Syn­er­gis­tic Nan­otech­nol­o­gy for Tar­get­ed Ther­a­peu­tics in Oncology

Biotech­na SA is an inno­v­a­tive biotech­nol­o­gy com­pa­ny ded­i­cat­ed to address­ing unmet med­ical needs in oncol­o­gy through the devel­op­ment of tar­get­ed ther­a­pies for sol­id tumors. Our pro­pri­etary approach lever­ages nan­otech­nol­o­gy plat­forms capa­ble of deliv­er­ing high­ly spe­cif­ic, syn­er­gis­tic com­bi­na­tions of active phar­ma­ceu­ti­cal ingre­di­ents, includ­ing small mol­e­cules and small inter­fer­ing RNA (siR­NA), direct­ly to the tumor microen­vi­ron­ment. By opti­miz­ing the physic­o­chem­i­cal prop­er­ties of these deliv­ery sys­tems, we aim to improve cel­lu­lar uptake, over­come adap­tive chemore­sis­tance, and reduce off-tar­get tox­i­c­i­ties com­pared to tra­di­tion­al therapies.

Our inves­ti­ga­tion­al pro­gram for Triple-Neg­a­tive Breast Can­cer (TNBC) uti­lizes a nov­el nanocar­ri­er con­ju­gate deliv­er­ing a syn­er­gis­tic com­bi­na­tion of two active sub­stances. In xenograft mod­els, it demon­strates a four-fold increase in the Max­i­mum Tol­er­at­ed Dose (MTD) com­pared to the free drug com­bi­na­tion with­out induc­tion of intrin­sic immune acti­va­tion. Fur­ther­more, this tar­get­ed deliv­ery trans­lat­ed to sig­nif­i­cant pri­ma­ry tumor shrink­age and anti-metasta­t­ic activ­i­ty, achieved using a reduced, low­er dose-den­si­ty sched­ule (every-oth­er-week ver­sus weekly).

In addi­tion to our TNBC research, our pre­clin­i­cal pipeline fea­tures a nov­el small-mol­e­cule nanopar­ti­cle for­mu­la­tion for Non-Small Cell Lung Can­cer (NSCLC). High-through­put syn­er­gy screen­ing has iden­ti­fied active com­pound com­bi­na­tions that exhib­it strong in vit­ro syn­er­gism, dras­ti­cal­ly reduc­ing the IC50 to the mid-nanomo­lar range com­pared to micro­mo­lar con­cen­tra­tions for the indi­vid­ual ther­a­peu­tic agents. Con­cur­rent­ly, we are advanc­ing a lipid nanopar­ti­cle plat­form designed to deliv­er siR­NA to sol­id tumors char­ac­ter­ized by spe­cif­ic genet­ic alter­ations. Proof-of-con­cept stud­ies demon­strate that these nanocar­ri­ers achieve robust tar­get gene silenc­ing at both the mRNA and pro­tein lev­els in vivo.

Acknowl­edge­ments

The described research was co-fund­ed under the Smart Growth Oper­a­tional Pro­gramme for 2014 – 2020, Sub-Mea­sure 1.1.1, project „BS2020 – Research and devel­op­ment of a new med­i­c­i­nal prod­uct for the treat­ment of can­cer” (ID: POIR.01.01.01 – 00-0947/20).

Biotech­na SA is an inno­v­a­tive biotech­nol­o­gy com­pa­ny ded­i­cat­ed to address­ing unmet med­ical needs in oncol­o­gy through the devel­op­ment of tar­get­ed ther­a­pies for sol­id tumors. Our pro­pri­etary approach lever­ages nan­otech­nol­o­gy plat­forms capa­ble of deliv­er­ing high­ly spe­cif­ic, syn­er­gis­tic com­bi­na­tions of active phar­ma­ceu­ti­cal ingre­di­ents, includ­ing small mol­e­cules and small inter­fer­ing RNA (siR­NA), direct­ly to the tumor microen­vi­ron­ment. By opti­miz­ing the physic­o­chem­i­cal prop­er­ties of these deliv­ery sys­tems, we aim to improve cel­lu­lar uptake, over­come adap­tive chemore­sis­tance, and reduce off-tar­get tox­i­c­i­ties com­pared to tra­di­tion­al therapies.

Our inves­ti­ga­tion­al pro­gram for Triple-Neg­a­tive Breast Can­cer (TNBC) uti­lizes a nov­el nanocar­ri­er con­ju­gate deliv­er­ing a syn­er­gis­tic com­bi­na­tion of two active sub­stances. In xenograft mod­els, it demon­strates a four-fold increase in the Max­i­mum Tol­er­at­ed Dose (MTD) com­pared to the free drug com­bi­na­tion with­out induc­tion of intrin­sic immune acti­va­tion. Fur­ther­more, this tar­get­ed deliv­ery trans­lat­ed to sig­nif­i­cant pri­ma­ry tumor shrink­age and anti-metasta­t­ic activ­i­ty, achieved using a reduced, low­er dose-den­si­ty sched­ule (every-oth­er-week ver­sus weekly).

In addi­tion to our TNBC research, our pre­clin­i­cal pipeline fea­tures a nov­el small-mol­e­cule nanopar­ti­cle for­mu­la­tion for Non-Small Cell Lung Can­cer (NSCLC). High-through­put syn­er­gy screen­ing has iden­ti­fied active com­pound com­bi­na­tions that exhib­it strong in vit­ro syn­er­gism, dras­ti­cal­ly reduc­ing the IC50 to the mid-nanomo­lar range com­pared to micro­mo­lar con­cen­tra­tions for the indi­vid­ual ther­a­peu­tic agents. Con­cur­rent­ly, we are advanc­ing a lipid nanopar­ti­cle plat­form designed to deliv­er siR­NA to sol­id tumors char­ac­ter­ized by spe­cif­ic genet­ic alter­ations. Proof-of-con­cept stud­ies demon­strate that these nanocar­ri­ers achieve robust tar­get gene silenc­ing at both the mRNA and pro­tein lev­els in vivo.

Acknowl­edge­ments

The described research was co-fund­ed under the Smart Growth Oper­a­tional Pro­gramme for 2014 – 2020, Sub-Mea­sure 1.1.1, project „BS2020 – Research and devel­op­ment of a new med­i­c­i­nal prod­uct for the treat­ment of can­cer” (ID: POIR.01.01.01 – 00-0947/20).

Artur Wnorows­ki

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Artur Wnorowski
Artur Wnorows­ki, Biotech­na, POLAND

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