On October 17, 2023 BeiGene, Ltd. (NASDAQ: BGNE; HKEX: 06160; SSE: 688235), a global biotechnology company, reported that the Phase 3 RATIONALE 315 study met its dual primary endpoints of major pathological response (MPR) by Blinded Independent Pathology Review (BIPR) and event-free survival (EFS) by Blinded Independent Central Review (BICR), demonstrating statistically significant and clinically meaningful improvements in patients with resectable Stage II or IIIA NSCLC treated with tislelizumab in combination with chemotherapy before surgery and as a single agent after surgery versus neoadjuvant chemotherapy plus placebo followed by placebo after surgery (Press release, BeiGene, OCT 17, 2023, View Source [SID1234636054]). The tislelizumab plus chemotherapy regimen also showed a statistically significant improvement in pathological complete response (pCR), the key secondary endpoint, after neoadjuvant therapy versus chemotherapy. The MPR and pCR data will be featured as a late-breaking mini oral presentation on October 23 at 2:55 p.m. CEST at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2023 (Abstract #LBA58).

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In the study, 56.2% of NSCLC patients treated with tislelizumab in combination with chemotherapy before surgery achieved MPR, compared to 15.0% of patients treated with chemotherapy alone (difference: 41.1%; 95% CI: 33.2-49.1, p<0.0001). MPR is defined as less than 10% residual viable tumor after neoadjuvant therapy. Additionally, 40.7% of patients on the tislelizumab-based regimen achieved pCR, defined as no viable residual tumor after neoadjuvant therapy, compared to 5.7% of patients treated with chemotherapy alone (difference: 35.0%; 95% CI: 27.9-42.1, p<0.0001). Tislelizumab plus chemotherapy was generally well tolerated, with no new safety signals identified.

Additionally, at a recent prespecified interim analysis conducted by the independent data monitoring committee (IDMC), the tislelizumab-based regimen demonstrated a statistically significant improvement in EFS per assessment by BICR. Detailed results will be submitted for presentation at an upcoming medical conference.

"Lung cancer remains the most common type of cancer and the leading cause of cancer-related death worldwide. Despite available treatment options, rates of recurrence within five years remain unacceptably high, underscoring the need for innovative new neoadjuvant and adjuvant interventions to help improve patient outcomes," said Mark Lanasa, M.D., Ph.D., Chief Medical Officer, Solid Tumors at BeiGene. "The data from RATIONALE 315 are encouraging and demonstrate that early integration of tislelizumab into the treatment paradigm may help both improve responses at the time of surgery and reduce the recurrence risk for these patients. These results add to the growing evidence suggesting the potential benefits of tislelizumab in treating patients with NSCLC."

About RATIONALE 315 (NCT04379635)

RATIONALE 315 is a randomized, double-blind, placebo-controlled, Phase 3 trial evaluating the efficacy and safety of neoadjuvant tislelizumab plus platinum-based doublet chemotherapy, followed by surgery and subsequent adjuvant tislelizumab, compared to placebo plus neoadjuvant platinum-based doublet chemotherapy followed by surgery and subsequent adjuvant placebo in patients with resectable Stage II or IIIA NSCLC. The primary endpoints are MPR rate by BIPR and EFS by BICR. The key secondary endpoint is pCR. Other secondary endpoints included overall survival (OS), objective response rate (ORR), disease-free survival (DFS) as assessed by BICR, and investigator assessed EFS. A total of 453 patients were enrolled and randomized 1:1 to receive either tislelizumab or placebo in combination with chemotherapy.

