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Vir Biotechnology to Host a Call on Sotrovimab’s Retained Activity Against the Omicron SARS-CoV-2 Variant – GlobeNewswire

Posted: December 10, 2021 at 2:35 am

SAN FRANCISCO, Dec. 07, 2021 (GLOBE NEWSWIRE) -- Vir Biotechnology, Inc. (Nasdaq: VIR) announced that Management will host a conference call at 8:30 am ET, Tuesday, December 7, 2021, to discuss new data that demonstrates sotrovimab retains activity against the full combination of mutations in the spike protein of the Omicron SARS-CoV-2 variant.

To access the call via telephone, please dial (833) 727-9519 (North America) or (830) 213-7696 (International), conference ID: 9894016.

A live webcast of the call can be accessed under Events & Presentations in the Investors section of the Vir website atwww.vir.bioand will be archived there for 30 days.

About Vir BiotechnologyVir Biotechnologyis a commercial-stage immunology company focused on combining immunologic insights with cutting-edge technologies to treat and prevent serious infectious diseases. Vir has assembled four technology platforms that are designed to stimulate and enhance the immune system by exploiting critical observations of natural immune processes. Its current development pipeline consists of product candidates targeting COVID-19, hepatitis B virus, influenza A and human immunodeficiency virus. For more information, please visitwww.vir.bio.

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Cyrus Biotechnology Announces $18M Financing and Acquisition of Orthogonal Biologics to Form an Integrated Software-Driven Pre-Clinical-Stage Drug…

Posted: December 10, 2021 at 2:35 am

SEATTLE--(BUSINESS WIRE)--Cyrus Biotechnology, Inc., a Seattle-based biotechnology firm with a proprietary software platform for biologics discovery, today announced the closing of a $18M Series B financing and acquisition of Orthogonal Biologics, a deep mutational scanning protein engineering spin-out from the University of Illinois at Urbana Champaign. The financing includes investments from OrbiMed Advisors, Trinity Ventures, Agent Capital, Yard Ventures, Washington Research Foundation (WRF), iSelect Fund, a leading Asian private equity firm, W Fund, family offices, and individual investors. Selecta Bioscience joined the financing as a strategic investor.

We are thrilled to bring together a range of experienced biotech investors from across the globe to support our move into independent drug discovery, said Cyrus CEO Lucas Nivon. Over the last four years we have worked with dozens of companies such as Janssen and other global pharmaceuticals to advance their biologics, honing and validating our algorithms in the process.

Erik Procko, formerly CEO at Orthogonal Biologics, added that, By merging our company with Cyrus we can create a unified biologics discovery platform, building on Cyruss years of software development and business relationships to create value across a range of indications where progress was previously impossible. In some cases progress has been stalled for decades, or an effective drug has never been discovered. We can change the progress of disease for many patients and, over time, in dozens of indications where our technology offers new opportunity and hope.

Cyrus is focusing the combined software-and-screening platform on the re-design of natural proteins to produce superior biologics of unique efficacy and safety, meeting unmet medical needs for a range of indications. The firm has initiated a variety of in-house and partnered programs during the past 12 months, and the Orthogonal acquisition now adds a broad-spectrum protein-based COVID-19 therapeutic and another biologic to the pipeline. Programs in autoimmunity are being carried out in partnership with Selecta Biosciences, announced earlier this year. Cyrus also previously announced its collaboration with The Broad Institute in next-generation CRISPR engineering for reduced immunogenicity.

Cyruss software platform is based on years of work in computational biophysics and the first software algorithms to computationally design entirely new proteins with the Rosetta software package developed by David Bakers lab at UW. On top of Rosetta, Cyrus incorporates proprietary AI algorithms and a range of bioinformatics and cheminformatics tools, cloud infrastructure, and rigorous benchmarking with internal and partnered data. This unified set of biologics discovery tools has helped advance a number of Cyruss partners molecules to pre-clinical development and IND. Orthogonal Biologics and Dr. Prockos laboratory at UIUC have developed a uniquely powerful deep mutational scanning system, with capabilities across a range of protein and cell types, to produce accurate and highly human-relevant data for protein engineering. These capabilities have been used to identify and patent an exhaustive set of ACE2 receptor variants which serve as SARS-CoV-2 decoys and have significant therapeutic value. A subset now validated in animal studies shows unique resistance to novel emerging COVID variants when compared with antibodies and other therapeutics. This combined set of capabilities allows Cyrus to identify novel, effective and safe biologics more rapidly than with existing methods commonly used in BioPharma.

Geeta Vemuri, founder and managing partner at Agent Capital added, Rosetta has been well-known for years in academia, and Cyrus has proven the power of its Rosetta-based platform as a software and services company. We are very excited to now apply those software and laboratory tools directly for Cyruss partners and in house drug discovery.

