Category Archives: Immunology

Immunology

Pandion Therapeutics to Participate in Panel Discussion at Stifel 2020 Immunology & Inflammation Virtual Summit – BioSpace

WATERTOWN, Mass., Sept. 24, 2020 (GLOBE NEWSWIRE) -- Pandion Therapeutics, Inc. (Nasdaq: PAND), a clinical-stage biotechnology company developing novel therapeutics designed to address the unmet needs of patients living with autoimmune diseases, today announced that Rahul Kakkar, M.D., Chief Executive Officer of Pandion Therapeutics, will participate in a panel discussion at the upcoming Stifel Immunology & Inflammation Summit on Thursday, October 1, 2020 at 3:00 p.m. ET.

A live audio webcast of the panel will be available on the Investors and News section of Pandion Therapeutics investor website at https://investors.pandiontx.com/. A replay of the webcast will be available shortly following the presentation.

About Pandion TherapeuticsPandion Therapeuticsis developing novel therapeutics designed to address the unmet needs of patients living with autoimmune diseases. Pandions TALON (Therapeutic Autoimmune reguLatOry proteiN) drug design and discovery platform enables the company to create a pipeline of product candidates using immunomodulatory effector modules, with the ability to also combine an effector module with a tissue-targeted tether module in a bifunctional format.Pandions lead product candidate PT101, a combination of an interleukin-2 mutein effector module with a protein backbone, is designed to selectively expand regulatory T cells systemically, without activating proinflammatory cells, such as conventional T cells and natural killer cells, is currently in a Phase 1a clinical trial. Pandion is continuing to develop and expand its library of effector and tether modules as part of its earlier-stage research and discovery pipeline. For more information, please visitwww.pandiontx.com.

For further information, please contact:

Media:Kathryn MorrisThe Yates Network914-204-6412kathryn@theyatesnetwork.com

Investors:Michelle AveryPandion Therapeuticsinvestors@pandiontx.com

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Pandion Therapeutics to Participate in Panel Discussion at Stifel 2020 Immunology & Inflammation Virtual Summit - BioSpace

Immunology

Study reveals higher incidence of immunology diseases in donor sperm-conceived adults – News-Medical.Net

Reviewed by Emily Henderson, B.Sc.Sep 24 2020

Adults conceived through sperm donation reported higher frequencies of allergies, type 1 diabetes and other autoimmune conditions in a world-first study that examined the long term health outcomes of donor-conceived people.

The study was conducted by Flinders University's Caring Futures Institute, led by researcher Damian Adams, and published in the Journal of Developmental Origins of Health and Disease. It looked at 272 donor-conceived adult participants from around the world together with 877 who were conceived naturally.

Results revealed that for most health outcomes, donor sperm conceived adults reported no significant difference to participants born through natural conception.

However, donor sperm conceived adults had seven times more type 1 diabetes diagnoses than naturally conceived adults, together with double the incidence of thyroid disease, acute bronchitis and sleep apnoea; and a 45% incidence of allergies compared to 35% in the naturally conceived population.

Mr Adams says most of the health conditions reported by donor conceived people had an immunological basis, suggesting an alteration to their immunological systems.

What may potentially be driving this is the maternal complication of preeclampsia, which has increased incidences associated with the use of donated gametes (sex cells).

Preeclampsia is an extremely serious condition that is mediated by the immune system. Research has shown that children born from a pregnancy complicated by preeclampsia have altered epigenetic profiles including links with an altered immune system."

Damian Adams, Researcher, Flinders University

Mr Adams is a PhD candidate at Flinders University, whose interest in the health outcomes of donor-conceived people was sparked by vast knowledge gaps in the area.

His supervisors include Flinders University Professor Sheryl de Lacey, who has a clinical background in infertility and assisted reproductive technology.

She says the use of donor gametes has been cloaked in secrecy and abetted by anonymity, with pregnancies assumed to be no different to natural conceptions.

"Being aware of an increased risk of pre-eclampsia in pregnancy and the implications for children in adulthood holds the potential to empower women beyond their pregnancy," Professor de Lacey says.

"For parents, this unique study provides important information that informs their decision of whether to disclose conception means to their child, and to choose the health care they receive.

For donor-conceived people, having this information may improve vigilance in preventative health behaviors."

Mr Adams says donor-conceived people are a hard to reach population, with research consistently showing that the majority do not know they were conceived by sperm donation.

"We had to implement six different recruitment strategies to attract the sample size we achieved," he says.

The majority of participants were from Australia, the United States, the United Kingdom, Belgium and the Netherlands.

Those conceived by donor or through natural conception were matched for age, sex, height, smoking habits, alcohol consumption, exercise and fertility.

"This study was preceded by our systematic review of the literature, where we noted a dearth of studies investigating the perinatal and long-term health outcomes of donor sperm treatments, despite the technique being used for almost 140 years," Mr Adams says.

Source:

Journal reference:

Adams, D.H., et al. (2020) Self-reported physical health status of donor sperm-conceived adults. Journal of Developmental Origins of Health and Disease. doi.org/10.1017/S204017442000080X.

