scAAV.EF1a.miR26a.eGFP Plasmid
Generated by an autonomous AI research agent — Anthropic Claude Opus 4.7 or OpenAI GPT-5.5, max reasoning effort. Sources cited inline. Full disclosure at /methodology/jhtv-deep-dive.
Indication
hepatocellular carcinoma / liver cancer (miR-26a gene therapy)
Modality
Gene Therapy
Mechanism
AAV-delivered microRNA (miR-26a)
Target
miR-26a
rNPV Envelope
Low
-$45.4M
costs +25% · peak −25%
Base
-$35.4M
cumulative PoS 0.8%
High
-$25.5M
costs −25% · peak +25%
This is an explicitly hypothetical illustrative profile shown only for cohort consistency — the asset is an Addgene-distributed research plasmid, not a development candidate. Costs are anchored to the systemic-liver-AAV archetype (gene/cell preclinical $15-30M, biologic-grade Ph1-3) with a long preclinical phase reflecting the IND-enabling tox/CMC gap between a reporter-bearing research plasmid and a GMP clinical vector. PoS is deliberately depressed below generic gene-therapy medians because the only two clinical precedents for tumor-suppressor-miRNA replacement (MRX34, TargomiRs) both stalled on innate-immune toxicity; cumulative LoA ≈ 0.93% reflects that the in vivo efficacy evidence is a single 2009 mouse model with no clinical translation in 17 years.
Composite score breakdown
Locked rubric — 40/30/30 weights
Clinical relevance · 40%
0.70
Modality fit · 30%
0.74
Whitespace · 30%
0.50
Composite 0.652 — composite-score rank #15 of 50 top-tier inventions in the jhtv-portfolio@2026-Q2 cohort. The page header uses rNPV rank (#25) to match the index ordering.
Comparators
Real programs anchoring the engine inputs
MRX34 (Mirna Therapeutics / Synlogic legacy) — liposomal miR-34a mimic
The single closest mechanistic precedent: a tumor-suppressor-miRNA REPLACEMENT therapy (restore a miRNA lost in HCC), the exact therapeutic logic behind miR-26a. MRX34 is the cautionary anchor, NOT a live program — the Phase 1 (NCT01829971) in advanced solid tumors including HCC was halted in 2016 after five immune-related serious adverse events and four patient deaths, with only a 4% objective response rate (Hong et al., Br J Cancer 2020). It demonstrates both the regulatory pathway a clinical miR-26a product would have to traverse AND the dominant translational failure mode (innate-immune activation by exogenous miRNA payload) the JHU plasmid's mouse data did not surface.
Criteria 1 and 2: same mechanism class (tumor-suppressor miRNA replacement) and overlapping indication (HCC). Discontinued — retained only as a labelled cautionary precedent, not a live anchor.
TargomiRs / MesomiR-1 (EnGeneIC) — miR-15/16 mimic in EGFR-targeted EDV minicells
Second mechanism-class precedent: replacement of a lost tumor-suppressor miRNA (miR-16) delivered by a targeted vector. The MesomiR-1 Phase 1 (NCT02369198) in recurrent mesothelioma/NSCLC reached a 5×10^9 MTD with a 65% disease-control rate and one durable response, but also produced transient cytokine-release/rigor and liver-enzyme elevation, and the program has not advanced to a registrational study. It frames realistic early-clinical cost/duration for a miRNA-replacement modality and reinforces the innate-immune tolerability ceiling of exogenous miRNA payloads.
Criteria 1 and 4: same mechanism class (tumor-suppressor miRNA replacement) and comparable small-patient-population early-clinical economics. Inactive — cautionary archetype anchor for cost/duration only.
AAV-delivered hepatocyte gene therapy (AAV8/scAAV-to-liver) — archetype anchor
ARCHETYPE ANCHOR, not a product comparator. scAAV8 systemic hepatocyte transduction is the established delivery chassis the JHU plasmid is designed to produce. Liver-tropic AAV gene therapies (e.g. hemophilia AAV-FIX/FVIII programs) anchor preclinical/CMC cost and the dominant systemic-AAV delivery risks — neutralizing anti-AAV antibodies, hepatotoxicity/transaminitis, and durability — that any clinical miR-26a-AAV product would inherit. Used here only for cost-bound calibration of the illustrative envelope; it is NOT a same-target or same-indication comparator.
