On June 5, 2023 FogPharma, a biopharmaceutical company committed to transforming the lives of patients through a new precision medicine approach widely applicable to important and challenging intracellular targets, reported 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 (Press release, FogPharma, JUN 5, 2023, View Source [SID1234632497]). 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.

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"The Wnt/β-catenin signaling pathway is one of the most frequently activated oncogenic pathways and a well-described driver of many cancers, but this target had been frustratingly beyond therapeutic reach until the discovery of FOG-001," said Gregory Verdine, Ph.D., founder and chief executive officer of FogPharma. "I am proud of our team’s inventiveness, hard work and dedication towards advancing our exceptional science to this very important milestone and look forward to FogPharma’s next chapter as a clinical-stage company."

"FOG-001 has the potential to become a significant new treatment option for the large number of cancer patients whose disease is driven by derangement of the Wnt/β-catenin pathway, including those with colorectal cancer," said Mathai Mammen, M.D., Ph.D., who will become chairman, president and chief executive officer of FogPharma on June 12, 2023. "Metastatic colorectal cancer is a devastating malignancy with increasing prevalence and few approved therapies directly targeting oncogenic driver mutations. These patients are in need of novel therapeutic options. We look forward to characterizing the safety, tolerability and anti-tumor activity of FOG-001 in this Phase 1/2 trial."

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). The Phase 1 portion aims to enroll 60 patients and will assess the safety and tolerability of FOG-001 across a range of dose levels to determine the best doses to progress to the Phase 2 portion. The Phase 2 portion will aim to enroll up to 140 patients to further characterize the safety, tolerability and anti-tumor activity of single-agent FOG-001 at the recommended Phase 2 dose.

About Fog-001

FOG-001 is a first-in-class TCF-blocking β-catenin inhibitor. FOG-001 represents the first of FogPharma’s proprietary, conformationally stabilized α-helical polypeptide (Helicon) therapeutics, a new class of drugs that combine the cell-penetration of small molecules with the broad target engagement of protein therapeutics. Helicons are uniquely capable of modulating disease-relevant interactions that have otherwise proven challenging to drug.

FOG-001 combines key features that distinguish it from previously reported Wnt/β-catenin pathway modulators: FOG-001 acts inside the cell where it binds directly to the key oncogenic driver β-catenin; and FOG-001 blocks the Wnt pathway at the most downstream node, disrupting the interaction between β-catenin and the transcription factor TCF, thereby abrogating the signal transmission by which Wnt pathway mutations are believed to drive oncogenesis.

In biochemical and cellular studies, FOG-001 has been shown to potently and selectively disrupt the interaction of β-catenin with TCF. Preclinical studies have demonstrated the ability of FOG-001 to cause tumor growth inhibition and complete regression by disrupting β-catenin-dependent signaling. FOG-001 is currently being evaluated in a first-in-human Phase 1/2 clinical trial in patients in participants with Wnt/β-catenin signaling pathway activated advanced or metastatic solid tumors.