Alligator Bioscience’s CD40 agonist mitazalimab has recently shown promising results in a second interim analysis of the OPTIMIZE-1 phase II study in pancreatic cancer. The results will be presented by CSO Peter Ellmark at the 3rd Annual Tumour Myeloid-Directed Therapies Summit in Boston. His presentation also features the company’s bispecific CD40/CEACAM5 antibody ATOR-4066 and its potential to induce strong anti-tumour response in patients with CEACAM5-expressing tumours. BioStock contacted Peter Ellmark to get to know more.
Alligator Bioscience is a clinical-stage biotechnology company developing tumour-directed immuno-oncology antibody drugs. The company’s lead asset mitazalimab is a CD40 agonist that binds to the CD40 receptor on dendritic cells, resulting in activation of the immune system’s tumour specific T cells that selectively attack the cancer.
Phase II study OPTIMIZE-1
The safety and efficacy of mitazalimab is currently being evaluated in a phase II study, OPTIMIZE-1, in previously untreated patients with metastatic pancreatic ductal adenocarcinoma. In the study, mitazalimab is given in combination with the first-line chemotherapy treatment mFOLFIRINIOX.
Additional positive interim data
On January 2, 2023, Alligator announced positive interim results from the OPTIMIZE-1 study showing an Objective Response Rate (ORR) of 52 per cent in an initial cohort of 23 patients. About six months later, on June 26, Alligator announced additional positive interim data based on the full cohort in the study. The analysis showed an increase in the ORR to 57 per cent in the initial 23 patients, suggesting a durable benefit for patients, as well as an ORR of 44 per cent in the full cohort of 57 patients.
The latest analysis also shows an interim median Duration of Response (DoR) of 8.7 months, which is likely to evolve over time and compares already favourably with the 5,9 months reported with FOLFIRINOX in a similar patient population.
The interim data confirms the potential of mitazalimab as a therapeutic option for first line pancreatic cancer patients. Read more about the interim data in BioStock’s interview with CMO Sumeet Ambarkhane.
Presentation at Tumour Myeloid-Directed Therapies Summit
The results will soon be presented at the 3rd Annual Tumor Myeloid Directed Therapies Summit on July 18-20 in Boston. Peter Ellmark, CSO of Alligator Bioscience, is one of the expert speakers at the conference and he will also be co-hosting the Industry Leaders’ Fireside Chat: “Reviewing the Current Landscape & Future Potential of the Myeloid”.
Peter Ellmark’s presentation will also feature preclinical data on ATOR-4066, the company’s 3rd generation bispecific antibody targeting CD40 and CEACAM5. ATOR-4066 was developed using the company’s proprietary technology platform Neo-X-Prime and is intended for the treatment of solid metastatic tumours.
Interview with CSO Peter Ellmark
BioStock contacted Peter Ellmark to get to know about the potential of Alligator Bioscience’s CD40 portfolio.
First of all, why is targeting CD40 useful in cancer immunotherapy?
– Targeting CD40, and thereby activating myeloid cells, provides an opportunity to effectively address one of the major challenges in the field of immune-oncology today, which is to treat cancers with an immune suppressive microenvironment. Pancreatic cancer is one such indication, but there are many other indications where CD40 agonists may be the key to increase response rates and duration of response.
– There has been a growing interest in myeloid targeting therapies in the last few years due to their central role in the immune system and CD40 stimulation stands out as a unique pathway to turn a suppressive tumour microenvironment into a tumouricidal one.
»There has been a growing interest in myeloid targeting therapies in the last few years due to their central role in the immune system and CD40 stimulation stands out as a unique pathway to turn a suppressive tumour microenvironment into a tumoricidal one«
Your upcoming presentation will not only highlight the new interim data for mitazalimab, but also the potential of the bispecific antibody ATOR-4066. Why is ATOR-4066 a valuable part of Alligator’s CD40 portfolio?
– ATOR-4066 is a 3rd-generation CD40 agonist that we have designed based on our long-standing expertise in CD40. It was developed using our proprietary Neo-X-Prime platform that generates bispecific tumour-antigen conditional antibody agonists able to significantly boost anti-tumour activity by efficiently connecting dendritic cells to tumour debris.
– Very importantly, ATOR-4066 activates CD40 only in the presence of CEACAM5, which is preferentially expressed on certain tumour types. This is expected to make this antibody extremely potent and specific with a very favourable safety profile. The preclinical data that I will present at Tumour Myeloid-Directed Therapies Summit highlights the potential to further improve anti-tumour activity by targeting CD40 and the tumour antigen CEACAM5 simultaneously. The Neo-X-Prime platform is very well positioned compared to other tumour targeting therapies in development and provides excellent patient stratification opportunities that makes ATOR-4066 well-placed to make a significant impact in the immuno-oncology space in the near future.
»Very importantly, ATOR-4066 activates CD40 only in the presence of CEACAM5, which is preferentially expressed on certain tumour types. This is expected to make this antibody extremely potent and specific with a very favourable safety profile.«
What are the next steps in the development of mitazalimab and ATOR-4066?
– For mitazalimab, the next key milestone is to report topline data from OPTIMIZE-1 in early Q1 2024, providing mature ORR data, progression free survival, overall survival and duration of response data. In addition, we are engaging in discussions with regulators on the best path to market in metastatic pancreatic cancer and intensifying our business development efforts to find the right partner who can bring mitazalimab to patients as fast as possible. For ATOR-4066, we are working to strengthen the translational data package supporting the upcoming clinical development.
The content of BioStock’s news and analyses is independent but the work of BioStock is to a certain degree financed by life science companies. The above article concerns a company from which BioStock has received financing.
»For mitazalimab, the next key milestone is to report topline data from OPTIMIZE-1 in early Q1 2024«