On May 4, 2023 XNK Therapeutics AB ("XNK") reported that the company’s autologous natural killer (NK) cell therapy candidate XNK04 will be evaluated in combination with an ADCC competent PD-L1 inhibitor in liver cancer under a research agreement with a global pharma company (Press release, XNK Therapeutics, MAY 4, 2023, View Source [SID1234631070]).

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The preclinical validation study aims to test the cell therapy candidate XNK04 alone and in combination with an antibody checkpoint inhibitor against autologous cancer cells isolated from patients with hepatocellular carcinoma (HCC). The study will provide data to support initiation of a potential future clinical phase I/II trial.

"We will explore synergistic effects of the combination. This is a study where we test an individualized NK cell-based therapy on isolated patient-specific tumor material, and it is our ambition to validate this combination approach in HCC," said Johan Liwing, CEO at XNK.

The study will test the hypothesis that the well documented big pharma PD-L1 antibody, when combined with the expanded and activated NK cells, will facilitate NK cell-mediated cytotoxicity against HCC tumor cells.

"We are excited about entering into this collaborative study. This preclinical research agreement with a renowned big pharma company lends valuable support to our clinical strategy and shows that there is strong interest in the industry for our technology," said Markus Thor, Chief Business Officer at XNK.

The HCC study adds to XNK’s clinical phase II program in multiple myeloma and preclinical programs in urothelial cancer and acute myeloid leukemia (AML). XNK retains all commercial rights to XNK04.

About Hepatocellular Cancer

Cancer in the liver is a major health problem and is the fourth leading cause of cancer-related death worldwide. Each year more than 800,000 people are diagnosed with liver cancer worldwide. HCC constitutes around 80% of all primary liver cancers. Risk factors for developing HCC include e.g. fatty liver disease, alcohol consumption and hepatitis B and C. Treatments include surgery, trans-arterial chemoembolization (TACE), chemotherapy, targeted drug therapy and checkpoint inhibitors. The medical need remains significant with high recurrence rates and with 5-year survival rates around 20%.

On May 4, 2023 Sapience Therapeutics, Inc., a clinical-stage biotechnology company focused on the discovery and development of peptide therapeutics to address oncogenic and immune dysregulation that drive cancer, reported that it was awarded a $2 million, two-year Small Business Innovation Research (SBIR) grant from the National Cancer Institute (NCI) of the National Institutes of Health (NIH) (Press release, Sapience Therapeutics, MAY 4, 2023, View Source;catenin-antagonist-301816245.html [SID1234631069]). The proposed non-clinical studies will investigate pharmacodynamic biomarkers for ST316, a first-in-class β-catenin antagonist, and evaluate the impact of ST316 on the tumor microenvironment (TME) in patient-derived cancer models.

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"This award provides further validation of our novel approach with ST316 to impact the Wnt/β-catenin signaling pathway, a known oncogenic driver of many cancers and a key regulator of the tumor microenvironment," said Jim Rotolo, Ph.D., SVP, Translational Pharmacology and Head of Research of Sapience Therapeutics. "ST316 has tremendous therapeutic promise, with a robust preclinical data package that includes a favorable safety profile and significant anti-tumor activity. We look forward to building upon these data with this grant award and evaluating ST316 in patients in our upcoming Phase 1-2 clinical study."

ST316 is a first-in-class peptide antagonist of the interaction between β-catenin and its co-activator BCL9, a complex that drives oncogenesis in multiple cancers where aberrant Wnt/β-catenin pathway signaling is observed. In March 2023, Sapience announced that it received clearance from the U.S. Food and Drug Administration (FDA) to proceed with a Phase 1-2 clinical trial of ST316 for the treatment of solid tumors. In addition, at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2023, Sapience presented late-breaking data on ST316 highlighting its immunotherapeutic potential.

