As Pfizer Inc. and Biontech SE start their massive phase II/III safety and efficacy trial evaluating a single nucleoside-modified messenger RNA candidate from their BNT-162-based vaccine program against SARS-CoV-2, smaller, privately held Codagenix Inc. plans a different approach.

Farmingdale, N.Y.-based Codagenix will collaborate with Open Orphan plc, a specialist contract research organization pharmaceutical services company, to conduct a phase I study of a vaccine using a human challenge model, which involves deliberately infecting healthy volunteers.

The collaborative study of Codavax-COVID, a codon deoptimized SARS-CoV-2 single-dose, intranasal candidate, will include a second dose as a surrogate viral challenge on day 28.

The trial is expected to start this fall, with initial data expected by year-end from the study of the live-attenuated vaccine that replicates slowly yet contains all SARS-CoV-2 proteins.

“Based on our animal data, we expect this vaccine to be effective with a single dose, but will also evaluate a repeat dose to assess potential for boosting and as a model for protection from wild-type challenge,” said Sybil Tasker, Codagenix’s chief medical officer.

Codagenix is a synthetic biology company using software to create computer algorithms for recoding virus genomes to build live-attenuated vaccines or viruses to prevent viral infections or treat solid tumors by inducing an immune response to all viral antigens. The technology helps engineer vaccine candidates, the company said, that are structurally identical to naturally circulating SARS-CoV-2 at the amino acid level yet cannot efficiently replicate in vaccine recipients. The approach is designed to stimulate an immune response similar to the wild-type virus response without clinical illness or further transmission.

The process of generating vaccine candidates for animal studies takes weeks, the company said, because they are 100% identical to the circulating viral strain at the amino acid level.

The human challenge model

An attenuated SARS-CoV-2 challenge model “would show a vaccine works, but at the same time, volunteers won’t have the nasties if it doesn’t,” Cathal Friel, Open Orphan’s executive chair, told BioWorld in May.

Dublin-based Open Orphan labels itself as “the world leader in the testing of vaccines and antivirals using human challenge clinical trials.” The company stock, traded under the symbol ORPH on the London Stock Exchange, closed up four-tenths of a percentage point Tuesday but has soared 100.78% upward in the past six months and 87.59% in the past 12 months. Shares closed July 29 at 13.25 pence (US17 cents).

The Codagenix trial will be held at the London quarantine facility of Hvivo, Open Orphan’s viral contract research organization. Open Orphan touted Hvivo as “one of the few” organizations in the world that has “publicly stated that it is working on testing COVID-19 vaccines for efficacy using human challenge model clinical trials.”

The company recently launched the Hvivo COVID Clear Test, an antibody test for U.K. employers to use helping get employees to return to work.

In May, Open Orphan raised £12 million (US$14.6 million) in a placing to accelerate development of COVID-19 challenge study models, to meet demand from vaccines and therapeutics developers worldwide. Friel said the COVID-19 pandemic is generating unprecedented demand.

“We believe the company has the pipeline to potentially sign up to six COVID-19-related challenge contracts in 2020, with a further six potential contracts in 2021,” Friel said.

The challenge of the human challenge trial

More than 100 leading medical researchers, ethicists and Nobel prize-winning scientists wrote an open letter to head of the U.S. NIH, Francis Collins, in mid-July calling for human challenge trials to accelerate COVID-19 vaccine development. The letter originated with the One Day Sooner campaign, which promotes challenge studies and has 31,254 volunteers in 140 countries saying they would participate.

In May, the World Health Organization said human challenge studies can be valuable for testing vaccines as they are “substantially faster to conduct than vaccine field trials, in part because far fewer participants need to be exposed to experimental vaccines” in order to provide preliminary estimates of efficacy and safety.

The EMA said challenge trials would be useful in various parts of the vaccine development process, in particular in gauging correlates of protection and providing useful information to speed regulatory decisions.

Pfizer and Biontech’s choice

Pfizer and Biontech’s choice of nucleoside-modified messenger RNA BNT-162b2 from the BNT-162-based vaccine program against SARS-CoV-2 follows reviews of the phase I/II trials. Phase I/II preliminary data of BNT-162b1, which encodes an optimized SARS-CoV-2 receptor binding domain (RBD) antigen, turned up dose-dependent immunogenicity as measured by RBD-binding IgG concentrations and SARS-CoV-2 neutralizing antibody titers.

The phase II/III safety and efficacy study will be at a 30-µg dose level in a two-dose regimen and will include up to 30,000 participants from ages 18 to 85. The study covers 120 investigational sites around the globe (it excludes China) and is designed to enroll what the companies call a “diverse population, including participants in areas where there is significant expectation of SARS-CoV-2 transmission.”

The phase II/III trial is designed as a 1-to-1 vaccine candidate to placebo, randomized, observer-blinded study to obtain safety, immune response and efficacy data. The primary endpoints are COVID-19 prevention in those who have not been infected by SARS-CoV-2 prior to immunization and COVID-19 prevention regardless of whether participants have previously been infected by SARS-CoV-2. Secondary endpoints include severe COVID-19 prevention in those groups.

Should the trial be a success, the companies said they will seek emergency use authorization as early as October. The two companies agreed, as part of Operation Warp Speed, to begin delivering 300 million doses of a COVID-19 vaccine in 2021.

BNT-162 is a product of Biontech’s mRNA technology, while Pfizer brings its vaccine development and manufacturing prowess to the table. The development program is evaluating at least four possible vaccines, each with its own combination of mRNA format and antigen target. Two of the four, BNT-162b1 and BNT-162b2, received the FDA’s fast track designation, based on preliminary data from the ongoing phase I/II trials.

HHS makes a reservation in Texas at warp speed

The U.S. Department of Health and Human Services reserved available expanded capacity for manufacturing COVID-19 vaccines at the Center for Innovation in Advanced Development and Manufacturing at the Texas A&M University System by issuing a task order worth about $265 million. That enables Fujifilm Diosynth Biotechnologies (FDB), a contract development and manufacturing organization formed via the partnership of Fujifilm Holdings Corp. and Mitsubishi Corp., both of Tokyo, to more rapidly expand its production capacity at the Texas facilities.

Novavax Inc., of Gaithersburg, Md., recently entered a deal with FDB to manufacture bulk drug substance for NVX-CoV2373, Novavax’s COVID-19 vaccine candidate. FDB’s site in Morrisville, N.C., has begun production of the first batch of NVX-CoV2373. The arrangement falls under Novavax’s $1.6 billion award from the federal government as part of Operation Warp Speed. Novavax is using the money to complete a pivotal phase III trial and hopes to deliver 100 million doses of NVX‑CoV2373 starting as early this year.

HHS reserved the center’s capacity through December 2021 for the government’s partners developing vaccines as part of Operation Warp Speed.

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