2 unchanged sentences
Any of these factors, in whole or in part, could materially and adversely affect our business, financial condition, results of operations, and stock price.
−Removed: The following information should be read in conjunction with Part I, Item 2, “Management’s Discussion and Analysis of Financial Condition and Results of Operations” and the consolidated financial statements and related notes in Part I, Item 1, “Financial Statements” of this Annual Report .
+Added: The following information should be read in conjunction with Part II, Item 7, “Management’s Discussion and Analysis of Financial Condition and Results of Operations” and the consolidated financial statements and related notes in Part II, Item 8, “Financial Statements and Supplementary Data” of this Annual Report.
+Added: Risk Factor Summary
+Added: Investing in our Common Stock involves a high degree of risk because our business is subject to numerous risks and uncertainties, as fully described below.
+Added: The principal factors and uncertainties that make investing in our Common Stock risky include, among others :
+Added: • We will need to raise additional capital, and if we are unable to do so when needed, we will not be able to continue as a going concern.
+Added: • We have historically incurred losses, have a limited operating history on which to assess our business, and anticipate that we will continue to incur significant losses for the foreseeable future.
+Added: Table of Con t ents
+Added: • We have never generated any revenue from product sales and may never be profitable.
+Added: • Raising additional capital may cause dilution to our stockholders, restrict our operations, or require us to relinquish rights.
+Added: • Clinical trials are costly, time consuming, and inherently risky, and we may fail to demonstrate safety and efficacy to the satisfaction of applicable regulatory authorities.
+Added: • Our product candidates may cause undesirable side effects or have other properties that could delay or prevent their regulatory approval, limit the commercial viability of an approved label, or result in significant negative consequences following marketing approval, if any.
+Added: • We are heavily dependent on the success of our product candidates, which are in the early stages of clinical development.
+Added: Some of our product candidates have produced results only in non-clinical settings, or for other indications than those for which we contemplate conducting development and seeking FDA approval, and we cannot give any assurance that we will generate data for any of our product candidates sufficiently supportive to receive regulatory approval in our planned indications, which will be required before they can be commercialized.
+Added: • Product development involves a lengthy and expensive process with an uncertain outcome, and results of earlier preclinical studies and clinical trials may not be predictive of future clinical trial results.
Risks Related to Our Financial Condition and Capital Requirements
+Added: There is no guarantee that our acquisition of Private Viridian will increase stockholder value.
+Added: In October 2020, we acquired Private Viridian.
+Added: We cannot guarantee that implementing the acquisition and related transactions will not impair stockholder value or otherwise adversely affect our business.
+Added: The acquisition poses significant integration challenges between our businesses and management teams which could result in management and business disruptions, any of which could harm our results of operation, business prospects, and impair the value of such acquisition to our stockholders.
We will need to raise additional capital, and if we are unable to do so when needed, we will not be able to continue as a going concern.
−Removed: This Annual Report includes disclosures regarding our management’s assessment of our ability to continue as a going concern.
−Removed: As of December 31, 2019 , we had $26.8 million of cash, cash equivalents, and short-term investments, and we had $7.7 million of outstanding debt principal obligations under our note payable to Silicon Valley Bank.
−Removed: Based on our current operating plan, we believe our current resources, after giving effect to the proceeds received in sales of our common stock subsequent to December 31, 2019 and through the date of this Annual Report, will be sufficient to fund our operations and allow us to meet our liquidity needs into the third quarter of 2021 .
−Removed: As a result, we will need to raise additional capital to fund our operations and service our debt obligations.
+Added: As of December 31, 2020, we had $127.6 million of cash, cash equivalents, and short-term investments.
+Added: We expect that our current resources will enable us to fund our operating expenses and capital expenditure requirements into the second half of 2023.
+Added: We will need to raise additional capital to continue to fund our operations and service our obligations in the future.
If we are unable to raise additional capital when needed, we will not be able to continue as a going concern.
9 unchanged sentences
• seek strategic alliances, or amend existing alliances, for research and development programs at an earlier stage than otherwise would be desirable or that we otherwise would have sought to develop independently, or on terms that are less favorable than might otherwise be available in the future;
+Added: Table of Con t ents
• dispose of technology assets, or relinquish or license on unfavorable terms, our rights to technologies or any of our product candidates that we otherwise would seek to develop or commercialize ourselves;
1 unchanged sentence
• file for bankruptcy or cease operations altogether.
−Removed: For instance, in 2019 we began implementing two phases of a cost restructuring plan to streamline the organization, reduce costs, and direct resources to advance cobomarsen and miR-29 mimics, including remlarsen and MRG-229, while reducing investments in new discovery research.
−Removed: The restructuring plan identified approximately 44 positions for elimination, or approximately 50% of our total workforce, primarily associated with research and development and corresponding project, general, and administrative support.
−Removed: If we are unable to raise additional capital, we may be forced to undergo additional restructuring efforts or cease some or all of our operations altogether.
Any of these events could have a material adverse effect on our business, operating results, and prospects.
Additionally, any capital raising efforts are subject to significant risks and contingencies, as described in more detail under the risk factor titled “Raising additional capital may cause dilution to our stockholders, restrict our operations, or require us to relinquish rights.”
−Removed: In the past, our management has concluded that, due to our need for additional capital and the uncertainties surrounding our ability to raise such funding, substantial doubt existed as to our ability to continue as a going concern, and our management may make a similar determination in the future.
−Removed: In the past, our management has concluded that, due to our need for additional capital and the uncertainties surrounding our ability to raise such funding, substantial doubt existed as to our ability to continue as a going concern.
−Removed: Though our management has not made such a conclusion as of December 31, 2019, we cannot predict whether our management will make a similar determination regarding our ability to continue as a going concern in the future.
−Removed: Changing circumstances may cause us to consume capital significantly faster or slower than we currently anticipate.
−Removed: If, in the future, we are delayed in completing or are unable to complete additional funding and/or a strategic transaction, we may discontinue our development activities or operations, but there are no assurances that these actions would be sufficient to allow us to continue to operate as a going concern.
−Removed: Therefore, even if we resolve this uncertainty, our independent registered public accountants and/or management could conclude that uncertainty as to our ability to continue as a going concern could exist at a future date.
We have historically incurred losses, have a limited operating history on which to assess our business, and anticipate that we will continue to incur significant losses for the foreseeable future.
−Removed: We are a clinical-stage biopharmaceutical company with a limited operating history.
+Added: We are a biotechnology company with a limited operating history.
We have historically incurred net losses.
During the years ended December 31, 2020 and 2019, net loss was $110.7 million and $41.9 million, respectively.
−Removed: As of December 31, 2019 , we had an accumulated deficit of $168.2 million .
−Removed: As of December 31, 2019 , we had cash and cash equivalents of $24.8 million and short-term investments of $2.0 million .
−Removed: In March 2017, we entered into an at the market issuance Common Stock Sales Agreement, or the ATM Agreement, with Cowen and Company, LLC, or Cowen, under which we may offer and sell, from time to time, at our sole discretion, shares of our common stock having an aggregate offering price of up to $50.0 million through Cowen as our sales agent.
−Removed: Through March 13, 2020 , we had sold, pursuant to the terms of the ATM Agreement, 1,871,386 shares of our common stock for aggregate net proceeds of approximately $11.0 million after deducting initial expenses for executing the “at the market offering” and commissions to Cowen as sales agent.
−Removed: In February 2018, we entered into an underwriting agreement, or the 2018 Underwriting Agreement, with Jefferies LLC, Evercore Group L.L.C., and Deutsche Bank Securities Inc., as representatives of the several underwriters, relating to our 2018 public offering.
−Removed: Pursuant to the 2018 Underwriting Agreement, in February 2018 we sold 7,414,996 shares of our common stock, which resulted in net proceeds of approximately $37.9 million after deducting underwriting commissions and discounts and other offering expenses payable by us.
−Removed: In August 2018 , we entered into a Common Stock Purchase Agreement, or the LLS Stock Purchase Agreement, with the Leukemia and Lymphoma Society, or LLS, for the sale of up to $5.0 million of shares of our common stock, or the LLS Offering, to LLS and its affiliates under the LLS Purchase Agreement.
−Removed: In October 2019, the LLS Stock Purchase Agreement was assigned by LLS to LLS TAP.
−Removed: Through March 13, 2020 , we had issued an aggregate of 757,351 shares of our common stock to LLS and its affiliates in the LLS Offering, for aggregate net proceeds of approximately $1.4 million , after deducting expenses incurred in connection with the LLS Offering.
−Removed: As a result of the modifications of the SOLAR trial we announced in December 2019, we do not anticipate meeting the milestones under the LLS Stock Purchase Agreement and as such, do not expect we will receive the remaining proceeds available under the LLS Stock Purchase Agreement unless the agreement is amended, which we can provide no assurances will occur.
−Removed: In December 2019, we entered into a Common Stock Purchase Agreement, or the Aspire Agreement, with Aspire Capital Fund, LLC, an Illinois limited liability company, or Aspire Capital.
−Removed: Pursuant to this agreement, we may issue up to $20.0 million of shares of our common stock from time to time.
−Removed: Through March 13, 2020 , we had issued an aggregate of 4,757,544 shares of common stock under the Aspire Agreement, which amount includes (i) 959,079 shares of common stock issued to Aspire Capital as consideration for its commitment to purchase shares of our common stock under the Aspire Agreement, (ii) 1,598,465 shares of common stock issued to Aspire Capital for an aggregate sale price of $1.0 million as an initial purchase under the Aspire Agreement, or the Initial Purchase Shares, and (iii) 2,200,000 shares of common stock issued to Aspire Capital for an aggregate sale price of $4.1 million as purchase shares under the terms of the Aspire Agreement.
−Removed: In February 2020, we entered into an underwriting agreement, or the 2020 Underwriting Agreement with Oppenheimer & Co.
−Removed: Inc., as sole underwriter, or the Underwriter, relating to our 2020 public offering, or the 2020 Public Offering.
−Removed: Pursuant to the 2020 Underwriting Agreement, the Underwriter purchased 15,000,000 shares of our common stock and warrants to purchase 7,500,000 shares of our common stock.
−Removed: Each whole warrant has an exercise price of $1.10 per share, was exercisable immediately and expires on the fifth anniversary of the date of issuance.
−Removed: Though the shares of common stock and warrants were sold together as a fixed combination, each consisting of one share of our common stock and one-half warrant, with each whole warrant exercisable to purchase one whole share of our common stock, the shares of our common stock and warrants were issued separately and were immediately separable upon issuance.
−Removed: The combined price to the public in the 2020 Public Offering for each share of common stock and accompanying one-half warrant was $1.00 , which resulted in approximately $14.0 million of net proceeds to us after deducting underwriting commissions and discounts and other estimated offering expenses payable by us and excluding the proceeds, if any, from the exercise of the warrants.
−Removed: We believe that we have sufficient capital, after giving effect to the proceeds received in sales of our common stock subsequent to December 31, 2019 and through the date of this Annual Report, to fund our operations in the normal course of business in order to meet our liquidity needs into the third quarter of 2021 .
−Removed: We will continue to require substantial additional capital to continue our preclinical and clinical development and potential commercialization activities.
−Removed: Accordingly, we will need to raise substantial additional capital to continue to fund our operations.
−Removed: The amount and timing of our future funding requirements will depend on many factors, including the pace and results of our clinical development efforts.
+Added: As of December 31, 2020, we had an accumulated deficit of $278.9 million and cash, cash equivalents, and short-term investments of $127.6 million.
+Added: We expect that our current resources will enable us to fund our operating expenses and capital expenditure requirements into the second half of 2023.
+Added: We will need to raise substantial additional capital to continue to fund our operations in the future.
+Added: The amount and timing of our future funding requirements will depend on many factors, including the pace and results of our clinical development efforts and the long-term effects of the COVID-19 pandemic.
+Added: In March 2020, the World Health Organization declared the outbreak of COVID-19 a global pandemic.
+Added: This outbreak is causing major disruptions to businesses and markets worldwide as the virus spreads.
+Added: The economic uncertainty surrounding the COVID-19 pandemic may dramatically reduce our ability to secure debt or equity financing necessary to support our operations.
+Added: We are unable to currently estimate the financial effect of the pandemic.
+Added: If the pandemic continues to be a severe worldwide crisis, it could have a material adverse effect on our business, results of operations, financial condition, and cash flows.
Failure to raise capital as and when needed, on favorable terms or at all, would have a negative impact on our financial condition and our ability to develop our product candidates.
1 unchanged sentence
If we are unable to acquire additional capital or resources, we will be required to modify our operational plans to complete future milestones.
−Removed: For instance, in 2019 we began implementing two phases of a cost restructuring plan to streamline the organization, reduce costs, and direct resources to advance cobomarsen and miR-29 mimics, including remlarsen and MRG-229, while reducing investments in new discovery research.
−Removed: The restructuring plan identified approximately 44 positions for elimination, or approximately 50% of our total workforce, primarily associated with research and development and corresponding project, general, and administrative support.
We have based these estimates on assumptions that may prove to be wrong, and we could exhaust our available financial resources sooner than we currently anticipate.
10 unchanged sentences
We expect to continue to incur significant expenses and increasing operating losses for the foreseeable future and our expenses will increase substantially if and as we:
−Removed: continue the clinical development of our product candidates;
+Added: Table of Con t ents
+Added: • continue the development of our product candidates;
• continue efforts to discover and develop new product candidates;
• continue the manufacturing of our product candidates or increase volumes manufactured by third parties;
−Removed: advance our programs into larger, more expensive clinical trials;
+Added: • advance our programs into large expensive clinical trials;
• initiate additional preclinical studies or clinical trials for our product candidates;
21 unchanged sentences
• obtaining coverage and adequate reimbursement from third-party payors and maintaining pricing for our product candidates that supports profitability;
+Added: Table of Con t ents
• attracting, hiring, and retaining qualified personnel.
2 unchanged sentences
We will also have to develop or acquire manufacturing capabilities or continue to contract with contract manufacturers in order to continue development and potential commercialization of our product candidates.
−Removed: For instance, if the costs of manufacturing our drug product are not commercially feasible, we will need to develop or procure our drug product in a commercially feasible manner in order to successfully commercialize any future approved product, if any.
+Added: For instance, if the costs of manufacturing our drug product are not commercially feasible, we will need to develop or procure our drug product in a commercially feasible manner in order to successfully commercialize a future approved product, if any.
Additionally, if we are not able to generate revenue from the sale of any approved products, we may never become profitable.
5 unchanged sentences
If we are unable to raise additional funds through equity or debt financings or other arrangements with third parties when needed, we may be required to delay, limit, reduce or terminate our product development or future commercialization efforts or grant rights to third parties to develop and market product candidates that we would otherwise prefer to develop and market ourselves.
−Removed: To the extent that we raise additional capital through the sale of equity, including pursuant to any sales under the ATM Agreement, the Aspire Agreement, the LLS Stock Purchase Agreement, convertible debt or other securities convertible into equity, the ownership interest of our stockholders will be diluted, and the terms of these new securities may include liquidation or other preferences that adversely affect the rights of our stockholders.
−Removed: For instance, through March 13, 2020 , we had sold (i) pursuant to the terms of the ATM Agreement, approximately 1,871,386 shares of our common stock for aggregate net proceeds of approximately $11.0 million , (ii) pursuant to the Aspire Agreement approximately 3,798,465 shares of our common stock for aggregate net proceeds of approximately $4.9 million , and (iii) pursuant to the LLS Stock Purchase Agreement approximately 757,351 shares of our common stock for aggregate net proceeds of approximately $1.4 million .
−Removed: After giving effect to these sales, we anticipate that we will continue to make sales of our common stock under the ATM Agreement and the Aspire Agreement from time to time into the foreseeable future, and we may sell shares of our common stock of up to $38.6 million and up to $14.9 million in additional aggregate value under the ATM Agreement and Aspire Agreement, respectively.
−Removed: As a result of the modifications of the SOLAR trial we announced in December 2019, we do not anticipate meeting the milestones under the LLS Stock Purchase Agreement and as such, do not expect we will receive the remaining $3.5 million in proceeds available under the LLS Stock Purchase Agreement unless the agreement is amended, which we can provide no assurances will occur.
−Removed: Sales under the ATM Agreement, the Aspire Agreement, or the LLS Stock Purchase Agreement dilute the ownership interest of our stockholders and may cause the price per share of our common stock to decrease.
−Removed: In connection with our 2020 Public Offering and in accordance with the terms of the 2020 Underwriting Agreement, we issued warrants to purchase up to 7,500,000 shares of our common stock.
−Removed: The warrants issued in the 2020 Public Offering, if exercised, will dilute the ownership interest of our stockholders and may cause the price per share of our common stock to decrease.
+Added: To the extent that we raise additional capital through the sale of equity, including pursuant to any sales under the Common Stock Sales Agreement entered into in March 2017 (“ATM Agreement”) with Cowen and Company, LLC (“Cowen”) or the Common Stock Purchase Agreement entered into in December 2019 (“Common Stock Purchase Agreement”) with Aspire Capital Fund LLC (“Aspire Capital”), convertible debt, or other securities convertible into equity, the ownership interest of our stockholders will be diluted, and the terms of these new securities may include liquidation or other preferences that adversely affect the rights of our stockholders.
+Added: Any additional sales of our Common Stock under the ATM Agreement and the Aspire Agreement will dilute the ownership interest of our stockholders and may cause the price per share of our Common Stock to decrease.
+Added: In February 2020, we entered into an Underwriting Agreement (“2020 Underwriting Agreement”) with Oppenheimer & Co.
+Added: (“Underwriter”).
+Added: Pursuant to the 2020 Underwriting Agreement, the Underwriter purchased 1,000,000 shares of our Common Stock and warrants to purchase 500,000 shares of our Common Stock (“2020 Public Offering”).
+Added: In accordance with the terms of the 2020 Underwriting Agreement, we issued warrants to purchase up to 500,000 shares of our Common Stock.
+Added: Warrants that remain outstanding, if exercised, will dilute the ownership interest of our stockholders and may cause the price per share of our Common Stock to decrease.
Debt financing, if available, would likely involve agreements that include covenants limiting or restricting our ability to take specific actions, such as incurring additional debt, making capital expenditures, making additional product acquisitions, or declaring dividends.
−Removed: For instance, our loan and security agreement with Silicon Valley Bank limits our ability to enter into an asset sale, enter into any change of control, incur additional indebtedness, pay any dividends, or enter into specified transactions with our affiliates.
−Removed: If we raise additional funds through strategic collaborations or licensing arrangements with third parties, we may have
−Removed: to relinquish valuable rights to our product candidates or future revenue streams or grant licenses on terms that are not favorable to us.
+Added: If we raise additional funds through strategic collaborations or licensing arrangements with third parties, we may have to relinquish valuable rights to our product candidates or future revenue streams or grant licenses on terms that are not favorable to us.
We cannot be assured that we will be able to obtain additional funding if and when necessary to fund our entire portfolio of product candidates to meet our projected plans.
If we are unable to obtain funding on a timely basis, we may be required to delay or discontinue one or more of our development programs or the commercialization of any product candidates or be unable to expand our operations or otherwise capitalize on potential business opportunities, which could materially harm our business, financial condition, and results of operations.
−Removed: We have also historically received funds directly or indirectly from state and federal government grants for research and development.
−Removed: The grants have been, and any future government grants and contracts we may receive may be, subject to the risks and contingencies set forth below under the risk factor titled “ Reliance on government funding for our programs may add uncertainty to our research and commercialization efforts with respect to those programs that are tied to such funding and may impose requirements that limit our ability to take specified actions, increase the costs of commercialization and production of product candidates developed under those programs and subject us to potential financial penalties, which could materially and adversely affect our business, financial condition, and results of operations.
−Removed: ” Although we might apply for government contracts and grants in the future, we cannot be certain that we will be successful in obtaining additional grants for any product candidates or programs.
−Removed: Risks Related to the Development of Our Product Candidates
+Added: Business disruptions could seriously harm our future revenue and financial condition and increase our costs and expenses.
+Added: Our operations, and those of our third-party research institution collaborators, contract research organizations (“CROs”), contract manufacturing operations (“CMOs”), and other contractors and consultants, could be subject to earthquakes, power
+Added: Table of Con t ents
+Added: shortages, telecommunications failures, water shortages, floods, hurricanes, typhoons, fires, extreme weather conditions, medical epidemics such as the novel coronavirus, and other natural or man-made disasters or business interruptions, for which we are partly uninsured.
+Added: In addition, we rely on our third-party research institution collaborators for conducting research and development of our product candidates, and they may be affected by government shutdowns or withdrawn funding.
+Added: The occurrence of any of these business disruptions could seriously harm our operations and financial condition and increase our costs and expenses.
+Added: Risks Related to the Discovery and Development of Our Product Candidates
Clinical trials are costly, time consuming, and inherently risky, and we may fail to demonstrate safety and efficacy to the satisfaction of applicable regulatory authorities.
