Docetaxel

FG-3246 showed encouraging anti-cancer activity with an acceptable safety profile in patients with metastatic castration-resistant prostate cancer Initiation of Phase 2 monotherapy dose optimization study of FG-3246 in mCRPC expected by mid-2025 SAN FRANCISCO, March 28, 2025 (GLOBE NEWSWIRE) -- FibroGen, Inc. (NASDAQ: FGEN) today announced the peer-reviewed publication titled “A Phase 1, First-in-Human Study of FOR46 (FG-3246), an Immune-Modulating Antibody-Drug Conjugate Targeting CD46, in Patients with Metastatic Castration Resistant Prostate Cancer” in the Journal of Clinical Oncology. The manuscript includes the complete results from the Fortis Therapeutics-sponsored Phase 1 study of FOR46 (now known as FG-3246), a potential first-in-class anti-CD46 antibody drug conjugate (ADC) with an MMAE-containing payload, in patients with metastatic castration-resistant prostate cancer (mCRPC). “I am excited to see the results from the Phase 1 monotherapy study of FOR46 (FG-3246) published in the Journal of Clinical Oncology. This is the first clinical trial targeting CD46 in patients with prostate cancer, and the totality of the data highlights the promising potential of FG-3246 anti-cancer activity, especially when considering the unselected, heavily pre-treated patient population in the trial. The trial results provide key insights into the potential clinical impact of targeting CD46 in the treatment of mCRPC and support its further development in this disease space with high unmet need,” said Dr. Rahul Aggarwal, Professor of Medicine at the University of California San Francisco, and Principal Investigator of the study. “We are looking forward to advancing FG-3246 in the clinic and remain on track for initiating the Phase 2 monotherapy study by mid-2025 as well as disclosing topline results from the combination trial of FG-3246 and enzalutamide in the second half of 2025,” added Thane Wettig, Chief Executive Officer of FibroGen. “FG-3246 represents a potential first-in-class, non-PSMA approach to treating mCRPC and we, along with the medical community, are excited about the potential for CD46 to become a next generation target in the prostate cancer treatment paradigm.” This Phase 1 study was a multi-center, first-in-human, open label dose escalation and expansion study evaluating the safety, tolerability, and anti-tumor activity as measured by the decline of prostate-specific antigen (PSA) from baseline, objective tumor response rate in patients with measurable disease, and radiographic progression free survival (rPFS). The completed Phase 1 trial includes a total of 56 patients from the dose-escalation and dose-expansion cohorts. Notably, patients were biomarker unselected and heavily pre-treated, having received a median of 5 lines of therapy prior to receiving FG-3246. Key highlights from the publication include: The maximally tolerated dose of FG-3246 was 2.7 mg/kg by adjusted body weight (AjBW) every 3 weeks The most frequent adverse events were consistent with other MMAE-based ADCs and included infusion related reactions (48.2%), neutropenia (41.1%), and peripheral neuropathy (32.1%). Ocular adverse events were infrequent, which may be a distinguishing feature compared with other MMAE-based ADCs Efficacy observed in the RECIST-evaluable set of 25 patients: Confirmed objective response rate was 20% with median duration of response of 7.5 months All objective responses observed at a starting dose of 2.7 mg/kg or higher Disease control rate was 80% with duration of treatment exceeding 24 weeks in 12 patients (48%) PSA50 response rate of 36% in 39 evaluable patients Of eight evaluable patients who received docetaxel in the castration-sensitive setting, four (50%) achieved a confirmed PSA50 response Median radiographic progression-free survival of 8.7 months in all 40 subjects in the efficacy analysis set Of 15 evaluable baseline tumors, 12 (80%) were positive for CD46 expression by immunohistochemistry FG-3246 responders were found to have a significantly higher frequency of effector T cells and lower frequency of immunosuppressive myeloid cells Ocular adverse events were infrequent, which may be a distinguishing feature compared with other MMAE-based ADCs Confirmed objective response rate was 20% with median duration of response of 7.5 months All objective responses observed at a starting dose of 2.7 mg/kg or higher Disease control rate was 80% with duration of treatment exceeding 24 weeks in 12 patients (48%) All objective responses observed at a starting dose of 2.7 mg/kg or higher Of eight evaluable patients who received docetaxel in the castration-sensitive setting, four (50%) achieved a confirmed PSA50 response The Company anticipates initiating the Phase 2 monotherapy dose optimization study of FG-3246 in patients with mCRPC by mid-2025. FG-3246 is also being evaluated in combination with enzalutamide in an investigator-sponsored study with topline results from the Phase 2 portion of the study anticipated in 2H 2025. About the Phase 1 Study FOR46-001 (NCT03575819) is a Phase 1, dose-escalation study sponsored by Fortis Therapeutics to evaluate multiple doses of IV-administered FG-3246 (also known as FOR46) in patients with mCRPC who have progressive disease on at least one ARSI, followed by a