Tune Therapeutics

Phase A — Understand the business

Lens 1 · Company Overview

Tune Therapeutics is an epigenome-editing company — it changes how loudly a gene is expressed without cutting or rewriting the DNA sequence. Founded December 2021, spun out of Duke University (Charles Gersbach's lab) and the Innovative Genomics Institute (Fyodor Urnov), and jointly headquartered in Durham, NC (300 Morris St) and Seattle, WA (1930 Boren Ave) with ~85 employees split roughly evenly between the two sites. It is a Duke OTC startup.

The product is the platform: TEMPO. TEMPO ("Tuneable Epigenetic Modulation Platform") is a modular system — a DNA-binding domain (a catalytically-dead CRISPR/dCas9 that binds but does not cut) tethered to one or more effector proteins that deposit or remove epigenetic marks (methylation, chromatin repression), dialing a target gene up or down. The pitch: the durability of gene editing without the double-strand breaks, permanence, and off-target-cut risk of Cas9 nucleases. This expands the addressable disease set from rare monogenic disorders (where editing lives) toward common, chronic, and age-related disease — the company's explicit ambition.

Business model. Classic platform biotech: a broad enabling technology, monetized by (a) advancing a wholly-owned lead asset (TUNE-401) to proof-of-concept and value inflection, then (b) partnering/out-licensing platform applications across therapeutic areas. No revenue today; the asset is the company.

Lead asset — TUNE-401 (chronic hepatitis B): a first-in-class epigenetic silencer — dCas9 fused to two epigenetic effector domains (a methyltransferase + a chromatin repressor), encoded as mRNA + guide RNA, packaged in a liver-targeting lipid nanoparticle (LNP) licensed from Acuitas Therapeutics, targeting a conserved "master controller" sequence shared by both integrated HBV DNA and the cccDNA reservoir.

Customers / suppliers / competitors. No commercial customers (pre-revenue). Key supplier: Acuitas Therapeutics (the LNP — the same delivery lineage behind the COVID mRNA vaccines). End "customer" is ultimately the ~250–300M chronic-HBV population via a future pharma partner/payer. Competitors: GSK/Ionis (bepirovirsen) and the siRNA field on the HBV product axis; nChroma Bio, Epicrispr, Chroma/Sangamo on the epigenome-editing platform axis (Lens 3).

Lens 2 · Supply Chain

For a clinical-stage in-vivo genetic medicine, the "supply chain" is the manufacture-and-deliver stack for the drug plus the clinical-execution chain:

• Upstream IP / discovery → Duke (Gersbach lab foundational patents, licensed via Duke OTC) + IGI/Berkeley (Urnov) + internally developed and in-licensed effector components.
• Drug substance: mRNA (dCas9 + effector fusion) + synthetic guide RNA — produced by CDMO in-vitro transcription (specific CDMO not disclosed — n/a — private, not disclosed).
• Delivery vehicle — the chokepoint: Acuitas Therapeutics LNP. This is a single-source dependency and the most important named node in the chain: hepatocyte tropism, tolerability, and re-dosability all ride on the LNP, and Acuitas licenses to many players (Pfizer/BioNTech lineage), so terms and exclusivity matter. A functional cure that requires repeat dosing (the trial uses up to 3 infusions) leans harder on LNP tolerability than a one-shot editor would.
• Clinical execution → CROs plus a geographically unusual trial footprint: New Zealand, Hong Kong, Moldova. New Zealand (Medsafe CTA) and Hong Kong are hepatology-strong, high-HBV-prevalence, fast-start jurisdictions; the notable absence is a US FDA IND — first-in-human ran offshore (Lens 10 / Lens 13 flag).
• Named human nodes: PI Prof. Ed Gane (University of Auckland / Auckland City Hospital — one of the most cited HBV-cure clinicians globally) and Prof. Man-Fung Yuen (University of Hong Kong). Landing Gane + Yuen as investigators is itself a credibility signal — these are the people GSK, Vir, and Arbutus also use.

Chokepoints: (1) Acuitas LNP single-source; (2) redosing tolerability; (3) manufacturing scale for a 250M-patient indication is undemonstrated and undisclosed. Names present → lens satisfied.

