Is the hype around CAR T-cell therapies real? A recent licensing agreement struck between Legend Biotech and Novartis to advance novel CAR T candidates suggests it might be. The deal raises commercial hopes for other players in the space, including Swedish biotech Elicera Therapeutics. We asked CEO Jamal El-Mosleh whether Elicera could be bound for a similar deal.
Chimeric antigen receptor (CAR) T-cell therapies have shown transformational potential for the treatment of liquid tumours, generating excitement among researchers and oncologists. However, few breakthroughs have been made with this technology in solid tumours due to the harsh microenvironment presented by such tumours and due to the difficulty in identifying an antigen target for the CAR T-cells that is expressed on all tumour cells.
These therapies work by genetically modifying T-cells extracted from a patient’s blood. The modification enables the expression of the CAR molecule, which is designed to recognise and bind to the specific antigen targets on cancer cells found inside the patient. The redesigned T-cells are then infused back into the patient’s bloodstream, where they can actively seek out and kill cancer cells carrying those antigen targets.
Six CAR T drugs have been approved by the FDA since 2017, and all target liquid tumours.
Read more about the promise of CAR T therapies here.
Licensing shines light on the potential to treat solid tumours with CAR T
The excitement is being reflected in the dealmaking world. Earlier this month, a subsidiary of Legend Biotech announced a global licensing agreement with Novartis to advance its preclinical autologous CAR T candidate, LB2102, and other potential CAR T-cell therapies targeting Delta-like ligand protein 3 (DLL3) for development. Meanwhile, Novartis will provide its next-generation T-Charge CAR T-cell therapy platform, meant to streamline CAR T-cell manufacturing, giving greater proliferative potential. This would be the first application of T-Charge to a cell therapy candidate targeting solid tumours.
Under the terms of the agreement, Legend Biotech will receive a USD 100 million upfront payment and will be eligible to receive up to USD 1.01 billion in clinical, regulatory and commercial milestone payments and tiered royalties.
Elicera Therapeutics and its innovative CAR platform
In Sweden, the only biotech also betting on CAR T-cell therapies for the treatment of both liquid and solid tumours is Elicera Therapeutics. The company’s lead candidate ELC-301 is being developed in the clinic for the treatment of B-cell lymphoma, while ELC-401 is in preclinical development for the treatment of glioblastoma, a solid tumour of the brain.
The company can circumvent the challenges brought on by solid tumours with its proprietary genetic engineering platform, iTANK (immunotherapies Activated with NAP for efficient Killing). iTANK arms CAR T-cells with the bacterial protein NAP (neutrophil-activating protein). When introduced into the body, the CAR T-cells bind to their tumour target, activating a signalling process that ultimately leads to the release of NAP around the cancer cells.
This leads to the recruitment of other immune cells in the tumour tissue, thus optimising the CAR T effect. A long-term immunological memory against tumour targets is generated, which prevents relapse in cancer.
Read more about iTANK’s potential here.
BioStock got in touch with Elicera’s CEO Jamal El-Mosleh to get a better idea of how ELC-401 compares to Legend’s LB2102, and whether Big Pharma is paying close enough attention to Elicera.
Jamal, in your eyes, how significant is the Legend Biotech/Novartis deal?
– It’s a very significant deal looking at the early development stage of the asset that was licensed and the large upfront payment and potential milestone payments that it generated. Its also exciting to see that the licensed CAR T-cell therapy will utilise Novartis new T-Charge platform for producing the CAR T-cells.
According to Legend, “LB2102 has an innovative CAR design and armour mechanism that increases its anti-tumour activity.” Would you say the same about Elicera’s CAR design?
– Yes I would, however not knowing the details of the arming technology that is used in LB2102. ELC-401 also targets a solid tumour indication, glioblastoma, and can also likely be applied for treatment of other solid tumours expressing the same target, in our case IL13Ra2. Furthermore, the iTANK-platform can also be used to increase anti-tumour activity (by inducing bystander immunity) but can at the same time also counteract the immunosuppressive tumour microenvironment and strengthen the function of CAR T-cells, something I’m not sure if the arming tech used in LB2102 can do.
How does Elicera’s design differ from Legend’s?
– ELC-401 and LB2102 are developed against two different solid tumour targets, namely IL13Ra2 and DDL3 respectively. In addition, LB2102 uses an, from what I can see, undisclosed arming technology to increase anti-tumour activity. I don’t exactly know what the definition of anti-tumour activity is in their case but for iTANK that means that we can trigger a potent parallel/bystander immune response to activate the patients’ own endogenous T-cells against multiple targets on the tumour, not just against the CAR T target. Furthermore, as stated above, iTANK can counteract the immunosuppressive tumour microenvironment and strengthen function of CAR T-cells.
In the deal, Novartis would use its T-Charge technology for T-cell manufacturing. Is this something Elicera could benefit from as well?
– Hard to say. We received a Vinnova grant last year of 5 MSEK to establish an automated production process and we expect to be able to deliver CAR T-cells to patients “vein-to-vein” in 17 days which I think is about the same for Novartis’ T-Charge platform. In creating personalised CAR T-cell therapies, T-cells first have to be harvested from patients, genetically modified and the expanded ex-vivo before being re-infused into the patients. What the T-Charge platform apparently can do is to provide a way to have most of the expansion being done in-vivo, after re-infusion, which saves time and limits T-cell exhaustion. In comparison, iTANK triggers a bystander immune response that also leads to in-vivo expansion and less T-cell exhaustion. I would however guess that iTANK and T-Charge can be used simultaneously for perhaps even better outcomes.
Finally, can we expect a similar deal for Elicera?
– Our business model is focused on exclusive licensing deals for our drug development programmes and non-exclusive licensing deals for the iTANK-platform. As for our CAR T-cell drug development programmes, we have one, ELC-301, against B-cell lymphoma that is about to enter clinical studies next year, and one, ELC-401, against glioblastoma and other solid tumours that is in preclinical phase. Our ambition is to license ELC-301 after the completion of the upcoming phase I/IIa study while we are open to license ELC-401 in preclinical stage. The recent Legend-Novartis deal showcases the level of interest and value the industry places on these types of therapies in solid tumours. Similarly, earlier this year, a deal between Cellular Biomedicine Group and Janssen showcased the level of interest and value the industry places in CAR T-cell therapies that have delivered strong early clinical data in B-cell lymphoma. Janssen paid USD 245 million upfront for two CAR T therapies, targeting CD20 and CD19 + CD20, after completion of two clinical phase I/II studies.
– My take on these licensing deals are the following: we are in the right place, doing the right things but whether we will be able to deliver the same types of licensing deals for our different CAR T programmes remains to be seen.