tazbentetol (SPG302) / Spinogenix - LARVOL DELTA

Efficacy and Safety of Tazbentetol in ALS Participants (clinicaltrials.gov) - P2/3 | N=430 | Not yet recruiting | Sponsor: Spinogenix | Initiation date: Mar 2026 ➔ Oct 2026

Trial initiation date • Amyotrophic Lateral Sclerosis • CNS Disorders

Spinogenix presented new data at the 2026 Alzheimer's Association International Conference (AAIC) showing that tazbentetol…produced durable cognitive improvement in patients with mild-to-moderate Alzheimer disease (AD) who continued treatment for up to 84 weeks under a compassionate use program following a completed phase 2a trial (NeurologyLive) - "Overall, tazbentetol was safe and well tolerated, with no treatment-related adverse events or serious adverse events, and plasma pharmacokinetics were similar to those seen in phase 1 healthy volunteers. At the 300 mg dose, SMMSE improved significantly during the DBPC period and remained significant and durable through the 24-week OLE, with a 2.20-point (SEM, 0.8) increase over baseline. CDR-SB improved by 0.8 points at 24 weeks and by 1.5 points at 40 weeks with continued 300 mg dosing, and ADCS-ADL improved by 4.4 points from baseline at 40 weeks."

P2a data • Alzheimer's Disease

SPG302 Mitigates Diabetic Retinal Neuropathy and Inner Retinal Damage in a Genetic Mouse Model of Diabetes. (PubMed, Exp Eye Res) - "SPG302 treatment effectively preserved retinal integrity by reversing these changes. Thus, SPG302 has therapeutic potential for protecting the inner retina and mitigating DRN in diabetes."

Journal • Preclinical • CNS Disorders • Diabetes • Diabetic Neuropathy • Diabetic Retinopathy • Glaucoma • Metabolic Disorders • Ophthalmology • Pain • Retinal Disorders • BAX • DLG4 • LEP • LEPR • SYP

Rapid and Durable Improvements in Cognitive and Neurophysiological Outcomes in Tazbentetol treated mild-moderate AD patients (AAIC 2026) - No abstract available

Clinical

Spinogenix to Present Preclinical Results at ARVO 2026 Demonstrating Neuroprotective Effects of Tazbentetol in Glaucoma and Diabetic Retinopathy Models (PRNewswire) - "Mice in each study received daily tazbentetol (30mg/kg i.p.) or control treatment for eight weeks, during which elevations in IOP (MB mouse) and blood sugar (db/db mouse) were monitored to confirm disease. Mice treated with tazbentetol were found to keep retinal ganglion cells alive in both disease models – the neurons whose death ultimately causes blindness. Beyond survival, the drug preserved synaptic connectivity in the retina, protected the optic nerve, and critically, translated these cellular gains into measurable improvements in visual function. In each model, tazbentetol reversed decreases in pERG amplitude (a reflection of RGC viability) and in the db/db mouse tazbentetol also shortened the latency of the pVEP (a reflection of improved RGC axon conduction)."

Preclinical • Diabetic Retinopathy • Glaucoma

Spinogenix Receives U.S. FDA Fast Track Designation for Tazbentetol for the Treatment of ALS (PRNewswire) - "Milestone Follows Recent Announcement of Phase 2a Results Showing Preliminary Evidence that Tazbentetol's First in Class Synaptic Regenerative Mechanism Slowed Rate of Decline in ALS Patients."

Fast track • Amyotrophic Lateral Sclerosis

Neuroprotective effects of Tazbentetol (SPG302) in mouse models of glaucoma and diabetic retinal neuropathy: preservation of visual function and protection of the inner retina (ARVO 2026) - "Since the retina is an extension of the brain and retinal synapse loss occurs in major causes of blindness, we tested the ability of Tazbentetol to prevent damage in mouse models of glaucoma and diabetic retinal neuropathy. Results show that daily dosing of Tazbentetol can minimize inner retinal synaptic and cellular loss in mouse models of these diseases, and partially preserve retinal function, supporting the potential of this new neuroprotective therapy."

