Wainua.ca | Efficacy Data

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WAINUA significantly slowed progression of neuropathy as measured by the mNIS+7 composite score vs. external placebo at Week 35 and through Week 66 (co-primary efficacy endpoint)¹*

Change in the mNIS+7 composite score through 66 weeks^1,2

LSM change from baseline at Week 35 (interim analysis): 0.22 WAINUA vs. 9.22 external placebo (difference: -9.0; 95% CI: -13.5, -4.5; p<0.0001)
LSM change from baseline at Week 66 (final analysis): 0.30 WAINUA vs. 25.06 external placebo (difference: -24.76; 95% CI: -30.96, -18.56; p<0.0001)

Adapted from the WAINUA Product Monograph and Coelho T, et al.^1,2

The statistical significance of the Week 66 results was not formally tested due to statistically significant results at Week 35.¹

An observed effect on the mNIS+7 composite score was consistent and sustained with WAINUA through the end of treatment at Week 85¹*

Change in the mNIS+7 composite score through 85 weeks^1,3

Adapted from the WAINUA Product Monograph and Coelho T, et al.^1,3

Week 85 data are not available for the external placebo group, as the treatment period in the NEURO-TTR study was limited to 66 weeks.¹

The mNIS+7 is an objective assessment of neuropathy with a range of -22.3 to 346.3 points, where higher scores represent a greater severity of disease.¹

The NIS measures deficits in:¹

Cranial nerve function
Muscle strength
Reflexes
Sensations

And the Modified +7 composite score measures:¹

Heart rate response to deep breathing
Quantitative sensory testing (touch-pressure and heat-pain)
Peripheral nerve electrophysiology

WAINUA significantly improved quality of life as measured by the Norfolk QoL-DN total score vs. external placebo at Week 35 and through Week 66 (co-primary efficacy endpoint)¹*

Change in the Norfolk QoL-DN total score through 66 weeks¹

Change in the Norfolk QoL-DN total score through 66 weeks11,2

LSM change from baseline at Week 35 (interim analysis): -3.12 WAINUA vs. 8.67 external placebo (difference: -11.79; 95% CI: -16.82, -6.76; p<0.0001; key secondary endpoint at this timepoint)
LSM change from baseline at Week 66 (final analysis): -5.50 WAINUA vs. 14.24 external placebo (difference: -19.74; 95% CI: -25.63, -13.84; p<0.0001)

Adapted from the WAINUA Product Monograph.¹

The statistical significance of the Week 66 results was not formally tested due to statistically significant results at Week 35.¹

Given the subjective nature of the Norfolk QoL-DN assessment, care should be taken when interpreting the significance of this data, particularly in the context of an open-label trial.¹

The mean Norfolk QoL-DN total score remained stable through Week 85 with WAINUA¹*

Change in the Norfolk QoL-DN total score through 85 weeks^1,3

Adapted from the WAINUA Product Monograph and Coelho T, et al.^1,3

Week 85 data are not available for the external placebo group, as the treatment period in the NEURO-TTR study was limited to 66 weeks.¹

The Norfolk QoL-DN questionnaire is a patient-reported assessment. The version used in the trial had a range from -4 to 136 points, where higher scores represent greater impairment. It evaluates the subjective experience of neuropathy in the following domains:¹

Physical functioning/large fibre neuropathy
Activities of daily living
Symptoms

Small fibre neuropathy
Autonomic neuropathy

WAINUA demonstrated statistically significant superiority in neuropathy symptom severity vs. external placebo, as measured by the change from baseline in NSC score (a patient-answered questionnaire) at Week 66 (secondary endpoint)^1,2

Change in NSC score through 66 weeks^2,3

Adjusted mean change from baseline at Week 66 (final analysis): -0.03 WAINUA vs. 8.2 external placebo (difference: -8.2; 95% CI: -10.7, -5.8; p<0.001)

Adapted from Coelho T, et al.^2,3

NSC benefits at Week 66 remained consistent through Week 85 with WAINUA.¹

Week 85 data are not available for the external placebo group, as the treatment period in the NEURO-TTR study was limited to 66 weeks.¹

The NSC is a patient-answered questionnaire in which higher scores represent worse symptoms. It is used to quantify the type, distribution, and severity of:¹

Muscle weakness
Sensory symptoms

Pain symptoms
Autonomic symptoms

WAINUA demonstrated statistically significant superiority in the change from baseline in the physical component score (PCS) of SF-36 vs. external placebo at Week 65 (secondary endpoint)^1,2

Change in SF-36 PCS score through 65 weeks^2,3

Adjusted mean change from baseline at Week 65 (final analysis): 0.9 WAINUA vs. -4.5 external placebo (difference: 5.3; 95% CI: 3.2, 7.4; p<0.001)

Adapted from Coelho T, et al.^2,3

SF-36 PCS results continued to trend toward improvement through Week 85 with WAINUA.¹

Week 85 data are not available for the external placebo group, as the treatment period in the NEURO-TTR study was limited to 66 weeks.¹

The SF-36 PCS refers to the physical component score of a health survey in which higher scores represent better physical health. The version used in NEURO-TTRansform included 4 scales assessing:¹

Physical function
Role limitations caused by physical problems

Bodily pain
General health

WAINUA demonstrated statistically significant superiority in the change from baseline in the polyneuropathy disability measure (PND score) vs. external placebo at Week 65 (p<0.05; secondary endpoint)^1,2

Change in PND score at Week 65²

Adapted from Coelho T, et al.²

PND benefits at Week 66 remained consistent through Week 85 with WAINUA.¹

Week 85 data are not available for the external placebo group, as the treatment period in the NEURO-TTR study was limited to 66 weeks.¹

