University of Navarra

Vivet Therapeutics Presents Three Posters on Cerebrotendinous Xanthomatosis Program and Novel AAV Gene Delivery Platform at European Society of Gene and Cell Therapy Annual Congress 2024 Paris, France, October 22, 2024 – Vivet Therapeutics (“Vivet”), a clinical stage biotech company developing novel and long-lasting gene therapies for rare inherited liver metabolic disorders, today announces the presentation of three posters demonstrating key pre-clinical findings for its gene therapy program, VTX-806 for the treatment of Cerebrotendinous Xanthomatosis (CTX), a study on S/MAR-containing AAV vector integration in hereditary tyrosinemia type I (HT1) and validation of the translational value of the B6.129-Cyp27a1tmlEl t/J CTX mouse model at the European Society for Gene and Cell Therapy (ESGCT) 2024 Congress Rome, Italy from the 22-25 October. Dr Gloria Gonzalez-Aseguinolaza, Co-Founder & Chief Scientific Officer at Vivet Therapeutics, said, “Our findings highlight the potential of our diversified gene therapy pipeline, using our precise, highly engineered, next-generation viral vectors and gene constructs. We are committed to developing long-lasting AAV-based gene therapies for CTX and other rare inherited liver metabolic disorders to ultimately provide more effective treatment options for patients. Dr Jean-Philippe Combal, Co-Founder & Chief Executive Officer at Vivet Therapeutics added, “The existing standard of care (SOC) for CTX is a lifelong treatment using chenodeoxycholic acid which reduces the levels of toxic metabolites but does not 100% prevent neurodegeneration, leaving an unmet medical need. Our preclinical findings for VTX-806 provide further evidence that VTX-806 holds promise for curative treatment for CTX as underlined by our data and the European Orphan Drug Designation received in September of this year. We look forward to presenting further groundbreaking data at upcoming scientific conferences as we drive the program forward.” Poster one entitled “Long-term metabolic, phenotypic, and neuropathological characterization of the Cyp27a1-/- mouse model of cerebrotendinous xanthomatosis,” details the long-term evaluation of B6.129-Cyp27a1tmlEl t/J, a CTX mouse model with full metabolic, phenotypic, histological and neuropathological characterization up to 18 months of age. The study confirmed prior literature in that Cyp27a1-/- mice when compared to their wild-type (WT) littermates, had hepatomegaly, increased levels of plasma ALT, and increased expression of Cyp7a1 and Cyp3a11. Cyp3a11 is a homolog to human CYP3A4, an enzyme that metabolizes large portions of drugs and other foreign objects in the body. At six months of age, Cyp27a1-/- mice presented lower body weight gain and steatosis, alongside elevated toxic bile acid precursors in circulation and in the brain. In addition, Cyp27a1-/- mice presented signs of ataxia, particularly in females, making this study the first to show measurable motor alterations in a mouse model with CTX, like those described in CTX patients, making this a valuable model for translational CTX research. Poster two entitled “S/MAR-Containing AAV Vectors Result in an Increase in AAV Episomes and a Reduction in AAV Integration Sites in a Mouse Model With a High Rate of Hepatocyte Proliferation,” details an S/MAR (scaffold/matrix attachment region) containing AAV vector integration study in an HT1 mouse model (Fah1R Tyrc/RJ). Results showed that the S/MAR-containing AAVs achieved a higher therapeutic effect than the control vector. Surviving mice showed body weight (BW) and serum biomarker (SB) normalization after approximately 50 days post-injection and the number of viral genomes and disease-associated enzyme (Hfah) expression levels were similar across experimental groups. Immunohistochemistry (IHC) also showed FAH expression in clusters of positive hepatocytes in recovered mice, suggesting potential AAV integration and clonal expansion. These results not only indicate the presence of the S/MAR sequence but also suggest the location of the S/MAR sequence within the therapeutic vector, influences the fate of the viral genome in the transduced cell. Poster three entitled “Liver-directed gene therapy normalizes toxic bile acid metabolite levels in the blood and brain of mice with cerebrotendinous