Adagene Reports Year-End 2023 Financial Results and Corporate Updates

March 29, 2024 by No Comments

– Data for masked anti-CTLA-4 SAFEbody® ADG126 (muzastotug) highlighted a best-in-class therapeutic index and demonstrated clinical benefits in metastatic microsatellite-stable (MSS) colorectal cancer (CRC) with higher, more frequent and repeat dosing of anti-CTLA-4 therapy in combination with anti-PD-1 – – The ongoing combination phase 2 dose expansion in MSS CRC increased to over 50 patients, including initiation of a new, unprecedented 20 mg/kg loading dose regimen, with data anticipated during 2024 – – Validation of SAFEbody masking technology by Exelixis and Sanofi showcased the versatility of the platform across modalities including antibody-drug conjugates, bi-specific and monoclonal antibodies – – A cash balance of approximately US$110 million funded streamlined operations into 2026 – SAN DIEGO and SUZHOU, China, March 29, 2024 — Adagene Inc. (“Adagene”) (Nasdaq: ADAG), a platform-driven, clinical-stage biotechnology company transforming the discovery and development of novel antibody-based therapies, today reported financial results for the full year 2023 and provided corporate updates. “The SAFEbody precision masking technology platform remains at the core of our value proposition given its ability to enhance next generation antibody-based therapies that span modalities, including bispecific T-cell engagers and antibody-drug conjugates, both areas where a wider therapeutic index is needed to fully address solid tumors,” said Peter Luo, Ph.D., Chairman, CEO and President of R&D at Adagene. He continued, “Turning to our clinical pipeline, we remain steadfast in our belief that anti-CTLA-4 therapy can be reimagined as a cornerstone of cancer care by enabling higher, more frequent and repeated doses in combination with anti-PD-1 and other therapies. With our SAFEbody platform, we have a 30-fold improved therapeutic index for ADG126 and a mechanism enabling CTLA-4 mediated intratumoral Treg depletion. We are taking anti-CTLA-4 therapy to a new level unleashing this proven immunotherapy where safety has limited its therapeutic potential.” “In particular, our new loading dose regimen in late-stage MSS CRC patients enables our masked anti-CTLA-4 therapy to reach a high initial concentration, close to the steady state of activated species within the tumor tissue to immediately engage the CTLA-4 pathway and stop the tumor from aggressive growth. This loading dose strategy, together with repeated maintenance doses at 10 mg/kg showing limited treatment-related grade 3 and no higher toxicities with minimal late-onset toxicities for ADG126, is expected to engage the CTLA-4 target consistently, thereby maintaining and sustaining clinical benefit, via both the initial response rate and prolonged survival benefit. We look forward to reporting more clinical results for the ADG126 combination dose expansion in MSS CRC later this year.” PIPELINE HIGHLIGHTS Phase 1b/2 data for ADG126, a masked anti-CTLA-4 SAFEbody targeting a unique epitope of CTLA-4 on regulatory T cells (Tregs) in tumor tissue as driven by the fundamental biology of CTLA-4, showed a potential best-in-class profile in combination with Merck’s anti-PD-1 therapy, KEYTRUDA® (pembrolizumab)*, in MSS CRC, PD-1 experienced and PD-L1 low tumors: Results presented at the 2024 American Society of Clinical Oncology (ASCO) Gastrointestinal (GI) Symposium from dose escalation and dose expansion cohorts of ADG126 in combination with pembrolizumab (200 mg/Q3W) demonstrated a differentiated safety profile for ADG126 at doses from 6 mg/kg to 10 mg/kg in heavily pre-treated advanced/metastatic patients (N=46): Limited dose-dependent toxicities were observed.Grade 3 TRAEs occurred in 5/46 patients (10.8%), with no Grade 4 or 5 TRAEs and a discontinuation rate of 6.5% (3/46). In dose escalation across tumor types, two partial confirmed responses (PRs) were observed among the three patients treated with ADG126 10 mg/kg Q3W, which triggered expansion cohorts at this dosing regimen. One of the patients had PD-1 refractory cervical cancer and the other had endometrial cancer. Both confirmed PRs are sustained after more than one year with repeat dosing while maintaining robust safety profiles.In dose expansion of patients with MSS CRC, 12 evaluable patients without liver metastases were treated at the active, potent dose of 10 mg/kg Q3W: Two confirmed PRs were observed in nine of these patients without peritoneal and liver metastases, resulting in an overall response rate of 22% in this subset.An additional seven of these nine patients experienced stable disease (SD) for an overall disease control rate of 100% (2 PRs and 7 SD).Observation of these clinical activities triggered further expansion into the second stage of the Simon’s 2-stage design for this dose level. In a preliminary progression-free survival (PFS) analysis of those MSS CRC patients free of liver and peritoneal metastasis, a median PFS of seven months was observed in those treated with ADG126 10 mg/kg at two dosing frequencies pooled together [every three weeks (n=9) and every six weeks (n=6)]. The durable clinical activity of ADG126 in combination with pembrolizumab will continue to be evaluated as a larger cohort of subjects becomes evaluable at the 10 mg/kg Q3W dose level.Following the ASCO GI Symposium, Adagene announced progress and expansion of the ADG126 clinical program, which increases the ongoing phase 2 dose expansion in MSS CRC to over 50 patients. Updates included: Enrollment of 12 additional patients in the second stage of the Simon’s 2-stage design was completed in the fourth quarter of 2023 for the ongoing phase 2 dose expansion cohort evaluating ADG126 10 mg/kg Q3W in combination with pembrolizumab in MSS CRC. These Part 2 results will supplement data from Part 1 of the dose expansion in MSS CRC as recently presented at the 2024 ASCO GI Symposium.Given the ADG126 safety profile, evaluation of the 20 mg/kg loading dose regimen has been initiated in combination with pembrolizumab in patients with advanced/metastatic cancer. Pending outcome of the ongoing safety evaluation, the company plans to evaluate the efficacy profile of the loading dose regimen in expansion cohorts, followed by maintenance with ADG126 10 mg/kg Q3W in combination with pembrolizumab at sites in the US and Asia Pacific.Clearance received from China’s Center for Drug Evaluation to initiate clinical evaluation of ADG126 in combination with pembrolizumab. This enables the company to broaden its dose expansion cohorts for MSS CRC at selected dosing regimens, and potentially in other tumor types, in its clinical trial collaboration and supply agreement with Merck. Additionally, the company recently initiated dosing of a small number of patients with advanced/metastatic cancers at 30 mg/kg ADG126 monotherapy Q3W in China to define the potential maximum tolerated dose of ADG126 monotherapy. Phase 1b/2 data for ADG116, an unmasked anti-CTLA-4 NEObodyTM targeting a unique epitope, 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). An initial PR was also observed in a patient with MSS CRC dosed with repeat cycles of ADG116 3 mg/kg every six weeks plus toripalimab, further demonstrating the potential clinical benefit associated with targeting a unique epitope of CTLA-4 and the essential effects of Treg depletion.ADG116 is clinically active and ready to advance into further clinical development as resources allow. Phase 1 evaluation is ongoing for ADG206, a m