Good morning, and welcome to Voyager Therapeutics Fourth Quarter and Full Year 2021 Conference Call. [Operator Instructions] Please be advised this call is being recorded at the company's request. I would now like to turn the call over to Julie Burek, Vice President of Finance at Voyager.

Thank you, operator. Good morning, everyone, and welcome to this conference call to discuss our most recent license option agreement and to review our fourth quarter and full year 2021 results, both announced this morning. A replay of today's call will be available on the Investors section of our website approximately 2 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 these 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 members of Voyager's leadership team, including our interim Chief Executive Officer, Michael Higgins; our Chief Business Officer, Allen Nunnally; and our interim Chief Scientific Officer, Glenn Pierce. Board Director, Al Sandrock; and Chief Operating Officer, Robin Swartz, will also join the Q&A portion of the call. Now I will turn the call over to Michael.

Thanks, Julie, and good morning, everyone. I'm extremely pleased to share that earlier this morning, we announced a license option agreement with Novartis for target specific access to our proprietary tracer AAV capsids. This transaction is the second major licensing agreement around our novel capsids in the last 5 months, and provides Novartis with access to our novel AAV capsids and options to license our capsids for potential use with 3 undisclosed CNS targets plus options to access capsids for 2 additional targets to be determined in the future. The transaction further validates the potential of our tracer capsid discovery platform to broadly enable a new wave of AAV gene therapies across the field and across our internal pipeline. It's also complementary to our agreement with Pfizer announced last October. That transaction provided Pfizer with target specific access and option rights to our tracer capsids for exclusive use with one CNS target and one cardiovascular target. Together, these major transactions reinforce our corporate strategy to pursue internal and external applications of our TRACER platform. Importantly, the targets and transgenes involved in the Novartis and Pfizer collaborations are distinct from those planned for our internal pipeline. Outside of these agreements, we continue to retain global rights to our tracer AAV capsid platform, as well as all capsids arising from its use with other targets. We believe there is considerable potential for future business development opportunities around the TRACER platform, given the focused nature of the deals we've done to date as well as our expanding and maturing capsid library. We view these agreements as critical validation for the potential of the tracer capsid discovery platform to enable gene therapies that may target desired cells and tissues with greater specificity at lower doses and with fewer off-target risks than conventional AAV serotypes.…

Thank you, Michael. This is an exciting time for Voyager. Our agreements with Novartis and Pfizer substantially expand the number of therapeutic programs in which our proprietary capsids may be deployed and highlight the potential of our TRACER platform to generate future business development opportunities, particularly as our novel capsid library expands within and beyond the CNS and initial tracer derived capsids are further refined. Moreover, these agreements have generated $84 million of aggregate upfront payments that substantially strengthen our balance sheet. I'd like to provide an overview of the license option agreement with Novartis we just announced. Novartis may exercise options to license novel AAV capsids generated from Voyager's TRACER capsid discovery platform for potential use with 3 undisclosed CNS targets, and options to access capsids for 2 additional targets to be agreed on in the future. Voyager will receive $54 million upfront and is entitled to receive up to $37.5 million in exercise fees for options for the 3 initial CNS targets exercisable by Novartis within 12 months of signing. In addition, Novartis may elect to evaluate capsids for up to 2 additional targets to be agreed in the future, subject to their availability for $18 million upon selection of each target and the $12.5 million exercise fee for selection of the capsid for each target. Voyager will also be eligible to earn up to $1.5 billion in potential development, regulatory and commercial milestones for products utilizing Voyager license capsid as well as mid- to high single-digit tiered royalties based on net sales of Novartis products incorporating the licensed capsids. The targets for which Novartis will receive rights under the agreement, will be distinct from those planned for Voyager's internal pipeline. We retain global rights to all licensed capsids for use with other targets and to all other…

Thank you, Allen. We have oriented Voyager to address some of the most critical challenges facing gene therapy, potentially unlocking the tremendous opportunity this modality holds to help patients. With first-generation AAV gene therapies, tissue-specific targeting is typically suboptimal, and the therapeutic index is often poor. As a result, many developers have encountered major toxicity issues if they dose high enough to achieve efficacious levels, with toxicity limiting the potential for optimal efficacy in many cases. In fact, a recent analysis revealed that clinical trials evaluating cell and gene therapies accounted for approximately 40% of all clinical holds in 2021. The ability to produce capsids capable of delivering a payload to specific tissues, whether that is for CNS or cardiac tissue or other parts of the body with limited exposure elsewhere is critical to the success of AAV gene therapy. We believe that Voyager has developed a core technology with our TRACER capsid platform that may enable meaningful therapeutic benefit for patients. TRACER allows us to evaluate millions of different possible modifications to existing AAV capsids, and select only those capsids to display increased transduction in specific tissues or cells. This approach takes advantage of 2 distinct methods that historically have not been used by others in this field. The first is to perform this initial screening, along with a series of subsequent screens in nonhuman primates, so that we're selecting for capsids that show enhancements in a species very closely related to humans, not those that have only shown activity in mice, which often don't translate well into human beings. Second, we measure the performance of our capsids at each step of the screening process by evaluating the expression level of messenger RNA or mRNA. In order to produce mRNA an AAV vector directed to a CNS target must…

