Sironax Ltd.

“We\'re looking at all the options of how to get drugs across the blood-brain barrier,” Novartis\' global development head of neurology and gene therapy Nazem Atassi, M.D., told Fierce.\n Novartis may be launching an array of vehicles to shuttle drugs across the blood-brain barrier, but executives told Fierce that the Swiss pharma is “always looking” for new ways to traverse this final frontier of neuroscience.The company\'s most recent play was a $165 million upfront deal with SciNeuro Pharmaceuticals in January for the worldwide license to an amyloid beta-targeting antibody for Alzheimer\'s disease. One of the appeals of SciNeuro\'s monoclonal antibody is how it harnesses transferrin receptor (TFR) to drive drugs into the brain, according to Nazem Atassi, M.D., global development head of neurology and gene therapy at Novartis.“TFR is the most advanced [modality] in the space to get drugs through the blood-brain barrier,” Atassi told Fierce in an interview last week.Finding ways to bypass this barrier has been a key goal for neurodegenerative-minded companies for years. The barrier protects the inner surfaces of the blood vessels inside the brain and controls how certain chemical molecules go into and out of the brain.Novartis’ fellow Swiss pharma Roche, which has a brain shuttle bispecific 2+1 amyloid-beta-targeting monoclonal antibody in phase 3 development, penned a shuttle-focused deal with Manifold Bio late last year to work on direct-to-vivo AI-guided brain shuttles.By that point, Novartis had already placed one neuroscience bet on TFR when it handed $200 million to Arrowhead Pharmaceuticals to develop its preclinical siRNA program targeting alpha-synuclein in order to treat Parkinson’s and other synucleinopathies.“TFR is very widely expressed, although very highly expressed on the brain endothelium,” Bob Baloh, M.D., Ph.D., global head of neuroscience at Novartis Biomedical Research, told Fierce in the same interview.“You can tune TFR, and we\'re seeing those molecules get into the clinic across a variety of companies—including ours,” he said.The collaborations with Arrowhead and SciNeuro involve attempting to tune TFR to get drugs into the brain and remain in preclinical testing for now. But Novartis’ work to tune TFR to muscle is further ahead thanks to the pharma’s $12 billion buyout of Avidity Biosciences in October 2025.That deal gave Novartis ownership of Avidity’s pipeline of clinical-stage antibody-oligonucleotide conjugates for muscle dystrophies. They include the Duchenne muscular dystrophy therapy delpacibart zotadirsen (del-zota), which uses an anti-TFR1 antibody to deliver an oligonucleotide to target cells. The therapy was tied to a statistically significant 25% increase in dystrophin production among people amenable to exon 44 skipping and is currently on track to be submitted to regulators in the coming weeks. Meanwhile, a phase 3 study for delpacibart etedesiran in myotonic dystrophy Type 1 is due to read out in the second half of the year, with a late-stage study of the DUX4-targetting delpacibart braxlosiran for facioscapulohumeral muscular dystrophy currently enrolling, Atassi explained.“If you look across the three programs in clinic that Avidity has, you will see common themes—they\'re all muscle diseases, they all use TFR [to] drive the payload to the muscle, and in all of them you see very robust target engagement,” he said.Not content with riding Avidity’s pipeline of muscle dystrophy drugs to regulators, Novartis is also hoping to turn the company’s tech to neurodegenerative diseases like Alzheimer’s and Parkinson’s.It’s a “little bit easier” to tune TFR to muscle because correctly-tuned formats can enter these tissues quite effectively, according to Baloh. “It\'s a little bit harder to tune for the brain, and that\'s why I think if you look across the industry, you\'ll see that the brain programs are just a little behind,” he added.Whether trying to tackle Alzheimer’s by targeting amyloid beta, tau or neuroinflammation, all companies run headfirst into the blood-brain barrier.That\'s why Novartis has another iron in the fire thanks to a deal last year to give Sironax $175 million in upfront and near-term payments in return for the option to license the Massachusetts-based biotech’s blood-brain barrier crossing tech. For now, the pharma is keeping the specific targets of that pact under wraps.Baloh sees the recent progress made across the space as “exciting” because it means getting drugs to the brain has become “an engineering problem” rather than remaining a pipe dream.“That\'s where we obviously see a lot of opportunities, so we\'re doing a whole series of deals now,” he told Fierce.Despite having bet on a range of options, the Novartis execs aren’t ruling out splashing more cash in the future.“We believe there could be other shuttle systems, and simultaneously we\'re going to investigate if those do perform better or differently from what you can do with TFR, because we really believe that the opportunity space is so large that that\'s the right way to approach it,” Baloh said.“We have really strong teams internally working on the blood-brain barrier—they\'re collaborating actually with externals and academics,” he continued. “I don\'t think you will really ever only have one solution to this problem,” Baloh said. “Having a toolbox that you can then use is probably the best way to approach.” “We\'re absolutely always looking,” Baloh added when asked whether Novartis is eying up other blood-brain barrier plays.Atassi agreed that no good solutions are off the table: “Beyond TFR, we\'re looking at all the options of how to get drugs across the blood-brain barrier.”

