Phase III Multi-center, Randomized, Double-masked, Active- and Placebo-controlled Study of Trabodenoson in Adults With Ocular Hypertension or Primary Open-angle Glaucoma

Phase III trial involving topical application, in both eyes, of trabodenoson ophthalmic formulation 3.0% or 6.0% once per day or 4.5% twice per day, placebo twice per day, or timolol 0.5% twice per day for 12 weeks in adult subjects with Ocular Hypertension or Primary Open-Angle Glaucoma.
All subjects who meet the study's enrollment criteria following Screening will undergo washout of all prohibited medications, including their routine glaucoma medications. During the Placebo Run-In Period, placebo is administered twice daily to both eyes in all subjects. During the Treatment Period, study drug is applied to both eyes for a total of 12 weeks followed by an Observation Period of approximately 7 days wherein no study eye drops are instilled.
The purpose of the study is to assess the efficacy, tolerability, and safety of binocular topical application of trabodenoson ophthalmic formulation 3.0% or 6.0% QD or 4.5% BID for 12 weeks.
Timolol is being included in the trial in order to have an active control to ensure the integrity of the trial from an efficacy perspective; the primary comparator for all statistical purposes is the placebo arm.

Start Date01 Sep 2015

Sponsor / Collaborator

Inotek Pharmaceuticals Corp.

NCT01917383

/ CompletedPhase 2

A Phase II Multi-center, Randomized Study to Evaluate the Monocular Addition of Trabodenoson (INO-8875) Ophthalmic Formulation to Latanoprost Ophthalmic Solution Therapy in Adults With Ocular Hypertension or Primary Open-Angle Glaucoma

The purpose of this study is to evaluate the intraocular pressure (IOP) lowering efficacy and the safety and tolerability profile of trabodenoson ophthalmic formulation compared to timolol maleate ophthalmic solution 0.5% in adults with ocular hypertension (OHT) or primary open-angle glaucoma (POAG) who are already receiving treatment with latanoprost ophthalmic solution 0.005% once every evening (QPM).

Start Date01 Aug 2013

Sponsor / Collaborator

Inotek Pharmaceuticals Corp.

NCT01123785

/ CompletedPhase 1/2

A Phase I/II Multi-Center, Randomized, Double-Masked, Placebo-Controlled, Dose-Escalation Study to Evaluate the Tolerability, Safety, Pharmacokinetics, and Pharmacodynamics (Efficacy) of Chronic Twice-Daily Topical Monocular Application of INO-8875 Ophthalmic Formulation in Adults With Ocular Hypertension or Primary Open-Angle Glaucoma

The purpose of this study is to evaluate how tolerable, safe, and effective it is to give INO-8875 eye drops to adults with glaucoma or ocular hypertension.

Start Date01 May 2010

Sponsor / Collaborator

Inotek Pharmaceuticals Corp.

100 Clinical Results associated with Trabodenoson

100 Translational Medicine associated with Trabodenoson

100 Patents (Medical) associated with Trabodenoson

Literatures (Medical) associated with Trabodenoson

11 Feb 2022·Journal of biomolecular structure & dynamics

Structural analysis, virtual screening and molecular simulation to identify potential inhibitors targeting 2'-O-ribose methyltransferase of SARS-CoV-2 coronavirus

Article

Author: Lotvola, Aaron ; Yang, Zeng-Quan ; Manning, Morenci ; Yang, Zhe ; Jiang, Yuanyuan ; Liu, Lanxin ; Bonahoom, Madison

