RE: Bone Marrow Toxicity, Brain malignancies?30 Jan 2026 13:26
Interesting and intelligent quesitions.
As regards, fibrotic targets due to prior anthracycline treatment, it'll be interesting to see whether this side effect is reduced in previously untreated patients. The breakdown of side effects vs prior treatment hasn't been presented yet but it is exacty the sort of detail I'm wanting to see (also, for example, side effects vs cancer indication/metastasis site). Hopefully it will be included when the Phase 1 trial is written up in a peer-reviewed article, but there's always the AGM as an opportunity for asking detailed questions in person.
As regards crossing the blood-brain barrier (BBB)...
Temozolomide - molecular weight: 194.15 Da
Doxorubicin - molecular weight: 543.52 Da
Faridoxorubicin - molecular weight: 816.8 Da
Faridoxorubicin without doxorubicin: 273.28 Da
According to Gemini, "Drugs that cross the BBB generally must be lipophilic (lipid-soluble), have a low molecular weight—typically under 400–600 Da—and have a low polar surface area or few hydrogen bonds. They must avoid active efflux transport systems (like P-glycoprotein) and not be highly bound to plasma proteins." So the requirements for an IV infusion drug are pretty stringent.
However, there is an alternative route and that is, again according to Gemini, "[administration] directly into the brain to bypass the BBB. This approach, known as local or regional drug delivery, is used to treat primary brain tumors (like glioblastoma) or brain metastases, allowing high concentrations of medication to reach the tumor without causing systemic toxicity." I should think that the advantage of using pre|CISION for this is that, whilst the pre|CISION drug itself would be too big to cross OUT of the brain, the warhead, its metabolites and the leaving group from the pre|CISION substrate could all be below the size needed to cross out of the brain. Anyway, CC wouldn't have specifically mentioned brain cancer if it weren't a possibility.
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