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UPenn Researchers Enrolling BRCA1/2 Carriers into Inovio hTERT Cancer Vaccine study
Apr 11, 2022 | Caroline Hopkins
NEW ORLEANS — Researchers at the University of Pennsylvania in collaboration with the drugmaker Inovio have launched a Phase I clinical trial assessing whether a cancer vaccine, dubbed INO 5401, can prevent high-risk breast cancer patients with BRCA1/2 germline mutations from relapsing and healthy individuals with these mutations from developing cancer at all.
Susan Domchek, executive director of the Basser Center for BRCA at the University of Pennsylvania, presented the trial details during the American Association for Cancer Research's annual meeting on Saturday. The study is enrolling participants to two groups: Cohort A includes 16 patients with BRCA1 or BRCA2 mutations who have had a prior diagnosis of invasive breast or ovarian cancer, pancreatic cancer, or prostate cancer and have completed adjuvant therapy with no clinical evidence of disease. Cohort B will include 28 healthy participants carrying BRCA1 or BRCA2 mutations.
The immuno-interception strategy that Domchek and her team are evaluating in the trial involves Plymouth Meeting, Pennsylvania-based Inovio's INO 5401, a DNA plasmid encoding hTERT, WT-1, and PSMA, alone or together with INO-9102, which encodes the gene for IL-12.
Following the vaccine, participants are given a small electric charge via an electroporation device called the Cellectra 2000 to increase the amount of vaccine taken up by muscle. Both cohort A and cohort B are separated into two treatment arms: one arm will receive INO 5401 followed by electroporation and one arm will received INO 5401 and INO 9102 together followed by electroporation.
Positive data from both the metastatic breast cancer setting and from a Phase I clinical trial of the strategy for solid tumor patients at a high risk of relapse offered the rationale for the Basser Center study to assess the feasibility for non-surgical prevention.
That earlier study, dubbed TRT-001, was published recently in the Journal for Immunotherapy of Cancer. Among 93 patients with breast, ovarian, and pancreatic cancers, among others, an earlier iteration of the Inovio vaccine, INO-1400, was not only immunogenic, but also safe. Immune responses were observed across all tumor types, and the vaccine increased a CD8-positive phenotype associated with improved overall survival in pancreatic cancer patients. Patients experienced very few side effects, save local injection site reactions, which was a key consideration for moving the vaccine into trials of healthy individuals.
At Basser, Domchek and colleagues have already completed enrolling cohort A part one and are actively enrolling cohort B. "Soon, we will be vaccinating healthy BRCA1 and BRCA 2 carriers," she said, adding that there "seems to be great interest from healthy carriers who want to come on this study." Cancer vaccines typically have not been tested in early-stage or adjuvant trials, let alone intervention trials for germline mutation carriers who are at high risk of developing cancer, but who do not actually have a diagnosis.
Clinical trials evaluating drugs as a means to prevent or intercept, rather than treat, cancers are challenging and lengthy. Because the endpoints for these trials are often related to whether a patient goes on to develop malignancies far down the line, the trials can take decades or more. For this reason, prevention trials often lack adequate funding and drugmaker support. But researchers like those in Domchek's lab are increasingly determined to tackle them.
The Inovio-UPenn vaccination study is designed to evaluate the cancer vaccine's safety and dose-limiting toxicities as well as antigen-specific immune response over a period of two years, though it will take much longer to show the intervention's ability to prevent cancer development.
"We've considered cancer interception for years, but now I would argue that we actually have the tools to translate it," Domchek said during a plenary session at the meeting on Saturday. "There are multiple viable strategies for non-surgical prevention in BRCA1 or BRCA2 carriers that are being tested or have a good opportunity to be tested."
Because BRCA1 and BRCA2 carriers are at high-risk for a number of the most common malignancies, including breast, ovarian, pancreatic, and prostate cancer, proving the success of an interception strategy could not only have sweeping implications, but also be generalizable to future efforts in other high-risk populations and cancer types, Domchek suggested.
Moving PARPi into the prevention space
Other interventional possibilities could be on the horizon, too, when it comes to breast cancer prevention. For example, Merck and AstraZeneca's PARP inhibitor Lynparza (olaparib) has demonstrated efficacy in the adjuvant treatment setting for early-stage, high-risk breast cancer patients harboring BRCA1 or BRCA2 mutations. The drug recently secured US Food and Drug Administration approval for the adjuvant treatment of HER2-negative, high-risk BRCA1/2-positive breast cancer, based on an event-free survival benefit seen in the large, Phase III randomized OlympiA trial.
As Domchek suggested during her presentation, the fact that the PARP inhibitor has been effective for preventing recurrence following initial treatment for this high-risk, early-stage patient population raises the possibility that Lynparza might be an alternative to prophylactic surgery for healthy BRCA1/2 carriers.
As is the case across much of drug development, Merck and AstraZeneca began by evaluating Lynparza in the metastatic disease setting and then gradually moved the agent into earlier treatment lines from there. "We've gone from metastatic to adjuvant," Domchek said of PARP inhibitors. "Can we go to prevention? I don't know."
She pointed to several early "clues" that the strategy may be worth pursuing. For example, patients in the OlympiA trial who received Lynparza were less likely to develop second primary cancers than patients in the control arm. Indeed, 19 patients receiving Lynparza developed second primary cancers versus 32 patients who received a placebo. The numbers are not statistically significant, and it will take more time to see if the trend continues, but the signal is encouraging, Domchek said.
Within cancer prevention trials it is critical to balance potential benefit against the risk of toxicities. The fact that Lynparza in OlympiA did not appear to cause secondary cancers such as myelodysplastic syndromes or acute myeloid leukemia, as some other treatments do, and had a relatively manageable toxicity profile, is also encouraging for the potential of PARP inhibitors to be used for prevention.
"Compared to placebo [in OlympiA], there was no overall effect on quality of life with olaparib," Domchek added. "There are some differences with nausea and fatigue, but [managing that] is really a question of what should a schedule look like and what is considered tolerable for patients."
"We need to answer many of these questions," she continued. "There are a lot of people thinking about these issues and how we can move forward."
While drugmakers have not announced any concrete plans to evaluate Lynparza as a cancer interception strategy for healthy BRCA1/2 carriers, Domchek seemed to suggest that such a trial does not seem out of the realm of possibilities, especially in light of the high cost and quality-of-life implications of prophylactic mastectomies, oophorectomies, and other such invasive procedures too often presented as the sole option for high-risk BRCA1/2 carriers.
"I admit that large-scale interception studies are difficult, even in high-risk patients," she acknowledged. "They are large, they take a long time … but that does not mean we shouldn't do them. At the end of the day, this is what we want to do: intercept cancers and change people's lives."
https://www.precisiononcologynews.com/cancer/upenn-researchers-enrolling-brca12-carriers-inovio-htert-cancer-vaccine-study?utm_campaign=Precision+Oncology+News+Welcome+Email&utm_medium=email&CSAuthResp=1649718133700%3A0%3A2514068%3A0%3A24%3Asuccess%3A40EC667EE29FABF7195C9F6B1DFF7A91&_ga=2.8889842.658874540.1649717985-1590207770.1649717985&adobe_mc=MCMID%3D58018332632319430302833232159497549527%7CMCORGID%3D138FFF2554E6E7220A4C98C6%2540AdobeOrg%7CTS%3D1649718003&utm_source=Sailthru&CSAuthReq=1#.YlSzeiVHYlQ
“the maker of the Medigen vaccine looked towards the results of the World Health Organization’s Solidarity Trial Vaccines clinical study—a test to evaluate the effectiveness of vaccines around the world. The results are scheduled to be published in early April.” 4/6/22
That should include INO-4800 as well.
psuvanguard.com/medigen-vaccine-controversial-or-helpful/
“Medigen is now waiting for the results of the WHO’s Solidarity Trial Vaccines clinical study, which evaluates the effectiveness of vaccines from around the world.
If the trial proceeds as scheduled, the results are expected by the end of next month or in early April, Medigen chief executive officer Charles Chen said”
taipeitimes.com/News/front/archives/2022/02/16/2003773205
UCSF Brain Tumor Center: This clinical trial will evaluate the safety and efficacy of INO-5401, INO-9012, and cemiplimab, alongside radiation therapy and temozolomide (TMZ), in treating patients with newly diagnosed glioblastoma.
INO-5401 and INO-9012 are comprised of DNA molecules, or plasmids, and are injected intramuscularly and then delivered using electroporation – a technique using electric pulses to push the DNA plasmids into cells. The cells that are electroporated will begin producing specific molecules based on the instructions in the DNA plasmid. For example, cells electroporated with INO-5401 will begin producing antigens that are common in many cancer cells (including WT1, PSMA, and hTERT). Production of these antigens helps activate T-cells to better recognize cancer cells. INO-5401 is therefore considered a T-cell activating immunotherapy.
INO-9012 is another immunotherapeutic agent, a DNA plasmid encoding the human interleukin-12 (IL-12) gene. Cells electroporated with INO-9012 will begin producing IL-12, a protein that promotes the activation of natural killer cells, among other immune-stimulating effects.
Cemiplimab is an antibody-based immunotherapy, administered intravenously, that also targets the immune system and activates it to stop cancer growth and/or kill cancer cells. More specifically, cemiplimab works by binding and inhibiting PD-1, a protein that normally protects the body from attacking itself. Normally, PD-1 works by detecting a molecular signal (called PDL-1) made by various cells across the body. Some cancer cells take advantage of this protection mechanism making the protective signal themselves. Blocking PD-1 with cemiplimab allows the immune system to activate its T-cells and recognize these tumors as cells to be attacked.
Eligible participants will be separated into two cohorts, depending on MGMT promoter methylation status. Both cohorts will receive the INO-5401, INO-9012, and cemiplimab at the same doses and schedule, in addition to radiation therapy and TMZ, if clinically indicated:
Experimental Cohort A (Unmethylated MGMT Promoter): INO-5401 + INO-9012 + Cemiplimab + RT + TMZ
Experimental Cohort B (Methylated MGMT Promoter): INO-5401 + INO-9012 + Cemiplimab + RT + TMZ
Actual Study Start Date :
May 31, 2018
Estimated Primary Completion Date :
June 30, 2022
Estimated Study Completion Date :
June 30, 2022
21 study locations
United States, California
City of Hope
Duarte, California, United States, 91010
Stanford University, School of Medicine
Palo Alto, California, United States, 94304
University of California, San Francisco
San Francisco, California, United States, 94143
United States, Florida
University of Miami - Sylvester Comprehensive Cancer Center
Miami, Florida, United States, 33136
Moffitt Cancer Center
Tampa, Florida, United States, 33612
United States, Georgia
Emory University School of Medicine
Atlanta, Georgia, United States, 30322
United States, Massachusetts
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02215
United States, Michigan
Henry Ford Health System
Detroit, Michigan, United States, 48202
United States, New Jersey
Rutgers University - Cancer Institute of New Jersey
New Brunswick, New Jersey, United States, 08901
United States, New York
New York University Langone Medical Center; Perlmutter Cancer Center
New York, New York, United States, 10016
Icahn School of Medicine at Mount Sinai
New York, New York, United States, 10029
Columbia University Medical Center The Neurological Institute of New York
New York, New York, United States, 10032
New York-Presbyterian Hospital/Weill Cornell Medical Center
New York, New York, United States, 10065
United States, North Carolina
University of North Carolina School of Medicine
Chapel Hill, North Carolina, United States, 27599
United States, Oklahoma
Stephenson Cancer Center
Oklahoma City, Oklahoma, United States, 73104
United States, Oregon
Oregon Health & Science University
Portland, Oregon, United States, 97239
United States, Pennsylvania
University of Pennsylvania Health System: Penn Medicine
Philadelphia, Pennsylvania, United States, 19104
UPMC Cancer Center Neuro-Oncology; UPMC Cancer Pavilion
Pittsburgh, Pennsylvania, United States, 15232
United States, Texas
Texas Oncology
Austin, Texas, United States, 78705
Baylor College of Medicine
Houston, Texas, United States, 77030
United States, Utah
Huntsman Cancer Institute
Salt Lake City, Utah, United States, 84112
Monday, April 04, 2022, at 18:53- Colombia Conducts Trials to Determine Effectiveness of New COVID-19 Vaccine. The World Health Organization (WHO) has been working with a group of experts in order to select from all the vaccines that are in phases of research I and II, those that have the greatest results in efficacy and safety. "The objective has been to be able to carry out a trial that allows them to be compared with each other and to have immunizers that are effective towards variants of the virus that are now and that may appear later," Carlos Álvarez, national coordinator of studies on COVID-19 in Colombia, said on previous occasions. The Ministry of Health and Social Protection (MinSalud) has announced that it is accompanying the study in eight cities in the country. Many of the current vaccines are found with patents that do not allow their adequate distribution in the world. It should be remembered that, the WHO has been developing a vaccine to bring it to the world in an equitable way. In this way, once we are all vaccinated, this pandemic can be terminated. Likewise, the Clinical Study 'Vaccine Solidarity' is being evaluated in the eight cities of the country evaluating through volunteers, how safe the new vaccines against COVID-19 are, with the accompaniment of MinSalud. "This new vaccine is safe. It has been verified with most of the participants we have had in Bogotá. Of 80 people, some have had a headache or malaise that resolves spontaneously. We have had no serious or severe adverse effects. And no one has had to be taken to the emergency room," said Freddy Carreño, a researcher at the Solidarity Study.
