Alligator’s mitazalimab data published in The Lancet Oncology
Alligator Bioscience’s phase II data with cancer immunotherapy mitazalimab have been published in The Lancet Oncology – one of the most prestigious and internationally trusted scientific journals in the world. BioStock spoke with Alligator’s CEO Søren Bregenholt to get his reaction.
Alligator Bioscience achieved a significant milestone earlier this year when it met the primary endpoint in its OPTIMIZE-1 phase II trial. The purpose of the study was to evaluate CD40 agonist mitazalimab in combination with mFOLFIRINOX, the most effective chemotherapy regimen for pancreatic cancer.
Alligator reaches proof-of-concept with mitazalimab
The trial’s results revealed a confirmed objective response rate (ORR) of 40 per cent and unconfirmed ORR of 51 per cent, indicating a substantial clinical benefit. Additionally, the study reported a median duration of response (DoR) of 12.5 months, progression-free survival (PFS) of 7.7 months, a disease control rate (DCR) of 79 per cent in 57 evaluable patients and overall survival (OS) of 14.3 months.
Dr Zev Wainberg, co-director of the UCLA GI Oncology programme and clinical consultant for the mitazalimab clinical development programme, highlighted the significance of the DoR in the OPTIMIZE-1 study, noting that it exceeds previously reported durations for metastatic pancreatic cancer. This prolonged response is expected to translate into better overall survival, with ongoing data suggesting even longer durations as the study progresses.
Major publication for Alligator
Alligator continues to attract substantial interest from the scientific community. This was evident during the latest ASCO meeting in Chicago, where the company has presented two clinical abstracts on its lead candidate.
The interest was amplified exponentially after the OPTIMIZE-1 data was published in The Lancet Oncology. The journal has an impact factor of 51.1, making it “the world-leading clinical oncology research journal globally,” according to Clarivate’s Journal Citation Reports.
Alligator’s CEO Søren Bregenholt is in attendance at the ASCO conference, and according to him, the publication is generating quite the buzz.
– Presenting our clinical data at such a prestigious event like ASCO, and then publishing in a world-leading and peer-reviewed journal, is a significant milestone for Alligator Bioscience. There was substantial interest in our presentations at ASCO, and this impression was further reinforced by the strong feedback received in response to The Lancet Oncology article. It enhances our profile with these important audiences and is a validation of both the robustness of our research and the exciting potential of mitazalimab, on which we are expecting follow-up data from the OPTIMIZE-1 trial in late June.
The publication will give Alligator a significant boost as the company seeks a commercial partnership to advance mitazalimab through its final stages of clinical development, with a pivotal registration study slated to begin in the first half of 2025.
Start of new phase I trial with mitazalimab
As Alligator Bioscience continues to advance its clinical programme, the interest in mitazalimab is showing no signs of slowing down. Alligator has been approached by several clinical sites interested in conducting investigator initiated trials. One example of that is a phase Ia/b single-centre clinical study of intratumoral mitazalimab in locally advanced pancreatic cancer (LAPC), which was initiated in May. The study, funded by the National Cancer Institute and conducted by Moores Cancer Center at University of California San Diego, is aimed at evaluating the safety and efficacy of mitazalimab at the time of surgical irreversible electroporation (IRE).
This technique uses short, intense electrical pulses to destroy cancer cells. It targets these cells precisely without harming surrounding tissues, making it a good option for treating tumours near vital structures. According to Rebekah White, MD, principal investigator of the study, preclinical data suggest that the combination of IRE with CD40 agonism can generate systemic anti-tumour effects.
CEO insights
BioStock reached out to CEO Søren Bregenholt to get his take on the latest achievements for the company.
Søren, how significant is this latest publication?
– It is very important, and we are naturally proud, to have this validation from the scientific community of the highly promising results of the OPTIMIZE-1 mitazalimab study – both from The Lancet Oncology and also our presentations at ASCO. A substantial number of patients were either on treatment or in the follow-up at the time of the primary analysis. Consequently, the 18-month survival follow-up data, which we expect at the end of June 2024, should provide further important insights into the potential of mitazalimab.
How will this impact your push towards phase III and ongoing partnering efforts?
– We are currently conducting due diligence and negotiations aimed at finding the best partner to take mitazalimab through Phase 3, regulatory approval and commercialisation. This strong validation of, and publicity around, the data of course help to maintain the profile of mitazalimab, and Alligator Bioscience, with potential partners. It is also a good reminder of the approaching follow-up data.
Do you anticipate that the publication will have an impact on Alligator’s standing and credibility in the field of oncology, including investors?
– Firstly, I would say that our track record, and the initial data release in January 2024, already provide us with a strong reputation as an innovative biotech company developing tumour-directed immunotherapies with the potential to significantly improve treatment options for cancer patients. We regularly receive strong feedback from both investors and scientists on the work we are doing, and the publication in The Lancet Oncology will further reinforce that.
Regarding the new phase I trial, why is IRE the basis for this phase I study with mitazalimab?
– Simplistically, the IRE procedure directs a localised high voltage current trough the pancreatic tumour, which kills the tumours cells. It is used for a number of solid tumours, and Dr. Whites lab is pioneering its use in pancreatic cancer. In this trial she will test whether co-treatment with mitazalimab will activate the immune system to eradicate any residual tumour cells, which could potentially translate into a long-term survival benefit. As IRE is a localised surgical procedure, mitazalimab is administered intratumourally. This will impact mitazalimab’s function, but limit systemic exposure and hence minimise potential side effects.
– The current study is exploratory in nature, and good results may establish a basis for eventually developing mitazalimab in combination with IRE and other surgical procedures, in adjuvant or neo-adjuvant settings.
Could you speak to how you use investigator initiated trials in the development of mitazalimab?
– Absolutely, this is a brilliant point. Since we published the first mitazalimab data from the phase 2 study we have received dozens of study proposals from renown clinical investigators around the world. These suggestion include novel studies within pancreatic cancer, but the majority is in other indications like colorectal, renal, biliary tract, lung cancer and other.
– To me this reflects the uniqueness of mitazalimab’s mechanism, as well as it’s efficacy and safety profile. We are carefully assessing each of these opportunities, with each representing a unique way to explore novel development opportunities for mitazalimab in collaboration with the world’s leading clinical investigators, and expand the number of patients that will eventually benefit from mitazalimab.
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