Funding, Deals & Partnerships: BIOLOGICS & MEDICAL DEVICES; BioMed e-Series; Medicine and Life Sciences Scientific Journal – http://PharmaceuticalIntelligence.com
Acinetobacter baumannii bacteria that are resistant to important antibiotics called carbapenems. Acinetobacter baumannii are highly-drug resistant bacteria that can cause a range of infections for hospitalized patients, including pneumonia, wound, or blood infections.
Pseudomonas aeruginosa, which are resistant to carbapenems. Pseudomonas aeruginosa can cause skin rashes and ear infectious in healthy people but also severe blood infections and pneumonia when contracted by sick people in the hospital.
Enterobacteriaceae — a family of bacteria that live in the human gut — that are resistant to both carbepenems and another class of antibiotics, cephalosporins.
It has been designated critical need for development of antibiotics to these pathogens. Now researchers at Mcmaster University and others in the US had used artificial intelligence (AI) to screen libraries of over 7,000 chemicals to find a drug that could be repurposed to kill off the pathogen.
Liu et. Al. (1) published their results of an AI screen to narrow down potential chemicals that could work against Acinetobacter baumanii in Nature Chemical Biology recently.
Abstract
Acinetobacter baumannii is a nosocomial Gram-negative pathogen that often displays multidrug resistance. Discovering new antibiotics against A. baumannii has proven challenging through conventional screening approaches. Fortunately, machine learning methods allow for the rapid exploration of chemical space, increasing the probability of discovering new antibacterial molecules. Here we screened ~7,500 molecules for those that inhibited the growth of A. baumannii in vitro. We trained a neural network with this growth inhibition dataset and performed in silico predictions for structurally new molecules with activity against A. baumannii. Through this approach, we discovered abaucin, an antibacterial compound with narrow-spectrum activity against A. baumannii. Further investigations revealed that abaucin perturbs lipoprotein trafficking through a mechanism involving LolE. Moreover, abaucin could control an A. baumannii infection in a mouse wound model. This work highlights the utility of machine learning in antibiotic discovery and describes a promising lead with targeted activity against a challenging Gram-negative pathogen.
Schematic workflow for incorporation of AI for antibiotic drug discovery for A. baumannii from 1. Liu, G., Catacutan, D.B., Rathod, K. et al. Deep learning-guided discovery of an antibiotic targeting Acinetobacter baumannii. Nat Chem Biol (2023). https://doi.org/10.1038/s41589-023-01349-8
Antibiotics kill bacteria. However, there has been a lack of new drugs for decades and bacteria are becoming harder to treat, as they evolve resistance to the ones we have.
More than a million people a year are estimated to die from infections that resist treatment with antibiotics.The researchers focused on one of the most problematic species of bacteria – Acinetobacter baumannii, which can infect wounds and cause pneumonia.
You may not have heard of it, but it is one of the three superbugs the World Health Organization has identified as a “critical” threat.
It is often able to shrug off multiple antibiotics and is a problem in hospitals and care homes, where it can survive on surfaces and medical equipment.
Dr Jonathan Stokes, from McMaster University, describes the bug as “public enemy number one” as it’s “really common” to find cases where it is “resistant to nearly every antibiotic”.
Artificial intelligence
To find a new antibiotic, the researchers first had to train the AI. They took thousands of drugs where the precise chemical structure was known, and manually tested them on Acinetobacter baumannii to see which could slow it down or kill it.
This information was fed into the AI so it could learn the chemical features of drugs that could attack the problematic bacterium.
The AI was then unleashed on a list of 6,680 compounds whose effectiveness was unknown. The results – published in Nature Chemical Biology – showed it took the AI an hour and a half to produce a shortlist.
The researchers tested 240 in the laboratory, and found nine potential antibiotics. One of them was the incredibly potent antibiotic abaucin.
Laboratory experiments showed it could treat infected wounds in mice and was able to kill A. baumannii samples from patients.
However, Dr Stokes told me: “This is when the work starts.”
The next step is to perfect the drug in the laboratory and then perform clinical trials. He expects the first AI antibiotics could take until 2030 until they are available to be prescribed.
Curiously, this experimental antibiotic had no effect on other species of bacteria, and works only on A. baumannii.
Many antibiotics kill bacteria indiscriminately. The researchers believe the precision of abaucin will make it harder for drug-resistance to emerge, and could lead to fewer side-effects.
In principle, the AI could screen tens of millions of potential compounds – something that would be impractical to do manually.
“AI enhances the rate, and in a perfect world decreases the cost, with which we can discover these new classes of antibiotic that we desperately need,” Dr Stokes told me.
The researchers tested the principles of AI-aided antibiotic discovery in E. coli in 2020, but have now used that knowledge to focus on the big nasties. They plan to look at Staphylococcus aureus and Pseudomonas aeruginosa next.
“This finding further supports the premise that AI can significantly accelerate and expand our search for novel antibiotics,” said Prof James Collins, from the Massachusetts Institute of Technology.
He added: “I’m excited that this work shows that we can use AI to help combat problematic pathogens such as A. baumannii.”
Prof Dame Sally Davies, the former chief medical officer for England and government envoy on anti-microbial resistance, told Radio 4’s The World Tonight: “We’re onto a winner.”
She said the idea of using AI was “a big game-changer, I’m thrilled to see the work he (Dr Stokes) is doing, it will save lives”.
Other related articles and books published in this Online Scientific Journal include the following:
Series D: e-Books on BioMedicine – Metabolomics, Immunology, Infectious Diseases, Reproductive Genomic Endocrinology
“A miracle that came true”. This is how Aviva Lev-Ari, PhD, RN founder of LPBI Group’s described what she and her venture had accomplished by partnering with Montero for a “monumental” #Medicine and #LifeSciences translation project. It was “monumental” because it involved 18 books in medicine 😊.
Dr. Lev-Ari is the editor-in-chief behind the Medicine and Life Sciences Scientific Journal, PharmaceuticalIntelligence.com An open access scientific journal that has over 2.2 million views by over 1.4 million visitors. Over 6,170 scientific articles and over 740 categories of research in its ontology.
Between June 2013 and February 2021, LPBI Group’s team published eighteen 𝗲𝗹𝗲𝗰𝘁𝗿𝗼𝗻𝗶𝗰 medical 𝗯𝗼𝗼𝗸𝘀 covering five medical specialties:
These e-books, including 𝟮,𝟳𝟮𝟴 scientific 𝗮𝗿𝘁𝗶𝗰𝗹𝗲𝘀 curated and authored 𝗯𝘆 𝗯𝗶𝗼𝗺𝗲𝗱𝗶𝗰𝗮𝗹 experts and medical 𝗽𝗿𝗼𝗳𝗲𝘀𝘀𝗶𝗼𝗻𝗮𝗹𝘀 pursuing the quest to make the latest research available to healthcare professionals and accessible to the Global community of biological scientists, practicing physicians and medical students.
With 471,000 million speakers in 22 countries, the Spanish language was the most relevant language to publish a new edition.
So, it was time to find the right #LanguageServiceProvider. Dr. Lev-Ari first contacted:
1️⃣ A company that couldn’t handle the project due to its size.
2️⃣ Another provider whose quote they couldn’t accept.
This led LPBI to adjust the scope of work and set certain boundaries, such as the budget for the project and making the decision that the project will focus on translation of the cover page of 18 e-books and the electronic Table of Contents (eTOCs) of these e-Books.
And then Aviva came across Fritz Handtke and Montero on LinkedIn. We held a couple of meetings to:
🤝 Define the scope of the project.
🤝 Create a methodology we could repeat 18 times.
🤝 Show LPBI how we work, including the software used to avoid counting (and charging for) repeated words.
🤝 Introduce our experts in the medical field to them.
Aviva’s acceptance of our quote marked the beginning of a very smooth collaboration.
It took us less than five months, involving three #MedicalTranslators, to deliver the eTOCs in Spanish (for 𝟭𝟵 𝗯𝗼𝗼𝗸𝘀 divided into five series).
The result of this project was “a new genre of the original #biomed e-Series.” In each volume of the Spanish-language Edition: PART A is Spanish audios, PART B is Bilingual texts, and PART C is editorials in English.
When we asked Dr. Lev-Ari about her experience with Montero, she highlighted the following points:
1️⃣ “At all times, there was 𝗼𝗻𝗲 𝘀𝗶𝗻𝗴𝗹𝗲 𝗽𝗲𝗿𝘀𝗼𝗻 𝗮𝘀𝘀𝗶𝗴𝗻𝗲𝗱 𝘁𝗼 𝗺𝘆 𝗽𝗿𝗼𝗷𝗲𝗰𝘁.”
