Monthly Archives: July 2020

Physiology

The psychology and physiology of pain management in athletics – AW – Athletics Weekly

Gateshead International Athletics Stadium, July 31, 1983

With just one week to go before the inaugural World Championships in Helsinki, some of the sports top names are fine-tuning their preparations before jetting off to Finland.

As a bridging distance between 800m and 1500m, the mens 1000m has attracted an international field of half milers and milers. As they take the bell in a respectable 1:26.58, a familiar face on the European circuit is leading in his distinctive white vest and matching wristbands.

Down the back straight for the last time and BBC Grandstand commentator David Coleman is waxing lyrical about the virtues of the elegant striding American out in front. This being said, the man who will go on to record a lifetime best of 1:44.62 over two laps in Stockholm a year later is most certainly a specialist half miler and the rolling of his head as the 800m point fast approaches, signals an impending changing of the guard.

At that moment, Moscow Olympic 800m champion Steve Ovett predictably devastatingly kicks and opens up a gap on the field with Don Paige giving dogged, if eventually futile, chase over the final 200 metres. An unflustered Ovett stops the clock at 2:19.06, saving his customary wave to the crowd until after the finishing line on this occasion.

Further down the field, the battle for the minor places continues as 1976 Olympic 1500m champion John Walker edges past the long-time race leader, whose shoulders have by now joined his head in rotational motion and who will eventually finish in fifth place.

Thirty-seven years later, laughing as he recalls his capitulation over the final furlong, James Mays jokes: I was left looking like the coyote in an episode of Wile E. Coyote and the Road Runner! His lay citation to matters of the zoological continue as comparisons to a North American species of canine are soon superseded by reference to a mammal namely monkeys.

The man who achieved international recognition for his pacemaking work in the 1980s, which famously included guiding Steve Cram to a world mile record in Oslo in the summer of 1985, recalls: When I was running at Texas Tech, my team-mates coined the phrase Monkey City. I thought it was funny and a great description of how a runner feels when theyre in the final push of a race.

The thought of monkeys riding your back with the sound of eek, eek in your ear was quite amusing!

In his moment of jest, the three-time All American collegiate champion may well be speaking words of truth and offering us a few hidden gems in terms of both the psychology and physiology of pain management among athletes.

The sensation of pain occurs as a result of brain neuronal activity in the encephalon. The experience of pain is of course unpleasant but a necessity when one considers its vitality as a signalling function which enables us to ultimately avoid death and maintain homeostasis in biological terms.

The functionality of pain is that it serves as an adaptive function, allowing us as athletes to know when we have encountered our optimal load, be it in the realms of running, jumping or throwing. In disaggregating the notion of pain, Domzal (1996) spoke about three facets in terms of the somatic (sensual feeling), the cognitive (psychological) and emotional (which is the value judgement we place on pain). This is compatible with the work of Azevedo and Samulski (2003), who noted that while athletes seem to have pain thresholds similar to non-athletes, critically their tolerance to pain may well be higher. So in essence, its not what we experience biologically, but how we perceive that experience psychologically.

Pain is subjective and relative which is why the man who now teaches both at school and university level in his native Dallas continues: Of course there are times when you dont feel like youre attacked by monkeys, but actual gorillas!

What Mays might be referring to would be classified by the likes of Haythornwaite et al (1998) as a specific form of coping strategy for pain management. Rather than ignoring Monkey City, Mays recollections of that Gateshead race challenge us as to whether we should adopt a strategy of Mindfulness based upon acceptance that as endurance-based athletes, at some point in our races we will inevitably feel as if we live in such a frightening urban metropolis. This again has some support from the sports psychology literature in that Salwin and Zajac (2016) perceptively point out: Knowing when to expect the difficulties makes it easier for the competitor to prepare and overcome them This means that an athlete can, to a certain degree, prepare for pain.

So rather than running away from pain, we should actually be prepared to hug and embrace it.

While psychologically it clearly helped an athlete like Mays to objectify and externalise his pain as a monkey, references to Monkey City were shared among his collegiate athlete community. This means they must be understood at the sociological level because shared humour is subcultural and its learned behaviour.

This is no surprise in that pain is central to our sport. The ability to joke about pain is functional for us athletes and there is of course a plethora of literature around how humour can keep us well both psychologically and biologically (See Hassed, 2001). Humour is a necessity, not during a race but certainly when embarking upon the slog of training its a defence mechanism against quitting.

While psychologically accepting that one will encounter pain, elite level performers like Mays will always attempt to develop physiological strategies to try and deal with the build-up of acid in their blood which is one of the biological drivers of the psychological experience of inhabiting Monkey City.

In recent years, the esteemed Oregon-based coach Peter Thompson (see http://www.newintervaltraining.com) has done much good work to further the understanding of what exercise physiologists would term acidosis. When lactic acid is formed it dissociates into lactate and acid, the latter of which is formed of hydrogen ions. At the point at which the production of hydrogen ion exceeds the bodys ability to buffer and clear because the kidneys and lungs cant keep the systems pH in balance, acidosis is said to occur and thus athletes enter the gateways of Monkey City.

At the appropriate point of the periodisation cycle, intense training simply has to be performed in order to both physically and psychologically prepare both body and mind to cope with the accumulation of high amounts of hydrogen ions, which may be perceived as Monkey City in experiential terms.

In previous decades, coach education discourses have incorrectly termed this as lactate tolerance training. The aforementioned Thompson perceptively points out that a more useful term is in fact acidosis tolerance training because lactate itself can be functional for the body.

So how did Mays prepare in terms of the specificity of his own acidosis tolerance training for his visit to Monkey City?

The workout that I did which best prepared me to negotiate Monkey City was a 600m speed endurance, he says. I would run to the 600m mark and then jog 150m through the curve, turn around and jog back to the 200m start. At that point I would blast the final 200m.

I would do three sets of those and at the end I was totally exhausted but it simulated in the 800m and I felt it prepared me to compete at a higher level.

The work of the late national coach for middle-distance, Dave Sunderland (2005), would frame this as an event specific session. The three golden rules of this mode of session are (1) that each set always adds up to the target race distance; (2) that work is grouped into sets in order to allow sufficient recovery to undertaken work which challenges the lactate energy system; and (3) that second and/or third set repetition lengths tend to be shorter the than first set.

