An In-Depth Analysis of HRS-1780: A Novel Non-Steroidal Mineralocorticoid Receptor Antagonist for Chronic Kidney Disease

Executive Summary

HRS-1780 is an orally administered, investigational small molecule drug being developed for the treatment of chronic kidney disease (CKD). It is classified as a selective, non-steroidal mineralocorticoid receptor antagonist (MRA), a therapeutic class validated by the clinical and commercial success of finerenone. The development of HRS-1780 is primarily led by Jiangsu Hengrui Pharmaceuticals, with Shandong Suncadia Medicine Co., Ltd. also listed as a key sponsor in clinical trial registries. The drug’s mechanism of action involves the direct blockade of the mineralocorticoid receptor (MR), thereby inhibiting the downstream pathological effects of aldosterone, such as inflammation and fibrosis, which are known drivers of cardiorenal disease progression.

Early-phase clinical development has yielded a highly promising profile for HRS-1780. Pharmacokinetic (PK) studies in both healthy volunteers and the target patient population with renal impairment have demonstrated rapid absorption and elimination, with a short half-life of approximately 2-2.5 hours. Critically, the drug's exposure is not significantly affected by mild or moderate renal impairment, suggesting that a consistent dosing regimen may be possible across a broad spectrum of CKD patients without the need for complex adjustments based on kidney function. This represents a significant potential advantage in clinical practice.

The safety and tolerability data from Phase 1 trials are equally encouraging. HRS-1780 has been well-tolerated, with all adverse events reported as mild. Most notably, in a single-dose study involving patients with impaired renal function—a population highly susceptible to MRA-induced hyperkalemia—no clinically significant changes in serum potassium were observed. Furthermore, a thorough cardiac safety assessment revealed no meaningful prolongation of the QTcF interval. While this early safety signal is favorable, it requires confirmation in larger, longer-duration studies.

The clinical development strategy for HRS-1780 appears sophisticated and commercially astute. Recognizing the evolution of the standard of care in CKD, which now includes SGLT2 inhibitors, the ongoing Phase 2 trial is designed as a combination study, evaluating HRS-1780 on top of the SGLT2 inhibitor henagliflozin. This "add-on" approach is clinically relevant and positions HRS-1780 to address the residual cardiorenal risk that persists despite current optimal therapies.

In conclusion, HRS-1780 has emerged as a promising follow-on compound in the non-steroidal MRA class. Its favorable pharmacokinetic profile in renally impaired patients and its encouraging early safety data, particularly regarding hyperkalemia, represent its core potential advantages. The primary challenge will be to demonstrate a clear and clinically meaningful benefit over the established market leader, finerenone. The upcoming results from the Phase 2 combination study will be a critical catalyst, providing the first efficacy and longer-term safety data and setting the stage for a potential pivotal Phase 3 program.

HRS-1780: Profile of an Investigational Cardiorenal Therapeutic

Drug Identity and Classification

HRS-1780 is an investigational, orally bioavailable small molecule drug currently in clinical development.[1] Its formal chemical classification is a selective, non-steroidal mineralocorticoid receptor antagonist (MRA).[2] This classification places it in a modern therapeutic class designed to overcome the limitations of older, steroidal MRAs. The compound is also referred to by the synonyms HRS 1780 and HRS1780 in various research and database entries.[1]

The core therapeutic hypothesis for HRS-1780 is centered on its ability to precisely target and block the mineralocorticoid receptor, a key mediator in the pathophysiology of cardiorenal diseases. Its development is focused on addressing unmet needs in urogenital, endocrine, and metabolic diseases, with the primary active indications being Chronic Kidney Disease (CKD) and Type 2 Diabetes Mellitus (T2DM).[1]

Developer and Corporate Sponsorship

The development and clinical investigation of HRS-1780 are being driven by prominent entities within the Chinese pharmaceutical industry. The most frequently cited organization is Jiangsu Hengrui Pharmaceuticals Co., Ltd. (also referred to as Jiangsu Hengrui Pharma or Hengrui), a major, innovation-focused pharmaceutical company based in China.[5] The direct involvement of Jiangsu Hengrui is substantiated by multiple data points: the company is explicitly named as the sponsor in acknowledgments of published clinical studies, and several of its employees are listed as authors on the corresponding scientific papers.[2] This indicates that the core scientific and financial impetus for the HRS-1780 program originates from within Jiangsu Hengrui.

