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Ultimovacs in the fight against mesothelioma

Ultimovacs i kampen mot mesoteliom

Ultimovacs in the fight against mesothelioma

2 June, 2023

Mesothelioma is a rare but aggressive form of cancer with limited treatment options. Norwegian biotech Ultimovacs is addressing the need for new therapies with its universal cancer vaccine UV1. BioStock got in touch with the Director Medical Affairs at Ultimovacs, Espen Basmo Ellingsen, to learn more about the overall burden caused by this disease as well as the phase II trial NIPU evaluating UV1 in combination with standard of care.

Asbestos is a naturally-occurring mineral known for its heat-trapping and anti-corrosive properties. During the 19th century and much of the 20th century, asbestos was commonly used as an insulating material for construction purposes, as well as other industrial applications.

The toxic, carcinogenic properties of asbestos were discovered and studied in the early 1900s when researchers noticed a large number of early deaths and lung problems in asbestos-mining towns. However, it was not until the latter part of the century that many governments, including those in the US and the EU, instituted severe restrictions and even total bans on the use of asbestos.

Despite those bans, the average latency period for the development of any health issues related to asbestos exposure is around 40 years. This translates to an elevated risk of health complications for past and current blue-collar workers who have come in direct contact with asbestos. Those within the construction industry are mostly affected, but so are civil service workers, firefighters in particular.

Mesothelioma – a deadly disease

One of the leading causes of death from asbestos exposure is mesothelioma, an aggressive form of cancer that develops in the lining of internal organs. The most common type of mesothelioma is malignant pleural mesothelioma (MPM), which affects the thin layer of tissue that surrounds the lungs and the inside of the chest. The disease often leads to a life expectancy of less than one year after diagnosis, and 5-year survival is 12 per cent.

MPM is so aggressive that it is usually diagnosed in the late stages, making treatment extremely challenging. By then, surgery is possible, but it is usually accompanied by chemotherapy. And as of 2020 in the US and 2021 in Europe, immune checkpoint inhibitors like nivolumab and ipilimumab have also become first-line treatments.

However, even if these therapies can make the cancer retreat at first, recurrence is highly likely. Upon relapse, the disease becomes more resistant to treatment, escaping the defences of the immune system, therefore reducing survival chances even further. Unfortunately, as of today, there is no standard treatment protocol for relapsed malignant mesothelioma, meaning that there is a significant medical gap to fill.

Ultimovacs’ cancer vaccine

Striving to fill this gap is Ultimovacs. The Nordic biotech is developing UV1, a universal cancer vaccine aimed at boosting a patient’s immune system enough to put the brakes on cancer. The company has five ongoing phase II clinical trials evaluating UV1 within different cancer indications – the NIPU trial is the one focused on mesothelioma.

Read more about Ultimovacs and its pipeline here.

The trial evaluates UV1 as a second-line treatment in combination with both checkpoint inhibitors nivolumab and ipilimumab. The research done with UV1 so far suggests that the therapeutic vaccine is able to work together with the immune checkpoints to unleash the full power of the immune system to attack cancer if it were to relapse.

An initial readout from the study is expected in the coming weeks. The results, if positive, will be proof-of-concept for UV1 in this indication, and a major step forward in the development of the vaccine.

A conversation with Ultimovacs’ DMA

BioStock reached out to Ultimovacs’ Director Medical Affairs Espen Basmo Ellingsen to discuss the challenges related to mesothelioma and how to treat it, as well as expectations for the NIPU trial.

Espen Basmo Ellingsen
Espen Basmo Ellingsen, Director Medical Affairs at Ultimovacs

Espen, why is mesothelioma such a difficult disease to treat?

Mesothelioma is a rare and aggressive disease characterized by irregular growth of the mesothelial cells, which form the protective lining of internal organs. The early symptoms of mesothelioma can be similar to those of less severe respiratory conditions. Mesothelioma, therefore, often goes undiagnosed in its early stages, and by the time a definitive diagnosis occurs, the cancer is typically more advanced, resulting in fewer therapeutic options and an established tumor biology that is harder to treat. Mesothelioma has shown to harbor genetic and molecular characteristics that make the cancer cells less susceptible to conventional treatments. For immunotherapies specifically, the tumors may hold certain immunosuppressive features that counteract the spontaneous anti-tumor immune responses.

