8 unchanged sentences
We need to raise additional capital to operate our business.
−Removed: If we fail to obtain the capital necessary to fund our operations, we will be unable to continue or complete our product development.
−Removed: NRX-100, NRX-101, and ZYESAMI are still in Phase IIb/III of clinical testing, and our initial application to the FDA for Emergency Use Authorization for ZYESAMI was not granted.
+Added: If we fail to obtain the capital necessary to fund our operations, we will be unable to continue as a going concern or complete our product development.
+Added: NRX-101 is in clinical testing and we cannot predict with any certainty if or when we might submit an NDA for regulatory approval.
We have not yet scaled manufacturing of our drug products to levels that are required for sustained sales.
−Removed: The Company has been, and may become involved in, disputes, claims, arbitration and litigation, including our dispute with Relief Therapeutics.
+Added: The Company has been, and may become involved in, disputes, claims, arbitration and litigation.
If we fail to obtain or maintain FDA and other regulatory clearances for our products, or if such clearances are delayed, we will be unable to commercially distribute and market our products in the U.S.
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We are faced with rapid technological change and developments by competitors may render our products or technologies obsolete or non-competitive.
−Removed: We do not anticipate obtaining orphan drug protection for the treatment of COVID-19.
−Removed: Our business activities have been disrupted due to the outbreak of the COVID-19 pandemic.
−Removed: Likewise, we are currently operating in a period of economic uncertainty and capital markets disruption, which has been significantly impacted by geopolitical instability due to the ongoing military conflict between Russia and Ukraine.
+Added: • We are currently operating in a period of economic uncertainty and capital markets disruption, which has been significantly impacted by geopolitical instability due to the ongoing military conflict between Russia and Ukraine.
Our relationships with customers and payors will be subject to applicable anti-kickback, fraud and abuse, transparency, and other healthcare laws and regulations, which could expose us to criminal sanctions, civil penalties, contractual damages, reputational harm, and administrative burdens.
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Conducting clinical trials of our drug candidates or commercial sales of a drug candidate may expose us to expensive product liability claims and we may not be able to maintain product liability insurance on reasonable terms or at all.
−Removed: The use of a controlled substance in our NRX-100 drug candidate subjects us to DEA scrutiny and compliance, which may result in additional expense and clinical delays, and may generate controversy.
−Removed: In addition, the use of controlled substances may limit the availability of the active ingredients needed for NRX-100 and NRX-101.
−Removed: We may need to focus our future efforts in new therapeutic areas where we have little or no experience.
+Added: If the Company pursues development of our NRX-100 drug candidate, the use of a controlled substance subjects us to DEA scrutiny and compliance, which may result in additional expense and clinical delays, and may generate controversy.
+Added: In addition, the use of controlled substances may limit the availability of the active ingredients needed for NRX-100.
Modifications to our products may require new NDA approvals and some of our other product candidates will require Risk Evaluation and Mitigation Strategies.
−Removed: Our formulation of ZYESAMI is not covered by an issued patent and may be subject to future generic competition.
Our business relies on certain licensing rights that can be terminated in certain circumstances.
Our business depends upon securing and protecting critical intellectual property.
−Removed: Our patent position is highly uncertain.
If we are found to be infringing on patents or trade secrets owned by others, we may be forced to cease or alter our product development efforts, obtain a license to continue development or sale of our products, and/or pay damages.
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These manufacturers may fail to satisfy our requirements and applicable regulatory requirements.
−Removed: Upon commercialization of our products, we may be dependent on third parties to market, distribute and sell our products.
−Removed: We may not be successful in contracting with third parties for these services on favorable terms.
Our issuance of additional shares of Common Stock or convertible securities could make it difficult for another company to acquire us, may dilute your ownership of us and could adversely affect our stock price.
Future sales, or the perception of sales, of our Common Stock by us or our existing stockholders could cause the market price for our Common Stock to decline.
−Removed: We qualify as an “emerging growth company” as well as a “smaller reporting company” within the meaning of the Securities Act, which could make our securities less attractive to investors and may make it more difficult to evaluate our performance.
+Added: We qualify as a “smaller reporting company” within the meaning of the Securities Act, which could make our securities less attractive to investors and may make it more difficult to evaluate our performance.
Anti-takeover provisions in our governing documents and under Delaware law could make an acquisition of us more difficult, limit attempts by our stockholders to replace or remove our current management and limit the market price of our Common Stock.
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We are no longer a “controlled company” under the corporate governance rules of Nasdaq.
−Removed: However, during the applicable phase-in periods we may continue to rely on exemptions from certain corporate governance standards.
−Removed: • The obligations associated with being a public company will involve significant expenses, and will require significant resources and management attention, which may divert from our business operations.
+Added: However, we continue to rely on certain exceptions from corporate governance standards.
+Added: If we fail to meet the applicable continued listing requirements of NASDAQ Global Market, NASDAQ may delist our common stock, in which case the liquidity and market price of our common stock could decline.
• We do not intend to pay dividends on our Common Stock for the foreseeable future.
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We need to raise additional capital to operate our business.
−Removed: If we fail to obtain the capital necessary to fund our operations, we will be unable to continue or complete our product development.
+Added: If we fail to obtain the capital necessary to fund our operations, we will be unable to continue or complete our product development and we may not be able to continue as a going concern.
We are a company focused on product development and have not generated any product revenues to date.
Until, and if, we receive approval from the FDA and other regulatory authorities for our product candidates, we cannot sell our drugs and will not have product revenues.
−Removed: We had cash and cash equivalents of approximately $27.6 million as of December 31, 2021, and the Company raised approximately $25 million, before fees and other costs, through a private placement in February 2022.
−Removed: However, we will need to continue to seek capital from time to time to continue the development and potential commercialization of our product candidates and to acquire and develop other product candidates.
−Removed: Accordingly, we believe that we may need to raise substantial additional capital to fund our continuing operations and the development and potential commercialization of our product candidates during calendar year 2022.
+Added: We had cash and cash equivalents of approximately $20.1 million as of December 31, 2022, and the Company raised an additional $2.9 million, before fees and other costs, through an offering in March 2023.
+Added: However, we will need to continue to seek capital from time to time to continue the development and potential commercialization of our product candidates, including any expansion of our clinical programs to facilitate a larger safety database for the use of NRX-101 as a chronic, or chronic-intermittent, treatment as advised by FDA in our recent Type B meeting, and to acquire and develop other product candidates.
+Added: Accordingly, we believe that we will need to raise substantial additional capital to fund our continuing operations and the development and potential commercialization of our product candidates during calendar year 2023.
We may raise capital through future share offerings, the issuance of debt instruments and grant monies.
Our actual capital requirements will depend on many factors.
−Removed: For instance, our business or operations may change in a manner that would consume available funds more rapidly than anticipated and substantial additional funding may be required to maintain operations, fund expansion, develop new or enhanced products, acquire complementary products, business or technologies or otherwise respond to competitive pressures and opportunities, such as a change in the regulatory environment or a change in preferred depression treatment
−Removed: or COVID-19 treatment modalities.
+Added: For instance, our business or operations may change in a manner that would consume available funds more rapidly than anticipated and substantial additional funding may be required to maintain operations, fund expansion, develop new or enhanced products, acquire complementary products, business or technologies or otherwise respond to competitive pressures and opportunities, such as a change in the regulatory environment or a change
+Added: in preferred depression treatment.
If we experience unanticipated cash requirements, we may need to seek additional sources of financing, which may not be available on favorable terms, if at all.
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If we cannot raise adequate funds to satisfy our capital requirements, we will have to delay, scale-back or eliminate our research and development activities, clinical studies or future operations and we may be unable to complete planned nonclinical studies and clinical trials or obtain approval of our product candidates from the FDA and other regulatory authorities.
−Removed: In addition, we could be forced to discontinue product development, reduce or forego sales and marketing efforts and attractive business opportunities, reduce overhead, or discontinue operations.
+Added: In addition, we could be forced to discontinue product development, reduce or forego sales and marketing efforts and attractive business opportunities, reduce overhead, or be unable to continue as a going concern.
We may also be required to obtain funds through arrangements with collaborators, which arrangements may require us to relinquish rights to certain technologies or products that we otherwise would not consider relinquishing, including rights to future product candidates or certain major geographic markets.
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Risks Related to Our Business and Industry
−Removed: NRX-100, NRX-101, and ZYESAMI are still in Phase IIb/III of clinical testing.
+Added: NRX-101 is still in Phase II/III of clinical testing.
NRX-101 is in Phase IIb/III of clinical testing with Breakthrough Therapy designation, a Biomarker Letter and a Special Protocol Agreement issued by the FDA on April 20, 2018.
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FDA approval requires that a drug candidate complete a Phase III study program, which tests the safety and efficacy of the drug candidate on a large sample of patients.
−Removed: We are in the process of closing down t he NRX-101 Phase IIb/III trial (NCT 03396068) in preparation for a new Phase IIb/III clinical study that is expected to start in the second half of 2022 and will trial a commercial formulation of the drug.
+Added: We are conducting a new registrational study of NRX-101 for severe bipolar depression in patients with ASIB after initial stabilization with NRX-100 (ketamine).