Concurrently, official clinical trial registration documents, such as those filed with ClinicalTrials.gov, identify Shandong Suncadia Medicine Co., Ltd. as the originator organization and the formal sponsor for key clinical trials, including the pivotal Phase 1 study in renal impairment (NCT06039254) and the ongoing Phase 2 efficacy study (NCT06221059).[1]

The dual attribution of sponsorship and development roles between Jiangsu Hengrui and Shandong Suncadia introduces a layer of complexity to the corporate structure behind HRS-1780. The available documentation does not explicitly define the relationship between these two entities. This could represent a variety of corporate arrangements, such as a parent-subsidiary relationship where Suncadia operates as a specialized division of Hengrui, a strategic joint venture, or a formal licensing agreement wherein Suncadia holds specific rights for the development or commercialization of the asset.

For external stakeholders, such as potential pharmaceutical partners, investors, or licensing bodies, this ambiguity is a non-trivial matter. A clear understanding of the intellectual property ownership, territorial commercialization rights, and the ultimate decision-making authority for the HRS-1780 program is fundamental to any form of due diligence or strategic negotiation. Clarifying this corporate structure would be a necessary step for any party considering engagement with the program, as it directly impacts the assessment of commercial potential, risk, and the long-term strategic direction of this promising therapeutic candidate.

Scientific Rationale and Mechanism of Action in Cardiorenal Disease

The Unmet Need in Chronic Kidney Disease (CKD)

Chronic Kidney Disease is a progressive and debilitating condition defined by a gradual loss of kidney function over time.[2] Its clinical manifestations include proteinuria (excess protein in the urine), hematuria, edema, and hypertension, contributing to a significant global health burden.[2] The pathophysiology of CKD is intimately linked to the overactivation of the renin-angiotensin-aldosterone system (RAAS), a critical hormonal cascade that regulates blood pressure and fluid and electrolyte balance.[4] For decades, the cornerstone of CKD management has been the inhibition of this system using angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs), which are considered primary therapeutic options, especially for patients with significant proteinuria.[2]

Despite the benefits of RAAS inhibition, a substantial residual risk of CKD progression and associated cardiovascular events remains. This is partly because conventional RAAS inhibitors do not fully block the downstream effects of aldosterone, a key hormone in the RAAS cascade. Aldosterone binds to and activates the mineralocorticoid receptor (MR), a nuclear hormone receptor expressed in various tissues, including the kidneys, heart, and blood vessels.[4]

The Role of the Mineralocorticoid Receptor (MR)

In the kidney's distal nephron, MR activation by aldosterone leads to the reabsorption of sodium and the excretion of potassium, thereby regulating blood pressure and fluid volume.[4] However, pathological overactivation of the MR, a common feature in CKD and T2DM, triggers deleterious non-epithelial effects. This sustained MR activation promotes pro-inflammatory and pro-fibrotic gene expression, leading to tissue damage, inflammation, and fibrosis in both the kidneys and the heart.[9] This process is a fundamental driver of the progression from early-stage kidney damage to end-stage renal disease and contributes significantly to the high incidence of cardiovascular morbidity and mortality in CKD patients.

