Company: LIMN
Filing Date: 2025-01-16
Form Type: POS AM
Source: 0001104659-25-003835
Chunk: 355

Company: Liminatus Pharma, Inc.
Filing Date: 2025-01-16
Form: POS AM
Chunk 355
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 were observed in any parameter compared to the vehicle control group, supporting the determination of the No Observed Adverse Effect Level (NOAEL) at 100 mg/kg/ dose. Anti-drug antibody analysis, toxicokinetic parameters, organ weights, and macroscopic and microscopic examinations.

On Day 22, the combined sex mean C0, Cmax, and AUC0-168hr values of IBA101 at the NOAEL were:

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No C0 (Initial Plasma Concentration): 4,310,000 ng/mL

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Cmax (Maximum Plasma Concentration): 4,080,000 ng/mL

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AUC0-168hr (Area Under the Concetration-Time Curve): 359,000,000 hr*ng/mL.

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These toxicokinetic results suggest a good safety profile of IBA101 under the tested conditions and provide statistical evidence for its tolerability.

#### Efficacy-related studies
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CD47 antibody blocks interaction of CD47 and SIRPα

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A competitive ELISA assay demonstrated that the interaction between recombinant CD47 and recombinant SIRPα proteins was blocked by Hu3A5 in vitro.

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CD47 antibody promotes phagocytosis of live tumor cells by human macrophages.

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In vitro phagocytosis assay demonstrated that human macrophages promoted the uptake of live tumor cells in the presence of as low as > 0.1 micro grams/ml of CD47 mAb.

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Exclusive blockade of human CD47 on tumor cells with Hu3A5 in combination with check-point inhibitors induces a limited synergistic suppression of tumor growth.

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To assess how effectively CD47 blockade enhances anti-tumor responses, hCD47-expressing MC38 tumor cells were subcutaneously engrafted into normal C57BL/6 mice, and anti-human CD47 monoclonal antibodies were injected to specifically block the function of the hCD47 protein on tumor cells, allowing evaluation of the resulting increase in anti-tumor effects.

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This induced moderate delayed tumor growth.

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However, in combination with anti-PD-L1 and anti-TIGIT check-point inhibitors significant synergistic activity was observed where tumor growth was regressed and most of the mice became tumor-free.

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Global blockade of human CD47 on tumor and immune cells induces significant reduction of tumor growth.

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Investigated whether global effects of CD47 blockade would be beneficial if all cells including immune cells were expressing human CD47.

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Instillation of Hu3