Author Listing - Lead/ Submitting Author (we will be communicating with this individual): Name, Institution, City and State where the work was done. Co-authors will be added in a separate section.
Julian D. Gillmore, National Amyloidosis Centre, Division of Medicine, University College London, Royal Free Hospital, London, UK

Main Body of the Abstract
Introduction:
In the treatment of AL and AA amyloidosis, better outcomes are associated with lower circulating concentrations of amyloidogenic serum free light chains (Palladini, et al. J Clin Oncol. 2012) and serum amyloid A protein (Lachmann, et al. N Engl J Med. 2007). In ATTR amyloidosis, the relationship between residual serum TTR concentrations ([TTR]) and clinical outcomes has not been established. We report [TTR] following administration of investigational CRISPR-based therapy NTLA-2001 in the first-in-human trial with the aim of enabling the development of biomarker-based response criteria in ATTR amyloidosis.
Methods:
In the ongoing NTLA-2001 phase 1 trial (NCT04601051), 62 subjects (ages 19-86; 9 women; 33 ATTRv-PN; 29 ATTR-CM) received weight-based (0.3, 0.7, or 1.0mg/kg) or fixed-dose (55 or 80mg) one-time infusions. Total circulating [TTR] was measured by immunoassay to detect total (wild type and mutant) [TTR] at pretreatment and predetermined times post infusion. Data were collected through 730 days (0.3mg/kg cohort).
Results:
Median (interquartile range [IQR]) absolute [TTR] measured at baseline was 213.2ug/mL (158.0-268.8). Median (IQR) percent reduction from baseline for [TTR] on Day 28 was 91.4% (88.2%-94.2%) among all 62 subjects. Median (IQR) absolute [TTR] measured on Day 28 was 16.9ug/mL (10.8-23.6) and remained stable thereafter. Median (IQR) maximum [TTR] change from Day 28 onward was -1.4ug/mL (-4.7-1.7). NTLA-2001 was generally well tolerated; most adverse events were mild in severity.
Conclusions:
The consistently low and stable absolute [TTR] levels achieved with NTLA-2001 could facilitate development of biomarker-based response criteria in ATTR amyloidosis, analogous to those in other systemic amyloidosis.

**Author Listing - Lead/ Submitting Author (we will be communicating with this individual): Name, Institution, City and State where the work was done. Co-authors will be added in a separate section.**
Julian D. Gillmore, National Amyloidosis Centre, Division of Medicine, University College London, Royal Free Hospital, London, UK

**Main Body of the Abstract**
**Introduction:**
In the treatment of AL and AA amyloidosis, better outcomes are associated with lower circulating concentrations of amyloidogenic serum free light chains (Palladini, et al. _J Clin Oncol._ 2012) and serum amyloid A protein (Lachmann, et al. _N Engl J Med._ 2007). In ATTR amyloidosis, the relationship between residual serum TTR concentrations ([TTR]) and clinical outcomes has not been established. We report [TTR] following administration of investigational CRISPR-based therapy NTLA-2001 in the first-in-human trial with the aim of enabling the development of biomarker-based response criteria in ATTR amyloidosis.
**Methods:**
In the ongoing NTLA-2001 phase 1 trial (NCT04601051), 62 subjects (ages 19-86; 9 women; 33 ATTRv-PN; 29 ATTR-CM) received weight-based (0.3, 0.7, or 1.0mg/kg) or fixed-dose (55 or 80mg) one-time infusions. Total circulating [TTR] was measured by immunoassay to detect total (wild type and mutant) [TTR] at pretreatment and predetermined times post infusion. Data were collected through 730 days (0.3mg/kg cohort).
**Results:**
Median (interquartile range [IQR]) absolute [TTR] measured at baseline was 213.2ug/mL (158.0-268.8). Median (IQR) percent reduction from baseline for [TTR] on Day 28 was 91.4% (88.2%-94.2%) among all 62 subjects. Median (IQR) absolute [TTR] measured on Day 28 was 16.9ug/mL (10.8-23.6) and remained stable thereafter. Median (IQR) maximum [TTR] change from Day 28 onward was -1.4ug/mL (-4.7-1.7). NTLA-2001 was generally well tolerated; most adverse events were mild in severity.
**Conclusions:**
The consistently low and stable absolute [TTR] levels achieved with NTLA-2001 could facilitate development of biomarker-based response criteria in ATTR amyloidosis, analogous to those in other systemic amyloidosis.

Enabling the development of serum TTR as a biomarker for treatment of ATTR amyloidosis PC103 (#151)

We invite you to attend the XIX International Symposium on Amyloidosis to be held in Rochester, MN.

This symposium is organized as a hybrid meeting (with the focus on in-person) held from Sunday, May 26 through Thursday, May 30, 2024.

Together with the ISA Board and members of Mayo Clinic, a very attractive scientific hybrid program is being planned. The program will cover a variety of types of systemic amyloidosis: ATTR (hereditary and wild-type), AL (light-chain), AA and less frequent forms. There will be key lectures, specific symposia including those company sponsored, oral presentations and poster sessions of accepted abstracts.

COURSE DESCRIPTION
This program will provide a comprehensive review of state-of-the-art education in systemic amyloidosis: basic science, pathophysiology, diagnosis, current and emerging treatments. Scientific presentations will include competitive oral and poster abstracts. The rapid evolution of scientific discovery and expanding treatment options has created tremendous interest in the field and this meeting will fill and important gap in educating scientists and clinicians.