First patients receive mRNA therapy for tumour-selective activation
Strand Therapeutics has dosed the first patients in its ASCENT-1 Phase I clinical trial of STX-003, an intravenously delivered self-replicating mRNA therapy designed to selectively express IL-12 within tumours while restricting expression in healthy tissue.
This is the first clinical evaluation of Strand’s SignalLock genetic circuitry, designed to control where therapeutic payloads are expressed in the body.
STX-003 expresses interleukin-12 (IL-12), a potent immune-activating protein with well-documented anti-tumour activity that has historically been limited as a systemic therapy by its narrow therapeutic window.
Strand’s programmable approach is designed to separate where a medicine goes from where it is active. SignalPath delivery technology carries the mRNA to tumour tissue, while SignalLock genetic circuitry reads endogenous microRNA signatures within cells, permitting IL-12 expression in tumour cells while restricting expression in healthy tissue.
If validated clinically, this approach could expand the therapeutic reach of mRNA beyond what can be achieved through delivery alone and enable potent biology that has historically been constrained by systemic toxicity.
“This milestone represents an important step toward what we believe is the next frontier for mRNA medicines as we programme not just what a medicine expresses, but where it is active,” said Jake Becraft, Co-founder and Chief Executive Officer of Strand Therapeutics. “STX-003 brings together the core capabilities of our platform to address the challenge of systemically delivering mRNA beyond the liver while controlling therapeutic activity at the cellular tissue level, a problem the field has been dealing with for years. If successful, this approach could unlock an entirely new class of programmable medicines and therapeutic payloads that have historically been limited by systemic toxicity.”
Validation of the self-replicating mRNA approach
STX-003 builds on Strand’s clinical experience with STX-001, its intratumorally delivered self-replicating mRNA therapy expressing IL-12. In patients with advanced solid tumours who had progressed on prior treatments, STX-001 has demonstrated preliminary evidence of systemic immune activation and anti-tumour activity, including responses in tumours that were never directly injected.
These findings provide early clinical validation of Strand’s self-replicating mRNA approach and the potential for locally expressed IL-12 to drive systemic anti-tumour activity.
ASCENT-1 is a multiple-ascending-dose study evaluating IV STX-003. The Phase I portion is enrolling adults with measurable, locally advanced or metastatic solid tumours for which an anti-PD-1 or anti-PD-L1 therapy is approved and who lack curative options.