Recognizing this, medical guidelines recommend the use of mineralocorticoid receptor antagonists as an add-on therapy for patients with CKD and T2DM to specifically target and mitigate the harmful effects of MR overactivation.[2]

HRS-1780's Mechanism of Action

HRS-1780 is engineered to directly address this pathological pathway. As a selective non-steroidal MRA, its mechanism of action is the competitive antagonism of the mineralocorticoid receptor.[1] It is reported to possess a "greater MR binding affinity," which suggests a high degree of potency at its molecular target.[2] By binding to the MR, HRS-1780 prevents aldosterone from activating the receptor. This blockade is intended to interrupt the cascade of events that leads to inflammation and fibrosis, thereby protecting the kidneys and cardiovascular system from further damage and slowing the progression of the disease.[9]

Comparative Analysis and Strategic Context

The development of HRS-1780 and its class of non-steroidal MRAs was driven by the significant limitations of earlier, steroidal agents like spironolactone and eplerenone. While effective, these first- and second-generation MRAs are underutilized in clinical practice due to a high risk of inducing hyperkalemia (dangerously elevated serum potassium levels), a risk that is particularly pronounced in the core CKD patient population.[2] Furthermore, their non-selective, steroidal structure leads to off-target hormonal side effects, such as gynecomastia (breast enlargement in men).[10]

The benchmark for the non-steroidal MRA class is finerenone (marketed as Kerendia), which has received regulatory approval from the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for treating CKD in patients with T2DM.[12] Finerenone's development was supported by a robust clinical program, including the landmark Phase 3 FIDELIO-DKD and FIGARO-DKD trials, which collectively demonstrated significant reductions in both renal and cardiovascular composite endpoints.[16] These trials successfully validated the non-steroidal MRA mechanism as a safe and effective strategy for addressing residual cardiorenal risk.

The success of finerenone has fundamentally shaped the landscape for any subsequent drug in this class. HRS-1780 is not a first-in-class molecule but rather a "follow-on" compound entering a field where the therapeutic target has been clinically and commercially de-risked. This context establishes a very high bar for its clinical development program. The central question for HRS-1780 is no longer whether this mechanism of action is viable, but rather how this specific molecule offers a tangible improvement over the established, approved market leader. Consequently, every piece of emerging clinical data for HRS-1780, from its pharmacokinetic behavior to its safety profile and eventual efficacy, will be rigorously scrutinized and compared against the known profile of finerenone. To achieve clinical and commercial success, HRS-1780 must demonstrate a clear and meaningful advantage. This could manifest as a superior safety profile (e.g., a significantly lower incidence of hyperkalemia), enhanced efficacy on key renal or cardiovascular endpoints, a more favorable drug-drug interaction profile, or greater ease of use. Without such differentiation, it risks being perceived as a "me-too" product in a competitive market.

Comprehensive Analysis of Clinical Pharmacology

Pharmacokinetic (PK) Profile in Healthy Volunteers (NCT05638126)

The initial characterization of HRS-1780's clinical pharmacology was established in a comprehensive "four-in-one," first-in-human Phase 1 study conducted in healthy male participants.[3] This trial was designed to assess safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and the drug's effect on the cardiac QTc interval.

The study revealed that HRS-1780 possesses a profile of rapid absorption and rapid elimination. In the single ascending dose (SAD) portion of the trial, where participants received single doses ranging from 5 mg to 80 mg, the time to reach maximum plasma concentration () was very short. This finding was confirmed in the multiple ascending dose (MAD) portion, where participants received daily doses of 10 mg, 20 mg, or 40 mg for seven consecutive days. At steady state, the median  was observed to be 0.750 hours, indicating that the drug reaches peak levels in the blood less than an hour after oral administration. The mean elimination half-life () was correspondingly short, ranging from 1.76 to 1.96 hours, suggesting that the drug is cleared from the body quickly and has a low potential for accumulation with once-daily dosing.[3]

The study also investigated the impact of food on the drug's absorption. When HRS-1780 was administered with a high-fat, high-calorie meal, the  was prolonged. However, this change in the rate of absorption did not affect the overall extent of drug exposure, as measured by the area under the concentration-time curve (AUC).[3] This finding is clinically significant as it suggests that HRS-1780 can be administered to patients without regard to meals, offering greater convenience and flexibility in dosing schedules.

