Tazbentetol Shows Durable Cognitive Benefit Through 84 Weeks in Alzheimer Disease

Spinogenix presented new data at the 2026 Alzheimer's Association International Conference (AAIC) showing that tazbentetol, an investigational oral synaptic regenerative therapy, 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. Group-level cognitive scores remained improved over baseline beyond one year of continuous treatment.^1,2

Phase 2a trial design and topline results

The completed phase 2a trial (NCT06427668) was a multicenter study that randomized 24 patients with mild-to-moderate AD (MMSE, 16-26) 2:1 to placebo or active tazbentetol at 150 mg or 300 mg once daily. The design included a 28-day double-blind, placebo-controlled (DBPC) period, followed by a 24-week open-label extension (OLE) during which all participants received 300 mg, and a long-term follow-up period extending to 12 months; efficacy assessments included standard Mini Mental State Exam (SMMSE), Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB), the ADCS-Activities of Daily Living Inventory (ADCS-ADL), resting-state EEG, and P300 auditory event-related potentials.²

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. Quantitative EEG measures of AD-related cortical slowing also improved significantly at 300 mg, but not 150 mg, during the DBPC period, including a 36% reduction in the theta/beta ratio and a 43% reduction in a global slowing index, changes investigators described as consistent with more normalized cortical network activity.

Extended treatment and case study findings

Beyond the controlled trial period, Spinogenix presented a case study of a 72-year-old woman with mild AD who initially presented with short-term memory loss, anomia, and impaired social skills. Within three months of starting 300 mg tazbentetol, her caregiver reported she had regained the ability to read books, follow movies, and recall storylines; this corresponded with a 4- to 6-point increase in SMMSE and a 2.5-point decrease in CDR-SB by three months, with further CDR-SB improvement by 24 weeks and continued SMMSE improvement over baseline through her most recent visit at 81 weeks.¹

"We are excited to share these extended data with the Alzheimer's community, demonstrating the potential of tazbentetol as an efficacious and well-tolerated treatment," Stella Sarraf, PhD, chief executive officer and founder of Spinogenix, said in a statement.¹ Steven E. Arnold, MD, professor of neurology at Harvard Medical School and a member of Spinogenix's Scientific Advisory Board, added, "I look forward to supporting the company's efforts in planning their next Alzheimer's trial to advance a first-in-class synaptic regenerative therapy in the field."¹

About tazbentetol

Tazbentetol is designed to trigger neurons to form new axospinous glutamatergic synapses, based on the premise that AD is fundamentally a synaptopathy; the compound received its World Health Organization International Nonproprietary Name in December 2025.^3,4 Beyond AD, tazbentetol is furthest along in amyotrophic lateral sclerosis (ALS), where it holds Orphan Drug designation from the FDA and EMA and FDA Fast Track designation.⁵

In a phase 2a ALS trial (NCT05882695) reported in December 2025, 82% of 23 treated patients showed a stable or improved rate of decline on the ALS Functional Rating Scale-Revised at end of treatment, with an average 76% slower rate of decline through 6 months compared with historical controls from the PRO-ACT database.⁶ The FDA has also authorized an Expanded Access Cost Recovery Program for tazbentetol in ALS (NCT07088159).⁷ A separate phase 2 trial in schizophrenia (NCT06442462) completed enrollment of 32 patients in early 2026.⁸

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REFERENCES
1. Spinogenix Reports Positive Data on Alzheimer's Patients Who Continued Treatment With Tazbentetol For Up To 84 Weeks. News release. Spinogenix, Inc. July 14, 2026. Accessed July 24, 2026. https://www.prnewswire.com/news-releases/spinogenix-reports-positive-data-on-alzheimers-patients-who-continued-treatment-with-tazbentetol-for-up-to-84-weeks-302825473.html
2. Brew B, Priest L, Gargosky S, Vanderklish P, Erickson C, Pedapati E, Sarraf S. Rapid and Durable Improvements in Cognitive and Neurophysiological Outcomes in Tazbentetol Treated Mild-Moderate AD Patients. Presented at: Alzheimer's Association International Conference; July 2026; London, England. ClinicalTrials.gov identifiers: NCT06427668, NCT06833281.
3. Spinogenix Announces World Health Organization Approval of 'tazbentetol' as International Non-Proprietary Name for SPG302. News release. Spinogenix, Inc. December 1, 2025. Accessed July 24, 2026. https://spinogenix.com/press-release/spinogenix-announces-world-health-organization-approval-oftazbentetol-as-international-non-proprietary-name-for-spg302/
4. About Spinogenix. Spinogenix, Inc. Accessed July 24, 2026. https://spinogenix.com/about/
5. Spinogenix Receives U.S. FDA Fast Track Designation for Tazbentetol for the Treatment of ALS. News release. Spinogenix, Inc. Accessed July 24, 2026. https://www.prnewswire.com/news-releases/spinogenix-receives-us-fda-fast-track-designation-for-tazbentetol-for-the-treatment-of-als-302762461.html
6. Spinogenix Presents Topline Phase 2a Clinical Trial Results for SPG302, a First-in-Class ALS Treatment. News release. Spinogenix, Inc. November 2025. Accessed July 24, 2026. https://www.spinogenix.com/spinogenix-presents-topline-phase-2a-clinical-trial-results-for-spg302-a-first-in-class-als-treatment/
7. SPG302. ALS/MND drugs in development database. ALS/MND International Alliance. Accessed July 24, 2026. https://www.als-mnd.org/support-for-pals-cals/drugs-in-development/spg302/
8. Spinogenix Completes Enrollment in Phase 2 Clinical Trial of Tazbentetol for Schizophrenia Treatment. News release. Spinogenix, Inc. Accessed July 24, 2026. https://spinogenix.com/press-release/spinogenix-completes-enrollment-in-phase-2-clinical-trial-of-tazbentetol-for-schizophrenia-treatment/