4 unchanged sentences
• inability to generate satisfactory preclinical, toxicology, or other in vivo or in vitro data or diagnostics to support the initiation or continuation of clinical trials;
−Removed: delays in reaching agreement on acceptable terms with CROs and clinical trial sites, the terms of which can be subject to extensive negotiation and may vary significantly among different CROs and clinical trial sites;
+Added: • delays in reaching agreement on acceptable terms with CROs and clinical trial sites, the terms of which can be subject to extensive negotiation and may vary significantly among different CROs, clinical trial sites, and in countries or regions where our trials are conducted;
• delays in obtaining required approvals from institutional review boards or independent ethics committees at each clinical trial site;
1 unchanged sentence
• delays in recruiting eligible patients and/or subjects in our clinical trials;
−Removed: failure by clinical sites or CROs or other third parties to adhere to clinical trial requirements;
+Added: • failure by clinical sites, CROs, or other third parties to adhere to clinical trial requirements;
• failure by our clinical sites, CROs, or other third parties to perform in accordance with the good clinical practices requirements of the FDA or applicable foreign regulatory guidelines;
3 unchanged sentences
• changes in regulatory requirements and guidance that require amending or submitting new clinical protocols;
−Removed: the cost of clinical trials of our product candidates, including manufacturing costs;
+Added: • significant costs of clinical trials of our product candidates, including manufacturing activities;
• negative or inconclusive results from our clinical trials, which may result in our deciding, or regulators requiring us, to conduct additional clinical trials or abandon development programs in other ongoing or planned indications for a product candidate;
• delays in reaching agreement on acceptable terms with third-party manufacturers and the time to manufacture sufficient quantities of our product candidates acceptable for use in clinical trials.
+Added: The FDA may withdraw approval if compliance with regulatory requirements and standards is not maintained or if problems occur after the product reaches the market.
+Added: Later discovery of previously unknown problems with a product, including adverse events of unanticipated severity or frequency, or with manufacturing processes, or failure to comply with regulatory requirements, may result in revisions to the approved labeling to add new safety information;
+Added: imposition of post-market studies
+Added: Table of Con t ents
+Added: or clinical studies to assess new safety risks;
+Added: or imposition of distribution restrictions or other restrictions under a REMS program.
+Added: Other potential consequences include, among other things:
+Added: • restrictions on the marketing or manufacturing of a product, complete withdrawal of the product from the market, or product recalls;
+Added: • fines, warning letters, or holds on post-approval clinical studies;
+Added: • refusal of the FDA to approve pending applications or supplements to approved applications, or suspension or revocation of existing product approvals;
+Added: • product seizure or detention, or refusal of the FDA to permit the import or export of products;
+Added: • injunctions or the imposition of civil or criminal penalties.
+Added: The ongoing COVID-19 pandemic may materially affect our ability to complete our clinical trials in a timely fashion or at all.
Any inability to successfully complete clinical development and obtain regulatory approval for our product candidates could result in additional costs to us or impair our ability to generate revenue.
−Removed: In addition, if we make manufacturing or formulation changes to our product candidates, we may need to conduct additional non-clinical studies and the results obtained from studying such new formulation may not be consistent with previous results obtained.
+Added: In addition, if we make manufacturing or formulation changes to our product candidates, we may need to conduct additional nonclinical studies and the results obtained from studying such new formulation may not be consistent with previous results obtained.
Clinical trial delays could also shorten any periods during which our products have patent protection and may allow competitors to develop and bring products to market before we do, which could impair our ability to successfully commercialize our product candidates and may harm our business and results of operations.
−Removed: The approach we are taking to discover and develop novel therapeutics that target microRNAs is unproven and may never lead to marketable products.
−Removed: The scientific discoveries that form the basis for our efforts to discover and develop our product candidates are relatively recent.
−Removed: To date, neither we nor any other company has received regulatory approval to market therapeutics utilizing microRNA-targeted molecules.
−Removed: The scientific evidence to support the feasibility of developing drugs based on these discoveries is both preliminary and limited.
−Removed: Successful development of microRNA-targeted therapeutic products by us will require solving a number of issues, including providing suitable methods of stabilizing the therapeutic product and delivering it into target cells in the human body.
−Removed: In addition, any product candidates that we develop may not demonstrate in patients or subjects the chemical and pharmacological properties ascribed to them in laboratory and preclinical trials, and they may interact with human biological systems in unforeseen, ineffective, or even harmful ways.
−Removed: For instance, our clinical and preclinical data to date has not been fully validated and we have no way of knowing if, after validation, our clinical trial data will be complete and consistent.
−Removed: If we do not successfully develop and commercialize product candidates based upon this technological approach, we may not become profitable and the value of our capital stock may decline.
−Removed: Further, our focus on microRNA technology for developing product candidates as opposed to multiple, more proven technologies for drug development, increases the risk associated with our business.
−Removed: If we are not successful in developing an approved product using microRNA technology, we may not be able to identify and successfully implement an alternative product development strategy.
−Removed: In addition, work by other companies pursuing similar technologies may encounter setbacks and difficulties that regulators and investors may attribute to our product candidates, whether appropriately or not.
−Removed: Our microRNA-targeted therapeutic product candidates are based on a relatively novel technology, which makes it unusually difficult to predict the time and cost of development and the time and cost, or likelihood, of subsequently obtaining regulatory approval.
−Removed: To date, no microRNA-targeted therapeutics have been approved for marketing in the United States.
−Removed: We have concentrated our research and development efforts to date on a limited number of product candidates based on our microRNA-targeted therapeutic platform and identifying our initial targeted disease indications.
−Removed: Our future success depends on our successful development of viable product candidates.
−Removed: Only three of our product candidates, cobomarsen, remlarsen, and MRG-110, are in clinical development, and the remainder of our product candidates are in preclinical development.
−Removed: There can be no assurance that we will not experience problems or delays in developing our product candidates and that such problems or delays will not cause unanticipated costs, or that any such development problems can be solved.
−Removed: For instance, in December 2019, we decided to cease enrollment in our SOLAR trial, and we no longer believe the results of the SOLAR trial, due to the smaller number of patients than originally planned, would allow for accelerated approval in the United States.
−Removed: We cannot predict if we will encounter similar delays in the development of our other product candidates in the future.
−Removed: Additionally, the FDA, the European Medicines Agency, and other regulatory authorities, have relatively limited experience with microRNA-targeted therapeutics.
−Removed: No regulatory authority has granted approval to anyone, including us, to market or commercialize microRNA-targeted therapeutics, which may increase the complexity, uncertainty, and length of the regulatory review and approval process for our product candidates.
−Removed: If our product candidates fail to prove to be safe and effective, and commercially viable, our product candidate pipeline would have little, if any, value, which would have a material adverse effect on our business, financial condition, or results of operations.
−Removed: The clinical trial, product approval, and manufacturing requirements of the FDA, the European Medicines Agency, and other regulatory authorities, and the criteria these regulators use to evaluate the safety and efficacy of a product candidate, vary substantially according to the type, complexity, novelty, and intended use of the product candidate.
−Removed: The regulatory review and approval process for novel product candidates such as microRNA-targeted therapeutics can be more expensive and take longer than for other, better known or more extensively studied product candidates.
−Removed: It is difficult to determine how long it will take or how much it will cost to obtain regulatory approvals for our product candidates in either the United States or the European Union,
−Removed: or EU , or from other countries or regions of the world, or how long it will take to commercialize our product candidates, even if approved for marketing.
−Removed: Approvals by one regulatory agency may not be indicative of the likelihood of approval by other regulatory bodies.
−Removed: Delay or failure to obtain, or unexpected costs in obtaining, the regulatory approval necessary to bring a potential product candidate to market could decrease our ability to generate sufficient product revenue, and our business, financial condition, results of operations, and prospects may be harmed.
Our product candidates may cause undesirable side effects or have other properties that could delay or prevent their regulatory approval, limit the commercial viability of an approved label, or result in significant negative consequences following marketing approval, if any.
1 unchanged sentence
They additionally may result in a delay of regulatory approval by the FDA or comparable foreign authorities, or, even in the instance that an affected product candidate is approved, may result in a restrictive drug label.
−Removed: Our cobomarsen, remlarsen, and MRG-110 product candidates have been studied in only a limited number of patients with a confirmed diagnosis or healthy volunteers.
−Removed: Through the most recent clinical data release date in July 2019, the most common non-serious adverse events (occurring in ≥10% of subjects) in patients with MF, regardless of whether they were thought to be due to cobomarsen, were neutropenia, fatigue, arthralgia, injection site pain, pruritus, dry skin, nausea, diarrhea, constipation, headache, upper respiratory tract infection, nasal congestion, back pain, oropharyngeal pain, and tumor flare.
−Removed: Self-limited grade 3, 4 adverse events, probably or possibly related to cobomarsen included laboratory abnormalities (neutropenia, leukopenia, lymphopenia, hypokalemia, increase transaminases), pruritus, rash, tumor flare, tumor pain, and erythema.
−Removed: At the highest dose administered in ATLL patients, which is no longer utilized, a single episode of localized edema, exfoliative erythroderma (generalized skin scaling) in one subject, was noted as serious related adverse events.
−Removed: We may experience a higher rate or severity of adverse events and comparable or higher rates of discontinuation of trial participants in our future clinical trials.
−Removed: There is no guarantee that additional or more severe side effects will not be identified during ongoing or future clinical trials of our product candidates for current and other indications.
−Removed: Undesirable side effects and negative results for other indications may negatively impact the development and potential for approval of our product candidates for their proposed indications.
−Removed: Additionally, even if one or more of our product candidates receives marketing approval, and we or others later identify undesirable side effects caused by such products, potentially significant negative consequences could result, including but not limited to:
+Added: Even if one or more of our product candidates receives marketing approval, and we or others later identify undesirable side effects caused by such products, potentially significant negative consequences could result, including but not limited to:
• regulatory authorities may withdraw approvals of such products;
8 unchanged sentences
However, with a limited number of subjects and limited duration of exposure, we cannot be fully assured that rare and severe side effects of our product candidates will be uncovered.
−Removed: Such rare and severe side effects may only be uncovered with a significantly larger number of patients or subjects exposed to the drug.
+Added: Such rare and severe side effects may only be uncovered with a significantly larger number of patients or subjects
+Added: Table of Con t ents
+Added: exposed to the drug.
If such safety problems occur or are identified after our product candidates reach the market, the FDA may require that we amend the labeling of the product or recall the product or may even withdraw approval for the product.
−Removed: Our microRNA-targeted therapeutic approach is novel.
−Removed: Negative public opinion and increased regulatory scrutiny of microRNA or other nucleic acid-based therapies may damage public perception of the safety of our product candidates and adversely affect our ability to conduct our business or obtain regulatory approvals for our product candidates.
−Removed: MicroRNA therapy remains a novel technology, with no microRNA-targeted therapeutic product approved to date in the United States.
−Removed: Public perception may be influenced by claims that microRNA therapy is unsafe, and microRNA therapy may not gain the acceptance of the public or the medical community.
−Removed: In particular, our success will depend upon physicians who specialize in the treatment of the diseases targeted by our product candidates, prescribing therapies that involve the use of our product candidates in lieu of, or in addition to, existing therapies with which they are familiar and for which greater clinical data may be available.
−Removed: More restrictive government regulations or negative public opinion regarding microRNA or other nucleic acid-based therapeutics could have an adverse effect on our business, financial condition, or results of operations and may delay or impair the development and commercialization of our product candidates or demand for any products we may develop.
−Removed: Serious adverse events, or SAEs , in microRNA clinical trials for our competitors’ products, even if not ultimately attributable to the relevant product candidates, and the resulting publicity, could result in increased government regulation, unfavorable public perception, potential regulatory delays in the testing or approval of our product candidates, stricter labeling requirements for those product candidates that are approved, and a decrease in demand for any such product candidates.
−Removed: For instance, in June 2016, the FDA placed a regulatory hold on the clinical trial of a microRNA- or nucleic acid-focused biopharmaceutical company with a microRNA-targeted product candidate for the treatment of hepatitis C virus due to SAEs in that trial.
−Removed: This company also voluntarily halted a Phase 1 clinical trial in patients with kidney disease due to unexpected toxicity issues in July 2018.
−Removed: Another microRNA-focused biopharmaceutical company also voluntarily halted an ongoing Phase 1 clinical trial for a microRNA-targeted therapy for multiple cancers in September 2016 due to multiple immune-related serious adverse events.
−Removed: We cannot predict what effect, if any, these clinical holds will have on the government and public perception of our product candidates.
−Removed: We are heavily dependent on the success of our product candidates, which are in the early stages of clinical development.
−Removed: Some of our product candidates have produced results only in non-clinical settings, or for other indications than those for which we contemplate conducting development and seeking FDA approval, and we cannot give any assurance that we will generate data for any of our product candidates sufficiently supportive to receive regulatory approval in our planned indications, which will be required before they can be commercialized.
+Added: We are heavily dependent on the success of our product candidates, which are in the early stages of development, and we cannot give any assurance that we will generate data for any of our product candidates sufficiently supportive to receive regulatory approval in our planned indications, which will be required before they can be commercialized.
We have invested substantially all of our effort and financial resources to identify, acquire, and develop our portfolio of product candidates.
−Removed: Our future success is dependent on our ability to successfully further develop, obtain regulatory approval for, and commercialize one or more product candidates.
+Added: Our future success is dependent on our ability to successfully develop, obtain regulatory approval for, and commercialize one or more product candidates.
We currently generate no revenue from sales of any products, and we may never be able to develop or commercialize a product candidate.
−Removed: We currently have multiple product candidates in clinical development.
−Removed: Of these product candidates, cobomarsen has been predominantly administered in patients with MF.
−Removed: This is only one of the multiple indications for which we plan to develop this product candidate.
−Removed: Additionally, our clinical and preclinical data to date is not validated, and we have no way of knowing if after validation our clinical trial data will be complete and consistent.
−Removed: There can be no assurance that the data that we develop for our product candidates in our planned indications will be sufficiently supportive to obtain regulatory approval.
−Removed: In December 2019, we decided to cease enrollment in our SOLAR trial, and we no longer believe that results from the SOLAR clinical trial, based on a smaller number of patients than originally planned, could potentially allow us to apply for accelerated approval in the United States.
−Removed: As a result, we cannot guarantee if we will be able to raise sufficient capital necessary to complete a Phase 3 clinical trial of cobomarsen or when, if ever, we will be able to seek approval of cobomarsen.
−Removed: In addition, none of our other product candidates have advanced into a pivotal clinical trial for our proposed indications, and it may be years before any such clinical trial is initiated and completed, if at all.
−Removed: We are not permitted to market or promote any of our product candidates before it receives regulatory approval from the FDA or comparable foreign regulatory authorities, and we may never receive such regulatory approval for any of our product candidates.
+Added: We currently have a limited number of product candidates.
+Added: There can be no assurance that the data that we may or may not develop for our product candidates in our planned indications will be sufficiently supportive to obtain regulatory approval.
+Added: None of our product candidates have advanced through a pivotal clinical trial for our proposed indications, and it may be years before any such clinical trial is initiated and completed, if at all.
+Added: We are not permitted to market or promote any of our product candidates before they receive regulatory approval from the FDA or comparable foreign regulatory authorities, and we may never receive such regulatory approval for any of our product candidates.
We cannot be certain that any of our product candidates will be successful in clinical trials or receive regulatory approval.
4 unchanged sentences
Failure can occur at any time during the clinical trial process.
−Removed: Additionally, microRNAs are a new class of drug target and as such may have some potentially unknown risks from both an efficacy and safety perspective.
−Removed: The results of preclinical studies and early clinical
−Removed: trials of our product candidates may not be predictive of the results of larger, later-stage controlled clinical trials.
+Added: The results of preclinical studies and early clinical trials of our product candidates may not be predictive of the results of larger, later-stage controlled clinical trials.
Product candidates that have shown promising results in early-stage clinical trials may still suffer significant setbacks in subsequent clinical trials.
−Removed: Our clinical trials to date have been conducted on a small number of patients or healthy volunteers in limited numbers of clinical sites for a limited number of indications.
−Removed: We will have to conduct larger, well-controlled trials in our proposed indications to verify the results obtained to date and to support any regulatory submissions for further clinical development.
+Added: We will have to conduct well-controlled trials in our proposed indications to support any regulatory submissions for further clinical development.
A number of companies in the biopharmaceutical industry have suffered significant setbacks in advanced clinical trials due to lack of efficacy or adverse safety profiles despite promising results in earlier, smaller clinical trials.
−Removed: For instance, in June 2016, the FDA placed a regulatory hold on the clinical trial of a microRNA-focused biopharmaceutical company with a microRNA product candidate for the treatment of hepatitis C virus due to SAEs in that trial.
−Removed: This company also voluntarily halted a Phase 1 clinical trial in patients with kidney disease due to unexpected toxicity issues in July 2018.
−Removed: Another microRNA-focused biopharmaceutical company also voluntarily halted an ongoing Phase 1 clinical trial for a microRNA therapy for multiple cancers in September 2016 due to multiple immune-related severe adverse events.
Moreover, clinical data are often susceptible to varying interpretations and analyses.
−Removed: We do not know whether any Phase 2, Phase 3, or other clinical trials we are conducting or may conduct will demonstrate consistent or adequate efficacy and safety with respect to the proposed indication for use sufficient to receive regulatory approval or market our drug candidates.
+Added: We do not know whether any clinical trials we may conduct will demonstrate consistent or adequate efficacy and safety of our product candidates, with respect to the proposed indication for use, sufficient to receive regulatory approval to market our drug candidates.
We may use our financial and human resources to pursue a particular research program or product candidate and fail to capitalize on programs or product candidates that may be more profitable or for which there is a greater likelihood of success.
−Removed: Because we have limited financial and human resources, we may forego or delay pursuit of opportunities with some programs or product candidates or for other indications that later prove to have greater commercial potential.
+Added: Because we have limited financial and human resources, we may forgo or delay pursuit of opportunities with some programs or product candidates or for other indications that later prove to have greater commercial potential.
Our resource allocation decisions may cause us to fail to capitalize on viable commercial products or more profitable market opportunities.
2 unchanged sentences
If we do not accurately evaluate the commercial potential or target market for a particular product candidate, we may relinquish valuable rights to that product candidate through strategic collaborations, licensing, or other royalty arrangements in cases in which it would have been more advantageous for us to retain sole development and commercialization rights to such product candidate, or we may allocate internal resources to a product candidate in a therapeutic area in which it would have been more advantageous to enter into a collaboration arrangement.
−Removed: We may find it difficult to enroll patients or subjects in our clinical trials, in part due to the limited number of patients or subjects who have the diseases for which our product candidates are being studied.
−Removed: We cannot predict if we will continue to have difficulty enrolling patients or subjects in our current or future clinical trials.
−Removed: Difficulty in enrolling patients or subjects could delay or prevent clinical trials of our product candidates.
+Added: We may find it difficult to enroll and maintain patients or subjects in our clinical trials, in part due to the limited number of patients or subjects who have the diseases for which our product candidates are being studied.
+Added: We cannot predict if we will have difficulty enrolling and maintaining patients or subjects in our future clinical trials.
+Added: Difficulty in enrolling and maintaining patients or subjects could delay or prevent clinical trials of our product candidates.
+Added: Table of Con t ents
Identifying and qualifying patients or subjects to participate in clinical trials of our product candidates is essential to our success.
The timing of our clinical trials depends in part on the rate at which we can recruit patients or subjects to participate in clinical trials of our product candidates, and we may experience delays in our clinical trials if we encounter difficulties in enrollment.
−Removed: The eligibility criteria of our planned clinical trials may further limit the available eligible trial participants as we expect to require that patients or subjects have specific characteristics that we can measure or meet the criteria to assure their conditions are appropriate for inclusion in our clinical trials.
−Removed: For instance, prior to ending enrollment in our SOLAR trial in 2019, we planned to enroll approximately 65 patients per treatment group in the SOLAR trial of cobomarsen in patients with MF.
−Removed: Due in part to enrollment delays, we decided to end enrollment in the SOLAR trial by the end of 2019.
−Removed: We cannot guarantee that we will not encounter similar enrollment delays in future clinical trials.
−Removed: Accordingly, we may not be able to identify, recruit, and enroll a sufficient number of patients or subjects to complete our clinical trials in a timely manner because of the perceived risks and benefits of the product candidate under study, the availability and efficacy of competing therapies and clinical trials, the option for patients to choose alternate existing approved therapies, and the willingness of physicians to participate in our planned clinical trials.
−Removed: If patients or subjects are unwilling to participate in our clinical trials for any reason, the timeline for conducting trials and obtaining regulatory approval of our product candidates may be delayed.
+Added: The eligibility criteria of our clinical trials may further limit the available eligible trial participants as we expect to require that patients or subjects have specific characteristics that we can measure or meet the criteria to assure their conditions are appropriate for inclusion in our clinical trials.
+Added: Accordingly, we may not be able to identify, recruit, enroll, and maintain a sufficient number of patients or subjects to complete our future clinical trials in a timely manner because of the perceived risks and benefits of the product candidate under study, the availability and efficacy of competing therapies and clinical trials, the option for patients to choose alternate existing approved therapies, and the willingness of physicians to participate in our planned clinical trials.
+Added: Our ability to enroll patients in our planned clinical trials may be impacted by the COVID-19 pandemic, or any future disease pandemic.
