Open-label extension strengthens breadth of XanaMIA study
In April, Actinogen announced that it had commenced the OLE phase of its XanaMIA Phase IIb/III pivotal study for lead candidate Xanamem for the treatment of mild-to-moderate AD. As a reminder,
the XanaMIA Phase IIb/III study is designed to assess mild-to-moderate AD patients
(with elevated blood levels of phosphorylated Tau-181, or pTau-181, at baseline) across 35 sites in the US and Australia.
| Exhibit 1: XanaMIA Phase IIb/III study overview |
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| Source: Actinogen presentation, February 2026. Note: NIA-AA, National Institute on
Aging – Alzheimer's Association; CDR-SB, Clinical Dementia Rating Scale – Sum of Boxes. |
In the double-blinded portion of the trial, patients are randomised to take 10mg of
Xanamem or a placebo once daily for 36 weeks. Actinogen recruited the final (247th)
participant in the study in December 2025, and the last participant’s final evaluation
visit is anticipated in September 2026, leading to a top-line primary efficacy readout
projected for November 2026. The primary endpoint is the drug’s effect on AD progression
using the FDA-recognised Clinical Dementia Rating – Sum of Boxes (CDR-SB), a comprehensive
scale of functional capacities. Notably, this scale was also used as the primary endpoint
to support the FDA approval of Eisai and Biogen’s Leqembi (lecanemab) in AD.
The OLE portion of the study (XanaMIA-OLE) is open to all former and current XanaMIA
participants who completed the randomised phase of the study. Subjects will receive
10mg of active Xanamem once daily for up to 25 months of treatment, and there is no
placebo control group. The OLE study is designed to evaluate safety and a limited
number of efficacy endpoints (such as CDR-SB, other measures of cognition, and parameters
relating to daily living activities), which may be potentially supportive for future
regulatory approval applications. The first participant in the OLE portion received
treatment in late March. Encouragingly, the company reports that there has been enthusiastic
initial uptake for the OLE study in its first month, with 15 of the first 17 patients
(88%) who completed the randomised portion of XanaMIA study having agreed to take
part in the OLE phase.
| Exhibit 2: XanaMIA open-label extension study design |
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| Source: Actinogen presentation, May 2026 |
We anticipate that regulators (eg the FDA) will review an eventual Xanamem marketing
application more favourably should the OLE (non-blinded) extension phase provide supportive
longer-term safety data (beyond the 36-week period studied during the XanaMIA randomised
trial phase).
XanaMIA supported by biomarker specific design and positive interim data
As explained in a prior note, XanaMIA’s study design was supported by a subset analysis among patients with elevated pTau-181 at baseline from Actinogen’s previous XanADu study (n=185) in patients with AD. This analysis showed statistically significant improvements
versus the placebo on the CDR-SB scale in this group, suggesting that Xanamem’s potential
cognitive or disease-slowing effects may be sensitively detected by the CDR-SB endpoint.
| Exhibit 3: Exhibit 3 - XanADu study results in patients with high pTau-181 |
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| Source: Actinogen presentation, February 2026 |
Further, on 30 January, Actinogen reported that the independent data monitoring committee (DMC) for the
study recommended for the trial to continue without modifications after completing
its interim analysis of study data. The external DMC considered unblinded safety and
efficacy data (reflecting Xanamem or placebo treatment) from c 37% of the expected
final dataset, including data from 136 participants with one or more efficacy data
points and 52 study participants who had completed the full 36 weeks of treatment.
The DMC concluded that the unblinded safety and efficacy data it reviewed support
the continuation of the study towards its conclusion, expected in or around November
2026. The DMC analysis was based on a highly confidential process designed to preserve
the statistical power of the trial, and it included an interim futility analysis.
This analysis was based on an assessment of whether the likelihood of the study meeting
the primary efficacy endpoint was near nil (ie if ‘futility’ criteria are met). Fortunately,
the interim XanaMIA efficacy results surpassed the futility thresholds, meaning the
DMC determined that the available data did not justify an early termination of the
study for futility. While the DMC would not comment on any possible positive signals
of efficacy, the lack of futility is a positive signal from the DMC that, after having
examined a meaningful proportion of efficacy data, it determined there is sufficient
evidence of potential therapeutic activity to justify permitting the study to proceed
to completion. We also note that the DMC did not identify any major safety concerns,
which is reassuring but not surprising given that more than 400 patients have already
been treated with the drug across multiple trials.
XanaMIA is designed to serve as one of the two pivotal trials required to support
a regulatory approval application for Xanamem in the treatment of AD. The company
anticipates that in the event of positive top-line results (expected to be released
in November), it will seek accelerated approval pathways with regulators, including
the FDA, to potentially seek an expedited approval process without requiring completion
of the second study. Our base case continues to assume that Xanamem will require two
pivotal studies prior to commercialisation, and we anticipate the earliest possible
approval and launch (following the conclusion of the second study) will occur in CY30.
As explained in our prior note, we expect this second pivotal trial to start in CY27 and, like XanaMIA, to be a
well-controlled, two-arm study assessing 10mg of Xanamem versus a placebo, although
it will be larger and will span multiple countries in addition to Australia and the
US. We believe the study will include sites in Europe and China and in total will
enrol c 700 patients (vs c 247 for XanaMIA) and we expect the primary efficacy endpoint
will measure treatment over a longer duration (such as 52 weeks after baseline), compared
to the 36-week duration for XanaMIA.
