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In particular, risks associated with our business include:
−Removed: • Our prospects are highly dependent on the continued successful commercialization of NUPLAZID and DAYBUE.
−Removed: To the extent we cannot maintain or increase sales of NUPLAZID or DAYBUE, our business, financial condition and results of operations may be materially adversely affected and the price of our common stock may decline.
−Removed: • The terms of the FDA’s approval of NUPLAZID for the treatment of hallucinations and delusions associated with PDP may limit its commercial potential;
−Removed: both NUPLAZID and DAYBUE are subject to ongoing regulatory requirements.
−Removed: • We rely on a limited internal commercial team and a limited network of third-party distributors and pharmacies to market and sell NUPLAZID and DAYBUE.
−Removed: If this approach ceases to be effective, our commercialization of NUPLAZID and DAYBUE may be adversely affected, and NUPLAZID and DAYBUE may not be profitable.
−Removed: • If we do not obtain regulatory approval of trofinetide outside North America or for indications in addition to Rett syndrome, we will not be able to market trofinetide outside North America or for other indications in North America, which will limit our commercial revenues.
−Removed: • If we are unable to effectively train and equip our sales forces, our ability to successfully commercialize NUPLAZID and DAYBUE will be harmed.
−Removed: • NUPLAZID and DAYBUE may not gain maximal acceptance among physicians, patients, caregivers and the medical community, thereby limiting our potential to generate revenues.
−Removed: • Our ability to generate product revenues will be diminished if coverage for our products from payors is decreased or if patients have unacceptably high co-pay amounts.
−Removed: • Delays, suspensions and terminations in our clinical trials could result in increased costs to us and delay our ability to generate product revenues.
+Added: • Our prospects are highly dependent on the successful commercialization of our products.
+Added: To the extent we cannot maintain or increase sales of our products, our business, financial condition and results of operations may be materially adversely affected and the price of our common stock may decline.
+Added: • Our products may not gain maximal acceptance among physicians, patients, caregivers and the medical community, thereby limiting our potential to generate revenues.
+Added: • If we do not obtain regulatory approval of trofinetide outside North America, we will not be able to market trofinetide outside North America, which will limit our commercial revenues.
+Added: • Our ability to generate product revenues will be diminished if coverage for our products from commercial or government payors is decreased or if patients have unacceptably high out-of-pocket requirements.
+Added: • Our products are subject to ongoing regulatory requirements that could cause us significant expense and delay or limit our ability to generate sales revenues.
+Added: • We rely on a limited network of third-party distributors and pharmacies to market and sell our products.
+Added: If this approach ceases to be effective, commercialization of our products may be adversely affected, and our products may not be profitable.
+Added: • Drug development is a long, expensive and unpredictable process with a high risk of failure, and there is no guarantee that our products or product candidates will be successful in ongoing or future clinical trials or obtain regulatory approval.
+Added: • Expanded access or compassionate use programs could subject us to additional risks.
+Added: • Delays, suspensions and terminations in our clinical trials for our product candidates could result in increased costs to us and delay our ability to generate product revenues.
• If we are unable to attract, retain, and motivate key management, research and development, and sales and marketing personnel, our drug development programs, our research and discovery efforts, and our commercialization plans may be delayed and we may be unable to successfully commercialize our products, or develop our product candidates.
+Added: • If we fail to develop, acquire or in-license other product candidates or products, our business and prospects would be limited.
+Added: Even if we obtain rights to other product candidates or products, we will incur a variety of costs and may never realize the anticipated benefits.
• We have a history of net losses and we may not be able to predict the extent of future losses.
−Removed: • If we fail to generate capital, or otherwise obtain the capital necessary to fund our operations, we will be unable to successfully continue the commercialization of NUPLAZID and the development and commercialization of DAYBUE or successfully develop and commercialize our product candidates, if approved.
+Added: • We may require additional financing in the future to fund our operations.
+Added: If we cannot raise additional financing in the future, we may be unable to fund our business plan and our future research, development, commercial and manufacturing efforts.
• We expect that our results of operations will fluctuate, which may make it difficult to predict our future performance from period to period.
+Added: • Changes in tax laws or regulations that are applied adversely to us or our customers may have a material adverse effect on our business, cash flow, financial condition or results of operations.
+Added: • Our ability to use net operating loss carryforwards and certain other tax attributes to offset future taxable income or taxes may be limited.
+Added: • Tax authorities could reallocate our taxable income among our subsidiaries, which could increase our overall tax liability.
• Unfavorable global economic conditions could adversely affect our business, financial condition or results of operations.
−Removed: • We depend on collaborations with third parties to develop certain of our product candidates and may need to enter into future collaborations to develop and commercialize certain of our product candidates.
−Removed: • Our collaborations may be subject to conflicts or disputes, which could have a material adverse effect on our business, results of operations and financial condition.
−Removed: • We currently depend, and in the future will continue to depend, on third parties to manufacture NUPLAZID, DAYBUE and any product candidates.
−Removed: If these manufacturers fail to provide us or our collaborators with adequate supplies of clinical trial materials and commercial product or fail to comply with the requirements of regulatory authorities, we may be unable to develop or commercialize NUPLAZID, DAYBUE or any product candidates, if approved.
−Removed: • Our ability to compete may decline if we do not adequately protect our proprietary rights.
−Removed: • A dispute concerning the infringement or misappropriation of our proprietary rights or the proprietary rights of others could be time-consuming and costly, and an unfavorable outcome could harm our business.
−Removed: • Healthcare reform measures may negatively impact our ability to sell NUPLAZID, DAYBUE or our product candidates, if approved, profitably.
−Removed: • If our competitors develop and market products that are more effective than NUPLAZID, DAYBUE or our product candidates, if approved, they may reduce or eliminate our commercial opportunity.
−Removed: • Our stock price historically has been, and is likely to remain, highly volatile.
−Removed: Risks Related to Our Business
−Removed: Our prospects are highly dependent on the continued successful commercialization of NUPLAZID and DAYBUE.
−Removed: To the extent we cannot maintain or increase sales of NUPLAZID or DAYBUE, our business, financial condition and results of operations may be materially adversely affected and the price of our common stock may decline.*
−Removed: In March 2023 and October 2024, we announced FDA and Health Canada approval, respectively, of DAYBUE for the treatment of Rett syndrome in adult and pediatric patients two years of age and older, and DAYBUE became available for prescription in the United States in April 2023.
−Removed: NUPLAZID has been approved in the U.S.
−Removed: since April 2016 for the treatment of hallucinations and delusions associated with PDP.
−Removed: The continued successful commercialization of NUPLAZID and DAYBUE is subject to many risks, and there is no guarantee that we will be able to maintain or increase sales of NUPLAZID and DAYBUE.
−Removed: There are numerous examples of failures to meet high expectations of market potential, including by pharmaceutical companies with more experience and resources than us.
−Removed: While we have established our commercial teams and have hired our U.S.
−Removed: sales forces for each of NUPLAZID and DAYBUE, we may need to further expand and develop our DAYBUE commercial team and sales force as we pursue approval of DAYBUE in other indications and in other jurisdictions.
−Removed: Even if we are successful in expanding and developing our DAYBUE commercial team and sales force, there are many factors that could negatively impact the sales of our products or cause the continued commercialization of our products to be unsuccessful, including a number of factors that are outside our control.
−Removed: The continued commercial success of NUPLAZID and DAYBUE currently depends on the extent to which patients, caregivers and physicians recognize and diagnose the indications for which NUPLAZID and DAYBUE are approved and accept and adopt NUPLAZID and DAYBUE as a treatment for such indications, and we do not know whether our or others’ estimates in this regard will be accurate.
−Removed: In addition, we have changed the price of NUPLAZID and DAYBUE in the past, and in the future we may change the price of NUPLAZID and DAYBUE from time to time.
−Removed: Physicians may not prescribe NUPLAZID or DAYBUE and patients may be unwilling to use NUPLAZID or DAYBUE, due to a number of factors, including if coverage is not provided, coverage changes in the future, reimbursement is inadequate to cover a significant portion of the cost, perception of each product’s clinical profile and clinical benefits or due to the prevalence and severity of any adverse side effects.
−Removed: Further, with respect to DAYBUE, especially because Rett syndrome is a rare disease with a small physician, patient, caregiver and medical community, the experiences of those adopting DAYBUE earlier could have significant impact on future adoption of DAYBUE by other physicians, patients and caregivers, either favorably or unfavorably, based on clinical benefits and side effects experienced.
−Removed: Thus, significant uncertainty remains regarding the commercial potential of DAYBUE.
−Removed: Additionally, any negative publicity related to NUPLAZID or DAYBUE, or negative development in our PMRs with respect to DAYBUE, in clinical development of DAYBUE in additional indications or in regulatory processes in other jurisdictions, may adversely impact our commercial results and potential of NUPLAZID or DAYBUE.
−Removed: Thus, significant uncertainty remains regarding the commercial potential of NUPLAZID and DAYBUE.
