The field of inflammatory bowel disease (IBD) treatment is witnessing a breakthrough as Sorriso Pharmaceuticals advances the development of an oral VHH antibody therapy for ulcerative colitis (UC). The private biotech startup recently presented  Phase 1b clinical trial data at a medical conference, offering early indications of clinical efficacy and paving the way for a larger Phase II study.

A Game-Changer for IBD Treatment

Current treatments for ulcerative colitis and Crohn’s disease primarily rely on intravenous (IV) infusions or injections of monoclonal antibodies, which can lead to systemic side effects. However, oral administration of biologics has long been challenging due to the large molecular size (150 kDa) of traditional monoclonal antibodies, making it difficult for them to remain stable and effective in the digestive tract.

Sorriso’s drug, SOR102, is an oral dual VHH antibody therapy targeting TNF-alpha and IL-23, two key inflammatory cytokines implicated in IBD pathogenesis. Unlike conventional monoclonal antibodies, SOR102 leverages single-domain VHH antibodies, which are significantly smaller and more stable. The therapy incorporates a specialized amino acid linker designed to cleave upon exposure to trypsin, an enzyme abundant in the digestive tract, ensuring targeted activation within inflamed tissues.

Encouraging Phase 1b Clinical Trial Results

Sorriso’s Phase 1b trial involved 22 patients with ulcerative colitis, testing the safety and efficacy of SOR102 over a six-week period. Participants were divided into three groups:

- Placebo group (6 patients)

- Once-daily 810 mg SOR102 group (7 patients)

- Twice-daily 810 mg SOR102 group (9 patients)

While the trial primarily focused on safety, efficacy markers such as endoscopic response — a key measurement for clinical remission—were also evaluated. The results indicated:

- Two out of nine (22%) patients in the twice-daily dosing group achieved an endoscopic response.

- In the “per protocol” population, excluding patients who dropped out for non-treatment-related reasons, two of five patients (40%) responded positively.

- The overall response rate is comparable to monotherapy biologics, while the per protocol response rate surpasses traditional monotherapies.

The study was conducted in Ukraine and Georgia, and some patients dropped out for reasons unrelated to treatment, including disease severity and relocation.

Why This Matters: The Potential of Oral VHH Antibodies

Sorriso’s Vorabodies represent a novel class of single-domain antibodies engineered for oral delivery. These VHH-based therapeutics are designed to directly access and maintain activity within inflamed intestinal tissue, differentiating them from conventional biologics. If successful, SOR102 could revolutionize the treatment landscape for IBD, providing patients with a convenient, effective, and well-tolerated alternative to existing IV and injectable therapies.

The Future of Oral Biologics in IBD

With Phase 2 trials on the horizon, Sorriso Pharmaceuticals is moving closer to bringing the first oral VHH-based therapy to market for ulcerative colitis. This development underscores the growing potential of nanobody technology in gastrointestinal diseases, reinforcing the advantages of stability, specificity, and targeted delivery that VHH antibodies offer.

At AlpalifeBio, we are committed to advancing VHH antibody-based therapeutics through our Naïve Camelid VHH Antibody Phage Display Library. If you are interested in leveraging single-domain antibodies for drug discovery, we welcome collaboration opportunities.

Stay updated with the latest breakthroughs in nanobody technology!

Reference: Endpoint News by Max Gelman on February 27th, 2025

https://sorrisopharma.com/science/