ASH 2024 | Investigating a novel ADC, HDP-101, for the treatment of relapsed multiple myeloma

Yeah, so this is a new ADC – I presented this first at the IMS meeting – but a new ADC that differs from the previous clinically evaluated ADCs like belantamab mafodotin in respect to the payload because it has as you said the amanitin as a payload which has a completely different mode of action because it does not depend on proliferation of the cells, it shuts down basically transcription of genes in general and so it is very effective also in resting cells for example as we have shown also pre-clinically. 

And the Phase I now is in dose escalation – we have gone up to 100 mcg per kilogram so far and in the highest dose cohort we saw like a 50% response rate and we saw CRs for example in one patient the CR after nine prior lines of therapy including CAR-T cell therapy and bispecific antibodies and an ongoing CR in months, I think, 15 now. 

So of course, dose escalation is ongoing and dose schedule optimization is ongoing. Why? Because we saw in the highest dose cohort, we saw several transient rapid declining, but rapid re-increasing thrombocytopenias. I should phrase it differently – so the thrombocytelevels decreased rapidly after the first infusion but came back to acceptable ranges quite early so the mechanism is not entirely clear, but that led to a different approach in terms of dose scheduling. So from every three week that we split dose for example in two initial doses or we split to a weekly dosing into one which is now ongoing, and so what we see so far it looks like this can mitigate this initial platelet drop so that the dose escalation as of now after the ASH meeting actually is now ongoing with higher doses and let’s see what kind of response rates we will get there. As I said the initial data look very very promising as a single agent in late-line patients with even achieving CR in some patients.

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