The Biology Will Win
What I Saw in Baltimore at HIPE
Disclosure: This post reflects my personal experience attending the Help4HD HIPE Conference in Baltimore on April 25, 2026. Nothing in this post constitutes investment advice, and as always, my track record and position history are publicly timestamped on X.
I flew to Washington D.C. on Friday (and drove to Baltimore on Saturday) with a thesis. I left with something harder to quantify, not a different thesis exactly, but a materially deeper understanding of the terrain on which this thesis will ultimately be resolved, and a set of experiences that I think are worth documenting carefully, both for subscribers who are following AMT-130 and for anyone who wants to understand what is actually at stake in this regulatory fight.
When you spend most of your time analyzing a disease through the lens of financial models, regulatory filings, clinical trial data, and competitive landscape assessments, it is genuinely easy to keep the human reality of that disease at an intellectual remove. The biology becomes an abstract puzzle to be worked through. The FDA becomes an institutional adversary to be gamed or outmaneuvered. The patient population becomes, in the language of biopharma analysis, a “market” to be sized, with addressable populations and pricing assumptions and peak sales estimates. I have done all of this analysis with AMT-130, and I believe it is rigorous and important — but what the Help4HD HIPE conference in Baltimore did was strip away every abstraction and replace it with something unmediated: the actual human reality of Huntington’s disease, in a room, looking back at me.
I want to try to describe what that was like, because I think it matters to how you understand everything else I am going to say in this post.
The Room
The conference was held in a hotel ballroom — round tables, a raised stage, the standard infrastructure of a professional gathering that you have been in a hundred times for a hundred different purposes. However, the population of people in that room bore no resemblance to any professional gathering I have attended. Coming to this conference as an investor, even one who has spent considerable time immersed in the clinical and scientific literature on Huntington’s disease, did not prepare me for what I encountered when I actually started meeting and talking with the people there.
I met people who carry the pre-symptomatic gene for Huntington’s disease — people who have tested positive, who know with genetic certainty what is coming for them, and who are now living in that strange suspended reality of watching for the first signs while hoping that the pace of scientific progress outpaces the pace of their own biology. The psychological weight of that position is difficult to describe. These are people who made a decision to know — a decision that is itself enormously consequential and personal — and who are now navigating a life organized around a diagnosis that has not yet fully manifested. Many of them are deeply engaged in the advocacy and research ecosystem precisely because that engagement gives them agency in a situation that otherwise offers very little.
I met families who have already lost a parent to Huntington’s disease. They watched that parent deteriorate, watched the disease move through its stages, the cognitive changes, the physical decline, the caregiving demands, the grief of losing someone incrementally before losing them completely, and now they are in the position of having a child who has tested positive. The simultaneous weight of that grief and that forward-looking terror is not something you can fully appreciate from the outside. These are people who know exactly what the disease does, in the most intimate possible way, and who are fighting for their children with the urgency that knowledge produces.
I met people in the advanced stages of Huntington’s disease themselves — in wheelchairs, struggling with the chorea that makes controlled movement so difficult, struggling with eating, with communication, attended by caregivers whose love for them was visible and uncomplicated. These were the people who made the room feel most real to me, and I say that meaning no disrespect to any of the others, because their reality was equally real. However, there is something about seeing a disease in its advanced stages — not in a clinical photograph, not in a medical description, but in a person sitting three tables away from you in a hotel ballroom — that reorganizes your understanding of what it means for a regulatory agency to delay or obstruct access to a treatment that might have slowed its progression.
Near the front of the stage, a service dog slept quietly on the carpet throughout the morning sessions. I took a photograph of it. I find it difficult to fully articulate why that image stayed with me, except that it seemed to capture something true about the texture of the day: the presence of something steady and devoted and undemanding in a room full of people who carry an enormous amount.
[Photo: Service dog resting near the stage at the Help4HD HIPE Conference, Baltimore]
A film crew from Stories Productions was present and documenting the entire conference. The documentary they are producing is specifically framed around what the FDA has done to the Huntington’s disease patient community — the human cost of a regulatory process that has, in the view of virtually everyone I spoke with, ceased to function in good faith on this particular question. I don’t have a release timeline for the documentary, but based on the footage they would have had access to in that room, I expect it to be important and difficult to watch in equal measure.
