Despite being founded just last June, Belgian biotech ExeVir is making serious headway in the race to develop effective antibodies against Covid-19. The companys llama-derived antibody, XVR011, is currently being trialled in healthy individuals and hospitalised Covid-19 patients and the data so far looks promising.
The antibodies were originally extracted from a llama named Winter, who is now being left to his own devices at a private animal park in Belgium as the antibodies can be synthesised in a lab. The small, llama-derived nanobodies have demonstrated strong neutralising activity against Covid-19 and all of its variants of concern. ExeVir, which was spun out from the Flanders Institute for Biotechnology, has moved its lead candidate from laboratory tests to human clinical trials at an impressive pace, and beyond the current pandemic, the firm is hoping to build a broader platform for the treatment of infectious diseases of all kinds, both viral and bacterial.
Pharmaceutical Technology speaks to ExeVir CEO Torsten Mumenbrauer about the companys research and why XVR011 has the edge over other Covid-neutralising antibody programmes.
Darcy Jimenez: How did research into this therapeutic candidate begin, and why were llama-derived antibodies chosen?
Torsten Mummenbrauer: The technology as such is pretty old. It had been invented at the University of Brussels almost 20 years ago, then the Flanders Institute for Biotechnology (VIB) in Ghent took it on board and continue to develop the technology.
The big benefit of the technology is the small size of the nanobodies, and the resulting advantages. In our special case, we have a very specific epitope on the spike protein, which is targeted by our lead candidate. And because the molecule is so much smaller than human antibodies, it can bind in this small groove or niche, and that makes it special. Its applicable for any use thats why we believe its a platform technology which can be used broadly in infectious disease development.
The fact that the nanobody is that much smaller also makes it applicable for different presentation in humans so you can consider inhaled versions, we will develop a subcutaneous version, and you can fuse it to the Fc receptor to make it look like a human antibody. Thats what we have done with our lead molecule, specifically to stabilise it. When its fused to an Fc, its roughly only half of the size of a human antibody, so if you put a certain amount per dose in your therapeutic approach, you have roughly double the number of molecules in the patient.
Then you can think about future variations or design changes. The FDA advised, for Covid-19 products, to go for a combination product thats what we see with the Regeneron product, which is a combination of two [monoclonal antibodies], and Lillys as well. In our case, we could simply fuse two different nanobodies to one molecule or on one Fc and mimic the combination approach, but keep all the advantages of the technology.
DJ: What have studies shown so far about the antibodys efficacy against Covid-19?
TM: We started off against the wild type, the Wuhan strain, of course, and we showed efficacy in picomolar range in the hamster model. We have done the same experiment against Alpha, Beta, Gamma and Delta variants, and we see no change. We have very much the same potency against all variants which are [circulating] so far. We are looking at the variants of interest, and well follow up and test these as well.
The key importance here is the epitope of your binder. If this epitope starts to mutate, then that allows the virus to escape. And this is what happens on the antibodies from Regeneron, which were originally derived from plasma from convalescent patients. They are all binding to the outer part of the RBD (receptor binding domain), and this is where you find the mutation hotspots of the virus.
We are on a side niche, and we are not impacted by any of these mutations; we have a crystal structure, and we can clearly show that these mutation hotspots are in other areas of the virus. We have shown on sequencing data that our epitope is very highly conserved over the SARS-COV virus family.
An interesting aspect is that originally, our llama Winter had been immunised against SARS-COV-1 already four or five years ago thats the reason why the company could be that fast. The library against SARS-COV-1 existed already in February last year, when the SARS-COV-2 sequence was published. So we immediately did a screen, and we found 100% cross-reactive binders, and that resulted in our lead candidate. Thats probably another reason why we have this highly conserved and very stable epitope, because its conserved on the whole virus family.
We of course are looking into the sequencing database available for all virus isolates worldwide, and there you can see the mutation hotspots coming. In our binding area there is extremely limited mutation frequency, so it seems that this highly conserved epitope is important for the viability of the virus itself, and thats probably the reason why its so stable.
DJ: Dosing of Phase I trial participants began last month, and hospitalised Covid-19 patients were also dosed recently. Are you confident about the antibody being studied in a hospital setting?
TM: We decided a while ago to silence our Fc component, and Ive mentioned that weve fused the Fc of the antibody to the nanobody thats specifically for safety reasons. Its one of our key differentiators compared to other antibodies, where you have the concern of antibody-derived enhancement of the disease, because of the activation of the immune system through the antibody. Our Fc is silenced, so we just neutralise the virus and we do not activate the immune system.
Were extremely confident about [the study], and we strongly believe that the early-stage, mild-to-moderate hospitalised patients have the highest medical need, because there you want to avoid progression of the disease and ICU, of course.
To add on to that, the first cohort in Phase I healthy subjects have been completely dosed without any severe side effects. There is a bit of redness at the infusion site, which is normal for antibodies, and the same [was found] for the first hospital patient who has been dosed.
DJ: Developing a promising candidate to help combat the pandemic is an impressive feat for a company that was founded only last year. What else is ExeVir working on that youre particularly excited about?
TM: This is our lead candidate; we were focusing very much over the last year on the lead, otherwise it wasnt going to happen. We were always thinking, if you want to make a difference in a disease like Covid-19, in a crisis, you need to be extremely fast. And so that has to be the focus, but we definitely see this as a platform technology to fight infectious diseases, and there we split that into two parts.
One is the future of pandemic preparedness: I strongly believe that people have realised that vaccines, in the case of a pandemic outbreak, are an important component of a response, but it also requires therapeutics. If you want to ringfence a local outbreak, a therapeutic is much more efficacious. You dont need to wait for onset of immunity, you can use antibodies in prophylactic and therapeutic settings, and I think we have proven with the pre-immunisation of the llama that you can be very fast with this technology.
We definitely want to be part of pandemic preparedness of the future, but thats not where you can really build the commercial future of a company in my view, because you dont know if or when your pre-developed product might be required. So we are also working on a pipeline for infectious diseases with high medical need, and we are in the last step, I would say, of the process to come up with a shortlist of candidates. It will target infectious diseases with the highest medical need and hospitalisation relevance, so the technology can be used against bacterial diseases as well as viral. There is an ongoing programme on universal flu at VIB, which is very exciting for us, so there will be definitely a strong pipeline path for the next year beyond Covid-19.
We are really proud to demonstrate with [XVR011] that you can bring a molecule from early R&D and preclinical to a patient within a year. And for a small company, under all the circumstances of the pandemic, we believe thats a really cool achievement.
Milling Systems for Pharmaceutical Powders and Granulates
28 Aug 2020
Tamper-Evident Solutions for Pharmaceutical Packaging
28 Aug 2020
See the original post:
ExeVir Q&A: the llama-derived antibody that could fight Covid-19 - Pharmaceutical Technology
- As 2024 Travel Hits Pre-Covid Levels, Here's When To Go To Europe - Forbes - March 10th, 2024 [March 10th, 2024]
- Comparison of Impressions of COVID-19 Vaccinations Stratified by the Number of Vaccinations Among Japanese ... - Cureus - March 10th, 2024 [March 10th, 2024]
- Effect of the COVID-19 pandemic on mental health visits in primary care: an interrupted time series analysis from nine ... - The Lancet - March 10th, 2024 [March 10th, 2024]
- Faith and rehab keep Southwick woman on path to recovery from COVID - MassLive.com - March 10th, 2024 [March 10th, 2024]
- China to draw on Covid-19 experience to tackle future pandemics - theSun - March 10th, 2024 [March 10th, 2024]
- Free COVID tests through USPS are ending todayhere's where to get tests online - Reviewed - March 10th, 2024 [March 10th, 2024]
- Concern about COVID reaches record low across political spectrum: Survey - The Hill - March 10th, 2024 [March 10th, 2024]
- He Had 217 Covid Shots Without Side Effects, Study Finds - The New York Times - March 10th, 2024 [March 10th, 2024]
- A Man Got 217 COVID-19 Vaccines. Here's What Happened - TIME - March 10th, 2024 [March 10th, 2024]
- German man vaccinated 217 times against covid with no ill effects - The Washington Post - March 10th, 2024 [March 10th, 2024]
- Andrew Cuomo Faces House Subpoena Over Covid Deaths in Nursing Homes - The New York Times - March 10th, 2024 [March 10th, 2024]
- It's been 4 years since COVID hit Michigan. For Long COVID patients, the pandemic isn't over. Michigan Advance - Michigan Advance - March 10th, 2024 [March 10th, 2024]
- 4th Anniversary of the Covid-19 Pandemic - erienewsnow.com - March 10th, 2024 [March 10th, 2024]
- Reflecting on 4 years of the COVID-19 pandemic and discussing what's to come - WBUR News - March 10th, 2024 [March 10th, 2024]
- CDC shortens 5-day COVID isolation, updates guidance on masks and testing in new 2024 recommendations - CBS News - March 10th, 2024 [March 10th, 2024]
- Father, daughter convicted in fraud related to COVID-19 relief - The Cincinnati Enquirer - February 7th, 2024 [February 7th, 2024]
- Supreme Court to weigh whether Covid misinformation is protected speech - STAT - February 7th, 2024 [February 7th, 2024]
- Oklahoma leads country in long Covid - 2 News Oklahoma KJRH Tulsa - February 7th, 2024 [February 7th, 2024]
- MCFR firefighter dies after battle with COVID-19 - WCJB - February 7th, 2024 [February 7th, 2024]
- Audio-based AI classifiers show no evidence of improved COVID-19 screening over simple symptoms checkers - Nature.com - February 7th, 2024 [February 7th, 2024]
- Hidden death toll of COVID-19 pandemic revealed - Earth.com - February 7th, 2024 [February 7th, 2024]
- Switching arms improves effectiveness of two-dose vaccinations, OHSU study suggests - OHSU News - February 7th, 2024 [February 7th, 2024]
- Tributes paid to Irish health official 'central' to EU Covid-19 response - The Irish Times - February 7th, 2024 [February 7th, 2024]
- Court: Not wearing mask during COVID-19 health emergency isn't protected speech - Honolulu Star-Advertiser - February 7th, 2024 [February 7th, 2024]
- One arm or two? How you get vaccinated may make a difference - The Seattle Times - February 7th, 2024 [February 7th, 2024]
- 70% of kindergarteners didn't pass readiness test in pandemic, study estimates - University of Minnesota Twin Cities - February 7th, 2024 [February 7th, 2024]
- USS Theodore Roosevelt sailors roam free on Guam for first time since COVID-19 outbreak - Stars and Stripes - February 7th, 2024 [February 7th, 2024]
- Pandemic linked to 14% increase in underweight children in India - Medical Xpress - February 7th, 2024 [February 7th, 2024]
- COVID and travel: Should I still wear a mask on the plane? - USA TODAY - February 7th, 2024 [February 7th, 2024]
- Vaccine hesitancy and equity: lessons learned from the past and how they affect the COVID-19 countermeasure in ... - Globalization and Health - February 7th, 2024 [February 7th, 2024]
- Increase in STIs Among Adolescents Witnessed During COVID-19 Pandemic - Drug Topics - February 7th, 2024 [February 7th, 2024]
- VDH: COVID deaths not seeing decline - Vermont Biz - February 7th, 2024 [February 7th, 2024]
- US outpatient care for serious mental health issues declined during COVID-19 - University of Minnesota Twin Cities - February 7th, 2024 [February 7th, 2024]
- COVID-19 Vaccination in a Patient With Gluten Enteropathy: A Case Report - Cureus - February 7th, 2024 [February 7th, 2024]
- COVID-19 cases drop, but still lots of flu, RSV cases in Erie County - GoErie.com - February 7th, 2024 [February 7th, 2024]
- Lives versus livelihoods: The COVID-19 trade-off from an epidemiological-economic perspective - CEPR - February 7th, 2024 [February 7th, 2024]
- Weatherhead's Jonathan Ernest notes economic changes of childcare facilities following COVID-19 pandemic - The Daily | Case Western Reserve University - February 7th, 2024 [February 7th, 2024]
- U.S. adults face distress, unequal mental health care access during the COVID-19 era - News-Medical.Net - February 7th, 2024 [February 7th, 2024]
- Simnotrelvir to reduces the symptoms of mild to moderate COVID-19 - 2 Minute Medicine - February 7th, 2024 [February 7th, 2024]
- Vaccine Effectiveness: Which COVID-19 Shots Offer the Most Protection? - SciTechDaily - February 7th, 2024 [February 7th, 2024]
- New evidence confirms COVID-19 vaccination in pregnancy is safe for babies - Gavi, the Vaccine Alliance - February 7th, 2024 [February 7th, 2024]
- Audit Committee co-chairs, Evers at odds over interest from COVID-19 funds - WisPolitics.com - February 7th, 2024 [February 7th, 2024]
- Evaluation of Olfactory Dysfunction Among COVID-19 Patients in Baghdad, Iraq - Cureus - February 7th, 2024 [February 7th, 2024]
- COVID-19's impact on early education: Retrospective study shows decrease in kindergarten readiness - News-Medical.Net - February 7th, 2024 [February 7th, 2024]
- Rutgers researchers work on breakthrough COVID-19 treatment | Video - NJ Spotlight News - February 7th, 2024 [February 7th, 2024]
- Curious Iowa: Has the state spent all of its COVID-19 relief funding? - The Gazette - October 16th, 2023 [October 16th, 2023]
- Accelerating into Immunization Agenda 2030 with momentum from ... - Infectious Diseases of Poverty - BioMed Central - October 16th, 2023 [October 16th, 2023]
- Study Uncovers Why Young Children Suffer Less Severe COVID-19 - Technology Networks - October 16th, 2023 [October 16th, 2023]
- Wenstrup, Select Subcommittee Majority Members Investigate ... - House Committee on Oversight and Reform | - October 16th, 2023 [October 16th, 2023]
- With COVID-19 emergency orders lifted, employers seek guidance ... - Hartford Business Journal - October 16th, 2023 [October 16th, 2023]
- Computer-aided diagnosis of chest X-ray for COVID-19 diagnosis in ... - Nature.com - October 16th, 2023 [October 16th, 2023]
- Maternal COVID-19 Vaccination, Infection Boosts Infant Antibody ... - Contagionlive.com - October 16th, 2023 [October 16th, 2023]
- Three Middlesex County Individuals Admit COVID-19 Fraud ... - Department of Justice - October 16th, 2023 [October 16th, 2023]
- Seventeen Broward Sheriff's Office Employees Charged with COVID ... - Department of Justice - October 16th, 2023 [October 16th, 2023]
- New COVID-19 Booster and Flu Shot Available at Select Public ... - Mecklenburg County (.gov) - October 16th, 2023 [October 16th, 2023]
- Ban on COVID vaccine mandates by private businesses, including ... - The Texas Tribune - October 16th, 2023 [October 16th, 2023]
- What Are the Side Effects of the 2023 COVID Vaccine? Experts ... - Good Housekeeping - October 16th, 2023 [October 16th, 2023]
- Covid inquiry: Bereaved families relief as High Court dismisses Cabinet Office JR - openDemocracy - July 6th, 2023 [July 6th, 2023]
- UK health agency failed to account for 3.3bn of Covid inventory, say MPs - Financial Times - July 6th, 2023 [July 6th, 2023]
- COVID-19 Working Paper: Obesity Prevalence Among U.S. Adult ... - usda.gov - July 6th, 2023 [July 6th, 2023]
- California Changes Definition of COVID-19 Outbreak Easing the ... - Fisher Phillips - July 6th, 2023 [July 6th, 2023]
- New Study Shows Robust Pandemic Preparedness Strongly Linked ... - Nuclear Threat Initiative - July 6th, 2023 [July 6th, 2023]
- COVID-19 Infection Reduces the Risk of UTIs, Bacteremia, and ... - Contagionlive.com - July 6th, 2023 [July 6th, 2023]
- Europe Phases Out COVID-19 Flexible Regulations - Pharmaceutical Technology Magazine - July 6th, 2023 [July 6th, 2023]
- Travel Pains and COVID: How to Decide if You're Ready to Travel - CreakyJoints - July 6th, 2023 [July 6th, 2023]
- COVID Depression and Anxiety | Johns Hopkins Medicine - April 17th, 2023 [April 17th, 2023]
- Man declared dead due to Covid found 'shockingly' alive after 2 years in MP - Hindustan Times - April 17th, 2023 [April 17th, 2023]
- Senate votes to end Covid-19 emergency, 3 years after initial declaration - CNN - March 31st, 2023 [March 31st, 2023]
- DC COVID-19 centers closing Friday: Here's what you need to know - WJLA - March 31st, 2023 [March 31st, 2023]
- Can grade retention help with COVID-19 learning recovery in schools? - Brookings Institution - March 28th, 2023 [March 28th, 2023]
- On 3-year anniversary of COVID-19 in NC, Winston-Salem woman shares story of loss and healing after losing 2 loved ones - WXII12 Winston-Salem - March 4th, 2023 [March 4th, 2023]
- Oregon, Washington will lift mask requirements in health care settings on April 3 - KATU - March 4th, 2023 [March 4th, 2023]
- WHO says all theories for COVID origin 'remain on table' as lab leak theory gains traction - Sky News - March 4th, 2023 [March 4th, 2023]
- New COVID-19 omicron subvariant XBB.1.5 sweeping the nation, making up majority of cases - ABC Action News Tampa Bay - February 15th, 2023 [February 15th, 2023]
- Man gets 21 years in prison for stabbing wife in the Ozarks over COVID-19 stimulus check and their children - Law & Crime - February 15th, 2023 [February 15th, 2023]
- Healthline: Medical information and health advice you can trust. - January 2nd, 2023 [January 2nd, 2023]
- China can expect repeat Covid infections with new strains on the way: experts - South China Morning Post - January 2nd, 2023 [January 2nd, 2023]
- PCR tests for travellers reintroduced around the world as Covid-19 cases surge - The National - January 2nd, 2023 [January 2nd, 2023]
- Covid-19 surge after Covid-19 surge has made it impossible for US hospitals to plan for the future - Vox.com - January 2nd, 2023 [January 2nd, 2023]
- COVID-19 in China: Demand for a particular fruit rises as people seek natural remedies to fight the virus - WION - December 21st, 2022 [December 21st, 2022]