About Tislelizumab

Tislelizumab is a humanized IgG4 anti-PD-1 monoclonal antibody, with high affinity and binding specificity against PD-1, specifically designed to minimize binding to Fc-gamma (Fcγ) receptors on macrophages, helping to aid the body’s immune cells to detect and fight tumors. In pre-clinical studies, binding to Fcγ receptors on macrophages has been shown to compromise the anti-tumor activity of PD-1 antibodies through activation of antibody-dependent macrophage-mediated killing of T effector cells.i,ii,iii,iv

The tislelizumab development program encompasses 21 registration-enabling clinical trials in more than 30 countries and regions. To date, BeiGene has announced positive readouts from 10 Phase 3 pivotal studies across multiple tumor types and disease settings, such as NSCLC, small cell lung cancer, gastric cancer, ESCC, hepatocellular cancer, and nasopharyngeal cancer. More information on the clinical trial program for tislelizumab can be found at: View Source

Tislelizumab is currently under review by the U.S. Food and Drug Administration (FDA) and received approval by the European Commission for advanced or metastatic ESCC after prior chemotherapy. Additionally, the FDA recently accepted for review a Biologics License Application for tislelizumab as a first-line treatment for patients with unresectable, recurrent, locally advanced, or metastatic ESCC. The European Medicines Agency (EMA) is reviewing a marketing authorization application for tislelizumab as a treatment for locally advanced or metastatic non-small cell lung cancer (NSCLC) after prior chemotherapy, and in combination with chemotherapy for previously untreated locally advanced or metastatic NSCLC.

Regulatory submissions for tislelizumab are also under review by authorities in Australia, Brazil, China, Korea, Israel, New Zealand, Singapore, Switzerland, and the U.K. Tislelizumab is approved for 11 indications in China and is the leading PD-1 inhibitor in the country.

On October 17, 2023 Akoya Biosciences, Inc. (Nasdaq: AKYA) ("Akoya"), The Spatial Biology Company, reported that researchers from Akoya Biosciences and The University of Queensland’s Frazer Institute have comprehensively mapped the spatial proteome of head and neck squamous cell carcinoma (HNSCC) using ultrahigh-plex spatial phenotyping (Press release, Akoya Biosciences, OCT 17, 2023, View Source [SID1234636053]). Spatial phenotyping consists of whole-slide imaging of tissue sections at single-cell resolution to visualize and quantitate biomarker expression and reveal how cells interact and organize across the entire tissue landscape.

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The study, published in GEN Biotechnology in an article titled "Mapping the Spatial Proteome of Head and Neck Tumors: Key Immune Mediators and Metabolic Determinants in the Tumor Microenvironment" identified a high degree of intra- and inter-tumoral heterogeneity intrinsic to head and neck cancers and advances the understanding of the mechanistic basis of variable clinical responses.

The study analyzed head and neck cancer tissues from a patient with varying responses to immune checkpoint inhibitor (ICI) therapy. The analysis was conducted using a panel of 100+ biomarkers to measure key cancer hallmarks of tumor and immune biology with Akoya’s PhenoCycler-Fusion system. The PhenoCycler-Fusion is the fastest spatial biology solution available which enables rapid imaging of whole slides at single-cell resolution.

"This study represents a significant advancement in multiplexed imaging and, to our knowledge, is the first single-cell spatial proteomic dataset integrating information from immune, metabolic and stress pathways to provide a holistic view into the biology of heterogenous HNSCC tumors" noted Niyati Jhaveri, PhD, Head of Applications at Akoya Biosciences. "It provides an analytical framework for future spatial studies leveraging the resolution, plex and speed of Akoya’s solution to decipher the complex nuances of human tissues in homeostasis and disease."

A pivotal discovery in the study highlighted the divergent enrichment of functionally specialized immune cell subsets, as well as distinct metabolic and stress signatures organized within specific spatial domains in the tumor. This overarching observation in the paper underscored the existence of heterogeneous niches and competitive microenvironments, potentially serving as defining factors for clinical response and resistance.

"Immune checkpoint inhibitors have shown promising results in recurrent and metastatic cases of HNSCC," said Dr. Arutha Kulasinghe, of The University of Queensland’s Frazer Institute, leader of the Clinical-oMx Lab, and one of the paper’s authors. "Durable treatment results, however, are observed in only 30% of patients, indicating that new biomarkers for stratification of responders and non-responders are needed. The dichotomy of immune activation-induced death and tumor progression we observed in an individual patient’s tissue sample correlated with the partial response seen with ICI therapy. We believe that the approach outlined in this study will pave the way towards a new understanding of tumor microenvironment features associated with response and sensitivity to immune checkpoint inhibitor therapies in head and neck cancer and other solid malignancies."

