Category Archives: Immunology

Genetically engineered animals offer fresh hope to heart valve patients – ScienceBlog.com

Every year, about 300,000 people worldwide receive a new heart valve. Whenever possible, doctors use valves made of tissue from cows or pigs, because the synthetic alternatives can cause blood clots.

But there is a hitch. Although animal tissue valves can last up to 30 years in people over 60 years old, they can be destroyed in just five years in a younger person, probably because of their more aggressive immune system.

Enter the genetically engineered bull.

Scientists used CRISPR gene editing technology to create two bovine mutations that should lessen peoples immune responses to the animal tissue.

The mutations knock out two sugars which coat the bulls cells but are not found in humans: -Gal and Neu5Gc.

The objective is to have animals that express tissues that are less foreign to the human body, said Dr Emanuele Cozzi, coordinator of a project calledTRANSLINK, which has been trying to improve the long-term success of heart valve replacements.

In theory this means peoples immune systems will be less likely to attack the animal tissue, added Dr Cozzi, who is director of the Transplant Immunology Unit at Padua University Hospital in Italy.

Clone

As part the project, an Italian company,Avantea, created bovine cells with the two mutations and used them to clone a bull with a technique similar to the one that producedDolly the sheep.

We are the first to make cattle (with these) mutations, said Professor Cesare Galli, co-founder of Avantea.

The cloning step is required to make the founder animals. Then they can breed normally, said Prof. Galli.

Avantea had created the same mutations in pig cells using a technology called Transcription activator-like effector nucleases (TALEN) to edit the DNA, before CRISPR was available.

With CRISPR it is much easier to prepare the reagents that are needed to implement the system, said Prof. Galli.

That makes CRISPR cheaper because the reagents can be prepared in-house. However, in theory at least, it is less accurate, he added.Being less precise in recognising the sequence to cut, there is the risk of undesired cuts this is a risk that has yet to be quantified.

The animals we generated could have a potential application for food consumption, at least for people who do not tolerate red meat.

Professor Cesare Galli, co-founder, Avantea, Italy

Quality of life

About 100,000 people a year are given synthetic heart valves because they are too young to receive the animal tissue version.

But these valves can lead to dangerous blood clots forming, so patients have to live on anticoagulants that impose severe limitations on a young persons life, saysDr Cozzi.

People have to avoid competitive sports and jobs with a high risk of injury, like construction or some police work.

If an accident occurs while on duty (they) may bleed to death, said Dr Cozzi.

Although preliminary data suggests that peoples immune systems attack valve transplants in response to the animal tissue used, scientists need more solid evidence of this before they can recommend using the genetically engineered animal tissue, says Dr Cozzi.

Other factors including someones blood pressure cannot yet be ruled out as affecting the valves lifespan, he says.

To understand more, TRANSLINK is carrying out a study of 1,600 cardiac patients the largest of its kind to compare their immune responses to animal or synthetic valve transplants or other types of surgery. The results are expected next year.

If the study shows convincingly that immunology is behind the premature failure of animal-derived heart valves, it should not be too difficult to find potential investors who could bring the genetically engineered tissue valves to market, says Dr Cozzi.

My hope would be that, based on the data of our study, we may change the outlook of young patients (and offer them) a better quality of life.

The mutations in both pigs and cows may pave the way for people to receive transplants of whole animal organs, Dr Cozzi says.

Red meat allergies

The cloned animals may also benefit people allergic to red meat a reaction which sometimes develops after they have been bitten by a tick.

Scientists think the main culprit is the -Gal sugar found in all animals other than primates.

Anything from a steak to collagen used in cosmetics can trigger a reaction, which can range from a skin rash to anaphylactic shock.

The animals we generated could have a potential application for food consumption, at least for people who do not tolerate red meat, said Prof. Galli.

Some scientists in the US are also looking at possible links between the Neu5Gc sugar and cancer. The World Health Organization has classified red meat asprobably carcinogenic to humans,although there is limited evidence.

Millions of years ago, humans developed a mutation that stopped the production of Neu5Gc and produced a slightly different sugar called Neu5Ac instead. The mutation made people resistant to malaria, and quickly spread across the population.

Pigs, sheep, cows and most other mammals with the exception of deer and some dogs produce the Gc form which is highly antigenic in humans, says Prof. Galli, meaning it prompts a strong immune response.

Chicken and fish do not, which is one reason they are considered to be healthier to eat.

The cloned cows could be a useful source of milk for baby food, as it would be closer to human milk because it does not carry the antigen, says Prof. Galli.

Avantea also plans to use CRISPR to create horses with the same mutations as the cows and pigs. Horse serum is used to make antidotes to snake bites, but it can trigger adverse reactions in some people. Knocking out -Gal and Neu5Gc may prevent that, he says.

The potential for the cloned pigs, cows and horses to improve peoples health is huge. But for the time being, much of it is still theory, the scientists say.

We have the tools now, but there is work to be done to prove whether there is an advantage or not, said Prof. Galli.

The research in this article was funded by the EU. If you liked this article, please consider sharing it on social media.

