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3/8-9 2ND ANNUAL EUROPEAN HEALTHTECH CEO FORUM: Kate B., QIAGEN, TMO, HCW
12:10 CET 3/9/21 Overview of Vaccine Development & Roll Out Panel
Co-Chaired by:
Thomas Shrader, Managing Director & Healthcare Analyst, BTIG, LLC
Timothy Herpin, VP, BD, Infectious Diseases & Vaccines, Johnson & Johnson Innovation | Janssen Business Development
Panelists:
Andreas Neubert, Chief Scientific Officer, IDT Biologika GmbH
Johan Van Hoof, Global Therapeutic Area Head of ID & Vaccines & Managing Director, Janssen Vaccines & Prevention B.V.
Kate Broderick, Senior Vice President, Preclinical R&D, INOVIO Pharmaceuticals, Inc.
Nicholas Jackson, Head of Programmes & Innovation Technology for Vaccine R&D, Coalition for Epidemic Preparedness Innovations (CEPI)
13:30 Advanced Therapeutics Panel
Co-Chaired by:
Max Herrmann, Managing Director, Stifel Financial Corp.
Rao Movva, Novartis Distinguished Scientist & Independent Pharma & Biotech Advisor
Panelists:
Daniel Vitt, President & CEO, Immunic Therapeutics
Gilead Raday, COO, RedHill Biopharma Ltd.
Peter Llewellyn-Davies, CEO & CFO, APEIRON Biologics AG
Raghuram Selvaraju, Chairman of the Board of Relief Therapeutics Holding AG & Managing Director, H.C. Wainwright & Co., LLC Richard Marsden, CEO, Synairgen Research Ltd.
15:30 Diagnostics: New Technologies Panel
Chaired by:
Rainer Metzger, Head of Integrated Clinical Services, Medicover AB
Panelists:
Alexandra Vallon-Eberhard, Sr. Director Global BD - Diagnostics Biomarkers & Digital Healthcare Solutions, F. Hoffmann-La Roche Ltd. Christoph Pedain, Head of Point of Care Diagnostics, Siemens Healthineers AG
Jim Harper, Co-Founder & COO, Sonde Health
Martin Potgeter, Vice President, Corporate Business Development, QIAGEN GmbH
15:00 Keynote: “Blitzscaling” Atoms vs Bytes: Key Learnings from Pandemic Response
by Mark Stevenson, Executive Vice President & Chief Operating Officer, Thermo Fisher Scientific
https://www.sachsforum.com/uploads/5/1/9/6/51964431/ehtf_draft_agenda.pdf
Qiagen, Inovio expand collaboration to develop NGS companion diagnostic 05:26 QGEN, INO Qiagen (QGEN) and Inovio (INO) announced an extension of their partnership with a new master collaboration agreement to develop liquid biopsy-based companion diagnostic products based on next-generation sequencing, or NGS, technology to complement Inovio's therapies. The initial project in this expanded collaboration focuses on the co-development of a diagnostic test that identifies women who are most likely to benefit from clinical use of VGX-3100, Inovio's immunotherapy to treat advanced cervical dysplasia associated with the human papillomavirus, or HPV. Qiagen's bioinformatic expertise will further increase the predictive power of Inovio's preliminary biomarker signature - and the assay will now be developed for use on the Illumina NextSeq 550Dx platform, the first development based on a partnership Qiagen and Illumina signed in October 2019. VGX-3100 is INOVIO's late-stage DNA immunotherapy candidate. It is currently in two Phase 3 trials, with the potential to become the first non-surgical treatment for advanced pre-cancerous cervical lesions associated with the virus. Qiagen and Inovio in 2019 announced a collaboration to develop a companion diagnostic to guide clinical decision-making for the use of Inovio's DNA-based immunotherapy to treat cervical dysplasia caused by HPV. The new master collaboration agreement covers the development of companion diagnostics for Inovio's HPV therapies for a range of sample types and technologies such as PCR and NGS. Qiagen pioneered HPV testing with the gold-standard digene Hybrid Capture 2 High-Risk HPV DNA Test, which became a driving force in HPV screening as a standard of care in cervical cancer prevention.
http://ir.inovio.com/news-releases/news-releases-details/2021/INOVIO-and-QIAGEN-expand-collaboration-to-develop-next-generation-sequencing-NGS-companion-diagnostic-for-INOVIOs-VGX-3100-for-advanced-cervical-dysplasia/default.aspx
Regeneron and Sanofi Collab Libtayo Picks Up Third FDA Drug Approval
Published: Feb 23, 2021
The longtime partnership between Regeneron and Sanofi continues to yield fruit. On Monday, the companies announced their checkpoint inhibitor Libtayo (cemiplimab-rwlc) won Food and Drug Administration (FDA) approval for lung cancer.
Libtayo was approved for the first-line treatment of patients with advanced non-small cell lung cancer (NSCLC) whose tumors have high PD-L1 expression. Under the criteria set forth by the regulatory agency, NSCLC patients who receive Libtayo must either have metastatic or locally advanced tumors that are not candidates for surgical resection or definitive chemoradiation, and the tumors must not have EGFR, ALK or ROS1 aberrations, Regeneron said in its announcement.
Lung cancer is the leading cause of cancer death worldwide. In 2020, an estimated 2.2 million and 225,000 new cases were diagnosed worldwide and in the U.S, respectively. Approximately 84% of all lung cancers are NSCLC, with 75% of these cases diagnosed in advanced stages and an estimated 25% to 30% of cases expected to test positive for PD-L1 in 50% of tumor cells.
The approval was based on data from the Phase III clinical trial, called EMPOWER-Lung 1 that demonstrated the drug extended overall survival compared to chemotherapy in study patients. In this patient group, Libtayo reduced the risk of death by 43% compared to chemotherapy. This was achieved with a greater than 70% crossover rate to Libtayo following disease progression on chemotherapy, the companies said.
The primary endpoints were OS and PFS, and secondary endpoints included overall response rate, duration of response and quality of life. The trial included 710 patients who had either previously untreated metastatic NSCLC (Stage IV) or locally advanced NSCLC (Stage IIIB/C) who were not candidates for surgical resection or definitive chemoradiation or who had progressed after treatment with definitive chemoradiation.
Enrolled patients included those with disease characteristics frequently underrepresented in pivotal advanced NSCLC trials, the companies said. Among them, 12% had pre-treated and clinically stable brain metastases and 16% had locally advanced NSCLC that was not a candidate for definitive chemoradiation, Regeneron and Sanofi noted.
Monday’s approval marks the third for Libtayo, a fully-human monoclonal antibody targeting the immune checkpoint receptor PD-1 on T-cells. Libtayo was first approved as a treatment for adults with metastatic cutaneous squamous cell carcinoma (CSCC) or locally advanced CSCC who are not candidates for curative surgery or curative radiation.
Earlier this month, Libtayo won FDA approval as the first immunotherapy indicated for patients with advanced basal cell carcinoma (BCC) previously treated with a hedgehog pathway inhibitor (HHI) or for whom an HHI is not appropriate.
“With this third approval for Libtayo, we are proud to deliver on our ambition to bring our PD-1 inhibitor to patients in need with difficult-to-treat cancers, such as advanced non-small cell lung cancer," Peter C. Adamson, Global Development Head of Oncology and Pediatric Innovation at Sanofi said in a statement. “As the leading cause of cancer deaths globally, the need for additional therapeutic options in advanced NSCLC is clear. Libtayo allows physicians to further optimize treatment of these patients whose tumors have high expression of PD-L1.”
https://www.biospace.com/article/regeneron-s-and-sanofi-s-libtayo-picks-up-third-fda-approval-in-nsclc/
April 2021 Monetized-able P3 REVEAL1 (Evaluation of VGX-3100 and Electroporation for the Treatment of Cervical HSIL) readout for:
Cervical Dysplasia
Cervical High Grade Squamous Intraepithelial Lesion
HSIL
Could trigger a large collaboration and licensing agreement. It’s about time Ino monetizes its flagship.
Actual Study Start Date :
June 28, 2017
Actual Primary Completion Date :
July 8, 2020
Estimated Study Completion Date :
April 2021
Last Update Posted: February 3, 2021 [Actual]
Actual Enrollment :
201 participants
Brief Summary:
HPV-301 is a prospective, randomized, double-blind, placebo controlled Phase 3 study to determine the efficacy, safety, and tolerability of VGX-3100 administered by intramuscular (IM) injection followed by electroporation (EP) delivered with CELLECTRA™ 5PSP in adult women with histologically confirmed cervical high grade squamous intraepithelial lesion (HSIL) (cervical intraepithelial neoplasia grade 2 [CIN2] or grade 3 [CIN3]) associated with human papillomavirus (HPV) 16 and/or HPV-18.
P3 REVEAL2 Last Update Posted: February 4, 2021 [Actual] shows 3 Brazil, 2 US sites finished enrollment, 2 US sites completed the study. 1 S. Africa site was added.
Estimated Enrollment :
198 participants
Actual Study Start Date :
April 9, 2019
Estimated Primary Completion Date :
April 30, 2021
Estimated Study Completion Date :
May 30, 2021
Augusta University
[Active, not recruiting]
Augusta, Georgia, United States, 30912
New Jersey Medical School
[Active, not recruiting]
Newark, New Jersey, United States, 07103
Unified Women's Clinical Research - Hagerstown
[Completed]
Hagerstown, Maryland, United States, 21740
Unified Women's Clinical Research - Morehead City
[Completed]
Morehead City, North Carolina, United States, 28557
Associação Obras Sociais Irmã Dulce Hospital Santo Antônio
[Active, not recruiting]
Salvador, Bahia, Brazil, 40420-000
Hospital das Clinicas de Goiânia
[Active, not recruiting]
Goiânia, Goiás, Brazil, 74605-050
Hospital Erasto Gaertner
[Active, not recruiting]
Curitiba, Paraná, Brazil, 80530-010
https://clinicaltrials.gov/ct2/history/NCT03721978?A=26&B=27&C=merged#StudyPageTop
Libtayo used in INO-5401 GBM scores second OK in two weeks, this time for front-line NSCLC. Can it take on Keytruda?
February 22, 2021 04:57 PM EST
Coming up behind the other major PD-1 players, Regeneron sought to create its own market for Libtayo by going into indications where others have yet to venture — a strategy CSO George Yancopoulos likes to boast about. Now, the drug can directly compete against the heavyweights with its third approval.
The FDA gave Libtayo the green light as a monotherapy for advanced non-small cell lung cancer in the first-line setting, the same indication that made Merck’s Keytruda one of the most successful franchises in pharma. But it hasn’t been easy going for every drug: Bristol Myers Squibb’s Opdivo suffered one of its worst flops in NSCLC almost four and a half years ago.
Monday’s approval comes less than two weeks after the drug scored a separate OK in both forms of advanced basal cell carcinoma. That regulatory milestone essentially cemented Regeneron’s position in dermato-oncology, per analysts, coming more than two years after its first approval in metastatic cutaneous squamous cell carcinoma.
In this new indication, patients taking Libtayo must have PD-L1 expression of at least 50%, have metastatic or locally advanced tumors that can’t be removed by surgery and must not have EGFR, ALK or ROS1 aberrations.
Libtayo’s entrance into the NSCLC market comes off the basis of Phase III data they revealed in full last September at ESMO, as it will now seek to make up for lost time. Across 710 patients in the 1-to-1 randomized, double-blinded trial, those who received Libtayo lived for a median of 22 months, compared to 14 months for those on chemotherapy.
That translated to a 32% reduction in risk of death in all patients who expressed PD-L1, as well as a 43% reduction for patients confirmed to express PD-L1 above 50%.
“Notably, Libtayo was approved based on a pivotal trial where most chemotherapy patients crossed over to Libtayo following disease progression,” trial steering committee member Naiyer Rizvi said in a statement.
Though cross-trial comparisons are rough, the numbers are in line or higher than what Merck reported for its long-term study on Keytruda as a monotherapy in NSCLC. Merck reported that the reduction in risk of death was 32% for those who had at least 50% PD-L1 expression and 19% for those with PD-L1 expression above 1%.
Regeneron cancer chief Israel Lowy told Endpoints News back in September that the Libtayo trial was also closer to a real-life setting than Merck’s, given the latter’s stricter enrollment criteria.
But it remains to be seen how quickly the uptake will be, simply due to Keytruda’s dominance of the NSCLC market. Many patients also don’t receive a checkpoint inhibitor on its own, but rather a combination of checkpoint and chemotherapy. Lowy noted at the time that some physicians may choose monotherapies in cases with high expression for those who don’t want to, or can’t, undergo the rigors of chemo.
In a note out to investors early Tuesday morning, SVB Leerink analyst Geoffrey Porges wrote that he thinks Libtayo could take up about 5% of the overall $8 billion PD-1 inhibitor market in NSCLC. That would amount to about $481 million in expected sales for 2021. In all of 2020, Libtayo netted Regeneron $348.2 million.
Porgres also wrote that the upcoming trial results for the drug in patients with lower PD-L1 expression could be an even bigger boon for the company. Those data are expected sometime in the first half of 2021.
Fueled by Covid prospects, Chinese vaccine developer scores $230M to upscale the whole pipeline
Amber Tong
Senior Editor
The Covid tides are floating more than US or European boats.
Take Clover Biopharmaceuticals, the Chengdu, China-based developer of a CEPI-funded vaccine that’s just closed $230 million in a Series C. That means the biotech is officially $400 million richer than it was before the pandemic struck — and potentially standing much closer to the commercial market.
“Over the last 12 months, we have grown our headcount from ~175 FTEs in China to now ~500 FTEs across over a dozen countries,” CEO Joshua Liang told Endpoints News in an email.
