ADG116 / Adagene - LARVOL DELTA

Deciphering improved clinical therapeutic index (TI) of Muzastotug (ADG126), a masked anti-CTLA-4 SAFEbody® over its unmasked form (ADG116) as monotherapy or in combination with anti-PD-1 therapy (SITC 2024) - "ADG116, an IgG1 monoclonal antibody targeting a unique epitope of CTLA-4 which is conserved across species, has demonstrated improved TI over ipilimumab via enhanced epitope-dependent ADCC and T cell priming...When combined with toripalimab, muzastotug at 10 mg/kg Q3W showed significantly better safety and similar efficacy versus ADG116 at 3 mg/kg Q6W (highest tolerable regimen)...Modeling predicts a significantly higher and sustained SS tumor-specific engagement of CTLA-4 by muzastotug in patients. The potential best-in-class profile of muzastotug supports further clinical development.1"

Clinical • Combination therapy • IO biomarker • Monotherapy • Oncology • IFNG

ADG116-1003: A Phase 1b/2 Study of ADG116, ADG116 Combined With Anti-PD-1 Antibody or Anti-CD137 Antibody in Solid Tumors Patients (clinicaltrials.gov) - P1 | N=72 | Active, not recruiting | Sponsor: Adagene Inc | Trial completion date: Aug 2024 ➔ Feb 2025 | Trial primary completion date: Jul 2024 ➔ Jan 2024

Metastases • Trial completion date • Trial primary completion date • Oncology • Solid Tumor

Adagene Announces Clinical Data at SITC 2022 on Anti-CTLA-4 NEObody, ADG116, Showing Differentiated Safety and Anti-tumor Activity in Heavily Pre-treated Patients with Difficult-to-Treat Tumors (GlobeNewswire) - P1 | N=204 | NCT04501276 | Sponsor: Adagene | "Adagene...announced clinical data from phase 1b/2 studies of its anti-CTLA-4 antibody candidate, ADG116, in two poster presentations at the Society for Immunotherapy of Cancer’s (SITC) Annual Meeting taking place in Boston....The safety and preliminary efficacy readout included patients with over 20 different tumor types, the majority (64%) of whom received three or more lines of prior therapies and over one third (36%) of whom progressed from prior immuno-oncology (IO) therapy. Combination data from dose escalation of ADG116 plus the anti-PD-1 therapy, toripalimab, were also reported from nine heavily pre-treated patients, close to half (44%) of whom received three or more lines of prior therapy."

P1 data • Oncology • Solid Tumor

Adagene Reports Full Year 2023 Financial Results and Provides Corporate Update (GlobeNewswire) - P1b/2 | N=72 | NCT04501276 | Sponsor: Adagene Inc | "Phase 1b/2 data for ADG116....showed a favorable safety profile and clinical responses, both in monotherapy and in combination with anti-PD-1: ADG116 monotherapy has demonstrated a favorable safety profile at doses up to 15 mg/kg (N=59) and an overall response rate (ORR) of 13% (3/23 evaluable), including confirmed and durable PRs in multiple tumor types; In combination with anti-PD-1 therapy, ADG116 (3 mg/kg Q6W) (N=22) showed a manageable safety profile and an encouraging efficacy profile in dose escalation. Clinical responses from the combination cohorts include a complete response (CR) sustained for nearly two years in a head and neck squamous cell carcinoma (HNSCC) patient dosed with repeat cycles of ADG116 3 mg/kg (initially every three weeks, then every six weeks) plus toripalimab (ORR = 20%; 1/5 evaluable)."

P1/2 data • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

KEYNOTE-C97: ADG116 in Combination With Pembrolizumab in Patients With Advanced/Metastatic Solid Tumors (clinicaltrials.gov) - P1 | N=6 | Completed | Sponsor: Adagene Inc | Phase classification: P1b ➔ P1

Phase classification • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Prostate Cancer • Solid Tumor

ADG116-1003: A Phase 1b/2 Study of ADG116, ADG116 Combined With Anti-PD-1 Antibody or Anti-CD137 Antibody in Solid Tumors Patients (clinicaltrials.gov) - P1 | N=72 | Active, not recruiting | Sponsor: Adagene Inc | Recruiting ➔ Active, not recruiting

Enrollment closed • Oncology • Solid Tumor

Optimal dose selection of ADG126 (a masked anti-CTLA-4 SAFEbody®) with significantly widened therapeutic index compared to ipilimumab in combination with anti-PD-1 antibodies informed by QSP modeling (SITC 2023) - "2 Furthermore, a novel safety model was developed incorporating data for ipilimumab, tremelimumab, pembrolizumab and nivolumab. 3 4 The two models predict optimal dosing regimens, which warrant further clinical investigation to unleash the full therapeutic potential of ADG126 within targeted toxicities. Conclusions The continuously widened TI from ADG116 to ADG126 enables ADG126 to be dosed at 10 mg/kg Q3W and likely higher with anti-PD-1, resulting in significantly higher and sustained tumor target engagement than ipilimumab, potentially translating to greater clinical benefits."

