On April 28, 2021 Race Oncology Limited ("Race") reported that it has entered into a collaborative preclinical research program with The University of Newcastle to investigate the heart safety Bisantrene offers over current anthracycline therapeutics (Press release, Race Oncology, APR 28, 2021, View Source [SID1234579463]). Eminent cardiotoxicity researchers, Associate Professors Aaron Sverdlov and Doan Ngo of the University of Newcastle, will lead the project.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

While Bisantrene’s heart safety has been demonstrated in more than 40 clinical trials, exactly how it avoids causing cardiotoxicity is unknown. Advances in molecular biology since the 1980s now allow the underlying mechanism of action to be determined. The aim of this project is to explore Bisantrene’s low cardiotoxicity at the molecular level. Bisantrene has recently been identified as a targeted inhibitor of the Fatso/Fat mass and obesity-associated protein (FTO)1. The possible role of FTO inhibition in Bisantrene’s lack of cardiotoxicity will be a primary focus of this research project.

Pillar 2 of Race’s Three Pillar strategy (ASX Announcement: 30 Nov 2020) is focused on the potential for Bisantrene to act as an anthracycline replacement, which are commonly used in the treatment of breast cancer. Anthracyclines are a class of chemotherapeutics known to be effective, but also cardiotoxic. The results of this study will support Phase IIb human trials of a Bisantrene in anthracycline naïve breast cancer patients. These trials are currently being explored for feasibility in Europe, with a potential for initiation in 2022.

"This is an exciting development for Race and we are looking forward to collaborating with Assistant Professors Sverdlov and Ngo on this important project. Understanding how Bisantrene works at a molecular level to avoid damage to the heart will aid all our clinical plans."

Chief Scientific Officer, Dr Daniel Tillett
This preclinical study is to start immediately with result to be reported over the coming 12 months.

About Associate Professors Aaron Sverdlov and Doan Ngo
Associate Professors Sverdlov and Ngo lead the dedicated Australian-first, bench-to- bedside "Cancer and the Heart" clinical and research program at University of Newcastle, Hunter Medical Research Institute, Hunter New England Local Health District and Calvary Mater Newcastle Hospitals. This program incorporates basic mechanistic discovery studies looking at mechanisms of cardiotoxicity, drug discovery studies, translational human research, clinical research and clinical inpatient and outpatient service delivery.

In recognition of this important initiative, A/Prof Aaron Sverdlov was awarded the 2018 Ministerial Award for Rising Stars in Cardiovascular Research. A/Prof Doan Ngo, a co- lead of the program was awarded NSW Health EMC Fellowship in Cardio-Oncology (2018-2021) and the highly prestigious National Heart Foundation Future Leader Fellowship (2021-2025) for the cardio-oncology program of work.

Both A/Profs Aaron Sverdlov and Doan Ngo have been invited to establish and co-chair the National Cardio-Oncology Working Group under the auspices of the Australian Cardiovascular Alliance (ACvA). The aim of the group is to coordinate clinical and research activities in the field of Cardio-Oncology in Australia and act as a scientific and advocacy body to improve the quality of cardiovascular care for our cancer patients.

Associate Professor Sverdlov has over 50 peer-reviewed publications and 4 book chapters (including chapters on Oxidative Stress in Heart Failure in the textbook "Heart Failure: A Companion to Braunwald’s Heart Disease") with over 1100 citations and has had more than 80 presentations at international and national meetings. He received over 30 competitive grants, with >20 in the last 5 years (total >$2.5M AUD).

Associate Professor Ngo is an academic pharmacist and a successful basic and translational scientist with multiple important contributions in the cardiovascular and metabolic field. She has more than 55 publications, of which more than 40 were published in the last 5 years

On April 28, 2021 OmniSeq, an innovator in next generation sequencing in oncology, reported the New York State Department of Health’s Clinical Laboratory Evaluation Program has approved the OmniSeq INSIGHTSM test (Press release, OmniSeq, APR 28, 2021, View Source,the%20OmniSeq%20INSIGHTSM%20test.&text=OmniSeq%20INSIGHT%20is%20a%20tissue%2Dbased%2C%20next%20generation%20sequencing%20test. [SID1234579250]). The test detects genomic variants, genomic signatures, and immune gene expression, providing physicians with clinically actionable evidence to inform therapeutic treatment decisions and identify potential clinical trial options for patients with late-stage solid tumor cancers.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The test will be commercially available to U.S.-based clinicians exclusively through Labcorp and globally to biopharmaceutical companies through Labcorp Drug Development. Throughout Canada, the test will be available through Dynacare, a Labcorp company.

"The launch of OmniSeq INSIGHT represents the continued evolution of our commitment to innovation and to the delivery of the most advanced, comprehensive solid tumor profiling assay," said Margot Schoenborn, Chief Executive Officer, OmniSeq. "It is designed to detect and characterize the genomic and immune features of patients’ cancer tumors to quickly guide more precise, individualized treatment decisions for patients to ensure they receive the best personalized medicine options available."

