- Clinical data for wholly-owned anti-CTLA-4 franchise show best-in-class safety profiles for unmasked and masked candidates, unlocking the full therapeutic benefit of anti-CTLA-4 in combination with anti-PD-1 and beyond -
- Roche sponsoring randomized, multi-national phase 1b/2 trial of novel triple combination therapy in first-line liver cancer, leveraging safety profile of masked, anti-CTLA-4 SAFEbody® ADG126 -
- Sanofi and Exelixis collaborations present multi-billion dollar opportunity for non-dilutive funding via milestones and royalties -
- Cash balance of
“We are investing in R&D activities to strengthen the differentiation and impact of our anti-CTLA-4 franchise, while generating non-dilutive funding through collaborations,” said
PIPELINE & BUSINESS HIGHLIGHTS
Anti-CTLA-4 Programs
- Phase 1b/2 data for ADG116, an unmasked anti-CTLA-4 NEObody™ targeting a unique epitope showed a differentiated safety profile and anti-tumor activity, both in monotherapy and in combination with anti-PD-1:
- In monotherapy studies of 50 patients with advanced/metastatic tumors, ADG116 was administered up to 15 mg/kg every three weeks with repeat dosing.
- No Grade 3 or higher treatment-related adverse events (TRAEs) were reported at the 15 mg/kg dose level, while Grade 3 or higher TRAEs at 10 mg/kg (13%) were lower than the reported rate (36%) for a currently approved anti-CTLA-4 therapy, ipilimumab, at 10 mg/kg in first-line monotherapy in melanoma patients in a non-head-to-head comparison.
- ADG116 monotherapy in heavily pre-treated patients with difficult-to-treat tumors resulted in two partial responses in Kaposi’s sarcoma and renal cell carcinoma. In
February 2023 , a third partial response with monotherapy was reported in a patient with MSI-H endometrial cancer. The patient had received five cycles of ADG116 at 10 mg/kg with only Grade 1 TRAEs reported. - ADG116 in combination with anti-PD-1 therapies also demonstrated a differentiated safety profile and anti-tumor activity at 3 mg/kg with repeat dosing. Results were presented at the Society for Immunotherapy of Cancer’s (SITC) annual meeting, including one confirmed, durable complete response observed after six cycles in a patient with platinum-refractory recurrent head and neck squamous cell carcinoma who remains on therapy (n=5; ORR = 20%; DCR = 100%). Additionally, a significant reduction in a tumor-related biomarker (carcinoembryonic antigen levels) was observed in two patients with metastatic microsatellite-stable (MSS) colorectal cancer (CRC); both patients had either liver or lung metastases.
- Combination dose expansion of ADG116 in combination with anti-PD-1 is ongoing for dose optimization.
- Phase 1b/2 data for ADG126, a masked anti-CTLA-4 SAFEbody targeting a unique epitope, showed compelling safety and promising efficacy profiles at high dose levels with repeat dosing both in monotherapy and in combination with anti-PD-1:
- In dose escalation, ADG126 monotherapy was well tolerated with no dose-limiting toxicities or Grade 3 or higher TRAEs observed when administered up to 20 mg/kg every three weeks with repeat dosing in 26 patients with advanced/metastatic solid tumors.
- Clinical evaluation with anti-PD-1 therapies is ongoing with interim data from dose escalation portions of phase 1b/2 trials in combination with toripalimab and pembrolizumab to be presented at the upcoming
American Association for Cancer Research annual meetingApril 14 – 18, 2023 inOrlando, Florida . - Interim results announced in
January 2023 from ongoing phase 1b/2 trials of ADG126 in combination with anti-PD-1 therapy include:- No dose-limiting toxicities observed when ADG126 combined up to 10 mg/kg with repeat cycles, highlighting the potential of SAFEbody anti-CTLA-4 therapy. SAFEbody ADG126 provides systemic delivery of CTLA-4 treatment similar to intra-tumoral delivery to reach a higher concentration at the tumor site, enabling concentration-dependent, intra-tumoral Treg depletion for effective immunotherapy.
- Multiple partial responses were confirmed in several tumor types during combination dose escalation.
- Continuous tumor shrinkage in cold tumors and anti-PD-1 resistant patients.
