Group 1 - Investors in the biotechnology sector have seen significant stock price increases, with Nektar Therapeutics and Mineralys Therapeutics both experiencing over 100% gains in the month leading up to September 19 [1] - Nektar Therapeutics' stock surged 108% from August 18 to September 18, driven by positive investor sentiment regarding its lead candidate, rezpegaldesleukin, an IL-2 pathway agonist [3][4] - In a phase 2b study for moderate to severe eczema, the highest dose of rezpegaldesleukin showed a 30% placebo-adjusted improvement, indicating potential competition with Dupixent, which generated $14.2 billion in sales last year [4][5] Group 2 - In the Rezolve-AD trial, 42% of patients achieved 75% skin clearance with rezpegaldesleukin compared to 17% in the placebo group, and in a longer treatment duration group, 62% achieved the same result [5][6] - Nektar Therapeutics currently has a market cap of $989 million, which is considered low for a company with a potential blockbuster treatment in mid-stage trials, although it has no products on the market [7] - A successful phase 3 trial for rezpegaldesleukin could significantly increase Nektar's stock value, but the company has not yet initiated a phase 3 program [9]

Core Viewpoint - Momentum investing focuses on following a stock's recent price trends, aiming to buy high and sell higher, with the expectation that established trends will continue [1] Company Overview: Mineralys Therapeutics, Inc. (MLYS) - MLYS currently holds a Momentum Style Score of A, indicating strong momentum characteristics [2] - The company has a Zacks Rank of 2 (Buy), suggesting a favorable outlook compared to the market [3] Performance Metrics - MLYS shares have increased by 124.81% over the past week, significantly outperforming the Zacks Medical - Biomedical and Genetics industry, which rose by 1.17% [5] - Over the past month, MLYS's price change is 172.4%, while the industry only saw a 4.66% increase [5] - In the last three months, MLYS shares rose by 167.14%, and over the past year, they increased by 203.46%, compared to the S&P 500's gains of 8.64% and 21.49%, respectively [6] Trading Volume - MLYS has an average 20-day trading volume of 2,452,919 shares, which is considered a bullish indicator when combined with rising stock prices [7] Earnings Outlook - In the past two months, four earnings estimates for MLYS have been revised upwards, while none have been lowered, leading to an increase in the consensus estimate from -$3.31 to -$2.83 [9] - For the next fiscal year, three estimates have also moved upwards with no downward revisions [9] Conclusion - Given the strong performance metrics and positive earnings outlook, MLYS is positioned as a promising investment opportunity with a Momentum Score of A [11]

Core Viewpoint - The healthcare sector is experiencing significant stock price increases, with some stocks more than doubling in value since the end of July, indicating potential for further gains despite recent surges [1][2]. Group 1: Precigen - Precigen's shares increased by 155% from the end of July to September 5, following FDA approval for its first treatment, Papzimeos, which is aimed at recurrent respiratory papillomatosis (RRP) [4][5]. - Papzimeos is the first and only FDA-approved treatment for approximately 27,000 patients with RRP, with a notable response rate in clinical trials where 18 out of 35 patients avoided surgery for at least 12 months post-treatment [5][6]. - Analysts, including Swayampakula Ramakanth from HC Wainwright, have set a price target of $8.50 for Precigen, suggesting a potential 95% increase in the next year [6]. Group 2: Mineralys Therapeutics - Mineralys Therapeutics saw a 146% rise in stock price from the end of July to September 5, driven by a successful funding round for the development of its lead candidate, lorundrostat [7][8]. - The company raised $287.5 million through a secondary offering, which followed the suspension of an at-the-money equity offering [8]. - In a phase 3 trial, lorundrostat demonstrated a significant reduction in systolic pressure, outperforming a placebo [9]. - Following AstraZeneca's less favorable data for a competing product, Bank of America analyst Greg Harrison raised the target price for Mineralys to $43 per share, indicating a potential 24% gain [11]. - Despite the positive outlook, the company ended June with $325 million in cash, sufficient to last until 2027, raising concerns about the urgency of submitting for approval [12]. - Mineralys has a market cap of $2.7 billion, which could be affected by the timing of lorundrostat's approval compared to competitors [14]. Group 3: Market Potential - Precigen's market cap is approximately $1.3 billion, with expectations for Papzimeos potentially underestimated, as it is set to launch in a niche market without competition [15]. - Papzimeos could generate over $1 billion in annual sales at peak pricing, with a list price exceeding $200,000 per patient per year [16].

