Cell Death or Cancer Growth: A Question of Cohesion

Technology Networks | November 20, 2019

Activation of CD95, a receptor found on all cancer cells, triggers programmed cell death - or does the opposite, namely stimulates cancer cell growth. Scientists from the German Cancer Research Center (DKFZ) have now shown that the impact of CD95 activation depends on whether there are isolated cancer cells or three-dimensional structures. Individual cells are programmed to die following CD95 activation. In contrast, CD95 activation stimulates growth in clusters of cancer cells, for example in solid tumors. This finding points to new ways of specifically transforming growth-stimulating signals into cell death signals for the cancer cells. The receptor protein CD95 is exposed on the surface of all cancer cells like small antennae. Activation of the receptor by the CD95 ligand (CD95L) triggers apoptosis in the cancer cell - or the exact opposite: "We studied various types of cancer tissue and found that CD95 activation usually stimulates tumor growth under natural conditions," remarked Ana Martin-Villalba, who has been conducting research at DKFZ on the role of CD95 for many years now. She was the first to describe the cancer-promoting effect of CD95 in glioblastomas (malignant brain tumors).

Spotlight

Among the major superpowers of our stem cells is their ability to self renew. Stem cells can also sense damaged cells and tissues and send signals that promote self-healing. In this mini-episode, Dr. Hyman speaks with Dr. William Li about the things that both enhance, and impair, our body’s regenerative abilities, including our diet. Dr. Li shares information on which foods have been scientifically proven to activate our body’s stem cells.

Spotlight

Among the major superpowers of our stem cells is their ability to self renew. Stem cells can also sense damaged cells and tissues and send signals that promote self-healing. In this mini-episode, Dr. Hyman speaks with Dr. William Li about the things that both enhance, and impair, our body’s regenerative abilities, including our diet. Dr. Li shares information on which foods have been scientifically proven to activate our body’s stem cells.

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INDUSTRIAL IMPACT

Athersys Amends Securities Purchase Agreement in Connection with Recent Registered Direct Offering

Athersys, Inc. | September 26, 2022

Athersys, Inc. a regenerative medicine company developing MultiStem® for critical care indications, announced that it has entered into amended agreements to extend the exercise period of the warrants that were issued as part of a registered direct offering that closed on August 17, 2022, among other changes, and to issue additional warrants to the same warrant holder, a healthcare-focused U.S. institutional investor. The Purchase Agreement contains certain restrictions that, subject to certain exceptions, prohibit the Company from issuing its common stock in certain variable rate transactions for a period of 180 days following the Closing Date. The Purchase Agreement also gives the Purchasers the right to participate in certain future offerings of the Company in an amount of up to 30 percent in the aggregate of any offered securities during the 12 months following the Closing Date. On September 22, 2022, the Company entered into an amendment to the Purchase Agreement with the Purchasers to, among other things, (i) extend the exercise period of the Initial Warrants from five years to seven years after the six-month anniversary of the Closing Date (the “Warrant Amendment”), (ii) reduce the Standstill Period from 180 days to 150 days following the Closing Date, (iii) reduce the term and amount of the Participation Right from twelve months to six months following the Closing Date and from 30 percent to 20 percent in the aggregate of any offered securities, respectively, and (iv) require the Purchasers, subject to certain conditions, to participate in the event the Company proposes to offer and sell shares of offered securities during the six months following the Closing Date to investors primarily for capital raising purposes. In return, Athersys issued to the same warrant holder additional warrants that are exercisable for an aggregate of 2,000,000 shares of common stock and have an exercise price of $6.3850 for a seven-year period after the six-month anniversary of the date of issuance. A more detailed discussion of the amendments is contained in a Current Report that Athersys filed on September 22, 2022 with the U.S. Securities and Exchange Commission on Form 8-K. “We are pleased to have entered into this amendment with our new major investor which provides more financial flexibility going forward as well as a commitment for the investor that recently invested $12 million in Athersys to participate in future financings if requested. As Athersys continues to pursue licensing and other business development opportunities for our proprietary technology this amendment can help facilitate future transactions with financial and strategic investors. We are fortunate to have established a strong relationship with a prominent healthcare focused institutional investor that embraces the value of our MultiStem cell therapy and is responsive to our priorities,” Dan Camardo, Chief Executive Officer of Athersys “I am also pleased with progress we’ve made in our business transformation and I look forward to updating shareholders during a conference call to be held the week of October 3rd,” he added. Athersys intends to issue a separate news release that will provide further information on the date and time of the call, as well as instructions regarding how to participate. About MultiStem® MultiStem® cell therapy is a patented regenerative medicine product in clinical development that has shown the ability to promote tissue repair and healing in a variety of ways, such as through the production of therapeutic factors in response to signals of inflammation and tissue damage. MultiStem therapy’s potential for multidimensional therapeutic impact distinguishes it from traditional biopharmaceutical therapies focused on a single mechanism of benefit. The therapy represents a unique “off-the-shelf” stem cell product that can be manufactured in a scalable manner, may be stored for years in frozen form, and is administered without tissue matching or the need for immune suppression. Based upon its efficacy profile, its novel mechanisms of action, and a favorable and consistent tolerability demonstrated in clinical studies, we believe that MultiStem therapy could provide a meaningful benefit to patients, including those suffering from serious diseases and conditions with unmet medical need. About Athersys Athersys is a biotechnology company engaged in the discovery and development of therapeutic product candidates designed to extend and enhance the quality of human life. The Company is developing its MultiStem® cell therapy product, a patented, adult-derived “off-the-shelf” stem cell product, initially for disease indications in the neurological, inflammatory and immune, and other critical care indications and has several ongoing clinical trials evaluating this potential regenerative medicine product. Athersys has forged strategic partnerships and a broad network of collaborations to further advance MultiStem cell therapy toward commercialization.

