Delving into the Latest Updates on Avenciguat with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

BI 685509, BI-685509, BI685509

Target

sGC

Action

stimulants

Mechanism

sGC stimulants(Soluble guanylate cyclase stimulants)

Therapeutic Areas

Immune System DiseasesInfectious DiseasesCardiovascular Diseases+ [3]

Active Indication

Decompensated cirrhosis of liverScleroderma, SystemicScleroderma, Diffuse+ [5]

Inactive Indication

Diabetic NephropathiesEsophageal and Gastric VaricesHepatic Insufficiency+ [2]

Originator Organization

Boehringer Ingelheim GmbH

Active Organization

Boehringer Ingelheim GmbHBoehringer Ingelheim RCV GmbH & Co. KGBoehringer Ingelheim España SA

+ [2]

Inactive Organization

Boehringer Ingelheim International GmbHAlmac Pharma Services Ltd.

License Organization-

Drug Highest PhasePhase 2

First Approval Date-

RegulationOrphan Drug (United States), Orphan Drug (European Union)

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Structure/Sequence

Molecular FormulaC34H38N4O5

InChIKeyKWNFFNFBUMFTHK-UHFFFAOYSA-N

CAS Registry1579514-06-9

This study is open to people with and without severe liver problems. People can join the study if they are 18 to 80 years of age and have a body mass index (BMI) between 18.5 and 42 kg/m2.
Avenciguat (BI 685509) is a medicine that is being developed to treat high blood pressure in the portal vein (main vessel going to the liver). The purpose of this study is to find out whether having liver problems influences how Avenciguat (BI 685509) is taken up in the body. All participants take Avenciguat (BI 685509) once as a tablet.
Participants are in the study for slightly longer than 1 month. Following the screening period of about 4 weeks, they stay at the study site for 4 nights. Afterwards, there are 2 visits to the study site. The site staff measures the amount of Avenciguat (BI 685509) in the blood. The doctors also regularly check participants' health and take note of any unwanted effects.

Start Date03 May 2024

Sponsor / Collaborator

Boehringer Ingelheim GmbH

NCT06193811

/ CompletedPhase 1

Relative Bioavailability of Two Different Tablet Formulations of BI 685509 and Investigation of the Effects of Food and Esomeprazole on the Pharmacokinetics of BI 685509 Following Oral Administration in Healthy Male and Female Subjects (an Open-label, Randomised, Four-way Crossover Trial)

The main objective of this trial is to investigate:
* the relative bioavailability of Avenciguat (BI 685509) TF2 (Reference, R) vs. Avenciguat (BI 685509) iCF (Test 1, T1) tablets under fasted conditions
* the relative bioavailability of Avenciguat (BI 685509) iCF tablets under fasted (T1) and fed (Test 2, T2) conditions
* the relative bioavailability of Avenciguat (BI 685509) iCF tablets given alone (T1) and together with esomeprazole (Test 3, T3) under fasted conditions

Start Date16 Jan 2024

Sponsor / Collaborator

Boehringer Ingelheim GmbH

NCT06082843

/ TerminatedPhase 2

Randomised, Double-blind, Placebo-controlled and Parallel Group Trial to Investigate the Effects of One Dose (Up-titration to a Fixed Dose Regimen) of Oral BI 685509 on Portal Hypertension After 8 Weeks Treatment in Patients With Clinically Significant Portal Hypertension (CSPH) in Decompensated Cirrhosis After Their First Decompensation Event, Who Are Stabilized CTP 5-7

This study is open to adults with advanced liver cirrhosis caused by hepatitis B, hepatitis C, alcohol-related liver disease, non-alcoholic steatohepatitis or other causes. People can join the study if they have high blood pressure in the portal vein (main vessel going to the liver) and bleeding in the esophagus or fluid accumulation in the belly. The purpose of this study is to find out whether a medicine called avenciguat helps people with this condition.
Participants are put into 2 groups by chance. One group takes avenciguat tablets and the other group takes placebo tablets. Placebo tablets look like avenciguat tablets but do not contain any medicine. Participants take a tablet twice a day for 8 weeks.
Participants are in the study for 2 to 3 months. During this time, they visit the study site regularly. At 2 of the visits, the doctors check the pressure in the liver vein by inserting a catheter (a long thin tube) that gives information about pressure in the portal vein. The change in blood pressure is then compared between the 2 groups to see whether the treatment works. The doctors also regularly check participants' health and take note of any unwanted effects.

