Posters on preclinical data on RVU305 and Synthetic Lethality Programspresented at the 2025 AACR Annual Meeting

The Management Board of Ryvu Therapeutics S.A., headquartered in Kraków(the "Company," "Ryvu"), in reference to current report no. 7/2025 datedMarch 26, 2025 informs that the Company has presented preclinical dataon RVU305 program and on its; synthetic lethality platform at the 2025AACR Annual Meeting, which takes place on April 25-30, 2025, in Chicago,United States.

Details on poster presentations are as follows:

Poster Title:"Preclinical candidate RVU305, an MTA-cooperative PRMT5inhibitor, shows activity in MTAP-deleted tumors resistant to immunecheckpoint treatment."

Session Name: HDAC and Methyltransferase Inhibitors

Session date and time:Tuesday, April 29, 9:00 AM - 12:00 PM EST

Poster Number:17

RVU305, a potentially best-in-class, brain-permeable MTA-cooperativePRMT5 inhibitor, demonstrates significant potential in targetingMTAP-deleted cancers. In preclinical studies, RVU305 effectivelyinhibited tumor growth in MTAP-null cancer models without affectingnormal cells. RVU305 also demonstrated CNS penetration with predictedefficacious exposure in the brain in cynomolgus monkeys. In CNS celllines, RVU305 exhibited high potency and efficacy. Furthermore,co-treatment with an anti-PD-1 antibody was well tolerated and resultedin antitumor activity in an MTAP-deleted model resistant to immunecheckpoint inhibitors (ICI). The efficacy of RVU305 was supported bypharmacodynamic changes observed in tumor tissue. These results positionRVU305 as a promising therapeutic option for patients carryingMTAP-deleted cancers resistant to ICI.

Poster Title:"Discovery of novel synthetic lethal targets for effectiveand safe colorectal cancer therapies."

Session Name: Experimental and Molecular Therapeutics

Session date and time:Monday, April 28, 2:00 PM - 5:00 PM EST

Poster Number: 3

This study highlights the discovery and validation of novel therapeutictargets for colorectal cancer (CRC) through synthetic lethal (SL)interactions, addressing the urgent need for more effective andpersonalized treatment options. The team identified key vulnerabilitiesin CRC using advanced models, including genetically engineered humanintestinal stem cells (hISCs) and patient-derived xenografts (PDXs) incombination with CRISPR/Cas9 technology.

Genome-wide SL screens revealed targets associated with common CRCdriver mutations, particularly APC and KRAS. These findings wererobustly validated. Notably, knock-out of the identified targetselectively killed mutant patient-derived cells while sparing healthyintestinal stem cells, demonstrating a favorable therapeutic window.

Furthermore, we identified small-molecule inhibitors that block theactivity of the newly discovered target. These compounds modulatedownstream biomarkers and phenocopy the differential effects observed inour genetic studies, supporting this approach's translational potential.

Together, these results lay the groundwork for developing targetedtherapies tailored to the genetic makeup of CRC tumors.

All posters are now available online and can be obtained from theconference site:

https://www.aacr.org/

Disclaimer: This English language translation has been prepared solelyfor the convenience of English-speaking readers. Despite all the effortsdevoted to this translation, certain discrepancies, omissions orapproximations may exist. In case of any differences between the Polishand the English versions, the Polish version shall prevail. RyvuTherapeutics S.A., its representatives and employees decline allresponsibility in this regard.