Voyager Therapeutics, Inc.
Q4 2017 Earnings Call Transcript

Published: 14 Mar 2018

[Operator:]

Good morning and welcome to the Voyager Therapeutics Fourth Quarter and Year-End 2017 Financial Results and Corporate Highlights Conference Call. At this time, all participants are in a listen-only mode. Following the formal remarks we will open the call up for your questions. Please be advised that this call is being recorded at the company's request. At this time, I would like to turn it over to Matt Osborne, Voyager's Vice President of Investor Relations and Corporate Communications. Please proceed.

[Matt Osborne:]

Thank you, Shannon. Good morning and welcome to the conference call. This morning we issued a press release, which outlines the results and corporate highlights for the fourth quarter and year end of 2017 and provides our corporate goals and the financial guidance for 2018. The release is available at voyagertherapeutics.com. Today on our call, Steve Paul, Voyager's President and CEO, will briefly discuss our recent corporate and program highlights; Bernard Ravina, Voyager's Chief Medical Officer, will review the Parkinson's disease program; and Jane Henderson, Voyager's Chief Financial Officer and Senior VP of Corporate Development, will review the year-end financials and then we will open up the call for your questions. Before we begin, just to remind you that the forward-looking statements included in this call represent the Company's view as of today, March 14, 2018. Voyager disclaims any obligation to update these statements to reflect future events or circumstances. Please refer to today's press release as well as Voyager's filings with the SEC for information concerning risk factors that could cause actual results to differ materially from those expressed or implied by such statements. With that, I will pass the call over to Steve.

[Steve Paul:]

Thank you, Matt, and good morning, everyone. Voyager's strong performance in 2017 was evident across many functions of the business including clinical and preclinical development, manufacturing, operations, human resources and business development. This allows us to enter 2018 with an exciting program in Parkinson's disease that is about to enter a pivotal trial, a group of pipeline programs targeting other severe neurological diseases that continue to advance towards the clinic and an exciting new collaboration with AbbVie to deliver monoclonal bodies using AAV that allows us to pursue other important CNS disorders including Alzheimer's disease. For VY-AADC were recently reported longer-term followup data from the Phase 1b trial that we believe continues to demonstrate that VY-AADC can restore the brain's ability to make dopamine and offer patients better control of their motor function in response to levodopa therapy the way they initially did during the earlier stages of their disease. As Bernard will discuss, the goal of this trial and any well-designed Phase 1b clinical trial is to as fully as possible explore a range of doses for both safety and efficacy before proceeding into a pivotal placebo-controlled trial and we have accomplished this with our most recent data set. The results that Bernard will briefly highlight are clinically robust, durable and we believe no due to a placebo effect and we are confident that the design of the Phase 2/3 pivotal program allows flexibility with respect to maximizing our chances of success. Achieving success in this placebo-controlled program we've set a very high bar in the field of Parkinson's disease to address the hundreds of thousands of patients with a one-time treatment and the unique mechanism of action that could provide durable improvements in motor function and quality of life. Our pipeline programs continue to advance with two IND filings expected from the ALS, Huntington's disease and Friedreich's ataxia programs in 2009. Now simply advancing programs into the clinic is not our goal, but advancing potentially best-in-class programs that have a high probability of success once in the clinic is the goal and our ongoing