So it should be noted that Mays practice of this type of session included a differential element in terms of pacing namely that the 200m effort would be effected at a greater average pace than that over 600m. Additionally, unlike the doctrine offered by Sunderland (2005), he has undertaken sets of the same length of repetitions. So while Mays has deviated from a textbook way of undertaking event specific repetitions, he has done so in a way which serves his own individual developmental needs while remaining faithful to the underlying ethos or spirit of this mode of session.

So while Mays was a world-class 800m runner, lets take Sunderlands example of a world-class 1500m runner aiming to hypothetically run 3:30 first set = 500m (70s); 1 min recovery; 700m (98s); 30 sec recovery; 300m (42s) 15-20 min recovery. Second set = 5x300m (42s) 1 min recovery between repetitions.

The strengths of using the kind of event specific repetitions utilised by the man who was a regular for Team USA in the 1980s, along with the likes of Johnny Gray and Earl Jones, are that they are invaluable preparation for ones visit to Monkey City. The cautionary note is that this mode of session tends to be effected in the competition phase of the periodisation cycle only. This mode of session cannot be performed consistency over several months due to the considerable demands on the lactate energy system and excessive use will risk the kind of fatigue which can lead to both subsequent loss of form and potential injury.

The moral of the story is if you want to deal with the monkey on your back it is well worth having a natter to the man affectionately known as The Rabbit!

Questions for self-reflection

Matt Long is a former winner of the British Milers Club Horwill Award for Coach Education and the author of more than 250 coaching articles.He can be contacted at [emailprotected] for advice on this piece

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The psychology and physiology of pain management in athletics - AW - Athletics Weekly

Physiology

U of A ranked among world’s top energy research universities – Folio – University of Alberta

The University of Alberta is among the worlds best, if not the best, energy research universities according to an updated version of the QS World University Rankings by Subject, which also placed the U of A in the top 10 of sport-related subjects for the fourth year in a row.

The amended 2020 version of the subject rankings saw the U of A land in the top 50 in three new energy-related categoriespetroleum engineering (eighth), geophysics (46th) and geology (50th)to go with a previous 11th-place ranking in mining and minerals.

Clayton Deutsch, director of the U of As School of Mining and Petroleum Engineering, said part of the programs success is the impact alumni are having on the mining industry.

You go around to different mining schools around the world, there will be U of A alumni there, said Deutsch. In mining companies all over the world, there are always U of A alumni around there.

He also said the programs approach of being committed academically while remaining practical is what places the U of As mining education among the worlds best.

Even despite some economic woes in the province, we have essentially 100 per cent employment of our students graduating within six months of finishing, said Deutsch. We do that by remaining current and steadfast in our focus on solving real-world mining problems.

One of the enduring legacies of Kerry Mummery, outgoing dean of the Faculty of Kinesiology, Sport, and Recreation, will be the university ranked in the top 10 in the category of sport-related fields in each of the final four years of his tenure, up to seventh from ninth this year.

"During my tenure as dean, I've had the pleasure of working with and bringing in some of the top professors in their field," said Mummery. "I've always been impressed with the quality of their work and how that work makes its way into the classroom to provide our students with a solid foundation of knowledge they wouldn't have found anywhere else."

In the original rankings published in March, other U of A subjects that made the top 50 included nursing, which fought its way back into the top 20 to land at 18th; earth and marine sciences, which rose from 44th to tie for 41st; education, which rebounded from 47th to stick at 44th; and anatomy and physiology, which ranked 44th.

James Young, professor and chair of the U of As Department of Physiology, said he pins the U of As excellence in physiology to strategic recruitment pushes over the past four decades.

We've had sustained recruitment of really excellent young faculty members who want to be part of an excellent environment, and we offer that, said Young. They're not just joining the Department of Physiology, they're joining the faculty and becoming part of a number of research institutes and facilities that really are world class.

Overall, the U of A ranked in the top 100 in 17 subjects and 38 in the top 250. No ranked subject had the U of A lower than ninth nationally, and the university was ranked top five in Canada in 21 categories.

As for the five broad subject ranks, the U of A moved up seven spots to 90th in life sciences and medicine, while dipping slightly in engineering and technology (down to 112 from 107), natural sciences (111 to 116) and arts and humanities (137 to 143). Social sciences and management surged 12 spots to finish at 160.

The methodology for compiling each subject ranking can vary greatly and depends on the publishing rates in each area. Academic reputation, which accounts for anywhere from 30 to 90 per cent of the weight given in determining the rank in a subject area, draws on responses from thousands of academics worldwide.

Other measures include employer reputation, which makes up between 10 and 30 per cent of the measure; citations per paper, which also accounts for between 10 and 30 per cent; and h-indexa way of measuring both the productivity and impact of an academic's published workwhich is valued anywhere from 10 to 30 per cent.

The success in this latest QS ranking follows news in October that the U of A moved back into the top five in Maclean's 2020 Canadian University Rankings, thanks in part to strong showings by the faculties of nursing, business and science.

In August, the ShanghaiRanking Consultancys 2019 Academic Ranking of World Universities by Subject saw the U of A jump into an eighth-place tie with Princeton in the category of environmental science and engineering. Overall, the U of A finished among the top 100 in 21 of the 54 subjects assessed for the ranking, one more than the previous year, with eight subjects ranking in the top 50.

Earlier, the 2019 NTU Ranking of research output placed the U of A 81st in the world, up seven spots over the prior year. The advancement was bolstered by the university's 43rd-place performance in the subject of agricultural science, 47th in environment/ecology and 48th in electrical engineering.

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U of A ranked among world's top energy research universities - Folio - University of Alberta

Physiology

Does Diet And Gut Bacteria Contribute To Arteries Aging? – Anti Aging News

Recent research from University of Colorado Boulder researchers published in the American Heart Association journal Hypertension suggests that a compound produced in the gut when we eat red meat damages our arteries, and it may play a role in boosting the risk of developing heart disease as we get older.

The report also suggests that an individual may be able to prevent or even reverse this age related decline by making some simple dietary changes and implementing targeted therapies such as nutritional supplements.

Our work shows for the first time that not only is this compound directly impairing artery function, it may also help explain the damage to the cardiovascular system that naturally occurs with age, said first author Vienna Brunt, a postdoctoral researcher in the Department of Integrative Physiology.

