Category Archives: Cell Medicine

Press Release

6 May 2020

Immunicum AB (publ) Receives Regenerative Medicine Advanced Therapy Designation from FDA for Ilixadencel in Kidney Cancer

Immunicum AB (publ; IMMU.ST) announced today that it has received Regenerative Medicine Advanced Therapy (RMAT) designation from the U.S. Food and Drug Administration (FDA) for the Companys lead candidate, ilixadencel, a cell-based, off-the-shelf immune primer for the treatment of metastatic Renal Cell Carcinoma (mRCC). The FDAs decision was made based on the previously communicated results from the Phase II MERECA clinical trial that evaluated the safety and efficacy of ilixadencel in combination with Sutent (sunitinib) in patients with newly diagnosed mRCC. Advantages of the RMAT designation include all the benefits of the Fast Track and Breakthrough Therapy Designation programs including guidance and early interactions with the FDA to discuss potential surrogate or intermediate endpoints to support accelerated approval as well as potential ways to satisfy post-approval requirements.

We are very excited to have received the RMAT designation for ilixadencel in kidney cancer as it recognizes both the potential of our novel therapeutic approach as well as the clear need for viable therapies to address this difficult-to treat disease. As a designation similar to the FDAs Breakthrough Therapy Designation, we will now also have the opportunity to receive direct guidance from the FDA which will inform key development decisions and ultimately bring us closer to delivering ilixadencel to patients in need, commented Alex Karlsson-Parra, CEO of Immunicum.

Established in 2017 under the 21st Century Cures Act in the United States, RMAT designation is an expedited program designed to facilitate the development and review of regenerative medicine therapies intended to address an unmet medical need in patients with serious conditions. An investigational regenerative medicine therapy (e.g. cell or gene therapy) is eligible for RMAT designation if it is intended to treat, modify, reverse or cure a serious condition and preliminary clinical evidence indicates that the drug or therapy has the potential to address unmet medical needs for such a disease or condition. As a cell therapy medicinal product, ilixadencel falls within the definition of a regenerative medicine therapy.

The latest results of the Phase II MERECA trial were presented in February at the ASCO-SITC Clinical Immuno-Oncology Symposium 2020 in Orlando, Florida. As of December 2019, the patient follow up data indicates a separation in Kaplan-Meier survival curves in favor of the ilixadencel treatment group in line with the projected separation based on the data from July 2019. The median OS value could not be calculated yet in either group as the data is not mature. The confirmed ORR for the ilixadencel treatment group was 42.2% (19/45) versus 24.0% (6/25) for the sunitinib control group.

Refer to the following link for more information on Regenerative Medicine Advanced Therapy Designation: https://bit.ly/3c7bFah

About MERECAMERECA is an exploratory, international, randomized, controlled and open-label Phase II clinical trial in which a total of 88 newly diagnosed, intermediate and poor-prognosis metastatic renal cancer patients were enrolled. Based on a 2-to-1 randomization, patients received either two intratumoral doses of ilixadencel before nephrectomy (surgical removal of the tumor-affected kidney) and subsequent treatment with sunitinib or sunitinib therapy alone post-nephrectomy. The primary objectives of the study are to evaluate median OS and 18-month survival rates. Secondary objectives include evaluation of safety and tolerability, tumor response and immunological profiling including T cell infiltration.

About renal cell cancer / carcinomaThere are approximately 273,000 new cases of Renal Cell Cancer diagnosed worldwide each year, representing approximately two percent of all cancers. The therapeutic effect of existing treatments, called targeted therapies, is often of short duration, with limited survival gain. With no alternatives to these therapies, there exists a relatively large unsatisfied medical need for new treatments that are effective, more cost-efficient and have less unwanted side effects.

About ilixadencelIlixadencel is an off-the-shelf cell-based cancer immunotherapy developed for the treatment of solid tumors. Its active ingredient is activated allogeneic dendritic cells, derived from healthy blood donors. Injection of these cells in the patients tumor generates an inflammatory response which in turns leads to tumor-specific activation of the patients cytotoxic T cells. To-date ilixadencel has been tested in a range of clinical trials in various solid tumor indications including metastatic Renal Cell Carcinoma (mRCC), hepatocellular carcinoma (HCC) and gastrointestinal stromal tumors (GIST) and in combination with several standard-of-care cancer therapies such as the tyrosine kinase inhibitors Sutent (sunitinib) and Stivarga (regorafenib), and the checkpoint inhibitor Keytruda (pembrolizumab). Ilixadencel has consistently maintained a positive safety and tolerability profile and demonstrated initial signs of efficacy as seen in the randomized Phase II MERECA trial. Ilixadencel is currently moving towards late-stage clinical development.

The information is such information that Immunicum is obliged to make public pursuant to EU Market Abuse Regulation. The information was released for public disclosure through the contact persons detailed below on 6 May 2020 at 8:00 am CET.

For more information, please contact:

Alex Karlsson-Parra, CSO and Interim CEO, ImmunicumTelephone: +46 8 732 8400E-mail: info@immunicum.com

Sijme Zeilemaker, COO, ImmunicumTelephone: +46 8 732 8400E-mail: info@immunicum.com

Read more here:
Immunicum AB (publ) Receives Regenerative Medicine Advanced Therapy Designation from FDA for Ilixadencel in Kidney Cancer - GlobeNewswire

The novel coronavirus causing COVID-19 seems to hit some people harder than others, with some people experiencing only mild symptoms and others being hospitalized and requiring ventilation. Though scientists at first thought age was the dominant factor, with young people avoiding the worst outcomes, new research has revealed a suite of features impacting disease severity. These influences could explain why some perfectly healthy 20-year-old with the disease is in dire straits, while an older 70-year-old dodges the need for critical interventions.

These risk factors include:AgeDiabetes (type 1 and type 2)Heart disease and hypertensionSmokingBlood typeObesityGenetic factors

About 8 out of 10 deaths associated with COVID-19 in the U.S. have occurred in adults ages 65 and older, according to the U.S. Centers for Disease Control and Prevention (CDC). The risk of dying from the infection, and the likelihood of requiring hospitalization or intensive medical care, increases significantly with age. For instance, adults ages 65-84 make up an estimated 4-11% of COVID-19 deaths in the U.S, while adults ages 85 and above make up 10-27%.

The trend may be due, in part, to the fact that many elderly people have chronic medical conditions, such as heart disease and diabetes, that can exacerbate the symptoms of COVID-19, according to the CDC. The ability of the immune system to fight off pathogens also declines with age, leaving elderly people vulnerable to severe viral infections, Stat News reported.

Related: Coronavirus in the US: Latest COVID-19 news and case counts

Diabetes mellitus a group of diseases that result in harmful high blood sugar levels also seems to be linked to risk of more severe COVID-19 infections.

The most common form in the U.S. is type 2 diabetes, which occurs when the body's cells don't respond to the hormone insulin. As a result, the sugar that would otherwise move from the bloodstream into cells to be used as energy just builds up in the bloodstream. (When the pancreas makes little to no insulin in the first place, the condition is called type 1 diabetes.)

In a review of 13 relevant studies, scientists found that people with diabetes were nearly 3.7 times more likely to have a critical case of COVID-19 or to die from the disease compared with COVID-19 patients without any underlying health conditions (including diabetes, hypertension, heart disease or respiratory disease), they reported online April 23 in the Journal of Infection.

Even so, scientists don't know whether diabetes is directly increasing severity or whether other health conditions that seem to tag along with diabetes, including cardiovascular and kidney conditions, are to blame.

That fits with what researchers have seen with other infections and diabetes. For instance, flu and pneumonia are more common and more serious in older individuals with type 2 diabetes, scientists reported online April 9 in the journal Diabetes Research and Clinical Practice. In a literature search of relevant studies looking at the link between COVID-19 and diabetes, the authors of that paper found a few possible mechanisms to explain why a person with diabetes might fare worse when infected with COVID-19. These mechanisms include: "Chronic inflammation, increased coagulation activity, immune response impairment and potential direct pancreatic damage by SARS-CoV-2."

Related: 13 coronavirus myths busted by science

Mounting research has shown the progression of type 2 diabetes is tied to changes in the body's immune system. This link could also play a role in poorer outcomes in a person with diabetes exposed to SARS-CoV-2, the virus that causes COVID-19.

No research has looked at this particular virus and immune response in patients with diabetes; however, in a study published in 2018 in the Journal of Diabetes Research, scientists found through a review of past research that patients with obesity or diabetes showed immune systems that were out of whack, with an impairment of white blood cells called Natural Killer (NK) cells and B cells, both of which help the body fight off infections. The research also showed that these patients had an increase in the production of inflammatory molecules called cytokines. When the immune system secretes too many cytokines,a so-called "cytokine storm" can erupt and damage the body's organs. Some research has suggested that cytokine storms may be responsible for causing serious complications in people with COVID-19, Live Science previously reported. Overall, type 2 diabetes has been linked with impairment of the very system in the body that helps to fight off infections like COVID-19 and could explain why a person with diabetes is at high risk for a severe infection.

Not all people with type 2 diabetes are at the same risk, though: A study published May 1 in the journal Cell Metabolism found that people with diabetes who keep their blood sugar levels in a tighter range were much less likely to have a severe disease course than those with more fluctuations in their blood sugar levels.

Scientists aren't sure whether this elevated risk of a severe COVID-19 infection also applies to people with type 1 diabetes (T1D). A study coordinated by T1D Exchange a nonprofit research organization focused on therapies for those with type 1 diabetes launched in April to study the outcomes of T1D patients infected with COVID-19. When a person with T1D gets an infection, their blood sugar levels tend to spike to dangerous levels and they can have a buildup of acid in the blood, something called diabetic ketoacidosis. As such, any infection can be dangerous for someone with type 1 diabetes.

People with conditions that affect the cardiovascular system, such as heart disease and hypertension, generally suffer worse complications from COVID-19 than those with no preexisting conditions, according to the American Heart Association. That said, historically healthy people can also suffer heart damage from the viral infection.

The first reported coronavirus death in the U.S., for instance, occurred when the virus somehow damaged a woman's heart muscle, eventually causing it to burst, Live Science reported. The 57-year-old maintained good health and exercised regularly before becoming infected, and she reportedly had a healthy heart of "normal size and weight." A study of COVID-19 patients in Wuhan, China, found that more than 1 in 5 patients developed heart damage some of the sampled patients had existing heart conditions, and some did not.

In seeing these patterns emerge, scientists developed several theories as to why COVID-19 might hurt both damaged hearts and healthy ones, according to a Live Science report.

In one scenario, by attacking the lungs directly, the virus might deplete the body's supply of oxygen to the point that the heart must work harder to pump oxygenated blood through the body. The virus might also attack the heart directly, as cardiac tissue contains angiotensin-converting enzyme 2 (ACE2) a molecule that the virus plugs into to infect cells. In some individuals, COVID-19 can also kickstart an overblown immune response known as a cytokine storm, wherein the body becomes severely inflamed and the heart could suffer damage as a result.

People who smoke cigarettes may be prone to severe COVID-19 infections, meaning they face a heightened risk of developing pneumonia, suffering organ damage and requiring breathing support. A study of more than 1,000 patients in China, published in the New England Journal of Medicine, illustrates this trend: 12.3% of current smokers included in the study were admitted to an ICU, were placed on a ventilator or died, as compared with 4.7% of nonsmokers.

Cigarette smoke might render the body vulnerable to the coronavirus in several ways, according to a recent Live Science report. At baseline, smokers may be vulnerable to catching viral infections because smoke exposure dampens the immune system over time, damages tissues of the respiratory tract and triggers chronic inflammation. Smoking is also associated with a multitude of medical conditions, such as emphysema and atherosclerosis, which could exacerbate the symptoms of COVID-19.

A recent study, posted March 31 to the preprint database bioRxiv, proposed a more speculative explanation as to why COVID-19 hits smokers harder. The preliminary research has not yet been peer-reviewed, but early interpretations of the data suggest that smoke exposure increases the number of ACE2 receptors in the lungs the receptor that SARS-CoV-2 plugs into to infect cells.

Many of the receptors appear on so-called goblet and club cells, which secrete a mucus-like fluid to protect respiratory tissues from pathogens, debris and toxins. It's well-established that these cells grow in number the longer a person smokes, but scientists don't know whether the subsequent boost in ACE2 receptors directly translates to worse COVID-19 symptoms. What's more, it's unknown whether high ACE2 levels are relatively unique to smokers, or common among people with chronic lung conditions.

Several early studies have suggested a link between obesity and more severe COVID-19 disease in people. One study, which analyzed a group of COVID-19 patients who were younger than the age of 60 in New York City, found that those who were obese were twice as likely as non-obese individuals to be hospitalized and were 1.8 times as likely to be admitted into critical care.

"This has important and practical implications" in a country like the U.S. where nearly 40% of adults are obese, the authors wrote in the study, which was accepted into the journal Clinical Infectious Diseases but not yet peer-reviewed or published. Similarly, another preliminary study that hasn't yet been peer-reviewed found that the two biggest risk factors for being hospitalized from the coronavirus are age and obesity. This study, published in medRxiv looked at data from thousands of COVID-19 patients in New York City, but studies from other cities around the world found similar results, as reported by The New York Times.

A preliminary study from Shenzhen, China, which also hasn't been peer-reviewed, found that obese COVID-19 patients were more than twice as likely to develop severe pneumonia as compared with patients who were normal weight, according to the report published as a preprint online in the journal The Lancet Infectious Diseases. Those who were overweight, but not obese, had an 86% higher risk of developing severe pneumonia than did people of "normal" weight, the authors reported. Another study, accepted into the journal Obesity and peer-reviewed, found that nearly half of 124 COVID-19 patients admitted to an intensive care unit in Lille, France, were obese.

It's not clear why obesity is linked to more hospitalizations and more severe COVID-19 disease, but there are several possibilities, the authors wrote in the study. Obesity is generally thought of as a risk factor for severe infection. For example, those who are obese had longer and more severe disease during the swine flu epidemic, the authors wrote. Obese patients might also have reduced lung capacity or increased inflammation in the body. A greater number of inflammatory molecules circulating in the body might cause harmful immune responses and lead to severe disease.

Blood type seems to be a predictor of how susceptible a person is to contracting SARS-CoV-2, though scientists haven't found a link between blood type per se and severity of disease.

Jiao Zhao, of The Southern University of Science and Technology, Shenzhen, and colleagues looked at blood types of 2,173 patients with COVID-19 in three hospitals in Wuhan, China, as well as blood types of more than 23,000 non-COVID-19 individuals in Wuhan and Shenzhen. They found that individuals with blood types in the A group (A-positive, A-negative and AB-positive, AB-negative) were at a higher risk of contracting the disease compared with non-A-group types. People with O blood types (O-negative and O-positive) had a lower risk of getting the infection compared with non-O blood types, the scientists wrote in the preprint database medRxiv on March 27; the study has yet to be reviewed by peers in the field.

In a more recent study of blood type and COVID-19, published online April 11 to medRxiv, scientists looked at 1,559 people tested for SARS-CoV-2 at New York Presbyterian hospital; of those, 682 tested positive. Individuals with A blood types (A-positive and A-negative) were 33% more likely to test positive than other blood types and both O-negative and O-positive blood types were less likely to test positive than other blood groups. (There's a 95% chance that the increase in risk ranges from 7% to 67% more likely.) Though only 68 individuals with an AB blood type were included, the results showed this group was also less likely than others to test positive for COVID-19.

The researchers considered associations between blood type and risk factors for COVID-19, including age, sex, whether a person was overweight, other underlying health conditions such as diabetes mellitus, hypertension, pulmonary diseases and cardiovascular diseases. Some of these factors are linked to blood type, they found, with a link between diabetes and B and A-negative blood types, between overweight status and O-positive blood groups, for instance, among others. When they accounted for these links, the researchers still found an association between blood type and COVID-19 susceptibility. When the researchers pooled their data with the research by Zhao and colleagues out of China, they found similar results as well as a significant drop in positive COVID-19 cases among blood type B individuals.

Why blood type might increase or decrease a person's risk of getting SARS-CoV-2 is not known. A person's blood type indicates what kind of certain antigens cover the surfaces of their blood cells; These antigens produce certain antibodies to help fight off a pathogen. Past research has suggested that at least in the SARS coronavirus (SARS-CoV), anti-A antibodies helped to inhibit the virus; that could be the same mechanism with SARS-CoV-2, helping blood group O individuals to keep out the virus, according to Zhao's team.

Many medical conditions can worsen the symptoms of COVID-19, but why do historically healthy people sometimes fall dangerously ill or die from the virus? Scientists suspect that certain genetic factors may leave some people especially susceptible to the disease, and many research groups aim to pinpoint exactly where those vulnerabilities lie in our genetic code.

In one scenario, the genes that instruct cells to build ACE2 receptors may differ between people who contract severe infections and those who hardly develop any symptoms at all, Science magazine reported. Alternatively, differences may lie in genes that help rally the immune system against invasive pathogens, according to a recent Live Science report.

For instance, a study published April 17 in the Journal of Virology suggests that specific combinations of human leukocyte antigen (HLA) genes, which train immune cells to recognize germs, may be protective against SARS-CoV-2, while other combinations leave the body open to attack. HLAs represent just one cog in our immune system machinery, though, so their relative influence over COVID-19 infection remains unclear. Additionally, the Journal of Virology study only used computer models to simulate HLA activity against the coronavirus; clinical and genetic data from COVID-19 patients would be needed to flesh out the role of HLAs in real-life immune responses.

Originally published on Live Science.

The rest is here:
Why COVID-19 kills some people and spares others. Here's what scientists are finding. - Livescience.com

As the rumblings of a pandemic began to be felt at the beginning of the year, scientists at Penn started work to develop a vaccine and assess possible treatments. But the scope of COVID-19 studies at the University goes much broader. Scientists whose typical work finds them investigating autoimmune disease, influenza, HIV/AIDS, Ebola, cancer, hemophilia, and more, are now applying their deep understanding of biology to confront a novel threat.

The more scientists and clinicians observe about the virus, the more avenues of investigation emerge, aiming to shed light on questions such as what happens once the virus enters the body, what treatments might be of benefit, and how society should take action to keep transmission low.

To dig into what scientists around campus are asking and learning, Penn Today spoke with several who have pivoted their research to focus on COVID-19. Their work, while in its early days, is in many cases already finding applications in the fight against this ferocious virus, and may well shape the next steps to defeat it.

Another respiratory infection, influenza, has been a focus of research led by Andrew Vaughan of the School of Veterinary Medicine. But Vaughan didnt hesitate to begin studies of the novel coronavirus once its eventual impact became apparent.

Its not a stretch for our lab, he says. All the projects in our lab focus on repair and regeneration of the lungs after injury. The majority of my studies are to some degree agnostic about what is causing the injury.

Earlier work by his group, for example, showed that a lung cell transplant could boost healing in mice affected by a severe bout with flu. Now, graduate students and research specialists in his labworking no more than two together at a time to maximize social distancingare conducting new experiments focused more specifically on the biology of SARS-CoV-2, alongside parallel efforts by Edward Morrissey from the Perelman School of Medicine (PSOM). Knowing that the Ace2 receptor on lung cells is the gateway for the virus into the human body, theyre genetically manipulating alveolar type-two lung cells, those that are particularly essential for continuing oxygen exchange deep in the lungs, to alter or block ACE2 gene expression to try to prevent viral entry.

These alveolar type-two cells seem to be particularly susceptible to injury in both influenza and perhaps even more so in COVID-19, says Vaughan. In a perfect world, you might be able to take these genetically edited type-two cells and use them as a cellular therapy. I dont know that this is going to happen in time to impact this pandemic, but even if the pathogen the next time around is slightly different, we may still be able to employ these types of regenerative responses to help the lung recover better from injury.

In a separate project, Vaughan is partnering with Penn Vets Montserrat Anguera to explore a curious feature of COVID-19 disease: the fact that more men than women become severely ill and die. A number of hypotheses have been put forward to explain the disparity, but the two labs are investigating one particular possibility.

Dr. Anguera had posted something on Twitter saying that the ACE2 gene happens to be on the X chromosome, meaning that women have two copies of it, says Vaughan. I immediately texted her and said, I think theres something to that.

Normally women inactivate one of their X chromosomes, but some genes can escape this inactivation. This means its possible women may have higher ACE2 expression than men. Somewhat counterintuitively, scientists have actually found that higher ACE2 levels actually reduce lung injury, even though ACE2 is also what the virus depends on to enter cells.

Hormone expression levels are, of course, another factor that may influence sex differences in disease. Together, Anguera and Vaughans groups are both studying ACE2 expression and exposing alveolar type-two cells to various hormones to see how expression of viral receptors, Ace2 and others, changes. Ultimately wed like to see if this changes susceptibility to infection, working with Susan Weiss and others, says Vaughan.

Individual differences in how people respond to infection may be influenced by their unique genomic sequences. Penn Integrates Knowledge Professor Sarah Tishkoff of PSOM and the School of Arts & Sciences, is probing the rich sources of genomic data her group already had in hand to look for patterns that could explain differences in disease susceptibility. As in Vaughan and Angueras work, ACE2 is a focus.

This gene is very important for general health, Tishkoff says. Women have two copies, men have one; it plays a role in regulating blood pressure; its in the kidneys; its in the gut. We want to understand the role that variation at this gene may play in risk for COVID-19, severity of disease in people with underlying health conditions, and differences in the prevalence of disease in men and women.

Using genomic data from 2,500 Africans collected for another project, Tishkoffs team is looking for patterns of genetic diversity. Early findings suggest that natural selection may have acted upon on version of the ACE2 gene, making it more common in some African populations with with high exposure to animal viruses.

Shes also collaborating with Anurag Vermaand Giorgio Sirugo of Penn Medicine to analyze genetic variation in samples from the Penn Medicine Biobank, looking in particular at people of African descent. Were seeing disturbing health disparities with COVID, with African Americans at higher risk for serious illness, says Tishkoff. This disparity mostlikelyhas to do with inequities in access to health care and socioeconomic factors, but were also looking to see if genomic variation may be playing a role.

Looking ahead, Tishkoff hopes to partner with Daniel Rader and others through the Center for Global Genomics and Health Equity to work with the West Philadelphia community. Wed like to do testing to understand the prevalence of infection and identify environmental and genetic risk factors for disease, she says.

The immune reaction to SARS-CoV-2 is a double-edged sword. The immune system is what eliminates the virus, says E. John Wherry of PSOM. The immune system is what we need to activate with a good vaccine. But also, especially in many respiratory infections, the immune system is what also causes damage. A healthy outcome means your immune system is striking a balance between killing off the virus and not doing so much damage that it kills you.

Wherry and PSOMs Michael Betts have embarked on a study to discern both the magnitude of patients immune responses as well as their flavor, that is, what components in the immune system are being activated by the coronavirus. Theyre doing so by working with clinicians at the Hospital of the University of Pennsylvania (HUP) and, soon, at Penn Presbyterian Medical Center, to collect blood samples from patients with severe and more mild infections, as well as patients who have recovered from illness, to profile their immune reactions.

Its one of the beautiful things about Penn. Everyone is working as a team, being selfless, being present, and bringing all their expertise to bear on this crisis. E. John Wherry, Perelman School of Medicine

We are observing a huge amount of heterogeneity across these patient samples, says Betts. But were also identifying some relatively unifying characteristics, indicating there are mechanisms that everyone uniformly uses to fight off this infection.

This variety across patients strongly suggests that the treatments that work for one patient may not for another, Wherry and Betts note. For that reason, they are speaking daily with their colleagues on the front lines of COVID-19 care, relaying what theyre finding out in the lab to adjust and personalize care in the clinic.

Its one of the beautiful things about Penn, says Wherry. Everyone is working as a team, being selfless, being present, and bringing all their expertise to bear on this crisis.

Plenty of recent scientific attention has been paid to the role of the gut microbiome in health. But the medical schools Ronald Collman and Frederic Bushman have been devoting attention to how the community of bacteria, viruses, fungi, and parasites that dwell in the respiratory tract affect health and disease risk. They are now addressing that question in the context of COVID-19.

There are two reasons were interested in studying this, Collman says. First is that the microbiome can help set the tone for the immune response to infections, influencing whether a patient ends up with mild or severe disease. And second, the microbiome is where infectious agents that can cause infection can arise from. So if a patient dies of an eventual pneumonia, the pathogen that caused that pneumonia may have been part of that individuals respiratory tract microbiome.

Working with nurses at HUP to collect samples, Collman and Bushman are analyzing the microbiome of both the upper (nose and throat) and lower (lung) portions of the respiratory tract of COVID-19 patients. These samples are being used by other groups, such as those developing diagnostic tests, while Collman and Bushmans labs work to identify the types and quantities of organisms that compose the microbiome to find patterns in how they correlate with disease.

Were hoping that if we can find that the response to the virus is different in people with different upper respiratory tract microbiomes, then we could manipulate the microbiome, using particular antibiotics, for example, to make it more likely that patients would have a mild form of the disease.