Core Insights - The Launch-HTN trial of lorundrostat, a novel aldosterone synthase inhibitor, shows significant blood pressure reductions in diverse high-risk patient populations with uncontrolled hypertension [1][2][3] - The trial enrolled 1,083 participants, making it the largest global Phase 3 trial for uncontrolled or resistant hypertension [6][12] - Lorundrostat demonstrated a favorable safety and tolerability profile, with no new safety signals observed [5][8] Company Overview - Mineralys Therapeutics, Inc. is a clinical-stage biopharmaceutical company focused on developing treatments for hypertension and related conditions driven by dysregulated aldosterone [1][15] - The company plans to file a New Drug Application (NDA) for lorundrostat in late 2025 or early 2026 [9] Trial Details - The Launch-HTN trial utilized automated office blood pressure measurements and allowed participants to continue existing antihypertensive medications [6][12] - Key demographics of the trial included 29% Black/African American participants, 41% aged 65 or older, and 63% with obesity [2][3] Efficacy Results - Lorundrostat 50 mg showed statistically significant reductions in blood pressure across various subgroups, including a 16.9 mmHg reduction at Week 6 and a 19.0 mmHg reduction at Week 12 [7][12] - The trial results indicated consistent blood pressure lowering effects across high-risk subgroups, addressing a critical unmet medical need [3][4] Safety Profile - The safety outcomes were favorable, with adverse events generally mild or moderate, and a very low incidence of serious drug-related adverse events [5][8] - No significant suppression of cortisol production was observed, and electrolyte changes were modest and reversible [8] Market Context - Hypertension is a leading modifiable risk factor for cardiovascular disease, contributing to over 685,000 deaths in the U.S. in 2022 [10] - Less than 50% of hypertension patients achieve their blood pressure goals with current medications, highlighting the need for new treatments like lorundrostat [11]

Core Insights - The Launch-HTN trial of lorundrostat, a novel aldosterone synthase inhibitor, shows significant blood pressure reductions in diverse high-risk populations with uncontrolled hypertension [1][2][3] - The trial enrolled 1,083 participants, making it the largest global Phase 3 trial for uncontrolled or resistant hypertension [7] - Lorundrostat demonstrated a favorable safety and tolerability profile, with no new safety signals observed [6][9] Company Overview - Mineralys Therapeutics, Inc. is a clinical-stage biopharmaceutical company focused on developing treatments for hypertension and related conditions driven by dysregulated aldosterone [1][15] - The company plans to file a New Drug Application (NDA) for lorundrostat in late 2025 or early 2026 [10] Trial Details - The Launch-HTN trial utilized automated office blood pressure measurements and allowed participants to continue existing antihypertensive medications [7][12] - Key demographics included 29% Black/African American, 41% aged 65 or older, and 63% with obesity [2][3] Efficacy Results - Lorundrostat 50 mg showed consistent, statistically significant reductions in blood pressure across various subgroups, including a 16.9 mmHg reduction at Week 6 [8][4] - The trial results indicated that lorundrostat could address critical unmet medical needs in high-risk patient cohorts [3][4] Safety Profile - The safety outcomes were favorable, with adverse events generally mild or moderate, and no significant new safety concerns identified [6][9] - The incidence of serious adverse events leading to discontinuation was very low [9] Future Directions - Mineralys is moving forward with its NDA filing strategy and has scheduled a pre-NDA meeting with the FDA [10] - The company aims to evaluate lorundrostat for potential treatment of chronic kidney disease and obstructive sleep apnea in addition to hypertension [13][15]

Core Viewpoint - Mineralys Therapeutics, Inc. has successfully closed a public offering of 11,274,509 shares of common stock, raising approximately $287.5 million before expenses, to fund the development of its product candidate lorundrostat and for general corporate purposes [1][2]. Group 1: Offering Details - The public offering price was set at $25.50 per share, which included the full exercise of the underwriters' option to purchase an additional 1,470,588 shares [1]. - The offering was managed by BofA Securities, Evercore ISI, Goldman Sachs & Co. LLC, Stifel, and Wells Fargo Securities, with LifeSci Capital as the lead manager [2]. Group 2: Use of Proceeds - The net proceeds from the offering will be utilized for clinical development of lorundrostat, including research, development, manufacturing, and pre-commercialization activities, as well as for working capital and general corporate purposes [2]. Group 3: Company Overview - Mineralys Therapeutics is a clinical-stage biopharmaceutical company focused on developing treatments for hypertension and related comorbidities, including chronic kidney disease and obstructive sleep apnea, driven by dysregulated aldosterone [5]. - The company's initial product candidate, lorundrostat, is a proprietary, orally administered, highly selective aldosterone synthase inhibitor [5].

Core Viewpoint - Mineralys Therapeutics, Inc. has announced an upsized underwritten public offering of 9,803,921 shares at a price of $25.50 per share, aiming to raise approximately $250 million before expenses [1][3]. Group 1: Offering Details - The public offering consists of 9,803,921 shares priced at $25.50 each, with expected gross proceeds of around $250 million [1]. - Mineralys has granted underwriters a 30-day option to purchase an additional 1,470,588 shares [1]. - The offering is anticipated to close on or about September 4, 2025, pending customary closing conditions [1]. Group 2: Use of Proceeds - The net proceeds from the offering will be utilized for the clinical development of lorundrostat, including research, development, manufacturing, and pre-commercialization activities, as well as for working capital and general corporate purposes [3]. Group 3: Underwriters - BofA Securities, Evercore ISI, Goldman Sachs & Co. LLC, Stifel, and Wells Fargo Securities are serving as joint book-running managers for the offering [2]. - LifeSci Capital is acting as the lead manager, while H.C. Wainwright & Co. is the co-manager for the offering [2]. Group 4: Company Overview - Mineralys Therapeutics is a clinical-stage biopharmaceutical company focused on developing treatments for hypertension and related comorbidities, including chronic kidney disease and obstructive sleep apnea [6]. - The company's lead product candidate, lorundrostat, is a proprietary, orally administered, highly selective aldosterone synthase inhibitor [6].