SARS-CoV-2, an emerging coronavirus, has spread rapidly around the world, resulting in over ten million cases and more than half a million deaths as of July 1, 2020. Effective treatments and vaccines for SARS-CoV-2 infection do not currently exist. Previous studies demonstrated that nonstructural protein 16 (nsp16) of coronavirus is an S-adenosyl methionine (SAM)-dependent 2'-O-methyltransferase (2'-O-MTase) that has an important role in viral replication and prevents recognition by the host innate immune system. In the present study, we employed structural analysis, virtual screening, and molecular simulation approaches to identify clinically investigated and approved drugs which can act as promising inhibitors against nsp16 2'-O-MTase of SARS-CoV-2. Comparative analysis of primary amino acid sequences and crystal structures of seven human CoVs defined the key residues for nsp16 2-O'-MTase functions. Virtual screening and docking analysis ranked the potential inhibitors of nsp16 from more than 4,500 clinically investigated and approved drugs. Furthermore, molecular dynamics simulations were carried out on eight top candidates, including Hesperidin, Rimegepant, Gs-9667, and Sonedenoson, to calculate various structural parameters and understand the dynamic behavior of the drug-protein complexes. Our studies provided the foundation to further test and repurpose these candidate drugs experimentally and/or clinically for COVID-19 treatment.Communicated by Ramaswamy H. Sarma.

04 Mar 2021·Expert opinion on investigational drugsQ2 · MEDICINE

Trabodenoson on trabecular meshwork rejuvenation: a comprehensive review of clinical data

Q2 · MEDICINE

Review

Author: Qiu, Tina Guanting

INTRODUCTION:

Trabodenoson is an adenosine mimetic acting selectively at the A1 receptor (A1R) subtype, involved in multiple signaling pathways including matrix metalloproteinase (MMP-2) associated with glaucoma pathological processes. It has been developed as a Phase 3 candidate for the treatment of patients with primary open-angle glaucoma (POAG) or ocular hypertension (OH).

AREA COVERED:

This review summarizes the molecular traits of Trabodenoson in intraocular pressure (IOP) regulations and provides a scientific interpretation of the Phase 2 clinical study results. This article sheds light on the root causes of the two pivotal Phase 3 clinical trial failures in patients with POAG or OH; it further highlights the discovery of MMP-2 in trabecular meshwork (TM) rejuvenation, which has strategic importance in long-term glaucoma patient care.

EXPERT OPINION:

Trabodenoson is a BID glaucoma eye drop with a possible QD dose as maintenance. Its Phase 3 pivotal clinical trials failed at the wrong dose and dosing regimen because of the misinterpretation of the complex IOP results from the Phase 2 monotherapy and combination studies. The future development should focus on the TM benefits whilst unleashing its potential of neural protection through nanoparticle eye drops, medical coating, and sustained release drug delivery.

01 Jun 2020·FEBS letters

Knowledge‐based structural models of SARS‐CoV‐2 proteins and their complexes with potential drugs

Article

Author: Shionyu‐Mitsuyama, Clara ; Shirai, Tsuyoshi ; Ota, Motonori ; Kanaya, Shigehiko ; Nakae, Setsu ; Shionyu, Masafumi ; Hijikata, Atsushi

The World Health Organization (WHO) has declared the coronavirus disease 2019 (COVID‐19) caused by the novel coronavirus SARS‐CoV‐2 a pandemic. There is, however, no confirmed anti‐COVID‐19 therapeutic currently. In order to assist structure‐based discovery efforts for repurposing drugs against this disease, we constructed knowledge‐based models of SARS‐CoV‐2 proteins and compared the ligand molecules in the template structures with approved/experimental drugs and components of natural medicines. Our theoretical models suggest several drugs, such as carfilzomib, sinefungin, tecadenoson, and trabodenoson, that could be further investigated for their potential for treating COVID‐19.

