INO INO-3107

Recurrent respiratory papillomatosis · Inovio · BLA

Of 100 applications in this same position, about 40 get approved.

Until the FDA deadline25d

Base rate76%

Gap−36pts

PDUFA target date 2026-10-30the FDA may act earlier or later

Summary

We put approval of INOVIO's INO-3107 for recurrent respiratory papillomatosis at 40%, well below the ~76% base rate for small-company original applications. The main factor: in its filing letter the FDA said INOVIO had not justified eligibility for accelerated approval, and it has not publicly reversed that view. Since Precigen's PAPZIMEOS won full approval in 2025, INO-3107 must show a meaningful advantage over it. INO-3107's evidence is a 32-patient single-arm trial with a 28% year-1 complete response, against 51% for PAPZIMEOS. In its favour, the review is on track: late-cycle meeting and inspections are done, and labeling and confirmatory-trial feedback are expected. Confidence is low.

Recorded 2026-10-04 19:58 UTC · v1Proof ↓

Evidence · 5 items

Why 40%, not 76%

Indication

Adults with recurrent respiratory papillomatosis (RRP) caused by HPV-6 and/or HPV-11; filed under the accelerated approval program

76% of comparable applications were approved in the past: the opponent every forecast has to beat. Below are the reasons this forecast differs.

▲ supports approval, ▼ counts against it. More squares, more weight.

01▼ AgainstLarge In the filing letter the FDA said accelerated-approval eligibility had not been justified, and it has not withdrawn that view

In the December 2025 file-acceptance letter, the FDA noted as a potential review issue its preliminary conclusion that INOVIO had not provided adequate information to justify eligibility for the accelerated approval pathway. It also turned down priority review despite Breakthrough designation. At the July 2026 informal meeting the FDA did not discuss that comment, and it declined to comment on eligibility while the file is under review. INOVIO says it is not planning to seek traditional approval, which could require a Phase 3 trial. If the FDA keeps its preliminary view, a CRL is the most likely result.

Source: SEC 10-K filed 2026-03-12; 10-Q filed 2026-05-13; 8-K and 10-Q filed 2026-08-12
02▼ AgainstMedium A fully approved competitor raises the bar to 'meaningful advantage over available therapy', and the single-arm data are numerically weaker

Precigen's PAPZIMEOS received full approval for adult RRP in August 2025, with a 51% (18/35) complete response at 12 months. That makes it 'available therapy', and accelerated approval now needs a meaningful advantage over it. INO-3107's evidence is one single-arm Phase 1/2 trial (n=32) that compares each patient with their own prior year. Year-1 complete response (no surgery) was 28% (9/32); 81% had fewer surgeries. Year 2, from the retrospective follow-up RRP-002, was 50% (14/28). INOVIO argues the trials are not comparable: it counted every surgery from day 0, whereas 83% of PAPZIMEOS patients had debulking surgeries during dosing. It also argues neutralizing antibodies do not affect its DNA vector. Whether the FDA accepts these arguments is the central uncertainty.

Source: CGTLive / Precigen PAPZIMEOS approval coverage; The Laryngoscope 2025 (PMC12645365); INOVIO remarks at H.C. Wainwright conference, 2026-09-11
03▲ SupportsMedium Otherwise the review is proceeding toward an action: mid-cycle and late-cycle meetings are done, inspections are complete, and labeling and confirmatory-trial feedback are expected

The mid-cycle meeting (April 2026) raised no new significant issues. The late-cycle meeting is complete. All pre-licence inspections (clinical, manufacturing, device) are done, with a single reported observation that INOVIO says it has addressed. The FDA said its feedback on the confirmatory-trial design is forthcoming. INOVIO expected label negotiations to start in September 2026. As of 2026-10-04 we found no public confirmation that they began. The FDA working on confirmatory-trial design is a modestly positive sign for an accelerated-approval decision.

Source: SEC 8-K 2026-08-12; Q2 2026 earnings call 2026-08-12; H.C. Wainwright conference 2026-09-11
04▲ SupportsSmall Precedent in the same disease: CBER gave PAPZIMEOS full approval on a small single-arm trial

CBER has accepted surgery-free complete response from a roughly 35-patient single-arm trial as substantial evidence in RRP. So in principle the FDA could approve INO-3107 even with no randomized data. New CBER and OTP leadership since mid-2026 (Prasad left in April, the acting OTP director in June) granted INOVIO's informal meeting. Which way the new leadership leans is unknown.

Source: CGTLive PAPZIMEOS approval; STAT 2026-03-06 and 2026-06-29
05▼ AgainstSmall First commercial product of a small company: a drug-device combination with a prior device-manufacturing problem

INO-3107 combines a plasmid with the CELLECTRA 5PSP device. Plasmid supply comes from contract manufacturers; INOVIO's partners include Richter BioLogics and Kaneka Eurogentec. In 2024 a manufacturing defect in the device's single-use array delayed the BLA by about a year. Inspections are now complete with one observation, which limits this risk. INOVIO's cash runway runs only into Q1 2027, with going-concern language, so a CMC CRL would be hard for it to absorb.

Source: SEC 10-Q filed 2026-08-12 (going concern; CDMO supply agreements); INOVIO Q2 2024 results release (device array issue)

What would change this forecast

01
INOVIO confirming that label negotiations or post-marketing requirement and confirmatory-trial discussions with the FDA are under way (up)
02
Any statement that the FDA has resolved, or reiterated, its preliminary view on accelerated-approval eligibility
03
A PDUFA extension after a major amendment, for example new comparative analyses against PAPZIMEOS (date change only, mildly informative)
04
A Form 483 response problem, or a device or CMC information request disclosed late in the review (down)

Any change is published as a new version; earlier versions stay exactly as they were.

Confidence

Low

Manufacturing and inspection risk

Medium

This is the company's first commercial product: a plasmid DNA medicine made at contract manufacturers and delivered by a proprietary electroporation device, which had an array-manufacturing defect in 2024. All pre-licence inspections are complete with one reported observation, so CMC is secondary to the question of accelerated-approval eligibility.

Record · version 1

Written on 2026-10-04, 26 days before the PDUFA target date.

Timeline

Versions

v1 2026-10-04 19:58 UTC 40% Current version JSON ↓.ots ↓ ○ Timestamp submitted, awaiting block confirmation

Fingerprint

SHA-25674c54972dd1b8814daa938a76d746d06cfeb18c9a86fcab65670f90e583712ab

The fingerprint of the v1 file. It is what the timestamp commits to: change one character of the file and the fingerprint no longer matches.

Verify it yourself

Download the JSON file above and the .ots file of the same name into one folder.
Compute the SHA-256 of the file. It should match the fingerprint above.
Verify with OpenTimestamps. Once the timestamp is in a Bitcoin block, ots verify reports the block time if you run a Bitcoin node; without one, drop both files on the verifier at opentimestamps.org, or run ots info to see the block height and look it up in any block explorer. If the block time is before the FDA’s decision, the file cannot have been written afterwards.

pip install opentimestamps-client
shasum -a 256 v1_20261004T195802Z.json
ots verify v1_20261004T195802Z.json.ots
ots info v1_20261004T195802Z.json.ots

Scoring rule

What is scored is the last version recorded at least 2 days before the PDUFA target date; if the FDA decides early, only versions recorded before the day of its decision count. For this forecast the cutoff is 2026-10-28. Its error (also called the Brier score) is the squared distance between the forecast and the outcome, set against the error of quoting the base rate only.