dusquetide (SGX942) / Soligenix - LARVOL DELTA

Dusquetide Regulates SQSTM1/p62-Mediated Mitophagy to Alleviate PM2.5-Aggravated Airway Inflammation in Asthma. (PubMed, Zhongguo Yi Xue Ke Xue Yuan Xue Bao) - "Results PM2.5 exposure enhanced airway hyperresponsiveness (P<0.01),exacerbated inflammation and mucus secretion (P<0.01),and increased TOMM20 and LC3B co-localization signals (P<0.01) in HDM-sensitized mice.Mdivi-1 inhibition of mitophagy reduced inflammation (P<0.01).Mitochondrial proteomics identified SQSTM1/p62 as a core regulatory factor,whose expression was up-regulated after PM2.5 exposure (P<0.01).Dusquetide intervention inhibited SQSTM1/p62 function and mitophagy (P<0.01),reduced airway hyperresponsiveness in mice of the HP group (P<0.01),and alleviated inflammatory manifestations (P<0.01). Conclusion PM2.5 exacerbates HDM-induced asthma pathology by activating SQSTM1/p62-mediated mitophagy,while dusquetide effectively alleviates this process,demonstrating the potential as a therapeutic target for PM2.5-related asthma."

Journal • Asthma • Immunology • Inflammation • Pulmonary Disease • Respiratory Diseases • SQSTM1

Soligenix Receives Orphan Drug Designation from the European Commission for SGX945 for the Treatment of Behçet's Disease (PRNewswire) - "...following review of the recently published Phase 2a clinical results demonstrating biological efficacy and safety in patients with Behçet's Disease. SGX945 has previously been granted both orphan drug and fast track designations from the U.S. Food and Drug Administration (FDA) for the treatment of Behçet's Disease."

Orphan drug • Rare Diseases

Soligenix Announces SGX945 Receives Promising Innovative Medicine Designation from the UK Medicines and Healthcare Products Regulatory Agency (PRNewswire) - "'We are excited that the MHRA agrees that dusquetide meets the specified criteria for PIM designation based on the Phase 2 clinical data in Behçet's Disease, in conjunction with the consistency that has been observed in previous clinical studies in oral mucositis,' stated Christopher J. Schaber, PhD, President and Chief Executive Officer of Soligenix."

European regulatory • Inflammation • Rare Diseases

Soligenix Receives Positive Opinion from the European Medicines Agency on the Request for Orphan Drug Designation for SGX945 for the Treatment of Behçet's Disease (PRNewswire)

Orphan drug • Inflammation • Rare Diseases

Results from a pilot study of dusquetide for the treatment of aphthous ulcers associated with Behçet syndrome. (PubMed, Rheumatology (Oxford)) - P2 | "This small pilot study illustrates the potential efficacy and tolerability of SGX945 in patients with Behçet's syndrome who had ulcers despite being on colchicine maintenance therapy. The results justify further development of SGX945 for the treatment of Behçet's syndrome."

Journal • Pain • Rare Diseases

Dusquetide for the Treatment of Behcet's Disease (clinicaltrials.gov) - P2 | N=8 | Completed | Sponsor: Soligenix | Recruiting ➔ Completed | N=25 ➔ 8

Enrollment change • Trial completion • Immunology • Rare Diseases

FDA Grants Soligenix Orphan Drug Designation for the Treatment of Behçet's Disease after Reviewing Recent Phase 2 Clinical Study Results (PRNewswire)

Orphan drug • Rare Diseases

Soligenix Announces Recent Accomplishments And First Quarter 2025 Financial Results (PRNewswire) - "Furthermore, we expect to report top-line results in the second half of this year from our ongoing Phase 2 studies of SGX945 (dusquetide) in Behçet's disease and SGX302 (synthetic hypericin) in mild-to-moderate psoriasis..."

