Biotech week ahead, March 22

 Biotech stocks reversed course in the week ended March 19 amid mixed news flow on data readouts and lackluster broader market performance.

Rubius Therapeutics, Inc. RUBY 4.33% was among the biggest gainers of the week after the biopharma reported positive Phase 1/2 data for its RTX-240 in solid tumors.

Marker Therapeutics, Inc. MRKR 34.44% had a volatile ride amid an announcement concerning common stock offering and insider buying.

The Muscular Dystrophy Association and the Society of Gynecologic Oncology meetings scheduled for the week provided platforms for multiple presentations by companies. Some of the presentations moved stocks in a big way.

The week also witnessed listings by four biopharma companies, which raised a cumulative $678.84 million in gross proceeds through initial public offerings.

Here are the key catalysts for the unfolding week:

Conferences

The Endocrine Society's ENDO 2021: March 20-23

PDUFA Dates

The Food and Drug Administration is likely to rule on Pacira Biosciences Inc's PCRX 0.79% supplemental new drug application for Exparel as a single-dose postsurgical pain relief treatment for children, aged six and over. The drug has already received clearance from the Food and Drug Administration for the same indication in adults.

Zealand Pharma A/S ADR ZEAL 2.64% awaits an FDA nod for its new drug application for dasiglucagon as a rescue medication for low blood sugar levels in diabetic patients. The PDUFA date is scheduled for Saturday.

The FDA will also announce by Saturday its decision on the BLA submitted by bluebird bio Inc BLUE 4.26% and Bristol-Myers Squibb Co BMY 0.74% for idecabtagene vicleucel, or ide-cel/bb2121, in multiple myeloma. Ide-cel is being developed as part of a co-development and profit-sharing agreement between Bristol Myers Squibb and bluebird bio.

Adcom Meetings

An osteoarthritis drug from Pfizer Inc. PFE 0.7% will be up for discussion at joint meeting of the FDA's Arthritis Advisory and Drug Safety and Risk Management Advisory committees, March 24-25. This is over a biologic license application for a tanezumab injection aimed at relieving osteoarthritis pain in adults. Tanezumab is being jointly developed by Pfizer and Eli Lilly and Company LLY 0.2%.

Clinical Readouts

BioCryst Pharmaceuticals, Inc. BCRX 4.33% will present new Phase 1 clinical trial data on BCX9930, a drug for PNH patients. PNH — paroxysmal nocturnal hemoglobinuria — is a rare blood disorder that causes red blood cells to break apart. The presentation will take place on Monday during the company's virtual R&D meeting.

ProQR Therapeutics N.V. PRQR 2.36% is due to present on Wednesday results from its Phase 1/2 Stellar trial of QR-421a in adults with Usher syndrome and non-syndromic retinitis pigmentosa. Usher syndrome is a rare genetic disorder that affects both hearing and vision.

Earnings

Monday

VolitionRx Limited VNRX 5.64% (after the market close)
BioLife Solutions, Inc. BLFS 4% (after the market close)

Tuesday

aTyr Pharma, Inc. LIFE 6.65% (after the market close)
Bionano Genomics, Inc. BNGO 5.12% (after the market close)

Wednesday

Forte Biosciences, Inc. FBRX 6.08% (before the market open)
Aptinyx Inc. APTX 1.29% (after the close)
TELA Bio, Inc. TELA 2.88% (after the close)
Navidea Biopharmaceuticals, Inc. NAVB 2.64% (after the close)
STRATA Skin Sciences, Inc. SSKN 3.39% (after the close)

Thursday

Vascular Biogenics Ltd. VBLT 1.48% (before the market open)
Genetron Holdings Limited GTH 0.35% (before the market open)
Synlogic, Inc. SYBX 11.19% (before the market open)
NovaBay Pharmaceuticals, Inc. NBY 9.31% (after the close)
Neoleukin Therapeutics, Inc. NLTX 2.44% (after the close)
OpGen, Inc. OPGN 3.89% (after the close)
Eyenovia, Inc. EYEN 0.47% (after the close)
HTG Molecular Diagnostics, Inc. HTGM 3.13% (after the close)
CymaBay Therapeutics, Inc. CBAY 5.24% (after the close)
BIOLASE, Inc. BIOL (after the close)
ADMA Biologics, Inc. ADMA 2.42% (after the close)
Athersys, Inc. ATHX 3.31% (after the close)

Other Events

On Wednesday, CytoDyn Inc. CYDY 4.83% will update shareholders on its recent COVID-19-related filings for conditional emergency use authorization with the FDA in the U.S., an interim order in Canada, and an accelerated rolling review in the U.K., as well as potential similar filings in Brazil and the Philippines. It will also provide updates on its active trials for COVID-19, non-alcoholic steatohepatitis and cancer treatments, along with expected timelines for BLA submissions for HIV in the U.S., Canada and the U.K.

