Sangamo Therapeutics Inc (SGMO) 2010 Q3 法說會逐字稿

Good afternoon, and welcome to the Sangamo BioSciences teleconference to discuss the third quarter 2010 financial results. This call is being recorded. I will now pass you over to the coordinator of this event, Dr. Elizabeth Wolffe, Director of Corporate Communications.

Thank you, Jevon. Good afternoon and thank you for joining Sangamo's management team on our conference call to discuss the Company's third quarter 2010 financial results. Also present during this call are several members of Sangamo's senior management, including Edward Lanphier, President and Chief Executive Officer; Ward Wolff, Executive Vice President and Chief Financial Officer; and Dale Ando, Vice President of Therapeutic Development and Chief Medical Officer.

Following this introduction, Edward will highlight recent activities. Ward will briefly review third-quarter financial results for 2010, and Dale will update you on progress in our ZFP therapeutic program. Finally, Edward will summarize our current guidance and our goals for the remainder of the year. Following that, we will open up the call for questions.

As we begin, I'd like to remind everyone that the projections and forward-looking statements that we discuss during this conference call are based upon the information that we currently have available. This information is likely to change over time. By discussing our current perception of the market and the future performance of Sangamo with you today, we are not undertaking an obligation to provide updates in the future. Actual results may differ substantially from what we discuss today, and no one should assume at a later date that our comments from today are still valid. We alert you to be aware of risks that are detailed in documents that the Company files with the Securities and Exchange Commission, specifically, our quarterly reports on Form 10-Q, and our annual report on Form 10-K. These documents include important factors that could cause the actual results of the Company's operations to differ materially from those contained in our projections or forward-looking statements. Now, I would like to turn the call over to Edward.

Thank you, Liz, and thank you all for joining us for our conference call to discuss our third quarter results for 2010. Let me begin by briefly recapping a few of the events of the third quarter which highlight our progress towards our goal of demonstrating the utility of our proprietary ZFP platform as a new class of therapeutics that function at the DNA level.

We published groundbreaking preclinical data in the scientific journal, Nature Biotechnology from our ZFN mediated stem cell therapeutic program for HIV/AIDS. This approach is based upon the use of our zinc finger nuclease, or ZFN, technology to disrupt the CCR5 gene in human hematopoietic stem cells, or HSCs. Disruption of the gene in HSCs enables us to make a permanent change which is carried through to all the cell types in the immune system.

The publication of these data generated a great deal of interest in our HIV program and our technology in general, and resulted in a number of articles, including a feature in the Los Angeles Times, which was widely picked up by other news outlets.

The generality of our ZFN CCR5 program forms the basis for a very promising therapeutic strategy which we are pursuing at a number of levels. The stem cell work published in Nature Biotechnology was carried out by Sangamo scientists and collaborators at the University of Southern California. You may recall that last September, along with a third group from City of Hope, we were awarded a $14.5 million Disease Team grant from the California Institute for Regenerative Medicine, or CIRM, to bring this therapy to the clinic. This is an important program for us as methods that we establish for delivery of ZFN and subsequent processing of modified cells will translate to other stem cell-based ZFP therapeutic products.

Additionally and already in patients are two Phase I clinical trials to evaluate the safety and numerous clinical parameters of ZFN disruption of the CCR5 gene in CD4-positive T cells. This effort is going very well, and we will have more to say about these trials, our plans to provide data from these trials, and a new Phase I-II trial in HIV later in the call.

We were also awarded a second grant from the Michael J. Fox Foundation for Parkinson's research to fund experiments in primates to develop ZFP therapeutics for Parkinson's disease. This is an important vote of confidence for our approach and for the positive preclinical data that we had already obtained in a rat model of Parkinson's with our ZFP activator of the growth factor GDNF. The $895,000 award is being paid over a two-year period.

