Therapeutic Editing™

A Powerful Approach to Treating and Curing Diseases

ETAGEN’s Therapeutic Editing™ oligomers specifically bind to and permanently correct disease-causing nucleic acid sequence variants in tissues. We employ chemically-modified DNA oligomers (ETAMERS™) that act as both the guide and template for triggering precise editing by the endogenous DNA repair machinery, addressing the need for a more simple and specific editing platform for in vivo therapeutic applications. ETAMERS create precise repairs without causing undesired insertions and deletions.

ABOUT ETAGEN

ETAGEN Pharma was founded in 2014 by leaders in Therapeutic Editing™ Dr. Tod Woolf and Dr. Richard Hogrefe. ETAGEN’s goal is to correct disease by selectively editing out mutated sequences and to prevent disease by editing in protective genomic variants in tissues. ETAGEN is headquartered in Massachusetts, with chemical synthesis performed by TriLink Biotechnologies in San Diego, California.

MANAGEMENT

Tod Woolf, Ph.D.

Co-Founder

Dr. Woolf co-authored the first article using the term Therapeutic Editing™ and demonstrating efficient Therapeutic Editing in a model cellular system in 1995. Dr. Woolf has developed and commercialized innovative biomedical platforms and products employed throughout the biopharmaceutical industry including mRNA Therapeutics™, Stealth™ RNAi, Self-Delivering rxRNA™ and Next Generation Antisense™. Dr. Woolf completed his Ph.D. thesis in Professor Doug Melton’s laboratory at Harvard University. He co-founded and served as CEO at Sequitur (acquired by Life Technologies) and co-founded RXi Pharmaceuticals with Prof. Craig Mello. His teams have raised over $50M in equity financing and generated over $50M in non-dilutive revenues through alliances, grants and research product sales.

 

Peggy Romero, MBA

Senior Director of Business and Technical Operations

Peggy Romero has served as an advisor establishing business and technical operations at successful start-up biotechnology companies including Karyopharm Therapeutics and Verastem. Ms. Romero served as Director of Operations at Sirtris for six years through its acquisition by GlaxoSmithKline. Previously she was a scientist and manager of laboratory operations for eleven years at Mitotix-GPC Biotech.

 

Amy Tata, CPA

Senior Director of Financial Operations

Amy Tata has performed accounting and worked on financial operations at a wide range of firms from startups to Fortune 500 companies. She was Treasurer, Controller, and Principal Accounting Officer at RXi Pharmaceuticals Corporation. In this role she established financial operations and administered the company’s accounting and SEC Reporting. In 2012, she helped bring the RXi public and implemented controls and procedures for compliance with Sarbanes-Oxley. She previously served as an Audit Coordinator at State Street Bank and Grant Thorton.

 

SCIENTIFIC ADVISORS

 

Richard Hogrefe, Ph.D.

Dr. Hogrefe is the CEO of TriLink Biotechnologies, a leading manufacturer of nucleic acid reagents and therapeutics that he co-founded 18 years ago. Dr. Hogrefe performed his graduate work with Prof. Robert Letsinger, the originator of solid support DNA synthesis chemistry. His academic and industrial career has focused on the synthesis of challenging RNA and DNA drugs and probes. He is author of over 40 patents and research articles, and has served on the editorial board of the journal Oligonucleotides. Dr. Hogrefe’s team at TriLink has provided synthetic support to virtually every major player in oligonucleotide therapeutics.

Prof. Eric Kmiec, Ph.D.

Dr. Kmiec founded and directs the Gene Editing Institute at the Helen F Graham Cancer Center and Research Institute in Newark, Delaware and is a Professor at the University of Delaware. He has also served as Director of the Laboratory of Applied Genomics at the Delaware Biotechnology Institute. His lab was the first to achieve genome editing in mammalian cells with oligonucleotides and he has co-authored over 30 patents and 140 research articles in the genome editing field.

Prof. Richard Boyce, M.D./Ph.D.

Prof. Boyce has an appointment at Harvard University with a laboratory at Massachusetts General Hospital. He received his BS from MIT and his MD/Ph.D. from the University of Michigan. He is an expert on gene therapy and genetic diseases and he has served as an advisor to numerous biotechnology companies. Dr. Boyce cloned the dystrophin brain promoter and performed early work with truncated forms of active dystrophin for gene therapy. Prof. Boyce created a baculovirus expression system for mammalian cells that has been broadly commercialized.

James McSwiggen, Ph.D.

