FOG-001 / Parabilis Medicines - LARVOL DELTA

A phase 1/2 trial of FOG-001, a first-in-class direct β-catenin:TCF4 inhibitor: safety and preliminary antitumor activity in adamantinomatous craniopharyngioma (ACP) patients (WFNOS 2025) - P1/2 | "FOG-001 has been well tolerated in patients with locally-advanced ACP. All patients have had tumor size reductions, including one PR, suggesting that the Wnt-signaling pathway is an actionable target in ACP."

Clinical • P1/2 data • Brain Cancer • Cardiovascular • CNS Tumor • Heart Failure • Hematological Disorders • Oncology • Solid Tumor • Thrombocytopenia • CTNNB1 • TCF4

A phase 1/2 trial of FOG-001, a first-in-class direct β-catenin:TCF4 inhibitor: safety and preliminary antitumor activity in adamantinomatous craniopharyngioma (ACP) patients (WFNOS 2025) - P1/2 | "FOG-001 has been well tolerated in patients with locally-advanced ACP. All patients have had tumor size reductions, including one PR, suggesting that the Wnt-signaling pathway is an actionable target in ACP."

Clinical • P1/2 data • Brain Cancer • Cardiovascular • CNS Tumor • Heart Failure • Hematological Disorders • Oncology • Solid Tumor • Thrombocytopenia • CTNNB1 • TCF4

Discovery of Helicon Peptides for the Selective Degradation of the Agonist-Bound Conformation of Androgen Receptor (ARon) in Prostate Cancer (PCF 2025) - "Background : Stabilized helical peptides (Helicons™) have been demonstrated to bind to intracellular targets at binding sites on proteins that are generally regarded as undruggable e.g., FOG-001 inhibits the b-catenin-TCF4 interaction and is currently being evaluated in the clinic in advanced solid tumors...Indeed, combination with standard-of-care inhibitors such as enzalutamide revealed additive anti-proliferative effects, likely stemming from a more comprehensive blockade of both ARON and AROFF pools. These findings demonstrate that selective degradation of the AR ON pool has the potential to provide a mechanistically novel and therapeutically promising strategy to suppress AR-dependent tumorigenesis across androgen states, including models of castration resistance. Funding Acknowledgements: No external grant funding was obtained to carry out this work Conflicts of Interest Disclosure Statement: All authors are employees of Parabilis Medicines Inc."

Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • AR • TCF4

A phase 1/2 trial of FOG-001, a first-in-class direct β-catenin:TCF4 inhibitor, preliminary safety and efficacy in patients with solid tumors bearing Wnt pathway-activating mutations (WPAM+) (AACR-NCI-EORTC 2025) - P1/2 | "When co-administered with 5-fluorouracil (5-FU), or inhibitors of VEGF or PD-1, FOG-001 showed additive to synergistic efficacy in PDX models...Pts with MSS CRC should have received prior 5-FU, oxaliplatin, and irinotecan in the metastatic setting... FOG-001 monotherapy is well tolerated with a manageable safety profile in pts with desmoid, other WPAM+ tumors and heavily pre-treated MSS CRC. Favorable PK, on-target PD effect, and encouraging anti-tumor activity demonstrate that FOG-001 is a bona fide β-catenin inhibitor with biologic and clinical impact supporting ongoing expansion in desmoid tumors, and evaluation in combination with standard chemotherapy or nivolumab in MSS CRC."

Clinical • IO biomarker • P1/2 data • Colorectal Cancer • Desmoid Tumors • Oncology • Sarcoma • Solid Tumor • CTNNB1 • TCF4

A phase 1/2 trial of FOG-001, a first-in-class direct β-catenin:TCF4 inhibitor, preliminary safety and efficacy in patients with solid tumors bearing Wnt pathway-activating mutations (WPAM+) (AACR-NCI-EORTC 2025) - P1/2 | "When co-administered with 5-fluorouracil (5-FU), or inhibitors of VEGF or PD-1, FOG-001 showed additive to synergistic efficacy in PDX models...Pts with MSS CRC should have received prior 5-FU, oxaliplatin, and irinotecan in the metastatic setting... FOG-001 monotherapy is well tolerated with a manageable safety profile in pts with desmoid, other WPAM+ tumors and heavily pre-treated MSS CRC. Favorable PK, on-target PD effect, and encouraging anti-tumor activity demonstrate that FOG-001 is a bona fide β-catenin inhibitor with biologic and clinical impact supporting ongoing expansion in desmoid tumors, and evaluation in combination with standard chemotherapy or nivolumab in MSS CRC."

