5 INCA035784 A Novel T Cell-Redirecting Antibody for mutCALR MPN

Author

Clinical Data Analysis

Published

August 19, 2026

6 Study Overview

This document presents preclinical data for INCA035784, a novel mutCALR×CD3 T cell-redirecting antibody for patients with myeloproliferative neoplasms (MPNs) carrying calreticulin mutations. Presented as oral presentation S212 at the European Hematology Association (EHA) Congress, Milan, Italy, June 12–15, 2025.

Molecule: INCA035784 — fully human, Fc-silenced, IgG1 bispecific antibody targeting mutant calreticulin (mutCALR) N-domain and CD3 on T cells.

Platform: Generated using Fab domains isolated from immunized mice via the Merus proprietary bispecific antibody platform (Merus NV, Utrecht, Netherlands).

Clinical Trial Registration: NCT07008118

Affiliations: Incyte Research Institute (Wilmington, DE, USA); Merus NV (Utrecht, The Netherlands); Oxford University (Oxford, UK)

Code

# Create molecule characteristics data
molecule_data <- data.frame(
  Characteristic = c(
    "Molecule name", "Format", "Fc modification",
    "Target arm 1 (tumor)", "Target arm 2 (effector)",
    "Binding epitope on mutCALR", "Epitope determination method",
    "Relationship to mutCALR antagonist mAb",
    "Binding to wtCALR (stress-induced surface exposure)", 
    "Affected by exogenous soluble CALR",
    "Equipotent across CALR mutation types",
    "Clinical trial"
  ),
  Value = c(
    "INCA035784", "Fully human IgG1 bispecific antibody", "Fc-silenced",
    "Mutant calreticulin (mutCALR) — N-domain", "CD3 (T cells)",
    "N-domain of mutCALR (conserved across all CALR mutation types; unaltered by C-terminal deletions/insertions)",
    "Cryo-electron microscopy (cryo-EM) with 2D classification",
    "Binds a distinct epitope from mutCALR antagonist mAb (INCA33989); cryo-EM shows INCA035784 Fab binds N-domain while antagonist mAb binds near C-domain region",
    "No — does not bind wtCALR even when doxorubicin induces surface translocation (tested in Reh ALL cell line)",
    "No — binding unaffected by exogenous soluble CALR",
    "Yes — equipotent binding, T cell activation, and cytotoxicity against Type 1 and Type 2 mutCALR",
    "NCT07008118"
  )
)

6.1 Table 1: INCA035784 Molecule Characteristics

Code

molecule_data %>%
  gt() %>%
  tab_header(
    title = "INCA035784 Molecule Characteristics",
    subtitle = "mutCALR×CD3 T Cell-Redirecting Antibody"
  ) %>%
  cols_label(
    Characteristic = "Characteristic",
    Value = "Description"
  ) %>%
  tab_style(
    style = cell_text(weight = "bold"),
    locations = cells_column_labels()
  ) %>%
  tab_style(
    style = cell_fill(color = "#f8f9fa"),
    locations = cells_body(rows = seq(2, nrow(molecule_data), 2))
  ) %>%
  tab_style(
    style = cell_fill(color = "#d4edda"),
    locations = cells_body(rows = c(9, 10, 11))
  ) %>%
  tab_footnote(
    footnote = "mutCALR = mutant calreticulin; wtCALR = wild-type calreticulin; TPOR = thrombopoietin receptor; mAb = monoclonal antibody",
    locations = cells_body(columns = Characteristic, rows = 4)
  ) %>%
  tab_footnote(
    footnote = "CALR mutations result in loss of the C-terminal KDEL ER retention signal, causing mutCALR to translocate to the cell surface in complex with TPOR. The N-domain is structurally conserved across Type 1 (deletion), Type 2 (insertion), and other CALR mutation types.",
    locations = cells_body(columns = Characteristic, rows = 6)
  )

Characteristic	Description
INCA035784 Molecule Characteristics
mutCALR×CD3 T Cell-Redirecting Antibody
Molecule name	INCA035784
Format	Fully human IgG1 bispecific antibody
Fc modification	Fc-silenced
Target arm 1 (tumor)¹	Mutant calreticulin (mutCALR) — N-domain
Target arm 2 (effector)	CD3 (T cells)
Binding epitope on mutCALR²	N-domain of mutCALR (conserved across all CALR mutation types; unaltered by C-terminal deletions/insertions)
Epitope determination method	Cryo-electron microscopy (cryo-EM) with 2D classification
Relationship to mutCALR antagonist mAb	Binds a distinct epitope from mutCALR antagonist mAb (INCA33989); cryo-EM shows INCA035784 Fab binds N-domain while antagonist mAb binds near C-domain region
Binding to wtCALR (stress-induced surface exposure)	No — does not bind wtCALR even when doxorubicin induces surface translocation (tested in Reh ALL cell line)
Affected by exogenous soluble CALR	No — binding unaffected by exogenous soluble CALR
Equipotent across CALR mutation types	Yes — equipotent binding, T cell activation, and cytotoxicity against Type 1 and Type 2 mutCALR
Clinical trial	NCT07008118
¹ mutCALR = mutant calreticulin; wtCALR = wild-type calreticulin; TPOR = thrombopoietin receptor; mAb = monoclonal antibody
² CALR mutations result in loss of the C-terminal KDEL ER retention signal, causing mutCALR to translocate to the cell surface in complex with TPOR. The N-domain is structurally conserved across Type 1 (deletion), Type 2 (insertion), and other CALR mutation types.

7 Biological Rationale: Cell Surface Translocation of Mutant CALR

Code

# Create biological rationale data
rationale_data <- data.frame(
  Feature = c(
    "Wild-type CALR (wtCALR)",
    "Mutant CALR (mutCALR) — Type 1/Type 1-like",
    "Mutant CALR (mutCALR) — Type 2/Type 2-like",
    "Mechanism of surface exposure",
    "Therapeutic vulnerability",
    "INCA035784 binding requirement"
  ),
  Description = c(
    "Retains KDEL ER retention signal → remains in endoplasmic reticulum; not accessible on cell surface",
    "C-terminal deletion → loss of KDEL sequence → translocates to cell surface in complex with TPOR",
    "C-terminal insertion → loss of KDEL sequence → translocates to cell surface in complex with TPOR",
    "All pathogenic CALR mutations alter the C-terminus, causing loss of the KDEL ER retention signal. mutCALR then forms a complex with TPOR and is presented on the plasma membrane.",
    "Surface-exposed mutCALR-TPOR complex is a tumor-specific neoantigen accessible to antibody-based therapies",
    "Requires mutCALR in complex with TPOR on cell surface — does not bind intracellular CALR or soluble CALR"
  )
)

