Therapeutics targeting cell adhesion.
Zonula uses AI-driven discovery to find small molecules for rheumatoid arthritis — a fundamentally new approach that targets the joint-destroying fibroblasts, not the immune system.
A new approach to treating arthritis.
Zonula uses AI-driven discovery to find small molecules for the treatment of rheumatoid arthritis (RA). These small molecules target the fibroblasts in bone joints, rather than the cells of the immune system. This represents an entirely new approach to treating arthritis. The small molecules control the function of cell-surface glycoproteins called cadherins. They are inexpensive to manufacture and act in a different manner than existing RA drugs. Zonula holds U.S. patents on several of these molecules.
Zonula has assembled a world-class team to perform discovery and development of RA targets and small molecules. The team has over a century of combined biotechnology experience across biology, chemistry, AI and drug development.
Inhibiting fibroblast adhesion to stop joint erosion.
Zonula's small molecules inhibiting fibroblast adhesion represent a new approach to treating rheumatoid arthritis (RA).
Cell adhesion — the process by which cells stick to one another — is a fundamental biological property. Zonula's small molecules bind to cell-surface glycoproteins known as cadherins (biological glues) and prevent cell adhesion. These molecules control fibroblast adhesion, activity and survival in bone joints.
Inflammation occurring during RA causes fibroblasts in bone joints to proliferate and erode the cartilage. Zonula's small-molecule cadherin inhibitors stop the fibroblasts from proliferating and decrease their ability to degrade cartilage.
Millions of patients still have no adequate option.
Rheumatoid arthritis is a chronic, systemic, inflammatory autoimmune disease that damages joints, leading to disability and increased mortality.
The unmet need
Approximately 20% of people with RA do not get adequate relief from available medications. 40% of patients fail to respond to first-line treatments like methotrexate and require biologic or targeted synthetic drugs.
The three main targeted RA drugs are the TNF-α inhibitors Humira and Enbrel, and the JAK inhibitor Rinvoq. 30–40% of patients with RA are not responsive to TNF-α-based therapies — non-anti-TNF-α therapies are needed.
- Liver toxicity — methotrexate
- Increased risk of serious infections — TNF-α and JAK inhibitors
- Increased risk of major adverse cardiovascular events — JAK inhibitors
Target the cells responsible for cartilage destruction
Fibroblast-like synoviocytes (FLS) proliferate in the bone joints during the development of rheumatoid arthritis and subsequently degrade the cartilage. Zonula has identified novel small molecules that prevent FLS proliferation and bone degradation. These small molecules inhibit the activity of new RA targets — cadherins — on the surface of FLS. Zonula intends to develop these small molecules as RA therapeutics.
Over a century of combined drug-discovery experience.
Zonula works with an extensive worldwide network of highly skilled professionals with years of experience in biology, chemistry, AI and drug development.
Orest Blaschuk
Orest has worked in cell biology and translational research for over three decades. He was a tenured Associate Professor in the Faculty of Medicine at McGill University from 1987–2021 (retired). Before starting Zonula, he co-founded Adherex Incorporated in 1996, a publicly traded McGill spin-off oncology company, where he served as Chief Scientist (1996–2005) and consultant (2005–2009). Adherex developed anti-cancer drugs targeting cell-adhesion molecules based on intellectual property from Orest's laboratory at McGill. The Adherex drug ADH-1 — a cyclic peptide targeting N-cadherin — reached Phase II clinical trials as an anti-cancer agent and received FDA orphan-drug status for melanoma. Orest has authored 88 scientific articles (6,000+ citations) and is an inventor on 51 U.S. patents.
Xavier Barbeau
Xavier is an AI and computational drug-discovery chemist with a decade of experience. He blends medicinal chemistry, biochemistry and structural-biology data with computational chemistry and AI tools to support translational decision-making. He has held computational chemistry roles at Feldan Therapeutics, NuChem Sciences, and most recently at Sygnature Discovery, where he led a major AI-for-drug-discovery project. Xavier is the author of over 30 publications and an inventor on 6 patents, spanning small-molecule drug discovery, peptide-based intracellular delivery, and open-source tool development.
Dalfonie Banerjee
Dal is COO of Zonula. She is a strategic, solution-focused entrepreneur with 30 years of global pharmaceutical, biotechnology, and life sciences experience. Expertise includes communications, marketing, change management, and project management. Known for successfully delivering complex projects in knowledge-driven, high-energy settings and catalyzing accelerated success. Invited speaker and the recipient of over 30 awards. Currently she holds the position of CEO at 3Sixty Pharma Solutions LLC.
