Home Interviews “Unprecedented” phase II data for Alligator in pancreatic cancer

“Unprecedented” phase II data for Alligator in pancreatic cancer

Alligator Fas II-data

“Unprecedented” phase II data for Alligator in pancreatic cancer

3 July, 2024

Alligator Bioscience continues to post convincing phase II data with cancer immunotherapy mitazalimab in pancreatic cancer, providing further evidence of the candidate’s potential. Adding to the positive momentum, the Swedish biotech has announced a financing round of up to SEK 80 million extending its cash runway to Q1 2025. This is setting the company up in a position  of strength for their ongoing partnering discussions. BioStock reached out to Alligator’s CEO Søren Bregenholt for a comment on the company’s hot streak.

In January, Alligator Bioscience released top-line data from the OPTIMIZE-1 phase II trial evaluating mitazalimab as a first-line treatment in combination with standard of care chemotherapy FOLFIRINOX. The data showed a confirmed objective response rate (ORR) of 40 per cent, thus meeting the primary endpoint set for this study and also provided strong survival benefit over FOLFIRINOX alone.

Alligator’s CEO Søren Bregenholt stopped by the BioStock Studio to showcase the importance of this data and what it would mean for mitazalimab going forward.

– We’ve had a dialogue with the FDA, and they did not request a phase IIb trial but confirmed that OPTIMIZE-1 is phase III-enabling meaning that we can now proceed with the phase III expected to start in H1 2025. So, we will focus very much on that and discuss with potential partners willing to undertake this important step.

Mitazalimab data is receiving “substantial interest”

The data caught the eye of the scientific and medical community as substantiated in the recent publication 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.

News of the publication came as Alligator presented two clinical abstracts on its lead candidate at the ASCO 2024 annual meeting earlier in June. According to Bregenholt, who was in attendance, Alligator received “substantial interest” and “strong feedback’’ at the conference. Read more here.

The Alligator remains on the prowl during summer

Since the Lancet publication, Alligator has continued on its positive roll, presenting further positive phase II data from OPTIMIZE-1; releasing its 18-month follow up analysis of the trial. Median Overall Survival (OS) increased to 14.9 months – up from 14.3 back in January – and survival rate at 18 months was 36.2 per cent, nearly twice as high as the 18.6 per cent previously reported for FOLFIRINOX alone.

Professor Jean-Luc van Laethem, Head of the Digestive Oncology Clinic in the Gastroenterology Department of Erasmus Hospital (ULB) Brussels and Principal Investigator of the OPTIMIZE-1 trial, also commented on the analysis:

– These results clearly represent a remarkable outcome in pancreatic cancer, with the robust DoR indicating highly consistent clinical benefit resulting in prolonged OS.

Just last week, the data was presented by Prof. Teresa Macarulla Mercade, MD, PhD, Vall d’Hebron, Barcelona, in an oral session at the European Society for Medical Oncology Gastrointestinal Cancers Congress 2024 (ESMO GI 2024) in Munich, Germany, and it’s clinical relevance was subsequently discussed by Dr. Zev Wainberg (UCLA). The presentation outlined the substantial survival benefit observed with mitazalimab as well as its manageable safety profile and unprecedented Duration of Response (DoR).
Alligator’s CMO Sumeet Ambarkhane has previously talked to BioStock in depth about the importance of the DoR value for this study. Read the interview here.

CEO insights

As alluded to in BioStock’s previous conversations with Bregenholt, Alligator is now focused on phase III preparations, including finding a partner to undertake the trial with mitazalimab. Financially speaking, the company can breathe easy, as it recently announced financing of up to SEK 80 million, extending its cash runway to Q1 2025. The financing will be procured through a small issue of convertibles plus a larger straight loan facility agreement with Fenja Capital II, minimizing the potential dilution for investors.

To learn more about this new phase II data set, as well the implications of the new financing round, BioStock turned to Alligator’s CEO Søren Bregenholt.

Søren, this 18-month follow up includes a lot of values and percentages. Can you help us navigate the numbers and what stands out?

Søren Bregenholt, CEO Alligator Bioscience
Søren Bregenholt, CEO Alligator Bioscience

– Yes, these press releases can sometime be a bit heavy on information. The most important new data is the doubling in 18 months survival rate compared to what is currently the standard of care. This means that around 36 patients out of 100 patients that recieves mitazalimab plus chemotherapy were alive 18 months after start of treatment. The corresponding number for chemotherapy alone is 18 out of 100. Hence your probility of being alive at that timepoint doubles if you get mitazalimab. This is significant and an important improvement for the patients, their families and loved one.

– Also important, the median overall survival increased to 14.9 months, further differentiating mitazalimab from standard of care. All other readouts like reponse rate and durability of response were either confirmed or, for most parameters, strengthened compared to the Janaury readout.

What is the key number that makes you believe that mitazalimab will become part of the standard regimen for pancreatic cancer patients?

– The substantial survival benefit reflected in the overall survival, durability of response and the long-term survival rates that, combined with a manageble safety profile, differentiates mitazalimab from competition and makes it the potential next standard of care in metastatic pancreatic cancer.

How clear is the immunotherapeutic contribution of mitazalimab when added to chemotherapy?

– It is pretty evident. Standard of Care FOLFIRINOX or NALIRIFOX have consistently reported median OS of roughly 11 months. The almost 15 months reported by mitazalimab combined with chemotherapy is therefore a strong improvement.

– Importantly we see clear evidence of immune activation in patients treated with mitazalimab. We have identified specific cell types that are activated and expanded in mitazalimab responders, but not in the patients that do not respond to treatment.

You are still on schedule to start phase III during Q1 next year. Can you update us on where things stand with the preparations?

– Yes, we are on track. Building on our interactions with FDA late last year, we have planned several meetings with european and US regulators in the second half of 2024. We are on the final phase of manufacturing sufficient mitazalimab for the phase 3 and we are about to complete the dosing of patients receiving low dose mitazalimab that the FDA asked us to conduct to complete the phase 3 dossier.

– Meanwhile we are continuing our partnering discussions which have been further fueled by the latest data, the Lancet paper and the presentations at ASCO and ESMO these last weeks so I believe we are in a good position to select the best partner for mitazalimab.

Speaking of Q1 2025, the company just announced a financing round to prolong its cash runway until then. How does this liquidity injection strengthen Alligator’s business development process?

– Pharma companies are particularly slow and cautious when it comes to licensing a product that could generate sales only in 4-5 years and is not certain of reaching the market. We therefore try to put all the chances on our side by both continuing to deliver outstanding data, but also provide us the time to discuss the best terms for our investors who have supported our vision over the last few years.

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.

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