STK26

While the space is just beginning to emerge, therapies for long-haul COVID-19 patients are still very much an unmet need. It’s the chronic disease that will likely define the first half of this decade – and it’s already all too familiar to many COVID-19 survivors. While the space is just beginning to emerge, therapies for long-haul COVID-19 patients are still very much an unmet need. So first, what exactly is a COVID-19 long-hauler? “If you look at the CDC’s website, it says that if you have a mild case of COVID-19 you could expect to recover in about two weeks. So, it starts to tell us that if people are taking longer than two weeks to feel better, they’re starting to get into that long-haulers zone. From what I’ve seen is, most of the people that I’m collecting data on, they’ve been sick for actually many, many months,” said Dr. Natalie Lambert , Ph.D., an associate research professor in biostatistics at the Indiana University School of Medicine, on a recent episode of Rooney Partners (RP) HealthCast. While there are a myriad of symptoms associated with the illness often referred to as long COVID, including brain fog and fatigue, a large number of the therapies currently in development are geared toward the lasting lung fibrosis and respiratory problems. Throughout the past couple of months, BioSpace has spoken with a number of companies dipping their toes into these waters, including Organicell Regenerative Medicine Inc , PureTech Health Plc ., CytoDyn Inc . and Bionano Genomics . PureTech Targets Lymphatic Flow Disorders – Including Long COVID On December 3, PureTech, a clinical-stage biotherapeutics company nestled in the Cambridge-Boston biotech hub, announced the commencement of a global Phase II trial evaluating its lead product candidate, LYT-100, in Long COVID respiratory complications and related sequelae. LYT-100 is an anti-fibrotic and anti-inflammatory oral small molecule intended to treat illnesses involving inflammation and fibrosis, and disorders of lymphatic flow such as idiopathic pulmonary fibrosis (IPF) and lymphedema. “We believe that the respiratory complications of long COVID are being driven by residual inflammation and fibrosis, or scarring, in the lungs. So we believe that the dual mechanism, anti-inflammatory and anti-fibrotic, is ideally suited to address the issues in long COVID respiratory complications,” said PureTech Head of Innovation, Dr. Michael C. Chen. “We see this as a major unmet need, and that includes the respiratory complications component of long COVID. So far, these respiratory complications are among the most common symptoms or problems that long-haulers are experiencing.” The trial is ongoing in the U.S. and Europe, and Chen told BioSpace that PureTech expects results in the second half of 2021. Organicell Sees Early Signs of Success in Long COVID With Zofin Miami, Florida-based Organicell, a clinical-stage biopharmaceutical company focused on harnessing the power of nanoparticles for the treatment of degenerative diseases, is awaiting a decision from the FDA regarding an Investigational New Drug (IND) application for a clinical trial of its proprietary therapeutic Zofin™ in COVID long-haulers. “We had an important call with FDA mid-January and now again have submitted and waiting for their final approval. Long Hauler population is so new and finally, FDA has set their framework in place for this population,” said Organicell Chief Science Officer Dr. Mari Mitrani. Zofin is an acellular biologic therapeutic derived from perinatal sources, consisting of 300 growth factors, cytokines and chemokines, along with other extracellular vesicles/nanoparticles derived from perinatal tissues. Organicell is in the midst of a placebo-controlled, randomized multi-center Phase I/II trial investigating Zofin for the treatment of moderate to severe acute respiratory syndrome (SARS) related to current COVID-19. The company has also had success with Zofin in treating four long-hauler patients under emergency INDs. Mitrani described the case of one of these patients, a previously healthy surgeon and marathon runner who had been in and out of the ICU for seven weeks with COVID-19. He was treated with three doses of Zofin, which is the standard regimen. “Between the second and the third infusion, he already saw changes in his shortness of breath, fatigue, and muscle aches that he was experiencing, and he was ready to go back to work after 3-4 weeks. He went from totally debilitated to going back to the OR,” Mitrani said. “We understand that this is a single