Discovery of plant immune signaling intermediary could lead to more pest-resistant crops

Phys.org | November 26, 2019

A new actor in the immune system of plants has been identified. KAUST scientists have identified the protein MAP4K4 is needed to mount proper defenses against environmental pathogens. The discovery helps explain the tight control of immune signaling in plants and reveals targets in a molecular pathway that could be manipulated by crop breeders. "Our findings are directly applicable to make plants more resistant to pathogens," says study author, Heribert Hirt, professor of plant science at KAUST's Center for Desert Agriculture. MAP4K4 (short for mitogen-activated protein kinase kinase kinase kinase 4) is a well-established player in human immunity and inflammation, but its role in plant disease resistance was unknown. Hirt and his collaborators stumbled on it during a large screen for proteins involved in signal transduction in the weedy thale cress Arabidopsis. By studying mutant plants that lack a working copy of MAP4K4, Hirt's team then drilled down into the core functions of this protein.

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Living with cancer is about dealing with the unknown. It is about trying to grasp the news and starting to understand its life-changing effect. It is about wondering if the treatment is working and whether the side effects will go away soon. It is about questioning whether anything else can be done to overcome this illness. And it is about figuring out what life will be like when treatment is over while having hope for the future.

Spotlight

Living with cancer is about dealing with the unknown. It is about trying to grasp the news and starting to understand its life-changing effect. It is about wondering if the treatment is working and whether the side effects will go away soon. It is about questioning whether anything else can be done to overcome this illness. And it is about figuring out what life will be like when treatment is over while having hope for the future.

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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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MEDTECH

Bionaut Labs Closes $43M in Series B Led by Khosla Ventures to Advance First-in-Class Micro-Robotic Technology and Remove Barriers

Bionaut Labs | November 29, 2022

Bionaut Labs, the company that uses microscale robots to revolutionize the treatment of central nervous system diseases and disorders, announced $43.2M in a Series B round of financing led by Khosla Ventures, bringing the company’s total financing raised to date to $63.2 million. Also participating in the round are new investors Deep Insight, OurCrowd, PSPRS, Sixty Degree Capital, Dolby Family Ventures, GISEV Family Ventures, What if Ventures, Tintah Grace and Gaingels, along with all existing investors - Upfront Ventures, BOLD Capital Partners, Revolution VC, and Compound. Many diseases of the brain and central nervous system are hard to treat because it is difficult to deliver therapeutics beyond the blood-brain barrier and reach deep locations in the midbrain with precision. Through magnetic propulsion, Bionauts™ can navigate the depths of the human body to deliver drugs locally, generating efficacy and avoiding side effects and toxicity from systemically delivered drugs. By reaching the midbrain safely through novel routes, Bionaut Labs aims to develop solutions to treat the most debilitating conditions including Parkinson’s disease and Huntington's disease, malignant glioma and hydrocephalus. Funds will be used to advance clinical development of the company’s lead programs against malignant glioma brain tumors and Dandy-Walker Syndrome (a rare pediatric neurological disorder). Funds will also support further development of its proprietary Bionaut™ treatment platform, allowing future expansion of clinical targets and progression through Bionaut’s two accelerated FDA designations. Bionaut Labs will release major pre-clinical data packages from IDE and IND enabling studies in 2023, with the goal of initiating human clinical trials in 2024. “There has been a dearth of innovation around treatments for conditions that cause tremendous suffering, in large part because past failures have discouraged even the best of researchers. Bionaut Labs remains committed to finding new ways to treat these devastating diseases, which are long overdue for a breakthrough.” Michael Shpigelmacher, co-founder and CEO, Bionaut Labs Bionaut Labs is co-founded by two robotics entrepreneurs, Michael Shpigelmacher and Aviad Maizels, who previously co-founded PrimeSense, the company that developed the facial recognition tech behind iPhone’s FaceID. Its leadership and medical team consists of experts across robotics, neuroscience, biology and drug development. “We are extremely excited about the transformative potential Bionaut presents in treating debilitating neurological disorders,” said Vinod Khosla, founder of Khosla Ventures. “Anatomically precise treatment will make traditionally-used methods seem archaic, and Bionaut is at the forefront of this movement.” “Bionaut Labs tackles a complex pharmaceutical problem which many companies have failed to address in the past,” said Giammaria Giuliani, director of the GISEV Family Office. “As pioneers of micro-robotics for CNS treatment, the company enjoys a strong first-mover advantage and carries great promise.” As neurodegeneration continues to grow in prevalence in the aging global population, Bionaut Labs offers unprecedented therapeutic access to the brain and other hard-to-reach locations in the body, diagnosing and treating diseases that were previously unreachable. Bionaut Labs will transform the way the biopharmaceutical industry develops treatments by offering a mechanism to engineer the therapeutic index for optimal efficacy and safety. About Bionaut Labs Bionaut Labs is a biotech company pioneering precision micro-technology with the deployment of microscale robots to remove the barriers of localized treatment and detection of diseases. Magnetic propulsion-controlled Bionauts navigate to deep locations in the human body and brain safely and precisely through non-linear 3D trajectories, making Bionaut Labs the first to access the midbrain through previously inaccessible anatomical routes. Bionauts can perform localized treatment, detection and precise medical procedures to deliver outcomes that were previously unattainable. The FDA has granted Bionaut Labs a Humanitarian Use Device designation for BNL-201, a micro-robot design to treat Dandy Walker Malformation, and an Orphan Drug Designation for BNL 101, a drug-device combination for treatment of malignant glioma.

