QPCT

A meta-analysis of VIVIAD and VIVA-MIND1 data confirmed that treatment with varoglutamstat at 600mg twice daily significantly improved eGFR2 kidney function in the overall study population The meta-analysis also confirmed a substantially larger effect size in study participants with diabetes3 compared to those without diabetes Vivoryon further strengthened its patent portfolio for varoglutamstat in kidney disease, including patent filings on medical use, dosing and a new composition of matter patent on the active polymorph A novel, next-generation QPCT/L inhibitor candidate with compelling pharmacological activity was nominated for development in inflammatory and fibrotic diseases, including potentially in DKD/CKD and orphan diseases January 14, 2025 - Vivoryon Therapeutics N.V. (Euronext Amsterdam: VVY; NL00150002Q7) (Vivoryon), a clinical stage company focused on the discovery and development of small molecule medicines to modulate the activity and stability of pathologically altered proteins, today provided an update on the Company’s progress of varoglutamstat development in kidney disease and efforts to solidify its QPCT/L inhibitor pipeline in inflammatory and fibrotic diseases. “Vivoryon has thoroughly analyzed kidney function data of the two independent Phase 2 studies VIVIAD and VIVA-MIND. The results were highly consistent between the two studies which were carried out in different regions (EU vs U.S.) and with different CROs and laboratories. In both studies, a significant improvement in kidney function measured by eGFR was demonstrated in the overall population and, also in both studies, patients with diabetes displayed a substantially larger effect size than patients without diabetes. These findings were confirmed by a recently completed meta-analysis,” said Frank Weber, MD, CEO of Vivoryon. “We also enhanced the value of our development pipeline by adding three new patent filings to our patent portfolio, including a composition of matter patent of the active polymorph for varoglutamstat, as well as by identifying and nominating a novel and potent QPCT/L inhibitor for development in inflammatory and fibrotic diseases. Vivoryon is developing a highly innovative, focused portfolio of QPTC/L inhibitors grounded in the proof that QPCT/L inhibition leads to reduction in the activity of potent pro-inflammatory and fibrotic peptides.” A total of 286 patients were randomized into the 600mg twice daily (BID) varoglutamstat and placebo groups in VIVIAD and VIVA-MIND studies, with 112 allocated to 600mg BID varoglutamstat and 174 to placebo. Meta-analysis of VIVIAD and VIVA-MIND data confirmed that treatment with varoglutamstat at 600mg BID significantly improved kidney function as measured by eGFR (estimated glomerular filtration rate) in the overall population. The difference of change from baseline in eGFR between varoglutamstat and placebo became significant starting after 24 weeks of treatment and the treatment effect was maintained throughout the study duration up to 2 years (96 weeks). See Figure 1 A total of 39 patients with diabetes were randomized into the 600mg BID varoglutamstat (n=19) and placebo (n=20) groups in total (VIVIAD n=23, VIVA-MIND n=16). The corresponding numbers for study participants without diabetes were 93 patients randomized to varoglutamstat 600mg BID and 154 patients randomized to placebo (total n=247). The effect size is substantially larger in patients with diabetes compared to patients without diabetes, starting 24 weeks after initiation of treatment and sustained until the end of treatment. The results were consistent between VIVIAD and VIVA-MIND. A positive and statistically significant treatment effect was also observed in patients without diabetes. See Figure 2 Vivoryon’s key strategic priority for 2025 is to advance varoglutamstat in kidney disease and confirm the previously reported compelling data from two independent Phase 2 studies, VIVIAD and VIVA-MIND, by conducting a Phase 2b clinical study in patients with advanced diabetic kidney disease (DKD). The proposed study is expected to include up to 120 subjects with stage 3b/4 DKD, randomized 1:1 to varoglutamstat 600mg orally twice daily or placebo, on top of standard of care medications. Intended endpoints include eGFR slope analysis, measures of albuminuria (UA(p)CR), inflammation