The Sponsors and What Their Presence Tells You
Before I get to the advocates and the conversations I had throughout the day, I want to linger on the sponsor slide that opened the conference, because I think it tells an instructive story about where the HD drug development ecosystem sits right now — and about how the industry as a whole is reading what happened to AMT-130.
[Photo: Help4HD Baltimore 2026 sponsor slide — uniQure, Teva, Novartis, Neurocrine Biosciences, Genentech, Wave Life Sciences, Prilenia, Griffin Foundation]
The roster of companies sponsoring a patient advocacy conference for a rare, ultra-orphan neurological disease is itself meaningful. Teva was there. Novartis was there. Neurocrine Biosciences was there. Genentech (a Roche subsidiary with one of the most sophisticated neuroscience research operations in the world) was there. Wave Life Sciences was there. Prilenia was there. These are not companies that show up to patient conferences for optics. They show up because they have programs in this space, because they are trying to understand the patient community they are ultimately working to serve, and because the regulatory environment for those programs matters enormously to their own development strategies.
Teva had brochures present for Austedo XR (deutetrabenazine extended-release) which is one of the only FDA-approved treatments for chorea associated with Huntington’s disease. It is worth pausing on what Austedo XR actually is and is not, because the honest accounting of the current standard of care in HD is directly relevant to understanding what is at stake with AMT-130. Austedo XR manages the involuntary movements that are one of the disease’s most visible and physically debilitating symptoms. It does not modify the disease and does not slow progression. It does not address the cognitive or psychiatric dimensions of HD. The language in Teva’s own materials is precise on this point: Austedo XR does not cure the cause of the involuntary movements and does not treat other symptoms of Huntington’s disease, such as problems with thinking or emotions. What Teva is offering is a symptom management tool in a disease that, in the complete absence of any disease-modifying intervention, moves in one direction and ends in one way. That is the current standard of care. That is what patients have access to right now. Keeping that reality clearly in view is essential to understanding the moral weight of what it means to obstruct access to something that might actually change the trajectory of the disease itself.
[Photo: Teva Austedo XR patient support brochure]
Novartis was present with materials on INVEST-HD, their Phase 3 clinical study of an oral investigational medicine designed to slow the progression of Huntington’s disease rather than merely manage its symptoms. The study is enrolling approximately 770 participants who are aged between 21 and 70, carry a gene-positive test result confirming HD with a CAG repeat length of 40 or above, and are in the early stages of the disease, which is to say, people with mild or as-yet-unnoticeable symptoms. This is the stage of the disease where a disease-modifying intervention has the greatest theoretical opportunity to be protective, which is precisely the same reasoning that underlies AMT-130’s target population and the TFC 9-13 eligibility window that has been central to the regulatory and clinical discussion around uniQure’s program.
[Photo: Novartis INVEST-HD Phase 3 study recruitment brochure]
Before I get to the Novartis team’s reaction to what happened with uniQure, I want to address something directly, because I suspect some readers will look at the INVEST-HD program and interpret it as evidence that AMT-130 is not uniquely necessary — that there are other shots on goal in HD, and that the regulatory obstruction of one program is therefore less catastrophic than it might otherwise appear. That reading is wrong, and it is wrong for reasons that are grounded in the biology rather than in competitive cheerleading.
INVEST-HD is an oral, systemic therapy. AMT-130 is an intracranially delivered gene therapy that acts directly at the striatum — the region of the brain where the pathological process of Huntington’s disease is most concentrated and most devastating. These are not substitutable interventions. They are operating through different mechanisms, at different anatomical targets, with different implications for the disease process. The exon1 HTT fragment — which the scientific literature increasingly identifies as among the most pathologically significant species in HD, and which is the target that AMT-130’s mechanism is best positioned to address — is not going to be reached in the same way by an oral molecule distributing through systemic circulation as by a therapy delivered directly to the site of pathology. An oral drug that achieves meaningful peripheral HTT lowering may turn out to be a genuinely useful intervention, and I hope it is, but it is not doing the same thing and it is not reaching the same target. Huntington’s disease is, at its core, a disease of what is happening in the brain, and there is a serious scientific argument (one that I find compelling) that it cannot be truly solved without going directly to the root of the problem at the striatum. The existence of INVEST-HD does not dilute the case for AMT-130. If anything, it reflects the seriousness of the disease — the recognition that it may require multiple complementary approaches operating at different levels — and the two programs are better understood as additive than as competitive. Framing them as alternatives, in the context of arguing that AMT-130’s obstruction is therefore less urgent, gets the science backwards.
