ADG153 / Adagene - LARVOL DELTA

ADG153, a novel masked anti-CD47 IgG1 SAFEbody, demonstrates strong in vivo anti-tumor activities in preclinical solid tumor models and preferential CD47 target engagement in the tumor microenvironment (AACR 2023) - "In normal tissues, the SAFEbody masking moiety is expected to shield ADG153 from binding to CD47; however, in the presence of highly upregulated CD47 in protease-rich tumor microenvironment (TME), the masked antibody can engage dynamically with highly expressed CD47 and can be cleaved, enabling efficient binding to CD47, blocking CD47/SIRPα signaling, and triggering strong anti-tumor activities in solid tumors. The in vivo anti-tumor efficacy of ADG153 or magrolimab analog (magrolimab) was assessed across several solid tumor xenograft models. ADG153 demonstrates significantly reduced antigen sink liabilities and favorable CD47 engagement in the TME, which are highly differentiated from other anti-CD47 agents. ADG153 is locally enriched and efficiently cleaved in tumors, engages its target, and elicits potent anti-tumor activities in multiple solid tumor xenograft models. These results indicate that the ADG153 SAFEbody is a novel anti-CD47 IgG1 antibody prodrug with..."

Preclinical • Tumor microenvironment • Gastric Cancer • Gastrointestinal Cancer • Lung Cancer • Neuroendocrine Tumor • Oncology • Ovarian Cancer • Small Cell Lung Cancer • Solid Tumor • Triple Negative Breast Cancer • CD47 • SIRPA

Adagene Presents Clinical Data for Anti-CTLA-4 SAFEbody ADG126 Reinforcing Best-in-Class Safety Profile at Repeat Doses and Showing Early Efficacy Profile in Advanced/Metastatic Solid Tumors (GlobeNewswire) - "A third poster...reported preclinical data for ADG153. The data demonstrated strong in vivo anti-tumor activities in solid tumor models and a robust safety profile due to preferential CD47 target engagement in the tumor microenvironment."

Preclinical • Oncology • Solid Tumor

Adagene Announces Poster Presentations on Anti-CTLA-4 SAFEbody, ADG126, at Upcoming American Association for Cancer Research (AACR) Annual Meeting in April (GlobeNewswire) - "Adagene...announced poster presentations at the upcoming AACR Annual Meeting in Orlando, Florida from April 14-19, 2023. Two poster presentations on ADG126 SAFEbody will report results of ongoing phase 1b/2 trials of this masked, anti-CTLA-4 therapy in combination with two different anti-PD-1 treatments at multiple dosing regimens (6 mg/kg and 10 mg/kg)....The third poster will review the differentiated preclinical profile of ADG153, an anti-CD47 SAFEbody® in IgG1 isotype, currently in the IND-enabling stage."

P1/2 data • Preclinical • Oncology • Solid Tumor

Adagene Reports Financial Results for the Six Months Ended June 30, 2022 and Provides Corporate Updates (GlobeNewswire) - "UPDATED MILESTONES & OUTLOOK: 2023: (i) Initiate patient dosing in ADG206 phase 1 trial; (ii) Submit IND or equivalent for ADG153, and initiate phase 1 trial; (iii) Results from IIT combination studies of ADG106; (iv) Additional collaborations and/or technology licensing agreements."

IND • Licensing / partnership • New P1 trial • Oncology

ADG153-G1, a highly differentiated anti-CD47 IgG1 SAFEbody, demonstrates potent in vivo anti-tumor activities with enhanced ADCC/ADCP effects and significantly reduced RBC-related and antigen sink liabilities (AACR 2022) - "Next, our SAFEbody® technology for precision masking enables us to mask the CD47 binding sites to create the masked antibody in active IgG1 isotype called ADG153-G1 SAFEbody, which can be conditionally activated to bind and inhibit CD47 on tumor cells for potent tumor killing with much improved safety and pharmacokinetic profiles.In vitro studies showed that the activated ADG153-G1 SAFEbody blocked CD47 binding to SIRPα, bound to the CD47 protein, CD47+ tumor cell lines, and human RBCs, and induced strong ADCC/ADCP activities. Consistent with a reduced antigen sink effect due to lower RBC binding, the ADG153-G1 SAFEbody had more favorable pharmacokinetic properties than the Hu5F9 analog (~8× longer t1/2 and ~5× higher AUC) at 10 mg/kg. Taken together, these results indicate that the ADG153-G1 SAFEbody is a differentiated anti-CD47 IgG1 antibody prodrug with strong ADCC/ADCP potential and significantly reduced anemia-related and antigen sink liabilities,..."

