Company: OCEA
Filing Date: 2025-04-08
Form Type: 10-K
Source: 0001641172-25-003155
Chunk: 2091

Company: Ocean Biomedical, Inc.
Filing Date: 2025-04-08
Form: 10-K
Item: Item 1A
Chunk 2091
---
GARP

Our
belief that PfGARP is a high value druggable target for anti-malarial drug development is based on PfGARP’s surface expression
on infected RBCs, the absence of any significant amino acid homology with human host proteins, and the ability of antibody binding to
PfGARP to kill parasites in vitro within 12-24 hours by activating parasite programed cell suicide.

32

To
develop a drug based on PfGARP binding, Dr. Kurtis screened a small molecule library to identify compounds that inhibit the binding of
anti-PfGARP antibody to PfGARP protein. Dr. Kurtis reasoned that compounds which bind to the same region of PfGARP that is targeted by
the parasite-lethal anti-PfGARP antibodies would be enriched for effective anti-malarials. Dr. Kurtis screened 6,400 compounds using
an assay that detects inhibition of binding of anti-PfGARP antibodies to immobilized PfGARP protein. Dr. Kurtis identified one compound
as having anti-parasite activity.

Dr.
Kurtis then conducted a limited Structure Activity Relationship, or SAR, campaign, evaluating 33 additional compounds with similarity
to the structure of the first compound identified. Dr. Kurtis identified one compound with enhanced parasite killing activity compared
to the original compound. This molecule has an IC50 (concentration of drug that results in half of the maximal killing effect)
of between 1 and 4.8 uM in wild type parasites (3D7 strain) and no activity in a parasite strain that has had the PfGARP gene deleted
(3D7 PfGARP KO) (see Fig 13). This result demonstrates both the specificity of drug activity for PfGARP, as well as the lack of general
toxicity to eukaryotic cells. Toxicity assessments show no loss of viability in multiple mammalian cell lines at up to 400 uM, which
was the highest concentration tested. These data are consistent with a selectivity index (ratio of IC50 for mammalian cells/IC50
for parasites) greater than 100.

Figure
13. Molecule kills P. falciparum parasites. 3D7 (top) or 3D7 PfGARP KO (bottom) parasites were synchronized to the ring stage and incubated
with a dilution series of compounds or media control for 48 hours followed by quantification of parasitemia by p