Xanamem (emestedastat) / Actinogen Medical - LARVOL DELTA

XanaMIA: Effect of 10 mg Xanamem on Dementia Due to Alzheimer's Disease (clinicaltrials.gov) - P2 | N=220 | Active, not recruiting | Sponsor: Actinogen Medical | Recruiting ➔ Active, not recruiting | Trial completion date: Dec 2025 ➔ Oct 2026 | Trial primary completion date: Dec 2025 ➔ Oct 2026

Enrollment closed • Trial completion date • Trial primary completion date • Alzheimer's Disease • CNS Disorders • Dementia • p-tau181

Actinogen Medical presents Alzheimer’s and depression program at BIO-Europe 2025 (BiotechDispatch) - "Chief Executive Officer Dr Steven Gourlay and Chief Commercial Officer Andy Udell are representing the company in Vienna, meeting with global pharmaceutical and biotechnology leaders, investors and potential partners to discuss the pivotal XanaMIA Phase 2b/3 trial in Alzheimer’s disease and the growing global interest in novel approaches that regulate cortisol in the brain...Actinogen’s presence follows a successful meeting with the U.S. FDA, confirming the development pathway for XANAMEM toward U.S. marketing approval and the completion of screening in the company’s pivotal Alzheimer’s trial. Interim results are expected in early 2026, with topline data anticipated mid-Q4 2026...An open-label extension phase will follow in 2026 to gather long-term safety data."

P2/3 data • Trial status • Alzheimer's Disease

Emestedastat, a selective 11β-HSD1 inhibitor, demonstrates positive effects on depression in a phase 2 trial of moderate Major Depressive Disorder (ECNP 2025) - "These data support the hypothesis that decreasing CNS cortisol may be beneficial to patients with MDD. Emestedastat represents a novel pharmacological approach to the treatment of depression via steroidogenesis inhibition and merits further study."

P2 data • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry

Actinogen achieves agreement with the FDA in a Type C meeting on the manufacturing, clinical and nonclinical activities required for a future US marketing approval of Xanamem for Alzheimer’s disease (GlobeNewswire) - "Key understandings include the: ‘Regulatory starting materials‘ for the commercial manufacturing of Xanamem (emestedastat) drug substance...Design of one additional, well-controlled, pivotal (phase 3) trial to support a positive XanaMIA pivotal trial; Single emestedastat dose design (10 mg vs placebo) for the planned pivotal Phase 3 trial; Number of people to be treated with Xanamem to be described in the New Drug Application (NDA) – that is, the makeup of the planned safety database consistent with FDA guidelines; Small number of ancillary clinical pharmacology trials to be conducted; Nonclinical studies required to further characterize the metabolism and excretion pathways of Xanamem."

FDA event • Trial status • Alzheimer's Disease

The company confirmed that in a recent Type C meeting, conducted by written response with the FDA’s Neurology-I Division, regulators endorsed Actinogen’s streamlined development plan. (BiotechDispatch) - "Among the key outcomes were clarity on the regulatory starting materials for Xanamem’s commercial manufacture, the design of an interim analysis for the ongoing XanaMIA trial, and agreement on the structure of a single pivotal Phase 3 trial. The FDA also backed a simplified trial design using a single 10 mg daily dose of Xanamem compared with placebo, along with a limited set of ancillary pharmacology and nonclinical studies...It also paves the way for submissions to other regulators, including the European Medicines Agency in 2026 and subsequently the UK Medicines and Healthcare products Regulatory Agency."

EMA filing • FDA event • Alzheimer's Disease

The company’s XanaMIA Phase 2b/3 trial is currently underway in Australia and the US, testing Xanamem in 220 patients with mild to moderate Alzheimer’s confirmed by biomarker analysis. (BiotechDispatch) - "Initial results from an interim analysis are expected in January 2026, with final outcomes anticipated later that year."

