On May 30, 2022 Faron Pharmaceuticals Ltd (AIM: FARN, First North: FARON), a clinical stage biopharmaceutical company focused on building the future of immunotherapy by harnessing the power of the immune system to tackle cancer and inflammation, reported that new biomarker data from patients treated with bexmarilimab as part of the ongoing phase I/II MATINS (Macrophage Antibody to Inhibit Immune Suppression) trial, will be presented at the upcoming American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2022 Annual Meeting being held in Chicago, US from June 3 – 7 (Press release, Faron Pharmaceuticals, MAY 30, 2022, View Source [SID1234615233]). These data (Abstract #2645) will be featured in the "Developmental Therapeutics—Immunotherapy" session on Sunday, June 5, 2022 at 9:00 AM EDT.

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The MATINS trial is investigating the safety and efficacy of bexmarilimab as a monotherapy in patients with solid tumors who have exhausted all treatment options. Faron’s wholly-owned novel precision cancer immunotherapy targets Clever-1, a receptor known to be expressed on immunosuppressive macrophages in the tumor microenvironment. Bexmarilimab works by converting highly immunosuppressive M2 macrophages to immune stimulating M1 macrophages, which activates antigen presentation and promotes interferon gamma secretion by leukocytes. This can turn "cold" tumors into "hot" tumors; allowing the immune system to recognize and target cancer cells.

The biomarker analysis shows that the tumors of patients benefiting from bexmarilimab treatment expressed low levels of PD-L1 – a patient group that generally does not receive benefit from or is ineligible for treatment with currently approved checkpoint inhibitors. Median PD-L1 Combined Positive Score (CPS) was 1 (range 0-2) in patients that benefitted from bexmarilimab. The PD-L1 CPS score was 5 (range 0-100) for patients who did not benefit from bexmarilimab treatment. Further, the analysis showed that patients with higher levels of Clever-1 positive intra-tumoral cells were more likely to experience a clinical benefit when treated with bexmarilimab [15% vs 3%, respectively; p=0.038].

"While the arrival of currently available checkpoint inhibitors was, undoubtedly, one of the most exciting breakthroughs in cancer care, their low response rate in most tumor types continues to hinder their clinical application," said Petri Bono, MD, PhD., Chief Medical Officer, Terveystalo Finland and Principal Investigator of the MATINS trial. "There remains an urgent need for effective new treatment options, including novel assets that work synergistically with existing checkpoint inhibitors to ignite and amplify the patient’s immune response."

These data build on Faron’s continued research to identify the patient population most likely to benefit from bexmarilimab treatment and follow the Company’s earlier findings, announced in December 2021, that patients with low baseline serum levels of serum interferon gamma (IFNy) and tumor necrosis factor alpha (TNFa) were more likely to experience clinical benefit following treatment with bexmarilimab. Those patients with immunologically cold tumors also exhibited an ignition of immune response, as indicated by increased levels of IFNy following therapy, which suggests bexmarilimab may serve as a catalyst for the immune system allowing initially checkpoint inhibitor resistant or ineligible patients to become responsive to PD-1 blockade.

"Using a validated staining technique, these preliminary biomarker analyses indicate that bexmarilimab treatment may benefit patients whose tumors express low levels of PD-L1 and higher levels of CLEVER-1 positive intra-tumoral cells, which is opposite to what is usually seen with checkpoint inhibitors and other T cell activating agents," said Marie-Louise Fjällskog, M.D., Ph.D., Chief Medical Officer of Faron. "We are encouraged by this data as it furthers our belief that bexmarilimab has the potential to bring the promise of immunotherapy to a much broader patient population both as a monotherapy and in combination with currently approved anti-PD-1/L1 therapies."

