Phio Pharmaceuticals Announces Positive Pathology Results: Final Maximum Dose Cohort for INTASYL PH-762 Skin Cancer Trial

Rhea-AI Summary

Phio Pharmaceuticals (NASDAQ: PHIO) reported pathologic results from the fifth and final dose cohort of its Phase 1b INTASYL PH-762 trial in cutaneous carcinomas on November 3, 2025. In the three patients completing the cohort, one had 100% tumor clearance, one had >90% clearance, and one had >50% clearance, with assessments at approximately 5 weeks after initial injection. To date, 18 patients have completed treatment across five cohorts, including 6 complete responses among 16 cSCC patients. The Safety Monitoring Committee reviewed safety at the maximum dose and found no dose-limiting toxicities; overall the trial reports no clinically relevant treatment-emergent adverse effects and dose escalation reached ~20-fold versus cohort 1. Trial identifier: NCT# 06014086.

Positive

• 1 of 3 patients: 100% tumor clearance (~5 weeks)
• Cumulative cSCC: 6 complete responses in 16 patients
• No dose-limiting toxicities reported across treated patients
• SMC confirmed safety at ~20-fold maximum dose versus cohort 1

Negative

• 18 patients completed treatment — limited sample size for efficacy conclusions
• Six cSCC and one metastatic melanoma patient had non-response <50% clearance

Insights

Clinical development analyst

Phase 1b intratumoral PH-762 shows strong early pathological activity and an unchanged safety profile at the maximum tested dose.

The dataset reports pathologic clearance of 100% in one patient, >90% in a second, and >50% in a third in the fifth and final dose cohort, with pathologic assessment performed at approximately 5 weeks after the first injection. Across 18 treated patients, the cumulative results in 16 cutaneous squamous cell carcinoma cases include six complete responses, two near complete responses, and two partial responses; one metastatic Merkel cell carcinoma patient had a partial response; six cSCC and one metastatic melanoma were non-responders. No patients have shown clinical progression and no dose-limiting toxicities or clinically relevant treatment-emergent adverse effects were observed at the maximum dose; dose escalation reached roughly a 20-fold increase versus the first cohort.

These facts describe a clear signal of intratumoral anti-tumor activity plus a reassuring safety readout in a small Phase 1b cohort. Key dependencies remain strictly factual: confirmation of these responses across larger numbers, durability beyond the 5 weeks pathology timepoint, and whether additional screening/treatment in the fifth cohort changes the response mix. Concrete items to watch include additional patient enrollments in the fifth cohort, any later pathological assessments beyond 5 weeks, and formal safety summaries as more patients complete follow-up; expect these updates in the near term as the study continues.

Pathologic Clearance: 100% Tumor Clearance (Complete Response) in One Patient, Greater than 90% (Near Complete Response) in Second Patient, Greater than 50% (Partial Response) in Third Patient

Pathologic Results Assessed at Approximately 5 Weeks

Safety Monitoring Committee Issues Favorable Review of Safety Data at the Maximum Dose

King of Prussia, Pennsylvania--(Newsfile Corp. - November 3, 2025) - Phio Pharmaceuticals Corp. (NASDAQ: PHIO) is a clinical-stage siRNA biopharmaceutical company developing therapeutics using its proprietary INTASYL^® gene silencing technology to eliminate cancer. Phio announced today the pathologic results for three patients with cutaneous squamous cell carcinoma (cSCC) who completed treatment in the fifth and final dose cohort of Phio's on-going Phase 1b dose escalation trial: 100% tumor clearance in one of three patients, > 90% clearance in the second patient, and > 50% clearance in the third patient.

To date, a total of 18 patients with cutaneous carcinomas have completed treatment across five dose escalating cohorts in the Phase 1b trial. The cumulative pathologic response in 16 patients with cSCC include six with a complete response (100% clearance), two with a near complete response (> 90% clearance) and two with a partial response (> 50% clearance). A single patient with metastatic Merkel cell carcinoma had a partial response (> 50% clearance). Six patients with cSCC and one patient with metastatic melanoma had a pathologic non-response (< 50% clearance). No patients in the study have exhibited clinical progression of disease. Phio may continue to screen and treat additional patients as part of the fifth cohort.

The trial is designed to evaluate the safety and tolerability of neoadjuvant use of intratumoral PH-762 in Stages 1, 2 and 4 cutaneous squamous cell carcinoma (cSCC), Stage 4 melanoma, and Stage 4 Merkel cell carcinoma (NCT# 06014086). Per the trial's protocol, patients receive four injections of PH-762 at weekly intervals and pathologic response is assessed approximately 5 weeks after the initial injection of PH-762.

"The encouraging outcomes of intratumoral PH-762 in patients who have received treatment thus far is a significant step in clinical development and highlights the promise of a viable non-surgical alternative treatment for cutaneous carcinomas," said Robert Bitterman, CEO and Chairman of Phio Pharmaceuticals.

