A Phase 1 Dose Escalation and Expansion Study of ABL103, a Bispecific Antibody of 4-1BB and B7-H4, as a Single Agent in Subjects With Any Progressive Locally Advanced or Metastatic Solid Tumors

This is a first-in-human Phase 1, single-arm, open-label, multicenter, multiple-dose, dose-escalation study of ABL103 to evaluate the safety, tolerability, MTD (maximum tolerated dose) and/or RP2D (recommended phase 2 dose), pharmacokinetics, immunogenicity, preliminary antitumor activity of ABL103 in subjects with any progressive locally advanced(unresectable) or metastatic solid tumor who are relapsed or refractory following the last line of treatment and have no available standard of care option. This study includes 2 parts: a dose-escalation part and tumor-expansion part

Start Date07 Nov 2023

Sponsor / Collaborator

ABL Bio, Inc.

NCT05756920 / RecruitingPhase 1

A Phase 1 Randomized, A Phase 1 Randomized, Placebo Controlled, Double Blind, Two Part, Single- and Multiple-Ascending-Dose Trial to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Intravenously Administered ABL301 in Healthy Adult Participants

This is a Phase 1, FIH, randomized, double-blind, placebo-controlled study designed to assess the safety, tolerability, PK and PD after SAD and MAD in healthy adult participants.

Start Date31 Dec 2022

Sponsor / Collaborator

ABL Bio, Inc.

NCT05101109 / CompletedPhase 1

A Phase 1 Dose Escalation and Expansion Study of ABL501, a Bispecific Antibody of PD-L1 and LAG-3 as a Single Agent in Subjects With Any Progressive, Locally Advanced (Unresectable) or Metastatic Solid Tumors

This is a first-in-human (FIH) phase 1 open-label, multicenter, multiple-dose, dose-escalation and dose-expansion study of ABL501 to evaluate the safety, tolerability, MTD and/or RP2D, PK, immunogenicity, preliminary anti-tumor activity, and the PD effect of ABL501 in subjects with any progressive locally advanced (unresectable) or metastatic solid tumors. This study included 2 parts; a dose-escalation part and a dose expansion part.

Start Date06 Oct 2021

Sponsor / Collaborator

ABL Bio, Inc.

100 Clinical Results associated with ABL Bio, Inc.

0 Patents (Medical) associated with ABL Bio, Inc.

Literatures (Medical) associated with ABL Bio, Inc.

13 Sep 2024·Clinical Cancer Research

Anti–4-1BB×PDL1 Bispecific Antibody Reinvigorates Tumor-Specific Exhausted CD8+ T Cells and Enhances the Efficacy of Anti-PD1 Blockade

Article

Author: Han, Dai Hoon ; Jeon, Jaehyoung ; Kim, Youngkwang ; Jeong, Da Som ; Lee, Jung-Yun ; Jeon, Seung Hyuck ; Chung, Youseung ; Kim, Hyunjoo ; Son, Woo-Chan ; You, Gihoon ; Jung, Jaeho ; Park, Junsik ; Shin, Eui-Cheol ; Park, Su-Hyung ; Park, Kyungjin