efforts to optimize the capsid, transgene, and delivery approach applies to each of our preclinical programs, our ALS SOD1, Huntington’s disease, and Friedreich’s ataxia programs. For Huntington's disease in particular recent clinical data from antisense oligonucleotide approaches targeting mutant and wild-type Huntington's administered monthly by intrathecal lumbar bolus administration supports development in our view and encourages us with our own gene therapy lead candidate which again will be a won and done approach. However, before we proceeded into clinical development, it is important for us and others to be able to know down the Huntington protein in relevant nonhuman primates in both the cortex and striatum. We believe our delivery approach and optimized vector has the potential for achieving greater Huntington knockdown in striatum than other approaches and importantly sufficient knockdown in the cortex to achieve maximal therapeutic benefit. We look forward to providing you with an update on these preclinical data and advances with this program later this year. Now for Friedreich's ataxia we are also progressing our work using several novel AAV capsids to select a lead clinical candidate. We recently presented encouraging data in a very compelling transgenic mouse model of Friedreich's demonstrating that a one-time intravenous dose of a novel AAV capsid and a frataxin transgene led to a rapid halting and reduction of disease progression measured by multiple tests. With increasing IV doses of our vector we observed complete rescue of the Friedreich's phenotype which are very, very exciting results. Also we have identified an AAV vector that effectively delivers frataxin not only to sensory neurons, but also to the heart in important target tissue for potentially treating the cardiomyopathy in heart failure that eventually proves fatal to so many patients with Friedreich's ataxia. Now, turning to our goals for this year, 2018 will be an important year for the company as our Parkinson's disease pivotal program will be up and running and advancing our other exciting pipeline programs are well within our reach. Specifically we plan to complete a type C meeting with the FDA incorporating feedback from this meeting into our Phase 2/3 pivotal program for VY-AADC for advanced Parkinson's disease. We will provide six months safety and motor function data from the Phase 1 trial of VY-AADC using the posterior infusion trajectory. During mid 2018 we plan to dose the first patient in the planned Phase 2 pivotal program for advanced Parkinson's disease and during the second half of 2018 we plan to provide longer-term safety biomarker, motor function and quality of life data from Cohorts 1 through 3 and from patients in the posterior trajectory trial. We will continue to advance multiple preclinical programs towards clinical trials through further vector optimization and exploration of additional routes of administration leading to filing two IND applications from the ALS SOD1, Huntington’s, or Friedreich’s ataxia programs during 2019. In addition, as we've done with our AbbVie collaboration, we will continue to identify, evaluate and progress business development opportunities, including potentially partnering other Voyager programs as well as our technology platform capabilities. Now, before I turn it over to Bernard, earlier in the year we announced my succession plan which is well underway. Having been with the company for six years since its inception, I take great pride in our accomplishments with the great progress we made with our pipeline and in helping to assemble a terrific leadership team. I will continual in the role of Voyager as a member of the Board and as a member of Voyager's Science and Technology Committee. Given my passion for science and discovering new medicines, I look forward to spending more time with the tau antibody program and our collaboration with AbbVie. Both companies are hitting the ground running on this exciting collaboration. Bernard will now review the progress with our Parkinson's disease program.

