Urelumab

– Topline data for anti-CTLA-4 antibody, ADG116, shows compelling clinical safety and complete and partial responses as both a single agent and in combination with anti-PD-1 therapy; results to be presented at SITC 2022 – – Masked, anti-CTLA-4 antibody, ADG126, safely dosed repeatedly up to 20 mg/kg as a single agent with encouraging efficacy signals; results to be presented at ESMO 2022 – – Presentation of combination dosing data with anti-PD-1 therapies in 2022, while dose expansion begins for both ADG116 and ADG126 in targeted tumors – – Submitted regulatory filing for clinical trial of masked, IgG1-based anti-CD137 candidate, ADG206, with greater preclinical potency than the analog of a benchmark antibody, urelumab, that demonstrated monotherapy efficacy in clinic; patient dosing planned in early 2023 – – Cash balance of US$168 million supports streamlined operations into late 2024, with planned key readouts in 2023 for anti-CTLA-4 and anti-PD-1 combination therapies expected to pave way for pivotal trials – – Technology licensing collaborations provide near-term revenue opportunity – SAN DIEGO and SUZHOU, China, Aug. 30, 2022 (GLOBE NEWSWIRE) -- Adagene Inc. (“Adagene”) (Nasdaq: ADAG), a platform-driven, clinical-stage biotechnology company transforming the discovery and development of novel antibody-based therapies, today reported financial results for the six months ended June 30, 2022 and provided corporate updates. “We are prioritizing development of two anti-CTLA-4 antibodies, which have best-in-class profiles and are on track to deliver proof-of-concept clinical results in combination therapy in 2023. Anti-CTLA-4 therapy is known for dose dependent toxicity, making it extremely difficult to optimize dosing levels, dosing frequency and dosing intervals for prevailing anti-CTLA-4 therapy, especially in combination therapy with anti-PD-1. We have solved this problem with differentiated candidates suitable for the massive market opportunity for next generation anti-CTLA-4 therapies, increasing market penetration into known and new indications with enhanced safety and efficacy, especially for tumor types not addressed with the currently available therapy, and rapid entry into new markets such as China with few approved indications for anti-CTLA-4 in combination with widely accessible anti-PD-1 therapy,” said Peter Luo, Ph.D., Co-founder, Chief Executive Officer and Chairman of Adagene. “We are also excited to advance our next generation anti-CD137 agonistic antibody, ADG206, into clinic given its first- and best-in-class potential in both monotherapy and in combination with multiple agents.” Dr. Luo continued: “On the longer-term horizon, we have developed a portfolio of masked, bispecific T cell engagers (TCEs) for tumor directed T cell therapies, armed with proprietary, tailor-made anti-CD3 and CD28 by leveraging our NEObody™ and SAFEbody® technologies, that aim to push the boundaries of what is possible with TCEs – to achieve safe, potent and durable responses for patients by combining our novel modalities with the fundamental pathways across the cancer immunity cycle.” He concluded: “Building on success of existing technology licensing deals, we are also pursuing additional collaboration agreements that leverage our pipeline, our integrated AI-powered antibody discovery platform, and our SAFEbody precision masking technology, to bring potential non-dilutive funding to Adagene. We believe that the combination of our proprietary technology platforms and our highly differentiated clinical and preclinical pipelines presents us with many value-creating levers to navigate today’s turbulent financial markets.” PIPELINE & BUSINESS HIGHLIGHTS ADG116 (anti-CTLA-4 NEObody™ targeting a unique epitope) Encouraging efficacy demonstrated as a single agent and in combination with anti-PD-1: Observed one partial response with ADG116 monotherapy in a tumor type where no anti-CTLA-4 therapy is currently approved.Observed one confirmed rapid complete response with repeat dosing for ADG116 in combination with toripalimab in a tumor type where no anti-CTLA-4 therapy is currently approved.Presentation of data from this phase 1b/2 trial will take place at the Society for Immunotherapy of Cancer’s 37th Annual Meeting (SITC 2022) in Boston, November 8-12, 2022.For competitive reasons, Adagene is currently not disclosing the dose or tumor types of these objective responses. Compelling safety demonstrated as