8-K: Phio Pharmaceuticals Secures US Manufacturing for PH-762 and Reports Positive Phase 1b Clinical Trial Results

Phio Pharmaceuticals announced a new U.S. manufacturing agreement for its lead compound PH-762 and reported promising pathology results from its Phase 1b clinical trial, including complete and partial tumor responses in skin cancer patients.

Summary

• Phio Pharmaceuticals Corp. has entered into a comprehensive drug substance development services agreement with a U.S. manufacturer for its lead compound, PH-762.
• The agreement covers analytical and process development and cGMP manufacture of PH-762, a critical step for advancing its intratumoral program for cutaneous carcinomas.
• Pathology results are available for four of five patients in the fourth cohort of the ongoing Phase 1b dose escalation clinical trial (NCT 06014086) for PH-762.
• One patient with cutaneous squamous cell carcinoma (cSCC) achieved a complete pathologic response (100% tumor clearance).
• One patient with Stage 4 metastatic Merkel cell carcinoma showed a partial response (> 50% clearance).
• Two cSCC patients had a pathologic non-response (<50% tumor clearance), and results for one cSCC patient are pending.
• Across all four cohorts, 15 patients with cutaneous carcinomas have been treated.
• Cumulative results for 13 cSCC patients include five complete responses (100% clearance), one near complete response (>90% clearance), one partial response (>50% clearance), and six pathologic non-responses (<50% clearance).
• The single Merkel cell carcinoma patient with Stage 4 metastatic disease had a partial response (>50% clearance).
• The single melanoma patient was a non-responder (<50% clearance).
• PH-762 has been well tolerated, with no dose-limiting toxicities, clinically relevant treatment-emergent adverse effects, or clinical progression of disease observed in any enrolled patients.
• Phio is currently enrolling patients for the 5th and expected final cohort in the Phase 1b study.

Sentiment

Score: 8

Explanation: The filing presents strong positive clinical trial results for a subset of patients, particularly a complete response in cSCC and a partial response in metastatic Merkel cell carcinoma, coupled with a favorable safety profile. The strategic manufacturing agreement further de-risks future development. While there were non-responders, the overall tone and specific positive outcomes are significant for an early-stage biopharmaceutical company.

Positives

• Secured a comprehensive drug substance development services agreement with a U.S. manufacturer for PH-762, ensuring a domestic supply chain.
• One patient with cutaneous squamous cell carcinoma (cSCC) achieved a complete pathologic response (100% tumor clearance) in the Phase 1b trial.
• One patient with Stage 4 metastatic Merkel cell carcinoma showed a partial response (> 50% clearance) in the Phase 1b trial.
• PH-762 demonstrated a positive safety profile with no dose-limiting toxicities or clinically relevant treatment-emergent adverse effects reported across all dose escalation cohorts.
• No patients exhibited clinical progression of disease during the trial.
• Cumulative results for 13 cSCC patients show 5 complete responses (100% clearance), 1 near complete response (>90% clearance), and 1 partial response (>50% clearance).
• The company is advancing to the 5th and expected final cohort of the Phase 1b study, indicating progress towards further clinical development.

Negatives

• Two patients with cutaneous squamous cell carcinoma (cSCC) in the fourth cohort were reported as having a pathologic non-response (<50% tumor clearance).
• The single melanoma patient in the trial was a non-responder (<50% clearance).
• Six out of 13 cSCC patients cumulatively showed a pathologic non-response (<50% clearance).

Risks

• Impact to business and operations by inflationary pressures, rising interest rates, and recession fears.
• Uncertainty regarding the development of product candidates.
• Potential for actual results to differ materially from preclinical and clinical activities.
• Ability to execute on business strategies.
• Ability to develop product candidates with collaboration partners and the success of such collaborations.
• Timeline and duration for advancing product candidates into clinical development.
• Timing or likelihood of regulatory filings and approvals.
• Success of efforts to commercialize product candidates if approved.
• Ability to manufacture and supply product candidates for clinical activities and commercial use if approved.
• 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 its INTASYL siRNA gene silencing technology will enhance the body's immune cells to more effectively kill cancer cells. The company is progressing its lead clinical program, PH-762, through its Phase 1b trial, with the expectation of completing the final cohort soon. Management believes PH-762 may present a viable non-surgical alternative in the expanding skin cancer market.

