Why, haven’t you heard? Biotech has been getting the tar kicked out of it the last several weeks. The jury awarded Nektar only $90 million, uniQure’s long-term data eroded more than expected, Liquidia lost a patent battle with United Therapeutics, and Xenon had a safety issue… should we go on? Yields, rates, diesel, de-grossing- it is all so darn complicated. You know what biotech investors need right now? A big win. Better yet, a micro- or small-cap big win, something that comes out of nowhere and surprises to the upside. Conveniently, that’s our passion.
Back in July, we grouped a handful of these into what we called a 2H2026 catalyst cluster, names all converging on an important clinical readout in the back half of the year. What drew us to the group was not just the timing but the range. These names sit all along the risk spectrum: proven biology and novel biology, low-risk registrational bets and high-risk first-of-their-kind readouts, mechanisms validated by approved drugs and mechanisms no one has ever shown work in humans. Some are close to de-risked; others are purely binary.
A quarter later, the slate looks different than it did in July. The window got off to a strong start with ProMIS’s clean safety interim, but there has also been some slippage, and more of the data than we expected now lands in 2027 rather than before year-end. What we first described as a year-end cluster has evolved into a slate running from December into the first half of next year. Below is where each name stands, along with the three we have added since.
Still Live For Year-End
The Trend Is Your Friend
Eupraxia (Nasdaq: EPRX) is expected to report interim data from the placebo-controlled Phase 2b portion of its RESOLVE study of EP-104GI in eosinophilic esophagitis (EoE) in December. We have written about Eupraxia and EP-104GI several times, and our view hasn’t changed: of all the names on this list, this is the one we have the least concern about the underlying biology. We already know fluticasone works in atopic disease, swallowed topical steroids are already used in EoE, and the open-label data from RESOLVE has been consistently strong. Last week, the company provided another update from the open-label portion of the study: roughly two-thirds of the higher-dose patients remained in clinical remission at 52 weeks after a single administration, with no oral candidiasis and no cortisol or glucose issues. The catch is the one we always come back to: open-label, not controlled.
That brings us to a point we think investors need to consider heading into December’s readout. This is an interim analysis, not the final one. The company expects to report roughly 90 patients at three months and 60 to 70 at the six-month timepoint, which is the primary endpoint and the end of the placebo-controlled window before patients cross over. Only about 60% of the study’s patients will be evaluable at six months at the interim, and investors should set expectations accordingly. For patient-reported outcome (PRO) endpoints, SDI and DSQ, where we think the clinical intrigue lies, our understanding is that the interim is powered somewhere in the 70-80% range to detect a placebo-adjusted difference, rising toward 95% once all 120 patients are counted. On DSQ specifically, the magnitude the study is powered to detect at the interim is roughly in line with what Dupixent produced in its registrational program, so if EP-104GI delivers Dupixent-like symptom data, the interim has a real chance of hitting, while a more modest, budesonide-like (Eohilia) effect would more likely show up as a trend than a clean statistical win at this sample size. But, to be clear, on the symptom measures, the trend is your friend. A numerical separation favoring EP-104GI that is approaching significance, with only 60% of the sample size, should be viewed positively, as it would imply EP-104GI reaches significance in the final analysis once all 120 patients are counted. The histology is the safer readout, since biopsy-based endpoints don’t respond to placebo.
The interim readout will also give us an early look at durability, with roughly 45 patients at nine months and 20 to 25 out to a year. This is more of a commercial read-through than a regulatory one. The duration of symptom relief from a single administration of EP-104GI, especially if it reaches 12 months, could be a huge source of commercial differentiation.
December is about whether the controlled data confirms what the open-label data has been telling us for two years. We think the odds are good that it does.
A Good Drug Or A Great One?
Ovid Therapeutics (Nasdaq: OVID) was a name where, in our July note, we highlighted two signal-finding readouts to watch and speculated both might land before year-end, while acknowledging the KCC2 ketamine challenge could slip into early 2027. That is how it has played out. The OV329 photoparoxysmal response (PPR) study remains a year-end event, while the ketamine challenge, along with the OV4071 Phase 1, now reads out in early 2027.