We have also seen continued progress in our collaboration agreements with Sigma-Aldrich and Dow AgroSciences over the past several months. In September, Dow announced ZFN-based exact precision technology platform agreements with KWS, a Germany company focused on sugar beets, and with Wageningen, a second European group to work on starch quality in potatoes.

Sigma continues to expand its range of ZFN-based products adding new cell lines for oncology research to its genome editing kits, a growing catalog of transgenic rat models, and off-the-shelf as well as custom ZFN reagents. Sigma also continues to feature the technology in investor presentations and quarterly calls, and to advertise their ZFN products widely and effectively.

We are benefiting from all of these activities in two important ways -- from royalty revenues, from Sigma product sales, and from an exploding interest in our technology by scientists and labs across the world and throughout the life science industries.

But before we go into more detail about our therapeutic programs, let me hand the call over to Ward for an update on our third quarter financial results, as well as our financial guidance for the remainder of 2010. Ward?

Thank you, Edward, and good afternoon, everyone. As you know, after the close of the market today, we released our financial results for the third quarter ended September 30, 2010, and I am pleased to review the highlights of those results. Revenues in the third quarter of 2010 were $2.9 million compared to $4.1 million for the 2009 quarter. The third quarter 2010 revenues were primarily comprised of revenue from our collaboration agreements with Dow AgroSciences and Sigma-Aldrich agreements in protein production, as well as $700,000 of revenue from research grants.

The decrease in collaboration agreement revenues from $4 million to $2.2 million was primarily due to the completion of the research team's term of our commercial license agreement with Sigma in July 2010, and to a decrease in amortized revenues associated with a commercial option fee paid by DAS in 2008. The increase in research grant revenues was primarily due to revenues in connection with Sangamo's portion of the Disease Team Research Award from the California Institute for Regenerative Medicine and research funding for the Michael J. Fox Foundation for Parkinson's research.

Total operating expenses for the third quarter of 2010 were $11.7 million compared to $8.9 million for the same period in 2009. Research and development expenses were $8.8 million in the 2010 quarter and $6.2 million for the prior year quarter. The increase in R&D expenses was primarily related to our clinical trials of SB-509 in diabetic neuropathy, and SB-728-T in HIV/AIDS.

General and administrative expenses were $2.9 million in the third quarter of 2010 compared to $2.7 million in the 2009 quarter.

For the third quarter of 2010, we reported a consolidated net loss of $8.7 million, or $0.19 per share compared to a net loss of $4.9 million, or $0.12 per share for the third quarter of 2009. For the nine months ended September 30, 2010, revenues were $16.1 million compared to $11.9 million for 2009, and operating expenses were $32.7 million compared to $28.9 million for the same period in 2009.

Turning to the balance sheet, we ended the third quarter of 2010 with $63.1 million in cash, cash equivalents, and short-term investments. Our net cash used in operating activities was $6 million for the third quarter.

I am pleased to say that we remain on track with respect to our operating plan for 2010, and we are maintaining our financial guidance reiterated on our second quarter call in July, of having at least $60 million in cash and investment balances on hand at the end of 2010.

In previous calls we explained that the cash guidance and our usage estimate translated into anticipated GAAP revenues in the $18 million to $22 million range, and GAAP operating expenses in the $43 million to $47 million range for the full year 2010. These GAAP metrics remain in place.

As you will recall, this guidance assumes no new financing or partnerships, but it does include anticipated milestones and revenues in 2010 from our existing partnership agreements.

Thank you, and I will now turn the call back over to Edward.

Thanks, Ward. In addition to research grants and funding from the Juvenile Diabetes Research Foundation for our Phase IIb trial of SB-509 in diabetic neuropathy, our partnerships with Sigma-Aldrich and Dow AgroSciences continue to provide nondilutive revenues which partially offset our ongoing investment in our ZFP therapeutics programs.

As such, we have been able to carefully manage our cash burn, and with $63.1 million in cash at the end of the third quarter, and expected milestones and license fees in the fourth quarter, we are on track to meet our goal of ending 2010 with at least $60 million in cash and cash equivalents.