When a person eats a portion of steak or a plate of scrambled eggs the resident gut bacteria immediate set to work at breaking it down, as they metabolize the amino acids L-carnitine and choline they churn out trimethylamine metabolic byproducts which the liver then converts into trimethylamine-N-Oxide, known as TMAO, and sends it coursing through the bloodstream.

Studies have shown that those with higher blood levels of TMAO are more than twice as likely to experience a heart attack or stroke, and those with higher blood levels of TMAO also tend to die earlier. However, scientists dont fully understand why.

This team set out to answer three questions drawing on both animal and human experiments: Does TMAO somehow damage the vascular system? If it does damage the vascular system how? And is it one of the reasons why cardiovascular health declines, even among those who dont smoke and exercise as they get older?

Blood and arterial health of 101 older adults and 22 young adults were measured, which revealed that TMAO levels significantly increase with age. This finding supports a previous mouse study showing the gut microbiome changes with age, breeding more bacteria that help to produce TMAO. Adults with higher levels of TMAO were found to have significantly worse artery function and showed greater signs of oxidative stress or tissue damage in the lining of their blood vessels.

When TMAO was fed directly to young mice their blood vessels aged rapidly. Just putting it in their diet made them look like old mice, said Brunt. She noted that 12-month-old mice (the equivalent of humans about 35 years old) looked more like 27-month-old mice (age 80 in people) after eating TMAO for several months.

Preliminary data suggest that mice with higher levels of TMAO also exhibit decreases in learning and memory, indicating that it may play a role in age related cognitive decline.

Older mice that ate dimethyl butanol were observed to experience their vascular dysfunction reverse; the team believes that this compound may prevent the production of TMAO. Dimethyl butanol can be found in olive oil, vinegar, and red wine in trace amounts.

The team notes that even a young vegan will produce some TMAO, but over time consuming a lot of animal products may take a toll on vascular health. The more red meat you eat, the more you are feeding those bacteria that produce it, said Brunt.

According to senior author Doug Seals who is the director of the Integrative Physiology of Aging Laboratory this study is an important breakthrough as it sheds new light in why the arteries erode with age, even within the seemingly healthiest of people.

Aging is the single greatest risk factor for cardiovascular disease, primarily as a result of oxidative stress to our arteries, said Seals. But what causes oxidative stress to develop in our arteries as we age? That has been the big unknown. This study identifies what could be a very important driver.

The team is further exploring possible compounds that may block the production of TMAO to prevent age related vascular decline. Until something is found perhaps it may be a good idea to skip that big steak or at least limit the intake of animal products to incorporate more plant based options, as the gut friendly plant based diet can help to reduce levels of TMAO as well.

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Does Diet And Gut Bacteria Contribute To Arteries Aging? - Anti Aging News

Physiology

A redox-active switch in fructosamine-3-kinases expands the regulatory repertoire of the protein kinase superfamily – Science

Kinase regulation conserved under stress

Oxidative stress is necessary for normal cellular function and tissue physiology but can also be pathological, and its effects are mediated in part through functional modification of various proteins. Shrestha et al. and Byrne et al. found that the oxidation of kinases at active siteadjacent cysteine residues, which were conserved across the eukaryotic kinome, regulated cell metabolism and mitosis. Shrestha et al. found that conserved cysteine residues within the diabetes-associated metabolic kinase FN3K acted as a toggle switch upon oxidation, promoting its functional oligomerization and consequently altering cellular redox status. Byrne et al. found that oxidation of mitotic kinases in human cells and yeast suppressed kinase catalytic activity and, in yeast, impaired cellular division. Exploring the effect of chronic oxidative stress on kinase function and how that may be spatiotemporally regulated may enable the development of new targeted therapeutics.

Aberrant regulation of metabolic kinases by altered redox homeostasis substantially contributes to aging and various diseases, such as diabetes. We found that the catalytic activity of a conserved family of fructosamine-3-kinases (FN3Ks), which are evolutionarily related to eukaryotic protein kinases, is regulated by redox-sensitive cysteine residues in the kinase domain. The crystal structure of the FN3K homolog from Arabidopsis thaliana revealed that it forms an unexpected strand-exchange dimer in which the ATP-binding P-loop and adjoining strands are swapped between two chains in the dimer. This dimeric configuration is characterized by strained interchain disulfide bonds that stabilize the P-loop in an extended conformation. Mutational analysis and solution studies confirmed that the strained disulfides function as redox switches to reversibly regulate the activity and dimerization of FN3K. Human FN3K, which contains an equivalent P-loop Cys, was also redox sensitive, whereas ancestral bacterial FN3K homologs, which lack a P-loop Cys, were not. Furthermore, CRISPR-mediated knockout of FN3K in human liver cancer cells altered the abundance of redox metabolites, including an increase in glutathione. We propose that redox regulation evolved in FN3K homologs in response to changing cellular redox conditions. Our findings provide insights into the origin and evolution of redox regulation in the protein kinase superfamily and may open new avenues for targeting human FN3K in diabetic complications.

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A redox-active switch in fructosamine-3-kinases expands the regulatory repertoire of the protein kinase superfamily - Science

Immunology

Navigating cytokine storms – Penn: Office of University Communications

How do you define cytokine storm and sepsis?

Hunter: The last time I had the flu, about 20 years ago, I had a fever, I felt like my bones were being crushed, and I thought I was going to die. That was not because the virus was replicating in my lungs and causing a huge amount of damage; it was that these soluble immune factors everywhere through my bodythese cytokineswere causing this whole-body shutdown and making everything feel terrible. Thats how people think about cytokine storms.

Everyone has cytokines circulating in their bodies; thats a normal part of the immune response. But when that response overshoots where it should be to clear an infection, thats where it becomes pathological and is considered a storm. And it doesnt have to be an infection that triggers it. It could be that something turns on a T cell by mistake, it could be an autoimmune response, or it could be a treatment that boosts the immune response to cure cancer.

Mangalmurti: Sepsis is now defined as an abnormal host response to a pathogen, whether its bacteria, virus, parasite, or fungi. Most people should be able to clear the pathogen and return to a normal state. Sepsis is a dysregulated response where there is not necessarily a return to normal. In sepsis, the response is often characterized by both a hyperinflammatory and an immunosuppressive response happening at the same time.