News (Medical) associated with Trabodenoson

23 Jan 2015

·www.biospace.com

Massachusetts’s Inotek Pharmaceuticals Corporation Sets Terms for $65 Million IPO

January 23, 2015 By Riley McDermid , BioSpace.com Breaking News Sr. Editor Eye drop therapeutics biotech Inotek Pharmaceuticals announced terms for its initial public offering Friday, saying in an updated filing with the U.S. Securities and Exchange Commission that it plans to raise $65 million by offering 4.6 million shares at a price range of $13 to $15—or a fully diluted market value of $200 million if calculated at the midpoint pricing range. The clinical stage Lexington, Mass.-based company is developing a small molecule eye drop therapy to treat glaucoma. If it can raise that higher number, it’ll be one of the larger biotech IPOs debuted in the last year. When it does go public, it will join an avalanche of companies such as Juno Therapeutics and Kite that have capitalized on the booming biotech market to push valuations—and payouts—to an all-time high. Inotek initially filed its S-1 with the SEC in November. In that document, it outlined its plans for proof-of-concept drugs and their timelines. “ Inotek is planning an End-of-Phase 2 meeting with the FDA for trabodenoson monotherapy in the first half of 2015 and expects to initiate a Phase 3 program for it in mid-2015,” it said. If that candidate is successful, Inotek has much to gain: Sales of glaucoma drugs in 2013 raked in around $2 billion in the U.S. and $5.6 billion worldwide, according to statistics from IMS Health . In related news, longtime biotech exec and industry guru Stelios Papadopoulos released data Monday showing that 2014 had 22 percent more biotech IPOs than the infamous “bubble” year of 2000, a major metric market watchers will be eyeing as they head boisterously into a new boom year. That data found that there were an “astonishing” 82 biotech IPOs in 2014, a massive increase from the 67 IPOs 2000. But deal size overall was smaller, with capital raised in 2014 clocking in at $5.5 billion, compared to $5.7 billion in 2000. Papadopoulos has been collecting annual biotech IPO data by hand since 1979—a means of data collection most analysts find to be more meticulous and accurate than larger “number crunching” firms like Reuters or Bloomberg that sometimes miss deals. “I consider his data the definitive source of biotech IPO information,” wrote ISI Evercore analyst Mark Schoenebaum in a note to investors that parsed the data. “I have found many other sources, including Bloomberg , to be inaccurate.” Papadopoulos is perhaps best known as the chairman of Biogen Idec and the former managing director of life sciences investment banking division at SG Cowen Securities Corp , from which he retired in August 2006. BioSpace Temperature Poll What Are Your Predictions for the Price Bidding War? The market has been buzzing about an escalating price war between large payers like Express Scripts and Big Pharma. Multiple deals last week showed Gilead forming exclusive pacts and smaller companies like Kite Pharma starting talks early. What do you think will be the effect on prices? BioSpace wants your opinion! var _polldaddy = [] || _polldaddy; _polldaddy.push( { type: "iframe", auto: "1", domain: "biospace.polldaddy.com/s/", id: "what-are-your-predictions-for-price-bidding-war", placeholder: "pd_1421711966" } ); (function(d,c,j){if(!document.getElementById(j)){var pd=d.createElement(c),s;pd.id=j;pd.src=(' '==document.location.protocol)?' ':' ';s=document.getElementsByTagName(c)[0];s.parentNode.insertBefore(pd,s);}}(document,'script','pd-embed')); Read at BioSpace.com Viehbacher also raised the ire of the board by moving to the U.S. for family reasons, spending only about three months out of the year in France. Despite this, he was popular with shareholders because under his tenure company share prices doubled. He also oversaw the acquisition of Genzyme Corporation . Currently Chairman of the Board Serge Weinberg is acting as interim chief executive officer. There has been a lot of speculation about who might take over the top spot. Christophe Weber, chief operating officer of Japan-based Takeda Pharmaceuticals , had been o offered the position, but declined. Other possible candidates have been Pascal Soriot , CEO of AstraZeneca PLC , who also reportedly declined the position, Oliver Bohuon , of medical device maker Smith & Nephew Plc, Eric Cornut , chief ethics officer of Novartis AG (NVS) and Olivier Brandicourt , director of healthcare for Bayer AG . In Sanofi ’s 2013 annual report it indicated that if he was removed from office, Viehbacher was entitled to two years pay. Calculations would be based on the fixed part of his salary at the time of dismissal and the most recently received variable pay award. In 2014 Viehbacher’s fixed pay was 1.26 million euros. His variable pay for 2013 was 1.70 million euros, which made for a total amount of 5.92 million euros. BioSpace Temperature Poll What Are Your Predictions for the Price Bidding War? The market has been buzzing about an escalating price war between large payers like Express Scripts and Big Pharma. Multiple deals last week showed Gilead forming exclusive pacts and smaller companies like Kite Pharma starting talks early. What do you think will be the effect on prices? BioSpace wants your opinion! var _polldaddy = [] || _polldaddy; _polldaddy.push( { type: "iframe", auto: "1", domain: "biospace.polldaddy.com/s/", id: "what-are-your-predictions-for-price-bidding-war", placeholder: "pd_1421711966" } ); (function(d,c,j){if(!document.getElementById(j)){var pd=d.createElement(c),s;pd.id=j;pd.src=(' '==document.location.protocol)?' ':' ';s=document.getElementsByTagName(c)[0];s.parentNode.insertBefore(pd,s);}}(document,'script','pd-embed')); Read at BioSpace.com

