*TEM price target at the end of the article.*

I’ve written two pieces on Personalis. The first argued the coverage ladder was the thesis and put a $15 target on it. The second, after the immunotherapy MolDX decision landed early, upgraded that to a probability-weighted $24 and leaned into the unit economics. Today the question is moot, because this morning Tempus AI agreed to acquire Personalis for $16.25 per share, roughly a $1.5 billion enterprise value net of the stake Tempus already owned.

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Read together with a wave of new mechanistic biology published this same month, the coincidence is more informative than Roche’s careful corporate language lets on. It isn’t really news that two more Huntington’s drugs failed, this field has buried more candidates than it has advanced. What’s underappreciated is why they failed, and what that specifically implies about the one program still standing.

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I previously wrote about Ionis Pharmaceuticals on June 12, 2025 and the original note went out with the stock around $35 and a $79 target, on the argument that the market had no idea how to price a pipeline this broad and would be forced to learn when the launches landed. Over the following twelve months the stock more than doubled, blew through the target, and topped out at $86.74 in June. Tryngolza’s launch, the HAE approval, the commercial build — the catalysts I said would drive it landed roughly on schedule and mostly better than I modelled.

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I’ve written on both CMPS and GHRS in the past and the connective tissue in both notes was the same claim: the regulatory environment around psychedelic therapy was formalizing in practice even while it stayed restrictive on paper. This month the paper caught up as the FDA has converted its June 2023 draft guidance on psychedelic drug development into a finalized document.

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Cumulative = +1535.41% | YTD = +241.17% | 52-Week = +585.05%

Reminder: Please refer to my original post about this portfolio grouping and background.

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The last piece was about the front end of the industry: who gets approved, and when. This one is about what happens after the approval letter.

Every therapy that clears the new, friendlier CBER has to be manufactured, and every batch has to be released. Before it ships, someone has to prove it isn’t contaminated. That test has, for roughly a hundred and forty years, consisted of a technician smearing a sample on an agar plate, waiting up to fourteen days, and squinting at it under a light. It is the single most antiquated workflow left in modern biomanufacturing, and it sits directly in the critical path of a $2M-a-dose CAR-T.

Rapid Micro Biosystems (RPID) sells the machine that replaces the technician and the squinting.

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When I wrote the RGNX primer last year, the stock was around $9 and the job was to explain why this thing was worth owning: a differentiated Duchenne program, an AbbVie-partnered ocular franchise, and a “golden ticket” Priority Review Voucher waiting on the far side of an MPS II approval. I am now revisiting this name because the single biggest variable working against the entire thesis just flipped.

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This one won’t be a long post but I want to give a glimpse of what might happen if flows finally start hitting the XBI and how that impacts QURE. Most bubble calls start with a stock that’s already expensive but this one isn’t. QURE trades at ~$46 today — below the sell-side’s own base case — while sitting on a near-approved drug and a platform nobody’s paying for. That’s what makes it interesting: there are two separate engines here, and they fire in sequence.

Engine one is the model catching up to a stock that’s already cheap on fundamentals — a re-rate that needs no bubble and no new data. Engine two is what happens when the sector flows arrive and this thin-float, marquee-story name becomes the magnet that catches the most of them. You don’t need to believe in the second to make money on the first but if both fire, you get the move everyone will be talking about after the fact.

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I am writing this from Leesburg, Virginia, where I spent Friday at the Epilepsy Foundation Pipeline Conference — the same room where uniQure presented preliminary data from the first cohort of its GenTLE Phase 1/2a trial of AMT-260 in refractory mesial temporal lobe epilepsy, and where Neurona Therapeutics presented updated data on rezanecel in the same indication. A significant amount of commentary has already gone out framing today’s AMT-260 readout as mixed or disappointing, and I want to offer some nuance, because being in the room produces a materially different picture than reading a press release from the outside.

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There’s a particular kind of company that the market is structurally bad at pricing, and it’s the one whose real asset isn’t the thing in the headline. Everyone who looks at uniQure sees AMT-130 — the Huntington’s gene therapy, the 75% slowing of disease progression at thirty-six months, the FDA drama, the binary that everyone is waiting on. That is fair, and it is genuinely the catalyst, but it is also a profoundly incomplete way to understand what you are actually looking at. If you spend a week reading the company’s patent estate instead of its press releases, a different business comes into focus, and the closest historical rhyme I can find for that business isn’t a Huntington’s story at all.

