KBP BioSciences PTE. Ltd.

Bagsværd, Denmark and Singapore, 16 October 2023 – Novo Nordisk A/S and KBP Biosciences PTE., Ltd. today announced that Novo Nordisk has agreed to acquire ocedurenone for uncontrolled hypertension with potential application in cardiovascular and kidney disease from KBP Biosciences for up to 1.3 billion US dollars. Ocedurenone is an orally administered, small molecule, non-steroidal mineralocorticoid receptor antagonist (nsMRA) that is currently being examined in the phase 3 trial CLARION-CKD in patients with uncontrolled hypertension and advanced chronic kidney disease (CKD). Uncontrolled hypertension is when a person’s blood pressure remains high despite taking two or more blood pressure-lowering treatments. “Hypertension is a leading risk factor for cardiovascular events, heart failure, chronic kidney disease and premature death,” said Martin Holst Lange, executive vice president and head of Development at Novo Nordisk. “With its expected benefit-risk profile, ocedurenone has best-in-class potential in treating uncontrolled hypertension and could help address a major unmet medical need in people living with cardiovascular disease and chronic kidney disease.” “We are delighted to pass the ocedurenone torch to Novo Nordisk, a global leader in management of chronic diseases. We believe this transition could unlock the full potential of ocedurenone and benefit more patients with cardiovascular and kidney disease worldwide,” said Dr. Zhenhua Huang, founder and chairman of KBP Biosciences. “The transition is an exciting inflection point in the discovery, research and development work on ocedurenone carried out by KBP, a young player still establishing itself in the global pharmaceutical industry,” added Dr. Fred Yang, chief development officer of KBP Biosciences. To date, ocedurenone has been investigated in nine clinical trials including the BLOCK-CKD Phase 2b trial. The BLOCK-CKD trial met its primary endpoint with ocedurenone demonstrating a clinically meaningful and statistically significant improvement in systolic blood pressure (SBP) from baseline to day 84 in patients with stage 3b/4 CKD and uncontrolled hypertension. There were no reports of severe hyperkalemia or acute kidney injury with ocedurenone in the trial1. The CLARION-CKD phase 3 trial has been initiated in the US, Europe and Asia with the first patient dosed at the end of 2021 and will continue as planned with a total of more than 600 patients expected to be randomised by more than 150 sites. Novo Nordisk expects to initiate phase 3 trials in additional cardiovascular and kidney disease indications in the coming years, aiming to maximise the full potential of ocedurenone. “We look forward to adding ocedurenone to our pipeline as it will complement our current development programmes in cardiovascular disease and chronic kidney disease,” said Camilla Sylvest, executive vice president, Commercial Strategy & Corporate Affairs at Novo Nordisk. “This deal is closely aligned with our strategic focus on expanding from our core in diabetes into other serious chronic diseases, including through novel drug modalities, to help many more patients living with unmet medical needs.” The closing of the acquisition is subject to receipt of applicable regulatory approvals and other customary conditions and is expected to happen before the end of 2023. The transaction will not impact Novo Nordisk’s previously communicated operating profit outlook for 2023 or the ongoing share buy-back programme. Novo Nordisk will fund the acquisition from financial reserves. KBP Biosciences was represented by Goodwin Procter LLP and Novo Nordisk was represented by Covington & Burling LLP in this transaction. About hypertensionHypertension, also referred to as high blood pressure, is when a person’s blood pressure, the force of blood flowing through the blood vessels, is consistently too high. An estimated 1.28 billion adults aged 30–79 years worldwide have hypertension, two-thirds living in low- and middle-income countries. An estimated 46% of adults with hypertension are unaware that they have the condition and less than half of adults (42%) with hypertension are diagnosed and treated. Approximately 1 in 5 adults (21%) with hypertension have it under control2. There is a significant unmet need