Affimed, NKMax: FDA OKs IND Application for Combo Therapy for Solid Tumors

 Affimed N.V. (NASDAQ: AFMD), a clinical-stage immuno-oncology company, and NKMax America Inc., a clinical stage biotech company, announced today that the U.S. Food and Drug Administration (FDA) cleared an investigational new drug application (IND) for an Affimed and NKMax America co-sponsored Phase 1/2a dose escalation and expansion study in which the two companies will investigate the combination of AFM24, an EGFR/CD16A innate cell engager (ICE®), and SNK-01, an autologous NK-cell product, in patients suffering from tumors known to express EGFR. The combination represents a novel approach to exploring innate immunity-based therapeutics to treat patients with solid tumors who failed conventional therapy with the aim to improve outcomes for high-medical need patient populations.

“This combination is part of our overall development strategy for AFM24, the first and only innate cell engager in clinical development for solid tumors. In addition to NK cell-based combinations, we are also developing AFM24 as single agent and in combination with atezolizumab in several tumor indications,” said Dr. Andreas Harstrick, Affimed’s Chief Medical Officer. “The mechanism of action of the two compounds could be highly synergistic as AFM24 has strong binding affinity to NK cells, directing them to kill tumor cells. Moreover, this combination approach represents an opportunity to supplement patients with dysregulated innate immune systems with targeted cellular therapy.”

https://finance.yahoo.com/news/affimed-nkmax-america-announce-fda-103000614.html

Achilles Therapeutics Prices IPO at $18

 Achilles Therapeutics plc (NASDAQ: ACHL), a clinical-stage biopharmaceutical company developing precision T cell therapies to treat solid tumors, today announced the pricing of its initial public offering in the United States of 9,750,000 American Depositary Shares (“ADSs”) representing 9,750,000 ordinary shares at an initial public offering price of $18.00 per ADS for total gross proceeds of $175.5 million. All ADSs sold in the offering are being offered by Achilles. The ADSs are expected to begin trading on The Nasdaq Global Select Market on March 31, 2021 under the ticker symbol “ACHL.”  In addition, Achilles has granted the underwriters a 30-day option to purchase up to an additional 1,462,500 ADSs at the initial public offering price, less underwriting discounts and commissions. The offering is expected to close on April 6, 2021, subject to customary closing conditions.

J.P. Morgan, BofA Securities and Piper Sandler are acting as joint book-running managers for the offering. Chardan, Oppenheimer & Co, and Kempen & Co are acting as co-managers.

http://www.globenewswire.com/news-release/2021/03/30/2202009/0/en/Achilles-Therapeutics-Announces-Pricing-of-Initial-Public-Offering.html

Pfizer: Covid vaccine 100% effective in ages 12 - 15

 Pfizer says its Covid-19 vaccine is safe and 100 percent effective in preventing the illness in teenagers ages 12 to 15.

"This is exactly the news that we hoped to hear," said Dr. Buddy Creech, a pediatric infectious disease expert at the Vanderbilt University Medical Center in Nashville, Tennessee. Creech was not involved in the Pfizer research.

The vaccine, given in two doses three weeks apart, is already cleared for emergency use in people ages 16 and up.

The company plans to request emergency use authorization for 12- to 15-year-olds in the coming weeks, "with the hope of starting to vaccinate this age group before the start of the next school year," Pfizer CEO Albert Bourla said in a statement.

"We share the urgency to expand the authorization of our vaccine to use in younger populations and are encouraged by the clinical trial data from adolescents between the ages of 12 and 15," Bourla said.

The findings, which were announced Wednesday in a news release, have not been peer-reviewed.

More than 2,200 young teenagers were enrolled in the Pfizer vaccine trial in the U.S. About half got the real shots, while the others got placebo shots. (The adult trial was much larger, with more than 43,000 participants.)

Pfizer said 18 cases of Covid-19 were reported among the teenagers who got the placebo, compared with none in those who got the real vaccine.

Side effects generally mirrored those in adults, such as a sore arm, fatigue and headache.

Uğur Şahin, CEO of Pfizer's German partner, BioNTech, said in the statement that the results were "encouraging given the trends we have seen in recent weeks regarding the spread of the B.1.1.7" variant of the coronavirus, which has been shown to be more transmissible.

