On November 7, 2022 Personalis, Inc. (Nasdaq: PSNL) reported that the company will share data resulting from expanded features of its NeXT Platform at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting, November 8-12 in Boston, with three abstracts that highlight advanced R&D applications of next-generation sequencing (NGS) in immuno-oncology (Press release, Personalis, NOV 7, 2022, View Source [SID1234623311]).

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"To understand the complex dynamics of cancer and ultimately better predict response to therapy, we need to advance the tools we’re using to characterize the tumor microenvironment. We continue to build upon the suite of technologies in our ImmunoID NeXT Platform to enable the high-resolution study of immuno-oncology targets in an array of contexts, including improved neoantigen prediction, immune-composition profiling, and composite biomarker signatures," said Sean Boyle, PhD, Executive Director of Bioinformatics Science at Personalis.

The company will present the following posters at SITC (Free SITC Whitepaper)2022, as well as with customers including the Parker Institute for Cancer Immunotherapy (Abstracts 559 and 587) and Geneos Therapeutics (Abstracts 691 and 692).

Title: A combination of antigen presentation and T-cell recognition features improves neoantigen immunogenicity predictions (Abstract 51)

Overview: Tumor neoantigen burden outperformed tumor mutational burden in prediction of patient response to checkpoint inhibitor immunotherapy by better capturing the biological mechanism underlying response. However, immune recognition of neoantigens by T-cells requires more than antigen presentation, which has been the focus of tumor neoantigen burden thus far. To address this need, we extend the existing SHERPA MHC-presentation framework to predict neoantigen immunogenicity. By combining antigen presentation and T-cell recognition features in a two-tiered model, we can better predict immunogenic neoantigens and make progress towards using neoantigens as biomarkers to assess checkpoint inhibitor efficacy.

Title: Sensitive prediction of immunotherapy response by integrating immune infiltration and neoantigen presentation score in late-stage melanoma (Abstract 119)

Overview: Single-modality biomarkers such as tumor mutational burden (TMB) often fail to reliably predict response to immune checkpoint blockade (ICB), likely due to incomplete characterization of the complex tumor-immune interactions that influence treatment efficacy. We previously developed the composite biomarker, neoantigen presentation score (NEOPS), which integrates neoantigen processing and presentation potency, and showed it outperformed TMB and other single-modality biomarkers in predicting ICB response in melanoma. Here, we combined NEOPS with the assessment of tumor immune infiltration and demonstrated more accurate patient stratification for ICB response.

Title: Transcriptome augmentation provides accurate and sensitive quantification of genes associated with the tumor microenvironment (Abstract 146)

Overview: While malignant cells dictate much of the tumor biology, there is evidence that the tumor microenvironment (TME) also plays a significant role in disease progression and response to therapy. The role of the immune cells is particularly relevant in immunotherapy, and multiple transcriptome-based biomarkers have shown utility in predicting the efficacy of immune checkpoint blockade. However, little is known about the benefits of enhancing the depth and uniformity of transcriptome sequencing coverage for quantifying the TME cell type composition. Using the ImmunoID NeXT Platform, which combines high-quality exome and transcriptome sequencing with advanced informatics to comprehensively characterize the tumor and TME from a single FFPE tumor sample, applying augmented transcriptome coverage to the assessment of TME benefited the identification of marker genes for cell type enrichment analysis without introducing bias.

On November 7, 2022 Fulgent Genetics, Inc. (NASDAQ: FLGT), a technology-based genetic testing company focused on transforming patient care in oncology, infectious and rare diseases, and reproductive health, reported that it has completed an acquisition of Fulgent Pharma Holdings, Inc. ("Fulgent Pharma"), an independent clinical-stage, therapeutics development company focused on the development of innovative cancer treatments (Press release, Fulgent Genetics, NOV 7, 2022, View Source [SID1234623310]). Under the terms of the agreement, Fulgent Genetics acquired Fulgent Pharma for a total purchase price of approximately $100 million, subject to adjustments, to be paid with a combination of cash on hand and shares of common stock of Fulgent Genetics.

