Home Interviews FDA approves Alligator’s phase II trial

FDA approves Alligator’s phase II trial

Alligator Bioscience phase II trial approved

FDA approves Alligator’s phase II trial

11 April, 2023

Alligator BioScience continues to make headways with its lead cancer immunotherapy candidate mitazalimab. The company reported positive interim data from its phase II OPTIMIZE-1 trial in metastatic pancreatic cancer in January. Now Alligator has received FDA authorization to start a new phase II trial, OPTIMIZE-2, in urothelial carcinoma. BioStock reached out to Alligator’s CEO Søren Bregenholt for a comment.

The Swedish biotech Alligator Bioscience kicked off 2023 by presenting promising interim data from its OPTIMIZE-1 phase Ib/II study with lead drug candidate mitazalimab in metastatic pancreatic cancer. The CD40 agonist is being evaluated in combination with mFOLFIRINOX – the most common chemotherapy for pancreatic cancer patients. Alligator’s CEO Søren Bregenholt came to the BioStock Studio for an exclusive interview to talk about the results. You can watch the interview here.

To give even more insight on the OPTIMIZE-1 study design and overall results, Alligator’s CMO Sumeet Ambarkhane hosted a webinar last month alongside Dr Jean-Luc Van Laethem – the Principal Investigator for the study.

In a in-depth interview with BioStock, Dr Ambarkhane commented on the study results:

“I think the most important takeaway from the interim analysis is the strong signal it has generated, indicating clinically meaningful activity of Mitazalimab when added to the chemotherapy backbone mFOLFIRINOX.”

Read the whole interview here.

New indication for mitazalimab in phase II study

In order to hedge the medical risk and maximise the long-term value of mitazalimab, Alligator has been planning a second phase II trial in an additional cancer indication.

This week, the FDA approved Alligator’s IND application to start this new phase II study, called OPTIMIZE-2. The chosen indication is urothelial carcinoma – the most common type of bladder cancer. In fact, it accounts for approximately 90 per cent of bladder cancers, with 83,000 new patients and 16,700 deaths each year in the U.S.

While OPTIMIZE-1 seeks to test mitazalimab’s safety and efficacy in combination with chemotherapy, OPTIMIZE-2 will test the same but in combination with an immune checkpoint inhibitor (anti-PD-1). The study will take place in approximately 15 to 20 clinical sites across the U.S. and Europe. Objective response rate (ORR) will be the primary efficacy endpoint of the study.

Alligator’s stock price jumped by almost 12 per cent the day after the announcement of the IND approval.

CEO comments

To learn more about OPTIMIZE-2, BioStock got in touch with Alligator’s CEO Søren Bregenholt.

Søren, why is it important to start a new phase II trial with mitazalimab?

– Firstly we wanted to investigate the effect of mitazalimab in a different tumour type. The biology of urothelial and pancreatic cancer is rather different. Pancreatic cancers are “cold”  immune deserted tumour type which means that the immune system struggles to penetrate the tumours to destroy it. On the other hand, urothelial cancer are “hot” tumours which means they are more inflamed which allows the immune system to be stimulated by immunotherapies and to penetrate the tumour to help destroy it. Secondly, we wanted an opportunity to generate clinical data in combination with PD1 which have become the backbone treatment for so many tumour types, thus opening avenues to additional indications for mita.

Why was urotherlial carcinoma chosen as a second indication for mitazalimab?

– Preclinical data demonstrate that mita synergizes with PD1 in bladder cancer models, which together with additional mechanistic evidence strengthen the case for mita in mUC.

Søren Bregenholt, Alligator Bioscience
Søren Bregenholt, CEO Alligator Bioscience

– Clinically, PD1 inhibitors are used across multiple treatment lines in mUC, either as monotherapy or  maintenance after chemo. However, response to PD1 used as a single agent remains low with only 20-30 per cent of patients responding to it and a minority of patients benefit from a long disease-free survival. We believe that by activating the tumour microenvironment, mitazalimab will be able to reverse prior resistance to checkpoint inhibitor therapy, leading to deeper and longer clinical responses.

– We believe that a positive outcome of OPTIMIZE-2 would clear a path towards regulatory approval in mUC, and as I mentioned in the beginning support mita in multiple other tumour types, potentially even in earlier treatment lines to improve the clinical outcomes of patients.

OPTIMIZE-2 will evaluate mitazalimab’s safety and efficacy in combination with a PD-1 inhibitor, and not chemotherapy as in OPTIMIZE-1. Should we expect any differences in how the CD40 molecule behaves and produces its effect?

– First of all, we anticipate the mitazalimab, PD1 inhibitors combo to be safe, based on known data of the two agents. Biologically we expect no fundamental differences in how mitazalimab works between the two trials. Mitazalimab works by activating so-called dendritic cells in the tumour. Their role is to educate, activate and attract T-cells to more efficiently attack and eliminate the tumour. We have observed a synergistic effect with chemotherapy in the “cold” pancreatic cancer tumour and we expect to also see a synergistic effect in “hot” tumours in combination with PD-1.

Finally, you recently announced the intention to carry out a rights issue of approximately 200 MSEK. Will the proceeds be used towards both OPTIMIZE trials?

– That is a very important point indeed. Finalizing OPTIMIZE-1 and delivering phase 2 proof-of-concept data in pancreatic cancer by Q1 ’24 is what we are laser focused on right now and the proof of that is the faster than expected recruitment of patients, something which rarely happens in the world of Biotech. Being able to deliver unequivocally positive data with mita in Q1’24 will transform the company and it was critical to make sure we have sufficient financial resources to cross this finishing line. Financial markets are challenging for biotech though so we wanted to make sure that not only we had sufficient resources but also offer the opportunity to our existing shareholders, many of them who have supported us for many years, to participate in this last effort rather than reserving this opportunity to new coming investors.

– Regarding your question on whether this financing will be used to finance OPTIMIZE-2, the answer is no, it won’t as we plan to initiate the OPTIMIZE-2 study in the first half of 2024, or, if operationally feasible, maybe before but without interfering with our goal of delivering great data iin pancreatic cancer in Q1’24..

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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