Call Start: 12:00
Call End: 12:25
Sangamo BioSciences, Inc. (NASDAQ:SGMO)
UBS Global Healthcare Conference
May 21, 2014 12:00 PM ET
Geoff Nichol - EVP, Research and Development
Andrew Peterson - UBS
Good afternoon. I guess I can say now it is 12:01. Welcome everyone to the final day of the 2014 UBS Global Healthcare Conference. My name is Andrew Peterson; I’m the small mid-cap biotech analyst here at UBS. It’s my pressure today to introduce Sangamo, a leading company in the zinc finger technology space. Speaking on their behalf is their CEO Geoff Nichol. After the presentation there will be a breakout session in the Liberty 3 room, down the hall. Geoff?
Thanks a lot Andrew. I’m not actually the CEO. I am the Executive Vice President for R&D. Thanks for the promotion though. It’s always good. So I will remind you all that I will be making forward-looking statements today, and would refer you to our various filings 10-Qs and 10-Ks for further details.
Before going into our developing portfolio, I would like to talk a little bit about sort of what we have built around at Sangamo. We have built around the zinc finger protein. These are naturally occurring proteins that are circulating within the cells, of every cell of our body and probably of every cell-based organism that exist on the planet. And their job is to act as transcription factors, I’m sure you know what transcription factors are? And they need to be able to find the exact spot in the genome where they need to go to affect the gene that they have been programmed to affect through evolutionary history.
And so it follows their motif, that they have, in a way that’s very similar to the perhaps the CDR region of monoclonal antibody or whatever, is extremely adaptable and engineerable to go to very specific places in the genome with exquisite sensitivity and specificity. And it is that technology which we have learned to engineer with that sort of specificity and sensitivity. We can then use that technology to find any gene we choose and we can either change that gene by editing or we can control the function of the gene. We have developed through our own efforts and working with others, AAV delivery capabilities, and we continue to work very actively in effective delivery capabilities and manufacturing.
The zinc finger proteins are widely used in research as research reagents. They are used to generate transgenic animals or in agriculture, I’ll talk a little bit more about that, manufacturing but our primary interest is in developing human therapeutics. Not just to, perhaps modulate our disease, but actually to reach to the absolute genetic basis of a wide range of diseases, go where the actual disease is caused and make the primary change to essentially engineer a genetic cure of that disease. We have a dominant intellectual property position around the use of zinc finger protein, and I would like to tell you a little bit more about the technology itself, before I go on to describe the portfolio of promising therapeutic products that we are developing.
The zinc finger protein itself, you can see at the top, this is something that we can engineer in our labs to be exquisitely focused on the precise location in the DNA sequence that we want to go to, and then we can do one of two things with that zinc finger protein. We can add a gene regulation domain, either oppressor or an activator. So if we can find the spot that controls the activity of that gene, we can turn it up and we can turn it down, and that’s what you can see on the left-hand side of the slide.
On the right-hand side of the slide, we have developed a way of engineering these ZFPs so that they each contain -- we generated two of them, and each one can contain half of a nuclease enzyme, and they can be engineered to find matching sequences so that those two halves of the nuclease enzyme come together and make a cut at a absolutely specific almost indeed base pair specificity. We can pick the base pair where we want to make that cut and then the cell by attempting to repair that cut, it’s error-prone, so we can essentially knockout the gene at that point and interrupt its function or we can actually add a new sequence into the gap that we create, into the cut that we create to essentially add-in a whole new gene and you can see that ZFP nuclease technology characterized on the right hand side of the slide. We started out in the business of using this in the lab and in agricultural applications. We have established collaborations and partnerships with Sigma-Aldrich and AgroSciences and those have brought in over a $100 million worth of revenue to Sangamo. But it’s more recently that we have got into the area of developing human therapeutics and in the past, two and a half years, we have concluded partnerships with Shire in the area of hemophilia and Huntington's disease with an option for Shire to take, pick two more targets.
And earlier on this year, we concluded an agreement with Biogen Idec around treatment of hemoglobinopathies, both sickle cell disease and beta-thalassemia. And through our own efforts and also through the experience that we are gaining, as we move these collaborations forward, we are working on our own account to continue to grow and prosper a pipeline of proprietary ZFP based therapeutics. This is how we characterize our pipeline on this slide. We have two broad approaches to the way that we introduce the ZFPs into the body. At the top you can see, we use an in-vivo approach and this is driven using an adeno-associated viral vector approach. We can give this systemically as you can see in the right hand top field there. We can actually deliver a corrected gene for example into the hepatocytes in the liver and we are doing that with hemophilia in our partnership with Shire.