dose-expansion cohort, to evaluate the safety, tolerability, PK, biological activity, and preliminary evidence of anti-tumor activity of FG-3246 in this patient population. Thirty-three (33) patients were enrolled in the dose-escalation phase of the study at doses between 0.1 mg/kg and 3.0 mg/kg every three weeks (Q3W), with adjusted body weight dosing (AjBW) used at most dose levels above 2.1 mg/kg. Safety and tolerability of FG-3246 were evaluated in the dose-escalation period of the study. Twenty-three (23) patients were enrolled in the dose-expansion period of the study; 18 patients with adenocarcinoma mCRPC (Cohort 1) and five patients with neuroendocrine prostate cancer (Cohort 2). All patients in the expansion cohorts were treated at 2.7 mg/kg AjBW to a maximum of 270 mg every three weeks. The safety profile of FG-3246 was characterized, and anti-tumor activity of FG-3246 in adenocarcinoma patients dosed at ≥ 1.2 mg/kg was evaluated. About Metastatic Castration-Resistant Prostate Cancer Prostate cancer is the second most common malignancy in men, contributing significantly to male mortality rates. Approximately 13% of men will be diagnosed with prostate cancer at some point during their lifetime. There are about 65,000 drug treatable mCRPC cases in the U.S. annually and 5-year survival in mCRPC is approximately 30%1. About FG-3246 FG-3246 (also known as FOR46) is a potential first-in-class, fully human antibody-drug conjugate (ADC), exclusively in-licensed from Fortis Therapeutics, and is being developed by FibroGen for metastatic castration-resistant prostate cancer and other tumor types. FG-3246 binds to an epitope of CD46, a cell receptor target, that induces internalization upon antibody binding, is present at high levels in prostate cancer and other tumor types and demonstrates very limited expression in most normal tissues. FG-3246 is comprised of an anti-CD46 antibody, YS5, linked to the anti-mitotic agent, MMAE, which is a clinically and commercially validated ADC payload. FG-3246 has demonstrated anti-tumor activity in both preclinical and clinical studies. FG-3246 is currently in an ongoing Phase 1/2 study being conducted at UCSF to evaluate it in combination with enzalutamide with topline data from the Phase 2 portion of the study expected in the second half of 2025, and a biomarker trial using a PET biomarker for CD46 using the same antibody backbone. We anticipate the initiation of the Phase 2 monotherapy dose optimization trial in metastatic castration-resistant prostate cancer by mid-2025. FG-3246 is an investigational drug and not approved for marketing by any regulatory authority. About FibroGen FibroGen, Inc. is a biopharmaceutical company focused on development of novel therapies at the frontiers of cancer biology and anemia. Roxadustat (爱瑞卓®, EVRENZOTM) is currently approved in China, Europe, Japan, and numerous other countries for the treatment of anemia in chronic kidney disease (CKD) patients on dialysis and not on dialysis. The Company continues to evaluate a development plan for roxadustat in anemia associated with lower-risk myelodysplastic syndrome (LR-MDS) in the U.S. FG-3246 (also known as FOR46), a first-in-class antibody-drug conjugate (ADC) targeting CD46 is in development for the treatment of metastatic castration-resistant prostate cancer. This program also includes the development of FG-3180, an associated CD46-targeted PET biomarker. For more information, please visit www.fibrogen.com. Forward-Looking Statements This release contains forward-looking statements regarding FibroGen’s strategy, future plans and prospects, including statements regarding its commercial products and clinical programs and those of its collaboration partners Fortis and UCSF. These forward-looking statements include, but are not limited to, statements regarding the efficacy, safety, and potential clinical or commercial success of FibroGen products and product candidates, and statements about FibroGen’s plans and objectives. These forward-looking statements are typically identified by use of terms such as “may,” “will”, “should,” “on track,” “could,” “expect,” “plan,” “anticipate,” “believe,” “estimate,” “predict,” “potential,” “continue” and similar words, although some forward-looking statements are expressed differently. FibroGen’s actual results may differ materially from those indicated in these forward-looking statements due to risks and uncertainties related to the continued progress and timing of its various programs, including the enrollment and results from ongoing and potential future clinical trials, and other matters that are described in FibroGen’s Annual Report on Form 10-K for the most recent fiscal year, and any more recent Quarterly Reports on Form 10-Q, each as filed with the Securities and Exchange Commission (SEC), including the risk factors set forth therein. Investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date of this release, and FibroGen undertakes no obligation to update any forward-looking statement in this press release, except as required by law. References: 1. Seer.cancer.gov https://seer.cancer.gov/statfacts/html/prost.html For Investor Inquiries: David DeLucia, CFA Senior Vice President and Chief Financial Officer ir@fibrogen.com Source: FibroGen, Inc.

