Type: Single-dose, intranasal vaccine designed to provide systemic immunity by expressing the receptor binding domain (RBD) of the SARS-CoV-2 virus spike protein. Altimmune based the vaccine on proprietary platform technology that was applied in developing NasoVAX™, the company’s influenza vaccine candidate that showed positive Phase IIa results.
2021 Status: Altimmune said May 10 announced positive preclinical results showing that a single intranasal dose of AdCOVID provided sterilizing immunity in the lungs of vaccinated mice, in a preclinical study of AdCOVID in a SARS-CoV-2 challenge model of infection. By contrast, dense pulmonary infection and disease developed in the lungs of non-vaccinated mice following infection with SARS-CoV-2.
In the study, performed in collaboration with University of Alabama at Birmingham, K18-hACE2 transgenic mice were vaccinated with a single intranasal dose of AdCOVID and challenged one month later with live SARS-CoV-2 virus. When the lungs of the mice were evaluated for infectious SARS-CoV-2 virus, no detectable levels of infectious virus were observed in the lungs of vaccinated mice, representing a greater than 1 million-fold reduction of infectious virus compared to the non-vaccinated controls.
Scot Roberts, PhD, Altimmune’s Chief Scientific Officer, stated that the company expects to report results later in the second quarter from its ongoing Phase I trial of AdCOVID (NCT04679909).
Altimmune said March 15 disclosed positive preclinical data from a K18-hACE2 transgenic mouse in studies at Altimmune’s collaborating institutions, the University of Alabama at Birmingham (UAB) and Saint Louis University (SLU). The studies showed that a single intranasal dose of AdCOVID provided 100% protection against a lethal challenge from the SARS-CoV-2 virus, and that all animals that received AdCOVID survived and had no observed weight loss. The studies were conducted in the labs of James Brien Ph.D., and Amelia Pinto Ph.D., within the Department of Molecular Microbiology & Immunology at SLU.
Initial immunogenicity analysis showed mean antibody levels of about 1 mg/mL, suggesting that the serum IgG antibody response against the spike protein was robust, similar to what was reported in prior Company announcements. In a separate study at UAB in the lab of Frances Lund, PhD, conducted in the same animal model, a single intranasal dose of AdCOVID resulted in a greater than 1000-fold reduction in replicating virus in the nasal cavity and respiratory tract following infection with SARS-CoV-2.
Altimmune expanded its AdCOVID manufacturing collaboration with Lonza on March 12, as Lonza has agreed to commission a dedicated manufacturing suite for clinical and commercial production of AdCOVID at its facility near Houston. “We are building extra capacity and redundancy into our manufacturing to support potential late-stage clinical trials with AdCOVID and potential future commercial supply,” stated Vyjayanthi Krishnan, PhD, Vice President of Product Development for Altimmune.
Altimmune said February 25 it had commenced enrollment in a Phase I trial (NCT04679909) designed to evaluate the safety and immunogenicity of AdCOVID in up to 180 healthy adult volunteers between the ages of 18 and 55. Participants will receive AdCOVID at one of three dose levels administered as a nasal spray. In addition to the primary study endpoint of safety and tolerability, Altimmune said, the immunogenicity of AdCOVID will be evaluated by serum IgG binding and neutralizing antibody titers, mucosal IgA antibody from nasal samples, and T cell responses.
Altimmune expects to release a full data readout from the Phase 1 study in the second quarter. The FDA cleared the company’s IND application for the trial a week earlier.
2020 Status: Altimmune acknowledged December 23 that the FDA issued a clinical hold on AdCOVID pending the company’s submission to the agency of undisclosed protocol modifications and additional chemistry, manufacturing and controls (CMC) data. The company said it has agreed to each of the FDA’s requests in a response to the agency’s clinical hold letter, received a day earlier, and did not anticipate a significant impact on its overall clinical development timeline “at this time.”
“We look forward to working with the FDA and will continue preparing to commence our planned Phase I clinical trial [NCT04679909] of AdCOVID,” Altimmune President and CEO Vipin K. Garg, PhD, stated.
