Evotec launches 'PRROTECT', pre-competitive initiative to be better prepared for future pandemics

  . INTEGRATED PLATFORM APPROACH TO RESPOND TO THE CHALLENGES OF PANDEMIC PREPAREDNESS, RAPID RESPONSE AND

    DELIVERABILITY 
  . PRROTECT COMBINES FIRST-IN-CLASS PROGRAMMES ACROSS THERAPEUTIC MODALITIES, ACCELERATED R&D TIMELINES FOR HIGHLY 
    EFFECTIVE NEUTRALISING ANTIBODIES WITH AI/ML PREDICTION TOOLS (J.HAL^?) AND MANUFACTURING PLATFORM (J.POD^(R)) 
 
Evotec SE (Frankfurt Stock Exchange: EVT, MDAX/TecDAX, ISIN: DE0005664809) announced today that the Company has 
launched an initiative for pandemic preparedness ("PRROTECT"). PRROTECT leverages a comprehensive set of novel projects 
and technologies to be better prepared for and respond faster to viral pandemics of the future. 
Virus outbreaks that can develop into dynamic pandemics are a permanent global threat. Besides preventive measures and 
vaccines, highly effective therapeutics are the backbone of any pandemic response. Evotec's PRROTECT initiative 
includes the development and delivery of superior novel therapeutics to curb the next viral pandemic. Based on the 
Company's distinctive set of global capabilities, Evotec is uniquely positioned to develop next-generation therapeutics 
across all modalities including small molecules, protein degraders, antibodies and immuno-modulators, but excluding 
vaccines. 
PRROTECT will be an open pre-competitive network initiative designed to offer the best protection against future 
pandemics by including three lines of preparation: 
  . Preparedness against viral threats, i.e. the pre-development of a multimodality pipeline of therapeutic candidates 
    against the most threatening viruses as defined by the World Health Organisation ("WHO") 
  . Rapid response technologies to accelerate de novo R&D timelines of highly effective neutralising antibodies using 
    AI & ML platforms (e.g. J.HAL^?) 
  . Flexible manufacturing network with highly intensified production facilities (J.POD^(R)) to provide therapeutic 
    antibodies quickly wherever needed 

https://www.marketscreener.com/quote/stock/EVOTEC-SE-436047/news/PRESS-RELEASE-nbsp-Evotec-launches-PRROTECT-a-pre-competitive-initiative-to-be-better-prepared-35605232/

AstraZeneca: Covid-19 Vaccine Is 92% Effective Against Indian Variant

 AstraZeneca PLC said Tuesday that its Covid-19 vaccine is 92% effective against hospitalizations of the Delta, or Indian, variant after two shots, without any deaths.

The pharmaceutical giant also said the vaccine is 86% effective in reducing hospitalizations in the Alpha, or Kent, variant with no deaths reported.

Vaccine effectiveness against symptomatic disease was 74% against the Alpha variant and 64% against the Delta variant, AstraZeneca added.

"The data show that the vaccine will continue to have a significant impact around the world given that it continues to account for the overwhelming majority of supplies to India and the Covax facility," Executive Vice President, BioPharmaceuticals R&D Mene Pangalos said.

https://www.marketscreener.com/quote/stock/ASTRAZENECA-PLC-4000930/news/AstraZeneca-nbsp-Covid-19-Vaccine-Is-92-Effective-Against-Indian-Variant-35605691/

AstraZeneca: AZD7442 Trial for Prevention of Symptomatic Covid-19 Didn't Meet Primary Goal

 AstraZeneca PLC said Tuesday that a Phase 3 trial to assess the safety and efficacy of a long-acting antibody combination called AZD7442 for the prevention of symptomatic Covid-19 after exposure didn't meet the primary goal.

The Cambridge, U.K.-based pharmaceutical company said AZD7442 reduced the risk of developing symptomatic Covid-19 in unvaccinated adults with confirmed exposure to a person with a case of the SARS-CoV-2 virus within the past eight days by 33% compared with placebo, which wasn't statistically significant.