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The combined company plans to offer a vertically integrated solution to combat cancer with the potential to unlock significant long-term upside for both the therapeutic and diagnostic businesses, while effectively managing risk. Fulgent Pharma and Fulgent Genetics were previously both owned by Fulgent Therapeutics until 2016, when the businesses were separated ahead of the Initial Public Offering of Fulgent Genetics. The companies have operated as separate entities since 2016, enabling each business to focus on and achieve core objectives across genetic testing and therapeutic drug development. Over the last year, Fulgent Genetics has established a meaningful presence in the large market for molecular diagnostics and oncologic testing, most notably with the recent acquisitions of CSI Laboratories and Inform Diagnostics, and the opening of a state-of-the-art oncologic testing facility in southern California. Fulgent Pharma has developed a novel nanoencapsulation and targeted therapy platform, which is designed to improve the therapeutic window and pharmacokinetic profile of new and existing cancer drugs. Based on current studies and pre-designated criteria, Fulgent Pharma believes its lead drug candidate, FID-007, has achieved proof-of-concept in preliminary human clinical trials for the treatment of various cancer types, including Head and Neck, Ampullary, Pancreatic, NSCLC, and Breast.

"This acquisition advances our mission to build a holistic platform to provide comprehensive solutions and services across the cancer care continuum, including early detection, diagnostics, and monitoring, as well as drug discovery and development," said Ming Hsieh, Chairman and CEO of Fulgent Genetics and co-founder of Fulgent Therapeutics. "With my commitment and our teams already in place, the combination of these two businesses diversifies our assets and will, we believe, provide sustainable future revenue and margin opportunity through a potentially lucrative target oncology market."

"In addition to FID-007, our proprietary nano-drug delivery platform has generated a deep pipeline of wholly owned drug candidates, focused on additional target cancer indications, including one for colon cancer and one NCE (new chemical entity) targeting the STING pathway. Both have been tested extensively in preclinical studies," said Ray Yin, PhD., President and Chief Scientific Officer of Fulgent Pharma and co-founder of Fulgent Therapeutics. "Through this acquisition, Fulgent Pharma will have access to commercial relationships across the oncology market as well as capital to fund research, development and, assuming the requisite regulatory approvals, commercialization as part of Fulgent Genetics."

Strategic Vision

Attractive Lead Therapeutic Candidate FID-007 and Nanoencapsulation Technology: Fulgent Pharma’s lead program, FID-007, is a proprietary nanoencapsulated formulation of paclitaxel developed to improve the overall solubility profile of paclitaxel. Data observed from studies conducted to date suggest that nanoencapsulation of paclitaxel may improve the biodistribution and bioavailability to target tissues. Such data also demonstrate a favorable profile and further support potential applications in a broad range of indications including Head and Neck, Ampullary, Pancreatic, Lung, Breast, and Ovarian cancers.
Expanded Market Opportunity: FID-007 is currently being developed for 2nd and 3rd line treatment of Head & Neck (H&N) cancer, a potential $2.2+ billion target market opportunity. The company sees further opportunities in large multi-billion markets including NSCLC, Pancreatic, Breast, and Ovarian cancers where currently available therapies are suboptimal.
Strategic and Operational Synergies: Potential long-term value creation driven by the combination of therapeutic candidates and diagnostics expertise, designed to offer a comprehensive oncology-focused solution that enables precision medicine through in-house or partnered therapeutics programs underpinned by genetic data insights. In addition, Fulgent Pharma’s talented scientific team brings unique expertise to the combined businesses and creates a differentiated advantage in the oncology market.
Enhanced Commercial Profile: Following completion of development and regulatory approval, the combined company is positioned to be a "one-stop shop" that spans the life sciences chain and reaches the expanded customer base of Fulgent Genetics through its growing sales organization.
Attractive Capital Allocation Plan: Fulgent Genetics’ strong balance sheet and cash flows from operations are expected to be able to support the advancement of Fulgent Pharma’s R&D pipeline. Fulgent Genetics’ track record of integrating acquisitions, strategic partnerships, and disciplined execution has been a key element in the company’s growth. This acquisition is designed to align with Fulgent Genetics’ strategy to drive long term shareholder value through organic and inorganic initiatives across the genomics and, assuming the requisite regulatory approvals, therapeutics market segments.
Advisors

A special committee comprised of independent members of Fulgent Genetics’ board of directors was established to review this transaction. In consultation with its independent financial and legal advisors, the special committee recommended the board of directors approve the Fulgent Pharma acquisition. The special committee was advised by First Principles Advisory Group and Cooley LLP. Fulgent Genetics was represented in the transaction by Mintz, Levin, Cohn, Ferris, Glovsky and Popeo, P.C.; and Procopio, Cory, Hargreaves & Savitch LLP acted as legal counsel to Fulgent Pharma.

Conference Call Information

Fulgent Genetics will discuss this transaction during its scheduled third quarter 2022 earnings conference call and webcast being held today at 4:30 PM ET (1:30 PM PT). The call and associated presentation may be accessed through a live audio webcast on the Investor Relations section of the company’s website, View Source An audio replay will be available at the same location.