P1 data • Alzheimer's Disease

XanaMIA phase 2b/3 Alzheimer's disease trial progress (PRNewswire) - "Enrolment in the pivotal XanaMIA phase 2b/3 Alzheimer's disease (AD) clinical trial has passed 55% as at the end of July 2025...A planned safety and efficacy futility interim analysis of all available data by an independent Data Monitoring Committee will occur in January 2026....Final results for the full enrolment of 220 participants are expected in Q4 2026."

DSMB • Enrollment status • P2/3 data • Alzheimer's Disease

A novel oral treatment for Alzheimer's: Actinogen's pivotal trial currently recruiting participants in the US (PRNewswire) - "Actinogen Medical Limited...is encouraging individuals and their loved ones affected by Alzheimer's disease to take part in a groundbreaking clinical trial that could transform the way we treat this devastating condition...The trial is enrolling people diagnosed with mild to moderate Alzheimer's disease, offering them a chance to participate in cutting-edge research aimed at stabilizing the cognitive and functional decline of Alzheimer's...The trial involves taking a single pill once a day of Xanamem or matching placebo ('sugar pill') and a series of clinic visits for the assessment of Alzheimer's progress. It does not involve frequent brain scans or complicated procedures such as lumbar puncture....All participants at the end of the XanaMIA trial are eligible for Actinogen's open-label extension trial of active Xanamem for up to 24 months. This extension trial will open to completed XanaMIA participants in early 2026."

Trial status • Alzheimer's Disease

Xanamem a Selective 11ß-HSD1 Inhibitor Has Positive Effects on Depression in a Phase 2 Trial of Moderate Major Depressive Disorder (APA 2025) - "These data support the hypothesis that decreasing CNS cortisol may be beneficial to patients with MDD. Xanamem represents a novel pharmacological approach to the treatment of depression and merits further study."

P2 data • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry

Targeting Brain Cortisol: Xanamem Shows Promise in Depression and Alzheimer Disease (Psychiatric Times) - "Actinogen investigated Xanamem in patients with residual depression who after at least 6 weeks of treatment with an antidepressant medication...Participants, who had Hamilton Depression Rating Scale (HAM-D) scores of 17 or higher as well as demonstrated cognitive impairment, were randomized to placebo or 10 mg of Xanamem daily for 6 weeks, followed by a 4-week blinded observation period. 'At the end of 10 weeks, there was a statistically significant separation with the treated patients doing better as compared to the placebo'"

Clinical data • Alzheimer's Disease • Depression

Actinogen provides pivotal Alzheimer’s trial enrolment update and other business news (GlobeNewswire) - "Actinogen Medical Limited...announces that its Alzheimer’s disease phase 2b/3 trial has now enrolled 60 participants and expects to reach 100 by the end of this quarter. That milestone will trigger an interim analysis of available trial data by an independent Data Monitoring Committee approximately 6 months later. Final results for the full 220 participants are expected in Q4 2026....A similar Type C meeting for Alzheimer’s disease (AD) will be held with the FDA’s Neurology Division later in 2025 to define the optimal path to a marketing approval."

Enrollment status • FDA event • P2/3 data • Alzheimer's Disease

PLASMA PTAU181 PREDICTS CLINICAL PROGRESSION IN MILD ALZHEIMER'S DISEASE IN A RANDOMIZED CONTROLLED TRIAL. (ADPD 2025) - "Together, these data suggest elevated plasma pTau181 may have utility for patient enrichment in future AD trials of patients with mild AD. Enrichment in this way may reduce sample size, cost, and duration of clinical trials. Xanamem showed evidence of potentially clinically meaningful benefits in these patients that will be further explored."

Clinical • Alzheimer's Disease • CNS Disorders • p-tau181

Role of 11β-Hydroxysteroid Dehydrogenase and Mineralocorticoid Receptor on Alzheimer's Disease Onset: A Systematic Review. (PubMed, Int J Mol Sci) - "However, clinical trials, including those involving ABT-384 and Xanamem, have produced mixed results, with no substantial cognitive improvements despite effective enzyme inhibition...Ongoing research is focusing on optimizing 11β-HSD1 inhibitors, identifying biomarkers for patient selection, and investigating combination therapies to enhance treatment efficacy. Ultimately, 11β-HSD1's role in AD presents a promising therapeutic target, but further studies are required to fully understand its potential in managing the disease."