a single agent and in combination with anti-PD-1: Completed monotherapy dose escalation of ADG116 in 30 patients up to 15 mg/kg administered every three weeks with repeat dosing, and continued to enroll patients in dose expansion at 10 mg/kg.Only one dose-limiting toxicity event reported at ESMO-IO 2021 for the 10 mg/kg dose. As of this release, no additional or late-onset dose-limiting toxicities reported with ADG116 monotherapy, including in patients who received more than four cycles.A safety review committee cleared advancement to dose expansion with 3 mg/kg of ADG116 for combination cohorts with toripalimab. Continued advancement of combinations with anti-PD-1 or anti-CD137: Completing dose escalation of ADG116 in combination with the anti-PD-1 antibody, pembrolizumab (ADG116-P001 / KEYNOTE-C97). Presentation of data from this phase 1b/2 trial will take place at SITC 2022.Evaluation ongoing of ADG116 in combination with the anti-CD137 therapy, ADG106, to optimize the dose and schedule for this novel, proprietary combination. Adagene is a global leader in exploring the synergistic clinical effects for the dual pathway targeting CTLA-4 and CD137 given the compelling preclinical rationale for this powerful combination.Paving the way for combination trials in China, advanced dose escalation to 10 mg/kg in phase 1 monotherapy trial (ADG116-1002). A significant untapped clinical and market opportunity exists for the proven combination of anti-CTLA-4 and anti-PD-1 therapies as the combination is only approved in one tumor type in China. ADG126 (anti-CTLA-4 SAFEbody® targeting a unique epitope with precision masking) Compelling clinical safety demonstrated at unprecedented dosing levels with repeat dosing: Completed monotherapy dose escalation of ADG126 in 19 patients up to 20 mg/kg administered every three weeks with repeat dosing, and continued to enroll patients in dose expansion at 10 mg/kg.ADG126 monotherapy was well tolerated with no dose-limiting toxicities or treatment-related serious adverse events observed following repeat dosing across all dose levels, as reported in an abstract at the 2022 American Society of Clinical Oncology annual meeting.Clinical evaluation with anti-PD-1 therapies is ongoing to establish the dose and schedule for phase 2 combination cohorts. In combination cohorts with toripalimab, the safety review committee has cleared the 6 mg/kg dose administered every three weeks, approved dose expansion at 6 mg/kg, and recommended further dose escalation to 10 mg/kg, the highest dose level ever reported for the combination of anti-CTLA-4 and anti-PD-1 therapies. Encouraging antitumor activity observed as monotherapy in cold tumors: In a cohort of heavily pre-treated patients, ADG126 monotherapy resulted in durable reductions in target lesions over 20% in two patients with cold tumors: One ovarian cancer patient who experienced significant, continued reduction of an established ovarian cancer biomarker, CA125, dropping 90% to within the normal range for full clinical benefit after receiving up to 18 cycles of treatment at 1 mg/kg, as of this release.One uveal melanoma patient who received prior immuno-oncology treatment, having progressed after the combination of nivolumab and ipilimumab.Updated interim results will be presented in a poster on September 12 at the European Society for Medical Oncology (ESMO) Congress 2022 in Paris, September 9 – 13, 2022 Both monotherapy and combination trials continue to enroll patients with advanced, metastatic tumors in the US, China and APAC, evaluating optimized doses of ADG126 in targeted tumors. Pharmacokinetics show effectiveness of precision masking technology: In monotherapy evaluation, ADG126 plasma pharmacokinetics (PK) were approximately linear and activated ADG126 accumulated steadily during repeat dosing across different dose levels.This reflects prolonged exposures of activated ADG126 in the tumor microenvironment (TME), with cleaved ADG126 in plasma on average accumulating >2-fold during repeat dosing. ADG106 (agonistic anti-CD137 NEObody™) Given prioritization of anti-CTLA-4 programs, combination trial with toripalimab in China is winding down: Results from the phase 1b/2 trial (ADG106-1008) in China evaluating ADG106 in combination with toripalimab, showed one observed partial response in a nasopharyngeal carcinoma (NPC) patient out of 20 patients enrolled. Currently, four patients remain on therapy.Given prioritization of its