Integrated analyses show higher tumor exposure than doxorubicin and better preservation of cardiac function in randomized soft tissue sarcoma studies despite approximately 3.5-fold higher cumulative doxorubicin-equivalent exposure
SAN FRANCISCO--(BUSINESS WIRE)--#ASCO--Gemini Therapeutics, Inc., a privately held biotechnology company focused on advancing aldoxorubicin for patients with cancer, today announced two aldoxorubicin abstracts at the 2026 American Society of Clinical Oncology Annual Meeting. The analyses examine complementary elements of aldoxorubicin’s development rationale: tumor-targeted anthracycline delivery and cardiac safety at cumulative doxorubicin-equivalent exposures that are difficult to achieve with conventional doxorubicin.
Aldoxorubicin is an investigational albumin-binding prodrug of doxorubicin designed to bind endogenous albumin after intravenous administration, limit freely circulating doxorubicin, and release native doxorubicin in acidic tumor-associated and intracellular compartments. This exposure profile is intended to exploit albumin transport into tumors while reducing systemic exposure patterns associated with conventional doxorubicin, including exposure to cardiotoxic metabolites such as doxorubicinol.
“Doxorubicin remains one of oncology’s most important cytotoxic therapies, but its use is constrained by tumor-delivery limitations and cumulative cardiotoxicity,” said Diego Rey, PhD, Chief Executive Officer of Gemini Therapeutics. “These ASCO analyses support a focused re-evaluation of aldoxorubicin from two complementary directions: higher tumor exposure than conventional doxorubicin and better preservation of cardiac function despite substantially higher cumulative doxorubicin-equivalent exposure. The lower systemic doxorubicinol burden provides an important mechanistic bridge between aldoxorubicin’s albumin-bound design and the cardiac-safety findings observed in randomized soft tissue sarcoma studies. Together, these findings support the rationale that a better exposure-toxicity tradeoff could make meaningful anthracycline exposure feasible for more patients and in more tumor settings where conventional doxorubicin has been limited by delivery or cumulative cardiotoxicity.”
The first ASCO analysis, a poster presentation titled “Cardiac safety of aldoxorubicin compared to doxorubicin: Integrated results from two randomized studies in advanced soft tissue sarcoma,” evaluated cardiac safety across two randomized soft tissue sarcoma studies. The pooled analysis included 383 patients in the aldoxorubicin-versus-doxorubicin cardiac safety population: 296 treated with aldoxorubicin and 87 treated with doxorubicin comparator.
In the analysis, patients treated with aldoxorubicin received approximately 3.5-fold higher cumulative doxorubicin-equivalent exposure than patients treated with doxorubicin. Despite this higher exposure, aldoxorubicin was associated with smaller mean declines in left ventricular ejection fraction, fewer patients reaching selected on-treatment LVEF thresholds, and fewer prespecified heart-failure-related treatment-emergent adverse events.
Mechanistically, the cardiac-safety findings are supported by pharmacokinetic data showing that aldoxorubicin plasma exposure is dominated by albumin-bound doxorubicin, with substantially lower free doxorubicin and doxorubicinol concentrations. In Phase 1 aldoxorubicin data, the doxorubicinol-to-free-doxorubicin exposure ratio was approximately 5% to 6%, compared with approximately 40% to 60% reported for conventional doxorubicin, consistent with lower systemic exposure to this cardiotoxic metabolite.
Lowest on-treatment mean LVEF change from baseline was -3.17 percentage points with aldoxorubicin versus -5.77 percentage points with doxorubicin. On-treatment LVEF below 50% occurred in 3.8% of aldoxorubicin-treated patients versus 9.0% of doxorubicin-treated patients; on-treatment LVEF below 45% occurred in 1.1% versus 3.8%, respectively. Prespecified heart-failure-related treatment-emergent adverse events occurred in 3.0% of aldoxorubicin-treated patients versus 6.9% of doxorubicin-treated patients.
The second ASCO analysis, titled “Tumor Delivery and Exposure of Aldoxorubicin Compared with Doxorubicin: Integrated Clinical and Preclinical Analysis,” evaluated human tumor-biopsy pharmacokinetic data and preclinical biodistribution data comparing aldoxorubicin with doxorubicin. In human Kaposi’s sarcoma tumor biopsies, aldoxorubicin was detected in all sampled lesions and increased with dose. When normalized for dose and adjusted for potency, aldoxorubicin delivered up to approximately 10-fold higher intratumoral doxorubicin-equivalent exposure than conventional doxorubicin.
Aldoxorubicin has previously been evaluated across a broad clinical development and early access program involving more than 750 aldoxorubicin-exposed patients. Gemini acquired the aldoxorubicin program from LadRx Corporation in 2025 and is advancing it under a focused, evidence-guided development strategy informed by the substantial clinical, pharmacokinetic, and safety data generated to date.
ASCO 2026 Abstract Details
Poster Presentation
Abstract #: 11565
Poster Board #: 355
Date and Time: June 1, 2026, 1:30 PM-4:30 PM CDT
Title: Cardiac safety of aldoxorubicin compared to doxorubicin: Integrated results from two randomized studies in advanced soft tissue sarcoma
First Author: Philip Sager, MD
Presenter: Diego Rey, PhD
Citation: J Clin Oncol 44, 2026 (suppl 16; abstr 11565)
DOI: 10.1200/JCO.2026.44.16_suppl.11565
Publication Only Abstract
Abstract #: e15134
Title: Tumor delivery and exposure of aldoxorubicin compared with doxorubicin: Integrated clinical and preclinical analysis
First Author: Joyce James, PhD
Citation: J Clin Oncol 44, 2026 (suppl 16; abstr e15134)
DOI: 10.1200/JCO.2026.44.16_suppl.e15134
About Aldoxorubicin
Aldoxorubicin, also known historically as INNO-206 or DOXO-EMCH, is an investigational albumin-binding prodrug of doxorubicin. Aldoxorubicin is designed to bind endogenous serum albumin after intravenous administration and release native doxorubicin under acidic conditions found in tumor-associated and intracellular compartments. The intended therapeutic rationale is to alter the exposure pattern of doxorubicin by increasing tumor-directed anthracycline delivery while reducing systemic exposure patterns associated with conventional doxorubicin.
Aldoxorubicin is investigational and has not been approved by the U.S. Food and Drug Administration. Safety and effectiveness have not been established.
About Gemini Therapeutics
Gemini Therapeutics is a newly formed privately held biotechnology company focused on advancing aldoxorubicin for patients with cancer. Gemini was founded with a patient-centered mission to develop therapies that preserve the anti-cancer potential of foundational oncology drugs while addressing the limitations that prevent patients from receiving or continuing those therapies. The company is focused on evidence-guided development strategies in settings where aldoxorubicin’s tumor-delivery and usable anthracycline-exposure profile may matter most.
Forward-Looking Statements
This press release contains forward-looking statements, including statements regarding the potential development rationale, potential clinical utility, future development plans, regulatory strategy, and possible benefits of aldoxorubicin. These statements are based on Gemini Therapeutics’ current expectations and involve risks and uncertainties that could cause actual results to differ materially. Aldoxorubicin is investigational, and no regulatory authority has approved aldoxorubicin for any indication. The results described in prior or integrated analyses may not predict results in future studies. Gemini Therapeutics undertakes no obligation to update forward-looking statements except as required by applicable law.
Contacts
Gemini Therapeutics, Inc.
info@geminithera.com
www.geminithera.com