About Cyrus Biotechnology

Cyrus Biotechnology is a pre-clinical-stage biotech company combining computational and experimental protein design and screening to create novel biologics for serious unmet medical needs. Using this approach, Cyrus is developing an early pipeline of innovative programs in multiple indications. The Cyrus platform improves both the efficacy (binding affinity, aggregation propensity, solubility, and stability) and safety (binding specificity and immunogenicity) of natural proteins. Cyrus is also partnering with leading biotech and pharma companies and research institutes to bring collaborative programs forward from discovery to the clinic. Cyrus is based on core software from the lab of David Baker at the University of Washington. Cyrus has worked with over 90 industry partners. The company is based in Seattle, WA and financed by leading US and Asian biotech and tech investors including Orbimed, Trinity Ventures, Springrock, Agent Capital, iSelect, Yard Ventures, WRF, and Alexandria. For more information about Cyrus please visit https://cyrusbio.com/.

NOTICE: The information contained in this document is dated as of November 30, 2021. Cyrus Biotechnology, Inc. (the Company) disclaims any obligation to update such information after such date. This document contains forwardlooking statements reflecting the Companys current expectations that necessarily involve risks and uncertainties. Actual results and the timing of events may differ materially from those contained in such forward-looking statements due to a number of factors and the Company undertakes no obligation to revise or update any forward-looking statement to reflect events or circumstances after the issuance of this press release.

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GlaxoSmithKline, Vir Biotechnology Say COVID Therapy Effective Against Omicron Variant – TheStreet

Posted: December 10, 2021 at 2:35 am

GlaxoSmithKline (GSK) - Get GlaxoSmithKline Plc Reportand its U.S. partnerVir Biotechnology (VIR) - Get Vir Biotechnology, Inc. Reportsaid Tuesday that theirCOVID antiviral is effective against all mutations of the Omicron variant, sending shares in theSan Francisco-based drugmaker sharply higher in pre-market trading.

The pair said their COVID treatment, known as 'sotrovimab' -- which was approved for use in the United Kingdom earlier this month -- was found to have worked against the 37 different mutations in the spike protein of the Omicron variant in data published from a recently-completed study.

GlaxoSmithKline and Vir Bio also noted thatsotrovimabretained its 'in vitro activity' against key individual mutations of the Omicron variant, based on what it calledinitial preclinical data generated through "pseudo-virus testing".

Sotrovimab is the first monoclonal antibody to report preclinical data demonstrating activity against all tested SARS-CoV-2 variants of concern and interest to date, including Omicron, as well as the still prevalent and highly contagious Delta variant," said CEO George Scangos.

"Given the less than three-fold neutralization shift demonstrated in the pre-clinical pseudo-virus assay, we are confident that sotrovimab will continue to provide significant benefit for the early treatment of patients hoping to avoid the most severe consequences of COVID-19.

Vir Bio shares were marked 9.75% higher in pre-market trading Tuesday to indicate an opening bell price of $42.. each. GlaxoSmithKline's U.S.-listed shares edged 0.8% higher to $42.10 each.

The World Health Organization said Tuesday that it has identified 432 cases of the Omicron variant, over its 21 member states, as of December 6, adding that there isn't enough data as yet to determine if the variant will be more or less transmissible -- or indeed severe -- than previous mutations.

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Vir Biotechnology Stock (VIR): Why The Price Jumped Today – Pulse 2.0

Posted: December 10, 2021 at 2:35 am

The stock price of Vir Biotechnology Inc (NASDAQ: VIR) increased by over 11% today. Investors are responding positively to GlaxoSmithKline and Vir Biotechnology today announcing an update to preclinical data on bioRxiv1, a preprint server, demonstrating that sotrovimab, an investigational monoclonal antibody, retains in vitro activity against the full known Omicron spike protein, the new SARS-CoV-2 variant (B.1.1.529).

This preclinical data was generated through pseudo-virus testing of the combined known mutations of the Omicron variant, which included the maximum number of changes (37 mutations) identified to date in the spike protein. And these findings build on the initial preclinical data generated through pseudo-virus testing, provided last week, showing sotrovimab retained in vitro activity against key individual mutations of the Omicron variant, including those found in the binding site of sotrovimab. This data adds to the growing body of preclinical evidence demonstrating that sotrovimab retains activity against all tested variants of concern.

KEY QUOTES:

Sotrovimab is the first monoclonal antibody to report preclinical data demonstrating activity against all tested SARS-CoV-2 variants of concern and interest to date, including Omicron, as well as the still prevalent and highly contagious Delta variant. Given the less than three-fold neutralization shift demonstrated in the pre-clinical pseudo-virus assay, we are confident that sotrovimab will continue to provide significant benefit for the early treatment of patients hoping to avoid the most severe consequences of COVID-19.

George Scangos, Ph.D., Chief Executive Officer of Vir

From the outset of our collaboration with Vir we hypothesized that sotrovimab would have a high barrier to resistance and thus could deliver best-in-class potential for the early treatment of patients with COVID-19. These pre-clinical data demonstrate the potential for our monoclonal antibody to be effective against the latest variant, Omicron, plus all other variants of concern defined to date by the WHO, and we look forward to discussing these results with regulatory authorities around the world.

Dr. Hal Barron, Chief Scientific Officer and President R&D, GSK

Disclaimer: This content is intended for informational purposes. Before making any investment, you should do your own analysis.