Impact of Renal Impairment on Pharmacokinetics (NCT06039254)

Perhaps the most critical early-stage investigation was the Phase 1, open-label, parallel-controlled study designed to evaluate the pharmacokinetics and safety of HRS-1780 specifically in its target patient population: individuals with renal impairment.[2] This study enrolled three parallel cohorts: healthy subjects with normal renal function (glomerular filtration rate of

 mL/min), subjects with mild renal impairment (GFR of 60-89 mL/min), and subjects with moderate renal impairment (GFR of 30-59 mL/min). All participants received a single 20 mg oral dose of HRS-1780.

The results from this study powerfully reinforced the findings from the healthy volunteer trial and provided crucial insights into the drug's behavior in the presence of kidney disease. The rapid absorption and elimination profile was consistent across all groups, with a median  of 0.50–0.52 hours and a mean  of 2.06–2.56 hours.[1] The most important pharmacokinetic finding was the comparability of drug exposure across the different levels of renal function. The total exposure to HRS-1780, as measured by

, was comparable between the mild and moderate renal impairment groups. While exposure in these groups was slightly higher than in the healthy subjects, the difference was not statistically significant.[1]

Further analysis provided a mechanistic basis for this observation. Plasma protein binding of HRS-1780 was found to be similar among the three groups, indicating that the degree of renal function does not alter the fraction of free, pharmacologically active drug in circulation.[2] As expected, the renal clearance of HRS-1780 decreased as the severity of renal impairment worsened. However, the study concluded that the contribution of renal elimination to the drug's overall clearance was "minimal".[1] This implies that the drug is primarily cleared from the body through non-renal pathways, such as hepatic metabolism.

Regarding metabolites, the study found that exposure to a primary metabolite, identified as SX2183-M3, was significantly increased in subjects with moderate renal impairment.[1] However, this finding is considered to have limited clinical relevance, as this metabolite has been determined to be pharmacologically inactive.[2]

The consistent and predictable pharmacokinetic profile of HRS-1780, particularly its apparent independence from renal function, constitutes a major strategic asset for the drug's development. Many medications used in patients with CKD require complex dose adjustments based on their eGFR to avoid drug accumulation and toxicity. The data from trial NCT06039254 strongly support the conclusion that such adjustments may not be necessary for HRS-1780 in patients with mild to moderate CKD.[1] This potential for a "one-dose-fits-most" regimen would significantly simplify the prescribing process for clinicians, reduce the risk of dosing errors, and enhance the drug's overall user-friendliness. This simplicity could become a key differentiating factor and a powerful driver of physician adoption, should these findings be confirmed in later-stage, chronic-dosing trials.

Pharmacodynamic (PD) Effects and Target Engagement

The first-in-human study also provided clear evidence of pharmacodynamic activity, confirming that HRS-1780 successfully engages its intended molecular target. In healthy men receiving multiple daily doses of 40 mg, a discernible trend toward a decrease in systolic blood pressure was observed when compared to the placebo group.[3]

More definitively, treatment with HRS-1780 resulted in a compensatory increase in plasma levels of both aldosterone and norepinephrine relative to placebo.[3] This is a well-established pharmacodynamic marker for effective MR blockade. By antagonizing the receptor, the drug interrupts the negative feedback loop within the RAAS, leading the body to increase production of upstream hormones. This finding serves as robust in-vivo proof that HRS-1780 is achieving its intended biological effect at the receptor level.

Clinical Safety and Tolerability Profile

Overall Assessment

Across the initial Phase 1 clinical studies, which included both healthy volunteers and subjects with varying degrees of renal impairment, HRS-1780 has consistently demonstrated a favorable safety and tolerability profile.[2] The data gathered to date have not revealed any significant safety concerns that would impede further clinical development.

Adverse Events in Healthy Volunteers (NCT05638126)

In the first-in-human study, HRS-1780 was found to be well-tolerated. Participants received single oral doses ranging from 5 mg to 80 mg and multiple daily doses up to 40 mg for seven days.[3] Throughout this extensive dose range, all reported adverse events (AEs) were classified as mild in severity, and no dose-limiting toxicities were identified.[3]

Adverse Events in Renal Impairment (NCT06039254)

The safety findings from the study in renally impaired subjects are particularly noteworthy, as this represents the target patient population. The overall incidence of treatment-emergent adverse events (TEAEs) was found to be comparable across the three study arms: 55.6% in the healthy subject group, 44.4% in the mild impairment group, and 44.4% in the moderate impairment group.[1] This suggests that the presence of underlying kidney disease does not predispose patients to an increased risk of adverse events following a single dose of HRS-1780.

