Over the past decade, the number of immunotherapies for the treatment of cancer has increased, which in many ways has revolutionized this huge field of treatment. Danish Evaxion Biotech aims to drive this development even further with its award-winning AI-powered patient-specific approaches.
The problem with current immunotherapies
One of the most commonly marketed immunotherapies for certain types of cancer is the blockbuster checkpoint inhibitor (CPI) Keytruda (pembrolizumab), which has been developed by MerckThis drug blocks a tumor's ability to "hide" from the patient's immune system.
But, tumors are different. In fact, the mutations that characterize each tumor are unique to each individual. This is one of the key factors that makes cancer treatments so challenging to develop, and why so many researchers are investing in personalized medicine. Unfortunately, CPIs like Keytruda work in some patients, but not in others.
Unfortunately, CPIs like Keytruda only work for certain subsets of patients. For many indications, this means that the majority of patients do not receive appropriate medical treatment.
Using AI to find a new melanoma treatment
Using Evaxion's AI platform PIONEER the immunotherapy candidate was designed EVX-01 as a patient-specific neo-antigen therapy – a peptide that elicits a cancer-specific immune response. This gives EVX-01 the potential to be combined with a CPI like Keytruda to boost the patient's immune system enough to give cancer patients a better chance of survival.
Metastatic melanoma is the deadliest form of skin cancer. Despite promising immunotherapies, only about half of patients with this disease respond to treatment. Evaxion's discovery comes at a time of great need for better treatments for melanoma.
In a Phase I/IIa study in patients with metastatic melanoma, EVX-01 demonstrated antitumor efficacy in most patients, with an objective response rate of 67 percent when used in combination with a PD1-CPI. Two of the patients in the study, representing 22 percent of the participants, achieved a complete response. Read more about the study here.
First patient recruited to Evaxion's Phase II study
Evaxion has now initiated a Phase IIb study with EVX-01 in clinics in the US, Europe and Australia. The candidate will evaluate the efficacy and safety in adults with metastatic melanoma, and the study is being conducted in collaboration with Merck, which is providing the study with Keytruda. Patients will receive standard of care, i.e. Keytruda, in combination with EVX-01.
Evaxion has announced that the first patient has been recruited to the study, which is an important milestone for the company. BioStock contacted Evaxion's CMO Erik Heegaard to find out more about the study 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 program, 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 developing an AI-based tool that allows us to design fully personalized immunotherapy. Our AI tool, called PIONEER, accurately detects the most significant changes that are seen in a tumor 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 tumor.
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 cumulative need for better therapy is staggering, and this, of course, also translates into a compelling market opportunity. Furthermore, melanoma cancers harbor 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 tumor 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 enrollment 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.