About us
Background
LIB Therapeutics was founded in 2015 by Drs. Evan Stein and August Troendle as a private, self-funded company with assets from BMS. The LIB model is totally virtual, highly flexible, and designed to move through all phases of development and regulatory as quickly and smoothly as possible. This has enabled LIB to develop and optimize manufacturing of its lead asset, lerodalcibep (LIB003), complete all preclinical toxicology, phase 1, phase 2 dose selection, a 52-week phase 2b trials, and initiate and enroll 7 large global phase 3 trials in under 6 years.
Our compounds
As a late stage clinical biopharmaceutical company, we are developing novel, best-in-class injectable and oral therapies to inhibit PCSK9 and reduce LDL-C. Our novel platform is a small 11 KDa anti-PCSK9 adnectin, which is derived from the 10th Type 3 domain of human fibronectin (10Fn3). As demonstrated in our preclinical and clinical studies, the high affinity binding of our LIB adnectins to PCSK9 blocks the interaction between PCSK9 and the LDL receptor (LDLR), thereby preventing PCSK9-mediated LDLR degradation and enhancing LDL-C clearance. The anti-PCSK9 adnectin formatted with human serum albumin (HAS) to increase half-life and enhance solubility allows for both longer dosing intervals and smaller injection volumes for SC administration.
Our team
Board of Directors
August Troendle, MD
August Troendle, MD
Dr. Troendle has been the Chief Executive Officer and Chairman of the Board of Directors of Medpace since he founded the Company in July 1992. Before founding Medpace, Dr. Troendle served as Assistant Director, Associate Director and Senior Associate Director from 1987 to 1992 at Sandoz (Novartis), where he was responsible for the clinical development of lipid altering agents.
From 1986 to 1987, Dr. Troendle worked as a Medical Review Officer in the Division of Metabolic and Endocrine Drug Products at the FDA. Dr. Troendle also has extensive experience serving as a director for a diverse group of public and private companies, including as a director of Coherus BioSciences, Inc. from 2012 to February 2018, as a director of Xenon Pharmaceuticals Inc. from 2007 to 2008, as a director of LIB Therapeutics, LLC since 2015, as a director of CinCor Pharma, Inc. from March 2018 to November 2021, and as a director of CinRx Pharma, LLC since 2015.
Dr. Troendle received his Medical Degree from the University of Maryland, School of Medicine and his Master of Business Administration from Boston University.
David A. Cory, RPh, MBA
David A. Cory, RPh, MBA
David Cory is a biopharmaceutical industry leader with 30 years of operational experience in public and private, large pharma and emerging stage biotechnology companies, with an extensive commercial background spanning multiple launches including global blockbuster products and targeted therapeutics for rare diseases, an established track record in the capital markets with over $1B+ raised and multiple companies which have successfully resulted in acquisition.
Mr. Cory was previously President and CEO, Director, and co-founder of Eiger BioPharmaceuticals, a commercial-stage biopharmaceutical company focused on the development of innovative therapies for serious, orphan diseases, and was responsible for negotiating multiple technology and product licenses from Stanford University, Merck, BMS, The Progeria Research Foundation, and Children’s Hospital of Philadelphia to build the pipeline, taking the company public, and obtaining the company’s first FDA and EMA product approvals. Previously, Mr. Cory was President and Chief Operating Officer of Prestwick Pharmaceuticals, an orphan CNS specialty pharmaceutical company, which was acquired by Biovail for $160 million. Earlier, Mr. Cory was a co-founder of CoTherix, an orphan pulmonary arterial hypertension company, which was acquired by Actelion for $425 million. Mr. Cory began his biotech career with the founding team at InterMune, focused on developing orphan products for idiopathic pulmonary fibrosis, where he was Senior Vice President and a key executive in the company IPO, in-licensing 4 products, and building and managing the company’s commercial organization. InterMune was acquired by Roche for $8 billion. Mr. Cory spent over a decade in large pharma in positions of increasing responsibilities in commercial operations at Glaxo, Glaxo Welcome, and Glaxo Smith Kline where he led teams in oncology, critical care, CNS, infectious disease, and respiratory therapeutic areas, and directed 10 newly approved pharmaceutical product launches. Mr. Cory began his pharmaceutical career at The Upjohn Company.