−Removed: If the commercialization of our products and future sales are less successful than expected or perceived as disappointing, our stock price could decline significantly and the long-term success of our products and our company could be harmed.
−Removed: The terms of the FDA’s approval of NUPLAZID for the treatment of hallucinations and delusions associated with PDP may limit its commercial potential;
−Removed: both NUPLAZID and DAYBUE are subject to ongoing regulatory requirements.*
−Removed: The scope and terms of the FDA’s approval of NUPLAZID may limit our ability to commercialize NUPLAZID and, therefore, our ability to generate substantial sales revenues.
−Removed: The FDA has approved NUPLAZID only for the treatment of hallucinations and delusions associated with PDP, with or without dementia.
−Removed: The label for NUPLAZID also contains a “boxed” warning that elderly patients with dementia-related psychosis (DRP) treated with antipsychotic drugs are at an increased risk of death, and that NUPLAZID is not approved for the treatment of patients with dementia who experience psychosis unless their hallucinations and delusions are related to Parkinson’s Disease.
−Removed: The “boxed ” warning may discourage physicians from prescribing NUPLAZID to patients diagnosed with PDP, including those with dementia.
−Removed: In connection with the FDA approval of DAYBUE, we agreed to the following PMRs:
−Removed: a clinical study of renal impairment in healthy volunteers, nonclinical carcinogenicity studies and nonclinical in vitro and clinical in vivo drug interaction studies.
−Removed: FDA has released us from one of the five PMRs.
−Removed: In addition, we have fulfilled one of the five PMRs.
−Removed: Of the remaining three PMRs, we have also completed one and we are awaiting FDA’s acknowledgement and acceptance of that completed PMR.
−Removed: The results of any post-marketing study may cause the FDA to update the label, request additional studies and/or require risk mitigation plans.
−Removed: The manufacturing processes, labeling, packaging, distribution, adverse event reporting, storage, advertising, promotion and recordkeeping for NUPLAZID and DAYBUE will also continue to be subject to extensive and ongoing regulatory requirements.
−Removed: These requirements include submissions of safety and other post-marketing information and reports, registration, as well as continued compliance with cGMPs, good clinical practices, international council for harmonization guidelines and good laboratory practices, each of which are regulations and guidelines enforced by the FDA for all of our nonclinical and clinical development and for any clinical trials that we conduct post-approval.
−Removed: Discovery of any issues post-approval, including any safety concerns, such as carcinogenicity, unexpected side effects or drug-drug interaction problems, adverse events of unanticipated severity or frequency, or concerns over misuse or abuse of the product, problems with the facilities where the product is manufactured, tested, packaged or distributed, or failure to comply with regulatory requirements, may result in, among other things, restrictions on NUPLAZID, DAYBUE or on us, including:
−Removed: • withdrawal of approval, addition of warnings or narrowing of the approved indication in the product label;
−Removed: • requirement of a Risk Evaluation and Mitigation Strategy to mitigate the risk of off-label use in populations where the FDA may believe that the potential risks of use may outweigh its benefits;
−Removed: • voluntary or mandatory recalls;
−Removed: • warning letters;
−Removed: • suspension of any ongoing clinical studies;
−Removed: • refusal by the FDA or other regulatory authorities to approve pending applications or supplements to approved applications filed by us, or suspension or revocation of product approvals;
−Removed: • restrictions on operations, including restrictions on the marketing or manufacturing of the product or the imposition of costly new manufacturing requirements;
−Removed: • seizure or detention, or refusal to permit the import or export of products.
−Removed: If any of these actions were to occur, we may have to discontinue the commercialization of NUPLAZID or DAYBUE, limit our sales and marketing efforts, conduct further post-approval studies, and/or discontinue or change any other ongoing or planned clinical studies, which in turn could result in significant expense and delay or limit our ability to generate sales revenues.
−Removed: As we continue to commercialize NUPLAZID and DAYBUE, each product is becoming available to a larger number of patients, and we do not know whether the results of NUPLAZID and DAYBUE use in such larger number of patients will be consistent with the results from our clinical studies.*
−Removed: As we continue to commercialize NUPLAZID and DAYBUE, each product is becoming available to a larger number of patients.
−Removed: We do not know whether the results, when a larger number of patients are exposed to NUPLAZID and DAYBUE, including results related to safety and efficacy, will be consistent with the results from the clinical studies of NUPLAZID and DAYBUE that served as the basis for their approval.
−Removed: New data relating to NUPLAZID and DAYBUE, including from adverse event reports and applicable post-marketing studies in the U.S., and from other ongoing clinical studies, may result in changes to the product label and may adversely affect sales, or result in withdrawal of NUPLAZID or DAYBUE from the market.
−Removed: The FDA and regulatory authorities in other jurisdictions may also consider the new data in reviewing DAYBUE marketing applications for indications other than Rett syndrome and/or in other jurisdictions, or impose additional post‑approval requirements.
−Removed: If any of these actions were to occur, it could result in significant expense and delay or limit our ability to generate sales revenues.
−Removed: We rely on a limited internal commercial team and a limited network of third-party distributors and pharmacies to market and sell NUPLAZID and DAYBUE.
−Removed: If this approach ceases to be effective, our commercialization of NUPLAZID and DAYBUE may be adversely affected, and NUPLAZID and DAYBUE may not be profitable.*
−Removed: We employ our own internal specialty sales forces to commercialize NUPLAZID and DAYBUE as part of our commercialization strategy in the U.S.
−Removed: If we receive marketing approval for trofinetide in any other indication, we may need to increase our U.S.
−Removed: sales force significantly, and also potentially expand our commercial, medical affairs and general and administrative support functions to support commercialization for that indication.
−Removed: In addition, in July 2023, we entered into an expanded license agreement with Neuren under which we have the exclusive worldwide rights to develop and commercialize trofinetide for Rett syndrome.
−Removed: If we obtain marketing approval outside the U.S.
−Removed: using those worldwide rights, we will need to establish one or more sales forces in the additional countries and expand operations to support any new market.
−Removed: Further, we will be competing with other pharmaceutical and biotechnology companies to recruit, hire, train and retain such personnel.
−Removed: These efforts will be expensive and time consuming, and we cannot be certain that we will be able to successfully expand, refine and further develop our sales forces and related functional teams.
−Removed: Additionally, our strategy in the U.S.
−Removed: includes distributing NUPLAZID and DAYBUE solely through a limited network of third-party specialty distributors and specialty pharmacies.
−Removed: While we have entered into agreements with each of these distributors and pharmacies to distribute NUPLAZID and DAYBUE in the U.S., they may not perform as agreed or they may terminate their agreements with us.
−Removed: Also, we may need to enter into agreements with additional distributors or pharmacies, and there is no guarantee that we will be able to do so on commercially reasonable terms or at all.
−Removed: In the event we are unable to maintain, or expand, if needed, our commercial teams, including our U.S.
−Removed: sales forces or any future sales forces in jurisdictions outside the U.S., or maintain and, if needed, expand, our network of third-party specialty distributors and specialty pharmacies, our ability to continue commercializing NUPLAZID and DAYBUE would be limited, and NUPLAZID and DAYBUE may not be profitable.
−Removed: If we do not obtain regulatory approval of trofinetide outside North America or for indications in addition to Rett syndrome, we will not be able to market trofinetide outside North America or for other indications in North America, which will limit our commercial revenues.*
−Removed: While trofinetide was approved in 2023 in the U.S.
−Removed: by the FDA, and in October 2024 in Canada by Health Canada, for the treatment of Rett syndrome in adult and pediatric patients two years of age and older, it has not been approved by the FDA or Health Canada for any other indications, and it has not been approved in any other jurisdiction for this indication or in any other jurisdiction for any other indication.
−Removed: In order to market trofinetide for other indications or in other jurisdictions, we must obtain regulatory approval for each of those indications and in each of the applicable jurisdictions, and we may never be able to obtain such approval.
−Removed: Approval of DAYBUE by the FDA or Health Canada for the treatment of Rett syndrome does not ensure that DAYBUE will be approved by the FDA or Health Canada for any other indication.
−Removed: For example, although pimavanserin was approved in 2016 in the U.S.
−Removed: by the FDA for the treatment of hallucinations and delusions associated with PDP, it has not been approved by the FDA since then for any other indications.
−Removed: The research, testing, manufacturing, packaging, labeling, approval, sale, import, export, marketing, and distribution of pharmaceutical product candidates are subject to extensive regulation by the FDA and other regulatory authorities in the U.S.
−Removed: and other countries, whose regulations differ from country to country.
−Removed: We will be required to comply with different regulations and policies of the jurisdictions where we seek approval for our product candidates, and we have not yet identified all of the requirements that we will need to satisfy to submit DAYBUE for approval for other indications or in other jurisdictions.
−Removed: This will require additional time, expertise and expense, including the potential need to conduct additional studies or development work for other jurisdictions beyond the work that we have conducted to support our existing approvals for DAYBUE.