case. We have done four of those single cases and have seen the same results, where patients go back to having less shortness of breath, less muscle aches, less fatigue. That is what drove us to actually an IND.” CytoDyn Calms Cytokine Storm With Leronlimab CytoDyn, a late-stage biotech based in Vancouver, WA, is going up against the cytokine storm responsible for the severity of many COVID-19 symptoms with its lead drug candidate, Vyrologix™ (leronlimab), a monoclonal antibody. Leronlimab, a viral-entry inhibitor against the CCR5 receptor, was originally intended as an HIV drug. It has shown promise in normalizing the immune response that has gone overboard in severely ill patients. Current data shows a trend toward immune function restoration by day seven of treatment with leronlimab, crucial to preventing opportunistic lung infections that could linger. “We believe the build-up of pro-inflammatory cytokines within the central nervous system leads to neuroinflammation. Neuroinflammation can affect the hypothalamus, leading to autonomic dysfunction such as high fevers, abnormalities of the sleep/wake cycle, cognitive abnormalities, and severe fatigue. We believe this mechanism of action is very similar to other post-viral syndromes,” CytoDyn Chief Medical Officer and Chairman of the Board, Dr. Scott Kelly told BioSpace. “Leronlimab is a CCR5 antagonist that can potentially help mitigate the neuroinflammatory process. Prior animal studies in macaques have shown that leronlimab crosses the blood-brain barrier with approximately 70-75% CCR5 receptor occupancy in the brain,” Kelly said. “If leronlimab can help alleviate the neuroinflammation, we believe it can significantly improve the quality of life of those affected with COVID Long-Haulers syndrome.” Leronlimab is currently undergoing a Phase II trial to evaluate its efficacy and safety for patients with prolonged symptoms caused by COVID-19. CytoDyn expects to complete the study by the end of July 2021. An Ounce of Prevention is Worth a Pound of Cure San Diego-based Bionano Genomics has an optical genome mapping instrument that can detect structural variations responsible for certain cancers and other developmental disorders. It could also tell us why some COVID-19 patients get sicker than others, and why some individuals’ symptoms linger. In January, Bionano announced that its diagnostic assay Saphyr was able to detect structural variants in individuals that may make them susceptible to severe COVID-19 disease. In a study conducted by Dr. Ravindra Kohle, Vice-Chairman of Pathology at the Medical College of Georgia, Augusta University and founder of the COVID-19 Host Genome SV Consortium, Saphyr was used to analyze the genomes of 37 severely ill, ICU-admitted COVID-19 patients. Against a healthy control group, 11 structural variants (SV) were identified involving 38 genes connected to three key host-viral interaction pathways: innate immunity and inflammatory response, airway resistance to pathogens, and viral replication, spread, and RNA editing. Duplication of one unique SV ,STK26 , which was not present in the control group, corroborated with data showing upregulation of this gene in severely ill patients. “Within that group of variants, there was one, in particular, that was seen in a handful of patients. This one made a lot of sense because it was actually a so-called duplication, where one piece of DNA appears twice,” said Bionano chief executive officer, Erik Holmlin.“The thinking is that there are factors in the immune systems of these patients [long haulers] that cause them to really remain off-regulated. This idea of upregulation is that, when we talked about duplication, that’s an example of up-regulation by a factor of two. So upregulation can be something that is driven at the genome level.” Holmlin explained that the discovery of these genomic variations using Saphyr could lead to the maximizing of resources during the pandemic, as well as more appropriate treatment that could prevent long-haul symptoms down the road. “If it were possible to stratify those patients as being ones who are highly likely to develop very severe illness and need interventions such as ventilators and other things that were relatively in short supply, that would be incredibly important information,” he said. “If you had that particular variant that we’re talking about here, it’s an indicator of a poor prognosis, but it can be used to get you the treatment that you need, and also used to rule out the need for that kind of treatment for other patients.”