Mr. Cory earned a BS in Pharmacy from the University of Cincinnati, College of Pharmacy, was board certified in Pharmacy in the state of Ohio and holds an MBA from the University of Maryland.
Evan Stein, MD PhD FACC
Evan Stein, MD PhD FACC
Dr Stein received his medical degree and PhD, from the University of Witwatersrand Medical School in Johannesburg, South Africa. In 1972 he started the first Lipid Clinic in South Africa and described the very high gene frequency of FH in the Afrikaner population. After completing his specialist training in Medical Biochemistry at McMaster University Medical Center in Canada he spent 11 years as a full-time faculty member at the University of Cincinnati, Ohio, , achieving the rank of tenured Professor of Pathology and Laboratory Medicine and Associate Professor of Internal Medicine. In 1988, he moved his clinical and laboratory groups and formed the Metabolic and Atherosclerosis Research Center, specializing in clinical trials affecting lipid metabolism and Medical Research Laboratories (MRL) a global central lab for clinical trials. In 2002 MRL was acquired by Pharmaceutical Product Development Inc. In 2006 he rejoined Dr Troendle with whom he had founded Medpace and developed Medpace Reference Laboratories. He remained on the Medpace board until 2012.
Dr. Stein has had a number of appointments to the National Institutes of Health (NIH) since 1986, including the National Cholesterol Education Program. He served on the Data and Safety Advisory Board of the National Heart, Lung, and Blood Institute Program on Genetics in Hypertension from 1999-2003. In 2006 he was appointed to the FDA Clinical Chemistry and Clinical Toxicology Advisory Panel through 2010.
Over the last 35 years Dr. Stein has been an Advisory Board member for a number of pharmaceutical and biotech companies in the lipid area and a member of the board of directors of Xenon Pharmaceuticals, CymaBay and Medpace CRO.
Stephen Ewald
Stephen Ewald
Mr. Stephen P. Ewald, J.D. serves as General Counsel, Corporate Secretary of the Company. Stephen P. Ewald joined Medpace as General Counsel and Corporate Secretary in June 2012.
Prior to joining Medpace, Mr. Ewald served as the Managing Director and Chief Legal Officer of Brevet Capital Management from May 2011 to June 2012. From May 2009 to May 2011, he was a Managing Director and Assistant General Counsel for Cantor Fitzgerald Securities/Cantor Fitzgerald & Co. Mr. Ewald was employed with Bank of America from 1999 to 2009, serving in various roles within the legal department and the Global Markets Group, including Managing Director and Chief Operating Officer of the Principal Capital Group, a proprietary investing group within Bank of America Securities.
Mr. Ewald has served as director for several private companies, including as a director of Symplmed Pharmaceuticals, LLC since 2013, as a director of LIB Therapeutics, LLC since 2016 and as a director of CinRx Pharma, LLC since 2016. Mr. Ewald received his Bachelor of Science in Political Sciences from the University of Cincinnati and his Juris Doctorate from the University of Cincinnati College of Law.
Jesse Geiger
Jesse Geiger
Jesse J. Geiger joined Medpace in October 2007 as Corporate Controller, and he was appointed Chief Financial Officer in March 2011. Mr. Geiger became Chief Operating Officer, Laboratory Operations in November 2014. Mr. Geiger was appointed to the position of President on August 1, 2021. Prior to joining Medpace, Mr. Geiger worked for SENCORP from 2004 to 2007 as the Corporate Controller and Manager of Financial Planning and Analysis.
