• Two papers, published in The Lancet and Nature, indicate that treatment with oral raloxifene, a selective estrogen receptor modulator (SERM) with a proven safety profile, may be efficacious against SARS-CoV-2 clinically relevant variants.

• Raloxifene was identified as a potential COVID-19 treatment by Exscalate4CoV consortium, a multidisciplinary European center of excellence created with the aim to fighting coronavirus by combining the best supercomputing resources and artificial intelligence with state of the art experimental facilities up through clinical validation.

• New digital open tools for researches are now being developed with the support of the European High Performance Computing Joint Undertaking to further accelerate the drug discovery process.

MILAN, Italy, July 26, 2022 – Dompé farmaceutici S.p.A (“Dompé”) today announced positive results from two studies demonstrating that treatment with oral raloxifene, a selective estrogen receptor modulator (SERM) with a proven safety profile, may be effective against SARS-CoV-2, including its clinically relevant variants. The two studies were conducted in collaboration with the Italian National Institute for the Infectious Diseases “Lazzaro Spallanzani” in Rome and other important clinical and preclinical research groups highly committed to COVID-19 research. “The clinical results on raloxifene published on Lancet’s eClinical Medicine[1]show a significant virological impact in term of negative nasopharyngeal swab at day 7 in COVID-19 patients treated at home with raloxifene compared to standard of care. This randomized clinical trial confirm the in vitro data published in Nature’s Cell Death and Disease[2], on the efficacy of Raloxifene on cellular lines experimentally infected by SARS-CoV-2” said Emanuele Nicastri, author of both studies and Director of the Infectious and Tropical Diseases Unit of the Spallanzani Institute in Rome, where Italy’s very first Covid-19 patients were hospitalized.

Raloxifene was identified by the Exscalate4CoV[3] (E4C) project, a group composed of 30 public and private institutions from seven countries and funded by EU Commission’s in the frame of its Horizon 2020 Framework Programme[4], aimed at fighting Coronavirus with the latest European supercomputing resources and experimental facilities. Results were driven by the use of Exscalate, Dompé’s supercomputing platform which leveraged a database of 500 billion molecules to find those capable of targeting clinically relevant coronavirus variants. Due to its processing capacity of more than 3 million molecules per second, Exscalate is currently the most powerful intelligent supercomputing drug design platform. This processing power allowed the E4C researchers to rapidly select and repurpose a generic molecule with known efficacy and tolerability to make it available to the global community. As raloxifene is a generic molecule already tested and approvedfor the treatment of osteoporosis, this was a not for profit effortaimed at providing a globally available low cost treatment.

The first study on raloxifene, published in The Lancet’s eClinical Medicine, demonstrated that after seven days of treatment, patients taking raloxifene showed an improvement in symptoms compared to patients receiving placebo (please refer to www.clinialtrials.gov for additional clinical trial details). The second study, published in Cell Death and Disease), indicates raloxifene as a potential agent to treat mild-to-moderate COVID-19 caused by the most common SARS-CoV-2 variants. Mechanistic studies[5] confirmed the significant affinity of raloxifene for the Spike protein, as predicted by in silico studies. Researchers concluded that raloxifene is efficacious against the main SARS-CoV-2 variants and could represent a useful addition to the therapeutic arm for the management of Covid-19.

“Supercomputing is already demonstrating its potential for finding new solutions at previously unprecedented speeds in many domains, including medicine. I am very pleased that the Commission has supported the Exscalate4Cov consortium to discover promising treatments for COVID-19, and we now look forward to seeing the results of the consortium’s successor LIGATE project[6], which is developing a new drug discovery platform with the support of the European High Performance Computing Joint Undertaking” commented Thomas Skordas, Deputy Director-General of the European Commission’s Directorate-General for Communications Networks, Content and Technology (DG CONNECT).

“All of us at Dompé are incredibly proud of our contribution to the identification of new solutions to reduce the impact of COVID-19 on patients, healthcare systems, and their communities” said Marcello Allegretti, Chief Scientific Officer at Dompé. “The huge power of our unique supercomputing platform has been a gamechanger, but we want to thank all patients and researchers around the world who participated in these two studies. These results show the importance of combining pharmacological knowledge and breakthrough technologies as AI tools, to exploit the potential of repurposed drugs, and to elevate understanding of yet to be revealed mechanisms of action to address critically unmet medical needs".

