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A new test to help detect and monitor cancers ​«We are bringing a new diagnostic solution to improve cancer detection and management throughout the patient care pathway.» A simple and accessible test Our R&D team found that hPG80 protein was present at high levels in the blood of patients with 16 different types of cancer, regardless of the stage of the disease.​ ​ Building on this groundbreaking French research, we developed a practical and cost-effective blood test: DxPG80.Lab. DxPG80.Lab: a new device to lead the fight against cancer Through a simple blood test, the DxPG80.Lab test detects the presence of hPG 80 , a biomarker associated with cancer activity. Commercialized with CE marking​ View product Easy Rapid execution (<3 hours) Reliability Affordable CE-marked hPG80 is detected in all cancers tested, including those for which no markers are available. Tested on > 4,000 cancer patients and 1,200 healthy subjects​. Detected across all stages of 16 different types of cancer​. View Clinical Data Proposing a more efficient support A biomarker to support decision-making throughout the patient care pathway.​​​​​​​ DxPG80.Lab provides valuable insights to help clinicians optimise patient care. DETECTION DIAGNOSIS PROGNOSIS TREATMENT OUTCOME PREDICTION TREATMENT MONITORING/ FOLLOW-UP Despite significant progress over the last decade, the burden of cancer continues to rise. 20 million new cases per year, expected to rise to 31M in 2040. > 50% late diagnosis Over half of cancers in the US are diagnosed at stages III and IV​. 79% vs 11% 79% vs 11% mortality 5-year cancer​ s pecific mortality when diagnosed late vs early stage​. Sources: WHO and Cancer Atlas Strong unmet medical need To detect cancer earlier and monitor treatment with a low-cost blood test. It's time to take concrete action

Prognostic Value of Plasma hPG80 (Circulating Progastrin) in Metastatic Renal Cell Carcinoma Jan, 2021 + Journals - Cancers - Volume 13 - Issue 3 - 10.3390/cancers13030375 Abstract Precise management of kidney cancer requires the identification of prognostic factors. hPG80 (circulating progastrin) is a tumor promoting peptide present in the blood of patients with various cancers, including renal cell carcinoma (RCC). In this study, we evaluated the prognostic value of plasma hPG80 in 143 prospectively collected patients with metastatic RCC (mRCC). The prognostic impact of hPG80 levels on overall survival (OS) in mRCC patients after controlling for hPG80 levels in non-cancer age matched controls was determined and compared to the International Metastatic Database Consortium (IMDC) risk model (good, intermediate, poor). ROC curves were used to evaluate the diagnostic accuracy of hPG80 using the area under the curve (AUC). Our results showed that plasma hPG80 was detected in 94% of mRCC patients. hPG80 levels displayed high predictive accuracy with an AUC of 0.93 and 0.84 when compared to 18–25 year old controls and 50–80 year old controls, respectively. mRCC patients with high hPG80 levels (>4.5 pM) had significantly lower OS compared to patients with low hPG80 levels (<4.5 pM) (12 versus 31.2 months, respectively; p = 0.0031). Adding hPG80 levels (score of 1 for patients having hPG80 levels > 4.5 pM) to the six variables of the IMDC risk model showed a greater and significant difference in OS between the newly defined good-, intermediate- and poor-risk groups (p = 0.0003 compared to p = 0.0076). Finally, when patients with IMDC intermediate-risk group were further divided into two groups based on hPG80 levels within these subgroups, increased OS were observed in patients with low hPG80 levels (<4.5 pM). In conclusion, our data suggest that hPG80 could be used for prognosticating survival in mRCC alone or integrated to the IMDC score (by adding a variable to the IMDC score or by substratifying the IMDC risk groups), be a prognostic biomarker in mRCC patients. Manish Kohli 1,*, Winston Tan 2, Bérengère Vire 3, Pierre Liaud 3, Mélina Blairvacq 3, Frederic Berthier 4, Daniel Rouison 4, George Garnier 4, Léa Payen 5, Thierry Cousin 6, Dominique Joubert 6 and Alexandre Prieur 6,*