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GRO Biosciences Announces Appointment of Bruce Beutel, PhD to Board of Directors and JP Morgan Health Care Conference Week Activities – BioSpace

Posted: December 10, 2021 at 2:35 am

BOSTON--(BUSINESS WIRE)-- GRO Biosciences Inc. (GRObio), an emerging biotechnology company leveraging groundbreaking science to expand the amino acid alphabet and deliver on the promise of protein therapeutics, today announced the appointment of Bruce Beutel, PhD to its Board of Directors and its upcoming participation and activity during J.P. Morgan Health Care Week in January 2022.

This press release features multimedia. View the full release here: https://www.businesswire.com/news/home/20211209005324/en/

GRObio appointed Bruce Beutel, PhD to its Board of Directors. (Photo: Business Wire)

GRObio appointed Bruce Beutel, PhD to its Board of Directors. Dr. Beutel is an expert in novel therapeutics and platform research, business development, and company creation. Over the course of his career, he has focused on strategy, vision, team building and value creation at the interface of science and business, particularly for emerging biotechnology companies. Dr. Beutel has held several C-level roles in multiple biotechnology companies including founding Chief Operating Officer and Chief Business and Strategy Officer at Dewpoint Therapeutics. He also has served in leadership roles at both Abbott and Merck. Dr. Beutel now serves as Venture Partner with Qiming Venture Partners USA. Dr. Beutel received his PhD in Molecular Biology from University of WisconsinMadison.

We are thrilled to have Bruce join our Board of Directors. His long-standing experience in building successful platform biotechnology companies will help ensure GRObios technology reaches its greatest potential, said Daniel J. Mandell, PhD, Co-Founder and Chief Executive Officer of GRO Biosciences. Bruces depth of experience from founding and leading biotechnology companies, to serving in business development, operations and strategy roles will be a great asset to GRObio as we continue to advance our platform, pipeline and partnerships.

GRObio at JPM

GRObio senior leadership will attend the J.P. Morgan Health Care Conference from January 10 14 and will participate in in-person meetings as well as virtual meetings via the Biotechnology Innovation Organization (BIO) Partnering platform.

To arrange a meeting with GRObio leadership, contact Tad Stewart, GRObios Chief Business Officer via email at tad.stewart@grobio.com.

About GRO Biosciences

GRO Biosciences (GRObio) is leveraging groundbreaking science to expand the amino acid alphabet and deliver on the promise of protein therapeutics. The Company is transforming treatments for increasingly prevalent chronic medical conditions including autoimmune and metabolic diseases to improve the lives of patients. GRObio is applying its platform to advance partnered and collaborative programs, as well as its own pipeline of protein therapeutics bearing unique NSAA (non-standard amino acid) chemistries. The Companys NSAA therapeutics feature previously unattainable capabilities including unprecedented duration of action and precise regulation of the immune system. GRObio, co-founded by Dr. George Church of Harvard Medical School in 2016, is headquartered in Cambridge, MA. Find GRObio on LinkedIn, Twitter, Instagram, Facebook and the web at grobio.com.

View source version on businesswire.com: https://www.businesswire.com/news/home/20211209005324/en/

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5 reasons why the GMO debate is over – Alliance for Science

Posted: December 10, 2021 at 2:35 am

Though we still hear some moaning and groaning about GMOs genetically modified organisms it primarily comes from a small and very vocal group. Most people simply arent concerned about GMOs as they focus on real and pressing issues, like the climate crisis and COVID-19 global pandemic. Even anti-GMO groups are turning their attention elsewhere as they redirect their conflict-driven business models to more lucrative topics, such as COVID conspiracy theories and peddling miracle cures. While the GMO debate has been percolating for nearly three decades, data indicate its now over. Here are five facts to support that conclusion.

Almost every scientific institution in the world recognizes the safety of genetically modified crops. Some 3,000 scientific studies have assessed the safety of these crops, in terms of human and environmental health, and 284 institutions globally recognize that GMO crops are safe. These include the Royal Society of Medicine, the American Medical Association, The World Academy of Sciences, the World Health Organization, the European Commission and the American Association for the Advancement of Science, among many others.

The most robust study was conducted by the National Academies of Science, which brought in experts from a wide range of food and agriculture disciplines to look at data compiled over the years. They all came to the same conclusion: No substantiated evidence of a difference in risks to human health between conventional and currently commercially available GM crops and no conclusive cause-and-effect evidence of environmental problems from GM crops.

As part of our work at the Alliance for Science, weve been using Cision media monitoring tools since 2018 to track the global conversation around GMOs. In 2020, we found that GMO visibility decreased by 26 percent from 2019 and the volume of social media posts on the topic decreased by 39 percent. Additionally, data show the average monthly favorability of the GMO conversation in both traditional and social media increased from 68 percent in 2019 to 78 percent in 2020. The shift was most pronounced in the free-for-all of social media, where favorability increased from just 60 percent in 2019 to 78 percent in 2020. Social media also saw a decrease in anti-GMO conspiratorial content in 2020, likely due to accounts that tend to promote such messages increasingly focusing on various COVID conspiracies. Meanwhile, top tier media like Reuters, CGTV, CNN and New Scientist replaced anti-GMO stalwarts, such as GM Watch and GMO-Free USA, as the top Twitter influencers on the topic in 2020. Journalists are increasingly reporting on GMOs in a positive or neutral tone that reflects the science and scientific consensus on safety.