It’s also taken a vaccine candidate through early human studies, testing SCB-2019 with both GlaxoSmithKline’s and Dynavax’s adjuvants before dropping the collaboration with the pharma giant. The Phase II/III trial is slated to start in the first half of 2021.
All of that puts Clover’s Trimer-Tag technology platform on an accelerated path not unlike mRNA, with a slate of other programs whose prospects now shine brighter with the newfound validation.
For Clover, the next priorities will be on other vaccines — including multivalent ones against SARS-CoV-2 variants — as well as cancer therapies (in fact, the first compound it put in the clinic back in 2018 was an oncology drug).
Their platform, Liang explained, is a new way of making protein-based vaccines by specifically targeting viruses that have “naturally trimeric spike antigens.”
“These viruses utilize these trimeric spikes to bind to receptors on our cells (such as ACE2 for SARS-CoV-2) and gain entry to replicate and infect us,” he wrote. “Thus, in order to induce a neutralizing and protective immune response against the virus, the vaccine antigen should preserve the native trimeric structure of the spike protein. Our research has demonstrated that compared to non-native conformations of the spike protein (such as dimeric spike protein), our S-Trimer induces around 15-fold higher levels of neutralizing antibodies.”
The resulting vaccines can remain stable under standard refrigeration of 2 to 8 degrees Celsius, he added, and store at least two months at room temperature.
With the vaccine supply deficit “readily apparent” even in places where they are being rolled out, Clover reckons there’s plenty of need to be served around the world. The company will offer its jab to the COVAX mechanism for distribution if it’s authorized, Liang said, and they will be ready with capacity to produce over 1 billion doses annually, starting from its existing commercial-scale manufacturing site in Changxing, China.
“The pandemic has affected the entire world, not just the developed world,” he noted.
GL Ventures — a unit of Hillhouse Capital — and Temasek co-led the Series C, with participation from Oceanpine Capital, OrbiMed and existing investor Delos Capital.
2/12 finished enrollment: U.S. NIH Grant/Contract PENNVAX-GP, INO-6145, INO-9012, CELLECTRA® 2000 Therapeutic Vaccination in Treated HIV Disease at UCLA, UCSF P1/2
Status: Active, not recruiting. Enrollment: 56 [Actual].
Other Study ID Numbers:
DAIDS-ES 38409
U01AI131296 ( U.S. NIH Grant/Contract )
Estimated Primary Completion Date :
December 1, 2021
Sponsors and Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)
University of California, Los Angeles
Inovio Pharmaceuticals
Study Officials: Steven Deeks, MD
Principal Investigator
University of California, San Francisco
https://clinicaltrials.gov/ct2/history/NCT03606213?A=5&B=6&C=merged#StudyPageTop
Our program is inspired by the recent success of VGX-3100 (Inovio), a DNA therapeutic vaccine for HPV that leads to histopathologic regression of pre-malignant lesions in people and is associated with a potent, sustained boost to HPV-specific CD8+ T cell populations. A closely related multi-clade gag/pol/env DNA vaccine administered with an IL-12 DNA plasmid (PENNVAX, Inovio) has been studied for HIV prevention and is known to be both safe and highly immunogenic. In a randomized placebo-controlled study we will compare the immunogenicity and anti-reservoir activities of gag/pol DNA versus gag/pol/env DNA (both administered with IL-12). We will determine for the first time in established HIV disease whether presence of env in a DNA vaccine blunts T cell responses to more conserved Gag-specific and Pol-specific epitopes. We will also determine if Env-specific responses (which will presumably be mediated by antibodies and ADCC) have a measurable effect on reservoir.
Official Title: Safety, Immunogenicty and Anti-Reservoir Activity of an Electroporation-Administered HIV DNA Vaccine Encoding GAG, POL and ENV Proteins With IL-12 Plasmid in HIV-Infected Adults on Antriretroviral Therapy.
Brief Summary:
The central premise of our program is that durable control of HIV in the absence of antiretroviral therapy ("remission") will require the generation of de novo potent and sustained HIV-specific CD8+ cell responses that target evolutionarily conserved epitopes.
Locations:
University of California, Los Angeles
Los Angeles, California, United States, 90025
Zuckerberg San Francisco General Hospital (ZSFG)
San Francisco, California, United States, 94110
Ino to Initiate VGX-3100 P3 trials for VIN/AIN; Attain orphan drug designations in 2021, pg 23/45 of “Powering a New Decade of DNA Medicines January 2021“ in INVESTORS & MEDIA, Download Investors Presentation.
2/21/21 P2a MERS INO-4700, CELLECTRA™ 2000 starts 2/26/21 in Jordan, Lebanon funding by CEPI $56M
INOVIO previously received a $56 million grant from CEPI in 2018, under which the company is developing vaccine candidates for Lassa fever and Middle East Respiratory Syndrome (MERS). INOVIO and CEPI are committed to making a vaccine available as soon as possible for emergency use as a stockpile product post-Phase 2 testing.
Dr. Kim added, "This is the same device [CELLECTRA™ 2000] being used to deliver our DNA vaccine candidate, INO-4800, in the Phase 2 segment of our INNOVATE Phase 2/3 COVID-19 trial. We are grateful to CEPI for the continued support and confidence in our vaccine programs.”
Brief Summary:
The purpose of this Phase 2a, randomized, blinded, placebo-controlled, multi-center study is to evaluate the safety, tolerability and immunogenicity of INO-4700 administered by intradermal (ID) injection followed by electroporation (EP) using the CELLECTRA™ 2000 device in healthy adult volunteers for Middle East Respiratory Syndrome Coronavirus (MERS-CoV) infection. This study is divided into 2 parts: Part 1- dose finding stage and Part 2- dose expansion stage.
Last Update Posted: February 21, 2021 [Actual]
Estimated Study Start Date :
February 26, 2021
Estimated Enrollment :
542 participants
Study Officials: Mammen P. Mammen, Jr., MD, FACP, FIDSA => Bonaventure Orizu, MD
Study Director
Inovio Pharmaceuticals
Locations: Jordan
Pharmaceutical Research Center / Jordan University of Science and Technology
Irbid, Jordan, 22110
Lebanon
American University of Beirut Medical Center
Beirut, Lebanon
Hammoud Hospital University Medical Center
Saida, Lebanon
https://clinicaltrials.gov/ct2/history/NCT04588428?A=4&B=6&C=merged#StudyPageTop
COVID-19 vaccine developers to benefit from supply constraints and uneven distribution
Feb. 18, 2021 6:45 AMAstraZeneca PLC (AZN)MRNA, PFE, BNTXBy: Dulan Lokuwithana, SA News Editor
At 6 – 7B doses for 2021, the estimated COVID-19 vaccine production across the world for 2021 is enough to cover only less than half the global population by the year-end, The Wall Street Journal reported.
The projections by Seth Berkley, chief executive of GAVI, a global vaccine alliance, assume two doses required by most vaccines to complete full immunization.
Inequitable distribution
However, driven by a disproportionate impact from the pandemic, the developed markets home to only ~18% of the world’s population have already claimed 57% of known vaccine purchases, according to UBS estimates.
Canada leads the pack with purchases at ~6x its requirement followed by the U.K. and the U.S. each with agreements for over 4x the requirement while the EU has signed up for more than 3x the doses it requires, according to data from Duke University.
While ~12% of the U.S. population has received at least a single dose of COVID-19 vaccine, only 1.5% and 0.1% of the population in Asia and Africa have received the vaccine, respectively according to Our World in Data, a project from Oxford University.
After the pandemic drove more than 100M people back to extreme poverty, the disparity in vaccine distribution will slow the global economic recovery while giving the virus more opportunities to mutate in those populations with no COVID-19 protection, the experts warn.
Covax, the WHO-led initiative to promote equitable access to COVID-19 vaccines, aims to cover 27% of the population in 92 eligible countries by the end of 2021, mostly in the second half of the year.
Opportunities for developers
That too depends on the vaccine developed by AstraZeneca (NASDAQ:AZN) and the University of Oxford. However, the vector-based vaccine was found to lack efficacy against the new variant first detected in South Africa. The company is working on an updated version of the vaccine against the variant, but that is unlikely to be ready before the autumn.
Virus mutations will offer opportunities to developers of second and third generation COVID-19 vaccines to prove their worth against emerging strains and the established players such as Moderna (NASDAQ:MRNA), Pfizer (NYSE:PFE)/BioNTech (NASDAQ:BNTX) to come up with updated booster shots.
Meanwhile, the supply constraints are likely to ease as vaccine candidates with a comparable level of efficacy to authorized vaccines but with more convenient dosing regimens and storage, requirement seek the regulatory approval.
Johnson & Johnson (NYSE:JNJ) has already applied for regulatory approval for its single-dose vaccine candidate in both the U.S. and Europe and multiple regulatory agencies have started the rolling review of the protein-based vaccine candidate from Novavax (NASDAQ:NVAX).
Related tickers: Ocugen (NASDAQ:OCGN), Inovio (NASDAQ:INO), CureVAC (NASDAQ:CVAC), VBI Vaccines (NASDAQ:VBIV)
2/21/21 Completed w/ Printed Detailed Result: A Study of INO-3112 DNA Vaccine With Electroporation in Participants With Cervical Cancer P1/2a. A PR forthcoming?
https://clinicaltrials.gov/ct2/history/NCT02172911?A=14&B=15&C=merged#StudyPageTop
MedicalResearch Interview w/ JS, Sr VP Clinical Dev: 22 FEB GLIOBLASTOMA: INOVIO’S NOVEL COMBINATION OF DNA MEDICATION PLUS IMMUNOTHERAPY BOOSTS SURVIVAL
Posted at 16:02h in Author Interviews, Brain Cancer - Brain Tumors, Cancer Research, Immunotherapy, Pharmaceutical Companies by Marie Benz MD FAAD
MedicalResearch: What is the background for this technology? Would you tell us a little about the brain tumor, Glioblastoma Multiforme? How common is it, whom does it primarily affect?
Response: Glioblastoma (GBM) is the most common malignant brain tumor, affecting more than 10 thousand people each year in the United States. Most people diagnosed with GBM are above the age of 60 years, although GBM can be diagnosed at any age, including in children and young adults. Despite decades of research, GBM remains almost universally fatal. GBM is a tumor of the glial cells of the brain, and current therapies are directed at removing tumor with surgery and killing residual tumor cells with radiation and chemotherapy.
More recently, with the introduction of immunotherapies such as immune checkpoint inhibitors (ICI) for the treatment of cancer, clinical studies have tried to add this promising technology to the treatment of GBM. Unfortunately, despite success in other types of cancer, ICIs have not demonstrated any clinical benefit in treating GBM. Newer clinical studies aim at introducing a combination of newer therapies together to try to tackle this terrible disease, and INOVIO’s GBM-001 study is one such example of an innovative approach to treating GBM.
MedicalResearch: What are the main findings of the studies of INO-5401, in combination with INO-9012, Regeneron’s PD-1 checkpoint inhibitor Libtayo® (cemiplimab), radiation and chemotherapy in the treatment of glioblastoma?
Response: In INOVIO’s landmark GBM-001 study, we’ve combined the DNA medicines INO-5401, DNA plasmids encoding for the known tumor antigens human telomerase (hTERT), Wilms Tumor-1 (WT-1), and prostate specific membrane antigen (PSMA), together with our DNA plasmid INO-9012, encoding for human interleukin-12 (IL-12), together with the programmed cell death receptor-1 (PD-1) inhibitor cemiplimab (Libtayo®), being co-developed by Regeneron and Sanofi, with radiation and chemotherapy, in order to build a cancer antigen-specific T cell repertoire that is activated against GBM cells. These novel treatments work together, in combination with standards of care therapy (radiation and temozolomide).
In our GBM-001 study, we were able to successfully combine these novel medicines together, and to demonstrate an immunological response to the antigens encoded within INO-5401, in the peripheral blood of patients on the trial. More importantly, we were able to show promising evidence of clinical activity, prolonging progression-free survival at 6 months, and overall survival at 12 and 18 months, when compared with historical controls (Stupp, 2005; Hegi, 2009).
MedicalResearch: What should readers take away from your report?
Response: This is a first-of-its-kind clinical trial in which a DNA medicine encoding for tumor-specific antigens is combined with an ICI, and given together with the standard of care, in patients with newly diagnosed GBM. This study shows clear evidence of an immunological response to this novel combination and demonstrates the potential importance of T cells against GBM. The combination of INO-5401 with INO-9012 and cemiplimab, together with the standards of care of radiation and chemotherapy, demonstrated an acceptable safety profile, and we look forward to continued analysis of our clinical data and to next clinical steps.
MedicalResearch: What other cancers might be amenable to treatment innovation with this platform?
Response: INOVIO has previously studied DNA medicines similar to, if not in part identical to, INO-5401 in prostate cancer and in a variety of solid tumors, such as pancreatic cancer, lung cancer, and colon cancer. In these studies, we were able to show an immune response to our DNA medicines, and a correlation between immune response and potential clinical improvement. Given the prior evidence of immune response in these studies, and our current and ongoing clinical cancer studies, there is no reason to believe that other cancers would not also be amenable to either identical, or similar therapies. INOVIO’s DNA medicines platform allows for the adaptation of its plasmids to address essentially any tumor antigen for which the DNA sequence is known, and allows for incorporation of that sequence into a synthetic DNA plasmid that can be provided to the patient – in combination with our CELLECTRA® device – in order to generate a robust immune response that we hope is capable of killing tumor cells and ultimately extending survival.
