4D pharma has started dosing in a phase 1 clinical trial with Thetanix for the treatment of Paediatric Crohn's disease ('PCD').
PCD is a rare chronic inflammatory bowel disease that is caused by the malfunction of the immune system leading to inflammation, or swelling, across the lining of the digestive tract.
Crohn's disease most often affects the end of the small intestine, but can occur anywhere along the digestive tract from mouth to anus. In addition to gastrointestinal symptoms (diarrhoea, rectal bleeding, abdominal pain), children with PCD often experience growth failure, malnutrition, pubertal delay and bone demineralisation.
Approximately 20% of patients with Crohn's disease present when they are younger than 20 years, and it is estimated that there are around 41,000 children in the United States with PCD.
Current treatment regimens focus on the induction of remission through the use of corticosteroids and biologics, with immunosuppressants and biologics used as maintenance therapies. Whilst these treatments are capable of resolving symptoms, they do not address the underlying cause of the disease.
Furthermore, long-term use may reduce the response rate over time and is also associated with serious side effects, such as the development of cancers and deleterious effects on children's growth and bone health. Up to 29% of children require surgery within 3 years of diagnosis of PCD.
Thetanix is a live biotherapeutic, a new class of regulated therapeutics using bacteria to treat or cure disease.
Thetanix is a bacteria that was isolated from the gut of a healthy human subject. The development of Thetanix as a therapeutic is based on over two decades of research into the interaction of this bacteria and the human gut. This work has demonstrated that Thetanix has a specific role in modulating the immune system and has anti-inflammatory properties.
Thetanix received orphan drug designation from the FDA in October 2013.
The phase 1 trial of Thetanix has now commenced and the Company is pleased to report that the first subject in the trial has been dosed. This study is a single (Part A) and multiple (Part B) dose study. Following informed consent and screening, 10 eligible subjects with PCD will receive a single dose of Thetanix or placebo in the clinic.
A Safety Review Committee will review the safety data up to Day 7 from these first 10 subjects and determine if it is appropriate to continue into Part B in which 10 subjects will receive 15 doses of Thetanix or placebo in a twice daily dosing regimen over 7.5 days. In both parts of the study, 8 of the 10 subjects will randomly receive Thetanix and 2 subjects will randomly receive placebo.
The Primary Outcome Measure of the study will focus on the safety and tolerability of the Thetanix product, whilst the Secondary Outcome Measures include assessment of Weighted Paediatric Crohn's Disease Activity Index and analysis of the microbiome of subjects and an inflammatory marker of disease.
The live biotherapeutics being developed by 4D are initially isolated from healthy human subjects. Once isolated and verified as therapeutically relevant, live biotherapeutics are produced, as with all other drugs, in accordance with strict pharmaceutical regulations. Importantly, Thetanix and 4D's other live biotherapeutics are believed to bring a new dimension to safety.
As the initial source material is from healthy human subjects, live biotherapeutics are expected to have significantly reduced (or no) side effects associated with currently approved drugs including both small molecules and biologics. This offers the potential to develop a new class of efficacious drugs with vastly improved safety and tolerability.
Dr. Alex Stevenson, 4D's Chief Scientific Officer, commented: "Coming shortly after the completion and analysis of the Blautix phase 1 results, the dosing of the first subject in the Thetanix phase 1 clinical trial for Paediatric Crohn's Disease is an important milestone for 4D. With our proprietary MicroRx platform we continue to develop new therapeutic areas of interest and build on our existing patents, as well as develop new intellectual property.
"In addition, by bringing on stream our in-house production facilities, we are able to deliver consistent pharmaceutical grade product. These facilities allow 4D to control the progress of the MicroRx pipeline toward the clinic, including additional clinical trials planned in a number of other therapeutic areas including asthma, cancer and Paediatric Ulcerative Colitis. We continue to consolidate our position in this new and emerging field and look forward to reporting on our continuing progress over the coming months."