+Added: We are using newly-manufactured material that was manufactured using the expected commercial process.
+Added: In addition, we have initiated a Phase II clinical study for bipolar depression with sub-acute suicidal ideation and behavior.
+Added: This population is significantly larger than the Bipolar Depression population with ASIB, and does not require initial stabilization with NRX-100.
+Added: On January 3, 2023, the Company announced that its first clinical trial site had been contracted for a Phase 3 clinical trial of NRX-101 for the treatment of Severe Bipolar Depression in patients with Acute Suicidal Ideation and Behavior, a potentially lethal condition that currently takes the lives of thousands of Americans each year.
Because NRX-101 is a Breakthrough Therapy, we anticipate being able to file a New Drug Application (“NDA”) based upon a single, successful Phase III trial.
−Removed: The FDA has assigned three further nonclinical studies before we can submit an NDA with respect to NRX-101.
−Removed: While we cannot predict with any certainty if or when we might submit an NDA for regulatory approval of NRX-101, we aim to submit an NDA to the FDA for the regulatory approval and commercialization of NRX-101 in the U.S.
−Removed: ZYESAMI is in Phase III of clinical testing with Fast Track Designation issued by the FDA on June 19, 2020.
−Removed: Full FDA approval (as opposed to interim Emergency Use Authorization) requires that a drug candidate complete a Phase III study program, which tests the safety and efficacy of the drug candidate on a large sample of patients.
−Removed: The Phase III study program is being conducted by the NIH as part of the ACTIV-3b program and we are designated as an industry partner by the NIH.
−Removed: We are responsible for the costs of supplying investigational ZYESAMI to this program and for ongoing regulatory support of our investigational product.
−Removed: The ACTIV-3b:
−Removed: Therapeutics for Severely Ill Inpatients With COVID-19 (TESICO) trial (NCT 04833761) remains open and is anticipated to conclude in the second half of 2022.
−Removed: If this trial is successful, and there are no guarantees that it will be, the trial would confirm the findings of our completed ZYESAMI trial and we would anticipate being able to file an NDA towards the end of 2022, subject to the receipt of required data from the NIH.
−Removed: Failure to obtain FDA approval of ZYESAMI, or a delay in our submission of an NDA for approval of ZYESAMI, could have a material adverse effect on our business and results of operations.
−Removed: Our initial application to the FDA for Emergency Use Authorization of ZYESAMI was not granted.
−Removed: In the setting of a public health emergency, the FDA has authority to grant Emergency Use Authorization (“EUA”) for drugs that are safe and “may be effective” to meet unmet medical needs ahead of their FDA approval.
−Removed: We filed for EUA for ZYESAMI on May 31, 2021 with the FDA.
−Removed: In November 2021, the FDA notified the Company that it was unable to issue the EUA at that time due to insufficient data regarding the known and potential benefits of ZYESAMI and the known and potential risks of ZYESAMI in patients suffering from Critical COVID-19 with respiratory failure.
−Removed: In its letter, the FDA noted that so far, it has reviewed safety in only 131 randomized patients treated with ZYESAMI.
−Removed: Based on feedback received from the FDA to our Breakthrough Therapy designation request, the Company has narrowed its EUA request to the treatment of patients with COVID-19 respiratory failure who are at risk of death despite treatment with remdesivir and other approved therapies, and has submitted a new request for EUA to the FDA for permission to distribute ZYESAMI.
−Removed: As of the date of this annual report, that request is still pending.
−Removed: Should the EUA eventually be granted in the U.S., this would provide us with the ability to distribute ZYESAMI for the treatment of the sickest patients with COVID-19 in advance of an NDA.
−Removed: There can be no assurance, however, that we will be granted an EUA by the FDA.
−Removed: If the EUA is not granted we may never be able to commercialize ZYESAMI in the U.S.
−Removed: or recoup costs expended in its trials.
−Removed: FDA has not explained how the Congressionally-mandated standard of “may be effective” will be applied to ZYESAMI in FDA’s consideration of any future application for Emergency Use Authorization.
−Removed: EUA is a form of temporary marketing authorization that the FDA may grant to an investigational drug at times when the Secretary of Health and Human Services has declared a Public Health Emergency to exist.
−Removed: This declaration was made by the Secretary of Health and Human Services in March 2020 in relation to the COVID-19 pandemic.
−Removed: In order to grant EUA, the FDA must determine that an investigational drug “may be effective” in treating the disease that is the subject of the Public Health Emergency.
−Removed: The FDA has not advised us how it will determine whether efficacy has been demonstrated in the
−Removed: context of any future EUA request relating to COVID-19 with respiratory failure.
−Removed: An FDA determination that ZYESAMI does not meet the “may be effective” standard could have a material adverse effect on our business and results of operations.
+Added: While we cannot predict with any certainty if or when we might submit an NDA for regulatory approval of NRX-101, we aim to submit an NDA to the FDA on a rolling basis for the regulatory approval and commercialization of NRX-101 in the U.S.
Our product candidates are newly-formulated and we have not yet scaled manufacturing to levels that will be required for sustained sales.
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, five years) has been achieved for our solid dose formulation of NRX-101.
−Removed: This formulation is deemed ready for transfer to a commercial scale cGMP manufacturing facility.
−Removed: Prior to our involvement, aviptadil was never formulated in a manner that provided adequate shelf stability for commercial release as an intravenous medication.
−Removed: We partnered with Nephron Pharmaceuticals Corporation (“Nephron Pharmaceuticals”) to develop a long-term stable commercial presentation of aviptadil.
−Removed: We identified several root causes of prior instability and identified a path to a long-term shelf stable product.
−Removed: In July 2021, we announced the development of a formulation, manufacturing, and container closure system that has thus far demonstrated 150-180 day refrigerated stability and gives indications of yielding substantially longer stability while frozen.
−Removed: However, our manufacturing method has been tested so far at the 50 liter per batch scale, sufficient to manufacture approximately 10,000 patient doses per manufacturing batch.
−Removed: Although the Company estimates that this is sufficient scale to produce approximately 1 million doses of ZYESAMI per year at our current manufacturing capability, we have yet to scale manufacture to the targeted 500 liter per batch scale that will be capable of manufacturing 100,000 patient doses per manufacturing batch.
−Removed: In order to achieve long-term ( i.e., multiyear) stability we may be forced to supply ZYESAMI in frozen presentation which would increase our supply chain costs and make our product less attractive to end-users than products that can be stored at room temperature or under non-freeze refrigeration.
−Removed: The outcome of any current or future disputes, claims, arbitration and litigation, including our dispute with Relief Therapeutics could have a material adverse effect on our business, financial condition and results of operations.
−Removed: We are currently involved in a dispute with Relief Therapeutics Holding AG (“Relief Therapeutics”).
−Removed: We entered into a Collaboration Agreement with Relief Therapeutics (the “Collaboration Agreement”) on September 18, 2020.
−Removed: The Collaboration Agreement is limited to collaboration around “Product,” which is defined as any formulation of aviptadil for which Relief Therapeutics has paid the costs of research and development.
−Removed: Under that agreement, Relief Therapeutics was required to fund the development costs related to aviptadil for treatment of COVID-19 in exchange for a predetermined division of profits and we had the right to continue its development program with other investor funds should Relief Therapeutics not provide funding.
−Removed: Shortly following the entry into the Collaboration Agreement , however, a number of disputes arose between Relief Therapeutics and the Company, including with respect to the scope of clinical trials of aviptadil for treatment of COVID-19 respiratory failure and the stability of the original formulation for aviptadil.
−Removed: In February 2021, Relief Therapeutics ceased funding further development of aviptadil for the treatment of COVID-19 and advised us that it would not fund clinical trials for its inhaled use.
−Removed: Furthermore, Relief Therapeutics did not fund the cost of reformulation necessary to develop a shelf stable product (reformulated as ZYESAMI).
−Removed: Accordingly, we exercised our option under the Collaboration Agreement to bring investment from other sources to continue research and development.
−Removed: On October 6, 2021, Relief Therapeutics filed a complaint in New York State Court (“NYS Court”), claiming that we failed to honor our obligations under the Collaboration Agreement (the “Complaint”).
−Removed: The Complaint seeks several remedies including damages for alleged breaches of the terms of the Collaboration Agreement.
−Removed: We believe that the claims are baseless and without merit.
−Removed: In addition to asking the NYS Court to enter summary judgment in favor of NRx with regard to Relief Therapeutics’ demand to receive profit without having funded the underlying product, NRx has filed a complaint seeking damages of at least $185 million.
−Removed: However, the parties to the lawsuits agreed to engage in an effort to amicably resolve the litigation, held a mediation meeting on February 22, 2022, and plan to hold an additional mediation meeting in the coming months.
−Removed: If the mediation does not resolve the dispute, the Company intends to defend itself vigorously and to prosecute its claims against Relief Therapeutics .
−Removed: There can be no assurance, however, that we will be able to successfully resolve the dispute
−Removed: through mediation or that, in the event the dispute continues in litigation, we will be successful in our claims against Relief Therapeutics or our opposition to Relief Therapeutics’ claims.
+Added: Although the Company completed a Type C meeting in which FDA agreed to the Company's Chemical Manufacturing Control and stability program for drug manufacture, and production of NRx-101 has been transferred to a commercial scale cGMP manufacturing facility in South Carolina, we have yet to attempt large scale manufacturing.
+Added: The outcome of any current or future disputes, claims, arbitration and litigation could have a material adverse effect on our business, financial condition and results of operations.
+Added: We are currently involved in a dispute with GEM Yield Bahamas Limited and GEM Global Yield LLC SCS (collectively, “GEM”).
+Added: On August 12, 2022, the Company received a demand for arbitration (the “Demand”) from GEM.
+Added: The Demand claims that the Company’s subsidiary, NeuroRx, Inc.
+Added: (“NeuroRx”), failed to satisfy its obligation to pay GEM a commitment fee in the amount of HK$ 15,000,000 (approximately US$[1,914,087] at current exchange rates) pursuant to a Share Subscription Facility Agreement, executed on October 18, 2019, by and among NeuroRx and GEM.
+Added: NeuroRx expects to vigorously defend its position that payment of the commitment fee is neither due nor owing under the terms of the Agreement.
In the event of an adverse ruling, there can be no assurance that we would not be required to pay damages in an amount that may have a material adverse effect on our business, financial condition or results of operations.
−Removed: If we fail to obtain or maintain FDA and other regulatory clearances for our products, or if such clearances are delayed, we will be unable to commercially distribute and market our products in the U.S.
−Removed: and in some international territories.
+Added: If we fail to obtain or maintain FDA and other regulatory clearances for our products, or if such clearances are delayed, we will be unable to commercially distribute and market our products.
Our products are subject to rigorous regulation by national regulators around in the world, and by the FDA in the U.S .
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Any NDA application filed by us will have to be supported by extensive data, including, but not limited to, technical, nonclinical, clinical trial, manufacturing and labelling data, to demonstrate to the FDA’s satisfaction the safety and efficacy of the product for its intended use.
−Removed: In general, an NDA for a non-Breakthrough Therapy requires two clinical trials that meet pre-specified statistical endpoints.
−Removed: We have already completed a 196-person Phase IIb/III clinical trial of intravenous ZYESAMI for the treatment of respiratory failure in patients with critical COVID-19 (NCT04311697) and a 250+ person Expanded Access Protocol (NCT04311697).
−Removed: The trial approached, but failed to reach statistical significance on its primary endpoint of time recovery from respiratory failure, reaching a P value of .085.
−Removed: However, the trial demonstrated a statistically-significant two- fold improvement in odds of survival (P=.03) across all patients and sites of care.
−Removed: The trials additionally demonstrated a statistically-significant difference in the primary endpoint of being alive and free of respiratory failure at 60 days among patients treated in tertiary care hospitals but not among patients treated at regional hospitals.
−Removed: As described above, the NIH has launched a Phase III trial, funded by the National Institute of Allergy and Infectious Diseases (“ NIAID ”), which compares ZYESAMI to placebo and Veklury (remdesivir), a COVID-19 treatment offered by Gilead Sciences alone and in combination with ZYESAMI.
−Removed: This trial is called ACTIV-3b:
−Removed: Therapeutics for Severely Ill Inpatients With COVID-19 (TESICO) (NCT 04843761), and it began enrolling patients in April 2021.
−Removed: Should it achieve its primary endpoint of increased likelihood of recovery from respiratory failure at 90 days compared to placebo, this trial could qualify as a second Phase III trial in support of an NDA for ZYESAMI.
−Removed: We cannot predict with any certainty whether this trial will achieve its primary endpoint or if or when we might submit an NDA for regulatory approval, although we aim to submit an NDA to the FDA for accelerated approval of ZYESAMI for the treatment of COVID-19 by the end of 2022.
−Removed: Safety and efficacy determinations are within FDA’s purview and clinical trial results do not guarantee regulatory approval.
−Removed: Failure to obtain FDA approval of ZYESAMI, or a delay in our submission of an NDA for approval of ZYESAMI, could have a material adverse effect on our business and results of operations.
Obtaining clearances or approvals from the FDA and from the regulatory agencies in other countries could result in unexpected and significant costs for us and consume management’s time and other resources.
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We may have conflicts with our partners that could delay or prevent the development or commercialization of our product candidates.
−Removed: Aside from the Complaint and our other disagreements with Relief Therapeutics, we are not aware of any material commercial conflicts that could delay or prevent development or commercialization.
+Added: We are not aware of any material commercial conflicts that could delay or prevent development or commercialization.
However, commercial conflicts such as the interpretation of contractual obligations, payments for services, development obligations or the ownership of intellectual property could arise in any joint development activity.
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Our chief competitors in the psychiatry area include companies such as Johnson & Johnson, Pfizer, Eli Lilly, Sage Therapeutics, Axsome, and Relmada, among others.
−Removed: I n the COVID-19 space it is likely that multiple products with approval and/or authorization to be used in this population will be used concurrently, e.g.
−Removed: steroids, remdesivir, tocilizumab, etc.
−Removed: We are not aware of any other investigational COVID-19 therapeutics that have a similar mechanism of action as ZYESAMI.
−Removed: Yet, the emergence of new and increased use of new treatment agents in the earlier stages of the
−Removed: COVID-19 could limit the market potential.
−Removed: Companies with emerging earlier therapeutics include Pfizer, Astra-Zeneca, Lilly, Regeneron, etc.
−Removed: Furthermore, many new vaccines are in development.
We are faced with intense competition and rapid technological change, which may make it more difficult for us to achieve significant market penetration.
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and the level of education and awareness among physicians and hospitals concerning our products.
−Removed: Failure of any of our products to significantly penetrate current or new markets would negatively impact our business, financial condition and results of operations.
+Added: The failure of any of our products to significantly penetrate current or new markets would negatively impact our business, financial condition and results of operations.
To be commercially successful, physicians must be persuaded that using our products are effective alternatives to existing therapies and treatments.
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Even if our agreements with any future corporate collaborators entitle us to indemnification against losses, such indemnification may not be available or adequate if any claim arises.
−Removed: We do not anticipate obtaining orphan drug protection for the treatment of COVID-19.
−Removed: The Orphan Drug Act provides incentives for the development of drugs intended to treat rare diseases or conditions, which generally are diseases or conditions affecting less than 200,000 individuals annually in the U.S.
−Removed: , or affecting more than 200,000 in the U.S.
−Removed: and for which there is no reasonable expectation that the cost of developing and making the drug available in the U.S.
−Removed: will be recovered from U.S.
−Removed: Orphan drug designation entitles a party to financial incentives such as opportunities for grant funding towards clinical study costs, tax advantages, and user-fee waivers.
−Removed: Further, if a product that has orphan drug designation subsequently receives FDA approval for the indication for which it has such designation, the product is entitled to orphan exclusivity, ( i.e.
−Removed: , for seven years), the FDA may not approve any other applications to market the same drug for the same indication, except in very limited circumstances, including if a competitive product is shown to be clinically superior to the product that was granted orphan exclusivity.
−Removed: COVID-19 is not considered a rare disease and the FDA has advised us that any potential benefits afforded to aviptadil based on an orphan drug designation would not apply to its use for the treatment of COVID-19.
We may not be able to obtain Hatch-Waxman Act marketing exclusivity or equivalent regulatory data exclusivity protection in other jurisdictions for our products.
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Future collaborations with foreign partners may not be effective or profitable for us.
−Removed: Our business activities have been disrupted due to the outbreak of the COVID-19 pandemic.
−Removed: Despite the fact that some of our products are designed to combat COVID-19, we face the same risks and uncertainties that challenge all pharmaceutical companies related to the global outbreak of a new strain of COVID-19.
−Removed: In recent months, the continued spread of COVID-19 has led to disruption and volatility in the global economy and capital markets, which increases the cost of capital and adversely impacts access to capital.
−Removed: Government-enforced travel bans, business closures, and work-from-home or shelter-in-place orders around the world have significantly impacted our ability to conduct clinical trials, obtain supplies of needed materials and, in general, further the development of our business.
−Removed: It has, and may continue to, disrupt our third-party contract manufacturers and supply chain.
−Removed: We have also incurred increased overhead costs associated with the COVID-19 pandemic, including costs arising from protocols intended to reduce the risk of transmission among our employees and business partners.
−Removed: Furthermore, if significant portions of our workforce are unable to work effectively, including because of illness, quarantines, safety considerations, government actions, facility closures, remote working or other restrictions in connection with the COVID-19 pandemic, our operations will likely be adversely impacted.
−Removed: Further, the COVID-19 pandemic, and the volatile global economic conditions stemming from the pandemic, could precipitate or amplify the other risks that we identify in this “ Risk Factors ” section.
+Added: Our business activities could face further disruption due to the COVID-19 pandemic.
We are continuing to monitor the latest developments regarding the COVID-19 pandemic on our business, operations and financial condition and results, and have made certain assumptions regarding the pandemic for purposes of our operational planning and financial projections, including assumptions regarding the duration and severity of the pandemic and the global macroeconomic impact of the pandemic.
−Removed: Despite careful tracking and planning, however, we are unable to accurately predict the extent of the impact of the pandemic on our business, operations and financial condition and results due to the uncertainty
−Removed: of future developments.
−Removed: If the COVID-19 pandemic continues for a prolonged duration, the research and development of our products will be delayed and we may be unable to perform fully on our contracts, which will likely result in increases in costs and reduction in revenue.
+Added: Despite careful tracking and planning, however, we are unable to accurately predict the extent of the impact of the pandemic on our business, operations and financial condition and results due to the uncertainty of future developments.
+Added: If there is a resurgence of the COVID-19 pandemic, the research and development of our products will be delayed and we may be unable to perform fully on our contracts, which will likely result in increases in costs and reduction in revenue.
These cost increases may not be fully recoverable or adequately covered by insurance.
−Removed: The long-term effects of the COVID-19 pandemic to the global economy and to us are difficult to assess or predict and may include a decline in the market prices of our products, risks to employee health and safety, risks for the deployment of our products and services and reduced sales in geographic locations impacted.
−Removed: Any prolonged restrictive measures put in place in order to control the COVID-19 pandemic or other adverse public health developments in any of our targeted markets may have a material and adverse effect on our business operations and results of operations.
+Added: The long-term effects of the COVID-19 pandemic to the global economy and to us continue to be difficult to assess or predict and may include a decline in the market prices of our products, risks to employee health and safety, risks for the deployment of our products and services and reduced sales in geographic locations impacted.
+Added: Any prolonged restrictive measures put in place to control a resurgence of the COVID-19 pandemic or other adverse public health developments in any of our targeted markets may have a material and adverse effect on our business operations and results of operations.
For additional information on how the COVID-19 pandemic has already impacted our business, operations and financial condition and results, see our historical consolidated financial statements, presented elsewhere in this annual report.
8 unchanged sentences
social, political, regulatory and economic conditions or in laws and policies governing foreign trade, manufacturing, development and investment could also adversely affect our business.
−Removed: For example, the ongoing negotiations about transitioning the United Kingdom from the European Union following its formal exit on January 31, 2020 has increased the regulatory burden associated with the separation of the U.K.
−Removed: Medicines Authority from the European Medicines Authority and may result in the imposition of tariffs that could have an adverse impact on our results of operation.
−Removed: Additionally, there also is a risk that other countries may decide to leave the European Union.
−Removed: This uncertainty surrounding this transition not only potentially affects our business opportunities in the United Kingdom and the European Union, but also may have an effect on global economic conditions and the stability of global financial markets, which in turn could have a material adverse effect on our business, financial condition and results of operations.
−Removed: In extreme cases, we could experience interruptions in production due to the processing of customs formalities or reduced customer spending in the wake of weaker economic performance.
−Removed: If global economic conditions remain volatile for a prolonged period or if European economies experience further disruptions, our results of operations could be adversely affected.
−Removed: We are currently operating in a period of economic uncertainty and capital markets disruption, which has been significantly impacted by geopolitical instability due to the ongoing military conflict between Russia and Ukraine.
−Removed: Our business, financial condition, and results of operations may be materially adversely affected by the negative impact on the global economy and capital markets resulting from the conflict in Ukraine or any other geopolitical tensions.
−Removed: and global markets are experiencing volatility and disruption following the escalation of geopolitical tensions and the start of the military conflict between Russia and Ukraine.
−Removed: On February 24, 2022, a full-scale military invasion of Ukraine by Russian troops began.
−Removed: Although the length and impact of the ongoing military conflict is highly unpredictable, the conflict in Ukraine has led to market disruptions, including significant volatility in commodity prices, credit and capital markets, as well as supply chain disruptions.
−Removed: Additionally, various of Russia’s actions have led to sanctions and other penalties being levied by the U.S., the European Union, and other countries, as well as other public and private actors and companies, against Russia and certain other geographic areas, including agreement to remove certain Russian financial institutions from the Society for Worldwide Interbank Financial Telecommunication payment system and restrictions on imports of Russian oil, liquified natural gas and coal.
−Removed: Additional potential sanctions and penalties have also been proposed and/or threatened.
−Removed: Russian military actions and the resulting sanctions could further adversely affect the global economy and financial markets and lead to instability and lack of liquidity in capital markets, potentially making it more difficult for us to obtain additional funds.
−Removed: Any of the above-mentioned factors could affect our business, prospects, financial condition, and operating results.
−Removed: The extent and duration of the military action, sanctions, and resulting market disruptions are impossible to predict, but could be substantial.
+Added: Our business, financial condition, and results of operations may be materially adversely affected by the negative impact on the global economy and capital markets resulting from new international conflicts or any other geopolitical tensions.
+Added: and global markets generally experience volatility and disruption as a result of geopolitical tensions and military conflicts, including significant volatility in commodity prices, credit and capital markets, as well as supply chain disruptions.
+Added: Additionally, international sanctions and other penalties can disrupt payment systems and imports/exports and lead to instability and lack of liquidity in capital markets, potentially making it more difficult for us to obtain additional funds.
Any such disruptions may also magnify the impact of other risks described in this annual report.
We may not be successful in hiring and retaining key employees and contractors.
−Removed: Our future operations and successes depend in large part upon the continued service of key members of our senior management team whom we are highly dependent upon to manage our business, including our interim Chief Executive Officer.
+Added: Our future operations and successes depend in large part upon the continued service of key members of our senior management team whom we are highly dependent upon to manage our business, including our Chief Executive Officer.
If he terminates his relationship with us, such a departure could have a material adverse effect on our business.
2 unchanged sentences
We compete for qualified individuals with numerous biopharmaceutical companies, universities and other research institutions.
−Removed: Competition for such individuals, particularly in the U.S.
−Removed: , is intense, and we may not be able to hire sufficient personnel to support our efforts.
+Added: Competition for such individuals, particularly in the U.S., is intense, and we may not be able to hire sufficient personnel to support our efforts.
There can be no assurance that these professionals will be available in the market, or that we will be able to retain existing professionals or to meet or to continue to meet their compensation requirements.
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• comply with FDA regulations or similar regulations of comparable foreign regulatory authorities;
−Removed: provide accurate information to the FDA or comparable foreign regulatory authorities;
+Added: provide accurate
+Added: information to the FDA or comparable foreign regulatory authorities;
• comply with federal and state healthcare fraud and abuse laws and regulations and similar laws and regulations established and enforced by comparable foreign regulatory authorities;
4 unchanged sentences
Employee misconduct could also involve the improper use of information obtained in the course of clinical trials, which could result in regulatory sanctions and serious harm to our reputation.
−Removed: We have adopted a Business Code of Conduct and Anti-Corruption Policy, but it is not always possible to identify and deter employee misconduct, and the precautions we take to detect and prevent this activity may not be effective in controlling unknown or
−Removed: unmanaged risks or losses or in protecting us from governmental investigations or other actions or lawsuits stemming from a failure to be in compliance with such laws or regulations.
+Added: We have adopted a Business Code of Conduct and Anti-Corruption Policy, but it is not always possible to identify and deter employee misconduct, and the precautions we take to detect and prevent this activity may not be effective in controlling unknown or unmanaged risks or losses or in protecting us from governmental investigations or other actions or lawsuits stemming from a failure to be in compliance with such laws or regulations.
If any such actions are instituted against us, and we are not successful in defending ourselves or asserting our rights, those actions could have a significant impact on our business and results of operations, including the imposition of significant fines or other sanctions.
11 unchanged sentences
• state and foreign anti-kickback and false claims laws, which may apply to sales or marketing arrangements and claims involving healthcare items or services reimbursed by non-governmental payors, including private insurers;
−Removed: • the federal Health Insurance Portability and Accountability Act of 1996 (“HIPAA”), as amended by the Health Information Technology for Economic and Clinical Health Act of 2009 (“HITECH”), which imposes criminal and civil liability for executing a scheme to defraud any healthcare benefit program or making false statements relating to healthcare matters;
+Added: • the federal Health Insurance Portability and Accountability Act of 1996 (“HIPAA”), as amended by the Health
+Added: Information Technology for Economic and Clinical Health Act of 2009 (“HITECH”), which imposes criminal and civil liability for executing a scheme to defraud any healthcare benefit program or making false statements relating to healthcare matters;
• HIPAA and its implementing regulations, which also imposes obligations on certain covered entity healthcare providers, health plans, and healthcare clearinghouses as well as their business associates that perform certain services involving the use or disclosure of individually identifiable health information, including mandatory contractual terms, with respect to safeguarding the privacy, security and transmission of individually identifiable health information;
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Alternative technologies and products are being developed to treat depression and some may target suicidal bipolar depression and post-traumatic stress disorder (“PTSD”).
−Removed: Numerous sponsors are attempting to develop drugs to treat or prevent progression to Critical COVID-19.
−Removed: Many of these organizations competing with us have substantially greater capital resources, larger research and development staffs and facilities, greater experience in drug development and in obtaining regulatory approvals and greater manufacturing and marketing capabilities than we do.
+Added: Many of the organizations competing with us have substantially greater capital resources, larger research and development staffs and facilities, greater experience in drug development and in obtaining regulatory approvals and greater manufacturing and marketing capabilities than we do.
Our competitors may market less expensive or more effective drugs that would compete with our drug candidates or reach market with competing drugs before we are able to reach market with our drug candidates.
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The process of designing and implementing effective internal controls is a continuous effort that will require us to anticipate and react to changes in our business and the economic and regulatory environments and to expend significant resources to maintain a system of internal controls that is adequate to satisfy our reporting obligations as a public company.
−Removed: For the year ended December 31, 2021, our management has identified a material weakness in our internal controls.
−Removed: ( See Section 9A(a) Evaluation of Disclosure Controls and Procedures .)
−Removed: Going forward, if we are unable to establish and maintain appropriate internal financial reporting controls and procedures, in accordance with Section 404 of the Sarbanes-Oxley Act, it could impact our operating results, result in material misstatements in our consolidated financial statements and cause us to fail to meet our reporting obligations on a timely basis.
+Added: If we are unable to establish and maintain appropriate internal financial reporting controls and procedures, in accordance with Section 404 of the Sarbanes-Oxley Act, it could impact our operating results, result in material misstatements in our consolidated financial statements and cause us to fail to meet our reporting obligations on a timely basis.
Testing and maintaining internal controls may divert management’s attention from other matters that are important to our business.
Our independent registered public accounting firm may be required to attest to the effectiveness of our internal control over financial reporting on an annual basis in the future.
−Removed: However, while we remain an emerging growth company or
−Removed: smaller reporting company, we will not be required to include an attestation report on internal control over financial reporting issued by our independent registered public accounting firm.
Matters impacting our internal controls may cause us to be unable to report our financial information on a timely basis and thereby subject us to adverse regulatory consequences, including sanctions by the SEC or violations of applicable stock exchange listing rules, which may result in a breach of the covenants under existing or future financing arrangements.
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If we fail to obtain the necessary regulatory approvals, or if such approvals are limited, we will not be allowed to commercialize our drug candidates, and we will not generate product revenues.
−Removed: In jurisdictions outside the U.S., we and any local collaborators we work with must receive marketing authorizations from the appropriate regulatory authorities before commercializing our drugs.
−Removed: Regulatory approval processes outside the U.S.
−Removed: generally include all of the aforementioned requirements and risks associated with FDA approval, and may impose different or additional steps not required by the FDA.
Satisfaction of all regulatory requirements for commercialization of a drug candidate typically takes many years, is dependent upon the type, complexity and novelty of the product candidate, and requires the expenditure of substantial resources for research and development.
−Removed: Although the FDA is frequently named, the risks described relate to all regulatory interactions we may have around the world.
Our research and clinical approaches may not lead to drugs that regulators consider safe for humans and effective for indicated uses we are studying.
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Failure can occur at any stage of the clinical trials, and we could encounter problems that cause abandonment or repetition of clinical trials.
−Removed: The success in clinical trials depends on reaching statistically significant changes in patients’
−Removed: symptoms based on clinician-rated scales.
+Added: The success in clinical trials depends on reaching statistically significant changes in patients’ symptoms based on clinician-rated scales.
Due in part to a lack of consensus on standardized processes for assessing clinical outcomes, these scores may or may not be reliable, useful or acceptable to regulatory agencies.
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There is no guarantee that regulatory authorities will grant NDA approval of our current or future product candidates and failure to obtain necessary clearances or approvals for our current and future product candidates would adversely affect our ability to grow our business.
−Removed: We have completed a Phase IIb/III clinical trial for ZYESAMI, and in the future expect to submit an NDA to the FDA for approval of ZYESAMI for the treatment of COVID-19 based on the recently completed clinical trial and additional clinical trials currently underway, including the NIH ACTIV3b/TESICO trial (NCT 04843761).
We initiated a Phase IIb/III clinical research program of NRX-101 during the second half of 2017 under an FDA Investigational New Drug (“IND”) application that was granted Fast Track designation by the FDA in August 2017 and was granted the Breakthrough Therapy designation by the FDA in November 2018.
1 unchanged sentence
We successfully completed a Phase II clinical trial of NRX-101 in patients with severe bipolar depression and acute suicidal ideation following stabilization with a single dose of ketamine and saw a statistically significant reduction in depression (P=0.04) and suicidal ideation (P=0.02) compared to lurasidone alone over 42 days of treatment.
−Removed: If this statistically-significant advantage is replicated in the Phase III clinical trial, under the terms agreed to with the FDA in our Special Protocol Agreement, we aim to submit a NDA to the FDA for the regulatory approval and commercialization of NRX-101 in the U.S.
−Removed: We expect to explore regulatory submissions with regulatory authorities of other regions or countries by the end of 2023.
−Removed: We cannot assure investors that the FDA or any other regulator will approve or clear ZYESAMI, NRX-101, or other product candidates for the indications that are necessary or desirable for successful commercialization.
+Added: If this statistically-significant advantage is replicated in the current Phase III clinical trial, under the terms agreed to with the FDA in our Special Protocol Agreement, we aim to submit a NDA to the FDA [on a rolling basis] for the regulatory approval and commercialization of NRX-101 in the U.S.
+Added: We cannot assure investors that the FDA or any other regulator will approve or clear NRX-101 or other product candidates for the indications that are necessary or desirable for successful commercialization.
Indeed, the FDA may refuse our requests for NDA market approval of new products, new intended uses or indications to existing or future products.
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In addition, changes in regulatory requirements and guidance may occur and we may need to amend clinical trial protocols to reflect these changes, which could impact the cost, timing or successful completion of a clinical trial.
−Removed: If we experience delays in the commencement or completion of our clinical trials, the commercial prospects for our product candidates will be harmed, and our ability to generate product revenues will be delayed.
+Added: If we experience delays in the commencement or completion of our clinical trials, the commercial prospects for our product
+Added: candidates will be harmed, and our ability to generate product revenues will be delayed.
Many of the factors that cause, or lead to, a delay in the commencement or completion of clinical trials may also lead to the denial of regulatory approval of a product candidate.
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In addition, depending on the magnitude and nature of the changes made, the regulatory authority could take the position that the data generated by the clinical trial cannot be pooled because the same protocol was not used throughout the trial.
−Removed: This might require the
−Removed: enrollment of additional subjects, which could result in the extension of the clinical trial and the FDA delaying clearance or approval of a product.
+Added: This might require the enrollment of additional subjects, which could result in the extension of the clinical trial and the FDA delaying clearance or approval of a product.
There can be no assurance that the data generated using modified protocols will be acceptable to regulators.
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Serious injury or death resulting from a failure of one of our drug candidates during current or future clinical trials could result in the regulators delaying our clinical trials or denying or delaying clearance or approval of a product.
−Removed: Even though an adverse event may not be the result of the failure of our drug candidate, the regulators or an IRB could delay or halt a clinical trial for an indefinite period of time while an adverse event is reviewed, and likely would do so in the event of multiple such events.
+Added: Even though an adverse event may not be the result of the failure of our drug candidate, the regulators or an IRB could delay or
+Added: halt a clinical trial for an indefinite period of time while an adverse event is reviewed, and likely would do so in the event of multiple such events.
Any delay or termination of our current or future clinical trials as a result of the risks summarized above, including delays in obtaining or maintaining required approvals from IRBs, delays in patient enrollment, the failure of patients to continue to participate in a clinical trial, and delays or termination of clinical trials as a result of protocol modifications or adverse events during the trials, may cause an increase in costs and delays in the filing of any product submissions with the FDA, delay the approval and commercialization of our products or result in the failure of the clinical trial, which could adversely affect our business, operating results and prospects.
15 unchanged sentences
In addition, we may be required to conduct costly post-market testing and surveillance to monitor the safety or effectiveness of our products, and we must comply with adverse event and pharmacovigilance reporting requirements, including the reporting of adverse events which occur in connection with, and whether or not directly related to, our products.
−Removed: Later discovery of previously unknown problems with our products, including unanticipated adverse events or adverse events of unanticipated severity or frequency, manufacturing problems, or failure to comply with regulatory requirements, may result in changes to labeling, restrictions on such products or manufacturing processes, withdrawal of the products from the market, voluntary or mandatory recalls, a requirement to recall, replace or refund the cost of any product we manufacture or distribute, fines, suspension of regulatory approvals, product seizures, injunctions or the imposition of civil or criminal penalties which would adversely affect our business, operating results and prospects.
+Added: Later discovery of previously unknown problems with our products, including unanticipated adverse events or adverse
+Added: events of unanticipated severity or frequency, manufacturing problems, or failure to comply with regulatory requirements, may result in changes to labeling, restrictions on such products or manufacturing processes, withdrawal of the products from the market, voluntary or mandatory recalls, a requirement to recall, replace or refund the cost of any product we manufacture or distribute, fines, suspension of regulatory approvals, product seizures, injunctions or the imposition of civil or criminal penalties which would adversely affect our business, operating results and prospects.
Future government regulation may affect the commercialization of our product candidate.
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The use of a controlled substance in our NRX-100 drug candidate subjects us to DEA scrutiny and compliance, which may result in additional expense and clinical delays.
−Removed: Drug Enforcement Administration (“DEA”) regulates chemical compounds as Schedule I, II, III, IV or V substances, with Schedule I substances considered to present the highest risk of substance abuse and Schedule V substances the
+Added: Drug Enforcement Administration (“DEA”) regulates chemical compounds as Schedule I, II, III, IV or V substances, with Schedule I substances considered to present the highest risk of substance abuse and Schedule V substances the lowest risk.
One of the ingredients in NRX-100 is ketamine, a Schedule III controlled substance with high abuse potential.
Consequently, the manufacture, research, shipment, storage, sale and use of this drug candidate is subject to a high degree of oversight and regulation.
−Removed: None of our other drugs currently under development, including NRX-101 and ZYESAMI, include a scheduled chemical compound.
+Added: None of our other drugs currently under development, including NRX-101, include a scheduled chemical compound.
DEA oversight and regulation can have the following impact on our efforts to develop new drug candidates:
4 unchanged sentences
• the DEA regulates the handling of controlled substances through a closed chain of distribution.
−Removed: This control extends to the equipment and raw materials used in their manufacture and packaging in order to prevent loss and diversion into illicit channels of commerce, which limits our ability to increase the availability of any controlled substances needed for clinical trials or commercial manufacturing.
+Added: This control extends to the equipment and raw materials used in their manufacture and packaging in order to prevent loss and
+Added: diversion into illicit channels of commerce, which limits our ability to increase the availability of any controlled substances needed for clinical trials or commercial manufacturing.
Annual registration is required for any facility that manufactures, distributes, dispenses, imports or exports any controlled substance.
12 unchanged sentences
Individual states also independently regulate controlled substances.
−Removed: There are limitations on the availability of controlled substances used in NRX-100 that may limit the availability of the active ingredients in certain of NRX-100 and NRX-101.
+Added: There are limitations on the availability of controlled substances used in NRX-100 that may limit the availability of the active ingredients for this drug product.
The DEA limits the availability and production of all scheduled substances, including ketamine, through a quota system.
The DEA requires substantial evidence and documentation of expected legitimate medical and scientific needs before assigning quotas to manufacturers.
−Removed: In future years, we may need greater amounts of controlled substances to sustain our Phase IIb/III development program for NRX-100 and NRX-101, and we will need significantly greater amounts to implement our commercialization plans if the FDA approves our proposed formulations.
+Added: In future years, we may need greater amounts of controlled substances to sustain our Phase IIb/III development program for NRX-101 after stabilization with NRX-100, and we will need significantly greater amounts to implement our commercialization plans if the FDA approves our proposed formulations.
Any delay or refusal by the DEA in establishing the procurement quota or a reduction in our quota for scheduled controlled substances or a failure to increase it over time as we anticipate could delay or stop the clinical development or commercial sale of some of our products or product candidates.
2 unchanged sentences
Schedule III drugs have lower abuse potential than Schedule I and II drugs.
−Removed: However, despite the foregoing reduced risk of abuse from Schedule III drugs, when compared to Schedule II drugs, there is no assurance that such reduced risk can be demonstrated in well controlled non-clinical and/or clinical studies in models of physical dependence, psychic
−Removed: dependence, addiction or precipitated withdrawal, or in studies of addiction or abuse liability in addicts, ex-addicts or recreational drug users.
+Added: However, despite the foregoing reduced risk of abuse from Schedule III drugs, when compared to Schedule II drugs, there is no assurance that such reduced risk can be demonstrated in well controlled non-clinical and/or clinical studies in models of physical dependence, psychic dependence, addiction or precipitated withdrawal, or in studies of addiction or abuse liability in addicts, ex-addicts or recreational drug users.
In the event that a reduced risk of abuse from Schedule III drugs, when compared to Schedule II drugs, is demonstrated in well controlled non- clinical and/or clinical studies, there is no assurance that the FDA will agree to incorporation of such favorable language in the products prescribing information.
5 unchanged sentences
We may need to focus our future efforts in new therapeutic areas where we have little or no experience.
−Removed: Although our primary strategic interests are in the areas of depression and COVID-19 therapies, ZYESAMI and NRX-101 have potential benefits in other therapeutic areas.
−Removed: If our drug development efforts in bipolar depression fails, or if the competitive landscape or investment climate for antidepressant drug development or COVID-19 therapies is less attractive, we may need to change our strategic focus to include development of our product candidates, or of newly acquired product candidates, for therapeutic areas other than depression and COVID-19.
−Removed: We have very limited drug development experience in other therapeutic areas and we may be unsuccessful in making this change to a company with a focus in areas other than depression and COVID-19 or a company with a focus in multiple therapeutic areas including depression and COVID-19.
+Added: Although our primary strategic interests are in the areas of depression therapies, NRX-101 has potential benefits in other therapeutic areas.
+Added: If our drug development efforts in bipolar depression fails, or if the competitive landscape or investment climate for antidepressant drug development therapies is less attractive, we may need to change our strategic focus to include development of our product candidates, or of newly acquired product candidates, for therapeutic areas other than depression.
+Added: We have very limited drug development experience in other therapeutic areas and we may be unsuccessful in making this change to a company with a focus in areas other than depression or a company with a focus in multiple therapeutic areas including depression.
Some of our products for clinical trials may be manufactured outside the U.S.
−Removed: Currently, our new clinical trial supplies for NRX-101 and ZYESAMI are being manufactured in the U.S.
+Added: Currently, our new clinical trial supplies for NRX-101 are being manufactured in the U.S.
, though some supplies are sourced from outside the U.S .
19 unchanged sentences
If our manufacturers cannot successfully produce material that conforms to our specifications and the FDA’s strict regulatory requirements, they will not be able to secure FDA approval for their manufacturing facilities.
−Removed: If the FDA does not approve these facilities for the commercial manufacture, we will need to find alternative suppliers, which would result in significant delays in obtaining FDA approvals.
+Added: If the FDA does not approve these facilities for the commercial manufacture, we will need to find alternative suppliers, which would
+Added: result in significant delays in obtaining FDA approvals.
These challenges may have a material adverse impact on our business, results of operations, financial condition and prospects.
Risks Related to Intellectual Property
−Removed: Our formulation of ZYESAMI is not covered by an issued patent and may be subject to future generic competition.
−Removed: The use of vasoactive intestinal peptide (“VIP”) in a buffer at acidic pH 6.4-7 to treat respiratory and other illnesses was patented by Profs.
−Removed: Sami Said and Victor Mutt in 1975 (US 4,016,258), with additional patents granted (US 4,113,711, US 4,119,618, US 4,220,642), all of which have expired.
−Removed: We have licensed the knowhow, trade secrets, and other intellectual property developed by Professor Said from the Research Foundation for the State University of New York (“RFSUNY”).
−Removed: The proprietary formulation, manufacturing method, and container closure system we have developed achieves commercially- acceptable stability of ZYESAMI.
−Removed: This work has led to the filing of U.S.
−Removed: Provisional Patent Application No.
−Removed: 63/295,058, which was filed in the USPTO on December 30, 2021, and to the filing of Utility Patent Application No.
−Removed: 17/574,753 with the USPTO on January 24, 2022, but there is no assurance that claims will be granted under these applications.
−Removed: In the event that no patent protection is granted covering the formulation of ZYESAMI, if the drug is approved by the FDA, it is anticipated to receive at least five (5) years of data exclusivity from the FDA under what is commonly known as “paragraph 4” protections.
−Removed: Should no patents be granted by the end of this data exclusivity period, competitors may be able to market generic versions of ZYESAMI.
Our business relies on certain licensing rights that can be terminated in certain circumstances.
2 unchanged sentences
In the event that the terms and conditions are not met, the licenses are at risk of being revoked and the granting process may be terminated.
−Removed: The primary license agreements include the Development and License Agreement, as amended, between Glytech LLC (“Glytech”) and NeuroRx (the “Glytech DLA”), the Exclusive License Agreement, dated as of April 16, 2019, by and between NeuroRx and Sarah Herzog Memorial Hospital Ezrat Nashim, the License and Option Agreement, dated as of September 1, 2020, between RFSUNY and NeuroRx, and the Collaboration Agreement .
−Removed: Although ZYESAMI does not rely on U.S.
−Removed: Patent 8178489B2 or any other intellectual property of Relief Therapeutics, the intellectual property licensed to us under the Collaboration Agreement may also be at risk if the recent Complaint filed by Relief Therapeutics cannot be amicably resolved by the parties through mediation.
+Added: The primary license agreements include the Development and License Agreement, as amended, between Glytech LLC (“Glytech”) and NeuroRx (the “Glytech DLA”) and the Exclusive License Agreement, dated as of April 16, 2019, by and between NeuroRx and Sarah Herzog Memorial Hospital Ezrat Nashim.
We may require additional licensing rights in the future, which may not be attainable.
Our ability to fully develop the full commercial potential of our product candidates may require us to acquire additional licensing rights from third parties in the future.
−Removed: There are no assurances that such rights will be available in the
−Removed: market when required, or that an agreement could be reached to license such rights from a third party on terms acceptable to us.
+Added: There are no assurances that such rights will be available in the market when required, or that an agreement could be reached to license such rights from a third party on terms acceptable to us.
We may not succeed at in-licensing drug candidates or technologies to expand our product pipeline.
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it is possible that none of our pending patent applications or the pending patent applications of our licensors will result in issued patents;
−Removed: our issued patents and issued patents of our licensors may not provide a basis for commercially viable technologies, or may not provide us with any competitive advantages, or may be challenged and invalidated by third parties;
+Added: our issued patents and issued patents of our licensors may not provide a basis for commercially viable technologies, or may not provide us with any
+Added: competitive advantages, or may be challenged and invalidated by third parties;
and, we may not develop additional proprietary technologies that are patentable.
9 unchanged sentences
The cost of enforcing our patent rights against infringers, if such enforcement is required, could be significant, and we do not currently have the financial resources to fund such litigation.
−Removed: Further, such litigation can go on for years and the time demands could interfere
−Removed: with our normal operations and may absorb significant management time.
+Added: Further, such litigation can go on for years and the time demands could interfere with our normal operations and may absorb significant management time.
There has been substantial litigation and other proceedings regarding patent and other intellectual property rights in the pharmaceutical industry.
15 unchanged sentences
While a patent gives the holder this right to exclude others, it is not an authorization to commercialize the invention, where other permissions may be required for permissible commercialization to occur.
−Removed: For example, a drug cannot be marketed without the appropriate authorization from the FDA, regardless of the existence of a patent covering the product.
+Added: For example, a drug cannot be marketed without the appropriate authorization from
+Added: the FDA, regardless of the existence of a patent covering the product.
Further, the invention, even if patented itself, may not be able to be successfully commercialized if it infringes the valid patent rights of another party.
5 unchanged sentences
In addition, we may have to expend resources to protect our interests from possible infringement by others.
−Removed: If we are unable to obtain the statutory patent extension related to the review time in the U.S., we may need to rely on the 3-year Hatch-Waxman Act marketing exclusivity, the six month pediatric exclusivity, any approved -year Orphan Drug exclusivities, potential future formulation patents and up to ten years of data exclusivity in Europe.
+Added: If we are unable to obtain the statutory patent extension related to the review time in the U.S., we may need to rely on the 3-year Hatch-Waxman Act marketing exclusivity, the six-month pediatric exclusivity, any approved Orphan Drug exclusivities, potential future formulation patents and up to ten years of data exclusivity in Europe.
See “ Risks Related to Clinical and Regulatory Matters — We may not be able to obtain Hatch-Waxman Act marketing exclusivity or equivalent regulatory data exclusivity protection in other jurisdictions for our products .”
13 unchanged sentences
We do not have the ability to independently conduct all the pre-clinical and clinical trials for our products and we must rely on third parties, such as contract research organizations, medical institutions, clinical investigators and contract laboratories to conduct such trials.
−Removed: If these third parties do not successfully carry out their contractual duties or regulatory obligations or meet expected deadlines, if these third parties need to be replaced, or if the quality or accuracy of the data they obtain is compromised due to the failure to adhere to our clinical protocols or regulatory requirements or for other reasons, our pre-clinical development activities or clinical trials may be extended, delayed, suspended or terminated, and we may not be able to obtain regulatory approval for, or successfully commercialize, our products on a timely basis, if at all, and our business, operating results and prospects may be adversely affected.
+Added: If these third parties do not successfully carry out their contractual duties or regulatory obligations or meet expected deadlines, if these third parties need to be replaced, or if the quality or accuracy of the data they obtain is compromised due to the failure to adhere to our clinical protocols or regulatory requirements or for other reasons, our pre-clinical development activities or clinical trials may be extended, delayed, suspended or terminated, and
+Added: we may not be able to obtain regulatory approval for, or successfully commercialize, our products on a timely basis, if at all, and our business, operating results and prospects may be adversely affected.
Furthermore, our third-party clinical trial investigators may be delayed in conducting our clinical trials for reasons outside of their control.
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In addition, establishing such operations will take time and involve significant expense.
−Removed: If we decide to enter into new co-promotion or other licensing arrangements with third parties, we may be unable to locate acceptable collaborators because the number of potential collaborators is limited and because of competition from
−Removed: others for similar alliances with potential collaborators.
+Added: If we decide to enter into new co-promotion or other licensing arrangements with third parties, we may be unable to locate acceptable collaborators because the number of potential collaborators is limited and because of competition from others for similar alliances with potential collaborators.
Even if we are able to identify one or more acceptable new collaborators, we may not be able to enter into any collaborative arrangements on favorable terms, or at all.
13 unchanged sentences
See the “Description of Capital Stock” section of this annual report.
−Removed: The issuance of earnout shares would increase the number of shares eligible for future resale in the public market and result in dilution to our stockholders.
−Removed: Upon satisfaction of certain triggering events, an aggregate of 25,000,000 shares of our Common Stock may be issued as earnout shares.
−Removed: The earnout threshold is achieved if, prior to December 31, 2022, ZYESAMI receives EUA by the FDA and we submit, and the FDA files for review, an NDA for ZYESAMI.
−Removed: The earnout shares will be issued within five (5) business days of achieving the earnout threshold.
−Removed: To the extent such earnout shares are issued, additional shares of our Common Stock will be issued, which will result in dilution to the holders of our Common Stock and increase the number of shares eligible for resale in the public market.
−Removed: Sales of substantial numbers of such shares in the public market could adversely affect the market price of our Common Stock.
Future sales, or the perception of future sales, of our Common Stock by us or our existing stockholders in the public market could cause the market price for our Common Stock to decline.
The sale of substantial amounts of shares of our Common Stock in the public market, or the perception that such sales could occur, could harm the prevailing market price of shares of our Common Stock.
−Removed: These sales, or the possibility that these sales may occur, also might make it more difficult for us to sell equity securities in the future at a time and at a price that we deem appropriate.
+Added: These sales, or the possibility that
+Added: these sales may occur, also might make it more difficult for us to sell equity securities in the future at a time and at a price that we deem appropriate.
In addition, the shares of Common Stock reserved for future issuance under the NRx 2021 Omnibus Incentive Plan (the “Incentive Plan”) are eligible for sale in the public market once those shares are issued, subject to provisions relating to various vesting agreements, lock-up agreements and, in some cases, limitations on volume and manner of sale applicable to affiliates under Rule 144 of the Exchange Act, as applicable.
−Removed: The number of shares reserved for future issuance under the Incentive Plan is 5,373,049.
+Added: The original number of shares reserved for future issuance under the Incentive Plan was 5,373,394.
In addition, the Incentive Plan includes an evergreen feature that will allow our Board, in its sole discretion, to reserve additional shares of Common Stock for future issuance under the Incentive Plan each calendar year, beginning January 1, 2022 and ending on and including January 1, 2031, equal to the lesser of (A) 1% of the shares of Common Stock outstanding on the final day of the immediately preceding calendar year or (B) a smaller number of shares determined by the Board.
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Sales of substantial amounts of Common Stock, or the perception that such sales could occur, may adversely affect prevailing market prices of our Common Stock or warrants.
−Removed: We qualify as an “emerging growth company” as well as a “smaller reporting company” within the meaning of the Securities Act, and if we take advantage of certain exemptions from disclosure requirements available to emerging growth companies or smaller reporting companies, it could make our securities less attractive to investors and may make it more difficult to compare our performance to the performance of other public companies.
−Removed: We qualify as an “emerging growth company” as defined in Section 2(a)(19) of the Securities Act of 1933, as amended (the “Securities Act”), as modified by the JOBS Act.
−Removed: As such, we will be eligible for and intend to take advantage of certain exemptions from various reporting requirements applicable to other public companies that are not emerging growth companies for as long as it continues to be an emerging growth company, including (a) the exemption from the auditor attestation requirements with respect to internal control over financial reporting under Section 404(b) of the Sarbanes-Oxley Act, (b) the exemptions from say-on-pay, say-on-frequency and say-on-golden parachute voting requirements and (c) reduced disclosure obligations regarding executive compensation in its periodic reports and proxy statements.
−Removed: We will remain an emerging growth company until the earliest of (i) the last day of the fiscal year in which the market value of our Common Stock that is held by non-affiliates exceeds $700 million as of June 30 of that fiscal year, (ii) the last day of the fiscal year in which we have total annual gross revenue of $1.07 billion or more during such fiscal year (as indexed for inflation), (iii) the date on which we have issued more than $1 billion in non-convertible debt in the prior three-year period or (iv) the last day of the fiscal year following the fifth anniversary of the date of the first sale of Common Stock in the BRPA initial public offering (for purposes of this clause (iv), this date is December 31, 2022).
−Removed: In addition, Section 107 of the JOBS Act also provides that an emerging growth company can take advantage of the exemption from complying with new or revised accounting standards provided in Section 7(a)(2)(B) of the Securities Act as long as we are an emerging growth company.
−Removed: An emerging growth company can therefore delay the adoption of certain accounting standards until those standards would otherwise apply to private companies.
−Removed: We have elected not to opt out of such extended transition period and, therefore, we may not be subject to the same new or revised accounting
−Removed: standards as other public companies that are not emerging growth companies.
−Removed: Investors may find Common Stock less attractive because we will rely on these exemptions, which may result in a less active trading market for the Common Stock and its price may be more volatile.
−Removed: Additionally, we will qualify as a “smaller reporting company” as defined in Item 10(f)(1) of Regulation S-K.
+Added: We qualify as a “smaller reporting company” within the meaning of the Securities Act, and if we take advantage of certain exemptions from disclosure requirements available to smaller reporting companies, it could make our securities less attractive to investors and may make it more difficult to compare our performance to the performance of other public companies.
+Added: We qualify as a “smaller reporting company” as defined in Item 10(f)(1) of Regulation S-K.
Smaller reporting companies may take advantage of certain reduced disclosure obligations, including, among other things, providing only two (2) years of audited financial statements.
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Additionally, Section 22 of the Securities Act creates concurrent jurisdiction for federal and state courts over all suits brought to enforce any duty or liability created by the Securities Act or the rules and regulations thereunder.
−Removed: As noted above, the Charter and the Bylaws will provide that the federal district courts of the U.S.
+Added: As noted above,
+Added: the Charter and the Bylaws will provide that the federal district courts of the U.S.
shall have jurisdiction over any action arising under the Securities Act.
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Accordingly, for such period of time, Jonathan Javitt and Daniel Javitt will have significant influence with respect to our management, business plans and policies.
−Removed: In particular, for so long as Jonathan Javitt and Daniel Javitt continue to own a significant percentage of Common Stock, Jonathan Javitt and Daniel Javitt will be able to cause or prevent a change of control of NRx or a change in the composition of our Board and could preclude any unsolicited acquisition of NRx.
+Added: In particular, for so long as Jonathan Javitt and Daniel Javitt continue to own a significant percentage of Common Stock, Jonathan Javitt and Daniel Javitt will be able to influence the composition of our Board and could preclude any unsolicited acquisition of NRx.
The concentration of ownership could deprive you of an opportunity to receive a premium for your shares of Common Stock as part of a sale of NRx and ultimately might affect the market price of Common Stock.
So long as Jonathan Javitt and Daniel Javitt continue to own a significant amount of our combined voting power, even if such amount is less than 50%, Jonathan Javitt and Daniel Javitt will continue to be able to strongly influence or effectively control our decisions.
−Removed: Notwithstanding Jonathan Javitt’s and Daniel Javitt’s or substantial influence over NRx, we may from time to time enter into transactions with Jonathan Javitt and Daniel Javitt and their respective affiliates, or enter into transactions in which Jonathan Javitt and Daniel Javitt or their respective affiliates otherwise have a direct or indirect material interest.
+Added: Notwithstanding Jonathan Javitt’s and Daniel Javitt’s substantial influence over NRx, we may from time to time enter into transactions with Jonathan Javitt and Daniel Javitt and their respective affiliates, or enter into transactions in which Jonathan Javitt and Daniel Javitt or their respective affiliates otherwise have a direct or indirect material interest.
We have adopted a formal written policy for the review and approval of transactions with related persons.
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We are no longer a “controlled company” under the corporate governance rules of Nasdaq.
−Removed: However, during the applicable phase-in periods we may continue to rely on exemptions from certain corporate governance standards, which limit the presence of independent directors on our Board or committees of the Board.
+Added: However, we continue to rely on an exception in the listing requirements to allow a non-independent director to sit on the Nominating and Governance Committee.
Previously, Jonathan Javitt and Daniel Javitt controlled the votes of the majority of our Common Stock.
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We are no longer a “controlled company” under the corporate governance rules of Nasdaq.
−Removed: Under the Nasdaq listing requirements, a company that ceases to be a “controlled company” must comply with the independent board committee requirements as they relate to the nominating and corporate governance and compensation committees no later than the following phase-in schedule:
−Removed: (1) one independent committee member at the time it ceases to be a controlled company, (2) a majority of independent committee members within 90 days of the date it ceases to be a controlled company and (3) all independent committee members within one year of the date it ceases to be a controlled company.
−Removed: Additionally, the Nasdaq listing requirements provide a 12-month phase-in period from the date a company ceases to be a “controlled company” to comply with the majority independent board requirement.
−Removed: At this time, the majority of our directors are independent, as are a majority of the members of each of our committees while the nominating and corporate governance committee is not made up solely of independent directors.
−Removed: Until we are fully subject to these requirements, however, our stockholders will not have the same protections afforded to stockholders of companies that are subject to all of the corporate governance requirements of Nasdaq.
+Added: Under the Nasdaq listing requirements, a company that ceases to be a “controlled company” must comply with the independent board committee
+Added: requirements as they relate to the nominating and corporate governance.
+Added: However, we continue to rely on Rule 5605(e)(3), which permits that one director, who is not an independent director and is not currently an executive officer or employee of the Company, may be appointed to the nominating and governance committee if the board, under exceptional and limited circumstances, determines that such individual's membership on the committee is required by the best interests of the Company and its Shareholders.
+Added: Jonathan Javitt, who is not an independent director, continues to serve on the Company’s nominating and corporate governance committee because the Board has determined that his unique experience and qualifications as a scientist and a co-founder of the Company are beneficial to the Company.
+Added: Until we are fully subject to the listing requirements, however, our stockholders will not have the same protections afforded to stockholders of companies that are subject to all of the corporate governance requirements of Nasdaq.
General Risk Factors
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You may not be able to resell your shares at an attractive price due to a number of factors such as those listed in “— Risks Related to Our Business and Industry ” and the following:
−Removed: • the impact of the COVID-19 pandemic on our financial condition and the results of operations;
+Added: • the impact of a resurgence of the COVID-19 pandemic on our financial condition and the results of operations;
• our operating and financial performance and prospects;
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• the public’s reaction to our press releases, other public announcements and filings with the SEC;
−Removed: • the market’s reaction to our reduced disclosure and other requirements as a result of being an “emerging growth company” under the JOBS Act;
• the size of our public float;
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The trading market for our Common Stock will depend in part on the research and reports that third-party securities analysts publish about us and the industries in which we operate.
−Removed: We may be unable or slow to attract research coverage and if one or more analysts cease coverage of us, the price and trading volume of our securities would likely be negatively impacted.
+Added: We may be unable, or slow, to attract and maintain research coverage and if one or more analysts cease coverage of us, the price and trading volume of our securities would likely be negatively impacted.
If any of the analysts that may cover us change their recommendation regarding our securities adversely, or provide more favorable relative recommendations about our competitors, the price of our securities would likely decline.
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In addition, as a public company, we are required to document and test our internal control over financial reporting pursuant to Section 404 of the Sarbanes-Oxley Act so that our management can certify as to the effectiveness of our internal control over financial reporting.
−Removed: As an emerging growth company, we will not be required to comply with the auditor attestation requirements of Section 404 of the Sarbanes- Oxley Act.
For additional information related to the risks and uncertainties of our compliance with the Sarbanes-Oxley Act, see “ Risk Related to an Early-Stage Company — Failure to achieve and maintain effective internal controls over financial reporting in accordance with Section 404 of the Sarbanes-Oxley Act could impair our ability to produce timely and accurate financial statements or comply with applicable regulations and have a material adverse effect on our business.”
+Added: If we fail to meet the applicable continued listing requirements of NASDAQ Global Market, NASDAQ may delist our common stock, in which case the liquidity and market price of our common stock could decline.
+Added: Our common stock is currently listed on the NASDAQ Global Market.
+Added: In order to maintain that listing, we must satisfy certain continued listing requirements.
+Added: including the requirement that our Common Stock maintain an average minimum bid price of $1.00.
+Added: Since March 1, 2023, the closing sale price of our Common Stock as reported on Nasdaq has been less than $1.00.
+Added: In the past, we have received a deficiency letter from Nasdaq for failing to maintain a minimum bid price of $1.00, but we have since regained compliance.
+Added: If we are deficient in maintaining the necessary listing requirements, our common stock may be delisted.
+Added: If our stock is delisted, an active trading market for our common stock may not be sustained and the market price of our common stock could decline.
+Added: Market price of our Common Stock may be volatile, which could subject us to securities class action litigation and result in substantial losses for our stockholders.
+Added: The market price of shares of our Common Stock could be subject to wide fluctuations in response to many risk factors listed in this section and the documents incorporated by reference in this prospectus supplement and the accompanying prospectus as well as other factors others beyond our control.
+Added: Furthermore, the stock markets have experienced extreme price and volume fluctuations that have affected and continue to affect the market prices of equity securities of many companies.
+Added: These fluctuations often have been unrelated or disproportionate to the operating performance of those companies.
+Added: These broad market and industry fluctuations as well as general economic, political and market conditions, such as recessions, interest rate changes or international currency fluctuations, may negatively impact the market price of shares of our Common Stock.
+Added: In addition, such fluctuations could subject us to securities class action litigation, which could result in substantial costs and divert our management’s attention from other business concerns, which could potentially harm our business.
+Added: As a result of this volatility, our stockholders may not be able to sell their shares of our Common Stock at or above the price at which they purchased their shares of our Common Stock.
We do not intend to pay dividends on our Common Stock for the foreseeable future.
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Compared sentence by sentence after normalising whitespace, quotation marks, case and digits, so re-formatting and restated figures do not read as changed language. Wording changes appear as one removal and one addition. The current filing and the prior one are authoritative.