A new desk note from Spark Plus analyst Cyprus Sia has provided a comprehensive look at Arovella Therapeutics Ltd (ASX:ALA) and the work the biotech company is doing towards developing invariant natural killer T (iNKT) cell therapies, including its pioneering ‘armoured’ CAR-iNKT product.
“The CAR-T cell therapy market has grown from 0 in 2016 to >US$3.6 billion in 2023 and is expected to exceed US$35 billion by 2032. As a result, M&As and research collaborations from big Pharma in this space are increasing," said Sia.
“Preclinical studies suggest that CARiNKT cells will supersede CAR-T cell therapy due to its superior specificity, antitumor activity and allogenic properties.
"Arovella Therapeutics is one of the only six companies in the world developing a CAR-iNKT cells therapy currently which, we believe, positions it as a potential acquisition target.”
Arovella is currently working on three programs that leverage its iNKT cell therapy platform.
Highlights
Spark Plus outlined the following highlights of Arovella:
Targets to commence Phase 1 clinical trial in 2024
ALA has achieved major manufacturing milestones including the production of a GMP-certified lentivirus and completion of its process development and scale-up for ALA-101, which will now progress to engineering to GMP runs to produce clinical-grade material.
The company intends to commence a Phase 1 clinical trial for CD19+ lymphoma and leukaemia patients in late 2024.
Fully funded to reach Phase 1 clinical trial for ALA-101 and capture data
ALA raised A$12.5 million in March 2024 to end the quarter with circa A$15.1 million which the company expects will be sufficient to fund its activities over the next 12 months.
These activities include commencing a Phase 1 clinical trial in non-Hodgkin’s lymphoma and leukaemia using ALA-101 and obtaining preliminary data.
Strong pre-clinical data
A lymphoma mouse model (n=64) showed mice treated with ALA-101 (n=19) have a 50% higher survival rate as compared to the current gold standard, CAR19-T cells (n=19).
In addition, mice treated with ALA-101 were able to eradicate tumour cells a second time through a spontaneous secondary remission (n=4) without additional dosing.
Allogenic CAR-iNKT cells may improve access
iNKT cells do not cause graft versus host disease (GvHD) so they can be isolated from a healthy donor, engineered to produce a CAR, frozen and stored, thawed and infused into a patient on demand.
This can radically shorten the time to treatment which, for aggressive cancers, may be the difference between life or death.
Expanding pipeline
ALA has licensed two additional technologies, with well-established preclinical data, to integrate into its iNKT cell platform.
- CLDN18.2 targeting monoclonal antibody, which can be used to create a CAR, unlocking the ability to target gastric cancers, gastroesophageal junction cancers and pancreatic cancers markets valued at an aggregated US$6.2 billion.
- IL-12-TM, a modified version of the human cytokine, interleukin 12, that enhances CAR-iNKT cell persistence, cell number, and anti-tumour activity.
By the end of 2024, ALA will attempt to produce CLDN18.2- iNKT cells, integrate IL-12-TM into its solid tumour programs, and validate their activities in preclinical studies.
M&A and investments into CAR technology
M&A and investments into CAR technology by big Pharma averaged US$382 million over the past three years. Most of these deals are done during early-stage development (preclinical, Phase 1, or Phase 1b) alluding to a proxy valuation for ALA.
Most deals are in the CAR-T cell space due to the lack of CAR-iNKT cell programs under development. We do not rule out the possibility of ALA becoming an acquisition target or entering a development collaboration with a big pharma partner, especially so if the Phase 1 results are positive.