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INO-4800. June 2022: Order from China and LMICs (Low Mid-Income Countries) for Advaccine pGx9501 booster, C2K Device. Ino earns some regulatory, commercialization milestones, $206M total. Royalty equals a high single-digit percentage of annual net sales. Grease the skid for HK IPO.
VGX-3100
2H22: Apollo Bio Interim Readout. Ino earns some milestone, $20M total
12/14/21: The first participant has been dosed in the Phase 3 trial of VGX-3100 for cervical HSIL in China. This trial is being run by ApolloBio and is similar in design to REVEAL2. The trial is expected to enroll up to 84 participants.
In addition to the upfront payment that we received in 2018, we are entitled to receive up to an aggregate of $20M upon the achievement of specified milestones related to the regulatory approval of VGX-3100. We will be entitled to receive royalty payments based on a tiered percentage of annual net sales, with such percentage being in the low- to mid-teens.
What is important are Pre-orders. Upon good STV Iterim Readout which meets or exceeds Primary Endpoint of 50% confirmed cases, even before WHO granting EUL, Ino can start talking to LMICs for Pre-orders. pGx9501 booster EUA may trigger large orders in China and from Chinese government for Vaccine Diplomacy.
• Booster market is much larger than primary vaccine market
• Inactivated and viral vector vaccines have been administered primarily in Low- and Middle- Income countries
• About 2.4 billion doses of the Chinese vaccines have been administered in China, but almost 1 billion doses have gone to 110 other countries
• Global demand for heterologous boosters cannot be met with currently licensed (EUA or full authorization) for primary series or those not currently licensed but with Phase 3 data efficacy data
• Market reset focused now on heterologous boost
3/15/22 8AM ET INOVIO to Present at Oppenheimer's 32nd Annual Healthcare Conference
PLYMOUTH MEETING, Pa., March 8, 2022 /PRNewswire/ -- INOVIO (NASDAQ:INO), a biotechnology company focused on developing and commercializing DNA medicines to help protect people from infectious diseases and help treat people with cancer and HPV-associated diseases, today announced that Dr. J. Joseph Kim, President and CEO, will participate in a fireside chat and 1x1 investor meetings at Oppenheimer's 32nd Annual Healthcare Conference on Tuesday, March 15, 2022.
Oppenheimer's 32nd Annual Healthcare Conference
Date: Tuesday, March 15, 2022
Time: 8:00 AM ET
Presentation Format: Fireside Chat
A webcast of the presentation will be available through the INOVIO Investor Relations Events page at https://ir.inovio.com/events-and-presentations/default.aspx The presentation time is subject to change.
INO-4800
? April 2022: Advaccine heterologous and homologous boost P2 trials Interim Readouts. Apply for EUA. WHO STV Interim Readout. Apply for EUL. COVAX Pre-orders.
? 3Q22: INNOVATE Interim Readout. Primary Endpoint: Severe Disease. Apply for EUAs in Philippines ????, Colombia ????, Brazil ????, Mexico ????
VGX-3100
? 2Q22: Start A(nal)IN, V(ulvar)IN P3’s. Receive ODD’s for both. Apply for Breakthrough Therapy Designation.
? 4Q22: Report REVEAL2 efficacy data and safety follow-up through week 40
INO-3107
? 2H22: P1/2 immune responses and early clinical benefit data. Apply for Breakthrough Therapy Designation, eligible for PRVs, can be sold to other BPs for
$100M-$350M
INO-5401
? 2Q22: Present additional overall survival OS36 data including median OS for MGMT-methylated cohort
Platform Development
? 1H22: Report INO-4500 Lassa P1b data
? 2H22: Report INO-4201 Ebola P1b booster data
? 2H22: Initiate COVID-19 dMAb trial
? 2H22: Report INO-4700 MERS P2 data
3/7/22 Omicron Wave Was Far Deadlier For the Vaccinated Elderly In CA Than Delta [JK was right in changing Primary Endpoint to severe disease]
As the U.S. death toll from the pandemic nears one million people and the worldwide death toll hits six million, new data suggests that the recent Omicron wave was much deadlier for the elderly, whether they were vaccinated or not, than previously understood.
We know that Omicron snuck past most people's natural and vaccine-given immunity, creating a wave of confirmed cases in the U.S. in December and January that was exponentially higher than any we've previously seen in the COVID pandemic. And this larger number of cases, even if the majority of them were mild, did lead to a spike in deaths in the past three months even in the highly vaccinated Bay Area — over 10% more deaths per week than during the earlier Delta wave.
But many of those deaths occurred in patients who were vaccinated and boosted, as Bay Area News Group reports this week, further confirming that while the vaccines may be highly effective, they are not as effective for everyone. And it confirms that you still don't want Omicron, and you definitely don't want to risk spreading it to elderly parents and grandparents despite their vaccine status.
In California, in the Omicron wave alone, 436 patients have died to date despite being fully vaccinated and boosted, and over 1,300 people died despite having two vaccine doses. That's compared to 3,000 deaths during this wave among the unvaccinated in California — and 2,900 among the unvaccinated in the Delta wave.
Compared to the Delta wave, Omicron led to more serious outcomes for the vaccinated — only 533 people who were fully vaccinated died during the Delta wave in California.
"We’ve seen some chinks in the armor of vaccines that we didn’t see before," says Santa Cruz County Deputy Health Officer Dr. David Ghilarducci, speaking to Bay Area News Group. "As good as the vaccines are, they’re not 100% protection."
We can see this in microcosm with 10 deaths that occurred in Santa Cruz County during a three-week period in the Omicron surge. Of those deaths, nine occurred in patients who had at least two vaccine doses, and five of those patients had been boosted.
But, all nine patients were 70 or older, and most had underlying health conditions. According to the county's data, one patient was in his early 100s, three were in their 90s, two were in their 80s, and the remaining three were in their 70s. Throughout the pandemic, it has been the elderly, and especially those with specific health problems, who have had the worst outcomes from COVID infection, and despite creating milder infections for many, the Omicron variant was no different.
Looking forward to brighter days with much less infection and death, infectious disease experts at UCSF tell the Chronicle this week that it's not an inevitability that the 60+ percent of Americans who have not yet had COVID-19 will definitely get some version of it this year or next.
"From my perspective, no, it’s not inevitable," says Dr. Bob Wachter, Chair of Medicine at UCSF and a frequent voice of optimism and pragmatism over the last two years. Wachter cites the decreasing presence of the virus in the Bay Area in particularly, which is going to lead to far fewer chances for people to get exposed in the coming months.
Certainly more variants and winter surges could be on their way, but we should not throw in the towel and go expose ourselves on purpose, says Dr. Peter Chin-Hong, an infectious disease specialist.
"Are we all going to get it? Yes, biologically, that might happen,” Chin-Hong tells the Chronicle. "Are we at a time to embrace that philosophy? No, because the virus is still causing a lot of suffering. Almost 2,000 deaths per day [nationally] is no walk in the park."
In the last seven days alone, the Bay Area has seen an additional 151 deaths — and we should remember that such a significant and swift death toll was hard to fathom in the early days of the pandemic. In May 2020, it took over a month for the region to rack up 150 deaths, despite no one being vaccinated. And even as most businesses were back open last fall, toward the end of the Delta wave, it took about three weeks for the Bay Area to tally that many COVID deaths.
The $155.0 million increase in research and development expenses for the year ended December 31, 2021 as compared to 2020 was primarily due to increases of:
•$39.5 million in drug manufacturing, outside services and clinical study expenses related to INO-4800;
•$35.0 million in expenses related to manufacturing capacity access fees;
•$21.9 million related to the acquisition and installation of manufacturing equipment related to INO-4800;
•$13.6 million in engineering services and expensed equipment and inventory related to our CELLECTRA® 3PSP device array automation project;
•$12.8 million in expensed materials purchased in preparation for the manufacturing of INO-4800; and
•$12.1 million in employee and contractor compensation.
These increases were primarily offset by an increase in contra-research and development expense recorded from grant agreements of $6.2 million, among other variances.
Contributions received from current grant agreements and recorded as
contra-research and development expense were $53.7 million and $47.5 million for
the years ended December 31, 2021 and 2020, respectively. The increase year over
year was primarily due to increases of $5.9 million, $3.6 million and $2.4
million earned from the DoD OTA Agreement, CEPI Lassa and MERS grant and
reimbursements from Advaccine, respectively, partially offset by decreases of
$3.2 million and $3.2 million, earned from CEPI and Gates, respectively, related
to INO-4800 and device development activities, among other variances.
3/4/22 Dr. Robert Malone to CDC chief: 'Time to show us the data'
Reacts to Walensky's remarkable admissions regarding COVID response
CDC Director Dr. Rochelle Walensky's admissions regarding her agency's COVID-19 response are welcome – affirming the concerns of many censored and maligned health scientists over the past two years – but they are not enough, said Dr. Robert Malone in a video interview Friday with WND.
"I'm to the point now where I have no faith in these kinds of words. I want to be shown the information," said Malone, the key inventor of the mRNA technology platform that later was used in the Pfizer-BioNTech and Moderna vaccines.
"I think it's now time to show us the data. That is the only thing that matters now."
https://www.wnd.com/2022/03/dr-robert-malone-cdc-chief-time-show-us-data/
"I think it's now time to show us the data. That is the only thing that matters now."
As WND reported Friday, Walensky admitted in remarks Thursday night at the Washington University Medical School in St. Louis that the CDC exercised "too little caution and too much optimism" about the effectiveness of the vaccines; had a sophisticated COVID data system (while, as the New York Times reported, the agency withheld data from the public); gave the public the impression science is "foolproof"; and didn't balance the risk of COVID-19 with the unintended consequences of mitigation efforts, such as opioid deaths and "mental health challenges."
Malone – who has been banned from Twitter and LinkedIn for making and referencing factual statements and science-based observations about the pandemic – said it was "very kind" of Walensky to admit she was too optimistic about the vaccines, but "it would have been more useful if she had done it in real time."
Regarding "the data," Malone said "we're past the point of assuming good intent on the part of the CDC."
"I think they have spent that currency, and we now just need to see the data and stop playing word games," he said.
In December, President Biden clearly had Malone and other medical scientists in mind when he angrily charged that the "vaccine hesitancy" of an estimated 40 million Americans had been "fueled by dangerous misinformation".
'The depth and consequences of their actions'
Walensky's admission that she and her agency mischaracterized "science" is significant, Malone said, but she "still is not going all the way to acknowledging that the government is not the sole arbiter of truth and that she is not the bastion of truth."
"We're not hearing any language to the effect that we (the CDC) should have more actively engaged in the broader community, that we should have been more modest, that we should have sought the counsel of docs who were actively practicing and treating COVID patients," he said.
"We're not seeing anything that indicates remorse, humility or a recognition that there needs to be a major change in the CDC and Department of Health and Human Services."
Malone said Walensky also is "taking no ownership of the rather overt advocacy on behalf of the pharmaceutical and vaccine industry."
"These comments strike me as a little coy," he said. "I don't see evidence of a bureaucrat who has come to terms with the depth and consequences of their actions over the last two years."
Malone said the "reputation of the CDC has been destroyed under her watch."
Walensky, he said, basically has "overseen the weaponization of the CDC to serve a political agenda during the course of this outbreak."
