Inhaled and nasal Covid-19 vaccine progress

Specialist respiratory drug product news publication OINDP News, has reported progress from several intranasal and inhaled COVID-19 vaccine development programmes.

Altimmune, in collaboration with the University of Birmingham, AL, US, is rapidly moving a single-dose nasal vaccine, AdCOVID, into clinical trials. AdCOVID uses Altimmune’s proprietary intranasal vaccine technology, and it is expected that AdCOVID has the potential to activate multiple arms of the immune system as shown in a recent Phase II clinical study with NasoVAX, an influenza vaccine candidate based on the same platform technology. That study showed potent stimulation of mucosal and cellular immune responses in addition to a strong serum antibody response.

A “solnatide consortium” including Austrian firm APEPTICO has signed a Grant Agreement with the European Commission to accelerate APEPTICO’s lead product, solnatide, for the treatment of patients severely affected by SARS-CoV-2 infection.

Solnatide is being developed by APEPTICO for the treatment of various forms of life-threatening acute pulmonary dysfunction and pulmonary oedema in ARDS patients. In 2013, APEPTICO successfully completed a Phase I clinical study in healthy subjects, and two Phase II clinical studies, one a randomised, double-blinded placebo-controlled trial using inhaled solnatide in mechanically-ventilated ARDS patients with lung oedema, the other a randomised, placebo-controlled pilot study in patients suffering from primary graft dysfunction (PGD) following lung transplantation.

APEPTICO will make solnatide available for the acute and therapeutic treatment of patients suffering from severe symptoms of infection with the SARS-CoV-2 novel coronavirus

Neurimmune and Ethris have partnered to develop inhaled mRNA-encoded, neutralising anti-SARS-CoV-2 antibodies. The collaboration combines Neurimmune’s human antibody development based on high-throughput immunoglobulin sequence analyses from Covid-19 patients who have recovered from the disease and Ethris’ pulmonary SNIM®RNA therapeutics platform, to develop an immunotherapy that produces therapeutic antibodies directly in the lungs.

The companies intend to begin clinical trial supply manufacturing this summer with the first product candidate expected to begin clinical testing in the fourth quarter of 2020, pending regulatory approval.

Finally, CoroFlu, a unique intranasal vaccine against COVID-19, is under development by an international collaboration of virologists at the University of Wisconsin–Madison and the vaccine companies FluGen and Bharat Biotech. Refinement of the CoroFlu vaccine concept and testing in animal models at UW–Madison is expected to take 3-6 months. Bharat Biotech in Hyderabad, India will then begin production scale-up for safety and efficacy testing in humans. CoroFlu could be in human clinical trials by the fall of 2020.

CoroFlu builds on the backbone of FluGen’s flu vaccine candidate known as M2SR. The group will insert gene sequences from SARS-CoV-2, the novel coronavirus that causes the disease COVID-19, into M2SR so that the new vaccine will also induce immunity.

The nasal route of administration mimics the natural route of infection by coronavirus and influenza and activates several modes of the immune system. Intranasal delivery is more effective at inducing multiple types of immune responses than the intramuscular shots that deliver most flu vaccines.

Source press releases and links follow.

ALTIMMUNE PRESS RELEASE

Altimmune is launching a collaboration with the University of Alabama at Birmingham (UAB) on the development of its single-dose, intranasal COVID-19 vaccine, named AdCOVID.

In response to the urgent demand posed by the COVID-19 global pandemic, Altimmune has created a COVID-19 vaccine candidate and is currently preparing for immunogenicity studies and manufacture of Phase I clinical trial material. Initially, Altimmune will work with UAB investigators on preclinical animal studies and characterisation of the vaccine immunogenicity with the goal of enabling a Phase I trial in Q3 2020. Altimmune has significant experience in the development of intranasal vaccines for respiratory pathogens, including NasoVAX, a seasonal and pandemic influenza vaccine candidate, and NasoShield, a vaccine candidate for inhalation anthrax. NasoShield is being developed under a US$133.7 million contract with Biomedical Advanced Research and Development Authority (BARDA).

“It is critical that the biotechnology industry and academic institutions work together to prevent the further spread of COVID-19, and UAB is an ideal partner to support us in this effort,” said Vipin K. Garg, Ph.D., President and Chief Executive Officer. “UAB has an impressive track record of cutting-edge research in virology and immunology, as well as in the clinical development of vaccines. In fact, Altimmune was founded through a technology license from UAB in 1997. We are excited to collaborate with UAB in our efforts and look forward to addressing this crisis together.”

“We are eager to collaborate with Altimmune on this important project,” said Frances E Lund, Charles H McCauley Professor and Chair for the UAB Department of Microbiology. “The expertise and infrastructure at UAB will be invaluable to the rapid progression of this vaccine into clinical studies,” she added.

Six UAB labs will work together on this urgent collaboration with Altimmune. “This project will be our highest priority for the group in the next few months as the goal is to get the data to Altimmune as rapidly as possible, so that they will use the information gained from the preclinical study to design their clinical trial in people,” Lund said.

UAB also has extensive experience in conducting clinical studies of vaccines and has participated in studies sponsored by the Vaccine Evaluation and Trial Unit, part of the National Institute of Allergy and Infectious Diseases at the US National Institutes of Health.

AdCOVID is a single-dose, intranasal vaccine candidate designed to protect against COVID-19, the disease caused by the SARS-CoV-2 virus. By utilising the Altimmune’s proprietary intranasal vaccine technology, it is expected that AdCOVID has the potential to activate multiple arms of the immune system as shown in a recent Phase II clinical study with NasoVAX, an influenza vaccine candidate based on the same platform technology. That study showed potent stimulation of mucosal and cellular immune responses in addition to a strong serum antibody response. In addition, our platform vaccines (NasoVAX and NasoShield) have shown an excellent stability profile and, when combined with the simple intranasal route of administration, may allow for efficient and inexpensive distribution of the vaccine.

Source: OINDP News.

Link to Press Release.

APEPTICO PRESS RELEASE

APEPTICO has signed, together with the “solnatide consortium”, the Grant Agreement with the European Commission to accelerate the process of making APEPTICO’s proprietary investigational medicinal product (IMP) solnatide available for medical treatment of patients severely affected by SARS-CoV-2 infection.

APEPTICO is a privately-held biotechnology company based in Austria, developing peptide-based medicinal products to treat life-threatening pulmonary dysfunctions, such as severe respiratory failure, oedematous respiratory failure (lung oedema), acute respiratory distress syndrome (ARDS), primary graft dysfunction (PGD) following lung transplantation, high altitude pulmonary oedema (HAPE) and pseudohypoaldosteronism type 1B (PHA1B).

APEPTICO’s lead compound, the therapeutic molecule solnatide (INN) is being developed by APEPTICO for the treatment of various forms of life-threatening acute pulmonary dysfunction and pulmonary oedema in ARDS patients. In 2013, APEPTICO successfully completed a Phase I clinical study in healthy subjects, proving the safety of solnatide. APEPTICO subsequently successfully completed two Phase II clinical studies, one a randomized, double-blinded placebo-controlled trial using inhaled solnatide in mechanically-ventilated ARDS patients with lung oedema, the other a randomised, placebo-controlled pilot study in patients suffering from primary graft dysfunction (PGD) following lung transplantation.

Clinical data gathered so far from hospitalised patients suffering from COVID-19 have revealed that 20% suffer from ARDS and the involvement of pulmonary oedema is evidenced by post mortem sampling of a patient who succumbed to COVID-19 infection. The observed mortality rate for ARDS is 20-30%. At present no medicine has been approved specifically for the therapeutic treatment of pulmonary permeability oedema or ARDS.

