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  • For the treatment of Immune Checkpoint Inhibitor (ICI)-associated colitis and diarrhea to enable oncology patients to stay on treatment

FW-420 is a niclosamide-based, small molecule anti-inflammatory inhibitor therapy for the treatment of immune checkpoint inhibitor (ICI)-associated colitis and diarrhea in metastatic cancer patients.  FW-420 will be supplied in two formulations, as an oral immediate-release tablet and as a topical rectal enema foam made from milled (micronized) niclosamide.

The standard care for treating inflammatory bowel diseases (IBD), such as ulcerative colitis and Crohn’s Disease, are corticosteroids and 5-ASAs.  These medications, unfortunately, can cause problems when used by check point inhibitor patients due to their immunosuppressant effects.

FW-420 has the potential to safely treat grade 1 ICI-associated colitis and diarrhea and prevent its progression to more serious and potentially fatal later stages. The goal of early treatment with niclosamide is to enable cancer patients to continue their ICI treatment programs without or with minimal interruption.

About Niclosamide

Niclosamide is a prescription small molecule drug listed as an essential medicine by the World Health Organization (WHO). Niclosamide has been safely used by millions of patients for other clinical indications.  In the U.S., niclosamide was approved by the U.S. Food and Drug Administration (FDA) in 1982 for the treatment of intestinal tapeworm infections. In addition to its anthelminthic activity, niclosamide has demonstrated anti-inflammatory and anti-viral properties.

Click through to indication:

Immune Checkpoint Inhibitor-Associated Colitis

Immune checkpoint inhibitors (ICIs) are monoclonal antibodies that have revolutionized the treatment of a variety of malignancies by targeting down-regulators of the anti-cancer immune response.. The global market of immune checkpoint inhibitors (ICIs) is significant; it was over $22 billion in 2019 and growing rapidly.¹ Approximately 44% of patients with advanced cancer tumors (more than 260,000 patients) are eligible to receive ICIs.²

However, many immune-related adverse events, especially diarrhea and colitis, limit their use.  The incidence of immune-mediated colitis (IMC) ranges from 1% to 25% depending on the type of ICI and whether they are used in combination used in combination.² Approximately 30% of ICI patients develop diarrhea, which can progress to colitis.

The onset of diarrhea in ICI-AC patients occurs within 6-7 weeks and progressively worsens, and the progression to colitis is rapid and unpredictable. For example, in patients taking ipilimumab (Yervoy), between 25% and 30% of patients developed diarrhea and roughly 8% to 12% developed colitis.³ Moreover, the trend is towards the use of combination ICI therapies (e.g., Yervoy and Opdivo) and this could lead to a concomitant increase in both diarrhea and colitis.

Administration of corticosteroids, or treatment with certain immunosuppressive biologics, while withholding ICI therapy are recommended for grade 2 or more severe colitis (National Cancer Institute 2020).  The impact of this colitis complication and treatment may reduce the goal of progression free cancer survival. An oral, non-absorbed treatment, such as niclosamide, for grade 1 colitis (diarrhea) may prevent progression to grade 2 disease. There currently is no approved treatment for grade 1 colitis. FW-420 has the potential for accelerated regulatory approval through a breakthrough designation.

References

1) Immune Checkpoint Inhibitors Market, ResearchAndMarkets.com, 2020
2) Wang et al. Patients with ICPI-induced diarrhea or colitis have improved survival outcomes. J Immunother Cancer. 2018; 6: 37. Som et al., World J Clin Cases. Feb 26, 2019; 7(4): 405-418
3) Wang DY, Ye F, Zhao S, et al. Incidence of immune checkpoint inhibitor-related colitis in solid tumor patients: a systematic review and meta-analysis. Oncoimmunology 2017; 10: e1344805; Som et al., World J Clin Cases. Feb 26, 2019; 7(4): 405-418