Plinabulin Final Phase 3 Data Published in The Lancet Respiratory Medicine, Demonstrating Overall Survival Benefit in 2L/3L NSCLC EGFR Wild Type vs. DocetaxelPlinabulin Phase 2 Data Highlights Potential to Resensitize Tumors Progressed on PD-1/PD-L1 Inhibitors in Metastatic NSCLCSEED Therapeutics Enters into Targeted Protein Degradation Research Collaboration with Eisai with potential payment to SEED of up to $1.5 Billion and Completes $24 Million First Close of Series A-3 FinancingSEED Therapeutics’ Lead Oncology Asset RBM39 Degrader Granted Rare Pediatric Disease and Orphan Drug Designations by the FDA FLORHAM PARK, N.J., March 27, 2025 (GLOBE NEWSWIRE) -- BeyondSpring Inc. (NASDAQ: BYSI) (“BeyondSpring” or the “Company”), a global clinical-stage biopharmaceutical company developing innovative cancer therapies, today announced its financial results for the year ended December 31, 2024, and provided a business update on key clinical and corporate developments. “2024 was a pivotal year for BeyondSpring, with significant clinical progress for our first-in-class agent Plinabulin and strategic advancements for SEED Therapeutics (SEED), which BeyondSpring co-founded and owns an equity stake in. We believe these developments create value benefiting all stakeholders,” said Dr. Lan Huang, Co-Founder, Chairman, and CEO of BeyondSpring. “Plinabulin demonstrated a statistically significant survival benefit in patients with second- and third-line non-small cell lung cancer (NSCLC) (EGFR wild-type), a setting where no new therapies have been approved in over a decade. This Phase 3 data, now published in The Lancet Respiratory Medicine, strengthens our regulatory strategy as we prepare for submission to the Chinese National Medical Products Administration (NMPA) and potentially regulatory authorities in other jurisdictions.” “BeyondSpring is also advancing Plinabulin’s potential as a next-generation immuno-oncology agent, with its potent effect in dendritic cell maturation. An ongoing Phase 2 study showed that Plinabulin, in combination with a PD-1 inhibitor and docetaxel, produced promising efficacy in patients with metastatic NSCLC who had progressed on prior PD-1/PD-L1 inhibitors with good tolerability. While PD-1 and PD-L1 antibody annual sales have exceeded $50 billion, with most sales coming from lung cancer, 60% of patients across multiple cancer indications develop acquired resistance to checkpoint inhibitors, which we believe represents a significant opportunity for Plinabulin to impact the treatment landscape and create substantial value.” “SEED also made significant progress in 2024, securing a strategic research collaboration with Eisai Co., Ltd. (“Eisai”), a second global pharma partnership in addition to the Eli Lilly and Company (“Lilly”) partnership. Under this collaboration, SEED will be eligible to receive upfront payments and potential preclinical, clinical, regulatory and sales milestone payments of up to $1.5 billion, plus tiered royalties on net sales. In parallel, SEED is advancing its internal lead oncology asset, RBM39 degrader, toward clinical development. SEED’s recognition in two Nature review papers as a leader in targeted protein degradation (TPD), along with recent granting of Rare Pediatric Disease and Orphan Drug Designations by the FDA for its RBM39 degrader ST-01156, further underscore its unique platform and reinforce its leadership in this emerging field.” “With strongly anchored pipelines, key global partnerships and deliberate plans to navigate regulatory pathways, we believe BeyondSpring and SEED are well-positioned to drive transformative advancements in oncology and TPD in 2025,” Dr. Lan Huang concluded. Recent Clinical and Business Updates Plinabulin Clinical Updates Plinabulin Phase 3 Data Published in The Lancet Respiratory Medicine and Presented at the IASLC 2024 conference Demonstrated a statistically significant overall survival, PFS and ORR benefit in second- and third-line NSCLC (EGFR wild-type) compared to standard-of-care docetaxel.Supports planned regulatory submissions to NMPA and potentially regulatory authorities in other jurisdictions. Plinabulin Combination Therapy in multiple cancers which failed PD-1/PD-L1 therapies at MD Anderson Cancer Center Phase 1 investigator-initiated study of Plinabulin + PD-1/PD-L1 inhibitor + radiation showed encouraging data in re-sensitizing NSCLC, Head and Neck cancer, and Hodgkin’s Lymphoma.Responding patients showed dendritic cell maturation. Plinabulin Combination Therapy in NSCLC Ongoing Phase 2 investigator-initiated study (Study 303) of Plinabulin + PD-1 inhibitor + Docetaxel showed encouraging efficacy and safety outcomes in metastatic NSCLC patients who had progressed on prior PD-1/PD-L1 inhibitors.Supports Plinabulin’s potential to resensitize tumors to checkpoint inhibitors. Other Ongoing Clinical Trial Enrolled first patient in a Phase 2 investigator-initiated study (Study 302) of Plinabulin + PD-1 inhibitor + Etoposide/Platinum (EP) for first-line extensive-stage small-cell lung cancer (ES-SCLC). BeyondSpring Business Update Entered into definitive agreements to sell a portion of BeyondSpring’s Series A-1 Preferred Shares of SEED for gross proceeds of approximately $35.4 million to advance late-stage clinical development of Plinabulin. First closing of approximately $7.35 million completed in February 2025. SEED Updates Strategic Collaborations & Financing Research collaboration with Eisai to develop molecular glue degraders for oncology and neurodegenerative diseases with potential payments to SEED of up to $1.5 billion.$24 million Series A-3 financing first close, led by Eisai.Achieved third milestone with Lilly R&D collaboration. Industry Recognition & FDA Designations SEED was recognized in two Nature review articles as a leading company in TPD.Received Rare Pediatric Disease and Orphan Drug Designations from the FDA for RBM39 degrader ST-01156, reinforcing its potential as a breakthrough therapy for hard-to-treat cancers. Full-Year 2024 Financial Results1Continuing operations: R&D expenses: $2.6 million (vs. $7.3 million in 2023), reflecting completion of Plinabulin Dublin-3 and Protective Studies.G&A expenses: $6.1 million (vs. $7.8 million in 2023), driven by cost optimization measures.Net loss: $8.9 million (vs. $14.0 million in 2023).Cash, cash equivalents, and short-term investments: $2.9 million as of December 31, 2024. Discontinued operations: Net loss: $7.8 million (vs. $7.9 million in 2023).Current assets: $25.3 million as of December 31, 2024. Expected 2025 MilestonesPlinabulin 1H 2025: Updated data from Phase 2 of Study 303 in metastatic NSCLC progressed on PD-1/PD-L1 inhibitors.2H 2025: Preliminary data from Phase 2 of Study 302 in 1L ES-SCLC. SEED Mid-2025: Expected IND filing of RBM39 degrader.2H 2025: RBM39 degrader expected to begin patient enrollment.2H 2025: Tau degrader expected to achieve in vivo efficacy. Note: 1. As a result of BeyondSpring entering into definitive agreements to sell a portion of its Series A-1 Preferred Shares of SEED, SEED’s operations met the criteria as discontinued operations under ASC 205-20 for financial reporting purposes. About BeyondSpringBeyondSpring (NASDAQ: BYSI) is a clinical-stage biopharmaceutical company developing first-in-class therapies for high unmet medical needs. Its lead asset, Plinabulin, is in late-stage clinical development as an anti-cancer agent in NSCLC and a range of cancer indications. Plinabulin’s novel mechanism of action as a dendritic cell maturation agent supports both anti-cancer activity and immune modulation, offering a unique approach to resensitizing tumors to checkpoint inhibitors. Learn more at beyondspringpharma.com. About SEED TherapeuticsSEED Therapeutics is a biotech company pioneering targeted protein degradation (TPD). Its proprietary RITE3™ platform is advancing novel molecular glue degraders across oncology, neurodegeneration, immunology, and virology. SEED collaborates with Eli Lilly and Company and Eisai Co., Ltd. and is advancing its RBM39 degrader into clinical development. Learn more at seedtherapeutics.com. Cautionary Note Regarding Forward-Looking StatementsThis press release includes forward-looking statements that are not historical facts. Words such as “will,” “expect,” “anticipate,” “plan,” “believe,” “design,” “may,” “future,” “estimate,” “predict,” “objective,” “goal,” or variations thereof and variations of such words and similar expressions are intended to identify such forward-looking statements. Forward-looking statements are based on BeyondSpring’s current knowledge and its present beliefs and expectations regarding possible future events and are subject to risks, uncertainties, and assumptions. Actual results and the timing of events could differ materially from those anticipated in these forward-looking statements as a result of several factors including, but not limited to, difficulties raising the anticipated amount needed to finance the Company’s future operations on terms acceptable to the Company, if at all, unexpected results of clinical trials, delays or denial in regulatory approval process, results that do not meet the Company’s expectations regarding the potential safety, the ultimate efficacy or clinical utility of the Company’s product candidates, increased competition in the market, the Company’s ability to meet Nasdaq’s continued listing requirements, and other risks described in BeyondSpring’s most recent Form 10-K on file with the U.S. Securities and Exchange Commission. All forward-looking statements made herein speak only as of the date of this release and BeyondSpring undertakes no obligation to update publicly such forward-looking statements to reflect subsequent events or circumstances, except as otherwise required by law. Investor Contact: IR@beyondspringpharma.comMedia Contact: PR@beyondspringpharma.com Financial Tables to Follow BEYONDSPRING INC.CONSOLIDATED BALANCE SHEETS(Amounts in thousands of U.S. Dollars (“$”), except for number of shares and per share data) As of December 31, 2023 2024 $ $ Assets Current assets: Cash and cash equivalents 5,396 2,922 Restricted Cash 9,941 - Advances to suppliers 292 240 Prepaid expenses and other current assets 168 68 Current assets of discontinued operations 2,622 25,347 Total current assets 18,419 28,577 Noncurrent assets: Property and equipment, net 317 239 Operating right-of-use assets 730 513 Other noncurrent assets 123 213 Noncurrent assets of discontinued operations 5,219 4,773 Total noncurrent assets 6,389 5,738 Total assets 24,808 34,315 Liabilities and equity Current liabilities: Accounts payable 561 295 Accrued expenses 2,347 840 Current portion of operating lease liabilities 258 282 Other current liabilities 1,069 780 Current liabilities of discontinued operations 3,723 8,813 Total current liabilities 7,958 11,010 Noncurrent liabilities: Operating lease liabilities 589 307 Deferred revenue 28,170 27,400 Other noncurrent liabilities 3,705 3,686 Noncurrent liabilities of discontinued operations 7,847 6,197 Total noncurrent liabilities 40,311 37,590 Total liabilities 48,269 48,600 Commitments and contingencies (Note 13) Mezzanine equity Contingently redeemable noncontrolling interests – discontinued operations 11,874 - Shareholders’ deficit Ordinary shares ($0.0001 par value; 500,000,000 shares authorized; 39,029,163 and 40,316,320 shares issued and outstanding as of December 31, 2023 and 2024, respectively) 4 4 Additional paid-in capital 368,599 373,185 Accumulated deficit (396,302) (407,425)Accumulated other comprehensive income 894 1,336 Total BeyondSpring Inc.’s shareholders’ deficit (26,805) (32,900)Noncontrolling interests (8,530) 18,615 Total shareholders’ deficit (35,335) (14,285) Total liabilities, mezzanine equity and shareholders’ deficit 24,808 34,315 BEYONDSPRING INC.CONSOLIDATED STATEMENTS OF COMPREHENSIVE LOSS(Amounts in thousands of U.S. Dollars (“$”), except for number of shares and per share data) Year ended December 31, 2023 2024 $ $ Revenue - - Operating expenses Research and development (7,272) (2,644)General and administrative (7,809) (6,110) Loss from operations (15,081) (8,754)Foreign exchange loss, net (128) (96)Interest income 322 59 Other income, net 964 22 Loss before income tax (13,923) (8,769)Income tax expenses (92) (96) Net loss from continuing operations (14,015) (8,865) Discontinued operations Loss from discontinued operations (7,919) (7,828)Income tax expenses (14) - Net loss from discontinued operations (7,933) (7,828) Net loss (21,948) (16,693)Less: Net loss attributable to noncontrolling interests from continuing operations (922) (388)Less: Net loss attributable to noncontrolling interests from discontinued operations - (5,182)Net loss attributable to BeyondSpring Inc. (21,026) (11,123) Net loss per share, basic and diluted Continuing operations (0.34) (0.21)Discontinued operations (0.20) (0.07)Basic and diluted loss per share (0.54) (0.28) Weighted-average shares outstanding Basic and diluted 38,996,463 39,733,191 Other comprehensive loss, net of tax of nil: Foreign currency translation adjustment gain from continuing operations 760 710 Foreign currency translation adjustment (loss) gain from discontinued operations (35) 17 Comprehensive loss (21,223) (15,966)Less: Comprehensive loss attributable to noncontrolling interests from continuing operations (655) (131)Less: Comprehensive loss attributable to noncontrolling interests from discontinued operations - (5,154)Comprehensive loss attributable to BeyondSpring Inc. (20,568) (10,681)