2️⃣ “One of the editors of the series A in cardiovascular is a Spanish-speaking cardiologist. He reviewed 2 books and confirmed the 𝘁𝗿𝗮𝗻𝘀𝗹𝗮𝘁𝗶𝗼𝗻 𝗮𝗰𝗰𝘂𝗿𝗮𝗰𝘆.”
3️⃣ “Their 𝗿𝗲𝘀𝗽𝗼𝗻𝘀𝗲 𝘁𝗶𝗺𝗲 was most favorable. After submitting a file, I got the translation within a week. For any questions, I’d receive a timely response.”
Imagine how thrilled we were to hear her say:
“Congratulations to Montero because they delivered a very monumental project. Without our collaboration, that would have most likely not have happened.”
Thanks to Aviva and LPBI Group for your trust in Montero!
percutaneous Left Ventricular Assist Device (pLVAD) – An Israeli startup, Magenta Medical, behind the world’s smallest heart pump has raised $55 million
Curator: Aviva Lev-Ari, PhD, RN
May 3, 2023 at 8am EST
Magenta Medical Closes $55M Funding Round Led by OrbiMed
Funding will further Magenta’s clinical programs in support of FDA approval for world’s smallest heart pump
Kadima, Israel – May 03, 2023 –Magenta Medical, developer of the world’s smallest heart pump, announced today a $55M financing round led by global healthcare investment manager OrbiMed, with participation from existing investors New Enterprise Associates (NEA), Pitango VC, and ALIVE – Israel HealthTech Fund. The financing will be used, among other things, to advance the clinical programs of the company’s product in the United States towards its first FDA approval.
Temporary mechanical circulatory support (MCS) is one of the fastest growing markets in interventional cardiology, encompassing devices that aim to augment the output of a failing heart, in the setting of dangerously low blood pressure, while resting the heart and providing a bridge to recovery over a period of hours or days. Existing temporary MCS devices provide limited flow, require an invasive surgical procedure, or both.
Magenta’s percutaneous Left Ventricular Assist Device (pLVAD) is a powerful heart pump that is initially folded, inserted through the groin using a small puncture, and expanded for activation inside the left ventricle. The flow of the pump is adjusted based on the clinical circumstances of the patient, up to the entire cardiac output, allowing the heart to rest and the patient to recover. Once the Magenta technology is approved, physicians will be able to rely on a single device to treat the full range of MCS patients, thus eliminating the need to escalate therapy to a new device and subject the patient to unnecessary and invasive replacement procedures.
“Magenta is proud to add OrbiMed to its growing roster of leading MedTech investors as a highly reputable partner for innovative medical device companies,” said Dr. David Israeli, CEO of Magenta Medical. “I am confident that together we can build an organization well-equipped to bring to the market high-impact technology that can potentially address multiple unmet needs in the general cardiology patient population, as well as in many under-served patient groups.”
The potential advantages of Magenta’s high-flow, low-profile device were recognized by the US FDA, resulting in Breakthrough Device Designation for two indications: high-risk percutaneous coronary intervention (HR-PCI) and cardiogenic shock (CS).
Magenta successfully completed a HR-PCI first-in-human (FIH) study in Tbilisi, Georgia, the results of which were presented at the recent 2022 Transcatheter Cardiovascular Therapeutics (TCT) conference in Boston, MA, by Dr. Duane Pinto of Beth Israel Deaconess Medical Center and Harvard Medical School. Building on this experience, Magenta is now preparing to launch its clinical programs in the US, starting with an imminent HR-PCI Early Feasibility Study.
“Having supported Magenta’s FIH study, I was thoroughly impressed with the unique combination of a low-profile device delivering best-in-class flow,” said Dr. Pinto. “Magenta’s device is inserted with ease percutaneously and can accommodate the full gamut of flows required by MCS patients in the various situations I encounter as an interventional cardiologist. Use of this technology can be mastered by a wide range of proceduralists to better address the unmet needs of contemporary patients, such as those with small or challenging vascular anatomies, especially if high flows are needed.”
“We are excited to have identified the merits of Magenta’s technology, with its strong disruptive potential, and are extremely pleased with the relationships that we have built with management, the founders, and the existing investors,” said Dr. David Bonita, General Partner at OrbiMed. “We look forward to advancing the clinical programs and accelerating the introduction of this important technology to the market in the US and globally.”
Magenta’s proprietary technology miniaturizes a powerful percutaneous Left Ventricular Assist Device to fit an 8 Fr delivery system – the smallest crimping profile of any such device. The pump is inserted percutaneously, over a guidewire, through the aorta and across the aortic valve, using commercially available 10 Fr introducer sheaths. Employing standard catheterization techniques and equipment for placement has important advantages in terms of ease-of-use, safety, physician access, and vascular access closure. Once deployed inside the heart, the speed of the pump can be adjusted to provide more than 5 L/min of mean blood flow at physiological blood pressures – the full cardiac output of an adult – allowing the heart to rest and the patient to recover. With peak flows exceeding 7 L/min, this is the most powerful known percutaneous pump, comparing favorably even with surgically placed catheter pumps that have more than twice Magenta’s insertion profile.
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About Magenta Medical
Magenta Medical Ltd. is a privately-held company dedicated to the development of miniaturized blood pumps intended to provide minimally-invasive support to the native heart during acute episodes of dysfunction that could lead to dangerously low blood pressure and compromised perfusion of vital organs. Magenta’s Elevate™ percutaneous left ventricular assist device is currently in clinical testing, with the ultimate goal of securing approval for at least two indications: patients undergoing high-risk coronary interventions and patients with cardiogenic shock. Magenta Medical was founded by two serial entrepreneurs, Professor Ehud Schwammenthal and Mr. Yosi Tuval, who previously founded Ventor Technologies – a medical device company that was acquired by Medtronic in 2009. For more info, visit https://magentamed.com/.
About OrbiMed
OrbiMed is a healthcare investment firm, with approximately $17 billion in assets under management. OrbiMed invests globally across the healthcare industry through a range of private equity funds, public equity funds, and royalty/credit funds. OrbiMed’s team of over 100 professionals is based in New York City, San Francisco, Shanghai, Hong Kong, Mumbai, Herzliya and other key global markets.
Magenta has developed a miniaturized catheter-mounted axial flow-pump for mechanical circulatory support of the left ventricle.
Israeli company Magenta Medical has announced the completion of a $55 million financing round led by OrbiMed Advisors and with the participation of previous investors NEA, Pitango and Alive.Magenta has developed a miniaturized catheter-mounted axial flow-pump for mechanical circulatory support of the left ventricle, based on Magenta’s core technology of a self-expanding impeller and pump head. The self-expanding impeller is comprised of a thin memory-shape metallic frame and a soft, flexible material that forms the body of the blades.
Magenta Medical was founded in 2012 by CMO Prof. Ehud Schwammenthal and CTO Dr. Yosi Tuva, who had previously founded heart valve developer Ventor, which was sold to Medtronic in 2009 for $350 million. Magenta’s CEO is Dr. David Israeli, a former senior executive at Medtronic and Pitango, which invested in the company. Magenta has raised $100 million to date.
Dr. Israel told “Globes” that Magenta has changed its focus in recent years but not its technology – only the use it is aiming for. The pump was first developed to treat heart failure and was intended to be implanted in the renal veins to regulate blood pressure and evacuate salts and fluids – an improved replacement for diuretic drugs that are the standard treatment for heart failure, but they are not always helpful, and may have side effects. This product was already advanced, so with the company’s previous fundraising, it believed it could get the product approved without additional fundraising.
The reason for the change was the realization that the road to approval was longer than it seemed at first, because there is no such product on the market, and it was necessary to develop the protocol from start to finish, together with the FDA, and then overcome another hurdle of proving the economic value of the product to obtain insurance indemnity. So even though the product worked well, and despite (or rather because) there being no similar solutions on the market, the road looked too long and uncertain.
Meanwhile, another area began to capture the company’s attention: using a coronary artery pump to support patients arriving at the hospital with acute heart failure or undergoing high-risk interventional catheterization. The pump supports the heart’s activity and can even replace it until it recovers.
The field called Temporary Mechanical Circulatory Support has been growing in recent years led by Johnson & Johnson unit Abiomed. Magenta believes that as other products have already trod the regulatory path and then received insurance indemnity, the way forward in this sector is clearer while there remains plenty of room in the market for their distinct product.
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NEA makes first Israeli investment in Magenta Medical
The product has undergone trials with 15 patients in Georgia and is now undergoing a trial with 15 more patients in the US.
