Wave Life Sciences

Phase A — Understand the business

Lens 1 · Company Overview

Wave Life Sciences Ltd. (Nasdaq: WVE) is a clinical-stage biotechnology company developing RNA medicines (oligonucleotides) built on its proprietary discovery platform PRISM. It is incorporated in Singapore (7 Straits View, Marina One East Tower), but operates almost entirely from the US — corporate HQ + R&D in Cambridge, MA (~44,000 sq ft) and an internal cGMP oligonucleotide manufacturing facility in Lexington, MA (~90,000 sq ft), plus lab/office space in Japan. It is a large accelerated filer with 188,254,954 ordinary shares outstanding as of 2026-02-19; the aggregate market value of non-affiliate shares as of 2025-06-30 was $851.0M.

What it actually does — and why it is unusual. Wave is a "chemistry-first" oligonucleotide house. Its differentiator is stereochemistry control — it manufactures stereopure oligonucleotides (atoms purposefully arranged at each backbone linkage) versus the stereorandom mixtures sold/developed by rivals. Its founding example: mipomersen, a 20-mer with 19 phosphorothioate linkages, is a mixture of >500,000 stereoisomers (2¹⁹); Wave builds defined single stereoisomers. The platform spans five modalities — RNAi (silencing, branded "SpiNA"), RNA editing (A-to-I via endogenous ADAR enzymes, branded "AIMers"), splicing, antisense, and bifunctional constructs. The strategic moat-claim: simplified delivery (GalNAc conjugation or free uptake) that avoids lipid nanoparticles (LNP) and AAV viral vectors, sidestepping their toxicity and immunogenicity baggage.

How it makes money today (and tomorrow). Today: only collaboration revenue from GSK (no product sales since inception, none expected for years). Tomorrow (the bet): product sales from a wholly-owned pipeline (obesity, AATD, DMD, HD, PNPLA3) plus milestones + low-teens royalties from GSK-advanced programs.

• Customers / partners: the single named commercial counterparty is GSK (collaboration + license). Companion-diagnostics partner Asuragen (now Bio-Techne) for the HD program's SNP-phasing test. The research-layer customers.csv is empty (no product customers exist yet).
• Suppliers: hybrid manufacturing — internal Lexington cGMP plant + external CMOs for drug substance/product.
• Competitors: the oligonucleotide/RNA-medicines field — Alnylam, Ionis, Arrowhead (platform peers) plus indication-specific rivals (Novo Nordisk / Eli Lilly in obesity; Sarepta in DMD; see Lens 3).
• Contract structure: GSK collaboration is cost-reimbursed for collaboration programs ("all of our costs and expenses are prepaid by GSK" for GSK-partnered target-validation work) plus milestone + royalty economics — see Lens 4 for the deal anatomy.

Commercial-layer note: the genomics KB wiki files (bottlenecks.md, supply-chain.md, positioning.md, market-structure.md, capex.md) referenced by company-context.ts are missing on the shelf — so Lenses 1-4 are grounded in the filings + web rather than a pre-compiled commercial layer.

Lens 2 · Supply Chain

Wave's "supply chain" is a drug-development value chain, not a goods chain. Mapped upstream → company → end customer with named stakeholders:

1. Inputs / chemistry suppliers — phosphoramidite reagents and specialty nucleoside chemistry feed Wave's stereopure synthesis. Two named co-ownership IP partners on synthetic methodology: University of Tokyo (synthesis methods/reagents, patents to 2031) and Shin Nippon Biomedical Laboratories, Ltd. (patent families to 2033-2035). The Japan lab footprint ties to this Japanese chemistry heritage.
2. Manufacturing (the chokepoint Wave chose to own) — internal cGMP plant, Lexington MA (operational since Q4 2017, scales from 1 µmol to "potential commercial scale") + external CMOs for overflow / commercial supply. Owning manufacturing is the deliberate de-risk: oligonucleotide CMO capacity is a known industry bottleneck, and Wave avoids the LNP/AAV viral-vector contract-manufacturing crunch entirely by using GalNAc/free-uptake delivery.
3. CROs — third-party contract research orgs run the preclinical and clinical trials (INLIGHT, RestorAATion, FORWARD-53, SELECT-HD).
4. Companion diagnostics — Asuragen / Bio-Techne supplies the AmplideX PCR-based HTT CAG-repeat + SNP-phasing test that gates HD patient selection for WVE-003.
5. Development/commercial partner — GSK takes GSK-selected programs through IND-enabling → clinical → commercial; Wave keeps its own programs in-house through commercialization (or out-licenses, as it did and then un-did with AATD).
6. End customer — eventual patients/payers across obesity (mass market, ~1B globally / 175M US+EU), AATD (~200k Pi*ZZ US+EU), DMD (~1 in 5,000 boys), HD (~200k US+EU), PNPLA3 liver disease (~9M US+EU homozygous).

