Adagene (NASDAQ:ADAG) highlighted updated details around its lead immuno-oncology program, ADG126, during an Oppenheimer discussion featuring Chief Strategy Officer Mickael Chane-Du. The company is developing ADG126 as a “masked” anti-CTLA-4 antibody intended to improve the safety of CTLA-4 blockade while enabling higher dosing in combination regimens, particularly with Merck’s KEYTRUDA (pembrolizumab).
Focus on late-line MSS colorectal cancer without liver metastases
Chane-Du said Adagene’s initial clinical focus is late-line microsatellite stable colorectal cancer (MSS-CRC) in patients without liver metastases, a setting he described as having low response rates to current standards of care and poor overall survival outcomes. He noted that PD-1 therapies have not shown meaningful activity in MSS-CRC as monotherapy in prior studies and that there is no KEYTRUDA label for this patient population.
ADG126 design and rationale
According to the presentation, ADG126 is built on an anti-CTLA-4 antibody backbone (ADG116) that binds a different epitope than ipilimumab or tremelimumab. Chane-Du said this epitope binding is associated with stronger potency and antibody-dependent cellular cytotoxicity (ADCC), citing “10x higher ADCC compared to ipilimumab.”
ADG126 incorporates Adagene’s SAFEbody masking technology, which Chane-Du described as protease-sensitive and intended to activate preferentially in tumor environments with high CTLA-4 levels and certain proteases (including members of the MMP family and uPA). He emphasized that the company is dosing ADG126 as high as 20 mg/kg in combination with pembrolizumab, which he contrasted with historical CTLA-4 dosing constraints due to toxicity.
Clinical results discussed from ASCO 2025 dataset
Chane-Du reviewed results previously presented at ASCO 2025 from a study of ADG126 plus pembrolizumab in late-line MSS-CRC without liver metastases across four dosing cohorts:
- 10 mg/kg every 6 weeks (Q6W)
- 10 mg/kg every 3 weeks (Q3W)
- “Loading” regimen: 20 mg/kg followed by 10 mg/kg every 3 weeks
- 20 mg/kg every 6 weeks
He said the trial enrolled late-line patients, including about one-third who were fourth-line, and included participants from the U.S. and South Korea, which he said produced consistent outcomes. He also noted that patients generally had not received prior immunotherapy because immune checkpoint inhibitors are not labeled for MSS-CRC.
On safety, Chane-Du stated there were no Grade 4 or Grade 5 events reported in the dataset presented and that discontinuation due to adverse events was under 10%. He said Grade 3 adverse events were observed but described them as manageable and transient based on a longitudinal adverse event analysis.
On efficacy, he said no responses were seen in the 10 mg/kg Q6W cohort, while confirmed responses were observed beginning at 10 mg/kg Q3W. He cited a confirmed response rate of 17% (15% confirmed response rate as described) at 10 mg/kg Q3W and said ASCO 2025 data showed a confirmed response rate of 29% in higher-dose cohorts. He also described trends toward improved response rates and duration of response with higher dosing, adding that Adagene expects to update the dataset “very soon” with additional patients and longer follow-up.
Overall survival observations and upcoming updates
Chane-Du also discussed overall survival (OS), describing it as the key endpoint. For a combined set of lower-dose cohorts (10 mg/kg Q3W plus 10 mg/kg Q6W), he said 41 patients had a median OS of 19 months at ASCO with a median follow-up of close to 18 months. He compared this favorably to historical controls he cited, including fruquintinib trials (FRESCO and FRESCO-2) in the same setting and a bevacizumab plus tremelimumab doublet, which he said showed a median OS of 10 months for patients without liver metastases.
He also referenced a 12-month OS benchmark from FRESCO-2 of 45%–50% and said the 10 mg/kg cohort had a 12-month OS rate of 70%. He said Adagene plans to provide updated OS curves and, for the first time, landmark analyses for the 20 mg/kg cohorts.
Sanofi investment and partnership structure
Chane-Du reiterated that Sanofi made an equity investment in July 2025 of up to $25 million, with an initial $17 million tranche at $2 per share. He said proceeds were allocated to fund Adagene’s ongoing randomized Phase 2 study of ADG126 plus pembrolizumab in late-line MSS-CRC without liver metastases and referenced the FDA’s “Optimus Project” requirements in discussing that randomized effort.
He also said Sanofi agreed to a trial collaboration evaluating ADG126 with Sanofi’s PD-1/IL-15 bispecific in more than 100 solid tumor patients and expanded a discovery collaboration that began in 2022 by exercising an option on a third SAFEbody program. In Q&A, Chane-Du said Adagene retained all rights to ADG126 and that Sanofi does not have a right of first refusal.
Looking ahead, Chane-Du outlined near- and mid-term catalysts, including an updated ADG126 plus KEYTRUDA dataset in the coming weeks, mid-year data from triplet combinations (including ADG126 plus KEYTRUDA plus fruquintinib in late-line CRC without liver metastases), and data tied to Roche’s Morpheus collaboration in first-line hepatocellular carcinoma involving ADG126 plus atezolizumab and bevacizumab, where he said the trial stopped early after completing a safety run-in at the lowest dose (6 mg/kg Q6W). He also said initial results are expected toward year-end from a Phase 2 investigator-sponsored trial in Singapore evaluating ADG126 plus pembrolizumab in neoadjuvant colorectal cancer.
About Adagene (NASDAQ:ADAG)
Adagene Inc, headquartered in Suzhou, China, is a clinical-stage biopharmaceutical company specializing in the discovery and development of antibody-based therapeutics for cancer and immune-related diseases. Founded in 2017, the company leverages its proprietary immunome technology platform to mine human antibody repertoires and engineer novel monospecific and bispecific antibodies. Adagene’s pipeline includes multiple candidates in preclinical and early clinical development, with a focus on targeting tumor microenvironments and modulating immune checkpoints to enhance anti-tumor efficacy.
At the core of Adagene’s research and development efforts is its Bihanc™ antibody platform, which combines combinatorial phage display, structure-based design and artificial intelligence to optimize binding affinity, specificity and developability.