7.1 Table 2: Biological Rationale for mutCALR Targeting

Code

rationale_data %>%
  gt() %>%
  tab_header(
    title = "Biological Rationale: mutCALR as a Therapeutic Target",
    subtitle = "Cell Surface Translocation Upon Loss of KDEL ER Retention Signal"
  ) %>%
  cols_label(
    Feature = "Feature",
    Description = "Description"
  ) %>%
  tab_style(
    style = cell_text(weight = "bold"),
    locations = cells_column_labels()
  ) %>%
  tab_style(
    style = cell_fill(color = "#f8d7da"),
    locations = cells_body(rows = 1)
  ) %>%
  tab_style(
    style = cell_fill(color = "#d4edda"),
    locations = cells_body(rows = c(2, 3))
  ) %>%
  tab_style(
    style = cell_fill(color = "#cfe2ff"),
    locations = cells_body(rows = c(4, 5, 6))
  ) %>%
  tab_style(
    style = cell_text(size = px(12)),
    locations = cells_body(columns = Description)
  ) %>%
  cols_width(
    Feature ~ px(200),
    Description ~ px(500)
  ) %>%
  tab_footnote(
    footnote = "KDEL = Lys-Asp-Glu-Leu ER retention signal; TPOR = thrombopoietin receptor; ER = endoplasmic reticulum",
    locations = cells_column_labels(columns = Feature)
  )

Feature¹	Description
Biological Rationale: mutCALR as a Therapeutic Target
Cell Surface Translocation Upon Loss of KDEL ER Retention Signal
Wild-type CALR (wtCALR)	Retains KDEL ER retention signal → remains in endoplasmic reticulum; not accessible on cell surface
Mutant CALR (mutCALR) — Type 1/Type 1-like	C-terminal deletion → loss of KDEL sequence → translocates to cell surface in complex with TPOR
Mutant CALR (mutCALR) — Type 2/Type 2-like	C-terminal insertion → loss of KDEL sequence → translocates to cell surface in complex with TPOR
Mechanism of surface exposure	All pathogenic CALR mutations alter the C-terminus, causing loss of the KDEL ER retention signal. mutCALR then forms a complex with TPOR and is presented on the plasma membrane.
Therapeutic vulnerability	Surface-exposed mutCALR-TPOR complex is a tumor-specific neoantigen accessible to antibody-based therapies
INCA035784 binding requirement	Requires mutCALR in complex with TPOR on cell surface — does not bind intracellular CALR or soluble CALR
¹ KDEL = Lys-Asp-Glu-Leu ER retention signal; TPOR = thrombopoietin receptor; ER = endoplasmic reticulum

8 Structural Analysis: Cryo-EM Epitope Mapping

Code

# Create cryo-EM structural findings
structural_data <- data.frame(
  Finding = c(
    "INCA035784 Fab binding site",
    "mutCALR antagonist mAb binding site",
    "Epitope relationship",
    "2D classification",
    "CALR domain structure"
  ),
  Detail = c(
    "N-domain of mutCALR — conserved region unaffected by C-terminal mutations",
    "Near C-domain region of mutCALR — distinct from INCA035784 epitope",
    "Non-overlapping epitopes — INCA035784 and antagonist mAb bind distinct regions, enabling potential combination",
    "14 nm complex visualized by 2D classification of cryo-EM images",
    "N-domain (INCA035784 target) → P-domain → C-domain (mutated region; antagonist mAb target)"
  )
)

8.1 Table 3: Cryo-EM Structural Findings

Code

structural_data %>%
  gt() %>%
  tab_header(
    title = "Cryo-EM Epitope Mapping",
    subtitle = "Structural Determination of INCA035784 and Antagonist mAb Binding Sites"
  ) %>%
  cols_label(
    Finding = "Finding",
    Detail = "Detail"
  ) %>%
  tab_style(
    style = cell_text(weight = "bold"),
    locations = cells_column_labels()
  ) %>%
  tab_style(
    style = cell_fill(color = "#f8f9fa"),
    locations = cells_body(rows = seq(2, nrow(structural_data), 2))
  ) %>%
  cols_width(
    Finding ~ px(220),
    Detail ~ px(480)
  ) %>%
  tab_footnote(
    footnote = "Cryo-EM = cryogenic electron microscopy; Fab = fragment of antigen binding; mAb = monoclonal antibody",
    locations = cells_column_labels(columns = Finding)
  ) %>%
  tab_footnote(
    footnote = "Non-overlapping epitopes between INCA035784 (N-domain) and the mutCALR antagonist mAb (C-domain region) suggest potential for combination therapy",
    locations = cells_body(columns = Finding, rows = 3)
  )

Finding¹	Detail
Cryo-EM Epitope Mapping
Structural Determination of INCA035784 and Antagonist mAb Binding Sites
INCA035784 Fab binding site	N-domain of mutCALR — conserved region unaffected by C-terminal mutations
mutCALR antagonist mAb binding site	Near C-domain region of mutCALR — distinct from INCA035784 epitope
Epitope relationship²	Non-overlapping epitopes — INCA035784 and antagonist mAb bind distinct regions, enabling potential combination
2D classification	14 nm complex visualized by 2D classification of cryo-EM images
CALR domain structure	N-domain (INCA035784 target) → P-domain → C-domain (mutated region; antagonist mAb target)
¹ Cryo-EM = cryogenic electron microscopy; Fab = fragment of antigen binding; mAb = monoclonal antibody
² Non-overlapping epitopes between INCA035784 (N-domain) and the mutCALR antagonist mAb (C-domain region) suggest potential for combination therapy

9 In Vitro Binding Specificity

Code

# Create binding specificity data
binding_data <- data.frame(
  Experiment = c(
    "TF-1 Type 1 mutCALR binding",
    "TF-1 Type 2 mutCALR binding",
    "TF-1 Parental (no mutCALR) binding",
    "Patient CD34+ Type 1 mutCALR expression",
    "Patient CD34+ Type 2 mutCALR expression",
    "Healthy donor CD34+ mutCALR expression",
    "Reh cells (wtCALR, doxorubicin-induced): INCA035784",
    "Reh cells (wtCALR, doxorubicin-induced): bivalent mutCALR×mutCALR",
    "Reh cells (wtCALR, doxorubicin-induced): wtCALR Ab (positive control)"
  ),
  Cell_System = c(
    "Isogenic TF-1 clones", "Isogenic TF-1 clones", "Isogenic TF-1 clones",
    "Patient-derived CD34+", "Patient-derived CD34+", "Healthy donor CD34+",
    "Reh ALL cell line", "Reh ALL cell line", "Reh ALL cell line"
  ),
  Result = c(
    "Positive — dose-dependent (gMFI ~3000 at saturation)",
    "Positive — equipotent with Type 1 (gMFI ~3000 at saturation)",
    "Negative — flat baseline (gMFI ~300)",
    "Positive — confirmed by flow cytometry",
    "Positive — confirmed by flow cytometry",
    "Negative — no mutCALR expression detected",
    "Negative — no binding at 50 μg/mL",
    "Negative — no binding (same mutCALR arms as INCA035784)",
    "Positive — confirms surface wtCALR is present"
  ),
  Interpretation = c(
    "Target engagement confirmed",
    "Equipotent across mutation types",
    "No off-target binding to cells without mutCALR",
    "Clinical translatability — Type 1",
    "Clinical translatability — Type 2",
    "No binding to normal hematopoietic cells",
    "Selectivity: does not recognize wtCALR on cell surface",
    "Confirms mutCALR arm specificity for mutant form only",
    "Validates assay — wtCALR is present but INCA035784 does not bind"
  )
)

