Caribou’s allogeneic Car meets a six-month bar
But relapses are still frequent – a problem that, curiously, higher dosing has not assuaged.
With allogeneic Car-T projects struggling to yield lasting responses, six-month durability has emerged as something of a minimum for a patient’s remission to hit to be considered real. And yesterday Caribou joined Allogene in claiming that around half of lymphoma subjects treated with its project can develop responses that are maintained to this time point.
The 50% bar is relevant because it broadly matches what autologous Car-T therapies are capable of in this setting, and with the convenience of an off-the-shelf therapy the possible advantages are obvious. However, Caribou’s data, from the latest iteration of the Antler study of CB-010, make it clear that relapses will continue to be watched closely.
For now Caribou appears to have persuaded enough doubters with a dataset that now includes 16 patients, versus six in December. Its announcement was immediately followed by an upsized $125m equity offering, though with this being priced 20% below last night’s close today’s share price drop was unavoidable.
Sentiment has also been boosted by Caribou securing a $25m equity investment last week from Pfizer – a big pharma company that, via Cellectis, had had a significant presence in allogeneic Car-T therapy, only to take a step back five years ago.
CB-010 stands as the lead in Caribou’s pipeline of Crispr-edited allogeneic cell therapies, and yesterday’s update was the fourth from the first-in-human Antler study in relapsed/refractory lymphoma.
At last year’s EHA meeting the first data showed the first six patients given 40 million cells all going into complete response, but three relapsing by six months. In December the focus was still on the same six patients, but only two were by then in CR, with Caribou promising more data this year, including from higher doses of CB-010.
That came yesterday, with the good news that the two responding patients were still in CR, now at 18 and 24 months. Not only that, they have been joined by five other responders beyond six months. In a dataset comprising 16 patients Caribou has thus been able to claim a 50% six-month remission rate, and 44% rate of six-month CRs.
More puzzling is the fact that patients continue relapsing in spite of CB-010 being dosed higher. Four of the five new responders had been given 80 million cells, but in three subjects given 120 million cells there was one non-responder – Caribou’s first – and two remissions lasting less than three months.
CB-010 is continuing to post a promising safety profile, with rates of severe cytokine release, neurotoxicity and infections of zero, 13% and 6% respectively. This appears broadly in line with the latest data Allogene presented on its corresponding CD19-targeting project ALLO-501/501A, at last month’s Asco meeting.
Allogene has also been able to claim having solved, to an extent, its earlier problems with relapses, with a new manufacturing process resulting in 42% of patients having CRs at well beyond six months. However, the Asco data comprised just 12 subjects.
While both datasets are promising, small patient numbers – from both companies – limit their reliability, especially given the bar that autologous Car-T therapy has set. Gilead’s Yescarta, for instance, puts some 50% of lymphoma patients into CR, but the Zuma-1 study has shown about 70% of these remissions maintained at two years.
It will be some time before Caribou or Allogene are able to boast datasets as mature as that.