Importantly, we have kept spending in hand while aggressively pushing towards our ultimate goal, which is to establish our ZFP technology as a new platform for the creation of novel therapeutics that function at the DNA level. We, our partners and more recently their customers, have provided clear demonstration of the power and the generality of our technology. To achieve validation of our ZFP technology as a viable drug development platform, we are prosecuting clinical trials of both arms of our technology to generate clinical data that demonstrate the safety and efficacy of ZFP therapeutics.

To that end, we have been working to advance programs in our gene regulation technology with SB-509 in multiple Phase II trials and an ongoing Phase IIb trial in diabetic neuropathy. More recently, we initiated Phase I clinical trials in our ZFN mediated gene editing technology for HIV and glioblastoma.

As I mentioned earlier, I have asked Dale to update you on the progress of these ongoing clinical programs, particularly our HIV programs, and our expectations for the release of clinical data from individual studies. Dale?

Thank you, Edward. As most of you know, this is a very busy and exciting time in the clinical development of our ZFP therapeutics pipeline. Over the next 12 months we expect to have data from all of our ongoing clinical trials. Our zinc finger nuclease, or ZFN gene modification technology is changing the face of biology by enabling modification of genes in cells with unprecedented efficiency and specificity.

Naturally enough, we are very excited to be evaluating this technology for the first time in man, and are particularly pleased with the progress of our first trials, which are part of a broader program to develop a therapeutic for the treatment of HIV/AIDS. There are actually two ongoing Phase I trials of this therapeutic candidate, SB-728-T, one at the University of Pennsylvania in collaboration with Carl June, and our own dose escalation trial here in California. Both used ZFN to disrupt the CCR5 gene in the subject's own CD4 T cells, although each clinical group is focused on a slightly different HIV patient population.

CCR5 is a well validated target for HIV. This is a naturally occurring mutation in this gene, the CCR5-delta 32 mutation, which occurs in about 1% of the population of the US. This mutation results in a nonfunctional CCR5 protein and makes these individuals who are otherwise normal, resistant to infection from the most common form of the virus.

Further evidence demonstrating the importance of CCR5 in HIV infection was provided in an experiment carried out by doctors in Germany on the now famous Berlin patient, who was infected with HIV and also had leukemia. This individual received the bone marrow transplant from a donor who carried the CCR5-delta 32 mutation. The patient was able to stop his antiretroviral therapy and three years later the virus has not returned. It is not an exaggeration to say that the result of this experiment, although only an N of 1, has shaken up the HIV research community and is part the reason that clinicians and scientists in the field are cautiously beginning to talk about the possibility of a cure for HIV.

However, it must be kept in mind that the Berlin patient required an allogeneic transplant from the tissue match CCR5-negative stem cell donor, and the chances of finding such a matched donor of cells for each individual HIV patient are very slim.

Our ZFN technology can be used to specifically and efficiently disrupt the CCR5 gene to produce a similar outcome in both human CD4 T cells and, as you heard earlier, in human hematopoietic stem cells.

In contrast to the Berlin patient, which required a matched CCR5-negative donor to be identified, our technology enabled for the first time the engineering of a specific modification such as the CCR5 mutation in any individual's own cells. We have published data that demonstrates that we can disrupt the CCR5 gene in these cells with a high efficiency and specificity, making them resistant to HIV infection.

In an animal model of infection, the ZFN-modified cells behaved normally in grafting and trafficking as expected, and selectively expanding in the presence of the active HIV infection. Moreover, in the case of the stem cells, the presence of ZFN-modified cells controlled HIV replication in the animals.

These compelling preclinical data that demonstrate protection of modified cells from HIV infection and the selective growth advantage of these modified cells in the presence of an HIV infection provide an important key to improvement of the CD4 T cell compartment.

