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Coronavirus Today: Who’s dying of COVID-19 now? – Los Angeles Times

Posted: September 25, 2022 at 2:35 am

Good evening. Im Karen Kaplan, and its Tuesday, Sept. 20. Heres the latest on whats happening with the coronavirus in California and beyond.

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People arent dying of COVID anymore.

It may seem that way, especially when President Biden disses masks on 60 Minutes and tells a national TV audience that the pandemic is over.

But when a friend made that observation to Erick Morales recently, he begged to differ.

Morales own mother, Alejandra Gutirrez, died of COVID-19 in June at the age of 59.

Gutirrez was vaccinated and boosted. She was careful, and so were her adult children, who wore masks when they were with her and avoided social situations that might result in a coronavirus exposure.

But Gutirrez was unlucky. She came down with ovarian cancer during the first pandemic winter, and despite multiple treatments, it spread to her brain in January.

The cancer weakened her, but it wasnt what killed her. She caught COVID-19 in late May and struggled to breathe. In her final days, she lost the ability to speak.

Gutirrez was one of the more than 400 people who died of COVID-19 each day in the U.S. during June, July and August, according to data from the Johns Hopkins Coronavirus Resource Center. Even now, with the second Omicron wave ebbing, COVID-19 is still killing an average of 425 Americans per day, the center reports.

In January 2021, when the first COVID-19 vaccines were being rolled out, the countrys daily death toll exceeded 3,300. A number like 425 is a definite improvement. But its a lot higher than the handful of cases many of us presume it to be.

For the record:

10:41 p.m. Sept. 21, 2022A previous version of this newsletter said that in January 2021, the countrys daily COVID-19 death toll exceeded 23,000. That was the weekly death toll, which averaged out to more than 3,300 deaths per day.

In fact, COVID-19 is still one of the countrys leading causes of death. As of Tuesday, it would rank fifth, between strokes (439 deaths per day) and chronic lower respiratory diseases (418 deaths per day).

If that seems hard to believe, how about this: In Los Angeles County alone, nearly 800 people died of COVID-19 between May and July. Thats roughly 60% higher than during the same three months last year, when the county recorded nearly 500 deaths.

At a time when vaccines, boosters, medications and antibody treatments are plentiful, when hospitals have the bandwidth to care for patients who are seriously ill, and when, as White House COVID-19 Response Coordinator Dr. Ashish Jha said, most COVID-19 deaths are preventable, youve got to wonder: Who is dying of COVID-19 now?

My colleagues Emily Alpert Reyes and Aida Ylanan have the answer.

It turns out that Gutirrez was a something of an anomaly. Recent COVID-19 deaths have been heavily concentrated among senior citizens.

Alejandra Morales-Gutirrez and brother Erick Morales lost their mother, Alejandra Gutirrez, to COVID-19 in June.

(Christina House / Los Angeles Times)

In California, about half of those who died this summer were at least 80 years old. Another third were people between the ages of 65 and 79.

Throughout California, Black residents had the highest COVID-19 death rate, pretty much regardless of age. And in L.A. County, men have been more likely to die than women.

Gutirrez was a typical COVID-19 victim in one respect: She already had a health problem that made her vulnerable to a serious case of COVID-19. For people like her, an encounter with the coronavirus can be like dry brush encountering a lit match, said Michael T. Osterholm, director of the Center for Infectious Disease Research and Policy at the University of Minnesota.

It doesnt cause the high temperatures, or the winds, or the low humidity, he said. But nothing happens until you throw that SARS-CoV-2 virus into the mix.

Here in L.A. County, nearly half of the people who died of COVID-19 between May and July were contending with at least three health conditions before the coronavirus came along, and almost all had at least one. Those conditions werent necessarily as serious as ovarian cancer; typical examples include obesity, diabetes, high blood pressure and cardiovascular disease.

In addition, residents of poorer neighborhoods were more likely to die of COVID-19 than residents of wealthier ones.

But COVID-19 can kill anyone. In recent months, hundreds of young and middle-aged adults have died of the disease, as have four minors. And so have 412 Californians over the age of 12 who were vaccinated (including 260 who were also boosted), although they represent less than 0.01% of state residents whove gotten the shots.

The Omicron variant especially the BA.5 subvariant has been infecting so many people that youve surely encountered tons of people whove recently recovered from a bout with COVID-19. More than in years past, it probably feels like COVID-19 survivors are everywhere. And they are.

But the number of infections is so high that even with a low mortality rate, the death count is still substantial. Its just that in a country eager to move on from the pandemic and stop thinking about things such as masks and booster shots, these deaths arent getting the attention they deserve.

The elderly, the immunocompromised, and the unvaccinated or under-vaccinated they are the ones that account for the vast majority of deaths due to COVID-19, said Dr. Thomas Yadegar, medical director of the intensive care unit at Providence Cedars-Sinai Tarzana Medical Center.

Weve sacrificed the lives of our most vulnerable for our own convenience, he said.

California cases and deaths as of 4:55 p.m. on Tuesday:

Track Californias coronavirus spread and vaccination efforts including the latest numbers and how they break down with our graphics.

Its no secret that the United States had a less-than-textbook response to the COVID-19 pandemic. It turns out we had plenty of company, even among wealthy nations that were expected to be more prepared.

So says a group of experts convened by the medical journal Lancet. In a report released last week, they made it abundantly clear that they were not impressed with the worlds efforts to rise to the occasion.

The Institute for Health Metrics and Evaluation estimates the pandemics global death toll at around 17.2 million, a staggering figure that is both a profound tragedy and a massive global failure at multiple levels, the members of the Lancet COVID-19 Commission wrote.

And theres plenty of blame to go around, they added: Too many governments have failed to adhere to basic norms of institutional rationality and transparency, too many people often influenced by misinformation have disrespected and protested against basic public health precautions, and the worlds major powers have failed to collaborate to control the pandemic.