P2 data • Psoriasis

Dusquetide for the Treatment of Behcet's Disease (clinicaltrials.gov) - P2 | N=25 | Recruiting | Sponsor: Soligenix | Trial completion date: Apr 2025 ➔ Aug 2025 | Trial primary completion date: Mar 2025 ➔ Jul 2025

Trial completion date • Trial primary completion date • Immunology • Rare Diseases

Dusquetide for the Treatment of Behcet's Disease (clinicaltrials.gov) - P2 | N=25 | Recruiting | Sponsor: Soligenix | Not yet recruiting ➔ Recruiting | Initiation date: Jul 2024 ➔ Nov 2024

Enrollment open • Trial initiation date • Immunology • Rare Diseases

Comparisons of successful and failed Phase III trials of drugs and biologicals tested for mitigation of oral mucositis in patients being treated with radiotherapy with or without concomitant chemotherapy for cancers of the head and neck. (PubMed, Drug Dev Res) - "Of the three successful Phase III trials, one investigated avasopasem manganese (Galera Therapeutics) and two examined palifermin (Amgen). The three failed trials included those evaluating dusquetide (Soligenix), iseganan hydrochloride (IntraBiotics Pharmaceuticals), and clonidine (Monopar Therapeutics). We found that differences in the level of sponsor funding, patient inclusion criteria including radiation source and concomitant chemotherapy regimen, and concordance of primary efficacy outcomes between Phase II and Phase III trials influenced outcomes. To properly design clinical trials for OM in HNC patients, it is important that researchers and sponsors take note of specific study characteristics associated with success or failure, particularly with Phase III trials where the risks and costs are the highest."

Clinical • Journal • P3 data • Head and Neck Cancer • Mucositis • Oncology • Oral Cancer • Solid Tumor • Stomatitis

Dusquetide for the Treatment of Behcet's Disease (clinicaltrials.gov) - P2 | N=25 | Not yet recruiting | Sponsor: Soligenix

New P2 trial • Immunology • Rare Diseases

Linker-Free Synthesis of Antimicrobial Peptides Using a Novel Cleavage Reagent: Characterisation of the Molecular and Ionic Composition by nanoESI-HR MS. (PubMed, Pharmaceutics) - "The novel methodology was successful in synthesising three antimicrobial peptides, including the cyclic compound polymyxin B3, dusquetide, and RR4 heptapeptide. Furthermore, electrospray mass spectrometry (ESI-MS) is successfully used for the full characterisation of both the molecular and ionic composition of the synthetic peptides."

Journal

Protocol to identify drug-binding sites in proteins using solution NMR spectroscopy. (PubMed, STAR Protoc) - "Dusquetide is a next-generation IDR (innate defense regulator) targeting the major autophagy receptor protein SQSTM1/p62 and modulating the innate immune response...For complete details on the use and execution of this protocol, please refer to Zhang et al. (2022)."

Journal • SQSTM1

DOM-INNATE: Study of SGX942 for the Treatment of Oral Mucositis in Patients With Concomitant Chemoradiation Therapy for Head and Neck Cancer (clinicaltrials.gov) - P3 | N=266 | Completed | Sponsor: Soligenix | Active, not recruiting ➔ Completed

Trial completion • Head and Neck Cancer • Mucositis • Oncology • Oral Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Stomatitis

Dusquetide modulates innate immune response through binding to p62. (PubMed, Structure) - "Dusquetide binding modulates the p62-RIP1 complex, increases p38 phosphorylation, and enhances CEBP/B expression without activating autophagy. Our findings provide molecular details underlying the IDR action that may help in the development of new strategies to pharmacologically target p62."

Journal • CEBPA • RIPK1 • SQSTM1

"$SNGX Key Binding Characteristics of Dusquetide to Important Intracellular Protein Identified https://t.co/jqqLcBTizZ" (,@stock_titan)

Dusquetide Demonstrates Positive Anti-tumor Efficacy in Multiple Nonclinical Animal Studies (PRNewswire) - "Soligenix, Inc...announced...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."

Breast Cancer • Oncology • Solid Tumor

Soligenix Announces Topline Results from its Phase 3 Clinical Trial of SGX942 for the Treatment of Oral Mucositis in Head and Neck Cancer Patients (PRNewswire) - P3, N=268; DOM-INNATE (NCT03237325); Sponsor: Soligenix; "The primary endpoint of median duration of SOM did not achieve the pre-specified criterion for statistical significance (p≤0.05); although biological activity was observed with a 56% reduction in the median duration of SOM from 18 days in the placebo group to 8 days in the SGX942 treatment group. Despite this clinically meaningful improvement, the variability in the distribution of the data yielded a p-value that was not statistically significant."

