Philochem AG

Novel ultra-high affinity ligand OncoFAP targets Fibroblast Activation Protein (FAP), associated with a variety of solid tumorsLicensing agreement between Philochem and Blue Earth Diagnostics, one of the Bracco family of companies, encompasses applications of OncoFAP for diagnostic and medical imagingPhilogen’s Phase I clinical trial with investigational 68Ga-OncoFAP is underway in Europe, with first three patients successfully imaged Blue Earth Diagnostics will assume further clinical development and future commercialization activities of OncoFAP for diagnostic or medical imaging purposes worldwide ZURICH, Switzerland and OXFORD, United Kingdom and MONROE TOWNSHIP, N.J., Dec. 04, 2023 (GLOBE NEWSWIRE) -- Philochem AG, a wholly owned subsidiary of Philogen S.p.A., and Blue Earth Diagnostics, a Bracco company and recognized leader in the development and commercialization of innovative PET radiopharmaceuticals, today provided additional information regarding a March 2022 licensing and collaboration agreement between Philochem and Blue Earth Diagnostics. The collaboration encompasses the development of OncoFAP, a proprietary, small organic ligand with ultra-high affinity to Fibroblast Activation Protein (FAP), for applications in the diagnostic imaging of solid tumors. Under the agreement, the Philogen Group is conducting a Phase 1 clinical study to evaluate the safety and dosimetry of 68Ga-OncoFAP (68Ga-OncoFAP-DOTAGA) in patients with solid tumors. The agreement provides Blue Earth Diagnostics rights to develop and commercialize 68Ga-OncoFAP worldwide. FAP is a tumor-associated antigen which is expressed in more than 90% of epithelial cancers (e.g., malignant breast, colorectal, ovarian, lung, skin, prostate, and pancreatic cancers, as well as in some soft tissue and bone sarcomas). The Philogen Group has a Phase I clinical trial (called FAPrimo) underway in Europe to evaluate the safety and dosimetry of 68Ga-OncoFAP in patients with solid tumors. The study is planned to enroll up to 20 patients who will undergo PET/CT imaging with 68Ga-OncoFAP. The first three enrolled patients in the trial were imaged in November 2023 at the National Cancer Institute of Milan (INT). To date, 68Ga-OncoFAP-DOTAGA has been used for PET imaging applications in approximately 100 patients with various solid tumors through Philochem’s collaboration with the University of Münster, Germany. Prof. Dr. Dario Neri, Member of the Board of Philochem and CEO of the Philogen Group, commented: “We are excited about the promising tumor-targeting performance of 68Ga-OncoFAP in preclinical models and human patients to date. Philochem discovered and published the first paper on this important tumor targeting ligand in 2021. We believe OncoFAP technology has potential to pave the way for a new approach to tumor diagnosis, and significantly improve diagnosis and informed management for patients who have solid tumor cancers.” “We are delighted to announce this key milestone of the first three patients being dosed in the Phase 1 trial for 68Ga-OncoFAP PET in the detection and localization of advanced solid tumors,” commented David Gauden, D. Phil., Chief Executive Officer of Blue Earth Diagnostics. “68Ga-OncoFAP is an innovative and promising addition to Blue Earth Diagnostics’ robust portfolio of precision PET radiopharmaceuticals. We are grateful for the support of our parent company, Bracco Imaging, S.p.A., in helping to advance innovation to shape the future of precision medicine and improve patients’ lives worldwide with imaging technology such as OncoFAP. Based on preclinical studies and early clinical experience, 68Ga-OncoFAP has demonstrated favorable radiochemical properties, rapid clearance from organs and soft tissues and avid tumor uptake. We look forward to continuing collaboration with Philochem throughout this Phase 1 trial and applying our deep expertise in radiopharmaceutical development and commercialization as we advance further, with the goal to help patients and address unmet needs in cancer.” About Fibroblast Activation Protein (FAP) and FAP-targeted TechnologyFibroblast Activation Protein, or FAP, is a transmembrane protein that is overexpressed in cancer-associated-fibroblasts (CAFs) in the tumor microenvironment of most tumor types, but expressed at low levels in normal adult tissues. It is involved in a variety of tumor-promoting activities and is considered a promising target with diagnostic and theranostic potential in a variety of diseases. FAP is being investigated for use in diagnostic imaging and therapy in multiple tumor types, such as colon, breast, lung, pancreatic and esophageal cancers, among others. CAFs are also highly expressed in tissue remodeling, and FAP imaging may have applications in benign fibrotic conditions such as wound healing, as well as in chronic inflammation, cirrhosis, and