Release Date: August 07, 2024
For the complete transcript of the earnings call, please refer to the full earnings call transcript.
Positive Points
- Alector Inc (ALEC, Financial) has a strong cash position of $503.3 million, extending its runway through 2026.
- The company is on track for the AL002 Phase 2 trial INVOKE-2 data readout in Q4 2024.
- AL002 has shown robust target engagement and increased microglial signaling in Phase 1 studies.
- The FDA granted breakthrough therapy designation to Latozinemab for the potential treatment of FTD with GRN limitations.
- Alector Inc (ALEC) introduced the Alector Brain Carrier (ABC) platform, enhancing drug delivery across the blood-brain barrier.
Negative Points
- The INVOKE-2 trial has seen MRI findings resembling amyloid-related imaging abnormalities (ARIA), particularly in APOE4 homozygotes.
- Enrollment in the PROGRESS-AD global Phase 2 clinical trial of AL101 is ongoing, indicating potential delays.
- The company faces challenges in demonstrating clinical efficacy for AL002, which may not reach the 24 centiloid level necessary for clinical efficacy seen in anti-amyloid antibodies.
- The long-term extension study for INVOKE-2 remains blinded, potentially delaying the full understanding of the drug's efficacy and safety.
- Alector Inc (ALEC) has not yet disclosed which programs in its earlier portfolio will advance next, creating uncertainty about future developments.
Q & A Highlights
Q: On TREM2, do you mind just reminding everybody what proportion of data from participants out to 48 weeks and 96 weeks and somewhere in between you expect in this upcoming readout? And also do you plan on rolling over APOE4 homozygotes that were in the placebo group to your long-term extension study?
A: All of the patients, all the completers, which we expect to be around 250, will complete 48 weeks of treatment. About half of those will have 72 weeks of treatment and about a third will have 96 weeks of treatment. Our LTE remains blinded to original treatment assignment, allowing us to collect meaningful data on biomarkers, safety, and clinical outcomes. We are rolling over the placebo group, but it does not include APOE4 homozygotes anymore due to more severe MRI changes resembling ARIA in this group.
Q: On Latozinemab, can you just clarify what exactly does it mean that the FDA would consider plasma and CSF PGRN as confirmatory?
A: If we have a positive result on the primary clinical outcome measure, the FDA would consider effects on plasma and CSF progranulin levels as confirmatory evidence, supplementing the potential clinical effects of Latozinemab. This does not mean the biomarkers would be surrogates for the clinical outcome measure. However, if we see directional effects on these biomarkers, it could support an accelerated approval approach.
Q: How should we be thinking about patients enrolling in a long-term extension study for INVOKE-2 in terms of tolerability and efficacy?
A: We are very pleased that 95% of eligible patients have decided to roll over into the LTE. We will include some of the LTE data in our sensitivity analysis when we lock the database later this year. There haven’t been any significant safety signals beyond the MRI signal resembling ARIA and a small number of infusion reactions.
Q: Are you able to say whether the mean amyloid PET centiloid level differed between the two populations in terms of cognitive impairment versus dementia?
A: We don’t have the data broken down by MCI and mild AD regarding the centiloid levels. We reported the aggregate centiloid levels. The baseline characteristics reported included everyone up to that point for which we had data, as the trial was fully enrolled.
Q: What would you think is the expectation for centiloid reduction in INVOKE?
A: We wouldn’t be surprised to see amyloid lowering given the MRI findings resembling ARIA. However, this mechanism goes beyond amyloid clearance. We are restoring microglial function, which has broader beneficial effects on brain health. Therefore, we are not solely focused on reaching the 24 centiloid level necessary for clinical efficacy seen with anti-amyloid antibodies.
Q: Can you give us an idea of what to expect for the first data release next quarter for TREM2? What’s the bar for moving this program forward into a later-stage study?
A: The press release will include primary clinical outcomes, safety, and relevant biomarkers. The decision to advance will be based on a combination of clinical, functional, and biomarker readouts showing consistency in slowing disease progression. Directional effects consistent with biomarker outcomes would be considered a win.
Q: Regarding safety monitoring, is it safe to assume that ARIA-like observations have been minimized due to the protocol changes?
A: After dropping APOE4s and adding MRI surveillance, the incidence and severity of ARIA have come down. We are exploring whether starting at a lower dose and titrating more slowly in the LTE could further reduce the ARIA signal.
Q: Could you describe the tissues or cell types where CD98 is expressed and outline any theoretical risks associated with targeting CD98?
A: CD98 is expressed in endocrine tissues, the pancreas, the kidney, genitalia, and a little in the skin. In the brain, it is expressed higher in microglia and astrocytes and lower in neurons outside of the endothelial cells. We will monitor for any adverse effects in these tissues.
Q: Can you remind us when the potential AbbVie opt-in payment might be booked?
A: AbbVie has 90 days to decide if they are opting in after we share the proof-of-concept study package at the end of Q4 this year. The payment would be expected towards the end of Q1 or early Q2.
Q: How does the analytical methodology for INVOKE-2 compare with others in Alzheimer's disease?
A: The proportional MMRM method allows us to use all data collected in the common close design trial, increasing power and potentially enabling statistical significance at a smaller effect size. This method has been used in other Alzheimer's trials and is particularly helpful in our biomarker-rich study design.
For the complete transcript of the earnings call, please refer to the full earnings call transcript.