"This is not something that can be excused. There must be accountability."
Biden 'still dug in'
Malone is taking a cautious view of the lifting of mandates by Democratic governors, noting that in Europe skeptics of the European Union's easing of COVID restrictions are warning it may be a temporary reprieve. The Eurosceptics argue there is legislation underway to make vaccine requirements permanent.
He said that he and many of his colleagues are "very, very wary of the government and government messaging and believe that we can trust nothing until it's been verified."
President Biden, he noted, is still "dug in on insisting that we have a current medical emergency and that that justifies the invocation of the emergency powers," which was renewed a week ago.
"It's nice to hear the pretty words from Dr. Walensky," he said. "But I am tired of pretty words. I want to see actions."
Maxim Group analyst Jason McCarthy, Ph.D., buy Ino, PT to $11 from $20, 2/2/22
In an industry wide series of research reports, Jason lowered price targets on stocks in his coverage universe, saying industry multiples have contracted but company outlooks remain positive.
“Following a strong 2020 with CV impacting a number of sectors and driving an inflow of capital into biotech (record numbers of IPOs, SPAC mergers, and venture capital deals), 2021 started a sell-off in the industry which has only accelerated into 2022 with indices 25% to 50% off 2021 highs.
While fundamentals remain unchanged and balance sheets for some have been strengthened considerably, this must be balanced with shifting macro fundamentals around areas like rising interest rates.”
However, he said pre-revenue biotech is a data/event driven space and thus execution on clinical programs and reaching key catalysts with positive outcomes will be critical to support valuations rebounding.
By t_babur, 10-K, pg 67: We have entered into agreements with contract manufacturers for INO-4800 that contain minimum purchase requirements by us in 2022.
Manufacturing commitments $47,427,000
Payments Due by Period, Less than 1 year: $47,427,000
Medigen and 4800 being admin’ed concurrently.
Trial entry, randomization: Once electronic data collection has been completed the volunteer automatically enters the trial and a random allocation of their trial vaccine is generated (by an algorithm that ensures eventual balance in the characteristics just recorded between each study vaccines and its placebos) and displayed. The volunteers will be randomly allocated either to placebo or to one of the study vaccines.
Follow-up: Each participant will be contacted weekly for 52 weeks for information as to whether any potentially relevant symptoms have arisen, with laboratory testing triggered if the report suggests COVID-19.
Adaptive design: A global Data Monitoring Committee will keep the accumulating safety results and major outcome results under regular review. Different candidate vaccines may be available or suitable to enter the trial at different times; for each candidate vaccine, the primary efficacy results are expected within 3-6 months of the vaccine entering the trial. By using a shared placebo/control group and a common Core protocol to evaluate multiple candidate vaccines in the trial, resources allocated to the evaluation of each candidate vaccine are judiciously saved while a high standard of scientific rigor and efficiency is ensured.
ISRCTN15779782
https://doi.org/10.1186/ISRCTN15779782
Homologous and Heterologous boost trials Data out 2Q22 for Advaccine IPO. 3/1/22
“I believe Advaccine is planning to go IPO this year. However, that will most likely depend on clinical progress as well as market condition.” 2/8/22
Hartaj Singh: you’re in vitro data matches up pretty well against some of the commercial and vaccines in approval. Just quick question on WHO trial, are they planning on doing any protocol amendments there to also kind of for the Omicron and maybe future variants, just any updates there?
Dr. Joseph Kim
what I can tell you is Omicron has equally impacted all vaccines being developed and trials currently undergoing. So, as you know, STV is run and sponsored by the WHO and. And they have the full control. And we have full confidence that they will be able to execute the trial as they see most appropriately. So far, everything is moving as they had stated in the fall.
Reply to Roger Song of Jefferies:
The vaccine homologous and heterologous boost trials, that’s fully enrolled. They expect to have the data in the second quarter of this year. So, it’s of course being run and executed by our partner in China, Advaccine. So, we expect the data from that trial sometime in the next quarter.
In terms of additional heterologous boost, we’re deeply investigating the feasibility and execution ability of a heterologous boost trial, again outside the U.S. where we can compare with two other most prolifically utilized primary vaccine for COVID in viral vector and inactivated vaccines. So, we’re in the planning and feasibility stage. But, if this is a go, we think we can execute this all through 2022.
3/6/22 “According to the STV team, the Philippines has already reached the primary outcome of the trial wherein 133 participants tested positive for Covid-19 after completing the two-dose schedule of the first study vaccine,”
According to DOST, the Philippines, Mali, and Colombia have reached the target number of primary endpoints and are currently validating and analyzing the initial data while awaiting instructions from the WHO regarding the administration of the second study vaccine.
7,083 participants of WHO solidarity trials get first dose of Covid-19 jabs
A total of 7,083 participants of the World Health Organization (WHO) Solidarity Trials Vaccines (STV) in the country have already received their first dose jabs of coronavirus disease (Covid-19), the Department of Science and Technology (DOST) reported.
In a taped report, DOST Secretary Fortunato “Boy” de la Pena said that as of Feb. 21, at least 6,417 participants have completed the two-dose schedule of the vaccine.
The Solidarity Trials for Vaccines was organized by the WHO and recruited its first volunteer on Sept. 30.
De la Pena added that eight hospitals and two community-based sites have already conducted the recruitment activities.
Included in the list of trial sites were Philippine General Hospital, Lung Center of the Philippines, Makati Medical Center, Quirino Memorial Center, St. Luke’s Medical Center, Medical Center Manila, Baguio General Hospital, and San Juan De Dios Hospital, as well as two community-based centers in Sampaloc, Manila and Crame Quezon City.
https://mb.com.ph/2022/03/06/7083-participants-of-who-solidarity-trials-get-first-dose-of-covid-19-jabs/
2/15/22 As of Dec. 22, 2021, over 11,500 people had registered to take part in the project, WHO data showed.
Unblinding of the clinical trial could take place as early as the end of March and would determine whether the WHO recommends the Medigen vaccine for use against COVID-19.
https://focustaiwan.tw/society/202202150024
DOST Undersecretary for Research and Development Dr. Rowena Cristina L. Guevara said as of Jan. 3, a total of 5,901 participants have been inoculated with the first dose of COVID-19 vaccine, while 3,840 participants have completed their two-dose regimen.
“As of January 3, 2022, eight hospitals and two community-based sites have already conducted the recruitment activities with a total of 5,901 have already been vaccinated with first dose and 3,840 participants have already completed the two-dose schedule of the first study vaccine,” she told the Manila Bulletin in an interview.
The lead investigators of the trial are Dr. Jodor A. Lim and Dr. Marissa M. Alejandria of the University of the Philippines (UP) Manila-Philippine General Hospital (PGH).
Guevara explained that the WHO-coordinated global study “Solidarity Trial Vaccines” is implemented locally through the project “Solidarity Vaccine Trial in the Philippines: Randomized Trial of Candidate Vaccines for COVID-19”.
She said recruitment of participants are ongoing on the following sites:
Philippine General Hospital (PGH)
Lung Center of the Philippines (LCP)
Makati Medical Center (MMC)
Quirino Memorial Medical Center (QMMC)
St. Luke’s Medical Center (SLCM)
Medical Center Manila (MCM)
Baguio General Hospital
San Juan De Dios Hospital (SJDH)
Sampaloc, Manila (community-based)
Crame, Quezon City (community-based)
The project team is eyeing to enroll 15,000 to 20,000 Filipinos aged 16 and above to participate in the trial.
The enrolment of participants for the WHO STV started on Sept. 30, 2021.
Guevara said the study “will continue to run until the second quarter of 2022.”
https://mb.com.ph/2022/01/07/5901-participants-of-who-solidarity-trial-already-received-first-dose-of-covid-19-vaccines-dost/
Q4 2022 Earnings Forecast for Inovio Pharmaceuticals, Inc. Issued By Oppenheimer
Friday, March 4th, 2022
Inovio Pharmaceuticals, Inc. (NASDAQ:INO - Get Rating) - Stock analysts at Oppenheimer issued their Q4 2022 earnings estimates for Inovio Pharmaceuticals in a research report issued on Wednesday, March 2nd. Oppenheimer analyst H. Singh forecasts that the biopharmaceutical company will post earnings of ($0.29) per share for the quarter. Inovio Pharmaceuticals (NASDAQ:INO - Get Rating) last posted its earnings results on Tuesday, March 1st. The biopharmaceutical company reported ($0.50) earnings per share for the quarter, missing the Thomson Reuters' consensus estimate of ($0.32) by ($0.18). Inovio Pharmaceuticals had a negative net margin of 3,391.88% and a negative return on equity of 44.10%. The business had revenue of $0.84 million for the quarter, compared to analyst estimates of $0.55 million. During the same quarter in the previous year, the firm posted ($0.14) EPS. The business's revenue was down 85.0% compared to the same quarter last year.
Several other research firms also recently issued reports on INO. Zacks Investment Research raised shares of Inovio Pharmaceuticals from a "hold" rating to a "buy" rating and set a $5.50 price target on the stock in a research note on Wednesday, January 12th. Royal Bank of Canada reduced their target price on shares of Inovio Pharmaceuticals from $6.00 to $5.00 and set a "sector perform" rating for the company in a research note on Wednesday. Jefferies Financial Group reduced their target price on shares of Inovio Pharmaceuticals from $8.00 to $6.00 and set a "hold" rating for the company in a research note on Thursday, December 30th. StockNews.com raised shares of Inovio Pharmaceuticals to a "sell" rating in a research note on Tuesday. Finally, Bank of America raised shares of Inovio Pharmaceuticals from an "underperform" rating to a "neutral" rating and boosted their target price for the company from $8.00 to $10.00 in a research note on Friday, January 21st. They noted that the move was a valuation call. One equities research analyst has rated the stock with a sell rating, five have assigned a hold rating and two have assigned a buy rating to the company's stock. Based on data from MarketBeat.com, the stock has a consensus rating of "Hold" and a consensus price target of $11.25.
Inovio Pharmaceuticals stock opened at $3.11 on Friday. Inovio Pharmaceuticals has a 12-month low of $2.76 and a 12-month high of $10.81. The company has a market capitalization of $654.30 million, a price-to-earnings ratio of -2.85 and a beta of 0.65. The company has a debt-to-equity ratio of 0.03, a current ratio of 9.49 and a quick ratio of 9.49. The firm's fifty day moving average price is $4.08 and its 200 day moving average price is $6.16.
Large investors have recently modified their holdings of the company. BlackRock Inc. lifted its stake in Inovio Pharmaceuticals by 1.1% during the third quarter. BlackRock Inc. now owns 18,369,653 shares of the biopharmaceutical company's stock valued at $131,528,000 after purchasing an additional 197,952 shares during the last quarter. State Street Corp lifted its stake in Inovio Pharmaceuticals by 21.5% during the fourth quarter. State Street Corp now owns 13,300,430 shares of the biopharmaceutical company's stock valued at $66,369,000 after purchasing an additional 2,353,164 shares during the last quarter. Wasatch Advisors Inc. raised its holdings in shares of Inovio Pharmaceuticals by 37.3% during the fourth quarter. Wasatch Advisors Inc. now owns 4,926,125 shares of the biopharmaceutical company's stock valued at $24,581,000 after acquiring an additional 1,338,489 shares during the period. Geode Capital Management LLC raised its holdings in shares of Inovio Pharmaceuticals by 10.6% during the fourth quarter. Geode Capital Management LLC now owns 3,674,626 shares of the biopharmaceutical company's stock valued at $18,336,000 after acquiring an additional 351,457 shares during the period. Finally, Nuveen Asset Management LLC raised its holdings in shares of Inovio Pharmaceuticals by 22.5% during the second quarter. Nuveen Asset Management LLC now owns 2,162,309 shares of the biopharmaceutical company's stock valued at $20,045,000 after acquiring an additional 396,637 shares during the period. 36.28% of the stock is owned by institutional investors.
