Mineralys Therapeutics : Corporate Overview April 2025

Published: 2025-04-01 08:21:22 ET MLYS

Targeting Aldosterone in the Treatment of Cardiorenal Diseases

April 2025

Mineralys:

Targeting Aldosterone in the Treatment of Hypertension, CKD, OSA and Beyond

Lorundrostat is a selective aldosterone synthase inhibitor (ASI) targeting aldosterone

Obesity epidemic is driving abnormally elevated aldosterone contributing to hypertension, CKD, OSA and heart failure

Launch-HTN: 19.0mmHg absolute and 11.7mmHg placebo-adjusted reduction (p<0.0001) with 50mg QD at week 12 demonstrated the meaningful clinical benefit, safety and tolerability in "real-world" setting

Advance-HTN: 15.4mmHg absolute and 7.9mmHg placebo adjusted reduction (p=0.001) with 50mg QD at 12 weeks demonstrated the meaningful clinical benefit, safety and tolerability in "specialist" setting

Proof-of-Concept CKD and hypertension trial topline data anticipated in 2Q 2025

Proof-of-Concept OSA and hypertension initiated in 1Q 2025

Lorundrostat Potential Benefit Across Spectrum of CRMS

Targeting dysregulated aldosterone in overlapping CRMS conditions with high CV risk and large unmet need

High prevalence of aldo in u/rHTN Obesity link to dysregulated aldo ~20M u/rHTN patients

Abnormally Elevated Aldosterone Impacts Multiple Biological

Pathways and Is a Key Driver in Cardiorenal Diseases

Non-Genomic Effects

(GPR30 receptor)

Drives endothelial and renal tubular oxidative stress, microvascular fibrosis, inflammation and HF

Aldosterone-driven Cardiorenal Disorders

1. Sim JJ, Bhandari SK, Shi J, et al. Am J Hypertens. 2012;25(3):379-388. 2. Hundemer GL, Curhan GC, Yozamp N, Wang M, Vaidya A. Hypertension. 2018;72(3):658-666.3. Monticone S, D'Ascenzo F, Moretti C, et al. Lancet Diabetes Endocrinol. 2018;6(1):41-50. 4) Ferreira N, Tostes RC, Paradis P, Shiffrin E. Am J Hypertens. 2021, 34(1):15-27. 5.

In Obesity, via Visceral Adipocytes, Leads to Elevated Aldosterone Levels

Lorundrostat targets both the RAAS-dependent and -independent axes, providing a more complete solution to abnormally elevated aldosterone

Lorundrostat Is a Highly Selective, Potentially Best-in-Class ASI

Aldosterone Synthase Inhibitor Comparison Table

Lorundrostat

(Mineralys) LCI699 (Novartis)1

Baxdrostat (Astra Zeneca)2, 3

Vicadrostat

(Boehringer Ingelheim)4, 5

Selectivity

374X

3.6X

100X

250X

Half-life

10-12 hours

~4 hours

25-31 hours

4-5 hours

Reduction in PAC

40-70%

51-73%

27-44%

65%

Adrenal insufficiency or decrease in cortisol

no

yes

no

yes

Metabolism

Hepatic

Hepatic

Renal

n/a

Differentiated selectivity

Aldosterone inhibition with reduced risk of cortisol inhibition or off-target AEs

Optimal half-life

Aldosterone inhibition with rapid reversibility- essential for patients who may not tolerate a significant BP drop or are at risk for hyperkalemia, including patients with CKD

Information provided in the table above is for illustrative purposes only and no head-to-head clinical trials have been conducted evaluating these product candidates.

Differences exist between study or trial designs and subject characteristics, and caution should be exercised when comparing data across studies.

1. Schumacher CD, Steele RE, Brunner HR. J Hypertens. 2013;31(10):2085-2093. 2. Bogman K, Schwab D, Delporte ML, et al. Hypertension. 2017;69(1):189-196.

3. CinCor S1 filing 2020, 4. BI presentation at ASN 2023 5. Schulze, Schaible, et al Naunyn-Schmeideberg's Archives of Pharmacology.C

Comprehensive Clinical Plan Designed to Demonstrate Benefit in Two Distinct but Complementary Populations

"Real-World" setting in Launch-HTN and "Specialist" setting in Advance-HTN designed to demonstrate lorundrostat's clinical utility

"Real-World" Setting

(n=1,083)

PBO

PBO

50 to 100mg

Run-in

50mg

50 to 100mg

Washout

OLE

Wk 6 titration

Wk 4 titration

u/rHTN on existing AHTs (2-5), randomized 1-2-1, utilizing in-office

(AOBP) measure

u/rHTN on optimized AHA 2-3 drug regimen, randomized 1-1-1, utilizing 24hr ABPM,

AOBP, and in-home BP measure

Statistically Significant Outcomes in Both Pivotal Trial Primary Endpoints

Pivotal data for 50mg QD exceeds market expectations with efficacy and safety; BP reduction appears to increase from titration point to week 12

Week 6

Week 12

SBPChangeinmmHg

-10.0

-15.0

-20.0

-5.0

0.0

0

Absolute PBO-Adjusted

u/r/HTN patients on existing regimen of 2-5 AHTs

(n=1,083)

Week 4

Week 12

SBPChangeinmmHg

-5

-10

-15

-20

Absolute PBO-Adjusted

u/rHTN patients on optimized, AHA regimen

(n=285)

Equivalent Response Across Subgroups

Equivalent response demonstrated with lorundrostat across sex, race, BMI and in u/rHTN

Absolute and Placebo-Adjusted Change in SBP at

Week 6, pooled 50mg QD

(n=430 on 2 meds, n=648 on 3-5 meds)

2 Background

0

3-5 Background

Absolute and Placebo-Adjusted Change in SBP

Week 4, pooled 50mg QD

(n=177 on 2 meds, n=105 on 3 meds)

2 Background 3 Background ChangeinSBP(mmHg)

-10

-12

-14

-16

-18

-20

-2

-4

-6

-8

0

Absolute Placebo-Adjusted Change is SBP (mmHg)

-2

-4

ChangeinSBP(mmHg)

-6

-8

-10

-12

-14

-16

-18

-20

Absolute Placebo-Adjusted Change is SBP (mmHg)

10

Disclaimer

Mineralys Therapeutics Inc. published this content on April 01, 2025, and is solely responsible for the information contained herein. Distributed via , unedited and unaltered, on April 01, 2025 at 12:20 UTC.