IPOs

Dutch biotechnology Lava Therapeutics B.V. has filed to offer 6.7 million shares in an initial public offering to be priced between $14 and $16. The company has applied for listing on the Nasdaq under the ticker symbol LVTX. Lava develops biospecific antibodies engineered to induce immunity against tumor cells.

https://www.benzinga.com/general/biotech/21/03/20261034/fda-decisions-for-pfizer-eli-lilly-and-bluebird-bio-bristol-meyers-squibb-plus-new-data-and-earni

Disulfiram associated with lower risk of Covid-19

 Nathanael Fillmore,  

View ORCID ProfileSteven Bell, Ciyue Shen, Vinh Nguyen, Jennifer La, Maureen Dubreuil, Judith Strymish, Mary Brophy,  View ORCID ProfileGautam Mehta,  View ORCID ProfileHao Wu,  View ORCID ProfileJudy Lieberman, Nhan Do,  View ORCID ProfileChris Sander

doi: https://doi.org/10.1101/2021.03.10.21253331

This article is a preprint and has not been peer-reviewed [what does this mean?]. It reports new medical research that has yet to be evaluated and so should not be used to guide clinical practice.

https://www.medrxiv.org/content/10.1101/2021.03.10.21253331v1.full.pdf

ABSTRACT

In the global COVID-19 pandemic, there is a substantial need for effective, low-cost therapeutics. We investigated the potential effects of disulfiram on the incidence and outcomes of COVID-19 in an observational study in a large database of US Veterans Administration clinical records, the VA Corporate Data Warehouse (CDW). The study is motivated by the unique properties of disulfiram, which has been used as an anti-alcoholism drug since 1948, is non-toxic, easy to manufacture and inexpensive. Disulfiram reduces hyperinflammation in mammalian cells by inhibition of the gasdermin D pore. In a mouse model of sepsis, disulfiram reduced inflammatory cytokines and mortality. Disulfiram also is a low micromolar inhibitor of the Mpro and PLpro viral proteases of SARS-CoV-2.

To investigate the potential effects of disulfiram on the incidence and severity of COVID-19, we carried out an epidemiological study in the CDW. The VA dataset used has 944,127 patients tested for SARS-Cov-2, 167,327 with a positive test, and 2,233 on disulfiram, of which 188 had a positive SARS-Cov-2 test. A multivariable Cox regression adjusted for age, gender, race/ethnicity, region, a diagnosis of alcohol use disorders, and Charlson comorbidity score revealed a reduced incidence of COVID-19 with disulfiram use with a hazard ratio of 0.66 and 95% confidence interval of 0.57 to 0.76 (P < 0.001). There were no deaths among the 188 SARS-Cov-2 positive patients treated with disulfiram. The expected number of deaths would have been 5-6 according to the 3% death rate among the untreated (P-value 0.03).

Our finding of a lower hazard ratio and less severe outcomes for COVID-19 in patients treated with disulfiram compared to those not treated is a statistical association and does not prove any causative effect of disulfiram. However, the results of this study suggest that there is a pharmacological contribution to the reduced incidence and severity of COVID-19 with the use of disulfiram. Given the known anti-inflammatory and viral anti-protease effects of disulfiram, it is reasonable and urgent to initiate accelerated clinical trials to assess whether disulfiram reduces SARS-CoV-2 infection, disease severity and death.

Importance Identifying already approved medications with well characterized antiviral or anti-inflammatory properties supported by real world evidence as candidates for clinical trials for repurposing is an important strategy to manage the pandemic given the ongoing challenges with producing and administering vaccines, the emergence of more infectious viral mutants and the paucity of approved therapies.

Objective To investigate the potential effects of disulfiram on the incidence and severity of COVID-19.

Design Retrospective cohort study from February 20, 2020 to February 1, 2021.

Setting Veterans Health Administration. Veterans who had visited a VA primary care provider in the 18 months before their first SARS-CoV-2 test.

Participants 2,233 Veterans with at least one SARS-CoV-2 laboratory (positive or negative) test result on or after February 20, 2020 and at least one pharmacy record for disulfiram on or after February 20, 2019 and 941,894 Veterans without a pharmacy record for disulfiram.

Exposure Treatment with disulfiram

Main Outcome Positive test result for SARS-CoV-2

Results A multivariable Cox regression analysis adjusted for age, gender, race/ethnicity, region, diagnosis of an alcohol use disorder, and Charlson comorbidity score resulted in a reduced hazard of COVID-19 infection with disulfiram use, with a hazard ratio of 0.66 and 95% confidence interval of 0.57 to 0.76 (P < 0.001).

Conclusions and Relevance The results of this study suggest that disulfiram use contributes to a reduced incidence of COVID-19. Given the known anti-inflammatory and anti-protease effects of disulfiram, its low cost, low side effects, and general availability, it is reasonable and urgent to initiate accelerated clinical trials to assess the effect of disulfiram on infection and the development of advanced disease.

Competing Interest Statement

The authors have declared no competing interest.

Funding Statement

The work was supported by the British Heart Foundation RG/4/32218 (SB), the VA Boston Healthcare System (VA team), Dana-Farber Cancer Institute and Harvard Medical School (C.Shen, C.Sander).

https://www.medrxiv.org/content/10.1101/2021.03.10.21253331v1

International spectators to be barred from entering Japan for Olympics

 International spectators will not be allowed to enter Japan for this summer’s Olympic Games amid public concerns over coronavirus, organisers said on Saturday, setting the stage for a drastically scaled-back event.

Some 600,000 Olympic tickets purchased by overseas residents will be refunded, as will another 300,000 Paralympic tickets, Toshiro Muto, the chief executive of the Tokyo 2020 organising committee told a news conference.

He declined to say how much the refunds would cost.

The Olympic Games were postponed last year due to the COVID-19 pandemic. While the outbreak has chilled public opinion toward the event, both organisers and Prime Minister Yoshihide Suga have vowed to press ahead with the Games.

The decision on international spectators will “ensure safe and secure Games for all participants and the Japanese public,” Tokyo 2020 organisers said in a statement following five-way talks that included the head of the International Olympic Committee, Thomas Bach, and the Tokyo governor.

“People who are involved in the Olympics in some way may be allowed to enter the country, whereas regular visitors will not be able to,” Tokyo 2020’s Muto said.

He said costs for hotel cancellations would not be covered. Organisers may also consider cutting the number of staff members who will participate in the Games.

The Games are scheduled for July 23 to Aug. 8, and the Paralympics from Aug. 24 to Sept. 5.

Media polls have shown that a majority of the Japanese public are wary about letting in international spectators to watch the Games as the country grapples with the tail-end of a third wave of the pandemic.

STRIPPED-DOWN GAMES

A stripped-down Games means the government will not get the tourism boom it had long counted on. Japan has grown increasingly reliant on foreign tourists, particularly from Asia, to bolster its weak domestic economy.

Like other countries, it has seen tourism unravel with the pandemic and its hotels and restaurants have been hit hard.

Saturday’s decision did not cover local spectators. Muto said organisers will decide next month on caps for spectators in venues.

“It’s very unfortunate,” Tokyo Governor Yuriko Koike said of the decision on international spectators, speaking to reporters after the meeting.

But she added that the conclusion was “unavoidable” given that the main priority for holding a successful Games would be the health of the athletes and the Japanese public.

Kyodo news service earlier reported that organisers were leaning towards barring overseas volunteers from helping at the Games.

Sources told Reuters earlier this month that the Japanese government had concluded it will not be able to allow spectators from abroad.

https://www.reuters.com/article/us-olympics-2020/international-spectators-to-be-barred-from-entering-japan-for-olympics-idUSKBN2BC04K

China biotech Connect Biopharma prices upsized US IPO at $17 high end

 Connect Biopharma Holdings, a Chinese Phase 2 biotech developing therapies for T cell-driven inflammatory diseases, raised $191 million by offering 11.3 million ADSs at $17, the high end of the range of $15 to $17. The company offered 1.9 million more ADSs than anticipated. At pricing, Connect Biopharma commands a market value of $949 million.

The company's lead candidate, CBP-201, is an antibody designed to target interleukin-4 receptor alpha, a validated target for the treatment of inflammatory diseases such as atopic dermatitis (AD) and asthma. The company has initiated a Phase 2b trial of CBP-201 moderate-to-severe AD in the US, Australia, and New Zealand, with top-line results expected in the 2H21. Connect also plans to initiate additional trials in asthma and chronic rhinosinusitis with nasal polyps in the 1H21 and in AD patients in China in the 2H21.

Connect Biopharma Holdings plans to list on the Nasdaq under the symbol CNTB. Jefferies, SVB Leerink, Piper Sandler and CICC acted as lead managers on the deal.

https://www.nasdaq.com/articles/chinese-inflammatory-disease-biotech-connect-biopharma-prices-upsized-us-ipo-at-%2417-high

COVID-19 lockdowns and demographically-relevant Google Trends

 Google Trends reveal how searches related to family and relationship behaviors, such as weddings, contraception, and abortions, changed during lockdowns in the US and Europe.

###

Link to publicly available article:
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0248072

Funding: The authors received no specific funding for this work.

Competing Interests: The authors have declared that no competing interests exist.

Article URL:
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0248072

 E-MAIL

CAPTION

Event study estimates of associations of lockdown timing with Google searches for breakup and divorce. Event study estimation results. The model for Europe included 6 countries: Austria, France, Germany, Italy, Spain, and the United Kingdom. The estimation sample for the United States included the 42 States that implemented a lockdown + Washington D.C. See S2 Table for lockdown dates and States included in the estimation sample.

CREDIT

Berger et al, PLOS ONE, 2021 (CC-BY 4.0, https://creativecommons.org/licenses/by/4.0/)

https://www.eurekalert.org/pub_releases/2021-03/p-cla031821.php

Stroke risk higher than expected among COVID-19 patients

 New research found patients hospitalized with COVID-19 had a higher risk of stroke, compared with patients who had similar infectious conditions such as influenza and sepsis in prior studies. Those who had an ischemic stroke were more likely to be older, male, Black race, or have high blood pressure, Type 2 diabetes or an irregular heartbeat (atrial fibrillation) compared with other COVID-19 patients, according to late-breaking science presented today at the American Stroke Association's International Stroke Conference 2021. The meeting is being held virtually, March 17-19, 2021 and is a world premier meeting for researchers and clinicians dedicated to the science of stroke and brain health.

For this analysis, researchers accessed the American Heart Association's COVID-19 Cardiovascular Disease Registry to investigate stroke risk among patients hospitalized for COVID-19, their demographic characteristics, medical histories and in-hospital survival. The COVID-19 Registry data pulled for this study included more than 20,000 patients hospitalized with COVID-19 across the U.S. between January and November 2020.

"These findings suggest that COVID-19 may increase the risk for stroke, though the exact mechanism for this is still unknown," said lead study author Saate S. Shakil, M.D., a cardiology fellow at the University of Washington in Seattle. "As the pandemic continues, we are finding that coronavirus is not just a respiratory illness, but a vascular disease that can affect many organ systems."

Two hundred eighty-one people (1.4%) in the COVID-19 CVD Registry had a stroke confirmed by diagnostic imaging during hospitalization. Of these, 148 patients (52.7%) experienced ischemic stroke; 7 patients (2.5%) had transient ischemic attack (TIA); and 127 patients (45.2%) experienced a bleeding stroke or unspecified type of stroke.

The analysis of COVID-19 patients also found:

• Those with any type of stroke were more likely to be male (64%) and older (average age 65) than patients without stroke (average age 61);
• 44% of patients who had an ischemic stroke also had Type 2 diabetes vs. about one-third of patients without stroke, and most of the ischemic stroke patients had high blood pressure (80%) compared to patients without stroke (58%);
• 18% of ischemic stroke patients had atrial fibrillation, while 9% of those without stroke also had atrial fibrillation;
• Patients who had a stroke spent an average of 22 days in the hospital, compared to 10 days of hospitalization for patients without stroke; and
• In-hospital deaths were more than twice as high among stroke patients (37%) compared to patients without stroke (16%).

In addition, stroke risk varied by race. Black patients accounted for 27% of the patients in the COVID-19 CVD Registry pool for this analysis; however, 31% of ischemic stroke cases were among Black patients.

"We know the COVID-19 pandemic has disproportionately affected communities of color, but our research suggests Black Americans may have higher risk of ischemic stroke after contracting the virus, as well," Shakil said. "Stroke on its own can have devastating consequences and recovering from COVID-19 is often a difficult path for those who survive. Together, they can exact a significant toll on patients who have had both conditions."

Shakil added, "It is more important than ever that we curb the spread of COVID-19 via public health interventions and widespread vaccine distribution."

###

In April 2020, the American Heart Association created the COVID-19 CVD Registry within weeks of the declaration of the global pandemic to rapidly collect and provide insights into patients hospitalized with the novel coronavirus. The Association's robust Get With the Guidelines registry infrastructure has allowed for rapid data collection, including over 37,000 patient records and more than 135,000 lab reports, with more than 160 registry sites enrolled (data as of 2/23/21).

Co-authors are Sophia Emmons-Bell, B.A.; Christine Rutan, B.A.; Jason Walchok, B.A., N.R.P.; James A. de Lemos, M.D.; Babak Navi, M.D., M.S.; Alexander E. Merkler, M.D., M.S.; Gregory A. Roth, M.D., M.P.H.; and Mitchell S.V. Elkind, M.D., M.S., FAHA, FAAN. Disclosures are available in the abstract.

This study was funded by the American Heart Association.

https://www.eurekalert.org/pub_releases/2021-03/aha-srh031921.php