A Phase 2a Study of TPN-101 in Patients With Amyotrophic Lateral Sclerosis (ALS) and/or Frontotemporal Dementia (FTD) Associated With Hexanucleotide Repeat Expansion in the C9orf72 Gene (C9ORF72 ALS/FTD)

This is a Phase 2a study to assess the the safety and tolerability of TPN-101 in patients with Amyotrophic Lateral Sclerosis (ALS) and/or Frontotemporal Dementia (FTD) Associated with Hexanucleotide Repeat Expansion in the C9orf72 gene (C9ORF72 ALS/FTD).

Start Date01 Oct 2021

Sponsor / Collaborator

Transposon Therapeutics, Inc.

100 Clinical Results associated with Censavudine

100 Translational Medicine associated with Censavudine

100 Patents (Medical) associated with Censavudine

Literatures (Medical) associated with Censavudine

01 Apr 2022·Journal of labelled compounds & radiopharmaceuticalsQ4 · MEDICINE

Synthesis of carbon‐14 and stable isotope labeled Censavudine

Q4 · MEDICINE

Article

Author: Samuel J. Bonacorsi Jr. ; Zhongping Shi ; Adrian Ortiz ; Richard C. Burrell ; Tamas Benkovics

Censavudine is a nucleoside reverse transcriptase inhibitor (NRTI) explored clinically by Bristol Myers Squibb for the treatment of human immunodeficiency virus‐1 (HIV‐1). As part of the development process, a carbon‐14 labeled analog was synthesized for use in a human absorption, distribution, metabolism, and excretion (ADME) study. A stable isotope labeled analog was also synthesized for use as a mass spectrum internal standard in bioanalytical assays to accurately quantify the concentration of the drug in biological samples. Carbon‐14 labeled Censavudine was synthesized in 10 steps in a 9% overall yield from carbon‐14 labeled trimethylsilylacetylene. A total of 4.44 mCi of material was prepared with a specific activity of 0.25 μCi/mg. The radiochemical and UV purities were 99% and it met all of the specifications for use in a human clinical study. Deuterium labeled Censavudine was synthesized in two steps in a 68% overall yield from [D4]‐thymine. A total of 237 mg were prepared with a UV purity of 99%.

15 Feb 2022·Accounts of chemical researchQ1 · CHEMISTRY

4′-Modified Nucleosides for Antiviral Drug Discovery: Achievements and Perspectives

Q1 · CHEMISTRY

Article

Author: Chang, Junbiao

Modified nucleosides show therapeutic promise for antiviral therapies. However, issues including the emergence of drug resistance, toxicity, and coinfections have posed new challenges for nucleoside-based antiviral drug discovery, particularly in the era of the coronavirus disease 2019 (COVID-19) pandemic. Chemical manipulation could impact the antiviral potency, safety, and drug resistance of nucleosides. Generally, modified nucleosides are difficult to recognize by intracellular important enzymes as substrates and thus exhibit low toxicity. 4'-Modified nucleosides represent an important subclass of modified nucleosides for antiviral therapies. To prevent the occurrence of drug resistance, 4'-modified nucleosides should have 3'-OH, which should also be chemically unreactive for proviral DNA biosynthesis. The absence of 3'-OH may explain the occurrence of drug resistance for censavudine. The introduction of 4'-substituents improves enzymatic and acidic stability and makes the nucleosides more lipophilic, thus improving cell permeability and bioavailability. Steric hindrance between the 4'-substituent and 3'-OH changes the furanose conformation to the 3'-endo type, in which the oxygen lone pair on the furanose ring could not form an oxocarbonium ion for glycolysis. Currently, seven 4'-modified nucleoside drug candidates such as azvudine (also known as FNC), islatravir, censavudine, balapiravir, lumicitabine, AL-335, and 4-azidothymidine have progressed into clinical stages for treating viral infections. Of note, FNC was officially approved by NMPA in July 2021 for use in adult patients with high HIV-1 virus loads (nos. H20210035 and H20210036), providing an alternative therapeutic for patients with HIV-1. The long-term cellular retention of FNC suggests its potential as a long-lasting pre-exposure prophylaxis (PrEP) agent for preventing HIV-1 infection. Mechanistically, FNC not only inhibited HIV-1 reverse transcription and replication but also restored A3G expression in peripheral blood CD4⁺ T cells in HIV-1 patients receiving FNC. The 4'-azido group in azvudine stabilizes the 3'-C-endo (north) conformation by steric effects and the formation of an intramolecular hydrogen bond with the 3'-OH group, thus decreasing the nucleophilicity of 3'-OH. The north conformation may also enhance the phosphorylation efficiency of FNC by cellular kinases. Encouragingly, FNC, islatravir, and balapiravir show promise for the treatment of coronaviruses, of which FNC has advanced to phase 3 clinical trials in different countries to treat patients with COVID-19 (clinical trial numbers: NCT04668235 and NCT04425772). FNC cured the COVID-19 disease in almost all patients and showed better therapeutic efficacy than remdesivir. In this Account, we provide an overview of 4'-modified nucleoside analogs in clinical stages for antiviral therapies, highlighting the drug discovery strategies, structure-activity relationship studies, and preclinical/clinical studies and also give our perspectives on nucleoside-based antiviral drug discovery.

