Mineralys Therapeutics : Corporate Overview January 2025

MLYS

Targeting Aldosterone in the

Treatment of Cardiorenal

Diseases

J a n u a r y 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, chronic kidney disease (CKD), obstructive sleep apnea (OSA) and heart failure

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

Proof-of-Concept trial demonstrated substantial overall BP reduction with once-daily dosing; enhanced response in obese subjects; well- tolerated with modest increase in potassium

Pivotal HTN program initiated in 2023 with first pivotal trial readout in March of 2025 and the second trial readout in mid first half 2025

Proof-of-Concept CKD and hypertension trial readout in 2Q 2025

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

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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

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4

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

DC

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.

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5

Prevalence of Elevated Aldosterone Linked to Rise in Obesity

As percent of population with obesity has risen in

the US, so has hyperaldosteronism

50%50%

Obesity in the US1

45%

40%

of Population

40%

35%

Hyperaldosteronism

30%30%

Percentage

25%

20%

20%

15%

Age >65 Years

10%

10%

5%

0%

0%

1950 1960 1970 1980 1990 2000 2010 2020 2030

BMI is significantly correlated with

aldosterone levels2

1. https://usafacts.org/articles/obesity-rate-nearly-triples-united-states-over-last-50-years. 2. Dudenbostel T, Ghazi L, Liu M, Li P, Oparil S, Calhoun DA. Hypertension. 2016;68(4):995-1003.

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Mineralys Therapeutics, Inc. ©2023. All Rights Reserved.

6

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

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Mineralys Therapeutics, Inc. ©2023. All Rights Reserved.

7

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

Aldosterone Synthase Inhibitor Comparison Table

Lorundrostat

LCI699

Baxdrostat

BI690517

(Mineralys)

(Novartis)1

(Astra Zeneca)2, 3

(Boehringer Ingelheim)4

Selectivity

374X

3.6X

100X

250X

Half-life

10-12 hours

~4 hours

25-31 hours

noted to be "short"

Reduction in PAC

65-70%

65-70%

65-70%

66%

Adrenal insufficiency

no

yes

no

yes

or decrease in cortisol

Metabolism

Hepatic

Hepatic

Renal

n/a

Best-in-class 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

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 meeting.

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8

Phase 2 Proof -of-Concept Study Design

Evaluating the safety, efficacy and dose-response of lorundrostat in uncontrolled and resistant hypertension

2-4 weeks

Pre-Screening

Part-1

PRA <1.0

N=180

Inclusion criteria:

BP >130/80 on >2 AHTs

eGFR >60

Part-2

PRA >1.0

N=36

2 weeks

Screening

Single-Blind Run-In

Background

Regimen of 2+

Medications

8 weeks

Double-Blind Treatment

Placebo QD N=30

lorundrostat 12.5 mg QD N=30

lorundrostat 50 mg QD N=30

lorundrostat 100 mg QD N=30

lorundrostat 12.5 mg BID N=30

lorundrostat 25 mg BID N=30

lorundrostat 100 mg QD N=30

& Placebo QD N=6

2-4 weeks

Washout

Primary efficacy endpoint:

Change in AOBP sysBP at 8 weeks compared to placebo

Key secondary endpoint:

ABPM measurement of average 24h and overnight BP

Randomization

Primary Efficacy and Safety

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Baseline Demographics and Disposition

90% of the randomized patients completed Part 1 of the Target-HTN trial

Category

Systolic BP (mm Hg)

Diastolic BP (mm Hg)

Body Mass Index (kg/m2)

Mean Baseline eGFR

Race % Black or African American

Sex % Male

Ethnicity % Hispanic or Latino

Diabetes

Heart Failure

Previous Myocardial Infarction

Number of Background Antihypertensive Medications

Use of Thiazide or Thiazide-like Diuretic

Use of ACE or ARB

Mean ± SEM of Baseline

2 medications = 52.8% / 3 or more medications = 47.2%

56.4%

77.9%

Confidential Property of Mineralys Therapeutics, Inc.

Mineralys Therapeutics, Inc. ©2023. All Rights Reserved.

10

Disclaimer

Mineralys Therapeutics Inc. published this content on January 08, 2025, and is solely responsible for the information contained herein. Distributed by Public, unedited and unaltered, on January 08, 2025 at 19:06:09.138.