Hunter: A cytokine storm can be part of that. The question is, At what point does cytokine activation become pathological? Immunologists may talk about cytokine storms, but Im not sure we really understand why they make our muscles ache or cause a fever or respiratory distress or heart failure. Thats one of the things were trying to explain. Why does it feel like this? How does it amplify? Why do some people make an appropriate response to control infection and live while some overshoot and die?

A through-line of this work seems to be that the immune response isnt always either completely protective or completely harmful, but it can be somewhere in between?

Hunter: Yes, its all about balance. Of course, we know that an immune response can be protective, but there are also immune-mediated diseases. Everyone knows someone with an immune-mediated condition like arthritis, lupus, diabetes, and inflammatory bowel disease.

How have the two of you been working together?

Hunter: When Nilam and I first met I quickly realized my interests coincided with hers. I do basic immunology studying mice, while Nilams science is informed by her time in the ICU. Ive enjoyed getting her perspective on how disease works and the model infectious system that my laboratory uses. When Immunity asked us to write a primer for people who didnt really know what a cytokine storm was, we took that opportunity and ran with it.

Mangalmurti: A pandemic is never a good thing, but it has been a learning opportunity for all of us and a chance to bring together bench-based scientists with physicians and physician-scientists. We have a huge number of sepsis researchers on campus that dont necessary think theyre studying sepsis or dont contextualize their work that way.

A group of physicians and immunologists, including Chris and myself, started a joint sepsis working group so we could bring together scientists from many walks of life, so anyone from clinical epidemiology to fundamental basic scientists. The first meeting we had there were so many ideas flying back and forth about sepsis and pathogens and host response. It was exciting to see people from PSOM, the Childrens Hospital of Philadelphia, and Penn Vet so engaged.

Now with the pandemic, a focus on understanding the host response to infection is amplified and relevant to questions like why some people with COVID have no symptoms while others get hit really hard.

How is what were seeing with COVID-19 confirming or changing what we understand about cytokine storms and how to address them in patients?

Mangalmurti: Part of why I wanted to do this primer was to sort through this amazing amount of information about COVID that has been pouring in from Twitter, bioRxiv, and medRxiv and other places and try to make sense of it.

There was an opinion piece in the Lancet early on in the pandemic that everyone latched onto that suggested that specific therapies to tamp down cytokine storms were going to be beneficial for COVID. It was early in the pandemic, and this idea seemed to make sense. But we dont have rigorous evidence to back that up and, as we have learned more, we realized that it is not so simple.

In sepsis, multiple therapies to bock cytokine have been tried before, and there hasnt been any survival benefit. In fact, there has been some increased mortality, maybe because the drugs are not striking the right balance of immune response versus immune suppression or are not being used at the right time point in the infection.

One thing that was very clear to us after the first week of seeing COVID-19 patients was that most who came into the ICU with organ failure clearly had a condition that seemed to predispose them to vascular injury: obesity, diabetes, high blood pressure, age, a history of vascular disease, or clots. And that was striking because its not something we usually see in most other forms of sepsis, or other forms of acute respiratory distress syndrome.

That got us thinking about innate immunity in the vascular compartment and whether this virus had a penchant for the vasculature. Maybe theres a way to use what we know about this relationship with the vasculature to design and use more targeted anticytokine therapies.

Of course, when patients are doing poorly, clinicians are often desperate for a treatment. I understand that; we just need to remember to proceed with caution when were treating with drugs outside of a controlled trial.

Hunter: From my perspective its exciting to think about targeted therapies that are already available, like antibodies to cytokines that are already used in the clinic; maybe they could be repurposed and used in this setting. But we really need large clinical trials to assess whether our excitement about some of these approaches is meaningful and valid. Perhaps one consequence of the pandemic is that more people will be thinking about how to more effectively use cytokine therapies or cytokine neutralizing approaches, not just in COVID-19 but in sepsis in general. Sepsis is a disease where the advances in immunology have not yet had the same impact that they have in other conditions, such as cancer and autoimmunity.

Can the idea of a cytokine storm help explain the spectrum of responses weve seen to the coronavirus, from asymptomatic patients to those with severe disease?

Mangalmurti: There are certainly anecdotes from people who get this disease that they are home, theyre having fevers every night, they dont feel well. These people are having a cytokine storm, but it resolves, and they dont end up on a ventilator in the ICU. Maybe those patients dont have the predisposing factors that we talked about. It could also be that they have less of a viral load.

Hunter: No one is studying the asymptomatic patients. One question is, How asymptomatic are they really? Maybe they had a small fever one day; maybe that was their cytokine shower.Also, as Nilam mentioned, in every other system the amount of the virus you are exposed to matters, so Im not sure why it wouldnt matter here, too.

You wrote this primer hoping to reach an audience of immunologists. What do you hope they start doing or doing more of?

Hunter: We, the basic immunologists, need to be thinking more about the physiology of what were doing. Often, well look at immune cells in isolation. We need to look at their effects on the vascular system, the impact on lung function, the impact on heart function. In general, we need to realize that it is really important to understand a whole disease process, to look at the system more broadly.

Your work seems to underscore the value of collaboration across fields.

Hunter: Absolutely. Nilam has worked on sepsis and has been seeing sepsis patients for a long time. Shes dealing with really sick patients who have a lot going on. Basic scientists tend to want to simplify and reduce things. And youve got to meet somewhere in the middle, I think, for complex diseases. Penn is a really good place to do that, at PSOM, CHOP, and Penn Vet.

Mangalmurti: Im usually talking with clinicians about ARDS and sepsis, and now to partner with immunologists who are taking a deep dive into the cytokines, into the pathobiology of these things and looking more at the host-pathogen interface, its a really nice intersection. As awful as the pandemic has been, I hope some of our trainees will be intrigued by all these unanswered questions and want to learn more about disease processes.

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Navigating cytokine storms - Penn: Office of University Communications

Immunology

Humanigen Appoints Senior Executives to Management Team – BioSpace

BURLINGAME, Calif.--(BUSINESS WIRE)-- Humanigen, Inc., (HGEN) (Humanigen), a clinical stage biopharmaceutical company focused on preventing and treating cytokine release syndrome (CRS) with lenzilumab, the companys proprietary Humaneered anti-human granulocyte macrophage-colony stimulating factor (GM-CSF) monoclonal antibody, announced that several executives have been appointed to key positions at Humanigen.

