Some scattered notes and thoughts;
Many thanks to Dr. Missling for the A3-71 P1 data results. I look forward to the imminent Avatar data.
Also, for making the effort to organize subject verb agreement which makes it easier for English speaking people to understand and relax while listening. It is appreciated.
When we look at the safety P-1 data between the two compounds A-371 looks, from the profile extremely well tolerated, so we had much broader therapeutic dose range.
We dosed in Anavex2-73 up to 60 mg in the phase one and in Anavex3-71 we dosed up to 200mg so it’s a broader range in Anavex3-71.
Dr. Missling said there were factors that could not be anticipated that delayed the data releases such as;
Flights have been delayed, communication was impacted, sampling, shipments and so forth but he believes everything is on track and especially on Avatar is coming around soon.
With Orphan Drug Designation in FTD we’re planning a quasi Basket Trial where we put 3 indications in one study and we see how the drug effect is working on the longitudinal side and compared to placebo. So it will be a placebo controlled study where we look at all three indications at the same time.
The protocol will likely include separately, patients with Alzheimer’s disease, Alzheimer’s pathology, patients with Schizophrenia and Frontal Temporal Dementia. Among them we will make sure we will capture what is considered state of art; Patients who are declining, patients who are homogenous in the pathology which is why we stated it will be a biomarker driven inclusion criteria as well as in the outcome study.
Biomarkers;
A3-71 and A2-73 are both sigma one agonist receptors.
Both have agonistic affinity with the M-1 muscarinic receptor, known to be CNS beneficial activators.
A2-73 has stronger antagonistic affinity on the M-2 receptor.
A3-71 has a higher affinity to the S1 in vitro than 2-73. We don’t know yet if that translates into higher biological activity. Affinity level does not always translate to a higher activity.
A3-71 was good at removing Tau pathology which is what FTD is considered to be.
A3-71 is very good at reducing abeta and inflammation in a triple transgenic animal model.
Could also go into the clinic with depression and other rare diseases later.
Planning on doing a study with eeg/erp, the Consortium is currently exploring these as surrogate biomarkers.
As well as blood and CSF biomarkers.
Looking at neuro-filament light change, NFL. Plasma and serum concentration, glutamate and other related… my recording dropped out here for a few seconds.
Biomarkers may show earlier separation in FTD and Alzheimer’s studies. Hoping to have cohort data on 3-71 in 2nd half of this year IF everything goes smoothly.
3-71 has a broad therapeutic window from 5mg to about 160mg, which is broader than 2-73 where dosing was up to 60mg in the P-1.
Dosing higher doesn’t necessarily mean better, however.
Anavex 3-71 is very well tolerated.
