New scientific publications highlight the unique profile of Actelion's antimalarial compound

The antimalarial activity of ACT-451840 was studied in an experimental induced blood stage malaria clinical trial performed in collaboration with MMV Medicines for Malaria Ventures at the laboratories of Professor James McCarthy, MBBS, MD of the Royal Brisbane and Women's Hospital in Herston, Australia. In the trial, ACT-451840 was safe and well tolerated and showed clinical efficacy against the early stages of P. falciparum infections. The PK/PD model developed from this proof-of-concept study with eight healthy subjects enabled prediction of therapeutic effects, with cure rates following 1 week of therapy (single daily doses) predicted to be equivalent to artesunate monotherapy.

ABOUT MALARIA [6,7,8,9,10]
Malaria is one of the most important infectious diseases, threatening half of the world's population. In accordance to the latest estimates by the World Health Organization (WHO), in 2014, there were 198 million cases of this parasitic disease (infection with P. falciparum) with an estimated 584,000 deaths, out of the estimated 3.3 billion people at risk. 90% of the mortality was in sub-Saharan Africa, mostly among children under 5 years of age, attributing 78% of deaths. The WHO has declared malaria control a global development priority and has changed its recommendation from control programs to eradication programs. New drugs will be needed to make this possible.

The widespread resistance of P. falciparum to conventional monotherapies such as chloroquine, amodiaquine and sulfadoxine/pyrimethamine led to an urgent need for new therapies to combat increasing levels of resistance. The WHO currently recommends artemisinin-based combination therapy (ACT) as the first line therapy in areas with high prevalence of resistance. Even though artemisinins are the most potent and rapidly acting antimalarial agents available to date, they are associated with high recrudescence rates when used as monotherapy. However, worrying evidence of its decreasing efficacy is now widespread through Southeast Asia. Because of the concern for resistance development, new drugs with new mechanisms of action are needed. The development of these drugs requires fast and efficient processes.

REFERENCES

1. Christoph Boss, et al, Discovery and Characterization of ACT-451840: an Antimalarial Drug with a Novel Mechanism of Action, ChemMedChem 2016, 11, 1995 - 2014. DOI: 10.1002/cmdc.201600298
2. Amélie Le Bihan, et al. Characterization of Novel Antimalarial Compound ACT-451840: Preclinical Assessment of Activity and Dose-Efficacy Modeling, PLoS Medicine (2016): DOI:10.1371/journal.pmed.1002138.
3. Bruderer S, et al. 2015. First-in-humans study of the safety, tolerability, and pharmacokinetics of ACT-451840, a new chemical entity with antimalarial activity. Antimicrob Agents Chemother 59:935-942. DOI:10.1128/AAC.04125-14.
4. Andreas Krause, et al. Pharmacokinetic/pharmacodynamic modelling of the antimalarial effect of Actelion-451840 in an induced blood stage malaria study in healthy subjects, Br J Clin Pharmacol (2016) 82 412-421. DOI:10.1111/bcp.12962.
5. Ng CL, et al.,  CRISPR-Cas9-modified pfmdr1 protects Plasmodium falciparum asexual blood stages and gametocytes against a class of piperazine-containing compounds but potentiates artemisinin-based combination therapy partner drugs. Mol Microbiol. 2016 Aug; 101(3):381-93.
6. World Health Organization. World Malaria Report 2014, 2014.
7. The malERA Consultative Group on Drugs. A research agenda for malaria eradication: Drugs. PLoS Med 2011; 8: e1000402.
8. Roll Back Malaria Partnership. The global malaria action plan. 2008. http://www.rollbackmalaria.org/
9. Ashley EA,White NJ. Artemisinin-based combinations. Curr Opin Infect Dis 2005; 18: 531-6.
10. Ashley EA, et al. Spread of artemisinin resistance in Plasmodium falciparum malaria. N Engl J Med 2014; 371: 411-23.

Actelion Ltd.
Actelion Ltd. is a leading biopharmaceutical company focused on the discovery, development and commercialization of innovative drugs for diseases with significant unmet medical needs.

Actelion is a leader in the field of pulmonary arterial hypertension (PAH). Our portfolio of PAH treatments covers the spectrum of disease, from WHO Functional Class (FC) II through to FC IV, with oral, inhaled and intravenous medications. Although not available in all countries, Actelion has treatments approved by health authorities for a number of specialist diseases including Type 1 Gaucher disease, Niemann-Pick type C disease, Digital Ulcers in patients suffering from systemic sclerosis, and mycosis fungoides type cutaneous T-cell lymphoma.

Founded in late 1997, with now over 2,500 dedicated professionals covering all key markets around the world including Europe, the US, Japan, China, Russia and Mexico, Actelion has its corporate headquarters in Allschwil / Basel, Switzerland.

Actelion shares are traded on the SIX Swiss Exchange (ticker symbol: ATLN) as part of the Swiss blue-chip index SMI (Swiss Market Index SMI^®). All trademarks are legally protected by their respective owners.

For further information please contact:
Andrew Weiss
Senior Vice President, Head of Investor Relations & Corporate Communications
Actelion Pharmaceuticals Ltd, Gewerbestrasse 16, CH-4123 Allschwil
+41 61 565 62 62
www.actelion.com

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