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Study reveals higher incidence of immunology diseases in donor sperm-conceived adults - News-Medical.Net

Immunology

Catalyst Biosciences to Present at the Stifel Immunology and Inflammation Summit – Yahoo Finance

TipRanks

Markets are volatile, there can be no doubt. So far this month, the S&P 500 has fallen 9% from its peak. The tech-heavy NASDAQ, which had led the gainers all summer, is now leading the on the fall, having lost 11% since September 2. The three-week tumble has investors worried that we may be on the brink of another bear market.The headwinds are strong. The usual September swoon, the upcoming election, doubts about another round of economic stimulus all are putting downward pressure on the stock markets.Which doesnt mean that there are no opportunities. As the old saw goes, Bulls and bears can both make money, while the pigs get slaughtered. A falling market may worry investors, but a smart strategy can prevent the portfolio from losing too much long-term value while maintaining a steady income. Dividend stocks, which feed into the income stream, can be a key part of such a strategy.Using the data available in the TipRanks database, weve pulled up three stocks with high yields from 7% to 11%, or up to 6 times the average dividend found on the S&P 500 index. Even better, these stocks are seen as Strong Buys by Wall Streets analysts. Lets find out why.Williams Companies (WMB)We start with Williams Companies, an Oklahoma-based energy company. Williams controls pipelines connecting Rocky Mountain natural gas fields with the Pacific Northwest region, and Appalachian and Texan fields with users in the Northeast and transport terminals on the Gulf Coast. The companys primary operations are the processing and transport of natural gas, with additional ops in crude oil and energy generation. Williams handles nearly one-third of all US commercial and residential natural gas use.The essential nature of Williams business really, modern society simply cannot get along without reliable energy sources has insulated the company from some of the economic turndown in 1H20. Quarterly revenues slid from $2.1 billion at the end of last year to $1.9 billion in Q1 and $1.7 billion in Q2. EPS in the first half was 26 cents for Q1 and 25 cents for Q2 but this was consistent with EPS results for the previous three quarters. The generally sound financial base supported the companys reliable dividend. Williams has been raising that payment for the past four years, and even the corona crisis could not derail it. At 40 cents per common share, the dividend annualizes to $1.60 and yields an impressive 7.7%. The next payment is scheduled for September 28.Truist analyst Tristan Richardson sees Williams as one of the midstream sectors best positioned companies.We continue to look to WMB as a defensive component of midstream and favor its 2H prospects as broader midstream grasps at recovery Beyond 2020 we see the value proposition as a stable footprint with free cash flow generation even in the current environment. We also see room for incremental leverage reduction throughout our forecast period on scaled back capital plans and even with the stable dividend. We look for modestly lower capex in 2021, however unlike more G&P oriented midstream firms, we see a project backlog in downstream that should support very modest growth, Richardson noted.Accordingly, Richardson rates WMB shares as a Buy, and his $26 price target implies a 30% upside potential from current levels. (To watch Richardsons track record, click here)Overall, the Strong Buy analyst consensus rating on WMB is based on 11 Buy reviews against just a single Hold. The stocks current share price is $19.91 and the average price target is $24.58, making the one-year upside potential 23%. (See WMB stock analysis on TipRanks)Magellan Midstream (MMP)The second stock on our list is another midstream energy company, Magellan. This is another Oklahoma-based firm, with a network of assets across much of the US from the Rocky Mountains to the Mississippi Valley, and into the Southeast. Magellans network transports crude oil and refined products, and includes Gulf Coast export shipping terminals.Magellan's total revenues rose sequentially to $782.8 in Q1, and EPS came in at $1.28, well above the forecast. These numbers turned down drastically in Q2, as revenue fell to $460.4 million and EPS collapsed to 65 cents. The outlook for Q3 predicts a modest recovery, with EPS forecast at 85 cents. The company strengthened its position in the second quarter with an issue of 10-year senior notes, totaling $500 million, at 3.25%. This reduced the companys debt service payments, and shored up liquidity, making possible the maintenance of the dividend.The dividend was kept steady at $1.0275 per common share quarterly. Annualized, this comes to $4.11, a good absolute return, and gives a yield of 11.1%, giving MMP a far higher return than Treasury bonds or the average S&P-listed stock.Well Fargo analyst Praneeth Satish believes that MMP has strong prospects for recovery. [We] view near-term weakness in refined products demand as temporary and recovering. In the interim, MMP remains well positioned given its strong balance sheet and liquidity position, and ratable cash flow stream Satish goes on to note that the dividend appears secure for the near-term: The company plans to maintain the current quarterly distribution for the rest of the year.In line with this generally upbeat outlook, Satish gives MMP an Overweight (i.e. Buy) rating, and a $54 price target that implies 57% growth in the coming year. (To watch Satishs track record, click here)Net net, MMP shares have a unanimous Strong Buy analyst consensus rating, a show of confidence by Wall Streets analyst corps. The stock is selling for $33.44, and the average price target of $51.13 implies 53% growth in the year ahead. (See MMP stock analysis on TipRanks)Ready Capital Corporation (RC)The second stock on our list is a real estate investment trust. No surprise finding one of these in a list of strong dividend payers REITs have long been known for their high dividend payments. Ready Capital, which focuses on the commercial mortgage niche of the REIT sector, has a portfolio of loans in real estate securities and multi-family dwellings. RC has provided more than $3 billion in capital to its loan customers.In the first quarter of this year, when the coronavirus hit, the economy turned south, and business came to a standstill, Ready Capital took a heavy blow. Revenues fell by 58%, and Q1 EPS came in at just one penny. Things turned around in Q2, however, after the company took measures including increasing liquidity, reducing liabilities, and increasing involvement in government-sponsored lending to shore up business. Revenues rose to $87 million and EPS rebounded to 70 cents.In the wake of the strong Q2 results, RC also started restoring its dividend. In Q1 the company had slashed the payment from 40 cents to 25 cents; in the most recent declaration, for an October 30 payment, the new dividend is set at 30 cents per share. This annualizes to $1.20 and gives a strong yield of 9.9%.Crispin Love, writing from Piper Sandler, notes the companys success in getting back on track.Given low interest rates, Ready Capital had a record $1.2B in residential mortgage originations versus our $1.1B estimate. Gain on sale margins were also at record levels. We are calculating gain on sale margins of 3.7%, up from 2.4% in 1Q20, Love wrote.In a separate note, written after the dividend declaration, Love added, We believe that the Board's actions show an increased confidence for the company to get back to its pre-pandemic $0.40 dividend. In recent earnings calls, management has commented that its goal is to get back to stabilized earnings above $0.40, which would support a dividend more in-line with pre-pandemic levels.To this end, Love rates RC an Overweight (i.e. Buy) along with a $12 price target, suggesting an upside of 14%. (To watch Loves track record, click here)All in all, Ready Capital has a unanimous Strong Buy analyst consensus rating, based on 4 recent positive reviews. The stock has an average price target of $11.50, which gives a 9% upside from the current share price of $10.51. (See RC stock analysis on TipRanks)To find good ideas for dividend stocks trading at attractive valuations, visit TipRanks Best Stocks to Buy, a newly launched tool that unites all of TipRanks equity insights.Disclaimer: The opinions expressed in this article are solely those of the featured analysts. The content is intended to be used for informational purposes only. It is very important to do your own analysis before making any investment.