[Bernard Ravina:]

Thanks Steve and good morning everyone. We've recently provided the Phase 1b interim update with VY-AADC. I'll briefly recap those results and address some questions that have come up since the readout. At a high level, our first Phase 1 trial has led us to understand the dose response and identify what we think is the maximum tolerated dose or concentration that does not lead to too much dopamine. The second Phase 1 trial using posterior delivery has shown this approach to be a more efficient infusion strategy to take into the pivotal program than the transfrontal approach used in the first trial. This is exactly what we hope to achieve with both of our Phase 1 studies. The data from the first trial shows that one-time administration of VY-AADC increases enzyme activity and decreases the need for levodopa in related medications in a dose dependent manner thus confirming the mechanism of action. The recent data continues to show robust durable improvements in patients motor function along with sustained reductions in daily oral levodopa and related medications in the two higher dose cohorts. At 18 months, Cohort 2 generated a 3.5 hour improvement in quality on-time, or on time without troublesome some dyskinesia which is the primary endpoint of the pivotal program. At 18 months, Cohort 2 patients also had a mean increase of 5.1 hours a day of on-time without any dyskinesia and experienced 65% less off-time. These are very clinically meaningful results especially at this time point. These results are above what one would expect for placebo and they are in the same range as deep brain stimulation in a similar patient population. But diary data represent only to three days of function at a time. For an assessment of how patients are doing over a longer period, we can look at the unified Parkinson's disease rating scale activities of daily living and the patient reported 39 item Parkinson's disease questionnaire or PDQ 39. VY-AADC demonstrated dose dependent, clinically important improvements in both of these measures in Cohorts 2 and 3. These measures indicate overall patient well-being and are reflective of durable and meaningful treatment effects in motor function. So what does this all mean for patients? It means they can count on a reliable and robust response to levodopa as they did early in their disease course. In fact, we know of patients were able to return to work or other activities including a job that involves public speaking. Across the cohorts patients in the trial have been able to return to meaningful daily activities that reflect the high level of motor control including riding a bike and skating. This is really the goal of the program, to return patients to stage when they are able to control their motor function with oral levodopa. We're very pleased with the overall results especially in Cohort 2, given the balance of the durable and improved response in function and wider range to titrate oral levodopa. The combination of the more manageable concentration of Cohort 2 with the potentially greater coverage of the putamen in simpler posterior delivery procedure may be the ideal dose and administration to teach into the pivotal program. Now to address a couple of the questions raised since release of the data. First on durability of response with respect to increase in L-dopa doses observed in Cohort 1 from years two to three. Data on Cohort 2 and 3 now at 12 and 18 months show stable responses over time across multiple measures. Cohort 1 received the lowest dose of VY-AADC which we believe is minimally active based on a small increase in fluorodopa PET signal in modest initial reductions of levodopa. The uptake in levodopa doses after three years is driven by a single subject and must be taken in the context of their overall clinical improvement. Unlike a placebo response, over time this cohort evolved to have clinically relevant benefits as shown by their diary data. In three years after dosing, the cohort on average is better or similar to baseline on all of the relevant motor measures. Given that PD progresses over time, these three-year data are very compelling. Now to Cohort 3 and the plateau from 6 to 12 months on on-time without troublesome dyskinesia. It appears at this one time point, 12 months, we have reached the maximum effective dose with the Cohort 3 concentration. Patients in Cohort 3 on average entered the trial with more severe dyskinesia than patients in Cohorts 1 and 2. They received a higher dose of VY-AADC which resulted in more conversion of oral levodopa to dopamine and more levodopa-induced dyskinesia. This resulted in larger reductions of levodopa and less improvement on diary than Cohort 2. This was not the case in the one patient each in Cohort 1 and 2 who had similar dyskinesia at baseline. This suggest a logical and expected interaction of baseline dyskinesia severity and dose of AADC that is consistent with dopamine pharmacology. For example, in order to balance dyskinesia with good motor control, one patient in Cohort 3 reduced the levodopa dose to 25 mg or less at a time. This is striking evidence of a clinical response given that patients generally take 100 mg at a time when they are first treated. Such small doses however can lead to erratic absorption in instances of variable motor control. These reductions in levodopa resulted in less improvement in off-time and on-time as measured by diary compared to Cohort 2. These results may evolve over time as we've seen in other cohorts and in the preclinical data and underscores that clinical benefit of AADC will be driven by balancing both enzyme or AADC levels in management of the substrate oral levodopa. Importantly, we will apply the lessons from this trial to the design of the pivotal program including dose selection and management of levodopa doses post treatment. Finally, to the pivotal program, given the data from Cohort 2 we're pleased with the design of the program. As a reminder, this is a staggered parallel design with our Phase 2 and our Phase 3 portion. The Phase 2 is powered at 80% to detect a two hour improvement in on-time without troublesome dyskinesia from baseline to 12 months versus placebo. The Phase 3 is powered at 90% to detect a 1.5 hour improvement in on-time without troublesome dyskinesia from baseline to 12 months versus placebo. We're within that range for the Phase 2 and well above that for the Phase 3 given the Cohort 2 data that generated 3.3 hour improvement from baseline at 12 months. Drawing from past placebo-controlled gene and cell therapy trials in Parkinson's disease it showed less than an hour of improvement. This provides us with nearly a one hour buffer going into the Phase 3 trial. In addition the pivotal program will capture many secondary endpoints that are important to regulators, payers and patients themselves. In summary, we're very pleased with the safety, pharmacology of VY-AADC, the durability and magnitude of effect, the results in particular with Cohort 2, and the plans going forward with the program. I'll now pass the call over to Jane who can walk you through our financials in more detail.

[Jane Henderson:]