Interestingly, our DNA medicines are not limited to plasmids encoding for tumor antigens. We are continuing to innovate in the cancer therapeutic space, and newer pre-clinical programs have designed DNA-encoded plasmids that can build fully functional proteins, such as monoclonal antibodies, or bi-specific T cell antibodies. Monoclonal and bi-specific antibodies have been approved for the treatment of various cancers but producing and dosing such antibodies often proves challenging. INOVIO hopes to solve these problems using its DNA-encoded antibody program. Importantly, the first of these novel medicines, encoding for an antibody against the Zika virus, is a first-in-human, first-in-class molecule already in the clinic in clinical trials, and we look forward to expanding trials like these in the future.
MedicalResearch: Is there anything else you would like to add?
Response: We are excited, privileged and proud to be part of a true revolution in the treatment of cancer. Being able to turn on the human immune system – to use the body as its own champion and warrior in the fight against cancer – has long been the goal of cancer physicians and scientists. By using INOVIO’s DNA medicines, coupled with our CELLECTRA® device, we are finding ways to harness the power of our own protective cells, while providing a safe and tolerable therapeutic modality that aims to improve survival and overall well-being in treating human diseases.
Citation: Abstract presented at Society for Neuro-Oncology 2020 Annual Meeting
Title: “INO-5401 and INO-9012 delivered intramuscularly (IM) with electroporation (EP) in combination with cemiplimab (REGN2810) in newly diagnosed glioblastoma”
Presenting Author: Dr. David Reardon
https://medicalresearch.com/cancer-_-oncology/glioblastoma-inovios-novel-combination-of-dna-medication-plus-immunotherapy-boosts-survival/56752/
Are Short-Sellers Right About Inovio?
This straggler in the vaccine race is still facing some struggles -- but there are a couple of bright spots.
Adria Cimino
(TMFAdriaCimino)
Feb 21, 2021 at 6:26AM
Ino started the coronavirus vaccine race on the right foot. Investors cheered last spring when the company became one of the first to bring a coronavirus vaccine candidate into human trials. And then Inovio lost steam. Some investors were disappointed by a lack of detail in the phase 1 clinical trial report. Later in the year, the U.S. Food and Drug Administration (FDA) placed a partial clinical hold on its phase 2/3 trial.
Inovio is no longer a leader from a timeline perspective. Pfizer (NYSE:PFE) and Moderna (NASDAQ:MRNA) have brought vaccines to market. And Johnson & Johnson (NYSE:JNJ) and Novavax (NASDAQ:NVAX) are requesting regulatory authorization. Meanwhile, short-sellers are betting that shares of Inovio -- up more than 56% since the start of the year -- are going to fall. Are they right?
Inovio's timeline
Let's take a look at the timeline first. Inovio launched its phase 2 study in early December 2020. At that time, the FDA lifted the partial clinical hold on phase 2 but maintained it on the phase 3 portion of the trial.
The FDA originally initiated a partial hold because it had questions about the phase 2/3 study and Inovio's administration device, which is called Cellectra. The handheld device uses electrical pulses to deliver Inovio's vaccine candidate into skin cells. Inovio has said it will answer all of the FDA's questions during the phase 2 portion of the trial. The FDA has 30 days to issue a response from that point. Even if both parties make an effort here, the big risk is that the hold will delay the start of phase 3.
Inovio hasn't provided an update. But we may expect more news when the company reports earnings on March 1.
Now, let's turn to the data. In December, Inovio said it had published phase 1 data in The Lancet's EClinicalMedicine journal. Investors' earlier concern had been a lack of detail regarding the production of neutralizing antibodies. In the report, Inovio said 84% of participants given the higher dose used in the trial developed neutralizing antibodies. On this metric, Inovio still lags behind rivals like Moderna and Pfizer. Those vaccines produced neutralizing antibodies in all participants. And antibody levels were higher than those of recovered coronavirus patients.
On a brighter note, Inovio reported T-cell responses in 100% of volunteers in the higher dose group. T-cells, known for killing infected cells, recognized various parts of the spike protein. The spike protein is what the coronavirus uses to infect healthy cells. Safety data was another positive. Inovio reported no serious adverse events.
Inovio versus rivals
At this point, Inovio's results don't look as strong as those of its more advanced competitors. Inovio is lagging behind from a timeline and data perspective. But new data could still save the day, in two ways: If the T-cell responses prove to be as important as neutralizing antibody levels, and if the vaccine can handle new strains. Phase 2 information should offer us a clearer picture.
Finally, one other feature may help bring Inovio's vaccine to the forefront. It may be kept at room temperature for more than a year. This is a big plus when it comes to storage and transportation. By comparison, Pfizer's vaccine must be kept at freezing temperatures and Moderna's requires refrigeration.
The ride has been bumpy for Inovio so far. And risk remains high. But if the FDA lifts the partial clinical hold and phase 2/3 data are strong, Inovio still may have a chance to carve out a spot in the coronavirus vaccine market.
So, what are the short-sellers saying? Short positions make up about 21% of Inovio's float. That's a decent percentage of investors betting on the stock's decline. But that's actually down from a peak of nearly 36% a few months ago.
Investors may be regaining confidence in Inovio. Ultimately, though, short-sellers won't determine what happens with Inovio's stock. The clinical trial results will. Until Inovio reports more data, it's best to be cautious. But, considering the positive points I mentioned above, we might do so with a bit more optimism than several months ago.
Can I choose my covid vaccine? Strong opinions on Oxford vs. Pfizer emerge in U.K.
By William Booth and Karla Adam
Feb. 21, 2021 at 4:28 p.m. EST
LONDON — It's the ultimate first-world problem. While more than 130 countries are still waiting for coronavirus vaccines, the wealthiest nations have doses on offer from multiple makers, and people rolling up their sleeves want to know: Can I choose which shot I get?
In Britain, the options today are the homegrown Oxford-AstraZeneca jab, “the English one,” or the Pfizer-BioNTech vaccine, “the posh one.” Doctors’ offices describe the phones ringing with patients certain which is better, or best, for them.
The choice is complicated by the fact that there is not supposed to be any choice. There is no private option in Britain for this. The vaccines are bought, distributed and deployed by the state-funded National Health Service, which serves all, rich and poor, free at the point of service — with no one allowed to jump the queue or pick and choose.
The official NHS policy is to take what is offered, or as a spokesman put it: “It will either be Pfizer or Oxford at a site depending on deliveries. People can choose their preferred site but not their vaccine.”
But, as in any system, there are end runs and insider plays, where staff who work at health clinics, for example, may tip off family and friends to what’s on offer. Some folks have resorted to “hospital hopping,” making or canceling vaccination appointments based on rumors of which shot is being injected where.
British regulators have said both vaccines are just great. “Both give very high protection against severe disease” and?“both vaccines have good safety profiles,” the Joint Committee on Vaccination and Immunization reported. The government has ordered 140 million doses of those two, plenty to vaccinate the entire adult population of 54 million people by the fall. (Britain has also authorized Moderna, but its 17 million doses won’t begin to arrive until the spring.)
At issue for public health services are: efficacy, cost, supply, ease.
But consumers may also consider nationalism, branding and buzz — what they’ve heard from friends or read on the Internet.
The question of choice hasn’t been much of an issue in the United States, where the two vaccines in use — Pfizer and Moderna — are basically equivalent, both “Made in USA,” both relying on the same technology and producing the same results in clinical trials. A U.S. regulatory decision on Oxford-AstraZeneca is expected in April.
Washington Post coronavirus tracker
But because the United Kingdom and the European Union have already authorized all three, and because there’s greater distinction between Oxford and the others, some here have formed strong opinions about which they want, and which they don’t.
Pfizer is more expensive, it uses a sexy new platform to deploy messenger RNA, and it appears to work somewhat better at preventing mild to moderate cases.
In clinical trials, with two full doses, Pfizer was 95 percent effective at stopping symptomatic covid-19. So was Moderna. Oxford’s data has been messier. Its trials in the U.K. found it to be 62 percent effective. Using a bit more data, British regulators calculated that a two-dose regimen produces a 70 percent reduction in symptomatic disease. The European Medicines Agency put the number at 60 percent.
On the most-watched public affairs show in Britain, the BBC host Andrew Marr asked the question on many minds: “If I am sitting at home and my doctor rings me up and says, ‘Good news Andrew, we can get you a vaccine!’ At the moment, looking at the results that have come out, I might well say, ‘Excellent, can I have the Pfizer one or the Moderna one rather than the AstraZeneca one?’ Because their efficacy rate is much higher.”
That’s the sense emerging across Europe, where French health-care workers and Italian teachers are demanding the Pfizer or Moderna vaccines, and Germany is reporting no-shows at Oxford vaccine appointments.
The hesitation was reinforced after South African researchers found that the virus variant first identified there may elude the Oxford-AstraZeneca vaccine. South Africa has halted its AstraZeneca rollout.
About a dozen countries in Europe are also avoiding the Oxford vaccination for people over 65, noting that early trials didn’t include enough volunteers in that age group to prove effectiveness.
But many in Britain prefer the Oxford brand. They’ve seen its inventors, the confident Sarah Gilbert and the calming Andrew Pollard, on television — and to them, the Oxford option just feels right.
Paul Williams, a doctor and former Labour Party member of Parliament, told The Washington Post that some patients were declining Pfizer appointments, saying “No thanks, I’ll wait for the English one.”
Williams said he thought the preference was generated by Prime Minister Boris Johnson’s bully endorsement of the homegrown product “from our brilliant British scientists.” Wags suggested vaccine doses should feature a Union Jack on the vials, even though AstraZeneca is a British-Swedish pharmaceutical company.
Pfizer, incidentally, is a U.S.-based pharmaceutical giant, but the vaccine was developed by a German Turkish couple running a small cutting-edge company called BioNTech. So to some in Europe, the Pfizer shot is “the German one.”
Both jabs have limited transient side effects, common to vaccines, such as pain and tenderness at the injection site, headache, tiredness, muscle pain, a general feeling of being unwell, chills, fever, joint pain and nausea.
Early on, the Pfizer vaccination produced a few episodes of extreme allergic reaction among those who are very vulnerable, and that turned some off the vaccine. Social media is filled with stories about how the Oxford or Pfizer shot made posters feel the day after their first dose.
Andrew Pollard, a leader of the Oxford vaccine team, told The Post, “For me, personally, I would have whichever vaccine offered, because the most important thing with vaccination is to have the dose in your arm.”
Pollard cautioned against fixating on precise numbers in early clinical trials. “The problem with the trials, unless you run the trials head-to-head, you don’t really know whether a 95 percent figure on trial and 62 percent in another trial mean the same thing,” he said.
Gilbert, the co-developer of the Oxford shot, confessed that “there were days when I just don’t want to read the newspapers because it’s just more AstraZeneca bashing and I don’t really understand why that is.”
She said that “real world head-to-head results” comparing Pfizer and Oxford are coming soon in Britain. “Then we'll see how it looks.”
Anesthesiologist Gareth Greenslade got the Pfizer jab at the hospital where he works. His wife, a nurse, got the AstraZeneca vaccine at a vaccination center in Bristol.
They would have happily taken either, he said. But he confessed he wanted Pfizer “because it is a new technology and doctors are geeky.”
As he put it, the Oxford-AstraZeneca vaccine is “fairly traditional,” made from a weakened chimpanzee cold virus that carries a snip of DNA to mimic the viral spike protein. “So from the point of view of stopping you from dying, AstraZeneca does it,” Greenslade said.
But he liked to imagine the Pfizer dose inside him, built upon new mRNA biotech — “It’s just such an elegant idea to teach the cells to produce a harmless protein, and then it all goes away again, but the immune system is sitting there, like a coiled spring.”
Asked if people should get a preference, Greenslade said, “In an ideal world, yes.”
But, he said, the Pfizer shot, needing specialty freezers for transport and storage, mean that it’s more likely to be found at large hospitals, and the AstraZeneca one is more likely to be found at smaller venues where the vaccine can be popped into a normal fridge — which is another way to guess which vaccine might be offered where.
For some, these discussions of choice are frustrating. Just hurry up, they say.
A quarter of the population has gotten at least one vaccine dose, and coronavirus cases have been declining dramatically. Yet Britain remains in its third national lockdown. The country has the highest per capita death toll in Europe over the course of the pandemic, and on many days is the worst in the world. Its health system is battered and has been overwhelmed. Patients needing routine surgeries have been put on year-long waiting lists.
Linda Bauld, professor of public health at the University of Edinburgh, said people being allowed to select their preferred vaccine clashed with Britain’s model of nationalized health care.
“Supply is a challenge and will continue to be a challenge. So it’s not fair to others to have that choice, in a publicly funded system,” she said.
If people were to insist on one type of vaccine, Bauld said, “they may be taking it from someone else, or taking someone’s second dose. That’s at odds with the universal health-care system in place.”
https://www.washingtonpost.com/world/europe/covid-vaccines-choice-pfizer-astrazeneca/2021/02/20/0beaceb0-5f2f-11eb-a177-7765f29a9524_story.html
Mcsnacks: phase 3 only requires 1 dose, Unless phase 2 has less than desired results.
stocktwits.com/Uncle1Sam/message/292793541
This possibility deserves a headline on its own.
fiercepharma.com/pharma/bring-boosters-studies-show-pfizer-moderna-covid-vaccines-are-less-protective-against-south
In early January, researchers from the University of Texas and Pfizer published a preprint study suggesting that Pfizer’s COVID-19 vaccine could protect against a mutation discovered in the U.K. and South Africa. Two weeks later, though, news emerged that Pfizer and its partner BioNTech were working on booster shots to protect against new variants.
Now there’s more evidence that Pfizer’s vaccine—as well as the other authorized mRNA vaccine from Moderna—will need to be updated to fend off aggressive new variants of COVID-19. The data are raising concerns among some analysts of "breakthrough" cases of COVID-19, even in vaccinated people, and the potential for more lockdowns this summer.
