Inovio Pharmaceuticals Inc (INO)

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AZD7442 Twin: Monoclonal antibodies based on INOVIO’s DNA-encoded monoclonal antibodies (dMAb®s) technology.

Status: INOVIO said December 15 that scientists from the company, The Wistar Institute, AstraZeneca, the University of Pennsylvania, and Indiana University received a $37.6 million grant from the U.S. Defense Advanced Research Projects Agency (DARPA), to use INOVIO’s dMAb® technology to develop anti-SARS-CoV-2-specific dMAbs that could function as both a therapeutic and preventive treatment for COVID-19.

Under DARPA’s two-year grant, INOVIO and Wistar teams will construct COVID-19 dMAb candidates designed to mirror AstraZeneca’s traditional recombinant monoclonal antibody candidates now being tested in clinical trials to treat COVID-19, such as AZD7442. Through dMAb technology, INOVIO said, it can encode the DNA sequence for a specific monoclonal antibody in a DNA plasmid and deliver the plasmid directly into cells of the body using the company’s proprietary CELLECTRA® smart device. The resulting DNA medicine is designed to serve as a genetic blueprint that instruct the patient’s body to build its own highly specific antibodies in vivo.

According to INOVIO, dMAb candidates can be quickly developed and produced in vivo, offering a cost-effective and scalable therapeutic and preventive option for treatment of SARS-CoV-2 virus infection. INOVIO plans to advance the dMAb candidates into preclinical studies and then into rigorous, first-in-human clinical trials within one year of funding.

https://www.genengnews.com/covid-19-candidates/inovio-pharmaceuticals-and-astrazeneca-dmabs/
https://www.genengnews.com/covid-19-candidates/astrazeneca-azd7442/

Type: Long-acting antibody (LAAB) combination therapy for preventing and treating COVID-19, consisting of two monoclonal antibodies derived from convalescent patients with SARS-CoV-2 infection, AZD8895 and AZD1061. Both were discovered at Vanderbilt University Medical Center (VUMC)’s Vanderbilt Vaccine Center. The coronavirus-neutralizing antibodies were developed through the company’s program to use the Defense Advances Research Project Agency’s Pandemic Prevention Platform (P3).

2021 Status: Mixed Phase III Results—AstraZeneca acknowledged June 15 that its Phase III STORM CHASER trial (NCT04625972) did not meet the primary endpoint of post-exposure prevention of symptomatic COVID-19 with AZD7442 compared to placebo. While AZD7442 reduced the risk of developing symptomatic COVID-19 by 33% compared to placebo, the difference was not deemed statistically significant.

However, in a pre-planned analysis of SARS-CoV-2 PCR positive (detectable virus) and PCR negative (no detectable virus) participants, AZD7442 was shown to reduce the risk of developing symptomatic COVID-19 by 73% compared with placebo in participants who were PCR negative at time of dosing. A post-hoc analysis showed that in participants who were PCR negative at baseline, AZD7442 reduced the risk of developing symptomatic COVID-19 by 92% versus placebo more than seven days following dosing, and by 51% up to seven days following dosing.

“We are encouraged by the protection seen in the PCR negative participants following treatment with AZD7442,” stated Mene Pangalos, AstraZeneca Executive Vice President, BioPharmaceuticals R&D. He said the company will await results from its Phase III PROVENT pre-exposure prevention trial (NCT04625725) and Phase III TACKLE treatment trial (NCT04723394) to understand the potential role of AZD7442 in protecting against COVID-19.

STORM CHASER included 1,121 participants randomized 2:1 AZD7442 to placebo, with 23 cases of symptomatic COVID-19 accrued in the AZD7442 arm (23/749) and 17 cases accrued in the placebo arm (17/372), AstraZeneca said.

The U.S. Army Contracting Command on March 30 reserved a minimum of 100,000 doses of AZD7442 through a contract modification valuled at $204.88 million, to be funded through its fiscal 2021 research, development, test and evaluation funds. The doses will be produced in Wilmington, DE, with an estimated completion date of December 31.

AstraZeneca said March 16 that it modified an existing agreement with the U.S. government to supply up to 500,000 additional doses of AZD7442. The agreement with the departments of Health and Human Services and Defense builds on an October 2020 agreement to support late-stage development of AZD7442 and the supply of an initial 100,000 doses of AZD7442, including the option to acquire additional doses in 2021. The company also has a separate agreement to supply the Defense Department with 100,000 doses, bringing potential U.S. supplies of AZD7442 to 700,000 this year.

The NIH and its National Institute of Allergy and Infectious Diseases (NIAID) said February 8 that it was evaluating AZD7442 in the international randomized, controlled Phase III ACTIV-3 trial (NCT04501978), designed to assess the safety and efficacy of AZD7442.

ACTIV-3 is part of the NIH Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) public-private partnership, designed to develop a coordinated research strategy for prioritizing and accelerating development of the most promising treatments and vaccines. ACTIV-3 is a master trial through which NIAID is conducting multiple different trials of experimental therapeutics simultaneously. In addition to AZD7442, ACTIV-3 includes sub-studies of VIR-7831, a Vir Biotechnology/GlaxoSmithKline partnered monoclonal antibody; and of the combination of BRII-196 and BRII-198, two neutralizing monoclonal antibodies manufactured by Brii Biosciences.

If outcomes assessed at five days, after approximately 150 volunteers have received AZD7442, indicate that AZD7442 is likely to be both safe and effective, enrollment in the trial will be expanded, NIAID said, to an additional 700 participants, some of whom may have more severe cases of COVID-19. ACTIV-3’s primary endpoint is sustained recovery as defined by patients being discharged from the hospital and living at home for 14 consecutive days.

2020 Status: AstraZeneca on October 9 was awarded $486 million toward two Phase III trials and related development activities related to AZD7442, including a large-scale manufacturing demonstration project and supply of doses in the U.S. The company estimated that 100,000 doses of AZD 7442 could be available from the project for high-risk patients unable to benefit from a vaccine by December 2020.

One Phase III trial will assess the safety and efficacy of the antibody combination to prevent infection for up to 12 months in approximately 5,000 volunteers. An additional Phase III study will evaluate if AZD7442 can help prevent infection in people who have come in contact with someone with COVID-19 in a post-exposure prophylaxis setting. That study will enroll approximately 1,100 volunteers.

AstraZeneca’s Warp Speed funding comes from the Biomedical Advanced Research and Development Authority (BARDA), and the Department of Defense Joint Program Executive Office for Chemical, Biological, Radiological and Nuclear Defense and Army Contracting Command.