xanthomatosis,” details the development and optimization of VTX-806, as an adeno-associated virus (AAV) vector with high potency and low immunogenicity. AAVs were optimized using Cyp27a1 expression cassettes containing a liver-specific promoter designed to prevent potential activation of an innate immune response and added regulatory elements: minute virus of mice small intron (MVM) and Woodchuck Hepatitis Virus post-transcriptional regulatory element (WPRE). Results demonstrated in vitro and in vivo higher Cyp27a1 expression with VTX-806, restoring normal levels of circulating 7αC4, expression of hepatic bile acid synthesis-related genes, and corrected hepatomegaly. Importantly, normal levels of 7αC4 were restored in the brain. These results demonstrate for the first time that liver-directed AAV gene therapy can normalize levels of toxic metabolites in the brain, offering a potentially effective and curative treatment option for CTX patients. Details of poster presentations are as follow: Poster Title: Long-term metabolic, phenotypic, and neuropathological characterization of the Cyp27a1-/- mouse model of cerebrotendinous xanthomatosis Poster Number: P0381Presenter: Laia Trigueros Motos, Research Scientist at Vivet TherapeuticsDate and Time: Tuesday 22 October at 19:30-21:00 CESTLocation: Forum Poster Title: S/MAR-Containing AAV Vectors Result in an Increase in AAV Episomes and a Reduction in AAV Integration Sites in a Mouse Model With a High Rate of Hepatocyte Proliferation Poster Number: P0138Presenter: Andrea Llanos Ardaiz, PhD Apprentice at Vivet TherapeuticsDate and Time: Wednesday 23 October at 13:30-15:00 CESTLocation: Concourse Level – 1 and Mezzanine Concourse Poster Title: Liver-directed gene therapy normalizes toxic bile acid metabolite levels in the blood and brain of mice with cerebrotendinous xanthomatosis Poster Number: P0888Presenter: Laia Trigueros Motos, Research Scientist at Vivet TherapeuticsDate and Time: Thursday 24 October at 18:00-19:30 CESTLocation: Concourse Level – 1 and Mezzanine Concourse Poster 1 Authors: L Trigueros-Motos3,‡, A Molina1,2,‡, G Pérez1,2, I Marcilla1,2, M Molina1,2, L Neri3, D Moreno-Luqui1,2, A Douar4, JP Combal4, A García-Osta 1,2, M Cuadrado-Tejedor 1,2, B Tamarit4, C Bouquet4, G Despres5, P Krasniqi5, A Lamazière5, 6, R Hernandez-Alcoceba1, G González-Aseguinolaza1,2,3,* 1 Division of DNA and RNA Medicine, CIMA, University of Navarra, Pamplona, Spain 2 Institute for Sanitary Research (IdiSNA), Pamplona, Spain 3 Vivet Therapeutics S.L., Spain 4 Vivet Therapeutics S.A.S., Paris, France 5 Sorbonne Université, Saint Antoine Research Center, INSERM UMR 938, Paris, France 6 Département de Métabolomique Clinique, Hôpital Saint Antoine, AP-HP, Sorbonne Université, Paris, France ‡Equal contribution, *ggonzalez@vivet-therapeutics.com Poster 2 Authors: A Llanos-Ardaiz1, A Lantero1, M Ruiz de Galarreta1, L Neri1, I Mauleón 2, M Bilbao-Arribas 2,3, B Tamarit4, V Ferrer4, A Douar4, JP Combal4, R Aldabe2, G Gonzalez-Aseguinolaza 1,2 1 Vivet Therapeutics S.L., Pamplona, Spain. 2 DNA & RNA Medicine Division, Centre for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain. 3 IdISNA, Navarra Institute for Health Research, Pamplona, Spain. 4 Vivet Therapeutics S.A.S., Paris, France Poster 3 Authors: A Molina1,2,‡, L Trigueros-Moto 3,‡, G Pérez1,2, M Molina1,2, I Marcilla-García1,2, L Neri3, A Douar4, JP Combal4, B Tamarit4, C Bouquet 4, P Krasniqi 5, A Lamazière5, 6, R Hernandez-Alcoceba1, G González-Aseguinolaza1,2,3,* 1 Division of DNA and RNA Medicine, CIMA, University of Navarra, Pamplona, Spain 2 Institute for Sanitary Research (IdiSNA), Pamplona, Spain 3 Vivet Therapeutics S.L., Spain 4 Vivet Therapeutics S.A.S., Paris, France 5 Sorbonne Université, Saint Antoine Research Center, INSERM UMR 938, Paris, France 6 Département de Métabolomique Clinique, Hôpital Saint Antoine, AP-HP, Sorbonne Université, Paris, France ‡Equal contribution, *ggonzalez@vivet-therapeutics.com -Ends- For further information, please contact: Optimum Strategic Communications Mary Clark, Zoe Bolt, Vareen OuthonesackTel: +44 (0) 20 3882 9621Email: vivet@optimumcomms.com About Vivet Therapeutics Vivet Therapeutics is a private, clinical-stage biotech company developing novel and long-lasting gene therapies for rare inherited metabolic conditions, including