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INDUSTRIAL IMPACT

QIAGEN and Neuron23 Partner to Develop Next-Generation Sequencing Companion Diagnostic for Novel Parkinson’s Disease Drug

QIAGEN and Neuron23™ | September 15, 2022

QIAGEN and Neuron23 Inc., an early stage biotechnology company focused on developing precision medicines for genetically defined neurological and immunological diseases, announced the signing of an agreement to develop a companion diagnostic for Neuron23’s brain penetrant leucine-rich repeat kinase inhibitor for Parkinson’s disease. Under the new Master Collaboration Agreement, QIAGEN will develop and validate a clinical trial assay that will detect a combination of biomarkers discovered by Neuron23 that together predict the responsiveness of Parkinson’s disease to a LRRK2 inhibitor. The partnership will support the clinical development of Neuron23’s drug candidate that is currently in the late stages of preclinical development. Subject to further clinical development, the agreement also covers options for the future development of additional companion diagnostics. Neuron23 joins a group of more than 25 leading pharmaceutical and biotechnology companies who have reached master collaboration agreements with QIAGEN to develop and commercialize companion diagnostic tests for their drug candidates – a deep pipeline of potential future products to advance precision medicine for the benefit of patients around the world. The assay for this collaboration will be integrated into a next-generation sequencing workflow that leverages QIAGEN’s Sample to Insight capabilities, including instrumentation, IVD sample preparation, library preparation and bioinformatics. The workflow is planned to be developed using the NextSeqTM 500 System as part of the NGS strategic collaboration between QIAGEN and Illumina. Based on Neuron23’s artificial intelligence (AI)-enabled drug discovery and biomarker platform, it will target a complex signature of 50 single nucleic polymorphisms for U.S. and European populations and eventually additional SNPs that are prevalent in Asian populations. “The collaboration with Neuron23 shows the rapid momentum precision medicine is gaining in disease areas outside oncology. Our expertise in blood- and NGS-based molecular testing from Sample to Insight will enable Neuron23 to run a clinical trial for a drug candidate that may have the potential to modify the course of an inexorable neurodegenerative disease in a genetically defined population.” Jonathan Arnold, Vice President, Head of Oncology and Precision Diagnostics, at QIAGEN “This collaboration combines the leading expertise of Neuron23 in drug discovery, data science, and machine learning with QIAGEN’s long-standing experience and global leadership in companion diagnostic development. QIAGEN’s blood-based test will help to identify patients with Parkinson’s disease who are likely to respond to Neuron23’s LRRK2 inhibitor. The development of a companion diagnostic identifying this sub-population of Parkinson’s disease patients will de-risk the clinical development of Neuron23’s LRRK2 inhibitor and help identify individuals who may benefit from this disease-modifying therapy. We are excited to be working with an industry leader on the first companion diagnostic developed for Parkinson’s disease,” said Nancy Stagliano, Ph.D., CEO of Neuron23. No laboratory tests are currently available for the diagnosis of non-genetic cases for Parkinson’s disease. Usually, the disease is diagnosed based on medical history and neurological examination. Although no cure currently exists for Parkinson’s disease, therapies are used to alleviate some symptoms. LRRK2 is a complex, multidomain protein found in neurons and many tissues and cell types throughout the body. Mutations in the LRRK2 gene are one of the most common causes of familial Parkinson’s disease and individuals who inherit gain of function mutations in LRRK2 are clearly at higher risk to develop the disease in later life. Additionally, there is emerging evidence that LRRK2 may play a role in a subset of the larger population of patients with non-familial Parkinson’s disease. Recent investigations have shown that small-molecule LRRK2 inhibitors can be neuroprotective, suggesting that therapies targeting LRRK2 could be beneficial in a larger population of patients. QIAGEN is a pioneer in precision medicine and the global leader in collaborations with pharmaceutical and biotechnology companies to co-develop companion diagnostics, which detect clinically relevant genetic abnormalities to provide insights that guide clinical decision-making in diseases such as cancer. QIAGEN has an unmatched depth and breadth of technologies from NGS to polymerase chain reaction and digital PCR for companion diagnostic development. QIAGEN has ten PCR based companion diagnostic indications that are FDA approved, including therascreen EGFR for non-small cell lung cancer, therascreen KRAS for colorectal cancer and NSCLC, therascreen FGFR for urothelial cancer, therascreen PIK3CA for breast cancer based on tissue or plasma samples and the therascreen BRAF kit for colorectal cancer. About QIAGEN QIAGEN N.V., a Netherlands-based holding company, is the leading global provider of Sample to Insight solutions that enable customers to gain valuable molecular insights from samples containing the building blocks of life. Our sample technologies isolate and process DNA, RNA and proteins from blood, tissue and other materials. Assay technologies make these biomolecules visible and ready for analysis. Bioinformatics software and knowledge bases interpret data to report relevant, actionable insights. Automation solutions tie these together in seamless and cost-effective workflows. QIAGEN provides solutions to more than 500,000 customers around the world in Molecular Diagnostics, Applied Testing, Pharma and Academia. As of June 30, 2022, QIAGEN employed more than 6,100 people in over 35 locations worldwide. About Neuron23™ Neuron23™ Inc. is an early stage biotechnology company focused on developing precision medicines for genetically defined neurological and immunological diseases. Neuron23 combines recent advances in human genetics with a state-of-the-art artificial intelligence (AI)-enabled drug discovery and biomarker platform to advance therapeutics for devastating diseases. The Company’s focus areas are neurodegenerative diseases, neuroinflammatory diseases, and systemic autoimmune and inflammatory diseases. Founded in 2018, Neuron23 has assembled a world-class team of experts and entrepreneurs located in South San Francisco, CA.

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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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