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The selection of candidate vaccines for the STV involves evaluation of pre-defined criteria, including:
their safety and proven potential for effectiveness
stability of the vaccine
demonstration that they can be stored and transported easily under normal conditions
availability - whether they can be produced quickly for global distribution
the ease with which they can be given to individuals (how the vaccines are given, the number of doses etc)
To date the independent vaccine prioritization advisory group has reviewed the evidence generated on approximately 20 candidate vaccines. Of these, two candidate vaccines have been approved for inclusion in the STV. These are a spike adjuvanted vaccine developed by Medigen, and a DNA vaccine encoding the spike protein developed by Inovio.
https://www.who.int/emergencies/diseases/novel-coronavirus-2019/global-research-on-novel-coronavirus-2019-ncov/solidarity-trial-of-covid-19-vaccines
https://cdn.who.int/media/docs/default-source/blue-print/new2_solidarity-trial-vaccines-(stv)-presentation-4_final.pdf?sfvrsn=276fb250_18
Peruse Slide 26 of 44:
What ‘follow-up’ happens after the vaccines/
interventions are given?
Overview of the protocol visits and procedures
Main and secondary endpoints
Exploratory endpoints only
Visit number
1
2
3
4
5
6
7
Visit description
Vaccination dose 1
Follow-up visit days post-dose 1
Vaccination dose 2
Follow-up visit 7 days post-dose 2
Safety phone calls
Follow-up visit 180 days post-last dose
Follow-up visit 365 days post-last dose
Visit window (days)
Day 1
Day +7 (6-8) Post-dose 1
As per vaccine schedule
Day +7 (6-8) Post-dose 2
Day +7
(6-8) Post-previous contact – call
Day +180 (170-190 days) Post-last dose
Day +365 (350-380 days) Post-last dose
10/26/21 WHO and the Ministries of Health of Colombia, Mali, and the Philippines announce the launch of the co-sponsored Solidarity Trial Vaccines.
This is an international, randomized clinical trial platform designed to rapidly evaluate the efficacy and safety of promising new candidate vaccines selected by an independent vaccine prioritization advisory group composed of leading scientists and experts.
This announcement comes after the relevant regulatory authorities and ethics committees have granted approval for the study to progress.
The national principal investigators and their research teams in Colombia, Mali, and the Philippines have begun recruiting volunteers joining the trial.
The Solidarity Trial Vaccines is beginning with research teams in over 40 trial sites spread across the three countries. National research teams bring together experienced investigators well-versed in good clinical practice and the conduct of clinical trials.
To date, the independent vaccine prioritization advisory group has reviewed the evidence of around 20 candidate vaccines. Following the recommendation of the working group, 2 candidate vaccines are now included in the Solidarity Trial Vaccines. These are a protein subunit vaccine from Medigen, and a DNA vaccine encoding the spike protein from Inovio.
Two additional vaccines are expected to enter the Solidarity Trial Vaccines once additional evidence and documentation has been reviewed and accepted as satisfactory by the independent vaccine prioritization advisory group.
It is expected that other candidate vaccines currently under consideration by the vaccine prioritization advisory group may be added to the trial in late 2021 and during 2022.
The Solidarity Trial Vaccines aims to accelerate the evaluation of multiple promising candidate COVID-19 vaccines, contributing to the creation of a larger portfolio of vaccines needed to protect people from COVID-19 around the world. The trial has the additional potential to uncover second-generation vaccines with greater efficacy, conferring greater protection against variants of concern, offering longer duration of protection, and/or using needle-free routes of administration.
Acknowledgments
The WHO together with the Ministries of Health and Governments of Colombia, Mali and the Philippines are co-sponsoring the trial. Other countries will join the trial in coming weeks.
Participating vaccine developers are donating the candidate vaccine used in the trial and technical support including training for local teams.
The trial protocol and SOPs benefited from deliberations and inputs from hundreds of global experts participating in various WHO’s COVID-19 research and innovation collaborative platform [1].
The trial implementation benefits from the technical expertise of a global trial team composed of at least 50 international scientists and researchers from academia, research institutes, private sector and developing country research organizations. Under the auspices of this R&D Blueprint, the global team is providing the backbone end-to-end support to the Principal Investigators in each country on the resourcing, operationalization, and monitoring of the trial.
WHO would like to further acknowledge the support of numerous organizations dedicated to the success of the Solidarity Trial Vaccines. The trial includes a partnership with Johnson & Johnson to implement the Vaccination Monitoring Platform – a digital tool that aims at improved participant identification and tracing, data management and two-way communication with participants to implement impactful clinical trials.
Critical support is being provided by the Bern University (CTU), Bernhard Nocht Institute for Tropical Medicine, Castor EDC, Colsánitas, Colombia, Center for Vaccine Development Mali, Oxford University, University of Florida, University of Liverpool, University of the Philippines, and the University of Washington. Numerous other partners are supporting the trial teams via contractual arrangements with WHO.
Funding
The countries WHO would like to thank the German Government (BMG) and the Solidarity Response Fund for their flexible financial contributions towards this initiative.
Omicron surge must have helped INNOVATE and the WHO’s SVT in Jan 2022. The reopening had been set for Dec. 1 but was postponed as the highly contagious omicron variant of the coronavirus spread.
Less than a thousand new cases were added daily during the Christmas holidays, when large crowds of shoppers trooped back to malls and restaurants despite constant government warnings. The subsequent surge peaked above 39,000 infections in a day in mid-January, but has since eased. Health officials reported about 3,600 infections on Wednesday, with 69 deaths and have declared the entire archipelago, except for one southern region, at “low to moderate risk.”
More than 60 million of nearly 110 million Filipinos have been fully vaccinated against the coronavirus and 8.2 million have received their booster shots in a campaign that has been hampered by vaccine shortages and public hesitancy.
https://www.google.com/amp/s/www.wiltonbulletin.com/news/amp/Philippines-welcomes-back-foreign-travelers-after-16846453.php
The agreement calls for Advaccine — a Chinese biotechnology company that specializes in vaccine development — to make an upfront payment of $3 million to Inovio (NASDAQ: INO), and up to another $108 million in potential payments based on achieving undisclosed development and sales-based milestones for INO-4800 in Greater China.
Plymouth Meeting-based Inovio will be entitled to receive a royalty equal to a high single-digit percentage of annual net sales in each region within Greater China.
“Inovio’s partnership with Advaccine enables us to leverage their deep expertise, capabilities and network across the region – making it possible to rapidly produce and if and when approved, distribute our vaccine candidate to more people across Greater China," said J. Joseph Kim, Inovio's CEO. "This agreement also provides Inovio with an Asian manufacturing partner with a near-term focus on INO-4800 and a long-term manufacturing resource potentially for other Inovio products.”
Dr. Bin Wang, founder and chairman of Advaccine, said his company's manufacturing facility in Suzhou has the capacity to produce more than 100 million doses of DNA vaccine per year.
"Given the strong safety profile and robust immune responses observed in the U.S. and China clinical trials of INO-4800, we are confident in the vaccine candidate and are fully committed to the manufacturing of INO-4800 for Greater China," Wang said in a statement. 1/4/21
https://www.bizjournals.com/philadelphia/news/2021/01/04/inovio-covid-19-vaccine-license-china-advaccine.html
Inovio's vaccine candidate differs from some of the other Covid-19 vaccines approved or in development in that it does not need to be frozen during transport or storage and is projected to be stable at room temperature for over a year, with a five-year projected shelf life at normal refrigeration temperature.
“In fact, we think VGX-3100 (HPV program) and INO-5401 (GBM program) will be the main value drivers for Inovio moving forward, and while we don’t expect any catalysts for these programs in 1H22, we expect readouts for INO-4500 in Lassa fever and INO-3107 in RRP in 1H22 to further de-risk the platform and add momentum to the story,” he added.
1/21/22 BofA analyst Geoff Meacham upgraded Inovio to Neutral from Underperform with a price target of $10, up from $8. The analyst cites the stock's recent weakness and contends that the majority of remaining COVID-19 value has been removed from valuation following the recent 18% year-to-date pullback. Meacham adds that Inovio's commercial outlook for its COVID-19 vaccine has not changed, and the data generated from the program has demonstrated a favorable safety-profile and robust efficacy.
https://markets.businessinsider.com/news/stocks/why-this-analyst-has-increased-confidence-in-inovio-pharmaceuticals-1031119562
https://thefly.com/news.php?symbol=INO
Apr 20 09:00
Chair’s opening remarks
Emerging and Infectious Diseases
David Weiner,VP, Director of Vaccine & Immunology Center, The Wistar Institute
Apr 21 09:00
Chair’s opening remarks
Emerging and Infectious Diseases
Stanley Plotkin,Emeritus Professor, University of Pennsylvania School Of Medicine
Apr 21 09:40
Inovio’s DNA COVID vaccine update
COVID & Beyond
Joseph Kim,Chief Executive Officer, Inovio Pharmaceuticals
World Vaccine Congress 2022
WASHINGTON DC, 18 - 21 APRIL 2022
https://www.terrapinn.com/conference/world-vaccine-congress-washington/agenda.stm?utm_source=email&utm_medium=pardot&utm_campaign=UK_10550_WVC+DC+2022_CONFPROM&utm_term=email
Version 2, 1/25/22 This report provides results for the expansion of a Phase 1 trial to include older and elderly participants and an optional booster dose with the aim to evaluate the safety, tolerability, and immunogenicity of INO-4800, a SARS-CoV-2 vaccine encoding the S protein[14], including the immune responses 6 months following dose 2 and 2 weeks following the optional booster dose.
INO-4800 appeared to be well-tolerated at all three dose levels, with no treatment-related serious adverse events (SAEs) reported. Most AEs were mild in severity and did not increase in frequency with age and subsequent dosing. These results are consistent with the severity of AEs and lack of treatment-related SAEs observed in the U.S. Phase 2 trial comparing the 1.0 mg and 2.0 mg doses of INO-4800 in approximately 400 subjects[15] and those studies conducted outside the U.S. by Inovio collaborators (International Vaccine Institute, Advaccine – manuscripts in preparation). The lower frequency of treatment-related AEs reported by older and elderly participants in our study is consistent with findings of other studies evaluating SARS-CoV-2 vaccines[19, 20]. Weaker inflammatory reactions consequent to immunosenescence may explain the lower incidence of AEs among elderly participants[21, 22].