Core Viewpoint - Mineralys Therapeutics, Inc. (MLYS) has seen a 2% increase in share price over the past four weeks, closing at $14.52, with a potential upside of 149.7% based on Wall Street analysts' mean price target of $36.25 [1] Price Targets - The average price target consists of eight estimates ranging from a low of $15.00 to a high of $48.00, with a standard deviation of $11.25, indicating variability among analysts [2] - The lowest estimate suggests a 3.3% increase from the current price, while the highest estimate indicates a 230.6% upside [2] Analyst Sentiment - There is strong agreement among analysts regarding MLYS's ability to report better earnings than previously predicted, which supports the potential for stock upside [4] - Recent trends show that four earnings estimates have been revised higher in the last 30 days, with no negative revisions, leading to a 10.2% increase in the Zacks Consensus Estimate [12] Zacks Rank - MLYS holds a Zacks Rank 2 (Buy), placing it in the top 20% of over 4,000 ranked stocks based on earnings estimate factors, indicating a strong potential for upside [13] Conclusion on Price Targets - While the consensus price target may not be a reliable indicator of the extent of MLYS's potential gains, it does provide a useful guide for the direction of price movement [14]

Financial Data and Key Metrics Changes - The company ended Q2 2025 with cash, cash equivalents, and investments of $324.9 million, up from $198.2 million as of December 31, 2024, indicating a significant increase in liquidity [14] - R&D expenses for Q2 2025 were $38.3 million, a slight decrease from $39.3 million in Q2 2024, primarily due to reduced preclinical and clinical costs [15] - G&A expenses increased to $8.5 million in Q2 2025 from $5.9 million in Q2 2024, driven by higher compensation and professional fees [16] - The net loss for Q2 2025 was $43.3 million, compared to $41.0 million in Q2 2024, reflecting increased expenses [17] Business Line Data and Key Metrics Changes - The company is focused on developing aldosterone synthase inhibitors (ASIs) for hypertension and related conditions, with promising clinical data from trials such as LAUNCH HTN and ADVANCE HTN [6][10] - A survey indicated that 95% of clinicians would likely prescribe lorundrostat if approved, highlighting strong interest in the product [7] Market Data and Key Metrics Changes - Uncontrolled and resistant hypertension affects over 20 million patients in the U.S., representing a significant unmet medical need [8] - The company has identified nearly 9 million patients who started new treatments in the third line or later position in 2024, reflecting dissatisfaction with current options [7] Company Strategy and Development Direction - The company aims to enhance the profile of lorundrostat in treating hypertension with comorbid conditions like chronic kidney disease (CKD) and obstructive sleep apnea (OSA) [10][12] - A pre-NDA meeting with the FDA is scheduled for 2025, indicating progress towards regulatory approval [13] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the clinical data supporting lorundrostat's efficacy and safety, emphasizing the unmet need in the market [21][34] - The company is exploring partnership opportunities, particularly outside the U.S., to maximize the reach of lorundrostat [24] Other Important Information - The company is expanding its medical communications team to raise awareness and interest in lorundrostat ahead of its potential launch [9] - The EXPLORER OSA trial is expected to provide top-line data in 2026, focusing on the effects of lorundrostat on nighttime blood pressure [12] Q&A Session Summary Question: Thoughts on AstraZeneca's Phase III Vax HTN data - Management refrained from speculating on AstraZeneca's data but expressed confidence in lorundrostat's safety and efficacy based on their own trials [21][22] Question: Opportunities for lorundrostat beyond hypertension - Management indicated potential for lorundrostat in treating related comorbidities like CKD and OSA, emphasizing its role in managing dysregulated aldosterone [30] Question: Payer strategies and market access - Management does not anticipate a step edit through spironolactone, expecting payers to navigate access through generic classes instead [55] Question: Commercial strategy and market entry - The company is currently focused on payer strategy and medical affairs to build awareness for lorundrostat, with specific commercial strategies still in development [59][60] Question: Pre-NDA meeting expectations - Management is confident in the comprehensive data package prepared for the FDA, which includes insights from various clinical trials [62] Question: Concerns about drug-drug interactions - Management clarified that PPI use is allowed in trials, and the focus is on ensuring adequate blood pressure control rather than safety concerns [41] Question: Future data releases from ongoing trials - Management confirmed plans to publish data from the open-label extension trial, TRANSFORM HDN, as it becomes available [74]

[Part I - Financial Information](index=4&type=section&id=Part%20I%20-%20Financial%20Information) [Item 1. Financial Statements](index=4&type=section&id=Item%201.%20Financial%20Statements) This section presents Mineralys Therapeutics, Inc.'s unaudited condensed financial statements and related notes for periods ended June 30, 2025, and December 31, 2024 [Condensed Balance Sheets](index=4&type=section&id=Condensed%20Balance%20Sheets) | Metric | June 30, 2025 (in thousands) | December 31, 2024 (in thousands) | | :----------------------------- | :----------------------------- | :----------------------------- | | Cash and cash equivalents | $101,788 | $114,091 | | Investments | $223,128 | $84,096 | | Total current assets | $335,269 | $205,351 | | Total assets | $335,724 | $205,903 | | Total current liabilities | $22,173 | $14,646 | | Total stockholders' equity | $313,551 | $191,257 | [Condensed Statements of Operations](index=5&type=section&id=Condensed%20Statements%20of%20Operations) | Metric (in thousands) | Three Months Ended June 30, 2025 | Three Months Ended June 30, 2024 | Six Months Ended June 30, 2025 | Six Months Ended June 30, 2024 | | :-------------------- | :------------------------------- | :------------------------------- | :----------------------------- | :----------------------------- | | Research and development | $38,278 | $39,273 | $76,157 | $70,027 | | General and administrative | $8,468 | $5,895 | $15,036 | $10,503 | | Total operating expenses | $46,746 | $45,168 | $91,193 | $80,530 | | Net loss | $(43,274) | $(41,014) | $(85,485) | $(72,522) | | Net loss per share (basic and diluted) | $(0.66) | $(0.83) | $(1.44) | $(1.54) | [Condensed Statements of Stockholders' Equity](index=6&type=section&id=Condensed%20Statements%20of%20Stockholders%27%20Equity) | Metric (in thousands) | Balance as of December 31, 2024 | Balance as of June 30, 2025 | | :-------------------- | :------------------------------ | :-------------------------- | | Common Stock (Shares) | 49,821,915 | 65,725,409 |\ | Common Stock (Amount) | $5 | $6 |\ | Additional Paid-In Capital | $493,770 | $701,548 |\ | Accumulated Deficit | $(302,518) | $(388,003) |\ | Total Stockholders' Equity | $191,257 | $313,551 | - Issuance of common stock in a public offering, net of **$12.5 million** in offering costs, increased total stockholders' equity by **$188.7 million** for the six months ended June 30, 2025[16](index=16&type=chunk) - Issuance of common stock under the ATM Agreement, net of **$46 thousand** in issuance costs, contributed **$9.5 million** to total stockholders' equity for the six months ended June 30, 2025[16](index=16&type=chunk) [Condensed Statements of Cash Flows](index=8&type=section&id=Condensed%20Statements%20of%20Cash%20Flows) | Cash Flow Activity (in thousands) | Six Months Ended June 30, 2025 | Six Months Ended June 30, 2024 | | :-------------------------------- | :----------------------------- | :----------------------------- | | Net cash used in operating activities | $(75,656) | $(49,285) | | Net cash used in investing activities | $(135,757) | $(48,216) | | Net cash provided by financing activities | $199,110 | $116,053 | | Net increase (decrease) in cash and cash equivalents | $(12,303) | $18,552 | | Cash and cash equivalents - ending | $101,788 | $67,856 | [Notes to Condensed Financial Statements](index=9&type=section&id=Notes%20to%20Condensed%20Financial%20Statements) [Note 1. Nature of Business](index=9&type=section&id=Note%201.%20Nature%20of%20Business) - Mineralys Therapeutics, Inc. is a clinical-stage biopharmaceutical company developing lorundrostat for cardiorenal conditions driven by dysregulated aldosterone[22](index=22&type=chunk) - The company has not generated revenue, incurred significant operating losses, and reported an accumulated deficit of **$388.0 million** as of June 30, 2025, with **$324.9 million** in cash, cash equivalents, and investments[23](index=23&type=chunk) - Operations are expected to be funded for at least twelve months from June 30, 2025, through equity offerings, debt financings, or strategic collaborations[24](index=24&type=chunk) [Note 2. Summary of Significant Accounting Policies](index=9&type=section&id=Note%202.%20Summary%20of%20Significant%20Accounting%20Policies) - The unaudited condensed financial statements adhere to U.S. GAAP and SEC interim reporting rules, with certain footnotes condensed or omitted[25](index=25&type=chunk) - The Company operates in a single segment, with the CEO evaluating performance based on net loss and functional expenses[28](index=28&type=chunk) - The Company utilizes the Black-Scholes option pricing model for stock option awards, recognizing stock-based compensation expense straight-line over the service period[42](index=42&type=chunk)[47](index=47&type=chunk) | Item | June 30, 2025 | December 31, 2024 | | :-------------------------- | :------------ | :-------------- | | Cash | $1,009 | $664 | | Cash equivalents | $100,779 | $113,427 | | Total cash and cash equivalents | $101,788 | $114,091 | [Note 3. Fair Value of Financial Instruments](index=13&type=section&id=Note%203.%20Fair%20Value%20of%20Financial%20Instruments) | Asset (in thousands) | June 30, 2025 (Level 1) | December 31, 2024 (Level 1) | | :------------------- | :---------------------- | :-------------------------- | | Money market funds | $95,818 | $83,602 | | U.S. Treasury Bills (in thousands) | Original Maturities | Amortized Cost (June 30, 2025) | Estimated Fair Value (June 30, 2025) | Amortized Cost (Dec 31, 2024) | Estimated Fair Value (Dec 31, 2024) | | :--------------------------------- | :------------------ | :----------------------------- | :----------------------------------- | :---------------------------- | :---------------------------------- | | Cash and cash equivalents | less than 3 months | $4,961 | $4,961 | $29,825 | $29,829 | | Investments | between 3 and 12 months | $223,128 | $223,085 | $84,096 | $84,123 | | Total | | $228,089 | $228,046 | $113,921 | $113,952 | [Note 4. Commitments and Contingencies](index=14&type=section&id=Note%204.%20Commitments%20and%20Contingencies) - The Company's license agreement with Mitsubishi Tanabe for lorundrostat includes potential commercial milestone payments up to **$155.0 million** and tiered royalties (**mid-single-digits to 10%**) on net sales[59](index=59&type=chunk) - No remaining development milestone obligations or related expenses were incurred under the Mitsubishi License for the three or six months ended June 30, 2025, and 2024[61](index=61&type=chunk) - The Company is not currently subject to any material legal proceedings or claims under indemnification agreements[64](index=64&type=chunk)[65](index=65&type=chunk) [Note 5. Accrued Liabilities](index=16&type=section&id=Note%205.%20Accrued%20Liabilities) | Accrued Liability (in thousands) | June 30, 2025 | December 31, 2024 | | :------------------------------- | :------------ | :---------------- | | Research and development expenses | $14,656 | $8,614 | | Compensation and benefits | $2,623 | $3,582 | | Professional fees and other | $1,730 | $1,971 | | Total | $19,009 | $14,167 | [Note 6. Capital Stock](index=16&type=section&id=Note%206.%20Capital%20Stock) - As of June 30, 2025, the Company had **500 million** authorized common shares and **50 million** authorized undesignated preferred shares[68](index=68&type=chunk) - In March 2025, a public offering of **14,907,406** common shares at **$13.50** per share generated approximately **$188.7 million** in net proceeds for clinical development and general corporate purposes[69](index=69&type=chunk) - Under an ATM Agreement, **674,518** shares were sold from April to June 2025 for **$9.5 million** in net proceeds, with **$90.5 million** of ATM Shares remaining available as of June 30, 2025[72](index=72&type=chunk) - In February 2024, a private placement of common stock and pre-funded warrants generated approximately **$116.1 million** in net proceeds, primarily for lorundrostat R&D and working capital[73](index=73&type=chunk) [Note 7. Stock-Based Compensation](index=17&type=section&id=Note%207.%20Stock-Based%20Compensation) - The 2023 Incentive Award Plan allows for various stock-based awards, with **1,761,818** shares available for grant as of June 30, 2025[76](index=76&type=chunk)[83](index=83&type=chunk) - The 2025 Employment Inducement Incentive Award Plan, effective February 10, 2025, reserved **1 million** shares for new employee inducement awards, with no shares issued as of August 12, 2025[80](index=80&type=chunk) | Stock-Based Compensation Expense (in thousands) | Three Months Ended June 30, 2025 | Three Months Ended June 30, 2024 | Six Months Ended June 30, 2025 | Six Months Ended June 30, 2024 | | :---------------------------------------------- | :------------------------------- | :------------------------------- | :----------------------------- | :----------------------------- | | Research and development | $1,943 | $1,281 | $3,571 | $2,246 | | General and administrative | $2,610 | $1,591 | $4,627 | $2,817 | | Total | $4,553 | $2,872 | $8,198 | $5,063 | [Item 2. Management's Discussion and Analysis of Financial Condition and Results of Operations](index=20&type=section&id=Item%202.%20Management%27s%20Discussion%20and%20Analysis%20of%20Financial%20Condition%20and%20Results%20of%20Operations) This section analyzes Mineralys Therapeutics, Inc.'s financial condition and results of operations, including clinical trial results and liquidity, for periods ended June 30, 2025, and 2024 [Overview](index=21&type=section&id=Overview) - Mineralys Therapeutics is a clinical-stage biopharmaceutical company developing lorundrostat for cardiorenal conditions such as hypertension, CKD, and OSA[95](index=95&type=chunk) - Over half of the **120 million** U.S. hypertension patients fail to achieve BP goals, with dysregulated aldosterone affecting approximately **30%** of these patients[95](index=95&type=chunk) - Positive results from pivotal trials (Advance-HTN, Launch-HTN) and the Phase 2 Explore-CKD trial for lorundrostat demonstrated efficacy and a favorable safety profile in H1 2025[96](index=96&type=chunk) [Clinical Program Highlights](index=21&type=section&id=Clinical%20Program%20Highlights) - Pivotal trials Launch-HTN and Advance-HTN for uncontrolled or resistant hypertension achieved statistically significant and clinically meaningful primary efficacy endpoints with a favorable safety profile[97](index=97&type=chunk) - The company plans a pre-NDA meeting with the FDA in **Q4 2025** for lorundrostat in uncontrolled/resistant hypertension[97](index=97&type=chunk) - Positive topline data from the Phase 2 Explore-CKD trial for lorundrostat in hypertensive participants with comorbid CKD showed high statistical significance and clinical meaningfulness in June 2025[98](index=98&type=chunk) - The FDA cleared an investigational new drug application for Explore-OSA in January 2025, with topline results for this Phase 2 trial anticipated in **H1 2026**[101](index=101&type=chunk) [Pivotal Program Clinical Trial Results](index=22&type=section&id=Pivotal%20Program%20Clinical%20Trial%20Results) [Efficacy Results](index=22&type=section&id=Efficacy%20Results) **Launch-HTN Phase 3 Trial (automated office systolic BP measure, n=1,083 randomized):** | Metric | Week 6 (50 mg pooled) Absolute Reduction | Week 6 (50 mg pooled) Placebo-Adjusted Reduction | Week 12 Absolute Reduction | Week 12 Placebo-Adjusted Reduction | | :----- | :--------------------------------------- | :----------------------------------------------- | :------------------------- | :--------------------------------- | | 50 mg | -16.9 mmHg | -9.1 mmHg (p<0.0001)* | -19.0 mmHg | -11.6 mmHg (p<0.0001) | | 50 to 100 mg | | | -15.7 mmHg | -8.4 mmHg (p=0.0016) | * Primary endpoint **Advance-HTN Phase 2 Trial (24-hour ambulatory systolic BP, n=285 randomized):** | Metric | Week 4 (50 mg pooled) Absolute Reduction | Week 4 (50 mg pooled) Placebo-Adjusted Reduction | Week 12 Absolute Reduction | Week 12 Placebo-Adjusted Reduction* | | :----- | :--------------------------------------- | :----------------------------------------------- | :------------------------- | :---------------------------------- | | 50 mg | -11.5 mmHg | -5.3 mmHg (p=0.0006) | -15.4 mmHg | -7.9 mmHg (p=0.001) | | 50 to 100 mg | | | -13.9 mmHg | -6.5 mmHg (p=0.006) | * Primary endpoint [Safety and Tolerability Results](index=23&type=section&id=Safety%20and%20Tolerability%20Results) - Clinical safety findings in Launch-HTN and Advance-HTN, including adrenocorticotropic hormone-stimulated and serum cortisol, serum potassium, serum sodium, and eGFR, support a favorable benefit-risk profile for lorundrostat[108](index=108&type=chunk) - In Launch-HTN, confirmed hyperkalemia incidence was **0.6%** (50 mg arm) and **1.1%** (50 to 100 mg arm) after excluding spurious results[109](index=109&type=chunk) - In Advance-HTN, confirmed hyperkalemia incidence was **2.1%** (50 mg arm) and **3.2%** (50 to 100 mg arm) after excluding spurious results[111](index=111&type=chunk) [Explore-CKD Clinical Trial Results](index=24&type=section&id=Explore-CKD%20Clinical%20Trial%20Results) **Explore-CKD Phase 2 Trial (N=59):** | Metric | Placebo | Lorundrostat 25 mg | Placebo-Adjusted | | :------------------------------------ | :------ | :----------------- | :--------------- | | Change in systolic BP (mmHg)* | -1.76 | -9.25 | -7.5 (p=0.0024) | | Change in spot UACR (mg/g) | -6.60% | -30.51% | -25.60% (p=0.0015) | | Change in eGFR** (mL/min/1.73m ) | -2.20% | -6.78% | -4.58% (p=0.0362) | | TEAEs leading to discontinuation of study drug | 1/57 (2%) | 2/58 (3%) | | | Confirmed hyperkalemia*** (K + >6.0 mmol/L) | 0/59 (0%) | 3/58 (5%) | | * Primary endpoint. ** Cystatin-C formula. *** Per protocol Systolic BP, UACR, and eGFR estimates and p values from Mixed Effects Model for a crossover trial with multiple baselines. - The Explore-CKD trial demonstrated highly statistically significant and clinically meaningful reductions in systolic BP and UACR, with a favorable safety and tolerability profile[112](index=112&type=chunk) - A modest, anticipated decrease in mean eGFR (**-4.6%** placebo-adjusted) was observed during lorundrostat treatment, consistent with other RAAS inhibitors[116](index=116&type=chunk) [Financial Overview](index=25&type=section&id=Financial%20Overview) - Since inception in May 2019, the Company has focused on business planning, capital raising, in-licensing lorundrostat, and R&D, incurring net losses and no product sales revenue[119](index=119&type=chunk)[120](index=120&type=chunk) | Metric (in millions) | June 