Core Insights - Aptevo Therapeutics reported significant clinical progress and financial results for 2025, highlighting the potential of mipletamig in enhancing frontline AML treatment alongside standard therapies [2][3][4] Clinical Performance - Mipletamig demonstrated an 86% clinical benefit rate in combination therapy for frontline AML patients, with a 79% complete response (CR) or complete response with incomplete blood count recovery (CRi) rate, compared to 66% for standard care [5][7] - The treatment showed a 61% complete remission rate, significantly higher than the 37% observed with standard therapies [5] - No cytokine release syndrome was reported in patients treated with mipletamig, indicating a favorable safety profile [7][8] Pipeline Expansion - The company expanded its CD3 pipeline by introducing three new multispecific candidates, including its first two trispecific drug candidates, enhancing its ability to target a broader range of tumor types [4][9] - The new candidates leverage the proprietary CRIS7-derived CD3 binding domain, aimed at promoting targeted T-cell activation while minimizing systemic overstimulation [10] Financial Overview - Aptevo ended 2025 with $21.6 million in cash and cash equivalents, an increase from $8.7 million in 2024, supporting operations into the fourth quarter of 2026 [11][14] - Research and development expenses rose to $14.5 million in 2025 from $14.4 million in 2024, primarily due to increased costs associated with mipletamig [14] - General and administrative expenses increased to $11.8 million in 2025, up from $10.2 million in 2024, driven by higher employee and consulting costs [15] Capital Strategy - In 2026, Aptevo established a $60 million equity line facility to enhance financial flexibility and support ongoing operations, with the potential to extend its capital runway into 2029 if fully utilized [4][12]

Core Insights - Mipletamig demonstrates an 86% clinical benefit rate in combination with venetoclax and azacitidine for newly diagnosed acute myeloid leukemia (AML) patients, with no cases of cytokine release syndrome (CRS) reported [1][2] - The data indicates a strong efficacy profile and favorable safety, suggesting mipletamig could enhance current AML treatment standards, particularly for older or unfit patients [1][2] Clinical Data Highlights - Among 28 evaluable frontline patients, 100% remained free of CRS, with an 86% clinical benefit rate observed [1] - 79% of patients achieved complete remission (CR) or complete remission with incomplete blood marker recovery (CRi), with 61% achieving CR [1] - 55% of patients who achieved CR/CRi reached measurable residual disease-negative levels, indicating stronger responses [1] - 35% of patients with remissions had the TP53 genetic mutation, a high-risk biomarker associated with poor prognosis in AML [1] Company Overview - Aptevo Therapeutics is a clinical-stage biotechnology company focused on developing novel immunotherapies for cancer, utilizing proprietary ADAPTIR and ADAPTIR-FLEX platforms [2] - The company aims to improve treatment outcomes for cancer patients, with mipletamig being a key candidate for AML treatment [2]

Core Insights - Aptevo Therapeutics is undergoing executive leadership transitions to support its strategic objectives and growth as it advances into 2026 and beyond [1][2] Leadership Transition - Effective April 1, 2026, Marvin White will retire as President and CEO, transitioning to Executive Chair to focus on strategic opportunities [2] - Jeff Lamothe, currently Chief Operating Officer, will become the new President and CEO and join the Board of Directors [2] - John E. Niederhuber, M.D., will move from Chairman of the Board to Lead Independent Director, ensuring continuity in leadership [2] Company Progress - Aptevo has reached a significant inflection point with a clinically proven platform, a growing body of patient data, and a strong financial position [3] - The company has established proof-of-concept for its proprietary technology and expanded its pipeline to include eight molecules, including two trispecific programs [3] - More than 100 patients have been treated with the CD123 x CD3 program, mipletamig, showing strong efficacy and a differentiated safety profile in acute myeloid leukemia [3] Financial Position - Aptevo has strengthened its financial position, establishing a cash runway into 2029, including a $60 million equity line of credit [4] - The company's accomplishments reflect disciplined execution across technology development, clinical advancement, pipeline expansion, and financial stewardship [4] Leadership Confidence - Marvin White expressed confidence in Jeff Lamothe's leadership, highlighting his instrumental role in the company's key advances [6][7] - Lamothe emphasized the importance of disciplined execution and advancing the pipeline to positively impact cancer patients [8] Future Outlook - The leadership structure is aligned to support both execution and long-term strategy, positioning Aptevo to continue progressing toward its objectives [9]

As filed with the Securities and Exchange Commission on January 28, 2026 Registration No. 333- UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, D.C. 20549 FORM S-1 REGISTRATION STATEMENT UNDER THE SECURITIES ACT OF 1933 APTEVO THERAPEUTICS INC. (Exact Name of Registrant as Specified in Its Charter) (State or Other Jurisdiction of Incorporation or Organization) (Primary Standard Industrial Classification Code Number) Delaware 2834 81-1567056 (I.R.S. Employer Identification Number) 2401 4th Avenue ...

