I'm not sure they'll be able to reduce toxicity much with IMET2.0 as I believe the Grade 3/4 SAEs are primarily a function of the drug doing its job. However, they may be able to reduce SAEs by way of spreading the dose out over time. Said differently, a pill version of IMET might not reduce toxicity per unit of drug, but the ability to dose in smaller quantities (via pill) over time may be very advantageous over the current 9.4 mg/kg dose that is administered in a 2-hour transfusion window. This might be why they're focusing on the conversion of IMET to an orally administered medicine.
The ability to combine with other drugs is going to be key to A) helping the most patients, and B) maximizing shareholder value. The dose adjusting flexibility that comes with a pill version might be key to future combinations.
Thoughts on IMET2.0 toxicity improvements...
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Hoosier Investor
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Thoughts on IMET2.0 toxicity improvements...
Last edited by Hoosier Investor on Thu Nov 18, 2021 9:16 pm, edited 1 time in total.
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Hoosier Investor
- Posts: 128
- Joined: Thu Jun 18, 2020 5:48 pm
Re: Thoughts on IMET2.0 toxicity improvements...
Further thought along these lines.......
The ability to deliver the drug orally (smaller quantities over time) may allow for a more potent version of IMET with expectations of SAEs that are similar to today's IMET results. Such an approach might enable improved overall efficacy without a corresponding increase in SAE events.
A pill version (available in different sizes) would also provide more flexibility in managing the patient's treatment. The patient wouldn't necessarily have to skip one (or more) infusions like they do today. They could stay on the drug but shift to a lesser dose as a means of managing the side effects.
The ability to deliver the drug orally (smaller quantities over time) may allow for a more potent version of IMET with expectations of SAEs that are similar to today's IMET results. Such an approach might enable improved overall efficacy without a corresponding increase in SAE events.
A pill version (available in different sizes) would also provide more flexibility in managing the patient's treatment. The patient wouldn't necessarily have to skip one (or more) infusions like they do today. They could stay on the drug but shift to a lesser dose as a means of managing the side effects.
Re: Thoughts on IMET2.0 toxicity improvements...
If they use antibody-labeled liposomes to target the oligo (e.g. the original GRN 163) on cancer cells instead of dumping most of it into off-target cells, there would clearly be a MASSIVE decrease in toxicity.
But there won't be an "oral imetelstat"... MAIA's 6-thio-dG is oral, but that's because it's just one base.
If JNJ had bothered to use their massive drug-screening capability to find a synthetic small-molecule drug that matched the binding sites of imet, maybe that could have been an oral drug. But there's zero sign of anyone putting any major resources into new telomerase inhibitors. We're just coasting on ancient work by Sergei and the 2015 Shay Lab papers on 6-thio-dG.
But there won't be an "oral imetelstat"... MAIA's 6-thio-dG is oral, but that's because it's just one base.
If JNJ had bothered to use their massive drug-screening capability to find a synthetic small-molecule drug that matched the binding sites of imet, maybe that could have been an oral drug. But there's zero sign of anyone putting any major resources into new telomerase inhibitors. We're just coasting on ancient work by Sergei and the 2015 Shay Lab papers on 6-thio-dG.