On April 12, 2023 The Center for iPS Cell Research and Application, Kyoto University (Director: Dr. Jun Takahashi; "CiRA") and Astellas Pharma Inc. (TSE: 4503, President and CEO: Naoki Okamura, "Astellas") reported to have entered into the second phase of a joint research agreement to further promote the utilization of differentiated cells and tissues derived from human induced pluripotent stem cells (iPS cells)*1 and to create innovative medical solutions (Press release, Astellas, APR 12, 2023, View Source [SID1234629985]).

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During the first phase (July 2017 to March 2023), the two parties conducted comprehensive joint research on drug discovery applications of iPS cells. In the second phase, the two parties will build on their past efforts and incorporate digital technology into a technological platform for differentiated cells and tissues derived from iPS cells to further accelerate drug discovery and develop the technology to cover an even broader range of medical applications.

1. Establishment of a technological platform for stable and high-quality production of iPS cell-derived differentiated cells and tissues by utilizing Mahol-A-Ba

Maintaining iPS cells in an appropriate state and programming them to differentiate into target cells require the technical expertise and astute judgment of experienced researchers. In addition, to evaluate the pharmacological effects of a compound, expert researchers must confirm whether iPS cells have differentiated correctly into target cells to completion. Therefore, the two parties will establish a technological platform for the stable and high-quality production of differentiated cells and tissues derived from iPS cells.

For the purpose of this joint research, CiRA installed Astellas’ cellular drug discovery platform "Mahol-A-Ba"*2. The two parties will work together to construct digital protocols for Mahol-A-Ba to develop a high-quality and highly reproducible differentiation induction method and create a library of differentiated cells.

2. Construction of a new evaluation system using iPS cell-derived differentiated cells and tissues

Cell types of various tissues and organs differentiated from iPS cells have been utilized to investigate the causes of diseases and to evaluate the pharmacological properties of drug candidates. By constructing advanced pathological models and models that can evaluate individual patient differences, the two parties aim to improve clinical predictability further and create medical solutions to treat diseases for which conventional methods have failed to provide viable options.

3. Creation of cell therapy programs using iPS cell-derived differentiated cells

The two parties will apply 1. and 2. above to create new cell therapy programs and resolve issues faced by current cell therapy in general (e.g., the establishment of efficient differentiation methods to target cells).

"The joint research agreement with Astellas, which includes state-of-the-art core technology for drug discovery, will be of critical importance to generating new possibilities of drug discovery using iPS cell technology. I would like to express my sincere gratitude to Astellas," said CiRA Director Jun Takahashi. "Through this joint research, we hope to contribute to drug discovery and development of treatments for various diseases as soon as possible."

"We are pleased to enter into this joint research agreement," said Yoshitsugu Shitaka, Ph.D., Chief Scientific Officer at Astellas. "We hope that the collaboration between CiRA, who has expertise in iPS cells and cell therapy, and Astellas, who has proven capabilities in drug discovery, will deliver even greater VALUE to patients."

CiRA and Astellas will further promote the use of iPS cell-derived differentiated cells and tissues to create innovative medical solutions to offer new treatment options for patients, thereby contributing to the treatment of diseases with high unmet medical needs.

On April 12, 2023 Alligator Bioscience (Nasdaq Stockholm: ATORX) reported the completion of patient enrolment in the ongoing OPTIMIZE-1 Phase 2 trial of the company’s lead asset mitazalimab in 1st line metastatic pancreatic cancer (Press release, Alligator Bioscience, APR 12, 2023, View Source [SID1234629984]). Thanks to this acceleration in patient enrolment, Alligator confirms it expects to report top-line data in the beginning of Q1 2024.

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The open-label, multi-center study is assessing the safety and efficacy of mitazalimab (CD40 mAb) in combination with chemotherapy, mFOLFIRINOX, in previously untreated patients with metastatic pancreatic ductal adenocarcinoma.