Lens 3 · Competitive Advantages (moats)

The platform moat — real but young. Tune's durable moat candidates:

1. Founder-IP / know-how. Gersbach and Urnov are two of the field's most-cited genome/epigenome engineers; the Duke-licensed estate + internal effector engineering is the raw moat. Epigenome editing is a craft — which effector domains, in what geometry, with what guide, deposited how durably — and that tacit knowledge is hard to replicate.
2. Clinical lead-time (the strongest current moat). As of mid-2026 Tune has the only in-clinic human proof-of-concept for durable epigenetic silencing of a disease target — a genuine first. Competitors (nChroma, Epicrispr, Sangamo) are pre-clinical or just filing CTAs. That 12–24-month lead in a hot field is the asset VCs are paying for.
3. Redosable, non-permanent mechanism. Because TEMPO makes no cut and no permanent sequence change, the epigenetic state is (in principle) reversible and re-dosable — a safety moat vs. permanent editors, and an argument for a broader chronic-disease franchise. (The same reversibility is the bear case — see Lens 13.)

Bargaining power. As a private pre-revenue biotech, Tune has low bargaining power over suppliers (Acuitas holds the LNP) and over a future commercial partner — until TUNE-401 Phase 2 data de-risk the platform, at which point a single positive readout flips the negotiating table. Its power over capital is currently high (tier-1 syndicate oversubscribed the Series B — Lens 7 private).

Ground-truth caveat: the commercial-layer files for genomics (positioning.md, bottlenecks.md) are missing, so the moat read is web-derived, not compiled.

Lens 4 · Segments

Not applicable in the operating sense — no revenue, no reportable segments. Per the +clinical overlay, the "segments" are pipeline programs / therapeutic verticals:

segments.csv is empty; revenue/EBITDA-by-segment is n/a — pre-revenue. The concentration reality: essentially 100% of near-term enterprise value sits in TUNE-401. The PCSK9 program is the platform-validation story (and a template for a fast-follow / partnering asset), but it is not the value driver on a 1–2 year horizon.

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Phase B — Measure performance

Lens 5 · Funding & Valuation Trajectory (private overlay — replaces Earnings Result) + Pipeline-by-Phase (clinical overlay)

Funding trajectory — all ``, unaudited:

. Note the $175M vs $180M discrepancy across outlets and the ~$900M valuation figure (salestools.io citing the round) — I flag both rather than pick one; the primary press release stated only "over $175M" and did not disclose a valuation.

Investor-quality read: the syndicate is a strong tell. Regeneron Ventures (strategic pharma, not just financial) and Hevolution Foundation (the Saudi-backed, ~$1B/yr aging-science funder) both anchoring signals that (a) a big-pharma strategic wants a window on the platform and (b) the longevity/chronic-disease framing is landing with deep-pocketed patient capital. No crossover-fund (Fidelity/T. Rowe/Coatue) entry yet → this is not an IPO-proximate cap table; it is a mid-stage private (Lens 7 private).

Burn signal: $222M raised, ~85 staff, one asset in Phase 1b/2a plus a preclinical engine → this is a capital-intensive platform burn. The Series B was explicitly to fund TUNE-401 trials and pipeline; on typical clinical-biotech burn ($60–100M/yr at this scale, ``), the Series B buys roughly ~2–3 years of runway to the Phase 2 inflection (Lens 11).

Pipeline-by-phase — TUNE-401 (the asset that is the company):

Lens 5-clinical · The TUNE-401 EASL 2026 result (the "earnings print" for a clinical-stage name)

The Phase 1b/2a proof-of-concept, presented as a late-breaking oral at EASL 2026 (Barcelona, May 2026) — trial TUNE-401-001, the "print" that matters most:

• Design: Single-Ascending-Dose (4 levels: 0.2 / 0.45 / 0.65 / 0.85 mg/kg) + Multiple-Dose (up to 3 infusions of 0.65 mg/kg, ≥4 weeks apart). Sites in New Zealand, Hong Kong, Moldova.
• cccDNA silencing (the headline — first-ever in humans): 4 of 7 HBeAg(-) patients at dose levels 3–4 lost pgRNA (a direct cccDNA-transcription biomarker); 3 of those 4 also lost HBcrAg; all pgRNA-loss patients turned P-HBcAg negative; 3 of 5 HBeAg(+) patients at DL3–4 lost HBeAg. Separately reported: up to 98% reduction in a lead patient and "four people who have become biomarker negative".
• Depth / consistency: "durable, dose-dependent repression across all biomarkers in 100% of participants at dose levels 2–4".
• Durability: repression observed to 17 months post-single-dose — the single most important number in the dossier, because it directly rebuts the field's central skepticism (Lens 13).
• Safety: mild-to-moderate infusion-related reactions + transient asymptomatic transaminase elevations (normalizing within days); no additive toxicity across multiple doses. No serious safety signal disclosed.
• Next: larger Phase 2, expanded multi-dose cohorts + dose optimization, initiation as early as late 2026.