On November 7, 2022 InnoCare Pharma (HKEX: 09969; SSE: 688428), a leading biopharmaceutical company focusing on the treatment of cancer and autoimmune diseases, reported that 10 studies on the BTK inhibitor orelabrutinib developed by InnoCare were selected at the 64th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting on December 10-13, 2022, which will be held online and offline in New Orleans, United States (Press release, InnoCare Pharma, NOV 7, 2022, View Source [SID1234623309]).

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Oral Presentation

Title: Orelabrutinib, Rituximab, and High-Dose Methotrexate (HD-MTX) in Newly Diagnosed Primary Central Nervous System Lymphoma (PCNSL): A Retrospective Analysis on Efficacy, Safety, and Biomarker

Abstract Number: 558

Session Name: 627. Aggressive Lymphomas: Clinical and Epidemiological: Real World Evidence for Management of CNS Lymphoma and Post CAR T-cell relapse for aggressive B-cell NHL

Presentation Time: 1:15 PM, Dec. 11, 2022 (Sunday)

First Author: Shihua Zhao

Corresponding Author: Wenrong Huang

Poster Presentation 1

Title: A Multicenter, Single-Arm, Prospective Phase Ⅱ Study of Orelabrutinib Combined with High-Dose Methotrexate and Rituximab Sequential Autologous Hematopoietic Stem Cell Transplantation in Newly-Diagnosed Primary Central Nervous System Lymphoma

Abstract Number: 1624

Session Name: 626. Aggressive Lymphomas: Prospective Therapeutic Trials: Poster I

Presentation Time: 5:30-7:30 PM, Dec. 10, 2022 (Saturday)

First Author: Ji Ma

Poster Presentation 2

Title: Efficacy and Safety of Lenalidomide, Anti-PD-1 Antibody Combined with Orelabrutinib or Rituximab in the Treatment of Patients with Relapsed/Refractory Diffuse Large B-Cell Lymphoma

Abstract Number: 1636

Session Name: 626. Aggressive Lymphomas: Prospective Therapeutic Trials: Poster I

Presentation Time: 5:30-7:30 PM, Dec. 10, 2022 (Saturday)

First Author: Yuqing Miao

Corresponding Author: Hao Xu

Poster Presentation 3

Title: Preliminary Result of Phase 1 Trial of Orelabrutinib in Combination with Rituximab, Methotrexate, and Dexamethasone in Patients with Newly Diagnosed Primary CNS Lymphoma Implementing Bayesian Design for Dose-Seeking

Abstract Number: 2951

Session Name: 626. Aggressive Lymphomas: Prospective Therapeutic Trials: Poster II

Presentation Time: 6:00-8:00 PM, Dec. 11, 2022 (Sunday)

First Author: Yan Yuan

Corresponding Author: Tong Chen

Poster Presentation 4

Title: Thiotepa, Orelabrutinib, and Methotrexate Combined with or without the Rituximab Regimens in the Treatment of Patients with Central Nervous System Lymphoma

Abstract Number: 4291

Session Name: 627. Aggressive Lymphomas: Clinical and Epidemiological: Poster Ⅲ

Presentation Time: 6:00-8:00 PM, Dec. 12, 2022 (Monday)

First Author: Ruolan Zeng

Corresponding Author: Hui Zhou

Poster Presentation 5

Title: Orelabrutinib in Combination with Rituximab and chemotherapy for Newly Diagnosed Aggressive B-Cell Lymphoma: A Multicenter, Single-Arm, Prospective Study

Abstract Number: 4295

Session Name: 627. Aggressive Lymphomas: Clinical and Epidemiological: Poster Ⅲ

Presentation Time: 6:00-8:00 PM, Dec. 12, 2022 (Monday)

First Author: Xiangxiang Zhou

Corresponding Author: Xin Wang

Online Abstract 1

Title: A Phase III, Randomized, Double-Blind, Placebo-Controlled, Multi-Center Study Evaluating the Efficacy and Safety of Orelabrutinib Plus R-CHOP Versus Placebo Plus R-CHOP in Treatment-Naive Patients with Mcd Subtype Diffuse Large B-Cell Lymphoma

Abstract Number: 5525

First Author: Weili Zhao

Corresponding Author: Pengpeng Xu

Online Abstract 2

Title: A Phase I/II Study of Orelabrutinib Combined with Anti-Programmed Cell Death Protein-1 Antibody and Fotemustine for Patients with Newly Diagnosed Primary Central Nervous System Lymphoma (PCNSL)