The open-label PPR study of OV329, Ovid’s next-generation GABA-AT inhibitor, is underway in photosensitive epilepsy, testing 5, 7, and 9 mg doses, with data expected around year-end. The PPR study is intended to add another layer of proof-of-mechanism to the company’s earlier TMS work, and the read-through to focal onset seizures is well supported. The photosensitivity model has been used for roughly fifty years, and across the dozens of drugs tested in it, a positive PPR result has correctly predicted clinical antiseizure efficacy for the vast majority, including FOS. Vigabatrin itself is on that list: its PPR-suppressing effect was demonstrated before approval and translated into real-world efficacy. So a clean PPR read for OV329 would put it in good historical company. The PPR model can’t tell us how OV329’s efficacy stacks up against other ASMs, which is the job of the randomized Phase 2 in FOS patients. But as we have highlighted before, even if OV329 only replicates vigabatrin’s efficacy while avoiding ocular toxicity — falling short of the efficacy bar Xenon Pharmaceuticals’ (Nasdaq: XENE) azetukalner has set — it will still become the go-to GABA-AT inhibitor and play a meaningful role in managing FOS. And that is before accounting for its potential in rare pediatric epilepsies like infantile spasms and tuberous sclerosis, where it has first-line potential. As CEO Meg Alexander stated in her presentation at last month’s HC Wainwright conference: “We believe OV329 is going to be a drug. The question is: is it a good drug, or is it a great drug? We are asking and answering that in a phase II study and also a photosensitivity study right now.”
The ketamine challenge study is now earmarked for early 2027, and as we stated in previous notes, this is the study that intrigues us most. Ketamine temporarily makes KCC2 dysfunctional and pushes a healthy brain toward a psychosis-like state, and the study tests whether OV4071, the first oral KCC2 activator to reach humans, can counter it, measured on electrophysiology and biomarkers. It matters because KCC2, if it works, is a very big idea. The eminently quotable Alexander said at a Cantor fireside in September that KCC2 could be “a Karuna or a Cobenfy times five,” a reference to Karuna Therapeutics, the maker of the schizophrenia drug Cobenfy, which Bristol Myers Squibb bought for roughly $14 billion in 2024. She was careful to call the study exploratory, noting that a positive read would be welcome but is not necessary, with the planned Phase 2 schizophrenia study going ahead either way. Nevertheless, we think a positive signal could drive substantial upside, since it would be the first human evidence that a KCC2 activator does what the mechanism promises, and the market currently assigns the platform almost no value.
The Oligomer Referendum
Acumen Pharmaceuticals (Nasdaq: ABOS) is one of the highest-stakes readouts in the cluster, both for Acumen and for the amyloid-beta oligomer (AβO) thesis as a whole. ALTITUDE-AD is a 542-patient Phase 2 testing two doses of sabirnetug against placebo, with the iADRS cognitive and functional scale as the primary endpoint at 18 months and CDR-SB as a key secondary. Topline is still guided to late 2026, which the company reaffirmed at its September investor day. Sabirnetug’s pitch is selectivity: unlike the approved antibodies, which clear plaque (donanemab, lecanemab), it is designed to bind soluble oligomers specifically while largely sparing monomer and plaque, the goal being efficacy with less ARIA. We have laid out our full view in From Aduhelm’s Ashes: Two Affordable Alzheimer Names Targeting Toxic Oligomers, so we will keep it brief here, but this readout sets the tone for the whole oligomer group, ProMIS included.
The bull case is that sabirnetug hits its primary (ideally CDR-SB secondary as well, or at least trending favorably) and with less ARIA than its plaque-targeting antibody cousins. Given the size of the Alzheimer’s prize, the equity re-rates multiples from where it is today, and RA Capital, which owns approximately 30% of Acumen, looks smart for its patience. The bear case is that sabirnetug misses its primary, following in the path of the prior oligomer-engaging antibody to be tested, Genentech/Roche’s crenezumab, which failed in Phase 3. Acumen’s stock gets crushed, and with a cash runway only through early 2027, Acumen winds down clinical operations, and RA Capital uses it as a shell to take one of its incubated companies public later next year. This is about as high-stakes as you get.