Thank you, Glenn. In light of the time we have devoted to today's exciting news and the time remaining, I'll limit and focus my remarks this morning on our cash position and how our transaction with Novartis extends our runway. Please refer to our press release and 10-K issued earlier today for details of our financial results for the fourth quarter and full year of 2021. Voyager is in a strong financial position as we advance our platform and portfolio forward. Our cash, cash equivalents and marketable securities as of December 31, 2021, were $132.5 million. This does not include the $54 million upfront payment, we are entitled to receive from Novartis under the recently announced license option agreement. With the upfront payments from our Novartis and Pfizer agreement, our cash runway now extends into 2024, enabling the company to achieve potential further advances in our tracer platform development and pipeline program. With that, I will hand it back to Michael.

Thank you, Julie. We've made tremendous progress since we announced the strategic shift for Voyager about 9 months ago to focus on maximizing the opportunities created by our TRACER platform and realigning our pipeline to deploy this next-generation technology. We've published very exciting data on some of our first TRACER capsids and look forward to presenting more. Our licensing agreements with leading gene therapy companies provide additional validation for the value of our platform, and we've enhanced our leadership team with highly accomplished executives. Looking to the spring, we have several goals we're working towards. We expect to release additional data on our capsid discovery campaigns. We've already disclosed some promising data on AAV5-based capsids and capsids targeting glial cells, and we look forward to building on that. On the therapeutic pipeline side, we're continuing to progress our programs toward IND-enabling studies and expect to release further preclinical data in the coming months. We're also optimistic about the potential for additional BD transactions anchored by the growing potential of our capsids and therapeutic programs. I've never been more enthusiastic about the potential of our technology and of our company to make a meaningful and positive impact on the lives of patients. The range of diseases that could potentially be addressed with gene therapy is vast. But is often limited by the field's ability to deliver these therapies safely and effectively to the right organs and tissues. We believe our TRACER technology offers great promise to overcome these limitations and help unlock the potential of AAV gene therapies. With that, we thank you for your interest and support, and we'll open it up to Q&A.

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

Great. And congratulations to the team on all the progress. I guess the first question I had was on the Pfizer partnership? And any additional color you could provide with regard to how that's going to date. Have you delivered any of the, I guess, necessary constructs to Pfizer with regard to the first 2 transgenes and any qualitative comments you can make on that partnership would be great. And then I have a few follow-ups as well.

It's Michael. Thanks very much for the question. I think Allen can dive into that one first.

Thanks a lot for the question, Jack. So as you know, from the first deal with Pfizer, there's a 12-month evaluation period during which we provide the constructs necessary for Pfizer to evaluate the capsids, so that's underway, it's in process. They let us know which capsids they'd like to evaluate right now, and that work is ongoing. So we'll find out whether and which capsids they like to exercise on. They have until October of this year to make that decision.

Got it. Great. And then on the Novartis program, I was hoping you could provide some insights with regard to some of the color around the CNS indications that Novartis is looking at and the relative size of those opportunities? And then just my last brief question was how to think about Voyager's advancement of the internal pipeline and when we might see an internal product move towards the clinic. I know you outlined that there's going to be some preclinical data this spring, but any guidance with regard to movement towards the clinic would be great.

Sure, Jack. So I'll take the first part of that and then hand it over to Glenn. So the CNS indications, the 3 CNS targets under the Novartis deal are undisclosed. So we can't comment on what those are, except that they are in the CNS. So there is a focus on rare diseases in CNS just in terms of the limitations of the agreement that will be disclosed in due course, but it's not really very limiting when we talk about what rare disease is with respect to CNS. But maybe I'll pass it over to Glenn for the second part of your question.

Thanks, Allen. Jack, this is Glenn. With regard to the pipeline, it's an early stage pipeline. We rebooted last August and really began to focus the pipeline entirely on the tracer capsids. So this means intravenous delivery for a number of the targets, including the CNS targets that we have in the pipeline. We have not released any time lines at this point. But suffice to say, it's early stage. We are developing the capsids. We're developing the production processes and doing the requisite preclinical work to move those into the clinic.

Congratulations again on the progress.

Our next question comes from Laura Chico with Wedbush Securities.