Start Date03 Jan 2024

Sponsor / Collaborator

Boehringer Ingelheim GmbH

100 Clinical Results associated with Avenciguat

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100 Translational Medicine associated with Avenciguat

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100 Patents (Medical) associated with Avenciguat

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13

Literatures (Medical) associated with Avenciguat

02 Jan 2026·EXPERT OPINION ON INVESTIGATIONAL DRUGS

Mass balance and absolute bioavailability of avenciguat ( ¹⁴ C) after intravenous or oral administration in healthy male participants

Article

Author: Joseph, David ; Herich, Lena ; Gao, Eric ; Mitra, Pallabi ; Auclair, Adam M. ; Wolfgang, Taylor ; Wong, Diane ; Tiessen, Renger

BACKGROUND:

Avenciguat, a potent nitric oxide-independent activator of soluble guanylyl cyclase, is being evaluated in chronic kidney disease and systemic sclerosis. We assessed avenciguat absolute bioavailability and mass balance.

RESEARCH DESIGN AND METHODS:

Open-label Phase 1 trial in healthy men. Doses: Part A, 3 mg [¹⁴C]-avenciguat single dose (oral solution); Part B, 3 mg unlabeled avenciguat (tablet) then 30 µg [¹⁴C]-avenciguat (intravenous). Primary endpoints: Part A, mass balance and recovery of [¹⁴C] radioactivity in excreta; Part B, absolute bioavailability. Safety and pharmacokinetics were evaluated.

RESULTS:

In Part A (N = 6), geometric mean recovery of [¹⁴C] radioactivity was 90.0% (range 80.6-96.0%). Elimination was mainly via feces (geometric mean 85.3%; range 76.5-91.3%); urine (4.66%; range 4.10-5.31%). In Part B (N = 6), the absolute bioavailability of avenciguat was 83.0%. In pooled plasma, the predominant drug-related component was avenciguat (mean 86.8%); the acyl glucuronide metabolite represented 5.2% of radioactivity. Drug-related adverse events (AEs) occurred in 33.3% (4/12) of participants, mostly mild, with one moderate presyncope event. No AEs leading to discontinuation were reported.

CONCLUSIONS:

Avenciguat was generally well tolerated and was primarily excreted unchanged in feces and minimally excreted in urine. After oral administration, avenciguat has high oral bioavailability.

CLINICAL TRIAL REGISTRATION:

ClinicalTrials.gov (NCT05515328).

01 Aug 2025·RHEUMATOLOGY

Avenciguat: a novel soluble guanylate cyclase activator that affects multiple cell types to inhibit IFN-1 signalling and fibrosis

Article

Author: Tran-Manh, Cuong ; Zhou, Xiang ; Ebenezer, David L ; Kaufman, Julia ; Nabozny, Gerald ; Wohnhaas, Christian T ; Liebel, Christoph ; Delic, Denis ; Distler, Jörg H W ; Wang, Chao-Ting ; Trinh-Minh, Thuong ; Daley, Lee-Anne

Abstract:

Objectives:

The soluble guanylate cyclase (sGC) stimulator riociguat is approved for the treatment of pulmonary arterial hypertension and may have antifibrotic effects. However, in fibrotic tissues, oxidative stress and hypoxia can render sGC insensitive to sGC stimulators. sGC activators overcome this limitation. Here, we characterize the novel sGC activator, avenciguat, in preclinical models of SSc.

Methods:

Human microvascular endothelial cells-dermal (HMVEC-d) cultured in hypoxic conditions and activated human platelet-rich plasma were incubated with varying doses of avenciguat, and the levels of TGF-β2 and human CXC chemokine family ligand 4 (CXCL4) were measured, respectively. Treatment with avenciguat was analysed in mice with bleomycin-induced dermal and pulmonary fibrosis.

