Lighthouse Pharmaceuticals to Present Phase 2 SPRING Trial of LHP588, a Next-Generation Gingipain Inhibitor for the Treatment of

P. gingivalis -Positive Alzheimer’s Disease, at CTAD 2025 Novato CA — November 26, 2025 — Lighthouse Pharmaceuticals, a clinical-stage biopharmaceutical company pioneering precision medicine to address major unmet medical needs, announced a poster presentation at the Clinical Trials on Alzheimer’s Disease (CTAD) 2025 conference in San Diego, California on Wednesday, December 3, 2025, from 7:15 A.M. - 5:30 P.M (P230). The poster, titled “The SPRING Trial: Treatment of P. gingivalis–Positive Mild to Moderate Alzheimer’s Disease with the Second-Generation Gingipain Inhibitor LHP588,” highlights the rationale, design, and previous clinical data supporting the ongoing Phase 2 SPRING trial (NCT06847321) . The National Institute on Aging (NIA) recently awarded $49.2 million to Lighthouse to conduct the SPRING trial, underscoring the data supporting this mechanism of action. The SPRING trial (Stopping PRogression of P. gINGivalis-Positive AD with Gingipain Inhibition) builds upon the findings of a previous clinical study, the GAIN trial of atuzaginstat, which demonstrated that treatment with the gingipain inhibitor slowed cognitive decline in mild-moderate Alzheimer’s patients with P. gingivalis detected in saliva. The second-generation compound, LHP588, was developed to overcome limitations of the earlier molecule, offering improved safety and target engagement, with once-daily oral dosing. “LHP588 represents a significant advancement in our effort to target a bacterial driver of Alzheimer’s disease with a high-precision oral medication,” said Michael Detke, MD, PhD, Chief Medical Officer at Lighthouse Pharmaceuticals. “By focusing on P. gingivalis–positive patients and integrating biomarker-guided selection we can maximize the benefit to patients with mild-moderate AD, for which there are no other disease-modifying therapies. We are excited to be enrolling and expanding the number of patients across the United States in 2026.” Key Highlights Phase 1 Results : LHP588 was well-tolerated in a single- and multiple-ascending dose study, with excellent safety and no dose limiting adverse events. Pharmacokinetics : Superb oral bioavailability and cerebrospinal fluid exposure consistent with once daily oral dosing; no infusions necessary. Phase 2 Design : The SPRING trial will enroll 300 patients with mild-to-moderate Alzheimer’s disease (MMSE 12-24) who test positive for P. gingivalis in saliva and have elevated plasma p-tau217, or other biomarkers of AD pathology. The design leverages learnings from the clinical study of the first-generation molecule, atuzaginstat, which demonstrated 57% slowing of decline on ADAS-cog in this population, without adverse amyloid-related imaging abnormalities (ARIA). Endpoints : Cognitive outcomes (ADAS-Cog11), functional and global scales (CDR-SB, ADCS-ADL, MMSE), and biomarkers including P. gingivalis load, whole brain atrophy, and plasma p-tau217 levels.

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