GENETIC REPROGRAMMING OF TAMS BY ENGINEERED EXOSOMES RESULTS IN POTENT SINGLE AGENT ANTI-TUMOR ACTIVITY Sushrut Kamerkar 1 , Dalia Burzyn 1 , Charan Leng 1 , Olga Burenkova 1 , Su Chul Jang 1 , Raymond Yang 1 , Katherin Kirwin 1 , Tong Zi 1 , William Dahlberg 1 , Eric Zhang 1 , Scott Estes 1 , Sylvie Maubant 2 , Olivier Duchamp 2 , Kyriakos Economides 1 , Timothy Soos 1 , Sriram Sathyanarayanan 1 . 1. Codiak BioSciences, Cambridge, MA. 2. Oncodesign, Dijon, France Codiak Proprietary Information – Not for Further Dissemination or Use AACR ANNUAL MEETING JUNE 23, 2020
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GENETIC REPROGRAMMING OF TAMS BY ENGINEERED … · GENETIC REPROGRAMMING OF TAMS BY ENGINEERED EXOSOMES RESULTS IN POTENT SINGLE AGENT ANTI-TUMOR ACTIVITY Sushrut Kamerkar1, Dalia
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GENETIC REPROGRAMMING OF TAMS BY ENGINEERED EXOSOMES RESULTS IN POTENT SINGLE AGENT ANTI-TUMOR ACTIVITY Sushrut Kamerkar1, Dalia Burzyn1, Charan Leng1, Olga Burenkova1, Su Chul Jang1, Raymond Yang1, Katherin Kirwin1, Tong Zi1, William Dahlberg1, Eric Zhang1, Scott Estes1, Sylvie Maubant2, Olivier Duchamp2, Kyriakos Economides1, Timothy Soos1, Sriram Sathyanarayanan1.
1. Codiak BioSciences, Cambridge, MA.2. Oncodesign, Dijon, France
Codiak Proprietary Information – Not for Further Dissemination or Use
AACR ANNUAL MEETINGJUNE 23, 2020
2Codiak Proprietary Information – Not for Further Dissemination or Use
Disclosure Information
AACR Annual Meeting 2020
Dalia Burzyn
• I have the following financial relationships to disclose:- Employee of Codiak BioSciences
• I will not discuss off label use and/or investigational use in my presentation
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M2-like tumor-associated macrophages (TAMs) promote cancer progression
Codiak Proprietary Information – Not for Further Dissemination or Use
Jackute et al. BMC Immunology 19:3, 2018
Total M2 macrophage density correlation to overall survival in lung cancer
Anfray et al. Cells, 9, 46, 2020
Reprogramming TAMs by targeting key “undruggable” pathways
4Codiak Proprietary Information – Not for Further Dissemination or Use
exoASO-STAT6 or C/EBPb
Ø Selective modulation of key M2 transcription factors by combining:
Ø Preferential tropism of exosomes to myeloid cells
Ø Codiak’s exoASO™ platform to load exosomes with specific antisense oligonucleotides (ASOs)
exosomeSTAT6 or C/EBPb antisense oligonucleotide
TAM reprogramming
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0 6 12 18 24 30 36 42 480
5×107
1×108
1.5×108
Time (Hours)
Tota
l Obj
ect I
nten
sity
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Exo-ASO-M2
Free-ASO-M2
Exo-ASO M0
Free ASO-M0
Exosome-mediated selective uptake in human M2 macrophages
exoASO shows enhanced tropism to M2 macrophages in vitro
Ø Exosome surface protein PTGRFN may mediate selective delivery to macrophages and other myeloid cells via the cell type specific expression of its cognate receptors in these cells
PTGFRN cognate receptors in human GBMM2 mac + exoASO
M2 mac + Free ASO
In vivo exosome-mediated selective delivery of ASOs to macrophages and MDSCs