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Tuesday, July 28, 2020

AbbVie’s upadacitinib successful in third late-stage dermatitis study

AbbVie (NYSE:ABBV) announces another successful Phase 3 clinical trial, AD Up, evaluating Rinvoq (upadacitinib) plus topical corticosteroids (TCS) in adults and adolescents with moderate-to-severe atopic dermatitis.
The trial met the co-primary endpoints and all secondary endpoints. Specifically, 77% of patients receiving 30 mg of upadacitinib plus TCS achieved EASI 75 (75% improvement in EASI score) compared to 26% in the placebo arm. 59% of patients in the cohort achieved clear or almost clear skin compared to 11% in the control arm. 64% experienced at least a four-grade improvement in itchy skin compared to 15% in the control arm.
Complete results will be submitted for presentation at a future medical conference and publication.
Two previous Phase 3s, MEASURE Up 1 & MEASURE Up 2, were also successful.
The FDA approved the JAK inhibitor for rheumatoid arthritis about a year ago.

NYU launches study of Reata’s bardoxolone in COVID-19

Researchers at the NYU Grossman School of Medicine have initiated a Phase 2 clinical trial, BARCONA, evaluating Reata Pharmaceuticals’ (RETA -0.4%) bardoxolone methyl in COVID-19 patients. The primary endpoint is safety.
Bardoxolone methyl is an oral once-daily antioxidant inflammation modulator that targets the Nrf2 pathway, a regulator of antioxidant proteins that protect against oxidative damage associated with injury or inflammation.

Karuna Therapeutics inks new drug discovery deal

Karuna Therapeutics (KRTX +0.5%) has agreed to partner with privately held PGI Drug Discovery LLC (PsychoGenics) to identify novel candidates for severe neuropsychiatric disorders.
Under the terms of the deal, Karuna will pay PsychoGenics an undisclosed upfront amount for access to its proprietary screening platforms that leverage computer vision and machine learning. Each party is eligible for milestone payments and royalties on net sales.

Corcept launches 2nd late-stage study of relacorilant in cortisol disorder July 28, 2020

Enrollment is underway in a Phase 3 clinical trial, GRADIENT, evaluating Corcept Therapeutics’ (NASDAQ:CORT) relacorilant in patients with Cushing’s syndrome (excessive levels of cortisol in the blood) caused by adrenal adenomas (adrenal gland tumors) or hyperplasia (enlarged glands), a type of Cushing’s representing ~15% of total cases.
The primary endpoints of the 130-subject study are safety, the change from baseline in 24-hour ambulatory blood pressure at week 22 versus placebo and, in participants with diabetes or impaired glucose tolerance, the mean change in area-under-the-curve (AUC) glucose at week 22 versus placebo.
The estimated completion date is June 2021.
Another Phase 3, GRACE, assessing relacorilant in 130 patients with all etiologies of Cushing’s syndrome is ongoing.
The company says the value proposition of relacorilant, a cortisol modulator, is equivalent efficacy to Korlym (mifepristone) without the unwanted side effects such as endometrial thickening, vaginal bleeding and hypokalemia (low blood potassium).