cardiovascular and rheumatoid diseases.Radiolabeled FAP ligands have demonstrated high binding affinity, rapid binding to FAP-expressing tumors and impressive lesion to background ratios in patients with a broad range of cancer types. They can be labeled with isotopes such as 68Ga or 18F for diagnostic PET imaging, or with therapeutic radioisotopes such as 177Lu or 225Ac for therapy. About Philochem and the Philogen GroupPhilochem is a fully owned subsidiary of the Philogen Group, a Swiss-Italian, clinical-stage biotechnology company listed on the Italian Stock Exchange. Philogen is engaged in the discovery and development of novel pharmaceutical and biopharmaceutical products. Philogen’s strategy is to selectively deliver bioactive agents (such as radionuclides, cytokines or drugs) to the site of disease using antibodies or small organic ligands. This technology has generated a strong proprietary pipeline of clinical-stage products and preclinical compounds in an array of disease indications. Philogen is headquartered in Siena, Italy, and has research activities at its subsidiary company Philochem near Zurich, Switzerland. Philogen has signed agreements with several major pharmaceutical companies. For more information, please visit www.philogen.com and www.philochem.com. About Blue Earth DiagnosticsBlue Earth Diagnostics, an indirect subsidiary of Bracco Imaging S.p.A., is a growing international molecular imaging company focused on delivering innovative, well-differentiated diagnostic solutions that inform patient care. Formed in 2014, the Company’s success is driven by its management expertise and supported by a demonstrated track record of rapid development and commercialization of positron emission tomography (PET) radiopharmaceuticals. Blue Earth Diagnostics’ expanding oncology portfolio encompasses a variety of disease states, including prostate cancer and neuro-oncology. Blue Earth Diagnostics is committed to the timely development and commercialization of precision radiopharmaceuticals for potential use in imaging and therapy. For more information, please visit: www.blueearthdiagnostics.com. About Bracco Imaging Bracco Imaging S.p.A., part of the Bracco Group, is a world-leading diagnostic imaging provider. Headquartered in Milan, Italy, Bracco Imaging develops, manufactures and markets diagnostic imaging agents and solutions. It offers a product and solution portfolio for all key diagnostic imaging modalities: X-ray imaging (including Computed Tomography-CT, Interventional Radiology, and Cardiac Catheterization), Magnetic Resonance Imaging (MRI), Contrast Enhanced Ultrasound (CEUS), and Nuclear Medicine through radioactive tracers and novel PET imaging agents to inform clinical management and guide care for cancer patients in areas of unmet medical need. Our continually evolving portfolio is completed by a range of medical devices, advanced administration systems and dose-management software. In 2019 Bracco Imaging enriched its product portfolio by expanding the range of oncology nuclear imaging solutions in the urology segment and other specialties with the acquisition of Blue Earth Diagnostics. In 2021, Bracco Imaging established Blue Earth Therapeutics as a separate, cutting-edge biotechnology vehicle to develop radiopharmaceutical therapies. Visit: www.braccoimaging.com. Contacts: For Philogen Dr. Emanuele Puca Investor Relations+41 (0) 43 544 88 00 emanuele.puca@philogen.com For Blue Earth Diagnostics (U.S.)Priscilla HarlanVice President, Corporate Communications(M) (781) 799-7917priscilla.harlan@blueearthdx.com For Blue Earth Diagnostics (UK) Clare GidleyAssociate Director Marketing and CommunicationsTel: +44 (0) 7917 536939clare.gidley@blueearthdx.com MediaSam Brown Inc.Mike Beyer(M) (312) 961-2502mikebeyer@sambrown.com PP-UK-0674 Date of preparation: November 2023

Philogen Announces Publication of a New Study in Collaboration with Google focused on Machine Learning models applied to DNA-Encoded Chemical Library Technology The collaboration has focused on the use of Google’s Machine Learning models combined with Philochem’s DNA-Encoded Chemical Libraries The research activity promises to have a direct impact on the discovery of novel tumor-targeting small organic ligands with broad applicability in a number of different indications Siena, Italy, March 28, 2023 - Philogen S.p.A., a clinical-stage biotechnology company focused on the development of innovative antibody and small molecule ligands, announces the publication of a new study conducted in collaboration with Google focused on the use of Machine Learning models applied to the screening of DNA-Encoded Chemical Libraries (DELs). Philogen practices DEL technology within its fully-owned Swiss-based Philochem AG subsidiary. DELs emerged as an efficient and cost-effective ligand discovery tool. The technology allows the