On November 10, Altimmune entered into an agreement of undisclosed value with Lonza for the manufacturing of AdCOVID. “We are excited about the potential of our AdCOVID vaccine candidate and are actively focused on expanding our network of strategic manufacturing partners to ensure Altimmune’s commercial readiness to supply vaccine in 2021 should our clinical data support this advancement,” said Vyjoo Krishnan, PhD, Vice President of Product Development for Altimmune.
Altimmune President and CEO Vipin K. Garg, PhD, said in November that the company planned to commence a clinical study of AdCOVID in the fourth quarter of 2020, with a data readout anticipated in the first quarter of 2021.
In July, Altimmune entered into an agreement to manufacture AdCOVID with Vigene Biosciences, a Rockville, MD-based CDMO that specializes in viral vectors, and recently opened a new manufacturing facility. “We are in the process of expanding our capacity so that we can support Altimmune beyond clinical development into commercial scale manufacturing,” stated Zairen Sun, PhD, Vigene’s President and CEO.
Altimmune added that it is initiating scale up of manufacturing of AdCOVID for advanced clinical trials and commercial production. The company said it was “actively engaged” in discussions with additional strategic manufacturing partners, with the goal of producing at least 100 million doses of AdCOVID in 2021.
The agreement came a week after Altimmune said it planned to begin manufacturing of AdCOVID and advance the vaccine candidate into a Phase I safety and immunogenicity study in the fourth quarter, following positive results from preclinical studies conducted with UAB.
The preclinical studies showed strong serum neutralizing activity and potent mucosal immunity in the respiratory tract, Altimmune said. AdCOVID elicited a strong systemic antibody response against RBD in mice, achieving serum Immunoglobulin G (IgG) antibody concentrations greater than 800 micrograms per milliliter 14 days after administration of a single intranasal dose. AdCOVID also stimulated serum viral neutralization titers of 1:320 by Day 28, and two times higher than the titer recommended by the FDA for investigational convalescent plasma as a treatment for severe COVID-19.
In a separate study conducted by UAB, a single intranasal dose of AdCOVID stimulated a 29-fold induction of mucosal immunoglobulin A (IgA) in bronchoalveolar fluid of vaccinated mice: “The potent stimulation of mucosal IgA immunity in the respiratory tract may be crucial to effectively block infection and transmission of the SARS-CoV-2 virus given that the nasal cavity is a key point of entry and replication for the SARS-CoV-2 virus,” stated Frances Lund, PhD, Charles H. McCauley Professor and Chair, Department of Microbiology at UAB, and lead investigator for preclinical testing of AdCOVID.
Also, increases in CD8+ and CD4+ T cells, dendritic cells and natural killer cells were sees in the respiratory tract, while germinal center and memory B cells as well as T follicular helper cells, all associated with long-lived antibody responses, were observed in regional lymph nodes and the spleen.
In March, Altimmune announced plans to partner with UAB to develop AdCOVID. The company said it is preparing for immunogenicity studies and manufacture of Phase I clinical trial material. Initially, Altimmune will work with UAB investigators on preclinical animal studies and characterization of the vaccine immunogenicity with the goal of enabling a Phase I trial in the third quarter.
Altimmune said in February it completed the design and synthesis of the vaccine, and was “actively engaged in discussions with a number of potential partners.” Six UAB labs will work with Altimmune on the urgent collaboration, the University said.
COVID-19: 200 Candidates and Counting
To navigate through the >200 potential therapeutic and vaccine options for COVID-19, GEN has grouped the candidates into four broad categories based on their developmental and (where applicable) clinical progress:
● FRONT RUNNER – the most promising therapeutics/vaccines based on clinical progress, favorable data or both.
● DEFINITELY MAYBE – earlier phases with promising partners, or more advanced candidates in development that have generated uneven data
● KEEPING AN EYE ON… – interesting technology, attracting notable partners, or both, but preliminary data.
● TOO SOON TO TELL – longshots pending additional experimental and/or clinical data.
GEN has also tagged the most common treatment types: