Addex, Indivior Forge $335M Addiction Disorder Tie-Up

SLOUGH, England and RICHMOND, Va., Jan. 3, 2018 /PRNewswire/ --Indivior today announced that Indivior UK Limited has entered into a strategic collaboration with Addex Pharma S.A., a wholly-owned subsidiary of Addex Therapeutics (SIX: ADXN) (“Addex”), in the field of GABA_B positive allosteric modulators (PAMs). GABA_B PAMs have demonstrated preclinical efficacy and tolerability in animal models for alcohol use disorder (AUD) and cocaine use disorder (CUD)^1,2. The collaboration includes an exclusive global license to lead candidate ADX71441, which is a novel, first-in-class, oral, small molecule and is expected to enter Phase 1 trials in 2018. The collaboration also includes exclusive global license to backup GABA_B PAM compounds, as well as a research collaboration focused on discovering additional GABA_B PAMs. The Addex GABA_B program was recently awarded a $5.3 million grant by the National Institute on Drug Abuse (“NIDA”) to support the development of ADX71441 in CUD³.

Under the terms of the agreement, Indivior is making an upfront payment to Addex of $5 million, and will also invest in research funding over the next two years to discover additional GABA_B PAM compounds commercially-viable to treat addiction. Potential milestone payments to Addex could total $330 million over time if all development, regulatory and sales goals are achieved.

“As part of our leadership position in addiction, among the key priorities we are pursuing is continuing to review and invest in promising new treatments for this chronic and relapsing disease,” said Shaun Thaxter, CEO of Indivior. “Modulation of the GABA_B receptor pathway is an attractive mechanism, particularly for the potential it holds in advancing treatments for AUD and CUD. Further, we are excited about this new strategic collaboration with Addex to discover additional compounds targeting the GABA_B receptor pathway, which will complement the current pipeline efforts we have underway to develop novel treatments for addiction.”

“We believe Addex has the most advanced science in the area of GABA_B allosteric modulation and look forward to rapidly advancing lead compound, ADX71441, into Phase 1 trials,” said Christian Heidbreder, Chief Scientific Officer of Indivior. “As we continue to collaborate with the Addex team, we believe there is great potential for additional compounds to be discovered and developed related to this important mechanism for addiction science.”

Addex’s GABA_B PAMs Program Focused on Addiction
Long-term exposure to drugs of abuse causes adaptive changes in several neurotransmitter systems, including gamma-aminobutyric acid (GABA) receptors. Research has shown that exposure to psychostimulants depresses the normal function of the GABA_B receptor signaling in the mesolimbic dopaminergic system⁴, which plays a role in the positive reinforcing properties of several drugs of abuse and may also contribute to the negative reinforcing effects associated with their withdrawal⁵. Therefore, full agonists aimed at the orthosteric site on the GABA_B receptor have been the target for the development of pharmacotherapies for AUD and CUD².

The efficacy of these full agonists at the orthosteric site on the GABA_B receptor, however, are limited due to tolerance and undesired side effects, including sedation, myorelaxing activity and hypothermia. Unlike orthosteric agonists, positive allosteric modulators (PAMs) work by only enhancing the activity of GABA_B receptors when and where needed physiologically. As such, GABA_B PAMs are expected to have significantly less undesired side effects than full GABA_B receptor agonists and to be suitable for long-term treatment without challenges related to tolerance⁶.

About Indivior
Indivior is a global specialty pharmaceutical company with a 20-year legacy of leadership in patient advocacy and health policy while providing education on evidence-based treatment models that have revolutionized modern addiction treatment. The name is the fusion of the words individual and endeavour, and the tagline “Focus on you” makes the Company’s commitment clear. Indivior is dedicated to transforming addiction from a global human crisis to a recognized and treated chronic disease. Building on its global portfolio of opioid dependence treatments, Indivior has a strong pipeline of product candidates designed to both expand on its heritage in this category and address other chronic conditions and co-occurring disorders of addiction, including AUD and schizophrenia. Headquartered in the United States in Richmond, VA, Indivior employs more than 900 individuals globally and its portfolio of products is available in over 40 countries worldwide. Visit www.indivior.com to learn more.

Forward-Looking Statements
This press release contains certain statements that are forward-looking and which should be considered, amongst other statutory provisions, in light of the safe harbour provisions of the United States Private Securities Litigation Reform Act of 1995. By their nature, forward-looking statements involve risk and uncertainty as they relate to events or circumstances that will or may occur in the future. Actual results may differ materially from those expressed or implied in such statements because they relate to future events. Forward-looking statements include, among other things, statements regarding our financial guidance for 2017 and our medium- and long-term growth outlook, our operational goals, our product development pipeline and statements regarding ongoing litigation.

Various factors may cause differences between Indivior’s expectations and actual results, including: factors affecting sales of Indivior Group’s products; the outcome of research and development activities; decisions by regulatory authorities regarding the Indivior Group’s drug applications; the speed with which regulatory authorizations, pricing approvals and product launches may be achieved; the outcome of post-approval clinical trials; competitive developments; difficulties or delays in manufacturing; the impact of existing and future legislation and regulatory provisions on product exclusivity; trends toward managed care and healthcare cost containment; legislation or regulatory action affecting pharmaceutical product pricing, reimbursement or access; claims and concerns that may arise regarding the safety or efficacy of the Indivior Group’s products and product candidates; risks related to legal proceedings; the Indivior Group’s ability to protect its patents and other intellectual property; the outcome of patent infringement litigation relating to Indivior Group’s products, including the ongoing ANDA lawsuits; changes in governmental laws and regulations; issues related to the outsourcing of certain operational and staff functions to third parties; uncertainties related to general economic, political, business, industry, regulatory and market conditions; and the impact of acquisitions, divestitures, restructurings, internal reorganizations, product recalls and withdrawals and other unusual items.

This press release does not constitute an offer to sell, or the solicitation of an offer to subscribe for or otherwise acquire or dispose of shares in the Company to any person in any jurisdiction to whom it is unlawful to make such offer or solicitation.

References

1. Hwa LS et al. 2014. Reduction of excessive alcohol drinking by a novel GABAB receptor positive allosteric modulator ADX71441 in mice. Psychopharmacology 231(2):333-43; Augier E et al. 2017. The GABAB Positive Allosteric Modulator ADX71441 Attenuates Alcohol Self-Administration and Relapse to Alcohol Seeking in Rats. Neuropsychopharmacology. 42(9):1789-1799.
2. Phillips & Reed 2014. Targeting GABAB receptors for anti-abuse drug discovery. Expert Opin Drug Discov. 9(11):1307-17.
3. https://www.addextherapeutics.com/en/news-and-events/press-releases/
4. Padgett CL et al. 2012. Methamphetamine-evoked depression of GABA(B) receptor signaling in GABA neurons of the VTA. Neuron 73, 978-989.
5. Wise RA 2004. Dopamine, learning and motivation. Nat Rev Neurosci 5:483-494
6. Filip et al. 2015. GABAB receptors as a therapeutic strategy in substance use disorders: focus on positive allosteric modulators. Neuropharmacology. 88:36-47.

View original content:http://www.prnewswire.com/news-releases/indivior-and-addex-enter-strategic-collaboration-to-accelerate-development-of-gabab-pams-for-addiction-disorder-treatments-300576742.html

SOURCE Indivior PLC