Anti-Opioid Pathway Discovered via Forward Genetics Approach with C. elegans

GEN | August 20, 2019

Scientists at Scripps Research in Florida report that they have discovered a biological system that manages cells response to opioid drug exposure. The team said its discovery offers new ideas for improving the safety of the one of the most effective, and most abused, group of pain medications. In a paper Genetic behavioral screen identifies an orphan anti-opioid system published in Science, lead authors Kirill Martemyanov, PhD, and Brock Grill, PhD, described how they designed and implemented a new approach using a nematode worm for decoding the genetic network that controls actions of opioids in a nervous system. “Opioids target μ-opioid receptor (MOR) to produce unrivaled pain management but their addictive properties can lead to severe abuse. We developed a whole animal behavioral platform for unbiased discovery of genes influencing opioid responsiveness. Using forward genetics in C. elegans, we identified a conserved orphan receptor, GPR139, with anti-opioid activity,” the investigators wrote. “GPR139 is coexpressed with MOR in opioid-sensitive brain circuits, binds to MOR and inhibits signaling to G proteins. Deletion of GPR139 in mice enhanced opioid-induced inhibition of neuronal firing to modulate morphine-induced analgesia, reward, and withdrawal. Thus, GPR139 could be a useful target for increasing opioid safety. These results also demonstrate the potential of C. elegans as a scalable platform for genetic discovery of GPCR signaling principles.”

Spotlight

Ever wonder how milk becomes cheese? We asked about the science and the microbes that go into this tasty food. This week on Reactions, we visit St. James Cheese Company in New Orleans to learn all about the chemistry of your favorite dairy product.

Spotlight

Ever wonder how milk becomes cheese? We asked about the science and the microbes that go into this tasty food. This week on Reactions, we visit St. James Cheese Company in New Orleans to learn all about the chemistry of your favorite dairy product.

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INDUSTRIAL IMPACT

Alloy Therapeutics Raises $42 Million Series D Financing to Accelerate Discovery Technology Development Across Biologic Modalities