"The completion of enrolment in OPTIMIZE-1 marks another important milestone in our clinical development of mitazalimab, which has been demonstrating outstanding potential in pancreatic cancer when combined with chemotherapy," said Søren Bregenholt, CEO of Alligator Bioscience. "Patient enrolment has been completed earlier than initially anticipated thanks to the diligent work of the Alligator organisation, thus significantly de-risking the program. The strong interim data released earlier this year showing an objective response rate (ORR) in excess of 50%, coupled with the high unmet medical need of patients with metastatic pancreatic cancer, has spurred significant interest in mitazalimab in the medical community and with potential partners. We are confident in the potential of mitazalimab as first-line treatment and looking forward to key survival data due later this year, and ultimately to the top-line readout expected at the beginning of next year."

In January 2023, Alligator announced strong interim results from OPTIMIZE-1, in which mitazalimab combined with mFOLFIRINOX demonstrated an ORR of 52% in 23 evaluable patients, as per the Response Evaluation Criteria in Solid Tumors (RECIST 1.1). In comparison, a similar patient population treated only with FOLFIRINOX reported an ORR of around 32%[1]. Mitazalimab in combination with mFOLFIRINOX also reported an interim disease control rate, the proportion of patients with objective response or stabilization of disease, of over 90%.

Alligator is planning to initiate discussions with regulators in the US and Europe on the best possible development and approval pathway for mitazalimab in pancreatic cancer later this year. Interim data from OPTIMIZE-1 on Progression Free Survival[2] and survival are due in mid-2023 and top-line data are expected in Q1 2024.

On April 12, 2023 Akoya Biosciences, Inc. (Nasdaq: AKYA) ("Akoya"), The Spatial Biology Company, reported the launch of PhenoCode Discovery Panels, which simplify spatial biology workflows performed on the company’s PhenoCycler-Fusion platform, at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting being held in Orlando, Florida, April 14-19, 2023 (Press release, Akoya Biosciences, APR 12, 2023, View Source [SID1234629983]).

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PhenoCode Discovery Panels are designed to advance cancer research by enabling thorough interrogation of tumors and the surrounding tumor microenvironment. Each of the ready-to-use, modular panels include biomarkers that can answer key biological questions related to immune profiling, lymphocyte profiling, tissue architecture, and immune activation and proliferation. The panels can be used on their own or combined to explore increasingly complex questions and significantly scale the "plex" of discovery in a stepwise fashion. Upfront assay development and validation time is significantly reduced, accelerating spatial discovery by 3x compared to standard workflows.

"The PhenoCode Discovery Panels further streamline and simplify the workflow on the PhenoCycler-Fusion System, offering new avenues of exploration for existing customers and paving the way for researchers who want to leverage this powerful technology for the first time," said Brian McKelligon, CEO of Akoya. "These panels are an important part of the spatial biology ecosystem which Akoya has established and continues to expand. Our vision is to offer a comprehensive suite of panels for multiple applications. We expect to launch additional PhenoCode Discovery Panels for protein biomarkers throughout 2023 and 2024, and introduce panels for RNA in the second half of this year."

The PhenoCode Discovery Panels will be highlighted at booth #1713 at AACR (Free AACR Whitepaper). More than a dozen posters describing use of the company’s spatial biology solutions will be shared at AACR (Free AACR Whitepaper) by Akoya scientists and collaborators.

Akoya scientists and collaborators will also share spatial biology case studies on the use of high plex spatial phenotyping to reveal new insights into tumor progression and treatment response in a spotlight session at AACR (Free AACR Whitepaper). Details of the presentation are as follows:

Date/Time: Monday, April 17, 2023, 10:00 AM
Location: Spotlight Theater C
Speakers:

Rajkumar Savai, PhD, Professor of Lung Microenvironmental Niche in Cancerogenesis, Max-Planck-Institute for Heart and Lung Research and Institute for Lung Health (ILH)
Jasmine Plummer, PhD Founding Director, Center for Spatial Omics, St. Jude Children’s Research Hospital
Oliver Braubach, PhD, Director of Applications, Akoya Biosciences
More details about Akoya’s AACR (Free AACR Whitepaper) activities and poster presentations can be found here.

On April 12, 2023 HUTCHMED (China) Limited ("HUTCHMED") (Nasdaq/AIM: HCM, HKEX: 13) reported that new and updated clinical and non-clinical data related to five HUTCHMED investigational drug candidates will be presented during the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2023 (AACR 2023), which will take place from April 14 to 19, 2023 in Orlando, Florida (Press release, Hutchison China MediTech, APR 12, 2023, View Source [SID1234629942]).

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Savolitinib

Title: A multicenter Phase II study of savolitinib in patients with MET-amplified gastroesophageal junction adenocarcinomas or gastric cancer
Lead Author: Lin Shen, MD, Peking University Cancer Hospital & Institute
Type: Poster presentation
Session Number: PO.CT02.01 – Phase II Clinical Trials 1
Abstract Link: View Source!/10828/presentation/10376

Title: Baseline and on-treatment plasma-based genomics as a predictor of outcome in SAVANNAH: Savolitinib + osimertinib in EGFRm MET overexpressed/​amplified NSCLC post-osimertinib
Lead Author: Ryan J Hartmaier, Ph.D, AstraZeneca
Type: Poster presentation
Session Number: LB294/7
Abstract Link: View Source!/10828/presentation/9996

Mesenchymal epithelial transition factor ("MET") gene amplification is associated with poor prognosis in gastric cancer ("GC") and gastroesophageal junction adenocarcinomas ("GEJ"). Savolitinib is a potent and highly selective oral MET tyrosine-kinase inhibitor.

Here we reported the preliminary efficacy and safety data from a Phase II trial of savolitinib monotherapy in patients with MET-amplified advanced or metastatic GC/GEJ (NCT04923932). Additionally, utility of plasma-based genomics was investigated in the SAVANNAH Phase II trial of savolitinib in addition to osimertinib in epidermal growth factor receptor (EGFR) mutated, MET overexpressed/amplified non-small cell lung cancer ("NSCLC") post osimertinib. First presentation of the SAVANNAH results occurred at the International Association for the Study of Lung Cancer (IASLC) 2022 World Conference on Lung Cancer (WCLC) in August 2022.

Surufatinib

Title: Surufatinib plus toripalimab for first-line treatment of advanced non-small cell lung cancer (NSCLC) with PD-L1 positive expression: A multicenter, single-arm phase 2 study
Lead Author: Ying Cheng, MD, Jilin Cancer Hospital
Type: Poster presentation
Session Number: PO.CT02.02 – Phase II Clinical Trials 2
Abstract Link: View Source!/10828/presentation/10405

Surufatinib (a small-molecule inhibitor of vascular endothelial growth factor receptor ("VEGFR") 1-3, fibroblast growth factor receptor ("FGFR") 1 and colony-stimulating factor 1 receptor ("CSF-1R")) plus toripalimab (an anti-programmed cell death protein-1 ("PD-1") antibody) showed encouraging antitumor activity in solid tumors. Programmed death ligand 1 ("PD-L1") expression is the established biomarker for first-line immune checkpoint inhibitors therapy in advanced NSCLC. We conducted an open-label, multi-cohort, single-arm Phase II study to evaluate the safety and efficacy of surufatinib plus toripalimab in patients with advanced solid tumors. Here, we reported the results of advanced NSCLC with PD-L1 positive expression cohort (NCT04169672).

