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Dear Ryvu Investors, Business Partners and Friends,
I would like to inform you that yesterday the management board of Ryvu Therapeutics S.A made a decision to prioritize our preclinical pipeline. As a consequence, we will stop the development of two projects: a dual adenosine receptor antagonist (A2A/A2B), that has so far completed non-GLP toxicology studies, and the project in the area of synthetic lethality (SMARCA2) at discovery stage. We have made this decision after additional feedback with the Supervisory Board of the Company during a meeting last week.
As a result of the pipeline’s revision, the Company will be able to concentrate its human and financial resources, including proceeds from the series I follow-up offering, on the SEL120 project, currently in Phase I clinical trials as well as the remaining preclinical projects, further support SEL24 development by Menarini, and assign financing to newly initiated discovery and development projects in the area of synthetic lethality. The company has already started working on new, confidential targets, which in our opinion, will have a greater chance to develop into new, first-in-class therapeutic options for the patients, with a good preclinical and clinical development possibility, and provide an additional partnering opportunities with biotech and pharma companies.
The strong cash position we have built through the recent follow-on offering provides Ryvu with 2 years’ of cash runway irrespectively of any potential milestones from the current and future partnering collaborations new grant funding.
We are planning to increase our headcount in the clinical development and discovery teams as well as complete the investments in the fully owned animal facility and doubling screening potential in our newly built research center in Krakow.
At Ryvu we want to allocate our discovery team, capital raised from investors and public support sources as well as our state of the art research infrastructure on projects that have the biggest potential in our pipeline. We constantly analyze each program from the perspective of unmet opportunities of cancer patients, strong and validated biological hypothesis, compound activity in relevant disease models, expected therapeutic index and possible additional safety risks, general developability, intellectual property position as well as future market potential and competitive environment. Internal analysis is supported by insights from our supervisory board as well as external key opinion leaders.
Through this process we are able to double down on the programs with the best overall competitive position, prune the weaker opportunities and pursue new opportunities that fit best key Ryvu strengths and our long term strategy.
 
Our adenosine program, initiated in 2016 used the third generation approach to immune evasion mediated by A2A and A2B receptors. We have believed that our pre-clinical candidate RVU330. a molecule strongly antagonizing both receptors which maintains its activity at biologically relevant adenosine concentrations will offer significant benefit over other programs, especially 2nd generation programs from ITeos and Arcus which have recently entered clinical development. After a thorough analysis we came to a conclusion that the totality of the data we have generated on RVU330 as well information available from external sources  does not warrant pursuing further IND-enabling studies and that it is too late to characterize another back-up.
 
In SMARCA2 project we were working on small molecules and degraders which were going to use the synthetically lethal relationship with SMARCA4 which s one of the most frequently mutated genes in lung cancer and other tumors. We were very excited with the initial biology work and proceeded to multi-track chemical approaches but after many tries we simply hit the wall, banged our heads on it for several quarters and with heavy heart decided to stop. SMARCA4 mutation is a great
target to pursue with different synthetically lethal approaches and we really hope hat someone else will drug it soon successfully and develop in the clinic. We have several noble companies in the race here and we wish them well.
 
At the same time our efforts in targeting SMARCA  have enabled us to build strong synthetic lethality expertise inside Ryvu which we are using for other projects in the pipeline, most notably WRN. We have also recently launched new programs in that space on undisclosed targets, including some with no disclosed third party programs. We believe that these programs are foundational for the long term future of Ryvu.
 
I would like to thank everyone at Ryvu and our external support network for their hard work on adenosine and SMARCA2 programs, program champions, authors of key positive breakthroughs and especially those who have designed killer experiments and analysis that made the decision of not pursuing these projects easier. We are especially grateful to the Polish National Center for Research and Development which has supported both projects with approximately $7M of research and development non-dilutive grant funding.
 
With best regards,
 
Pawel Przewiezlikowski