Single-source / chokepoint reads: (a) ADAR-editing depends on endogenous enzyme levels — the entire AIMer mechanism rests on the patient's own ADAR being present and active in the target tissue; this is the platform's deepest scientific dependency. (b) Stereopure synthesis know-how is concentrated internally — the moat and the manufacturing chokepoint are the same asset. (c) GalNAc conjugation tropism is liver-centric — extra-hepatic delivery (adipose, muscle, CNS, kidney) is preclinically demonstrated but clinically unproven at scale, so the "broad applicability" claim is partly a promise.

Lens 3 · Competitive Advantages (moats)

The moat thesis (Wave's telling): stereochemistry control + multimodality + LNP/AAV-free delivery = best-in-class, broadly-applicable oligonucleotides protected by a deep IP estate. Assessed adversarially:

• IP / process moat (real, but contestable). Patent families covering (i) synthetic methodologies/reagents (20-yr terms 2029→2045+), (ii) stereopure compositions (2033→2045+), and (iii) product-specific filings. Issued patents in US/EU/Japan. This is a genuine durable asset if stereopurity proves to matter clinically — which is itself the contested scientific claim (rivals sell stereorandom drugs that work; Alnylam/Ionis are commercial without stereopurity).
• First-in-class RNA editing (the crown jewel). WVE-006 (AATD) is "the most advanced program currently in clinical development using an oligonucleotide to harness an endogenous enzyme for RNA editing" — the first to show A-to-I editing in non-human primates with single-stranded GalNAc oligos (foundational Nature Biotechnology 2022 paper). If RNA editing becomes a category, Wave has a credible claim to having opened it. Competing editors include Korro Bio, ProQR, and big-pharma editing efforts — Wave's lead is measured in clinical quarters, not years.
• Delivery moat (differentiated vs. one alternative). Avoiding LNP/AAV removes a real toxicity/immunogenicity class — but the comparison is to some delivery approaches, not all; GalNAc-siRNA is exactly the delivery Alnylam/Arrowhead also use, so Wave is not uniquely advantaged in the liver. The genuine edge is extra-hepatic free-uptake/SpiNA reach (adipose, muscle, CNS), still mostly preclinical.
• Bargaining power: weak today. A pre-revenue, cash-burning company that regained a partnered asset (AATD) it now must fund and partner alone has limited leverage. GSK holds the option-rich end of the collaboration. Wave needs partners more than partners need Wave — the SELECT-HD/WVE-003 registrational study is explicitly gated on finding "a prospective strategic partner".

Verdict on the moat: a real platform/IP/know-how moat whose value is entirely contingent on stereopurity + endogenous-editing producing clinically differentiated drugs. It is a "moat that pays off only if the science is right" — not a moat that protects cash flows (there are none).

Lens 4 · Segments

Wave has no product segments — it is single-platform, pre-revenue. The only revenue line is GSK collaboration revenue, recognized under ASC 606. Revenue by year:

This is the most misread number in the file. Collaboration revenue is not a growing business line — it is the amortization of the $170M GSK upfront + milestones over performance obligations. The FY24→FY25 collapse ($108M→$43M) is upfront-recognition winding down. The Q1 2026 spike to $38.2M is not good news: $35.9M of it was the remaining deferred AATD revenue recognized in a lump because Wave terminated the GSK AATD license and took WVE-006 back. Deferred-revenue balance fell from $44.4M (current) at YE2025 to $9.4M at Q1'26 — the GSK revenue tailwind is largely spent. Going forward, collaboration revenue is small and lumpy until new milestones trigger.