Results:

Avenciguat reduced hypoxia-induced synthesis of TGF-β2 by HMVEC-d and inhibited CXCL4 release by platelets. Moreover, avenciguat demonstrated antifibrotic effects on bleomycin-induced dermal and pulmonary fibrosis. RNA sequencing of affected skin uncovered a unique profile distinguishing avenciguat from riociguat. Avenciguat treatment resulted in deeper regulation of IFN-1 signalling and genes associated with immune response vs riociguat treatment.

Conclusion:

In preclinical studies, avenciguat shows the potential to influence vascular, fibrotic and immune-related processes in murine models of SSc. These studies suggest that it may offer therapeutic benefit across multiple aspects of SSc pathophysiology and support the rationale for further investigation in a Phase II clinical trial (VITALISScE™; NCT05559580) of avenciguat in SSc.

01 May 2025·ANNALS OF INTERNAL MEDICINE

Nephrology: What You May Have Missed in 2024

Review

Author: Alkhajah, Hussa ; Sehgal, Ashwini R. ; Alfarsi, Razan ; Collins, Jhonna ; Alfadhel, Abdulla

This article highlights some important nephrology studies published in 2024 that may be relevant for nonnephrologist physicians. Four studies examined progression of chronic kidney disease (CKD), cardiovascular events, and nephrolithiasis with respect to use of semaglutide or sodium-glucose cotransporter-2 inhibitors. Three studies examined treatments to improve specific aspects of CKD management, including mineralocorticoid receptor agonists to address heart failure, avenciguat to address albuminuria, and oral phosphate binders to address fracture risk. One study demonstrated that inorganic nitrate reduced the risk for contrast-induced nephropathy. Finally, a trial of cefepime-taniborbactam showed benefit for treating complicated urinary tract infection.

2

News (Medical) associated with Avenciguat

26 Feb 2026

·www.fiercebiotech.com

Boehringer pens $500M pact with British biotech for oral approach to autoimmune diseases

Carine Boustany, Ph.D., head of immunology and respiratory diseases research at Boehringer Ingelheim, said autoimmune and inflammatory diseases “remain areas where innovation is urgently needed.” \n Boehringer Ingelheim has penned a $500 million deal with a British biotech for a preclinical program the German pharma hopes could offer a fresh oral treatment approach to a variety of autoimmune and inflammatory diseases.In return for the exclusive global license to Sitryx’s small molecule inhibitor program, the Oxford, England-based biotech could receive upfront and milestone payments in excess of $500 million, although the companies didn’t offer a breakdown of the financials. In addition, Sitryx will receive a slice of the royalties should a drug make it to market.Boehringer is banking on the program offering a new oral and precision approach to modulating disease-driving immune cells, the pharma explained in a Feb. 26 release.Autoimmune-focused Sitryx, which has a presence in Boston, launched in 2018 with the backing of GSK and SV Health Investors. Since then, Sitryx had been exploring the role of metabolic pathways in the function of immune cells, with Eli Lilly handing the biotech $50 million in 2020 for the rights to up to four autoimmune drugs. The pharma later took one of these drugs, an itaconate mimetic dubbed SYX-1042, into a phase 1 study before handing the asset back in August 2025 citing “strategic considerations and reprioritization of Lilly’s pain and inflammation portfolio.”The returned SYX-1042 is now the most advanced drug in Sitryx’s portfolio, followed by SYX-5219, a PKM2 modulator in phase 1 development for atopic dermatitis. The biotech’s preclinical pipeline includes a GLS1 inhibitor for allergic asthma and an SIK2 inhibitor for ulcerative colitis. Sitryx CEO Iain Kilty, Ph.D., said today’s deal with Boehringer marks a “major milestone for our company and is a clear validation of the strength of our pipeline and our expertise translating immunometabolic targets into meaningful therapeutic candidates.”“We are proud to out-license this preclinical program to Boehringer Ingelheim whose global capabilities in immunology and drug development will help position this program to deliver meaningful benefits to patients worldwide,” Kilty added.This morning’s agreement with Sityrx continues a busy few months of dealmaking for Boehringer. This year alone has already seen the German drugmaker pen a 1.05 billion euro ($1.26 billion) biobucks deal for Simcere’s preclinical inflammatory bowel disease bispecific antibody as well as a $120 million kidney-focused collaboration with Variant Bio.Meanwhile, the pharma’s existing clinical-stage immunology pipeline includes the likes of the sGC activator avenciguat for systemic sclerosis and a TREM-1 antagonist for ulcerative colitis.Carine Boustany, Ph.D., head of immunology and respiratory diseases research at Boehringer, said autoimmune and inflammatory diseases “remain areas where innovation is urgently needed.” “Sitryx’s small molecule inhibitor program brings forward a promising new mechanism that aligns with our focus on advancing first-in-class approaches,” Boustany added in the release. “Together with Sitryx, we are committed to translating this science into therapies that can meaningfully improve patients’ lives.”