Young people embrace technology in general as a tool for feeding the many while sparing the planet. Receptivity among this demographic is also improving as awareness grows about the role of GM crops in reducing agricultures environmental impact and greenhouse gas emissions associated with global warming. A recent unpublished survey by the Center for Food Integrity found that Gen Z and millennials tend to be more accepting of agricultural technology than their older counterparts and to see it as offering powerful solutions to humanitys problems.

Farmers around the world can see value in every harvest, as they achieve higher yields with less investment in fertilizers, pesticides and other inputs. This is true for both smallholder farmers and those with much larger operations. For example, smallholder farmers in Bangladesh cut their pesticide use by 62 percent and increased their profits six-fold by growing brinjal (eggplant) that has been genetically modified to resist the destructive fruit and shoot borer. Due to these benefits, biotechnology is the fastest-adopted crop technology in the world, increasing 112-fold from 1996 to 2019. Some 29 countries 56 percent of them developing nations grew 190.4 million hectares of GM crops in 2019.

Notably, GMO crop adoption is accelerating in South Asia and Africa. After years of debate, the Philippines this year approved the cultivation of Golden Rice and Bt eggplant is moving through the regulatory process. Nigeria, often called the Giant of Africa, has already approved insect-resistant GM cowpea and cotton. It is now moving to adopt drought-tolerant and insect-resistant maize (corn) and GM NEWEST rice that is water- and nitrogen-use efficient and tolerant of salty soils. Kenya, despite having a GMO moratorium in place, has adopted GM cotton and is expected to approve GM maize in 2022. This trend is likely to continue as African scientists are increasingly engaged in research that applies the tools of biotechnology to crops that are key to securing the livelihoods of smallholder farmers and supporting food security.

Brazil, whose agricultural sector is dominated by smallholder farmers, is emerging as another GM powerhouse. In addition to growing commodity crops like GM corn and soybean, Brazilian public sector researchers developed a GM pinto bean that resists a devasting plant disease. It is now being sold in the countrys grocery stores. Brazil this year also became the first country to approve the importation of flour made from GM wheat, giving a boost to a crop developed in neighboring Argentina, which has also embraced agricultural biotechnology. Its exciting to see government leaders put aside the politics and focus on what their nations and their farmers need.

Though consumers have been benefitting from GM crops without even realizing it, through higher yields that keep prices in check and reduced pesticide loads that make food healthier, nearly all the GM crops developed to date have catered to the needs of farmers. It is likely that consumers will similarly come to love GM crops as new products enter the market with traits that directly benefit them and/or reflect their values, such as enhanced nutrition, better taste and more sustainable approaches to agriculture.

Though Europeans are widely perceived as an anti-GMO stalwarts, concern about GMOs there dropped from 66 percent in 2010 to just 27 percent in 2019. That shift in sentiment is good news for countries that are influenced by European NGOs and policies that stand in the way of farmers accessing the benefits of GM crops.

The use of biotechnology to develop effective and safe COVID-19 vaccines has had a halo effect on GMO crops, improving public awareness about the technology and its benefits in both health and agricultural applications. Similarly, the advent of new tools like CRISPR and synthetic biology, which hold great promise for making agriculture more sustainable and producing food products with consumer benefits, are likely to reinforce the positive trends. Indeed, our media monitoring is already showing the conversation around gene editing is even more favorable than the one about GMOs, in both social and traditional media.

While its heartening to see the GMO debate dwindle, much time and momentum has been lost to addressing the opposition. Just 13 GM crops are currently on the market globally, most of them international commodity crops that support industry and livestock production. Only five cowpea, papaya, brinjal, pinto beans and Golden Rice are niche crops and food staples. This travesty is due primarily to misinformation (fear mongering) spread by GM opponents and the regulatory roadblocks they champion that make it difficult and expensive for public sector scientists and start-ups to develop crops with the traits that are useful to the people in their societies.

The GMO debate, driven largely by ill-informed or idle opposition from the well-fed West, is over. In a world wracked by a mutating virus and rising temperatures, action and answers matter more than opinions and rhetoric. The conversation we need to have now is about broadening access to the tools of biotechnology. Simply put, farmers need greater access to improved seeds and young scientists need more access to innovative tools.

It is estimated that agriculture will need to increase production by 70 percent to feed the worlds 9 billion citizens by 2050. And it needs to do this while greatly curbing its current impacts. Agriculture currently accounts for 50 percent of all global topsoil loss, 33 percent of the worlds GHG emissions, 75 percent of the nitrogen emissions and 80 percent of the deforestation worldwide. Biotechnology offers hope for shrinking agricultures footprint while producing more and better food. Lets stop the chatter and use todays tools to save the planet tomorrow.

Image: A smallholder farmer in Bangladesh shows off his harvest of GM brinjal. Photo: Alliance for Science

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Iterion Therapeutics Announces Initiation of Phase 1 Clinical Trial to Study Tegavivint in Combination with Osimertinib in Epidermal Growth Factor…

Posted: December 10, 2021 at 2:35 am

HOUSTON, Dec. 9, 2021 /PRNewswire/ --Iterion Therapeutics, Inc., a venture-backed, clinical-stage biotechnology company developing novel cancer therapeutics, today announced the initiation of a Phase 1 clinical trial to investigate tegavivint in a first-line combination study with osimertinib in previously untreated patients with metastatic epidermal growth factor receptor (EGFR)-positive Non-Small Cell Lung Cancer (NSCLC). Tegavivint is a potent and selective first-in-class small molecule inhibitor of Transducin beta-like Protein One (TBL1), a novel downstream target in the Wnt/beta-catenin signaling pathway. The trial (NCT04780568) is sponsored by The Ohio State University Comprehensive Cancer Center - Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC - James), and led by Regan M. Memmott, M.D., Ph.D., an OSUCCC James oncologist.