The award will utilize patient-derived xenograft (PDX) models to investigate pharmacodynamic (PD) biomarkers and evaluate the impact of ST316 on the TME, namely macrophage polarization, tumor infiltrating lymphocyte (TIL) expression in tumors and the impact in combination with a PD-1 inhibitor. This grant was supported by the National Cancer Institute of the National Institutes of Health under Award Number 2R44CA265503-02A1. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

About ST316

ST316, a first-in-class β-catenin antagonist, is in Phase 1 clinical development following the clearance of its Investigational New Drug (IND) application by the U.S. Food and Drug Administration in March 2023. β-catenin is a critical member of the canonical Wnt signaling pathway, a well-known development stage pathway that has been considered an "undruggable" cancer target, as small molecules have proven ineffective or toxic. Disruption of the interaction between BCL9 and β-catenin with ST316 reduces oncogenic Wnt-signaling, suppressing transcription of Wnt target genes resulting in tumor cell death and a pro-inflammatory tumor microenvironment, without disruption of homeostatic Wnt function.

In the second quarter of 2023, the Phase 1 dose-escalation portion of the Phase 1-2 study will begin enrolling patients with selected advanced solid tumors likely to harbor abnormalities of the Wnt/β-catenin signaling pathway. The Phase 2 dose-expansion portion aims to continue to assess the safety of ST316 as well as proof of concept in four specific tumor types known to harbor abnormalities of the Wnt/β-catenin signaling pathway.

On May 4, 2023 CRB091, a novel drug candidate developed by Cancer Research and Biotechnology AG (CRB), reported to have shown significant promise in reducing cancer cell proliferation in difficult-to-treat cancers such as colorectal and triple-negative breast cancers (Press release, Cancer Research and Biotechnology, MAY 4, 2023, View Source [SID1234631068]). The preclinical studies conducted by an independent research laboratory in the UK demonstrated a significant reduction in human cancer cell proliferation in vitro, with a synergistic effect between the product’s single ingredients.

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TNBC is the most aggressive type of breast cancer in women with a 5-years survival rate of 66% and a very low survival rate of 12% after metastasis. Conventional cancer treatments often come with severe side effects, limiting their use and efficacy. Furthermore, targeted therapies and new immunological treatments suit only a limited patient population, while drug resistance can develop rapidly. CRB091 offers a well-tolerable and effective therapy that could address the shortfalls of existing treatments.

CRB091’s active molecules have been proven safe for human use, and CRB anticipates initiating the first-in-human clinical trials in the US in 12 months. The FDA’s Pre-Investigational New Drug (Pre-IND) application advice is scheduled in Q3 2023, with the IND filing in Q3 2024.

As a preclinical oncology company, CRB is focused on developing drugs that address the metabolic disease that induces carcinogenesis. By providing a particularly effective and well-tolerated therapy, CRB091 has the potential to significantly improve the treatment of triple-negative breast cancer and other difficult-to-treat cancers.

With the meaningful efficacy demonstrated on human cancer cell lines, the Switzerland-based startup is poised to take a significant step towards human use of the novel treatment.

On May 4, 2023 Citius Pharmaceuticals Inc. (Nasdaq: CTXR) ("Citius" or the "Company"), a late-stage biopharmaceutical company dedicated to the development and commercialization of first-in-class critical care products, reported that it has entered into definitive agreements with certain healthcare-focused and institutional investors for the purchase of an aggregate of 12,500,001 shares of its common stock and accompanying warrants to purchase up to an aggregate of 12,500,001 shares of its common stock, at a purchase price of $1.20 per share and accompanying warrant in a registered direct offering (Press release, Citius Pharmaceuticals, MAY 4, 2023, View Source [SID1234631067]). The closing of the offering is expected to occur on or about May 8, 2023, subject to the satisfaction of customary closing conditions.

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H.C. Wainwright & Co. is acting as the exclusive placement agent for the offering.

The warrants have an exercise price of $1.50 per share, will be exercisable six months from the date of issuance, and will expire five years from the date of issuance.

The aggregate gross proceeds to the Company from the offering are expected to be approximately $15 million, before deducting the placement agent fees and other offering expenses payable by the Company. Citius currently intends to use the net proceeds from the offering for general corporate purposes, including pre-clinical and clinical development of our product candidates and working capital and capital expenditures.