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Catalyst Biosciences to Present at the Stifel Immunology and Inflammation Summit - Yahoo Finance

Immunology

TL1A and its receptor could reduce fibrosis and tissue remodeling in patients with severe lung disease – News-Medical.Net

Reviewed by Emily Henderson, B.Sc.Sep 25 2020

Your lungs and airways need to be stretchy, sort of like balloons. Take a big breath, and they'll open right up.

Damaged lungs can't open properly. Patients with asthma, idiopathic pulmonary fibrosis and systemic sclerosis suffer from fibrosis and tissue remodeling, where a build-up of tissue and immune cells, and proteins that form a glue-like substance, keep the airways from expanding. As fibrosis gets worse, taking a breath feels like blowing up a balloon filled with concrete.

In a new study, researchers at La Jolla Institute for Immunology (LJI) report that a protein called TL1A drives fibrosis in several mouse models, triggering tissue remodeling, and making it harder for lungs and airways to function normally.

"Our new study suggests that TL1A and its receptor on cells could be targets for therapeutics aimed at reducing fibrosis and tissue remodeling in patients with severe lung disease," says LJI Professor Michael Croft, Ph.D., director of scientific affairs at LJI and senior author of the new study in The Journal of Immunology.

Croft's laboratory is focused on understanding the importance of a family of proteins, called tumor necrosis factors (TNF) and tumor necrosis factor receptors (TNFR), in inflammatory and autoimmune diseases. By investigating these molecules, researchers hope to track down the root causes of inflammation and stop tissue damage before it's too late.

Previous research had shown that a TNF protein called TL1A can act on immune cells involved in allergic reactions and drive those immune cells to make inflammatory molecules. The Croft Lab wondered-;if TL1A leads to inflammation, could it contribute to fibrosis in the lungs?

For the new study, Croft and his colleagues used genetic and therapeutic interventions, tissue staining, and fluorescence imaging techniques to study protein interactions in mouse models of severe asthma, idiopathic pulmonary fibrosis and systemic sclerosis. They first discovered that TL1A acts directly on a receptor on cells in the lungs and bronchial tubes, which leads to fibrosis and tissue remodeling.

We're all familiar with the idea of tissue remodeling. When a wound on the skin heals, the new area of skin is sometimes shiner, darker or tougher than the skin around it.

The tissue has been remodeled. When lungs and airways try to heal-;in response to an asthma attack, for example-; the cells in the area also change. The damaged area accumulates cells called fibroblasts, which make several glue-like proteins, including collagen. Too much collagen makes the lungs and airways less elastic-;and less functional.

As Croft describes it, tissue remodeling is like wound healing, "but wound healing that goes wrong and becomes so exaggerated that it blocks tissue from behaving in its normal way." With the new study, scientists now know that TL1A is driving this harmful remodeling in the lungs.

In addition to causing fibroblasts to make collagen, the researchers found that TL1A also helps fibroblasts to behave like smooth muscle cells.

A thin layer of smooth muscle cells naturally lines the bronchial tubes allowing them to dilate and constrict, but a thick layer of these smooth muscle cells-;that includes fibroblasts-;will keep the airways from expanding and contracting normally, making it even hard for a patient to breathe.

The scientists then studied lung tissue remodeling in mice that lacked the receptor for TL1A, called DR3, or were given a reagent that blocked TL1A activity. These mice showed less lung remodeling, less collagen deposition and reduced smooth muscle mass in the lungs.

These animal model data may support recent research in humans. Researchers have found that patients with severe asthma have excessive production of TL1A. This could explain why these patients are more vulnerable to lung fibrosis and remodeling.

This type of research needs to be expanded to really understand if there are subsets of patients with asthma or other inflammatory lung diseases who might express TL1A at higher levels than other patients-;which could potentially guide future therapies for targeting TL1A to reduce remodeling and fibrosis."