Absent a vaccine, researchers are looking to existing drugssome already approved by the U.S. Food and Drug Administration for other maladiesto help patients recover once infected. Throughout his career, Ronald Harty of Penn Vet has worked to develop antivirals for other infections, such as Ebola, Marburg, and Lassa Fever.

Our antivirals are sometime referred to as host-oriented inhibitors because theyre designed to target the interaction between host and viral proteins, says Harty. Though many of the biological details of how SARS-CoV-2 interacts with the human body are distinct from the other diseases Harty has studied, his group noticed a similarity: A sequence hes targeted in other virusesa motif called PPxYis also present in the spike protein of SARS-CoV-2, which the coronavirus uses to enter cells.

This caught our eye, says Harty, and piqued our interest in the very intriguing possibility that this PPxY motif could play a role in the severity of this particular virus.

Harty is testing antivirals he has helped identify that block the replication of Ebola, Marburg, and other viruses to see if they make a dent on the activity of SARS-CoV-2. Those experiments will be done in collaboration with colleagues whose labs can work in BSL-III or -IV laboratories, such as Penns Weiss.

Also of interest is the speculation that the coronavirus might disrupt cell-cell junctions in the human body, making them more permeable for virus spread. Hartys lab will be examining the potential interactions between the viral structural proteins and human proteins responsible for maintaining these cellular barriers.

Another faculty member is assessing whether a drug developed for a very different conditionin this case, pulmonary arterial hypertension (PAH)could serve coronavirus patients. Henry Daniell of the School of Dental Medicine recently shared news that a drug grown in a plant-based platform to boost levels of ACE2 and its protein product, angiotensin (1-7), was progressing to the clinic to treat PAH. Daniell is now working with Kenneth Margulies from Penn Medicine to explore whether this novel oral therapy can improve the clinical course of patients with symptomatic COVID-19 infection.

Reduced ACE2 expression has been linked to acute respiratory distress, severe lung injury, multi-organ failure and death, especially in older patients. The earlier preclinical studies in PAH animal models showed that orally delivered ACE2 made in plant cells accumulated ten times higher in the lungs than in the blood and safely treated PAH. Now, new clinical studies have been developed to explore whether oral supplementation of ACE2 and angiotensin-1-7 can help mitigate complications of COVID-19 disease. The fact that freeze-dried plant cells can be stored at room temperature for as long as a year and can be taken at home by COVID-19 patients make this novel approach an attractive potential option.

This trial has been given a high priority by the Penn Clinical Trial Working Group, says Daniell. Im pleased that this looks to be on the cusp of moving forward to help the growing number of COVID-19 patients.

As the coronavirus began to spread in the United States, biologist Joshua Plotkin of the School of Arts & Sciences began to raise alarms about Philadelphias St. Patricks Day parade, which had been scheduled to be held March 15, potentially drawing thousands to downtown streets. He had good reason to be concerned: His studies of the 1918 flu pandemic had explored disease incidence and spread, and it was hard to avoid noticing the role of the Liberty Loan parade down Broad Street in triggering a rampant spread of flu a century ago.

Now, with work conducted with two graduate students from Princeton University, Dylan Morris and Fernando Rossine, along with Princeton faculty member Simon Levin, Plotkin has mathematically sound advice for policymakers hoping to effectively stem the spread of a pandemic. In a preprint on arXiv.org, they share optimal, near-optimal, and robust strategies for how to time interventions such as social distancing.

This boils down to knowing what is the best way, of all the infinite possibilities, to intervene using public health measure, says Plotkin. Thats a problem we can solve with math, my colleagues Dylan and Fernando realized.

Their analysis makes the realistic assumption that policymakers can only enforce social distancing for a limited amount of time, and aims to minimize the peak incidence of disease. The optimal strategy, they found, is to start by introducing moderate social distancing measures to keep the incidence rate the same for a period of time. This would mean that every person with COVID-19 would infect one additional person. Then the intervention should switch over to a full suppressionthe strongest possible quarantinefor the rest of the period. At the end of that period, all restrictions would be lifted.

This works because you dont want to fully suppress disease spread right off the bat, says Plotkin, because then at the end, after you remove restrictions, there will be a second peak that is just as large as the first. By employing a moderate suppression at the beginning, youre building up a population of people who are going to recover and become immune, without letting the epidemic get out of control.

Unsurprisingly, timing is key. Attempting the optimal intervention would be disastrous, in practice, because of inevitable errors in timing. Intervening too early is pretty bad, because you get a bigger second peak, he says. But intervening too late is even worse. The key lesson is that a robust intervention is more important than an optimal one.

Plotkin and his colleagues are hoping to share the findings widely, including with local decision makers, to help them navigate a likely second wave of COVID-19.

Montserrat Anguera is an associate professor of biomedical sciences at the University of Pennsylvania School of Veterinary Medicine.

Michael Betts is a professor of microbiology at the University of Pennsylvania Perelman School of Medicine.

Frederic Bushman is the William Maul Measey Professor in Microbiology at the University of Pennsylvania Perelman School of Medicine.

Ronald Collman is a professor of Medicine at the University of Pennsylvania Perelman School of Medicine.

Henry Daniell is vice-chair and W.D. Miller Professor in the Department of Basic and Translational Sciences in the University of Pennsylvania School of Dental Medicine.

Ronald Harty is a professor of pathobiology and microbiology at the University of Pennsylvania School of Veterinary Medicine.

Kenneth Margulies is a professor of medicine and physiology and research and fellowship director of the Heart Failure and Transplant Program at the University of Pennsylvania Perelman School of Medicine.

Joshua Plotkin is the Walter H. and Leonore C. Annenberg Professor of the Natural Sciences in the Department of Biology at the University of Pennsylvania School of Arts & Sciences. He has secondary appointments in the Department of Mathematics and in the School of Engineering and Applied Sciences Department of Computer and Information Science.

Sarah Tishkoff is the David and Lyn Silfen University Professor with appointments in the Perelman School of Medicines Department of Genetics and the School of Arts and Sciences Department of Biology. A Penn Integrates Knowledge Professor, she is also director of the Penn Center for Global Genomics and Health Equity.

Andrew Vaughan is an assistant professor of biomedical sciences at the University of Pennsylvania School of Veterinary Medicine.

E. John Wherry is chair of the Department of Systems Pharmacology and Translational Therapeutics, director of the Institute for Immunology, and the Richard and Barbara Schiffrin Presidents Distinguished Professor at the University of Pennsylvania Perelman School of Medicine.

Homepage image: Researchers around the University are taking a variety of approaches to study the novel coronavirus (particles of which are shown in purple), informed by past expertise and newly formed collaborations. (Image: National Institutes of Health)

Go here to see the original:
Coming together to solve the many scientific mysteries of COVID-19 - Penn: Office of University Communications

Abstracts originally accepted for presentation at the 2020 American Thoracic Society (ATS) International Conference

Findings confirm that aTyrs lead clinical candidate, ATYR1923, selectively binds to Neuropilin-2 (NRP2), a unique target expressed on key immune cells in inflammatory conditions

SAN DIEGO, May 05, 2020 (GLOBE NEWSWIRE) -- aTyr Pharma Inc. Inc. (Nasdaq: LIFE), a biotherapeutics company engaged in the discovery and development of innovative medicines based on novel immunological pathways, today announced that two abstracts originally accepted for presentation at the 2020 ATS International Conference will be published in the ATS journal, American Journal of Respiratory and Critical Care Medicine. One abstract characterizes the molecular basis for ATYR1923s immunomodulatory properties, including its ability to specifically and selectively bind to NRP2, a target that has been implicated in a broad range of immune-mediated diseases. The second abstract demonstrates that NRP2 is expressed on key immune cells in inflammatory conditions, including sarcoidosis granulomas, reinforcing its status as a key target in the treatment of immune-mediated diseases.

We are very pleased to have these abstracts, which were originally accepted for presentation at the ATS International Conference, published in the highly-regarded American Journal of Respiratory and Critical Care Medicine, stated Dr. Sanjay Shukla, M.D., M.S., President and Chief Executive Officer of aTyr. The findings summarized in these abstracts confirm the significant role of NRP2 in serious inflammatory diseases, and further elucidate the mechanism of action of ATYR1923 in its ability to selectively bind to this unique target. We look forward to final results from our ongoing Phase 1b/2a clinical trial of ATYR1923 in patients with pulmonary sarcoidosis while in parallel leveraging our numerous research collaborations with biopharmaceutical leaders and academia to further expand our pre-clinical pipeline.

