One readout this fall would answer four questions at once, and reprice more than one company. A framework for reading ARO-MAPT before the data arrives.
Do you know of anything that supports the likelihood of a successful ARO-MAPT readout in the coming month, given that no clinical data are yet available to the company or anyone else. Is there any evidence suggesting that the strong NHP and other preclinical results are likely to translate into positive Phase 1 data, beyond just the company’s track record with other drugs in their pipeline?
Secondly, Any idea why Vangaard and Blackrock are decreasing their holdings?
On translation, there's no direct evidence yet, because there isn't any. What exists is indirect. The transferrin receptor pathway ARO-MAPT uses isn't unvalidated, Denali and Roche have both taken TfR-based brain shuttles into development, and Genentech has published primate data showing systemically delivered oligonucleotides reaching the CNS. I walk through the delivery science in more detail in The Last Mile to the Brain if you want the fuller picture.
Worth noting that September is a lower bar than people assume. Management has guided to safety and total tau knockdown in healthy volunteers, not benefit in patients. Target engagement is a pharmacology question, and pharmacology translates from primates more reliably than efficacy does.
On Vanguard and BlackRock, I'd read little into it. Those are overwhelmingly index and quantitative strategies, so the moves track fund flows and rebalancing, not a view on Arrowhead.
Thanks very much for sharing — interesting read.
Do you know of anything that supports the likelihood of a successful ARO-MAPT readout in the coming month, given that no clinical data are yet available to the company or anyone else. Is there any evidence suggesting that the strong NHP and other preclinical results are likely to translate into positive Phase 1 data, beyond just the company’s track record with other drugs in their pipeline?
Secondly, Any idea why Vangaard and Blackrock are decreasing their holdings?
Thanks for reading, and both are fair questions.
On translation, there's no direct evidence yet, because there isn't any. What exists is indirect. The transferrin receptor pathway ARO-MAPT uses isn't unvalidated, Denali and Roche have both taken TfR-based brain shuttles into development, and Genentech has published primate data showing systemically delivered oligonucleotides reaching the CNS. I walk through the delivery science in more detail in The Last Mile to the Brain if you want the fuller picture.
Worth noting that September is a lower bar than people assume. Management has guided to safety and total tau knockdown in healthy volunteers, not benefit in patients. Target engagement is a pharmacology question, and pharmacology translates from primates more reliably than efficacy does.
On Vanguard and BlackRock, I'd read little into it. Those are overwhelmingly index and quantitative strategies, so the moves track fund flows and rebalancing, not a view on Arrowhead.