A Multi-Center, Randomized, Placebo-Controlled, Double-Blind, Adaptive Dose-Ranging Study to Assess Safety and Efficacy of Intravenous OCE-205 in Adults Diagnosed With Cirrhosis With Ascites Who Have Developed Hepatorenal Syndrome-Acute Kidney Injury (HRS-AKI)

OCE-205 is being tested to treat participants who have developed Hepatorenal Syndrome-Acute Kidney Injury as a complication of cirrhosis with ascites.
The study aims are to evaluate the safety and efficacy of OCE-205 at various doses.
Participants will receive treatment by intravenous infusion. Participants will continue with this treatment until participants meets primary endpoint or any discontinuation criteria.

Start Date28 Apr 2022

Sponsor / Collaborator

Ocelot Bio, Inc.

100 Clinical Results associated with Invopressin

100 Translational Medicine associated with Invopressin

100 Patents (Medical) associated with Invopressin

Literatures (Medical) associated with Invopressin

01 Sep 2023·Clinical Drug Investigation

OCE-205, A Novel, Selective Vasopressin Receptor Mixed Agonist-Antagonist: Safety, Tolerability, and Pharmacokinetics/Pharmacodynamics from a Phase 1 Study in Healthy Volunteers

Article

Author: Bagger, Yu ; Ravis, William R ; Harris, Geoff ; Bukofzer, Stan

BACKGROUND:

OCE-205, a novel, selective vasopressin V1a receptor mixed agonist/antagonist with no V2 receptor activity, may treat the portal hypertension-related complications of end-stage liver disease with an improved therapeutic profile over currently utilized nonselective full-agonist vasopressin analogs.

OBJECTIVES:

This Phase 1, double-blind, placebo-controlled, within-dose-group randomized trial investigated the safety, tolerability, and pharmacokinetic/pharmacodynamic profiles of OCE-205 in healthy adults.

METHODS:

Subjects received a single intravenous dose of OCE-205 0.1, 0.3, 0.45, 0.6, or 0.9 mg, or placebo infused over 6 h. Safety and tolerability were assessed, and blood samples were obtained for pharmacokinetic analyses. Sixty-four subjects were randomized and treated.

RESULTS:

Area under the concentration-time curve (AUC) and maximum plasma concentrations (C_max) were approximately dose-proportional across doses from 0.1 to 0.9 mg. OCE-205 terminal half-life was ~ 1.5 h. Diastolic, and to a lesser extent systolic, blood pressure increased in all OCE-205 dose groups; pulse rate decreased. Overall changes in mean arterial pressure were similar to changes in diastolic blood pressure. Absolute changes in cardiac output, by echocardiogram, were somewhat dose-dependent, with mean reductions of 3-12% after the 0.9 mg dose, and individual reductions ≤ 20 to 25% across all doses. The most frequent adverse events were abdominal pain, abnormal gastrointestinal sounds, and diarrhea, with no reported cases of mesenteric ischemia. Adverse events were generally mild or moderate in severity.

CONCLUSION:

OCE-205 was safe and well tolerated, with a pharmacodynamic profile achieving submaximal partial agonism consistent with mixed agonism-antagonism of the V1a receptor. OCE-205 shows promise as a treatment for some complications of end-stage liver disease.

01 Sep 2023·Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie

Partial vasopressin 1a receptor agonism reduces portal hypertension and hyperaldosteronism and induces a powerful diuretic and natriuretic effect in rats with cirrhosis and ascites

Article

Author: Ginès, Pere ; Harris, Geoff ; Fernández-Varo, Guillermo ; Cable, Edward ; Jiménez, Wladimiro ; Bukofzer, Stan