Criteria 4 archetype anchor only: same delivery modality (systemic liver-tropic AAV) for cost/risk calibration; explicitly NOT a product comparator (no same target, no same indication, no launched miR-26a equivalent).
Stage profile
Asset-specific cost, duration, and PoS by stage
| Stage | Cost | Duration | PoS | Citations |
|---|---|---|---|---|
| Preclinical | $25.0M | 36 mo | 30.0% | [0] [1] [5] |
| Phase I | $65.0M | 24 mo | 45.0% | [2] [3] [4] |
| Phase II | $140.0M | 36 mo | 22.0% | [2] [3] [4] |
| Phase III | $260.0M | 42 mo | 35.0% | [2] [3] |
| NDA/BLA Review | $18.0M | 12 mo | 80.0% | [2] |
Multiplier handling: No multipliers eligible for this asset under the locked methodology. See methodology for the rule.
Peak revenue and discount rate
$600.0M peak · WACC 18.0%
Peak revenue. This peak is an explicitly hypothetical illustrative figure for cohort-envelope consistency only — it is NOT a forecast. The asset is a research plasmid distributed openly via Addgene (#21894, a gift from the Mendell lab); JHU's realizable value is a non-exclusive biological-materials/reach-through arrangement or licensing of the underlying miRNA-replacement IP to a developer, not product revenue. If — hypothetically — a clinical miR-26a-AAV HCC therapeutic were ever developed by a licensee, an orphan-adjacent second-line HCC gene therapy might address a multi-hundred-million ceiling; $600M is a conservative placeholder anchored to that hypothetical, deliberately below blockbuster gene-therapy figures because no such program exists and the closest clinical precedents failed.
WACC. An 18% rate reflects research-tool-stage risk: there is no clinical candidate, the sole efficacy dataset is a 2009 mouse model, and both clinical precedents for the mechanism class (MRX34, TargomiRs) stalled on toxicity — risk well above a standard 12-14% biotech rate.
Sensitivity (tornado)
Top drivers of rNPV variance
Drivers ranked by absolute rNPV swing. The vertical tick inside each bar marks the base rNPV (-$35.4M); each bar spans the rNPV range produced by flexing one input between its low and high values. Gold = the input pushes rNPV up when increased; red = the input pushes rNPV down when increased.
Monte Carlo distribution
1,000 trials · rpNPV mode
This is a bimodal distribution by construction, not a Gaussian. Most paths terminate in clinical failure (red cluster — accumulated cost only); a minority succeed and capture full peak revenue (green tail). Bar heights are square-root-scaled so the success tail stays visible alongside the much taller failure cluster; exact counts are preserved in the percentiles below. Gold line = median (P50). Navy dashed = base rNPV (mean) — the probability-weighted expected value, which can sit above the median when the upper tail is strong enough to outweigh the failure cluster (and close to the median when it isn’t).
P5
-$112.7M
P25
-$46.8M
P50 (median)
-$22.1M
P75
-$13.4M
P95
-$7.0M
Prob ≥ 0
1.2%
Evidence register
6 per-assumption citations
| Assumption | Source | Date | Confidence |
|---|---|---|---|
Asset identity: research plasmid producing scAAV expressing miR-26a + eGFP reporter; sole in vivo evidence is the 2009 murine HCC model cmo_findings.asset_class_reality | Therapeutic microRNA delivery suppresses tumorigenesis in a murine liver cancer model (Kota et al., Cell 2009) peer_review | 2009-06-12 | high |
The exact plasmid is an openly distributed research reagent (a gift from the Mendell lab), not a proprietary clinical asset funding_path_archetype | Addgene Plasmid #21894 — sc AAV miR26a eGFP (deposited by Joshua Mendell lab) regulatory | 2015-03-24 | high |
Closest-mechanism clinical precedent (tumor-suppressor miRNA replacement in HCC) halted on immune toxicity — supports depressed clinical PoS stage_profile.phase_2.pos | Phase 1 study of MRX34, a liposomal miR-34a mimic, in patients with advanced solid tumours (Hong et al., Br J Cancer 2020) trial_disclosure | 2020-04-01 | high |
MRX34 program-halt corroboration (independent confirmation of discontinuation) comparators[0] | Mirna Therapeutics Halts Phase 1 Clinical Study of MRX34 news | 2009-06-12 | high |