The more useful analogy for how the HD treatment landscape might actually evolve over time (and this is something that emerged from conversations with people from multiple companies at this conference, not just my own extrapolation) is HIV. What the HIV treatment revolution looked like, once it arrived, was not a single curative intervention that rendered everything else redundant. It was a combination regimen: drugs operating through different mechanisms, at different points in the viral lifecycle, that together produced an outcome none of them could produce alone. The market did not collapse to a single winner. It expanded into a durable, multi-drug ecosystem where each component addressed something the others could not. I think there is a genuine case that Huntington’s disease, if the science continues to develop as it appears to be developing, may look similar over time. A patient in the early stages of HD, properly treated in a world where AMT-130 is approved and accessible, might be taking AMT-130 as the foundational intervention (going directly to the striatum, addressing the exon1 fragment, providing the dual suppression mechanism that continuously works against mutant HTT at the source) while also taking a daily oral agent from a program like INVEST-HD that addresses the disease at a systemic level, while also managing residual chorea symptoms with Austedo XR or a successor, while also potentially benefiting from whatever Wave Life Sciences’ allele-selective program produces as it matures. These are not redundant interventions. They are addressing different dimensions of a disease that operates across multiple biological registers simultaneously.
The analogy holds not just scientifically but commercially: the HIV market did not produce one winner and a graveyard of also-rans. It produced a durable, high-value ecosystem of complementary agents that collectively transformed what had been a death sentence into a manageable chronic condition. If that is the trajectory for HD (and I am not asserting it as a certainty, but I think it is a reasonable framework given what the science is showing) then AMT-130 is not one option among several. It is the anchor of the entire regimen. It is the intervention that goes to the root of the problem, around which everything else is built. Which makes what the FDA has done to it not merely an injustice to the people in that conference room, but an obstruction of the foundational piece of what could become a genuinely transformative treatment paradigm for a disease that currently has nothing remotely adequate on offer. For investors willing to think about what that means over a long time horizon: what Gilead did in HIV — identifying the intervention that went to the root of the problem, owning it, and compounding that position into one of the most durable franchises in the history of the biopharmaceutical industry — is the template. The patient populations are not comparable in size, but the structural logic is. The company that owns the anchor therapy in a multi-drug treatment paradigm for a serious, chronic, genetically defined disease does not stay small. Gilead’s HIV franchise is not a story about one drug. It is a story about what happens when you get the foundational science right and then have the patience and discipline to build around it. uniQure, if AMT-130 is approved and the treatment paradigm develops as the science suggests it might, is sitting at an equivalent inflection point. The current market cap reflects none of that.
With that established: I had the opportunity to speak with several people from Novartis during the conference, and what I took away from those conversations was something I want to report carefully because I think it is genuinely important. Their reaction to what the FDA did to uniQure at the Type A meeting was not — as a cynical reading of competitive dynamics might predict — a kind of quiet, neutral satisfaction at seeing a rival program encounter regulatory difficulty. What I observed was something closer to alarm. The word I would reach for is scared, and I use it deliberately. These are people who understand the regulatory pathway for CNS disease-modification programs better than almost anyone outside of the FDA itself, and what they are afraid of is the precedent. If AMT-130 — a program with the biological signal it has, the clinical data it has, and the degree of patient and physician support it has — can be blocked on the grounds that were advanced at the Type A meeting, then no program is insulated from the same treatment. The regulatory risk premium on the entire category of disease-modifying HD therapies just expanded dramatically, and everyone in the room who is running one of those programs felt it.
Wave Life Sciences, Genentech, and the other sponsors round out a picture of a field that is genuinely active, genuinely invested, and genuinely alarmed at what the current regulatory environment means for programs that are trying to do what AMT-130 is trying to do. The collective anxiety I heard from multiple people representing multiple organizations across the day is itself a form of evidence that deserves weight in how you think about this situation.