−Removed: If we do not receive FDA or Health Canada
−Removed: marketing approval for DAYBUE for any other indication, we will never be able to commercialize DAYBUE for any other indication in the U.S.
−Removed: If we do not receive marketing approval for DAYBUE in other jurisdictions, we will never be able to commercialize DAYBUE in other jurisdictions.
−Removed: Even if we do receive additional regulatory approvals, we may not be successful in commercializing those opportunities.
−Removed: If the results or timing of regulatory filings, the regulatory process, regulatory developments, clinical trials or preclinical studies, or other activities, actions or decisions related to DAYBUE do not meet our or others’ expectations, the market price of our common stock could decline significantly and the long-term success of the product and our company could be harmed.
−Removed: If we are unable to effectively train and equip our sales forces, our ability to successfully commercialize NUPLAZID and DAYBUE will be harmed.*
−Removed: We are and will continue to be required to expend significant time and resources to train our sales forces to be credible, persuasive, and compliant with applicable laws in marketing NUPLAZID and DAYBUE to physicians and healthcare providers, and for NUPLAZID, long-term care facilities and other healthcare providers, as appropriate.
−Removed: In addition, we must ensure that consistent and appropriate messages about NUPLAZID and DAYBUE are being delivered to our potential customers by our sales forces.
−Removed: If we are unable to effectively train our sales forces and equip them with current, effective materials, including medical and sales literature to help them inform and educate potential customers about the benefits of NUPLAZID and DAYBUE, and their proper administration, our efforts to successfully commercialize NUPLAZID and DAYBUE, could be put in jeopardy, which would negatively impact our ability to generate product revenues.
−Removed: NUPLAZID and DAYBUE may not gain maximal acceptance among physicians, patients, caregivers and the medical community, thereby limiting our potential to generate revenues.*
−Removed: The degree of market acceptance by physicians, healthcare professionals, patients, caregivers and third-party payors of NUPLAZID, DAYBUE and any other product for which we obtain regulatory approval, and our profitability and growth, will depend on a number of factors, including:
+Added: • We or the third parties upon whom we depend may be adversely affected by catastrophic events, such as earthquakes, fires, or other natural disasters and our business continuity and disaster recovery plans may not adequately protect us from a serious disaster.
+Added: • We have incurred, and expect to continue to incur, significant costs as a result of laws, regulations and standards relating to various aspects of our business, including corporate governance, work force initiatives and other matters, and failure to comply with such laws, regulations and standards could adversely affect our business.
+Added: • Our business involves the use of hazardous materials, and we and our third-party manufacturers and suppliers must comply with environmental, health and safety laws and regulations, which can be expensive and restrict how we do, or interrupt our, business .
+Added: Risks Related to Our Products and Product Candidates
+Added: Our prospects are highly dependent on the successful commercialization of our products.
+Added: To the extent we cannot maintain or increase sales of our products, our business, financial condition and results of operations may be materially adversely affected and the price of our common stock may decline.
+Added: We have two products that are approved for commercialization in the U.S.:
+Added: NUPLAZID and DAYBUE.
+Added: The successful commercialization of such products is subject to many risks, and there is no guarantee that we will be able to maintain or increase sales of such products.
+Added: Our business, financial condition and results of operations may be materially adversely affected and the price of our common stock may decline because of many factors, some of which are outside our control, including, but not limited to, the following:
+Added: • the extent to which patients, caregivers and physicians recognize and diagnose the indications for which our products are approved and accept and adopt our products as a treatment for such indications;
+Added: • the scope and terms of the FDA’s approval of our products, including the inclusion of a boxed warning for NUPLAZID or other warnings and precautions for our products;
+Added: • physicians may not prescribe our products and patients may be unwilling to use our products, due to a number of factors, including if coverage is not provided, coverage changes in the future, reimbursement is inadequate to cover a significant portion of the cost, negative or changing perceptions of each product’s clinical profile and clinical benefits or due to the prevalence and severity of any adverse side effects;
+Added: • the experiences of those adopting our products earlier could have significant impact on future adoption of our products by other physicians, patients and caregivers, either favorably or unfavorably, based on clinical benefits and side effects experienced;
+Added: • any new clinical data, post-approval studies or real world results, including in jurisdictions other than the U.S., could result in the FDA making changes to the product label or withdrawal from the market, and could impact regulatory approvals for other indications in the U.S.
+Added: or other jurisdictions, if any, any of which could result in significant expense and delay or limit our ability to generate sales revenues;
+Added: • our products are becoming available to a larger number of patients and patients’ experiences and results with our products may not be consistent with, or may be more negative when compared to, the experiences and results of those treated in our clinical trials;
+Added: • successful expansion and development of our commercial team and sales forces;
+Added: • any negative publicity related to our products.
+Added: Additionally, our success is dependent on our ability to obtain regulatory approval for, and successfully commercialize, trofinetide in jurisdictions outside the U.S., including the EU.
+Added: We will face in jurisdictions outside the U.S., such as the EU, if approved for marketing, risks and uncertainties similar to the risks and uncertainties faced in the U.S.
+Added: with respect to commercialization outside of the U.S., including, but not limited to, government reimbursement of the cost of trofinetide.
+Added: If the commercialization of our products and future sales is less successful than expected or perceived as disappointing, our stock price could decline significantly and the long-term success of our products and our company could be harmed.
+Added: Our products may not gain maximal acceptance among physicians, patients, caregivers and the medical community, thereby limiting our potential to generate revenues.
+Added: The degree of market acceptance by physicians, healthcare professionals, patients, caregivers and third-party payors of our products, and our profitability and growth, will depend on a number of factors, including:
• the ability to provide acceptable evidence of safety and efficacy;
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• the availability of alternative treatments;
−Removed: • the willingness of the target patient population to try new therapies and of physicians to prescribe these therapies, and our ability to increase awareness of our approved products through marketing efforts;
+Added: • the willingness of the target patient population to try new therapies and of physicians to prescribe these therapies;
+Added: • our ability to increase awareness of our approved products through marketing efforts;
• pricing and cost effectiveness, which may be subject to regulatory control;
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If a product does not provide a treatment regimen that is at least as beneficial as the current standard of care or otherwise does not provide patient benefit, that product will not achieve market acceptance and will not generate sufficient revenues to achieve or maintain profitability.
−Removed: With respect to NUPLAZID and DAYBUE specifically, successful commercialization will depend on whether and to what extent physicians, patients, caregivers, long-term care facilities and pharmacies, over whom we have no control, determine to utilize NUPLAZID and DAYBUE.
−Removed: NUPLAZID is available to treat hallucinations and delusions associated with PDP, and DAYBUE is available to treat Rett syndrome, both indications for which no other FDA-approved pharmaceutical treatments currently exist.
−Removed: Because of this, it is particularly difficult to estimate NUPLAZID’s and DAYBUE’s market potential and how physicians, patients, caregivers, long-term care facilities and payors will respond to changes in the price of NUPLAZID and DAYBUE.
−Removed: Industry sources and analysts have a divergence of estimates for the near- and long-term market potential of NUPLAZID and DAYBUE, and a variety
−Removed: of assumptions directly impact the estimates for NUPLAZID’s and DAYBUE’s market potential, including assumptions regarding the prevalence of PDP and Rett syndrome, the rate of diagnosis of PDP and Rett syndrome, the prevalence and rate of hallucinations and delusions in patients diagnosed with PDP with respect to NUPLAZID, the rate of physician adoption of NUPLAZID and DAYBUE, the potential impact of payor restrictions regarding NUPLAZID and DAYBUE, and patient adherence and compliance rates.
−Removed: Small differences in these assumptions can lead to widely divergent estimates of the market potential of NUPLAZID and DAYBUE.
+Added: With respect to our products specifically, successful commercialization will depend on whether and to what extent physicians, patients, caregivers, long-term care facilities and pharmacies, over whom we have no control, determine to utilize our products.
+Added: NUPLAZID is available in the U.S.
+Added: to treat hallucinations and delusions associated with PDP, and DAYBUE is available in the U.S.
+Added: to treat Rett syndrome, both indications for which no other FDA-approved pharmaceutical treatments currently exist.
+Added: DAYBUE is also the first and only product approved in Canada for the treatment of Rett syndrome.
+Added: As there are no approved competitors for our products, it is particularly difficult to estimate the market potential for our products and how physicians, patients, caregivers, long-term care facilities and payors will respond to changes in the price of our products.
+Added: Industry sources and analysts have a divergence of estimates for the near- and long-term market potential of our products, and a variety of assumptions directly impact the estimates for our products’ market potential, including assumptions regarding the prevalence of PDP and Rett syndrome, the rate of diagnosis of PDP and Rett syndrome, the prevalence and rate of hallucinations and delusions in patients diagnosed with PDP with respect to NUPLAZID, the rate of physician adoption, the potential impact of payor restrictions, and patient adherence and compliance rates.
+Added: Small differences in these assumptions can lead to widely divergent estimates of the market potential of our products.
