Strand Therapeutics announced preliminary Phase 1 clinical data for its lead investigational candidate STX-001, marking the first clinical evidence of the company's proprietary programmable mRNA technology platform. The ongoing first-in-human Phase 1, open-label, dose-escalation clinical trial demonstrated a favorable safety profile and encouraging signs of anti-tumor activity as a monotherapy in patients with immune checkpoint inhibitor-refractory solid tumors, including melanoma and other solid tumor indications.
As of the April 3, 2025 data cutoff, the trial had enrolled 22 patients across multiple sites in the United States and Australia. All patients were treated with STX-001 as a monotherapy with injections to surface accessible lesions. The data will be presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago on June 1 by Sarina Piha-Paul, M.D., professor of Investigational Cancer Therapeutics at The University of Texas MD Anderson Cancer Center.
Clinical Activity and Safety Profile
The Phase 1 trial demonstrated multiple RECIST responses, including a confirmed complete response and multiple partial responses. Additionally, there were multiple cases of prolonged disease stabilization. STX-001 was well-tolerated up to 300 µg, with treatment-related adverse events consistent with the therapy's intended mechanism of action of immune activation.
"This investigational therapy has the potential to address an important unmet need in patients with checkpoint inhibitor-refractory advanced cancers," said Dr. Piha-Paul. "We're observing systemic immune activation and antitumor responses, including in non-injected lesions, across multiple tumor types, which is encouraging and supports continued evaluation."
Pharmacodynamic Activity
Biomarker analysis confirmed dose-dependent increases in plasma IL-12 and IFN-γ, as well as infiltration of immune cells within the tumor microenvironment. These findings support the mechanism of action of STX-001, which encodes IL-12, an immunomodulatory protein designed to reprogram the tumor microenvironment and stimulate a systemic anti-tumor immune response.
"This is a transformative moment for Strand and for the field of synthetic mRNA therapeutics," said Jake Becraft, PhD, CEO and Co-founder of Strand Therapeutics. "The Phase 1 data for STX-001 provide early clinical validation of our platform's ability to deliver programmable, tumor-localized immunotherapy safely and effectively."
Technology Platform and Mechanism
Unlike traditional mRNA therapies, Strand's approach uses self-replicating mRNA, ensuring localized and durable therapeutic activity. STX-001 is an investigational multi-mechanistic, synthetic self-replicating mRNA technology that expresses an IL-12 cytokine for an extended period of time, directly injected into the tumor microenvironment to promote immune modulation and antitumor activity.
Professor Georgina Long, Medical Director of Melanoma Institute Australia and Chair of Melanoma Medical Oncology and Translational Research at MIA and Royal North Shore Hospital, The University of Sydney, commented: "I am encouraged by this early data. While intratumoral therapies offer a promising approach by initiating immune activation at the injected tumor site, they have historically struggled to generate robust systemic responses. STX-001 may represent a meaningful step forward, with early clinical evidence showing cases of regression of non-injected lesions, a sign of systemic immune engagement."
Development Timeline and Future Plans
The company is currently conducting dose expansion in the Phase 1 trial. Upon completion, Strand plans to transition into a Phase 2 trial of STX-001 as a monotherapy. The company also plans to initiate dose escalation of STX-001 in combination with checkpoint inhibitors and expand into additional solid tumor indications.
Strand is advancing a broader pipeline powered by the company's first-in-class cell-type specific mRNA engineering platform, including advancing STX-003, an intravenously administered version of STX-001, to patients in 2026.
Addressing Unmet Medical Need
Tasuku Kitada, PhD, Co-Founder, President, and Head of R&D at Strand Therapeutics, emphasized the clinical significance: "Patients who are refractory to immune checkpoint inhibitors urgently need new treatment options. While IL-12 has long been recognized as a powerful immune stimulator, its clinical potential has been limited by toxicity, and to date, no IL-12–based therapies have been approved by the FDA. STX-001 is designed to overcome these challenges, delivering localized IL-12 expression to activate the tumor microenvironment and drive systemic immune responses, all while seeking to minimize toxicities."
The company received IND clearance from the U.S. Food and Drug Administration (FDA) in December 2023 to initiate a Phase 1/2 clinical trial for STX-001, and announced its first patient dosed just before the 2024 ASCO Annual Meeting. The study details can be found at clinicaltrials.gov using identifier NCT06249048.
