Voyager Therapeutics, Inc.

good afternoon and welcome to voyager therapeutics fourth quarter and year-end 2024 financial results conference call at this time all participants are in a listen-only mode there will be a question and answer session at the end of this call please note that today's call is being recorded a replay of today's call will be available on in the arrest investors section of the company website approximately two hours after the completion of this call i would now like to turn the call over to trista morrison Chief Corporate Affairs Officer at Voyager.

Good afternoon. We issued our fourth quarter and year-end 2024 financial results press release this afternoon. The press release and 10-K are available on our website. On today's call, Dr. Al Sandrock, our Chief Executive Officer, will briefly review key recent and upcoming milestones, and we will reserve most of our time for your Q&A. Joining us for Q&A are Dr. Toby Ferguson, our Chief Medical Officer, Dr. Todd Carter, our Chief Scientific Officer, and Dr. Nathan Jorgensen, our Chief Financial Officer. Before we get started, I would like to remind everyone that during this call, Voyager representatives may make forward-looking statements, as noted in slide two of today's deck. These statements are based on our current expectations and beliefs. They are subject to risks and uncertainties, and our actual results may differ materially. I encourage you to consult the risk factors discussed in our SEC filings, which are available on our website, for additional detail. Now, I will turn the call over to Al.

Good afternoon, everyone, and thank you for joining us. As Trista said, we plan to keep our remarks brief and prioritize your questions. On slide three, I want to remind you of why we're so excited about Voyager. Our pipeline includes four wholly owned and 13 partnered programs. We have already begun to generate clinical data, and we have multiple opportunities to generate more in the coming years. We are particularly excited about our two wholly owned programs targeting tau, which we view as the most important target in Alzheimer's disease. We also have two platforms to enable CNS delivery. I think most of you are familiar with our tracer capsid platform for IV delivered CNS targeted gene therapies. We're also generating data with our ALPL based non-viral shuttle. I am hopeful we will be able to share some of that data with you later this year. Finally, our partnerships have been a significant source of non-dilutive revenue for us. That's a big reason we are able to report $332 million in cash as of the end of 2024. And with $8.2 billion in potential future milestone payments, we believe partnerships will continue to contribute significantly to our bottom line. As I always say, we are open for additional business. We are always discussing new partnership opportunities. While we are building a multi-modality neurotherapeutics company here, I want to make a comment about gene therapy, which comprises much of our current pipeline. Despite continued setbacks in the field, it is possible to create a gene therapy that drives value for patients and investors. Zolgensma proves this. I want to emphasize that many of the foundational principles behind Zolgensma's technical and commercial success are principles Loiger also adheres to. This includes focusing on genetically validated targets in severe diseases with high unmet need. It also includes IV delivery, which we view as critical to commercial viability. We believe IV-delivered AAV capsids will be required to enable gene therapy in most CNS diseases, given the limitations of localized delivery. The potential of our IV capsids to efficiently deliver across the blood-brain barrier, not only in infants, is presumably why Novartis came to us for an SMA gene therapy partnership. I'm not going to belabor this point, but I do think it is important to differentiate Voyager's approach from the broader gene therapy field. On slide four, you can see our pipeline. I won't go into a lot of detail here, other than to point out that our SOD1 silencing gene therapy program did move back into the research stage, as we announced last month. The payload did not meet our target profile, and we are going to need to identify a new payload to advance that program. At the same time, I will note that VY1706, our tau silencing gene therapy, has moved forward into IND-enabling studies and is advancing toward IND in 2026. On slide five, I will note a few more quick highlights from the quarter and upcoming milestones to watch. I mentioned that BY1706, which was selected as a development candidate in Q4 2024, has now advanced into IND-enabling studies. We are really excited about the data from our three-month non-human primate studies, where we are seeing 50% to 73% knockdown of tau messenger RNA quite broadly across the brain. We have previewed a little of this data in our corporate deck on our website, and we will share more at the ADPD conference in April. Our anti-tau antibody, VY7523, performed well in a recently completed single ascending dose study. There were no serious adverse events, and we saw dose proportional pharmacokinetics, as well as a CSF to serum ratio of 0.3%, consistent with other monoclonal antibodies approved for the treatment of Alzheimer's disease. We initiated a multiple ascending dose study in Alzheimer's patients, and we expect initial tau PET data in the second half of 2026. Finally, I want to point out that in Q4 2024, UCB's propranamab demonstrated for the first time that an anti-tau antibody can impact tau accumulation in the human brain, and that this may correlate with clinical benefit. It's important to acknowledge The study didn't meet its primary endpoint of the CDR sum of boxes, but our team walked out of the CTAD meeting feeling better about our anti-Tau antibody than when we walked in. Looking forward, I think there are several opportunities this year for third-party data to continue to build excitement for Tau. Merck has antibody data expected in mid-2025. and I look forward to seeing what we learn at ADPD in April, AAIC in July, and CTAD in the fall. Okay, I promised I would keep it short. I just want to thank all of our employees for their hard work, especially pushing to achieve those end-of-year goals like getting the development candidate for the TAO silencing program, working on the BY7523 single ascending dose analyses, and initiating the multiple ascending dose study. With that, we will open the call for questions. Operator?