P3 data: top line • Mucositis • Oncology • Squamous Cell Carcinoma of Head and Neck

Soligenix Announces $20 Million Strategic Convertible Debt Financing Agreement with Pontifax Medison Debt Financing (PRNewswire) - "Soligenix, Inc...announced today that it has entered into a $20 million convertible debt financing agreement with Pontifax Medison Debt Financing (Pontifax)...'The access to less dilutive capital provided by this facility is designed to increase our financial flexibility as we continue to advance our rare disease pipeline, and build toward commercialization in the United States with SGX301 for the treatment of cutaneous T-cell lymphoma (CTCL) and SGX942 for the treatment of oral mucositis in head and neck cancer patients'..."

Financing • Cutaneous T-cell Lymphoma • Hematological Malignancies • Non-Hodgkin’s Lymphoma • Oncology

Soligenix Announces Phase 3 FLASH Study Continues to Demonstrate Positive Benefits in Patients with Cutaneous T-Cell Lymphoma (PRNewswire) - P3, N=169; FLASH (NCT02448381); Sponsor: Soligenix; "This data reinforces the positive SGX301 primary endpoint treatment response demonstrated in Cycle 1. SGX30l treatment in Cycle 3 further improved response rates, with 49% of patients electing to receive SGX301 for a total of 18 weeks demonstrating a 50% or greater reduction in their combined CAILS (Composite Assessment of Index Lesion Score) lesion score compared to 40% of patients demonstrating such a reduction after completing 12 weeks of SGX301 treatment in Cycle 2 (p=0.046)....'we now focus on our next near-term and potentially transformational catalyst - the announcement of top-line final results by year-end from our other pivotal Phase 3 study of SGX942 (dusquetide) for the treatment of oral mucositis in head and neck cancer patients.'"

P3 data • P3 data: top line • Cutaneous T-cell Lymphoma • Head and Neck Cancer • Hematological Malignancies • Mycosis Fungoides • Non-Hodgkin’s Lymphoma • Oncology • Squamous Cell Carcinoma of Head and Neck

DOM-INNATE: Study of SGX942 for the Treatment of Oral Mucositis in Patients With Concomitant Chemoradiation Therapy for Head and Neck Cancer (clinicaltrials.gov) - P3; N=268; Active, not recruiting; Sponsor: Soligenix; Recruiting ➔ Active, not recruiting

Clinical • Enrollment closed • Head and Neck Cancer • Mucositis • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Stomatitis

Soligenix Completes Enrollment in its Pivotal Phase 3 Clinical Trial of SGX942 for the Treatment of Oral Mucositis (PRNewswire) - "Soligenix, Inc…announced today it has completed patient enrollment in its Phase 3 DOM-INNATE ('Dusquetide treatment in Oral Mucositis – by modulating INNATE Immunity') study for SGX942 (dusquetide) in the treatment of oral mucositis (OM) in head and neck cancer (HNC) patients. The study successfully enrolled 268 subjects, following positive interim analysis, which included a prospectively defined, unblinded assessment of the study's primary efficacy endpoint by an independent Data Monitoring Committee (DMC). With enrollment completed, top-line results are expected in the fourth quarter of 2020."

Enrollment closed • P3 data: top line • Head and Neck Cancer • Mucositis • Oncology

A Dose Escalating Study of SGX942 for Oral Mucositis in Patients With Head and Neck Cancer (clinicaltrials.gov) - P2; N=78; Active, not recruiting; Sponsor: Soligenix; Recruiting ➔ Active, not recruiting

Enrollment closed • Biosimilar • Head and Neck Cancer • Immunology • Inflammation • Oncology

Soligenix announces recent accomplishments and year-end 2019 financial results (PRNewswire) - ‘”We are extremely pleased to have achieved positive top-line results in our pivotal Phase 3 FLASH (Fluorescent Light Activated Synthetic Hypericin) trial that demonstrates SGX301's potential to be an important new treatment for early stage cutaneous T-cell Lymphoma…we will now look to report results from the extended treatment portion of the trial, which we anticipate announcing in June 2020…we have successfully achieved our target of 260 patients randomized into the pivotal Phase 3 clinical trial of SGX942 (dusquetide) for the treatment of oral mucositis in patients with head and neck cancer (HNC) receiving chemoradiation therapy…Therefore, the study target to complete enrollment and provide top-line results is being revised from the second quarter of 2020 to the fourth quarter 2020…”

Enrollment status • P3 data: top line