That failure to collaborate came in many forms, the commission members wrote. It started with Chinas delay in notifying the world about the patients in Wuhan who had come down with a mysterious type of pneumonia that wasnt caused by any known virus. It continued with multiple countries failure to coordinate their efforts to contain and suppress the novel virus, or to figure out what those efforts ought to entail.

Wealthy countries didnt do enough to ensure that low- and middle-income countries had the money they needed to procure personal protective equipment, ventilators, test kits and other necessary supplies. And when there were limited supplies of medicines and vaccines, rich nations did not share equally with poor ones, the report says.

Countries did not gather timely, accurate, and systematic data on infections, deaths, viral variants and other factors that would be important to know if you wanted to get a pandemic under control, the experts wrote.

The World Health Organization didnt want to get ahead of the science with good reason but it took too long to acknowledge that people with asymptomatic infections could spread the coronavirus without realizing it, and that the virus spreads mainly through the air. As a result, the WHO was slow to advocate policy responses commensurate with the actual dangers of the virus, the report says.

And no one at any level has had much success combating the extensive misinformation and disinformation campaigns on social media, the report adds.

Thats not even a complete list of the problems the Lancet commission identified.

The commission was established in July 2020 with the aim of finding ways to help countries work together more effectively. Its 28 members are experts in disciplines such as epidemiology, vaccinology, economics and public policy.

Right off the bat, the report explains that you cant suppress an infectious disease without prosociality, which means prioritizing the good of society as a whole over the interests of individuals. Unfortunately, the growing gap between the haves and have-nots in many countries has undermined any sense of collective purpose.

In the U.S. and other countries, an unwillingness to put the interests of society as a whole ahead of the interests of individuals has undermined efforts to get the pandemic under control, experts say.

(Cedar Attanasio / Associated Press)

In the United States and elsewhere, false claims about COVID-19 vaccines and debunked treatments such as ivermectin, among other things, were spread by politicians and cable television personalities for the sake of partisanship, not public health. In the U.S. alone, unfounded anti-vaccine sentiment has led to as many as 200,000 preventable deaths, and this anti-science movement has globalised with tragic consequences, the commission wrote.

We cant go back in time and do everything over. But the commission offered advice on where to go from here.

For starters, it said its not too late for countries to get serious about the basics, including mass vaccination, accessible testing, and treatment. They should be accompanied by policies that support people who need to isolate, as well as common-sense preventive measures such as mask mandates in certain settings. Most importantly, the commission wrote, these efforts should be implemented on a sustainable basis, rather than as a reactive policy that is abruptly turned on and off.

To make sure the pandemic ends as quickly as possible, countries should work together to track new coronavirus variants and quickly assess the risks they pose.

To be better prepared for the next pandemic threat, the commission advised countries to strengthen their own health systems and make sure everyone has access to medical care. In addition, they should shore up their disease surveillance and reporting systems, emphasize the importance of preventive health and emergency preparedness, improve their public health communication strategies, and more aggressively fight health disinformation, according to the report.

Countries should invest a lot more in the World Health Organization and come up with better ways to cooperate and coordinate and they should do it now so theyll be ready when the next infectious disease threat inevitably arises.

That said, countries need to work harder to prevent that next outbreak from happening, the commission said. That means they should come up with more uniform rules about the trade of both domestic and wild animals, and make sure theyre enforced. They should also give the WHO more authority to keep tabs on research programs involving dangerous pathogens to make sure that biosafety rules are followed.

Whether anyone will follow this advice remains to be seen. The commission didnt exactly strike an optimistic tone as it wrapped up its report:

The lack of ambition in the global response to COVID-19 is like that of other pressing global challenges, such as the climate emergency; the loss of global biodiversity; the pollution of air, land, and water; the persistence of extreme poverty in the midst of plenty; and the large-scale displacement of people as a result of conflicts, poverty, and environmental stress.

See the latest on Californias vaccination progress with our tracker.

Another pandemic precaution has bit the dust: As of Saturday, California no longer requires unvaccinated workers at healthcare facilities, schools and other congregate settings to get tested for coronavirus infections once a week.

Those weekly surveillance tests used to be an important part of the states pandemic response. But considering where we are in the outbreak, the tests arent nearly as useful as they once were.

Most state residents now have some immunity through vaccination or a past infection or both so they face less risk of becoming seriously ill. Plus, the Omicron subvariants spread so quickly that weekly testing isnt enough to slow it down, said Dr. Toms Aragn, director of the California Department of Public Health.

Los Angeles County may drop one of its rules by the end of the month if coronavirus case rates continue to decline. If the county sees fewer than 100 cases a week per 100,000 residents roughly 1,400 cases per day masks will no longer be required on public transportation or in hubs such as airports and train stations.

As of Tuesday, the county was averaging 1,735 cases per day over the last week, according to The Times tracker. County Public Health Director Barbara Ferrer said we could hit the lower threshold by the end of the month.

Should that happen, the county would also stop recommending that everyone wear a mask indoors in public settings such as grocery stores and offices. Face coverings would still be strongly recommended in high-risk settings for people who are older, unvaccinated, live in high-poverty areas or have health conditions that make them more susceptible to a severe case of COVID-19. Otherwise, the decision about covering up would be a matter of personal preference.

Masks will continue to be required in healthcare settings, correctional facilities, cooling centers and a handful of other places.

California isnt the only place seeing pandemic improvements. The World Health Organization says the number of new infections is dropping in every part of the globe.

The WHOs latest weekly report counted 3.1 million new cases, a 28% drop from the previous week. Deaths also fell by 22%, to just over 11,000 the lowest worldwide death toll since March 2020.

We are not there yet, but the end is in sight, WHO Director-General Tedros Adhanom Ghebreyesus said Wednesday.

Dr. Anthony Fauci, the top infectious disease expert in the U.S., agreed Monday that were heading in that direction. But unlike Biden, he walked back Bidens assessment that the pandemic phase of the outbreak was already behind us.

It is likely that we will see another variant emerge in the late fall or winter, Fauci said Monday during a talk at the Center for Strategic and International Studies in Washington.