Wilson’s Disease. Vivet’s gene therapy platform uses recombinant adeno-associated viruses (rAAVs) as vectors and has initiated two clinical programs and four pre-clinical assets to date. Its most advanced program VTX-PID, is aimed at depleting Neutralizing Antibodies (NAbs) levels for a given AAV serotype and is advancing in a Phase 1 dose escalating study in Nabs+ subjects. Its Leading pre-clinical program VTX-806, for the treatment of Cerebrotendinous Xanthomatosis (CTX), received ODD by the EC in September 2024 and is demonstrating its potential as an alternative treatment option for patients affected by the burden of CTX. Vivet Therapeutics was founded in 2016 by CEO Dr Jean-Philippe Combal and CSO Dr Gloria Gonzalez-Aseguinolaza and is led by a highly experienced management team with deep expertise developing gene therapies and orphan drugs. Vivet Therapeutics was founded in 2016 by CEO Dr Jean-Philippe Combal and CSO Dr Gloria Gonzalez-Aseguinolaza and is led by a highly experienced management team with deep expertise developing gene therapies and orphan drugs. Vivet Therapeutics is backed by international life science investors including Novartis Venture Fund, Roche Venture Fund, HealthCap, Pfizer Inc., Columbus Venture Partners, Ysios Capital, Kurma Partners and Eurazeo. In 2019, key investor Pfizer contributed a €45M investment to collaborate with Vivet in recognition of its scientific expertise and innovative technology platforms. For more information, please visit www.vivet-therapeutics.com - Follow us on LinkedIn @Vivet Therapeutics and Twitter @Vivet_tx…………………………

Assembles Global Dream Team and Establishes Scientific Advisory Board to Accelerate Myeloma ResearchSTUDIO CITY, Calif., July 03, 2024 (GLOBE NEWSWIRE) -- The International Myeloma Foundation (IMF) today announced that IMF Co-Founder Dr. Brian G.M. Durie‘s last day as IMF Chief Scientific Officer will be on July 8, 2024. Dr. Durie will continue to be a member of the IMF Board of Directors. In 1990, Dr. Durie, along with Brian Novis and Susie Novis Durie, founded the International Myeloma Foundation (IMF)—a non-profit that is dedicated to serving the global myeloma community. When the IMF was established, very little was known about multiple myeloma and the IMF founders set out to educate patients about the disease and the very limited available treatment options. As the organization grew, the four founding pillars of research, education, support, and advocacy became its foundation, for which it still stands. Due to Dr. Durie’s remarkable scientific and organizational leadership for the previous 35 years, the IMF continues to thrive, making advances in the field of myeloma, and dedicating to its mission of improving the quality of life for myeloma patients while working toward prevention and a cure. “We deeply appreciate Dr. Durie’s invaluable contributions, which have shaped the IMF and the myeloma community into what it is today,” said IMF President & CEO and 28-year myeloma patient Yelak Biru. “Dr. Durie’s reputation for innovation in the field of myeloma globally has allowed the IMF to develop in ways no one could have imagined. The IMF was the first of its kind in many arenas. That pioneering mindset contributed to groundbreaking research and the development of invaluable patient support services, offering a brighter future for those diagnosed with multiple myeloma,” continued Mr. Biru. On a personal note, Mr. Biru described how the IMF has made an impact on his life as a 28-year myeloma patient: "The IMF has empowered and continues to empower me in my 28-year myeloma journey. The IMF has been instrumental in providing information, connecting patients with a supportive community, and giving them hope for a brighter future." “I am incredibly grateful to Dr. Brian Durie for his major contributions and tireless commitment to the myeloma field and the IMF. This is a major transition point for us, and we will work hard as a team to ensure that the organization continues to grow and expand its reach in our quest to improve the lives of myeloma patients around the world through research, education, support, and advocacy. In this regard, I am glad that some of the best researchers in the myeloma field will be assisting us as members of the newly reconstituted Scientific Advisory