What's more, teens in the trial who got the vaccine were later found to have levels of neutralizing antibodies — needed to wipe out the virus — similar to levels in older teens and young adults who had been vaccinated.

"Will it be 100 percent efficacious in the real world? Who's to say? But what we know is that when we move this vaccine down into teenagers, it behaves the exact same way that it does in adults, or even better," Creech said.

Pfizer's Phase 3 clinical trial in adults found that the vaccine was around 95 percent effective in preventing symptomatic illness. That ticked down slightly, to 90 percent, in real-world data released Monday by the Centers for Disease Control and Prevention.

Creech said he looks forward to seeing the full data from the trial.

"There may be subtle differences there that we really have to keep an eye on for children," he said. "If there are slightly higher rates of fever, or if there's slightly higher rates of muscle or joint aches, that has a different meaning in children than in adults."

Pfizer is also studying how well the vaccine works in children ages 6 months to 11 years old. The first doses in that trial were administered last week.

https://www.nbcnews.com/health/health-news/pfizer-says-its-covid-vaccine-100-percent-effective-young-teens-n1262550

Antibody evasion by the P.1 strain of SARS-CoV-2

 

• Wanwisa Dejnirattisai #
• Daming Zhou #
• Piyada Supasa #
• Jingshan Ren
• David I. Stuart
• Gavin R. Screaton

DOI:https://doi.org/10.1016/j.cell.2021.03.055

PDF: https://www.cell.com/action/showPdf?pii=S0092-8674%2821%2900428-1

Highlights

• 1
  Despite similar RBD mutations P.1 is easier to neutralize than B.1.351.
• 2
  P.1, B.1.351 and B.1.1.7 partially or fully escape most VH3-53 antibodies.
• 3
  mAb 222 (VH3-53) retains neutralisation against all 3 variants.
• 4
  Neutralisation is restored in VH3-53 chimeric antibodies with mAb 222 LC.

Summary

Terminating the SARS-CoV-2 pandemic relies upon pan-global vaccination. Current vaccines elicit neutralizing antibody responses to the virus spike derived from early isolates. However, new strains have emerged with multiple mutations: P.1 from Brazil, B.1.351 from South Africa and B.1.1.7 from the UK (12, 10 and 9 changes in the spike respectively). All have mutations in the ACE2 binding site with P.1 and B.1.351 having a virtually identical triplet: E484K, K417N/T and N501Y, which we show confer similar increased affinity for ACE2. We show that, surprisingly, P.1 is significantly less resistant to naturally acquired or vaccine induced antibody responses than B.1.351 suggesting that changes outside the RBD impact neutralisation. Monoclonal antibody 222 neutralises all three variants despite interacting with two of the ACE2 binding site mutations, we explain this through structural analysis and use the 222 light chain to largely restore neutralization potency to a major class of public antibodies.

https://www.cell.com/cell/fulltext/S0092-8674(21)00428-1

Tokyo airport trials CommonPass digital health passport

 All Nippon Airways (ANA) has begun a trial of its CommonPass app showing a traveller’s COVID-19 status at Tokyo’s Haneda Airport.

It’s part of efforts by the global travel industry to make cross-border travel easier and safer and is one of several digital health passports being trialled around the world.

The idea is to provide an accurate but fast way of ensuring passengers are safe to travel and prevent the spread of COVID-19 and potential variants.

Backed by the World Economic Forum, the app is one of a number of digital health passports being developed and certifies both coronavirus test results and vaccination status.

ANA officials began using the system to check passengers’ smartphones, which confirmed negative virus test results at a check-in counter, Kyodo News reported.

Ikuko Osato, a 44-year-old nurse from Fukushima Prefecture who participated in the test run as a volunteer, told the website: “As the process went smoothly, I had more time and energy to spare.”

Juichi Hirasawa, ANA senior vice president for corporate planning, said: “We are constantly looking for ways to make the travel experience safer and more convenient.

“Our trials of the CommonPass Health application will help us to ensure that these procedures will enable us to simplify international travel while also protecting passenger privacy,”

The UK began trialling Common Pass late last year, beginning in October when a small number of passengers began using the system.

The digital pass was created by the Commons Project, which received startup funding by the Rockefeller Foundation two years ago.

