Phio Submits FDA Briefing Package for PH-762 in Skin Cancer

Phio Pharmaceuticals has submitted a meeting request and comprehensive briefing package to FDA to support the next stage of clinical development for PH-762, its INTASYL short interfereing RNA (siRNA) gene-silencing candidate, in cutaneous squamous cell carcinoma, the company announced September 14, 2026.¹ The submission follows formal completion of the phase 1b trial and describes the nonclinical program, integrated clinical pharmacology data, and the scientific rationale, study design, and pharmacokinetic strategy for a planned phase 2b neoadjuvant study.

"Delivering this comprehensive briefing package to [FDA] is a key achievement for the PH-762 program and an important step toward unlocking its clinical potential in cutaneous squamous cell carcinoma," said Robert J. Bitterman, president and CEO of Phio Pharmaceuticals, in a company press release.¹ "We are encouraged by the phase 1b findings and look forward to working with [FDA] as we pursue the next phase of development."

What did the phase 1b trial show?

In the phase 1b trial (NCT06014086), 22 patients with cutaneous carcinomas completed treatment across 5 dose-escalation cohorts and underwent excision of the treated lesional site. Pathology data showed a 70% overall response rate for squamous cell carcinomas, with complete clearance in 10 of 14 responders, and favorable safety and tolerability across all dose levels.² The trial evaluated PH-762 in patients with cutaneous squamous cell carcinoma, melanoma, and Merkel cell carcinoma.¹

How does PH-762 work?

PH-762 is built on Phio's proprietary INTASYL gene-silencing platform and is designed to silence the programmed cell death protein 1 (PD-1) gene implicated in various forms of skin cancer, intended to enhance the body's immune cells to more effectively kill cancer cells. PH-762 is a potential non-surgical treatment for skin cancers, according to the company.¹

How does gene silencing fit into the broader RNAi therapeutics landscape?

RNA interference (RNAi) is a naturally occurring cellular mechanism that uses small RNA molecules to selectively suppress the expression of disease-causing genes. Over the past decade, the modality has matured from a research concept into a validated therapeutic platform, resulting in multiple approved medicines for genetic, metabolic, and hepatic diseases.³ Despite this progress, delivery beyond the liver remains a significant challenge for many RNAi developers, and companies across the sector continue to invest in new chemistries, targeting approaches, and delivery technologies to expand the modality's reach into additional tissues and disease areas.³

City Therapeutics, for example, raised $99.5 million in a Series B financing round in June 2026 to advance its own next-generation RNAi platform, including a phase 1 candidate targeting Factor XI for thromboembolic disease and a preclinical program for Stargardt disease, an inherited retinal disorder; as with PH-762's intratumoral approach in oncology, such efforts reflect the field's broader push to extend gene silencing beyond its traditional liver-focused applications.⁴

What's next for PH-762?

Phio is preparing to manufacture clinical supplies for the planned phase 2b study, expected to be available in the first quarter of 2027. The dosing phase of the company's nonclinical toxicology study has been completed, and final activities supporting the next phase of clinical development are expected to be finished during the first quarter of 2027.¹

What are the limitations?

FDA submission of a briefing package does not guarantee a favorable regulatory outcome or clearance to proceed with the proposed phase 2b trial design. The phase 1b response-rate data are based on a small, uncontrolled, dose-escalation trial without a placebo or active comparator.

References

1. Phio Pharmaceuticals. Phio announces key development milestone for PH-762 with FDA submission supporting next stage of clinical development in cutaneous squamous cell carcinoma. Press release. Published September 14, 2026. Accessed September 14, 2026. https://phiopharma.com/phio-announces-key-development-milestone-for-ph-762-with-fda-submission-supporting-next-stage-of-clinical-development-in-cutaneous-squamous-cell-carcinoma/
2. Phio Pharmaceuticals. Phio Pharmaceuticals announces key tumor response data from all cohorts in intratumoral PH-762 dose escalation cutaneous carcinoma trial. Press release. Published January 20, 2026. Accessed September 14, 2026. https://phiopharma.com/phio-pharmaceuticals-announces-key-tumor-response-data-from-all-cohorts-in-intratumoral-ph-762-dose-escalation-cutaneous-carcinoma-trial/
3. Setten RL, Rossi JJ, Han SP. The current state and future directions of RNAi-based therapeutics. Nat Rev Drug Discov. 2019;18(6):421-446. doi: 10.1038/s41573-019-0017-4.
4. City Therapeutics. City Therapeutics announces $99.5 million Series B financing to advance next-generation RNAi therapeutics. Press Release. Published June 8, 2026. Accessed September 14, 2026. https://www.citytx.com/news/city-therapeutics-announces-99-5-million-series-b-financing-to-advance-next-generation-rnai-therapeutics