Published by Globes, Israel business news – en.globes.co.il – on May 3, 2023.
An Israeli startup behind the world’s smallest heart pump has raised $55 million.
Magenta Medical’s device will be used to support patients arriving at the hospital with heart failure, or undergoing high-risk treatments to alleviate their symptoms.
The pump can support the heart’s activity, and even replace it for several days until it recovers, by temporarily opening clogged arteries in the hearts of cardiac patients, and improving symptoms like chest pain and shortness of breath.
The pump is folded up and inserted through a catheter via the groin. Once it has been guided to the heart’s left ventricle (which is responsible for pumping oxygenated blood all over the body), and the catheter has been removed, it expands by up to three and a half times.
Inside the heart, the speed of the pump can be adjusted to provide more than five liters of blood a minute – the full cardiac output of an adult at rest. The company says the pump is more powerful than others, with peak flows exceeding seven liters per minute.
Existing temporary devices provide a more limited flow of oxygenated blood to the body’s tissues or require an invasive surgical procedure – or both.
Magenta Medical’s product has undergone trials with 15 patients in Georgia, USA. The company is now preparing to launch its clinical programs in the US. The financing will be used to advance the clinical programs of the product towards its first FDA approval.
The funding was raised by global healthcare investment manager OrbiMed, with participation from existing investors New Enterprise Associates, Pitango VC, and ALIVE – Israel HealthTech Fund.
“Magenta is proud to add OrbiMed to its growing roster of leading MedTech investors as a highly reputable partner for innovative medical device companies,” said CEO Dr. David Israeli.
“I am confident that together we can build an organization well-equipped to bring to the market high-impact technology that can potentially address multiple unmet needs in the general cardiology patient population, as well as in many under-served patient groups.”
Magenta Medical was founded in 2012, and is based in Kadima Zoran, central Israel.
In Cardiology, “Interventional” is reserved for procedures that directly produce physical changes. Surgical interventions for cardiovascular diseases include heart or heart and lung transplant, implantation of cardiac assist devices, shock devices and pacemakers, bypass grafts for coronary or other arteries, valve repairs or replacement, removal of plaque (endarterectomy), removal of tumors, and repair or palliation of injuries or of congenital anomalies. All of these interventions are continually studied and improved, with a major effort at minimizing the risk, reducing recovery time and reducing the size of entry scar, for example by use of video scopes instead of direct visualization, and mechanical devices and robotics instead of direct manual access. Interventional Cardiology refers to an often competing non-surgical approach in which access is limited to entry by vein or artery (catheterization). The two teams have joined forces to achieve a major success in replacing aortic valves by femoral artery access without opening the chest at all (TAVR), with on-going progress towards a similar approach to mitral valve replacement.
This book addresses disease prevalence, personalized patient and doctor experiences with Cardiac Surgery, the role of transfusion, status of the MedTech market, and a review of major accomplishments from pathology, anesthesiology, radiology, cardiology and surgery. The contributions of specific groups, such as the Texas Heart Institute, the Dalio Institute at New York Presbyterian/Weill Cornell, the Cleveland Clinic, and the Scripps Institute are reviewed. Individual contributions from Eric Topol, Arthur Moss, Paul Zoll, Tim Wu, and Earl E. Bakken (Medtronic co-founder) are included. Discoveries in relevant biology, including ATP (the metabolic paycheck) and plasma metabolomics, and novel technologies such as tethered-liquid perfluorocabon surface biocoating to prevent clotting. Additional curations present views of cardiothoracic surgeons, vascular surgeons and of Catheterization lab interventionists. Business aspects are addressed by review of costs, prevalence, payment methods, prevention impact and business models. Decision support tools are also reviewed, and changes in guidelines. Voices of three Open Heart Surgery Survivors are included. Chapters 4-6 addressed clinical trial data in coronary disease, biomarkers of cardiovascular disorders, coagulation including top roles of nitric oxide, C-reative protein, protein C, aprotinin and thrombin. Chapters 7-8 covered amyloidosis, atherosclerosis, valve disease, flow reserve, atrial fibrillation and roles for advanced imaging. Chapters 9-10 covered unstable angina, transplants, and ventricular assist devices. Chapters 11-14 span interventions on the aorta, peripheral arteries, and coronary arteries, valve surgery and percutaneous valve repair or replacement, plus the growing role of prosthetics and repair by stem cells and tissue engineering.
As catheter techniques evolved to compete with bypass surgery they progressed from balloon cracking of obstructive lesions (POBA=plain old balloon angioplasty) to placement of stents (wire fences). Surgeons sometimes use in-stent valves, and now devices analogous to in-stent valves can be placed by catheter for valve replacement in patients with too much co-morbidity to go through heart surgery. Aortic valve replacement by stent (TAVR) has had sufficient success to be considered for all patients who have sufficient impairment to merit intervention. The diameter is large, so a vascular surgeon participates in the arterial access and repair of the access site.
Minimally invasive repair of abdominal aorta aneurysm: atherosclerosis offers potentially somewhat protective stiffening of the arterial wall, it can promote clots, athero-emboli, and failure of the remodeling can lead to an outward ballooning, or aneurysm, that promotes both clot formation and wall or lining tears or rupture, cause of sudden death.
Chapter 7: Ventricular Failure: Assist Devices, Surgical and Non-Surgical
7.1 Trends in the Industry
The Voice of Series A Content Consultant: Justin D. Pearlman, MD, PhD, FACC
In addition to minimally invasive treatments for coronary disease and valve disease, there are minimally invasive alternatives to heart transplant for the dangerously weak heart (extreme heart failure) which can otherwise result in Cardiogenic Shock. These involve various means to augment or complement the pumping function of the heart, such as a Ventricular Assist Device (VAD) .
With respect to the performance of Mitral Valve Replacement, the current practice favors bioprosthetic valves over mechanical valve replacement for most patients, initially just used for elderly to avoid need for coumadin, but now used at younger ages due to improvements in longevity of the bioprosthetic valves, plus less damage to red cells.
7.1.1 Spectranetics, a Technology Leader in Medical Devices for Coronary Intervention, Peripheral Intervention, Lead Management to be acquired by Philips for 1.9 Billion Euros
7.2.4 Experimental Therapy (Left inter-atrial shunt implant device) for Heart Failure: Expert Opinion on a Preliminary Study on Heart Failure with preserved Ejection Fraction
7.3.1 Dilated Cardiomyopathy: Decisions on implantable cardioverter-defibrillators (ICDs) using left ventricular ejection fraction (LVEF) and Midwall Fibrosis: Decisions on Replacement using late gadolinium enhancement cardiovascular MR (LGE-CMR)
Amyloidosis inserts abnormal proteins into tissues – in the heart, that results in an insidious decline cardiac function marked by increased stiffness (requiring high filling pressures that wet the lungs) and decreased contractility or inotropy (pumping ability). resulting in poor circulation of nutrients to tissues and organs. Amyoloidosis is suspected when imaging shows thickened heart muscle and thickened valves with reduced function, but thickened muscle also occurs as a reaction to incomplete control of elevated blood pressures, as well as by other infiltrative disorders.
microRNA (miRNA) miR-483-5p has a key role in preventing stress-related anxiety by acting on its target gene Pgap2 that curbs the development of this type of anxiety
Severe psychological trauma triggers genetic, biochemical and morphological changes in amygdala neurons, which underpin the development of stress-induced behavioural abnormalities, such as high levels of anxiety. miRNAs are small, non-coding RNA fragments that orchestrate complex neuronal responses by simultaneous transcriptional/translational repression of multiple target genes. Here we show that miR-483-5p in the amygdala of male mice counterbalances the structural, functional and behavioural consequences of stress to promote a reduction in anxiety-like behaviour. Upon stress, miR-483-5p is upregulated in the synaptic compartment of amygdala neurons and directly represses three stress-associated genes: Pgap2, Gpx3 and Macf1. Upregulation of miR-483-5p leads to selective contraction of distal parts of the dendritic arbour and conversion of immature filopodia into mature, mushroom-like dendritic spines. Consistent with its role in reducing the stress response, upregulation of miR-483-5p in the basolateral amygdala produces a reduction in anxiety-like behaviour. Stress-induced neuromorphological and behavioural effects of miR-483-5p can be recapitulated by shRNA mediated suppression of Pgap2 and prevented by simultaneous overexpression of miR-483-5p-resistant Pgap2. Our results demonstrate that miR-483-5p is sufficient to confer a reduction in anxiety-like behaviour and point to miR-483-5p-mediated repression of Pgap2 as a critical cellular event offsetting the functional and behavioural consequences of psychological stress.