AbstractPurpose:To overcome the limited efficacy of immune checkpoint blockade, there is a need to find novel cancer immunotherapeutic strategies for the optimal treatment of cancer. The novel anti–4-1BB×PDL1 bispecific antibody—ABL503 (also known as TJ-L14B)—was designed to simultaneously target PDL1 and 4-1BB and demonstrated strong antitumor T-cell responses without considerable toxicity. In this study, we investigated the mechanisms by which the combination of ABL503 and anti-PD1 blockade affected the reinvigoration of exhausted tumor-infiltrating CD8+ T cells (CD8+ TIL) and antitumor efficacy.Experimental Design:Single-cell suspensions of hepatocellular carcinoma and ovarian cancer tissues from treatment-naïve patients were used for immunophenotyping of CD8+ TILs and in vitro functional assays. Humanized hPD1/hPDL1/h4-1BB triple–knock-in mice were used to evaluate the effects of ABL503 and anti-PD1 blockade in vivo.Results:We observed that ABL503 successfully restored the functions of 4-1BB+ exhausted CD8+ TILs, which were enriched for tumor-specific T cells but unresponsive to anti-PD1 blockade. Importantly, compared with anti-PD1 blockade alone, the combination of ABL503 and anti-PD1 blockade further enhanced the functional restoration of human CD8+ TILs in vitro. Consistently, the combination of ABL503 with anti-PD1 in vivo significantly alleviated tumor growth and induced enhanced infiltration and activation of CD8+ TILs.Conclusions:ABL503, a PDL1 and 4-1BB dual-targeting bispecific antibody, elicits pronounced additive tumor growth inhibition, with increased infiltration and functionality of exhausted CD8+ T cells, which in turn enhances the anticancer effects of anti-PD1 blockade. These promising findings suggest that ABL503 (TJ-L14B) in combination with PD1 inhibitors will likely further enhance therapeutic benefit in clinical trials.See related commentary by Molero-Glez et al., p. 3971

22 Mar 2024·Cancer Research

Abstract 5304: ABL407, a LILRB4x4-1BB bispecific antibody with a wild type Fc, exhibits potent antitumor activity by modulating immune system in multiple ways involving T cells, myeloids, and regulatory T cells

Author: Kim, Sora ; Park, Kyungjin ; Youn, Hyunseong ; Lee, Yangsoon ; Park, Yelim ; Seon, Minkyu ; Won, Jonghwa

AbstractTumor-associated myeloid cells such as myeloid-derived suppressor cells (MDSC) accumulate in the tumor microenvironment (TME) and suppress anti-tumor immune responses in a broad range of cancers. LILRB4 (Leukocyte Immunoglobulin-Like Receptor Subfamily B Member 4), an emerging myeloid target, is specifically expressed in tumor-associated myeloid cells and suppresses the immune response, thus promoting cancer progression and metastasis. ABL407 is a First-in-Class bispecific antibody designed to simultaneously target LILRB4 and 4-1BB, enabling LILRB4 expression-dependent 4-1BB activation. By antagonizing LILRB4 signaling, ABL407 inhibited LILRB4 mediated immunosuppression, restoring T cell activity. In addition, ABL407 inhibited fibronectin, a potential LILRB4 ligand, -mediated suppression of myeloid cells. To evaluate the efficacy of ABL407, we established EL4 murine tumor model overexpressing LILRB4 (EL4/LILRB4) in h4-1BB transgenic mice and hLILRB1/4-h4-1BB triple transgenic mice. We observed LILRB4 was overexpressed in M-MDSC in the blood and liver-metastasized tumors. A significant decrease of M-MDSC population and tumor growth inhibition was observed in mice treated with anti-LILRB4 antibody and ABL407. ABL407 treatment resulted in a proportion increment of T cells. However, the percentage of Treg cells and M-MDSC in the liver and blood was reduced by ABL407 treatment in hLILRB1/4-h4-1BB triple transgenic mice. Mice with complete remission (CR) were further protected from the rechallenge of previously exposed tumor after 3 months of cessation of ABL407 treatment, implicating that immunological memory might be generated. In conclusion, our findings suggest that ABL407, LILRB4x4-1BB bispecific antibody, may be a promising strategy for the treatment of cancer. It can be applied as a "LILRB4 antagonist" as well as a "LILRB4-dependent 4-1BB agonist" across a broad spectrum of cancers.Citation Format: Minkyu Seon, Yangsoon Lee, Hyunseong Youn, Yelim Park, Sora Kim, Kyungjin Park, Jonghwa Won. ABL407, a LILRB4x4-1BB bispecific antibody with a wild type Fc, exhibits potent antitumor activity by modulating immune system in multiple ways involving T cells, myeloids, and regulatory T cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5304.