Effective immediately, Dale Chappell, MD, MBA, has joined Humanigen to serve as its Chief Scientific Officer, David L. Tousley, CPA, MBA, has joined the company as Chief Accounting and Administrative Officer, Corporate Secretary and Treasurer, and Omar Ahmed, PharmD, has been promoted to the position of Senior Vice President, Clinical, Medical and Scientific Affairs. All three positions report to Cameron Durrant, MD, MBA, Chief Executive Officer, Humanigen.

Dr. Chappell began his career as a Howard Hughes Medical Institute fellow at the National Cancer Institute where he studied tumor immunology and published in the field of T-cell therapy, immunology pathways, and GM-CSF, giving him clear insights into the development and execution of our business strategy. He is also the founder of Black Horse Capital with decades of biotechnology investment experience.

Mr. Tousley has held roles including Executive Vice President and Chief Financial Officer and President and Chief Operating Officer at companies including Pasteur Merieux Connaught (now Sanofi Pasteur), AVAX Technologies, Inc. and DARA BioSciences. Mr. Tousley has led functions including finance and accounting, procurement, customer account management, strategic and financial planning and management, corporate governance, equity capital financing and business development, and raised in excess of $400 million in equity and debt financings in his career.

Dr. Ahmed has over 20 years of executive leadership experience building industry-leading specialty care portfolios, establishing strategic partnerships, and launching transformational blockbuster therapies. Dr. Ahmed held responsibilities for advancing Janssens $10 billion global immunology portfolio, from early development to late-stage development, including lifecycle management for Remicade, Simponi and Stelara and served as a board member for the Janssen EMEA Emerging Markets, covering 42 countries in the Middle East, West Asia and Africa Region. He also held leadership positons at Novartis and at Roche Pharmaceuticals.

We are pleased that both Dr. Chappell and Mr. Tousley, who have previously operated in interim capacities with the Company, have joined us as full-time members of the Humanigen team, stated Dr. Cameron Durrant. Their appointments, along with Dr. Ahmeds promotion, provide us with continuity and ongoing scientific and operational bench strength as we move the company forward. Filling these key leadership roles with proven executives who are highly regarded within the biotechnology sector, and who have been deeply involved with the strategic direction of our company, is a next step in our plan to rapidly grow into an organization committed to bringing important therapies to patients around the globe, Dr. Durrant concluded.

About Humanigen, Inc.

Humanigen, Inc. is developing its portfolio of clinical and pre-clinical therapies for the treatment of cancers and infectious diseases via its novel, cutting-edge GM-CSF neutralization and gene-knockout platforms. We believe that our GM-CSF neutralization and gene-editing platform technologies have the potential to reduce the inflammatory cascade associated with coronavirus infection. The companys immediate focus is to prevent or minimize the cytokine release syndrome that precedes severe lung dysfunction and ARDS in serious cases of SARS-CoV-2 infection. The company is also focused on creating next-generation combinatory gene-edited CAR-T therapies using strategies to improve efficacy while employing GM-CSF gene knockout technologies to control toxicity. In addition, the company is developing its own portfolio of proprietary first-in-class EphA3-CAR-T for various solid cancers and EMR1-CAR-T for various eosinophilic disorders. The company is also exploring the effectiveness of its GM-CSF neutralization technologies (either through the use of lenzilumab as a neutralizing antibody or through GM-CSF gene knockout) in combination with other CAR-T, bispecific or natural killer (NK) T cell engaging immunotherapy treatments to break the efficacy/toxicity linkage, including to prevent and/or treat graft-versus-host disease (GvHD) in patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT). Additionally, Humanigen and Kite, a Gilead Company, are evaluating lenzilumab in combination with Yescarta (axicabtagene ciloleucel) in patients with relapsed or refractory large B-cell lymphoma in a clinical collaboration. For more information, visit http://www.humanigen.com

Forward-Looking Statements

This release contains forward-looking statements. Forward-looking statements reflect management's current knowledge, assumptions, judgment and expectations regarding future performance or events. Although management believes that the expectations reflected in such statements are reasonable, they give no assurance that such expectations will prove to be correct and you should be aware that actual events or results may differ materially from those contained in the forward-looking statements. Words such as "will," "expect," "intend," "plan," "potential," "possible," "goals," "accelerate," "continue," and similar expressions identify forward-looking statements, including, without limitation, statements regarding our clinical and pre-clinical therapies and our development programs for them. Forward-looking statements are subject to a number of risks and uncertainties including, but not limited to our lack of profitability and need for additional capital; our dependence on partners to further the development of our product candidates; the uncertainties inherent in the development and launch of any new pharmaceutical product; the outcome of pending or future litigation; and the various risks and uncertainties described in the "Risk Factors" sections and elsewhere in the Company's periodic and other filings with the Securities and Exchange Commission.

All forward-looking statements are expressly qualified in their entirety by this cautionary notice. You should not place undue reliance on any forward-looking statements, which speak only as of the date of this release. We undertake no obligation to revise or update any forward-looking statements made in this press release to reflect events or circumstances after the date hereof or to reflect new information or the occurrence of unanticipated events, except as required by law.

View source version on businesswire.com: https://www.businesswire.com/news/home/20200707005282/en/

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Humanigen Appoints Senior Executives to Management Team - BioSpace

Immunology

Numab Therapeutics and Boehringer Ingelheim Enter into Collaboration to Develop Multi-specific Antibody Therapeutics for Cancer and Retinal Diseases |…

DetailsCategory: More NewsPublished on Tuesday, 07 July 2020 18:18Hits: 203

INGELHEIM, Germany & WAEDENSWIL, Switzerland I July 07, 2020 I Boehringer Ingelheim and Numab Therapeutics (Numab) today announced that they have entered into a research collaboration and worldwide licensing agreement. It will start with two projects aiming at novel therapies for difficult-to-treat lung and gastrointestinal (GI) cancers and patients with geographic atrophy (GA), a progressive, irreversible retinal disease that occurs in patients with age-related macular degeneration (AMD) for which there is no current treatment. The collaboration brings together Boehringer Ingelheims leading expertise in the research and development of life changing breakthrough therapies with Numabs multi-specific antibody platform.