In addition, the Safety Monitoring Committee (SMC) completed its pre-specified review of safety results for the first three patients in the fifth cohort and confirmed that there were no dose-limiting toxicities or clinically relevant treatment-emergent adverse effects at this maximum dose concentration. Further, there have been no dose-limiting toxicities or clinically relevant treatment-emergent adverse effects in any of the patients who have completed treatment with intratumoral PH-762 in this trial.

"We are pleased with the continuing safety profile of PH-762 throughout dose escalation to approximately a 20-fold increase versus that received in the first cohort," said Mary Spellman, MD, Phio's acting Chief Medical Officer. "PH-762 has been well tolerated in this trial, without relevant immune-related adverse events or other toxicities."

About Phio Pharmaceuticals Corp.

Phio Pharmaceuticals Corp. (Nasdaq: PHIO) is a clinical-stage siRNA biopharmaceutical company advancing its INTASYL^® gene silencing technology focused on immuno-oncology therapeutics. Phio's INTASYL compounds are designed to enhance the body's immune cells to more effectively kill cancer cells. Phio's lead clinical program is an INTASYL compound, PH-762, that silences the PD-1 gene implicated in various forms of skin cancer. The on-going Phase 1b trial (NCT# 06014086) is evaluating PH-762 for the treatment of cutaneous squamous cell carcinoma, melanoma and Merkel cell carcinoma. PH-762 is a potential non-surgical treatment for skin cancers.

For additional information, visit the Company's website, www.phiopharma.com.

 Forward Looking Statements

This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements can be identified by words such as "intends," "believes," "anticipates," "indicates," "plans," "expects," "suggests," "may," "would," "should," "potential," "designed to," "will," "ongoing," "estimate," "forecast," "target," "predict," "could" and similar references, although not all forward-looking statements contain these words. Examples of forward-looking statements contained in this press release include, among others, the possibility that our INTASYL® siRNA gene silencing technology will make the body's immune cells more effective in killing cancer cells, our expectations with respect to the continued safety results of our clinical trial, our expectations with respect to the potential of a viable non-surgical alternative treatment for cutaneous carcinomas, and statements regarding our commercial and clinical strategy, development plans and timelines and other future events.  

These statements are based only on our current beliefs, expectations and assumptions and are subject to inherent uncertainties, risks and changes in circumstances that are difficult to predict and many of which are outside of our control.  Our actual results may differ materially from those indicated in the forward-looking statements as a result of a number of important factors, including, but not limited to, the impact to our business and operations by inflationary pressures, rising interest rates, recession fears, the development of our product candidates, results from our preclinical and clinical activities, our ability to execute on business strategies, our ability to develop our product candidates with collaboration partners, and the success of any such collaborations, the timeline and duration for advancing our product candidates into clinical development, the timing or likelihood of regulatory filings and approvals, the success of our efforts to commercialize our product candidates if approved, our ability to manufacture and supply our product candidates for clinical activities, and for commercial use if approved, the scope of protection we are able to establish and maintain for intellectual property rights covering our technology platform, our ability to obtain future financing, market and other conditions and those identified in our Annual Report on Form 10-K and subsequent Quarterly Reports on Form 10-Q under the caption "Risk Factors" and in other filings the Company periodically makes with the SEC. Readers are urged to review these risk factors and to not act in reliance on any forward-looking statements, as actual results may differ from those contemplated by our forward-looking statements. Phio does not undertake to update forward-looking statements to reflect a change in its views, events or circumstances that occur after the date of this release, except as required by law.  

Contact:
Phio Pharmaceuticals Corp. 
Jennifer Phillips: jphillips@phiopharma.com  
Corporate Affairs  

To view the source version of this press release, please visit https://www.newsfilecorp.com/release/272749

FAQ

What pathologic results did PHIO (PHIO) announce on November 3, 2025 for PH-762?

In the final dose cohort, PH-762 produced 100% clearance in 1 patient, >90% clearance in 1, and >50% clearance in 1, assessed at ~5 weeks.

How many patients have completed treatment in Phio's PH-762 Phase 1b trial (NCT# 06014086)?

A total of 18 patients have completed treatment across five dose-escalation cohorts.

What is the cumulative pathologic response among cSCC patients in PH-762 Phase 1b?

Among 16 cSCC patients: 6 complete responses, 2 near complete responses (>90%), and 2 partial responses (>50%).

Did the Safety Monitoring Committee report any dose-limiting toxicities for PH-762 at the maximum dose?

No; the SMC reported no dose-limiting toxicities or clinically relevant treatment-emergent adverse effects at the maximum dose.

What dose escalation milestone did Phio report for PH-762 in the Phase 1b trial?

The company reported dose escalation to approximately a 20-fold increase versus the first cohort without relevant toxicities.

Does the November 3, 2025 PHIO update indicate clinical progression in treated patients?

No patients in the study have exhibited clinical progression of disease per the announced results.