ESBATech's Antibody Fragment Enters Phase I/IIa Clinical Development In Osteoarthritis With The Potential For Disease-Modifying Activity

Main Category: Bones / Orthopaedics
Also Included In: Arthritis / Rheumatology;  Clinical Trials / Drug Trials
Article Date: 09 Jan 2009 - 5:00 PDT

email to a friend   printer friendly   view / write opinions

ESBATech AG, a leading developer of antibody fragment therapeutics, today announced the initiation of the Phase I/IIa clinical development of its anti-TNF alpha antibody fragment ESBA105 in osteoarthritis (OA). This double-blind, randomized, placebo-controlled Phase I/IIa clinical study is designed to investigate the safety, tolerability and efficacy on pain with ESBA105 applied locally via intra-articular administration to patients with severely painful OA of the knee. The multicenter study is initiated at various sites across Switzerland.

Dominik Escher, Ph.D., Chief Executive Officer of ESBATech AG, commented, "As of today, no disease-modifying osteoarthritis drug exists, which is the key unmet need. OA is being increasingly recognized as driven by episodes of local inflammation and thus, TNF alpha represents a highly promising target. TNF alpha is excessively generated in OA by chondrocytes, which are located within the cartilage. Thus, to achieve disease-modifying activity, it is expected that the drug needs to penetrate into the cartilage, which cannot be achieved by the currently marketed TNF inhibitors. With ESBA105, we observe a very efficient penetration into the cartilage. By that, inhibiting TNF alpha can address the major aspects of OA therapy: signs and symptoms and cartilage degeneration. If clinically successful, ESBA105 is uniquely positioned to fill the need to treat OA with a safe and effective local therapy. A disease-modifying drug would revolutionize the treatment of this debilitating disease."

TNF alpha is a cytokine and a key player in inflammation, and has been identified as a major contributor to pain (signs and symptoms) and cartilage degeneration (structure modification), the main clinical characteristics of OA. Current treatments for OA comprise mainly of non-steroidal anti-inflammatory drugs and intra-articular injections of hyaluronic acids and corticosteroids. These treatments, however, are restricted to pain management, but do not address cartilage degeneration. Blocking TNF alpha offers the opportunity to attack both aspects, managing pain and structure modification. Because of the degenerative nature of OA, every year more than 130,000 knee replacement surgeries are performed in the U.S. alone. Similar numbers are seen in Europe and other major markets.

Peter Lichtlen, M.D., Ph.D., Head of Clinical Development at ESBATech AG, added, "Antibody fragments have a number of advantages over whole antibodies, resulting from their smaller molecular weight. In fact, they are capable of penetrating tissues not accessible to conventional monoclonal antibodies, such as avascularized tissues like cartilage. By delivering high amounts of ESBA105 directly to the affected joint, the antibody fragment quickly and efficiently distributes to the relevant sites in the joint. On the other hand, based on the local delivery and the short systemic half life, systemic exposure of ESBA105 is very low as compared to traditional TNF alpha inhibitors. This is a crucial point in OA, which is a non-life-threatening, rather local disease. Therefore, systemic suppression of TNF alpha, as achieved by marketed TNF alpha inhibitors and associated with various safety issues, is not justified for osteoarthritis patients. The molecular properties of ESBA105 are tailored to the needs of patients suffering from local disease. In this initial clinical trial, we will focus on safety and effects on signs and symptoms. However, the ultimate goal for ESBA105 in OA is disease modification."

About Osteoarthritis

OA is a clinical syndrome of severe joint pain and dysfunction associated with joint degeneration, in particular cartilage loss. More than 70 million people in the seven major pharmaceutical markets and 40 million in the U.S. alone are afflicted with OA. The disease occurs more frequently with age and recent data show the OA market to be growing by three percent annually. At this rate the U.S. patient population will grow to 60 million by 2020.

About ESBATech's antibody fragment platform technology

ESBATech is the first and only company to date that has successfully screened and characterized the entire human pool (1.5 million) of naturally occurring variable immunoglobulin (VH and VL) domains to select highly stable, soluble and monomeric single-chain antibody fragment frameworks. ESBATech's unique, scientific approach to stabilize monomeric, single-chain antibody fragments (scFvs) using its proprietary fully-human antibody fragment frameworks has elucidated the drug-like properties of these proprietary scFvs. The company is advancing a pipeline of novel antibody fragment therapeutics for topical and/or local delivery, to ensure safe and convenient patient therapy.

About ESBATech AG

ESBATech AG is a Zurich, Switzerland-based, privately held drug discovery and development company focused on advancing antibody fragments for therapeutic applications. The Company applies its proprietary, fully human single-chain antibody frameworks to generate product candidates against targets of clinical relevance. ESBATech is focused on delivering high concentrations of its therapeutic antibody fragments to the targeted sites, in combination with extremely low systemic load, in order to achieve low risk of systemic drug reactions using topical and local delivery. The Company focuses on three franchises: ophthalmology, rheumatology and respiratory. In ophthalmology, the Company has successfully completed clinical phase I development of ESBA105 administered topically via eye drops for inflammatory eye diseases.

Current venture investors include SV Life Sciences, Clarus Ventures, HBM BioVentures, HBM BioCapital, Novartis Venture Fund, BioMedinvest and VI Partners.

ESBATech AG