COVID-19 Host Genome Structural Variant (SV) Consortium used Saphyr to identify SVs in severe COVID-19 patients that affect genes involved in immunity, airway mucous, and viral replication SVs found by several investigators point to a central role for disease severity of the interferon response pathway Consortium has added investigators from Augusta University, Boston Children’s Hospital, New York Genome Center, Radboud University, Rockefeller University, UC San Diego, Virginia Commonwealth University, and two dozen other institutes from around the world SAN DIEGO, Jan. 18, 2021 (GLOBE NEWSWIRE) -- Bionano Genomics, Inc. (Nasdaq: BNGO) announced that the last day of its five-day Next-Generation Cytogenomics Symposium featured presentations by members of the COVID-19 Host Genome Structural Variant (SV) Consortium using the Saphyr® system for optical genome mapping (OGM) to analyze the genomes of patients with severe COVID-19 disease. The presentations by scientists and clinicians from leading hospitals and research institutions in Europe and the US showed that Saphyr was able to detect structural variants that may predispose to severe or mild COVID-19 disease, which had not been identified previously by large studies using next-generation sequencing (NGS) or array-based methods to analyze genomic variation. Dr. Alex Hoischen, Radboud University, discussed his published results on genomic variants found in families with severe COVID-19. In two families with severely ill brothers, mutations were found in the Toll Like Receptor 7 gene (TLR7), which affects the production of interferons, signaling molecules used to control the immune response. Several other studies have since made similar findings in other genes of the TLR family. Dr. Hoischen discussed how individual patients each may carry individually rare variants, that are collectively common and point to important pathways involved in the disease. His interest in the consortium is based on his understanding that larger SVs have a greater chance to be rare and disruptive, and genome-wide studies have lacked so far in their assessment. Dr. Erich Jarvis, Howard Hughes Medical Institute investigator, professor at The Rockefeller University and head of the Vertebrate Genome Project (VGP), discussed an interesting difference between hospitalized patients and controls where the severely ill show more variation in a part of the Interferon Alpha and Beta Receptor Subunit 1 gene, a key part of the interferon pathway that regulates immune response. Dr. Jarvis is using Saphyr and the pipeline he developed for the VGP to build reference-quality genomes of patients and controls and will compare them with each other and with animal species that are sensitive to infection with SARS-CoV-2 or not, as previously reported. Dr. Ravindra Kolhe, Vice-Chairman of Pathology at the Medical College of Georgia at Augusta University and founder of the COVID-19 Host Genome SV Consortium explained that he founded the consortium because COVID-19 shows a split mortality where a very large number of people get infected, but only a small percentage of those get sick or die. Mortalities are associated with diabetes, hypertension and a history of heart failure, yet independent of that a seemingly random group of patients get extremely ill. Since other studies looking at host genetics use NGS or single nucleotide polymorphism (SNP) arrays that are ill suited to analyze SVs, the consortium focuses on the use of OGM to detect the larger genomic variants most likely to make the largest impact. Dr. Kolhe presented the previously announced finding from the consortium on 37 ICU-admitted, severely ill COVID-19 patients whose genomes were analyzed using Saphyr. In several severely ill patients Saphyr detected structural variants affecting important immune genes. In another patient Saphyr found a duplication of the STK26 gene, which reduces the production of interferon likely leading to reduced viral clearance and increasing the disease severity. When other severely ill patients were compared with asymptomatic COVID-19 patients, the same STK26 gene was found to be significantly more active in all the sick patients, making it a possible biomarker for disease severity. OGM identified many more variants in the severely ill patients affecting genes controlling immunity, airway mucous, and viral replication. Dr. Kolhe stated that his team wants to use structural variants identified with Saphyr to design preventative measures for those people whose genomes show them to be the most vulnerable and develop a biomarker panel that can be run at the time of patient admission, to make sure that appropriate measures are taken based on the genetic makeup and patients get the treatment they need as early as possible. In order to do so, the consortium has announced plans to analyze 1000 genomes with Saphyr allowing them to determine with high confidence which SV are involved in disease susceptibility and severity. Siavash Raisi, Dr. Vineet Bafna’s laboratory at UCSD presented on FaNDOM, an algorithm they developed that is used by the consortium to quickly and efficiently verify the structural variants identified by the Saphyr system. It was able to provide an independent confirmation of all of the variants identified by Saphyr using Bionano Access and Solve software and reported in the consortium publication. Dr. Silviu-Alin Bacanu, Virginia Commonwealth University described how existing resources and other host genome studies can be used to prioritize genes and structural variants identified with Saphyr. He described several studies including the genome-wide association studies on COVID-19 host genetics and the UK Biobank