Adagene (ADAG) reports stronger 20 mg/kg muzastotug results and Fast Track status
Rhea-AI Filing Summary
Adagene Inc. reported updated Phase 1b/2 data for its lead CTLA-4 SAFEbody, muzastotug, in advanced microsatellite stable colorectal cancer without liver metastases, given with pembrolizumab. The combined 20 mg/kg cohorts achieved a confirmed overall response rate of 31% (8/26), versus 13% (5/39) at 10 mg/kg, and median progression-free survival of 6.7 months versus 4.8 months. Median overall survival for the 10 mg/kg cohorts was 19.8 months with 48% of patients alive at two years, while one-year survival at 20 mg/kg reached 80.8%. Safety remained manageable across 67 patients, with a 4% discontinuation rate, no dose-limiting toxicities, and no treatment-related Grade 4 or 5 events, despite higher Grade 3 TRAEs at 20 mg/kg. FDA has granted Fast Track designation for the muzastotug plus pembrolizumab combination, an ongoing randomized Phase 2 trial is enrolling with results expected in the first half of 2027, and a potential registrational study is being planned.
Positive
- Dose-dependent efficacy with durable benefit: Muzastotug 20 mg/kg plus pembrolizumab achieved a 31% confirmed overall response rate and 6.7‑month median PFS, with the 10 mg/kg cohorts showing 19.8‑month median overall survival and 48% two‑year survival in late-line MSS colorectal cancer.
- Regulatory and development momentum: The combination has FDA Fast Track designation, a randomized Phase 2 trial is enrolling with results expected in 1H 2027, and a potential registrational study is being prepared based on the emerging dose regimen.
Negative
- None.
Insights
Early data show dose-dependent efficacy and manageable safety for muzastotug in difficult MSS colorectal cancer.
The results highlight stronger activity for 20 mg/kg muzastotug plus pembrolizumab, with a confirmed overall response rate of 31% in 26 patients compared with 13% at 10 mg/kg. Median progression-free survival improved to 6.7 months versus 4.8 months, and the loading-dose regimen showed particularly long median PFS of 15.4 months.
In the 10 mg/kg cohorts, median overall survival reached 19.8 months with a 48% two-year survival rate, suggesting durable benefit in this late-line microsatellite stable colorectal cancer population. At 20 mg/kg, one-year survival was 80.8%, though follow-up is shorter and median overall survival is not yet reached.
Safety data across 67 patients show a low 4% discontinuation rate, no dose-limiting toxicities, and no Grade 4 or 5 treatment-related adverse events. Grade 3 events were higher at 20 mg/kg but described as transient and manageable. With FDA Fast Track designation and a randomized Phase 2 trial underway, these findings move muzastotug closer to a potential registrational path, though confirmation in larger controlled studies remains essential.
Key Figures
Key Terms
overall response rate financial
median progression-free survival financial
Fast Track designation regulatory
SAFEbody technology technical
randomized Phase 2 trial financial
UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
WASHINGTON, D.C. 20549
FORM 6-K
REPORT OF FOREIGN PRIVATE ISSUER PURSUANT TO
RULE 13a-
16 OR 15d-16 UNDER THE SECURITIES EXCHANGE ACT OF 1934
For the Month of April 2026
Commission File Number: 001-39997
Adagene Inc.
4F, Building C14, No. 218
Xinghu Street, Suzhou Industrial Park
Suzhou, Jiangsu Province, 215123
People’s Republic of China
+86-512-8777-3632
(Address of principal executive offices)
Indicate by check mark whether the registrant files or will file annual reports under cover of Form 20-F or Form 40-F.
Form 20-F x Form 40-F ¨
INFORMATION CONTAINED IN THIS REPORT ON FORM 6-K
On April 2, 2026, Adagene Inc. (the "Company") announced results from the latest data cut from its phase 1b/2 study of muzastotug in patients with advanced microsatellite stable colorectal cancer (MSS CRC) with no liver metastases. FDA has designated muzastotug in combination with Merck's (known as MSD outside of the United States and Canada) anti-PD-1 therapy, KEYTRUDA® (pembrolizumab), as a Fast Track product for adult patients with microsatellite stable metastatic colorectal cancer (MSS mCRC) without current or active liver metastases.
Updated Interim Efficacy Results from Phase 1b/2 Trial
Previous results from a data cut on April 22, 2025 were presented at the annual American Society of Clinical Oncology meeting in June 2025. As of the latest data cut on January 24, 2026, a total of 67 MSS CRC patients with no liver metastases, including those with peritoneal involvement, have been treated with muzastotug at a dose of either 10 mg/kg or 20 mg/kg, in combination with pembrolizumab. The 10 mg/kg dose was administered once every three weeks or once every six weeks. The 20 mg/kg dose was administered once as a loading dose, followed by 10 mg/kg every three weeks, or 20 mg/kg every six weeks.