Thanks Bernard and good morning. I'll spend the next few minutes reviewing the financials and guidance before we move to Q&A. Voyager reported a GAAP net loss of $11.8 million or $0.40 per share for the fourth quarter ended December 31, 2017 compared to $14.7 million or $0.57 per share for the same period in 2016. For the full year ended December 31, 2017 we've reported a GAAP net loss of $70.7 million or $2.64 per share compared to a net loss of $40.2 million, or $1.59 per share, for the same period in 2016. Collaboration revenues were $6.3 million for the fourth quarter of 2017 compared to $2.4 million for the same period in 2016 and $10.1 million for the full year ended December 31, 2017 compared to $14.2 million for the full year ended 2016. Collaboration revenues reflect recognition of payment for research and development services provided by Voyager for various programs under the Sanofi Genzyme collaboration agreement. These revenues can vary based on the quarterly assessments of anticipated efforts under the collaboration. The increase in collaboration revenues for the fourth quarter of 2017 compared to 2016 reflect revenue recognition as a result of Sanofi Genzyme’s decision to not exercise its license option to the ex-U.S. rights to the Parkinson’s program and then Voyager’s recognition of the portion of the agreement allocated to the Parkinson's option. for the full year 2017 the decrease in collaboration revenues compared to the same period in 2016 reflects the changes in the estimated periods for reaching development milestones for certain preclinical programs under the ongoing Sanofi collaboration agreement. As of January 01, 2018 the company has adopted FASB's new guidance on revenue recognition known as ASC 606. So going forward we will make changes as to how we recognize revenue related to our collaboration agreements. We are adopting the new guidance using the modified retrospective approach and will give guidance through the year on revenue recognition for the sanofi and AbbVie collaborations. Therefore amounts recognized as revenue in prior periods will not necessarily be indicative of future amounts to be recognized. Research and development expenses were $13.3 million for the fourth quarter ended December 31, 2017 compared to $12.7 million for the same period in 2016. For the year ended 2017 R&D expenses were $62.3 million compared to $42.2 million for the same period in 2016. The increase in R&D expenses related primarily to the development of our pipeline including the ongoing Phase 1 trial for VY-AADC, and increased personnel and facility costs to support the advancement of our programs. G&A expenses were $5.4 million for the fourth quarter of 2017 compared to $3.5 million for 2016 and $19.7 million for the year ended 2017 compared to $13.3 million for the year ended 2016. The increase in G&A expenses was primarily due to personnel and facility costs to support our pipeline programs. Total cash, cash equivalents and marketable debt securities as of December 31, 2017 were $169.1 million. Now, turning towards guidance, as we enter 2018 with the exciting progress of the Parkinson's program advancing into the planned pivotal stage with the preclinical pipeline advancements including the AbbVie collaboration and with the ongoing investments in manufacturing and to the vector product and genome platform we expect to end 2018 with total cash of approximately $125 million to $135 million. This about includes the $59 million upfront cash payment recently received from AbbVie. We project that our existing total cash will be sufficient to fund operating expenses and capital expenditure requirements into early 2020. The cash run way into 2020 is based on our current operating plan and does not include potential new BD transactions. We remain committed to pursuing business development opportunities around some of our un-partnered programs as well as our platform capabilities. With that, we would now like to open the call up for questions. Operator?

[Operator:]

Thank you. [Operator Instructions] Our first question comes from Charles Duncan with Piper Jaffray. You may begin.

[Unidentified Analyst:]

Hi good morning. This is Sarah on for Charles. So can you just remind me further posterior trajectory the dosing that you are using and how long the procedure is taking at this point in development? And then beyond procedure time what kind of patient reported or other outcomes for example, are pain medicine use will help characterize this procedure as a success?

[Bernard Ravina:]

Thanks, Sarah, thanks for the question. So just a reminder, the whole goal of that trial was really to develop an infusion approach that would be more scalable and efficient for the pivotal program and for commercial. So what we've been able to accomplish in that trial is say 2 to 3 hours off the overall procedure time we're down to 6 to 7 hours range which is given that it's one-time and not staged like DBS puts it probably well under the overall procedure time compared to DBS. So we're very pleased with that and we've gotten very good infusions that we think will be more repeatable and consistent going into the Phase 2 and 3 and then the transfrontal approach we used before. In terms of outcomes, we have basically all the same measures that we had in the initial trial and have been reporting on and will be updating all of you on six-month data that are available for subjects who have made it to that point near the end of the second quarter.

[Unidentified Analyst:]

Great, thank you.

[Operator:]

Thank you. Our next question comes from Jim Birchenough with Wells Fargo Securities. You may begin.

[Unidentified Analyst:]

Hi, thanks for taking the questions. This is Yanan [ph] dialing in for Jim. So first off, could you talk about the baseline characteristics of the patients seen in posterior trajectory trial, in particular I'm interested in the severity of dyskinesia at the baseline and whether it's more similar to Cohort 1 and 2 or it's more similar to Cohort 3? Thanks.

[Bernard Ravina:]

Yes, thanks for the question Yuan. So we will have more for you as we report those results, but overall if you look at the first trial, the range of patients in there is quite representative of what you typically get and the second trial we should have that range as well with patients with more or less severe dyskinesias. We are using the Cohort 3 concentration in that study and so we'll see if it unfolds like Cohort 3 and we'll link that again as we have to our understanding of those baseline characteristics.

[Unidentified Analyst:]

Got it, thanks. And in terms of the AADC enzyme activity, I've forgotten whether you are also measuring beyond six months from treatment. If you do could you share whether in Cohort 1 at three years do you see the same amount of enzyme or is there any change in enzyme levels? Thanks.

