Vivoryon in de nierenbusines

1. DeZwarteRidder 19 juli 2024 13:17

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   • DeZwarteRidder

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   Vivoryon Therapeutics N.V. Announces New Data Showing Unique Treatment Effects of Varoglutamstat on Kidney Function in Patients with Diabetes and Outlines Proposed Clinical Development Plan in Diabetic Kidney Disease
   
   18 Jul 2024 07:00 CEST
   Issuer
   
   VIVORYON THERAPEUTICS N.V.
   
   Vivoryon Therapeutics N.V. Announces New Data Showing Unique Treatment Effects of Varoglutamstat on Kidney Function in Patients with Diabetes and Outlines Proposed Clinical Development Plan in Diabetic Kidney Disease
   
   New data confirm beneficial treatment effect of varoglutamstat on kidney function
   
   Treatment effect1 in diabetes subgroup2 of >8mL/min/1.73m2/year in estimated glomerular filtration rate (eGFR); reinforces previously reported treatment effect of 3.4mL/min/1.73m2/year (p<0.001) in the overall VIVIAD Phase 2b study population
   
   Excellent tolerability profile with no meaningful difference in adverse events between overall population and diabetes subgroup
   
   Additional health benefits including promising effects on weight loss, diastolic blood pressure and liver enzymes observed in diabetes subgroup
   
   New proposed Phase 2 clinical development plan for varoglutamstat in diabetic kidney disease announced
   
   Analyst/Investor call & webcast today, July 18, 2024, at 3:00 pm CEST / 9:00 am EDT
   
   Halle (Saale) / Munich, Germany, July 18, 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 that it will provide updates on its progress towards developing its lead asset varoglutamstat, an investigational QPCT/L inhibitor, in kidney disease during an R&D update call and webcast. The update includes new kidney function analysis in a diabetes subgroup from the VIVIAD Phase 2b study of varoglutamstat in Alzheimer’s disease, as well as the Company’s proposed development plan for varoglutamstat in its initial target indication, diabetic kidney disease (DKD).
   
   “The extremely promising data we are presenting today in a diabetes subgroup build on the strong body of evidence in the overall VIVIAD study population, where we observed a robust beneficial effect of varoglutamstat on kidney function,” said Frank Weber, MD, CEO of Vivoryon. “Specifically, new analysis reveals a significant and unique treatment effect in patients with diabetes which is coupled with additional potential health benefits on weight and blood pressure, and an excellent safety profile. Given these compelling results, we plan to advance varoglutamstat into a Phase 2 clinical study in patients with diabetic kidney disease, specifically in more advanced patients with a high risk of end stage kidney disease where there continues to be a significant unmet need for new therapies to stabilize and protect kidney function.”
   
   R&D Update: Key Highlights
   
   Significant Effect of Varoglutamstat in Diabetes Subgroup2
   
   New analysis of eGFR, a measure of kidney function, in a subgroup of patients with diabetes1 in the VIVIAD Phase 2b study reveals a substantially higher treatment effect3 of >8mL/min/1.73m2/year (p=0.02; varoglutamstat n=20 / placebo n=12) compared to the overall VIVIAD study population where the treatment effect was 3.4mL/min/1.73m2/year (p<0.001; varoglutamstat n=141 / placebo n=117).
   Promising additional effects observed in the diabetes subgroup in varoglutamstat treated patients included
   a reduction in liver transaminases (AST/ALT4 reduction of 6 units average)
   a mild weight loss (- 4kg)
   a reduction in diastolic blood pressure (- 6 mmHg)
   All results reported were observed at 48 weeks of treatment versus baseline. Similar observations were not made in the placebo group nor in the overall VIVIAD study population.
   Data revealed that the positive effect on kidney function in the diabetes subgroup appears to be independent of any change in glycemic control (HbA1C remained steady over the period for the varoglutamstat group).
   A reduction of the plasma concentration of the inflammatory and fibrosis inducing pE-CCL2 (p=0.004) was observed in the varoglutamstat arm, indicating a strong anti-inflammatory effect.
   Varoglutamstat was well-tolerated at the dose tested (up to 600mg twice daily) and there were no meaningful differences in adverse events observed in renal and metabolic system organ classes versus placebo or the total population.
   
