"Dr Jekyll and Mr Hyde" technique to fight cancer

Viennese start-up develops novel, precise anti-cancer drugs

06-Mar-2023 - Austria

RIANA Therapeutics, a promising pharmaceutical start-up recently spun out of the University of Veterinary Medicine Vienna (Vetmeduni), aims to develop novel therapeutics for cancer patients based in part on scientific findings from Vetmeduni’s Moriggl research group (Moriggl Lab). The technological basis is a proprietary platform technology for the discovery of drugs that target cancer-causing protein-protein interactions (PPIs).

Computer-generated image

Dr. Jekyll and Mr. Hyde: novel targeted therapies against cancer. Any therapy must selectively target only the malignant ‘Mr. Hyde’ oncogenes (symbolic image).

Selectively targeting specific oncogenic PPIs has been an enormous challenge in pharmaceutical research. Anna Orlova, cancer researcher at Vetmeduni and co-founder and CEO of RIANA Therapeutics, wants to change that: “We have developed a unique cell-based phenotypic selection system that allows reliable screening for inhibitors that block the formation of specific cancer-causing PPIs.”

Dr. Jekyll and Mr. Hyde: novel targeted therapies against cancer

Tyrosine kinase inhibitors have been successfully applied in the treatment of cancer, confirming the benefits of targeted therapies. Many other potent oncogenes have not yet been targeted, however. One major reason is the “Dr. Jekyll and Mr. Hyde” problem of many PPIs. “A large class of PPIs involves proteins that are oncogenic only as oligomers (interaction of more than two proteins) but in other forms (e.g., as dimers, interaction of two proteins) are proteins that are vital to the biological functions of the body. As a result, any therapy must selectively target only the malignant ‘Mr. Hyde’ oncogenes. Our phenotypic screening system succeeds in targeting only these oncogenic forms,” explains Richard Moriggl, head of the Department of Functional Cancer Genomics at Vetmeduni and co-founder of RIANA Therapeutics.

STAT5B protein as a therapeutic target

The first molecule with a Dr. Jekyll and Mr. Hyde problem for which oligomerization inhibitors were successfully identified in the Moriggl Lab is STAT5B, a molecule that in its oligomeric form promotes the development of lymphomas, leukaemia and solid tumours. From a chemical library of 90,000 substances, several substances that inhibit STAT5B oligomerization were identified in a high-throughput screen using the novel screening system and are now being further developed by RIANA Therapeutics.

Anna Orlova, Co-founder and CEO of RIANA Therapeutics: "Targeting oncogenic PPIs such as STAT5B oligomerization is a novel, innovative approach to the discovery and development of effective and safe drugs against hematopoietic and other cancers. Because of the highly selective therapeutic model, we expect the compounds we develop to have significantly fewer side effects while maintaining good efficacy."

RIANA has its origins in 2018, when Anna Orlova and Richard Moriggl presented their promising research project “STAT5-inhibitors: Targeting STAT5 oligomerization in leukemia” at Vetmeduni’s VetIdeas Challenge. This was followed by a spin-off fellowship from the Austrian Research Promotion Agency (FFG), which enabled Anna Orlova to generate further data on her project. Orlova was accepted into the SCALEup incubator of the Vienna-based business incubator INiTS and underwent a training program there for future founders from the high-tech sector.

In 2022, the start-up team was awarded a substantial grant by AWS Seedfinancing, which enabled RIANA Therapeutics to be founded. VetWIDI Forschungsholding, a commercially oriented enterprise majority-owned by the University of Veterinary Medicine Vienna, is involved as a co-founder, bridging the gap between research and business and stimulating innovative entrepreneurship. Oliver Szolar, biotechnologist and successful multiple biotech entrepreneur, who has supported the project for many years, is also on board as co-founder and advisor.

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