However, in patients who were polymerase chain reaction, or PCR, negative at the time of dosing, AZD7442 reduced the risk of developing symptomatic Covid-19 by 92% compared with placebo more than seven days following dosing, which suggests that the drug may be useful in preventing symptoms in individuals not already infected, AstraZeneca said.

"While this trial did not meet the primary endpoint against symptomatic illness, we are encouraged by the protection seen in the PCR negative participants following treatment with AZD7442," AstraZeneca's BioPharmaceuticals R&D Executive Vice President Mene Pangalos said.

The company in March said it had extended an agreement with the U.S. government to supply up to 500,000 additional doses of AZD7442 for $205 million, contingent on AZD7442 receiving emergency-use authorization from the U.S. Food and Drug Administration. Discussions with the U.S. government regarding next steps are continuing, AstraZeneca said.

https://www.marketscreener.com/quote/stock/ASTRAZENECA-PLC-4000930/news/AstraZeneca-nbsp-AZD7442-Trial-for-Prevention-of-Symptomatic-Covid-19-Didn-t-Meet-Primary-Goal-35605727/

ResMed Rises as Royal Philips Recalls Sleep Apnea Devices

 ResMed  (RMD) - Get Report shares rose on Monday after a rival to the medical-device maker, Royal Philips, recalled 3.5 million ventilation devices for treating sleep apnea.

Needham analyst Mike Matson, who has a buy rating and a $229 price target on ResMed, said the recall would help ResMed, though the exact effect is hard to calculate, Bloomberg reports.

ResMed shares recently traded at $228.92, up 4.7%. The stock has surged 24% over the past three months.

Some patients using the Philips ventilators might shift to RMD while their products are getting repaired, Matson said. He added that the repairs will likely take at least several months.

Users with certain insurance can substitute a ResMed device for their Royal Philips device, if that device is older than five years, he said.

In other health-care news Monday, ITeos Therapeutics  (ITOS) - Get Report shares leaped after the drug creator said GlaxoSmithKline GSK would pay up to $2.1 billion for it to develop cancer drugs.

The Cambridge, Mass., company and Glaxo unveiled a deal to co-develop and co-commercialize EOS-448, a monoclonal antibody in Phase 1 development as a potential treatment for patients with cancer.

Under terms of the deal, ITeos will receive $625 million up front. ITeos will then be eligible to receive as much as $1.45 billion in milestone payments.

Last week, analysts upgraded Biogen  (BIIB) - Get Report after the Food and Drug Administration's cleared its Alzheimer's treatment, aducanumab.

Bernstein’s Ronny Gal lifted his rating on the Cambridge, Mass., company to outperform from market perform. He set his price target at $500.

https://www.thestreet.com/investing/resmed-higher-after-royal-philips-recalls-sleep-apnea-device7

Novavax Vs. Pfizer Vs. Moderna: How COVID-19 Vaccines Stack Up

 It was "better late than never" for Novavax, Inc. 

NVAX 0.94%, as the biopharma finally got around to announcing interim results from the U.S. and Mexico leg of the Phase 3 study of NVX-CoV2371, its vaccine candidate against the novel coronavirus.

Here's a comparative perspective of the vaccine candidates from Novavax, and the frontrunners, namely Pfizer Inc. PFE 1.25%-BioNTech SE BNTX 7.53% and Moderna, Inc. MRNA 5.23%, both of which have authorized vaccines in the market.

Vaccine Type: Novavax's NVX-CoV2371 is a recombinant nano-particle protein-based COVID-19 vaccine that is packaged with the company's proprietary Matrix-M adjuvant.

The Pfizer-BioNTech and Moderna products are mRNA vaccines, or modern vaccines that work by using a genetic code called mRNA that instructs our immune cells to make spike protein, which is found on the surface of the virus that causes COVID-19.

This spike protein, though harmless, is capable of triggering our immune system to produce antibodies that offer protection against future infection.

