Tiziana Life Sciences PLC (NASDAQ:TLSA) has announced the initiation of a Phase 1b clinical trial to evaluate orally administered enteric-coated capsules of foralumab in patients with mild-to-moderate Crohn's Disease (CD).
The revised protocol, as previously outlined in the company's announcement on February 4, 2022, allows for the study of a broader patient population and a shorter dosing period. These protocol amendments or revisions are intended to expedite patient enrollment with study completion targeted for the fourth quarter of 2022.
This study is the first multiple-dose study with orally administered enteric-coated capsules of foralumab in patients with CD. The study will initiate soon with patient enrollment in the second quarter of 2022. Enteric-coated capsules, containing doses up to 5 mg of foralumab, will be administered once-daily for five consecutive days to patients with mild-to-moderately active CD.
Dr Kunwar Shailubhai, chief executive officer and chief scientific officer of Tiziana, commented: "The oral route of administration is the preferred route for all pharmaceuticals. The 'Holy Grail' for biologics is the 'switch' from parenteral (IV, SC) to oral administration as it is the most economical, non-invasive, and convenient route with respect to patient's quality of life and compliance."
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"We have developed proprietary formulation technologies, enabling oral, nasal, and inhalation routes for administration of antibodies, to facilitate local action at the respective target sites. We believe this Phase 1b study is a logical first step towards the clinical validation of oral immunotherapy with foralumab capsules, to provide local action rather than systemic delivery, for CD treatment," Dr Shailubhai added.
While the primary objective is safety and tolerability, additional endpoints are to assess clinical and immune signal responses, including calprotectin measurements in stool. Blood samples will be collected to evaluate pharmacokinetics, including the rate and extent of systemic absorption. The presence of anti-drug antibodies (ADAs) will also be determined.
Typically, therapeutic antibodies are administered either intravenously or subcutaneously, but severe and sometimes life-threatening side effects may occur. Oral administration with foralumab is a novel approach to induce an anti-inflammatory immune response via site-targeted immunomodulation in the gut.
Previous mouse and patient studies have demonstrated that orally delivered anti-CD3 antibody effectively ameliorates gut inflammation in a murine model of colitis1 and in patients with moderate-to-severe ulcerative colitis2. Currently, commonly used immunotherapies for CD require intravenous or subcutaneous administration of anti-TNF-alpha antibodies, such as HUMIRA, REMICADE, and anti-CD23 antibodies (STELARA).
Dr Howard Weiner, director of the Multiple Sclerosis Program at the Brigham and Women's Hospital (BWH) and Chairman of Tiziana's Scientific Advisory Board, commented: "Treatment with orally or nasally administered foralumab is a novel physiological approach to stimulate the mucosal immune system to induce disease-modifying benefits while minimizing the toxicities that are commonly associated with the traditional intravenous or subcutaneous immunotherapies.
"In this regard, the first validation of our innovative approach came from our recently reported clinical results showing positive clinical benefits in a patient with secondary progressive multiple sclerosis (SPMS), who was treated for 6 months with intranasally administered foralumab3."
Tiziana Life Sciences is a clinical-stage biopharmaceutical company developing breakthrough therapies using transformational drug delivery technologies to enable alternative routes of immunotherapy.
The company's innovative nasal, oral, and inhalation approaches in development have the potential to provide an improvement in efficacy as well as safety and tolerability compared to intravenous (IV) delivery. Tiziana's two lead candidates, intranasal foralumab, the only fully human anti-CD3 mAb, and milciclib, a pan-CDK inhibitor, have both demonstrated a favorable safety profile and clinical response in patients in studies to date.
Tiziana's technology for alternative routes of immunotherapy has been patented with several applications pending and is expected to allow for broad pipeline applications.
Contact the author at jon.hopkins@proactiveinvestors.com