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. 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. This article was generated with AI assistance and reviewed and edited by the AllSci editorial team Explore more at AllSci News: https://allsci.com/news/ Leave a Reply Cancel reply Your email address will not be published. Required fields are marked * Comment * Name * Email * Website Privacy Terms About Us Copyright © 2026. AllSci Corp. All rights reserved.

CIPN is a common nerve-damaging side effect of chemotherapy with no FDA-approved treatment options Fast Track designation reflects the significant unmet need and enables potential accelerated drug development WALTHAM, Mass., May 11, 2026 (GLOBE NEWSWIRE) -- Sironax, a global clinical-stage biotechnology company developing transformative therapies for neurodegenerative, inflammatory and immunologic, metabolic, and rare diseases, today announced that the U.S. Food and Drug Administration (FDA) has designated its SARM1 inhibitor SIR2501 as a Fast Track product for chemotherapy-induced peripheral neuropathy (CIPN). SIR2501 is a first-in-class allosteric inhibitor of SARM1, a key driver of nerve damage in a broad range of neurological diseases. The FDA grants Fast Track designation to facilitate the development and expedite the review of drugs to treat serious conditions, fill unmet medical needs, and bring promising therapies to patients more quickly. Drugs granted this designation are eligible for more frequent interactions with the agency regarding development plans, a rolling NDA/BLA review, and potential priority review and accelerated approval. “Fast Track designation for SIR2501 in CIPN is a meaningful recognition of the urgent unmet medical need and the potential of our entire SARM1 program,” said Dr. Shefali Agarwal, Sironax President and CEO. “The FDA’s designation not only validates our approach in CIPN, but also the broader potential of SARM1 inhibition to address additional neurological diseases. We are inspired to advance this potential therapy for millions of patients around the world.” CIPN is a common nerve-damaging side effect of chemotherapy that affects the hands and feet. Symptoms include burning or shooting pain, loss of temperature and tactile sensation, muscle weakness, and impaired fine motor skills. A significant number of cancer patients receive high-risk chemotherapy (e.g., taxanes, platinum, vinca alkaloids), develop CIPN, and subsequently discontinue or reduce chemo regimen due to the disease. “For too long, millions of cancer patients have found themselves in the difficult position of experiencing painful symptoms while receiving their cancer treatment,” said Dr. Robert Coleman, Gynecologic Oncologist, Texas Oncology, and Chief Medical Officer of Vaniam Group; and one of the country’s preeminent gynecologic oncologists. “Unfortunately, the severity of these symptoms has led many patients to either curtail or completely stop their treatment regimens. I’m pleased that a potential treatment for CIPN is advancing that could at last address this condition.” About SIR2501 SIR2501 is a first-in-class allosteric inhibitor of SARM1, a key driver of nerve damage in diseases such as CIPN and amyotrophic lateral sclerosis (ALS). By binding SARM1 away from its active site and maintaining the enzyme in an inactive state, SIR2501 is designed to protect nerves and prevent degeneration, while avoiding potential adverse effects observed with orthosteric inhibitors. SIR2501 has demonstrated strong neuroprotective effects in multiple preclinical models, and global Phase 1b/2 clinical trials evaluating SIR2501 in patients with CIPN and ALS are ongoing. About Sironax Sironax is a clinical-stage biotechnology company developing transformative therapies for neurodegenerative, inflammatory and immunologic, metabolic, and rare diseases. Founded in 2017, the company has built a diverse pipeline of programs by targeting contributors of aging, degeneration, metabolic dysfunction, and inflammation. Sironax is conducting clinical studies with SARM1 inhibitor SIR2501, NAMPT activator SIR4156, and RIPK1 inhibitor SIR9900, in addition to ongoing preclinical research. The company was named to the 2025 Endpoints 11 list of the most promising biotech startups. For more information, visit sironax.com . Forward-looking Statements This press release contains forward-looking statements related to SIR2501’s potential benefits and clinical progress, which are subject to risks and uncertainties. Actual outcomes may differ based on technical, regulatory, and market factors. Contact Information Investors/Media Erik Kopp Executive Director, Corporate Communications and Investor Relations PR@sironax.com Business Development Yan Lu, Ph.D. Senior Director, Business Development and Corporate Strategy BD@sironax.com