An important clinical challenge with EGFR-TKIs (tyrosine kinase inhibitors), including osimertinib, is that while such drugs are recommended as first line therapy in metastatic EGFR-positive NSCLC, this class of drugs enriches for "drug-tolerant persister cells" (DPCs), resulting in the eventual development of resistance. Researchers at OSUCCC - James determined that enrichment of DPC's by osimertinib is driven by activation of beta-catenin, and further demonstrated that administration of tegavivint in combination with osimertinib prevented osimertinib-induced enrichment of DPCs. Use of this combination also showed deeper anti-tumor responses and prolonged overall survival in mouse models of EGFR-mutant NSCLC.1

"For the estimated 15-30% of patients in the U.S. who have EGFR-positive NSCLC, treatment with EGFR-TKIs, such as osimertinib, has been shown to be very effective, but unfortunately patients will relapse as a result of their tumors eventually developing resistance," said Dr. Memmott, principal investigator for the study. "Research conducted at OSUCCC James suggests that combining tegavivint with osimertinib could curtail the osimertinib-induced drug-tolerant persister cells from developing due to tegavivint's ability to act as a beta-catenin inhibitor via TBL1 inhibition. This new Phase 1 clinical trial evaluates osimertinib in combination with tegavivint as a potential first-line treatment for EGFR-positive NSCLC, which is exciting in a disease that is the No. 1 cause of cancer-related death in the United States."

"We are excited to collaborate with OSUCCC and the National Cancer Institute to initiate this Phase 1 first-line study of tegavivint in combination with osimertinib in previously untreated patients with metastatic EGFR-mutant NSCLC," said Rahul Aras, Ph.D., CEO of Iterion. "NSCLC is the most common type of lung cancer, accounting for 85% of all lung cancer diagnoses, according to the American Society of Clinical Oncology (ASCO). This trial has the potential to help this enormous patient population and to further demonstrate tegavivint's unique mechanism of action of TBL1 inhibition, thereby disrupting the oncogenic activity of beta-catenin. Tegavivint has already demonstrated safety in desmoid tumor patients and is currently being investigated in additional clinical trials as a potential treatment for acute myeloid leukemia and solid and hematologic pediatric tumors."

This Phase 1 clinical trial is funded by Pelotonia, a Columbus-based organization that has raised more than $236 million for cancer research conducted at the OSUCCC James, and the V Foundation.

About Ohio State University Comprehensive Cancer Center - Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC - James)OSUCCC is one of 51 National Cancer Institute (NCI)-designated Comprehensive Cancer Centers and one of only a few centers funded by the NCI to conduct both Phase 1 and Phase 2 clinical trials on novel anticancer drugs sponsored by the NCI. The James at Brain and Spine Hospital has been ranked one of the top cancer hospitals in the nation by U.S. News & World Report and has achieved Magnet designation, the highest honor an organization can receive for quality patient care and professional nursing practice.

About Iterion TherapeuticsIterion Therapeutics is a venture-backed, clinical stage biotechnology company developing novel cancer therapeutics. The company's lead product, tegavivint, is a potent and selective small molecule that binds to TBL1 in the nucleus inhibiting nuclear beta-catenin signaling and oncogenic activity. Research demonstrating potent anti-tumor activity in a broad range of pre-clinical models indicate that tegavivint has the potential for clinical utility in multiple cancer types. Currently, tegavivint is the subject of three separate clinical trials: a Phase 1 clinical trial sponsored by MD Anderson Cancer Center in patients with relapsed or refractory acute myeloid leukemia (AML); a Phase 1/2 clinical trial sponsored by Children's Oncology Group Pediatric Early Phase Clinical Trials Network in pediatric patients with sarcomas, lymphomas and other solid tumors, excluding central nervous system (CNS) tumors; and a Phase 1 clinical trial sponsored by Ohio State University Comprehensive Cancer Center in EGRF-positive non-small cell lung cancer (NSCLC). Data from a prior Phase 1/2a clinical trial of tegavivint in patients with progressive desmoid tumors demonstrated safety and preliminary clinical efficacy. Iterion is the recipient of an up to$15.9 millionProduct Development Award from the Cancer Prevention and Research Institute ofTexas (CPRIT).For more information on Iterion, please visit https://iteriontherapeutics.com.

ContactTiberend Strategic Advisors, Inc. Jason Rando (Media)917-930-6346[emailprotected]

1Shankar Suman, Shu-Xiao Guan, Nastaran Navari, Rajeswara Rao Arasada, David P. Carbone and Regan M. Memmott DOI: 10.1158/1538-7445.AM2021-1110Published July 2021. Proceedings from the AACR Annual Meeting 2021

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Genetics research provides family the answer they’ve been searching years to discover – ABC15 Arizona

Posted: December 10, 2021 at 2:33 am

PHOENIX She may not be able to say much, but like any kid her age, her bright smile lights up even more when she thinks about Christmas.