9.1 Table 4: Comprehensive Binding Specificity Profile

Code

binding_data %>%
  gt() %>%
  tab_header(
    title = "INCA035784 Binding Specificity",
    subtitle = "Target Engagement Across Isogenic, Patient-Derived, and Wild-Type CALR Systems"
  ) %>%
  cols_label(
    Experiment = "Experiment",
    Cell_System = "Cell System",
    Result = "Result",
    Interpretation = "Interpretation"
  ) %>%
  tab_style(
    style = cell_text(weight = "bold"),
    locations = cells_column_labels()
  ) %>%
  tab_style(
    style = cell_fill(color = "#d4edda"),
    locations = cells_body(rows = c(1, 2, 4, 5))
  ) %>%
  tab_style(
    style = cell_fill(color = "#f8d7da"),
    locations = cells_body(rows = c(3, 6, 7, 8))
  ) %>%
  tab_style(
    style = cell_fill(color = "#fff3cd"),
    locations = cells_body(rows = 9)
  ) %>%
  tab_style(
    style = cell_text(size = px(11)),
    locations = cells_body()
  ) %>%
  cols_width(
    Experiment ~ px(200),
    Cell_System ~ px(120),
    Result ~ px(200),
    Interpretation ~ px(200)
  ) %>%
  tab_footnote(
    footnote = "gMFI = geometric mean fluorescence intensity; data from 2 independent experiments. Green = positive binding (desired); Red = no binding (desired for selectivity); Yellow = assay validation control.",
    locations = cells_column_labels(columns = Result)
  ) %>%
  tab_footnote(
    footnote = "Reh: ALL cell line with intracellular wtCALR. Doxorubicin used as stress agent to induce surface translocation. Surface exposure confirmed by wtCALR-specific antibody (Abcam, PE conjugated). Binding analysis performed using FlowJo v10.8.1 (BD Life Sciences).",
    locations = cells_body(columns = Experiment, rows = 7)
  )

Experiment	Cell System	Result¹	Interpretation
INCA035784 Binding Specificity
Target Engagement Across Isogenic, Patient-Derived, and Wild-Type CALR Systems
TF-1 Type 1 mutCALR binding	Isogenic TF-1 clones	Positive — dose-dependent (gMFI ~3000 at saturation)	Target engagement confirmed
TF-1 Type 2 mutCALR binding	Isogenic TF-1 clones	Positive — equipotent with Type 1 (gMFI ~3000 at saturation)	Equipotent across mutation types
TF-1 Parental (no mutCALR) binding	Isogenic TF-1 clones	Negative — flat baseline (gMFI ~300)	No off-target binding to cells without mutCALR
Patient CD34+ Type 1 mutCALR expression	Patient-derived CD34+	Positive — confirmed by flow cytometry	Clinical translatability — Type 1
Patient CD34+ Type 2 mutCALR expression	Patient-derived CD34+	Positive — confirmed by flow cytometry	Clinical translatability — Type 2
Healthy donor CD34+ mutCALR expression	Healthy donor CD34+	Negative — no mutCALR expression detected	No binding to normal hematopoietic cells
Reh cells (wtCALR, doxorubicin-induced): INCA035784²	Reh ALL cell line	Negative — no binding at 50 μg/mL	Selectivity: does not recognize wtCALR on cell surface
Reh cells (wtCALR, doxorubicin-induced): bivalent mutCALR×mutCALR	Reh ALL cell line	Negative — no binding (same mutCALR arms as INCA035784)	Confirms mutCALR arm specificity for mutant form only
Reh cells (wtCALR, doxorubicin-induced): wtCALR Ab (positive control)	Reh ALL cell line	Positive — confirms surface wtCALR is present	Validates assay — wtCALR is present but INCA035784 does not bind
¹ gMFI = geometric mean fluorescence intensity; data from 2 independent experiments. Green = positive binding (desired); Red = no binding (desired for selectivity); Yellow = assay validation control.
² Reh: ALL cell line with intracellular wtCALR. Doxorubicin used as stress agent to induce surface translocation. Surface exposure confirmed by wtCALR-specific antibody (Abcam, PE conjugated). Binding analysis performed using FlowJo v10.8.1 (BD Life Sciences).

10 In Vitro Functional Activity

Code

# Create TF-1 functional activity data with specific assay conditions
tf1_functional_data <- data.frame(
  Assay = c(
    "T Cell Activation (CD69+ on CD8+ T cells)",
    "T Cell-Mediated Cytotoxicity (CFSE+ L/D+ cells)",
    "T Cell Proliferation (CD8+ T cells)"
  ),
  ET_Ratio = c("5:1", "5:1", "5:1"),
  Incubation = c("72 hours", "72 hours", "120 hours"),
  Type_1_Result = c(
    "Dose-dependent; plateau ~80-90%",
    "Dose-dependent; plateau ~80%",
    "Dose-dependent; plateau ~70-80%"
  ),
  Type_2_Result = c(
    "Dose-dependent; equipotent with Type 1",
    "Dose-dependent; equipotent with Type 1",
    "Dose-dependent; equipotent with Type 1"
  ),
  Parental_Result = c(
    "Background levels only (~5%)",
    "Background levels only (<10%)",
    "Background levels only (~10%)"
  )
)

# Create MARIMO cell line data
marimo_data <- data.frame(
  Cell_Line = c(
    "TpoR MARIMO (type-1-like mutCALR)",
    "TpoR MARIMO (type-1-like mutCALR)",
    "HEL (JAK2V617F; control)",
    "HEL (JAK2V617F; control)"
  ),
  Antibody = c(
    "INCA035784 (mutCALR×CD3)",
    "Mock arm × CD3",
    "INCA035784 (mutCALR×CD3)",
    "Mock arm × CD3"
  ),
  ET_Ratio = rep("1:1", 4),
  Incubation = rep("72 hours", 4),
  Result = c(
    "Dose-dependent killing (10-75% at 0.005-1 μg/mL)",
    "No killing (cell proliferation observed)",
    "No killing (cell proliferation observed)",
    "No killing (cell proliferation observed)"
  )
)

