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Alligator showcases bold drug development vision

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Alligator showcases bold drug development vision

8 December, 2023

Alligator Bioscience held its Capital Markets Day in Stockholm on December 1, 2023, offering investors, analysts, and media a comprehensive view of the company’s pipeline and drug development strategy. Alligator’s CEO Søren Bregenholt shared the company’s long-term plan through 2030. Here, Bregenholt gives BioStock an in-depth overview of the key takeaways from Capital Markets Day.

At its 2023 Capital Markets Day (CMD), Swedish biotech Alligator Bioscience drew attention to its extensive cancer immunotherapy development pipeline, most of which have either CD40 or 4-1BB as their molecular targets.

The focus for the CMD was mainly on the company’s lead asset, mitazalimab – a best-in-class CD40 agonist, but also focused on the significant opportunities beyond mitazalimab. Mitazalimab is being evaluated in first line metastatic pancreatic cancer patients, and it has been generating quite the buzz after the release of positive interim phase II data in 2023 and with the top-line phase II data expected in early Q1 2024.

Towards phase III with mitazalimab

As a guest during Alligator’s presentation, Dr Gregory Beatty, who is Director of Clinical and Translational Research at the University of Pennsylvania and has extensive experience with immunotherapy clinical trials in pancreatic cancer patients, pointed out mitazalimab’s strong safety and efficacy profile. As the OPTIMIZE-1 phase II study progresses, more patients are staying on the drug for extended periods, demonstrating mitazalimab’s potential to meaningfully extend the overall survival of patients.

Additionally, Dr Beatty emphasised the unique dosing regimen, the combination with FOLFIRINOX, and the patient population as key differentiating factors facilitating trial success. Dr Beatty also highlighted the fact that mFOLFIRINOX was increasingly becoming the new standard of care in the US in pancreatic cancer, making the OPTIMIZE-1 regimen that combines mitazalimab with mFOLFIRINOX highly relevant. Dr Beatty ended by stating that the obvious next step for the asset is a clinical phase III trial. For the latest on mitazalimab, read here.

Technology platforms and ATOR-4066

The CMD also touched upon Alligator’s technology programmes and the important partnerships aimed at developing these programmes further. CTO Laura von Schantz put the spotlight on Alligator’s collaboration with the Finnish biopharma company Orion. Through this collaboration, Alligator’s bispecific antibody platform is employed to develop novel immuno-oncology candidates.

Neo-X-Prime is another technology platform created by Alligator for the development of novel immunotherapy candidates targeting a wide range of cancer indications. Through the platform, bispecific antibodies are generated targeting CD40 along antigens expressed in a highly specific manner by the tumour, allowing the activation of the CD40 only at the heart of the tumour.

Alligator’s CSO Peter Ellmark spoke about ATOR-4066 – the first programme built upon the Neo-X-Prime platform. The candidate is still in preclinical development, but the data generated thus far reflect the synergistic effect of ATOR-4066 on T-cell activation when combined with a PD-1 checkpoint inhibitor, which is expected to not only boost the efficacy of PD-1 in tumours where these compounds are already approved, but also expand tumour types where PD-1 could be efficacious. According to Ellmark, “4066 takes full advantage of targeting CD40 to drive efficacy and safety in an optimal way.”

The 4-1BB target

Last, but not least, Alligator’s CMD featured a presentation by CMO Sumeet Ambarkhane about the company’s programmes involving the developing of cancer immunotherapy candidates targeting 4-1BB – an immune system activator. Alligator has two clinical assets targeting 4-1BB: ATOR-1017, which has completed phase I, and ALG-APV.527, a joint venture with Aptevo Therapeutics currently undergoing phase I.

According to Dr Ambarkhane, phase II trial preparations are underway for ATOR-1017, and the company is looking for a partner for this project. Meanwhile, interim data from ALG-APV.527 are expected in H1 2024 and topline data in H2 2024.

Upcoming value-inflection points

To top the day off, Alligator’s CEO Søren Bregenholt gave the audience a look at the company’s strategic outlook. According to Bregenholt, Alligator has “a pipeline with a lot of promise and with a lot of value-inflection points.” He believes that by 2030 the company will have three mid-stage assets in clinical development and five partnered assets. Moreover, approval for mitazalimab could come as soon as 2027-2028, meaning that Alligator should also be receiving income from the lead asset through milestones and royalties by 2030.

BioStock spoke with Søren Bregenholt to discuss some of these key points.

Søren, at the Capital Markets Day, Dr Beatty recommended a randomised phase III trial for mitazalimab based on the data presented so far. How can he give such a recommendation without having seen the final data set?

– Dr Beatty treats a lot of pancreatic cancer patients and understand what matters in terms of clinical benefit and safety. He has also been involved in a lot of clinical studies in the disease – so he knows what it takes for a molecule to make a real difference. Although he, like the rest of us, has not seen the full data yet, he apparently like the data he has seen and hat he sees and hears from the investigators.

Søren Bregenholt, Alligator Bioscience
Søren Bregenholt, CEO Alligator Bioscience

What would need to happen before a phase III trial could take place, and what would be an approximate timeline for a phase III start?

– Initiating a phase 3 study is not a trivial thing. A number of key elements need to be in place. Obviously we need see the phase 2 data in a few weeks, and agree on a trial design with the FDA and EMA. Those dialogues are underway. Thirdly we need the appropriate material for the trial, as discussed we have invested in the phase 3 manufacturing process and have made great process there. Finally, the financial resources need to be there. The most likely scenario is that phase 3 will be executed by a partner, and with all these required activities to take place, we would expect a phase 3 trial to be initiated in H1 2025.

You demonstrated optimism in having mitazalimab approved by 2028. What gives you such optimism?

– In a disease like pancreatic cancer where patients progress and die so quickly and with so limited therapeutic alternatives, it is not unrealistic to move from trial start to regulatory registration in less than four years, whether it is for accelerated approval or full approval. Of course it requires that all our stars are aligned.

You mentioned how ATOR-4066 could take CD40-based therapy to a new level. What do you mean by that?

– Yes, that is correct. The data we have seen so far point to a couple of interesting opportunities. First of all, the molecular design enables a very potent yet safe drug. ATOR-4066 has the ability, on it own, to eliminate large well-established tumours with heterogenous CEA-expression, moreover it can “awaken” exhausted immune cells in combination with PD1 inhibitors. In lemming terms that means that ATOR-4066 could significantly extend the efficacy of PD1 inhibitors, make immune cells work longer and more efficiently against the cancers, and could do this as a stand-alone drug – something that is not possible with the current CD40 mAbs.

When do you expect this candidate to reach the clinic?

– It will probably take a couple of years.

Alligator has already entered important agreements so far. Is entering new collaborations a prerogative for Alligator in the coming years?

– Many Biotech companies have the ambition to become full fledge commercial companies, but Alligator wants to remain focused on what we do best, which is to discover and develop highly innovative and potent drugs to fight challenging cancers. Getting a strong partner to drive the development of mitazalimab in pancreatic cancer, but also in other indications, will expedite the clinical development, optimise the commercial launch and allow as many patients as possible to benefit from this innovation. Proceeds from such deal will also allow Alligator to pursue the clinical development of its earlier stage pipeline and leverage further its very powerful technology platforms.

Finally, what is the main message you hope that investors take home with them after this Capital Markets Day?

– Firstly, that mitazalimab is set-up for success and that we have the next generation of innovative molecules ready to secure continued value creation. Secondly, that our technologies and pipeline provides a lot of optionality going forward. And finally I hope the enthusiasm, passion, and commitment of management and the entire Alligator team was evident in the room and virtually.

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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