PIPELINES

 

AP-01

AP-01 is LNP-formulated composite siRNAs that work in concert to downregulate the expression of a cancer-specific transcript of the gene encoding MIR-1, a master regulator of invadopodia biogenesis and Wnt signaling in cancer cells. AP-01 is designed to simultaneously block the invasive growth and the distant metastasis of advanced cancers. Antapodia Nanotherapeutics leverages state-of-the-art and tissue-customized LNP technologies to target both liver and non-liver cancers. The company has completed more than 10 compelling POM/POC studies showing that systemic administration of AP-01 is able to shrink primary tumors and abolish distant metastasis and significantly lengthens survival in various models of TNBC, PDAC, and NSCLC (Figures 1-4). Intratumoral (IT) administration of AP-01 also leads to remarkable tumor shrinkage in orthotopic TNBC and HCC modes wherein loco-regional therapies are clinically applicable (Figures 5-7). The company is now testing AP-01 in PDX tumor metastasis models and optimizing its dosing schedule to further substantiate its anti-tumor efficacy and survival-lengthening effect.

TNBC: triple-negative breast cancer; PDAC: pancreatic ductal adenocarcinoma; NSCLC: non-small cell lung cancer; HCC: hepatocellular carcinoma; PDX: patient-derived xenograft.

Figure 1.  Systemic AP-01 therapy inhibits breast cancer metastasis and lengthens survival

(Metastasis control rate: 88.9%; lowering mortality by 87.7%)

Figure 1.  Systemic administration of AP-01 attenuates PDAC metastasis and lengthens survival(metastasis control rate = 79.4%; survival extension = 28%).

IV: intravenous; BLI: bioluminescence.

Figure 2.  Systemic AP-01 therapy inhibits pancreatic cancer metastasis and lengthens survival

(Metastasis control rate: 79.4%; extending survival by 33.3%)

Figure 2.  Systemic administration of AP-01 abolishes breast cancer metastasis.

Figure 3.  Systemic AP-01 therapy inhibits lung cancer dissemination and lengthens survival

(Metastasis control rate: 99.7%; extending survival by 41.8%)

Figure 3.  Combined local and systemic AP-01 treatment shrinks primary breast cancer and prevents pulmonary metastasis.

Figure 4.  Systemic AP-01 therapy shrinks orthotopic breast cancers, prevents metastasis and lengthens survival 
(Tumor growth inhibition: 81.2% [5 mg/kg]; metastasis control rate: 100%; extending survival by 74.6% [1 mg/kg] to 81.9% [5 mg/kg])

Figure 4.  Intratumoral (IT) AP-01 synergizes with Sorafenib in the treatment of HCC.

Figure 5.  Combined local and systemic AP-01 therapies shrink orthotopic breast cancers, prevent metastasis, and double the length of survival

(Tumor growth inhibition: 92.8% [AP-01 alone]; metastasis control rate: 100%; extending survival by 108.2% [AP-01 alone])

Figure 5.  Combined local and systemic AP-01 treatment shrinks primary TNBC and prevents pulmonary metastasis (tumor control rate = 92.8%; metastasis control rate = 100%).

IT: intratumoral; IP: intra-peritoneal; IV: intravenous

Figure 6.  Intratumoral AP-01 therapy synergizes with sorafenib in liver cancer treatment

(Tumor growth inhibition: 100% [AP-01 2.5 mg/kg])

Figure 6.  Intratumoral (IT) AP-01 synergizes with sorafenib in the treatment of HCC (tumor control rate = 100% [high dose]).

Figure 7.  Systemic AP-01 therapy shrinks orthotopic liver cancers, inhibits daughter nodules, and lengthens survival

(Tumor growth inhibition: 57.5%; lowering mortality by 81%)

Figure 7.  Systemic administration of AP-01 shows anti-tumor efficacy and lengthens survival in HCC(tumor control rate = 57.5%; survival extension > 30%).
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