The vasopressin system has emerged as a therapeutic focus for lowering portal hypertension and reducing splanchnic vasodilation in patients with refractory ascites. Clinically available vasopressin agonists are limited by preferential selectivity for V1 receptors that also have steep concentration-response curves with potential risks of excess vasoconstriction and/or complete antidiuretic effects. OCE-205 is a novel, selective, partial V1a receptor agonist with mixed agonist/antagonist activity and no V2 receptor activation at therapeutic doses. We carried out two studies assessing the in vivo effects of OCE-205 in different rat models of cirrhosis and ascites. In a carbon tetrachloride rat cirrhosis model, OCE-205 administration produced a marked reduction in portal hypertension and hyperaldosteronism, along with robust diuretic and natriuretic effects. These effects were accompanied by marked decreases in ascites volume, with three of five animals experiencing total mobilization of ascites. There was no evidence of fluid overload or sodium or water retention, confirming OCE-205's lack of V2 receptor activity. In a second, corroborative study using a bile duct ligation rat model of ascites, OCE-205 produced significant decreases in ascites volume and body weight and a significant increase in urine volume versus vehicle. Urine sodium excretion increased significantly after the first administration of OCE-205 relative to vehicle; however, repeat administration over 5 days did not lead to hyponatremia. Thus, in separate in vivo models, the mixed agonist/antagonist OCE-205 demonstrated relevant and expected endpoint findings consistent with its known mechanism of action and in vitro pharmacology without apparent unwanted effects or nonspecific toxicities.

01 Jan 2023·Current research in pharmacology and drug discovery

OCE-205 in rats and non-human primates: Pharmacokinetic and pharmacodynamic analysis

Article

Author: Bukofzer, Stan ; Harris, Geoff ; Cable, Edward E

Institutional protocol number:

Procedures were approved by the Ferring Research Institute (FRI) Institutional Animal Care and Use Committee (IACUC) on November 27, 2006 under protocol FRI 06-011, and by the Sinclair Research Center IACUC under protocol S11177.

News (Medical) associated with Invopressin

20 Dec 2023

·www.businesswire.com

Ocelot Bio Receives FDA Orphan Drug Designation for OCE-205 for the Treatment of Ascites

REDWOOD CITY, Calif.--( BUSINESS WIRE )--Ocelot Bio, Inc., a clinical-stage biopharmaceutical company focused on the development of innovative therapeutics to treat complications of end-stage liver disease (ESLD), today announced that the U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation to its lead candidate OCE-205 for the treatment of ascites due to all etiologies except cancer. “The FDA granting Orphan Drug Designation for OCE-205 in ascites is validation of the tremendous need for improved therapies offering novel approaches for patients and supports our clinical focus on this important indication,” said Lise Kjems, M.D., Ph.D., chief medical officer at Ocelot Bio. “This milestone serves as a catalyst as we work with patients, healthcare professionals and health authorities to pave a brighter path forward for these patients who have limited treatment options. We are well positioned to further advance our clinical development program for OCE-205 and look forward to progressing this program in ascites.” Ascites is the abnormal accumulation of fluid within the peritoneal cavity of the abdomen and the hallmark of progression into the decompensated phase of cirrhosis. Data suggest that approximately 400,000 people live with ascites, with 60,000 refractory to standard-of-care treatment and who require much more aggressive treatment approaches. 