Details of the abstracts are as follows:

P1173 - ATYR1923 Specifically Binds to Neuropilin-2, a Novel Therapeutic Target for the Treatment of Immune-Mediated DiseasesNeuropilin-2 (NRP2) is a pleiotropic cell surface receptor known to be expressed on a number of different immune cell types that plays a key role in regulating inflammatory responses. aTyr Pharmas lead clinical candidate, ATYR1923, is a fusion protein combining a novel immunomodulatory domain from histidyl-tRNA synthetase (HARS) and a human IgG1 Fc. ATYR1923 has previously demonstrated potent immunomodulatory activity in vitro and in vivo. ATYR1923 specifically and selectively binds to NRP2 on the cell surface, which was discovered by cell microarray screening and confirmed by surface plasmon resonance (SPR) and also by flow cytometry analysis of HEK293 cells over-expressing NRP2. Furthermore, ATYR1923 was also found to bind to cells that endogenously express NRP2 on the surface (such as THP-1 polarized M1 macrophages). These findings indicate that modulation of the NRP2 signaling pathway could be a novel therapeutic approach to immune-mediated diseases. ATYR1923 is currently being evaluated in a Phase 1b/2a study in patients with pulmonary sarcoidosis, an inflammatory disease which can result in lung fibrosis.

P983 - Neuropilin-2, the Specific Binding Partner to ATYR1923, Is Expressed in Sarcoid Granulomas and Key Immune CellsaTyr reports for the first time that NRP2 is expressed in samples obtained from lung and skin of sarcoidosis patients. More specifically, NRP2 expression was readily detectable within the granulomas in both skin and lung samples. In this abstract, the company demonstrates that NRP2 expression can be detected on key immune cells known to play an important role in inflammation and granuloma formation. These findings highlight the potential of ATYR1923 to exert its effect on various immune cells directly related to the pathology of the target patient population.

About ATYR1923

aTyr is developing ATYR1923 as a potential therapeutic for patients with interstitial lung diseases. ATYR1923, a fusion protein comprised of the immuno-modulatory domain of histidyl tRNA synthetase fused to the FC region of a human antibody, is a selective modulator of neuropilin-2 that downregulates the innate and adaptive immune response in inflammatory disease states. aTyr is currently enrolling a proof-of-concept Phase 1b/2a trial evaluating ATYR1923 in patients with pulmonary sarcoidosis. This Phase 1b/2a study is a multi-ascending dose, placebo-controlled, first-in-patient study of ATYR1923 that has been designed to evaluate the safety, tolerability, steroid sparing effect, immunogenicity and pharmacokinetics profile of multiple doses of ATYR1923.

About NRP2

Neuropilin-2 (NRP2) is a cell surface receptor that plays a key role in lymphatic development and in regulating inflammatory responses. In many forms of cancer, high NRP2 expression is associated with worse outcomes. NRP2 can interact with multiple ligands and co-receptors through distinct domains to influence their functional roles, making it a potential drug target with multiple distinct therapeutic applications. NRP2 interacts with type 3 semaphorins and plexins to impact inflammation and with forms of vascular endothelial growth factor (VEGF) and their receptors, to impact lymphangiogenesis. In addition, NPR2 modulates interactions between CCL21 and CCR7 potentially impacting homing of dendritic cells to lymphoid organs. aTyr is currently investigating NRP2 receptor biology, both internally and in collaboration with key academic thought leaders, as a novel target for new product candidates for a variety of diseases, including cancer and inflammation.

About aTyr

aTyr is a biotherapeutics company engaged in the discovery and development of innovative medicines based on novel immunological pathways. aTyrs research and development efforts are concentrated on a newly discovered area of biology, the extracellular functionality and signaling pathways of tRNA synthetases. aTyr has built a global intellectual property estate directed to a potential pipeline of protein compositions derived from 20 tRNA synthetase genes and their extracellular targets. aTyrs primary focus is ATYR1923, a clinical-stage product candidate which binds to the neuropilin-2 receptor and is designed to down-regulate immune engagement in interstitial lung diseases. For more information, please visit http://www.atyrpharma.com.

Forward-Looking Statements

This press release contains forward-looking statements within the meaning of the Private Litigation Reform Act. Forward-looking statements are usually identified by the use of words such as anticipates, believes, estimates, expects, intends, may, plans, projects, seeks, should, will, and variations of such words or similar expressions. We intend these forward-looking statements to be covered by such safe harbor provisions for forward-looking statements and are making this statement for purposes of complying with those safe harbor provisions. These forward-looking statements, include statements regarding the potential therapeutic benefits and applications of our product candidates; our ability to successfully advance our product candidates, undertake certain development activities (such as the initiation of clinical trials, clinical trial enrollment, the conduct of clinical trials and the announcement of top-line results) and accomplish certain development goals, and the timing of such events; and the scope and strength of our intellectual property portfolio. These forward-looking statements also reflect our current views about our plans, intentions, expectations, strategies and prospects, which are based on the information currently available to us and on assumptions we have made. Although we believe that our plans, intentions, expectations, strategies and prospects, as reflected in or suggested by these forward-looking statements, are reasonable, we can give no assurance that the plans, intentions, expectations or strategies will be attained or achieved. All forward-looking statements are based on estimates and assumptions by our management that, although we believe to be reasonable, are inherently uncertain. Furthermore, actual results may differ materially from those described in these forward-looking statements and will be affected by a variety of risks and factors that are beyond our control including, without limitation, risks associated with the discovery, development and regulation of our product candidates, the risk that we may cease or delay preclinical or clinical development activities for any of our existing or future product candidates for a variety of reasons (including difficulties or delays in patient enrollment in planned clinical trials), the possibility of unexpected expenses or other demands on our cash resources, and the risk that we may not be able to raise the additional funding required for our business and product development plans, as well as those risks set forth in our most recent Annual Report on Form 10-K, Quarterly Reports on Form 10-Q and in our other SEC filings. Except as required by law, we assume no obligation to update publicly any forward-looking statements, whether as a result of new information, future events or otherwise.

More:
aTyr Pharma Announces Publication of Two Abstracts in American Journal of Respiratory and Critical Care Medicine - BioSpace

A team of doctors and researchers at the Abu Dhabi Stem Cell Center (ADSCC) administered the treatment in the UAE to 73 COVID-19 patients, who were all successfully treated and cured, without any immediate side effects, according to a statement by the United Arab Emirates (UAE) health ministry from 1 May.

The process involved a minimally invasive method where the patients stem cells are extracted, activated and turned into fine mist to be inhaled into the lungs. This was done in addition to the conventional treatment and is expected to work by supporting the established protocol of management of symptoms.

The ministry said in the statement, It is hypothesised to have its therapeutic effect by regenerating lung cells and modulating the immune response to keep it from overreacting to the COVID-19 infection and causing further damage to healthy cells.

The treatment has successfully undergone the initial phase of clinical trials, demonstrating its safety, and further trials for its efficiency are ongoing; expected to be completed in a couple of weeks.

Dr Fatima al-Kaabi, head of haematology and oncology at the Sheikh Khalifa Medical City in the UAE, told CNBC, Its very early to say at this stage. If all went well, this could reach the market in three months, she added.

Going further back, a pilot study in China on seven COVID-19 patients found that intravenous infusions of donor mesenchymal stem cells (MSC) - multipotent stem cells - improved patient outcomes and helped all of them recover. An Israeli pharmaceutical company, Pluristem Therapeutics, also tested stem cells in seven critical hospitalized patients and found positive results.

Additionally, the US Food and Drug Administration (FDA) approved MSC use in extremely sick COVID-19 patients under expanded access compassionate use on 5 April according to a report in The Scientist, even though the experts seemed divided on the logic on which the investigative treatment may have worked.

A hospital in New York tried the therapy as an experiment on 12 patients, 10 of whom were able to come off ventilators, reports CBS news. The Australian regenerative medicine company Mesoblast has also announced a 300-person trial for its stem cell therapy remestemcel-L (which was used in the New York trial) to determine whether it will work on patients suffering with severe lung inflammation.

Currently, there are over 20 active stem cell trials for COVID-19, most focusing on the use of MSCs.