Completed capital increase lengthens runway past XanaMIA study completion
In late February Actinogen announced the successful completion of its A$16.8m capital raise (first
announced on 2 February), which consisted of a A$12.0m (gross) share placement (primarily from sophisticated
and professional investors), along with A$4.8m raised from existing investors through
a share purchase plan offer at the same financial terms as the placement (A$0.042
per share). The share placement included the subscription for A$500,000 by Actinogen’s
CEO, Dr Steven Gourlay, as well as the subscription for A$167,000 from other directors
of the company. The participation by the company’s CEO can be perceived as a vote
of confidence in the prospects of the company and its lead pipeline molecule, Xanamem.
The proceeds are primarily being directed towards continuation and completion of the
ongoing XanaMIA Phase IIb/III study (and the OLE phase), with a portion being allocated
towards working capital, R&D and manufacturing activities, and costs of the offer.
Considering this cash position, Actinogen expects its funds on hand to last into mid-CY27,
well past the completion of the XanaMIA study.
Financials
Actinogen’s H126 financials (six months ending December 31) showed an operating loss of A$11.4m, and an operating
cash burn rate of A$7.1m, inclusive of the receipt of A$5.5m in government R&D tax
incentives (RDTI) from the Australian Tax Office (ATO) during the period. Excluding
the R&D tax rebates, the operating burn rate would have been A$12.6m. The largest
driver of the burn rate is the company’s R&D expenditure, which is primarily driven
towards ongoing progression of the XanaMIA study and came in at A$8.9m during the
period. This was up from A$4.6m in the prior year period, given the increased total
number of XanaMIA subjects being actively dosed and monitored during the period (as
the study’s enrolment continued to increase in the period). As stated earlier, the
company received a A$5.5m RDTI payment from the ATO in October and used A$3.1m of
the proceeds to pay down its debt to Endpoints Capital.
The company’s most recent Appendix 4C statement (three months ending 31 March) reflected similar trends. The company reported a three-month
operating cash burn rate of A$5.5m, which included an A$1.9m RDTI rebate payment received
in February (and which corresponded to the company’s FY25 R&D activities). Excluding
the RDTI, the operating cash burn rate would have been A$7.4m, driven largely by the
A$6.2m in R&D spending (predominantly directed towards the XanaMIA study) over the
period.
Actinogen’s cash balances were bolstered by the A$16.8m (or A$16.0m, net of financing
costs) capital raise described above, and by the company in January 2026 taking a
A$4.3m loan from the Endpoints Capital facility (secured against its expected RDTI
rebate for FY26). As result, the company finished the period with a gross cash position
of A$21.5m. We expect that this cash position will be sufficient to fund the company’s
operations into mid-CY27, which is past the conclusion of the XanaMIA study (expected
in or around November 2026). This cash cushion provides the company with optionality
and operating flexibility to secure a global licensing deal for Xanamem should the
results from the XanaMIA study be positive.
Given the 4C statement and H126 financials, we have made minor adjustments to our
FY26 and FY27 estimates. We have reduced our FY26 net R&D spending estimate to A$19.4m
(from A$20.0m previously), and have mildly reduced our FY26 free cash outflow estimate
to A$19.0m (from A$19.6m previously). For FY27, we have reduced our net R&D spending
and free cash outflow estimates to A$27.8m and A$35.9m, respectively, from A$28.6m
and A$37.6m, previously. As a reminder, we expect the company’s second (and larger)
Phase III AD study for Xanamem to begin in H1 CY27, which drives our expectations
for a significant increase in R&D spending and free cash outflow in FY27.
| Exhibit 4: Changes to Actinogen forecasts |
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| Source: Edison Investment Research |
We expect the company’s gross cash position (A$21.5m at end-March) to be sufficient
to fund Actinogen’s operations into mid-CY27 (end-FY27). With the XanaMIA top-line
readout scheduled for November, this extended cash runway provides the company with
greater flexibility to negotiate a potentially transformative licensing deal following
the conclusion of XanaMIA should the top-line efficacy results be favourable. We also
note that there remains the possibility for targeted regional licensing transactions
over the next six to nine months ahead of the XanaMIA readout, which would depend
on market conditions and strategic considerations for potential suitors or licensors.
Altogether, the positive interim analysis provides the company with additional flexibility
to assess potential deals both before and after the XanaMIA top-line readout, although
we believe the attainment of a global comprehensive deal after the study’s conclusion
remains the most likely outcome.
Our model continues to assume that Actinogen will also start a Phase IIb/III study
for Xanamem in major depressive disorder (MDD) in CY27, although AD remains the company’s
priority, and we do not expect material further clinical development in MDD until
the XanaMIA study is completed (and the second Phase III AD study has commenced).
Our cash utilisation estimates for FY27 and beyond would be reduced if the company
postpones further clinical development in MDD. We also continue to project that Actinogen
will receive R&D research tax credits (which correspond to up to 48.5% of R&D and
related costs incurred in the prior fiscal year) from the Australian government.
We maintain our potential commercialisation timeline for Xanamem in AD to CY30 and
for a potential launch in CY29 for Xanamem in the MDD indication, but plan to revise
our assumptions as the company provides further guidance on development in this indication.
As our base-case scenario does not assume a commercial out-licensing partnership for
Xanamem, our model continues to project that Actinogen will independently fund Xanamem
towards approval and commercialisation. We continue to estimate the total projected
additional future funding needed to launch Xanamem in AD and MDD and obtain recurring
operating profitability will be A$225m.