For example, with respect to NUPLAZID, certain research suggests that patients with Parkinson’s disease may be hesitant to report symptoms of PDP to their treating physicians for a variety of reasons, including apprehension about societal stigmas relating to mental illness.
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Further, NUPLAZID may take several weeks to show efficacy.
−Removed: Even if NUPLAZID is prescribed for the treatment of hallucinations and delusions associated with PDP, patients may stop taking NUPLAZID because they may not see results in the timeframe they desire.
+Added: Even if NUPLAZID is prescribed for the treatment of hallucinations and delusions associated with PDP, patients may stop taking NUPLAZID because they may not see results in the timeframe they desire or expect.
Similarly, even if DAYBUE is prescribed for the treatment of Rett syndrome, issues may arise with respect to patient acceptance, adherence, persistence and compliance rates for a variety of reasons, including due to the expected clinical benefits or expected and actual side effects a patient might incur.
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Additionally, if physicians or patients titrate DAYBUE below the recommended doses, patients may not experience the desired outcomes, and physicians or patients may develop negative beliefs about the effectiveness of DAYBUE and/or discontinue its use.
−Removed: The label for NUPLAZID also contains a “boxed” warning that elderly patients with DRP treated with antipsychotic drugs are at an increased risk of death, and that NUPLAZID is not approved for the treatment of patients with dementia who experience psychosis unless their hallucinations and delusions are related to Parkinson’s Disease.
+Added: The label for NUPLAZID also contains a “boxed” warning related to particularly important prescribing information, and the FDA reminded healthcare providers to be aware of the risks described in the NUPLAZID prescribing information following its observation of potentially concerning prescribing patterns.
There has also been attention to publicly reported deaths of patients that were prescribed NUPLAZID, and the FDA conducted an evaluation of available information about NUPLAZID.
−Removed: In the past, the FDA has observed potentially concerning prescribing patterns with NUPLAZID, such as the concomitant use of other antipsychotic drugs or drugs that can cause QT prolongation, a potential cause of heart rhythm disorder.
−Removed: The FDA reminded healthcare providers to be aware of the risks described in the NUPLAZID prescribing information and that none of the other antipsychotic medications are approved for the treatment of PDP.
−Removed: Regardless, perceptions that NUPLAZID is unsafe, even if unfounded, may discourage physicians from prescribing or patients from taking NUPLAZID.
−Removed: The commercial success of NUPLAZID and DAYBUE depends on acceptance by patients, caregivers and physicians, and there are a number of factors that could skew our or others’ estimates about prescribing behaviors and market adoption.
+Added: Perceptions that NUPLAZID is unsafe, even if unfounded, may discourage physicians from prescribing or patients from taking NUPLAZID.
+Added: The commercial success of our products depends on acceptance by patients, caregivers and physicians, and there are a number of factors that could skew our or others’ estimates about prescribing behaviors and market adoption.
If we fail to gain the acceptance of patients, caregivers and physicians, or if our estimates are inaccurate, these events could negatively impact our business, results of operations, financial condition and prospects.
−Removed: Our ability to generate product revenues will be diminished if coverage for our products from payors is decreased or if patients have unacceptably high out-of-pocket requirements.*
+Added: If we do not obtain regulatory approval of trofinetide outside North America, we will not be able to market trofinetide outside North America, which will limit our commercial revenues.
+Added: DAYBUE was approved in 2023 in the U.S.
+Added: by the FDA, and in October 2024 in Canada by Health Canada, for the treatment of Rett syndrome in adult and pediatric patients two years of age and older.
+Added: In January 2025, we submitted a marketing authorization application for the approval of trofinetide for the treatment of Rett syndrome in the EU.
+Added: If we do not receive marketing approval for trofinetide in the EU or other jurisdictions outside of North America, including Japan, we will never be able to commercialize trofinetide in such jurisdictions.
+Added: Even if we do receive additional regulatory approvals, we may not be successful in commercializing those opportunities.
+Added: If the results or timing of regulatory filings, the regulatory process, regulatory developments, clinical trials or preclinical studies, or other activities, actions or decisions related to DAYBUE or trofinetide do not meet our or others’ expectations, the market price of our common stock could decline significantly and the long-term success of the product and our company could be harmed.
+Added: Our ability to generate product revenues will be diminished if coverage for our products from commercial or government payors is decreased or if patients have unacceptably high out-of-pocket requirements.
Patients who are prescribed medicine for the treatment of their conditions generally rely on third-party payors, including governmental healthcare programs, such as Medicare and Medicaid, managed care organizations and commercial payors, among others, to reimburse all or part of the costs associated with their prescription drugs.
1 unchanged sentence
Coverage decisions may depend upon clinical and economic standards that disfavor drug products when lower cost therapeutic alternatives are already available or subsequently become available.
−Removed: Even with coverage for NUPLAZID, DAYBUE or other products we may market, the resulting reimbursement payment rates might not be adequate or may require out-of-pocket obligations, such as deductibles and co-pay or coinsurance payments, that patients find unacceptably high.
−Removed: Patients may not use NUPLAZID and DAYBUE if coverage is not provided or reimbursement is inadequate to cover a significant portion of its cost.
−Removed: In addition, the market for NUPLAZID and DAYBUE depends significantly on access to third-party payors’ drug formularies, or lists of medications for which third-party payors provide coverage and reimbursement.
+Added: Even with coverage for our products, the resulting reimbursement payment rates might not be adequate or may require out-of-pocket obligations, such as deductibles and co-pay or coinsurance payments, that patients find unacceptably high.
+Added: Patients may not use our products if coverage is not provided or reimbursement is inadequate to cover a significant portion of its cost.
+Added: In addition, the market for our products depends significantly on access to third-party payors’ drug formularies, or lists of medications for which third-party payors provide coverage and reimbursement.
The industry competition to be included in such formularies often leads to downward pricing pressures on pharmaceutical companies.
−Removed: Also, third-party payors may refuse to include a particular branded drug in their formularies or otherwise restrict patient access to a branded drug when a less costly alternative is available, even if not approved for the indication for which NUPLAZID and DAYBUE are approved.
+Added: Also, third-party payors may refuse to include a particular branded drug in their formularies or otherwise restrict patient access to a branded drug when a less costly alternative is available, even if not approved for the indication for which our products are approved.
+Added: Legislators, policymakers and healthcare insurance funds in the EU and the United Kingdom may continue to propose and implement cost-containing measures to keep healthcare costs down, particularly due to the financial strain that the COVID-19 pandemic placed on national healthcare systems of European countries.
+Added: These measures could include limitations on the prices we would be able to charge for product candidates that we may successfully develop and for which we may obtain regulatory approval or the level of reimbursement available for these products from governmental authorities or third-party payors.
+Added: Consequently, a downward trend in prices of medicinal products in some countries could contribute to similar downward trends elsewhere.
Third-party payors, whether governmental or commercial, whether in the U.S.
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The current environment is putting pressure on companies to price products below what they may feel is appropriate.
−Removed: Selling NUPLAZID or DAYBUE at less than an optimized price would impact our revenues and could impact our overall success as a company.
−Removed: We have changed, and may continue to change, the price of NUPLAZID or DAYBUE from time to time, however, we do not know if the price we have selected, or may select in the future, for NUPLAZID or DAYBUE is or will be the optimized price.
−Removed: Additionally, we do not know whether and to what extent third-party payors will react to any possible future changes in the price of NUPLAZID or DAYBUE.
+Added: Selling our products at less than an optimized price would impact our revenues and could impact our overall success as a company.
+Added: We have changed, and may continue to change, the price of our products from time to time, however, we do not know if the price we have selected, or may select in the future, for our products is or will be the optimized price.
+Added: Additionally, we do not know whether and to what extent third-party payors will react to any possible future changes in the price of our products.
In the U.S., no uniform policy of coverage and reimbursement for drug products exists among third-party payors.
+Added: Outside the U.S., reimbursement and healthcare payment systems vary significantly by country, and many countries have instituted price ceilings on specific products and therapies.
Further, one payor’s determination to provide coverage and reimbursement for a product does not ensure that other payors will also provide coverage and reimbursement for the product.
−Removed: Therefore, coverage and reimbursement for NUPLAZID and DAYBUE in the U.S.
−Removed: may differ significantly from payor to payor.
−Removed: As a result, the coverage determination process is often a time-consuming and costly process that will require us to provide scientific and clinical support for the use of NUPLAZID and DAYBUE to each payor separately, with no assurance that coverage will be obtained.
+Added: Therefore, coverage and reimbursement for our products both in the U.S.
+Added: and outside may differ significantly from payor to payor.
+Added: As a result, the coverage determination process is often a time-consuming and costly process that will require us to provide scientific and clinical support for the use of our products to each payor separately, with no assurance that coverage will be obtained.
Coverage policies and third-party payor reimbursement rates may change at any time.
2 unchanged sentences
In these markets, healthcare services and determination of a product’s pricing and reimbursement are impacted by government control.