The GSK deal anatomy (the real "segment" of value):

• Effective Jan 2023; $170M upfront = $120M cash + $50M equity (10,683,761 shares at $4.68 — note: roughly today's share price, a brutal anchor).
• Two discovery collaborations: Wave advances up to 3 programs on GSK genetic insights; GSK advances up to 8 programs on PRISM.
• Milestone ceiling: up to $2.8B (≈$1.2B init/dev/launch + ≈$1.6B commercial) + tiered royalties into the low-teens % across the 8 GSK programs.
• GSK prepays all collaboration-program costs — a non-dilutive R&D subsidy. As of Q1 2026, GSK had selected four programs to advance to development candidates.
• Key reversal: WVE-006 (AATD) was originally GSK-licensed; Wave regained full rights in Feb 2026. Double-edged: Wave keeps 100% of AATD upside but now funds and must re-partner it alone.

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Phase B — Measure performance (+clinical overlay: Lens 5 → pipeline-by-phase; Lens 7 → catalyst calendar + mechanism comps)

Lens 5 · Pipeline by phase (swaps "Earnings Result")

The asset table is the company. Programs, modality, indication, stage, next catalyst, and read:

Pleiotropic / dosing axis (the surviving WVE-007 angle): the differentiation is no longer "more weight loss" — it is (1) twice-yearly subcutaneous dosing (vs weekly GLP-1 injections, with up-to-68% GLP-1 discontinuation cited), (2) muscle preservation / lean-mass gain where GLP-1s strip ~11-34% lean mass, and (3) visceral-fat-specific loss. The intended positioning has visibly pivoted toward incretin add-on and post-incretin maintenance — i.e., a complement to GLP-1s, not a replacement.

Lens 6 · Earnings Calls (sentiment trend)

Transcripts are absent from the research layer (transcripts/ empty; ingest-transcript.ts not run per Wave-mode boundaries) — so this lens is ``, dated, and is a sentiment read on management's public framing across the key 2026 events:

• JPM Healthcare Conf (Jan 2026): maximally bullish — "Accelerating Development of WVE-007 (INHBE siRNA) for Obesity and Rapidly Advancing RNA Editing Portfolio"; obesity framed as the value driver.
• FY2025 results + Dec 2025 INLIGHT 3-mo interim (late Feb 2026): "positive interim" — visceral fat / muscle / durable Activin E emphasized; cash runway extended into late 2028 flagged as the headline reassurance.
• 6-month INLIGHT readout (Mar 26, 2026): the tonal break. Management led with visceral fat −14.3% and muscle preservation; the market led with body weight −0.9%. Stock −≈50% same session. Framing shifted decisively from "standalone obesity drug" to "add-on / maintenance + body-composition."
• WVE-006 AATD rights regained (Feb 2026): spun as conviction ("accelerate regulatory engagement with full control").
• Q1 2026 results (Apr 28, 2026): steady-state — runway to Q3 2028, DMD NDA 2026, AATD feedback mid-2026, four GSK programs selected.

Recurring phrases: "first-in-class," "best-in-class chemistry," "muscle preservation," "twice-yearly dosing," "rapidly advancing RNA editing." What they stopped saying: standalone weight-loss superiority vs GLP-1s. The sentiment arc is promotional-confident → defensive-reframing, classic for a clinical-stage name after a headline miss. Treat the optimism with the usual clinical-stage discount.

Lens 7 · Catalyst calendar + mechanism comps (swaps "Comps")

Catalyst calendar (what de-risks or kills each program, and when):

Mechanism / modality comps (NOT P/E — clinical-stage):

The comp read: the RNA-medicines platform category is richly valued (Alnylam/Ionis at ~12x sales as profitable-or-near-it commercial leaders). Wave sits at the bottom of the ladder — ~$1.2B cap, no product, the only clinical-stage name here without an approved drug. The bull case is that one validated asset (DMD approval or AATD accelerated path) re-rates Wave toward Arrowhead's "first-approval" zip code; the bear case is that Wave is a perpetual-platform-promise name that never crosses into the commercial tier. Direct EV/Sales / P/E multiples for WVE are n/a (no revenue base to anchor them); any such figure would be fabricated.

