The dark matter of the genome: Flamingo Therapeutics taps potential of mysterious RNA for cancer therapies

October 20, 2021 Article BioVox

Things are moving fast for Flamingo Therapeutics, a Leuven-based biotech company developing innovative RNA-targeted cancer therapies. The start-up is a pioneer in the field of lncRNAs, a large and untapped class of disease-causing targets within the so-called ‘dark matter’ of the human genome.

This article was authored by Andy Furniere.

Flamingo Therapeutics was born out of a collaboration between three partners in Flanders – VIB, UGent and KU Leuven – and the University of Michigan in the US. “The foundations of the company were laid in 2016, when the research groups of prof. Pieter Mestdagh at UGent and prof. Jean-Christophe Marine at VIB and KU Leuven published a paper revealing a connection between certain long non-coding RNAs and malignant melanoma, the most aggressive form of skin cancer,” explains Floor Stam, COO at Flamingo. These insights were later linked to research carried out at the University of Michigan.

Thanks to this unique expertise, the young biotech company is currently one of the only players in the world that is able to explore the potential of these long-coding RNAs (lncRNAs, pronounced as ‘link RNA’). According to Flamingo, lncRNAs account for 27% of the non-coding RNA genes, which make up around two-thirds of all genes. Non-coding RNA genes are not translated into proteins and the function of most of them is currently very unclear (hence the ‘dark matter’ moniker).

Cancer targets from out of the dark

“For a long time, the non-coding portion of the genome was considered to be useless ‘junk DNA’. But it actually has an enormous potential for new therapies against many different diseases,” says Stam. Flamingo is specifically looking into the possibilities for cancer therapies, as lncRNAs play a role in the energy provision of cancer cells when they divide uncontrollably. If you can manipulate that process, you should be able to produce a very targeted treatment that attacks the cancer cells and leaves healthy cells alone.

Flamingo’s approach could possibly limit the side effects of innovative cancer therapies. Stam also believes this new solution could be produced more rapidly than more traditional therapies that target proteins. “Because we have access to the unparalleled screening and hit identification capabilities of our collaborators at Ionis, a clinical candidate molecule can be developed in 12 to 14 months,” specifies Stam.

“For a long time, the non-coding portion of the genome was considered to be useless ‘junk DNA’. But it actually has an enormous potential for new therapies against many different diseases.” – Floor Stam, Flamingo Therapeutics

To identify targets for cancer therapies in this predominantly uncharted region of the genome, the company has developed the unique discovery engine FLAME (Flamingo LncRNA Antisense Mining Engine). Based on the findings in the groundbreaking 2016 paper, the initial focus has predominantly been on finding targets for treating the aggressive skin cancer melanoma, where the Flamingo team has been focusing on a lncRNA molecule named SAMMSON.

High profile partnership

Thanks to a recently-signed collaboration agreement with the American company Ionis Pharmaceuticals – a global leader in RNA-targeted therapies – Flamingo is now expanding its activities dramatically. The company is taking over three clinical programs for RNA-targeted cancer therapeutics from Ionis, as well as one preclinical program concentrating on lncRNAs.

“Ionis has been at the forefront of RNA-targeted therapy for thirty years… We are also a very interesting partner for them, because we concentrate on RNA-targeting therapies in oncology and have unique expertise in the field of lncRNAs.” – Mike Garrett, Flamingo Therapeutics

“From the start, Ionis has been a crucial shareholder of ours, helping us to go in the right direction,” says Mike Garrett, CEO of Flamingo. “Ionis has been at the forefront of RNA-targeted therapy for thirty years and offers invaluable knowhow and experience in clinical programs. We are also a very interesting partner for them, because we concentrate on RNA-targeting therapies in oncology and have unique expertise in the field of lncRNAs.” While Flamingo’s headquarters are located at the biotech incubator in Leuven, much of its activities also take place in facilities at San Diego close to Ionis’ home base.

Potential solutions for a range of cancer types

Flamingo’s most advanced drug candidate in development is called danvatirsen and targets the STAT-3 gene. “It is showing great potential in the battle against head and neck cancers and lymphoma,” says Garrett. Other drug candidates, targeting the androgen receptor and IRF4 gene, are being developed to fight prostate cancer and multiple myeloma (a type of bone marrow cancer).

Read this BioVox article to learn about Precirix, another start-up tackling cancer with an innovative approach.

The Flemish company has also taken over a preclinical-stage program focusing on a well-characterized lncRNA target named MALAT1. “This pioneering research could lead to solutions for different cancers, but for the moment we especially foresee therapeutic benefits for patients with triple-negative breast cancer,” says COO Floor Stam. The preclinical stage of this program should be finished by the end of 2022. In ideal circumstances, the clinical programs could lead to new therapies on the market already in 2026.

To support the company’s rapid expansion, Flamingo is now preparing a new investment round. For the moment, its main investors are the well-known biotechnology investors PMV and Kurma Partners, Belgian and French respectively.


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