flecainide/modafinil (THN102) / THX Pharma - LARVOL DELTA

Theranexus : Theranexus publishes its 2021 full-year results And announces a shift of its strategic focus to rare neurological diseases (Market Screener) - "Drawing on the positive Phase 2 results achieved by its drug candidate THN102 for Excessive Daytime Sleepiness in Parkinson's disease, the company resolutely explored all conceivable partnership options (global or regional licensing agreement, co-development, etc.). However, despite all efforts made during negotiations with several pharmaceutical companies, the discussions proved unsuccessful....The company therefore decided to discontinue the THN102 program..."

Discontinued • CNS Disorders • Excessive Daytime Sleepiness • Parkinson's Disease • Sleep Disorder

THN 102 for Excessive Daytime Sleepiness Associated with Parkinson's Disease: A Phase 2a Trial. (PubMed, Mov Disord) - "THN102 was well tolerated and showed a signal of efficacy at the 200/2 dose, supporting further development for the treatment of EDS in PD."

Clinical • Journal • P2a data • CNS Disorders • Excessive Daytime Sleepiness • Movement Disorders • Parkinson's Disease • Sleep Disorder

"@Lundbeck @Theranexus Deal done for THN102 ?" (@R904571239)

Safety and Efficacy of THN102 in Patients With Parkinson's Disease and Excessive Daytime Sleepiness (clinicaltrials.gov) - P2; N=77; Completed; Sponsor: Theranexus; Active, not recruiting ➔ Completed

Clinical • Trial completion • CNS Disorders • Excessive Daytime Sleepiness • Movement Disorders • Parkinson's Disease • Sleep Disorder

Advances in treatment of narcolepsy (PubMed, Zhejiang Da Xue Xue Bao Yi Xue Ban) - "Pitolisant (a histamine H3 receptor antagonist) and solriamfetol (a norepinephrine reuptake inhibitor) have recently been approved effective for narcolepsy in the United States and the European Union. These new drugs include new hydroxybutyrate preparations (controlled release sodium hydroxybutyrate FT218, low sodium hydroxybutyrate JZP-258), selective norepinephrine reuptake inhibitor (AXS-12), and modafinil combined with astroglial junction protein inhibitor (THN102). This paper reviews the recently approved drugs and potential treatments for narcolepsy."

Journal • Cataplexy • CNS Disorders • Excessive Daytime Sleepiness • Narcolepsy • Obstructive Sleep Apnea • Psychiatry • Sleep Disorder

Efficacy of THN102 (a combination of modafinil and flecainide) on vigilance and cognition during 40-hour total sleep deprivation in healthy subjects: Glial Connexins as a therapeutic target. (PubMed, Br J Clin Pharmacol) - "THN102 seems more efficient than modafinil on vigilance, working memory and executive functions, opening new perspectives in management of hypersomnolence disorders."

Clinical • Journal

Flecainide Plus Modafinil Relieves Sleepiness in Parkinson's (Medscape) - "'So that's kind of unusual that there isn't a dose-dependent effect,' Alberto Espay...commented...Given the modest effects, 'I don't know if this will translate into clinical significance'....Espay said it may be interesting to see if the investigators 'see anything in the data they collected that could speak about predictors of response, as well as predictors of lack of response, so that they can perhaps fine-tune the selection of patients most likely to benefit for the next study.'"

Media quote

"Low dose flecainide + modafinil alleviated excessive daytime sleepiness in #Parkinsons, a new study suggests. https://t.co/nlN7pSpYbU" (@MedscapeNeuro)

CNS Disorders • Excessive Daytime Sleepiness • Movement Disorders • Parkinson's Disease • Sleep Disorder

[VIRTUAL] THN 102, an association of modafinil and low dose flecainide, in the treatment of excessive daytime sleepiness associated with Parkinson’s Disease: a double-blind, placebo controlled study (MDS Congress 2020) - "THN 102 was well tolerated. PD patients with EDS were significantly improved when treated with THN 102. These results warrant further confirmation in future clinical trials."

