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Curevac starts a new attempt in cancer research

Frankfurt Tübingen-based Curevac AG has fallen far behind in cancer research in recent years, as it has in the vaccine sector. But here, too, the biotech company has now started a new attempt: “Oncology is the area that we will expand in a targeted manner alongside vaccines for infectious diseases,” said company boss Franz-Werner Haas in an interview with the Handelsblatt. The aim is to have new cancer vaccine candidates in the pipeline by the end of next year.

An elementary part of the strategy are two deals that the Tübingen-based company agreed with young biotech companies from the Benelux region in recent weeks. This includes an alliance with the Belgian company Myneo and the takeover of the Dutch start-up Frame Cancer Therapeutics for 32 million euros.

Both companies specialize in identifying so-called antigens on cancer cells. Frame uses modern sequencing technology for this. Myneo relies on data analysis and the use of artificial intelligence.

Antigens are molecular structures, usually proteins, that can be recognized by immune cells. As a starting point for possible immunotherapies against cancer, researchers are trying to find antigens that are particularly common on tumor cells, or – what is even better – due to mutations only arise on tumor cells but not in healthy tissue.

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In this case we are talking about neo-antigens. The basic idea is to use mRNA vaccines to target immune cells to such neo-antigens and thus target the cancer cells.

High hurdles for mRNA vaccines against cancer

The challenges for the mRNA companies are much greater than in the field of infectious diseases. Because cancer diseases are characterized by much greater heterogeneity and sometimes high mutation rates. For mRNA drugs, it is therefore not only important to activate immune cells sufficiently, but also to direct them to the right targets.

Another hurdle is influencing the tumor environment in such a way that the immune cells can actually become active there and are not paralyzed by certain signaling substances from the cancer cells.

So far, no mRNA drug against cancer has been approved. However, following the success of Covid vaccines, confidence has increased significantly among the leading mRNA companies.

Biontech boss Ugur Sahin, for example, recently expressed confidence in an interview with the Handelsblatt that it will be possible to bring several products to the market in the cancer field in the next few years. The Mainz-based company started out in 2008 with a strong focus on the search for antigens, has since been working intensively on bioinformatics solutions for tumor analysis and is now running around 20 clinical projects in the field of oncology, including individualized cancer vaccines, some of which are in phase 2 -Studies are tested.

>> Read the interview with the Biontech boss here: Biontech-Boss: This is how mRNA is supposed to help against cancer

In contrast, Curevac – similar to the development of the Covid vaccine – has largely failed with its cancer projects. A first mRNA vaccine flopped in a larger study against prostate cancer in 2017 because the immune response that was triggered was not strong enough and the selected antigen proved to be unfavorable.

The pharmaceutical partners Boehringer and Eli Lilly have exited partnerships with Curevac in the past two years. The only clinical project remaining in the pipeline was an RNA construct that has now been tested in a phase 1 study for five years as a general immune booster, but not as a targeted mRNA vaccine.

Regardless, Haas is optimistic that Curevac can make up ground again. In his view, the starting position has ultimately improved significantly as a result of the Covid pandemic, because additional know-how in the mRNA area, more mature production structures and new technologies are available. “We have never given up in oncology and will use our expertise in Covid vaccine development and the new possibilities in the field of genome sequencing and bioinformatics in a focused manner to advance the development of novel cancer vaccines,” he says.

Cancer cells are completely sequenced

The new subsidiary Frame will play a key role in this. The Dutch company specializes in the complete sequencing of cancer cells and the analysis of larger shifts, so-called frame shifts, in the genome of tumor cells.

Company founder Ronald Plasterk points out that these shifts result in numerous neo-antigens that have not been identified with previous analysis methods aimed at selective gene mutations and could therefore offer promising new targets for mRNA-based cancer vaccines. “By looking at the entire genome of the tumor cells, the chance is greater than if we only analyze a part.”

Haas sees the RNA printer currently being developed as an ideal complement to the frame technology – a system which, according to Curevac, allows particularly fast and largely automated production of mRNA molecules, for example for clinical studies or also for individualized therapies. The RNA printer will be certified by the authorities by the end of the year.

Improved mRNA backbone

For its future cancer vaccines, Curevac wants to use a new, improved mRNA framework that is currently also being used for a new Covid vaccine and a flu vaccine. These two products are in the early stages of clinical testing and are both being developed through a partnership with British pharmaceutical giant GSK.

Success in the oncology area would be very important for the Tübingen-based company in order to build up a new product pipeline outside of the GSK alliance and thus also create options for new partnerships. However, the financial starting conditions for this are significantly less favorable than those of the competitors Moderna and Biontech. Thanks to their successful Covid business, they now have financial reserves in the tens of billions.

In contrast, Curevac started the second quarter with cash and cash equivalents of just EUR 658 million. Cash consumption was most recently at 150 million euros per quarter, but is likely to decrease after the high investments for setting up production and processing the first Covid vaccine project have been largely completed. Financially, however, the oncology strategy should prove to be a tightrope walk. Because in terms of personnel, the Tübingen company has so far remained on an expansion course despite the setbacks in the Covid area. The number of employees has increased further compared to the previous year to around 1100.

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Haas speaks of a “controlled and very focused” expansion and sees the company as sufficiently equipped for the new ambitions in cancer research. A framework agreement with the US banks Jefferies and SVB Leering to issue additional shares with a volume of up to 600 million dollars offers a certain amount of leeway in financing, which, however, exceeds the shares of the previous owners, including SAP founder Dietmar Hopp with around 44 percent and the state-owned KfW with around 16 percent, would be diluted relatively strongly.

With a price of just over 14 dollars, the Curevac share is now almost 90 percent below its previous high and around nine percent below the issue price at the IPO.

After all, it could still be used as an acquisition currency in the case of the Frame takeover. According to company boss Plasterk, the frame investors were even very satisfied with being paid out in Curevac shares. “You could also see that as a sign of trust that wonderful synergies arise from the combination.”

More: Biontech boss Ugur Sahin: “Be prepared for the fact that we always need booster vaccinations”

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