Vivoryon Therapeutics N.V. Reports Q1 2024 Financial Results and New Data
Reinforcing Strategic Focus in Kidney Disease
* Additional kidney function analyses strongly support Vivoryon's shift in
strategic focus to inflammatory and fibrotic diseases, and are a further
step towards securing Company's future
* Varoglutamstat`s beneficial effect of improving kidney function, as
demonstrated by an increase of estimated glomerular filtration rate (eGFR),
confirmed by various sensitivity and subgroup analyses
* A significant and dose dependent reduction of the pyroglutamated version of
CCL2 (pE-CCL2) in serum demonstrates effectiveness of varoglutamstat in
inhibiting systemic intracellular QPCT/L and strongly supports an anti-
inflammatory effect
* Alzheimer's disease: No consistent effect on cognition could be shown in a
subgroup of VIVIAD participants with higher drug exposure; VIVA-MIND topline
results available end 2024 to inform next steps in AD
Halle (Saale) / Munich, Germany, May 23, 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
financial results for the first quarter of 2024, ending March 31, 2024, and
provides a corporate update.
"Vivoryon has now achieved proof of concept for varoglutamstat and validated the
mechanism of action of QPCT/L inhibition. While the results in early AD were not
what we had hoped for, we are excited about the promising effect of
varoglutamstat on the pre-specified endpoint of kidney function given the
established role of pro-inflammatory cytokines and peptides in driving the
progression of kidney disease. In the past weeks, our team, which remains highly
dedicated to driving our strategic shift and transformation, has continued to
delve into the data on kidney function and we are pleased to see consistent
results. We have observed robust and meaningful improvements in eGFR in patients
treated with varoglutamstat compared to placebo across a range of different
methods assessing eGFR. Effect sizes in favor of varoglutamstat were confirmed
in patients with risk factors for CKD including diabetes and hypertension and
were observed consistently across the range of eGFR baseline impairment levels
in the study. We are now working on crystallizing our strategy and positioning
in the kidney disease market and establishing potential clinical development
plans for varoglutamstat in both large indications, such as CKD, and in certain
rare diseases that impact kidney function," said Frank Weber, MD, CEO of
Vivoryon.
Q1 2024 and Post-Period Updates
Strategic shift towards a focus on inflammatory and fibrotic diseases:
* 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. Key priorities now
include: exploring varoglutamstat's potential in inflammatory and fibrotic
disorders, including of the kidney; concluding VIVIAD Phase 2b clinical
study program and in-depth analysis; discontinuing VIVA-MIND clinical Phase
2 study with varoglutamstat in the U.S. in early AD in the second half of
2024; leveraging the data from VIVA-MIND to inform next steps in AD; and
continuing to actively pursue potential business development and financing
opportunities.
Varoglutamstat - kidney disease:
* QPCT/L inhibition has shown robust evidence of benefits in animal models of
inflammatory and fibrotic disorders such as glomerulonephritis and non-
alcoholic steatohepatitis (NASH). The VIVIAD protocol prospectively
specified measurement of kidney function by estimated glomerular filtration
rate (eGFR), a primary endpoint in many development programs of kidney
disorders, and additional biomarkers, in order to further investigate this
potential activity.
* Varoglutamstat 600mg BID increased eGFR over the treatment period up to 96
weeks in patients with early AD, indicating a potential benefit of
varoglutamstat on kidney function.
* Further sensitivity and subgroup analysis has shown this effect is observed
across the range of eGFR levels at baseline in the study, and when assessed
using a set of diverse and validated methods for calculating kidney
function.
* Additionally, the Company has explored the effect of varoglutamstat on
levels of pyroglu-CCL2 (pE-CCL2), a pro-inflammatory cytokine. Persistent,
low grade inflammation is considered a hallmark feature of chronic kidney
disease (CKD). Results showed a significant and dose-dependent reduction in
pE-CCL2 in the serum of VIVIAD patients following treatment with
varoglutamstat. This demonstrates the effectiveness of varoglutamstat in
inhibiting systemic intracellular QPCT/L and strongly supports an anti-
inflammatory effect.
* Vivoryon is evaluating a clinical development path, as well as business
development and financing opportunities, to further explore the potential of
varoglutamstat and QPCT/L inhibitors in kidney disease in both large
indications, such as CKD, and in certain rare diseases that impact kidney
function, such as Alport Syndrome.
Primary analysis of change of estimated glomerular filtration rate (eGFR, slope
analysis including all measurement timepoints during treatment):
+--------------------+-------------------+--------+-------------------+--------+
| |Annualized change |P-Value |Annualized Change |P-Value |
| |of eGFR* | |of eGFR* | |
+--------------------+-------------------+--------+-------------------+--------+
|Formula (creatinine)|MDRD |CKD-EPI 2021 |
+--------------------+-------------------+--------+-------------------+--------+
|Placebo |-1.51 | |-0.75 | |
+--------------------+-------------------+--------+-------------------+--------+
|Varoglutamstat |+1.92 | |+1.44 | |
+--------------------+-------------------+--------+-------------------+--------+
|Treatment Effect (?)|3.43 |p=0.0002|2.19 |p=0.0015|
+--------------------+-------------------+--------+-------------------+--------+
* mL/min/1.73m(2)/year
Sensitivity analysis of estimated glomerular filtration (eGFR) rate using
Cystatin C and Creatinine (remeasured on Atellica(®) platform) CKD-EPI 2021
formula at baseline, week 24 and week 48:
+---------------------+---------------+-----------------------+---------------+
| |Cystatin C |Cystatin C and |Creatinine |
| | |Creatinine | |
+---------------------+-------+-------+-------+---------------+-------+-------+
| |Week 24|Week 48|Week 24|Week 48 |Week 24|Week 48|
+---------------------+-------+-------+-------+---------------+-------+-------+
|Placebo |73.88 |71.39 |84.15 |82.07 |89.74 |88.74 |
|(eGFR mL/min) | | | | | | |
+---------------------+-------+-------+-------+---------------+-------+-------+
|Varoglutamstat |78.15 |80.88 |88.91 |91.21 |93.33 |93.98 |
|(eGFR mL/min) | | | | | | |
+---------------------+-------+-------+-------+---------------+-------+-------+
|Treatment Effect* (?)|4.27 |9.49 |4.76 |9.14 |3.59 |5.24 |
+---------------------+-------+-------+-------+---------------+-------+-------+
|P-Value |0.0186 |Â