Good day, and welcome to Voyager Therapeutics Second Quarter 2022 Conference Call. All participants are now in a listen-only mode. There will be a question-and-answer session at the end of this call which will be recorded. [Operator Instructions] I would now like to turn the call over to Julie Burek Vice President of Finance at Voyager.

Thank you, operator. Good afternoon, everyone, and welcome to this conference call to discuss our second quarter 2022 results and prioritized pipeline. A replay of today's call, including the Q&A, will be available on the Investors section of our website approximately two hours after completion of this call. After our prepared remarks, we will open the call for Q&A. As a reminder, various remarks that we make during this call about the Company's future expectations, plans and prospects constitute forward-looking statements for purposes of the safe harbor provisions under the Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including those discussed in the Risk Factors section of our most recent annual report on Form 10-K, which is on file with the SEC and as updated by our subsequent filings. In addition, any forward-looking statements represent our views only as of today and should not be relied upon as representing our views as of any subsequent date. Except as required by law, we specifically disclaim any obligation to update or revise any forward-looking statements even if our views change. I'm joined today by our Chief Executive Officer, Dr. Al Sandrock. For the Q&A portion of the call, we will be joined by our Senior Vice President of Research, Dr. Todd Carter. Now I will turn the call over to Al.

Thanks, Julie, and good afternoon, everyone. I'm extremely pleased to discuss some exciting new developments at Voyager. Voyager's mission is to pioneer the discovery of transformational AAV capsids that we hope will enable the development of life-changing gene therapies. We believe that the novel capsids derived from our proprietary tracer platform represent the breakthrough innovation that will address certain fundamental limitations that currently hamper gene therapy. We and our partners plan to leverage these capsids to advance the field of gene therapy for the central nervous system as well as other organs. We believe that our ongoing collaborations involving the TRACER capsids, including those recently signed with Pfizer and Novartis are progressing well. Both have option exercise milestones coming up in the next several quarters. Soon after joining the Company as CEO earlier this year, I led a comprehensive process to evaluate Voyager's R&D programs and determine where to focus with the goal of creating important new therapies for patients and growing shareholder value while maintaining our cash runway into 2024. Today, we are excited to announce our prioritized development pipeline, which that builds on advances we've made with our TRACER capsids. Gene therapy has the potential to transform the treatment of many serious CNS diseases. A clear example of this is the transformational impact that Zolgensma had for the treatment of infants with spinal muscular atrophy. However, the FDA label limits the use of Zolgensma to up to age two. The blood-brain barrier appears to preclude the use of intravenous gene therapy in older children and adults. Consequently, delivery methods such as the direct injection of gene therapy into the cerebral spinal fluid or CSF space or into the brain parenchyma have been and are being attempted. On Slide 5, we show examples from the published literature of what…

Thank you, Al. As we've previously announced, we have executed two important deals with Pfizer and Novartis, two global leaders in gene therapy for the application of our capsids for certain specific diseases. These deals have provided Voyager with meaningful nondilutive capital and have the potential results in substantial additional milestone and royalty-based revenue. We believe both the Pfizer and Novartis have been progressing well with our teams collaborating closely. Looking ahead, we anticipate the Pfizer option exercise decision by October 2022 and the Novartis option exercise decision by March 2023. I'd also note that Voyager has ongoing partnership with Neurocrine Biosciences on a preclinical Friedreich's ataxia program and two undisclosed discovery programs. We are optimistic about the potential to enter into additional TRACER capsid collaborations with the goal of further leveraging our TRACER technology in partnership with other pharma companies. And in doing so, potentially helping to bring important new medicines forward. I'll now turn to our financial results. In the interest of time, I'll focus on a few key metrics. Voyager is in a strong position as we advance our platform and portfolio forward. We reported cash, cash equivalents in marketable securities of $148.1 million as of June 30, 2022. Based upon our current operating plan, we expect that existing cash, cash equivalents and marketable securities will be sufficient to make planned operating expenses and capital expenditures into 2024. Please see our press release and SEC filings for further details on our financial results. I'll now pass the call to Al for concluding remarks.

