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Antapodia 01 (AP-01)

AP-01 is a lipid nanoparticle (LNP)-formulated mixture of siRNAs that target a novel cancer-specific transcript of the gene encoding MIR-01, 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 Biotherapeutics leverages state-of-the-art and tissue-customized LNP technologies to target both liver and non-liver cancers. When delivered to tumors through either systemic or local administrations, AP-01 diffuses into tumors through the enhanced permeability and retention effect, which is then internalized by invasive cancer cells followed by the release of the siRNA, thereby inhibiting the expression of MIR-01 and invadopodial formation (Figures 1-2). 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 3-6). 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 7-9). 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.  The mechanisms of action of the AP-01 cancer siRNA nanotherapy

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

IV: intravenous; IT: intratumoral; IP: intraperitoneal; EPR: enhanced permeability and retention

Figure 3.  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 4.  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 5.  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 6.  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 7.  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 8.  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 9.  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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