OmniSeq INSIGHT is a tissue-based, next generation sequencing test. It has been clinically and analytically validated for all solid tumors, interrogating gene alterations that are targets identified for therapy. Completely unique to the test is the integration of immune expression profiling, which detects genes involved in the anti-cancer immune response and tumor-immune mechanisms including low-expressing genes involved in inflammatory signaling. The combined profiling of molecular and immune genes delivers an unparalleled and powerful new tool to help physicians more effectively select personalized therapies and immunotherapies, as well as match patients to clinical trials based on multi-immune marker analyses.

OmniSeq INSIGHT delivers the distinct advantage of leveraging three technologies to better inform physicians in selecting the most appropriate therapies or clinical trials for their patients. DNA sequencing is used to detect base substitutions, insertions, deletions, copy number alterations, tumor mutational burden and microsatellite instability. RNA sequencing is employed for detection of known and novel gene arrangements in order to maximize detection of fusion events and gene expression profiling; this also provides differentiating insight into critical tumor-immune interactions. Additionally, PD-L1 expression is measured by immunohistochemistry using FDA-approved assays based on the tumor type tested.

OmniSeq INSIGHT can be used in both diagnostic and drug development settings. It is actively integrated into numerous drug development programs and can be configured as an effective discovery tool, screening tool or clinical trial assay and can drive companion diagnostics development and commercialization initiatives. OmniSeq INSIGHT is offered to global biopharmaceutical customers directly and through Labcorp Drug Development, which collectively have an extensive track record in validating assays across key regulatory standards, including CLIA, CLEP, CE-IVD and FDA under an ISO 13485 quality management system for medical devices.

On April 28, 2021 1 Redx Pharma (AIM: REDX), the drug discovery and development company focused on cancer and fibrosis, reported that it has successfully initiated dosing of the first patient cohort with a combination of RXC004, the Company’s lead drug candidate, and nivolumab (OPDIVO-Bristol Myers Squibb, an anti-PD-1 antibody) (Press release, Redx Pharma, APR 28, 2021, View Source [SID1234579170]). RXC004 is also currently being evaluated as monotherapy in a Phase 1 clinical study, from which top line results are expected by mid 2021.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The primary objective of the Phase 1 combination study is to evaluate the safety and tolerability of RXC004 in combination with nivolumab in patients with advanced malignancies (ClinicalTrials.gov Identifier:NCT03447470). The announcement today confirms that the first three patients have initiated treatment with 1mg RXC004 along with nivolumab. The results from the combination study are expected to read out in H2 2021 and will be used to define a dose of RXC004 to be used in combination with standard dose nivolumab in a Phase 2 study in patients with genetically selected microsatellite stable (MSS) metastatic colorectal cancer (MSS mCRC), which is planned to start to recruit patients in H2 2021.

Lisa Anson, Chief Executive Officer of Redx Pharma said: "We are delighted to have initiated dosing of our first patient cohort in our Phase 1 RXC004 and anti-PD1 combination study. We believe that RXC004 has the potential to offer clinical benefit both as a monotherapy and in combination with immunotherapies for patients with Wnt-driven advanced solid tumours.

This important milestone opens our combination study programme, which is an exciting addition to our ongoing Phase 1 monotherapy study which is on track to report headline results by mid 2021"

What is RXC004?
RXC004 is a potent, selective, oral small molecule inhibitor of the enzyme, porcupine, a key activator of Wnt ligands in the Wnt signalling pathway. Aberrant Wnt signalling contributes directly to tumour growth and plays an important role in immune evasion, which leads to resistance to immune checkpoint inhibitors such as nivolumab. By selecting patients with tumours that have high Wnt ligand dependency, such as tumours with mutations in the RNF43 gene and fusions in the RSPO gene family, RXC004 has an opportunity to both directly inhibit the tumour growth and have an immune-enhancing effect to attack the tumour.

Why are we testing anti-PD1 and RXC004 in combination?
Immune checkpoint inhibitors (ICIs) such as anti-PD-1 antibodies have revolutionised the treatment of cancer, but do not work in all patients. Wnt pathway activation can enhance the ability of the tumour to evade destruction by the immune system and could contribute to lack of response to ICIs in these tumours. Our scientists have demonstrated preclinically that RXC004 can block activation of the Wnt pathway and restore the ability of the immune system to fight the tumour. Thus, RXC004 offers potential as a monotherapy or combination therapy, which we are now testing in clinical trials.