HMPL-760

Title: HMPL-760 is a highly potent and selective reversible BTK inhibitor, targeting BTK and BTKC481S in B-cell malignancies
Lead Author: Linfang Wang, HUTCHMED
Type: Poster presentation
Session Number: PO.ET09.07 – Tyrosine Kinase and Phosphatase Inhibitors 1
Abstract Link: View Source!/10828/presentation/6728

Bruton’s tyrosine kinase ("BTK"), a member of the Tec family, plays a crucial role in signaling through B-cell receptor ("BCR"). BTK inhibition blocks BCR signals and prevents B-cell activation and growth. First-generation BTK inhibitors such as ibrutinib covalently binds to a cysteine residue ("C481") of BTK. Their most frequent acquired resistance is the development of a serine mutation in the binding site ("C481S"). Next generation BTK inhibitors such as HMPL-760 aim to overcome this resistance to first-generation inhibitors.

The poster outlined preclinical data showing HMPL-760 is a reversible, selective, highly potent BTK inhibitor targeting both BTKWT and BTKC481S. The first-in-human Phase I clinical trials of HMPL-760 are under way in patients with relapsed/refractory B-Cell Non-Hodgkin’s Lymphoma (NCT05190068).

HMPL-306

Title: Preclinical characteristic of HMPL-306, a CNS-penetrable dual inhibitor of mutant IDH1 and IDH2
Lead Author: Na Yang, HUTCHMED
Type: Poster presentation
Session Number: PO.ET01.01 – Oncogenes and Tumor Suppressor Genes as Targets for Therapy 1
Abstract Link: View Source!/10828/presentation/8579

Mutations in isocitrate dehydrogenase ("IDH") 1/2 are frequently identified in various cancers, such as acute myeloid leukemia ("AML"), cholangiocarcinoma, chondrosarcoma and glioma. Mutant IDHs ("mIDHs") cause accumulated 2-hydroxyglutarate, leading to blockage of cell differentiation, thereby inducing malignant transformation. Rare cases were identified carrying co-existing mutations in IDH1 and IDH2. mIDH isoform switching, from mutant IDH1 to mutant IDH2 and vice versa, have been reported as a mechanism of acquired resistance to IDH inhibition in AML and cholangiocarcinoma. Thus, simultaneous inhibition on both mIDH1 and mIDH2 may be a promising strategy to overcome resistance and improve clinical efficacy. HMPL-306, a dual inhibitor of mIDH1/mIDH2, developed by HUTCHMED, is being evaluated in clinical trials ().

The poster outlines preclinical data that shows that HMPL-306 is a potent, durable, dual inhibitor of IDH1/2 mutation that crosses the blood brain barrier and demonstrated effect on pharmacodynamic markers that lead to the differentiation of immature malignant cells to mature normal cells. The strong activity and favorable pharmacokinetics profiles support further clinical evaluation.

HMPL-453

Title: HMPL-453, a highly selective inhibitor of fibroblast growth factor receptors 1, 2, and 3, displays potent activity in FGFR-altered tumor models
Lead Author: Jia Hu, HUTCHMED
Type: Poster presentation
Session Number: PO.ET01.07 – Growth Factor Receptors as Therapeutic Targets
Abstract Link: View Source!/10828/presentation/8706

Fibroblast growth factors ("FGFs") and their receptors ("FGFRs") regulate numerous cellular processes. Dysregulation of FGFR signaling due to receptor fusion, mutation or amplification is observed across multiple cancer types, making activated FGFRs an important therapeutic target. Herein, we presented the preclinical characterization of HMPL-453, a highly potent and selective inhibitor of FGFR1, 2, and 3, discovered and being currently developed in Phase II clinical trial (NCT04353375) by HUTCHMED.

The presentation outlines preclinical data that shows that HMPL-453 is a highly potent and selective inhibitor of FGFR 1, 2, and 3 with strong activity against FGFR-deregulated tumors in preclinical models, supporting continued investigation in patients with FGFR alterations (such as fusion and mutation) either as a single agent or in combination with PD-1 blockade.

About Savolitinib (ORPATHYS in China)
Savolitinib is an oral, potent and highly selective MET tyrosine kinase inhibitor that has demonstrated clinical activity in advanced solid tumors. Іt blocks atypical activation of the MET receptor tyrosine kinase pathway that occurs because of mutations (such as exon 14 skipping alterations or other point mutations), gene amplification or protein overexpression.

