Biomarker-driven approaches guide research and clinical development

Our pipeline is currently comprised of monoclonal antibodies (mAb) that target cell surface receptors. Upon binding, they can reduce the activation of pathogenic responses in autoimmune and inflammatory conditions.

Potential best-in-class mAb product candidates

Program
(Target)
Lead
Indication
Discovery
IND-enabling
Phase 1/2
PIVOTAL
Partner
Membranous
nephropathy
Cancer Research logo
Thyroid
eye disease
Pierre Fabre logo
Chronic
urticaria
Novelty logo
Eosinophilic
asthma
Valenzabio logo
VB119

VB119: An anti-CD19 mAb in clinical trials for rare renal autoimmune indications including membranous nephropathy (MN) and minimal change disease (MCD)

VB119 is an IgG1 mAb with enhanced antibody-dependent cellular cytotoxicity (ADCC) and potent binding to CD19, a B-cell surface receptor found on autoantibody-secreting cells (ASCs). ASCs are closely linked to several autoimmune diseases, including membranous nephropathy (MN). Pathogenic ASCs often lack expression of CD20 and are not targeted by anti-CD20 antibodies such as rituximab.

Proof-of-mechanism for VB119 was established in a completed Phase 1 clinical trial, where peripheral B-cell depletion was observed in most patients after a single dose of VB119. VB119’s ability to bind and eliminate disease-causing ASCs that are not directly targeted by conventional therapies has the potential to provide clinical benefit for patients with MN, as well as other autoantibody-mediated diseases.

We are initiating an open-label, Phase 1b/2a clinical trial of VB119 in primary MN patients with nephrotic-range proteinuria. This trial is a multi-center, open-label study to evaluate the safety, pharmacokinetics, and efficacy of VB119. Key assessments include serum anti-PLA2R antibodies and proteinuria.

HIGHLIGHTS

  • Two open INDs in orphan kidney diseases with no approved treatments
  • Ongoing Phase 1b/2a studies in MN with proof-of-concept second half of 2022
  • Both clinical programs supported by proteinuria-based primary endpoints
  • Phase 2a data expected second half of 2023
If you are a patient with MN or a clinical investigator in the US or UK and are interested in learning more about our study, please visit:

Ongoing Phase 1b/2a study at-a-glance

Enrollment
  • ~30 sites across US, UK, & Lat Am
  • UPCR ≥2.0 g/g
  • B-cell count >LLN (80 cells/µL)
Dose cohorts*
  • 2 doses 14 days apart*
    • 100 mg
    • 200 mg
    • 400 mg
Design
  • N ≈ 30, single-arm, open-label
  • Dose escalation & expansion
  • 18-month follow-up
Endpoints
  • Safety, tolerability & PK
  • B-cell depletion
  • Proteinuria response
  • Anti-PLA2R antibody response

*Initial treatment period; maintenance regimen allowed at 6 months based on subjects achieving pre-specified clinical or immunological response criteria.

About membranous nephropathy (MN)

In MN, anti-PLA2R antibodies are thought to attack the GBM, leading to a leaky membrane and the onset of nephrotic syndrome

Anti-PLA2R antibodies

Pathogenesis of MN is autoantibody-mediated with CD19-positive B-cells intensely secreting IgG autoantibodies that target the kidney

Membranous nephropathy (MN) is an autoimmune disease caused by autoantibody-induced damage to cells that line the surface of glomerular capillaries in the kidney. This inflammatory process causes thickening and breakdown of the glomerular basement membrane (GBM), which can result in heavy and persistent proteinuria. The severity of proteinuria varies depending on the extent of kidney injury and often leads to nephrotic syndrome, which can be disabling for patients. Patients with nephrotic syndrome are at risk of progressing to kidney failure.

Learn more about MN more
Learn more about our clinical trial more
VB421

VB421: An anti-IGF-1R mAb with a lead indication for thyroid eye disease (TED)

VB421—the most potent anti-IGF-1R mAb in development—has the potential to be a best-in-class TED therapeutic. In addition to TED, VB421 is also being explored for other inflammatory and fibrotic indications where IGF-1R signaling is implicated.