The securities described above are being offered pursuant to a "shelf" registration statement (File No. 333-255005) filed with the Securities and Exchange Commission (SEC) and declared effective on April 16, 2021. The offering is being made only by means of a prospectus, including a prospectus supplement, forming a part of the effective registration statement. A final prospectus supplement and the accompanying prospectus relating to the securities being offered will be filed with the SEC and be available at the SEC’s website at www.sec.gov. Electronic copies of the final prospectus supplement and the accompanying prospectus relating to the securities being offered may also be obtained, when available, by contacting H.C. Wainwright & Co., LLC at 430 Park Avenue, 3rd Floor, New York, NY 10022, by calling (646) 975-6996 or emailing [email protected].

This press release shall not constitute an offer to sell or the solicitation of an offer to buy any of the securities described herein, nor shall there be any sale of these securities in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to the registration or qualification under the securities laws of any such state or jurisdiction.

On May 4, 2023 ABM Therapeutics, an innovative clinical-stage biopharmaceutical company, with an emphasis on developing drugs with high blood–brain barrier (BBB) penetration for CNS diseases including brain metastases, reported that the first patient was successfully dosed with ABM-168 in the United States (Press release, ABM Therapeutics, MAY 4, 2023, View Source [SID1234631066]).

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MEK (mitogen-activated protein kinase kinase), a key kinase of the MAPK pathway, is frequently activated in various cancers, including those with RAS mutations. These mutations are present in 20% of human cancers and 20-30% of NSCLC. ABM-168, a novel small molecule MEK inhibitor developed by ABM, exhibits good water solubility, high cell permeability and brain penetration. Preclinical studies have clearly demonstrated its anti-cancer properties, particularly in intracranial animal models.

"The dosing of the first patient with ABM-168 in the USA represents another important milestone for ABM. ABM-168 is a strategically important program for ABM’s development of combination therapies," Dr. Chen Chen, founder and CEO of ABM Therapeutics said. "Selective MEK inhibitors have the ability to inhibit tumor growth and induce cell death in RAF- and RAS-mutant cell lines. A MEK inhibitor in combination with a BRAF inhibitor has been demonstrated to be more effective and less toxic than a single BRAF inhibitor, which has become the standard of care for patients with BRAF-mutated melanoma. The combination of a MEK inhibitor with other anti-cancer drugs such as KRAS inhibitors and PD-1/PD-L1 antibodies is also explored. We look forward to the early clinical data which will help us to figure out the most effective combination for treating cancers, particularly those with high brain metastasis rates."

This phase I clinical trial in the US is a first-in-human multicenter, open-label, dose escalation and cohort expansion study, which is intended to assess the safety, tolerability, and pharmacokinetics of ABM-168 monotherapy in adult patients with advanced/metastatic solid tumors.

"We are very pleased to reach our study’s first patient dosed milestone at NEXT Oncology – Dallas, one of the clinical trial centers for this novel MEK inhibitor and collaborate with all study sites and investigators," said Dr. Zane Yang, CMO of ABM, "ABM will strive for ABM-168 clinical development to fulfill unmet medical needs and offer more therapeutic options. This makes a major step for our mission, passionate about developing drugs and improving patients’ quality of life."

As a clinical-stage biotechnology company, ABM Therapeutics has built a broad pipeline to construct a robust proprietary Brain-Penetrant Kinase Drug Discovery Platform (BPKddTM). Its first drug candidate ABM-1310, the next generation of BRAF inhibitor, is under clinical studies in both the US and China and has shown good safety profile including tolerability. ABM Therapeutics is in the process of Series B+ round financing, and looks forward to cooperating with international pharmaceutical companies, domestic and foreign biopharmaceutical companies, and securities and funds.

About ABM-168

ABM-168 is a novel small molecule MEK inhibitor with high water solubility, cell and brain permeability. It has demonstrated anti-cancer efficacy in vitro in multiple cancer cell lines and in vivo in multiple xenograft animal models. It was granted clearance of the Investigational New Drug (IND) application to proceed with the first-in-human clinical trial in October 2022 by the US FDA. More information about ABM’s ongoing ABM-168 trial is available at View Source (NCT 05831995) and on the company website at www.abmtx.com.