Among 65 efficacy-evaluable patients in the dose expansion phase, those in the combined 10 mg/kg cohorts (N=39) demonstrated an ORR of 13% (5/39), which was comprised of an ORR of 0% (0/10) in the Q6W regimen cohort and an ORR of 17% (5/29) in the every 3 weeks (Q3W) cohort. The higher response rates in the Q3W cohort and robust safety data, to keep patients stable without new lesions, in the Q6W cohort helped inform the decision for the dosing regimens utilized in Arm A of the ongoing randomized phase 2 trial.
The combined 20 mg/kg cohorts (N=26) demonstrated a confirmed ORR of 31% (8/26), including 25% (3/12) in the Q6W cohort and 36% (5/14) in the 20 mg/kg loading dose cohort (20 mg/kg, followed by 10 mg/kg Q3W). The higher response rate in the 20 mg/kg cohorts helped inform the 20 mg/kg induction/ maintenance dosing regimen utilized in Arm B of the ongoing randomized phase 2 trial.
Median progression-free survival was 4.8 months in the 10 mg/kg cohorts and 6.7 months in the 20 mg/kg cohorts. Notably, mPFS was 15.4 months among the 14 patients in the 20 mg/kg loading dose cohort, compared with 4.9 months among the 12 patients in the 20 mg/kg Q6W cohort, further supporting the induction/maintenance approach now being evaluated in the ongoing randomized phase 2 study.
| Muzastotug + Pembrolizumab 200 mg Q3W | 10 mg/kg | 20 mg/kg | ||||||||||
| Subpopulation (N) | Combined (N=39) | Q6W (N=10) | Q3W (N=29) | Combined (N=26) | Q6W (N=12) | 20 mg/kg x1 + 10 mg/kg Q3W (N=14) | ||||||
| 13 | 0(a) | 17 | 31 | 25 | 36 | |||||||
| ORR, % (95% CI) | (4 – 27) | (0 – 31) | (6 – 36) | (14 – 52) | (5 – 57) | (13 – 65) | ||||||
| BoR, N (%) | ||||||||||||
| CR | 0 | 0 | 0 | 1(4) | 1(8) | 0 | ||||||
| PR | 5 (13) | 0 | 5(b) (17) | 7 (27) | 2 (17) | 5 (36) | ||||||
| SD | 24 (62) | 7 (70) | 17 (59) | 14 (54) | 7 (58) | 7 (50) | ||||||
| DCR | ||||||||||||
| (CR+PR+SD), %, (95% CI) | 74 (58 – 87) | 70 (35 – 93) | 76 (56 – 90) | 85 (65 – 96) | 83 (52 – 98) | 86 (57 – 98) | ||||||
| mPFS, months (95% CI) | 4.8 (2.6 – 6.7) | 4.5 (1.4 – 7.1) | 4.8 (2.6 – 6.7) | 6.7 (2.7 – NA) | 4.9 (1.2 – NA) | 15.4 (2.6 – NA) | ||||||
| 6-month PFS, % , (95% CI) | 39.6 (24.3 – 54.6) | 40 (12.3 – 67) | 39.6 (21.9 – 56.8) | 50.4 (29.5 – 68.1) | 45.5 (16.7 – 70.7) | 54.5 (25.4 – 76.5) | ||||||
Abbreviations: BoR (best overall response), CR (complete response), PR (partial response), SD (stable disease), DCR (disease control rate)
Efficacy evaluable set (participants who received ≥1 post-baseline scheduled imaging scan)
| (a) | One patient with target lesion assessed as “PR”, overall assessment as “PD” due to new lesion. |
| (b) | Including one unconfirmed PR (10 mg/kg Q3W) |
mOS for the 10 mg/kg cohorts was 19.8 months with a 23.8-month median follow-up, comparing favorably with current standard of care treatments and historical benchmarks in the 11 – 12 month range1. mOS for the 20 mg/kg cohorts was not yet reached, with a median follow-up of 13.1 months. Patients in the 20 mg/kg cohorts demonstrated a 1-year OS rate of 80.8%, while patients in the 10 mg/kg cohorts demonstrated an OS rate of 70.1% at 12 months and 48% at 24 months.
Updated Interim Safety Results from Phase 1b/2 Trial
As of the January 24, 2026 data cutoff, across 67 patients in all cohorts, there was a low 4% overall discontinuation rate, no dose limiting toxicities, and no treatment-related Grade 4 or 5 adverse events (TRAEs). Grade 3 TRAEs were 15% in the combined 10 mg/kg cohorts (0% Q6W; 20% Q3W) and 38% in the combined 20 mg/kg cohorts (25% Q6W; 50% loading dose cohort), which were generally transient and manageable.