Combination therapy • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Adagene Reports Six Month Financial Results for 2023 and Provides Corporate Update (GlobeNewswire) - "R&D expenses were US$21.3 million for the six months ended June 30, 2023, compared to US$45.1 million for the same period in 2022. The decrease of approximately 53% in R&D expenses reflects a reduction in preclinical spending and winding down of the ADG106 clinical program, offset by investment in the anti-CTLA-4 franchise."

Commercial • Discontinued • Breast Cancer • Follicular Lymphoma • Gastrointestinal Cancer • Head and Neck Cancer • Hematological Malignancies • Hepatocellular Cancer • Liver Cancer • Lung Cancer • Lymphoma • Malignant Pleural Mesothelioma • Mesothelioma • Nasopharyngeal Carcinoma • Non Small Cell Lung Cancer • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor • Triple Negative Breast Cancer

ADG116-1003: A Phase 1b/2 Study of ADG116, ADG116 Combined With Anti-PD-1 Antibody or Anti-CD137 Antibody in Solid Tumors Patients (clinicaltrials.gov) - P1b/2 | N=77 | Recruiting | Sponsor: Adagene Inc | Phase classification: P1b ➔ P1b/2 | N=204 ➔ 77

Enrollment change • Metastases • Phase classification • Oncology • Solid Tumor

KEYNOTE-C97: ADG116 in Combination With Pembrolizumab in Patients With Advanced/Metastatic Solid Tumors (clinicaltrials.gov) - P1b | N=6 | Completed | Sponsor: Adagene Inc | Recruiting ➔ Completed | N=12 ➔ 6 | Trial primary completion date: Dec 2022 ➔ Aug 2022

Combination therapy • Enrollment change • Metastases • Trial completion • Trial primary completion date • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Prostate Cancer • Solid Tumor

Adagene Reports Full Year 2022 Financial Results and Provides Corporate Update (GlobeNewswire) - "UPDATED MILESTONES & OUTLOOK:...(i) Establish registration path and strategy (e.g., recommended phase 2 dose, indication and design) for phase 2/3 pivotal trial of anti-CTLA-4 in combination with anti-PD-1 therapy in targeted tumors; ADG126 phase 2 proof-of-concept data from combination dose expansion cohorts; Advance ADG116 phase 2 combination dose expansion cohorts; (ii) Providing the path to a potential registrational trial for triple combination with Roche’s atezolizumab/bevacizumab, advance ADG126 randomized phase 1b/2 trial in first-line hepatocellular carcinoma (HCC) conducted by Roche; provide update on trial status."

New P2/3 trial • P2 data • Trial status • Gastrointestinal Cancer • Hepatocellular Cancer • Liver Cancer • Oncology • Solid Tumor

Phase 1 study of ADG126, a novel masked anti-CTLA-4 SAFEbody, that combines tumor-localized activation with strong Treg depletion and soft ligand blocking in patients with advanced solid tumors. (ASCO 2022) - P1, P1b | "One ovarian cancer, and 1 uveal melanoma patient who progressed on nivolumab/ipilimumab, showed > 20% durable reductions in target lesions by CT, and increased CD8+ T cells post-dosing. ADG126 demonstrated excellent tolerability and safety for continuous dosing beyond 4 cycles at 10 mpk and for more than 8 cycles at 1 mpk. Compared to ADG116, its non-masked parental Ab, ADG126 exhibited superior PK and early efficacy signals correlated with increased peripheral CD8+ T cells, in general. ADG126 may offer better safety and efficacy profile than ipilimumab, which could help realize the full potential of blocking the CTLA-4 pathway."

Clinical • P1 data • Eye Cancer • Fatigue • Immune Modulation • Inflammation • Melanoma • Oncology • Ovarian Cancer • Pruritus • Solid Tumor • Uveal Melanoma • CD8

A Phase 1b/2, Open-Label, Dose Escalation and Expansion Study of an Anti-CTLA-4 NEOBodyTM ADG116 in Combination with Pembrolizumab (Anti-PD-1 Antibody) in Patients with Advanced/Metastatic Solid Tumors: A Preliminary Update (SITC 2022) - "Conclusions The current safety data supports the regimen of ADG116 (3 mg/kg)/pembrolizumab (200 mg), Q3W for dose expansion, which is a higher dose than that approved for ipilimumab (1 mg/kg) when in combination with nivolumab for several cancer indications. Additional repeat dosing data are being generated to inform the safety, tolerability, and activity of ADG116 in combination with the anti-PD-1 therapy."