IPOExecutive ChangeAcquisition

11 Jun 2010

·www.biospace.com

Inotek Pharmaceuticals Corporation Brings In $18M For Eye Treatments

LEXINGTON, MA--(Marketwire - June 10, 2010) - Highlighted Links Inotek Pharmaceuticals Corp. Inotek Pharmaceuticals Corp., a leader in the development of innovative drug candidates to address significant diseases of the eye, today announced it has closed an $18 million preferred stock financing. Proceeds from the financing will be used to advance Inotek's novel eye-drop INO-8875 through multiple-dose Phase 2 clinical trials in glaucoma. In an earlier Phase 1/2 clinical trial, INO-8875 was shown to significantly reduce intraocular pressure in glaucoma patients. Devon Park Bioventures, a new investor, led the round with participation from existing investors Rho Ventures, Care Capital, Pitango Venture Capital, MedImmune Ventures, and Bio*One Capital. "We are pleased to receive such financial support from Devon Park and our current investors to advance the clinical development of INO-8875, including the initiation of a multiple-dose Phase 2 clinical trial later this month," stated Paul G. Howes, President and Chief Executive Officer of Inotek. "INO-8875 is a first-in-class product candidate with an elegant mechanism of action that differentiates it from currently approved products for glaucoma as well as other candidates in development. As a highly selective adenosine-1 receptor agonist, INO-8875 enhances outflow through the major pathway used by healthy elderly eyes -- the trabecular meshwork -- to reduce intraocular pressure. With continued clinical success, we believe INO-8875 could play an important role in meeting the need for improved treatments for glaucoma." "We believe INO-8875 is one of the most promising glaucoma product candidates in clinical development today," said John Leaman, M.D., Principal at Devon Park Bioventures. "The Inotek team has made considerable progress advancing the candidate to date and we look forward to working with them as INO-8875 moves into later-stage clinical trials." In conjunction with the financing, John Leaman has joined Inotek's Board of Directors. About INO-8875 for Glaucoma Glaucoma is a leading cause of blindness globally, and it is broadly accepted that lowering intraocular pressure (IOP) in glaucoma patients is the only clinically reliable means of slowing the progression of vision loss. Current products for glaucoma, such as prostaglandins, lower IOP by reducing inflow of fluid in the eye or increasing its drainage through a secondary pathway in the eye -- the uveoscleral pathway. As glaucoma advances with age, the eye's trabecular meshwork grows increasingly clogged with protein debris, and the eye can become less responsive to these mechanisms. As such, a significant percentage of patients do not respond adequately to currently approved products, and up to 40% of patients are treated with a combination of products in the hope of achieving targeted reductions in IOP. There remains an unmet need for innovative glaucoma products acting on the trabecular meshwork to provide improved IOP-lowering efficacy. The Company believes INO-8875 has significant potential as an IOP-lowering medicine, either as monotherapy or in combination with other glaucoma products, because it restores outflow of aqueous humor through the trabecular meshwork. As validation of its complementary mechanism to other glaucoma products, INO-8875 has shown substantial additivity of IOP-lowering efficacy when combined with the leading glaucoma product (Xalatan®, Pfizer) in a preclinical model. As a highly selective adenosine-1 receptor agonist, INO-8875 has a novel mechanism differentiating it from currently approved products and other candidates in development for glaucoma in that INO-8875 enhances a natural cellular signaling pathway to clear debris from the trabecular meshwork, resulting in improved outflow. About Inotek Inotek is a leader in the development of innovative drug candidates to address significant diseases of the eye, with a major focus on glaucoma. Inotek's lead product candidate INO-8875 is a potential first-in-class eye-drop product for glaucoma that significantly reduced intraocular pressure (IOP) in glaucoma subjects following single doses applied to the eye in a Phase 1/2 clinical trial. The Company believes INO-8875 will be a breakthrough treatment that can be used alone or combined with other IOP-lowering products because it increases the outflow of aqueous humor through the trabecular meshwork, the primary drainage system used by healthy elderly eyes to maintain normal IOP. The Company is also advancing a broad pipeline of PARP inhibitors and SOD mimetics that alleviate oxidative injury and inflammation, which it believes may address significant unmet medical needs in retinal diseases, such as the dry form of age-related macular degeneration (dry AMD). The Company is located in Lexington, MA. For further information on Inotek, please visit . About Devon Park Bioventures Founded in 2006, Devon Park Bioventures is a healthcare venture capital firm with a primary focus on therapeutics companies. Based in the Philadelphia area, the firm seeks to invest in companies which have significant commercial potential based on proprietary products, attractive clinical development plans and superior management teams. The General Partners of Devon Park have a longstanding history in the biotechnology business, having been lead or co-lead investor in over 25 biotechnology companies over the past 18 years. For additional information, please visit . Company Information: Adam L. Muzikant, Ph.D. Senior Director, Business Development Inotek Pharmaceuticals (781) 676-2100 Media Relations: Sarah Cavanaugh MacDougall Biomedical Communications Email Contact (781) 235-3060 Digg this Bookmark with del.icio.us Add to Newsvine Technorati: glaucoma ocular hypertension trabecular meshwork eye disease ophthalmology venture capital

Innovative DrugFirst in Class

100 Deals associated with Trabodenoson

External Link

KEGG	Wiki	ATC	Drug Bank
D10493	-	-	DB13122

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Glaucoma, Open-Angle	Phase 3	United States	Inotek Pharmaceuticals Corp.	01 Sep 2015

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT01123772 (Pubmed \| Am J Ophthalmol) Manual	Phase 1	-	70	Trabodenoson	fdigrrfjbp(cgzvwojttv) = qsilhyqzyb wiozcfafxs (xynzonjsmt ) View more	Positive	01 Oct 2016
				Placebo	fdigrrfjbp(cgzvwojttv) = eaagckaldo wiozcfafxs (xynzonjsmt ) View more
NCT01123785 (Pubmed) Manual	Phase 2	Glaucoma, Open-Angle \| Ocular Hypertension	-	Trabodenoson	zajrdciujr(fjkqgkwpdz) = dbhguiurfb bjmgzlpmhw (blpzcrajzn )	Positive	01 Oct 2016
				Placebo	zajrdciujr(fjkqgkwpdz) = tojvpshrrx bjmgzlpmhw (blpzcrajzn )
ARVO2013	Phase 1	Well Aging	70	Trabodenoson	zzuixyrpgg(nwpkaikqtl) = reported in one subject (2.8%) (200μg dose, moderate, duration 1 hour and self-limited) wbzjmozpxt (uaywwunanq ) View more	-	01 Jun 2013

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