Clinical • IO biomarker • P1/2 data • Colorectal Cancer • Desmoid Tumors • Oncology • Sarcoma • Solid Tumor • CTNNB1 • TCF4

Discovery of Helicon Peptides for the Selective Degradation of the Agonist-Bound Conformation of Androgen Receptor (ARON) in Prostate Cancer (AACR-NCI-EORTC 2025) - "Stabilized helical peptides (Helicons™) have been demonstrated to bind to intracellular targets at binding sites on proteins that are generally regarded as undruggable e.g., FOG-001 inhibits the b-catenin-TCF4 interaction and is currently being evaluated in the clinic in advanced solid tumors. Indeed, combination with standard-of-care inhibitors such as enzalutamide revealed additive anti-proliferative effects, likely stemming from a more comprehensive blockade of both AROFF and ARON pools. These findings demonstrate that selective degradation of the ARON pool has the potential to provide a mechanistically novel and therapeutically promising strategy to suppress AR-dependent tumorigenesis across androgen states, including models of castration resistance."

Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • AR • TCF4

A phase I/II trial of FOG-001, a first-in-class direct β-catenin:TCF4 inhibitor - Safety and preliminary antitumor activity in patients with desmoid tumors (ESMO 2025) - P1/2 | "Clinical trial identification NCT05919264. Tumor reductions were seen in all pts, including a PR in a pt who progressed on prior nirogacestat. Dose expansion in a desmoid-specific cohort is currently ongoing."

Clinical • P1/2 data • Colorectal Cancer • Desmoid Tumors • Oncology • Sarcoma • APC • CTNNB1 • TCF4

Distinct aspects of β-catenin biology drive multiple biologically rational FOG-001 combinations for MSS colorectal cancer (AACR-NCI-EORTC 2025) - P1/2 | "RAS pathway inhibition in combination with FOG-001 resulted in improved tumor growth inhibition when compared to single agent activities in CRC PDX models. Several of these combination approaches are now being tested in ongoing clinical studies of FOG-001."

IO biomarker • Colorectal Cancer • Oncology • Solid Tumor • CTNNB1 • CXCL9 • IFNG • PD-L1

Degradation of the ETS transcription factor ERG by stabilized helical peptide (Helicon™) degraders enables pharmacological validation in ERG-fusion prostate cancer models. (AACR-NCI-EORTC 2025) - P1/2 | "This platform has already yielded FOG-001, a β-catenin–TCF4 inhibitor currently in a Phase 1/2 trial (NCT05919264)...Further investigations will assess whether ERG-degrader Helicons, alone or with PRC2 inhibitors, could serve as frontline therapy for hormone-sensitive prostate cancer patients before initiating androgen deprivation treatment (ADT). These findings establish pharmacological proof of concept for ERG as a therapeutic target and support further study in prostate cancer patients."

Preclinical • Genito-urinary Cancer • Hormone Sensitive Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor • AR • CTNNB1 • ERG • MAT2A • MYC • TCF4 • TMPRSS2

Parabilis Medicines Presents Clinical Data Demonstrating First-Ever Drugging of Key Cancer Driver with FOG-001 (Businesswire) - "Oral presentation at ESMO 2025:...Of the 10 patients who had at least one post-baseline scan, tumor reductions were observed at all dose levels with a 100% disease-control rate (DCR). Of the five patients with more than one post-baseline scan, an objective response rate (ORR) of 80% (4/5) was observed....Additional presentations at AACR-NCI-EORTC, PCF, CTOS, and SNO will expand on FOG-001’s potential across a range of rare and common Wnt/β-catenin-driven solid tumors."

P1/2 data • Desmoid Tumors • Solid Tumor

Discovery of FOG-001, a clinical stage Helicon inhibitor of the beta-catenin/TCF4 interaction (ACS-Fall 2025) - P1/2 | "FOG-001 drives tumor regressions in multiple patient-derived xenograft models with Wnt pathway activating mutations at well-tolerated doses. FOG-001 is currently in a phase 1/2 clinical trial (NCT05919264)."

Clinical • IO biomarker • Colorectal Cancer • Solid Tumor • CTNNB1 • MYC • TCF4

FOG-001 - a first-in-class direct _-catenin:TCF inhibitor, in patients (pts) with colorectal cancer (CRC) and other locally advanced or metastatic solid tumors: phase 1/2 study design [WITHDRAWN] (ESMO-GI 2025) - No abstract available

Clinical • Metastases • P1/2 data • Colorectal Cancer • Oncology • Solid Tumor

A phase 1/2 study of FOG-001, a first-in-class direct β-catenin: TCF inhibitor, in patients with colorectal cancer (CRC) and other locally advanced or metastatic solid tumors. (ASCO 2025) - P1/2 | "Combination cohorts will evaluate FOG-001 + FOLFOX/bevacizumab (1L MSS CRC), FOG-001 + nivolumab (3L MSS CRC or anti-PD-1/PD-L1-resistant CRC and solid tumors), and FOG-001 + trifluridine/tipiracil + bevacizumab (3L MSS CRC)...Secondary endpoints are PK, PD, recommended phase 2 dose and schedule, and preliminary anti-tumor activity (e.g., ctDNA changes, overall response rate, best objective response, duration of response, and progression-free survival). 156 patients are planned to be enrolled in Part 1, which is currently enrolling in the USA."