22 Mar 2024·Cancer Research

Abstract 5303: A novel TIGIT and 4-1BB bispecific antibody, ABL112, exhibits potent in vitro and in vivo antitumor activity through dual immune modulation

Author: Lee, Yangsoon ; Won, Jonghwa ; Son, Wonjun ; Park, Yelim

AbstractT cell immunoreceptor with Ig and ITIM domains (TIGIT) is an immune checkpoint molecule responsible for delivering inhibitory signals that suppress immune activation. Due to its inhibitory role in the immune response, TIGIT has emerged as a potential therapeutic target for various malignancies, with several clinical trials exploring the use of anti-TIGIT blocking antibodies with anti-PD-(L)1 therapies. Recent reports have indicated elevated expression of 4-1BB within intra-tumoral Tregs. Therefore, we hypothesized that a dual targeting approach involving both TIGIT and 4-1BB could effectively enhance intra-tumoral immunity.ABL112, a First-in-Class bispecific antibody targeting TIGIT and 4-1BB, demonstrated the induction of T cell activation by blocking the TIGIT signaling and TIGIT dependent 4-1BB clustering. By having intact Fc, ABL112 bound to FcγRI and its crosslinking with 4-1BB also induced 4-1BB activation. ABL112 selectively depleted Treg cells but not other T cells in vitro, potentially through antibody-dependent cell-mediated cytotoxicity.ABL112 demonstrated superior efficacy in tumor regression compared to anti-TIGIT monoclonal antibody across various mouse tumor models. Additionally, combining ABL112 with pembrolizumab significantly inhibited tumor growth better than combining anti-TIGIT monoclonal antibody with pembrolizumab. According to immune cell depletion assay, ABL112-mediated tumor suppressive activity was predominantly driven by CD8+ T cells, with a partial tumor reduction by CD4+ T cell or NK cell depletion. Mice with complete remission (CR) were further protected from the tumor re-challenge after 3 months of cessation of ABL112 treatment, and the proportion of tumor-specific memory T cells in the blood increased, suggesting long-term immunological memory has been established. In conclusion, ABL112 exhibited potent in vitro and in vivo anti-tumor activity through multiple mode of action including TIGIT inhibition and 4-1BB activation. These results strongly suggest that ABL112 is an innovative and promising therapeutic option with the combination of anti-PD-(L)1 therapies for cancer patients.Citation Format: Wonjun Son, Yangsoon Lee, Yelim Park, Jonghwa Won. A novel TIGIT and 4-1BB bispecific antibody, ABL112, exhibits potent in vitro and in vivo antitumor activity through dual immune modulation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5303.

News (Medical) associated with ABL Bio, Inc.

30 Oct 2024

·www.prnewswire.com

I-Mab to Present Givastomig Phase 1 Optimal Dose Estimation Data at SITC 2024

- Poster to be presented in a late-breaking abstract session at the Society for Immunotherapy of Cancer (SITC) on Saturday, November 9, 2024 ROCKVILLE, Md., Oct. 30, 2024 /PRNewswire/ -- I-Mab (NASDAQ: IMAB) (the "Company"), a U.S.-based, global biotech company exclusively focused on the development of highly differentiated immunotherapies for the treatment of cancer, today announced the presentation of a poster highlighting Phase 1 optimized dose estimation data for givastomig monotherapy (TJ033721/ABL111), a novel first-in-class Claudin18.2 (CLDN18.2) and 4-1BB bispecific antibody, at SITC 2024. The conference is being held in Houston, Texas, from November 6-10, 2024. Presentation Details: Title: Optimal dose estimation using an integrated approach from Phase I data of givastomig, a novel Claudin18.2×4-1BB bispecific antibody Poster #: 1474 Presenter: J.A. Yanez, I-Mab Session: Poster Hall, George R. Brown Convention Center Session Date: Saturday, November 9, 2024 Session Time: 9:00 am CDT to 8:30 pm CDT, Level 1 – Exhibit Halls AB A full copy of the poster will be available on the I-Mab website under the "Innovation, Publications & Presentations" tab on November 9, 2024. About Givastomig Givastomig (TJ033721 / ABL111) is a bispecific antibody targeting Claudin (CLDN) 18.2-positive tumor cells. It conditionally activates T cells through the 4-1BB pathway in the tumor microenvironment where CLDN18.2 is expressed. Givastomig appears to maintain strong tumor binding and anti-tumor activity, attributable to a synergistic effect of proximal interaction with CLDN18.2 and 4-1BB, while minimizing liver toxicity and systemic immunotoxicity commonly seen with other emerging 4-1BB-based product candidates. In March 2022, the U.S. Food and Drug Administration (FDA) granted Orphan Drug Designation for givastomig for the treatment of gastric cancer, including cancer of the gastroesophageal junction. A Phase 1b study is ongoing evaluating givastomig, in combination with standard-of-care nivolumab plus chemotherapy, in treatment-naïve patients with gastric cancers, including gastroesophageal cancer (NCT04900818). The program is being jointly developed through a global partnership with ABL Bio, in which I-Mab is the lead party and shares worldwide rights, excluding China and South Korea, equally with ABL Bio. About I-Mab I-Mab (NASDAQ: IMAB) is a U.S.-based, global biotech company exclusively focused on the development of highly differentiated immunotherapies for the treatment of cancer. I-Mab has established operations in Rockville, Maryland, and Short Hills, New Jersey. For more information, please visit and follow us on LinkedIn and X. I-Mab Investor & Media Contacts Tyler Ehler Senior Director, Investor Relations [email protected] SOURCE I-Mab Biopharma WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

