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FDA godkänner Alligators fas II-studie

Alligator Bioscience phase II trial approved

FDA godkänner Alligators fas II-studie

11 april, 2023

Alligator BioScience fortsätter att göra framsteg med sin ledande cancerimmunterapikandidat mitazalimab. Bolaget rapporterade positiva interimsdata från sin fas II-studie OPTIMIZE-1 i metastaserad bukspottskörtelcancer i januari. Nu har Alligator fått tillstånd från FDA att starta en ny fas II-studie, OPTIMIZE-2, inom urinblåsecancer. BioStock kontaktade Alligators vd Søren Bregenholt för en kommentar.

Det svenska bioteknikbolaget Alligator Bioscience inledde 2023 med att presentera lovande interimsdata från fas Ib/II-studien OPTIMIZE-1 med ledande läkemedelskandidaten mitazalimab i metastaserad bukspottskörtelcancer. CD40-agonisten utvärderas i kombination med mFOLFIRINOX – den vanligaste kemoterapin för patienter med bukspottkörtelscancer. Alligators vd Søren Bregenholt besökte BioStocks studio för en exklusiv intervju om resultaten. Se intervjun här.

För att ge ytterligare i insikt OPTIMIZE-1-studiens design och övergripande resultat  stod Alligators CMO Sumeet Ambarkhane värd för ett webbinarium förra månaden tillsammans med dr Jean-Luc Van Laethem – studiens huvudprövare.

I en intervju med BioStock kommenterade Dr Ambarkhane studieresultaten:

“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.”

Läs hela intervjun här.

Ny indikation för mitazalimab i fas II-studie

För att minska den medicinska risken och maximera det långsiktiga värdet av mitazalimab har Alligator planerat en andra fas II-studie i ytterligare en cancerindikation.

I veckan godkände FDA Alligators IND-ansökan om att starta denna nya fas II-studie, kallad OPTIMIZE-2. Den valda indikationen är urinblåsecancer – den vanligaste typen av cancer i urinvägarna. Denna typen av cancer utgör cirka 90 procent av blåscancerfall, med 83 000 nya patienter och 16 700 dödsfall varje år i USA.

Medan OPTIMIZE-1s syfte är att testa mitazalimabs säkerhet och effekt i kombination med kemoterapi, kommer OPTIMIZE-2 att testa detsamma men i kombination med en immuncheckpointhämmare (anti-PD-1). Studien kommer att äga rum på cirka 15 till 20 kliniker i USA och Europa. Studiens primära effektmått kommer att vara objektiv responsfrekvens (ORR).

Alligators aktiekurs steg med nästan 12 procent dagen efter tillkännagivandet av IND-godkännandet.

Vd kommenterar

För att få veta mer om OPTIMIZE-2 kontaktade BioStock Alligators vd 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, vd 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..

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