Monday, July 27, 2020

Curevac muddies the Moderna/Arbutus waters further

It took Arbutus and Moderna almost 24 hours to comment publicly on the relevance of Thursday’s legal bust-up, which saw the former prevail in a patent ruling that could threaten the latter’s Covid-19 vaccine. Neither company looks to have covered itself in glory. The entry of Curevac into the fray complicates things further still.
Arbutus admitted that it had actually signed away much of the relevant rights two years ago, and its stock lost 20%. Moderna, meanwhile, claimed that its tech was in fact “not covered by the Arbutus patents”. In that case why did it initiate the legal action against Arbutus to begin with? And is Curevac in the clear?
The German group revealed its hand in a filing with the US SEC for a proposed $100m flotation. In the document Curevac spelled out its reliance on a lipid nanoparticle (LNP) technology developed by Acuitas, a private Canadian company with links to Alnylam, by way of a 2016 tie-up for which it pays an annual $1.1m maintenance fee.
Acuitas is at the centre of the dispute between Moderna and Arbutus, and is also the source of LNPs used by Biontech/Pfizer. The remarkable upshot of all this is that three of the major mRNA Covid-19 vaccine competitors might all in some way rely on the LNP technology in question.
Longstanding aggression
Moderna says it had challenged three relevant Arbutus patents “in response to the longstanding aggressive posture taken by Arbutus”. It also claims that its own LNP technology has advanced beyond what the Arbutus patents describe, perhaps implying that it has largely re-engineered its mRNA approach over the past two years.
Arbutus’s statement, meanwhile, should not have come as a surprise to any investors who had been paying close attention. For the sake of clarity, Arbutus might have won the legal decision, but it spells out that it has at most a 40% interest in the patent in question, US no 8,058,069.
This is because in 2018 it spun rights to the LNP technology that did not relate to hepatitis B into Genevant, a venture with Vivek Ramaswamy’s holding company, Roivant Sciences (The Covid-19 vaccine battle just got interesting, July 24, 2020). Back then no one was thinking about Covid-19, and Arbutus’s key focus was hepatitis B; the venture is 60%-owned by Roivant.
And, for Arbutus investors, it gets worse: Genevant subsequently issued convertible debt, and if this is paid off in new equity Arbutus’s shareholders “will be significantly diluted”. Arbutus says it is, however, entitled to a low single-digit royalty on sales of products derived from the ’069 patent now held by Genevant.
So, with Moderna stock down on Friday, and Arbutus coming off its Thursday blip, who could win here? Clearly Genevant’s majority owner, Mr Ramaswamy, now looks to have had remarkable foresight.
Curevac has so far not been implicated in legal action, so it must be assumed that any rights Acuitas granted it to the ‘069 patent stand. And the same goes for Biontech/Pfizer, which in 2018 struck a licensing deal with Genevant that today looks like the key to the puzzle.
Crucially, Biontech/Pfizer’s BNT162b1 and Moderna’s mRNA-1273 are fierce rivals, so in purely business terms it is in the interests of one to stop the other. But this is Covid-19, a global emergency, where the optics of a move that threatens to delay the availability of a vaccine would be disastrous.
A plain royalty looks to be the simplest answer. If Arbutus investors today look to have lost out, the real winners will emerge later.

Agonizing over school-reopening plans? Think Marie Kondo

Her advice has helped millions declutter their lives. Now organizing expert Marie Kondo’s philosophy of letting go of nonessentials can help K-12 educators scrambling to design creative back-to-school plans in the age of COVID-19, Harvard experts say.
“Imagining September,” a recent report released by researchers from Harvard’s Graduate School of Education (HGSE) and the Massachusetts Institute of Technology, suggests that schools grappling with online and in-person teaching options can keep students more engaged by limiting coursework to the essentials only. Avoid piling on missed material in a “drill and kill” approach, the report suggests, and instead emphasize developing foundational skills and knowledge, while preserving some “in-” time for the arts and extracurriculars.
“The key idea is to just focus on the essential knowledge and skills that kids need to learn in a given year, and then let go of some of the rest,” said Jal Mehta, HGSE professor and co-author of the paper, who helped developed the Kondo idea with Shanna Peeples, the 2015 National Teacher of the Year and a recent graduate from of HGSE’s Doctor of Education Leadership program. “Focusing on essentials allows opportunities for teachers to go deeper, create space to form relationships, build communities, support social emotional learning, extracurriculars, and all the other things that are going to be critical in this upcoming year.”
Peeples said a former mentor helped her come up with the idea of keeping things simple to avoid feeling overwhelmed when planning her own lessons as a teacher. “She advised me to think about what would count as a ‘need to have’ and let go of what’s ‘nice to have,”’ Peeples said. “The pandemic brought that rule of thumb back to me. As educators, it is so easy to put more into our already overfull proverbial closets—that’s the that encourages us to see everything as a potential learning resource. This is even more true of our curricula, overstuffed as it is with all of its ‘nice to haves.’ Everything in our curriculum has a purpose but not everything in our curriculum needs to stay.”
But “Kondo-ing” school priorities is just one of many suggestions contained in the report and accompanying guide for educators developed with input from teachers, administrators, local officials, students, and parents from school districts across the country. “Imagining September” outlines a range of possibilities—everything from a “call a teacher” button that allows students studying online to virtually raise their hands and ask for help from a teacher on call, to substituting typical coursework for seniors in good academic standing with 1,000 hours of volunteering, to encouraging students thriving in virtual classroom settings to keep studying from home while giving students who have limited internet access at home, or those who are most vulnerable, priority for in-school learning time. The report also suggests parents create “microschools” with three to five other families and take turns providing support and supervision for the small groups of learners studying online, and it recommends making students—high achievers as well as those in need of help—a key part of the planning process.
“When people hold these kinds of design meetings with students they often include the editor of the school newspaper, the body council president, or the head of the debate team. School is already working well for those kids,” said Mehta, who took part in three separate planning sessions with students and adults while working on the report. “The person you need at the meetings is the student who was absent 30 times this last year. That’s the kid for whom school is not working.”
Building bonds between teachers and students will be more important than ever, the authors write, as many schools will opt to continue online-only instruction. One way to create those connections, they suggest, is through advisory programs that pair a with a small group of students for virtual weekly check-in sessions.
The researchers acknowledge that every school is different and that there is no “one size fits all,” reopening plan. They hope their work will be a jumping-off point for people to think creatively about the different forms school might take. “We were really not trying to produce a down-the-middle, policy-in-the-box report. Instead we wanted to listen to students and teachers and imagine what could be possible,” said Mehta.
Mehta also hopes the research can help shine some light on what he calls the “dark turn” the national conversation has taken around school reopening since their report was released earlier this month. In recent weeks President Trump and Education Secretary Betsy DeVos have been pushing schools to reopen for in-person instruction despite the surging coronavirus infection rates in parts of the country. Many teachers and unions have balked at the idea of returning to classrooms, with some educators threatening to strike if they are forced back to school.
“What we are urging in this report is that there are lots of options; there are lots of possibilities,” said Mehta. “Some parents want their kids to stay home; some teachers need to stay home. Other parents really badly want their kids to go to school, and we need to work with various stakeholders in an inclusive way and think creatively about how to realize these varied goals.”

Explore further

More information: Justin Reich et al. Imagining September: Principles and Design Elements for Ambitious Schools During COVID-19, (2020). DOI: 10.35542/osf.io/gqa2w

Quarter Of NYC Area Residents Have Had Coronavirus – CDC

Almost a quarter of New York City, Long Island and Westchester residents who had blood surveyed by the Centers for Disease Control and Prevention were found to have had the coronavirus.
That equates to a little more than 2.8 million people. Official city figures had estimated just over 219,000 cases as of July 23.
The CDC partnered with commercial testing labs to estimate infection levels for five states and a handful of large cities. It tested the blood of people who had come to doctors for routine screenings or sick visits, not just those whose care was related to the coronavirus.
Around 23 percent of residents in the New York City area who had blood drawn in late May had antibodies for the virus, according to the CDC. The collection area included Nassau, Suffolk and Westchester counties alongside the NYC boroughs.
The survey was the second of its kind from the CDC. The first, which ended May 3, found a city infection rate of 6.9 percent.
The second survey was conducted between May 21 and 26. A total of 1,116 samples were collected.
The figure was much higher than anywhere else in the nation. Of areas that had a second survey, Washington State had a 2.1 percent infection rate, Utah had 1.1 percent, Minnesota 2.2 percent, Missouri 2.8 percent, Philadelphia 3.6 percent and Connecticut 5.2 percent.
The CDC notes the survey comes with some caveats. It isn’t random and relies on people whose blood was taken for routine screening or sick visits, which may not reflect the population as a whole.
The results reported by the CDC are adjusted for false positive and false negative results. The CDC notes that it is possible that antibody levels may decrease over time and that people who previously tested positive for the presence of antibodies may at some point test negative.
The CDC also warns that the survey shouldn’t be interpreted to mean people who tested positive for antibodies are immune to the virus. It is still unknown how long antibodies last and what level of protection they offer.