The vast majority of TEAEs were mild. The most frequently reported events were laboratory abnormalities, specifically increased blood uric acid and increased blood triglycerides.[2] One serious adverse event (SAE)—a case of moderate syncope—was reported in a subject in the mild impairment group. However, after review, this event was deemed by the investigators to be possibly unrelated to the study drug and was attributed to the subject's pre-existing medical history.[2] Importantly, no adverse events led to death or necessitated the discontinuation of treatment.[2]

Key Safety Areas of Interest for MRAs

Given the known risks associated with the MRA drug class, specific safety parameters were closely monitored.

• Hyperkalemia: The risk of hyperkalemia is the primary safety concern and the most common reason for the underutilization of older MRAs in clinical practice. The results for HRS-1780 in this regard are highly encouraging. In the study involving renally impaired subjects, no clinically significant abnormalities in serum potassium levels were observed at any point post-dose.[2] The absence of a hyperkalemia signal, even in a population with compromised kidney function that is inherently at higher risk, is the most significant safety finding for the drug to date.
• Cardiac Safety: The first-in-human study incorporated a thorough evaluation of the drug's potential to affect cardiac repolarization, a standard component of modern drug development. The analysis of the QT interval, corrected for heart rate using Fridericia's formula (QTcF), showed no cause for concern. The upper bounds of the two-sided 90% confidence interval for the placebo-adjusted change-from-baseline QTcF were well below the 10-millisecond threshold of regulatory concern at all doses tested.[3] This leads to the strong conclusion that HRS-1780 does not cause clinically meaningful QTcF prolongation.

While this early safety profile is exceptionally promising, particularly the lack of a hyperkalemia signal, it is essential to interpret these findings with appropriate caution. The data are derived from small-scale, short-duration studies involving a single dose in the renal impairment trial. The true risk profile of HRS-1780, especially concerning hyperkalemia, will only be fully elucidated through chronic dosing in larger patient populations, such as in the ongoing Phase 2 study and future Phase 3 trials. In these later-stage studies, patients will be receiving HRS-1780 for extended periods, often in combination with other medications that can also affect potassium levels (such as ACEIs and ARBs). The safety data from these forthcoming trials, especially the incidence and severity of hyperkalemia, will be the most critical determinant of the drug's ultimate clinical utility and potential for differentiation.

The HRS-1780 Clinical Development Program

Strategic Overview

The clinical development program for HRS-1780 is progressing through a logical and strategically sound sequence of trials. The program began by establishing foundational safety, tolerability, and pharmacokinetic parameters in healthy individuals. It then advanced to a crucial study confirming these properties in the target population of patients with renal impairment. The program now includes planned studies to address regulatory requirements for drug-drug interactions (DDI) and has moved into mid-stage, Phase 2 testing to gather the first data on efficacy and safety in a more realistic clinical setting. This progression reflects a well-reasoned approach to de-risking the asset and building a comprehensive data package.

Table 1: Summary of the HRS-1780 Clinical Development Program

The following table consolidates the key details of the known clinical trials for HRS-1780, providing a clear, at-a-glance overview of the program's scope, status, and strategic direction.