and fibrosis-related biomarkers, as well as safety. Exploring the potential of varoglutamstat in rare kidney diseases, depending on additional non-clinical data, the Company intends to initiate a small proof of concept study of varoglutamstat in orphan kidney disorders. Initiation of all future studies is subject to additional funding and/or partnership, which Vivoryon will continue to actively explore. Vivoryon has a strong patent portfolio for QPTC/L inhibition. As of December 31, 2024, Vivoryon’s patent portfolio consisted of 20 owned patent families, which comprise approximately 402 national patent applications and issued patents. In 2024, the Company further strengthened the patent portfolio with regard to its frontrunner molecule varoglutamstat (PQ912) and applications in kidney diseases. These activities included patent filings on (1) medical use in kidney diseases, (2) dosing and (3) a new composition of matter patent on the active polymorph form for PQ912, which, if granted, would extend the natural patent runtime for PQ912 to 2044. This patent was filed in mid-2023 and prioritized examination for this composition of matter patent has been initiated. The examination process and potential granting should be expected within 12 months. The Company has enlarged its portfolio by nominating a novel, next generation QPCT/L inhibitor showing compelling pharmacological activity. This candidate, VY2149, is a potential fast follower in DKD or could also be explored for other inflammatory and fibrotic diseases including orphan diseases and chronic kidney disease (CKD). VY2149 is expected to enter formal, late-stage preclinical development within this year, subject to additional funding and/or partnership, which Vivoryon will continue to actively explore. The Company will be hosting investor meetings January 14/15, 2025 around the J. P. Morgan conference in San Francisco, at which these updates will be shared. You can find a copy of the presentation that will be used in the investor meetings, including updated data from the VIVIAD/VIVA-MIND meta-analysis in the Investor section on the Company’s website at https://www.vivoryon.com/news-and-events/presentations-webcasts/. 1 VIVIAD and VIVA-MIND Phase 2 studies in early Alzheimer's disease (AD) included prospectively defined measures of kidney function as safety and other exploratory endpoints, the primary and secondary endpoints in early AD were not met 2 eGFR: estimated glomerular filtration rate, a validated measure of kidney function 3 Defined as patients having at baseline either medical history of diabetes (type 1 or 2) and/or comedication with drugs used in diabetes and/or untreated with an HbA1c > 6.5% Varoglutamstat (PQ912) is a proprietary, potent and selective inhibitor of human glutaminyl cyclases QPCT and QPCTL with therapeutic potential in indications including inflammatory and fibrotic diseases, neurodegenerative diseases, cancer and others. Initially advanced development aiming to treat Alzheimer’s disease (AD), varoglutamstat has been investigated in a number of different clinical studies. Based on the known anti-inflammatory and anti-fibrotic activity of varoglutamstat, the protocol for the Phase 2b VIVIAD study in early AD included the investigation of kidney function (measured using eGFR) and measurement of biomarkers of kidney inflammation and fibrosis to explore the role of QPCT/L inhibition on kidney function. eGFR was also analyzed as a prospectively defined safety parameter in the VIVA-MIND Phase 2 study in the U.S. Vivoryon is a clinical stage biotechnology company focused on developing innovative small molecule-based medicines. Driven by its passion for ground-breaking science and innovation, the Company strives to change the lives of patients in need suffering from severe diseases. The Company leverages its in-depth expertise in understanding post-translational modifications to develop medicines that modulate the activity and stability of proteins which are altered in disease settings. The Company has established a pipeline of orally available small molecule inhibitors for various indications including Alzheimer’s disease, inflammatory and fibrotic disorders, including of the kidney, and cancer. www.vivoryon.com The content above comes from the network. if any infringement, please contact us to modify.

