Transposon Therapeutics, Inc.

Science

Science

Our mission is to develop innovative treatments for LINE-1 associated neurodegenerative disease.

Almost half of our genome is occupied by virus-like elements called “retrotransposons” which have been introduced into our genome over millions of years. Retrotransposons are mobile DNA elements that use a “reverse transcriptase” enzyme to self-replicate and proliferate. Since these activities can be damaging to our cells, our bodies maintain strict control over retrotransposon expression.

Today, the only retrotransposons in our genome that are capable of becoming active are human-specific LINE-1 elements. Abnormal proteins that lead to neurodegenerative diseases, such as tau and TDP-43, can increase the expression of these LINE-1 elements, initiating a cascade of events in the neuron that leads to its dysfunction and death.

Transposon Therapeutics, Inc. is developing inhibitors of LINE-1 reverse transcriptase and other mediators of LINE-1 pathology for the treatment of neurodegenerative disease.

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Approach

Transposon is developing nucleoside inhibitors of LINE-1 reverse transcriptase (NRTI) and other mediators of LINE-1 pathology (e.g., Protein Kinase R inhibitors [PKR]) for the treatment of neurodegenerative disease.

Transposon Pipeline

Asset Indications Discovery Preclinical Phase 1 Phase 2 Phase 3
Orphan Diseases
TPN-101 Progressive Supranuclear Palsy (PSP)
TPN-101 Amyotrophic Lateral Sclerosis (ALS) / Frontotemporal Dementia (FTD)
TPN-101 Aicardi-Goutières Syndrome (AGS)
Phase 2a late 2022
New Indications
TPN-101 Alzheimer's Disease & Others
  In planning

Novel NRTIs To be determined

Novel PKRi Disorders of cognition

Approach

TPN-101


The most potent known inhibitor of LINE-1 reverse transcriptase is currently under study in two Phase 2a clinical trials.
Our lead reverse transcriptase inhibitor, TPN-101, is the most potent known inhibitor of LINE-1 reverse transcriptase and has excellent systemic and brain bioavailability with once daily oral dosing. TPN-101, also known as censavudine, was well tolerated in a 48-week study of over 220 HIV patients.

The current TPN-101 Phase 2a clinical development program is designed to establish proof-of-concept for treating several neurodegenerative diseases with high unmet medical need and evidence for involvement of LINE-1 reverse transcriptase. Biomarkers will be used to measure changes in inflammation and neurodegeneration to establish proof-of-concept along with safety and clinical efficacy assessments.

Expanded Access Policy PSP ALS/FTD AGS

PSP

Progressive Supranuclear Palsy (PSP)

Why TPN-101
PSP is a primary 4R tauopathy, that is, a disease associated with abnormal accumulation of neurotoxic tau proteins. In the PSP brain, LINE-1 expression is increased and correlates with tau neurofibrillary tangles and interferon-related gene expression. Preclinical evidence shows blocking LINE-1 reverse transcription with TPN-101 mitigates neurodegeneration.

Clinical Trial Information
In the US, we are currently conducting a Phase 2a study of TPN-101 in patients with PSP; the study has a 24-week double-blind, placebo-controlled period followed by a 24-week open-label extension period.

For More Information
ClinicalTrials.gov

Approach › TPN-101

PSP

Progressive Supranuclear Palsy
A devastating orphan disease, with mean survival of 6 to 7 years, characterized by early postural instability and falls, vertical gaze palsy, akinesia, rigidity, pseudobulbar palsy, and frontal dysfunction with cognitive and behavioral changes.

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ALS/FTD

Amyotrophic Lateral Sclerosis (ALS) / Frontotemporal Dementia (FTD)

Why TPN-101
TDP-43 proteinopathies are found in most ALS patients (over 90%) and approximately 40% of FTD patients. Loss of nuclear TDP-43 leading to increased LINE-1 expression and reverse transcription is enriched in FTD or ALS patients with mutation of the C9ORF72 gene and associated with neuroinflammation and induction of Type 1 interferons. Preclinical evidence shows blocking LINE-1 reverse transcription with TPN-101 mitigates neurotoxic pathology.