Lung and GI cancers and retinal diseases are key focus areas of Boehringer Ingelheims research and development program. In oncology the company has built a broad and diverse pipeline, combining cancer immunology and cancer cell directed approaches. The novel T-cell engager to be developed with Numab adds to Boehringer Ingelheims growing cancer immunology portfolio and supports the strategy to take cancer on by targeting cold tumors with synergistic combination approaches. In retinal diseases Boehringer Ingelheim is pursuing a holistic approach leveraging existing expertise in oncology, inflammation, neurodegeneration, fibrosis and cardiometabolic diseases. The new GA program with Numab further broadens the companys comprehensive portfolio of next generation retinal therapy approaches in various stages of development up to Phase 2 in macular degeneration and diabetic retinal diseases.

We are thrilled to work with the excellent team at Numab to advance our portfolio assets. Numabs technology platform fits well with our internal antibody discovery and engineering capabilities and will enhance our efforts to deliver transformative antibody-based therapeutics to patients, said Paige Mahaney, SVP and US Discovery Research Site Head at Boehringer Ingelheim.

We are looking forward to working with Boehringer Ingelheim, a global leader in pharmaceutical R&D with profound expertise across a broad spectrum of therapeutic areas, further validating our technology platform. This addition to our growing roster of partnerships represents another key milestone in our business development efforts, commented Dr. Oliver Middendorp, Chief Business Officer of Numab Therapeutics. The upfront payment and near-term milestones attached to this alliance will further strengthen Numabs ability to accelerate the development of key proprietary assets.

Under the terms of the alliance, the partners will work together to discover one novel multi-specific antibody drug candidate in each area. Boehringer Ingelheim receives from Numab an exclusive worldwide license to develop and commercialize the resulting candidates in exchange for upfront and milestone payments, as well as tiered royalties on net sales of all products resulting from the alliance.

With todays announcement, Numab has been able to secure seven ongoing relationships with leading pharmaceutical companies including 3SBio / Sunshine Guojian, Boehringer Ingelheim, Eisai Co., Ltd., CStone Pharmaceuticals, Ono Pharmaceutical Co., Ltd., Kaken Pharmaceutical Co., Ltd., and Tillotts Pharma AG.

About Boehringer IngelheimMaking new and better medicines for humans and animals is at the heart of what we do. Our mission is to create breakthrough therapies that change lives. Since its founding in 1885, Boehringer Ingelheim is independent and family-owned. We have the freedom to pursue our long-term vision, looking ahead to identify the health challenges of the future and targeting those areas of need where we can do the most good.

As a world-leading, research-driven pharmaceutical company, more than 51,000 employees create value through innovation daily for our three business areas: Human Pharma, Animal Health, and Biopharmaceutical Contract Manufacturing. In 2019, Boehringer Ingelheim achieved net sales of19 billion euros. Our significant investment of almost 3.5 billion euros in R&D drives innovation, enabling the next generation of medicines that save lives and improve quality of life.

We realize more scientific opportunities by embracing the power of partnership and diversity of experts across the life-science community. By working together, we accelerate the delivery of the next medical breakthrough that will transform the lives of patients now, and in generations to come.

More information about Boehringer Ingelheim can be found at http://www.boehringer-ingelheim.com or in our annual report http://annualreport.boehringer-ingelheim.com.

About Numab TherapeuticsNumab Therapeutics is an oncology-focused biopharmaceutical company based in Zurich-area, Switzerland. At Numab, we are writing the next chapter in cancer immunotherapy by creating multi-specific antibodies that enable the pursuit of novel therapeutic strategies. With our proprietary MATCH technology platform, we are fueling a new wave of multi-specific drug candidates engineered with versatility and developability in mind. Our lead product was designed to balance potent anti-tumor immunity with a desirable safety profile by targeting 4-1BB, PD-L1 and Human Serum Albumin simultaneously. We believe meeting the highest quality standards in every step of the drug design process matters and will result in better patient outcomes. For further information, visit http://www.numab.com (link is external).

SOURCE: Numab Therapeutics

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Immunology

UCB and Ferring Pharmaceuticals Announce Co-Promotion of CIMZIA (certolizumab pegol) for the Treatment of Adults with Moderate to Severe Crohn’s…

ATLANTA and PARSIPPANY, N.J., July 7, 2020 /PRNewswire/ -- UCB and Ferring Pharmaceuticals Inc. today announced they have entered into a co-promotion agreement to commercialize the prefilled syringe formulation of CIMZIA® (certolizumab pegol) in the United States, specifically for the treatment of Crohn's disease (CD). Ferring will take over marketing, sales promotion, and field medical affairs activities. UCB will continue to be responsible for all product-related activities, including revenue recognition. CIMZIA is an injectable biologic treatment option for adults with moderate to severe Crohn's disease with inadequate response to conventional therapy. UCB will continue to promote and to commercialize the lyophilized formulation of CIMZIA for all indications as well as the prefilled syringe formulation for CIMZIA's rheumatology and dermatology indications.

"UCB is committed to serving the needs of immunology patients, including those living with Crohn's disease. We are excited about this opportunity as it will expand the awareness to the benefits of CIMZIA for individuals living with moderate to severe Crohn's disease, while continuing to support patients through our services and programs," said Camille Lee, Head of U.S. Immunology at UCB. "We believe UCB and Ferring are a strategic fit for the co-promotion as both companies have a strong patient-focused commitment and Ferring has expertise in gastroenterology. UCB is preparing for future launches in immunology, demonstrating our commitment to patients with severe chronic diseases."

This co-promotion allows Ferring to expand its growing portfolio in the gastrointestinal space and support patients living with Crohn's disease, while enabling UCB to focus on and prepare for the future.

"Ferring is focusing on gut health as we expand our gastroenterology portfolio," said Brent Ragans, President of Ferring US. "Together with our existing portfolio, this agreement with UCB will allow Ferring to offer treatment options to the nearly 800,000 adult patients in the U.S. who suffer from Crohn's disease."

CIMZIA has been a treatment option for adults living with moderate to severe Crohn's disease over the last 12 years, since it was approved by the FDA in 2008 based on safety and efficacy data from clinical trials in more than 1,500 patients with Crohn's disease.

