Muzastotug Phase 2 dose expansion in MSS CRC with a 20 mg/kg loading dose regimen shows 33% overall response rate with four confirmed partial responses
SAFEbody technology utilized to create masked T cell engagers for potentially superior safety profile with enhanced therapeutic index
Cash balance of
“The clinical data we generated in 2024 with ADG126 gives us great confidence in our ability to provide patients with colorectal cancer a tolerable, efficacious treatment option. These data also provide the basis for us to expand our study in microsatellite stable colorectal cancer (MSS CRC) to include earlier lines of therapy and patients with liver metastases, a patient subpopulation that has historically seen little to no benefit from checkpoint inhibitors,” said
PIPELINE HIGHLIGHTS
ADG126 - Phase 1b/2 data:
- 20 mg/kg loading dose followed by 10 mg/kg Q3W in combination with pembrolizumab, Merck’s (known as MSD outside of the US and
Canada ) anti-PD-1 therapy, KEYTRUDA® (pembrolizumab), cohort achieved an improved ORR of 33%.- All responders remain on treatment at a maintenance dose of 10 mg/kg Q3W or 10 mg/kg Q6W in combination with pembrolizumab
- All responders remain on treatment at a maintenance dose of 10 mg/kg Q3W or 10 mg/kg Q6W in combination with pembrolizumab
- Good tolerability with a manageable safety profile for ADG126 + pembrolizumab combo, with overall low discontinuation rate (6%) for the MSS CRC expansion cohort. No Grade 4/5 safety events were seen to date.
- Based on robust safety data of ADG126 at 20 mg/kg Q6W in combination with pembrolizumab, the efficacy of this dosing regimen is being evaluated in the cohort expansion stage of the Phase 1b/2 trial.
- Company also plans to evaluate a broader patient population, including patients with liver metastases, by combining with standard of care medicines, a combination that has been limited by safety concerns in the past.
- Investigator initiated Phase 2 trial of ADG126 in neoadjuvant colorectal cancer to begin enrolling patients in April at the
National University Cancer Institute inSingapore
ADG138, a SAFEbody engineered T cell engager targeting HER2, has shown a wide therapeutic window and extended half-life for prolonged circulation in the tumor micro-environment in preclinical models. ADG138 is currently IND-ready.
ADG152, a SAFEbody engineered T cell engager targeting CD20, is designed to conditionally bind to CD20 on tumor cells and show negligible interaction with healthy cells, yielding a 100-fold reduction in cytokine release syndrome in preclinical models. ADG152 is currently in the IND-enabling phase.
The Company is pursuing strategic partnerships to advance the SAFEbody T cell engager programs.
ONGOING COLLABORATIONS
Exelixis: In
Sanofi:
Roche: Roche is sponsoring and conducting a phase 1b/2 multi-national trial to evaluate ADG126 in a triple combination with atezolizumab and bevacizumab in first-line hepatocellular carcinoma (HCC). To date, the combination has been well tolerated. Adagene retains global development and commercialization rights to ADG126.
2025 MILESTONES & CASH RUNWAY
Consistent with ongoing initiatives to prudently manage its cash balance,
- Provide longer-term time-to-event data from the existing Ph 1b/2 study of ADG126 + pembrolizumab in 3L+ MSS CRC
- Update 20 mg/kg loading dose cohort for durability of response (DOR and other time-to-event endpoints)
- Conduct EOP1 meeting with FDA by Q3 to obtain their endorsement on the proposed dose regimens, trial design and patient population
- Initiate evaluation of ADG126 + pembrolizumab in combination with standard of care in MSS CRC patients including those with liver metastases, beginning Q2
- Provide initial clinical data from investigator initiated Phase 2 trial for neoadjuvant ADG126 in colorectal cancer
- Establish additional collaboration/licensing agreements
CORPORATE UPDATES
JC Xu, M.D., Ph.D., Adagene’s Chief Strategy Officer and Head of Regulatory Affairs, has recently transitioned from a full-time employee of
Ms.
