Algorithm Hunts for Anomalies in Gene Expression Data

Technology Networks | November 28, 2019

Computational biologists at Carnegie Mellon University have devised an algorithm to rapidly sort through mountains of gene expression data to find unexpected phenomena that might merit further study. What's more, the algorithm then re-examines its own output, looking for mistakes it has made and then correcting them. This work by Carl Kingsford, a professor in CMU's Computational Biology Department, and Cong Ma, a Ph.D. student in computational biology, is the first attempt at automating the search for these anomalies in gene expression inferred by RNA sequencing, or RNA-seq, the leading method for inferring the activity level of genes. The researchers report that they have already have detected 88 anomalies — unexpectedly high or low levels of expression of regions within genes — in two widely used RNA-seq libraries that are both common and not previously known. "We don't yet know why we're seeing those 88 weird patterns," Kingsford said, noting that they could be a subject of further investigation. Though an organism's genetic makeup is static, the activity level, or expression, of genes varies greatly over time. Gene expression analysis has thus become a major tool for biological research, as well as for diagnosing and monitoring cancers.

Spotlight

A new way of thinking and working has evolved for the discovery of therapeutic antibodies. Until recently, large numbers of antibodies were generated, only for a relatively small fraction to be sampled and engineered for further lead generation. Now, Array SPR (Surface Plasmon Resonance) facilitates a paradigm shift in antibody screening, enabling higher information content assays to be conducted earlier in the research pipeline to streamline lead selection. This essentially combines screening and detailed characterization in the same step.

Spotlight

A new way of thinking and working has evolved for the discovery of therapeutic antibodies. Until recently, large numbers of antibodies were generated, only for a relatively small fraction to be sampled and engineered for further lead generation. Now, Array SPR (Surface Plasmon Resonance) facilitates a paradigm shift in antibody screening, enabling higher information content assays to be conducted earlier in the research pipeline to streamline lead selection. This essentially combines screening and detailed characterization in the same step.

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CELL AND GENE THERAPY

Biocytogen Enters into Antibody Agreement with ADC Therapeutics

Biocytogen | November 28, 2022

Biocytogen Pharmaceuticals Co., Ltd. announced that it has entered into an evaluation and option agreement with ADC Therapeutics SA. Biocytogen will grant ADC Therapeutics a license to evaluate Biocytogen’s proprietary antibodies against three tumor targets, with an option to license selected antibodies at a later date for global ADC development and commercialization. Biocytogen reserves all global rights for these antibodies beyond ADC development. Biocytogen will receive an upfront payment. For each option exercised, Biocytogen will be entitled to an option-exercise fee, and development and commercial milestone payments, which potentially total tens of millions of US dollars, as well as single-digit royalties on net sales. Under the agreement, Biocytogen will provide ADC Therapeutics with monoclonal and/or biparatopic antibodies directed against three tumor targets, generated through Biocytogen’s Project Integrum. ADC Therapeutics will carry out feasibility studies and be responsible for further development and commercialization of the ADC products if the company exercises an option. “ADC Therapeutics is a leader in the development and commercialization of ADCs. We believe this collaboration with ADC Therapeutics will underscore the value of Biocytogen’s proprietary antibody discovery and screening platforms. We’ve been dedicated to expanding the possibilities of antibody-based therapeutics in disease treatment, through the exploration of new types of targets and modalities through Project Integrum. The combination of Biocytogen’s strength in antibody development with ADC Therapeutics’ expertise and track record in payload and linker technology may lead to the generation of novel ADC medicines for unmet medical needs in the future.” Dr. Yuelei Shen, President and CEO of Biocytogen “We are pleased to enter this collaboration with Biocytogen as we continue expanding our toolbox to realize the full potential of our ADC platform,” said Patrick van Berkel, PhD, Chief Scientific Officer of ADC Therapeutics. “We look forward to evaluating the fully human antibodies from Biocytogen’s proprietary discovery platform, which have the potential to accelerate the development of our novel ADCs.” About Biocytogen Biocytogen is a global biotechnology company that drives the research and development of novel antibody-based drugs with innovative technologies. Using its proprietary RenMabTM /RenLite® mice platforms for fully human monoclonal and bispecific antibody development, Biocytogen has integrated its in vivo drug efficacy screening platforms and strong clinical development expertise to streamline the entire drug development process. Biocytogen is undertaking a large-scale project to develop first-in-class and/or best-in-class antibody drugs for more than 1000 targets, known as Project Integrum. This project has resulted in 28 drug co-development agreements and 16 RenMiceTM licensing agreements with companies around the world, including several partnerships with multinational pharmaceutical companies (MNCs). The company's pipeline includes 12 core products, among which two products are in phase II multi-regional clinical trials and two products are in phase I. Headquartered in Beijing, Biocytogen has branches in Haimen Jiangsu, Shanghai, Boston, USA and Heidelberg, Germany. About ADC Therapeutics ADC Therapeutics is a commercial-stage biotechnology company improving the lives of those affected by cancer with its next-generation, targeted antibody drug conjugates. The Company is advancing its proprietary PBD-based ADC technology to transform the treatment paradigm for patients with hematologic malignancies and solid tumors. ADC Therapeutics’ CD19-directed ADC ZYNLONTA is approved by the FDA for the treatment of relapsed or refractory diffuse large b-cell lymphoma after two or more lines of systemic therapy. ZYNLONTA is also in development in combination with other agents. In addition to ZYNLONTA, ADC Therapeutics has multiple ADCs in ongoing clinical and preclinical development.

