PIPELINES

 

AP-01

AP-01 is a 3rd-generation lipid nanoparticle (3gLNP)-formulated siRNA mixture that target a cancer-specific transcript of the gene encoding MIR-01, a key regulator of invadopodia biogenesis and oncogenic signaling in invasive cancer cells. AP-01 is designed to simultaneously block the invasive growth and the distant metastasis of advanced cancers. Antapodia Therapeutics combines the market's most advanced 3gLNP and liver-blocking 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 (EPR) effect, which is then internalized by invasive cancer cells followed by the release of the siRNA, thereby inhibiting MIR-01 expression, invadopodial formation, and cancer cell invasiveness (Figures 1-3). The company has completed more than 10 compelling proof-of-concept studies showing that intravenous (IV) AP-01 therapy dramatically shrinks primary tumors and simultaneously abolishes distant metastasis, thereby lengthening survival in preclinical models of breast, pancreatic, and lung cancer metastasis (Figures 4-6). In combination with a proprietary liver-blocking liposome, IV AP-01 therapy not only inhibits metastasis but also shrinks primary breast cancer (Figures 7). Aside from systemic therapy, intratumoral (IT) injections of AP-01 can induce the complete remission of primary liver and breast cancers, wherein loco-regional therapies are clinically applicable (Figures 8-10). The company is now testing AP-01 in clinically relevant PDX tumor metastasis models and optimizing its dosing schedule to substantiate its anti-tumor efficacy and survival-lengthening effect further.

Figure 1.  The mechanisms of action of AP-01

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 2. AP-01 inhibits MIR-01 expression, invadopodia formation, and cancer cell invasion

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

LNP, lipid nanoparticle; IC50, 50% inhibitory concentration. Invadopodia are marked by cortaction+F-actin+ puncta.

Figure 3. Systemic AP-01 therapy effectively delivers siRNA to tumor cells to reduce MIR-01 expression

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

TNBC: triple-negative breast cancer; IV: intravenous; IB, immunoblotting; LNP, lipid nanoparticle.

Figure 4.  Systemic AP-01 therapy inhibits breast cancer metastasis and lengthens survival

Metastasis control: 88.9%; survival extension 94.4%

Figure 4.  Systemic administration of AP-01 attenuates PDAC metastasis and lengthens survival(metastasis control rate = 79.4%; survival extension = 28%).

TNBC: triple-negative breast cancer; IV: intravenous; BLI: bioluminescence.

Figure 5.  Systemic AP-01 therapy inhibits pancreatic cancer metastasis and lengthens survival

Metastasis control: 79.4%; survival extension 33.3%

Figure 5.  Systemic administration of AP-01 abolishes breast cancer metastasis.

PDAC: pancreatic ductal adenocarcinoma; IV: intravenous; BLI: bioluminescence.

Figure 6.  Systemic AP-01 therapy inhibits lung cancer dissemination and lengthens survival

Metastasis control: 99.7%; survival extension: 41.8%

Figure 6.  Combined local and systemic AP-01 treatment shrinks primary breast cancer and prevents pulmonary metastasis.

NSCLC: non-small cell lung cancer; IV: intravenous; BLI: bioluminescence.

Figure 7.  Systemic AP-01 therapy in conjunction with liver-blocking liposome shrinks primary breast cancer and completely prevents metastasis
Growth inhibition: 84.6%; metastasis control: 100%

Figure 7.  Intratumoral (IT) AP-01 synergizes with Sorafenib in the treatment of HCC.

TNBC: triple-negative breast cancer; IV: intravenous; TGI: tumor growth inhibition; BLI: bioluminescence; MC: metastasis control.

Figure 8.  Combined local and systemic AP-01 therapy shrinks primary breast cancer, prevents metastasis, and doubles the length of survival

Growth inhibition: 92.8% (AP-01 alone); metastasis control: 100% (AP-01 ± paclitaxel)

Survival extension: 108.2% (AP-01 alone)

Figure 8.  Combined local and systemic AP-01 treatment shrinks primary TNBC and prevents pulmonary metastasis (tumor control rate = 92.8%; metastasis control rate = 100%).

TNBC: triple-negative breast cancer; IT: intratumoral; IP: intra-peritoneal; IV: intravenous; BLI: bioluminescence.

Figure 9.  Intratumoral AP-01 therapy synergizes with sorafenib in liver cancer treatment

Growth inhibition: 100% (complete remission; AP-01 2.5 mg/kg)

Figure 9.  Intratumoral (IT) AP-01 synergizes with sorafenib in the treatment of HCC (tumor control rate = 100% [high dose]).

HCC: hepatocellular carcinoma; IT: intratumoral; PO, per os; BLI, bioluminescence

Figure 10.  Systemic AP-01 therapy shrinks primary liver cancer, inhibits daughter nodules, and lengthens survival

Growth inhibition: 57.5%; survival extension: 92.3%

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

HCC, hepatocellular carcinoma; IV: intravenous; BLI, bioluminescence

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Designed by Justin V. Tsai in 2021

Copyright © Antapodia Therapeutics, Inc., WA, USA. All Rights Reserved.

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