License out/inPhase 1Immunotherapy

05 May 2023

·www.prnewswire.com

Chronic Kidney Disease Competitive Landscape Report 2023: Comprehensive Insights About 75+ Companies and 95+ Drugs

DUBLIN, May 5, 2023 /PRNewswire/ -- The "Chronic Kidney Disease - Competitive landscape, 2023" report has been added to ResearchAndMarkets.com's offering. This report provides comprehensive insights about 75+ companies and 95+ drugs in Chronic Kidney Disease Competitive landscape. It covers the therapeutics assessment by product type, stage, route of administration, and molecule type. It further highlights the inactive pipeline products in this space. In March 2023, POXEL SA, announced the publication of preclinical results in autosomal dominant polycystic kidney disease (ADPKD) for PXL770, a novel, first-in-class direct adenosine monophosphate-activated protein kinase (AMPK) activator. For the first time, POXEL SA showed beneficial effects of a direct and selective AMPK activator in preclinical ADPKD models from three species mouse, human, and dog. These results confirm the potential utility of AMPK activation for this disease and support the development of PXL770 in a Phase 2 clinical program for ADPKD. In February 2023, AstraZeneca announced the successful completion of the acquisition of CinCor Pharma, Inc. The acquisition bolsters AstraZeneca's cardiorenal pipeline by adding baxdrostat (CIN-107), an aldosterone synthase inhibitor (ASI) for blood pressure lowering in treatment-resistant hypertension, to its cardiorenal portfolio. In January 2023, The U.S. Food and Drug Administration (FDA) has accepted a supplemental New Drug Application (sNDA) for Jardiance (empagliflozin) tablets, which is being investigated as a potential treatment to reduce the risk of kidney disease progression and cardiovascular death in adults with chronic kidney disease (CKD), Boehringer Ingelheim and Eli Lilly and Company announced. In November 2022, The Medical Research Council Population Health Research Unit (MRC PHRU) at the University of Oxford, which designed, conducted and analyzed EMPA-KIDNEY in a scientific collaboration with Boehringer Ingelheim and Eli Lilly and Company, announced that EMPA-KIDNEY phase III clinical trial met its primary endpoint by demonstrating a significant kidney and cardiovascular benefit for adults living with chronic kidney disease (CKD). When treated with Jardiance (empagliflozin), the risk of kidney disease progression or cardiovascular death was significantly reduced by 28% vs. placebo (HR; 0.72; 95% CI 0.64 to 0.82; P< 0.0001). In October 2022, Revelation Biosciences Inc. announced positive results in a preclinical model of acute kidney injury (AKI), chronic kidney disease (CKD). Treatment with REVTx-300 significantly reduced renal cortical fibrosis in a dose dependent manner in the medium and high dose groups (21.7% reduction (p < 0.05) and 29.3% (p < 0.05), respectively) and was comparable to a known TGF inhibitor of fibrosis used as a positive control (38.1% reduction (P < 0.05)). In October 2022, French Biopharma Company, Poxel SA announced the U.S. Food and Drug Administration (FDA) has granted orphan drug designation (ODD) to PXL770 for the treatment of patients with autosomal-dominant polycystic kidney disease (ADPKD). PXL770 is a novel, first-in-class direct adenosine monophosphate-activated protein kinase (AMPK) activator - and is also a phase 2 ready ADPKD asset, subject to additional financing. In-depth Commercial Assessment: Chronic Kidney Disease Collaboration Analysis by Companies The Report provides in-depth commercial assessment of drugs that have been included, which comprises collaboration, agreement, licensing and acquisition - deals values trends. The sub-segmentation is described in the report which provide company-company collaboration (licensing/partnering), company academic collaboration and acquisition analysis in tabulated form. Current Treatment Scenario and Emerging Therapies: How many companies are developing Chronic Kidney Disease drugs? How many Chronic Kidney Disease drugs are developed by each company? How many emerging drugs are in mid-stage, and late-stage of development for the treatment of Chronic Kidney Disease? What are the key collaborations (Industry-Industry, Industry-Academia), Mergers and acquisitions, licensing activities related to the Chronic Kidney Disease therapeutics? What are the recent trends, drug types and novel technologies developed to overcome the limitation of existing therapies? What are the clinical studies going on for Chronic Kidney Disease and their status? What are the key designations that have been granted to the emerging and approved drugs? Key Players Boehringer Ingelheim Eli Lilly and Company Reata Pharmaceuticals Novo Nordisk KBP Biosciences AstraZeneca Allena Pharmaceuticals SCOHIA PHARMA DiaMedica Therapeutics CinCor Pharma Galapagos NV Sentien Biotechnologies, Inc. Regeneron Pharmaceuticals UnicoCell Biomed OccuRx Pharmicell Lisata Therapeutics Unicycive Therapeutics Senda Biosciences Sarfez Pharmaceuticals Rege Nephro Orgenesis GNI Group Algomedix Maze Therapeutics Chinook Therapeutics Angion Biomedica Corp Arch Biopartners Scohia Pharma Algernon Pharmaceuticals TICEBA GmbH Key Products Empagliflozin Bardoxolone methyl Ziltivekimab KBP-5074 AZD9977 ALLN-346 BI-685509 SCO-792 DM199 Baxdrostat GLPG2737 SBI-101 REGN5459 ELIXCYTE FT011 Cellgram-CKD CLBS201 UNI-494 Research Program SZ007 Renal progenitor cells MSCKD F351 Research programme: TRPC6 antagonist APOL1 Programme Research and discovery programs: severe chronic kidney disease ROCK2 Inhibitor LSALT peptide SCO-116 Repirinast Polycystic kidney disease (PKD) For more information about this report visit About ResearchAndMarkets.com ResearchAndMarkets.com is the world's leading source for international market research reports and market data. We provide you with the latest data on international and regional markets, key industries, the top companies, new products and the latest trends. Media Contact: Research and Markets Laura Wood, Senior Manager [email protected] For E.S.T Office Hours Call +1-917-300-0470 For U.S./CAN Toll Free Call +1-800-526-8630 For GMT Office Hours Call +353-1-416-8900 U.S. Fax: 646-607-1907 Fax (outside U.S.): +353-1-481-1716 Logo: SOURCE Research and Markets