+Added: Health concerns may cause patients to be unwilling to participate in clinical trials if they view themselves at particular risk from the virus, or future clinical trial sites in areas particularly impacted by the COVID-19 pandemic or any other future disease pandemic may close entirely.
+Added: We cannot guarantee that the COVID-19 pandemic, or any other future disease pandemics, will not impact enrollment in any future clinical trials.
+Added: If patients or subjects are unwilling or unable to participate in our clinical trials for any reason, the timeline for conducting trials and obtaining regulatory approval of our product candidates may be delayed.
If we experience delays in the completion of, or termination of, any clinical trials of our product candidates, the commercial prospects of our product candidates could be harmed, and our ability to generate product revenue from any of these product candidates could be delayed or prevented.
7 unchanged sentences
If we cannot successfully defend against product liability claims, we could incur substantial liability and costs.
−Removed: Some of our microRNA-targeted therapeutic candidates have shown adverse events in clinical trials, including nausea, diarrhea, fatigue, headache, upper respiratory infection, injection site erythema, neutropenia, elevated aspartate aminotransferase, creatine kinase levels, itchiness, among others.
−Removed: In almost all cases, these events were mild to moderate and self-limited.
−Removed: There is a risk that our future product candidates may induce similar or more severe adverse events.
Patients with the diseases targeted by our product candidates may already be in severe and advanced stages of disease and have both known and unknown significant preexisting and potentially life-threatening health risks.
4 unchanged sentences
As a result of these factors, a product liability claim, even if successfully defended, could have a material adverse effect on our business, financial condition, or results of operations.
−Removed: Although we have product liability insurance, which covers our clinical trials in the United States, for up to $5.0 million per occurrence, up to an aggregate limit of $5.0 million, our insurance may be insufficient to reimburse us for any expenses or losses we may suffer.
−Removed: We will also likely be required to increase our product liability insurance coverage for the advanced clinical trials that we plan to initiate.
+Added: Although we have product liability insurance, which covers our historical clinical trials in the United States, for up to $5.0 million per occurrence, up to an aggregate limit of $5.0 million, our insurance may be insufficient to reimburse us for any expenses or losses we may suffer.
+Added: We will also likely be required to increase our product liability insurance coverage for any future clinical trials that we may initiate.
If we obtain marketing approval for any of our product candidates, we will need to expand our insurance coverage to include the sale of commercial products.
3 unchanged sentences
An individual may bring a product liability claim against us alleging that one of our product candidates causes, or is claimed to have caused, an injury or is found to be unsuitable for consumer use.
−Removed: Any such product liability claims may include allegations of defects in manufacturing, defects in design, failure to warn of dangers inherent in the product, negligence, strict liability, and a breach of warranties.
+Added: Any such product
+Added: Table of Con t ents
+Added: liability claims may include allegations of defects in manufacturing, defects in design, failure to warn of dangers inherent in the product, negligence, strict liability, and a breach of warranties.
Claims could also be asserted under state consumer protection acts.
11 unchanged sentences
Product liability claims may subject us to the foregoing and other risks, which could have a material adverse effect on our business, financial condition, or results of operations.
−Removed: We may not be able to develop or identify a technology that can effectively deliver our product candidates to the intended diseased cells or tissues, and any failure in such delivery technology could adversely affect and delay the development of any or all of our other product candidates.
−Removed: In connection with our clinical trials of cobomarsen, remlarsen, and MRG-110, we have used various routes of administration, including intravenous, intralesional, subcutaneous, and intradermal injections.
−Removed: While we have observed in our clinical trials that some or all of these routes of administration may be effective in delivering adequate levels of our product candidates to produce a therapeutic response, we cannot guarantee that this will be the case in any current or future clinical trials of our product candidates.
−Removed: If we fail to develop effective routes of delivery to the target diseased cells or tissues, such failure could adversely affect and delay the development of our product candidates.
Risks Related to Regulatory Approval of Our Product Candidates and Other Legal Compliance Matters
−Removed: A potential breakthrough therapy designation by the FDA for our product candidates may not lead to a faster development or regulatory review or approval process, and it does not increase the likelihood that our product candidates will receive marketing approval.
+Added: We expect the product candidates we develop will be regulated as biologics, and therefore they may be subject to competition sooner than anticipated.
+Added: The Biologics Price Competition and Innovation Act of 2009 (“BPCIA”) was enacted as part of the Affordable Care Act to establish an abbreviated pathway for the approval of biosimilar and interchangeable biological products.
+Added: The regulatory pathway establishes legal authority for the FDA to review and approve biosimilar biologics, including the possible designation of a biosimilar as “interchangeable” based on its similarity to an approved biologic.
+Added: Under the BPCIA, an application for a biosimilar product cannot be approved by the FDA until 12 years after the reference product was approved under a Biologics License Application (“BLA”).
+Added: The law is complex and is still being interpreted and implemented by the FDA.
+Added: As a result, its ultimate impact, implementation, and meaning are subject to uncertainty.
+Added: While it is uncertain when processes intended to implement BPCIA may be fully adopted by the FDA, any of these processes could have a material adverse effect on the future commercial prospects for our biological products.
+Added: We believe that any of the product candidates we develop that is approved in the United States as a biological product under a BLA should qualify for the 12-year period of exclusivity.
+Added: However, there is a risk that this exclusivity could be shortened due to congressional action or otherwise, or that the FDA will not consider the subject product candidates to be reference products for competing products, potentially creating the opportunity for generic competition sooner than anticipated.
+Added: Moreover, the extent to which a biosimilar, once approved, will be substituted for any one of the reference products in a way that is similar to traditional generic substitution for non-biological products is not yet clear, and will depend on a number of marketplace and regulatory factors that are still developing.
+Added: In addition, the approval of a biologic product biosimilar to one of our product candidates could have a material adverse impact on our business as it may be significantly less costly to bring to market and may be priced significantly lower than our product candidates.
+Added: Table of Con t ents
+Added: We may seek Breakthrough Therapy designation for one or more of our product candidates from the FDA, but we might not receive such designation, and even if we do, such designation may not actually lead to a faster development or regulatory review or approval process.
We may seek a breakthrough therapy designation from the FDA for some of our product candidates.
16 unchanged sentences
Even if we receive accelerated approval from the FDA, the FDA may require that we conduct confirmatory trials to verify clinical benefit.
−Removed: If our confirmatory trials do not verify
−Removed: clinical benefit, or if we do not comply with rigorous post-approval requirements, the FDA may seek to withdraw accelerated approval.
−Removed: We may seek accelerated approval for our product candidates, including cobomarsen.
+Added: If our confirmatory trials do not verify clinical benefit, or if we do not comply with rigorous post-approval requirements, the FDA may seek to withdraw accelerated approval.
+Added: We may seek accelerated approval for our product candidates.
The FDA may grant accelerated approval to a product designed to treat a serious or life-threatening condition that provides meaningful therapeutic advantage over available therapies and demonstrates an effect on a surrogate endpoint or intermediate clinical endpoint that is reasonably likely to predict clinical benefit.
8 unchanged sentences
We might not be able to fulfill the FDA’s requirements in a timely manner, which would cause delays, or approval might not be granted because our submission is deemed incomplete by the FDA.
−Removed: A failure to obtain accelerated approval or any other form of expedited development, review or approval for a product candidate would result in a longer time period to commercialize such product candidate, could increase the cost of development of such product candidate, and could harm our competitive position in the marketplace.
+Added: Table of Con t ents
Even if we receive accelerated approval from the FDA, we will be subject to rigorous post-approval requirements, including submission to the FDA of all promotional materials prior to their dissemination.
4 unchanged sentences
If any of our product candidates are approved, we will be subject to ongoing regulatory requirements with respect to manufacturing, labeling, packaging, storage, advertising, promotion, sampling, record-keeping, conduct of post-marketing clinical trials, and submission of safety, efficacy, and other post-approval information, including both federal and state requirements in the United States, and requirements of comparable foreign regulatory authorities.
−Removed: Manufacturers and manufacturers’ facilities are required to continuously comply with FDA and comparable foreign requirements, including ensuring that quality control and manufacturing procedures conform to current Good Manufacturing Practices, or cGMPs, regulations, and corresponding foreign regulatory manufacturing requirements.
+Added: Manufacturers and manufacturers’ facilities are required to continuously comply with FDA and comparable foreign requirements, including ensuring that quality control and manufacturing procedures conform to cGMPs, regulations, and corresponding foreign regulatory manufacturing requirements.
As such, we and our contract manufacturers will be subject to continual review and inspections to assess compliance with cGMPs and adherence to commitments made in any new drug application or marketing authorization application.
4 unchanged sentences
An unsuccessful post-marketing clinical trial or failure to complete such a trial could result in the withdrawal of marketing approval.
−Removed: If a regulatory agency discovers previously unknown problems with a product, such as adverse events of unanticipated severity or frequency, or problems with the facility where the product is manufactured, or disagrees with the promotion, marketing or labeling of a product, the regulatory agency may impose restrictions on that product or us, including requiring withdrawal of the
−Removed: product from the market.
+Added: If a regulatory agency discovers previously unknown problems with a product, such as adverse events of unanticipated severity or frequency, or problems with the facility where the product is manufactured, or disagrees with the promotion, marketing, or labeling of a product, the regulatory agency may impose restrictions on that product or us, including requiring withdrawal of the product from the market.
If we fail to comply with applicable regulatory requirements, a regulatory agency or enforcement authority may, among other things:
8 unchanged sentences
Any failure to comply with ongoing regulatory requirements may significantly and adversely affect our ability to develop and commercialize our products, and the value of the company and our operating results would be adversely affected.
+Added: Table of Con t ents
Moreover, the FDA strictly regulates the promotional claims that may be made about drug products.
6 unchanged sentences
Healthcare legislative reform measures may have a material adverse effect on our business, financial condition, or results of operations.
−Removed: In the United States, there have been and continue to be a number of legislative initiatives to contain healthcare costs.
+Added: In the United States, there have been and continues to be a number of legislative initiatives to contain healthcare costs.
For example, in March 2010, the Affordable Care Act was passed, which was intended to substantially change the way healthcare is financed by both governmental and private insurers, and significantly impact the U.S.
1 unchanged sentence
The Affordable Care Act, among other things, addresses a new methodology by which rebates owed by manufacturers under the Medicaid Drug Rebate Program are calculated for drugs that are inhaled, infused, instilled, implanted, or injected, increases the minimum Medicaid rebates owed by manufacturers under the Medicaid Drug Rebate Program and extends the rebate program to individuals enrolled in Medicaid managed care organizations, establishes annual fees and taxes on manufacturers of specified branded prescription drugs, and promotes a new Medicare Part D coverage gap discount program.
−Removed: There remain Congressional, executive branch, judicial, and regulatory challenges to the Affordable Care Act, and both Congress and President Trump have delayed implementation or effectively repealed some of the Affordable Care Act’s requirements through legislation, Executive Orders, failures to fund, and other actions.
+Added: There remain Congressional, executive branch, judicial, and regulatory challenges to the Affordable Care Act, and both Congress and former President Trump have delayed implementation or effectively repealed some of the Affordable Care Act’s requirements through legislation, Executive Orders, failures to fund, and other actions.
For example, the Tax Act included a provision which repealed, effective January 1, 2019, the tax-based shared responsibility payment imposed by the Affordable Care Act on certain individuals who fail to maintain qualifying health coverage for all or part of a year that is commonly referred to as the “individual mandate.” Additionally, the 2020 federal spending package permanently eliminated, effective January 1, 2020, the Affordable Care Act-mandated “Cadillac” tax on high-cost employer-sponsored health coverage and medical device tax and, effective January 1, 2021, also eliminates the health insurer tax.
−Removed: Further, on December 14, 2018, a Texas U.S.
+Added: On December 14, 2018, a Texas U.S.
District Court Judge ruled that the Affordable Care Act is unconstitutional in its entirety because the “individual mandate” was repealed by Congress as part of the Tax Act.
1 unchanged sentence
Court of Appeals for the 5th Circuit upheld the District Court ruling that the individual mandate was unconstitutional and remanded the case back to the District Court to determine whether the remaining provisions of the Affordable Care Act are invalid as well.
−Removed: It is unclear how this decision, future decisions, subsequent appeals, and other efforts to repeal and replace the Affordable Care Act will impact the Affordable Care Act and our business.
+Added: On November 10, 2020 the Supreme Court heard oral arguments on the case and a decision is expected by the spring 2021.
+Added: It is unclear how such litigation and other efforts to repeal, replace or otherwise modify the Affordable Care Act will impact reimbursement of pharmaceutical products.
In addition, other legislative changes have been proposed and adopted in the United States since the Affordable Care Act was enacted, and we expect that additional state and federal healthcare reform measures will be adopted in the future, any of which could limit the amounts that federal and state governments will pay for healthcare products and services, which could result in reduced demand or lower pricing for our product candidates or additional pricing pressures.
+Added: In addition, it is possible that additional governmental action is taken to address the COVID-19 pandemic.
+Added: The CARES Act, which was signed into law in March 2020 and is designed to provide financial support and resources to individuals and businesses affected by the COVID-19 pandemic, suspended the 2% Medicare rate reduction sequester from May 1, 2020 through December 31, 2020, and extended the sequester by one year, through 2030.
+Added: In addition, it is possible that additional governmental action is taken in response to the COVID-19 pandemic.
+Added: For example, on August 6, 2020, the Trump administration issued another executive order that instructs the federal government to develop a list of “essential” medicines and then buy them and other medical supplies from U.S.
+Added: manufacturers instead of from companies around the world, including China.
+Added: The order is meant to reduce regulatory barriers to domestic pharmaceutical manufacturing and catalyze manufacturing technologies needed to keep drug prices low and the production of drug products in the United States.
We may be subject, directly or indirectly, to foreign, federal, and state healthcare fraud and abuse laws, false claims laws, and health information privacy and security laws.
If we are unable to comply, or have not fully complied, with such laws, we could face substantial penalties, sanctions, or other liability.
−Removed: Our operations may be subject to various foreign, federal, and state fraud and abuse laws, including, without limitation, the federal Anti-Kickback Statute, the federal False Claims Act, and Physician Payments Sunshine Act, the European Union’s General Data Protection Regulation, or the GDPR, and other regulations.
+Added: Table of Con t ents
+Added: Our operations may be subject to various foreign, federal, and state fraud and abuse laws, including, without limitation, the federal Anti-Kickback Statute, the federal False Claims Act, and Physician Payments Sunshine Act, the EU’s GDPR, and other regulations.
These laws may impact, among other things, our relationships with healthcare professionals and our proposed sales, marketing, and education programs.
3 unchanged sentences
• federal civil and criminal false claims laws, including the federal False Claims Act which can be enforced by individuals through civil whistleblower or qui tams actions, and civil monetary penalties laws, which prohibit, among other things, individuals or entities from knowingly presenting, or causing to be presented, claims for payment from Medicare, Medicaid, or other third-party payors that are false or fraudulent;
−Removed: the Health Insurance Portability and Accountability Act of 1996, or HIPAA, which created new federal criminal statutes that prohibit, among other things, executing a scheme to defraud any healthcare benefit program and making false statements relating to healthcare matters;
−Removed: HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act, and their implementing regulations, which imposes specified obligations, including mandatory contractual terms, with respect to safeguarding the privacy, security, and transmission of individually identifiable health information without the appropriate authorization, on entities subject to the law, such as certain healthcare providers, health plans, and healthcare clearinghouses, known as covered entities, and their respective business associates, individuals, and entities that perform services for them that involve the creation, use, maintenance, or disclosure of individually identifiable health information;
−Removed: the federal Physician Payments Sunshine Act under the Affordable Care Act which requires manufacturers of drugs, devices, biologics, and medical supplies, with certain exceptions, to report annually to the Center for Medicare and Medicaid Services, or CMS, information related to payments and other transfers of value to physicians, other healthcare providers, and teaching hospitals, and ownership and investment interests held by physicians and other healthcare providers, as well as their immediate family members and applicable group purchasing organizations;
−Removed: the GDPR and other EU member state data protection legislation as well as that of the United Kingdom, which requires data controllers and processors, to adopt administrative, physical, and technical safeguards designed to protect personal data, including health-related data, including mandatory contractual terms with third-party providers, requirements for establishing an appropriate legal basis for processing personal data, transparency requirements related to communications with data subjects regarding the processing of their personal data, standards for obtaining consent from individuals to process their personal data, notification requirements to individuals about the processing of their personal data, an individual data rights regime, mandatory data breach notifications, limitations on the retention of personal data, increased requirements pertaining to health data, and strict rules and restrictions on the transfer of personal data outside of the EU, including to the United States;
+Added: • HIPAA, which created additional federal criminal statutes that prohibit, among other things, executing a scheme to defraud any healthcare benefit program and making false statements relating to healthcare matters;
+Added: • HIPAA, as amended by HITECH, and their implementing regulations, which imposes specified obligations, including mandatory contractual terms, with respect to safeguarding the privacy, security, and transmission of individually identifiable health information without the appropriate authorization, on entities subject to the law, such as certain healthcare providers, health plans, and healthcare clearinghouses, known as covered entities, and their respective business associates, individuals, and entities that perform services for them that involve the creation, use, maintenance, or disclosure of individually identifiable health information;
+Added: • the federal Physician Payments Sunshine Act under the Affordable Care Act which requires manufacturers of drugs, devices, biologics, and medical supplies, with certain exceptions, to report annually to the CMS information related to payments and other transfers of value to physicians, as defined by such law, and teaching hospitals, and ownership and investment interests held by physicians, as well as their immediate family members and applicable group purchasing organizations.
+Added: Beginning in 2022, applicable manufacturers also will be required to report such information regarding its relationships with physician assistants, nurse practitioners, clinical nurse specialists, certified registered nurse anesthetists, and certified nurse midwives during the previous year;
+Added: • the GDPR and other EU member state data protection laws as well as those of Switzerland and the United Kingdom, which require, in part, data controllers and processors, to adopt administrative, physical, and technical safeguards designed to protect personal data, including health-related data, including mandatory contractual terms with third-party providers, requirements for establishing an appropriate legal basis for processing personal data, transparency requirements related to communications with data subjects regarding the processing of their personal data, standards for obtaining consent from individuals to process their personal data, notification requirements to individuals about the processing of their personal data, an individual data rights regime, mandatory data breach notifications, limitations on the retention of personal data, increased requirements pertaining to health data, and strict rules and restrictions on the transfer of personal data outside of the European Economic Area (the “EEA”), Switzerland, and the United Kingdom, including to the United States;
• state law equivalents of each of the above federal laws, such as anti-kickback and false claims laws that may apply to items or services reimbursed by any third-party payor, including governmental and private payors, to comply with the pharmaceutical industry’s voluntary compliance guidelines and the relevant compliance guidance promulgated by the federal government, or otherwise restrict payments that may be made to healthcare providers and other potential referral sources;
state laws that require drug manufacturers to report information related to payments and other transfers of value to physicians and other healthcare providers, marketing expenditures or drug pricing;
−Removed: state and local laws that require
−Removed: the registration of pharmaceutical sales representatives;
+Added: state and local laws that require the registration of pharmaceutical sales representatives;
and state laws governing the privacy and security of health information in specified circumstances, many of which differ from each other in significant ways and may not have the same effect, thus complicating compliance efforts.
1 unchanged sentence
In addition, recent healthcare reform legislation has strengthened these laws.
−Removed: For example, the Affordable Care Act, among other things, amends the intent requirement of the federal Anti-Kickback Statute and criminal healthcare fraud statutes, such that a person or entity no longer needs to have actual knowledge of the statute or specific intent to violate the law in order to have committed a violation.
+Added: For example, the Affordable Care Act, among other things, amends the intent requirement of the federal Anti-Kickback Statute and criminal healthcare fraud statutes, such that a person or entity
+Added: Table of Con t ents
+Added: no longer needs to have actual knowledge of the statute or specific intent to violate the law in order to have committed a violation.
Moreover, the Affordable Care Act provides that the government may assert that a claim including items or services resulting from a violation of the federal Anti-Kickback Statute constitutes a false or fraudulent claim for purposes of the federal False Claims Act.
−Removed: If our operations are found to be in violation of any of the laws described above or any other governmental regulations that apply to us, we may be subject to penalties, including significant civil, criminal, and administrative penalties, disgorgement, damages, fines, contractual damages, reputational harm, diminished profits and future earnings, exclusion from participation in government healthcare programs, such as Medicare and Medicaid, imprisonment, additional reporting requirements and/or oversight if we become subject to a corporate integrity agreement or similar agreement to resolve allegations of non-compliance with these laws, and the curtailment or restructuring of our operations, any of which could adversely affect our ability to operate our business and our results of operations.
−Removed: Reliance on government funding for our programs may add uncertainty to our research and commercialization efforts with respect to those programs that are tied to such funding and may impose requirements that limit our ability to take specified actions, increase the costs of commercialization and production of product candidates developed under those programs and subject us to potential financial penalties, which could materially and adversely affect our business, financial condition, and results of operations.