It involves a QR code that can be scanned by airlines staff and border officials to show that the traveller’s last test was negative.

There are other initiatives to use digital technology to prevent the spread of coronavirus through air travel: Switzerland’s ender diagnostics is working with Swiss International Airlines, a subsidiary of Lufthansa, on a system providing rapid molecular tests for cabin crew.

https://pharmaphorum.com/news/tokyo-airport-begins-trial-of-digital-health-passport/

India extends shelf life of AstraZeneca vaccine

 India's drug regulator has allowed the AstraZeneca Covid-19 vaccine to be used for up to nine months from its manufacture date, as opposed to the prescribed six months, according to a document reviewed by Reuters and a source.

The approval, given to a licensed version of the drug made by the Serum Institute of India (SII) and exported to dozens of countries, could help health authorities minimise vaccine wastage and better plan their inoculation programmes.

Some African countries have only until the middle of next month to use up more than a million doses of the vaccine - branded Covishield by SII - if the shelf life is not extended.
"You are permitted to apply the shelf-life of 9 month to unlabelled vials available on hand," India's drugs controller-general, VG Somani, wrote late last month in reply to a request from the SII.

AstraZeneca said in a statement last week that its product could be stored, transported and handled at normal refrigerated conditions for at least six months. The World Health Organization website also gives the shelf-life of Covishield and the South Korean-made AstraZeneca shot as six months.
Reuters has reviewed Somani's approval, which has been communicated to some African countries, but could not determine if his recommendation applied to unused vials. Each vial typically contains 5 millilitre of vaccine, or 10 doses.
The source, with direct knowledge of the matter but not authorised to discuss it publicly, said the approval was given based on data submitted by the SII. The source did not specify what kind of data was shared by the company, the world's biggest vaccine maker.
Somani, the SII and AstraZeneca did not immediately respond to requests for comment.
India has so far administered 55 million Covishield doses at home and exported nearly 64 million. India is also using another vaccine developed domestically by Bharat Biotech.

https://timesofindia.indiatimes.com/india/india-extends-shelf-life-of-astrazeneca-vaccine-report/articleshow/81760610.cms

Can We Mix and Match COVID-19 Vaccines? Not Yet

 

• The United Kingdom’s National Health Service (NHS) is conducting research to discover the effectiveness of combining two different vaccines.
• The purpose of this 13-month trial is to see how well people’s immune systems respond once they’re “primed” with one type of vaccine and then boosted with another.
• Experts say at this point it’s still just a trial, and it’s not clear it will be helpful.

Even as COVID-19 vaccinations increase across the globe, experts have wondered whether it’s possible to get people vaccinated more quickly if vaccines can be mixed and matched.

Evidence of vaccine supply chain issues show that potentially allowing people to use different vaccines may help people get fully vaccinated more quickly.

In an attempt to create more flexible COVID-19 vaccination programs, the United Kingdom’s National Health Service (NHS) is conducting research to discover the effectiveness of combining two different vaccines.

It’s called the Com-COV study, and it’s raising important questions, like whether this can increase or decrease vaccine effectiveness.

“By using two different vaccines, there is not going to be a greater magnitude of protection against the disease,” Dr. Nikhil Bhayani, infectious disease specialist with Texas Health Resources, told Healthline.

However, Bhayani emphasized that at this time, “[the] use of two different vaccines is not recommended.”

Bhayani also cautioned that while the Pfizer-BioNTech, Moderna, and Johnson & Johnson vaccines do offer a degree of protection against COVID-19, “as we see more variant strains the expectation of the vaccine protecting you from the disease could decrease. However, clinical trials will be warranted to prove this.”

How does the Com-COV trial work?

According to the NHS, the purpose of this 13-month trial is to see how well people’s immune systems respond once they’re “primed” with one type of vaccine and then boosted with another.

Researchers want to see how strong the immune system response is when the second dose is separated from the first dose by different amounts of time.

Researchers will also use blood samples from trial volunteers to monitor the effect of different dosing regimens on participants’ immune system responses, and look for any additional adverse reactions to these combinations of vaccines.

The two vaccines used for this study are from AstraZeneca and Pfizer-BioNTech.

However, the NHS added that “if more vaccines are approved for use in the U.K. after this study starts, they may be added to the trial.”