On October 17, 2023 AIM ImmunoTech Inc. (NYSE American: AIM) ("AIM") reported that it has entered into an agreement with Azenova, LLC ("Azenova"), a professional business development (BD) consulting firm, to support efforts to partner AIM’s pipeline programs with a particular focus on the company’s lead asset, Ampligen, for the treatment of various malignant solid tumors (Press release, AIM ImmunoTech, OCT 17, 2023, View Source [SID1234636052]).

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Azenova has been engaged to assist AIM with its BD efforts with the goal of entering into a partnership, out-license or other transaction whereby a biopharmaceutical company takes on the further development and commercialization of Ampligen with the goal of maximizing value to AIM. This process may not result in any transaction and the company does not intend to disclose additional details unless and until it has entered into a definitive agreement.

"With our growing body of compelling clinical data, we believe Ampligen has significant potential to provide a therapeutic solution for a wide range of cancers, immune disorders and viral diseases. We believe the timing of our engagement with Azenova perfectly aligns their BD expertise with our strategic vision to maximize the opportunities for our Ampligen pipeline programs and to unlock significant value in the asset," commented AIM Chief Executive Officer Thomas K. Equels.

Azenova provides a wide range of services to support clients in their partnership, licensing, and other transactional activities. This includes determining opportunities for partnership (assets and technologies), identification and assessment of potential partners and leading all steps involved in engaging partners and establishing definitive BD transaction agreements. Azenova’s principals, Jeff Southerton, PhD, MBA, and Stacy Evans, MD, MBA, have more than 50 years of combined BD experience in the biopharmaceutical industry leading transactions across a wide range of deal structures in multiple therapeutic areas, including significant experience in oncology.

"With AIM’s emerging data showing the promise of Ampligen as a therapeutic across a pipeline of malignant and often end-stage solid tumors, Azenova is excited to be formally engaged by AIM to assist the company with materializing a potential value inflecting BD transaction for the company," commented founder of Azenova, Jeff Southerton.

On October 16, 2023, ImmuneOnco Biopharmaceuticals (Shanghai) Co., Ltd. (referred to as "ImmuneOnco""the company’, Hong Kong Stock Exchange stock code: 01541.HK) reported that the company’s independently developed humanized IgG1 CD24 antibody(Project number: IMM47) was approved by the National Medical Products Administration (NMPA) for clinical trials (Press release, ImmuneOnco Biopharma, OCT 16, 2023, View Source [SID1234655694]). This is another milestone achievement in the rapid development of ImmuneOnco.

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IMM47 had also made a number of progresses previously by the efforts of the ImmuneOnco team. On September 27, the Australian phase I clinical trial of IMM47 successfully completed the enrollment of the first subject and officially entered the clinical research stage. The preclinical research results of the IMM47 project were published in "Antibody Therapeutics" on September 9. So far, IMM47 has obtained two authorized patents in China, and Japan, two pending patent applications in the United States and the European Union, and one pending patent application that may enter multiple approval of PCT patent of contracting countries in the future. In addition, we are ready to submit an IND application for IMM47 to the U.S. Food and Drug Administration (FDA) in near future.

CD24 is widely expressed in a variety of solid tumors including breast cancer, non-small cell lung cancer, colorectal cancer, hepatocellular carcinoma, renal cell carcinoma, ovarian cancer, and lymphoma, and is considered as an important marker of poor prognosis in these cancers which exhibits great clinical research potential.

With high specificity and high affinity to CD24 expressed on tumor cells, IMM47 can block immunosuppressive signals transmitted from the CD24/Siglec-10 pathway to macrophages, natural killer cells (NK) and T cells. By genetically engineered improved IgG1 Fc, IMM47 effectively activates macrophage and natural killer cell immune responses through powerful ADCP and ADCC. In preclinical animal in vivo efficacy studies, IMM47 showed to significantly increase the number of M1 macrophages in tumor tissues and downregulate CD24 expression in tumor cells, which also provide chances in combination with PD-1/PD-L1 immune checkpoint inhibitors and other drugs.