Clinical ResultAcquisitionPhase 2Phase 3Orphan Drug

100 Deals associated with Avenciguat

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Liver Cirrhosis	Phase 2	Australia	Boehringer Ingelheim Pharma GmbH & Co., KG	27 Feb 2024
Liver Cirrhosis	Phase 2	Australia	Boehringer Ingelheim International GmbH	27 Feb 2024
Decompensated cirrhosis of liver	Phase 2	United States	Boehringer Ingelheim RCV GmbH & Co. KG	16 Feb 2024
Decompensated cirrhosis of liver	Phase 2	United States	Boehringer Ingelheim GmbH	16 Feb 2024
Decompensated cirrhosis of liver	Phase 2	United States	Boehringer Ingelheim España SA	16 Feb 2024
Decompensated cirrhosis of liver	Phase 2	China	Boehringer Ingelheim España SA	16 Feb 2024
Decompensated cirrhosis of liver	Phase 2	China	Boehringer Ingelheim GmbH	16 Feb 2024
Decompensated cirrhosis of liver	Phase 2	China	Boehringer Ingelheim RCV GmbH & Co. KG	16 Feb 2024
Decompensated cirrhosis of liver	Phase 2	Japan	Boehringer Ingelheim GmbH	16 Feb 2024
Decompensated cirrhosis of liver	Phase 2	Japan	Boehringer Ingelheim España SA	16 Feb 2024