Singles And Doubles
Also expecting data before year-end, but on the other end of the risk spectrum, is Talphera (Nasdaq: TLPH), whose Chief Medical Officer said at the HC Wainwright conference in September that “there is essentially no risk to the study.” That is a bold claim for any pivotal trial, but the design backs it up, which is why we flagged Talphera as a lower-risk setup when we introduced it in Approaching The Pivotal Readout With CorMedix At The Table. The NEPHRO-CRRT study’s primary endpoint is activated clotting time (ACT), an objective measure of how long blood takes to clot rather than a clinical outcome, and nafamostat (Niyad) is a serine protease inhibitor that has been standard of care for this use in Japan and South Korea for years. The trial adjusts each patient’s dose until their clotting time reaches the target range, then measures against a placebo that cannot move the endpoint, which is why management can be so confident.
That said, clearing ACT is FDA’s registrational hurdle, not the commercial one. As we highlighted in our earlier note, the two secondary endpoints that matter most to nephrologists and ICU nurses (and payers) are filter lifespan and the number of filter changes over 72 hours. Those will drive adoption if Niyad reaches the market, and they are worth watching in the readout alongside the primary.
What makes the name interesting is the cadence of events that follow a positive readout. Management’s goal is pivotal data around year-end, a PMA filing within roughly three months, and, because Niyad carries Breakthrough Device designation and a six-month review clock, a potential approval and launch in the second half of 2027. And then there’s CorMedix (Nasdaq: CRMD), which holds an equity stake, a board seat, and a 60-day right of first negotiation triggered by the data. If the study reads out as management expects, the most interesting question is what CorMedix does with it.
As we said when we introduced the name, Talphera is a singles-and-doubles investment, not a home run. But given how de-risked the clinical profile looks and the M&A optionality sitting on top, we think the risk-reward is appealing.
Now Early-2027 Stories
Dream In Technicolor
Satellos Biosciences (Nasdaq: MSLE) completed BASECAMP enrollment last week, exceeding its 51-patient target in under nine months, and updated its topline guidance to Q1 2027.
It is worth appreciating the bet Satellos is making with this trial, something we have referred to as ambitious in earlier notes. BASECAMP is a randomized, placebo-controlled Phase 2 study of SAT-3247 (now referred to as forazapadin) in ambulatory boys with Duchenne muscular dystrophy (DMD), and the company chose its primary endpoint, grip strength by dynamometry, and its 12-week placebo-controlled window because it believed that combination gave forazapadin the best chance to show a clean, early functional signal. That is a high-stakes gamble. Twelve weeks is a short runway to ask a regenerative drug to move a functional measure in children, and the company is betting it can. If the bet pays off and forazapadin shows a statistically significant difference against placebo in grip strength, or another functional endpoint, backed by supportive biomarker and regeneration data (likely fat fraction), the equity is going for a ride.
We would, however, prepare investors for a middle-ground outcome. BASECAMP does not end at twelve weeks. After the 12-week placebo-controlled Part 1, every patient, including placebo, continues on forazapadin for a further nine months in Part 2, roughly a year on drug in total. So the Q1 readout is a first look, not the verdict. The middle-ground outcome, and perhaps the likeliest one, is twelve-week data that is encouraging but incomplete, with trends that firm up over the back half of the trial as slower-moving functional endpoints, such as the North Star Ambulatory Assessment (NSAA), come into focus. In that scenario, the right move is patience rather than a snap judgment in either direction.
The range of outcomes here could be gut-wrenching. Ideally, investors get a clean hit at twelve weeks, grip strength separating from placebo with the biomarker and regeneration reads pointing the same way, the outcome that re-rates the stock and puts Satellos in a conversation with FDA about accelerated approval. The middle ground is the immature-but-encouraging read we just described. Then there is the swing-and-miss, where there’s no functional signal, and nothing in the biomarkers holds together. A gut-wrenching range of outcomes, as we said.
