ADG106 / Adagene - LARVOL DELTA

ADG126, ADG126 in Combination With Anti PD1 Antibody, and ADG126 in Combination With ADG106 in Advanced/Metastatic Solid Tumors (clinicaltrials.gov) - P1/2 | N=58 | Completed | Sponsor: Adagene Inc | Recruiting ➔ Completed | N=91 ➔ 58 | Trial completion date: Dec 2024 ➔ May 2024

Combination therapy • Enrollment change • Metastases • Trial completion • Trial completion date • Oncology • 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 | 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

A phase Ib/II study of an anti-CD137 agonist antibody ADG106 in combination with weekly paclitaxel and dose-dense doxorubicin/cyclophosphamide. (ASCO 2024) - P1/2 | "Research Funding: National Research Foundation, Singapore; National Medical Research Council, Singapore. ADG106 when combined with ddAC exacerbates neutropenia and is not tolerable despite prophylactic pegfilgrastim. The RP2D of ADG106 in combination with P is 200mg and is safe and tolerable; manageable G3 neutropenia was the most common AE. There are no new safety signals thus far in Phase II."

Combination therapy • IO biomarker • P1/2 data • Breast Cancer • Fatigue • Hematological Disorders • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Infectious Disease • Neutropenia • Oncology • Pain • Pneumonia • Renal Disease • Respiratory Diseases • Solid Tumor • HER-2 • PD-L1

A Phase Ib Safety lead-in, Followed by Phase II Trial of ADG106 in Combination With Neoadjuvant Chemotherapy in HER2 Negative Breast Cancer (clinicaltrials.gov) - P1/2 | N=66 | Active, not recruiting | Sponsor: National University Hospital, Singapore | Recruiting ➔ Active, not recruiting | Phase classification: P2 ➔ P1/2

Combination therapy • Enrollment closed • Phase classification • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Oncology • Solid Tumor

Preclinical characterization and phase 1 results of ADG106 in patients with advanced solid tumors and non-Hodgkin's lymphoma. (PubMed, Cell Rep Med) - P1 | "Circulating biomarkers suggest target engagement by ADG106 and immune modulation of circulating T, B, and natural killer cells and cytokines interferon γ and interleukin-6, which may affect the probability of clinical efficacy. ADG106 has a manageable safety profile and preliminary anti-tumor efficacy in patients with advanced cancers (this study was registered at ClinicalTrials.gov: NCT03802955)."

IO biomarker • Journal • Metastases • P1 data • Preclinical • Hematological Disorders • Hematological Malignancies • Immune Modulation • Immunology • Leukopenia • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor • IFNG • IL6 • TNFRSF9

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

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

ComPACT: Pembrolizumab and ADG106 in Advanced Solid Cancers and Triple Negative Breast Cancer (clinicaltrials.gov) - P1b | N=51 | Recruiting | Sponsor: National University Hospital, Singapore | Not yet recruiting ➔ Recruiting

Enrollment open • Breast Cancer • 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

ADG106-1002: Study of ADG106 With Advanced or Metastatic Solid Tumors and/or Non-Hodgkin Lymphoma (clinicaltrials.gov) - P1 | N=62 | Completed | Sponsor: Adagene (Suzhou) Limited | Active, not recruiting ➔ Completed

Metastases • Trial completion • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor • IL10 • IL2 • IL4 • IL6

Study of ADG106 In Combination With PD-1 Antibody In Advanced or Metastatic Solid Tumors and/or Non Hodgkin Lymphoma (clinicaltrials.gov) - P1/2 | N=25 | Terminated | Sponsor: Adagene (Suzhou) Limited | N=60 ➔ 25 | Trial completion date: Feb 2024 ➔ Feb 2023 | Recruiting ➔ Terminated | Trial primary completion date: Jul 2023 ➔ Feb 2023; The safety of ADG106 combined with triprilimab has been fully understood.The overall clinical benefit of enrolled subjects was limited and further development of ADG106 was reconsidered.

Combination therapy • Enrollment change • Metastases • Trial completion date • Trial primary completion date • Trial termination • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor

Assessment of Biomarker Kinetics for ADG106 (anti-CD137 agonist) as monotherapy or combined with toripalimab (ESMO-IO 2021) - P1, P1/2 | "Legal entity responsible for the study Adagene, Inc. Funding Adagene, Inc."

Biomarker • IO biomarker • Monotherapy • Oncology • CD4 • CD8 • IFNG

A phase 1, first-in-human, dose-escalation study of ADG106, a fully human anti-CD137 agonistic antibody, in subjects with advanced or metastatic solid tumors and/or relapsed/refractory non-Hodgkin lymphoma (AACR-NCI-EORTC 2019) - P1; "Tumor shrinkage and decline in SUV scores on PET CT image was observed in one patient with stage IV Follicular Lymphoma (FL) who was refractory to multiple prior therapies including Rituximab. ADG106 demonstrated excellent safety and tolerability profiles at doses up to 1 mg/kg and currently 3 mg/kg is being explored. Preliminary clinical activity was seen in a patient with FL, which warrants further evaluation. Clinical trial information: NCT03707093."