01 Dec 2021·ChemosphereQ2 · ENVIRONMENTAL SCIENCE & ECOLOGY

Insights into the degradation mechanisms and pathways of cephalexin during homogeneous and heterogeneous photo-Fenton processes

Q2 · ENVIRONMENTAL SCIENCE & ECOLOGY

Article

Author: Song, Shaoxian ; Peng, Lai ; Xu, Yifeng ; Xu, Haixing ; Yang, Chenguang ; Li, Shengjun ; Song, Kang ; Gou, Yejing ; Liu, Chang ; Wu, Xiaoyong

The widespread occurrence of antibiotics in the environment poses a potential threat to human health. The photo-Fenton process has demonstrated better degradation performance compared with the conventional wastewater treatment processes. In this study, the degradation of cephalexin was evaluated comparatively by homogeneous (Fe²⁺/H₂O₂/UV) and heterogeneous (MoS₂@Fe/H₂O₂/UV) photo-Fenton processes. Key influencing factors affecting photo-Fenton performance were assessed, confirming the optimum Fe²⁺ concentration at 0.2016 mg L^-1 and H₂O₂/Fe²⁺ molar ratio at 6. Higher degradation efficiency (73.10%) and pseudo-first-order degradation rate constant (0.0078 min^-1) were achieved with the assistance of MoS₂@Fe as the heterogeneous catalyst. Completely different degradation products were identified in the homogeneous and heterogeneous photo-Fenton processes, with main degradation pathways proposed as β-lactam ring-opening, sulfoxide formation, demethylation, N-dealkylation, decarbonylation, hydroxylation and deamination in the Fe²⁺/H₂O₂/UV system and β-lactam ring-opening, hydroxylation, dehydration, amide hydrolysis, and demethylation and ring contraction in the MoS₂@Fe/H₂O₂/UV system, respectively. The formation of newly identified products might root in the attack on cephalexin from active species (i.e., OH, h⁺, e^-, O₂^-) photoinduced by the MoS₂@Fe catalyst. Results also indicated the importance of understanding the underlying mechanisms and pathways to eliminate the antimicrobial activities of antibiotics in the future.

News (Medical) associated with Censavudine

04 Mar 2026

·www.biospace.com

Transposon Therapeutics’ TPN-101 to be Studied for Extending Healthy Aging under ARPA-H Award for up to $22M