Prior to SENCORP, Mr. Geiger served as the Director of Capital Markets for Cincinnati Bell from 2002 to 2004. Mr. Geiger started his career in the audit practice at Arthur Andersen LLP. Mr. Geiger has served as a director for several private companies, including as a director of LIB Therapeutics, LLC since 2015 and as a director of CinRx Pharma, LLC since 2015. Mr. Geiger received his Bachelor of Business Administration in Accounting from the University of Cincinnati and is a Certified Public Accountant (Inactive).
Elizabeth Stoner, MD
Elizabeth Stoner, MD
Dr Stoner received her M.D. from the Albert Einstein College of Medicine, her M.S. in Chemistry from SUNY at Stony Brook and her B.S. in Chemistry from Ottawa University, KS and prior to joining the pharmaceutical industry, she was an Assistant Professor of Pediatrics at Cornell University Medical College. At Merck Research Laboratories she rose to Senior Vice President of Global Clinical Development Operations with responsibility for clinical development activities in more than 40 countries. Liz also oversaw the clinical development activities of its Japanese subsidiary and played a leading role in Merck/Schering Plough Joint Venture’s development of Vytorin and Zetia, blockbuster cholesterol lowering drugs.
After leaving Merck Liz joined MPM and has held several leadership roles at MPM portfolio companies including interim CEO of Semma Therapeutics; founder, CMO and Chief Development Officer (CDO) of Rhythm and the CDO of Vascular Pharmaceuticals. She also served in clinical and advisory roles at Clinical Ink, Potenza Therapeutics, Solasia and TriNetX. Liz is a member of the Cures Acceleration Network Review Board of the National Center for Advisory Translations Sciences of the NIH to represent viewpoints of drug development and venture capital professionals regarding the discovery and development of therapeutics, diagnostics and devices.
Dr Stoner joined LIB Therapeutics board in 2016.
Management
David A. Cory, RPh, MBA
David A. Cory, RPh, MBA
David Cory is a biopharmaceutical industry leader with 30 years of operational experience in public and private, large pharma and emerging stage biotechnology companies, with an extensive commercial background spanning multiple launches including global blockbuster products and targeted therapeutics for rare diseases, an established track record in the capital markets with over $1B+ raised and multiple companies which have successfully resulted in acquisition.
Mr. Cory was previously President and CEO, Director, and co-founder of Eiger BioPharmaceuticals, a commercial-stage biopharmaceutical company focused on the development of innovative therapies for serious, orphan diseases, and was responsible for negotiating multiple technology and product licenses from Stanford University, Merck, BMS, The Progeria Research Foundation, and Children’s Hospital of Philadelphia to build the pipeline, taking the company public, and obtaining the company’s first FDA and EMA product approvals. Previously, Mr. Cory was President and Chief Operating Officer of Prestwick Pharmaceuticals, an orphan CNS specialty pharmaceutical company, which was acquired by Biovail for $160 million. Earlier, Mr. Cory was a co-founder of CoTherix, an orphan pulmonary arterial hypertension company, which was acquired by Actelion for $425 million. Mr. Cory began his biotech career with the founding team at InterMune, focused on developing orphan products for idiopathic pulmonary fibrosis, where he was Senior Vice President and a key executive in the company IPO, in-licensing 4 products, and building and managing the company’s commercial organization. InterMune was acquired by Roche for $8 billion. Mr. Cory spent over a decade in large pharma in positions of increasing responsibilities in commercial operations at Glaxo, Glaxo Welcome, and Glaxo Smith Kline where he led teams in oncology, critical care, CNS, infectious disease, and respiratory therapeutic areas, and directed 10 newly approved pharmaceutical product launches. Mr. Cory began his pharmaceutical career at The Upjohn Company.
Mr. Cory earned a BS in Pharmacy from the University of Cincinnati, College of Pharmacy, was board certified in Pharmacy in the state of Ohio and holds an MBA from the University of Maryland.
