Scientific Platform
Laurel Biotherapeutics is engineering a kidney-penetrating VHH nanobody agonist of NPR1 — a validated cardiorenal target that larger pharma competitors have failed to close due to format limitations.
Natriuretic Peptide Receptor 1 (NPR1) is a guanylate cyclase receptor activated by atrial and brain natriuretic peptides (ANP/BNP). Agonism of NPR1 drives cGMP-mediated pathways that reduce cardiac preload and afterload while simultaneously promoting natriuresis and diuresis in the kidney.
In patients with acute decompensated heart failure and renal impairment, both organs must be treated simultaneously. Cardio-only approaches worsen renal outcomes. Laurel's VHH format is purpose-built to reach both compartments — enabling true cardiorenal pharmacology.
~15 kDa
VHH Nanobody
Laurel's format
vs
~150 kDa
Monoclonal Antibody
Competitor format
10×
Smaller
Dramatically reduced molecular weight enables tissue penetration impossible with full-size mAbs
Superior
Kidney Uptake
Glomerular filtration and proximal tubule reabsorption drive high renal tissue concentrations
Better
Biodistribution
Favorable PK profile with tissue distribution to both cardiac and renal compartments
NPR1 agonism is clinically validated — Regeneron and Lilly have active programs. Novartis advanced and terminated due to insufficient efficacy, attributable to the mAb format's inability to penetrate kidney tissue. Laurel's VHH format directly addresses this gap.
| Company | Program | Format | Status | Renal Penetration |
|---|---|---|---|---|
| Regeneron | REGN5381 | Monoclonal antibody | Ongoing Ph2 | Limited kidney penetration |
| Novartis | Undisclosed | Monoclonal antibody | Terminated | Insufficient tissue distribution |
| Lilly | Undisclosed | Monoclonal antibody | Ongoing Ph1 | Standard biodistribution |
| Laurel Biotherapeutics | Lead VHH | VHH Nanobody (~15 kDa) | Preclinical | Superior kidney penetration |
Generative AI has produced approximately 60 VHH candidate sequences computationally designed to bind NPR1. These candidates carry high-confidence pLDDT structural scores from AlphaFold-based validation, indicating well-folded, stable antibody domains ready for wet-lab evaluation.
By entering the binding evaluation stage with a pre-validated computational library, Laurel bypasses the earliest and most time-consuming step in traditional antibody discovery. This accelerates the path from candidate identification to in vivo proof-of-concept by an estimated 6–12 months versus conventional approaches.
01
~60 AI-generated candidate sequences with high-confidence pLDDT structural scores ready for binding evaluation against NPR1.
02
Llama immunization with NPR1 antigen to generate a diverse in vivo immune repertoire enriched for target binders.
03
High-throughput phage display library screening to identify VHH candidates with optimal affinity and selectivity profiles.
These three modalities are run in parallel — not sequentially — maximizing the diversity of binding candidates while compressing the overall discovery timeline. The combined library will be screened against NPR1 to identify the highest-affinity VHH leads for optimization.