REGEN-BY-2 will research, design, construct and experiment a first-of-its-kind lab-scale prototype of a recent near-worldwide patented thermodynamic cycle and related plant for the conversion of thermal sources in energy vectors, i.e. electric, heating and-or cooling powers. The start-up TIFEO, which was founded in 2018 by the team leading this proposal and is the exclusive licensee of the patent driving REGEN-BY-2, is a potential European Unicorn. REGEN-BY-2 can convert (from small to large-scale) any typology of renewable thermal source from low to high-temperature (e.g. solar, aerothermal, geothermal, hydrothermal) including additional thermal sources (e.g. waste heat). REGEN-BY-2 is enabled by machines capable to work with two-phase fluids, i.e. constituted by both liquid and vapor phases. The patented thermodynamic cycle is highly efficient as it is constituted by a proper combination of Carnot cycles operating with two-phase fluid circulating in novel two-phase expanders and two-phase compressors. To be successful, these two-phase machines will have to be designed, prototyped and integrated in the REGEN-BY-2 lab-scale prototype. Moreover, the patented technology has large flexibility due to the control of many process parameters, allowing chasing and satisfying the end-users energy demands in a predictable and dispatchable way. By the exploitation of renewable thermal sources from small to large-scale, by converting them more efficiently and with more flexibility into electric, heating and-or cooling energy vectors, REGEN-BY-2 will induce greater demand for and increasing use of renewable thermal sources. REGEN-BY-2 is a breakthrough in our energy infrastructure as it can be used in wide energy sectors (e.g. District Heating&Cooling systems and Distributed Renewable Flexible Energy systems). The research is low-TRL and high risk. For this, a full value international chain is assembled (Universities, RTOs, SMEs, Large Enterprises, a Standards Organization).