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GTB-3550 TriKE™ safely activates and delivers IL-15 to NK ...

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GTB-3550 TriKE™ safely activates and delivers IL-15 to NK cells, but not T cells, in immune suppressed patients with advanced myeloid malignancies, a novel paradigm exportable to solid tumors expressing HER2 or B7H3
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GTB-3550 TriKE™ safely activates and delivers IL-15 to NK cells, but not T cells, in immune suppressed patients with advanced myeloid

malignancies, a novel paradigm exportable to solid tumors expressing HER2 or B7H3

GT BioPharma ◦ SAB, Research Support, Consulting, Stock options

Fate Therapeutics◦ Research Support, Consulting, Stock options

OnkImmune, Nektar◦ SAB

Vycellix◦ Consulting, Stock options

Disclosures

CD3/CD19-depletionOvernight IL-2 or IL-15

NK-enriched product

Cy 60 mg/kg x 2Flu 25 mg/m2 x 5

Relapsed/refractory AML

Surge IL-15

PBApheresis

1Miller et al, Blood, 2005; 2Bachanova et al, Blood 2014; 3Cooley et al, Blood Advances 2019

Allogenic NK Cell Adoptive Transfer:Two Decades and Hundreds of Patients

CD3/CD19-depletionOvernight IL-2 or IL-15

NK-enriched product

Cy 60 mg/kg x 2Flu 25 mg/m2 x 5

Relapsed/refractory AML

Surge IL-15

PBApheresis

1Miller et al, Blood, 2005; 2Bachanova et al, Blood 2014; 3Cooley et al, Blood Advances 2019

Allogenic NK Cell Adoptive Transfer:Two Decades and Hundreds of Patients

Lessons learned: More specificity is needed

TriKE

VHH

VH VL

αCD16

αCD33

IL-15

Efficient

Replacement Of scFv With Camelid VHH Single Domain Sequences

camTriKE better activates NK Cells but not T Cells

2nd Generation TriKE Function In Vivo

Click to edit Master title styleCam16/IL15/scFv HER2 TriKE Highly Effective Against Ovarian Cancer

Click to edit Master title stylecam1615camB7H3 TriKE Pan Solid Tumor Targeting

His tag

PE

B7H3+

Tumor

Percent CD107a+ NK Cells

Treatment Condition

Perc

ent N

K C

ells

NK only

NK+WT

NK+KO

NK WT 3n

M IL-15

NK KO 3nM IL

-15

NK WT 3n

M TriKe

NK KO 3nM TriK

E0

20

40

60

80

*

Percent IFN-gamma+ NK Cells

Treatment Condition

Perc

ent N

K C

ells

NK only

NK+WT

NK+KO

NK WT 3n

M IL-15

NK KO 3nM IL

-15

NK WT 3n

M TriKe

NK KO 3nM TriK

E0

10

20

30

40*

IncuCyte-based killing assay. 20,000OVCAR8-GFP cells were allowed toform a spheroid over 3 days, and then40,000 NK were added alone or withB7H3 TriKE.

cam camIL15

Team ScienceUniversity of Minnesota

LaboratoryMartin FelicesDaniel ValleraFrank CichockiNick ZorkoBruce WalcheckAimee MerinoBin ZhangTodd LenvikZachary DavisPippa KennedyUpasana ArvindaEmily ChiuJake Myers

GMP FacilityDavid McKenna, MDDarin SumstadDiane KadidloWilliam SharkeyAndy Sicheneder

Faculty/MDsMark JuckettDaniel J WeisdorfJohn WagnerBruce BlazarClaudio BrunsteinVeronika BachanovaMelissa GellerJoseph Maakaron


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