Іn 2011, AstraZeneca and HUTCHMED entered a global licensing and collaboration agreement to jointly develop and commercialize savolitinib. Joint development of savolitinib in China is led by HUTCHMED, while AstraZeneca leads development outside of China. HUTCHMED is responsible for the marketing authorization, manufacturing and supply of savolitinib in China. AstraZeneca is responsible for the commercialization of savolitinib in China and worldwide. Sales of savolitinib are recognized by AstraZeneca.

About Surufatinib (SULANDA in China)
Surufatinib is a novel, oral angio-immuno kinase inhibitor that selectively inhibits the tyrosine kinase activity associated with VEGFR and FGFR, which both inhibit angiogenesis, and CSF-1R, which regulates tumor-associated macrophages, promoting the body’s immune response against tumor cells. Its unique dual mechanism of action may be very suitable for possible combinations with other immunotherapies, where there may be synergistic anti-tumor effects.

HUTCHMED currently retains all rights to surufatinib worldwide.

About HMPL-760
HMPL-760 is an investigational, non-covalent, third-generation BTK inhibitor. It is a highly potent, selective, and reversible inhibitor against both wild-type and C481S-mutated BTK.

HUTCHMED currently retains all rights to HMPL-760 worldwide.

About HMPL-306
HMPL-306 is a novel dual-inhibitor of ꞮDH1 and ꞮDH2 enzymes. ꞮDH1 and ꞮDH2 mutations have been implicated as drivers of certain hematological malignancies, gliomas and solid tumors, particularly among acute myeloid leukemia patients.

HUTCHMED currently retains all rights to HMPL-306 worldwide.

About HMPL-453
HMPL‑453 is a novel, highly selective and potent inhibitor targeting FGFR 1, 2 and 3. Aberrant FGFR signaling has been found to be a driving force in tumor growth (through tissue growth and repair), promotion of angiogenesis and resistance to anti-tumor therapies. Abnormal FGFR gene alterations are believed to be the drivers of tumor cell proliferation in several solid tumor settings.

HUTCHMED currently retains all rights to HMPL-453 worldwide.

On April 11, 2023, NovAccess Global Inc. ("NovAccess" or the "company") entered into a securities purchase agreement (the "SPA") with 1800 Diagonal Lending LLC ("1800 Diagonal Lending") and issued a convertible promissory note in the original principal amount of $79,250 (the "note") to 1800 Diagonal Lending pursuant to the SPA (Filing, 8-K, NovAccess Global, APR 11, 2023, View Source [SID1234630251]). The loan funded on April 14, 2023. NovAccess will use the proceeds of the loan for general working capital purposes.

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NovAccess provided typical representations and agreed to standard covenants pursuant to the SPA. The SPA does not include any financial covenants.

The note bears interest at 8% a year and is due on April 11, 2024. NovAccess may prepay the note upon payment of a prepayment penalty ranging from 15-25% of the amount outstanding on the note when prepaid. Under the terms of the note, NovAccess may not sell a significant portion of its assets without the approval of 1800 Diagonal Lending, must comply with the company’s reporting requirements under the Securities Exchange Act of 1934, and must maintain the listing of the company’s common stock on the OTCQB Market or other exchange. NovAccess’ failure to comply with any of these covenants, among other matters, would constitute an event of default. Upon an event of default, the note will bear interest at 22% and 1800 Diagonal Lending will be entitled to its costs of collection.

Beginning on October 8, 2023, 1800 Diagonal Lending may convert the amount outstanding under the note into shares of NovAccess common stock at a conversion price equal to 65% of the average of the three lowest trading prices of the stock during the fifteen trading days before the conversion date.

The SPA and note are filed as exhibits to this Current Report on Form 8-K. The descriptions above are qualified in their entirety by reference to the full text of these documents.