Preclinical • Hematological Malignancies • Oncology • SIRPA

Adagene Presents Data Demonstrating First and Best-in-Class Potential for Differentiated Preclinical Antibody Candidates at American Association for Cancer Research (AACR) Annual Meeting 2022 (GlobeNewswire) - "Preclinical data demonstrated that ADG153 IgG1 was well tolerated, did not induce human hemagglutination and significantly reduced anemia-related and antigen sink liabilities. In particular, ADG153 IgG1 at a 10 mg/kg dose demonstrated only an 8 percent decrease in red blood cell counts, compared to a 49 percent decrease with a benchmark antibody which is in IgG4 format (analogue of magrolimab)....Adagene is preparing to submit an IND or equivalent filing for ADG153 during 2022....Preclinical data demonstrated the excellent safety profile of ADG138, including 100-fold greater reduction in cytokine release compared to its parental TCE."

IND • Preclinical • Hematological Malignancies • Oncology • Solid Tumor

Adagene Announces Four Poster Presentations on Robust Preclinical Pipeline of Antibody-Based Therapeutics at Upcoming American Association for Cancer Research (AACR) Annual Meeting (GlobeNewswire) - "Adagene Inc...announced publication of four abstracts featuring preclinical data from its expanding pipeline in advance of the AACR Annual Meeting 2022 in New Orleans, Louisiana from April 8-13, 2022. The full abstracts are available on the AACR meeting website. At AACR, presentations will include preclinical results showing the potential best-in-class profiles for three differentiated preclinical product candidates in IND-enabling studies: ADG138, ADG206 and ADG153. The fourth presentation introduces a new capability for the company’s proprietary bispecific T-cell engagers (TCEs) with CD28."

Preclinical • Oncology • Solid Tumor

ADG153, an Anti-CD47 Monoclonal Antibody Prodrug, Has Strong In Vivo Anti-Tumor Activity, Minimal RBC-Related and Antigen Sink Liabilities, and Extended Half Life in Comparison with Benchmark Clinical Antibodies of the Same IgG Subclass (ASH 2021) - "Blocking CD47 on RBCs, such as by magrolimab (Hu5F9), has led to transient anemia, requiring step-up dosing in the clinic. Collectively, ADG153 SAFEbody is a differentiated anti-CD47 antibody that has strong in vivo anti-tumor activity with reduced RBC-related and antigen sink liabilities and favorable PK properties. This preclinical profile with an enhanced therapeutic index provides a strong rationale for advancing ADG153 SAFEbody into clinical development."

Preclinical • Anemia • Hematological Disorders • Hematological Malignancies • Oncology • CD47 • SIRPA

Adagene Presents Preclinical Data Showcasing Best-in-Class Profiles for ADG153, an Anti-CD47 SAFEbody and ADG152, a CD20xCD3 Bispecific T-cell Engager POWERbody (GlobeNewswire) - "Adagene...today announced preclinical data demonstrating the compelling differentiation of ADG153, an anti-CD47 monoclonal antibody (mAb), and ADG152, a CD20xCD3 bispecific T-cell engager (TCE)....Preclinical results concluded that the ADG153-G1 can achieve potent anti-CD47 efficacy with a well-tolerated safety profile, providing a strong rationale to advance this candidate into clinic. Currently, no other known anti-CD47 antibodies using the IgG1 isotype are in clinical development....In preclinical models, ADG152 resulted in dose-dependent anti-tumor activity with almost complete tumor growth inhibition when dosed at 1.5 mg/kg....ADG152 also demonstrated improved pharmacokinetics in monkeys versus the plamotamab analog, with approximately a 2-fold longer half-life (7-13 days at 0.3 - 30mg/kg) and approximately an 8-fold higher AUC after a single intravenous injection."

Preclinical • Hematological Malignancies • Oncology