Novavax's vaccine is a protein adjuvant that contains the spike protein of the coronavirus itself, but formulated as a nanoparticle that cannot cause disease. The injected vaccine then stimulates the immune system to produce antibodies and T-cell immune responses.

The Vaccine Doses: The vaccines from each of the three companies require two doses. Each dose consists of 30 mcg for Pfizer and 100 mcg for Moderna, while for Novavax, each vaccine dose consists of 5 mcg of NVX-CoV2371 and 50 mcg of Matrix-M1 adjuvant that are co-formulated.

The interval between the two doses — the priming and booster dose — is 21 days each for Pfizer and Novavax and 28 days for Moderna.

The Target Population: The original late-stage trial of Pfizer-BioNTech evaluated the vaccine in participants ages 16 years and older. The trial enrolled 43,448 participants.

Moderna's Phase 3 COVE study enrolled 30,000 participants ages 18 years and up. 

Since then, these two companies have obtained authorizations for their respective vaccines to be used in adolescents.

Both companies have also initiated studies in the pediatric population.

Novavax's study enrolled 29,960 participants 18 years of age and older across 119 sites in the U.S. and Mexico. The placebo-controlled portion of PREVENT-19 continues in adolescents from 12 to less than 18 years of age and recently completed enrollment with 2,248 participants.

Vaccine Logistics: Pfizer recently secured FDA authorization for storing undiluted, thawed vaccine vials in the refrigerator at 2°C to 8°C for up to one month.

Previously, thawed, undiluted vaccine vials could be stored in the refrigerator for up to five days. Moderna's vaccine can be stored refrigerated between 2° and 8°C for up to 30 days prior to first use.

NVX-CoV2373 is stored and stable at 2°- 8°C, allowing the use of existing vaccine supply chain channels for its distribution. It is packaged in a ready-to-use liquid formulation in 10-dose vials.

Vaccine Efficacy: Interim data from Pfizer-BioNTech's Phase 3 trials released in December showed the vaccine was well-tolerated and demonstrated 95% efficacy in preventing COVID-19 in those without prior infection seven days or more after the second dose. Updated top-line results released for up to six months after the second dose confirmed efficacy at 91.3%.

The vaccine was found 100% effective against severe disease as defined by the U.S. Centers for Disease Control and Prevention, and 95.3% effective against severe COVID-19 as defined by the FDA. It was also proved effective against the U.K. strain in lab studies.

Moderna's vaccine showed efficacy of 94.1% against COVID-19. The company announced in May initial data from its Phase 2 study showing that a single 50 mcg dose of mRNA-1273 or mRNA-1273.351 given as a booster to previously vaccinated individuals increased neutralizing antibody titer responses against SARS-CoV-2 and two variants of concern, B.1.351, first identified in South Africa, and P.1, first identified in Brazil.

Novavax's investigational vaccine demonstrated 100% protection against moderate and severe disease not involving variants of concern or variants of interest.

Against variants of concern and variants of interest, the efficacy was 93.2% and in high-risk populations, defined as over 65 or under 65 years with certain comorbidities or having circumstances with frequent COVID-19 exposure, the efficacy was 91%.

Overall efficacy was 90.4%, meeting the primary endpoint.

Cantor Fitzgerald On Novavax's Vaccine: A differentiating factor for NVX-2373 is that it showed vaccine efficacy of 93.2% against VoC/VoI, which demonstrates protection across a broad range of SARS-CoV-2 strains, Cantor Fitzgerald analyst Charles Duncan said in a Monday morning note.

"Overall, these results enhance our conviction for a differentiated clinical and logistics profile from the SARS-CoV-2 vaccine candidate ‘2373," the analyst said.

Showing efficacy against new strains in two Phase 3 clinical trials, rather than extrapolating potential efficacy from a neutralizing antibody assay conducted in a petri dish, differentiates NVX-CoV2373 from other vaccines that have emergency use authorization, he said. 

This profile, according to Cantor reduces regulatory/ commercial risk for the ‘2373 SARS-CoV-2 prophylactic vaccine candidate and, with positive Phase 3 data for NanoFlu reported in March 2020, should raise the profile for Novavax's platform as a whole.