[Bernard Ravina:]

So we will be repeating the fluorodopa PET scans which are our measure of enzyme activity. Nobody has had their follow-up yet. That's going to occur in the long term extension study which is just starting up at UCSF that has the longest term follow up patients. So it will be a few months yet. A reminder, Cohort 1 had very modest changes in enzyme activity which is why we refer to them as minimally clinically active dose. And so, looking for durability of enzyme activity there may not be that informative versus Cohort 2 which has good measurable changes and will be able to tell about their stability.

[Steve Paul:]

But let me underscore that. In the academic study that preceded our study, this was done by Professor Bankiewicz, he literally PET scanned patients every year for four years and saw no diminution in two dose levels in AADC enzyme activity. and the monkey data, the non-human primate data, both by Bankiewicz, but also by a group in Japan have shown really stable expression out in the case of the Japanese group to 15 years in monkey. So we think given where we're placing the vector in these very stable neurons, these meetings finding neurons in the putainment [ph] that the expression is going to be very durable.

[Unidentified Analyst:]

Great and lastly, try to understand a little more about the dose titrate adjustment in the pivotal trial design. I think is the dose adjustment may be up to the discretion of the patient according to their feeling of their multi function. So my question is, is that true that is entirely up to the patient and also once the patient dose reviews is there a way to prevent them from overshoot and also could they step back the dose and in case they did overshoot? Thanks.

[Bernard Ravina:]

Thanks for question. So this will definitive management of the substrate levodopa in related medications can be an important part of the pivotal program. And just take a step back, each dose reductions this is not something that people are accustomed to doing and it's a testament to the fact that we're getting real pharmacology here, especially seeing people go down 900 mg or even more that doesn't happen as part of the natural course. So we've learned a tremendous amount in the Phase 1 exactly what you want to do in terms of how to do it and how quickly to do it. The reductions are something that we will provide guidance on for the neurologists who will then work with the subjects in the study. I think what we've learned is not to reduce too quickly. We did see that in the third cohorts and over reductions. Now it's an important lesson that I think we're able to take forward and yes, you're absolutely able to titrate the dose back up and it importantly titration of medication is something that neurologists, Parkinson's experts, in patients with advanced PD are accustomed to doing, but it's almost always on the way up. They're increasing the titrate to optimal motor function and this is just now doing it on the way down. So we're confident in our ability to do that, especially with all that we've learned from these two Phase 1s.

[Steve Paul:]

Yes, as Bernard said, there's a bit of a learning curve here. This is very unusual to go from 1.5 grams per day of LED of levodopa equivalents to down significantly and this is not seen normally clinically, which is one reason we really believe this is working, but there are some lessons to be learned on how best to do this in control motor function and that's what we're doing.

[Operator:]

Thank you. Our next question comes from Matthew Harrison with Morgan Stanley. You may begin.

[Unidentified Analyst:]

Thanks. This is Vikram on for Matthew. So our question is about the upcoming Type C meeting, just wanted to get a sense of what you are looking to get from that meeting, what kind of questions you have from the FDA, what types of issues you're looking to get clarity on, any context you could provide there would be helpful? Thanks.

[Bernard Ravina:]

Sure. So we filed the IND and were given clearance to go ahead with the Phase 2 trial. So in terms of safety, the overall design of the study, the comparability around baculo compared to the triple transfection material, the agency is comfortable with those and really had no comments around those. So the Type C is going to be about the rest of the program in the Phase 2/3. So really what we're going to focus on is how much evidence is needed, what kind of overall and safety dataset. The other things to focus on of course are the endpoints, the analysis plan. The endpoints here are very well established in advanced Parkinson's disease, but we'll be able to understand other things like the role of fluorodopa PET given that this is an enzyme replacement, different than any other Parkinson’s program that has progressed this far. So we'll get an understanding of how they view those evidence, that kind of evidence, and as I mentioned the analysis plan. So I think those will be the key areas of discussion pretty typical at this point in development.

[Unidentified Analyst:]

All right, thank you.

[Operator:]

Thank you. Our next question comes from Christopher Marai with Nomura Instinet. You may begin.

[Christopher Marai:]

Hey, good morning. Thanks for taking the question. Maybe to shift gears here a little bit, I'm thinking about your pipeline. Obviously there's been some great proof-of-concept work establishing Huntington's construct as being potentially helpful in that disease. I was wondering how you're looking at triaging [ph] the opportunity with respect to your pipeline of assets. Obviously you've talk about SOD1 as the next program. You know, help us or walk us through your decision making process there and how we should think about progress going forward? And then just secondarily, remind us of the stereotype you're using there, I think it was an AAV9, as it may be 9 variant and maybe why not use AAV9 and use context given the great proof-of-concept today? Thank you.

