# Supplemental Grant Request to existing 5U01AG053247 - 03 - TK/PK Assay Analysis and Development

> **NIH NIH U01** · ACUMEN PHARMACEUTICALS, INC. · 2020 · $262,500

## Abstract

5U01AG053247-3 Supplemental Request Summary
The development of ACU-193 for Alzheimer’s disease is now reaching the final IND-enabling
portions of the non-clinical research, including first non-GLP followed by GLP toxicology
studies. Following completion of the toxicology studies, the current plan is to finalize and
submit an IND to FDA. The design of the Phase 1 protocol has been agreed on and the protocol
will be written early in 2020. Additionally, a Type C interaction with FDA occurred with a
meeting request made in December 2018. The FDA did not feel that a meeting was required but
provided written feedback in February 2019 to 3 questions posed in the Briefing Document. The
FDA made relatively minor requests for additional non-clinical data in the IND, which will be
provided. FDA agreed in principle to the study design as described in the Briefing Document,
although they did ask for a small increase in sample size in the single dose portion of the study
which will be done. First patient visit for the study is planned for 4Q2020.
In support of non-GLP toxicokinetic (TK/PK) dose-ranging studies, a basic
electrochemiluminescent immunoassay (ECLIA) method was developed and readily qualified for
measurement of ACU-193 in Cynomologous monkey plasma. In contrast, the same basic
method proved unacceptable when applied to plasma from Sprague Dawley rats. Specifically,
excessive imprecision was noted at the upper end of the assay dynamic range. This precluded
reliable quantification of the high ACU-193 concentrations anticipated in the planned dose-
ranging studies. A series of additional experiments revealed that interfering substances were
present in some but not all rats. Parallel development of a bridging ECLIA for detection and
characterization of Anti-Drug Antibodies (ADA) in serum from Cynomologous monkey and
Sprague Dawley rat revealed reactivity, sometimes quite high reactivity, in selected drug naïve
rats. No such reactivity was observed in sera obtained from Cynomolgus monkeys. The
interfering substances in the rat PK/TK assay and reactivity in the rat ADA assay were ultimately
determined to be rat anti-human immunoglobulin antibodies. When present, these antibodies
interfered with the measurement ACU-193 in rat plasma and behaved like ADAs in the serum of
treatment naïve rats. Unfortunately, funds originally intended to cover an anticipated,
straightforward development and qualification of the rat TK and rat ADA assays had to be spent
to define the cause of the problem and modify basic assay formats to resolve that underlying
issue. Supplemental funding is now being requested to cover the costs for completing the
initially planned development and qualification work. With this additional funding, we believe
that first patient visit for the clinical trial can begin without a delay.
Acumen Pharmaceuticals is thus requesting a $250,000 Supplemental Grant to the existing Grant
5U01AG053247 - 03 to complete the development of the rat TK/PK and AD...

## Key facts

- **NIH application ID:** 10083278
- **Project number:** 3U01AG053247-04S1
- **Recipient organization:** ACUMEN PHARMACEUTICALS, INC.
- **Principal Investigator:** Eric Siemers
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $262,500
- **Award type:** 3
- **Project period:** 2017-09-15 → 2021-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10083278

## Citation

> US National Institutes of Health, RePORTER application 10083278, Supplemental Grant Request to existing 5U01AG053247 - 03 - TK/PK Assay Analysis and Development (3U01AG053247-04S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10083278. Licensed CC0.

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