PH-762: A Novel siRNA Immunotherapy Could Transform Skin Cancer Treatment, Says New York Dermatologist

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HEADLINE

PH-762: A Novel siRNA Immunotherapy Could Transform Skin Cancer Treatment, Says New York Dermatologist

SUMMARY

PH-762, an experimental small-interfering RNA (siRNA) therapy designed to silence the PD-1 gene, has shown promising early results in a Phase 1b clinical trial for cutaneous skin cancers. New York Mohs surgeon and dermatologist Dr. Dennis Porto comments on the potential of this non-surgical, gene-targeted approach to reshape skin cancer care.

BACKGROUND: SKIN CANCER AND CURRENT TREATMENTS

Non-melanoma skin cancers such as cutaneous squamous cell carcinoma (cSCC), as well as more aggressive tumors like melanoma and Merkel cell carcinoma, remain major public health concerns. Standard treatments often involve surgical excision or Mohs micrographic surgery, which can lead to scarring, morbidity, repeated procedures, and challenges when tumors are in cosmetically or functionally sensitive areas. Systemic immunotherapy and biologics help in advanced cases but carry risks of immune-related adverse effects and may not be appropriate for all patients.

NEW DEVELOPMENT: WHAT IS PH-762

PH-762 is a self-delivering siRNA therapeutic developed using the INTASYL® platform from Phio Pharmaceuticals. The compound is designed to silence PDCD1 mRNA — the gene encoding PD-1 — within the tumor microenvironment, thereby reducing immune checkpoint inhibition and enabling local T-cell–mediated antitumor response. :contentReference[oaicite:2]{index=2}

An ongoing Phase 1b dose-escalation trial (NCT06014086) is evaluating intratumoral injections of PH-762 in patients with cutaneous squamous cell carcinoma, melanoma, and Merkel cell carcinoma. As of the latest update, 18 patients across multiple dose cohorts have completed four weekly injections and undergone pathological assessment. :contentReference[oaicite:3]{index=3}

In patients with cSCC, cumulative pathology results include several complete responses (100% tumor clearance), near-complete responses (> 90% clearance), and partial responses (> 50% clearance). No dose-limiting toxicities or serious adverse events have been reported to date across the cohorts. :contentReference[oaicite:4]{index=4}

These results suggest PH-762 may offer a safe, well-tolerated, non-surgical alternative for skin cancer — potentially reducing the need for excisions or systemic immunotherapy in select cases.

EXPERT COMMENTARY

“As a Mohs surgeon, I surgically treat skin cancer every day. I am so heartened to see new approaches like siRNA-based therapies that could revolutionize our field. As molecular biology, AI, and RNA technology advances, a new dawn awaits — not just in skin cancer but in all of medicine and beyond,” said Dr. Dennis Porto, MD, MPH, FAAD, clinical assistant professor of dermatology at Mount Sinai, New York City.

CLINICAL SIGNIFICANCE AND OUTLOOK

If ongoing and future trials confirm these early findings, PH-762 could fundamentally change how dermatologists—and surgical oncologists—approach skin cancer. An intratumoral, gene-silencing therapy may reduce or eliminate the need for surgery in certain patients, minimize scarring and morbidity, and offer treatment options for tumors in challenging anatomical locations.

Longer-term follow-up will be required to assess durability of tumor clearance, immune response maintenance, and potential combinations with systemic therapies. The emerging data support deeper investigation of RNA-based immunotherapy in dermatologic oncology.

ABOUT DR. DENNIS PORTO

Dr. Dennis Porto, MD, MPH, FAAD, is a double board-certified Mohs micrographic surgeon and dermatologist practising in New York City. He completed medical school at the University of Iowa, followed by a dermatology research fellowship at Harvard and advanced surgical training. Dr. Porto serves as a clinical assistant professor of dermatology at Mount Sinai and is widely published in dermatologic surgery, oncologic dermatology, and inflammatory skin disease. His practice emphasizes evidence-based, integrative dermatologic care combining medical, surgical, and emerging molecular approaches.