Analyst read: for a Phase 1b/2a, this is a strong, differentiated signal — direct biomarker evidence of cccDNA silencing (which nucleos(t)ide analogs cannot touch) with >1-year durability from a transient dose. It is early, small-n, offshore, and single-arm; but it is exactly the result the platform needed. CEO McHutchison — a 30-year hepatologist — called one slide "the most dramatic … I've seen in 20 years". Discount the founder's enthusiasm; keep the biomarker matrix and the 17 months.

Lens 6 · Founder / Management Communications (private overlay — replaces Earnings Calls)

No earnings calls. The "sentiment" signal is the cadence and confidence of scientific communications, which has escalated on a clean upward slope:

• 2021 launch → platform vision, no assets in clinic.
• 2023 (ASGCT/HepDART) → NHP PCSK9 durability (9+ months, later ~2 yr) + human-chimeric-liver-mouse HBV data (90–95% repression, 550+ days across 275+ cell divisions).
• 2025 (Series B) → capital + CEO transition; framing shifts from "platform" to "clinical-stage company."
• 2026 (EASL late-breaker) → first human PoC; management tone moves from promising to "clinical signal this clear I've rarely seen".

The tone has shifted from platform-promissory to asset-confident, and — critically — the confidence is now backed by human biomarker data, not just NHP/mouse. The thing they stopped hedging: whether epigenetic silencing survives in dividing human hepatocytes in vivo. The thing they still don't say: HBsAg seroclearance / off-treatment functional-cure rates in a controlled setting — the bar GSK is clearing (Lens 7/13).

Lens 7 · Catalyst Calendar + Cap-Table / Comps (clinical + private overlays)

Multiples comps: n/a — private, pre-revenue, no multiples. Do not fabricate. The right comps are (a) by mechanism/indication and (b) by cap-table quality.

Mechanism / HBV-cure comps (the competitive field):

The comp that matters: Tune is ~1–2 years behind GSK on the HBV product timeline but years ahead of every other epigenome editor on the platform timeline. It is simultaneously a laggard in HBV and the leader in epigenetic silencing. Which frame wins the valuation depends entirely on whether the mechanism (durable cccDNA silencing) proves differentiated enough vs. GSK's already-approved-pathway ASO (Lens 12/13).

Cap-table quality: NEA (lead, both rounds), Regeneron Ventures (strategic), Hevolution (aging capital), Yosemite, Pappas, Duke Capital Partners. Tier-1, strategically diverse, no crossover funds yet → healthy but not IPO-imminent.

Catalyst calendar:

Lens 8 · Value-Moving Events (private overlay — funding/data events, not stock)

No stock; the events that have re-rated the private mark:

1. Dec 2021 launch (+$40M A) — platform stood up.
2. May 2023 NHP PCSK9 durability — first "therapeutically relevant, durable" epigenetic repression in primates; the platform-credibility unlock.
3. Jan 2025 Series B ($175M+ at ~$900M) + CEO transition to John McHutchison — capital + a marquee hepatology operator; the "this is a real drug company now" re-rate.
4. May 2026 EASL human PoC — the biggest value event: first-in-human durable cccDNA silencing. This is what a future round/partnership will be priced off. Pattern: this name re-rates on data credibility milestones and marquee-hire/strategic-investor signals, not macro — exactly what you'd expect for a platform biotech pre-IPO.

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Phase C — Judge people & books

Lens 9 · Management

• CEO & Chairman — John McHutchison, AO, MD (appointed CEO Mar 2025; board member since Jan 2023). This is the single most important asset after TUNE-401's data. Former Chief Scientific Officer / Head of R&D at Gilead Sciences, where he led development of Gilead's liver-directed franchise (the sofosbuvir/HCV functional-cure era that actually cured hepatitis C) and was involved in the transformative Kite (CAR-T) acquisition. A hepatologist who has already taken a viral-hepatitis cure to global approval running an HBV-cure company is the highest-quality domain fit imaginable. Track record: elite, quantified, directly on-point.
• Founder / President / CFO / COO — Akira Matsuno — ex-Juno Therapeutics and Lyell Immunopharma (cell-therapy finance/ops pedigree). Skin in the game as founder.
• CSO — Derek Jantz, PhD — co-founded Precision BioSciences (2006) and led allogeneic CAR-T + in-vivo editing there. Deep gene-editing translational chops; note the Precision BioSciences lineage runs through Tune (Jantz; earlier CEO Matt Kane was also ex-Precision) — a Durham/Duke gene-editing mafia.
• Scientific co-founders — Charles Gersbach (Duke) and Fyodor Urnov (Berkeley/IGI) — two of the most-cited names in genome/epigenome engineering; Urnov literally co-coined "genome editing." KOL credibility is top-decile for the field.
• Founder → professional-manager transition, executed well. The 2025 handoff from founder-operator (Kane) to an industry heavyweight (McHutchison) at exactly the clinical-stage inflection is a textbook, positive governance signal — the opposite of founder-can't-let-go.

