San Diego, California – May 18, 2022 (Newsfile Corp.) (Investorideas.com Newswire) Thiogenesis Therapeutics, Corp. (TSXV: TTI) (“Thiogenesis” or the “Company”) a clinical-stage biotechnology company developing sulfur-containing therapeutics for serious pediatric diseases, today announces positive results from its Phase 1 clinical study of oral TTI-0102 in healthy volunteers in Australia.
The Phase 1, “Open-Label, Dose-Escalation Study – to Evaluate Safety, Tolerability and Pharmacokinetics of Oral TTI-0102 Compared to Cystagon(R) (cysteamine bitartrate) in Healthy Volunteers,” demonstrated that TTI-0102, which acts as a precursor to the thiol-active compound cysteamine, was safe and well tolerated at dose levels ranging from 600 mg cysteamine-base equivalent to 2400 mg cysteamine-base equivalent with no serious adverse events. The pharmacokinetic (PK) profile suggests the potential for once-a-day dosing at target therapeutic levels compared to four times a day dosing with Cystagon(R).
The results from this study will be used to support Thiogenesis’ Investigational Medicinal Product Dossier (IMPD) submission in Europe and its Investigational New Drug (IND) submissions in the US for human efficacy trials in multiple disease indications.
“We are very encouraged with the results of our Phase 1 study exhibiting no serious adverse events for TTI-0102, even at the maximum dosage,” said Patrice Rioux, M.D., Thiogenesis’ Founder and Chief Executive Officer. “Cysteamine has been studied as a compound with significant promise in a number of indications over several decades, however, its development has been constrained due to its dose-limiting side effects, most notably nausea.”
Dr. Rioux continued, “These PK results demonstrate that TTI-0102 can significantly increase dosing and achieve a higher blood level “area under the curve” (AUC) of the active compound, without increasing its peak concentration or Cmax. The peak Cmax of cysteamine is typically correlated with the timing of its debilitating side effects. With this promising PK data, we intend to submit for regulatory clearance to initiate human efficacy trials with TTI-0102 in mitochondrial disease and Rett’s syndrome.”
Summary of TTI-0102 Phase 1 Clinical Trial Data
The Phase 1 study enrolled 12 healthy volunteers that were dosed with 600 mg of Cystagon(R) as a control and patients were later given one of: 600 mg cysteamine-base equivalent; 1200 mg cysteamine-base equivalent; or 2400 mg cysteamine-base equivalent of TTI-0102.
As expected, the most common Treatment Emergent Adverse Effects (TEAEs) reported following the administration of 600 mg of Cystagon(R) was nausea. Following TTI-0102 administration, no nausea was reported, and the only moderately graded TEAE reported was abnormal skin odor in 3 participants in the 2400 mg cysteamine-base equivalent group.
The target therapeutic levels of cysteamine for TTI-0102 in the 1200 mg cysteamine-base equivalent group was maintained for over 12 hours, therefore TTI-0102’s PK data supports dosing twice-a-day and potentially once a day, depending on the indication.
The Cmax of cysteamine with dosing of 600 mg of Cystagon(R) was 3.19 ? 1.12 mg/mL compared to 3.49 ? 0.95 mg/mL with dosing of 2400 mg cysteamine-base equivalent of TTI-0102. The difference was not statistically significant (p=0.61) even at the maximum dose of TTI-0102. These results support the ability to administer a higher dose level of TTI-0102 without risking a higher Cmax of cysteamine that is associated with side effects.
The AUC for the dosing of 600 mg of Cystagon(R) was 7.32 ? 1.76 hr.mg/mL compared to 20.38 ? 4.27 hr.mg/mL for the 2400 mg cysteamine-base equivalent in the TTI-0102 group. The increase in the AUC was statistically significant, representing an increase of 278% (p<0.01).
The higher blood level AUC achieved without increasing the Cmax results in an increase in the availability of TTI-0102 to tissue over time, again without an increase in the side effects associated with increased dosing of cysteamine.
Thiogenesis’ lead compound, TTI-0102, is an asymmetric disulfide that acts as a precursor to the thiol-active compound cysteamine; it also has additional therapeutic properties that may provide therapeutic advantages over cysteamine. Importantly, TTI-0102 is a new chemical entity (NCE), with an initial US patent granted in November 2021 and additional US and international patents pending. Thiols are versatile bio-active molecules that are known to be involved in a number of chemical reactions and metabolic processes making them exciting candidates for a number of therapeutic applications.
