About Amyloidosis

Overview, Disorder Types, & Improvement Prospects
A purple and cyan fibril graphicA purple and cyan fibril graphic

General Overview

Of Systemic Amyloidosis & The Patient Experience

Characterisation

Amyloid diseases are a diverse group of disorders, characterized by the deposition of amyloid protein fibrils in vital organs and tissues. There are approximately 30 different types of amyloidosis, each resulting from the misfolding and aggregation of a specific protein, and they are all severely debilitating, progressive, and often fatal.

Proven Treatments in Systemic Amyloidosis

Modulating amyloid proteins is a validated target in systemic amyloidosis. Therapies recently approved in ATTR amyloidosis have proven that reducing or stabilizing the pre-cursor protein leads to slowing disease progression. In AL amyloidosis, off-label plasma cell targeting agents including chemotherapy and Autologous Stem Cell Transplant, which both reduce the precursor protein, have also been shown to improve clinical outcomes. Reducing or stabilizing the pre-cursor protein in AL and ATTR amyloidosis results in the reduction of formation of new amyloid, but does not directly address already deposited toxic amyloid.

Diagnosis

There is a substantial unmet need to improve the diagnosis of amyloidosis in patients. The majority of systemic amyloidosis patients see more than four specialists and take more than 18 months to get an accurate diagnosis, with 25% of patients taking more than five years to get a correct diagnosis. Unfortunately, due to this prolonged process, a significant number of patients die without a diagnosis. Of the patients that do receive a diagnosis, there are a number of diagnostic procedures required with clear challenges in getting an early and accurate diagnosis. A misdiagnosis can be deadly and delayed diagnosis leads to poorer patient outcomes.

30 Subtypes

of Systemic Amyloidosis

4 Most Common Types of Systemic Amyloidosis

wtATTR
Wild-type Transthyretin Amyloidosis
Prevalence of the disease
>300K patients
in US, EU, & Japan
Disease overlaps and correlations with populations or other diseases and disorders.
13% of HFpEF patients
may have wtATTR
Common organs affected by the disease
Mainly manifests in heart and ligaments & tendons
Survival rates of the disease
Median Survival:
3-5 years
hATTR
Hereditary Transthyretin Amyloidosis
Prevalence of the disease
>50K patients
in US, EU, & Japan
Disease overlaps and correlations with populations or other diseases and disorders.
3-4% of African Americans carry the V122I (V142I) mutation
Common organs affected by the disease
Manifests in heart, nerves, GI, and kidneys
Survival rates of the disease
Median Survival: 3-15 years; 3-5 years with
cardiac involvement
AL
Light Chain Amyloidosis
Prevalence of the disease
>50K patients
in US, EU & Japan
Disease overlaps and correlations with populations or other diseases and disorders.
15-20% of MM patients have co-existing AL​
Common organs affected by the disease
Manifests in almost every organ: >70% have cardiac and/or kidney
Survival rates of the disease
Median Survival: 4 years;
6 months to 3 years
in cardiac patients
ALECT2
Leukocyte Chemotactic Factor 2 Amyloidosis
Prevalence of the disease
Unknown prevalence
Disease overlaps and correlations with populations or other diseases and disorders.
ALECT2 deposits found in~3% of Hispanic descendants
Common organs affected by the disease
Manifests mainly in kidney and liver

OtherTypes of Systemic Amyloidosis

Prevalence of the disease
Rare: <50K in aggregate
in US, EU & Japan
Common organs affected by the disease
Manifests in various organs, with about half affecting kidneys
A full list of 26 other less common types of amyloidosis

Shortcomings & Attralus Solutions

Strategies To Improve Diagnosis & Treatment

Diagnostic Pathway is Complicated

A prompt diagnosis is urgently needed, but for most patients, it takes over 18 months from first symptoms to confirmed diagnosis. For 25% of patients, it takes more than five years.

Diagnosis Lag

A significant portion of the long diagnostic timeframes is owed to an initial delay in suspicion of amyloidosis. Patients present with non-specific and seemingly unrelated cluster of symptoms such as fatigue, dyspnea, edema or GI issues. Most patients see more than four specialists before reaching a diagnosis.

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First-in-Class Diagnostic
Imaging Agent

The Attralus PET/CT imaging agent AT-01 has
the potential to provide a rapid and accurate diagnosis of
systemic amyloidosis.

Test Quantity,
Invasiveness, & Accuracy

Even after amyloid is suspected, the diagnostic pathway can be arduous and require numerous tests, including an invasive biopsy for most patients.  Current diagnostic tests only reveal an incomplete picture of the patient’s disease, often with amyloid
only confirmed in one organ.

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One Accurate,
Non-invasive Test

AT-01 has the potential to comprehensively measure amyloid deposition in organs throughout the whole body, to differentiate between subtypes of amyloidosis, and to monitor disease progression and treatment response.

Current Treatment is Limited or Non-existent for Systemic Amyloidosis

Attralus is developing novel pan-amyloid targeting agents to directly bind and remove toxic amyloid fibrils from organs and tissues throughout the body, with the potential to reverse disease pathology – going beyond current treatments that reduce the formation of amyloid fibrils and slow disease progression but do no remove amyloid from the body.

Current treatments reduce new amyloid fibril formation but do not actively remove existing toxic fibril deposits from tissues

When available, current treatment options for AL and ATTR do not directly address already deposited toxic amyloid in organs and tissues. These treatments have limited impact of later stage patients, which represent ~50% of the population.

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The Attralus therapeutic candidates are specifically designed to remove toxic amyloid aggregates and deposits

Attralus’s therapeutics target motifs that are universally and ubiquitously presented on all amyloid fibrils. This pan-amyloid binding profile allows Attralus’s therapeutics to target multiple types of amyloid fibrils including AL, ATTR, and ALECT2.

Only 1 out of 30 amyloid
disorders currently has
FDA-approved treatments

While there are treatments in two types of
amyloidosis (ATTR & AL), there remains a very high
unmet need with poor median survival & quality of life. 

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The Attralus therapeutic candidates 
can potentially address many types
of systemic amyloidosis

Not only do we have the potential to develop therapeutics to treat patients with any form of systemic amyloidosis, we also can potentially treat those with late-stage disease for whom current therapies have not shown significant impact. 

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