Evaxion Biotech’s lead immunotherapy candidate, EVX-01, developed through one of the company’s AI platforms, has entered clinical development phase IIb in metastatic melanoma patients. With the announcement of the first patient enrolled in the study, BioStock spoke with Evaxion’s CMO Erik Heegaard to learn more about this important milestone.

This past decade has seen the rise of immunotherapies for the treatment of cancer, in many ways revolutionising this enormous treatment field. Danish Evaxion Biotech aims at pushing this development even further with its award-winning AI-powered personalised approach.

The problem with current immunotherapies

One of the most common marketed immunotherapies for some types of cancer is the blockbuster checkpoint inhibitor (CPI) Keytruda (pembrolizumab), developed by Merck. This drug blocks a tumour’s ability to “hide” from a patient’s immune system.

However, not every tumour is the same. In fact, the mutations that characterise each tumour are unique in each individual. This is one of the key factors that makes cancer treatment so challenging to develop, and why many researchers are betting on personalised medicine. Unfortunately, CPIs like Keytruda only work in a subset of patients. In many indications, this leaves the majority of patients without appropriate medical therapy.

Using AI to find a new melanoma treatment

Thanks to Evaxion’s PIONEER AI platform, an immunotherapy candidate, EVX-01, was designed as a patient-specific therapy – a peptide that elicits a cancer-specific immune response. This gives EVX-01 the potential to work in combination with a CPI like Keytruda to boost a patient’s immune system enough to give cancer patients better survival chances.

Metastatic melanoma is the deadliest form of skin cancer. Today, despite the promise of marketed immunotherapies, roughly one half of patients with this disease do not respond to treatment. Thus, Evaxion’s discovery comes at a time when there is a strong need for better melanoma treatments.

In a phase I/IIa study with metastatic melanoma patients, EVX-01 showed an anti-tumour effect in most patients, with an objective response rate of 67 per cent when used in combination with a PD1 CPI. Two of the patients in the study, corresponding to 22 per cent of participants, achieved a complete response. Read more about the trial here.

First patient enrolled in phase II trial

Now the company has begun a phase IIb trial with EVX-01 at clinical sites across the US, Europe, and Australia. The efficacy and safety of the candidate will be evaluated in adults with metastatic melanoma, and the trial is being conducted in collaboration with Merck, which is supplying the trial with Keytruda. Patients will receive standard-of-care treatment, i.e., Keytruda, in combination with EVX-01.

Evaxion has announced that the first patient has been enrolled in the trial, marking a significant milestone for the company. BioStock reached out to Evaxion’s CMO Erik Heegaard to learn more about the trial and his expectations.

Erik, could you explain to our audience what EVX-01 is exactly and why it’s so promising?

– In the EVX-01 programme, we produce a peptide-based vaccine that is then repeatedly given to the patient. In our phase I trial we saw very limited side effects coupled with rather promising clinical signs, albeit in a small population. Please remember that for most of these patients they are literally at the end of the line meaning there are no other relevant treatment alternatives. To be able to then have patients that are improving after EVX-01 treatment is of course very encouraging.

What role did Evaxion’s AI technology play in discovering EVX-01?

– At Evaxion we have spent years in developing an AI-based tool that allows us to design fully personalised immunotherapy. Our AI tool, called PIONEER, accurately detects the most significant changes that are seen in a tumour and compares this to the patient’s normal genome and tissue type. PIONEER then predicts which changes hold the biggest potential when developing a vaccine directed against the tumour.

Could EVX-01 work independently, or is it meant to work in combination with Keytruda?

– In an oncology setting, we would always offer patients the standard of care, which typically involves CPI therapy, so it is not relevant for now to test EVX-01 as monotherapy. In fact, our current biological understanding suggests some synergy between CPI and EVX-01 in the sense that a CPI lifts the brake from the immune system. In contrast, EVX-01 concurrently trains the immune system to attack cancer cells. This means you hit cancer forcefully through two different modes of action.

And could it work with other immunotherapies as well?

– We are very grateful for the support offered by Merck in providing the World’s premier CPI Keytruda. We look forward to exploring how the addition of EVX-01 may further benefit patients. That said, in other settings, we have also combined EVX-01 with nivolumab, for example. This combination expectedly should perform equally well.

Why was metastatic melanoma chosen as the first indication for EVX-01?

– Melanoma is a disease with a substantial unmet medical need. It is also a very common disease, so the cumulated need for better therapy is staggering, and this, of course, also translates into a compelling market opportunity. Furthermore, melanoma cancers harbour a high mutational burden, making it more feasible when detecting the necessary changes used to train the immune system. In a way, this type of tumour offers more opportunities for the attack through immunotherapy.

How significant is this milestone of enrolling the first patient for the phase II study with EVX-01?

– The enrolment of the first patient marks the next step in a journey that we hope will lead to developing new and efficacious treatments against malignant melanoma. Once the trial is completed, we will be able to assess this approach’s potential to cure cancer.

What timeline can we expect for this study, and do you expect to see similar efficacy results as you did from the phase I/II trial?

– Timelines in clinical development seem very extended when you’re eager to explore and improve treatments for patients in need. However, recruiting a sufficient number of patients and keeping them on the therapy for two years simply dictate the timeframe in which we operate. That said, we expect to share interim data about a year from now and will continue to do so at regular intervals. We must respect the scientific process and results from this trial, yet I remain hopeful that we will continue to offer melanoma patients a meaningful clinical benefit.

Finally, what comes next for EVX-01? Are new indications going to be considered?

– We will first explore the performance of EVX-01 in melanoma patients. Guided by these results, it is definitely within reason to potentially expand the indications in the future. Moreover, we have a DNA-based clinical development program focused on lung cancer, another indication with dire prospects and a need for improved therapy. Essentially, our AI platform is agnostic in terms of the treatment modality. We plan to investigate multiple therapeutic avenues, such as mRNA vaccines on top of our peptide- and DNA-based vaccines.

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