NEW YORK and LONDON—Tiziana Life Sciences plc has announced a collaboration with Parexel Biotech, a division of Parexel International, to conduct a global Phase 1b/2 trial with orally administered, enteric-coated capsules of formulated Foralumab — a fully human anti-CD3 mAb.

Foralumab has shown reduced release of cytokines after intravenous (IV) administration in patients with moderate to severe Crohn’s disease (CD), with decreases in the classic side effects of cytokine release syndrome (CRS). And Tiziana recently reported positive results from a Phase 1 study showing that oral treatment with Foralumab was well tolerated in healthy volunteers, with no drug-related safety issues even at the highest dose of 5 mg.

Now, this Phase 1b/2 clinical study will evaluate the safety, tolerability and clinical activity of escalating doses of capsules of Foralumab. The dose-ranging, open-label study will enroll 60 patients in the U.S. and Europe.

“We understand that this will be the first-ever study with ‘take-home’ capsules of any mAb for immunotherapies for human diseases,” said Dr. Howard L. Weiner, chairman of the scientific advisory board at Tiziana. “We believe the scientific rationale for oral treatment with Foralumab is logical to facilitate topical action at the inflamed sites in the gastrointestinal tract. This potentially ground-breaking approach for immunotherapies originated in my laboratory and was subsequently reported by other researchers in the field.”

“Recently, we also successfully demonstrated that nasally administered Foralumab is not only well-tolerated, but also produced desirable immunological responses,” Weiner continued. “Oral and nasal administration routes are both physiologic approaches to stimulate the mucosal immune system to induce disease modifying benefits.”

Crohn’s disease is a chronic immune system disorder that causes inflammation throughout the digestive tract. Although the specific causes of CD aren’t fully understood, severe gut inflammation caused by an overactive immune system appears to contribute to disease pathology.

“The prevalence of inflammatory bowel disease is rising globally, imposing a significant burden both on patients as well as healthcare systems worldwide. We’re excited to be collaborating with Tiziana to support the development of a novel, oral therapy that could provide Crohn’s patients with another option in their repertoire of treatments to combat this devastating disease,” added Sy Pretorius, M.D., executive vice president, and chief medical and scientific officer of Parexel.

Immunosuppressive agents and anti-TNF immunotherapies represent the main therapeutic options for maintaining remission in Crohn’s, currently. But severe toxicities and poor patient compliance limit the long-term use for IV immunotherapies; therefore oral administration with take-home capsules of Foralumab is an attractive approach, as it could provide local action to treat gut inflammation. Oral capsules also provide the convenience of home use, and increase patient compliance by eliminating the need for infusions in a clinic or hospital setting.

“Previously, we reported that oral administration of Foralumab was well-tolerated and that the treatment did not result in severe toxicities that are so commonly observed with IV administration of anti-CD3 mAbs, suggesting that oral administration may be able to minimize toxicities and thereby improve clinical outcome. Our patent on the core formulation technologies covering alternative routes of administration for immunotherapies has been already granted in the U.S. and it is pending in other countries worldwide,” explained Dr. Kunwar Shailubhai, chief executive officer and chief scientific officer of Tiziana. “We believe switching to oral, nasal and inhalational administration of mAbs from the traditional intravenous administration could potentially be transformational for the future development of immunotherapies.”