Has the Covid Opportunity Been and Gone for Inovio? Oppenheimer Weighs In
Mar 04, 2022, 03:27 PM
Every walk of life has its winners and losers, and this is no different in the land of coronavirus stocks. The term will forever be associated with the pandemic’s peak crisis when several companies set off on being the one to fend off Covid-19. Since the race began in early 2020, several have crossed the finish line and have been raking in the cash (Pfizer (PFE), Moderna (MRNA)) while others such as Novavax (NVAX) still appear poised to catch the gravy train just in time.
For Inovio Pharmaceuticals (INO), however, the prospects of Covid success appear dimmer than ever. The biotech company provided its quarterly business update early this week and the results were weak, which was bad enough. More importantly, investors’ focus naturally turned to the progress of INO-4800 – the company’s DNA Covid-19 vaccine candidate. Or lack of progress, that is. The program has been beset by numerous issues, and now the Phase 3 development (the INNOVATE trial) is being paused, as the company has decided to amend the clinical trial protocol.
The primary endpoint of the trial will be changed “from prevention of virologically confirmed COVID-19 disease to prevention of severe disease due to COVID-19.” Essentially, the vaccine has shown it is not as effective against the Omicron variant as the already available vaccines.
Investors did not like this development, as noted by Oppenheimer’s Hartaj Singh, who says there was “clear disappointment among investors regarding the delay of the INO-4800 COVID-19 vaccine.”
However, while Singh anticipates the commercialization of INO-4800 will be pushed out to 2023E (outside the US), the analyst keeps a positive stance.
“We note that this endpoint is already a secondary endpoint in the ongoing phase 3 and that INO is being prudent in amending the INNOVATE trial, in light of the declining vaccine efficacy (VE) among COVID-19 vaccines due to increasing COVID-19 variants,” the analyst said. “In addition, important pipeline projects such as VGX-3100 (cervical HSIL), INO-3107 (RRP) and INO-5401 (GBM) are moving forward with important catalysts in 2022. We stay bullish.”
Singh is indeed “bullish.” Backing his Outperform (i.e., Buy) rating is a $30 price target (reduced from $35), which suggests shares will still rise by ~865% over the coming year. (To watch Singh’s track record, https://www.tipranks.com/experts/analysts/hartaj-singh)
Most analysts aren’t quite so optimistic. The consensus view is that this stock is a Moderate Buy, based on 5 Holds and 2 Buys. That said, the average price target remains a bullish one; at $10.83, the figure still implies shares will surge ~248% in the year ahead. (See Inovio stock forecast on TipRanks https://www.tipranks.com/stocks/ino/forecast)
https://www.tipranks.com/news/article/has-the-covid-opportunity-been-and-gone-for-inovio-oppenheimer-weighs-in/
INO PT Lowered-to-$30 at Oppenheimer-while-maintaining-a-Buy-rating
March 2, 2022 12:56 PM EST
Oppenheimer analyst Hartaj Singh lowered the price target on Inovio Pharmaceuticals (NASDAQ: INO) to $30.00 (from $35.00) while maintaining a Buy rating …
https://www.streetinsider.com/Analyst+Comments/Inovio+Pharmaceuticals+%28INO%29+PT+Lowered+to+%2430+at+Oppenheimer/19713632.html?classic=1
2Q-4Q22 Catalysts
INO-4800
? April: heterologous and homologous boost P2 trials Interim Readouts in China with Advaccine.
Apply for EUA
? April: the WHO STV Interim Readout. Apply for EUL.
VGX-3100
? 2Q22: Start AIN, VIN P3’s. Receive ODD’s for both. Apply for Breakthrough Therapy Designation.
? 4Q22: Report REVEAL2 efficacy data and safety follow-up through week 40
INO-3107
? 2H22: ODD, Phase 1/2 immune responses and early clinical benefit data
Apply for Breakthrough Therapy Designation to be eligible for Priority Review Voucher which
can be sold to other BPs for $100M-$350M
INO-5401
? 2Q22: Present additional overall survival data OS36 including median OS for MGMT-methylated cohort
Platform Development
? 1H22: Report INO-4500 Lassa Phase 1b data
? 2H22: Report INO-4201 DARPA-sponsored Ebola Phase 1b booster data
? 2H22: Initiate COVID-19 dMAb trial
? 4Q22: MEDI0457 HNSCC P2 full data
December 2020, we and a team of scientists from The Wistar Institute, AstraZeneca, the University of Pennsylvania, and Indiana University received a $37.6 million grant from DARPA to use our DNA-encoded monoclonal antibody (dMAb) technology to develop anti-SARS-CoV-2-specific dMAbs which could offer versatile capabilities to function as both a therapeutic and preventive treatment for COVID-19.
As part of DARPA's two-year grant, our and Wistar's teams have constructed COVID-19 dMAb candidates mirroring AstraZeneca's traditional recombinant monoclonal antibody candidates currently being tested in clinical trials to treat COVID-19. These dMAb candidates can be quickly developed and produced in vivo, offering a cost-effective and scalable therapeutic and preventive option for treatment of SARS-CoV-2 virus infection. The dMAb® candidates will then be advanced into preclinical studies and then potentially into human clinical trials.
In October 2021, we announced that we have completed enrollment of a 220 participant Phase 1b trial in Accra, Ghana, which is the first vaccine clinical trial for Lassa Fever conducted in West Africa, where the viral illness is endemic. The dosing regimen involved two intradermal vaccinations at 0 and 28 days with either 1.0 mg or 2.0 mg doses. In addition to providing insights on the INO-4500 safety and immunogenicity profile, this trial will inform dose selection for subsequent Phase 2 trials in West Africa. If the result of this trial is positive, we expect to advance INO-4500 into a Phase 2 trial. If satisfactory Phase 2 data are achieved, CEPI, in cooperation with local regulatory authorities and the WHO, could elect to stockpile the vaccine for future use throughout the region.
In April 2018, we announced a collaboration with CEPI under which we are developing vaccine candidates against MERS. CEPI will fund up to $56 million of costs to support our pre-clinical and clinical advancement through Phase 2 of our vaccine candidate INO-4700. The goal of the collaboration is for our MERS vaccine to be available as soon as possible for emergency use.
We have dosed and completed enrollment for the first part (dose finding stage) of the Phase 2 trial (192 participants) of INO-4700. The multi-center Phase 2 trial is a randomized, double-blinded, placebo-controlled trial designed to evaluate the safety, tolerability, and immunogenicity of INO-4700 administered with CELLECTRA 2000 in approximately 500 healthy adult participants. The trial, which is sponsored by INOVIO and fully funded by CEPI, is being conducted at sites in Jordan, Lebanon, and Kenya where MERS cases have been reported.
In December 2021, we announced complete enrollment of a 46-participant Phase 1b trial in which INO-4201 will be assessed as a heterologous booster in healthy volunteers previously vaccinated with rVSV-ZEBOV (Ervebo®), an FDA- and EMA- approved viral vector-based Ebola vaccine. To date INO-4201 has been well- tolerated and has not demonstrated systemic SAEs, such as fever, joint pain, and low white blood cell counts, that have been reported in association with some viral vector-based Ebola vaccines currently in development.
INO-5151 (INO-5150 + INO-9012) for the Treatment of Prostate Cancer
We are developing INO-5151, which consists of DNA plasmids targeting Prostate Specific Antigen (PSA) and Prostate Specific Membrane Antigen (PSMA), combined with INO-9112, the IL-12 plasmid, for the treatment of prostate cancer. In the United States in 2022, there will be an estimated 268,490 new cases of prostate cancer and about 34,500 deaths due to this cancer. We previously completed a Phase 1 trial of INO-5150, DNA plasmids targeting PSA and PSMA. Data from this trial have been presented at several annual meetings, most recently at the 2018 European Society for Medical Oncology (ESMO) congress and have suggested that men treated with INO-5150 on the trial experienced a slowing of PSA doubling time, an important indicator of potential clinical benefit. Data presented at these conferences also showed immunogenicity and tolerability of INO-5150.
In 2019, we announced a clinical collaboration with Parker Institute for Cancer Immunotherapy (PICI) and the Cancer Research Institute (CRI) as part of which INO-5151 is being combined with an immune modulator (CDX-301, FLT3 ligand, a dendritic cell mobilizer) and a PD-1 immune checkpoint inhibitor (nivolumab) in participants with metastatic castration-resistant prostate cancer (mCRPC), in a PICI-sponsored platform trial (PORTER). This combination trial is an open-label, non- randomized, exploratory platform trial designed to assess the safety and antitumor activity of multiple immunotherapy-based combinations in participants with mCRPC who have received prior secondary androgen inhibition. This trial will evaluate biomarkers of immune activity and clinical outcomes using a multi-omic, multi- parameter approach. Our immunotherapy is one arm of this PICI-supported trial, and recruitment is ongoing. Under the agreement, PICI will design and conduct the clinical trial, working in collaboration with its established network of clinical academic and industry cancer centers, with funding support from CRI. We will provide financial contributions based on the actual costs of the trial, if INO-5151 reaches the initiation of a Phase 3 trial.
Following the termination of the Collaboration Agreement, the Company will reacquire the rights to INO-3112 and will no longer be entitled to receive potential future milestone payments or royalties under the Collaboration Agreement. The Company will also cease any development activities for which it would be entitled to seek reimbursement from MedImmune. The parties will continue to have rights to jointly publish work relating to the product candidate.
MedImmune is currently conducting a Phase 2 clinical trial of MEDI0457 in patients with head and neck squamous cell carcinomas (HNSCC). MedImmune has completed the final data cut off for the trial and plans to complete the clinical study report by the end of 2022. The Company expects that MedImmune will continue to sponsor this study until study termination. MedImmune will also continue providing financial support for an externally sponsored research study of MEDI0457 with The University of Texas MD Anderson Cancer Center until study completion.
10-K pg 38: We may seek a breakthrough therapy designation for one or more of our investigational medicines. A breakthrough therapy is defined as a drug that is intended, alone or in combination with one or more other drugs, to treat a serious or life-threatening disease or condition, and preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints, such as substantial treatment effects observed early in clinical development. For drugs that have been designated as breakthrough therapies, interaction and communication between the FDA and the sponsor of the trial can help to identify the most efficient path for clinical development while minimizing the number of patients placed in ineffective control regimens. Drugs designated as breakthrough therapies by the FDA are also eligible for priority review if supported by clinical data at the time of the regulatory submission.