Induction of both humoral and cellular responses were observed across all three dose groups, inclusive of binding and neutralizing antibodies and cytokine producing T cells as well as exhibiting lytic potential. Immunization with the 2.0 mg dose resulted in the highest GMTs of neutralizing and binding antibodies as well as the highest magnitudes of IFN? production to SARS-CoV-2 of any dose in all age groups tested, and the increases in antibody levels were statistically significant above baseline at 6 months following dose 2. Importantly, increases in both humoral and cellular immune responses were statistically significant following the booster dose.
The contribution of the CD8+T cell response to vaccine efficacy has become increasingly recognized as they have been detected early after vaccination[23] and due to their role in controlling infection[24, 25]. Specifically, it has been established that CD8+T cells expressing cytokines such as IFN? and TNFa as well as markers involved in activation status and proliferation such as CD38 and Ki67 contribute to limiting disease severity during SARS-CoV-2 infection[24]. Additional studies have identified the expression of CD69 and CD137 on SARS-CoV-2 specific CD8+T cells being associated with less severe disease[25]. This expanded Phase 1 trial demonstrates that immunization with INO-4800 induces SARS-CoV-2 specific CD8+T cells exhibiting these specific characteristics, suggesting the induction of a vaccine-induced cellular response that has potential to protect against severe COVID-19. As VoCs continue to emerge, the generation of cross-reactive activated CD8+T cells with lytic potential is likely to play an important role in preventing severe disease. We have previously demonstrated that vaccination with INO-4800 induces T cells and neutralizing antibodies that are active against the parental SARS-CoV-2 strain as well as the B.1.1.7, B.1.351, and P.1 VoCs[26].
This trial demonstrated that immune responses elicited by a 2-dose primary series of INO-4800 could be boosted by a third dose without safety or tolerability concerns and positions INO-4800 as an important candidate for continued development as a stand-alone SARS-CoV-2 vaccine, as well as for continued examination in combination approaches. The potential ability to administer INO-4800 multiple times, with high tolerability, along with its ease of scalability and thermostability, contribute to its potential value in combatting the COVID-19 pandemic.
https://www.medrxiv.org/content/10.1101/2021.10.06.21264584v2.full
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.
https://ir.inovio.com/news-releases/news-releases-details/2021/INOVIO-Highlights-Key-Updates-on-Phase-3-Program-for-VGX-3100-its-DNA-based-Immunotherapy-for-the-Treatment-of-Cervical-HSIL-Caused-by-HPV-16-andor-HPV-18/default.aspx
2/8/22 A: “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 trials are progressing.”
2/8/22 Q: When Will Advaccine go IPO in HK exchange this year? Will heterologous trial draw blood 2, 4, 6, 8, … in increment of 2 weeks after the booster shot?
Do you have link to homologous study?
Note: Link to heterologous booster trial updated 12/7/21
Study execute time:
From2021-12-25 To 2022-07-25
6 groups of 80 ppl each
Cohorts A have received 2 Coronavac doses within 3 mos prior.
Cohorts B have received 2 Coronavac doses within 6 mos prior.
Each cohort receives 0.5, 1, 2 mg 4800/pGX9501 or placebo
https://www.chictr.org.cn/hvshowproject.aspx?id=119337
"Trying to stop omicron is kind of like trying to stop the wind," he told CNBC's "Squawk Box Asia."
China is "uniquely at risk" to omicron, Osterholm said, for a combination of reasons: Early studies suggest its Sinovac and Sinopharm vaccines are "not very effective" against the variant, and at the same time China's success at preventing the spread of Covid so far means it has a very large population that remains vulnerable.
According to U.S.-based consultancy Eurasia Group, China's zero-Covid policy ranks among the top risks for 2022.
While the approach "looked incredibly successful in 2020," it has now "become a fight against a much more transmissible variant with broader lockdowns and vaccines with limited effectiveness,"
https://news.google.com/articles/CAIiEFfonXmF9eDW6sbyARYHIw0qGQgEKhAIACoHCAow2Nb3CjDivdcCMJ_d7gU?hl=en-US&gl=US&ceid=US%3Aen
1/30/22 In 2020, one of the big hurdles the frontrunner vaccines had to face was managing to have enough trial participants ready and waiting in just the places that outbreaks would roll over them – something that required both good management and luck. Setting up trials takes a lot of time, and you couldn’t predict where the lightning was going to strike. I wrote about that challenge at WIRED.
Now there’s no shortage of outbreaks, unfortunately, but there’s another issue: how do you get enough unvaccinated people to run a big phase 3 trial when pretty much everyone who is both easy enough to reach and wants to be vaccinated already is vaccinated? Here’s hoping that there have been conversations with the WHO SOLIDARITY trial for vaccines about this.
That’s a big phase 3 trial with a shared placebo group to test 4 easy-to-distribute and scale up vaccines. As of the middle of December, 5,000 people had already been recruited in the Philippines alone. There are 2 vaccines already in the trial – a protein subunit vaccine from Medigen (Taiwan) and a DNA vaccine from Inovio (USA). The next 2 candidates are the self-amplifying RNA vaccine from Arcturus (USA) and a live attenuated vaccine from Codagenix (USA – to be manufactured by the Serum Institute of India). More vaccines could be added, though.
https://absolutelymaybe.plos.org/2022/01/30/new-triumphs-struggles-for-non-profit-covid-vaxes/
“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,” DOST Undersecretary for Research and Development Dr. Rowena Cristina L. Guevara 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 [40K worldwide in Mali, Colombia] 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/
Moderna fails to make a difference or an improvement on Omicron specific vaccine. The game is afoot. It really does come back full circle to the T cells.
"Therefore, an Omicron boost may not provide greater immunity or protection compared to a boost with the current mRNA-1273 vaccine."
https://www.biorxiv.org/content/10.1101/2022.02.03.479037v1
Primary sponsor:
Sichuan Provincial Center for Disease Control and Prevention
6 Zhongxue Road, Chengdu, Sichuan, China
Province:
Sichuan
City:
Neijiang
hospital:
Neijiang City Center for Disease Control and Prevention
pGX9501 is hand picked, endorsed by the powerful CCP as they know Sinovac’s Coronavac is not efficacious. No other foreign vaccine is allowed trial there. CCP needs a back up plan in pGX9501 for its own ppl and Vaccine Diplomacy. I have no qualm about that as I know it’s the safest, probably the best CD4+, CD8+, longest immunity duration, no cold chain required vaccine available. CCP wants to project an image of superpower superiority with a superior vaccine thanks to Faucci, FDA, DoD mRNA favoritism and greed.
I have to spell out the political, scientific ramifications as few longs see this huge advantage while shorts try to kill Ino. I don’t mind if state-sponsored Sinovac acquires Advaccine to ensure DNA success.
https://www.chictr.org.cn/hvshowproject.aspx?id=119337
2/3/22 Biden Praises Doctor for 'Trying to Save' Son Beau as First Family Opens Up at 'Cancer Moonshot' Kickoff
The Biden administration is reigniting an effort to reduce deaths from cancer and change the lives of those dealing with a diagnosis
https://people.com/politics/bidens-vice-president-share-personal-agony-and-hope-at-cancer-moonshot-event/
Biden's relaunched cancer moonshot needs funding for liftoff
The new moonshot lands one year into Biden’s presidency, giving the administration a long runaway to steer its progress.
https://www.politico.com/news/2022/02/03/biden-relaunched-cancer-moonshot-funding-00005042
Go GBM INO-5401 !
There are 2 trials, heterologous and homologous.
The heterologous finished recruiting before Lunar New Year (Feb 1) and Beijing Winter Olympic (Feb 3). ppl starts leaving for 2-wk vacation between Fri 1/2–1/31. 4 wks after 1/28, blood test begins. Interim data should be available early March. Things move much faster in China. Together with WHO’s STV data from Philippines - WHO moves fast as well as you saw news from Manila Bulletin early Jan 2022 - 4800 is progressing well. Coronavac desperately needs 4800 booster as Sinovac’s is not effective. Huge China and worldwide market as China donates/sells Coronavac oversea, Vaccine Diplomacy. It’s the most popular vaccine outside China as well.
Officially, China only allows vaccine made in China To be used in China. Therefore, 4800/pGX9501 has a huge advantage. Pfizer, Moderna have zero chance in China. China will push pGX9501 in Vaccine Diplomacy as well at least as Booster. This should take market share from other Vaccines.
Latest update on China 4800/pGX9501 heterologous booster trial with new link
6 groups, 80 ppl each
Registration number:
ChiCTR2100049744
??????:
Date of Last Refreshed on:
2021/12/7 4:27:15
Study execute time:
?From2021-12-25?To 2022-07-25
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.
https://www.chictr.org.cn/hvshowproject.aspx?id=119337
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.
Federal agents raided home of short-seller Andrew Left in 2021: report
By Ariel Zilber
February 4, 2022 2:52pm
https://nypost.com/2022/02/04/federal-agents-raided-home-of-andrew-left-in-2021-report/
High CV attack rate in Mexico, Colombia, Philippines helps expedite INNOVATE and the WHO’s STV
2/5/22 Positive rate per country
Average of the positive rate of the last two weeks.
Country
Average (%)
Positive rate
Mexico
66.5
Argentina
64.2
Colombia
41
Philippines
39.6
https://interactive.news.sky.com/2020/covid-19-coronavirus/world-positive-country-rate-table/index.html
https://www.beckershospitalreview.com/public-health/states-ranked-by-covid-19-test-positivity-rates-july-14.html
Datapoints were last updated on Saturday, February 5, 2022 at 06:01 AM EST.