Management Comments

• "We are delighted to be partnering with an organization known for its quality and expertise in oligonucleotide chemistry sequencing. Additionally, we value the strategic advantages to our management team of working with a U.S. based organization." Robert J. Bitterman, President & CEO.
• "The positive safety and efficacy outcomes through the fourth cohort continue to indicate that PH-762 may present a viable non-surgical alternative in this large and continually expanding skin cancer market." Robert Bitterman, CEO and Chairman.

Industry Context

The agreement with a U.S. manufacturer for drug substance development and cGMP manufacturing aligns with a broader industry trend towards securing domestic supply chains and ensuring quality control for advanced therapeutics, particularly in the biopharmaceutical sector. The positive early-stage clinical trial results for PH-762 in skin cancers position Phio Pharmaceuticals within the competitive immuno-oncology landscape, where novel non-surgical treatments for common cancers like cSCC and aggressive ones like Merkel cell carcinoma are highly sought after. The focus on PD-1 gene silencing through siRNA technology represents an innovative approach within the immuno-oncology field, aiming to enhance the body's natural immune response against cancer.

Comparison to Industry Standards

• The complete pathologic response (100% tumor clearance) in one cSCC patient and partial response (>50% clearance) in a Stage 4 metastatic Merkel cell patient are promising for a Phase 1b dose escalation study, especially given the challenging nature of these cancers. While direct comparisons to specific competitor drugs at this early stage are difficult without more detailed efficacy data, these results suggest PH-762's potential as a non-surgical alternative.
• The safety profile, with no dose-limiting toxicities or clinically relevant treatment-emergent adverse effects, is a strong positive, indicating good tolerability, which is crucial for advancing to later-stage trials and for potential combination therapies. This compares favorably to many oncology treatments that often come with significant side effects.
• The cumulative response rates for cSCC (5 complete, 1 near complete, 1 partial out of 13 patients) indicate a meaningful proportion of responders, which is encouraging for an early-stage trial targeting a broad patient population with varying stages of disease.

Stakeholder Impact

• Shareholders: Positive clinical trial results and a strategic manufacturing agreement could increase investor confidence and potentially lead to share price appreciation.
• Patients: The development of PH-762 offers a potential non-surgical treatment option for various skin cancers, including cSCC, melanoma, and Merkel cell carcinoma, which could improve patient outcomes and quality of life.
• Employees: Securing a manufacturing partner and advancing clinical trials indicates continued progress and stability for the company, potentially benefiting employees.
• Suppliers/Partners: The new U.S. manufacturing agreement creates a significant partnership opportunity for the selected manufacturer.

Next Steps

• Enrollment of patients for the 5th and expected final cohort in the Phase 1b dose escalation study for PH-762.
• Continued analytical and process development and cGMP manufacture of PH-762 under the new U.S. manufacturing agreement.
• Further clinical development of PH-762 as a potential non-surgical treatment for skin cancers.

Key Dates

Recommendation

The filing indicates significant positive progress for Phio Pharmaceuticals. The Phase 1b clinical trial results for PH-762, particularly the complete response in cSCC and partial response in metastatic Merkel cell carcinoma, are highly encouraging for an early-stage asset, especially given the excellent safety and tolerability profile. These results suggest strong potential for PH-762 as a non-surgical treatment in a large and growing market. Furthermore, securing a U.S. manufacturing agreement for the lead compound is a crucial de-risking step, ensuring future supply and quality control. While some patients were non-responders, the overall data presented is compelling for a clinical-stage biopharmaceutical company, indicating a strong investment opportunity with significant upside potential if these positive trends continue in later stages.

Keywords

Phio Pharmaceuticals, PHIO, siRNA, INTASYL, gene silencing, immuno-oncology, cancer therapeutics, PH-762, PD-1, cutaneous squamous cell carcinoma, melanoma, Merkel cell carcinoma, Phase 1b clinical trial, drug substance manufacturing, biopharmaceutical, clinical-stage, oncology, skin cancer, non-surgical treatment