The Mood of the Advocates
The patient advocates and community members at this conference were not people I would describe as broken or defeated, though they have had more than enough reason to be. They were tired in the way that people who have been fighting hard for a long time get tired, not the tiredness of giving up, but the tiredness of sustained, high-stakes effort over years with far too little to show for it. They were hurt in a way that is specific and personal, because the FDA’s treatment of AMT-130 was not experienced by them as an abstract institutional decision but as something that was done to them, to their families, to people they love. They were angry — genuinely, articulately, righteously angry — in a way that I found both completely understandable and, in a strange way, encouraging, because anger of that quality tends to be productive in ways that resignation is not.
What makes the anger of the HD advocacy community qualitatively different from ordinary patient advocacy frustration is the depth of their knowledge. These are not people who are reacting emotionally to a headline or a press release. They have educated themselves, over years, about the biology of a disease that most people have never heard of. They understand the difference between HTT lowering and HTT silencing. They understand what NfL is and why the biomarker data matters. They have read the clinical trial reports. They attended webinars on the Jeff Carroll data showing that mutant-selective HTT lowering rescues consensus HD genes in ways that pan-lowering does not. They engaged with the Type A meeting process in good faith, submitted comments, organized, made themselves available, and participated in every mechanism that the regulatory system offers patients as a channel for their voices.
They did all of this because they believed that the system, whatever its imperfections, was ultimately operating in a rational relationship to the evidence. The Type A meeting outcome, and the pattern of events surrounding it, including the Bloomberg “failed product” story, the Prasad trajectory through CBER, the contrast with the UK Government Office for Science endorsement, read to them as a demonstration that this belief was misplaced. What they experienced was not a close scientific call that went the wrong way. What they experienced was a betrayal of the premise on which they had been operating. The anger in that room was the anger of people who played by the rules and watched the rules get changed on them.
I met Katie Jackson, who was physically present at the Type A meeting with uniQure. She had been in the room. I am not going to put specific words in her mouth about what she witnessed or how she experienced it, because that is her account to give in her own way and in her own voice. What I can say is that speaking with her left me with no ambiguity about whether the outcome of that meeting was experienced by the people closest to this disease as a legitimate regulatory disagreement. It was not. Her anger was not the diffuse frustration of someone who expected a different outcome and didn’t get it. It was something considerably more specific, and I am going to leave it at that.
The Question
At various points throughout the day, I asked a question of several people — Katie among them, and also a medical professional who was present at the conference, as well as other advocates and community members who have been deeply engaged with the AMT-130 program. The question was simple and deliberately direct:
if your child had symptoms of Huntington’s disease and qualified for AMT-130 under the current eligibility criteria, would you give your child the drug?
I want to explain why I asked it in those terms, because the framing is deliberate and I think it is the right framing. The question is designed to cut through every layer of regulatory procedure, institutional posturing, political maneuvering, and speculative uncertainty and ask the people with the most relevant knowledge and the most direct stake in the outcome what they actually believe about the risk-benefit calculus of this drug. A regulator can invoke a sham surgery requirement. A bureaucrat can hide behind procedural objections. A motivated critic can construct theoretical concerns about long-term safety in a novel modality. When you ask someone who understands the disease, understands the data, and would bear the consequences of the answer — when you ask them what they would do for their own child — the answer is the cleanest possible read of where the biology actually stands.
The answer, from every person I asked, was immediate, unanimous, and unambiguous. There was no deliberation. There was no pause to weigh competing considerations. There was no hedging or qualification. Every single person said yes, without hesitation, and several of them answered before I had finished asking the question.
That answer is the most important thing I can report from the conference. Not the sponsor list. Not the political organizing. Not the film crew or the advocacy strategy or the Congressional outreach plan. The fact that the people who live inside this disease — the people who understand its stakes, who understand what AMT-130’s data actually shows, who would have to live with the consequences of that decision — that those people would give this drug to their own children without a moment’s hesitation is the clearest possible statement about where the biological question stands. The biological question, in other words, has been answered. What remains is everything else.
uniQure
I spent meaningful time with the uniQure team during the conference, and I want to be precise about what I observed because I think it matters both for how you understand the company and for how you understand the state of play in this regulatory fight.
The most striking thing that happened at their booth was not anything uniQure’s people said or did. It was what patients did. Throughout the day, patients came to the uniQure booth (not primarily to ask questions or gather information, though some of that happened) but to offer support. To tell the team that they believed in the work. To let them know that the community understands what the company has been doing and is still behind them. This dynamic is unusual in any professional or commercial context, and it is essentially unheard of at pharma conference booths in the normal course of things. The relationship that has developed between uniQure’s AMT-130 program and the Huntington’s disease patient community is not the normal relationship between a drug company and the people who might one day use its products. It is something more like solidarity, forged over years of shared investment in a scientific program that both parties believe has the potential to genuinely change the disease.
The people I spoke with at uniQure carry a genuine belief in the biology. I want to be careful about how I say this, because investors can sometimes mistake enthusiasm for conviction, and there is a version of biopharma corporate culture where people are trained to perform belief in whatever program they are working on. That is not what I am describing. The belief I observed in the uniQure people I spoke with at this conference was the kind that is grounded in evidence, that has survived disappointment and setback and protracted regulatory difficulty, and that is stronger for having been tested. They are not unaware of the challenges. They are not pretending the path has been smooth but they believe in what AMT-130 is showing in the data, and they are not going to stop believing it because a regulatory process that appears to have been operating in bad faith produced an adverse outcome.
Seeing that belief in the same physical space as the patients whose lives this program is designed to help, watching the interaction between the two, the warmth and the mutual investment in a shared outcome, was genuinely moving in a way I did not entirely anticipate, and I say that as someone who is not generally given to sentimentality about pharma companies or their commercial programs.
The Political Fight
The most significant strategic development I observed at this conference is one that I think investors following QURE need to understand clearly: the HD advocacy community has correctly diagnosed the nature of the problem they are facing, and they are organizing accordingly.
For a long time, and this is a natural and reasonable initial response, the community operated primarily in the scientific and regulatory register. They engaged with the FDA’s processes and they submitted data and comments. They organized around the clinical and biological arguments for AMT-130. They worked within the system because they believed the system was responsive to evidence and to the genuine advocacy of patient communities. That approach was not wrong, and the work it produced (the submissions, the organized advocacy around the Type A meeting, the formal statements to Congressional committees) was substantive and important. However, the Type A meeting outcome clarified something that a growing number of people in the community had been suspecting for some time: the obstruction they are facing is not primarily a scientific or regulatory problem. It is a political one, and it requires a political response.
Jeremy Renz, who was at the conference, has been a central figure in the pivot toward Congressional engagement. The letter from Congressman Rutherford that emerged from that effort was a direct product of the kind of patient-to-representative contact that is now being systematically organized. Advocates at the conference are scheduling meetings with Senator Johnson’s medical liaison as part of an investigation into the FDA’s handling of AMT-130. Active outreach is being coordinated toward other members of Congress, including Representative Auchincloss, who has shown interest in the intersection of rare disease drug development and regulatory reform. The strategy is explicit and deliberate: build enough political accountability around what happened that the obstruction becomes untenable to sustain.
I want to also note something I got wind of at the conference that I cannot independently verify but that I think is worth flagging, with appropriate epistemic caution. Vinay Prasad, during his tenure as CBER director, was apparently in San Francisco throughout the period in question — not in Washington. I am reporting this as something I heard, not as something I can confirm from primary sources, and I am genuinely uncertain what the full explanation is. However, the optics of a CBER director remaining in San Francisco while a major patient community is mobilizing on Capitol Hill over a decision made under his authority are, at minimum, worth noting. A director who was confident in the defensibility of his agency’s decision-making and who wanted to engage with the political accountability that decision was generating would, presumably, be in Washington. Whether Makary was shielding him from that accountability, whether there was some other operational or personal reason for his absence from the capital, or whether there is a connection to the Arnold Ventures funding questions that have been raised in other contexts — I genuinely do not know. I am flagging it as an unexplained data point, not drawing conclusions from it.