Vaccine Safety Data: Pfizer-BioNTech's vaccine showed a favorable tolerability and safety profile, with the most common adverse events from BNT162b2 being transient, mild to moderate pain at the injection site, fatigue and headache, and these generally resolved within two days.

For Moderna, the most common adverse reactions included injection site pain, fatigue, myalgia, arthralgia, headache, and erythema/redness at the injection site. Solicited adverse reactions increased in frequency and severity in the mRNA-1273 group after the second dose.

Preliminary safety data from Novavax's trial showed the vaccine to be generally well-tolerated. Serious and severe adverse events were low in number and balanced between vaccine and placebo groups.
In assessing reactogenicity seven days after dose one and dose two, injection site pain and tenderness, generally mild to moderate in severity, were the most common local symptoms, lasting less than three days. Fatigue, headache and muscle pain were the most common systemic symptoms, lasting less than two days.

https://www.benzinga.com/general/biotech/21/06/21551364/novavax-vs-pfizer-vs-moderna-how-covid-19-vaccines-stack-up

Extra COVID vaccine may help protect transplant patients

 A small study offers the first hint that an extra dose of COVID-19 vaccines just might give some organ transplant recipients a needed boost in protection.

Even as most vaccinated people celebrate a return to near normalcy, millions who take immune-suppressing medicines because of transplants, cancer or other disorders remain in limbo — uncertain how protected they really are. It’s simply harder for vaccines to rev up a weak immune system.

Monday’s study tracked just 30 transplant patients but it’s an important step toward learning if booster doses could help.

It didn’t help everybody. But of the 24 patients who appeared to have no protection after the routine two vaccinations, eight of them — a third — developed some virus-fighting antibodies after an extra shot, researchers from Johns Hopkins University reported in Annals of Internal Medicine. And six others who’d had only minimal antibodies all got a big boost from the third dose.

“It’s very encouraging,” said Dr. Dorry Segev, a Hopkins transplant surgeon who helped lead the research. “Just because you’re fully negative after two doses doesn’t mean that there’s no hope.”

Next up: Working with the National Institutes of Health, Segev’s team hopes to begin a more rigorous test of a third vaccination in 200 transplant recipients this summer.

For transplant patients, powerful immune-suppressing drugs prevent rejection of their new organs but also leave them extremely vulnerable to the coronavirus. They were excluded from initial testing of the COVID-19 vaccines, but doctors urge that they get vaccinated in hopes of at least some protection.

Some do benefit. The Hopkins team recently tested more than 650 transplant recipients and found about 54% harbored virus-fighting antibodies after two doses of the Pfizer or Moderna vaccines — although generally less than in otherwise healthy vaccinated people.

It’s not just a concern after organ transplants. One study of patients with rheumatoid arthritis, lupus and other autoimmune disorders found 85% developed antibodies, said Dr. Alfred Kim of Washington University in St. Louis. But those who used particular kinds of immune-suppressing drugs produced dramatically lower levels that are a cause for concern.

“We tell our patients to act like the vaccine is not going to work as well as it does for their family and friends,” said Kim, who would like to test a third dose in autoimmune patients, too. “This is very frustrating news to them.”

Doctors sometimes give extra doses of other vaccines, such as the hepatitis B shot, to people with weak immune systems.

And guidelines issued in France recommend a third COVID-19 shot for certain severely immune-suppressed people, including transplant recipients, Segev noted.

The U.S. hasn’t authorized extra COVID-19 vaccinations. But around the country, a growing number of immune-compromised patients are seeking third doses on their own — the people Hopkins sought to test.

In San Francisco, Gillian Ladd agreed to blood tests before and after an extra dose. The recipient of a kidney and pancreas transplant, Ladd, 48, was terrified to leave her house after learning she had no measurable antibodies despite two Pfizer shots.

With the additional dose, “I had gotten what I needed in order to survive,” Ladd said, but she’s still is sticking with masks and other precautions.

