Mineralys Therapeutics : Corporate Overview March 2025

Published: 2025-03-17 08:06:05 ET MLYS

Targeting Aldosterone in the

Treatment of Cardiorenal

Diseases

M a r c h 2 0 2 5

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

Lorundrostat is a highly selective ASI that reduces aldosterone ~70% with once-daily dosing

Launch-HTN: 19.0mmHg absolute and 11.7mmHg placebo-adjusted response with 50mg once daily at week 12 demonstrated the

meaningful clinical benefit, safety and tolerability in "real-world" patients

Advance-HTN: 7.9mmHg placebo adjusted reduction at 12 weeks demonstrated the meaningful clinical benefit, safety and tolerability confirmed HTN

Proof-of-Concept CKD and hypertension trial topline 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

CKD in the U.S.

u/rHTN &

HTN in the U.S.

Obesity

CKD / HTN

Endotype

Nephropathy

Obesity highly correlated to rHTN

Obesity link to dysregulated aldo

~20M u/rHTN patients

>25% in CV risk vs controlled HTN Kidney injury link to hyper-perfusion ~23M HTN + CKD patients

OSA in the U.S.

OSA /

Nighttime BP link to CV risk

Nocturnal

70-80% prevalence of rHTN in OSA

HTN

~24M Moderate-to-Severe OSA

Abnormally Elevated Aldosterone Impacts Multiple Biological Pathways and Is a Key Driver in Multiple Cardiorenal Diseases

Genomic Effects

(mineralocorticoid receptor)

Na+ and water retention drives blood volume and blood pressure

ALDOSTERONE

Non-Genomic Effects

(GPR30 receptor)

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

Aldosterone-driven Cardiorenal Disorders

T-cell

M⍬

Vascular and systemic

Inflammation 4

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

RAAS-dependent Axis

RAAS-independent Axis

Blocks RAAS-dependent

Lorundrostat

ACEI

ARBs

Renin

Blocks

RAAS-independent

Lorundrostat

Adipocytes

- Angiotensin

Aldosterone

Adipokines

Leptin, other

Aldosterone

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

ASI

Aldosterone Synthase Inhibitor Comparison Table

Lorundrostat

LCI699

Baxdrostat

Vicadrostat

(Mineralys)

(Novartis)1

(Astra Zeneca)2, 3

(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

65-70%

66%

Adrenal insufficiency

yes

or decrease in cortisol

Metabolism

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.

Lorundrostat Demonstrated Consistent Clinical Profile

Across Three Distinct Trials All in Uncontrolled and

Resistant Hypertension

Demonstrated

safety and efficacy

efficacy and safety

efficacy and safety in

n=200

in confirmed u/rHTN

largest ever ASI trial

n=285

in HTN

n=1,083

Full Data, September 2023

Topline Data, March 2025

Launch-HTN Phase 3 Pivotal Trial Design

Real-World efficacy and safety trial of lorundrostat when added on top of 2-5 existing hypertension medications in uncontrolled and resistant hypertension, 1,083 subjects

2 weeks

12 weeks

Placebo Run-In

Double-Blind Treatment

Existing background antihypertensive treatment (2 to 5 meds)

Placebo QD

Fail to achieve

goal with AOBP on

Lorundrostat 50 mg QD

existing regimen

Lorundrostat 50 mg QD titrate to 100 mg QD

Up-titration @

week 6

if SBP ≥ 130 mmHg

End of Study

Primary efficacy

endpoint

Change from baseline in AOBP Sys BP at Week 6

Launch-HTN Significant Benefit in "Real World" Patients

Real-World study, how practitioners would utilize lorundrostat in daily practice for uHTN and rHTN

SBP Change in mmHg

Week 6

Week 12

0.0

Primary

Predefined

Endpoint

-5.0

-9.1

-10.0

-11.7

(p<0.0001)

-15.0

-16.9

-19.0

-20.0

u/r/HTN patients on existing regimen of 2-5 AHTs (n=1,083)

50 mg lorundrostat once-daily dose confirmed

Safe and well tolerated

Hyperkalemia rate above 6.0

mmol/L of 1.1% and 1.5%, in 50mg

and 50mg to 100mg arms,

respectively

Absolute PBO-Adjusted

Disclaimer

Mineralys Therapeutics Inc. published this content on March 17, 2025, and is solely responsible for the information contained therein. Distributed by Public, unedited and unaltered, on March 17, 2025 at 12:05:06.617.