- Efficacy results consistent with data for parental antibody (ADG116) in warm and cold tumors due to its strong intra-tumoral depletion of regulatory T cells in the tumor microenvironment (TME).
- Dose expansion for ADG126 in combination with anti-PD-1 is ongoing with multiple dosing regimens being evaluated, in alignment with the Food & Drug Administration’s Project Optimus for dose optimization of cancer drugs.
Additional Clinical & Preclinical Programs
- Initiated dosing of the first patient in a phase 1 trial evaluating safety, efficacy and tolerability profiles for ADG206, a masked, IgG1 FC-enhanced anti-CD137 POWERbody™ in patients with advanced/metastatic tumors. This next generation anti-CD137 candidate is the first POWERbody candidate to advance into clinic, combining precision masking, Fc-engineering and targeting of a unique epitope to solve the safety and efficacy challenges of anti-CD137 therapies.
- Continued investigator-initiated trials (IITs) for ADG106, an anti-CD137 agonist NEObody, in selected combination settings, including advanced non-small cell lung cancer (NSCLC) and early-stage, HER2-negative breast cancer.
- Presented best-in-class profiles for multiple preclinical product candidates in IND-enabling studies, including ADG153 (anti-CD47 IgG1 SAFEbody) and ADG138 (HER2xCD3 POWERbody), which apply SAFEbody precision masking technology. The robust preclinical profiles for these and other product candidates are published here.
- Proprietary bispecific T-cell engager (TCE) capability with CD28 designed to mitigate the serious safety concerns of CD28 activation. CD28 bispecific POWERbody TCEs in preclinical evaluation exhibit enormous potential to fulfill the promise of safe and durable T cell-mediated synergistic immunotherapies when combined with CD3 bispecific TCEs and/or checkpoint inhibitors. The full poster presentation may be viewed here.
Collaborations
- Roche: Established a clinical trial collaboration in
December 2022 where Roche will sponsor and conduct a randomized phase 1b/2 multi-national trial to evaluate the efficacy, safety and pharmacokinetic profiles of ADG126 in a triple combination with bevacizumab and atezolizumab, versus the approved combination of atezolizumab and bevacizumab alone in first-line hepatocellular carcinoma (HCC). Each company is supplying its respective anti-cancer agent(s) to support the trial, which will be initially conducted in 60 patients. The trial reflects Roche’s leadership and commitment to HCC, where they pioneered the established standard-of-care doublet combination, and validates Adagene’s differentiated ADG126 anti-CTLA-4 clinical program. Adagene will retain global development and commercialization rights to ADG126. - Sanofi: Established a technology licensing agreement with Sanofi in
March 2022 to generate masked versions of antibodies provided by Sanofi, including monoclonal and bispecific candidate antibodies, with a potential transaction value ofUS$2.5 billion . The collaboration included an upfront payment ofUS$17.5 million received inApril 2022 for the initial two programs (US$8.75 million per program), an option fee for two additional programs, potential milestone payments of up toUS$2.5 billion (US$625 million per program), and tiered royalties. - Exelixis: Received a
US$3.0 million milestone payment from Exelixis inJanuary 2022 for the successful nomination of lead SAFEbody candidates for one of the collaboration programs and an additional$1.1 million upfront payment for an expanded collaboration in SAFEbody discovery inJune 2022 , based on a technology licensing agreement to develop novel masked antibody-drug conjugate candidates. Terms of the agreement, which was executed inFebruary 2021 , include an upfront payment ofUS$11 million for two programs, potential milestones and tiered royalties. China : Advanced global partnerships and collaboration with Sanjin and Dragon Boat Biopharmaceutical for two antibodies out-licensed inGreater China , including an anti-PD-L1 (ADG104) in phase 2 and a novel anti-CSF-1R (ADG125/BC006) in phase 1 development.
