XTEN Data From Amunix, Inc. and Versartis, Inc. Featured in Nature Biotechnology as a Novel Platform for Increasing Serum Half-Life of Protein Therapeutics
Published: Nov 16, 2009
REDWOOD CITY, CA and MOUNTAIN VIEW, CA--(Marketwire - November 15, 2009) - Amunix, Inc. and Versartis, Inc. announced today that the scientific journal Nature Biotechnology has published a comprehensive paper entitled "A recombinant polypeptide extends the in vivo half-life of peptides and proteins in a tunable manner." The paper (http://dx.doi.org/10.1038/nbt.1588) describes the design of Amunix's polypeptide sequence XTEN and presents preclinical data for Versartis' product candidates VRS-859 as a monthly-dosed treatment for type 2 diabetes and VRS-317 as a monthly-dosed treatment for growth hormone deficiency.
The published data demonstrate that XTEN, a technology for half-life extension, can provide an effective means for prolonging the in vivo half-life of therapeutic peptides and proteins. With a longer half-life, patients have improved convenience and compliance with comparable efficacy to the drug without XTEN. XTEN is an unstructured recombinant polypeptide that is genetically fused to a peptide or protein. The XTEN sequence has been specifically designed to have low immunogenicity and good manufacturability, making it a generic platform technology applicable to a wide variety of peptide and protein therapeutics. The publication presents, for the first time, the example case of the exenatide peptide fused to XTEN, with a projected human half-life of 139 hours, and preclinical data on human growth hormone fused to XTEN with a half-life in monkeys of 110 hours.
"Based on data from several peptides and proteins fused to XTEN, we expect that XTEN will enable dosing of otherwise rapidly cleared protein drugs at up to monthly intervals in humans," commented Willem 'Pim' Stemmer, Ph.D., Amunix Chief Executive Officer.
"These peer-reviewed results further validate that the monthly-dosed exenatide (VRS-859) and human growth hormone (VRS-317) products provide significant advantages over other approaches on the market or in clinical trials," noted Jeffrey L. Cleland, Ph.D., Versartis Chief Executive Officer.
XTEN has now been successfully fused to more than ten different protein payloads with sizes ranging from small peptides such as exenatide to larger proteins such as growth hormone and Factor VII. Depending on the length of the attached XTEN sequence, data have demonstrated that the serum half-life of a given compound may be tuned to fit its clinical indication. In the case of some payloads, glucagon in particular, extremely long serum half-life may exacerbate toxic side-effects. In addition, extremely long serum half-life can be undesirable in the case where toxicities manifest during treatment, since drug treatment cannot be rapidly withdrawn. Therefore, it is expected that the versatility of various truncations of the XTEN sequence will enable rapid development of precisely tuned therapeutic agents. Although extremely long serum half-life is a concern for some payloads, a large number of payloads benefit significantly from reduced injection frequency, including improvements in patient compliance and expense.
The recombinant nature of XTEN provides several advantages over traditional PEGylation. Genetic fusion of a defined amino acid sequence results in a homogeneous drug compound relative to chemically PEGylated proteins. The overall cost and yield of the final product are also significantly improved for XTEN products, since the need for chemical coupling and purification from multiply PEGylated species, inactive species, and free PEG has been removed. The nonimmunogenic and biodegradable properties of XTEN are expected to yield a significantly improved safety profile relative to PEG.
In addition to the reduced dosing frequency, XTEN products enable room temperature stability and low cost manufacturing. The XTEN properties allow for co-formulation and co-administration of proteins and peptides that are normally incompatible. Versartis and Amunix are also conducting research on combination products for metabolic disease to further exploit these novel properties.
Amunix is focused on the application of its proprietary XTEN protein polymer technology to create a broad spectrum of protein pharmaceutical products with improvements in dosing frequency, compliance and ease of use (via serum half-life increase); safety potential (biodegradability resulting in reduced kidney vacuolation as well as reduced payload immunogenicity); cost of goods (by elimination of chemical conjugation steps); manufacturability (through E. coli soluble cytoplasmic expression, universal purification processes including heat lysis); and formulation (payload stabilization allowing liquid formulation and increased concentration through hydrophilicity). Amunix, Inc. has 28 employees and is located in Mountain View, California. See www.amunix.com for more details.
Versartis, Inc., a Redwood City, California biotechnology company, is developing new therapeutic compounds for the treatment of metabolic diseases and endocrine disorders using XTEN, a novel hydrophilic amino acid sequence that prolongs the half-life of proteins and peptides. Versartis products are designed to provide enhanced stability and less frequent dosing requirements with potentially fewer patient side effects than currently available treatments.
Versartis, a joint venture company between Amunix, Inc. and Index Ventures, owns and develops three novel drug candidates in metabolic diseases and endocrinology that it has licensed from Amunix. Versartis has preclinical proof-of-concept for exenatide and IL-1ra for diabetes, and hGH for growth hormone deficiency. Further information on Versartis can be found at www.versartis.com.
Jeffrey L. Cleland, Ph.D.
Pim Stemmer, Ph.D.