hPG 80 : a new blood biomarker What is hPG80 ? Progastrin is an intracellular protein that is, or not, maturated into gastrin. Non-Pathological Condition Progastrin is not detected in the blood of healthy subjects. Pathological Condition hPG80 (circulating progastrin) is detected in the blood of cancer patients. The ROCHE laboratory markets a test for the detection of Progastrin-releasing peptide (Pro-GRP) to differentiate between 2 types of lung cancer. hPG80 (Progastrin) and Progastrin-releasing peptide (Pro-GRP) are two completely different proteins even though they share the word "Progastrin / Pro-Gastrin” with the same phonetics. hPG80 : a biomarker significantly higher in the blood of cancer patients Meta-analysis of all retrospective and prospective studies, published and unpublished data. ​​ N=4,085 patients with cancers & N=1,199 healthy subjects. View Clinical Data Adapted from You et al, 2020; Kholi et al, 2021; Chauhan et al, 2022; Dupuy et al, 2022, Prieur et al, 2023; Doucet et al, 2023, You et al, 2023 and Hofman et al, 2023 and unpublished data hPG80: a biomarker of cancer activity Tumoral mass Peripheral tissue The biomarker hPG80 is detectable in the tumor/bloodstream of cancer patients at every stage of tumor progression, from the primary tumor to metastasis. This figure illustrates the high expression of hPG 80 by tumor cells from pancreatic and liver cancer (A) and (B), respectively. The tissues peripheral to the tumor masses were devoid of hPG 80 -immunoreactive cells (C) and (D). Scale bars: 25 µm. Immunomarking of cancer biopsy hPG 80 : red, Heparan sulfates: green, Cell nuclei: blue You et al. EBioMedicine 2020 Close link between Wnt pathway, Cancer and hPG80 The Wnt signaling pathway is dysregulated in cancer. Zhong et al, Cancer Metastatic review (2020) The Wnt signaling pathway regulates a wide range of cellular functions during development and adulthood, including cell proliferation, cell fate determination, apoptosis, cell migration and cell polarity during development and stem cell maintenance in adults. ​ It is dysregulated in most cancers. ​ It plays a important role in the development of cancer and is involved in key features of cancer. The GAST gene and progastrin are overexpressed via the Wnt oncogenic pathway. The GAST gene, which encodes progastrin, is a target of the Wnt/ß-catenin/ Tcf4 oncogenic pathway. ​ GAST and consequently hPG80 are overexpressed in tumor tissues. ​​ Once secreted, hPG80 will trigger a positive feedback loop that will activate the Wnt signaling pathway, further amplifying hPG80 secretion. Joubert et al, under submission hPG 80 is a pro-oncogenic factor. It has been shown that hPG80 plays a major role in tumor promotion and progression: Pro-angiogenic factor Anti-apoptotic factor Regulation of cell-cell junctions Cancer stem cells survival ​ hPG80 neutralization: Inhibits Wnt-dependent tumorigenicity in vivo. Induces differentiation of cancer cells and then their death by apoptosis. Reduces tumor neovascularization in xenograft cells in nude mice. Joubert et al, under submission

hPG80 (Circulating Progastrin), a Novel Blood-Based Biomarker for Detection of Poorly Differentiated Neuroendocrine Carcinoma and Well Differentiated Neuroendocrine Tumors February 2022 + Journals - Cancers 2022, 14, 863 Simple Summary Current blood-based biomarkers for neuroendocrine neoplasms (NENs) lack both sensitivity and specificity. Human circulating progastrin (hPG80) can be easily measured in plasma by ELISA. This study is the first to examine hPG80 in NENs. The study demonstrated increased levels of hPG80 in all sub-types of NENs, with a high sensitivity and specificity demonstrated. Plasma hPG80 in NENs may be a diagnostic blood biomarker for both low- and high-grade NENs; further study is warranted. A prospective multi-center trial is ongoing in NET to evaluate hPG80 as a means of monitoring disease (NCT04750954). Abstract Current blood-based biomarkers for neuroendocrine neoplasms (NENs) lack both sensitivity and specificity. Human circulating progastrin (hPG80) is a novel biomarker that can be easily measured in plasma by ELISA. This study is the first to examine hPG80 in NENs. Plasma hPG80 was quantified from 95 stage IV NEN patients, using DxPG80technology (ECS Progastrin, Switzerland) and compared with hPG80 concentrations in two cohorts of healthy donor controls aged 50–80 (n = 252) and 18–25 (n = 137). Median hPG80 in NENs patients was 5.54 pM compared to 1.5 pM for the 50–80 controls and 0.29 pM the 18–25 cohort (p < 0.0001). Subgroup analysis revealed median hPG80 levels significantly higher than for either control cohort in neuroendocrine carcinoma (NEC; n = 25) and neuroendocrine tumors (NET; n = 70) including the small-cell lung cancer (SCLC) sub-cohort (n = 13). Diagnostic accuracy, estimated by AUCs, was high for NENs, as well as both sub-groups (NEC/NET) when compared to the younger and older control groups. Plasma hPG80 in NENs may be a diagnostic blood biomarker for both low- and high-grade NENs; further study is warranted. A prospective multi-center trial is ongoing in NET to evaluate hPG80 as a means of monitoring disease (NCT04750954). Aman Chauhan, Alexandre Prieur, Jill Kolesar, Susanne Arnold, Léa Payen, Younes Mahi, Berengere Vire, Madison Sands, B. Mark Evers, Dominique Joubert and Lowell Anthony.

The oncogenic and druggable hPG80 (Progastrin) is overexpressed in multiple cancers and detected in the blood of patients Dec, 2019 + RESEARCH PAPER Volume 5, 1102574, Research in context Evidence before study The National Cancer Institute recently highlighted the need forbiomarkers to improve early detection of cancers, monitor treatment effects and detect disease relapses. Therefore, the identification of a new tumor blood-based marker with broad expression across tumor types might have a significant impact on diagnostic and follow-up of patients. hPG80 (progastrin) was shown to be over-expressed in human colorectal tumor cells. Interestingly, GAST is a direct target of the Wnt/ß-catenin/Tcf4 oncogenic pathway. Since this pathway is activated inmany other cancers and plays a major function in cancer stem cells survival, we hypothesized that hPG80 (i) might be expressed by other types of cancers, and would be present in the blood of patients with tumors different from colorectal cancers and (ii) might be a drug target for various type of cancers. ​ Added value of this study Here we show that hPG80 is expressed by the tumor and present in the blood of 11 different types of cancer patients. Two retrospective kinetic studies where blood samples were collected regularly from cancer patients undergoing different treatments revealed strong associations between longitudinal hPG80 concentrations and anti-cancer treatment efficacy. We provide data showing the decrease of hPG80 after surgery in a cohort of patients with peritoneal involvements from gastroin-testinal cancers, treated with peri-operative chemotherapy regimens and cytoreductive surgery. We also show the correlationbetween hPG80 levels and standard imaging in a cohort of patients with hepatocellular carcinoma, managed with local or systemic treatments, including patients with no detectable levels of alpha-fetoprotein. Finally, we show that targeting hPG80 with our humanized antibody decreases self-renewal capacity of cancer stem cells from various origins. ​ Implications of all available evidence The technology we developed to detect hPG80 in the blood isr obust, reliable and inexpensive, making this test easy to implement by oncologists. This technology could be used to improve early cancer diagnosis and treatment efficacy monitoring. Furthermore, in this study we show that our anti-hPG80 therapeutic antibody, that was initially found to target the Wnt pathway and decrease self-renewal capacity in cancer stem cells from colorectal cancer, is envisioned to have the same effect on tumors from other origins.

​ A novel method to detect hPG80 (human circulating progastrin) in the blood Sep, 2021 + Journals - Analytical Methods - 2021, 13, 4468 – 4477 Abstract hPG80 (human circulating progastrin) is produced and released by cancer cells. We recently reported that hPG80 is detected in the blood of patients with cancers from different origins, suggesting its potential utility for cancer detection. To accurately measure hPG80 in the blood of patients, we developed the DxPG80 test, a sandwich Enzyme-Linked Immunosorbent Assay (ELISA). This test quantifies hPG80 in EDTA plasma samples. The analytical performances of the DxPG80 test were evaluated using standard procedures and guidelines specific to ELISA technology. We showed high specificity for hPG80 with no cross-reactivity with human glycine-extended gastrin (hG17-Gly), human carboxy-amidated gastrin (hG17-NH2) or the CTFP (C-Terminus Flanking Peptide) and no interference with various endogenous or exogenous compounds. The test is linear between 0 and 50 pM hPG80 (native or recombinant). We demonstrated a trueness of measurement, an accuracy and a variability of hPG80 quantification with the DxPG80 test below the 20% relative errors as recommended in the guidelines. The limit of detection of hPG80and the limit of quantification were calculated as 1 pM and 3.3 pM respectively. In conclusion, these results show the strong analytical performance of the DxPG80 test to measure hPG80 in blood samples. Cappellini Monica, Flaceliere Maud, Saywell Veronique, Soule Julien, Blanc Emilie, Belouin Fanny, Ortiz Erika, Canterel-Thouennon Lucile, Poupeau Sophie, Tigrett Sylvia, Vire Bérengère, Liaud Pierre, Blairvacq Mélina, Joubert Dominique, Prieur Alexandre

Plasma hPG80 (Circulating Progastrin) as a Novel Prognostic Biomarker for Hepatocellular Carcinoma Jan, 2022 + Journals - Cancers 2022, 14(2), 402 Abstract Alpha-fetoprotein (AFP) is the most widely used biomarker for hepatocellular carcinoma (HCC) prognosis. However, AFP is not useful in establishing a prognosis for patients with a tumor in the early stages. hPG80 (circulating progastrin) is a tumor promoting peptide present in the blood of patients with various cancers, including HCC. In this study, we evaluated the prognostic value of plasma hPG80 in patients with HCC, alone or in combination with AFP. A total of 168 HCC patients were tested prospectively for hPG80 and analyzed retrospectively. The prognostic impact of hPG80 and AFP levels on patient survival was assessed using Kaplan-Meier curves and log-rank tests. hPG80 was detected in 84% of HCC patients. There was no correlation between hPG80 and AFP levels in the training and validation cohorts. Both cohorts showed higher sensitivity of hPG80 compared to AFP, especially at early stages. Patients with high hPG80(hPG80+) levels (optimal cutoff value 4.5 pM) had significantly lower median overall survival (OS) compared to patients with low hPG80 (hPG80−) levels (12.4 months versus not reached respectively, p < 0.0001). Further stratification by combining hPG80 and AFP levels (cutoff 100 ng/mL) improved prognosis in particular for those patients with low AFP level (hPG80−/AFP+ and hPG80−/AFP−, 13.4 months versus not reached respectively, p < 0.0001 and hPG80+/AFP+ and hPG80+/AFP−, 5.7 versus 26 months respectively, p < 0.0001). This was corroborated when analyses were performed using the BCLC staging especially at early stages. Our findings show that hPG80 could serve as a new prognostic biomarker in HCC. Used in combination with AFP, it improves the stratification of the patients in good and poor prognosis, especially for those patients with negative AFP and early-stage HCC. Marie Dupuy, Sarah Iltache, Benjamin Rivière, Alexandre Prieur, George Philippe Pageaux, José Ursic Bedoya, Stéphanie Faure, Heloïse Guillaumée and Eric Assenat.

