**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.**
Aubin Michalon, Neurimmune, Schlieren, Switzerland

**Main Body of the Abstract**
Background: NI006 is a recombinant human antibody in development for the depletion of cardiac amyloid transthyretin (ATTR) in patients with ATTR-cardiomyopathy (ATTR-CM). To select a safe and potentially efficacious dose range for a first-in-human clinical phase 1b study, we developed a mechanistic pharmacokinetic and pharmacodynamic (PK/PD) model to predict NI006 effects on cardiac amyloid in patients.
Method: A three-compartmental PK/PD model was developed that integrated preclinical efficacy data together with physiological and disease-related parameters obtained from published literature.
Results: PK/PD predictions for maximum serum concentration and target occupancy supported 0.3 mg/kg monthly dosing as a suitable starting dose for a first-in-human trial with less than 0.1% target occupancy. The model predicted a time- and dose-dependent effect on cardiac amyloid removal with substantial depletion within 4-18 months at doses of 10 to 60 mg/kg. In contrast, only minor effects on amyloid depletion were predicted for monthly doses at or below 3 mg/kg. These predictions were in good agreement with the recently reported primary results of the phase 1b study with NI006 in ATTR-CM patients (NCT04360434).
Conclusion: This novel translational PK/PD model provided valuable predictions to guide the design of a first-in-human study of NI006 in ATTR-CM. Model results were instrumental in the selection of the dose range, dose escalation, dosing interval and study duration. Overall, the model predictions were in good agreement with the clinical study results, indicating the validity of this modeling approach to increase translational success.



Prediction of cardiac ATTR depletion by NI006 using mechanistic PK/PD modeling PC123 (#291)

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.