Moderna discusses COVID-19 vaccine manufacturing with Nexus

 Moderna Inc, looking to boost production of its COVID-19 vaccine, met with Nexus Pharmaceuticals to discuss manufacturing the shot at the company's new plant in Wisconsin, which has the capacity to process and fill 30 million doses a month, sources with knowledge of the matter said.

The meeting between Moderna and the maker of specialty drugs took place on Tuesday, the sources said.

Senior White House and administration officials, including David Kessler, chief science officer for Covid response and Tim Manning, COVID-19 supply coordinator, have facilitated introductions and discussions between Nexus, Moderna and Johnson & Johnson, according to two sources.

Even though President Joe Biden has said there would be enough vaccines for all adults in the United States by May, there could still be supply concerns later in the year, particularly if people require a booster shot at some point to protect against concerning virus variants that may be circulating.

It remains unclear if the meeting will result in a deal to manufacture vaccines at the Nexus plant, the sources said. Funding from the Defense Production Act will be essential for a deal to work, one of the sources said.

"Moderna is looking to produce more vaccines ... and Nexus has the capacity to do it," one of the sources said.

Illinois-based Nexus does not currently manufacture COVID-19 vaccines but has built capacity to ramp up production at their new plant in Wisconsin, one of the sources said.

The White House declined comment on the meeting. Nexus and Moderna also declined comment.

On Tuesday, Moderna said it was on track to deliver 300 million doses to the United States by the end of July, in line with its commitments. Moderna delivered 45 million vaccines to U.S. states in March.

Moderna's chief executive on Wednesday said the company was unlikely to markedly speed up its vaccine production in the next few months, though it expects the output to have increased significantly by 2022.

The Biden administration has previously brokered commitments among rival drugmakers to boost COVID-19 vaccine production.

In March, Biden announced that Merck & Co will help manufacture Johnson & Johnson's single-shot coronavirus vaccine.

Despite its efforts there have been significant setbacks.

For example, some 15 million doses of J&J's vaccine were wasted due to contamination with ingredients from AstraZeneca's shot at a Baltimore plant that was producing both. That Emergent BioSolutions facility will now produce only the J&J shot.

Separately, U.S. federal health agencies on Tuesday recommended pausing use of the J&J COVID-19 vaccine while it looks into six cases of rare brain blood clots in women under age 50 who received the shot.

https://news.yahoo.com/moderna-discusses-covid-19-vaccine-194029809.html

Thermo Fisher in late talks to buy PPD for over $15B

 Medical device company Thermo Fisher Scientific is nearing a deal to buy contract research firm PPD Inc for more than $15 billion, the Wall Street Journal reported on Wednesday, citing people familiar with the matter.

The companies could finalize a deal as soon as this week, the report said. 

Shares of PPD closed 12% higher at $43, while Thermo Fisher fell 1.4% to $478.

PPD provides clinical development and laboratory services to pharmaceutical, biotechnology, medical device and government organizations. It has a market capitalization of $13.4 billion, according to Refinitiv data.

https://www.reuters.com/article/us-ppd-m-a-thermo-fisher/thermo-fisher-in-late-talks-to-buy-ppd-for-over-15-billion-wsj-idUSKBN2C12SQ

Skin injection could allow vaccination of up to 5X more people from same supplies

 The current COVID-19 vaccination campaign involves injecting the vaccine into muscle tissue, but injecting a smaller amount of vaccine in the skin might also provide good protection. The #wakeuptocorona crowdfunding campaign has enabled Anna Roukens (LUMC) to examine the safety and efficacy of vaccination delivery via the skin.

The #wakeuptocorona crowdfunding campaign was launched just over a year ago, but has already exceeded the one million euro mark and is still underway. The funding facilitated an extension to the laboratory of Professor of Virology Eric Snijder (LUMC), and has also enabled a great deal more coronavirus research to be conducted. This month Anna Roukens, an internist and infectious disease specialist at LUMC, will begin research on Moderna vaccine delivery via the skin.

What advantage does skin vaccination offer compared with regular vaccination?