ARPA-H PROSPR program to support the development of TPN-101 to slow aging and help people stay healthy longer SAN DIEGO, March 04, 2026 (GLOBE NEWSWIRE) -- Transposon Therapeutics, a biotechnology company developing therapies for the treatment of neurodegenerative and aging-related diseases, today announced that the Advanced Research Projects Agency for Health (ARPA-H), a federal agency created to support high-impact biomedical projects that could lead to transformative advances in health, has awarded up to $22 million to study Transposon’s TPN-101 for healthy aging under the PROSPR (Proactive Solutions for Prolonging Resilience) program. The award will support a multiphase research and development program to evaluate the ability of TPN-101 to improve aging-related outcomes and other measures of overall health. The ultimate goal of PROSPR is to extend healthspan, which the agency defines as the number of years aging adults live healthy lives and enjoy overall well-being by compressing the frailty and disability that comes with aging into a shorter duration of time near the end of life. “This award represents a transformative opportunity to advance TPN-101 into an entirely new therapeutic category that targets the underlying causes of age-related disease,” said Dennis Podlesak, Chairman and Chief Executive Officer of Transposon. “With no FDA-approved therapies to extend healthspan, we believe TPN-101 has the potential to be at the forefront with a first-in-class approach to preserving function, preventing long-term disease, and extending the years of healthy life.” TPN-101, a first-in-class LINE-1 reverse transcriptase inhibitor, was selected for testing in this program based on emerging evidence that activation of LINE-1 elements in the human genome contributes to cellular aging. LINE-1 elements are a class of retrotransposable elements that in humans are uniquely capable of replicating and moving to new locations within the genome. When this process becomes dysregulated, LINE-1 reverse transcriptase drives the overproduction of LINE-1 DNA, triggering innate immune responses that contribute to neurodegenerative, autoimmune, and aging-related disease pathology. TPN-101 specifically inhibits the LINE-1 reverse transcriptase, thereby reducing the activation of innate immunity and its associated inflammatory and senescence processes. “We have known for years that non-infection related inflammation increases with age and is linked to poor aging outcomes,” says Andrew Brack, ARPA-H Program Manager and creator of the PROSPR program. “Because LINE-1 retrotransposons have recently been reported to increase inflammation as we age, we are excited about the possibility that anti-retroviral therapies, which have the added benefit of a long history of safety in non-diseased populations, will extend healthspan.” “LINE-1 activation sits upstream of numerous age-related pathologies,” said Dr. Andrew Satlin, Chief Medical Officer of Transposon. “This program allows rigorous evaluation of TPN-101 as a treatment to help people stay healthier, stronger, and mentally sharper as they grow older, not by treating diseases one by one but by slowing a biological process that drives aging itself.” Transposon is advancing TPN-101 in late-stage clinical trials for the treatment of neurodegenerative diseases, including progressive supranuclear palsy (PSP), amyotrophic lateral sclerosis (ALS) and Alzheimer’s disease. The pathology of these diseases involves disruption to the normal cellular processes that suppress LINE-1 expression, leading to further increases in LINE-1 activation beyond those seen as part of the aging process. Transposon Therapeutics will collaborate with University of Rochester; Brown University; University of Connecticut; University of Texas Medical Branch, University of Texas Health; and University of Nebraska on the PROSPR project. About Transposon Transposon Therapeutics, Inc. is a clinical-stage biopharmaceutical company focused on developing transformational therapies for the treatment of neurodegenerative and aging-related diseases, including PSP, ALS, and Alzheimer’s disease. The company’s lead clinical compound, TPN-101, is first-in-class to address LINE-1 reverse transcriptase for the treatment of neurodegenerative and autoimmune diseases. The company also has a discovery platform supporting a deep pipeline of novel therapies to address additional indications. CONTACT: Contact: Rick Orr Transposon Therapeutics, Inc. (858) 535-4821 rorr@transposonrx.com

09 Jul 2025

·www.prnewswire.com

Transposon Receives Investment from the Alzheimer's Drug Discovery Foundation to Support Advancement of TPN-101 for the Treatment of Alzheimer's Disease

