Scribe Therapeutics, Inc. (Scribe), a biotechnology company pioneering highly engineered CRISPR technologies designed to reshape the treatment of disease by enabling earlier intervention, improved outcomes, and longer, healthier lives, announced plans to enter the clinic in mid-2026 with STX-1150, its lead product candidate for the treatment of hypercholesterolemia, a major driver of atherosclerotic cardiovascular disease (ASCVD). STX-1150 is a novel liver-targeted therapy designed to epigenetically silence PCSK9 and durably reduce low-density lipoprotein cholesterol (LDL-C) without permanent DNA changes.
The announcement was revealed at the 44th Annual J.P. Morgan Healthcare Conference, underscoring Scribe’s mission to shift cardiovascular care from late, symptom-driven intervention to earlier, durable risk reduction grounded in human genetics.
“Entering the clinic with STX-1150 represents a defining moment for Scribe and the wider genetic medicine field,” said Benjamin Oakes, Ph.D., co-founder and Chief Executive Officer of Scribe Therapeutics. “Scribe has been engineering CRISPR-based medicines with the potency, specificity, and durability profile that can elevate the current standard of care, particularly for large cardiometabolic populations. We designed STX-1150 to overcome many of the limitations of today’s lipid-lowering therapies through powerful epigenetic silencing, and to meaningfully change how cardiovascular risk is managed for millions of patients.”
“Scribe is focused on delivering the cardioprotective effects of naturally occurring genetics as durable CRISPR medicines,” continued Dr. Oakes. “Our preclinical data for the STX-1150 program demonstrate our commitment to advancing nature’s blueprint for better cardiovascular health by developing scalable treatments designed to sustain lipid control and reduce cumulative risk.”
STX-1150: a transformative approach to PCSK9 inhibition for durable, scalable LDL-C lowering
STX-1150, Scribe’s lead cardiometabolic asset, is an epigenetic silencing therapy leveraging the company’s proprietary Epigenetic Long-Term X-Repressor (ELXR) technology and is designed to durably lower LDL-C by repressing expression of PCSK9, a genetically and clinically validated target. Inhibition of PCSK9 is among the most effective known mechanisms to reduce LDL-C.
Unlike CRISPR gene editing, base editing, or prime editing approaches, STX-1150 is designed to achieve long-lasting therapeutic benefit without permanently altering the underlying DNA sequence. By combining durable pharmacology with a non-permanent mechanism, STX-1150 is intended to help address the persistent gap between efficacy observed in controlled settings and real-world outcomes for chronic lipid-lowering therapies, where long-term persistence, repeat dosing, and cumulative polypharmacy burden over years can limit adherence and treatment effectiveness.
In preclinical studies, a single administration of a STX-1150 prototype delivered via lipid nanoparticles has demonstrated >50% LDL-C reduction in non-human primates, with effects sustained for nearly 18 months and ongoing, and was generally well tolerated with no significant liver enzyme elevations compared to control. Scribe believes STX-1150’s designed efficacy and safety profile has the potential to support earlier, longer-lasting LDL-C control and reduce cumulative exposure over time, an important consideration in a disease that progresses over decades.
Scribe plans to initiate the first-in-human Phase 1 study of STX-1150 in mid-2026. The planned study is intended to evaluate safety and tolerability of STX-1150 in individuals with hypercholesterolemia at elevated cardiovascular risk.
New preprint details engineering behind ELXR, Scribe’s proprietary CRISPR epigenetic silencing technology
Scribe also announced the release of a new manuscript describing the engineering behind its ELXR technology that underlies STX-1150. The manuscript reports the strategic design of ELXR molecules incorporating an allosteric regulatory domain to synthetically reconstruct a cell’s native autoinhibitory control to constrain DNA methyltransferase activity, adding a built-in specificity control designed to reduce off-target effects and improve safety while maintaining or enhancing on-target activity.
In the study, allosteric ELXR reduced off-target transcriptome-wide perturbations while maintaining or enhancing on-target repression across genomic loci (average ≥4-fold increased activity), and demonstrated durable target silencing in vivo following lipid nanoparticle delivery with minimal off-target transcriptional effects. Together, the findings introduce an additional regulatory layer designed to improve the fidelity and specificity of CRISPR-based epigenetic silencing for therapeutic applications, differentiating ELXR from the current generation of epigenetic editors used in the field and in the clinic.
Read Also: Worldwide Clinical Trials Enters Definitive Agreement to Acquire Catalyst Clinical Research