See the original post here:
Stem Cell Treatment for COVID-19; Doctors Divided on Its Scope - The Quint

DUBLIN, May 6, 2020 /PRNewswire/ --Avectas announced that it has exclusively licenced from ONK Therapeutics (ONK) a Chimeric Antigen Receptor-directed Natural Killer (CAR NK) cell therapy incorporating ONK's proprietary Death Receptor (DR5) TRAIL variant for the treatment of B-cell malignancies. Under the collaboration, ONK will be responsible for rapidly progressing the potential therapy to a Phase I clinical trial. The potential therapy will be engineered using Avectas' proprietary non-viral cell engineering platform (Solupore). Avectas will retain worldwide development and commercialization rights to the therapy.

Avectas has also, through a holding company, acquired a minority shareholding in ONK.

The collaboration between the two companies will target the development of a CAR that uses NK cells, optimally engineered (using Avectas' Solupore technology) to both enhance targeting of specific cancer cells and increase therapeutic potency by adding a secondary cancer cell killing mechanism using the DR5 TRAIL variant. If successful, the therapy would be allogeneic allowing for an off-the-shelf solution and its cell-killing effects would be transient to enhance dose control.

Michael Maguire, PhD, CEO of Avectas, commented: "We are excited to collaborate with ONK and its expert team to develop this potentially breakthrough immuno-oncology therapy which seeks to improve on the challenges of scale and potency seen with first generation CAR therapies." He continued, "Solupore was developed to address the urgent need for non-viral cell engineering solutions to support advanced therapies and so this collaboration is a natural next step for our business."

Professor Michael O'Dwyer, CSOof ONK Therapeutics commented: "This exciting collaboration enables us to exploit Avectas' expertise in non-viral gene engineering and will greatly accelerate our efforts to move novel CAR NK cells into the clinic. While early clinical data with CAR NK cells appear promising, resistance is still an issue. Incorporation of our unique proprietary DR5 TRAIL variant into CAR-NK cells provides a powerful, complementary killing mechanism to overcome resistance, which may have applicability in a broad range of cancers."

Terms

Under the terms of the transaction, ONK will receive upfront fees, development and commercial milestones and royalties. Avectas has also, through a holding company, acquired a minority shareholding in ONK.

This collaboration builds on Avectas' recent developments including a Series C funding, the issuance of a key US patent covering Soluporation and new collaborations with Vycellix of Florida, USA, the Centre for Commercialization of Regenerative Medicine (CCRM) in Toronto, Canada and entering the new NK Cell Centre of Excellence at Karolinska Institute, Sweden, as a partner.

The collaboration also builds on ONK Therapeutics' success in securing funding under the Irish Government's Disruptive Technology Innovation Fund (DTIF) call in partnership with the Centre for Cell Manufacturing Ireland, based at NUI Galway.

About Avectas:

Avectas is a cell engineering technology business developing a unique delivery platform to enable the ex-vivo manufacture of gene-modified cell therapy products, which will retain high in-vivo functionality. Our vision is to be a leading non-viral cell engineering technology provider, integrated into manufacturing processes for multiple autologous and allogeneic therapies, commercialized through development and license agreements. For more information, please visithttp://www.avectas.com

About ONK Therapeutics:

ONK Therapeutics was founded in 2015 with the goal of developing novel anti-cancer therapies using Natural Killer (NK) cells. NK cells are one of the body's strongest defences against cancer, being one of the most tumour cytotoxic components of the human immune system. The company's strategy is to develop novel, off the shelf, NK cell-based therapies for cancer. Further, the company is seeking to enhance these NK cells through the introduction of a series of genetic modifications, creating a technology platform that can be tailored to multiple cancers. For more information, please visitwww.onktherapeutics.com

NOTE:

NK cells kill targetted cancer cells, primarily by releasing toxic granules into the cancer cell. TRAIL, a protein expressed on the NK cell also contributes to killing by binding to death receptors (e.g. DR5) on the cell surface. TRAIL variants bind more tightlythan natural TRAIL, generating a much stronger killing signal.Since TRAIL killing does not rely on recognition of a target antigen, TRAIL variants can help prevent the emergence of resistance to CARs.

SOURCE Avectas

Read more:
Avectas and ONK Therapeutics to Develop Off-the-Shelf Cancer Therapy - PRNewswire

Incomplete testing fails to meet current medical guideline standards, placing more than 80 percent1 of patients at increased risk of receiving a less effective treatment

REDWOOD CITY, Calif., May 05, 2020 (GLOBE NEWSWIRE) -- Guardant Health, Inc. (Nasdaq: GH) has launched the Clear Your View campaign to raise awareness of the important role complete biomarker testing plays in guiding initial treatment decisions for newly diagnosed advanced non-small cell lung cancer (NSCLC) patients. Current medical guidelines call for testing all 10 tumor biomarkers in advanced NSCLC.

The campaign encourages oncologists to stop, test, and wait for complete biomarker testing results before starting initial treatment. The campaign is supported by several national patient advocacy groups, including GO2 Foundation for Lung Cancer, LUNGevity Foundation, and ALK Positive. Complete biomarker testing is especially critical given the logistical challenges imposed by the COVID-19 pandemic to ensure that each and every patient is matched with an effective therapy upfront, since targeted therapy options, if appropriate, are often easier or more convenient to administer.

Receiving the right initial treatment can mean the difference between slowing disease progression, and potentially extending survival, said Bonnie J. Addario, Co-Founder, Board Chair, GO2 Foundation for Lung Cancer. While great progress has been made in treating advanced lung cancer, studies show that fewer than 20 percent of patients receive comprehensive guideline-recommended biomarker testing. We must make sure that patients receive the benefit from treatment advances through biomarker testing that matches them to the right therapy.

Clinical studies show that patients receiving targeted or personalized treatments have improved progression-free survival and higher overall response rates compared to chemotherapy or immunotherapy.2-8 Various factors contribute to clinical adoption of personalized medicine lagging behind recommended medical guidelines.1,9-11 Physicians report rapidly changing medical guidelines and the approval of new therapies create an increasingly complex treatment landscape. In addition, patients and physicians want to start treatment as soon as possible. Finally, insurers have been slow to put coverage in place for complete biomarker testing, which may influence the oncologists decision on what biomarker tests to order.

Through the Clear Your View campaign we hope to raise awareness amongst physicians of the clear benefits of complete biomarker testing for patients with NSCLC, said Helmy Eltoukhy, Guardant Health CEO. This campaign calls attention to the risk undergenotyping can have on patient outcomes and the need for complete biomarker testing. Indeed, in this difficult time period, it has never been more critical to match patients with the right therapy the first time.

Lung cancer is by far the leading cause of cancer death among both men and women, making up almost 25 percent of all cancer deaths.12 Each year, more people die of lung cancer than of colon, breast, and prostate cancers combined.12

The campaign is being delivered to over 10,000 oncologists nationwide. The campaign website can be found here.

About ALK Positive OrganizationWe are a patient-driven group, providing information, support, empathy, and research funding to change the future of ALK-Positive lung cancer. ALK Positive consists of 1,800+ ALK-positive lung cancer patients and their caregivers in 42+ countries. Through our foundational online support group, we are able to support each other worldwide and share information to become empowered patients-advocates. https://www.alkpositive.org/treatment-options

About GO2 Foundation for Lung CancerFounded by patients and survivors, GO2 Foundation for Lung Cancer (formerly the Bonnie J. Addario Lung Cancer Foundation and Lung Cancer Alliance), transforms survivorship as the world's leading organization dedicated to saving, extending, and improving the lives of those vulnerable, at risk, and diagnosed with lung cancer. Through our LungMATCH program patients can access free individualized guidance, including referrals for biomarker testing and discussions on treatment and clinical trial options. http://www.go2foundation.org.

About LUNGevity FoundationLUNGevity is the nation's leading lung cancer organization investing in lifesaving, translational research and providingfreesupport services and education for patients and caregivers.LUNGevitys Take Aim Initiative is focused on increasing patient and provider awareness about biomarker testing. https://lungevity.org/for-patients-caregivers/lung-cancer-101/diagnosing-lung-cancer/biomarker-testing

About Guardant HealthGuardant Healthis a leading precision oncology company focused on helping conquer cancer globally through use of its proprietary blood tests, vast data sets and advanced analytics. The Guardant Health Oncology Platform leverages capabilities to drive commercial adoption, improve patient clinical outcomes and lower healthcare costs across all stages of the cancer care continuum.Guardant Healthhas launched liquid biopsy-based Guardant360 and GuardantOMNI tests for advanced stage cancer patients. These tests fuel development of its LUNAR program, which aims to address the needs of early stage cancer patients with neoadjuvant and adjuvant treatment selection, cancer survivors with surveillance, asymptomatic individuals eligible for cancer screening and individuals at a higher risk for developing cancer with early detection.

