Investigational human monoclonal antibody in Phase Ib development for the treatment of transthyretin amyloid cardiomyopathy, a systemic, progressive and fatal condition.

Alexion, AstraZeneca’s Rare Disease group, has entered into an exclusive global collaboration and licence agreement with Neurimmune AG for NI006, an investigational human monoclonal antibody currently in Phase Ib development for the treatment of transthyretin amyloid cardiomyopathy (ATTR-CM). NI006 specifically targets misfolded transthyretin and is designed to directly address the pathology of ATTR-CM by enabling removal of amyloid fibril deposits in the heart, with the potential to treat patients with advanced ATTR-CM.

Under the agreement, Alexion will be granted an exclusive worldwide licence to develop, manufacture and commercialise NI006.

ATTR-CM is a systemic, progressive and fatal condition that leads to progressive heart failure and high rate of fatality 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

Marc Dunoyer, Chief Executive Officer, Alexion, said: “With 30 years of experience in developing medicines for people with rare diseases, Alexion is uniquely positioned to advance innovative science for small patient populations who are frequently underdiagnosed. We look forward to applying this expertise to the development of NI006, which is designed to clear cardiac amyloid fibril deposits with the potential to improve cardiac function for patients living with advanced ATTR-CM, who are currently underserved by existing treatment options.”

There is a significant unmet medical need for patients with various types and levels of severity of amyloidosis that may require multiple mechanisms of action to address those needs. NI006, an ATTR depleter, adds a novel and complementary approach to AstraZeneca and Alexion’s pipeline of investigational therapies focused on amyloidosis and strengthens our broader commitment to addressing cardiomyopathies that can lead to heart failure.

Financial considerations

Alexion will pay Neurimmune an upfront payment of $30m with the potential for additional contingent milestone payments of up to $730m upon achievement of certain development, regulatory and commercial milestones, as well as low-to-mid teen royalties on net sales of any approved medicine resulting from the collaboration.

Neurimmune will continue to be responsible for completion of the current Phase Ib clinical trial on behalf of Alexion, and Alexion will pay certain trial costs. Alexion will be responsible for further clinical development, manufacturing and commercialisation.

The transaction is expected to close following satisfaction of customary closing conditions and regulatory clearances.

Notes

Heart failure

Heart failure (HF) is a life-threatening chronic disease that prevents the heart from pumping sufficient levels of blood around the body. HF affects approximately 64 million people worldwide. HF remains as fatal as some of the most common cancers in both men (prostate and bladder cancers) and women (breast cancer).⁵ Chronic HF is the leading cause of hospitalisation for those over the age of 65 and represents a significant clinical and economic burden.⁶

AstraZeneca’s ambition is to be the leading company in HF, expanding from Forxiga today in heart failure with reduced ejection fraction (HFrEF), to the full HF spectrum including cardiomyopathies. AstraZeneca is investing in multiple investigational therapies with diverse mechanisms of action to address the spectrum of patient need in this area.

ATTR-CM

Cardiomyopathy due to ATTR is caused by aging or genetic mutations resulting in misfolded TTR protein and accumulation as amyloid fibrils in the cardiac myocardium. In patients with ATTR-CM, both the mutant and wild type TTR protein builds up as fibrils in tissues, including the heart. 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^3,4; however, many of those patients remain undiagnosed.

NI006

NI006 is an investigational human monoclonal antibody that specifically targets misfolded transthyretin and is designed to directly address the pathology of ATTR-CM by enabling removal of amyloid fibril deposits in the heart.

Alexion
Alexion, AstraZeneca Rare Disease, is the group within AstraZeneca focused on rare diseases, created following the 2021 acquisition of Alexion Pharmaceuticals, Inc. As a leader in rare diseases for nearly 30 years, Alexion is focused on serving patients and families affected by rare diseases and devastating conditions through the discovery, development and commercialisation of life-changing medicines. Alexion focuses its research efforts on novel molecules and targets in the complement cascade and its development efforts on haematology, nephrology, neurology, metabolic disorders, cardiology and ophthalmology. Headquartered in Boston, Massachusetts, Alexion has offices around the globe and serves patients in more than 50 countries.

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.

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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. 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.
4. 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.
5. Mamas MA et al. Do Patients Have Worse Outcomes in Heart Failure than in Cancer? A Primary Care-Based Cohort Study with 10-year Follow-up in Scotland. Eur J Heart Fail 2017; 19(9):1095–104.
6. Azad N, Lemay G. Management of Chronic Heart Failure in the Older Population. J Geriatr Cardiol 2014; 11(4):329–37.