12/15/21 Inovio vaccine arrives in Veracruz, with immunity in 24 hours
from the 1st dose
The biological Inovio arrives in Veracruz as a high-tech and effective alternative against Covid-19, for this reason, Training for Comprehensive Consulting for the Clinical Research Center (FAICIC) will have 250 antigens to apply to the same number of 18-year-olds in forward that they have never been vaccinated against the coronavirus, nor are they pregnant or currently breastfeeding; as well as those who suffer from chronic diseases such as: diabetes, hypertension, cancer, HIV, obesity, allergies, among others.
The general director of the Faicic Clinical Research Center, Sharzy Molina Guízar, explained that it is a very safe antigen, which has the characteristic that it is not injected, but through a shot in the arm that will impact at the cellular level, through a electrode, since it has a very different molecular composition that makes it different from those already known, because it travels at the cellular level, causing immunity in 24 hours, for longer and with greater efficiency.
“Previous vaccines were given through an injection in the arm; this also goes on the arm, but it is done by means of a device that is like a small pistol, which what it does is that here in the arm, in the muscle, a shot is fired that does not cut, that does not open the skin, it does not hurt, it is painless and this allows it to travel to the cellular level and how is it that we achieve immunity in 24 hours? We achieve it because it travels so fast in the cells that what it does is reproduce, they cause an excitation to the cells that makes one infect the other very quickly and, then, we can go from one to 10, from 10 to 100 , from 100 to a thousand and not only do we cause immunity for a longer time, but also, much more effectively”.
He explained that Inovio decided to do it this way, since the existing vaccines that are applied in the injected arm, their route at the muscular level generated immunity from 28 to more than 40 days, depending on the organism, due to its composition and its journey in the body, which also caused other allergic reactions or altered some parts of the body, while Inovio causes immediate immunity.
Likewise, Molina Guízar recognized that, based on studies carried out, Inovio has proven high efficacy against the Omicron variant, although investigations continue, so it is added to the list of qualities of this antigen.
“This vaccine, so far, is showing an efficacy of 95.5% in the first application that is given at 24 hours. This vaccine consists of two doses (two applications): on day zero, which is the day the vaccine is applied, and on day 28”, stated the interviewee.
The general director of Faicic admitted that there are side effects similar to those of injected vaccines, such as: headache, nausea, dizziness, weakness, fever, among others, which are treatable and will be treated by the medical staff of the center of research.
In this sense, he recognized that there is still a large amount of population not vaccinated against this disease for various reasons, such as: fear, resistance, lack of information, among others.
“After two years, we already have a lot of experience, we have seen how to improve it and we invite the population that was afraid to come because now we have a very safe vaccine; It is also aimed at those people who, for example, are allergic, who have chronic-degenerative diseases”.
Sharzy Molina highlighted that they will be working every day for the Inovio application, including holidays such as December 25 and January 1, 2022, for which she invited citizens with these characteristics to sign up for this application, since It will serve the population of Veracruz and foreigners, where in the case of the latter, they will be supported with the transfer, therefore, they require social leaders who support with this process the population of marginalized areas whose expenses are assumed by Faicic.
He added that in addition to the support for the transfer to the Faicic headquarters, patients will be provided with: medical, nutritional, psychological consultation, laboratory studies and for a year and a half they will remain in contact with them, with open consultation for any symptom or subsequent condition that they may present.
He recalled that Faicic is a research center that seeks to improve people's health and lives, through studies and in coordination with recognized pharmaceutical companies.
https://www-eldictamen-mx.translate.goog/noticias-de-veracruz/boca-ver/llega-a-veracruz-vacuna-inovio-con-inmunidad-en-24-horas-desde-la-1a-dosis/?_x_tr_sl=auto&_x_tr_tl=en&_x_tr_hl=en
4/4/22 Prime-boost vaccination regimens with INO-4800 and INO-4802 augment and broaden immune responses against SARS-CoV-2 in nonhuman primates
Inovio Pharmaceuticals, Plymouth Meeting, PA, 19462, USA
Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA, 19104, USA
Received 2 November 2021, Revised 2 March 2022, Accepted 23 March 2022, Available online 4 April 2022.
Abstract
The enhanced transmissibility and immune evasion associated with emerging SARS-CoV-2 variants demands the development of next-generation vaccines capable of inducing superior protection amid a shifting pandemic landscape. Since a portion of the global population harbors some level of immunity from vaccines based on the original Wuhan-Hu-1 SARS-CoV-2 sequence or natural infection, an important question going forward is whether this immunity can be boosted by next-generation vaccines that target emerging variants while simultaneously maintaining long-term protection against existing strains. Here, we evaluated the immunogenicity of INO-4800, our synthetic DNA vaccine candidate for COVID-19 currently in clinical evaluation, and INO-4802, a next-generation DNA vaccine designed to broadly target emerging SARS-CoV-2 variants, as booster vaccines in nonhuman primates. Rhesus macaques primed over one year prior with the first-generation INO-4800 vaccine were boosted with either INO-4800 or INO-4802 in homologous or heterologous prime-boost regimens. Both boosting schedules led to an expansion of T cells and antibody responses which were characterized by improved neutralizing and ACE2 blocking activity across wild-type SARS-CoV-2 as well as multiple variants of concern. These data illustrate the durability of immunity following vaccination with INO-4800 and additionally support the use of either INO-4800 or INO-4802 in prime-boost regimens.
https://www.sciencedirect.com/science/article/pii/S0264410X22003681
(Repost) Summary by @StockHound Posted on November 01, 2021.
"In short, compared to our competitors, 4802 as a booster is displaying amazing numbers. No wonder why the WHO has chosen as 1 of 2 vaccines in the Solidarity trial.":
Here's my take on the article from BioRxiv on the INO-4800 and INO-4802 boosters.
Inovio originally conducted a Pre-Clinical study on Mice and Guinea Pigs to advance to P1 human trials. They also did a study on Non-Human Primates Rhesus Macaques monkeys. These monkeys elicit similar immune responses as humans do. During this study they found the following antibody responses:
• GMT Binding Antibodies = 258,032 @ 6 weeks (Convalesent (Covid Recovered patients) had a GMT BA = 142,140)
• GMT Neutralizing Antibodies = 175 @ 6 weeks (Convalesent had an approx. GMT NA = 150)
These numbers were also seen in the Phase 2 clinical trials using the 2 mg dose. It's noted that the Binding Antibody measurement had changed at this point, unfortunately it will be hard to compare to other vaccines providers at this point. I'm concluding that since the neutralizing antibodies were similar between the monkey study and P2, I can assume that Binding Antibodies of 258,032 from the monkey study should be close to the Binding Antibodies of P2 of 2210. INO 4800 P2 results:
• GMT Binding Antibodies = 2210
• GMT Neutralizing Antibodies = 150
Neutralizing Antibodies of a Convalesent patient was nearly 150 and Binding Antibodies of 142,140. Comparing to mRNA vaccines at this time, their GMT NA was about 343-900 (MRNA). MRNA also produced GMT Binding Antibodies of 782,719 for the 100ug dose.
Coming back to the most recent booster article, here are the numbers at weeks 43-64, essentially 1 year since the 2nd dose on these monkeys.
4800:
• GMT Binding Antibodies: Wild Card=3077, Beta=2338, Gamma=2077, Delta=21,044
• GMT Neutralizing Antibodies: Wild Card=2286, Beta=1199, Gamma=1596, Delta=785
4802:
• GMT Binding Antibodies: Wild Card=6285, Beta=6285, Gamma=6285, Delta=6285
• GMT Neutralizing Antibodies: Wild Card=3712, Beta=1452, Gamma=4389, Delta=1434
It is controversial which antibody is more important as both have an important role within the immune system and response to a pathogen. Neutralizing antibodies defend the cell and can result in lifelong immunity to the target infection. Binding Antibodies bind to the pathogen and trigger the immune system to attack it with white blood cells.
What this article is telling me, boosting the INO-4800 as a primary vaccine with either INO-4800 or INO-4802 as a booster 1 year later shows significant increases in Neutralizing Antibodies especially with INO-4802 and increase in Binding Antibodies well past what Convalescent patients have displayed. The significantly higher number Neutralizing antibodies providing an advantage to long term protection. It's worth noting that mRNA vaccine booster will also increase their Neutralizing Antibodies to an approximate GMT of 2000 or 800 for Delta. Though these numbers are similar to INO, it is good in the fact that we can achieve the same and slightly better results of a leading EUA vaccinev while providing a superior safety profile, thermo stability and shelf life.
This also doesn't include INO advantage with the production and sustainment of T, B, CD4 and CD8 cells.
In short, compared to our competitors, 4802 as a booster is displaying amazing numbers. No wonder why the WHO has chosen as 1 of 2 vaccines in the Solidarity trial.
World Vaccine Congress Washington 2022, WASHINGTON DC, Apr 21 09:40
Inovio’s DNA COVID vaccine update
COVID & Beyond - M4, Independence Salon D
Joseph Kim,Chief Executive Officer, Inovio Pharmaceuticals
Apr 18 14:00
ANTIBODIES FOR INFECTIOUS DISEASES 2pm - 5pm - M4, Liberty Salon O
ANTIBODIES FOR INFECTIOUS DISEASES - Liberty Salon O
Mark Esser,Vice President, Early Vaccines and Immune Therapies, AstraZeneca
Flonza Isa,Associate Medical Director, Regeneron Pharmaceuticals
Alina Baum,Director, Infectious Diseases, Regeneron Pharmaceuticals
Apr 20 09:00
Chair’s opening remarks
Emerging and Infectious Diseases - M4, Liberty Salon M
David Weiner,VP, Director of Vaccine & Immunology Center, The Wistar Institute
Apr 21 11:30
GT-EPIC platform to target advanced hepatocellular cancer in a patient specific manner
Cancer and Immunotherapy - M4, Liberty Salon I-K
Niranjan Sardesai,President & Chief Executive Officer, Founder, Geneos Therapeutics
Apr 20 17:10
Panel: Advances in our understanding of the key parameters of tumor epitope immunogenicity
Cancer and Immunotherapy - M4, Liberty Salon I-K
Niranjan Sardesai,President & Chief Executive Officer, Founder, Geneos Therapeutics
Apr 20 17:10
Panel: What are the risks to self-spreading viruses?
Veterinary - M4, Supreme Court Room
Stanley Plotkin,Emeritus Professor, University of Pennsylvania School Of Medicine
3/28/22 Geneos Therapeutics, a clinical stage biotherapeutics company spun out of Inovio Pharmaceuticals, raised $17 million in a private stock sale.
The 6-year-old Plymouth Meeting company's Series A2 financing was led by Flerie Invest, a European venture capital firm based in Stockholm and London that specializes in backing life sciences companies tackling major medical challenges. Existing Series A investors Santé Ventures, Korea Investment Partners Global Bio Fund, and Inovio (NASDAQ: INO) also participated. Geneos closed its initial $12 million Series A round in March 2021.
Geneos plans to use the bulk of the proceeds to expand the clinical trials for its lead new drug candidate GNOS-PV02 from 24 to 36 patients. The personalized cancer vaccine is under development as a treatment for patients with advanced hepatocellular carcinoma, a type of liver cancer.
The experimental treatment is a tumor-specific DNA plasmid-based product that is designed and manufactured for each patient based on their unique tumor mutations. The mutations are identified by sequencing each patient’s tumor. The company's GT-EPIC platform targets unique neoantigens or abnormal mutations produced by cancer cells.
The investment money will also be used to expand the company's pipeline into a new, undisclosed cancer indication. The remaining funds will be used for general company operations.
In February 2021, Geneos completed a second closing of the Series A-1 preferred stock financing, in which the Company did not participate. Following this transaction, the Company held approximately 35% of the outstanding equity, on an as-converted to common stock basis.
The Company continues to exclusively license its SynCon® immunotherapy and CELLECTRA® technology platform to Geneos to be used in the field of personalized, neoantigen-based therapy for cancer. The license agreement provides for potential royalty payments to the Company in the event that Geneos commercializes any products using the licensed technology. The Company is not obligated to use any of its assets to fund the future operations of Geneos.
“I think INO will become the standard of care for glioblastoma patients. If we’ve already extended the lives of methylated glioblastoma patients by AT LEAST 6 months median (that is what we know so far and the study is not yet over).
13,000 people diagnosed with GB each year and I know for a fact Keytruda costs $125,000 per year per patient. So if patients are living AT LEAST 2.5 years that is 32,500 patients being treated per year x $125,000 potential revenue per year (maybe we would even charge more since our treatment is more effective than what is currently being used). That is an extra $4 billion per year in revenue. That also only takes care of USA patients.
$4 billion per year revenue x .20 profit margin x 35 (PE ratio) = over $16 billion to our market cap. That’s a 10x return only for one product.” By JuliekLily5410
Patients can apply for Compassionate Use with FDA to get 5401 GBM treatment immediately.
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
INO closed up 5.85% at $3.8 on 4/1. Able to find support at 50-dma. Bullish!