Alloy Therapeutics, Inc. | October 04, 2022

Alloy Therapeutics, a biotechnology ecosystem company, has closed $42 million in Series D financing led by its existing investors 8VC and Mubadala Capital and joined by return investors Thiel Capital, Presight Capital, Founders Fund, and other unnamed family offices and sovereign wealth funds. Alloy will use proceeds from the Series D financing to further support the drug discovery community with new pre-competitive drug discovery technologies in new biologic modalities and new partnership models designed to fuel innovation. Since Alloy’s Series C fundraise in March 2021, Alloy has expanded from its foundational antibody discovery technologies and discovery services into T-cell receptors with the launch of its Keyway TCR Discovery division, and genetic medicines through its collaboration with Dr. Sudhir Agrawal, the inventor of gapmer technology. Alloy has further expanded with three new research sites, in Basel, CH; Athens, GA; and San Francisco, CA. “After three years of hard work and planning, we were proud to formally launch Keyway TCR Discovery in January 2022. We envision a future in 20 years where engineered TCRs and TCR mimics are as successful a modality as monoclonal antibodies are today. Keyway believes this is possible by providing unrestricted access to enabling technologies and discovery services without pharma having to spend billions of dollars to acquire companies for proprietary technologies and people.” Dongxing Zha, CEO of Keyway and Alloy’s CTO for TCR Modalities In response to growing engagement from partners, Alloy will further leverage its Series D funds to continue to invest in expanded offerings across all six of its modalities. These will support the drug discovery community in the pursuit of multi-modal therapeutics while reducing or eliminating stacked downstream payments. Through its affiliated venture studio, 82VS, Alloy supports scientist-entrepreneurs with seamless access to its cutting-edge technologies and discovery services. 82VS companies are often the first customers of Alloy’s innovations, having full access to the Alloy suite of technologies and discovery services to advance the best drug candidates and invent new applications that can benefit the broader Alloy ecosystem and, ultimately, patients and their caregivers. To best serve the vast discovery needs of pharmaceutical companies, Alloy is pioneering an Innovation Subscription offering that gives its collaborators access to all current and future Alloy technology platforms for one flat, annual fee with no milestones or royalties. Partners benefit from Alloy as an ever-growing source of pre-competitive, foundational discovery technology. Alloy also supports complementary CROs, CDMOs and other discovery and development service providers as a critical part of the collaborative ecosystem to empower pharma in its mission to cure disease. In this subscription model, Alloy provides a new home for promising pre-competitive technologies and academic breakthroughs that have traditionally been underfunded or unavailable to all. “Our Innovation Subscription model is available now as an exciting next step in furthering our collaborative mission and unlocking the potential for sharing foundational, pre-competitive drug discovery technologies with the global drug discovery community,” said Alloy Therapeutics Chief Executive Officer and Founder Errik Anderson. “Including this financing, Alloy will have invested hundreds of millions of dollars in innovation that the largest pharma companies can access through a flat, annual subscription with no additional milestones or royalties. Emerging biotech and academics can access our tech through collaboration and more traditional and creative structures. Combined with the reinvestment of 100% of our revenue, including our subscription revenue, back into innovation and access to innovation, Alloy is a new for-profit business model that plays for the collective long game in a non-zero-sum way. The value of a subscription goes up every year, while the fees stay flat or even will decrease with scale. We price this so a single avoided royalty will pay for the entire platform access over a 20-plus-year period. We are grateful for our longstanding investors for supporting this vision of arming the drug discovery industry with the tools they need to discover and develop the best medicines for patients more quickly.” Alloy launched in 2017 to democratize foundational, pre-competitive technologies and capabilities for the discovery of therapeutic biologics and has since grown with over 130 partners across academia, biotech, and large biopharma. Its first platform was the ATX-Gx™, a suite of transgenic mouse strains for human antibody discovery that was originally in-licensed from a major pharma company and made broadly available to the drug discovery ecosystem by Alloy, with open access to newly introduced strains. Through its DeepImmune™ Antibody Discovery services, Alloy helps partners find the best therapeutic antibody candidates against targets of interest, by deploying a bespoke blend of its proprietary in vivo, in vitro, and in silico technologies and workflows. In 2022, Alloy launched Keyway™ TCR Discovery as its second fully integrated technology and services offering for the discovery of therapeutic engineered TCRs and TCR mimics. “Alloy has successfully expanded its flagship discovery offering in antibodies to multiple promising modalities to better serve the global drug discovery community,” said Alaa Halawa, Head of Mubadala Capital’s US Ventures business, which first backed Alloy as an investor in its Series C financing. “We are proud to partner with the company as it executes on its promise of enabling scientists through the development of transformative drug discovery technologies. We look forward to seeing how the partnership with large pharma partners and other venture firms will leverage Alloy’s platform to enable their therapeutic discovery teams and emerging startups to advance the best medicines.” About Alloy Therapeutics aAlloy Therapeutics is a biotechnology ecosystem company empowering the global scientific community to make better medicines together. Through a community of partners across academia, biotech, and the largest biopharma, Alloy democratizes access to pre-competitive tools, technologies, services, and company creation capabilities that are foundational for discovering and developing therapeutic biologics across six modalities, including antibodies, TCRs, genetic medicines, peptides, cell therapies, and drug delivery. Partners may access all current and future technologies for a flat annual fee through Alloy’s Innovation Subscriptions offering. As a reflection of Alloy’s relentless commitment to the scientific community, Alloy reinvests 100% of its revenue in innovation and access to innovation. About Alloy’s Antibody Discovery Offering Alloy’s first foundational platform, the ATX-Gx™ mice, is a suite of proprietary transgenic mice strains for human therapeutic antibody discovery, which can be accessed in your lab or through DeepImmune™ Antibody Discovery. This service integrates Alloy’s full complement of proprietary in vivo, in vitro, and in silico discovery and optimization technologies into one comprehensive service offering for fully human monoclonal and bispecific antibody discovery. The technologies and protocols can be replicated in a partner’s organization through a platform transfer and as part of an Alloy Innovation Subscription. Alloy is a leader in bispecific antibody discovery and engineering services, utilizing its proprietary ATX-CLC common light chain platform integrating novel transgenic mice and phage display. About Keyway™ TCR Discovery In 2022, Alloy launched Keyway™ TCR Discovery, Alloy's second fully integrated platform and service offering. Led by a team of TCR therapeutic pioneers and experts and leveraging the full resources of the Alloy ecosystem, Keyway provides comprehensive proprietary technology and capabilities for end-to-end discovery of TCR mimics and engineered TCRs, which includes production and quality control of MHC/peptide complexes, biophysical characterization, specificity testing, reformatting, and engineering, affinity maturation, and in vivo and in vitro preclinical testing. Partners may access Keyway's technology and capabilities through a standard or bespoke one-stop-shop discovery campaign, platform transfer, or Innovation Subscription.