Building on the positive results of Phase 2 clinical trials in PSP and ALS, Transposon plans to initiate a Phase 2 clinical trial of TPN-101 for the treatment of Alzheimer's disease in Q4 2025 Concurrently, Transposon is advancing TPN-101 in the Phase 2/3 HEALEY ALS Platform trial SAN DIEGO, July 9, 2025 /PRNewswire/ -- Transposon Therapeutics, a biotechnology company focused on developing novel, orally administered therapies for the treatment of neurodegenerative and aging-related diseases, including amyotrophic lateral sclerosis (ALS), progressive supranuclear palsy (PSP), and Alzheimer's disease (AD), today announced that it has secured an investment from the Alzheimer's Drug Discovery Foundation (ADDF) to advance the development of TPN-101 for the treatment of AD. The company expects to initiate a Phase 2 clinical trial to study the effect of TPN-101 in patients with AD by the end of 2025. "We are delighted to be partnering with the Alzheimer's Drug Discovery Foundation to rapidly advance the development of TPN-101 for the treatment of Alzheimer's disease," said Dennis Podlesak, Chairman and Chief Executive Officer of Transposon Therapeutics. "Based on the positive results of our recently completed Phase 2 studies of TPN-101 in both PSP and ALS, we believe TPN-101 has the potential to provide a critically needed treatment option for a wide range of neurodegenerative diseases, including Alzheimer's, ALS, and PSP." In the Phase 2 clinical trial of TPN-101 in patients with PSP, TPN-101 was the first treatment to reduce CSF levels of neurofilament light chain (NfL) compared to placebo, a key biomarker of neurodegeneration in tauopathies such as PSP and Alzheimer's disease. TPN-101 also showed dose-related reductions in interleukin 6 (IL-6) cytokine levels, a biomarker of neuroinflammation that is elevated in PSP and correlates with disease progression and severity. In the Phase 2 clinical trial of TPN-101 in patients with C9orf72-related ALS and/or frontotemporal dementia (FTD), treatment with TPN-101 also reduced levels of NfL and IL-6 in the ALS population and showed a slowing of ALS disease progression as measured by the Revised ALS Functional Rating Scale (ALSFRS-R). "The ADDF has a long history of supporting and investing in approaches to combat the underlying pathology of aging including novel pathways like inflammation," said Howard Fillit, MD, Co-Founder and Chief Science Officer at the ADDF. "Transposon's advancement of TPN-101 to target neuroinflammation and the abnormally activated immune system is one of the many exciting new therapeutic approaches in development for Alzheimer's." Concurrent with the Phase 2 clinical trial to study the effect of TPN-101 in patients with AD, Transposon is advancing TPN-101 in the Phase 2/3 HEALEY ALS Platform trial. Further information about the HEALEY ALS Platform Trial can be found at HEALEY ALS Platform Trial. About the Alzheimer's Drug Discovery Foundation Founded in 1998 by Leonard A. and Ronald S. Lauder, the Alzheimer's Drug Discovery Foundation is dedicated to rapidly accelerating the discovery of drugs to prevent, treat and cure Alzheimer's disease. The ADDF is the only public charity solely focused on funding the development of drugs for Alzheimer's, employing a venture philanthropy model to support research in academia and the biotech industry. The ADDF's leadership and contributions to the field have played a pivotal role in bringing the first Alzheimer's PET scan (Amyvid®) and blood test (PrecivityAD®) to market, as well as fueling the current robust and diverse drug pipeline. Through the generosity of its donors, the ADDF has awarded more than $370 million to fund 765 Alzheimer's drug discovery programs, biomarker programs and clinical trials in 21 countries. To learn more, please visit: . About Transposon Transposon Therapeutics, Inc. is a clinical-stage biopharmaceutical company focused on developing transformational therapies for the treatment of neurodegenerative and aging-related diseases, including PSP, ALS, and Alzheimer's disease. The company's lead clinical compound, TPN-101, is first-in-class to address LINE-1 reverse transcriptase for the treatment of neurodegenerative and autoimmune diseases. The company also has a discovery platform supporting a deep pipeline of novel therapies to address additional indications. About TPN-101 TPN-101 specifically inhibits the LINE-1 reverse transcriptase that promotes LINE-1 replication. LINE-1 elements are a class of retrotransposable elements that in humans are uniquely capable of replicating and moving to new locations within the genome. When this process becomes dysregulated, LINE-1 reverse transcriptase drives the overproduction of LINE-1 cDNA, triggering innate immune responses that contribute to the pathology of neurodegenerative, neuroinflammatory, and aging-related diseases. Contact: Rick Orr Transposon Therapeutics, Inc. (858) 535-4821 [email protected] SOURCE Transposon Therapeutics WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Phase 2Clinical Result

21 Nov 2024

·www.prnewswire.com

Transposon Therapeutics Strengthens and Expands Development Pipeline with the Acquisition of a Portfolio of Novel Nucleoside Analogs for Oncology

