It’s a good job that Kiadis has a plan B to which it can now pivot. The highly predictable rejection of the EU filing for its stem cell transplant adjunct ATIR101, expected imminently, mirrors the problems Molmed had endured with its rival procedure, Zalmoxis, culminating in the withdrawal of its own EU approval.
Kiadis has put the blame squarely on the fact that the standard of care in post-transplant patients has changed to include the so-called Baltimore protocol – a regimen that was not part of its supportive trial. This makes near-term EU approval for Bellicum, the third player in this space, look impossible.
The reason is that BP-004, the study Bellicum had run to support conditional EU approval of its BPX-501 procedure, does not include the Baltimore regimen either. Baltimore is now the standard of care for patients who lack a fully matched donor, and involves administering the chemotherapy cyclophosphamide after transplantation to reduce alloreactivity.
Crucially, Bellicum says it expects to file BPX-501 with EU regulators in late 2019/early 2020, if it can secure a partner. Based on Kiadis’s experience it now seems highly unlikely that a partner would be willing to come forward on the strength of supportive data that do not include the Baltimore regimen.
|Stem cell transplant add-ons|
|Zalmoxis||Molmed||Ganciclovir/valganciclovir-triggered "suicide switch"||Conditional EU approval withdrawn|
|ATIR101||Kiadis||GvHD-causing cells removed using Kiadis's photodepletion tech||Conditional EU filing rejection imminent|
|BPX-501||Bellicum||Rimiducid-triggered "suicide switch"; alpha/beta T cells removed||EU filing in 2019/20 depends on finding partner|
|Source: Company websites.|
For Kiadis yesterday’s revelation, that an EU rejection of its conditional ATIR101 filing is imminent, brings to a close two years of agony. ATIR101 had been filed back in 2017 on the back of a phase II comparison against historical data. CHMP questions set this back by six months, and in June Kiadis put back its EU launch expectations to 2020.
The project, like Zalmoxis and BPX-501, is a procedure allowing stem cell transplant to take place when only a half-matched, rather than fully matched, donor is available. Attention now turns to the Kiadis’s phase III study, Hatcy, which does compare ATIR101 against the Baltimore regimen, but which does not read out until 2021.
Bellicum, too, has an ongoing phase III study, Thrive, that compares BPX-501 against the Baltimore protocol, though its primary endpoint differs versus Hatcy. Most importantly, Thrive does not read out for another four years, kicking Bellicum’s can down the road to a point where BPX-501 becomes a negligible part of its investment case.
Jefferies analysts today wrote that conditional EU approval for ATIR101 had been a key part of their Kiadis thesis, though they expected limited commercial revenues. This damning view likely reflects the dismal performance of Molmed’s Zalmoxis in its brief time on the EU market, and casts doubts over the economic viability of any product targeting this space – even if it managed to secure approval.
Earlier this year Kiadis bought the private NK cell therapy player Cytosen, to which it can now pivot, though perhaps not without a fresh cash injection. Unlikely as pulling off a fund-raising might now seem, this is precisely the trick that Bellicum, capitalised at a mere $40m, managed in August.
|Phase II trial||CR-AIR-007 (NCT01794299)||BP-004 (NCT02065869)|
|Primary endpoint||Transplant-related mortality (single cohort)||Event-free survival (single cohort)|
|Result||13% at 6mth||91% at 6mth|
|Phase III trial||Hatcy (NCT02999854)||Thrive (NCT03699475)|
|Primary endpoint||GvHD-free, relapse-free survival vs Baltimore regimen||Overall survival vs Baltimore regimen|
|Result||Completes Feb 2021||Completes Dec 2023|