The Grant Agreement was made available via the Horizon2020 programme “Advancing knowledge for the clinical and public health response to the 2019-nCoV epidemic” (https://ec.europa.eu/commission/presscorner/detail/en/ip_20_386).

In this emergency situation in hospitals across Europe, APEPTICO will make solnatide IMP available for the acute and therapeutic treatment of patients suffering from severe symptoms of infection with the SARS-CoV-2 novel coronavirus.

Commenting on the EU Grant Agreement, Bernhard Fischer, CEO of APEPTICO, stated: “We are very happy that the European Commission agreed with APEPTICO and the “solnatide-consortium” to financially support us in the consortium’s effort to make solnatide IMP available for the treatment of severely affected patients with the new coronavirus. By offering our solnatide IMP for the immediate treatment of patients, APEPTICO commits its responsibilities towards the society.”

Source: OINDP News.

Link to Press Release.

NEURIMMINE/ETHRIS PRESS RELEASE

Neurimmune and Ethris announced an exclusive partnership to develop mRNA-encoded, neutralising anti-SARS-CoV-2 antibodies administered by inhalation for the treatment of Covid-19. The collaboration brings together Neurimmune’s expertise in developing human antibodies based on high-throughput immunoglobulin sequence analyses from Covid-19 patients who have recovered from the disease with Ethris’ proprietary and unique pulmonary SNIM®RNA therapeutics platform. Both companies will work together to rapidly develop an immunotherapy designed to produce therapeutic antibodies directly in the lungs of affected patients.

Enabled by Ethris’ mRNA technology, the production of specific, neutralizing antibodies directly in patients’ lungs provides the opportunity to significantly impact the viral lung disease that is the primary driver of morbidity and mortality. The planned treatment could be effective in all Covid-19 patients.

Neurimmune is identifying human anti-SARS-CoV-2 antibodies from the immune cells of recovered Covid19 patients using its RTMTM Technology platform. Potent neutralizing antibodies will be translated into therapeutic SNIM®RNA products for inhalation. Based on current development plans, the first product candidate is expected to begin clinical testing in the fourth quarter of 2020, pending regulatory approval.

“The speed and precision that mRNA technologies provide make them well-suited for designing therapeutic candidates to treat the Covid-19 pandemic. We have built a strong platform for developing potent mRNAs to treat pulmonary disorders and local delivery in the lung may provide significant therapeutic benefits. By combining our approach with Neurimmune’s proven human antibody technology, we are well- ositioned to expediently develop a treatment that could save lives,” said Ethris CEO, Dr. Gita Dittmar.

“Covid-19 patients with lung disease require a safe and effective therapy urgently. Together, we aim to develop this novel treatment at the highest speed possible. Time is of the essence.” said Roger Nitsch, Neurimmune’s CEO.

Jan Grimm, CSO of Neurimmune added: “With Ethris’ pulmonary SNIM®RNA technology we can leverage state-of-the-art technology to express human SARS-CoV-2 neutralizing antibodies directly in the lung to rapidly achieve effective pulmonary antibody concentrations.”

Dr. Carsten Rudolph, CSO of Ethris added: “This collaborative effort is underscored by the immense need for a treatment and our combined commitment to put a therapy into the hands of the doctors and nurses who are fighting this disease across the globe. We are two companies among many that are applying innovation and speed to make a valuable contribution to curb this pandemic, and we thank our partners at Neurimmune for joining us for this effort.”

Under the collaboration agreement, Neurimmune and Ethris will jointly conduct research and development activities while sharing costs and revenues resulting from the collaboration. The companies intend to initiate manufacturing of the drug product for clinical trials this summer, and will inform about progress made as the collaboration advances.

Source: OINPD News.

Link to Press Release.

UW–MADISON, FLUGEN, BHARAT PRESS RELEASE

An international collaboration of virologists at the University of Wisconsin–Madison and the vaccine companies FluGen and Bharat Biotech has begun the development and testing of a unique vaccine against COVID-19 called CoroFlu.