Kansas: 100.0%
New Daily Cases: 4871
Tests per 100k: 99.8
Colorado: 87.0%
New Daily Cases: 3695
Tests per 100k: 77.0
Idaho: 86.1%
New Daily Cases: 2428
Tests per 100k: 100.0
Pennsylvania: 75.7%
New Daily Cases: 7091
Tests per 100k: 84.2
Nevada: 61.6%
New Daily Cases: 2104
Tests per 100k: 121.1
Oklahoma: 50.9%
New Daily Cases: 4742
Tests per 100k: 498.0
New Jersey: 49.8%
New Daily Cases: 3023
Tests per 100k: 66.1
Wisconsin: 39.0%
New Daily Cases: 4008
Tests per 100k: 181.3
Tennessee: 37.3%
New Daily Cases: 11275
Tests per 100k: 448.5
Arkansas: 30.1%
New Daily Cases: 1507
Tests per 100k: 248.9
Alabama: 29.0%
New Daily Cases: 11196
Tests per 100k: 322.2
Alaska: 29.0%
New Daily Cases: 3835
Tests per 100k: 0.0
South Carolina: 28.6%
New Daily Cases: 6657
Tests per 100k: 1423.6
Iowa: 27.8%
New Daily Cases: 0
Tests per 100k: 331.8
South Dakota: 27.6%
New Daily Cases: 569
Tests per 100k: 222.6
Texas: 27.1%
New Daily Cases: 21769
Tests per 100k: 438.9
Utah: 26.6%
New Daily Cases: 2808
Tests per 100k: 414.5
Missouri: 25.6%
New Daily Cases: 2698
Tests per 100k: 303.8
New Hampshire: 25.3%
New Daily Cases: 1458
Tests per 100k: 369.1
Kentucky: 25.1%
New Daily Cases: 8352
Tests per 100k: 509.2
Florida: 23.9%
New Daily Cases: 131699
Tests per 100k: 553.9
North Carolina: 22.9%
New Daily Cases: 12385
Tests per 100k: 474.0
District of Columbia: 22.2%
New Daily Cases: 259
Tests per 100k: 160.3
Michigan: 20.9%
New Daily Cases: 12040
Tests per 100k: 353.4
Georgia: 20.8%
New Daily Cases: 8798
Tests per 100k: 373.6
Minnesota: 20.4%
New Daily Cases: 6610
Tests per 100k: 508.3
Virginia: 20.0%
New Daily Cases: 6500
Tests per 100k: 294.1
Washington: 20.0%
New Daily Cases: 12341
Tests per 100k: 0.0
Oregon: 19.5%
New Daily Cases: 4954
Tests per 100k: 745.4
New Mexico: 18.3%
New Daily Cases: 2097
Tests per 100k: 715.0
Indiana: 18.0%
New Daily Cases: 4312
Tests per 100k: 543.6
Ohio: 17.9%
New Daily Cases: 4004
Tests per 100k: 271.1
North Dakota: 17.6%
New Daily Cases: 1184
Tests per 100k: 514.3
Arizona: 17.2%
New Daily Cases: 9077
Tests per 100k: 734.5
Puerto Rico: 16.9%
New Daily Cases: 1533
Tests per 100k: 137.9
Mississippi: 15.9%
New Daily Cases: 7839
Tests per 100k: 367.8
West Virginia: 15.5%
New Daily Cases: 2911
Tests per 100k: 790.7
Delaware: 15.3%
New Daily Cases: 595
Tests per 100k: 567.0
Montana: 14.0%
New Daily Cases: 4423
Tests per 100k: 702.5
Maine: 13.1%
New Daily Cases: 1413
Tests per 100k: 607.6
Nebraska: 12.4%
New Daily Cases: 1098
Tests per 100k: 626.7
Hawaii: 11.8%
New Daily Cases: 1192
Tests per 100k: 803.7
Rhode Island: 11.3%
New Daily Cases: 860
Tests per 100k: 1003.4
Connecticut: 10.2%
New Daily Cases: 1269
Tests per 100k: 456.4
Louisiana: 10.2%
New Daily Cases: 6206
Tests per 100k: 545.4
Wyoming: 9.7%
New Daily Cases: 1460
Tests per 100k: 481.7
California: 8.4%
New Daily Cases: 37012
Tests per 100k: 1294.1
Vermont: 6.7%
New Daily Cases: 516
Tests per 100k: 1189.4
Maryland: 6.5%
New Daily Cases: 1604
Tests per 100k: 626.8
Massachusetts: 6.1%
New Daily Cases: 4758
Tests per 100k: 1158.9
Illinois: 5.8%
New Daily Cases: 18464
Tests per 100k: 1171.5
New York: 5.2%
New Daily Cases: 7759
Tests per 100k: 836.9
2/5/22 High attack rate in Philippines ???? helps expedite INNOVATE and the WHO’s STV
Most infections in Metro
https://newsinfo.inquirer.net/1550181/govt-sets-another-vax-drive-for-feb-10-11
Metro Manila was back on the list of regions which registered the most number of cases with 907, followed by Western Visayas with 782, and the Davao Region with 753.
The country’s positivity rate was 24.3 percent, lower than the 25.5 percent on Thursday. This was based on 37,932 people tested on Wednesday.
The national caseload was now 3,594,002. There were 151,389 active cases, of which 139,940 were mild; 6,522, asymptomatic; 3,107, moderate; 1,500, severe; and 320, critical.
The 10,474 new recoveries brought the total number of survivors to 3,388,399.
There were 46 new fatalities, which raised the death toll to 54,214. The DOH said 26 deaths were from this month, while the rest happened between October 2021 and January 2022 and were reported only on Friday.
Intensive care unit beds in Metro Manila were now 38-percent full (against 44 percent at the national level); isolation beds, 32 percent (42 percent nationwide); and ward beds, 35 percent (also 42 percent nationwide).
Friday’s bulletin said 21 percent of ventilators in Metro Manila were in use, against 22 percent for the whole country.
Pediatric cases
In an advisory, the DOH said that contribution of children between 0 and 11 years old to the total pediatric cases was higher during the Omicron wave last January compared with the Delta wave late last year.
“Cases among the 0 to 11 age group comprised an average of 56 percent of the total pediatric cases in September and this climbed up to 69.2 percent in January,” the department said.
The DOH reported 8,564 new coronavirus infections on Friday, the fourth straight day that the daily tally fell below 10,000.
Yet amid the decline in new cases, Dr. Guido David, fellow of independent pandemic monitor OCTA Research, said infections in 11 provinces continued to increase as manifested by their “positive” one-week growth rates.
These provinces are Bukidnon, Cotabato, Davao del Norte, Guimaras, Maguindanao, Sarangani, Siquijor, South Cotabato, Sultan Kudarat, Tawi-Tawi and Zamboanga del Norte.
He also noted “very high” growth rates in Davao Occidental (85 percent) and Camiguin (78 percent).
Still, the new cases in the latest DOH bulletin were slightly lower than Thursday’s 8,702, even as the tally did not include figures from six laboratories which failed to submit their data to the DOH.
2/4/22 Researchers discover HIV variant that's more contagious and more severe circulating in the Netherlands
https://news.google.com/articles/CAIiEGfO1QjRfHZTiYiJpgtSIaYqLQgEKiUIACIbd3d3LmJ1c2luZXNzaW5zaWRlci5jb20vc2FpKgQICjAMMJD-CQ?hl=en-US&gl=US&ceid=US%3Aen
Oppenheimer analyst mentioned Innovio in a very positive way several times and DNA vaccines at the very end of this video about Covid 19 vaccines in 2022.
Oppenheimer analyst Hartaj Singh joins Yahoo Finance's Brian Sozzi and Julie Hyman to predict what vaccine stocks Pfizer and Moderna will do in 2022.
Wistar Scientists Move HIV Vaccine Research Forward by Developing an Immunogen that Produces Tier-2 Antibodies—the Kind That Matter for Combatting HIV
Released: 3-Feb-2022 3:55 PM EST
Newswise — PHILADELPHIA — (Feb. 4, 2022) — Nearly four decades after its discovery, HIV has killed 36.3 million people, with no vaccine in sight. However, a new study by researchers at The Wistar Institute, an international biomedical research leader in cancer, immunology, infectious disease, and vaccine development, takes a promising step in the direction of developing an HIV vaccine.
The findings, published in Nature Communications, demonstrate the promise of using a unique native-like trimer to develop Tier-2 neutralizing antibodies—the kind that matter for combatting HIV—in mice for the first time.
Previously, eliciting these types of antibodies using candidate vaccines required long and expensive experiments in large animal models creating a significant bottleneck on HIV-1 vaccine development. “With our new finding, we have opened the door to rapid, iterative vaccinology in a model that can produce Tier-2 neutralizing antibodies, enabling development of more advanced HIV vaccine concepts,” said Daniel Kulp, Ph.D., associate professor in the Vaccine & Immunotherapy Center at The Wistar Institute and corresponding author on the paper.
The researchers encoded the native-like trimer into DNA for delivery into the mice. This has the practical advantage of turning the host bodies into “antigen factories” instead of requiring what would otherwise be a complex vaccine manufacturing process. The researchers then compared the results from the mice who received the DNA-encoded native-like trimer to results from mice who received a standard protein immunization. Only those mice that received the DNA-encoded native-like trimer developed Tier-2 neutralizing antibodies.
“We were able to generate strong immune responses with both platforms, but the DNA platform uniquely drove this neutralizing response,” said Kulp.
Once they’d verified their immunization regime was producing Tier-2 antibodies, Kulp and his colleagues isolated monoclonal antibodies from the mice and used cryo-electron microscopy to determine the atomic structure of one Tier-2 neutralizing monoclonal antibody. They found that the antibody binds to an epitope (a segment of a protein that sticks out of the antigen, which prompts an immune response) called C3V5. In the gold standard HIV vaccine model (non-human primates), prior research has shown that antibodies binding to C3V5 protect animals from a SHIV infection, which is a close relative of HIV that infects non-human primates.
“The structure gives us incredible insight into how this antibody is able to neutralize the virus,” said Kulp. “For the first time, we can strategize about how to design new vaccines that can generate broadly neutralizing antibody responses to the C3V5 epitope.”
Coauthor David B. Weiner, Ph.D., executive vice president and director of the Vaccine & Immunotherapy Center and the W.W. Smith Charitable Trust Professor in Cancer Research at The Wistar Institute, emphasized the utility of their findings.