Lens 8 · Stock-Price Catalysts (what the tape reacts to)

The 5-year pattern is unambiguous: WVE trades on single clinical readouts, violently. Recent moves:

• 2026-03-26: −≈50% in one session ($12.30 → $6.20 close) on the INLIGHT 6-month obesity data (body weight −0.9% placebo-adj). BofA cut to $21, Wells Fargo to $13; "two firms chopped targets ~half"; Mizuho raised to $27 — the analyst spread itself signals genuine disagreement.
• A prior session shows a +120% spike on obesity body-composition data ("deep fat reduction, muscle gain"), i.e. the same program whipsawed the stock both directions within the cycle — proof the name is a pure data-event vehicle.
• As of 2026-06-05, ~$5.73; market cap ~$1.19B as of mid-June.
• The $402.5M equity raise in Dec 2025 (which set up the runway-to-2028) priced before the March crash — new holders are now deeply underwater, and the GSK equity at $4.68 (Jan 2023) is roughly back at-the-money.

What the market actually reacts to for WVE: (1) obesity (WVE-007) clinical numbers above all else — it is the swing factor; (2) regulatory pathway signals (AATD accelerated approval, DMD NDA); (3) capital raises (dilution). It does not meaningfully react to GSK collaboration revenue accounting. Macro/sector beta (XBI) matters at the margin but program data dominates.

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Phase C — Judge people & books

Lens 9 · Management

• CEO — Dr. Paul Bolno (President & CEO since 2013; led the 2015 IPO). MD (MCP-Hahnemann), MBA (Drexel); ex-GSK (VP Worldwide BD, Head of Asia BD & Investments, Head of Global Neuroscience BD) and Two River. Track record: built Wave from inception into a multimodal platform with internal manufacturing and a marquee GSK deal — but 13 years in, the company is still pre-revenue, has accumulated a $1.35B deficit, and the stock is near its GSK-investment price. He is the rare CEO who literally negotiated the other side of his company's biggest deal (GSK alum striking the GSK collaboration) — a relationship asset and a related-network flag at once. Also chairs the board of ExpressionEdits and a UK nucleic-acid accelerator (NATA) — outside commitments to note.
• CFO — Kyle Moran (joined 2014, CFO since 2020; built the finance function through IPO). Long tenure, continuity.
• Tenure & skin in the game: founder-era, long-tenured leadership. Institutional ownership ~89.7% — a heavily-institutional float, typical of a story-stock biotech. Insider selling flagged: director Adrian Rawcliffe exercised 42,000 options and sold for ~$630k on 2026-01-08 (i.e., before the March crash). One director's option-exercise sale is not a smoking gun, but the timing — pre-readout, after the JPM ramp — is worth logging. Insider-transactions CSV is absent from the research layer, so quantified insider ownership % is n/a beyond the web institutional figure.
• Capital allocation: the defining trait is serial equity issuance — WASO went 106M (FY23) → 138M (FY24) → 169M (FY25) → ~200M weighted (Q1'26), i.e. ~2x dilution in three years. Funded entirely by equity + GSK; zero debt. The Dec 2025 $402.5M raise was well-timed (pre-crash) and bought runway to Q3 2028 — defensible capital-allocation given the binary catalyst calendar. Regaining AATD from GSK was a de-partnering decision that adds funding burden — a conviction bet on owning the editing upside.
• Founder vs professional manager: professional-manager/physician-scientist archetype running a founder-era platform. Implication: deep scientific credibility and BD pedigree, but the scoreboard (13 years, no product, perpetual dilution) is the bear's exhibit A.