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About Raloxifene
Raloxifene is currently on the market for the treatment of osteoporosis and is well-tolerated with a known safety profile. The compound is a marketed drug and has been approved by the EMA for clinical use.

About Dompé
Dompé is a private, rapidly scaling international biopharmaceutical company founded in Milan, Italy, with a 130-year legacy of medical innovation. The R&D department of the company is leveraging EXSCALATE, a structure-based virtual screening platform developed in-house and presently one of the most powerful supercomputing and artificial intelligence platforms. Today, Dompé employs more than 800 employees worldwide and maintains a U.S. commercial operations hub in the San Francisco Bay Area as well as an R&D presence in Boston.

Forward Looking Statements
This press release refers to certain information that may not coincide with expected future results. Dompé firmly believes in the soundness and reasonableness of the concepts expressed. However, some of the information is subject to a certain degree of indetermination in relation to its research and development activities and the necessary verifications to be performed by regulatory bodies. Therefore, as of today, Dompé cannot guarantee that the expected results will be consistent with the information provided above.

References

[1] A phase 2 randomized, double-blinded, placebocontrolled, multicenter trial evaluating the efficacy and safety of raloxifene for patients with mild to moderate COVID-19 - https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(22)00180-8/fulltext

[2] “Characterization of raloxifene as a potential pharmacological agent against SARS-CoV-2 and its variants” in Nature Cell Death and Disease (https://doi.org/10.1038/s41419-022-04961-z).

[3] The Exscalate4Cov (www.exscalate4cov.eu) consortium, supported by the the EU’s Horizon 2020 programme for research and innovation, was coordinated by Dompé farmaceutici, and composed by 18 member institutions from seven European countries: Politecnico di Milano (Dept. of Electronics, Information and Bioengineering), Consorzio Interuniversitario CINECA(Supercomputing Innovation and Applications), Università degli Studi di Milano (Department of Pharmaceutical Sciences), International Institute of Molecular and Cell Biology in Warsaw (Warsaw, Poland), KU Leuven, Elettra Sincrotrone Trieste, Fraunhofer Institute for Molecular Biology and Applied Ecology, BSC Barcelona Supercomputing Centre, Forschungszentrum Jülich, Università Federico II di Napoli, Università degli Studi di Cagliari, SIB Swiss Institute of Bioinformatics, KTH Royal Institute of Technology (Department of Applied Physics), Associazione Big Data, Istituto Nazionale di Fisica Nucleare (INFN), Istituto nazionale per le malattie infettive Lazzaro Spallanzani and Chelonia Applied Science. Part of E4C League were: ENI, SAS, Alfasigma, CFEL Center for Free-Electron Laser Science, MMV Medicines for Malaria Ventures, Esteve Pharmaceutical, University of Basel Biozentrum, University of Basel Innovation Office, University of Basel Department of Pharmaceutical Sciences, D-wave, Pierre fabre, Greenpharma, University of Sheffield - Sheffield Institute for Translational Neuroscience – SITraN, Dassault Systemes- Biovia, Institute of Food Science Research, CECAM Centre Européen de Calcul Atomique et Moleculaire, Nanome, Esteco, IT4Innovation, Università degli Studi della Tuscia, Sofia University “St. Kl. Ohridski”, Faculty of Physics, Institut Cochin.

[4]EXaSCale smArt pLatform Against paThogEns for Corona Virus / Grant agreement ID: 101003551 https://cordis.europa.eu/project/id/101003551

[5] “Repurposing the estrogen receptor modulator raloxifene to treat SARS-CoV-2 infection” in Nature Cell Death & Differentiation journal (https://www.nature.com/articles/s41418-021-00844-6) and “Characterization of raloxifene as a potential pharmacological agent against SARS-CoV-2 and its variants” in Nature Cell Death and Disease (https://doi.org/10.1038/s41419-022-04961-z).

[6]https://www.ligateproject.eu/