Sulforadex (sulforafan alfadex) / Evgen Pharma, STALICLA - LARVOL DELTA

A Phase 1 Randomized, Placebo-Controlled Study Evaluating the Safety, Tolerability, and Pharmacokinetics of Enteric-Coated Stabilized Sulforaphane (SFX-01) in Male Participants. (PubMed, Adv Ther) - "This study demonstrated the safety and tolerability of SFX-01 over 7 days and indicated that the pharmacokinetic behavior of SFX-01 enteric-coated tablets was in line with expectations."

Clinical • Journal • P1 data • PK/PD data • Gastrointestinal Disorder • Oncology

A Randomised Controlled Trial of SFX-01 After Subarachnoid Haemorrhage - The SAS Study. (PubMed, Transl Stroke Res) - P2 | "SFN penetrated CSF less than expected and did not reduce large vessel vasospasm or improve outcome. Trial registration: NCT02614742 clinicaltrials.gov."

Journal • Inflammation • Subarachnoid Hemorrhage • GSTT1 • HP

Antitumour effects of SFX-01 molecule in combination with ionizing radiation in preclinical and in vivo models of rhabdomyosarcoma. (PubMed, BMC Cancer) - "In summary, our results provide evidence for the antitumour properties of SFX-01 in preclinical models of RMS tumours, both as a standalone treatment and in combination with irradiation. These forthcoming findings are crucial for deeper investigations of SFX-01 molecular mechanisms against RMS and for setting up clinical trials in RMS patients in order to use the SFX-01/IR co-treatment as a promising therapeutic approach, particularly in the clinical management of aggressive RMS disease."

Combination therapy • Journal • Preclinical • Oncology • Rhabdomyosarcoma • Sarcoma • Soft Tissue Sarcoma • Solid Tumor

SFX-01 in hospitalised patients with community-acquired pneumonia during the COVID-19 pandemic: a double-blind, randomised, placebo-controlled trial. (PubMed, ERJ Open Res) - "At days 8 and 15, respectively, 310 and 42 significant differentially expressed genes were identified between groups (false discovery rate adjusted p1). SFX-01 treatment did not improve clinical status or modulate key Nrf2 targets in patients with CAP primarily due to SARS-CoV-2 infection."

Journal • Infectious Disease • Novel Coronavirus Disease • Oncology • Pneumonia • Respiratory Diseases • IL1B • IL6

Positive update on SFX-01 in vitro GBM studies (Evgen Press Release) - "Evgen Pharma plc...announces that the laboratory of Dr Marjolein Geurts, neuro-oncologist at the Erasmus University Medical Centre has observed continuing activity of SFX-01 in GBM cells. The in vitro studies, which are supported by a grant awarded by the KWF Dutch Cancer Society for a €1.1m project, are designed to investigate the activity of SFX-01 in preclinical GBM models. This work is to be followed by administration of SFX-01 to patients with GBM in a clinical Investigator Sponsored Study (ISS)."

Preclinical • Brain Cancer • CNS Tumor • Glioblastoma • Oncology

Stable Sulforaphane Targets the Early Stages of Osteoclast Formation to Engender a Lasting Functional Blockade of Osteoclastogenesis. (PubMed, Cells) - "This aligned with data suggesting that SFX-01 reduced DC-STAMP levels, osteoclast nuclear number and modified cytoskeletal architecture. Pharmacological regulation of the NRF2 pathways, via selective inhibitors/activators, supported the anti-osteoclastogenic roles of an SFX-01-mediated by NRF2 activation, as well as the need for tight NF-KB pathway regulation in osteoclast formation/function."

Journal

Evgen Pharma plc - Final Clinical Study Report from Phase 1b PK/PD study of new SFX-01 tablet formulation approved (Market Screener) - P1b | N=NA | "Evgen Pharma plc...reports the final data from its Phase 1b healthy volunteer study using the Company's new enteric coated tablet formation of lead asset SFX-01....Additional pharmacodynamic exploratory investigation, utilising mRNA sequencing, showed changes in gene expression after dosing with SFX-01 even in healthy volunteers...The initial analysis identified a large number of significant differentially expressed genes in the SFX-01 treated group, between blood samples taken before the first dose was administered (baseline) and blood samples taken after the first dose timepoint (6 hours after first dose). Further analysis will be undertaken on this large and complex dataset to gain insight into the particular genes identified. Further disease-related mechanistic insight will also be provided from future clinical studies in patients."

P1 data • Brain Cancer • CNS Disorders • CNS Tumor • Glioblastoma • Glioma • Oncology • Solid Tumor

Evgen Pharma plc - Return of rights to Sulforadex from Juvenescence (Market Screener) - "Evgen Pharma plc...and partner JuvLife Ltd, a division of Juvenescence Ltd, have agreed to terminate the Patent and Know-How License Agreement for Evgen's Sulforadex sulforaphane stabilisation technology. The exclusive rights will be returned in Q4 2023. The upfront payment already received is non-refundable."