Vivoryon Therapeutics N.V. Presents Topline Phase 2 Data fromVIVA-MIND Strongly Supporting Varoglutamstat’s Potential toImprove Kidney Function VIVA-MIND Phase 2 data confirm results of varoglutamstat’s benefit on eGFR in VIVIAD; Company now has two independent double-blind placebo-controlled Phase 2 studies demonstrating a clinically meaningful treatment effect on kidney functionTopline analysis of kidney function data in VIVA-MIND shows a statistically significant and clinically meaningful improvement of eGFR; average improvement of >4mL/min/1.73m2 with varoglutamstat versus placebo across all visits (weeks 4–72) and all patients (p<0.001) VIVA-MIND, a Phase 2 study in early Alzheimer’s disease (AD), was discontinued early and did not meet its primary and key secondary endpoints in early AD, in line with the previously reported results from VIVIAD Varoglutamstat continues to demonstrate a favorable safety and tolerability profile in VIVA-MIND with no new safety signals detected and a total of over 400 participants treated with varoglutamstat in Phase 1 and Phase 2 studies to dateFurther detail on the topline results from VIVA-MIND to be shared in the Company’s Q3 financial results webcast to be held on December 10, 2024, at 3:00 pm CET Halle (Saale) / Munich, Germany, December 9, 2024 – Vivoryon Therapeutics N.V. (Euronext Amsterdam: VVY; NL00150002Q7) (Vivoryon), a clinical stage company focused on the discovery and development of small molecule medicines to modulate the activity and stability of pathologically altered proteins, today announced positive Phase 2 topline data from its U.S. VIVA-MIND study of varoglutamstat (PQ912), an investigational oral glutaminyl cyclase (QPCT/L) inhibitor, in early AD. Analysis of kidney function data revealed a statistically significant improvement of >4mL/min/1.73m2 in the estimated glomerular filtration rate (eGFR) in patients treated with varoglutamstat 600mg BID versus placebo across all visits and all patients (weighted average weeks 4-72; p<0.001; total treated n=109; varoglutamstat n=52, placebo n=57). Analysis of eGFR was prospectively defined as a safety parameter in VIVA-MIND. These data reinforce the previously reported beneficial effect of varoglutamstat on eGFR in the completed Phase 2b VIVIAD study and support the Company’s development strategy to advance into a Phase 2 study in diabetic kidney disease (DKD)1. “In clinical development it is highly relevant to replicate results in two independent high-quality studies. The topline VIVA-MIND data showed a consistent, statistically significant and clinically meaningful improvement of kidney function, as measured by eGFR, in patients treated with varoglutamstat versus placebo and clearly corroborate previously reported results from VIVIAD,” said Frank Weber, M.D., CEO of Vivoryon. Analysis of VIVA-MIND data in AD showed no clinically meaningful and no statistically significant differences between varoglutamstat 600mg BID and placebo for the primary endpoint of CDR-SB, and key secondary endpoints including CFC2, ADAS-Cog 13, in patients treated with varoglutamstat compared to placebo, in line with the previously reported results in AD from VIVIAD. Frank Weber continued, “As for the results in AD, these confirm the data seen in VIVIAD and are therefore not unexpected. While we would have wished for a different outcome of this study, we would like to thank all patients, their families and caregivers, the Alzheimer's Disease Cooperative Study (ADCS) at the University of California San Diego School of Medicine and clinical study investigators as well as the U.S. National Institutes of Health – enabling the VIVA-MIND study through a grant – for their commitment to the study and the varoglutamstat program.” VIVA-MIND met its safety endpoints with varoglutamstat being generally well tolerated with no new safety signals observed at the 600mg BID dose. All topline VIVA-MIND results are preliminary and may be subject to change based on additional analysis and quality checks, however, the overall interpretation of the results is not expected to change significantly. The Company will provide further detail on the topline VIVA-MIND data on December 10, 2024, in its Q3 financial results webcast. Q3 Financial Results Conference Call and Webcast Vivoryon will host a conference call and webcast on December 10, 2024, at 3:00 pm CET (9:00 am ET). A Q&A session will follow the presentation of the third quarter 2024 results and operational progress updates.A live webcast and slides will be made available at: https://www.vivoryon.com/news-and-events/presentations-webcasts/ To join the conference call via phone, participants may pre-register and will receive dedicated dial-in details to easily and quickly access the call via the following website: https://register.vevent.com/register/BIf0be17873ad0409b83edd4eedbe3b7ac It is suggested participants dial into the conference call 15 minutes prior to the scheduled start time to avoid any delays in attendance. Approximately one day after the call, a slide-synchronized audio replay of the conference will be available on: https://www.vivoryon.com/news-and-events/presentations-webcasts/ Definitions and notes: 1.The timing and execution of the planned Phase 2 study is subject to additional funding / partnership. CDR-SB: Clinical Dementia Rating Sum of Boxes; CFC2: Cognitive-Functional Composite 2, ADAS-Cog-13: Alzheimer's Disease Assessment Scale cognitive subscale. ### About VIVA-MINDVIVA-MIND is a Phase 2 study that was conducted in the