FINANCIAL HIGHLIGHTS
Cash and Cash Equivalents:
Cash and cash equivalents were
Net Revenue:
Net revenue was
Research and Development (R&D) Expenses:
R&D expenses were
Administrative Expenses:
Administrative expenses were
Other Operating Income, Net:
Other operating income, net was nil for the year ended
Net Loss:
Net loss attributable to Adagene Inc.’s shareholders was
Ordinary Shares Outstanding:
As of
Non-GAAP Net Loss:
Non-GAAP net loss, which is defined as net loss attributable to ordinary shareholders for the period after excluding share-based compensation expenses, was
Non-GAAP Financial Measures:
The company uses non-GAAP net loss and non-GAAP net loss per ordinary shares for the year, which are non-GAAP financial measures, in evaluating its operating results and for financial and operational decision-making purposes. The company believes that non-GAAP net loss and non-GAAP net loss per ordinary shares for the year help identify underlying trends in the company’s business that could otherwise be distorted by the effect of certain expenses that the company includes in its loss for the year. The company believes that non-GAAP net loss and non-GAAP net loss per ordinary shares for the year provide useful information about its results of operations, enhances the overall understanding of its past performance and future prospects and allows for greater visibility with respect to key metrics used by its management in its financial and operational decision-making.
Non-GAAP net loss and non-GAAP net loss per ordinary shares for the year should not be considered in isolation or construed as an alternative to operating profit, loss for the year or any other measure of performance or as an indicator of its operating performance. Investors are encouraged to review non-GAAP net loss and non-GAAP net loss per ordinary shares for the year and the reconciliation to their most directly comparable GAAP measures. Non-GAAP net loss and non-GAAP net loss per ordinary shares for the year here may not be comparable to similarly titled measures presented by other companies. Other companies may calculate similarly titled measures differently, limiting their usefulness as comparative measures to the company’s data. The company encourages investors and others to review its financial information in its entirety and not rely on a single financial measure. Non-GAAP net loss and non-GAAP net loss per ordinary shares for the year represent net loss attributable to ordinary shareholders for the year excluding share-based compensation expenses. Share-based compensation expense is a non-cash expense arising from the grant of stock-based awards to employees. The company believes that the exclusion of share-based compensation expenses from the net loss in the “Reconciliation of GAAP and Non-GAAP Results” assists management and investors in making meaningful period-to-period comparisons in the company's operating performance or peer group comparisons because (i) the amount of share-based compensation expenses in any specific period may not directly correlate to the company’s underlying performance, (ii) such expenses can vary significantly between periods as a result of the timing of grants of new stock-based awards, and (iii) other companies may use different forms of employee compensation or different valuation methodologies for their share-based compensation. Please see the “Reconciliation of GAAP and Non-GAAP Results” included in this press release for a full reconciliation of non-GAAP net loss and non-GAAP net loss per ordinary shares for the year to net loss attributable to ordinary shareholders for the year.
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 tates, 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 Contacts:
Raymond_tam@adagene.com
bmackle@lifesciadvisors.com
Unaudited Consolidated Balance Sheets
2023 |
2024 |
|||||
| US$ | US$ | |||||
| ASSETS | ||||||
| Current assets: | ||||||
| Cash and cash equivalents | 109,934,257 | 85,194,502 | ||||
| Amounts due from related parties | 222,027 | 8,309 | ||||