Licensing / partnership • Brain Cancer • Breast Cancer • CNS Disorders • CNS Tumor • Estrogen Receptor Positive Breast Cancer • Glioblastoma • Glioma • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor

Positive results for Evgen’s rhabdomyosarcoma therapy (PharmaTimes) - "Evgen Pharma – a company focusing sulforaphane-based therapies – has issued an update on its research partnership with Sapienza University of Rome, which has been concentrating on the radiosensitising impact of SFX-01 in-vivo when treating rhabdomyosarcoma (RMS)....The effects have now also been established in-vivo in a mouse xenograft model of RMS. Meanwhile, the impact of SFX-01 given orally on the growth of patient derived RMS tumour cells in-vivo, was also researched. Consequently, the therapy was effective at decreasing the growth of tumour masses when provided as a single agent in a daily basis. It was also given in combination with a radiotherapy regime, where it was shown to act synergistically, resulting in a more positive outcome than would be expected."

Preclinical • Oncology • Rhabdomyosarcoma • Sarcoma • Soft Tissue Sarcoma • Solid Tumor

Evgen Pharma obtains grant for glioblastoma studies in Netherlands (Proactiveinvestors) - "Evgen Pharma PLC...said its collaborator at the Erasmus University Medical Centre in the Netherlands has received a successful notice of a grant from the KWF Dutch Cancer Society for investigator-sponsored pre-clinical and clinical studies of SFX-01 in glioblastoma. The studies will cover the use of SFX-01 in pre-clinical glioblastoma models, followed by a clinical Investigator Sponsored Study (ISS) window-of-opportunity study in glioblastoma patients. The intention is to establish presence of the drug in human brain tumours and engagement with relevant molecular targets in excised tumour tissue."

Financing • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor

SFX-01 in the treatment of rhabdomyosarcoma: Preclinical results in cellular models (Sarcoma-RC 2023) - "SFX-01 and IR have strong cytotoxic effects and drastically inhibit the formation of cancer stem cell-derived tumorspheres, this indicating that the combined treatment might have therapeutic benefits, mainly in the clinical managements of patients with aggressive RMS disease. Legal entity responsible for the study The authors."

Preclinical • Oncology • Rhabdomyosarcoma • Sarcoma • Solid Tumor • CCNB1 • CCND1

Evgen notes evidence of radiosensitisation by SFX-01 in cancer cell (Market Screener) - P=N/A | N=N/A | “Evgen Pharma PLC said on Thursday it had found further evidence of radiosensitisation by SFX-01 in sarcoma cells. Evgen…said its evaluation of the anti-tumor activity of SFX-01 in two rhabdomyosarcoma (RMS) tumours showed that SFX-01 reduced tumour cell growth by triggering death damage in cancer cells….In addition, SFX-01 was shown to be effective both as a single agent and in combination with radiotherapy, while creating a more positive outcome than expected by adding the two agents together, Evgen said….Evgen's findings were in partnership with Sapienza University of Rome professor Francesco Marampon, who is part of its radiotherapy department. The company said the results will be presented at the ESMO Sarcoma and Rare Cancers Congress in Lugano, Switzerland, in late March.”

Clinical data • Oncology • Rhabdomyosarcoma • Sarcopenia • Soft Tissue Sarcoma • Solid Tumor

Regulatory approval received for Evgen’s SFX-01 study (PharmaTimes) - "Evgen...has received regulatory approvals for a healthy volunteer study to examine the performance of SFX-01. The lead asset therapy is the company’s new enteric coated tablet formulation....The phase 1/1b study will be a placebo-controlled, dose-escalating, randomised trial conducted in the UK. It is planned to start in the fourth quarter of 2022, with results expected in the first half of 2023."

New P1 trial • P1 data • Oncology

Stabilised, synthetic sulforaphane in hospitalized patients with suspected COVID-19 pneumonia: a double-blind, placebo-controlled RCT (ERS 2022) - "We investigated the efficacy of S-SFN (stabilised sulforaphane, activator of Nrf2) to improve clinical outcomes in patients hospitalized with suspected COVID-19...Adverse events were reported in 44.1% of placebo treated and 64.6% of S-SFN treated patients. Conclusions S-SFN treatment did not improve day 15 clinical status in hospitalized patients with suspected or confirmed COVID-19 infection."

Clinical • Infectious Disease • Novel Coronavirus Disease • Pneumonia • Respiratory Diseases • IL1B • IL6 • TNFA

High bone mass in mice can be linked to lower osteoclast formation, resorptive capacity, and restricted in vitro sensitivity to inhibition by stable sulforaphane. (PubMed, Cell Biochem Funct) - "In contrast, 10-fold higher SFX-01 concentrations were required for similar inhibition in CBA-derived cells and, strikingly, a further 2.5-fold greater concentration was required for significant restriction of osteoclast formation/function in STR/Ort. These data are consistent with the notion that the BM osteoclast precursor population contributes to the relative differences in mouse bone mass and that mice with higher bone mass exhibit lower in vitro osteoclastogenic potential as well as reduced sensitivity to inhibition by SFX-01."