A naturally occurring example of this is the subgroup of HIV-infected subjects known as elite controllers, who are able to (inaudible) their CD4 cells and control their HIV infection for up to 20 years without requiring antiretroviral therapy. The CCR5 modification is one key genetic difference that has been identified in these subjects compared to those who can't control the viral infection.

With these data in hand, we are understandably excited to be evaluating our ZFN CCR5 T cell product in man. The procedure is as follows.

Cells are collected from an HIV-infected subject by a routine leukapheresis protocol, and the CD4 T cells are treated with ZFNs designed to specifically disrupt the CCR5 gene. These cells are processed, grown and cleared through various quality control tests for release and then reinfused back into the subject all in an outpatient setting.

As you will recall, Sangamo's Phase I trial is nine subjects who are on antiretroviral therapy, have well controlled virus in their peripheral blood, but have lower CD4 T cell counts than expected. The trial consists of three cohorts of three subjects, each of which will receive increasing numbers of ZFN-modified T cells.

The UPenn trial employs the same cell processing procedure but uses only a single dose level and, as I mentioned, is recruiting subjects with different characteristics and disease interventions, such as a structured treatment interruption, or STI, to evaluate effects on viral load post-treatment with SB-728-G.

Both of these clinical studies are first and foremost safety studies, as this is the first time any ZFN product has been administered to humans. We need to ensure that the procedure is safe and well tolerated.

You may recall at a Keystone conference earlier this year, Carl June reported that SB-728-T was safe and well tolerated by the first subject treated. He also went on to report that in this patient they observed persistent expansion of the ZFN-modified T cells.

In the Sangamo trial, we are also evaluating the engraftment and persistence of the ZFN-modified T cells that are reinfused, how they distribute in the body, whether they traffic normally to lymph tissue such as in the gut, and whether they have an effect on the overall balance of the immune system. Specifically, the total CD4 count and the ratio of CD4 to CD8 cells in the body, which is often thrown out of balance in immunocompromise for HIV-infected individuals. While we measure viral load, these subjects remain on their antiretroviral drugs throughout the study, and their virus is well controlled and below detection.

I am very pleased to announce today that we have completed the accrual of all nine subjects on our trial. While we are still very early in the data collection phase of this study, I am very encouraged by the consistent expansion of the ZFN-modified T cells.

In addition, we have obtained IRB approval to expand this trial to include a fourth cohort of subjects that are failing HAART therapy and are therefore expected to have a measurable viral load. As I said, we are very excited about this trial in our ZFN CCR5 gene modification approach to HIV therapy.

And I am happy to report that our enthusiasm is shared by the organizing committee for the 2011 CROI, or CROI meeting, or more formally known, the 18th Conference on Retroviral and Opportunistic Infections, which will be held in Boston from February 27 through March 2, 2011. The conference organizers have invited Carl June from UPenn to give an oral presentation on our data from the SB-728-T trials. In addition, we have submitted our own abstract of the data. We aim to present our clinical data at relevant scientific and medical conferences. And as this is one of the very best forms for HIV research, we are delighted that our initial clinical data will be featured at CROI.

Paula Cannon, our collaborator at USC, has also been invited to present our recently published work on the ZFN disruption of the CCR5 gene in stem cells.

Further and also based upon these early but very encouraging data from the SB-728 trials, I am pleased to announce that in addition to expanding our existing trial to enable us to enroll subjects that are failing HAART, we have obtained approval to initiate a new Phase I-II clinical trial in subjects with HIV. We are particularly interested in the impact of SB-728 early in the course of the HIV infection, both from a therapeutic point of view and because it allows us to study patients who have not been exposed to antiretroviral therapy, or ART, A-R-T.

This new study will accrue subjects to have a CD4 T cell count that is greater than 500 cells per millimeter cubed, but are not on antiretroviral therapy. The current standard of care for HIV-infected individuals is to wait to prescribe antiretrovirals until their CD4 counts are 500 or below. Normal CD4 counts are around 1,000, and it may take 10 years post initial infection for counts to decline to these levels.

