Some ICE detainees in Florida get COVID vaccine in federal court settlement

 Some South Florida detainees in immigration detention have begun to receive the COVID-19 vaccine as part of a Miami federal court case settlement.

U.S. Immigration and Customs Enforcement administered Moderna shots at the Glades County Detention Center in Moore Haven late last week, detainees and immigration lawyers told the Miami Herald. Still to go are detainees at the Krome Processing Center in Miami-Dade and the Broward Transitional Center in Pompano Beach, though it’s unclear when that will take place.

The vaccination rollout at Glades is ICE’s second reported vaccine distribution at a detention facility. The first vaccinations took place in New York after a federal judge slammed the agency for “doing nothing to get [detainees] the vaccine. Nothing. Zero.”

The court settlement — which was filed under seal at the request of ICE — is part of an ongoing civil rights lawsuit that was launched more than a year ago by national immigration advocates. The class action suit, filed at the beginning of the pandemic in April 2020, initially sought the release of thousands of detainees at the three South Florida facilities as COVID-19 ran rampant. In the original 111-page complaint, detainees say their imprisonment violates their due process rights by creating an undue increased risk of severe illness or death.

Though populations inside the detention centers were significantly reduced to allow for social distancing and many were released as a result of a court order, close to 75% of the detainees remained in ICE detention due to previous misdemeanor or felony charges, court records show. A year later, as part of a final settlement, ICE agreed to vaccinate detainees at the three centers.

Despite COVID-19 spreading quickly inside ICE detention facilities, the agency has yet to establish a national vaccination program and cannot say how many detainees have been vaccinated. Unlike the Bureau of Prisons, ICE says it’s relying on state and local health departments to procure vaccine doses.

Details on the entire settlement won’t be made public until both parties get court approval of a proposed injunctive order. Both ICE and immigration advocates are waiting for the court to approve their final settlement within the next week. If not, the case will head to trial on April 27.

According to court records, ICE says the agency has a vaccination plan for the three facilities. ICE officials denied several Herald requests seeking a copy of the plan but instead provided a statement via email.

“At this time, a limited number of ICE detainees have begun to receive the COVID-19 vaccine based on availability and priorities for vaccinating individuals in the state where they are currently detained,” said Miami ICE spokesman Nestor Yglesias.

For Duan Dixon, a Jamaican citizen held at Glades, getting the COVID-19 vaccine was “an answered prayer.”

“Whatever their plan is for us detainees, I’m just glad I was able to get the shot. I have kids that I want to live to see,” said Dixon during a video chat interview with the Herald. Dixon, who has been held in ICE detention for eight months awaiting deportation, said “every additional day in here is a death risk, and at this moment, everybody is fighting for survival — including me.”

But not all detainees see it that way. Dixon, and a handful of other Glades detainees, said the majority of detainees refused the vaccine.

“Most of the inmates, like me, are refusing to be vaccinated,” said Edwin Zeron, a detainee who has since been released. “Like the others, I stated fear for my life. You think I’m going to trust ICE, the same people who imprisoned me, to inject what’s likely to be poison into my body? Hell no. I don’t trust them.“

The strong refusal to get vaccinated has some immigration advocates wondering if ICE has done enough to educate detainees on the public health crisis, including vaccination literacy. Other concerns include ICE approaching the detainees themselves, as opposed to a public health entity or agency.

“While the recent vaccinations at Glades is an important, positive step, we continue to monitor the actions ICE is taking to provide relevant information regarding the vaccine to those in its custody and what steps ICE is taking to encourage people to accept the vaccination,” said Jessica Schnieder, director of the detention program at Americans for Immigrant Justice, one of the six national immigration law firms representing the ICE detainees in the case.

As part of a settlement that’s still in the works, ICE agreed to conduct educational presentations to detainees at the three facilities about the benefits of vaccination in terms of personal and public health.

But that’s not how it panned out, detainees say.