It’s important to note, according to the most current guidelines from the Centers for Disease Control and Prevention (CDC)Trusted Source, that a lack of available safety data means COVID-19 vaccines shouldn’t be mixed unless there’s an exceptional situation, like a shortage of the vaccine the person first received.

Not first time vax mixing attempted

“We use this approach to protect against pneumococcal disease, which is serious illness caused by Streptococcus pneumoniae bacteria and can include pneumonia, bloodstream infection, meningitis, among other infections,” said Dr. Dana Mazo, hospital epidemiologist and assistant professor of medicine at Mount Sinai Hospital in New York.

She explained that in some instances, one type of vaccine can increase the effectiveness of another.

“There are two different types of pneumococcal vaccines that have different mechanisms of action, and in certain situations we recommend boosting one with the other,” she said.

According to Bhayani, scientific data has shown that getting several vaccines at the same time does not cause any chronic health problems.

When every new vaccine is licensed, “it has been tested along with the vaccines already recommended,” he added.

AstraZeneca, Pfizer-BioNTech vaccines work differently 

Mazo said the AstraZeneca and Pfizer-BioNTech vaccines use two different technologies to protect against COVID-19.

The Pfizer-BioNTech vaccine is an mRNA vaccine, but AstraZeneca’s vaccine is not.

“AstraZeneca uses adenovirus vector technology, similar to Johnson & Johnson,” Mazo explained. “[But] both vaccines contain instructions that tell our cells to make the spike protein of the SARS-CoV-2 virus that causes COVID-19.”

Mazo said this causes our bodies to then build an immune response against the coronavirus spike protein that helps protect us if we’re exposed to the virus.

She pointed out that the difference is how the two vaccines transport these instructions to our cells.

“Pfizer uses mRNA coated in lipid (fatty) material to get the information into the cells,” she said, “while AstraZeneca uses a weakened version of an adenovirus, a common cold virus, to do the same thing. Both vaccines currently require two doses.”

According to Bhayani, the altered virus in AstraZeneca’s vaccine can’t make you sick, but it carries a gene from the coronavirus’s spike protein, the portion of the virus that triggers an immune response.

“As a result, the immune system manufactures antibodies that work against COVID-19, teaching the body how to respond should one become infected,” he said.

Efficacy of combined approach unknown; trial offers valuable data

“It is a new approach, which is why the U.K. is proposing to do a research study to evaluate it,” Mazo said.

She explained it’s possible that getting the information to the cells in two different ways (one via mRNA and one by adenovirus viral vector) could create a better response either in terms of stronger or longer protection.

But this approach could also compromise overall effectiveness.

“This question about whether it will be better or worse is why this approach is most appropriate in the context of a study,” Mazo said. “Since we do not know the answers, we want to learn from it.”

Mixing vaccines ‘not yet ready for prime time’

Without question, there are critical COVID-19 vaccine shortagesTrusted Source.

How we resolve these issues to protect the majority of people from the pandemic and return to a more normal situation is a serious concern.

But is mixing different vaccines better than not receiving a needed second dose?

“Ideally you want to give the second dose to achieve the 90 percent efficacy,” Bhayani said.

“However, in dire circumstances, if there is a shortage of COVID vaccines, it would be better to get more people vaccinated with a single dose. At least some protection is better than none.”

Dr. Eric Cioe-Peña, director of global health at Northwell Health in New York, believes that at this time, there’s simply too little known about mixing vaccines.

“We don’t know if there’s an advantage to mixing vaccines or a disadvantage. Further study is needed of the effects of mixing. It’s not yet ready for prime time,” he said.

The bottom line

U.K. researchers are conducting a clinical trial to learn whether mixing the Pfizer-BioNTech and AstraZeneca vaccines can help increase the number of people who can be vaccinated with the needed two doses to protect against COVID-19.

Experts say there’s not enough data to know whether this approach is an effective solution, and it might even reduce the protection offered by these vaccines.

The CDC currently recommends against mixing vaccines except under exceptional circumstances.

According to experts, in situations when it’s either mix different COVID-19 vaccines or not receive the second dose, it’s better to use the same vaccine in one dose until we know more.

https://www.healthline.com/health-news/can-we-mix-and-match-covid-19-vaccines-experts-say-not-yet#The-bottom-line