These individuals have good but declining CD4 T cell levels, and may have an immune system which has a more robust, anti-HIV repertoire of T cell activity. The virus reaches a so-called set point where destruction of the CD4 T cells and control of HIV replication is balanced. Infusion of autologous ZFN CCR5 modified T cells has the potential to alter this balance in favor of the CD4 T cell and enable enhanced control of viral replication.

Importantly, these individuals also have a measurable viral load that will enable us to assess the behavior of ZFN-modified CCR5 disruptive T cells and the immune system in general when under the selected pressure of active HIV in the peripheral blood. They will be regularly monitored to keep track of the viral load and their rate of CD4 cell decline.

We are planning to enroll 14 subjects who are not on antiretroviral therapy, who have a good CD4 level and a measurable viral load in their peripheral blood. They will receive a single dose of ZFN-modified cells, and we will collect data as before on the modification frequency, engraftment, distribution, persistence and selective expansion of the ZFN-modified cells, as well as the total CD4 counts and viral load. We will update you on the progress of this trial next year, as we expect to present data in Q4 2011.

So, in summary, as I said at the beginning of this update, this is a very busy but very exciting time in the clinical development of our ZFP therapeutics pipeline. While we did not discuss it today, we are deeply immersed in our Phase IIb SB-509-901 trial in subjects with moderate severity diabetic neuropathy and remain on track to present data from the study in approximately 12 months.

We will also be presenting the full dataset from our SB-509 ALS Phase II study, which is consistent with our earlier reported data at the Annual Meeting of the Society for Neuroscience on November 17.

Finally, based upon early but very encouraging data from our HIV CCR5 ZFN Phase I trials, we are expanding our initial study and are initiating a new Phase I-II study to aggressively move this product toward clinical proof of concept and eventual commercialization.

I sincerely look forward to updating you on all of these exciting programs over the next 12 months. And with that update I will hand it back to you, Edward.

Thank you, Dale. We are very pleased to be able to give you an update on the significant and very encouraging process that we have made in our HIV clinical program. As Dale described for you, we have completed accrual of Sangamo's Phase I trial in HIV, expanded this trial into a new group of subjects, those failing HAART, and initiated a new Phase I-II trial in HIV-infected individuals that are not on antiretroviral therapy. Both of these groups have a measurable viral load and allow us to expand our evaluation of this therapy to determine how these modified cells perform in a situation in which they may have a selective advantage over unmodified cells.

In conclusion, our third quarter activities clearly demonstrate our progress and continued focus and execution on our goal to establish CFP therapeutics as a new and highly differentiated class of human pharmaceuticals. We look forward to presenting data from our ALS program at the Society for Neuroscience Meeting in November and, as Dale mentioned, we will use the 2011 CROI meeting in late February to present initial data from our HIV trials.

We also look forward to updating you on our progress at the Lazard Capital Management Seventh Annual Healthcare Conference on November 16 and 17 in New York. This completes our prepared comments. I would now like to open up the call for your questions.

Thank you. (Operator Instructions) And our first question comes from Liana Moussatos with Wedbush.

Thank you. Based on the initial data that you have seen so far with the HIV trials, which kinds of patients can you see being treated with this treatment?

Thanks, Liana, this is Edward. I'll give a comment and then maybe Dale would like to expand. I think we are still early in this, and I think that is probably a great topic to discuss once both Carl June and perhaps our groups present at CROI. I think post the data and us being able to really discuss the data, I think we are going to be in a much better position to really then begin to give you a sense of where we think the optimal population for treatment is.

But I think you can get a sense, also, from what we're going in terms of the expansion of the trial into HAART failure patients as well as into the treatment-naive population, so patients where we will be able to look at changes in viral load. I think it gives you a sense of at least the initial direction we're going. Dale, do you want to expand upon that?

