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^PrWAINUA™ eplontersen injection

THE MECHANISM OF hATTR & THE MECHANISM OF ACTION AND PHARMACODYNAMICS OF WAINUA™*

WAINUA is indicated for the treatment of polyneuropathy associated with stage 1 or stage 2 hATTR in adults.¹

hATTR: hereditary transthyretin-mediated amyloidosis. * Clinical significance unknown.

Mechanism of disease: hATTR*

This presentation provides information on the mechanism of disease, which may not reflect the mechanism of the product or its benefits. WAINUA is not indicated for the treatment of polyneuropathy associated with hATTR in adults beyond stages 1 and 2.

* Clinical significance unknown.

The transthyretin protein, or TTR, is primarily synthesized in the liver and delivers thyroxine and retinol throughout the body.

The transthyretin protein, or TTR, is primarily synthesized in the liver and delivers thyroxine and retinol throughout the body.^2,3

Hereditary TTR amyloidosis, or hATTR, is caused by a point mutation that leads to the dissociation of the TTR tetrameric protein into monomers that misfold and aggregate into insoluble amyloid fibrils.

DNA
mRNA
TTR Tetramer
Amyloid Fibrils

Hereditary TTR amyloidosis, or hATTR, is caused by a point mutation that leads to the dissociation of the TTR tetrameric protein into monomers that misfold and aggregate into insoluble amyloid fibrils.^2,3

In patients with polyneuropathy associated with hATTR, these fibrils deposit into organs and tissues throughout the body.

WAINUA is not indicated for the treatment of polyneuropathy associated with hATTR in adults beyond stages 1 and 2.

In patients with polyneuropathy associated with hATTR, these fibrils deposit into organs and tissues throughout the body.^2,3

WAINUA’s MOA*

MOA: mechanism of action.
* Clinical significance unknown.

WAINUA is a GalNAc-conjugated antisense oligonucleotide.

WAINUA is a GalNAc-conjugated antisense oligonucleotide (ASO)¹

WAINUA is a GalNAc-conjugated antisense oligonucleotide.¹

The GalNAc conjugation enables targeted hepatocyte delivery.

Hepatocyte
WAINUA
GalNAc

The GalNAc conjugation enables targeted hepatocyte delivery.¹

Endosome

As a silencer of transthyretin…

WAINUA

As a silencer of transthyretin,

…WAINUA selectively binds to the TTR messenger RNA within the hepatocytes.

WAINUA
TTR Protein
Mutant and wild-type TTR mRNA

WAINUA selectively binds to the TTR messenger RNA within the hepatocytes.¹

This causes the degradation of both mutant and wild-type TTR mRNA and prevents TTR protein synthesis in the liver.

TTR Protein
Mutant and wild-type TTR mRNA

This causes the degradation of both mutant and wild-type TTR mRNA and prevents TTR protein synthesis in the liver.¹

Preventing the synthesis of TTR protein in the liver results in significant reductions in the levels of mutated and wild-type TTR protein secreted by the liver into the circulation.

Preventing the synthesis of TTR protein in the liver results in significant reductions in the levels of mutated and wild-type TTR protein secreted by the liver into the circulation.¹

Pharmacodynamic results*

* Clinical significance unknown.

In the pivotal Phase III study of WAINUA in adult patients with polyneuropathy associated with hATTR, a decrease in serum TTR concentration was observed as early as Week 5. At Week 35, there was an 81.2% reduction from baseline in the least squares mean serum TTR concentration.

Administration of WAINUA every 4 weeks led to an 81.2% reduction from baseline in the least squares mean serum TTR concentration at Week 35 (vs. -14.8% with external placebo; p<0.0001)¹

In the pivotal Phase III study of WAINUA in adult patients with polyneuropathy associated with hATTR, a decrease in serum TTR concentration was observed as early as Week 5. At Week 35, there was an 81.2% reduction from baseline in the least squares mean serum TTR concentration.¹

See WAINUA.ca/trial-design for an overview of the study.

WAINUA is the first and only TTR silencer available for once-monthly self-injection with an autoinjector.

Autoinjector

WAINUA is the first and only TTR silencer available for once-monthly self-injection with an autoinjector^1,4*†‡

Visual for illustrative purposes only.

* Clinical significance unknown.

† Comparative clinical significance has not been established.

‡ Patients or caregivers may administer WAINUA after proper training, with medical follow-up as necessary.¹ See the WAINUA Product Monograph for complete dosing and administration instructions.

IMPORTANT SAFETY INFORMATION

Please consult the Product Monograph at wainua-en.azpm.ca for important information about:

• Relevant warnings and precautions regarding reduced serum vitamin A levels and recommended supplementation, driving and operating machinery, potential risk of ocular symptoms, use in pregnant or breastfeeding women, and risks related to reproductive health including teratogenic risk.

• Conditions of clinical use, adverse reactions, drug interactions, and dosing instructions.

The Product Monograph is also available by calling 1-877-404-8277 or emailing ask-medical@astrazeneca.ca.

References

1. WAINUA™ Product Monograph. AstraZeneca Canada Inc. June 19, 2024.

2. Alcantara M, Mezei MM, Bakes SK, et al. Canadian Guidelines for Hereditary Transthyretin Amyloidosis Polyneuropathy Management. Can J Neurol Sci. 2022;49:7-18.

3. Coelho T, Marques Jr W, Dasgupta NR, et al. Eplontersen for hereditary transthyretin amyloidosis with polyneuropathy. JAMA. 2023;330(15):1448-1458.

4. Data on file. AstraZeneca Canada Inc. June 26, 2024.

AstraZeneca
Reviewed by PAAB
IMC

WAINUA™ is a trademark of AstraZeneca AB, used under license by AstraZeneca Canada Inc. The AstraZeneca logo is a registered trademark of AstraZeneca AB, used under license by AstraZeneca Canada Inc.

© AstraZeneca Canada Inc. 2024

CA-9351E