Pipeline

Overview

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ABL001

  • Pipeline
    ABL001
  • Program Target
    VEGF x DLL4
  • Disease Indication
    Solid Tumor
  • Development Stage
    Clinical Development
    (Phase 1a/1b)
Summary
Better anti-cancer efficacy of ABL001 at in vitro/in vivo studies are confirmed with cancer patients in clinical trial (phase 1a/1b).
ABL001 can be developed as the next generation of anti-angiogenic therapy.

MOA of ABL001

Dual blockade of VEGF & DLL4 overcomes VEGF resistance

MOA of ABL001
MOA of ABL001

POC of ABL001 in Preclinical Study

Better efficacy compared to Avastin or anti-DLL4 monotherapy

POC of ABL001 in Preclinical Study
POC of ABL001 in Preclinical Study

Clinical Response of ABL001

3 Patients showed confirmed partial response (PR) in phase 1a/1b study

Clinical Response of ABL001
좌우스크롤 Clinical Response of ABL001

Publications

좌우스크롤
Publications(Pipeline, Journal, Date, Title, Link, PDF)
Pipeline Journal Date Title Link PDF
ABL001 mAbs 2016 Simultaneous blockade of VEGF and Dll4 by HD105, a bispecific antibody, inhibits tumor progression and angiogenesis 링크정보 아이콘 PDF 아이콘
BMB Reports 2020 Synergistic antitumor activity of a DLL4/VEGF bispecific therapeutic antibody in combination with irinotecan in gastric cancer 링크정보 아이콘 PDF 아이콘
Int J Mol Sci 2020 ABL001, a bispecific antibody targeting VEGF and DLL4, with chemotherapy, synergistically inhibits tumor progression in xenograft models 링크정보 아이콘 PDF 아이콘

Posters

좌우스크롤
Posters(Pipeline, Name, Title, PDF)
Pipeline Name Title PDF
ABL001 PEGS 2017 Preclinical development of an anti-cancer bispecific antibody targeting VEGF and DLL4, ABL001 PDF 아이콘
ASCO 2019 Phase 1a study results investigating the safety and preliminary efficacy of ABL001 (NOV1501), a bispecific antibody targeting VEGF and DLL4 in metastatic gastrointesinal (GI) cancer PDF 아이콘
PEPTALK 2020 Summary of phase 1a dose escalation clinical study data for dual angiogenic bispecific antibody targeting VEGF and DLL4 (ABL001/NOV1501/TR009) in patients with previously treated solid tumors PDF 아이콘

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ABL105

  • Pipeline
    ABL105
  • Program Target
    HER2x4-1BB
  • Disease Indication
    Solid Tumor
  • Development Stage
    IND Submission
Summary
ABL105 is a bispecific antibody that simultaneously targets HER2 and 4-1BB, crosslinking and activating 4-1BB signaling only when in the presence of tumor cells. Done so in an HER2 expression-dependent manner, ABL105 does not induce T-cell activation in normal tissues lacking 4-1BB clustering. In addition, ABL105 blocks HER2 signaling and induces NK cell-mediated cytotoxicity, leading to stronger anti-tumor activity. ABL105 significantly inhibits tumor growth and protects mice from tumor recurrence by inducing tumor specific memory.

MOA of ABL105

ABL105 in the Grabody™-T BsAb Platform activates T-cells only in the Tumor Microenvironment

MOA of ABL105
MOA of ABL105

Tumor Specific 4-1BB Activation

ABL105 activates 4-1BB signaling only in the presence of tumor cells in a HER2 expression-dependent manner

Tumor Specific 4-1BB Activation
Tumor Specific 4-1BB Activation

Strong Anti-Tumor Effect

ABL105 inhibits tumor growth and protects mice from tumor re-challenge by inducing tumor specific memory

Strong Anti-Tumor Effect
좌우스크롤 Strong Anti-Tumor Effect

Posters

좌우스크롤
Posters(Pipeline, Name, Title, PDF)
Pipeline Name Title PDF
ABL105 ESMO A novel HER2/4-1BB bispecific antibody, YH32367 (ABL105) exerts significant anti-tumor effects through tumor-directed T cell activation PDF 아이콘

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ABL111

  • Pipeline
    ABL111
  • Program Target
    Claudin18.2x4-1BB
  • Disease Indication
    Solid Tumor
  • Development Stage
    Clinical Development
    (Phase 1)
Summary
ABL111 is a bispecific antibody that targets Claudin18.2, a tumor antigen overexpressed in gastric- and pancreatic-specific cancer, and 4-1BB, a co-stimulatory receptor with the ability to induce potent anti-tumor activity. To minimize the usual toxicity associated with monospecific 4-1BB based treatments, ABL111 only activates the 4-1BB pathway when engaged with Claudin 18.2, thus triggering T cell activation and enhancing anti-tumor immunity while minimizing toxicity. ABL111 shows superior anti-tumor activity in an animal model system compared to Claudin18.2 alone, 4-1BB alone, and the combination of both Claudin18.2 and 4-1BB, with immunological memory resistant to any possible recurrence of the cancer cells.