The female reproductive lifespan is regulated by the menstrual cycle. Defined as the interval between the menarche and menopause, it is approximately 35 years in length on average. Based on current average human life expectancy figures, and excluding fertility issues, this means that the female body can bear children for almost half of its lifetime. Thus, within this time span many individuals may consider contraception at some point in their reproductive life. A wide variety of contraceptive methods are now available, which are broadly classified into hormonal and non-hormonal approaches. A normal menstrual cycle is controlled by a delicate interplay of hormones, including estrogen, progesterone, follicle-stimulating hormone (FSH) and luteinizing hormone (LH), among others. These molecules are produced by the various glands in the body that make up the endocrine system.
Hormonal contraceptives – including the contraceptive pill, some intrauterine devices (IUDs) and hormonal implants – utilize exogenous (or synthetic) hormones to block or suppress ovulation, the phase of the menstrual cycle where an egg is released into the uterus. Beyond their use as methods to prevent pregnancy, hormonal contraceptives are also being increasingly used to suppress ovulation as a method for treating premenstrual syndromes. Hormonal contraceptives composed of exogenous estrogen and/or progesterone are commonly administered artificial means of birth control. Despite many benefits, adverse side effects associated with high doses such as thrombosis and myocardial infarction, cause hesitation to usage.
Scientists at the University of the Philippines and Roskilde University are exploring methods to optimize the dosage of exogenous hormones in such contraceptives. Their overall aim is the creation of patient-specific minimizing dosing schemes, to prevent adverse side effects that can be associated with hormonal contraceptive use and empower individuals in their contraceptive journey. Their research data showed evidence that the doses of exogenous hormones in certain contraceptive methods could be reduced, while still ensuring ovulation is suppressed. Reducing the total exogenous hormone dose by 92% in estrogen-only contraceptives, or the total dose by 43% in progesterone-only contraceptives, prevented ovulation according to the model. In contraceptives combining estrogen and progesterone, the doses could be reduced further.
Named for ACGT co-founder, Edward Netter, the award recognizes a researcher who has made unparalleled and groundbreaking contributions to the field of cell and gene therapy for cancer. Dr. Mackall is a leader in advancing cell and gene therapies for the treatment of solid tumors, with a major focus on children’s cancers.
In addition to being an ACGT research fellow and a member of ACGT’s Scientific Advisory Council, Dr. Mackall is the Ernest and Amelia Gallo Family professor of Pediatrics and Medicine at Stanford University, the founding director of the Stanford Center for Cancer Cell Therapy, associate director of the Stanford Cancer Institute, leader of the Cancer Immunotherapy Program and director of the Parker Institute for Cancer Immunotherapy. She has led numerous groundbreaking clinical trials to treat children with sarcomas and brain cancers.
“There is exciting progress happening in the field of cancer cell and gene therapy,” said Kevin Honeycutt, CEO and president of ACGT. “We continue to see the FDA approve cell and gene therapy treatments for blood cancers, while research for solid tumors is now progressing to clinical trials. These successes are linked to the funding of ACGT, and Dr. Crystal Mackall is one of the best examples of a researcher who refused to accept the status-quo of standard cancer treatment and committed to developing novel cell and gene therapies for children with difficult-to-treat tumors. ACGT is proud that Dr. Mackall is an ACGT Research Fellow, a member of ACGT’s Scientific Advisory Council, and the newest recipient of the Edward Netter Leadership Award.”
The ACGT Awards Luncheon will celebrate the non-profit organization’s 20th anniversary and usher in a new decade as the only nonprofit dedicated exclusively to funding cancer cell and gene therapy research. ACGT funds innovative scientists and biotechnology companies working to harness the power of cell and gene therapy to transform how cancer is treated and to drive momentum toward a cure.
The Edward Netter Leadership Award will be presented to Dr. Mackall by Carl June, MD, of the University of Pennsylvania, who received the honor at ACGT’s 2019 Awards Gala. ACGT grant funding enabled Dr. June to research and develop cell and gene therapies that led to the first FDA approvals of CAR T-cell therapies for cancer.
For more than 20 years, Alliance for Cancer Gene Therapy has funded research that is bringing innovative treatment options to people living with deadly cancers – treatments that save lives and offer new hope to all cancer patients. Alliance for Cancer Gene Therapy funds researchers who are pioneering the potential of cancer cell and gene therapy – talented visionaries whose scientific advancements are driving the development of groundbreaking treatments for ovarian, prostate, sarcoma, glioblastoma, melanoma and pancreatic cancers. One hundred percent of all public funds raised by Alliance for Cancer Gene Therapy directly support research and programs. For more information, visit acgtfoundation.org, call (203) 358-5055, or join the Alliance for Cancer Gene Therapy community on Facebook, Twitter, LinkedIn, Instagram and YouTube @acgtfoundation.
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Other Related Articles in this Open Access Scientific Journal Include
How to Create a Twitter Space for @pharma_BI for Live Broadcasts
Right now, Twitter Spaces are available on Android and iOS operating systems ONLY. For use on a PC desktop you must install an ANDROID EMULATOR. This means best to set up the Twitter Space using your PHONE APP not on the desktop or laptop computer. Right now, even though there is the ability to record a Twitter Space, that recording is not easily able to be embedded in WordPress as a tweet is (or chain of tweets). However you can download the recording (takes a day or two) and convert to mpeg using a program like Audacity to convert into an audio format conducible to WordPress.
A while ago I had put a post where I link to a Twitter Space I created for a class on Dissemination of Scientific Discoveries. The post
This online discussion was tweeted out and got a fair amount of impressions (60) as well as interactors (50).
About Twitter Spaces
Spaces is a way to have live audio conversations on Twitter. Anyone can join, listen, and speak in a Space on Twitter for iOS and Android. Currently you can listen in a Space on web.
The creator of a Space is the host. As a host on iOS, you can start a Space by long pressing on the Tweet Composer from your Home timeline and and then selecting the Spaces icon.
You can also start a Space by selecting the Spaces tab on the bottom of your timeline.
Step 2
Spaces are public, so anyone can join as a listener, including people who don’t follow you. Listeners can be directly invited into a Space by DMing them a link to the Space, Tweeting out a link, or sharing a link elsewhere.
Step 3
Up to 13 people (including the host and 2 co-hosts) can speak in a Space at any given time. When creating a new Space, you will see options to Name your Space and Start your Space.
Step 4
To schedule a Space, select Schedule for later. Choose the date and time you’d like your Space to go live.
Step 5
Once the Space has started, the host can send requests to listeners to become co-hosts or speakers by selecting the people icon and adding co-hosts or speakers, or selecting a person’s profile picture within a Space and adding them as a co-host or speaker. Listeners can request permission to speak from the host by selecting the Request icon below the microphone.
Step 6
When creating a Space, the host will join with their mic off and be the only speaker in the Space. When ready, select Start your Space.
Step 7
Allow mic access (speaking ability) to speakers by toggling Allow mic access to on.
Step 8
Get started chatting in your Space.
Step 9
As a host, make sure to Tweet out the link to your Space so other people can join. Select the icon to Share via a Tweet.
Spaces FAQ
Where is Spaces available?
Anyone can join, listen, and speak in a Space on Twitter for iOS and Android. Currently, starting a Space on web is not possible, but anyone can join and listen in a Space.
Who can start a Space?
People on Twitter for iOS and Android can start a Space.
Who can see my Space?
For now, all Spaces are public like Tweets, which means they can be accessed by anyone. They will automatically appear at the top of your Home timeline, and each Space has a link that can be shared publicly. Since Spaces are publicly accessible by anyone, it may be possible for people to listen to a Space without being listed as a guest in the Space.
We make certain information about Spaces available through the Twitter Developer Platform, such as the title of a Space, the hosts and speakers, and whether it is scheduled, in progress, or complete. For a more detailed list of the information about Spaces we make available via the Twitter API, check out our Spaces endpoints documentation.
Can other people see my presence while I am listening or speaking in a Space?
Since all Spaces are public, your presence and activity in a Space is also public. If you are logged into your Twitter account when you are in a Space, you will be visible to everyone in the Space as well as to others, including people who follow you, people who peek into the Space without entering, and developers accessing information about the Space using the Twitter API.
If you are listening in a Space, your profile icon will appear with a purple pill at the top of your followers’ Home timelines. You have the option to change this in your settings.
Instructions for:
Manage who can see your Spaces listening activity
Step 1
On the left nav menu, select the more icon and go to Settings and privacy.
Step 2
Under Settings, navigate to Privacy and safety.
Step 3
Under Your Twitter activity, go to Spaces.
Step 4
Choose if you want to Allow followers to see which Spaces you’re listening to by toggling this on or off.
Your followers will always see at the top of their Home timelines what Spaces you’re speaking in.
What does it mean that Spaces are public? Can anyone listen in a Space?
Spaces can be listened to by anyone on the Internet. This is part of a broader feature of Spaces that lets anyone listen to Spaces regardless of whether or not they are logged in to a Twitter account (or even have a Twitter account). Because of this, listener counts may not match the actual number of listeners, nor will the profile photos of all listeners necessarily be displayed in a Space.
How do I invite people to join a Space?
Invite people to join a Space by sending an invite via DM, Tweeting the link out to your Home timeline, or copying the invite link to send it out.
Who can join my Space?
For now, all Spaces are public and anyone can join any Space as a listener. If the listener has a user account, you can block their account. If you create a Space or are a speaker in a Space, your followers will see it at the top of their timeline.
Who can speak in my Space?
By default, your Space will always be set to Only people you invite to speak. You can also modify the Speaker permissions once your Space has been created. Select the icon, then select Adjust settings to see the options for speaker permissions, which include Everyone, People you follow, and the default Only people you invite to speak. These permissions are only saved for this particular Space, so any Space you create in the future will use the default setting.
Once your Space has started, you can send requests to listeners to become speakers or co-hosts by selecting the icon and adding speakers or selecting a person’s profile picture within a Space and adding them as a co-host or speaker. Listeners can request to speak from the host.
Hosts can also invite other people outside of the Space to speak via DM.
How does co-hosting work?
Up to 2 people can become co-hosts and speak in a Space in addition to the 11 speakers (including the primary host) at one time. Co-host status can be lost if the co-host leaves the Space. A co-host can remove their own co-host status to become a Listener again.
Hosts can transfer primary admin rights to another co-host. If the original host drops from Space, the first co-host added will become the primary admin. The admin is responsible for promoting and facilitating a healthy conversation in the Space in line with the Twitter Rules.
Once a co-host is added to a Space, any accounts they’ve blocked on Twitter who are in the Space will be removed from the Space.
Can I schedule a Space?
Hosts can schedule a Space up to 30 days in advance and up to 10 scheduled Spaces. Hosts can still create impromptu Spaces in the meantime, and those won’t count toward the maximum 10 scheduled Spaces.
Before you create your Space, select the scheduler icon and pick the date and time you’d like to schedule your Space to go live. As your scheduled start time approaches, you will receive push and in-app notifications reminding you to start your Space on time. If you don’t have notifications turned on, follow the in-app steps on About notifications on mobile devices to enable them for Spaces. Scheduled Spaces are public and people can set reminders to be notified when your scheduled Space begins.
How do I edit my scheduled Space(s)?
Follow the steps below to edit any of your scheduled Spaces.
Instructions for:
Manage your scheduled Spaces
Step 1
From your timeline, navigate to and long press on the . Or, navigate to the Spaces Tab at the bottom of your timeline.
Step 2
Select the Spaces icon.
Step 3
To manage your scheduled Spaces, select the scheduler icon at the top.
Step 4
You’ll see the Spaces that you have scheduled.
Step 5
Navigate to the more icon of the Space you want to manage. You can edit, share, or cancel the Space.
If you are editing your Space, make sure to select “Save changes” after making edits.
How do I get notified about a scheduled Space?
Guests can sign up for reminder notifications from a scheduled Space card in a Tweet. When the host starts the scheduled Space, the interested guests get notified via push and in-app notifications.
Can I record a Space?
Hosts can record Spaces they create for replay. When creating a Space, toggle on Record Space.
While recording, a recording symbol will appear at the top to indicate that the Space is being recorded by the host. Once the Space ends, you will see how many people attended the Space along with a link to share out via a Tweet. Under Notifications, you can also View details to Tweet the recording. Under host settings, you will have the option to choose where to start your recording with Edit start time. This allows you to cut out any dead air time that might occur at the beginning of a Space.
If you choose to record your Space, once the live Space ends, your recording will be immediately and publicly available for anyone to listen to whenever they want. You can always end a recording to make it no longer publicly available on Twitter by deleting your recording via the more icon on the recording itself. Unless you delete your recording, it will remain available for replay after the live Space has ended.* As with live Spaces, Twitter will retain audio copies for 30 after they end to review for violations of the Twitter Rules. If a violation is found, Twitter may retain audio copies for up to 120 days in total. For more information on downloading Spaces, please see below FAQ, “What happens after a Space ends and is the data retained anywhere?”
Co-hosts and speakers who enter a Space that is being recorded will see a recording symbol (REC). Listeners will also see the recording symbol, but they will not be visible in the recording.
Recordings will show the host, co-host(s), and speakers from the live Space.
*Note: Hosts on iOS 9.15+ and Android 9.46+ will be able to record Spaces that last indefinitely. For hosts on older app versions, recording will only be available for 30 days. For Spaces that are recorded indefinitely, Twitter will retain a copy for as long as the Space is replayable on Twitter, but for no less than 30 days after the live Space ended.
What is clipping?
Clipping is a new feature we’re currently testing and gradually rolling out that lets a limited group of hosts, speakers, and listeners capture 30 seconds of audio from any live or recorded Space and share it through a Tweet if the host has not disabled the clipping function. To start clipping a Space, follow the instructions below to capture the prior 30 seconds of audio from that Space. There is no limit to the number of clips that participants in a Space can create.
When you enter the Space as a co-host or speaker, you will be informed that the Space is clippable through a tool tip notification above the clipping icon.
Note: Currently, creating a clip is available only on iOS and Android, while playing a clip is available on all platforms to everyone.
Instructions for:
Host instructions: How to turn off clipping
When you start your Space, you’ll receive a notification about what a clip is and how to turn it off, as clipping is on by default. You can turn off clipping at any time. To turn it off, follow the instructions below.
Step 1
Navigate to the more icon.
Step 2
Select Adjust settings .
Step 3
Under Clips, toggle Allow clips off.
Instructions for:
Host and speaker instructions: How to create a clipping
Step 1
In a recorded or live Space that is recorded, navigate to the clipping icon. Please note that, for live Spaces, unless the clipping function is disabled, clips will be publicly available on your Twitter profile after your live Space has ended even though the Space itself will no longer be available.
Step 2
On the Create clip pop-up, go to Next.
Step 3
Preview the Tweet and add a comment if you’d like, similarly to a Quote Tweet.
Step 4
Select Tweet to post it to your timeline.
Why is my clip not displaying captions?
What controls do hosts have over existing clips?
What controls do clip creators have over clips they’ve created?
Other controls over clips: how to report, block, or mute
What controls do I have over my Space?
The host and co-host(s) of a Space have control over who can speak. They can mute any Speaker, but it is up to the individual to unmute themselves if they receive speaking privileges. Hosts and co-hosts can also remove, report, and block others in the Space.
Speakers and listeners can report and block others in the Space, or can report the Space. If you block a participant in the Space, you will also block that person’s account on Twitter. If the person you blocked joins as a listener, they will appear in the participant list with a Blocked label under their account name. If the person you blocked joins as a speaker, they will also appear in the participant list with a Blocked label under their account name and you will see an in-app notification stating, “An account you blocked has joined as a speaker.” If you are entering a Space that already has a blocked account as a speaker, you will also see a warning before joining the Space stating, “You have blocked 1 person who is speaking.”
If you are hosting or co-hosting a Space, people you’ve blocked can’t join and, if you’re added as a co-host during a Space, anyone in the Space who you blocked will be removed from the Space.
What are my responsibilities as a Host or Co-Host of a Space?
As a Host, you are responsible for promoting and supporting a healthy conversation in your Space and to use your tools to ensure that the Twitter Rules are followed. The following tools are available for you to use if a participant in the Space is being offensive or disruptive:
Revoke speaking privileges of other users if they are being offensive or disruptive to you or others
Block, remove or report the user.
Here are some guidelines to follow as a Host or Co-Host:
Always follow the Twitter Rulesin the Space you host or co-host. This also applies to the title of your Space which should not include abusive slurs, threats, or any other rule-violating content.
Do not encourage behavior or content that violates the Twitter Rules.
Do not abuse or misuse your hosting tools, such as arbitrarily revoking speaking privileges or removing users, or use Spaces to carry out activities that break our rules such as following schemes.
How can I block someone in a Space?
How can I mute a speaker in a Space?
How can I see people in my Space?
Hosts, speakers, and listeners can select the icon to see people in a Space. Since Spaces are publicly accessible by anyone, it may also be possible for an unknown number of logged-out people to listen to a Space’s audio without being listed as a guest in the Space.