Board,” said IMF Chairperson of the Board Dr. S. Vincent Rajkumar. Building on Dr. Durie’s more than three decades of hard work and legacy, the IMF will embark on a new scientific chapter while continuing with established IMF-funded research initiatives: the International Myeloma Working Group (IMWG); the Black Swan Research Initiative (BSRI); the iStopMM (Iceland Screens, Treats, or Prevents Multiple Myeloma) Project; the Asian Myeloma Network (AMN); the i2TEAMM’s research work on minimal residual disease (MRD); the ASCENT and CESAR Cure Trials; and the IMF Immunotherapy Registry, to name a few. The IMF will keep innovating new opportunities to amplify patient voices in research and to double down on global collaboration. The IMF continues its collaborative work with patients, renowned researchers, industry partners, and other organizations in the global fight against the second most common blood cancer in the world. To undertake this endeavor, the IMF has established a new Scientific Advisory Board. The Scientific Advisory Board includes an esteemed group of global myeloma experts (led by IMF Chairperson of the Board Dr. S. Vincent Rajkumar), who will guide and prioritize IMF research initiatives as well as identify areas for investment and expansion. Members of the newly established IMF Scientific Advisory Board include IMF Chairperson Dr. Rajkumar (Mayo Clinic—Rochester, MN), and IMF President & CEO and 28-year myeloma patient Yelak Biru, MSc (IMF—Los Angeles, CA), as well as the following world-renowned myeloma researchers: Wee Joo Chng, MD (National University Cancer Institute—Singapore); Professor and Director, National University Cancer Institute; Group Director of Research, National University Health SystemVania Hungria, MD, PhD (Santa Casa de São Paulo— São Paulo Brazil); Associate Professor of Hematology and Oncology, Santa Casa Medical School; Clinical Director, Clinica São GermanoSigurður Yngvi Kristinsson, MD, PhD (University of Iceland— Reykjavík, Iceland); Professor, University of Iceland; Consultant, Landspitali University Hospital Shaji Kumar, MD (Mayo Clinic—Rochester, MN, USA); Professor and Research Chair, Division of Hematology, Department of Internal Medicine, Mayo Clinic; Vice Chair, International Myeloma SocietySagar Lonial, MD, FACP (Winship Cancer Institute, Emory University—Atlanta, GA, USA); Professor and Chair, Department of Hematology and Medical Oncology, Emory University School of Medicine; Chief Medical Officer, Winship Cancer Institute, Emory UniversityThomas G. Martin, MD (University of California, San Francisco, CA — Helen Diller Family Comprehensive Cancer Center—San Francisco, CA, USA); Clinical Professor of Medicine, Adult Leukemia and Bone Marrow Transplantation Program, UCSF; Associate Director, Myeloma Program, UCSF; Co-Leader, Cancer immunology & Immunotherapy Program, Helen Diller Family Comprehensive Cancer CenterMaría-Victoria Mateos, MD, PhD (University of Salamanca—Salamanca, Spain); Head of Myeloma and Clinical Trials Unit, Hematology Department; Professor of Medicine, University of Salamanca; Coordinator, Spanish Myeloma Group (GEM); IMWG Smoldering MM Committee MemberJoseph Mikhael, MD (TGen, City of Hope Cancer Center—Phoenix, AZ, USA); IMF Chief Medical Officer; Professor, Applied Cancer Research and Drug Discovery Division, Translational Genomics Research Institute (TGen), City of Hope Cancer CenterPhilippe Moreau, MD (University Hospital of Nantes—Nantes, France); Head of the Hematology Department, University Hospital of Nantes; Professor, Clinical Hematology; President, International Myeloma Society; IMWG Scientific Committee Member Nikhil Munshi, MD (Dana-Farber Cancer Institute—Boston, MA, USA); Director of Basic and Correlative Science, Jerome Lipper Multiple Myeloma Center; Director, Multiple Myeloma Immune Effector Cell Therapy; Professor of Medicine, Harvard Medical School; Kraft Family Chair; IMWG Scientific Committee Member Jesús San Miguel, MD, PhD (University of Navarra—Pamplona, Spain); Professor of Medicine-Hematology and Head of Clinical and Translational Medicine, University of Navarra; Medical Director and Vice-Dean of Research, Clinica Universidad de Navarra; CIMA Scientific Director; IMWG Scientific Committee MemberSaad Z. Usmani, MD, MBA, FACP, FASCO (Memorial Sloan Kettering