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MiNK Presentation SITC 2021

AGENT-797, A NATIVE ALLOGENEIC "OFF-THE-SHELF" iNKT CELL THERAPY SHOWS ANTI-TUMOR ACTIVITY

Burcu Yigit, Darrian Moskowitz, Xavier Michelet, Antoine Tanne, Marc van Dijk

November 12, 2021

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About iNKTs

iNKT trafficking, homing, and functional characteristics underscore data from MiNK’s ongoing clinical trial in relapsed refractory multiple myeloma

MiNK has initiated studies of agenT-797 for the treatment of patients with relapsed/refractory multiple myeloma and solid tumor cancers.

Early data of single dose administration of AgenT-797 without lymphodepletion in a heavily pre-treated multiple myeloma population refractory to anti-BCMA therapy revealed suppression of M spike protein, tumor cells in the bone marrow, and durable disease stabilization for over 6 months.

New pre-clinical data demonstrated the persistence, trafficking, and anti-tumor activity of MiNK’s allogeneic iNKT cell therapy, agenT-797, in solid and liquid malignancies

MiNK established a xenograft model for the study of agenT-797 to recapitulate human iNKT cell distribution and evaluate efficacy in tumor models. iNKT cells were shown to infiltrate the tumor where they became activated and proliferated over time.

agenT-797 cells are active in vivo in a melanoma solid tumor model A375

A. In the subcutaneous model of A375- CD1d, upon injection of iNKT cells, cells infiltrated their natural homing site, bone marrow, whereas some of the iNKT cells made it in the tumor. Over time, iNKT cells residing in blood and bone marrow of mice did not expand, whereas the iNKT cells in the tumors expanded over time.
B. Only the iNKT cells that reached the tumor became activated in response to their environment but not the cells in the blood or bone marrow.
C. Whereas the iNKT cells in the blood or bone marrow cannot maintain their proliferative capacity, proliferation of iNKTs in the tumor increases (Representative plots from tumor samples)

agenT-797 cells are reaching tumor sites and are functional rapidly post infusion

iNKTs demonstrated potent tumor killing activity and cytotoxic effects in solid and liquid malignancies. An overall reduction in tumor size was seen with iNKT injection compared to the control group, demonstrating the impact of iNKT cells on tumor growth.

Activation (CD69+CD25+) and proliferation (Ki-67+) levels of iNKT cells were measured from bone marrow, spleen and blood of mice on days 8 and 13. In comparison to the activation levels of iNKT cells before injection, iNKT cells that reached the tumor sites became rapidly activated upon tumor encounter and increased proliferation was observed.
Upon activation, iNKT cells started producing Th1 cytokines IFN-g, and TNF-a.

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