# Create patient-derived CD34+ data
patient_cd34_data <- data.frame(
  Cell_Source = c(
    "Healthy donor CD34+ cells",
    "Type 1 mutCALR patient CD34+ cells",
    "Type 2 mutCALR patient CD34+ cells"
  ),
  mutCALR_Expression = c("Negative", "Positive (flow cytometry)", "Positive (flow cytometry)"),
  T_Cell_Activation_CD25 = c(
    "Minimal (~25-30% background)",
    "Dose-dependent (up to ~60-70%)",
    "Dose-dependent (up to ~60-70%)"
  ),
  Cytotoxicity = c(
    "Minimal (background levels)",
    "Dose-dependent (up to ~40%)",
    "Dose-dependent (up to ~45%)"
  ),
  Assay_Conditions = c(
    "5:1 E:T; 120h (cytotox), 72h (activ)",
    "5:1 E:T; 120h (cytotox), 72h (activ)",
    "5:1 E:T; 120h (cytotox), 72h (activ)"
  )
)

10.1 Table 5: T Cell-Mediated Functions in Isogenic TF-1 Cell Lines

Code

tf1_functional_data %>%
  gt() %>%
  tab_header(
    title = "INCA035784 Functional Activity in Isogenic TF-1 Clones",
    subtitle = "T Cell Activation, Cytotoxicity, and Proliferation"
  ) %>%
  cols_label(
    Assay = "Functional Assay",
    ET_Ratio = "E:T Ratio",
    Incubation = "Incubation",
    Type_1_Result = "TF-1 Type 1 mutCALR",
    Type_2_Result = "TF-1 Type 2 mutCALR",
    Parental_Result = "TF-1 Parental (No mutCALR)"
  ) %>%
  tab_style(
    style = cell_text(weight = "bold"),
    locations = cells_column_labels()
  ) %>%
  tab_style(
    style = cell_fill(color = "#d4edda"),
    locations = cells_body(columns = c(Type_1_Result, Type_2_Result))
  ) %>%
  tab_style(
    style = cell_fill(color = "#f8d7da"),
    locations = cells_body(columns = Parental_Result)
  ) %>%
  tab_style(
    style = cell_text(size = px(11)),
    locations = cells_body()
  ) %>%
  cols_width(
    Assay ~ px(180),
    ET_Ratio ~ px(60),
    Incubation ~ px(75),
    Type_1_Result ~ px(160),
    Type_2_Result ~ px(160),
    Parental_Result ~ px(140)
  ) %>%
  tab_footnote(
    footnote = "E:T = Effector to Target ratio; CFSE = carboxyfluorescein succinimidyl ester; L/D = live/dead. Data representative of assays with 2 different healthy T cell donors. Effector cells: healthy donor T cells.",
    locations = cells_column_labels(columns = Assay)
  )

Functional Assay¹	E:T Ratio	Incubation	TF-1 Type 1 mutCALR	TF-1 Type 2 mutCALR	TF-1 Parental (No mutCALR)
INCA035784 Functional Activity in Isogenic TF-1 Clones
T Cell Activation, Cytotoxicity, and Proliferation
T Cell Activation (CD69+ on CD8+ T cells)	5:1	72 hours	Dose-dependent; plateau ~80-90%	Dose-dependent; equipotent with Type 1	Background levels only (~5%)
T Cell-Mediated Cytotoxicity (CFSE+ L/D+ cells)	5:1	72 hours	Dose-dependent; plateau ~80%	Dose-dependent; equipotent with Type 1	Background levels only (<10%)
T Cell Proliferation (CD8+ T cells)	5:1	120 hours	Dose-dependent; plateau ~70-80%	Dose-dependent; equipotent with Type 1	Background levels only (~10%)
¹ E:T = Effector to Target ratio; CFSE = carboxyfluorescein succinimidyl ester; L/D = live/dead. Data representative of assays with 2 different healthy T cell donors. Effector cells: healthy donor T cells.

10.2 Table 6: Cytotoxicity in MARIMO Cell Line (Type-1-Like mutCALR)

Code

marimo_data %>%
  gt() %>%
  tab_header(
    title = "INCA035784 Killing Specificity: MARIMO vs HEL Cell Lines",
    subtitle = "Healthy Donor T Cell-Mediated Killing (1:1 E:T, 72 hours)"
  ) %>%
  cols_label(
    Cell_Line = "Target Cell Line",
    Antibody = "Antibody",
    ET_Ratio = "E:T",
    Incubation = "Time",
    Result = "Result"
  ) %>%
  tab_style(
    style = cell_text(weight = "bold"),
    locations = cells_column_labels()
  ) %>%
  tab_style(
    style = cell_fill(color = "#d4edda"),
    locations = cells_body(rows = 1)
  ) %>%
  tab_style(
    style = cell_fill(color = "#f8d7da"),
    locations = cells_body(rows = c(2, 3, 4))
  ) %>%
  tab_style(
    style = cell_text(size = px(11)),
    locations = cells_body()
  ) %>%
  cols_width(
    Cell_Line ~ px(180),
    Antibody ~ px(150),
    ET_Ratio ~ px(50),
    Incubation ~ px(60),
    Result ~ px(280)
  ) %>%
  tab_footnote(
    footnote = "TpoR MARIMO: type-1-like mutCALR-expressing cell line. HEL: JAK2V617F-mutant erythroleukemia cell line (negative control — no CALR mutation). Mock arm × CD3: control bispecific with non-targeting arm. Data from 3 independent experiments.",
    locations = cells_body(columns = Cell_Line, rows = 1)
  ) %>%
  tab_footnote(
    footnote = "INCA035784 selectively kills MARIMO (mutCALR+) but not HEL (JAK2V617F, CALR-WT), confirming mutation-specific targeting. Mock arm × CD3 shows no killing, confirming requirement for mutCALR arm engagement.",
    locations = cells_body(columns = Result, rows = 1)
  )

Target Cell Line	Antibody	E:T	Time	Result
INCA035784 Killing Specificity: MARIMO vs HEL Cell Lines
Healthy Donor T Cell-Mediated Killing (1:1 E:T, 72 hours)
TpoR MARIMO (type-1-like mutCALR)¹	INCA035784 (mutCALR×CD3)	1:1	72 hours	Dose-dependent killing (10-75% at 0.005-1 μg/mL)²
TpoR MARIMO (type-1-like mutCALR)	Mock arm × CD3	1:1	72 hours	No killing (cell proliferation observed)
HEL (JAK2V617F; control)	INCA035784 (mutCALR×CD3)	1:1	72 hours	No killing (cell proliferation observed)
HEL (JAK2V617F; control)	Mock arm × CD3	1:1	72 hours	No killing (cell proliferation observed)
¹ TpoR MARIMO: type-1-like mutCALR-expressing cell line. HEL: JAK2V617F-mutant erythroleukemia cell line (negative control — no CALR mutation). Mock arm × CD3: control bispecific with non-targeting arm. Data from 3 independent experiments.
² INCA035784 selectively kills MARIMO (mutCALR+) but not HEL (JAK2V617F, CALR-WT), confirming mutation-specific targeting. Mock arm × CD3 shows no killing, confirming requirement for mutCALR arm engagement.