In a letter published in The New England Journal of Medicine Wednesday, Pfizer and the University of Texas said a lab study showed the vaccine was about two-thirds less potent against the South African variant of COVID-19 than it was against the original virus.
Moderna also published a letter about its vaccine in NEJM, explaining that its scientists tested its COVID vaccine against several variants, including those found in the U.K., South Africa and Denmark. They found a sixfold decrease in neutralizing antibodies when they tested the vaccine against “the full panel of mutations,” they reported.
Decreased potency doesn't necessarily mean the vaccines are less protective; lab tests don't fully reflect how the shots perform in the real world. One missing piece of information is T-cell activity, which might persist despite mutations, the analysts said. Just how protective they are against the variants remains unknown at this point.
Both companies used serum samples taken from participants in their original vaccine trials to perform the studies. That presented some limitations, they said in their letters, making it impossible to say for certain just how effective the vaccines will be if the new variants take over and start spreading widely. Still, the studies were enough to raise concerns among Wall Street analysts.
C-2K picx used at Walter Reed Army Institute of Research to 2nd jab MrBulll12 on 2/4/21
https://stocktwits.com/MRBULLL12/message/283775807
Thermo Fischer box in the vaccination room
https://stocktwits.com/MRBULLL12/message/283779645
MrBulll12 at Walter Reed Army Institute of Research
https://stocktwits.com/MRBULLL12/message/283711349
4800 P2 "Active, not recruiting" means Enrollment: 6578 [Anticipated] => 401 [Actual] received 1st dose. P2 finished enrollment. The extra 1 must be over 65 who is harder to get.
https://clinicaltrials.gov/ct2/history/NCT04642638?A=5&B=6&C=Side-by-Side#StudyPageTop
Last Update Submitted that
Met QC Criteria: February 19, 2021
Last Update Posted: February 22, 2021
[Estimate ]
Due Dilligence
Got my 2nd dose Phase 2 (1/21/21). Feeling great. No issues
rdawgstonks
@Uncle1Sam 1/26/21 I don't receive my 2nd dose till 2/10. it was supposed to be 2/8 but they asked me to come back 2/10 because 'they would prefer not spreading people out and having them all come in one day'
Gorester
07:51 AM 1/30/21
I had my 6 week blood work completed on my phase 2 trial last week.
I think the phase 3 portion will begin in March.
Just my opinion.
obx4me
08:21 AM 1/30/21
@Gorester my 6 week blood draw is Monday. Was supposed to be last week but moved date to Monday 2/1/21 they said that was OK still in the window
2/1/21 Scott E
@inoviolt My wife had her first INO-4800 shot today, Phase 2. I had my second dose 10 days ago. No side effects to report.
Various responses:
“ Wow, why such a delay. If INO is struggling to find volunteers for P2, how are they going to do that for P3? Mind you, they don't take everyone. I tried and was not qualified. Wonder whether they got other plans.
if her first dose was today Feb 1st, second dose will be Mar 1st.
two weeks later labs to be drawn... that puts us to Mar 15th.
Hoping that she gets the real thing.
This solidifies phase 2 completion mid to late March then 30 days for FDA to respond. Thanks for volunteering!
All participants in China just had their 2nd dose; but China will draw blood in 30-days instead of 14-days - kinda odd. I guess 4-weeks for Cellular response. We may get EUA from China based on P2 or start recruiting P3 in March - either way, it's good news
Canada, but Chinese. They were fully enrolled before Jan 1st 2021 so the timeline is correct. We're super fast and have no problem recruiting participants.”
2/4/21 MRBULLL12
@TrentonLaw no they did not. I was told this morning I was among the first to be vaccinated at this site (Walter Reed in MD). They’ll be giving the 2nd to a number of people this month
About to get my 2nd dose in the phase 2 trials. Will post on any major updates
MrSteel
2/18/21 San Antonio
fairly generic trading day, nothin to really worry. my 2nd dose is scheduled for 2/22. still not in this, but i like the way its holding.
DelawareInTheHouse
2/10/21, 04:22 PM
I gave 7 vials of blood today to complete my 6 week lab work.
John 1/25/21
I was given the option to receive a 3rd dose of 4800 last week in the KY phase 1 trial. (1st dose was July 6, 2nd was Aug. 3 2020. I accepted / no side effects.
John 2/1/21
They drew my 67 year old blood again yesterday - two weeks after my P1 3rd dose of INO 4800
2/12 Therapeutic Vaccination in Treated HIV Disease P1/2. Status: Active, not recruiting. Enrollment: 56 [Actual]. Biological: PENNVAX-GP
Biological: INO-6145
Biological: INO-9012
Device: CELLECTRA® 2000
Other Study ID Numbers:
DAIDS-ES 38409
U01AI131296 ( U.S. NIH Grant/Contract )
Estimated Primary Completion Date :
December 1, 2021
Sponsors and Collaborators
Steven Deeks
National Institute of Allergy and Infectious Diseases (NIAID)
University of California, Los Angeles
Inovio Pharmaceuticals
Study Officials: Steven Deeks, MD
Principal Investigator
University of California, San Francisco
Locations:
University of California, Los Angeles
Los Angeles, California, United States, 90025
Zuckerberg San Francisco General Hospital (ZSFG)
San Francisco, California, United States, 94110
https://clinicaltrials.gov/ct2/history/NCT03606213?A=5&B=6&C=merged#StudyPageTop
Official Title:
Safety, Immunogenicty and Anti-Reservoir Activity of an Electroporation-Administered HIV DNA Vaccine Encoding GAG, POL and ENV Proteins With IL-12 Plasmid in HIV-Infected Adults on Antriretroviral Therapy.
Brief Summary:
The central premise of our program is that durable control of HIV in the absence of antiretroviral therapy ("remission") will require the generation of de novo potent and sustained HIV-specific CD8+ cell responses that target evolutionarily conserved epitopes. Our program is inspired by the recent success of VGX-3100 (Inovio), a DNA therapeutic vaccine for HPV that leads to histopathologic regression of pre-malignant lesions in people and is associated with a potent, sustained boost to HPV-specific CD8+ T cell populations. A closely related multi-clade gag/pol/env DNA vaccine administered with an IL-12 DNA plasmid (PENNVAX, Inovio) has been studied for HIV prevention and is known to be both safe and highly immunogenic. In a randomized placebo-controlled study we will compare the immunogenicity and anti-reservoir activities of gag/pol DNA versus gag/pol/env DNA (both administered with IL-12). We will determine for the first time in established HIV disease whether presence of env in a DNA vaccine blunts T cell responses to more conserved Gag-specific and Pol-specific epitopes. We will also determine if Env-specific responses (which will presumably be mediated by antibodies and ADCC) have a measurable effect on reservoir.
If REVEAL 1 top line readout in 2Q is excellent, I expect some kind of collaboration and licensing partnership to follow with large upfront payment due to huge markets, milestones bonus, and low double digit royalty.
TTM depends on REVEAL2 updated 2/4/21 adding SA site.
University of Cape Town
[Not yet recruiting]
Cape Town, Western Cape, South Africa, 7925
Contact: Rene WilliaStudy Coordinatorms Rene Williams +27216501651 rene.williams@uct.ac.za
Principal Investigator: Nomonde Mbatani
Read my post “ 2/9 With checkpoints, the cancer vaccine discussion "is back on the table," and "there is value to be unlocked," predicts Maxim’s McCarthy. He lists Heat Biologics, Sellas Life Sciences (SLS) and Inovio (INO) as cancer vaccine plays.”
3 sites in Brazil, 4 sites in US have finished recruiting.
Brazil, Bahia
Associação Obras Sociais Irmã Dulce Hospital Santo Antônio
[Active, not recruiting]
Salvador, Bahia, Brazil, 40420-000
Brazil, Goiás
Hospital das Clinicas de Goiânia
[Active, not recruiting]
Goiânia, Goiás, Brazil, 74605-050
Brazil, Paraná
Hospital Erasto Gaertner
[Active, not recruiting]
United States, Georgia
Augusta University
[Active, not recruiting]
Augusta, Georgia, United States, 30912
United States, Maryland
Unified Women's Clinical Research - Hagerstown
[Completed]
Hagerstown, Maryland, United States, 21740
United States, New Jersey
New Jersey Medical School
[Active, not recruiting]
Newark, New Jersey, United States, 07103
Unified Women's Clinical Research - Morehead City
[Completed]
Morehead City, North Carolina, United States, 28557
Maxim: “cancer vaccine discussion "is back on the table," and "there is value to be unlocked," lists Ino as cancer vaccine plays
2/9/21 Heat data puts cancer vaccine discussion 'back on the table,' says Maxim 10:52 HTBX, SLS, INO Heat Biologics (HTBX) shares are up 60% this morning on positive interim survival data from the company's ongoing Phase 2 trial of HS-110 and nivolumab in both previously treated checkpoint inhibitor-naive and CI-treated advanced non-small cell lung cancer patients, Maxim analyst Jason McCarthy tells investors in a research note. One-year survival rate for Cohort A was 61.7%, which compares favorably to the 50.7% one-year survival rate noted with single-agent nivolumab therapy in the CheckMate 057 study, says the analyst. McCarthy adds that while a lot of focus has recently been placed on Heat's Covid vaccine candidate, the company's core oncology programs are continuing to make progress. With checkpoints, the cancer vaccine discussion "is back on the table," and "there is value to be unlocked," predicts McCarthy. He lists Heat Biologics, Sellas Life Sciences (SLS) and Inovio (INO) as cancer vaccine plays. McCarthy keeps a Buy rating on Heat Biologics with a $22 price target.
DISRUPTOR' GAINING STEAM: Oppenheimer analyst Hartaj Singh initiated coverage of Inovio Pharmaceuticals (INO) with an Outperform rating and $35 price target. Inovio's COVID-19 vaccine has a "differentiated profile and is moving closer to the finish line," Singh tells investors in a research note titled "A DNA Medicines Disruptor Gaining Steam." The company also has a "unique cancer vaccine with intriguing early-stage efficacy" in glioblastoma, adds the analyst. Singh says that while COVID-19-focused INO-4800 has been the high-profile candidate, Inovio's overall DNA platform "should not be overlooked." The analyst is bullish on the company's approach. INO-4800 has a better safety and tolerability profile that could generate higher uptake in a low-risk population, easier storage favored by stockpile, and potential flexibility to adjust for mutations, Singh contends.
Pinned under Max Pain $13.5 2/19. “Last week I was saying February OPEX was going to impact all stocks because of big time call options having been sold with the euphoria meme craze. this is the week you add your favorites.. We could see a capitulation panic sell tomorrow followed by a rip higher into close.” By @CovidObsessed, Disruptive Investor
Law360 (February 16, 2021, 11:08 PM EST) -- Biotechnology firm Inovio Pharmaceuticals Inc. and a cohort of company executives must face slightly trimmed class action claims alleging they misled the public about a coronavirus vaccine they purport to have in the works, a Pennsylvania federal judge ruled Tuesday.
In a 26-page order, U.S. District Judge Gerald J. Pappert partially granted Inovio's motion to dismiss, scrapping some of the claims based on two press release statements the company and some of its executives made last year, but keeping the majority of the investors' claims intact.
The consolidated suit, which launched March 12 and was most recently amended in September, names as defendants Inovio, its chief executive J. Joseph Kim, its chief financial officer Peter D. Kies and its vice president of biological manufacturing and clinical supply management Robert J. Juba Jr.
In the suit, investors led by Manuel Williams allege that between Feb. 14 and Aug. 10, as the pandemic escalated across the nation, the company made intentionally confusing statements about its work on a COVID-19 vaccine in an attempt to push up its trading price.
"Defendants' ongoing unlawful scheme has caused significant damages to investors and allowed the company to raise over $320 million in stock offerings," the investors claimed in the September version of their suit.
In his order Tuesday, Judge Pappert found that the investors have provided enough evidence at this point in the case to allege that Kim misled the public when he said in February 2020 that Inovio constructed its vaccine within three hours of accessing COVID-19's genetic sequence, causing the company's stock to rise, while the company in March walked that assertion back to say that it had designed a vaccine in three hours, causing the stock to plummet.
Even though Inovio argued that the terms "design" and "construct" are synonymous, Judge Pappert said that issue is a question of fact that can't be resolved in a motion to dismiss.
"By alleging defendants claimed to have achieved something they did not achieve and thereby instilling false confidence in investors, plaintiffs have satisfied their burden of alleging why Kim's statements were misleading," the judge said.
Judge Pappert also found that the investors have adequately pled that Kim acted with scienter when he made the false vaccine "construction" statement, saying they detailed his background and experience in the pharmaceutical industry, suggesting that he would understand the difference between "constructing" and "designing" a vaccine, according to the order.
The investors also adequately pled loss causation, the judge said, finding that they allege Inovio's stock price increased 7.5% after Kim's first vaccine construct claim and 69.7% after his second claim, but that after the company claimed to have only designed a vaccine, its stock tumbled in response.
The judge then found that the investors' claims that Kim misled the public when he made a statement in May about Inovio and its manufacturing partners being able to produce one million vaccine doses by the end of the year are not preempted by the Private Securities Litigation Reform Act's safe harbor provision for forward-looking statements.
The judge found that the investors had alleged that it was a present statement because at the time Kim made the statement, Inovio didn't have the manufacturing capacity to produce that many vaccines by year's end.
While Judge Pappert found the investors had done enough to allege that Inovio and its executives made misleading statements and omissions about the company's manufacturing capabilities, the judge said that wasn't true of an April press release about the company's manufacturing partnership with Richter-Helm Biologics GmbH & Co.
