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Oral presentation of Phase 1a clinical data highlights potential best-in-class drug profile in heavily pretreated patients with PI3Kα-mutant metastatic breast cancer and other solid tumors.

Overall, TOS-358 demonstrated a 50% clinical benefit rate (CBR), 75% disease control rate (DCR), and 45% of patients remained on drug for more than 24 weeks.

67% of PI3K/AKT/mTOR (“PAM”)-resistant patients and 100% of PAM-intolerant patients achieved clinically meaningful disease control.

TOS-358 demonstrated a class-leading safety profile with no evidence of bone marrow, hepatic, ocular, or dermatologic toxicities (rash or stomatitis/mucositis), and less than 5% Grade 2 diarrhea or nausea. Hyperglycemia requiring insulin for ongoing blood glucose control was less than 4%, positioning TOS-358 well for combination therapies.

Phase 1b initiated in January 2026, exploring doublet- and triplet combinations with fulvestrant and CDK4/6 inhibitors.

EMERYVILLE, Calif., March 18, 2026 /PRNewswire/ — Totus Medicines, a clinical-stage precision medicine company leveraging a novel covalent DNA-encoded library and AI-powered small molecule drug discovery platform, today announced the presentation of new clinical data for TOS-358 at the European Society for Medical Oncology Targeted Anticancer Therapies (ESMO TAT) Congress in Paris, France.

“TOS-358 was designed to overcome the limitations of currently available PI3Kα inhibitors by delivering sustained and specific, greater than 90% covalent inhibition of the target combined with a best-in-class safety profile,” said Zelanna Goldberg, M.D., Chief Medical Officer of Totus Medicines. “We are very encouraged by the early clinical efficacy data, which demonstrate durable tumor control and class-leading tolerability in heavily pretreated patients.”

“TOS-358 is among the most interesting agents in this class to emerge. It appears to be a well-tolerated and straightforward drug to administer for PI3Kα mutant disease, with early data suggesting the potential for meaningfully durable tumor control,” said Dr. Antonio Giordano.

TOS-358 is an oral, highly selective, pan-mutant, covalent PI3Kα inhibitor that achieves greater than 95% continuous target engagement for deep and durable inhibition of PI3K-AKT signaling.

Phase 1a Key Clinical Findings

Clinical results from the efficacy cohort demonstrated encouraging anti-tumor activity and durability of response.

Overall efficacy profile:

CBR: 50%
DCR: 75%
ORR: 15%
≥20% tumor shrinkage: 40%
Patients on therapy for ≥24 weeks: 45%

Clinically meaningful disease control in heavily pre-treated patients:

DCR in PAM-resistant patients: 67%
DCR in PAM-intolerant patients: 100%

Class-leading Safety and Tolerability Profile

TOS-358 demonstrated a favorable and differentiated safety profile with minimal gastrointestinal or epithelial toxicities.

Key observations:

No bone marrow toxicity
No hepatic toxicity
No renal toxicity
No ocular symptoms
No rash
No stomatitis or mucositis
Less than 5% of patients required medication for nausea or diarrhea

Hyperglycemia, an expected on-target effect of PI3Kα inhibition, was primarily low grade and manageable with oral medications. Only 3.6% (2/54 patients) required ongoing insulin.

Phase 1b Study Design

TOS-358 is currently being evaluated in an ongoing Phase 1b study to assess safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity in combination with fulvestrant and CDK4/6 inhibitors in patients with PI3Kα-mutated HR+/HER2- metastatic breast cancer.

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 using its proprietary AI-powered OmniDEL platform.

The company’s lead program, TOS-358, is the first and only covalent PI3Kα inhibitor in clinical development and has demonstrated efficacy, response, and long-term disease control with strong tolerability across multiple cancer types.

For more information, visit www.totusmedicines.com