30, 2025 | December 31, 2024 | | :------------------- | :------------ | :---------------- | | Cash, cash equivalents, and investments | $324.9 | | | Accumulated deficit | $388.0 | $302.5 | | Net loss (six months) | $85.5 | $72.5 | - The Company believes current cash, cash equivalents, and investments are sufficient to fund operations for at least twelve months, but anticipates substantial increases in expenses and operating losses due to ongoing clinical trials and regulatory activities[120](index=120&type=chunk)[121](index=121&type=chunk) [License Agreement with Mitsubishi Tanabe](index=26&type=section&id=License%20Agreement%20with%20Mitsubishi%20Tanabe) - The Company holds an exclusive, worldwide license from Mitsubishi Tanabe for lorundrostat, with remaining obligations for commercial milestone payments up to **$155.0 million** and tiered royalties (**mid-single-digits to 10%**) on net sales[122](index=122&type=chunk) - The Company is obligated to use commercially reasonable efforts to develop and seek regulatory approval for lorundrostat in major markets[123](index=123&type=chunk) [Public Offering](index=26&type=section&id=Public%20Offering) - In March 2025, the Company issued **14,907,406** common shares at **$13.50** per share, generating approximately **$188.7 million** in net proceeds[124](index=124&type=chunk) - Proceeds from the public offering are allocated to fund clinical development of lorundrostat (R&D, manufacturing, pre-commercialization), working capital, and general corporate purposes[124](index=124&type=chunk) [At Market Equity Offering Sales Agreement](index=26&type=section&id=At%20Market%20Equity%20Offering%20Sales%20Agreement) - Under an ATM Agreement established in March 2024, the Company can sell up to **$100.0 million** of common stock through sales agents[125](index=125&type=chunk) - From April to June 30, 2025, **674,518** ATM Shares were sold at a weighted-average price of **$14.15** per share, yielding approximately **$9.5 million** in net proceeds[126](index=126&type=chunk) - As of June 30, 2025, approximately **$90.5 million** of ATM Shares remained available for sale, with an additional **$7.9 million** in net proceeds from sales through August 12, 2025[126](index=126&type=chunk) [Private Placement Offering](index=27&type=section&id=Private%20Placement%20Offering) - In February 2024, a private placement of **8,339,169** common shares and **549,755** pre-funded warrants generated approximately **$116.1 million** in aggregate net proceeds[127](index=127&type=chunk) - Net proceeds from the private placement fund lorundrostat research and development and general working capital[127](index=127&type=chunk) - Pre-funded warrants are immediately exercisable at **$0.001** per share, with beneficial ownership limitations of **4.99%**, **9.99%**, or **19.99%** as selected by the holder[128](index=128&type=chunk) [Key Components of Results of Operations](index=27&type=section&id=Key%20Components%20of%20Results%20of%20Operations) [Operating Expenses](index=27&type=section&id=Operating%20Expenses) [Research and Development](index=27&type=section&id=Research%20and%20Development) - R&D expenses primarily include external costs (CROs, consultants, manufacturing for clinical trials) and internal costs (personnel-related expenses, stock-based compensation)[130](index=130&type=chunk)[132](index=132&type=chunk) - R&D expenses are expected to increase substantially due to ongoing and planned clinical trials, regulatory approvals, and commercial readiness activities for lorundrostat[131](index=131&type=chunk)[132](index=132&type=chunk) - Future development costs are highly variable, depending on trial scope, regulatory feedback, manufacturing costs, and potential collaborations[131](index=131&type=chunk)[133](index=133&type=chunk) [General and Administrative Expenses](index=29&type=section&id=General%20and%20Administrative%20Expenses) - G&A expenses primarily consist of personnel-related costs (salaries, bonuses, stock-based compensation) for executive and administrative functions, along with legal, accounting, and consulting fees[134](index=134&type=chunk) - G&A expenses are expected to increase to support expanded R&D and manufacturing activities, and public company operating costs, including additional personnel and compliance[134](index=134&type=chunk) [Other Income, Net](index=29&type=section&id=Other%20Income%2C%20Net) [Interest Income, Net](index=29&type=section&id=Interest%20Income%2C%20Net) - Interest income is generated from investments in money market funds and U.S. treasuries, net of fees[135](index=135&type=chunk) [Results of Operations](index=29&type=section&id=Results%20of%20Operations) [Comparison of the Three Months Ended June 30, 2025 and 2024](index=29&type=section&id=Comparison%20of%20the%20Three%20Months%20Ended%20June%2030%2C%202025%20and%202024) | Metric (in thousands) | June 30, 2025 | June 30, 2024 | Change | | :-------------------- | :------------ | :------------ | :----- | | Research and development expenses | $(38,278) | $(39,273) | $995 | | General and administrative expenses | $(8,468) | $(5,895) | $(2,573) | | Total other income, net | $3,472 | $4,154 | $(682) | | Net loss | $(43,274) | $(41,014) | $(2,260) | - R&D expenses decreased by **$1.0 million**, primarily due to a **$4.5 million** decrease in preclinical and clinical costs from the conclusion of the lorundrostat pivotal program, partially offset by increased compensation and clinical supply costs[137](index=137&type=chunk) - G&A expenses increased by **$2.6 million**, mainly due to **$1.9 million** higher compensation expenses from headcount additions, salary increases, and stock-based compensation, along with increased professional fees[138](index=138&type=chunk) - Total other income, net, decreased by **$0.7 million** due to lower average cash balances invested, resulting in decreased interest earned[139](index=139&type=chunk)[140](index=140&type=chunk) [Comparison of the Six Months Ended June 30, 2025 and 2024](index=30&type=section&id=Comparison%20of%20the%20Six%20Months%20Ended%20June%2030%2C%202025%20and%202024) | Metric (in thousands) | June 30, 2025 | June 30, 2024 | Change | | :-------------------- | :------------ | :------------ | :----- | | Research and development expenses | $(76,157) | $(70,027) | $(6,130) | | General and administrative expenses | $(15,036) | $(10,503) | $(4,533) | | Total other income, net | $5,708 | $8,008 | $(2,300) | | Net loss | $(85,485) | $(72,522) | $(12,963) | - R&D expenses increased by **$6.1 million**, primarily driven by