Thank you, Julie. Before I get to my concluding remarks, I'd like to welcome Catherine Mackey to our Board at this pivotal time in Voyager's evolution. Catherine's outstanding track record of R&D success, coupled with her vast expertise and strategic collaborations with industry partners will be invaluable to Voyager as we advance our pipeline and maximize our TRACER capsid discovery platform. I joined Voyager because I'm optimistic about our ability to make a meaningful impact on the lives of patients. I believe that the potential of gene therapy is enormous, but the challenge of delivering these therapies safely and effectively to the central nervous system as well as other organ systems, has limited its utility to date. We believe -- I believe our novel TRACER capsids can address some of these limitations and provide an opportunity for us and our partners to advance differentiated programs toward the clinic. The demonstration that our TRACER capsids have improved target organ tropism across species, combined with the very recent identification of the receptor for one of our promising capsids and its human Humalog gives us additional optimism that our capsids will offer the potential for improved tropism in humans. Our ongoing collaborations are going well, and there are upcoming license option exercise states, including with Pfizer in October of this year. We're also optimistic about other potential collaborations in the future, given the promise offered by the novel capsids derived from TRACER across multiple disease areas. Our prioritized pipeline includes differentiated programs against validated targets for diseases of high unmet need, featuring strong preclinical pharmacology as well as clinical development plans with efficient paths to human proof of biology. We look forward to updating you about the progress on our science, our pipeline and our partnerships in the coming months. Thank you for listening. We'll now open it up for questions.

[Operator Instructions] The first question comes from Jack Allen with Baird.

Congratulations on all the progress in the prioritization of the pipeline. Maybe first, at a very high level. I was hoping you could provide some more context around the three assets that you plan to move forward. Maybe characterize the derisked nature of each of the assets and maybe the riskiness of put another way of each of the assets. And then I have a follow-up as well.

Jack, this is Al. Thanks for the question. I'm not sure I heard the first something that nature. I know I heard the risky nature, but what was the first part of that?

Just said another way, how de-risk maybe view each of these candidates if you could think about the overall risk profile of each of the assets would be good.

Yes. No, thanks. Yes. No, it's, look, these are high risk, high reward, right? I mean, because they're, we tackle diseases with high unmet need. But we feel we can manage the risk because we chose programs deliberately where we could de-risk early in clinical development and efficiently. So for example, in the case of the tau program, we feel we can use helped imaging to see whether or not we can block the spread of tau in a very efficient manner in an early phase clinical trial, perhaps even in a Phase Ib trial in a matter of, say, 12 months. And in the case of SOD1 ALS, for example, we can measure CSF SOD1 levels to make sure we're silencing or reducing the expression of and that we can also look at plasma neurofilament as a way of assessing whether or not we're decreasing the degeneration of spinal motor neurons as well as brain motor neurons. So I think it's important to realize that one of the key criteria we use in selecting these programs that we can efficiently derisk, if you will, and gain proof of biology and proof of concept.

Great. Great. And then just a follow-up. I know that the SOD1 ALS program does have an asset under regulatory review to [indiscernible] from Biogen. I'll speak to the results you've seen from that asset to date and any confidence that gives as you move towards the clinic with your asset and how it could impact the treatment landscape moving forward as well?

Well, everything I've seen is based on public information. And from what I see, if we use baseline neurofilament as a covariant as presented at the recent NCA meeting that there is efficacy on several important clinical outcome measures, including the functional rating scale. So I think that -- and then there are, I mean, there are certainly reports of patients who are -- have a very long extensions of survival. So those are more in the anecdotal reports, but I remember seeing a report on CBS morning news of the patient who's still playing golf or several years. And so -- which I think is pretty remarkable. So anyway -- so I, look, I think a lot more, I look forward to seeing more data, particularly as the file. I guess, they've now filed it. Are they going to file for approval and the PDUFA date, I believe, is next January. So I expect to see much more data. And of course, by the time we get into the clinic, we'll see a lot more data from the FDA briefing documents and other documents in the public domain. So we'll learn a lot from that, and we'll leverage whatever information we get and incorporated into our clinical development plan.

Next question comes from Divya Rao with Cowen & Company.

This is Divya on for Phil. Congrats on the quarter and the exciting pipeline update. Just, two questions from us. One, based on just Voyager's previous clinical data, especially in Parkinson's disease, do you see any overlap in the current pipeline programs? Obviously, other like in terms of the actual candidate that you're selecting that would potentially enable rapid entry and progression through the clinic. And then just like a more, I guess, specific question, the limitations with AB, especially when delivered systemically, is the increased liver accumulation. I was wondering if you had any comments on what you're seeing in terms of liver accumulation with these captives either in rodents or the nonhuman primates.