Research & milestones.
Zonula notes two publications describing the ability of N-cadherin to regulate fibrosis
and arthritis. They describe N-cadherin forming complexes with (1) FGF receptors to stimulate
fibrosis (e.g. idiopathic pulmonary fibrosis) and (2) metalloproteinases (ADAM15) to promote
arthritis. They suggest N-cadherin antagonists — inhibitors of cell–cell adhesion — have
potential as anti-fibrotic and anti-arthritic drugs.
doi.org/10.1080/21688370.2025.2532160 ·
doi.org/10.1038/s41598-025-94012-2
Zonula notes the publication of a detailed review on the involvement of N-cadherin in
leukemia. Written by Jessica Parker, Sean Hockney and Deepali Pal of Northumbria University
and Orest Blaschuk of Zonula, it discusses acute pediatric leukemia and opportunities to
target N-cadherin-mediated leukemia-cell adhesion in the bone marrow — where it protects
cancer cells from chemotherapy. Zonula's small-molecule N-cadherin inhibitors could disrupt
this adhesion and sensitize cancer cells to chemotherapeutics.
doi.org/10.1017/erm.2023.13
Zonula notes a study validating N-cadherin as a therapeutic target for leukemias.
Drug-resistant leukemia cells adhere to support cells in the bone marrow via N-cadherin.
Investigators at Newcastle University showed that the N-cadherin inhibitor ADH-1 disrupts
this adhesion, activating the cells and sensitizing them to chemotherapeutics
(Cell Reports Medicine 3:100717) — proof-of-concept that N-cadherin inhibitors can treat
blood cancers. ADH-1 is a first-generation N-cadherin therapeutic discovered by Dr. Orest
Blaschuk, founder of Zonula. Zonula is developing superior second-generation small-molecule
N-cadherin inhibitors.
sciencedirect.com/…/S2666379122002609
Zonula notes the publication of a review article discussing the raison d'être of the
company (Front. Cell Dev. Biol., March 3, 2022).
doi.org/10.3389/fcell.2022.866200
Zonula notes a study further validating N-cadherin in brain cancer. N-cadherin has emerged
as a potential target for three brain cancers — meningioma, neuroblastoma and glioblastoma
multiforme — which currently lack adequate treatments. Zonula's N-cadherin inhibitor was shown
to kill glioblastoma multiforme cells (Biochem. Biophys. Res. Commun. 529:162-168). ADH-1 was
shown to kill neuroblastoma cells (PLoS ONE 7(2):e31206), and to block meningioma tumorigenesis
in an organoid model (Nature Communications 11:4803). These studies underscore N-cadherin as a
therapeutic target in brain cancers.
doi.org/10.1016/j.bbrc.2020.06.001 ·
doi.org/10.1371/journal.pone.0031206 ·
nature.com/articles/s41467-020-18582-7
Zonula announces a study demonstrating that its lead small-molecule N-cadherin inhibitor
kills glioblastoma multiforme cells (Biochem. Biophys. Res. Commun. 529:162-168). Conducted by
Dr. Orest Blaschuk with Dr. Stephanie Willerth (University of Victoria), the study used a
bioprinted tumor model of glioblastoma cells, astrocytes and biomaterial. Targeting N-cadherin
represents a new approach to treating this lethal brain cancer.
doi.org/10.1016/j.bbrc.2020.06.001
The USPTO allows a continuation of U.S. Patent 10,494,345 — describing the use of a small molecule that modulates cell adhesion to treat fibrosis-dependent diseases (U.S. Patent 10,647,672). The molecule inhibits fibroblast adhesion by blocking N-cadherin, and can be used for cancer, idiopathic pulmonary fibrosis, restenosis, sclerosis, and rheumatoid arthritis.
The USPTO allows Zonula's application describing small molecules capable of modulating cell adhesion (U.S. Patent 10,494,345). Methods of using these molecules to enhance or inhibit cadherin-mediated functions are disclosed — for diseases including idiopathic pulmonary fibrosis and cancer — along with compositions, devices, and synthesis methods.
Let's talk investment & partnering.
Zonula is currently seeking Seed funding to support studies leading to an Investigational New Drug (IND) filing. For more information or to discuss investment and partnering opportunities, please get in touch.