In the small molecule platforms box change to: HIF-PH Inhibitor for Anemia and HPTPß Inhibitor for PAD
Akebia Therapeutics, Inc. in-licenses and develops breakthrough small molecules that deliver significant therapeutic benefits for the treatment of anemia and vascular disease. The company’s lead compound (HIF-PH inhibitor) is scheduled to enter Phase I clinical trials in 2009. Akebia is based in Cincinnati, Ohio, and is backed by a national syndicate of leading investors.
OVERVIEW
Founded in Cincinnati in 2007, Akebia in-licensed its initial drug development programs and assets from Procter & Gamble. These programs have multiple drug candidates with animal proof-of-concept data, and Akebia is currently focused on developing treatments for anemia and vascular disease.
A key differentiator for Akebia is its approach to early stage drug development. Akebia's highly experienced team works closely with an extensive network of world-renowned consultants, ensuring open collaboration involving the best possible expertise for the challenges at hand. In addition, Akebia successfully navigates early-stage drug development by identifying and addressing risks as early as possible in the development process. Consequently, the company is able to pragmatically mitigate the downstream effects of risk early in the process, while also remaining highly focused and efficient in clinical program design and execution.
LEADERSHIP
CEO – Joseph H. Gardner, Ph.D. Dr. Gardner co-founded Akebia in 2007 following twenty-three years of pharmaceutical discovery and development experience at Procter & Gamble Pharmaceuticals. At P&G he created and managed a broad range of functions including: medicinal chemistry, process chemistry, high through-put screening, computational modeling, and early clinical development. Dr. Gardner spent 2 years in Procter & Gamble’s Health Care merger and acquisition group at P&G developing financial models for pharmaceutical products in addition to evaluating drug company pipelines. During his R&D tenure Dr. Gardner contributed to the writing, coordination and review of 20 IND filings on new chemical entity drug candidates. Prior to leaving P&G Dr. Gardner was director of the intellectual property management function which managed the entire patent portfolio for the P&G Pharmaceutical business. He also gained business development expertise, managing discovery licensing for over ten years. Dr. Gardner received his B.S. with honors in Biological Chemistry from Tulane University in 1977, earned his M.S. in Chemistry (1980) from Utah State University and Ph.D. (1983) in Medicinal Chemistry from University of Wisconsin.
CMO – Robert Shalwitz, M.D.
Dr. Shalwitz co-founded Akebia in 2007. Prior to Akebia, Dr. Shalwitz was Vice President of Clinical Development at Reliant Pharmaceuticals, where he led a clinical team which launched and completed numerous clinical trials for the treatment of lipid and cardiac disorders, and which contributed to several FDA filings. Before Reliant, Dr. Shalwitz was Medical Director at Abbott Labs. During his 10-year tenure at Abbott Labs, Dr. Shalwitz’s team gained FDA approval for two NDAs (in lipid and cardiac disease). In addition, he acquired experience in all phases of drug development, from pre-clinical to Phase IV. Complementing his work in clinical development, Dr. Shalwitz has also become very experienced in pharmaco-vigilance and post-marketing medical affairs. Prior to Abbott Labs, Dr. Shalwitz was an academic pediatric endocrinologist for 10 years. His research at Washington University in St. Louis and at the Children’s Hospital of Orange County (CA) focused on glucose and glycogen metabolism. Dr. Shalwitz received an M.D. degree from SUNY Buffalo and a BGS degree from the University of Michigan.
Scientific Advisory Board
Randall Johnson, Ph.D.
UC San Diego
HIF biology
Frank Bunn, M.D.
Harvard Medical School
Clinical hematology
Anatole Besarab, M.D.
Henry Ford Hospital
Clinical nephrology
John Adamson, M.D.
UC San Diego
Clinical oncology
BOARD
Board Members
Chairman John Rice Ph.D., Triathlon Medical Ventures
Director Anupam Dalal M.D., Kearny Venture Partners
Director Campbell Murray M.D., Novartis Venture Fund
Director Paul Weiss Ph.D., Venture Investors, LLC
Director Joseph Gardner Ph.D., Akebia Therapeutics, Inc.
Observer Suzette Dutch MBA, Triathlon Medical Ventures
Observer Daniel Kosoy M.D., Athenian Venture Partners
Observer Mike Pape Ph.D., Sigvion Capital
PIPELINE
Akebia is currently developing an HIF-PH inhibitor for anemia, and a HPTPβ inhibitor for peripheral artery disease (PAD).
ANEMIA TREATMENT
Anemia is the most common disorder of the blood and results from low hemoglobin levels. Though there are many forms of anemia, the most common causes of chronic anemia are iron or vitamin deficiency, kidney disease, chronic inflammatory diseases, and cancer treatment from chemotherapy or radiation. Symptoms of anemia can include dizziness, weakness, and a general reduction in quality of life, particularly in those with severe anemia.  Treatments for anemia depend on both the cause and severity, and may include iron (usually as ferrous sulfate), Vitamin B-12, blood transfusions (in extreme situations), and recombinant erythropoietin (EPO). Before recombinant EPO was developed, blood transfusions were the only type of treatment available to very anemic patients. However, blood transfusions are difficult to administer, and subject to both potential contamination and fluctuations in the available blood supply.