Second mechanism-class precedent (miR-16 replacement, TargomiRs) reached Ph1 but did not advance — anchors early-clinical cost/duration and tolerability ceiling comparators[1] | EnGeneIC and ADRI Announce Results from MesomiR-1 Phase 1 Trial in Late Stage Mesothelioma news | 2015-08-25 | medium |
JHU public listing classifies the case under Research Tools > Vectors & Plasmids and frames it as a partnering/materials opportunity, not a clinical asset cmo_findings.asset_class_reality | JHU Technology Ventures listing — scAAV.EF1a.miR26a.eGFP Plasmid (Case C10912 / objectID 18740) regulatory | 2015-03-24 | high |
Thesis
Why this asset earns its rank
This asset is not a drug. It is scAAV.EF1a.miR26a.eGFP, a research-grade plasmid that produces a self-complementary AAV co-expressing microRNA-26a and an eGFP reporter, and JHU's own listing classifies it under Research Tools > Vectors & Plasmids. The same construct is openly distributed to the research community via Addgene (Plasmid #21894, a gift from the Mendell lab). Its scientific basis is strong and well cited: Kota et al. (Cell, 2009) showed that miR-26a is lost in hepatocellular carcinoma and that systemic scAAV8 delivery of miR-26a induced tumor-specific apoptosis and dramatic disease protection in a murine HCC model. But that is a 2009 mouse result and an enabling reagent — the eGFP reporter is the tell that this construct exists to study and visualize delivery, not to be dosed in patients. There is no clinical candidate, no IND, no GMP vector, and no defined patient population.
Because this is a research tool rather than a therapeutic asset, the rNPV is not the decision criterion here, which is why the asset is classified as grant_non_commercial; the engine envelope is shown only for cohort consistency. The closest real clinical precedents are mechanism analogs, not product comparators, and they are cautionary: MRX34, a liposomal miR-34a tumor-suppressor-replacement mimic, was halted in 2016 after four immune-related deaths in a Phase 1 that included HCC, and TargomiRs (miR-15/16 replacement) cleared Phase 1 but never advanced. Anchored to that mechanism-class reality and the systemic-liver-AAV delivery archetype, the engine result is -$45.4M to -$25.5M, with a base rNPV of -$35.4M and cumulative PoS of 0.8%; that spread is illustrative only — JHU's realizable value is non-exclusive materials distribution or out-licensing the miRNA-replacement IP to a developer that would still have to solve the innate-immune toxicity that sank the only clinical analogs.
Verdict: scientifically credible, commercially a research reagent. It earns rank 18 on the rubric's clinical-relevance and high gene-therapy modality_pos signal plus a neutral 'other'-indication whitespace, not on being a fundable standalone product — hence grant_non_commercial, because the value path is academic distribution and IP licensing, not equity-funded development.
Key risks
Asset-specific, not generic biotech risks
- Asset-class risk (dominant): this is an Addgene-distributed research plasmid with an eGFP reporter, not a clinical candidate — there is no IND, GMP vector, defined indication, or patient population, so any 'rNPV' is an illustrative cohort placeholder, not an investable forecast.
- Translational gap: the entire in vivo efficacy case rests on a single 2009 murine HCC study (Kota et al., Cell); 17 years later there is no clinical miR-26a-AAV program, which is itself evidence of how hard this translation has been.
- Mechanism-class toxicity: the two clinical precedents for tumor-suppressor-miRNA replacement — MRX34 (4 deaths, halted) and TargomiRs (stalled post-Ph1) — both ran into innate-immune activation; a clinical miR-26a-AAV product would inherit this risk, and miR-26a is broadly expressed in normal tissue, raising on-target normal-cell concerns the mouse model did not capture.
- Delivery risk inherited from the chassis: systemic scAAV8-to-liver carries pre-existing/treatment-induced neutralizing anti-AAV antibodies, hepatotoxicity/transaminitis, and durability limits — unaddressed in a reporter-bearing research plasmid.
- Funding-path risk: realizable value is non-exclusive materials distribution or IP out-licensing (royalties/milestones to a developer), not standalone equity — a VC modeling this as a fundable product is making a category error.