Journal • Review • Alzheimer's Disease • CNS Disorders • Inflammation

Actinogen announces peer-reviewed clinical pharmacology manuscript for Xanamem (emestedastat) published in Clinical Pharmacology in Drug Development journal (PRNewswire) - "Actinogen Medical Limited...announces that the publication of its most recent peer-reviewed journal article entitled Clinical Pharmacology and Approach to Dose Selection of Emestedastat...The review confirms the utility of the 10 mg daily dose of Xanamem being used in current clinical trials. From a drug development perspective, it demonstrates the value of using central pharmacodynamics (PD), including positron emission tomography (PET) and computerized cognitive testing, to supplement pharmacokinetic (PK) and endocrine-based PD for determining the target dose range for clinical efficacy testing...The XanaMIA Phase 2b/3 Alzheimer's disease trial is a double-blind, 36-week treatment, placebo-controlled, parallel group design trial in 220 patients with mild to moderate AD and progressive disease...Initial results from an interim analysis of the first 100 participants are anticipated in Q4 2025 and final results H2 2026."

Clinical • P2/3 data • Alzheimer's Disease

Actinogen announces new and unique nonproprietary name of 'emestedastat' for Xanamem (PRNewswire) - "Actinogen Medical Limited...announces that the World Health Organization (WHO) has granted the nonproprietary name of 'emestedastat' to Actinogen for its Xanamem/UE2343 once-a-day small molecule in accordance with the WHO's Procedure for the Selection of Recommended International Nonproprietary Names (INN) for Pharmaceutical Substances...XanaMIA Alzheimer's disease phase 2b/3 trial sites enrolling in the USA and Australia...Final results are expected in the second half of 2026 with interim results anticipated in Q4 this year."

Commercial • P2/3 data • Alzheimer's Disease

Drug Development. (PubMed, Alzheimers Dement) - "This series of trials demonstrates that the optimal dose of Xanamem can be selected based on CNS PET occupancy data coupled with pharmacodynamic endocrinology and quantitative cognition testing. Pro-cognitive and potentially disease modifying effects were observed at doses consistent with high CNS target occupancy. Xanamem is now in larger Phase 2 clinical outcome trials in MDD and mild/mod AD."

Journal • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Endocrine Disorders • Inflammation • Mental Retardation • Psychiatry • p-tau181

Actinogen randomizes first US participant in XanaMIA phase 2b/3 Alzheimer's disease trial (PRNewswire) - "Actinogen Medical Limited...announces that the first participant was randomized and treated Friday in the United States in the XanaMIA phase 2b/3 clinical trial in patients with biomarker-positive mild to moderate Alzheimer's disease (AD). The trial is designed to select 220 participants with a progressive clinical profile, determined by elevated levels of the blood biomarker pTau181. It measures the effects of a Xanamem 10 mg daily dose versus placebo over a 36-week treatment period on multiple clinical endpoints of function and cognition....An interim analysis is planned for Q3 2025 when approximately 100 patients reach 24 weeks of treatment, with final results anticipated in H2 2026."

P2/3 data • Trial status • Alzheimer's Disease

Xanamem® in Adults With Major Depressive Disorder and Impaired Cognition (XanaCIDD) (clinicaltrials.gov) - P2 | N=167 | Completed | Sponsor: Actinogen Medical | Active, not recruiting ➔ Completed

Trial completion • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry

Positive Xanamem biomarker trial published in the Journal of Alzheimer's Disease demonstrating potential Xanamem efficacy in patients with elevated blood pTau (PRNewswire) - P2b | N=220 | XanaMIA (NCT06125951) | Sponsor: Actinogen Medical | "Highlights of the publication include...Patients with elevated pTau181 had much more rapid progression than patients with lower levels in four key clinical endpoints: ADCOMS (p<0.001), CDR-SB (p<0.001), MMSE (p=0.12) and ADAS-Cog14 (p=0.19); In the 34 patients with elevated pTau181 a potentially large and clinically meaningful Xanamem treatment effect compared to placebo was seen in the CDR-SB (LS[2] mean difference 0.6 units, p=0.09) and positive trends were observed in a Neuropsychological Test Battery of cognition (LS mean difference 1.8 units, p=NS)...The XanaMIA trial is anticipated to report interim results mid-2025 and final results in 2026."