“I am being as careful as I possibly can while acknowledging that I’m coming back into the world of the living,” she said.

Further research is needed to tell if a third dose really helps, who’s the best candidate and if there are brand differences — plus whether the extra immune stimulation could increase the risk of organ rejection.

But Segev cautions boosters aren’t the only possibility. In addition to antibodies, vaccinations normally spur other protections such as T cells that can fend off severe illness. He and several other research groups are testing whether immune-compromised patients get that benefit.

For now, “the best way to protect these people is for others to get vaccinated” so they’re less likely to get exposed to the coronavirus, stressed Washington University’s Kim.

https://apnews.com/article/science-coronavirus-pandemic-health-222df4dfcb880ce9db3f3f1bc17185a1

Covid immunity will be long-lasting: Studies

 Generating immunity against the SARS-CoV-2 coronavirus is of the utmost importance for bringing the COVID-19 pandemic under control, protecting vulnerable individuals from severe disease and limiting viral spread. Our immune systems protect against SARS-CoV-2 either through a sophisticated reaction to infection or in response to vaccination. A key question is, how long does this immunity last? Writing in Nature, Turner et al.1 and Wang et al.2 characterize human immune responses to SARS-CoV-2 infection over the course of a year.

There is ongoing discussion about which aspects of the immune response to SARS-CoV-2 provide hallmarks of immunity (in other words, correlates of immunological protection). However, there is probably a consensus that the two main pillars of an antiviral response are immune cells called cytotoxic T cells, which can selectively eliminate infected cells, and neutralizing antibodies, a type of antibody that prevents a virus from infecting cells, and that is secreted by immune cells called plasma cells. A third pillar of an effective immune response would be the generation of T helper cells, which are specific for the virus and coordinate the immune reaction. Crucially, these latter cells are required for generating immunological memory — in particular, for orchestrating the emergence of long-lived plasma cells3, which continue to secrete antiviral antibodies even when the virus has gone.

Immunological memory is not a long-lasting version of the immediate immune reaction to a particular virus; rather, it is a distinct aspect of the immune system. In the memory phase of an immune response, B and T cells that are specific for a virus are maintained in a state of dormancy, but are poised to spring into action if they encounter the virus again or a vaccine that represents it. These memory B and T cells arise from cells activated in the initial immune reaction. The cells undergo changes to their chromosomal DNA, termed epigenetic modifications, that enable them to react rapidly to subsequent signs of infection and drive responses geared to eliminating the disease-causing agent4. B cells have a dual role in immunity: they produce antibodies that can recognize viral proteins, and they can present parts of these proteins to specific T cells or develop into plasma cells that secrete antibodies in large quantities. About 25 years ago5, it became evident that plasma cells can become memory cells themselves, and can secrete antibodies for long-lasting protection. Memory plasma cells can be maintained for decades, if not a lifetime, in the bone marrow6.

The presence in the bone marrow of long-lived, antibody-secreting memory plasma cells is probably the best available predictor of long-lasting immunity. For SARS-CoV-2, most studies so far have analysed the acute phase of the immune response, which spans a few months after infection, and have monitored T cells, B cells and secreted antibodies7. It has remained unclear whether the response generates long-lived memory plasma cells that secrete antibodies against SARS-CoV-2.

Turner and colleagues took up the challenge of identifying antibody-secreting memory plasma cells in the bone marrow of people who have recovered from COVID-19 (called convalescent individuals). Memory plasma cells are rare, and those specific for a particular disease-causing agent will obviously be extremely scarce. Nevertheless, Turner and colleagues detected memory plasma cells that secreted antibodies specific for the spike protein encoded by SARS-CoV-2 in 15 of 19 individuals, approximately 7 months after infection. Notably, when the authors obtained samples 4 months later (11 months after SARS-CoV-2 infection), the number of such plasma cells had remained stable in all but one of the individuals analysed. Those plasma cells did not proliferate, which classifies them as bona fide memory plasma cells. Their numbers equalled those of memory plasma cells found in the individuals after vaccination against tetanus or diphtheria, and which provide long-term immunity to those diseases.