But on our own account, we have shown data suggesting that we can then have the liver produce the enzyme replacement therapies required for a range of lysosomal storage diseases. I will tell you little bit more if we go down to the next box, we can actually use AAV to deliver our zinc finger protein therapeutics within the brain and this is what we are doing in our partnership with Shire around Huntington's disease and it’s similarly through an acquisition. We have an ongoing Phase II program in Alzheimer's disease where the AAV produces nerve growth factor within the brain. In the lower part of the slide, you can see the way that we can use our technology ex-vivo. In the very bottom, you can see we can use this in stem cells and we actually do that in collaboration with Biogen Idec where we actually knockout a particular target in hematopoietic stem cells and that’s also the basis of a program that we are developing ourselves to knockout CCR5 in hematopoietic stem cells for the treatment of HIV.
And then finally moving beyond stem cells, we can also take T-cells out of the body and we can use our technology to modify those for the treatment of HIV that I will tell you about very shortly as well as in research applications to modify the use of T-cells in this rapidly growing immunotherapy area for the T-cell treatment of oncology.
So, let’s talk about SB-728, this is an ex-vivo use of our ZFP technology to create a knockout within CD4 T-cells. This next slide is busy but let me talk you through it starting at roundabout 9 O’clock. This shows a cartoon of our zinc finger proteins attached to the two halves of a nuclease which are able to then go in and knockout CCR5 and prevent its expression on the surface of T-cells that we have removed from the body of a patient with HIV. Once that knockout has occurred that cell can no longer express CCR5 and so that the R5 HIV virus cannot then get into the body and this is what happened with the patient you see pictured there Timothy Brown, who received a transplant with a double-knockout essentially homozygous naturally occurring mutation of CCR5 no longer express CCR5 and has remained HIV free without therapy for the past few years since it transplant.
And the first thing that we can do or observe in patients is that we can see reductions in viral load when we take them off the antiretroviral therapy as our cells circulate. And we have data showing that there is a correlation between the number of circulating cells that have complete knockout of CCR5 and this reduction in viral load. And we have studies ongoing where we are evaluating the use of Cytoxan to increase the number of those cells in the body. And finally, we have as you see it round about 8 o'clock on the slide there we have interesting data suggesting that we can reduce progressively over the course of three years the circulating reservoir of integrated HIV in the body in circulating cells and this is certainly unheard of in the setting of patients who are treated with antiretroviral therapy they continue to maintain a reservoir and obviously removal of that reservoir is absolutely crucial for cure of HIV.
So big news for us occurred in earlier on this year in early March when early Phase I trial in collaboration with the University of Pennsylvania was published in the New England Journal of Medicine you don’t get into the original research area of New England Journal of Medicine without being very novel and without having breakthrough potential. And this was breakthrough data it demonstrating the first in man use of a genome editing approach. We’ve demonstrated the safety of this approach the circulating cells safety persist and up here when exposed to HIV to show the expected enhancement of survival that you would expect if protected from HIV entry, we saw a marked increase in CD4 cells as well as a decrease in viral load in several subject that appear to correlate with the level of circulating CCR5 knocked out fully knocked out cells and including one subject who have the end of an interruption of treatment with antiretroviral therapy became undetectable.
So we have a feasible approach to the treatment of HIV and certainly soon after the publication of that data at Croy, we presented data showing that sudden immunological profile helpful to engraftment of the cells as well as data confirming long term reservoir reduction in patients with HIV. Where we’re taking this next is to we have essentially completed a study of patients who have CCR5 knockout on one of the alleles that’s it’s a naturally occurring mutation. And in that setting in a small group of patients we have one subject who was reported at Croy to be off antiretroviral therapy and controlling the own viral load for 31 weeks and counting. And we also showed data showing that by pre-treating with Cytoxan we can increase the engraftment of these cells to the threshold level that we feel based on the statistical analysis of the correlation that would likely lead to significant reductions in viral load in patients with HIV.
We proposed to expand that Cytoxan study to evaluate doses a little higher than the 1 gram that we had reported on at Croy and we will continue to evaluate 12 patients this year and enroll those patients and expect to be showing data next year. We have altered and improved our process moving away from an adenoid viral approach to a messenger RNA elect preparation approach for actually modifying the T-cells outside the body that’s cheaper and much more efficient way of actually manufacturing the cells. And we will continue to evaluate and publish and publicize on the evolution of the viral reservoir in patients and that will there will be updates on that at the next ASGCT coming up in the days following this presentation.
Moving on to another ex-vivo approach. This is knocking out a very important target to treat the hemoglobinopathy both sickle cell disease and beta-thalassemia it’s this is in partnership with Biogen Idec and the idea here is that in the past probably within the past two to three years it’s become clear that the partway that drives the removal of sickle hemoglobin from our circulation in the numb software (ph) bone is driven by BCL11A and by knocking out this BCL11A gene we can cause patients to continue to generate sickle hemoglobin and fetal hemoglobin is known to essentially cure patients who have both sickle cell disease as well as beta-thalassemia. And so it is the attraction of that target and of our unique technological capability of knocking it out in hematopoietic stem cells that led to the conclusion of this collaboration with Biogen Idec.