“There weren’t really any presentations, really,” Dixon said. “It was all very quick. ICE came in, said we had the option of getting vaccinated or signing a refusal form and not getting the vaccine. That was done in English and Spanish and then they left. In total, it all probably took like a few minutes.”

Cases of detainees with the coronavirus continue to skyrocket at detention centers nationwide. As of Thursday night, ICE data shows the Glades County Detention Center has had at least 188 reported COVID-19 cases. Krome’s tally is currently at 243 and Broward’s center is at 253.

Though COVID-19 vaccination has begun in prisons and jails across the United States, little is known about vaccination programs in U.S. immigration detention. Experts following the rollout of vaccines at local jails and prisons say targeted vaccination efforts at such facilities are essential, noting that 90 of the 100 largest COVID-19 cluster outbreaks in the United States have taken place at detention centers.

Congressional investigations have revealed that widespread failures in providing healthcare have led to COVID-related deaths of detainees in multiple facilities, including Glades. There is currently no organization tracking vaccination efforts in ICE detention.

https://www.miamiherald.com/news/local/immigration/article250847794.html

Startup sets out to tackle the gene therapy manufacturing crisis

 After Kelli Luginbuhl finished her PhD, her advisor, Duke bioengineer and PhaseBio co-founder Ashutosh Chilkoti, sat her down and asked if she wanted to launch and then run a company. Chilkoti had a once-obscure technology he and the venture capitalist Joe McMahon thought could form the basis of his second company and finally pay huge dividends. Luginbuhl knew the tech from years in his lab and was already looking for biotech jobs. It all added up.

Three years, some strategizing, and 10 or so pitch meetings later, the trio is launching Isolere Bio, with $7 million in seed funding led by Northpond Ventures and technology they believe can allow gene therapy companies to vastly increase the number of doses they can produce. It’s one potential solution to a slow-boiling crisis that has become increasingly acute, as new companies struggle to get the materials they need for trials and some common diseases remain theoretically unfixable by gene therapy, because companies would never be able to make enough doses for that many patients.

The problem is partially that the facilities don’t yet exist to produce this much of gene therapy. Experts, however, also point to antiquated manufacturing processes.

“In gene therapy, manufacturing has a lot of inefficiencies to overcome, which our technology is uniquely positioned to address,” Luginbuhl, who serves as CEO, told Endpoints News.

Large pharma companies and CDMOs have known about the gene therapy manufacturing shortfall for a few years, spending billions to retrofit old drug-making facilities or build new ones to assure capacity for a future where hundreds of gene therapies are in clinical trials and dozens are on the market (currently only two are approved in the US, both for rare diseases). More recently, though, a small handful of startups have tried to not only build new factories but reinvent how gene therapies are made, turning a largely academic process into an industrial one. That includes the George Church spinout 64xBio and the monstrously backed Bob Nelsen startup Resilience.

Like Resilience and 64x, Isolere is trying to boost the production of AAV, the non-disease causing virus that most gene therapy companies use to deliver healthy or functional replacement genes into patients. They’re doing so by changing one obscure process in the manufacturing chain: how AAV is filtered out of the huge bags of cells used to produce the virus.

AAVs are large, 20-sided particles, but currently manufacturers filter the viruses out with the same decades-old proceses they would use for much smaller molecules: chromatography columns, vertical tubes where you mix a solution from the cells with beads that bind to and prevent the AAV from passing through initially, while everything else flushes out. It’s highly inefficient, though, Luginbuhl said. Among other issues, the columns have low capacity. Between 70% and 80% of the solution is generally lost, Luginbuhl said.

Chilkoti’s lab is known for its work on biomaterials, the ones he put to use founding PhaseBio, hoping to build drugs that floated through the body differently and enabled more patient-friendly dosing regimens. The biomaterials Isolere is bringing forward bind to the AAV and form the same kind of liquid-liquid separation as you see in oil in water emulsions — like a protective bubble around AAV, separating it from the rest of the solution.

That material can shepherd the AAV through the filtration process, Luginbuhl said. The goal is to improve yields by 50%.

It’s “a huge pain point in AAV manufacturing that we’re positioned to address,” she said.