The PND categorises disability by mobility (e.g., need for stick, crutch, wheelchair, or bed), with a higher PND score representing worse disability. The scores are defined as follows:^1,2

I = Unassisted walking
II = Impaired unassisted walking
IIIa = Assisted walking with 1 cane or crutch

IIIb = Assisted walking with 2 canes or crutches
IV = Confined to a wheelchair or bedridden

WAINUA demonstrated statistically significant superiority in nutritional status as measured by the change from baseline in mBMI vs. external placebo at Week 65 (p<0.001; secondary endpoint)^1,2

Change in mBMI through 65 weeks^2,3

Adjusted mean change from baseline (kg/m² x g/L) at Week 65 (final analysis): -8.1 WAINUA vs. -90.8 external placebo (difference: 82.7; 95% CI: 54.6, 110.8; p<0.001)

Adapted from Coelho T, et al.^2,3

mBMI benefits at Week 66 remained consistent through Week 85 with WAINUA.¹

Week 85 data are not available for the external placebo group, as the treatment period in the NEURO-TTR study was limited to 66 weeks.¹

Modified body mass index (BMI × serum albumin) is an acceptable method of assessing nutritional status in ATTR.¹

Higher mBMI scores represent better nutritional status and are considered to be an indicator of longer survival in hATTR PN patients.¹

See NEURO-TTRansform trial design

mNIS+7: modified Neuropathy Impairment Score+7; Norfolk QoL-DN: Norfolk Quality of Life – Diabetic Neuropathy; NSC: neuropathy symptoms and change; SF-36: short-form 36-item health survey (version 2); PCS: physical component score;

PND: polyneuropathy disability; mBMI: modified body mass index; TTR: transthyretin; LSM: least squares mean; CI: confidence interval; SD: standard deviation; EOT: end-of-treatment; BMI: body mass index; ATTR: transthyretin-mediated amyloidosis;

hATTR: hereditary transthyretin-mediated amyloidosis; PN: polyneuropathy.

* At baseline, the mean mNIS+7 composite score was 81.3 (SD 43.4) and the mean Norfolk QoL-DN
total score was 44.1 (SD 26.6).¹

References: 1. WAINUA® Product Monograph. AstraZeneca Canada Inc. August 26, 2025. 2. Coelho T, Marques Jr W, Dasgupta
NR, et al. Eplontersen for hereditary transthyretin amyloidosis with polyneuropathy. JAMA. 2023;330(15):1448-1458.
3. Supplementary Online Content for: Coelho T, Marques Jr W, Dasgupta NR, et al. Eplontersen for hereditary transthyretin amyloidosis with polyneuropathy. JAMA. 2023;330(15):1448-1458.

WAINUA® Important Safety Information

WAINUA®

Efficacy Data

WAINUA significantly slowed progression of neuropathy as measured by the mNIS+7 composite score vs. external placebo at Week 35 and through Week 66 (co-primary efficacy endpoint)1*

An observed effect on the mNIS+7 composite score was consistent and sustained with WAINUA through the end of treatment at Week 851*

WAINUA significantly improved quality of life as measured by the Norfolk QoL-DN total score vs. external placebo at Week 35 and through Week 66 (co-primary efficacy endpoint)1*

The mean Norfolk QoL-DN total score remained stable through Week 85 with WAINUA1*

WAINUA demonstrated statistically significant superiority in neuropathy symptom severity vs. external placebo, as measured by the change from baseline in NSC score (a patient-answered questionnaire) at Week 66 (secondary endpoint)1,2

WAINUA demonstrated statistically significant superiority in the change from baseline in the physical component score (PCS) of SF-36 vs. external placebo at Week 65 (secondary endpoint)1,2

WAINUA demonstrated statistically significant superiority in the change from baseline in the polyneuropathy disability measure (PND score) vs. external placebo at Week 65 (p<0.05; secondary endpoint)1,2

WAINUA demonstrated statistically significant superiority in nutritional status as measured by the change from baseline in mBMI vs. external placebo at Week 65 (p<0.001; secondary endpoint)1,2

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WAINUA^® Important Safety Information

WAINUA^®

WAINUA significantly slowed progression of neuropathy as measured by the mNIS+7 composite score vs. external placebo at Week 35 and through Week 66 (co-primary efficacy endpoint)¹*

An observed effect on the mNIS+7 composite score was consistent and sustained with WAINUA through the end of treatment at Week 85¹*

WAINUA significantly improved quality of life as measured by the Norfolk QoL-DN total score vs. external placebo at Week 35 and through Week 66 (co-primary efficacy endpoint)¹*

The mean Norfolk QoL-DN total score remained stable through Week 85 with WAINUA¹*

WAINUA demonstrated statistically significant superiority in neuropathy symptom severity vs. external placebo, as measured by the change from baseline in NSC score (a patient-answered questionnaire) at Week 66 (secondary endpoint)^1,2

WAINUA demonstrated statistically significant superiority in the change from baseline in the physical component score (PCS) of SF-36 vs. external placebo at Week 65 (secondary endpoint)^1,2

WAINUA demonstrated statistically significant superiority in the change from baseline in the polyneuropathy disability measure (PND score) vs. external placebo at Week 65 (p<0.05; secondary endpoint)^1,2

WAINUA demonstrated statistically significant superiority in nutritional status as measured by the change from baseline in mBMI vs. external placebo at Week 65 (p<0.001; secondary endpoint)^1,2