Core Insights - 100% of patients in Cohorts 1-3 remain free of cytokine release syndrome, indicating a strong safety profile for the CD3 design used in the study [1] - The study evaluates mipletamig, a CD123 x CD3 bispecific molecule, in combination with azacitidine and venetoclax for newly diagnosed acute myeloid leukemia patients unfit for intensive chemotherapy [1] - Preliminary results were presented at the American Society of Hematology Annual Meeting, highlighting the potential of the ADAPTIR™ and ADAPTIR-FLEX™ platform technologies developed by the company [1] Company Summary - Aptevo Therapeutics Inc. is a clinical-stage biotechnology company focused on developing novel immune-oncology therapeutics [1] - The company utilizes proprietary ADAPTIR™ and ADAPTIR-FLEX™ platform technologies in its research and development efforts [1] Industry Context - The ongoing Phase 1b/2 RAINIER study is significant for the treatment of acute myeloid leukemia, particularly for patients who cannot undergo intensive chemotherapy [1] - The combination of mipletamig with standard treatments like azacitidine and venetoclax represents a potential advancement in the therapeutic options available for AML [1]

Core Insights - Aptevo Therapeutics has presented preclinical data for its trispecific antibody candidate, APVO451, at the Society for Immunotherapy of Cancer Annual Meeting, highlighting its potential in treating hard-to-treat solid tumors [1][2]. Company Update - APVO451 is designed to address the challenge of immune suppression in solid tumors, such as urothelial, breast, and pancreatic cancers, by utilizing a proprietary CRIS-7-derived CD3 binding domain [2][3]. - The molecule aims to activate the intratumoral immune system, enhancing the ability to target and kill tumor cells effectively [3]. Key Findings from the Presentation - APVO451 demonstrated local activation of T-cells and antigen-presenting cells (APCs) only when bound to the target protein, nectin-4, indicating a favorable safety profile [4]. - The candidate showed dual immune re-activation by stimulating T-cell effector functions and restoring APC function, addressing a common failure point in solid tumor treatments [4]. - In tumor models simulating suppression, APVO451 was more effective in eliminating nectin-4-positive tumor cells compared to standard CD3 T-cell engagers, suggesting its potential to overcome suppressive tumor environments [4]. Next Steps - Aptevo is advancing APVO451 through ongoing preclinical studies to support IND-enabling work and future clinical development targeting nectin-4-expressing solid tumors [5]. About APVO451 - APVO451 is a trispecific ADAPTIR-FLEX therapeutic candidate designed to engage CD3 and CD40, aiming to restore immune engagement in suppressive solid tumors while minimizing off-tumor activation [6]. About Aptevo Therapeutics - Aptevo Therapeutics is a clinical-stage biotechnology company focused on developing novel bispecific and trispecific immunotherapies for cancer treatment, with two clinical candidates currently in trials [7].

Core Insights - Aptevo Therapeutics reported that 89% of evaluable frontline AML patients achieved remission in combination therapy across two trials, with a notable 100% remission rate in Cohort 3 of the ongoing RAINIER trial [1][1][1] - The company introduced its first trispecific molecules, APVO451 and APVO452, aimed at overcoming immune suppression in certain solid tumors, utilizing a unique CRIS-7-derived CD3 binding domain [1][1][1] - Aptevo's CD3 T-cell engager portfolio has been expanded to five molecules, indicating growth in its therapeutic offerings [1][1][1] - The company raised $18.7 million in the third quarter and an additional $4.1 million since the quarter ended, extending its cash runway into the fourth quarter of 2026 [1][1][1] Financial Performance - The financial results for the quarter ended September 30, 2025, were reported alongside a business update, highlighting the company's ongoing development in immune-oncology therapeutics [1][1][1]

Core Insights - Aptevo Therapeutics is actively participating in several key financial, industry, scientific, and medical conferences this fall to showcase its ongoing developments and momentum in the biotechnology sector [1] Conference Participation - Aptevo will participate in the 4th Annual ROTH Healthcare Opportunities Conference on October 9, 2025, discussing its lead asset mipletamig and its clinical progress in Acute Myeloid Leukemia (AML) [1] - The company will also be present at the Biotechnology Innovation Organization (BIO)-Europe 2025 from November 3-5, 2025, engaging in meetings at the largest biotechnology event in Europe [1] - At the Society of Immunotherapy in Cancer (SITC) 2025, scheduled for November 5-9, 2025, Aptevo's R&D team will present a poster on a novel trispecific targeting approach to address the immunosuppressive tumor microenvironment [1] - The interim results from the ongoing Phase 1b/2 RAINIER trial evaluating mipletamig in frontline combination therapy for AML will be presented at the American Society of Hematology (ASH) 2025 meeting from December 6-9, 2025 [1]

As filed with the Securities and Exchange Commission on October 1, 2025 Registration No. 333- UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, D.C. 20549 FORM S-1 REGISTRATION STATEMENT UNDER THE SECURITIES ACT OF 1933 APTEVO THERAPEUTICS INC. (Exact Name of Registrant as Specified in Its Charter) Delaware 2834 81-1567056 (State or Other Jurisdiction of Incorporation or Organization) (Primary Standard Industrial Classification Code Number) (I.R.S. Employer Identification Number) 2401 4th Avenue, ...

Core Insights - Aptevo Therapeutics Inc. (APVO) experienced a significant stock increase of 46.10% to $2.06 after reporting breakthrough clinical results for its drug aimed at treating acute myeloid leukemia (AML) [1] Clinical Trial Results - The Phase 1b/2 RAINIER trial showed a perfect remission rate, with all patients in Cohort 3 achieving complete remission using mipletamig in combination with venetoclax and azacitidine [2] - No dose-limiting toxicities or cytokine release syndrome were reported across all cohorts of the trial, indicating a favorable safety profile [2] Market Opportunity and Future Steps - The frontline AML market represents a multi-billion-dollar opportunity, with current standard treatments yielding lower remission rates compared to those observed in the RAINIER trial [3] - 40% of patients in the trial achieved minimal residual disease-negative status, which is a positive indicator for prognosis [3] - Enrollment for Cohort 4 is ongoing at higher dose levels, with a conference presentation anticipated in the fourth quarter [3] Stock Performance Overview - APVO's stock has seen a decline of approximately 31.9% from its one-month peak of $2.07 to a close of $1.41 [4] - Over the past year, the stock has decreased by 98.84%, and it is down 98.36% year-to-date in 2025 [4] - The clinical-stage stock has an annual trading range between $1.32 and $381.10, with a market capitalization of $4.64 million and an average trading volume of 3.98 million shares [4]