Preclinical • Diabetic Retinopathy • Glaucoma • Ophthalmology • Retinal Disorders • RBPMS • SYP

Glutamate Metabotropic Receptors-Linked Postsynaptic Density Proteins: An Emergent Hub for Antipsychotics' Regulation of Synaptic Plasticity and Metaplasticity. (PubMed, Biomolecules) - "Notably, novel agents that enhance spinogenesis by acting at the level of PSD proteins, such as SPG302, may open promising avenues for therapeutics aimed at restoring synaptic integrity...Emerging strategies, such as allosteric modulators of mGluRs, aim to rebalance synaptic signaling in treatment-resistant schizophrenia. This review synthesizes how PSD proteins and mGluRs interact in schizophrenia, exploring their potential as druggable targets for novel therapies."

Journal • Review • CNS Disorders • Mental Retardation • Psychiatry • Schizophrenia

Efficacy and Safety of Tazbentetol in ALS Participants (clinicaltrials.gov) - P2/3 | N=430 | Not yet recruiting | Sponsor: Spinogenix | Phase classification: P2 ➔ P2/3

Phase classification • Amyotrophic Lateral Sclerosis • CNS Disorders

SPG302-SCZ-201: Study of SPG302 in Adults With Schizophrenia (clinicaltrials.gov) - P2 | N=32 | Active, not recruiting | Sponsor: Spinogenix | Recruiting ➔ Active, not recruiting | Trial primary completion date: Dec 2025 ➔ Mar 2026

Enrollment closed • Trial primary completion date • CNS Disorders • Psychiatry • Schizophrenia

Efficacy and Safety of Tazbentetol in ALS Participants (clinicaltrials.gov) - P2 | N=336 | Not yet recruiting | Sponsor: Spinogenix

New P2 trial • Amyotrophic Lateral Sclerosis • CNS Disorders

Developing Topics. (PubMed, Alzheimers Dement) - "Once-daily treatment with the novel synaptogenic small molecule, SPG302, is safe and well tolerated in AD participants over the course of 28 weeks was associated with early signs of cognitive improvements."

Clinical • Journal • Alzheimer's Disease • CNS Disorders

Extension Study of Participants From SPG302-ALZ-101 (clinicaltrials.gov) - P2 | N=12 | Terminated | Sponsor: Spinogenix | N=24 ➔ 12 | Trial completion date: Dec 2026 ➔ Oct 2025 | Enrolling by invitation ➔ Terminated | Trial primary completion date: Sep 2026 ➔ Jul 2025; patients treated on compassionate use program

Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Alzheimer's Disease • CNS Disorders

Extension Study of Participants From SPG302-ALS-001 (clinicaltrials.gov) - P2 | N=16 | Terminated | Sponsor: Spinogenix | Trial completion date: Aug 2026 ➔ Aug 2025 | Enrolling by invitation ➔ Terminated | Trial primary completion date: May 2026 ➔ Jun 2025; patients treated through compassionate use program

Trial completion date • Trial primary completion date • Trial termination • Amyotrophic Lateral Sclerosis • CNS Disorders

Completion of a Phase 2 trial evaluating safety and efficacy of the synaptic regenerative small molecule SPG302 in participants with mild-to-moderate Alzheimer's disease (CTAD 2025) - No abstract available

Clinical • P2 data • Alzheimer's Disease • CNS Disorders

Clinical results of a Phase 2a trial evaluating the synaptogenic small molecule SPG302 in ALS participants (ALS-MND 2025) - P1 | "SPG302 was safe and well tolerated with drug exposure profiles similar to healthy volunteers. Baseline NfL measures showed prediction of outcome, and trends toward improved ECAS scores were observed. During the DBPC period, ALS signature deficits in resting state EEG power were significantly improved with SPG302 compared to placebo and showed a regional correspondence to affected brain regions."

Clinical • P2a data • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Orthopedics • Plasma NfL • TARDBP

Preliminary Phase 2 Data Support Therapeutic Development of Synaptic Regenerative Drug SPG302 in ALS (NeurologyLive) - "In terms of efficacy, preliminary data showed that 82% of SPG302-treated patients demonstrated stable or improved rate of disease progression at the end of treatment, as assessed through the ALS Functional Rating Scale-Revised (ALSFRS-R). When compared with historical controls from the PRO-ACT database (n = 299), patients on the investigational drug exhibited a 76% slower rate of decline through 6 months."