It’s Alnylam — and specifically, it’s Alnylam as it existed in 2012, when almost nobody was willing to pay for what it would eventually become.

Let me build the case carefully, including the parts that argue against me, because this thesis only holds up if you are willing to carry the bear and the bull in the same hand at the same time.

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There is a version of the Lakefront Biotherapeutics (LKFT) story that sounds like a punchline. A Belgian biotech that spent twenty-seven years failing to get a drug approved, blew its biggest bet on a cell therapy business it then had to quietly shutter after no buyer showed up, cycled through CEOs, and then decided the right move was to rename itself after a geographical feature and start over. That version is not wrong. It is just incomplete, and the part it leaves out is the only part that matters to an investor looking at the stock today.

Lakefront is sitting on approximately €2 billion in cash and financial investments at year-end 2026. The market cap is $1.88 billion. You do not need a spreadsheet to see the problem with that arithmetic, or rather the opportunity in it. The market is currently pricing Lakefront at a meaningful discount to its own treasury, which means you are being handed the pipeline, the Gilead relationship, the new management team, and the buyback authorization for less than nothing. That is the setup in its simplest form, and it is the kind of setup that tends to attract the sort of attention that eventually closes the gap.

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On March 24th, I wrote about a draft FDA guidance that had been sent to the White House for review, with the title “Leveraging Prior Knowledge in the Development of Human Gene Therapy Products Incorporating Genome Editing.”

I told subscribers that this document was different in kind, not just degree — that it wasn’t about manufacturing standards or IND application requirements, but about epistemology itself, about whether prior natural history data, external controls, and cumulative real-world evidence can legitimately serve as the evidentiary backbone of a regulatory submission.

I said the bear case for AMT-130 rested on a single pillar: that the data cannot be evaluated without a randomized controlled trial. And I said that if this guidance were finalized, that pillar collapses — not because the clinical data changed, but because the regulatory standard would explicitly catch up to the scientific reality of rare disease gene therapy development.

This morning, June 2nd, 2026, the guidance published.

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Saloni Dattani’s May biology roundup is mostly devoted to the developments that make this year feel like science fiction, a cure for congenital deafness, recreated snake venom, an emerging generation of antibodies, but tucked near the end is something far less glamorous and, for the purposes of an investor, considerably more interesting: a hair loss pill that actually worked in a registration trial. That pill is VDPHL01, the company behind it is Veradermics, and it trades on the NYSE under the almost too on the nose ticker MANE.

What follows is the case for why this one belongs on your radar, followed by the part of the story that should keep a serious investor honest about what is already priced in.

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This is the final instalment of the Back of the Napkin Bios bubble proxy series. Parts one through four covered AbCellera, Sana Biotechnology, Prime Medicine, and Caribou Biosciences. The thesis running through all of them is the same: after a five-year bear market that punished long-duration biotech assets indiscriminately, a meaningful number of platform companies with genuine science and peak valuations from the 2021 cycle are trading at fractions of what they were worth when capital was free. When the XBI gets bubbly again — and I think it will — these are the names that get re-discovered rather than merely recovered.

I will keep this installment short. These are three names to have on the radar, not three deep theses. The framework is identical to the rest of the series: what does the science do, why is the valuation anomalous, and why does the re-rating work if the macro cooperates.

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Please refer to the 2026 Genomics Stack which covers TXG, TWST, BLLN and others here.

Please refer to my TWST primer and TWST AI-driven thesis.

The spatial biology category has spent most of the last two years being treated as a cautionary tale, a casualty of the broader life science tools drawdown rather than the foundational platform shift it actually represents. With Atera now launched, the patent overhang largely resolved, and the financial profile improving in a way the tape has not yet fully priced, 10x Genomics looks to me like the cleanest picks-and-shovels exposure to a category that is still in its first inning. This primer is intended to lay out the business, the competitive position, and the reasons I am giving this name serious consideration as the life science sector exits the valley of despair.