Forward Looking StatementsThis press release contains forward-looking statements within the meaning of federal securities laws, including statements regarding the potential scope, impact or benefit of the Clear Your View campaign, which involve risks and uncertainties that could cause the actual results to differ materially from the anticipated results and expectations expressed in these forward-looking statements. Such risks and uncertainties include those discussed under the caption Risk Factors in Guardant Healths Annual Report on Form 10-K for the year endedDecember 31, 2019, and in its other reports filed with theSecurities and Exchange Commission, including in its Quarterly Report on Form 10-Q for the period ended March 31, 2020, when filed. These forward-looking statements are based on current expectations, forecasts, assumptions and information available toGuardant Healthas of the date hereof, and actual outcomes and results could differ materially from these statements due to a number of factors, andGuardant Healthdisclaims any obligation to update any forward-looking statements provided to reflect any change in its expectations or any change in events, conditions, or circumstances on which any such statement is based, except as required by law. These forward-looking statements should not be relied upon as representing Guardant Healths views as of any date subsequent to the date of this press release. Investors are urged not to rely on any forward-looking statement in reaching any conclusion or making any investment decision about any securities ofGuardant Health.

Investor Contact:

Carrie Mendivilinvestors@guardanthealth.com

Media Contacts:

Anna Czene press@guardanthealth.com

Becky Lauerbecky.lauer@uncappedcommunications.com

References:

Continue reading here:
Guardant Health and Patient Advocacy Groups Join Forces to Raise Awareness of the Importance of Complete Biomarker Testing for Patients with...

More than 200,000 people have died from COVID-19 since January 2020. While Australia has been relatively spared from the onslaught of infections and deaths, our nations scientists need to be part of the global effort to address this pandemic.

Research Group Head, Amnion Cell Biology

There is no effective treatment to address the ongoing damage caused by for severe COVID-19 infections, said Associate Professor Rebecca Lim, Research Group Head of Amnion Cell Biology at Hudson Institute. Our team is investigating whether a cell therapy can be effective.

Amniotic epithelial cells (amnion cells) are from the amniotic sac which surrounds a baby during pregnancy. They have stem cell-like properties and can grow into many cell types. Most importantly, they have potent effects on inflammation and tissue damage.

A/Prof Lim and Professor Euan Wallace (Clinical Director, The Ritchie Centre) are developing a clinical trial to investigate whether these cells can help treat patients with COVID-19.

The team is working closely with intensivists at Monash Healths Intensive Care Unit to deliver a Phase 1b/2a clinical trial for COVID-19 positive patients requiring hospitalisation.

The goal of the trial is to determine if allogeneic amniotic epithelial cells are an effective therapy for severe COVID-19 complications. Specifically, the trial will test whether the cells can significantly reduce the cytokine storm associated with COVID-19 infection, encourage lung tissue to repair, and reduce the incidence of blood clotting and subsequent multi-organ complications including strokes, liver and kidney failure.

We have already shown that the allogeneic amniotic epithelial cells are safe and well-tolerated in extremely premature neonates and acutely unwell adults. So far, we have observed improvements in adult patients with liver disease and severe stroke. This points to the likely benefits for patients with COVID-19. These cells may also reduce the incidence and severity of the disease damage caused by blood clotting in tissues, A/Prof Lim said.

This project involves a partnership between Hudson Institute, Monash Health and Monash University-a team that leads the way in Victoria in cell therapy clinical trials targeting inflammation and regenerative medicine.

Victoria is perfectly placed to deliver a cell therapy treatment for COVID-19, A/Prof Lim said.

However, the trial requires funding.

The other trials using our cell-based therapies are in

Go here to read the rest:
Cell therapies trial planned for COVID-19 - Mirage News

Wellcome Sanger Institute scientists have helped to identify two specific cell types in the nose that are likely initial infection points for the Covid-19 virus.

The study could help to explain why it has such a high transmission rate - and reveals potential targets for tackling the problem.

The researchers discovered that goblet and ciliated cells in the nose have high levels of entry proteins that the virus uses to get into our cells. They also found that cells in the eye and some other organs contain viral-entry proteins.

The study, published in Nature Medicine, also predicts how a key entry protein is regulated with other immune system genes.

The work is part of the ongoing international effort to use data from the Human Cell Atlas (HCA) - the project creating reference maps of all human cells - to understand infection and disease.

It is the first publication with the Lung Biological Network - a consortium of 71 scientistscollaborating to map the airway cells in our body.

Dr Sarah Teichmann, a senior author from the Wellcome Sanger Institute and co-chair of the HCA organising committee, said: As were building the Human Cell Atlas, it is already being used to understand Covid-19 and identify which of our cells are critical for initial infection and transmission.

This information can be used to better understand how coronavirus spreads. Knowing which exact cell types are important for virus transmission also provides a basis for developing potential treatments to reduce the spread of the virus.

The SARS-CoV-2 virus that causes Covid-19 uses a similar mechanismto infect our cells as the related coronavirus that caused the 2003 SARS epidemic.

A spike on the outside of the virus acts like a key to unlock an ACE2 (angiotensin converting enzyme II) receptor protein on the human cell.

A second protein inside the cell known as the TMPRSS2 protease is then used to complete entry, which then allows the virus to reproduce and transmit itself.

However, until now the exact cell types involved in the nose had not previously been confirmed.

Dr Waradon Sungnak, the first author on the paper from Wellcome Sanger Institute, said: We found that the receptor protein - ACE2 - and the TMPRSS2 protease that can activate SARS-CoV-2 entry are expressed in cells in different organs, including the cells on the inner lining of the nose.

We then revealed that mucus-producing goblet cells and ciliated cells in the nose had the highest levels of both these Covid-19 virus proteins, of all cells in the airways. This makes these cells the most likely initial infection route for the virus.

From there, the novel coronavirus can affect the airways and lungs.

The virus - which has spread to more than 184 countries - is thought to be spread via respiratory droplets released when an infected person coughs or sneezes.

The researchers analysed multiple Human Cell Atlas consortium datasets of single cell RNA sequencing from more than 20 different tissues of non-infected people.

Cells from the lung, nasal cavity, eye, gut, heart, kidney and liver were examined, and the researchers studied which individual cells expressed both of two key entry proteins that are used by the virus to infect our cells.

Speaking on behalf of the HCA Lung Biological Network, Dr Martijn Nawijn, from the University Medical Center Groningen in the Netherlands, said: This is the first time these particular cells in the nose have been associated with Covid-19.

While there are many factors that contribute to virus transmissibility, our findings are consistent with the rapid infection rates of the virus seen so far.

The location of these cells on the surface of the inside of the nose make them highly accessible to the virus, and also may assist with transmission to other people.

The study suggests that ACE2 receptor production in the nose cells is probably switched on at the same time as other immune genes that are activated when cells are damaged or fighting infection.

The researchers also found the key entry proteins ACE2 and TMPRSS2 in cells in the cornea of the eye and in the lining of the intestine.

The finding suggests another possible route of infection via the eye and tear ducts - and raises the potential of fecal-oral transmission.

The HCA Lung Biological Network is continuing to analyse the data - available at https://www.covid19cellatlas.org/ - for further insights into the cells and targets likely to be involved in Covid-19 and to relate them to patient characteristics.

Prof Jayaraj Rajagopal, a member of the network and pulmonologist in the Department of Internal Medicine at Massachusetts General Hospital, said: The cellular basis of disease often does not receive as much attention as the molecular basis of disease, even though molecules and cells are inseparably linked. In the case of Covid-19, knowing the cells that act as portals of viral entry and possible viral reservoirs helps us think about why a virus can be transmitted easily between people and why only some people progress to a lethal pneumonia.

Most studies of coronaviruses dont use cells from the actual tissues that are infected in patients.The HCA hopes to point both virologists and physicians toward the right cells and tissues for study.

All the data from the Human Cell Atlas - involving 1,600 people in 70 countries - is openly available to scientists across the globe.

Professor Sir Jeremy Farrar, director of Wellcome, said: By pinpointing the exact characteristics of every single cell type, the Human Cell Atlas is helping scientists to diagnose, monitor and treat diseases including Covid-19 in a completely new way. Researchers around the world are working at an unprecedented pace to deepen our understanding of Covid-19, and this new research is testament to this.

Collaborating across borders and openly sharing research is crucial to developing effective diagnostics, treatments and vaccines quickly, ensuring no country is left behind.