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Genetically engineered animals offer fresh hope to heart valve patients - ScienceBlog.com

These overlooked global diseases take a turn under the microscope – Penn: Office of University Communications

Most people dont die from tropical diseases like hookworm, schistosomiasis, or even malaria. But these understudied diseases, often caused by parasites, rob people of health in sometimes insidious ways.

For example, schistosomiasis is a disease caused by a waterborne, snail-transmitted parasite, and its the research focus of the School of Veterinary Medicines Robert Greenberg.

Its not necessarily a death sentence, though there are fatalities says Greenberg, a research associate professor of pathobiology. But you get anemia, children get stunted in terms of growth and cognitive abilities. Its a disease that keeps people in poverty.

Such diseases, by and large, receive less financial support and, as a result, far less scientific attention than those that more often afflict residents of wealthier nations, such as diabetes and heart disease.

Penn Vet researchers, however, have committed attention to these diseases, which, taken as a whole, affect billions around the globe. Their work benefits from the niche strengths of the school, specifically in immunology and host-pathogen interactions.

At the Vet School, a third of our funding supports infectious disease research, says Phillip Scott, vice dean for research and academic resources and a professor of microbiology and immunology in the Department of Pathobiology. Thats pretty amazing, given that the School is also awarded funding for regenerative medicine, for cancer, and for a variety of other areas.

That strength is seen in the research portfolios of some of the more senior faculty, such as Christopher Hunters work on toxoplasmosis, James Sparky Loks studies of Strongyloides, Carolina Lopezs investigations of lung infections, and Bruce Freedman and Ron Hartys efforts against Ebola and other hemorrhagic viral diseases. It has attracted newer faculty members, like cryptosporidium expert Boris Striepen, to Penn Vet.

Penn VetsDeBroski Herbert, for example, an associate professor of pathobiology, had held prior positions at Cincinnati Childrens Hospital and the University of California, San Francisco. He had felt called to work on hookworm, a parasite he first learned of growing up in the South from his great-grandmother, who warned him about walking around barefoot because of the risk of contracting the parasite. But at the medical centers where he worked, he shifted gears away from studying the parasite itself, instead focusing on related research in asthma and allergy.

Here, our veterinary students are likely to encounter parasites in their patients, so working directly on the parasite is easier to justify, Herbert says.

This spring, Herbert traveled to Nigeria where, working with partners at the Nigerian Institute for Medical Research, he launched a study of hookworm in 300 school-aged children in five sites around the northern and central portions of the country.

The goal is to first establish what the prevalence of the disease really is and draw attention to that, Herbert says. And secondly, this is a place where the World Health Organization is going in and doing mass treatments, so Im also interested in learning something very novel about the association between the microbiome, tissue repair, immune suppression, and metabolism in these children in Nigeria.

Those insights could lead to treatments, but they will also likely shed new light on the basic science of how hookworms affect their host. This pairing of basic and applied work is characteristic of Penn Vet scientists. In Scotts lab, for instance, which has long pursued studies of the tropical disease leishmaniasis, advances in basic science have unfurled alongside insights that stand to reshape treatment of this parasitic infection which, in its cutaneous form, can cause serious and chronic skin ulcers.

When I was a postdoc at NIH, theres something my boss used to say that I still use in my talks, says Scott. He said, Leishmaniasis has done more for immunology than immunology has done for leishmaniasis. And you could substitute parasitology for leishmaniasis and it would be much the same quote.

What I think is exciting right now, he adds, is that thats going to change.

As part of this contribution toward advancements against parasitic disease, Scott has traveled regularly to a leishmaniasis clinic in Brazil to obtain samples for his research and, back at Penn, has paired up with dermatology and microbiome experts such as Elizabeth Grice in the Perelman School of Medicine, and Dan Beiting from Penn Vets Center for Host-Microbial Interactions to break new ground.

No vaccine exists for leishmaniasis and current therapies fail a substantial percentage of the time. But recent publications from Scotts lab have revealed new information about how the disease and existing treatments work and when to predict when they dont. At the same time, Scott and colleagues research into the immunology of the infection has identified ways that FDA-approved drugs could be leveraged to alleviate the most severe forms of leishmaniasis.

A major hurdle to matching appropriate therapies with neglected disease comes at one of the earliest stages of medical intervention: diagnostics. Researchers at Penn Vet are employing innovative techniques to fill these unmet needs. Robert Greenberg is one who has crossed disciplinary boundaries to do so.

In a partnership between Greenberg and Haim Bau of Penns School of Engineering and Applied Science, the scientists are working to craft an improved diagnostic test for schistosomes, which can lead to schistosomiasis, causing anemia, tissue fibrosis and lesions, malnutrition, learning difficulties, and, depending on the parasite species, bladder cancer and heightened HIV risk.

Greenberg has studied the ion channels that govern key biological functions in schistosomes to potentially develop drug targets that paralyze and kill the organisms. And by adapting insights from other researchers about additional parasitic-specific targets, he's helping Bau train hismicrofluidic, portable diagnostic system on schistosomes to one day help clinicians make point-of-care diagnoses and issue timely treatment for infected patients.

The current diagnostics are pretty terrible, Greenberg says. Were looking at some new approaches now that should give us a much earlier, more sensitive, and more specific diagnosis for individual patients that might be able to detect other coinfections simultaneously.