Structure and Mechanism of Action

Structure and Mechanism of Action
좌우스크롤 Structure and Mechanism of Action

Claudin18.2 Dependent 4-1BB Activation

Claudin18.2 Dependent 4-1BB Activation
Claudin18.2 Dependent 4-1BB Activation

Superior Anti-Tumor Effect with Immunological Memory

Superior Anti-Tumor Effect with Immunological Memory
좌우스크롤 Superior Anti-Tumor Effect with Immunological Memory

Increase of effector memory CD8+ T cells and soluble 4-1BB

Increase of effector memory CD8+ T cells and soluble 4-1BB
Increase of effector memory CD8+ T cells and soluble 4-1BB

Posters

좌우스크롤
Posters(Pipeline, Name, Title, PDF)
Pipeline Name Title PDF
ABL111 SITC TJ-CD4B (ABL111), a Claudin18.2-targeted 4-1BB tumor engager induces potent tumordependent immune response without dose-limiting toxicity in preclinical studies PDF 아이콘
AACR 2020 Claudin 18.2 x 4-1BB bispecific antibody induced potent tumor inhibition through tumor-specific 4-1BB activation PDF 아이콘

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ABL301

  • Pipeline
    ABL301
  • Program Target
    SNCA x IGF1R
  • Disease Indication
    Parkinson’s Disease
  • Development Stage
    IND enabling study
Summary
The propagation of aggregated forms of alpha-synuclein (α-synuclein, SNCA) appears to be critical for the etiology of Parkinson’s disease and multiple system atrophy. ABL301 selectively targets aggregated forms of α-syn as a potential disease target, avoiding those of its normal, monomeric form. Since poor delivery of antibodies past the blood-brain-barrier is thought to be one of the major obstacles for CNS-related drug development, ABL301 also has a shuttle antibody that allows for improved delivery of antibody therapeutics into the brain. This dual mechanism will enable antibody therapeutics to more efficiently reach their targets, leading to better therapeutic efficacy compared to conventional monoclonal antibodies.
Figure from biopharmadeal makers (2017)
좌우스크롤 Figure from biopharmadeal makers (2017)

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ABL501

  • Pipeline
    ABL501
  • Program Target
    PD-L1 x LAG-3
  • Disease Indication
    Solid Tumor
  • Development Stage
    Clinical Development
    (Phase 1)
Summary
ABL501 is a bispecific antibody capable of blocking the PD-L1 and LAG-3 immune checkpoint pathways, overcoming the current limitations of conventional PD-(L)1 therapy based around resistance to PD-L1 and low response rates. ABL501 demonstrates a higher efficacy over LAG-3 alone, PD-L1 alone, and the combination of LAG-3 and PD-L1, and shows superior performance compared to competing substances.

Mechanism of action

ABL501 is a bispecific antibody targeting LAG-3 and PD-L1 and blocks the interaction of LAG3-MHCII and PD-1-PD-L1,
releasing T cells from tumor-mediated suppression

Mechanism of action
좌우스크롤 Mechanism of action

Higher T cell activation than combination of LAG-3 and PD-L1 antibodies

ABL501 induced superior T cell activation compared to the combination of LAG-3 and PD-L1 antibodies as indicated in PBMC-based IL-2 expression assays and dual blockade reporter assays

Strong tumor killing effect of ABL501 compared with Atezolizumab

ABL501 induced stronger cytotoxic activity on NSCLC cells in the presence of tumor-matched patient PBMCs

Potent inhibition on tumor progression

ABL501 exhibited dose-dependent tumor growth inhibition

Phase 1 clinical study

Monotherapy dose escalation is ongoing with support of Korea Drug Development Fund funded by Ministry of Science and ICT, Ministry of Trade, Industry, and Energy, and Ministry of Health and Welfare (HN21C0979000021, Republic of Korea).

Posters

좌우스크롤
Posters(Pipeline, Name, Title, PDF)
Pipeline Name Title PDF
ABL501 AACR ABL501 (PD-L1xLAG-3), a bispecific antibody promotes enhanced human T cell activation through targeting simultaneously two immune checkpoint inhibitors, LAG-3 and PD-L1 PDF 아이콘

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ABL503

  • Pipeline
    ABL503
  • Program Target
    PD-L1 x 4-1BB
  • Disease Indication
    Solid Tumor
  • Development Stage
    Clinical Development
    (Phase 1)
Summary
ABL503 is a bispecific antibody that combines the capabilities of PD-L1 checkpoint pathway inhibiton with 4-1BB agonistic activity to overcome the specific limitations of PD-(L)1 immunotherapy and 4-1BB related toxicity. ABL503 is uniquely designed to only induce 4-1BB signalling when simultaneously binded to the PD-L1 tumor antigen on cancer cells, limiting the toxicity characteristic of traditional 4-1BB based treatment while augmenting T-cell activation. ABL503 shows superior anti-tumor activity in an animal model system compared to PD-L1 alone, 4-1BB alone, and the combination of PD-L1 and 4-1BB, with immunological memory resistant to any possible recurrence of the tumor.