two anti-CTLA-4 clinical programs and potential of its next generation anti-CD137 therapy, ADG206, Adagene is winding down the ADG106-1008 trial and does not intend to proceed with the previously planned trial of ADG106 and pembrolizumab. Focusing clinical development on investigator-initiated trials (IITs) in selected indications: Reflecting its strategic presence and collaborations in Singapore, Adagene continues to support the ongoing IITs in Singapore and explore the anti-CD137 opportunity with ADG106 in selected indications in a combination setting, including: An ongoing phase 1b/2 clinical trial (ADG106-T6001) evaluating ADG106 in combination with the anti-PD-1 antibody, nivolumab, for patients with advanced non-small cell lung cancer (NSCLC) who have progressed after prior treatment. Dose escalation is complete and dose expansion is ongoing.An ongoing Phase 1b/2 clinical trial (ADG106-T6002) evaluating ADG106 in combination with neoadjuvant chemotherapy (doxorubicin and cyclophosphamide followed by paclitaxel) in patients with early-stage, HER2 negative breast cancer. ADG206 (masked, IgG1 FC engineered anti-CD137 POWERbody™) On track for clinical development as a next generation anti-CD137 candidate that combines masking, Fc-engineering and novel epitope to deliver balance between safety and efficacy: Adagene submitted a Human Research Ethics Committee (HREC) regulatory filing in Australia to advance this anti-CD137 POWERbody™, ADG206, into a phase 1 clinical trial in patients with advanced metastatic solid tumors.Patient dosing is planned in early 2023.ADG206 is designed to solve the safety and efficacy challenges of anti-CD137 therapy, leveraging the same novel epitope as ADG106 and learnings from development of urelumab (another company’s anti-CD137 targeting antibody), which showed single agent clinical efficacy and dose-dependent liver toxicity in clinic.Preclinical data demonstrated that ADG206 was well tolerated and had robust anti-tumor activity as a single agent in multiple tumor models, with approximately 4-fold stronger anti-CD137 agonistic activity of its activated form than a urelumab analog; ADG206 also demonstrated enhanced anti-tumor activity in combination with other agents, including checkpoint inhibitors and anti-CTLA-4 therapy. Preclinical Discovery Programs ADG153: Given updated program timelines and ongoing business development activities, Adagene now plans the regulatory submission for its masked, IgG1 anti-CD47 SAFEbody, ADG153, in the first half of 2023. This candidate is differentiated by its strong antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP) activity designed to realize the full potential of anti-CD47 therapy for both hematologic and solid tumor indications. Preclinical data demonstrated that ADG153 IgG1 was well tolerated, did not induce human hemagglutination and significantly reduced anemia-related and antigen sink liabilities; ADG153 IgG1 also demonstrated greater anti-tumor activity than the benchmark (magrolimab analog).American Association for Cancer Research (AACR) Annual Meeting 2022: Data demonstrated the potential best-in-class profiles for three differentiated preclinical product candidates in IND-enabling studies (ADG206, ADG153, ADG138), which all apply SAFEbody precision masking technology. The robust preclinical poster presentations for these and other product candidates are available on the Publications page of the company’s website.CD28 T-cell engagers (TCEs): Data at AACR introduced a new capability for Adagene’s proprietary bispecific TCEs with CD28. CD28 bispecific POWERbody TCEs exhibit enormous potential to fulfill the promises of safe and durable T cell-mediated synergistic immunotherapies when combined with CD3 bispecific TCEs and/or checkpoint inhibitors. Preclinical data demonstrated the potential to mitigate the serious safety concerns of CD28 activation and make custom designed antibodies targeting a highly conserved epitope with broad species reactivity. Multiple tumor associated antigen (TAA) x CD28 POWERbodies are in progress, such as B7-H3xCD28 and TROP2xCD28, which can also be combined with the company’s CD3 TCEs and/or checkpoint inhibitors to achieve safe, powerful and durable immunotherapy for solid tumors. The full poster presentation may be viewed here. Collaborations 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 of US$2.5 billion. The collaboration includes an upfront payment of US$17.5 million received in