I guess I have one question with regards to, I guess, the overall strategy for Voyager. Could you talk a little bit about kind of the balance between the internal pipeline efforts and more of the business development strategies. I guess looking ahead, over the next few years, how should we be thinking about kind of the balance between these 2 dynamics? And is one, a greater priority than the other? And then I have one quick follow-up.

Thanks for the question, Laura. It's Michael. Let me take that first, and then the team can weigh in if they have any other pieces to add. But -- the -- obviously, both elements are critically important. And ultimately, we're all about delivering products to patients and providing them benefit. The strategy we followed thus far is to take full advantage of the great work that the team has done with the TRACER platform. So we have focused early on, on getting out the capsids to some other major players in the field to allow those programs to move forward. But we remain a therapeutic company and we are prepared to move forward. We have made a big shift in our pipeline, as Glenn just mentioned, and there's work to be done there. But you should expect that we'll continue to move forward our own proprietary pipeline, and we'll continue to do transactions. Allen, you can talk a little more about kind of the types of transactions people might expect over the coming years.

Sure. Happy to. Thanks, Laura. So the -- there really is every possibility of continued business development. There are a lot of targets out there, both within the CNS and especially as we consider beyond the CNS. So there's plenty of opportunity for Voyager to have its own program prosecuting and also to help enable other partners in the programs that they are working on. We're not going to prosecute every target in CNS, no company is going to do that, let alone in the broader field beyond the CNS. So I think there's one possible future opportunity in the business development side there as well as the traditional collaboration where we work on programs together with partners. We've done some of that in the past, and that's something we'll continue to explore as we move forward here.

And Laura, one additional comment is probably quite clear is these early transactions, in light of kind of the market challenges that are out there and the need for capital for an organization in our stage, these early transactions are also quite helpful in us kind of strengthening the balance sheet and allowing us to make these investments and kind of move the company forward. So they have a dual benefit in that they ultimately, we hope, will provide significant benefit to patients, but in the near term, may help us to execute on our overall strategy.

That's helpful, Michael. Maybe one quick follow-up then. So obviously, Voyager has been involved in clinical trials previously with prior programs. I'm just curious, I think it was Glenn that made a comment kind of about the regulatory hurdles that some of the sector have faced. As you're moving towards clinical efforts with TRACER, I'm curious what additional resources do you need to have on board? Or are there certain gating factors outside kind of accumulation of preclinical work that needs to occur before you can get to the clinic?

Laurie, this is Glenn. I don't think there are particular specific gating factors other than the normal gating factors required for putting in AAV gene therapy product into the clinic, which does have to follow a specific pathway based upon safety and efficacy. With regard to the novel capsids, those functions like the conventional AAVs, they just have different tropism and will provide a safety profile that we are anticipating based upon the preclinical work that we've done. It should be substantially different than the safety profile that's being offered by the conventional AAVs. And so what that means is that while we will need to be on high alert for any safety issues as everyone is with the conventional AAVs, we're anticipating a much broader therapeutic window with these capsids because they've been designed to offer that.

Our next question comes from [Divya Rao with Cowen and Company].

This is [Divya], on for Phil. Congrats on the Novartis deal and the exciting progress. We just had a question on if there were any updates in securing a partner for the VY-AADC clinical program. And also if there were any -- if there was any additional progress that has been made in addressing some of those imaging and clinical assessment concerns that the DSMB had?

So let me just take a quick -- give you a quick response, and then we'll let Glenn give a little more detail on it. So we haven't provided any updates with regard to the discussions or the progress around the program. We have obviously, as you know, the program was put on hold some time ago, and that has remained in that position and I believe that there are significant challenges in terms of the technical aspects of that. So we don't expect to be providing significant updates on that program at this time.

Yes, this is Glenn. The clinical work that we did with Parkinson's as well as the preclinical work with Huntington's disease, both involved intraparenchymal delivery of AAV. We are of the opinion at this point that is not necessarily a good idea, based upon our collective experiences there. And that is the reason why the TRACER platform offers us so much potential, the ability to dose intravenously, get across the blood brain barrier in sufficient quantities to offer a therapeutic effect. So we have switched our entire path pipeline and planning over to intravenous delivery of these capsids for CNS diseases as well as for non-CNS diseases.

Our next question comes from Yanan Zhu with Wells Fargo.

And congrats on the Novartis deal. First, a couple of questions regarding that deal. This partnership seems to have higher economics compared with the Pfizer deal on a per target basis. Could you comment on why that is the case? And have you had additional validation, additional data since the Pfizer deal? And also for the 3 targets, do you expect to deliver 3 different capsids or could it be the same -- one same target -- sorry, one same capsid for all 3 targets?

