Six years ago a trio of Car-T therapy companies debuted on Nasdaq at valuations of $500m to $2bn, and two of them, Kite and Juno, were later sold for a combined $21bn. But the third, Bellicum, has lurched from one disaster to another, seeing 97% of its value wiped out.
Yesterday the axe fell, with the announcement of the loss of 79% of Bellicum’s jobs, a deeply dilutive financing, and a narrowed project focus. Remarkably, however, one of the projects Bellicum is to focus on, BPX-601, has just shown zero activity, casting serious doubt over what remains of the group’s technology. How could things have gone so badly wrong?
It seems obvious, with hindsight, that Bellicum was not ready for prime time, and that the utility of the off (and later on) switches that had been its claim to uniqueness had not been proven. The group now finds itself tinkering with technology in the full glare of the public markets, when this is kind of work is usually done by private start-ups when still in stealth mode.
Bellicum’s latest plan, armed with $25m from the sale of stock that almost doubles its shares in issue, is to focus on BPX-601 and BPX-603, which both use a rimiducid-mediated activation technology.
However, initial BPX-601 data, which Bellicum announced alongside the restructuring, will not prompt much optimism: in four pancreatic cancer patients there were no remissions, and one had a serious episode of cytokine release syndrome to boot. Cytokine release usually correlates with efficacy.
And it gets worse: Bellicum claims to have seen evidence that multiple administrations of rimiducid did activate BPX-601, seeing cytokine levels rise, for instance, but despite this there was no increase in circulating Car-T cells versus a single rimiducid dose.
Such a finding clearly has major implications as to the viability of Bellicum’s switch technology, which is meant to yield controllable Car-T cells that have controllable side effects. Yet Bellicum is now destined to pursue BPX-601, which targets PSCA, and BPX-603, an anti-Her2 Car that has only just cleared US IND to start a clinical trial and carries its own questions.
This is not Bellicum’s first change of tack. The group’s initial promise was that of Car-T cells that could be ablated in the event of serious toxicity, and to be fair this generated interest at a time when some thought that no cell therapy would be approved without such a “safety” switch.
However, Bellicum likely held out for too high a price in deal talks, and other companies either developed their own switch technologies or used an identical approach, suggesting that this had no relevant patent coverage. Ultimately, of course, Car-T therapies were approved with no such off switch.
The group then pivoted to rivo-cel, a stem cell transplant adjunct meant to provide a fast route to market. But that approach collapsed when the standard of care changed, rendering pivotal trials redundant and scuppering rivo-cel along with rival projects from Kiadis and Molmed.
It has now become evident just what a speculative technology play Bellicum was. With hindsight it should probably not have seen the light of the stock markets at such an early stage, and much more validation work should have been done before Bellicum staked its public reputation on clinical trials.
|Bellicum's slow fall from grace|
|23 Dec 2014||IPO raises $160m gross, valuation $600m, focus on Car-T cells with “off” switches|
|11 Mar 2015||Bellicum pitches idea of non-exclusive licences to “off” switch tech; none is signed|
|31 Jan 2017||Rick Fair replaces Tom Farrell as CEO, to focus on rivo-cel|
|30 Jan 2018||Rivo-cel is put on US clinical hold for 4 months|
|20 Apr 2018||$69m gross raised in public offering|
|16 Jul 2018||CFO to leave|
|27 Jun 2019||Confirmatory trial of Molmed’s rival stem cell transplant adjunct fails|
|21 Aug 2019||$70m raised in public and private stock sale|
|17 Oct 2019||EU regulators reject Kiadis’s rival stem cell transplant adjunct|
|5 Feb 2020||1-for-10 reverse stock split|
|21 Jan 2020||Manufacturing, office and lab space sold to MD Anderson for $15m|
|29 Oct 2020||Strategic change of focus, 79% staff cut and $25m dilutive raise|
|Source: company disclosures.|