About Bexmarilimab

Bexmarilimab is Faron’s wholly-owned, investigative precision immunotherapy with the potential to provide permanent immune stimulation for difficult-to-treat cancers through targeting myeloid cell function. A novel anti-Clever-1 humanised antibody, bexmarilimab targets Clever-1 positive (Common Lymphatic Endothelial and Vascular Endothelial Receptor 1) tumour associated macrophages (TAMs) in the tumour microenvironment, converting these highly immunosuppressive M2 macrophages to immune stimulating M1 macrophages. In mouse models, bexmarilimab has successfully blocked or silenced Clever-1, activating antigen presentation and promoting interferon gamma secretion by leukocytes. Additional pre-clinical studies have proven that Clever-1, encoded by the Stabilin-1 or STAB-1 gene, is a major source of T cell exhaustion and involved in cancer growth and spread. Observations from clinical studies to date indicate that Clever-1 has the capacity to control T cell activation directly, suggesting that the inactivation of Clever-1 as an immune suppressive molecule could be more broadly applicable and more important than previously thought. As an immuno-oncology therapy, bexmarilimab has potential as a single-agent therapy or in combination with other standard treatments including immune checkpoint molecules in both solid tumors and hematologic malignancies. Beyond immuno-oncology, it offers potential in infectious diseases, vaccine development and more.

About MATINS

The MATINS (Macrophage Antibody To INhibit immune Suppression) study is a first-in-human open label phase I/II clinical trial investigating the tolerability, safety and efficacy of bexmarilimab in ten different hard-to-treat metastatic or inoperable solid tumour cohorts – cholangiocarcinoma, colorectal cancer, cutaneous melanoma, ER+ breast cancer, gastric cancer, hepatocellular carcinoma, ovarian cancer, uveal melanoma, pancreatic cancer and anaplastic thyroid carcinoma – which are all known to host a significant number of Clever-1 positive tumour-associated macrophages (TAMs). The completed Part I of the trial dealt with tolerability, safety and dose escalation. The ongoing Part II is focused on identifying patients who show an increased number of Clever-1 positive TAMs and exploring safety and efficacy. Part III will be focused on assessing efficacy. Data from MATINS have shown that bexmarilimab has the potential to be the first macrophage immune checkpoint therapy. To date, the investigational therapy has been shown to be safe and well-tolerated, making it a low-risk candidate for combination with existing cancer therapies, and has demonstrated early signs of clinical benefit in patients who have exhausted all other treatment options.

On May 30, 2022 Sirnaomics Ltd. (the "Company" or "Sirnaomics", stock code: 2257.HK), a leading biopharmaceutical company in discovery and development of RNAi therapeutics, reported the launch of a Phase I clinical trial of the Company’s siRNA (small interfering RNA) drug candidate, STP705, in adults undergoing abdominoplasty for submental fat reduction (Press release, Sirnaomics, MAY 30, 2022, View Source [SID1234615232]). This study is the first application for Sirnaomics to apply an RNAi therapeutic candidate for medical cosmetology treatment.

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The global non-invasive fat reduction market size was valued at USD1.1 billion in 2021 and is anticipated to register a compound annual growth rate (CAGR) of 16.1% from 2022 to 2030, up to approximately USD4.0 billion (Grand View Research). Non-invasive fat reduction is a procedure that is done to decrease or eliminate stubborn fat pockets in specific areas of the body by using methods like cryolipolysis, radio frequency, and laser lipolysis. Non-invasive devices that are used in these procedures to permanently abolish fat cells are approved by the U.S. Food and Drug Administration (FDA) as their efficiency and safety have been tested and the results have been proven to show significant results. However, the market is currently dominated by devices that have mild therapeutic effects and require multiple treatment sessions. Sirnaomics will initially focus on the use of STP705 for submental fat reduction.

The dose-ranging, randomized, double-blind, vehicle-controlled study will enroll 10 patients to evaluate the safety and tolerability of STP705, which will be delivered via subcutaneous injection. The primary endpoints are to assess injection comfort, characterize local and systemic safety, and evaluate histological changes of subcutaneous doses of STP705, and to compare the safety and tolerability of three different concentrations of STP705 to select dosages for future studies.