April 2022 for the initial two programs (US$8.75 million per program), an option fee for two additional programs, potential milestone payments of up to US$2.5 billion (US$625 million per program), and tiered royalties.Exelixis: Received a US$3.0 million milestone payment from Exelixis in January 2022 for the successful nomination of lead SAFEbody candidates for one of the collaboration programs and an additional $1.1 million upfront payment in June 2022, based on a technology licensing agreement to develop novel masked antibody-drug conjugate candidates. Terms of the agreement, which was executed in February 2021, include an upfront payment of US$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 in Greater China, including an anti-PD-L1 (ADG104) in phase 2 development, and a novel anti-CSF-1R (ADG125/BC006) in phase 1. Corporate Adagene is making progress to evaluate business processes that meet the requirements of the Holding Foreign Companies Accountable Act (HFCAA) and the Accelerating Holding Foreign Companies Accountable Act (AHFCAA) in the event that AHFCAA becomes enacted prior to the filing of annual report for the year of 2023 on Form 20-F. The company is closely monitoring the status and implications of HFCAA and AHFCAA in order to take decisive action to minimize its impact on the company.Adagene continues to streamline its operations while focusing on its most advanced and promising clinical and preclinical programs to reduce its cash burn. UPDATED MILESTONES & OUTLOOK Adagene is updating its business outlook to reflect prioritization of its anti-CTLA-4 clinical development programs and achievement of meaningful milestones with its current cash resources. Based on current plans, Adagene expects its cash balance to sufficiently fund operations into late 2024, with the following upcoming milestones: 2022 Present ADG126 monotherapy dose escalation data at ESMO 2022Present additional ADG116 data at SITC 2022ADG116 results of dose escalation in combination with anti-PD-1 therapy to establish the dose(s) and schedule(s) for dose expansion; advance phase 2a dose expansion cohorts in targeted tumorsADG126 results of dose escalation in combination with anti-PD-1 therapy to establish the dose(s) and schedule(s) for dose expansion; advance phase 2a dose expansion cohorts in targeted tumors 2023 ADG116 phase 2a proof-of-concept data from combination dose expansion cohortsADG126 phase 2a proof-of-concept data from combination dose expansion cohortsEstablish 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 tumorsInitiate patient dosing in ADG206 phase 1 trialSubmit IND or equivalent for ADG153, and initiate phase 1 trialResults from IIT combination studies of ADG106Additional collaborations and/or technology licensing agreements FINANCIAL HIGHLIGHTS Cash and Cash Equivalents:Cash and cash equivalents were US$168.0 million as of June 30, 2022, compared to US$174.4 million as of December 31, 2021. The 2022 cash balance includes an upfront payment of US$17.5 million from Sanofi, and a milestone payment of US$3.0 million and upfront payment of US$1.1 million from Exelixis, related to Adagene’s respective collaboration and technology licensing agreements with those companies. Net Revenue:Net revenue was US$3.9 million for the six months ended June 30, 2022, compared to US$1.4 million for the same period in 2021. The increase was related to revenue recognized due to fulfillment of performance obligations over time associated with the collaboration and technology licensing agreement with Sanofi to develop antibody-based therapies. Due to the Sanofi and Exelixis collaborations, contract liabilities also increased to US$20.2 million as of June 30, 2022, compared to US$5.5 million as of December 31, 2021. Research and Development (R&D) Expenses: R&D expenses were US$45.1 million for the six months ended June 30, 2022, compared to US$31.5 million for the same period in 2021. The rise in R&D expenses was primarily due to increased R&D activities for the company’s clinical programs, as well as preclinical testing for candidates in the IND-enabling phase. Administrative Expenses:Administrative expenses were US$6.8 million for the six months ended June 30, 2022, compared to US$7.4 million for the same period in 2021. The decrease was primarily due to reduction in share-based compensation expenses. Net Loss:The net loss attributable to Adagene Inc.’s shareholders was US$47.6 million for the six months ended June 30, 2022, compared to US$37.2 million for the six months ended June 30, 2021. Ordinary Shares Outstanding:As of June 30, 2022, there were 54,278,981 ordinary shares issued and outstanding. Please note that each American depository share, or ADS, represents one and one quarter (1.25) ordinary shares of the company. 