1,2 Current treatments for ascites are limited, are often invasive procedures and may come with significant risks and burden for patients, underscoring the critical need for novel advancements that improve outcomes for those suffering from this devastating condition. Ocelot Bio plans to initiate clinical studies of OCE-205 in refractory ascites in 2024. The FDA grants Orphan Drug Designation to drugs and biologics intended for the treatment, diagnosis or prevention of rare diseases or conditions affecting fewer than 200,000 people in the United States. Orphan Drug Designation provides Ocelot Bio certain benefits, including financial incentives to support clinical development and the potential for up to seven years of market exclusivity for the drug for the designated orphan indication in the U.S. if the drug is ultimately approved for its designated indication. This is the second Orphan Drug Designation for OCE-205, which previously received the designation in hepatorenal syndrome. About OCE-205 Ocelot Bio’s lead asset, OCE-205, is a therapeutic peptide with a differentiated mechanism of action that has potential for improving outcomes for patients with complications of end-stage liver disease (ESLD). OCE-205’s innovation emanates from its design as a mixed agonist-antagonist peptide selective for the vasopressin 1a (V1a) receptor with no vasopressin 2 (v2) receptor activity at drug concentrations well above those used in treating ESLD. By virtue of its mixed V1a agonist/antagonist activity, OCE-205 treatment is designed to relieve portal hypertension while offering a capped maximal efficacy that avoids excessive vasoconstriction seen with full agonists, that leads to ischemic injury and potentially other serious adverse events such as respiratory failure. By eliminating V2 activity, OCE-205 treatment is designed to avoid fluid retention and overload. A Phase 2 clinical trial has completed enrollment to evaluate OCE-205 for the treatment of hepatorenal syndrome with acute kidney injury (HRS-AKI) ( NCT05309200 ), and clinical studies for ascites are expected to initiate in 2024. The U.S. Food and Drug Administration (FDA) granted Orphan Drug Designation for OCE-205 in the treatment of hepatorenal syndrome in 2022 and in ascites in 2023. About Ocelot Bio Ocelot Bio is a clinical-stage biopharmaceutical company focused on the development of innovative therapeutics designed to significantly improve outcomes for patients with liver disease. The company’s lead clinical candidate, OCE-205, is a peptide therapeutic with a mechanism of action designed to selectively target complications of portal hypertension, such as hepatorenal syndrome with acute kidney injury (HRS-AKI) and ascites, serious and life-threatening consequences of end-stage liver disease (ESLD). The company was founded by leading experts in peptide therapeutic development and is backed by a strong syndicate of investors including Venrock, RA Capital Management and Vivo Capital. For more information, visit www.ocelotbio.com . References 1 Siqueira F, et al. Gastroenterol Hepatol (N Y) . 2009;5(9):647-656. 2 Orman, et al. JAMA Netw Open . 2019;2;2(10):e1913673.

Orphan DrugPhase 2

25 Apr 2023

·www.fiercehealthcare.com

Chutes & Ladders—Seema Verma, former CMS head, joins Oracle; Children's Hospital Los Angeles names new CIO

None Welcome to this week's Chutes & Ladders, our roundup of hirings, firings and retirings throughout the industry. Please submit the good news—or the bad—from your shop, and we will feature it here at the end of each week. Oracle Former Centers for Medicare & Medicaid Services (CMS) Administrator Seema Verma is joining software giant Oracle. Verma will be senior vice president and general manager of Oracle Life Sciences, the company’s clinical trials business. She will lead the Oracle Life Sciences and Oracle Cerner Enviza lines of business. Oracle extended its reach into the healthcare industry with its $28 billion acquisition of medical records software company Cerner last year. As administrator for the federal CMS during the Trump administration, Verma was responsible for 6,000 employees and 100,000 contractors as well as coverage for 145 million beneficiaries. During her tenure at CMS, Verma pushed forward several major interoperability initiatives as well as policies to advance value-based care and price transparency, while reducing drug prices and regulations through the Patients over Paperwork Initiative. Most recently, she served as a senior adviser to private equity firms Cressy & Co. and TPG. “Seema has a proven track record of success in both public and private sector healthcare,” said Mike Sicilia, executive vice president of Oracle Global Industries. “Because of this, she has a unique understanding of how to bring together those on the cutting edge of innovation and those in charge of regulation to help our customers make critical medical breakthroughs and bring new therapies to market.” Children's Hospital Los Angeles Children's Hospital Los Angeles tapped Conrad Band as its permanent senior vice president and chief information officer. Band has held the CIO role in an interim capacity since May 2021. He will continue providing vision, strategy and direction for information systems and technology throughout the CHLA enterprise. He oversees all CHLA Information Services (IS) teams—IT Operations; Infrastructure; Technology Training and Adoption; Information Security and Applications—as well as key vendors that provide technology solutions for CHLA. Band joined CHLA in 2017 as chief information security officer. He took on the interim CIO role in the middle of the COVID-19 pandemic, and under his leadership the IS team has been able to support the organization in innovative and collaborative new ways, including remote work and expanded telehealth capabilities, the hospital said. Lehigh Valley Orthopedic Institute Thomas Graham, M.D., a renowned orthopedic hand surgeon, healthcare executive, author, inventor and entrepreneur, has been named the first physician in chief of Lehigh Valley Orthopedic Institute. Graham has served as the hand surgery consultant, team physician or medical director for the PGA Tour and numerous professional teams in the NFL, MLB, NHL and NBA. He has cared for more than 2,000 professional athletes. As physician in chief, Graham will lead the development of new programs, services and technology within the Orthopedic Institute while continuing to provide patient care. Lehigh Valley Orthopedic Institute comprises more than 200 providers at 100 practice and rehabilitation locations. Orthopedic Institute surgeons perform more than 17,000 procedures annually, three times as many joint replacements and twice as many sports medicine procedures than others in the regions LVHN serves. Virta Digital diabetes company Virta tapped Siobhan Nolan Mangini to join its board of directors. Mangini brings more than two decades of healthcare experience to her role. Currently, she serves as president and chief financial officer at NGM Biopharmaceuticals, a biotech company focused on developing immuno-oncology treatments. Before that, Mangini was the president and CFO of healthcare navigation company Castlight Health and held healthcare roles at Bain Consulting and the Kaiser Family Foundation. With a breadth of experience scaling both private and public healthcare companies, Mangini will be an invaluable asset to guide Virta through its next phase of growth and in its quest to reach its eventual goal of reversing diabetes in 100 million people, the company said. > Swiss biotech company Engimmune Therapeutics AG announced Lars Nieba, Ph.D., as its new chief executive officer. Dr. Søren Mouritsen, co-founder and previous CEO, steps down in a planned transition. > CVS Health named a veteran insurance executive to lead its Aetna unit. Brian Kane will join CVS as executive vice president and president of Aetna effective Sept. 1. > Craig Johnson was named executive vice president and COO of Chicago-based Northwestern Medicine. He has served as Northwestern University's executive vice president since 2018. > Tabula Rasa HealthCare appointed Brian Adams as president and CEO. Adams was serving as TRHC's interim CEO since September 2022 and previously served as the company's co-president and chief financial officer. The company also announced that Richard W. Rew II has joined as chief legal officer and corporate secretary. > AccessHope tapped Joy Kincaid to serve as the company's chief product officer. > Lisa Joldersma is joining Avalere Health as its new strategic adviser. Joldersma will support the policy practice by bringing deep expertise in Medicare, commercial and employer-based insurance, and state policy issues, according to the company. > Biotech company Abivax SA appointed Michael Ferguson as new chief commercial officer. > Former FDA research leader Nicholas Kozauer, M.D., has joined Biohaven's executive leadership team as senior vice president for clinical development and regulatory strategy. > LexisNexis Risk Solutions, a provider of data and analytics, hired Adam Mariano as the new president and general manager of its healthcare division. > Digital health lawyer Andrea Linna joins Wilson Sonsini Goodrich & Rosati's regulatory department as a partner. She will be a part of the firm’s digital health industry group and its FDA regulatory, healthcare and consumer products practice. > Nobi, a provider of innovative age-tech solutions, added Sarah Thomas, one of the U.S.’ leading age-tech experts, to its board of directors. > Lise Kjems, M.D., Ph.D., has jumped over to clinical-stage biopharmaceutical company Ocelot Bio to serve as its new chief medical officer. Kjems will oversee the clinical development efforts for Ocelot Bio’s lead candidate, OCE-205, for the treatment of hepatorenal syndrome with acute kidney injury and ascites.

