GEN Pharmaceuticals Reports Positive Phase 1 Results for Novel Alzheimer's Drug SUL-238
Key Insights
GEN Pharmaceuticals (search) announced positive Phase 1 trial results for SUL-238, a first-in-class mitochondria (search)-directed drug candidate for Alzheimer's disease (search) and other neurodegenerative conditions.
The study demonstrated that single oral doses of 50-2000 mg were safe and well-tolerated in 53 healthy elderly volunteers, with favorable pharmacokinetics and high brain penetration.
SUL-238 showed impressive cerebrospinal fluid penetration rates of 21.1% at 2 hours and 74.2% at 8 hours post-dose, supporting its potential for treating brain disorders.
GEN Pharmaceuticals (search) has announced positive results from its Phase 1 clinical trial of SUL-238, a novel mitochondria (search)-directed drug candidate for Alzheimer's disease (search) and other neurodegenerative conditions. The findings, presented at the Alzheimer's Association International Conference 2025 in Toronto, demonstrate that the first-in-class oral therapy is safe and well-tolerated while achieving significant brain penetration in healthy elderly volunteers.
Phase 1 Trial Design and Results
The single oral ascending dose Phase 1 study was a first-in-human, randomized, double-blind, placebo-controlled trial conducted in three parts involving 53 healthy elderly adults. Part 1 evaluated six dose cohorts ranging from 50 to 2000 mg orally in 23 participants. Part 2 investigated the pharmacokinetics of a single 1000 mg oral dose in 10 healthy elderly adults, while Part 2B assessed food effects using a crossover design with a 2000 mg dose in 20 participants.
The trial results showed that single oral doses of 50-2000 mg of SUL-238 were safe and well-tolerated across all dose levels. No adverse effects limited dose escalation, and adverse event rates were comparable between SUL-238 and placebo groups. All reported adverse events were classified as mild or moderate in severity.
Favorable Pharmacokinetic Profile
SUL-238 demonstrated a favorable pharmacokinetic profile with a mean terminal elimination half-life of 0.86-3.80 hours and time to maximum plasma concentration of 0.50-1.39 hours. Under fed conditions, maximum plasma concentration and area under the plasma concentration-time curve decreased by 50% and 60%, respectively.
Most notably, the drug showed impressive cerebrospinal fluid penetration, with CSF-to-plasma percentages of 21.1% (±6.6%) at 2 hours post-dose and 74.2% (±46.0%) at 8 hours post-dose. This high brain penetration is particularly significant for treating neurodegenerative diseases (search) that affect the central nervous system.
Novel Mechanism of Action
SUL-238 is a hibernation-derived small molecule that targets mitochondria (search), often referred to as the cell's "powerhouse." The drug supports mitochondrial bioenergetics through complex I/IV (search) activation and has demonstrated improved mitochondrial function in rodent models of neurodegenerative, cardiovascular, and renal diseases, as well as aging.
The compound crosses the blood-brain barrier and represents a first-in-class approach to addressing mitochondrial dysfunction in neurodegeneration. GEN licenses SUL-238 from Dutch biotech company Sulfateq BV (search) specifically for neurodegenerative disease applications.
Company Leadership Perspectives
Abidin Gülmüş, Chairman of GEN, expressed enthusiasm about the results, stating: "We are very encouraged by these promising first-in-human results, marking an important step forward in our mission to address the underlying biology of Alzheimer's disease (search)."
Nadir Ulu, MD, PhD, Vice President of R&D at GEN, added: "With its excellent safety and PK profile in this Phase 1 trial, combined with robust preclinical data, SUL-238 represents a strong candidate for further clinical development to meet the critical unmet needs in neurodegenerative diseases (search), including Alzheimer's disease (search)."
Development Partnership
The collaboration between GEN Pharmaceuticals (search), Turkey's leading specialty pharmaceutical company founded in 1998, and Sulfateq BV (search) represents a strategic partnership in neurodegenerative disease research. Sulfateq is an early-stage Dutch biotech company that has developed the SUL-compounds class of small molecules designed to maintain mitochondrial health through strategic collaborations with academic and industrial research centers.