Adenocarcinoma of Esophagus

Recently announced agreement to divest assets and business operations in China marks an important milestone for the Company; the transaction is expected to close by the end of March 2024 Uliledlimab (CD73 antibody) on track to file an IND in combination with chemotherapy and checkpoint inhibitors for patients with newly diagnosed NSCLC in 1H 2024 First patient dosed in an ongoing, triplet combination, dose escalation study of givastomig (CLDN18.2x4-1BB bispecific antibody) in 1Q 2024 RMB2.3 billion (US$321.8 million) in cash and cash equivalents, and short-term investments as of December 31, 2023 ROCKVILLE, Md., March 14, 2024 /PRNewswire/ -- I-Mab (the "Company") (NASDAQ: IMAB), a U.S.-based, global biotech company, exclusively focused on the development and potential commercialization of highly differentiated immunotherapies for the treatment of cancer, today announced financial results for the full year ended December 31, 2023, and highlighted recent business updates. "2023 was a transitional year for I-Mab and we were pleased to report encouraging clinical results in our two lead global assets in oncology, uliledlimab and givastomig. As we prepare for the closing of the strategic divestiture, we look forward to providing investors with a road map to value creation and believe that our differentiated clinical assets, uliledlimab, givastomig, and ragistomig will achieve critical milestones and trial initiations this year," said Raj Kannan, Director and Chief Executive Officer of I-Mab. Pipeline Overview and Upcoming Milestones: Uliledlimab: Phase 2, with a focus on non-small cell lung cancer (NSCLC) Uliledlimab is designed to target CD73 and promote stronger activation of the patient's immune system against cancer cells. Uliledlimab is potentially differentiated from other products in development due to its non-competitive binding with adenosine monophosphate and the potential for complete inhibition of CD73's immune dampening function. Encouraging results from a Phase 2 study of uliledlimab in combination with toripalimab, presented at the American Society for Clinical Oncology (ASCO 2023) in patients with advanced NSCLC, provided compelling support for further development of uliledlimab. In particular, the subset of patients with both high CD73 expression and PD-L1 TPS>1% showed an impressive 63% overall response rate. Additionally, enrollment of patients with treatment resistant ovarian cancer has been completed, and ongoing efforts will be streamlined to focus on expediting NSCLC development. Upon the receipt of the investigational new drug (IND) approval, the Company plans to initiate the triplet study for uliledlimab in combination with chemotherapy and checkpoint inhibitors in newly diagnosed patients with advanced NSCLC in the second half of 2024. Givastomig (Claudin 18.2 x 4-1BB bispecific antibody): Phase 1b, with a focus on gastric cancer and esophageal adenocarcinoma Givastomig was designed as a bispecific antibody to target Claudin 18.2-positive tumor cells, with conditional activation of pro-immune 4-1BB in the tumor microenvironment. Phase 1 monotherapy data presented at the European Society of Medical Oncology (ESMO 2023) showed encouraging objective responses in patients with gastric cancer and esophageal adenocarcinoma whose tumors progressed or recurred after prior standard treatments, including those with low levels of Claudin 18.2 expression. This program is being jointly developed with ABL Bio. I-Mab owns 50% of the global rights of givastomig. The enrollment of patients from the U.S. and China with newly diagnosed (frontline treatment) gastric and esophageal cancer in combination with chemotherapy and a checkpoint inhibitor began in the first quarter of 2024. Ragistomig (PD-L1 x 4-1BB bispecific antibody): Phase 1 dose escalation, with a focus on solid tumors Ragistomig was designed as a bispecific antibody to address PD-L1 resistant tumors, differentiated by the conditional activation of 4-1BB's pro-immune stimulation when it binds to its PD-L1 target. Early observations reported by our development partner, ABL Bio, showed promising objective responses in patients with various solid tumors whose tumors progressed or recurred after prior standard treatments, including in patients with relapsed or refractory cancer after prior PD-L1 inhibitors. These early signs of efficacy are encouraging, and enrollment in the Phase 1 study continues. This program is being jointly developed with ABL Bio. I-Mab owns 50% of the global rights of ragistomig (TJ-L14B/ABL503). Top-line Phase 1 dose escalation and dose expansion results are expected to be presented at a major medical conference in the first half of 2024. Impact of Strategic Transaction on Pipeline The agreement to divest assets and business operations in China, previously announced in a press release on February 7, 2024, is expected to be completed by the end of March 2024. Upon the closing of the transaction, the Greater China rights for assets including eftansomatropin alfa, felzartamab, uliledlimab, and givastomig will be transferred to I-Mab Biopharma (Hangzhou) Co., Ltd., an unconsolidated affiliate (the " Hangzhou Company"). I-Mab will no longer bear future development costs of these divested assets in China and may receive an aggregate consideration of the RMB equivalent of up to US$80 million, contingent on the Hangzhou Company group's achievement of certain future regulatory and sales-based milestone events relating to these divested assets in China. The transaction, if closed, will also extinguish existing repurchase obligations owed by a wholly-owned subsidiary of the Company in the amount of approximately US$183 million. As a result of the closing of the transaction, the Company will cease consolidation of the divested entities, assets, and businesses as well as their corresponding financial results. The Company's financial condition and results of operations will be materially affected and the Company's historical results will not be indicative of future financial condition or results of operations. Full-Year 2023 Financial Results Cash Position As of December 31, 2023, the Company had cash, cash equivalents, and short-term investments of RMB2.3 billion (US$321.8 million), compared with RMB3.5 billion as of December 31, 2022. Share Buyback In August 2023, the Board of Directors of the Company authorized a new share repurchase program under which the Company may repurchase up to US$40 million of American Depository Shares ("ADSs"), each ten ADSs representing 23 ordinary shares of the Company, or ordinary shares in aggregate over a 12-month period. During the period ended December 31, 2023, the Company repurchased US$8.6 million of its ADSs, equating to 4,633,386 ADSs or 10,656,794 ordinary shares. As of December 31, 2023, the Company had issued and outstanding ordinary shares of 185,613,662, representing the equivalent of 80,701,592 ADSs assuming the conversion of all ordinary shares into ADSs. Net Revenues Total net revenues for the full year of 2023 were RMB27.6 million (US$3.9 million), compared with RMB-221.6 million (US$-32.1 million) for the full year of 2022. Total net revenues in 2023 consisted of revenues recognized in connection with the strategic collaboration with AbbVie Inc. (AbbVie) and revenues generated from the supply of investigational products to AbbVie and Human Immunology Biosciences, Inc. The negative figure for net revenue in 2022 was primarily due to a one-time, non-cash accounting treatment of US$-48.0 million (equivalent to RMB-314.2 million) recorded in the second half of 2022 following the amendment to the original license and collaboration agreement with AbbVie in August 2022. This amendment led to a reduced probability of achieving a key milestone that was included in the consideration of revenue recognition in prior years. Research & Development Expenses Research and development expenses for the full year of 2023 were RMB810.6 million (US$114.2 million), compared with RMB904.9 million (US$131.2 million) for the full year of 2022. The decrease was primarily due to reduced payroll expenses related to headcount optimization as a result of asset prioritization and reduced share-based compensation expenses. Share-based compensation expense was RMB66.8 million (US$9.4 million) for the full year of 2023, compared with RMB117.9 million (US$17.1 million) for the full year of 2022. Administrative Expenses Administrative expenses for the full year of 2023 were RMB453.0 million (US$63.8 million), compared with RMB815.8 million (US$118.3 million) for the full year of 2022. The decrease was primarily due to reduced payroll expenses related to decreased headcount as a result of resource optimization and reduced share-based compensation expenses for management personnel, reduced expenses for professional services, and reduced legal expenses in relation to the disputes with Tracon Pharmaceuticals, Inc. of RMB95.5 million (US$13.5 million). Share-based compensation expense was RMB126.2 million (US$17.8 million) for the full year of 2023, compared with RMB239.3 million (US$34.7 million) for the full year of 2022. Other Expenses, Net Net