Biotie Therapies

Biotie Therapies was a Finnish biotechnology and pharmaceutical company headquartered in Turku. Its research and development portfolio concentrated on disorders of the central nervous system and on selected inflammatory and fibrotic diseases. Areas pursued by the company included Parkinson’s disease, Alzheimer’s disease and other cognitive disorders, alcohol dependence, cocaine dependence, post-traumatic stress disorder, chronic obstructive pulmonary disease, rheumatoid arthritis, and inflammatory or fibrotic liver disease. The business was built through a series of corporate combinations. Biotie Therapies Corp. was incorporated in 1998, and in 2002 it was combined with Oy Contral Pharma Ltd and Carbion Inc. to form the broader Biotie Therapies group. The company subsequently expanded its discovery and development capabilities through the acquisition of German pharmaceutical discovery company Elbion GmbH in 2008 and pharmaceutical company Synosia Therapeutics in 2011. In 2010, Biotie transferred its preclinical assets into biocrea GmbH and retained a minority interest in that company, changing the structure of its early-stage research activities. Biotie operated primarily as a research-driven biopharmaceutical developer rather than as a large-scale commercial pharmaceutical manufacturer. It relied on licensing, development, and commercialization partnerships, including agreements with H. Lundbeck A/S and UCB. Its most advanced commercial program was nalmefene, marketed in Europe as Selincro. H. Lundbeck received European Commission marketing authorization for the product in February 2013. Selincro was designed for alcohol-dependent adults who required a reduction in alcohol consumption and used an as-needed dosing approach rather than continuous administration. Another major program was tozadenant, also known as SYN115, an orally administered selective adenosine A2A receptor antagonist investigated for Parkinson’s disease and other central nervous system indications. Biotie also developed or investigated nepicastat, a dopamine beta-hydroxylase inhibitor for cocaine dependence and post-traumatic stress disorder; a VAP-1 monoclonal antibody for inflammatory diseases; and ronomilast, a PDE4 inhibitor intended for chronic inflammatory respiratory disorders including chronic obstructive pulmonary disease. Acorda Therapeutics acquired Biotie in January 2016 in a transaction valued at approximately US$363 million. The acquisition ended Biotie’s independent existence as a listed Finnish company and transferred its development portfolio to Acorda. Tozadenant was later discontinued in 2017 after deaths and severe adverse events, including agranulocytosis, occurred during a Phase III study. Biotie is therefore best understood historically as an acquired Finnish biotechnology company whose principal legacy lies in addiction medicine, central-nervous-system drug discovery, and the development of Selincro.

