The promising COVID therapy for respiratory failure few have heard of, but will soon - NeuroRx and Relief Therapeutics RLF-100 (Aviptadil)

RELIEF THERAPEUTICS 4 CLINICAL TRIALS AS OF NOW:

(1) Clinical Trial NCT04311697 – IV Trial

For intravenous RLF-100 administered to patients in ICUs with respiratory failure.
Seeks to enroll 144 patients.
Currently in “Phase 2b/3”, meaning it will evaluate both dosing and efficacy.
First interim review was held at 30 patients, which determined RLF-100 is safe for human use.
Second interim review will be held at 102 patients with a determination to: 1) stop the trial because the drug is dangerous, 2) stop the trial because the drug shows no effect, 3) continue the trial because results look good, 4) stop the trial because the drug is proven.
Patient #102 was enrolled on 9/30/2020; therefore once that patient completes their trial (28 days later), the Data Monitoring Committee (DMC) will review results and submit a recommendation to the FDA.
Doctor (and Congressman) Andy Harris is 1 of 3 experts on the DMC.

First Interim Review: https://relieftherapeutics.com/neurorx-and-relief-therapeutics-announce-data-monitoring-committee-determination-to-continue-phase-2-3-trial-of-rlf-100-for-critical-covid-19/

(2) Clinical Trial NCT04453839 – EAP Trial

This EAP (Expanded Access Protocol) trial allows RLF-100 to be used as a last-resort for patients too sick for regular trial participation (commonly referred to as "compassionate use").
EAP is NOT the same as EUA (Emergency Use Authorization) – see clarification below
Early EAP results were released in a “pre-print” document for patients considered to be “the sickest of the sick” (ICU, ventilator, ECMO patients).
Results: For patients who received RLF-100, 19 out of 21 patients survived, where only about 6 were expected to survive.

Initial EAP Results Pre-print: https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3665228

(3) Clinical Trial NCT04360096 – Treatment Inhaler

This trial is a study of 288 patients in the United States to test an inhaler-version of RLF-100, intended to ultimately be used for in-home nebulizer treatments.
Dr. Javitt: “We expect that half the people we enroll in our inhaled study are going to be people who are outpatients.”
Current estimated completion in 2020

(4) Clinical Trial NCT04536350 – Preventative Inhaler

This trial is a study of 80 patients in Switzerland to test an inhaler-version of RLF-100 as a “preventative treatment”.
Current estimated completion in December 2021

The 4 studies for Aviptadil can be found here: https://clinicaltrials.gov/ct2/results?term=Aviptadil&draw=2&rank=1#rowId0

EXPLAINATIONS:

EAP = Expanded Access Protocol – currently approved
EUA = Emergency Use Authorization – submitted application to FDA
EAP allows RLF-100 to be used as a last-resort for patients too sick for regular trial participation.
Qualifying for EAP is limited: the patient must be located at one of the few clinical trial hospitals, or transfer to a participating hospital, or have the hospital attempt to qualify for the drug.
Due to EAP limitations, NeuroRX recently applied for EUA and is awaiting FDA approval.
EUA allows experimental drug use during public health emergencies. Qualifications are that the drug must be safe and “may” be effective.
If approved, EUA will allow RLF-100 to be used at all US hospitals, as a last resort when all other approved treatments have failed.
EUA approval is not necessarily dependent upon trial completion or interim reviews, unless FDA subsequently requests more data.
Currently there are only 2 other EUA approved therapeutics: Remdesivir and Convalescent Plasma

A similar VIP drug was just pulled for Covid-19 study.

Two key points on this first:

1. PhaseBio Pharmaceuticals' Pemziviptadil binds to the VPAC2 receptor in the blood vessels, whereas Aviptadil targets the VCAP1 receptor in the lung.

2. PhasBio voluntarily pulled their study after the FDA made a suggestion (not a rejection) that, essentially, their study was too small. Point being, the FDA did NOT reject a synthetic VIP for Covid treatment. However, the difference in mode of action of the two different VIP's would likely have become much clearer the longer the PhasBio version was studied.

