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Loncastuximab Tesirine (ADCT-402, Lonca) Targeting CD19

Lonca is an ADC composed of a humanized monoclonal antibody that binds to human CD19 and conjugated through a linker to a PBD-dimer toxin. Once bound to a CD19-expressing cell, Lonca is internalized into the cell where enzymes release the PBD-based warhead.

CD19 is an ideal target for an ADC approach

CD19 is highly expressed in a range of B-cell hematological tumors, including certain types of lymphoma and leukemia, while its expression in healthy tissue is restricted.

Lonca is the focus of the LOTIS Clinical Development Program

In clinical trials, lead candidate Lonca has demonstrated significant single-agent clinical activity across a broad population of patients with relapsed or refractory diffuse large B-cell, mantle cell, and follicular lymphomas.

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ADCT-602 Targeting CD22

ADCT-602 is an ADC composed of a monoclonal antibody that binds to CD22 conjugated to a PBD dimer toxin. Once bound to a CD22-expressing cell, ADCT-602 is internalized into the cell where enzymes release the PBD-based warhead. CD22 is an attractive and clinically validated ADC target. CD22 is highly expressed on most malignant B-cells, including expression in more than 90% of patients with B-cell acute lymphoblastic leukemia (ALL).

ADCT-602 is being evaluated in a phase I/II clinical trial in patients with relapsed or refractory B-cell ALL (NCT03698552). The trial is being led by The University of Texas MD Anderson Cancer Center.

ALLO-715: UNIVERSAL Study Targeting B Cell Maturation Antigen (BCMA) in Relapsed/Refractory Multiple Myeloma

Primary objective

• Safety and tolerability

Key secondary objectives

• Recommended ALLO-715 Phase 2 dose and lymphodepletion regimen​
• Anti-tumor activity (ORR, duration of response, PFS, and MRD)​
• ALLO-715 cellular kinetics (blood levels of anti-BCMA CAR T cells)​
• ALLO-647 pharmacokinetics (serum ALLO-647 concentrations)

Key eligibility criteria

• Relapsed/Refractory Multiple Myeloma
• ≥ 3 prior therapies, including an IMiD, a proteasome inhibitor, and an anti-CD38 antibody
• Refractory to last prior therapy
• ECOG 0 or 1
• No donor-specific antibodies
• No bridging therapy allowed

Treatment

• Dose escalation: 40, 160, and 320 x 106 CAR+ cells

Lymphodepletion

• ALLO-647: 13 to 30 mg x 3 days​
• Fludarabine: 30 mg/m2/d x 3 days​
• Cyclophosphamide: 300 mg/m2/d x 3 days

ALLO-715: Exploring Gamma Secretase Inhibition (GSI) in Multiple Myeloma

Potential increase in antitumor efficacy

• Nirogacestat increases B cell maturation antigen (BCMA) expression in MM cell lines¹​
• Others have shown that GSI may increase the antitumor efficacy of autologous BCMA-directed CAR T therapy²

¹Data on File. Allogene Therapeutics.​
²Blood. 2019;134(19):1585-1597. doi:10.1182/blood.2019000050

ALLO-605 TurboCAR™: Turbocharging CAR T Cells

Cytokine stimulation can increase the potency and durability of engineered T cells

TurboCAR™ is designed to recapitulate cytokine signaling selectively in CAR T cells and may have potential benefits, subject to investigation

• Minimizes systemic toxicity
• Does not stimulate host immune cells which could reject CAR
• Delivers survival benefit selectively to CAR T cells

Opportunities for development

• Improving the efficacy of CAR T cells
• Reducing CAR T cell dose requirement
• Overcoming exhaustion to enable CAR T therapies to be used for solid tumors

ALLO-316 (Anti-CD70): The Next AlloCAR T™ Clinical Candidate

ALLO-316 is an anti-CD70 AlloCAR T™ candidate for renal cell carcinoma (RCC) as well as several hematological malignancies

CD70 expression¹

• RCC (80%-100%)​
• Acute myeloid leukemia (96%)​
• Diffuse large B cell lymphoma (71%), multiple myeloma (63%), chronic lymphocytic leukemia (50%)​
• Glioblastoma mutiforme (35%)​
• CD70 is also expressed on activated T cells

CD70 in RCC

• High prevalence with limited off-tumor expression​
• Good expression in metastatic disease

ALLO-316 is associated with minimal or no fratricide

ALLO-819 targeting FLT3 is currently under development

ADCT-601 Targeting AXL

ADCT-601 is an ADC composed of a humanized monoclonal antibody that binds to human AXL (licensed from BerGenBio), conjugated using Glycoconnect™ technology (licensed from Synaffix BV) to a linker with a PBD-dimer toxin. Once bound to an AXL-expressing cell, ADCT-601 is internalized into the cell, where enzymes release the PBD-based warhead. AXL is an ideal target for an ADC approach, as it is highly overexpressed in many solid tumors (eg, lung, breast, prostate, pancreas, glioma, and esophageal) and hematological malignancies (eg, acute and chronic myeloid leukemia).

ADCT-601 is being evaluated in a phase 1 clinical trial in patients with selected advanced solid tumors (NCT03700294).

ADCT-901 Targeting KAAG1

ADCT-901 is an ADC composed of a humanized monoclonal antibody (3A4) directed against human KAAG1 and conjugated through a cathepsin-cleavable linker to SG3199, a PBD-dimer cytotoxin. KAAG1 is an attractive novel tumor target for ADC development as (i) it is an intracellular target by definition, but becomes exposed on the membrane of tumor cells, (ii) it has high expression in tumors with high unmet medical need, including ovarian cancer and triple negative breast cancer, while its expression on healthy tissue is very restricted, and (iii) it internalizes and co-localizes with lysosomal-associated membrane protein 1, a lysosomal marker, which shows that the target is efficiently transported to the cellular compartment where efficient release of the cytotoxin is expected.

ADCT-901 is being developed for the treatment of advanced solid tumors with high unmet medical needs, including platinum resistant ovarian cancer and triple negative breast cancer.

ALLO-316 (Anti-CD70): The Next AlloCAR T™ Clinical Candidate

ALLO-316 is an anti-CD70 AlloCAR T™ candidate for renal cell carcinoma (RCC) as well as several hematological malignancies

CD70 expression¹

• RCC (80%-100%)​
• Acute myeloid leukemia (96%)​
• Diffuse large B cell lymphoma (71%), multiple myeloma (63%), chronic lymphocytic leukemia (50%)​
• Glioblastoma mutiforme (35%)​
• CD70 is also expressed on activated T cells

CD70 in RCC

• High prevalence with limited off-tumor expression​
• Good expression in metastatic disease

ALLO-316 is associated with minimal or no fratricide

DLL3 is currently under development

ALLO-647 (Anti-CD52 mAb): Selective Lymphodepletion May Delay Graft Rejection

ALLO-647 intended to enable expansion and persistence of allogeneic CAR T product candidates. Host T cell recovery is delayed by addition of anti-CD52.