Abstract Number: 5508

First Author: Xudong Zhang

Corresponding Author: Mingzhi Zhang

Online Abstract 3

Title: Preliminary Outcomes of Orelabrutinib Plus RCHOP in Treatment-Naïve Patients with Double-Expression Diffuse Large B Cell Lymphoma

Abstract Number: 5521

First Author: Yang Yang

Corresponding Author: Zhen Cai

Online Abstract 4

Title: Orelabrutinib and Venetoclax Show Synergistic Lethality in Double-Hit Lymphoma By Interfering with the Crosstalk between the PI3K/AKT and p38/MAPK Signaling

Abstract Number: 5248

First Author: Mengya Zhong

Corresponding Author: Bing Xu

About Orelabrutinib

Orelabrutinib is a highly selective BTK inhibitor developed by InnoCare for the treatment of cancers and autoimmune diseases.

On Dec. 25 2020, orelabrutinib received conditional approval from the China National Medical Products Administration (NMPA) in two indications: the treatment of patients with relapsed/refractory chronic lymphocytic leukemia (CLL) /small lymphocytic lymphoma (SLL), and the treatment of patients with relapsed/refractory mantle cell lymphoma (MCL). At the end of 2021, orelabrutinib was included into National Reimbursement Drug list to benefit more lymphoma patients.

The supplemental New Drug Applications of orelabrutinib for the treatment of R/R WM and R/R Marginal Zone Lymphoma were accepted in China.

In addition to the approved indications, multi-center, multi-indication clinical trials are underway in the US and China with orelabrutinib as monotherapy or in combination therapies, such as first line treatment of MCD subtype of diffuse large B-cell lymphoma (DLBCL).

Orelabrutinib was granted as Breakthrough Therapy Designation for the treatment of r/r MCL by U.S. Food and Drug Administration (FDA).

In addition, orelabrutinib is also being evaluated in global phase II studies for the treatment of Multiple Sclerosis (MS), and clinical trials for the treatment of SLE, Primary Immune Thrombocytopenia (ITP) and Neuromyelitis Optica Spectrum Disorder (NMOSD) in China.

On November 7, 2022 PathAI, a leading provider of AI-powered pathology tools to advance precision medicine, reported that the organization’s recent research will be presented at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s 37th annual meeting (SITC) (Free SITC Whitepaper), which will be held in Boston, MA from November 8-12, 2022 (Press release, PathAI, NOV 7, 2022, View Source [SID1234623308]). PathAI will share five new posters, all developed in collaboration with biopharmaceutical partners, that highlight their new AI-model development to support advances in oncology research across several disease areas such as non-small cell lung cancer (NSCLC), cholangiocarcinoma, and urothelial carcinoma.

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Last year at SITC (Free SITC Whitepaper), PathAI presented data highlighting their machine learning (ML) model that was developed to identify and quantify CD8+ T cells in digitized whole slide images of melanoma patients. PathAI has since expanded upon that research and will share data demonstrating how their newly developed ML-based models quantify CD8+ lymphocytes and CD8 topology classifiers across seven cancer types: NSCLC, urothelial carcinoma, head and neck squamous cell carcinoma, gastric cancer, colorectal cancer, pancreatic cancer, and hepatocellular carcinoma.

"Concordance analysis of AI-powered CD8 quantification and automated CD8 topology with manual histopathological assessment across seven solid tumor types" shows that PathAI’s ML model-predicted CD8+ cell counts are highly correlated with pathologist-generated counts across these tumor types. This poster also highlights PathAI’s ability to characterize the topology of CD8 expression across the tumor to predict immune-inflamed, excluded and desert immunophenotypes in these seven cancer types. This work demonstrates the power of PathAI’s digital pathology models for automated quantitation of the CD8+ lymphocytes and immunophenotyping in clinical samples, confirming the potential for this approach in immuno-oncology.

"Our latest results support and further extend our research in immuno-oncology for multiple disease areas," said Dr. Mike Montalto, Chief Scientific Officer at PathAI. "This is another big step forward in innovating and improving pathology research, future drug development, and, ultimately, patient outcomes."

Additionally, PathAI has developed a new deep-learning-based method for the analysis of whole slide image multiplex immunofluorescence (mIF) data in NSCLC. As the importance of spatial relationships between cells increases in immuno-oncology, "Identification of clinically relevant spatial phenotypes in large-scale multiplex immunofluorescence data via unsupervised graph learning in non-small cell lung cancer" aims to show how a deep-learning approach to mIF analysis can capture spatial phenotypes in NSCLC. The graph neural network (GNN) approach used in this study revealed distinct spatial phenotypes that can describe the organization of distinct cell types, such as cancer and immune cells. The relative amounts of these phenotypes in a cancer specimen are related to the immunogenicity and antigenicity of the cancer, as well as patient outcome. This new approach has potential to identify patterns in the spatial relationship between cells in NSCLC tissue.

The full list of PathAI’s poster presentations highlighting their biomarker and tumor microenvironment research products is listed below. More information on each research abstract can be found here.

On November 7, 2022 Aleta Biotherapeutics (Aleta), a privately held immuno-oncology company with novel biologic CAR T engagers that work in synergy with cell therapies to improve outcomes for patients, reported that the U.K. Medicines and Healthcare products Regulatory Agency (MHRA) has granted an Innovation Passport under the Innovative Licensing and Access Pathway (ILAP) for Chimeric Antigen Receptor (CAR) T-cell therapy Engager candidate ALETA-001 for the treatment of patients suffering from the B-cell malignancies, non-Hodgkin lymphoma a (NHL) and Acute Lymphoblastic Leukemia (ALL), and who have failed to respond or have relapsed post-CD19 CAR T-cell therapy (Press release, Aleta Biotherapeutics, NOV 7, 2022, View Source [SID1234623307]). ALETA-001 is expected to enter clinical development in 2023 with Cancer Research UK’s Centre for Drug Development sponsoring and conducting a Phase 1/2a clinical trial.

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The Innovation Passport is the first step in the ILAP process, triggering the MHRA and its partner agencies, including The All Wales Therapeutics and Toxicology Centre (AWTTC), National Institute for Health and Care Excellence (NICE), and the Scottish Medicines Consortium (SMC), to chart a roadmap for regulatory and development milestones to enable faster patient access to medicines in the U.K. To receive an Innovation Passport, a medicine must address conditions that are life-threatening or seriously debilitating, and there must be an existing significant patient or public health need.

"This designation for our biologic CAR T-cell therapy engager ALETA-001 marks an important step in addressing the high unmet need for patients who relapse or progress following CD19-targeted CAR T-cell therapy for blood cancers, such as lymphoma and leukemia," stated Paul Rennert, Co-Founder, Acting Chief Executive Officer and Chief Scientific Officer, Aleta Biotherapeutics. "In collaboration with our partner Cancer Research UK, we are excited to move ALETA-001 forward to potentially transform the lives of patients living with blood cancers," continued Rennert.

Dr. Nigel Blackburn, Cancer Research UK’s Director of Drug Development, stated, "We are so pleased to receive this designation for ALETA-001, which reboots CAR T-cell therapy by bridging a patient’s circulating CD19-targeted CAR T-cells to cancer cells expressing CD20. While CAR T-cell therapy has revolutionized hard-to-treat blood cancer outcomes, a majority of patients will see their cancer return, and this is where the critical potential of ALETA-001 exists. ALETA-001 is a promising approach to address this significant treatment gap for patients who currently lack effective options."

In June 2021, Aleta Biotherapeutics and Cancer Research UK announced a collaboration in which Cancer Research UK’s Centre for Drug Development will fund, sponsor, and conduct the first-in-human Phase 1/2a clinical trial of ALETA-001, which will be led by Dr. Sridhar Chaganti’s Cellular and CAR T-cell therapies team at the Queen Elizabeth Hospital and University Hospitals Birmingham NHS Foundation Trust, Birmingham UK. In the Cancer Research UK-sponsored trial, patients with B-cell lymphoma/leukemia who have received CD19-targeted CAR-T cell therapy but did not achieve a complete response or who relapsed from a complete response will be enrolled. Aleta retains all rights to further develop and commercialize ALETA-001.

About Biologic CAR T-Cell Therapy Engager (CTE) ALETA-001

ALETA-001 is an off-the-shelf preclinical biologic program developed to treat and prevent cell therapy relapse of existing CD19-targeted CAR T-cell therapies, termed CAR19 T cells. ALETA-001 bridges CAR19 T cells to a second antigen, CD20. ALETA-001 binds to B-cell lymphomas and leukemias expressing CD20 antigens and restores tumor expression to CD19. ‘Recoating’ CD20-expressing cancer cells to express CD19 addresses the critical issues of tumor CD19 antigen loss and density and holds the potential to restore potent killing in patients who are no longer responding to previously administered, circulating CD19-targeted CAR T-cell therapy due to reduction or loss of tumor CD19 expression. In June 2021, Aleta and Cancer Research UK announced a collaboration in which Cancer Research UK will fund, sponsor, and conduct the Phase 1/2a clinical trial of ALETA-001.