Dr. Javitt from NeuroRX describes the key differences between Aviptadil (VCAP2 receptor) and Pemziviptadil (VCAP1 receptor): Discussion with Dr. Javitt: RLF-100 Updates

The PhaseBio press release:

PhaseBio Provides Pemziviptadil (PB1046) Program Update
In response to the medical community’s rapidly evolving understanding of COVID-19 disease progression and approaches to treatment, PhaseBio recently submitted a revised VANGARD trial protocol and received feedback from the FDA regarding the regulatory and development path in COVID-related ARDS. For pemziviptadil use in hospitalized COVID-19 patients at high risk for rapid clinical deterioration and ARDS, the FDA highlighted the likely need for additional clinical trials with sufficient sample size to adequately assess mortality risk. Based on this feedback, PhaseBio determined that it would be unlikely that the 70 patients targeted for enrollment in each of the VANGARD trial’s treatment arms would be sufficient in size to adequately evaluate mortality and that at least one additional clinical trial with a mortality endpoint, which would require significantly more patients, would be required for approval of pemziviptadil for use in patients diagnosed with COVID-19.
...
The ongoing Phase 2b trial of pemziviptadil in patients with PAH, named the VIP Trial (Vasoactive Intestinal Peptide in adult patients with pulmonary arterial hypertension) is expected to quickly resume enrollment after a pause related to the impacts of the COVID-19 pandemic and re-prioritization of drug supply to the VANGARD trial.

Key point to remember, these VIP drugs work differently by targeting different receptors in the body.

Aviptadil is still on track.

COVID Coronavirus sets Relief Therapeutics (OTC:RLFTF) up for astronomical success OCTOBER 23, 2020

"The COVID coronavirus is setting this little known company up for great success. Shares of Relief Therapeutics (OTC:RLFTF) is still relatively low, so investors still have a chance of getting in on the ground floor. The company recently updated their website which provides more information about their business and their pipeline.

RLF-100™ has a 20-year history of safe use in humans in multiple human trials for sarcoidosis, pulmonary fibrosis, asthma/allergy, and pulmonary hypertension. It has been shown in more than 100 peer-reviewed studies to have potent anti-inflammatory/anti-cytokine activity in animal models of respiratory distress, acute lung injury and inflammation.

RLF-100™ is currently in clinical testing for acute lung injury (ALI) associated with the SARS-CoV-2 virus (COVID-19).

Relief devised a swift plan of action to respond to one of the largest healthcare disasters our time by rapidly advancing RLF-100™ towards approval in COVID-19-induced lung injury. Through its multimodal mechanism of action, RLF-100™ may uniquely target the pathways attacked by the SARS-CoV-2 virus (COVID-19), preventing acute lung injury (ALI).

COVID-19-related death is primarily caused by respiratory failure. Before this acute phase, however, there is evidence of early viral infection of the alveolar type 2 cells. These cells are known to have angiotensin converting enzyme 2 (ACE2) receptors at high levels, which serve as the route of entry for the SARS-CoV-2 into the cells. Coronaviruses are shown to replicate in alveolar type 2 cells, but not in the more numerous type 1 cells. These same type 2 alveolar cells have high concentrations of VIP receptors on their cell surfaces giving rise to the hypothesis that VIP could specifically protect these cells from injury.

Injury to the type 2 alveolar cells is an increasingly plausible mechanism of COVID-19 disease progression. (Mason 2020). These specialized cells replenish the more common type 1 cells that line the lungs. More importantly, type 2 cells manufacture surfactant that coats the lung and are essential for oxygen exchange. Other than RLF-100™, no currently proposed treatments for COVID-19 specifically target these vulnerable type 2 cells.

RLF-100™ specifically targets alveolar type 2 (AT2) cells in the lung. The company is objective in establishing RLF-100™ as the standard of care for intensive care units (ICUs) in acute as well as chronic contexts to prevent and cure respiratory failure and its complications.

RLF-100™ will prevent lung fibrosis and pulmonary sarcoidosis based on their recent studies."

NeuroRx and Relief Therapeutics announce continuation of RLF-100™ trial for treatment of COVID-19 Respiratory Failure: Trial is on track to complete enrollment in 2020

RADNOR, Pa. and GENEVA, Nov. 5, 2020 /PRNewswire/ -- NeuroRx, Inc. and Relief Therapeutics Holdings AG (SIX:RLF,OTCBB:RLFTF) ("Relief") announced that the independent Data Monitoring Committee (DMC) met yesterday and voted unanimously that NCT 04311697 should continue as planned to its full enrollment of 165 patients. Specifically, the committee identified no safety concerns and viewed the study as capable of reaching its prespecified endpoint (i.e. no finding of futility) in potentially proving that RLF-100™ (aviptadil) is superior to placebo in achieving recovery from Respiratory Failure in patients with Critical COVID-19 at a statistically significant level.

...

The review by the DMC was based on data from 102 patients who were randomly assigned to intravenous RLF-100™ vs. placebo and who have completed 28 days or more of observation. All patients were hospitalized in intensive care units with respiratory failure treated by mechanical ventilation, non-invasive ventilation, or high-flow nasal oxygen. So far, 133 patients have been treated in this protocol. At current rates of enrollment (which may change as infection rates change) the study is expected to complete enrollment by mid-December and yield top-line data in January 2021.

Although the study remains blinded, the randomized data overall show that there have been no drug-related Serious Adverse Events to date. Similarly, no drug-related adverse events were seen in the open label study of the ongoing Expanded Access Protocol.

...

NeuroRx and Relief announce initial successful results from expanded access use of RLF-100™ (aviptadil) in patients with Critical COVID-19 and Severe Comorbidity: 72% survival seen in ICU patients

RADNOR, Pa. and GENEVA, Nov. 24, 2020 /PRNewswire/ -- NeuroRx, Inc., and Relief AG (SIX: RLF,OTCQB: RLFTF), announce that more than 175 patients with Critical COVID-19 and Respiratory Failure who also have a severe comorbidity have now been entered into an Expanded Access Protocol (EAP) with RLF-100TM in the United States.

All patients had severe comorbidities (such as organ transplant, recent heart attack, and cancer) that rendered them ineligible for the ongoing randomized, controlled phase 2b/3 trial being conducted to ascertain safety and efficacy of RLF-100™, and all patients were deteriorating despite treatment with approved therapies for COVID-19 (see www.clinicaltrials.gov NCT 04311697). Of the 90 patients who have so far reached 28 days of follow-up, 72% survived to day 28.

As previously reported by Youssef and coworkers (http://dx.doi.org/10.2139/ssrn.3665228), at Houston Methodist Hospital, 21 patients treated with RLF-100™ under the EAP were compared to 24 control patients treated in the same setting. Only 27% of the control patients, all treated with best available intensive care unit (ICU) Standard of Care, survived to day 28. The survival rate with RLF-100TM reported today is comparable to that seen among the open-label patients treated with RLF-100™ by Youssef et al. Despite advancements in treating COVID-19, survival for the patients at highest risk due to severe comorbidities has remained dismal in the absence of an effective therapy.

Notably, in the EAP, no drug-related Serious Adverse Events have been reported to date among these patients nor the 160 patients randomized to RLF-100™ vs. placebo in the U.S. phase 2b/3 clinical trial currently underway. Thus, from a risk/benefit perspective, while the benefit of RLF-100TM has not yet been proven in a randomized prospective trial, no serious risk has been identified so far.

...

https://www.prnewswire.com/news-releases/neurorx-and-relief-announce-initial-successful-results-from-expanded-access-use-of-rlf-100-aviptadil-in-patients-with-critical-covid-19-and-severe-comorbidity-72-survival-seen-in-icu-patients-301179820.html

Update on Aviptadil (RLF-100) know called ZYESAMI

NeuroRx and Relief Therapeutics Report Initial Phase 2b/3 Study Results Demonstrating Significant Benefit of ZYESAMI™ in Reducing Hospital Stay Among Patients with Respiratory Failure due to Critical COVID-19

RADNOR, Pa. and GENEVA, Feb. 9, 2021 /PRNewswire/ -- NeuroRx, Inc.. and Relief Therapeutics Holdings AG (SIX:RLF; OTCQB: RLFTF) today reported preliminary results from the Phase 2b/3 trial of ZYESAMI™ (aviptadil, previously RLF-100) in patients with respiratory failure due to Critical COVID-19. The study showed that patients who were treated with the maximal standard of care plus ZYESAMI benefited significantly from the treatment, compared to those treated with placebo plus maximal standard of care. If authorized for use, ZYESAMI would be the first drug indicated specifically for COVID-19 patients who are critically ill with respiratory failure.

...

"The study has *not yet determined* results for the stated primary endpoint of recovery from respiratory failure."

Preliminary Study Results:

Primary endpoint = resolution of respiratory failure within 28 days after treatment started. [On-going assessment].
Secondary endpoints = (A) patient survival [Success], (B) time to ICU discharge [Success], (C) time to hospital discharge [Success], (D) time to return to NIAID score of 6-8 [Data unavailable], and (E) safety [Success].
Standard of care (SOC) treatments including Remdesivir, anti-cytokine drugs, steroids, and anticoagulants. A total of 138 patients (91 ZYESAMI, 47 SOC) survived through Day 28. Ninety-six patients (65 ZYESAMI, 31 SOC) were discharged from the hospital by Day 28.
The first demonstration of clinically and statistically-significant benefit by any therapeutic agent in patients with COVID-19 respiratory failure in a randomized, double-blind, prospective trial.

Upcoming:

Will discuss with FDA submission of an Emergency Use Authorization (EUA).
Launched a phase 2/3 trial to explore its inhaled use in patients who are not yet in respiratory failure.
Further study of ZYESAMI's role in critical COVID-19 will be conducted under the BARDA and DOD Medical Countermeasures-funded I-SPY trial.
Signed a clinical trial agreement with another federal program the details of which will be announced shortly.
Will report on day 60 survival.

Great news!

NeuroRx Announces that ZYESAMI™ (Aviptadil) has Successfully Demonstrated 10-Day Accelerated Recovery from Respiratory Failure in Critically Ill Patients with Covid-19 Treated with High Flow Nasal Oxygen at 28-Day Interim Endpoint
NeuroRx to File for Emergency Use Authorization in This Patient Population if Positive Results Continue to be Demonstrated at Day-60 Endpoint in Line with FDA's New Guidance
NEWS PROVIDED BY NeuroRx Feb 23, 2021, 13:11 ET

RADNOR, Pa., Feb. 23, 2021 /PRNewswire/ -- NeuroRx, Inc. announced today that the Phase 2b/3 trial* of ZYESAMI™ (aviptadil, previously RLF-100™) for the treatment of Respiratory Failure in critically ill patients with Covid-19 has demonstrated multidimensional benefit around its prespecified primary endpoint of Recovery from Respiratory Failure with discharge from hospital and ICU (without relapse) by day 28 in patients with critical Covid-19 who were treated with High Flow Nasal Oxygen. Although not envisioned at the start of the clinical trial, High Flow Nasal Oxygen has become the predominant form of treatment in Covid-19 respiratory failure, with mechanical ventilation reserved for those whose blood oxygen levels cannot be maintained on this less invasive modality. The trial was conducted at 10 U.S. hospitals under the direction of NeuroRx in collaboration with RELIEF THERAPEUTICS Holding AG (SIX: RLF;OTCQB: RLFTF). NeuroRx has signed an agreement to complete a business combination with Big Rock Partners Acquisition Corporation (NASDAQ:BRPA).

The clinical trial was originally approved as a 28-day study at FDA's direction. In December, NeuroRx added a 60-day endpoint based on the recognition that the traditional 28-day endpoint adopted in the 1990s for trials in Acute Respiratory Distress Syndrome is not appropriate for critically ill patients with Covid-19, who are frequently maintained in the ICU with advanced technologies well beyond this time point. NeuroRx and other clinical trial sponsors alerted FDA to this trend and yesterday the FDA published formal guidance† changing the required time for measuring the prespecified endpoint of "alive and free of respiratory failure" in critically ill patients to 60 days. Interim data are being reported because they were unblinded as per the original protocol and the last patient in the trial reached day 60 yesterday. Therefore, study conduct cannot be adversely influenced by release of these interim findings.

At 28 days, patients treated with ZYESAMI™ demonstrate 35% higher likelihood of recovery from respiratory failure with continued survival compared to patients treated with placebo (Hazard Ratio 1.53; P=.08). In tertiary care hospitals, ZYESAMI-treated patients were 46% more likely to recover and return home before day 28 (Hazard Ratio controlling for age and severity 1.84; P=.058). Should these trends continue through day 60, they have the potential to reach statistical significance. At day 28, a highly significant 10-day difference in median time to recovery and hospital discharge has emerged in ZYESAMI-treated patients compared to those treated with placebo (P<.006).

Should the above trends continue through day 60, NeuroRx anticipates filing a request for Emergency Use Authorization in this population of critically ill patients (i.e. those on High Flow Nasal Oxygen) who have exhausted all currently approved treatments. FDA decisions implement a benefit/risk framework. NeuroRx previously announced the high degree of safety observed with use of ZYESAMI. This safety has continued to be documented in the more than 300 additional patients treated under the Expanded Access Protocol and in patients who have filed requests under the federal Right to Try act.

Yesterday's guidance emphasizes the importance of analyzing patient outcomes by treatment subgroup and, in this case, the study did not recruit enough patients treated with mechanical ventilation to confirm the benefit seen in open-label studies. In the seven months that have elapsed since the trial began, mechanical ventilation has gone from first-line therapy to treatment of last resort for patients with Covid-19. Recognizing this, NeuroRx signed clinical trial agreements with the I-SPY clinical trial platform and the National Institutes of Health under which ZYESAMI will continue to be evaluated in patients who require mechanical ventilation.

The study's principal investigators, Dushyantha Jayaweera, M.D., FACP (University of Miami), Professors J. Georges Youssef, M.D. (Houston Methodist Hospital), and Richard Lee, M.D. (University of California, Irvine), commented, "We are excited to report that ZYESAMI demonstrates a highly significant reduction in time to recovery compared to patients treated with placebo in those treated with High Flow Nasal Oxygen, together with increased likelihood of recovery and excellent safety. We look forward to learning whether this benefit can also be shown for patients treated with other stages of Covid-19 with inhaled forms of ZYESAMI. We look forward to working with the sponsor to secure emergency use authorization for ZYESAMI in this population of patients."

Jonathan C. Javitt, M.D., M.P.H., CEO of NeuroRx, added, "We look forward to reporting the final 60-day efficacy data shortly. We are indebted to the researchers, patients, and families who have helped us demonstrate this meaningful clinical benefit for ZYESAMI. We are honored to name the drug in honor of the late Prof. Sami Said, who discovered its active ingredient, VIP. Additional efficacy data on patients who require mechanical ventilation will be obtained from ongoing research supported by BARDA and the National Institutes of Health, in addition to our newly initiated study of inhaled use ZYESAMI in hospitalized patients who have not yet developed respiratory failure."

BRPA/Relief Therapeutics is almost certainly to be reviewed by the European Union for EMA based on evaluation of 57 therapeutics....only 8 of which have Phase 3 results to qualify them....and only 3 of which are true competition. Full breakdown of all Data with tables and descriptions

The EU has posted a consensus document stating that they will narrow down their selection to 10 drugs from their list of 57 current COVID therapeutics....with multiple drugs to be approved this year.

“The Strategy includes clear actions and targets, including authorizing three new therapeutics to treat COVID-19 by October 2021 and possibly two more by end of the year.”

AND

“The Commission will draw up a portfolio of 10 potential COVID-19 therapeutics and by June 2021, identify the five most promising ones. It will organize matchmaking events for industrial actors involved in therapeutics to ensure enough production capacity and swift manufacturing. New authorizations, rolling reviews and joint procurement contracts will be up and running before the end of the year.”

https://ec.europa.eu/commission/presscorner/detail/en/ip_21_2201?fbclid=IwAR2YUzo8Lu77hdl6eMR71QI5Q0c7HVjo55yfTbTZLVtT1szGQ2thgXV8P4A

The list of 57 drugs can be found here:

https://www.ema.europa.eu/en/human-regulatory/overview/public-health-threats/coronavirus-disease-covid-19/treatments-vaccines/treatments-covid-19/covid-19-treatments-research-development

Of this list, only 36 are clinical, the rest are still in phase 1 development and would not be ready for a 2021 approval/use.

Of the 36 clinical drugs, only 13 have completed phase 3 trials. Of those 13, 5 showed no benefit. That leaves 8 drugs. Of those 8, 7 have had statistically significant results and 1 is pending its phase 3 results. 2 of the 7 have EUAs (remdesavir and Baricitinib). Remdesavir already has an EMA.

That means that Relief Therapeutics has 6 competitors, one of which is pending results that may or may not be significant. This means we are almost certainly getting on the EMA list of 10 for consideration. RLF is by far the most effective and cheapest on the final list of 7 competitors.

Our competitors are: Tocilizumab, Sarilumab, Gimsilumab (results pending), Colchicine, Baricitinib, VIR-7832.

Of these competitors, colchine's data was crappy and Tocilizumab showed conflicting results.

Baricitinib is already under consideration by the EMA and will almost certainly be authorized.

That means, Sarilumab, Gimsilumab and VIR-7832 are our only true competition. These are all expensive monoclonals. RLF is the only non-MAB in the bunch.

https://www.reddit.com/r/ReliefTherapeutics/comments/n744kw/brparelief_therapeutics_is_almost_certainly_to_be/

Write-up on the results from trial NCT04311697

Increased Recovery and Survival in Patients With COVID-19 Respiratory Failure Following Treatment with Aviptadil: Report #1 of the ZYESAMI COVID-19 Research Group

9 Pages Posted: 11 May 2021

Jihad G. Youssef
Houston Methodist Research Institute

Richard Lee
University of California, Irvine

Jonathan Javitt
Johns Hopkins School of Medicine; Potomac Institute for Policy Studies; NeuroRx

Philip Lavin
Boston Biostatistical Research Foundation

Rainer Lenhardt
University of Louisville School of Medicine

David J. Park
Providence St. Jude Medical Center/St. Joseph Health Care

Javier Perez Fernandez
Medical Director, Critical Care

Melvin Morganroth
Oregon Clinic

Dushyantha Jayaweera
University of Miami - Miller School of Medicine

Date Written: April 23, 2021

Abstract

Background: There is currently no approved drug for critically ill patients with respiratory failure caused by COVID-19. Vasoactive Intestinal Peptide (VIP) blocks replication of the SARS-CoV-2 virus in alveolar type II cells, inhibits cytokine synthesis, prevents cytopathy, and upregulates surfactant production.

Methods: A multicenter, randomized, placebo-controlled trial in 196 patients with PCR+ COVID-19 receiving intensive care at 10 U.S. hospitals – 6 tertiary care and 4 regional hospitals -- to determine whether intravenous aviptadil (synthetic VIP) is superior to placebo in achieving recovery from respiratory failure and survival at 60 days post treatment. Analysis was by modified intent to treat using a prespecified logistic regression model. Primary, prespecified endpoint was “alive and free from respiratory failure at day 60.”

Results: Across all patients and sites of care, patients treated with aviptadil were significantly more likely to be alive and free from respiratory failure at 60 days, compared to those treated with placebo (P=.02) and demonstrated improvement in survival alone (P<.001). Advantages in survival for aviptadil-treated patients were seen in both the subgroup classified as 2 on the National Institute of Allergy and Infectious Disease (NIAID) ordinal scale (58.6% vs. 0%; LR chi square=10.5, p=.001) and the NIAID=3 subgroup (83.1% vs. 62.8%; LR chi square=5.6, p=.03). Among patients who recovered successfully, those treated with Aviptadil had a median 10-day reduction in length of hospital stay compared to placebo patients (P=.025).

Comment: Treatment with aviptadil demonstrates multi-dimensional efficacy in improving the likelihood of recovery from respiratory failure and survival to 60 days, and markedly reduced hospital stay in critically ill patients with respiratory failure caused by COVID-19.

https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3830051

NRx Pharmaceuticals Announces First Successful Commercial Formulation for ZYESAMI™ (aviptadil), Enabling Volume Manufacture, Shipping, and Stockpiling of COVID-19 Medication Subject to Regulatory Approval

RADNOR, Pa., July 22, 2021 /PRNewswire/ -- NRx Pharmaceuticals (NRx) (Nasdaq: NRXP) announced today it has validated the first commercial formulation of ZYESAMI™ (aviptadil) for intravenous use, allowing for high volume manufacture, with an anticipated one year or greater stability, under appropriate storage conditions. Simultaneously, NRx has achieved a 30-to-50-fold increase in its manufactured lot size of aviptadil, with a concurrent 90% reduction in the cost of its peptide supply. These two developments position NRx to potentially deliver millions of doses of ZYESAMI™ as potential regulatory approvals are obtained in various regions worldwide.

"When we began developing aviptadil for treatment of COVID-19, we discovered that the original RLF-100 formulation and manufacturing method had only a few weeks of stability, leaving hospitals unable to stock the investigational medicine in pharmacies, and leaving aviptadil out of consideration for national strategic stockpiles. Moreover, the high cost of peptide and an inability to manufacture more than 100 grams a month limited the commercial utility of aviptadil," said Prof Jonathan Javitt, MD, MPH, Chairman and CEO of NRx. "We have now turned the corner and can produce both the aviptadil peptide and finished medicine in million dose quantities. We have also developed and validated the first modern chromatography assays required to ensure the purity and stability of the drug product. The new formulation method and high-speed manufacturing process adapts to the fragile nature of vasoactive intestinal peptide."

As the Delta variant and more threatening, newer mutations of the Coronavirus continue to erode the immunity created by first-generation vaccines, NRx is in active discussion with national health ministries and regulators regarding Emergency Use Authorization for ZYESAMI™ (aviptadil). The new formulation allows for the immediate shipping worldwide, upon potential EUA approval.

"Twenty years ago, Dr. Sami Said formulated the first doses of aviptadil by hand in a hospital pharmacy," said Dr. Riccardo Panicucci, a top scientific advisor to NRx. "We began this project a year ago, with 9 days of stability and an ability to manufacture about 100 doses of medicine each day. We learned through significant study and testing that the important biologic activity of this small peptide is accompanied by a fragile molecular structure that is destroyed by standard high-volume pharmaceutical manufacturing processes. Fortunately, we and our manufacturing partners have reached a greater level of commercial manufacturing, just as the pandemic seems poised to enter a new wave."

The successful new formulation and manufacturing scaleup of ZYESAMI™ allows NRx to relaunch its Expanded Access and Right to Try programs as it continues to seek Emergency Use Authorization in the United States. These programs are designed to afford patients at highest risk of death from COVID-19, and who have no other therapeutic options, the ability to access ZYESAMI™ on an investigational basis."

https://www.prnewswire.com/news-releases/nrx-pharmaceuticals-announces-first-successful-commercial-formulation-for-zyesami-aviptadil-enabling-volume-manufacture-shipping-and-stockpiling-of-covid-19-medication-subject-to-regulatory-approval-301339154.html

NRx Pharmaceuticals is the U.S. partner for Relief Therapeutics (Swiss) who developed RLF-100 / Aviptadil / Zyesami, and will lead commercialization in the United States, Canada, and Israel, while Relief will lead commercialization in Europe and the rest of the world. Profits from sales will be allocated to Relief and NeuroRx on a 50/50 basis in the U.S., Canada and Israel, 85/15 (in favor of Relief) in Europe, and 80/20 (in favor of Relief) in all other territories.

https://www.nrxpharma.com/relief-and-neurorx-announce-partnership-for-global-commercialization-of-rlf-100-and-selection-of-commercial-partners/

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