CoroFlu will build on the backbone of FluGen’s flu vaccine candidate known as M2SR. Based on an invention by UW­Madison virologists and FluGen co-founders Yoshihiro Kawaoka and Gabriele Neumann, M2SR is a self-limiting version of the influenza virus that induces an immune response against the flu. Kawaoka’s lab will insert gene sequences from SARS-CoV-2, the novel coronavirus that causes the disease COVID-19, into M2SR so that the new vaccine will also induce immunity against the coronavirus.

Refinement of the CoroFlu vaccine concept and testing in laboratory animal models at UW–Madison is expected to take three to six months. Bharat Biotech in Hyderabad, India will then begin production scale-up for safety and efficacy testing in humans. CoroFlu could be in human clinical trials by the fall of 2020.

Four Phase I and Phase II clinical trials involving hundreds of subjects have shown the M2SR flu vaccine to be safe and well tolerated. This safety profile, M2SR’s ability to induce a strong immune response, and the ability of influenza viruses to carry sequences of other viruses make M2SR an attractive option for rapidly developing CoroFlu as a safe and effective SARS-CoV-2 vaccine.

“We are going to modify M2SR by adding part of the coding region for the coronavirus spike protein that the virus uses to latch onto cells and begin infection,” says Gabriele Neumann, a senior virologist in Kawaoka’s lab and co-founder of FluGen. “CoroFlu will also express the influenza virus hemagglutinin protein, which is the major influenza virus antigen, so we should get immune responses to both coronavirus and influenza.”

M2SR is a unique form of the flu virus. It lacks a gene called M2, which restricts the virus to undergoing only a single round of replication in cells.

“The single replication means the virus can enter the cell, but it can’t leave,” says FluGen co-founder, president and CEO Paul Radspinner. “So, in essence it tricks the body into thinking it’s infected with flu, which triggers a full immune response. But since it can’t replicate further, you don’t get sick.”

CoroFlu, like M2SR, will be delivered intranasally. This route of administration mimics the natural route of infection by coronavirus and influenza and activates several modes of the immune system. Intranasal delivery is more effective at inducing multiple types of immune responses than the intramuscular shots that deliver most flu vaccines.

The Kawaoka group will insert genetic sequences from SARS-CoV-2 into M2SR and then assess CoroFlu’s safety and efficacy in animal models at UW–Madison’s Influenza Research Institute. The institute has a high-level biosafety facility designated Biosafety Level 3 Agriculture with the ability to safely handle and study pathogens like highly pathogenic influenza viruses and the novel coronavirus.

M2SR was developed by FluGen and includes technology exclusively licensed through the Wisconsin Alumni Research Foundation (WARF), which manages patents for UW–Madison. “To confront a global challenge, this is collaborative discovery at its best,” says Erik Iverson, CEO of WARF. “The partners in this endeavor — University of Wisconsin researchers, a biotech startup, and an international vaccine developer — are moving forward with a sense of urgency and integrity incumbent upon us as scientists and world citizens.”

Bharat Biotech has commercialized 16 vaccines, including a vaccine developed against the H1N1 flu that caused the 2009 pandemic. FluGen will transfer its existing manufacturing processes to Bharat Biotech to enable the company to scale up production and produce the vaccine for clinical trials. Bharat Biotech will manufacture the vaccine, conduct clinical trials and prepare to produce the vaccine for global distribution. Bharat Biotech can produce almost 300 million doses per year.

“The core mission of Bharat Biotech is to apply innovative technologies in addressing the healthcare concerns of the developing world and to provide them with affordable, high quality vaccines and therapeutics,” says Raches Ella, head of business development for the company. “Ninety percent of our vaccines are sold in lower middle-income countries with affordable pricing being core to our business model. We will fervently work toward the successful development of an efficacious COVID-19 vaccine.”

Source: OINDP News.

Link to Press Release on Businesswire.