• Application route: Two routes of cell delivery have been mainly used in cell therapy: intracoronary arteries or intra-myocardial. Intra-myocardial delivery with several injections could be a risk factor for triggering ventricular arrhythmias. On the other hand, intra-coronary cell administration might reduce the risk for arrhythmias but may foster cell loss and decrease LVEF improvement. Indeed, experimental studies have shown that cell retention within the few hours following intra-coronary delivery was consistently lower than following intra-myocardial delivery, even when taking in account mechanical leakage and washout favoured by beating heart.
For CellProthera, intra-myocardial cell delivery is the best route of injection to achieve an optimal cell therapy efficacy on cardiac function. To prevent ventricular arrhythmia and increase CD34+ cells homing in the heart, CellProthera has developed an injection process into the infarcted zone, which reduce arrhythmia risks, and can be performed on an outpatient basis.
• Timing of cell delivery: A huge dilemma remains regarding the best time for stem cell delivery to patients. Many trials suggest that the optimal efficacy of cell therapy is observed if administered early after AMI (between 8 days and 2 months after AMI). However, it might be dangerous to perform direct cell injection into the ischemic lesion before the end of the second week, the injured myocardium being too crumbly within the immediate post-AMI period to be safely injected. On the opposite, if the treatment is administered a long time after AMI, diminution of chemokines secretions and scar formation associated with fibrosis occurrence will progressively reduce the benefit of cell therapy. This lack of efficacy was observed during the Proof of Concept trial performed by Pr. Hénon. One patient treated 8 years after AMI with CellProthera therapy saw no improvement of heart function, and died 5 years after its inclusion in the trial.
Since, the development of scar/fibrosis formation is relatively slow and takes several months to be fully achieved, the optimal timing of cell delivery is comprised between 2 weeks and 6 months after AMI.
• In terms of manufacturing, the Cellprothera project is also innovative because of the chosen model: the CD34+ grafts are not manufactured by CellProthera, but by a large network of GMP Cell Therapy Centers, in a standardised way. This will allow to disseminate much more efficiently the therapeutic offer, and to share investment risks and benefits between the Company and CTCs. This particular model is needed to anticipate the growing demand. We estimate to treat until 16.000 so far by 2032, in targeted regions (Europe, North America). To meet this demand, over such large territories, logistics (blood samples and graft shipping within 37h) will be a critical parameter. Having a large network of CTCs equipped with CellProthera’s technology, at the centre of a local network of nearby hospitals, is the key to solve this issue economically. Besides, Cellprothera aims to request an early access authorization in France in order to sell its therapy in early 2025, waiting for the market authorization in Europe and USA for 2027.