INO-3107 RRP (ODD), INO-5401 GBM, VGX-3100 AIN, VIN, INO-4500 Lassa fever, INO-4700 MERS, Ebola, Zika, Dengue, Chikungunya may qualify for breakthrough therapy designation and Priority Review Vouchers worth
$100M-$350M each. On 3/3/22, there was an update of RRP
https://clinicaltrials.gov/ct2/history/NCT04398433?A=21&B=22&C=merged#StudyPageTop
In November 2020, additional data from the trial were presented at the Society for Neuro-Oncology (SNO) Annual Meeting. Survival data at 18 months showed that 70% (14/20) of MGMT promoter methylated GBM participants were alive, and 50% (16/32) of MGMT promoter unmethylated participants were alive after 18 months. In the MGMT promoter methylated cohort, 16 of 17 (94%) participants had an IFN-gamma response that increased over baseline to one or more of the antigens encoded by INO-5401.
In November 2021, updated data was presented at the Society for Immunotherapy of Cancer pre-conference workshop from the GBM-001 Phase 2 trial. Overall survival at 24 months was 22% (7/32) for the MGMT unmethylated cohort and 55% (11/20) for the MGMT methylated cohort. 12 mos have elapsed between Nov 2020-Nov 2021. So, OS18+12=OS30. In April 2022, OS36 should be available. If median OS for methylated cohort =36 > SoC=24, patients might Apply for Compassionate Use w/ FDA.
3/1/22 10-K: In addition to the upfront payment that we received in 2018, we are entitled to receive up to an aggregate of $20.0 million, less required income, withholding or other taxes, upon the achievement of specified milestones related to the regulatory approval of VGX-3100 in accordance with the Amended and Restated License and Collaboration Agreement. In the event that VGX-3100 is approved for marketing in these territories, we will be entitled to receive royalty payments based on a tiered percentage of annual net sales, with such percentage being in the low- to mid-teens. ApolloBio’s obligation to pay royalties will continue for 10 years after the first commercial sale in a particular territory.
12/14/21 - Phase 3 Trial in China – The first participant has been dosed in the Phase 3 trial of VGX-3100 for cervical HSIL in China. This trial is being run by ApolloBio and is similar in design to REVEAL2. The trial is expected to enroll up to 84 participants.
We are evaluating future clinical steps for the vulvar HSIL program, including the potential for applying for U.S. FDA Orphan Drug Designation (ODD) for this indication. ODD is intended to encourage drug development for rare diseases by providing tax credits for qualified clinical trials, an exemption from user fees related to the New Drug Application or Biological License Application, and a potential of up to seven years of market exclusivity after approval. The FDA grants orphan drug status to medicines intended for the prevention, diagnosis, and treatment of rare diseases or conditions, as defined as a disease or condition with a prevalence of less than 200,000 patients in the United States annually.
We plan to pursue a registrational Phase 3 clinical trial for HPV-16-/18-associated anal HSIL as well as to apply for ODD from the U.S. FDA.
We have completed a Phase 2 clinical trial (HPV-203) to evaluate VGX-3100 in participants who are HIV-negative with histologically confirmed anal or perianal HSIL, or anal intraepithelial neoplasia (AIN), associated with HPV-16 and/or HPV-18. This open-label trial enrolled 24 participants who received three doses of VGX- 3100 delivered by our CELLECTRA®-5PSP device. The primary endpoint of the trial was histologic clearance of the high-grade lesions and virologic clearance of the HPV-16/18 virus in anal/perianal tissue samples. In December 2020, we announced positive Phase 2 efficacy results from this trial. One-half of participants treated with VGX-3100 (11/22) showed resolution of HPV-16/18-associated anal HSIL at six months following the start of treatment. VGX-3100 was well-tolerated in the trial. We plan to pursue a registrational Phase 3 clinical trial for HPV-16-/18-associated anal HSIL as well as to apply for ODD from the U.S. FDA.
In addition to the Phase 2 anal HSIL trial sponsored by us, a separate ongoing Phase 2 trial sponsored by the AIDS Malignancy Consortium (AMC-103) is evaluating VGX-3100 in participants with histologically confirmed anal or perianal HSIL associated with HPV-16 and/or HPV-18 who are HIV-positive. This open- label single-arm trial plans to enroll approximately 75 participants who will receive up to four doses of VGX-3100 delivered by CELLECTRA®-5PSP smart device. The primary endpoint of the trial is histological regression of high-grade anal lesions to low-grade SIL or normal histology.
We have also completed a Phase 2 trial (HPV-201) to evaluate the efficacy of VGX-3100 in participants with vulvar HSIL. This randomized, open-label Phase 2 clinical trial assessed the efficacy of VGX-3100 in 33 women with vulvar HSIL. VGX-3100 was administered with our CELLECTRA® -5PSP smart device. The primary endpoint of the trial was histologic clearance of high-grade lesions and virologic clearance of the HPV virus in vulvar tissue samples. The trial also evaluated the safety and tolerability of VGX-3100. In January 2021, we announced positive efficacy results from this trial. A 25% or more reduction in HPV-16/18-associated vulvar HSIL was observed for 63% of trial participants (12 of 19) treated with VGX-3100 at six months post-treatment. Three of the 20 participants with histology data (15%) resolved their vulvar HSIL and had no HPV-16/18 virus detectable in the healed area. VGX-3100 was well-tolerated in the Phase 2 trial.
We are evaluating future clinical steps for the vulvar HSIL program, including the potential for applying for U.S. FDA Orphan Drug Designation (ODD) for this indication. ODD is intended to encourage drug development for rare diseases by providing tax credits for qualified clinical trials, an exemption from user fees related to the New Drug Application or Biological License Application, and a potential of up to seven years of market exclusivity after approval. The FDA grants orphan drug status to medicines intended for the prevention, diagnosis, and treatment of rare diseases or conditions, as defined as a disease or condition with a prevalence of less than 200,000 patients in the United States annually.
10-K
FDA awards a voucher following approval of a treatment for a neglected disease, rare pediatric disease, or medical countermeasure.
Upon NDA approval, ODD’ed AIN, VIN will get a Priority Review Voucher each, which has been sold for $50M-$350M.
https://sites.fuqua.duke.edu/priorityreviewvoucher/value/
In 2014, Regeneron Pharmaceuticals and Sanofi purchased a PRV that BioMarin had won for a recent rare disease drug approval for $67.5 million; the voucher cut four months off the regulatory review time for alirocumab and was part of their strategy to beat Amgen to market with the first approval of a PCSK9 inhibitor.[30][31][32] In 2015, Retrophin sold a PRV to Sanofi for around $245 million, and later the same year, United Therapeutics Corp. sold a PRV for a drug for a rare pediatric disease to AbbVie Inc. for $350 million.[33] In 2016–2018, the value of a voucher ranged from $125 million to $200 million, down from its peak in 2015.
Priority Review Vouchers for rare pediatric diseases, issued and sold 2012-present
https://www.kidsvcancer.org/priority-review-vouchers/
3/2/22 Updated IR deck Heterologous Boost Market Potential
https://s23.q4cdn.com/479936946/files/doc_presentations/2022/03/INOVIO-Investor-Deck-Presentation-220301.pdf
• Booster market is much larger than primary vaccine market
• Inactivated and viral vector vaccines have been administered primarily in Low- and Middle- Income countries
• About 2.4 billion doses of the Chinese vaccines have been administered in China, but almost 1 billion doses have gone to 110 other countries
• Global demand for heterologous boosters cannot be met with currently licensed (EUA or full authorization) for primary series or those not currently licensed but with Phase 3 data efficacy data
• Market reset focused now on heterologous boost
Path Forward
• Evaluating the feasibility of an additional ex-US heterologous boost trial with INO-4800 as a booster in a non-inferiority clinical trial compared to viral and inactivated COVID-19 vaccines
Global Demand
• Currently licensed vaccines may not meet the global demand for boosters to address waning protection from these primary vaccinations
Key Features
• INOVIO’s DNA vaccine technology make it a potential booster candidate including:
? Cross-reactive T-cell responses
? Tolerability of re-administration
? Thermostability for transport, storage, and distribution
Boosting Experience
• INOVIO has previous experience with heterologous boosting; Ebola (INO-4201) boost trial ongoing
INO-4800 Clinical Pathways & Global Presence
INNOVATE Global Phase 3 Trial
• INOVIO with Advaccine are jointly conducting a global Phase 3 trial for INO-4800
o Healthy men and non-pregnant women 18 years and older (2.0 mg dose)
o Focus on countries currently underserved by vaccines in Latin America and Asia
INOVIO is seeking to amend the primary endpoint of INNOVATE from prevention of virologically confirmed COVID-19 disease to prevention of severe disease
o While dosing may continue for participants who have already received administration, INOVIO has paused enrollment of new participants in INNOVATE
WHO-Sponsored Solidarity Trial Vaccines
• Global Phase 3 placebo-controlled trial will enroll 40,000 participants
• Trial represents the largest global clinical trial for COVID-19 vaccine candidates
• INO-4800 was selected by the WHO’s independent vaccine prioritization advisory group
Heterologous and Homologous Booster Trials with Advaccine in China
• 267-participant heterologous boost Phase 1/2 clinical trial evaluating safety, tolerability, immunogenicity of INO-4800 in participants who previously received inactivated virus COVID-19 vaccines as a primary vaccine
• 200-participant homologous boost Phase 1/2 clinical trial evaluating safety, tolerability, immunogenicity of INO-4800 in participants who previously received INO-4800 as a primary vaccine
INO-4800
? 1Q22: Completed enrollment of heterologous and homologous boost Phase 1/2 trials in China with Advaccine
VGX-3100
? 4Q22: Report REVEAL2 efficacy data and safety follow-up through week 40 INO-3107
? 2H22: Phase 1/2 immune responses and early clinical benefit data INO-5401
? 2022: Present additional overall survival data including median OS for MGMT-methylated cohort
Platform Development
? 1H22: Report INO-4500 Lassa Phase 1b data
? 2H22: Report INO-4201 Ebola Phase 1b booster data
? 2H22: Initiate COVID-19 dMAb trial
INO-4500 for Lassa Fever
• Phase 1b clinical trial
• Completed enrollment of 220 participants
• Funded by CEPI
• Conducted in Ghana
INO-4700 for MERS
• Phase 2 clinical trial in approximately 500 participants
• Completed enrollment for dose-finding stage (192 participants)
• Funded by the CEPI
• Conducted at sites in Jordan, Lebanon, and Kenya
INO-4201 for Ebola
• Phase 1b clinical trial
• Completed enrollment of 46 participants
• Funded by DARPA
• Evaluating INO-4201 as a booster in participants previously
vaccinated with Ervebo®
3/1/22 Booster critical as COVID-19 vaccine-induced antibodies wane in 6 months, don’t protect against omicron
In studies, a third booster shot enhances immune response
The Ohio State University
https://news.osu.edu/booster-critical-as-covid-19-vaccine-induced-antibodies-wane-in-6-months-dont-protect-against-omicron/
Neutralization and Stability of SARS-CoV-2 Omicron Variant
https://www.biorxiv.org/content/10.1101/2021.12.16.472934v1
A new study using serum from human blood samples suggests neutralizing antibody levels produced by two-dose mRNA vaccines against the original and early variants of the SARS-CoV-2 virus wane substantially over time, and offer essentially no protection against the omicron variant.
The same Ohio State University lab found in a previous study, posted on the preprint server bioRxiv, that a third COVID-19 mRNA vaccine booster shot did produce effective levels of neutralizing antibodies against omicron. This study has not yet been peer-reviewed.