Evan Stein, MD PhD FACC
Evan Stein, MD PhD FACC
Dr Stein received his medical degree and PhD, from the University of Witwatersrand Medical School in Johannesburg, South Africa. In 1972 he started the first Lipid Clinic in South Africa and described the very high gene frequency of FH in the Afrikaner population. After completing his specialist training in Medical Biochemistry at McMaster University Medical Center in Canada he spent 11 years as a full-time faculty member at the University of Cincinnati, Ohio, , achieving the rank of tenured Professor of Pathology and Laboratory Medicine and Associate Professor of Internal Medicine. In 1988, he moved his clinical and laboratory groups and formed the Metabolic and Atherosclerosis Research Center, specializing in clinical trials affecting lipid metabolism and Medical Research Laboratories (MRL) a global central lab for clinical trials. In 2002 MRL was acquired by Pharmaceutical Product Development Inc. In 2006 he rejoined Dr Troendle with whom he had founded Medpace and developed Medpace Reference Laboratories. He remained on the Medpace board until 2012.
Dr. Stein has had a number of appointments to the National Institutes of Health (NIH) since 1986, including the National Cholesterol Education Program. He served on the Data and Safety Advisory Board of the National Heart, Lung, and Blood Institute Program on Genetics in Hypertension from 1999-2003. In 2006 he was appointed to the FDA Clinical Chemistry and Clinical Toxicology Advisory Panel through 2010.
Over the last 35 years Dr. Stein has been an Advisory Board member for a number of pharmaceutical and biotech companies in the lipid area and a member of the board of directors of Xenon Pharmaceuticals, CymaBay and Medpace CRO.
David Kallend, MB BS
David Kallend, MB BS
Dr Kallend graduated from Kings College Hospital School of Medicine in London, and did further training at the Royal Postgraduate Medical School Hammersmith Hospital, London, as a Research Fellow in the Department of Surgery. In 1995 he joined the pharmaceutical industry as an International Clinical Research Physician on imaging studies for Schering AG in Berlin, predominantly in the area of magnetic resonance contrast media for abdominal and joint imaging.
Following this he joined AstraZeneca, based in the UK, and worked on the development of rosuvastatin from Phase II to Phase IV and the post-approval phase. From 2005 to 2012 he was the Global Clinical Leader and a Group Medical Director for dalcetrapib at Roche and was responsible for Phase II and Phase III clinical development and an advisor for other lipid programs.
In 2012 Dave joined The Medicines Company and was Vice President and Global Medical Director overseeing the siRNA for PCSK9, inclisiran, clinical development program from inception through to NDA filing and approval.
Dr Kallend joined LIB Therapeutics as CMO in 2020.
Shekar Ganesa, PhD
Shekar Ganesa, PhD
Dr. Shekar Ganesa joined LIB Therapeutics in 2020 with 25+ years’ experience and manages the strategic/technical activities related to Process and Analytical development, Manufacturing, Quality, Supply chain, CMC regulatory initiatives at various CDMO’s and CRO’s for Lerodalcibep (LIB003).
Prior to LIB Therapeutics, Shekar has held several leadership roles at MassBiologics, Amgen and Genzyme-Sanofi leading cell line development/banking, upstream, downstream, formulation and analytical development activities for monoclonal antibodies, recombinant complex glycoproteins and gene therapy viral vector-based products leading to several successful INDs filings and BLAs approvals. Shekar continues to be a strong advocate of implementing Quality by Design (QbD) principles to understand, design and control critical product quality attributes while optimizing process performance.
Shekar has published numerous research articles and delivered keynote lectures at several national and international meetings. Dr. Shekar Ganesa received his Ph.D. in Biochemistry from Indiana State University, Terre Haute, IN and subsequently completed a post-doctoral fellowship in Biochemistry at the Worcester Foundation for Experimental Biology.
Tracy Mitchell, PhD
Tracy Mitchell, PhD
Dr. Tracy Mitchell joined LIB Therapeutics in September 2015 to lead non-clinical development of the PCSK9 Adnectins. Her role encompasses preclinical toxicology, bioanalytical PK/PD, immunogenicity, and CMC from drug substance process development through combination product development.