P2a data • Amyotrophic Lateral Sclerosis

Spinogenix Announces Publication of Preclinical Study Demonstrating Neuroprotective Effects of SPG302 in a Model of Glaucoma (PRNewswire) - "In the study, three-month-old mice were treated daily with SPG302 for eight weeks following microbead injection to induce elevated IOP. SPG302 administration significantly improved RGC survival and axonal integrity while preserving visual function as assessed by electroretinography, a clinically translatable measure of retinal function."

Preclinical • Glaucoma

SPG302 protects retinal ganglion cells and preserves visual function by preserving synaptic activity in a mouse model of glaucoma. (PubMed, Exp Eye Res) - "SPG302 treatment effectively preserved synaptic integrity by reversing these changes. These findings highlight the therapeutic potential of SPG302 for protecting RGCs and preserving vision by modulating synaptic activity in glaucomatous neurodegeneration."

Journal • Preclinical • CNS Disorders • Glaucoma • Ocular Inflammation • Ophthalmology • Optic Neuritis • Pain • DLG4 • SYP

Findings From First Cohort of SPG302 in Phase 2 Alzheimer Disease Trial: Sharron Gargosky, PhD (NeurologyLive) - P2 | N=24 | NCT06427668 | Sponsor: Spinogenix | "SPG302...currently being investigated in a phase 2 trial for its safety and potential efficacy among adult patients with mild-to-moderate Alzheimer disease (AD) in Australia. In the first completed cohort of the study, findings showed that once-daily treatment with SPG302 was safe and well tolerated in patients with AD over the course of 28 weeks, revealing early signs of cognitive improvements. Coauthor Sharron Gargosky, PhD, and colleagues, presented these results at the recently concluded 2025 Alzheimer’s Association International Conference, held July 27-30, in Toronto, Canada....She also discussed the clinically meaningful cognitive improvements reported, with early effects apparent as soon as 1 week and sustained over a 24-week open-label extension. Overall, she highlighted that these results support further development of SPG302 both as a monotherapy and as an adjunctive therapy to standard of care in AD."

P2 data • Alzheimer's Disease

SPG302-SCZ-201: Study of SPG302 in Adults With Schizophrenia (clinicaltrials.gov) - P2 | N=32 | Recruiting | Sponsor: Spinogenix | Trial completion date: Oct 2025 ➔ Feb 2026 | Trial primary completion date: Jun 2025 ➔ Dec 2025

Trial completion date • Trial primary completion date • CNS Disorders • Psychiatry • Schizophrenia

Intermediate-size Patient Population Expanded Access Protocol (clinicaltrials.gov) - P=N/A | N=0 | Available | Sponsor: Spinogenix

New trial • Amyotrophic Lateral Sclerosis • CNS Disorders

Study of SPG302 in Healthy Volunteers and ALS Participants (clinicaltrials.gov) - P1 | N=88 | Completed | Sponsor: Spinogenix | Active, not recruiting ➔ Completed | Trial completion date: Dec 2025 ➔ Jun 2025

Trial completion • Trial completion date • Amyotrophic Lateral Sclerosis • CNS Disorders

Extension Study of Participants From SPG302-ALS-001 (clinicaltrials.gov) - P2 | N=16 | Enrolling by invitation | Sponsor: Spinogenix | Not yet recruiting ➔ Enrolling by invitation

Enrollment open • Amyotrophic Lateral Sclerosis • CNS Disorders

Spinogenix Announces Full Enrollment in its Phase 2 Trial Evaluating SPG302 as a First-in-Class Synaptic Regenerative Therapy for Alzheimer's Disease (PRNewswire) - "Spinogenix...announced full enrollment of its Phase 2 clinical trial in Australia evaluating SPG302 for the treatment of people with Alzheimer's disease (AD)....Spinogenix is completing a randomized, double-blind, placebo-controlled Phase 2 study of SPG302 (NCT06427668) to assess the safety, tolerability, and clinical efficacy of SPG302 in adult participants with mild-to-moderate AD. Two dose cohorts are being evaluated in a total of 24 participants. The first cohort has completed 24 weeks of treatment (inclusive of a double-blind phase and an open label extension period). Results from this cohort will be presented at the Alzheimer's Association International Conference (AAIC) in Toronto on July 27-31, 2025. In parallel, the U.S. Food and Drug Administration (FDA) cleared Spinogenix's Investigational New Drug (IND) application for SPG302 for the treatment of people with AD."

Enrollment closed • IND • P2 data • Alzheimer's Disease