“Our new work shows that two doses of mRNA vaccine do not offer protection against omicron, and even having a breakthrough infection on top of vaccine does not help much. But our earlier study showed that the booster can really rescue the shortcomings of the two doses,” said Shan-Lu Liu, the senior author of both studies and a virology professor in the Department of Veterinary Biosciences at Ohio State.
The new research is published online as a First Release paper in the journal Science Translational Medicine.
The researchers examined antibodies in serum samples from 48 health care professionals with experimental versions of the parent virus and the alpha, beta, delta and omicron variants. Serum samples were collected pre-vaccination, three to four weeks after a first vaccine dose, three to four weeks after a second vaccine dose and six months after the second vaccine.
“There was a substantial increase in neutralizing antibodies after the second dose against every variant except the omicron variant,” said first study author John Evans, a PhD student in Ohio State’s Molecular, Cellular and Developmental Biology Program who works in Liu’s lab. “From the second dose to six months later, there was an at least five-fold drop in immunity, even against the parent virus.”
Neutralizing antibodies that block viral particles’ entry into host cells are considered the gold standard of protection against COVID-19 infection.
Twelve of the samples came from people suspected to have had a COVID-19 infection – at time points ranging from before vaccination to after two vaccine doses – based on a different kind of antibody testing. And though the findings suggested a breakthrough COVID-19 infection on top of vaccination increased immunity against most versions of the virus, antibodies from only one individual with previous infection reached levels that could put up a reasonable fight against omicron.
“Overall, nobody in this study had good immunity against omicron,” said Liu, also an investigator in the university’s Center for Retrovirus Research and a program co-director of the Viruses and Emerging Pathogens Program in Ohio State’s Infectious Diseases Institute.
The experimental viruses were what are called pseudoviruses – a non-infectious viral core decorated with different SARS-CoV-2 spike proteins on the surface structured to match known mutations in the variants studied.
The researchers used a special method to detect neutralizing antibodies in the health professionals’ blood samples to account for the varying levels of antibodies produced by individuals.
“Individuals did respond very differently to the first dose, and the same was true for the second dose,” Liu said.
Results also showed that people who received the Pfizer-BioNTech mRNA vaccine produced about two-fold lower levels of neutralizing antibodies than those who received the Moderna vaccine. Men also had significantly higher antibody levels compared to women against all variants over the post-vaccination time points.
Liu said the dramatic reduction in immunity six months after two vaccine doses and the earlier paper’s finding that a booster protects against omicron highlight how important a third shot is to avoiding infection.
“After the second vaccine dose, the neutralizing antibodies effective against omicron dropped 23-fold, but with a booster shot, immunity dropped only three- to four-fold – which is comparable to booster effectiveness previously reported against the delta variant,” he said. “Similar observations have been made by other labs.”
Additional co-authors of the Science Translational Medicine study, all from Ohio State, include Cong Zeng, Claire Carlin, Gerard Lozanski, Linda Saif, Eugene Oltz and Richard Gumina. Additional co-authors on the bioRxiv preprint include Panke Qu, Julia Faraone, Yi-Min Zheng, Joseph S. Bednash, Rama Mallampalli, Peter Mohler and Kai Xu of Ohio State and Tongqing Zhou from NIH.
This work was supported by anonymous donor funds, grants from the National Institutes of Health, the Glenn Barber Fellowship from Ohio State’s College of Veterinary Medicine, the National Cancer Institute and the Robert J. Anthony Fund for Cardiovascular Research.
Booster critical as COVID-19 vaccine-induced antibodies wane in 6 months, don’t protect against omicron
New study from Sweden says, Pfizer mRNA does indeed integrate into our DNA
https://www.riotimesonline.com/brazil-news/modern-day-censorship/new-study-from-sweden-says-pfizer-mrna-does-indeed-integrate-into-your-dna/amp/
Intracellular Reverse Transcription of Pfizer BioNTech COVID-19 mRNA Vaccine BNT162b2 In Vitro in Human Liver Cell Line
Curr. Issues Mol. Biol. 2022, 44, 1115–1126.
Received: 18 January 2022 Accepted: 23 February 2022 Published: 25 February 2022
https://www.riotimesonline.com/wp-content/uploads/2022/02/Pfizer-RNA-into-DNA.pdf
RIO DE JANEIRO, BRAZIL – Swedish lab studies show that mRNA from the ‘vaccines’ does integrate itself into human cellular DNA. This means that a shot of the Pfizer vaccine, taken even once, permanently changes the DNA of affected cells.
For over a year, we’ve been told that mRNA vaccines, including Pfizer and Moderna, don’t integrate with human cell DNA.
What the article shows is that in vitro, using a human liver cell line, the Pfizer mRNA vaccine uses a natural reverse transcriptase enzyme called LINE-1, and the genetic code of the vaccine is reverse transcribed into the DNA.
It also explains that vaccine mRNA actually does travel to the liver as one of the preferred sites (the other sites, as we heard, are ovaries and more).
What does it mean? Normally, our cells do the reverse: the cell nucleus, where the DNA is, expresses certain DNA code based on conditions of the cell and produces natural, human messenger RNA.
That messenger RNA travels out of the nucleus, where it is expressed into proteins needed for cell building. This is how growing organisms express different genetic programs to grow muscle cells or brain cells, etc.
This process is called “transcription”.
For many years, Central Dogma of Molecular Biology stated that the “reverse transcription” — moving genetic code from RNA back into the sacred cellular nuclear and recoding the DNA — was impossible.
Eventually, scientists realized that it is possible under various conditions. For example, the HIV RNA virus is able to do so and it reprograms our DNA to produce copies of it. HIV is the virus that causes AIDS.
To effect reverse transcription, enzymes called “reverse transcriptases” are needed. One of them is called LINE-1.
Apparently, the Pfizer mRNA vaccine causes cells to produce that LINE-1 enzyme, says the study.
After seeing LINE-1 reverse transcriptase rise, they tested for alterations to the DNA, making sure they are not picking up the RNA instead.
Considering that Sars-Cov-2 “spike protein” has a cancer code from Moderna 2017’ patent 9,587,003, it is imperative to find out the implications of this reverse transcription, and whether the vaccinated now have any undesirable genetic code embedded into their DNA.
Of particular interest is whether this mRNA-induced reverse transcription affects the “germ line”, such as eggs and sperm cells, and whether it also affects the fetus of pregnant mothers.
Advaccine’s 200-ppl homologous and 267-ppl heterologous boost interim data out next month, Apr 2022. So will the WHO’s STV.
Dr. Joseph Kim, 4Q21 CC, 3/1/22:
“Yes. So, thank you, Roger. The vaccine homologous and heterologous boost trials, that’s fully enrolled. They expect to have the data in the second quarter of this year. So, it’s of course being run and executed by our partner in China, Advaccine. So, we expect the data from that trial sometime in the next quarter.”
Taipei, Feb. 15 (CNA) The Taiwanese vaccine maker, Medigen Vaccine Biologics Corp., said Tuesday that a World Health Organization-led (WHO) clinical trial of its COVID-19 vaccine could be unblinded in March at the earliest.
The Medigen COVID-19 vaccine, a protein subunit vaccine, is currently being tested under the WHO's Phase 3 Solidarity Trial Vaccines program.
At a press conference, the Taiwanese company's Vice Chairman and CEO Charles Chen (???) said that unblinding of the clinical trial could take place as early as the end of March and would determine whether the WHO recommends the Medigen vaccine for use against COVID-19.
According to the WHO, research teams in Colombia, Mali, and the Philippines began recruiting volunteers for the Solidarity Trial Vaccines, which aims to "rapidly evaluate the efficacy and safety of promising new candidate vaccines against COVID-19," in late September 2021.
As of Dec. 22, 2021, over 11,500 people had registered to take part in the project, WHO data showed.
Chen said the validation of the Medigen vaccine following the clinical trial would further enhance the company's collaboration with the WHO, which has been working to make more vaccines available and accessible through the global vaccine sharing initiative, COVAX.
The WHO has so far issued an emergency use listing for 10 COVID-19 vaccines.
He added that WHO recognition would also facilitate the vaccine brand's expansion in the Central and South American as well as Southeast Asian markets, as it will increase the possibility of the Medigen vaccine being granted emergency use authorization (EUA) by other countries.
https://focustaiwan.tw/society/202202150024
Ino’s Ebola, Lassa fever, MERS, Zika vaccines eligible for Priority review vouchers (PRVs) worth $100M-$500M
PRV is issued to the sponsor of a rare pediatric disease product application and entitles the holder to priority review of a single New Drug Application or Biologics License Application. The sponsor receives the voucher upon approval of the rare pediatric disease product application. PRVs may be sold or transferred, and there is no limit on the number of times a PRV can be transferred.
The FDA goal for reviewing a drug with Priority Review status is six months from the time the application is filed by the FDA, compared to 10 months under standard review.
Extension to Ebola virus
In December 2014, the Senate approved a bill that would add the Ebola virus to the Priority Review Voucher List.[23] The bill, S. 2917—Adding Ebola to the FDA Priority Review Voucher Program Act, was introduced by Senator Tom Harkin on November 12, 2014. President Obama signed it on December 16, and it became Public Law 113-233.[24] Forty-five Senators cosponsored the bill (26 Democrats and 19 Republicans).[25] This act also eliminated the differences between tropical disease and pediatric disease vouchers, but allowing both to be sold an unlimited number of times and be used after a 90-day notification period to the FDA.
On a technical level, S. 2917 added "Filoviruses" to the priority review list. The Ebola virus is a type of Filovirus. According to the Congressional Budget Office, enactment of the law does not have an effect on the federal budget.[26]
Extension for medical countermeasures Edit
The Senate's Medical Countermeasure Innovation Act of 2016 proposed adding a new category of drugs to the priority review voucher program. In 2016, it was confirmed that the approval of drugs for medical countermeasures would be eligible to earn a priority review voucher. Medical countermeasures are drugs to "prevent or treat harm from a biological, chemical, radiological or nuclear agent identified as a material threat".[27]
The eligible tropical diseases include the following:[3][35]
Blinding trachoma
Buruli ulcer
Chagas disease (added in 2015)
Cholera
Chikungunya virus disease (added in 2018 final order)
Cryptococcal meningitis (added in 2018 final order)
Dengue/dengue haemorrhagic fever
Dracunculiasis (guinea-worm disease)
Fascioliasis
Filovirus diseases (including Ebola virus disease) (added in 2014 by Pub. L. 113-233, amended by Pub. L. 114-146)
Human African trypanosomiasis
Lassa fever (added in 2018 final order)
Leishmaniasis
Leprosy
Lymphatic filariasis
Malaria
Neurocysticercosis (added in 2015)
Onchocerciasis
Rabies (added in 2018 final order)
Schistosomiasis
Soil-transmitted helminthiasis
Tuberculosis
Yaws
Zika virus disease (added in 2016 by Pub. L. 114-146)
Any other infectious disease for which there is no significant market in developed nations and that disproportionately affects poor and marginalized populations, designated by order of the Secretary.