−Removed: During the course of our development of our product candidates, we have been funded in part through federal and state grants, including but not limited to the funding we received from Yale University pursuant to a subcontract agreement with Yale University.
−Removed: In addition to the funding we have received to date, we have applied and intend to continue to apply for federal and state grants to receive additional funding in the future.
−Removed: Contracts and grants funded by the U.S.
−Removed: government, state governments and their related agencies include provisions that reflect the government’s substantial rights and remedies, many of which are not typically found in commercial contracts, including powers of the government to:
−Removed: require repayment of all or a portion of the grant proceeds, in specified cases with interest, in the event we violate specified covenants pertaining to various matters that include a failure to achieve;
−Removed: specify milestones or terms relating to use of grant proceeds, or to comply with specified laws;
−Removed: terminate agreements, in whole or in part, for any reason or no reason;
−Removed: reduce or modify the government’s obligations under such agreements without the consent of the other party;
−Removed: claim rights, including intellectual property rights, in products and data developed under such agreements;
−Removed: audit contract related costs and fees, including allocated indirect costs;
−Removed: suspend the contractor or grantee from receiving new contracts pending resolution of alleged violations of procurement laws or regulations;
−Removed: manufacturing requirements for products that embody inventions conceived or first reduced to practice under such agreements;
−Removed: impose qualifications for the engagement of manufacturers, suppliers, and other contractors as well as other criteria for reimbursements;
−Removed: suspend or debar the contractor or grantee from doing future business with the government;
−Removed: control and potentially prohibit the export of products;
−Removed: pursue criminal or civil remedies under the federal False Claims Act, False Statements Act, and similar remedy provisions specific to government agreements;
−Removed: limit the government’s financial liability to amounts appropriated by the U.S.
−Removed: Congress on a fiscal year basis, thereby leaving some uncertainty about the future availability of funding for a program even after we have been funded for an initial period.
−Removed: In addition to those powers set forth above, the government funding we may receive could also impose requirements to make payments based upon sales of our products, if any, in the future.
−Removed: We may not have the right to prohibit the U.S.
−Removed: government from using specified technologies developed by it, and we may not be able to prohibit third-party companies, including our competitors, from using those technologies in providing products and services to the U.S.
−Removed: government generally takes the position that we have the right to royalty-free use of technologies that are developed under U.S.
−Removed: government contracts.
−Removed: These and other provisions of government grants may also apply to intellectual property we license now or in the future.
−Removed: In addition, government contracts and grants normally contain additional requirements that may increase our costs of doing business, reduce our profits, and expose us to liability for failure to comply with these terms and conditions.
−Removed: These requirements include, for example:
−Removed: specialized accounting systems unique to government contracts and grants;
−Removed: mandatory financial audits and potential liability for price adjustments or recoupment of government funds after such funds have been spent;
−Removed: public disclosures of some contract and grant information, which may enable competitors to gain insights into our research program;
−Removed: mandatory socioeconomic compliance requirements, including labor standards, non-discrimination and affirmative action programs, and environmental compliance requirements.
−Removed: If we fail to maintain compliance with any such requirements that may apply to us now or in the future, we may be subject to potential liability and to termination of our contracts.
+Added: If our operations are found to be in violation of any of the laws described above or any other governmental regulations that apply to us, we may be subject to penalties, including significant civil, criminal, and administrative penalties, disgorgement, damages, fines, contractual damages, reputational harm, diminished profits and future earnings, exclusion from participation in government healthcare programs, such as Medicare and Medicaid, imprisonment, additional reporting requirements and/or oversight if we become subject to a corporate integrity agreement or similar agreement to resolve allegations of noncompliance with these laws, and the curtailment or restructuring of our operations, any of which could adversely affect our ability to operate our business and our results of operations.
If we fail to comply with environmental, health, and safety laws and regulations, we could become subject to fines or penalties or incur costs that could have a material adverse effect on our business, financial condition, or results of operations.
10 unchanged sentences
Compliance or the failure to comply with such laws could increase the costs of our products and services, could limit their use or adoption, and could otherwise negatively affect our operating results and business.
−Removed: Regulation of data processing is evolving, as federal, state, and foreign governments continue to adopt new, or modify existing, laws and regulations addressing data privacy and security, and the collection, processing, storage, transfer, and use of data.
−Removed: We and our collaborators may be subject to current, new, or modified federal, state, and foreign data protection laws and regulations (e.g., laws and regulations that address data privacy and data security, including, without limitation, health data).
+Added: Regulation of personal data or personal information processing is evolving, as federal, state, and foreign governments continue to adopt new, or modify existing, laws and regulations addressing data privacy and security, and the collection, processing, storage, transfer, and use of such data.
+Added: We, our collaborators, and our service providers may be subject to current, new, or modified federal, state, and foreign data protection laws and regulations (e.g., laws and regulations that address data privacy and data security, including, without limitation, health data).
These new or proposed laws and regulations are subject to differing interpretations and may be inconsistent among jurisdictions, and guidance on implementation and compliance practices are often updated or otherwise revised, which adds to the complexity of processing personal data.
−Removed: These and other requirements could require us or our collaborators to incur additional costs to achieve compliance, limit our competitiveness, necessitate the acceptance of more onerous obligations in our contracts, restrict our ability to use, store, transfer, and process data, impact our or our collaborators’ ability to process or use data in order to support the provision of our products or services, affect our or our partners’ ability to offer our products and services or operate in certain locations, cause regulators to reject, limit, or disrupt our clinical trial activities, result in increased expenses, reduce overall demand for our products and services and make it more difficult to meet expectations of or commitments to customers or collaborators.
−Removed: In the United States, numerous federal and state laws and regulations, including state data breach notification laws, state information privacy laws (e.g., the California Consumer Privacy Act of 2018, or CCPA), state health information privacy laws, and federal and state consumer protection laws and regulations (e.g., Section 5 of the Federal Trade Commission Act), that govern the collection, use, disclosure, and protection of health-related and other personal information could apply to our operations or the operations of our collaborators.
+Added: These and other requirements could require us or our collaborators to incur additional costs to achieve compliance, limit our competitiveness, necessitate the acceptance of more onerous obligations in our contracts, restrict our ability to use, store, transfer, and process data, impact our or our collaborators’ ability to process or use data in order to support the provision of our products or services, affect our or our collaborators’ ability to offer our products and services or operate in certain locations, cause regulators to reject, limit, or disrupt our clinical trial activities, result in increased expenses, reduce overall demand for our products and services and make it more difficult to meet expectations of or commitments to customers or collaborators.
+Added: In the United States, numerous federal and state laws and regulations, including state data breach notification laws, state information privacy laws (e.g., the California Consumer Privacy Act of 2018, the “CCPA”), state health information privacy laws, and federal and state consumer protection laws and regulations (e.g., Section 5 of the Federal Trade Commission Act), that govern the collection, use, disclosure, and protection of health-related and other personal information could apply to our operations or the operations of our collaborators.
In addition, we may obtain health information from third parties (including research institutions from which we may obtain clinical trial data) that are subject to privacy and security requirements under HIPAA.
−Removed: Depending on the facts and circumstances, we could be subject to civil and criminal penalties, including if we knowingly obtain, use, or disclose individually identifiable health information maintained by a HIPAA-covered entity in a manner that is not authorized or permitted by HIPAA.
+Added: Depending on the facts and circumstances, we could be subject to civil and criminal penalties, including if we
+Added: Table of Con t ents
+Added: knowingly obtain, use, or disclose individually identifiable health information maintained by a HIPAA-covered entity in a manner that is not authorized or permitted by HIPAA.
The CCPA became effective on January 1, 2020.
−Removed: The CCPA gives California residents expanded rights to access and delete their personal information, opt out of certain personal information sharing and receive detailed information about how their personal information is used by requiring covered companies to provide new disclosures to California consumers (broadly defined as all California residents) and provide such consumers new ways to opt-out of certain sales of personal information.
−Removed: The CCPA provides for civil penalties for violations, as well as a private right of action and statutory damages for data breaches that is expected to increase class action data breach litigation.
−Removed: Although there are limited exemptions for clinical trial data, the CCPA’s implementation standards and enforcement practices are likely to remain uncertain for the foreseeable future, the CCPA may increase our compliance costs and potential liability.
+Added: The CCPA gives California residents expanded rights to access and delete their personal information, opt out of certain personal information sharing and receive detailed information about how their personal information is used by requiring covered companies to provide new disclosures to California residents and provide such residents new data privacy rights.
+Added: The CCPA imposes new operational requirements for covered businesses and provides for civil penalties for violations, as well as a private right of action and statutory damages for data breaches that are expected to increase class action data breach litigation.
+Added: Although there are limited exemptions for clinical trial data, the CCPA’s implementation standards and enforcement practices are likely to remain uncertain for the foreseeable future, and the CCPA may increase our compliance costs and potential liability.
Many similar privacy laws have been proposed at the federal level and in other states.
−Removed: Foreign data protection laws, including, without limitation, the EU’s GDPR that took effect in May 2018, and member state data protection legislation, may also apply to health-related and other personal information that we process, including, without limitation, personal data relating to clinical trial participants in the EU and the United Kingdom.
−Removed: These laws impose strict obligations on the ability to process health-related and other personal information of data subjects in the EU and the United Kingdom, including, among other things, standards relating to the privacy and security of personal data, which require the adoption of administrative, physical and technical safeguards designed to protect such information.
+Added: The CCPA exemplifies the vulnerability of our business to the evolving regulatory environment related to personal information.
+Added: Foreign data protection laws, including, without limitation, the EU’s GDPR that took effect in May 2018, and member state data protection laws, may also apply to health-related and other personal information that we process, including, without limitation, personal data relating to clinical trial participants in the EU, Switzerland, and the United Kingdom.
+Added: These laws impose strict obligations on the ability to process health-related and other personal information of data subjects in the EU, Switzerland, and the United Kingdom, including, among other things, standards relating to the privacy and security of personal data, which require the adoption of administrative, physical and technical safeguards designed to protect such information.
These laws may affect our use, collection, analysis, and transfer (including cross-border transfer) of such personal information.
These laws include several requirements relating to transparency requirements related to communications with data subjects regarding the processing of their personal data, obtaining the consent of the individuals to whom the personal data relates, limitations on data processing, establishing a legal basis for processing, notification of data processing obligations or security incidents to appropriate data protection authorities or data subjects, the security and confidentiality of the personal data and various rights that data subjects may exercise.
−Removed: The GDPR prohibits the transfer, without an appropriate legal basis, of personal data to countries outside of the European Economic Area, or EEA, such as the United States, which are not considered by the European Commission to provide an adequate level of data protection.
−Removed: Switzerland has adopted similar restrictions.
−Removed: Although there are legal mechanisms to allow for the transfer of personal data from the EEA and Switzerland to the United States, uncertainty about compliance with EU data protection laws remains and such mechanisms may not be available or applicable with respect to the personal data processing activities necessary to research, develop, and market our products and services.
−Removed: For example, ongoing legal challenges in Europe to the mechanisms allowing companies to transfer personal data from the EEA to the United States could result in further limitations on the ability to transfer personal data across borders, particularly if governments are unable or unwilling to reach new or maintain existing agreements that support cross-border data transfers, such as the EU -U.S.
+Added: The GDPR increases our obligations with respect to clinical trials conducted in the EU by expanding the definition of personal data to include coded data and requiring changes to informed consent practices and more detailed notices for clinical trial participants and investigators.
+Added: European data protection laws, including the GDPR, prohibit the transfer, without an appropriate legal basis, of personal data to countries outside of the EEA, such as the United States, which are not considered by the European Commission to provide an adequate level of data protection and as a result, increases the scrutiny for transfers of personal data from clinical trial sites located in the EU to the United States.
+Added: Switzerland and the United Kingdom have adopted similar restrictions.
+Added: Although there are legal mechanisms to allow for the transfer of personal data from the EEA, Switzerland, and United Kingdom to the United States, uncertainty about compliance with EU data protection laws remains and such mechanisms may not be available or applicable with respect to the personal data processing activities necessary to research, develop, and market our products and services.
+Added: For example, legal challenges in the EU to the mechanisms that allow companies to transfer personal data from the EU to the United States could result in further limitations on the ability to transfer personal data across borders, particularly if governments are unable or unwilling to reach new or maintain existing agreements that support cross-border data transfers, such as the EU-U.S.
and Swiss-U.S.
Privacy Shield Framework.
−Removed: Additionally, other countries have passed or are considering passing laws requiring local data residency and/or restricting the international transfer of data.
+Added: Specifically, on July 16, 2020, the Court of Justice of the EU invalidated Decision 2016/1250 on the adequacy of the protection provided by the EU-U.S.
+Added: Privacy Shield and raised questions about whether one of the primary alternatives to the EU-U.S.
+Added: Privacy Shield, namely, the European Commission’s Standard Contractual Clauses, can lawfully be used for personal data transfers from the EU to the United States or most other countries.
+Added: At present, there are few, if any, viable alternatives to the EU-U.S.
+Added: Privacy Shield and the Standard Contractual Clauses.
+Added: Similarly, the Swiss Federal Data Protection and Information Commissioner announced the use of the Swiss-U.S.
+Added: Privacy Shield is inadequate for personal data transfers from Switzerland to the U.S.
+Added: Authorities in the UK may similarly invalidate use of the EU-U.S.
+Added: Privacy Shield for transfers of personal data from the United Kingdom to the U.S.
+Added: Inability to transfer personal data from the EU, Switzerland, or United Kingdom to the United States may restrict our clinical trial activities in the EU and limit our ability to collaborate with service providers and other companies subject to European data protection laws.
+Added: Further, the United Kingdom’s decision to leave the EU, often referred to as Brexit, has created uncertainty with regard to data protection regulation in the United Kingdom.
+Added: In particular, while the Data Protection Act of 2018, which “implements” and complements the GDPR achieved Royal Assent on May 23, 2018 and is now effective in the United Kingdom, it is still unclear whether the transfer of data from the EU to the United Kingdom will in future remain lawful under GDPR.
+Added: On December 24, 2020 the EU and the United Kingdom reached agreement on the EU-UK Trade and Cooperation Agreement that with respect to data protection provides for a further transition period of up to six months as of January 1, 2021 to enable the European Commission to complete its adequacy assessment of the United Kingdom’s data protection laws.
+Added: Accordingly personal data may continue to be transferred freely between the EU and UK during that specified period.
+Added: If no adequacy decision has been adopted by the EU Commission during such period, or if the United Kingdom makes changes to its data
+Added: Table of Con t ents
+Added: protection legal framework that is in place as of January 1, 2021 without the EU’s consent, the transfer of personal data from the EU to the United Kingdom will only be permissible if EU data exporters take further steps to ensure adequacy for the protection of personal data, which may expose us to further compliance risk.
+Added: Additionally, following the United Kingdom’s withdrawal from the EU and the EEA, companies have to comply also with the United Kingdom’s data protection laws (including the GDPR as incorporated into United Kingdom national law), the latter regime having the ability to separately fine up to the greater of £17.5 million or 4% of global turnover.
Under the GDPR, regulators may impose substantial fines and penalties for non-compliance.
Companies that violate the GDPR can face fines of up to the greater of 20 million Euros or 4% of their worldwide annual turnover (revenue).
−Removed: The GDPR has increased our responsibility and liability in relation to personal data that we process, requiring us to put in place additional mechanisms to ensure compliance with the GDPR and other EU and international data protection rules.
+Added: The GDPR also permits data protection authorities to require destruction of improperly gathered or used personal data.
+Added: The GDPR and other changes in laws and regulations associated with the enhanced protection of certain types of personal data, such as health data (including personal data from our clinical trials) have increased our responsibility and liability in relation to personal data that we process, requiring us to put in place additional mechanisms to ensure compliance with such data protection laws, regulations, and rules.
+Added: Additionally, other countries have passed or are considering passing laws requiring local data residency and/or restricting the international transfer of data.
+Added: These laws, regulations, and rules could require us to change our business practices and put in place additional compliance mechanisms;
+Added: may interrupt or delay our development, regulatory, and commercialization activities;
+Added: and increase our cost of doing business.
Failure to comply with U.S.
1 unchanged sentence
Moreover, patients or subjects about whom we or our collaborators obtain information, as well as the providers who share this information with us, may contractually limit our ability to use and disclose the information.
−Removed: Claims that we have violated individuals’ privacy rights or failed to comply with data protection laws even if we are not found liable, could be expensive and time-consuming to defend and could result in adverse publicity that could harm our business.
+Added: Claims that we have violated individuals’ privacy rights or failed to comply with data protection laws or applicable privacy notices even if we are not found liable, could be expensive and time-consuming to defend and could result in adverse publicity that could harm our business.
+Added: Any failure by our third-party collaborators, service providers, contractors, or consultants to comply with applicable law, regulations, or contractual obligations related to data privacy or security could result in proceedings against us by governmental entities or others.
+Added: We may publish privacy policies and other documentation regarding our collection, processing, use, and disclosure of personal information and/or other confidential information.
+Added: Although we endeavor to comply with our published policies and other documentation, we may at times fail to do so or may be perceived to have failed to do so.
+Added: Moreover, despite our efforts, we may not be successful in achieving compliance if our employees or vendors fail to comply with our published policies and documentation.
+Added: Such failures can subject us to potential foreign, local, state, and federal action if they are found to be deceptive, unfair, or misrepresentative of our actual practices.
+Added: Moreover, subjects about whom we or our partners obtain information, as well as the providers who share this information with us, may contractually limit our ability to use and disclose the information.
+Added: Claims that we have violated individuals’ privacy rights or failed to comply with data protection laws or applicable privacy notices even if we are not found liable, could be expensive and time-consuming to defend and could result in adverse publicity that could harm our business.
Any of these matters could materially adversely affect our business, financial condition, or operational results.
+Added: Risks Related to Our Reliance on Third Parties
+Added: Our business may be adversely affected by the effects of health epidemics, including the ongoing COVID-19 pandemic, in regions where we or third parties on which we rely have business operations.
+Added: We may have future clinical trial sites in countries or regions that have been directly affected by COVID-19 and depend on third-party manufacturing operations for various stages of our supply chain that may be affected by COVID-19 in the future.
+Added: In addition, if COVID-19 continues to be a worldwide pandemic, it could materially affect our operations globally.
+Added: Our business may be adversely affected by health epidemics, including the ongoing COVID-19 pandemic, in regions where we have significant manufacturing facilities, concentrations of clinical trial sites, or other business operations.
+Added: As a result of the COVID-19 outbreak, we have implemented limitations on our operations, including a work-from-home policy, and could face further limitations in our operations in the future.
+Added: There is a risk that countries or regions may be less effective at containing COVID-19 than others, or it may be more difficult to contain if the outbreak reaches a larger population or broader geography, in which case the risks described herein could be elevated significantly.
+Added: Table of Con t ents
+Added: The ongoing COVID-19 pandemic may materially affect our ability to commence clinical trials in a timely fashion or at all.
+Added: We cannot predict if the COVID-19 pandemic, or any other future health epidemic, may cause delays to future planned clinical trials.
+Added: In addition, although we have not experienced any significant disruption in our supply chain, if COVID-19 continues to spread, third-party manufacturing of our drug product candidates and suppliers of the materials used in the production of our drug product candidates may be impacted by restrictions resulting from the COVID-19 outbreak, which may disrupt our supply chain or limit our ability to manufacture drug product candidates for our clinical trials.
+Added: The ultimate impact of the COVID-19 outbreak or a similar health epidemic is highly uncertain and subject to change.
+Added: We do not yet know the full extent of potential delays or impacts on our business, our planned clinical trials, healthcare systems, or the global economy as a whole.
+Added: However, these effects could have a material impact on our operations, and we will continue to monitor the COVID-19 situation closely.
+Added: We rely on third parties to conduct our clinical trials, manufacture our product candidates, and perform other services.
+Added: If these third parties do not successfully perform and comply with regulatory requirements, we may not be able to successfully complete clinical development, obtain regulatory approval, or commercialize our product candidates and our business could be substantially harmed.
+Added: We have relied upon and plan to continue to rely upon third-party CROs to conduct, monitor, and manage clinical programs.
+Added: We rely on these parties for execution of clinical trials, and we manage and control only some aspects of their activities.
+Added: We remain responsible for ensuring that each of our trials is conducted in accordance with the applicable protocol, legal, regulatory, and scientific standards, and our reliance on the CROs does not relieve us of our regulatory responsibilities.
+Added: We and our CROs and other vendors are required to comply with all applicable laws, regulations, and guidelines, including those required by the FDA and comparable foreign regulatory authorities for all of our product candidates in clinical development.
+Added: If we or any of our CROs or vendors fail to comply with applicable laws, regulations, and guidelines, the results generated in our clinical trials may be deemed unreliable, and the FDA or comparable foreign regulatory authorities may require us to perform additional clinical trials before approving our marketing applications.
+Added: We cannot be assured that our CROs and other vendors will meet these requirements, or that upon inspection by any regulatory authority, such regulatory authority will determine that efforts, including any of our clinical trials, comply with applicable requirements.
+Added: Our failure to comply with these laws, regulations, and guidelines may require us to repeat clinical trials, which would be costly and delay the regulatory approval process.