Roukens: A huge problem is that there are currently not enough supplies to vaccinate everyone at the same time. With skin vaccination, we can vaccinate more people using the same amount of vaccine. This means people would be vaccinated sooner.

Is this a new method?

No, skin vaccination isn't new. We have been using this method for some time now for rabies and yellow fever vaccinations. It is an excellent way to use the vaccine as sparingly as possible. We now want to find out whether the Moderna vaccine is also suitable for immunization via the skin. We first plan to test its safety and will then work out how much vaccine is needed to provide good protection.

So how does vaccination via the skin work?

The skin is full of dendritic cells, which act as the guards of the immune system. When they detect a virus, they warn other immune cells, which go on to attack the virus. Skin vaccination involves delivering a small amount of the vaccine precisely where these guards are located. This ensures that no vaccine is wasted. The dendritic cells absorb the vaccine and initiate the immune response. This should ultimately protect us against coronavirus.

Will we soon be using skin vaccinations?

Possibly, but possibly not. We hope to speed up the Dutch vaccination campaign, but we are not yet sure whether the results will be available before the end of the first round of vaccinations. What we do expect, however, is more frequent coronavirus outbreaks. Moreover, almost no vaccines have yet been administered in poor countries. So we are definitely not done with vaccinations yet.

What role did #wakeuptocorona play in setting up the research?

The money raised by the campaign has been extremely important! Without the 40,000 euros from the campaign, we wouldn't have been able to start the research. We still need more money, but thanks to crowdfunding, we can now demonstrate the safety of skin vaccination. Hopefully this will help persuade even more people to donate.

What would you like to say to the 6,400 #wakeuptocorona supporters?

It's thanks to all these supporters that we can do a great deal of beneficial work. There is another major COVID-19 research , for example, in which 14 different LUMC laboratories are working together, each making use of its own expertise. This cooperation would not have been possible without their donations to the campaign. Moreover, if skin vaccination with the Moderna vaccine is effective, it will be an important step in tackling the pandemic.

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Explore further

Skin reactions usually mild after COVID-19 vaccination

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More information: #wakeuptocorona crowdfunding campaign: www.steunleiden.nl/project/wakeuptocorona

https://medicalxpress.com/news/2021-04-skin-vaccination-people.html

Mystery canine illness identified as animal coronavirus

 An outbreak of vomiting among dogs has been traced back to a type of animal coronavirus by researchers.

Vets across the country began reporting cases of acute onset prolific vomiting in 2019/20.

The Small Animal Veterinary Surveillance Network (SAVSNet) at the University of Liverpool asked vets for help in collecting data, with 1,258 case questionnaires from vets and owners plus 95 clinical samples from 71 animals.

Based on this data, a team from the universities of Liverpool, Lancaster, Manchester and Bristol identified the outbreak as most likely to be a variant of canine enteric coronavirus (CeCoV).

Canine coronavirus only affects dogs and is not the same as SARS-Cov-2, which causes COVID-19 in humans. Researchers found no evidence of any similar illness in people.

The work is published in Emerging Infectious Diseases.

The team are working on a project funded by the Dogs Trust called SAVSNet-Agile which aims to develop a national surveillance system for canine health.

Dr. Barry Rowlingson from Lancaster University said: "We've developed complex statistical models to look for disease outbreaks. Being able to rapidly detect increased incidence, without triggering a false alarm from a natural random variation, is the key problem here. Early detection is crucial to early treatment and enhanced monitoring.

"The SAVSNet Agile project aims to feed information back to local veterinary practices so they can be alert to any new outbreaks."

Vets began to suspect an infectious cause because vomiting was more frequent than is typical for canine gastroenteritis.

SAVSNet researchers found a specific and significant increase in the number of dogs recorded as exhibiting gastroenteric signs between late December 2019 and March 2020.

As well as reusing health records, SAVSNet also collected questionnaire data from vets and owners caring for affected animals, as well as healthy controls. This showed male dogs were more at risk than females.

Charlotte Appleton, SAVSNet Agile Ph.D. Student, said: "Obtaining such important results at an early stage of my Ph.D. is a wonderful achievement and will hopefully provide a pathway of higher visibility into the health of domestic animals."

