think there is enough a lot of market there for a therapeutic they can go beyond that. We saw a dramatic data in roads and even in primates. In roads as I said, we saw 30% weight loss I think it is 28 days. And now I don’t think we want to reduce that kind of weight loss in humans, but gives us an awful lot of flexibility.
You want that.
So given us flexibility on how long a patient can be treated how much for given and we see a large opportunity for us there and that’s just for obesity. The diabetes data we saw was really striking from Randy Seeley’s lab; that was only rodents that we’ll see that if bears out in humans, but Phase I is not exclusively in diabetic patients, but we expected that some other patients will be Type II diabetic or at least a prodrug back if you will and so we will have data on that, I think that our Phase II could be obesity Phase II, it could be a diabetes Phase II. We’ll see but when we see, we see an awful lot of opportunity with that.
Now, if not oral, it’s a subdue injection. We are working on a couple of things right now. We are working on extended release potentially, whereby right now we are looking at one today subdue injection, it’s possible also we are looking at studies with the same construct to see if we can treat once every two days, once a week, what have you and so we’ll see how that fairs out, but even it does not change, we are looking at possible formulations that could be once a month injection, if you will and at least tender lease.
We are not yet looking at oral formulation, all oral delivery at peptide is not straight forward, but people have worked on that and so that’s something we could work on in the future.
Have you seen any vascular issues in pre-clinically with other departments?
Yeah, we know we haven’t. We haven’t doesn’t mean that exist, we haven’t seen it, we have not seen any CB issues either, again doesn’t mean, doesn’t exist we haven’t seen them. The talks we have seen at higher doses is renal in nature. We do see any hypoxic edacity in rodents or in, not even termites but the renal tox has been categorized as mild to moderate and reversible so once (Inaudible) comes up drug any reasons that were formed our result.
No, we saw renal tox in (Inaudible) and in premix, we didn’t see any CV tox or orthopedic tox in any of the species, yes.
Yep, yeah, okay, so the first question [how is] revenue. So that’s an interesting question, so we, when the capital market became difficult a few years ago, we looks to build this company in such a way that we have assets that can be partnered out with big pharma larger companies to provide non-diluted capital.
We think we have done that, what we have in the targeting library is something that is vast and so we can partner out many of those without affecting our long-term upside potential because I can’t make 42,000 drugs, so we think that we can bring in substantial amounts of capital over time, non-dilutive without cramping our ultimate upside potential. Same thing is for RNAi side, we’ve got these platforms that are that can be used for many drugs and we just can't utilize it for all the drugs that is good for them, so we think that partnerships they are also found money, if we partner them on a target to target basis.
So on going forward is not to be divorced from the capital markets, but not to be solely dependent upon them, we’re right now solely dependent upon them, we’re hoping to make that transition at some point and where we start to bring in substantial amount of capital. Now there is a question about financing, it was priced at $2.76, for that, each unit was priced at $2.76, each unit consisted of one share of common stock and one warrant that is good for 0.75 shares of common stock, there is straight price for those warrants are $3.25. There is no (inaudible) protection and like that, pretty clean financing.
No, via a subsidiary of ours that we’re on 80% of has a $1 million of debt that doesn’t have a coupon and that $1 million comes due matures in the fall of 2013. Yes.
We don’t have any revenue to speak off.
Okay. Thank you.
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