Changes to the XanaMIA protocol reduce cost by AUD 30 million over the next two years and speed time to initial results while preserving the 36-week design and trial endpoints.

UK sites added to the XanaCIDD trial of cognitive impairment associated with depression, due to report results mid-2024.

The current, FDA-approved three-arm trial was designed to confirm the safety, pro-cognitive and clinical benefits of Xanamem^® and explore two dose levels. The new design keeps the same endpoints, 36-week treatment length and other features except for the 5 mg dose group.

Actinogen Chief Medical Officer, Dr Dana Hilt, commented:
"Removal of the 5 mg dose group, while deferring the dose-ranging aspect of the Xanamem program to the next, likely Phase 3 trial, does not detract from the strong confirmatory value of the trial design. The trial retains its ability to robustly demonstrate the clinical benefit of Xanamem in patients with Alzheimer's disease."

Operationally, the trial has been streamlined with the following modifications:

• New: 10 mg or placebo daily vs. 10 mg, 5 mg or placebo previously
• New: 220 patients vs. 330 patients previously but still studying patients with the elevated blood pTau biomarker (the same group shown to have a large Xanamem clinical effect in the previous Phase 2a biomarker trial)
• New: Australian sites to enroll the first 100 patients vs. simultaneous global site activation previously
• New: Initial efficacy and safety results from an administrative interim analysis when approximately 100 patients reach 24 weeks of treatment vs. unspecified previously.

Collectively these changes reduce trial costs significantly and increase forecast receipts from Australian R&D tax incentive cash refunds by focusing on Australian R&D activities in the near term. Net forecast savings between now and June 2025 will be in the order of $30 million compared to the original plan.

The new implementation plan assumes that expansion of the XanaMIA trial will occur when potentially new, positive clinical data is received from the XanaCIDD trial by mid-2024 and/or the redesigned XanaMIA interim analysis, planned for H1 2025.

Xanamem's promising safety profile has been demonstrated in more than 300 people to date.

The XanaMIA Phase 2b trial will finalize Australian clinical site start up activities as soon as possible with patient recruitment expected before the end of the year.

General Business Update

1.    XanaCIDD Phase 2a trial

The Company is also pleased to advise that it has expanded the XanaCIDD Phase 2a randomized clinical trial in patients with cognitive impairment associated with depressive disorder (CIDD) from Australia to include UK sites, which have commenced screening.

The XanaCIDD Phase 2a depression trial is a double-blind, six-week proof-of-concept, placebo-controlled, parallel group design trial in 160 patients with both depression and cognitive impairment. Patients are evenly randomized to receive Xanamem 10 mg once daily or placebo, in some cases in addition to their existing antidepressant therapy, and effects on cognition and depression are assessed.

Results of the XanaCIDD trial are anticipated by mid-2024.

Leading neuroscience authority and cognition expert, Professor Paul Maruff,^[1] said:
"Xanamem is one of the few drugs being developed for neurodegenerative diseases such as Alzheimer's disease or neuropsychiatric diseases such as major depressive disorder, that throughout development has shown consistent and substantial benefits to cognition.  These have been observed in healthy healthy older adults, and in adults with mild dementia.  This evidence provides an excellent foundation for the full development of Xanamem."  

2.    Neuroscience webinar

The Company conducted a highly informative 'Fireside Chat' webinar on 31 August 2023 with Professor Paul Maruff and CMO, Dr Dana Hilt, who discussed and reviewed progress in the evaluation of cognition, Alzheimer's disease and Xanamem's clinical data.

Click on the following link to access the neuroscience webinar recording:
https://www.youtube.com/watch?v=yBvReLbauhg

3.    Rights issue capital raising

ACW successfully closed an AUD 10 million rights issue capital raising from existing shareholders and selected new shareholders on September 4, 2023.