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Biohaven (BHVN) trades at roughly $9 today, down from $60+ in mid-2024. The 85% drawdown happened in stages through 2025, with each leg of the decline accompanied by a sell-side capitulation that culminated in RBC’s Leonid Timashev cutting his price target from $54 to $21 in May, to $19 in August, and to $9 in November. He has since walked it back to $22, initially in January and again at $23 in early March before trimming a dollar on the most recent quarterly. The stock has barely moved against this re-rating.

That’s the setup that put BHVN on my watchlist. The sell-side whipsaw doesn’t tell me the stock is mispriced in a particular direction but it tells me the name is mispriced somewhere along that path, and the question is which end of the swing was wrong. After working through the most recent RBC notes, I think there is a credible case that the current price is anchored to the November capitulation rather than to anything resembling a forward-looking view of the assets. Whether that gap closes from here, and on what catalyst, is the question I’m trying to answer.

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Two updates worth front-loading before the unit economics work.

First, the immunotherapy coverage decision arrived on May 12, 2026, considerably earlier than BTIG’s mid-2026 window and against a guidance baseline that explicitly excluded it. MolDX expanded coverage of NeXT Personal to include immunotherapy monitoring across late-stage solid tumors, supported by the Vall d’Hebron published evidence. The stock spiked roughly 19% on the news, which both validates the coverage ladder framework and meaningfully de-risks one of the three named catalysts from the original post. Two more (CRC and bladder) remain outstanding, but the most contested one is now live.

Second, the November 2025 MolDX rate update gave us hard numbers to anchor the per-test economics. The initial Dx Breast MRD Recurrence Monitoring Test (the tissue-plus-baseline-plasma test, ordered once per cancer diagnosis) reimburses at $4,266. The Single Plasma Test (the recurring surveillance assay, ordered up to four times a year for up to six years) reimburses at $1,164. Those are the two prices that drive everything that follows.

The original post established why the technology and the coverage ladder matter but what it didn’t do is build a defensible model of what each test earns, how volume scales, where gross margin lands as the mix shifts, and what the resulting valuation range looks like under explicit assumptions. So that’s what this piece does.

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This is Part 4 of an ongoing series on ‘biotech bubble proxies’ — names with the platform architecture, peak valuation history, and clinical de-risking profile to become generational multi-baggers when the next biotech cycle arrives. For Part 1, please refer to my piece on AbCellera. For Part 2, please refer to my piece on Sana Biotechnology. For Part 3, please refer to my piece on Prime Medicine. For the original post on Caribou, please refer here.

The cell therapy industry has produced two of the most significant acquisition premiums in modern biotechnology. Gilead paid $11.9 billion for Kite Pharma in 2017 before a single commercial dose of Yescarta had been administered to a paying patient. Bristol-Myers Squibb paid $11 billion for Juno Therapeutics the following year on essentially the same calculus. The market had looked at CAR-T cell therapy, concluded that the ability to engineer a patient’s own immune cells to destroy cancer represented a generational therapeutic advance, and acted accordingly. Both acquisitions happened before approval. Both were vindicated by the clinical outcomes that followed.

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This is Part 3 of an ongoing series on biotech bubble proxies — names with the platform architecture, peak valuation history, and clinical de-risking profile to become generational multi-baggers when the next biotech cycle arrives. For Part 1, please refer to my piece on AbCellera. For Part 2, please refer to my piece on Sana Biotechnology.

Every few years the gene editing story gets told again, with better tools and higher expectations. The market prices the newest version to infinity, the clinical data arrives on a timeline inconsistent with those expectations, and the correction is brutal and indiscriminate. The companies that survive the correction with their science intact and their mechanisms validated are not the ones that get re-rated, they are the ones that get re-discovered. The distinction matters because discovery feels different from recovery. Recovery is a BIG grind but discovery is a re-rating.

Prime Medicine (NASDAQ: PRME) is not the gene editing story the market told in 2020. It is a more precise version of that story, built on a more sophisticated mechanism, founded by the scientist who understood the limitations of the earlier tools better than anyone else alive and spent years building something that addresses them. I am not buying it today, and I will explain precisely why. However, I am watching it closely enough that it warrants the full treatment, because the setup has a shape I recognize.

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