Biotie Therapies emerged from Finland’s biotechnology sector as a company focused on translating pharmaceutical research into treatments for diseases with substantial unmet medical need. Biotie Therapies Corp. was incorporated in 1998. In 2002, it was formed into a broader operating group through the merger of Biotie Therapies Corp., Oy Contral Pharma Ltd, and Carbion Inc. This combination gave the company a wider platform for drug discovery and clinical development. The company’s scientific focus centered on the nervous system and on disorders in which conventional treatment options were limited or poorly tolerated. Its research areas included Parkinson’s disease, Alzheimer’s disease and other cognitive disorders, alcohol dependence, cocaine dependence, and post-traumatic stress disorder. Biotie also explored inflammatory and fibrotic liver disease and other chronic inflammatory conditions. Rather than operating as a diversified consumer pharmaceutical business, it functioned mainly as a development-stage biotechnology company whose value depended on clinical progress, regulatory milestones, intellectual property, and partnerships. Biotie expanded its capabilities through acquisitions. In 2008, it acquired Elbion GmbH, a German pharmaceutical discovery and development company based in Radebeul. The transaction strengthened Biotie’s research infrastructure and added discovery expertise. In 2010, Biotie transferred all of its preclinical assets into biocrea GmbH and became a minority shareholder. This restructuring separated early preclinical activities from Biotie’s principal development organization and allowed the company to concentrate more directly on clinical and later-stage programs. In 2011, Biotie acquired Synosia Therapeutics, adding a portfolio of central nervous system and addiction-related programs. Several of the resulting candidates were identified by Synosia development codes, including SYN115, later known as tozadenant, and SYN117, later known as nepicastat. Biotie also maintained development and commercialization relationships with established pharmaceutical companies, notably H. Lundbeck A/S and UCB. The company’s most important commercial achievement was nalmefene. Developed for alcohol dependence and later marketed in Europe under the name Selincro, nalmefene was intended for patients who needed to reduce alcohol consumption. Unlike therapies designed to enforce complete abstinence or medicines taken continuously, Selincro was positioned as an as-needed tablet used when the patient perceived a risk of drinking. Clinical findings cited for the program indicated reductions in average alcohol intake and in the number of heavy-drinking days. H. Lundbeck obtained European Commission marketing authorization on 28 February 2013 and prepared launches in European markets. Biotie’s other programs remained at different stages of clinical or preclinical development. Tozadenant was an orally administered, selective adenosine A2A receptor antagonist investigated for Parkinson’s disease and other central nervous system disorders. Nepicastat was designed to inhibit dopamine beta-hydroxylase and was investigated for cocaine dependence and post-traumatic stress disorder. A VAP-1 monoclonal antibody entered early clinical investigation for inflammatory diseases, including rheumatoid arthritis, based on the possibility that blocking vascular adhesion protein-1 could reduce the movement of leukocytes into inflamed tissue. Ronomilast, a PDE4 inhibitor, was pursued for chronic inflammatory respiratory disease and chronic obstructive pulmonary disease. In January 2016, Acorda Therapeutics acquired Biotie for approximately US$363 million. The transaction ended Biotie’s independent corporate and stock-market identity and gave Acorda control of its pipeline and commercial interests. The later history of tozadenant demonstrated the risks inherent in the portfolio: in 2017, development was discontinued after five deaths and severe adverse events, including agranulocytosis, were reported in a Phase III study and considered possibly associated with the drug. Biotie’s historical contribution is consequently associated both with the European commercialization of Selincro and with a broad but uneven pipeline spanning addiction medicine, neurology, psychiatry, immunology, and respiratory disease.

1. 2017Tozadenant program discontinued

   Development of tozadenant was stopped after deaths and severe adverse events were reported in its Phase III program.

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2. 2016Acquisition by Acorda Therapeutics

   Acorda Therapeutics acquired Biotie for approximately US$363 million, ending Biotie’s independent corporate status.

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3. 2013European authorization of Selincro

   The European Commission granted marketing authorization for nalmefene, marketed as Selincro, with H. Lundbeck as commercialization partner.

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4. 2011Acquisition of Synosia Therapeutics

   Biotie acquired Synosia Therapeutics, adding drug-development programs and central nervous system research capabilities.

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5. 2010Preclinical assets transferred to biocrea

   Biotie transferred its preclinical assets into biocrea GmbH and retained a minority interest.

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6. 2008Acquisition of Elbion GmbH

   Biotie acquired German pharmaceutical discovery and development company Elbion GmbH in Radebeul.

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7. 2002Merger creates the broader Biotie Therapies group

   Biotie Therapies Corp. merged with Oy Contral Pharma Ltd and Carbion Inc.

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8. 1998Biotie Therapies Corp. incorporated

   Biotie Therapies Corp. was incorporated in Finland as the foundation of the later Biotie Therapies group.

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A research-focused biopharmaceutical developer specializing in neurological, psychiatric, addiction-related, inflammatory, and fibrotic disease programs, with commercialization pursued through pharmaceutical partnerships.

• Selincro (nalmefene)Alcohol-dependence medicine2013

  Selincro was Biotie’s most advanced and commercially significant medicine. Nalmefene was developed for alcohol-dependent adults seeking to reduce alcohol consumption. Its distinguishing treatment concept was as-needed use, allowing patients to take the tablet when they anticipated a risk of drinking rather than relying exclusively on continuous daily dosing. H. Lundbeck partnered with Biotie and received European Commission marketing authorization on 28 February 2013. The product was prepared for launch in European markets during 2013.

• Tozadenant (SYN115)Neurology drug candidate

  Tozadenant was an orally administered, selective antagonist of the adenosine A2A receptor. Biotie pursued it as a potential treatment for Parkinson’s disease and other central nervous system disorders. The program advanced to Phase III under Acorda’s ownership, but development was discontinued in 2017 after five patient deaths and severe adverse events, including agranulocytosis, were reported and considered possibly related to treatment.

• Nepicastat (SYN117)Addiction and psychiatric drug candidate

  Nepicastat was an orally administered, selective inhibitor of dopamine beta-hydroxylase. The mechanism was investigated for cocaine dependence and post-traumatic stress disorder. The program formed part of Biotie’s broader strategy of applying central nervous system pharmacology to addiction and psychiatric conditions for which effective medicines were limited.

• VAP-1 monoclonal antibodyInflammation biologic

  Biotie investigated a monoclonal antibody directed at vascular adhesion protein-1, or VAP-1. The therapeutic concept was to reduce inflammatory leukocyte migration into affected tissues. The program entered Phase I testing in patients with rheumatoid arthritis and was also relevant to other autoimmune or inflammatory diseases, including ulcerative colitis and psoriasis.

• RonomilastRespiratory anti-inflammatory drug candidate

  Ronomilast was a small-molecule phosphodiesterase-4 inhibitor developed for chronic inflammatory disorders, particularly chronic obstructive pulmonary disease. Preclinical and early clinical findings were described as supporting a potentially acceptable safety profile. Biotie was planning a Phase II COPD study and seeking a partner for later-stage development.

• 2017Stop tozadenant developmentOther

  Five deaths and severe adverse events, including agranulocytosis, occurred during the tozadenant Phase III program.

  What changed. Acorda discontinued development of the agent in November 2017.

  Aftermath. The discontinuation removed one of the principal inherited Parkinson’s disease programs from the post-acquisition pipeline.

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• 2016Acorda Therapeutics acquisitionM&A

  Acorda sought to acquire Biotie and obtain its marketed and clinical-stage central nervous system portfolio.

  What changed. Acorda acquired Biotie Therapies in January 2016.

  Aftermath. Biotie ceased to operate as an independent listed Finnish biopharmaceutical company and became part of Acorda’s business.

  Acquisition value. US$363 million (January 2016)

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• 2013Advance Selincro toward European commercializationProduct launch

  The European Commission granted marketing authorization for nalmefene for the reduction of alcohol consumption in alcohol-dependent adults.

  What changed. H. Lundbeck prepared to launch Selincro in initial European markets as Biotie’s commercialization partner.

  Aftermath. Selincro became Biotie’s principal authorized product and its most visible commercial achievement.

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• 2010Separate preclinical assets into biocreaStrategy

  Biotie reorganized its research activities by transferring all preclinical assets into biocrea GmbH.

  What changed. The assets were placed in a new company in which Biotie retained a minority shareholding.

  Aftermath. The restructuring enabled Biotie to focus more directly on clinical and development-stage programs while maintaining an interest in the preclinical portfolio.

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• 2017Tozadenant development discontinued after Phase III safety concerns

  Acorda announced discontinuation of tozadenant after five patients in the Phase III program died and other severe adverse events, including agranulocytosis, were considered possibly related to treatment.

  OtherRegulation
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• 2016Acorda Therapeutics acquires Biotie Therapies

  Acorda Therapeutics acquired Biotie Therapies in January 2016 for approximately US$363 million, bringing Biotie’s drug-development portfolio under Acorda’s ownership.

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• 2013Biotie receives European marketing authorization for Selincro

  The European Commission authorized nalmefene, marketed as Selincro, for the reduction of alcohol consumption in alcohol-dependent adults. H. Lundbeck was Biotie’s commercialization partner for the product.

  Product launchRegulation
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1. Biotie Therapies