Parabilis Medicines Presents Updates on Clinical Progress of β-cateninTCF4 Inhibitor, Helicon™ Portfolio and Discovery Engine at J.P. Morgan Healthcare Conference

Early clinical data for FOG-001, first and only direct inhibitor of β-catenin_TCF4, demonstrate monotherapy antitumor activity and in-tumor target engagement

FOG-001 monotherapy and combination study cohorts underway; Phase 1 colorectal cancer data to be shared later this year

First-in-class ERG targeted protein degrader demonstrates in vivo proof-of-concept in prostate cancer model

Parabilis Medicines (formerly Fog Pharmaceuticals), a clinical-stage biopharmaceutical company dedicated to creating extraordinary medicines for people living with cancer, today presented updates from its targeted first-in-class oncology programs at the 43^rd Annual J.P. Morgan Healthcare Conference in San Francisco.

The presentation by Mathai Mammen, M.D., Ph.D., Chairman and CEO of Parabilis Medicines, highlighted recent advances in the Company’s versatile and tunable Helicon™ platform. This powerful peptide platform is capable of entering cells and potently and selectively binding proteins where small molecules cannot, drugging otherwise undruggable targets. Recent technical breakthroughs have led to an expanded range of powerful applications for Helicons across three main areas: functional inhibitors of intracellular protein-protein interactions, targeted protein degraders, and targeted radiopharmaceuticals. Additionally, the Company provided an update from its lead program, FOG-001, which is being evaluated in an ongoing Phase 1/2 study for microsatellite stable (MSS) colorectal cancer and other Wnt-pathway activated (WPAM+) solid tumors.

“We’ve made significant leaps forward in the last year in both experimental and data science technologies, propelling us toward an even deeper understanding and practical applications of the unique capabilities of Helicon peptide therapeutics,” said Dr. Mammen. “Promising data from our ongoing Phase 1/2 trial show that FOG-001 is a bona fide β-catenin _TCF4 inhibitor, confirming Helicons’ ability to target proteins previously considered undruggable in patients. FOG-001 could represent an expansive opportunity with the potential to provide benefit across multiple common cancer types, including colorectal cancer. We expect 2025 to be an eventful year, including the planned presentation of FOG-001 clinical results and the advancement of additional first-in-class pipeline programs including our ERG degrader for prostate cancer toward the clinic.”

Program Updates and Expected 2025 Milestones

FOG-001

FOG-001 is the first and only direct inhibitor of β-catenin_TCF4, which drives the vast majority of colorectal cancers and plays a significant role in several other cancer types. FOG-001 is currently being evaluated in a Phase 1/2 clinical trial (NCT05919264), and more than 60 patients with locally advanced or metastatic solid tumors have been dosed to date.

Early clinical data for FOG-001 confirm monotherapy antitumor activity with a manageable safety profile. Furthermore, paired biopsy transcriptomic and immunohistochemistry analyses have confirmed FOG-001’s in-tumor target engagement, eliciting important biological changes within the tumor microenvironment, including increased markers of inflammation, decreased markers of stemness, and increased markers of cellular differentiation. These clinical observations, coupled with preclinical data, provide a strong biological rationale for continued development of FOG-001 as a monotherapy and for evaluating multiple combination cohorts. Preliminary Phase 1/2 data are expected to be shared publicly in 2025.

ERG Degrader

The presentation also featured first-in-industry data demonstrating in vivo degradation of ERG, a longstanding high-value target in prostate cancer. ERG fusions have been implicated in 40-50% of all prostate cancer cases, and a Helicon-based targeted ERG degrader could provide a novel therapeutic option for patients with metastatic castrate-resistant prostate cancer (mCRPC). In vivo proof-of-concept data in preclinical models of prostate cancer showed robust activity with coincident ERG degradation confirmed by immunohistochemistry. The Company’s ERG degrader program is expected to advance into IND-enabling activities in 2025.

Radioligand Therapies

In May 2024, Parabilis Medicines and ARTBIO announced a collaboration to co-develop Helicon-enabled alpha radioligand therapies (HEARTs) incorporating the potential best-in-class isotope Lead-212 (also called ²¹²Pb). The Company has identified multiple Helicons with sub-nanomolar affinity for the lead target. The collaboration continues to rapidly advance programs against multiple novel radioisotope targets.

About Parabilis Medicines (Formerly FogPharma)

Parabilis Medicines™ is a clinical-stage biopharmaceutical company dedicated to creating extraordinary medicines for people living with cancer. Through its pioneering Helicon™ discovery platform, Parabilis is engineering precisely tuned, stabilized helical peptide therapeutics that have the potential to unlock a large number of traditionally undruggable targets. FOG-001, the company’s first-in-class TCF-blocking β-catenin inhibitor (β-catenin _TCF4) and lead clinical program, is being evaluated in a Phase 1/2 study for patients with colorectal cancer and other solid tumors and is proof of the applicability of the platform to address undruggable intracellular protein-protein targets. The company is additionally advancing a pipeline of other first-in-class programs that target proteins known to be relevant to numerous cancers, but considered intractable with traditional drug modalities. The versatility of the Helicon approach allows for the discovery of multiple targeting mechanisms, including functional protein-protein interaction inhibitors, bifunctional degraders, and radiopharmaceuticals. Parabilis is headquartered in Cambridge, Mass., and is well-capitalized, with more than $500 million raised to date from leading life sciences investors. For more information, please visit: www.parabilismed.com

About FOG-001

FOG-001 is an investigational first-in-class competitive inhibitor — and the only direct inhibitor — of β-catenin interactions with the T-cell factor (TCF) family of transcription factors, and is currently in clinical development. By directly targeting the β-catenin_TCF4 protein-protein interaction, the most downstream node in the Wnt pathway, FOG-001 is intended to block the Wnt signaling pathway irrespective of the particular mutations driving disease.

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. FOG-001 is currently being evaluated in a first-in-human Phase 1/2 clinical trial in patients with locally advanced or metastatic solid tumors.

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