rapid selection of specific binders (“Phenotype”), physically connected to unique DNA tags (“Genotype”) that work as amplifiable identification barcodes. Philochem has synthesized several DNA-Encoded Chemical Libraries, featuring different designs, that have yielded high affinity and selective binders to a variety of target proteins of pharmaceutical interest. Results of DEL selection are extremely data-rich, as they may contain enrichment information for billions of compounds on a variety of different targets. In principle, this information can be exploited using computational methods both for the affinity maturation of DEL-derived HIT compounds and for the characterization of binding specificities. In this collaborative project, Google and Philochem, a fully-owned subsidiary of Philogen, have applied DEL Technology and Instance-Level Deep Learning Modelling to identify tumor-targeting ligands against Carbonic Anhydrase IX (CAIX), a clinically validated marker of hypoxia and of clear cell Renal Cell Carcinoma. The approach yielded binders that showed accumulation on the surface of CAIX-expressing tumor cells in cellular binding assays. The best compound displayed a binding affinity of 5.7 nM and showed preferential tumor accumulation in in vivo pre-clinical models of Renal Cell Carcinoma. The successful translation of LEAD candidates for in vivo tumor-targeting applications demonstrates the potential of using machine learning with DEL Technology to advance real world drug discovery. The results of the study are available as preprint on the BioRXiv website at www.biorxiv.org/content/10.1101/2023.01.25.525453v1. Dario Neri, Chief Executive Officer of Philogen commented: “We are excited by the potential of the synergy between DNA-Encoded Chemical Libraries and Artificial Intelligence. The powerful discovery approach that we have developed together with Google should be broadly applicable to additional targets of pharmaceutical interest for the discovery of novel drug prototypes.” Philogen Group Description Philogen is an Italian-Swiss company active in the biotechnology sector, specialized in the research and development of pharmaceutical products for the treatment of highly lethal diseases. The Group focuses on the discovery and development of targeted anticancer drugs, exploiting high-affinity ligands for tumor markers (also called tumor antigens). These ligands - human monoclonal antibodies or small organic molecules - are identified using Antibody Phage Display Libraries and DNA-Encoded Chemical Library technologies. The Group's main therapeutic strategy for the treatment of these diseases is represented by the concept of tumor targeting. This approach is based on the use of ligands capable of selectively delivering very potent therapeutic active ingredients (such as pro-inflammatory cytokines) to the tumor mass, sparing healthy tissues. Over the years, Philogen has mainly developed monoclonal antibody-based ligands that are specific for antigens expressed in tumor-associated blood vessels, but not expressed in blood vessels associated with healthy tissues. These antigens are usually more abundant, more stable and better accessible than those expressed directly on the surface of tumor cells. The elaborate expertise in the field of vascular targeting enabled the generation of a strong portfolio with many ongoing projects which are currently pursued by the Group. The Group's objective is to generate, develop and market innovative products for the treatment of diseases for which medical science has not yet identified satisfactory therapies. This is achieved by exploiting (i) proprietary technologies for the isolation of ligands that react with antigens present in certain diseases, (ii) experience in the development of products which selectively accumulate at the disease sites, (iii) experience in drug manufacturing and development, and (iv) an extensive portfolio of patents and intellectual property rights. Although the Group's drugs are primarily oncology applications, the targeting approach is also potentially applicable to other diseases, such as certain chronic inflammatory diseases. FOR MORE INFORMATION: Philogen - Investor Relations IR@philogen.com - Emanuele Puca | Investor Relations Consilium Strategic Communications contacts Mary-Jane Elliott, Davide Salvi Philogen@consilium-comms.com