+Added: If any of our relationships with these third-party CROs terminate, we may not be able to enter into arrangements with alternative CROs in a timely manner or do so on commercially reasonable terms.
+Added: In addition, our CROs may not prioritize our clinical trials relative to those of other customers, and any turnover in personnel or delays in the allocation of CRO employees by the CRO may negatively affect our clinical trials.
+Added: If CROs do not successfully carry out their contractual duties or obligations or meet expected deadlines, our clinical trials may be delayed or terminated, and we may not be able to meet our current plans with respect to our product candidates.
+Added: Additionally, regional disruptions, including natural disasters or health emergencies (such as novel viruses or pandemics), could significantly disrupt the timing of clinical trials.
+Added: CROs may also involve higher costs than anticipated, which could negatively affect our financial condition and operations.
+Added: In addition, we do not currently have, nor do we currently plan to establish, the capability to manufacture product candidates for use in the conduct of our clinical trials, and we lack the resources and the capability to manufacture any of our product candidates on a clinical or commercial scale without the use of third-party manufacturers.
+Added: We plan to rely on third-party manufacturers and their responsibilities will include purchasing from third-party suppliers the materials necessary to produce our product candidates for our clinical trials and regulatory approval.
+Added: There are expected to be a limited number of suppliers for the active ingredients and other materials that we expect to use to manufacture our product candidates, and we may not be able to identify alternative suppliers to prevent a possible disruption of the manufacture of our product candidates for our clinical trials, and, if approved, ultimately for commercial sale.
+Added: Although we generally do not expect to begin a clinical trial unless we believe we have a sufficient supply of a product candidate to complete the trial, any significant delay or discontinuity in the supply of a product candidate, or the active ingredient or other material components in the manufacture of the product candidate, could delay completion of our clinical trials and potential timing for regulatory approval of our product candidates, which would harm our business and results of operations.
+Added: Our manufacturing process is complex and we may encounter difficulties in production, which would delay or prevent our ability to provide a sufficient supply of our product candidates for future clinical trials or commercialization, if approved.
+Added: The process of manufacturing our biologic product candidates is complex, highly regulated, variable, and subject to numerous risks.
+Added: Table of Con t ents
+Added: Our manufacturing process will be susceptible to product loss or failure, or product variation that may negatively impact patient outcomes, due to logistical issues associated with preparing the product for administration, infusing the patient with the product, manufacturing issues, or different product characteristics resulting from the inherent differences in starting materials, variations between reagent lots, interruptions in the manufacturing process, contamination, equipment or reagent failure, improper installation or operation of equipment and/or programs, vendor or operator error and variability in product characteristics.
+Added: Even minor variations in starting reagents and materials, or deviations from normal manufacturing processes could result in reduced production yields, product defects, manufacturing failure, and other supply disruptions.
+Added: If microbial, viral, or other contaminations are discovered in our product candidates or in any of the manufacturing facilities in which products or other materials are made, such manufacturing facilities may need to be closed for an extended period of time to investigate and remedy the contamination.
+Added: Any failure in the foregoing processes could render a batch of product unusable, could affect the regulatory approval of such product candidate, could cause us to incur fines or penalties, or could harm our reputation and that of our product candidates.
+Added: We may make changes to our manufacturing process for various reasons, such as to control costs, increase yield or dose, achieve scale, decrease processing time, increase manufacturing success rate, or for other reasons.
+Added: Changes to our process made during the course of clinical development could require us to show the comparability of the product used in earlier clinical phases or at earlier portions of a trial to the product used in later clinical phases or later portions of the trial.
+Added: Other changes to our manufacturing process made before or after commercialization could require us to show the comparability of the resulting product to the product candidate used in the clinical trials using earlier processes.
+Added: Such showings could require us to collect additional nonclinical or clinical data from any modified process prior to obtaining marketing approval for the product candidate produced with such modified process.
+Added: If such data are not ultimately comparable to that seen in the earlier trials or earlier in the same trial in terms of safety or efficacy, we may be required to make further changes to our process and/or undertake additional clinical testing, either of which could significantly delay the clinical development or commercialization of the associated product candidate, which would materially adversely affect our business, financial condition, results of operations and growth prospects.
+Added: We rely and expect to continue to rely on third parties to manufacture our clinical product supplies, and we intend to rely on third parties to produce and process our product candidates, if approved, and our commercialization of any of our product candidates could be stopped, delayed, or made less profitable if those third parties fail to obtain approval of government regulators, fail to provide us with sufficient quantities of drug product, or fail to do so at acceptable quality levels or prices.
+Added: We do not currently have, nor do we currently plan to develop, the infrastructure or capability internally to manufacture our clinical supplies for use in the conduct of our clinical trials, and we lack the resources and the capability to manufacture any of our product candidates on a clinical or commercial scale.
+Added: We currently rely on outside vendors to manufacture our clinical supplies of our product candidates and plan to continue relying on third parties to manufacture our product candidates on a commercial scale, if approved.
+Added: We do not yet have sufficient information to reliably estimate the cost of the commercial manufacturing of our product candidates and our current cost to manufacture our drug products may not be commercially feasible.
+Added: Additionally, the actual cost to manufacture our product candidates could materially and adversely affect the commercial viability of our product candidates.
+Added: As a result, we may never be able to develop a commercially viable product.
+Added: In addition, our reliance on third-party manufacturers exposes us to the following additional risks:
+Added: • We may be unable to identify manufacturers of our product candidates on acceptable terms or at all.
+Added: • Our third-party manufacturers might be unable to timely formulate and manufacture our product or produce the quantity and quality required to meet our clinical and commercial needs, if any.
+Added: • Contract manufacturers may not be able to execute our manufacturing procedures appropriately.
+Added: • Our future third-party manufacturers may not perform as agreed or may not remain in the contract manufacturing business for the time required to supply our clinical trials or to successfully produce, store, and distribute our products.
+Added: • Manufacturers are subject to ongoing periodic unannounced inspection by the FDA and some state agencies to ensure strict compliance with cGMPs and other government regulations and corresponding foreign standards.
+Added: We do not have control over third-party manufacturers’ compliance with these regulations and standards.
+Added: Table of Con t ents
+Added: • We may not own, or may have to share, the intellectual property rights to any improvements made by our third-party manufacturers in the manufacturing process for our product candidates.
+Added: • Our third-party manufacturers could breach or terminate their agreement with us.
+Added: • We may experience labor disputes or shortages, including from the effects of health emergencies (such as novel viruses or pandemics) and natural disasters.
+Added: Each of these risks could delay our clinical trials, as well as the approval, if any, of our product candidates by the FDA, or the commercialization of our product candidates, or could result in higher costs, or could deprive us of potential product revenue.
+Added: In addition, we rely on third parties to perform release testing on our product candidates prior to delivery to patients.
+Added: If these tests are not appropriately conducted and test data are not reliable, patients could be put at risk of serious harm, and this could result in product liability suits.
+Added: The manufacture of medical products is complex and requires significant expertise and capital investment, including the development of advanced manufacturing techniques and process controls.
+Added: Manufacturers of medical products often encounter difficulties in production, particularly in scaling up and validating initial production and absence of contamination.
+Added: These problems include difficulties with production costs and yields, quality control, stability of the product, quality assurance testing, operator error, shortages of qualified personnel, as well as compliance with strictly enforced federal, state, and foreign regulations.
+Added: Furthermore, if contaminants are discovered in our supply of our product candidates or in the manufacturing facilities, such manufacturing facilities may need to be closed for an extended period of time to investigate and remedy the contamination.
+Added: We cannot be assured that any stability issue or other issues relating to the manufacture of our product candidates will not occur in the future.
+Added: Additionally, our manufacturers may experience manufacturing difficulties due to resource constraints or as a result of labor disputes, shortages, including from the effects of heath emergencies (such as novel viruses or pandemics) and natural disasters, or unstable political environments.
+Added: If our manufacturers were to encounter any of these difficulties, or otherwise fail to comply with their contractual obligations, our ability to provide our product candidates to patients or subjects in clinical trials would be jeopardized.
+Added: Any delay or interruption in the supply of clinical trial supplies could delay the completion of clinical trials, increase the costs associated with maintaining clinical trial programs and, depending upon the period of delay, require us to commence new clinical trials at additional expense or terminate clinical trials completely.
+Added: We may be unable to realize the potential benefits of any collaboration.
+Added: Even if we are successful in entering into additional future collaborations with respect to the development and/or commercialization of one or more product candidates, there is no guarantee that the collaboration will be successful.
+Added: Collaborations may pose a number of risks, including:
+Added: • collaborators often have significant discretion in determining the efforts and resources that they will apply to the collaboration and may not commit sufficient resources to the development, marketing, or commercialization of the product or products that are subject to the collaboration;
+Added: • collaborators may not perform their obligations as expected;
+Added: • any such collaboration may significantly limit our share of potential future profits from the associated program and may require us to relinquish potentially valuable rights to our current product candidates, potential products, proprietary technologies, or grant licenses on terms that are not favorable to us;
+Added: • collaborators may cease to devote resources to the development or commercialization of our product candidates if the collaborators view our product candidates as competitive with their own products or product candidates;
+Added: • disagreements with collaborators, including disagreements over proprietary rights, contract interpretation, or the course of development, might cause delays or termination of the development or commercialization of product candidates, and might result in legal proceedings, which would be time consuming, distracting, and expensive;
+Added: • collaborators may be impacted by changes in their strategic focus or available funding, or business combinations involving them, which could cause them to divert resources away from the collaboration;
+Added: • collaborators may infringe the intellectual property rights of third parties, which may expose us to litigation and potential liability;
+Added: Table of Con t ents
+Added: • the collaborations may not result in us achieving revenue to justify such transactions;
+Added: • collaborations may be terminated and, if terminated, may result in a need for us to raise additional capital to pursue further development or commercialization of the applicable product candidate.
+Added: As a result, a collaboration may not result in the successful development or commercialization of our product candidates.
+Added: We enter into various contracts in the normal course of our business in which we indemnify the other party to the contract.
+Added: In the event we have to perform under these indemnification provisions, we could have a material adverse effect on our business, financial condition, and results of operations.
+Added: In the normal course of business, we periodically enter into commercial, service, licensing, consulting, and other agreements that contain indemnification provisions.
+Added: With respect to our research agreements, we typically indemnify the party and related parties from losses arising from claims relating to the products, processes, or services made, used, sold, or performed pursuant to the agreements for which we have secured licenses, and from claims arising from our or our sublicensees’ exercise of rights under the agreement.
+Added: With respect to future collaboration agreements, we may indemnify our collaborators from any third-party product liability claims that could result from the production, use, or consumption of the product, as well as for alleged infringements of any patent or other intellectual property right by a third party.
+Added: With respect to consultants, we indemnify them from claims arising from the good faith performance of their services.
+Added: Should our obligation under an indemnification provision exceed applicable insurance coverage or if we were denied insurance coverage, our business, financial condition, and results of operations could be adversely affected.
+Added: Similarly, if we are relying on a collaborator to indemnify us and the collaborator is denied insurance coverage or the indemnification obligation exceeds the applicable insurance coverage, and if the collaborator does not have other assets available to indemnify us, our business, financial condition, and results of operations could be adversely affected.
Risks Related to Our Intellectual Property
−Removed: We may not be successful in obtaining or maintaining necessary rights to microRNA targets, product compounds and processes for our development pipeline through acquisitions and in-licenses.
−Removed: Presently, we have rights to the intellectual property, through licenses from third parties and under patents and patent applications that we own, to modulate only a subset of the known microRNA targets.
−Removed: Because our programs may involve a range of microRNA targets, including targets that require the use of proprietary rights held by third parties, the growth of our business will likely depend in part on our ability to acquire, in-license, or use these proprietary rights.
−Removed: In addition, our product candidates may require specific formulations to work effectively and efficiently and these rights may be held by others.
−Removed: We may be unable to acquire or in-license any compositions, methods of use, processes, or other third-party intellectual property rights from third parties that we identify.
−Removed: The licensing and acquisition of third-party intellectual property rights is a competitive area, and a number of more established companies are also pursuing strategies to license or acquire third-party intellectual property rights that we may consider attractive.
−Removed: These established companies may have a competitive advantage over us due to their size, cash resources, and greater clinical development and commercialization capabilities.
−Removed: For example, we have previously collaborated and may continue to collaborate with U.S.
−Removed: and foreign academic institutions to accelerate our preclinical research or development under written agreements with these institutions.
−Removed: Typically, these institutions provide an option to negotiate a license to any of the institution’s rights in technology resulting from the collaboration.
−Removed: Regardless of such right of first negotiation for intellectual property, we may be unable to negotiate a license within the specified time frame or under terms that are acceptable to it.
−Removed: If we are unable to do so, the institution may offer the intellectual property rights to other parties, potentially blocking our ability to pursue our program.
−Removed: In addition, companies that perceive us to be a competitor may be unwilling to assign or license rights to us.
−Removed: We also may be unable to license or acquire third-party intellectual property rights on terms that would allow us to make an appropriate return on our investment.
−Removed: If we are unable to successfully obtain rights to third-party intellectual property rights, our business, financial condition, and prospects for growth could suffer.
−Removed: We intend to rely on patent rights for our product candidates and any future product candidates.
+Added: We intend to rely on patent rights, trade secret protections, and confidentiality agreements to protect the intellectual property related to our product candidates and any future product candidates.
If we are unable to obtain or maintain exclusivity from the combination of these approaches, we may not be able to compete effectively in our markets.
1 unchanged sentence
Our success depends in large part on our and our licensors’ ability to obtain regulatory exclusivity and maintain patent and other intellectual property protection in the United States and in other countries with respect to our proprietary technologies and product candidates.
−Removed: We have sought to protect our proprietary position by filing patent applications in the United States and abroad related to our technologies and product candidates that are important to our business.
+Added: We have sought to protect our proprietary position by filing and licensing the rights to patent applications in the United States and abroad related to our technologies and product candidates that are important to our business.
This process is expensive and time consuming, and we may not be able to file and prosecute all necessary or desirable patent applications at a reasonable cost or in a timely manner.
It is also possible that we will fail to identify patentable aspects of our research and development output before it is too late to obtain patent protection.
−Removed: The patent position of biotechnology and pharmaceutical companies generally is highly uncertain and involves complex legal and factual questions for which legal principles remain unsolved.
+Added: The patent position of biotechnology and pharmaceutical companies generally is highly uncertain and involves complex legal and factual questions for which legal principles remain unresolved.
The patent applications that we own or in-license may fail to result in issued patents with claims that cover our product candidates in the United States or in other foreign countries.
There is no assurance that all potentially relevant prior art relating to our patents and patent applications has been found, which can invalidate a patent or prevent a patent from issuing from a pending patent application.
−Removed: Even if patents do successfully issue, and even if such patents cover our product candidates, third parties may challenge their validity, enforceability, or scope, which may result in such
−Removed: patents being narrowed, found unenforceable, or invalidated.
+Added: Even if patents do successfully issue, and even if such patents cover our product candidates, third parties may challenge their validity, enforceability, or scope, which may result in such patents being narrowed, found unenforceable, or invalidated.
Furthermore, even if they are unchallenged, our patents and patent applications may not adequately protect our intellectual property, provide exclusivity for our product candidates, or prevent others from designing around our claims.
Any of these outcomes could impair our ability to prevent competition from third parties, which may have an adverse impact on our business.
−Removed: We, independently or together with our licensors, have filed several patent applications covering various aspects of our product candidates.
+Added: We, independently or together with our licensors, have filed patent applications covering various aspects of our product candidates.
We cannot offer any assurances about which, if any, patents will issue, the breadth of any such patent, or whether any issued patents will be found invalid and unenforceable or will be threatened by third parties.
−Removed: Any successful opposition to these patents or any other patents owned by or licensed to us after patent issuance could deprive us of rights necessary for the successful commercialization of any product candidates that we may develop.
+Added: Any successful opposition to these patents or any other patents owned by or licensed to us after patent issuance could deprive us of rights necessary for the
+Added: Table of Con t ents
+Added: successful commercialization of any product candidates that we may develop.
Further, if we encounter delays in regulatory approvals, the period of time during which we could market a product candidate under patent protection could be reduced.
3 unchanged sentences
In the United States, the statutory expiration of a patent is generally 20 years after it is filed.
−Removed: Additional patent terms may be available through a patent term adjustment process, resulting from the United States Patent and Trademark Office, or USPTO, delays during prosecution.
+Added: Additional patent terms may be available through a patent term adjustment process, resulting from the United States Patent and Trademark Office (“USPTO”) delays during prosecution.
Although various extensions may be available, the life of a patent, and the protection it affords, is limited.
8 unchanged sentences
Obtaining and enforcing patents in the biotechnology industry involve both technological and legal complexity, and is therefore costly, time-consuming, and inherently uncertain.
−Removed: In addition, the United States has recently enacted and is currently implementing wide-ranging patent reform legislation.
−Removed: Supreme Court rulings have narrowed the scope of patent protection available in specified circumstances and weakened the rights of patent owners in specified situations.
+Added: In addition, the United States in 2011 enacted and is still currently implementing wide-ranging patent reform legislation.
+Added: Recent rulings from the U.S.
+Added: Supreme Court and the Court of Appeals for the Federal Circuit have narrowed the scope of patent protection available in specified circumstances and weakened the rights of patent owners in specified situations.
In addition to increasing uncertainty with regard to our ability to obtain patents in the future, this combination of events has created uncertainty with respect to the value of patents, once obtained.
4 unchanged sentences
and Association for Molecular Pathology v.
−Removed: Myriad Genetics, Inc., and applied the Myriad ruling to natural products and principles including all naturally occurring nucleic acids.
+Added: Myriad Genetics, Inc., and applied the Myriad ruling to natural products and principles including all naturally occurring molecules.
In addition, the USPTO continues to provide updates to its guidance and this is a developing area.
The USPTO guidance may make it impossible for us to pursue similar patent claims in patent applications we may prosecute in the future.
−Removed: Our patent portfolio contains claims of various types and scope, including chemically modified mimics, inhibitors, as well as methods of medical treatment.
+Added: Our patent portfolio contains claims of various types and scope and methods of medical treatment.
The presence of varying claims in our patent portfolio significantly reduces, but may not eliminate, our exposure to potential validity challenges.
patent applications containing a claim not entitled to priority before March 16, 2013, there is a greater level of uncertainty in the patent law.
−Removed: On September 16, 2011, the Leahy-Smith America Invents Act, or the Leahy-Smith Act, was signed into law.
+Added: On September 16, 2011, the Leahy-Smith America Invents Act (the “Leahy-Smith Act”) was signed into law.
The Leahy-Smith Act includes a number of significant changes to U.S.
−Removed: These include provisions that affect
−Removed: the way patent applications will be prosecuted and may also affect patent litigation.
+Added: These include provisions that affect the way patent applications will be prosecuted and may also affect patent litigation.
The USPTO has promulgated regulations and developed procedures to govern administration of the Leahy-Smith Act, and many of the substantive changes to patent law associated with the Leahy-Smith Act, and in particular, the first to file provisions, did not come into effect until March 16, 2013.
1 unchanged sentence
However, the Leahy-Smith Act and its implementation could increase the uncertainties and costs surrounding the prosecution of our patent applications and the enforcement or defense of our issued patents, all of which could have a material adverse effect on our business, financial condition, or results of operations.
+Added: Table of Con t ents
An important change introduced by the Leahy-Smith Act is that, as of March 16, 2013, the United States transitioned to a “first-to-file” system for deciding which party should be granted a patent when two or more patent applications are filed by different parties claiming the same invention.
4 unchanged sentences
Among some of the other changes introduced by the Leahy-Smith Act are changes that limit where a patentee may file a patent infringement suit and new procedures providing opportunities for third parties to challenge any issued patent in the USPTO.
−Removed: Included in these new procedures is a process known as Inter Partes Review, or IPR, which has been generally used by many third parties over the past four years to invalidate patents.
−Removed: The IPR process is not limited to patents filed after the Leahy-Smith Act was enacted and would therefore be available to a third party seeking to invalidate any of our U.S.
+Added: Included in these new procedures is a process known as Inter Partes Review (“IPR”), which has been generally used by many third parties since the enactment of the Leahy-Smith Act to invalidate patents.
+Added: The IPR process is not limited to patents filed after the Leahy-Smith Act was enacted and would, therefore, be available to a third party seeking to invalidate any of our Licensor’s U.S.
patents, even those filed before March 16, 2013.
16 unchanged sentences
Numerous third-party U.S.
−Removed: issued patents and pending applications exist in the area of microRNA.
−Removed: We are aware of U.S.
−Removed: and foreign patents and pending patent applications owned by third parties that cover therapeutic uses of microRNA replacements and inhibitors.
+Added: issued patents and pending applications exist in the area of our product candidates.
From time to time, we may also monitor these patents and patent applications.
1 unchanged sentence
and foreign patent offices to challenge the validity of these patents and patent applications.
−Removed: In addition, or alternatively, we may consider
−Removed: whether to seek to negotiate a license of rights to technology covered by one or more of such patents and patent applications.