How can I report a Space?
How can I report a person in a Space?
Can Twitter suspend my Space while it’s live?
How many people can speak in a Space?
How many people can listen in a Space?
What happens after a Space ends and is the data retained anywhere?
Hosts can choose to record a Space prior to starting it. Hosts may download copies of their recorded Spaces for as long as we have them by using the Your Twitter Data download tool.
For unrecorded Spaces, Twitter retains copies of audio from recorded Spaces for 30 days after a Space ends to review for violations of the Twitter Rules. If a Space is found to contain a violation, we extend the time we maintain a copy for an additional 90 days (a total of 120 days after a Space ends) to allow people to appeal if they believe there was a mistake. Twitter also uses Spaces content and data for analytics and research to improve the service.
Links to Spaces that are shared out (e.g., via Tweet or DM) also contain some information about the Space, including the description, the identity of the hosts and others in the Space, as well as the Space’s current state (e.g., scheduled, live, or ended). We make this and other information about Spaces available through the Twitter Developer Platform. For a detailed list of the information about Spaces we make available, check out our Spaces endpoints documentation.
For full details on what data we retain, visit our Privacy Policy.
Who can end a Space?
Does Spaces work for accounts with protected Tweets?
Following the Twitter Rules in Spaces
Spaces Feedback Community
We’re opening up the conversation and turning it over to the people who are participating in Spaces. This Community is a dedicated place for us to connect with you on all things Spaces, whether it’s feedback around features, ideas for improvement, or any general thoughts.
Who can join?
Anyone on Spaces can join, whether you are a host, speaker, or listener.
How do I join the Community?
You can request to join the Twitter Spaces Feedback Community here. By requesting to join, you are agreeing to our Community rules.
As a Community admin or moderator, you can create and host a Space for your Community members to join.
Note:
Currently, creating Community Spaces is only available to some admins and moderators using the Twitter for iOS and Twitter for Android apps.
Instructions for:
Admins & moderators: How to create a Space
Step 1
Navigate to the Community landing page.
Step 2
Long press on the Tweet Composer and select the Spaces icon.
Step 3
Select Spaces and begin creating your Space by adding in a title, toggling on record Space (optional), and adding relevant topics.
Step 4
Invite admins, moderators, and other people to be a part of your Space.
Members: How to find a Community Space
If a Community Space is live, you will see the Spacebar populate at the top of your Home timeline. To enter the Space and begin listening, select the live Space in the Spacebar.
Community Spaces FAQ
What are Community Spaces?
Spaces Social Narrative
A social narrative is a simple story that describes social situations and social behaviors for accessibility.
Twitter Spaces allows me to join or host live audio-only conversations with anyone.
Joining a Space
When I join a Twitter Space, that means I’ll be a listener. I can join any Space on Twitter, even those hosted by people I don’t know or follow.
I can join a Space by selecting a profile photo with a purple, pulsing outline at the top of my timeline, selecting a link from someone’s Tweet, or a link in a Direct Message (DM).
Once I’m in a Space, I can seethe profile photos and names of some people in the Space, including myself.
I can hearone or multiple people talking at the same time. If it’s too loud or overwhelming, I can turn down my volume.
As a listener, I am not able to speak. If I want to say something, I can send a request to the host. The host might not approve my request though.
If the host accepts my request, I will become a speaker. It may take a few seconds to connect my microphone, so I’ll have to wait.
Now I can unmute myself and speak. Everyone in the Space will be able to hear me.
When someone says something I want to react to, I can choosean emoji to show everyone how I feel. I will be able to see when other people react as well.
I can leave the Space at any time. After I leave, or when the host ends the Space, I’ll go back to my timeline.
Hosting a Space
When I start a Space, that means I’ll be the host. Anyone can join my Space, even people I don’t know and people I don’t follow.
Once I start my space, it may take a few seconds to be connected, so I’ll have to wait.
Now I’m in my Space and I can seemy profile photo. If other logged-in, people have joined, I will be able to see their profile photos, too.
I will start out muted, which is what the microphone with a slash through it means. I can mute and unmute myself, and anyone in my Space, at any time.
I can invitepeople to join my Space by sending them a Direct Message (DM), sharing the link in a Tweet, and by copying the link and sharing it somewhere else like in an email.
Up to 10 other people can have speaking privileges in my Space at the same time, and I can choosewho speaks and who doesn’t. People can also request to speak, and I can choose to approve their request or not.
The Vibrant Philly Biotech Scene: Recent Happenings & Deals
Curator: Stephen J. Williams, Ph.D.
As the office and retail commercial real estate market has been drying up since the COVID pandemic, commercial real estate developers in the Philadelphia area have been turning to the health science industry to suit their lab space needs. This includes refurbishing old office space as well as new construction.
Gattuso secures $290M construction loan for life sciences building on Drexel campus
By Ryan Mulligan – Reporter, Philadelphia Business Journal
Dec 19, 2022
Gattuso Development Partners and Vigilant Holdings of New York have secured a $290 million construction loan for a major life sciences building set to be developed on Drexel University’s campus.
The funding comes from Houston-based Corebridge Financial, with an additional equity commitment from Boston-based Baupost Group, which is also a partner on the project. JLL’s Capital Markets group arranged the loan.
Plans for the University City project at 3201 Cuthbert St. carry a price tag of $400 million. The 11-story building will total some 520,000 square feet, making it the largest life sciences research and lab space in the city when it comes online.
The building at 3201 Cuthbert will rise on what had served as a recreation field used by Drexel and is located next to the Armory. Gattuso Development, which will lease the parcel from Drexel, expects to to complete the project by fall 2024. Robert A.M. Stern Architects designed the building.
A rendering of a $400 million lab and research facility Drexel University and Gattuso Development Partners plan to build at 3201 Cuthbert St. in Philadelphia.
The building is 45% leased by Drexel and SmartLabs, an operator of life sciences labs. Drexel plans to occupy about 60,000 square feet, while SmartLabs will lease two floors totaling 117,000 square feet.
“We believe the project validates Philadelphia’s emergence as a global hub for life sciences research, and we are excited to begin construction,” said John Gattuso, the co-founder and president of Philadelphia-based Gattuso Development.
Ryan Ade, Brett Segal and Christopher Peck of JLL arranged the financing.
Tmunity CEO Usman Azam departing to lead ‘stealth’ NYC biotech firm
By John George – Senior Reporter, Philadelphia Business Journal
Feb 7, 2022
The CEO of one of Philadelphia’s oldest cell therapy companies is departing to take a new job in the New York City area.
Usman “Oz” Azam, who has been CEO of Tmunity Therapeutics since 2016, will lead an unnamed biotechnology company currently operating in stealth mode.
In a posting on his LinkedIn page, Azam said, “After a decade immersed in cell therapies and immuno-oncology, I am now turning my attention to a new opportunity, and will be going back to where I started my life sciences career in neurosciences.”
Tmunity, a University of Pennsylvania spinout, is looking to apply CAR T-cell therapy, which has proved to be successful in treating liquid cancers, for the treatment of solid tumors.
Last summer, Tmunity suspended clinical testing of its lead cell therapy candidate targeting prostate cancer after two patients in the study died. Azam, in an interview with the Business Journal in June, said the company, which had grown to about 50 employees since its launch in 2015, laid off an undisclosed number of employees as a result of the setback.
Azam said on LinkedIn he is still a big believer in CAR T-cell therapy, noting Tmunity co-founder Dr. Carl June and his colleagues at Penn just published in Nature the 10-year landmark clinical outcomes study with the first CD19 CAR-T patients and programs.
“It’s just the beginning,” he stated. “I’m excited about the prospect of so many new cell- and gene-based therapies emerging in the next five to 10 years to tackle many solid and liquid tumors, and I hope we all continue to see the remarkable impact this makes on patients and families around the world.”
Azam could not be reached for comment Monday. Tmunity has engaged a search firm to identify his successor.
Tmunity, which is based in Philadelphia, has its own manufacturing operations in East Norriton. Tmunity’s founders include June and fellow Penn cell therapy pioneer Bruce Levine, who led the development of a CAR T-cell therapy now marketed by Novartis as Kymriah, a treatment for certain types of blood cancers.
In therapy using CAR-T cells, a patient’s T cells — part of their immune system — are removed and genetically modified in the laboratory. After they are re-injected into a patient, the T cells are better able to attack and destroy tumors. CAR is an acronym for chimeric antigen receptor. Chimeric antigen receptors are receptor proteins that have been engineered to give T cells their improved ability to target tumors.