"Submental fullness is a common condition that is resistant to diet and exercise and is influenced by multiple factors including aging and genetics," said Sirnaomics Executive Director and Chief Medical Officer Michael Molyneaux M.D. "Our goal in expanding our applications of STP705 with this study is to examine the safety and efficacy of this treatment in patients who are undergoing abdominoplasty. We hope to use the information from this study to expand into the treatment of submental fat reduction and other areas of non-invasive fat sculpting. This Phase I study will serve as a blueprint for future studies of STP705 in the medical aesthetics category."

"The current devices and procedures for non-invasive fat reduction have mild therapeutic effects, and require multiple and sometimes challenging treatment sessions, which are costly for patients and don’t always achieve the desired results," said Dr. Patrick Lu, Founder, Chairman of the Board, Executive Director, President and CEO of Sirnaomics. "Based on a discovery from our previous clinical study and a series of preclinical evaluations with animal models, we decided to expand STP705 therapeutic application into medical aesthetics with this Phase I study."

About STP705

Sirnaomics’ leading product candidate, STP705, is a siRNA (small interfering RNA) therapeutic that takes advantage of a dual-targeted inhibitory property and polypeptide nanoparticle (PNP)-enhanced delivery to directly knock down both TGF-β1 and COX2 gene expression. The product candidate has received multiple IND approvals from both the U.S. Food and Drug Administration (FDA) and the Chinese National Medical Products Administration (NMPA), including treatments of cholangiocarcinoma, non-melanoma skin cancer and hypertrophic scar. STP705 has also received Orphan Drug Designation for treatment of cholangiocarcinoma (CCA) and primary sclerosing cholangitis (PSC). STP705 is currently in five clinical trials for different indications: a Phase IIa for squamous cell carcinoma in situ (isSCC), a Phase II for basal cell carcinoma (BCC), a Phase I/II for keloid scarring, a Phase I/II for hypertrophic scar (HTS), and a Phase I for liver cancer (basket).

On May 30, 2022 Antengene Corporation Limited ("Antengene" SEHK: 6996.HK), a leading innovative, commercial-stage global biopharmaceutical company dedicated to discovering, developing and commercializing first-in-class and/or best-in-class therapeutics in hematology and oncology, reported that the first patient has been dosed in the Phase I STAMINA-001 trial to evaluate ATG-037 as a monotherapy or in combination with pembrolizumab in patients with locally advanced or metastatic solid tumors in Australia (Press release, Antengene, MAY 30, 2022, View Source [SID1234615231]).

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The primary objective of the study is to evaluate the safety, tolerability, recommended Phase II dose and preliminary antitumor efficacy of ATG-037 as a monotherapy and in combination with pembrolizumab. Secondary objectives include characterization of the pharmacology of ATG-037.

ATG-037 is an orally available, small molecule CD73 inhibitor. CD73 is an "immune checkpoint mediator"[1] that interferes with anti-tumor immune responses by generating adenosine, which leads to immunosuppression in the tumor microenvironment. ATG-037 can reverse adenosine-mediated immunosuppression[2]. It has demonstrated promising preclinical efficacy as a monotherapy and in combination with ICIs and chemotherapy agents. In preclinical studies, this compound overcomes the "hook effect" that is common in anti-CD73 antibodies. In addition, GLP toxicology studies indicate the compound has a potentially wide therapeutic window.

"While ICIs are widely used in the treatment of various cancers, many patients have resistant or refractory disease, which has created a large unmet need," said Dr. Ganessan Kichenadasse, principal investigator, Southern Oncology Clinical Research Unit in Adelaide, Australia. "Mounting evidence suggests that adenosine plays a critical role in suppressing anti-tumor immunoactivity. CD73 can convert adenosine monophosphate (AMP) to adenosine. ATG-037, an orally available, small molecule CD73 inhibitor, can block the generation of adenosine. We are excited to be a part of the STAMINA-001 Trial. This Phase I study brings together a group of highly experienced Australian investigators to collaborate with Antengene. We are excited to assess the therapeutic potential of ATG-037 for patients with solid tumors as a single agent as well the exploring the opportunity for benefit with the addition of an ICIs."