Trial ID	Phase	Title / Purpose	Status	Key Interventions
NCT05638126	Phase 1	A four-in-one first-in-human study to assess safety, tolerability, PK, PD, and concentration-QTc relationship in healthy men.3	Completed	Single Ascending Doses (5-80 mg); Multiple Ascending Doses (10-40 mg daily for 7 days).3
NCT06039254	Phase 1	A multicenter, open-label study to evaluate the safety and pharmacokinetics of HRS-1780 in healthy subjects and subjects with mild or moderate renal impairment.8	Completed	Single 20 mg oral dose of HRS-1780 administered to three parallel cohorts.2
NCT06221059	Phase 2	A multicenter, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of HRS-1780 tablets and Henagliflozin Proline tablets in patients with Chronic Kidney Disease.1	Active, not recruiting 1	HRS-1780 in combination with Henagliflozin Proline (an SGLT-2 inhibitor) versus placebo.19
NCT06344936	Phase 1	An open-label assessment of the effects of itraconazole (a strong CYP3A4 inhibitor) and rifampicin (a strong CYP3A4 inducer) on the pharmacokinetics of HRS-1780 in healthy subjects.1	Not yet recruiting 1	Co-administration of HRS-1780 with potent modulators of the CYP3A4 metabolic enzyme.20
NCT06495931	Phase 1	A single-center, open-label, fixed-sequence study of the pharmacokinetic effects of HRS-1780 in combination with Henagliflozin, Metformin, and HRS-7535 (a GLP-1 agonist) in healthy subjects.1	Not yet recruiting 1	Co-administration of HRS-1780 with a cocktail of standard-of-care medications for T2DM and CKD.1

The design of the overall clinical program, especially the Phase 2 trial and the planned DDI studies, reveals a particularly sophisticated and forward-looking development strategy. The therapeutic landscape for CKD, particularly in patients with T2DM, has undergone a paradigm shift in recent years. The standard of care is no longer limited to RAAS inhibition with ACEIs or ARBs. Sodium-glucose cotransporter-2 (SGLT2) inhibitors, such as dapagliflozin and empagliflozin, have become foundational therapies due to their robustly proven benefits in slowing renal function decline and reducing cardiovascular events.[21] The approved non-steroidal MRA, finerenone, was itself studied and approved as an add-on therapy to this modern standard of care.

The developers of HRS-1780 have clearly recognized this new reality. Instead of pursuing a monotherapy development path, their pivotal Phase 2 trial (NCT06221059) is explicitly designed as a combination study, evaluating the efficacy and safety of HRS-1780 when added to the SGLT2 inhibitor Henagliflozin.[1] This approach directly addresses the most relevant clinical question: can HRS-1780 provide

additional benefit on top of an already optimized, modern therapeutic regimen?

This forward-thinking strategy is further underscored by the planned DDI study, NCT06495931. This trial is designed to assess the pharmacokinetic interactions of HRS-1780 not only with an SGLT2 inhibitor but also with metformin and a GLP-1 receptor agonist (HRS-7535).[1] This demonstrates a clear intent to build a data package that proves HRS-1780 can be safely and effectively co-administered with the full suite of medications that a typical patient with CKD and T2DM is likely to be taking. This "built-for-combination" approach is commercially astute, as it positions HRS-1780 to fit seamlessly into the current treatment paradigm rather than attempting to displace already established and effective therapies. A successful outcome in the Phase 2 combination trial would provide powerful proof-of-concept for this "add-on" positioning and would represent a major value inflection point for the entire program.

Strategic Assessment and Concluding Remarks

Current Position and Potential

HRS-1780 has emerged as a well-characterized, investigational non-steroidal MRA with a compelling profile based on early-stage clinical data. Its development is strategically aligned with a validated therapeutic mechanism for addressing cardiorenal disease. The program's principal assets at this stage are its highly favorable and predictable pharmacokinetic properties, which appear to be largely independent of renal function, and a promising initial safety profile that lacks the key liability of hyperkalemia that has historically limited the use of this drug class.

Key Strengths

• Favorable Pharmacokinetics in the Target Population: The finding that drug exposure is not significantly altered by mild-to-moderate renal impairment is a powerful potential advantage. It suggests the possibility of a simplified, uniform dosing regimen, which would reduce the clinical management burden on physicians and lower the risk of dosing errors for patients.
• Promising Early Safety Profile: The absence of any signal for hyperkalemia in a single-dose study of renally impaired subjects is a critical early de-risking event. Coupled with the lack of any cardiac QTc prolongation, this positions HRS-1780 as a potentially safer alternative to older MRAs.
• Sound Clinical Development Strategy: The decision to pursue a combination therapy approach in the Phase 2 trial, evaluating HRS-1780 as an add-on to the current SGLT2 inhibitor standard of care, is both clinically relevant and commercially savvy. It directly addresses how the drug would be used in real-world practice.