About Us Our Mission In the battle against cancer, BIODENA CARE considers its mission as a succession of relays between Fundamental Scientific Knowledge on the one hand and "the Art and Science of Medicine" on the other. The final relay, undoubtedly the most important, is the one that the Physician must carry out alone with his Patient, against the disease. This is why, in order to never forget the Patient, we carry out our mission by exclusively serving Physicians with a single objective: « To ensure that demonstrations of basic science become effective, reliable and accessible solutions, handed over to physicians for the benefit of their patients. » Executive Team Philippe Pourquier CEO Skills AgroParisTech - Institut des Sciences et Industries du Vivant et de l'Environnement Bachelor of Engineering (B.E.), Microbiology and Genetics of Microorganisms Professional strength ​More than 38 years of professional experience in the field of in vitro diagnostics. Founder and Chief Executive Officer of Innovative Diagnotics, company who develops and produces ELISA and PCR reagents for the diagnosis of infectious zoonotic and veterinary diseases. ID employs over 170 staff members in its 5000 m² headquarters in Montpellier, France. Chief Executive Officer of AFYIA Diagnostics, it aims to provide easy-to-use and affordable multiplex diagnostics for human syndromic infectious diseases. Chief Executive Officer of ADELIS Technologies, a company developing an ultrasensitve and easy-to-use automat for size profiling of circulating DNA.​​​​ Nassima Mimoun Managing Director Skills Medical Doctor MBA from an international Business school in Paris ESCP Business School Harvard Business School: Executive Leadership Program Professional strength 25 years of experience in Pharma Industry. Broad range of experiences across various therapeutic areas at regional and local level in multiple markets and mainly in oncology. Solid experience in launching and successfully commercializing innovative products and identifying life cycle management opportunities. Ability to work successfully with external stakeholders by integrating their insights. Strong learning agility and a good track record in coming into new and challenging situations in both, strategic and operational roles using strong communication and interpersonal skills. Diversity & Inclusion as a DNA to build right teams and talents working cross functionally. Acting & leading by example. Supporting and driving transformations with flexibility and adaptability. Alix De Jacquelot Director of Business Development and Medical Partnerships Skills PharmD Specialized in health product development Professional strength 15 years' experience in pharmaceutical industry, including over 10 years in medical affairs, at regional, national and international levels. Cross-functional collaboration to ensure pre-launch and launch of innovative drugs in various therapeutic areas, including immuno-oncology. Good knowledge of clinical research, regulatory issues and market access. Strategic vision, field experience, good listening and analytical skills. Alexandre Prieur Chief Scientific Officer Skills Scientific Director since 2012 20 years in cancer research 8 years of R&D specific to hPG80 (extra-cellular circulating progastrin) PhD in Oncology since 2005 (Paris XI University) Master - Innovation, Valorization, Partnerships (Montpellier University) in 2013 Professional strength 12 years of fundamental research as a researcher in cancer research institutes in Europe. 8 years of R&D in biotechnology companies as Chief Scientific Officer (diagnostic and therapy). ​ Results ​ Listed as inventor for 8 patent applications, including 7 on interaction between hPG80 and cancer. Author of 10+ publications in peer-reviewed journals in the field of cancer. Co-editor at Frontiers in Oncology on the Research Topic “Therapeutic Targeting of Cancer Stem Cells- The Current State of the Art “ in 2019. ​ François Fabre Chief Financial and Operational Officer Skills Administrator of the group entities Fundraising lead Specialist in business management Master's degree in international business ​ Professional strength 8 years as managing director or general manager of companies. 5 years in cash and investment management. ​ Results Fundraising actions up to 26 M €. Drastic cost management to ensure the sustainability of this company. Monica Cappellini Development and production manager Skills 7 years of experience in R&D and production specific to hPG80 PhD in Neuroscience (University of Montpellier) ​ Professional strength 19 years of experience in start-up companies as in vivo and/or laboratory manager. Strong team management and project management. Implementation and maintenance of quality system according to ISO 13485. ​ Results Co-author in several articles related to hPG80. Successful launch of the DxPG80.Lab kit. ​ Our History Our History The dream of a scientist, the fight of a woman Dominique Joubert Senior Scientist Consultant Dominique Joubert is a scientist with a PhD in biology and over 40 years of experience in academic and fundamental research. Between 1991 and 2011, she served as Director of Research at Inserm (France) and Director of the Oncology Department at the IGF, a Joint Research Unit of CNRS, INSERM, and the University of Montpellier. Throughout her career, Dominique Joubert has challenged the prevailing scientific dogma by maintaining her belief that cancer follows the "laws of the living" and is therefore reversible. This conviction led her to search for a "key" to this reversion. In 2003, a groundbreaking observation was made in her lab on a protein that needed to exit the tumor cell and re-interact with it to exert its effect on the tumor. Dominique Joubert hypothesized that this protein, linked to disruptions in the Wnt signaling pathway (a major contributor to tumorigenesis), could be the key to reversing the tumor process. Her bold approach was met with skepticism. She proposed that neutralizing this protein could regulate the very pathway that produced it—an idea her team found far-fetched. Despite the doubts, Dominique Joubert proceeded with the experiment. To the surprise of many, the results were conclusive, providing the first demonstration that a tumor mechanism could be reversed in solid tumors. The protein in question is progastrin, the precursor of gastrin, which is found in the G cells of the stomach in healthy individuals and is absent from the bloodstream. However, in cancer patients, progastrin is secreted by tumor cells and is referred to as hPG80 . Her research has shown that hPG80 is present in the blood of 83% of cancer patients, and that 100% of tumors produce this protein. Dominique Joubert believes that this discovery will revolutionize cancer treatment. However, she recognizes the challenges ahead: the need to mobilize the necessary resources, expertise, and energy to ensure that this breakthrough in basic research translates into practical solutions for physicians and ultimately benefits patients.