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT05515328 (Pubmed \| Expert Opin Investig Drugs)	Phase 1	-	12	Avenciguat 3 mg [14C]-avenciguat single dose (oral solution)	lwgzlbguoj(meubeanjli) = mnvvxmmpzo tkgcjwjkke (argaguvamh ) View more	Positive	13 Jan 2026
				Avenciguat 3 mg unlabeled avenciguat (tablet) then 30 μg [14C]-avenciguat (intravenous)	tvvntdajav(slbhzhxjqb) = wbtwmfkfbg pplotxmmhc (nuxgdoolej )
NCT05161481 (CTgov)	Phase 2	Esophageal and Gastric Varices \| Hypertension, Portal \| Hypertension ... View more	80	Placebo matching Avenciguat (BI 685509) (Placebo)	ieapatvxlf(qsopsjrdpk) = bndekaczeg oubqufeubx (heehhuouby, jnssmnsghq - mlxtaxprzs) View more	-	15 Jun 2025
				Avenciguat (BI 685509) (Avenciguat 2 mg BID)	ieapatvxlf(qsopsjrdpk) = drfcmtvetm oubqufeubx (heehhuouby, xmerxtvslp - qxbhtpfypw) View more
NCT06082843 (CTgov)	Phase 2	Liver Cirrhosis, Alcoholic \| Liver Cirrhosis	22	Placebo (Placebo)	sktuhsjwog = ojprbovfvw xbpeonrpcl (bjzimvwurk, ejzrrixwnf - zdrswgotym) View more	-	12 Jun 2025
				Avenciguat (Avenciguat)	sktuhsjwog = fpvsorjlvg xbpeonrpcl (bjzimvwurk, zlmkbavezs - xepecvwcfn) View more
NCT05282121 (CTgov)	Phase 2	Hepatitis A \| Esophageal and Gastric Varices \| Metabolic Dysfunction Associated Steatohepatitis ... View more	90	Avenciguat (Patients With HBV - Avenciguat)	kcakapwvhv(hgowjeeddb) = wjpjcxidrb opjpgyavae (jxrmarpmem, 6.66) View more	-	29 Apr 2025
				Avenciguat (Patients With HCV - Avenciguat)	kcakapwvhv(hgowjeeddb) = rhajvlmhmk opjpgyavae (jxrmarpmem, 7.09) View more
NCT04736628 (CTgov)	Phase 2	Non-diabetic Chronic Kidney Disease	261	Avenciguat (Avenciguat 1 mg TID)	lzjplikpkq(zumyswgvgk) = puwpckraok quxxlxbucv (fuznitusaq, 0.067) View more	-	04 Sep 2024
				Avenciguat (Avenciguat 2 mg TID)	lzjplikpkq(zumyswgvgk) = udrxizavxg quxxlxbucv (fuznitusaq, 0.068) View more
NCT04750577 (CTgov)	Phase 2	Diabetic Nephropathies	243	BI 685509 (BI 685509 1 mg TID)	txgaytwezl(ijcgzrxech) = qywauzpbug kewvktlkox (ufeiixsmav, 0.074) View more	-	23 Jul 2024
				BI 685509 (BI 685509 3 mg TID)	txgaytwezl(ijcgzrxech) = wnjixjasdv kewvktlkox (ufeiixsmav, 0.076) View more
NCT04750577 \| NCT04736628 (Two Randomized Placebo-Controlled Trials, Pubmed \| J Am Soc Nephrol)	Phase 2	Non-diabetic Chronic Kidney Disease \| Diabetic Nephropathies	500	Avenciguat 1 mg TID	ssdxrcipib(vjddkzrdwo) = cmjdwitkpd bpopoaznak (rfoffknbns, -26.4 to -3.0) View more	Positive	25 May 2024
				Avenciguat 2 mg TID	ssdxrcipib(vjddkzrdwo) = olczwtgzyo bpopoaznak (rfoffknbns, -24.6 to -0.1) View more
BI-685509 (ASN2022)	Phase 2	Diabetic Nephropathies	50	BI-685509 30 mpk/day	vhfsqlfqld(lgnqrhorav) = whvfatxayx hhiigfpuub (mccedxorkw ) View more	Positive	05 Nov 2022
				BI-685509 100 mpk/day	vhfsqlfqld(lgnqrhorav) = hhrkkjtwwc hhiigfpuub (mccedxorkw ) View more