8-K: Phio Pharmaceuticals Advances Skin Cancer Trial to Final Dose Cohort Following Positive Safety Review

Phio Pharmaceuticals Corp. announced that its Safety Monitoring Committee recommended advancing its lead clinical siRNA compound, PH-762, to the fifth and final dose escalation cohort in its Phase 1b skin cancer clinical trial, citing a supportive safety profile.

Summary

• Phio Pharmaceuticals' Safety Monitoring Committee recommended dose escalation to the fifth cohort in the Phase 1b clinical trial (NCT 06014086) for PH-762.
• The trial evaluates the safety and tolerability of intratumoral PH-762 in Stages 1, 2, and 4 cutaneous squamous cell carcinoma (cSCC), Stage 4 melanoma, and Stage 4 Merkel cell carcinoma.
• The fourth cohort, comprising five patients (four cSCC, one Merkel cell carcinoma), showed a supportive safety profile with injections being well-tolerated, no dose-limiting toxicities, serious adverse events, or clinically relevant treatment-emergent adverse reactions.
• Across the first three cohorts, 15 patients with cutaneous carcinomas were treated. Pathological response at Day 36 showed complete tumor clearance in 4 of 9 cSCC patients, near complete response (>90% clearance) in one cSCC patient, and partial response (>50% clearance) in another cSCC patient.
• Three cSCC patients and one metastatic melanoma patient had a pathologic non-response (< 50% clearance), but no patients exhibited clinical progression of disease.

Sentiment

Score: 7

Explanation: The document reports positive clinical trial progression with a favorable safety profile and some promising early efficacy signals (complete responses in a subset of patients). While efficacy data for the latest cohort is pending and some patients had non-responses, the overall tone is positive regarding the advancement of the lead candidate.

Positives

• The Safety Monitoring Committee recommended dose escalation to the fifth cohort for PH-762, indicating a positive safety profile.
• PH-762 demonstrated a supportive safety profile in the fourth cohort, with injections being well-tolerated and no dose-limiting toxicities, serious adverse events, or clinically relevant treatment-emergent adverse reactions reported.
• Across previous cohorts, 4 out of 9 cSCC patients achieved a complete pathological response (100% tumor clearance) at Day 36.
• One cSCC patient had a near complete response (>90% clearance) and another had a partial response (>50% clearance).
• No patients in the trial exhibited clinical progression of disease.

Negatives

• Pathology results related to the efficacy of PH-762 in the fourth cohort are still forthcoming.
• Three cSCC patients and one metastatic melanoma patient in previous cohorts had a pathologic non-response (< 50% clearance).

Risks

• The possibility that INTASYL siRNA gene silencing technology may not make the body's immune cells more effective in killing cancer cells.
• Uncertainties and changes in circumstances that are difficult to predict and outside of control.
• Impact to business and operations from inflationary pressures, rising interest rates, and recession fears.
• Risks related to the development of product candidates and results from preclinical and clinical activities.
• Challenges in executing business strategies and developing product candidates with collaboration partners, and the success of such collaborations.
• Uncertainty regarding the timeline and duration for advancing product candidates into clinical development.
• Uncertainty regarding the timing or likelihood of regulatory filings and approvals.
• Risks related to the success of efforts to commercialize product candidates if approved.
• Challenges in manufacturing and supplying product candidates for clinical activities and commercial use if approved.
• Ability to establish and maintain scope of protection for intellectual property rights covering the technology platform.
• Ability to obtain future financing.
• General market and other conditions.

Future Outlook

Phio Pharmaceuticals anticipates that intratumoral administration of the highest dose concentration of PH-762 in cohort 5 will result in a similar favorable safety profile. The company expects to complete enrollment in the final cohort of this trial in the third quarter of 2025.

Management Comments

• "We are encouraged by the continuing safety profile of PH-762 having now progressed through four escalating dose concentrations, and we anticipate that IT administration of the highest dose concentration of PH-762 in cohort 5 will result in a similar safety profile." Mary Spellman, MD, acting Chief Medical Officer.
• "The continuing favorable safety profile of PH-762 through the fourth cohort provides promise of a well-tolerated treatment for skin cancer." Robert Bitterman, CEO and Chairman.

Industry Context

This announcement highlights progress in the immuno-oncology space, specifically targeting skin cancers with siRNA gene silencing technology. The development of non-surgical treatments for skin cancers represents a significant area of unmet medical need and innovation within the biopharmaceutical industry, where companies are increasingly exploring novel modalities beyond traditional chemotherapy and radiation.

Comparison to Industry Standards

• No specific comparable companies, projects, or results were mentioned in the document to allow for a direct comparison to industry standards. The document focuses solely on the internal progress of Phio's PH-762 trial.

Stakeholder Impact

• Shareholders: Positive clinical trial progress could increase investor confidence and potentially lead to share price appreciation, though risks remain.
• Patients: Potential for a new, well-tolerated, non-surgical treatment option for various skin cancers, including cSCC, melanoma, and Merkel cell carcinoma.
• Employees: Continued progress in the clinical pipeline supports job security and potential for future growth.

Next Steps

• Complete enrollment in the fifth (expected final) cohort of the Phase 1b clinical trial for PH-762.
• Pathology results related to the efficacy of PH-762 in the fourth cohort will be forthcoming.

Key Dates

Recommendation

Keywords

Phio Pharmaceuticals, PHIO, siRNA, INTASYL, gene silencing, immuno-oncology, skin cancer, cutaneous squamous cell carcinoma, cSCC, melanoma, Merkel cell carcinoma, clinical trial, Phase 1b, dose escalation, safety profile, oncology, biopharmaceutical, NCT 06014086