ImmunotherapyPhase 1Orphan DrugAACRASCO

04 Oct 2024

·pipelinereview.com

ABL Bio Announces Clinical Collaboration to Evaluate ABL103 in Combination with KEYTRUDA® (pembrolizumab) in Patients with Solid Tumors

– MSD will supply KEYTRUDA to be evaluated in combination with ABL Bio’s ABL103 in a Phase 1b/2 clinical trial SEONGNAM, South Korea I October 4, 2024 I ABL Bio (CEO Sang Hoon Lee), a company specializing in bispecific antibodies, today announced that it has entered into a clinical trial collaboration and supply agreement with MSD (a subsidiary of Merck & Co., Inc., Rahway, NJ, USA), to evaluate ABL103 in combination with MSD’s anti-PD-1 therapy, KEYTRUDA ® (pembrolizumab) in patients with advanced or metastatic solid tumors. Under the terms of the agreement, ABL Bio will conduct a phase 1b/2 clinical trial to evaluate the safety and efficacy of ABL103 in combination with KEYTRUDA. In this combination study, MSD will supply KEYTRUDA. ABL103 is bispecific antibody that simultaneously targets B7-H4 and 4-1BB. ABL103 is one of the pipeline programs in which ABL Bio’s 4-1BB based bispecific antibody platform ‘Grabody-T’ has been applied. Grabody-T is designed to activate T cells only in the tumor microenvironment, reducing the liver toxicity of conventional 4-1BB monoclonal antibody and enhancing the antitumor activity. ABL103 also has mechanism to activate the 4-1BB signaling pathways in the tumor microenvironments where the B7-H4 antigens exist, allowing T cells to selectively attack tumor cells while sparing normal cells. Currently, the dose escalation part of the phase 1 clinical trial for ABL103 is ongoing in South Korea. Sang Hoon Lee, CEO of ABL Bio said “we are pleased to enter into this clinical collaboration agreement with MSD. With this agreement, we are ready to move on to the next stage of ABL103 clinical development. We hope that the combination of ABL103 and KEYTRUDA contributes to a better life for patients with advanced or metastatic solid tumors. To date, the phase 1 study for ABL103 monotherapy is progressing smoothly, and we will do our best in clinical development to achieve meaningful results from ABL103.” Meanwhile, ABL Bio is developing various clinical and non-clinical assets based on its bispecific antibody platform ‘Grabody’. More than 15 clinical projects for more than 7 assets, including ABL001, ABL111, ABL503, ABL105, ABL202, ABL301, and ABL103, are underway for different indications in various countries, including the United States, China, Australia, and Korea. In the case of ABL001, the U.S. Food and Drug Administration (FDA) recently granted Fast Track designation to support the rapid development of this new drug candidate. Meanwhile, ABL Bio is preparing to initiate clinical trials for ABL104. In addition, ABL Bio is continuously researching and developing several other product candidates, including bispecific antibody-drug conjugates (ADCs). KEYTRUDA ® is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. SOURCE: ABL Bio

