DUBLIN – Addex Pharmaceuticals Ltd.'s wilderness years are over.

The company began 2018 with a licensing and collaboration deal in addiction with Indivior plc worth up to $339 million. The agreement is focused on ADX-71441, a positive allosteric modulator (PAM) of the gamma-aminobutyric acid (GABA) B (GABAB) receptor, which is currently in late preclinical development. Addex is getting just $5 million of the total up front and another $4 million in research funding over the next two years, with the rest to come in development, regulatory and commercial milestones. It would also receive tiered royalties on product sales.

For Addex, the deal has a significance that extends beyond the specific details of the agreement. It marks the company's return to the dealmaking fray after an extended absence during which it flirted heavily with oblivion.

"There was never anything wrong with the platform," Tim Dyer, CEO of Geneva-based Addex told BioWorld. "Addex was basically destroyed by a very poor financial strategy."

The company had pursued deals without raising sufficient cash in parallel. When the deals didn't materialize – and when, as is routine in biotech, several clinical programs failed to deliver – it faced extinction. "As a public company it's extremely difficult to come back from the dead," Dyer said.

But that's what it has achieved – just about. Noncommercial research collaborations with academic scientists, patient groups including the Michael J. Fox Foundation, and governmental research bodies including the U.S. National Institute of Drug Abuse and the National Institute on Alcohol Abuse and Alcoholism, helped to keep the company ticking over and generating data to support its drug development programs. That work contributed to the company's ability to land the deal with London-based Indivior, a company which has its roots in the buprenorphine business group of Reckitt Benckiser Group plc, of Slough, U.K.

"The platform is really back up and running, more or less at full steam," Dyer said. It comprises a set of biological as well as chemical assets, including about 100 assays for the functional characterization of positive and negative allosteric modulators of drug targets.

ADX-71441 has a similar mechanism to baclofen, a generic GABAB receptor agonist widely used to treat spasticity in movement-related disorders and alcohol addiction. Baclofen has a temporary authorization in France in the latter indication. It has a narrow therapeutic index, however, because of a range of side effects, including convulsions, hallucinations, mood changes and blurred or double vision.

"We expect to have less side effects. The use of baclofen is really hampered by side effects," Robert Lütjens, head of discovery at Addex, told BioWorld.

ADX-71441 is nearing the completion of preclinical toxicity studies, after which Indivior will file for an IND. "We're expecting it to go into man in the second half of 2018," Lütjens said.

Although the immediate cash influx from the Indivior deal is modest, it offers Addex a valuable lifeline. Its immediate cash needs, moreover, are not large. "We've been running the company on about $2 million a year for the last four years," Dyer said. "The $5 million from Indivior, which in this industry seems like peanuts, together with our year-end cash balance, gives us funding into 2021."

Its ambitions extend well beyond marking time with the progress of ADX-71441, however. It also aims to move its lead compound, dipraglurant, a negative allosteric modulator of the metabotropic glutamate receptor 5 (mGluR5), into a registration trial in levodopa-induced dyskinesia (LID) associated with Parkinson's disease (PD) – and into a clinical proof-of-concept trial in dystonia as well. And it aims to do so before year-end.

"That is a stretch goal," Dyer admitted. The company would need to raise additional cash to attain either objective – a share issue or a partnering deal are the obvious options here.

The company has taken heart from the recent FDA approval in the same indication of Gocovri (amantadine extended-release capsules), which San Diego-based Adamas Pharmaceuticals Inc. developed. Dipraglurant  acts on the same pathway and has demonstrated superior activity in preclinical research. (See BioWorld, Aug. 28, 2017.)

Shares in Addex (Zurich:ADXN) peaked at CHF3.05, a one-year high, during trading Wednesday before closing at CHF3.04, a gain of almost 33 percent on its previous close of CHF2.29.