in the treatment of hypertension, with a strong association with the risk of cardiorenal events3 4. Despite advances in diagnosis and treatment over the last decades, hypertension was the leading cause of premature death (almost 10 million) in 2015 and has increased by 40% since 19905. About ocedurenoneOcedurenone is a third-generation, non-steroidal, mineralocorticoid receptor antagonist (MRA) with a unique pharmacokinetic (PK) profile characterised by a long half-life and high mineralocorticoid receptor (MR) affinity. Certain MRAs have shown benefits in people with hypertension or heart failure, as well as cardiorenal benefits in patients with chronic kidney disease (CKD) and type 2 diabetes6. Patients with cardiovascular disease, CKD or diabetes are at greater risk for hyperkalemia (elevated potassium in the blood), an electrolyte abnormality that can cause muscle weakness, paralysis, cardiac arrhythmias, and sudden cardiac death. Renin-angiotensin-aldosterone system (RAAS) inhibitors, a group of drugs that includes MRAs, are known to further increase the risk of hyperkalemia. Based on clinical studies conducted to date, ocedurenone has the potential to have favorable efficacy (blood pressure reductions) and tolerability (lower risk of hyperkalemia)1. About CLARION-CKDCLARION-CKD is a multicenter, double-blind, placebo-controlled, randomised phase 3 study of ocedurenone for uncontrolled hypertension in patients with advanced chronic kidney disease (CKD). CLARION-CKD follows the same inclusion criteria as the phase 2b BLOCK-CKD study which achieved its primary endpoint with clinical and statistical significance. For the CLARION-CKD trial, a total of more than 600 patients will be randomised by more than 150 sites. The CLARION-CKD study has been initiated in the United States, Europe, Asia and the first patient was dosed at the end of 2021. About KBP BiosciencesKBP Biosciences is a global, clinical-stage biotechnology company, headquartered in Singapore, focused on discovering, developing, and commercializing innovative small-molecule therapeutics for the treatment of serious cardiorenal and infectious diseases with large unmet medical needs. KBP Biosciences’ pipeline includes four novel drug candidates, two currently in clinical development covering multiple indications. CLARION-CKD, the global Phase 3 clinical trial of Ocedurenone (KBP-5074), is being conducted in patients with advanced CKD and uncontrolled hypertension. For more information about KBP Biosciences, please visit the company website at https://www.kbpbiosciences.com/ About Novo NordiskNovo Nordisk is a leading global healthcare company, founded in 1923 and headquartered in Denmark. Our purpose is to drive change to defeat serious chronic diseases, built upon our heritage in diabetes. We do so by pioneering scientific breakthroughs, expanding access to our medicines, and working to prevent and ultimately cure disease. Novo Nordisk employs about 59,000 people in 80 countries and markets its products in around 170 countries. For more information, visit novonordisk.com, Facebook, X, LinkedIn and YouTube.Contacts for further information Novo Nordisk Media: Ambre James-Brown+45 3079 9289abmo@novonordisk.comElizabeth DeLuca (US)+1 609 580 9868edel@novonordisk.comNovo Nordisk investors: Daniel Muusmann Bohsen+45 3075 2175 dabo@novonordisk.comJacob Martin Wiborg Rode+45 3075 5956jrde@novonordisk.comDavid Heiberg Landsted +45 3077 6915 dhel@novonordisk.comMark Joseph Root (US) +1 848 213 3219mjhr@novonordisk.comSina Meyer +45 3075 6656 azey@novonordisk.comFrederik Taylor Pitter +45 3075 8259 fptr@novonordisk.comKBP Biosciences Media: Richard McGregorrichard.mcgregor@kbpbiosciences.com KBP Biosciences Investors: Julie Zhujulie.zhu@kbpbiosciences.com 1 Bakris G, et al. Hypertension. 2021 Jul;78(1):74-81. Effect of KBP-5074 on Blood Pressure in Advanced Chronic Kidney Disease: Results of the BLOCK-CKD Study - PubMed (nih.gov) 2 World Health Organization (WHO), Global report on hypertension: the race against a silent killer, 2023. Global report on hypertension: the race against a silent killer (who.int) 3 Williams B, et al. J Hypertens. 2018;36(10):1953-2041. 