Clinical • P1 data • Colorectal Cancer • Follicular Lymphoma • Gastrointestinal Cancer • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

ADG126, ADG126 in Combination With Anti PD1 Antibody, and ADG126 in Combination With ADG106 in Advanced/Metastatic Solid Tumors (clinicaltrials.gov) - P1/2 | N=91 | Recruiting | Sponsor: Adagene Inc | Phase classification: P1 ➔ P1/2 | N=146 ➔ 91

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

ComPACT: Pembrolizumab and ADG106 in Advanced Solid Cancers and Triple Negative Breast Cancer (clinicaltrials.gov) - P1b | N=51 | Not yet recruiting | Sponsor: National University Hospital, Singapore | Trial completion date: Oct 2026 ➔ Dec 2026 | Initiation date: Oct 2022 ➔ Dec 2022 | Trial primary completion date: Oct 2025 ➔ Dec 2025

Trial completion date • Trial initiation date • Trial primary completion date • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer

Study of CD137 Agonist ADG106 With Advanced or Metastatic Solid Tumors and/or Non-Hodgkin Lymphoma (clinicaltrials.gov) - P1 | N=49 | Completed | Sponsor: Adagene Inc | Active, not recruiting ➔ Completed | Trial primary completion date: Aug 2021 ➔ Jan 2022

Trial completion • Trial primary completion date • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor

ADG106-1002: Study of ADG106 With Advanced or Metastatic Solid Tumors and/or Non-Hodgkin Lymphoma (clinicaltrials.gov) - P1 | N=62 | Active, not recruiting | Sponsor: Adagene (Suzhou) Limited | Trial completion date: Aug 2022 ➔ Dec 2022

Trial completion date • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor • IL10 • IL2 • IL4 • IL6

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

Adagene Reports Financial Results for the Six Months Ended June 30, 2022 and Provides Corporate Updates (GlobeNewswire) - P1/2 | N=60 | NCT04775680 | Sponsor: Adagene (Suzhou) Limited | "Results from the phase 1b/2 trial (ADG106-1008) in China evaluating ADG106 in combination with toripalimab, showed one observed partial response in a nasopharyngeal carcinoma (NPC) patient out of 20 patients enrolled. Currently, four patients remain on therapy. Given prioritization of its two anti-CTLA-4 clinical programs and potential of its next generation anti-CD137 therapy, ADG206, Adagene is winding down the ADG106-1008 trial and does not intend to proceed with the previously planned trial of ADG106 and pembrolizumab."

Trial termination • Head and Neck Cancer • Nasopharyngeal Carcinoma • Oncology • Solid Tumor

ComPACT: Pembrolizumab and ADG106 in Advanced Solid Cancers and Triple Negative Breast Cancer (clinicaltrials.gov) - P1b | N=51 | Not yet recruiting | Sponsor: National University Hospital, Singapore

New P1 trial • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer

ADG106-1002: Study of ADG106 With Advanced or Metastatic Solid Tumors and/or Non-Hodgkin Lymphoma (clinicaltrials.gov) - P1 | N=62 | Active, not recruiting | Sponsor: Adagene (Suzhou) Limited | Trial completion date: Mar 2022 ➔ Aug 2022 | Trial primary completion date: Feb 2022 ➔ Nov 2021

Trial completion date • Trial primary completion date • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor • IL10 • IL2 • IL4 • IL6

A Phase Ib Safety lead-in, Followed by Phase II Trial of ADG106 in Combination With Neoadjuvant Chemotherapy in HER2 Negative Breast Cancer (clinicaltrials.gov) - P2 | N=66 | Recruiting | Sponsor: National University Hospital, Singapore | Not yet recruiting ➔ Recruiting

Combination therapy • Enrollment open • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Oncology • Solid Tumor

ADG126, ADG126 in Combination With Anti PD1 Antibody, and ADG126 in Combination With ADG106 in Advanced/Metastatic Solid Tumors (clinicaltrials.gov) - P1 | N=146 | Recruiting | Sponsor: Adagene Inc | Trial primary completion date: Nov 2022 ➔ Mar 2024

Combination therapy • Trial primary completion date • Hepatocellular Cancer • Oncology • Solid Tumor

ADG126, ADG126 in Combination With Toripalimab, and ADG126 in Combination With ADG106 in Advanced/Metastatic Solid Tumors (clinicaltrials.gov) - P1 | N=146 | Recruiting | Sponsor: Adagene Inc | N=100 ➔ 146 | Trial completion date: Apr 2023 ➔ Dec 2024

Combination therapy • Enrollment change • Trial completion date • Colorectal Cancer • Hepatocellular Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer

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