Prior to LIB, Tracy served as Principal Scientist at Bristol Myers Squibb (formerly Adnexus Therapeutics). While at BMS, she co-led the PCSK9 Adnectin discovery team and led the PK enhancement team as well as the Discovery PK group. Before BMS, she was a Research Scientist at Eyetech Pharmaceuticals, focused on novel therapeutics to treat pathological processes in the eye. Prior to Eyetech, Tracy worked at Genetics Institute (currently Pfizer).
Tracy received her PhD in Biomolecular Chemistry from the University of Wisconsin-Madison and her BA in Chemistry from Boston University. She did her post-doctoral work in genetics and angiogenesis at the University of California at San Francisco.
Erin Pirrotta
Erin Pirrotta
Erin Pirrotta joined LIB Therapeutics in 2017 to lead the manufacture of lerodalcibep and optimize the process and analytics for commercial production. Her role and responsibilities encompass managing upstream and downstream process development, analytical development, and drug substance and drug product manufacturing activities at LIB’s CDMOs as well as CMC regulatory filings and compliance.
Erin has 25 years of experience in CMC development and manufacture of biologics and small molecules spanning pre-clinical assessments through commercial approval.
Before joining LIB Therapeutics, Erin led Formulation, Downstream, and Analytical Development groups at Merrimack Pharmaceuticals. Prior to that, she gained experience on a large portfolio of biologics within multiple positions in the Formulation Development group at Wyeth BioPharma, now Pfizer.
Erin received her Master of Science in Biological Sciences from University of Massachusetts Lowell and her BA in Biology with a minor in Chemistry from the University of Pennsylvania.
Kate Caldwell
Kate Caldwell
Kate is a project management and operations professional with 21 years experience, highlighted by rapid advancement and consistent achievement in operational management across diverse industries, ranging from wholesale home and apparel fashions to pharmaceutical R&D at an industry-leading central laboratory.
She is experienced with successful development and oversight of a broad range of clinical trial and central laboratory operations, including study management, regulatory requirements, budgets and finance, inventory, and logistics.
Prior to LIB Therapeutics Kate, served as Director of Client Services at Medpace Reference Laboratories and, prior to that, held multiple laboratory and project management positions at Medical Research Laboratories.
Kate received her BS in Medical Technology from Xavier University and is an ASCP board-certified Medical Technologist.
Kiana Calvin
Kiana Calvin
Kiana joined LIB Therapeutics in early 2020 with professional career spanning over 20 years as a Quality Assurance (QA) professional in the Pharmaceutical, Biotechnology, and Clinical Research industries. As a QA Specialist at Abbott Laboratories in Abbott Park, IL she received a division research and development award of excellence. Following completion of graduate school, she worked as a Clinical Project Assistant developing custom IVRS/IWRS products for pharmaceutical/biotechnology clinical trials which lead to a position as Global Quality Assurance Manager at Medpace Reference Laboratories, Inc based in Cincinnati, OH. as the for a Clinical Research Organization's central laboratory. The laboratory supported cardiovascular, diabetes, and other metabolic disease clinical trials. She served as an independent advisor to all departments for QA-related subjects, including analytical and IT validation. At Medpace she provided strategic QA direction for both analytical and IT, converging globally distant laboratories in USA, EU, India, and APAC into one functional department for which Kiana received several awards for supporting the company’s global centralization and operational excellence. After her family relocated, Kiana joined PharmaForce, Inc., a sterile injectables CDMO, where she established and managed QA support programs for multi-site parenteral drug manufacturing facilities with expansion, remediation, and validation projects.
Kiana obtained her B.S. in Biology and B.S. in Environmental Health Sciences at Purdue University, IN., followed by a M.S. in Clinical Chemistry at Finch University Health Sciences/The Chicago Medical school.
Denny Thompson
Denny Thompson
Denny joined LIB Therapeutics as the Controller in 2022 to lead the Finance & Accounting departments. He is continuously looking for ways to improve processes and gather valuable insights from data to anticipate future needs.