Phase 1License out/inFast TrackADC

04 Oct 2024

·www.prnewswire.com

ABL Bio Announces Clinical Collaboration to Evaluate ABL103 in Combination with KEYTRUDA® (pembrolizumab) in Patients with Solid Tumors

- MSD will supply KEYTRUDA to be evaluated in combination with ABL Bio's ABL103 in a Phase 1b/2 clinical trial SEONGNAM, South Korea, Oct. 4, 2024 /PRNewswire/ -- ABL Bio (CEO Sang Hoon Lee), a company specializing in bispecific antibodies, today announced that it has entered into a clinical trial collaboration and supply agreement with MSD (a subsidiary of Merck & Co., Inc., Rahway, NJ, USA), to evaluate ABL103 in combination with MSD's anti-PD-1 therapy, KEYTRUDA® (pembrolizumab) in patients with advanced or metastatic solid tumors. Under the terms of the agreement, ABL Bio will conduct a phase 1b/2 clinical trial to evaluate the safety and efficacy of ABL103 in combination with KEYTRUDA. In this combination study, MSD will supply KEYTRUDA. ABL103 is bispecific antibody that simultaneously targets B7-H4 and 4-1BB. ABL103 is one of the pipeline programs in which ABL Bio's 4-1BB based bispecific antibody platform 'Grabody-T' has been applied. Grabody-T is designed to activate T cells only in the tumor microenvironment, reducing the liver toxicity of conventional 4-1BB monoclonal antibody and enhancing the antitumor activity. ABL103 also has mechanism to activate the 4-1BB signaling pathways in the tumor microenvironments where the B7-H4 antigens exist, allowing T cells to selectively attack tumor cells while sparing normal cells. Currently, the dose escalation part of the phase 1 clinical trial for ABL103 is ongoing in South Korea. Sang Hoon Lee, CEO of ABL Bio said "we are pleased to enter into this clinical collaboration agreement with MSD. With this agreement, we are ready to move on to the next stage of ABL103 clinical development. We hope that the combination of ABL103 and KEYTRUDA contributes to a better life for patients with advanced or metastatic solid tumors. To date, the phase 1 study for ABL103 monotherapy is progressing smoothly, and we will do our best in clinical development to achieve meaningful results from ABL103." Meanwhile, ABL Bio is developing various clinical and non-clinical assets based on its bispecific antibody platform 'Grabody'. More than 15 clinical projects for more than 7 assets, including ABL001, ABL111, ABL503, ABL105, ABL202, ABL301, and ABL103, are underway for different indications in various countries, including the United States, China, Australia, and Korea. In the case of ABL001, the U.S. Food and Drug Administration (FDA) recently granted Fast Track designation to support the rapid development of this new drug candidate. Meanwhile, ABL Bio is preparing to initiate clinical trials for ABL104. In addition, ABL Bio is continuously researching and developing several other product candidates, including bispecific antibody-drug conjugates (ADCs). KEYTRUDA® is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. SOURCE ABL Bio, Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Phase 1License out/inFast Track

100 Deals associated with ABL Bio, Inc.

100 Translational Medicine associated with ABL Bio, Inc.

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The statistics for drugs in the Pipeline is the current organization and its subsidiaries are counted as organizations,Early Phase 1 is incorporated into Phase 1, Phase 1/2 is incorporated into phase 2, and phase 2/3 is incorporated into phase 3

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Drug(Targets)	Indications	Global Highest Phase

TR-009 ( DLL4 x VEGF-A )	Biliary Tract Neoplasms More	Phase 3 Clinical
ABL-501 ( LAG3 x PDL1 )	Advanced Malignant Solid Neoplasm More	Phase 1
ABL-301 ( IGF-1R x α-synuclein )	-	Phase 1
LCB-71 ( ROR1 )	Hematologic Neoplasms More	Phase 1
Ragistomig ( 4-1BB x PDL1 )	Advanced Malignant Solid Neoplasm More	Phase 1

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