What I Came Back With
I want to try to synthesize what the experience of yesterday actually changes or confirms in how I am thinking about the investment thesis and about the trajectory of this regulatory fight, because I think that synthesis is more useful than simply cataloguing what I observed.
The first and most important thing it confirms is that this is no longer, at its core, a biological dispute. The companies that were in that room — Novartis, Genentech, Wave — know that AMT-130 works. The advocates know the biology, because they have educated themselves rigorously over years. The medical professional I spoke with who was asked whether they would give this drug to their own child answered without hesitation. The biological question — does this drug do what it is claimed to do, and does the benefit justify the risk in the population it is designed to serve — has been answered to the satisfaction of every party in that room who has the knowledge to answer it. The ongoing obstruction is not grounded in genuine scientific uncertainty about those questions.
When you layer in what I discussed earlier about mechanism and anatomy, the obstruction becomes even harder to defend on any rational basis. AMT-130 is not one of several interchangeable options in a field with adequate alternatives. It is the only program that goes directly to where Huntington’s disease actually lives — delivered intracranially, acting at the striatum, targeting the exon1 fragment that sits at the core of the pathological process. The oral programs being developed in parallel, however promising they may prove to be, are operating through fundamentally different mechanisms at different anatomical targets. They may turn out to be genuinely valuable complements over time. They will not be substitutes. A disease rooted in what is happening at a specific region of the brain is not going to be fully addressed by anything that does not go directly there, and the people in that room who understand the science know this. The obstruction of the only program that does go directly there — in a uniformly fatal disease with nothing adequate on offer at this level of biological ambition — is not a close call dressed up in procedural language. It is indefensible, and the fact that the broader industry can see that clearly enough to be genuinely frightened by it tells you everything you need to know about where this actually stands.
What remains is a political fight, and the state of play in that fight is more favorable than the current stock price would suggest. The advocacy community is organized in a way it was not six months ago. Congressional interest is not superficial, it involves active engagement with Senate and House offices that are beginning to understand the mechanics of what happened and why it matters. The precedent anxiety that I observed in the Novartis and other industry representatives at the conference creates a broader set of actors with an interest in seeing the situation resolved in a way that restores some degree of regulatory rationality to the space. In addition, the documentary being produced, whenever it is released, will bring the human reality of what I witnessed in that ballroom to an audience that currently has no frame of reference for it.
I have thought seriously about whether I can construct a coherent political rationale for blocking AMT-130 — whether there is a calculation that makes sense from the perspective of whoever has been driving the obstruction — and I cannot. The disease is uniformly fatal. The patient community has no adequate alternatives. The drug has biological signal and clinical data that the people closest to it find compelling enough to answer the hypothetical about their own children the way they answered it. The political downside of approving a drug that helps a desperate patient population with nothing else is essentially nil. The upside of continued obstruction, as best as I can see, is equally nil — unless it is the product of motivations that are not about science or even about conventional regulatory caution, in which case it is presumably fragile in the face of sustained political pressure.
Houman Hemmati is increasingly being discussed as the next CBER director, a development I have noted elsewhere and that is directly relevant to how this situation resolves. If/when he is appointed, he inherits a decision that is already made in the sense that the evidence is in place and the community that will feel the consequences of the decision is mobilized and visible and demanding accountability. The legacy-building opportunity in front of him is, in one direction, genuinely extraordinary: a rare disease with a desperate patient community, a drug with compelling biological support, a regulatory history that is increasingly understood to have been compromised by considerations that have nothing to do with science or patient welfare, and the power to simply correct the record.
The patients I met yesterday in Baltimore deserve that correction. They have waited long enough, they have been patient and organized and engaged and strategically sophisticated in ways that most patient communities never achieve, and they have been met with an obstruction that is increasingly difficult for anyone paying attention to explain in terms that give it any scientific or ethical legitimacy. What happened to them is not a close call that reasonable people can view differently. It is something that the people who were in that room — across backgrounds, across levels of scientific sophistication, across personal relationships to the disease — have reached the same conclusion about.
Give them their drug.
I am long QURE. I attended this conference as an investor and as someone who has been publicly tracking and writing about AMT-130 for an extended period. This is not investment advice. My position history and track record are publicly timestamped and auditable on X.