Dr. Tian, Wenzhi, founder and chairman of Immune Onco, said:" We are very pleased to see that our clinical trial application for IMM47, a humanized monoclonal antibody targeting CD24 for cancer treatment, was approved by the National Medical Products Administration (NMPA). The antibody screening for CD24 was quite challenging due to its small size of extracellular domain which exhibits weaker immunogenicity. We persevered through the accumulation of a lot of trivial work and finally got the IMM47 molecule with high affinity and specificity. With differentiated molecular design, IMM47 can specifically bind to CD24 and effectively activate macrophages and natural killer cell immune responses. Preclinical studies have shown that IMM47 has strong anti-tumor activity with great clinical development value. We will quickly advance the clinical trial of IMM47 to benefit more patients."

On October 16, 2023 SOTIO, a clinical-stage immuno-oncology company owned by PPF Group, reported a license and option agreement with Synaffix B.V., a Lonza company, to develop next-generation antibody-drug conjugates (ADCs) for the treatment of solid tumors (Press release, SOTIO, OCT 16, 2023, View Source [SID1234649863]). SOTIO will leverage Synaffix’s ADC technology platform to develop up to three novel ADCs targeting distinct tumor-associated antigens.

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"At SOTIO, we are building a broad pipeline of next-generation ADCs to address the challenges of solid tumors – and access to Synaffix’s ADC platform technologies will ensure we remain at the leading edge of this space," said Radek Spisek, M.D., Ph.D., chief executive officer of SOTIO. "This collaboration combining SOTIO’s deep expertise in solid tumor drug development with Synaffix’s clinical-stage platform technology will drive important new innovations for the benefit of patients."

The deal enables SOTIO to combine its proprietary antibodies with Synaffix’s ADC technology platform in order to deliver innovative new ADCs that can overcome the challenges of treating solid tumors. In addition to GlycoConnect and HydraSpace, the deal also includes Synaffix’s potent linker-payload platform including multiple different payloads.

"Synaffix’s ADC technology perfectly complements the technologies already in SOTIO’s ADC platform, including the iADC technology licensed from NBE-Therapeutics and the ConjuALL technology licensed from LegoChem," said Martin Steegmaier, chief scientific officer of SOTIO. "The addition of Synaffix’s capabilities will greatly expand our ability to select and tailor the most suitable ADC technology and payload for the needs of a particular target and particular solid tumor indication."

Under the terms of the agreement, Synaffix is eligible to receive upfront and potential milestone payments worth up to $740 million, plus single-digit royalties on net sales. SOTIO will be responsible for research, development, manufacturing and commercialization of the ADC products, while Synaffix will closely support SOTIO’s research activities and be responsible for the manufacturing of components that are specifically related to its proprietary GlycoConnect, HydraSpace, and linker-payload technologies.

Peter van de Sande, head of Synaffix, added, "The selection of our ADC technologies by a seasoned ADC player like SOTIO is a strong recognition of the potential of these technologies to maximize the therapeutic index of ADCs. We look forward to partnering with SOTIO, and believe that with their singular focus on cancer immunotherapies and robust clinical pipeline, this partnership can deliver innovative medicines for patients in areas of high unmet medical need."

SOTIO is advancing a pipeline of novel ADCs tailored to address the treatment needs of specific solid tumor types. SOT102, the company’s most advanced ADC program, is a CLDN18.2-targeting ADC in Phase 1/2 development for the treatment of gastric, pancreatic and other cancers that have very few targeted treatment options available. The company is progressing dose-finding studies in the trial’s monotherapy arm, with SOT102 as a later-stage treatment, and recently announced the initiation of the trial’s combination therapy arm in first-line treatment of gastric and pancreatic cancer patients. SOTIO additionally has two other ADC programs in preclinical development.