Challenges and Hurdles

• High Competitive Bar: The primary challenge for HRS-1780 is the presence of an established, approved, and effective competitor in finerenone (Kerendia). Finerenone has extensive Phase 3 data demonstrating both renal and cardiovascular outcome benefits and is already being incorporated into treatment guidelines. To gain significant market share, HRS-1780 must demonstrate a clear and clinically meaningful advantage over this incumbent.
• Preliminary Nature of Data: All current conclusions regarding the drug's promising profile are based on small, short-duration Phase 1 studies. The true efficacy and long-term safety, particularly the risk of hyperkalemia with chronic dosing in a larger, more diverse population, remain to be established.
• Development Timelines: As a follow-on compound, HRS-1780 is several years behind the market leader. This gives finerenone a substantial head start to become deeply entrenched in clinical practice, making market penetration more challenging for a new entrant.

Future Outlook and Key Catalysts

The trajectory of the HRS-1780 program will be significantly influenced by several near-term catalysts. The most important of these is the data readout from the Phase 2 clinical trial (NCT06221059). This study will provide the first randomized, placebo-controlled evidence of HRS-1780's efficacy (likely measured by a surrogate endpoint such as the change in urine albumin-to-creatinine ratio) and, critically, its safety and tolerability profile during chronic dosing in combination with an SGLT2 inhibitor.

A positive outcome from this Phase 2 study—demonstrating meaningful efficacy on top of standard of care, coupled with a continued favorable safety profile, especially a low incidence of hyperkalemia—would serve as a major de-risking event and a significant value inflection point. Such a result would validate the combination strategy and provide the necessary support to proceed with a large, expensive, and lengthy pivotal Phase 3 outcomes program. Concurrently, the results from the planned drug-drug interaction studies (NCT06344936 and NCT06495931) will be essential for defining the drug's future label and confirming its ease of use in polypharmacy settings common in this patient population.

In conclusion, HRS-1780 is a promising therapeutic asset within a validated and clinically important drug class. Its development program appears to be well-conceived to address the key scientific and commercial questions necessary for success. While the competitive hurdles posed by an established market leader are significant, the compelling early pharmacokinetic and safety data suggest that HRS-1780 has a genuine potential to become a valuable future therapeutic option for managing the substantial residual cardiorenal risk in patients with chronic kidney disease. Its ultimate success will be contingent upon its ability to translate this early promise into a clear and demonstrable clinical advantage in late-stage trials.

Works cited

1. HRS-1780 - Drug Targets, Indications, Patents - Patsnap Synapse, accessed September 30, 2025, https://synapse.patsnap.com/drug/50e0c54c68984520b2793b282cb07623
2. Pharmacokinetics and Safety of HRS-1780 in Renal Impaired ..., accessed September 30, 2025, https://www.dovepress.com/pharmacokinetics-and-safety-of-hrs-1780-in-renal-impaired-subjects-a-m-peer-reviewed-fulltext-article-DDDT
3. A four-in-one first-in-human study to assess safety, tolerability, pharmacokinetics, pharmacodynamics, and concentration-QTc relationship of HRS-1780, a selective non-steroidal mineralocorticoid receptor antagonist, in healthy men - PubMed, accessed September 30, 2025, https://pubmed.ncbi.nlm.nih.gov/39155700/
4. Pharmacokinetics and Safety of HRS-1780 in Renal Impaired Subjects: A Multicenter, Non-Randomized, Open-Label Study - PMC, accessed September 30, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC12068283/
5. HRS-1780 / Jiangsu Hengrui Pharma - LARVOL DELTA, accessed September 30, 2025, https://delta.larvol.com/Products/?ProductId=25c0d47c-97c8-4a40-b17c-336541d60cd4
6. Pharmacokinetics and Safety of HRS-1780 in Renal Impaired Subjects: A Multicenter, Non-Randomized, Open-Label Study, accessed September 30, 2025, https://www.tandfonline.com/doi/abs/10.2147/DDDT.S500384
7. Pharmacokinetics and Safety of HRS-1780 in Renal Impaired Subjects: A Multicenter, Non-Randomized, Open-Label Study - PubMed, accessed September 30, 2025, https://pubmed.ncbi.nlm.nih.gov/40356678/
8. Study Details | NCT06039254 | Safety and Pharmacokinetics of HRS-1780 in Healthy Subjects and Subjects With Impaired Renal Function | ClinicalTrials.gov, accessed September 30, 2025, https://clinicaltrials.gov/study/NCT06039254
9. A four-in-one first-in-human study to assess safety, tolerability, pharmacokinetics, pharmacodynamics, and concentration-QTc relationship of HRS-1780, a selective non-steroidal mineralocorticoid receptor antagonist, in healthy men - ResearchGate, accessed September 30, 2025, https://www.researchgate.net/publication/383229791_A_four-in-one_first-in-human_study_to_assess_safety_tolerability_pharmacokinetics_pharmacodynamics_and_concentration-QTc_relationship_of_HRS-1780_a_selective_non-steroidal_mineralocorticoid_receptor_a
10. Finerenone: Questions and Answers—The Four Fundamental Arguments on the New-Born Promising Non-Steroidal Mineralocorticoid Receptor Antagonist - MDPI, accessed September 30, 2025, https://www.mdpi.com/2077-0383/12/12/3992
11. Differentiation between emerging non-steroidal and established steroidal mineralocorticoid receptor antagonists: head-to-head comparisons of pharmacological and clinical characteristics, accessed September 30, 2025, https://www.tandfonline.com/doi/full/10.1080/13543784.2021.2002844
12. Kerendia (finerenone) FDA Approval History - Drugs.com, accessed September 30, 2025, https://www.drugs.com/history/kerendia.html
13. Kerendia | European Medicines Agency (EMA) - Europa.eu, accessed September 30, 2025, https://www.ema.europa.eu/en/medicines/human/EPAR/kerendia
14. Bayer scores EU approval for CKD drug Kerendia - FirstWord Pharma, accessed September 30, 2025, https://firstwordpharma.com/story/5502761
15. In which countries is Finerenone approved? - Patsnap Synapse, accessed September 30, 2025, https://synapse.patsnap.com/article/in-which-countries-is-finerenone-approved
16. What clinical trials have been conducted for Finerenone? - Patsnap Synapse, accessed September 30, 2025, https://synapse.patsnap.com/article/what-clinical-trials-have-been-conducted-for-finerenone
17. Finerenone and Cardiovascular Outcomes in Patients With Chronic Kidney Disease and Type 2 Diabetes | Circulation - American Heart Association Journals, accessed September 30, 2025, https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.120.051898
18. Finerenone in Reducing Cardiovascular Mortality and Morbidity in Diabetic Kidney Disease, accessed September 30, 2025, https://www.acc.org/Latest-in-Cardiology/Clinical-Trials/2021/08/25/23/58/FIGARO-DKD
19. Efficacy and Safety of HRS-1780 Tablets and Henagliflozin Proline Tablets in Patients With Chronic Kidney Disease - ClinicalTrials.Veeva, accessed September 30, 2025, https://ctv.veeva.com/study/efficacy-and-safety-of-hrs-1780-tablets-and-henagliflozin-proline-tablets-in-patients-with-chronic-k
20. Drug-drug Interaction Study of HRS-1780 Tablets in - ClinConnect, accessed September 30, 2025, https://clinconnect.io/trials/NCT06344936
21. Dapagliflozin - Wikipedia, accessed September 30, 2025, https://en.wikipedia.org/wiki/Dapagliflozin