Lens 10 · Forensic Red Flags

Acting as a forensic analyst. The accounting is clean and simple — a pre-revenue biotech with one revenue stream, no debt, and a full valuation allowance. The risks are clinical/structural, not forensic. Income statement / balance sheet / cash-flow scan:

• Revenue recognition (the one real judgment area). All revenue is GSK collaboration revenue under ASC 606 — management flags it as a critical accounting policy requiring "significant judgment" on performance-obligation count, transaction price, and timing. The Q1'26 $35.9M AATD-termination revenue pull-forward is the live example: a contract event, not operating performance. Watch future quarters for similarly lumpy, event-driven revenue — it can flatter optics.
• Cash vs earnings divergence (benign, expected). Net loss Q1'26 $(26.1)M but operating cash burn $(59.6)M — the gap is the $28.2M deferred-revenue runoff + $13.5M accrued-expense decline. Normalized quarterly burn is ~$55-60M. FY2025 net loss was $(204.4)M. No receivables/inventory build to worry about (no products).
• SBC / dilution (the structural drag, not a fraud flag). Additional paid-in capital rose $228.4M→$237.4M in one quarter; non-cash charges ~$11.4M/qtr include share-based comp. The story is dilution-by-design, fully disclosed — WASO ~2x in 3 years. Not flattering non-GAAP because Wave reports straightforward GAAP losses (no adjusted-EPS games here).
• Going concern: not flagged. $544.6M cash funds ops to Q3 2028. No debt, no covenants. A $250M ATM shelf (Jefferies) is open and unused this quarter — optionality, and a future dilution lever.
• Series A preferred: 3,901,348 Series A preferred shares converted to ordinary in Q1 2026 (carrying value $7.9M moved to equity) — cleanup, removes a small overhang.
• Singapore IP-law (Section 34) exposure — the genuine oddity. Wave filed patents outside Singapore without the required prior Registrar authorization. It has submitted ~140 patent applications to IPOS for review; violation of Section 34 is a criminal offense (fine up to S$5,000 and/or up to 2 years imprisonment), though to date the Registrar has only "compounded" offenses for S$50-S$150 per case. Financial exposure is immaterial; the headline risk (criminal-offense language attached to the patent estate) is the real concern, and the Delaware redomiciliation plausibly reduces future exposure.

Regulatory findings (required sub-section):

• SEC Litigation Releases: None. Verified via SEC EDGAR EFTS (LR), period 2021-06-30→2026-06-30.
• SEC AAERs: None.
• Non-SEC enforcement (FTC/DOJ/FDA/CFPB): web search for "Wave Life Sciences" (FTC OR DOJ OR FDA OR consent decree OR settlement OR fine OR penalty) enforcement surfaced no material enforcement actions — only routine FDA interactions (Orphan Drug / Rare Pediatric designations, accelerated-approval discussions), which are favorable regulatory engagement, not enforcement.
• 10-K Item 3 (Legal Proceedings): "We are not currently a party to any material legal proceedings.".
• Conclusion: No material regulatory or legal findings — verified via SEC EDGAR EFTS (LR, AAER), web search, and 10-K Item 3 as of 2026-06-30. The only quasi-regulatory item is the Singapore Section 34 patent-filing matter (immaterial financially; disclosed).

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Phase D — Project & stress-test (+clinical overlay: Lens 11 → rNPV + runway-to-catalyst)

Lens 11 · rNPV + runway-to-catalyst (swaps "Forward Projection / EPS")

No EPS projection — Wave is pre-revenue and will post GAAP losses for years; an EPS line would be fabricated precision. The two questions that matter:

(1) Does cash runway reach the next value-inflection catalysts? — YES, comfortably.

• Cash $544.6M (Q1'26); normalized burn $55-60M/qtr ($220-240M/yr). Management guides runway to Q3 2028. That clears: AATD FDA feedback (mid-2026), DMD NDA (2026) and a potential approval/decision, WVE-007 Ph2a MAD + combo data, and WVE-008 CTA — multiple binary catalysts funded without a forced raise. The $250M Jefferies ATM is dry powder if they choose to opportunistically top up.