Clinical • IO biomarker • Metastases • P1/2 data • Colorectal Cancer • Oncology • Solid Tumor • APC • CTNNB1

Parabilis Medicines to Present Overview of Ongoing Phase 1/2 Study of FOG-001, a β-cateninTCF4 Inhibitor, at Upcoming Medical Meetings (Businesswire) - "Parabilis Medicines...announced the presentations of trial-in-progress posters on the Company’s first-in-human clinical trial evaluating FOG-001, the first and only direct inhibitor of β-cateninTCF4, at the ASCO Annual Meeting...and the ESMO Gastrointestinal Cancers Congress 2025....FOG-001 is being evaluated in a Phase 1/2 trial (NCT05919264). The multicenter, open-label, non-randomized trial aims to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and antitumor activity of FOG-001 in patients with solid tumors with Wnt pathway activating mutations (WPAM+), including colorectal cancer (CRC) and desmoid tumors. More than 65 patients with locally advanced or metastatic tumors have been dosed with FOG-001 to date, and early clinical data demonstrate monotherapy antitumor activity and in-tumor target engagement. Phase 1/2 data are expected to be shared publicly in 2025."

P1/2 data • Trial status • Colorectal Cancer • Desmoid Tumors

Degradation of the ETS transcription factor ERG by stabilized helical peptide (Helicon™) degraders enables pharmacological validation in ERG-fusion prostate cancer models (AACR 2025) - P1/2 | "An example Helicon™ is our inhibitor of the β-catenin-TCF4 interaction, FOG-001, which is currently being evaluated in a Ph1/2 clinical trial (NCT05919264)...Collectively these data demonstrate preclinical proof of concept for this therapeutic target and mechanism of action. Ongoing optimization of these Helicons™ may allow clinical application of ERG degraders in a patient population with high unmet need."

Preclinical • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • AR • CTNNB1 • ERG • MAT2A • TCF4 • TMPRSS2

Phase 1/2 study of FOG-001, a first-in-class direct β-catenin:TCF inhibitor, in patients with colorectal cancer, hepatocellular carcinoma, and other locally advanced or metastatic solid tumors. (ASCO-GI 2025) - P1/2 | "Upon selection of the preliminary recommended Phase 2 dose from Part 1a for weekly dosing, combination dose escalation (1d) evaluates the safety/tolerability, PK and anti-tumor effects of FOG-001 in CRC patients combined with FOLFOX+bevacizumab, anti-PD-1/PD-L1 (also includes other solid tumors with known WPAM), or trifluridine/tipiracil+bevacizumab...Secondary endpoints are PK, PD, and other anti-tumor responses (e.g., best objective response, duration of response, and progression free survival). Enrollment in Parts 1 and 2 is ongoing in the USA."

Clinical • IO biomarker • Metastases • P1/2 data • Colorectal Cancer • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor • CTNNB1

Parabilis Medicines to Present Trial-in-Progress Poster on Phase 1/2 Study of FOG-001, a β-cateninTCF4 Inhibitor, at ASCO Gastrointestinal Cancers Symposium (Businesswire) - "Parabilis Medicines...announced the presentation of a trial-in-progress poster on the Company’s first-in-human clinical trial evaluating FOG-001...at the American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium taking place in San Francisco from January 23-25, 2025....FOG-001 is being evaluated in a Phase 1/2 clinical trial (NCT05919264). The multicenter, open-label, non-randomized trial aims to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and antitumor activity of FOG-001 in patients with microsatellite stable colorectal cancer (MSS CRC) and other solid tumors with Wnt pathway activating mutations (WPAM+). The trial plans to enroll patients in multiple third-line MSS CRC cohorts as both a monotherapy and in combination with FOLFOX+bevacizumab, anti-PD-1/PD-L1, or trifluridine/tipiracil+bevacizumab....Preliminary Phase 1/2 data are expected to be shared publicly in 2025."