You want to go see the Christmas lights on Friday?" asked sixth-grader Emmas mom Annette Medina.

Yeah, responded Emma with excitement.

Emma is just a ball of joy. Shes a happy little girl, everyone who meets Emma just falls in love with her, said Annette, sitting with her daughter at a park near their home.

At just 11 years old, Emma has spent more time in hospitals and doctors' offices than most will in their lives.

At about 6 months old, at regular standard pediatrician visits, we started noticing she was falling off the curve in growth, height, some of her developmental milestones, said Medina.

Born a healthy baby, the situation for Emma quickly turned. Soon after, she couldnt sit up without support. She wasnt crawling, walking, or talking.

We probably went on for about two and a half years of just seeing doctors and specialists and therapists, and everyone you can think of to figure out what was going on with her, said Medina.

Sadly, no one could provide an answer, which began to weigh on Medina who was filled with guilt.

There was so many days and nights that I had blamed myself, was there something I did in my pregnancy, was there anything we did wrong, was she exposed to something? said Medina.

They want to know will their child live a full life, and these types of questions are very difficult to answer if you dont know what the problem is, said Dr. Vinodh Narayanan.

Dr. Narayanan dedicates his life to providing families like Emmas with the answers that have long evaded them, leading the team of geneticists at TGen's Center for Rare Childhood Disorders.

They say the average time a family is searching for an answer is seven years before they come to us, said Dr. Narayanan.

He says the challenges posed by young patients at the center are among the most difficult in medicine, since families often arrive with just a collection of symptoms, looking for any clues about what is wrong with their children.

These cases are usually mysterious at first, but sequencing often allows us to provide these families with a diagnosis that can lead to therapies and a better life for their children, said Dr. Narayanan.

After hearing about the center on the news, Emma and her family had their genes sequenced and closely examined. The tests and research eventually discovered a genetic variant and a diagnosis of cerebellar facial dental syndrome a condition only found in about 20 people worldwide.

Seeing that there were kids older than her that had this I was able to say to myself, 'OK shes going to be able to get to at least this age,' said Medina.

Theres no treatment at the moment but if this experience has taught them anything its to never give up hope.

Today, there may not be an answer, tomorrow there could be an answer, said Medina.

Click here for more information on the center or to get help for a loved one.

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Ohio sheep farmers focus on improved flock genetics at 2021 symposium – Farm and Dairy

Posted: December 10, 2021 at 2:33 am

WOOSTER, Ohio Isabel Richards, of Gibraltar Farm, in central New York, knows what shes looking for in her sheep herd good body condition, ewes that are good at raising their lambs with minimal help, parasite resistance, to an extent. Not all of the sheep born on her farm make the cut to stay.

But different farms might have different goals for their flocks, Richards said at the 2021 Buckeye Shepherds Symposium, Dec. 3-4, in Wooster, Ohio. She encouraged sheep farmers to focus on whatever traits they want to encourage on their farms.

The big thing is just to see what makes sense for you to select for, she said.

Speakers at the symposium focused on genetics and reproduction. Richards isnt afraid to cull ewes that dont fit her operation.

Our ewe lambs get tough love, she said.

Body condition score is one of the big factors she culls for. There are performance things that she looks for ewes that produce a good number of lambs for their size, ewes that are good at mothering but she also needs them to be able to maintain their body condition scores.

She also selects for growth, to some extent. In New York, hay is expensive. So, Richards tries to raise lambs that can grow to market weight before she has to start feeding hay in the winter.

Mike Stitzlein, who raises club lambs in Ashland, Ohio, considers things like temperament, as well, when he is working on improving his flocks genetics. And as someone who raises lambs for the show ring, hes noticed what the show ring wants isnt always whats best for the sheep industry as a whole.

What pushes club lamb is whats popular in the show ring whats popular in the show ring is just fads, sometimes, Stitzlein said.

But also essential to improving genetics and reproduction is record keeping.

You cant manage what you dont measure, said Brady Campbell, an assistant professor focused on small ruminant management with Ohio State University.

On her farm, Richards tracks things including birth weights, estimated breeding values, mothering ability for ewes, body condition scores, weights at 60 days and 120 days and fecal egg counts for her livestock. The estimated breeding values come from the National Sheep Improvement Program, an organization that offers a system for genetic selection to help sheep farmers improve their herds.

Those things take time, and can be expensive being part of the national program costs Richards about $1,200 per year. But the numbers help her compare how well individual animals, and the herd are doing.

We can measure all day long but we also need to understand that we shouldnt just collect data to collect data, if were not going to use it, Campbell said.

The Ohio Sheep Improvement Association recognized award winners and scholarship recipients at the symposium Dec. 4. The Charles Boyles Master Shepherd Award went to Roger and Jan Cox, of Morrow County.

Roger and Jan Cox raise Katahdin sheep. The Cox family has a long history of sheep farming Rogers father raised sheep, and his ancestors, from Scotland and Ireland, also raised sheep. Roger Cox got his start in sheep with registered Hampshires in 1958, and later shifted to more commercial sheep, getting his first Katahdins in 2005.