(2) Rough rNPV framing (illustrative, every input ``, NOT a model output to trade on):

• WVE-N531 (DMD): nearest to cash. Exon-53 addresses ~8-10% of DMD; competing accelerated-approval dystrophin drugs exist (Sarepta franchise). A successful accelerated approval could support a few-hundred-$M annual franchise; risk-adjusted at a modest PoS given FDA's heightened post-Sarepta scrutiny of surrogate (dystrophin) endpoints. This is the most bankable near-term value.
• WVE-006 (AATD): ~200k Pi*ZZ patients US+EU, no approved liver-directed therapy → genuine first-in-class, potentially high-value. The mid-2026 FDA accelerated-pathway feedback is the rNPV swing factor; positive feedback materially re-rates.
• WVE-007 (obesity): the largest TAM (~1B globally) but the most impaired probability after the weight-loss miss. rNPV now hinges on the add-on/maintenance positioning and Ph2a multidose — the market is implicitly pricing this option near zero, which is the asymmetry the bull case rests on.
• GSK programs: up to $2.8B milestones + low-teens royalties across 8 programs, cost-covered — pure non-dilutive optionality not in any P&L.

Brier forecast (the binary that matters): the cleanest scoreable proposition is the mid-2026 AATD regulatory pathway or the DMD NDA acceptance. Per --watchlist rules, no forecast.ts create is logged in this unattended loop — flagged here for Connor to log if he promotes this to a thesis. Suggested proposition: "WVE-N531 (DMD) NDA accepted for review by FDA by 2026-12-31" and "WVE-006 (AATD) receives a clear accelerated-approval pathway from FDA by 2026-09-30" — both p to be set on his own read.

Lens 12 · Bull vs Bear

Bull case. Wave is a multi-shot-on-goal RNA-medicines platform trading like a single failed obesity trial. (1) Platform validation is imminent and cheap to you here — first-in-class endogenous RNA editing (WVE-006) with FDA accelerated-pathway feedback mid-2026 is a category-defining proof-point the ~$1.2B cap barely credits. (2) A real near-term product — WVE-N531 DMD NDA in 2026 with best-in-class-to-date functional data (Time-to-Rise +3.8s, dystrophin 7.8%). (3) The obesity story isn't dead, it's repositioned — visceral-fat-specific loss + muscle preservation + twice-yearly dosing as a GLP-1 add-on/maintenance agent is a legitimate, large adjacency the market wrote to zero. (4) Funded to Q3 2028 with no debt — it can reach every catalyst without a gun-to-head raise. (5) GSK is a $2.8B-milestone, cost-covered call option plus a validating partner. Contrarian view of what the market refuses to see: the March crash conflated "WVE-007 is not a standalone GLP-1 killer" with "Wave's platform is broken" — those are different claims, and the second is unsupported by the editing/splicing data.

Bear case (2-3 permanent-impairment risks). (1) The platform's central premise — that stereopurity / endogenous editing yields clinically differentiated drugs — is unproven where it counts. Alnylam/Ionis/Arrowhead are commercial without stereopurity; if Wave's drugs are merely as good, the entire moat narrative collapses and Wave is a sub-scale also-ran. (2) Obesity, the only mass-market asset, just missed on the metric payers and patients buy (weight). "Body composition" is a harder commercial sell than a number on the scale; the add-on/maintenance pivot is a smaller, more crowded, more speculative market. (3) Serial dilution is structural — ~2x shares in 3 years, a live $250M ATM, and a business model that requires repeated equity issuance until (if) a product generates cash; every catalyst miss is funded by your ownership. Pre-mortem (18 months out, thesis broke): mid-2026 AATD FDA feedback was non-committal; the DMD NDA hit FDA's post-Sarepta surrogate-endpoint skepticism and stalled; WVE-007 Ph2a multidose still showed weak weight loss and the add-on data underwhelmed; cash drew toward 2028 and a dilutive raise hit a $4 stock. Are multiples too high? There's no earnings multiple — the question is whether ~$1.2B EV is too high for a pre-revenue platform with one near-term product and a damaged lead asset. Reasonable people split (analyst targets $13→$50); that dispersion is the trade.