At Penn Vets New Bolton Center, Marie-Eve Fecteau and Ray Sweeney are also taking part in the design of a 21st-century solution to diagnostics of an insidious and challenging disease, in this case, a disease that takes a particular toll on livestock: paratuberculosis, or Johnes disease. Caused by the bacterium Mycobacterium avium paratuberculosis, the condition affects ruminants such as cows and goats and drastically decreases their weight and milk production.

Ruminants are a very important part of survival and livelihood in developing countries, says Fecteau, an associate professor of food animal medicine and surgery. Families may rely on only one or two cows to provide for their nutritional needs or income, and if that cow is affected by Johnes, thats a serious problem.

Paratuberculosis has been shown to be endemic in parts of India and elsewhere in Asia and is also a burden for U.S. farms, where 70% of dairy herds test positive for the infection. Separating infected animals from the herd is a key step to stem the spread, but the bacteria have proved difficult to grow in the lab, making diagnosis challenging.

Fecteau and Sweeney, the Mark Whittier & Lila Griswold Allam Professor at Penn Vet, are hoping to change that, working with Beiting and biotechnology firm Biomeme to develop a lab in a fanny pack, as they call it: A stall-side diagnostic test that relies on PCR to identify infected animals from stool samples within hours.

This is the kind of technology that could be extremely valuable for use in areas where sophisticated technology is harder to come by, says Sweeney.

Elsewhere at Penn Vet, researchers are approaching globally significant diseases by focusing on the vector. In the insectary that is part of Michael Poveloness lab, he and his team test methods to stop disease-transmission cycles within mosquitoes.

In the work, which relies on disrupting the way that mosquitoes interact with or respond immunologically to the pathogens they pass on, Povelones, an assistant professor of pathobiology, has explored everything from dengue to Zika to heart worm to elephantiasis, and his discoveries have implications for targeting a much longer list of diseases. In a recent study, Povelones and colleagues developed a new model system for studying the transmission of diseases caused by kinetoplastids, a group of parasites that includes the causative agents of Chagas disease and leishmaniasis.

We think this could be a model for a number of important neglected diseases, Povelones says.

In the latest of his teams work finding ways to activate mosquitoes immune system to prevent pathogen transmission, theyve identified a strategy that both blocks heartworm and the parasite that causes elephantiasis.

These two diseases have very different behavior once theyre in the mosquito, so were still figuring out why this seems to work for both, says Povelones. But were very encouraged that it does.

Using these types of creative approaches is a common thread across the Vet School, and the researchers efforts and successes seem to be multiplying. To continue accelerating progress, the School is developing a plan to harness these strengths, working with existing entities such as the Center for Host-Microbial Interactions internally and cross-school units such as the Institute for Immunology.

We are a key part of the biomedical community at Penn and bring a valuable veterinary component to the table in confronting diseases of poverty, says Scott.

Homepage image: Bruce Freedman and Ronald Harty of the School of Veterinary Medicine have used a non-infectious model to study how the Ebola virus spreads from cell to cell. Their findings have pointed to new targets for a drug to reduce the severity of Ebola infection. (Image: Gordon Ruthel/Penn Vet)

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These overlooked global diseases take a turn under the microscope - Penn: Office of University Communications

Infectious Immunology Market 2019, Trend, CAGR Status, Growth, Analysis and Forecast to 2025 – VaporBlash

The upcoming market report contains data for the historical year 2015, the base year of calculation is 2016 and the forecast period is 2017 to 2024. The https://marketreports.co/global-infectious-immunology-market-size-status-and-forecast-2019-2025/171459/#Free-Sample-Report

The report offers information of the market segmentation by type, application, and regions in general. The report highlights the development policies and plans, government regulations, manufacturing processes, and cost structures. It also covers technical data, manufacturing plants analysis, and raw material sources analysis as well as explains which product has the highest penetration, their profit margins, and R&D status.

Read Detailed Index of full Research Study at @ https://marketreports.co/global-infectious-immunology-market-size-status-and-forecast-2019-2025/171459/

The Top Key players Of Global Infectious Immunology Market:

Types of Global Infectious Immunology Market:

Applications Of Global Infectious Immunology Market:

Regional Segmentation for Infectious Immunology market:

Table of Content (TOC) at a glance:Overview of the market includes Definition, Specifications, and Classification of Infectious Immunology Size, Features, Scope, and Applications.

Product Cost and Pricing Analysis: The Manufacturing Cost Structure, Raw Material, and Suppliers cost, Manufacturing Process, Industry Chain Structure.

Market Demand and Supply Analysis that includes, Capacity and Commercial Production Date, Manufacturing Plants Distribution, R&D Status and Technology Source, Raw Materials Sources Analysis;Forces that drive the market

In the end, the report covers the precisely studied and evaluated data of the global market players and their scope in the market using a number of analytical tools. The analytical tools such as investment return analysis, SWOT analysis, and feasibility study are used to analyses the key global market players growth in the Infectious Immunology.

Check here for the [emailprotected]https://marketreports.co/global-infectious-immunology-market-size-status-and-forecast-2019-2025/171459/#Buying-Enquiry

Customization of the Report:This report can be customized to meet the clients requirements. Please connect with our sales team ([emailprotected]), who will ensure that you get a report that suits your needs.

