Dyax Corp. (NASDAQ:DYAX) today announced positive results from both preclinical studies of the investigational product DX-2930 and its biomarker assay program for detection of contact system activation of plasma kallikrein (pKal). Data were presented at the 55 th American Society of Hematology (ASH) Annual Meeting and Exposition taking place December 7-10 in New Orleans, LA. DX-2930 is Dyax’s fully human monoclonal antibody inhibitor of pKal. Dyax is developing DX-2930 to be a long-acting prophylactic agent that prevents hereditary angioedema (HAE) attacks. Development plans include a dosage formulation that will permit infrequent self-administration by small volume, subcutaneous injection. DX-2930 is currently being studied in a placebo-controlled, dose-escalation Phase 1 trial in healthy subjects. Results from this study are expected in the first quarter of 2014. “We are excited to be presenting important data at ASH describing the identification, characterization and activity of DX-2930. A key finding from ex-vivo experimental studies is the observation that DX-2930 and ecallantide can be compared as inhibitors of pKal,” said Burt Adelman M.D., Chief Medical Officer and Executive Vice President of Research and Development at Dyax. “The successful development of ecallantide has clearly demonstrated that pKal is a valid target. We are leveraging this knowledge to develop DX-2930.” Dyax currently markets KALBITOR ® (ecallantide) for the treatment of acute HAE attacks in patients 16 years of age and older. “These results provide important early insight into the work being done at Dyax to develop a new preventative treatment option for patients with HAE,” said Gustav Christensen, President and Chief Executive Officer of Dyax. “The Phase 1 clinical study of DX-2930 remains on track to be completed in January and results are expected in the first quarter of 2014.” Dyax’s scientists presented three posters at the meeting. A summary of data presented is below: Title: Comparison of Plasma Kallikrein Inhibition by the Endogenous C1-Inhibitor Versus DX-2930, a Monoclonal Antibody Inhibitor Abstract #: 1066 Summary: In this preclinical study, investigators compared the kinetics and binding properties of C1 inhibitor (C1-INH) and ecallantide to that of DX-2930. C1-INH is a serpin and a key endogenous, protein-based inhibitor of pKal activity. HAE is caused by autosomal dominant mutations in the C1-INH gene resulting in functional protein levels that are approximately 30% or less than normal. Inadequate levels of C1-INH permit uncontrolled pKal-mediated generation of bradykinin resulting in tissue swelling characteristic of an HAE attack. The study results demonstrate that DX-2930 binds pKal assembled on endothelial cells more potently than C1-INH, suggesting that DX-2930 is effective against the cell-bound form of pKal. Endothelial cell bound pKal may explain why HAE attacks are localized to specific sites of the body. Additional studies also demonstrate that DX-2930 and ecallantide can be compared as inhibitors of pKal. Title: Discovery and Characterization of a Highly Specific Antibody Inhibitor of Plasma Kallikrein Abstract #:1067 Summary: In this report, investigators describe the discovery and preclinical evaluation of DX-2930 as a long-acting inhibitor of pKal proteolytic activity. Study results demonstrate that DX-2930 is a potent inhibitor of pKal (Ki=125 pM) that does not bind prekallikrein or any other serine protease tested. In a preclinical model, DX-2930 reduced carrageenan-induced edema in a dose and time dependent manner. Moreover, pharmacokinetic studies following subcutaneous injection in non-human primates demonstrate that DX-2930 has a half-life of 12.5 days. These results suggest that DX-2930 will also have a long half-life in humans and thus the potential for prophylactic inhibition of pKal activity for the therapeutic treatment of HAE. Title: A Biomarker Assay for the Detection of Contact System Activation Abstract #: 2347 Summary: In this study, investigators successfully developed and evaluated a Western blot assay that can detect the presence of intact (1-Chain) and cleaved (2-Chain) high molecular weight kininogen (HMWK) in human and non-human primate plasma samples. HMWK is an important pKal target and the appearance of 2-chain HMWK is a well-recognized effect of pKal action. The vasoactive agent bradykinin is released from HMWK by this action of pKal. In patients with HAE, uncontrolled generation of bradykinin causes HAE attacks that are characterized by painful tissue swelling. Inhibition of pKal action can prevent bradykinin generation. The Western blot assay system was used to compare plasma from HAE patients at basal and attack state with plasma from normal individuals. When compared to normal plasma, 2-chain HMWK levels were elevated in basal HAE patient plasma and were even higher in attack plasma. These results