Sironax’s SARM1 allosteric inhibitor gains FDA Fast Track status for chemotherapy-induced peripheral neuropathy

Edited by Robert McTiernan··4 min read

There are no approved treatments for chemotherapy-induced peripheral neuropathy (CIPN), a condition affecting a substantial proportion of cancer patients receiving neurotoxic regimens — a gap that has drawn increasing attention from drug developers targeting the underlying biology of axonal degeneration.

Sironax, a clinical-stage biotechnology company headquartered in Massachusetts while basing R&D in China, announced that the US FDA has granted Fast Track Designation to SIR2501, a first-in-class allosteric inhibitor of sterile alpha and TIR motif-containing protein 1 (SARM1), for the treatment of CIPN. The designation reflects the absence of approved therapies in this setting and enables more frequent FDA interactions, rolling review of a future NDA or BLA submission, and potential eligibility for Priority Review.

SIR2501 works by binding SARM1 at a site distinct from its catalytic domain, maintaining the enzyme in an inactive state. SARM1 functions as a central executioner of Wallerian degeneration — the programmed self-destruction of axons following injury or metabolic stress — and its activation drives the nicotinamide adenine dinucleotide (NAD+) depletion cascade that underlies nerve fiber loss. By blocking this pathway allosterically rather than at the active site, Sironax contends that SIR2501 avoids potential off-target effects associated with orthosteric inhibition, though that distinction has not yet been evaluated in controlled clinical comparisons.

The company reports that SIR2501 demonstrated neuroprotective effects across multiple preclinical models, though it has not cited a peer-reviewed publication, conference abstract, or dataset identifier to substantiate that claim in the current announcement.

The program has advanced into human testing. A Phase I randomized, double-blind, placebo-controlled single and multiple ascending dose study in healthy adults — conducted in Australia with a bridging cohort in China — was completed, with Sironax reporting in July 2025 that results aligned with preclinical expectations. A Neuroscience 2025 conference abstract presented in November 2025 indicated that SARM1 inhibition was measurable in the human central nervous system across ascending doses, though precise numeric values — including percentage inhibition, cyclic ADP-ribose suppression, or CNS exposure metrics — were not publicly disclosed in the abstract summary. Full quantitative data are expected to be presented at ASCO 2026, where an abstract titled “SARM1 Inhibition to Prevent Chemotherapy-Induced Peripheral Neuropathy: Translational and Early Clinical Evaluation of SIR2501” (Abstract 12148) is scheduled for May 30, 2026.

A global Phase I/II study, sponsored by Sironax Ltd and enrolling patients with ALS and patients receiving paclitaxel chemotherapy to evaluate CIPN prevention, is currently recruiting in Australia and China under protocol SIR2501-GLB-201. No efficacy or safety data from this patient-facing study have been publicly disclosed.

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Research context

CIPN develops in a large proportion of patients treated with neurotoxic agents including taxanes, platinum compounds, and vinca alkaloids. Symptoms — which include burning or shooting pain, loss of temperature and tactile sensation, muscle weakness, and impaired fine motor function — can be severe enough to prompt dose reductions or discontinuation of otherwise active cancer regimens, with downstream effects on treatment outcomes. Despite the clinical burden, no drug has received US FDA approval specifically for CIPN prevention or treatment, and current management relies on symptomatic approaches with limited evidence.

The SARM1 pathway has attracted interest as a mechanistic target because it sits upstream of the axonal degeneration cascade common to multiple peripheral and central neuropathies. Preclinical genetic and pharmacological studies have shown that SARM1 loss-of-function or inhibition delays Wallerian degeneration in rodent models of chemotherapy-induced and traumatic nerve injury, providing the translational rationale for clinical development. However, no SARM1 inhibitor has yet demonstrated efficacy in a randomized clinical trial.

Sironax is not the only company pursuing this biology. Disarm Therapeutics, acquired by Eli Lilly (NYSE: LLY) in 2020, had advanced SARM1 inhibitor research, though Lilly has not disclosed a clinical-stage SARM1 program in CIPN as of the date of this report. The competitive field remains early, and SIR2501 appears to be among the first SARM1-directed molecules to reach patient-focused clinical evaluation.

Sironax’s broader pipeline includes SIR4156, a NAMPT activator, and SIR9900, a RIPK1 inhibitor, alongside ongoing preclinical research. The company was named to the 2025 Endpoints 11 list. It has not disclosed a stock ticker, indicating it remains privately held.

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