Clinical • Combination therapy • P1/2 data • Oncology • Solid Tumor • CD80

A Phase 1b/2 Study of a Novel Anti-CTLA-4 NEObodyTM ADG116 Monotherapy and in Combination with Toripalimab (Tori; Anti-PD-1 Antibody) in Patients with Advanced/Metastatic Solid Tumors (SITC 2022) - "In preclinical studies, ADG116 has been shown to be more potent and better tolerated than ipilimumab. Conclusions ADG116 monotherapy has cleared multiple dose levels including 15 mpk, a dose higher than any reported anti-CTLA-4 class agents in the repeat dose setting. ADG116 (3 mpk)/Tori (240mg) Q3W continuous dosing showed a manageable safety profile and encouraging efficacy including CR, supporting its further clinical evaluation."

Clinical • Combination therapy • Monotherapy • P1/2 data • Head and Neck Cancer • Kaposi Sarcoma • Oncology • Sarcoma • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • CD80

Adagene Announces Clinical Data at SITC 2022 on Anti-CTLA-4 NEObody, ADG116, Showing Differentiated Safety and Anti-tumor Activity in Heavily Pre-treated Patients with Difficult-to-Treat Tumors (GlobeNewswire) - P1 | N=12 | NCT05277402 | Sponsor: Adagene | "Adagene...announced clinical data from phase 1b/2 studies of its anti-CTLA-4 antibody candidate, ADG116, in two poster presentations at the Society for Immunotherapy of Cancer’s (SITC) Annual Meeting taking place in Boston....Data evaluating ADG116 in combination with pembrolizumab in six heavily pre-treated patients primarily with cold tumors further support the differentiated safety profile of ADG116 dosed at 3 mg/kg every three weeks, and its efficacy potential when combined with pembrolizumab at a flat dose of 200 mg. No TRAEs higher than Grade 3 were reported and no DLT was observed. Additionally, significant changes were observed in a tumor-related biomarker in two patients with metastatic microsatellite-stable (MSS) colorectal cancer (CRC), who experienced a 43% and 27% reduction in carcinoembryonic antigen (CEA) levels, respectively."

P1 data • Microsatellite Instability • Oncology • Solid Tumor

Phase I results demonstrate highly differentiated safety and PK profile of ADG126, a masked anti-CTLA-4 SAFEbody in patients with advanced solid tumors (ESMO 2022) - P1 | "Background Ipilimumab (Ipi), the only approved anti-CTLA-4 mAb, is associated with severe AEs in >20% of Pts as monotherapy at 3 mg/kg (mpk), and 1 mpk is used in combination with nivolumab to mitigate safety concerns. ADG126 SAFEbody applies precision masking peptide to the anti-CTLA-4 ADG116 NEObody™ for 6-fold greater safety over ADG116, and has an improved safety and efficacy profile over Ipi...Conclusions ADG126 shows a compelling safety profile with superior PK and early efficacy signals, with only G1 TRAEs as monotherapy given by Q3W for >4 cycles at 10 mpk and >12 cycles at 1 mpk. Combination studies with anti-PD1 therapy are initiated aiming to transform anti-CTLA-4 therapy with improved safety & efficacy."

Clinical • P1 data • Eye Cancer • Melanoma • Oncology • Ovarian Cancer • Solid Tumor • Uveal Melanoma • CD8

Phase 1 dose-finding study of a novel anti-CTLA-4 antibody ADG116 as monotherapy in patients with advanced solid tumors (ESMO-IO 2021) - P1 | "It targets a novel epitope and is more potent but safer than ipilimumab in preclinical studies through two distinct mechanisms: 1) effective T cell activation by softer blocking the interaction between CTLA-4 and its ligands, and 2) stronger ADCC-mediated Treg depletion in tumor microenvironment but not in peripheral tissues...Clinical assessment of ADG116 supports its development as a highly differentiated anti-CTLA-4 therapy for advanced solid tumors as monotherapy and potential partnering agent including a planned combination study with pembrolizumab...Legal entity responsible for the study Adagene Inc. Funding Adagene Inc."

Clinical • IO biomarker • Monotherapy • P1 data • Oncology • Solid Tumor • CD4 • CD8

Adagene Announces Poster Presentations on Anti-CTLA-4 NEObody, ADG116, at Upcoming Society for Immunotherapy of Cancer’s (SITC) Annual Meeting in November (GlobeNewswire) - "Adagene...announced that it will present clinical data from phase 1b/2 studies of its anti-CTLA-4 antibody candidate, ADG116, at the upcoming Society for Immunotherapy of Cancer’s (SITC) Annual Meeting....The posters will summarize the comprehensive safety data for ADG116 with repeat dosing as monotherapy, as well as new data supporting its optimal dose selection in combination with two different anti-PD-1 therapies. Additionally, data will show anti-tumor activity in warm and cold tumors, including details of a partial response with monotherapy and a complete response in combination therapy, which were both observed in tumor types where no anti-CTLA-4 therapy is approved."