As an asymmetric disulfide, TTI-0102 consists of two different thiol molecules that have been synthesized into a single compound; the molecules are cysteamine and pantetheine (both contain an active functional R-SH group where the S represents sulfur). TTI-0102 transforms into two active cysteamine molecules in two different steps:
First, TTI-0102 is taken orally and as TTI-0102 passes through the gastrointestinal tube it interacts with other thiols, this causes the initial cysteamine molecule to be released.
Second, the remaining pantetheine molecule moves along to the small intestine, where it comes into contact with certain enzymes (Vanin-1) that hydrolyze it into another cysteamine molecule and pantothenic acid (Vitamin B5).
This two-stage process occurs over a period of several hours, it is this process that caps the Cmax of cysteamine, extends the duration of the therapeutic levels of TTI-0102 and expands the AUC.
Historically, cysteamine was studied as far back as the 1950’s to protect against radiation poisoning. It has also been studied for other diseases including: paracetamol poisoning, lupus, copper chelation, Huntington’s disease and non-alcoholic fatty liver disease (NASH) among others. The only indication for which cysteamine has been approved is cystinosis, an ultra-orphan lysosomal storage disease resulting from a build-up of cystine in cells, which is toxic. Cystagon(R) (immediate release cysteamine bitartrate) approved to treat cystinosis in 1994 and Procysbi(R) (enterically coated, delayed release cysteamine bitartrate) approved to treat nephropathic cystinosis in 2013, act as cystine depleting drugs. The inability to administer cysteamine at optimal therapeutic doses without side effects has limited its therapeutic development. TTI-0102 was developed to potentially overcome this limitation.
Thiogenesis Therapeutics, Corp. (TSXV: TTI), a clinical-stage biopharmaceutical company operating through its wholly subsidiary based in San Diego, CA, is publicly traded on the TSX Venture Exchange. Thiogenesis is developing sulfur-containing therapeutics that are thiol-active compounds, to potentially treat serious pediatric diseases with unmet clinical needs. The Company’s leadership team has extensive knowledge and expertise in drug development, having taken multiple pediatric and orphan drugs through clinical trials, regulatory approval and successful commercial launch at Raptor Pharmaceuticals, (formerly Nasdaq: RPTP) and BioMarin Pharmaceutical. (Nasdaq: BMRN). The Company’s initial target indications include Mitochondrial Encephalopathy Lactic Acidosis and Stroke (MELAS) and Rett’s syndrome.
For further information, please contact:
Brook Riggins, Director and CFO
Tel.: +420 776 659 259
This news release contains certain forward-looking statements and forward-looking information (collectively referred to herein as “forward-looking statements”) within the meaning of Canadian securities laws including, without limitation, statements with respect to the future investments by the Company. All statements other than statements of historical fact are forward-looking statements. Undue reliance should not be placed on forward-looking statements, which are inherently uncertain, are based on estimates and assumptions, and are subject to known and unknown risks and uncertainties (both general and specific) that contribute to the possibility that the future events or circumstances contemplated by the forward-looking statements will not occur. Although the Company believes that the expectations reflected in the forward-looking statements contained in this press release, and the assumptions on which such forward-looking statements are made, are reasonable, there can be no assurance that such expectations will prove to be correct. Readers are cautioned not to place undue reliance on forward-looking statements included in this document, as there can be no assurance that the plans, intentions or expectations upon which the forward-looking statements are based will occur. By their nature, forward-looking statements involve numerous assumptions, known and unknown risks and uncertainties that contribute to the possibility that the predictions, forecasts, projections and other forward-looking statements will not occur, which may cause the Company’s actual performance and results in future periods to differ materially from any estimates or projections of future performance or results expressed or implied by such forward-looking statements. The forward-looking statements contained in this news release are made as of the date hereof and the Company does not undertake any obligation to update publicly or to revise any of the included forward-looking statements, except as required by applicable law. The forward-looking statements contained herein are expressly qualified by this cautionary statement.
Neither the TSX Venture Exchange nor its Regulation Services Provider (as that term is defined in the policies of the TSX Venture Exchange) accepts responsibility for the adequacy or accuracy of this news release.
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