other expenses for the full year of 2023 were RMB38.1 million (US$5.4 million), compared with RMB126.6 million (US$18.4 million) for the full year of 2022. The change was primarily driven by unrealized exchange rate losses due to the significant fluctuation in the exchange rate of the Renminbi against the U.S. dollar in 2022. Equity in Loss of Affiliates Equity in loss of affiliates for the full year of 2023 was RMB80.0 million (US$11.3 million), compared with RMB437.5 million (US$63.4 million) for the full year of 2022. The loss was mainly recognized in relation to the operating loss of the Company's investee, I-Mab Biopharma (Hangzhou) Co., Ltd. Impairment of Goodwill For the full year of 2023, the Company recognized an impairment of goodwill of RMB162.6 million (US$22.9 million). The goodwill impairment resulted from the Company's annual impairment analysis, and reflects the continued disconnect between I-Mab's anticipated future performance and present uncertainty reflected in its market valuation. Net Loss Net loss for the full year of 2023 was RMB1,465.7 million (US$206.4 million), compared with RMB2,507.3 million (US$363.5 million) for the year 2022. Net loss per share attributable to ordinary shareholders for the full year of 2023 was RMB7.19 (US$1.01), compared with RMB13.21 (US$1.92) for the full year of 2022. Net loss per ADS attributable to ordinary shareholders for the full year of 2023 was RMB16.54 (US$2.33), compared with RMB30.38 (US$4.41) for the full year of 2022. Non-GAAP Net Loss Non-GAAP adjusted net loss, which excludes share-based compensation expenses and impairment of goodwill, for the full year of 2023 was RMB1,105.3 million (US$155.7 million), compared with RMB2,136.3 million (US$309.7 million) for the full year of 2022. Non-GAAP adjusted net loss per share attributable to ordinary shareholders for the full year of 2023 was RMB5.42 (US$0.76), compared with RMB11.26 (US$1.63) for the full year of 2022. Non-GAAP adjusted net loss per ADS attributable to ordinary shareholders for the full year of 2023 was RMB12.47 (US$1.76), compared with RMB25.90 (US$3.75) for the full year of 2022. Use of Non-GAAP Financial Measures To supplement its consolidated financial statements, which are presented in accordance with U.S. GAAP, the Company uses adjusted net income (loss) as a non-GAAP financial measure. Adjusted net income (loss) represents net income (loss) before share-based compensation and impairment of goodwill. The Company's management believes that adjusted net income (loss) facilitates understanding of operating results and provides management with a better capability to plan and forecast future periods. For more information on the non-GAAP financial measures, please see the table captioned "Reconciliation of GAAP and Non-GAAP Results" set forth at the end of this press release. Non-GAAP information is not prepared in accordance with GAAP and may be different from non-GAAP methods of accounting and reporting used by other companies. The presentation of this additional information should not be considered a substitute for GAAP results. A limitation of using adjusted net income (loss) is that adjusted net income (loss) excludes share-based compensation expense and impairment of goodwill that has been and may continue to be incurred in the future. Exchange Rate Information This announcement contains translations of certain Renminbi amounts into U.S. dollars at a specified rate solely for the convenience of the reader. Unless otherwise noted, all translations from Renminbi to U.S. dollars of the financial results for the year of 2023 are made at a rate of RMB7.0999 to US$1.00, the rate in effect as of December 29, 2023, published by the Federal Reserve Board. All translations from Renminbi to U.S. dollars of the financial results for the year of 2022 are made at a rate of RMB6.8972 to US$1.00, the rate in effect as of December 30, 2022 published by the Federal Reserve Board. Notes: (1) Includes share-based compensation expense of RMB117,876 thousand (US$17,090 thousand) and RMB66,758 thousand (US$9,403 thousand) for the years ended December 31, 2022 and 2023, respectively. (2) Includes share-based compensation expense of RMB239,272 thousand (US$34,691 thousand) and RMB126,244 thousand (US$17,781 thousand) for the years ended December 31, 2022 and 2023, respectively. (3) Includes share-based compensation expense of RMB13,852 (US$2,008 thousand) and RMB4,815 thousand (US$678 thousand) for the years ended December 31, 2022 and 2023, respectively. (4) Each ten ADSs represents twenty-three ordinary shares. About I-Mab I-Mab (NASDAQ: IMAB) is a U.S.-based, global biotech company, exclusively focused on the development and potential commercialization of highly differentiated immunotherapies for the treatment of cancer. I-Mab has established operations in the U.S. in Rockville, Maryland, and in San Diego, California. For more information, please visit and follow us on LinkedIn, X, and WeChat. I-Mab Forward Looking Statements This announcement contains forward-looking statements. These statements are made under the "safe harbor" provisions of the U.S. Private Securities Litigation Reform Act of 1995. These forward-looking statements can be identified by terminology such as "will", "expects", "believes", "designed to", "anticipates", "future", "intends", "plans", "potential", "estimates", "confident", and similar terms or the negative thereof. I-Mab may also make written or oral forward-looking statements in its periodic reports to the U.S. Securities and Exchange Commission (the "SEC"), in its annual report to shareholders, in press releases and other written materials and in oral statements made by its officers, directors or employees to third parties. Statements that are not historical facts, including statements about I-Mab's beliefs and expectations, are forward-looking statements. Forward-looking statements in this press release include, without limitation, statements regarding: the timing of the completion of the expected divestiture of the Company's assets and business operations in China and its anticipated impact on the Company (including the transfer of Greater China rights for assets, including eftansomatropin alfa, felzartamab, uliledlimab, and givastomig to the Hangzhou Company, the expected consideration to be received by I-Mab and the expected extinguishment of an existing repurchase obligation of US$183 million); the Company's expectations regarding providing a road map to value creation and its belief that its clinical oncology programs will achieve critical milestones and trial initiations this year; the Company's pipeline overview and upcoming anticipated milestones, including with respect to uliledlimab, givastomig, and ragistomig, and the intended impact and the Company's plans with respect thereto. Forward-looking statements involve inherent risks and uncertainties that may cause actual results to differ materially from those contained in these forward-looking statements, including but not limited to the following: I-Mab's ability to demonstrate the safety and efficacy of its drug candidates; the clinical results for its drug candidates, which may or may not support further development or New Drug Application/Biologics License Application (NDA/BLA) approval; the content and timing of decisions made by the relevant regulatory authorities regarding regulatory approval of I-Mab's drug candidates; I-Mab's ability to achieve commercial success for its drug candidates, if approved; I-Mab's ability to obtain and maintain protection of intellectual property for its technology and drugs; I-Mab's reliance on third parties to conduct drug development, manufacturing and other services; and I-Mab's limited operating history and I-Mab's ability to obtain additional funding for operations and to complete the development and commercialization of its drug candidates, as well as those risks more fully discussed in the "Risk Factors" section in I-Mab's most recent annual report on Form 20-F, as well as discussions of potential risks, uncertainties, and other important factors in I-Mab's subsequent filings with the SEC. All forward-looking statements are based on information currently available to I-Mab. I-Mab 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. For more information, please contact: I-Mab Contacts SOURCE I-Mab