Pediatric rare diseases are any disease that primarily affects people under the age of 18 and affects 200,000 or fewer people in the United States. Medical countermeasures are drugs to be used "in the event of a public health emergency stemming from a terrorist attack with a biological, chemical, or radiological/nuclear material, a naturally occurring emerging disease, or a natural disaster
https://en.m.wikipedia.org/wiki/Priority_review
We are evaluating future clinical steps for the vulvar HSIL program, including the potential for applying for Orphan Drug Designation (ODD) for this indication. ODD is intended to encourage drug development for rare diseases by providing tax credits for qualified clinical trials, an exemption from user fees related to the New Drug Application or Biological License Application, and a potential of up to seven years of market exclusivity after approval. The FDA grants ODD status to medicines intended for the prevention, diagnosis, and treatment of rare diseases or conditions, as defined as a disease or condition with a prevalence of less than 200K patients in the US annually.
In Dec 2021, we announced that we and QIAGEN have identified candidate biomarker signatures for VGX-3100 with the intent of selecting a final signature of a pre-treatment in vitro diagnostic to meet the specific characteristics desired to identify women with HPV-16/18 cervical HSIL most likely to respond.
Stephen Willey of Stifel
Are you able to say how many patients were enrolled into INNOVATE at the time of the pause?
Dr. Joseph Kim
Yes. No, we -- it’s our policy not to provide up to date information. But we were -- we have significant number of volunteers who have been dosed. And they will continue to receive the second dose and follow during the pause period. It’s just the new enrollment that’s paused.
Dr. Joseph Kim
while it is true that the severity of Omicron infection has been reduced by I believe, 50% to 75% of Delta, we believe the higher incidences of infections will equalize out. But, so your point about the severe disease incidences being a major driver of us getting the endpoint, I think that’s a fair one. We are and we have evaluated those impacts, and we expect the sample size to be around 7,000 to 10,000, as we had projected initially with our INNOVATE trial. And as I mentioned, we will be continually monitoring those severe disease rates across these territories. But I think we feel fairly good that we should be able to achieve our objectives going forward.
Peter Kies
No. We have ongoing efforts in a lot of areas going on with this. So, I think you’re going to see it remain fairly consistent with the other quarters, running in the $65 million burn range about, per quarter.
Dr. Joseph Kim
Yes. So, thank you, Roger. The vaccine homologous and heterologous boost trials, that’s fully enrolled. They expect to have the data in the second quarter of this year. So, it’s of course being run and executed by our partner in China, Advaccine. So, we expect the data from that trial sometime in the next quarter.
In terms of additional heterologous boost, we’re deeply investigating the feasibility and execution ability of a heterologous boost trial, again outside the U.S. where we can compare with two other most prolifically utilized primary vaccine for COVID in viral vector and inactivated vaccines. So, we’re in the planning and feasibility stage. But, if this is a go, we think we can execute this all through 2022.
Dr. Kate Broderick
We certainly are very excited about what our pan-coronavirus vaccine INO-4802 has shown pre-clinically and we continue to develop it. But really what’s particularly striking about our COVID vaccines across the board, including INO-4800 is this pan-COVID T cell response that we’re able to generate thus far. So, even in the face of the wrench in the works that was Omicron, we’re still maintaining those all important T-cell responses. So, we’re very excited and very encouraged about what our vaccines are able to generate.
Yi Chen
And my last question is, when do you expect to report results from Phase 2 trial of 4700 to MERS vaccine?
Dr. Kate Broderick
we’re currently still enrolling, and at the moment, we’re about halfway through now. So, probably by Q3 of this year.
Yi Chen
And the next question is, with respect to 5401 in GBM, what is the next step and what are the expected catalysts for this program this year?
Dr. Joseph Kim
we’ll continue to follow them, we’re evaluating our next steps with our collaborator Regeneron. So, I think overall survival, as well as the following of these surviving participants will give us additional insights into the path forward for this program.
We fully enrolled about 200 participants in REVEAL2 in the fourth quarter as the last patient in 40 weeks of trial follow-up. So, our projection is we would have preliminary data safety and immunogenicity and efficacy in the fourth quarter of 2022. And no, we haven’t had any changes to REVEAL2 protocol. It’s identical to REVEAL1 except the follow-up, safety follow-up is one month instead of one year.
the steps to getting the primary endpoint amended is modifying and amending the protocol and getting them approved through various regulators who are overseeing the INNOVATE trial in their respective countries. So, we expect that to occur in the next as expediently as possible across these regulatory bodies and their local ethics committees. We think, we have a strong position, and because of our T cell maintenance against Omicron as well as other variants of concern, I think we have a very strong case in that regard.
WHO only speaks for WHO. So, we’re not privy to speaking for them. But, what I can tell you is Omicron has equally impacted all vaccines being developed and trials currently undergoing. So, as you know, Solidarity Trial Vaccines is run and sponsored by the WHO and. And they have the full control. And we have full confidence that they will be able to execute the trial as they see most appropriately. So, so far, everything is moving as they had stated in the fall.
What’s great about our Omicron data as described by Kate and myself earlier is that our T cell responses, including CD8 killer T cells were fully maintained against Omicron. So, that really leads us to believe that whether we’re targeting the original variants Alpha, Beta, Gamma, Delta, or even Omicron, or even what’s next, right, the stealth Omicron or the next variant, we have full faith that our CD8 T cell responses and our overall T cell responses generated from INO-4800 is going to persist and be maintained.
So, with that in mind, we are taking a proactive step knowing that our probability of success in demonstrating prevention of severe disease with our vaccine against COVID-19 virus is high. And that’s the label that we would look for and all of the other attributes and target profile that we have mentioned earlier. We believe our INO-4800 has a strong position once we get the Phase 3 data, and once we get the emergency and full licensure to demonstrate this -- benefits as a vaccine against SARS-CoV-2.
Q4 2021 Results 3/1/22
No Omicron immunity without booster, study finds
Traditional regimens of COVID-19 vaccines do not neutralize the fast-spreading variant
MGH News and Public Affairs
January 7, 2022
An additional “booster” dose of Moderna or Pfizer mRNA-based vaccine is needed to provide immunity against the Omicron variant of SARS-CoV-2, the virus that causes COVID-19, according to a study by researchers at the Ragon Institute of MGH, MIT and Harvard. The results of this study, reported in the journal Cell, indicate that traditional dosing regimens of COVID-19 vaccines available in the United States do not produce antibodies capable of recognizing and neutralizing the Omicron variant.
In late November, health officials in South Africa reported that a previously unknown variant of SARS-CoV-2 was rapidly spreading throughout the country. The variant, given the name Omicron by the World Health Organization, would soon prove to be far more transmissible than Delta, the variant that previously had caused the majority of COVID-19 infections. “People desperately wanted to know whether current vaccines protect against Omicron,” says the senior author of the Cell paper, Alejandro Balazs, whose laboratory at the Ragon Institute investigates how to engineer immunity against infectious diseases.
To find answers, Balazs collaborated with a team that included the lead author of the Cell paper, Wilfredo F. Garcia-Beltran, a clinical pathology resident at MGH and a clinician-scientist fellow at the Ragon Institute. The first step was to construct a harmless version of Omicron known as a “pseudovirus” that could be used in the laboratory to evaluate the effectiveness of the three COVID-19 vaccines available in the United States, which include the two-dose Pfizer and Moderna injections and the one-dose Johnson & Johnson vaccine. The pseudovirus that Balazs and colleagues created mimicked the behavior of Omicron, which has 34 mutations on its “spike” protein that are not found on the original strain of SARS-Cov-2 first detected in Wuhan, China, in December 2019. Scientists believe that these mutations may be partially responsible for Omicron’s rapid spread throughout the world.
Next, Garcia-Beltran worked with colleagues at MGH, including hematology-oncology fellow Vivek Naranbhai, to acquire blood samples from 239 individuals who had been fully vaccinated with one of the three COVID-19 vaccines. The study subjects included employees within the Massachusetts General Brigham health care system and residents of Chelsea, Massachusetts, a community with a high rate of COVID-19 infections. “It was important to us to have a diverse population represented in the study,” says Garcia-Beltran. Included in this group were 70 men and women who had received a third booster dose of either the Pfizer or Moderna vaccine, according to recommendations by the Centers for Disease Control and Prevention.
The blood samples were used to measure how effectively each vaccine induces production of protective immunity in the form of antibodies against the Omicron pseudovirus, as well as the Delta and wild type viruses. The results were striking. “We detected very little neutralization of the Omicron variant pseudovirus when we used samples taken from people who were recently vaccinated with two doses of mRNA vaccine or one dose of Johnson & Johnson,” says Balazs. “But individuals who received three doses of mRNA vaccine had very significant neutralization against the Omicron variant.”
It’s not yet clear why an mRNA booster dramatically improves immune protection against Omicron, but Garcia-Beltran says one possibility is that an additional dose creates antibodies that bind more tightly to the spike protein, increasing their effectiveness. Also, a booster dose may generate antibodies that target regions of the spike protein that are common to all forms of SARS-CoV-2. Both theories may be true, says Garcia-Beltran.
Balazs notes that the three-dose mRNA vaccine regimen — that is, the traditional two doses and a booster of Pfizer or Moderna vaccines — provides somewhat lower levels of neutralizing antibodies against Omicron than it does against the COVID-19 wild type strain or Delta variant. But the study’s results strongly support the CDC’s advice that COVID-19 booster shots are appropriate for anyone 16 and older, and that mRNA vaccines are preferred.
Balazs is a principal investigator at the Ragon Institute and an assistant professor of Medicine at Harvard Medical School. Garcia-Beltran recently established his own laboratory at the Ragon Institute.
This work was supported by the Peter and Ann Lambertus Family Foundation, the Massachusetts Consortium on Pathogenesis Readiness, the National Institutes of Health, and the German Center for Infection Research.
https://news.harvard.edu/gazette/story/2022/01/no-omicron-immunity-without-booster-study-finds/
https://www.cell.com/cell/fulltext/S0092-8674(21)01496-3
FactWire: Sinovac limits Hong Kong’s protection against infection from Omicron, analysis suggests
After receiving a booster, the effectiveness of three doses of the BioNTech vaccine may be as high as 89 per cent, whereas three doses of Sinovac may only be 36 per cent effective. That’s why Sinovac needs 4800 booster.
https://news.google.com/articles/CBMigQFodHRwczovL2hvbmdrb25nZnAuY29tLzIwMjIvMDIvMjYvZmFjdHdpcmUtc2lub3ZhYy1saW1pdHMtaG9uZy1rb25ncy1wcm90ZWN0aW9uLWFnYWluc3QtaW5mZWN0aW9uLWZyb20tb21pY3Jvbi1hbmFseXNpcy1zdWdnZXN0cy_SAYEBaHR0cHM6Ly9ob25na29uZ2ZwLmNvbS8yMDIyLzAyLzI2L2ZhY3R3aXJlLXNpbm92YWMtbGltaXRzLWhvbmcta29uZ3MtcHJvdGVjdGlvbi1hZ2FpbnN0LWluZmVjdGlvbi1mcm9tLW9taWNyb24tYW5hbHlzaXMtc3VnZ2VzdHMv?hl=en-US&gl=US&ceid=US%3Aen
3Q21, 10-Q ,
pg 15
The June 2021 amendment relates to the collaboration between the Company and Advaccine to jointly conduct the global Phase 3 segment of the Company’s
ongoing Phase 2/3 trial of INO-4800 and expand the existing collaboration to include the planned global Phase 3 trial. The parties will jointly participate in the trial and
will equally share the global development costs for the trial, including the Company’s manufacturing costs to supply INO-4800. In certain instances, the Company will
have the right to convert the exclusive license to a non-exclusive license in the licensed territories, other than Greater China, unless Advaccine agrees to pay the Company
its full share of development costs in excess of a specified maximum. Notwithstanding the foregoing, Advaccine will be fully responsible for conducting the trial in
Greater China, including its costs and expenses incurred in conducting the trial in Greater China. The Company will be fully responsible for its costs and expenses, if any,
incurred solely as a result of its activities in connection with the performance of the trial in the United States. The parties may continue to conduct clinical trials of INO-
4800 outside of the territories covered by the Advaccine Agreement.