Joining the Sanger Institute at Hinxton on this study were researchers from University Medical Centre Groningen, University Cote dAzur and CNRS, Nice and their collaborators.

Read more

20m Covid-19 alliance led by University of Cambridge and Wellcome Sanger Institute will use genomics to fight coronavirus

Worlds first cell atlas of developing liver created by Cambridge scientists

University of Cambridge study finds link between high levels of air pollution and deadlier cases of Covid-19

AI VIVO identifies list of 31 drugs that show potential for Covid-19 treatment

Go here to see the original:
Sanger Institute researchers help identify the nose cells that act as entry points for the Covid-19 virus - Cambridge Independent

February 2020

Are you looking for a health care provider who offers innovative alternatives and a customized approach to your health issues? Indiana Regenerative Medicine Institute (IRMI) believes in offering specialized alternatives to health care. Its medical team, headed by Doctor of Chiropractic Preston Peachee, utilizes the latest developments in regenerative medicine, hormone replacement and pain management.

Dr. Peachee is a native of Jasper, Indiana. He graduatedfrom Logan College of Chiropractic and has been in practice since 2003. Hisareas of specialty include patients with chronic and severe back, neck andjoint pain as well as other complex neurological conditions.

Dr. Peachee has earned a reputation as an innovative thinkeras well as a compassionate practitioner who brings his wide expertise andexperience to the Greater Indianapolis area. His ability to help those in needof regenerative medicine, neuropathy pain relief, low testosterone or otherphysical ailments, such as back pain or fibromyalgia, makes him not only uniquebut highly sought-after.

A key member of the IRMI team is Leann Emery, FNP. Emery isa family nurse practitioner with more than 20 years of experience in hormonereplacement and alternative pain management. Emery provides optimal patientcare through personal consultations and assessments to identify her patientsspecific health needs. She was rated in the top 10% of providers in the U.S.with patient satisfaction.

Regenerative medicine is making huge leaps in our understanding of the human body, and it is offering real, possible treatments that would have seemed like science fiction a few short years ago, according to IRMI. Most patients we see have tried other more traditional treatments and have either not gotten any better or have gotten even worse. Unfortunately, a lot of people we see depend on multiple medications per day to try and function but still are not happy with how they feel or how they live their lives. It is unfortunately the nature of deteriorating and degenerative joints, they will get worse with time, and generally the pain increases as well.

Depending on the injury, Dr. Peachee will often combinelaser therapy with the regenerative medicine protocols to improve the outcomesand try and speed the recovery process.

We offer mesenchymal stem cell therapy, Dr. Peachee said. With the combination of laser therapy, mesenchymal stem cell therapy is incredibly effective for rotator cuff problems and treating knee pain. Eighty percent of our stem patients are dealing with knee pain or Osteoarthritis. Osteoarthritis-or O.A. of the knee- is a huge problem for a lot of people, and we get great results from these therapies. Most people can even avoidknee surgery.

Dr. Peachee recently introduced hormone treatments for low testosterone. Family Nurse Practitioner Leann Emery has been doing [hormone] treatments for 20 years, and that area of medicine became a natural fit for IRMI.

I have several patients who were seeking this type ofcaremany who are police officers and firefighterswho couldnt find thetherapy and individualized care and attention that they needed.

Dr. Peachee explained that low T treatments help patients with unique and even complicated cases of Erectile Dysfunction (E.D.). Most people seek us out for treatment because they are tired, worn out, stressed out and just simply lack the energy they used to have.

We are able to fill a niche with patients who hadcomplicated cases that were not responding well with their primary careproviders or other places, Dr. Peachee shared. We have a patient who hasstruggled for a long time with fertility issues but has done very well [withtreatments], and we just got good news that he and his wife are expecting aftertrying for a really long time. So, he is really enthused about that.

The typical candidates for low T treatments, according toDr. Peachee, are men who feel worn out, are lethargic and have lost theirzest for life.

Our patients dont have the same pep that they had 10 or20 years ago, Dr. Peachee stated. They struggle getting up in the morning andmight be struggling in the afternoon after having six cups of coffee or threeRed Bulls just to get through the day. We have a lot of people that want to getback into the gym and get the maximum benefit of their workouts. We can helpthem improve their overall health and energy so that they can enjoyrecreational activities like working out or practice with the Little Leaguewith their kids. Many times we hear from spouses, friends and family how muchbetter they feel and that they seem happier and get more out of life again.

It goes without saying that proper hormonal balance canimprove a patients personal relationships as well and improve the overallmental health of a patient by reducing stress, anxiety and depression oftencaused by symptoms related to low testosterone levels.

We focus on injectable [low T] treatments because we canmodify the dosage and give more frequent doses to keep our patients at a levelthats going to give them the maximum benefit and improvement for theirconditions, Dr. Peachee explained.

With the modern changes in medicine over the last 20 and 50years, were helping people to live a lot longer and adding 20 to 30 years totheir lives, but we have not given them an improved quality of life as theyage. By working with their hormones and getting them in balance, their qualityof life becomes way better, and were seeing a positive improvement for manypeople with these treatments.

Patients suffering from severe disc injuries, such a bulgingor herniated disc or discs, or who suffer from degenerative disc disease mayhave undergone treatment from chiropractors or have seen physical therapistsbefore coming to Indiana Regenerative Medicine Institute.

Our typical patient who comes in for this type of treatmenthas seen other therapists or chiropractors but hasnt found lasting relief,Dr. Peachee said. Many of our patients want to get off the rollercoaster ofopioids and pain medications. They are looking for a solution without narcoticsand risk of addiction or other possible negative side effects of narcoticsand/or surgery. We are generally able to alleviate the pain in 90% of patientsand are able to keep them from having surgery or from taking addictivemedications.

Laser therapy allows Dr. Peachee to work on the damaged tissue so that it can heal, and the method reduces inflammation and swelling in a way that traditional treatments cannot.

Its an innovative new therapy within the last decade thatallows us to do some amazing things, Dr. Peachee stated. We perform ourprocedures in our office and have several different devices for the specificneeds and issues of our patients. For instance, we have a unique device forpeople with knee pain that can help the majority of our patients walk betterand live more pain-free. We get a phenomenal outcome with this procedure.

One of the other major differentiators that sets IndianaRegenerative Medicine Institute apart from other offices and clinics is thatthey are advocates for their patients, especially when it comes to dealing withtheir patients insurance providers.

A lot of our low T patients are able to get their insurancecarriers to cover the services so that it doesnt cost them as much out ofpocket for the care they seek, Dr. Peachee said. Weve partnered with abilling company that has helped us to be able to navigate the craziness of ourmodern insurance companies, and by doing so, were able to keep the cost downfor a lot of patients. Not every insurance plan will cover this type of care,but a lot of them will. When its possible and ethical, we do whatever we canto benefit our patients to help keep the cost low. I have spent a lot of freetime writing letters on behalf of our patients. We go above and beyond with ourservice and care of our patients.

The Indiana Regenerative Medicine Institute team will make housecalls or come to a patients place of work when the situation calls for thatlevel of care.

We will go and draw blood for blood work, bring medications and even do exams in some situations, Dr. Peachee said. As I mentioned before, we see a lot of police officers and firemen all over the statefrom Mishawaka to South Bend and all over Indiana. We go once a month to see these patients at their departments and stations so that we see them all in one day versus making 10 to 15 guys drive hours to come in to see us. Its a service we can offer because we are a small clinic and we are focused on that one-on-one patient attention and relationship building. We have great relationships with our patients, and thats something that we work very hard at.

Building trust and transparency is crucial to the success ofhis practice, Dr. Peachee emphasized. The trust that we build with ourpatients is crucial to not only the success of the practice but to thepatients outcomes. And not just with hormone therapy but also with ournonsurgical spinal decompression patients. These are patients with significant discinjuries, and we need them to tell us everything we need to know so we can givemore accurate and complete care for a better outcome.

I would say to anybody if you have any doubts or reservations to take some of the burden and some of the anxiety out of the equation and schedule an initial consultationabsolutely free of charge, Dr. Peachee encouraged.

Dont put off living your best life any longer. Visit Indiana Regenerative Medicine Institutes website at indianaregen.com or call (317) 653-4503 for more information about its services and specialized treatments and schedule your free consultationtoday!

Writer:

Janelle Morrison

Photography:

Laura Arick and submitted

More:
Indiana Regenerative Medicine Institute Offers Innovative Approaches in Regenerative Medicine, Hormone Replacement and Pain Management - Zionsville...