Researchers at an Australian university are advancing a novel RNA-based therapy that directly targets insulin resistance, the underlying driver of type 2 diabetes, bringing the approach closer to human testing and potentially offering a fundamental shift in how the disease is treated.
The project, led by Professor Rakesh Veedu at Murdoch University’s Personalised Medicine Centre in Perth, Western Australia, centers on a proprietary RNA molecule called PGP-011. Developed through Murdoch spinout ProGenis Pharmaceuticals, the compound uses a next-generation chemistry known as thiomorpholinos (TMOs), co-invented with Professor Marvin Caruthers of the University of Colorado.
Unlike existing type 2 diabetes drugs, such as metformin, SGLT2 inhibitors, GLP-1 receptor agonists and insulin, that primarily manage elevated blood glucose by enhancing insulin secretion, improving sensitivity in a limited way or slowing glucose absorption, PGP-011 aims to restore normal insulin signaling at the cellular level. Preclinical data suggest the approach could reverse insulin resistance in key tissues, including muscle and liver, where the defect is most pronounced.
Insulin resistance, in which cells fail to respond adequately to insulin, is widely regarded as the primary pathophysiological feature of type 2 diabetes. It precedes hyperglycemia by years and persists even as beta-cell function declines. Current therapies rarely address this root mechanism head-on, leaving many patients requiring escalating doses or multiple agents over time. A treatment that safely and durably corrects insulin resistance could reduce or eliminate the need for those interventions, potentially lowering complication rates and healthcare costs.
Professor Veedu, a chemical biologist and ProGenis co-founder, described the molecule’s design as a deliberate effort to overcome limitations of earlier RNA therapeutics. “Our goal is to develop a therapy that’s not only more effective in addressing insulin resistance, but also safer and easier to use,” he said in a university release dated December 11, 2025.
Thiomorpholinos represent an evolution of morpholino oligonucleotides, which are synthetic nucleic acid analogs resistant to enzymatic degradation and capable of modulating gene expression without triggering strong immune responses. ProGenis has optimized the chemistry for improved tissue delivery, stability and potency, allowing subcutaneous or potentially oral administration, a major advantage over many RNA drugs that require intravenous delivery or specialized carriers.
While full preclinical results remain unpublished in peer-reviewed journals, university statements indicate encouraging outcomes in rodent models of diet-induced and genetic insulin resistance. Treated animals reportedly showed normalized glucose uptake, reduced hepatic glucose output and improved whole-body insulin sensitivity without hypoglycemia or significant off-target effects.
The team now plans non-human primate studies in 2026 to confirm safety, pharmacokinetics and efficacy in a species more closely resembling human physiology. If those data support progression, first-in-human trials could begin in late 2026, likely as a Phase 1 study focused on safety, tolerability and preliminary pharmacodynamic markers in healthy volunteers and patients with type 2 diabetes.
ProGenis, launched with support from Murdoch University and the Perron Institute, operates within the Personalised Medicine Centre, a collaborative hub that integrates laboratory innovation with clinical translation. The center’s emphasis on tailored therapies aligns with broader trends in precision medicine, though the diabetes program stands out for its focus on a high-prevalence chronic condition affecting more than 500 million adults worldwide.
Type 2 diabetes imposes a massive global burden, driving cardiovascular disease, kidney failure, neuropathy and vision loss. In Australia alone, nearly 1.3 million people live with the diagnosis, with annual direct healthcare costs exceeding A$2 billion. Prevalence continues to climb in parallel with obesity and aging populations, underscoring the need for disease-modifying treatments beyond symptom control.
The RNA approach joins a crowded but diverse pipeline of potential insulin-sensitizing agents. Other candidates include small molecules targeting mitochondrial function, inflammation pathways or adipokine signaling, as well as gene-editing and cell-based therapies. Recent high-profile advances, such as stem-cell-derived islet transplants that reversed severe type 1 diabetes in small cohorts have heightened expectations across the diabetes field, though type 2 therapies face different hurdles given the disease’s multifactorial nature.
Experts caution that translating preclinical success to humans remains challenging. RNA therapeutics have achieved landmark approvals in rare genetic disorders (e.g., patisiran for hereditary transthyretin amyloidosis, inclisiran for hypercholesterolemia), but scaling efficacy and safety to common metabolic diseases has proven difficult. Delivery to metabolically active tissues, duration of effect and long-term immunogenicity are key concerns.
Even so, the prospect of a first-in-class therapy that tackles insulin resistance directly has drawn attention from investors and clinicians. ProGenis has secured early-stage funding to support the primate work and IND-enabling studies, though specific figures were not disclosed.
Professor Veedu emphasized the collaborative nature of the effort. “This is the result of years of chemistry innovation combined with deep understanding of diabetes pathophysiology,” he noted. The involvement of Caruthers, a pioneer in nucleic acid synthesis whose foundational work enabled many modern oligonucleotide drugs, lends credibility to the technical platform.
For patients and physicians, the timeline remains tentative. Late 2026 marks the earliest plausible start for human dosing, with efficacy readouts likely years away even under an optimistic scenario. Phase 2 and Phase 3 programs would then be required to demonstrate meaningful improvements in glycemic control, weight, cardiovascular risk factors and quality of life, endpoints regulators demand for approval.
If successful, PGP-011 or a successor could redefine type 2 diabetes care, moving the field from chronic management toward disease modification or even remission in a subset of patients. For now, the Murdoch team’s advance represents one of the more intriguing RNA-based bets in metabolic disease, watched closely as it navigates the long path from laboratory to clinic.
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