Michael Croft, PhD, Professor and Study Senior Author, Director of Scientific Affairs, La Jolla Institute for Immunology

Going forward, Croft and his team plan to investigate how the DR3 receptor is expressed on tissue cells and whether it is affected by other inflammatory factors. They also want to know how active TL1A is in human patients and how many inflammatory activities the protein might be responsible for.

Source:

Journal reference:

Herro, R., et al. (2020) TL1A Promotes Lung Tissue Fibrosis and Airway Remodeling. Journal of Immunology. doi.org/10.4049/jimmunol.2000665.

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TL1A and its receptor could reduce fibrosis and tissue remodeling in patients with severe lung disease - News-Medical.Net

Immunology

The Tisch Cancer Institute Earns Second Consecutive Designation from National Cancer Institute – Newswise

Newswise New York, NY (September 24, 2020) The Tisch Cancer Institute at Mount Sinai (TCI) has been awarded $13 million as part of the renewal of its National Cancer Institute Cancer Center Designation, a prestigious distinction that is based on scientific excellence, robust clinical research, and beneficial community impact. The National Cancer Institute rated TCIs application as outstanding.

The five-year redesignation awardthe Institutes second consecutive designationwill support research programs and facilities, promote collaborative translational cancer research in a coordinated manner, and help disseminate cancer research findings to the community. The funding complements $53 million in current cancer research grants earned by TCI investigators.

The strategic plan that helped lead to the redesignation this year included cutting-edge clinical research developed by teams from several disciplines, allowing TCI to provide personalized care to the New York City metro areas diverse communities. Four areas in which TCI researchers and physicians excel, and which contributed to the redesignation, include:

TCI was first named an NCI-designated cancer center in 2015. Since then, the recruitment of leaders in cancer genomics, lung cancer, cancer immunology, and clinical research, and the exponential growth of clinical trials originated by Mount Sinai physicians, has helped bolster the cancer centers national prominence and continued to bring cutting-edge research from the lab to the bedside of Mount Sinai patients.

The NCI redesignation recognizes our plan to maximize our ability to make an impact in our community and at the national level over the next five years, expanding on our successes in four key areas: cancer immunology, cancer mechanisms, cancer clinical investigation, and cancer prevention and control, said Ramon Parsons, MD, PhD, Director of The Tisch Cancer Institute at Mount Sinai, Ward-Coleman Chair in Cancer Research, and Chair of Oncological Sciences at the Icahn School of Medicine at Mount Sinai. Our patients are the beneficiaries of our commitment to advancing scientific research in cancer and harnessing our findings into new therapies and prevention initiatives.

Some achievements in the four key areas include:

Our physicians have built up a repertoire of investigator-initiated trials and novel clinical research studies, which contributed to this redesignation and has become a strength of The Tisch Cancer Institute, said William K. Oh, MD, Deputy Director of The Tisch Cancer Institute, Chief of the Division of Hematology and Medical Oncology at the Mount Sinai Health System, and the Ezra M. Greenspan, MD, Professor in Clinical Cancer Therapeutics at the Icahn School of Medicine at Mount Sinai. Another strength that sets us apart is our research on cancer in World Trade Center responders, due to our unique position of having a monitoring program at Mount Sinai. Our research has led to insights into how inflammation leads to cancer as well as which cancers should be investigated in this vulnerable population.

The Tisch Cancer Institute at Mount Sinai investigates real-world, complex medical problems and solves them with teams of scientists and physicians that successfully integrate many disciplines, said Dennis S. Charney, MD, Anne and Joel Ehrenkranz Dean of the Icahn School of Medicine at Mount Sinai and President for Academic Affairs of the Mount Sinai Health System. The NCI redesignation underscores our exceptional leadership, extensive research facilities, and an institution-wide commitment to research with a focus on identifying and combatting disparities so that all patients receive the best care possible.

About the Mount Sinai Health System

The Mount Sinai Health System is New York City's largest academic medical system, encompassing eight hospitals, a leading medical school, and a vast network of ambulatory practices throughout the greater New York region. Mount Sinai is a national and international source of unrivaled education, translational research and discovery, and collaborative clinical leadership ensuring that we deliver the highest quality carefrom prevention to treatment of the most serious and complex human diseases. The Health System includes more than 7,200 physicians and features a robust and continually expanding network of multispecialty services, including more than 400 ambulatory practice locations throughout the five boroughs of New York City, Westchester, and Long Island. The Mount Sinai Hospital is ranked No. 14 onU.S. News & World Report's"Honor Roll" of the Top 20 Best Hospitals in the country and the Icahn School of Medicine as one of the Top 20 Best Medical Schools in country. Mount Sinai Health System hospitals are consistently ranked regionally by specialty and our physicians in the top 1% of all physicians nationally byU.S. News & World Report.

For more information, visithttps://www.mountsinai.orgor find Mount Sinai onFacebook,TwitterandYouTube.

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The Tisch Cancer Institute Earns Second Consecutive Designation from National Cancer Institute - Newswise

Immunology

STING: A hot target in immunology research and drug discovery – BioWorld Online

The importance of the stimulator of interferon genes (STING) pathway in orchestrating the bodys innate response to pathogenic, tumor or self-DNA in the cytoplasm has made it a hot target in immunology research and drug discovery, and several biopharma companies have started programs dedicated to that area, spanning infectious and inflammatory diseases as well as cancer. The second part of this feature examines the products undergoing preclinical development as well as the ones that are now in clinical testing.