10.3 Table 7: T Cell-Mediated Functions Against Patient-Derived CD34+ Cells

Code

patient_cd34_data %>%
  gt() %>%
  tab_header(
    title = "INCA035784 Activity Against Patient-Derived CD34+ Cells",
    subtitle = "Healthy Donor T Cell-Mediated Activation and Cytotoxicity"
  ) %>%
  cols_label(
    Cell_Source = "CD34+ Cell Source",
    mutCALR_Expression = "mutCALR Expression",
    T_Cell_Activation_CD25 = "T Cell Activation (% CD25+)",
    Cytotoxicity = "Cytotoxicity (%)",
    Assay_Conditions = "Assay Conditions"
  ) %>%
  tab_style(
    style = cell_text(weight = "bold"),
    locations = cells_column_labels()
  ) %>%
  tab_style(
    style = cell_fill(color = "#f8d7da"),
    locations = cells_body(rows = 1)
  ) %>%
  tab_style(
    style = cell_fill(color = "#d4edda"),
    locations = cells_body(rows = c(2, 3))
  ) %>%
  tab_style(
    style = cell_text(size = px(11)),
    locations = cells_body()
  ) %>%
  cols_width(
    Cell_Source ~ px(140),
    mutCALR_Expression ~ px(120),
    T_Cell_Activation_CD25 ~ px(150),
    Cytotoxicity ~ px(120),
    Assay_Conditions ~ px(150)
  ) %>%
  tab_footnote(
    footnote = "mutCALR expression confirmed by flow cytometry: CX33045 (mutCALR Ab) vs CX00375 (isotype control). Analysis: FlowJo v10.8.1 (BD Life Sciences). Controls: Mock arm × CD3 and untreated co-culture.",
    locations = cells_body(columns = Cell_Source, rows = 2)
  )

CD34+ Cell Source	mutCALR Expression	T Cell Activation (% CD25+)	Cytotoxicity (%)	Assay Conditions
INCA035784 Activity Against Patient-Derived CD34+ Cells
Healthy Donor T Cell-Mediated Activation and Cytotoxicity
Healthy donor CD34+ cells	Negative	Minimal (~25-30% background)	Minimal (background levels)	5:1 E:T; 120h (cytotox), 72h (activ)
Type 1 mutCALR patient CD34+ cells¹	Positive (flow cytometry)	Dose-dependent (up to ~60-70%)	Dose-dependent (up to ~40%)	5:1 E:T; 120h (cytotox), 72h (activ)
Type 2 mutCALR patient CD34+ cells	Positive (flow cytometry)	Dose-dependent (up to ~60-70%)	Dose-dependent (up to ~45%)	5:1 E:T; 120h (cytotox), 72h (activ)
¹ mutCALR expression confirmed by flow cytometry: CX33045 (mutCALR Ab) vs CX00375 (isotype control). Analysis: FlowJo v10.8.1 (BD Life Sciences). Controls: Mock arm × CD3 and untreated co-culture.

11 Cytokine Release Syndrome (CRS) Risk Assessment

Code

# Create detailed cytokine data
cytokine_detail <- data.frame(
  Cytokine = c(
    "IFN-γ", "IFN-γ",
    "IL-6", "IL-6",
    "TNF-α", "TNF-α"
  ),
  Antibody = c(
    "INCA035784 (mutCALR×CD3)", "Vibecotamab (CD123×CD3)",
    "INCA035784 (mutCALR×CD3)", "Vibecotamab (CD123×CD3)",
    "INCA035784 (mutCALR×CD3)", "Vibecotamab (CD123×CD3)"
  ),
  Cell_Source = rep("Healthy donor PBMCs", 6),
  Max_Induction = c(
    "Minimal (at/near anti-RSV control levels)",
    "~10,000-15,000 pg/mL (dose-dependent)",
    "Minimal (at/near anti-RSV control levels)",
    "~300-350 pg/mL (dose-dependent)",
    "Minimal (at/near anti-RSV control levels)",
    "~300-400 pg/mL (dose-dependent)"
  ),
  Assessment = c(
    "Favorable", "CRS risk signal",
    "Favorable", "CRS risk signal",
    "Favorable", "CRS risk signal"
  )
)

11.1 Table 8: CRS-Associated Cytokine Induction

Code

cytokine_detail %>%
  gt() %>%
  tab_header(
    title = "Cytokine Release Syndrome Risk Assessment",
    subtitle = "INCA035784 vs Vibecotamab in Healthy Donor PBMCs"
  ) %>%
  cols_label(
    Cytokine = "Cytokine",
    Antibody = "Antibody",
    Cell_Source = "Cell Source",
    Max_Induction = "Maximum Induction",
    Assessment = "Assessment"
  ) %>%
  tab_style(
    style = cell_text(weight = "bold"),
    locations = cells_column_labels()
  ) %>%
  tab_style(
    style = cell_fill(color = "#d4edda"),
    locations = cells_body(rows = c(1, 3, 5))
  ) %>%
  tab_style(
    style = cell_fill(color = "#fff3cd"),
    locations = cells_body(rows = c(2, 4, 6))
  ) %>%
  tab_style(
    style = cell_text(size = px(11)),
    locations = cells_body()
  ) %>%
  cols_width(
    Cytokine ~ px(80),
    Antibody ~ px(160),
    Cell_Source ~ px(100),
    Max_Induction ~ px(220),
    Assessment ~ px(80)
  ) %>%
  tab_footnote(
    footnote = "Graphs representative of 3 independent experiments. Anti-RSV antibody = negative control. IFN-γ = interferon gamma; IL-6 = interleukin 6; TNF-α = tumor necrosis factor alpha. Vibecotamab (CD123×CD3): comparator T cell-engaging antibody in development for AML.",
    locations = cells_column_labels(columns = Max_Induction)
  )

Cytokine	Antibody	Cell Source	Maximum Induction¹	Assessment
Cytokine Release Syndrome Risk Assessment
INCA035784 vs Vibecotamab in Healthy Donor PBMCs
IFN-γ	INCA035784 (mutCALR×CD3)	Healthy donor PBMCs	Minimal (at/near anti-RSV control levels)	Favorable
IFN-γ	Vibecotamab (CD123×CD3)	Healthy donor PBMCs	~10,000-15,000 pg/mL (dose-dependent)	CRS risk signal
IL-6	INCA035784 (mutCALR×CD3)	Healthy donor PBMCs	Minimal (at/near anti-RSV control levels)	Favorable
IL-6	Vibecotamab (CD123×CD3)	Healthy donor PBMCs	~300-350 pg/mL (dose-dependent)	CRS risk signal
TNF-α	INCA035784 (mutCALR×CD3)	Healthy donor PBMCs	Minimal (at/near anti-RSV control levels)	Favorable
TNF-α	Vibecotamab (CD123×CD3)	Healthy donor PBMCs	~300-400 pg/mL (dose-dependent)	CRS risk signal
¹ Graphs representative of 3 independent experiments. Anti-RSV antibody = negative control. IFN-γ = interferon gamma; IL-6 = interleukin 6; TNF-α = tumor necrosis factor alpha. Vibecotamab (CD123×CD3): comparator T cell-engaging antibody in development for AML.