50-Day $3.52
100-Day $4.77
200-Day $6.40 likely tested in 2Q22
2Q22 Catalysts:
? Advaccine’s Homologous and Heterologous pGx9501 booster 2,4,6,8 wks Interim Readout. EUA. Preorder.
? WHO’s STV Interim Readout. Apply EUL. COVAX preorders.
? INNOVATE resumes in Philippines ????, Colombia ????, Brazil ????, Mexico ???? , starts in India ????, Rwanda ????, Tunisia ????, Thailand ????
? RRP 3107 P3 IND approval
? GBM 5401 OS36, median OS MGMT-methylated
? COVID-19 dMAb® P1 starts in May
AZD5396, AZD8076
? Report INO-4500 Lassa P1b data
“We believe this is an important
step for dMAb program. This has to do with announcement we had made in December 2020 regarding dMAbs to treat Covid19. We are working with many collaborators on this project as you know. We are hoping that this can lead to benefits not just for Covid but for our dMAbs program, in general.
Thank you
Investor Relations” 3/25/22
STV Primary outcome measure:
Virologically confirmed COVID-19 disease, through SARS-CoV2 RNA isolation and RRT-PCR amplification in oro-nasopharyngeal specimen, regardless of disease severity, at 14, 180, 365 days after the last dose.
isrctn.com/holding
INNOVATE primary endpoint changes from prevention of virologically confirmed COVID-19 disease to prevention of severe disease due to COVID-19.
Before the amendment, INNOVATE was a duplicate of STV. In the Omicron BA-1 and BA-2 era, all other vaccines have much lower infection prevention efficacy.
3/1 Hartaj Singh: Sanofi and GSK reported a vaccine efficacy of 58%, right? And they ended their trial before Omicron really hit. They’re looking for approval. Their severe disease endpoint looked pretty good. Moderna’s already talking about bivalent vaccines against Omicron.
So, it seems you’re getting proactive in trying to get ahead of what Omicron can do to current vaccines in development or approvals.
How are you thinking if you were to get that protocol amendment? Would you essentially market the vaccine on that disease severity endpoint, hospitalization endpoint, plus the risk benefit profile, the actual product profile of the vaccine?
Dr. Joseph Kim
Yes. Hi Hartaj, absolutely. That’s the view that we have. Obviously, the Omicron has thrown a curveball to all vaccine developers, with reduction in antibody responses from the original ancestral strain targeted vaccine, which, all of the approved vaccines and some of the ones in testing, including INO-4800 is. 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.
Hartaj Singh
Yes, great. Joe, I mean, your in vitro data matches up pretty well against some of the commercial and vaccines in approval.
3/15 Hartaj Singh: Any updates on 4802 timeline? Any updates on the S. Korea trial?
JK: That was the 4800 P1. They were completed. And they were P1 trials. So, both P1 trials in S. Korea and China had results similar to our U.S. trial. It was a similarly or identically designed trial. So, we published under U.S. We would also look to publish those results along with our collaborators IVI in S. Korea and in China. We are in P3, so a lot more interest in the later stage program.
For 4802, 4803, we have a pan Covid program that we have published, completed the preclinical trials. We put the pause in 4802 in clinic, just b/c 4800 was so cost effective, both in the animal testing and clinical sample testing compared to 4802. Of course, the Omicron changed - it was a big shift until Omicron. And now we have an Omicron match construct, that’s being tested preclinically.
So, there are many research constructs that we have designed. But our lead horse is 4800. We think we have a vaccine that can provide protection across all different variants in protecting against severe diseases. And we look forward to testing that thesis from our INNOVATE trial but also demonstrate 4800’s ability to serve as a booster.
The as we develop out COVID-19 platform, once we get our first product approved, we would be able to utilize the bridging strategy that many regulators have been deploying to bridge into the new variants as necessary. But our current focus is really in getting 4800 tested and approved through emergency and full approval where appropriate.
“It is my understanding that Advaccine is reengaging the IPO pathway. I also believe they will be able to share data on their boost trial in not too distant future since enrollment had been completed.
Thanks
Investor Relations” 4/2/22
Key 2021 Company highlights included:
• Completed dose selection from Phase 2 data and initiated global Phase 3 trial for INO-4800, our COVID-19 vaccine candidate;
• INO-4800 selected by the World Health Organization ("WHO") to be included in Solidarity Trial Vaccines;
• Established manufacturing consortium and developed a proprietary manufacturing process for production of plasmids
• Presented efficacy data for REVEAL1 (cervical dysplasia) and completed enrollment for REVEAL2 (confirmatory trial) Phase 3 trials for product candidate VGX-3100;
• Identified and advanced the development of pre-treatment biomarker for VGX-3100;
• Presented additional efficacy data for product candidate INO-5401 + cemiplimab in glioblastoma multiforme (GBM) participants;
• Completed enrollment for recurrent respiratory papillomatosis ("RRP") Phase 1/2 clinical trial (product candidate INO-3701);
• Completed enrollment for infectious disease vaccine programs: Phase 1b clinical trial for Lassa fever (INO-4500),Phase 1b clinical trial for Ebola (INO-4201 as a booster), and the first portion of Phase 2 clinical trial for MERS (INO-4700); and
• Advanced Zika dMAb trial with side-port needles.
2020 Performance-Based PSUs: Rigorous Milestone Goals for COVID-19 Vaccine Candidate
The 2020 PSUs, which were intended to cover a multi-year performance period, have performance conditions related to the development and commercialization of INO-4800, our vaccine candidate for COVID-19. Given the multi-year nature of the goals described below, performance has not yet been achieved and will continue to be assessed through the full performance period.
Portions of the PSUs will only vest, if at all, upon the achievement of:
• full enrollment in our planned Phase 2/3 trial of INO-4800;
• non-dilutive, third-party funding for clinical development and manufacturing of INO-4800;
• manufacture of 100 million doses of INO-4800 and a specified number of delivery devices; and
• U.S. FDA approval, with no more than a specified number of other COVID-19 vaccines having previously received such approval. The target achievement date for each of the goals is within three years from the grant date in August 2020.
Annual Cash Incentive: Rigorous, Pre-Set Clinical, Regulatory and Corporate Goals, Strong Performance Achievement and Annual Incentive Plan Payouts Reflecting Pay for Performance Alignment
COVID-19 Vaccine Candidates:
• 15% for completing dose selection from Phase 2 data and initiating the global Phase 3 trial for INO-4800;
• 12% for advancing INO-4802 addressing variant of concern and conducting a Phase 1/2 trial for INO-4800; and
• 8% for manufacturing of DNA plasmid, devices and arrays to deliver INO-4800 and INO-4802.
VGX-3100:
• 12% based on presentation of top line efficacy data for our REVEAL1 Phase 3 trial;
• 12% based on enrollment levels and numbers of patients dosed in our REVEAL2 Phase 3 trial; and
• 6% for advancing the development of the miRNA biomarker in vitro diagnostic ("IVD") platform with Qiagen and analyzing the research level data of REVEAL 1 clinical samples for miRNA signatures.
Advancing Oncology Programs:
• 6% to conduct additional efficacy and tolerability assessments and conduct clinical data review with Regeneron for GBM-001; and
• 6% based on enrollment levels and numbers of patients dosed in our RRP trial.
Advancing Infectious Disease Programs:
• 4% for development activities associated with our Zika dMAb trial; and
• 6% in the aggregate based on enrollment and numbers of patients dosed in our Lassa fever and MERS trials.
Additional Corporate Objective:
• 13% to maintain a strong balance sheet via a combination of new funding and control of expenses to end the year with no less than 2 years cash runway based on the current approved budget.
In 2021, our performance against the corporate objectives resulted in a corporate score of 96.4%, calculated as follows, compared to a 2020 corporate performance score of 110%.
• We partially met the goals surrounding INO-4800 and INO-4802, collectively yielding 24% credit of the possible 27%;
• We partially met the goals surrounding the manufacturing of DNA plasmid, devices, and arrays, yielding 5% credit of the possible 8%;
• We achieved our goals with respect to REVEAL-1 Phase 3 efficacy data readout target and REVEAL-2 Phase 3 dosing target, collectively yielding 24% credit;
• We exceeded our goal to advance the development of the miRNA biomarker IVD platform, yielding 7.5% credit (which was 125% of the target weighting of 6% credit);
• We achieved our goal for GBM-001, yielding 6% credit;
• We exceeded our goal surrounding RRP-001 dosing, yielding 7.5% credit (which was 125% of the target weighting of 6% credit);
• We successfully submitted a proposed amendment to the RRP Phase 3 trial design, yielding 2% credit;
• We partially met our goal for Lassa fever trial dosing, yielding 1.5% credit of the possible 3%;
• We significantly exceeded our goal with respect to MERS dosing, yielding 4.5% credit (which was 150% of the target weighting of 3% credit;
• We met our goal related to the Zika dMAb trial, yielding 4% credit; and
• We partially met our other corporate objectives, yielding 10.4% credit of the possible 13%.
4/1/22 DNA-based, needle-free Covid vaccine ZyCoV-D 67% effective in Phase 3 trial, Lancet study finds
Vaccine ZyCoV-D contains a small DNA molecule that can replicate independently; it does not need a SARS-CoV-2 virus strain.
New Delhi: The phase 3 clinical trial of the world’s first DNA-based vaccine ZyCoV-D have shown that the needle-free, three-dose vaccine has an efficacy of 66.6 per cent, according to the results published Friday in The Lancet journal.
Although Indian regulatory authorities have approved Zydus Lifesciences’ (formerly known as Cadila Healthcare) ZyCoV-D for children over 12, the vaccine is yet to be rolled out in the country.
Developed in 2020, preliminary animal study demonstrated that the vaccine induces antibody response including neutralising antibodies against SARS-CoV-2. Subsequent phase 1 and phase 2 trials in 1,048 human volunteers found the vaccine to be safe.
The vaccines contain a genetically engineered plasmid — a small DNA molecule that can replicate independently. The plasmid is engineered to produce the spike protein of the virus, which then triggers a protective immunological response.
DNA-based vaccines do not need a SARS-CoV-2 virus strain, unlike the inactivated vaccines that require viruses in killed or inactivated forms. This makes developing the virus much simpler as it can be manufactured under minimal biosafety requirements.
In the absence of any infectious agent in the vaccine, it can be manufactured with ease, under minimal biosafety requirements (BSL-1).
ZyCoV-D is delivered using a needle-free injection device.
The trial of the vaccine, conducted in India, is the first phase 3 trial globally to deliver a DNA vaccine using a needle-free delivery device, and the first time that a COVID-19 vaccine is being tested in the age group of 12–17 years in India.
Overall, the study demonstrated that intradermal injection of ZyCoV-D vaccine is safe and feasible and might achieve successful prevention of COVID-19 diseases in a large population.
“Additionally, the DNA vaccine is based on a plasmid DNA platform, which allows rapid generation of new constructs; the ZyCoV-D vaccine can therefore pave the way for next-generation DNA vaccines capable of handling mutant strains,” the authors wrote in their study.
“We anticipate that the major implication of this study will be the introduction of DNA-based prophylactic therapy against highly infectious diseases such as SARS-CoV-2,” they said.
The study showed that a three-dose regimen of ZyCoV-D, administered intradermally via a needle-free injection system, was found to be 66.6 percent effective against Covid-19.
The study was conducted during the peak of the second wave of COVID-19 in India, which was mainly due to the B.1.617.2 (delta) variant.
As many as 27,703 volunteers participated in the trial, of which 13,851 were given the vaccine, while the rest were given a placebo.
The team, which included doctors from Grant Government Medical College, Sir J J Group of Hospital in Mumbai, N R R Hospital in Bangalore, and Cadila Healthcare, conclude that the ZyCoV-D vaccine is effective against the delta variant.
“Considering that no severe or moderate COVID-19 cases were reported in the ZyCoV-D group, and based on the interim analysis results, the vaccine was found to be 100% effective against severe and moderate COVID-19 cases and 64·9% effective against mild COVID-19 cases,” the researchers said.
“Therefore, it is possible that the severe and moderate cases that might result in fatalities and put enormous pressure on health-care systems could be prevented to a great extent with full vaccination using the ZyCoV-D vaccine,” according to the study.
https://theprint.in/health/dna-based-needle-free-covid-vaccine-zycov-d-67-effective-in-phase-3-trial-lancet-study-finds/897941/
SHANGHAI, April 1 (Reuters) - China's commercial hub of Shanghai ground to halt on Friday after the government locked down most of the city's 26 million residents to stop the spread of COVID-19, even as official numbers put local cases falling for the second day in a row.
The city government late on Thursday extended an existing lockdown in eastern districts, just as western parts of the city were shut down as scheduled.
Fresh official guidance indicated that many in China's most populous city will now be required to stay home as long as it takes to control the outbreak - instructed not to cross their doorsteps even to dispose of rubbish or walk their dogs.
The lockdown, designed to stop an outbreak of the highly transmissible Omicron variant that started about a month ago, began on Monday and was originally due to last 10 days in total.
Areas east of Shanghai's Huangpu River were to be closed for five days, before reopening as western districts began a five-day shutdown.
