Tell us about the transition from being a VP at Biogen to becoming the CMO at Voyager.
The reason I came to Voyager Therapeutics was for the people, the science and the chance to do something transformative in neurology. Fundamentally, I care about trying to make therapies that make a recognizable difference in the lives of people with neurologic disease. In particular, I would hope that we can develop therapies where the people treated readily identify how they are better, which is easier said than done.
Biogen isn’t a huge company, but it isn’t a small company either. The main difference is in transitioning from an organization with many resources and many skill sets to a small organization with fewer resources and skill sets, but also a higher degree of responsibility. That increased responsibility for strategy and oversight while understanding you need to attempt to do something transformative mixed with the different skills and the need to fund the research through investors makes the overall dynamic of the company quite different. You have to reset your expectations and think about the core features you are trying to execute on.
What are the biggest differences between leading at a larger company and at a smaller company?
The way you get your job done is different. You first and foremost need to attract scientific, human and financial resources. The first real ingredient in considering any CMO role is that you should really be thoroughly convinced that you understand, support, and think that the science is meaningful. That makes the other parts of the job much easier.
I came to Voyager because I had a deep belief in their technology and their people. Particularly, the technology of getting things into the CNS in a more efficient way that solves a fundamental problem of CNS drug development. If that’s true, you can make a clear case to investors and top talent. As a CMO, you need to step back and think about how to get stuff done with a different set of tools and circumstances.
The first real ingredient in considering any CMO role is that you should really be thoroughly convinced that you understand, support, and think that the science is meaningful. That makes the other parts of the job much easier.
How do you approach clinical trials differently at a small biotech as opposed to at a bigger company?
At a big company, you integrate yourself into an existing infrastructure and way of doing things. In a smaller company, like when I came to Voyager, we didn’t have any clinical trial apparatus. You get to build something from the ground up in the way you see fit. The way I think about it is to assess what clear sets of skills we need to execute on these trials and what do we need to bring in-house and develop such that we can differentiate from others where we can use consultants and other companies outside of Voyager and find the right balance.
Fundamentally, at a small company, I think about building the leanest possible unit with differentiated skills to execute on studies with the hope of keeping most of it external such that we adjust our cost appropriately. I’m trying to build the best neurology clinical development team I can with enough skills in-house to design studies, and then the execution is largely done externally with CROs.
Can you speak to specific decisions you made?
You can work with a range of CROs in the clinical trial world. We chose to work with a CRO that has a deeper set of expertise in neurology rather than a CRO with broad expertise. That is key because they have direct connections with investigators and sites within our area. There are also different vendors and academic groups in terms of biomarkers, where you can choose to be more risk-forward. At Voyager, we’re trying to double down on biomarker-driven neurology drug development and so we are making choices there that are scientifically sound but also push the envelope.
You need to be rigorous in your evaluation of where the state of science is for each biomarker you consider. The rubric that I apply to a clinical trial is, “If I include this, will it aid my decision making about whether or not this drug works?”
What does biomarker-driven neurology drug development mean to you?
Historically, neurology drug development has been burdened by the need to use clinical tools to make decisions about whether your drug works. The problem is that this requires large, long trials and, in earlier development with smaller studies, you can get false positives and false negatives. Clinical decision-making tools in and of themselves aren't great decision making tools, particularly early in drug development.
We very much think about indications like Alzheimer’s and ALS that have a set of either imaging tools like TalPET in our Alzheimer’s studies or neurofilament for example in ALS or frataxin in Friedreich’s Ataxia where you can understand if you’re impacting the biology early by measuring fluids and looking at pictures of people's brains. It’s about using those tools early on to get an understanding if your drug is doing what it should be doing without having to use clinical tools. That's really important particularly from a small company's point of view because you can do that more accurately, quicker, and cheaper than if you use clinical tools and that decreases the scientific risk and decreases the financial risk, which for a small biotech is always important.
How do you think about simplicity versus complexity in clinical trial design?
Doing innovative biomarker-based clinical trial design does not mean everything in the kitchen sink. You need to be rigorous in your evaluation of where the state of science is for each biomarker you consider. The rubric that I apply to a clinical trial is, “If I include this, will it aid my decision making about whether or not this drug works?” The rubric asks if this is a decision-making tool that is scientifically validated enough on which I can base decisions about the future of this drug on? Honestly, that list gets pretty short pretty quick.