"Developing agents that can act in the tumor microenvironment to reverse immunosuppression is one of the key focus areas for Antengene, " said Dr. Kevin Lynch, Antengene’s Chief Medical Officer. "Preclinical data presented at the 2022 American Association of Cancer Research Annual Meeting (AACR 2022) showed that ATG-037 had a stronger ability to restore T-cell function in higher-AMP environments compared with anti-CD73 monoclonal antibodies. These data highlighted the potential therapeutic advantages of small molecule inhibitors of CD73 over blocking antibodies, either as a monotherapy, or in combination with other immune-oncological treatments. We have been very pleased with the drug’s performance in preclinical studies and are hopeful that in this Phase I study ATG-037 can demonstrate the tolerability and signals of activity that will allow us to move forward into a broader development program. We are very excited about the start of this first in human clinical trial and look forward to next steps with ATG-037."

About the STAMINA-001 Trial

The STAMINA-001 trial is a Phase I multi-center, open-label, dose finding study of ATG-037 monotherapy or combination therapy with pembrolizumab in patients with locally advanced and metastatic solid tumors. Subjects will begin with two monotherapy cycles and then be allowed to receive the addition of pembrolizumab. The primary objective of the study is to evaluate the safety and tolerability of ATG-037 and to determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) and/or optimal biological dose of ATG-037 monotherapy and preliminary efficacy. Secondary objectives include characterization of the pharmacology of ATG-037. As a Phase I study, there will be intensive safety monitoring throughout the trial.

About ATG-037

ATG-037 is an orally-available, highly selective small molecule that completely blocks the activity of CD73. CD73, an ecto-5′-nucleotidase, catalyzes the conversion of adenosine monophosphate (AMP) to adenosine. Adenosine production leads to significant immunosuppression in the tumor microenvironment, now recognized as one of the most important immunomodulatory pathways in the tumor microenvironment.

Many human tumors overexpress CD73 and this expression is frequently associated with poor prognosis. Blocking CD73 has been shown to be effective in controlling tumor growth and metastases and CD73 inhibitors may increase the therapeutic activity of ICIs and chemotherapy agents. Clinical data so far indicate that CD73 inhibitors add little additional toxicity to standard of care treatments.

On May 30, 2022 Endeavor BioMedicines, a clinical-stage biotechnology company targeting the core drivers of terminal diseases including oncology and fibrosis, and xCures, a company that aims to improve cancer outcomes and accelerate cancer research using artificial intelligence, reported a partnership that gives patients enrolling in Endeavor’s clinical trials access to the xCures platform to find the best available treatment options suited to their individual tumor profile (Press release, xCures, MAY 30, 2022, View Source [SID1234615229]). The partnership helps identify patients whose cancers harbor the PTCH1 mutation and may be eligible for Endeavor’s clinical trial. The xCures platform also enables patients to find more suitable treatment options if they are ineligible.

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"Endeavor’s partnership with xCures aligns with our patient-first focus and will help guide any patients with cancer who contact us to find the best treatment options for them," said Anita DiFrancesco, Vice President of Clinical Operations at Endeavor BioMedicines. "We recently dosed the first patient in a Phase 2 study evaluating ENV-101 (taladegib), a small molecule inhibitor of the Hedgehog signaling pathway, in patients with advanced solid tumors harboring PTCH1 loss of function mutations. Endeavor and xCures will work together to identify PTCH1 mutations while also providing alternative treatment options for patients who are ineligible for our trials."

Patients will be registered on the xINFORM platform. Once a patient is registered, xCures will review their cancer history. For patients without molecular profiling, xCures will assist patients with tumor sequencing. After the genomic information is added to a patient’s profile, they will receive a report that lists the best treatment options based on their cancer history and their genomic profile. If the patient has the PTCH1 mutation, they and their physician will be made aware of the option to enroll in the Endeavor clinical trial. Patients whose tumors are negative for the PTCH1 mutation will receive a personalized list of treatment options that they should discuss with their oncologist.