Preclinical development

In June, Mersana Therapeutics Inc., of Cambridge, Mass., which is developing antibody-drug conjugate (ADC) therapies to treat cancer, closed a public offering of $174.8 million. In its pipeline it has Immunosynthen STING-agonist ADCs and, at the AACR 2020 virtual meeting, it presented preclinical data on multiple candidates that showed complete tumor regressions that were observed after a single dose. Those data also showed that the Immunosynthen STING-agonist ADCs were more active (over 100-fold increased potency) with significantly lower induction of systemic cytokines when compared to intravenously administered unconjugated (free) agonist, demonstrating the potential to confer an improved therapeutic index. In addition, potent ADC-mediated tumor regression led to durable immunological memory in an immune competent model. The company said selection of its first candidate remains on track for this year.

Codiak Biosciences Inc., of Cambridge, Mass., which is working on the development of exosome-based therapeutics targeting solid tumors, filed this month with the SEC to raise up to $100 million in an IPO. The company originally filed for an IPO in April 2019, aiming to raise $86 million, but withdrew it a few months later, citing market conditions.

One of the lead product candidates in the companys pipeline is exoSTING for the treatment of multiple solid tumors. Developed from its engex platform, the company explains that it is designed to selectively activate the STING pathway in tumor-resident antigen-presenting cells and attract and expand immune effector cells in the tumor microenvironment. Data from the companys preclinical studies suggest that, when administered intratumorally, the compound generates potent, targeted and systemic antitumor immunity without inflammatory cytokine-driven adverse events. A phase I/II trial in patients with a select group of solid tumors is being planned.

Boston-based Silicon Therapeutics Inc. reported at the annual AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics last year preclinical studies on its small-molecule, intravenously delivered STING agonist, SITX-799, demonstrating the compound produced robust and durable antitumor immunity and tumor regression.

In vivo studies showed that a single dose of SITX-799 produced complete regression of colon cancer tumors in mice and robust induction of type I interferons. Cured mice were re-challenged with tumors 90 days after initial treatment and remained tumor free, demonstrating durable, antitumor immunity. No antitumor response to treatment was observed in mice lacking a functional immune system, demonstrating the immune-therapeutic mechanism of action. SITX-799 was shown to be well-tolerated and demonstrated a favorable pharmacokinetic profile.

Onxeo SA, of Paris, said preclinical studies show OX-401, a PARP agonist, has strong antitumor activity and immunological properties. OX-401s antitumor activity was demonstrated in an animal model of breast cancer, related to PARP hyperactivation and diversion of its DNA repair function in specific tumor cells, the company said. The activity on PARP induces a strong engagement of the cGAS-STING pathway, as shown by the increase in key biomarkers of the tumor immune response, the company said. The next key preclinical milestone will be a study combining OX401 with immune checkpoint inhibitors.

In the clinic

In a research note, SVB Leerinks Daina Graybosch noted at the ongoing European Society for Medical Oncology (ESMO) virtual meeting, Merck & Co. Inc. reminded us that they are still interested in STING agonism, presenting a trial in progress poster for their phase II proof-of-concept trial in head and neck cancer.

The study is evaluating the efficacy and safety of intratumoral MK-1454, an investigational cyclic dinucleotide STING agonist, plus I.V. Keytruda (pembrolizumab) combination therapy vs. I.V. Keytruda anti-PD-1 antibody monotherapy as first-line treatment for metastatic or unresectable recurrent head and neck squamous cell carcinoma (HNSCC).

Cambridge, Mass.-based Synlogic Inc. is using synthetic biology to develop therapeutics. A paper published in Nature Communications highlighted the use for its engineered bacteria to target STING activation in tumors and activate innate immune pathways. The paper highlights preclinical data supporting its first clinical immuno-oncology program, SYNB-1891, which is being evaluated in a phase I trial in patients with advanced solid tumors or lymphoma. Data described in the publication demonstrate that SYNB-1891 treatment cleared tumors and stimulated antitumor immunity in preclinical models of cancer.

The product is an engineered strain of E. coli Nissle, that produces cyclic di-AMP, a stimulator of the STING pathway. Synlogic said it expects to release data from the monotherapy arm of this study late this year. After establishing a maximum tolerated dose as a monotherapy, a planned second arm of the study will involve subjects receiving escalating dose levels of SYNB-1891 in combination with a fixed dose of the checkpoint inhibitor Tecentriq (atezolizumab, Roche Holding AG) to establish a recommended dose for the combination regimen.

Noxopharm Ltd. is developing Veyonda, which has two main drug actions inhibition of sphingosine kinase and inhibition of STING signaling that provides an anti-inflammatory effect, also contributing to an anticancer action, but also potentially blocking sepsis.

It has recently begun a phase I Noxcovid-1 study in COVID-19 patients. The company believes the mechanism of action prevents the progression of the disease via the STING pathway into the cytokine storm leading onto septic shock. The study will involve approximately 40 patients and a range of doses of Veyonda will be administered to patients hospitalized with moderate symptoms who are at high risk of tipping over into a cytokine storm and developing septic shock.

One of the key endpoints is the effect of treatment on blood cytokine levels, and findings of the study are anticipated to be released in early-2021.