Portfolio of nucleoside chemotherapeutics for the targeted treatment of pancreatic cancer, certain other solid tumors and hematologic cancers Builds upon leadership position in developing best-in-class, late-stage nucleoside reverse transcriptase inhibitors for neurodegenerative and autoimmune diseases SAN DIEGO, Nov. 21, 2024 /PRNewswire/ -- Transposon Therapeutics, a biotechnology company developing a platform of novel, orally administered therapies for the treatment of neurodegenerative and aging-related diseases, today announced the acquisition of a portfolio of novel nucleoside analogs from PrimeFour Therapeutics, Inc., a biotechnology company focused on cancer chemotherapeutic agents. The portfolio of novel nucleosides consists of a chemically diverse library of unique analogs. The most advanced lead compounds are nucleosides that cause "synthetic lethality" in cancers characterized by distinct tumor-defined genetic signatures, allowing them to be precisely targeted to the most susceptible cancers with reduced toxicity. These compounds can be targeted towards cancers with newly discovered genetic biomarkers that are present in pancreatic and certain other solid tumors as well as in hematologic cancers, allowing for personalized therapy in those patients most likely to respond to treatment. "This transaction allows us to build upon our leadership in developing first-in-class and best-in-class nucleoside reverse transcriptase inhibitors for neurodegenerative and autoimmune diseases, including ALS, PSP and Alzheimer's disease. We are excited to expand our pipeline to include this portfolio of potent nucleoside chemotherapeutics with significant therapeutic potential against a variety of cancers," said Eckard Weber, M.D., founder and Chief Innovation Officer of Transposon. "We look forward to advancing the lead compounds into preclinical development to target DNA-damage repair deficient cancers, such as pancreatic and colorectal cancers." About Transposon Transposon Therapeutics, Inc. is a clinical-stage biopharmaceutical company developing a platform of novel nucleoside reverse transcriptase inhibitors for the treatment of neurodegenerative and aging-related diseases, including Alzheimer's disease. The company's lead clinical compound, TPN-101, is first-in-class to address LINE-1 reverse transcriptase for treating neurodegenerative and autoimmune diseases. Transposon is advancing TPN-101 into Phase 3 registration studies for the treatment amyotrophic lateral sclerosis (ALS) and progressive supranuclear palsy (PSP), and a Phase 2 proof-of-concept study in Alzheimer's disease. The company also has a discovery platform supporting a deep pipeline of novel therapies to address additional indications. About PrimeFour PrimeFour discovered and developed a class of novel nucleoside analogs that are selectively incorporated into cancer cells with biomarker-identifiable DNA damage repair deficiencies and that, once incorporated into some cancer cells, cause irreversible DNA damage and cancer cell death. Contact: Rick Orr Transposon Therapeutics, Inc. (858) 535-4821 [email protected] SOURCE Transposon Therapeutics WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

AcquisitionPhase 2Phase 3

100 Deals associated with Censavudine

External Link

KEGG	Wiki	ATC	Drug Bank
D10550	Censavudine	-	DB12074

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Aicardi-Goutieres Syndrome	Phase 2	France	Transposon Therapeutics, Inc.	15 Mar 2023
Aicardi-Goutieres Syndrome	Phase 2	Italy	Transposon Therapeutics, Inc.	15 Mar 2023
Aicardi-Goutieres Syndrome	Phase 2	United Kingdom	Transposon Therapeutics, Inc.	15 Mar 2023
Supranuclear Palsy, Progressive	Phase 2	United States	Transposon Therapeutics, Inc.	12 Dec 2021
Amyotrophic Lateral Sclerosis	Phase 2	United States	Transposon Therapeutics, Inc.	01 Oct 2021
Amyotrophic Lateral Sclerosis	Phase 2	Belgium	Transposon Therapeutics, Inc.	01 Oct 2021
Amyotrophic Lateral Sclerosis	Phase 2	France	Transposon Therapeutics, Inc.	01 Oct 2021
Amyotrophic Lateral Sclerosis	Phase 2	Germany	Transposon Therapeutics, Inc.	01 Oct 2021
Amyotrophic Lateral Sclerosis	Phase 2	Spain	Transposon Therapeutics, Inc.	01 Oct 2021
Frontotemporal Dementia	Phase 2	United States	Transposon Therapeutics, Inc.	01 Oct 2021

Clinical Result

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04993755 (PRNewswire) Manual	Phase 2	Frontotemporal Dementia \| Amyotrophic Lateral Sclerosis	42	TPN-101	elwqemjwid(rurystayva) = ffiebarhxp zjeakgncnj (oozecauacm ) View more	Positive	24 Jul 2024
				Placebo	elwqemjwid(rurystayva) = acfcxptaje zjeakgncnj (oozecauacm ) View more
NCT04993768 (PRNewswire) Manual	Phase 2	Supranuclear Palsy, Progressive	-	TPN-101 400mg	unrtpcgbge(dehnhhwvio) = Once-daily oral dosing of TPN-101 was well-tolerated at all dose levels. njsagcmnsi (qjjvsdztlf )	Positive	14 Nov 2023
				placebo

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