CIMZIA can be administered either through self-injection or by a healthcare professional.1 CIMZIA can lower the ability to fight infections. Some people who received CIMZIA have developed serious infections, including tuberculosis (TB) and infections caused by viruses, fungi, or bacteria that have spread throughout the body.1 Some of these serious infections have caused hospitalization and death.1

About Crohn's disease

Crohn's disease is an inflammatory bowel disease causing chronic inflammation of the gastrointestinal (GI) tract.2 Crohn's disease can affect any part of the GI tract from mouth to anus, most commonly involving the ileum and proximal colon.3 It belongs to a group of conditions known as inflammatory bowel diseases, or IBD.4 The disease can occur at any age, but is most often diagnosed in adolescents and adults between the ages of 20 and 30.2 Approximately 780,000 Americans are currently affected by Crohn's disease.3

Patients with Crohn's disease may present acutely or have a history of symptoms prior to confirming diagnosis.4 A hallmark symptom in patients with Crohn's disease is abdominal pain.4 Other symptoms include diarrhea potentially persistent in nature,GI bleeding, urgent need to move bowels,abdominal cramps,sensation of incomplete bowel evacuationand constipation, which can lead to bowel obstruction.4

About CIMZIA® in the US

CIMZIA is the only Fc-free, PEGylated anti-TNF (Tumor Necrosis Factor). CIMZIA has a high affinity for human TNF-alpha, selectively neutralizing the pathophysiological effects of TNF-alpha.

CIMZIA is indicated for reducing signs and symptoms of Crohn's disease (CD) and maintaining clinical response in adult patients with moderately to severely active disease who have had an inadequate response to conventional therapy.

CIMZIA is also indicated for the treatment of adults with moderately to severely active rheumatoid arthritis (RA), adults with active psoriatic arthritis (PsA), adults with active ankylosing spondylitis (AS), and adults with active non-radiographic axial spondyloarthritis (nr-axSpA) with objective signs of inflammation.

In addition, CIMZIA is indicated for the treatment of moderate to severe plaque psoriasis (PSO) in adults who are candidates for systemic therapy or phototherapy. See important safety information including risk of serious bacterial, viral and fungal infections and tuberculosis below.

IMPORTANT SAFETY INFORMATION about CIMZIA in the U.S.

CONTRAINDICATIONS

CIMZIA is contraindicated in patients with a history of hypersensitivity reaction to certolizumab pegol or to any of the excipients. Reactions have included angioedema, anaphylaxis, serum sickness, and urticaria.

SERIOUS INFECTIONS

Patients treated with CIMZIA are at increased risk for developing serious infections that may lead to hospitalization or death. Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids.

Discontinue CIMZIA if a patient develops a serious infection or sepsis.

Reported infections include:

Carefully consider the risks and benefits of treatment with CIMZIA prior to initiating therapy in the following patients: with chronic or recurrent infection; who have been exposed to TB; with a history of opportunistic infection; who resided in or traveled in regions where mycoses are endemic; with underlying conditions that may predispose them to infection. Monitor patients closely for the development of signs and symptoms of infection during and after treatment with CIMZIA, including the possible development of TB in patients who tested negative for latent TB infection prior to initiating therapy.

MALIGNANCY

Lymphoma and other malignancies, some fatal, have been reported in children and adolescent patients treated with TNF blockers, of which CIMZIA is a member. CIMZIA is not indicated for use in pediatric patients.

HEART FAILURE

HYPERSENSITIVITY

HEPATITIS B VIRUS REACTIVATION

NEUROLOGIC REACTIONS

HEMATOLOGIC REACTIONS

DRUG INTERACTIONS

AUTOIMMUNITY

IMMUNIZATIONS

ADVERSE REACTIONS

For full prescribing information, please visit https://ucb-usa.com/_up/ucb_usa_com_kopie/documents/Cimzia_PI.pdf

References:

CIMZIA® is a registered trademark of the UCB Group of Companies.

For further information, Ferring Pharmaceuticals:

Heather Guzzi Director, Brand Communications (862) 286-5254 (direct) (973) 769-3999 (mobile) heather.guzzi@ferring.com

For further information, UCB: U.S. Communications Allyson Funk Communications, U.S. T. 770.970.8338, allyson.funk@ucb.com

Investor Relations Antje Witte Investor Relations, UCB T +32.2.559.94.14, antje.witte@ucb.com

Isabelle Ghellynck Investor Relations, UCB T+32.2.559.9588, isabelle.ghellynck@ucb.com

About UCB UCB, Brussels, Belgium (www.ucb.com) is a global biopharmaceutical company focused on the discovery and development of innovative medicines and solutions to transform the lives of people living with severe diseases of the immune system or of the central nervous system. With more than 7 600 people in approximately 40 countries, the company generated revenue of 4.9 billion in 2019. UCB is listed on Euronext Brussels (symbol: UCB). Follow us on Twitter: @UCBUSA

About Ferring Pharmaceuticals Ferring Pharmaceuticals is a research-driven, specialty biopharmaceutical group committed to helping people around the world build families and live better lives. In the United States, Ferring is a leader in reproductive medicine and maternal health, and in specialty areas within gastroenterology and orthopaedics. For more information, call 1-888-FERRING (1-888-337-7464); visit http://www.FerringUSA.com