CORPORATE UPDATES
- In
March 2023 , appointed Professor Aurélien Marabelle, MD, PhD, to the company’sScientific and Strategic Advisory Board . Professor Marabelle is a physician-scientist with expertise in oncology and immunology working within theDrug Development Department (DITEP) ofGustave Roussy Cancer Center inFrance . Professor Marabelle brings deep insight in tumor-specific Treg depletion for anti-CTLA-4 therapies delivered intra-tumorally to overcome dose dependent toxicities through systemic delivery of anti-CTLA-4 therapies. - In
November 2022 , appointed Cuong Do, MBA, to the company’s board of directors as an independent director. He also serves as an audit committee member and will be chairing a strategy committee of the board. Mr. Do is President and CEO of BioVie Inc., a clinical-stage company developing innovative drug therapies. He was previously the Chief Strategy Officer for Merck, a leading global pharmaceuticals company, where he played a key role in defining the company’s strategy, including the focus on oncology and creating its leading position with the anti-PD-1 therapy, pembrolizumab.
UPDATED MILESTONES & OUTLOOK
Following initiatives to streamline its operations over the past year, Adagene expects its cash balance to sufficiently fund activities into 2025, with the following milestones during 2023:
- Establish registration path and strategy (e.g., recommended phase 2 dose, indication and design) for phase 2/3 pivotal trial of anti-CTLA-4 in combination with anti-PD-1 therapy in targeted tumors
- ADG126 phase 2 proof-of-concept data from combination dose expansion cohorts
- Advance ADG116 phase 2 combination dose expansion cohorts
- Providing the path to a potential registrational trial for triple combination with Roche’s atezolizumab/bevacizumab, advance ADG126 randomized phase 1b/2 trial in first-line hepatocellular carcinoma (HCC) conducted by Roche; provide update on trial status.
- Advance ADG206 phase 1 trial (masked, FC enhanced, IgG1 anti-CD137) and advance IND-enabling programs as resources allow.
- Additional collaborations and/or technology licensing agreements.
FINANCIAL HIGHLIGHTS
Cash and Cash Equivalents:
Cash and cash equivalents were
Total non-dilutive funding received from business development collaborations increased to
Net Revenue:
Net revenue was
Research and Development (R&D) Expenses:
R&D expenses were
Administrative Expenses:
Administrative expenses were
Net Loss:
The net loss attributable to Adagene Inc.’s shareholders was
Non-GAAP Net Loss:
Non-GAAP net loss, which is defined as net loss attributable to ordinary shareholders for the period after excluding (i) share-based compensation expenses and (ii) accretion of convertible redeemable preferred shares to redemption value, as applicable, 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 (i) share-based compensation expenses, and (ii) accretion of convertible redeemable preferred shares to redemption value. 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/period.
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 unmet patient needs. 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. Adagene has forged strategic collaborations with reputable global partners that leverage its technology in multiple approaches at the vanguard of science.
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.
Safe Harbor Statement
This press release contains forward-looking statements, including statements regarding 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 annual report for the year of 2021 on Form 20-F filed with the
FINANCIAL TABLES FOLLOW
Unaudited Consolidated Balance Sheets
2021 |
2022 |
|||
| US$ | US$ | |||
| ASSETS | ||||
| Current assets: | ||||
| Cash and cash equivalents | 174,391,243 | 143,758,678 | ||
| Accounts receivable, net | 3,000,000 | — | ||
| Amounts due from related parties | 4,506,670 | 619,432 | ||
| Prepayments and other current assets | 4,055,921 | 4,937,323 | ||
| Total current assets | 185,953,834 | 149,315,433 | ||
| Property, equipment and software, net | 3,487,617 | 2,782,963 | ||