Clinical Trial Information
To evaluate the therapeutic value of TPN-101 for ALS or FTD, our initial clinical study will focus on patients with C9ORF72 mutations. Our Phase 2a study of TPN-101 is currently enrolling in Belgium, France, Germany, Spain and the US. It is a 24-week double-blind, placebo-controlled study followed by a 24-week open-label extension period.

For More Information
AFTD Website
FTD Registry
NEALS Website
NEALS Video: Dr. Merit Cudkowicz
National ALS Registry
Clinicaltrials.gov

Approach › TPN-101

ALS

Amyotrophic Lateral Sclerosis

FTD

Frontotemporal Dementia

The median survival for ALS is 3 years and 9 years for FTD. When ALS and FTD present as co-morbidities, survival is markedly reduced.
ALS is an orphan disease characterized by progressive muscle weakness and loss of ability to speak, eat, move or breathe.

FTD is a progressive frontal / temporal cortex disease associated with behavior and personality changes, emotional problems, difficulty communicating, working or walking.

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AGS

Aicardi Goutières Syndrome (AGS)

Why TPN-101
Genetic mutations of LINE-1 repressing enzymes (e.g., TREX-1, RNASEH2) cause AGS and result in uncontrolled LINE-1 activation with severe interferon-1 autoimmune reaction. Clinical validation of LINE-1 reverse transcriptase as a therapeutic target was demonstrated in a study of AGS patients receiving reverse transcriptase inhibitors (abacavir, lamivudine and zidovudine) which lowered interferon scores and increased blood flow to the brain.

Clinical Trial Information
An open-label, Phase 2a study of TPN-101 in adult and pediatric patients is planned for late-2022 in France, Italy and the UK.

For More Information
Coming soon

Approach › TPN-101

AGS

Aicardi Goutières Syndrome
AGS is an ultrarare severe pediatric disease generally presenting in infancy; many patients do not survive childhood. Neuronal degeneration causes massive brain damage and loss of developmental milestones beginning shortly after birth and can result in heart and muscle damage.

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Approach

Novel NRTIs

Next generation nucleoside reverse transcriptase inhibitors (NRTIs)

Transposon-proprietary NRTIs will allow rapid exploration of new indications in which there is compelling evidence for LINE-1 related pathology.
Transposon employs informatics and pharmacology research to identify neurologic as well as age-related and autoimmune diseases associated with LINE-1 pathology. Transposon’s inhibitor discovery program has developed a robust pipeline of innovative next generation LINE-1 inhibitors which will be deployed to explore selected disease indications with high unmet medical needs.

Approach

PKR

Protein Kinase R

Downstream druggable targets in the LINE-1 pathway, such as Protein Kinase R (PKR), may be additive or synergistic with LINE-1 reverse transcriptase inhibitor treatment.
Protein kinase R (PKR) is elevated in the cerebrospinal fluid of Alzheimer’s Disease patients, and the degree of elevation correlates with severity of cognitive impairment. Knock-out of the PKR gene in mice leads to improved cognition and memory formation. Small molecule PKR inhibitors have been shown to improve memory and cognition in mouse models.

Our PKR inhibitor discovery program evaluates innovative small molecules for the treatment of compromised cognition and memory associated with central nervous system diseases.