DxPG80.Lab is a blood-based assay designed for the quantitative measurement of hPG 80 (circulating progastrin), a biomarker associated with cancer. Commercialized with CE marking​ Easy Rapid execution (<3 hours) Reliability Affordable CE-marked What is DxPG80.Lab test? A simple blood-based test for quantitative measurement of hPG 80 . ​ Easy, accurate, fast and non-invasive, results can be obtained within 3 hours, allowing for timely clinical decision-making. ​ Registered as CE-IVD. ​ How does DxPG80.Lab test work? The DxPG80.Lab test accurately measures hPG 80 (circulating progastrin), which is differentially expressed in blood samples from patients with various types of cancer compared to healthy individuals. Our test is based on the principle of a sandwich ELISA to measure the concentration of hPG 80 in plasma samples collected in EDTA tubes. The ELISA-based method ensures that the test provides accurate and reproducible results, which are critical for effective patient management. ​ Additional information regarding the analytical performance characteristics of the DxPG80.Lab test can be accessed here: View Manuscript Eligible population DxPG80.Lab test is indicated for adults aged 18 years or older.​ It is not intended for pregnant women. DxPG80.Lab Workflow DxPG80.Lab request The physician prescribes the DxPG80.Lab assay Blood sample DxPG80.Lab analysis DxPG80.Lab report A blood sample is taken by the diagnostic laboratory The sample is analyzed in an analytical laboratory The results are reported to the physician who informs the patient Services facility The test is intended for professional laboratory use only. ​ DxPG80.Lab test is currently performed in a state-of-the-art analysis laboratory, ensuring consistent and reliable results. Ask for our Instruction for Use View Munuscript

Publications Publications Progastrin: An Overview of Its Crucial Role in the Tumorigenesis of Gastrointestinal Cancers April 2024 Plasma hPG80 (circulating progastrin) as a novel biomarker for detecting gastric cancer: a Japanese multicenter study ​ March 2024 Association between post-operative hPG80 (circulating progastrin) detectable level and worse prognosis in glioblastoma ​ October 2023 Plasma hPG80 (Circulating Progastrin) as a Novel Prognostic Biomarker for early-stage breast cancer in a breast cancer cohort. ​ April 2023 hPG80 (circulating progastrin) as a blood biomarker for high-grade glial tumors: A pilot study January 2023 hPG80 and cancer: A new blood biomarker in development for patient monitoring June 2022 hPG80 (Circulating Progastrin), a Novel Blood-Based Biomarker for Detection of Poorly Differentiated Neuroendocrine Carcinoma and Well Differentiated Neuroendocrine Tumors February 2022 Plasma hPG80 (Circulating Progastrin) as a Novel Prognostic Biomarker for Hepatocellular Carcinoma January 2022 ​A novel method to detect hPG80 (human circulating progastrin) in the blood September 2021 Prognostic Value of Plasma hPG80 (Circulating Progastrin) in Metastatic Renal Cell Carcinoma January 2021 The oncogenic and druggable hPG80 (Progastrin) is overexpressed in multiple cancers and detected in the blood of patients December 2019 Targeting the Wnt Pathway and Cancer Stem Cells with Anti-progastrin Humanized Antibodies as a Potential Treatment for K-RAS-Mutated Colorectal Cancer September 2017