We are basically segmenting the HIV population to three groups. One group pre-treatment with HAART, a measurable viral load. And the second group on HAART therapy with either an unmeasurable [and] measurable viral load. And I think the studies that we have outlined that we are initiating that will get data the next year will help us better understand which one of these three groups that we need to focus on with this product.

Thank you.

Thanks, Liana.

Our next question comes from the line of Charles Duncan with JMP Securities.

Hi, guys. Thanks for the update. I guess I had a question, first of all, on the ZFN program that you outlined. Edward, I know you're not going to tell us what data will -- what the data are that you will be presenting, but could you perhaps give us some insights on, first of all, is this clinical proof of concept or is it really technological proof of concept? And what are the key things that you are tracking on to decide whether or not to continue to develop or to invest further in the program?

Well, you're right, Charles, we won't go into any specific data today, but let me try and address it. I think, again, I'm going to wait until the data are presented at CROI to really characterize where we are in all of this, and so I am not going to talk about clinical proof of concept. I do think there is a good point around technical proof of concept. Can we take autologous T cells? Can we modify them with zinc finger nucleases? Can we characterize those cells? Can we reinfuse them? And as we said from the early data out of Carl's work, are those cells persistent? I think that's a good indication of technical proof of concept.

In terms of the kinds of things we are looking at again, I'll repeat things that Dale said, and then if he wants to expand, I'll certainly turn it over to him. But first and foremost, we are looking at the safety of these modified cells. With that said, we are going to then look at a variety of clinical parameters, and I'll repeat some of the things that Dale mentioned. We will evaluate the engraftment and persistence of these modified cells after they are reinfused. We will evaluate how they distribute in the body and particularly whether they traffic normally to lymph tissues, such as in the gut. We will evaluate whether we see an overall change in the balance of the immune system, specifically in terms of total CD4 count, and the ratio of CD4 cells to CD8 cells in the body.

So, I think those are going to be some of the important clinical parameters beyond the safety and tolerability and persistence of these cells that we will be reporting on at CROI. Dale?

The only thing you might talk about is just anything on terms of selective expansion, but I think that is going to be more in the context of some of the other patient populations.

So, Charles, I think that would be how we would address those questions.

Okay. Dale, perhaps I could ask you if you could give us some insight on how you decided on the number of patients and the trial design for the next step?

Well, I think with the set of size of 14, given the manufacturing requirements, I think is a practical size for obtaining that data in the next year. I think part of the trial design in terms of choosing the types of patients was that the original design preclinically and in vitro work was a thought that these cells would be protected against HIV, and that an active HIV infection would actually selectively expand these cells in a setting where there is a very prominent HIV infection. I think moving to patients that have measurable viral load in their blood, I think is a very important sort of immunologic feature and was one of the primary scientific features in which we developed this strategy in the first place.

So, I think in terms of design structure, the original intent and the human experiment with the CCR5 Berlin patient or the protected patients very strongly suggest that we should be able to take advantage of the selective expansion.

Okay. And final question for Ward. Ward, do you anticipate in 2011 to see any significant increase in your R&D expenditures?

Ward Wolff; Well, Charles, we haven't given guidance on 2011 yet, but we will do that at the year-end call. But I think that as a management team, I think we are going to be pretty focused on proceeding with the multiple programs with a fairly level cost structure intact. If anything, we might see a little bit of a fall-off based on the wind down or the initial costs with respect to the 901 DN trial. But, again, it's early days, but directionally I think you can expect that it would be somewhat consistent.

Okay. Thanks for the added color, guys.

Thanks, Charles.

(Operator Instructions) And I am showing no further questions in queue and would like to turn it over to our speakers for any closing remarks.

Thank you. We'd like to thank you for joining us and we look forward to speaking with you again when we release our fourth quarter and year-end financial information. We will be available later today if you have any follow-up questions. Oh, and one more thing -- Go Giants!

Ladies and gentlemen, thank you for your participation in today's conference. This concludes the program, you may all disconnect. Everyone have a great day.