Structure and Mechanism of Action

Structure and Mechanism of Action
좌우스크롤 Structure and Mechanism of Action

PD-L1 Dependent 4-1BB Activation

PD-L1 Dependent 4-1BB Activation
PD-L1 Dependent 4-1BB Activation

Superior Anti-Tumor Effect with Immunological Memory

Superior Anti-Tumor Effect with Immunological Memory
Superior Anti-Tumor Effect with Immunological Memory

Pharmacodynamic changes along with anti-tumor effect

Pharmacodynamic changes along with anti-tumor effect
Pharmacodynamic changes along with anti-tumor effect

Superior activity over Atezolizumab

Superior activity over Atezolizumab
Superior activity over Atezolizumab

Publications

좌우스크롤
Publications(Pipeline, Journal, Date, Title, Link, PDF)
Pipeline Journal Date Title Link PDF
ABL503 JITC 2021 Novel anti-4-1BB×PD-L1 bispecific antibody augments anti-tumor immunity through tumor-directed T-cell activation and checkpoint blockade 링크정보 아이콘 PDF 아이콘

Posters

좌우스크롤
Posters(Pipeline, Name, Title, PDF)
Pipeline Name Title PDF
ABL503 SITC ABL503 (TJ-L14B), PD-L1×4-1BB bispecific antibody, induces superior anti-tumor activity by PD-L1-dependent 4-1BB activation with the increase of 4-1BB+CD8 + T cells in tumor microenvironment PDF 아이콘
PEGS 2019 The PD-L1 x 4-1BB Bispecific Antibody ABL503 Shows Potent Anti-Tumor Effect through Tumor-Directed T Cell Activation PDF 아이콘

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ABL101

  • Pipeline
    ABL101
  • Program Target
    BCMAx4-1BB
  • Disease Indication
    Hematologic Cancer
  • Development Stage
    IND enabling study
Summary
A novel T-cell engaging bispecific antibody, ABL101 demonstrates a robust anti-tumor effect via BCMA mediated 4-1BB activation in tumor microenvironments (TME). ABL101 only activates 4-1BB signaling pathways in the presence of BCMA expressing cancer cells, minimizing the probability of hepatotoxicity in healthy tissues. ABL101 inhibits tumor growth and, by retaining immunological memory, induces a prolonged anti-tumor effect.

Structure and Mechanism of Action

Structure and Mechanism of Action
Structure and Mechanism of Action

BCMA Dependent 4-1BB Activation

ABL101 activates 4-1BB signaling only in the presence of tumor cells In a BCMA expression-dependent manner

BCMA Dependent 4-1BB Activation
BCMA Dependent 4-1BB Activation

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ABL103

  • Pipeline
    ABL103
  • Program Target
    B7-H4x4-1BB
  • Disease Indication
    Solid Cancer
  • Development Stage
    IND enabling study
Summary
A novel T-cell engaging bispecific antibody, ABL103 demonstrates efficacious anti-tumor activity via B7-H4 mediated 4-1BB activation in tumor microenvironments (TME), only activating 4-1BB signaling pathways when in the presence of B7-H4 expressing cells. ABL103 strongly inhibits tumor growth and induces immunological memory to create prolonged anti-tumor protection.

Structure and Mechanism of Action

Structure and Mechanism of Action
Structure and Mechanism of Action

B7-H4 Dependent 4-1BB Activation

ABL103 induces more significant cell lysis than Urelumab with B7-H4 dependent 4-1BB activation

BCMA Dependent 4-1BB Activation
BCMA Dependent 4-1BB Activation

Superior Anti-Tumor Effect with Immunological Memory

ABL103 Completely eliminates tumors in advanced tumor model and protects mice from re-challenge with MC38-B7-H4 tumor

Superior Anti-Tumor Effect with Immunological Memory
좌우스크롤 Superior Anti-Tumor Effect with Immunological Memory

Posters

좌우스크롤
Posters(Pipeline, Name, Title, PDF)
Pipeline Name Title PDF
ABL103 AACR 2022 A novel T-cell engaging bispecific antibody, exhibits potent in vitro and vivoantitumor activity and low toxicity via B7-H4 dependent 4-1BB activation in tumor microenvironment PDF 아이콘
PEGS Europe A novel T-cell engaging bispecific antibody, ABL103, shows potent anti-tumor effect via B7-H4 mediated 4-1BB activation in TME PDF 아이콘

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