On January 4, 2022 Soligenix, Inc. (Nasdaq: SNGX) (Soligenix or the Company), a late-stage biopharmaceutical company focused on developing and commercializing products to treat rare diseases where there is an unmet medical need, reported that dusquetide is effective at reducing tumor size in nonclinical xenograft models. Recent studies, recapitulating results from previously published studies, have confirmed the efficacy of dusquetide as a stand-alone and combination anti-tumor therapy, with radiation, chemotherapy and targeted therapy, in the context of the MCF-7 breast cancer cell line (Press release, Soligenix, JAN 4, 2022, View Source [SID1234598096]). Dusquetide previously demonstrated benefits in reducing the duration of severe oral mucositis (SOM) in a Phase 2 clinical trial and reduction in SOM rates in the per protocol population in a Phase 3 study. In addition to the reduction of severe oral mucositis, an acceleration in the clearance of tumor response and an increase in overall survival were also observed in the Phase 2 clinical study as an ancillary benefit to treating oral mucositis in patients receiving chemo-radiation for their head and neck cancer (HNC).
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Based on the biological proof of principle shown both nonclinically and clinically with dusquetide, a novel synthetic peptide that modulates the body’s innate immune system, Soligenix continues to explore product opportunities, both in the reduction of oral mucositis in HNC and as a potential anti-cancer treatment. Dusquetide binds to p62 or SQSTM-1, a scaffold protein implicated in a number of intracellular signaling networks implicated in tumor cell survival, including autophagy. The role of p62 is best characterized in multiple myeloma and breast cancer. All variants of breast cancer, including metastatic breast cancer, estrogen receptor positive (ER+), human epidermal growth factor receptor 2 high expressing (HER2+) and triple negative expressing cell lines, have demonstrated a significant role for p62 in tumorigenesis.
The MCF-7 cell line tested in the xenograft studies with dusquetide is both ER+ and responsive to anti-HER2 treatment. Treatment with dusquetide was effective not only as a stand-alone treatment (p<0.01 for tumor size), but also in conjunction with radiation (p<0.05 vs radiation only for survival), chemotherapy (paclitaxel) and targeted treatment (trastuzumab; p<0.001 vs. placebo only for tumor size), reducing tumor size and enhancing overall survival. Other tumor types also have been shown to be dependent on p62 expression, including multiple myeloma, liver cancer (hepatocellular carcinoma), lung cancer (non-small cell lung cancer, EGFR-TKI-resistant lung cancer), intestinal cancer (small intestinal adenocarcinoma and gastric cancer), and colorectal cancer and ovarian cancer (multi-drug resistant).
"Soligenix continues to pursue potential product opportunities with our new chemical entity dusquetide, including in oncology," stated Christopher J. Schaber, PhD, President and Chief Executive Officer of Soligenix. "With the supportive data from the Phase 2 and 3 oral mucositis trials, and the nonclinical anti-tumor efficacy demonstrated, we continue to pursue potential partnership for this novel molecule."
About Dusquetide
Dusquetide (the active ingredient in SGX942) is an innate defense regulator (IDR), a new class of short, synthetic peptides. It has a novel mechanism of action whereby it modulates the body’s reaction to both injury and infection towards an anti-inflammatory, anti-infective and tissue healing response. IDRs have no direct antibiotic activity but, by modulating the host’s innate immune system responses, increase survival after infections caused by a broad range of bacterial Gram-negative and Gram-positive pathogens. It also accelerates resolution of tissue damage following exposure to a variety of agents including bacterial pathogens, trauma and chemo- and/or radiation therapy. Preclinical efficacy and safety has been demonstrated in numerous animal disease models including mucositis, colitis, macrophage activation syndrome (MAS) as well as bacterial infections, including melioidosis. Potential anti-tumor activity has been demonstrated in in vitro and in vivo xenograft studies.
SGX942 has demonstrated safety and tolerability in a Phase 1 clinical study in 84 healthy human volunteers. Positive efficacy results were demonstrated in an exploratory Phase 2 clinical study (Study IDR-OM-01) in 111 patients with oral mucositis due to CRT for HNC, including potential long term ancillary benefits. The Phase 3 multinational, placebo-controlled, randomized study evaluated the impact of dusquetide on the duration of SOM in 268 subjects with squamous cell carcinoma of the oral cavity and oropharynx, scheduled to receive a minimum total cumulative radiation dose of 55 Gy with concomitant cisplatin chemotherapy. A clinically meaningful reduction in the duration of SOM was observed in the ITT population and a clinically and statistically significant reduction was observed in the per protocol population.
SGX942 has received Fast Track Designation from the FDA for the treatment of oral mucositis as a result of radiation and/or chemotherapy treatment in HNC patients, as well as Promising Innovative Medicine designation in the United Kingdom by the Medicines and Healthcare products Regulatory Agency for the treatment of severe oral mucositis in HNC patients receiving CRT. In addition, products containing the same active ingredient, dusquetide, have been granted Fast Track Designation as an adjunctive therapy with other antibacterial drugs, for the treatment of melioidosis and Orphan Drug Designations in the treatment of MAS and the treatment of acute radiation syndrome.
Soligenix has a strong intellectual property position in the IDR technology platform, including composition of matter for dusquetide and related analogs. Dusquetide was developed pursuant to discoveries made by Professors B. Brett Finlay, PhD and Robert Hancock, PhD of the University of British Columbia, Canada. Soligenix has received partial funding from NIH for its oral mucositis clinical studies. The Phase 2 study was supported with a Phase I SBIR grant (#R43DE024032) award, with the Phase 3 study being supported by a Phase II SBIR grant (#R44DE024032) award.
In addition, a high level review of the IDR technology platform is available here.