Adagene Announces FDA Fast Track Designation for Muzastotug (ADG126)

Rhea-AI Summary

Adagene (Nasdaq: ADAG) announced that the U.S. FDA granted Fast Track Designation to muzastotug (ADG126) in combination with pembrolizumab for adult patients with MSS metastatic colorectal cancer without active liver metastases on Dec 16, 2025. The designation cites emerging clinical evidence of encouraging efficacy, deep durable responses, and a favorable safety profile in heavily pretreated patients. Fast Track may enable more frequent FDA interactions and rolling review. Adagene is conducting a randomized Phase 2 (10 mg/kg vs 20 mg/kg; up to 30 patients per arm; primary endpoint ORR) and plans a Phase 3 with OS as primary endpoint and a registration trial planned to begin in 2027.

Positive

• Fast Track granted by FDA for muzastotug + pembrolizumab
• Phase 2 dose arms: 10 mg/kg and 20 mg/kg
• Phase 2 enrollment: up to 30 patients per arm
• Phase 3 primary endpoint confirmed as overall survival (OS)
• Registration trial planned to begin in 2027

Negative

• Phase 2 sample size limited to ~30 patients per arm
• Fast Track does not guarantee approval or definitive efficacy

News Market Reaction

+13.77%

3 alerts

+13.77% News Effect

-12.2% Trough Tracked

+$11M Valuation Impact

$90M Market Cap

0.8x Rel. Volume

On the day this news was published, ADAG gained 13.77%, reflecting a significant positive market reaction. Argus tracked a trough of -12.2% from its starting point during tracking. Our momentum scanner triggered 3 alerts that day, indicating moderate trading interest and price volatility. This price movement added approximately $11M to the company's valuation, bringing the market cap to $90M at that time.

Data tracked by StockTitan Argus on the day of publication.

Key Figures

Phase 2 dose levels: 10 mg/kg and 20 mg/kg Phase 2 enrollment: Up to 30 patients per arm Registration trial timing: Planned 2027 start +5 more

8 metrics

Phase 2 dose levels 10 mg/kg and 20 mg/kg Muzastotug plus pembrolizumab randomized Phase 2 dose optimization

Phase 2 enrollment Up to 30 patients per arm Randomized Phase 2 muzastotug study design

Registration trial timing Planned 2027 start Muzastotug registration trial preparation

Ordinary shares registered 10,625,000 shares Form F-3 resale registration

ADSs registered 8,500,000 ADSs Form F-3 resale registration

Preferred shares convertible 1,062,500 shares Series A Non-Voting Redeemable Convertible Preferred

ADS ratio 1 ADS = 1.25 ordinary shares Nasdaq-listed ADAG ADS structure

Pre-news share price $1.67 Close before Fast Track announcement

Market Reality Check

Price: $2.75 Vol: Volume 48,191 is well bel...

low vol

$2.75 Last Close

Volume Volume 48,191 is well below 20-day average of 234,957 (relative volume 0.21), suggesting limited pre-news positioning. low

Technical Shares at $1.67 are trading below the $1.87 200-day MA, indicating a pre-news downtrend.

Peers on Argus

ADAG was down 4.57% with mixed peer action: CRBP, TCRX, PYXS, ZNTL down, while A...

ADAG was down 4.57% with mixed peer action: CRBP, TCRX, PYXS, ZNTL down, while ARMP gained 6.57%. Lack of consistent direction across peers points to stock-specific dynamics.

Historical Context

5 past events · Latest: Nov 13 (Positive)

Pattern 5 events

Date	Event	Sentiment	Move	Catalyst
Nov 13	Licensing agreement	Positive	+1.7%	Third Arc Bio licensing two masked CD3 T cell engagers using SAFEbody.
Oct 31	Phase 2 dosing start	Positive	-7.3%	First patient dosed in randomized Phase 2 dose-optimization cohort for muzastotug.
Sep 16	Collaboration expansion	Positive	+0.9%	Expanded SAFEbody collaboration with Exelixis to develop third masked ADC.
Sep 05	Clinical data preview	Positive	+2.8%	CSCO presentations highlighting ADG126 efficacy and disease control in MSS CRC.
Sep 03	Leadership appointment	Positive	+2.8%	Appointment of immuno-oncology expert Axel Hoos as executive advisor.

Pattern Detected

Recent positive strategic and clinical updates have more often been met with modest positive moves, though the Oct 31 Phase 2 dosing news drew a negative reaction.

Recent Company History

Over the past six months, Adagene has advanced its SAFEbody® platform and muzastotug program through collaborations and clinical milestones. Key events include licensing masked CD3 engagers with Third Arc Bio on Nov 13, 2025, multiple partnership and data updates with Exelixis and CSCO presentations, and clinical progress in Phase 1b/2 and Phase 2 for MSS colorectal cancer. Most of these developments saw small positive price reactions, while the Oct 31, 2025 Phase 2 dosing announcement drew a negative move, showing occasionally inconsistent trading around clinical news.

Regulatory & Risk Context

Active S-3 Shelf

Shelf Active

Active S-3 Shelf Registration 2025-10-31

An effective Form F-3 resale registration dated Oct 31, 2025 covers up to 10,625,000 ordinary shares or 8,500,000 ADSs issuable upon conversion of 1,062,500 preferred shares. Sales would be by a selling shareholder, with Adagene receiving no proceeds, highlighting secondary supply potential without direct capital raise for the company.

Market Pulse Summary

The stock surged +13.8% in the session following this news. A strong positive reaction aligns with t...

Analysis

The stock surged +13.8% in the session following this news. A strong positive reaction aligns with the material nature of FDA Fast Track Designation and the clear Phase 2 and Phase 3 roadmap for muzastotug in MSS colorectal cancer. Past clinical updates have moved the stock by an average of 5.51%, suggesting that sizeable swings around regulatory milestones have precedent. However, existing F-3 resale capacity and historically mixed reactions to trial news could introduce volatility as traders reassess risk and timelines.

Key Terms

fast track, ctla-4, pd-1, pembrolizumab, +4 more

8 terms

fast track regulatory

"has designated muzastotug ... as a Fast Track product for adult patients"

A fast track designation is a regulatory label that speeds up the review and communication between a drug developer and regulators for treatments addressing serious illnesses or unmet medical needs. For investors, it matters because it can shorten development time and reduce regulatory delays—like getting a VIP lane at the airport—raising the chance of earlier market access and potential revenue, though it does not guarantee approval.

ctla-4 medical

"SAFEbody®-enabled anti-CTLA-4 therapy to address unmet need"

CTLA-4 is a protein on certain immune cells that acts like a brake, helping to slow or stop immune responses. Drugs that block CTLA-4 release that brake and can boost the immune system’s ability to attack cancer, but they can also increase the risk of immune side effects. For investors, CTLA-4 is important because it’s a proven drug target with major commercial and regulatory implications for cancer therapies and related safety profiles.

pd-1 medical

"Merck’s ... anti-PD-1 therapy, KEYTRUDA® (pembrolizumab)"

PD-1 is a protein found on certain immune cells that acts like a brake, signaling the immune system to slow down and avoid damaging healthy tissue. Drugs that block PD-1 release that brake so immune cells can better attack cancer cells; because such therapies can produce large clinical benefits, regulatory approvals, trial outcomes, pricing and market uptake for PD-1 drugs can materially affect a drugmaker’s prospects and investor returns.

pembrolizumab medical

"KEYTRUDA® (pembrolizumab), as a Fast Track product"

A cancer immunotherapy drug that helps the body’s immune system recognize and attack tumor cells by blocking a molecular “brake” that tumors use to hide. Investors watch it because regulatory approvals, clinical trial results, dosing rules, and competition directly affect potential sales, profit forecasts, and the valuation of companies that sell or license the drug—think of trial outcomes as checkpoint signs that can open or close a revenue road.

tumor microenvironment medical

"activate antibody binding within the tumor microenvironment, thereby reducing"

The tumor microenvironment is the immediate area surrounding a cancer cell, made up of nearby cells, blood vessels, and support structures that influence how the cancer grows and spreads. It functions like a bustling neighborhood that can either help or hinder the tumor’s development. For investors, understanding changes in this environment can signal the effectiveness of treatments and potential shifts in a cancer-related market.

overall response rate medical

"primary endpoint of the Phase 2 trial will be overall response rate (ORR)"

Overall response rate is the percentage of patients in a clinical study whose measurable disease shrinks or disappears after receiving a treatment. Investors watch it like a product’s “hit rate” because higher response rates can signal a drug’s effectiveness, boost chances of regulatory approval and market demand, and affect a company’s future revenue prospects, similar to how a higher batting average suggests a more reliable player.

progression-free survival medical

"Secondary endpoints include duration of response (DOR), progression-free survival (PFS)"

Progression-free survival is the length of time during and after a treatment that a patient's disease does not get worse, measured from the start of treatment until the disease shows measurable signs of progression or the patient dies. Investors care because longer progression-free survival in clinical trials often signals that a drug is effective, improving chances of regulatory approval, market adoption, and revenue potential—think of it as a stopwatch showing how long a therapy can keep the illness at bay.

overall survival medical

"Phase 3 Endpoints: The primary endpoint of the Phase 3 trial will be OS"

Overall survival is the average or median length of time patients remain alive after starting a treatment or entering a clinical study, measured regardless of cause of death. Investors care because it is a clear, hard measure of a therapy’s real-world benefit — like timing how long a new battery actually runs — and strong improvements in overall survival can drive regulatory approval, market adoption and revenue potential.

AI-generated analysis. Not financial advice.

Designation underscores the potential of SAFEbody®-enabled anti-CTLA-4 therapy to address unmet need in MSS colorectal cancer

SAN DIEGO and SUZHOU, China, Dec. 16, 2025 (GLOBE NEWSWIRE) -- Adagene Inc. (“Adagene”) (Nasdaq: ADAG), a company transforming the discovery and development of novel antibody-based therapies, today announced that the U.S. Food and Drug Administration (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. Muzastotug is a next-generation masked anti-CTLA-4 SAFEbody® engineered to overcome CTLA-4–mediated Treg resistance in tumors with enhanced safety and efficacy, delivering a therapeutic index beyond the reach of existing CTLA-4 therapies.

The Fast Track Designation is supported by emerging clinical evidence demonstrating encouraging efficacy, deep and durable responses, and a favorable safety profile of muzastotug across a heavily pretreated patient population. Fast Track is designed to facilitate drug development and expedite the review of therapies intended to treat serious conditions with unmet medical need.

“Receiving Fast Track Designation marks an important milestone for Adagene and further validates the promise of our SAFEbody® technology to unlock CTLA-4 biology in a fundamentally safer and more effective way,” said Peter Luo, Ph.D., Chief Executive Officer and President of R&D at Adagene. “We are deeply encouraged by the responses we are seeing with muzastotug in combination with pembrolizumab and believe this therapy has the potential to reshape the treatment paradigm by offering patients an opportunity for extended survival with an improved quality of life. We look forward to sharing updated topline Phase 1b/2 clinical data over the next few months as we continue advancing this program with urgency and purpose.”

Muzastotug uses Adagene’s proprietary masking technology to preferentially activate antibody binding within the tumor microenvironment, thereby reducing systemic toxicity while maintaining antitumor potency. Fast Track Designation enables more frequent FDA interactions and may allow for rolling review of future marketing applications as Adagene continues the ongoing randomized Phase 2 and prepares for the registration trial, planned to begin in 2027.

Phase 2 Randomized Trial
Both the randomized Phase 2 and Phase 3 trial designs and endpoints were confirmed following a meeting with the US Food and Drug Administration (FDA):

• Patient Population: Future trials will enroll late-line patients with MSS CRC without liver metastases, including those with peritoneal metastasis/involvement.
• Dose and Regimen: Phase 2 dose optimization cohort will randomize patients to either 10 mg/kg or 20 mg/kg of muzastotug in combination with pembrolizumab, using an induction-maintenance regimen, without cycle limitations of muzastotug.
• Phase 2 Trial Design: Up to 30 patients will be enrolled in each arm of the Phase 2 study, without a requirement for a muzastotug monotherapy arm.
• Phase 3 Trial Design: The FDA agreed with Adagene’s proposed standard-of-care (SOC) control arm for the Phase 3 clinical trial and confirmed that a muzastotug monotherapy arm was also not required.
• Phase 2 Endpoints: The primary endpoint of the Phase 2 trial will be overall response rate (ORR). Secondary endpoints include duration of response (DOR), progression-free survival (PFS), and overall survival (OS).
• Phase 3 Endpoints: The primary endpoint of the Phase 3 trial will be OS. Secondary endpoints will include PFS, DOR and ORR.

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, ADG126 (muzastotug), is a masked, anti-CTLA-4 SAFEbody that targets a unique epitope of CTLA-4 in regulatory T cells (Tregs) in the tumor microenvironment. ADG126 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.

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
LifeSci Advisors
cdavis@lifesciadvisors.com

Media Contact:
Lindsay Rocco
Elixir Health PR
862-596-1304
lrocco@elixirhealthpr.com

FAQ

What did Adagene (ADAG) announce on December 16, 2025 about muzastotug?

The company said the FDA granted Fast Track designation for muzastotug plus pembrolizumab in MSS mCRC patients without active liver metastases.

What is the primary endpoint of Adagene's Phase 2 muzastotug trial (ADAG)?

The Phase 2 primary endpoint is overall response rate (ORR), with secondary endpoints including DOR, PFS, and OS.

How are patients randomized in Adagene's Phase 2 muzastotug study?

Phase 2 will randomize late-line MSS CRC patients to 10 mg/kg or 20 mg/kg muzastotug with pembrolizumab, induction-maintenance regimen.

When is Adagene planning its muzastotug registration trial to begin?

Adagene plans for the registration trial to begin in 2027.

Does the FDA Fast Track for muzastotug speed up review for Adagene (ADAG)?

Fast Track enables more frequent FDA interactions and may allow a rolling review of future marketing applications.