IN8bio : ISCT 2026 Poster final

Published: 2026-05-14 08:16:14 ET INAB

Published on 05/14/2026 at 08:16 am EDT

Mariska A. ter Haak1, Catherine P. Langford1, Gulpreet Kaur2, James Perna2, Jason L. Weirather2, Lawrence Lamb1, Kate M. Rochlin1 1 IN8bio, Inc., New York, NY, United States, 2Elucidate Bio, Inc., Medford, MA, United States,

GBM: High Unmet Clinical Need

DeltEx DRI treatment induces T cell and reduces granulocyte infiltration

Glioblastoma (GBM) is one of the most aggressive cancers with median overall survival (mOS) of only ~12 months(m) and no drug approvals or change to standard-of-care (SOC) in 20+ years. GBM clinical trials face difficult/poor brain imaging and an inability to repeat biopsy. Due to the paucity of treatments, patients undergo limited biomarker stratification with almost all receiving SOC despite biological heterogeneity.

Recent data from INB-200/400 Phase 1/2 trial of DeltExTM Drug Resistant Immunotherapy (DeltEx DRI), demonstrated durable survival improvements in newly diagnosed GBM. DeltEx DRI uses autologous MGMT-modified γδ T cells engineered for temozolomide (TMZ) resistance, enabling intrathecal dosing concomitantly with TMZ.

Surgical resection followed by apheresis

Unmethylated Paired Patient a DeltEx DRI

Percent cellularity

(initial) (recurrent)

CD3 CD8

EGFR Ki67 CD31

EGFR

Podoplanin CD31

4c Patient a Initial

Patient a Recurrent

Cell type Composition

Patient b (SOC)

Patient a (DeltEx DRI)

6 weeks induction TMZ + radiation

Patient a Initial

Patient a Recurrent

Patient b Initial

Patient b Recurrent

9.4%

1.7%

2.1%

Ki-67+ as % of Glioma-like cells

14 13.4%

6 cycles maintenance TMZ + DRI

Granulocytes (subtypes)

Figure 1 DeltEx DRI Treatment Regimen & Timing

MultiDose DeltEx DRI (n=14)

SOC (n=10)

Improvement

Median PFS

13.0m

6.6m

+97%

Median OS

17.2m+

13.2m

≥+30.3%

Table I Median Progression Free Survival (PFS) and Overall Survival (OS) for GBM patients either treated with Standard of Care (SOC) only or concomitantly with Multidose DeltEx DRI dose levels.

Patient a Initial

Patient a Recurrent

Patient b Initial

Patient b Recurrent

Methods: IN8bio Clinical Samples & Elucidate' s Platform

To explore mechanisms underlying tumor response, we initiated a pilot study using paired

Figure 4 Tumor microenvironment remodeling across treatment arms. (a) In Patient a (DeltEx DRI), the tumor microenvironment shifted from cold to hot, marked by increased T cell infiltration, suppression of proliferation (reduced Ki-67), and signs of immune escape (increased podoplanin). (b) Ki-67+ Glioma-like cells decreased from 9.4% to 1.7% at re-resection in Patient a (DeltEx DRI), an 82% reduction in tumor proliferative fraction. In Patient b (SOC), Ki-67+ Glioma-like cells decreased from 13.4% to 2.1%, an 84% reduction. (c) Spatially-resolved single-cell phenotype plots at initial and recurrent resection for Patient a, with cell type composition overview for Patients a and b. (d) Fold change between initial and recurrent samples shows T cell infiltration across both treatment arms; however, a marked drop in granulocytes, further specified by subtype, was observed only in the DeltEx DRI patient, potentially driven by γδ T cell-mediated clearance. Mesenchymal-like tumor/stromal expansion was also noted, suggesting progressive tumor evasion.

biopsies at diagnosis and relapse from one SOC patient and one DeltEx DRI multidose patient who, despite exceeding predicted mPFS, showed one of the poorest PFS and OS within the treatment group: an informative outlier for understanding treatment response heterogeneity.

Diagnostic biopsies from GBM patients with methylated and unmethylated MGMT promoter status were also included for baseline tumor analysis.

Study Design Overview

Research

Questions

1. At Diagnosis, are there differences

in tumor environment between GBM Methylated or Unmethylated?