12 In Vivo Efficacy: Autologous MF Patient-Derived Xenograft (PDX) Model

Code

# Create PDX model design data
pdx_design <- data.frame(
  Parameter = c(
    "Mouse model",
    "Patient source",
    "CALR mutation type",
    "Patient mutCALR VAF",
    "Tumor cell inoculation",
    "Cell number (tumor)",
    "Engraftment period",
    "T cell source",
    "T cell number",
    "T cell administration",
    "Antibody administration",
    "Antibody doses tested",
    "Treatment duration",
    "Endpoint analyses"
  ),
  Detail = c(
    "NSGS mice (NOD/SCID IL2RG knockout with cytokine expression)",
    "Type 2 mutCALR myelofibrosis patient",
    "Type 2 mutCALR",
    "89.6%",
    "Intratibial injection of patient-derived CD34+ cells",
    "1×10⁵ cells/mouse",
    "4 weeks (until peripheral blood hCD45+ engraftment confirmed)",
    "Autologous/patient-matched T cells",
    "1×10⁶ cells/mouse",
    "Intravenous (at randomization)",
    "Intraperitoneal, weekly for 4 weeks",
    "0.03 mg/kg and 0.2 mg/kg",
    "4 weeks (Week 1 through Week 4 post-randomization)",
    "Bone marrow flow cytometry (megakaryocyte, myeloid, erythroid progenitors)"
  )
)

# Create PDX efficacy results
pdx_results <- data.frame(
  Compartment = c(
    "Megakaryocyte progenitors (hCD45+hCD41+)",
    "Megakaryocyte progenitors (hCD45+hCD41+)",
    "Myeloid cells (hCD45+hCD33+)",
    "Myeloid cells (hCD45+hCD33+)",
    "Erythroid cell progenitors (hCD45+hCD71+)",
    "Erythroid cell progenitors (hCD45+hCD71+)"
  ),
  Dose = c(
    "0.03 mg/kg", "0.2 mg/kg",
    "0.03 mg/kg", "0.2 mg/kg",
    "0.03 mg/kg", "0.2 mg/kg"
  ),
  Effect_vs_Untreated = c(
    "Significant reduction", "Significant reduction",
    "Significant reduction", "Significant reduction",
    "No significant effect", "No significant effect"
  ),
  P_Value = c(
    "<0.01", "<0.01",
    "<0.01", "<0.01",
    "ns", "ns"
  ),
  Interpretation = c(
    "Target cell depletion in BM", "Target cell depletion in BM",
    "Myeloid compartment reduction", "Myeloid compartment reduction",
    "Erythroid lineage spared", "Erythroid lineage spared"
  )
)

12.1 Table 9: PDX Model Design

Code

pdx_design %>%
  gt() %>%
  tab_header(
    title = "Autologous MF Patient-Derived Xenograft Model Design",
    subtitle = "In Vivo Efficacy Assessment of INCA035784"
  ) %>%
  cols_label(
    Parameter = "Parameter",
    Detail = "Detail"
  ) %>%
  tab_style(
    style = cell_text(weight = "bold"),
    locations = cells_column_labels()
  ) %>%
  tab_style(
    style = cell_fill(color = "#f8f9fa"),
    locations = cells_body(rows = seq(2, nrow(pdx_design), 2))
  ) %>%
  tab_footnote(
    footnote = "NSGS = NOD/SCID IL2RG knockout with human cytokine expression; VAF = Variant Allele Frequency; hCD45+ = human CD45-positive",
    locations = cells_body(columns = Parameter, rows = 1)
  ) %>%
  tab_footnote(
    footnote = "Autologous/patient-matched T cells ensure physiological relevance of T cell-mediated killing",
    locations = cells_body(columns = Parameter, rows = 8)
  )

Parameter	Detail
Autologous MF Patient-Derived Xenograft Model Design
In Vivo Efficacy Assessment of INCA035784
Mouse model¹	NSGS mice (NOD/SCID IL2RG knockout with cytokine expression)
Patient source	Type 2 mutCALR myelofibrosis patient
CALR mutation type	Type 2 mutCALR
Patient mutCALR VAF	89.6%
Tumor cell inoculation	Intratibial injection of patient-derived CD34+ cells
Cell number (tumor)	1×10⁵ cells/mouse
Engraftment period	4 weeks (until peripheral blood hCD45+ engraftment confirmed)
T cell source²	Autologous/patient-matched T cells
T cell number	1×10⁶ cells/mouse
T cell administration	Intravenous (at randomization)
Antibody administration	Intraperitoneal, weekly for 4 weeks
Antibody doses tested	0.03 mg/kg and 0.2 mg/kg
Treatment duration	4 weeks (Week 1 through Week 4 post-randomization)
Endpoint analyses	Bone marrow flow cytometry (megakaryocyte, myeloid, erythroid progenitors)
¹ NSGS = NOD/SCID IL2RG knockout with human cytokine expression; VAF = Variant Allele Frequency; hCD45+ = human CD45-positive
² Autologous/patient-matched T cells ensure physiological relevance of T cell-mediated killing

12.2 Table 10: PDX Model Efficacy Results

Code

pdx_results %>%
  gt() %>%
  tab_header(
    title = "In Vivo Efficacy: Bone Marrow Cell Populations",
    subtitle = "INCA035784 Treatment in Autologous MF PDX Model"
  ) %>%
  cols_label(
    Compartment = "Cell Population (Markers)",
    Dose = "INCA035784 Dose",
    Effect_vs_Untreated = "Effect vs Untreated + T cells",
    P_Value = "P Value",
    Interpretation = "Interpretation"
  ) %>%
  tab_style(
    style = cell_text(weight = "bold"),
    locations = cells_column_labels()
  ) %>%
  tab_style(
    style = cell_fill(color = "#d4edda"),
    locations = cells_body(rows = c(1, 2, 3, 4))
  ) %>%
  tab_style(
    style = cell_fill(color = "#cfe2ff"),
    locations = cells_body(rows = c(5, 6))
  ) %>%
  cols_width(
    Compartment ~ px(200),
    Dose ~ px(90),
    Effect_vs_Untreated ~ px(130),
    P_Value ~ px(70),
    Interpretation ~ px(160)
  ) %>%
  tab_footnote(
    footnote = "**P<0.01 vs untreated group (1-way ANOVA); ns = not significant. BM = bone marrow.",
    locations = cells_column_labels(columns = P_Value)
  ) %>%
  tab_footnote(
    footnote = "Selective depletion of megakaryocyte progenitors and myeloid cells with preservation of erythroid progenitors supports lineage-selective activity of INCA035784 in vivo",
    locations = cells_body(columns = Interpretation, rows = 5)
  )