Dr. McSwiggen is an expert in translational nucleic acid therapeutics and bioinformatics and serves as the CEO of the RNA Society.  He is a co-inventor on hundreds of patents and patent applications and was the lead inventor on the “McSwiggen” patent that forms the basis of Alnylam’s 3rd Generation Chemistry. He formerly served as a Research Scientist at RaNA, Quark and SIRNA Merck. Dr. McSwiggen completed his post-doctoral fellowship in the laboratory of Nobel Prize winner Prof. Thomas Cech.

THERAPEUTIC EDITING™ PLATFORM AND PROGRAMS

 

PLATFORM

Therapeutic Editing™: A Powerful Approach to Treating and Curing Diseases.

ETAGEN’s Therapeutic Editing™ drugs called ETAMERS™ specifically bind to and permanently correct disease-causing nucleic acid sequence variants in tissues. ETAGEN’s platform employs a single chemically synthesized ETAMERS that acts as both the guide and template for editing. ETAGEN’s approach has the following beneficial properties for therapeutic development:

• Lowest molecular weight editing compound and protein-free
• Readily manufactured by chemical synthesis
• More readily delivered to target tissues in vivo
• Non-immunogenic allowing for multiple dosing
• Creates a precise repair without causing undesired insertions and deletions
• Does not require dangerous dsDNA breaks
• Strong IP protection with freedom to operate

E-Mail ETAGEN to obtain an updated therapeutic platform presentation pdf

DISCOVERY PROGRAMS

INTERNAL*

  • CYSTIC FIBROSIS MUTATION REPAIR
  • PERMANENT EXON SKIPPING for DUCHENNE MUSCULAR DYSTROPHY
  • HEMOPHILIA MUTATION REPAIR
  • EARLY and LATE ONSETALZHEIMER’S PROTECTION
  • DIABETES-OBESITY RESISTANCE
  • PERMA-STATIN™
  • TTR AMYLOIDOSIS MUTATION REPAIR
  • IN VIVO HEMOGLOBINOPATHY MUTATION REPAIR (BETA-THAL AND SICKLE-CELL)
* Kmiec et al.US Patent 7,258,854 B2 exclusively licensed to ETAGEN and ETAGEN patents pending

PARTNERSHIPS

  • ETAGEN is partnering with biopharmaceutical companies and disease foundations to create ETAMER™ leads for multiple indications.

PUBLICATIONS

 

Selected Publications and Patents Relevant to Therapeutic Editing™ by ETAGEN’s Team Members:

Rivera-Torres N, Strouse B, Bialk P, Niamat RA, Kmiec EB. The Position of DNA Cleavage by TALENs and Cell Synchronization Influences the Frequency of Gene Editing Directed by Single-Stranded Oligonucleotides. PLoS One 2014;9: e96483. (demonstrates gene editing with ETAMERS™ is enhanced by site-directed chromosomal cleavage)

Woolf, Tod, Hogrefe, Richard and Lebedev, Alexandre. COMPOSITIONS AND METHODS FOR EDITING NUCLEIC ACIDS IN CELLS UTILIZING OLIGONUCLEOTIDES. Pending Patent, 2014 Priority date. (discloses 3rd generation ETAMER compositions, methods and targets for use in genome and mRNA editing)

Eric B. Kmiec. Is the age of genetic surgery finally upon us?  Surgical Oncology 24 (2015) 95e99. (review on genome editing)

Woolf TM, Chase JM, Stinchcomb D. Toward the therapeutic editing of mutated RNA sequences. Proceedings of the National Academy of Science 92(18):8298-302, 1995. (first paper using the term nucleic acid “editing” in reference to therapeutics and demonstrating  editing of mutated mRNA)

Woolf, TM. Therapeutic Repair of Mutated Nucleic Acid Sequences. Nature Biotechnology, Vol 16:341-344, 1998. (review of earliest therapeutic editing work and generalizing the concept of genome editing by strand-invasion).

Woolf, Tod, Melton, Doug, and Jennings, Charles. Specificity of antisense oligonucleotides in vivo. Proceedings of the National Academy of Science 89:7305-7309, 1992. (first publication demonstrating mechanism of off-target effects with oligonucleotides related to seed sequences)

Woolf, TM.  It’s Not the Size, It’s the Potency. Nature Biotechnology, August 1996, 14, 824, 1998. (invited commentary on the seminal paper of Richard Wagner et al. demonstrating efficient delivery of “naked” chemically modified antisense oligonucleotides to cells in vitro).