Cancer Center—New York, NY, USA); Myeloma Specialist and Cellular Therapist; Chief, Myeloma Service, Memorial Sloan Kettering Cancer Center “This collective leadership model will expand our reach and lean into our values of global collaboration and innovation. Engagement with a diverse group of leaders will further advance our vision of enabling every myeloma patient to live life to the fullest, unburdened by disease,” said Mr. Biru. By assembling a remarkable global dream team of renowned myeloma experts in the newly established Scientific Advisory Board, the IMF can leverage the Scientific Advisory Board’s collective knowledge and experience, identify promising new areas of research, collaborate on international research initiatives, and strengthen the scientific rigor of ongoing projects. The IMF will continue to be inspired by the remarkable legacy of its founders—Dr. Brian G.M. Durie, Susie Novis Durie, and Brian D. Novis— in realizing its mission of improving the quality of life of myeloma patients while working toward prevention and a cure. ABOUT THE INTERNATIONAL MYELOMA FOUNDATION Founded in 1990, the International Myeloma Foundation (IMF) is the first and largest global foundation focusing specifically on multiple myeloma. The Foundation's reach extends to more than 525,000 members in 140 countries worldwide. The IMF is dedicated to improving the quality of life of myeloma patients while working toward prevention and a cure by focusing on four key areas: research, education, support, and advocacy. The IMF has conducted more than 250 educational seminars worldwide, maintains a world-renowned InfoLine, and in 2001, established the International Myeloma Working Group (IMWG), a collaborative research initiative focused on improving myeloma treatment options for patients. In 2012, the IMF launched the Black Swan Research Initiative®, a groundbreaking research project aimed at curing myeloma. The IMF can be reached at (800) 452-CURE (2873). The global website is www.myeloma.org. Follow the IMF on:X: @IMFmyelomaInstagram: @imfmyelomaFacebook: @myelomaLinkedIn: International Myeloma Foundation Media Contacts: Peter AntonPanton@myeloma.org Jason LondonJlondon@myeloma.org

The results include data from three main study cohorts: In the non-squamous non-small cell lung cancer (NSCLC) cohort, an Objective Response Rate (ORR) for NSCLC of 19.0% (4/21), with 2 Partial Responses (PR) and 2 Complete Responses (CR) was observed. In the UC cohort, the ORR was 19.2% (5/26), with 4 PRs and 1 CR. In HCC, data from the first 20 patients showed an ORR of 20.0% (4/20), with 3 PRs and 1 CR in the early readouts. Exceptional Duration of Response (DoR) was observed with mean and median surpassing 15 months for NSCLC and 14 months for UC cohorts at data cut-off, with 77% of all responses still ongoing. All responses are confirmed as per RECIST 1.1, with the 4 CRs all ongoing; 3 of the 4 CRs had not experienced a CR with any prior systemic treatment, including initial/prior anti-PD-(L)1 treatment. 53.3% of all responders (PR and CR) experienced a response level/depth as per RECIST 1.1 that had not been achieved on prior/initial anti-PD-(L)1 treatment, indicative of deep, lasting immune-mediated tumor control that has not been experienced with prior/initial anti-PD-(L)1 treatment. The data were presented by the International Coordinating Investigator, Ignacio Melero, MD, PhD, in an oral presentation at the ASCO Annual Meeting 2024. MUNICH--(BUSINESS WIRE)-- CatalYm today announced positive new follow-up results from its ongoing “GDFATHER” Phase 1/2a trial (GDF-15 Antibody-mediaTed Human Effector Cell Relocation Phase 1/2a) (NCT04725474) in an oral presentation at the American Society of Clinical Oncology (ASCO) Annual Meeting 2024 in Chicago. Featuring matured data from the non-small cell lung cancer (NSCLC) and urothelial cancer (UC) cohorts, as well as novel, early data for the hepatocellular carcinoma (HCC) cohort and an additional biomarker cohort, the presentation highlighted that treatment with a combination of CatalYm’s lead candidate, visugromab, combined with the anti-PD-1 antibody nivolumab achieves compelling deep and durable anti-tumoral activity in anti-PD-1/PD-L1 relapsed/refractory patients as defined by strict criteria. The combination of visugromab and nivolumab