Thanks, Divya. Those are great questions. First of all, in terms of overlap, the previous Parkinson's program, which was actually terminated last year, and it was a partnership with Neurocrine was a different payload. It was actually delivering AADC aromatic l-amino acid decarboxylase and it was actually using intraparenchymal -- convection-enhanced intraparenchymal delivery. And so our program is very different. We plan to go with IV-delivered TRACER capsids. So different capsid, different route of administration, different payloads. Here, we're going to -- the payload GCase, the enzyme that is encoded by the GBA. And ours is more of a disease-modifying approach, if you will. And so not too much overlap, I would say, but with the last, with the program that was terminated now. I don't know, Todd has anything to add before I jump to the next part of the question on liver.

No, I think you captured it. I think importantly, the goal of doing something that could be disease modified, is this true.

And then in terms of the liver, that's a great question. I think that one of the reasons why we're excited about the TRACER capsid is that not only do they increase tropism into the desired organs like the CNS, but many of them show at the same time, detargeting organs like the liver where we get toxicity. That's -- so that's very promising. And then the second thing is that since they're so potent at getting into the brain with IV delivery, we hope to be able to use lower doses. And in fact, we're going to be showing data and Todd, I'm sure, knows much more about this, we're doing dose range finding studies, but to show that we can go to lower doses, which should also help with the liver toxicity issues. Todd.

Yes. So Al, you captured it. It is a great question. I think the whole field has seen toxicities in the DRGs and in the liver. And what we're seeing with our capsid, as Al pointed out, is we identify those capsids that deliver into the brain while detargeting the liver and DRG and potentially other regions as well. So it's one of the things that we are finding most telling about the taxes in addition to that enhanced BBB penetration that would allow a lower dose.

[Operator Instructions] The next question comes from Yung Zhong with BTIG.

So the first one on the technology platform. Do you have a sense your expectation the dose level that you will be issued achieve sufficient maybe exposure in the brain? And sorry, have you looked at immunogenicity because oftentimes when with novel capsids, I believe we have seen a lot of unwanted immune response.

I'm going to start to answer these questions. Thanks for the great question.

Excellent questions. Thank you. With the dose levels, what we're seeing, we reported this at prior year ASGCT the team therapy conferences that we're able to get substantially better delivery. So 100-plus-fold better delivery into the brain versus what's currently the state-of-art AAV9, so what we're anticipating is the 10 fold or better improvement or lowering of the dose we hope to achieve and that we're seeing evidence that we can. We're anticipating some additional reports on this upcoming key therapy conferences that I referenced earlier. On the immunogenicity side, so by and large, we're making specific to these capsids. We're targeting particular loops that we've identified that we can modify without causing problems with the capsid. And by and large, those do not impact the immunogenicity that we've seen. So preexisting immunity so far is very similar to the parental capsid. We have not identified any increased immunogenicity up to now.

Okay. So if I can ask a question about indication, I know with your experience with Alzheimer's and with company's experience with Parkinson's is reasonable. But given the complexity of the pathophysiology behind those diseases, what's your comfort level that you will be able to use a gene therapy approach to target those very complicated neurodegenerative diseases? And I think, yes, that's the question.

Yes. Well, let me start and Todd could also answer. I believe that by targeting the -- we chose targets that are highly validated. And in the case of PD, for example, we're going to start with the subset of patients that have GBA, that are GBA carriers. It's still -- it's a pretty large subset as we set up to 10%. Some papers say, 5%, some say 10%, but up to 10% of Parkinson's patients have GBA1 mutation, the most common genetic risk factor. So I think it is a complex disease. But I think if by targeting that very large subset of patients who are GBA carriers, I think that we reduced the complexity, if you will. We also can measure whether or not we've replaced the enzyme again, another de-risking maneuver that we can do early in clinical development. We can see whether or not we've replaced the enzyme and gotten a normal expression or at least getting toward normal expression of the enzyme by looking at cerebrospinal levels. And so -- and then also in the case of Alzheimer's disease, that was the other part of your question. Again, I think tau is a pretty darn well validated target. As I mentioned earlier, in some ways, the progression of tau is better correlated with dementia than any other biomarker, and again, the ability to image tau, I think, greatly, and also a manager of phosphorylated tau or pathologic forms of tau in the CSF and blood really help us de-risk the program. So I'm pretty optimistic not only about our ability to do therapeutics in these diseases, but I think the whole field has learned a lot, and we're going after well-validated targets using modern measurement tools. So I'm actually very optimistic

This concludes our question-and-answer session and Voyager Therapeutics second quarter 2022 conference call. Thank you for attending today's presentation. You may now disconnect.