Yes. So thank you very much for the question. Indeed, you've correctly noted that the per target economics are increased in the Novartis deal relative to the Pfizer deal. Of course, every business development negotiation is different. But to your second point about what may be behind that, we have, of course, progressed our work on the capsids. And our partner, Novartis had the most up-to-date information that was available as we negotiate that deal. And I think that the terms speak for themselves with regard to what we were able to achieve there. There is one difference between the 2 deals is that the 3 initial targets with Novartis are all CNS in the prior deal with Pfizer, there's 1 CNS target and one cardiovascular target. So obviously, there are always differences between any 2 deals and any 2 partners. So -- but there has been progress in the work and the most up-to-date information is provided to our partners in our negotiations and discussions. And I think there's one more part to your question, I'm sorry.

Right. For the 3 targets in the Novartis deal, are you expecting to deliver 3 different capsids? Or could it be on 1 capsid?

Yes. So it really could be either. We do think there's a reasonable hypothesis that some of our capsids, some of our best capsids maybe workhorses that can be applicable for multiple targets. In fact, it may be the case that Voyager uses one capsid for one or more of its own pipeline programs and one or more of our partners might end up using the same capsid for some of theirs. It's equally possible, however, that a partner like Novartis may select 3 different capsids for 3 different CNS indications. It is important, obviously, to target the cells that you're after specifically. There -- we've shown data for neurotropic capsids as well as those that have glial-tropism. Those can be important, and it really depends on what the indications are. But -- we want the capsids to be fit for purpose, and those purposes will depend on what the target is.

That's very helpful. And then maybe one question on the platform, from a safety perspective for systemically delivered AAV gene therapies, I think liver toxicity as well as complement activation are some of the issues that other programs in the field have had. Given that you have increased tropism for the CNS, could you talk about the relative increase compared with liver tropism or in terms of complement activation, what is the relative reduction of exposure to -- in those aspects?

This is Glenn. It depends upon the capsid, but in general, these TRACER capsids are offering 2 possibilities to increase the therapeutic window. The first possibility is that we can simply use a lower dose of the capsid, substantially lower dose. And by doing that, we are providing a lower dose to the organs that are -- and tissues that are subject to the toxicity. The second aspect of this is that we have noticed in some of our TRACER capsids that they are detargeting specific organs. For instance, we've got a capsid that is detargeting the dorsal root ganglia, we have a capsid that is detargeting the liver. And so by pulling those 2 levers, decreased dose versus detargeting and using them either separately or in combination. We think that expanding that therapeutic window in both directions will offer us some safety advantages over the conventional capsids that don't have much of the therapeutic window.

Great. Thanks very much for the helpful information.

[Operator Instructions] Our next question comes from Sumant Kulkarni with Canaccord.

Nice to see all the progress. Welcome to Dr. Sandrock and congrats to Robin on the promotion. I have a few questions here. So one of your slides shows manyfold expression for TRACER capsids versus more traditional AAV9. Given this knowledge and the different expressions in various parts of the brain, are there any specific portions of the brain you would like to keep for yourselves?

That's an interesting way to phrase that question. There is -- these capsids do have differential tropism for different regions -- different structures within the brand. So you're absolutely correct about that. In terms of keeping anything to ourselves, we've identified a pipeline that we are interested in. In that pipeline, we're continuing to make progress forward on. As you know, there are a lot of diseases -- both logical diseases as well as other diseases that have been approached with AAV therapies that continue to have serious unmet needs. So our thinking really is that if we can get these capsids in combination with our programs, but more importantly, in company with our partners, to patients that have these diseases then everyone benefits. And that's really the key.

And then from a strategic point of view, you've done a commendable job on refocusing our strategy now with 2 external partnerships. But there are 2 very important positions in management that are still on an interim basis. What are your plans to remove that interim status?

Yes. So thanks for the question. Glenn and I do remain on board as interim leaders working closely with the management team. And our view is the following: We are committed to the company and committed to help us move forward. We have conducted and continue to conduct this [Technical Difficulty], and we feel like we can attract the really strong candidates. With this, there is validation of the work that we're doing here, and we think that will further help our efforts but we're holding up a high bar make sure we get the right [codes] that can help us create the value in the future. So we're confident we will get good individuals, and we're feeling good about that. But we're taking the time to make sure it goes well. We're also making sure Glenn and I are working closely with the team. So we have the capabilities we need right now, and we feel like we're executing. And we're going to keep the bar high and get the best candidates possible.

I'm showing no further questions in queue at this time. I'd like to turn the call back to Michael Higgins for closing remarks.

Okay. Well, thank you, everyone, for your attention and for you our interest in Voyager. We're really excited about the -- not only the transaction that we announced this morning, but particularly excited about the future. We feel like we've made some nice progress over the last months, and we're looking forward to keeping you up to date as we continue to move the business forward. So thanks, and we will stay in touch, and please reach out to us if you have any follow-up questions in the future. Have a great day. Take care.

Ladies and gentlemen, this concludes today's presentation. Thank you once again for your participation. You may now disconnect.