"xCures is pleased to partner with Endeavor to help improve outcomes for cancer patients by helping them understand their treatment options and support them and their physician with access," said Bryan Federowicz, Vice President of Clinical Operations at xCures. "This partnership is an example of how collaboration between industry, doctors and patients can provide the best, uniquely tailored medicine for each individual patient."

ENV-101: Targeting the Hedgehog Signaling Pathway in Oncology and Fibrosis

ENV-101 (taladegib), an orally available small molecule inhibitor of the Hedgehog signaling pathway, has already demonstrated preliminary clinical efficacy and safety in nearly 200 subjects enrolled across six completed studies. Initially targeted for a broad group of patients with basal cell carcinoma (BCC), Endeavor is now investigating precision therapy approaches for ENV-101 in multiple types of cancers driven by oncogenic driver mutations in PTCH1, as well as in idiopathic pulmonary fibrosis (IPF).

PTCH1 oncogenic driver mutations in the Hedgehog signaling pathway are found in approximately 2% of all cancers. Because of its prevalence across multiple types of cancer, Endeavor plans to enroll patients in a tumor agnostic study that includes any patient with oncogenic hedgehog mutations irrespective of tissue of origin. Endeavor is currently enrolling patients in an open label Phase 2 clinical trial in oncology (www.clinicaltrials.gov identifier NCT05199584).

On May 30, 2022 NNL reported that have made a breakthrough for producing Lead-212, a very important medical radioisotope for treating cancer, but which is difficult to produce and therefore in short supply (Press release, National Nuclear Laboratory, MAY 30, 2022, View Source [SID1234615228]).

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Used in an emerging medical treatment known as Targeted Alpha Therapy (TAT), Lead-212 labelled targeting molecules destroy cancer cells while minimising damage to healthy parts of the body. TATs have gained traction because they fight cancer while limiting the side effects experienced by patients. Yet the supply of Lead-212, like other key medical radioisotopes, faces a global shortage which constrains their use, with no production route in existence in the UK.

The production process for the UK’s first home-grown supply of Lead-212 has been developed at NNL’s Preston Laboratory. It is currently going through quality assurance and scale-up work. To achieve this, NNL is working closely with clinicians and academics including at Queen Mary University of London and King’s College London and their associated nuclear medicine departments at St Bartholomew’s Hospital and Guy’s and St Thomas’ NHS Foundation Trust.

Dr Jane Sosabowski is Reader in Molecular Imaging at Queen Mary’s Barts Cancer Institute and researcher at City of London Cancer Research UK-RadNET, one of a network of centres of excellence and state-of-the-art facilities working to tackle the major challenges of radiobiology and radiation oncology. She said:

"This new initiative is immensely exciting, offering a huge boost to the future of molecular radiotherapy treatment and personalised medicine in the UK. Barts Cancer Institute and Radionuclides for Health UK welcomes the leadership that NNL is showing on this issue. It is an important step in re-establishing UK supply of medical radioisotopes and securing the future of research in this important sphere of human health."

Dr Paul Howarth, Chief Executive Officer for NNL, said:

"Fifty years ago, the UK led the world in medical radioisotope research and production, yet today we rely on imports often from ageing facilities. Establishing a sovereign home-grown supply of these important medical radioisotopes would be transformative for healthcare in the UK and, given the global nature of the supply challenge, citizens of the other countries we supply.

"There is great demand from the healthcare profession for the UK to develop an indigenous supply of medical radioisotopes and this work is core to NNL’s purpose of nuclear science to benefit society."

Nick Hanigan, NNL’s Health and Nuclear Medicine Director, said:

"The production process we have developed, which requires complex chemical separation and purification of nuclear material, builds on NNL’s world-leading capability in this area. Lead-212 limits the side effects of cancer treatment because it is delivered directly to cancerous cells. Our plan now is to scale the production route in order to remove the significant supply constraints currently faced by hospitals.

"This breakthrough development is a single aspect of our work on medical radioisotopes, a tool used on a daily basis by every hospital in the UK to diagnose and treat health conditions including many types of cancer, heart disease and thyroid disease and for the early detection and assessment of brain disorders such as epilepsy, Alzheimer’s disease and other forms of dementia."