   Proposed Clinical Development Plan in Diabetic Kidney Disease5
   
   Despite advances in the standard of care for DKD, there remains a significant unmet need for new therapies to stabilize kidney function and prevent disease progression.
   Vivoryon plans to start a Phase 2 study in DKD that is intended to include patients with disease stages more advanced than those observed in the VIVIAD Phase 2 study, enabling an expansion of the overall target patient population. The Company envisages a placebo-controlled study of up to approximately 120 subjects with stage 3b/4 DKD and >100mg/g albuminuria/proteinuria. These subjects would be randomized 1:1 to varoglutamstat 600mg twice daily or placebo, on top of standard of care medications. Key endpoints are planned to include eGFR slope analysis, measures of albuminuria (UA(p)CR), inflammation and fibrosis-related biomarkers, as well as safety.
   
   Collaborating with Key Experts to Advance Development Strategy
   
   The Company is collaborating with medical advisors and industry leaders to further shape its shift towards inflammatory/fibrotic disease, including:
   
   Tobias B. Huber, MD - Chair of the Center of Internal Medicine and Director of the III. Department of Medicine - University Medical Center Hamburg-Eppendorf (UKE), Germany. Acting as Medical Advisor for clinical study design. Research collaboration with Vivoryon focusing on pre-clinical and mechanistic activities relating to varoglutamstat and the role of QPCT/L on kidney function.
   Florian Jehle - CEO of Vifor-FMC Renal Pharma. Acting as Industry Expert Advisor to Vivoryon in the kidney field including strategic business and commercial advice.
   Kevin Carroll, PhD - CEO, KJC Statistics. Acting as statistical analysis expert, providing and calculating statistical read-outs and advising on clinical study statistical aspects.
   
   Detailed data and the Company's plans will be presented during the R&D update call, with the presentation available on the Vivoryon website during and after the event.
   
   Definitions and notes: 1. Treatment effect – the between-group difference in eGFR slope between varoglutamstat and placebo. 2. Estimated glomerular filtration rate (eGFR), a validated measure of kidney function, was calculated as a slope analysis across two years taking all available data into account. 3. Diabetes subgroup 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%. 4. AST: Aspartate Aminotransferase; ALT: Alanine Aminotransferase. 5. The timing and execution of the planned Phase 2 study is subject to additional funding / partnership.
2. DeZwarteRidder 29 oktober 2024 08:59

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   • DeZwarteRidder

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   Vivoryon Therapeutics N.V. Presents Outstanding Phase 2b Results of Varoglutamstat on Kidney Function at ASN Kidney Week 2024
   
   Selected for late-breaking oral presentation at ASN kidney week, the world’s premier nephrology meeting
   Results presented show a statistically significant and clinically meaningful improvement of the prospectively defined kidney function parameter eGFR1 by 3.4mL/min/year (p<0.0001) in the varoglutamstat arm compared to placebo
   Results in the subgroup of patients with diabetes2 showed an 8.2mL/min/year difference in favor of varoglutamstat (p=0.02)
   The results were consistent in several sensitivity analyses including using the CKD-EPI 2021 formula for both creatinine and cystatin-C
   Varoglutamstat demonstrated an excellent safety and tolerability profile and there were no signs of increased proteinuria
   A new Phase 2 study is in planning to confirm the effect in patients with DKD3 stage 3b and 4
   
   Halle (Saale) / Munich, Germany, October 26, 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 highlights from a late-breaking oral presentation held yesterday, October 25, 2024, at the American Society of Nephrology (ASN) Kidney Week 2024 in San Diego, California.
   
   The presentation by the Company’s CEO, Frank Weber, M.D. titled “Varoglutamstat Increases Glomerular Filtration in Elderly Patients without Signs of Proteinuria and Potentially Offers a New Approach to Treat Diabetic Kidney Disease (DKD)” featured Phase 2 clinical study data substantiating the opportunity to further develop varoglutamstat, Vivoryon’s Phase 2 investigational medicine with the potential to improve kidney function, in people with kidney disease.
   
   “We’re privileged to have been accepted to share the exciting results of varoglutamstat on kidney function with so many scientific and medical experts in the kidney field. Varoglutamstat showed statistically significant and clinically meaningful improvements of eGFR versus placebo and a sustained improvement of eGFR above baseline, potentially indicating partial recovery of the kidney. We are grateful for many fruitful discussions and extremely encouraged by the positive reactions we received from the community,” said Frank Weber, M.D., CEO of Vivoryon. “The efficacy and safety data presented at ASN represent a unique profile for an oral product for treating kidney disorders and guide the future development of varoglutamstat. Our primary focus is delivering a much-needed novel treatment option for patients suffering from DKD. Beyond this, we see potential for varoglutamstat across a broad range of kidney diseases including rare diseases affecting kidney function, such as Fabry disease and Alport syndrome.”
3. DeZwarteRidder 29 april 2025 09:04

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   • DeZwarteRidder

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   Geen omzet voor biotechbedrijf in 2024.
   