Prior to LIB Therapeutics, Denny served as a Financial Planning & Analysis Manager in the long-term care industry. He developed innovative planning & analysis tools for various departments such as Treasury, Accounts Payable, Accounts Receivable, and Operations. He has extensive experience in creating and conducting financial modeling, facilitating multiple acquisitions.
Denny received his Master of Science in Finance & Economics from West Texas A&M University and his Bachelor of Science in Business Economics from the University of Louisville.
Advisors
Frederick J. Raal
Frederick J. Raal
Professor Derick Raal is Professor and Head of the Division of Endocrinology and Metabolism and Director, Carbohydrate and Lipid Metabolism Research Unit, Faculty of Health Sciences at the University of the Witwatersrand, Johannesburg, South Africa. After obtaining his MBBCh degree cum laude in 1981, he obtained his Master of Medicine and his PhD in 2000 and his Doctor of Science in 2022. Professor Raal has received numerous postgraduate awards including the TH Bothwell Research Prize, the FJ Milne award, and the University of the Witwatersrand Vice Chancellor’s Research Award in 2015.
He is a NRF A-rated scientist, was recognized as a Web of Science highly cited researcher for 2021, and has authored or co-authored over 350 original articles and book chapters and has reviewed for several international journals including the New England Journal of Medicine, the Lancet, Circulation, and Atherosclerosis. He is a committee member of the homozygous FH International Collaborators registry as well as a member of the steering committee of the European Atherosclerosis Society FH Studies Collaboration (EAS FHSC). He is on the Editorial Board of Atherosclerosis and is a board member of the International Atherosclerosis Society.
Professor Raal is particularly interested in lipids and lipid disorders and has been integrally involved in the management of familial dyslipidaemia, particularly heterozygous and homozygous familial hypercholesterolaemia (FH). The major focus of his research remains the clinical, biochemical, genetic and therapeutic management of this condition and he continues to conduct studies with novel therapies such as PCSK9-inhibitors and ANGPTL3-inhibitors in this patient group.
Wolfgang Koenig
Wolfgang Koenig
Deutsches Herzzentrum München, Technische Universität München, Munich, Germany
Wolfgang Koenig is a Professor of Medicine/Cardiology. A former Director of the WHO-MONICA Augsburg Myocardial Infarction Registry, he has held multiple clinical positions at the University of Ulm Medical Center. In April 2015 he joined the Deutsches Herzzentrum München, where he is the Head of the Cardiometabolic Unit.
Professor Koenig serves on the steering committee of multiple large clinical trials. His research includes the molecular basis of atherothrombogenesis, and the clinical epidemiology of cardiovascular disorders, focusing on the identification and evaluation of new biomarkers for cardiometabolic diseases.
He has published more than 1000 papers in peer-reviewed journals. Between 2008 and 2017, he ranked sixteenth among the most frequently cited German speaking researchers in cardiovascular disease and has an H-Index of 115. He is a member of the Editorial Board of “Clinical Chemistry” and Associate Editor of “Cardiovascular Drugs and Therapy”.
In 2014 he was given the Rudolf Schönheimer Award from the German Atherosclerosis Society, in 2019 he received the degree of Adjunct Professor from the Medical University of Vienna and in 2020 he was awarded the Paul Morawitz prize from the German Cardiac Society.
Meral Kayikcioglu
Meral Kayikcioglu
Professor Kayikcioglu is Director of Lipids and Prevention Clinic, Department of Cardiology, Ege University School of Medicine, Izmir, Turkey. She is also Director of Premature Myocardial Infarction Clinic and Consultant Cardiologist for the Pulmonary Hypertension and Rare Disease Clinic.
Prof Kayikcioglu obtained her MD at Ege University School of Medicine, where she also completed her post graduate training in Internal Medicine and Cardiology.
Prof Kayikcioglu is active in a number of national and international societies including the National Cardiovascular (CV) Disease Prevention European Society of Cardiology (ESC) serving as Coordinator for Turkey between 2009-2022. She has been the deputy ambassador of MENA and India Regions of ESC since 2018 and has been a member of ESC-EORP Oversight Committee and ESC Global Affairs Committee since 2018.