−Removed: So, for present and future considerations, if we are unable to obtain coverage of, and adequate payment levels for, NUPLAZID, DAYBUE or any other products we may market to third-party payors, physicians may limit how much or under what circumstances they will prescribe or administer them and patients may decline to purchase them.
−Removed: This in turn could affect our ability to successfully commercialize NUPLAZID, DAYBUE or any other products we may market, and thereby adversely impact our profitability, results of operations, financial condition, and future success.
−Removed: We are solely responsible for the development and commercialization of pimavanserin and trofinetide.*
−Removed: We have full responsibility for the pimavanserin and trofinetide programs throughout the world.
−Removed: We expect our research and development costs for continued development of trofinetide to be substantial.
−Removed: We are currently undertaking ongoing development work for trofinetide.
−Removed: In the event of approval for additional indications or in jurisdictions outside North America, we would need to add significant resources, in order to further commercialize trofinetide, and to conduct the necessary sales and marketing activities, and to conduct further development activities.
−Removed: With respect to NUPLAZID, our current strategy is to continue to commercialize NUPLAZID for the treatment of hallucinations and delusions associated with PDP in the U.S.
−Removed: using our specialty sales force that are focused on promoting NUPLAZID to physicians who treat PDP patients, including neurologists, psychiatrists and long-term care physicians.
−Removed: With respect to DAYBUE, our current strategy is to continue to commercialize DAYBUE for the treatment of Rett syndrome in North America and other jurisdictions in which DAYBUE may be approved, if any, using our specialty sales force focused on promoting DAYBUE to physicians who treat Rett syndrome patients, including those at Centers of Excellence, high-volume institutions and in the community setting.
−Removed: In selected markets outside the U.S.
−Removed: in which DAYBUE may be approved, if any, we may choose to commercialize DAYBUE independently or by establishing one or more strategic alliances.
−Removed: Without future additional resources or collaboration partners in selected markets outside of the U.S.
−Removed: for DAYBUE, we might not be able to realize the full value of DAYBUE.
−Removed: Even though DAYBUE is approved for the treatment of Rett syndrome in adult and pediatric patients two years of age and older, a failure in a subsequent trofinetide study for another indication or any additional studies, or a failure in our post-marketing studies could harm our ability to successfully market DAYBUE for the treatment of Rett syndrome in adult and pediatric patients two years of age and older or could lead to it being withdrawn from the market.
−Removed: Although pimavanserin was approved in 2016 in the U.S.
−Removed: by the FDA for the treatment of hallucinations and delusions associated with PDP, it has not been approved by the FDA since then for any other indications.
−Removed: If we are unable to develop trofinetide for other indications or in other jurisdictions, we may not be able to maximize the potential of trofinetide and that could have a material adverse effect on our future revenues and our success as a company.
−Removed: Drug development is a long, expensive and unpredictable process with a high risk of failure.*
+Added: For example, the EU provides options for EU Member States to restrict the range of medicinal products for which their national health insurance systems provide reimbursement and to control the prices of medicinal products for human use.
+Added: An EU Member State may approve a specific price for the medicinal product, it may refuse to reimburse a product at the price set by the manufacturer or it may instead adopt a system of direct or indirect controls on the profitability of the company placing the medicinal product on the market.
+Added: Many EU Member States also periodically review their reimbursement procedures for medicinal products, which could have an adverse impact on reimbursement status.
+Added: Moreover, in order to obtain reimbursement for our products in some European countries, including some EU Member States, we may be required to compile additional data comparing the cost-effectiveness of our products to other available therapies in a Health Technology Assessment (HTA).
+Added: An HTA of medicinal products is becoming an increasingly common part of the pricing and reimbursement procedures in some EU Member States, including those representing the larger markets.
+Added: The HTA process is the procedure to assess therapeutic, economic and societal impact of a given medicinal product in the national healthcare systems of the individual country.
+Added: The outcome of an HTA will often influence the pricing and reimbursement status granted to these medicinal products by the competent authorities of individual EU Member States.
+Added: The extent to which pricing and reimbursement decisions are influenced by the HTA of the specific medicinal product currently varies between EU Member States.
+Added: In December 2021, Regulation No 2021/2282 on HTA, was adopted in the EU.
+Added: This regulation, which entered into application on January 12, 2025 and has a phased implementation, is intended to boost cooperation among EU Member States in assessing health technologies, including new medicinal products, and providing the basis for cooperation at EU level for joint clinical assessments in these areas.
+Added: This regulation permits EU Member States to use common HTA tools, methodologies, and procedures across the EU, working together in four main areas, including joint clinical assessment of the innovative health technologies with the most potential impact for patients, joint scientific consultations whereby developers can seek advice from HTA authorities, identification of emerging health technologies to identify promising technologies early, and continuing voluntary cooperation in other areas.
+Added: Individual EU Member States continue to be responsible for assessing non-clinical (e.g., economic, social, ethical) aspects of health technologies, and making decisions on pricing and reimbursement.
+Added: So, for present and future considerations, if we are unable to obtain coverage of, and adequate payment levels for, our products we may market to third-party payors, physicians may limit how much or under what circumstances they will prescribe or administer them and patients may decline to purchase them.
+Added: This in turn could affect our ability to successfully commercialize our products or any other products we may market, and thereby adversely impact our profitability, results of operations, financial condition, and future success.
+Added: Our products are subject to ongoing regulatory requirements that could cause us significant expense and delay or limit our ability to generate sales revenues.*
+Added: In connection with the FDA approval of DAYBUE, we agreed to the following post-marketing requirements (PMRs):
+Added: a clinical study of renal impairment in healthy volunteers, nonclinical carcinogenicity studies and nonclinical in vitro and clinical in vivo drug interaction studies.
+Added: The FDA has released us from one of the five PMRs.
+Added: In addition, we have fulfilled one of the five PMRs.
+Added: Of the remaining three PMRs, we have completed one and are awaiting the FDA’s acknowledgement and acceptance.
+Added: The results of any post-marketing study may cause the FDA to update the label, request additional studies and/or require risk mitigation plans.
+Added: The manufacturing processes, labeling, packaging, distribution, adverse event reporting, storage, advertising, promotion and recordkeeping for our products will also continue to be subject to extensive and ongoing regulatory requirements in the U.S., Canada and in other foreign countries in which we operate, engage third-party manufacturers and obtain marketing approvals.
+Added: These requirements include submissions of safety and other post-marketing information and reports, registration, as well as continued compliance with cGMPs, licensing requirements, good clinical practices, international council for harmonization guidelines and good laboratory practices, each of which are regulations and guidelines enforced by regulatory authorities for all of our nonclinical and clinical development and for any clinical trials that we conduct post-approval.
+Added: Discovery of any issues post-approval, including any safety concerns, such as carcinogenicity, unexpected side effects or drug-drug interaction problems, adverse events of unanticipated severity or frequency, or concerns over misuse or abuse of the product, problems with the facilities where the product is manufactured, tested, packaged or distributed, or failure to comply with regulatory requirements, may result in, among other things, restrictions on our products or on us, including:
+Added: • withdrawal of approval, addition of warnings or narrowing of the approved indication in the product label;
+Added: • requirement of a Risk Evaluation and Mitigation Strategy to mitigate the risk of off-label use in populations where the FDA may believe that the potential risks of use may outweigh its benefits;
+Added: • voluntary or mandatory recalls;
+Added: • warning letters;
+Added: • suspension of any ongoing clinical studies;
+Added: • refusal by the FDA or comparable foreign regulatory authorities to approve pending applications or supplements to approved applications filed by us, or suspension or revocation of product approvals;
+Added: • restrictions on operations, including restrictions on the marketing or manufacturing of the product or the imposition of costly new manufacturing requirements;
+Added: • material fines or other types of penalties;
+Added: • seizure or detention, or refusal to permit the import or export of products.
+Added: If any of these actions were to occur, we may have to discontinue the commercialization of the applicable product, limit our sales and marketing efforts, conduct further post-approval studies, and/or discontinue or change any other ongoing or planned clinical studies, which in turn could result in significant expense and delay or limit our ability to generate sales revenues.
+Added: We rely on a limited network of third-party distributors and pharmacies to market and sell our products.
+Added: If this approach ceases to be effective, commercialization of our products may be adversely affected, and our products may not be profitable.
+Added: Our strategy includes distributing NUPLAZID in the U.S.
+Added: and DAYBUE or trofinetide, as applicable, in the U.S., Canada and other jurisdictions in which marketing is approved solely through a limited network of third-party specialty distributors, specialty pharmacies or other third-party partners.
+Added: While we have entered into agreements with each of these distributors and pharmacies to distribute NUPLAZID in the U.S.
+Added: and DAYBUE in the U.S.
+Added: and Canada, we will need to enter into similar agreements in any jurisdictions in which trofinetide is approved, and such distributors and pharmacies may not perform as agreed or they may terminate their agreements with us.
+Added: Also, we may need to enter into agreements with additional distributors, pharmacies or other entities, and there is no guarantee that we will be able to do so on commercially reasonable terms or at all.