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INDUSTRIAL IMPACT

BioConsortia Showcases Breakthrough Microbial Products and Pipeline of Innovation

BioConsortia, Inc. | September 05, 2022

BioConsortia’s innovative microbial products and technical capabilities were on full display August 30th at its Davis, CA headquarters in an investor-focused Technology Showcase event. BioConsortia demonstrated rapid advancements in microbial product and pipeline developments for reducing nitrogen fertilizers, controlling soil pests and plant diseases for larger and better-quality crop yields, as well as protecting crops post-harvest to avoid food waste, while minimizing environmental impact and protecting our planet. The Showcase event reintroduced CRIMSON™ fungicide and biostimulant ZAFFRE™, two products currently awaiting final registrations, and highlighted BioConsortia’s new fungicides, nematicides and nitrogen fixing products that are progressing through registration and commercialization and moving into evaluation with potential partners, as follows: NO-NEM™ bionematicide advances: BioConsortia highlighted progress in bringing novel, safe and effective nematocidal microbes to market. Experts estimate global crop losses of $125 billion or 14% of crop value each year. Currently available chemical controls like methyl bromide, organophosphates and carbamates have an unacceptable level of toxicity to non-target organisms and are being withdrawn from use. NO-NEM is BioConsortia’s first nematicide product heading into full development phase. It has shown excellent performance against economically important pests in row crops, as well as fruits and vegetables, such as soybean cyst nematodes and root knot nematodes. “Today we highlight the breadth of innovations developed to replace chemical crop inputs with superior microbe-based solutions for nitrogen fixing, disease control, nematode control, crop yields and post-harvest food safety. The recent progress of our pipeline – including some exciting technology breakthroughs - means we are ready to advance multiple major products into the commercialization phase with marketing partners.” Marcus Meadows-Smith, CEO of BioConsortia R&D Pipeline Expanded through Technical Innovation Additions to BioConsortia’s R&D pipeline aim to leapfrog currently available microbial products, providing improved efficacy, increased shelf-stability, and reduced field use rates, as follows Leveraging GenePro™ microbe editing platform for nitrogen-fixing breakthroughs: BioConsortia’s proprietary genomics and gene-editing platform, GenePro™, facilitates the discovery and engineering of a wide diversity of microbes faster and more efficiently. BioConsortia’s scientists affirmed GenePro has resulted in the discovery of novel genetic components driving nitrogen-fixation. BioConsortia’s proprietary bacterial strains fix nitrogen under conditions other N-fixing strains will not. This discovery validates the company’s position as a leader in microbe-derived alternatives for agriculture, has resulted in proprietary intellectual property, and will continue to drive our research focus. Expanding library through AMS: BioConsortia’s patent-protected “AMS” - Advanced Microbial Selection™ platform uses evolutionary biology practices to find beneficial microbes that the plant has selected for specific gains. AMS underpins the breadth, depth, and success of BioConsortia’s product pipeline. The company announced the addition of more than 2000 rice diazotrophic microbial strains to its library, following a research program using AMS. This large addition to the library has greatly accelerated BioConsortia’s nitrogen-fixation project for rice, a crop with a paddy production model that represents a unique opportunity to impact the sustainability practices of both large and small growers of one of the world’s most fertilized crops. Novel Bactericide Project: BioConsortia also introduced a new project focused on optimizing microbes for the production of metabolites active against bacterial disease. Project leaders highlighted early technological success within this project – again reliant on the GenePro platform, which focuses on utilizing novel tools to address evolving bacterial disease resistance and increasing bacterial pest pressure resulting from climatic challenges and global trade flows. Novel Multi-spectrum Insecticide: Additionally, the company updated progress on a novel, developmental microbial active ingredient designed to deliver broad-spectrum control of both nematodes and critically important coleopteran and lepidopteran pests. The project aims to deliver a novel mode of action to support and extend crop trait lifecycles in the face of emerging insect resistance. Nematicide leads were originally characterized as strong root colonizers employing the company’s RhizoViz™ system, which uses proteins to visualize colonization robustness in different soils and environmental conditions. BioConsortia’s nematicide pipeline is now among the most expansive in agricultural research. “BioConsortia’s pipeline progress highlights the strengths of the company’s R&D platform – unique in the industry in terms of discovery of plant-affiliated microbes and their optimization as solutions for agriculture,” said Dr. Hong Zhu, Senior VP of Research and Development at BioConsortia. About BioConsortia BioConsortia, Inc. develops superior microbial products that protect plants, enhance fertility, and increase yields while improving the sustainability of agriculture for our environment. Pioneering the use of directed selection within microbial communities, our patented Advanced Microbial Selection process and cutting-edge GenePro genomics and gene-engineering platform enable us to predict, design, and unleash the natural power of microbes.

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