PoA = probability-of-approval (0–100), banded below.
This issue: A live neurology presentation today, true regulatory binaries into early December, two major events that already hit (ziftomenib and mitapivat), and an updated Retail Lens on how the tape behaved around $AGIO’s drawdown.
Featured Event (Next 7 Days)
GTx-104 — $GRCE ( ▲ 1.27% )
Date: Nov 21 • Event: Phase 3 Data Presentation (STRIVE-ON) • PoA (regulatory, NDA already filed): 80
IV formulation of nimodipine for aneurysmal subarachnoid hemorrhage (aSAH). The pivotal STRIVE-ON Phase 3 safety trial already read out positively in February 2025, meeting its primary endpoint; the full dataset underpins an NDA accepted in August 2025 with an April 23, 2026 PDUFA date.
Why today still matters:
This is not a fresh “data binary” — today’s late-breaking presentation at SVIN is about refining the story (benefit–risk, consistency, ICU workflow fit) in front of specialists and investors. With a first-in-class ICU delivery play and a defined PDUFA date, the incremental risk is about perception and commercial positioning, not whether the trial worked.
On Deck (Nov 22 – Dec 15)
Events prioritized by impact and proximity; ordered by date.
Urcosimod — $OKYO ( ▲ 9.95% )
Nov 22 • Event: Phase 2 NCP Data Presentation / Development Update • PoA (for next major step): 30
Neuropathic Corneal Pain (NCP). A single-center Phase 2 study produced a striking signal: ~75% of per-protocol patients on 0.05% urcosimod achieved >80% pain reduction over 12 weeks.
Why it matters:
The top-line efficacy is already public. The real binary is whether multi-center plans, regulatory feedback, and any expanded safety data sustain that high signal or reveal “single-center magic.” PoA here is for clean reproducibility + credible path to registration, not the already-known headline.
TransCon CNP (navepegritide) — $ASND ( ▼ 1.46% )
Nov 30 • Event: PDUFA (Achondroplasia) • PoA: 80
Once-weekly CNP prodrug for children with achondroplasia. Priority Review is in place, supported by Phase 3 data demonstrating significantly higher annualized growth velocity versus placebo.
Watch the label:
The fight is commercial against Voxzogo and future entrants. Look for:
Label language on proportional growth and safety,
Dosing convenience vs. injections,
Any restrictions that would blunt uptake.
Avance® Nerve Graft — $AXGN ( ▲ 6.04% )
Dec 5 • Event: PDUFA (Biologic BLA) • PoA: 72
Human nerve allograft transitioning from 361 HCT/P to full biologic regulation. FDA extended the goal date to Dec 5, 2025 after a Major Amendment to the BLA, mainly to review additional manufacturing/facility information.
Why it matters:
This is a CMC/quality binary more than a clinical one. Base case: procedural delay and eventual approval. Bear case: lingering concerns on consistency/supply chain that force further delay or restrictions.
ORLADEYO (berotralstat, oral granules) — $BCRX ( ▲ 0.85% )
Dec 12 • Event: PDUFA (Pediatric HAE 2–11 years) • PoA: 86
Oral prophylactic for hereditary angioedema (HAE) in children aged 2–11. The NDA was accepted with an initial Sept 12 PDUFA date and Priority Review; subsequent company and sell-side commentary now anchor expectations around a Dec 12 decision.
Why it matters:
If approved, ORLADEYO becomes the first targeted oral prophylactic for HAE under 12, bolstering a franchise already approved in ≥12-year-olds and competing against injectables and new RNA-based prophylactics.
Resolved This Week
Outcomes tracked against prior framing.
Plozasiran (REDEMPLO) — $ARWR ( ▲ 5.22% )
Event: PDUFA (FCS) • Outcome (Nov 18): Approved
FDA approved plozasiran (brand: REDEMPLO) as an siRNA therapy to reduce triglycerides in adults with familial chylomicronemia syndrome (FCS), supported by robust PALISADE Phase 3 data (median ~80% triglyceride reduction and fewer pancreatitis events).
Context:
First-in-class siRNA for FCS and Arrowhead’s first FDA approval. This was a high-PoA event; the real debate now shifts to pricing, access, and the legal fight with Ionis.
Ziftomenib (KOMZIFTI) — $KURA ( ▲ 2.37% )
Prior Pulse Status: On Deck (Nov 30 PDUFA, PoA 80)
Outcome (Nov 13): Approved Early
FDA approved ziftomenib (KOMZIFTI) for adults with relapsed/refractory AML harboring an NPM1 mutation, ahead of the PDUFA date. The label includes a Boxed Warning for differentiation syndrome, exactly where the safety debate was centered.