P1/2 data • Oncology • Solid Tumor

Adagene Reports Financial Results for the Six Months Ended June 30, 2022 and Provides Corporate Updates (GlobeNewswire) - P1 | N=204 | NCT04501276 | Sponsor: Adagene Inc | "ADG116 (anti-CTLA-4 NEObody™ targeting a unique epitope) - Encouraging efficacy demonstrated as a single agent and in combination with anti-PD-1: Observed one partial response with ADG116 monotherapy in a tumor type where no anti-CTLA-4 therapy is currently approved. Observed one confirmed rapid complete response with repeat dosing for ADG116 in combination with toripalimab in a tumor type where no anti-CTLA-4 therapy is currently approved. Presentation of data from this phase 1b/2 trial will take place at the Society for Immunotherapy of Cancer’s 37th Annual Meeting (SITC 2022) in Boston, November 8-12, 2022."

P1 data • Oncology • Solid Tumor

Adagene Reports Financial Results for the Six Months Ended June 30, 2022 and Provides Corporate Updates (GlobeNewswire) - "UPDATED MILESTONES & OUTLOOK: (i) 2022: ADG116 results of dose escalation in combination with anti-PD-1 therapy to establish the dose(s) and schedule(s) for dose expansion; advance phase 2a dose expansion cohorts in targeted tumors; ADG126 results of dose escalation in combination with anti-PD-1 therapy to establish the dose(s) and schedule(s) for dose expansion; advance phase 2a dose expansion cohorts in targeted tumors; (ii) 2023: ADG116 phase 2a proof-of-concept data from combination dose expansion cohorts; ADG126 phase 2a proof-of-concept data from combination dose expansion cohorts."

P2 data • Trial status • Oncology • Solid Tumor

KEYNOTE-C97: ADG116 in Combination With Pembrolizumab in Patients With Advanced/Metastatic Solid Tumors (clinicaltrials.gov) - P1b | N=12 | Recruiting | Sponsor: Adagene Inc | Not yet recruiting ➔ Recruiting

Combination therapy • Enrollment open • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor

Adagene Reports Full Year 2021 Financial Results and Provides Corporate Update (GlobeNewswire) - "Additional milestones and expected progress during 2022 include: Demonstrate single-agent activity for anti-CTLA-4 programs (ADG116, ADG126) in heavily pretreated patients with “warm” and “cold” tumors; Demonstrate potential best-in-class safety and preliminary efficacy profiles for anti-CTLA-4 programs with anti-PD-1 therapy; Evaluate the profile for novel combinations of wholly owned anti-CD137 (ADG106) with either anti-CTLA-4 or anti-PD-1 therapy."

Clinical • Oncology • Solid Tumor

KEYNOTE-C97: ADG116 in Combination With Pembrolizumab in Patients With Advanced/Metastatic Solid Tumors (clinicaltrials.gov) - P1b | N=12 | Not yet recruiting | Sponsor: Adagene Inc

Combination therapy • New P1 trial • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor

ADG116-1003: A Phase 1b Study of ADG116, ADG116 Combined With Anti-PD-1 Antibody or Anti-CD137 Antibody in Solid Tumors Patients (clinicaltrials.gov) - P1b | N=204 | Recruiting | Sponsor: Adagene Inc | Phase classification: P1 ➔ P1b | N=60 ➔ 204 | Trial completion date: Feb 2023 ➔ Dec 2023 | Trial primary completion date: Sep 2022 ➔ Jul 2023

Enrollment change • Phase classification • Trial completion date • Trial primary completion date • Hepatocellular Cancer • Oncology • Solid Tumor

Adagene Announces First Patient Dosed with Novel, Proprietary Combination of Anti-CD137 Agonist, ADG106, and Anti-CTLA-4 Monoclonal Antibody, ADG116 (GlobeNewswire) - "'Existing cancer therapies that target CD137 and CTLA-4 are associated with safety concerns, creating a significant unmet need and high threshold for agents that are both safe and potent. With ADG106 and ADG116, we now have two promising agents to test the therapeutic potential of these two potent pathways together to safely inhibit tumor growth,' said Anthony W. Tolcher...we finally have the rare and exciting opportunity to be the first to move this combination into clinic and improve patient care.'"

Media quote • Oncology • Solid Tumor