[Steve Paul:]

Yes, Christopher great question or questions. So for us the key is adequate delivery and in the case of both the SOD1 program and the Huntington's Program, adequate knockdown in relevant cells in the relevant tissue. So for SOD1 we need to see knockdown of SOD1 up and down the spinal cord in motor neurons and in the brain stem ideally. And frankly, we don't see a lot of that having been done already out in the literature and out in the world today. So we're intent on making sure we can do that before we get into the clinic. Similarly for Huntington's there's a bit more of a challenge in that Huntington's not only affects the basal ganglia, putamen, the caudate nucleus, the globus pallidus, but the whole cerebral cortex. And if you look at a late-stage patient that's very, very evident on a simple MRI scan. So we need to see silencing of Huntington's or knocking down of Huntington's to a sufficient degree. Now the antisense oligonucleotide data that you’re aware of has shown in CSF knockdown of Huntington's in CSF. Now that's encouraging, I agree, but only in so far as it reflects what's happening in the brain and in the cortex in particular. So in our monkey work we now are using, for example, for Huntington's AV1 and we're using sites of administration that we believe will give us very good knockdown of Huntington's throughout the brain and in those relevant brain regions. We're not obviously talking too much about exactly where those sites are, but with that capsid we're reasonably confident we can achieve those goals. And we're going to do that, make sure we do that in a monkey before advancing into the clinic, because if we can't do it in a monkey brain which is larger than a mouse brain obviously, but still much less, much smaller than a human brain, the chances of achieving that in humans is low. But we're cautiously optimistic we can get there and I would advise anyone who is evaluating any of these programs to make sure you've ascertained whether that kind of silencing or knockdown can be achieved.

[Christopher Marai:]

Okay, then when might we see some of the monkey brain data, if you will? Thank you.

[Steve Paul:]

We’re hoping later this year we'll have some more data for you that will convince you of the route of administration and the capsid that we're using.

[Christopher Marai:]

Thanks.

[Operator:]

Thank you. Our next question comes from Brian Skorney with Robert Baird. You may begin.

[Brian Skorney:]

Hey, good morning guys. Thanks for taking the question. Yes, also looking at the pipeline, I was just hoping maybe you can kind of comment a little bit when we look at SOD1, Huntington Friedreich’s ataxia in terms of what you think you're going to have to dose this, where do you think you can get away with local interaction as Friedreich’s ataxia are you thinking that's going to require systemic AV dosing? And then Steve maybe just kind of high level off of that any thoughts on Jim Wilson's recent publications and the risks that you saw highlighting around systemic high dose AV and any concerns on that number one?

[Steve Paul:]

Yes, great question. Just to remind everybody for Parkinson's disease we're going directly into the brain intraparenchymal injections. That avoids very significant systemic exposure. We get great transduction neurons and as you know it looks to be relatively safe at least based on many subjects that have been dosed with AAV2 which is the capsid we're using there. It also obviates the concern about preexisting immunity antibodies that could neutralize the vector before it actually transduces cells. So that one we feel very good about. Huntington's will be the same approach, different capsid and different route exact sites of administration will be different, but again we feel the same way about that program. It's kind of de-risk from some of that systemic exposure data that that Jim Wilson has reported. Now for Friedrichs on the other hand, we are looking at systemic exposure because there we want to get DRG's which are technically neuron, sensory neurons outside the blood-brain-barrier and also we have a capsid that transduces the heart which we're very excited about. And to be blunt, there is still a lot of work that needs to be done there, but using our capsids which are AAV9 derivatives we do not see the same kind of robust toxicity that that Jim Wilson has reported in his monkey studies. Now we're using different monkeys, he is using rhesus monkeys, we're using Cynos. There are differences in the transgene. We’re expressing their slight differences in the capsid. So they're not direct head-to-head comparisons, but all I can say is going up to doses very similar to the ones he used, one time either the fourteenth vector genomes per kilogram we have not seen a fatality yet in any of our monkeys. So we will be reporting on that later this year in a peer reviewed article and also presenting work at the upcoming ASGCT meeting in May.

[Brian Skorney:]

Great. Thanks guys.

[Operator:]

Thank you. Our next question comes from Reni Benjamin with Raymond James. You may begin.