Woolf, TM, Wiederholt, KA and Taylor, MF. Sense mRNA Therapeutics. Published Patent Application US 20090093433, filed 1998. (first description of chemically modified mRNA for therapeutics, now commonly employed for delivering editing proteins)

Li Liu, Michael C. Rice and Eric B. Kmiec. In vivo gene repair of point and frameshift mutations directed by chimeric RNA/DNA oligonucleotides and modified single-stranded oligonucleotides. Nucleic Acids Research, Vol. 29:4238-4250, 2001. (first demonstration of the use of 2nd generation chemically modified single-stranded oligonucleotides (ETAMERS) for genome editing in eukaryotic cells)

Ferrara L, Kmiec EB. Camptothecin enhances the frequency of oligonucleotide- directed gene repair in mammalian cells by inducing DNA damage and activating homologous recombination. Nucleic Acids Res 2004;32:5239e48. (early demonstration that genomic DNA strand breakage enhances efficiency of editing by ETAMERS)

Erin E. Brachman, Eric B. Kmi.  Gene repair in mammalian cells is stimulated by the elongation of S phase and transient stalling of replication forks. DNA Repair 4:445–457, 2005. (demonstration that ETAMER editing efficiency can be enhanced by modification of the cells state)

Eric B Kmiec, Howard B Gamper, Michael C Rice. U.S. Pat. No. 7,258,854 B2, Targeted Chromosomal Genomic Alterations with Modified Single Stranded Oligonucleotides (2007) (discloses 2nd generation chemically modified single-stranded therapeutic editing oligonucleotides (ETAMERS), exclusively licensed to ETAGEN)

Kmiec, EB, Gamper, HB, and Rice, MC. US Pat. No. 7,226,785 Targeted Chromosomal Genomic Alterations with Modified Single Stranded Oligonucleotides (2007) (discloses 2nd generation chemically modified single-stranded therapeutic editing oligonucleotides (ETAMERS), exclusively licensed to ETAGEN)

Julia U. Engstrom and Eric B. Kmiec. DNA replication, cell cycle progression and the targeted gene repair reactions. Cell Cycle 7:10, 1402-1414; 15 May 2008. (demonstrates dramatic increase of editing efficiency by ETAMERS in synchronized cells)

Woolf, TM , Samarky, D. and Cardia, J. Self-Delivering RNAi Compounds. Drug Delivery Technology  Vol. 10 No. 7 Sept. 2010. (describes chemistries for achieving self-delivery of oligonucleotides in cells, currently in phase 2 clinical trials)

NEWS

and PRESENTATIONS

May 2017, Tod Woolf talk entitled: “Therapeutic Editing™ Without Programmable Nucleases” at the Genome Editing USA Congress, 10-11 , Joseph B. Martin Conference Center, Harvard Medical School, Boston, USA

An article about ETAGEN was published in the March 31, 2016 edition of BioCentury. See article HERE.

June 29, 2016. ETAGEN will be presenting of a talk entitled: “Optimizing Oligonucleotide Mediated Editing” at private invitation only conference sponsored by a rare disease foundation.

May 17, 2016. ETAGEN CEO Tod Woolf will participate on panel discussion entitled “The Cutting/Editing Edge” beginning at noon. Piper Jaffray GenomeRx Symposium, The InterContinental New York Barclay, 111 East 48th Street, New York, NY 10017.

May 4-5, 2016. ETAGEN CEO Tod Woolf to present a keynote address talk entitled, Cleaving, Expressing and Repairing Nucleic Acids for Therapeutic Applications at the 13th International RNAi/MicroRNAs/Stem Cells & Genome Editing-2016 Boston Meeting.

February 18, 2016. ETAGEN Advisor, Prof. Eric Kmiec, to present a Keynote address entitled, An Historical Perspective on the Development and Principles of Gene Editing Technologies and ETAGEN CEO Tod Woolf to present a talk entitled, Introduction to Genome Editing and Engineering at the Genome Editing & Engineering Conference in San Diego, CA.

October 13, 2015. Gene Editing Institute pioneering DNA surgery. Someday a host of genetic diseases could be curable by editing a patient’s DNA in USA TODAY (Featuring ETAGEN Scientific advisor’s seminal work on genome editing)

November 18, 2015. Berlin, Germany, EuroTIDES. ETAGEN CEO Tod Woolf presented a talk entitled, Oligonucleotide-Directed Therapeutic Editing

June 16, 2015. BIO International Convention partnering conference in Philadelphia. ETAGEN CEO Tod Woolf gave a presentation entitled, “Genome Editing with Chemically Modified Oligonucleotides” at 10:30 a.m.

June 16, 2015. ETAGEN Pharma Launches Single-Agent Therapeutic Editing Platform with Presentation at the 2015 BIO International Convention, Philadelphia, Pennsylvania

March 19th, 2015. IBC Conference on Genome Editing Applications in Boston. ETAGEN CEO Tod Woolf served as a member of the panel discussion on Genome Editing Nuclease Specificity: Defining Off-Target Effects/Using Genome Editing for Therapeutic Applications

 

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