MiNK Presentation SITC 2021

PERSISTENCE AND TISSUE DISTRIBUTION OF AGENT-797

a native allogeneic iNKT cell therapy

Marco A. Purbhoo, Burcu Yigit, Darrian Moskowitz, Ayat Alsaraby, Maurice Kirby, Anitha Swarna, Valeriia Nasonenko, Ilya Mishchenko, Sonia De Munari, Waldo Ortuzar, Koen Van Besien, Don Stevens, Terese Hammond, Xavier Michelet, Marc van Dijk

November 12, 2021

Novel iNKT Cell Therapy, AgenT-797, Demonstrates 77% Survival in Phase 1 Study to Treat Intubated ARDS COVID-19 Patients at SITC

Single infusion of agenT-797 demonstrated a pronounced survival rate of 77% in mechanically ventilated elderly COVID-19 patients with moderate to severe ARDS. 13 patients have been treated to date, with 8 patients discharged and 2 patients ongoing. This represents an improvement compared to a National average of approximately 40 % (range 24-53%) for intubated or mechanically ventilated patients during time of enrollment.

77% overall survival in intubated ICU Patients with ARDS (COVID-19)

Dose Level

Agent-797

(No. cells)

No. Patients

No. Discharged

No. Deaths

1

100 x 106

3

2

1

2

300 x 106

4

3

1

3

1000 x 106

6

3

1

Phase 1 study to evaluate the safety and efficacy of agenT-797, an unmodified, allogeneic iNKT cell therapy, in patients with acute respiratory distress syndrome (ARDS) secondary to COVID-19, requiring mechanical ventilation

Dose Level 1

Agent-727(No. cells): 100 x 1016

No. Patients: 3

No. ongoing: ---

No. discharged: 2

No. deaths: 1

Dose Level 2

Agent-727(No. cells): 300 x 1016

No. Patients: 4

No. ongoing: ---

No. discharged: 3

No. deaths: 1

Dose Level 3

Agent-727(No. cells): 1000 x 1016

No. Patients: 6

No. ongoing: ---

No. discharged: 4

No. deaths: 1

Phase 1 study to evaluate the safety and efficacy of agenT-797, an unmodified, allogeneic iNKT cell therapy, in patients with acute respiratory distress syndrome (ARDS) secondary to COVID-19, requiring mechanical ventilation.

AgenT-797 can be administered tolerably up to 1000 x 106 cells/dose without neurotoxicity or cytokine release syndrome

6 patients have been treated at the maximal dose level and no dose limited toxicities have been observed. These patients are heavily pre-treated with a median age of 69 (49-77).

Baseline Demographics

Characteristic

All Patients

(n=13)

Media Age Range

69 (49-77)

Sex, n (%)

Male

3 (23)

Female

10 (77)

Co-medications, n

Remdesivir
Steroids

5

Remdesivir
Steroids
Tocilizumab

5

Other

3

Initial data translational data confirmed the trafficking ability of these tissue resident cells, showing the translocation of iNKTs

MiNK developed a digital PCR-based method to characterize agent-797 in patients; analyses of tissue distribution, persistence, and functional capacity of agent-797 are underway.

Key observations:

  • Initial spike of agent-797 cells in peripheral blood observed post-infusion
  • Detection of agent-797 in peripheral blood up to day 6 of treatment
  • Detected level scales with dose level
  • Data consistent with the expected rapid translocation of iNKT cells from blood into tissue
  • Method can be validated for any tissue

About MiNK iNKTs

iNKTs are Designed to Address Immunity to Cancer & Beyond

Invariant Natural Killer T (iNKT) cells are key effectors and regulators of immune responses, making them an ideal immunotherapy.

In cancer, iNKT cells reshape the tumor microenvironment:

  • Promotepolarizationoftumor-associatedmacrophagestoaM1phenotype
  • Deplete tumor-associated neutrophils
  • Reduce activity of myeloid-derived suppressor cells (MSDCs)
  • Induce maturation of immature Dendritic cells(DCs)
  • Induce an IL-12 mediated positive feedback loop which boosts the activity of other tumor-resident immune effector cells, including T cells and NK cells

In viral lung disease, iNKT cells:

  • Induce maturation of immature DCs
  • Recruit NK cells and cytotoxic T cells
  • Control secondary bacterial outgrowth through cytokine secretion
  • Reduce activity of myeloid-derived suppressor cells
  • Kill inflammatory monocytes
  • Protect airway epithelial cells from damage

MiNK’s iNKT cell manufacturing is scalable

  • iNKT cells can be manufactured from healthy donors
  • Scaling up for in-house production of >10.000 doses / year.
  • MiNK Therapeutics’ iNKT cells (agent-797) are off-the-shelf, scalable, and efficiently transported and stored