TT125-802 / TOLREMO Therap - LARVOL DELTA

TOLREMO therapeutics Completes First In Human Dose Escalation for TT125-802 and Presents Solid Tumor Monotherapy Results at ESMO 2025 (GlobeNewswire) - "In the now completed dose escalation part of the study, 34 heavily pre-treated solid tumor patients received TT125-802 across 5 dose escalation cohorts (15 mg QD – 60 mg BID) and 2 cohorts examining the role of food on exposures. No MTD was reached and TT125-802 was safe and well tolerated...The EGFRmut and KRAS-G12Cmut patients had progressed on an EGFR inhibitor and KRAS-G12C inhibitor, respectively, in a prior line of therapy. Both had a rapid PR after 6 weeks of TT125-802 monotherapy and remained progression-free for almost 7 months. The squamous NSCLC patient had progressed on standard-of-care therapy and had a PR after 12 weeks of TT125-802. The patient was on study for 5.5 months until progression."

P1 data • Lung Non-Squamous Non-Small Cell Cancer

Clinical activity of TT125-802, a highly selective bromodomain inhibitor of CBP/p300, in advanced solid tumors: Update on the ongoing phase I study (ESMO 2025) - "TT125-802 was well-tolerated with a best-in-class safety profile, without thrombocytopenia, compared to other CBP/p300 inhibitors. Further development will focus on combination strategies with KRAS and EGFR inhibitors in NSCLC."

Clinical • Metastases • P1 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS

TOLREMO therapeutics Welcomes Multiple Myeloma Leader Kenneth C. Anderson to its Scientific Advisory Board (GlobeNewswire) - "His unparalleled expertise in translational and clinical research in multiple myeloma will guide TOLREMO as it expands the clinical development program for its lead candidate TT125-802 beyond solid tumors and into hematologic malignancies."

Clinical • Hematological Malignancies • Solid Tumor

TOLREMO therapeutics Receives Two FDA Fast Track Designations for TT125-802 in Pretreated, Advanced or Metastatic NSCLC With Either an EGFR or a KRAS-G12C Mutation (The Manila Times) - "One Fast Track designation was granted for the treatment of patients with locally advanced or metastatic NSCLC with an epidermal growth factor receptor (EGFR) exon 19 deletion or exon 21 L858R substitution mutation, with disease progression on at least one line of prior therapy including an EGFR inhibitor. The second Fast Track designation was granted for the treatment of patients with locally advanced or metastatic kirstin rat sarcoma viral oncogene homolog (KRAS)-G12C mutated NSCLC, with disease progression on at least one line of prior therapy including a KRAS G12C inhibitor."

Evidence highlight • Fast track • Non Small Cell Lung Cancer • EGFR • KRAS

TT125-802, a highly selective, well-tolerated bromodomain inhibitor of CBP/p300 with anti-tumor activity in patients with advanced solid tumors: An update on the ongoing phase I study. (ASCO 2025) - P1 | "TT125-802 has a well tolerated and differentiated safety profile from other CBP/p300 targeting drugs with no thrombocytopenia and has shown encouraging signs of anti-tumor activity in advanced solid tumors. Updated clinical data, including food effect on drug exposure, additional dose cohorts, PK/PD, and ctDNA changes will be presented at the meeting."

Clinical • Metastases • P1 data • Adenoid Cystic Carcinoma • Ampulla of Vater Carcinoma • Anal Carcinoma • Anemia • Breast Cancer • Castration-Resistant Prostate Cancer • Dental Disorders • Diabetes • Fatigue • Liposarcoma • Lung Cancer • Non Small Cell Lung Cancer • NUT Midline Carcinoma • Oncology • Prostate Cancer • Sarcoma • Solid Tumor • Stomatitis • Thrombocytopenia • Thymus Cancer

TOLREMO therapeutics Announces TT125-802 is the First CBP/p300 Bromodomain Inhibitor to Show Clinical Activity in Solid Tumors (The Manila Times) - P1 | N=50 | TT-CSP-001 (NCT06403436) | Sponsor: TOLREMO therapeutics AG | "TOLREMO therapeutics AG...announced data from its ongoing Phase I study of TT125-802, a novel, orally administered bromodomain inhibitor of CBP/p300, for patients with advanced solid tumors who have relapsed or are refractory to standard-of-care therapies, including an abstract published at the 2025 American Society of Clinical Oncology (ASCO) annual meeting. To date TT125-802 shows impressive anti-tumor activity in advanced solid tumors, including deep and durable responses in non-small cell lung cancer (NSCLC). In addition, TT125-802 demonstrates a best-in-class safety profile without thrombocytopenia, the primary toxicity associated with its class of inhibitors."

P1 data • Non Small Cell Lung Cancer

TT-CSP-001: A Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Efficacy of TT125-802 in Subjects With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=50 | Recruiting | Sponsor: TOLREMO therapeutics AG | Trial completion date: Dec 2025 ➔ Dec 2026 | Trial primary completion date: Jul 2025 ➔ Aug 2026

Trial completion date • Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Preclinical development and characterization of IACS-16559, a dual bromodomain inhibitor of CBP/EP300, and its potential in AML subtypes (AACR 2025) - "Clinical validation of bromodomain inhibition of paralogs CBP and EP300 is undergoing in multiple clinical trials, including both hematological diseases and solid tumors, using EP31670, CCS1477 and TT125-802, while selective CBP or EP300 inhibition is being explored preclinically. However, in contrast, long-term treatment in the MLL-AF9 (MOLM14) model resulted in antagonistic effects. These findings underscore the complexities of combinatorial therapeutic development and emphasize the critical need for careful selection of robust therapeutic combinations and consideration of the genetic background in the target disease."

Preclinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • Solid Tumor • BRD4 • EP300

TT125-802, a highly selective bromodomain inhibitor of CBP/p300, in patients with advanced solid tumors: an update on the phase I study (EORTC-NCI-AACR 2024) - P1 | "Preliminary clinical data from TT125-802 demonstrate a generally well tolerated safety profile. Despite heavily pre-treated patients with solid tumors, encouraging signals of reduction/stabilization of disease burden by TT125-802 have been observed. Updated clinical data, including additional dose cohorts and PK/PD, will be presented at the meeting."

Clinical • Metastases • P1 data • Adenoid Cystic Carcinoma • Anal Carcinoma • Breast Cancer • Gastrointestinal Cancer • Liposarcoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Sarcoma • Solid Tumor • Thymoma • Thymus Cancer

A phase 1, first-in-human, open-label study evaluating the safety, tolerability, pharmacokinetics, and efficacy of TT125-802 in patients with advanced solid tumors. (ASCO 2024) - "6. AACR2023 poster #3907."

Clinical • Metastases • P1 data • PK/PD data • Castration-Resistant Prostate Cancer • Colorectal Cancer • Genito-urinary Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Prostate Cancer • Solid Tumor • KRAS

TT-CSP-001: A Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Efficacy of TT125-802 in Subjects With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=50 | Recruiting | Sponsor: TOLREMO therapeutics AG

Metastases • New P1 trial • Oncology • Solid Tumor

An image-based phenotypic screen identified CBP/p300 as new cancer drug resistance target and enabled the development of the clinical candidate TT125-802 (AACR 2024) - "Validating our phenotypic approach to drug discovery and development, TT125-802 is currently being evaluated in a phase I oncology trial. The modular setup of our phenotypic screening system has the potential to power the discovery of additional novel modulators of transcriptional drug resistance."

Clinical • Melanoma • Oncology • Solid Tumor • BRD2 • BRD4 • ITK • SOX2

TOLREMO Treats First Patient in Phase I Trial with TT125-802, a Novel Therapeutic Agent to Overcome Transcriptional Cancer Drug Resistance (Businesswire) - "TOLREMO therapeutics AG...announced that the first patient has been dosed in its first-in-human clinical trial evaluating the safety and tolerability, pharmacokinetics, and pharmacodynamics of its lead candidate, TT125-802, in patients across a range of solid tumor indications....The Phase I dose-escalation study will enroll patients across a range of solid tumor indications."

Trial status • Oncology • Solid Tumor

TOLREMO therapeutics Completes USD 39 Million Series A Financing Round with Strategic Investment from Pierre Fabre Invest (Businesswire) - "TOLREMO therapeutics AG...announced that it has completed its Series A financing, bringing the total amount raised to USD 39 million (CHF 34.1 million). BioMedPartners AG led the round with participation from a new investor, Pierre Fabre Invest, as well as existing investors...The proceeds of the Series A round will support the initiation of a Phase 1 monotherapy dose escalation study evaluating the safety, pharmacokinetics, pharmacodynamics, and early signs of efficacy, including biological activity of TT125-802, in a range of solid tumor indications. Stepwise, TOLREMO will then advance to evaluating TT125-802 in combination with targeted therapies such as KRAS, EGFR or AR inhibitors in specific advanced solid tumor indications."

Financing • New P1 trial • Solid Tumor

TT125-802 is a potent and highly selective CBP/p300 bromodomain inhibitor for the treatment of castration resistant prostate cancer and haematological malignancies (AACR 2023) - "In addition, preclinical studies in CRPC patient-derived xenograft (PDX)-bearing mice showed that the combination treatment of TT125-802 and enzalutamide had a synergistic effect on tumor growth inhibition compared to single agent treatments. It has therapeutic potential as monotherapy in prostate cancer and multiple myeloma and in combination with next-generation AR inhibitors for patients with lethal prostate cancer. A FIH study of TT125-802 in cancer patients is on track to start in 2023."

Genito-urinary Cancer • Hematological Malignancies • Multiple Myeloma • Oncology • Prostate Cancer • Solid Tumor • AR • CREBBP • IRF4 • KLK2 • KLK3 • TMPRSS2

Targeting adaptive resistance to EGFR and KRAS G12C inhibitors by TT125-802, a novel and specific CBP/p300 bromodomain inhibitor (AACR 2023) - "TT125-802 dose-dependently prevented osimertinib resistance development in EGFR-mutated NSCLC cell lines HCC827 and HCC4006, as well as sotorasib resistance development in KRAS G12C-mutated NCI-H358 (NSCLC), SW837 and SNU-1411 (CRCs) as assessed by label-free long-term live microscopy assays. Complementary and longitudinal analysis of transcriptional changes using RNA sequencing in vitro and in vivo identified several early adaptive and late acquired resistance signatures that were reversed by TT125-802. A first-in-human study of TT125-802 in cancer patients is on track to start in 2023."

Colorectal Cancer • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR • KRAS • SOX2 • YBX1