When Turner et al. tracked the concentrations of antibodies against SARS-CoV-2 in the individuals’ blood serum for up to one year, they observed a biphasic pattern (Fig. 1). In the acute immune response around the time of initial infection, antibody concentrations were high. They subsequently declined, as expected, because most of the plasma cells of an acute immune response are short-lived. After a few months, the antibody concentrations levelled off and remained more or less constant at roughly 10–20% of the maximum concentration observed. This is consistent with the expectation that 10–20% of the plasma cells in an acute immune reaction become memory plasma cells5, and is a clear indication of a shift from antibody production by short-lived plasma cells to antibody production by memory plasma cells. This is not unexpected, given that immune memory to many viruses and vaccines is stable over decades, if not for a lifetime8.

Figure 1 | The immune response to SARS-CoV-2 infection. Data are becoming available that shed light on longer-term aspects of the human immune response to coronavirus infection. One component of the defence response is the production of antibodies that target viral proteins (red line). During the initial, acute phase of the immune response, antibody levels peak rapidly; this peak is generated by short-lived immune cells called plasma cells. Turner et al.1 present clinical evidence, from people who have had COVID-19, that long-lived, memory plasma cells that produce antibodies are generated in the bone marrow. These cells provide long-term antibody production that offers stable protection at a level of 10–20% of that during the acute phase (blue line). Memory plasma cells are a cell type that can be maintained for many years, if not a lifetime8. Wang et al.2 have characterized antibody responses at between six months and a year in people who have been infected with SARS-CoV-2; their results also provide evidence for the generation of immunological memory.

For SARS-CoV, a coronavirus very like SARS-CoV-2 that was originally identified in 2003 and causes severe acute respiratory syndrome (SARS), the continued presence of high concentrations of neutralizing antibodies in blood serum for more than 17 years was reported9 in 2020. Wang and colleagues’ results suggest that long-term immunity might also be expected for SARS-CoV-2. The authors report a follow-up investigation of serum antibodies and memory B cells specific for SARS-CoV-2 approximately one year after infection. The individuals studied had previously been analysed by Wang and colleagues’ group after six months10, but it is only now, after a year, that the transition from an acute immune reaction to the generation of immunological memory has become evident.

Wang et al. show that, between 6 and 12 months after infection, the concentration of neutralizing antibodies remains unchanged. That the acute immune reaction extends even beyond six months is suggested by the authors’ analysis of SARS-CoV-2-specific memory B cells in the blood of the convalescent individuals over the course of the year. These memory B cells continuously enhance the reactivity of their SARS-CoV-2-specific antibodies through a process known as somatic hypermutation. The authors demonstrated this with in vitro tests of antibody neutralization of a broad collection of SARS-CoV-2 variant strains.

Finally, Wang and colleagues show that immunity can be boosted even further in convalescent individuals by vaccinating them after a year. This resulted in the generation of more plasma cells, together with an increase in the level of SARS-CoV-2 antibodies that was up to 50 times greater than before vaccination. Some of the plasma cells will probably be recruited to become memory plasma cells, although this remains to be demonstrated formally, as does the induction of stable, long-term memory as a consequence of SARS-CoV-2 vaccination.

In evaluating vaccine efficacy, we should not expect the high antibody concentrations characteristic of acute immune reactions to be maintained in the memory phase11. It is an old misconception, when advocating frequent revaccinations, that antibody concentrations during the acute immune reaction can be compared with those later on, to calculate an imaginary ‘half-life’ of antibody-mediated immunity. This ignores the biphasic character of the immune response (Fig. 1).

The good news is that the evidence thus far predicts that infection with SARS-CoV-2 induces long-term immunity in most individuals. This provides a welcome positive note as we wait for further data on memory responses to vaccination.

doi: https://doi.org/10.1038/d41586-021-01557-z

https://www.nature.com/articles/d41586-021-01557-z