2018 ESC/ESH Guidelines for the management of arterial hypertension: The Task Force for the management of arterial hypertension of the European Society of Cardiology and the European Society of Hypertension: The Task Force for the management of arterial hypertension of the European Society of Cardiology and the European Society of Hypertension - PubMed (nih.gov) 4 Cheung AK, et al. KDIGO. 2021;99(3S):S1-S87. KDIGO 2021 Clinical Practice Guideline for the Management of Blood Pressure in Chronic Kidney Disease - PubMed (nih.gov) 5 Forouzanfar MH, et al. JAMA. 2017;317(2):165-82. Global Burden of Hypertension and Systolic Blood Pressure of at Least 110 to 115 mm Hg, 1990-2015 - PubMed (nih.gov) 6 Kintscher U, et al. Br J Pharmacol. 2022 Jul;179(13):3220-3234. Novel non-steroidal mineralocorticoid receptor antagonists in cardiorenal disease - PubMed (nih.gov) Attachment PR231016_KBP

PRINCETON, N.J., April 17, 2023 /PRNewswire/ -- EMJ Nephrology interviewed two World-renowned experts in nephrology and cardiology, George Bakris and Faiez Zannad, regarding the challenges of treating uncontrolled hypertension (uHTN) in patients with advanced chronic kidney disease (CKD), a large unmet need for safe, effective therapies, and the potential of one therapy, Ocedurenone, to address this need. Original article: EMJ-8.1-2023-1.pdf (emg-health.com) Large Unmet Need Patients with advanced CKD have a high burden of disease, compounded by serious comorbidities, most commonly hypertension. Controlling hypertension is vital in these patients to reduce the associated risks of morbidity and mortality, as well as reducing cardiorenal risk, but treatment options are limited due to safety concerns with the use of existing agents. Current Options Bakris:"The PATHWAY-2 trial showed that in people with resistant hypertension without advanced CKD, spironolactone produced a greater reduction in blood pressure than a β-blocker and an α-blocker. However, it presents safety risks to patients when administered." "Then there is eplerenone, given twice a day, while safe, has a much weaker effect on blood pressure reduction than spironolactone. That's all we've got, so that's what people use." Dr Bakris also mentioned two existing nonsteroidal MRAs, esaxerenone which is "approved exclusively in Japan, for which there are no placebo-controlled comparisons", and Finerenone which "reduces blood pressure (placebo subtracted) variously from 3 mmHg (ARTS-DN, FIGARO-DKD, and FIDELIO-DKD studies) to approximately 8 mmHg (subset analysis from ARTS-DN study, eGFR of approximately 68, though office blood pressure from the same study showed around 3 mmHg reduction)". Future Option - Ocedurenone Bakris:"Now, Ocedurenone, a non-steroidal MRA, shows clear promise in patients whose standard of care includes two, three, or more drugs. Ocedurenone is the only drug that has consistently steadied resistant hypertension in people with advanced CKD." In the first dedicated study of patients with uncontrolled hypertension and advanced CKD (BLOCK-CKD), Ocedurenone demonstrated efficacy in lowering blood pressure, together with a favorable safety profile. The experts were optimistic that it could provide a much-needed treatment option for these patients, with the added potential for reduction in the risk of cardiorenal outcomes. "This study showed that Ocedurenone reduces SBP by 11 mmHg (placebo-subtracted), a reduction that could lead to potential approval. No other agent to date has steadied blood pressure as well in this group of patients. And the point is that these are the patients who need the most help." Zannad reinforced the importance of the hyperkalemia data for the clinical safety of Ocedurenone:"With Ocedurenone, we may for the first time have an MRA that is both safe and efficacious." Bakris added:"A Phase 3 study (CLARION-CKD) of Ocedurenone in a similar patient population is ongoing. I remain optimistic that the signal seen in the BLOCK-CKD study will be seen in this larger study." "I remain excited about Ocedurenone. Its tolerability and efficacy in lowering blood pressure in a very high-risk group will have a significant impact on morbidity." "Mineralocorticoid receptors are so ubiquitous which may allow for indications beyond CKD and cardiovascular conditions. This is likely just the beginning for Ocedurenone." About Ocedurenone (KBP-5074) KBP Biosciences is a global, clinical-stage biotechnology company, headquartered in Princeton, NJ, focused on discovering, developing, and commercializing innovative small-molecule therapeutics for the treatment of serious cardiorenal and infectious diseases with large unmet medical needs. Ocedurenone (KBP-5074) is a non-steroidal MRA discovered and developed by KBP Biosciences. At present, the Phase 3 clinical trial of the first indication for Ocedurenone, advanced CKD and uncontrolled hypertension, is underway. About KBP Biosciences, please visit . SOURCE KBP Biosciences