further demonstrates an excellent safety and tolerability profile. Visugromab is a monoclonal antibody designed to neutralize the tumor-produced Growth Differentiation Factor-15 (GDF-15), a central mediator of immune resistance to cancer therapies. The oral presentation by International Coordinating Investigator Prof. Ignacio Melero, MD, PhD, Co-Director of Immunology and Immunotherapy (CIMA) at the Universidad de Navarra, Pamplona/Spain, provides further evidence for the potential of visugromab to improve the clinical response depth and duration for patients with advanced, metastatic tumors. “These recent data continue to impress us with the significant ability to generate deep partial and complete responses with enormous durability in heavily pretreated patients that have failed their approved therapies including prior anti-PD-(L)1 treatment as defined by strict criteria,” said Prof. Dr. Eugen Leo, Chief Medical Officer at CatalYm. “Remarkably, more than half of all responders experienced a response level/depth as per RECIST 1.1 (up to lasting CR) that had not been achieved on their prior/initial anti-PD-(L)1 treatment. This demonstrates that GDF-15 blockade by visugromab can induce a remission depth and durability, and long-term immunologic tumor control that other cancer immunotherapies could not induce. Visugromab may have the potential to bring us a major step closer to finally providing deep long-term tumor control and potentially cure for metastatic solid tumor patients with non-squamous NSCLC, UC, and HCC.” Summary of Key Clinical Results: The matured results from the Phase 2a indication-specific cohorts for NSCLC, UC, and all HCC so far treated show the following Objective Response Rates (ORR): non-squamous NSCLC: ORR of 19.0% (4/21), with 2 partial responses (PR) and 2 complete responses (CR) UC: ORR of 19.2% (5/26), with 4 PR and 1 CR HCC: ORR of 20.0% (4/20), with 3 PR and 1 CR in the primary early readout The DoR results indicate that visugromab may have a significant impact on deepening and prolonging responses to checkpoint inhibitor (CPI) therapy: non-squamous NSCLC and UC: mean DoR surpassed 15 and 14 months, respectively, with 7/9 responses ongoing HCC: data still maturing with 12 patients ongoing on study treatment at data cut-off in the newly initiated cohort Overall, in a total of 90 patients with the above indications treated in various cohorts (including a biomarker-oriented cohort with varying tumor types), an ORR of 16.7% across all three main tumor types is currently observed, with data partly maturing further. In totality, 8/15 RECIST 1.1 responders (53.3%) experienced a response level/depth (PR, CR) that had not been achieved with their initial CPI therapy: Complete responses (CRs): Among the 4 patients who achieved CR, 3 had no prior CR on any treatment regimen, including previous CPI treatments. Partial responses (PRs): 5/11 patients who achieved PR had no RECIST 1.1 response at all on prior CPI treatments. The combination of visugromab with nivolumab showed excellent overall tolerability, with a safety pro similar to nivolumab treatment alone: most Treatment-Emergent Adverse Events (TEAEs) were mild to moderate only 8.1% of patients experienced severe TEAEs (Grade ≥ 3) Patient sample analyses strongly support the involvement of GDF-15 in the creation of an immunosuppressed tumor microenvironment and highlight the therapeutic potential of GDF-15 neutralization in these indications: Elevated serum levels of GDF-15 were shown to correlate inversely with intratumoral T cell numbers and their proliferation in samples of patients with non-squamous NSCLC, UC, and HCC. Blockade of GDF-15 by visugromab, in combination with nivolumab treatment, resulted in the rise of serum interferon-γ levels, a critical cytokine for the stimulation of an immune response, in NSCLC and UC patients. Blockade of GDF-15 by visugromab, in combination with nivolumab treatment, resulted in the rise of serum interferon-γ inducible chemokines CXCL9 and CXCL10 which remained significantly elevated over the monitoring period of six weeks. Additional preclinical studies indicated that GDF-15 was significantly elevated by standard cancer treatments, specifically e.g. platinum-based chemotherapies, checkpoint inhibitor treatment, and respective combinations. This