confirm that HMWK cleavage is a useful biomarker for pKal-mediated disease. This assay system was next used to document DX-2930 activity ex vivo in plasma obtained from non-human primates that had received various doses of DX-2930 by subcutaneous injection. Results demonstrate that DX-2930 prevented pKal activity following activation of the contact system by adding kaolin to each sample. The inhibitory effect of DX-2930 was time and dose dependent. These data support the use of this assay system during the development of DX-2930 and as a tool to examine the possible role of contact system activation in other pKal-mediated diseases. About DX-2930 Discovered using Dyax’s proprietary phage display technology platform, DX-2930 is a novel, fully human monoclonal antibody inhibitor of pKal. Uncontrolled pKal activity leads to excessive generation of bradykinin, a vasodilator thought to be responsible for the localized swelling, inflammation and pain characteristically associated with HAE. Preclinical studies suggest that DX-2930 will have a long half-life in humans, offering the potential for a long-acting and sustained therapeutic effect with less frequent dosing. Dyax is currently developing DX-2930 as a subcutaneous injection for the prevention of HAE attacks and the candidate is currently in a Phase 1 clinical trial.
About KALBITORKALBITOR is a pKal inhibitor indicated for the treatment of acute attacks of HAE in patients 16 years of age and older. KALBITOR, which was discovered and developed by Dyax, is the first subcutaneous treatment available in the U.S. for treating acute HAE attacks. Important KALBITOR Safety Information Anaphylaxis has been reported after administration of KALBITOR. Because of the risk of anaphylaxis, KALBITOR should only be administered by a healthcare professional with appropriate medical support to manage anaphylaxis and hereditary angioedema. Healthcare professionals should be aware of the similarity of symptoms between hypersensitivity reactions and hereditary angioedema and patients should be monitored closely. KALBITOR should not be administered to patients with known clinical hypersensitivity to KALBITOR. For more information about KALBITOR, including full prescribing information, visit www.KALBITOR.com. About Hereditary Angioedema (HAE) HAE is a rare acute inflammatory condition characterized by episodes of severe, often painful swelling affecting the extremities, gastrointestinal tract, genitalia, and larynx. HAE is caused by low or dysfunctional levels of C1 esterase inhibitor (C1-INH), a naturally occurring molecule that inhibits plasma kallikrein, a key mediator of inflammation, and other serine proteases in the blood. HAE is estimated to affect up to 1 in 50,000 individuals. Learn more at www.HAEHope.com. About Dyax Dyax is a fully integrated biopharmaceutical company focused on the discovery, development and commercialization of novel biotherapeutics for unmet medical needs. The Company's key value drivers are the KALBITOR business, DX-2930 and Dyax's Licensing and Funded Research Program (LFRP). For additional information about Dyax, please visit www.dyax.com. Disclaimer This press release contains forward-looking statements, including statements regarding the prospects for the Phase 1 clinical trial for DX-2930. Statements that are not historical facts are based on Dyax’s current expectations, beliefs, assumptions, estimates, forecasts and projections about the industry and markets in which Dyax and its licensees compete. The statements contained in this release are not guarantees of future performance and involve certain risks, uncertainties and assumptions, which are difficult to predict. Therefore, actual outcomes and results may differ materially from what is expressed in such forward-looking statements. Important factors which may affect future performance include the risks that: DX-2930 may not show sufficient therapeutic effect or an acceptable safety profile in clinical trials or could take longer to gain regulatory approval than Dyax expects or may never gain approval; others may develop products superior to KALBITOR or DX-2930; KALBITOR and/or DX-2930 may not gain market acceptance; Dyax is dependent on the expertise, effort, priorities and contractual obligations of third parties in the manufacture, marketing, sales and distribution of KALBITOR and DX-2930; and other risk factors described or referred to Item 1A, “Risk Factors” in Dyax’s most recent Annual Report on Form 10-K and other periodic reports filed with the Securities and Exchange Commission. Dyax cautions investors not to place undue reliance on the forward-looking statements contained in this release. These statements speak only as of the date of this release, and Dyax undertakes no obligations to update or revise these statements, except as may be required by law.
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