What makes Satellos so intriguing is that, unlike its DMD peers, it is doing the hard study first. Satellos, by choice or not, went straight to a randomized controlled trial (RCT), where its peers all took the open-label route and dragged their feet on the RCT. That amplifies the risk, and a clean miss would be unforgiving. But it is also why, if it hits, the upside is the kind investors dream about in technicolor.
Safety First
ProMIS Neurosciences (Nasdaq: PMN) is the one name here that has already reported, and it met or exceeded expectations. The blinded six-month PRECISE-AD interim came back with zero ARIA-E, and not just in the easy patients, but across every genotype, including the APOE4 homozygotes that are problematic for the approved plaque-targeting antibodies. The whole ProMIS thesis rests on the idea that selectively hitting oligomers lets you avoid the ARIA that plagues the plaque-busters, and now we have early evidence of that. The biomarker trends, still blinded, point the right way too.
We would temper the enthusiasm on timing, though. As we laid out in ProMIS Delivered…Now Comes The Harder Part, the real verdict, the unblinded 12-month data with actual efficacy, does not land until Q1 2027. Until then, the stock’s biggest swing factor is not even its own data. It is Acumen’s. A clean sabirnetug readout in December would lift the entire oligomer group and ProMIS with it; a miss would do the opposite, rightly or wrongly. ProMIS has cleared the bar it needed to clear this year. Now it waits for someone else’s trial to set the tone heading into its 12-month data early next year.
Reddy Or Not
Coya Therapeutics (Nasdaq: COYA) is the newest name in our universe, and we recently laid out the full thesis in The ALS Study Nobody Is Watching – Except Dr. Reddy’s, so we will keep it short here. COYA 302, a dual-immunomodulatory biologic for ALS, has Dr. Reddy’s behind it in nearly every way that matters: it holds commercialization rights across major markets, supplies the drug’s abatacept component, and owns a 10% stake in the company. This week the company announced that its pivotal Phase 2/3 ALSTARS study has completed enrollment and reaffirmed guidance for topline data in early Q2 2027. The market isn’t paying much attention. We think it should be.
Catching A Cold
Equillium (Nasdaq: EQ) is a name we have been quiet on since our initial note in April, waiting for the company to solidify the timing of its Phase 1 study. Originally earmarked for mid-year, it slipped into the fourth quarter, with regulatory clearance coming this week and the first patient planned for next month. We laid out the full thesis in Equillium’s Turnaround: AHR, Abivax, and ADAR1, but the short version is this: when your valuation is tied to a much larger peer working the same mechanism, you live by that peer’s equity performance, and you die by it. For Equillium, that peer is Abivax (Nasdaq: ABVX), whose obefazimod is the most advanced drug tied to the AHR thesis, and when Abivax sneezes, Equillium catches a cold. It has caught a bad one, as Abivax has fallen precipitously since the summer and Equillium has been dragged along with it. To be fair, not all of the weakness is peer-related. The Phase 1 slipping from mid-year to the fourth quarter is a self-inflicted execution delay, and that has weighed on the equity in its own right.
The good news is that Equillium now controls its own clock. With Phase 1 cleared, proof-of-mechanism data should be in reach around the second quarter of 2027, and the company can afford the wait. R&D spend is modest, and management has guided that its roughly $57 million in cash as of June should last into 2029. So while the Abivax comp has cut the other way, with the stock sliding and the takeout speculation that once swirled around it quieting down, the balance sheet gives Equillium room to let its own story play out. We still like the mechanism, but the story lacks urgency. With its own catalyst not due until 2027, this is a name to keep on the radar rather than chase today.
It Only Takes One
So there it is: eight names, one slate, spanning the full risk spectrum from Talphera’s near-sure thing to the binary swings at Acumen and Coya. We opened by saying biotech needs a win right now, and the beauty of a group like this is that it probably only takes one. Not all of them will work; that is the nature of the game, but across a cluster this diverse, converging over the next two quarters, the odds that at least one surprises to the upside are better than the market seems to appreciate. We will watch all of them closely and report back as the data lands. In the meantime, we can go back to trying to figure out what de-grossing means…