I think people are overly optimistic about the state of most biomarker tools and therefore they are susceptible to doing six or seven additional experiments within the context of a clinical study that in many cases isn’t warranted.
You also don’t need to evaluate every single biomarker in every single patient in the study. There are certain biomarkers you can look at in the highest dose group to support decision-making. Early stage studies are always a mixture of safety and dose exploration and trying to get clinical and biochemical signals. You don't have to do everything all the time and you can save yourself time and money if you think more economically.
Can you share any updates about Voyager’s various programs?
I’ll start with the Multiple Ascending Dose (MAD) and Single Ascending Dose (SAD) tau antibody VY 7523 program, which is our molecule that binds pathologic tau. The idea is that it’s designed to impede the spread of tau in the brain. We just completed the SAD study and a recent press release focuses on the point that we’ve got initial positive data in that study in healthy volunteers that shows that the antibody has good PK, is dose proportionate and appears safe with limited immunogenicity. We got nice CSF to brain penetration in that context with a ratio of 0.3, which is consistent with other CNS antibodies used for treatment of disease.
In the context of the strong preclinical data where we inhibited spread, the characteristics of the molecule – in particular its being raised to a certain particular C-triple epitope and binding of pathologic tau – you put all these together and we have a potential best-in-class tau antibody that we’re excited to announce we’re moving into a MAD study that’s initiated. Overall, we have a clinical team up and going, we’ve completed a SAD study and we’re moving to a MAD study and the data as we see it looks quite good to support progress.
if we can use the ALPL receptor to drive multiple therapeutics across the CNS, it could potentially broaden the scope and enable Voyager to be a neurogenetics company that effectively delivers therapeutics to the CNS in a way that enables us to develop transformational therapies.
What about the TRACER platform?
On the overall TRACER platform, the capsids transporting payloads across the BBB into the CNS, the main highlight to focus on is our VY1706 program. We did stop our SOD1 program. We had a cargo-related issue that caused the program to be stopped, and we are looking for additional cargos. In the same press release, there are comments on our VY 1706 Tau program, which has an IND in 2026, but we shared some nice data showing that in four different versions of the molecule, we had excellent tau knockdown across broad regions of the primate CNS, so we’re excited to move that program forward. We have opportunities, with our partner programs with FA and GBA and then the tau program, to really understand whether the capsids effectively knock down targets in the CNS in humans.
We’re also very excited about the concept of using ALPL and other receptors to effectively drive other therapeutic molecules across the BBB into the CNS. We are also considering the idea that because ALPL can bind a virus into the CNS it may well be able to do that for other non-virus entities. We’re looking broadly across other types of therapeutics to ask if ALPL can drive other things into the CNS. We think the answer is yes but it’s a bit early for us to be able to share any data. We look forward to doing that later this year. But if we can use the ALPL receptor to drive multiple therapeutics across the CNS, it could potentially broaden the scope and enable Voyager to be a neurogenetics company that effectively delivers therapeutics to the CNS in a way that enables us to develop transformational therapies.
How do you think about different approaches to getting across the BBB and achieving targeted drug delivery to the brain?
Getting things into the CNS is a fundamental issue of CNS development. Finding better ways to do it is critical. I’m very excited about the idea that receptor-driven interactions can drive things across the BBB in a way that we haven’t previously conceived. At Voyager, we’re focusing on ALPL because that’s a receptor we identified in ALS. We’re testing that to understand if it can get antibodies, oligos, proteins, enzymes and any therapy you can think of into the CNS.
There’s a lot of work with TFR as a ligand and that’s quite exciting as well. I think everyone has been quite excited by the TFR Trontinimab data showing that you can get beta amyloid into the brain at an increased rate with quicker reduction based on an amyloid PET signal. That data is quite compelling.
Fundamentally, this concept that you can exploit receptors is crucial to the field. I don't think we've yet fully come to understand the individual dynamics and characteristics of each of these receptors and when and if they should be used. The field is focused on TFR because that's what has been identified. There's a bit of other work from CD98 and a few other molecules, but fundamentally the field is largely focused on TFR. I'm quite excited to understand if there are alternatives to that potentially could be safer and or more effective. The concept of receptor driven delivery is critical and then trying to understand innovative ways beyond TFR to do that delivery is quite exciting.
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