| Prepayments and other current assets | 3,287,445 | 2,575,194 | ||||
| Total current assets | 113,443,729 | 87,778,005 | ||||
| Property, equipment and software, net | 1,835,121 | 1,125,389 | ||||
| Operating lease right-of-use assets | 365,103 | 283,645 | ||||
| Other non‑current assets | 84,885 | 81,386 | ||||
| TOTAL ASSETS | 115,728,838 | 89,268,425 | ||||
| LIABILITIES AND SHAREHOLDERS’ EQUITY | ||||||
| Current liabilities: | ||||||
| Accounts payable | 3,093,752 | 4,241,773 | ||||
| Amounts due to related parties | 16,714,326 | 13,187,966 | ||||
| Accruals and other current liabilities | 3,001,508 | 2,816,038 | ||||
| Income tax payable | 52,884 | 5,265 | ||||
| Short‑term borrowings | 4,235,673 | 4,868,956 | ||||
| Current portion of long-term borrowings | 4,161,549 | 12,923,599 | ||||
| Current portion of operating lease liabilities | 195,955 | 141,341 | ||||
| Total current liabilities | 31,455,647 | 38,184,938 | ||||
| Long‑term borrowings | 13,540,034 | 417,339 | ||||
| Operating lease liabilities | 173,660 | 142,304 | ||||
| TOTAL LIABILITIES | 45,169,341 | 38,744,581 | ||||
| Commitments and contingencies | ||||||
| Shareholders’ equity: | ||||||
| Ordinary shares (par value of |
5,547 | 5,889 | ||||
| (4 | ) | — | ||||
| Additional paid‑in capital | 350,105,518 | 362,220,445 | ||||
| Accumulated other comprehensive loss | (1,800,088 | ) | (526,903 | ) | ||
| Accumulated deficit | (277,751,476 | ) | (311,175,587 | ) | ||
| Total shareholders’ equity | 70,559,497 | 50,523,844 | ||||
| TOTAL LIABILITIES AND SHAREHOLDERS’ EQUITY | 115,728,838 | 89,268,425 |
Unaudited Consolidated Statements of Comprehensive Loss
| For the Year Ended |
For the Year Ended |
|||||
| US$ |
US$ | |||||
| Revenues | ||||||
| Licensing and collaboration revenue | 18,111,491 | 103,204 | ||||
| Operating expenses and income | ||||||
| Research and development expenses | (36,639,146 | ) | (28,781,412 | ) | ||
| Third parties | (33,978,642 | ) | (26,837,889 | ) | ||
| Related parties | (2,660,504 | ) | (1,943,523 | ) | ||
| Administrative expenses | (8,672,843 | ) | (7,273,335 | ) | ||
| Other operating income, net | 3,480,632 | — | ||||
| Loss from operations | (23,719,866 | ) | (35,951,543 | ) | ||
| Interest and investment income | 4,283,085 | 3,801,345 | ||||
| Interest expense | (1,107,820 | ) | (851,874 | ) | ||
| Other income, net | 1,843,437 | 466,620 | ||||
| Foreign exchange gain (loss), net | 1,446,202 | (906,212 | ) | |||
| Loss before income tax | (17,254,962 | ) | (33,441,664 | ) | ||
| Income tax benefit (expense) | (1,691,408 | ) | 17,553 | |||
| Net loss attributable to Adagene Inc.’s shareholders | (18,946,370 | ) | (33,424,111 | ) | ||
| Other comprehensive income (loss) | ||||||
| Foreign currency translation adjustments, net of nil tax | (950,783 | ) | 1,273,185 | |||
| Total comprehensive loss attributable to Adagene Inc.’s shareholders | (19,897,153 | ) | (32,150,926 | ) | ||
| Net loss attributable to Adagene Inc.’s shareholders | (18,946,370 | ) | (33,424,111 | ) | ||
| Net loss attributable to ordinary shareholders | (18,946,370 | ) | (33,424,111 | ) | ||
| Weighted average number of ordinary shares used in per share calculation: | ||||||
| —Basic | 54,737,530 | 56,287,903 | ||||
| —Diluted | 54,737,530 | 56,287,903 | ||||
| Net loss per ordinary share | ||||||
| —Basic | (0.35 | ) | (0.59 | ) | ||
| —Diluted | (0.35 | ) | (0.59 | ) | ||
Reconciliation of GAAP and Non-GAAP Results
| For the Year Ended |
For the Year Ended |
|||||
| US$ |
US$ | |||||
| GAAP net loss attributable to ordinary shareholders | (18,946,370 | ) | (33,424,111 | ) | ||
| Add back: | ||||||
| Share-based compensation expenses | 7,271,700 | 4,909,573 | ||||
| Non-GAAP net loss | (11,674,670 | ) | (28,514,538 | ) | ||
| Weighted average number of ordinary shares used in per share calculation: | ||||||
| —Basic | 54,737,530 | 56,287,903 | ||||
| —Diluted | 54,737,530 | 56,287,903 | ||||
| Non-GAAP net loss per ordinary share | ||||||
| —Basic | (0.21 | ) | (0.51 | ) | ||
| —Diluted | (0.21 | ) | (0.51 | ) | ||
Source: Adagene Inc.