−Removed: If any patents or patent applications cover our product candidates or technologies, we may not be free to manufacture or market our product candidates, including cobomarsen, remlarsen, or MRG-110, as planned, absent such a license, which may not be available to us on commercially reasonable terms, or at all.
+Added: In addition, or alternatively, we may consider whether to seek to negotiate a license of rights to technology covered by one or more of such patents and patent applications.
+Added: If any patents or patent applications cover our product candidates or technologies, we may not be free to manufacture or market our product candidates as planned, absent such a license, which may not be available to us on commercially reasonable terms, or at all.
+Added: Table of Con t ents
It is also possible that we have failed to identify relevant third-party patents or applications.
21 unchanged sentences
Even if we are able to license or acquire third-party intellectual property rights that are necessary for our product candidates, there can be no assurance that they will be available on favorable terms.
−Removed: We collaborate with U.S.
−Removed: and foreign academic institutions to identify product candidates, accelerate our research, and conduct development.
−Removed: Typically, these institutions have provided us with an option to negotiate an exclusive license to any of the institution’s rights in the patents or other intellectual property resulting from the collaboration.
−Removed: Regardless of such option, we may be unable to negotiate a license within the specified timeframe or under terms that are acceptable to us.
−Removed: If we are unable to do so, the institution may offer the intellectual property rights to other parties, potentially blocking our ability to pursue a program of interest to us.
If we are unable to successfully obtain and maintain rights to required third-party intellectual property, we may have to abandon development of that product candidate or pay additional amounts to the third party, and our business and financial condition could suffer.
−Removed: The patent protection and patent prosecution for some of our product candidates is dependent on third parties.
+Added: The patent protection and patent prosecution for some of our product candidates are dependent on third parties.
While we normally seek and gain the right to fully prosecute the patents relating to our product candidates, there may be times when patents relating to our product candidates are controlled by our licensors.
−Removed: For instance, under our agreement with RICC, we have negotiated the right to direct RICC’s representatives with regard to specific patent matters, but these representatives still are responsible for the prosecution of patents and patent applications licensed to us under the agreement.
−Removed: If RICC or any of our future licensors fail to appropriately follow our instructions with regard to the prosecution and maintenance of patent protection for patents covering any of our product candidates, our ability to develop and commercialize those product candidates may be adversely affected, and we may not be able to prevent competitors from making, using, importing, and selling competing products.
−Removed: In addition, even where we now have the right to control patent prosecution of patents and patent applications we have licensed from third parties, we may still be adversely affected or prejudiced by actions or inactions of our licensors in effect from actions prior to us assuming control over patent prosecution.
+Added: If any of our licensors fail to appropriately follow our instructions with regard to the prosecution and maintenance of patent protection for patents covering any of our product candidates, our ability to develop and commercialize those product candidates may be adversely affected, and we may not be able to prevent competitors from making, using, importing, and selling competing products.
+Added: In addition, even where we
+Added: Table of Con t ents
+Added: now have the right to control patent prosecution of patents and patent applications we have licensed from third parties, we may still be adversely affected or prejudiced by actions or inactions of our licensors in effect from actions prior to us assuming control over patent prosecution.
If we fail to comply with obligations in the agreements under which we license intellectual property and other rights from third parties or otherwise experience disruptions to our business relationships with our licensors, we could lose license rights that are important to our business.
−Removed: We are a party to a number of intellectual property license and supply agreements that are important to our business and expect to enter into additional license agreements in the future.
+Added: We are a party to intellectual property licenses and supply agreements that are important to our business and expect to enter into additional license agreements in the future.
Our existing agreements impose, and we expect that future license agreements will impose, various diligence, milestone payments, royalties, purchasing, and other obligations on us.
5 unchanged sentences
Grounds for a validity challenge could be an alleged failure to meet any of several statutory requirements, including lack of novelty, obviousness, written description, clarity, or non-enablement.
−Removed: Grounds for an unenforceability assertion could be an allegation that someone connected with prosecution of the patent withheld relevant information from the USPTO, or made a misleading statement, during prosecution.
+Added: Grounds for an unenforceability assertion could be an allegation that someone connected with prosecution of the patent withheld material information from the USPTO, or made a misleading statement, during prosecution.
The outcome following legal assertions of invalidity and unenforceability is unpredictable.
14 unchanged sentences
We may not be able to protect our intellectual property rights throughout the world.
−Removed: Filing, prosecuting, and defending patents on product candidates in all countries throughout the world would be prohibitively expensive, and our intellectual property rights in some countries outside the United States can be less extensive than those in the United States.
+Added: Filing, prosecuting, and defending patents on product candidates in all countries throughout the world would be prohibitively expensive, and our intellectual property rights in some countries outside the United States can be less extensive than those in
+Added: Table of Con t ents
+Added: the United States.
In addition, the laws of some foreign countries do not protect intellectual property rights to the same extent as federal and state laws in the United States.
6 unchanged sentences
Accordingly, our efforts to enforce our intellectual property rights around the world may be inadequate to obtain a significant commercial advantage from the intellectual property that we develop or license.
−Removed: Risks Related to Our Reliance on Third Parties
−Removed: We rely on third parties to conduct our clinical trials, manufacture our product candidates, and perform other services.
−Removed: If these third parties do not successfully perform and comply with regulatory requirements, we may not be able to successfully complete clinical development, obtain regulatory approval, or commercialize our product candidates and our business could be substantially harmed.
−Removed: We have relied upon and plan to continue to rely upon third-party CROs to conduct, monitor, and manage our ongoing clinical programs.
−Removed: We rely on these parties for execution of clinical trials, and we manage and control only some aspects of their activities.
−Removed: We remain responsible for ensuring that each of our trials is conducted in accordance with the applicable protocol, legal, regulatory, and scientific standards, and our reliance on the CROs does not relieve us of our regulatory responsibilities.
−Removed: We and our CROs and other vendors are required to comply with all applicable laws, regulations, and guidelines, including those required by the FDA and comparable foreign regulatory authorities for all of our product candidates in clinical development.
−Removed: If we or any of our CROs or vendors fail to comply with applicable laws, regulations, and guidelines, the results generated in our clinical trials may be deemed unreliable, and the FDA or comparable foreign regulatory authorities may require us to perform additional clinical trials before approving our marketing applications.
−Removed: We cannot be assured that our CROs and other vendors will meet these requirements, or that upon inspection by any regulatory authority, such regulatory authority will determine that efforts, including any of our clinical trials, comply with applicable requirements.
−Removed: Our failure to comply with these laws, regulations, and guidelines may require us to repeat clinical trials, which would be costly and delay the regulatory approval process.
−Removed: If any of our relationships with these third-party CROs terminate, we may not be able to enter into arrangements with alternative CROs in a timely manner or do so on commercially reasonable terms.
−Removed: In addition, our CROs may not prioritize our clinical trials relative to those of other customers, and any turnover in personnel or delays in the allocation of CRO employees by the CRO may negatively affect our clinical trials.
−Removed: If CROs do not successfully carry out their contractual duties or obligations or meet expected deadlines, our clinical trials may be delayed or terminated, and we may not be able to meet our current plans with respect to our
−Removed: product candidates.
−Removed: Additionally, regional disruptions, including natural disasters or health emergencies (such as novel viruses or pandemics), could significantly disrupt the timing of clinical trials.
−Removed: CROs may also involve higher costs than anticipated, which could negatively affect our financial condition and operations.
−Removed: In addition, we do not currently have, nor do we currently plan to establish, the capability to manufacture product candidates for use in the conduct of our clinical trials, and we lack the resources and the capability to manufacture any of our product candidates on a clinical or commercial scale without the use of third-party manufacturers.
−Removed: We plan to rely on third-party manufacturers and their responsibilities will include purchasing from third-party suppliers the materials necessary to produce our product candidates for our clinical trials and regulatory approval.
−Removed: There are expected to be a limited number of suppliers for the active ingredients and other materials that we expect to use to manufacture our product candidates, and we may not be able to identify alternative suppliers to prevent a possible disruption of the manufacture of our product candidates for our clinical trials, and, if approved, ultimately for commercial sale.
−Removed: Although we generally do not expect to begin a clinical trial unless we believe we have a sufficient supply of a product candidate to complete the trial, any significant delay or discontinuity in the supply of a product candidate, or the active ingredient or other material components in the manufacture of the product candidate, could delay completion of our clinical trials and potential timing for regulatory approval of our product candidates, which would harm our business and results of operations.
−Removed: We rely and expect to continue to rely on third parties to manufacture our clinical product supplies, and we intend to rely on third parties to produce and process our product candidates, if approved, and our commercialization of any of our product candidates could be stopped, delayed, or made less profitable if those third parties fail to obtain approval of government regulators, fail to provide us with sufficient quantities of drug product, or fail to do so at acceptable quality levels or prices.
−Removed: We do not currently have, nor do we currently plan to develop, the infrastructure or capability internally to manufacture our clinical supplies for use in the conduct of our clinical trials, and we lack the resources and the capability to manufacture any of our product candidates on a clinical or commercial scale.
−Removed: We currently rely on outside vendors to manufacture our clinical supplies of our product candidates and plan to continue relying on third parties to manufacture our product candidates on a commercial scale, if approved.
−Removed: We do not yet have sufficient information to reliably estimate the cost of the commercial manufacturing of our product candidates and our current cost to manufacture our drug products may not be commercially feasible.
−Removed: Additionally, the actual cost to manufacture our product candidates could materially and adversely affect the commercial viability of our product candidates.
−Removed: As a result, we may never be able to develop a commercially viable product.
−Removed: In addition, our reliance on third-party manufacturers exposes us to the following additional risks:
−Removed: We may be unable to identify manufacturers on acceptable terms or at all.
−Removed: Our third-party manufacturers might be unable to timely formulate and manufacture our product or produce the quantity and quality required to meet our clinical and commercial needs, if any.
−Removed: Contract manufacturers may not be able to execute our manufacturing procedures appropriately.
−Removed: Our future third-party manufacturers may not perform as agreed or may not remain in the contract manufacturing business for the time required to supply our clinical trials or to successfully produce, store, and distribute our products.
−Removed: Manufacturers are subject to ongoing periodic unannounced inspection by the FDA and some state agencies to ensure strict compliance with cGMPs and other government regulations and corresponding foreign standards.
−Removed: We do not have control over third-party manufacturers’ compliance with these regulations and standards.
−Removed: We may not own, or may have to share, the intellectual property rights to any improvements made by our third-party manufacturers in the manufacturing process for our product candidates.
−Removed: Our third-party manufacturers could breach or terminate their agreement with us.
−Removed: Labor disputes or shortages, including from the effects of health emergencies (such as novel viruses or pandemics) and natural disasters.
−Removed: Each of these risks could delay our clinical trials, as well as the approval, if any, of our product candidates by the FDA, or the commercialization of our product candidates, or could result in higher costs, or could deprive us of potential product revenue.
−Removed: addition, we rely on third parties to perform release testing on our product candidates prior to delivery to patients.
−Removed: If these tests are not appropriately conducted and test data are not reliable, patients could be put at risk of serious harm and could result in product liability suits.
−Removed: The manufacture of medical products is complex and requires significant expertise and capital investment, including the development of advanced manufacturing techniques and process controls.
−Removed: Manufacturers of medical products often encounter difficulties in production, particularly in scaling up and validating initial production and absence of contamination.
−Removed: These problems include difficulties with production costs and yields, quality control, including stability of the product, quality assurance testing, operator error, shortages of qualified personnel, as well as compliance with strictly enforced federal, state, and foreign regulations.
−Removed: Furthermore, if contaminants are discovered in our supply of our product candidates or in the manufacturing facilities, such manufacturing facilities may need to be closed for an extended period of time to investigate and remedy the contamination.
−Removed: We cannot be assured that any stability or other issues relating to the manufacture of our product candidates will not occur in the future.
−Removed: Additionally, our manufacturers may experience manufacturing difficulties due to resource constraints or as a result of labor disputes, shortages, including from the effects of heath emergencies (such as novel viruses or pandemics) and natural disasters,
−Removed: or unstable political environments.
−Removed: If our manufacturers were to encounter any of these difficulties, or otherwise fail to comply with their contractual obligations, our ability to provide our product candidates to patients or subjects in clinical trials would be jeopardized.
−Removed: Any delay or interruption in the supply of clinical trial supplies could delay the completion of clinical trials, increase the costs associated with maintaining clinical trial programs and, depending upon the period of delay, require us to commence new clinical trials at additional expense or terminate clinical trials completely.
−Removed: Our business could be adversely affected by the effects of health epidemics, including the recent COVID-19 outbreak, in regions where we or third parties on which we rely have clinical trial sites or other business operations.
−Removed: We have a clinical trial sites in countries that have been directly affected by COVID-19 and depend on third party manufacturing operations for various stages of our supply chain.
−Removed: In addition, if COVID-19 becomes a worldwide pandemic, it could materially affect our operations globally.
−Removed: Our business could be adversely affected by health epidemics in regions where we have significant manufacturing facilities, concentrations of clinical trial sites or other business operations.
−Removed: If the recent COVID-19 outbreak continues to spread, we may need to limit operations or implement limitations, including work-from-home policies.
−Removed: There is a risk that other countries or regions may be less effective at containing COVID-19, or it may be more difficult to contain if the outbreak reaches a larger population or broader geography, in which case the risks described herein could be elevated significantly.
−Removed: In particular, third party manufacturing of our drug product candidates and suppliers of the materials used in the production of our drug product candidates may be impacted by restrictions resulting from the coronavirus outbreak which may disrupt our supply chain or limit our ability to manufacture drug product candidates for our clinical trials.
−Removed: In addition, our clinical trials may be affected by the COVID-19 outbreak.
−Removed: Site initiation, patient enrollment, distribution of drug product candidates, study monitoring, and data cleaning may be delayed due to changes in hospital policies, local regulations, and/or prioritization of hospital resources toward the COVID-19 outbreak.
−Removed: If COVID-19 continues to spread, some patients and clinical investigators may not be able to comply with clinical trial protocols.
−Removed: For example, quarantines may impede patient movement, affect sponsor access to study sites, or interrupt healthcare services, and we may be unable to obtain samples necessary for testing.
−Removed: The ultimate impact of the COVID-19 outbreak or a similar health epidemic is highly uncertain and subject to change.
−Removed: We do not yet know the full extent of potential delays or impacts on our business, our clinical trials, healthcare systems or the global economy as a whole.
−Removed: However, these effects could have a material impact on our operations, and we will continue to monitor the COVID-19 situation closely.
−Removed: We may be unable to realize the potential benefits of any collaboration.
−Removed: Even if we are successful in entering into a collaboration with respect to the development and/or commercialization of one or more product candidates, there is no guarantee that the collaboration will be successful.
−Removed: Collaborations may pose a number of risks, including:
−Removed: collaborators often have significant discretion in determining the efforts and resources that they will apply to the collaboration and may not commit sufficient resources to the development, marketing, or commercialization of the product or products that are subject to the collaboration;
−Removed: collaborators may not perform their obligations as expected;
−Removed: any such collaboration may significantly limit our share of potential future profits from the associated program and may require us to relinquish potentially valuable rights to our current product candidates, potential products, proprietary technologies, or grant licenses on terms that are not favorable to us;
−Removed: collaborators may cease to devote resources to the development or commercialization of our product candidates if the collaborators view our product candidates as competitive with their own products or product candidates;
−Removed: disagreements with collaborators, including disagreements over proprietary rights, contract interpretation, or the course of development, might cause delays or termination of the development or commercialization of product candidates, and might result in legal proceedings, which would be time consuming, distracting, and expensive;
−Removed: collaborators may be impacted by changes in their strategic focus or available funding, or business combinations involving them, which could cause them to divert resources away from the collaboration;
−Removed: collaborators may infringe the intellectual property rights of third parties, which may expose us to litigation and potential liability;
−Removed: the collaborations may not result in us achieving revenue to justify such transactions;
−Removed: collaborations may be terminated and, if terminated, may result in a need for us to raise additional capital to pursue further development or commercialization of the applicable product candidate.
−Removed: As a result, a collaboration may not result in the successful development or commercialization of our product candidates.
−Removed: For instance, in October 2011, we entered into the Servier Collaboration Agreement with Servier for the research, development, and commercialization of RNA-targeting therapeutics in cardiovascular disease, which was subsequently amended.
−Removed: In August 2019, Servier terminated the Servier Collaboration Agreement effective in February 2020.
−Removed: As a result, no product candidate will ever be successfully commercialized under the Servier Collaboration Agreement.
−Removed: While we regained all global rights to MRG-110 in all indications as a result of the termination of the Servier Collaboration Agreement, we cannot guarantee that we will be able to continue development of MRG-110 without finding a new collaborator in the future.
−Removed: Any future collaboration regarding MRG-110 may be on substantially worse commercial terms than those offered by Servier or we may not be successful in entering into any future collaborations regarding MRG-110.
−Removed: As a result, we cannot guarantee when, if ever, we will be able to further develop MRG-110 following termination of the Servier Collaboration Agreement.
−Removed: We enter into various contracts in the normal course of our business in which we indemnify the other party to the contract.
−Removed: In the event we have to perform under these indemnification provisions, we could have a material adverse effect on our business, financial condition, and results of operations.
−Removed: In the normal course of business, we periodically enter into academic, commercial, service, collaboration, licensing, consulting, and other agreements that contain indemnification provisions.
−Removed: With respect to our academic and other research agreements, we typically indemnify the institution and related parties from losses arising from claims relating to the products, processes, or services made, used, sold, or performed pursuant to the agreements for which we have secured licenses, and from claims arising from our or our sublicensees’ exercise of rights under the agreement.
−Removed: With respect to our collaboration agreements, we indemnify our collaborators from any third-party product liability claims that could result from the production, use, or consumption of the product, as well as for alleged infringements of any patent or other intellectual property right by a third party.
−Removed: With respect to consultants, we indemnify them from claims arising from the good faith performance of their services.
−Removed: Should our obligation under an indemnification provision exceed applicable insurance coverage or if we were denied insurance coverage, our business, financial condition, and results of operations could be adversely affected.
−Removed: Similarly, if we are relying on a collaborator to indemnify us and the collaborator is denied insurance coverage or the indemnification obligation exceeds the applicable insurance coverage, and if the collaborator does not have other assets available to indemnify us, our business, financial condition, and results of operations could be adversely affected.
Risks Related to Commercialization of Our Product Candidates
−Removed: We currently have limited marketing and sales experience.
If we are unable to establish sales and marketing capabilities or enter into agreements with third parties to market and sell our product candidates, we may be unable to generate any revenue.
11 unchanged sentences
Even if we are able to successfully enter into a collaboration regarding the development or commercialization of our product candidates, we cannot guarantee that such a collaboration will be successful.
−Removed: For instance, in October 2011, we entered into the Servier Collaboration Agreement with Servier for the research, development, and commercialization of RNA-targeting therapeutics in cardiovascular disease, which was subsequently amended.
−Removed: In August 2019, Servier terminated the Servier Collaboration Agreement effective in February 2020.
−Removed: As a result, no product candidate will ever be successfully commercialized under the Servier Collaboration Agreement.
−Removed: While we regained all global rights to MRG-110 in all indications as a result of the termination of the Servier Collaboration Agreement, we cannot guarantee that we will be able to continue development of MRG-110 without finding a new collaborator in the future.
−Removed: Any future collaboration regarding MRG-110 may be on substantially worse commercial terms than those offered by Servier or we may not be successful in entering into any future collaborations regarding MRG-110.
−Removed: As a result, we cannot guarantee when, if ever, we will be able to further develop MRG-110 following termination of the Servier Collaboration Agreement.
−Removed: Any delays in identifying suitable collaborators and entering into agreements to develop and/or commercialize our product candidates could delay the development or commercialization of our product candidates, which may reduce their competitiveness even if they reach the market.
+Added: Any delays in identifying suitable collaborators and entering into agreements to develop and/or commercialize our product candidates could delay the development or commercialization of our product candidates, which may reduce their
+Added: Table of Con t ents
+Added: competitiveness even if they reach the market.
Absent a strategic collaborator, we would need to undertake development and/or commercialization activities at our own expense.
1 unchanged sentence
If we are unable to do so, we may not be able to develop our product candidates or bring them to market and our business may be materially and adversely affected.
−Removed: If the market opportunities for our product candidates are smaller than we believe they are, we may not meet our revenue expectations and, assuming approval of a product candidate, our business may suffer.
−Removed: Because the patient populations in the market for our product candidates may be small, we must be able to successfully identify patients and acquire a significant market share to achieve profitability and growth.
−Removed: Given the small number of patients who have the diseases that we are targeting, our eligible patient population and pricing estimates may differ significantly from the actual market addressable by our product candidates.
−Removed: For instance, the lead indication of cobomarsen is MF.
−Removed: The estimated prevalence of MF is 16,000 to 20,000 cases in the United States, only a subset of which may benefit from treatment with cobomarsen.
−Removed: Our projections of both the number of people who have this disease, as well as the subset of people with this disease who have the potential to benefit from treatment with our product candidates, are based on our beliefs and estimates.
−Removed: These estimates have been derived from a variety of sources, including the scientific literature, patient foundations, or market research, and may prove to be incorrect.
−Removed: Further, new studies may change the estimated incidence or prevalence of these diseases.
−Removed: The number of patients may turn out to be lower than expected.
−Removed: Additionally, while we believe that the data in our Phase 1 clinical trials for cobomarsen, remlarsen, and MRG-110 are supportive of application to other indications, there can be no assurance that our clinical trials in those indications will support efficacy of our product candidates in such expanded indications.
−Removed: Likewise, the potentially addressable patient population for each of our product candidates may be limited or may not be amenable to treatment with our product candidates, and new patients may become increasingly difficult to identify or gain access to, which would adversely affect our business, financial condition, results of operations and prospects.
We face substantial competition and our competitors may discover, develop, or commercialize products faster or more successfully than us.
The development and commercialization of new drug products is highly competitive.
−Removed: We face competition from major pharmaceutical companies, specialty pharmaceutical companies, biotechnology companies, universities, and other research institutions worldwide with respect to cobomarsen, remlarsen, MRG-110, and the other product candidates that we may seek to develop or commercialize in the future.
−Removed: We are aware that the following companies have therapeutics marketed or in development for CTCL:
−Removed: Argenx, Bristol-Myers Squibb Company, Celgene Corporation, Helsinn Group, innate Pharma, Kyowa Hakko Kirin, Merck & Co., Inc., Mylan Pharmaceuticals Inc., Novartis International AG, Spectrum Pharmaceuticals, Inc., Seattle Genetics, Inc., Takeda Pharmaceutical Company Ltd, and Valeant Pharmaceuticals International, Inc.
−Removed: We are also aware that several companies have marketed therapeutics for pulmonary fibrosis, including Boehringer Ingelheim GmbH and F.
−Removed: Hoffmann-La Roche Ltd.
−Removed: Our competitors may succeed in developing, acquiring, or licensing technologies and drug products that are more effective or less costly than cobomarsen, remlarsen, MRG-110, or any other product candidates that we are currently developing or that we may develop, which could render our product candidates obsolete and noncompetitive.
−Removed: In addition to the competition we face from alternative therapies for the diseases we intend to target with our product candidates, we are aware of several companies that are also working specifically to develop microRNA-targeted therapeutics, including Regulus Therapeutics, Inc., and InteRNA Technologies, B.V.
−Removed: Further, there are several companies working to develop other types of oligonucleotide therapeutic products, including Ionis Pharmaceuticals, Inc., Alnylam Pharmaceuticals, Inc., Arrowhead Pharmaceuticals, Inc., Dicerna Pharmaceuticals, Inc., STELLAS Life Sciences Group, Inc., Silence Therapeutics AG, and Translate Bio, Inc.
+Added: We face competition from major pharmaceutical companies, specialty pharmaceutical companies, biotechnology companies, universities, and other research institutions worldwide with respect to our product candidates that we may seek to develop or commercialize in the future.
+Added: We are aware that the following companies have therapeutics marketed or in development for TED:
+Added: Horizon Therapeutics and Immunovant, Inc.
+Added: If approved, VRDN-001 will also compete against generic medications, such as corticosteroids, that are prescribed for and surgical procedures for the treatment of TED.
+Added: Our competitors may succeed in developing, acquiring, or licensing technologies and drug products that are more effective or less costly than our product candidates that we are currently developing or that we may develop, which could render our product candidates obsolete and noncompetitive.
+Added: Our competitors may also adopt a similar licensing and development strategy as ours with regard to the development of an existing anti-IGF-1R monoclonal antibody for the treatment of TED.
+Added: If any competitor was able to effect this strategy in a more efficient manner, there may be less demand for our product candidates if any are approved.
Many of our competitors have substantially greater financial, technical, and other resources, such as larger research and development staff and experienced marketing and manufacturing organizations.
Third-party payors, including governmental and private insurers, may also encourage the use of generic products.
−Removed: For example, if cobomarsen, remlarsen, or MRG-110 is approved, it may be priced at a significant premium over other competitive products.
−Removed: This may make it difficult for cobomarsen, remlarsen, MRG-110, or any other future products to compete with these products.
+Added: For example, if VRDN-001 is approved, it may be priced at a significant premium over other competitive products.
+Added: This may make it difficult for VRDN-001 or any other future products to compete with these products.
If our competitors obtain marketing approval from the FDA or comparable foreign regulatory authorities for their product candidates more rapidly than us, it could result in our competitors establishing a strong market position before we are able to enter the market.
4 unchanged sentences
These organizations may also establish exclusive collaborative or licensing relationships with our competitors.
−Removed: Failure of cobomarsen, remlarsen, MRG-110, or other product candidates to effectively compete against established treatment options or in the future with new products currently in development would harm our business, financial condition, results of operations, and prospects.
+Added: Failure of VRDN-001 or our other product candidates to effectively compete against established treatment options or in the future with new products currently in development would harm our business, financial condition, results of operations, and prospects.
The commercial success of any of our current or future product candidates will depend upon the degree of market acceptance by physicians, patients, third-party payors, and others in the medical community.
Even with the approvals from the FDA and comparable foreign regulatory authorities, the commercial success of our products will depend in part on the healthcare providers, patients, and third-party payors accepting our product candidates as medically useful, cost-effective, and safe.
−Removed: Any product that we bring to the market may not gain market acceptance by physicians, patients,
−Removed: and third-party payors.
+Added: Any product that we bring to the market may not gain market acceptance by physicians, patients, and third-party payors.
The degree of market acceptance of any of our products will depend on a number of factors, including but not limited to:
2 unchanged sentences
• the clinical indications for which approval is granted, including any limitations or warnings contained in a product’s approved labeling;
+Added: Table of Con t ents
• the convenience and ease of administration;
9 unchanged sentences
We may not be successful in any efforts to identify, license, discover, develop, or commercialize additional product candidates.
−Removed: Although a substantial amount of our effort will focus on the continued clinical testing, potential approval, and commercialization of our existing product candidates, the success of our business is also expected to depend in part upon our ability to identify, license, discover, develop, or commercialize additional product candidates.
+Added: Although a substantial amount of our effort will focus on clinical testing, potential approval, and commercialization of our existing product candidates, the success of our business is also expected to depend in part upon our ability to identify, license, discover, develop, or commercialize additional product candidates.
Research programs to identify new product candidates require substantial technical, financial, and human resources.
11 unchanged sentences
If any of these events occur, we may be forced to abandon our development efforts for a program or programs, or we may not be able to identify, license, discover, develop, or commercialize additional product candidates, which would have a material adverse effect on our business, financial condition, or results of operations and could potentially cause us to cease operations.
+Added: Table of Con t ents
Failure to obtain or maintain adequate reimbursement or insurance coverage for our products, if any, could limit our ability to market those products and decrease our ability to generate revenue.
3 unchanged sentences
In addition, there is significant uncertainty related to the insurance coverage and reimbursement for newly approved products.
−Removed: In the United States, the principal decisions about coverage and reimbursement for new drugs are typically made by CMS, which is an agency within the U.S.
−Removed: Department of Health and Human Services that decides whether and to what extent a new drug will be covered and reimbursed under Medicare.
+Added: In the United States, the principal decisions about coverage and reimbursement for new drugs are typically made by CMS, which is an agency within HHS that decides whether and to what extent a new drug will be covered and reimbursed under Medicare.
Private third-party payors tend to follow the coverage and reimbursement policies established by CMS to a substantial degree, but also have their own methods and approval process apart from Medicare determinations.
8 unchanged sentences
Congressional inquiries and proposed and enacted federal and state legislation designed to, among other things, bring more transparency to drug pricing, review the relationship between pricing and manufacturer patient programs, reduce the cost of drugs under Medicare, and reform government program reimbursement methodologies for drugs.
−Removed: At the federal level, the Trump administration’s budget proposal for fiscal year 2021 includes a $135 billion allowance to support legislative proposals seeking to reduce drug prices, increase competition, lower out-of-pocket drug costs for patients, and increase patient access to lower-cost generic and biosimilar drugs.
−Removed: In addition, the Trump administration released a “Blueprint” to lower drug prices and reduce out of pocket costs of drugs that contains additional proposals to increase manufacturer competition, increase the negotiating power of certain federal healthcare programs, incentivize manufacturers to lower the list price of their products, and reduce the out of pocket costs of drug products paid by consumers.
−Removed: The Department of Health and Human Services has started soliciting feedback on some of these measures and, at the same time, is implementing others under its existing authority.
+Added: At the federal level, the Trump administration’s budget proposal for fiscal year 2021 included a $135 billion allowance to support legislative proposals seeking to reduce drug prices, increase competition, lower out-of-pocket drug costs for patients, and increase patient access to lower-cost generic and biosimilar drugs.
+Added: On March 10, 2020, the Trump administration sent “principles” for drug pricing to Congress, calling for legislation that would, among other things, cap Medicare Part D beneficiary out-of-pocket pharmacy expenses, provide an option to cap Medicare Part D beneficiary monthly out-of-pocket expenses, and place limits on pharmaceutical price increases.
+Added: In addition, the Trump administration previously released a “Blueprint” to lower drug prices and reduce out of pocket costs of drugs that contained proposals to increase manufacturer competition, increase the negotiating power of certain federal healthcare programs, incentivize manufacturers to lower the list price of their products, and reduce the out of pocket costs of drug products paid by consumers.
+Added: HHS solicited feedback on some of these measures and has implemented others under its existing authority.
+Added: Additionally, on July 24, 2020, President Trump announced four executive orders related to prescription drug pricing that attempt to implement several of the Trump administration proposals, including (i) a policy that would tie certain Medicare Part B drug prices to international drug prices, or the “most favored nation price,” the details of which were released on September 13, 2020 and also expanded to cover certain Part D drugs;
+Added: (ii) an order that directs HHS to finalize the Canadian drug importation proposed rule previously issued by HHS and makes other changes allowing for personal importation of drugs from Canada;
+Added: (iii) an order that directs HHS to finalize the rulemaking process on modifying the Anti-Kickback Statute safe harbors for discounts for plans, pharmacies, and pharmaceutical benefit managers;
+Added: (iv) a policy that reduces costs of insulin and epipens to patients of federally qualified health centers.
+Added: Although the Biden administration has stayed the effective dates of some last-minute drug price regulations issued by the Trump administration, Congress and the Biden administration have each indicated that they will continue to seek new legislative and/or administrative measures to control drug costs.
At the state level, legislatures have increasingly passed legislation and implemented regulations designed to control pharmaceutical and biological product pricing, including price or patient reimbursement constraints, discounts, restrictions on certain product access and marketing cost disclosure and transparency measures, and, in some cases, designed to encourage importation from other countries and bulk purchasing.
+Added: Table of Con t ents
We expect to experience pricing pressures in connection with products due to the increasing trend toward managed healthcare, including the increasing influence of health maintenance organizations and additional legislative changes.
2 unchanged sentences
Risks Related to Our Business Operations
−Removed: Our future success depends in part on our ability to retain our president and chief executive officer and to attract, retain, and motivate other qualified personnel.
−Removed: We are highly dependent on William S.
−Removed: Marshall, Ph.D., our president and chief executive officer, the loss of whose services may adversely impact the achievement of our objectives.
−Removed: Marshall could leave our employment at any time, as he is an “at will” employee.
+Added: Our future success depends in part on our ability to retain our chief executive officer and to attract, retain, and motivate other qualified personnel.
+Added: We are highly dependent on Jonathan Violin, our president and chief executive officer, the loss of whose services may adversely impact the achievement of our objectives.
+Added: Violin could leave our employment at any time, as he is classified as an “at-will” employee.
Recruiting and retaining other qualified employees, consultants, and advisors for our business, including scientific and technical personnel, will also be critical to our success.
There is currently a shortage of highly qualified personnel in our industry, which is likely to continue.
−Removed: Additionally, this shortage of highly qualified personnel is particularly acute in the area where we are located.
As a result, competition for personnel is intense, and the turnover rate can be high.
2 unchanged sentences
The inability to recruit and retain qualified personnel, or the loss of the services of Dr.
−Removed: Marshall, may impede the progress of our research, development, and commercialization objectives and would negatively impact our ability to succeed in our product development strategy.
+Added: Violin, may impede the progress of our research, development, and commercialization objectives and would negatively impact our ability to succeed in our product development strategy.
We will need to expand our organization and we may experience difficulties in managing this growth, which could disrupt our operations.
5 unchanged sentences
Our future financial performance and our ability to commercialize product candidates and compete effectively will depend, in part, on our ability to effectively manage any future growth.
−Removed: If we do not effectively manage changes in our operations, our business may be harmed;
−Removed: we have taken substantial restructuring charges in the past and we may need to take material restructuring charges in the future.
−Removed: The expansion of our business, as well as business contractions and other changes in our business requirements, have in the past, and may in the future, require that we adjust our business and cost structures by incurring restructuring charges.
−Removed: Restructuring activities involve reductions in our workforce at some locations and closure of certain facilities.
−Removed: All of these changes have in the past placed, and may in the future place, considerable strain on our research and development activities and financial and management control systems and resources, including decision support, accounting management, information systems and facilities.
−Removed: If we do not effectively manage our financial and management controls, reporting systems, and procedures to manage our employees, our business could be harmed.
−Removed: For instance, in 2019 we began implementing two phases of a cost restructuring plan to streamline the organization, reduce costs, and direct resources to advance cobomarsen and miR-29 mimics, including remlarsen and MRG-229, while reducing investments in new discovery research.
−Removed: The restructuring plan identified approximately 44 positions for elimination, or approximately 50% of our total workforce, primarily associated with research and development and corresponding project, general, and administrative support.
−Removed: Through December 31, 2019, we had recorded approximately $2.0 million in restructuring expense and expect to incur another $0.2 million during the first half of 2020.
−Removed: We may be required to incur additional charges in the future to align our operations and cost structures with global economic conditions, market demands, cost competitiveness, and our clinical development activities.
−Removed: If we are required to incur additional restructuring charges in the future, our operating results, financial condition, and cash flows could be adversely impacted.
−Removed: Additionally, there are other potential risks associated with our restructuring that could adversely affect us, such as delays encountered with the finalization and implementation of the restructuring activities, work stoppages, and the failure to achieve targeted cost savings.
Failure in our information technology and storage systems or those of third parties upon whom we rely could significantly disrupt the operation of our business and adversely impact our financial condition.
−Removed: Our ability to execute our business plan and maintain operations depends on the continued and uninterrupted performance of our information technology, or IT, systems or those of third parties upon whom we rely.
+Added: Our ability to execute our business plan and maintain operations depends on the continued and uninterrupted performance of our information technology (“IT”) systems or those of third parties upon whom we rely.
IT systems are vulnerable to risks and damages from a variety of sources, including telecommunications or network failures, malicious human acts, and natural disasters (such as a tornado, an earthquake, or a fire).
8 unchanged sentences
If such an event were to affect our supply chain, it could have a material adverse effect on our business.
+Added: Table of Con t ents
A network or data security incident may allow unauthorized access to our network or data, which could result in a material disruption of our clinical trials, harm our reputation, harm our business, create additional liability and adversely impact our financial results or operational results.
Increasingly, we are subject to a wide variety of threats on our information networks, and systems and those of our service providers or collaborators.
−Removed: In addition to threats from natural disasters, telecommunications and electrical failures, traditional computer hackers, malicious code (such as malware, viruses, worms and ransomware), employee error, theft or misuse, password spraying, phishing and distributed denial‑of‑service, or DDOS, attacks, we now also face threats from sophisticated nation‑state and nation‑state supported actors who engage in attacks (including advanced persistent threat intrusions) that add to the risks to our internal networks, our third‑party service providers, our collaborators and the information that they store and process.
+Added: In addition to threats from natural disasters, telecommunications and electrical failures, traditional computer hackers, malicious code (such as malware, viruses, worms, and ransomware), employee error, theft or misuse, password spraying, phishing, and distributed denial-of-service (“DDOS”) attacks, we now also face threats from sophisticated nation-state and nation-state supported actors who engage in attacks (including advanced persistent threat intrusions) that add to the risks to our internal networks, our third-party service providers, our collaborators and the information that they store and process.
Despite significant efforts to create security barriers to safeguard against such threats, it is virtually impossible for us to entirely mitigate these risks.
8 unchanged sentences
In addition, we cannot be sure that any existing insurance coverage and coverage for errors and omissions will continue to be available on acceptable terms or that our insurers will not deny coverage as to any future claim.
−Removed: Any failure or perceived failure by us or any collaborators, service providers or others to comply with our privacy, confidentiality, data security or similar obligations to third parties, or any data security incidents or other security breaches that result in the unauthorized access, acquisition or disclosure of sensitive information (including, without limitation personally identifiable information), may result in governmental investigations, enforcement actions, regulatory fines, litigation, or public statements
−Removed: against us, could cause third parties to lose trust in us or result in claims against us.
+Added: Any failure or perceived failure by us or any collaborators, service providers, or others to comply with our privacy, confidentiality, data security or similar obligations to third parties, or any data security incidents or other security breaches that result in the unauthorized access, acquisition, or disclosure of sensitive information (including, without limitation personally identifiable information), may result in governmental investigations, enforcement actions, regulatory fines, litigation, or public statements against us, could cause third parties to lose trust in us or result in claims against us.
Any of these events could cause harm to our reputation, business, financial condition, or operational results.
Our ability to use net operating loss carryforwards and certain other tax attributes to offset future taxable income or taxes may be limited.
−Removed: Our net operating loss, or NOL, carryforwards could expire unused and be unavailable to offset future income tax liabilities because of their limited duration or because of restrictions under U.S.
+Added: Our net operating loss (“NOL”) carryforwards could expire unused and be unavailable to offset future income tax liabilities because of their limited duration or because of restrictions under U.S.
Our NOLs generated in tax years ending on or prior to December 31, 2017 are only permitted to be carried forward for 20 years under applicable U.S.
1 unchanged sentence
It is uncertain if and to what extent various states will conform to the Tax Act.
−Removed: In addition, under Sections 382 and 383 of the Internal Revenue Code of 1986, as amended, or the Code, and corresponding provisions of state law, if a corporation undergoes an “ownership change,” which is generally defined as a greater than 50% change, by value, in its equity ownership over a three-year period, the corporation’s ability to use its pre-change NOL carryforwards and other pre-change tax attributes to offset its post-change income or taxes may be limited.
−Removed: Our most recent analysis of possible ownership changes was completed for certain tax periods ending through February 13, 2017, the date of a merger between us, then named Signal Genetics, Inc., and a private corporation, then called Miragen Therapeutics, Inc., or Private miRagen, in which our wholly owned subsidiary was merged with and into Private miRagen.
−Removed: Immediately following this transaction, we completed a short-form merger with Private miRagen in which we were the surviving corporation and changed our name to Miragen Therapeutics, Inc.
−Removed: These transactions are referred to herein as the Merger.
−Removed: The Merger resulted in an ownership change for us and, accordingly, our NOL and tax credit carryforwards are subject to limitation.
−Removed: It is possible that we have in the past undergone and may in the future undergo, additional ownership changes besides the Merger, that could result in additional limitations on our NOL and tax credit carryforwards.
+Added: In addition, under Sections 382 and 383 of the Internal Revenue Code of 1986, as amended (the “Code”), and corresponding provisions of state law, if a corporation undergoes an “ownership change,” which is generally defined as a greater than 50% change, by value, in its equity ownership over a three-year period, the corporation’s ability to use its pre-change NOL carryforwards and other pre-change tax attributes to offset its post-change income or taxes may be limited.
+Added: Our most recent analysis of possible ownership changes was completed for certain tax periods ending through December 31 2020.
+Added: It is possible that we have in the past undergone and may in the future undergo, additional ownership changes that could result in additional limitations on our NOL and tax credit carryforwards.
In addition, at the state level, there may be periods during which the use of net operating losses is suspended or otherwise limited, which could accelerate or permanently increase state taxes owed.
+Added: Table of Con t ents
Consequently, even if we achieve profitability, we may not be able to utilize a material portion of our NOL carryforwards and certain other tax attributes, which could have a material adverse effect on cash flow and results of operations.
15 unchanged sentences
Risks Related to Ownership of our Common Stock
−Removed: The market price of our common stock has historically been volatile, and the market price of our common stock may drop in the future.
−Removed: The market price of our common stock has been, and may continue to be, subject to significant fluctuations.
−Removed: Market prices for securities of early-stage pharmaceutical, biotechnology, and other life sciences companies have historically been particularly volatile.