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INDUSTRIAL IMPACT

FogPharma Announces $178 Million Series D Financing to Advance Pipeline of First-in-Class Helicon Polypeptide Therapeutics Targeting

FogPharma | November 22, 2022

FogPharma®, a biopharmaceutical company pioneering a new class of precision medicines that could ultimately prove applicable to the vast majority of therapeutic targets, including those previously considered “undruggable,” today announced a $178 Million Series D financing. The financing round includes new investors ARCH Venture Partners, Milky Way Investments and Fidelity Management & Research Company and existing investors VenBio Partners, Deerfield Management, GV, Cormorant Asset Management, funds and accounts advised by T. Rowe Price Associates, Inc., Invus, Farallon Capital Management, HBM Healthcare Investments, Casdin Capital, and PagsGroup, also participated. Proceeds from the Series D financing will be used to advance and accelerate FogPharma’s growing pipeline of hyperstabilized α-helical polypeptide therapeutics, a proprietary new class of drugs designed to overcome the limitations of today’s precision medicines with broad applicability to the vast majority of disease targets and therapeutic areas. FogPharma’s lead Helicon polypeptide development candidate, FOG-001, a first-and-only-in-class direct TCF-blocking β-catenin inhibitor with potential applicability to significant cancer patient populations, is expected to enter clinical development in mid-2023. In addition, FogPharma is advancing other first-in-class programs against important, biologically validated cancer targets that have remained elusive to other approaches including TEAD, NRAS, Pan-KRAS, ERG and Cyclin E1. “FogPharma continues to make rapid progress on our moonshot mission to achieve universal druggability – a world where no targets are off-limits to medicine. We believe that Helicon polypeptides, a compelling new therapeutic modality, represent the future of precision medicine. We are thrilled by the support of our investors and will continue to build our platform capabilities, product pipeline which aims to address a significant percentage of cancer patient populations, and our phenomenal team across all levels as we aim to create one of the most impactful new classes of drugs in history.” Gregory Verdine, Ph.D., founder, chairman and chief executive officer of FogPharma In connection with the Series D Financing, Rick Klausner, M.D., has been appointed to FogPharma’s board of directors. In addition, Dr. Verdine has been appointed as chairman of the board. “The team at FogPharma is building an unprecedented new therapeutic modality and robust pipeline with the potential to make a meaningful difference in the lives of cancer patients,” said Dr. Klausner. “I am excited to join the board of directors and be part of something special – particularly at this important time as FogPharma continues to impressively scale its science, team, operations and infrastructure, with the goal of advancing its first Helicon polypeptide therapeutic into the clinic.” Dr. Klausner is currently the founder and chief scientist of Altos Labs and founder and chairman of Lyell Immunopharma. Dr. Klausner was founder and director of Juno Therapeutics and founder and director of GRAIL. He is also the chairman of Sonoma Biotherapeutics and co-founder and chairman of Lifemine Therapeutics. Previously, Dr. Klausner served as senior vice president, chief medical officer and chief opportunity officer of Illumina Corporation and as executive director for global health for the Bill and Melinda Gates Foundation. Dr. Klausner was appointed by Presidents Clinton and Bush as the eleventh director of the U.S. National Cancer Institute (NCI) between 1995 and 2001. Dr. Klausner served as chief of the Cell Biology and Metabolism Branch of the National Institute of Child Health and Human Development as well as a past president of the American Society of Clinical Investigation. He has served in senior advisory roles to the U.S., Norwegian, Qatari and Indian governments. About FogPharma’s Universal Druggability Platform and Helicon™ Polypeptide Therapeutics Existing drug classes are limited in both reach and applicability, with more than 80% of known human protein disease targets considered “undruggable” because they are beyond the reach of both antibodies and small molecules. FogPharma’s Helicon peptide drug discovery engine integrates directed evolution, proprietary α-helix conformational hyperstabilization chemistry, highly multiplexed drug optimization technology, artificial intelligence including deep learning and machine learning, structure-based drug discovery, cancer genomics and biology, and multiscale manufacturing to rapidly discover Helicon polypeptide therapeutics. This novel therapeutic modality combines the targeting strength and specificity of antibodies with the broad tissue distribution, intracellular target engagement and oral dosing optionality of small molecules to address the limitations of today’s precision medicines and reach the most difficult targets – achieving universal druggability. About FOG-001 FogPharma’s lead Helicon polypeptide development candidate, FOG-001, a first-and-only-in-class direct TCF-blocking β-catenin inhibitor. Dysregulation of the Wnt/β-catenin signaling pathway has been shown to occur in at least 20% of all human cancers. In the U.S. alone, FOG-001 has the potential to become a new treatment option for >1 million patients suffering from a broad range of intractable cancers. In biochemical and cellular studies, FOG-001 has been shown to potently, precisely and selectively disrupt the interaction of β-catenin with its obligate downstream transcription factor, TCF. Preclinical studies have demonstrated the ability of FOG-001 to cause tumor growth inhibition and regression by disrupting β-catenin-dependent signaling. FOG-001 is the inaugural member of FogPharma’s TCF-Catenix family of direct-acting β-catenin antagonists and combines key features that distinguish it from previously reported Wnt/β-catenin pathway modulators: FOG-001 acts inside the cell, where it directly binds the key oncogenic driver β-catenin; and FOG-001 blocks TCF-β-catenin engagement at the most downstream node in the canonical Wnt pathway, thus abrogating the signal transmission mechanism by which most, if not all, known Wnt pathway mutations are believed to drive oncogenesis. About FogPharma FogPharma is a biopharmaceutical company pioneering the discovery and development of Helicon™ polypeptides. Through this novel therapeutic modality, FogPharma aims to address the limitations of existing drug classes and achieve universal druggability – a world where no targets are off-limits to new medicines. Spun out of Harvard University by pioneering academic scientist and successful biotech company builder Dr. Gregory Verdine, FogPharma is advancing a broad pipeline of Helicon polypeptide therapeutics against important and biologically validated cancer targets that have remained elusive to other approaches, with the goal of providing new targeted treatment options for significant cancer patient populations. FogPharma is headquartered in Cambridge, Mass., and has raised more than $360 million to date from leading life sciences investors.

