Skip to main content

Selective Elimination of Senescent Cells (SnCs):  ApoptiCIDe-CE-GERO™

Phoenix’s ApoptiCIDe-CE-GERO™ Technology Leverages Validated Senolytic Technology to De-Risk Our Therapeutic Platform

  • In 2011, Baker et al** demonstrated proof-of-concept that in a genetic mouse model built using technology owned by Bellicum Pharmaceuticals, Inc. and related to Bellicum’s CaspaCIDe™, periodic and regular removal of SnCs by dimerizer-induced apoptosis led to reversal of the aging phenotype

  • Phoenix SENOLYTIX is developing, in-house, gene therapy technologies to more specifically and efficiently target senescent cells for elimination utilizing an improved, proprietary version of CaspaCIDe™, named ApoptiCIDe™, a direct derivative of the technology used by Baker et al**.

  • SENOTHERAPEUTIX Proposition: True senolytic therapeutics must eliminate ≥ 50% of senescent cells in at least two organs by at least two validated methods for quantifying senescent cells, defined by upregulation of well-known aging-related cell cycle arrest proteins (e.g., p16, p21, SA-β-gal, etc.)​

** https://eossenolytix.com/clearance-of-p16ink4a-positive-senescent-cells-delays-ageing-associated-disorders/

ApoptiCIDe-CE-GERO-002™

ApoptiCIDe-CE-GERO-002™ Eliminates ~ 60% to 70% of SnCs With a Single Dose of Vector in Naturally Aged 75-Week-Old Mice

  • ApoptiCIDe-CE-GERO-002™, carrying the iCasp9 ”suicide” switch, targets SnCs via a proprietary SnC-specific promoter, leading to their elimination following administration of the ApoptiCIDe dimerizer “trigger” molecule, PTC-1202.

  • PTC-1202 is Phoenix’s proprietary injectable formulation of rimiducid, the small molecule activator of the ApoptiCIDe™️ cell elimination switch

  • 2.5E11 vg of ApoptiCIDe-CE-GERO-002™ was injected intraperitoneally (IP) into groups of natuarlly aged 75 week old C57Bl/6 female mice on Day 0.  Group 5a received vector only, but in Group 5b, PTC-1202, the ApoptiCIDe “trigger” was administered weekly for four doses beginning ~ 4 weeks after vector administration.

  • Over ~60 to 70% of splenic SnCs were eliminated in ApoptiCIDe-CE-GERO-002™ + PTC-1202-treated animals compared to animals that did not receive PTC-1202 and to saline treated negative controls. Accordingly, Lamin B1 expression also increased significantly in a dimer-dependent fashion.

  • Following PTC-1202 administration, treated animals steadily lose weight, primarily fat,  as do animals treated with MitoXcel™ Technology.

Selective Elimination of White Adipose Tissue (WAT):  ApoptiCIDe-CE-WAT™

ApoptiCIDe-CE-WAT-001™:  WAT-Specific In Vivo Adipocyte Elimination

  • ApoptiCIDe-CE-WAT-001™️ vector was administered IP as indicated at a dose of 2.5E11 vg on Day 0

  • SMG or PTC-1202 was administered as indicated beginning on Day 16

  • PTC-1202 is Phoenix’s proprietary injectable formulation of rimiducid, the small molecule activator of the ApoptiCIDe™️ cell elimination switch

  • Treatment with ApoptiCIDe-CE-WAT™️ + PTC-1202 led to 14.6% lower weight compared to saline-treated animals and an 8.5% lower weight compared to SMG treated animals.

  • Upon discontinuation, the rebound in body weight gain was greater after SMG withdrawal that after PTC-1202 withdrawal.

ApoptiCIDe-CE-WAT-001™:  WAT-Specific In Vivo Adipocyte Elimination

ApoptiCIDe-CE-WAT-001™ Eliminates More Fat More Quickly Than Semaglutide, While Increasing Lean Mass

  • ApoptiCIDe-CE-WAT-001™, carrying the iCasp9 ”suicide” switch, targets the adipocytes in white adipose tissue, via a proprietary WAT-specific promoter.

  • DEXA scan shows a 55% greater reduction in fat, with a concomitant 4% greater increase in lean mass, in ApoptiCIDe-CE-WAT-001™ + PTC-1202-treated animals compared to the saline-treated group.

  • DEXA scan also showed a 54% greater reduction in fat, with a concomitant 5% greater increase in lean mass, in ApoptiCIDe-CE-WAT-001™ + PTC-1202-treated animals compared to the SMG-treated group

ApoptiCIDe-CE-WAT-001™:  WAT-Specific In Vivo Adipocyte Elimination

ApoptiCIDe-CE-WAT-001™ Eliminates White Adipose Tissue (WAT), While Avoiding Brown Adipose Tissue (BAT)

  • ApoptiCIDe-CE-WAT-001™, carrying the iCasp9 ”suicide” switch, targets the adipocytes in white adipose tissue, via a proprietary WAT-specific promoter, leading to their elimination following administration of ApoptiCIDe dimerizer “trigger” molecule, PTC-1202.

  • Expression appears to be limited to WAT over BAT.

  • In ex-vivo harvested inguinal adipose tissue (IAT), there was a PTC-1202-dependent ~35% decrease in BLI in the ex vivo IAT in animals that received PTC-1202 as compared to those that didn’t.