In the event that a global purchasing entity desires to enter into a purchase agreement for INO-4800 in both parties’ territories, the parties will enter into good faith
negotiations for an arrangement to supply INO-4800 to such entity. In addition, the Company is permitted to enter into an agreement with a global purchasing entity to authorize the entity to conduct a portion of the global Phase 3 trial in the licensed territory outside of Greater China.
Under the Advaccine Agreement, Advaccine made an upfront payment to the Company of $3.0 million in January 2021. In addition to the upfront payment, the
Company is entitled to receive up to an aggregate of $206.0 million upon the achievement of specified milestones related to the development, regulatory approval and
commercialization of INO-4800, including the achievement of specified net sales thresholds for INO-4800 in Greater China and the additional covered territories, if
the product in the Advaccine territory. The Company will also be entitled to receive a royalty equal to a high single-digit percentage of annual net sales in each region
within the licensed territory, subject to reduction in the event of competition from biosimilar products in a particular region and in other specified circumstances.
Advaccine’s obligation to pay royalties will continue, on a licensed product-by-licensed product basis and region-by-region basis, for ten years after the first commercial
sale in a particular region within Greater China or, if later, until the expiration of the last-to-expire patent covering a given licensed product in a given region.
Beginning in the first calendar year following the first commercial sale of INO-4800 in the licensed territory outside of Greater China, Advaccine will pay the
Company an annual maintenance fee of $1.5 million for a period of five years, which fee will be creditable against any royalties payable by Advaccine with respect to
sales outside of Greater China.
Under the Advaccine Agreement, the Company will supply Advaccine’s clinical requirements of INO-4800 and devices, although Advaccine may manufacture
INO-4800 for its clinical use and may procure alternate suppliers. Advaccine is responsible for the manufacture and supply of INO-4800 itself or through a contract
manufacturer for commercial use. Upon Advaccine’s reasonable request, the parties may negotiate a separate clinical and/or commercial supply agreement.
2/25/22 Su News (Reporter Lu Xiaohua and Zhang Xiaoliang) Recently, the Ministry of Science and Technology issued the "Decision on Recognizing Advanced Groups and Individuals in the National Science and Technology System's Fight against the New Coronary Pneumonia Epidemic", and awarded 163 collectives across the country the title of "National Science and Technology System Advanced Group in Fighting the New Coronary Pneumonia Epidemic". 314 people were awarded the title of "Advanced Individual in the National Science and Technology System's Fight against the New Coronary Pneumonia Epidemic". Aidi Weixin (Suzhou) Biopharmaceutical Co., Ltd. and Key Laboratory of Biomedical Testing Technology of Suzhou Institute of Biomedical Engineering Technology, Chinese Academy of Sciences were awarded the title of advanced collective.
The reporter learned that, as an innovative vaccine company, Aidi Weixin has established a comprehensive technology platform for the design and development of DNA vaccines, large-scale production processes, high-purity plasmid production, and new delivery technologies, and ranks among the world in related fields. At the forefront, it has completed its phased mission in terms of public health security risk prevention and control and advanced technology being independent, autonomous, and controllable.
The new crown DNA vaccine pGX9501 developed by Ai Weixin is a deoxyribonucleic acid vaccine based on circular DNA plasmids. It has completed Phase I and Phase II clinical studies in China and the United States, and is conducting Phase III clinical studies in multiple countries and centers around the world. It was selected by the World Health Organization as the global new crown vaccine solidarity test variety, and the sequential immunization clinical research with inactivated vaccine is also underway. At present, Aidi Weixin has built a GMP production line for the new crown DNA vaccine, obtained a vaccine production license, and has deployed dozens of patents related to the new crown vaccine worldwide, targeting the known variants of the new coronavirus and potential future variants. Broad-spectrum vaccine candidates are also in full swing.
http://www.subaonet.com/2022/szyw/0225/456262.shtml
2/25/22 Su News (Reporter Lu Xiaohua and Zhang Xiaoliang) Recently, the Ministry of Science and Technology issued the "Decision on Recognizing Advanced Groups and Individuals in the National Science and Technology System's Fight against the New Coronary Pneumonia Epidemic", and awarded 163 collectives across the country the title of "National Science and Technology System Advanced Group in Fighting the New Coronary Pneumonia Epidemic". 314 people were awarded the title of "Advanced Individual in the National Science and Technology System's Fight against the New Coronary Pneumonia Epidemic". Aidi Weixin (Suzhou) Biopharmaceutical Co., Ltd. and Key Laboratory of Biomedical Testing Technology of Suzhou Institute of Biomedical Engineering Technology, Chinese Academy of Sciences were awarded the title of advanced collective.
The reporter learned that, as an innovative vaccine company, Aidi Weixin has established a comprehensive technology platform for the design and development of DNA vaccines, large-scale production processes, high-purity plasmid production, and new delivery technologies, and ranks among the world in related fields. At the forefront, it has completed its phased mission in terms of public health security risk prevention and control and advanced technology being independent, autonomous, and controllable.
The new crown DNA vaccine pGX9501 [INO-4800] developed by Ai Weixin is a deoxyribonucleic acid vaccine based on circular DNA plasmids. It has completed Phase I and Phase II clinical studies in China and the United States, and is conducting Phase III clinical studies in multiple countries and centers around the world. It was selected by the World Health Organization as the global new crown vaccine solidarity test variety, and the sequential immunization clinical research with inactivated vaccine is also underway. At present, Aidi Weixin has built a GMP production line for the new crown [Corona] DNA vaccine, obtained a vaccine production license, and has deployed dozens of patents related to the new crown vaccine worldwide, targeting the known variants of the new coronavirus and potential future variants. Broad-spectrum vaccine candidates are also in full swing.
http://www.subaonet.com/2022/szyw/0225/456262.shtml
2/8/22 investor.relations@inovioasia.com
”I believe Advaccine is planning to go IPO this year. However, that will most likely depend on clinical progress as well as market condition. While INOVIO is not the sponsor, I did hear that heterologous boost and homologous boost trial is progressing.”
1/27/22 “I cannot speak for them but I understand it is proceeding well. I am sure Advaccine will announce something when ready.”
https://www.chictr.org.cn/hvshowproject.aspx?id=119337
1/25/22 “We are in the process of updating our deck.”
2/25/22 (Covid over? Not by a long shot!)- SEOUL, South Korea -- South Korea saw its deadliest day of the pandemic on Saturday, reporting 112 fatalities in the latest 24-hour period, as it grapples with a wave of coronavirus infections driven by the fast-moving omicron variant. Health workers diagnosed 166,209 new cases, which came close to Wednesday’s one-day record of 171,451 and represented more than a 37-fold increase from daily levels in mid-January, when omicron first emerged as the country’s dominant strain.
The Health Ministry said about 44% of the country’s intensive care units designated for COVID-19 patients are occupied.
health authorities anticipate the omicron wave will peak sometime in mid-March, when the country may see daily cases of around 250,000. There are concerns that transmissions could worsen with schools beginning new semesters in March and also because of political rallies ahead of the March 9 presidential election.
https://abcnews.go.com/Health/wireStory/korea-deadliest-day-pandemic-amid-omicron-surge-83124498
OSLO, Norway– 25 February 2022: The Coalition for Epidemic Preparedness Innovations (CEPI) today welcomed the Government of Japan’s a generous pledge of US$300 million CEPI’s ambitious global plan to reduce the risk of future pandemics and epidemics. The pledge reaffirms the Government of Japan’s commitment to CEPI and the principle of equitable access to vaccines as a cornerstone of global health security.
CEPI’s plan will reduce the risk posed by epidemics and pandemics by developing vaccines for known disease threats (such as Lassa fever, MERS and Nipah virus), and build on the scientific advances made during COVID-19 to prepare in advance for ‘Disease X’- an unknown pathogen with pandemic potential.
This investment comes at a critical time as the global community strives to end the acute phase of the COVID-19 pandemic and ensure that the world is better prepared to respond to future viral threats. The funding committed by Japan will also bolster CEPI’s work to develop the next generation of COVID-19 vaccines, including ‘variant-proof’ COVID-19 vaccines, as well as vaccines that provide broad protection against all Betacoronaviruses.
https://cepi.net/news_cepi/japan-pledges-us300-million-to-cepis-pandemic-preparedness-plan/
Today’s pledge from Japan comes ahead of the Global Pandemic Preparedness Summit on 7 and 8 March. Co-hosted with the UK Government the Summit aims to raise critical funds towards CEPI’s US$3.5 billion five-year plan to deliver?innovative, access-focused?R&D programmes and accelerate the development of safe, effective, and globally accessible vaccines against emerging diseases to as little as 100 days.
The Summit will bring together world leaders from government, industry, philanthropy, academia and civil society to explore how to achieve this ambitious goal, endorsed by the G7 and G20 and termed the 100 Days Mission.
2/25/22 Wes Howl: I just got unblinded: I got the vaccine, not the placebo, during my Inovio INO-4800 phase 2-3 clinical trial.
And were you Covid free for the entire time after the INO-4800 vaccine?
Covid free, before and after vaccination.
https://twitter.com/weshowl/status/1497284819662815241?s=21
Omicron BA.2 subvariant is more contagious and can reinfect people, but isn’t more severe, studies find
PUBLISHED FRI, FEB 25 2022
Danish scientists confirmed this week that the new subvariant can reinfect people who’ve previously had omicron, although it doesn’t appear to be all that common.
They also agree that it’s more contagious than the original version of omicron, BA.1, which is still widely circulating around the world.
But it’s surprisingly not driving a second wave of omicron infections. Globally, Covid cases have plunged 21% over the past week.
A more contagious subvariant of omicron, known as BA.2, is spreading across the globe and could soon become the dominant version of Covid-19.
It’s now the top variant in at least 18 countries and rapidly spreading, representing 35% of all new cases that have been genetically sequenced worldwide, up from 10 countries and 21% of cases the week before, according to new data from the World Health Organization. In the U.S, BA.2 currently makes up 3.8% of genetically sequenced Covid cases, according to the Centers for Disease Control and Prevention.
A pandemic-weary public wants to know two main things: Will BA.2 cause a second surge of omicron cases, and will it put even more people in the hospital with severe infections? So far, scientists say the answer to both questions is probably no.
However, Danish scientists confirmed this week that the new subvariant can reinfect people who’ve previously had omicron, although it doesn’t appear to be all that common. They also agree that it’s more contagious than the original version of omicron, BA.1, which is still widely circulating around the world.