Forward looking statements UCB This press release may contain forward-looking statements including, without limitation, statements containing the words "believes", "anticipates", "expects", "intends", "plans", "seeks", "estimates", "may", "will", "continue" and similar expressions. These forward-looking statements are based on current plans, estimates and beliefs of management. All statements, other than statements of historical facts, are statements that could be deemed forward-looking statements, including estimates of revenues, operating margins, capital expenditures, cash, other financial information, expected legal, arbitration, political, regulatory or clinical results or practices and other such estimates and results. By their nature, such forward-looking statements are not guarantees of future performance and are subject to known and unknown risks, uncertainties and assumptions which might cause the actual results, financial condition, performance or achievements of UCB, or industry results, to differ materially from those that may be expressed or implied by such forward-looking statements contained in this press release. Important factors that could result in such differences include: the global spread and impact of COVID-19, changes in general economic, business and competitive conditions, the inability to obtain necessary regulatory approvals or to obtain them on acceptable terms or within expected timing, costs associated with research and development, changes in the prospects for products in the pipeline or under development by UCB, effects of future judicial decisions or governmental investigations, safety, quality, data integrity or manufacturing issues; potential or actual data security and data privacy breaches, or disruptions of our information technology systems, product liability claims, challenges to patent protection for products or product candidates, competition from other products including biosimilars, changes in laws or regulations, exchange rate fluctuations, changes or uncertainties in tax laws or the administration of such laws, and hiring and retention of its employees. There is no guarantee that new product candidates will be discovered or identified in the pipeline, will progress to product approval or that new indications for existing products will be developed and approved. Movement from concept to commercial product is uncertain; preclinical results do not guarantee safety and efficacy of product candidates in humans. So far, the complexity of the human body cannot be reproduced in computer models, cell culture systems or animal models. The length of the timing to complete clinical trials and to get regulatory approval for product marketing has varied in the past and UCB expects similar unpredictability going forward. Products or potential products which are the subject of partnerships, joint ventures or licensing collaborations may be subject to differences disputes between the partners or may prove to be not as safe, effective or commercially successful as UCB may have believed at the start of such partnership. UCB's efforts to acquire other products or companies and to integrate the operations of such acquired companies may not be as successful as UCB may have believed at the moment of acquisition. Also, UCB or others could discover safety, side effects or manufacturing problems with its products and/or devices after they are marketed. The discovery of significant problems with a product similar to one of UCB's products that implicate an entire class of products may have a material adverse effect on sales of the entire class of affected products. Moreover, sales may be impacted by international and domestic trends toward managed care and health care cost containment, including pricing pressure, political and public scrutiny, customer and prescriber patterns or practices, and the reimbursement policies imposed by third-party payers as well as legislation affecting biopharmaceutical pricing and reimbursement activities and outcomes. Finally, a breakdown, cyberattack or information security breach could compromise the confidentiality, integrity and availability of UCB's data and systems.

Given these uncertainties, you should not place undue reliance on any of such forward-looking statements. There can be no guarantee that the investigational or approved products described in this press release will be submitted or approved for sale or for any additional indications or labelling in any market, or at any particular time, nor can there be any guarantee that such products will be or will continue to be commercially successful in the future.

UCB is providing this information, including forward-looking statements, only as of the date of this press release and it does not reflect any potential impact from the evolving COVID-19 pandemic, unless indicated otherwise. UCB is following the worldwide developments diligently to assess the financial significance of this pandemic to UCB. UCB expressly disclaims any duty to update any information contained in this press release, either to confirm the actual results or to report or reflect any change in its forward-looking statements with regard thereto or any change in events, conditions or circumstances on which any such statement is based, unless such statement is required pursuant to applicable laws and regulations.

Additionally, information contained in this document shall not constitute an offer to sell or the solicitation of an offer to buy any securities, nor shall there be any offer, solicitation or sale of securities in any jurisdiction in which such offer, solicitation or sale would be unlawful prior to the registration or qualification under the securities laws of such jurisdiction.

USP-CZ-CD-2000038

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Immunology

Allogene Therapeutics Adds Immunotherapy Luminaries, Thomas F. Gajewski, MD, Ph.D., and Stephan Grupp, MD, Ph.D., to its Scientific Advisory Board -…

SOUTH SAN FRANCISCO, Calif., July 07, 2020 (GLOBE NEWSWIRE) -- Allogene Therapeutics Inc. (Nasdaq: ALLO), a clinical-stage biotechnology company pioneering the development of allogeneic CAR T (AlloCAR T) therapies for cancer, today announced the appointment ofThomas F. Gajewski, M.D., Ph.D., and Stephan Grupp, M.D., Ph.D. to itsScientific Advisory Board(SAB).The SAB comprises experts across oncology, immunology, cell therapy, and drug discovery and development.

We areprivileged to welcome Drs. Gajewski and Grupp to our Scientific Advisory Board, saidRafael Amado, M.D., Executive Vice President of Research & Development and Chief Medical Officer of Allogene. The additions of Dr. Gajewski and Dr. Grupp further enhance what has become one of the most distinguished cell therapy SABs in the industry and is an important component of our strategy to lead the development of allogeneic cell therapies today and tomorrow.

New Allogene SAB members:

The new advisors join existing SAB members, Chairman Ton Schumacher, Ph.D.,Donald B. Kohn, M.D., Malcolm K. Brenner, M.D., Ph.D.,Matthew Porteus, M.D., Ph.D., Owen Witte, M.D., Stephen J. Forman, M.D., and Wendell Lim, Ph.D.

About Allogene TherapeuticsAllogene Therapeutics, with headquarters inSouth San Francisco, is a clinical-stagebiotechnology company pioneering the development of allogeneic chimeric antigen receptor Tcell (AlloCAR T) therapies for cancer. Led by a management team with significantexperience in cell therapy, Allogene is developing a pipeline of off-the-shelf CAR T cell therapycandidates with the goal of delivering readily available cell therapy on-demand, more reliably, and atgreater scale to more patients. For more information, please visitwww.allogene.com, and follow @AllogeneTx on Twitter and LinkedIn.

Cautionary Note on Forward-Looking Statements for Allogene This press release contains forward-looking statements for purposes of the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. The press release may, in some cases, use terms such as "predicts," "believes," "potential," "proposed," "continue," "estimates," "anticipates," "expects," "plans," "intends," "may," "could," "might," "will," "should" or other words that convey uncertainty of future events or outcomes to identify these forward-looking statements. Forward-looking statements include statements regarding intentions, beliefs, projections, outlook, analyses or current expectations concerning, among other things: the ability to develop allogeneic CAR T therapies for cancer and the potential benefits of AlloCAR T therapy. Various factors may cause differences between Allogenes expectations and actual results as discussed in greater detail in Allogenes filings with the SEC, including without limitation in its Form 10-Q for the quarter ended March 31, 2020. Any forward-looking statements that are made in this press release speak only as of the date of this press release. Allogene assumes no obligation to update the forward-looking statements whether as a result of new information, future events or otherwise, after the date of this press release.

Kymriah is a registered trademark of Novartis Pharmaceuticals Corporation.AlloCAR T is a trademark of Allogene Therapeutics, Inc.

Allogene Media/Investor Contact:Christine CassianoChief Communications Officer(714) 552-0326Christine.Cassiano@allogene.com

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Allogene Therapeutics Adds Immunotherapy Luminaries, Thomas F. Gajewski, MD, Ph.D., and Stephan Grupp, MD, Ph.D., to its Scientific Advisory Board -...