arGentis is developing ARG201, a treatment for diffuse cutaneos systemic scleroderma (dcSSc), an autoimmune disease leading to widespread collagen build up on the skin and within the vascular structures of internal organs, resulting in co-morbidities such as pulmonary hypertension, kidney and gastrointestinal track failure, pulmonary fibrosis and death. dcSSc is an orphan disease with approximately 100,000 patients each in the U.S. and and 150,000 in the EU.
 
​The mechanism of action of ARG201 is to induce immune tolerance, whereby the body ceases attacking type I collagen, a primary autoantigen in SSc. There are currently no approved therapies for the underlying cause of SSc. Median survival from diagnosis is approximately 11 years. ARG201 has been granted orphan drug status in the US by the Federal Drug Administration (FDA) and in the EU by the European Medicines Agency (EMEA).  

ARG201 is a bovine-derived Type I collagen which induces immune tolerance in patients with Diffuse Systemic Scleroderma (dcSSc).  It has been designated a biologic by the FDA and there is no evidence of toxicity in human clinical trials.  The Gut-Associated Lymphiod Tissue (GALT) contains 1/3 of the body’s immune cells and is effective in mounting a tolerogenic response to ingested ARG201. Oral administration of the ARG201 suppresses the immune responses via the GALT.  

ARG201 has completed a 168-patient Phase II US clinical trial which confirmed the following key points:

• Induced immune tolerance to CI and was effective in improving skin scores and other outcome variables in patients with dcSSc.
  
• At 15 months the MRSS was significantly lower by 7.3 points (p=0.006) confirming the application to late stage patients (those with the disease 3 years or more) and that a 15 to 18-month time on treatment clinical trial will be appropriate.
• Oral bovine CI at doses of 500 μg/day induced oral tolerance to CI in the study patients confirming the appropriate dose of ARG201 and that it is effective in late-stage patients.
• Subsequent to the trial a genotype marker, designated ROT1, was discovered which identifies which patients will respond to ARG201.  This enables ARG201 to treat only patients who will respond to treatment.
  

The Modified Rodnan Skin Score (MRSS) is the widely recognized tool to measure the extent of skin thickening and is useful for assessing the overall disease activity.  ​The MRSS improvement in the late-stage patients at 15 months was  7.3 points at p=0.006.  

​

​
​

The improvement utilizing the ROT1 screen was 7.2 points at 12 months at p=0.0296 and 8.4 points at 15 months at p=0.007.  The targeted improvement was 5.0 points and these results indicate that the desired improvement may be attained as early as 12 months with the ROT1 screen.  

In the late-stage patients, the improvement above the target at 15 months was 7.3 vs. 5.0, exceeding the target by ~50%.  After screening for ROT1, the improvement vs. target at 15 months was 8.4 vs. 5.0 exceeding the target by 68%.