Company: OCEA
Filing Date: 2025-04-08
Form Type: 10-K
Source: 0001641172-25-003155
Chunk: 2496

Company: Ocean Biomedical, Inc.
Filing Date: 2025-04-08
Form: 10-K
Item: Item 1
Chunk 2496
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 fragment, or Fab, of this antibody also killed parasites in culture. These data confirmed that anti-PfGARP-mediated killing
occurs in the absence of complement, cellular effector functions, or antigen cross-linking. We expect that a humanized version of this
antibody will form the basis for our ODA-611 program.

Figure
12. Monoclonal anti-PfGARP kill parasites. Anti-PfGARP mAb kills parasites. Ring stage 3D7 parasites were cultured in the presence of
media alone, normal mouse IgG (1 mg/ml) or anti-PfGARP mAbs (mAb 7857 or mAb 7899, at 1 mg/ml).

ODA-579—small
molecule targeting PfGARP

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