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Detecting Potential Anticancer Compounds That Reawaken T Cells – Technology Networks

Scientists at Scripps Research have developed a method for rapidly discovering potential cancer-treating compounds that work by resurrecting anti-tumor activity in immune cells called T cells.

Cancerous tumors often thrive because they render T cells dysfunctional or exhausted. The new method uncovers medicinal compounds that can restore the function of these T cells, making cancers vulnerable to them again.

The approach, described in a studypublished inCell Reports, may also help restore T-cell responses to persistent infections from viruses or other pathogens. It therefore should speed the development of new cancer and infectious-disease immunotherapies, including those that can be combined with existing immunotherapy drugs to enhance their effects. The scientists demonstrated the potential utility of the approach by using it to rapidly screen a collection of more than 12,000 drug compoundsuncovering 19 that can reawaken exhausted T cells.

This new screening method should be particularly useful because we can use it not only to identify compounds that restore needed function to exhausted T cells, but also to quickly analyze these T cells to determine how these compounds work on them, says senior authorMichael Oldstone, MD, Professor Emeritus in the Department of Immunology and Microbiology at Scripps Research.

The new screening systemand to some extent, the wider field of cancer immunotherapyis based in part on research over the past several decades by Oldstones laboratory and several former lab members including Rafi Ahmed, David Brooks, and John Teijaro, along with other scientists that have conducted animal-based research on how the immune system responds to lymphocytic choriomeningitis virus (LCMV).

A unique variant of LCMV known as clone 13 establishes a persistent infection by exhausting the virus-specific T cells that are required to clear the infection. It does this by boosting signals through T-cell receptors such as PD-1 and IL-10. The discovery that LCMV clone 13 can survive by switching off anti-LCMV T cells was quickly followed by the recognition that cancers often persist using the same trick.

Immunotherapies that block signaling from PD-1 or similarly acting receptors to restore T cells anti-cancer responses are among the most powerful cancer medicines available today. These therapies save many patients who in the past had seemingly untreatable tumors. But because treatment with these drugs typically works well for only a few cancers, including melanomaand less often on other cancersscientists suspect that cancers usually hijack multiple inhibitory T-cell pathways. This suggests that a combination of immunotherapies directed to different molecular pathways could be more effective than the current therapy.

The idea now is to develop more immunotherapy drugs and find the best combinations of them, Oldstone says.

A promising hit

The new screening system is designed to enable scientists to swiftly find such drugsin this case, pharmacologically active small-molecule compounds that might work better than, or augment, the current injectable antibody immunotherapies now available.

The system uses T cells that have been exhausted by LCMV clone 13 and detects signs of renewed activity in these cells when a tested compound works to reawaken them. An advantage of the new screening system is that it is specific and highly automated; thus, thousands of compounds can be tested within days, with the hits verified in experiments involving mice.

Oldstone and colleagues applied the new screening system to adrug repurposing libraryof more than 12,000 compounds that either are FDA-approved or have been tested as potential drugs. They quickly identified 19 hitscompounds that, at modest doses, can effectively resurrect the activity of exhausted T cells.

One of these compounds, ingenol mebutate, is a plant-derived molecule that is already used in gel form (Picato) to treat actinic keratosis, a pre-cancerous skin condition. The researchers employed elements of their screening system to study the reactivated T cells and determined that ingenol mebutate restores function for these cells largely by activating signaling enzymes called protein kinase C enzymes, a known pathway of activity for this compound.

Co-first authors of the study, postdoctoral fellows Brett Marro, PhD and Jaroslav Zak, PhD, in the Department of Immunology and Microbiology, are currently collecting and exploring the therapeutic potential of other reported hits that may work in combination with treatments that block PD-1- and another T-cell-inhibitory receptor, CTLA-4. Indeed, one such hit in combination with antibody to PD-L1 is already undergoing evaluation in patients.

Oldstone notes that the new screening approach is flexible enough to adapt for finding compounds that have other effects on T-cells, such as reducing T-cell activity to treat autoimmune conditions.

Reference: Marro, et al. (2019) Discovery of Small Molecules for the Reversal of T Cell Exhaustion. Cell Reports. DOI:https://doi.org/10.1016/j.celrep.2019.10.119

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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Aqilion strengthens its portfolio with two innovative pharmaceutical projects in the fields of inflammation and oncology – PharmiWeb.com

Aqilion is strengthening its portfolio with the addition of two innovative preclinical projects, Alhena and Alnitak. The company is overseeing the two pharmaceutical projects, which both fall under Aqilions new focus area: inflammation at the interface of oncology and immunology.

The Alhena project aims to develop a PROTAC drug against a target protein that is central to some cancers. PROTAC is an acronym for proteolysis-targeting chimera (PROTAC). Basically, the technology uses the cells own system to break down a certain target protein in the cell, instead of just trying to block its action. The Alhena project involves combination therapy in immuno-oncology with an initial focus on aggressive, treatment-resistant triple negative breast cancer.

The Alnitak project has two interesting applications. The goal is to develop drug candidates that bind to a target protein that is essential for both malignant disease development and for inflammatory conditions. A successful project can therefore help to develop new medications to treat orphan drug indications in the field of autoinflammatory diseases, as well as new combination therapies within the field of oncology, primarily intestinal cancer.