RXC004 Clinical trials
RXC004 is currently being investigated in a Phase 1 study, with top line safety and tolerability data as a monotherapy expected by mid 2021, with more detailed data expected to be presented at a conference in H2 2021. Following completion of the monotherapy Phase 1, clinical proof-of concept monotherapy studies in genetically-selected patients with metastatic colorectal cancer, genetically selected pancreatic cancer and all comers biliary cancer are expected to initiate. These studies are in addition to the combination study programme

On April 28, 2021 CorMedix Inc. (Nasdaq: CRMD), a biopharmaceutical company focused on developing and commercializing therapeutic products for the prevention and treatment of infectious and inflammatory disease, reported that CorMedix management will participate in investor meetings at the 7th Annual Truist Securities Life Sciences Summit taking place on May 4 – 5, 2021 (Press release, CorMedix, APR 28, 2021, View Source [SID1234578867]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

On April 28, 2021 Olatec Therapeutics LLC (Olatec) reported the first publication from its preclinical studies with dapansutrile in selected cancer models (Press release, Olatec Therapeutics, APR 28, 2021, View Source [SID1234578829]). The data in this paper, entitled "Targeting tumor-derived NLRP3 reduces melanoma progression by limiting MDSCs expansion", is published in the Proceedings of the National Academy of Sciences (PNAS). Under leading investigators, including Charles Dinarello MD, Olatec’s CSO, and Mayumi Fujita MD PhD, the data show that blocking NLRP3 with oral dapansutrile resulted in a significant reduction in tumor growth and progression when compared to untreated mice with induced melanoma.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Cutaneous melanoma is an aggressive malignancy of the skin with a high mortality rate. In melanoma patients, elevated levels of myeloid-derived suppressor cells (MDSCs) are known to correlate with stage, metastasis and poor outcomes in comparison to patients with low levels of these cells. This is due to the fact that MDSCs activation suppresses the immune response to tumor cells, ultimately leading to melanoma expansion and progression. Activation and amplification of MDSCs are largely due to the production of IL‑1β by melanoma cells.

At present, one of the most common treatments for melanoma is immunotherapy, e.g., anti-PD-1 therapy, which stimulates the immune system to kill tumor cells. Despite the significant benefit to and improved prognosis of patients with advanced melanoma treated with anti-PD-1 therapy, a significant proportion of patients fail to respond due to resistance to this treatment.

"Despite breakthrough immunotherapies over the last ten years, melanoma remains a clinical challenge because tumor cells escape from destruction due to upregulated IL‑1β," said Dr. Fujita. "Our studies using a melanoma model in mice show that by reducing IL‑1β with dapansutrile, the immune system returns to its active state with restoration of its antitumor functions. As a result, melanoma tumor growth was reduced in mice. Our data further demonstrate that dapansutrile in combination with immunotherapy restores the host’s antitumor response and results in a greater reduction in the melanoma tumor than either treatment alone."

Dr. Dinarello added, "Targeting NLRP3 with dapansutrile to inhibit IL‑1β represents a new strategy for treating melanoma and other inflammatory tumors, especially to augment response rates to anti-PD-1 antibodies and to overcome resistance to other immunotherapies."

Underscoring the relevance of these ground-breaking preclinical studies, Damaris Skouras, co-Founder and CEO, said, "Based upon the positive data from our preclinical studies in melanoma, Olatec is positioned for a clinical trial to study dapansutrile in combination with a PD-1 inhibitor with the objective of inhibiting melanoma-associated IL‑1β inflammation in order to mitigate immunotherapy resistance and prevent tumor progression."

About Melanoma

In the United States, melanoma has been estimated to be the fifth most common type of new cancer diagnosis in both men and women and the most common cause of skin cancer-related death. Furthermore, among young adults, it is the second most common invasive cancer, and according to the American Academy of Dermatology Association, 1 in every 5 people in the United States suffers from skin cancer. The incidence of melanoma is increasing worldwide with reports estimating the global melanoma therapeutics market to reach over $12 billion by 2025.

About Dapansutrile

Dapansutrile (lab code: OLT1177) is an investigational small molecule, new chemical entity that specifically binds to and blocks NLRP3 (nucleotide-binding and oligomerization domain [NOD‑, leucine rich repeat-, pyrin domain-containing 3), the sensor molecule integral in the formation of the NLRP3 inflammasome. Inflammasomes are multiprotein complexes involved in intracellular surveillance of danger signals that trigger an intense inflammatory response, via generation of bioactive IL-1β and IL-18 through caspase-1 activation. Dapansutrile has been shown to prevent the formation of the NLRP3 inflammasome, which in turn inhibits the production of IL‑1β and IL‑18. NLRP3 is one of the most characterized inflammasome sensors due to its involvement in a wide range of disorders, including sterile inflammation, infections and rare genetic autoimmune syndromes. Dapansutrile is in Phase 2 clinical development and has been well tolerated and shown to improve clinical outcomes in patients with acute gout flare (see The Lancet Rheumatology) and heart failure (see Journal of Cardiovascular Pharmacology). Dapansutrile has also been observed to have antiinflammatory properties and other promising activity in a broad spectrum of over 20 preclinical animal models including arthritis, asthma, acute myocardial infarction, contact dermatitis, multiple sclerosis, melanoma and breast cancers, spinal cord injury and Alzheimer’s disease.