“What we’ve done is enable direct in vivo self-assembly of structurally designed immunogens, which are engineered and delivered using nucleic acid technology, inside the vaccinated animal. Our data demonstrating induction of autologous Tier 2 neutralization illustrate the value of this approach as a tool to create surgically tailored immunity against a difficult pathogen’s vulnerable sites, in this case for HIV.”
Co-authors: Ziyang Xu, Susanne Walker, Neethu Chokkalingam, Mansi Purwar, Edgar Tello-Ruiz, Yuanhan Wu, Sonali Majumdar, Kylie M. Konrath, Abhijeet Kulkarni, Nicholas J. Tursi, Faraz I. Zaidi, Emma L. Reuschel, Ishaan Patel, April Obeirne, David B. Weiner, and Daniel W. Kulp from The Wistar Institute; Megan C. Wise, Katherine Schultheis, Lauren Gites, Trevor Smith, Janess Mendoza, Kate E. Broderick, and Laurent Humeau from Inovio Pharmaceuticals; Alan Moore, Jianqiu Du, and Jesper Pallesen from Indiana University.
Work supported by: National Health Institutes (NIH) IPCAVD Grant U19 Al109646-04; W. W. Smith Charitable Trust; and Wistar Monica H.M. Shander Memorial Fellowship.
Publication information: Induction of Tier-2 Neutralizing Antibodies in Mice with a DNA-encoded HIV Envelope Native Like Trimer, Nature Communications, 2022. Online publication.
2/4/22 Vast DOJ Probe Looks at Almost 30 Short-Selling Firms and Allies
FBI said to show up at home of Citron’s Left in early 2021
Subpoenas to some firms since have sought info on dozens more
https://news.bloomberglaw.com/securities-law/vast-doj-probe-looks-at-almost-30-short-selling-firms-and-allies
Big DOJ Probe Looks at Almost 30 Short-Selling Firms and Allies
What You Need to Know
As part of the probe, the Federal Bureau of Investigation seized computers from the home of Andrew Left, the founder of Citron Research, some sources said.
The Securities and Exchange Commission also has sent some requests for information.
The Justice Department and financial regulators have faced a growing number of calls in recent years to dig into short sellers and their research partners.
https://www.thinkadvisor.com/2022/02/04/big-doj-probe-looks-at-almost-30-short-selling-firms-and-allies/
Induction of tier-2 neutralizing antibodies in mice with a DNA-encoded HIV envelope native like trimer
Received
24 February 2021
Accepted
11 January 2022
Published
04 February 2022
https://www.nature.com/articles/s41467-022-28363-z
Abstract
HIV Envelope (Env) is the main vaccine target for induction of neutralizing antibodies. Stabilizing Env into native-like trimer (NLT) conformations is required for recombinant protein immunogens to induce autologous neutralizing antibodies(nAbs) against difficult to neutralize HIV strains (tier-2) in rabbits and non-human primates. Immunizations of mice with NLTs have generally failed to induce tier-2 nAbs. Here, we show that DNA-encoded NLTs fold properly in vivo and induce autologous tier-2 nAbs in mice. DNA-encoded NLTs also uniquely induce both CD4?+?and CD8?+?T-cell responses as compared to corresponding protein immunizations. Murine neutralizing antibodies are identified with an advanced sequencing technology. The structure of an Env-Ab (C05) complex, as determined by cryo-EM, identifies a previously undescribed neutralizing Env C3/V5 epitope. Beyond potential functional immunity gains, DNA vaccines permit in vivo folding of structured antigens and provide significant cost and speed advantages for enabling rapid evaluation of new HIV vaccines.
2/4/22 FBI Seized Computers From Short Seller Andrew Left, Others Subpoenaed in Vast Probe
FBI Seized Computers From Short Seller Andrew Left, Others Subpoenaed in Vast Probe
— *Walter Bloomberg (@DeItaone) February 4, 2022
INNOVATE trial in Rwanda, Tunisia
Pan African Clinical Trials Registry
https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=16121
CEPI opens Call to develop heat-stable vaccine tech for use against epidemic and pandemic threats
3 February 2022, Oslo, Norway – The Coalition for Epidemic Preparedness Innovations, CEPI, has launched a new Call for Proposals to improve the thermostability of vaccines against known epidemic and pandemic diseases—like Ebola, Lassa fever, MERS, as well as COVID-19—or a novel Disease X. The aim of the Call is to minimise the need for complex cold-chain requirements in order to improve global access to vaccines and, in turn, reduce potential vaccine wastage.
CEPI is particularly interested in hearing from vaccine developers and tech companies with new or existing innovations that could support the development of one or more infectious disease vaccines that are both heat-stable and freeze-stable. Example innovations that CEPI may look to fund include temperature-stable vaccine nasal sprays, microarray patches, or orally administered vaccines.
Technologies must be applicable to current or future vaccines and accessible to low- and middle-income countries, and the innovation should not affect other key vaccine criteria such as costs, capacity, and ease of use.
Up to $17.5 million will be made available to support the innovations, with the aim to fund 3 to 5 projects in 2022. This work is part of CEPI’s goal, as part of its $3.5bn pandemic preparedness plan, launched in March 2021, to harness innovative technologies to improve the speed, scale and access of vaccine development and manufacturing in response to epidemics and pandemics. The Call may be extended to include other innovation areas that contribute to this goal.
Interested groups could either apply individually or, for example if an independent tech institution, pair together with a vaccine manufacturer and apply as a consortium.
The need for thermostable vaccines
Vaccines are biological products which can lose their effectiveness when exposed to temperatures that are either too hot or too cold. Therefore, cold-chains—involving fridges, freezers, cool boxes for shipping, and other equipment—are used to enable vaccines to be kept at a particular temperature during shipment, storage, and delivery.
While advantageous for maintaining vaccine potency, such temperature requirements can make vaccines inaccessible to remote areas or low-resource settings lacking the infrastructure and technologies needed to store and distribute these vaccines at certain temperatures. This is true for the rollout of some of the currently approved COVID-19 vaccines, including Pfizer/BioNTech and Moderna mRNA-based COVID-19 vaccine technologies requiring ultra-cold temperatures of -20 °C to -80 °C.
Cold chain requirements are also one of the key reasons for vaccines being wasted globally, as vaccines end up discarded after they have potentially been exposed to heat or freezing.
The ability for vaccines to withstand heat exposure has therefore been identified as the most desired characteristic for vaccines used in outreach and campaign settings by experienced immunisation staff. Thermostable vaccines are also identified as a preferred vaccine characteristic by the World Health Organization (WHO).
Call details
The Call seeks to enable vaccine platforms that currently require freezing, like the RNA vaccine platforms being used in the COVID-19 response, to instead work at the already established cold chain (requiring refrigeration at 2-8°C). CEPI will also support innovations that aim to improve thermostability for any vaccine type to a preferred target of 40°C that allows the last stage of the supply chain to occur without cold chain equipment.
A full list of the epidemic and pandemic pathogens applicants could target is available online.
The new Call is now open for Expressions of Interest up until 31 December 2022. Successful applications may then be invited to submit full proposals for funding.
https://cepi.net/news_cepi/cepi-opens-call-to-develop-heat-stable-vaccine-tech-for-use-against-epidemic-and-pandemic-threats/
2/2/22 Could Inovio Pharmaceuticals Become the Next Moderna?
Key Points
Inovio's medicines use a scientific approach similar to Moderna's.
The company's coronavirus shot could help it to grow massively if it is approved.
Because Moderna has such a large lead, it's unlikely that Inovio could follow the same trajectory.
When it comes to biotechs, Moderna (NASDAQ:MRNA) is the standard to beat. With its market cap expanding sharply from near $5.3 billion in late 2019 to over $62 billion today, the stock has been a tremendous winner for its early investors. And that's why people are on the lookout for a repeat performance, perhaps from a very similar company called Inovio Pharmaceuticals (NASDAQ:INO).
On the surface, Inovio is very much in the same position that Moderna was before the pandemic. With a market cap close to $900 million, it doesn't have any recurring revenue or any medicines that are approved for sale, and its coronavirus vaccine program is what originally put it in the limelight in 2020. What's more, its development platform is strikingly similar to Moderna's. But does that mean it'll be able to wow investors in the same way?
This is a typical pre-product biotech
Aside from its coronavirus candidate, Inovio's biggest appeal is its DNA medicine platform. In theory, the platform can rapidly develop and jump-start the manufacturing of new medicines that are subsequently safe and effective.
In terms of its clinical-stage projects, it has two coronavirus vaccines in phase 3 trials, four other infectious disease programs, a trio of immuno-oncology projects, and a handful of others.
But although Moderna's coronavirus candidate advanced through clinical trials to get commercialized with hardly any incident, Inovio ran into a regulatory hurdle that took more than a year to completely navigate, causing it to lose the vaccine race.
And since then, its stock has yet to recover.
If there's any hope for Inovio to become the next Moderna, it'll need to commercialize its coronavirus vaccine and start raking in revenue. Then, it'll need to do something far more difficult: differentiate itself from its larger competitor.
Are DNA medicines the next mRNA medicines?
Differentiation is going to be hard for this vaccine stock because, in principle, Inovio's medicines use a similar scientific approach to Moderna's.
Whereas Moderna's vaccines are comprised of a lipid nanoparticle that carries messenger RNA (mRNA) into a patient's cells after injection, Inovio uses a special device called the Cellectra, which inserts circular strands of DNA into a patient's skin cells directly. From there, broadly speaking, both platforms aim to get the patient's cells to produce viral antigens that will in turn be recognized by the immune system and prompt a response from it that builds immunity.
Both systems enable manufacturers to easily customize the genetic sequence they include in their shot. That means Inovio's vaccine could be as easy to update to account for new viral variants as Moderna's is.
Like the larger company, Inovio has already initiated the development of a new jab that's specific to the omicron variant. And the active ingredients for both types of medicine are relatively inexpensive to manufacture.
However, Inovio's medicines may have a couple of advantages that Moderna's don't. Doses of its jab are expected to be shelf-stable at room temperature for more than a year, which dramatically simplifies the logistics of vaccine distribution and storage. It's also possible that the Cellectra device might be more efficient at delivering DNA than Moderna's lipid nanoparticles are at delivering mRNA.