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CELL AND GENE THERAPY

Hamilton and BioFluidica Pen Next Generation Liquid Biopsy Platform Co-Marketing Agreement

BioFluidica, Inc. | September 28, 2022

Biofluidica, Inc., and Hamilton Company, announced a co-marketing agreement to bring advanced Liquid Biopsy capabilities to laboratories worldwide. Biofluidica has developed the next-generation liquid biopsy platform, enabling Hamilton liquid handlers to process biological samples to isolate extremely rare circulating tumor cells, circulating Leukemic cells, fetal cells, cfDNA, and exosomes. The Biofluidica platform, LiquidScan™, integrates seamlessly into the Hamilton pipetting robots. The high precision fluid control provided by the Hamilton automated pipetting channels is designed to avoid processing loss using the Biofluidica proprietary closed-loop pipetting interface with the Biofluidica microfluidic biomarker selection chips. This announcement represents early commercialization for BioFluidica and a unique alliance for Hamilton Company. The STARlet offers a custom application-configurable liquid handling robot with sensitive programmable pneumatic features that enable walk-away automation for precision biological procedures. LiquidScan utilizes these features to isolate and enrich rare biomarker populations directly from biological samples such as a blood draw potentially replacing the need for surgical biopsies and making testing available for cancer types not previously amenable to surgical biopsy. "LiquidScan is a novel platform that enhances the ability to perform diagnostic testing applied to many diseases, including several types of cancer, prenatal diagnostics, stroke, and infectious diseases. We have worked with Hamilton to ensure seamless automation allowing for high-throughput and lower-cost testing than current surgical biopsy procedures. There is a win-win scenario here for patients, physicians, and the healthcare system. Because LiquidScan uses a standard blood draw, and non-invasive screening, patients can receive closer monitoring of treatment regimens, and physicians can attain higher quality and earlier patient results. Expensive and time-consuming surgical procedures can be removed from the health-care system." Rolf Muller, BioFluidica CEO About Hamilton Hamilton is a leading global manufacturer, providing automated liquid handling workstations and laboratory automation technology to the scientific community. With a focus on innovative design, Hamilton products incorporate patented liquid handling technologies into a portfolio that includes liquid handling platforms, standard application-based solutions, small devices, consumables, and OEM liquid handling solutions. Known for advancing life science, clinical diagnostics, forensics, and biotechnology industries, Hamilton products offer reliability, performance, and flexibility. Ensuring a continuous commitment to quality, Hamilton utilizes state-of-the-art manufacturing at production facilities in Reno, Nevada, and Bonaduz, Switzerland and has earned a global ISO 9001 certification. Privately held, Hamilton maintains headquarters in Reno, Nevada; Franklin, Massachusetts; and Bonaduz, Switzerland, along with subsidiary offices throughout the world. About BioFluidica BioFluidica Inc. is a privately held biotechnology company that has developed a revolutionary liquid biopsy platform.

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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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