+Added: In the event we are unable to maintain and, if needed, expand, our network of third-party specialty distributors and specialty pharmacies, our ability to continue commercializing our products would be limited, and our products may not be profitable.
+Added: Drug development is a long, expensive and unpredictable process with a high risk of failure, and there is no guarantee that our products or product candidates will be successful in ongoing or future clinical trials or obtain regulatory approval.
Preclinical testing and clinical trials are long, expensive and unpredictable processes that can be subject to delays.
−Removed: It may take several years to complete the preclinical testing and clinical development necessary to commercialize a drug, and delays or failure can occur at any stage.
Preliminary, initial, top-line or interim results of clinical trials do not necessarily predict final results and such results may change as more patient data becomes available and are subject to audit and verification procedures that could result in material changes in the final results.
1 unchanged sentence
A number of companies in the pharmaceutical and biotechnology industries have suffered significant setbacks in advanced clinical trials even after promising results in earlier trials.
−Removed: Our drug development programs are at various stages of development and the historical rate of failures for product candidates is extremely high.
−Removed: For example, we had an unsuccessful Phase 3 trial with NUPLAZID in 2009 and we have had several clinical studies evaluating pimavanserin in other indications that did not achieve statistical significance on certain endpoints, including the unsuccessful Phase 3 ADVANCE-2 study of pimavanserin for the treatment of the negative symptoms of schizophrenia in March 2024 and the unsuccessful Phase 2 study of pimavanserin for the treatment of irritability associated with autism spectrum disorder in pediatric populations (Pediatric Phase 2 Trial) in October 2024.
−Removed: At this time, we are not planning to conduct any additional clinical studies for pimavanserin.
−Removed: With the completion of the Pediatric Phase 2 Trial, we believe we have met the conditions of FDA’s written request to qualify for pediatric exclusivity for pimavanserin.
−Removed: However, there is no assurance that FDA will confirm that such conditions have been met and that the pediatric exclusivity will be granted.
−Removed: An unfavorable outcome in any of our ongoing or future development efforts or in the post-marketing studies for DAYBUE could be a major set-back for the programs and for us, generally.
−Removed: In particular, an unfavorable outcome in our DAYBUE program or in the post-marketing studies for DAYBUE, may require us to delay, devote additional substantial resources to, reduce the scope of, or eliminate the affected program and could have a material adverse effect on us and the value of our common stock.
−Removed: We are currently conducting several studies, including our Phase 2 study evaluating the efficacy and safety of an internally-developed compound known as ACP-204, which is akin to pimavanserin, as a potential treatment for the treatment of hallucinations and delusions associated with ADP and our Phase 3 COMPASS study evaluating the efficacy and safety of ACP-101 (intranasal carbetocin) for the treatment of hyperphagia in PWS and may conduct additional studies in the future.
−Removed: In connection with clinical trials, we face risks that:
+Added: Of the large number of product candidates in development, only a small percentage result in the submission of an NDA to the FDA or comparable regulatory filing to regulatory authorities in other jurisdictions, and even fewer are approved for marketing.
+Added: Even if clinical trials are completed, we or our collaborators may not submit applications for required authorizations to manufacture and/or market potential products or any such application may not be reviewed and approved by the appropriate regulatory authorities in a timely manner, if at all.
+Added: Our clinical trials face a number of risks, and our product candidates may fail regardless of whether our collaborators successfully complete the clinical trials and apply for such required authorizations for a number of reasons, including:
+Added: • a product candidate may fail to receive the regulatory clearances required to market them as drugs;
+Added: • a product candidate may be subject to proprietary rights held by others requiring the negotiation of a license agreement prior to marketing;
+Added: • a product candidate may be difficult or expensive to manufacture on a commercial scale;
+Added: • a product candidate may have adverse side effects that make their use less desirable;
+Added: • a product candidate may fail to compete with product candidates or other treatments commercialized by competitors;
• a product candidate may not prove to be efficacious or safe;
• patients may die or suffer other adverse effects for reasons that may or may not be related to the product candidate being tested;
−Removed: • the results may not be consistent with positive results of earlier trials;
−Removed: • the results may not meet the level of statistical significance required by the FDA or other regulatory agencies.
−Removed: If we do not successfully complete preclinical and clinical development, we will be unable to market and sell products derived from our product candidates and to generate product revenues.
−Removed: Even if we do successfully complete clinical trials, those results are not necessarily predictive of results of additional trials that may be needed before an NDA may be submitted to the FDA.
−Removed: Of the large number of drugs in development, only a small percentage result in the submission of an NDA to the FDA and even fewer are approved for commercialization.
−Removed: Delays, suspensions and terminations in our clinical trials could result in increased costs to us and delay our ability to generate product revenues.*
+Added: • the results of clinical trials may not be consistent with positive results of earlier trials;
+Added: • the results of clinical trials may not meet the level of statistical significance required by the FDA or comparable foreign regulatory authorities.
+Added: Our drug development programs are at various stages of development and the historical rate of failures for product candidates in our industry is extremely high.
+Added: We have had several clinical studies evaluating pimavanserin that did not achieve statistical significance on certain endpoints, including the unsuccessful Phase 3 ADVANCE-2 study of pimavanserin for the treatment of the negative symptoms of schizophrenia in March 2024 and the unsuccessful Phase 2 study of pimavanserin for the treatment of irritability associated with autism spectrum disorder in pediatric populations (Pediatric Phase 2 Trial) in October 2024.
+Added: At this time, we are not planning to conduct any additional clinical studies for pimavanserin.
+Added: With the completion of the Pediatric Phase 2 Trial, we believe we now have completed the FDA’s requirements to qualify for a pediatric exclusivity for pimavanserin.
+Added: However, there is no assurance that FDA will confirm that such requirements have been met and that the pediatric exclusivity will be granted.
+Added: An unfavorable outcome in any of our ongoing or future development efforts for trofinetide or in the post-marketing studies for DAYBUE could be a major set-back for the programs and for us, generally.
+Added: In particular, an unfavorable outcome in our trofinetide programs or in the post-marketing studies for DAYBUE, may require us to delay, devote additional substantial resources to, reduce the scope of, or eliminate the affected program and could have a material adverse effect on us and the value of our common stock.
+Added: Also, although we have submitted a marketing application for the approval of trofinetide in the EU, there is no guarantee we will receive regulatory approval.
+Added: We are currently conducting several studies with our product candidates, including our Phase 2 study evaluating the efficacy and safety of an internally-developed compound known as ACP-204, as a potential treatment for the treatment of hallucinations and delusions associated with ADP and our Phase 3 COMPASS study evaluating the efficacy and safety of ACP-101 (intranasal carbetocin) for the treatment of hyperphagia in PWS and may conduct additional studies with these and other product candidates in the future.
+Added: We plan to initiate an additional Phase 2 study of ACP-204 in LBDP in the third quarter of 2025 and to initiate a Phase 2 study of ACP-711 in essential tremor in 2026.
+Added: Drug development is a long, expensive and unpredictable process.
+Added: Even if we do successfully complete clinical trials, those results are not necessarily predictive of results of additional trials that may be needed before a marketing application may be submitted to regulatory authorities.
+Added: If we are unable to develop, or obtain marketing approval for, or, if approved, successfully commercialize our product candidates, we may not be able to generate sufficient revenue and our business operations and financial performance may be materially and adversely affected.
+Added: Expanded access or compassionate use programs could subject us to additional risks.
+Added: We currently provide and may provide in the future access to unapproved products or product candidates outside of clinical trials through expanded access or compassionate use programs (sometimes referred to as right to try programs).
+Added: These patients generally have life-threatening illnesses for which there are no alternative therapies or they have exhausted all other available therapies.
+Added: There are a number of risks that we may face as a result of our expanded access or compassionate use programs.
+Added: For example, the risk for serious adverse events in certain of these patient populations is high, which, if those adverse events are determined (or perceived) to be drug-related, could have a negative impact on the safety profile of our products and product candidates and cause significant delays, result in an inability to successfully commercialize our products and materially harm our business.
+Added: In certain jurisdictions, we may be required to provide our products for free if we participate in expanded access or compassionate use programs in certain jurisdictions.
+Added: In other jurisdictions we may be required to return some or all of the revenue we may generate through our expanded access or compassionate use programs if the appropriate foreign regulatory authority ultimately does not approve our products or product candidates for marketing in the jurisdiction of our expanded access or compassionate use programs.
+Added: If this were to occur, it could materially and adversely affect our business operations and financial performance.
+Added: Delays, suspensions and terminations in our clinical trials for our product candidates could result in increased costs to us and delay our ability to generate product revenues.
The commencement of clinical trials can be delayed for a variety of reasons, including delays in:
3 unchanged sentences
• obtaining clearance from the FDA to commence clinical trials pursuant to an Investigational New Drug application;
−Removed: • obtaining approval to conduct clinical trials in countries outside the United States pursuant to evolving regional and local regulations (e.g., EU Clinical Trials Regulation (EU No.