Judge Pappert also rejected the investors' claims regarding a press release Inovio put out in June announcing that its vaccine was included in the federal government's vaccine initiative Operation Warp Speed, saying the investors hadn't shown that Inovio misled the public about receiving government funding for its vaccine when it had actually only been selected to participate in a non-human primate study.
The judge said Inovio never claimed to be receiving vaccine funding and that it disclosed its vaccine had been chosen for the study in the same press release in which it broadly claimed to have been selected for Operation Warp Speed.
"Plaintiffs do not explain how or why a reasonable investor with access to all this information would have thought Inovio would receive government funding for its vaccine," Judge Pappert said. "Even if defendants' claim about being selected for Operation Warp Speed was a misrepresentation, the subsequent disclosure rendered it immaterial and not misleading."
Judge Pappert dismissed with prejudice the claims related to the April press release and the claims related to the June Operation Warp Speed announcement, but kept the rest of the suit intact.
Representatives for the parties did not immediately respond to requests for comment Tuesday evening.
The investors are represented by Darren J. Robbins, Tor Gronborg, Trig R. Smith, Matthew J. Balotta and James E. Barz of Robbins Geller Rudman & Dowd LLP and Lawrence F. Stengel of Saxton & Stump.
Inovio is represented by Patrick Loftus and Matthew S. Decker of Duane Morris LLP and Luke Cadigan and Heather Speers of Cooley LLP.
The case is Patrick McDermid v. Inovio Pharmaceuticals Inc. et al., case number 2:20-cv-01402, in the U.S. District Court for the Eastern District of Pennsylvania.
--Additional reporting by Dean Seal, Matthew Santoni and Emilie Ruscoe. Editing by Regan Estes.
gew59, did-you-cover-at $16.3 yet or wait-until $25? GL
This is one of many reasons hedge funds started short covering. I expect pps to test $18.9 shortly, then $25, $30, $35, ... in addition to tailwind from Reddit’s WallStreetBets revolution.
Can a person be vaccinated fully with a 2 dose RNA vaccine and at a later date be vaccinated with a 2 dose DNA vaccine. And would the DNA vaccine enhance the persons immunity without greater side effects theoretically? YES.
“one attractive feature of DNA vaccines like INO-4800 is that the immunizations could be boosted without significant limitations such as anti-vector responses or dosing-incremented toxicities, and additional boosting with other DNA vaccines have resulted in higher levels of humoral and cellular immune responses without increased toxicity [2, 3, 4, 5]. The INO-4800 Phase 1 safety data further suggest that the vaccine could be a safe booster as there was no increase in frequency of side effects after the second dose compared to the first dose, an important aspect for the safety profiles of SARS-CoV-2 vaccines. Given the uncertainty about the durability of the natural infection or vaccine induced responses against COVID 19 disease, vaccine boosting by a benign approach may be an important way to maintain protection over subsequent epidemic waves of COVID 19. It is also possible that INO-4800 could serve as a useful booster shot for other S protein-targeted vaccine candidates with limitations in boosting ability. In addition, planning is underway to further test if INO-4800 could provide booster immunity for COVID-19 recovered patients whose immunity is reported to wain rapidly. Many such subjects include persons in high risk groups who would especially benefit from longer term immune protection.”
From “Safety and immunogenicity of INO-4800 DNA vaccine against SARS-CoV-2: a preliminary report of an open-label, Phase 1 clinical trial”
in EClinicalMedicine, an open access clinical journal published by The Lancet.
Tesla short sellers lost $40 billion in 2020. Elon Musk made more than triple that.
Elon Musk
@elonmusk
“u can’t sell houses u don’t own
u can’t sell cars u don’t own
but
u *can* sell stock u don’t own!?
this is bs – shorting is a scam
legal only for vestigial reasons
12:34 PM · Jan 28, 2021”
The $40.1 billion in losses by investors shorting Tesla stocks were unlike the losses weathered by any other companies' short investors -- last year or ever -- according to Ihor Dusaniwsky, managing director at S3 and an expert in the subject.
In fact, the losses endured by Tesla shorts were more than the short losses for the next nine companies -- combined. Losses on No. 2 Apple (AAPL) in 2020 came to $6.7 billion, which is only slightly more than Tesla shorts lost in the month of December alone. Amazon (AMZN) cost the shorts $5.8 billion, according to S3.
Tesla has long been a favorite play for short investors, who controlled about 19% of the shares as 2020 began. For all those who believe the company is a paradigm-changing, clean energy leader of unlimited potential, other investors maintain it is an overhyped niche player soon to be overwhelmed by larger, more established automakers.
Many of the shorts were forced to admit defeat last year. About two-thirds of the short positions were unwound during 2020, which in itself was a factor that helped drive Tesla shares higher, as the short investors were forced to buy higher-priced shares to exit their positions.
"It was a gentle tail wind in Tesla's price move all year long," said Dusaniwsky.
But the year ended with short investors still holding roughly 5.5% of Tesla's shares, which equates to a $31 billion bet against the company's future prospects. For comparison, there is $13.3 billion and $10.2 billion currently bet against Apple and Amazon respectively, with shorts controlling less than 1% of each of those companies' stocks.
Melvin Capital, hedge fund that bet against GameStop, lost more than 50% in January
UPDATED SUN, JAN 31 2021 2:36 PM EST
KEY POINTS
Hedge fund Melvin Capital Management lost 53% in January amid a record rally in GameStop, which the fund was betting against.
The heavy losses comes as retail investors piled into popular hedge fund short targets, including the struggling video game retailer.
Shares of GameStop finished last week 400% higher, bringing its total gain this year to 1,625%.
Hedge fund Melvin Capital Management lost 53% in January amid a record rally in GameStop and other stocks the fund was betting against, a source familiar with the matter told CNBC.
The heavy losses come as retail investors piled into popular hedge fund short targets, including the struggling video game retailer. Shares of GameStop finished last week with a gain of 400%, bringing its total return this year to 1,625%. The stock closed Friday's session at $325.
As recently as October it traded under $10. CNBC's Andrew Ross Sorkin reported last week that Melvin Capital closed out its short position in GameStop on Tuesday afternoon after sustaining heavy losses.
Citadel and Point72 infused close to $3 billion into the fund to shore up its finances. Citadel's flagship fund lost less than 1% last week on its investment into Melvin Capital, a source familiar with the matter told CNBC.
Melvin's assets under management now stand at more than $8 billion — including the emergency funding — down from roughly $12.5 billion at the beginning of the year, after certain current investors committed additional capital at the end of the month.
The fund's liquidity is strong and its use of leverage is at the lowest level since the fund's inception in 2014, according to the source.
The Wall Street Journal first reported Melvin's January losses.
Last week’s activity in GameStop extended to other popular short targets, including Bed Bath & Beyond and AMC Entertainment, with retail investors turning to Reddit’s WallStreetBets forum to discuss various trades. The forum has seen its members more than triple in just a week to north of 7 million.
Amid the short squeeze, Robinhood and other brokerages restricted trading in some of the most volatile names, sparking frustration for users who were unable to trade at will.
Robinhood said in a blog post that the central Wall Street clearinghouse mandated a tenfold increase in the firm’s deposit requirements on the week in order to ensure smooth settlement in trades involving the securities experiencing unprecedented volatility.
The meteoric rise in GameStop’s shares has prompted some lawmakers to call on regulatory bodies to intervene.
“We need an SEC that has clear rules about market manipulation and then has the backbone to get in and enforce those rules,” Sen. Elizabeth Warren, D-Mass., told CNBC Wednesday. “To have a healthy stock market, you’ve got to have a cop on the beat.”
Studies Indicating T-Cells May Be Needed For Long-Term Protection From The SARS-Cov-2 Virus
PALM BEACH, Fla., Jan. 28, 2021 /PRNewswire/ -- According to the National Institutes of Health (NIH), the tide in the global fight against COVID-19, the disease caused by the SARS-CoV-2 virus, may soon begin to turn. Last month, three pharmaceutical companies announced promising results from vaccine trials. Countries around the world are now poised to begin the largest mass vaccination campaigns since the 1950s. Researchers led by Dr. Dan Barouch of Beth Israel Deaconess Medical Center used monkeys to look at levels of antibodies and immune cells required to prevent reinfection with the virus. NIH said some questions remain about what types and amounts of immune system components are needed to produce long-term immunity against SARS-CoV-2. This information would be valuable both for tracking the effectiveness of vaccines and designing new ones in the future. It said that This finding suggests that T cells are needed for long-term protection from the virus. "Antibodies alone can protect, including at relatively low levels, but T cells are also helpful if antibody levels are insufficient," Barouch says. "Such knowledge will be important in the development of next generation vaccines, antibody-based therapeutics, and public health strategies for COVID-19."
BMJ. Com reported on a similar test but humans were the patients here, to find out how long the T Cells last after an infection. The results were that Robust cellular immunity persists for at least for six months after even mild or asymptomatic SARS-CoV-2 infection, research has shown. The study of 100 people showed that all had a cellular immune response against SARS-CoV-2 six months after infection although the size of response was 50% higher in those who had experienced symptomatic disease. There has been concern that the cellular immune response following covid-19 infection may not be sustained. "This data is reassuring," lead study author Paul Moss, from the University of Birmingham, told a Science Media Centre briefing on 2 November. "However, it does not mean that people cannot be re-infected. We need to have much larger population studies to show that." Moss also added that the findings "can't be taken as confirmation that an 'immunity passport' would be feasible."
Major Events: 2/1 Ino-4800 Completed P2 Enrollment. 2/2 4:50P ET JK’s Ino-4800 Update at NY Academy of Sciences. 3/8 KB, TMO at 2ND ANNUAL EUROPEAN HEALTHTECH CEO FORUM
1. INOVIO Completes Enrollment in Phase 2 U.S. Trial of INO-4800 for COVID-19 DNA Vaccine; Interim Results Expected in early March, Submitted to FDA in March
2. The Quest for a COVID-19 Vaccine
Tuesday, February 2, 2021, 10:00 AM - Wednesday, February 3, 2021, 5:35 PM EST
Presented By
Microbiology and Infectious Diseases Discussion Group
The New York Academy of Sciences
Tuesday
February 02, 2021
10:15 AM
KEYNOTE ADDRESS
Speakers
Moncef Slaoui, PhD
Operation Warp Speed
Keynote Chair: Stanley Plotkin, MD
University of Pennsylvania
11:00 AM
KEYNOTE ADDRESS: The Year in Review: A Vaccinologist’s Perspective
Speakers
Anthony S. Fauci, MD
National Institute of Allergy and Infectious Diseases (NIAID), NIH
Keynote Chair: Nicholas B. Dirks, PhD
New York Academy of Sciences
SESSION III: Efficacy Studies, Part 1
Session Chairperson
Annaliesa Anderson, PhD, Pfizer
2:50 PM
Efficacy Data Updates from Moderna’s mRNA Vaccine Candidate
Speaker
Tal Zaks, MD, PhD
Moderna
3:20 PM
Efficacy Data Updates from Pfizer’s mRNA Vaccine Candidate
Speaker
Kathrin Jansen, PhD
Pfizer
3:50 PM
Break
4:00 PM
Efficacy Data Updates from Novavax’s Protein-based Vaccine Candidate
Speaker
Gregory Glenn, MD
Novavax
SESSION IV: Update Talks
Session Chairperson
Emmanuel Hanon, PhD, GlaxoSmithKline
4:30 PM
Updates from Codagenix’s Vaccine Candidate
Speaker
J. Robert Coleman, PhD, MBA
Codagenix
4:50 PM
Updates from Inovio Pharmaceutical’s DNA Vaccine Candidate
Speaker
J. Joseph Kim, MBA, PhD
Inovio Pharmaceuticals
SESSION V: Day 1 Closing Talk
Session Chairperson
Stanley Plotkin, MD, University of Pennsylvania
5:10 PM
The Role of Modern Vaccinology in Responding to New Epidemics
Speaker
John R. Mascola, MD
National Institute of Allergy and Infectious Diseases, NIH
https://www.nyas.org/events/2021/webinar-the-quest-for-a-covid-19-vaccine/
3. KB, TMO, Raghuram Selvaraju HCW speak at 2ND ANNUAL EUROPEAN HEALTHTECH CEO FORUM
FOR PARTNERING & INVESTMENT
8TH-9TH MARCH 2021 | DIGITAL CONFERENCE
HealthTech Innovation Day (Monday, 8th of March)
Digital Healthcare in the New Era of COVID-19 Panel
Digital Pharma & Drug Discovery Panel
MedTech & Device BD and Investment Panel
Revolutionising Hospital Care: New Technologies Panel
Innovation in Care Technology Panel
Innovation & Early Stage Investment Roundtable
Pandemic Response Day (Tuesday, 9th of March)
The Global Supply Chain in the Time of COVID-19 Panel
Overview of Vaccine Development & Roll Out Panel
Advanced Therapeutics Panel
Diagnostics: New Technologies Panel
Patient Care in the Time of the Pandemic Panel
Networking Days (10th - 12th of March)
Confirmed Keynote Speakers Include:
Introductory Speech by Jeffrey Cohen, Managing Director, Equity Research, Ladenburg Thalmann & Co. Inc.
Mark Stevenson, Executive Vice President & Chief Operating Officer, Thermo Fisher Scientific
Fireside Chat with Sean Marett, Chief Business Officer & Chief Commercial Officer, BioNTech SE
Confirmed Speakers Include:
Kate Broderick, Senior Vice President, Preclinical R&D, INOVIO Pharmaceuticals, Inc.
