Revive Therapeutics Ltd. Announces Initiation of A Phase 2a Study of REV-001 (Tianeptine) for the Prevention of Opioid-Induced Respiratory Depression

TORONTO, ONTARIO--(Marketwired - Jan. 15, 2014) - Revive Therapeutics Ltd. (TSXV:RVV) ("Revive") announced today that the initiation of a Phase 2a proof of concept study of REV-001 (tianeptine), for the prevention of opioid-induced respiratory depression, is well underway. The study is being conducted at the Leiden University Medical Center in The Netherlands under the supervision of Prof. Dr. Albert Dahan, M.D., Ph.D.

The Phase 2a proof-of-concept study of REV-001 is a placebo-controlled, double-blind, randomized two-way crossover study in healthy adult subjects. The study is designed to evaluate the effect of an oral dose of tianeptine on alfentanil-induced respiratory depression and antinociception. The study will be performed in 16 healthy male and female volunteers in the age group of 18-35 years. Each subject will be tested twice, once during the infusion of alfentanil following placebo, and once during the infusion of alfentanil following an oral dose of tianeptine. The first cohort (8 subjects) will receive 37.5 mg tianeptine and the second cohort (8 subjects) will receive either 25 mg or 50 mg. An analysis of the first cohort will be performed to assess the magnitude of effect. If the reversal effect in the first cohort is greater than 75% (in terms of increase in slope of the ventilator response to CO₂ during alfentanil infusion relative to baseline values) the second cohort will be treated with an oral dose of 25 mg tianeptine; if the reversal is less than 75% the second cohort will be treated with an oral dose of 50 mg tianeptine.

"We are pleased that the initiation of the first cohort of 8 subjects has occurred, marking an important milestone for Revive," said Fabio Chianelli, Revive's Chief Executive Officer. "We aim to position REV-001 as a novel therapy for the prevention of post-operative opioid-induced respiratory depression in patients with sleep apnea."

About REV-001 (Tianeptine)

REV-001 is the repurposing of the drug tianeptine, an old but unique anti-depressant drug, which is marketed in Asia, parts of Europe (e.g. France) and South America. Despite its narrow geographic scope, the decades-long clinical experience of tianeptine suggests much about its safety. In fact, tianeptine has been shown to have substantial cardiovascular and other safety at both normal doses and in overdose. (Source: Wilde, M. I. & Benfield, P. Drugs 49, 411-439 (1995)). More recently, tianeptine was shown for the first time to prevent opioid(morphine)- induced respiratory depression in an animal model. The novel findings in the study enabled Revive to apply for intellectual property protection covering the use of tianeptine to treat respiratory depression.

About Sleep Apnea and Opioid-induced respiratory depression

According to the Centers for Disease Control and Prevention, approximately 70 million people in the United States are affected by sleep disorders, such as obstructive sleep apnea ("OSA"). The risk of perioperative complications increase substantially with those who have OSA. With 51.4 million inpatient surgical procedures performed annually (2010) in the U.S. (Source: http://www.cdc.gov/nchs/fastats/insurg.htm), hospitals must take into consideration the financial implications that may become prevalent for patients who have OSA in order to reduce the risk of adverse events, such as opioid-induced respiratory depression. It has been estimated that between 29% and 41% are at high risk of opioid-induced respiratory depression. (Source: Hanna MH et al. Anesthesiology. 2005;102(4): 815-821 and Overdyk FK et al. Anesth Analg. 2007;105(2): 412-418). Currently, there are no approved drugs for OSA and the only drug treatments to counter opioid-induced respiratory depression is to administer opiate receptor antagonists such as naloxone (Narcan®). However, those antagonists eliminate the analgesic activity of the opioid drug and thus are rarely used by hospitals and healthcare facilities to prevent or treat opioid-induced respiratory depression. According to an article published in the New England Journal of Medicine in June 2013, perioperative sleep apnea in the United States has been considered as an 'Epidemic'.

About Revive Therapeutics Ltd.

Revive Therapeutics Ltd. is a Canadian public company (TSX VENTURE:RVV) focused on acquiring, developing and commercializing treatments for major market opportunities such as sleep apnea, gout and rare diseases. Revive aims to bring drugs to market by finding new uses for old drugs, also known as drug repurposing, and improving the therapeutic performance of existing drugs for underserved medical needs. Additional information on Revive is available at www.revivethera.com.

The information in this news release includes certain information and statements about management's view of future events, expectations, plans and prospects that constitute forward looking statements that may not be based on historical fact, including without limitation statements containing the words "believe", "may", "plan", "will", "estimate", "continue", "anticipate", "intend", "expect" and similar expressions. These statements are based upon assumptions that are subject to significant risks and uncertainties. Because of these risks and uncertainties and as a result of a variety of factors, the actual results, expectations, achievements or performance may differ materially from those anticipated and indicated by these forward looking statements. Such factors include, among others, Revive's stage of development, lack of any product revenues, additional capital requirements, risk associated with the completion of clinical trials and obtaining regulatory approval to market products, the ability to protect intellectual property, dependence on business partners and the prospects for negotiating joint ventures, distribution and licensing arrangements and their timing.
Specifically, certain risks and uncertainties that could cause such actual events or results expressed or implied by such forward-looking statements and information to differ materially from any future events or results expressed or implied by such statements and information include, but are not limited to; the risks and uncertainties that Revive may not be able to successfully develop and obtain regulatory approval for its products; intellectual property disputes; future operating results are uncertain and likely to fluctuate; ability to raise additional capital; successfully establishing additional corporate collaborations, distribution or licensing arrangements; establishing marketing and the costs of launching products may be restricting; Revive's lack of experience in commercial manufacturing; increased competition from pharmaceutical and biotechnology companies; and other factors as described in detail in Revive's filings on SEDAR (www.sedar.com), including, without limitation, Revive's Filing Statement dated November 26, 2013 filed on SEDAR on November 27, 2013. Given these risks and uncertainties, readers are cautioned not to place undue reliance on such forward-looking statements and information, which are qualified in their entirety by this cautionary statement. Although Revive believes that the expectations reflected in forward looking statements are reasonable, it can give no assurances that the expectations of any forward looking statements will prove to be correct. Except as required by law, Revive disclaims any intention and assumes no obligation to update or revise any forward looking statements to reflect actual results, whether as a result of new information, future events, changes in assumptions, changes in factors affecting such forward looking statements or otherwise.

Neither 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 release.