Huge Series A in France Strengthens European Epigenetic Oncology

epigenetics oncology car t mnemo therapeutics

Mnemo Therapeutics has raised €75M in the largest-ever French Series A round, which it will use to develop CAR-T cell immunotherapies for cancer using epigenetic targets.

Mnemo Therapeutics’ mammoth financing, led by Casdin Capital, returning investor Sofinnova Partners, and an undisclosed investor, will allow the startup to accelerate the development of its epigenetic targeting and next-generation cell immunotherapy platform. The round will also help the firm develop its preclinical portfolio in both solid and liquid tumors. 

The goal is to be IND- and phase I-ready by the end of 2023 for at least two projects,” said Alain Maiore, CEO of Mnemo Therapeutics. He added that these initial therapies will target undisclosed cancer antigens that are already known, with trials of treatments targeting the company’s novel epigenetic antigens expected to follow in 2024.

Epigenetics refers to small, reversible modifications to DNA molecules that change the way genes are expressed without altering the genetic code itself. These epigenetic processes are seeing increased interest in the oncology space as they can provide targets for cancer therapies. At the start of June, for example, AstraZeneca recruited the German firm Proteros biostructures to co-develop cancer drugs that hit epigenetic targets.

“Advances in epigenomic capabilities will bring forward the next wave of innovation in cancer development through the discovery and development of novel small molecules,stated Susan Galbraith, AstraZeneca’s Senior Vice President and Head of Research and Early Development, Oncology R&D.

Proteros’ proprietary discovery platform enables us to screen epigenetic targets in a physiologically relevant setting, supporting accelerated discovery and development of the next wave of anti-cancer medicines,” she added.

At the end of March, US-based Omega Therapeutics closed an upsized Series C financing of €106M ($126M), which will support the advancement of the company’s lead epigenetic candidate. The drug is engineered to specifically control the expression of an oncogene implicated in cancer development.

Several drugs have been approved to treat cancer by disrupting epigenetic regulators in cancer cells, such as vorinostat and romidepsin. Mnemo Therapeutics applies its own epigenetics expertise to chimeric antigen receptor (CAR)-T cell immunotherapies, in which a patient’s T cells are engineered to carry a cancer-hunting CAR protein on their surface. When the CAR detects a target on a cancer cell, the T cell is stimulated to attack the tumor cell.

What is different [with Mnemo Therapeutics] is that we are knocking out a particular epigenetic regulator in CAR-T cells to increase their persistence, which we know is important for greater efficacy in patients,” Maiore explained.

Despite many advances in drug target optimization, CAR-T cell therapy lags way behind other cancer immunotherapies in terms of regulatory approvals. Just three drugs are approved for blood cancer in Europe — Yescarta, Kymriah, and Tecartus — while the FDA approved its fourth and fifth CAR-T cell therapies earlier this year: Breyanzi and Abecma. Reasons for this slow progress include a tricky regulatory environment and expensive manufacturing processes. 

Another challenge with CAR-T cell therapy has been the cancer becoming resistant to the treatment. This can happen when mutations lead to a reduced density or even a complete loss of the cell therapy’s target on the tumor cells. 

According to Maoire, one way for Mnemo to overcome the complete loss of a target is developing CAR-T cell therapies against multiple targets on the tumor cell. To tackle reduced target density, Mnemo has “developed an antigen-recognition technology that can kill cells with very low levels of [target] antigens, thereby preventing tumor escape,” Maiore added.

Meanwhile, there are also drug discovery challenges to overcome in working with epigenetic targets in oncology. According to Debora Konz Makino, Head of Discovery Solutions Business Unit at Proteros, these targets “are often not amenable to small molecule inhibition and they frequently have close family members, which makes obtaining selectivity challenging.”

According to Coherent Market Insights, the global epigenetic technologies market was valued at €5.7B ($6.8B) in 2019 and is estimated to grow by almost 20% per year between 2020 and 2027. The USA has the largest market share, with Bristol-Myers Squibb’s Celgene subsidiary and its spinout Regenacy Pharmaceuticals among the key players.

Nonetheless, Antoine Papiernik, Chairman and Managing Partner at Sofinnova Partners, told me that “Europe is on par with the US on this science, if not ahead.”

Mnemo, a Paris-based company, is again a good example of the fact that Europe can also be on par on the financing of this science,” Papiernik added.

As well as Mnemo and Proteros, Europe has companies like 4SC, Astex Pharmaceuticals, CellCentric, Celleron Therapeutics, Chroma Therapeutics, and Oryzon Genomics all driving momentum to create new tools in the fight against cancer.

Cover image from Elena Resko.

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