Raghuram Selvaraju, Chairman of the Board, Relief Therapeutics Holding AG and Managing Director, H.C. Wainwright & Co., LLC
https://www.sachsforum.com/2ehtf-about.html
The Quest for a COVID-19 Vaccine
Updates from Inovio Pharmaceutical’s DNA Vaccine Candidate. Time: 2/2/21 4.50pm ET (that's market AH ET)
Speaker: J. Joseph Kim, MBA, PhD, Inovio Pharmaceuticals
Stanley Plotkin, MD
University of Pennsylvania
Tuesday, February 2, 2021, 10:00 AM - Wednesday, February 3, 2021, 5:35 PM EST
Presented By
Microbiology and Infectious Diseases Discussion Group
The New York Academy of Sciences
Through a series of keynote and plenary presentations, major themes to be considered for the program include:
the clinical epidemiology of COVID-19
the virology, immunology, and genetics of SARS-CoV-2,
efficacy data updates from candidate vaccines in Phase 3 trials,
updates from Phase 1 and 2 vaccine candidates,
COVID-19 vaccines in the elderly,
outbreak predictions, and
future considerations for the development and distribution of a COVID-19 vaccine
https://www.nyas.org/events/2021/webinar-the-quest-for-a-covid-19-vaccine/?tab=description
The domestic new crown vaccine also has a secret weapon-DNA vaccine, with a shelf life of up to 5 years
January 25, 15:58
The large-scale vaccination of the new crown vaccine has been spread around the world, and the "stability" that determines the convenience of transportation and storage has become a hard indicator to test a vaccine. In my country's new coronavirus vaccine team, there is a vaccine that has a shelf life of up to 5 years at standard refrigeration temperatures (2-8°C) and can remain stable for more than 1 year at room temperature. Once put into use, it will bring great convenience to the popularization of the vaccine.
This is the new crown DNA vaccine. This vaccine was jointly developed by Ai Di Weixin (Suzhou) Biopharmaceutical Co., Ltd. (hereinafter referred to as "Ai Di Weixin") and the American biopharmaceutical company INOVIO, and is currently conducting phase 2 clinical trials simultaneously in China and the United States. Due to the high technical threshold, currently no human DNA vaccine has been successfully marketed in the world. This is also the first preventive DAN vaccine approved to enter the clinic in my country.
Dr. Liu Xiaoyan, Strategic Director of Ai Diweixin, said in an interview with The Paper (www.thepapaer.cn) recently, “This vaccine may become the first DNA vaccine in history to be approved for marketing, and it marks my country’s role in the field of nucleic acid vaccines. Reach the most advanced level in the world."
DNA vaccines and mRNA vaccines are both nucleic acid vaccines, which are called "third-generation vaccine technology" in the industry. At the end of 2020, the new crown mRNA vaccine has achieved a breakthrough from zero to one, and the development of DNA vaccines has also been closely watched by the industry.
What is the new crown DNA vaccine?
In the global competition of the new crown vaccine, my country's three inactivated vaccines have always been the leader, becoming one of the most familiar technical routes for the public. In fact, the new crown NDA vaccine also has many scientific research teams "betting". According to the latest data released by WHO on January 22, 2021, Central European Time, there are currently 64 new crown vaccine candidates in the world that have entered the clinical research phase. Among them, 9 inactivated vaccines (accounting for 14%) and DNA vaccines 8 models (accounting for 13%), in terms of quantity, the two are evenly matched.
According to data released by WHO on January 22, 2021, Central European Time, a total of 64 new crown vaccine candidates worldwide have entered the clinical research phase, including 8 DNA vaccines (DNA) and 9 inactivated vaccines (IV). WHO official website map
The new crown DNA vaccine is also one of the five technical routes deployed after the epidemic in my country, which belongs to the technical route of nucleic acid vaccines. At that time, Ai Diweixin's new crown DNA vaccine project was approved by the Ministry of Science and Technology, and was selected by the State Council for the joint prevention and control of new coronavirus pneumonia vaccine tasks, and received continuous follow-up and support from the Ministry of Science and Technology and the National Health Commission.
Liu Xiaoyan introduced that the principle of DNA vaccine is to make the DNA encoding the antigen protein into a vaccine, enter the human body and express the antigen in the body to induce the human body to produce an immune response, so that the vaccinators can obtain the corresponding immune protection ability and achieve the purpose of disease prevention.
After the new coronavirus DNA vaccine is immunized, it will help the human body to produce memory T and B cells. When it encounters the new coronavirus invasion again, it can quickly produce a large number of effector T cells and B cells, neutralize the invading virus through antibodies, and pass T cells ( Cellular Immunity) destroys viruses that have infected the cells.
Li Bin, deputy director of scientific research at the Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, introduced in an interview with The Paper that the inactivated vaccine, as a traditional classic technical route, uses an in vitro culture method to prepare antigens, and then inject viral antigen proteins into the human body. Activate the human immune response; and the DNA vaccine of the new generation of technology routes directly input genetic coding information into the human body to produce antigen proteins in the body and activate the immune response.
Li Bin said that the biggest advantage of DNA vaccines is that they can be stored for a long time at room temperature.
INOVIO issued a statement on its official website on December 24, 2020 local time, stating that INO-4800 (the new crown DNA vaccine developed by INOVIO and Ai Diweixin) can remain stable for more than 1 year at room temperature, at 37°C. It can be kept stable for more than one month. Its design shelf life is 5 years at standard refrigeration temperature (2-8°C), and it does not need to be frozen during transportation and storage.
"These are the decisive factors in the fight against the new crown and the timely distribution of vaccines around the world." The statement said.
Liu Xiaoyan introduced that the "5-year shelf life" is based on the results of long-term stability studies at room temperature for other DNA vaccine products developed by INOVIO. According to INOVIO's official website, the company has extensive experience in coronaviruses and has developed a DNA vaccine for Middle East Respiratory Syndrome (MERS) caused by related coronaviruses. The vaccine is INO-4700.
"DNA vaccines are very stable and can be stored for a long time at room temperature. They are suitable for remote areas or as a strategic reserve for vaccines. In contrast, mRNA vaccines have very high requirements for the cold chain and high transportation costs. The availability of vaccines poses challenges." Liu Xiaoyan said.
Both are nucleic acid vaccines, and the transport of mRNA vaccines is inseparable from the cold chain. In terms of the two COVID-19 vaccines currently in use in the world, Pfizer /BioNTech’s vaccine needs to be transported at -80? to -70?, while Modena’s vaccine needs to be transported at -20? .
Liu Xiaoyan said that the advantages of DNA vaccines also reflect production. He introduced that DNA vaccines are produced by E. coli fermentation, the expression system is very mature, can be quickly mass-produced, and the process is mature at low cost; while mRNA vaccines are mainly produced by synthetic methods, and large-scale synthesis is relatively difficult and requires certain Time to achieve mass production, and the cost is high.
INO-4800 is conducting clinical trials simultaneously in China and the United States
Liu Xiaoyan introduced that in July 2020, Ai Diweixin's new crown DNA vaccine was approved to enter clinical trials in China. The Phase 1 clinical trial has been successfully carried out in Shanghai Huashan Hospital. In September of the same year, the first subject was vaccinated. All 45 healthy subjects have now been vaccinated with two injections and entered the follow-up phase. In December 2020, this DNA vaccine officially entered a phase 2 clinical trial in China, which was carried out in Jiangsu Province in cooperation with the Jiangsu Provincial Center for Disease Control and Prevention.
A statement issued on the INOVIO official website on December 10, 2020 local time shows that the phase II clinical trial of INO-4800 in China has completed the first subject vaccination. This clinical trial is expected to include approximately 640 18-year-olds And above subjects.
"It is expected that in the first quarter of this year, we will be able to start Phase 3 clinical trials." Recently, Liu Xiaoyan said in an interview with The Paper.
The aforementioned INOVIO statement issued on December 10 last year stated that the Phase 2 clinical trial of INO-4800 in China and the first Phase 2/3 clinical trial conducted in the United States are independent of each other. Liu Xiaoyan introduced that Ai Diweixin and INOVIO jointly developed this new crown DNA vaccine, but each applied for and carried out clinical trials in China and the United States, so phase 1 and phase 2 clinical trials were carried out independently.
On December 23, 2020 local time, the authoritative medical journal "The Lancet" sub-issue "Clinical Medicine" ("EClincalMedicine") published the results of the Phase 1 clinical trial of INO-4800 in the United States. The paper is "New Coronary DNA Vaccine INO- The safety and immunogenicity of 4800: A preliminary report of an open-label Phase 1 clinical trial ("safety and immunogenicity of INO-4800 DNA vaccine against SARS-CoV-2: A preliminary report of an open-label, Phase 1 clinical trial").
According to the paper, INO-4800 was evaluated in two groups of participants (20 people in each group). Each group received a subcutaneous injection of 0.1 mg or 2.0 mg vaccine, and then used the CELLECTRA® electroconverter in the 0th and 4th weeks. (A medical device). Thirty-nine subjects completed two doses, and 1 subject in the 2.0 mg group discontinued trial participation before the second dose.
The test results show that INO-4800 has good safety and tolerability, and by triggering cellular or (and) humoral immune responses, it is immunogenic in 100% (38/38) of the subjects.
In particular, the research team wrote that only Grade 1 (mild) adverse events (mainly local reactions at the injection site) were recorded in the trial, which has advantages over the existing approved vaccines. For a successful new coronavirus vaccine, safety is very important, which can support the extensive research of INO-4800 in high-risk populations who are more susceptible to complications of new coronavirus infection, such as the elderly and patients with comorbidities.
Let DNA "drill" into the cell
According to a previous report by "Shanghai Science and Technology News", the signing ceremony of the cooperation agreement between the National Health Commission/Key Laboratory of Ministry of Education of Medical Molecular Virology and Ai Di Weixin to strengthen the support of new crown DNA vaccine technology was held in June 2020. At that time, the Chinese Academy of Engineering Academician Wen Yumei said that Ai Diweixin's new crown DNA vaccine has two innovations: First, when constructing DNA, the design of ODN (oligonucleotide) makes the DNA vaccine effective in both cellular and humoral immunity. ; Second, because of the application of the electroporation device, the delivery efficiency of DNA in the human body has been improved.
The electroporation device refers to the CELLECTRA® electroporation device. Liu Xiaoyan introduced that the current phase II clinical trial of INO-4800 in the Jiangsu Provincial Center for Disease Control and Prevention is to use injections and then use the CELLECTRA® electrotransmitter. The CELLECTRA® electrotransmitter is an electrical pulse meter, which is a medical device. After the DNA vaccine has been injected, the electroconverter can quickly complete the delivery of the DNA vaccine.
Liu Xiaoyan introduced that the working principle of the electroporator is to use instantaneous current to physically open the cell membrane. Some holes will appear in the cell membrane momentarily, allowing DNA plasmids to enter the cell through the holes, thereby greatly improving the delivery efficiency of DNA vaccines. When the instantaneous current ends, the hole in the cell membrane is closed.
"Currently DNA vaccine-related clinical trials generally use electroporation devices, which are more common. In addition to preventive vaccine products, there are also therapeutic varieties, including cancer vaccines, which will use electroporation devices." Liu Xiaoyan introduced.
Regarding the introduction of electro-transfer technology, the article "Research Progress in DNA Vaccine Against Novel Coronavirus" published in the "Chinese Journal of New Drugs" on November 15, 2020 has a detailed introduction. The article stated that in the early stages of DNA vaccine development, after intramuscular and subcutaneous injection, the plasmid DNA is captured by muscle cells and monocytes for antigen expression. However, naked DNA is easily degraded by deoxyribonuclease (DNase) and lysosome, making it difficult to enter cells, resulting in very limited expression levels of these DNA vaccines, resulting in low immunogenicity.
In recent years, some strategies have emerged to improve the immunogenicity of DNA vaccines, including improvements in delivery methods, and the application of electrical pulses (electroporation) is one of them.
The article stated that the delivery of DNA vaccines through an electric pulse meter can increase the level of DNA vaccines entering animal cells, leading to more antigen expression. The delivery experiment with the introduction of electric pulses proved that the level of DNA vaccines entering muscle cells increased significantly and produced thousands of times the effect of gene expression. At present, the electric pulse meter has been widely used in various clinical trials, which not only greatly improves the efficiency of DNA vaccine immune activation, but also proves that it has little impact on the human body and no serious adverse events have occurred.
Liu Xiaoyan said that DNA vaccines are generally delivered by physical means (electrotransformation technology), and there is no potential safety risk caused by the introduction of new molecules such as liposomes, while mRNA vaccines are generally delivered through liposome encapsulation. Therefore, modification and Encapsulation technology and the toxicity of liposomes are problems that need to be solved by mRNA vaccines.
Build China's largest DNA vaccine and plasmid production base
The article "Research Progress in DNA Vaccines Against New Coronavirus" introduced that nucleic acid vaccines have been called "third-generation vaccine technology" in the industry after traditional attenuated vaccines, inactivated vaccines and genetic engineering subunit vaccines, including DNA vaccines and mRNA vaccine.
DNA vaccine originated in the 1990s. In the past 20 years, scientists have conducted a large number of DNA vaccine studies on animals, including fish, mice, chickens, cats, dogs, pigs and monkeys. So far, a total of 5 animal DNA vaccine products have been on the market, including DNA vaccines to prevent salmon from being infected with infectious hematopoietic necrosis virus, DNA vaccines to treat dog melanoma, and to reduce the morbidity and mortality of sows during delivery. DNA products and avian influenza DNA vaccine approved by the Ministry of Agriculture of China in 2018. But so far, there is still no human DNA vaccine product on the market.