Prof Kayikcioglu has been the Associate Editor of Archives of the Turkish Society of Cardiology since 2016 and chairs the national registries on CV and Rare Diseases including familial hypercholesterolemia (A-HIT 1 and A-HIT 2); the registry of premature myocardial infarction in Turkey (A-HIT 3) and ARTEMIS (registry of peri-partum CMP) and is the national coordinator for EAS of FHSC (Familial Hypercholesterolemia Studies Collaboration). She actively collaborates with the Turkish Ministry of Health on several CV prevention projects.
Prof Kayikcioglu has H-index of 34, i10-Index of 93 and has published more than 180 publications in peer reviewed journals.
LDL-C, CVD & PCSK9
LDL-C and CVD
LDL-C is one of the major modifiable, and clinically validated, risk factors for atherosclerotic cardiovascular disease (CVD). Atherosclerosis, fatty build up in the arteries supplying blood to the heart, brain and legs, leads to CVD which includes heart attacks, angina, heart failure, stroke and peripheral arterial disease (PAD). CVD is still the leading cause of morbidity and mortality in the world and continues grow due to aging populations, increasing obesity and diabetes. It is no longer just a disease found in westernized, affluent societies but now a major concern, and the leading cause of death in rapidly westernizing countries such as India and China. CVD is projected to result in more than 22 million deaths over the next 15 years.
Over the last 30 years, mostly since the introduction of the first effective, safe and mostly well tolerated LDL-C lowering drugs called ‘statins’, large reductions in all types of CVD events and death have been well established by numerous well controlled trials. These trials have demonstrated that people with not just very high or high LDL-C reduce their risk of CVD but those with other risk factors such as prior heart attacks or stroke, diabetes, high blood pressure and smoking with lower LDL-C levels receive as much benefit. Studies have also shown that further LDL-C reductions in people already on statins and other LDL-C lowering drugs achieve even greater reductions in CVD with the new drugs called PCSK9 inhibitors.
The data generated over the last 30 years is so strong and consistent, that an accepted mathematical relationship exists for drugs like statins, ezetimibe and PCSK9 inhibitors which all lower LDL by increasing it removal from the blood stream, that for every 40 mg/dL reduction in LDL-C there is 22% decrease in CVD events in the next 2 to 3 year period. Furthermore, studies show that this reduction in risk increases the longer the LDL-C remains decreased.
LDL-C TREATMENT GUIDELINES: Based on cardiovascular outcome trials (CVOTs) National and International guidelines for prevention and reduction in CVD throughout the world have set lower and lower LDL-C goals for patients and doctors depending on the presence of other risk factors such as prior CVD, diabetes, kidney function, inherited forms of high cholesterol and age. Based on the most recent European, and many other countries, guidelines for patients with CVD or at very high risk for CVD, if LDL-C is >55 mg/dL even on statins, additional reductions of 50% or more are recommended. For these patients more effective and patient friendly PCSK9 inhibitors provide an opportunity to achieve these new lower LDL-C goals.
PCSK9
Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a circulating protein secreted mainly by the liver, kidney and gut, that plays a significant role in the recycling of hepatic receptors (LDLRs). The LDLR is like an oil terminal and is responsible for binding and clearing the LDL in the blood stream and delivering its cholesterol to the liver cells where it is used for a number of important by-products in the body. After delivering LDL into the cell the LDLR recycles about 100 times delivering more and more LDL-C. LDL has no known function in the blood stream which acts only as a means to transport the contents of LDL, which is mostly cholesterol and some other fats and fat soluble vitamins, somewhat like an oil tanker transporting oil through the ocean, from one place to another. Just like an oil tanker if not unloaded safely and within a finite time LDL can break down and release its contents into the blood stream where the cholesterol will lead to damage of the arteries.