P2b data • Alzheimer's Disease • CNS Disorders

Development of Xanamem, an isoform 1 specific inhibitor of 11-βHSD, as a procognitive and disease modifying treatment for mild/moderate Alzheimer’s disease. A pharmacodynamic and biomarker driven approach. (AAIC 2024) - "This series of trials demonstrates that the optimal dose of Xanamem can be selected based on CNS PET occupancy data coupled with pharmacodynamic endocrinology and quantitative cognition testing. Pro-cognitive and potentially disease modifying effects were observed at doses consistent with high CNS target occupancy. Xanamem is now in larger Phase 2 clinical outcome trials in MDD and mild/mod AD."

Biomarker • PK/PD data • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Inflammation • Mental Retardation • Psychiatry • p-tau181

Plasma pTau181 Predicts Clinical Progression in a Phase 2 Randomized Controlled Trial of the 11β-HSD1 Inhibitor Xanamem® for Mild Alzheimer's Disease. (PubMed, J Alzheimers Dis) - "This trial demonstrates that elevated plasma pTau181 identifies participants more likely to have progressive AD and is a suitable method for enrichment in AD clinical trials. Xanamem treatment showed evidence of potential clinically meaningful benefits."

Journal • P2 data • Alzheimer's Disease • CNS Disorders • p-tau181

Xanamem® in Adults With Major Depressive Disorder and Impaired Cognition (XanaCIDD) (clinicaltrials.gov) - P2 | N=160 | Active, not recruiting | Sponsor: Actinogen Medical | Recruiting ➔ Active, not recruiting

Enrollment closed • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry

First patient treated in Actinogen's XanaMIA phase 2b Alzheimer's disease trial (PRNewswire) - "Actinogen Medical Limited...announces that the first patient has been randomized and treated in the XanaMIA phase 2b clinical trial in patients with biomarker-positive mild to moderate Alzheimer's disease (AD). This represents the culmination of the site and screening setup phase of the trial when patient pre-screening for elevated levels of the pTau blood biomarker commenced at multiple clinical sites. The XanaMIA trial is a double-blind placebo-controlled randomized trial design which will enrol 220 participants with mild to moderate AD and elevated levels of plasma pTau. The trial measures the effects of a Xanamem 10 mg daily dose versus placebo on safety and its ability to preserve cognition and function over a 36-week treatment period....An interim analysis is planned for mid-2025 when approximately 100 patients reach 24 weeks of treatment, with final results anticipated in H1 2026."

P2b data • Trial status • Alzheimer's Disease

The Importance of PET Imaging to Understanding Whole-Body Cortisol Metabolism in Alzheimer's Disease. (PubMed, J Alzheimers Dis) - "In this current issue, high regional brain occupancy of Xanamemtrademark, determined by [11C]TARACT PET imaging of 11β-HSD1, in cognitively normal individuals and mild cognitive impartment/Alzheimer's disease (AD) patients is presented. In the future, comprehensive kinetic modeling using arterial sampling for occupancy studies, and whole-body PET imaging of 11β-HSD1 enzyme levels, in combination with stable isotope studies of cortisol metabolism, can provide broad insight into enzyme levels and activity in AD and other relevant diseases."

Journal • Alzheimer's Disease • CNS Disorders • Dementia

Xanamem® in Adults With Major Depressive Disorder and Impaired Cognition (XanaCIDD) (clinicaltrials.gov) - P2 | N=160 | Recruiting | Sponsor: Actinogen Medical | Trial primary completion date: Mar 2024 ➔ Jul 2024

Trial primary completion date • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry