Respiratory complications caused by COVID-19 can propel a patient from a mild cough one day to a ventilator and an ICU only 10 days later.
As countries around the world work to stockpile ventilators and citizens continue social distancing measures, biopharma companies are tackling the development of fast-acting therapeutics to disrupt a dire disease trajectory in hospitalized patients.
An industry-wide frantic race has ensued. On March 5, BioWorld reported that there were approximately 30 therapeutics and vaccines in development for COVID-19. As of April 28, there were 343 total: 249 therapeutics and 94 vaccines. Of the therapeutics, several are targeting respiratory complications that can quickly cascade into severe inflammatory responses, primarily driven by T cells, in the lung.
Also known as a cytokine storm, these inflammatory responses arrest breathing, cause severe pneumonia, hypoxemic respiratory failure and acute respiratory distress syndrome (ARDS), making it difficult for oxygen to reach vital organs. For survivors, it can lead to life-long compromised pulmonary function.
What weve learned from the experts is that once you go into the hospital there are two pathways here, said Sanjay Shukla, president and CEO of San Diego-based Atyr Pharma Inc. Some patients with severe pneumonia recover, but a smaller segment of those infected become worse and need help in down-regulating the inflammatory response. Thats also where hospitals are struggling right now with regards to how much capacity they have for those kinds of patients.
Atyrs neuropilin-2 modulator
Atyr announced April 21 that the FDA accepted its investigational new drug (IND) application for a phase II trial of ATYR-1923 in COVID-19 patients with severe respiratory complications.
The drug works by engaging immune cells that are involved in an inflammatory response, Shukla told BioWorld.
In January, the company signed a $175 million deal with Tokyo-based Kyorin Pharmaceutical Co. Ltd. to develop the product for interstitial lung diseases in Japan, with plans to move into a registrational trial in pulmonary sarcoidosis (PS) pending phase Ib/IIa data expected later in the year. At that time, little was known outside of China about the SARS-CoV-2 infection.
Now, the data from the PS trial, along with the expected timelines for about 300 other clinical trials, have been delayed as a result of the pandemic. Shukla said a restart in the next month or two of the PS trial will result in about a quarter delay in the final readouts, originally expected for the third quarter of 2020.
When the initial reports of COVID-19 began to emerge from China in late January and medical literature described the lung injury and inflammatory damage, Atyr executives took notice.
Thats when it started to occur to us we may have a hyperacute environment going on here, Shukla said.
ATYR-1923, a modulator of neuropilin-2, down-regulates T-cell responses and disrupts the inflammatory cytokine and chemokine signaling found in severe COVID-19 patients. In several animal models of immune-mediated acute lung injury, it has improved lung function and reduced inflammation and fibrosis.
One key differentiator of our product is it interfaces directly with the immune cells and not the immune markers, Shukla said, adding that a number of monoclonal antibodies currently tested focus solely on either interleukin-6, interleukin-2, tumor necrosis factor (TNF) or granulocyte macrophage colony-stimulating factor (GM-CSF), but all are very important inflammatory biomarkers and by turning them down, we reset the immune balance.
The randomized, double-blind, placebo-controlled phase II trial will enroll 30 confirmed COVID-19 patients at up to 10 centers in the U.S. They will receive either a placebo or a single intravenous dose (1 mg/kg or 3 mg/kg) with the aim of demonstrating safety and preliminary efficacy.
Calcimedicas CRAC channel inhibitor
Another company focused on severe respiratory complications of COVID-19 is La Jolla, Calif.-based Calcimedica Inc., which started a phase IIa study with its small-molecule calcium release-activated calcium (CRAC) channel inhibitor, CM-4620-injectable emulsion (IE), in patients with severe pneumonia who are at risk for ARDS. The company received a Study May Proceed letter from the FDA earlier this month and the trial began April 8.
The four-person company was in the process of starting a phase IIb study in acute pancreatitis, the mortality of which is due to lung injury and ARDS.
When the pandemic started, said Sudarshan Hebbar, privately held Calcimedicas chief medical officer, we obviously shifted focus immediately to try to put the IND through to the FDA. We had an IND in at the pulmonary division and were told to submit an IND to the antiviral division.
The phase IIb in acute pancreatitis was put on hold and the COVID-19 trial is expected to be completed in July. Data thus far has shown CM-4620-IE to be safe with potential efficacy in patients with hypoxemia secondary to systemic inflammatory response syndrome from acute pancreatitis.
Our goal when we talked to the FDA was we wanted to prevent people from going on ventilators, Hebbar told BioWorld. Thats where we see the real need is.
CM-4620-IE prevents the increase of intracellular calcium from CRAC channel overactivation and alleviates pulmonary endothelial damage and the cytokine storm in COVID-19 patients. It inhibits the Icrac pathway in human T cells, blocking IL-2 and TNFa, and has been shown to reduce neutrophil activation. Having three different integrated mechanisms of action differentiates the candidate from other agents, as does its lack of long-term immunosuppression, Hebbar said.
We know that once you stop the infusion of our drug, within 24 or 36 hours the immune system returns back to normal, he added.
An open-label phase II trial will enroll 60 patients on low-flow oxygen with severe COVID-19 pneumonia, 40 of whom will receive CM-4620-IE plus standard of care, while 20 receive standard of care alone. The trial was expanded to include a second arm of 60 patients on high-flow oxygen. The first patients enrolled were at Regions Hospital in St. Paul, Minn., with additional patients enrolled at Henry Ford Hospital in Detroit and seven other sites.
Next steps, other options
Both Shukla and Hebbar credited the FDA for its swift pace in helping the companies get their internally funded trials set to begin. The agency has shown enthusiasm for new therapies, while it continues to provide the emergency use authorization pathway for approved and repurposed drugs. Assuming positive results in the phase II trials, both Atyrs and Calcimedicas candidates would then move to pivotal trials.
Other candidates for COVID-19 respiratory complications include La Jolla, Calif.-based Inmune Bio Inc.s dominant-negative TNF inhibitor; Cambridge, U.K.-based Astrazeneca plcs BTK inhibitor Calquence (acalabrutinib); Vancouver, Wash.-based Cytodyn Inc.s CCR5 antagonist PRO-140 (leronlimab); Hemel Hempstead, U.K.-based Eusa Pharma Inc.s siltuximab; and Foster City, Calif.-based Gilead Sciences Inc.s antiviral remdesivir.
Inmune announced its phase II trial on April 20 and said it was working with regulatory authorities and clinical sites to get started quickly. As of April 15, the first of about 390 patients with severe infection were dosed in a phase IIb/III study with PRO-140. A phase II study with siltuximab began April 15 in 200 patients with COVID-19 pneumonia in an effort to prevent progression and admission to an ICU. Remdesivir, which is in several phase III trials, showed cumulative incidence of clinical improvement of 84% in 53 hospitalized patients with severe complications who were treated on a compassionate use basis. And Astrazenecas acalabrutinib began the Calavi phase II trial in 428 patients in mid-April.
This is the fastest launch of any clinical trial in the history of Astrazeneca, said Jose Baselga, the companys executive vice president of oncology R&D.
Also working on therapies for respiratory complications are Tel Aviv, Israel-based Redhill Biopharma Ltd., which filed an IND to start a U.S. clinical trial for opaganib, its oral small-molecule sphingosine kinase-2 selective inhibitor, and El Segundo, Calif.-based Nantkwest Inc. and Culver City, Calif.-based Immunitybio Inc., which are developing a mesenchymal stem cell therapy specifically for patients with ARDS due to severe COVID-19.
The World Health Organization reported a total of 2.95 million confirmed infections and 202,597 deaths on April 28. While that puts the death rate at about 6.9%, a true figure is expected to be much lower, assuming that a more accurate count of asymptomatic individuals and others infected will eventually be made.
I think were in some desperate need for some help here until we get a good vaccine, Shukla said, adding that no single solution will be enough to beat COVID-19. Were going to need a toolkit.
Read the original here:
- Impacts of the COVID-19-Mesenchymal Stem Cells Market Size Current and Future Industry Trends, 2020-2028 - 3rd Watch News - July 4th, 2020
- IHS Pets: Bringing Cell And Gene Therapy To Cats, Dogs & Horses - Anti Aging News - July 4th, 2020
- Calidi Biotherapeutics Announces Appointment of Jim Schoeneck, Accomplished Biotech Executive, to Board of Directors - StreetInsider.com - July 4th, 2020
- Biology of Mesenchymal Stem Cells | Bentham Science - July 1st, 2020
- Mesenchymal Stem Cells and Skeletal Regeneration ... - July 1st, 2020
- Amniotic Membranes Market is Projected to Expand at a CAGR of ~10% From 2019 to 2027 - Science Examiner - July 1st, 2020
- Mesenchymal Stem Cells Market 2020 Projections, Growth Opportunities, Trends, Companies Strategies and Forecast 2024 | Lonza, Thermo Fisher,... - July 1st, 2020
- Citius Receives FDA Response on Pre-Investigational New Drug (PIND) Application for its Induced Mesenchymal Stem Cells (iMSCs) to Treat Acute... - June 30th, 2020
- Amniotic Membrane Market by Product, Application and Forecast to 2027 TMR - 3rd Watch News - June 30th, 2020
- Human Primary Cells Market Global ? How the Market has witnessed Substantial Growth in recent years? - 3rd Watch News - June 30th, 2020
- Exosome Therapeutic Market Size, 2020-New Technological Change Helping Market, Application, Driver, - PharmiWeb.com - June 30th, 2020
- Research on Human Mesenchymal Stem Cells (hMSC) Market (impact of COVID-19) with Top Players: PromoCell, ThermoFisher, KURABO, Merck, and - 3rd Watch... - June 23rd, 2020
- Stem Cell Manufacturing Market 2020 Global Size, Share, Progress Insight, Share, Trends, Industry Key Players-Merck Group, Becton, Dickinson And... - June 23rd, 2020
- Efforts at coronavirus vaccines and treatments abound in the Bay Area - San Francisco Chronicle - June 23rd, 2020
- Exosome Therapeutic Market 2020 Opportunity Ahead of Earnings with evox THERAPEUTICS, EXOCOBIO, Exopharm, AEGLE Therapeutics, United Therapeutics... - June 23rd, 2020
- Mesenchymal Stem Cells Market to Witness Robust Expansion throughout the Forecast 2020 - Owned - June 19th, 2020
- Worldwide Stem Cell Therapy Industry to 2027 - Growth in the Global Healthcare Market Presents Opportunities - PRNewswire - June 19th, 2020
- Human Primary Cells Market Regional Analysis, key Drivers and Restraints, by Product, Top Players and Forecast Analysis 2020-2026 - Bulletin Line - June 19th, 2020
- Impressive Trends and Future Scope of Mesenchymal Stem Cells Market - 3rd Watch News - June 14th, 2020
- Regenerative Therapy Options for Horses With Osteoarthritis - TheHorse.com - June 14th, 2020
- MSC Therapy for Acute Respiratory Distress Syndrome; It's Time to Accelerate Clinical Trials for COVID-19 Patients in Need - P&T Community - June 8th, 2020
- COVID-19 Therapeutics: The Leading Contenders - Seeking Alpha - June 6th, 2020
- Global Mesenchymal Stem Cells Market Expected to Witness the Highest Growth during 2020-2026 - Jewish Life News - June 6th, 2020
- AgeX Therapeutics, ImStem Biotechnology sign non-binding letter of intent regarding investigational MSC candidate IMS001 for Covid-19 - Pharmaceutical... - June 3rd, 2020
- AgeX Therapeutics and ImStem Biotechnology Sign Non-Binding Letter of Intent Regarding Investigational MSC Candidate IMS001 for COVID-19 and Other... - June 3rd, 2020
- Mesenchymal Stem Cells Market trends by manufacturers, states, type and application, forecast to 2019 2027 - WhaTech Technology and Markets News - June 3rd, 2020
- Human Mesenchymal Stem Cells (hMSC) Market investigated in the latest research - WhaTech Technology and Markets News - June 3rd, 2020
- Stem Cell Treatments Market 2020- Analysis And In-Depth Research On Market Size, Trends, Emerging Growth Factors And Forecast To 2026 - 3rd Watch News - June 3rd, 2020
- MSC Therapy for Acute Respiratory Distress Syndrome; It's Time to Accelerate Clinical Trials for COVID-19 Patients in Need - PRNewswire - June 3rd, 2020
- Global Stem Cell Characterization Kits Market : Analysis and In-depth Study on Market Size Trends, Emerging Growth Factors and Forecasts to 2029 - The... - June 3rd, 2020
- Mesoblast (ASX:MSB) reveals promising trial results for lung disease treatment - The Market Herald - June 3rd, 2020
- Longeveron Announces Japanese Approval of Clinical Trial for Treatment of Aging Frailty With Longeveron's Stem Cells | DNA RNA and Cells | News... - June 2nd, 2020
- Stem Cell Cartilage Regeneration Market Overview By Growing Demands, Trends And Business Opportunities 2020 To 2027 - Cole of Duty - June 2nd, 2020
- Photoaged Skin Therapy with Adipose-Derived Stem Cells - MedicalResearch.com - June 2nd, 2020
- Intravenously Delivered Mesenchymal Stem Cells Prevent Microvascular Obstruction Formation After Myocardial Ischemia/Reperfusion Injury - DocWire News - June 2nd, 2020
- COVID-19: Responding to the business impacts of Mesenchymal Stem Cells Market Trends Analysis, Top Manufacturers, Shares, Growth Opportunities,... - June 2nd, 2020
- Mesenchymal Stem Cells Market Research Report 2020: Key Players, Applications, Drivers, Trends and Forecast to 2026 - WaterCloud News - June 2nd, 2020
- Global Human Primary Cells Market 2020 by Manufacturers, Countries, Type and Application, Forecast to 2025 - Bandera County Courier - June 2nd, 2020
- Could Cell Therapy Target the Symptoms of Severe... - Labiotech.eu - May 25th, 2020
- The Week Ahead In Biotech: ASCO Presentations In The Spotlight - Yahoo Finance - May 25th, 2020
- In situ repair abilities of human umbilical cordderived mesenchymal stem cells and autocrosslinked hyaluronic acid gel complex in rhesus monkeys with... - May 23rd, 2020
- We now have a special power to kill the virus - Bangalore Mirror - May 23rd, 2020
- Cells for Cells and Austrianova announce publication on novel method to produce stem cell exosomes - BioSpace - May 23rd, 2020
- Clinical Trial Shows Topical Stem Cell Treatment Leads to Hair Regrowth in Common Type of Baldness - Technology Networks - May 19th, 2020
- Unproven stem cell products are being peddled as COVID-19 'therapies,' U of M researcher reports - MinnPost - May 19th, 2020
- NantKwest Announces FDA Authorization of IND Application for Mesenchymal Stem Cell Product for the Treatment of Severe COVID-19 Patients - Business... - May 19th, 2020
- Can stem cell therapy help - Greater Kashmir - May 19th, 2020
- Be The Match BioTherapies and NantKwest Announce Collaboration to Accelerate Development of Cell Therapy to Prevent COVID-19 Deaths - Business Wire - May 19th, 2020
- Cell Freezing Media for Cell Therapy Market to Exhibit Impressive Growth of CAG - News by aeresearch - May 19th, 2020
- Latest Study explores the Microencapsulated Omega3 Powder Market Witness Highest Growth in near future - AlgosOnline - May 16th, 2020
- Coronavirus Diaries: A Covid scientist on the hunt for a cure, and a GP on what doctors need to learn - Financial Times - May 16th, 2020
- Umbilical Cord Stem Cell Therapy to Be Assessed in Severe COVID-19 - Monthly Prescribing Reference - May 16th, 2020
- Umbilical cord stem cells have the potential to treat COVID-19 - Open Access Government - May 14th, 2020
- Global Mesenchymal Stem Cells Market 2020 with (Covid-19) Impact Research by Top Manufacturers, Industry Growth, Regional Analysis and Forecast by... - May 14th, 2020
- Citius Announces Data on NoveCite Mesenchymal Stem Cells (NC-MSCs) to be Presented at the American Society of Gene and Cell Therapy (ASGCT) Annual... - May 14th, 2020
- The Latest Technological Innovations in Orthopedic Surgery 2020 Technology - IMC Grupo - May 14th, 2020
- AMC to use stem cell therapy in treating graft-versus-host disease - Korea Biomedical Review - May 7th, 2020
- 5 Stem Cell Companies Racing Towards COVID-19 ARDS Therapy - Seeking Alpha - May 7th, 2020
- Characterization and Immunomodulation of Canine Amniotic Membrane Stem | SCCAA - Dove Medical Press - May 7th, 2020
- FDA Approves AstraZeneca's Farxiga for Heart Failure in Adults with Reduced Ejection Fraction - BioSpace - May 7th, 2020
- DIABETES RESEARCH INSTITUTE FOUNDATION RECEIVES $3 MILLION GIFT FROM NORTH AMERICA'S BUILDING TRADES UNIONS TO FUND CELL THERAPY FOR COVID-19 -... - May 7th, 2020
- Pass the MUST-ARDS: Athersys starts pivotal study for stem cells to treat COVID-19-induced ARDS - BioWorld Online - May 7th, 2020
- Mesenchymal Stem Cell - an overview | ScienceDirect Topics - May 5th, 2020
- Frontiers | Senescence in Mesenchymal Stem Cells ... - May 5th, 2020
- Investigational new drug may be beneficial in treating severe COVID-19 - BioNews - May 5th, 2020
- BioCardia Announces Positive Preclinical Results Supporting Investigational New Drug Application for Anti-Inflammatory Cell Therapy in Heart Failure -... - May 5th, 2020
- Mesenchymal Stem Cells | Properties, Process, Functions ... - May 5th, 2020
- Pipeline: Immunotherapies and Other Investigational Therapies for COVID-19 - MPR - Monthly Prescribing Reference - May 5th, 2020
- Cell Freezing Media for Cell Therapy Market Expected to Witness the Highest Grow - News.MarketSizeForecasters.com - May 5th, 2020
- Targeted pathological collagen delivery of sustained-release rapamycin to prevent heterotopic ossification - Science Advances - April 30th, 2020
- EMA warns against unproven therapies - English - Agenzia ANSA - April 30th, 2020
- US FDA Allows Trial to Proceed for Retrotopes RT001 in the Treatment of Progressive SupraNuclear Palsy (PSP) - Yahoo Finance - April 28th, 2020
- Stem cell therapy shows 83% survival of Coronavirus patients on ventilators - International Business Times, Singapore Edition - April 26th, 2020
- Researcher says stem cell activation could lie at root of health effects of many natural products - NutraIngredients-usa.com - April 26th, 2020
- Mesenchymal Stem Cells: The 'Other' Bone Marrow Stem Cells - April 24th, 2020
- The Dual Nature of Mesenchymal Stem Cells (MSCs): Yin and ... - April 24th, 2020
- Mesenchymal - Stemcell Technologies - April 24th, 2020
- Stem Cells Market Outlook with a Focus on Clinical Therapies 2020-2030: Types of Stem Cells, Route of Administration, Therapeutic Areas, End-users,... - April 24th, 2020
- Mesenchymal stem cells as a potential treatment for ... - April 24th, 2020
- Researchers turn to stem cells in COVID-19 battle How does the treatment work and does it pose any risk? - Times Now - April 24th, 2020