But the city government said it would lift the curbs in east Shanghai in stages instead. read more
This means the majority of districts are now under a lockdown that covers the office towers of the Lujiazui district, China's answer to Wall Street, and factories including Volkswagen's (VOWG_p.DE) joint venture with SAIC Motor (600104.SS) and U.S. automaker Tesla's (TSLA.O) plant.
https://www.reuters.com/world/asia-pacific/shanghai-expands-covid-lockdown-life-hold-city-26-million-2022-04-01/?utm_source=Sailthru&utm_medium=newsletter&utm_campaign=global-healthcare&utm_term=Health%20Report%20-%202021%20-%20Master%20List
April 1 (Reuters) - Russia's total number of COVID-related deaths have reached almost 778,000 since the start of the pandemic in April 2020, Reuters calculations based on new data from the Rosstat state statistics service showed on Friday.
Rosstat said that 43,201 people had died from COVID or related causes in February, up from 35,807 in January.
The death toll hit a record monthly high of nearly 90,000 in November, propelling Russia into second place for the highest number of fatalities worldwide after the United States, which has more than twice the population. read more
Reuters calculations also showed Russia recorded more than 958,000 excess deaths since the beginning of the pandemic in April 2020 to the end of February, when compared to average mortality in 2015-2019.
Some epidemiologists say that calculating excess deaths is the best way to assess the true impact of a pandemic.
https://www.reuters.com/world/europe/russias-total-number-covid-related-deaths-hits-nearly-778000-2022-04-01/?utm_source=Sailthru&utm_medium=newsletter&utm_campaign=global-healthcare&utm_term=Health%20Report%20-%202021%20-%20Master%20List
$10M C2K Procurement Contract will be recognized as revenue, 100% margin in 1Q22, or 2Q22
10-K, pg 97: Additionally, in June 2020, the Company was awarded a fixed-price contract (the “Procurement Contract”) from the DoD for the purchase of the Company’s intradermal CELLECTRA 2000 device and accessories. The CELLECTRA 2000 devices will be used to inject INO-4800 in the Company’s later-stage clinical trials. The total purchase price under the Procurement Contract is expected to be approximately $10.7 million. As of December 31, 2021, the Company determined that the Procurement Contract falls under the scope of ASC Topic 606 as the contract is with a customer and the Company is able to satisfy its obligations under the arrangement as the Phase 3 clinical trials of INO-4800 are underway. Performance obligations under the Procurement Contract consist of the delivery of a specified number of CELLECTRA® 2000 devices and accessories. The total transaction price was allocated to the individual performance obligations based on the determined standalone selling price for the devices and accessories. The Company will recognize revenue on the consolidated statement of operations upon shipment of the purchased devices and accessories. During the year ended December 31, 2021, the Company recorded revenue of $755,000 from the Procurement Contract. This revenue was recognized at a 100% margin as the sale was for products whose related inventory had previously been written down to zero.
Upon good STV Iterim Readout which meets or exceeds Primary Endpoint 50% efficacy of prevention of virologically confirmed COVID-19 disease, even before WHO granting EUL, Ino can start talking to LMICs for 4800, C2K Pre-orders. The WHO will quickly grant EUL as they OWN trial data.
pGx9501 booster EUA may trigger large Biologic, device orders in China and from Chinese government for Vaccine Diplomacy.
In April 2021, the Company announced that the DoD had notified the Company that it will discontinue funding for the Phase 3 segment of the Company's clinical trial of INO-4800 in the United States, while continuing funding under the OTA Agreement and Procurement Contract.
3/1 JK: “STV is run and sponsored by the WHO. They have full control. 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.
Vaccine homologous and heterologous boost trials, that’s fully enrolled. Advaccine expects to have data in the second quarter of this year.”
3/6/22 Expect STV Interim Readout April 2022. “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.
Under the OTA Agreement, the Company intends to develop the CELLECTRA 3PSP device and arrays for use in the U.S. military population and the U.S. population as a whole, subject to approval of the device by FDA. The OTA Agreement is also expected to support large-scale manufacturing of the CELLECTRA
3PSP device, as well as large-scale DNA plasmid production for manufacture and supply of a specified number of doses of INO-4800 in support of FDA approval of the device. The total amount of funding being made available to the Company under the OTA Agreement is $54.5M. The Company will record contra-research development expense on the consolidated statement of operations in the same period that the underlying expenses are incurred.
https://mb.com.ph/2022/03/06/7083-participants-of-who-solidarity-trials-get-first-dose-of-covid-19-jabs/
http://www.chictr.org.cn/showproj.aspx?proj=131321&fbclid=IwAR1AVdMvFu74Nx8-pOSgRo4VjZMy7l0knDclViZlyOK_rPbfPJwTi2OfN64
Cellectra 3PSP, is handheld and battery operated. It can deliver about a hundred doses on a single charge and has a life-span of about 5,000 uses, due to battery limitations.
50K*5K=250M doses. EUL requires a sufficient device quantity For COVAX. So does China EUA.
Each use requires a disposable tip. As with more conventional vaccines, the injection site is the upper arm. Vaccination starts with an intradermal injection of the vaccine dose?a shot that's only skin deep. Then, the tip of the Cellectra device is pressed against the skin, directly over the location of the shot. Electrodes about 3 mm in length administer a series of four square-wave electrical pulses that last 42 milliseconds each, at 0.2 amperes.
The recipient feels a brief twinge, similar to the level of pain people experience from a flu shot. Recipients rated it at an average of about 2.5 on a 0-to-10 pain scale?although the feeling is said to be like a buzzing sensation, rather than the prick and pressure of a shot.
The pulses cause nearby cells to temporarily open channels through which the vaccine can enter. As soon as the electrical pulses finish, those channels close. “Now this DNA molecule is trapped inside the cells," says Inovio's Broderick. The DNA then “acts like a code, so your cells become a factory for producing the vaccine," she explains. Electroporation is generally 10 to 100 times as efficient at provoking an immune response as the same DNA vaccine given by a conventional needle injection alone, says Lu of the University of Massachusetts.
Over the last decade, Inovio's DNA vaccines have been tested against HIV, Ebola, MERS, Lassa fever, and human papillomavirus (HPV), each delivered with some form of electroporation. In total, more than 3,000 people have received one of Inovio's electroporated medicines, largely through phase 1 and 2 studies, Broderick says.
https://spectrum.ieee.org/inovios-electrical-device-zaps-a-covid19-vaccine-into-the-body
3/15 JK at Oppenheimer: “We are gearing up our CELLECTRA 3PSP both for regulatory approvals, but also for our potential emergency use. Once our INNOVATE and SOLIDARITY trials, once we can demonstrate efficacy and safety, of course, our endgame is to apply for emergency approval and then the full approval.
So, we have been solving the scaling up of device manufacturing. It’s one of those platform things. It does slow us down of our clinical device from going from P1, P2, P3 for COVID vaccine. But we have solved for these issues. And the beauty of this platform is that once you solve for them, you don’t have to deal with the same issues again. So, our inventories are very strong.
We have CELLECTRA 2000 that we are using for our clinical trials. We have extensive inventory to execute all of our trials, including COVID-19. We have CELLECTRA 5PSP that is currently being used in REVEAL1 and REVEAL2.
We have also used them in some of our Vulvar trial as well in P2. And we have plenty of inventory. We are actually gearing up commercial inventory, studying that as we prepare to wrap up REVEAL2 and potentially have the package in preparation for our feature commercialization.“
Plumline Approval of Phase 3 Plan for Dog DNA Immunotherapy
Aim to reduce recurrence rate by combining chemotherapy and 'PLS-D5000' for blood cancer in dogs Reporter Lim Jeong-yo | Public 2022-03-24 13:59:27
This article was published on March 24, 2022 at 13:59 The Bell Paid Page .
Plumline Life Sciences announced on the 24th that the Ministry of Agriculture, Food and Rural Affairs has approved the Phase 3 clinical trial plan for 'PLS-D5000', a DNA immunotherapy for dogs.
In this phase 3 clinical trial, Plumline Life Sciences will confirm the efficacy and safety of PLS-D5000 against malignant lymphoma (hematologic cancer).
Malignant lymphomas are caused by malignant changes in lymphocytes in the lymphoid tissues constituting the immune system. If left untreated, the dog dies within 3-4 months.
Currently, the most preferred treatment modality is CHOP combination chemotherapy (vincristine, doxorubicin, cytoxane, L-asparaginase, and prednisone), but only temporary tumor remission is possible. The majority of cases recur, and even if they gradually fail to respond to chemotherapy and receive treatment, the average dog survives for about 12 months.
PLS-D5000 is a dog-only DNA immunotherapy that targets the TERT protein, which is overexpressed in 90% of canine cancers. The company explains that it can strongly induce cellular immunity that can attack and kill malignant blood cancer as it has been developed as a platform technology that is differentiated compared to the previously known dog breed TERT DNA. Unlike chemotherapy, which is a cytotoxic substance, the possibility of side effects is very low and it can be used continuously.
According to an IRBM oncology paper, when TERT DNA immunotherapy and chemotherapy are combined, the total survival period is extended by more than 250% (100 weeks vs 40 weeks) compared to conventional chemotherapy.
Since dog lymphoma is a 100% incurable cancer, the goal of lymphoma treatment is to prolong the total survival time and minimize side effects during treatment. In the phase 3 clinical trial of PLS-D5000, the experimental group to which PLS-D5000 was applied after chemotherapy was compared with the control group treated only with the existing chemotherapy method to determine the total survival time and recurrence rate.
An official from Plumline Life Sciences said, “About 150,000 dog chemotherapy cases are counted annually in the US market alone, and more than $10,000 is paid for dog chemotherapy. It is possible, and it has a technological advantage that can induce high cellular immunogenicity, which is related to the survival rate of dogs with cancer.”
https://m-thebell-co-kr.translate.goog/m/newsview.asp?svccode=00&newskey=202203241006130400108585&_x_tr_sch=http&_x_tr_sl=auto&_x_tr_tl=en&_x_tr_hl=en
3/25 Researchers studied 141 people infected with the virus in the first half of 2020 who provided blood samples 12 months later. None of them had been vaccinated in the interim. Most individuals still had low levels of antibodies, and most of those younger than 60 still had some antibodies that could neutralize the virus, according to a report published on Wednesday in The Lancet Microbe. But in everyone - regardless of age or severity of the original infection, and including patients who had lost their neutralizing antibodies - responses by so-called memory B cells and memory T cells were still evident "and were not disrupted by new variants," the researchers said. These defenses do not prevent infection but they do help to prevent severe disease.
"Current SARS-CoV-2 vaccines are mainly focused on neutralizing antibodies," the researchers noted. "These data underline the importance of broad B-cell and T-cell immunity for future vaccine strategies targeting SARS-CoV-2."
https://www.reuters.com/business/healthcare-pharmaceuticals/some-immune-system-memory-persists-year-after-infection-covid-omicron-also-less-2022-03-25/
https://www.thelancet.com/action/showPdf?pii=S2666-5247(22)00036-2
We exceeded our goal to advance the development of the miRNA biomarker IVD platform, yielding 7.5% credit (which was 125% of the target weighting of 6% credit);
We exceeded our goal surrounding RRP-001 dosing, yielding 7.5% credit (which was 125% of the target weighting of 6% credit);
We successfully submitted a proposed amendment to the RRP Phase 3 trial design, yielding 2% credit;
We significantly exceeded our goal with respect to MERS dosing, yielding 4.5% credit (which was 150% of the target weighting of 3% credit;
We met our goal related to the Zika dMAb trial, yielding 4% credit
We partially met the goals surrounding the manufacturing of DNA plasmid, devices, and arrays, yielding 5% credit of the possible 8%;
To start P1 dMAbs for Prevention of COVID-19 May 2022
Estimated Study Start Date : May 2022
Estimated Study Completion Date : May 2023
This May exceed initial goal of 2H22.
March 25 (Reuters) - The U.S. health regulator said on Friday the current authorized dose of GlaxoSmithKline (GSK.L) and Vir Biotechnology's (VIR.O) antibody-based COVID-19 treatment is unlikely to be effective against the Omicron BA.2 variant.
The agency pulled its authorization for the therapy in much of the U.S. northeast where the subvariant is dominant.
It updated its emergency use authorization factsheet on sotrovimab and also updated its website to exclude the drug's use in geographic regions where infection is likely to have been caused by a non-susceptible SARS-CoV-2 variant.
The U.S. Centers for Disease Control and Prevention (CDC) has identified that the BA.2 variant is now circulating with a frequency exceeding 50% in Connecticut, Maine, Massachusetts, New Hampshire, Rhode Island, Vermont, New Jersey, New York, Puerto Rico, and the Virgin Islands.
As a result, the Office of the Assistant Secretary for Preparedness and Response said it would pause distribution of sotrovimab to these states.
GSK and Vir said on Friday they are preparing a package of data in support of a higher dose of the therapy for the BA.2 subvariant and will be sharing the data with regulatory authorities around the world for discussion.
The currently authorized dosage for sotrovimab is 500 mg. It is authorized for adults and children 12 years of age and older, and who are at high risk for progression to severe COVID-19.
3/25/22 “We believe this is an important step for dMAb program.
This has to do with announcement we had made in December 2020 regarding dMAbs to treat Covid19. We are working with many collaborators on this project as you know. We are hoping that this can lead to benefits not just for Covid but for our dMAbs program, in general.
