REG - AstraZeneca PLC - AstraZeneca, Ionis to collaborate on eplontersen

AstraZenecaAnnouncement

07/12/2021 07:00

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RNS Number : 8023U  AstraZeneca PLC  07 December 2021

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-L(RX.) 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-CM(4,5) and 10,000
- 40,000 patients with ATTR-PN(2).

 

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 (http://www.astrazeneca.com/) and follow the
Company on Twitter @AstraZeneca (https://twitter.com/AstraZeneca) .

 

Contacts

For details on how to contact the Investor Relations Team, please click here
(https://www.astrazeneca.com/investor-relations.html#Contacts) . For Media
contacts, click here (https://www.astrazeneca.com/media-centre/contacts.html)
.

 

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

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