Adagene Highlights SAFEbody Pipeline, ADG138 Clinical Launch and 2027 Catalysts

Key Points

• Adagene’s SAFEbody platform is designed to mask antibodies in circulation and activate them within tumors, with lead program muzastotug showing encouraging activity across multiple cancer settings, including hepatocellular carcinoma and MSS colorectal cancer.
• The company has launched clinical development of ADG138, a dual-masked HER2-CD3 T-cell engager intended to reduce off-tumor toxicity; patient dosing is expected during the current quarter.
• Key upcoming catalysts include initial ADG138 safety and efficacy data and randomized Phase II muzastotug data in MSS colorectal cancer expected in the first half of 2027, alongside additional survival and combination-treatment updates.

Adagene NASDAQ: ADAG Chairman, CEO and Co-Founder Peter Luo outlined the clinical-stage biotechnology company’s antibody pipeline, its approach to masked therapies and upcoming development milestones during a discussion focused on its T-cell engager, or TCE, portfolio.

Luo said Adagene’s development strategy centers on targeting tumors while limiting effects on healthy tissue through its SAFEbody platform. The platform uses protease-cleavable masking peptides designed to keep an antibody inactive in circulation and activate it in the tumor microenvironment.

The company’s lead clinical program is muzastotug, a masked anti-CTLA-4 antibody designed to deplete regulatory T cells within tumors. Luo said the program has generated clinical data across more than 250 patients in monotherapy, combinations with PD-1 therapies and triple-combination settings.

SAFEbody Platform and Muzastotug Development

Luo said Adagene differentiates its masking technology through what he described as a precision-oriented approach to designing masking peptides for specific antibody binding interfaces and controlling their activation in tumors.

He cited muzastotug as a clinical example of the platform’s potential, saying the company has evaluated doses 10 to 20 times higher than those used for ipilimumab while monitoring response rates, duration of response, overall survival and late-onset toxicities. He also said the program has received FDA Fast Track designations in microsatellite-stable colorectal cancer, or MSS CRC.

In first-line hepatocellular carcinoma, Luo said a trial adding muzastotug to atezolizumab showed an objective response rate that was nearly double, if not triple, that of a control arm receiving a doublet regimen in a Roche-sponsored randomized trial. He said overall survival had not yet been reached after two years of follow-up, while the control arm had reached roughly 18 months. These comments reflected management’s description of the data during the event.

ADG138 Enters Clinical Development

Adagene is also advancing ADG138, a dual-masked HER2-CD3 T-cell engager that applies the SAFEbody technology to both the HER2 tumor-targeting arm and the CD3 T-cell-binding arm.

Luo said HER2 is expressed in normal tissues including the heart and lungs, creating a need to limit engagement outside tumors. He said ADG138’s HER2 mask provides more than 200-fold masking efficiency, while its CD3 arm has a 100-fold mask. The combined design is intended to preserve potency while widening the therapeutic window, according to Luo.

He said preclinical studies in monkeys showed an approximately 300-fold difference between the masked and unmasked forms. In tumor models, the company observed complete responses at 0.1 milligrams per kilogram in HER2-refractory, HER2-low-expression models, Luo said.

Adagene received clearance from China’s Center for Drug Evaluation to begin an investigational new drug study for ADG138. Luo said the company expected to begin dosing patients during the current quarter and year. As a first-in-human TCE study, the trial will use dose-escalation plans intended to assess safety, drug activation, dosing frequency, circulation levels and early efficacy in patients with HER2-refractory disease.

Autoimmune Programs and Partnerships

Beyond oncology, Luo said Adagene sees potential for masked T-cell engagers in autoimmune disease. He said an early CD20-CD3 program with masking on the CD3 arm produced robust B-cell depletion with reduced cytokine release syndrome in preclinical work. The company is also evaluating multi-targeting TCE designs and is open to collaborations for autoimmune candidates.

Luo also discussed Adagene’s partnerships with Third Arc Bio, Sanofi and Exelixis. In September, Adagene amended its Third Arc collaboration to expand it into a more integrated asset-focused partnership in addition to a technology collaboration. Third Arc will lead and fund development of selected programs using Adagene’s NEObody and SAFEbody platforms, Luo said.

Adagene retains no-cost options to develop and commercialize applicable candidates in Greater China, Singapore and South Korea, according to Luo.

With Sanofi, Adagene is developing next-generation immunotherapies, including mono-, bispecific and multispecific antibodies. Luo said Sanofi has also made a strategic investment in Adagene and is sponsoring global studies combining muzastotug with an investigational immunotherapy in more than 100 patients. Adagene retains worldwide commercial rights to muzastotug and wholly owns ADG138, he said.

Under its Exelixis collaboration, Adagene is applying SAFEbody technology to antibody-drug conjugates, including a masked ROR1-directed ADC. Luo said Exelixis presented preclinical data at AACR indicating enhanced pharmacokinetics and tumor-model activity. He added that Adagene recently received a $2 million preclinical milestone payment from Exelixis and completed a third SAFEbody ADC discovery project with the partner.

Upcoming Catalysts

Luo identified several anticipated milestones, including randomized Phase II data for muzastotug in MSS CRC during the first half of 2027 and emerging Phase I safety and early efficacy data for ADG138. Before the MSS CRC readout, he said Adagene also expects to provide updated Phase Ib/II data on overall survival and duration of response from the 20 mg/kg muzastotug cohort, as well as data for muzastotug plus pembrolizumab in neoadjuvant settings.

About Adagene (NASDAQ:ADAG)

Adagene Inc is a biotechnology company focused on discovering and developing novel antibody-based cancer immunotherapies. The company combines computational methods, antibody engineering and translational research to create medicines designed to address limitations associated with conventional immuno-oncology treatments.

Adagene's technology platform includes NEObody, which is intended to identify antibodies with differentiated binding characteristics, and SAFEbody, a masking technology designed to conditionally activate antibodies in the tumor microenvironment.

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