The most common treatment-related adverse events were pruritus, fatigue, hypothyroidism, and diarrhea. Regarding GI-related adverse events, the overall incidence of diarrhea, colitis and immune-mediated enterocolitis was relatively low, and such events were generally transient and manageable. The three patients with Grade 3 colitis had all recovered at the time of data cut-off. Infliximab use was low, with approximately 10% of patients requiring its use for management of GI toxicity.
| Preferred Term | All Grades n (%) | Grade 1 n (%) | Grade 2 n (%) | Grade 3 n (%) | ||||
| Any TRAE | 57 (85.1) | 15 (22.4) | 26 (38.8) | 16 (23.9) | ||||
| Pruritus | 25 (37.3) | 20 (29.9) | 5 (7.5) | 0 | ||||
| Fatigue | 15 (22.4) | 12 (17.9) | 3 (4.5) | 0 | ||||
| Hypothyroidism | 13 (19.4) | 3 (4.5) | 10 (14.9) | 0 | ||||
| Diarrhea | 12 (17.9) | 5 (7.5) | 4 (6) | 3 (4.5) | ||||
| Adrenal insufficiency | 10 (14.9) | 1 (1.5) | 9 (13.4) | 0 | ||||
| Decreased appetite | 8 (11.9) | 6 (9) | 2 (3) | 0 | ||||
| Alanine aminotransferase increased | 7 (10.4) | 2 (3) | 4 (6) | 1 (1.5) | ||||
| Arthralgia | 7 (10.4) | 5 (7.5) | 2 (3) | 0 | ||||
| Nausea | 7 (10.4) | 4 (6) | 3 (4.5) | 0 | ||||
| Colitis | 7 (10.4) | 0 | 4 (6) | 3 (4.5) | ||||
| Immune-mediated enterocolitis | 3 (4.5) | 0 | 2 (3) | 1 (1.5) |
Ongoing Phase 2 Randomized Trial
The randomized phase 2 trial design, incorporated into our existing protocol for the phase 1b/2 Trial (NCT05405595) was established following a meeting with the FDA in 2025 and is evaluating two different dose regimens. The first patient was treated in October 2025, and results are expected in the first half of 2027. We intend to take full advantage of the recent Fast Track designation by the FDA to initiate the a potential registrational study of muzastotug pending further FDA feedback regarding the dose regimen identified from ongoing trials.
| · | Patient Population: The trial will enroll up to 60 late-line patients with MSS CRC without liver metastases, including those with peritoneal metastasis/involvement. Patients are randomized 1:1 into one of two treatment arms with muzastotug in combination with pembrolizumab. |
| · | Dose and Regimen: Both arms utilize an induction/maintenance regimen, without cycle limitations for muzastotug. |
| · | Arm A: 10 mg/kg induction dose of muzastotug plus 200 mg pembrolizumab Q3W for 4 doses followed by one 200 mg dose of pembrolizumab; the maintenance phase will dose 10 mg/kg muzastotug Q6W plus 400 mg of pembrolizumab Q6W. |
| · | Arm B: 20 mg/kg induction dose of muzastotug Q6W plus 400 mg pembrolizumab Q6W for 2 doses; the maintenance phase will dose muzastotug at 15 mg/kg Q6W plus 400 mg pembrolizumab Q6W. |
| · | Endpoints: The primary endpoint will be ORR. Secondary endpoints include duration of response, PFS, and OS. |
The information in the paragraphs above under “Information Contained in this Report on Form 6-K” in this Report on Form 6-K shall be deemed to be incorporated by reference into the registration statements on Form F-3 (File Nos. 333-291196 and 333-287161) and Form S-8 (File No. 333-255250) of the Company, filed with the Securities and Exchange Commission (the “SEC”), and to be a part thereof from the date on which this report is furnished, to the extent not superseded by documents or reports subsequently filed or furnished.
On April 2, 2026, the Company issued the press release attached hereto as Exhibit 99.2. The furnishing of the attached press releases is not an admission as to the materiality of any information therein. The information contained in the press releases is summary information that is intended to be considered in the context of more complete information included in the Company’s filings with the SEC and other public announcements that the Company has made and may make from time to time. The Company undertakes no duty or obligation to update or revise the information contained in this report, although it may do so from time to time as its management believes is appropriate. Any such updating may be made through the filing or furnishing of other reports or documents with the SEC or through other public disclosures.
Forward-Looking Statements
The Company cautions that statements included in this report that are not a description of historical facts are forward-looking statements. Words such as “may,” “could,” “will,” “would,” “should,” “expect,” “plan,” “anticipate,” “believe,” “estimate,” “intend,” “predict,” “seek,” “contemplate,” “look forward,” “potential,” “continue” or “project” or the negative of these terms or other comparable terminology are intended to identify forward-looking statements. These statements include the Company’s plans to advance the development of its product candidates, the timing of achieving any development or regulatory milestones or reporting data or whether such milestones or data will be achieved or generated, including whether any new drug application will be submitted or accepted and the timing thereof, and the potential of such product candidates, including to achieve any benefit, improvement, differentiation, trend or profile or any product approval or be effective. The inclusion of forward-looking statements should not be regarded as a representation by the Company that any of its plans will be achieved. Actual data may differ materially from those set forth in this report due to the risks and uncertainties inherent in the Company’s business and other risks described in the Company’s filings with the Securities and Exchange Commission (“SEC”), including the Company’s Annual Report on Form 20-F filed with the SEC on April 1, 2026, and its other reports. Investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof, and the Company undertakes no obligation to revise or update this report to reflect events or circumstances after the date hereof. Further information regarding these and other risks is included in the Company’s filings with the SEC which are available from the SEC’s website (www.sec.gov). All forward-looking statements are qualified in their entirety by this cautionary statement. This caution is made under the safe harbor provisions of Section 21E of the Private Securities Litigation Reform Act of 1995.
SIGNATURES
Pursuant to the requirements of the Securities Exchange Act of 1934, the Registrant has duly caused this report to be signed on its behalf by the undersigned, thereunto duly authorized.
| Adagene Inc. | ||
| By: | /s/ Peter Luo | |
| Name: | Peter Luo | |
| Title: | Chief Executive Officer | |
| Date: April 2, 2026 | ||
EXHIBIT INDEX
| Exhibit | Description | |
| 99.1 | Press release titled “Adagene Announces Clinical Collaboration with Incyte to Evaluate Muzastotug (ADG126) in Combination with Incyte's TGFßR2xPD-1 Bispecific Antibody (INCA33890) in Patients with Microsatellite Stable Colorectal Cancer (MSS CRC)” | |
| 99.2 | Press release titled “Updated Data from Phase 1b/2 Study of Muzastotug in Combination with KEYTRUDA® (pembrolizumab) in Late-line Patients with Microsatellite Stable Colorectal Cancer Demonstrate Improved Durability of Response” |
Exhibit 99.1
Confidential
Adagene Announces Clinical Collaboration with
Incyte to Evaluate Muzastotug (ADG126) in
Combination with Incyte’s TGFßR2xPD-1 Bispecific Antibody (INCA33890) in Patients
with
Microsatellite Stable Colorectal Cancer (MSS CRC)
Phase 1 study of INCA33890 and muzastotug expected to begin in 2026 in 3L MSS CRC patients with and without liver metastases
Study will be sponsored and conducted by Incyte; Adagene to provide clinical supply of muzastotug
Collaboration provides additional validation of muzastotug as a potential backbone therapy for next-generation immuno-oncology combinations
SAN DIEGO and SUZHOU, China, April 2, 2026 (GLOBE NEWSWIRE) -- Adagene Inc. (“Adagene”) (Nasdaq:ADAG), a company transforming the discovery and development of novel antibody-based therapies, today announced a clinical collaboration with Incyte (Nasdaq:INCY), to evaluate the combination of muzastotug (ADG126) and INCA33890, a TGFβR2 × PD-1 bispecific antibody, in patients with microsatellite stable colorectal cancer (MSS CRC) with or without liver metastases.
Muzastotug in combination with Merck’s (known as MSD outside of the United States and Canada) anti-PD-1 therapy, KEYTRUDA® (pembrolizumab) has demonstrated encouraging overall response rates and durable responses in a Phase 1b/2 trial in 3L MSS CRC patients. As a monotherapy, INCA33890 has demonstrated promising clinical efficacy and safety in immune checkpoint sensitive and insensitive cancers, including MSS CRC with and without liver metastases. Incyte has recently initiated a Phase 3 study (NCT07284849) evaluating bevacizumab and FOLFOX (standard of care chemotherapy) with or without INCA33890 in 700 first-line MSS CRC patients.
“This strategic collaboration marks the second instance in which Adagene’s SAFEbody® technology is being paired with a leading PD-1–based bispecific, further reinforcing muzastotug’s potential as a backbone immunotherapy with a wider therapeutic index for next-generation immuno-oncology combinations.” said Peter Luo, Ph.D., CEO and President of R&D at Adagene. “We look forward to the clinical insights this study may provide to support our belief that muzastotug has the potential to both improve overall response rate and extend survival, meaningfully enhancing the clinical benefit for patients.”
“This collaboration allows us to explore a novel combination approach for patients with microsatellite stable colorectal cancer, a disease that remains resistant to current immunotherapies,” said Pablo J. Cagnoni, M.D., President, Head of Research & Development at Incyte. “By evaluating INCA33890 in combination with muzastotug, we aim to better understand whether complementary mechanisms may help enhance anti-tumor immune responses particularly for patients with liver metastases, who have an especially poor prognosis and limited treatment options.”
1
Muzastotug, a masked anti-CTLA-4 SAFEbody® with FDA Fast Track designation, is currently being evaluated in multiple ongoing studies, including:
| · | A Phase 1b/2 clinical trial in combination with pembrolizumab in MSS CRC patients without liver metastases. |
| · | A randomized Phase 2 study in MSS CRC patients without liver metastases designed to determine the optimal dose to advance into a Phase 3 registration trial. |
| · | A Phase 1b/2 dose escalation and expansion study of muzastotug in combination with Sanofi’s SAR445877 (PD-1 x IL-15 fusion protein) in adults with advanced solid tumors. |
Under terms of the agreement, Incyte will sponsor and conduct the study and Adagene will provide clinical trial supply of muzastotug. The planned dose escalation portion of the study will evaluate safety and tolerability, followed by an efficacy expansion cohort in patients with chemotherapy-refractory MSS CRC patients with and without liver metastases. MSS CRC is well-known to be largely non-responsive to anti-PD-1 / PD-L1 therapy. INCA33890 monotherapy has demonstrated promising initial clinical efficacy and safety in immune checkpoint sensitive/insensitive tumors, including MSS CRC with and without liver metastases.
About Adagene
Adagene Inc. (Nasdaq: ADAG) is a platform-driven, clinical-stage biotechnology company committed to transforming the discovery and development of novel antibody-based cancer immunotherapies. Adagene combines computational biology and artificial intelligence to design novel antibodies that address globally unmet patient needs. The company has forged strategic collaborations with reputable global partners that leverage its SAFEbody precision masking technology in multiple approaches at the vanguard of science.
Powered by its proprietary Dynamic Precision Library (DPL) platform, composed of NEObody™, SAFEbody, and POWERbody™ technologies, Adagene’s highly differentiated pipeline features novel immunotherapy programs. The company’s SAFEbody technology is designed to address safety and tolerability challenges associated with many antibody therapeutics by using precision masking technology to shield the binding domain of the biologic therapy. Through activation in the tumor microenvironment, this allows for tumor-specific targeting of antibodies, while minimizing on-target off-tumor toxicity in healthy tissues.
Adagene’s lead clinical program, muzastotug (ADG126), is a masked, anti-CTLA-4 SAFEbody with FDA Fast Track designation that targets a unique epitope of CTLA-4 in regulatory T cells (Tregs) in the tumor microenvironment. Muzastotug is currently in Phase 1b/2 and Phase 2 clinical studies in combination with anti-PD-1 therapy, particularly focused on metastatic microsatellite-stable (MSS) colorectal cancer (CRC). Validated by ongoing clinical research, the SAFEbody platform can be applied to a wide variety of antibody-based therapeutic modalities, including Fc empowered antibodies, antibody-drug conjugates, and bi/multispecific T-cell engagers.
For more information, please visit: https://investor.adagene.com.
Follow Adagene on WeChat, LinkedIn and X.
2
SAFEbody® is a registered trademark in the United States, China, Australia, Japan, Singapore, and the European Union.
KEYTRUDA® is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.
Adagene Contacts:
Investors:
Raymond Tam
raymond_tam@adagene.com
Corey Davis, Ph.D.
LifeSci Advisors
1-212-915-2577
cdavis@lifesciadvisors.com
Media:
Lindsay Rocco
Elixir Health Public Relations
1-862-596-1304
lrocco@elixirhealthpr.com
3
Exhibit 99.2
Confidential
Updated Data from Phase 1b/2 Study of Muzastotug
in Combination with KEYTRUDA®
(pembrolizumab) in Late-line Patients with Microsatellite Stable Colorectal Cancer Demonstrate
Improved Durability of Response
Dose-Dependent Efficacy Results: As of the latest data cut, muzastotug achieved a 31% (8/26) confirmed overall response rate (ORR) in the combined 20 mg/kg dose cohorts, showing a clear improvement over the 13% ORR (5/39) in the combined 10 mg/kg dose cohorts
Extended Durability: Median duration of response (mDOR) was not yet reached in the 20 mg/kg cohorts, with responses ongoing beyond 9 months; confirmed mDOR of 6.2 months in the 10 mg/kg cohorts
Meaningful Progression-Free Survival (PFS): Median PFS was 6.7 months in the combined 20 mg/kg cohorts, outperforming the 4.8 months observed in the combined 10 mg/kg cohorts
Favorable Overall Survival Results: In the 10 mg/kg cohorts (n=41; median follow-up, 23.8 months), median overall survival was 19.8 months, with 48% of patients alive at two years, showing the long-tail survival typical of CTLA-4 immunotherapy. At 20 mg/kg, one-year survival was 80.8% vs. 70.1% at 10 mg/kg
Expanded Therapeutic Window: Across 67 patients in all cohorts, a low 4% overall discontinuation rate, no dose limiting toxicities, and no Grade 4 or 5 treatment-related adverse events (TRAEs); Grade 3 TRAEs were 15% in the 10 mg/kg cohorts and 38% in the 20 mg/kg cohorts, which were generally transient and manageable
Clear Clinical Path Forward: Randomized Phase 2 trial enrollment ongoing, with results expected in 1H 2027; potential registration trial expected to begin once recommended dose regimen has been established
SAN DIEGO and SUZHOU, China, April 2, 2026 (GLOBE NEWSWIRE) -- Adagene Inc. (“Adagene”) (Nasdaq: ADAG), a company transforming the discovery and development of novel antibody-based therapies, today announced results from the latest data cut from its Phase 1b/2 study of muzastotug in patients with advanced microsatellite stable colorectal cancer (MSS CRC) with no liver metastases. FDA has designated muzastotug in combination with Merck’s (known as MSD outside of the United States and Canada) anti-PD-1 therapy, KEYTRUDA® (pembrolizumab), as a Fast Track product for adult patients with microsatellite stable metastatic colorectal cancer (MSS mCRC) without current or active liver metastases.
"Historically, patients with late-line MSS colorectal cancer have faced limited options and poor outcomes with standard immunotherapies," stated Dr. Marwan Fakih, Professor of Medical Oncology and Therapeutics Research at City of Hope. "The latest data on muzastotug combined with pembrolizumab shows a meaningful clinical benefit for this heavily pretreated group. Beyond the encouraging response durations and overall survival rates—particularly at the 20 mg/kg dose—the safety results are a key differentiator. It potentially allows patients to sustain treatment longer, paving the way for durable disease control while mitigating the severe treatment-related toxicities that have long limited anti-CTLA-4 treatments."
1
"These data offer strong clinical support for our masked antibody platform, demonstrating our potential to expand the therapeutic window for CTLA-4 therapy," said Peter Luo, Ph.D., CEO and President of R&D at Adagene. "The clear dose-dependent response observed at 20 versus 10 mg/kg, along with early survival indicators that track consistently with the immunotherapy-like long tail—highlighted by a 48% survival rate at two years in our mature 10 mg/kg cohorts —gives us high confidence in this program's potentially differentiated profile. Supported by our FDA Fast Track designation, we remain focused on executing our randomized Phase 2 trial and collaborating with regulatory authorities to finalize an optimal dose and registration path."
Updated Interim Efficacy Results from Phase 1b/2 Trial
Previous results from a data cut on April 22, 2025 were presented at ASCO in June 2025. As of the latest data cut on January 24, 2026, a total of 67 MSS CRC patients with no liver metastases, including those with peritoneal involvement, have been treated with muzastotug at a dose of either 10 mg/kg or 20 mg/kg, in combination with pembrolizumab. The 10 mg/kg dose was administered once every three weeks or once every six weeks. The 20 mg/kg dose was administered once as a loading dose, followed by 10 mg/kg every three weeks, or 20 mg/kg every six weeks.
Among 65 efficacy-evaluable patients in the dose expansion phase, those in the combined 10 mg/kg cohorts (N=39) demonstrated an ORR of 13% (5/39), which was comprised of an ORR of 0% (0/10) in the Q6W regimen cohort and an ORR of 17% (5/29) in the Q3W cohort. The higher response rates in the Q3W cohort and robust safety, to keep patients stable without new lesions, in the Q6W cohort helped inform the decision for the dosing regimens utilized in Arm A of the ongoing randomized Phase 2 trial.
The combined 20 mg/kg cohorts (N=26) demonstrated a confirmed ORR of 31% (8/26), including 25% (3/12) in the Q6W cohort and 36% (5/14) in the 20 mg/kg loading dose cohort (20 mg/kg, followed by 10 mg/kg Q3W). The higher response rate in the 20 mg/kg cohorts helped inform the 20 mg/kg induction/maintenance dosing regimen utilized in Arm B of the ongoing randomized Phase 2 trial.