In an interview with The Paper, Liu Xiaoyan said that before the new crown DNA vaccine, my country had not yet been approved for a preventive DNA vaccine into the clinic. "This vaccine may become the first DNA vaccine approved for marketing in history, and it marks that my country has reached the world's most advanced level in the field of nucleic acid vaccines." Liu Xiaoyan said.
According to previous reports from Shanghai Science and Technology News, the domestic phase I clinical study of the vaccine was carried out at Huashan Hospital. Zhang Wenhong, director of the Department of Infectious Diseases at Huashan Hospital, was one of the investigators who applied for the clinical trial. In Zhang Wenhong's view, this cooperation is meaningful and not only limited to the development and production of the new crown vaccine, because after the new crown epidemic, there may also be other infectious disease challenges. “In China, we must not only carry out vaccine research, but also establish a platform for vaccine research and development. If we encounter epidemics caused by similar viruses in the future, we can respond quickly. After the new crown nucleic acid vaccine enters clinical trials, its safety in humans The sex and effectiveness data will also lay a solid foundation for the future development of nucleic acid vaccines."
In Liu Xiaoyan's view, the establishment of a nucleic acid vaccine technology platform is of great significance. "Especially in response to emergencies of public health or biosafety, the nucleic acid vaccine technology platform can effectively provide rapid response technical support and guarantees. Once the nucleic acid vaccine technology platform is determined, the production process and quality control system can be universal and reproducible. The application does not change due to the genetic changes of the antigen. Therefore, the degree of standardization of the nucleic acid vaccine platform technology CMC is higher, which can reduce a lot of preclinical work and is suitable for the rapid development of new products."
While carrying out clinical research, the capacity building of the new crown DNA vaccine is also advancing simultaneously.
Liu Xiaoyan introduced that Ai Di Weixin is building China's largest DNA vaccine and plasmid production base in the Suzhou Biomedical Industrial Park. The new crown DNA vaccine industrialization project is being constructed in stages. The first stage is designed to produce 20 million doses per year, and the second stage The designed production capacity is 100 million doses per year. As of January 2021, the first phase of construction is nearing completion.
https://jvkkhloxjzty53ub3e565667pe-adwhj77lcyoafdy-finance-sina-cn.translate.goog/2021-01-25/detail-ikftssap0625441.d.html?from=wap
Citron to stop publishing short-selling research, Andrew Left says
'When we started Citron, it was to be against the establishment, but now we've actually become the establishment'
Jan 29, 2021
Short-seller Andrew Left, whose company Citron was one of the hedge funds to spark this week’s battle with small-time traders over GameStop Corp, said in a YouTube video on Friday that his company would no longer publish short-selling research.
The latest twist in a saga that has sent shock waves through Wall Street as amateur investors pile into heavily-shorted stocks like GameStop and AMC Entertainment Holdings Inc., the move is a major change of course for one of world’s best known short-sellers.
Left, the author of dozens of investigative reports on S&P 500 over the past decade, is credited as helping pioneer the tactic of betting against a stock by publishing research that encouraged others to follow his lead and profiting when they do.
“As of today, Citron Research will no longer be publishing what can be considered as short-selling reports,” Left said in the video. “The Citron narrative is going to change and have a pivot.”
Short sellers typically bet against companies that they believe have outdated business models or are overvalued.
Hedge funds are known for the tactic but only a handful of firms – including Citron, Jim Chanos’ Kynikos Associates, Carson Block’s Muddy Waters Research, and Ben Axler’s Spruce Point Capital Management – specialize in it.
Left’s retreat, which follows his abandonment earlier this week of the bet against GameStop, comes as funds and other investors who have shorted U.S. stocks face the prospect of tens of billions of losses on the trades.
Melvin Capital, a US$13-billion hedge fund, on Monday received a financial lifeline of nearly US$3-billion from Citadel and Point72 Asset Management after being crippled by short bets that went the other way.
Pulling the plug
Left had said earlier this month that he had shorted GameStop with its share price at around US$40, expecting it to halve in value.
On Friday, he reiterated his conviction that GameStop was a dying business and its stock price would fall sharply in the future.
“If you choose to buy GameStop here, it’s caveat emptor. You know what we think about their business model. It’s on you,” Left said.
Citron’s most famous short positions include those against companies including Valeant Pharmaceuticals International Inc and electric vehicle maker Nio Inc, which led to shares of those companies collapsing.
“When we started Citron, it was to be against the establishment, but now we’ve actually become the establishment,” Left said on Friday.
GameStop shares jump 68% on Friday, bringing gains for the week to 400%.
Shares of GameStop, AMC and other heavily shorted stocks spiked on Friday, building on an overnight rally in extended trading, after Robinhood said it would resume limited trading of previously restricted securities.
Individual investors are creating short squeezes by piling into names that hedge funds are betting against, forcing the funds to rush to cover their losses. This typically pushes shares even higher. Retail investors are promoting their activity on the WallStreetBets Reddit board, which has more than 3 million members. Some view it as small investors pushing back against the Wall Street establishment.
SVB Analyst Leerink “T cells could still mount a response against the mutant COVID strains, because they may respond to different types of protein fragments than the antibodies recognize”
Pfizer and Moderna haven't proven their COVID-19 vaccines shield against new variants: analysts
by Arlene Weintraub | Jan 28, 2021 10:52am
Just as the U.S. government is starting to ramp up purchases of Pfizer’s and Moderna’s mRNA vaccines to prevent COVID-19, a troubling question is emerging in the scientific community: Can these shots protect people against aggressive new variants racing through the U.K., South Africa and Brazil?
Several analysts have scoured the medical literature and interviewed infectious disease experts in an effort to answer that question. Their conclusion? There is no clear answer. At least not yet.
When it comes to SARS-CoV-2, the virus at the heart of the pandemic, “we are in a state of ignorance with incomplete data,” said SVB Leerink analyst Geoffrey Porges in a note to clients Wednesday. He reached that conclusion after interviewing an infectious disease specialist who is also an official with the FDA, he said.
Moderna analyzed the South African variant and found its vaccine produced sixfold fewer neutralizing antibodies against that strain than it did against the original virus. Then Pfizer followed with an analysis suggesting its vaccine was only slightly less effective against the South African strain.
Problem is, Pfizer’s analysis did not include all the mutations found in the South African variant of SARS-CoV-2, said Evercore ISI analyst Umer Raffat in a Wednesday note. In fact, it didn’t include a certain mutation that’s known to be problematic, he said. Therefore, because “the simultaneous co-mutations is where the neutralization activity starts to dip,” Pfizer’s analysis may not be entirely comprehensive, he said.
In a separate note from SVB Leerink on Thursday, analysts pointed out vaccine makers have been testing their shots against new variants using assays that “are not validated to predict vaccine efficacy.” Typically, they’re isolating antibodies from people who received the vaccines and then testing them against “pseudoviruses” that have a single mutation from a new variant of the coronavirus.
Furthermore, it’s possible the immune system’s T cells could still mount a response against the mutant COVID strains, because they may respond to different types of protein fragments than the antibodies recognize, the analysts said. But this phenomenon has not been fully studied, therefore it’s impossible to quantify the contribution of T cells to the immune response, they wrote.
Moderna isn’t taking any chances with the emerging coronavirus variants, though. It has moved a booster vaccine that addresses the South African variant into preclinical studies and a phase 1 human trial, the company announced Monday. “As we seek to defeat the COVID-19 virus, which has created a worldwide pandemic, we believe it is imperative to be proactive as the virus evolves,” said CEO Stéphane Bancel, in a statement.
Tuesday, Pfizer and its mRNA vaccine partner BioNTech followed suit, confirming they’re also working on booster shots that shield against the new COVID variants.
One advantage of the mRNA technology behind the Moderna and Pfizer products is that it allows for new vaccine constructs to be rolled out quickly, SVB Leerink’s Porges said. The FDA official he interviewed “confirmed that the development of ‘next generation’ vaccines containing the novel variant sequences could be very fast using the established platforms, potentially requiring only a ‘few hundred’ subjects that could be enrolled, vaccinated, and studied ‘in a matter of weeks.’”
The same also apples to DNA vaccine Ino-4800.
BlackRock, Inc. Signature: Spencer Fleming 1(a) Name of issuer: INOVIO PHARMACEUTICALS INC
Item 1(b) Address of issuer's principal executive offices:
6769 MESA RIDGE RD.
SAN DIEGO CA 92121
2(b) Address or principal business office or, if none, residence:
BlackRock, Inc.
55 East 52nd Street
New York, NY 10055
Dated: January 29, 2021
BlackRock, Inc.
Signature: Spencer Fleming
1/29/21 BLACKROCK, INC. files Schedule 13G owning 8.4% of Ino shares, 14,242,941, could take Ino private at high price.
(5) Sole voting power
13961421
(9) Aggregate amount beneficially owned by each reporting person
14242941
(11) Percent of class represented by amount in Row 9
8.4%
BLACKROCK, INC.
By:_ /s/ Daniel Waltcher
Name: Daniel Waltcher
Title: Deputy General Counsel
Subsidiary
BlackRock Life Limited
BlackRock Advisors, LLC
BlackRock (Netherlands) B.V.
BlackRock Institutional Trust Company, National Association
BlackRock Asset Management Ireland Limited
BlackRock Financial Management, Inc.
BlackRock Japan Co., Ltd.
BlackRock Asset Management Schweiz AG
BlackRock Investment Management, LLC
BlackRock Investment Management (UK) Limited
BlackRock Asset Management Canada Limited
BlackRock Investment Management (Australia) Limited
BlackRock Fund Advisors
BlackRock Fund Managers Ltd
http://d18rn0p25nwr6d.cloudfront.net/CIK-0001055726/e244ca53-751a-4532-b600-392c9ceaecb9.pdf
B.1.1.7 variant Requires booster doses playing into Ino-4800 strength
Hours before President Biden’s Covid-19 team gave their first virtual press conference, the famed AIDS researcher David Ho delivered concerning news in a new pre-print: SARS-CoV-2 B.1.351, the variant that emerged in South Africa, is “markedly more resistant” to antibodies from convalescent plasma and vaccinated individuals.
The news for several monoclonal antibodies, including Eli Lilly’s bamlanivimab, was even worse: Their ability to neutralize was “completely or markedly abolished,” Ho wrote. Lilly’s antibody cocktail, which was just shown to dramatically reduce the risk of hospitalizations or death, also became far less potent.
The B1.351 variant has yet to be seen in the US, new CDC director Rochelle Walensky assured reporters, but the variants nonetheless took up a substantial portion of the first Covid-19 briefing, as Walensky and NIAID director Anthony Fauci outlined steps the US would take as they became more common in the country and as the virus continues to mutate, potentially in ways that make them yet more resistant to vaccines and antibodies.
The B.1.1.7 variant, now dominant in the UK and growing in the US, hasn’t been able to significantly elide vaccines or monoclonal antibodies, Fauci said. There’s growing evidence, though, that the variant common in South Africa can avoid monoclonals and some antibodies produced by vaccines.
Because the Pfizer and Moderna vaccines are so effective, Fauci said, potency can drop considerably without impacting efficacy, and there are no data to suggest the vaccine isn’t still protective.
“However,” he said, “given that as a fact now, we have to be concerned about what further evolution of this might be.”
So far, the only tests for whether vaccines and monoclonal antibodies can neutralize new variants have been in vitro studies — test tube experiments where the antibodies are mixed with a fake version of SARS-CoV-2 the experimenter checks to see whether the virus still managed to infect cells. Those experiments, conducted both by companies and in academic labs, have been encouraging for B.1.1.7 and discouraging for B.1.351.
The new Ho paper, for example, conducted in collaboration with the NIH and Regeneron, showed 10 out of 12 antibodies were equally effective against B.1.1.7 and two were only slightly less effective, while vaccine efficacy fell 2-fold. The B.1.351 variant, though, almost entirely avoided five of the monoclonal antibodies, while vaccine efficacy fell 6.5-fold for Pfizer and 8.6-fold for Moderna.
Soon, though, the US is likely to get data on how the vaccine works against the different variants in the real world, Fauci said. J&J conducted their pivotal vaccine trial around the world, including in South Africa and Brazil, where another variant, called P.1, has spread. Their results should come “within the next few days,” Fauci said.
“What we will see was the relative efficacy against the wild type virus that is predominantly in the US, as well as the South African isolate,” Fauci said. It “will inform us of where we would go, if the eventuation occurs that we do have that particular lineage seed itself in the United States.”
In the meantime, vaccine and antibody developers have been preparing for that potential. Moderna developed a vaccine designed specifically for B.1.351 and has said they will start Phase I trials using both the new vaccine and the original as a booster shot. Pfizer and Novavax said they are also drawing up contingency plans.
The Ho paper pointed antibody developers, who are more acutely threatened by a mutating virus than vaccine companies, to a potential solution. Although Eli Lilly’s main antibody did little against the new variant, Regeneron’s combo still successfully neutralized it, pointing to the potential importance of combination strategies.
Still, a combo isn’t necessarily a panacea, as shown by the low potency Ho found for Lilly’s cocktail. The Indianapolis-based Big Pharma announced this morning, though, that they began experimentally dosing patients with a combination of bamlanivimab and an antibody Vir and GSK are co-developing. In a statement, GSK noted that the two antibodies bind to different epitopes, or sub-units, of the virus.
‘I was lucky to find this vaccine anywhere’. Stanley Plotkin, legendary vaccinologist, on the historic development and chaotic distribution of covid-19 vaccines
By Eli Saslow
JANUARY 27, 2021
I’ve been so focused on helping to develop these vaccines that I barely thought about the mechanics of getting it myself until this month. How can our process be this complicated? I’ve been calling around now for the last several weeks. I could not find out where, or when, or how to receive a vaccine. I didn’t get anywhere.
