Totus Medicines Presents Early Phase 1b Clinical Data Demonstrating 100% Disease Control Rate and Class-Leading Safety for TOS-358 + Fulvestrant Doublet Therapy in HR+/HER2- Breast Cancer at ESMO Breast Cancer Annual Congress 2026

TOS-358 is a covalent, pan-mutant, a-selective PI3K inhibitor designed to address key limitations of existing PI3Ka therapies which include limited mutation coverage and poor tolerability

First presentation of combination data demonstrates 100% disease control rate and 89% clinical benefit rate in women, including PAM-experienced patients, with median time on therapy exceeding 24 weeks

Poster presented May 7, at ESMO Breast Cancer Annual Congress 2026 in Berlin, Germany

EMERYVILLE, Calif., May 06, 2026 (GLOBE NEWSWIRE) -- Totus Medicines, a clinical-stage, precision medicines company leveraging AI-powered small molecule drug discovery to advance a differentiated pipeline of therapeutics against high-value, historically difficult-to-drug targets, today announced the presentation of interim Phase 1b clinical data from its ongoing study of TOS-358, a next-generation pan-mutant, covalent, alpha-selective PI3Ka inhibitor, in combination with Fulvestrant, in heavily pre-treated metastatic HR+/HER2− breast cancer patients. The data were presented at the European Society for Medical Oncology (ESMO) Breast Cancer Annual Congress, taking place in Berlin, Germany, May 5–8, 2026.

Presentation Details:

Conference: ESMO Breast Cancer 2026

Session: Poster Presentation

Abstract Number: 492P

Date / Time: 13:15, Thursday, May 7, 2026

“These initial combination data with TOS-358 and Fulvestrant are highly encouraging and reinforce our confidence in TOS-358’s differentiated profile as a covalent, pan-mutant PI3Ka inhibitor,” said Zelanna Goldberg, M.D., Chief Medical Officer of Totus Medicines. “Achieving 100% disease control and an 89% clinical benefit rate in women, including patients with prior PI3K/AKT/mTOR pathway therapy, alongside a class-leading tolerability profile, underscores the potential of TOS-358 to address a critical unmet need in HR+/HER2− metastatic breast cancer. The durability of responses, with more than 60% of patients remaining on therapy beyond 24 weeks, further validates our approach of near-total, sustained PI3Ka pathway suppression.”

First Combination Data: TOS-358 + Fulvestrant Efficacy and Durability

The poster (Abstract 492P) presents the early clinical data from the doublet cohort of TOS-358-001, the ongoing open-label, global, multi-center Phase 1 study. Ten evaluable HR+/HER2− breast cancer patients were treated with TOS-358 in combination with Fulvestrant (median 3.5 prior lines of therapy; range 1–5), with a data cutoff of March 31, 2026. Key efficacy and durability findings include:

• 100% Disease Control Rate (DCR) in women treated with TOS-358 + Fulvestrant
• 89% Clinical Benefit Rate (CBR) in women, including patients who had received prior PI3K/AKT/mTOR (PAM)-directed therapy and patients in the 4th line and beyond
• Responses continued to deepen over time, including conversions from stable disease (SD) to partial responses (PR), consistent with TOS-358’s near-total inhibition of PI3Ka signaling
• 60% of patients on TOS-358 + Fulvestrant remained on therapy beyond 24 weeks, with an additional 20% of patients ongoing at less than 24 weeks on trial; median time on therapy exceeds 24 weeks for the overall Phase 1 population
• A 72-year-old heavily pre-treated patient with an H1047K/G106V dual PI3Ka mutation achieved a confirmed RECIST partial response of ~68%, with near complete PET-CT resolution of bone metastases
  

Class-Leading Safety and Tolerability

Across the overall TOS-358 safety population to date (N=56, including monotherapy and doublet patients), TOS-358 demonstrated a class-leading tolerability profile with an absence of toxicities that have limited other PI3Ka inhibitors:

• 0% bone marrow toxicity
• 0% hepatic toxicity
• 0% renal toxicity
• 0% ocular symptoms
• 0% rash
• 0% stomatitis/mucositis
• 0% grade 3 diarrhea
• Hyperglycemia was manageable: only 3.6% of patients (2/56) required ongoing insulin, and all patients who received insulin were obese (BMI >30)
• No treatment discontinuations due to intolerance to TOS-358
  

Maturing Overall Phase 1 Experience

The overall Phase 1 cohort currently demonstrates a 78% DCR and 57% CBR, with data continuing to mature. Among the overall population treated with TOS-358, median time on therapy now exceeds 24 weeks, with 50% of patients maintaining disease control beyond this landmark. The ongoing Phase 1b expansion cohort is currently enrolling across doublet (TOS-358 + Fulvestrant) and triplet (TOS-358 + Fulvestrant + CDK4/6 inhibitor) arms.

TOS-358: A Differentiated Approach to PI3Ka Inhibition

TOS-358 is the first and only clinical-stage covalent PI3Ka inhibitor. As a pan-mutant, a-selective oral small molecule, TOS-358 achieves >95% continuous target engagement at clinically relevant doses through covalent binding to a cysteine residue equally accessible in helical, kinase-domain, and other mutants of PI3Ka while avoiding high plasma concentrations that can potentially lead to off-target effects. This broad mutant coverage - extending to acquired resistance mutations - differentiates TOS-358 from non-covalent and mutation-selective PI3Ka inhibitors currently approved or in development. The near-total, sustained suppression of oncogenic signaling enabled by this mechanism is reflected in the depth and durability of responses observed clinically, as well as the absence of many of the class-effect toxicities that have limited other agents.

PI3Ka driver mutations are present in approximately 40% of ER-positive/HER2-negative breast cancer, 50% of endometrial adenocarcinoma, and a meaningful subset of head and neck squamous cell carcinoma (HNSCC) patients. Totus Medicines is advancing TOS-358 as a potential best-in-class PI3Ka inhibitor across selected solid tumor indications. TOS-358-001 (EU CT 2023-505346-26-01; NCT#05683418) is an ongoing open-label, global, multi-center Phase 1 study evaluating the safety and efficacy of TOS-358 alone and in combination.

About Totus Medicines:

Totus Medicines is a clinical-stage, precision medicines company, discovering novel covalent small molecules against previously undrugged or difficult to drug targets, based on its proprietary AI-powered OmniDEL platform (DNA-encoded covalent library technology). The company's lead program, TOS-358, the first and only covalent PI3Ka inhibitor in clinical development, has shown efficacy, response and long-term disease control with class-leading tolerability in breast, endometrial and head & neck cancers. The company's lead pre-clinical program is targeting IRF5, a key genetically validated but previously undrugged target across multiple I&I indications. For more information, please visit www.totusmedicines.com

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