What is the difference between first-line and second-line treatment in cancer therapy?

Treatment lines refer to the order treatments are given as a tumor progresses or recurs. For advanced cancers, first-line treatment refers to the initial treatment alternative a patient receives after diagnosis, whereas second-line treatment refers to the treatment alternative the patient receives after the disease progresses on first-line treatment. Each successive treatment line is initiated when the previous treatment is no longer effective or the disease has shown resistance to it. The goal of the different treatment lines is to provide additional therapeutic options to control the disease and extend survival. However, generally, the later the treatment line, the less response to therapy is expected.

Why isn’t UV1 being evaluated as a first-line treatment?

The NIPU trial evaluates UV1 in combination with nivolumab and ipilimumab as second-line therapy. At the time the trial was initiated, there were no approved immunotherapies for malignant pleural mesothelioma. It is common to evaluate experimental treatments in later treatment lines, when standard treatment options have been exhausted. However, with the recent approval of the checkpoint inhibitors nivolumab and ipilimumab as first-line therapy, positive results from the NIPU trial may facilitate further development of UV1 in the first-line setting.

Why is NIPU looking at UV1 in a triple combination with both nivolumab and ipilimumab, and not in combination with chemotherapy or even on its own?

Nivolumab and ipiliumab represent drugs that are classified as immune checkpoint inhibitors. Physiologically, the immunological checkpoints are the body’s way of containing T cell responses within a desired range, maintaining a balance between attacking harmful invaders and avoiding unnecessary damage to healthy cells. During the development of cancer, however, tumors exploit these checkpoint molecules to evade an attack from the patient’s T cells. When a patient receives a checkpoint inhibitor, naturally occuring T cells targeting the tumors can be released from these contraints, leading to cancer cell killing. Although many patients experience durable responses to checkpoint inhibition, unfortunately, most patients progress due to an insufficient natural immunity against the tumors.

Therapeutic vaccination with UV1 induces T cell responses that aim to strengthen the overall anti-tumor immune response. The combination of UV1 and the checkpoint inhibitors is based on a scientific rationale that releasing the immune cells from these immune checkpoints will result in stronger immune responses after vaccination, and that these immune cells will more effectively kill cancer cells. Although both being checkpoint inhibitors, the two drugs differ in the immune checkpoint molecule they block. Ipilimumab blocks CTLA-4, whereas nivolumab blocks PD-1. Blocking CTLA-4 is expected to strengthen the immune response after vaccination, whereas blocking PD-1 is expected to reduce the tumors ability to resist the induced immune response. With the characteristic features of mesothelioma, we believe the triple combination may be necessary to overcome the immunosuppressive tumor microenvironment and provide tangible cancer cell killing.

When can we expect top-line results from NIPU?

Topline results from the NIPU trial is expected to occur this month of June, so rather soon.

If the study brings positive results, what will it mean for UV1 and the future development, especially considering that mesothelioma is considered a rare disease?

If the NIPU trial reads positive:

it will prove the overall concept of UV1 as a telomerase targeted vaccine works when added to CPIs, and increases the probability of success in the other indications

further development plans will be discussed with the regulatory authorities to ensure the most effective and speedy way forward. This also includes filing for breakthrough/fast track designation, and orphan drug designation

it will definitely trigger further support for bringing UV1 to mesothelioma patients, a population with a true unmet medical need.

The imminent read-out of the NIPU trial represents the first-ever randomized data package on the UV1 vaccine. Following closely are the read-outs of the randomized INITIUM trial in melanoma (H2 2023) and the randomized FOCUS trial in head and neck cancer (H1 2024). The DOVACC and LUNGVACC trials are expected to complete later in 2024 and 2025, respectively. The outcomes of all these trials will guide the broader development of UV1.

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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