8-K: Phio Pharma Completes Enrollment in PH-762 Skin Cancer Trial

Phio Pharmaceuticals announced the completion of enrollment in its Phase 1b clinical trial for PH-762, an INTASYL siRNA compound targeting PD-1 for skin cancer.

Summary

• Phio Pharmaceuticals has completed enrollment in its Phase 1b clinical trial for PH-762, an INTASYL siRNA lead compound designed to silence the PD-1 gene.
• The trial is evaluating the safety and tolerability of neoadjuvant intratumoral PH-762 in Stages 1, 2, and 4 cutaneous squamous cell carcinoma (cSCC), Stage 4 melanoma, and Stage 4 Merkel cell carcinoma.
• A total of 18 patients with cutaneous carcinomas have completed treatment across five dose-escalating cohorts.
• Pathology results for additional patients in the fifth cohort at the highest dose concentration are expected in Q1 2026.
• Among 16 cSCC patients, 6 achieved a complete response (100% clearance), 2 had a near complete response (>90% clearance), and 2 had a partial response (>50% clearance).
• One patient with metastatic Merkel cell carcinoma showed a partial response (>50% clearance).
• Six cSCC patients and one metastatic melanoma patient had a pathologic non-response (<50% clearance).
• No patients in the study exhibited clinical progression of disease, and PH-762 was well tolerated with no dose-limiting toxicities or clinically relevant treatment-emergent adverse effects.

Sentiment

Score: 7

Explanation: The completion of enrollment in a Phase 1b trial is a positive operational milestone. The initial safety profile is excellent, and the reported efficacy signals, particularly the complete responses in cSCC, are encouraging for an early-stage study. However, it's still a small patient cohort, and further data is needed.

Positives

• Completion of enrollment in the Phase 1b clinical trial for PH-762, marking a significant development milestone.
• PH-762 demonstrated encouraging efficacy signals, with 6 out of 16 cSCC patients achieving a complete response (100% clearance).
• The compound exhibited a favorable safety profile, with no dose-limiting toxicities or clinically relevant treatment-emergent adverse effects reported.
• No patients in the study experienced clinical progression of disease, indicating disease control in the treated population.
• PH-762 was well tolerated across all enrolled patients and escalating dose cohorts.

Negatives

• Six patients with cSCC and one patient with metastatic melanoma experienced a pathologic non-response (<50% clearance) to PH-762 treatment.

Risks

• Actual results may differ materially from forward-looking statements due to factors such as preclinical and clinical activity outcomes, ability to execute business strategies, timing and likelihood of regulatory filings and approvals.
• Risks related to the ability to manufacture and supply product candidates for clinical activities and commercial use if approved.
• Challenges in establishing and maintaining intellectual property rights covering the technology platform.
• The ability to obtain future financing and market conditions may impact operations.
• Other risks identified in the company's Annual Report on Form 10-K and subsequent Quarterly Reports on Form 10-Q under the caption "Risk Factors" and other SEC filings.

Future Outlook

Pathology results for additional patients in the fifth cohort at the highest dose concentration of PH-762 are expected in Q1 2026. The company believes its INTASYL siRNA gene silencing technology has the potential to make the body's immune cells more effective in killing cancer cells, and PH-762 could present a viable non-surgical alternative for skin cancer. The company expects to have sufficient capital to complete the treatment phase of its ongoing Phase 1b clinical trial.

Management Comments

• "Completing enrollment in the Phase 1b trial for PH-762 marks a significant step forward in advancing a promising treatment option for skin cancer." Robert Bitterman, CEO and Chairman of the Board, Phio Pharmaceuticals.
• "We are deeply grateful to the patients, investigators, our partners, and our team for their help in successfully achieving this important milestone." Robert Bitterman, CEO and Chairman of the Board, Phio Pharmaceuticals.

Industry Context

The development of PH-762 aligns with the broader trend in oncology towards targeted therapies and immunotherapies, specifically gene silencing approaches to enhance the immune system's ability to combat cancer. The focus on PD-1 inhibition is a well-established strategy in immuno-oncology, and an intratumoral siRNA approach could offer a novel delivery method and potentially reduce systemic side effects compared to traditional systemic PD-1 inhibitors.

Comparison to Industry Standards

• The complete response rate of 6 out of 16 (37.5%) cSCC patients is notable for a Phase 1b trial, especially given the inclusion of advanced stages (Stages 1, 2, and 4).
• For comparison, standard-of-care systemic PD-1 inhibitors like cemiplimab (Libtayo) or pembrolizumab (Keytruda) have shown objective response rates (ORR) in advanced cSCC typically ranging from 40-50% in pivotal trials, with complete response rates often in the 10-20% range. PH-762's intratumoral delivery might offer a localized advantage.
• The absence of dose-limiting toxicities and clinically relevant treatment-emergent adverse effects is a positive safety signal, which is crucial for early-stage oncology drugs and compares favorably to the known side effect profiles of systemic immunotherapies.

Stakeholder Impact

• Shareholders: Potential positive impact due to the advancement of a key clinical asset and encouraging early-stage results, which could enhance company valuation.
• Patients: Potential benefit from a new, non-surgical treatment option for various skin cancers, especially given the favorable safety profile observed so far.
• Employees: Positive impact on morale and job security due to progress in the company's lead program.
• Investigators/Partners: Continued collaboration and potential for further research and development.

Next Steps

• Continue treating additional patients in the fifth cohort at the highest dose concentration of PH-762.
• Await pathology results for these additional patients, expected in Q1 2026.
• Further clinical development of PH-762 based on trial outcomes.

Key Dates

Recommendation

While the completion of enrollment and initial safety/efficacy data are positive, this is still a Phase 1b trial with a small patient cohort. The results are encouraging but require further validation in larger, later-stage trials. The company's future success hinges on these subsequent trials and regulatory approvals, which carry significant risk. Investors should hold, awaiting more definitive data and progression to later phases before making stronger buy decisions. The non-response rate in some patients also warrants caution.

Keywords

Phio Pharmaceuticals, PHIO, INTASYL, siRNA, PH-762, clinical trial, Phase 1b, skin cancer, cutaneous squamous cell carcinoma, cSCC, melanoma, Merkel cell carcinoma, immuno-oncology, PD-1, gene silencing, biopharmaceutical