VB421 was discovered by Pierre Fabre Medicament, which has been studying and developing anti-IgF-1R antibodies for over 20 years.

VB421 binds IGF-1R with sub-50 pM potency and no measurable effector function. In addition to high binding affinity, VB421 induces rapid and efficient receptor internalization that could potentially provide a differentiated mechanism of action relative to other anti-IGF-1R antibodies.

HIGHLIGHTS

  • Potential best-in-class treatment for TED
  • Phase 1 Initiated
  • Subcutaneous administration PK/PD data second half of 2022

VB421 at-a-glance

Design

IgG1 humanized

Dose frequency

Q3W 8 doses total

Route of administration

SC*

IGF-1R binding affinity (KD)

<0.03 nM

*Low volume (<2 mL), <10 second injection formulation for subcutaneous delivery. Potential for auto-injector and/or pre-filled syringe, potentially suitable for at-home use.

About thyroid eye disease (TED)

IGF-1R overexpression, activation play a central role in TED pathogenesis

Thyroid eye disease (TED), also known as thyroid-associated ophthalmopathy, Graves’ ophthalmopathy, or Graves’ orbitopathy, is a debilitating and painful autoimmune disease that causes eye bulging and vision change. In serious cases, TED can lead to loss of vision and blindness. The primary pathophysiology of TED is thought to occur via activating autoantibodies to thyrotropin receptors (TSHRs) on orbital fibroblasts.

Stimulation of these receptors leads to downstream IGF-1R-mediated inflammatory processes that cause expanded orbital tissue. This manifests clinically as eye redness, diplopia, and proptosis that can require surgical intervention to prevent or mitigate vision loss. Current treatment options include corticosteroids and the anti-IGF-1R mAb teprotumumab (TEPEZZA®).

Learn more about TED more

TED is thought to occur via activating autoantibodies
to TSHR on orbital fibroblasts

thyroid eye disease (TED)

VB517

VB517: An anti-c-KIT mAb with a lead indication for chronic urticaria (CU)

VB517 is an anti-c-KIT mAb currently in development for the treatment of chronic urticaria (CU). Mast cells (MCs) are derived from bone marrow and develop in response to stem cell factor (SCF), the natural ligand of c-KIT. MC activation can lead to the release of immunomodulatory cytokines, proteases (tryptase), and small molecules (histamine). c-KIT is critical to survival and activation of MCs; blocking c-KIT reduces degranulation and induces apoptosis in MCs. As mast cell activation is implicated in numerous diseases—including anaphylaxis, allergic rhinitis, asthma, atopic dermatitis, food allergies, and others—there are multiple additional indications that could be targeted in the future.

HIGHLIGHTS

  • Potential best-in-class treatment for CU
  • IND filing first half of 2023

VB517 at-a-glance

Design

Fully human IgG1

Route of administration

IV/SC

KD

2.8 pM

Dose frequency

Q2M

About chronic spontaneous and inducible urticaria

Caused by mast cell (MC) degranulation following activation by IgE

Chronic urticaria (CU) is caused by MC degranulation following activation by IgE. It can be spontaneous (idiopathic) or triggered by physical stimuli (e.g., heat). Symptoms include urticaria (hives), itching, erythema, angioedema, headache, fatigue, and pain. About 2 million patients in the US suffer from urticaria at any given time. CU typically begins in the third to fifth decades of life and lasts 2 to 5 years on average; more severe disease tends to have a longer duration. The goal of therapy is to resolve or eliminate urticaria. Current front-line treatment is second-generation H1 antihistamines; second-line agents include H2 antihistamines, leukotriene receptor antagonist, and first-generation H1 antihistamines. Refractory patients are typically treated with omalizumab or other ISTs.

CU is one of multiple diseases thought to occur as a result of mast cell activation

Healthy and activated mast cells