Collaboration allows Philochem to secure access to 177Lutetium N.C.A., a medical isotope used in multiple clinical trials for radiopharmaceutical therapies in areas of high unmet medical needs and CMO manufacturing for lead candidate OTELFINGEN, Switzerland, SEIBERSDORF, Austria and PETAH TIKVA, Israel, Dec. 13, 2022 /PRNewswire/ -- Philochem, Seibersdorf Laboratories and Isotopia Molecular Imaging have today announced that they have signed agreements that will help advance the next generation of Radiopharmaceutical Therapies for cancer treatment. Under these agreements, Isotopia will supply high quality 177 Lu-n.c.a to Seibersdorf Laboratories for the purpose of conducting development and manufacturing activities for Philochem's proprietary therapeutic candidate, OncoFAP-23. OncoFAP-23 is a novel small molecule ligand developed for Targeted Radionuclide Therapy which selectively binds to Fibroblast Activation Protein (FAP), an antigen expressed in a variety of solid human malignancies, while being undetectable in most healthy tissues. Philochem's scientists demonstrated that 177Lu-OncoFAP-23 exhibits, in pre-clinical models, a very high and selective tumor uptake and with a significantly extended residence time at the site of disease, compared to other 177Lu-FAP-ligands. 177Lu n.c.a is used in Targeted Radionuclide Therapy in the field of Precision Medicine in Oncology. By binding n.c.a. 177Lu isotopes to tumor-specific targeting molecules, the resulting radiopharmaceutical targets the tumor and delivers precise cell-killing radiation that spares normal healthy tissue. Isotopia has developed a reliable and unique GMP method to produce a highly pure form of 177Lu. 177Lu n.c.a contains no Mercury (Hg) and no metastable 177Lu-m, therefore there is no need for cost intensive clinical waste management. Seibersdorf's CEO, Martina Schwaiger stated: "The new agreement is a great opportunity for our team and we are pleased to be working with Philochem and Isotopia Molecular Imaging on this important sector of medical care." Sammuele Cazzamalli, PhD, Head of Small Molecule Therapeutics at Philochem commented: " We are delighted to start working with Isotopia and Seibersdorf Laboratories on the manufacturing of our Targeted Radioligand Therapeutics. This collaboration is important to pursue Philochem's bench-to-bedside translational research, with competitive timelines, on our novel best-in-class 177Lu-OncoFAP-23." "This three-way collaboration demonstrates the ability to provide the full support for clinical development" stated Keren Moshkoviz, Director of Business Development at Isotopia. "Isotopia's aim is to play a significant role in early developments that will benefit patients in the future. We try to build a platform that can drive new products into the clinic in a simple and agile way. We are excited to work with the Philochem and Seibersdorf Laboratories team to bring this product to the clinic ." About Philochem and the Philogen Group Philochem is a fully owned subsidiary of the Philogen Group, a Swiss-Italian clinical-stage biotechnology company listed on the Italian Stock Exchange. Philogen is engaged in the discovery and development of novel pharmaceutical and biopharmaceutical products. Philogen's strategy is to selectively deliver bioactive agents (such as radionuclides, cytokines, or drugs) to the site of disease using antibodies or small organic ligands. This technology has generated a strong proprietary pipeline of clinical-stage products and preclinical compounds in an array of disease indications. Philogen is headquartered in Siena, Italy, and has research activities at its subsidiary company Philochem near Zurich, Switzerland. Philogen has signed agreements with several major pharmaceutical companies. Contact: Emanuele Puca \ Investor Relations Tel: +41 (0) 43 544 88 00 Email: [email protected] \ About Isotopia Isotopia Molecular Imaging Ltd. is a dominant 177Lu n.c.a supplier, its development team is a multidisciplinary team consisting of nuclear pharmacists, radiochemists, nuclear engineers, and physicists. The experienced Isotopia team, together with its nuclear pharmacy, cyclotron facility, 177Lu production site and sterile manufacturing plant, are a well-established platform for manufacturing and collaborations. Isotopia creates collaborations between the scientific and medical community to further develop and experiment with new markers for imaging applications and molecular therapy. Contact: Keren Moshkoviz Tel: +972 (54) 8182398 Email: [email protected] About Seibersdorf Labor GmbH (Seibersdorf Laboratories) Seibersdorf Labor GmbH is an Austrian company specialized in high quality laboratory and analysis work, application-oriented research and development as well as consulting and training. The teams of Seibersdorf Laboratories are service, know-how and technology provider and cover a broad area of scientific expertise: development, production and quality control of radiopharmaceuticals, anti-doping and forensic analysis, radiation protection, ionizing and non-ionizing radiation, radio frequency engineering and electromagnetic compatibility. The experts of Seibersdorf Laboratories represent Austria on various international committees. Contact: Roland Müller \ Head Pharmaceuticals Tel: +43 50 550 3470 Email: [email protected] SOURCE Isotopia; Philochem AG; Seibersdorf Labor GmbH