Luginbuhl said their technology can work on any AAV and added, relatively seamlessly, into existing manufacturing processes. So far, they’ve only tested it on 2 liter tanks, but she said they’ve been working with major gene therapy companies and hope to sign a co-development deal that would let them scale up the process.

The goal is to get to the market in 16 months. A Series A is in the works, she said, but of lesser concern. For now, they have the runway, she said, and the field is in dire need of new techniques.

“You hear that quote that we’re training children for jobs that don’t exist today,” she said. “The medicines of the future are modalities we may not even know exist today. And so it’s important to be ready to manufacture the next generation of medicines.”

“To do that we need new ideas and new innovations in manufacturing,” she added. “The downstream purification field had really remained quite stagnant.“

https://endpts.com/an-old-academic-and-biotech-founder-re-emerge-to-tackle-the-gene-therapy-manufacturing-crisis/

Gene therapies in the knee? Startup hopes to crack osteoarthritis

 Running preclinical animal studies in mice, rats and rabbits is par for the course in biotech, but horses? Usually too big and too expensive. But it turns out horses have one major advantage for musculoskeletal researchers: As large mammals, their knee joints are big enough to provide a meaningful comparison to human patients.

That’s why a new gene therapy startup out of Palo Alto, CA, dubbed Genascence, used more than 50 of the animals in an early test for its osteoarthritis candidate. Running tests on horses provided the earliest clues on structural improvement and pain reduction — horses don’t limp unless they’re feeling pain, CEO Thomas Chalberg tells me — that Genascence is now hoping to replicate for the first time in humans.

On Wednesday, Genascence uncloaked with early interim safety and tolerability data from that Phase I test of candidate GNSC-001, an AAV-delivered gene therapy containing the coding sequence for the IL-1 receptor antagonist. Developed on the back of science from co-founders Chris Evans, Steven Ghivizzani and Paul Robbins, the therapy looks to tamp down IL-1 signaling, a key driver of inflammation and cartilage destruction in patients with osteoarthritis, the company said.

In the nine-patient, three-cohort dose escalation study, just one patient posted a mild/moderate side effect on the therapy with no signs of neutropenia associated with systemic IL-1 antagonist therapy, the company said. Those results are good enough for Genascence to push its lead drug into a Phase II study, for which it has already filed its IND with the FDA’s backing.

The story of how Genascence came to be started back in 2004, with a pivotal paper from Evans describing the applicability of gene therapy for osteoarthritis in joints. It wasn’t a no-brainer pursuit, Chalberg said, as researchers at the time saw joints as “biology-free” targets

But the idea of a gene therapy for osteoarthritis wasn’t new. In fact, in July 2007, the field nearly came to a screeching halt. After a patient’s death following two doses of a therapy that encapsulated a molecule identical to Enbrel inside an AAV2 capsid, the FDA slammed a clinical hold on the study from a company named Targeted Genetics, according to a review Evans, Ghivizzani and Robbins later penned in Arthritis Research & Therapy.

Even before the death, eight patients in that Phase I study showed severe side effects, casting doubt both on whether the drug was adequately injected in the intra-articular space of the knee and whether a second dose of the therapy spurred a severe immune response. The post hoc results were inconclusive, but importantly the FDA later allowed the trial to resume, adding a big red flag but not killing the field’s chances altogether.

During his time at Pitt, Evans, now the director of the musculoskeletal gene therapy research laboratory at the Mayo Clinic, worked with both Ghivizzani and Robbins and were certainly aware of the setback. All three eventually moved on to other universities but stayed in contact with the idea.

With the goal of succeeding where others had failed, the three first tried their therapy in horses housed at the University of Florida, where Ghivizzani currently works. Chalberg, a Genentech vet and former CEO at Avalanche Biotechnologies before it merged with Annapurna to become Adverum, first heard of the concept in 2016 and was interested in the implications of taking gene therapies out of the field of monogenic rare disease and into broad disease areas, like immunology, where there are still big unmet needs.

“We sort of initiated a conversation at that point before the Phase I trial had started about setting up a company and bringing this project forward,” he said.

Osteoarthritis of the knee is a case in point. The most common therapies for the condition are acetaminophen, NSAIDs and steroids, Chalberg said, and don’t work very well for patients. Many patients progress to needing a knee replacement, which offers more complications later in life. Meanwhile, biologics haven’t provided much help as they rapidly clear out of the knee, and systemic therapy can be tied to serious side effects.

Using a localized gene therapy enclosed in the knee joint, meanwhile, offers the opportunity to use minuscule amounts of the AAV vector used to transport the therapy and prevent any “systemic leakage” into other tissues, Chalberg said. The Phase I data that Genascence will highlight at next week’s American Society of Gene & Cell Therapy meeting shows a manageable safety profile without systemic side effects. The study wasn’t powered to determine efficacy, Chalberg noted, but the Phase II test is expected to be controlled to draw some conclusions there.

Genascence is focusing its efforts primarily on GNSC-001 as it enters Phase II, but Chalberg said the biotech is thinking of ways to expand its pipeline into other osteoarthritis indications and beyond. The immediate next steps seem obvious — going after OA in the hips, hands and spine — but the possibility for other localized immunology therapeutic uses isn’t out of the question for a later focus.

“What we’re really interested in here is addressing the major unmet need,” Chalberg said. “We’ve so learned so much about these (AAV) vectors … over the last 20 years in the gene therapy field, but taking this into an area that’s not monogenic but still a major unmet need, we think there really may be something exciting to pursue.”

https://endpts.com/gene-therapies-in-the-knee-with-the-help-of-a-small-herd-of-horses-a-new-startup-hopes-to-crack-osteoarthritis/

Adagio: 1st peek at Covid-19 antibody data shows preventative numbers may rival mRNA vaccines

 Tillman Gerngross certainly wasn’t the first to tackle Covid-19 antibodies, but he has reason to believe he and his team at Adagio could be the best. Now, we’re getting a first peek at human preventative data for Adagio’s lead antibody, and it looks up to par with the best of the vaccines.

Now, Adagio is churning out early data from that Phase I test showing a single dose of antibody ADG20 offered broadly neutralizing activity in healthy volunteers comparable to peak titers reported from the mRNA vaccines and could offer protection for up to 12 months, the biotech said Wednesday. There were no hard numbers immediately available.

Based on those findings, Adagio has launched its global Phase II/III EVADE study that will test ADG20 in both the pre- and post-exposure settings at 100 sites. The study will evaluate an initial 200 adults in Phase II before potentially opening enrollment to adolescents and pregnant women in Phase III. The primary efficacy endpoint in both cohorts is the prevention of laboratory confirmed, symptomatic Covid-19, Adagio said.

“Based on its potent and broad activity and extended duration of effect in preclinical models, we believe that ADG20 has the potential to provide both rapid protection in the face of a known, recent exposure to an individual with SARS-CoV-2 infection as well as durable protection over several months, including for individuals who are unlikely to have a sufficiently protective immune response to vaccines,” CMO Lynn Connolly said in a statement.

Based on science from Gerngross and his team at Adimab, Adagio has made a late push to bring a better Covid-19 antibody to market after some mixed results from drugmakers who raced other candidates to market and have seen limited efficacy against variants.

In April, Adagio snared $336 million as part of a Series C round led by RA Capital to advance ADG20 through a pivotal Phase I/II/III trial for the treatment of high-risk, mild to moderate Covid-19 patients. That trial, dubbed STAMP, stands apart from the preventative study Adagio read out Thursday.

The company believes its antibodies have broadly neutralizing potential against the SARS-CoV-2 emerging variants as well as other sarbecoviruses apart from the novel coronavirus, Adagio said. That could mean some staying power post-Covid.

STAMP is designed to rapidly turn out proof-of-concept data that could form the basis for an emergency use authorization filing, Adagio said.

https://endpts.com/adagio-offers-first-peek-at-covid-19-antibody-data-with-preventative-numbers-that-may-rival-mrna-vaccines/

Childhood cancer-focused Day One tees up $100M IPO

 After a busy year of fundraising, building its team and picking up new assets, Day One Biopharmaceuticals is heading to Wall Street. The company filed to raise up to $100 million in its IPO, which will bankroll clinical trials of its lead program in multiple cancers and fuel its hunt for more assets to add to its pipeline.

Though Day One is working on cancer treatments for patients of all ages, its starting point is children, who often remain an afterthought in oncology drug development. It will use the IPO proceeds to continue the development of its lead asset, a RAF inhibitor called DAY101, as a treatment for the most common brain tumor diagnosed in treatment, progressive low-grade glioma (pLGG).

That includes a pivotal phase 2 study for children and young adults with relapsed or progressive low-grade glioma, a phase 3 trial testing DAY101 as a potential frontline treatment for this type of brain cancer, and a phase 2 trial in adults with RAS or RAF-altered solid tumors, the company said in a securities filing. The company will list under the ticker “DAWN.”

Day One will also start a phase 1b/2 study of DAY101 in combination with pimasertib, a MEK inhibitor the company picked up from Merck KGaA. The study will test the combo in adults with MAPK-altered solid tumors.

Besides bankrolling clinical trials for DAY101, the IPO haul will help get Day One ready to commercialize the drug. It will also fund the company’s search for more preclinical and clinical programs to acquire or partner on and the development of those programs toward IND filings and the clinic.

Founded in 2018, Day One emerged from stealth in May 2020, with $60 million to develop DAY101, licensed from Sunesis Pharmaceuticals, which previously licensed the asset to Takeda. Five months later, founding CEO Julie Grant handed the reins to Jeremy Bender, Ph.D., who previously oversaw acquisitions, partnerships and investments at Gilead as its vice president of corporate development.

In February, the company raised $130 million in its series B round and licensed pimasertib and a second oral MEK inhibitor from Merck KGaA. The German pharma had taken both drugs through phase 2 in multiple cancers but decided against going further into the clinic.

Day One is the latest in a series of biotech companies that have filed to raise a $100 million IPO in recent months. Others include the asset-centric drug developer, Centessa Pharmaceuticals, cytokine player Werewolf Therapeutics and cancer-focused Rain Therapeutics.

If recent deals are any indication, the $100 million IPO has become a placeholder for much larger sums. Recursion Pharmaceuticals and Bolt Biotherapeutics both filed to raise $100 million in their Wall Street debuts; they ultimately raised $436 million and $230 million, respectively. Sana Biotechnology, which aimed for $150 million in January, wound up raising a whopping $587.5 million.

https://www.fiercebiotech.com/biotech/childhood-cancer-focused-day-one-tees-up-100m-ipo

Lower 'Boiling Point' with agitated bipolar, schizophrenia patients, new campaign advises

 When a situation gets heated, apply some calm. That's what BioXcel Therapeutics' first awareness campaign aims to help healthcare professionals do with agitated bipolar and schizophrenia patients.

The "Boiling Point" campaign focuses on de-escalation techniques, aiming to help providers in emergency medicine and psychiatry identify signs of agitation and defuse the situation before it becomes dangerous to them or the patient. 

The effort centers on the “Partners in Calm” website for professionals treating patients with schizophrenia and bipolar disorder. BioXcel says the key to controlling the situation is to act quickly and calmly.

As a young company specializing in neuroscience and neuropsychiatric conditions, BioXcel's “Boiling Point” campaign marks its first venture into disease awareness and education.

“Many hospitals now are instituting educational programs to allow them to train their staffs to be more cognizant of the symptoms and how to verbally de-escalate,” Will Kane, chief commercial officer at BioXcel, said. "This is a way of putting it together in one spot … so that we can build the dialogue around it."

The campaign coincides with Mental Health Awareness Month and the American Psychiatric Association’s annual meeting.

BioXcel's campaign includes ads in publications such as Emergency Medicine News, Psychiatric Times and American College of Emergency Physicians. The company plans to be involved in medical meetings with its awareness messaging in the second half of 2021.

BioXcel has several neuroscience drugs in the pipeline. Its investigational drug BXCL501 to treat agitation in schizophrenia and bipolar disorders has been submitted to the FDA. There hasn’t been a new branded drug for agitation in nearly a decade, Kane noted.

The same candidate, a selective alpha-2a receptor antagonist in an oral dissolving film, has shown promise in ongoing trials to help control agitation in dementia and delirium as well as in opioid withdrawal.

https://www.fiercepharma.com/marketing/bioxcel-emphasizes-de-escalation-key-when-dealing-rising-agitation-mental-illness

Ahead of potential Ozempic approval in obesity, Novo hits 'full go mode' for launch

 Novo Nordisk has started the year on solid footing, thanks in no small part to its GLP-1 portfolio in Type 2 diabetes. With top earner Ozempic due for a decision in obesity this June, the company is gearing up for a busy second half to the year.

Reaching that untapped market will prove challenging, for sure, but the insulin giant is now in “full go mode” on the promotional front, Novo's Doug Langa, executive vice president for North America, said in an interview.

For the first three months of the year, Novo's total revenues clocked in at 33.8 billion Danish kroner ($5.46 billion), rising 7% at constant exchange rates. Notably, the company’s GLP-1 products, comprised of Ozempic, Rybelsus and Victoza, leapt 13% to 11.3 billion Danish kroner ($1.82 billion). That was welcome news for the company, considering Novo posted a 7% decline in insulin sales.

The company’s existing weight loss med Saxenda reeled in about $250 million for the quarter. Around 100,000 patients are on Saxenda today, Langa said, but that’s nothing compared to the market the company could unlock if diabetes mainstay Ozempic wins a coveted nod in obesity this summer.

There are some 100 million people in the U.S. suffering from obesity and around 650 million worldwide, Langa said. Despite that potential, it’s a largely open field—and a difficult one to break into, he added.

“Stigma and bias, reimbursement, the number of healthcare professionals that are actually prescribing and then, importantly, having patients seek treatment—those are all big hurdles to get over,” Langa said. The company views those obstacles as “market development opportunities," he added.

Part of the effort hinges on obesity simply winning recognition as a disease that requires treatment—something Novo’s been working to accomplish for more than 10 years, Langa said. “It’s the only disease that when spoken about, people look away. It’s a disease people whisper about.”

While there are already a few obesity treatments on the market, Ozempic holds a clear advantage, Langa figures. Treating the disease “does take an element of diet and exercise, but there’s also a pharmacological component to it that we know works and we see that in the clinical trial results.”

In data from a phase 3 trial unveiled in February, Novo showed that Ozempic helped one-third of patients lose more than 20% of their body weight over the course of a 68-week study. The average subject lost more than 33 pounds, and many saw improvements in risk factors for diabetes and heart disease. Saxenda, by comparison, helps patients lose around 5% of their body weight on average.

As a potential approval looms, Novo has “been laying the groundwork” for its launch, Langa said. That includes education efforts, key opinion leader development and market access. The company is in “full go mode” when it comes to prepping its sales teams, and it has already started working with payers where it can, Langa said. Meanwhile, he says the company will leverage a mix of digital and in-person outreach as it continues to navigate the pandemic.

One unexpected boost from the pandemic? “This association with COVID-19 and having an increased risk if you had obesity or diabetes or other serious chronic illnesses—I think that that brought an awareness to not only diabetes and the seriousness of it, but also obesity in particular,” Langa said.

Ozempic generated around 6.66 billion Danish kroner ($1.07 billion) for the period. All told, the drug reeled in 21.21 billion Danish kroner ($3.42 billion) in 2020.

After a strong first quarter, Novo is forecasting sales growth this year of 6% to 10% in local currencies, up from its previous estimate of 5% to 9%.

https://www.fiercepharma.com/pharma/novo-after-strong-first-quarter-full-go-mode-for-ozempic-obesity-launch-exec-says