Jodie Harris is a Philadelphia native who has spent the last 15 years in the U.S. Department of Treasury.
By Ryan Mulligan – Reporter, Philadelphia Business Journal
The Philadelphia Industrial Development Corp. has tapped U.S. Department of Treasury veteran Jodie Harris to be its next president.
Harris succeeds Anne Bovaird Nevins, who spent 15 years in the organization and took over as president in January 2020 before stepping down at the end of last year. Executive Vice President Sam Rhoads has been interim president.
Harris, a Philadelphia native who currently serves as director of the Community Development Financial Institutions Fund for the Department of Treasury, was picked after a regional and national search and will begin her tenure as president on June 1. She becomes the 12th head of PIDC and the first African-American woman to lead the organization.
PIDC is a public-private economic development corporation founded by the city and the Chamber of Commerce for Greater Philadelphia in 1958. It mainly uses industrial and commercial real estate projects to attract jobs, foster business opportunities and spur overall community growth. The organization has spurred over $18.5 billion in financing across its 65 years.
In a statement, Harris said that it is “a critical time for Philadelphia’s economy.”
“I’m especially excited for the opportunity to lead such an important and impactful organization in my hometown of Philadelphia,” Harris said. “As head of the CDFI Fund, I know first-hand what it takes to drive meaningful, sustainable, and equitable economic growth, especially in historically underserved communities.”
Harris is a graduate of the University of Maryland and received an MBA and master of public administration from New York University. In the Treasury Department, Harris’ most recent work aligns with PIDC’s economic development mission. At the Community Development Financial Institutions Fund, she oversaw a $331 million budget, mainly comprised of grant and administrative funding for various economic programs. Under Harris’ watch, the fund distributed over $3 billion in pandemic recovery funding, its highest level of appropriated grants ever.
Harris has been a part of the Treasury Department for 15 years, including as director of community and economic development policy.
In addition to government work, Harris has previously spent time in the private, academia and nonprofit sectors. In the beginning of her career, Harris worked at Meridian Bank and Accenture before turning to become a social and education policy researcher at New York University. She also spent two years as president of the Urban Business Assistance Corporation in New York.
Mayor Jim Kenney said that Philadelphia is “poised for long-term growth” and Harris will help drive it.
Real estate company SkyREM plans to spend $250 million converting the historic Quartermaster site in South Philadelphia to a life sciences campus with restaurants and a hotel.
The redevelopment would feature wet and dry lab space for research, development and bio-manufacturing.
The renamed Quartermaster Science + Technology Park is near the southwest corner of Oregon Avenue and South 20th Street in the city’s Girard Estates neighborhood. It’s east of the Quartermaster Plaza retail center, which sold last year for $100 million.
The 24-acre campus is planned to have six acres of green space, an Aldi grocery store opening by March and already is the headquarters for Indego, the bicycle share program in Philadelphia.
Six buildings totaling 1 million square feet of space would be used for research and development labs. There’s 500,000 square feet of vacant space available for life sciences and high technology companies with availabilities as small as 1,000 square feet up to 250,000 square feet contiguous. There’s also 150,000 square feet of retail space available.
The office park has 200,000 square feet already occupied by tenants. The Philadelphia Job Corps Center and Delaware Valley Intelligence Center are tenants at the site.
A rendering shows part of the Quartermaster Science + Technology Park as a redeveloped mixed-use life science campus.
QUARTERMASTER / PROVIDED BY FIFTEEN
The campus was previously used by the military as a place to produce clothing, footwear and personal equipment during World War I and II. The clothing factory closed in 1994. The Philadelphia Quartermaster Depot was listed on the National Register of Historic Places in 2010.
“We had a vision to preserve the legacy of this built-to-last historic Philadelphia landmark and transform it to create a vibrant space where the best and brightest want to innovate, collaborate, and work,” SkyREM CEO and Founder Alex Dembitzer said in a statement.
SkyREM, a real estate investor and developer, has corporate offices in New York and Philadelphia. The company acquired the site in 2001.
Vered Nohi, SkyREM’s regional executive director of new business development, called the redevelopment “transformational” for Philadelphia.
SkyREM announced the redevelopment of the Quartermaster campus in South Philadelphia into a life sciences campus with restaurants and a hotel. This rendering looks across Oregon Avenue toward the southwest corner of Oregon and 21st Street.
QUARTERMASTER / PROVIDED BY FIFTEEN
Quartermaster would join a wave of new life sciences projects being developed in the surrounding area and across the region.
The site is near both interstates 76 and 95 and is about 2 miles north of the Philadelphia Navy Yard, which has undergone a similar transformation from a military hub to a major life sciences and mixed-use redevelopment project. The Philadelphia Industrial Development Corp. is also in the process of selecting a developer to create a massive cell and gene therapy manufacturing complex across two sites totaling about 40 acres on Southwest Philadelphia’s Lower Schuylkill riverfront.
A rendering shows part of the future Quartermaster Science and Technology Park in South Philadelphia. The 24-acre campus is planned to have six buildings with 1 million square feet of life science space.
QUARTERMASTER / PROVIDED BY FIFTEEN
SkyREM is working with Maryland real estate firm Scheer Partners to lease the science and technology space. Philadelphia’s MPN Realty will handle leasing of the retail space. Architecture firm Fifteen is working on the project’s design.
Scheer Partners Senior Vice President Tim Conrey said the Quartermaster conversion will help companies solve for “speed to market” as demand for life science space in the region has been strong.
Brandywine Realty Trust originally planned to redevelop a Radnor medical office into lab and office space, split 50-50 between the two uses.
After changes in demand for lab and office space, Brandywine (NYSE: BDN) recently completed the 168,000-square-foot, four-story building at 250 King of Prussia Road in Radnor fully for life sciences.
“The pipeline is now 100% life sciences, which, while requiring more capital, is also generating longer term leases at a higher return on cost,” Brandywine CEO Jerry Sweeney of the project said during the company’s fourth-quarter earnings call on Thursday.
At the same time, Brandywine is holding off on developing new office buildings unless it has a tenant lined up in advance.
The shift reflects how Philadelphia-based Brandywine continues to lean into — and bet big — on life sciences.
Brandywine is the city’s largest owner of trophy office buildings and has several major development projects in the works. The company is planning to eventually develop 3 million square feet of life sciences space. For now, 800,000 square feet of life sciences space is under development, including a 12-story, 417,000-square-foot life sciences building at 3151 Market St. and a 29-story building with 200,000 square feet of life sciences space at 3025 John F. Kennedy Blvd. Both are part of the multi-phase Schuylkill Yards project underway near 30th Street Station in University City.
Once its existing projects are completed, Brandywine would have 800,000 square feet of life sciences space, making up 8% of its portfolio.Sweeney said the company wants to grow that figure to 21%.
Brandywine is developing a 145,000-square-foot, build-to-suit office building at 155 King of Prussia Road in Radnor for Arkema, a France-based global supplier of specialty materials. The building will be Arkema’s North American headquarters. Construction began in January and is scheduled to be completed in late 2024.
Brandywine reported that since November it raised over $705 million through fourth-quarter asset sales, an unsecured bond transaction and a secured loan. The company has “complete availability” on its $600 million unsecured line of credit, Sweeney said.
Brandywine sold a 95% leased, 86,000-square-foot office building at 200 Barr Harbor Drive in West Conshohocken for $30.5 million. The company also sold its 50% ownership interest in the 1919 Market joint venture for $83.2 million to an undisclosed buyer. 1919 Market St. is a 29-story building with apartments, office and commercial space. Brandywine co-developed the property with LCOR and the California State Teacher’s Retirement System.
Brandywine declined to comment and LCOR could not be reached.
Brandywine’s core portfolio is 91% leased.
The project at 250 King of Prussia Road cost $103.7 million and was recently completed. The renovation included 12-foot high floor-to-ceiling glass on the second floor, a new roof, lobby, elevator core, common area with a skylight and an added structured parking deck.
Located in the Radnor Life Science Center, a new campus with nearly 1 million square feet of lab, research and office space, Sweeney said it’s a “magnet” for biotech companies. Avantor, a global manufacturer and distributor of life sciences products, is headquartered in the complex.
Sweeney said Brandywine is “very confident” demand will stay strong for life sciences in Radnor. The building at 250 King of Prussia Road is projected to be fully leased by early 2024.
“Larger users we’re talking to, they just tend to take a little bit more time than we would like as they go through technical requirements and space planning requirements,” Sweeney said.
While Brandywine is aiming to increase its life sciences footprint, the company is being selective about what it builds next. The company may steer away from developments other than life sciences. The Schuylkill Yards project, for example, features a significant life sciences portion in University City.