Median progression-free survival was 4.8 months in the 10 mg/kg cohorts and 6.7 months in the 20 mg/kg cohorts. Notably, median PFS was 15.4 months among the 14 patients in the 20 mg/kg loading dose cohort, compared with 4.9 months among the 12 patients in the 20 mg/kg Q6W cohort, further supporting the induction/maintenance approach now being evaluated in the ongoing randomized Phase 2 study.
| Muzastotug + Pembrolizumab 200 mg Q3W |
10 mg/kg | 20 mg/kg | ||||
| Subpopulation (N) | Combined (N=39) |
Q6W (N=10) |
Q3W (N=29) |
Combined (N=26) |
Q6W (N=12) |
20 mg/kg x1 + 10 mg/kg Q3W (N=14) |
| ORR, % (95% CI) | 13 (4-27) |
0a (0-31) |
17 (6-36) |
31 (14-52) |
25 (5-57) |
36 (13-65) |
| BoR, N (%) | ||||||
| CR | 0 | 0 | 0 | 1 (4) | 1 (8) | 0 |
| PR | 5 (13) | 0 | 5b (17) | 7 (27) | 2 (17) | 5 (36) |
| SD | 24 (62) | 7 (70) | 17 (59) | 14 (54) | 7 (58) | 7 (50) |
| DCR (CR+PR+SD), %, (95% CI) | 74 (58-87) |
70 (35-93) |
76 (56-90) |
85 (65-96) |
83 (52-98) |
86 (57-98) |
| Median PFS, months (95%CI) | 4.8 (2.6-6.7) |
4.5 (1.4-7.1) |
4.8 (2.6-6.7) |
6.7 (2.7-NA) |
4.9 (1.2-NA) |
15.4 (2.6-NA) |
| 6-month PFS, %, (95% CI) | 39.6 (24.3-54.6) |
40 (12.3-67) |
39.6 (21.9-56.8) |
50.4 (29.5-68.1) |
45.5 (16.7-70.7) |
54.5 (25.4-76.5) |
Efficacy evaluable set (participants who received ≥1 post-baseline scheduled imaging scan)
a. One patient with target lesion assessed as “PR”, overall assessment as “PD” due to new lesion.
b. Including one unconfirmed PR (10 mg/kg Q3W)
2
Median overall survival (OS) for the 10 mg/kg cohorts was 19.8 months with a 23.8-month median follow-up. Median OS for the 20 mg/kg cohorts was not yet reached, with a median follow-up of 13.1 months. Patients in the 20 mg/kg cohorts demonstrated a 1-year OS rate of 80.8%, while patients in the 10 mg/kg cohorts demonstrated an OS rate of 70.1% at 12 months and 48% at 24 months.
Updated Interim Safety Results from Phase 1b/2 Trial
As of the January 24, 2026 data cutoff, across 67 patients in all cohorts, there was a low 4% overall discontinuation rate, no dose limiting toxicities, and no treatment-related Grade 4 or 5 adverse events (TRAEs). Grade 3 TRAEs were 15% in the combined 10 mg/kg cohorts (0% Q6W; 20% Q3W) and 38% in the combined 20 mg/kg cohorts (25% Q6W; 50% loading dose cohort), which were generally transient and manageable.
The most common treatment-related adverse events were pruritus, fatigue, hypothyroidism, and diarrhea. Regarding GI-related adverse events, the overall incidence of diarrhea, colitis and immune-mediated enterocolitis was relatively low, and such events were generally transient and manageable. The three patients with Grade 3 colitis had all recovered at the time of data cut-off. Infliximab use was low, with approximately 10% of patients requiring its use for management of GI toxicity.
| Preferred Term | All Grade n (%) |
Grade 1 n (%) |
Grade 2 n (%) |
Grade 3 n (%) |
| Any TRAE | 57 (85.1) | 15 (22.4) | 26 (38.8) | 16 (23.9) |
| Pruritus | 25 (37.3) | 20 (29.9) | 5 (7.5) | 0 |
| Fatigue | 15 (22.4) | 12 (17.9) | 3 (4.5) | 0 |
| Hypothyroidism | 13 (19.4) | 3 (4.5) | 10 (14.9) | 0 |
| Diarrhea | 12 (17.9) | 5 (7.5) | 4 (6) | 3 (4.5) |
| Adrenal insufficiency | 10 (14.9) | 1 (1.5) | 9 (13.4) | 0 |
| Decreased appetite | 8 (11.9) | 6 (9) | 2 (3) | 0 |
| Alanine aminotransferase increased | 7 (10.4) | 2 (3) | 4 (6) | 1 (1.5) |
| Arthralgia | 7 (10.4) | 5 (7.5) | 2 (3) | 0 |
| Nausea | 7 (10.4) | 4 (6) | 3 (4.5) | 0 |
| Colitis | 7 (10.4) | 0 | 4 (6) | 3 (4.5) |
| Immune-mediated enterocolitis | 3 (4.5) | 0 | 2 (3) | 1 (1.5) |
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Ongoing Phase 2 Randomized Trial
The randomized Phase 2 trial design, incorporated into the Company’s existing protocol for the Phase 1b/2 Trial (NCT05405595) was established following a meeting with the US Food and Drug Administration (FDA) in 2025 and is evaluating two different dose regimens. The first patient was treated in October 2025, and results are expected in 1H 2027. The Company intends to take full advantage of the recent Fast Track designation by the FDA to initiate a potential registration study of muzastotug pending further FDA feedback regarding the dose regimen identified from ongoing trials.