2. How does the tumor environment 3. Do Untreated tumors exhibit change from Diagnosis vs Relapse? different profiles vs Treated tumors?

GBM Unmethylated

GBM Methylated

Patient a

(DeltEx DRI)

Patient b

(SOC)

Meth vs Unmeth

Patient c

(DeltEx DRI)

Patient d

(DeltEX DRI)

Primary vs

Recurrent

[email protected] [email protected]

Patient a

(DeltEx DRI)

Patient b

(SOC)

No Sample

Treated

Untreated

1600

1400

1200

1000

800

600

400

200

CD8+ T cells Glioma-like Granulocytes M2

Macrophages

Tregs

5b 80

PD1+ % CD8+

(exhaustion)

GranzymeB+

% CD8+

CD8+ % T cells Treg % T cells

CD8+ T cells

Tumor burden

Ki-67 (tumor)

Granulocytes

M2 Macrophages

Tregs % T cells

18×

−24%

−82%

−90%

+4×

+2.4×

7.2 → 128.6 /mm²

Glioma density

9.4% → 1.7%

645 → 65 /mm²

164 → 663 /mm²

1.9% → 4.6%

PD1+ = exhaustion marker · GranzymeB+ = cytotoxic activity ·

Relapse

(Recurrent Tumor)

Diagnosis

(Initial Tumor)

Figure 5 DeltEx DRI influences the GBM tumor microenvironment at the cellular level which is visible at recurrence. Cell type density (cells/mm²) is normalized to tissue area to account for differences in section size between samples. (a) CD8+ T cell density increased 18-fold post-treatment (7.2 → 128.6 cells/mm²), consistent with robust intratumoral T cell infiltration. Ki-67+ Glioma-like cell fraction decreased 82% (9.4% → 1.7%), indicating marked suppression of tumor proliferation. CD163+ myeloid cell density increased 4-fold (164 → 663 cells/mm²), reflecting M2 macrophage expansion and a potentially compensatory immunosuppressive tumor response. Granulocyte density decreased 90% (645 → 65 cells/mm²). (b) PD1+ CD8+ T cells decreased from 14.8% to 8.0%, indicating reduced T cell exhaustion. GranzymeB+ cytotoxic CD8+ T cells increased 3.2-fold (3.9% → 12.4%), while Regulatory T cells expanded 2.4-fold (1.9% → 4.6%), reflecting a net gain in cytotoxic capacity over suppressive pressure, consistent with a functionally active anti-tumor immune response.

(AI Pathologist)

Methylated GBM exhibit more cytotoxic CD8 T cells & appear less exhausted

Figure 2: (a) Study design and sample selection. (b) FFPE tissue sections (5-7 µm) underwent high-plex spatial proteomics (>50 immuno-oncology markers) and transcriptomics (Visium HD) to compare tumor and adjacent healthy brain tissue, from sample preparation through final tumor mapping.

Figure 6 TRDC and TRGC1 expression across spatial neighborhoods. (a) γδ T cell marker levels detected across neighborhood clusters; NGS depth was insufficient for meaningful quantitative distinction but informative for localizing γδ T cell infiltration. (b) Spatially-resolved single-cell phenotype plots of neighborhood clusters.

