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 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 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 Cureteq AG (Cureteq), a clinical stage company developing innovative medicines with the support of a sophisticated artificial intelligence (AI) platform, reported the company has in-licensed its first compound, and will develop it as a potential first-in-class treatment for multiple cancers, initially for brain and kidney cancer (Press release, Oncoteq, MAY 30, 2022, View Source [SID1234651596]). The development path is guided by AI and builds on strong preclinical and clinical data.

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The compound, M8891, is a small-molecule methionine aminopeptidase 2 (MetAP2) inhibitor licensed from global science and technology company Merck based in Darmstadt, Germany. This is the first of what is planned to be a series of acquisitions by Cureteq as the company looks to build a pipeline of novel and better potential medicines against a range of diseases. Cureteq sets out to pioneer a new standard for AI-supported drug development to the benefit of patients, doctors and society.

Cureteq leverages AI to identify the top potential indications of a given molecule and to devise optimized and de-risked clinical development plans. Such an approach provides for accelerated development of new medicines to treat the diseases for which they will be most effective and have the highest chance of becoming available to patients. The AI-platform differentiates from other AI approaches by its breadth and depth, connecting billions of data points according to the most relevant medical concept; this greatly enhances the quality and impact.

Mads Dalsgaard, Chief Executive Officer of Cureteq AG, commented:
"We are very excited to complete our first in-licensing deal and commence development, combining the AI-technology and our medical expertise. M8891 has the potential to be a first-inclass treatment for cancers, such as kidney and brain cancers, which both have a devastating impact on patients’ lives. We are pleased to collaborate with Merck by carrying forward this promising molecule and excited about proving the power of AI in drug development".

M8891, through a unique mechanism of action (MetAP2 inhibition), inhibits both the cancer cells and their ability to generate new blood vessels in vitro, which is necessary for tumor growth. It is thought that this can potentially suppress the progression of the malignant disease, shrink, or even eliminate the cancer, especially if M8891 is combined with other anti-tumor treatments. Preventing disease progression or shrinking the tumor with safe and tolerable drugs is usually associated with an improved quality of life and helps patients to minimize fatal complications from their disease or may even prolong an otherwise drastically shortened life expectancy.

In a recent phase 1, dose-escalation study in patients with solid tumors, M8891 as monotherapy was demonstrated to have acceptable safety and also showed preliminary signs of anti-tumor efficacy. Such data add to the robust preclinical data package supporting potential anti-tumor activity across a broad range of tumors. Cureteq plans to validate the AI generated hypotheses preclinically and in a multi-cohort, Phase 1b study of M8891 in combination with current standardof-care treatments for kidney and brain cancer; patient enrollment is expected to commence in 2023.

M8891 will be developed by Oncoteq AG, a newly established subsidiary of Cureteq.

On May 30, 2022 The board of directors of HBM Holdings Limited reported that the Company has commenced collaborations on antibody-drug conjugate ("ADC") projects with LegoChem Biosciences Inc. ("LegoChem Biosciences" or "LCB") and Duality Biotherapeutics ("Duality Biologics") as part of the Company’s ADC development and collaboration strategy (Press release, Harbour BioMed, MAY 30, 2022, View Source [SID1234628154]).

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In 2022, the Company entered into a collaboration agreement with Duality Biologics, pursuant to which the Company shall grant the exclusive rights of its monoclonal antibodies for specific tumor to Duality Biologics to develop the world’s first-in-class ADCs based on Duality Biologics’ Duality Immune Toxin Antibody Conjugate platform.

The Company also entered into a license agreement with LegoChem Biosciences in 2022, over an antibody for ADC. The agreement also contemplated that the contracting parties may collaborate in developing the ADC for therapeutic applications.

Pursuant to the license agreements and subject to the terms and conditions thereof, the Company shall receive upfront payments, milestone payments and sales-based royalties. The Company believes that the aforementioned collaborations will contribute further to the Harbour Mice platform’s ADC Ecosphere with the Company’s other industrial leading partners such as MediLink Therapeutics and Kelun-Biotech.