which has collected genomic data on more than 250,000 individuals. Although these large studies are unable to identify important large variants directly, their data can help prioritize variants detected by OGM based on whether they affect genes or pathways which these larger studies have identified as possible correlated with disease severity and outcome. Dr. Alan Beggs and Dr. Catherine Brownstein, Boston Children’s Hospital (BCH) discussed their previously announced study on the genomes of patients with Multisystem Inflammatory Syndrome in Children (MIS-C), a severe inflammatory attack of multiple organs weeks after COVID-19 infection in children with an average age of 8 years old. BCH has reported 67 cases of hospitalized MIS-C, and the Children’s Rare Disease Cohort Initiative has banked their specimens. Drs. Beggs and Brownstein are enrolling 50 patients each with MIS-C, severe COVID-19, and asymptomatic or mildly affected patients and will compare their genomes using OGM with Saphyr and with NGS. Dr. Michael Zody, New York Genome Center (NYGC) presented on the use of NGS on patients also analyzed with Saphyr. The NYGC has an active research project to sequence both the viral and the patient genomes using NGS. Their study is focused on patients with severe COVID-19 without prior high-risk diseases and on MIS-C cases, and in a collaboration with Dr. Jean-Laurent Casanova has found rare defects in immunity that affect the disease severity by altering the interferon response in patients. By combining the NGS data collected by NYGC with the OGM data from the consortium, smaller events and single nucleotide variants detected by NGS and large variants detected by Saphyr can be analyzed together. Recordings of all the presentations from the symposium can be found at About Bionano Genomics Bionano is a genome analysis company providing tools and services based on its Saphyr system to scientists and clinicians conducting genetic research and patient testing and providing diagnostic testing for those with autism spectrum disorder (ASD) and other neurodevelopmental disabilities through its Lineagen business. Bionano’s Saphyr system is a research use only platform for ultra-sensitive and ultra-specific structural variation detection that enables researchers and clinicians to accelerate the search for new diagnostics and therapeutic targets and to streamline the study of changes in chromosomes, which is known as cytogenetics. The Saphyr system is comprised of an instrument, chip consumables, reagents and a suite of data analysis tools, and genome analysis services to provide access to data generated by the Saphyr system for researchers who prefer not to adopt the Saphyr system in their labs. Lineagen has been providing genetic testing services to families and their healthcare providers for over nine years and has performed over 65,000 tests for those with neurodevelopmental concerns. For more information, visit or . Forward-Looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Words such as “may,” “will,” “expect,” “plan,” “anticipate,” “estimate,” “intend” and similar expressions (as well as other words or expressions referencing future events, conditions or circumstances) convey uncertainty of future events or outcomes and are intended to identify these forward-looking statements. Forward-looking statements include statements regarding our intentions, beliefs, projections, outlook, analyses or current expectations concerning, among other things: the timing and content of the presentations identified in this press release; the effectiveness and utility of Bionano’s technology in basic genetic research and clinical settings, and in the contexts and applications contemplated by the presentations identified in this press release; adoption of Saphyr as a standard platform in research and pathology settings; and the execution of Bionano’s strategy. Each of these forward-looking statements involves risks and uncertainties. Actual results or developments may differ materially from those projected or implied in these forward-looking statements. Factors that may cause such a difference include the risks and uncertainties associated with: the impact of the COVID-19 pandemic on our business and the global economy; general market conditions; changes in the competitive landscape and the introduction of competitive products; changes in our strategic and commercial plans; our ability to obtain sufficient financing to fund our strategic plans and commercialization efforts; the ability of medical and research institutions to obtain funding to support adoption or continued use of our technologies; the loss of key members of management and our commercial team; and the risks and uncertainties associated with our business and financial condition in general, including the risks and uncertainties described in our filings with the Securities and Exchange Commission, including, without limitation, our Annual Report on Form 10-K for the year ended December 31, 2019 and in other filings subsequently made by us with the Securities and Exchange Commission. All forward-looking statements contained in this press release speak only as of the date on which they were made and are based on management's assumptions and estimates as of such date. We do not undertake any obligation to publicly update any forward-looking statements, whether as a result of the receipt of new information, the occurrence of future events or otherwise. CONTACTS Company Contact: Erik Holmlin, CEO Bionano Genomics, Inc. +1 (858) 888-7610 eholmlin@bionanogenomics.com Investor Relations Contact: Ashley R. Robinson LifeSci Advisors, LLC +1 (617) 430-7577 arr@lifesciadvisors.com