Actinogen Medical (ASX:ACW) said an independent Data Monitoring Committee (DMC) has recommended its ongoing XanaMIA pivotal trial of Xanamem in mild-to-moderate Alzheimer’s disease continue without changes, following an interim safety and efficacy/futility review. Company executives said the outcome increases their confidence ahead of planned topline results in November, while also outlining a new equity raising intended to fund operations beyond that readout.
Independent DMC review supports continuing the XanaMIA trial
Management described the DMC’s latest assessment as a key de-risking milestone for the program. According to the presentation, the external committee had access to unblinded trial data, while no one inside the company had access to unblinded information.
Hilt added the DMC review covered “the totality of the data,” including patients with more than six months of treatment and 52 patients who had completed the entire study—about 37% of total trial data. The committee was chaired by neurologist Dr. Hans Moebius, who Hilt said developed and led approval of Namenda for Alzheimer’s disease.
On safety, the company said Xanamem has been safe and well tolerated to date, with no serious adverse events attributed to or associated with the drug. Executives also emphasized that the trial cleared the pre-specified safety and efficacy/futility hurdles.
What the company said about Xanamem’s mechanism and prior data
During the webinar, Actinogen reiterated its rationale that Xanamem (also referred to as emustadostat) is designed to selectively inhibit 11-beta-HSD1 in the brain, reducing locally generated brain cortisol while leaving systemic cortisol normal. The company argued this approach could address Alzheimer’s disease biology beyond amyloid and tau.
Hilt highlighted previously presented and published work supporting target engagement, describing PET scan evidence showing reduced binding of a probe to 11-beta-HSD1 in the presence of Xanamem at doses including 5 mg and 10 mg. He called this “gold standard” evidence that the drug reaches the brain and binds its target.
Hilt also discussed earlier clinical signals:
- A pilot Alzheimer’s study (XanaDU) subset analysis in patients with elevated p-Tau181, where he described a treatment effect on the CDR Sum of Boxes scale over three months (Cohen’s d about 0.4; mean change 0.6).
- A Phase II depression study in treatment-resistant major depressive disorder patients, where he cited separation by weeks six to 10 and a reported Cohen’s d of 0.64.
Company speakers positioned these data as part of the basis for the current XanaMIA design.
Trial design, upcoming milestones, and open-label extension
The company said the XanaMIA Phase IIb/III study is a 10 mg once-daily Xanamem trial versus placebo, with 36 weeks of observation and 247 enrolled patients across U.S. and Australian sites. Inclusion criteria include a clinical Alzheimer’s diagnosis plus elevated blood p-Tau181. The primary endpoint is CDR Sum of Boxes, with key secondary endpoints including activities of daily living and a cognitive test battery.
Hilt said the company plans to initiate an open-label extension study of 10 mg, expected to start around the end of Q1 or Q2, and offered to participants after they complete the main trial and a four-week follow-up. Management clarified that patients cannot move directly from the blinded pivotal study into the open-label study without completing the main trial period. The company said the extension is intended to gather longer-term safety and tolerability data and to monitor whether any observed benefit persists.
Executives also referenced planned scientific conference activity and a peer-reviewed publication related to the Phase II depression trial, as well as plans to engage with the European Medicines Agency in 2026.
Regulatory path and partnering strategy
Hilt said the company has held a Type C meeting with the U.S. FDA and reached agreement on key points for remaining activities needed for a future NDA submission. He stated the FDA indicated one additional pivotal study of 10 mg versus placebo would be required, without the need for a dose-ranging study versus placebo. The company said it is planning the outline and operational preparation for that subsequent study while limiting spend until the current topline results are available.
Management said it intends to focus resources on the Alzheimer’s program and, after the November readout, plans to engage with major global strategic partners, while remaining open to smaller regional deals if terms are favorable. The CEO also noted a “long shot” possibility that European regulators could consider an expedited approval approach, but emphasized there is no guarantee.
AUD 12 million placement and share purchase plan to fund beyond November
Actinogen also announced a capital raise comprised of an AUD 12 million non-underwritten placement priced at AUD 0.42 per share, with a follow-on share purchase plan (SPP) targeting approximately AUD 5 million (and potentially more depending on demand). The company said there are no attaching options. The SPP is available to eligible shareholders for up to AUD 30,000 per holding.
Chief Financial Officer Will (surname not provided in the transcript) said the company ended 31 December with AUD 6.5 million in cash and subsequently raised AUD 4.3 million in non-dilutive funding by borrowing against its accrued R&D rebate. He said that, combined with the placement and expected SPP proceeds, the company’s pro forma cash balance as at 31 December was close to AUD 30 million, and that the funding is intended to carry the company beyond the November results.
The company said directors collectively committed AUD 667,000 to the placement, including AUD 500,000 from CEO Steve (surname not provided), who said his total personal cash commitment to the company is about AUD 2.5 million.
Management said proceeds will be used primarily to complete the XanaMIA trial, open the open-label extension program, support other R&D and manufacturing activities, and provide working capital. The company also referenced potential future cash inflows from option exercises and the R&D tax incentive.
About Actinogen Medical (ASX:ACW)
Actinogen Medical Limited, a biotechnology company, develops therapies for neurological and neuropsychiatric diseases associated with dysregulated brain cortisol in Australia. It is developing Xanamem, an inhibitor of the 11ß-HSD1 enzyme, which is in Phase 2 clinical trials that achieves target engagement in the central nervous system, depression with cognitive impairment, Alzheimer's disease, and anxiety, sleep, and behavioral problems in fragile X syndrome. The company was formerly known as Actinogen Limited and changed its name to Actinogen Medical Limited in November 2015.