Dr. Eric Topol, a professor of molecular medicine at Scripps Research in La Jolla, schooled the president as well.

We all wish that were true, Topol wrote in an an op-ed. But unfortunately, that is a fantasy right now. All the data tell us the virus is not contained. Far too many people are dying and suffering. And new, worrisome variants are on the horizon.

An experimental vaccine may help us stay ahead of those new variants. Instead of focusing solely on the spike protein, which has proved adept at mutating in ways that reduce vaccine effectiveness, the new shots also target a far more stable nucleocapsid protein.

Although the vaccines design was based on an early coronavirus strain first seen in Wuhan, it was effective against both the Delta and Omicron variants and when tested in mice and hamsters. Its still several steps away from being tested in humans, but scientists are optimistic that it could lead the way to a one-size-fits-all vaccine that provides lasting protection without needing to be tweaked on a regular basis like the flu shot.

Its a great idea, said Dr. Paul Offit, a virologist and immunologist at the University of Pennsylvania who wasnt involved in the research. You could have argued that we should have done this at the beginning.

And finally, the Chinese government is facing more complaints about its zero-COVID strategy. Earlier this month it was a magnitude 6.8 earthquake in Sichuan province that triggered protests because millions of residents in lockdown were prevented from fleeing their seriously damaged homes.

This week it was a fatal bus crash in the middle of the night in Guizhou province. Forty-seven passengers were being transported to a quarantine facility outside the capital city, Guiyang; 27 of them died.

Critics went online and accused the government of moving the passengers for political purposes, not public health ones. They speculated that residents were being taken outside the city limits so Guiyang wouldnt have to report any new illnesses.

Will this ever end? one commenter asked. Is there scientific validity to hauling people to quarantine, one car after another?

In addition, residents in some neighborhoods complained of hunger after food deliveries were missed, a mistake local officials attributed to their lack of experience and inappropriate methods. The local zoo worried it would run out of food for its animals and appealed to the public for donations of pork, chicken, apples, watermelons, carrots and other produce.

Food shortages are also a problem in Ghulja, a city in Chinas far western Xinjiang region where the Uyghur population is used to harsh treatment from the government.

After more than 40 days of lockdown, hungry and frustrated residents went online to share videos of empty refrigerators and feverish children. In some cases, people who have ingredients to make bread havent been able to bake their dough because authorities wont let them go outside to use their backyard ovens.

Nyrola Elima, Uyghur from Ghulja who no longer lives there, told the Associated Press that her father was sharing one tomato each day with his 93-year-old mother, and that her aunt was desperate for milk for her toddler grandson. Her account could not be independently verified, but her descriptions were in line with videos posted by others.

Chinese censors worked to remove those posts from social media, though some reappeared. Six people were arrested for spreading rumors about the lockdown.

Todays question comes from readers who want to know: Whats the difference between being fully vaccinated and being up to date?

The CDC considers someone to be fully vaccinated if theyve finished their primary series of COVID-19 shots. For Comirnaty (the vaccine from Pfizer and BioNTech), Spikevax (the one from Moderna) and the (relatively) new offering from Novavax, that means two shots given between three and eight weeks apart. Only a single dose is required for the Johnson & Johnson vaccine.

But immunity wanes and new variants spark fresh COVID-19 surges. That means being fully vaccinated is just the beginning.

The immune system needs a refresher course from time to time, and a booster shot provides one. But rather than change the definition of fully vaccinated, the CDC instead said people who got the boosters recommended for them were up to date with their vaccinations.

If youre at least 12 years old, that means getting a new bivalent booster shot to (hopefully) bolster your protection against BA.4 and BA.5. To be eligible, you must be fully vaccinated and not have had a COVID-19 vaccine in at least two months or a coronavirus infection in at least three months. Once you get a bivalent booster, youll be considered up to date regardless of how many booster shots youve had (or missed) in the past.

We want to hear from you. Email us your coronavirus questions, and well do our best to answer them. Wondering if your questions already been answered? Check out our archive here.

(Allen J. Schaben / Los Angeles Times)

The woman at Hermosa Beach in the picture above is Sandhya Kambhampati, a colleague of mine on the Data Desk. She caught COVID-19 very early in the pandemic, then became one of the first long COVID patients her doctors had encountered. Last year, she wrote a first-person account of what it took to convince them her symptoms were real.

They finally came around, but Kambhampati still struggled. Eventually, at her doctors insistence, she took a leave from work so she could focus on healing. Painting became an integral part of that process.

At first, it offered an escape on my worst days, but over the last few months, it has developed into much more, she writes in a new essay. Painting sunsets at the beach is simultaneously calming and energizing, allowing her to recharge her batteries and help others who are just starting their journeys with long COVID.

Painting gives me a place to release the medical trauma that people share with me and keep going, she writes.

You may not be dealing with long COVID, but you can follow Kambhampatis lead and shift your mind-set for the better.

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Home | Department of Animal Science

Posted: September 25, 2022 at 2:34 am

Message from the Department Head

Animal Science was one of the first disciplines taught at the University of Connecticut, established as the historical Storrs Agricultural School in 1881. Today the Department of Animal Science is the home of more than 400 undergraduate students (both 2-year and 4-year programs) as well as dozens of graduate students pursuing advanced degrees. The Department offers ample hands-on learning and student employment opportunities with a total of 1,000+ dairy and beef cattle, sheep, chickens, pigs, and horses all within minutes of walking distance on campus.

The Department's faculty are accomplished educators and scientists for winning university, regional and national teaching and research awards, for publishing in international scientific journals and for serving as leaders in professional societies. Together, they cover the diverse areas of animal genetics/genomics, breeding, biotechnology (genetic engineering and stem cells), animal reproduction, embryology, growth biology and endocrinology, food microbiology and safety, dairy technology and safety, equine science, dairy production and management, meat chemistry, laboratory animal science as well as diversified livestock.

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T-Cell Therapy Delays Disease Progression for People With Advanced Melanoma – Cancer Health Treatment News

Posted: September 25, 2022 at 2:31 am

Personalized treatment for advanced melanoma using tumor-infiltrating lymphocytes (TILs)T cells with a proven ability to recognize and fight cancerreduced the risk of disease progression or death compared with checkpoint inhibitor immunotherapy, according to research presented at the European Society for Medical Oncology (ESMO) Congress 2022.

This study shows for the first time in a randomized, controlled trial that cell therapy can be efficacious and beneficial for patients with solid cancers, lead investigator John Haanen, MD, of the Netherlands Cancer Institute in Amsterdam, said in an ESMO press release. For patients with melanoma, we see a 50% reduction in the chance of progression of the disease or dying from the disease, which is absolutely practice changing.

Melanoma is among the malignancies most susceptible to immunotherapy, treatment that helps the immune system fight cancer. Standard therapy for advanced melanoma may include the PD-1 checkpoint inhibitors Keytruda (pembrolizumab) or Opdivo (nivolumab), which restore T-cell activity against cancer cells, or the CTLA-4 inhibitor Yervoy (ipilimumab), which promotes T-cell proliferation.

Tumor-infiltrating lymphocyte therapy is a customized treatment that involves collecting T cells from a patients tumor sample, multiplying them in a laboratory and reinfusing the expanded cells back into the body. TIL therapy is not newit was developed at the National Cancer Institute in the 1980sbut while some patients had very good outcomes, the side effects could be severe, and it took a backseat to checkpoint inhibitor immunotherapy.

The Phase III M14TIL trial compared TIL therapy versus Yervoy in 168 adults with previously treated unresectable (inoperable) Stage IIIC to Stage IV melanoma, nearly 90% of whom had progressed despite treatment with a PD-1 inhibitor. This is the first randomized, controlled trial to compare TIL therapy against a checkpoint inhibitor.

[Checkpoint inhibitors] have a very good safety profile and quite high efficacy and are now often given as first-line therapy, Haanen said. But if patients fail first-line treatments, then the options become very scarce, particularly for patients failing anti-PD-1 drugs, so there is a real unmet need.

The participants were randomly assigned to receive a single round of TIL therapy or up to four doses of Yervoy administered by IV infusion every three weeks. Those assigned to the TIL group were hospitalized and underwent strong chemotherapy to reduce the number of existing lymphocytes and make room for the new ones. After the cell infusion, they received high doses of interleukin-2, a cytokine that stimulates T-cell growth and activity.

People treated with TIL therapy had significantly longer progression-free survival (PFS), meaning they were still alive without disease progression. The median PFS time was 7.2 months with TIL therapy versus 3.1 months with Yervoy, and the PFS rates at six months were 53% versus 21%, respectively. Overall survival also appeared to be longer in the TIL group (25.8 months versus 18.9 months), but follow-up is ongoing. The overall response rate, or tumor shrinkage, was more than twice as high in the TIL group (49% versus 21%), and the complete response rate, or full remission, was nearly three times as high (20% versus 7%).

TIL treatment was generally safe, but side effects were common. Everyone who received TIL therapy and 57% of those treated with Yervoy experienced Grade 3 or higher adverse events. Common side effects included white blood cell and platelet deficiencies, which can lead to infections and excessive bleeding. Most of the adverse events were attributable to the accompanying chemotherapy or interleukin-2 rather than the TILs themselves. However, Haanen noted, these side effects are well manageable and most resolve by the time patients leave the hospital after their TIL therapy.

Speculating about why TIL therapy is effective after PD-1 checkpoint inhibitors have stopped working, Haanen said, We think that the mechanism of resistance to anti-PD-1 treatment is mostly delivered by the tumor microenvironment. So when we take these cells out of their natural environment, reactivate them in the laboratory, grow them up to very large numbers and give them back to the patients, we can overcome some of the escape mechanisms.

Haanen added that TIL therapy has the potential to work against a wide variety of solid tumors, and clinical trials are currently underway for people with many malignancies, including lung, cervical and head and neck cancers.

However, the process is labor-intensive and expensive, which could limit its commercial potential. This study was conducted by academic researchers in the Netherlands and Denmark without pharmaceutical industry involvement. The Netherlands government has agreed to use TIL therapy, and the researchers are seeking approval from the European Medicines Agency. In the United States, the Food and Drug Administration has strict requirements for cell-based therapies, and it may be difficult to win approval without industry support for specific products. That was the path taken by CAR-T therapy, which modifies a patients T cells to make them better cancer fighters rather than relying on naturally occurring immune cells.

Click here to read the study abstract.Click here formore reports from ESMO 2022.Click here to learn more about immunotherapy for cancer.

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Cell-based therapies set to become major players in the osteoarthritis market – Pharmaceutical Technology

Posted: September 25, 2022 at 2:31 am

Osteoarthritis (OA) is a slowly progressive joint disease that is a major cause of disability and pain among the elderly, second only to cardiovascular disease. The OA space is characterised by a high level of unmet clinical need driven by the limited effectiveness of currently available analgesics and the lack of disease-modifying OA drugs (DMOADs). The current standards of care (SOCs) in OA focus on symptom management and are made up of generic pharmaceuticals, including nonsteroidal anti-inflammatory drugs (NSAIDs), opioids, antidepressants, and intra-articular injections. As such, key opinion leaders (KOLs) interviewed by GlobalData strongly believe that the development of DMOADs is the greatest current unmet need in the OA space.

Increased research into OA over the past decade has led to the identification of new targets, and this progress is reflected in the current OA pipeline. Cell-based therapies have the potential to address this unmet need within the OA space to some degree. Within the OA late-stage pipeline, there are two cell-based therapies that GlobalData believes have significant clinical and commercial potential. These are TissueGenes Invossa and Organogenesis Holdings ReNu, both of which have shown disease-modifying efficacy in clinical trials. Invossa has demonstrated the efficacy and safety of a single shot for up to three years, as outlined by Lew in a 2019 study published in Osteoarthritis and Cartilage (NCT03383471). Similarly, ReNu also showed positive efficacy and safety for up to 12 months from a single intra-articular injection (NCT02318511, NCT03063099).

Commercially, these therapies have the potential to be first-in-class DMOADs and to establish a novel paradigm in OA treatment and management. According to GlobalDatas primary research, while GlobalData initially expects a slow uptake for such cell-based therapies due to their high price, as they will require some time to prove their cost-effectiveness, the uptake is likely to improve following the initial lag period as physicians become accustomed to the therapy and as their cost-effectiveness becomes more apparent. Furthermore, the high price associated with these biologics may lead to reimbursement barriers in the genericised OA market, especially in the five major European markets (5EU: France, Germany, Italy, Spain and the UK), where a greater emphasis is placed on drug pricing and cost-effectiveness compared with the US.

However, even with the entry of cell therapies to the market, the unmet need for improved analgesics will likely continue to be largely unfulfilled, and an abundance of opportunities for the development of novel analgesics and additional DMOADs will remain. OA is considered to be a heterogeneous disease with a complicated pathophysiology and unclear aetiology. As such, distinct OA patient populations exist, and therapies targeting these subgroups are needed. Moreover, OA is most prevalent in elderly patients who often have other comorbid conditions, such as diabetes or hypertension, but the currently available treatment modalities for OA are often contraindicated in these patients. Therefore, one of the remaining unmet needs in this disease area is for therapies that address OA and are appropriate to use despite the comorbidities an elderly patient may have.

Overall, considering the novel analgesics and DMOADs in the OA pipeline, GlobalData expects the OA treatment algorithm to change significantly in the future, with cell therapies garnering significant market share during the next decade.

Cell & Gene Therapy coverage on Pharmaceutical Technology is supported by Cytiva.

Editorial content is independently produced and follows thehighest standardsof journalistic integrity. Topic sponsors are not involved in the creation of editorial content.

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Alaunos Therapeutics Highlights Data from TCR-T Library Phase 1/2 Trial at the CRI-ENCI-AACR Sixth International Cancer Immunotherapy Conference -…

Posted: September 25, 2022 at 2:31 am

HOUSTON, Sept. 21, 2022 (GLOBE NEWSWIRE) -- Alaunos Therapeutics, Inc. (Alaunos or the Company) (Nasdaq: TCRT), a clinical-stage oncology-focused cell therapy company, today announced early clinical data from the first patient in its ongoing TCR-T Library Phase 1/2 trial. The data will be presented during a proffered talk at the CRI-ENCI-AACR Sixth International Cancer Immunotherapy Conference (CICON) being held in New York, NY from September 28 through October 1, 2022.

The encouraging data from the first patient in our trial highlight the potential of our non-viral TCR-T cell therapies to treat solid tumors even at the lowest doses in the study design, said Kevin S. Boyle, Sr., Chief Executive Officer of Alaunos. Patients with solid tumors represents a large unmet medical need, and the results from the first patient are quite promising that our TCR-T cell therapy may offer them hope. We look forward to treating additional patients and are grateful for the continued support from our investigators, patients and our dedicated team.

Marcelo V. Negrao, MD, Department of Thoracic/Head & Neck Med Onc, Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center added, These clinical data, where a greater than 51% tumor regression in a patient with NSCLC was observed, are encouraging. We believe this data adds to the growing body of evidence indicating that targeting shared tumor-specific hotspot mutations using TCRs has the potential to transform the way we treat solid tumor cancers. In addition, we believe that the manageable safety and tolerability profile is reassuring, and we look forward to continuing enrollment in the study.

The TCR-T Library Phase 1/2 trial is an open label, dose escalation study being conducted at MD Anderson. The trial is enrolling patients with non-small cell lung, colorectal, endometrial, pancreatic, ovarian, and bile duct cancers that have a matching human leukocyte antigen (HLA) and hotspot mutation pairing in Alaunos TCR-T library.

Key highlights to be presented:

Details of the presentation are as follows:

Title: Objective clinical response by KRAS mutation-specific TCR-T cell therapy in previously treated advanced non-small cell lung cancerPresenter: Marcelo V. Negrao, MD, Department of Thoracic-Head & Neck Medical Oncology, Division of Cancer Medicine at MD AndersonDate and Time: Friday, September 30, 2022, 9:00-9:15am ETSession Title: Session 6: Cellular Therapies: Engineering T cells

The full abstract may be accessed by visiting http://www.cancerimmunotherapyconference.org.

About Alaunos TherapeuticsAlaunos is a clinical-stage oncology-focused cell therapy company, focused on developing T-cell receptor (TCR) therapies based on its proprietary, non-viral Sleeping Beauty gene transfer technology and its TCR library targeting shared tumor-specific hotspot mutations in key oncogenic genes including KRAS, TP53 and EGFR. The Company has a clinical and strategic collaboration with the National Cancer Institute. For more information, please visit http://www.alaunos.com.

Forward-Looking Statements Disclaimer This press release contains forward-looking statements as defined in the Private Securities Litigation Reform Act of 1995, as amended. Forward-looking statements are statements that are not historical facts, and in some cases can be identified by terms such as may, will, could, expects, plans, anticipates, believes or other words or terms of similar meaning. These statements include, but are not limited to, statements regarding the Company's business and strategic plans, the anticipated outcome of preclinical and clinical studies by the Company or its third-party collaborators, the Companys manufacturing capabilities and the timing of the Company's research and development programs, including the expected timeline for enrolling and dosing patients and the timing and forums for announcing data from the Company's clinical trials. Although the management team of Alaunos believes that the expectations reflected in such forward-looking statements are reasonable, investors are cautioned that forward-looking information and statements are subject to various risks and uncertainties, many of which are difficult to predict and generally beyond the control of Alaunos, that could cause actual results and developments to differ materially from those expressed in, or implied or projected by, the forward-looking information and statements. These risks and uncertainties include, among other things, changes in the Companys operating plans that may impact its cash expenditures; the uncertainties inherent in research and development, future clinical data and analysis, including whether any of Alaunos product candidates will advance further in the preclinical research or clinical trial process, including receiving clearance from the U.S. Food and Drug Administration or equivalent foreign regulatory agencies to conduct clinical trials and whether and when, if at all, they will receive final approval from the U.S. Food and Drug Administration or equivalent foreign regulatory agencies and for which indication; the strength and enforceability of Alaunos intellectual property rights; and competition from other pharmaceutical and biotechnology companies as well as risk factors discussed or identified in the public filings with the Securities and Exchange Commission made by Alaunos, including those risks and uncertainties listed in the most recent periodic report filed by Alaunos with the Securities and Exchange Commission. Alaunos is providing this information as of the date of this press release, and Alaunos does not undertake any obligation to update or revise the information contained in this press release whether as a result of new information, future events, or any other reason.

Investor Relations Contact:Alex LoboStern Investor Relationsalex.lobo@sternir.com

1 Cyclophosphamide (60 mg/kg for 2 days) and Fludarabine (25 mg/m2 for 5 days)

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Solving CAR-T’s viral vector problem: Cellares and iVexSol team up to streamline manufacturing – BioPharma-Reporter.com

Posted: September 25, 2022 at 2:31 am

Boasting an outstanding safety record, lentiviral vectors (LVV) are key components in CAR-T cell therapy manufacturing. Unfortunately, owing to the lack of a robust and scalable production platform, therapy providers too often experience highly variable quality, inconsistent yields, and poor recoveries, leading to severe disruptions in the supply chain, said the partners.

By combining Cellares automation and robotics technology with iVexSols viral vector expertise, the two entities aim to develop consistent, high-quality solutions for viral vector manufacturing to improve access to this critical reagent.

iVexSol will supply Cellares with high-quality LVV to support the development of its automated, closed, end-to-end cell therapy manufacturing platform, the Cell Shuttle with an eye on leveraging that technology to automate the entire manufacturing process, including vector production.

While Cellares primary focus has always been cell therapy manufacturing, it said it intentionally developed its Cell Shuttle in a manner that provides flexibility in the processes and technologies that it can support. The platform can be easily adjusted to different customer processing needs and supports a variety of cell therapy modalities.

That company's CEO, Fabian Gerlinghaus, told BioPharma-Reporter: "Both Cellares and iVexSol are focused on creating access to cell therapies. In addition to the actual cell therapy manufacturing bottleneck, we also need to solve the viral vector manufacturing bottleneck. We're working with iVexSol to explore how our automated and flexible bioprocessing technologies can be leveraged to create optimized solutions for viral vector manufacturing. This is a natural fit for our technology since the flexibility to support different bioprocessing workflows has been a central pillar of our architecture from the beginning."

Financial terms of the agreement have not been disclosed.

We spoke to Gerlinghaus back in May where he outlined why automation is key to making cell therapy manufacturing a viable industry.

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Cancer Vaccines Push Toward Viability with New Approaches and Targets – BioSpace

Posted: September 25, 2022 at 2:31 am

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The concept of therapeutic cancer vaccines emerged in the late 1980s but, some 35 years later, it still hasnt resulted in an approved product. The advances in immuno-oncology and adaptive cell therapy that began about a decade ago, however, are enabling fresh, biology-driven approaches with the potential to bring therapeutic cancer vaccines much closer to fruition.

One challenge has been the question of how to elicit an immune response to a tumor, which is a mutated part of the self rather than a foreign entity.

Another problem is that tumors from different sites in the body have different mutations, said Muhammad Al-Hajj, Ph.D., CSO at IO Biotech in an interview with BioSpace. So, while a specific cancer vaccine might work against one tumor, it wont wipe out all the tumor cells throughout the body.

A third hurdle is that tumors protect themselves with a shield of normal cells. For example, Al-Hajj said, In breast cancer, the percentage of actual tumor cells within the mass is less than 50 percent. In pancreatic tumors, 90 percent of the cells are non-cancerous. Thats why pancreatic cancer is so difficult to treat. It brings a whole network of normal cells, that help protect the cancerous cells from the immune system. Therefore, You need something that could wipe out most or all of the cancer cells, he explained.

Boosting the Potential of Immuno-oncology

Checkpoint inhibitors, a leading immuno-oncology strategy, arent effective for all patients. They also have multiple toxicities when combined with other agents.

IO Biotech has a technology platform, called T-win, that activates T cells to directly kill immunosuppressive cells and gently modulate the tumor microenvironment to be less receptive to tumors. Its lead candidate, IO102/IO103, targets the indoleamine 2,3-dioxygenase (IDO) enzyme and programmed death ligand 1 (PD-L1).

Whats particularly novel is that rather than just targeting the cancer cells within the tumor, IO Biotech is developing a vaccine against the key elements within the tumor that pushes the T cells away.

Vaccination modulates the environment in a way that is very gentle and non-toxic, Al-Hajj said. This is not a standard vaccine. Its a vaccine for tumor microenvironment targets. The idea is to modulate the tumor microenvironment and to combine (the vaccine) with a very powerful immune therapylike a checkpoint inhibitorto allow them to infiltrate better.

A Phase I/II trial of 30 melanoma patients showed that vaccination elicited a response in about 80 percent of the patients, whereas a checkpoint inhibitor elicited a response in slightly less than 50 percent.

Biomarker analysis proved the cells start to infiltrate the tumor. Now we are working to prove it in a much larger trial, Al-Hajj shared. Additional clinical trials are underway in first-line solid tumors and as a neo-adjuvant/adjuvant for solid tumors for lung, head & neck and bladder cancers. The vaccine holds FDA breakthrough designation.

There are, of course, many different approaches to therapeutic cancer vaccines.

Targeting the Lymph Nodes

Elicio Therapeutics is targeting the lymph nodes - which the company calls the brain center of the immune system - with its Amphiphile (AMP) platform.

The role the lymph nodes play in organizing the immune response has been known for a very long time, said Pete DeMuth, Ph.D., CSO at Elicio. But, I think we just assumed that after injection, everything sort of went there eventually so it didnt need a lot of intentional design consideration.

Over time, though, scientists discovered there actually were very large differences in the way injected agents distribute throughout the body, DeMuth told BioSpace. Now were starting to see an emphasis on lymph node targeting because we understand enough about the underlying biology to design technologies that allow us to optimize lymph node delivery.

One of the first challenges in this approach is to design molecules of the optimal size to reach the lymph nodes.

Molecules that are too large or too small wont get there very well, DeMuth said. Then, once the molecules arrive, they must be delivered to the right cells within the lymph nodes.

So, Elicio founder and MIT professor Darrell Irvine, Ph.D., designed AMP to direct drugs or other payloads to the lymph nodes. His approach leveraged engineering, material science and biology.

We modify a vaccine molecule by linking a lipid to it to teach the immune system how to collect it and use it as information to develop a response that will protect against cancer, DeMuth explained. The lipid allows the vaccine to bind to albumin (a protein in the tissue), which acts as a shuttle bus to transport things from the tissue into the lymph nodes. The AMP is like the bus pass that allows these agents to get on the shuttle bus.

This system can be applied to many different vaccine or drug agents, including possibly drugs that were limited in their activity because they couldnt reach the immune cells or because they went to other places in the body and caused toxicities, he suggested.

By giving them this AMP modification, (they go) straight into the lymph nodes where they can modulate the biology of the immune cells and simultaneously reduce their exposure to other sites in the body that might drive safety concerns or have toxicities that would limit their usefulness.

The AMP system is currently undergoing a Phase I trial to treat mutant KRAS-driven cancers in the gastrointestinal tract or lungs. Early results havent been released, but DeMuth says he is very optimistic given our preclinical results and the history around this type of therapy.

Going After Cancer Cells Survival Mechanism

In another advance, IMV Inc. recently announced positive data in metastatic bladder cancer patients using its cancer vaccine, Maveropepimut-S (MVP-S) also known as DPX-Survivac.

It shows complete responses, even in patients who had already progressed through immune checkpoint inhibitors. Response are beyond 600 or 700 days and are still ongoing, said Jeremy Graff, Ph.D., CSO, in an interview with BioSpace.

What makes MVP-S unique among cancer vaccines is that its designed to instigate an immune response to a very common cancer protein called survivin, Graff said. Survivin is a protein that many cancers up-regulate during progression. As the name implies, it actually enables the survival of cancer cells.

What distinguishes MVP-S from prior cancer vaccines, Graff explained, is that we not only put the information into our therapeutic to provide a specific survivin signal, but we also put information to instigate the functionality of antigen-presenting cells (APCs) as well as CD4 T cells. This approach encapsulates multiple pieces of instruction that drive an immune response.

The duration of response for survivin-specific T cell activation exceeds two years. Duration is particularly important. CAR T cells often dont persist even though we put billions of cells into patients, Graff noted.

Data released from a Phase IIa study in summer 2021 showed durable responses among ovarian cancer patients that extended progression-free survival to about 20 months in nearly half the patients (who had already been exposed to multiple chemotherapies) who were treated with MVP-S. This was compared to about 10 to 12 months for those treated with chemotherapy.

A new trial has been submitted to the FDA and Health Canada to assess the clinical benefit for MVP-S and low-dose intermittent cyclophosphamide in platinum-resistant ovarian cancer patients.

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ImmunoScape Raises $14M to Facilitate the Discovery and Characterization of Cancer-Specific T-cell Receptors – Business Wire

Posted: September 25, 2022 at 2:31 am

SAN DIEGO & SINGAPORE--(BUSINESS WIRE)--ImmunoScape, a pre-clinical biotechnology company focused on the discovery and development of next-generation TCR-T-cell therapeutics today announced that it has raised $14M in new financing. Existing investor Anzu Partners led the round with participation from new investor Amgen Ventures and Singapore-based global investor EDBI.

ImmunoScapes differentiated Deep Immunomics platform utilizes the companys proprietary combinatorial barcoding technology to enable the discovery and in-depth characterization of rare cancer-specific T-cells at high resolution. ImmunoScapes platform is able to simultaneously evaluate tens of millions of T-cells in blood samples from hundreds of cancer patients to identify rare clinically relevant T-cell clones. The corresponding TCRs are then evaluated and prioritized to build a diverse portfolio of TCR-T-cell therapies.

By leveraging computational biology and machine learning, together with high throughput screening and evaluation of T-cell clones, ImmunoScape is able to efficiently identify novel T-cell therapy targets and TCR candidates. ImmunoScape has extensively validated its computational platform using virus-specific T-cells and is applying the same methods to build an extensive portfolio of cancer-specific TCRs.

We have made significant strides in our discovery program and have identified several compelling clinical TCR candidates using our Deep Immunomics platform, said Choon Peng Ng, CEO, ImmunoScape. The new funding will allow us to expedite our development efforts and help us to advance our therapeutic candidates toward the clinic. We are especially delighted that Amgen Ventures has become an investor and we look forward to working with their team to address important unmet medical needs with ImmunoScapes technology.

Amgen invests in promising new solutions to address healthcares biggest challenges, especially those that offer unique, value-based approaches that align with our mission to serve patients fighting serious illness, said Philip Tagari, vice president of research (therapeutic discovery), Amgen. ImmunoScapes Deep Immunomics and machine learning platforms have the potential to help uncover new treatments as we continue to develop the next generation of innovative medicines. We are excited to work with their team to unlock the full power of this technology.

With research laboratories in both San Diego and Singapore, ImmunoScape is one of the global pioneers of TCR discovery. Their unique high-throughput TCR discovery and evaluation platform has an unprecedented capacity to test millions of human T-cells against hundreds of cancer antigens, said David Michael, managing partner at Anzu Partners. From their origins at Singapores Agency for Science, Technology, and Research (A*Star), the companys global team of immunologists are pursuing major breakthroughs in TCR cell therapy. We are delighted to work more closely with Amgen on these important efforts.

To learn more about ImmunoScape, please visit https://immunoscape.com/.

About ImmunoScapeImmunoScape is a pre-clinical biotechnology company focused on the discovery and development of next-generation TCR cell therapies in the field of oncology. The company's proprietary Deep Immunomics technology and machine learning platforms enable highly sensitive, large-scale mining and immune profiling of T cells in cancer patient samples to identify novel, therapeutically relevant TCRs across multiple types of solid tumors. ImmunoScape has multiple discovery programs ongoing and will be progressing towards IND-enabling studies and entry into the clinic. For more information, please visit https://immunoscape.com/.

About Anzu PartnersAnzu Partners is an investment firm that focuses on industrial and life science technology companies with the potential to transform their industries. Anzu works with entrepreneurs to develop and commercialize technological innovations by providing capital alongside deep expertise in business development, market positioning, intellectual property, global connectivity, and operations. For more information, please visit https://anzupartners.com/.

About Amgen VenturesAmgen Ventures is Amgen's corporate venture capital fund, dedicated to investing in emerging companies and technologies to advance promising new medicines and solutions to healthcares biggest challenges. For more information, please visit https://amgenbd.com

About EDBIInvesting since 1991, EDBI is a Singapore-based global investor in select high growth technology sectors ranging from Information & Communication Technology (ICT), Emerging Technology (ET), Healthcare (HC) and promising Singapore SMEs in strategic industries. As a value creating investor, EDBI assists companies achieve their ambitious goals by leveraging our broad network, resources, and expertise. With our growth capital, EDBI supports companies seeking to expand in Asia and globally through Singapore. For more information, please visit https://www.edbi.com.

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Prescient Therapeutics (ASX:PTX) unveils new treatment to boost CAR-T performance – The Market Herald

Posted: September 25, 2022 at 2:31 am

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Prescient Therapeutics (PTX) has unveiled a novel adjuvant for enhancing cellular immunotherapy.

The CellPryme-A product was designed to be administered to cancer patients as an intravenous infusion in combination with cellular immunotherapy, such as PTXs CAR-T cell therapy. This is used to address the hostile tumour microenvironment that cellular immunotherapies face.

CellPryme-A can be administered either before or alongside cellular immunotherapy.

Prescient said in animal models, CellPryme-A had been shown to reduce the number of suppressive regulatory T cells surrounding solid tumours that counteracted the effectiveness of CAR-T and other cancer therapies.

While CellPrymeA demonstrated superior tumour killing and host survival in pre-clinical studies, its effects were even greater when used together with Prescients CAR-T manufacturing technology, CellPryme-M.

The company presented this new data at the seventh annual CAR-TCR Summit in Boston.

Prescient Managing Director and CEO Steven Yatomi-Clarke said the company was delighted to finally unveil CellPryme-A as a distinct but complementary addition to CellPryme-M.

Together with Prescients next-generation CAR platform, OmniCAR, Prescient has placed itself enviably at the forefront of cellular immunotherapy by creating technologies that overcome the challenges facing the field, Mr Yatomi-Clarke said.

The company said CellPryme-Awas now ready for clinical testing and could be incorporated into clinical studies of existing cell therapies.

Prescient Therapeutics was down 1.35 per cent and trading at 18 cents at 1:29 pm AEST.

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Rationale for Lenvatinib plus Pembrolizumab Therapy in Frontline Setting in Advanced Clear Cell RCC – Targeted Oncology

Posted: September 25, 2022 at 2:31 am

Nizar Tannir, MD: Thank you, Scott, for sharing with us the data from the CLEAR study. I wanted to take this opportunity to ask Moshe [a question]. Moshe, youre familiar with the data, and you saw the data on the slides that Scott presented. In your mind, whats the rationale of combining lenvatinib with pembrolizumab? Is this impressive? The CR [complete response] rate was 16%, OR [overall response] was 71%, median PFS [progression-free survival] was 23.9 months, with a PFS hazard ratio of 0.39 and the OS [overall survival] benefit. Is that because lenvatinib is a potent VEGFR TKI [tyrosine kinase inhibitor]? Or do you think the fact that it also inhibits BFGF plays a role and produces these impressive results? Whats your take on that?

Moshe Ornstein, MD, MA: That was a great overview of the data. In some ways, were working backward. Of all the I/O [immuno-oncology]TKIs that have been approved, the CLEAR trial with lenvatinib and pembrolizumab was the last piece of the puzzle. That said, despite it being the last piece of the puzzle, it sets the bar and the new benchmark for what wed need to see to change the standard of care for treatment-nave metastatic clear cell RCC [renal cell carcinoma].

Getting to your question as to why those results were so impressive, Im not convinced that any single TKI is necessarily better or stronger based on the specific targets. Because theyre all VEGFR inhibitors, more important perhaps than the individual targets is the dosing. For the population at large, theres the concept of linear pharmacokinetics when it comes to VEGFR TKIs, such that collectively, a higher dose is generally equated with a higher plasma level and a better response. That said, there are some patients with very high doses whose cancers dont respond, and some patients on very low doses who have exceptional anti-tumor responses.

The No. 1 reason why the efficacy in this regimen was so impressivewith the I/OTKIs were looking at that up-front benefit of response rates and PFSis because they started at a high dose of lenvatinib at 20 mg and, as well see when we review the other I/OTKI regimens, there were different doses for the TKI. If you were to ask many kidney cancer specialists 3 or 4 years ago what data they would need to see from an I/OTKI regimen to have it set as a new benchmark, with numbers like a response rate of 70%-plus, a PFS of close to 2 years, and complete response rates of 16%, most would have said that numbers like that would at least make this combination extremely competitive in the growing landscape, if not set it apart as the optimal choice for the patient who can tolerate the toxicities and that dose of TKI.

Ill summarize by saying that these data are extremely impressive. They set a new benchmark for efficacy in the response rate, CR rate, and PFS components. I also think its related more to the dosing than it is to lenvatinibs different targets compared with some of the other TKIs.

Transcript edited for clarity.

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