Journal • Preclinical

Multiple Antitumor Molecular Mechanisms Are Activated by a Fully Synthetic and Stabilized Pharmaceutical Product Delivering the Active Compound Sulforaphane (SFX-01) in Preclinical Model of Human Glioblastoma. (PubMed, Pharmaceuticals (Basel)) - "SFX-01 deserves to be considered as an emerging anticancer agent for the treatment of GBM. The possible radio- and chemo sensitization potential of SFX-01 should also be evaluated in further preclinical and clinical studies."

Journal • Preclinical • Brain Cancer • Glioblastoma • Glioma • Immunology • Oncology • Solid Tumor • HIF1A • STAT3

Final results of the STEM trial: SFX-01 in the treatment and evaluation of ER+ Her2- metastatic breast cancer (mBC) (ESMO 2019) - P2; "In preclinical models SFX-01 inhibits the activity of cancer stem-like cells and reverses resistance to endocrine therapies (ET) tamoxifen (Tam) and fulvestrant (Fulv). SFX-01 300 mg BID was safe and well tolerated in patients with ER+ and HER2- mBC. SFX-01 in combination with ET demonstrated anti-tumour activity and prolonged disease stabilisation in pre-treated patients who were progressing on the background ET at study entry. Further development of SFX-01 in ER+ mBC is warranted."

Clinical

Evgen Pharma recruits over 100 patients into COVID-19 trial (PharmaTimes) - "UK-based Evgen Pharma has announced that it has now recruited a total of 102 patients into a trial investigating its lead asset SFX-01 in COVID-19. The Phase II/III STAR trial is investigating if SFX-01 can reduce the severity or prevent the onset of acute respiratory distress syndrome (ARDS) in patients with suspected COVID-19....Evgen is expecting recruitment to the STAR trial to be completed at the end of 2021 or the first quarter of 2022."

Enrollment status • Infectious Disease • Novel Coronavirus Disease

SFX-01 treatment for Acute Respiratory Infections (STAR-Covid19) (clinicaltrialsregister.eu) - P2; N=300; Sponsor: University of Dundee

Clinical • New P2 trial • Infectious Disease • Novel Coronavirus Disease • Pneumonia • Respiratory Diseases

Targeting STAT3 signaling using stabilised sulforaphane (SFX-01) inhibits endocrine resistant stem-like cells in ER-positive breast cancer. (PubMed, Oncogene) - "Both tamoxifen and fulvestrant increased MFE and aldehyde dehydrogenase (ALDH) activity of patient-derived xenograft (PDX) tumors, which was reversed by combination with SFX-01. Increased expression of these genes after 3 months' endocrine treatment of ER+ patients (n = 68) predicted poor prognosis. Our data establish the importance of STAT3 signaling in CSC-mediated resistance to endocrine therapy and the potential of SFX-01 for improving clinical outcomes in ER+ breast cancer."

Journal • Breast Cancer • Estrogen Receptor Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • MUC1

Study protocol for SFX-01 after subarachnoid haemorrhage (SAS): a multicentre randomised double-blinded, placebo controlled trial. (PubMed, BMJ Open) - P2; "Outcomes of the trial will be submitted for publication in a peer-reviewed journal. NCT02614742."

Clinical • Journal • HP • MRI

SFX-01 After Subarachnoid Haemorrhage (clinicaltrials.gov) - P2; N=90; Completed; Sponsor: Evgen Pharma; Active, not recruiting ➔ Completed

Trial completion • HP

Evgen Pharma, University Of Dundee to collaborate to advance SFX-01 trials (Morningstar.com) - "Drug development company, Evgen Pharma PLC on Thursday entered a Memorandum of Understanding with University of Dundee's School of Medicine agreeing to work together using MRI scanning technology to investigate the efficacy of drug SFX-01 in reversing the signs of non-alcoholic steatohepatitis (NASH) and liver fibrosis."

Clinical

Evgen Pharma upbeat on latest news from SFX-01 studies (Sharecast) - "Clinical stage drug development company Evgen Pharma announced on Monday that five patients who participated in the ‘STEM’ trial received ‘SFX-01’ treatment for more than one year, with two of those patients continuing to be treated with SFX-01....Of the two patients continuing to be treated with SFX-01, one had now reached 438 days of dosing, and the other 476 days, with the latter exceeding the previous best of 448 days."

Trial status

Evgen Pharma receives last patient for stroke treatment drug trial (Morningstar.com) - "Evgen Pharma PLC said Wednesday it has entered its last patient in the double-blind, placebo-controlled SAS Phase II clinical trial that is testing its SFX-01 product, aimed at improving the treatment of strokes."

Enrollment status