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

Actelion Pharmaceuticals Ltd / New scientific publications highlight the unique profile of Actelion's antimalarial compound . Processed and transmitted by Nasdaq Corporate Solutions. The issuer is solely responsible for the content of this announcement.

ALLSCHWIL/BASEL, SWITZERLAND - 17 October 2016 - Actelion Ltd (SIX: ATLN) announced today that a series of recently published scientific articles [1,2,3,4,5]  describing the unique profile of the company's orally-active antimalarial compound, ACT-451840, has reinvigorated interest in the compound. Actelion is in discussions to find a partner with the expertise and resources to bring this promising therapy to patients.

ACT-451840 appears to have a distinct mode of action that sets it apart from current antimalarial drugs, including artemisinins. It has a rapid onset of action as well as activity on all blood-borne (erythrocytic) stages, which is retained against multiple resistant parasites, including artemisinin-resistant strains. Unlike the majority of antimalarial agents, ACT-451840 has the potential to block disease transmission due to its activity on gametocytes.

The discovery and characterization work for ACT-451840 was carried out in close collaboration with the Swiss Tropical and Public Health Institute (Swiss TPH). Initial clinical evaluation of ACT-451840 - 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 - showed good tolerability and confirmed the fast action and gametocidal activity.

The company believes that ACT-451840 could form the basis of novel combinations, which would have the potential to replace artemisinin-based combinations, as first evidence of resistance to artemisinin is appearing.

Martine Clozel, MD and Chief Scientific Officer, commented: "The results we have seen with Actelion's compound against the deadliest form of malaria, even when parasites have developed resistance against the current gold-standard therapies, have impressed many of our academic partners. On the back of the recently published preclinical and clinical data, we are in discussions to find a partner with experience in the development of this indication, in an attempt to help the World Health Organization meet their goal of eradicating malaria by 2030."

Martine Clozel concluded: "The growing signs of resistance of the malarial parasite to current antimalarial drugs further increase the urgent need for treatments with new mechanisms of action. Our long collaboration with outstanding partners such as the Swiss TPH has resulted in a compound with great potential, and I truly believe that the results we have seen warrant further investigation together with a partner to continue its development."

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ABOUT ACT-451840 [1,2,3,4,5]
ACT-451840 was discovered in a drug discovery project at Actelion in close collaboration with the Swiss Tropical and Public Health Institute (Swiss TPH). In preclinical studies, the chemical compound ACT-451840 proved to be highly effective against Plasmodium falciparum - the parasite responsible for the deadliest form of malaria in humans, and Plasmodium vivax. It has also demonstrated activity against parasites that have developed resistance against current standard therapies. ACT-451840 appears to have a mode of action distinct from current antimalarial drugs, including artemisinins and quinolones. The drug has a rapid onset of action, no erythrocytic stage specificity, and shows reduction of gametocyte infectivity. The findings, which were recently published in the journal PLOS Medicine, are the result of Actelion's collaboration with academia.

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

The above information contains certain "forward-looking statements", relating to the company's business, which can be identified by the use of forward-looking terminology such as "estimates", "believes", "expects", "may", "are expected to", "will", "will continue", "should", "would be", "seeks", "pending" or "anticipates" or similar expressions, or by discussions of strategy, plans or intentions. Such statements include descriptions of the company's investment and research and development programs and anticipated expenditures in connection therewith, descriptions of new products expected to be introduced by the company and anticipated customer demand for such products and products in the company's existing portfolio. Such statements reflect the current views of the company with respect to future events and are subject to certain risks, uncertainties and assumptions. Many factors could cause the actual results, performance or achievements of the company to be materially different from any future results, performances or achievements that may be expressed or implied by such forward-looking statements. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those described herein as anticipated, believed, estimated or expected.

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Actelion Pharmaceuticals Ltd
Gewerbestrasse 16 Allschwil Switzerland

ISIN: CH0010532478;