Aqilion oversees both projects in collaboration with selected contract research organizations (CROs) specializing in innovative early pharmaceutical projects. The objective is to develop both projects into attractive preclinical projects and then identify a partner for the clinical and commercial development.

We are proud to announce that Aqilion is now launching two innovative pharmaceutical projects that are both based on new knowledge from the pharmaceutical industry and academic research in the fields of oncology, inflammation and immunology. I am convinced that our new area of focus and approach will result in synergies, greater knowledge within the team and strong collaboration in the future with selected partners and customers in industry. I look forward to reporting the results moving forward, says Sarah Fredriksson, CEO of AQILION AB.

Aqilion is in a transitional phase that has entailed a new start based on solid analysis and culminating in a forward-looking strategy. Earlier this year, the company changed its name to Aqilion in acknowledgement of this transition. The path has included recruitment of a strengthened team, as well as an inventory and validation of the projects Aqilion had in its portfolio at that time. Willingness to build a business model that delivers, combined with the courage to discontinue those projects that do not meet set criteria, will be crucial to its success.

For more information, please contactSarah Fredriksson, CEO, AQILION AB, +46 (0)70 261 4575, sarah.fredriksson@aqilion.com

About AQILION ABAqilion is a Swedish life science company that identifies unique pharmaceutical projects at an early phase in the drug discovery process and develops them in preparation for clinical trials. The goal is to demonstrate the clinical and commercial potential of the medical innovation to attract industrial partners and buyers, who in turn have the capacity to continue clinical development and take the product to market. The business model is based on involvement at an early stage and close collaboration with the innovator, regardless of whether the project is initiated by an external researcher, internal development project, or industrial partner. Aqilion prefers projects aimed at niche markets. Specialty medications and orphan drugs are of particular interest. Aqilion has its headquarters in Helsingborg. Please visit http://www.aqilion.com.

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Aqilion strengthens its portfolio with two innovative pharmaceutical projects in the fields of inflammation and oncology - PharmiWeb.com

RAPT Therapeutics Appoints Rodney Young as Chief Financial Officer – BioSpace

SOUTH SAN FRANCISCO, Calif., Dec. 04, 2019 (GLOBE NEWSWIRE) -- RAPT Therapeutics, Inc. (Nasdaq: RAPT), a clinical-stage immunology-based biopharmaceutical companyfocused on discovering, developing and commercializing oral small molecule therapies for patients with significant unmet needs in oncology and inflammatory diseases, today announced the appointment of Rodney Young as chief financial officer effective December 2, 2019.

As a newly public company, we are thrilled to welcome Rodney to RAPT, said Brian Wong, M.D., Ph.D., president and CEO of RAPT Therapeutics. He is a seasoned executive who brings broad strategic, operational and financial expertise to help biotech companies grow successfully. Rodney will lead our finance and administrative functions and work closely with the executive team to guide the companys development across all operational areas.

Mr. Young brings more than 30 years of executive management and corporate finance experience. Most recently, he served as chief financial officer of Cellerant Therapeutics, Inc., a private clinical-stage company developing cell and antibody-based immunotherapies for blood cancers and related disorders, where he was responsible for accounting and financial management, and played a key role in determining corporate strategy. Previously, he served as chief financial officer and vice president of finance and administration of StemCells, Inc., a public biotechnology company developing stem cell therapeutics for central nervous system disorders, where he was responsible for raising over $200 million in financing. Earlier in his career, he was an investment banker at Lehman Brothers and SG Cowen, leading financing and merger and acquisition transactions focused in the healthcare, biotechnology, and pharmaceutical sectors. Mr. Young received his MBA and BA from the University of Chicago.

RAPT has a compelling drug discovery platform that has generated promising therapeutic drug candidates, said Mr. Young. With an experienced team and thoughtful clinical development plans, RAPT expects to have data from two compounds reading out in 2020. Im thrilled to join the company at this important time.

About RAPT Therapeutics, Inc.

RAPT Therapeutics (formerly FLX Bio) is a clinical stage immunology-based biopharmaceutical company focused on discovering, developing and commercializing oral small molecule therapies for patients with significant unmet needs in oncology and inflammatory diseases. Utilizing its proprietary discovery and development engine, the company is developing highly selective small molecules designed to modulate the critical immune responses underlying these diseases. In its first four years since inception, RAPT has discovered and advanced two unique drug candidates, each targeting C-C motif chemokine receptor 4. The companys lead oncology drug candidate, FLX475, reached the clinic in just two and a half years and RPT193, its lead inflammation drug candidate, is also in the clinic. The company is also pursuing a range of targets, including general control nonderepressible 2 and hematopoietic progenitor kinase 1, that are in the discovery stage of development.

Media Contact:Angela Bittingmedia@rapt.com(925) 202-6211

Investor Contact:Sylvia Wheelerswheeler@wheelhouselsa.com

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RAPT Therapeutics Appoints Rodney Young as Chief Financial Officer - BioSpace

Assessing Drug-Induced Anaphylaxis – Physician’s Weekly

Research indicates that approximately 1 in 3,000 hospitalized patients suffer drug-induced anaphylaxis. Previous studies investigating anaphylaxis epidemiology used billing codes to broadly determine causes of these life-threatening allergic reactions (eg, drug, food, and venom) but lacked information on specific causative drugs or drug classes. Large-scale studies using EHR allergy lists to describe drug allergy have been infrequent.