Changing gears a little bit away from the ex-vivo approach to an in-vivo approach for the treatment of hemophilia and lysosomal storage diseases in hemophilia we are collaboration with Shire, this is an In-vivo approach and the basic approach underlying this is that we’re able to use our zinc finger proteins to find a specific location in the albumin locus and we’re able to then make a cup as I described earlier and insert a gene that can be the gene for generating Factor VIII in hemophilia A Factor IX in hemophilia B or any range of other enzymes or proteins that have therapeutic benefit. You may ask why we chose the albumin gene. And the reason for that is that albumin is produced in large quantities, we produce nearly 5 kilograms of albumin per year. So that you need to co-opt only a tiny fraction of that output to generate therapeutic quantities as you can see of a wide range of therapeutic proteins that we know are already effective in human therapy. So treatment of hemophilia and treatment of lysosomal storage diseases.
We’re applying this initially in treating hemophilia A and B and our Shire collaboration, but it is clearly leverage once we’re able to generate Factor VII or IX from the albumin locus, we simply need to swap out the template design and insert a different protein template and we can treat Gaucher, Fabry, Hunter, Hurler what have you in terms of LSDs and we’ve already published data demonstrating that in [Indiscernible] we’re able to show expression of the enzymes that can reverse these diseases.
And clearly this is potentially highly disruptive to an extremely highly valuable space. There are billions of dollars being made in treating hemophilia and LSDs using protein and enzyme replacements and essentially we will be able to use our technology, if this works out to essentially you have one treatment possibly in the very first years of life that would lead to lifelong production of the curative protein in the setting of these diseases and obviously transform the therapy of circulating protein responsive diseases.
Moving on to another in-Vivo application of our technology, this time in Huntington’s disease as part of our Shire collaboration. Huntington disease is absolutely terrible condition which progressively leads to motor disorders and then failure augmentation and obviously early death. It’s due to an extension of a multiple repeat that you can see in those red bars there very long CAG repeats on allele compared with the blue bars which show the number -- the distribution of repeats in the normal allele setting. And the trick here is to find a technology which is able to leave the normal allele along which we need for neuron health and selectively know down the activity of the mutant allele. And you can see that we have actually across a range of differences between the repeats in the normal and mutant alleles being able to achieve this breakthrough of allele specific repression.
And we’re being with this selective repression we’ve been able to demonstrate a range of both biomarkers as well as animal model outcomes that are highly positive for moving forward in Huntington disease to potentially create a breakthrough therapy using AAV delivery directly into the brain, something which we have being gathering expertise as part of the Huntington program as well as through our acquisition of Ceregene, who have very important knowhow and regulatory filings related to central nervous systems delivery of AAV as well as an ongoing Phase 2 study fully funded by the NIH using AAV delivery to generate nerve growth factor in the setting of Alzheimer’s disease, which we’ll read out next year.
So high level this is our portfolio, you can see that we are targeting ongoing Phase 2 data from our Cytoxan HIV program next year. We’re looking to complete INDs for stem cell program in HIV as well as hemophilia A and B and beta-thalassemia in 2014. And next year in 2015 targeting sickle cell two LSD targets on our own account and with Shire an IND with Huntington program. And also as I mentioned in 2015 our ongoing Alzheimer’s disease program Phase 2 reads out.
You’ll see new data coming up at ASGCT in the next several days. We’ll continue to present ongoing data from our SB-728-T as well as other preclinical programs and we’ll continue our therapeutic partnerships and we'll continue to manage our finances in a responsible and effective way, aiming to end the year -- I'll give you a little more guidance on that in the next slide. We'll be presenting a range of presentations at ASGCT in the next several days and in terms of our financial overview we anticipate as general guidance ending this year in the 225 million to 230 million range assuming the ongoing spend and assuming that we continue to make out timelines on partner programs and gain access to the various milestones associated with that. And to continue into 2015 with very significant maintenance of our cash position in over 200,000 million range.
So in summary, we have a robust platform, we are focusing that on a growing portfolio of breakthrough therapies for a range of diseases in which we are aiming to generate genetic cures. We are moving forward with our in-vivo Protein Replacement approaches with INDs this year and next. We have an IND in treatment of beta-thalassemia later this year. Our Huntington's program is moving extremely forward successfully and we continue to report on ongoing positive data in our HIV program. We have a flow of INDs in the next two years and we aim to build a significant portfolio with significant upside opportunity, once we past proof of concept in each of the areas that are described in the years ahead. And we have the cash and financial management to allow us to do that.
So thank you very much and look forward to answering any question in the breakout immediately following this talk.
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