Why A Cell Therapy CEO Waited Until Phase III To Outsource
By Louis Garguilo, Chief Editor, Outsourced Pharma
Sometimes, you have to go it alone. For a while, at least.
The mantra across biotech has long been clear: engage your CDMO early, and let those experts guide you into manufacturing.
Matthieu de Kalbermatten, CEO of CellProthera, a regenerative cell-therapy developer specializing in cardiovascular diseases, begs to differ.
His view is forged less on an iconoclystic streak, and more on a development strategy born of necessity.
Necessity because in 2009 when CellProthera started up (in Mulhouse, France) there was no outside expertise to be found.
De Kalbermatten is particularly proud of the “GMP-compliant” adjective in that inclusive statement. Going it alone at first, he says, has been greatly beneficial.
It wasn’t until its post AMI cell therapy enters Phase 3 trial that CellProthera has gone down the CDMO partnering path.
AMI is short for acute myocardial infarction – better know as a heart attack. According to CellProthera, every year in France 80,000 people suffer a heart attack; approximately 12,000 of whom will die. CellProthera’s lead therapy is ProtheraCytes, an autologous therapy registered as an Advanced Therapy Medicinal Product (ATMP) by the European Medicines Agency (EMA).
In May 2025, CellProthera announced it had selected a manufacturing partner, CELLforCURE by SEQENS.
You can bet it was a rigourous selection process, and we’ll get into that.
Our first focus, though, is learning from that initial success CellProthera found staying internal as a development organization.
The Advantage Of Staying Internal
“When we started, there was almost no CDMOs approved to produce cell and gene therapy at all,” De Kalbermatten explains. In France where his initial target-population resided, “there was nobody to produce clinical grade cell-therapy for our needs.”
Many developers might have changed course to a more “realistic therapy-development pathway” at that point.
However, says De Kalbeermatten, “You simply have to decide to do it yourself to proceed.”
That requires gaining the confidence, understanding, commitment, and funding to build facilities at least adequate enough to produce regulatory-acceptable materials, and create processes to see you through your first phases of the clinic.
Fortunately, in most cases for CGT that “build out” is comparatively minor in scope, and expenditure. Building up the internal knowhow and following regulatory evolutions might be the more difficult task.
Looking back, De Kalbermatten is categorically pleased with how things have turned out. CellProthera built a pharmaceutical-like (pharma-lite?) establishment, but with a “complete quality management system, which is the ultimate need.”
“We developed our own QC methods and put the responsibility of releasing the batch in our own hands, not an external partner,” he explains. He advises as much for other biotechs (of any shape or size).
“Often," he admits, "startups don’t have a GMP-compliant quality management system in place. They prefer to subcontract to the CDMO.”
However, he says, “we have learned so much. We are on top of our process and each component of it. We are not depending on a CDMO that has many customers, and may have a different agenda and timelines.”
That “different agenda,” he makes clear, is not malicious; it’s structural – a CDMO fulfilling its business model. Nonetheless, it also means you might have to ask each time, ‘Can you validate this method? Can you change this parameter? How much more will it cost?’”
“Flexibility costs money,” De Kalbermatten says. “Change control costs money. In autologous cell therapy, where starting material differs from patient to patient, this becomes acute.”
Dual (In)Dependency
As it turned out, CellProthera needed plenty of flexibility – and it was afforded by its internal capabilities.
Their therapy process was developed using healthy donors. Phase 2 then began treating older cardiac patients. “Suddenly your process doesn’t work anymore. It used to be healthy 20-years-olds; now you don’t have those same raw materials.”
“We did all this change control during Phase 2 ourselves,” De Kalbermatten explains, “because we had the internal capability. We had to do some serious modification and optimization of the process to make it work for those patients.”
De Kalbermatten believes had they been dependent on a CDMO, the process could not have been improved as optimally or as cost efficiently.
But back to funding all this, a decade earlier when CellProthera pitched its homegrown automation and equipment strategy to investors, their attitude was dismissive.
“What the heck are you talking about?” was a typical reaction, says De Kalbermatten.
“You have to focus on your preclinical and then clinical development. Why are you talking now about developing equipment, devices and machines for automated production?”
Today has brought on a sea change. “Now everybody’s saying, ‘Oh my God, you’ve started to develop something. Think about the manufacturing while it isn’t too late.’
“And the next piece of advice? Find a CDMO.”
De Kalbermatten understands that prodding. "One thing I would say to the new entrepreneur, though, is do not abandon your convictions too quickly, even if they are not in line with the general thinking of the moment.”
“Why outsource so early?” he asks rhetorically. Your product is your process, as we say in CGT development circles. It’s your value proposition, your intellectual properties, “It is everything.”
De Kalbermatten is equally candid about the CDMO buildout in cell and gene.
“A few years ago, small CDMOs started popping up trying to do what we’ve done. But autologous manufacturing is lumpy. Capacity planning is complex. Idle cleanrooms are expensive. Now we have overcapacity.”
Which twists our narrative like a pretzel.
When CellProthera started out, there were few CDMOs to take on its work. Now there may be too much capacity.
In either market situation, De Kalbermatten advises we consider his experience.
While every biotech has its differences, try to keep your beginning science and developing processes internal; later bring in CDMOs that can escalate you into clinical trials and push you past the commercialization goal line.
De Kalbermatten and team have now selected their external partner to accomplish that. In part two, we’ll lean into that selection process, and more on cell and gene therapy outsouring.