At Partners Healthcare System, patient allergy information captured by the EHR allergy module was integrated into the Partners enterprise-wide allergy repository (PEAR), resulting in a longitudinal allergy record accessible across the healthcare network. For a study published in The Journal of Allergy and Clinical Immunology: In Practice, my colleagues and I used drug allergy data of patients who visited Brigham and Womens Hospital and Massachusetts General Hospital between 1995 and 2013 to determine the population prevalence of anaphylaxis, including anaphylaxis prevalence over time and the most commonly implicated drugs/drug classes reported to cause anaphylaxis.

Among approximately 1.8 million patients, 1.1% reported drug-induced anaphylaxis. Penicillins (45.9 per 10,000), sulfonamide antibiotics (15.1 per 10,000), and NSAIDs (13.0 per 10,000) were most commonly implicated. Female gender, Caucasian race, systemic mastocytosis, Sjgrens syndrome, asthma, and COPD were risk factors for anaphylaxis. We found that serum tryptase was tested in less than 1% of anaphylaxis cases at any time (33% of tests ordered during the correct time window), and only 8% visited an allergist for follow-up during the study period (1.4% within 30 days of anaphylaxis).

The patient-specific risk factors noted above can be used clinically in discussion with patients about drug-induced anaphylaxis. Our findings also emphasize the need to improve the verification of EHR-reported anaphylaxis with tryptase testing and subsequent allergist evaluation.

Drug-Induced Anaphylaxis Documented in Electronic Health Recordshttps://www.jaci-inpractice.org/article/S2213-2198(18)30411-2/abstract

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Assessing Drug-Induced Anaphylaxis - Physician's Weekly

Phathom Pharmaceuticals Expands Leadership Team and Announces Board Transition – Business Wire

BUFFALO GROVE, Ill.--(BUSINESS WIRE)--Phathom Pharmaceuticals, Inc. (Nasdaq: PHAT), a late clinical-stage biopharmaceutical company focused on developing and commercializing novel treatments for gastrointestinal diseases, announced today multiple executive appointments. As previously announced as part of the Companys succession plan, Terrie Curran, former President of the Global Inflammation and Immunology (I&I) Franchise at Celgene, now joins Phathom as Chief Executive Officer. Founding CEO David Socks transitions to interim Chief Financial Officer and remains a member of the Board of Directors. In addition to Ms. Curran, also joining the Phathom leadership team are Eckhard Leifke, MD, as Chief Medical Officer; Joseph Hand, JD, as Chief Administrative Officer; and Larry Miller, JD, as General Counsel. Phathom also announced today that Asit Parikh, MD, PhD has replaced Chris Slavinsky on the Companys Board of Directors.

I am thrilled to be joining Phathom at this exciting time, as vonoprazan, our product candidate for the treatment of acid-related disorders, moves into Phase 3 clinical trials in multiple indications, said Ms. Curran. I look forward to continuing to work with David, along with our expanded leadership team, to bring this important and novel therapy to underserved patients. I am also very pleased with our ability to attract exceptionally talented and experienced leaders such as Eckhard, Joe, and Larry as we continue to build the Company.

Ms. Curran has more than 20 years of experience in the biopharmaceutical industry. She has served as President, Global Inflammation and Immunology (I&I) Franchise and as a member of the Executive Committee at Celgene Corporation since 2017. Ms. Curran joined Celgene in 2013 as the U.S. Commercial Head of the I&I Franchise and built the capabilities and recruited the teams that executed the successful launch of OTEZLA, which was sold to Amgen in November 2019 for $13.4 billion. Prior to joining Celgene, she served as Senior Vice President and General Manager, Global Womens Health at Merck & Co. She currently serves on the board of Myovant Sciences and previously served on the board of H. Lundbeck A/S. Ms. Curran holds graduate and bachelors degrees from the University of Technology, Sydney.

Dr. Leifke joins Phathom from Omeros where he served as Chief Medical Officer. Prior to Omeros, he held executive roles at Sanofi, including Global Head/Vice President of Early Project & External Opportunities - Cardiovascular and Metabolism and Global Head/Vice President of Late Stage Development - Diabetes. Dr. Leifke has built global teams at pharmaceutical companies including Bayer and Takeda and led the global development of multiple early- and late-stage small molecule and biologic drug candidates to successful marketing authorizations worldwide. Dr. Leifke holds an MD from the University of Freiburg, Germany and is board-certified in internal medicine and endocrinology.

Mr. Hand joins Phathom from Celgene, where he most recently served as Executive Vice President, Global Human Resources and Corporate Services and a member of its Executive Committee. In that capacity, he was responsible for all employee-related activities including talent development, recruiting, and compensation and benefits. He was also responsible for the management of Celgenes global facilities footprint. Prior to Celgene, he was a litigation attorney at the international law firm of Jones Day. Mr. Hand holds a BBA from the University of Notre Dame and a JD from New York University School of Law.