Thank you
Investor Relations”
P1 dMAbs for Prevention of COVID-19
https://clinicaltrials.gov/ct2/show/NCT05293249?term=Dmabs&draw=2&rank=1
Recombinant monoclonal antibodies represents the largest segment of pharmaceutical markets today with more than $100B in sales.
In 2020, the Company received a $10.7M sub-grant through Wistar, which was amended in 2021 to $13.5M, for the preclinical development and translational studies of dMAbs as countermeasures for COVID-19, with funding through September 2022. The sub-grant also includes an option for an additional $6.0M in funding through September 2024, of which $3.3M has been exercised as of December 31, 2021.
Moderna stock falls 8% as SVB Leerink lowers price target; sees 55% downside
#MRNA has never managed to field a product where AEs (and pretty much the same set of AEs) did not produce more risk and harm than the pathogen they were targeted against. The company has been seeking progressively more deadly diseases to work with to change the risk equation and still couldn't field a finished drug or turn a profit since its inception, losing 100-200m annually until 2021.
Covid has been their only fielded product, period, and you know how that went - same sets of AEs.
The lipid nanoparticles are problematic. The adenovirus vector is problematic. These are the fundamental components of their product; changing the package contents is irrelevant when the container is what kills you.
https://stocktwits.com/Brooxsie/message/447121894
Though new orders from Japan and Colombia helped Moderna boost its expected revenue from Covid vaccines this year from $19 billion to $21 billion, the firm also shared phase 2 trial data for its flu vaccine candidate that showed only “similar” efficacy to standard flu shots, making it difficult to say whether the candidate is “necessarily better,” Jefferies analysts said Friday.
Other analysts were harsher on the data, with SVB Leerink’s Mani Foroohar calling the results a “nonstarter for the influenza market,” both commercially and clinically, and saying any further development of the candidate would be a “poor use” of Moderna’s resources.
Though several analysts praised Moderna’s efforts to develop vaccines against latent (also known as dormant) viruses—including cancer, multiple sclerosis and congenital deafness—a few acknowledged investors are still focused on the firm’s Covid offerings.
Morgan Stanley, which holds a price target of $170 for Moderna shares, pointed out it’s unlikely the UN’s Covax will exercise its option to purchase additional doses by an April 1 deadline, while lawmakers in the U.S. struggle to secure additional Covid funding.
Nearly 77% of Americans ages five and older have received at least one COVID-19 vaccine dose so far, according to the Centers for Disease Control & Prevention (CDC). The number is even higher -- 88% -- for adults ages 18 and older. But these doses were free to all Americans. If there had been even a nominal cost, the percentages would almost certainly be significantly lower.
Also, the costs of vaccines will increase in a private market. Bancel acknowledged on Thursday, "In an endemic setting, I believe Moderna's average price for the vaccine will be higher than it's been over the past two years." You can expect BioNTech (along with its partner, Pfizer) and Novavax to take a similar stance.
3/24/22 18-ppl P1, open-label, single center, dose escalation study to evaluate the safety and pharmacokinetic profile of mAb AZD5396 and mAb AZD8076 following delivery of optimized dMAb AZD5396 and dMAb AZD8076 with Hylenex® recombinant, administered by intramuscular injection (IM) followed immediately by electroporation (EP) using the CELLECTRA® 2000 with Side Port needle device, in a 2-dose regimen (Days 0 and 3) in healthy adults.
The hypothesis is that the administration of dMAb AZD5396 and dMAb AZD8076 will be safe and associated with expression of mAb AZD5396 and mAb AZD8076 in serum.
https://clinicaltrials.gov/ct2/show/NCT05293249?term=Dmabs&draw=2&rank=1
3/1/22, 10-K, pg 112: Ino, Wistar Institute, AstraZeneca, the University of Pennsylvania, and Indiana University received a $37.6M grant from DARPA to leverage AstraZeneca's CV monoclonal antibody and INOVIO's dMAb®. In 2020, the Company received a $10.7M sub-grant through Wistar, which was amended in 2021 to $13.5 million, for the preclinical development and translational studies of dMAbs as countermeasures for COVID-19, with funding through September 2022. The sub-grant also includes an option for an additional $6M in funding through September 2024, of which $3.3M has been exercised as of December 31, 2021.
Estimated Study Start Date :
May 2022
Estimated Study Completion Date :
May 2023
Sponsors and Collaborators
Pablo Tebas
The Wistar Institute
Inovio Pharmaceuticals
AstraZeneca
DoD
Recombinant monoclonal antibodies, which represent the largest segment of pharmaceutical markets today with more than $100 billion in sales, are designed to enhance the immune system's ability to regulate cell functions. However, the technology has some limitations, including long and costly laboratory development and large-scale production, limited duration of in vivo potency, and a pharmacokinetic profile that can result in toxicity. INOVIO's dMAb technology offers a disruptive and differentiated solution to the challenges and limitations associated with conventional recombinant monoclonal antibody-based treatments. The company can encode the DNA sequence for a specific monoclonal antibody in a DNA plasmid and deliver the plasmid directly into cells of the body using the company's proprietary smart device called CELLECTRA®. This specific DNA medicine serves as a genetic blueprint that instruct the patient's body to build its own highly specific antibodies in vivo.
World Vaccine Congress Washington 2022, WASHINGTON DC, 18 - 21 APRIL 2022
Apr 18 14:00
ANTIBODIES FOR INFECTIOUS DISEASES 2pm - 5pm
Keynotes
Mark Esser,Vice President, Early Vaccines and Immune Therapies, AstraZenecaUnited States
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 09:40
Inovio’s DNA COVID vaccine update
COVID & Beyond
Joseph Kim,Chief Executive Officer, Inovio Pharmaceuticals
Apr 21 11:30
GT-EPIC platform to target advanced hepatocellular cancer in a patient specific manner
Cancer and Immunotherapy
Niranjan Sardesai,President & Chief Executive Officer, Founder, Geneos Therapeutics
Apr 20 17:10
Panel: What are the risks to self-spreading viruses?
Veterinary
Stanley Plotkin,Emeritus Professor, University of Pennsylvania School Of Medicine
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
3Q21, 10-Q, Pg 31 In February 2021, Geneos completed a second closing of the Series A-1 preferred stock financing, in which the Company did not participate. Following this transaction, the Company held approximately 35% of the outstanding equity, on an as-converted to common stock basis.
The Company continues to exclusively license its SynCon® immunotherapy and CELLECTRA® technology platform to Geneos to be used in the field of personalized, neoantigen-based therapy for cancer. The license agreement provides for potential royalty payments to the Company in the event that Geneos commercializes any products using the licensed technology. The Company is not obligated to use any of its assets to fund the future operations of Geneos.
Revenue recognized from PLS consists of milestone, license and patent fees. For the three and nine months ended September 30, 2021, the Company recognized revenue from PLS of $95,000 and $220,000, respectively, and $83,000 and $1.3 million, for the three and nine months ended September 30, 2020, respectively. At September 30, 2021 and December 31, 2020, the Company had an accounts receivable balance of $139,000 and $67,000, respectively, related to PLS.
10-K, pg 29: During the year ended December 31, 2021, we derived 43% of our revenue from the procurement contract with the DoD that we entered into in June 2020 and 14% of our revenue from our collaborator Plumbline Life Sciences, a company of which we are an approximately 19% stockholder. During the year ended December 31, 2020, we derived 68% of our revenue from Advaccine and 18% our our revenue from Plumbline Life Sciences. During the year ended December 31, 2019, we derived 78% of our revenue from AstraZeneca. Our collaboration agreement with AstraZeneca was terminated in 2021.
3/23/22 Omicron's 'stealth' subvariant BA.2 could go 'wild' in Europe before going global, top epidemiologist says
While war rages in Ukraine, not much attention is being paid in Europe to rising Covid cases.
Germany has been reporting record high numbers of cases of between 250,000 to 300,000 new infections a day in the last week.
The rise in cases across the continent, from the U.K. and France to the Netherlands and Austria, is being driven by several factors
LONDON — While war rages in Ukraine, not much attention is being paid to surging Covid-19 cases across Europe that could soon start to filter out to the rest of the world.
The rise in cases across the continent, from the U.K. and France to Italy and Austria, is being driven by several factors: The lifting of most — if not all — Covid restrictions, waning immunity from vaccines and booster shots, and the spread of the more transmissible omicron subvariant, BA.2.
“We all hoped and expected a different turn now at the beginning of spring,” Ralf Reintjes, professor of epidemiology at the Hamburg University of Applied Sciences, told CNBC this week.
“But the situation in Europe is a bit bumpy at the moment, and in Germany ... the [case] numbers are at a very, very high level, and they’re still increasing and have been increasing for quite some time.”
Germany is seeing a surge in cases and has reported daily tallies of new infections of between 200,000 to 300,000 a day in the last week.
Reintjes said that the combination “of everyone thinking and expecting somehow that the pandemic is over now” and the relaxation of what he saw as protective Covid measures gives the BA.2 subvariant “a really good chance to spread extremely wild in many parts of Europe.”
“It’s difficult to predict but personally I think it’s very likely that this is going to continue its tour around the globe as well,” he added. “That’s what viruses in a pandemic usually do.”
“There are also quite a few reports that people who have got an omicron infection, or BA.1 variant, then a few weeks later got BA.2 infection,” he noted, adding that there is a good chance that this new variant will spread and act like “some sort of new wave of a new pandemic like seasonal flu.”
Public health officials and scientists are closely monitoring BA.2, a subvariant of the already highly transmissible omicron variant, as it is accounting for a growing number of new cases in Europe.
To a somewhat lesser extent it is also accounting for a growing number of infections in the U.S. and Asia.
The subvariant is estimated to be 1½ times more transmissible than omicron and is likely to usurp it as the globally dominant variant.
Initial data has shown that BA.2 is a little more likely to cause infections in household contacts when compared with BA.1. It’s not believed currently that the BA.2 variant causes more severe illness or carries an increased the risk of being hospitalized, however further research is needed to confirm this, according to a U.K. parliamentary report published earlier in March.
‘Stealth’ variant
BA.2 has been described as a “stealth” variant because it has genetic mutations that could make it harder to distinguish from the older delta variant using PCR tests, compared with its original omicron parent, BA.1.
The new subvariant is the latest in a long line to emerge since the pandemic began in China in late 2019. The omicron variant — the most transmissible strain so far — overtook the delta variant, which itself supplanted the alpha variant — and even this was not the original strain of the virus.
The World Health Organization has said it is monitoring BA.2 closely, which it said had now been detected in 106 countries, and has also noted a rise in global cases after a recent lull.
In its latest weekly update published Tuesday, the WHO said that after a consistent decrease since the end of January, the number of new weekly cases rose for a second consecutive week last week, with a 7% increase in the number of infections reported, compared to the previous week.
The WHO also noted that while omicron has a number of sublineages, BA.2 has become the predominant variant in the last 30 days, with 85.96% of the virus sequences submitted to GISAID, the public virus tracking database, being the BA.2 variant.
The WHO noted that weekly data shows that the proportion of BA.2 cases, compared to other sublineages, has increased steadily since the end of 2021, with the subvariant becoming the dominant lineage by week seven of 2022.
“This trend is most pronounced in the South-East Asia Region, followed by the Eastern Mediterranean, African, Western Pacific and European Regions. BA.2 is currently dominant in the Region of the Americas,” the WHO said.
In the U.K., the latest available data from the Office of National Statistics, for the week ending March 13, showed that the BA.2 variant is now the most common variant in England, Wales, Northern Ireland and Scotland. In the week that was surveyed, 76.1% of all sequenced Covid-19 infections from the survey were compatible with the BA.2 variant, and 23.9% were compatible with the original omicron strain.
In the U.S., the Centers for Disease Control and Prevention says that BA.2 cases now account for 34.9% of all cases in the U.S. with the subvariant making up over half the number of cases reported in some northeastern states, but it has noted that the overall number of infections is still declining from the record highs seen in January.
US20220073614 - DNA MONOCLONAL ANTIBODIES TARGETING PD-1 FOR THE TREATMENT AND PREVENTION OF CANCER ? 2H22: Initiate COVID-19 dMAb trial
Application Date
13.01.2020
Publication Number
20220073614
Publication Date
10.03.2022
https://patentscope.wipo.int/search/en/detail.jsf?docId=US353221277&_cid=P12-L12RLK-64638-1
CANCER ANTIGEN
The compositions and methods of the invention can be used in combination with an antigen, or fragment or variant thereof.
Markers are known proteins that are present or upregulated vis-à-vis certain cancer cells. By methodology of generating antigens that represent such markers in a way to break tolerance to self, a cancer vaccine can be generated. Such cancer vaccines can include the checkpoint inhibitor(s) to enhance the immune response.
Aspects of the present invention include compositions for enhancing an immune response against an antigen in a subject in need thereof, comprising synthetic antibody in combination with a synthetic antigen capable of generating an immune response in the subject, or a biologically functional fragment or variant thereof.
In one embodiment, the synthetic antigen can be selected from the group including: hTERT, PSA, PSMA, STEAP, PSCA, and PAP, WT1, tyrosinase, NYES01, PRAME, and MAGE.