Clinical • Late-breaking abstract • CNS Disorders • Excessive Daytime Sleepiness • Pain • Parkinson's Disease • Sleep Disorder

Theranexus: THERANEXUS TO PRESENT THN102 RESULTS IN PARKINSON'S DISEASE AT INTERNATIONAL CONGRESS OF PARKINSON'S DISEASE AND MOVEMENT DISORDERS (MDS) 2020 [Google translation] (Zonebourse) - P2, N=75; NCT03624920; Sponsor: Theranexus; "Theranexus...will present the phase 2 results of its THN102 drug candidate in the Parkinson's disease at the International Congress of Parkinson's Disease and Movement Disorders which will take place from September 12 to 16, 2020. This presentation entitled 'THN102, an association of modafinil and low dose flecainide, in the treatment of excessive daytime sleepiness associated with Parkinson's Disease: a double-blind, placebo-controlled study', will be produced...THN102 was well tolerated by these often fragile patients, the reduction in daytime sleepiness, the main efficacy endpoint was successfully achieved and THN102 also strongly increased the proportion of patients no longer presenting daytime sleepiness during the period. processing."

P2 data • Cataplexy • CNS Disorders • Parkinson's Disease • Sleep Disorder

THERANEXUS OBTAINS NON-DILUTIVE FINANCING OF EUR 3.4 MILLION IN THE FORM OF A LOAN GUARANTEED BY THE GOVERNMENT AND TAKES STOCK OF ITS DEVELOPMENTS [Google translation] (Zonebourse) - "The Company has just obtained non-dilutive financing of € 3.4 million....Theranexus also received the accelerated and full repayment of the 2019 Research Tax Credit (CIR) in the amount of € 2 million during the month of May 2020....The positive results of the phase 2 clinical study position THN 102 as the first potential treatment for excessive daytime sleepiness (EDS) in patients with Parkinson's disease....THN 102 could reach sales of more than $ 1 billion with a processing price of more than $ 20,000 in the United States. -United States and 5,000 dollars on average in Europe....Objective of Theranexus is to conclude a partnership with an industrialist promoting the positive results of this phase 2 and ensuring the clinical development of this drug candidate until its commercial exploitation....This partnership is expected by the end of 2020."

Financing • Licensing / partnership • Sales projection • CNS Disorders • Excessive Daytime Sleepiness • Parkinson's Disease • Sleep Disorder

BRIEF-Theranexus FY operating loss widens to 7.4 million euros (Reuters) - "The company’s cash amounted to €7,807 k at March 31 2020. The operating loss increased slightly from -€6,990 k in 2018 to -€7,377 k in 2019. Company is in a position to meet its financial obligations in the coming 12 month. Promising prospects following the recent success of the phase II trial for thn102 in Parkinson’s patients."

Commercial

Theranexus announces the success of its phase II trial for THN102 in Parkinson’s patients [Google translation] (Theranexus Press Release) - P2, N=71; NCT03624920; Sponsor: Theranexus; "Theranexus...has announced the success of its Phase II trial for drug candidate THN102 for Parkinson's disease. Seventy-five Parkinson's patients with debilitating, excessive daytime sleepiness (EDS) were recruited in Europe and the United States. THN102 met the primary efficacy endpoint and significantly increased the proportion of patients no longer suffering from daytime sleepiness for the duration of the treatment...The trial demonstrated the excellent tolerability profile of THN102 for the two doses tested."

P2 data

Theranexus announces the success of its phase II trial for THN102 in Parkinson’s patients (Yahoo Finance) - P2, N=75; NCT03624920; Sponsor: Theranexus; "Theranexus...has announced the success of its Phase II trial for drug candidate THN102 for Parkinson's disease....THN102 met the primary efficacy endpoint and significantly increased the proportion of patients no longer suffering from daytime sleepiness for the duration of the treatment...The aim for Theranexus is now to join forces with an industrial partner to continue developing THN102."

Licensing / partnership • P2 data

Recently Approved and Upcoming Treatments for Narcolepsy. (PubMed, CNS Drugs) - "Treatments for narcolepsy are aimed at improving wakefulness (e.g. modafinil, armodafinil, stimulants), reducing cataplexy attacks (e.g. sodium oxybate, venlafaxine), and treating the symptoms of disturbed nocturnal sleep, sleep paralysis and sleep-related hallucinations (e.g. sodium oxybate)...Pitolisant, an H3R antagonist, and solriamfetol, a dopamine and norepinephrine reuptake inhibitor, are the most recently approved treatments for EDS associated with narcolepsy in the European Union (pitolisant) and the USA (pitolisant and solriamfetol). Several new agents are being developed and tested as potential treatments for EDS and cataplexy associated with narcolepsy; these agents include novel oxybate formulations (once-nightly [FT218]; low sodium [JZP-258]), a selective norepinephrine reuptake inhibitor (AXS-12), and a product combining modafinil and an astroglial connexin inhibitor (THN102). This review summarises the mechanisms of action, pharmacokinetics, efficacy, and..."

Journal • Review

Safety and Efficacy of THN102 in Patients With Parkinson's Disease and Excessive Daytime Sleepiness (clinicaltrials.gov) - P2; N=71; Active, not recruiting; Sponsor: Theranexus; Recruiting ➔ Active, not recruiting

Clinical • Enrollment closed

Theranexus announces its first half 2019 results (Theranexus Press Release) - "Other purchases and external charges increased during the period to €2,905 K up from €2,034 K in the first half of 2018. This increase was driven by the ramp-up of the Phase II program for Parkinson's disease....The Company recently announced the publication of two scientific papers, one focusing on expanding the proprietary library of glial effector cells in the journal ASSAY and Drug Development Technologies, and the other on the clinical pharmacological profile of THN102 in the British Journal of Clinical Pharmacology."

Clinical data • Commercial

A new milestone reached for Theranexus: Inclusion of last patient in phase II trial for THN102 in Parkinson’s patients (Theranexus Press Release) - "Theranexus...recently achieved a new milestone by recruiting the last patient with Parkinson’s disease to its Phase II clinical trial which aims to evaluate the tolerance and efficacy of its drug candidate THN102 on non-motor symptoms of the disease....Parkinson’s disease patients with excessive daytime sleepiness have been recruited across Europe and the United States....We are eagerly awaiting the results for THN102. These are due in Q1 2020..."

Enrollment status • P2 data

Theranexus announces issuance of Chinese patent covering its drug candidate THN102 (Theranexus Press Release) - "Theranexus...today announces the issuance of a Chinese patent for its drug candidate THN102. This patent was granted to the French Alternative Energies and Atomic Energy Commission (CEA) by the Chinese State Intellectual Property Office (SIPO)....This CN 105579041 B patent...protects the drug candidate THN102, which combines flecainide as an anti-connexin agent and modafinil as a psychotropic drug, until 2034. This patent covers a therapeutic composition containing flecainide and modafinil, to treat, for example, excessive daytime sleepiness in patients suffering from Parkinson's disease or narcolepsy, to boost memory in healthy patients..."

Patent

Theranexus provides 2018 full-year results and update on activities (Theranexus Press Release) - "THN102 (modafinil/flecainide combination) is currently undergoing a Phase II clinical trial to treat a triad of non-motor symptoms (sleepiness, attention and cognitive disorders) in Parkinson's disease patients...has already enrolled more than half of its participants in Europe and the United States to date. Results from the trial are expected in the second half of 2019."

Enrollment status • P2 data

Theranexus announces preliminary results of phase II trial of THN102 on narcolepsy patients (Theranexus Press Release) - P2, N=51; NCT02821715; Sponsor: Theranexus; "Theranexus...today announces the preliminary results of its Phase II trial in narcolepsy patients....THN102's safety and tolerability profile has been deemed very satisfactory. However, the results do not indicate any difference in efficacy between THN102 (combination of modafinil and flecainide) and modafinil alone with respect to the trial’s primary endpoint (Epworth Sleepiness Scale)....THN102...currently undergoing a Phase II clinical trial in Parkinson's disease patients....Recruitment is expected to be completed by the end of the first half of 2019."

P2 data • Trial status

Safety and Efficacy of THN102 in Patients With Parkinson's Disease and Excessive Daytime Sleepiness (clinicaltrials.gov) - P2; N=60; Recruiting; Sponsor: Theranexus; Trial completion date: Oct 2019 ➔ Feb 2020; Trial primary completion date: Sep 2019 ➔ Dec 2019

Clinical • Trial completion date • Trial primary completion date

Cortico-Amygdala-Striatal Activation by Modafinil/Flecainide Combination. (PubMed, Int J Neuropsychopharmacol) - "These regions, highly involved in the regulation of sleep-wake cycle, emotions, and cognitive functions were hence quantitatively modulated by THN102. Data presented here provide the first evidence of a regional brain activation induced by THN102, currently being tested in a phase II clinical trial in narcoleptic patients."

Journal

Safety and Efficacy of THN102 on Sleepiness in Narcoleptic Patients (clinicaltrials.gov) - P2; N=51; Completed; Sponsor: Theranexus; Recruiting ➔ Completed

Clinical • Trial completion

Safety and Efficacy of THN102 in Patients With Parkinson's Disease and Excessive Daytime Sleepiness (clinicaltrials.gov) - P2; N=60; Recruiting; Sponsor: Theranexus; Trial primary completion date: Mar 2019 ➔ Sep 2019

Clinical • Trial primary completion date