Ultimately, that could lead to the company's DNA medicines being cheaper to produce and administer. But that's unlikely to matter if Moderna can develop medicines for the same indications more rapidly with its vast advantage in resources. Whereas Inovio had trailing research and development expenses of $183.2 million, Moderna's topped $2.1 billion.
Inovio's moment might not be over, but it's not a stock for everyone
With no real moat to protect the market share of its future products from players like Moderna, even a victory with its coronavirus candidate might not be enough to propel Inovio to the same heights as the mRNA company. Still, that doesn't mean it's doomed to be a poor investment.
If its coronavirus jab gets out the door, Inovio will start to realize far more revenue than ever before, and it'll have more cash to invest in making new medicines. Especially if management opts to focus the pipeline on areas where powerful competitors aren't going, the business could build a profitable niche for itself.
T cell responses to SARS-CoV-2 spike cross-recognize Omicron. Nature (2022).
Received
27 December 2021
Accepted
20 January 2022
Published
31 January 2022
The SARS-CoV-2 Omicron variant has multiple Spike (S) protein mutations1,2 that contribute to escape from antibody neutralization3–6 and reduce vaccine protection from infection7,8. The extent to which other components of the adaptive response such as T cells may still target Omicron and contribute to protection from severe outcomes is unknown. We assessed the ability of T cells to react with Omicron spike in participants who were vaccinated with Ad26.CoV2.S, BNT162b2, or unvaccinated convalescent COVID-19 patients (n=70). We found that 70-80% of the CD4+ and CD8+ T cell response to spike was maintained across study groups. Moreover, the magnitude of Omicron cross-reactive T cells was similar to Beta and Delta variants, despite Omicron harboring considerably more mutations. In Omicron-infected hospitalized patients (n=19), there were comparable T cell responses to ancestral spike, nucleocapsid and membrane proteins to those patients hospitalized in previous waves dominated by the ancestral, Beta or Delta variants (n=49). Thus, despite Omicron’s extensive mutations and reduced susceptibility to neutralizing antibodies, the majority of T cell responses, induced by vaccination or infection, cross-recognize the variant. It remains to be determined whether well-preserved T cell immunity to Omicron contributes to protection from severe COVID-19, and is linked to early clinical observations from South Africa and elsewhere9–12.
https://www.nature.com/articles/s41586-022-04460-3
1/21/22 BofA analyst Geoff Meacham upgraded Inovio to Neutral from Underperform with a price target of $10, up from $8. The analyst cites the stock's recent weakness and contends that the majority of remaining COVID-19 value has been removed from valuation following the recent 18% year-to-date pullback. Meacham adds that Inovio's commercial outlook for its COVID-19 vaccine has not changed, and the data generated from the program has demonstrated a favorable safety-profile and robust efficacy.
The Inovio Pharmaceuticals Thesis: While the stock has shed 18% year to date, data generated from the COVID-19 program seems to suggest “a favorable safety profile and robust efficacy,” which “bolsters our confidence in Inovio’s DNA vaccine platform,” Meacham said in the upgrade note.
“And while we think the emergence of C-19 variants has kept investors acutely focused on INO-4800, we expect interest to return to the non-C-19 pipeline in 2022, which we believe has more attractive opportunities,” the analyst wrote.
“In fact, we think VGX-3100 (HPV program) and INO-5401 (GBM program) will be the main value drivers for Inovio moving forward, and while we don’t expect any catalysts for these programs in 1H22, we expect readouts for INO-4500 in Lassa fever and INO-3107 in RRP in 1H22 to further de-risk the platform and add momentum to the story,” he added.
Advaccine is expediting Sinovac+4800 and 4800+Booster to grease the skid for HK IPO. They are extremely motivated, will ace it with China ???? gov support. 8% royalty for 1.45B ppl * 1-2 boosters per year plus ex-China. Coronavac is most popular.
First picx is San Diego Research Center, parking lot is modestly full for Sat 1/29/22 as Ino is working furiously on 4800/4802 against Omicron report, INNOVATE interim readout analysis.
• Molecular biology, cell biology, and clinical immune monitoring
• Research-grade DNA manufacture capabilities
• 6,000sfdedicatedBSL-2researchlab (wet lab and cell culture)
• 5,000sfcGLPlabstoprocess,store,and analyze human clinical trial samples
• WellestablishedQAcapability
Second picture is SD Device Engineering and Manufacturing Facility
• Electroporation delivery device and consumable design, engineering, and manufacturing
•Deliverydevicetestinganddistribution
• 53,000sffacilityopenedinJuly2017
• ISO13485andMDDcertifiedbyTÜV America in San Diego
No foreign CV vaccine was EUA’ed in China. China's drug regulator has approved the country's first mixed-vaccine trial, a company involved in the study said, as the rapid spread of the Delta variant raises concern about the efficacy of domestically produced jabs.
The trial will test the efficacy of combining an "inactivated" vaccine made by China's Sinovac with a DNA-based one developed by Inovio.
4800 is brilliantly positioned as pGX9501 jointly developed by Advaccine and Ino. Therefore, it’s considered as the first domestic DNA vaccine. As such it received full China gov support and expedited. Remember Tesla plant in Shanghai from ground breaking to production is only 11 months due to full China gov support.
Chairman Bin Wang is well connected, and greatly respected by China ???? gov. HK IPO is predicated on
pGX9501 interim readout early Mar, then EUA.
Coronavac is the most popular vaccine in the world, applied to most ppl, opening up huge markets worldwide.
https://stocktwits.com/Iluvufor30s/message/431682358
according to Oppenheimer’s Hartaj Singh.
“The lifting of the US FDA partial clinical hold is important, for regulatory and future commercial purposes,” the 5-star analyst said. “With the pandemic potentially receding in the US (COVID-19 infections falling), the company still expects to recruit less than 10% of its INNOVATE patients from the US. However, the gravitas of an FDA imprimatur and the potential of future US approval are important.”
There have been other recent positive developments. India has also signed up for the trial, and INO and the Colombia Ministry of Health and Social Protection have signed a memorandum of understanding (MoU) to develop Covid-19 and possibly other vaccines. Additionally, realizing INO-4800’s inherent advantages - the vaccine can be kept at room temperature for more than a year – the WHO has jumped on board and initiated a global Phase 3 trial. Singh anticipates interim readouts from the global Phase 3 INNOVATE study “as early as 1H22.”
Oppenheimer analyst Hartaj Singh makes the argument that progress on Inovio's INO-4800 coronavirus vaccine, combined with its INO-5401 cancer vaccine and its Human papillomavirus (HPV) vaccine VGX-3100, could drive Inovio stock higher. How much higher?
Of the three biggest vaccine candidates, Singh sees INO-4800 as the one offering the most immediate value, and contributing $20 per share to his $35 overall target price.
Less well known than competing coronavirus vaccines from Pfizer or Moderna, Singh notes that INO-4800 has several advantages to recommend it. For one, it's DNA-based, and thus can theoretically be modified to combat mutated versions of the COVID-19 coronavirus. For another, it offers a better "safety/tolerability profile," that could recommend it as an alternative to other vaccines.
And for a third, INO-4800 is said to be both easier to store and has a longer shelf life than other vaccines on the market today, which might make it more suitable for stockpiling against future coronavirus outbreaks.
VGX-3100 is the next most valuable of Inovio's vaccine candidates, thinks Singh, being worth perhaps $7 a share. It's also, says the analyst, the vaccine with the "highest sustainability and potential upside on commercialization" for Inovio, as HPV will presumably remain a problem long after the coronavirus pandemic has gone away. Singh also sees "potential to expand into other (pre)cancerous indications" based on research done for VGX-3100.
Finally, Singh sees INO-5401 as worth perhaps $5 a share to Inovio stock. In the analyst's view, INO-5401 could be a "potential breakthrough" drug for treating patients with glioblastoma, a cancer that has not seen a real improvement in treatment options "for decades."
Other vaccine candidates in the pipeline, plus Inovio's cash on hand, make up the final $3 of the analyst's target valuation for Inovio.
Not all this value may be immediately apparent to investors, however. Notably, Singh admits that revenues at Inovio over the past three years have been measured in the low single digits of millions of dollars. It won't be until 2022, says the analyst before sales really grow appreciably. But once these vaccines begin coming to market, the analyst sees significant growth potential: $656 million in sales in 2022, twice that in 2023, $2.1 billion in 2024, and $3 billion in 2025.
Indeed, by 2025, the analyst forecasts that Inovio could be earning $6.48 per share, per year, making today's price target of $35 look cheap indeed.
In the meantime, though, investors will need to be patient. Profits will only emerge alongside sales in 2022 -- $1.46 per share.
1/27/22 “I cannot speak for them but I understand it is proceeding well. I am sure Advaccine will announce something when ready.”
Q: Did Advaccine Finish recruiting for 2 trials:
Sinovac’s Coronavac + 4800 heterologous and homologous?
11/8/21 China approves first mixed-vaccine trial as Delta spreads
Study execute time:
From 2021-11-30 To 2022-07-31
http://www.chictr.org.cn/hvshowproject.aspx?id=96875
https://www.france24.com/en/live-news/20210811-china-approves-first-mixed-vaccine-trial-as-delta-spreads
Preclinical work has found that "two different vaccine applications... produce an even stronger and more balanced immune response", Advaccine chairman Wang Bin said in the statement.
Beijing is yet to approve any foreign vaccines for domestic use.
Dr. Fauci reveals his worst-case scenario for 2022 and it involves a new variant
What is the worst case scenario for the COVID-19 pandemic? Here’s what Dr. Fauci said
By Herb Scribner on January 26, 2022 11:00 pm
The year 2022 has barely begun and Dr. Anthony Fauci already has a worst-case scenario prediction.
The news: Fauci, the White House medical adviser on the coronavirus, recently told Yahoo Finance! that the worst-case scenario for 2022 would be a COVID-19 variant that can evade vaccines and natural immunity.
“The worst-case scenario is we’re on our way there and we get hit with another variant that actually eludes the immune protection. I hope that’s not the case,” Fauci said.
Fauci said the omicron variant can already evade vaccines to some extent, but the vaccine prevents hospitalizations and death. Immunity and vaccination may stop the worst-case scenario, he said.
“The thing that makes it less likely, but not impossible, is that by that time, you will have so many people vaccinated and already infected, that you might have a level of community protection that may not get you away from the next variant, but would protect you from the severity of the next variant.”
Another prediction: Dr. Mark Dybul, a professor at Georgetown University Medical Center’s Department of Medicine and immunologist, told Fortune that he expects to see a vaccine-resistant variant by spring 2022 — at least based on trends for the virus from the last two years.
“The faster we get boosted, the better off we’ll be for the next couple of months,” he said. “Sadly, every prediction I’ve made has pretty much come true. I hope I’m wrong this time, but I think by March, April, May, we will have a fully vaccine-resistant variant.
“There’s simply no way you can have such low rates of vaccination around the world with the virus ping-ponging between vaccinated and unvaccinated people.
“I’m an immunologist. The probability of us seeing a vaccine-resistant strain is very high.”
Why this matters: Of course, we may have already seen this with the omicron COVID-19 variant, which has evaded vaccines and caused many breakthrough cases.
However, it’s still a reminder that there are more troubling potential variants out there. Vaccinations can help people stay safe from these dangerous variants, though.
https://www.deseret.com/coronavirus/2022/1/26/22894930/dr-fauci-worst-case-scenario-2022-new-covid-variant
11/8/21 China approves first mixed-vaccine trial as Delta spreads
Study execute time:
From 2021-11-30 To 2022-07-31
Finished recruiting for 2 trials.
http://www.chictr.org.cn/hvshowproject.aspx?id=96875
https://www.france24.com/en/live-news/20210811-china-approves-first-mixed-vaccine-trial-as-delta-spreads
China's drug regulator has approved the country's first mixed-vaccine trial, a company involved in the study said, as the rapid spread of the Delta variant raises concern about the efficacy of domestically produced jabs.
The trial will test the efficacy of combining an "inactivated" vaccine made by China's Sinovac with a DNA-based one developed by US pharmaceutical company Inovio, a statement issued on Tuesday said.
The statement was put out by Advaccine Biopharmaceuticals Suzhou, Inovio's trial partner in China.
Preclinical work has found that "two different vaccine applications... produce an even stronger and more balanced immune response", Advaccine chairman Wang Bin said in the statement.
There are several types of Covid vaccines, including those using an inactivated or weakened virus to generate an immune response, and more cutting-edge RNA- or DNA-based jabs that use engineered versions of the coronavirus' genetic code to create a protein that safely prompts an immune response.
Five out of the seven vaccines approved in China are two-shot inactivated vaccines.
Their published efficacy lags RNA jabs by Pfizer-BioNTech and Moderna, which have pre-Delta success rates above 90 percent.
The World Health Organization has said there is still not enough data to say whether using two different vaccines together is safe or can boost immunity.
Inovio has not published any efficacy data from its global clinical trials. It is the first DNA-based vaccine to be trialled in China.
China is battling its worst coronavirus outbreak in months, with officials saying many of those infected had already been vaccinated.
This has added to calls for China's two biggest vaccine producers -- state-run Sinopharm and privately owned Sinovac -- to provide data proving their jabs work against the Delta variant.
Beijing is yet to approve any foreign vaccines for domestic use.
https://ir.inovio.com/news-releases/news-releases-details/2021/INOVIO-Reports-Third-Quarter-2021-Financial-Results/default.aspx
INOVIO continues to study the boosting capabilities of INO-4800 following an initial primary vaccination series using a different COVID-19 vaccine series (heterologous) or with INO-4800 (homologous). During the third quarter, INOVIO's partner Advaccine received regulatory authorization to conduct two clinical trials in China investigating boosting with INO-4800. The studies will include prime-boost sequential immunizations using INO-4800 and an inactivated COVID-19 vaccine.
Inovio Undervalued On Potential 2022 Catalyst
Jan. 26, 2022 5:36 AM by William Meyers
Summary
Inovio’s stock price is back near pre-Covid levels.
It is nearing commercialization of its HPV dysplasia vaccines.
It might even still succeed in the Covid vaccine game.
Inovio (INO) is a leader in DNA plasmid-based vaccines. It already had an extensive pipeline of potential vaccines against a variety of indications back in 2019. When the Covid pandemic hit, it quickly announced it was developing a DNA vaccine for Covid. But delays from regulators kept pushing back that timeline. Today Inovio’s Covid vaccine is in Phase 3 trials, but no date has been announced for final data. Given all this, it is not surprising the stock price surged from a base of around $2.25 per share in 2019 to a peak of $33.79 on June 22, 2020. Lately it has slumped to close at $4.04 on January 24, 2022, giving the company a market capitalization of just $850 million.
While I believe there is still the possibility of eventually seeing revenue from its Covid vaccine, or from an update engineered to handle variants, in this article I will focus on the HPV dysplasia pipeline. I believe that this segment of the pipeline, by itself, can propel Inovio to commercial success and a significantly higher stock price within the next few years.
VGX-3100 for cervical dysplasia
In March 2021, Inovio reported its first VGX-3100 Phase 3 trial for cervical dysplasia had positive results. The disease is caused by HPV infections and is also known as HSIL or high-grade squamous intraepithelial lesions. More simply, pre-cancers. This was the first time a DNA plasmid medicine achieved efficacy endpoints in a Phase 3 clinical trial. Topline results were that 23.7% of patients achieved histological regression with viral clearance versus 11.3% in the placebo group. Positive secondary results included HPV clearance. More detailed VGX-3100 results were released in December at the 34th International Papillomavirus Conference. Notably patients treated with VGX-3100 who were cleared of HPV at week 36 remained clear of HPV-16 and HPV-18 at week 88. Then in late December Inovio announced completion of enrollment in the second Phase 3 VGX-3100 study. Top line safety and efficacy data for this REVEAL2 trial should be available in the second half of 2022. In addition, with partner Qiagen, a biomarker to predict which patients are likely to have positive results is under development. A third Phase 3 trial is being run by partner ApolloBio in China to help gain regulatory approval there.
There is no guarantee yet, but it looks to me like VGX-3100 is headed towards regulatory approval and commercialization for cervical dysplasia. Guessing how much income could be generated is highly dependent on the pricing of the therapy. Technically it is a vaccine, but I expect it to be priced more like a cancer therapy. In America alone there are at least 250,000 cervical dysplasia diagnoses annually. That may go down over time as preventative vaccines like Gardasil are given to more adolescent women, but given the opposition to the vaccine, it is not likely to go away during the patent life of VGX-3100. The current treatments, once the disease advances to high-grade dysplasia, are various forms of surgery. Failure to treat can lead to cancer. I would be surprised if the vaccine treatment is not in the $1,000 to $10,000 range in the U.S.
VGX-3100 for vulvar neoplasia
VGX-3100 is also being used to treat vulvar neoplasia. Current treatments are like those for cervical dysplasia. It is, however, far less common, with only about 6,000 new U.S. cases annually. In January 2021, Inovio reported positive interim results from the open-label Phase 2 trial of VGX-3100 to treat HPV-16 and HPV-18-associated vulvar HSIL in 24 patients; 5 patients withdrew before evaluation. At six months post-treatment a 25% or more reduction in HPV-16/18-associated vulvar HSIL was observed for 63% of participants treated with VGX-3100. Three patients with histology data (15%) resolved their vulvar HSIL and had no HPV-16/18 virus detectable in the healed area. The trial will continue for 18 months following the last dose.
VGX-3100 for anal dysplasia
In December 2021 at the 34th International Papillomavirus Conference, new positive Phase 2 data was released for VGX-3100 for anal dysplasia, which can lead to anal cancer. Inovio is in discussions with the FDA on Phase 3 trial options for anal and vulvar dysplasia.
Other pipeline highlights
Inovio is working with Regeneron (REGN) to find a cure for glioblastoma, the most aggressive form of brain cancer. Phase 2 data has been good so far for the combination of INO-5401, INO-9012, and Libtayo, a PD-1 inhibitor. In late 2020, Inovio shared encouraging interim OS18 (overall survival at 18 months) data, which also demonstrated immunogenicity and tolerability in a majority of patients. We are now waiting for 24-month overall survival data from the Phase 2 trial. While there is an urgent need for an effective glioblastoma therapy, meaning the possibility of FDA conditional approval based on Phase 2 trial data, more likely a Phase 3 trial will be required. It looks like commercialization is not likely before 2026. If approved by the FDA and other regulators the combination could be a very large revenue generator.
In Q4 2022 Inovio announced full enrollment in its Phase 1B clinical trial for INO-4500 vaccine for Lassa fever. This is the first vaccine clinical trial for Lassa fever conducted on the African continent, where the disease is endemic. The trial enrolled 220 adult participants with the primary endpoints of evaluating safety and immunogenicity.
The complete Inovio pipeline includes several other DNA vaccines for infectious diseases and cancers, most at earlier stages of development.
Cash and burn rate
At the end of Q3 2021 Inovio had $395 million in cash and short-term investments. Revenue, mainly from collaborative R&D arrangements, was $291 thousand. Operating expenses were $60.2 million. If we take $60 million per quarter as a cash burn rate, Inovio can operate into at least Q1 2023 on its current cash. It could also raise more money through licensing. If VGX-3100 cervical dysplasia results are positive and submitted for FDA approval, I would expect additional stock to be issued to raise money for commercialization efforts.
Conclusion
With its VGX-3100 dysplasia HPV vaccine nearing commercialization, I think Inovio is highly likely to be headed towards commercial success. If it also gets approval for its Covid vaccine, it looks like the pandemic will still be with us, somewhere in the world, so sales of that are possible as well [something I discounted when other vaccines became available in early 2021]. I hope that Inovio will also be able to use commercial revenue to progress and expand its potential DNA vaccine therapy pipeline. The current market capitalization of $850 million includes some assumption of success, but since I expect VGX-3100 revenue to top $250 million annually at some point, in my view Inovio is currently undervalued. Positive Phase 2 glioblastoma results could also be a catalyst for a higher stock price. There is risk that the second Phase 3 VGX-3100 trial results will not be positive, or that the FDA will find some reason to reject the vaccine, or that the market for the vaccine will be smaller than I anticipate. Those who are risk-averse would probably want to wait to see further results before investing.
https://seekingalpha.com/article/4481675-inovio-stock-undervalued-on-potential-2022-catalyst
MERS, dMAb, HPV, Cancer vaccine, EP patents granted
DNA antibody constructs for use against middle east respiratory syndrome coronavirus
Patent number: 11230592
Abstract: Disclosed herein is a composition including a recombinant nucleic acid sequence that encodes an antibody to a Middle East Respiratory Syncytial Coronavirus (MERS-CoV) viral antigen. Also disclosed herein is a method of generating a synthetic antibody in a subject by administering the composition to the subject. The disclosure also provides a method of preventing and/or treating an MERS-CoV virus infection in a subject using said composition and method of generation.
Type: Grant
Filed: September 27, 2018
Date of Patent: January 25, 2022
Assignees: THE WISTAR INSTITUTE OF ANATOMY AND BIOLOGY, INOVIO PHARMACEUTICALS, INC.
Inventors: David Weiner, Trevor R F Smith, Kar Muthumani
DNA antibody constructs and method of using same
Patent number: 11208470
Abstract: Disclosed herein is a composition including a recombinant nucleic acid sequence that encodes an antibody. Also disclosed herein is a method of generating a synthetic antibody in a subject by administering the composition to the subject. The disclosure also provides a method of preventing and/or treating disease in a subject using said composition and method of generation.
Type: Grant
Filed: September 26, 2018
Date of Patent: December 28, 2021
Assignees: The Trustees of the University of Pennsylvania, Inovio Pharmaceuticals, Inc.
Inventors: David Weiner, Karuppiah Muthumani, Seleeke Flingai, Niranjan Sardesai
TUMOR-SPECIFIC NEOANTIGENS AND METHODS OF USING THE SAME
Publication number: 20210361755
Abstract: The disclosure relates to methods of manufacturing individualized vaccines that comprise nucleic acid molecules that encode one or more neoantigens specific for antigens that are expressed by a tumor in a subject. Compositions comprising coding regions encoding neoantigens organized in a pattern of nucleic acid sequences are also disclosed as well as methods of immunizing a subject using the same.
Type: Application
Filed: May 28, 2019
Publication date: November 25, 2021
Applicants: THE WISTAR INSTITUTE, INOVIO PHARMACEUTICALS, INC., GENEOS THERAPEUTICS, INC.
Inventors: Elizabeth Kennedy Duperret, Alfredo Perales Puchalt, David Weiner, Niranjan Y. Sardesai
Cancer vaccines targeting BORIS and uses thereof
Patent number: 11154601
Abstract: Disclosed herein are nucleic acid molecules comprising one or more nucleic acid sequences that encode a synthetic consensus BORIS antigen. Vectors, compositions, and vaccines comprising one or more nucleic acid sequences that encode a synthetic consensus BORIS antigen are disclosed. Methods of treating a subject with a BORIS-expressing tumor and methods of preventing a BORIS-expressing tumor are disclosed. A synthetic consensus BORIS antigen is disclosed.
Type: Grant
Filed: December 13, 2018
Date of Patent: October 26, 2021
Assignee: Inovio Pharmaceuticals, Inc.
Inventors: Jian Yan, Anna Slager, Bradley Garman, Neil Cooch
Cancer vaccines targeting mesothelin and uses thereof
Patent number: 11154602
Abstract: Disclosed herein are nucleic acid molecules comprising one or more nucleic acid sequences that encode a modified consensus mesothelin antigen. Vectors, compositions, and vaccines comprising one or more nucleic acid sequences that encode a modified consensus mesothelin antigen are disclosed. Methods of treating a subject with a mesothelin-expressing tumor and methods of preventing a mesothelin-expressing tumor are disclosed. Modified consensus mesothelin antigen is disclosed.
Type: Grant
Filed: December 13, 2018
Date of Patent: October 26, 2021
Assignee: Inovio Pharmaceuticals, Inc.
Inventors: Jian Yan, Anna Slager, Bradley Garman, Neil Cooch
MERS-CoV vaccine
Patent number: 11135284
Abstract: Disclosed herein is a vaccine comprising a Middle East Respiratory Syndrome coronavirus (MERS-CoV) antigen. The antigen can be a consensus antigen. The consensus antigen can be a consensus spike antigen. Also disclosed herein is a method of treating a subject in need thereof, by administering the vaccine to the subject.
Type: Grant
Filed: February 4, 2020
Date of Patent: October 5, 2021
Assignees: The Trustees of the University of Pennsylvania, Inovio Pharmaceuticals, Inc.
Inventors: David Weiner, Karuppiah Muthumani, Niranjan Y. Sardesai
Foot and mouth disease virus (FMDV) consensus proteins, coding sequences therefor and vaccines made therefrom
Patent number: 11124545
Abstract: Provided herein is a nucleic acid comprising consensus amino acid sequence of foot-and-mouth disease FMDV VP1-4 coat proteins of FMDV subtypes A, Asia 1, C, O, SAT1, SAT2, and SAT3 as well as plasmids and vaccines expressing the sequences. Also provided herein is methods for generating an immune response against one or more FMDV subtypes using the vaccine as described above as well as methods for deciphering between vaccinated mammals with the vaccine and those that are infected with FMDV.
Type: Grant
Filed: May 20, 2019
Date of Patent: September 21, 2021
Assignees: The Trustees of the University of Pennsylvania, Inovio Pharmaceuticals, Inc.
Inventors: David B. Weiner, Bernadette Ferraro, Jian Yan, Patricia A. Brown, Rodney A. Bowling, Douglas R. Kern, Mathura P. Ramanathan, Niranjan Y. Sardesai, Karuppiah Muthumani
Checkpoint inhibitor and vaccine combinations and use of same for immunotherapy
Patent number: 11116838
Abstract: Disclosed herein is a vaccine comprising an antigen and checkpoint inhibitor. Also disclosed herein is a method for enhancing an immune response in a subject. The method may comprise administering the vaccine to the subject in need thereof.
Type: Grant
Filed: January 28, 2016
Date of Patent: September 14, 2021
Assignees: The Trustees of the University of Pennsylvania, INOVIO PHARMACEUTICALS, INC.
Inventors: David Weiner, Karuppiah Muthumani, Niranjan Sardesai
Multiple tissue layer electroporation applicator and device
Patent number: 11097099
Abstract: The present invention relates to dual depth electroporation devices capable of electorporating both muscle tissue and skin tissue in a single application in order to generate a broad immune response in a subject, and uses of the same.
Type: Grant
Filed: March 1, 2011
Date of Patent: August 24, 2021
Assignee: Inovio Pharmaceuticals, Inc.
Inventors: Kate Broderick, Feng Lin, Jay McCoy, Stephen V Kemmerrer, Rune Kjeken
Filovirus consensus antigens, nucleic acid constructs and vaccines made therefrom, and methods of using same
Patent number: 11091518
Abstract: Nucleic acid molecules and compositions comprising one or more nucleic acid sequences that encode a consensus Ebolavirus glycoproteinimmunogens are disclosed. The coding sequences optionally include operable linked coding sequence that encode a signal peptide. Immunomodulatory methods and methods of inducing an immune response against Ebolavirus are disclosed. Method of preventing Ebolavirus and methods of treating individuals infected with Ebolavirus are disclosed. Consensus Ebolavirus proteins are disclosed.
Type: Grant
Filed: May 5, 2017
Date of Patent: August 17, 2021
Assignees: The Trustees of the University of Pennsylvania, THE WISTAR INSTITUTE OF ANATOMY AND BIOLOGY, Inovio Pharmaceuticals, Inc.
Inventors: David B. Weiner, Ami Patel, Jian Yan
Electroporation device with detachable needle array with lock-out system
Patent number: 11071859
Abstract: An electroporation device with a needle array removably attached thereto, the needle array having a body, a shroud movable with respect to the body between a rest position and one or more actuated positions, and an auto-lock assembly. Where the auto-lock assembly is adjustable between a locked configuration, where the shroud is not movable with respect to the body, and an unlocked configuration, where the shroud is movable with respect to the body, and where biasing the shroud from the rest position to the one or more actuated positions and back to the rest position adjusts the auto-lock from the unlocked configuration to the locked configuration.
Type: Grant
Filed: December 30, 2016
Date of Patent: July 27, 2021
Assignee: Inovio Pharmaceuticals, Inc.
Inventors: Beat Stadelmann, Stephen Kemmerrer, Alejandro Campillo-Agusti, Eduardo Ho, Nathan Lovell, Steven Masterson
Consensus prostate antigens, nucleic acid molecule encoding the same and vaccine and uses comprising the same
Patent number: 11045535
Abstract: Provided herein are consensus amino acid sequences of prostate antigens that are capable of breaking tolerance in a targeted species, including PSA, PSMA, STEAP and PSCA antigens. Also provided are nucleic acid sequences that encode one or more consensus amino acid sequences of prostate antigens PSA, PSMA, STEAP and PSCA, as well as genetic constructs/vectors and vaccines expressing the sequences. Also provided herein are methods for generating an autoimmune response against prostate cancer cells by administering one or more of the vaccines, proteins, and/or nucleic acid sequences that are provided.
Type: Grant
Filed: January 31, 2018
Date of Patent: June 29, 2021
Assignees: The Trustees of the University of Pennsylvania, Inovio Pharmaceuticals, Inc.
Inventors: David Weiner, Jian Yan, Bernadette Ferraro, Niranjan Y. Sardesai, Mathura P. Ramanathan
Intradermal jet injection electroporation device
Patent number: 11027071
Abstract: An jet injection and electroporation device for use with an agent cartridge defining a volume containing a pre-measured dose of agent therein, the electroporation device including a housing having an axis extend therethrough, a nozzle at least partially positioned within the housing, and a cavity sized to receive at least a portion of the agent cartridge therein. The device also includes an array having a plurality of electrodes extending therefrom, a propulsion cartridge configured to operatively engage the cartridge when the agent cartridge is positioned within the cavity; and a power supply in electrical communication with the array.
