Jacob Plieth doet ook een duit in het zakje:
Ash 2022 – Affimed feels the pain
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Jacob Plieth
Affimed investors find that what goes up must come down, though the stock owes only part of its fall to an Ash presentation.
Affimed was one of the early winners of the Ash abstract drop last month, but today it felt the pain. As the markets opened on the first trading day of the haematology conference the shares were off 38%, while other Ash-relevant stocks like Adicet, Fate, Kura, Caribou and Allogene were nursing losses of 37%, 15%, 14%, 11% and 11% respectively.
With a few important caveats, however, the dataset Affimed had touted going into Ash – an MD Anderson-sponsored study of AFM13 combined with NK cells – more or less held up. It was results of a separate Affimed-sponsored study of AFM13 monotherapy, press released and not presented at the conference, that might have been more responsible for investors fleeing.
The study, Redirect, was testing AFM13, an NK cell-redirecting anti-CD30 MAb, in CD30-positive peripheral T-cell lymphoma (PTCL). On Saturday Affimed press released a respectable 32% overall response rate from 108 efficacy-evaluable patients.
But poor persistence was a setback. Median duration of response was 2.3 months, below the 8.4 months and 9.4 months seen with Beleodaq and Folotyn in separate trials, though median PFS of 3.5 months and OS of 13.8 months were more in line with those established drugs.
Wells Fargo analysts called the survival data confounding, and removed AFM13 monotherapy in PTCL from their models because the duration of response came up short of their internal target of 8-9 months. Affimed itself said it would now focus on combining AFM13 with AB-101 NK cells, which it recently secured via a deal with Artiva Biotherapeutics.
No surprise
In reality none of this should have come as a surprise. AFM13 has long been seen as mediocre in monotherapy, and it was only the early results of MD Anderson’s trial combining it with NK cells that revealed the approach’s promise.
The basis for this is that many lymphoma patients are said to lack sufficiently potent NK cells of their own; give them a fresh source of NK cells and you solve this problem. This view drove Affimed’s Artiva deal, and the updated results of the MD Anderson trial, in CD30-positive lymphoma, have now informed Affimed’s strategy in PTCL.
Those MD Anderson data featured at Ash on Saturday, and comprised 41 patients, all of whom were refractory to or intolerant of Seagen’s Adcetris. Initial responses across all doses were 93% overall, with a 66% rate of complete remissions.
However, here too AFM13 faces durability questions. The data were split into 19 patients who had received two cycles of therapy, and 22 who had received up to four cycles, and only four of the 10 complete responders seen in the former group were still in remission at 12 months – two having received stem cell transplants.
Meanwhile, most of the remissions seen in the second group are ongoing, but are of short duration. “When we go up to four cycles we’re hoping that duration of responses will increase,” said the presenting investigator, Dr Yago Nieto.
He also revealed that two deaths had occurred in the study, one due to Covid and the other to stroke. Despite cell therapies’ documented links with susceptibility to infections and brain haemorrhage, these two grade 5 events were deemed unrelated to treatment, said Dr Nieto.
If durability remains unproven, so does the efficacy Affimed might see in a future company-sponsored trial. It is assumed that when Affimed co-administers AFM13 with Artiva’s AB-101 cells the finished product will behave at least as well as the co-complexed AFM13/NK cells used by MD Anderson, but this has yet to be shown clinically.
And Affimed’s own combo study is still some way off: the company has yet to hear back from the FDA, but expects to file an IND in the first half of next year to start a registrational trial of AFM13 plus AB-101 in Hodgkin lymphoma and CD30-positive PTCL.