Capital allocation: ~$222M raised, concentrated into one lead asset + a disciplined preclinical engine, with a strategic (Regeneron) and a mission-aligned (Hevolution) investor. No value-destruction signals visible. Red flags: none material found — the only structural note is heavy Precision BioSciences / Duke interconnection (related-network, not related-party).

Lens 10 · Forensic Red Flags + Regulatory Findings

Accounting forensics: n/a — private, unaudited, no financial statements disclosed. There is no income statement, balance sheet, or cash-flow statement to interrogate; revenue-recognition/SBC/goodwill analysis does not apply to a pre-revenue private. The financial "red flag" surface is therefore burn vs. runway (Lens 11) and round-to-round dilution (unquantified — n/a — not disclosed).

Regulatory findings:

• SEC (EDGAR EFTS — LR + AAER): 0 findings. Tune has no CIK and is not an SEC filer — no enforcement search is possible; total_sec_findings: 0.
• Non-SEC (web search — FTC/DOJ/FDA/consent-decree/settlement/penalty): no material enforcement, litigation, or penalty hits found for "Tune Therapeutics" as of 2026-07-06.
• IP / patent litigation: no Tune-specific patent dispute found. The company sits near the broad CRISPR-Cas9 patent estate (Broad vs. Berkeley), but its dCas9-based epigenetic-editing IP derives from Duke (Gersbach) via Duke OTC license and internal work; no active Tune-named IP litigation surfaced. Latent risk: the entire Cas9 field is exposed to the unresolved Broad/Berkeley estate (Lens 13).
• Item 3 (Legal Proceedings): n/a — no 10-K exists (private).
• Verdict: No material regulatory or legal findings — verified via SEC EDGAR EFTS (LR, AAER, 0 hits), web search, and (no 10-K Item 3 available) as of 2026-07-06.

The real "forensic" flags for this name are clinical, not accounting (per +clinical re-point): (1) small-n, single-arm, offshore Phase 1b/2a — no controlled comparator; (2) biomarker endpoints (pgRNA/HBcrAg/HBeAg), not the regulatory endpoint (off-treatment HBsAg seroclearance) — the leap from biomarker to functional cure is unproven; (3) no US FDA IND yet disclosed — a US pathway is a future gating item.

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Phase D — Project & stress-test

Lens 11 · IPO-Readiness / Runway-to-Catalyst + rNPV (private + clinical overlays — replaces Forward Projection)

No EPS projection — pre-revenue. Two questions replace it: (a) does cash reach the next value-inflection catalyst? and (b) what is the lead asset worth, risk-adjusted?

Runway-to-catalyst ``: Series B (>$175M, Jan 2025) + residual A, against ~85 staff and one Phase 1b/2a → clinical-biotech burn of ~$60–100M/yr implies runway into ~2027–2028 — enough to initiate Phase 2 (late 2026) and likely reach a Phase 2 interim readout, which is the inflection. Judgment: funded to the catalyst that matters, with a raise likely around the Phase 2 data to fund pivotal work. The gating risk is not near-term insolvency; it is what the Phase 2 data say.

rNPV of TUNE-401 (lead asset), illustrative `` — every input labeled:

• CHB therapeutics market: ~$3.2B across 7MM by 2034; US CHB sales ~$710M in 2024.
• Peak-sales assumption for a differentiated durable functional cure capturing a slice of a cure-driven market: ~$1.0–1.5B risk-unadjusted peak.
• Probability of success from Phase 1b/2a (infectious disease, positive PoC but pre-pivotal): ~15–25%.
• rNPV (peak × PoS × discount, single asset): order-of-magnitude ~$0.3–0.6B `` — which, notably, is below the reported ~$900M Series-B mark, i.e. the private valuation already prices in platform optionality (PCSK9, CAR-T, aging), not just TUNE-401. That gap IS the thesis: you are underwriting the platform, not the HBV asset alone.