Results from the global, Phase 3 RATIONALE 302 trial showed TEVIMBRA prolonged the survival of patients who received prior systemic treatment compared to chemotherapy Approval represents the first indication in the U.S. for TEVIMBRA BASEL, Switzerland & BEIJING & CAMBRIDGE, Mass.--(BUSINESS WIRE)-- BeiGene Ltd. (NASDAQ: BGNE; HKEX: 06160; SSE: 688235), a global oncology company, today announced that the U.S. Food and Drug Administration (FDA) has approved TEVIMBRA® (tislelizumab-jsgr) as monotherapy for the treatment of adult patients with unresectable or metastatic esophageal squamous cell carcinoma (ESCC) after prior systemic chemotherapy that did not include a PD-(L)1 inhibitor. TEVIMBRA will be available in the U.S. in the second half of 2024. “Today’s FDA approval of TEVIMBRA for patients with ESCC who have previously received chemotherapy, along with its ongoing review of our BLA for first-line ESCC patients, represents a significant step in our commitment to bringing this therapy to more patients around the world,” said Mark Lanasa, M.D., Ph.D., Chief Medical Officer, Solid Tumors at BeiGene. “As BeiGene’s first drug candidate produced through our immuno-oncology program and second approved medicine in the U.S., TEVIMBRA is poised to be a critical pillar of our solid tumor development program, which spans more than 17 registration-enabling clinical trials in more than 30 countries across regions globally.” The approval is based on the RATIONALE 302 trial, which met its primary endpoint in the intention-to-treat (ITT) population with a statistically significant and clinically meaningful survival benefit for TEVIMBRA compared with chemotherapy. In the ITT population, the median overall survival (OS) in the TEVIMBRA arm was 8.6 months (95% CI: 7.5, 10.4) compared to 6.3 months (95% CI: 5.3, 7.0) in the chemotherapy arm (p=0.0001; hazard ratio [HR]=0.70 [95% CI: 0.57, 0.85]). The safety pro TEVIMBRA was favorable over chemotherapy.i The most common (≥20%) adverse reactions for TEVIMBRA, including laboratory abnormalities, were increased glucose, decreased hemoglobin, decreased lymphocytes, decreased sodium, decreased albumin, increased alkaline phosphatase, anemia, fatigue, increased AST, musculoskeletal pain, decreased weight, increased ALT and cough.i “Patients diagnosed with advanced or metastasized ESCC, the most common histologic subtype of esophageal cancer, often progress following initial therapy and are in need of new options,” Syma Iqbal, M.D., Associate Professor of Clinical Medicine, Section Chief Gastrointestinal Oncology, Division of Medical Oncology and Cancer Physician in Chief, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California. “The RATIONALE 302 trial showed that patients with previously treated ESCC who received TEVIMBRA saw a clinically meaningful survival benefit, highlighting its potential as an important treatment option for these patients.” Tislelizumab received approval by the European Commission for advanced or metastatic ESCC after prior chemotherapy in 2023 and a positive opinion by the Committee for Medicinal Products for Human Use of the European Medicines Agency (EMA) in February 2024 as a treatment for non-small cell lung cancer across three indications. The FDA is also reviewing Biologics License Applications (BLAs) for tislelizumab as a first-line treatment for patients with unresectable, recurrent, locally advanced, or metastatic ESCC and patients with locally advanced unresectable or metastatic gastric or gastroesophageal junction (G/GEJ) adenocarcinoma. The target action dates are July and December 2024, respectively. BeiGene has launched more than 17 potentially registration-enabling trials with TEVIMBRA, of which 11 Phase 3 randomized trials and four Phase 2 trials have already had positive readouts. Through these trials, TEVIMBRA has demonstrated its potential to deliver clinically meaningful improvements in survival benefits and quality of life for hundreds of thousands of cancer patients across a range of tumor types – in many cases, regardless of PD-(L)1 status – both as monotherapy and in combination with other regimens. More than 900,000 patients have been prescribed TEVIMBRA globally to date. About RATIONALE 302 RATIONALE 302 is a global, randomized, open-label, Phase 3 study (NCT03430843) designed to investigate the efficacy and safety of TEVIMBRA when compared with investigator’s choice of chemotherapy as a second-line treatment for patients with unresectable, locally advanced or metastatic ESCC. The study randomized 512 patients from 132 research sites in 11 countries in Europe, Asia and North America. About ESCC Globally, esophageal cancer (EC) is the sixth most common cause of cancer-related deaths, and ESCC is the most common histologic subtype, accounting for nearly 90% of ECs.ii An estimated 957,000 new EC cases are projected in 2040, an increase of nearly 60% from 2020, underscoring the need for additional effective treatments.ii EC is a rapidly fatal disease, and more than two-thirds of patients have advanced or metastatic disease at the time of diagnosis, with an expected five-year survival rate of less than 6% for those with distant metastases.iii About TEVIMBRA® (tislelizumab-jsgr) Tislelizumab is a uniquely designed humanized immunoglobulin G4 (IgG4) anti-programmed cell death protein 1 (PD-1) monoclonal antibody with high affinity and binding specificity against PD-1. It is designed to minimize binding to Fc-gamma (Fcγ) receptors on macrophages, helping to aid the body’s immune cells to detect and fight tumors. U.S. Indication and Important Safety Information for TEVIMBRA (tislelizumab-jsgr) INDICATION TEVIMBRA (tislelizumab-jsgr), as a single agent, is indicated for the treatment of adult patients with unresectable or metastatic esophageal squamous cell carcinoma after prior systemic chemotherapy that did not include a PD-(L)1 inhibitor. WARNINGS AND PRECAUTIONS Severe and Fatal Immune-Mediated Adverse Reactions TEVIMBRA is a monoclonal antibody that belongs to a class of drugs that bind to either the programmed death receptor-1 (PD-1) or PD-ligand 1 (PD-L1), blocking the PD-1/PD-L1 pathway, thereby removing inhibition of the immune response, potentially breaking peripheral tolerance and inducing immune-mediated adverse reactions. Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue. Immune-mediated adverse reactions can occur at any time after starting treatment with a PD-1/PD-L1 blocking antibody. While immune-mediated adverse reactions usually manifest during treatment with PD-1/PD-L1 blocking antibodies, immune-mediated adverse reactions can also manifest after discontinuation of PD-1/PD-L1 blocking antibodies. Important immune-mediated adverse reactions listed here may not include all possible severe and fatal immune-mediated reactions. Early identification and management of immune-mediated adverse reactions are essential to ensure safe use of PD-1/PD-L1 blocking antibodies. Monitor patients closely for symptoms and signs that may be clinical manifestations of underlying immune-mediated adverse reactions. Evaluate liver enzymes, creatinine, and thyroid function at baseline and periodically during treatment. In cases of suspected immune-mediated adverse reactions, initiate appropriate workup to exclude alternative etiologies, including infection. Institute medical management promptly, including specialty consultation as appropriate. Withhold or permanently discontinue TEVIMBRA depending on severity. In general, if TEVIMBRA requires interruption or discontinuation, administer systemic corticosteroid therapy (1 to 2 mg/kg/day prednisone or equivalent) until improvement to Grade 1 or less. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Consider administration of other systemic immunosuppressants in patients whose immune-mediated adverse reactions are not controlled with corticosteroids. Immune-Mediated Pneumonitis TEVIMBRA can cause immune-mediated pneumonitis, which can be fatal. In patients treated with other PD-1/PD-L1 blocking antibodies, the incidence of pneumonitis is higher in patients who have received prior thoracic radiation. Immune-mediated pneumonitis occurred in 3.8% (75/1972) of patients receiving TEVIMBRA, including fatal (0.2%), Grade 4 (0.3%), Grade 3 (1.4%), and Grade 2 (1.7%) adverse reactions. Pneumonitis led to permanent discontinuation of TEVIMBRA in 35 (1.8%) patients and withholding of TEVIMBRA in 27 (1.4%) patients. Systemic corticosteroids were required in all patients with pneumonitis. Immune-mediated pneumonitis resolved in 47% of the 75 patients. Of the 27 patients in whom TEVIMBRA was withheld for pneumonitis, 18 reinitiated TEVIMBRA after symptom improvement; of these, 3 (17%) patients had recurrence of pneumonitis. Immune-Mediated Colitis TEVIMBRA can cause immune-mediated colitis, which can be fatal. Cytomegalovirus (CMV) infection/reactivation has been reported in patients with corticosteroid-refractory immune-mediated colitis treated with PD-1/PD-L1 blocking antibodies. In cases of corticosteroid-refractory colitis, consider repeating infectious workup to exclude alternative etiologies. Immune-mediated colitis occurred in 0.9% (17/1972) of patients receiving TEVIMBRA, including Grade 3 (0.4%), and Grade 2 (0.5%) adverse reactions. Colitis led to permanent discontinuation of TEVIMBRA in 2 (0.1%) patients and withholding of TEVIMBRA in 10 (0.5%) patients. All 17 patients received systemic corticosteroids. Twelve (71%) of the 17 patients received high-dose systemic corticosteroids. Two (12%) of the 17 patients received immunosuppressive treatment. Immune-mediated colitis resolved in 88% of the 17 patients. Of the 10 patients in whom TEVIMBRA was withheld for colitis, 8 reinitiated TEVIMBRA after symptom improvement; of these, 1 (13%) patient had recurrence of colitis. Immune-Mediated Hepatitis TEVIMBRA can cause immune-mediated hepatitis, which can be fatal. Immune-mediated hepatitis occurred in 1.7% (34/1972) of patients receiving TEVIMBRA, including fatal (0.1%), Grade 4 (0.1%), Grade 3 (1%), and Grade 2 (0.6%) adverse reactions. Immune-mediated hepatitis led to permanent discontinuation in 9 (0.5%) patients and withholding of TEVIMBRA in 20 (1%) patients. All patients received systemic corticosteroids. Twenty-nine (85%) of the 34 patients received high-dose systemic corticosteroids. One patient (2.9%) of the 34 patients received immunosuppressive treatment. Immune-mediated hepatitis resolved in 59% of the 34 patients. Of the 20 patients in whom TEVIMBRA was withheld for hepatitis, 12 reinitiated TEVIMBRA after symptom improvement; of these, 2 (17%) patients had recurrence of hepatitis. Immune-Mediated Endocrinopathies Adrenal Insufficiency TEVIMBRA can cause immune-mediated adrenal insufficiency. For Grade 2 or higher adrenal insufficiency, initiate symptomatic treatment, including hormone replacement as clinically indicated. Withhold TEVIMBRA depending on severity. Immune-mediated adrenal insufficiency occurred in 0.3% (6/1972) of patients receiving TEVIMBRA, including Grade 4 (0.1%), Grade 3 (0.1%), and Grade 2 (0.2%) adverse reactions. Adrenal insufficiency did not lead to permanent discontinuation of TEVIMBRA. TEVIMBRA was withheld in 5 out of the 6 patients. All 6 patients received systemic corticosteroids. Two (33%) of the 6 patients received high-dose systemic corticosteroids. Adrenal insufficiency resolved in 17% of the 6 patients. Hypophysitis TEVIMBRA can cause immune-mediated hypophysitis. Hypophysitis can present with acute symptoms associated with mass effect such as headache, photophobia, or visual field defects. Hypophysitis can cause hypopituitarism. Initiate hormone replacement as clinically indicated. Withhold or permanently discontinue TEVIMBRA depending on severity. Hypophysitis/hypopituitarism occurred in 0.1% (1/1972) of patients receiving TEVIMBRA, including a Grade 2 (0.1%) adverse reaction. No TEVIMBRA treatment discontinuation or withholding was required. Thyroid Disorders TEVIMBRA can cause immune-mediated thyroid disorders. Thyroiditis can present with or without endocrinopathy. Hypothyroidism can follow hyperthyroidism. Initiate hormone replacement for hypothyroidism or institute medical management of hyperthyroidism as clinically indicated. Withhold or permanently discontinue TEVIMBRA depending on severity. Thyroiditis: Immune-mediated thyroiditis occurred in 0.4% (7/1972) of patients receiving TEVIMBRA, including Grade 2 (0.3%) adverse reactions. Thyroiditis did not lead to permanent discontinuation of TEVIMBRA. TEVIMBRA was withheld in 1 (0.1%) patient. One (14%) of the 7 patients received systemic corticosteroids. Thyroiditis resolved in 29% of the 7 patients. Hyperthyroidism: Immune-mediated hyperthyroidism occurred in 0.6% (12/1972) of patients receiving TEVIMBRA, including Grade 3 (0.1%), and Grade 2 (0.5%) adverse reactions. Hyperthyroidism led to the permanent discontinuation of TEVIMBRA in 1 (0.1%) patient and withholding of TEVIMBRA in 1 (0.1%) patient. One (8%) of the 12 patients received systemic corticosteroids. Hyperthyroidism resolved in 92% of the 12 patients. Hypothyroidism: Immune-mediated hypothyroidism occurred in 7% (132/1972) of patients receiving TEVIMBRA, including Grade 4 (0.1%) and Grade 2 (5%) adverse reactions. TEVIMBRA was not permanently discontinued in any patient, while treatment was withheld in 6 (0.3%) patients. Two (1.5%) of the 132 patients received systemic corticosteroids. All 132 patients received hormone replacement therapy. Hypothyroidism resolved in 27% of the 132 patients. The majority (86%) of patients with hypothyroidism required long-term thyroid hormone replacement. Type 1 Diabetes Mellitus, which can present with Diabetic Ketoacidosis Type 1 diabetes mellitus has been reported with PD-1/PD-L1 blocking antibodies. Monitor patients for hyperglycemia or other signs and symptoms of diabetes. Initiate treatment with insulin as clinically indicated. Withhold or permanently discontinue TEVIMBRA depending on severity. Immune-Mediated Nephritis with Renal Dysfunction TEVIMBRA can cause immune-mediated nephritis, which can be fatal. Immune-mediated nephritis with renal dysfunction occurred in 0.4% (7/1972) of patients receiving TEVIMBRA, including Grade 4 (0.1%), Grade 3 (0.1%), and Grade 2 (0.2%) adverse reactions. TEVIMBRA was permanently discontinued in 3 (0.2%) patients and treatment was withheld in 3 (0.2%) patients. All patients received systemic corticosteroids. Nephritis with renal dysfunction resolved in 57% of the 7 patients. Of the 3 patients in whom TEVIMBRA was withheld for nephritis, 2 reinitiated TEVIMBRA after symptom improvement and one patient had recurrence of nephritis. Immune-Mediated Dermatologic Adverse Reactions TEVIMBRA can cause immune-mediated rash or dermatitis. Cases of severe cutaneous adverse reactions (SCARs), including exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis (TEN), have been reported, some with fatal outcome. Topical emollients and/or topical corticosteroids may be adequate to treat mild to moderate non-exfoliative rashes. Withhold or permanently discontinue TEVIMBRA depending on severity. Immune-mediated dermatologic adverse reactions occurred in 1.2% (24/1972) of patients receiving TEVIMBRA, including Grade 4 (0.2%), Grade 3 (0.4%), and Grade 2 (0.4%) adverse reactions. Dermatologic adverse reactions led to permanent discontinuation of TEVIMBRA in 3 (0.2%) patients and withholding of TEVIMBRA in 9 (0.5%) patients. Twenty-three (96%) of the 24 patients received systemic corticosteroids. Immune-mediated skin reactions resolved in 58% of the 24 patients. Of the 9 patients in whom TEVIMBRA was withheld for dermatologic adverse reactions, 8 reinitiated TEVIMBRA after symptom improvement; of these, 2 (25%) patients had recurrence of immune-mediated rash. Other Immune-Mediated Adverse Reactions The following clinically significant immune-mediated adverse reactions occurred at an incidence of less than 1% each in 1972 patients who received TEVIMBRA: myositis, myocarditis, arthritis, polymyalgia rheumatica, and pericarditis. The following additional clinically significant immune-mediated adverse reactions have been reported with other PD-1/PD-L1 blocking antibodies, including severe or fatal cases. Cardiac/Vascular: Vasculitis Nervous System: Meningitis, encephalitis, myelitis and demyelination, myasthenic syndrome/myasthenia gravis (including exacerbation), Guillain-Barre syndrome, nerve paresis, autoimmune neuropathy. Ocular: Uveitis, iritis, and other ocular inflammatory toxicities can occur. Some cases can be associated with retinal detachment. Various grades of visual impairment, including blindness, can occur. If uveitis occurs in combination with other immune-mediated adverse reactions, consider a Vogt-Koyanagi-Harada-like syndrome, as this may require treatment with systemic steroids to reduce the risk of permanent vision loss.­­ Gastrointestinal: Pancreatitis including increases in serum amylase and lipase levels, gastritis, duodenitis Musculoskeletal and Connective Tissue: Polymyositis, rhabdomyolysis and associated sequelae including renal failure Endocrine: Hypoparathyroidism Other (Hematologic/Immune): Hemolytic anemia, aplastic anemia, hemophagocytic lymphohistiocytosis, systemic inflammatory response syndrome, histiocytic necrotizing lymphadenitis (Kikuchi lymphadenitis), sarcoidosis, immune thrombocytopenic purpura, solid organ transplant rejection, other transplant (including corneal graft) rejection. Infusion-Related Reactions TEVIMBRA can cause severe or life-threatening infusion-related reactions. Infusion-related reactions occurred in 4.2% (83/1972) patients receiving TEVIMBRA, including Grade 3 or higher (0.3%) reactions. Monitor patients for signs and symptoms of infusion-related reactions. Slow the rate of infusion for mild (Grade 1) and interrupt the infusion for moderate (Grade 2) infusion-related reactions. For severe (Grade 3) or life-threatening (Grade 4) infusion-related reactions, stop infusion and permanently discontinue TEVIMBRA. Complications of Allogeneic HSCT Fatal and other serious complications can occur in patients who receive allogeneic hematopoietic stem cell transplantation (HSCT) before or after being treated with a PD-1/PD-L1 blocking antibody. Transplant-related complications include hyperacute graft-versus-host disease (GVHD), acute GVHD, chronic GVHD, hepatic veno-occlusive disease after reduced intensity conditioning, and steroid-requiring febrile syndrome (without an identified infectious cause). These complications may occur despite intervening therapy between PD-1/PD-L1 blockade and allogeneic HSCT. Follow patients closely for evidence of transplant-related complications and intervene promptly. Consider the benefit versus risks of treatment with a PD-1/PD-L1 blocking antibody prior to or after an allogeneic HSCT. Embryo-Fetal Toxicity Based on its mechanism of action, TEVIMBRA can cause fetal harm when administered to a pregnant woman. Animal studies have demonstrated that inhibition of the PD-1/PD-L1 pathway can lead to increased risk of immune-mediated rejection of the developing fetus resulting in fetal death. Advise women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with