is another layer of support for the significant role of GDF-15 in the development of immune resistance to these treatment regimens and reason to develop visugromab in the first- and second- line settings where these agents are in standard use. “We have designed a broad Phase 2b development plan to thoroughly investigate where visugromab can have its biggest impact for patients. These new results further confirm that neutralizing GDF-15 may be a critical strategy in overcoming cancer therapy resistance by breaking immunosuppressive barriers that currently limit therapeutic outcomes,” said Phil L’Huillier, Managing Director and Chief Executing Officer at CatalYm. “Validated by the strong clinical and preclinical data on visugromab’s mechanism of action and GDF-15’s relevance in therapeutic resistance to date, we will now investigate the clinical benefit of visugromab in first- and second-line treatment and there in combination with standard-of-care that has been shown to increase GDF-15 levels further on top of the tumoral production of GDF-15. It is our goal to significantly improve patient responses and establish a new benchmark in cancer care.” The Phase 2a GDFATHER-2 program was initiated in March 2022. The ongoing study consists of two segments with up to seven cohorts and is expected to enroll over 200 patients in various cohorts. An evaluation of potential response-predictive biomarker(s) is ongoing. Based on a previous positive readout presented at the ESMO IO Congress in 12/2023, CatalYm is in preparations to launch randomized, controlled studies in several major cancer indications in combination with checkpoint inhibitors and standard-of-care in first- and second-line treatment in the first half of 2025. Presentation Details Title: Effects of neutralization of tumor-derived immunosuppressant GDF-15 on anti-PD-1 activity in anti-PD-(L)1 relapsed/refractory non-squamous NSCLC, urothelial, and hepatocellular cancer Presenter: Dr. Ignacio Melero Bermejo, MD | Clinica Universidad de Navarra Abstract Number: 2513 Date and time: Sunday, June 2, 2024, from 11:30 AM – 1:00 PM CDT About the GDFATHER-2 Trials The GDFATHER-2 trial (GDF-15 Antibody-mediaTed Human Effector cell Relocation Phase 2) (NCT04725474) is the Phase 2a part of the ongoing Phase 1/2a trial with several cohorts investigating the effect of visugromab (CTL-002) in combination with a PD-1 checkpoint inhibitor in patients in various advanced-stage/last-line and by strict criteria anti-PD1/PD-L1 relapsed/refractory solid tumor types. The study can enroll up to 200 patients and has extensive biomarker-evaluations integrated to assess for potential responder patient population identification or similar. About Visugromab (CTL-002) Visugromab is a monoclonal antibody that neutralizes the tumor-derived Growth Differentiation Factor-15 (GDF-15), a locally acting immunosuppressant fostering immunotherapy resistance. Neutralizing GDF-15 with visugromab reverses key cancer resistance mechanisms to reinstate an efficient anti-tumor response by reenabling immune cell activation and tumor infiltration. Visugromab has demonstrated a good safety pro potent and durable anti-tumor efficacy in combination with anti-PD-1 treatment in advanced cancer patients The antibody is currently being investigated in ongoing Phase 2a studies in multiple solid tumor indications. About CatalYm CatalYm has identified GDF-15 as a key cancer therapy resistance mechanism and is developing it as safe and efficacious immune therapy for solid tumors. GDF-15, an immunosuppressant important for feto-maternal tolerance, is hijacked by cancer cells to evade immune system attack. Visugromab, CatalYm’s lead antibody, has demonstrated durable anti-tumor efficacy with long-lasting objective responses in relapsed and refractory metastatic solid tumor patients in combination with anti-PD-1 treatment. CatalYm is now advancing to Phase 2b studies to confirm visugromab as a new class of cancer immunotherapy in a broad range of anti-cancer regimens. View source version on businesswire.com: Contacts CatalYm GmbH Dr. Phil L’Huilier, CEO info@catalym.com Media Inquiries Trophic Communications Dr. Stephanie May or Dr. Alison Opalko Phone: +49 171 185 56 82 or +49 151 54041130 catalym@trophic.eu Source: CatalYm GmbH View this news release online at: