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 November 2024
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 ¨
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.
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Adagene Inc. |
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By: |
/s/ Peter Luo |
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Name: |
Peter Luo |
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Title: |
Chief Executive Officer |
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| Date: November 7, 2024 |
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EXHIBIT INDEX
Exhibit 99.1
Adagene
Presents Two Posters with New Insights on Increased Therapeutic Index for Masked Anti-CTLA-4 SAFEbody® ADG126 (Muzastotug)
and Data Reinforcing Clinical Safety and Efficacy for ADG126 as Monotherapy and in Combination with Anti-PD-1 Therapy at Society for
Immunotherapy of Cancer (SITC) 39th Annual Meeting
- Improved
safety and efficacy profiles for ADG126 versus ipilimumab driven by precision masking, novel epitope-dependent antibody-dependent cellular
cytotoxicity (ADCC) and partial CTLA-4 blockade -
- Clinical
data show benefit of combining immune checkpoint inhibitors in MSS CRC and essential role of CTLA-4 to prime PD-L1 pathway -
- Clinical
poster selected by SITC as a ‘Top 100’ abstract out of 1439 regular abstracts -
SAN DIEGO and SUZHOU, China, Nov. 7, 2024-- Adagene Inc. (“Adagene”)
(Nasdaq: ADAG), a company transforming the discovery and development of novel antibody-based therapies, today announced data at the SITC
39th Annual Meeting, taking place in Houston, Nov. 6 – 10, 2024. The two poster presentations provide new insights
on the increased therapeutic index (TI) for ADG126 and reinforce its clinical safety and efficacy profiles in combination with pembrolizumab*
including in advanced Metastatic Microsatellite-stable (MSS) Colorectal Cancer (CRC).
“CTLA-4 has an essential role in harnessing the immune system
to improve outcomes for patients with cold and PD-L1 low or negative tumors, and CTLA-4 inhibition has been shown to prime T cells contributing
to enhanced combination therapy activity,” said Daneng Li, MD, Associate Professor in the Department of Medical Oncology &
Therapeutics Research at the City of Hope Comprehensive Cancer Center, and a study investigator. “With its increased
therapeutic index (TI), ADG126 has demonstrated in clinic that a unique epitope and masking technology can be deployed to deplete CTLA-4
mediated intratumoral T regulatory cells (Tregs), as anti-PD-1 alone has a minimum effect.”
In the first poster, Deciphering Improved Clinical Therapeutic
Index (TI) of Muzastotug (ADG126), a Masked Anti-CTLA-4 SAFEbody® over its Unmasked Form (ADG116) as Monotherapy
or in Combination with anti-PD-1 Therapy (toripalimab), data demonstrate how the improved TI of ADG126 allows for higher and
repeat dosing to unleash its efficacy to the maximum potential, while maintaining an improved safety profile. Analyses of the masked
ADG126 SAFEbody and its unmasked version, ADG116, show the improved TI relative to commercially available anti-CTLA-4 therapies (e.g.,
ipilimumab) via enhanced epitope-dependent ADCC and T cell priming. By targeting the constitutively over-expressed CTLA-4 on T regulatory
cells (Tregs) in the tumor microenvironment (TME) for potent CTLA-4 mediated intratumoral Treg depletion, ADG126 achieves tumor-specific
targeting with minimal on-target off-tumor toxicities.
Key highlights include:
| · | The
unique epitope of ADG126 and its activated form (ADG116) drives species cross-reactivity
enabling the same antibody to be used across mice, monkey and human studies, with a unified
set of physiologically relevant parameters for population pharmacokinetic (PK) modeling.
Analyses show a significantly higher and sustained steady state tumor-specific engagement
of CTLA-4 with the masked ADG126, suggesting increased exposure in the TME and a stronger
ADCC effect. |
| · | New
analyses show the seamless translation of preclinical PK analyses to clinical PK data, including: |
| o | head-to-head comparison of ADG126 to ipilimumab in MC38 mice (colon
cancer model), a single dose of ADG126 showed a three-fold increased active (e.g., cleaved)
drug exposure in homogenized tumor tissue samples at 10 mg/kg versus a single dose of ipilimumab
at 1 mg/kg while maintaining similar plasma active drug exposures. |
| o | A second analysis in the MC38 mice model showed two consecutive doses
of ADG126 at 20 mg/kg increased the tumor cleaved and total PK versus a single dose, demonstrating
continuous intratumoral cleavage of intact ADG126 and accumulation within the TME. This reflects
the effectiveness of ADG126 repeat dosing to increase drug exposure within the TME, supporting
its mechanism with CTLA-4 mediated intratumoral Treg depletion. |
The second poster, Phase 1b/2, Multicenter Dose Escalation and
Expansion Study of Muzastotug (ADG126, a Masked Anti-CTLA-4 SAFEbody®) in Combination with Pembrolizumab in Advanced/Metastatic
MSS CRCs, presents additional follow up data from an ongoing trial showing the best-in-class therapeutic potential of ADG126
in combination with anti-PD-1 therapy in patients with the most common form of colorectal cancer, MSS CRC.
The trial, conducted in patients with advanced MSS CRC without liver
metastases, showed that ADG126 administered at 10 mg/kg Q6W or Q3W in combination with pembrolizumab (200 mg/Q3W) demonstrated an
encouraging efficacy signal, durable disease control and an early survival benefit in MSS CRC patients, with dose-dependent efficacy
and objective responses per RECIST criteria observed for the Q3W schedule.
New findings in the poster at SITC 2024 include:
| · | In
MSS CRC patients, a lower rate of key TRAEs (i.e., diarrhea, colitis, etc.) with ADG126
at the 10 mg/kg dosing level in combination with pembrolizumab relative to lower doses of
1-2 mg/kg of an Fc engineered anti-CTLA-4 antibody in clinical development when used in combination
with anti-PD-1. Clinical PK, particularly the monitoring of active species of ADG126 in peripheral
blood, supports long-term safety of the combination therapy. |
| · | The
rate of Grade 3 and higher TRAEs for ADG126 in combination with pembrolizumab was also shown
to be much lower than historically reported with currently approved standard of care combinations.
In the combination cohort, there was no Grade 3 or higher colitis, which is common with other
anti-CTLA-4 therapies. |
| · | A
case study of one responder who received two prior lines of therapy before receiving ADG126
in combination with pembrolizumab showed an 80% decrease in target lesions (50 mm at baseline).
This confirmed partial response (PR) correlated with a 100% decrease in carcinoembryonic
antigen (CEA) levels versus baseline. Individualized PK data also demonstrated the correlation
of tumor shrinkage and plasma exposure. After five cycles, the patient experienced TRAEs,
after which dosing was modified and treatment resumed, showing durable clinical benefit for
over 12 months. This response is one of four PRs reported from the ongoing 10 mg/kg Q3W combination
cohort of MSS CRC patients without liver metastases (n=24). |
| · | Repeat
doses of ADG126 10 mg/kg in combination with pembrolizumab shows encouraging dose-dependent
clinical efficacy and well-tolerated safety in accordance with plasma cleaved ADG126 concentrations.
These data support that ADG126 may be a potential best-in-class anti-CTLA-4 and may be considered
as a backbone therapy. |
Follow up continues for MSS CRC patients treated with ADG126 10 mg/kg
doses in combination with pembrolizumab. In addition, Adagene is evaluating a single dose of ADG126 at 20 mg/kg followed by a 10 mg/kg
Q3W maintenance dose in combination with pembrolizumab in a cohort of 12 enrolled patients with data expected in 2025.
Poster Presentation Details
Both posters can be viewed during SITC on Saturday, November 9
at the George R. Brown Convention Center (Level 1, Exhibit Halls AB). They will also be available
on the Publications page of the company’s website here.
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 in
tumor microenvironment, 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 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 Twitter.
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.
Safe Harbor Statement
This press release contains forward-looking statements, including
statements regarding certain clinical results of ADG126, the potential implications of clinical data for patients, and Adagene’s
advancement of, and anticipated preclinical activities, clinical development, regulatory milestones, and commercialization of its product
candidates. Actual results may differ materially from those indicated in the forward-looking statements as a result of various important
factors, including but not limited to Adagene’s ability to demonstrate the safety and efficacy of its drug candidates; the clinical
results for its drug candidates, which may not support further development or regulatory approval; the content and timing of decisions
made by the relevant regulatory authorities regarding regulatory approval of Adagene’s drug candidates; Adagene’s ability
to achieve commercial success for its drug candidates, if approved; Adagene’s ability to obtain and maintain protection of intellectual
property for its technology and drugs; Adagene’s reliance on third parties to conduct drug development, manufacturing and other
services; Adagene’s limited operating history and Adagene’s ability to obtain additional funding for operations and to complete
the development and commercialization of its drug candidates; Adagene’s ability to enter into additional collaboration agreements
beyond its existing strategic partnerships or collaborations, and the impact of the COVID-19 pandemic on Adagene’s clinical development,
commercial and other operations, as well as those risks more fully discussed in the “Risk Factors” section in Adagene’s
filings with the U.S. Securities and Exchange Commission. All forward-looking statements are based on information currently available
to Adagene, and Adagene undertakes no obligation to publicly update or revise any forward-looking statements, whether
as a result of new information, future events or otherwise, except as may be required by law.
Investor & Media Contact:
Ami Knoefler
Adagene
650-739-9952
ir@adagene.com
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