Venture capital

Ventus Therapeutics Inc. received $60 million from a series A funding to help leverage insights from its structural biology programs for inflammasome activation and cGAS-Sting signaling. The signal pathways underpinning those two sensory systems contain a significant number of validated drug targets that Ventus will be actively interrogating.

Actym Therapeutics Inc., of Berkeley, Calif., said it completed a $34 million series A financing led by Boehringer Ingelheim Venture Fund and Panacea Venture, with participation from Illumina Ventures, Korea Investment Partners and Jlo Ventures. The company will use the proceeds to advance development of immunotherapies from its microbial-based STACT (S. Typhimurium Attenuated Cancer Therapy) platform into the clinic for the treatment of various cancers, which includes a potentially first-in-class, systemically administered STING pathway agonist.

In May, Toronto-based Portage Biotech Inc. made an additional 900,000 (US$1.05 million) investment in its associate, Stimunity, a Paris-based cancer immunotherapy company focused on STING. The company had reached a significant milestone in its preclinical development plan and the additional financing will enable it to start the manufacturing of its biologic STING activating cGAMP- Virus-Like Particle (STI-001) lead compound.

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STING: A hot target in immunology research and drug discovery - BioWorld Online

Immunology

A Look Into The Immune System: Cornell Experts Explain How Our Bodies Fight Disease – Cornell University The Cornell Daily Sun

In the middle of a global pandemic, people now, more than ever, are invested in understanding how their immune system works.

Although many questions remain in the field of immunology research, The Sun interviewed three Cornell researchers to understand how the immune system functions when faced with an illness, and what experts recommend doing to assist the immune system in fighting off illness.

The immune system is always on the lookout for pathogens

Pathogens can enter the body in multiple ways, according to Prof. Cynthia Leifer, microbiology and immunology. These include the mouth and nose through either breathing in the pathogen or by touching your mouth, nose or eyes. Pathogens can also spread through eating something that contains pathogens or getting bit by a disease-carrying insect.

Whichever way pathogens enter the body, they will try to begin multiplying. According to Leifer, some bacteria can divide on their own, while viruses must hijack cells from the organism in order to reproduce.

Your body has basically a little army of cells that are constantly looking around for pathogens, and they have these little molecules on their surface called proteins that recognize the infectious agent, Leifer said.

The immune response has multiple components

Once a pathogen is detected, the first response is non-specific, focusing on limiting pathogen spread in ways that would impact any infectious agent rather than a specific bacteria, virus or other infectious agent.

There are events that happen very early on, and we call those innate mechanisms, Leifer wrote in a follow-up email. Those are just very rapid responses against an invading pathogen coming in, and these responses are relatively nonspecific.

According to lecturer Beth Rhoades, microbiology and immunology, the immune system includes T cells, which identify and kill infected cells, and macrophages, which dispose of the debris. There is also an adaptive response, which is largely driven by T cells and B cells cells that produce antibodies.

Antibodies are molecules that will tag a pathogen and say, eliminate this pathogen whatever is tagged with an antibody is in trouble, Rhoades said. The rest of the immune system will pick it up and destroy it one way or the other.

If the immune system has seen a pathogen before, it is better prepared to respond, according to Rhoades. Once B and T cells recognize a pathogen, they duplicate themselves, making what Leifer called a clonal army in order to fight that infection.

This memory response can be developed either by having the illness before, or through vaccination, which, unlike getting infected, is a safe way of developing a memory immune response.

It is often better to get a vaccine than to have a natural infection with a pathogen since vaccines are very safe and very effective, Leifer wrote.

Some pathogens cant stand the heat, but neither can people

A commonly misunderstood part of the immune system is fevers, a substantial rise in body temperature, which the immune system creates to fight off an illness.

The problem is that when youre talking about viruses, youre talking about millions and millions of them, said Prof. Hector Aguilar-Carreno, microbiology and immunology. When you raise the temperature, youre going to kill some of them, but not all of them.

According to Aguilar-Carreno, if a small number of viruses survive dehydration at high temperatures, these viruses can continue to reproduce. For this reason, while the fever response can help promote recovery, high temperatures alone do not guarantee that illnesses wont spread in or outside the body.

Fevers can not only dehydrate the pathogens infecting someone, but also the person. For this reason, medical professionals often work to alleviate the fever component of the immune response.

Too little of an immune response is bad, but so is too much

While too little of an immune response risks letting an infection progress, damaging tissues and endangering someones life, too strong of an immune response can also have repercussions. An overactive immune response can cause inflammation and tissue damage, according to Leifer.

You want the Goldilocks zone, where you have just the right immune response to kill the pathogen and not damage your own tissues, Leifer said.

COVID-19 exemplifies the need for staying within this zone as both the virus itself and the immune system response to it pose a risk. While the coronavirus is a threat, so is the inflammatory response it can provoke in the lungs and other organs, causing tissue damage, according to Leifer.

Strengthening the overall immune response is a complex task

While vaccines are well established as a safe way to develop immunity to specific pathogens, scientists are still working on finding out how to strengthen the immune system as a whole, and trying to understand what gives someone a stronger or weaker immune system.

According to Aguilar-Carreno, while researchers have determined that a balanced diet and exercise contributes to a healthy immune system, they are still working on determining mechanisms for why this is the case.

While many people may think that vitamin C and other supplements strengthen their immune system, Rhoades cautions against thinking that any one approach can make a perfect immune system.