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 appliable, was US$41.9 million for the six months ended June 30, 2022, compared to US$27.0 million for the six months ended June 30, 2021. Please refer to the section in this press release titled “Reconciliation of GAAP and Non-GAAP Results” for details. 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 AdageneAdagene 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 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 KnoeflerAdagene650-739-9952ir@adagene.com FINANCIAL TABLES FOLLOW Unaudited Consolidated Balance Sheets December 31,2021 June 30,2022 US$ US$ASSETS Current assets: Cash and cash equivalents 174,391,243 168,035,499 Accounts receivable, net 3,000,000 — Amounts due from related parties 4,506,670 1,870,082 Prepayments and other current assets 4,055,921 5,107,271 Total current assets 185,953,834 175,012,852 Property, equipment and software, net 3,487,617 3,072,032 Operating lease right-of-use assets — 399,789 Other non-current assets 69,275 72,799 TOTAL ASSETS 189,510,726 178,557,472 LIABILITIES AND SHAREHOLDERS’ EQUITY Current liabilities: Accounts payable 3,321,615 4,665,872 Contract liabilities 5,500,000 20,176,826 Amounts due to related parties 10,466,061 17,508,933 Accruals and other current liabilities 4,379,243 4,237,621 Income tax payable 1,657,450 2,256,601 Short-term borrowings 3,121,226 5,960,008 Current portion of long-term borrowings 1,376,319 1,352,177 Current portion of operating lease liabilities — 297,066 Total current liabilities 29,821,914 56,455,104 Long-term borrowings 2,991,829 9,260,363 Operating lease liabilities — 128,083 Deferred tax liabilities 44,163 — Other non-current liabilities 94,107 29,800 TOTAL LIABILITIES 32,952,013 65,873,350 Commitments and contingencies Shareholders’ equity: Ordinary shares (par value of US$0.0001 per share; 640,000,000 shares authorized, and 54,595,667 shares issued and outstanding as of December 31, 2021; and 640,000,000 shares authorized, and 54,278,981 shares issued and outstanding as of June 30, 2022) 5,627 5,657 Treasury shares (94,074 shares as of December 31, 2021 and 1,234,834 shares as of June 30, 2022) (619,605) (3,666,957)Additional paid-in capital 336,099,931 342,631,313 Accumulated other comprehensive income (loss) (93,981) 190,167 Accumulated deficit (178,833,259) (226,476,058)Total shareholders’ equity 156,558,713 112,684,122 TOTAL LIABILITIES AND SHAREHOLDERS’ EQUITY 189,510,726 178,557,472 Unaudited Consolidated Statements of Comprehensive Loss For the Six MonthsEnded June 30, 2021 For the Six MonthsEnded June 30, 2022 US$ US$Revenues Licensing and collaboration revenue 1,358,836 3,923,174 Expenses Research and development expenses (31,462,546) (45,148,357)Administrative expenses (7,400,123) (6,848,925)Loss from operations (37,503,833) (48,074,108)Interest income 69,332 14,931 Interest expense (192,866) (211,434)Other income, net 822,837 430,671 Foreign exchange gain (loss), net (386,153) 756,085 Loss before income tax (37,190,683) (47,083,855)Income tax expense — (558,944)Net loss attributable to Adagene Inc.’s shareholders (37,190,683) (47,642,799)Other comprehensive income (loss) Foreign currency translation adjustments, net of nil tax 197,483 284,148 Total comprehensive loss attributable to Adagene Inc.’s shareholders (36,993,200) (47,358,651)Net loss attributable to Adagene Inc.’s shareholders (37,190,683) (47,642,799)Accretion of convertible redeemable preferred shares to redemption value (28,553) — Net loss attributable to ordinary shareholders (37,219,236) (47,642,799)Weighted average number of ordinary shares used in per share calculation: —Basic 45,514,701 54,533,161 —Diluted 45,514,701 54,533,161 Net loss per ordinary share —Basic (0.82) (0.87)—Diluted (0.82) (0.87) Reconciliation of GAAP and Non-GAAP Results For the Six MonthsEnded June 30, 2021 For the Six MonthsEnded June 30, 2022 US$ US$GAAP net loss attributable to ordinary shareholders (37,219,236) (47,642,799)Add back: Share-based compensation expenses 10,152,791 5,725,868 Accretion of convertible redeemable preferred shares to redemption value 28,553 — Non-GAAP net loss (27,037,892) (41,916,931)Weighted average number of ordinary shares used in per share calculation: —Basic 45,514,701 54,533,161 —Diluted 45,514,701 54,533,161 Non-GAAP net loss per ordinary share —Basic (0.59) (0.77)—Diluted (0.59) (0.77)

After a record year for biotech IPOs in 2020, forecasts were bullish on another strong year showing for public offerings — and 2021 hasn’t disappointed so far. Now, a clutch of four biotechs chasing rare disease and cancer and a New York SPAC are ready to join the party. Three more companies filed to head to Nasdaq on Tuesday, as well as a SPAC, with an additional Dutch biotech filing Friday. All in all, early days indicate another big year, at least to start, with 12 companies either pricing or filing their IPOs in the first 20 days of January. Biotech still has a long way to go to reach the chart-topping 81 IPOs recorded last year and $13.5 billion raised. But here are the newest companies helping get the industry off to a hot start. China’s Adagene looks to index new HERV-based CAR-T A little over a week after discovering a new CAR-T candidate, the Chinese biotech Adagene is shooting to go public. Adagene’s CAR-T for renal cell carcinoma is the first the biotech’s aware of to target a human endogenous retrovirus expressed in the majority of clear-cell kidney tumors. And on the back of more than $150 million in fundraising, including a $69 million Series D last January, Adagene is penciling in $125 million for their IPO raise. Adagene’s candidate was developed in tandem with the NHLBI in the lab of Richard Childs, chief of the Laboratory of Transplantation Immunotherapy. The NIH is expected to take over manufacturing and clinical development. Regardless of how much cash it ends up raising, Adagene said in its S-1 it plans to allocate 95% of funds to R&D. The company will direct 26% of funds toward its lead candidate, ADG106, a monoclonal antibody and CD137 agonist, which is currently in Phase Ib/IIa trials for advanced or metastatic solid tumors and/or relapsed/refractory non-Hodgkin’s lymphoma. Another 26% of funds are slated to go toward Adagene’s other two programs, ADG116 and ADG126. Both programs seek to block the known cancer target CTLA-4, with ADG116 focusing on a “unique” epitope. The former has started a Phase I in advanced metastatic solid tumors while the latter hasn’t yet hit the clinic. Bristol Myers Squibb, which pioneered the first and only CTLA-4 inhibitor Yervoy, also tried developing a 4-1BB agonist antibody dubbed urelumab, but hopes for a monotherapy were dashed after liver toxicities emerged. The last 43% allocated to R&D will help fund preclinical candidates and further platform development, Adagene said. — Max Gelman Pharvaris pencils in $100 million raise to back oral HAE approach A couple months after nabbing $80 million in venture cash, Netherlands-based Pharvaris has penciled in a $100 million jump onto Nasdaq to back its upstart approach for the rare genetic condition hereditary angioedema (HAE). Pharvaris’ lead program, an inhibitor and selective small-molecule bradykinin B2-receptor antagonist, is in development as an oral alternative to currently available HAE treatments — like CSL’s Haegarda and Takeda’s Cinryze, Takhzyro and Firazyr, which are all injectable. “We designed PHA121 to improve upon the therapeutic profile of existing therapies and, through oral delivery, to provide patients with quality of life and convenience that is superior to current standard-of-care HAE treatments, which are injectables,” the F-1 states. The biotech was founded by Berndt Modig, now CEO, and a cast of veterans from Jerini, the biotech that originally developed Firazyr. Back in November, the company released Phase I data from 16 healthy volunteers it said suggest their molecule is 24 times more potent than Firazyr. HAE is characterized by painful swelling in hands, feet and occasionally in the airways or intestinal walls. Attacks are unpredictable, and have multiple triggers. Patients experience a median of 14 attacks per year, and half experience potentially life-threatening airway attacks at least once in their lifetime, Pharvaris said, citing scientific publications. The company is launching two Phase II trials, one for prophylaxis and one for treating acute pain. If those are successful, they’ll follow up with pivotal Phase III studies. They plan on reading out Phase II data for the acute patients in 2022. Viking Global Investors and General Atlantic, which led the Series C, hold just over 6.03% of shares each, according to the F-1. Modig has a 5.27% stake. — Nicole DeFeudis On the heels of ASH, NexImmune guns for $86 million IPO raise NexImmune has maintained a relatively low profile after completing its $23 million Series A way back in 2018. But now the Gaithersburg, MD-based biotech has two programs in the clinic and plans to go public with an estimated $86 million raise. The company was spun out of Johns Hopkins and centers around the idea of specialized nanoparticles that act as antigen-presenting cells to incite a T cell attack on tumors. NexImmune’s ultimate goal is to provide a more durable attack involving more targets and less likelihood of a setback for patients, particularly if they can make an impact on naïve and memory T cells to keep the human immune system on alert. Within its S-1, NexImmune said the IPO funds will go toward its two lead programs, NEXI-001 and NEXI-002 that focus on donor-derived and patient-derived T cells, respectively. NEXI-001 is in an ongoing Phase I/II study in acute myeloid leukemia, with initial results presented last month at ASH. Among the two dozen or so patients, the candidate was shown to induce a return to baseline levels of absolute lymphocyte counts within 3 to 35 days. The program is still in its early clinical days, however. There haven’t been any readouts for NEXI-002 yet, but NexImmune dosed the first patient in a Phase I/II study in multiple myeloma last October. — Max Gelman Biophytis takes a second shot at a Nasdaq debut Second time’s the charm for Biophytis. The French biotech previously filed an F-1 back in May 2019, penciling in a $15 million hop onto Nasdaq. But it withdrew later that July due to “unfavorable market conditions.” Now, as the 2021 IPO queue begins to take shape, Biophytis is back — penciling in another $15 million raise for its Nasdaq debut. If successful this time around, Biophytis plans on funneling most of the IPO funds into its lead program: a small molecule dubbed Sarconeos, which the biotech believes can treat sarcopenia, Duchenne Muscular Dystrophy (DMD), and even SARS-CoV-2 pneumonia. Sarconeos is designed to activate the MAS receptor in muscle cells, a key component of the Renin-angiotensin system (RAS) — an endocrine system known to control things like fluid balance, blood pressure, cardiovascular function and smooth, cardiac and skeletal muscle metabolism. By activating the MAS receptor, Sarconeos triggers two downstream signaling pathways in myocytes that are impaired in muscle-wasting conditions, according to Biophytis. The initial target indication is sarcopenia, the age-related degeneration of skeletal muscle that leads to muscle mass strength, balance and the ability to stand or walk — and for which there’s no approved treatment or widely accepted standard of care, Biophytis said. The candidate is currently in a Phase II study for that indication, with topline results coming in Q2 this year. The oral drug is also in Phase II/III for Covid-19 patients with pneumonia, with the first interim analysis scheduled for Q1. If all goes well, Biophytis says it could file for emergency use with the FDA and EMA in Q2. “Most people infected with the COVID-19 virus will experience mild to moderate respiratory illness and recover without requiring special treatment,” the F-1 states. Biophytis is looking to help “older people, and those with underlying medical problems like cardiovascular disease, diabetes, chronic respiratory disease and cancer,” who are “more likely to develop serious illness.” The company also snagged IND approval for a Phase I/II trial in DMD last month, and hopes to launch a “seamless” clinical trial — one that combines multiple phases into an adaptive study — in the first half of 2021, according to the F-1. Stanislas Veillet, Biophytis’ co-founder and CEO who hails from Danone and Monsanto, owns 4% of the company’s stock. —Nicole DeFeudis CEO of small NYC biotech heads up $50 million SPAC A new SPAC has emerged, and it’s being led by the CEO of a small New York City biotech. The blank check company is called FoxWayne Enterprises Acquisition and seeks to reverse merge with a company following a $50 million raise. Robb Knie, CEO of Hoth Therapeutics, is leading the charge by offering 5 million shares at $10 apiece. FoxWayne originally filed its S-1 back in December and submitted its 8-A last week. The filings were accepted Tuesday. — Max Gelman