Be-early / IPO-readiness read (Tune is absent from private-watch.json — supplying it):

• Stage: mid-stage private (Series B, ~$900M) — ipo_readiness: 2–3 (growth→approaching late-stage). Not pre-IPO: no crossover funds, single asset only just past PoC.
• Milestones that unlock an S-1: (1) TUNE-401 Phase 2 interim showing off-treatment HBsAg loss (biomarker→cure); (2) a second program IND (PCSK9) to prove the platform isn't a one-asset story; (3) a crossover round (Fidelity/T. Rowe/Coatue) — the classic 12–18-month-to-IPO tell; (4) ideally a pharma platform deal (Regeneron already on the cap table is the obvious counterparty).
• Estimated tradeable window: not before 2027–2028, and contingent on Phase 2 + a crossover round. (Recommend adding a tune-therapeutics entry to research/private-watch.json — beat: genomics, stage: growth, ipo_readiness: 2, lead_investors: NEA/Regeneron/Hevolution, catalyst: "TUNE-401 Ph2 cccDNA-silencing → functional-cure readout 2027", dossier: this file. Deferred here per wave boundaries — flagged for Connor.)

No forecast.ts create logged — per --watchlist rule (log a Brier forecast only on genuine commitment; and this is a private with no clean binary yet). The forecast to log at Phase 2 initiation: "TUNE-401 Phase 2 interim shows ≥1 patient with off-treatment HBsAg seroclearance, resolves 2027-12-31, p≈0.4."

Lens 12 · Bull vs Bear

Bull case. Tune owns the first and only human clinical validation that you can durably silence a disease-driving genomic element epigenetically, without cutting DNA — and it showed >1-year durability from a transient dose in the exact setting (dividing hepatocytes, cccDNA) where skeptics said epigenetic silencing would wash out. That is a platform "PCSK9 moment": if cccDNA silencing translates to off-treatment functional cure in Phase 2, TUNE-401 is a multi-billion-dollar HBV asset and every subsequent TEMPO program (PCSK9, immuno-oncology, aging) inherits de-risked, redosable, reversible in-vivo silencing — a franchise, not a drug. It is run by the hepatologist who already delivered the HCV cure at Gilead, funded by a strategic (Regeneron) and aging capital (Hevolution), with the field's top KOLs as founders and investigators. The secular tailwind — epigenome editing is the hottest post-CRISPR frontier — means platform optionality is worth more than the sum of programs.

Bear case (permanent-impairment risks). (1) The mechanism might be durable-but-not-durable-enough. Published work shows epigenetic-silencing durability "varies widely across target genes" and can be reversed by targeted demethylation. HBV cccDNA in a chronically re-seeding, immune-pressured liver is a harder, longer test than 17 months in a Phase 1 — if silencing relapses off-drug at scale, the "cure" collapses into "another suppressive therapy," and suppressive therapy already exists (cheap nucleos(t)ide analogs). (2) GSK gets there first with an easier modality. Bepirovirsen (ASO) has a Phase 3 functional-cure readout, Breakthrough/Priority Review, and a ~Q3 2026 FDA decision — a first-mover functional cure via a simpler, non-genetic-medicine platform that payers and regulators already understand. Tune must prove superiority or differentiation, not just efficacy. (3) Single-asset concentration + offshore, small-n, biomarker-endpoint data — the ~$900M mark prices platform optionality that is still preclinical; a Phase 2 miss impairs the whole company, not one program.

Pre-mortem (it's 18 months out, the thesis broke): the Phase 2 shows deep biomarker suppression on-drug but HBsAg rebounds off-treatment as cccDNA re-methylation dilutes through hepatocyte turnover — durability that looked like a cure in Phase 1 proves to be durable suppression. Simultaneously GSK's bepirovirsen is approved, resetting the bar to "off-treatment cure or nothing." The private mark compresses, the crossover round doesn't come, and Tune pivots to positioning TEMPO as a platform-partnering company rather than a lead-asset developer.

Are multiples too high? No public multiple exists; the ~$900M private mark is rich relative to single-asset rNPV (~$0.3–0.6B ) and only justified by platform optionality — reasonable for a hot-field platform with human PoC, but it leaves no margin for a Phase 2 disappointment.