There are all sorts of supplements that contribute to having a healthy immune system, but theres no magic bullet, Rhoades wrote in a follow-up email. The best thing that you can do is to get vaccinated, if you are able, and allow your body to set in place all of the layers of the immune response that you need.

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A Look Into The Immune System: Cornell Experts Explain How Our Bodies Fight Disease - Cornell University The Cornell Daily Sun

Immunology

COVID-19 may damage bone marrow immune cells; another reinfection reported – Reuters

(Reuters) - The following is a roundup of some of the latest scientific studies on the novel coronavirus and efforts to find treatments and vaccines for COVID-19, the illness caused by the virus.

FILE PHOTO: People walk past an illustration of a virus outside a regional science centre, as the city and surrounding areas face local restrictions in an effort to avoid a local lockdown being forced upon the region, amid the coronavirus disease (COVID-19) outbreak, in Oldham, Britain August 3, 2020. REUTERS/Phil Noble

COVID-19 may damage immune cells in the bone marrow

Even bone marrow may not be a safe harbor from the ravages of COVID-19, according to a study that found previously unrecognized changes in newly produced immune cells, called monocytes, released into the blood from bone marrow. To learn more about how the body responds to COVID-19, researchers obtained serial "snapshots" of patients' immune health by analyzing their immune cells at multiple points during their hospital stays. In COVID-19 patients with more severe disease, the monocytes do not function properly, researchers reported last week in Science Immunology. It was not yet clear whether the monocytes are being released from the bone marrow in an altered state or whether the alterations happen after monocytes enter the blood, coauthor Tracy Hussell of the University of Manchester in the UK told Reuters. Either way, she said, treatments that prevent their release from the bone marrow may help reduce the exaggerated immune response that contributes to poor outcomes in patients with severe COVID-19. (bit.ly/3mziJls)

COVID-19 reinfections occur, but remain rare

Another case of reinfection after recovery from COVID-19 has been reported, this time in a healthy young military healthcare provider at a U.S. Department of Defense hospital in Virginia. He was first infected by a patient in March. He recovered within 10 days and "returned ... to excellent health," his doctors reported on Saturday in Clinical Infectious Diseases. Fifty-one days later, he was reinfected by a household member. Genetic studies showed the first and second infections to be from slightly different strains of the virus. The reinfection made him sicker, perhaps because the second strain was more potent, or the household contact infected him with a higher load of virus, doctors said. It was also possible antibodies from the first infection may have triggered his immune system to respond more strongly to the virus the second time his body encountered it. COVID-19 reinfections are still rare, they said. Kristian Anderson, professor of immunology and microbiology at Scripps Research in La Jolla, California, recently told Reuters virus reinfections are always possible. "We don't know at what frequency reinfections (with the new coronavirus) occur and how that might change over time," Anderson said. Without further studies, "we can't conclude what a single case of reinfection means for longevity and robustness of COVID-19 immunity and relevance for a future vaccine," she added. (bit.ly/2Hln23P)

Proven immunotherapy approach might be possible in COVID-19

A proven approach to severe virus infections, known as cytotoxic T cell therapy, may be applicable to COVID-19 despite a potential hurdle, researchers said. The approach involves treating critically ill patients with infusions of key immune cells known as T-lymphocytes obtained from people who successfully fought off the same virus. These donor T cells have learned to recognize and target the invading virus. But steroids, which are being increasingly used to treat COVID-19 patients, are toxic to lymphocytes, likely canceling out any beneficial effects of the immunotherapy. In a new report posted on bioRxiv ahead of peer review, researchers describe a possible workaround. They say they have figured out a way to take donor T cells that target the novel coronavirus and make them resistant to the deadly effects of steroids. "We are currently working on ... developing clinical trials to determine safety and efficacy," coauthor Dr. Katy Rezvani of The University of Texas MD Anderson Cancer Center told Reuters. (bit.ly/3hNL83x)

High COVID-19 mortality seen in assisted-living facilities

Data compiled from more than 4,600 assisted living facilities in seven U.S. states through the end of May showed a four-fold higher COVID-19 fatality rate than in the nearby communities, researchers reported on Monday in the Journal of the American Geriatric Society. In North Carolina and Connecticut, for example, the proportions of COVID-19 cases that were fatal across the state were 3.3% and 9.3%, respectively. In assisted living facilities in those states, the fatality rate climbed to 13% and 31.6%. Unlike nursing homes, assisted living communities are not subject to federal regulation and are not required to collect and report data on COVID-19, coauthor Helena Temkin-Greener of the University of Rochester School of Medicine & Dentistry said in a news release. In this study, and in a separate study of nursing homes her team published on Monday in the same journal, COVID-19 cases were more common in facilities with more minority residents and more residents with dementia, chronic obstructive pulmonary disease, and obesity. "Assisted living communities and their residents urgently need local, state, and the federal governments to pay at least the same level of attention as that given to nursing homes," Temkin-Greener and colleagues conclude. (bit.ly/3iUaApI; bit.ly/3cjjVEN)

Open tmsnrt.rs/3a5EyDh in an external browser for a Reuters graphic on vaccines and treatments in development.

Reporting by Nancy Lapid and Deena Beasley; Editing by Bill Berkrot

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COVID-19 may damage bone marrow immune cells; another reinfection reported - Reuters

Immunology

Childrens Immune Response Protects Them Against COVID-19 According to New Study – Technology Networks

The first study comparing the immune responses of adults and children with COVID-19 has detected key differences that may contribute to understanding why children usually have milder disease than adults. The findings also have important implications for vaccines and drugs being developed to curb COVID-19. The study was published today inScience Translational Medicineand was conducted by scientists atAlbert Einstein College of Medicine,Children's Hospital at Montefiore(CHAM), and Yale University.