| · | Patient Population: The trial will enroll up to 60 late-line patients with MSS CRC without liver metastases, including those with peritoneal metastasis/involvement. Patients are randomized 1:1 into one of two treatment arms with muzastotug in combination with pembrolizumab. |
| · | Dose and Regimen: Both arms utilize an induction/maintenance regimen, without cycle limitations for muzastotug. |
| · | Arm A: 10 mg/kg induction dose of muzastotug plus 200 mg pembrolizumab every 3 weeks (Q3W) for 4 doses followed by one 200 mg dose of pembrolizumab; the maintenance phase will dose 10 mg/kg muzastotug every 6 weeks (Q6W) plus 400 mg of pembrolizumab Q6W. |
| · | Arm B: 20 mg/kg induction dose of muzastotug Q6W plus 400 mg pembrolizumab Q6W for 2 doses; the maintenance phase will dose muzastotug at 15 mg/kg Q6W plus 400 mg pembrolizumab Q6W. |
| · | Endpoints: The primary endpoint will be overall response rate (ORR). Secondary endpoints include duration of response (DOR), progression-free survival (PFS), and overall survival (OS). |
| 1. | Qin S, Xu RH, Shen L, Et Al. Subgroup Analysis By Liver Metastasis In The FRESCO Trial Comparing Fruquintinib Versus Placebo Plus Best Supportive Care In Chinese Patients With Metastatic Colorectal Cancer. Onco Targets Ther. 2021;14:4439-; Garcia-Carbonero R, Dasari NA, Eng C, et al. 520P Efficacy and safety of fruquintinib in patients with refractory metastatic colorectal cancer with and without liver metastasis: A subgroup analysis of the phase III FRESCO-2 trial. Ann Onc 2024;35:S439 |
About Adagene
Adagene Inc. (Nasdaq: ADAG) is a platform-driven, clinical-stage biotechnology company committed to transforming the discovery and development of novel antibody-based cancer immunotherapies. Adagene combines computational biology and artificial intelligence to design novel antibodies that address globally unmet patient needs. The company has forged strategic collaborations with reputable global partners that leverage its SAFEbody precision masking technology in multiple approaches at the vanguard of science.
Powered by its proprietary Dynamic Precision Library (DPL) platform, composed of NEObody™, SAFEbody, and POWERbody™ technologies, Adagene’s highly differentiated pipeline features novel immunotherapy programs. The company’s SAFEbody technology is designed to address safety and tolerability challenges associated with many antibody therapeutics by using precision masking technology to shield the binding domain of the biologic therapy. Through activation in the tumor microenvironment, this allows for tumor-specific targeting of antibodies, while minimizing on-target off-tumor toxicity in healthy tissues.
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Adagene’s lead clinical program, muzastotug (ADG126), is a masked, anti-CTLA-4 SAFEbody with FDA Fast Track designation that targets a unique epitope of CTLA-4 in regulatory T cells (Tregs) in the tumor microenvironment. Muzastotug is currently in Phase 1b/2 and Phase 2 clinical studies in combination with anti-PD-1 therapy, particularly focused on metastatic microsatellite-stable (MSS) colorectal cancer (CRC). Supported by ongoing clinical research, Adagene believes the SAFEbody platform can be applied to a wide variety of antibody-based therapeutic modalities, including Fc empowered antibodies, antibody-drug conjugates, and bi/multispecific T-cell engagers.
For more information, please visit: https://investor.adagene.com.
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SAFEbody® is a registered trademark in the United States, China, Australia, Japan, Singapore, and the European Union.
KEYTRUDA® is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.
Investor Contacts:
Raymond Tam
raymond_tam@adagene.com
Corey Davis, Ph.D.
LifeSci Advisors
212-915-2577
cdavis@lifesciadvisors.com
Media Contact:
Lindsay Rocco
Elixir Health PR
862-596-1304
lrocco@elixirhealthpr.com
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