TEVIMBRA and for 4 months after the last dose. ADVERSE REACTIONS Permanent discontinuation of TEVIMBRA due to an adverse reaction occurred in 19% of patients. Adverse reactions which resulted in permanent discontinuation in ≥ 1% of patients were hemorrhage, pneumonitis (including pneumonitis and immune-mediated pneumonitis), and pneumonia. Dosage interruptions of TEVIMBRA due to an adverse reaction occurred in 23% of patients. Adverse reactions which required dosage interruptions in ≥ 2% of patients were pneumonia, pneumonitis, and fatigue. The most common (≥ 20%) adverse reactions, including laboratory abnormalities, were increased glucose, decreased hemoglobin, decreased lymphocytes, decreased sodium, decreased albumin, increased alkaline phosphatase, anemia, fatigue, increased AST, musculoskeletal pain, decreased weight, increased ALT, and cough. Please see full U.S. Prescribing Information including Medication Guide. About BeiGene BeiGene is a global oncology company that is discovering and developing innovative treatments that are more affordable and accessible to cancer patients worldwide. With a broad portfolio, we are expediting development of our diverse pipeline of novel therapeutics through our internal capabilities and collaborations. We are committed to radically improving access to medicines for far more patients who need them. Our growing global team of more than 10,000 colleagues spans five continents, with administrative offices in Basel, Beijing, and Cambridge, U.S. To learn more about BeiGene, please visit and follow us on LinkedIn and X (formerly known as Twitter). Forward-Looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 and other federal securities laws, including statements regarding BeiGene’s ability to bring TEVIMBRA to more patients around the world; the future significance of TEVIMBRA in BeiGene’s solid tumor development program; the potential of TEVIMBRA to be an important treatment for ESCC; and BeiGene’s plans, commitments, aspirations, and goals under the heading “About BeiGene.” Actual results may differ materially from those indicated in the forward-looking statements as a result of various important factors, including BeiGene's ability to demonstrate the efficacy and safety of its drug candidates; the clinical results for its drug candidates, which may not support further development or marketing approval; actions of regulatory agencies, which may affect the initiation, timing, and progress of clinical trials and marketing approval; BeiGene's ability to achieve commercial success for its marketed medicines and drug candidates, if approved; BeiGene's ability to obtain and maintain protection of intellectual property for its medicines and technology; BeiGene's reliance on third parties to conduct drug development, manufacturing, commercialization, and other services; BeiGene’s limited experience in obtaining regulatory approvals and commercializing pharmaceutical products and its ability to obtain additional funding for operations and to complete the development of its drug candidates and achieve and maintain profitability; and those risks more fully discussed in the section entitled “Risk Factors” in BeiGene’s most recent quarterly report on Form 10-Q, as well as discussions of potential risks, uncertainties, and other important factors in BeiGene's subsequent filings with the U.S. Securities and Exchange Commission. All information in this press release is as of the date of this press release, and BeiGene undertakes no duty to update such information unless required by law. To access BeiGene media resources, please visit our News & Media site. ___________________________ i Shen, L., Kato, K., Kim, S. B., Ajani, J. A., Zhao, K., He, Z., ... & Van Cutsem, E. (2022). Tislelizumab versus chemotherapy as second-line treatment for advanced or metastatic esophageal squamous cell carcinoma (RATIONALE-302): A randomized phase III study. Journal of Clinical Oncology. 40(26), 3065-3076. DOI: 10.1200/JCO.21.01926 ii Morgan E, et al. The Global Landscape of Esophageal Squamous Cell Carcinoma and Esophageal Adenocarcinoma Incidence and Mortality in 2020 and Projections to 2040: New Estimates From GLOBOCAN 2020. Gastroenterology. 2022 Sep;163(3):649-658.e2. doi: 10.1053/j.gastro.2022.05.054. Epub 2022 Jun 4. PMID: 35671803. iii National Cancer Institute. Cancer stat facts: esophageal cancer. .

Full-year 2023 revenue of $220 million, an increase of 60% compared to 2022 and above previously reported guidance Delivered 70,429 total test reports in 2023, an increase of 59% compared to 2022 Year-end 2023 cash, cash equivalents and marketable investment securities of $243 million Two critical peer-reviewed publications in 2023 demonstrating an association with DecisionDx®-Melanoma testing and improved patient outcomes Conference call and webcast today at 4:30 p.m. ET FRIENDSWOOD, Texas--(BUSINESS WIRE)-- Castle Biosciences, Inc. (Nasdaq: CSTL), a company improving health through innovative tests that guide patient care, today announced its financial results for the fourth quarter and year ended Dec. 31, 2023. “2023 was another exceptional year, with strong top-line growth and test report volume growth, driven in large part by consistent execution by the entire Castle team,” said Derek Maetzold, president and chief executive officer of Castle Biosciences. “I am extremely pleased with the continued success we saw from careful investments in our initiatives. We expanded our body of evidence, with data further demonstrating the potential of our tests to improve patient outcomes, including increased survival. In addition, our foundational dermatology business continued to expand solidly, and growth in our TissueCypher® Barrett’s Esophagus test outpaced our expectations. “In our commitment to ongoing evidence development, we are exceptionally proud of the progress we have made regarding DecisionDx-Melanoma. The independent risk-stratification provided by this test has already been demonstrated in numerous retrospective and prospective studies, is supported with 50 peer-reviewed publications, and has been studied in more than 10,000 patients. In 2023, there were two critical peer-reviewed publications demonstrating an association with DecisionDx-Melanoma testing and improved patient outcomes. The first study demonstrated that testing with DecisionDx-Melanoma was associated with lower melanoma-specific and overall mortality relative to untested patients (Bailey et al.), and the second demonstrated that patients who received routine imaging after high-risk DecisionDx-Melanoma test scores had an earlier recurrence diagnosis with lower tumor burden, leading to better clinical outcomes, including improved overall survival (Dhillon et al.). DecisionDx-Melanoma is the only melanoma prognostic test shown to be associated with improved patient survival. “We are optimistic about continued commercial momentum in 2024 and will continue to focus on the needs of the patients and clinicians who drive our business.” Twelve Months Ended Dec. 31, 2023, Financial and Operational Highlights Revenues were $219.8 million, a 60% increase compared to $137.0 million in 2022. Included in revenue for the year were revenue adjustments related to tests delivered in prior periods. These prior period revenue adjustments for the twelve months ended Dec. 31, 2023, were $4.5 million of net negative revenue adjustments, compared to $2.0 million of net negative revenue adjustments for 2022. Adjusted revenues, which exclude the effects of revenue adjustments related to tests delivered in prior periods, were $224.3 million, a 61% increase compared to $139.0 million in 2022. Delivered 70,429 total test reports in 2023, an increase of 59% compared to 44,419 in 2022: DecisionDx-Melanoma test reports delivered in 2023 were 33,330, compared to 27,803 in 2022, an increase of 20%. DecisionDx®-SCC test reports delivered in 2023 were 11,442, compared to 5,967 in 2022, an increase of 92%. MyPath® Melanoma and DiffDx®-Melanoma test reports delivered in 2023 were 3,962, compared to 3,561 in 2022, an increase of 11%. TissueCypher Barrett’s Esophagus test reports delivered in 2023 were 9,100, compared to 2,128 in 2022, an increase of 328%. IDgenetix® test reports delivered in 2023 were 10,921, compared to 3,249 in 2022, an increase of 236%. DecisionDx®-UM test reports delivered in 2023 were 1,674, compared to 1,711 in 2022, a decrease of 2%. Gross margin for 2023 was 75%, and adjusted gross margin was 80%, compared to 71% and 77%, respectively, for the same periods in 2022. Net cash used in operations was $5.6 million, compared to $41.7 million in 2022. Net loss for 2023, which includes non-cash stock-based compensation expense of $51.2 million, was $57.5 million, compared to $67.1 million in 2022. Adjusted EBITDA for 2023 was $(4.4) million, compared to $(42.6) million in 2022. Cash, Cash Equivalents and Marketable Investment Securities As of Dec. 31, 2023, the Company’s cash, cash equivalents and marketable investment securities totaled $243.1 million. Fourth Quarter Ended Dec. 31, 2023, Financial and Operational Highlights Revenues were $66.1 million, a 72% increase compared to $38.3 million during the same period in 2022. Included in revenue for the period were revenue adjustments related to tests delivered in prior periods. These prior period revenue adjustments for the quarter were $4.1 million of net negative revenue adjustments, compared to $0.8 million of net positive revenue adjustments for the same period in 2022. Adjusted revenues, which exclude the effects of revenue adjustments related to tests delivered in prior periods, were $70.2 million, an 87% increase compared to $37.5 million for the same period in 2022. Delivered 20,284 total test reports, an increase of 60% compared to 12,644 in the same period of 2022: DecisionDx-Melanoma test reports delivered in the quarter were 8,591, compared to 7,301 in the fourth quarter of 2022, an increase of 18%. DecisionDx-SCC test reports delivered in the quarter were 3,530, compared to 1,845 in the fourth quarter of 2022, an increase of 91%. MyPath Melanoma test reports delivered in the quarter were 1,018, compared to 822 MyPath Melanoma and DiffDx-Melanoma aggregate test reports in the fourth quarter of 2022, an increase of 24%. TissueCypher Barrett’s Esophagus test reports delivered in the quarter were 3,441, compared to 1,030 in the fourth quarter of 2022, an increase of 234%. IDgenetix test reports delivered in the quarter were 3,299, compared to 1,214 in the fourth quarter of 2022, an increase of 172%. DecisionDx-UM test reports delivered in the quarter were 405, compared to 432 in the fourth quarter of 2022, a decrease of 6%. Gross margin was 78%, and adjusted gross margin was 82%, compared to 69% and 75%, respectively, for the same periods in 2022. Net cash provided by operations was $18.6 million, compared to net cash used in operations of $6.0 million for the same period in 2022. Net loss, which includes non-cash stock-based compensation expense of $11.8 million, was $2.6 million, compared to a net loss of $20.6 million for the same period in 2022. Adjusted EBITDA was $9.4 million, compared to $(10.4) million for the same period in 2022. 2024 Outlook The Company anticipates generating between $235-240 million in total revenue in 2024. Fourth Quarter and Recent Accomplishments and Highlights Dermatology DecisionDx-Melanoma: In December 2023, the Company announced the publication of a study in the Journal of the Advanced Practitioner in Oncology that assessed the viewpoints of nurse practitioners and physician assistants (NPs/PAs) toward the clinical use of DecisionDx-Melanoma in patients diagnosed with cutaneous melanoma (CM). The study found that more than 90% of the NPs/PAs who completed a survey about DecisionDx-Melanoma believe that prognostic (i.e., risk-stratification) information about a patient’s melanoma is valuable and improves patient care. See the Company’s news release from Dec. 1, 2023, for more information. DecisionDx-Melanoma: In February 2024, the Company announced the publication of a study in Cancers demonstrating that DecisionDx-Melanoma provided significantly better risk stratification than American Joint Committee on Cancer 8th Edition (AJCC8) staging in patients with stage I CM. This study reports the results of two large stage I cohorts, including 5,561 patients from the National Cancer Institute’s Surveillance, Epidemiology and End Results (SEER) Program Registries. It supports incorporating the DecisionDx-Melanoma test into clinical practice to help clinicians and patients with stage I melanoma obtain more precise information about a patient’s risk of disease progression to inform more personalized, risk-aligned treatment and surveillance management plans. DecisionDx-SCC: In January 2024, the Company announced the publication of a new study in the Journal of Clinical and Aesthetic Dermatology (JCAD), which found that guiding adjuvant radiation treatment (ART) using DecisionDx-SCC results can lead to substantial Medicare healthcare savings of up to approximately $972 million annually. This cost reduction is primarily attributed to avoiding direct costs of unnecessary ART in patients with low-risk DecisionDx-SCC profiles and the appropriate selection of patient treatment based on molecular risk assessment. Additionally, integrating the objective DecisionDx-SCC test into the management of ART-eligible high-risk cutaneous squamous cell carcinoma (SCC) can identify those who may safely avoid ART who would, therefore, have reduced complications, a net improvement in health outcomes and reduced cost in the Medicare population. See the Company’s news release from Jan. 18, 2024, for more information. DecisionDx-SCC: In February 2024, the Company announced the publication of an expert consensus article in JCAD related to its DecisionDx-SCC test. The expert multidisciplinary panel included radiation oncologists and dermatologists/Mohs micrographic surgeons with expertise in SCC management and provides risk-based clinical recommendations and a workflow for use of ART in patients with high-risk SCC to control disease progression. The suggested workflow integrates DecisionDx-SCC testing and AJCC8 staging, based on clinicopathologic risk factors, with the current National Comprehensive Cancer Network (NCCN) guidelines to improve precision in ART recommendations based on which patients are at the highest risk for metastasis and most likely to benefit from treatment. In February 2024, the Company was notified that a new study, titled “Inconsistent associations between risk factor profiles and adjuvant radiation therapy (ART) treatment in patients with cutaneous squamous cell carcinoma and utility of the 40-gene expression pro refine ART guidance,” was accepted for publication in Dermatology and Therapy. The study shows that including tumor biology-based risk stratification from the DecisionDx-SCC test in ART decisions can refine risk and identify appropriate SCC patients who are likely to benefit from ART treatment, as well as those who can consider deferring it. In February 2024, the Company was notified that a new study, titled “Integrating the 40-gene expression profile (40-GEP) test improves metastatic risk-stratification within clinically relevant subgroups of high-risk cutaneous squamous cell carcinoma (cSCC) patients,” was accepted for publication in Dermatology and Therapy. The study of 897 patients analyzed the independent performance of DecisionDx-SCC from risk factors and staging systems, and demonstrated improved predictive accuracy when integrated with the NCCN, Brigham and Women’s Hospital (BWH) and AJCC8 clinicopathologic risk assessment systems to significantly enhance risk-aligned treatment for patients. Gastroenterology In October 2023, the Company announced new data demonstrating the significant clinical utility of its TissueCypher Barrett’s Esophagus test in guiding risk-aligned upstaging of care for patients with non-dysplastic Barrett’s esophagus (BE) at a higher risk of progression to high-grade dysplasia or esophageal adenocarcinoma than indicated by their clinicopathologic risk factors. See the Company’s news release from Oct. 2, 2023, for more information. Mental Health In November 2023, the Company announced data from a single-site, open-label study demonstrating the consistent impact of IDgenetix on medication response and remission rates in patients with major depressive disorder (MDD). The study found that real-world patient outcomes were strongly aligned to the results of a previously published randomized controlled trial that demonstrated IDgenetix-guided medication management significantly improved response and remission rates for patients with MDD. See the Company’s news release from Nov. 8, 2023, for more information. Pipeline Initiatives Uveal Melanoma: In November 2023, the Company announced new discovery data from an ongoing study exploring the potential for developing a minimally invasive test, complementary to DecisionDx-UM, to evaluate small, suspicious lesions of uncertain malignant potential in patients’ eyes. See the Company’s news release from Nov. 3, 2023, for more information. Inflammatory Skin Disease: In November 2023, the Company announced new data showing the ability of its pipeline test in development to distinguish between responders and non-responders to an atopic dermatitis (AD) therapy and also distinguish between AD, psoriasis (PSO) and mycosis fungoides (MF) skin lesions. Additional updates regarding development of this pipeline program are expected in 2024. See the Company’s news release from Nov. 2, 2023, for more information. Corporate In November 2023, the Company announced that it was named a Houston Chronicle Top Workplace for the third year in a row and awarded three new Culture Excellence awards, recognizing the Company in the areas of Employee Appreciation, Employee Well-Being and Professional Development. See the Company’s news release from Nov. 13, 2023, for more information. In January 2024, the Company announced that its chief operating officer, Kristen Oelschlager, was named to The Healthcare Technology Report’s Top 25 Women Leaders in Biotechnology of 2023. The honorees “stand as a driving force, ensuring diverse perspectives on scientific breakthroughs and groundbreaking therapies,” according to the publication. See the Company’s news release from Jan. 9, 2024, for more information. Conference Call and Webcast Details Castle Biosciences will hold a conference call on Wednesday, Feb. 28, 2024, at 4:30 p.m. Eastern time to discuss its fourth quarter and full-year 2023 results and provide a corporate update. A live webcast of the conference call can be accessed here: or via the webcast link on the Investor Relations page of the Company’s website, . Please access the webcast at least 10 minutes before the conference call start time. An archive of the webcast will be available on the Company’s website until March 20, 2024. To access the live conference call via phone, please dial 833 470 1428 from the United States, or +1 404 975 4839 internationally, at least 10 minutes prior to the start of the call, using the conference ID 036526. There will be a brief Question & Answer session following management commentary. Use of Non-GAAP Financial Measures (UNAUDITED) In this release, we use the metrics of Adjusted Revenues, Adjusted Gross Margin and Adjusted EBITDA, which are non-GAAP financial measures and are not calculated in accordance with generally accepted accounting principles in the United States (GAAP). Adjusted Revenues and Adjusted Gross Margin reflect adjustments to GAAP net revenues to exclude net positive and/or net negative revenue adjustments recorded in the current period associated with changes in estimated variable consideration related to test reports delivered in previous periods. Adjusted Gross Margin further excludes acquisition-related intangible asset amortization. Adjusted EBITDA excludes from net loss: interest income, interest expense, income tax expense (benefit), depreciation and amortization expense, stock-based compensation expense, change in fair value of contingent consideration and acquisition related transaction costs. We use Adjusted Revenues, Adjusted Gross Margin and Adjusted EBITDA internally because we believe these metrics provide useful supplemental information in assessing our revenue and operating performance reported in accordance with GAAP, respectively. We believe that Adjusted Revenues, when used in conjunction with our test report volume information, facilitates investors’ analysis of our current-period revenue performance and average selling price performance by excluding the effects of revenue adjustments related to test reports delivered in prior periods, since these adjustments may not be indicative of the current or future performance of our business. We believe that providing Adjusted Revenues may also help facilitate comparisons to our historical periods. Adjusted Gross Margin is calculated using Adjusted Revenues and therefore excludes the impact of revenue adjustments related to test reports delivered in prior periods, which we believe is useful to investors as described above. We further exclude acquisition-related intangible asset amortization in the calculation of Adjusted Gross Margin. We believe that excluding acquisition-related intangible asset amortization may facilitate gross margin comparisons to historical periods and may be useful in assessing current-period performance without regard to the historical accounting valuations of intangible assets, which are applicable only to tests we acquired rather than internally developed. We believe Adjusted EBITDA may enhance an evaluation of our operating performance because it excludes the impact of prior decisions made about capital investment, financing, investing and certain expenses we believe are not indicative of our ongoing performance. However, these non-GAAP financial measures may be different from non-GAAP financial measures used by other companies, even when the same or similarly titled terms are used to identify such measures, limiting their usefulness for comparative purposes. These non-GAAP financial measures are not meant to be considered in isolation or used as substitutes for net revenues, gross margin or net loss reported in accordance with GAAP; should be considered in conjunction with our financial information presented in accordance with GAAP; have no standardized meaning prescribed by GAAP; are unaudited; and are not prepared under any comprehensive set of accounting rules or principles. In addition, from time to time in the future, there may be other items that we may exclude for purposes of these non-GAAP financial measures, and we may in the future cease to exclude items that we have historically excluded for purposes of these non-GAAP financial measures. Likewise, we may determine to modify the nature of adjustments to arrive at these non-GAAP financial measures. Because of the non-standardized definitions of non-GAAP financial measures, the non-GAAP financial measure as used by us in this press release and the accompanying reconciliation tables have limits in their usefulness to investors and may be calculated differently from, and therefore may not be directly comparable to, similarly titled measures used by other companies. Accordingly, investors should not place undue reliance on non-GAAP financial measures. Reconciliations of these non-GAAP financial measures to the most directly comparable GAAP financial measures are presented in the tables at the end of this release. About Castle Biosciences Castle Biosciences (Nasdaq: CSTL) is a leading diagnostics company improving health through innovative tests that guide patient care. The Company aims to transform disease management by keeping people first: patients, clinicians, employees and investors. Castle’s current portfolio consists of tests for skin cancers, Barrett’s esophagus, mental health conditions and uveal melanoma. Additionally, the Company has active research and development programs for tests in other diseases with high clinical need, including its test in development to help guide systemic therapy selection for patients with moderate-to-severe, atopic dermatitis, psoriasis and related conditions. To learn more, please visit and connect with us on LinkedIn, Facebook, X and Instagram. DecisionDx-Melanoma, DecisionDx-CMSeq, DecisionDx-SCC, MyPath Melanoma, DiffDx-Melanoma, TissueCypher, IDgenetix, DecisionDx-UM, DecisionDx-PRAME and DecisionDx-UMSeq are trademarks of Castle Biosciences, Inc. Forward-Looking Statements This press release contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended, which are subject to the “safe harbor” created by those sections. These forward-looking statements include, but are not limited to, statements concerning our expectations regarding: (i) the potential of our tests to improve patient outcomes, including increased survival; (ii) our continued commercial momentum in 2024; (iii) the ability of DecisionDx-Melanoma to provide prognostic information about a patient’s melanoma and improve patient care; (iv) the ability of DecisionDx-SCC to lead to substantial Medicare healthcare savings and to provide benefits related to reduced complications, a net improvement in health outcomes, reduced cost in the Medicare population and improved stratification of metastatic risk; (v) the ability of our TissueCypher BE test to guide risk-aligned upstaging of care; (vi) the ability of IDgenetix-guided medication management to significantly improve response and remission rates for patients with MDD; (vii) the potential for developing a minimally invasive test, complementary to DecisionDx-UM, to evaluate small, suspicious lesions of uncertain malignant potential in patients’ eyes; and (viii) the ability of our pipeline test in development to distinguish between responders and non-responders to an AD therapy and also distinguish between AD, psoriasis and mycosis fungoides skin lesions. The words “anticipate,” “can,” “could,” “expect,” “goal,” “may,” “plan” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. We may not actually achieve the plans, intentions, or expectations disclosed in our forward-looking statements and you should not place undue reliance on our forward-looking statements. Actual results or events could differ materially from the plans, intentions and expectations disclosed in the forward-looking statements that we make. These forward-looking statements involve risks and uncertainties that could cause our actual results to differ materially from those in the forward-looking statements, including, without limitation: our assumptions or expectations regarding continued reimbursement for our DecisionDx-SCC test at the current rate and reimbursement for our other products and subsequent coverage decisions, our estimated total addressable markets for our products and product candidates and the related expenses, capital requirements and potential needs for additional financing, the anticipated cost, timing and success of our product candidates, and our plans to research, develop and commercialize new tests and our ability to successfully integrate new businesses, assets, products or technologies acquired through acquisitions, the effects of macroeconomic events and conditions, including inflation and monetary supply shifts, labor shortages, liquidity concerns at, and failures of, banks and other financial institutions or other disruptions in the banking system or financing markets and recession risks, supply chain disruptions, outbreaks of contagious diseases and geopolitical events (such as the ongoing Israel-Hamas War and Ukraine-Russia conflict), among others, on our business and our efforts to address its impact on our business; subsequent study or trial results and findings may contradict earlier study or trial results and findings or may not support the results discussed in this press release, including with respect to the tests discussed in this press release; our planned installation of additional equipment and supporting technology infrastructures and implementation of certain process efficiencies may not enable us to increase the future scalability of our TissueCypher Test; actual application of our tests may not provide the aforementioned benefits to patients; our newer gastroenterology and mental health franchises may not contribute to the achievement of our long-term financial targets as anticipated; and the risks set forth under the heading “Risk Factors” in our Annual Report on Form 10-K for the year ended December 31, 2023, each filed or to be filed with the SEC, and in our other filings with the SEC. The forward-looking statements are applicable only as of the date on which they are made, and we do not assume any obligation to update any forward-looking statements, except as may be required by law. CASTLE BIOSCIENCES, INC. CONDENSED CONSOLIDATED STATEMENTS OF OPERATIONS (in thousands, except per share data) Three Months Ended December 31, Twelve Months Ended December 31, 2023 2022 2023 2022 (unaudited) (unaudited) NET REVENUES $ 66,120 $ 38,338 $ 219,788 $ 137,039 OPERATING EXPENSES AND OTHER OPERATING INCOME Cost of sales (exclusive of amortization of acquired intangible asset) 12,423 9,520 44,982 32,009 Research and development 12,994 11,309 53,618 44,903 Selling, general and administrative 44,090 38,426 180,152 143,003 Amortization of acquired intangible assets 2,271 2,215 9,013 8,266 Change in fair value of contingent consideration — (300 ) — (18,287 ) Total operating expenses, net 71,778 61,170 287,765 209,894 Operating loss (5,658 ) (22,832 ) (67,977 ) (72,855 ) Interest income and other non-operating income 3,119 2,275 10,623 3,968 Interest expense (2 ) (4 ) (11 ) (17 ) Loss before income taxes (2,541 ) (20,561 ) (57,365 ) (68,904 ) Income tax expense (benefit) 39 57 101 (1,766 ) Net loss $ (2,580 ) $ (20,618 ) $ (57,466 ) $ (67,138 ) Loss per share, basic and diluted $ (0.10 ) $ (0.78 ) $ (2.14 ) $ (2.58 ) Weighted-average shares outstanding, basic and diluted 27,030 26,400 26,802 26,054 Stock-Based Compensation Expense Stock-based compensation expense is included in the condensed consolidated statements of operations as follows (in thousands): Three Months Ended December 31, Twelve Months Ended December 31, 2023 2022 2023 2022 (unaudited) (unaudited) Cost of sales (exclusive of amortization of acquired intangible assets) $ 1,219 $ 1,030 $ 4,938 $ 3,755 Research and development 2,364 2,028 10,119 7,635 Selling, general and administrative 8,219 6,865 36,162 24,931 Total stock-based compensation expense $ 11,802 $ 9,923 $ 51,219 $ 36,321 CASTLE BIOSCIENCES, INC. CONDENSED CONSOLIDATED STATEMENTS OF COMPREHENSIVE LOSS (in thousands) Three Months Ended December 31, Twelve Months Ended December 31, 2023 2022 2023 2022 (unaudited) (unaudited) Net loss $ (2,580 ) $ (20,618 ) $ (57,466 ) $ (67,138 ) Other comprehensive loss: Net unrealized gain (loss) on available-for-sale securities 207 (192 ) 517 (381 ) Comprehensive loss $ (2,373 ) $ (20,810 ) $ (56,949 ) $ (67,519 ) CASTLE BIOSCIENCES, INC. CONDENSED CONSOLIDATED BALANCE SHEETS (in thousands) December 31, 2023 December 31, 2022 ASSETS Current Assets Cash and cash equivalents $ 98,841 $ 122,948 Marketable investment securities 144,258 135,677 Accounts receivable, net 38,302 23,476 Inventory 7,942 3,980 Prepaid expenses and other current assets 6,292 6,207 Total current assets 295,635 292,288 Long-term accounts receivable, net 1,191 1,087 Property and equipment, net 25,433 14,315 Operating lease assets 12,306 12,181 Goodwill and other intangible assets, net 117,335 126,348 Other assets – long-term 1,440 1,110 Total assets $ 453,340 $ 447,329 LIABILITIES AND STOCKHOLDERS’ EQUITY Current Liabilities Accounts payable $ 10,268 $ 4,731 Accrued compensation 28,945 24,358 Operating lease liabilities 1,137 1,777 Other accrued and current liabilities 7,317 5,262 Total current liabilities 47,667 36,128 Noncurrent operating lease liabilities 14,173 11,533 Deferred tax liability 206 428 Other liabilities 25 90 Total liabilities 62,071 48,179 Stockholders’ Equity Common Stock 27 27 Additional paid-in capital 609,477 560,409 Accumulated deficit (218,371 ) (160,905 ) Accumulated other comprehensive income (loss) 136 (381 ) Total stockholders’ equity 391,269 399,150 Total liabilities and stockholders’ equity $ 453,340 $ 447,329 CASTLE BIOSCIENCES, INC. CONDENSED CONSOLIDATED STATEMENTS OF CASH FLOWS (in thousands) Twelve Months Ended December 31, 2023 2022 OPERATING ACTIVITIES Net loss $ (57,466 ) $ (67,138 ) Adjustments to reconcile net loss to net cash used in operating activities: Depreciation and amortization 12,330 10,543 Stock-based compensation expense 51,219 36,321 Change in fair value of contingent consideration — (18,287 ) Deferred income taxes (223 ) (1,877 ) Accretion of discounts on marketable investment securities (5,491 ) (1,368 ) Other 635 158 Change in operating assets and liabilities: Accounts receivable (14,930 ) (6,218 ) Prepaid expenses and other current assets (435 ) (1,224 ) Inventory (3,962 ) (1,680 ) Operating lease assets (258 ) 991 Other assets (330 ) 618 Accounts payable 5,707 582 Operating lease liabilities 852 (608 ) Accrued compensation 4,587 8,495 Other accrued and current liabilities 2,139 (963 ) Net cash used in operating activities (5,626 ) (41,655 ) INVESTING ACTIVITIES Purchases of property and equipment (13,621 ) (5,632 ) Asset acquisitions, net of cash and cash equivalents acquired — 547 Acquisition of business, net of cash and cash equivalents acquired — (26,966 ) Proceeds from sale of property and equipment 13 195 Purchases of marketable investment securities (189,075 ) (134,689 ) Proceeds from maturities of marketable investment securities 186,500 — Net cash used in investing activities (16,183 ) (166,545 ) FINANCING ACTIVITIES Proceeds from exercise of common stock options 269 833 Payment of employees’ taxes on vested restricted stock units (5,134 ) (1,688 ) Proceeds from contributions to the employee stock purchase plan 2,709 2,492 Repayment of principal portion of finance lease liabilities (142 ) (122 ) Net cash (used in) provided by financing activities (2,298 ) 1,515 NET CHANGE IN CASH AND CASH EQUIVALENTS (24,107 ) (206,685 ) Beginning of year 122,948 329,633 End of year $ 98,841 $ 122,948 CASTLE BIOSCIENCES, INC. Reconciliation of Non-GAAP Financial Measures (UNAUDITED) The table below presents the reconciliation of adjusted revenues and adjusted gross margin, which are non-GAAP financial measures. See "Use of Non-GAAP Financial Measures (UNAUDITED)" above for further information regarding the Company's use of non-GAAP financial measures. Three Months Ended December 31, Twelve Months Ended December 31, 2023 2022 2023 2022 (in thousands) Adjusted revenues Net revenues (GAAP) $ 66,120 $ 38,338 $ 219,788 $ 137,039 Revenue associated with test reports delivered in prior periods 4,086 (806 ) 4,476 1,987 Adjusted revenues (Non-GAAP) $ 70,206 $ 37,532 $ 224,264 $ 139,026 Adjusted gross margin Gross margin (GAAP)1 $ 51,426 $ 26,603 $ 165,793 $ 96,764 Amortization of acquired intangible assets 2,271 2,215 9,013 8,266 Revenue associated with test reports delivered in prior periods 4,086 (806 ) 4,476 1,987 Adjusted gross margin (Non-GAAP) $ 57,783 $ 28,012 $ 179,282 $ 107,017 Gross margin percentage (GAAP)2 77.8 % 69.4 % 75.4 % 70.6 % Adjusted gross margin percentage (Non-GAAP)3 82.3 % 74.6 % 79.9 % 77.0 % _____________ 1. Calculated as net revenues (GAAP) less the sum of cost of sales (exclusive of amortization of acquired intangible assets) and amortization of acquired intangible assets. 2. Calculated as gross margin (GAAP) divided by net revenues (GAAP). 3. Calculated as adjusted gross margin (Non-GAAP) divided by adjusted revenues (Non-GAAP). The table below presents the reconciliation of adjusted EBITDA, which is a non-GAAP financial measure. See "Use of Non-GAAP Financial Measures (UNAUDITED)" above for further information regarding the Company's use of non-GAAP financial measures. Three Months Ended December 31, Twelve Months Ended December 31, 2023 2022 2023 2022 (in thousands) Adjusted EBITDA Net loss $ (2,580 ) $ (20,618 ) $ (57,466 ) $ (67,138 ) Interest income (3,119 ) (2,275 ) (10,623 ) (3,968 ) Interest expense 2 4 11 17 Income tax expense (benefit) 39 57 101 (1,766 ) Depreciation and amortization expense 3,224 2,841 12,330 10,543 Stock-based compensation expense 11,802 9,923 51,219 36,321 Change in fair value of contingent consideration — (300 ) — (18,287 ) Acquisition related transaction costs — — — 1,711 Adjusted EBITDA (Non-GAAP) $ 9,368 $ (10,368 ) $ (4,428 ) $ (42,567 )