Transcriptomics reveal a shift toward M2-like tumor invasion

Patient a

Initial

Patient a

Recurrent

Patient a

Initial

Patient a

Recurrent

Patient a Initial

Patient a Recurrent

Neighbothood% Neighborhood %

Pathway Ligand Glioma MES-like CD163+ CD163−

Marker CD163+ CD163−

TAM / M2 program

LYVE1 +4.58 +0.86

STAB1 +4.34 +2.86

MERTK +1.75 +4.13

CD163 +1.80 +3.22

MARCO +2.46 +2.73

MAF +1.39 +0.35

MRC1 +1.24 +1.27

TGFB1 -2.27 +1.85

M1 antitumor effector

CXCL9 -3.05 absent

CXCL10 -1.21 +0.85

CXCL11 -1.05 absent

IL12B -2.46 absent

Increases in Patient a Recurrent

PD-L1 / PD-1 CD274 +3.90 +1.11

Gal-9 / TIM-3 LGALS9 +1.99 +0.14 +0.70 absent

Gal-3 / LAG-3 LGALS3 -0.03 +0.20 +0.68

B7-H4 VTCN1

VISTA VSIR +0.56 +0.48 +1.06

TGFβ TGFB2 +0.09 +1.17 +0.99 absent

Decreases in Patient a Recurrent

Gal-1 LGALS1

B7-H3 CD276 -1.15

TIGIT PVR -0.19

TIGIT NECTIN2 -0.72 -1.19 -0.43 +0.06

Ligand expression across tumor and myeloid bins, log₂ FC (CPM, Re-resect / Initial). Dot size = |log₂ FC|. Blue = up, red = down, gray = flat or absent.

Both bins shift TAM · CD163, MERTK, MARCO, STAB1 up across both

Protein CD163+/− erodes · CD163− bin

acquires CD163, TGFB1 transcript

No M1 effector output · CXCL9/10/11, IL12B absent or decreasing

Figure 7 Glioblastoma cells under DeltEx therapy mount a coordinated transcriptional immune evasion response (a)

Under γδ T cell-mediated cytotoxic pressure, glioma-like tumor cells upregulate checkpoint ligands CD274 (PD-L1; +14×), LGALS9 (Galectin-9; +4×), and PDCD1LG2 (PD-L2; +3×), alongside CXCL12-mediated T cell exclusion and IL-10 secretion. Concurrently,

Methylated

Ki-67+ %

Glioma-like

15.4

Cytotoxic activity

GranzymeB+ % CD8+ T cells

57.4

proliferative (MKI67; −8×) and stemness (SOX2, NES, NOTCH1) gene expression are markedly suppressed, suggesting the tumor

8.0

15 13.4

60 51.3

trades proliferative capacity for immune escape under cytotoxic selection pressure. (b) The DeltEx DRI-treated patient shows a shift

9.4

Patient b

Patient d

20 3.9

41.8

toward an inhibitory TAM phenotype, with increased M2-like and decreased M1-like polarization.

Conclusions

Patient Patient Patient Patient Patient Patient Patient Patient

a b c d a b c d

UNMETH METH UNMETH METH

Exhaustion status

PD1+ % CD8+ T

cells

14.8

9.8

8.4

5.4

Patient a

Patient c

Patient Patient Patient Patient

Macrophage polarization

CD163+ M2-like

% phagocytic myeloid

80 62.0

42.3

28.3

15.3

Patient Patient Patient Patient

DeltEx DRI shows promise in extending mPFS and mOS in patients

Deeper analysis furthers understanding of the tumor microenvironment, response & DeltEx DRI effects

Enables biomarker discovery in future DeltEx DRI pivotal studies

UNMETH METH UNMETH METH

Figure 3 Baseline immune functional state stratified by MGMT methylation status across four initial resection samples (a) Spatially-resolved single-cell phenotype plot from multiplex immunofluorescence (mIF), where each dot represents a cell plotted at its true x/y coordinate, colored by assigned cell type. (b) No consistent separation by methylation status was observed for tumor proliferation (Ki-67+: 9.4-13.4% unmethylated vs. 8.0-15.4% methylated). Cytotoxic activity was directionally higher in methylated samples (GranzymeB+: 51.3% and 57.4%) vs. unmethylated (3.9% and 41.8%), with Patient a representing an outlier of particularly low cytotoxic capacity. Methylated samples showed lower T cell exhaustion (PD1+: 8.4% and 5.4% vs. 14.8% and 9.8%) and lower M2 macrophage polarization (28.3% and 15.3% vs. 42.3% and 62.0%), suggesting a more immunologically permissive baseline microenvironment in MGMT-methylated tumors. Data are descriptive; n=2 per group.

May inform patient stratification for novel GBM therapies, which is currently very limited

Platform enables future investigation into differential DeltEx DRI response, with early observations suggesting differences in immune escape and baseline tumor aggressiveness

Presented in ISCT 2026 Annual Meeting, Dublin, Ireland, 2026MAY05-09

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IN8BIO Inc. published this content on May 14, 2026, and is solely responsible for the information contained herein. Distributed via Public Technologies (PUBT), unedited and unaltered, on May 14, 2026 at 12:15 UTC.