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INDUSTRIAL IMPACT

XtalPi and CK Life Sciences to collaborate in AI-empowered tumour vaccine research and development, opening a new paradigm for scientific innovation

XtalPi Inc. | November 25, 2022

XtalPi announced today that they are embarking on a strategic collaboration with CK Life Sciences, a member of the CK Hutchison Group. XtalPi and CK Life Sciences will leverage their respective expertise to jointly develop a novel AI tumour vaccine R&D platform to improve the discovery and design capabilities of tumour vaccines and accelerate the development of more vaccine types. The goal of this collaboration is to realize precision treatment for patients worldwide. According to public information, there were nearly 20 million newly diagnosed cancer patients worldwide in 2021, of which about 4.5 million cases came from China. Many cancer types lead to detrimental outcomes, with high morbidity and mortality, and there remains a large unmet clinical need. Tumour vaccines targeting different tumour neoantigens, tumour-associated antigens and tumour-specific antigens in patients can be designed for use as immunotherapy, to activate the patient's own specific immune responses. Currently, there are only two therapeutic tumour vaccines— sipuleucel-T for melanoma and Bacillus Calmette-Guérin for bladder cancer, as well as preventive tumour vaccines against human papillomavirus infection and hepatitis B infection approved by the U.S. Food and Drug Administration. Recently, several other tumour vaccines have entered clinical development and evidence of efficacy has begun to emerge. According to Mordor Intelligence, the global cancer vaccine market size was US$6.79 billion in 2021 and will increase at a compound annual growth rate of 11.53% from 2022 to 2026. The expected market size by 2026 will be approximately US$12 billion. Currently, the design and preclinical development process for tumour vaccines is complex and lengthy, hindering the efficiency and success rate of tumour vaccine research and development. Incorporating XtalPi's industry expertise in AI computation and robotic automation, this collaboration aims to build an AI tumour vaccine R&D platform that applies advanced AI algorithms and high-precision molecular modeling to predict and design a variety of tumour vaccines that can activate specific immune responses to kill tumours. The tumour vaccines will be screened and verified through automated experiments, and through integrating algorithmic feedback to optimise activity and efficacy, the platform is expected to generate preclinical tumour vaccine candidate compounds with robust immune activity. "As a company headquartered in the Hetao Shenzhen-Hong Kong Science and Technology Innovation Cooperation Zone, XtalPi is committed to realising the synergies between Shenzhen and Hong Kong by creating a new paradigm for innovation in the Greater Bay Area. Empowered by the latest technological advancements in automation, artificial intelligence is accelerating more innovative and diverse areas in drug research and development. Together with CK Life Sciences, we are committed to overcome conventional limitations and discover diverse applications for cutting-edge technologies. We believe the AI cancer vaccine platform jointly developed by CK Life Sciences and XtalPi will inspire the global scientific community to progress vaccine research and development and fast-track key development milestones for cancer vaccines. We are confident that this collaboration will significantly facilitate the scientific research exchange in the Greater Bay Area." Dr. Shuhao Wen, co-founder and chairman of XtalPi Dr. Melvin Toh, Vice President and Chief Scientific Officer of CK Life Sciences, comments: "The R&D of tumour vaccines is one of the key development directions of CK Life Sciences. The cooperation with XtalPi will apply XtalPi's AI algorithm, molecular modeling and automated experiments to speed up the R&D process, improve the success rate, and increase the efficacy of tumour vaccines." About XtalPi Founded in 2014, XtalPi founders recognized a common hurdle in drug development having to do with solid polymorphism, which could be successfully tackled with quantum physics predictions. Since then, XtalPi has maintained its focus on identifying and then attacking traditional bottlenecks in biopharmaceutical R&D through innovative technologies. Through considerable capital investments in automation and personnel, XtalPi now has four locations worldwide and employs approximately 1000 employees. XtalPi has engaged in collaboration research with nearly all top-20 pharmaceutical companies in the world. Its ID4 platform combines physics-based simulations with experimental validation and refinement, automation for rapid synthesis, and machine learning to continuously improve prediction accuracy and process efficiency. About CK Life Sciences CK Life Sciences is listed on the Stock Exchange of Hong Kong. Bearing the mission of improving the quality of life, CK Life Sciences is engaged in the business of research and development, manufacturing, commercialisation, marketing, sale of, and investment in, products and assets which fall into three core categories - nutraceuticals, pharmaceuticals and agriculture-related. CK Life Sciences is a member of the CK Hutchison Group.

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