   (ABM FN-Dow Jones) Vivoryon heeft in 2024 een kleiner verlies geboekt, terwijl er geen omzet in de boeken kwam. Dit bleek dinsdagochtend uit de cijfers van het Duitse biotechbedrijf met een notering aan Euronext Amsterdam.
   
   "2024 is een transformatiejaar voor Vivoryon, omdat we met succes de strategische verschuiving naar nierziekten hebben gemaakt", zei CEO Frank Weber in een toelichting.
   
   Het nettoverlies kwam vorig jaar uit op 20,6 miljoen euro, waar dat een jaar eerder nog 28,3 miljoen euro was.
   
   De kosten voor onderzoek en ontwikkeling daalden in 2024 met 3,6 miljoen tot 14,1 miljoen euro, aldus Vivoryon.
   
   Eind 2024 had het bedrijf 9,4 miljoen euro in kas, terwijl de operationele kasstroom uitkwam op ruim 19 miljoen euro.
   
   Volgens Vivoryon zullen de bestaande geldmiddelen en kasequivalenten voldoende zijn om haar operationele plannen tot januari 2026 te financieren, "onder voorbehoud van onvoorziene omstandigheden."
   
   Verder wordt "voorzichtig" geïnvesteerd in de voorbereiding van de uitvoering van de nieraandoeningenstrategie van het bedrijf.
4. DeZwarteRidder 29 april 2025 10:26

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   • DeZwarteRidder

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   Vivoryon Therapeutics N.V. Reports Full Year 2024 Financial Results and Provides Business Update
   
   Successful strategic shift towards a focus on inflammatory and fibrotic diseases, in particular on kidney disease
   Varoglutamstat Phase 2 program shows highly consistent, statistically significant and clinically meaningful improvement of kidney function (eGFR) versus placebo in two independent randomized double-blind placebo-controlled studies
   Statistical evidence from meta-analysis of VIVIAD and VIVA-MIND enables efficient design of Phase 2b study in diabetic kidney disease (DKD), ideally suited to evaluate varoglutamstat in the intended target population of stage 3b and worse, and to maximize probability of success in kidney disease
   VIVIAD Phase 2b results of varoglutamstat on kidney function highlighted as late-breaking oral presentation at ASN Kidney Week in October 2024; varoglutamstat meta-analysis data accepted for oral presentation at ERA 2025 in June
   Pre-clinical data revealed synergistic effect of combination treatment with varoglutamstat and an SGLT2 inhibitor with both once and twice daily treatment
   Pursued stringent strategy for continued strengthening of IP around key assets; received notice of allowance for new varoglutamstat composition of matter patent in the U.S.
   Entered into Standby Equity Purchase Agreement (SEPA) of up to EUR 15 million with Yorkville Advisors Global, LP, a discretionary facility providing Company with financial flexibility towards advancing kidney disease strategy
   Management team strengthened with addition of Julia Neugebauer, PhD, taking on new role of Chief Operating Officer, heading IR as of May 1, 2025
   Updating financial guidance: Vivoryon now expects cash and cash equivalents to be sufficient for funding operations into January 2026, which does not include any funds raised through the SEPA with Yorkville
   Management to host a conference call today at 3:00 pm CEST (9:00 am EDT)
   
   Halle (Saale) / Munich, Germany, April 29, 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 announced financial results for the twelve-month period ended December 31, 2024, and provided an update on its corporate progress. The report is available on the Company’s website www.vivoryon.com/investors-news/finan...
   
   “2024 has been a transformative year for Vivoryon, as we have successfully navigated the strategic shift into kidney disease, with a viable commercial strategy and solid IP in place, including the recent notice of allowance for a new varoglutamstat composition of matter patent in the U.S.,” said Frank Weber, MD, CEO of Vivoryon. “Backed by the robust body of clinical evidence we have built to date, we have designed an efficient, lean and focused Phase 2b study in DKD that is ideally suited to evaluate varoglutamstat in the intended target population of stage 3b and worse, and to maximize probability of success in kidney disease. We are confident that the expansion of our management team as well as our recently announced SEPA agreement offering additional financial flexibility are important steps in securing the future of the Company as we strive to fully realize the potential of our pre-clinical and clinical pipeline.”
   