+Added: • obtaining approval to conduct clinical trials in countries or jurisdictions outside the United States pursuant to evolving regional and local regulations (e.g., EU Clinical Trials Regulation (EU No.
• obtaining institutional review board approval to conduct a clinical trial at a prospective clinical trial site;
13 unchanged sentences
For example, as a result of the conflict between Ukraine and Russia, we experienced temporary delays in accessing historical records of certain clinical trial sites located in Russia.
−Removed: It is possible that future enrollment in future studies, could be impacted due to the same or similar geopolitical or macroeconomic developments.
+Added: It is possible that enrollment in future studies, could be impacted due to the same or similar geopolitical or macroeconomic developments.
If patients withdraw from our trials, miss scheduled doses or follow-up visits or otherwise fail to follow trial protocols, or if our trial results are otherwise disrupted or disputed due to such developments, the integrity of data from our trials may be compromised or not accepted by the FDA or other regulatory authorities, which would represent a significant setback for the applicable program.
3 unchanged sentences
Our success depends on our ability to attract, retain, and motivate highly qualified management, scientific, and commercial personnel.
−Removed: In particular, our development programs depend on our ability to attract and retain highly skilled development personnel, especially in the fields of CNS disorders, including neuropsychiatric and related disorders.
−Removed: We are currently hiring, and in the future we expect to need to continue to hire, additional personnel as we expand our research and development efforts for pimavanserin and trofinetide, and commercial activities for NUPLAZID and DAYBUE.
−Removed: We face competition for experienced management, scientists, clinical operations personnel, commercial and other personnel from numerous companies and academic and other research institutions across North America and other jurisdictions in which DAYBUE may be commercialized, if approved.
+Added: In particular, our development programs depend on our ability to attract and retain highly skilled development personnel, especially in the fields of CNS disorders and rare diseases.
+Added: We are currently hiring, and in the future we expect to need to continue to hire, additional personnel as we expand our research and development efforts for our products and product candidates, and commercial activities for our products.
+Added: We face competition for experienced management, scientists, clinical operations personnel, commercial and other personnel from numerous companies and academic and other research institutions across all jurisdictions in which our products may be commercialized.
Many of the other biotechnology and pharmaceutical companies with whom we compete for qualified personnel have greater financial and other resources, different risk profiles and longer histories in the industry than we do.
1 unchanged sentence
Some of these characteristics may be more appealing to high quality candidates than that which we have to offer.
−Removed: If we are unable to continue to attract and retain high quality personnel, the rate and success at which we can
−Removed: develop and commercialize products and product candidates, if approved, will be limited.
−Removed: If we are unable to attract and retain the necessary personnel, it will significantly impede our commercialization efforts for NUPLAZID and DAYBUE, and the achievement of our research and development objectives.
+Added: If we are unable to continue to attract and retain high quality personnel, the rate and success at which we can develop and commercialize products and product candidates, if approved, will be limited.
+Added: If we are unable to attract and retain the necessary personnel, it will significantly impede our commercialization efforts for our products, and the achievement of our research and development objectives.
In September 2024, Catherine Owen Adams became our new CEO, replacing our former CEO, Stephen R.
4 unchanged sentences
We do not carry “key person” insurance covering members of senior management.
−Removed: If we receive approval of NUPLAZID or DAYBUE in additional indications or in additional jurisdictions, we may need to continue to increase the size of our organization.
−Removed: We may encounter difficulties with managing our growth, which could adversely affect our results of operations.*
−Removed: As of September 30, 2024, we employed approximately 620 employees.
−Removed: Our current infrastructure may be inadequate to support our development and commercialization efforts and expected growth.
−Removed: Future growth will impose significant added responsibilities on members of management, including the need to identify, recruit, and integrate additional employees and retain existing employees, and may take time away from running other aspects of our business, including development and commercialization of our products and product candidates, if approved.
−Removed: Our future financial performance and our ability to commercialize NUPLAZID, DAYBUE and any product candidates that receive regulatory approval and to compete effectively will depend, in part, on our ability to manage any future growth effectively.
−Removed: In particular, we will need to support the training and ongoing activities of our sales forces.
−Removed: To that end, we must be able to:
−Removed: • manage our development efforts effectively;
−Removed: • integrate additional management, administrative and manufacturing personnel;
−Removed: • develop our marketing and sales organization;
−Removed: • maintain sufficient administrative, accounting and management information systems and controls.
−Removed: We may not be able to accomplish these tasks or successfully manage our operations and, accordingly, may not achieve our research, development, and commercialization goals.
−Removed: Our failure to accomplish any of these goals could harm our business, results of operations, financial condition and prospects.
+Added: Risks Related to Our Business
If we fail to develop, acquire or in-license other product candidates or products, our business and prospects would be limited.
Even if we obtain rights to other product candidates or products, we will incur a variety of costs and may never realize the anticipated benefits.
−Removed: A key element of our strategy is to develop, acquire or in-license businesses, technologies, product candidates or products that we believe are a strategic fit with our business.
−Removed: The success of this strategy depends in large part on the combination of our regulatory, development and commercial capabilities and expertise and our ability to identify, select and acquire or in-license clinically-enabled product candidates for the treatment of neurological disorders, or for therapeutic indications that complement or augment our current products and product candidates, or that otherwise fit into our development or strategic plans on terms that are acceptable to us.
+Added: Part of our corporate strategy is to develop, acquire or in-license businesses, technologies, product candidates or products that we believe are a strategic fit with our business.
+Added: The success of this strategy depends in large part on the combination of our regulatory, development and commercial capabilities and expertise and our ability to identify, select and acquire or in-license clinically-enabled product candidates for the treatment of CNS disorders and rare diseases, or for therapeutic indications that complement or augment our current products and product candidates, or that otherwise fit into our development or strategic plans on terms that are acceptable to us.
Identifying, selecting and acquiring or in-licensing promising product candidates requires substantial technical, financial and human resources expertise, and we may not be successful in identifying acquisition targets, completing proposed acquisitions and integrating any acquired businesses, technologies, services or products into our current infrastructure.
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If we are unable to identify, select and acquire or license suitable product candidates from third parties on terms acceptable to us, our business and prospects will be limited.
−Removed: In particular, if we are unable to add additional commercial products to our portfolio, we may not be able to successfully leverage our commercial organization that we have assembled for the marketing and sale of NUPLAZID and DAYBUE.
The process of integrating any acquired business, technology, service, or product may result in unforeseen operating difficulties and expenditures and may divert significant management attention from our ongoing business operations.
As a result, we will incur a variety of costs in connection with an acquisition and may never realize its anticipated benefits.
−Removed: Moreover, any product candidate we
−Removed: identify, select and acquire or license may require additional, time-consuming development or regulatory efforts prior to commercial sale, including preclinical studies, if applicable, and extensive clinical testing and approval by the FDA and applicable foreign regulatory authorities.
+Added: Moreover, any product candidate we identify, select and acquire or license may require additional, time-consuming development or regulatory efforts prior to commercial sale, including preclinical studies, if applicable, and extensive clinical testing and approval by the FDA and applicable foreign regulatory authorities.
All product candidates are prone to the risk of failure that is inherent in pharmaceutical product development, including the possibility that the product candidate will not be shown to be sufficiently safe and/or effective for approval by regulatory authorities.
−Removed: In addition, we cannot assure you that any such products that are approved will be manufactured or produced economically, successfully commercialized or widely accepted in the marketplace or be more effective or desired than other commercially available alternatives.
−Removed: In addition, if we fail to successfully commercialize and further develop NUPLAZID, DAYBUE or our product candidates, if approved, there is a greater likelihood that we will fail to successfully develop a pipeline of other product candidates, and our business and prospects would therefore be harmed.
+Added: In addition, any such products that are approved may not be manufactured or produced economically, successfully commercialized or widely accepted in the marketplace or be more effective or desired than other commercially available alternatives.
We have a history of net losses and we may not be able to predict the extent of future losses.*
We have experienced significant net losses since our inception.
−Removed: As of September 30, 2024, we had an accumulated deficit of approximately $2.3 billion.
+Added: As of March 31, 2025, we had an accumulated deficit of approximately $2.2 billion.
We expect to increase our expenses and other investments in the coming years as we fund our operations, in-licensing or acquisition opportunities, and capital expenditures.
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We expect that our revenues over the next few years will be entirely dependent on our ability to generate product sales.
−Removed: Substantially all of our revenues since May 2016 were from net product sales of NUPLAZID and DAYBUE.
−Removed: To the extent that we cannot generate significant revenues from the sale of NUPLAZID and DAYBUE to cover our expenses, including the significant expenses associated with commercializing NUPLAZID and DAYBUE and continuing to develop trofinetide in additional indications and jurisdictions outside the U.S., we may not achieve profitability and/or may have to reduce our commercialization and/or research and development activities to become profitable, which would harm our future growth prospects.
+Added: Substantially all of our revenues since May 2016 were from U.S.
+Added: net product sales of NUPLAZID and DAYBUE.