Mr. Miller joins Phathom as General Counsel from Cyclerion Therapeutics where he served as General Counsel and Secretary. Prior to Cyclerion, he served as Senior Vice President, General Counsel and Secretary of Blue Buffalo where he led all legal activities including those related to the $8 billion acquisition by General Mills. Mr. Miller has also served as Chief Counsel for Pfizer Consumer Healthcare, Chief Counsel for the Pfizer Established Products Business Unit, and General Counsel of Enzon Pharmaceuticals. He holds an AB from Dartmouth College and a JD from Columbia University School of Law.

In addition to the executive appointments, Dr. Parikh joins Phathoms Board of Directors as Chris Slavinsky steps down following his departure from Takeda to join Prometheus Biosciences. Dr. Parikh is currently Senior Vice President and Head of the Gastroenterology Therapeutic Area Unit at Takeda. He brings to Phathoms Board significant gastrointestinal therapeutic area experience, including the global development of Entyvio and Takedas other gastroenterology programs. Dr. Parikh earned his PhD in Biochemistry and MD from Vanderbilt University and completed his internal medicine residency at the University of Pennsylvania. He also completed subspecialty training in gastroenterology at the Massachusetts General Hospital and postdoctoral work in cancer biology at MIT.

I look forward to working with Asit and expect his deep gastroenterology drug development experience will be a tremendous asset to Phathom, said Tadataka (Tachi) Yamada, MD, Chairman of the Board at Phathom. I would also like to extend my sincere thanks to Chris for his instrumental role in shaping Phathom from its inception.

About Phathom

Phathom Pharmaceuticals is a biopharmaceutical company focused on the development and commercialization of novel treatments for gastrointestinal diseases and disorders. Phathom has licensed the exclusive rights in the United States, Europe, and Canada to vonoprazan, a novel potassium competitive acid blocker (P-CAB) in late-stage development for the treatment of acid-related disorders. For more information about Phathom, visit the Companys website at http://www.phathompharma.com.

Forward Looking Statements

The Company cautions you that statements contained in this press release regarding matters that are not historical facts are forward-looking statements. These statements are based on the companys current beliefs and expectations. Such forward-looking statements include, but are not limited to, statements regarding vonoprazan moving into and potential success in the Companys Phase 3 clinical trials and the effect of the Companys planned management transition. The inclusion of forward-looking statements should not be regarded as a representation by the Company that any of its plans will be achieved. Actual results may differ from those set forth in this press release due to the risks and uncertainties inherent in the Companys business, including, without limitation: the Companys ability to recruit patients for Phase 3 clinical trials; the potential for negative clinical trial results; reliance on third parties for manufacturing and certain development efforts; challenges in integrating new members of the management team and board of directors; and the need to continue to attract, integrate, retain and motivate necessary personnel to accomplish the Companys business objectives, as well as other risks described in the companys prior press releases and the Companys filings with the Securities and Exchange Commission (SEC), including under the heading Risk Factors in the Companys Registration Statement on Form S-1 and any subsequent filings with the SEC. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof, and Phathom undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date hereof. All forward-looking statements are qualified in their entirety by this cautionary statement, which is made under the safe harbor provisions of the Private Securities Litigation Reform Act of 1995.

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Phathom Pharmaceuticals Expands Leadership Team and Announces Board Transition - Business Wire

Numero quattro: Immunology experts at deal-focused IFM line up $55.5M for the next leg of their drug exploration journey – Endpoints News

Its pipeline priming time at IFM Therapeutics. And they have the money to get the job done.

The immunology experts at the discovery outfit have lined up $55.5 million in new venture backing from an expanded syndicate still including their big believers at Atlas. And its not hard to figure out the motivation.

Gary Glick, whos moving from CEO to executive chairman on this round, and his team have lined up a slate of deals for their early-stage work.

Just 2 months ago Novartiss NIBR stepped up with an $840 million buyout option tied to research funding for therapeutics that fire up the STING pathway. And theyve reaped more than $600 million in cash from Bristol-Myers and Novartis on both sides of NLRP3, tamping down as well as triggering that pathway, in addition to STING.

The financing will have a goal of graduating 2 programs into subsidiaries, says Martin Seidel, a NIBR vet whos now moving up to the CEO post after running research for IFM over the last couple of years.

Now comes their third subsidiary, IFM Quattro, as the crew also starts their own incubator to play with some new ideas in the field.

Theyre sticking to their area of expertise in the innate immune system, looking for new ways that work in fighting cancer as well as new anti-inflammatories. What exactly is on the horizon is a topic they arent ready to discuss with Endpoints News, but there are a variety of possibilities. Just a couple of weeks ago a group of their scientists and collaborators published new work on the role the inflammasome plays in tau pathology a possible new approach to Alzheimers, where nothing has worked so far.

So the plan at a high level is to continue to execute on the strategy: Take target specific programs into subsidiaries and then hunt up partners around the IND stage, says Lina Gugucheva, the BD chief at IFM. The new venture round will be enough to fuel the company of 35 staffers for the next 3 years or so as it sets up the new subsidiaries and starts to look to execute new deals.