| Operating lease right-of-use assets | — | 191,877 | ||
| Other non-current assets | 69,275 | 109,572 | ||
| TOTAL ASSETS | 189,510,726 | 152,399,845 | ||
| LIABILITIES AND SHAREHOLDERS’ EQUITY | ||||
| Current liabilities: | ||||
| Accounts payable | 3,321,615 | 3,666,124 | ||
| Contract liabilities | 5,500,000 | 15,107,276 | ||
| Amounts due to related parties | 10,466,061 | 19,323,337 | ||
| Accruals and other current liabilities | 4,379,243 | 3,212,809 | ||
| Income tax payable | 1,657,450 | — | ||
| Short-term borrowings | 3,121,226 | 10,768,745 | ||
| Current portion of long-term borrowings | 1,376,319 | 2,850,128 | ||
| Current portion of operating lease liabilities | — | 151,983 | ||
| Total current liabilities | 29,821,914 | 55,080,402 | ||
| Long-term borrowings | 2,991,829 | 14,146,541 | ||
| Operating lease liabilities | — | 53,834 | ||
| Deferred tax liabilities | 44,163 | — | ||
| Other non-current liabilities | 94,107 | 28,718 | ||
| TOTAL LIABILITIES | 32,952,013 | 69,309,495 | ||
| Commitments and contingencies | ||||
| Shareholders’ equity: | ||||
| Ordinary shares | 5,627 | 5,497 | ||
| (619,605 | ) | (4 | ) | |
| Additional paid-in capital | 336,099,931 | 342,739,268 | ||
| Accumulated other comprehensive income (loss) | (93,981 | ) | (849,305 | ) |
| Accumulated deficit | (178,833,259 | ) | (258,805,106 | ) |
| Total shareholders’ equity | 156,558,713 | 83,090,350 | ||
| TOTAL LIABILITIES AND SHAREHOLDERS’ EQUITY | 189,510,726 | 152,399,845 | ||
Unaudited Consolidated Statements of Comprehensive Loss
| For the Year Ended |
For the Year Ended |
|||
| US$ | US$ | |||
| Revenues | ||||
| Licensing and collaboration revenue | 10,175,258 | 9,292,724 | ||
| Expenses | ||||
| Research and development expenses | (68,099,385 | ) | (81,339,540 | ) |
| Third parties | (55,020,367 | ) | (46,212,077 | ) |
| Related parties | (13,079,018 | ) | (35,127,463 | ) |
| Administrative expenses | (14,439,962 | ) | (11,873,867 | ) |
| Loss from operations | (72,364,089 | ) | (83,920,683 | ) |
| Interest income | 76,166 | 377,501 | ||
| Interest expense | (363,762 | ) | (693,323 | ) |
| Other income, net | 1,778,822 | 2,168,388 | ||
| Foreign exchange gain (loss), net | (603,459 | ) | 2,555,325 | |
| Loss before income tax | (71,476,322 | ) | (79,512,792 | ) |
| Income tax expense | (1,701,613 | ) | (459,055 | ) |
| Net loss attributable to Adagene Inc.’s shareholders | (73,177,935 | ) | (79,971,847 | ) |
| Other comprehensive income (loss) | ||||
| Foreign currency translation adjustments, net of nil tax | 257,000 | (755,324 | ) | |
| Total comprehensive loss attributable to Adagene Inc.’s shareholders | (72,920,935 | ) | (80,727,171 | ) |
| Net loss attributable to Adagene Inc.’s shareholders | (73,177,935 | ) | (79,971,847 | ) |
| Accretion of convertible redeemable preferred shares to redemption value | (28,553 | ) | — | |
| Net loss attributable to ordinary shareholders | (73,206,488 | ) | (79,971,847 | ) |
| Weighted average number of ordinary shares used in per share calculation: | ||||
| —Basic | 50,032,009 | 54,135,084 | ||
| —Diluted | 50,032,009 | 54,135,084 | ||
| Net loss per ordinary share | ||||
| —Basic | (1.46 | ) | (1.48 | ) |
| —Diluted | (1.46 | ) | (1.48 | ) |
Reconciliation of GAAP and Non-GAAP Results
| For the Year Ended |
For the Year Ended |
|||
| US$ | US$ | |||
| GAAP net loss attributable to ordinary shareholders | (73,206,488 | ) | (79,971,847 | ) |
| Add back: | ||||
| Share-based compensation expenses | 18,679,658 | 10,520,282 | ||
| Accretion of convertible redeemable preferred shares to redemption value | 28,553 | — | ||
| Non-GAAP net loss | (54,498,277 | ) | (69,451,565 | ) |
| Weighted average number of ordinary shares used in per share calculation: | ||||
| —Basic | 50,032,009 | 54,135,084 | ||
| —Diluted | 50,032,009 | 54,135,084 | ||
| Non-GAAP net loss per ordinary share | ||||
| —Basic | (1.09 | ) | (1.28 | ) |
| —Diluted | (1.09 | ) | (1.28 | ) |
Investor & Media Contact:Ami Knoefler 650-739-9952 ir@adagene.com
Source: Adagene Inc.