U.S., coordinated by the Alzheimer's Disease Cooperative Study (ADCS) at the University of California San Diego (UCSD) School of Medicine and supported by the National Institute on Aging (NIA), part of the National Institutes of Health (NIH) with a $15 million grant (NIA award number R01AG061146). The study originally sought to enroll 180 patients into the Phase 2a adaptive dose-finding portion and an additional 234 patients into the Phase 2b portion, with a total of 414 patients being treated on stable doses of varoglutamstat for 18 months. Based on the negative outcome reported from Vivoryon’s VIVIAD study, which had also investigated the dose of 600mg varoglutamstat BID in a similar patient population in early AD, VIVA-MIND was discontinued early to enable accelerated data analysis and inform the overall varoglutamstat development strategy. Due to this change, the VIVA-MIND study only recruited a smaller number of patients (112 randomized and 109 treated) into Phase 2a and did not move into Phase 2b. Varoglutamstat in Kidney DiseaseVaroglutamstat (PQ912) is a proprietary, potent and selective inhibitor of human glutaminyl cyclases QPCT and QPCTL with therapeutic potential in indications including inflammatory and fibrotic diseases, neurodegenerative diseases, cancer and others. Initially advancing development aiming to treat Alzheimer’s disease (AD), varoglutamstat has been investigated in a number of different clinical studies, all of which have consistently demonstrated a favorable safety and tolerability profile both in healthy volunteers and patients with AD. Based on the known anti-inflammatory activity of varoglutamstat, the protocol for the Phase 2 VIVIAD study in AD, which was completed in the first half of 2024, included the investigation of kidney function and measurement of biomarkers of kidney inflammation and fibrosis to explore the role of QPCT/L inhibition on kidney function. Although patients in VIVIAD were selected for their AD status and not for their kidney function level, many of them had reduced kidney function due to age and/or comorbidities. Analysis showed a statistically significant benefit of varoglutamstat on a prospectively defined key kidney function endpoint (eGFR) and a significant reduction of the pro-inflammatory cytokine pE-CCL2. A substantially higher treatment benefit of varoglutamstat on eGFR was observed in a post-hoc diabetes subgroup, triggering plans to advance varoglutamstat into Phase 2 study in DKD, which is currently in planning. About Vivoryon Therapeutics N.V.Vivoryon is a clinical stage biotechnology company focused on developing innovative small molecule-based medicines. Driven by its passion for ground-breaking science and innovation, the Company strives to change the lives of patients in need suffering from severe diseases. The Company leverages its in-depth expertise in understanding post-translational modifications to develop medicines that modulate the activity and stability of proteins which are altered in disease settings. The Company has established a pipeline of orally available small molecule inhibitors for various indications including Alzheimer’s disease, inflammatory and fibrotic disorders, including of the kidney, and cancer. www.vivoryon.com. Vivoryon Forward Looking StatementsThis press release includes forward-looking statements, including, without limitation, those regarding the business strategy, management plans and objectives for future operations of Vivoryon Therapeutics N.V. (the “Company”), estimates and projections with respect to the market for the Company’s products and forecasts and statements as to when the Company’s products may be available. Words such as “anticipate,” “believe,” “estimate,” “expect,” “forecast,” “intend,” “may,” “plan,” “project,” “predict,” “should” and “will” and similar expressions as they relate to the Company are intended to identify such forward-looking statements. These forward-looking statements are not guarantees of future performance; rather they are based on the Management’s current expectations and assumptions about future events and trends, the economy and other future conditions. The forward-looking statements involve a number of known and unknown risks and uncertainties. These risks and uncertainties and other factors could materially adversely affect the outcome and financial effects of the plans and events described herein. The Company’s results of operations, cash needs, financial condition, liquidity, prospects, future transactions, strategies or events may differ materially from those expressed or implied in such forward-looking statements and from expectations. As a result, no undue reliance should be placed on such forward-looking statements. This press release does not contain risk factors. Certain risk factors that may affect the Company’s future financial results are discussed in the published annual financial statements of the Company. This press release, including any forward-looking statements, speaks only as of the date of this press release. The Company does not assume any obligation to update any information or forward-looking statements contained herein, save for any information required to be disclosed by law. For more information, please contact: Investor ContactVivoryon Therapeutics N.V.Dr. Manuela Bader, Director IR & CommunicationEmail: IR@vivoryon.com Media ContactTrophic CommunicationsValeria Fisher or Verena SchossmannTel: +49 175 8041816 / +49 151 219 412 77Email: vivoryon@trophic.eu Attachment 2024-12-09_VVY_VIVA-MIND