The study involved 60 adult COVID-19 patients and 65 pediatric COVID-19 patients (less than 24 years old) hospitalized at CHAM andMontefiore Health Systembetween March 13 and May 17, 2020; 20 of the pediatric patients had the novel multi-system inflammatory syndrome (MIS-C). The patients' blood was tested for the presence of several types of immune cells, antibody responses, and the inflammatory proteins, known as cytokines, that immune cells produce.

Children with COVID-19 fared significantly better than adults. Twenty-two adults (37%) required mechanical ventilation compared with only five (8%) of the pediatric patients. In addition, 17 adults (28%) died in the hospital compared with two (3%) of the pediatric patients. No deaths occurred among pediatric patients with MIS-C.

"Our findings suggest that children with COVID-19 do better than adults because their stronger innate immunity protects them against SARS-CoV-2, the novel coronavirus that causes the disease," said co-senior authorBetsy Herold, M.D., chief of infectious diseases and vice chair for research in the department of pediatrics at Einstein and CHAM.Kevan C. Herold, M.D., C.N.H. Long Professor of Immunology and of Medicine atYale School of Medicine, was the other co-senior author on the study.

People have two types of immunity--innate and adaptive. Innate immunity, in which immune cells respond rapidly to invading pathogens of all kinds, is more robust during childhood. Adaptive immunity, the second type of immune response, is more specific and features antibodies and immune cells that target specific viruses or other microbes.

Compared with adult patients, pediatric COVID-19 patients in the study possessed significantly higher levels of certain cytokines associated with the innate immune response. This suggests that young people's more robust innate response protects them from developing acute respiratory distress syndrome (ARDS)--the hallmark of severe and often fatal COVID-19 cases. One cytokine in particular, known as IL-17A, was found at much higher levels in pediatric patients than in adults. "The high levels of IL-17A that we found in pediatric patients may be important in protecting them against progression of their COVID-19," said Dr. K. Herold.

Both pediatric and adult COVID-19 patients were found to make antibodies against the coronavirus' spike protein, which the virus uses to latch onto and infect cells. Those spike-protein antibodies include neutralizing antibodies, which block the coronavirus from infecting cells. Counterintuitively, the researchers found that neutralizing antibody levels in adult COVID-19 patients who died or required mechanical ventilation were higher than in those who recovered--and significantly higher than levels detected in pediatric patients.

"These results suggest that the more severe COVID-19 disease seen in adults is not caused by a failure of their adaptive immunity to mount T-cell or antibody responses," said Dr. K. Herold. "Rather, adult patients respond to coronavirus infection with an over-vigorous adaptive immune response that may promote the inflammation associated with ARDS."

The findings have important implications for COVID-19 therapies and vaccines. "Our adult COVID-19 patients who fared poorly had high levels of neutralizing antibodies, suggesting that convalescent plasma--which is rich in neutralizing antibodies--may not help adults who have already developed signs of ARDS," said Dr. B. Herold. "By contrast, therapies that boost innate immune responses early in the course of the disease may be especially beneficial."

As for vaccines, Dr. B. Herold notes that most vaccine candidates for protecting against SARS-CoV-2 infection are aimed at boosting neutralizing-antibody levels. "We may want to consider assessing vaccines that promote immunity in other ways, such as by bolstering the innate immune response," she said.

Reference: Pierce CA, Preston-Hurlburt P, Dai Y, et al.Immune responses to SARS-CoV-2 infection in hospitalized pediatric and adult patients.Sci. Transl. Med.2020;eabd5487 doi:10.1126/scitranslmed.abd5487

This article has been republished from the following materials. Note: material may have been edited for length and content. For further information, please contact the cited source.

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Childrens Immune Response Protects Them Against COVID-19 According to New Study - Technology Networks

Immunology

OPEN Health’s Learning & Development team have won a Bronze Award at the PM Society Digital Awards 2020 – PMLiVE

READ MORE ABOUT OUR WINNING PROJECT WITHWITH JANSSEN BELOW:

The Immunology Training Summit (ITS) 2020 with theJanssen EMEA Immunology team took a week-long face-to-face meeting for 120 attendees and transformed it into a 3.5 day-long virtual meeting for 250 attendees in record time due to the unprecedented challenge of COVID-19. By embracing the right technology, digital tools, and innovative approaches, high engagement was maintained and 97% of attendees agreed that ITS2020 achieved its objectives of driving knowledge, competence and confidence of the medical team to deliver on strategy during crucial launch and pre-launch phases. This annual training was fundamental to ensure that the teams were equipped to develop skills and expertise that enable them to be responsive to the needs of HCPs and ultimately improve patient outcomes. Strikingly this format is now considered best practice in internal training at Janssen.

About OPEN Health

OPEN Health is a family of expert practices working in partnership to drive positive change in healthcare communications and market access globally. It all started with a vision for improving the lives of patients, worldwide. The OPEN Health vision has come alive with the integration of experts from Pharmerit and Peloton Advantage to create a new unique entity equipped to be a global leader in HEOR, market access, medical and patient brand communications and digital services.

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OPEN Health's Learning & Development team have won a Bronze Award at the PM Society Digital Awards 2020 - PMLiVE