Weve been so blessed, Roger Cox said. We had an opportunity to work hard, manage well, and see things come together.

The Distinguished Service Awards went to Gary Wilson, of Jenera; Don Hawk, of Danville; Jordan Beck, of Wauseon; Lori Shroyer, of DeGraff; and Robert Hunter, of Pickerington, all of whom have served on the Ohio Sheep and Wool Program board. Mike Stitzlein, who retired as the president of the association in 2019, received the Presidents Award.

The Friend of the Sheep Industry Award went to Amy Hurst, who assists with keeping track of membership records, checkoff accounting, newsletters and more for the association.

Youth recognized included Rachel Berk and Jim Stickley, with the Ralph H. Grimshaw Memorial Scholarship; Brandon Zuercher, with the Dr. Jack Judy Memorial Scholarship; Chelsea Graham, with the High Family Memorial Scholarship; and Emma Peters, Linsey Eddy and Ian Johnson, with the OSIA LEAD Council Scholarship.

The association also recognized Zoe Parrott, of Northmor FFA, as the state and national FFA sheep production proficiency winner, and Olivia Rinesmith, as the Ohio Lamb and Wool Ambassador.

2021 Buckeye Shepherd's Symposium awards

Representatives of the American Lamb Board gave an update on the checkoff program. Because of the pandemic, said Don Hawk, of the American Lamb Board, the program shifted its strategy to focus less on fine dining, and more on retail and consumer education.

Through partnering with food blogs and getting lamb into new recipes, the program estimates it reached four million or more people in 2020. It is also helping fund several research projects, including one at Michigan State University that looks at the sheep industrys environmental impact.

At the state level, the Ohio Sheep Improvement Association came up with a new strategic plan this year. Three broad goals in the plan are to ensure and maintain effective management, better serve members in Ohio and to provide relevant programming for the Ohio sheep industry.

With strong markets for lamb and wool and a strong base of farmers in the state, the association believes it is well-poised for the future.

We probably have the greatest potential for growth, Hawk said, about the sheep industry east of the Mississippi River.

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Ohio sheep farmers focus on improved flock genetics at 2021 symposium - Farm and Dairy

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Ticked Tabby Cats and Their Genetic Bases Elucidated – JD Supra

Posted: December 10, 2021 at 2:33 am

The domestic cat has been the subject of much study, recently involving its genetic structure, genomic DNA sequence, and comparisons with other felines. The first such study was published in 2014, when an international effort led by Stephen J. O'Brien at the Oceanographic Center, Nova Southeastern University, Ft. Lauderdale, Florida reported the complete genomic sequencing of the domestic cat, Felix catus. The report, entitled "Annotated features of domestic cat Felis catusgenome," was published inGigaScience2014,3:13 (August 5, 2014) (see"Domestic Cat Genome Sequenced"). The study reported sequencing of a female Abyssinian cat named Cinnamon, a mixed-breed cat from Russian named Boris, and Sylvester, a wildcat ancestor of domestic cats. The report showed that domestic cats have retained "a highly conserved ancestral mammal genome organization" in comparison with ancestral cats (seeDriscollet al., 2007, "The near eastern origin of cat domestication,"Science317: 51923). Both species, F. catusandFelix silvestris, have 38 chromosomes, 18 pairs of autosomes, and two pairs of dimorphic gender-determining chromosomes. Details of the domestic cat genome structure included the presence of 217 loci of endogenous retrovirus-like elements (amounting to 55.7% of the entire genome, comprised of long interspersed elements (LINEs), short interspersed elements (SINEs), satellite DNA, retroviral long terminal repeats (LTRs) and "others"); 21,865 protein coding genes (open reading frames or ORFs), detected by comparison with eight mammalian genomes (from human, chimpanzee, macaque, dog, cow, horse, rat, and mouse); and a wealth of genetic variability in single nucleotide polymorphisms (SNPs), insertion/deletion events (indels); novel families of complex tandem repeat elements; and short terminal repeat (STR) loci.

Since that time more individual cat genomic sequences have been determined and assembled in the 99 Lives Cat Genome Consortium. These efforts resulted in a more comprehensive elucidation of the feline genome and insights into genetic bases for disease. A paper published in the Public Library of Science, entitled "A new domestic cat genome assembly based on long sequence reads empowers feline genomic medicine and identifies a novel gene for dwarfism,"PLoS Genetics 16(10): e1008926 on October 20, 2020, reported a revisit of the genomic sequence of Cinnamon, an Abyssinian breed domestic cat previously sequenced. Rather than focusing on one cat, this group* performed whole genome sequencing (WGS) of 54 domestic cats and aligned the sequences to detect single nucleotide variants (SNVs) and structural variants (SVs). As a consequence of these studies, sequences comprising the ~300,000 gaps in the annotated sequence reported to the Cinnamon Abyssinian were obtained, to produce a new reference cat genome denoted in relevant databases as Felis_catus_9.0. This genome comprised 2.84 gigabasepairs (Gb), of which only 1.8% (1.38 megabasepairs, Mb) was not assigned to a specific chromosomal location.

While such assessments of global genetic structure are informative, analysis of genes resulting in well-known phenotypes have been slower to arrive. One such study was published in March 2021 in Animal Genetics 52: 321-32, entitled "Mining the 99 Lives Cat Genome Sequencing Consortium database implicates genes and variants for the Ticked locus in domestic cats (Felis catus)." In this paper, scientists from the U.S. and Australia* reported the genetic basis of the Ticked tabby coat pattern, a phenotype whose genetics long have been used empirically by cat breeders. (Amathematically, the Consortium database contains genetic information from 195 individual cats.)

Three autosomal alleles at a single genetic locus in wild and domestic cats are understood to control the tabby coat pattern: Abyssinian (Ta, also known as "ticked"); mackerel (Tm, aka striped); and blotched (tb, aka classic, blotched) (where these allelic abbreviations follow the convention that capital letters indicate Mendelian dominant traits and lower-case letters are inherited as recessive genes); the blotched phenotype was designated as the "classic" tabby by Linnaeus in 1758. Various combinations of these alleles result in complicated coat patterns involving the legs, head/face, tail, and torso.

Failure of this understanding to explain cats that have spotted coats, like Egyptian mau and ocicat, induced further genetic analyses that uncovered at least three other loci involved in coat pattern; these include Tabby and Ticked, where the Tabby locus affects the mackerel and blotched patterns. Located on the cat A chromosome, the candidate gene encoded by this locus, laeverin (LVRN) or transmembrane aminopeptidase Q, Taqpep, encodes 'a membrane-bound metalloprotease and plays a regulatory role in extravillous trophoblast migration." The genetic bases for coat patterns involving the Tabby locus were found to be even more complex, involving genes in a pigment switching signaling pathway, and can have a phenotype having individual hairs in the coat pattern that alternates between melanin types that are seen illusorily to be brown.

The other locus, the Ticked locus, had been localized on the cat B1 chromosome but the gene residing at the locus had not been determined until this report. The famous Cinnamon had the ticked pattern and accordingly her DNA was used by these researchers in one strategy as having the "reference" allele and in another as having the "variant" allele in performing their search for the gene or genes at the Ticked locus. Of the 195 cats in the 99 Cat Consortium database, 80 had either solid or white coats and their ticked-tabby phenotype could not be determined (regardless of their underlying genotype). Among the cats whose genomic DNA was assessed were two obligate heterozygous ticked cats identical by descent for their ticked allele as they are parentoffspring bred from a ticked Somali"; three known Abyssinians, including Cinnamon; and three other cats showing the ticked phenotype.

The researchers used eight short tandem repeats that segregated with the Ticked phenotype as identified by genome scanning methods to find a 17 centoMorgan (cM) linked region on cat chromosome B1 for their analysis of candidate variants. Seven phenotype filters were applied (e.g., "eliminate intergenic, intronic and synonymous variants; (ii) consider the variant zygosity for the [whole genome sequencing entry for Cinnamon;" etc.) to identify increasingly rare variants in this region of the B1 chromosome; after filtering only one variant remained, located in the gene for Dickkopf Wnt Signaling Pathway Inhibitor 4 (DKK4). The protein encoded by this gene is known to be "a member of the dickkopf (Dkk) family of cysteine-rich secretory proteins that are antagonists of Wnt signaling pathways, involved in antero-posterior axial patterning, limb development, somitogenesis and eye formation." These researchers report finding a G>A transition mutation at position 188 of this gene, resulting in a Cys63Tyr amino acid sequence change in the encoded protein. The researchers also reported finding at lower frequency another transition mutation (C>T) in this gene, resulting in a change at amino acid 18 from Ala to Val. The position of these mutations is shown in the following Figure:

These researchers further report that protein structure modeling suggests that these mutations disrupt "a key disulfide bond" in a "cysteine-rich domain" in the first mutation or a signal peptide cleavage site in the Dkk protein in the second mutation. The resulting change in protein conformation for the first mutation is illustrated in the following Figure:

In either case the researchers conclude that disrupting the function of this protein (as the consequences of these mutations suggest) results in the observed ticked phenotype.

The authors recognize that the ticked phenotype is rare in outbred cats (and the observed allele frequency, wherein no other cats from the 195 cats in the database have this allele, is consistent with its rarity) and dominant, suppressing patterning and resulting in cats having no discernable coat pattern. But they also recognize the search for genes that influence coat pattern in cats is not concluded, stating:

Additional genotyping of the proposed variants, in a large cohort of phenotyped cats, as well as supportive functional data, would clarify the role of these variants in cat coat pattern development. The identified variants do not clarify the pathways leading to the production of the spotted coat phenotype in cats, suggesting that additional genes influence other tabby patterns in domestic cats. The allelic series for the Ticked locus is suggested as TiA = TiCK > Ti+, where the TiA allele represents the p.Cys63Tyr variant and the TiCK allele represents the p.Ala18Val variant.

* From the Department of Veterinary Medicine and Surgery, College of Veterinary Medicine, University of Missouri Columbia, Columbia, MO and the School of Health and Behavioural Sciences, University of the Sunshine Coast, Sippy Downs, Australia; the paper in an appendix credits the hundreds of researcher who have contributed to the 99 Live Cat Genome Consortium.

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Ticked Tabby Cats and Their Genetic Bases Elucidated - JD Supra

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