Company: ACHV
Filing Date: 2025-03-11
Form Type: 10-K
Source: 0000950170-25-036831
Chunk: 12

Company: ACHIEVE LIFE SCIENCES, INC.
Filing Date: 2025-03-11
Form: 10-K
Item: Item 1
Chunk 12
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 which we expect to complete approximately 12 months after initiation, and may explore additional indications for the treatment of nicotine dependence in the future. 

Cytisinicline as our Product Candidate

Our product candidate, cytisinicline, is a naturally occurring, plant-based alkaloid. In 2018, the U.S. Adopted Names Council adopted cytisinicline as the non-proprietary, or generic, name for the substance also known as cytisine.

Cytisinicline is structurally similar to nicotine and has a well-defined, dual-acting mechanism of action, being both a receptor agonist and antagonist. It is believed to work in treating nicotine dependence for smoking and e-cigarette cessation by interacting with nicotine receptors in the brain by reducing the severity of withdrawal symptoms, and reducing the reward and satisfaction associated with nicotine products. Cytisinicline is an investigational product candidate being developed for treatment of nicotine dependence and has not been approved by the FDA for any indication in the United States.

Cytisinicline as a 25-day downward titration regimen is an established smoking cessation treatment that has been approved and marketed in Central and Eastern Europe by Sopharma AD, or Sopharma, for over 20 years. It is estimated that over 20 million people have used Sopharma’s cytisinicline product to help treat nicotine dependence. We have developed an improved dosage, formulation, and simpler treatment schedule. The administration of our cytisinicline has demonstrated robust efficacy with minimal levels of adverse events in two randomized placebo-controlled Phase 3 studies. We have an exclusive license and a supply agreement with Sopharma for the development and commercialization of cytisinicline outside of Sopharma’s territories, which are predominately located in Central and Eastern Europe.

Cytisinicline Mechanism of Action

Cytisinicline binds with high affinity to the alpha-4 beta-2, or α4β2, nicotinic acetylcholine receptors in the brain. The α4β2 nicotinic receptor is a well-understood target in dependence. When nicotine binds to this receptor, it causes dopamine to be released in the mid-brain, reinforcing the dopamine reward system. This receptor has been implicated in the development and maintenance of nicotine dependence. Cytisinicline is believed to act as a partial agonist/antagonist binding to α4β2 nicotinic receptors in the brain and is thought to have two potential consequences in treating nicotine dependence. First, the partial agon