a8026u
FORM 6-K
SECURITIES
AND EXCHANGE COMMISSION
Washington,
D.C. 20549
Report
of Foreign Issuer
Pursuant
to Rule 13a-16 or 15d-16 of
the
Securities Exchange Act of 1934
For the
month of December
2021
Commission
File Number: 001-11960
AstraZeneca PLC
1
Francis Crick Avenue
Cambridge
Biomedical Campus
Cambridge
CB2 0AA
United
Kingdom
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AstraZeneca PLC
INDEX
TO EXHIBITS
1.
AstraZeneca, Ionis to collaborate on eplontersen
7 December 2021 07:00 GMT
AstraZeneca and Ionis sign deal to develop and commercialise
eplontersen
Liver-targeted antisense therapy in Phase III development for the
treatment of transthyretin amyloidosis, a
systemic, progressive and fatal condition
AstraZeneca has entered into a new global development and
commercialisation agreement with Ionis Pharmaceuticals, Inc.
(Ionis) for eplontersen, formerly known as IONIS-TTR-LRX. Eplontersen
is a ligand-conjugated antisense
investigational medicine currently in Phase III clinical trials for
amyloid transthyretin cardiomyopathy (ATTR-CM)
and amyloid transthyretin polyneuropathy
(ATTR-PN). It is designed to reduce the production of transthyretin
(TTR protein) to treat both hereditary and non-hereditary forms of
TTR amyloidosis (ATTR).
The companies will jointly develop and commercialise eplontersen in
the US, while AstraZeneca will develop and commercialise it in the
rest of the world, except in Latin America.
ATTR-CM is a systemic, progressive and fatal condition that leads
to progressive heart
failure and death within four years from
diagnosis.1 It
remains underdiagnosed and its prevalence is thought to be
underestimated due to a lack of disease awareness and the
heterogeneity of symptoms.2 Hereditary
ATTR-PN is a debilitating disease that leads to peripheral nerve
damage with motor disability within five years of diagnosis and,
without treatment, is generally fatal within a
decade.3
Mene Pangalos, Executive Vice President, BioPharmaceuticals
R&D, AstraZeneca, said:
"Eplontersen has the potential
to halt the progression of TTR-mediated amyloidosis, irrespective
of whether it's caused by genetic mutations or aging. Thanks to its
precise liver-targeting properties, it also has the potential to be
a best-in-class treatment for patients suffering from this
devastating disease and who currently have limited
options."
Hereditary ATTR-PN is expected to be the first indication for which
the companies will seek regulatory approval for eplontersen, with
the potential to file a new drug application with the US Food and
Drug Administration by the end of 2022.
Financial considerations
AstraZeneca will pay Ionis an upfront payment of $200m and
additional conditional payments of up to $485m following regulatory
approvals. It will also pay up to $2.9bn of sales-related
milestones based on sales thresholds between $500m and $6bn, plus
royalties in the range of low double-digit to mid-twenties
percentage depending on the region. The collaboration includes
territory-specific development, commercial and medical affairs
cost-sharing provisions.
The transaction will be funded with cash and is expected to be
neutral to Core earnings in 2021. It will be accounted for as an
intangible asset acquisition, recognised initially at the upfront
amount, with any potential future milestone payments capitalised
into the intangible asset as they are recognised.
Ionis will continue to manufacture and supply eplontersen for the
existing clinical studies and process qualification. AstraZeneca
will be responsible for commercial supply, with transition timing
to be agreed by both parties. AstraZeneca will book all sales
generated under the agreement.
The transaction is expected to close in the fourth quarter of 2021,
subject to customary closing conditions and regulatory clearances.
The transaction does not impact the AstraZeneca's financial
guidance for 2021.
Notes
Eplontersen
Eplontersen is a ligand-conjugated antisense (LICA) investigational
medicine designed to reduce the production of transthyretin, or TTR
protein, to treat all types of ATTR, a systemic, progressive and
fatal disease.
TTR Amyloidosis (ATTR)
Cardiomyopathy and polyneuropathy due to ATTR are caused by aging
or genetic mutations resulting in misfolded TTR protein and
accumulation as amyloid fibrils in the cardiac myocardium and
peripheral nerves, respectively. In patients with ATTR, both the
mutant and wild type TTR protein builds up as fibrils in tissues,
such as the peripheral nerves, heart, gastrointestinal system,
eyes, kidneys, central nervous system, thyroid and bone marrow. The
presence of TTR fibrils interferes with the normal functions of
these tissues. As the TTR protein fibrils enlarge, more tissue
damage occurs and the disease worsens, resulting in poor quality of
life and eventually death. Worldwide, there are an estimated
300,000 - 500,000 patients with ATTR-CM4,5 and
10,000 - 40,000 patients with ATTR-PN2.
AstraZeneca
AstraZeneca (LSE/STO/Nasdaq: AZN) is a global, science-led
biopharmaceutical company that focuses on the discovery,
development, and commercialisation of prescription medicines in
Oncology, Rare Diseases, and BioPharmaceuticals, including
Cardiovascular, Renal & Metabolism, and Respiratory &
Immunology. Based in Cambridge, UK, AstraZeneca operates in over
100 countries and its innovative medicines are used by millions of
patients worldwide. Please visit astrazeneca.com and
follow the Company on Twitter @AstraZeneca.
Contacts
For details on how to contact the Investor Relations Team, please
click here.
For Media contacts, click here.
References
1. Lauppe RE, et al. Nationwide prevalence and characteristics of
transthyretin amyloid cardiomyopathy in
Sweden. Open Heart. 2021 Oct;8(2):e001755. doi:
10.1136/openhrt-2021-001755.
2. González-Duarte A, et al. Impact of non-cardiac clinicopathologic
characteristics on survival in transthyretin amyloid
polyneuropathy. Neurol Ther. 2020;9(1):135-149.
doi:10.1007/s40120-020-00183-7.
3. Cortese A, et al. Diagnostic challenges in hereditary
transthyretin amyloidosis with polyneuropathy: avoiding
misdiagnosis of a treatable hereditary
neuropathy. J Neurol Neurosurg
Psychiatry. 2017
May;88(5):457-458. doi:
10.1136/jnnp-2016-315262.
4. Mohamed-Salem L, et al. Prevalence of wild type ATTR assessed as
myocardial uptake in bone scan in the elderly
population. Int J
Cardiol. 2018 Nov
1;270:192-196. doi:
10.1016/j.ijcard.2018.06.006.
5. Cuscaden C, et al. Estimation of prevalence of transthyretin (ATTR)
cardiac amyloidosis in an Australian subpopulation using bone scans
with echocardiography and clinical
correlation. J Nucl
Cardiol. 2020 May 8. doi:
10.1007/s12350-020-02152-x.
Adrian Kemp
Company Secretary
AstraZeneca PLC
SIGNATURES
Pursuant
to the requirements of the Securities Exchange Act of 1934, the
Registrant has duly caused this report to be signed on its behalf
by the undersigned, thereunto duly authorized.
Date:
7 December
2021
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By: /s/
Adrian Kemp
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Name:
Adrian Kemp
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Title:
Company Secretary
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