With their track record, backers have good reason to believe that IFM has decent odds of paying off again with a solid multiple in a relatively short span of time. As a result, says Glick, there was plenty of interest from new investors, and they opted to let Omega Funds into the small syndicate, alongside Atlas and Abingworth. Omegas Paulina Hill joins Jean-Francois Formela at Atlas and Shelley Chu from Abingworth on the board.

So whats with the Italian numbering system at IFM? Glick says it was inspired by a traditional 12 course Italian meal. And that leaves IFM preparing the main course.

Social image: Martin Seidel, Gary Glick, Lina Gugucheva

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Numero quattro: Immunology experts at deal-focused IFM line up $55.5M for the next leg of their drug exploration journey - Endpoints News

UC Merced Aims to Draw 1,000 Donors in a Day with ‘Give Tue UC Merced’ Campaign | Newsroom – UC Merced University News

By Michelle Morgante, UC Merced

The annual Give Tue UC Merced campaign takes place on Tuesday, Dec. 3.

Jose Nava-Mejia hopes to work in renewable energy after he graduates from UC Merced. That means every moment spent on his environmental energy courses is a moment invested in the planets future.

Kelsey Duggin hopes to use her microbiology and immunology studies to become a virologist and work with stem cells. Vania Huaranga plans to become a neuropsychologist.

The three are among the scores of UC Merced undergraduates whose studies are backed by the Build the Future Scholarship Fund, which is supported by donations collected during Give Tue UC Merced.

The annual day of giving campaign takes place Tuesday, Dec. 3. During the 24 hours of worldwide Giving Tuesday, UC Merced has set a goal of drawing gifts from 1,000 donors.

Donations designated for the Build the Future Scholarship Fund will be matched 3-to-1 by Foster Poultry Farms, quadrupling the impact of every dollar.

In addition, donors can support UC Merceds Graduate Student Fellowship Fund. The first 100 donations to the fund will be amplified by a matching donation that will provide up to $1,000 from longtime campus friends Dr. Robert Bernstein and Dr. Jane Binger. Vice Provost and Graduate Dean Marjorie Zatz is offering a similar match.

This years Give Tue UC Merced marks the sixth year of the campaign.

Support from the gifts made during Give Tue UC Merced transforms the lives of our students, their families and their communities, interim Chancellor Nathan Brostrom said. Every donation helps us build a better future by supporting the education of the next generation of world-class researchers.

Nava-Mejia, a 19-year-old first-generation student from Merced, said the Build the Future Scholarship allows him to devote more time to his studies.

It means a lot because I can focus on my education, he said. With the scholarship, I can pay for my books and transportation costs. It also lifts a burden off my parents.

UC Merced is a national leader in student outcomes and social mobility, with nine out of 10 students receiving some form of financial assistance. Such financial support was one of the main reasons Duggin decided to enroll.

The support from the Build the Future Scholarship has provided me with the ability to pay for all of the basic necessities, said the second-year student from La Crescenta. It gave me reassurance that hard-working students are rewarded and it motivates me to continue to prioritize my studies.

For Huaranga, a first-year psychology major from Antioch, the Build the Future Scholarship not only provides financial backing, it helps her feel supported as she transitions into college life.

"As a first-generation student, college tuition can be very costly for our families," she said. The Build the Future Scholarship has been very significant to me for many reasons but my main reason is that it gave me a sense that there are people out there who support students. This made me feel that I am not alone and that there are people who believe in me.

"Support from the gifts made during Give Tue UC Merced transforms the lives of our students, their families and their communities.

Last year, the Give Tue UC Merced campaign raised more than $170,000, bringing the total collected over the past five years to more than $1.5 million.

Currently, 144 students are receiving support from the Build the Future Scholarship. And thanks to the generosity of Foster Poultry Farms, there will be a 3-to-1 match on gifts made to the Build the Future Scholarship Fund, up to a total of $100,000 during Give Tue UC Merced.

Online gifts can be directed to givetue.ucmerced.edu ; Donations also will be collected at locations across campus on Tuesday, Dec. 3.

Numerous events will be held on campus throughout the day to raise awareness of Give Tue UC Merced and support a culture of giving back. Housing and Residence Life is organizing a Dollars for Scholars carnival event, including a chance for donors to toss pies at resident assistants and a holiday social featuring an ugly sweater contest. The events are open to all students and a $1 donation is encouraged.

The Graduate Division will offer coffee and churros to donors Tuesday afternoon.

Last year marked the second year in which the campus met its 1,000-donor goal on Give Tue UC Merced. Those donors included nearly 500 students, underscoring a growing tradition of giving among Bobcats.

Huaranga said receiving support from the Build the Future Scholarship has inspired her to want to, in the future, give scholarships that will help students from her hometown attend UC Merced.

Duggin said she also hopes to contribute to the university.

I hope to eventually be able to give back to UC Merced, specifically to benefit the students. I want the future generations to have access to a great education without worrying about finances, Duggin said. Give Tue UC Merced is a great event that allows donors to support the school and the students. Thank you to the donors who invest in the students at UC Merced it really makes a difference.

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UC Merced Aims to Draw 1,000 Donors in a Day with 'Give Tue UC Merced' Campaign | Newsroom - UC Merced University News