Cell Population (Markers)	INCA035784 Dose	Effect vs Untreated + T cells	P Value¹	Interpretation
In Vivo Efficacy: Bone Marrow Cell Populations
INCA035784 Treatment in Autologous MF PDX Model
Megakaryocyte progenitors (hCD45+hCD41+)	0.03 mg/kg	Significant reduction	<0.01	Target cell depletion in BM
Megakaryocyte progenitors (hCD45+hCD41+)	0.2 mg/kg	Significant reduction	<0.01	Target cell depletion in BM
Myeloid cells (hCD45+hCD33+)	0.03 mg/kg	Significant reduction	<0.01	Myeloid compartment reduction
Myeloid cells (hCD45+hCD33+)	0.2 mg/kg	Significant reduction	<0.01	Myeloid compartment reduction
Erythroid cell progenitors (hCD45+hCD71+)	0.03 mg/kg	No significant effect	ns	Erythroid lineage spared²
Erythroid cell progenitors (hCD45+hCD71+)	0.2 mg/kg	No significant effect	ns	Erythroid lineage spared
¹ **P<0.01 vs untreated group (1-way ANOVA); ns = not significant. BM = bone marrow.
² Selective depletion of megakaryocyte progenitors and myeloid cells with preservation of erythroid progenitors supports lineage-selective activity of INCA035784 in vivo

13 Relationship to INCA33989 (Anti-mutCALR Monoclonal Antibody)

Code

# Compare INCA035784 (TCE) vs INCA33989 (mAb)
pipeline_comparison <- data.frame(
  Feature = c(
    "Molecule type",
    "Target",
    "Mechanism of action",
    "Fc modification",
    "Epitope on mutCALR",
    "Development stage",
    "Clinical trial",
    "Patient population",
    "Mutation coverage",
    "Key differentiation",
    "In vivo evidence"
  ),
  INCA035784_TCE = c(
    "Bispecific T cell-redirecting antibody",
    "mutCALR (N-domain) × CD3",
    "T cell-mediated cytotoxicity of mutCALR+ cells",
    "Fc-silenced",
    "N-domain (conserved; distinct from antagonist mAb)",
    "Preclinical → entering Phase 1",
    "NCT07008118",
    "MPN patients with CALR mutations",
    "Equipotent across Type 1, Type 2, and other CALR mutations",
    "Curative potential via T cell-mediated clone elimination; targets disease-initiating CD34+ cells",
    "Autologous MF PDX: significant reduction of MK progenitors and myeloid cells (P<0.01); erythroid spared"
  ),
  INCA33989_mAb = c(
    "Monoclonal antibody (non-T cell engaging)",
    "mutCALR (C-domain region)",
    "Selective depletion of mutCALR+ cells (Fc-effector independent)",
    "Fc-silenced",
    "C-domain region (distinct from INCA035784)",
    "Phase 1 (ASH 2025; N=51 ET patients)",
    "NCT05936359 / NCT06034002",
    "mutCALR ET and MF",
    "Type 1 (55%), Type 2 (29%), Other (16%)",
    "Disease modification via selective clone reduction; 80% CHR+PHR, 90% VAF reduction",
    "Clinical Phase 1: 73% CHR, 44% molecular response (≥20% VAF↓), 94% treatment continuation"
  )
)

13.1 Table 11: Incyte mutCALR-Targeting Pipeline Comparison

Code

pipeline_comparison %>%
  gt() %>%
  tab_header(
    title = "Incyte mutCALR-Targeting Pipeline",
    subtitle = "INCA035784 (T Cell Engager) vs INCA33989 (Monoclonal Antibody)"
  ) %>%
  cols_label(
    Feature = "Feature",
    INCA035784_TCE = "INCA035784 (TCE)",
    INCA33989_mAb = "INCA33989 (mAb)"
  ) %>%
  tab_style(
    style = cell_text(weight = "bold"),
    locations = cells_column_labels()
  ) %>%
  tab_style(
    style = cell_fill(color = "#e8f5e8"),
    locations = cells_body(columns = INCA035784_TCE)
  ) %>%
  tab_style(
    style = cell_fill(color = "#cfe2ff"),
    locations = cells_body(columns = INCA33989_mAb)
  ) %>%
  tab_style(
    style = cell_text(size = px(11)),
    locations = cells_body(columns = c(INCA035784_TCE, INCA33989_mAb))
  ) %>%
  cols_width(
    Feature ~ px(130),
    INCA035784_TCE ~ px(280),
    INCA33989_mAb ~ px(280)
  ) %>%
  tab_footnote(
    footnote = "TCE = T Cell Engager; mAb = Monoclonal Antibody; MPN = Myeloproliferative Neoplasm; ET = Essential Thrombocythemia; MF = Myelofibrosis; CHR = Complete Hematologic Response; PHR = Partial Hematologic Response; VAF = Variant Allele Frequency; MK = Megakaryocyte",
    locations = cells_column_labels(columns = Feature)
  ) %>%
  tab_footnote(
    footnote = "Both molecules are Fc-silenced but bind distinct, non-overlapping epitopes (N-domain vs C-domain region), supporting potential for combination therapy",
    locations = cells_body(columns = Feature, rows = 5)
  )

Feature¹	INCA035784 (TCE)	INCA33989 (mAb)
Incyte mutCALR-Targeting Pipeline
INCA035784 (T Cell Engager) vs INCA33989 (Monoclonal Antibody)
Molecule type	Bispecific T cell-redirecting antibody	Monoclonal antibody (non-T cell engaging)
Target	mutCALR (N-domain) × CD3	mutCALR (C-domain region)
Mechanism of action	T cell-mediated cytotoxicity of mutCALR+ cells	Selective depletion of mutCALR+ cells (Fc-effector independent)
Fc modification	Fc-silenced	Fc-silenced
Epitope on mutCALR²	N-domain (conserved; distinct from antagonist mAb)	C-domain region (distinct from INCA035784)
Development stage	Preclinical → entering Phase 1	Phase 1 (ASH 2025; N=51 ET patients)
Clinical trial	NCT07008118	NCT05936359 / NCT06034002
Patient population	MPN patients with CALR mutations	mutCALR ET and MF
Mutation coverage	Equipotent across Type 1, Type 2, and other CALR mutations	Type 1 (55%), Type 2 (29%), Other (16%)
Key differentiation	Curative potential via T cell-mediated clone elimination; targets disease-initiating CD34+ cells	Disease modification via selective clone reduction; 80% CHR+PHR, 90% VAF reduction
In vivo evidence	Autologous MF PDX: significant reduction of MK progenitors and myeloid cells (P<0.01); erythroid spared	Clinical Phase 1: 73% CHR, 44% molecular response (≥20% VAF↓), 94% treatment continuation
¹ TCE = T Cell Engager; mAb = Monoclonal Antibody; MPN = Myeloproliferative Neoplasm; ET = Essential Thrombocythemia; MF = Myelofibrosis; CHR = Complete Hematologic Response; PHR = Partial Hematologic Response; VAF = Variant Allele Frequency; MK = Megakaryocyte
² Both molecules are Fc-silenced but bind distinct, non-overlapping epitopes (N-domain vs C-domain region), supporting potential for combination therapy

14 Summary of Key Findings

14.1 Binding and Selectivity

Conserved N-domain epitope: Cryo-EM confirms INCA035784 binds the N-domain of mutCALR, which is structurally unaltered by C-terminal mutations (Type 1 deletions, Type 2 insertions, and other variants)
Equipotent activity: Demonstrated in isogenic TF-1 clones (gMFI ~3000 for both Type 1 and Type 2) and patient-derived CD34+ cells
No binding to wild-type CALR: Even when doxorubicin forces wtCALR to the cell surface in Reh cells, neither INCA035784 nor a bivalent mutCALR×mutCALR antibody binds — while a wtCALR-specific antibody confirms surface expression
Distinct epitope from antagonist mAb: INCA035784 (N-domain) and the mutCALR antagonist mAb (C-domain region) bind non-overlapping epitopes, enabling potential combination approaches

14.2 Functional Activity

Dose-dependent T cell activation, proliferation, and cytotoxicity in isogenic TF-1 cells expressing Type 1 and Type 2 mutCALR (5:1 E:T, 72-120 hours)
Selective killing of MARIMO cells (type-1-like mutCALR) but not HEL cells (JAK2V617F, CALR-WT) at 1:1 E:T ratio — confirming mutation-specific targeting with a non-isogenic cell system
Patient-derived CD34+ cell killing: Dose-dependent T cell activation (CD25) and cytotoxicity against CD34+ cells from Type 1 and Type 2 mutCALR patients, with no effect on healthy donor CD34+ cells
Disease-initiating cell targeting: Activity against CD34+ progenitor cells demonstrates potential to eliminate disease-initiating populations

14.3 In Vivo Efficacy

Autologous MF PDX model: Using Type 2 mutCALR patient-derived CD34+ cells (VAF 89.6%) with patient-matched T cells in NSGS mice
Significant reduction of megakaryocyte progenitors (hCD45+hCD41+) and myeloid cells (hCD45+hCD33+) at both 0.03 and 0.2 mg/kg (P<0.01 vs untreated)
Erythroid progenitors spared: No significant effect on hCD45+hCD71+ cells, supporting lineage-selective activity

14.4 Safety Signals

Minimal CRS-associated cytokine induction: IFN-γ, IL-6, and TNF-α levels remained at or near control antibody levels in healthy donor PBMCs, in contrast to vibecotamab (CD123×CD3) which showed robust dose-dependent induction

14.5 Clinical Implications

INCA035784 represents a first-in-class T cell-redirecting approach for MPN patients with CALR mutations
Curative potential through T cell-mediated elimination of the malignant clone, including disease-initiating CD34+ progenitors
Complementary to INCA33989 (antagonist mAb): distinct non-overlapping epitopes support potential combination strategies
Clinical trial NCT07008118 initiated for Phase 1 evaluation in mutCALR MPN patients
Together, INCA33989 (disease modification) and INCA035784 (curative intent) may offer a spectrum of treatment intensity for mutCALR MPN patients

Code

# Session information
sessionInfo()

R version 4.6.1 (2026-06-24)
Platform: aarch64-apple-darwin23
Running under: macOS Tahoe 26.6

Matrix products: default
BLAS:   /Library/Frameworks/R.framework/Versions/4.6/Resources/lib/libRblas.0.dylib 
LAPACK: /Library/Frameworks/R.framework/Versions/4.6/Resources/lib/libRlapack.dylib;  LAPACK version 3.12.1

locale:
[1] en_US.UTF-8/en_US.UTF-8/en_US.UTF-8/C/en_US.UTF-8/en_US.UTF-8

time zone: America/Chicago
tzcode source: internal

attached base packages:
[1] stats     graphics  grDevices utils     datasets  methods   base     

other attached packages:
[1] flextable_0.10.0 gtsummary_2.5.1  gt_1.3.0         ggplot2_4.0.3   
[5] dplyr_1.2.1      kableExtra_1.4.1 knitr_1.51      

loaded via a namespace (and not attached):
 [1] sass_0.4.10             tidyr_1.3.2             generics_0.1.4         
 [4] fontLiberation_0.1.0    xml2_1.6.0              stringi_1.8.7          
 [7] digest_0.6.39           magrittr_2.0.5          evaluate_1.0.5         
[10] grid_4.6.1              RColorBrewer_1.1-3      fastmap_1.2.0          
[13] jsonlite_2.0.0          zip_3.0.2               purrr_1.2.2            
[16] viridisLite_0.4.3       scales_1.4.0            fontBitstreamVera_0.1.1
[19] textshaping_1.0.5       cli_3.6.6               rlang_1.3.0            
[22] fontquiver_0.2.1        withr_3.0.3             yaml_2.3.12            
[25] otel_0.2.0              gdtools_0.5.1           tools_4.6.1            
[28] officer_0.7.6           uuid_1.2-2              vctrs_0.7.3            
[31] R6_2.6.1                lifecycle_1.0.5         stringr_1.6.0          
[34] fs_2.1.0                htmlwidgets_1.6.4       ragg_1.5.2             
[37] pkgconfig_2.0.3         pillar_1.11.1           gtable_0.3.6           
[40] glue_1.8.1              data.table_1.18.4       Rcpp_1.1.2             
[43] systemfonts_1.3.2       xfun_0.60               tibble_3.3.1           
[46] tidyselect_1.2.1        rstudioapi_0.19.0       farver_2.1.2           
[49] patchwork_1.3.2         htmltools_0.5.9         rmarkdown_2.31         
[52] svglite_2.2.2           compiler_4.6.1          S7_0.2.2               
[55] askpass_1.2.1           openssl_2.4.2