CANCER THERAPY
In one embodiment, the invention provides methods for preventing metastasis of malignant tumors or other cancerous cells as well as to reduce the rate of tumor growth. The methods comprise administering an effective amount of one or more of the compositions of the invention to a subject diagnosed with a malignant tumor or cancerous cells or to a subject having a tumor or cancerous cells.
The following are non-limiting examples of cancers that can be treated by the methods and compositions of the invention: Acute Lymphoblastic; Acute Myeloid Leukemia; Adrenocortical Carcinoma; Adrenocortical Carcinoma, Childhood; Appendix Cancer; Basal Cell Carcinoma; Bile Duct Cancer, Extrahepatic; Bladder Cancer; Bone Cancer; Osteosarcoma and Malignant Fibrous Histiocytoma; Brain Stem Glioma, Childhood; Brain Tumor, Adult; Brain Tumor, Brain Stem Glioma, Childhood; Brain Tumor, Central Nervous System Atypical Teratoid/Rhabdoid Tumor, Childhood; Central Nervous System Embryonal Tumors; Cerebellar Astrocytoma; Cerebral Astrocytotna/Malignant Glioma; Craniopharyngioma; Ependymoblastoma; Ependymoma; Medulloblastoma; Medulloepithelioma; Pineal Parenchymal Tumors of intermediate Differentiation; Supratentorial Primitive Neuroectodermal Tumors and Pineoblastoma; Visual Pathway and Hypothalamic Glioma; Brain and Spinal Cord Tumors; Breast Cancer; Bronchial Tumors; Burkitt Lymphoma; Carcinoid Tumor; Carcinoid Tumor, Gastrointestinal; Central Nervous System Atypical Teratoid/Rhabdoid Tumor; Central Nervous System Embryonal Tumors; Central Nervous System Lymphoma; Cerebellar Astrocytoma Cerebral Astrocytoma/Malignant Glioma, Childhood; Cervical Cancer; Chordoma, Childhood; Chronic Lymphocytic Leukemia; Chronic Myelogenous Leukemia; Chronic Myeloproliferative Disorders; Colon Cancer; Colorectal Cancer; Craniopharyngioma; Cutaneous T-Cell Lymphoma; Esophageal Cancer; Ewing Family of Tumors; Extragonadal Germ Cell Tumor; Extrahepatic Bile Duct Cancer; Eye Cancer, intraocular Melanoma; Eye Cancer, Retinoblastoma; Gallbladder Cancer; Gastric (Stomach) Cancer; Gastrointestinal Carcinoid Tumor; Gastrointestinal Stromal Tumor (GIST); Germ Cell Tumor, Extracranial; Germ Cell Tumor, Extragonadal; Germ Cell Tumor, Ovarian; Gestational Trophoblastic Tumor; Glioma; Glioma, Childhood Brain Stem; Glioma, Childhood Cerebral Astrocytoma; Glioma, Childhood Visual Pathway and Hypothalamic; Hairy Cell Leukemia; Head and Neck Cancer; Hepatocellular (Liver) Cancer; Histiocytosis, Langerhans Cell; Hodgkin Lymphoma; Hypopharyngeal Cancer; Hypothalamic and Visual Pathway Glioma; intraocular Melanoma; Islet Cell Tumors; Kidney (Renal Cell) Cancer; Langerhans Cell Histiocytosis; Laryngeal Cancer; Leukemia, Acute Lymphoblastic; Leukemia, Acute Myeloid; Leukemia, Chronic Lymphocytic; Leukemia, Chronic Myelogenous; Leukemia, Hairy Cell; Lip and Oral Cavity Cancer; Liver Cancer; Lung Cancer, Non-Small Cell; Lung Cancer, Small Cell; Lymphoma, AIDS-Related; Lymphoma, Burkitt; Lymphoma, Cutaneous T-Cell; Lymphoma, Hodgkin; Lymphoma, Non-Hodgkin; Lymphoma, Primary Central Nervous System; Macroglobulinemia, Waldenstrom; Malignant Fibrous Histiocvtoma of Bone and Osteosarcoma; Medulloblastoma; Melanoma; Melanoma, intraocular (Eye); Merkel Cell Carcinoma; Mesothelioma; Metastatic Squamous Neck Cancer with Occult Primary; Mouth Cancer; Multiple Endocrine Neoplasia Syndrome, (Childhood); Multiple Myeloma/Plasma Cell Neoplasm; Mycosis; Fungoides; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Diseases; Myelogenous Leukemia, Chronic; Myeloid Leukemia, Adult Acute; Myeloid Leukemia, Childhood Acute; Myeloma, Multiple; Myeloproliferative Disorders, Chronic; Nasal Cavity and Paranasal Sinus Cancer; Nasopharyngeal Cancer; Neuroblastoma; Non-Small Cell Lung Cancer; Oral Cancer; Oral Cavity Cancer; Oropharyngeal Cancer; Osteosarcoma and Malignant Fibrous Histiocytoma of Bone; Ovarian Cancer; Ovarian Epithelial Cancer; Ovarian Germ Cell Tumor; Ovarian Low Malignant Potential Tumor; Pancreatic Cancer; Pancreatic Cancer, Islet Cell Tumors; Papillomatosis; Parathyroid Cancer; Penile Cancer; Pharyngeal Cancer; Pheochromocytoma; Pineal Parenchymal Tumors of Intermediate Differentiation; Pineoblastoma and Supratentorial Primitive Neuroectodermal Tumors; Pituitary Tumor; Plasma Celt Neoplasm/Multiple Myeloma; Pleuropulmonary Blastoma; Primary Central Nervous System Lymphoma; Prostate Cancer; Rectal Cancer; Renal Cell (Kidney) Cancer; Renal Pelvis and Ureter, Transitional Cell Cancer; Respiratory Tract Carcinoma Involving the NUT Gene on Chromosome 15; Retinoblastoma; Rhabdomyosarcoma; Salivary Gland Cancer; Sarcoma, Ewing Family of Tumors; Sarcoma, Kaposi; Sarcoma, Soft Tissue; Sarcoma, Uterine; Sezary Syndrome; Skin Cancer (Nonmelanoma); Skin Cancer (Melanoma); Skin Carcinoma, Merkel Cell; Small Cell Lung Cancer; Small Intestine Cancer; Soft Tissue Sarcoma; Squamous Cell Carcinoma, Squamous Neck Cancer with Occult Primary, Metastatic; Stomach (Gastric) Cancer; Supratentorial Primitive Neuroectodermal Tumors; T-Cell Lymphoma, Cutaneous; Testicular Cancer; Throat Cancer; Thymoma and Thymic Carcinoma; Thyroid Cancer; Transitional Cell Cancer of the Renal Pelvis and Ureter; Trophoblastic Tumor, Gestational; Urethral Cancer; Uterine Cancer, Endometrial; Uterine Sarcoma; Vaginal Cancer; Vulvar Cancer; Waldenstrom Macroglobulinemia; and Wilms Tumor.
Example 1
Simplifying Checkpoint Blockade Delivery Using DNA-Encoded Antibodies
CTLA-4 blockade and PD-1 blockade have demonstrated synergy and non-redundancy in pre-clinical mouse models and in patients. Due to the non-redundancy in these immune checkpoint pathways, the combination therapy of nivolumab and ipilimumab resulted in improved efficacy, including overall survival and progression free survival compared to monotherapy, resulting in the FDA approval for this combination therapy for advanced melanoma in 2015.
DMAb delivery simplifies antibody therapies and combinations, including checkpoint blockade, and can make them available to a much larger population. Clinical development of DMAb for cancer treatment is warranted.
Modifications were made to the sequence of different anti-PD-1 antibodies (Pembrolizumab and Nivolumab) to optimize their expression while retaining their binding ability and functionality ( FIG. 1 and Table 1). Optimized DMAb plasmids encoding anti-PD-1 and anti-CTLA4 antibodies does not only simplify the administration and regime of checkpoint blockade therapy, turning 90-minute intravenous infusions administered every three weeks into a single intramuscular injection. DMAbs will also simplify combination therapy, allowing administration of anti-CTLA4 and anti-PD-1 combinations with a single intramuscular injection or combinations with other therapies as DNA vaccines.
2/23/22 Serum Institute CEO details the state of global COVID-19 vaccine distribution
Video Transcript
ANJALEE KHEMLANI: Joining me now, CEO of Serum Institute of India, Adar Poonawalla. Adar, thank you so much for joining me today.
https://finance.yahoo.com/video/serum-institute-ceo-details-state-231355016.html
ADAR POONAWALLA: It's a pleasure to be here with you.
ANJALEE KHEMLANI: I want to start off with, obviously, looking at where we are right now in the world. We know that two years into this pandemic, we find ourselves sort of in a situation of a tale of two worlds, right, where there is a very heavily vaccinated half of the world and an under-vaccinated half as well. We seem to be at a crossroads, with some experts like Bill Gates specifically saying recently that it's, quote, "too late" to reach the World Health Organization 70% vaccination goal for the world and saying that, quote, "demand does not exist for that."
ADAR POONAWALLA: Well, you know, it's a funny predicament we find ourselves in because if you just rewind about six months to a year ago, there was this huge global shortage of vaccines-- or let's put it this way, WHO-approved, good, quality effective vaccines in the world. So as we saw that shortage sort of dissipate because you had a lot of vaccine supply coming out of even India and other parts of the world to the poorer nations-- to answer your question on vaccine equity and all of that-- we find ourselves at a point where the hesitancy, combined with the ability for countries, certain nations, to absorb the vaccine in their programs and actually administer it, getting the jabs into everyone's arms, is a challenge.
So when you see both these factors playing out, you've got COVID fatigue going on in certain nations where people don't want to hear anything about vaccines and COVID. They've just had enough. And you know, I don't blame them. We've all gone through hell.
So you've got that being an issue for the second dose and even booster doses. You've got, as I said, certain nations who just don't have the infrastructure, the cold chain capacity, other factors that are preventing those vaccines, which are now available in abundance. For example, we've got $400 million doses of stock of vaccine. I mean, that would have been crazy if we had that, you know, six months ago and very useful.
But sadly, we could only make a billion and a half doses, which was, of course, a lot more than what we had promised. And that still wasn't enough in 2021. But now in 2022, we're you know, fortunately, in a very, very good place.
ANJALEE KHEMLANI: Yeah, I want to talk about that. I know by late December, you were putting out about 250 million doses a month. And you warned that you would have to production just based on the demand. Knowing that right now there is still demand in the world, and we've seen India restart on a booster campaign-- to your point, there is still some unmet need. Where is your monthly output right now for the AstraZeneca Oxford vaccine, as well as where you're starting now for Novavax?
ADAR POONAWALLA: So we've got millions of doses on Novavax stockpiled, and we're starting exports now to Europe and many other countries now that you know it's approved. I, in fact, stopped the AstraZeneca vaccine production in December, because I had a stock of $400 million doses in addition to the 1.5 billion that we delivered to 70 countries, along with, you know, India being the major country receiving the supply of that vaccine.
So I had to actually make an emotional decision to shut down or pause the production, which can restart with a month's notice. We've got those facilities ready. But there's no point making anymore because we've got, as I said, a very large stockpile available. And I do see in quarter two and quarter three, let me just add, the vaccine demand picking up.
So to what you mentioned, to Bill Gates' point, it's right what he says. But I think hopefully, you know, demand will build up a little bit as the certain nations that haven't been able to absorb the huge quantities of vaccines pouring in from the United States, from India, and other parts of the world-- so let's see how that goes.
ANJALEE KHEMLANI: Where do you see that demand coming from? Because, to your point, there is hesitancy in part because of the uneven supply, especially when you talk about African countries-- you faced several setbacks, one with the fire last January, as well as the export ban. So where do you see this demand coming from, then?
ADAR POONAWALLA: Yes. I mean, we weren't set back a lot with the fire because we had multiple facilities. The reason we couldn't export is because we had an export ban, or temporary pause because we had to take care of our nation first, which is what all the other countries were also doing. Remember in Europe and in the US, until their populations were vaccinated, you couldn't have vaccines going even between Europe and the UK. There was an issue with the AstraZeneca vaccine being allowed to go from Europe to the UK.
So it was a universal kind of issue where the politicians and leaders decided to take care of their nation first, which was their primary responsibility. And as soon as we could then export, we did export. So now, you know, it's a free for all. We can export to any country that we want. And as I said, as these countries and nations pick up-- like, take, for example, the African continent.
You still haven't crossed a 40%, 50% vaccination coverage rate. I imagine that will happen in the second or third quarter of this year, because vaccine supply is no longer a constraint. It's just getting the vaccine out to every part of the country. And all these countries have vast geographical challenges as well with cold chains and other things to get the product out to everyone.
ANJALEE KHEMLANI: Do you feel like you lost an opportunity when it comes to those months with the export ban in place? I know you've talked about having had lowered the price as well as the potential loss of greater profits than you could have. Do you feel like you miss an opportunity to really build up that capital to then reinvest, considering some of the US companies, Western companies really got a windfall from this pandemic?
ADAR POONAWALLA: Well, you know, I think a lot of the pharmaceutical companies, including Serum Institute, has got a windfall because of the volumes and the crisis that we were handling. And don't forget, we were providing this vaccine, and still are, at $3 a dose. So compared to all the other vaccines that were available, even the Chinese and Russian ones, forget the American vaccines, which were going at $20-- even the Chinese and Russians were selling at $10.