“Other than fully leased build-to-suit opportunities, our future development starts are on hold,” Sweeney said, “pending more leasing on the existing joint venture pipeline and more clarity on the cost of debt capital and cap rates.”
Brandywine said about 70% to 75%of suburban tenants have returned to offices while that number has been around 50% in Philadelphia. At this point, though, it hasn’t yet affected demand when leasing space. Some tenants, for example, have moved out of the city while others have moved in.
In the fourth quarter, Brandywine had $55.7 million funds from operations, or 32 cents per share. That’s down from $60.4 million, or 35 cents per share, in the fourth quarter of 2021. Brandywine generated $129 million in revenue in the fourth quarter, up slightly from $125.5 in the year-ago period.
Brandywine stock is up 6.4% since the start of the year to $6.70 per share on Monday afternoon.
Many of Brandywine’s properties are in desirable locations, which have seen demand remain strong despite challenges facing offices, on par with industry trends.
Brandywine’s 12-story, 417,000-square-foot building at 3151 Market St. is on budget for $308 million and on schedule to be completed in the second quarter of 2024. Sweeney said Brandywine anticipates entering a construction loan in the second half of 2023, which would help complete the project. The building, being developed along with a global institutional investor,would be used for life sciences, innovation and office space as part of the larger Schuylkill Yards development in University City.
The company’s 29-story building at 3025 John F. Kennedy Blvd. with 200,000 square feet of life sciences space and 326 luxury apartments, is also on budget, costing $287.3 million, and on time, eyeing completion in the third quarter of this year.
Peak oxygen uptake (VO2peak) quantified fitness: Lifelong and late-onset athletes had higher VO2peak than non-athletes
Reporter: Aviva Lev-Ari, PhD, RN
Lifelong endurance sport participation is not associated with a more favorable coronary plaque composition compared to a healthy lifestyle. Lifelong endurance athletes had more coronary plaques, including more non-calcified plaques in proximal segments, than fit and healthy individuals with a similarly low cardiovascular risk profile. Longitudinal research is needed to reconcile these findings with the risk of cardiovascular events at the higher end of the endurance exercise spectrum.
The median age was 55 (50–60) years in all groups
191 lifelong master endurance athletes,
191 late-onset athletes (endurance sports initiation after 30 years of age), and
176 healthy non-athletes,
all male with a low cardiovascular risk profile, were included.
Lifelong and late-onset athletes had higher VO2peak than non-athletes
159 [143-177] vs
155 [138-169] vs
122 [108-138] % predicted).
Lifelong endurance sports was associated with having
≥1 coronary plaque (odds ratio [OR] 1.86, 95% confidence interval [CI] 1.17–2.94), ≥1 proximal plaque (OR 1.96, 95% CI 1.24–3.11),
≥1 calcified plaques (OR 1.58, 95% CI 1.01–2.49),
≥1 calcified proximal plaque (OR 2.07, 95% CI 1.28–3.35),
≥1 non-calcified plaque (OR 1.95, 95% CI 1.12–3.40),
≥1 non-calcified proximal plaque (OR 2.80, 95% CI 1.39–5.65) and
≥1 mixed plaque (OR 1.78, 95% CI 1.06–2.99) as compared to a healthy non-athletic lifestyle.
SOURCE
Lifelong endurance exercise and its relation with coronary atherosclerosis
Ruben De Bosscher, MD, Christophe Dausin, MSc, Piet Claus, MSc PhD, Jan Bogaert, MD PhD, Steven Dymarkowski, MD PhD, Kaatje Goetschalckx, MD, Olivier Ghekiere, MD PhD, Caroline M Van De Heyning, MD PhD, Paul Van Herck, MD PhD, Bernard Paelinck, MD PhD, Haroun El Addouli, MD PhD, André La Gerche, MD PhD, Lieven Herbots, MD PhD, Rik Willems, MD PhD, Hein Heidbuchel, MD FESC FEHRA PhD, Guido Claessen, MD PhD, Master@Heart Consortium, Lifelong endurance exercise and its relation with coronary atherosclerosis, European Heart Journal, 2023;, ehad152, https://doi.org/10.1093/eurheartj/ehad152
06 March 2023
Abstract
Background and Aims
The impact of long-term endurance sport participation (on top of a healthy lifestyle) on coronary atherosclerosis and acute cardiac events remains controversial.
Methods
The Master@Heart study is a well-balanced prospective observational cohort study. Overall, 191 lifelong master endurance athletes, 191 late-onset athletes (endurance sports initiation after 30 years of age), and 176 healthy non-athletes, all male with a low cardiovascular risk profile, were included. Peak oxygen uptake (VO2peak) quantified fitness. The primary endpoint was the prevalence of coronary plaques (calcified, mixed, and non-calcified) on computed tomography coronary angiography. Analyses were corrected for multiple cardiovascular risk factors.
Results
The median age was 55 (50–60) years in all groups. Lifelong and late-onset athletes had higher VO2peak than non-athletes (159 [143-177] vs 155 [138-169] vs 122 [108-138] % predicted). Lifelong endurance sports was associated with having ≥1 coronary plaque (odds ratio [OR] 1.86, 95% confidence interval [CI] 1.17–2.94), ≥1 proximal plaque (OR 1.96, 95% CI 1.24–3.11), ≥1 calcified plaques (OR 1.58, 95% CI 1.01–2.49), ≥1 calcified proximal plaque (OR 2.07, 95% CI 1.28–3.35), ≥1 non-calcified plaque (OR 1.95, 95% CI 1.12–3.40), ≥1 non-calcified proximal plaque (OR 2.80, 95% CI 1.39–5.65) and ≥1 mixed plaque (OR 1.78, 95% CI 1.06–2.99) as compared to a healthy non-athletic lifestyle.
Conclusion
Lifelong endurance sport participation is not associated with a more favorable coronary plaque composition compared to a healthy lifestyle. Lifelong endurance athletes had more coronary plaques, including more non-calcified plaques in proximal segments, than fit and healthy individuals with a similarly low cardiovascular risk profile. Longitudinal research is needed to reconcile these findings with the risk of cardiovascular events at the higher end of the endurance exercise spectrum.
Other related articles on coronary atherosclerosis published in this Open Access Online Scientific Journal include the following:
176 articles under Atherogenic Processes & Pathology Category
Atherosclerosis Independence: Genetic Polymorphisms of Ion Channels Role in the Pathogenesis of Coronary Microvascular Dysfunction and Myocardial Ischemia (Coronary Artery Disease (CAD))
Reviewer and Co-Curator: Larry H Bernstein, MD, FCAP
Entering the last day of the American College of Cardiology’s annual conference, the Big Pharma is trotting out new phase 2 data of its anti-PCSK9 drug, finding that it reduced particular kinds of cholesterol by up to 61% compared to placebo.
Meanwhile, expanded phase 3 data of sotatercept, added onto background therapy, has exceeded the expectations of Chief Medical Officer Eliav Barr, M.D. “It just hits the right receptor,” he said in an interview with Fierce Biotech.
Sotatercept was the prized jewel in the company’s $11.5 billion purchase of Acceleron Pharma in 2021. The cardio med aimed at treating pulmonary arterial hypertension improved patients’ six-minute walk distance by more than 40 meters after 24 weeks compared to placebo, hitting the primary endpoint of the 323-patient trial.
The therapy also reduced the risk of clinical worsening or death by 84% compared to placebo for a median follow-up of 32.7 weeks, according to the conference presentation.What’s more, sotatercept had a slightly lower discontinuation rate due to treatment-related side effects than placebo patients.
While sotatercept has accrued much of the acclaim for the cardio team, Barr was also riding the high of positive phase 2 data from the company’s oral PCSK9 inhibitor to treat high cholesterol. The trial compared four doses of MK-0616 in patients with high cholesterol compared to placebo; all four were found to significantly reduce LDL cholesterol levels.
The highest dose of the med reduced levels of this cholesterol by more than 60% compared to placebo and the number of side effects across all dose levels was consistent with placebo.
The data is naturally a critical checkpoint as Barr and Merck tout the value of the first oral version of the therapy class currently dominated by Amgen’s Repatha and Regeneron’s Praluent. Next on the clinical docket is a phase 3 trial slated for the second half of the year, but Barr also hopes to launch a cardiovascular outcomes trial before year-end as well.
Cholesterol Lowering Novel PCSK9 drugs: Praluent [Sanofi and Regeneron] vs Repatha [Amgen] – which drug cuts CV risks enough to make it cost-effective?
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