Contrarian view (what the market refuses to see): the consensus frames HBV as "GSK's race to lose." The thing being underpriced is that cccDNA silencing and HBsAg knockdown are mechanistically different bets — bepirovirsen lowers the antigen; Tune tries to switch off the reservoir that makes it. If durability holds, Tune isn't competing with GSK's 19% — it's targeting the patients bepirovirsen doesn't cure, and doing it re-dosably. The 17-month durability datapoint is more important than the market has priced, precisely because it's the one thing everyone assumed epigenetic editing couldn't do.

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

Dismantling the bull case:

• The whole thesis rests on a durability extrapolation the science says is gene-dependent. "17 months in ~7 patients" is being asked to underwrite "lifelong cure in millions." Peer-reviewed epigenome-editing literature explicitly warns durability varies by locus and is reversible. The single most dangerous slide in the deck is the one management is proudest of.
• The endpoint gap is doing a lot of work. pgRNA/HBcrAg/HBeAg loss ≠ HBsAg seroclearance ≠ off-treatment functional cure. Regulators (and GSK's bar) require the last one. Biomarker theater has killed many HBV programs.
• Most dangerous competitor bulls underestimate: not another epigenetic editor — it's GSK/Ionis with an already-de-risked, non-viral-vector ASO that regulators are about to bless. If the first HBV functional cure is a quarterly injection with a known safety class, a first-in-class LNP-delivered epigenetic editor requiring infusion-reaction management and offshore-only data faces a steep payer/prescriber-adoption and safety-scrutiny hill.
• Concentration: ~100% of near-term value in one offshore-tested asset; the platform's other "validations" (PCSK9, CAR-T) are preclinical and could equally reveal the durability problem.
• Capital-allocation / structure: none egregious, but the ~$900M mark is a VC construct, not a market clearing price — the "valuation" is exactly the kind of number that resets 40–60% in a down biotech tape or a Phase 2 stumble. No crossover fund has validated it.
• What must hold for the ~$900M: durable off-treatment cccDNA silencing at scale and platform breadth and a benign safety profile on repeat LNP dosing and a defensible IP position against the CRISPR estate. That's a four-part conjunction on a single Phase-1 dataset.
• 20–30% disappointment scenario: if Phase 2 off-treatment durability disappoints by even a modest margin, the asset degrades from "cure" to "another suppressive," rNPV falls toward the low end, and the platform premium evaporates → plausible 50%+ private markdown.
• The single scenario that permanently impairs: off-treatment relapse of HBsAg in Phase 2 driven by cccDNA re-methylation loss through hepatocyte turnover. Plausibility: moderate — the exact failure mode the field has flagged, only partially rebutted by 17 months of Phase 1 data.

Lens 14 · Management Questions (ordered by information value)

1. In the Phase 1b/2a, what happened to HBsAg and the biomarker panel off treatment — and for how long after the last dose did silencing hold before any rebound?
2. What is the mechanistic evidence that epigenetic marks on cccDNA survive hepatocyte turnover in a chronically infected liver, versus dilute out over time?
3. What is the Phase 2 primary endpoint — off-treatment HBsAg seroclearance, or a biomarker — and what off-drug durability window defines success?
4. How does TUNE-401's target product profile differentiate against GSK's bepirovirsen if it's approved in 2026 — superiority, combinability, or a distinct patient segment?
5. What is your US FDA IND status and timeline, and why did first-in-human run in New Zealand/Hong Kong/Moldova rather than under a US IND?
6. On what terms is the Acuitas LNP licensed — exclusivity for HBV/liver, field limitations, royalty stack — and what is the single-source-supply mitigation?
7. What re-dosing frequency does a durable functional cure actually require, and what is the cumulative safety picture (infusion reactions, transaminases) over repeat LNP dosing?
8. What is your freedom-to-operate position relative to the Broad/Berkeley Cas9 estate and other epigenome-editing IP?
9. What is current cash runway, and what milestone do you intend to fund to before the next raise?
10. Which is the second program to an IND, on what timeline, and why that indication — what does it prove about platform breadth?
11. What are the manufacturing and COGS economics of an mRNA/gRNA-in-LNP product at the scale a 250M-patient indication implies?
12. What durability/off-target data across multiple target genes (not just HBV) do you have to show the silencing is generalizable, not locus-lucky?
13. Is a pharma platform partnership (e.g. Regeneron) contemplated, and how do you value platform-out-licensing vs. wholly-owned development?
14. What insider/employee ownership and retention structure exists post-CEO-transition, and how is the founding scientific team incentivized to stay?
15. What is the capital plan to commercialization — how much more capital, and via what mix of private rounds, partnership, or IPO?

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