So you know, we've always ethically priced our vaccines to make them as affordable and accessible to the poorer nations. And yes, it was a blow to our reputation, which we're slowly clawing back because, you know, even the African continent is aware that we've always been there to support them for the last two, three decades, providing so many vaccines at affordable prices compared to what was available from Western pharmaceutical companies. And it's because, you know, our cost base has always been lower.
So we were able to provide these vaccines at a lower price. I think very soon you're going to see a lot of the Indian vaccines go to the African continent and restore the faith and original reputation that we enjoyed.
ANJALEE KHEMLANI: I want to talk about the vaccine specifically. I know you've done Oxford AstraZeneca, also Novavax, also looking at Sputnik. But there is definitely a push, especially in South Africa, to build up for mRNA hubs and the like. Do you see the opportunity there? And are you planning to invest in building out for mRNA, either for this pandemic or future ones?
ADAR POONAWALLA: Well, you know, as you know, this sort of thing is a very specialized activity. It'll take a lot of time. I don't know if we'll ever set up a facility on the African continent. Maybe Ghana and Rwanda are two countries that we're looking at-- maybe not South Africa-- maybe even South Africa, but you've got great companies in South Africa that can make vaccines as well.
I think as time goes on, we'll see our investment in messenger RNA first proving itself in India, and then maybe, you know, we expand in other countries. But don't forget, all the countries that took the messenger RNA vaccines have shown a decline in immunity. We've seen that across the board.
If you look at India and the level of cases and hospitalizations, which have predominantly taken 88% of India's vaccinated the Oxford-AstraZeneca vaccine, you've seen one-fifth of the hospitalizations and severity of disease even just with two doses. I mean, don't forget we've not boosted our population like some of the other nations have Germany, United States, so many other countries.
So I'm actually a big fan of the traditional technology and vaccines in terms of their ability to protect for the long-term and also reduce severity of disease. So I'm still not sold and convinced on messenger RNA, although I'm not ruling it out. We've made investments in that technology. And maybe in two years, we're looking at leveraging that platform to make some vaccines.
But at the moment, I'm still not convinced whether messenger RNA technologies are the best way to provide long-term effectiveness. In the short-term, they're very powerful. They're very safe and good. But, you know, we're just waiting to see that real world data come out.
ANJALEE KHEMLANI: You've also diversified throughout the pandemic. I know you've had a lot of things going on. But one of the things that you've done is made sure that you have the capacity to produce your own glass viles and syringes as well-- as well as COVID tests. So where do you see the long term play for this? Is this just for the pandemic and also for future pandemics? Or is there another way to leverage this new investment?
ADAR POONAWALLA: Yes. I mean, we bought up to close to 50% in the largest RT, PCR, and rapid antigen test manufacturers called My Labs, and similarly in Shot Guisha, which is the largest glass vile and ample manufacturer in India. So you know, post-pandemic-- and we all knew this would last for a year or two at best-- so post-pandemic, you know, these industries are always piggybacking on the health care systems and the advancements that we have in disease, and monitoring, and genomic sequencing to know what kind of viruses are going around and what kind of strains are circulating.
So I see a tremendous future for the testing part and diagnostics part. And you know, I backed these entrepreneurs who've got and developed various other tests for HPV, for STDs, for so many other things that we'll need beyond COVID. And also, don't forget anyone in the pharmaceutical industry, it's always great to backward integrate.
You know, if I can have more control on my supply chain, that's one thing we learned during this pandemic. And I don't imagine we're going to be in that kind of situation every few years. But it would be great to have some control and say on your own major critical raw materials that you use to fill, package, and manufacture your vaccines or pharmaceutical products. So it was with that in mind that we bought a stake in Shot Guisha as well.
ANJALEE KHEMLANI: Let's move on to you. You specifically have faced unprecedented scrutiny throughout this pandemic, both from being at home and abroad. There was just a lot of conversation about your specific moves. What have you learned from all of this in the past year or two? And what do you think you can apply moving forward?
ADAR POONAWALLA: Well, I mean, you know, it's been an incredible journey, as you rightly put. Every month, there was a new challenge and a new unexpected challenge. So I think whilst dealing with uncertainty the way I've had to personally deal with things, with a lot of public scrutiny as you rightly put, I think one thing we've all learned is don't make forward-looking statements, talk about things when they actually happen rather than talking about, you know-- even when you're pressed and you ask the question, how much do you think you're going to do, or what you're going to do, when are you going to do it-- I think one thing we've all learned is don't make forward-looking statements.
A lot of people talked about when they thought the pandemic would end or subside. I think they regretted their statements. So I think that's one lesson we've all learned, especially when faced with so much uncertainty. I certainly have.
I think the other thing that I learned was how to compartmentalize each issue. Because if I had to think about every night before I go to bed on everything that I have to get done in the next week or month, I would have had a nervous breakdown. So one sort of tool I used was to just focus on one issue at a time or separately, and not think about anything else, and just focus on the task at hand.
So you know, when you've got to act under a lot of pressure, and you have timelines, and you have public scrutiny-- and a lot of responsibility, and rightly so, because everyone needed this, and wanted to know, and depended on us, that we had taken this risk and we were going to be the largest players in supplying the vaccine, it was an incredible responsibility that I felt that I had to succeed and, at any cost, just perform in a timely manner.
And you know, that's what-- I think-- I hope I did my best. And you know, I don't have any regrets on that.
ANJALEE KHEMLANI: Well, speaking of forward-looking statements, what do you see as the outlook for 2022?
ADAR POONAWALLA: Well, I think it's very good, as we discussed. You know, I hope the markets also now recover. And generally, I think everyone is coming to the conclusion that as long as-- and here's the rider-- as long as this strain doesn't mutate to a worse, more severe version, Omicron and, you know, even the B-2 variant and these other variants that are circulating aren't causing a lot of hospitalizations and deaths-- partly because of, you know, the strains becoming weaker and partly, of course, because the vaccines are providing a long term t-cell immune response.
In fact, we've seen a lot of people who haven't had COVID at all, or at least they don't know they've had COVID. And that's partly, you know, because of the long-term t-cell immune response that they've built up over the years. And of course, with the vaccine, we've seen it's much, much better.
In fact, another point was that you know the long COVID that people are suffering from, I think you're half as likely or something like that, I read, was if you took the vaccine versus you getting COVID, and then recovering, and then having long COVID. So if you keep all those factors in mind, it's absolutely important and imperative to get vaccinated.
Having said that, you know, this strain is weakening. And I hope it continues to weaken. So I think the outlook is very good and positive. I think by the end of this year, provided, again, there is no major variant of concern that causes severe disease, I think we're out of it. And I think COVID shots will probably become something like a flu shot where you take an annual booster if you feel, you know, you're in a vulnerable category or you just want to protect yourself. So I imagine it becoming like that.
ANJALEE KHEMLANI: Certainly we'll all be keeping an eye on that. So we'll have to leave it there for now. But again, Adar Poonawalla, CEO of the Serum Institute of India, thank you so much again for joining us. And also a note of congratulations to your father for winning the Padma Bhushan Award.
ADAR POONAWALLA: Thank you so much. Thank you.
3/21/22 Sinovac’s low efficacy causes concern
Data indicating the Sinovac Biotech Covid-19 vaccine is less effective than an mRNA vaccine at preventing death in elderly people in Hong Kong is a red flag for mainland China, where infections are climbing and a vast swathe of the population is inoculated with the inactivated shot.
https://www.dailymaverick.co.za/article/2022-03-21-hong-kong-signals-policy-shift-south-africa-registers-566-new-cases/
Almost 3% of people aged 80 or older, who got two doses of the inactivated CoronaVac shot, died after getting infected, compared with 1.5% of those who were given the BioNTech SE vaccine, according to a preliminary analysis conducted by the Centre for Health Protection.
[This is why China will fast track heterologous 4800 and EUA]
Getting just one dose of either offered less protection, with 5.8% of those given CoronaVac and 3.4% of those given the mRNA shot subsequently dying.
Shanghai – China’s latest Covid hotspot
Shanghai reported a surge in Covid-19 infections after expanding its mass testing programme, sparking concern
the virus may be more widespread in the financial centre than previously thought.
The city saw a record 758 new cases on Sunday, including 734 asymptomatic patients, with the daily caseload doubling in two days, according to the National Health Commission.
The city last week ruled out imposing a broad lockdown, but officials said Monday that some areas will remain locked down for further testing.
Hong Kong eases Covid measures but spread continues
Hong Kong’s moves to ease some curbs were spurred by frustration in the banking community and wider population, which has endured more than two years of effectively closed borders and increasingly extreme quarantine measures, even though the virus is now spreading widely through the city.
While the travel easing had been foreshadowed by local media, Chief Executive Carrie Lam went a step further in laying out a plan to ease Hong Kong’s physical distancing rules in phases, starting from 21 April, as long as there is no rebound in infections.
No new cases in Hong Kong care homes
Hong Kong reported no new virus cases in residents at care homes, health officials said at a regular briefing on Monday.
The virus had spread rapidly through the facilities in recent weeks, and most fatalities during the current wave have been elderly people.
The city reported a total of 14,068 new infections, as well as 179 deaths.
REVEAL 2
Last Update Posted: January 11 => March 17, 2022 [Actual]
Primary Completion: July 2022 [Anticipated]
Study Completion: August 2022 [Anticipated]
Overall Status: Active, not recruiting
https://clinicaltrials.gov/ct2/history/NCT03721978?A=34&B=35&C=merged#StudyPageTop
P2a INO-5401 + INO-9012 in Combination With Atezolizumab in Locally Advanced Unresectable or Metastatic/Recurrent Urothelial Carcinoma
Primary Completion: December 30, 2021 => June 30, 2022 [Anticipated]
Study Completion: December 30, 2021 => June 30, 2022 [Anticipated]
Study Start: May 24, 2018
Last Update Posted: October 4, 2021 [Actual] => January 18, 2022 [Actual]
Overall Status: Active, not recruiting
https://clinicaltrials.gov/ct2/history/NCT03502785?A=26&B=27&C=merged#StudyPageTop
Primary Outcome Measures :
Number of Adverse Events [ Time Frame: From baseline up to 90 days after last dose of study medication (up to approximately 2 years and 3 months) ]
Antigen-Specific Cellular Immune Response [ Time Frame: At baseline, Weeks 3, 6, 9, 12 and every 12 weeks thereafter up to end of study (up to approximately 2 years) ]
Objective Response Rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by Investigator Review in Cohort A [ Time Frame: From Baseline to disease progression or death, whichever occurs first (up to approximately 2 years) ]
3/19/22 The COVID-19 situation in China is getting worse and worse.
According to the announcement by the National Health Commission of China on the 19th, for the first time since January 25 of last year, the number of deaths from COVID-19 occurred the day before. The National Health Commission announced on the previous day that there were 2,228 new cases of COVID-19 in China, with two deaths. With this, the cumulative number of confirmed cases in China rose to 128,462 and the cumulative number of deaths to 4,638. The National Health Commission said, "From 00:00 to 24:00 on the 18th, a total of 2228 new cases of COVID-19 were reported across China, including 31 provinces and Xinjiang. thing," he said. There were 2157 local cases of infection in China. Of these, 1,674 were from Jilin Province. In Jilin City alone, 941 cases were confirmed, 742 cases in Changchun City, 12 cases in Shiping City, and 6 cases in Yanbian Korean Autonomous Region. In Jilin Province, where the death toll has been reported for the first time in about 14 months, the COVID-19 situation appears to be quite serious. Jilin Province is currently under a travel ban that requires police permission to cross the state border. In addition, following Changchun City, Jilin City has also imposed a de facto city blockade and is conducting a complete nucleic acid (PCR) test.
“The infection situation in Changchun and Jilin, which accounts for 98% of Jilin’s infections, is still grim and complicated,” said Zhang Li, vice director of the Jilin Provincial Health Commission. picked
On the other hand, as of the previous day, the number of new confirmed cases by region in China was 199 in Fujian, the second highest after Jilin. Liaoning (69), Guangdong (47), Shandong (42), Tianjin (28), Gansu (22), Heilongjiang (20), Zhejiang (11), Shaanxi (11) ), Shanghai (8 cases), Hunan (6 cases), Yunnan (5 cases), Hebei (4 cases), Jiangsu (3 cases), Chongqing (3 cases), Guangxi (2 cases), Beijing Poetry (1 case) followed.
https://n-news-naver-com.translate.goog/article/008/0004721804?ntype=RANKING&_x_tr_sl=auto&_x_tr_tl=en&_x_tr_hl=en
3/18 Murky case for fourth doses now with FDA as protection wanes, BA.2 looms
https://arstechnica.com/science/2022/03/murky-case-for-fourth-doses-now-with-fda-as-protection-wanes-ba-2-looms/
Vaccine-makers Moderna and Pfizer have now both submitted requests for the US Food and Drug Administration to authorize fourth doses—second boosters—of their COVID-19 vaccines.
Pfizer, along with vaccine partner BioNTech, announced Tuesday that they had asked the FDA to authorize fourth doses for adults age 65 and above. The move followed days of Pfizer CEO Albert Bourla saying in press interviews that a fourth shot is "necessary" for everyone.