Recently, Vivoryon Therapeutics presented new analysis data for varoglutamstat at the 2024 American Society of Nephrology (ASN) meeting. The data demonstrated statistically and clinically significant improvements in estimated glomerular filtration rate (eGFR) compared to placebo among those at risk of kidney disease and patients with diabetic kidney disease (DKD). The improvements exceeded baseline levels, suggesting potential recovery of kidney function. Varoglutamstat is an oral small molecule glutaminyl cyclase (QPCT) inhibitor. In June 2021, Simcere entered into a strategic regional licensing agreement with Vivoryon, obtaining rights to develop and commercialize varoglutamstat (SIM0801) and another compound in Greater China. About the latest study dataThis Phase 2b multicenter, randomized, double-blind, placebo-controlled, parallel-group dose exploration study administered varoglutamstat at doses of 300 mg or 600 mg twice daily, or placebo, for a duration of 48-96 weeks. Among elderly individuals at risk of kidney disease, the study showed that the varoglutamstat group experienced an improvement in eGFR of 3.4 mL/min/year (p<0.0001) compared to placebo, a statistically and clinically significant enhancement. In the subgroup of patients with diabetes, the improvement was approximately 8.2 mL/min/year (p=0.02). Other sensitivity analyses showed consistent results, including measurements using the CKD-EPI 2021 equation assessing both creatinine and cystatin C. In terms of safety, the varoglutamstat group exhibited good safety and tolerability, with no indications of increased proteinuria. No adverse renal impacts occurred over the two-year study period, and there were no meaningful differences in renal and metabolic adverse events in both the overall population and the diabetes subgroup. About VaroglutamstatVaroglutamstat holds potential as a treatment for inflammatory and fibrotic diseases, neurodegenerative diseases, cancer, and more. The company initially aimed to assess varoglutamstat's potential in treating Alzheimer's disease (AD), having studied it in multiple clinical trials. According to data released by the company in March 2024, the VIVIAD study did not achieve its primary endpoint nor showed significant statistical differences in changes to cognitive abilities over time. Additionally, it failed to meet key secondary endpoints measuring cognitive abilities, daily living activities questionnaire, and electroencephalogram global theta power. Although patients in the VIVIAD study were selected based on AD status rather than kidney function levels, many exhibited declining kidney function due to age and/or comorbidities. The analysis revealed that varoglutamstat’s improvements in the key kidney function endpoint (eGFR) were statistically significant. Furthermore, the company plans to conduct preclinical studies for indications related to other rare/orphan kidney diseases such as Alport syndrome and Fabry disease. About QPCT/QPCTL DrugsQPCT is known to catalyze the formation of neurotoxic N3pE amyloid proteins, which are associated with the aggregation of beta-amyloid peptides into plaques in the brains of Alzheimer's Disease (AD) patients. These proteins can also negatively impact other pathological factors of AD. Companies such as Vivoryon initially aimed to inhibit QPCT to prevent the formation of N3pE amyloid proteins, thereby potentially protecting neurons from damage.  Moreover, QPCTL is also a promising target for cancer treatment. Studies have shown that QPCT plays a role in the resistance of renal cancer to Sunitinib; downregulating QPCT can enhance the sensitivity of renal cancer cells to Sunitinib. Additionally, the methylation status of the QPCT promoter region and its expression levels could serve as biomarkers for predicting Sunitinib sensitivity in renal cancer. This makes QPCT a promising therapeutic target for reversing Sunitinib resistance in renal cancer and improving the efficacy of targeted renal cancer therapies.  ISM8207, a focal project collaboratively developed by Insilico Medicine and Fosun Pharma, has demonstrated antitumor efficacy in preclinical studies in vivo. It also exhibits favorable pharmacokinetic characteristics and safety. Furthermore, this drug possesses high tumor permeability and reduces hematological side effects, avoiding antigen sink effects. According to incomplete statistics, there are currently ten QPCT/QPCTL drugs under development. About VivoryonVivoryon is a clinical-stage biotechnology company dedicated to developing innovative small molecule drugs. Leveraging its deep expertise in post-translational modification, the company develops drugs that regulate the activity and stability of proteins altered within disease environments. Currently, Vivoryon has established a range of oral small molecule inhibitors intended for treating various conditions, including Alzheimer's Disease, inflammatory and fibrotic diseases (such as kidney disease), and cancer. About Simcere PharmaceuticalFounded in 1995, Simcere Pharmaceutical is an innovation and R&D-driven pharmaceutical company focusing on neuroscience, oncology, autoimmune, and anti-infective fields. The company promotes innovation through indigenous R&D and collaborative partnerships with multiple innovative enterprises and research institutions. According to incomplete statistics, over thirty transactions have occurred in recent years. How to obtain the latest research advancements in the field of biopharmaceuticals? 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