   Financial Year 2024 and Post-Period Pipeline Updates
   
   Strategic shift towards a focus on inflammatory and fibrotic diseases, in particular on kidney disease
   
   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. Following the announcement on March 4, 2024, that the VIVIAD Phase 2b study did not achieve its primary and key secondary endpoints in early AD and the subsequent results showing a significant positive effect of varoglutamstat on kidney function, Vivoryon announced on April 24, 2024, a strategic shift towards a focus on inflammatory and fibrotic diseases.
   
   Initially advancing 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 VIVIAD study included the investigation of kidney function (measured using estimated glomerular filtration rate, 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.
   
   Varoglutamstat clinical program
5. DeZwarteRidder 29 april 2025 10:27

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   • DeZwarteRidder

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   2)
   
   Mechanism of action:
   
   Post-translational modification occurs both physiologically and in disease settings and it is a crucial process to functionalize proteins. Many different post-translational modifications are catalyzed by enzymes that have become known drug targets, e.g. kinases, proteases, or methylases.
   Pyroglutamate (pE) formation, a specific post-translational modification catalyzed by the glutaminyl cyclase enzymes QPCT and QPCTL, has emerged as a central element in different diseases including neurodegenerative, inflammatory and fibrotic diseases as well as cancer.
   Varoglutamstat is a potent, highly selective oral small molecule inhibitor of human QPCT and QPCTL, designed to prevent inflammatory and fibrotic processes by blocking pyroglutamate formation on key disease drivers.
   QPCTL inhibition has demonstrated robust evidence of efficacy in animal models of inflammatory and fibrotic disorders such as glomerulonephritis and non-alcoholic steatohepatitis (NASH).
   
   VIVIAD Phase 2b results of varoglutamstat on kidney function:
   
   Results of VIVIAD Phase 2b showed a statistically significant and clinically meaningful improvement of the prospectively defined kidney function parameter eGFR by 3.4mL/min/1.73m2/year (p<0.001; slope analysis) in the varoglutamstat arm compared to placebo. Results in the subgroup of patients with diabetes showed an 8.2mL/min/1.73m2/year difference in favor of varoglutamstat (p=0.02; slope analysis).
   The results were consistent in several sensitivity analyses including using the CKD-EPI 2021 formula for both creatinine and cystatin-C.
   Varoglutamstat demonstrated an excellent safety and tolerability profile and there were no signs of increased proteinuria.
   On October 25, 2024, Vivoryon presented these results in a late-breaking oral presentation at the American Society of Nephrology (ASN) Kidney Week 2024 in San Diego, California. The presentation by the Company’s CEO, Frank Weber, MD titled “Varoglutamstat Increases Glomerular Filtration in Elderly Patients without Signs of Proteinuria and Potentially Offers a New Approach to Treat Diabetic Kidney Disease (DKD)” featured Phase 2b clinical study data from VIVIAD substantiating the opportunity to further develop varoglutamstat in people with kidney disease.
   
   VIVA-MIND Phase 2 data confirm results of varoglutamstat’s benefit on eGFR in VIVIAD:
   
   On December 9, 2024, the Company reported topline results from the VIVA-MIND Phase 2 study of varoglutamstat in early AD, corroborating earlier reports of varoglutamstat’s beneficial effect on kidney function as measured by eGFR. VIVA-MIND 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.
   Topline analysis of kidney function data showed 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=0.004; mean weighted average).
   Varoglutamstat continued to demonstrate a favorable safety and tolerability profile in VIVA-MIND with no new safety signals detected with a total of over 400 participants treated with varoglutamstat in Phase 1 and Phase 2 studies to date.
   
   Meta-analysis of VIVIAD and VIVA-MIND study data:
   
   On January 14, 2025, the Company disclosed a meta-analysis of VIVIAD and VIVA-MIND data which confirmed that treatment with varoglutamstat at 600mg twice daily significantly improved eGFR kidney function in the overall study population. The meta-analysis also confirmed a substantially larger effect size in study participants with diabetes compared to those without diabetes.
   
   All Patients:
   
   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 in the overall population.
   The difference in 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).
   
   Stratification in Patients with Diabetes and without Diabetes:
   
   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 was 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.
   
   Meta-analysis data from VIVIAD and VIVA-MIND was accepted for oral presentation at the 62nd European Renal Association (ERA) Congress 2025, to be held in Vienna, Austria, June 4-7, 2025.
   
   Presentation details
   
   Title: Varoglutamstat improves eGFR and offers a new approach to treat diabetic kidney disease (DKD): meta-analysis from two independent phase 2 studies.
   
   Date/Time: June 6, 2025, 8:15 CEST
   
   Presenter: Frank Weber, MD