But it’s surprisingly not driving a second wave of omicron infections. Globally, Covid cases have plunged 21% over the past week — subsiding in every region except the Western Pacific — while deaths have fallen 8% over the past week, according to data from the WHO.
Maria Van Kerkhove, the WHO’s Covid-19 technical lead, said the global health agency is closely monitoring countries that have detected BA.2, but so far the subvariant hasn’t caused a fresh surge in cases.
“As we’re seeing that decline in cases in countries, we’re not seeing an increase again with BA.2,” Van Kerkhove said during a question-and-answer session livestreamed on the WHO’s social media platforms Tuesday.
Here’s what’s known about the subvariant so far.
More transmissible
Danish researchers have found that BA.2 is about 30% more transmissible than BA.1. Denmark was one of the first countries where BA.2 became dominant, and public health authorities around the world have paid close attention to the situation there to gather insight on what the subvariant might mean for the future course of the pandemic.
“We conclude that Omicron BA.2 is inherently substantially more transmissible than BA.1,” a team of scientists affiliated with Danish public health authorities and the University of Copenhagen wrote in a study last month, which has not yet been peer-reviewed.
The U.K. Health Security Agency found in late January that BA.2 had a substantial advantage over BA.1 in England. “We now know that BA.2 has an increased growth rate which can be seen in all regions in England,” said Dr. Susan Hopkins, the agency’s chief medical advisor.
“If what is being reported is true that BA.2 is slightly more transmissible, then my strong inclination is to say that BA.2 will likely take over wherever BA.1 was,” said Mehul Suthar, a virologist at Emory University.
However, Suthar said this doesn’t necessarily mean that BA.2 will cause a surge of infection. BA.2's ability to cause another wave depends, in part, on whether it can reinfect people who have already caught and recovered from omicron, he said.
Reinfection possible, but appears rare
Danish scientists confirmed Tuesday that the BA.2 subvariant can reinfect people who previously had its omicron predecessor, BA.1, though the risk of catching the virus again appears low.
The Statens Serum Institute in Copenhagen analyzed a randomly selected sample of 263 reinfection cases. Forty-seven people caught BA.2 less than two months after infection with BA.1, according to the study. The majority of the people reinfected with BA.2 after BA.1 were younger than 20 years old and unvaccinated.
“The reinfection rate appears to be low given the high number of positive SARS-CoV-2 tests during the study period but still highlights the need for continuous assessment of length of vaccine-induced and/or natural immunity,” the study’s authors wrote.
The people reinfected had mild symptoms and none of them were hospitalized or died. The study also found that people reinfected with a BA.2 infection had a reduced viral load, indicating some crossover immunity from the first infection.
The U.K. Health Security Agency, in a separate study, found 69 cases of people reinfected with BA.2 no more than 90 days after their first infection with Covid. However, no instances of people reinfected by BA.2 after first catching BA.1 were found among the 51 cases where enough information was available. The timing of the first infections and sequencing indicated their original Covid cases were the delta variant.
Neither study has been peer-reviewed, which is the gold standard in academic publishing. Scientists have been publishing their research as quickly as possible due to the urgency of the pandemic.
On October 28, 2021, MedImmune Limited (“MedImmune”), the global biologics research and development arm of AstraZeneca, provided notice to Inovio Pharmaceuticals, Inc. (the “Company”) to terminate the INO-3112 / MEDI0457 development program under that certain DNA Cancer Vaccine Collaboration Agreement, dated August 7, 2015, by and between the Company and MedImmune (the “Collaboration Agreement”). As a result of the termination, the Collaboration Agreement has been terminated in its entirety. Under the Collaboration Agreement, MedImmune acquired exclusive rights to the Company’s INO-3112 immunotherapy, renamed as MEDI0457, which targets cancers caused by human papillomavirus types 16 and 18, with the ability to sublicense those license rights. The Collaboration Agreement permitted MedImmune to terminate the agreement at any time on a program-by- program, product-by-product and/or country-by-country basis. Following the termination of the Collaboration Agreement, the Company will reacquire the rights to INO-3112 and will no longer be entitled to receive potential future milestone payments or royalties under the Collaboration Agreement. The Company will also cease any development activities for which it would be entitled to seek reimbursement from MedImmune. The parties will continue to have rights to jointly publish work relating to the product candidate.
MedImmune is currently conducting a Phase 2 clinical trial of MEDI0457 in patients with head and neck squamous cell carcinomas (HNSCC). MedImmune has completed the final data cut off for the trial and plans to complete the clinical study report by the end of 2022. The Company expects that MedImmune will continue to sponsor this study until study termination. MedImmune will also continue providing financial support for an externally sponsored research study of MEDI0457 with The University of Texas MD Anderson Cancer Center until study completion.
The Company is no longer substantially dependent on the Collaboration Agreement. During the six months ended June 30, 2021 and the years ended December 31, 2020 and 2019, the Company recognized a total of $33,000, $171,000 and $2.0 million, respectively, in revenue under the Collaboration Agreement.
Advaccine finished heterologous and homologous booster recruiting. 4-wk Interim readout in Mar 2022. It could get China approval as booster.
China approves CanSinoBIO's Convidecia as heterologous booster for COVID-19
21 February 2022
For the Omicron variant, Convidecia generates neutralising antibody levels 6 times and 3 times higher than the groups given inactivated vaccines and recombinant protein vaccines, respectively.
CanSino Biologics Inc. has announced that its Recombinant Novel Coronavirus Vaccine (Adenovirus Type 5 Vector) (Convidecia) has been approved by the Joint Prevention and Control Mechanism of the State Council of China as a heterologous booster, making it the first adenovirus-vectored vaccine to be included in the heterologous vaccination programme in China.
According to the State Council, for those aged 18 and above who have completed a 6-month vaccination schedule using inactivated COVID-19 vaccines, and those who have not been administered a homologous booster, being administered CanSinoBIO's Convidecia as a heterologous booster can significantly increase the neutralizing antibody levels with proven safety.
Heterologous booster vaccination refers to the use of vaccine boosters from different technology platforms from the prime vaccines, which could improve the overall immune response and enhance protection against other variants.
In addition, administering Convidecia as a booster can also induce a significant CD8+T cellular immune response, which could rapidly kill virus-infected cells and reduce the chance of severe illness and death, providing both humoral and cellular immunity.
https://www.chictr.org.cn/hvshowproject.aspx?id=119337
Primary objective: ? To evaluate the humoral immunogenicity in healthy subjects (have received 2 doses of approved COVID19 inactivated vaccines previously) over 18 years old after boosted with the heterologous COVID-19 DNA vaccine. ? To evaluate the safety of the healthy subjects (have received 2 doses of approved COVID19 inactivated vaccines previously) over 18 years old after boosted with the heterologous COVID-19 DNA vaccine.
Secondary objective: ? To evaluate the cellular immunogenicity in healthy subjects (have received 2 doses of approved COVID19 inactivated vaccine) over 18 years old after boosted with the heterologous COVID-19 DNA vaccine.
Exploratory objective: ? To evaluate the long-term immune-response during follow-up in healthy subjects (have received 2 doses of approved COVID19 inactivated vaccine) over 18 years old after boosted with the heterologous COVID-19 DNA vaccine.
To evaluate the neutralizing response against COVID-19 variants in healthy subjects (have received 2 doses of approved COVID19 inactivated vaccine) over 18 years old after boosted with the heterologous COVID-19 DNA vaccine.
Inclusion Criteria:
The subjects in Cohort A have received two doses of the COVID-19 inactivated vaccine (approved) within 3 months (+15 days) and have been dosed at a time interval of 21 (+10) days between the first and second vaccination before participating in the screening of this study.
The subjects in Cohort B have received two doses of the COVID-19 inactivated vaccine (approved) within 6 months (+15 days) and have been dosed at a time interval of 21 (+10) days between the first and second vaccination before participating in the screening of this study.
2/24/22 Seeing this on Reddit reports that Inovio has "unblinded" all Phase 2 INO-4800 Trial subjects TODAY!. Press release could be happening as early as COB on success of INO-4800 vs Omicron. Reports are that Trial subjects gave blood during Omicrosn Surge and 1 year old status of the INO vaccinated would report its ability to deter Omicron vs Moderna and Pfizer (which require 6 month boosters).
2/24/22 Moderna says Covid is entering an endemic phase, but annual vaccines necessary
“We do believe that we are transitioning into an endemic phase marked by a period of stability in case counts, hospitalizations and deaths at least in the Northern Hemisphere,” Moderna Chief Medical Officer Paul Burton told analysts during a call Thursday morning after the company reported fourth-quarter earnings.
North America, Europe, most of Asia and much of Africa are in the Northern Hemisphere. However, Burton said Moderna is closely monitoring the trajectory of the virus in the Southern Hemisphere, which includes large nations such as Brazil and South Africa, as winter approaches there.
Moderna CEO Stephane Bancel told CNBC on Thursday that although Covid is entering an endemic phase in some parts of the world, people will need another booster shot in the fall. This is particularly true for individuals over 50 and those who are at high risk due to underlying health conditions, he said.
“I got a flu shot every year, not that I was worried of dying or getting hospitalized — I just don’t want to get sick,” Bancel said. On Thursday’s earnings call, Bancel said he expects Covid shots will have a similar role in the future as the virus becomes seasonal.
“Some countries like the U.K. and others wanted to secure supply because they believe very deeply that the endemic market will require annual boosters,” Bancel said.
Moderna on Thursday announced that it is developing a booster vaccine that targets omicron and other Covid variants such as delta. Burton said the current booster protects against hospitalization from delta and to a lesser extent from omicron. However, he said the effectiveness of the vaccine declines over time.
“We do see waning of protection over time against hospitalization due to infection, and this fits with the profound immune evasion we know to be the case with omicron,” Burton said. Due to waning immunity, a booster that targets both the omicron and delta variants will be needed in 2022, he said.
“This is because delta, as we know, is associated with strong pathogenicity, and omicron as we have seen due to its transmissibility and infectivity is also associated with substantial morbidity and strain on health-care systems through sheer bulk of cases,” Burton said. “Protection against both delta and omicron may well be necessary in the next boost of vaccination.”
Burton said the disease burden and deaths have declined from their highest levels during the first wave of infection, when no one had immunity to the virus.
“With each subsequent wave in mid-2021 with delta and late 2021 and early 2022 with omicron, the morbidity observed from these waves tended to be less severe, certainly relative to the first wave, as our immune systems became more experienced at fighting the SARS-CoV-2-virus,” Burton said.
In the U.S., Covid cases have fallen 90% from their peak level during the omicron wave on Jan. 15. The U.S. is reporting a seven-day average of about 80,000 new cases per day, according to data compiled by Johns Hopkins University, roughly one-tenth of the pandemic record of more than 800,000 average daily cases.
Hospitalizations have also fallen sharply to about 60,000 patients with Covid in U.S. hospitals from a high mark of more than 159,000 on Jan. 20, based on a seven-day average of data from the Department of Health and Human Services.
Worldwide, Covid cases are down 21% and new deaths have fallen 8% over the previous week, according to data from the World Health Organization. Infections are dropping in every region except the Western Pacific. However, new infections remain high, with 12 million reported for the week ended Feb. 20. More than 67,000 people died from Covid worldwide during that week alone.