I’m 88 years old. I’m in the priority group, and I qualify by all the Phase One recommendations. That should be enough. I don’t want to jump ahead of anyone in the line. I don’t want to call somebody up on the phone and say: “You know, I actually consulted on this vaccination process. I wrote the textbook on vaccines.”
If I’m not able to get in through the normal channels, that means a lot of people like me are not getting in, and that’s a big problem. We shouldn’t be experiencing this level of chaos in a developed country at a time like this. I live in a suburb of Doylestown, which is the county seat here in Bucks County, so it’s not like I’m way out in the hinterlands. I did research online and registered for all sorts of things with the state and county, and I never heard back. I called and called and couldn’t find a way to get vaccinated within 20 miles of my house. My wife got frustrated on my behalf and started searching outside the area, and just by chance a few days ago she found a hospital in a different town that had openings left for the Moderna vaccine. I’ve barely left home to get the newspaper, but I was lucky to find this vaccine anywhere. I realize a big part of the problem is the lack of supply, but millions of people are being left on their own to navigate this disorganized mess. It’s a free-for-all. What kind of system is that?
The whole experience of this pandemic has taken us through the emotional extremes. There’s my frustration with our national response, which has not been proportional to the threat of this virus. But I also try to focus my mind on the encouraging moments, and we’ve had many. Our vaccine development has been remarkable. There are many reasons for doom and gloom, but the science is sustaining.
Let’s not exaggerate my own role in all of this. I don’t have a laboratory anymore, so all I can do is consult. I’ve been offering my advice to the World Health Organization and the Gates Foundation. I serve on a board for Moderna and communicate with Oxford, Sanofi and Inovio. I helped create the Coalition for Epidemic Preparedness Innovations, and it’s supporting the development of about eight vaccines, but I can’t take credit for what’s come down the line. I’ve been cheering from the sidelines and shouting out my suggestions. I’ve been incredibly busy without ever leaving my house.
What I’ve been focused on lately is advocating within these organizations for a change in our vaccination strategy, so we get one dose to as many people as possible over the next few months. I’ve looked over the data, and it suggests that you have pretty good immune protection starting 12 days after the first dose. Obviously, you need a second dose to get long-term protection, but the immune system stays primed for the second dose for at least six months. I’m suggesting we wait on the second dose for up to 12 weeks until our supply improves. Otherwise a lot more people are going to be calling around and striking out like I’ve been doing. It’s a controversial approach, but an extraordinary disease requires extraordinary solutions.
Now, will anybody listen to me? I don’t know. One of the advantages of being older and somewhat respected is that people are polite about soliciting my advice, even if they don’t always take it. They value my experience. I cut my teeth on polio and anthrax in the 1950s. I developed the rubella vaccine that’s now in standard use throughout the world, and I’ve worked on vaccines for rotavirus, rabies, Lyme disease, and cytomegalovirus. When I first started, we only had two ways to develop a vaccine, and now we have many more methods that show incredible promise. More than 100 vaccines are being developed against this virus — all in record time. Science is cumulative. It builds steadily toward progress, and that’s been my answer to despair during this last year. I can look back over my life and see a degree of advancement that’s staggering.
We can say with justification that vaccines have changed the world, and that gives me hope that they can do so again. I had contracted three diseases by the time I was 10 years old that are now prevented by vaccine: pertussis, pneumococcal pneumonia and severe influenza. At that time, only a handful of vaccines were given to children. Now, at least 16 are on the routine schedule. Parents can expect their children to grow up, and that’s a relatively new thing. It shouldn’t be taken for granted. But because people now have the great luxury of forgetting about these diseases, we are starting to run into all kinds of strange conspiracy theories about vaccines. Some people revert back to the Dark Ages of mysticism and pseudoscience. The White House had that guy [Scott] Atlas. I mean, my God! The minimizing, the skepticism about masks — you couldn’t have made it up. Then there are people like Andrew Wakefield or Robert Kennedy, who have influence and use it to spout nonsense about vaccines, and that’s dangerous.
If I were president, every child in the country would be required to take a course in statistics. Opinions don’t count for all that much. Facts count, and we have a lot of data about the safety of vaccines. Nobody can say vaccines are 100 percent safe. There’s nothing that’s 100 percent safe. That’s ridiculous. But there is a system in place, called the National Vaccine Injury Compensation Program, to financially compensate people for vaccine reactions, in which the evidence is presented to a panel that weighs the facts and then decides. It works out to be about one compensable reaction per every one million doses of any particular vaccine. So then you have to ask yourself: What is the risk of the disease at the moment? This virus is replicating. It is constantly making more of itself, and during that process there are always variations and mutations that occur. I don’t think there is any doubt that the risk of this disease is a hell of a lot bigger. Any reasonable person should accept vaccines on the basis of logic. Unfortunately, logic does not predominate around the world.
Organisms, viruses — they are not going away. They will continue to cause epidemics. This virus will likely persist in the form of sporadic cases and occasional outbreaks no matter how hard we try. What we may be looking to is an influenza-like situation, with a virus that mutates over time, and we will have to tweak the vaccine sporadically to meet those changes. I hope I’m wrong, but I’m not optimistic this virus will entirely disappear. We live in a world where you can wake up in Kampala and go to bed in New York. The spread of viruses through human agency is more likely now than ever.
It’s not an exaggeration to say our future depends on finding solutions. That’s why I wanted to work in a laboratory ever since I was about 15. It is tedious and uncertain work, but it has aspects of an almost religious experience. You are that explorer in unknown territory. I think back to a Tennyson poem, “Ulysses,” which I quoted long ago in my college yearbook: “To follow knowledge like a sinking star, beyond the outmost bounds of human thought.”
Say all you want about the horrors of this last year, but we have reached those outmost bounds. We have accomplished more than I would have imagined possible, and it’s been a global effort. It’s astounding. It’s thrilling. I was about to say it’s miraculous, but that’s not right. I don’t believe in miracles. It might sound a little fancy, but I believe in science. I believe in our capacity to endure and overcome.
04:54 PM 1/28/21 day 1 after injection. No symptoms from 4800. A little redness. Praying I got the actual vaccine and not the placebo. Hang in their guys. By snarrjj88
https://stocktwits.com/snarrjj88/message/279721008
That’s the last 1st dose for P2. Expect Ino to issue a press release Mon 2/1/21. Ino’s partner in China, Advaccine completed last 2nd dose. Two weeks later they will read out 2/11 for dose selection. 2/25 they will submit to authority to get OK to start P3 early March. Cellectra 2000 had CE Mark certified by Europe. It’s accepted everywhere in the world. FDA must be nut to require more data on it.
$37M Helps IU, Ino Develop Even Better DMAb Antibodies for COVID-19. Pallesen says the consortium, which includes AZN, Inovio, the Wistar Institute, and the University of Pennsylvania, is well positioned to fast track its discoveries to the bedside.
Thursday, January 28th 2021, 8:59 AM EST
BLOOMINGTON - The world is growing increasingly impatient with the pandemic, aching to fight it faster. A $37.6 million grant is powering a newly-formed consortium tasked with developing DNA-encoded antibodies, which can kill a COVID-19 infection faster than antibody treatments that don’t have the power of DNA. Adding even more speed to this strategy, the grant supports a two-year timeframe to reach Phase 2 clinical trials. “It’s incredibly fast,” says the Indiana University researcher tapped to play a role.
Assistant Professor of Molecular and Cellular Biochemistry Dr. Jesper Pallesen leads an IU lab with expertise in providing very detailed 3D structures of DNA-encoded antibodies and how they interact with SARS-CoV-2. The lab is part of the team formed by the $37 million grant from the Defense Advanced Research Projects Agency.
“Antibodies are the principle protein that your immune system produces in response to disease,” says Pallesen. “When there’s a pathogen in your body, eventually, your immune response will generate antibodies specific for that pathogen.”
The key word is “eventually.” The process is long for the immune system to recognize a foreign invader and build the antibodies to kill it. DNA is the difference-maker for developing a fast-acting treatment for patients fighting COVID-19; it puts the process in fast-forward.
All proteins—and in this case, antibodies—are encoded by DNA. Rather than waiting for the body to build the DNA that will power these COVID-19 fighting antibodies, Pallesen’s method provides the DNA.
“It takes a while for your immune system to arrive at a good recipe for good antibodies. We are speeding up the process for your body to produce really good antibodies by providing the recipe to do so, instead of asking your cells to find the recipe themselves,” says Pallesen. “Once we identify antibodies that are really good against a particular pathogen—SARS-CoV-2, for example—then we can produce DNA [in the lab] that specifically instructs a cell to create these antibodies that are already really good.”
Beyond speed, another major advantage of DNA-encoded antibodies is that the human body does most of the heavy lifting for “mass production.”
“Because [DNA-encoded antibodies] work instantly, you get what we call bioamplification. If we administer to a patient a little of the DNA that contains the recipe for an antibody, from each copy of DNA I administer, the patient’s body will produce lots and lots and lots of antibody copies,” says Pallesen. “That is very smart for manufacturing. We can get away with a given quantity of DNA we manufacture; we can treat many more patients than if we produce this at the protein level.”
Pallesen says, beyond the work that this grant is supporting, the DNA platform is also “incredibly important” to develop for vaccine purposes. Bioamplification is, again, a game-changer. DNA platforms could be used to encode a pathogenic protein, and when administered to a human being, it would elicit a greater vaccine response—and immediately, rather than weeks. Because the body is taking over the reproduction, DNA vaccines wouldn’t be at the mercy of manufacturing capacity, unlike today’s COVID-19 vaccines.
Perhaps even more important, says Pallesen, is that DNA vaccine platforms are very stable, even potentially at room temperature, which means “they’re easy to get to all corners of the world.” And in the U.S., cold chain storage complexities that are impacting the rollout of COVID-19 vaccines, for example, would be eliminated.
While the grant is supporting the war against COVID-19, Pallesen believes progress made with the coronavirus could inform broader efforts as well.
“I’m very excited to bring DNA-based platforms—for both therapeutics and vaccines—out of labs and clinical trials and to the bedside,” says Pallesen. “With this platform, we can service parts of the world that are currently not very easy to serve. Everyone deserves good treatment everywhere in the world, and this is a large step toward accomplishing that goal.”
Pallesen says DNA-based treatments—and on a broader scale, DNA vaccines—wouldn’t need to be kept cold because DNA is a very stable molecule.
https://www.insideindianabusiness.com/story/43251904/dollar37m-helps-iu-develop-even-better-antibodies-for-covid19
AZN supply battle erupts in Europe, Germany deters use of the Covid jab for over-65s
PUBLISHED THU, JAN 28 20215:52 AM EST
The EU has told drugmaker AstraZeneca divert supplies of its coronavirus vaccine from the U.K. to mainland Europe, as a battle rages over supplies to the bloc.
Talks to try to resolve the confrontation over supplies continued on Wednesday.
Doubts have been raised in Germany over the efficacy of the vaccine in the over-65s and on Thursday, Germany’s vaccine committee said it was recommending that the AstraZeneca vaccine should only be offered to people aged between 18-64.
This, it said, was because there was not enough data to assess the efficacy in people aged over 65.
Elderly trial participants were admitted later to phase three clinical trials of the AstraZeneca vaccine, which took place in the U.K. and Brazil, and earlier on in South Africa, and so there is less available data on the efficacy of the shot in the over-65s.
Germany’s position casts doubt on the approval of the AstraZeneca vaccine at a time when a full-blown furor has erupted between the drugmaker and the EU over supplies of the jab. The EU demanded on Wednesday that the pharmaceutical giant fulfil its agreement to supply it with millions of coronavirus vaccines, by whatever means necessary.
In a press briefing, Kyriakides said there was “no hierarchy” in the production plants named in its advance purchase agreement with AstraZeneca, and no stipulation on which ones would or wouldn’t supply the EU.
“In the contract there are four factories listed but it does not differentiate between the U.K. and Europe. The U.K. factories are part of our advance purchase agreement and this is why they have to deliver,” she said. There was no clause in the contract stating that the drugmaker would prioritize the U.K., she added.
The British-Swedish company’s CEO Pascal Soriot stoked tensions further on Tuesday when he said in an interview with Italy’s La Repubblica newspaper that its agreement with the EU was a “best effort” one and not a “contractual commitment.”
The EU hit back, demanding that the drugmaker present detailed plans over its delivery schedule. One official explicitly asked AstraZeneca to divert doses made in the U.K. to the EU, although the company did not respond to this issue, according to a Reuters report.
In the Tuesday interview Soriot said: “The U.K. government said the supply coming out of the U.K. supply chain would go to the U.K. first. Basically, that’s how it is. In the EU agreement it is mentioned that the manufacturing sites in the U.K. were an option for Europe, but only later.”
1/25 Advaccine starts INO-4800 P3 1Q21 in Huge China market. Ai Di Weixin’s strategic director, Dr. Xiaoyan Liu, said in an interview with reporters recently, “This vaccine may become the first DNA vaccine approved for marketing in history."
"It is expected that in the first quarter of this year, we will be able to start phase 3 clinical trials."
The phase 2 clinical trials of INO-4800 in China and the first phase 2/3 clinical trials in the United States are independent of each other. in China and the United States, so phase 1 and phase 2 clinical trials were carried out independently.
Ai Di Weixin is building China’s largest DNA vaccine and plasmid production base in the Suzhou Biomedical Industrial Park. The covid-19 vaccine industrialization project is being constructed in phases. The first phase is designed to produce 20 million doses per year, and 2nd phase is designed to produce 100 million doses/year, as of Jan21, the first phase of construction is nearing completion.