Late Thursday, Moderna announced that it, too, had asked the FDA to authorize fourth doses—for all adults. Moderna addressed the broader request in its announcement, saying it’s intended to "provide flexibility" for the FDA and the Centers for Disease Control and Prevention to decide for themselves who should get a fourth dose—whether it's specific age groups and/or groups with higher risks of disease.
The outlook for the submissions is murky. On one hand, real-world data indicates that protection from three doses is waning against omicron, particularly against infection. And although cases in the US are in decline for now, a yet-more-transmissible version of omicron—BA.2—continues to increase in prevalence. It's now estimated to account for 23 percent of cases in the US, furthering its steady progress in usurping the initial omicron variant, BA.1. The rise of BA.2, coupled with widespread relaxation of mitigation efforts, such as mask wearing and distancing, have many experts anticipating another rise in cases, as is currently happening in many countries in Europe. Already, SARS-CoV-2 levels in US wastewater are rising, signaling an early warning of increasing transmission. Together, this all makes an argument for use of a fourth dose now, at least in vulnerable populations.
But, on the other hand, it's unclear how much a fourth dose would help to prevent infections and how long such gains would last. Though vaccine effectiveness does appear to be waning across the board, protection from hospitalization and death remains strong. (Effectiveness against hospitalization four months after a third dose fell from 91 percent to 78 percent, CDC data found recently.) And much of the data on the effectiveness of fourth doses comes from Israel, where fourth boosters have been offered to several groups—including people age 60 and above, as well as health workers and people at high risk of exposure or disease—but only for a short period of time so far.
Israeli data
In one study, carried out with the help of the Israeli Ministry of Health, Israeli researchers analyzed health records of more than 1.1 million people age 60 and over who were eligible for a fourth dose amid the omicron wave. People with a fourth dose were two times less likely to be infected and around four times less likely to have severe COVID-19 compared with people who had only three shots, the analysis found. However, fourth doses were only recently offered, and the study period was short. The researchers weren't able to look at effectiveness past the first 23 days after a fourth dose. The study was posted online on a pre-print server and has not yet been peer-reviewed.
In another study published Wednesday in The New England Journal of Medicine, fourth doses seemed less useful against omicron. Researchers examined data on 1,050 Israeli health care workers who were eligible for fourth shots. Of those, 154 received a fourth dose of the Pfizer vaccine and 120 received a fourth dose of the Moderna vaccine. Overall, the fourth doses appeared safe and bolstered waning antibody levels compared with those in matched controls. However, effectiveness against infection was modest at best. While 25 percent of health workers in the control group were infected, so were 18 percent of people who got a fourth dose of the Pfizer vaccine and 21 percent of people who got a fourth dose of the Moderna vaccine.
The researchers estimated that the efficacy against any infection (asymptomatic and symptomatic) was 30 percent for the fourth Pfizer dose, and 11 percent for Moderna. But, with such a small study, none of those estimates reached statistical significance. Protection against just symptomatic infections appeared a little better: 43 percent for Pfizer and 31 percent for Moderna. But, again, with such a small study, the confidence intervals on those estimates were large. Still, the efficacy against symptomatic infection was, at best, 65 percent, the study authors highlight. "Thus, a fourth vaccination of healthy young health care workers may have only marginal benefits," the authors concluded. "Older and vulnerable populations were not assessed."
Data and debate
The murky data and the new submissions to the FDA are expected to once again spotlight a continued debate among public health and infectious disease experts: what is the exact goal of vaccination and boosting? Some, who have been more hesitant to recommend boosters during the pandemic, suggest that the primary goal is to prevent severe disease and death. That makes repeated boosters less necessary given the diminishing and short-lived benefits. Others, however, have argued that vaccines should also be used to smother transmission and infection, which would support widespread and repeated boosting.
For their parts, executives for Moderna and Pfizer have repeatedly suggested that fourth doses will eventually be needed for everyone and, in fact, the world is headed toward annual COVID-19 vaccines, much like seasonal flu shots.
It's still unclear how the FDA will fall in the debate and how it will review the current applications. However, FDA officials have said publicly that they are open to considering widespread use of fourth doses. In an interview with The New York Times in February, FDA's top vaccine regulator, Peter Marks, told the paper: “Barring any surprises from new variants, maybe the best thing is to think about our booster strategy in conjunction with the influenza vaccine next fall, and get as many people as possible boosted then.”
Hong Kong has registered the most deaths per million people globally in recent weeks – more than 24 times that in Singapore - due to a large proportion of unvaccinated elderly as Omicron ripped through care homes last month.
Currently only 56% of those over 80 have been vaccinated.
With infections spilling over on to the mainland and local cases hovering around 30,000 per day among a population of just 7.4 million, there needs to be a clear exit strategy, in line with learning to live with the virus, like other major cities, rather than trying to eradicate it, health experts say.
About half of the city's residents have likely already been infected, according to a study from the University of Hong Kong this week.
Increasing vaccinations to over 90% from about 80% currently is key, while protecting the most vulnerable, like those in nursing homes.
https://www.reuters.com/world/asia-pacific/clear-roadmap-needed-hong-kongs-revival-covid-sweeps-through-city-experts-2022-03-17/
3/19/22 Lancet: The primary objective of the Sisonke study was to assess the effectiveness of the single-dose Ad26.COV2.S vaccine to prevent COVID-19-related admission to hospital (hereafter referred to as hospitalisation), hospitalisation requiring critical care unit (CCU) or intensive care unit (ICU) admission, and death in health-care workers. Additionally, with a large proportion of the population living with HIV in South Africa, in post-hoc analyses, we were able to assess vaccine effectiveness among health-care workers living with HIV.
During the course of the study, the beta (B.1.351) and then the delta (B.1.617.2) SARS-CoV-2 variants of concerns were dominant, and vaccine effectiveness remained consistent (for scheme A plus B vaccine effectiveness against COVID-19-related hospital admission during beta wave was 62% [95% CI 42–76] and during delta wave was 67% [62–71], and vaccine effectiveness against COVID-19-related death during beta wave was 86% [57–100] and during delta wave was 82% [74–89]).
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(22)00007-1/fulltext
3/18/22 On plastic, the original Wuhan strain survived for about 56 hours. Most of the other variants tested, including Alpha, Beta, Delta and Omicron, survived more than three times as long. Omicron could still be detected 193 hours -- eight days -- after it was applied.
On skin, the Wuhan strain could be detected after eight hours. Other variants lasted more than twice that long, and Omicron could still be detected after 21 hours.
For the second study, researchers in Hong Kong spread samples of the original strain of the SARS-CoV-2 virus and the Omicron variant on squares of stainless steel, plastic, glass and paper. The original virus could be detected for only about two days on stainless steel and plastic, and for about four days on glass, but the Omicron variant could still be detected for about seven days on those surfaces. It survived longer on tissue and printer paper, too.
https://amp.cnn.com/cnn/2022/03/18/health/omicron-surfaces-studies/index.html
DNA Vaccine Therapy, INO-8000, INO-9012, EP in Treating Patients With Chronic Hepatitis C Virus Infection
Last Update Submitted that
Met QC Criteria: August 12, 2021 => March 17, 2022
https://clinicaltrials.gov/ct2/history/NCT02772003?A=24&B=25&C=merged#StudyPageTop
Sponsor:
National Cancer Institute (NCI)
Collaborator:
Inovio Pharmaceuticals
P30CA015083 ( U.S. NIH Grant/Contract )
https://reporter.nih.gov/search/yZ8pzDooUk-SQPkyNbxTZQ/projects
Ino to test 100-dma of $5.11, then 200-dma of $6.66. Advaccine finished recruiting 267-ppl for Heterologous Booster 4800 after Sinovac on 1/27/22 before Lunar NewYear 2/1/22. China normally shuts down 2 weeks for celebration. So, Advaccine wasted no time. They are motivated to expedite the trials for IPO to get high valuation to fund global commercialization. Expect Interim Readout April 2022 for 2,4,6,8 wks After dosing. Updated: 3/9/22
Recruiting time: From2021-12-22 To 2022-01-27
http://www.chictr.org.cn/showproj.aspx?proj=131321&fbclid=IwAR1AVdMvFu74Nx8-pOSgRo4VjZMy7l0knDclViZlyOK_rPbfPJwTi2OfN64
https://mb.com.ph/2022/03/06/7083-participants-of-who-solidarity-trials-get-first-dose-of-covid-19-jabs/
3/6/22 Expect STV Interim Readout April 2022. “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,” he noted.
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
3/18/22 COVID vaccination rate for people aged over 80 in China 'relatively low' -official
An elderly woman receives a dose of Sinovac Biotech's CoronaVac COVID-19 vaccine, following the coronavirus disease (COVID-19) outbreak, at a community vaccination centre, in Hong Kong, China, February 25, 2022. REUTERS/Tyrone Siu
BEIJING, March 18 (Reuters) - Only 19.7% of people aged over 80 in China have received a COVID-19 vaccine booster, while 50.7% of that age group have completed their primary vaccinations, a health official said on Friday.
"The percentage is still relatively low," Zeng Yixin, deputy director of the National Health Commission, told a news briefing.
Hong Kong reports 20,082 new COVID cases as city promised fewer restrictions
HONG KONG, March 18 (Reuters) - Hong Kong reported about 20,000 new coronavirus cases on Friday as health experts called for a clear way out of a "zero COVID" policy that has left the city isolated.
Densely populated Hong Kong has registered the most deaths per million people globally in recent weeks.
But restrictions, including a ban on flights from nine countries such as Britain and the United States, quarantine of up to 14 days for residents returning to Hong Kong, and the closure of schools, gyms, beaches and other venues, have frustrated many.
Hong Kong leader Carrie Lam said on Thursday she would provide an update on restrictions around March 20-21 rather than wait for them to expire on April 20. She acknowledged financial institutions were "losing patience" with COVID-19 policies.
On Friday, health authorities reported 20,082 COVID-19 cases, and 206 deaths. Daily cases have been hovering around 20,000-30,000 in recent days, although some experts say the real figure is significantly higher as many people test positive at home and do not report their result to the government.
There have so far been more than 1 million confirmed cases, and more than 5,000 deaths. But about half of the city's 7.4 million residents have likely been infected, a study from the University of Hong Kong estimated this week.
Many of the recent deaths are due to a large proportion of elderly people being caught unvaccinated after living in a relatively virus-free city for two years before the Omicron variant emerged.
With future outbreaks seen as inevitable, Hong Kong must make plans to eventually live with the virus, rather than insisting on eradicating all outbreaks, some epidemiologists say. read more
Mainland China, which has similar COVID policies, is also battling its worst outbreak since the virus first emerged in Wuhan in 2020. It reported 2,388 new local cases with confirmed symptoms on Thursday, almost double the count a day earlier. read more
President Xi Jinping signalled on Thursday that the "dynamic clearance" policy to contain the outbreak would not be ditched.
https://www.reuters.com/business/healthcare-pharmaceuticals/hong-kong-reports-20082-new-covid-cases-friday-2022-03-18/
3/15/22 JK “We have CELLECTRA 2000 that we are using for our clinical trials. We have extensive inventory to execute all of our trials, including COVID-19. We have CELLECTRA 5PSP that is currently being used in REVEAL1 and REVEAL2.
We have also used them in some of our Vulvar trial as well in P2. And we have plenty of inventory. We are actually gearing up commercial inventory, studying that as we prepare to wrap up REVEAL2 and potentially have the package in preparation for our feature commercialization.
And, of course, we are gearing up our CELLECTRA 3PSP both for regulatory approvals, but also for our potential emergency use. Once our INNOVATE and SOLIDARITY trials, once we can demonstrate efficacy and safety, of course, our endgame is to apply for emergency approval and then the full approval.
So, we have been solving the scaling up of device manufacturing. It’s one of those platform things. It does slow us down of our clinical device from going from P1, P2, P3 for COVID vaccine. But we have solved for these issues. And the beauty of this platform is that once you solve for them, you don’t have to deal with the same issues again. So, our inventories are very strong.“
("anti-vector responses" from multiple mRNA jabs)-“Our strategy of heterologous boost is there's a lot of science supporting that when you mix and match various vaccines, some of these parts are better than just homologous boosting or just sticking with Pfizer or Moderna or J&J. And some of the vaccines cannot be boosted because of the – like the viral vectors, adenovirus vector vaccines are going to have a trouble boosting because of the anti-vector responses you generate. Because of the formulations, some people may start to have more severe reactions to additional shots of boosters and such.
This is where I think DNA vaccines like INO-4800 will come to play an important role in this ever-boosting environment of COVID pandemic and subsequently endemic. Our vaccines have been shown to be able to be readministered without any anti-vector responses.”
”We have four separate Phase III trials going for our lead products, INO-4800 And VGX-3100, two Phase IIIs each. We have about 350 people.
In 2022, you could see Inovio bringing a third Phase III program. We're currently finishing a Phase I/II trial for our orphan drug indication against recurrent respiratory papillomatosis in INO-3107. We received the orphan designation in 2020. We look forward to having that data in 2022 from this Phase I/II trial, safety, immunogenicity and efficacy, and we're looking to push that into a Phase III trial before the year-end this year. So, we really have a lot going on. So, I think 2022 will be a very eventful year for Inovio.”