[Reni Benjamin:]

Hey, good morning guys. Thanks for taking the questions. I guess I'm interested in the comparability test. Could you provide a little bit more color on those tasks? Are you looking at both enzyme level then and function? And can you remind us if any patients have been dosed with the new process and kind of as we're waiting for the Type C meeting and the start of the pivotal study, do you plan on exploring more patients at the relevant cohorts?

[Bernard Ravina:]

Thanks for the question. So as you know baculovirus materials been used in clinic and other programs, so there is a precedent clinically and agency of course is well aware that. In our discussions with them and as part of the IND we submitted we had clear criteria in terms of comparing baculo to the triple transfection material that is currently used in clinics. Criteria very straightforward involve the identity right that's AV2 with the same transgene, the same flanking elements. The purity of course as you would have with any release specs and then I think the key of what you were asking about was the potency. Does this make AADC, does it express AADC at the same levels and have the same kind of infectivity? So the answers to those are yes, so that puts us in a good position to really move forward with that material and we're comfortable with our understanding of how those match up on those characteristics.

[Steve Paul:]

Yes, and in addiction for the IND submission, we did a complete toxicology study with the new prep and that was obviously compared with the old prep and the older data that was done many, many years ago, but to achieve and be successful in that tox study, we had to achieve exposures that were comparable and produced enough enzyme activity. These were primarily rat studies, but nonetheless showed very nice comparability.

[Bernard Ravina:]

And I’ll add one other point which is our clinically our measure of expression is of fluorodopa PET scans. We have actually three fluorodopa PET scans in that Phase 2 trial baseline around 45 days and then at the primary endpoint one year. So we'll have an early look to make sure that we're getting good expression in patients.

[Reni Benjamin:]

Got it and maybe just as a follow up, regarding the AbbVie collaboration, can you provide us an idea as to how we should be thinking about the timelines associated with this program as this is something could be seeing an IND in 2019 or is it something that’s quite early and we should really be thinking about 2020 and beyond?

[Steve Paul:]

Yes it's early. It's a discovery research collaboration initially stage one will be for two or three years and then after that hopefully we'll be able to select a clinical candidate. Let me though underscore how excited we are about the collaboration. AbbVie is a terrific company. They have a lot of expertise in monoclonal antibodies, a terrific neuro science group and we like this for several reasons. Obviously we're focused initially on antibodies to Tau which we believe will and could be disease modifying in number of neurodegenerative disorders, Tauopathies and Alzheimer's perhaps, but also this gets us into an area, a new area for us which we're excited about and that is the delivery of monocle antibodies with AV vectors broadly speaking for a whole host of CNS diseases and conceivably non-CNS diseases. So it really does allow us to segue into a brand new platform we believe for the company.

[Reni Benjamin:]

Got it. And I’m sorry, the previous question I had asked about kind of while you're in this waiting period, before dosing the pivotal study does it - would it makes sense to continue to enroll in the ongoing Phase 1 at a given cohort with either the new perhaps [ph] or any of the other changes you’re thinking about?

[Bernard Ravina:]

So no, we’ve really learned what we needed to learn from that posterior delivery study about dosing and you can't readily switch material within a protocol. They're under different INDs, so we’ll do what we said we're going to do, start the Phase 2. We’ll have that PET scan as assurance on enzyme expression and we'll move forward from there.

[Steve Paul:]

Yes, and we'll continue to follow the 22 patients that we’ve already dosed and it will be very interesting to see what happens in Cohort 3 over time as we make dosage adjustments and the like. So we're going to continue to update you periodically on the activity that - the benefits in these patients over time.

[Operator:]

Thank you. Our next question comes from Dane Leone with BTIG. You may begin.

[Dane Leone:]

Hi, thank you for taking the questions. Two from me, one on the PK efforts and then one on the pipeline. Starting with the PK efforts, I wanted to ask in terms of your design of the Phase 2/3 study, how are you thinking about analyses and pre-specified endpoints that could give you some level of - additional level of differentiation clinically on outcomes versus the DBS methods? I appreciate the obviously the differences and the procedure and the calibration et cetera, but just in terms of clinical outcomes, how do you think you can design the study to make it more compelling from an outcomes point of view?