Type: Grant
Filed: December 28, 2016
Date of Patent: June 8, 2021
Assignee: Inovio Pharmaceuticals, Inc.
Inventors: Jay McCoy, Kate Broderick, Stephen Kemmerrer
Vaccines having an antigen and interleukin-21 as an adjuvant
Patent number: 11007265
Abstract: Disclosed herein is a vaccine comprising an antigen and IL-21. Also disclosed herein are methods for increasing an immune response in a subject. The methods may comprise administering the vaccine to the subject in need thereof.
Type: Grant
Filed: November 6, 2018
Date of Patent: May 18, 2021
Assignees: THE TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA, INOVIO PHARMACEUTICALS, INC.
Inventors: David B. Weiner, Matthew P. Morrow
Cancer vaccines and methods of treatment using the same
Patent number: 11007255
Abstract: The invention provides a vaccine comprising a nucleic acid molecule that encodes a dog telomerase reverse transcriptase (dTERT) antigen, as well as methods of using the vaccine to induce an immune response against a TERT and to treat cancer in a mammal.
Type: Grant
Filed: February 3, 2017
Date of Patent: May 18, 2021
Assignee: Inovio Pharmaceuticals, Inc.
Inventor: Jian Yan
Vaccines with interleukin-33 as an adjuvant
Patent number: 10933130
Abstract: Disclosed herein is a vaccine comprising an antigen and IL-33. Also disclosed herein is a method for increasing an immune response in a subject in need thereof. Further disclosed herein is a method for treating cancer in a subject in need thereof. The methods may comprise administering the vaccine to the subject.
Type: Grant
Filed: August 30, 2018
Date of Patent: March 2, 2021
Assignees: The Trustees of the University of Pennsylvania, Inovio Pharmaceuticals, Inc.
Inventors: David Weiner, Daniel Villarreal, Matthew Morrow, Jian Yan
Vaccines with CD40 ligand as an adjuvant
Patent number: 10925961
Abstract: Disclosed herein is a vaccine comprising an antigen and CD40L. Also disclosed herein are methods for increasing an immune response in a subject. The methods may comprise administering the vaccine to the subject in need thereof.
Type: Grant
Filed: March 18, 2016
Date of Patent: February 23, 2021
Assignees: The Trustees of the University of Pennsylvania, INOVIO PHARMACEUTICALS. INC.
Inventors: David Weiner, Matthew Morrow, Megan Wise
Vaccines for human papilloma virus and methods for using the same
Patent number: 10905755
Abstract: Improved anti-HPV immunogens and nucleic acid molecules that encode them are disclosed. Immunogens disclosed include those having consensus HPV39 E6E7 and HPV45 E6E7. Pharmaceutical composition, recombinant vaccines comprising DNA plasmid and live attenuated vaccines are disclosed as well methods of inducing an immune response in an individual against HPV are disclosed.
Type: Grant
Filed: March 11, 2019
Date of Patent: February 2, 2021
Assignees: The Trustees of the University of Pennsylvania, Inovio Pharmaceuticals, Inc.
Inventors: David Weiner, Jian Yan
Oral mucosal electroporation device and use thereof
Patent number: 10905870
Abstract: The present invention relates to electroporation (EP) devices that are able to generate an electroporation causing electrical field at the mucosal layer, and preferably in a tolerable manner. Further, it includes the generation of a protective immune response, cellular and/or humoral, using the oral EP device along with a genetic construct that encodes an immunogenic sequence.
Type: Grant
Filed: November 12, 2018
Date of Patent: February 2, 2021
Assignee: Inovio Pharmaceuticals, Inc.
Inventors: Stephen V. Kemmerrer, Kate Broderick, Jay McCoy
https://patents.justia.com/assignee/inovio-pharmaceuticals-inc
1/25/22 SARS-CoV-2 DNA Vaccine INO-4800 Induces Durable Immune Responses Capable of Being Boosted in a Phase 1 Open-Label Trial
Received: 27 September 2021
Published: 25 January 2022
Abstract
Background
Additional SARS-CoV-2 vaccines that are safe and effective as primary vaccines and boosters remain urgently needed to combat the COVID-19 pandemic. We describe the safety and durability of the immune responses following two primary doses and a homologous booster dose of an investigational DNA vaccine (INO-4800) targeting the full-length spike antigen.
Methods
Three dosage strengths of INO-4800 (0.5 mg, 1.0 mg, and 2.0 mg) were evaluated in 120 age-stratified healthy adults. Intradermal injection of INO-4800 followed by electroporation at 0 and 4 weeks preceded an optional booster 6-10.5 months after the second dose.
Results
INO-4800 appeared well tolerated, with no treatment-related serious adverse events. Most adverse events were mild and did not increase in frequency with age and subsequent dosing. A durable antibody response was observed 6 months following the second dose; a homologous booster dose significantly increased immune responses. Cytokine producing T cells and activated CD8+ T cells with lytic potential were significantly increased in the 2.0 mg dose group.
Conclusion
INO-4800 was well tolerated in a 2-dose primary series and as a homologous booster in all adults, including the elderly. These results support further development of INO-4800 for use as a primary vaccine and as a booster.
https://academic.oup.com/jid/advance-article/doi/10.1093/infdis/jiac016/6515374?login=false
238 Discussion
239 This report provides results for the expansion of a Phase 1 trial to include older and elderly
240 participants and an optional booster dose with the aim to evaluate the safety, tolerability, and
241 immunogenicity of INO-4800, a SARS-CoV-2 vaccine encoding the S protein[14], including the
242 immune responses 6 months following dose 2 and 2 weeks following the optional booster dose.
243 INO-4800 appeared to be well-tolerated at all three dose levels, with no treatment-related
244 serious adverse events (SAEs) reported. Most AEs were mild in severity and did not increase in
245 frequency with age and subsequent dosing. These results are consistent with the severity of
246 AEs and lack of treatment-related SAEs observed in the U.S. Phase 2 trial comparing the 1.0
247 mg and 2.0 mg doses of INO-4800 in approximately 400 subjects[15] and those studies
248 conducted outside the U.S. by Inovio collaborators (International Vaccine Institute, Advaccine –
249 manuscripts in preparation). The lower frequency of treatment-related AEs reported by older
250 and elderly participants in our study is consistent with findings of other studies evaluating
251 SARS-CoV-2 vaccines[19, 20]. Weaker inflammatory reactions consequent to
252 immunosenescence may explain the lower incidence of AEs among elderly participants[21, 22].
253 Induction of both humoral and cellular responses were observed across all three dose groups,
254 inclusive of binding and neutralizing antibodies and cytokine producing T cells as well as
255 exhibiting lytic potential. Immunization with the 2.0 mg dose resulted in the highest GMTs of
256 neutralizing and binding antibodies as well as the highest magnitudes of IFN? production to
257 SARS-CoV-2 of any dose in all age groups tested, and the increases in antibody levels were
258 statistically significant above baseline at 6 months following dose 2. Importantly, increases in
259 both humoral and cellular immune responses were statistically significant following the booster
260 dose.
261 The contribution of the CD8+T cell response to vaccine efficacy has become increasingly
262 recognized as they have been detected early after vaccination[23] and due to their role in
263 controlling infection[24, 25]. Specifically, it has been established that CD8+T cells expressing
264 cytokines such as IFN? and TNF? as well as markers involved in activation status and
265 proliferation such as CD38 and Ki67 contribute to limiting disease severity during SARS-CoV-2
266 infection[24]. Additional studies have identified the expression of CD69 and CD137 on SARS-
267 CoV-2 specific CD8+T cells being associated with less severe disease[25]. This expanded
268 Phase 1 trial demonstrates that immunization with INO-4800 induces SARS-CoV-2 specific
269 CD8+T cells exhibiting these specific characteristics, suggesting the induction of a vaccine-
270 induced cellular response that has potential to protect against severe COVID-19. As VoCs
271 continue to emerge, the generation of cross-reactive activated CD8+T cells with lytic potential is
272 likely to play an important role in preventing severe disease. We have previously demonstrated
273 that vaccination with INO-4800 induces T cells and neutralizing antibodies that are active
274 against the parental SARS-CoV-2 strain as well as the B.1.1.7, B.1.351, and P.1 VoCs[26]. We
275 acknowledge limitations to this trial that include the relatively small study population and the
276 limited number of PBMCs available for testing across more than one assay. This trial was not
277 powered to formally compare immune responses between dose groups or age stratifications. In
278 addition, due to different immune assays and methodologies employed by various groups, it is
279 not possible to directly compare immune responses observed in this trial to those elicited from
280 other vaccine platforms or to determine if the magnitudes observed in this trial are sufficient to
281 confer clinical benefit.
282 The immune responses observed in the current trial and in our larger Phase 2 trial[15] support
283 advancing the 2.0 mg dose of INO-4800 to a Phase 3 efficacy evaluation. This dose has elicited
284 the highest binding and neutralizing antibody titers, the highest T-cell cytokine production from
285 both CD4+ and CD8+T cells, and the highest expression of markers associated with attenuation
286 of severe COVID-19 on CD8+T cells.
287 This trial demonstrated that immune responses elicited by a 2-dose primary series of INO-4800
288 could be boosted by a third dose without safety or tolerability concerns and positions INO-4800
289 as an important candidate for continued development as a stand-alone SARS-CoV-2 vaccine,
290 as well as for continued examination in combination approaches. The potential ability to
291 administer INO-4800 multiple times, with high tolerability, along with its ease of scalability and
292 thermostability, contribute to its potential value in combatting the COVID-19 pandemic.
Today and tomorrow 1/25-26/22 INO Virtual Meetings with Oppenheimer is private and separate from
Oppenheimer
32nd Annual Healthcare Conference
March 15-16, 2022 Virtual
This conference will provide investors a broad spectrum of public and private healthcare companies spanning all major sectors of the healthcare industry: bio & specialty pharmaceuticals; biotechnology; medical devices; life science tools and diagnostics; healthcare information technology and distribution; and healthcare providers and servicers.
https://www.oppenheimer.com/events/2022/32nd-annual-healthcare-conference.aspx