PCSK9 was discovered in 2003 in a patient with an inherited form of high cholesterol and very early CVD, called Familial Hypercholesterolemia (FH). FH was known at the time to be caused either by a defect in the LDLR or a protein on LDL that was responsible to attaching LDL to the LDLR that prevented LDL from being cleared from the blood stream. However this patient with FH had neither defect but had high levels of a little known protein in the circulation called PCSK9. Further studies showed that PCSK9 attached, along with LDL to the LDLR in the liver, preventing it from recycling and to be prematurely destroyed, resulting in very high LDL-C in the blood, blockages in the arteries, and CVD. Further studies showed that people with inherited low PCSK9 levels had low LDL-C and very low risk of CVD. A number of companies developed highly specific monoclonal antibodies (mAbs) that bound to, and inactivated, PCSK9 and by 2009 studies in patients demonstrated they were very effective at blocking PCSK9, restored LDLR recycling and reduced LDL-C in the blood stream. These mAbs, usually self-injected every 2 weeks, also proved very well tolerated and had excellent safety. In 2015 two such mAbs, Repatha and Praluent, were approved worldwide for use by patients.
Lerodalcibep while not a mAb, works in a very similar way to monoclonal antibodies as it too binds specifically to PCSK9 in the blood stream and blocks it from attaching to the LDLR, increasing LDLR recycling, increasing LDL-C clearance, and lowering LDL-C.
Pipeline
Novel platform
Small Binding-protein Alternative to Monoclonal Antibodies
Adnectins are a class of targeted biologics derived from the tenth type III domain (10Fn3) of the abundant extracellular protein fibronectin, which mainly functions in the body to bind cells together. 10Fn3-based variants have been developed to bind protein targets such as PCSK9 with high affinities and specificities. Adnectins function in a very similar manner to monoclonal antibodies but provide an alternative protein scaffold that aims to overcome limitations of monoclonal antibody technology. Due to their small size they need to be linked to a larger molecule, called a PK extender, to allow them to remain and work in the blood stream for a longer time.
LIB003 (Lerodalcibep)
LEAD ASSET: Lerodalcibep (LIB003) is being developed as adjunct therapy for patients who on diet and maximally tolerated statin who require additional LDL-C reduction. Lerodalcibep, a small volume (~1 mL), once monthly subcutaneous injection consists of a PCSK9-binding domain and human serum albumin (HSA) as the PK extender.
In a phase 2 trial of 12 weeks lerodalcibep was shown to be safe and highly effective in statin treated patients, reducing LDL-C >75% and continuously suppressing PCSK9 >80% with monthly (Q4W) SC dosing of 300 mg in ~1 mL. In a 52 week phase 2b study lerodalcibep maintained consistent LDL-C reductions, with good tolerability and safety. A large, comprehensive global Phase 3 program in over 2,500 patients is well underway in patients with CVD, high-risk for CVD, Heterozygous FH and Homozygous FH (see clinicaltrials.gov).
LIB002
ADDITIONAL ASSETS: LIB002 is a dual adnectin consisting of the anti-PCSK9 adnectin, in tandem with a second adnectin which binds to endogenous albumin in a patient’s bloodstream. As shown in non-human primates when given SC it works similarly to lerodalcibep. LIB002, with a combined size of only 22 kDa and ability to be manufactured inexpensively in a bacterial system, has the potential for development as an oral drug.
News & Events
News & Press Releases
LIB Therapeutics and Hasten Biopharmaceutical Company Announce $325 Million StrategicCollaboration to Develop and Commercialize Lerodalcibep in Greater China
LIB Therapeutics Appoints David Cory as Chief Executive Officer as Lead Clinical Programs Achieve Phase 3 Completion
LIB Therapeutics Announces Positive Results from the Phase 3 Long-term efficacy andsafety of Lerodalcibep in heterozygous familial hypercholesterolemia (LIBerate-HeFH) trial.
Contact
For more information, email us at info@libtherapeutics.com.
LIB Therapeutics
5375 Medpace Way
Cincinnati, OH 45227-1543
1 (800) 345-2032