P1/2 data • Trial status • Colorectal Cancer

FOG-001-101: FOG-001 in Locally Advanced or Metastatic Solid Tumors (clinicaltrials.gov) - P1/2 | N=480 | Recruiting | Sponsor: Parabilis Medicines, Inc. | N=245 ➔ 480

Enrollment change • Metastases • Brain Cancer • Castration-Resistant Prostate Cancer • CNS Tumor • Colorectal Cancer • Endometrial Cancer • Gastric Cancer • Genito-urinary Cancer • Hepatocellular Cancer • Lung Cancer • Microsatellite Instability • Non Small Cell Lung Cancer • Oncology • Prostate Cancer • Solid Tumor • CTNNB1 • MSI

nference Establishes AI Research Partnership with Parabilis Medicines in Colorectal Cancer (Businesswire) - "nference today announced a strategic research and data science partnership with Parabilis Medicines, Inc...focused on supporting the clinical development of Parabilis’ lead program, FOG-001, in colorectal cancer. This collaboration will provide Parabilis’ researchers with access to a vast repository of longitudinal, multimodal clinical data from millions of cancer patients sourced from top-tier medical institutions....The platform will help to accurately identify and characterize real world outcomes in patient cohorts that could benefit from Parabilis’ lead program, FOG-001, a beta-catenin inhibitor which is being investigated in a Phase 1/2 clinical trial for colorectal cancer, one of the most prevalent and challenging cancers worldwide."

Commercial • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

A first-in-human, phase 1/2 trial of FOG-001, a β-catenin:TCF antagonist, in patients with locally advanced or metastatic solid tumors. (ASCO 2024) - P1/2 | "Secondary endpoints are PK, PD, and additional antitumor activity assessments. Enrollment in Part 1 is ongoing."

Clinical • Metastases • P1/2 data • Colorectal Cancer • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CTNNB1

FogPharma Announces $145 Million Financing to Support Ongoing Clinical Development of FOG-001 and Accelerate Helicon Peptide Portfolio (Businesswire) - "FogPharma...announced the successful closing of a $145 million Series E financing round. The financing was led by Nextech Invest with participation from other new investors including RA Capital Management, Rock Springs Capital, General Catalyst, Marshall Wace, Samsara Biocapital, Foresite Capital, Symbiosis, Catalio Capital Management, Sixty Degree Capital and former chairman and CEO of Johnson & Johnson, Alex Gorsky....The financing will fund the ongoing clinical development of FOG-001, the company’s first-in-class intracellular TCF-blocking β-catenin inhibitor currently being evaluated in a Phase 1/2 study in solid tumors."

Financing • Oncology • Solid Tumor

FOG-001 in Locally Advanced or Metastatic Solid Tumors (clinicaltrials.gov) - P1/2 | N=208 | Recruiting | Sponsor: Fog Pharmaceuticals, Inc.

Metastases • New P1/2 trial • Colorectal Cancer • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • APC • CTNNB1 • MSI • MYC

FogPharma Announces First Patient Dosed in Phase 1/2 Clinical Trial of First-in-class TCF-blocking β-catenin Inhibitor, FOG-001, in Advanced Solid Tumors (Businesswire) - "FogPharma...announced the first patient has been dosed in a first-in-human Phase 1/2 clinical trial of, FOG-001, the company’s first-in-class TCF-blocking β-catenin inhibitor. FOG-001 represents the first development candidate arising from FogPharma’s pioneering Helicon™ therapeutics, a new class of drugs capable of modulating protein-protein interactions that may otherwise be challenging to drug....The first-in-human, multicenter, open-label, non-randomized dose escalation and dose expansion Phase 1/2 trial will aim to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics, and antitumor activity of FOG-001 in up to 200 patients with Wnt/β-catenin signaling pathway activated advanced or metastatic solid tumors, with an initial focus on colorectal cancer (CRC)."

Trial status • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

FogPharma Announces $178 Million Series D Financing to Advance Pipeline of First-in-Class Helicon Polypeptide Therapeutics Targeting Major Cancer Drivers (Businesswire) - "Proceeds from the Series D financing will be used to advance and accelerate FogPharma’s growing pipeline of hyperstabilized α-helical (Helicon™) polypeptide therapeutics, a proprietary new class of drugs designed to overcome the limitations of today’s precision medicines with broad applicability to the vast majority of disease targets and therapeutic areas. FogPharma’s lead Helicon polypeptide development candidate, FOG-001, a first-and-only-in-class direct TCF-blocking β-catenin inhibitor with potential applicability to significant cancer patient populations, is expected to enter clinical development in mid-2023. In addition, FogPharma is advancing other first-in-class programs against important, biologically validated cancer targets that have remained elusive to other approaches including TEAD, NRAS, Pan-KRAS, ERG and Cyclin E1."

Financing • New trial • Oncology