Executive Change

18 Apr 2023

·www.biospace.com

Ocelot Bio Appoints Lise Kjems, M.D., Ph.D., as Chief Medical Officer

Dr. Kjems brings over 20 years of experience leading impactful clinical development teams and programs Dr. Kjems succeeds Stan Bukofzer, M.D., following his retirement; Dr. Bukofzer will continue to serve as Strategic Advisor to Company SAN DIEGO--(BUSINESS WIRE)-- Ocelot Bio, Inc., a clinical-stage biopharmaceutical company focused on the development of innovative therapeutics to treat complications of end-stage liver disease (ESLD), today announced that Lise Kjems, M.D., Ph.D., has joined the organization as chief medical officer. Dr. Kjems will oversee the clinical development efforts for Ocelot Bio’s lead candidate, OCE-205, for the treatment of hepatorenal syndrome with acute kidney injury (HRS-AKI) and ascites. Dr. Kjems succeeds founding chief scientific & medical officer, Stan Bukofzer, M.D., who will provide continued guidance to Ocelot Bio as a Strategic Advisor. This press release features multimedia. View the full release here: Ocelot Bio Appoints Lise Kjems, M.D., Ph.D., as Chief Medical Officer (Photo: Business Wire) “Dr. Bukofzer has played a pivotal role in the advancement of OCE-205 for the treatment of ESLD and in advancing OCE-205 toward the current Phase 2 clinical studies, and I am grateful for his many contributions to the company,” said Katherine Vega Stultz, chief executive officer at Ocelot Bio. “I am thrilled to welcome Dr. Kjems to the role of chief medical officer and am confident that her depth of experience leading successful clinical programs will add incredible value to the Ocelot Bio team. She will serve an important role at Ocelot Bio, and I look forward to what we will accomplish together in the coming years.” Dr. Kjems holds more than 20 years of experience in R&D across a breadth of therapeutic categories, including liver disease, endocrinology, rare disease, autoimmune, gastrointestinal and infectious disease. She has a proven track record in leading high performing teams and delivering on complex programs, with deep experience in bringing products from first-in-human studies through to approval. Prior to joining Ocelot Bio, Dr. Kjems was the chief medical officer at Cyclo Therapeutics where she led its global program evaluating Trappsol® Cyclo™ in Alzheimer’s and rare disease. Earlier in her career, Dr. Kjems was essential in bringing Albireo Pharma’s drug Bylvay® through its Phase 3 program in progressive familial intrahepatic cholestasis (PFIC) to FDA and EMA approvals, as well as launching pivotal Phase 3 trials for Bylvay in biliary atresia and Alagille syndrome. She has also held various positions of increasing responsibility at Aldeyra Therapeutics, Intarcia Therapeutics, Ionis Pharmaceuticals, Johnson & Johnson and Novartis. Dr. Kjems received her M.D. and her Ph.D. in physiology from the University of Copenhagen Medical Faculty Denmark. She was an invited guest research fellow at the University of Southern California, Keck School of Medicine, and an industrial research fellow at Novo Nordisk A/S Bagsvaerd Denmark & University of Copenhagen. “I am excited by the unique opportunity at Ocelot Bio to redefine the treatment paradigm in end-stage liver disease and the potential to make a meaningful impact on patients in need of new therapeutic options,” said Dr. Kjems. “The scientific foundation and the progress made thus far at Ocelot Bio to address a profound unmet medical need in growing patient populations is tremendous, and the company is well underway to characterize the potential for OCE-205 as a differentiated therapeutic with a strong efficacy, safety and tolerability profile. I am proud to join this team and help drive our mission forward.” About Ocelot Bio Ocelot Bio is a clinical-stage biopharmaceutical company focused on the development of innovative therapeutics designed to significantly improve outcomes for patients with liver disease. The company’s lead clinical candidate, OCE-205, is a peptide therapeutic with a mechanism of action designed to selectively target complications of portal hypertension, such as hepatorenal syndrome with acute kidney injury (HRS-AKI), a serious and life-threatening consequence of end-stage liver disease (ESLD). The company was founded by leading experts in peptide therapeutic development and is backed by a strong syndicate of investors including Venrock, RA Capital Management and Vivo Capital. For more information, visit .

Executive ChangePhase 3Phase 2

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Indication	Highest Phase	Country/Location	Organization	Date
Acute Kidney Injury	Phase 2	United States	Ocelot Bio, Inc.	28 Apr 2022
Acute Kidney Injury	Phase 2	Canada	Ocelot Bio, Inc.	28 Apr 2022
Ascites	Phase 2	United States	Ocelot Bio, Inc.	28 Apr 2022
Ascites	Phase 2	Canada	Ocelot Bio, Inc.	28 Apr 2022
Fibrosis	Phase 2	United States	Ocelot Bio, Inc.	28 Apr 2022
Fibrosis	Phase 2	Canada	Ocelot Bio, Inc.	28 Apr 2022
Hepatorenal Syndrome	Phase 2	United States	Ocelot Bio, Inc.	28 Apr 2022
Hepatorenal Syndrome	Phase 2	Canada	Ocelot Bio, Inc.	28 Apr 2022
End Stage Liver Disease	Phase 1	-	Ocelot Bio, Inc.	-

Clinical Result

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


Literature Manual	Phase 1	End Stage Liver Disease	64	OCE-205	oixswhjawl(wfmjsgtzju) = The most frequent adverse events were abdominal pain, abnormal gastrointestinal sounds, and diarrhea, with no reported cases of mesenteric ischemia. Adverse events were generally mild or moderate in severity. gxydaclnsh (zlrlsuonxs )	Positive	06 Nov 2022
				Placebo

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