a **$5.6 million** increase in compensation expenses due to headcount additions, salary increases, and stock-based compensation[142](index=142&type=chunk) - G&A expenses increased by **$4.5 million**, mainly due to a **$3.1 million** increase in compensation expenses and a **$1.3 million** increase in professional fees[143](index=143&type=chunk) - Total other income, net, decreased by **$2.3 million**, primarily due to lower average cash balances invested[144](index=144&type=chunk) [Liquidity and Capital Resources](index=30&type=section&id=Liquidity%20and%20Capital%20Resources) - The Company has incurred net losses and negative cash flows from operations since inception, with an accumulated deficit of **$388.0 million** as of June 30, 2025[145](index=145&type=chunk) - Since inception, the Company has raised approximately **$717.4 million** in gross proceeds from various equity and warrant sales[145](index=145&type=chunk) - As of June 30, 2025, cash, cash equivalents, and investments totaled **$324.9 million**, believed sufficient to fund operations for at least twelve months[145](index=145&type=chunk)[147](index=147&type=chunk) [Funding Requirements](index=31&type=section&id=Funding%20Requirements) - Future capital requirements depend on factors such as clinical trial timing and costs, regulatory approvals, manufacturing, intellectual property protection, and commercialization efforts[148](index=148&type=chunk) - The Company expects to finance future cash needs through equity offerings, debt financings, or strategic collaborations, facing risks of dilution, restrictive covenants, and adverse market conditions[149](index=149&type=chunk) - Failure to raise additional funds on favorable terms could force delays, reductions, or termination of product development and commercialization efforts[149](index=149&type=chunk) [Cash Flows](index=33&type=section&id=Cash%20Flows) [Comparison of the Six Months Ended June 30, 2025 and 2024](index=33&type=section&id=Comparison%20of%20the%20Six%20Months%20Ended%20June%2030%2C%202025%20and%202024) | Cash Flow Activity (in thousands) | Six Months Ended June 30, 2025 | Six Months Ended June 30, 2024 | Change | | :-------------------------------- | :----------------------------- | :----------------------------- | :----- | | Net cash used in operating activities | $(75,656) | $(49,285) | $(26,371) | | Net cash used in investing activities | $(135,757) | $(48,216) | $(87,541) | | Net cash provided by financing activities | $199,110 | $116,053 | $83,057 | [Operating Activities](index=33&type=section&id=Operating%20Activities) - Net cash used in operating activities increased by **$26.4 million** to **$75.7 million** for the six months ended June 30, 2025, primarily due to increased cash used for lorundrostat development, clinical trial expenses, personnel costs, and professional fees[152](index=152&type=chunk) [Investing Activities](index=33&type=section&id=Investing%20Activities) - Net cash used in investing activities increased by **$87.5 million** to **$135.8 million** for the six months ended June 30, 2025, mainly driven by the timing and volume of marketable securities purchases and maturities[153](index=153&type=chunk) [Financing Activities](index=33&type=section&id=Financing%20Activities) - Net cash provided by financing activities increased by **$83.1 million** to **$199.1 million** for the six months ended June 30, 2025[154](index=154&type=chunk) - This increase was primarily due to **$188.9 million** from a public offering and **$8.9 million** from ATM Share sales in 2025, compared to **$116.1 million** from a private placement in 2024[154](index=154&type=chunk) [Contractual Obligations and Commitments](index=33&type=section&id=Contractual%20Obligations%20and%20Commitments) - The Company has contingent milestone and royalty payment obligations under the Mitsubishi License, currently unestimable in timing or likelihood[155](index=155&type=chunk) - Other contracts for research, manufacturing, and professional services are generally cancelable after a notice period[156](index=156&type=chunk) [Critical Accounting Estimates](index=34&type=section&id=Critical%20Accounting%20Estimates) - No material changes occurred in critical accounting estimates during the six months ended June 30, 2025, as disclosed in the Annual Report on Form 10-K for 2024[158](index=158&type=chunk) [JOBS Act and Smaller Reporting Company Status](index=34&type=section&id=JOBS%20Act%20and%20Smaller%20Reporting%20Company%20Status) - The Company, an EGC, elected the extended transition period for new accounting standards, potentially making its financial statements non-comparable to other public companies[159](index=159&type=chunk) - The Company remains an EGC until the earliest of five years post-IPO, **$1.235 billion** in annual gross revenue, becoming a large accelerated filer, or issuing over **$1.0 billion** in non-convertible debt[160](index=160&type=chunk) - The Company also qualifies as a smaller reporting company, allowing for scaled disclosures[161](index=161&type=chunk) [Recently Issued Accounting Pronouncements](index=35&type=section&id=Recently%20Issued%20Accounting%20Pronouncements) - The Company reviewed recently issued accounting pronouncements and determined no material impact on its condensed financial statements or operations, beyond prior disclosures[162](index=162&type=chunk) [Item 3. Quantitative and Qualitative Disclosures About Market Risk](index=35&type=section&id=Item%203.%20Quantitative%20and%20Qualitative%20Disclosures%20About%20Market%20Risk) This section discusses the Company's exposure to market risks, including interest rate, foreign currency, and inflation, and their potential financial impact [Interest Rate Risk](index=35&type=section&id=Interest%20Rate%20Risk) - The Company is exposed to interest rate risk from its investment portfolio, primarily money market funds and U.S. treasury securities[163](index=163&type=chunk) - An immediate hypothetical **10%** change in interest rates is not expected to materially affect the Company's results of operations[163](index=163&type=chunk) [Foreign Currency Exchange Risk](index=35&type=section&id=Foreign%20Currency%20Exchange%20Risk) - The Company is exposed to foreign currency exchange risk from contracts with international vendors denominated in foreign currencies[164](index=164&type=chunk) - Foreign currency fluctuations have not been significant to date; a hypothetical **10%** change in exchange rates is not expected to have a material effect[164](index=164&type=chunk) [Effects of Inflation](index=35&type=section&id=Effects%20of%20Inflation) - Inflation primarily affects the Company by increasing labor and research and development contract costs[165](index=165&type=chunk) - While inflation has not had a material impact to date, future effects on clinical trial costs, labor, and operational expenses could adversely affect the business[165](index=165&type=chunk) [Item 4. Controls and Procedures](index=35&type=section&id=Item%204.