Biotech week ahead, Oct. 11

 Biotech stocks retreated in the week ending Oct. 8, extending losses for the third straight week. Some of the selling in the space was due to money moving out of defensive stocks and into risky bets amid the broader market strength.

Vaccine stocks continued to experience selling pressure in the week. Data readouts and presentations at conferences also moved stocks in either direction.

Xenon Pharmaceuticals Inc. 

XENE +3.73%

 (Get Free Alerts for XENE) was among the biggest gainers after it reported positive topline results from the Phase 2b study of XEN1101 in adult patients with focal epilepsy. On the other hand, Prelude Therapeutics Incorporated 

PRLD +8.48%

 (Get Free Alerts for PRLD) lost about one-half of its market-cap following its presentations at the AACR-NCI-EORTC conference.

Meanwhile, Allogene Therapeutics, Inc. 

ALLO +46.14%

 lost over 100% after the Food and Drug Administration imposed a clinical hold on its CAR T-cell therapy studies following reporting of a chromosomal abnormality in a treated patient.

ChemoCentryx, Inc. 

CCXI +95.97%

 shares benefitted from a positive FDA decision for its avacopan as a treatment for ANCA-associated vasculitis.

Three healthcare companies debuted on Wall Street, raising a combined $452 million.

Here are the key catalysts for the unfolding week:

Conferences

Trends In Medical Mycology Conference: Oct. 8-11 (Aberdeen, U.K.)

American Society of Retina Specialists, or ASRS, 2021 Annual Meeting: Oct. 8-12 (San Antonio, Texas)

Cell & Gene Meeting On The Mesa (hybrid conference): Oct. 12-15 (in Carlsbad, California)

Alliance Global Partners Biotech & Specialty Pharma Conference (virtual conference): Oct. 13

37th Congress of the European Committee for Treatment and Research In Multiple Sclerosis, or ECTRIMS (virtual meeting): Oct. 13-15

European Society for Medical Oncology, or ESMO, Virtual Plenary (virtual meeting): Oct. 14-15

PDUFA Dates

The FDA is scheduled to announce its decision on Avadel Pharmaceuticals plc 

AVDL +1.83%

's new drug application for FT218, an investigational, once-nightly formulation of sodium oxybate for the treatment of excessive daytime sleepiness and cataplexy in adults with narcolepsy. The decision is due by Friday, Oct. 15.

Clinical Readouts/Presentations

ASRS 2021 Annual Meeting Presentations

4D Molecular Therapeutics, Inc. 

FDMT +6.49%

: Phase 1/2 data of intravitreal 4D-125 AAV gene therapy in patients with advanced XLRP. (Sunday, Oct. 10, at 3:56 pm)

REGENXBIO Inc. 

RGNX +2.52%

: 

CLSD +2.41%

: results from the end-of-study Phase 1/2a study of subretinal delivery of RGX-314 for neovascular age-related macular degeneration (Monday, Oct. 11, at 9:38 am-9:44 am)

Regenxbio & Clearside Biomedical, Inc. 

CLSD +2.41%

: Phase 2 data for RGX-314 in wet AMD using suprachoroidal delivery (Monday, Oct. 11, at 9:44 am – 9:50 am)

Aerie Pharmaceuticals, Inc. 

AERI +4.92%

: Topline results from the AR-1105 (dexamethasone intravitreal implant) Phase 2 clinical trial in patients with macular edema due to retinal vein occlusion (Tuesday, Oct. 12, at 11:22 am)

Outlook Therapeutics, Inc. 

OTLK +0.9%

: data from supplemental safety study for ONS-5010/Lytenava, an investigational ophthalmic formulation of bevacizumab for use in retinal indications (Tuesday, Oct. 12, At 12:08 am to 12:14 am)

ECTRIMS Conference Presentations

Atara Biotherapeutics, Inc. 

ATRA +3.23%

: updated open-label extension clinical data and new magnetization transfer ratio imaging data from a Phase 1 study of ATA188 for progressive multiple sclerosis (Wednesday, Oct. 13, at 10:45 am)

ESMO Presentations

Eli Lilly and Company 

LLY +0.3%

: new data from the monarchE study for an investigational use of Verzenio, in combination with endocrine therapy, in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative high risk early breast cancer (Thursday, Oct. 14, at 1:30 pm)

Standalone Presentations

CRISPR Therapeutics AG 

CRSP +4.23%

 will host a virtual event on Tuesday, Oct. 12, at 4:30 p.m. to highlight clinical data from its ongoing Phase 1 study of CTX110 for the treatment of relapsed or refractory B-cell malignancies.

Earnings

Enzo Biochem, Inc. 

ENZ +2.84%

 (Tuesday, Oct. 12, before the market open)
Theratechnologies Inc. 

THTX +0.83%

 (Wednesday, Oct. 13, before the market open)

IPOs

IPO Pricing

Cingulate Inc NASDAQCING, a clinical stage biopharma using its proprietary "Precision Timed Release" drug delivery platform technology, has filed for offering 4.55 million shares in an IPO at an estimated price range of $10-$12. The Kansas-based company has applied for listing its shares on the Nasdaq under the ticker symbol "CING."

Medical device maker PAVmed Inc. 

PAVM +5.61%

's spin-off unit Lucid Diagnostics Inc.NASDAQLUCD has filed a preliminary prospectus with the SEC to offer 5 million shares in an IPO to be priced in the range of $14-$16. The New York-based company has applied for listing its shares on the Nasdaq under the ticker symbol "LUCD."

Lucid is a commercial-stage medical diagnostics technology company focused on treating patients with gastroesophageal reflux disease, also known as chronic heartburn, acid reflux or simply reflux, who are at risk of developing esophageal precancer and cancer, specifically highly lethal esophageal adenocarcinoma.
PAVmed currently owns approximately 72.6% of Lucid's outstanding common stock, and is its controlling stockholder.

Newport Beach, California-based Aeon Biopharma, Inc. NASDAQAEON has filed to offer 5 million shares in an IPO, with the price estimated to be between $14 and $16 apiece.

Aeon is a clinical stage biopharma focused on developing its proprietary botulinum toxin complex, ABP-450 injection, or ABP-450, for debilitating medical conditions, with an initial focus on the neurology and gastroenterology markets. The company has applied for listing its shares on the Nasdaq under the ticker symbol "AEON."

IPO Quiet Period Expiry

DICE Therapeutics, Inc. 

DICE +4.02%

Pasithea Therapeutics Corp. 

KTTA +1.5%

Tyra Biosciences, Inc. 

TYRA +7.68%

https://www.benzinga.com/general/biotech/21/10/23311516/the-week-ahead-in-biotech-oct-10-16-avadel-fda-decision-conference-presentations-and-ipos-take-ce

Predicting COVID-19 Severity in Kids

 Children with severe SARS-CoV-2 infection had significantly elevated levels of a trio of saliva cytokines, according to a preliminary analysis.

In the pilot study with 180 children, those with severe COVID-19 had elevated levels of CXCL10, MIG, and TNF R-1 in their saliva versus children with mild COVID-19, reported Usha Sethuraman, MD, of Central Michigan University in Mount Pleasant, at the American Academy of Pediatrics (AAP) virtual meeting.

While specific cytokine profiles could not be related to various symptoms of COVID-19 infection -- partly due to small sample size -- the researchers hope additional data will enable them to differentiate the biomarkers of pediatric COVID-19 patients, she noted.

"A lot of these children who have COVID have very similar symptoms to those with other common viral infections," Sethuraman told MedPage Today. "And there is no way for us to tell which child is going to get sicker or not. So if we have a method to determine which child is going to develop [multisystem inflammatory syndrome (MIS-C)] or severe COVID, that would help us start treatment earlier."

"So in that sense, this would be a game changer," she added.

COVID-19 cases in children are generally mild, but some younger patients can present with MIS-C, Kawasaki disease, or respiratory failure. In the 24 states and New York City that report on child hospitalizations, children are hospitalized in 0.1%-1.9% of all pediatric COVID-19 cases, according to September 2021 AAP data.

Currently, there are no established biomarkers that can predict the progression and severity of COVID-19 in children, although studies have linked disease severity with enhanced cytokine levels in adults.

Sethuraman said her group chose saliva cytokines because of the ease of sampling. "The primary purpose of this study was to make it as noninvasive as possible," she said.

The study started in March 2021 and will go until June 2022. Initial data from March until May came from the Children's Hospital of Michigan in Detroit and UPMC Children's Hospital of Pittsburgh. The analysis of saliva samples is being done at the Penn State College of Medicine in Hershey, Pennsylvania, while model development using artificial intelligence (AI) is being done at Wayne State University in Detroit.

Of the 180 children (mean age 7.1 years; 49.9% female) enrolled in the study thus far, 60 were hospitalized and 40 were categorized as having severe COVID-19. Of those 40, five exhibited cardiac symptoms, 26 had severe respiratory symptoms, while the others exhibited neither, but "were mostly diagnosed with MIS-C," according to Sethuraman.

Six salivary cytokines -- TNF R-1, IL-13, IL-15, CCL7, CXCL10, and MIG (CXCL9) -- were measured, and all three of the elevated cytokines in patients with severe disease were pro-inflammatory, the researchers reported.

They also found that cytokines did not vary significantly (P>0.05) between various COVID-19 phenotypes, and that a hierarchical logistic regression showed that a three-cytokine-based model accounted for "only 4.2% of the variance between severe and non-severe COVID groups."

"The combined model of the three cytokines with age, gender and asthma status showed moderate accuracy (75%) and poor sensitivity (21%)," the researchers stated, and that was a study limitation, along with the small number of patients.

Sethuraman and colleagues also measured miRNA levels in 129 saliva samples. They found that levels of 63 miRNAs differed significantly between severe and nonsevere cases in their initial analysis, and showed promise as a predictive model.

"Our ultimate goal is to incorporate all features, including social determinants of health and clinical information, and use AI to make a model," Sethuraman said. "[We want] to narrow down to a few miRNA and some cytokines, and develop a bedside tool [that] spits out a prediction for us for whether a child has severe disease."

Disclosures

The study was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development/NIH Rapid Acceleration of Diagnostics (RADx) Program.

Sethuraman disclosed no relationships with industry. Co-authors disclosed relationships with Quadrant Biosciences, Moderna, and Novavax.

Primary Source

American Academy of Pediatrics

Source Reference: Sethuraman U, et al "Salivary cytokines in children with and without severe disease due to SARS-COV-2 infection" AAP 2021.

https://www.medpagetoday.com/meetingcoverage/aap/94942

NYC orders educators to find thousands of students ‘missing’ from schools

 Where are they?

City educators are scrambling to find what some officials fear are 150,000 or more kids who have not yet set foot in school — and others who don’t show up on a given day.

“Reach out to every absent student every day,” the Department of Education instructed principals last week in a memo obtained by The Post.

Schools were told to follow up daily with each missing kid until they nail down the reason why he or she has not shown up — whether for one day or not at all.

“Outreach to families may include phone calls, text messages, postcards, and where possible, home visits,” the memo says.

In another urgent missive, principals told staffers that all schools with more than 20 percent of students absent will get weekly visits from DOE higher-ups — a dreaded occurrence. “We cannot continue in this direction,” one administrator warned.

LaShawn Robinson, the DOE’s deputy chancellor for School Climate and Wellness, could not give an official number of students attending city schools.

William Miller

“No one wants a visit from central when we’re understaffed and missing most of our paras (classroom aides who serve kids with special needs],” a teacher said, referring to a personnel crunch since the vaccine mandate took effect Oct. 4.

“I think they’re getting a lot of pressure to make things look normal when we aren’t being given the tools and staffing we need to be normal for the students.”

The directives went out a day after the City Council’s education committee held an oversight hearing to get answers on COVID-19 testing in schools, quarantines and student attendance.

Brooklyn Councilman Mark Treyger, the education committee chairman, said he had heard from contacts that some 150,000 students “have not come into a building” since classes started Sept. 13.

Councilman Mark Treyger said contacts have told him 150,000 students “have not come into a building” since classes started.

Stephen Yang

“Does that sound right?” Treyger asked LaShawn Robinson, the DOE’s deputy chancellor for School Climate and Wellness.

Robinson called that figure “unofficially, far from accurate,” but she did not give a better number. “We’re focused on every student, every day.” she said. Treyger, who has urged the DOE to offer families a remote instruction option, also hit a brick wall when asking First Deputy Chancellor Donald Conyers how many students are attending city schools.

“I don’t have that number to give you,” replied Conyers, the DOE’s second-in-command to Chancellor Meisha Ross Porter, who did not testify. 

In the same hearing, Michael Mulgrew, president of the United Federation of Teachers, said he believes as many as 180,000 city kids may not have come to school at all, and called for greater efforts to reach them.

Michael Mulgrew accused the DOE of hiding the real attendance numbers from the public.

Kevin C. Downs for The New York Post

Blasting the DOE’s lack of transparency, he charged, “They have an attendance figure for every day. They know how many kids didn’t show up. They are hiding this.”

Anxiety over COVID-19 is at least partly to blame for students skipping school, a Brooklyn teacher told The Post. “Parents keep kids home a lot on unofficial quarantine like when cousins are exposed at other schools. They don’t care about the DOE’s quarantine rules.”

After the hearing, the DOE again refused to disclose the raw number of students currently enrolled in its 1,600 schools.

The city reported a total 955,490 children in Pre-K through high school in the fall of 2020. That was down from 1,002,201 the year before, a loss of 46,711 students,  according to the  Independent Budget Office.

But enrollment may have slipped further during the turbulent 2020-21 school year, when two-thirds of students were instructed remotely and in-person attendance was low.

Officials should give the facts they know instead of “vague and offhand dismissals of public concern,” said David Bloomfield, a Brooklyn College and CUNY Grad Center education professor. 

“The DOE’s refusal to provide accurate enrollment and attendance figures is not only frustrating, but adds to public distrust.”

DOE spokesman Nathaniel Styer promised the agency will cough up some answers soon. 

“We’ll be providing preliminary enrollment data after rolls close at the end of the month,” he said Friday. “We’ve never done that before, but we are committing to getting it done.”

Officials said DOE rosters at the start of every school year include students who have moved or enrolled in different schools — which must be confirmed before they are discharged. 

https://nypost.com/2021/10/09/city-orders-educators-to-find-the-thousands-of-students-missing-from-schools/