However, EPO has been shown to improve the quality of life for many patients suffering from serious anemia. Akebia’s lead compound, AKB-6548, aims to match the efficacy of recombinant EPO, but in a more cost effective and safer manner, by stimulating the body’s own production of erythropoietin.
ANEMIA MARKET
Akebia’s first indication for AKB-6548 will be the anemia of chronic renal disease. The United States Renal Data System (USRDS) estimates that there are approximately one million patients with end-stage renal disease. Less than half of those patients are treated with recombinant EPO, and this accounts for the current $4.5 billion market for erythropoiesis stimulating agents (ESA).
An orally bio-available pharmaceutical such as AKB-6548 could significantly expand ESA use to a larger population of patients suffering from anemia associated with chronic renal disease. Oral dosing for an effective anti-anemia agent could also significantly simplify therapy for patients and their physicians.
PAD TREATMENT
Peripheral Artery Disease (PAD) is most commonly caused by atherosclerosis, a hardening or narrowing of the arteries outside the heart or brain. According to the American Heart Association, there are over 8 million Americans who suffer from PAD. Patients who suffer from PAD symptoms often encounter debilitating pain while walking, which can further limit their mobility. In severe cases with critical limb ischemia inadequate blood supply and increased immobility often lead to amputation.  For patients with significant PAD, there are limited treatment options. Doctors may prescribe blood thinners or cholesterol-lowering drugs that prevent the problem from getting worse; however, these treatments do not attack or reverse the existing condition. Stents can be surgically applied as a last resort, but peripheral artery stents are not very successful due to their high rate of restenosis (cell proliferation and re-blockage). Akebia is developing a novel series of compounds to increase the size, number, and strength of peripheral arteries, thereby directly increasing blood flow.
PAD MARKET
Estimated peak sales for Akebia’s new PAD drug (five years post introduction) are in the range of $700M to $900M. These numbers are based on conservative assumptions regarding pricing and market penetration relative to existing patient populations.
TECHNOLOGY/SCIENCE
Akebia is developing pharmaceuticals that augment existing biological mechanisms. The goal is to create a big physiologic effect with small molecules as Akebia’s technologies are based on small molecule enzyme inhibitors. The inhibitors were optimized using all of the latest drug discovery tools, including molecular modeling, structure-based drug design, enzyme and cell-based assays. Akebia has selected these lead molecules and back-up candidates from a large array of molecules – all highly optimized for the biological target. The robust lead selection process used will reduce the risk of failure as Akebia moves its candidates through development and commercialization.
HIF-PH Inhibitor For Anemia
Akebia’s anemia drug development program centers around the Hypoxia Inducible Factor (HIF), a transcription factor that, when active, induces the production of red blood cells via erythropoiesis. HIF is most active during hypoxic conditions. In conditions of normal oxygenation, HIF is quickly hydroxylated via a Hypoxia Inducible Factor prolyl hydroxylase (HIF-PH) and subsequently degraded via the proteasome pathway.Patients with anemia of chronic kidney disease and anemia of inflammatory disease do not produce adequate amounts of EPO to maintain a normal hemoglobin. By inhibiting HIF-PH, Akebia’s small molecule drug stabilizes HIF which, in turn, enhances expression of EPO and other HIF-dependent genes that are required for efficient red blood cell production.Akebia’s drug development program, based on the Hypoxia Inducible Factor prolyl hydroxylase target, has produced orally active compounds that increase endogenous erythropoietin (EPO) production in animals. EPO is the primary peptide hormone that directly stimulates the production of new red blood cells in the bone marrow. The inhibition of the prolyl hydroxylase enzyme provides a potentially safer mechanism to elevate EPO levels than injectable EPO protein.
HPTPß Inhibitor For PAD
Impaired angiogenesis can lead to reduced collateral blood flow and peripheral artery disease (PAD). The specific phosphatase targeted in Akebia’s program is known to regulate angiogenesis signals important for determining the size and growth of new and existing blood vessels. Akebia’s small molecule inhibits this phosphatase, and thereby increases the signaling of two of the natural growth factors for angiogenesis: Angiopoietin 1 (through its receptor Tie2), and VEGF (through its receptor VEGR2). Targeting blood vessel growth in this fashion, by augmenting these signals in hypoxic tissues only, and thereby increasing vessel growth and collateralization, is a novel treatment approach for PAD. Akebia’s phosphatase program targets the HPTPβ enzyme with several classes of compounds that have demonstrated improved collateral blood flow in an ischemic animal model.
NEWS
Akebia News
12.15.08 Akebia announces completion of Series A financing...
9.17.07 Akebia featured in BioWorld Today...
Akebia Therapeutics, Inc.
10151 Carver Road
Suite 205
Cincinnati, OH 45242
USA
Tel: 513.618.0931
Fax: 513.618.0950