Takeaway:
Regulators validated the efficacy signal in the NPM1-mutant population but locked in DS as the key management issue. From here, the binary is commercial: can KOMZIFTI expand use without DS fears capping real-world adoption?
Mitapivat (PYRUKYND) — $AGIO ( ▲ 0.49% )
Prior Pulse Status: On Deck (Dec 6 Phase 3 Topline, PoA 98; stock had already halved)
Outcome (Nov 19): Mixed Phase 3 RISE UP Data
The RISE UP trial in sickle cell disease met one primary endpoint (hemoglobin response) and key hemolysis-related secondaries, but failed the co-primary of annual sickle cell pain crises and a key fatigue endpoint.
Takeaway:
Biology was largely confirmed; the commercial thesis was damaged. The pre-data 50% drawdown now looks less like “random panic” and more like informed selling around trial quality and the bar for crisis reduction.
Phase 1/2a Program — $CMND ( ▼ 5.89% )
Prior Pulse Status: Speculative early-stage data
Outcome (Nov 18–20): Positive Topline
Company reported favorable initial safety/tolerability and a signal consistent with continued development. Market reaction was constructive but measured (early stage, long time-to-value).
Takeaway:
Fits the pattern: good early safety + directional efficacy = financing/speculation optionality, not an immediate derisk of the equity story.
This Week on the Tape — Biotech
Context only; not investment advice.
1. The $AGIO ( ▲ 0.49% ) Breakdown (Post-Data Reality Check)
The puzzle going into this week was simple: why did a “98% PoA” setup see its equity cut in half pre-print? RISE UP answered it. The drug clearly improves hemoglobin and markers of hemolysis, but missing the crises endpoint and fatigue measure means:
Payer leverage goes up,
Peak-sales narratives reset downward,
Competitive positioning in SCD is much less clear.
Net: the tape was (grimly) right. It was discounting a partial win that would not justify the prior valuation.
2. Regulatory Wins vs. Price Action $ARWR ( ▲ 5.22% ) , $KURA ( ▲ 2.37% )
Both plozasiran and ziftomenib secured clean approvals in high-need rare settings. Yet:
The pre-event run-ups and crowded “high-PoA” positioning meant approvals were treated as liquidity events, not upside surprises.
Price action reinforced the current regime: approvals in well-telegraphed programs often mark local tops, not fresh legs higher.
3. Micro-/Mid-Cap Selectivity
Names with clear, near-term binaries and clean balance sheets still attract targeted flows; everything else trades like a funding vehicle. The On Deck list (TransCon CNP, Avance, pediatric ORLADEYO) sits at that intersection of:
Defined dates,
Concrete pathways,
Credible sponsors.
Retail Lens
How to think about the “-50% Pre-Data” pattern after $AGIO ( ▲ 0.49% ) .
When a stock collapses 30–50% in the weeks before a binary, one of two things is usually happening:
Scenario A – Information Leak / Informed Exit
Sophisticated holders gain conviction that the trial will miss the economic endpoint, even if some biomarker looks good.
They exit or de-risk quietly, but in illiquid names the footprint is obvious.
Post-data, you see “partial wins” that don’t justify the old market cap — as with $AGIO ( ▲ 0.49% ) ’s failure on crises and fatigue despite strong hematology.
Scenario B – Forced Seller / Portfolio De-risk
Macro or fund-specific issues cause liquidations unrelated to the asset itself.
If data hit, you get a violent snap-back as fundamentals and positioning realign.
Working Rule of Thumb
A 10–20% drift into data can be noise.
A >30% sustained collapse is a signal: you may not know which scenario you’re in, but the burden of proof flips.
High PoA on biology does not immunize you from a broken commercial endpoint, shifting regulatory goalposts, or trial-design landmines.
PoA Framework (Snapshot)
PoA bands:
High: >70
Moderate: 40–70
Speculative: <40
Construct:
Five-factor model:
Study design & endpoint rigor,
Prior data strength (Ph1/2/3 and class read-through),
Safety / CMC and manufacturing risk,
Regulatory precedent and division quirks,
Sponsor execution and balance-sheet runway,
…then calibrated by division-specific base rates and, where relevant, implied volatility and positioning. Directional only; not a substitute for primary diligence.
Disclaimer
This newsletter is for informational and educational purposes only and does not constitute investment advice, a recommendation to buy or sell any security, or an offer to provide investment advisory services. All views are based solely on publicly available information and historical regulatory behavior. Biotech and pharmaceutical securities involve substantial risk, including the risk of complete loss of capital. Always conduct your own due diligence.