−Removed: Some of the factors that may cause the market price of our common stock to fluctuate include:
−Removed: our ability to obtain regulatory approvals for cobomarsen, remlarsen, MRG-110, or other product candidates, and delays or failures to obtain such approvals;
−Removed: failure of any of our product candidates, if approved, to achieve commercial success;
−Removed: failure to maintain our existing third-party license and supply agreements;
−Removed: changes in laws or regulations applicable to our product candidates;
−Removed: any inability to obtain adequate supply of our product candidates or the inability to do so at acceptable prices;
−Removed: adverse regulatory authority decisions;
−Removed: introduction of new products, services, or technologies by our competitors;
−Removed: failure to meet or exceed financial and development projections we may provide to the public and the investment community;
−Removed: the perception of the pharmaceutical industry by the public, legislatures, regulators, and the investment community;
−Removed: announcements of significant acquisitions, strategic collaborations, joint ventures, or capital commitments by us or our competitors;
−Removed: disputes or other developments relating to proprietary rights, including patents, litigation matters, and our ability to obtain patent protection for our technologies;
−Removed: additions or departures of key personnel;
−Removed: significant lawsuits, including patent or stockholder litigation;
−Removed: if securities or industry analysts do not publish research or reports about our business, or if they issue an adverse or misleading opinion regarding our business and stock;
−Removed: changes in the market valuations of similar companies;
−Removed: general market or macroeconomic conditions;
−Removed: sales of our common stock by us or our stockholders in the future;
−Removed: trading volume of our common stock;
−Removed: announcements by commercial partners or competitors of new commercial products, clinical progress or the lack thereof, significant contracts, commercial relationships, or capital commitments;
−Removed: adverse publicity relating to microRNA-targeted therapeutics generally, including with respect to other products and potential products in such markets;
−Removed: the introduction of technological innovations or new therapies that compete with our potential products;
−Removed: changes in the structure of health care payment systems;
−Removed: period-to-period fluctuations in our financial results.
−Removed: Moreover, the capital markets in general have experienced substantial volatility that has often been unrelated to the operating performance of individual companies.
−Removed: These broad market fluctuations may also adversely affect the trading price of our common stock.
−Removed: In the past, following periods of volatility in the market price of a company’s securities, stockholders have often instituted class action securities litigation against those companies.
−Removed: Such litigation, if instituted, could result in substantial costs and diversion of management attention and resources, which could significantly harm our profitability and reputation.
−Removed: Our failure to meet the continued listing requirements of The Nasdaq Capital Market could result in a delisting of our common stock.
−Removed: Our common stock is currently listed on The Nasdaq Capital Market.
−Removed: To maintain the listing of our common stock on The Nasdaq Capital Market, we are required to meet certain listing requirements, including, among others, a minimum bid price of $1.00 per share.
−Removed: If we fail to satisfy the continued listing requirements of The Nasdaq Capital Market, such as the corporate governance requirements or the minimum closing bid price requirement, The Nasdaq Capital Market may take steps to delist our common stock, which could have a materially adverse effect on our ability to raise additional funds as well as the price and liquidity of our common stock.
−Removed: Such a delisting would likely have a negative effect on the price of our common stock and would impair our stockholders’ ability to sell or purchase our common stock when they wish to do so.
−Removed: In the event of a delisting, we can provide no assurance that any action taken by us to restore compliance with listing requirements would allow our common stock to become listed again, stabilize the market price or improve the liquidity of our common stock, prevent our common stock from dropping below the Nasdaq minimum bid price requirement, or prevent future non-compliance with The Nasdaq Capital Market’s listing requirements.
−Removed: On October 28, 2019, we received a letter from the Listing Qualifications Department of The Nasdaq Stock Market LLC, or Nasdaq, notifying us that the listing of our common stock was not in compliance with Nasdaq Listing Rule 5550(a)(2) for continued listing on The Nasdaq Capital Market, as the minimum bid price of our listed securities was less than $1.00 per share for the previous 30 consecutive business days.
−Removed: Under Nasdaq Listing Rule 5810(c)(3)(A), we have a period of 180 calendar days, or until April 27, 2020, to regain compliance with the rule.
−Removed: To regain compliance, during this 180-day compliance period, the minimum bid price of our listed securities must close at $1.00 per share or more for a minimum of 10 consecutive business days.
−Removed: In the event that we do not regain compliance with the Nasdaq Listing Rules prior to the expiration of the 180-day compliance period, we may be eligible for additional time to regain compliance pursuant to Nasdaq Listing Rule 5810(c)(3)(A)(ii) by meeting the continued listing requirement for market value of publicly held shares and all other applicable standards for initial listing on The Nasdaq Capital Market, with the exception of the minimum bid price requirement.
−Removed: In addition, we would need to provide written notice to Nasdaq of our intention to cure the minimum bid price deficiency during the second compliance period by effecting a reverse stock split, if necessary.
−Removed: As part of its review process, the Nasdaq staff will make a determination of whether it believes we will be able to cure this deficiency.
−Removed: Should the Nasdaq staff conclude that we will not be able to cure the deficiency, or should we determine not to make the required representation, Nasdaq will provide notice that our shares of common stock will be subject to delisting.
−Removed: If we do not regain compliance within the allotted compliance period(s), including any extensions that may be granted by Nasdaq, Nasdaq will provide notice that our shares of common stock will be subject to delisting.
−Removed: At such time, we may appeal the delisting determination to a hearings panel pursuant to the procedures set forth in the applicable Nasdaq Listing Rules.
−Removed: We intend to actively monitor the minimum bid price of our listed securities and, as appropriate, will consider available options to resolve the deficiencies and regain compliance with the Nasdaq Listing Rules, including effecting a reverse stock split.
−Removed: There can be no assurance that we will be successful in maintaining the listing of our common stock on The Nasdaq Capital Market.
−Removed: This could impair the liquidity and market price of our common stock.
−Removed: In addition, the delisting of our common stock from a national exchange could have a material adverse effect on our access to capital markets, and any limitation on market liquidity or reduction in the price of our common stock as a result of that delisting could adversely affect our ability to raise capital on terms acceptable to us, or at all.
−Removed: We incur costs and demands upon management as a result of complying with the laws and regulations affecting public companies.
−Removed: We incur significant legal, accounting, and other expenses associated with public-company reporting requirements.
−Removed: We also incur costs associated with corporate governance requirements, including requirements under the Sarbanes-Oxley Act, as well as rules implemented by the SEC and The Nasdaq Stock Market LLC, or Nasdaq.
−Removed: These rules and regulations increase our legal and
−Removed: financial compliance costs and make some activities more time-consuming and costly.
−Removed: These rules and regulations may also make it difficult and expensive for us to obtain directors’ and officers’ liability insurance.
−Removed: As a result, it may be more difficult for us to attract and retain qualified individuals to serve on our board of directors or as our executive officers, which may adversely affect investor confidence and could cause our business or stock price to suffer.
−Removed: From June 2014 to December 31, 2019, we qualified as an “emerging growth company” as defined in the Jumpstart Our Business Startups Act of 2012, or the JOBS Act.
−Removed: As of January 1, 2020, we no longer qualified as emerging growth company.
−Removed: While we were an “emerging growth company,” we were allowed certain exemptions from various reporting requirements that are applicable to public companies that are not “emerging growth companies” including, but not limited to, not being required to comply with the auditor attestation requirements of Section 404 of the Sarbanes-Oxley Act of 2002, or the Sarbanes-Oxley Act, reduced disclosure obligations regarding executive compensation and financial statements in our periodic reports and proxy statements, and exemptions from the requirements of holding a nonbinding advisory vote to approve executive compensation and shareholder approval of any golden parachute payments not previously approved.
−Removed: Because we are no longer an emerging growth company, we will incur significant additional costs associated with compliance with reporting requirements applicable to non-emerging growth companies.
Anti-takeover provisions in our charter documents and under Delaware law and the terms of some of our contracts could make an acquisition of us more difficult and may prevent attempts by our stockholders to replace or remove our management.
5 unchanged sentences
In addition, the provisions of our warrants issued in connection with the 2020 Public Offering may delay or prevent a change in control of our company.
−Removed: For example, under such warrants, each warrantholder has the right to demand that we redeem the warrant for a cash amount equal to the Black-Scholes value of a portion of the warrant upon the occurrence of specified events, including a merger, an asset sale or any other change of control transaction.
+Added: Pursuant to such warrants, under certain circumstances each warrant holder has the right to demand that we redeem the warrant for a cash amount equal to the Black-Scholes value of a portion of the warrant upon the occurrence of specified events, including a merger, an asset sale or certain other change of control transactions.
A takeover of us may trigger the requirement that we redeem the warrants, which could make it more costly for a potential acquirer to engage in a business combination transaction with us.
1 unchanged sentence
Our Bylaws provide that the Court of Chancery of the State of Delaware is the sole and exclusive forum for any derivative action or proceeding brought on our behalf, any action asserting a breach of fiduciary duty owed by any of our directors, officers, or other employees to us or our stockholders, any action asserting a claim against us arising pursuant to any provisions of the Delaware General Corporation Law, our certificate of incorporation or our bylaws, or any action asserting a claim against us that is governed by the internal affairs doctrine.
−Removed: While these choice of forum provisions do not apply to suits brought to enforce a duty or liability created by the Securities Act, the Exchange Act, or any other claim for which the federal courts have exclusive jurisdiction, the choice of forum provision may limit a stockholder’s ability to bring a claim in a judicial forum that it finds favorable for disputes with us or our directors, officers, or other employees, which may discourage such lawsuits against our and our directors, officers, and other employees.
+Added: While these choice of forum provisions do not apply to suits brought to
+Added: Table of Con t ents
+Added: enforce a duty or liability created by the Securities Act of 1933, as amended (the “Securities Act”), the Exchange Act, or any other claim for which the federal courts have exclusive jurisdiction, the choice of forum provision may limit a stockholder’s ability to bring a claim in a judicial forum that it finds favorable for disputes with us or our directors, officers, or other employees, which may discourage such lawsuits against our and our directors, officers, and other employees.
If a court were to find the choice of forum provision contained in the bylaws to be inapplicable or unenforceable in an action, we may incur additional costs associated with resolving such action in other jurisdictions.
7 unchanged sentences
Future sales of shares by existing stockholders could cause our stock price to decline.
+Added: Concurrently and in connection with the acquisition of Private Viridian, certain Private Viridian securityholders as of immediately prior to the acquisition, and our directors and officers as of immediately following the acquisition entered into the Lock-up Agreements, pursuant to which each such stockholder will be subject to a 180-day lockup on the sale or transfer of shares of our common stock held by each such stockholder at the closing of the acquisition, including those shares received by Private Viridian securityholders in the acquisition.
+Added: Upon expiration of this 180-day lockup period, these shares will become eligible for sale in the public market.
If our stockholders sell, or indicate an intention to sell, substantial amounts of our common stock in the public market after legal restrictions on resale lapse, the trading price of our common stock could decline.
−Removed: In addition, shares of our common stock that are subject to our outstanding options will become eligible for sale in the public market to the extent permitted by the provisions of various vesting agreements and Rules 144 and 701 under the Securities Act of 1933, as amended.
+Added: In addition, shares of our common stock that are subject to our outstanding options will become eligible for sale in the public market to the extent permitted by the provisions of various vesting agreements and Rules 144 and 701 under the Securities Act.
Future sales and issuances of equity and debt could result in additional dilution to our stockholders.
2 unchanged sentences
As a result, our stockholders may experience additional dilution, which could cause our stock price to fall.
−Removed: For instance, in March 2017, we entered into the ATM Agreement with Cowen, under which we may offer and sell, from time to time, at our sole discretion, shares of our common stock having an aggregate offering price of up to $50.0 million through Cowen as our sales agent.
−Removed: Through March 13, 2019 , we had sold, pursuant to the terms of the ATM Agreement, approximately 1,871,386 shares of our common stock for aggregate net proceeds of approximately $11.0 million after deducting initial expenses for executing the “at the market offering” and commissions to Cowen as sales agent.
−Removed: In February 2018, we entered into the 2018 Underwriting Agreement with Jefferies LLC, Evercore Group L.L.C., and Deutsche Bank Securities Inc., as representatives of the several underwriters.
−Removed: Pursuant to the 2018 Underwriting Agreement, in February 2018 we sold 7,414,996 shares of our common stock, which resulted in net proceeds of approximately $37.9 million after deducting underwriting commissions and discounts and other offering expenses payable by us.
−Removed: In August 2018 , we entered into the LLS Stock Purchase Agreement with LLS, which was later assigned to LLS TAP, for the sale of up to $5.0 million of shares of our common stock to LLS and its affiliates under the LLS Purchase Agreement.
−Removed: Through March 13, 2020, we had issued an aggregate of 757,351 shares of our common stock to LLS and its affiliates in the LLS Offering, for aggregate net proceeds of approximately $1.4 million , after deducting expenses incurred in connection with the LLS Offering.
−Removed: As a result of the modifications of the SOLAR trial we announced in December 2019, we do not anticipate meeting the milestones under the LLS Stock Purchase Agreement and as such, do not expect we will receive the remaining proceeds available under the LLS Stock Purchase Agreement unless the agreement is amended, which we can provide no assurances will occur.
−Removed: In December 2019, we entered into the Aspire Agreement with Aspire Capital.
−Removed: Pursuant to this agreement, we may issue up to $20.0 million of shares of our common stock from time to time.
−Removed: Through March 13, 2019 , we had issued an aggregate of 4,757,544 shares of common stock under the Aspire Agreement, which amount includes approximately (i) 959,079 shares of common stock issued to Aspire Capital as consideration for its commitment to purchase shares of our common stock under the Aspire Agreement, (ii) 1,598,465 shares of common stock issued to Aspire Capital for an aggregate sale price of $1.0 million as an initial purchase under the Aspire Agreement, or the Initial Purchase Shares, and (iii) 2,200,000 shares of common stock issued to Aspire Capital for an aggregate sale price of $4.1 million as purchase shares under the terms of the Aspire Agreement.
−Removed: In February 2020, we entered into the 2020 Underwriting Agreement with the Underwriter.
−Removed: Pursuant to the 2020 Underwriting Agreement, the Underwriter purchased 15,000,000 shares of our common stock and warrants to purchase 7,500,000 shares of our common stock.
−Removed: Each whole warrant has an exercise price of $1.10 per share, was exercisable immediately and expires on the fifth anniversary of the date of issuance.
−Removed: Though the shares of common stock and warrants were sold together as a fixed combination, each consisting of one share of our common stock and one-half warrant, with each whole warrant exercisable to purchase one whole share of our common stock, the shares of our common stock and warrants were issued separately and were immediately separable upon issuance.
−Removed: The combined price to the public in the 2020 Public Offering for each share of common stock and accompanying one-half warrant was $1.00 , which resulted in approximately $14.0 million of net proceeds to us after deducting underwriting commissions and discounts and other estimated offering expenses payable by us and excluding the proceeds, if any, from the exercise of the warrants.
−Removed: If the warrants are exercised in the future, our stockholders may experience additional dilution, which could cause our stock price to fall.
In addition, pursuant to our Equity Incentive Plans, we may grant equity awards and issue additional shares of our Common Stock to our employees, directors, and consultants, and the number of shares of our Common Stock reserved for future issuance under certain of these plans will be subject to automatic annual increases in accordance with the terms of the plans.
6 unchanged sentences
This may prevent or discourage unsolicited acquisition proposals or offers for our Common Stock that you may believe are in your best interest as one of our stockholders.
+Added: Table of Con t ents
+Added: General Risk Factors
+Added: The market price of our Common Stock has historically been volatile, and the market price of our Common Stock may drop in the future.
+Added: The market price of our Common Stock has been, and may continue to be, subject to significant fluctuations.
+Added: Market prices for securities of early-stage pharmaceutical, biotechnology, and other life sciences companies have historically been particularly volatile.
+Added: Some of the factors that may cause the market price of our Common Stock to fluctuate include:
+Added: • our ability to obtain regulatory approvals for our product candidates, and delays or failures to obtain such approvals;
+Added: • failure of any of our product candidates, if approved, to achieve commercial success;
+Added: • failure to maintain our existing third-party license and supply agreements;
+Added: • changes in laws or regulations applicable to our product candidates;
+Added: • any inability to obtain adequate supply of our product candidates or the inability to do so at acceptable prices;
+Added: • adverse regulatory authority decisions;
+Added: • introduction of new products, services, or technologies by our competitors;
+Added: • failure to meet or exceed financial and development projections we may provide to the public and the investment community;
+Added: • the perception of the pharmaceutical industry by the public, legislatures, regulators, and the investment community;
+Added: • announcements of significant acquisitions, strategic collaborations, joint ventures, or capital commitments by us or our competitors;
+Added: • disputes or other developments relating to proprietary rights, including patents, litigation matters, and our ability to obtain patent protection for our technologies;
+Added: • additions or departures of key personnel;
+Added: • significant lawsuits, including patent or stockholder litigation;
+Added: • if securities or industry analysts do not publish research or reports about our business, or if they issue an adverse or misleading opinion regarding our business and stock;
+Added: • changes in the market valuations of similar companies;
+Added: • general market or macroeconomic conditions, including the ongoing COVID-19 pandemic;
+Added: • sales of our Common Stock by us or our stockholders in the future;
+Added: • trading volume of our Common Stock;
+Added: • announcements by commercial partners or competitors of new commercial products, clinical progress or the lack thereof, significant contracts, commercial relationships, or capital commitments;
+Added: • the introduction of technological innovations or new therapies that compete with our potential products;
+Added: • changes in the structure of health care payment systems;
+Added: • period-to-period fluctuations in our financial results.
+Added: Table of Con t ents
+Added: Moreover, the capital markets in general have experienced substantial volatility that has often been unrelated to the operating performance of individual companies, including as a result of the ongoing COVID-19 pandemic.
+Added: These broad market fluctuations may also adversely affect the trading price of our Common Stock.
+Added: In the past, following periods of volatility in the market price of a company’s securities, stockholders have often instituted class action securities litigation against those companies.
+Added: Such litigation, if instituted, could result in substantial costs and diversion of management attention and resources, which could significantly harm our profitability and reputation.
+Added: We incur costs and demands upon management as a result of complying with the laws and regulations affecting public companies.
+Added: We incur significant legal, accounting, and other expenses associated with public company reporting requirements.
+Added: We also incur costs associated with corporate governance requirements, including requirements under the Sarbanes-Oxley Act, as well as rules implemented by the SEC and The Nasdaq Stock Market LLC (“Nasdaq”).
+Added: These rules and regulations increase our legal and financial compliance costs and make some activities more time-consuming and costly.
+Added: These rules and regulations may also make it difficult and expensive for us to obtain directors’ and officers’ liability insurance.
+Added: As a result, it may be more difficult for us to attract and retain qualified individuals to serve on our board of directors or as our executive officers, which may adversely affect investor confidence and could cause our business or stock price to suffer.
If equity research analysts do not publish research or reports, or publish unfavorable research or reports, about us, our business, or our market, our stock price and trading volume could decline.
10 unchanged sentences
We may experience difficulty in meeting these reporting requirements in a timely manner for each period.
−Removed: Pursuant to Section 404(b) of the Sarbanes-Oxley Act, we are required to include in our Annual Reports on Form 10-K for the fiscal year ended December 31, 2019, and each following fiscal year in which we are an accelerated filer, an attestation report as to the effectiveness of our internal control over financial reporting that is issued by our independent registered public accounting firm unless another exemption to the attestation requirement is available to us.
−Removed: As we are required to include an attestation report in our Annual Reports on Form 10-K, we cannot guarantee that such an audit would not uncover a material weakness in our internal controls or a combination of significant deficiencies that could result in the conclusion that we have a material weakness in our internal controls because our independent registered public accounting firm has not yet attested as to the effectiveness of our internal control over financial reporting.
−Removed: Under rules of the SEC, a material weakness is defined as a deficiency, or a combination of deficiencies, in internal control over financial reporting such that there is a reasonable possibility that a material misstatement of a company’s annual or interim financial statements will not be prevented or detected on a timely basis.
−Removed: We cannot assure you that material weaknesses will not be identified in the future whether or not we are subject to the attestation requirements under Section 404(b) of the Sarbanes-Oxley Act.
We may discover weaknesses in our system of internal financial and accounting controls and procedures that could result in a material misstatement of our financial statements.
3 unchanged sentences
If we are not able to comply with the requirements of Section 404 of the Sarbanes-Oxley Act, or if we are unable to maintain proper and effective internal controls, it could result in a material misstatement of our financial statements that would not be prevented or detected on a timely basis, which could require a restatement, cause us to be subject to sanctions or investigations by Nasdaq, the SEC, or other regulatory authorities, cause investors to lose confidence in our financial information, or cause our stock price to decline.
−Removed: As a public company, we incur significant legal, accounting, insurance, and other expenses that we did not incur as a private company, and our management and other personnel have and will need to continue to devote a substantial amount of time to compliance initiatives resulting from operating as a public company.
−Removed: We also anticipate that these costs and compliance initiatives will increase in 2020 and other future periods as a result of ceasing to be an “emerging growth company,” as defined in the JOBS Act.
+Added: As a public company, we incur significant legal, accounting, insurance, and other expenses, and our management and other personnel have and will need to continue to devote a substantial amount of time to compliance initiatives resulting from
+Added: Table of Con t ents
+Added: operating as a public company.
+Added: We also anticipate that these costs and compliance initiatives will continue to increase as a result of ceasing to be an “emerging growth company,” as defined in the in the Jumpstart Our Business Startups Act of 2012.
UNRESOLVED STAFF COMMENTS
−Removed: We lease 27,128 square feet of office and laboratory space in Boulder, Colorado under a lease that expires in December 2020, subject to two three-year renewal options prior to the expiration, and that includes rent escalation clauses through the lease term.
−Removed: We believe that this space is suitable for our current needs.
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.