Ann Morgan:
Neuroplasticity is a hallmark of abnormal brain development. Weak or non-functioning synapsis are attacked by this protein called C1q, which is the initiating molecule for the classical complement pathway. When this protein is tacked on the synapsis microglial cell will get recruited to the synapsis and engulf the synapse or that it will start at the formation of the MAC complex leading to cell lysis...
Ann Morgan:
Neuroplasticity is a hallmark of abnormal brain development. Weak or non-functioning synapsis are attacked by this protein called C1q, which is the initiating molecule for the classical complement pathway. When this protein is tacked on the synapsis microglial cell will get recruited to the synapsis and engulf the synapse or that it will start at the formation of the MAC complex leading to cell lysis. In neurodegenerative disease, we believe that this pathway gets reactivated aberrantly, leading to the destruction of the synapsis, as well as neuronal cell loss.
ANX005 is a monoclonal antibody targeting the protein C1q, I mentioned earlier. We have founded to have excellent penetration into the CNS, so in the study eligible subjects are enrolled and being dosed biweekly for 24 weeks.
Rajeev Kumar:
This was an open-label study and patients who were initially dosed with a 23 hour initial loading infusion and then dosed every two weeks for a period of 24 weeks. Then there was a 12 week off drug assessment and safety phase in which we looked at the persistent effects both clinically as well as on biomarkers.
What we saw, overall, the drug was well tolerated. There were some adverse events, predominantly those individuals who had a high baseline ANA, so there seemed to be an autoimmune effect. We also found that in general there was stability of the clinical function, so there wasn’t deterioration and this is true and good compared to a similarly disease and age-matched control cohort in observational studies, such as from the TRACK HD cohort. We also found that from a biomarker perspective, overall, neurofilament light remained quite stable, which is good because we would expect over time there should be gradual increase in this biomarker.
We found that there seemed to be separation and there were two different groups. The group that had a higher baseline level, the C4A to C4 complement ratio compared to those who had a lower level. Those individuals with a higher ratio had a higher baseline level of complement activation, suggesting that neuroinflammation may be playing a greater role in the progression and pathogenesis of disease. Indeed, in this upper half of the patient population we saw that those patients were seemingly responders with improvement in the cUHDRS, as well as the total functional capacity score. These people improved greater than their baseline and this was statistically significant compared to those people who had low baseline C4A, C4 ratios. This improvement was seen soon after drug therapy began and this continued not only to the end of dosing, but continued into the safety phase up to three month post-dosing.
Ann Morgan:
Yes, I would also add that in the later study when we’re looking at other longitudinal study patients who have high baseline C4A tend to, the patient, had worse prognosis of without treatment and so we are very pleased to see that these are the patient that will actually showing improvement. We are also looking forward to leverage this precision medicine strategy to photo development ANX005.