%20Controls%20and%20Procedures) This section details the Company's disclosure controls and procedures, including management's evaluation and any changes in internal control [Evaluation of Disclosure Controls and Procedures](index=35&type=section&id=Evaluation%20of%20Disclosure%20Controls%20and%20Procedures) - The Company maintains disclosure controls and procedures designed to ensure timely and accurate reporting of information required by SEC rules[166](index=166&type=chunk) - Management acknowledges that controls provide only reasonable, not absolute, assurance, involving judgment in evaluating cost-benefit relationships[166](index=166&type=chunk) [Conclusion Regarding the Effectiveness of Disclosure Controls and Procedures](index=36&type=section&id=Conclusion%20Regarding%20the%20Effectiveness%20of%20Disclosure%20Controls%20and%20Procedures) - As of June 30, 2025, the principal executive and financial officers concluded the Company's disclosure controls and procedures were effective at a reasonable assurance level[167](index=167&type=chunk) [Changes in Internal Control over Financial Reporting](index=36&type=section&id=Changes%20in%20Internal%20Control%20over%20Financial%20Reporting) - Management determined no material changes in internal control over financial reporting during the three months ended June 30, 2025[168](index=168&type=chunk) [Part II - Other Information](index=37&type=section&id=Part%20II%20-%20Other%20Information) [Item 1. Legal Proceedings](index=37&type=section&id=Item%201.%20Legal%20Proceedings) The Company is not currently a party to any material legal proceedings - The Company is not currently a party to any material legal proceedings, though it may become involved in ordinary course litigation[169](index=169&type=chunk) [Item 1A. Risk Factors](index=37&type=section&id=Item%201A.%20Risk%20Factors) This section updates the Company's risk factors, including inflation and trade policy changes, and their potential adverse effects - The inflation risk factor now includes adverse effects of trade policy changes, such as tariffs, potentially increasing procurement costs or necessitating supplier transitions[171](index=171&type=chunk) - Elevated inflation, geopolitical conflicts, and global supply chain disruptions contribute to economic uncertainty, potentially making future financing more difficult, costly, or dilutive[172](index=172&type=chunk)[173](index=173&type=chunk) [Item 2. Unregistered Sales of Equity Securities and Use of Proceeds](index=37&type=section&id=Item%202.%20Unregistered%20Sales%20of%20Equity%20Securities%20and%20Use%20of%20Proceeds) No unregistered sales of equity securities or use of proceeds were reported for the period - No unregistered sales of equity securities and use of proceeds were reported[174](index=174&type=chunk) [Item 3. Defaults Upon Senior Securities](index=38&type=section&id=Item%203.%20Defaults%20Upon%20Senior%20Securities) No defaults upon senior securities are reported - This item is not applicable, indicating no defaults upon senior securities[175](index=175&type=chunk) [Item 4. Mine Safety Disclosures](index=38&type=section&id=Item%204.%20Mine%20Safety%20Disclosures) Mine safety disclosures are not applicable to the Company - This item is not applicable, indicating no mine safety disclosures[176](index=176&type=chunk) [Item 5. Other Information](index=38&type=section&id=Item%205.%20Other%20Information) No directors or officers adopted or terminated Rule 10b5-1 trading arrangements during the three months ended June 30, 2025 - No directors or officers adopted or terminated any Rule 10b5-1 trading arrangements during the three months ended June 30, 2025[177](index=177&type=chunk) [Item 6. Exhibits](index=38&type=section&id=Item%206.%20Exhibits) This section lists exhibits filed with Form 10-Q, including organizational documents, certifications, and XBRL data files | Exhibit Number | Exhibit Description | Incorporated by Reference Form | Date | Number | Filed Herewith | | :------------- | :------------------------------------------------------------------------------------------------------ | :----------------------------- | :------- | :----- | :------------- | | 3.1 | Amended and Restated Certificate of Incorporation | 8-K | 2/14/23 | 3.1 | | | 3.2 | Amended and Restated Bylaws | 8-K | 2/14/23 | 3.2 | | | 31.1 | Certification of Principal Executive Officer pursuant to Rules 13a-14(a) and 15d-14(a) under the Securities Exchange Act of 1934, as adopted pursuant to Section 302 of the Sarbanes-Oxley Act of 2002 | | | | x | | 31.2 | Certification of Principal Financial Officer pursuant to Rules 13a-14(a) and 15d-14(a) under the Securities Exchange Act of 1934, as adopted pursuant to Section 302 of the Sarbanes-Oxley Act of 2002 | | | | x | | 32.1* | Certification of Principal Executive Officer pursuant to 18 U.S.C. Section 1350, as adopted pursuant to Section 906 of the Sarbanes-Oxley Act of 2002 | | | | x | | 32.2* | Certification of Principal Financial Officer pursuant to 18 U.S.C. Section 1350, as adopted pursuant to Section 906 of the Sarbanes-Oxley Act of 2002 | | | | x | | 101.INS | XBRL Instance Document | | | | x | | 101.SCH | XBRL Taxonomy Extension Schema Document | | | | x | | 101.CAL | XBRL Taxonomy Extension Calculation Linkbase Document | | | | x | | 101.DEF | XBRL Taxonomy Extension Definition Linkbase Document | | | | x | | 101.LAB | XBRL Taxonomy Extension Label Linkbase Document | | | | x | | 101.PRE | XBRL Taxonomy Extension Presentation Linkbase Document | | | | x | | 104 | Cover Page Interactive Data File (formatted as Inline XBRL and contained in Exhibit 101) | | | | x | * This certification is deemed not filed for the purpose of Section 18 of the Exchange Act or otherwise subject to the liability of that section, nor shall it be deemed incorporated by reference into any filing under the Securities Act or the Exchange Act. [SIGNATURES](index=39&type=section&id=SIGNATURES) - The report is signed by Jon Congleton, President and Chief Executive Officer, and Adam Levy, Chief Financial Officer and Secretary, on August 12, 2025[183](index=183&type=chunk)