Eckard Weber, MD
Eckard Weber, MD
Chief Executive Officer
Bringing > 30 years experience, Eckard specializes in creating biopharm companies, many of which have been acquired or listed on public markets. He is venture partner at Canaan Partners and an advisory partner at Domain Associates. He is an inventor/co-inventor of numerous patents and has published > 130 papers.
Michael Cordingley, PhD
Michael Cordingley, PhD
Chief Scientific Officer
With > 30 years of experience across multiple therapeutic areas, Michael has held R&D positions at Merck and BMS prior to joining BI as Preclinical TA Head Virology and Infectious Disease and SVP, R&D Site Head, and member of R&D international leadership team. He has held positions at the NCI, NIH, and McGill University.
Andrew Satlin, MD
Andrew Satlin, MD
Chief Medical Officer
Andy brings > 20 years of drug development experience and a focus on novel clinical and statistical methods for neurodegenerative disorders. He was EVP and CMO at Intra-Cellular Therapies, held positions at Eisai and Novartis, and was Assistant Professor of Psychiatry at Harvard Medical School and Director of Geriatric Psychiatry at McLean Hospital.
Lynne Rollins
Lynne Rollins
Chief Financial Officer
With > 40 years of experience in healthcare finance and business development, Lynne serves as CFO for several start-up pharmaceutical and medical device companies. Previously, she served 19 years with Baxter Healthcare Corporation with her latest position as VP Finance for the Cardiopulmonary Business.
Walter Bee, PhD
Walter Bee, PhD
SVP Preclinical & Biomarker Development
Walter has > 30 years experience in nonclinical development and preclinical safety testing. He served as VP Toxicology and Regulatory Consulting and Global Head of Safety Assessment and Regulatory Affairs for QPS, LLC. Previously, he held positions with Halozyme, J&J, Scios, CoCensys, and several leading contract research organizations.
Mark Mugerditchian
Mark Mugerditchian
VP Manufacturing
Mark has > 42 years CMC experience. His broad technical background covers several formats of drug substance (small molecule synthesis and biotechnology) and drug product (SVP, LVP, Solid Oral Dose, inhalation, transdermal, diagnostic).  Recent posts include PvP Biologics, Laguna Pharmaceuticals, Sequel, NovaMedica and NovaCardia.
Jay Soto
Jay Soto
Clinical Operations
Jay brings > 20 years experience in development operations, AI and clinical strategy. He has a diverse background, focusing mainly on neurodegenerative disorders, oncology, immunology, and amyloid-related diseases. Prior roles include VP, Clinical Operations at Prothena as well as positions at Pharmacyclics, Janssen Alzheimer Immunotherapy, Elan, and Amgen.
Priya Jambhekar
Priya Jambhekar
Head, Regulatory
Priya brings > 30 years experience in regulatory and quality affairs. She is experienced in early stage to late state development and post approval activities supporting drugs, biologics, medical devices and combination products in several therapeutic areas. Prior roles include head of regulatory affairs for Baxter Critical Care, Ethicon, Alkermis, Paramount Biosciences.
Debra Liebert
Debra Liebert
Chief Development Officer
Debbie brings over 40 years experience and a passion for company creation and drug development. She serves the board of Milestone and is Chair of the board of Mispro. As Managing Director at Domain, she was instrumental in creating companies as well as portfolio management. Previously, she led corporate / drug development at Trega, CancerVax and Atairgin.

Management Team

Eckard Weber, MD
Eckard
Weber, MD

Chief Executive Officer
Michael Cordingley, PhD
Michael
Cordingley, PhD

Chief Scientific Officer
Andrew Satlin, MD
Andrew
Satlin, MD

Chief Medical Officer
Debra Liebert
Debra
Liebert

Chief Development Officer
Lynne Rollins
Lynne
Rollins

Chief Financial Officer
Walter Bee, PhD
Walter
Bee, PhD

SVP Preclinical & Biomarker Development
Priya Jambhekar
Priya
Jambhekar

Head, Regulatory
Mark Mugerditchian
Mark
Mugerditchian

VP Manufacturing
Jay Soto
Jay
Soto

Clinical Operations

Advisory Boards

Scientific Advisory Board

John Sedivy, PhD Chair
Brown University

Kathy Burns, MD PhD
DFCI, Harvard Med School

George Church, PhD
Harvard University

Josh Dubnau, PhD
SUNY at Stony Brook

Rusty Gage, PhD
Salk Institute

Molly Hammel, PhD
Cold Spring Harbor Lab

Clinical Advisory Board

Murali Doraiswamy, MD Chair
Duke University

Adam Boxer, MD
UCSF

Yanick Crow, MD, PhD
Univ. Edinburgh (AGS)

Merit Cudkowicz, MD
MGH

John Ravits, MD
UCSD

Dennis Podlesak
Dennis Podlesak
Chair
Dennis is CEO / Managing Partner of Axcelius LLC and advisory partner to Domain Associates. His board service or CEO leadership has resulted in many successful exits (Tobira/Allergan, Avanir/Otsuka, Corthera/ Novartis, Rightcare Solutions/Cardinal Health, Calixa/ Cubist, Cerexa/Forest, Peninsula/J&J). Previously, he held executive positions at Novartis, Allergan, and SKB.
Brent Ahrens
Brent Ahrens
Director
Brent is a general partner at Canaan focusing on biopharma & medtech investments, many resulting in successful acquisitions. Current Boards include Abyrx, EndoGastric Solutions, Grey Wolf, Pathios, Relievant MedSystems, and ThirtyFiveBio. Previously, Brent held roles at General Surgical Innovations, Ethicon, and IAP Research and has several surgical instrument patents.
Bill Harrington, MD
Bill Harrington, MD
Director
Bill is Managing Partner at Osage University Partners, a venture capital firm investing in university licensees and spinouts where he is responsible for life science investing. Previously, Bill was General Partner at Three Arch Partners. He has invested in > 80 life science companies and serves the boards of Hyalex Orthopedics, Neuros Medical, MediSix Therapeutics.
Daniel Hetu, MD
Daniel Hetu, MD
Director
With 20+ years of investment banking, corporate development, and licensing experience, Daniel manages Lumira Ventures’ Montreal. His activities focus on building therapeutic and medical device companies that impact patient care. Prior to Lumira, Daniel was a senior executive at Shire and Biochem Pharma and an investment banker at a major Canadian Investment Bank.
Keith Katkin
Keith Katkin
Director
Keith brings almost 30 years of pharmaceutical/biotech experience at large cap, small cap and start-up companies. Keith has significant experience in clinical development, sales and marketing as well as business development. After the successful sales of Avanir and Urovant Sciences, Keith now serves on the Board of Directors of Syndax, Emergent BioSolutions and Eledon.
John Pacifico
John Pacifico
Director
With 20+ years as venture capitalist and healthcare CEO, John brings a wide-range of experience to the Board. He is a General Partner at Canaan, founder & CEO of Abyrx and founder & chairman of the board at Kairuku. He serves the boards of Axcelius, PrimeFour, and Aceiss. Previously, he was President & CEO of ORTHOCON®. He is an inventor of 20+ issued or pending patents.
BT Slingsby, MD
BT Slingsby, MD
Director
Founder & Managing Partner at Catalys Pacific, BT is a physician-scientist and biotechnology entrepreneur leading company creation efforts for the firm. Previously, he founded the GHIT Fund – the world’s first public-private fund focused on development of new medicines for low- and middle-income countries. He is an inventor of multiple patents and author of over 50 scientific papers.
Eckard Weber, MD
Eckard Weber, MD
Director and Chief Executive Officer
Bringing > 30 years experience, Eckard specializes in creating biopharm companies, many of which have been acquired or listed on public markets. He is venture partner at Canaan Partners and an advisory partner at Domain Associates. He is an inventor/co-inventor of numerous patents and has published > 130 papers.

Board of Directors

Dennis Podlesak
Dennis
Podlesak

Chair
Brent Ahrens
Brent
Ahrens

Director
Bill Harrington, MD
Bill
Harrington, MD

Director
Daniel Hetu, MD
Daniel
Hetu, MD

Director
Keith Katkin
Keith
Katkin

Director
John Pacifico
John
Pacifico

Director
BT Slingsby, MD
BT
Slingsby, MD

Director
Eckard Weber, MD
Eckard
Weber, MD

Director and Chief Executive Officer

Team

Transposon is powered by world renowned, pioneering scientists, experienced drug development experts, and repeat entrepreneurs.



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