Targeting Aldosterone in the
Treatment of Cardiorenal
Diseases
J u n e 2 0 2 4
Forward-Looking Statements and Market Data
We caution you that this presentation contains forward-looking statements. All statements other than statements of historical facts contained in this presentation, including statements regarding our future results of operations and financial position, business strategy, research and development plans, the anticipated timing, costs, design, and conduct of our ongoing and planned preclinical studies and planned clinical trials for lorundrostat and any future product candidates, the timing and likelihood of regulatory filings and approvals for lorundrostat and any future product candidates, our ability to commercialize our product candidates, if approved, the potential to develop future product candidates, the potential benefits of strategic collaborations and our intent to enter into any strategic arrangements, the timing and likelihood of success, and plans and objectives of management for future operations and future results of anticipated product development efforts, are forward-looking statements. In some cases, you can identify forward-looking statements by terms such as "may," "will," "should," "expect," "plan," "anticipate," "could," "intend," "target," "project," "contemplates," "believes," "estimates," "predicts," "potential" or "continue" or the negative of these terms or other similar expressions. The inclusion of forward-looking statements should not be regarded as a representation by us that any of our plans will be achieved. Actual results may differ from those set forth in this presentation due to the risks and uncertainties inherent in our business, including, without limitation: our future performance is dependent entirely on the success of lorundrostat; potential delays in the commencement, enrollment, and completion of clinical trials and nonclinical studies; our dependence on third parties in connection with manufacturing, research and clinical and nonclinical testing; unexpected adverse side effects or inadequate efficacy of lorundrostat that may limit its development, regulatory approval, and/or commercialization; unfavorable results from clinical trials and nonclinical studies; results of prior clinical trials and studies of lorundrostat are not necessarily predictive of future results; our reliance on our exclusive license with Mitsubishi Tanabe to provide us with intellectual property rights to develop and commercialize lorundrostat; our ability to obtain and maintain intellectual property protection for lorundrostat; we may use our capital resources sooner than we expect; our ability to maintain undisrupted business operations due to the COVID-19 pandemic or any other pandemic or future public health concerns; regulatory developments in the United States and foreign countries; and other risks described in our press releases and filings with the Securities and Exchange Commission (SEC), including under the heading "Risk Factors" in our Annual Report on Form 10-K for the year ended December 31, 2023. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date made, and except as required by applicable law, we do not plan to publicly update or revise any forward-looking statements contained herein, whether as a result of any new information, future events, changed circumstances or otherwise. All forward-looking statements are qualified in their entirety by this cautionary statement, which is made under the safe harbor provisions of the Private Securities Litigation Reform Act of 1995.
This presentation also contains estimates and other statistical data made by independent parties and by us relating to market size and growth and other data about our industry. This data involves a number of assumptions and limitations, and you are cautioned not to give undue weight to such estimates. In addition, projections, assumptions, and estimates of our future performance and the future performance of the markets in which we operate are necessarily subject to a high degree of uncertainty and risk. These and other factors could cause results to differ materially from those expressed in the estimates made by the independent parties and by us.
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Mineralys:
Targeting Aldosterone
in the Treatment
of Hypertension, CKD
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) 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 Q4 2024 and the second trial readout in 2H 2025
Proof-of-Concept CKD trial initiated 2H 2023 with readout in Q4 2024 to Q1 2025 creating a pipeline of disease opportunities
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Unmet Need in Both Hypertension and CKD Addressable by Lorundrostat
Significant overlap of hypertension, chronic kidney disease and obesity
CKD in the U.S.
Hypertension in the U.S.
115M Patients
60M Diagnosed
30M uncontrolled
CKD
~35M Patients
4M Diagnosed
Hypertension
~23M
Hypertension patients have comorbid CKD*
~50% prevalence of obesity in hypertension and CKD patients; respectively
- USRDS.org; High blood pressure redefined for first time in 14 years. American Heart Associate/American College of Cardiology Guidelines, retrieved from Heart.org; Chronic kidney disease in the general population (2010), retrieved from USRDS.org, accessed June 2022; Chronic kidney disease in the general population (2020), retrieved from USRDS.org, accessed June 2022
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Abnormally Elevated Aldosterone 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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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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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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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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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-BlindRun-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
-
± 0.98
81.5 ± 0.76
31.2 ± 0.41
- ± 1.3
39.3%
41.7%
46.6%
37.4%
3.1%
5.5%
2 medications = 52.8% / 3 or more medications = 47.2%
56.4%
77.9%
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Mineralys Therapeutics Inc. published this content on 10 June 2024 and is solely responsible for the information contained therein. Distributed by Public, unedited and unaltered, on 10 June 2024 20:05:07 UTC.