Hepatic Impairment and Drug-Drug Interaction Study Results Presented PRINCETON, N.J., Jan. 6, 2023 /PRNewswire/ -- KBP Biosciences PTE. Ltd. ("KBP Biosciences" or the "Company"), a clinical-stage biotechnology company dedicated to research, development, and commercialization of innovative medicines for the global market, today announced that an overview of Ocedurenone (KBP-5074) as a potential new treatment option addressing the unmet medical need of patients with uncontrolled and resistant hypertension and advanced CKD was presented by Pablo Pergola MD, PhD. Results of the hepatic impairment study and drug-drug Interaction study were presented as posters at ASN Kidney Week, November 4, 2022. Pablo Pergola MD, PhD, Renal Associates PA, San Antonio, TX, presented an overview of Ocedurenone (KBP-5074). The title of Dr. Pergola's oral presentation was "Nonsteroidal Mineralocorticoid Receptor Blocker (KBP-5074) for Hypertension in Stage 4 CKD." Uncontrolled and resistant hypertension is a major contributor to the excess morbidity and mortality in patients with advanced kidney disease and presents an unmet medical need for new therapies. Dr. Pergola presented the BLOCK CKD Phase 2b trial (NCT03574363) efficacy and safety data for Ocedurenone. He provided a review of Ocedurenone properties that lead to clinically significant BP reduction and reduced risk of hyperkalemia in patients with resistant hypertension and advanced CKD. The ongoing Phase 3 study: CLARION CKD – Efficacy and Safety of KBP-5074 in Uncontrolled Hypertension with Moderate to Severe CKD (NCT04968184) was also presented. Dr. Pergola concluded that "Ocedurenone demonstrates potential as a new treatment option for high-risk patients who suffer from advanced chronic kidney disease and uncontrolled or resistant hypertension." Dr. George Bakris MD, Director of the American Heart Association's Comprehensive Hypertension Center at the University of Chicago Medical Center and session moderator, was asked about the mechanism for BP lowering without significant hyperkalemia. "This is not like spironolactone. Ocedurenone is a non-steroidal MRA and is clearly different. It has different binding properties to the mineralocorticoid receptor with cofactors and gene activation, as well as other physiologic factors that lead to less hyperkalemia." KBP also presented the Hepatic Impairment study and Drug-Drug Interaction study of Ocedurenone (KBP-5074), as posters, at the ASN Kidney Week Conference. The titles of the poster presentations are "Pharmacokinetics of the Novel Nonsteroidal Mineralocorticoid Receptor Antagonist KBP-5074 in Individuals with Moderate Hepatic Impairment" and "Pharmacokinetics and Drug-Drug Interaction of KBP-5074 in Healthy Subjects". In the hepatic impairment study (E-poster link 1), small decreases of area under the plasma concentration-time curve (AUC) and maximum plasma concentration (Cmax) upon systemic exposure to Ocedurenone (KBP-5074) in subjects with moderate hepatic impairment demonstrate low hepatic extraction and a dose adjustment does not appear to be warranted in patients with moderate hepatic impairment. Ocedurenone (KBP-5074) was safe and well tolerated in moderate hepatic impaired subjects. In the drug-drug interaction study (E-poster link 2), Ocedurenone (KBP-5074) was well tolerated when administered as a single 0.5-mg dose alone or in combination with itraconazole or rifampin. The study indicates that a strong Cytochrome P450 3A4 (CYP3A) inhibitor (itraconazole) has a weak effect on Ocedurenone pharmacokinetic properties, with less than 2-fold change in Cmax and area under the curve time zero to time of last measurable concentration (AUClast); whereas a strong CYP3A inducer (rifampin) has a strong effect on the pharmacokinetic properties of Ocedurenone, with about 5-fold decrease in AUC and terminal half-life (T1/2). "The data indicate that there may not be a need for dose adjustment in patients with moderate hepatic impairment and that ocedurenone is safe for use in this population. Co-administration with CYP3A4 inhibitors, commonly used in the target population, also appears to be safe," said James McCabe, MD, Deputy Chief Medical Officer. "Data from these studies add to the growing body of evidence supporting the use of Ocedurenone in clinical medicine," said Julia Yang MD, Chief Operations Officer of KBP, "and provide a compelling rationale for the use of Ocedurenone (KBP-5074) for the treatment of patients with CKD." In addition, KBP Biosciences presented results of a subgroup analysis of the Block-CKD Phase 2b clinical trial of Ocedurenone (KBP-5074) as a poster at the American Heart Association Scientific Sessions in Chicago November 5-7, 2022 (E-poster link 3). "The consistency of SBP reduction and safety data in more severe CKD patients with diabetes is highly informative. The analysis supports the robustness of data supporting the use of Ocedurenone regardless of CKD stage or diabetic status," said Bertram Pitt MD, University of Michigan. "The data provide further justification for the use of Ocedurenone for the treatment of patients with advanced CKD and uncontrolled/resistant hypertension," said Fred Yang PhD, Chief Development Officer of KBP. About KBP Biosciences KBP Biosciences is a global, clinical-stage biotechnology company, headquartered in Princeton, NJ, focused on discovering, developing, and commercializing innovative small-molecule therapeutics for the treatment of serious cardiorenal and infectious diseases with large unmet needs. KBP Biosciences' pipeline includes four novel drug candidates, two currently in clinical development covering multiple indications. CLARION-CKD, the Phase 3 clinical trial of Ocedurenone (KBP-5074), addressing the first indication of advanced CKD and uncontrolled hypertension, is being conducted globally. About Ocedurenone (KBP-5074) Ocedurenone (KBP-5074) is a non-steroidal MRA discovered and developed by KBP Biosciences. Ocedurenone (KBP-5074) selectively binds to recombinant human MRs with much higher affinity than to recombinant human glucocorticoid, progesterone, and androgen receptors which can produce antihypertensive, renal and cardioprotective effects. At present, the Phase 3 clinical trial of the first indication for Ocedurenone (KBP-5074), advanced CKD and uncontrolled hypertension, is underway. Other indications of Ocedurenone are planned, including CV risk reduction, CKD progression, heart failure, etc. Ocedurenone (KBP-5074) has been investigated in nine clinical studies including the BLOCK-CKD Phase 2b study. Ocedurenone (KBP-5074) is expected to provide a new treatment option addressing the unmet medical needs of patients with advanced CKD and uncontrolled hypertension. Block-CKD was a randomized, double-blind, placebo-controlled, multi-center, Phase 2b study to assess the efficacy, safety, and PK of KBP-5074 0.25 mg QD and KBP-5074 0.5 mg QD versus placebo in subjects with moderate to severe CKD and uncontrolled hypertension and demonstrated significant blood pressure lowering with minimum risk of hyperkalemia. The subgroup analysis was conducted to evaluate safety (eGFR change and serum potassium levels) and efficacy (SBP reduction) of Ocedurenone in patients across different CKD stages, and with or w/o diabetes. Similar small dose-dependent increases in serum potassium were observed in nearly all subpopulations. Consistent and clinically meaningful SBP reduction at Day 84 was observed in the subgroups analyzed. These conclusions are being confirmed in a larger ongoing Phase 3 trial ("Clarion-CKD"). E-poster link 1: Pharmacokinetics of the Novel Nonsteroidal Mineralocorticoid Receptor Antagonist Ocedurenone (KBP-5074) in Individuals with Moderate Hepatic Impairment: (final)%20.pdf E-poster link 2: Pharmacokinetics and Drug-Drug Interaction of Ocedurenone (KBP-5074) in Healthy Subjects: E-poster link 3: Effect of Ocedurenone (KBP-5074) in Patients with Uncontrolled Hypertension and Stage 3b/4 Chronic Kidney Disease - Subgroup Analysis of a Phase 2b Clinical Trial: For more information about KBP Biosciences, please visit the company website at SOURCE KBP Biosciences