Phio Pharmaceuticals (NASDAQ:PHIO) is advancing its lead immuno-oncology candidate, PH-762, as a potential neoadjuvant treatment for cutaneous squamous cell carcinoma, President and Chief Executive Officer Robert Bitterman said during a Virtual Investor Conferences presentation.
The company’s approach centers on INTASYL, a self-delivering short interfering RNA platform designed to silence specific genes. PH-762 targets PD-1, a protein that can inhibit immune-cell activity. By temporarily reducing PD-1 production within the tumor, Phio aims to reactivate T cells and improve their ability to attack cancer cells, Bitterman said.
Focus on Cutaneous Squamous Cell Carcinoma
According to Bitterman, surgical treatment can be complicated by a lesion’s size and location, as well as patient health factors including diabetes, immunosuppression and use of blood-thinning medications. He said a neoadjuvant therapy that reduces tumors before surgery could potentially help minimize recovery time, disfigurement, reconstructive procedures and surgical frequency.
The company is initially focused on high-risk lesions, including those larger than 2 centimeters and those located on areas such as the head, neck, hands, feet and lower leg. Bitterman estimated there are about 1.1 million annual incidences of such high-risk lesions among 1.8 million total annual incidences of cutaneous squamous cell carcinoma. He placed the potential neoadjuvant addressable market at approximately $2 billion to $3 billion.
Bitterman said Phio’s objective is to complement dermatologic surgery rather than replace it. He said physicians have expressed interest in a treatment that could make surgical procedures less difficult while preserving the role of surgery in patient care.
Phase 1b Results and Next Study
PH-762 has completed a Phase 1b study involving 22 patients, according to Bitterman. The study evaluated four injections administered over three weeks across five escalating dose cohorts.
In the highest-dose cohort, six of seven patients responded, representing an 85% response rate, Bitterman said. Four of the six responders had 100% pathologic clearance of cancer in the tissue, while one had greater than 90% clearance and another had greater than 50% clearance. Across all cohorts, the overall response rate was 65%, he said.
The company did not identify immune-related or dose-limiting toxicities as doses increased 20-fold during the trial, according to Bitterman. He characterized the combination of efficacy and safety findings as the principal takeaway from the early-stage study.
“If you do not have safety that goes along with that, it is problematic,” Bitterman said. “In our case, we are very fortunate in the way that the study turned out that we could not find a toxic dose, even though we increased it 20-fold.”
Phio is preparing a Phase 2b study for PH-762 and expects the trial to begin in the first quarter of the following year, Bitterman said. The company is completing the clinical design and responding to FDA questions related to a briefing package it submitted. He added that the Phase 1b data, which included patients with tumors in seven body locations and lesions ranging from about 1 centimeter to 2.9 centimeters, helped inform the next trial’s design.
Manufacturing, Intellectual Property and Pipeline
Bitterman said Phio recently completed commercial-scale production of PH-762’s active pharmaceutical ingredient following a 16-month process. The material is being shipped to the company’s drug-product manufacturer for production of clinical supplies intended to support the planned Phase 2b trial.
The company also completed the treatment phase of a longer-term nonclinical toxicology study, which Bitterman said could support future clinical studies extending beyond four weeks.
Phio said its intellectual-property portfolio includes 54 issued patents extending to 2044. Bitterman said the patents cover the company’s core technology, gene-targeting sequences, compounds, methods of use and potential combinations with monoclonal antibodies.
Beyond PH-762, Phio is developing a pre-IND candidate that targets BRD4, a gene associated with multiple cancers. The company plans to move that program forward after PH-762 enters the Phase 2b clinic. Bitterman also said Phio may seek strategic partners for additional gene-silencing programs that address solid tumors, hematologic cancers and infectious diseases.
Financial Position
Phio reported a cash runway into the second half of 2027, along with $6.3 million of at-the-market capacity. Bitterman said the company has no debt, approximately 12 million common shares outstanding and about 13 million fixed-price warrants exercisable at $2.05.
He said Phio operates with seven full-time employees and contracted subject-matter experts, using a lean structure intended to direct funding primarily toward development programs and the company’s patent portfolio.
About Phio Pharmaceuticals (NASDAQ:PHIO)
Phio Pharmaceuticals Corp. is a clinical-stage biotechnology company focused on developing immuno-oncology treatments based on its INTASYL self-delivering RNAi technology. The platform is designed to enable small interfering RNA (siRNA) molecules to enter cells without the use of conventional delivery vehicles and to reduce the expression of selected genes involved in cancer biology and immune-system activity.
The company’s pipeline has included product candidates intended to improve the ability of immune cells to recognize and destroy tumors.
