Immutep Announces Discontinuation of Phase 2 Ulcerative Colitis Study by GSK

On January 22nd, Immutep Limited announced the discontinuation of Phase 2 clinical trial by its licensing partner, GlaxoSmithKline (GSK). The trial evaluated the anti-LAG3 cell depleting monoclonal antibody, GSK2831781, in patients with active ulcerative colitis (inflammatory bowel disease (IBD) causing ulcers (sores) in the digestive tract).

The antibody was derived from IMP731 and licensed to GSK in 2010. GlaxoSmithKline stopped the trial based on the assessment of clinical data as part of a planned interim analysis conducted in consultation with the trial’s Data Review Committee.

Trial Structure

Approximately 242 participants were included in the multicenter, randomized, double-blind, placebo-controlled study. The trials investigated the safety, tolerability, efficacy, and dose-responsiveness of GSK2831781 in participants with moderate to severe active ulcerative colitis. The study consisted of a 5-week screening window, 10-week Induction Phase, 30-week double-blind Extended Treatment Phase (ETP), and 42-week Follow-Up Phase.

GSK2831781

GSK2831781 was developed by Immutep to treat autoimmune disease by targeting LAG-3+ (T-cell activation market) activated T cells that are known to accumulate at the diseased organ site.

The drug destroys the T cells through ADCC (antibody-dependent cellular cytotoxicity) and CDC (complement-dependent cytotoxicity) and removes them from the body.

GSK2831781 is considered by some to be the next wave of autoimmune system treatments. Unlike TNF monoclonal antibodies or corticosteroids. Treatments like GSK2831781 deplete the few activated auto-aggressive T cells rather than just treat the symptoms of autoimmune disorders.

The discontinued trial was intended for ulcerative colitis, but GSK2831781 has other applications. Immutep noted that GSK2831781 has also been explored in another autoimmune disease beyond ulcerative colitis. The drug was evaluated in a phase I study with psoriasis. The trial showed preliminary evidence of clinical efficacy.

Immutep Pipeline

Despite the setback, Immutep still has three product candidates, all of which rely on a different mechanism of action from GSK2831781. The first of these is eftilagimod alpha (known as efti or IMP321) and is currently being evaluated in Active Immunotherapy PAClitaxel (AIPAC) Immutep’s largest clinical trial.

The Phase IIb trial evaluates the use of eftilagimod alpha as immunotherapy with taxane-based chemotherapy called paclitaxel in patients with hormone receptor-positive metastatic breast cancer (MBC). This treatment is intended to boost the immune response against tumor cells compared to chemotherapy alone.

Second is Two ACTive Immunotherapies-002 (TACTI-002) that evaluates the combination of efti with MSD’s KEYTRUDA® (or pembrolizumab, an anti-PD-1 therapy) for up to 109 patients.

Two ACTive Immunotherapeutics in melanoma (TACTI-mel) is a Phase I safety and dose-finding clinical trial of efti given in combination with pembrolizumab (Keytruda) in patients with locally advanced or metastatic melanoma. The study combined two immunotherapies to enhance the immune response by activated T cells.

Financial Impact

Despite the clinical trial’s discontinuation, Immutep’s collaboration with GSK endures, and GSK2831781 continues to be under an exclusive license with GSK. As part of the collaboration agreement with GSK, Immutep is eligible to receive up to 54 million pounds in developmental milestone payments and single-digit tiered royalties if GSK2831781 is commercialized.

Further milestone payments are subject to the continuation of the program, while GSK is responsible for all costs associated with the clinical development and commercialization of GSK2831781.

In addition, there is no impact on Immutep’s funding capacity for the development of its in-house programs. Immutep said it remains in a robust operational and financial position with a cash runway beyond the end of the calendar year 2022. The most recent fundraising round for Immutep was for equity in 2019 and raised 10 million Australian dollars for their publically traded company.

Related Article: Bristol Myers Squibb’s Zeposia Shines in Ulcerative Colitis Trial

References

1. https://www.globenewswire.com/news-release/2021/01/21/2162573/0/en/Ulcerative-Colitis-Phase-II-Study-of-GSK2831781-Discontinued.html

Author

Eduardo Longoria