Lens 13 · Devil's Advocate (short-seller)

Dismantling the bull case. What structurally breaks the way Wave "makes money"? It doesn't make money — that's the structural fact. Thirteen years, $1.35B accumulated deficit, no product, and revenue that is just GSK upfront amortization now running off. Revenue concentration: 100% GSK, and the most valuable piece (AATD) was just handed back, converting a partnered/funded asset into a self-funded liability. Why the moat is weaker than bulls think: stereopurity is a belief, not a demonstrated clinical edge — the commercial RNA leaders don't use it; "first-in-class RNA editing" is a timing lead measured in quarters that Korro Bio, ProQR, and well-capitalized big pharma can erase. Most dangerous competitor bulls underestimate: in obesity, Eli Lilly and Novo Nordisk (and the oral-GLP-1 / amylin pipelines) make WVE-007's "muscle-preservation add-on" a feature large players can simply bolt onto their own franchises; in DMD, Sarepta owns the channel and the exon-skipping playbook (and has dragged the whole surrogate-endpoint regulatory environment into scrutiny). Worst capital-allocation tells: relentless dilution, a director selling pre-readout (Rawcliffe, Jan 2026), de-partnering AATD into a cash-hungrier posture, and a CEO who is a GSK alumnus negotiating across the table from GSK. What must hold for today's ~$1.2B? That at least one of {AATD accelerated approval, DMD approval, obesity add-on} converts to a real product — i.e., the market is paying for a portfolio of options, several of which can (and historically, in biotech, often do) expire worthless. If growth/data disappoints 20-30%: there's no "growth" to disappoint — a single bad readout (as March proved) takes 50% off in a day; two more and you're at the Dec-2025-raise underwater zone with a dilutive raise into weakness. Single scenario that permanently impairs: AATD FDA feedback is lukewarm and the DMD NDA stalls on endpoint skepticism — the platform's "we can get to market" claim is falsified, the stock re-rates to cash, and the obesity option is the only thing left, priced as a long-shot. Plausibility: moderate, not remote — this is exactly why it trades where it does.

Lens 14 · Management Questions (ordered by information value)

1. After the INLIGHT 6-month <1% body-weight result, what is the explicit go/no-go bar for WVE-007 as a standalone agent vs. add-on/maintenance — and what multidose efficacy would you need to keep funding it?
2. On WVE-006 (AATD): what specifically did the FDA say about an accelerated-approval pathway, and what AAT-level / clinical endpoint would the agency need to see to grant it?
3. Why did you regain AATD rights from GSK rather than keep it funded/partnered — and how will you fund and partner a registrational AATD program alone without further dilution?
4. For WVE-N531 (DMD): given the FDA's heightened post-Sarepta scrutiny of dystrophin as a surrogate, what gives you confidence a 7.8% dystrophin + Time-to-Rise package clears the accelerated-approval bar in 2026?
5. What is your honest internal probability-of-success on each of the three lead assets, and how do you allocate the next $300M of burn across them?
6. The central platform claim is that stereopurity produces clinically differentiated drugs. What is the single best head-to-head clinical or preclinical evidence that stereopure beats stereorandom in humans, not in mice?
7. Extra-hepatic delivery (adipose/muscle/CNS) is preclinical. What is the timeline and the proof-point that converts free-uptake/SpiNA reach from a promise into clinical data?
8. With runway to Q3 2028 and a $250M ATM open, what would make you raise before then — and what would make you wait?
9. What are the GSK collaboration's near-term milestone triggers, and how much non-dilutive cash could the four selected programs realistically deliver in the next 24 months?
10. What is the realistic commercial profile of an obesity drug sold on body composition + twice-yearly dosing rather than scale weight — who prescribes it, who pays, and at what price?
11. How do you think about competitive obsolescence in RNA editing if Korro, ProQR, or a big-pharma editor reaches the clinic with a competitive AATD or PNPLA3 editor?
12. What does the Delaware redomiciliation change concretely — tax rate, the Singapore Section 34 patent exposure, governance — and what does it cost?
13. WVE-003 (HD) has compelling biomarker data but is gated on a strategic partner. What is the status of partnering discussions, and what happens to the program if no partner materializes in 2026?
14. Insider selling occurred ahead of the March readout. What is the board's trading-window and 10b5-1 policy, and how do you ensure alignment given the binary-catalyst nature of the stock?
15. Three-year horizon: what does Wave look like in 2029 — a commercial company with one approved drug, a perpetual platform-licensing shop, or an acquisition target — and which are you building toward?

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