[Steve Paul:]

Gotacha, thanks. I think I understand the core of your question there. How do we really differentiate this based on outcomes of interest from deep brain stimulation and it is a good reminder. All of the patients in our trials were candidates for deep brain stimulation and chose to enter one of these two studies, most of them because they didn't want to have indwelling hardware. In terms of differentiating anything further, the motor function measures are going to be very similar across our studies and what was seen in DBS. And so it becomes a question of magnitude of fact and are there differences across those endpoints, but even more important aspect we think here is that there are clear side effects to deep brain stimulation that we think we may not have. The most important one being cognitive function. So it became clear, a very nice paper published at the end of last year showing that deep brain stimulation, both the implantation of the electrodes in the electrical stimulation caused very specific cognitive deficits. And it makes sense because it's related to where the electrodes are going. So we believe we will not have those cognitive deficits and those cognitive deficits of DBS are clinically significant in communication and kind of attention. So we will be measuring cognitive function and some other behavioral endpoints that might provide a very important point of differentiation.

[Dane Leone:]

Great, thank you and then one on the pipeline if I may. I want to ask since we've hit on some of the To Do list in terms of getting these IND applications, I want to ask as you decide between the different programs or for the two INDs, how much is it factoring in to your decision making process whether these programs that you decide upon may or may not be partnered and/or whether they would be partnered before an IND is filed or after you have some clinical data? And then on the potential of an IP position whether there might be some debate whether you owe someone a royalty or something like that depending on the plate [ph] used?

[Steve Paul:]

Well, just to refresh everybody's memories, so the Huntington's Program and the Friedreich's program kind of remain under the rubric of our Sanofi-Genzyme agreement where they have an opt-in provision once we get into the clinic, the ARS program we have worldwide rights on. At this point, I think we're optimizing for technical feasibility and probability of success and we get good silencing in monkeys with SOD1 and Huntington's we will move those programs forward. We’re as I said earlier cautiously optimistic that we're going to achieve that kind of silencing and knockdown in that case. And from the standpoint of Friedreich’s we're very excited about that program because it's a major unmet medical need, but a very large population of patients relatively speaking. There are some 7000, 8000, 9000 Friedreich’s patients in the U.S. alone today and again given the data we've generated in this mouse model of Friedreich’s ataxia which is where toxin [ph] has been silenced in certain tissues, we see really remarkable correction of that of that disease phenotype. So we're excited about our programs. We're going to move them forward and we're going to base our decision based on our data and what we think the probability of technical success will be moving them into the clinic.

[Dane Leone:]

Thank you.

[Operator:]

Thank you. Our next question comes from Sumant Kulkarni with Canaccord. You may begin.

[Sumant Kulkarni:]

Good morning, thanks for taking my questions. First one is a clarification. Is the piece of recruitment in the posterior trajectory trial as planned, because it appears that there was just one more patient dose relative to the last update during your R&D day?

[Bernard Ravina:]

Yes, it was exactly as planned and we're wrapped up enrolment. So we do have one more patient who was screened before we cut off enrolment, who will be having procedure soon. But no, we've wrapped up enrolment, the key there as I mentioned before is we've learned what we needed to learn and the surgeons at the sites got the experience they needed to take it into the Phase 2.

[Steve Paul:]

And something Bernard mentioned earlier, we recruited seven patients so far in that trial really the last half of last year, very, very rapid recruitment. I think it reflects a great deal of enthusiasm on the part of patients who would otherwise have an opportunity to have DBS, were elected nonetheless to have our treatment. So we're pretty excited about that, we think that augers well potentially for enrolment in the pivotal trial.

[Sumant Kulkarni:]

Sure. And my follow-up is given the number of patients with advanced PD, could you remind us about what interactions you might have had with the FDA on pursuing potential orphan drug exclusivity and what those interactions might mean for perhaps broadening the use of your program in a wider set of PD patients?

[Bernard Ravina:]

Great question, yes. It’s a great question, thank you. So we did have several interactions with both U.S. and European regulators around orphan designation. And yes, they agree this is a large population and this mechanism of action could apply not just to Advanced Parkinson's disease, but to more moderate Parkinson's disease. So in this case we’re happy to say that we didn’t and we will not further pursue orphan designation.

[Sumant Kulkarni:]

Thanks.

[Operator:]

Thank you. I’m showing no further questions at this time. I will turn the call back over to Steve Paul for closing remarks.

[Steve Paul:]

Okay. Well, thank you and that concludes our call. We want to thank all of you for attending this morning and for your thoughtful questions. We look forward to updating you on our progress in the near future. Thanks so much.

[Operator:]

Ladies and gentlemen, this concludes today’s conference. Thanks for your participation. Have a wonderful day.