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Explore further

Canine babesiosis outbreak in UK under control—but needs monitoring

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More information: Alan D. Radford et al. Outbreak of Severe Vomiting in Dogs Associated with a Canine Enteric Coronavirus, United Kingdom, Emerging Infectious Diseases (2021). DOI: 10.3201/eid2702.202452

https://phys.org/news/2021-04-mystery-canine-illness-animal-coronavirus.html

Headache During COVID-19

 Edoardo Caronna MD; Patricia Pozo-Rosich MD, PhD

DISCLOSURES 

Headache. 2021;61(2):385-386. 

The year 2020 will forever be remembered as the year characterized by a new global pandemic, COVID-19, caused by the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). In every scientific field, this new pathogen has represented the opportunity for either describing unknown disease presentations or re-assessing others from a new perspective.

So, what have we learned about headache, and, how should these lessons help redefine our comprehension and definition of 9.2.2 Headache attributed to systemic viral infection in the International Classification of Headache Disorders (ICHD)?^[1]

Headache is one of the most common^[2] and disabling neurological symptoms of COVID-19, underlying a direct attack of SARS-CoV-2 on the trigeminovascular system, via transynaptic or bloodstream dissemination,^[3] and/or immuno-mediated inflammatory responses^[4] that act as well on the central nervous system. Other viruses, when sharing these characteristics, may cause headache as a predominant symptom; however, detailed studies are lacking in the field and should be implemented.

Headache associated with COVID-19 has multiple phenotypes. In almost 25% of patients, headache is severe with migraine-like features while the rest has a less intense pain probably more similar to the characteristics of tension-type headache.^[5] Interestingly, this migraine-like phenotype is observed in other studies;^[6,7] however, there is no significant association between its presence and prior migraine history.^[5,6] So, potentially, anyone could experience headache similar to a migraine attack in the context of the pandemic, reflecting an activation of the trigeminovascular system.

Our experience with COVID-19 reinforces several important concepts of headache pathophysiology:

1. Headache is the result of complex mechanisms involving (a) genetic predisposition, (b) the activation of the trigeminovascular system, (c) individual clinical characteristics (age, gender, comorbidities, etc.), and (d) the pathogen itself, its neuro-invasive potential, and ability to produce inflammation at a systemic or a more localized level;

2. Primary and secondary headache disorders share common pathophysiological mechanisms. It is interesting to notice that this is also observed in other secondary headaches caused by completely different noxae, such as, post-traumatic headache.

The ICHD not only guides clinicians in the diagnosis of headache but also offers researchers a more systematic approach to study different headache types. In this regard, we believe that the next ICHD should try to provide a more pathophysiological-driven classification based on clinical characteristics. This would be a relevant conceptual change, considering that each phenotype probably reflects different pathophysiological mechanisms which might be correlated with different treatment responses. 9.2.2 Headache attributed to systemic viral infection in the ICHD, for example, could include these different phenotypes as an alternative for criterion C.4 and when coding this diagnosis specify if it is migraine-like or tension-type-like.

In the near future, we hope COVID-19 will also serve as an opportunity to regain interest in elucidating not only "headache attributed to systemic viral infection" pathophysiologically but also secondary headache in general.

https://www.medscape.com/viewarticle/946824

Nurix started as Buy by Berenberg

https://finviz.com/quote.ashx?t=NRIX

Nurix Q1 Fiscal 2021 Financial Results, Corporate Update

 On track to initiate Phase 1 trials for four wholly owned drug candidates in 2021

Expanded Sanofi collaboration resulting in option exercise payment of $22 million

Strong financial position after successful $150 million follow-on offering in March 2021

Recent Business Highlights

• Expanded Strategic Collaboration with Sanofi S.A. (Sanofi): On January 7, 2021, Nurix announced the expansion of its global strategic collaboration with Sanofi to discover, develop and commercialize a pipeline of innovative targeted protein degradation drugs for patients with challenging diseases in multiple therapeutic areas. Sanofi has exercised its option to expand the number of targets in the collaboration agreement from three to a total of five targets. With the expansion, Nurix received a payment of $22 million, in addition to the previously received upfront payment of $55 million.
  
• Completed a Public Follow-on Offering: On March 9, 2021, Nurix announced the closing of its underwritten public offering of 5,175,000 shares of common stock, at a public offering price of $31.00 per share, which included 675,000 shares issued upon the exercise in full by the underwriters of their option to purchase additional shares of common stock. The net proceeds to Nurix from the offering were approximately $150 million, after deducting underwriting discounts, commissions and offering expenses.
  
• Presented Preclinical Data Highlighting NX-1607: Nurix presented data from its NX-1607 program at the American Association for Cancer Research 2021 annual meeting which is being held virtually over two weeks, April 10-15 and May 17-21. NX-1607, an orally bioavailable, small-molecule inhibitor of Casitas B-lineage lymphoma B (CBL-B), demonstrated significant anti-tumor efficacy in animal models of both colorectal cancer and triple negative breast cancer. Importantly, the combination of NX-1607 and an anti-PD-1 antibody substantially increased the median overall survival and the frequency of long-lasting tumor rejection in these models compared to either single agent alone. The activity of NX-1607 was shown to be dependent on CD8+ T cells and NK cells. A copy of the poster can be found on Nurix’s website (link).
  
• Announced Collaboration for the Discovery of Novel Drugs to Treat Pediatric Cancers: On March 16, 2021, Nurix announced that it is part of a collaboration sponsored by Alex’s Lemonade Stand Foundation (ALSF), a leading funder of pediatric cancer research, to develop a drug to potentially treat aggressive childhood cancers including neuroblastoma and medulloblastoma. Nurix will provide its extensive expertise in E3 ligases and use its proprietary DNA-encoded library to help identify small-molecule degraders of MYCN, a target previously considered undruggable. The program is one of four that are being supported by ALFS’s Crazy 8 initiative, which is designed to bring together world-class research talent to accelerate the pace of new cure discovery in childhood cancer.

Upcoming Program Highlights

• NX-2127: Nurix’s lead drug candidate from its protein degradation portfolio, NX-2127, is an orally available degrader of Bruton’s tyrosine kinase (BTK) with immunomodulatory drug (IMiD) activity for the treatment of relapsed or refractory B-cell malignancies. Nurix filed an IND for NX-2127 in December 2020 and received clearance by the U.S. FDA to initiate human clinical trials. Clinical sites are actively recruiting patients for a Phase 1 clinical trial of NX-2127. Additional information on the clinical trial can be accessed at ClinicalTrials.gov (NCT04830137).
  
• NX-1607: Nurix’s lead drug candidate from its E3 ligase inhibitor portfolio, NX-1607, is an orally available inhibitor of CBL-B for immuno-oncology indications. Nurix anticipates initiating a Phase 1 trial for NX-1607 in the second half of 2021 (expected timing of events here and throughout the press release are based on calendar year quarters).
  
• NX-5948: Nurix’s second drug candidate from its protein degradation portfolio, NX-5948, is an orally available BTK degrader designed without IMiD activity for certain B-cell malignancies, autoimmune diseases and related diseases such as graft-versus-host disease. Nurix recently disclosed that NX-5948 crosses the blood brain barrier in animal models, further differentiating it from NX-2127. NX-5948 has also demonstrated potent anti-inflammatory activity in an animal model of rheumatoid arthritis. Nurix anticipates initiating a Phase 1 trial for NX-5948 in patients with hematologic malignancies in the second half of 2021.
  
• DeTIL-0255: Nurix’s lead candidate in its cellular therapy portfolio, DeTIL-0255, is a drug-enhanced adoptive cellular therapy. Nurix anticipates initiating a Phase 1 trial for DeTIL-0255 in the second half of 2021.

https://www.globenewswire.com/news-release/2021/04/13/2209501/0/en/Nurix-Therapeutics-Reports-First-Quarter-Fiscal-2021-Financial-Results-and-Provides-a-Corporate-Update.html