+Added: To the extent that we cannot generate significant revenues from the sale of our products to cover our expenses, including the significant expenses associated with commercializing our products and continuing to develop trofinetide in additional indications and jurisdictions outside the U.S., we may not achieve profitability and/or may have to reduce our commercialization and/or research and development activities to become profitable, which would harm our future growth prospects.
Additionally, to obtain revenues from our product candidates, if approved, we must succeed, either alone or with others, in developing, obtaining regulatory approval for, manufacturing and marketing compounds with significant market potential.
We may never succeed in these activities and may never generate revenues that are significant enough to achieve profitability.
−Removed: If we fail to generate capital, or otherwise obtain the capital necessary to fund our operations, we will be unable to successfully continue the commercialization of NUPLAZID and the development and commercialization of DAYBUE or successfully develop and commercialize our product candidates, if approved.*
−Removed: We have consumed substantial amounts of capital since our inception.
−Removed: Our cash, cash equivalents, and investment securities totaled $565.3 million at September 30, 2024.
−Removed: While we believe that our existing cash resources will be sufficient to fund our cash requirements through at least the next twelve months, we may require additional financing in the future to continue to fund our operations.
+Added: We may require additional financing in the future to fund our operations.
+Added: If we cannot raise additional financing in the future, we may be unable to fund our business plan and our future research, development, commercial and manufacturing efforts.*
+Added: We have funded our operations primarily with revenues from sales of our products since their approvals, and through sales of our equity securities and interest income.
+Added: We anticipate that the level of cash used in our operations will fluctuate in future periods depending on the levels of spending required for our ongoing and planned commercial activities for our products, our ongoing and planned development activities for ACP-101 as a treatment for PWS and ACP-204 as a treatment for ADP, studies to be conducted pursuant to our PMRs, our ongoing and planned development activities for other early- and late-stage product candidates and strategic business development to further expand our portfolio.
+Added: We expect that our cash, cash equivalents and investment securities, as well as funds generated by anticipated sales of our products, will be sufficient to fund our planned operations through and beyond the next 12 months.
+Added: We may require additional financing in the future to fund our operations.
Our future capital requirements will depend on, and could increase significantly as a result of, many factors, including:
−Removed: • the progress in, and the costs of, our ongoing and planned development activities for trofinetide;
−Removed: • the progress in, and the costs of, our ongoing and planned development activities for our early-stage pipeline programs and our product candidates;
−Removed: • the progress in, and the costs of, our ongoing and planned commercial activities for NUPLAZID and DAYBUE, including the maintenance and development of our sales and marketing capabilities;
−Removed: • the costs of establishing, or contracting for, sales and marketing capabilities for our product candidates, if approved;
−Removed: • the amount of product sales from NUPLAZID and DAYBUE;
−Removed: • the costs of preparing applications for regulatory approvals for DAYBUE in jurisdictions outside North America and in additional indications other than Rett syndrome, and for our product candidates, as well as the costs required to support review of such applications;
−Removed: • the costs of manufacturing and distributing NUPLAZID and DAYBUE for commercial use;
−Removed: • our ability to obtain regulatory approval for, and subsequently generate product sales from DAYBUE in jurisdictions outside North America or in additional indications other than Rett syndrome, our early-stage pipeline programs and any product candidates, if approved;
−Removed: • the costs of acquiring additional products, product candidates or research and development programs;
+Added: • the costs of acquiring additional product candidates or research and development programs;
• the scope, prioritization and number of our research and development programs;
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• our ability to enter into new collaboration and license agreements;
+Added: • the progress in, and the costs of, our ongoing and planned development activities for pimavanserin, post-marketing studies for DAYBUE to be conducted over the next several years, and ongoing and planned commercial activities for our products;
+Added: • the costs of our development activities for our product candidates;
+Added: • the costs of commercializing our products, including the maintenance and development of our sales and marketing capabilities;
+Added: • the costs of establishing, or contracting for, sales and marketing capabilities for our product candidates;
+Added: • the amount of U.S.
+Added: product sales from our products;
+Added: • the costs of preparing applications for regulatory approvals for DAYBUE in jurisdictions other than the U.S., for NUPLAZID in additional indications other than PDP and for other product candidates, as well as the costs required to support review of such applications;
+Added: • the costs of manufacturing and distributing our products for commercial use in the U.S.;
+Added: • our ability to obtain regulatory approval for, and subsequently generate product sales from our product candidates;
• the extent to which we are obligated to reimburse collaborators or collaborators are obligated to reimburse us for costs under collaboration agreements;
• the costs involved in filing, prosecuting, enforcing, and defending patent claims and other intellectual property rights;
−Removed: • the costs of maintaining or securing manufacturing arrangements and supply for clinical or commercial production of pimavanserin, trofinetide or other product candidates;
−Removed: • the costs associated with litigation, including the costs incurred in defending against any product liability claims that may be brought against us related to NUPLAZID and DAYBUE or our product candidates.
−Removed: Unless and until we can generate significant cash from our operations, we expect to satisfy our future cash needs through our existing cash, cash equivalents and investment securities, strategic collaborations, public or private sales of our securities, debt financings, grant funding, or by licensing all or a portion of our product candidates or technology.
+Added: • the costs of maintaining or securing manufacturing arrangements for clinical or commercial production of pimavanserin, trofinetide or other product candidates;
+Added: • the costs associated with litigation, including the costs incurred in defending against any product liability claims that may be brought against us related to our products.
In the past, periods of turmoil and volatility in the financial markets have adversely affected the market capitalizations of many biotechnology companies, and generally made equity and debt financing more difficult to obtain.
For example, as a result of geopolitical and macroeconomic developments, the global credit and financial markets have experienced extreme volatility and disruptions, including diminished liquidity and credit availability, declines in consumer confidence, declines in economic growth, increases in unemployment rates and uncertainty about economic stability.
−Removed: These events, coupled with other factors, may limit our access to additional financing in the future.
−Removed: This could have a material adverse effect on our ability to access sufficient funding.
−Removed: We cannot be certain that additional funding will be available to us on acceptable terms, or at all.
−Removed: If funds are not available, we will be required to delay, reduce the scope of, or eliminate one or more of our research or development programs or our commercialization efforts.
+Added: These events, coupled with other factors, may limit our access to additional financing in the future if needed, and could have a material adverse effect on our ability to access sufficient funding.
+Added: We cannot be certain that additional funding will be available to us on a timely basis, on acceptable terms, or at all.
+Added: If additional funds are not available, we will be required to delay, reduce the scope of, or eliminate one or more of our research or development programs or our commercialization efforts.
We also may be required to relinquish greater or all rights to product candidates at an earlier stage of development or on less favorable terms than we would otherwise choose.
−Removed: Additional funding, if obtained, may significantly dilute existing stockholders and could negatively impact the price of our stock.
+Added: Additional funding, if necessary and obtained, may significantly dilute existing stockholders and could negatively impact the price of our stock.
We expect that our results of operations will fluctuate, which may make it difficult to predict our future performance from period to period.*
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Some of the factors that could cause our operating results to fluctuate from period to period include:
−Removed: • the success of our commercialization of NUPLAZID in the U.S.
−Removed: for the treatment of hallucinations and delusions associated with PDP and DAYBUE in North America for the treatment of Rett syndrome;
−Removed: • the impact of geopolitical and macroeconomic developments, general political, health and economic conditions, as well as any related political or economic responses and counter-responses or otherwise by various global actors or the general effect on the global economy and supply chain, pandemics or epidemics, economic slowdowns, recessions, inflation, high interest rates and tightening of credit markets on our business;
+Added: • the success of our commercialization of our products;
+Added: • the impact of geopolitical and macroeconomic developments, international tariffs, general political, health and economic conditions, as well as any related political or economic responses and counter-responses or otherwise by various global
+Added: actors or the general effect on the global economy and supply chain, pandemics or epidemics, economic slowdowns, recessions, inflation, high interest rates and tightening of credit markets on our business;
• the status and cost of our PMRs for DAYBUE;
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• the effect of competing technologies and products and market developments;
−Removed: • the costs associated with litigation, including the costs incurred in defending against any product liability claims that may be brought against us related to NUPLAZID, DAYBUE or our product candidates;
+Added: • the costs associated with litigation, including the costs incurred in defending against any product liability claims that may be brought against us related to our products or our product candidates;
• general and industry-specific economic conditions.
We believe that comparisons from period to period of our financial results are not necessarily meaningful and should not be relied upon as indications of our future performance.
−Removed: From time to time, we provide guidance relating to our expectations for net sales of NUPLAZID and DAYBUE and certain expense line items based on estimates and the judgment of management.
+Added: From time to time, we provide guidance relating to our expectations for net sales of our products and certain expense line items based on estimates and the judgment of management.
If, for any reason, our actual net sales or expenses differ materially from our guidance, we may have to revise our previously announced financial guidance.
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and global financial markets and adverse macroeconomic developments.
−Removed: and global market and economic conditions have been, and continue to be, disrupted and volatile due to many factors, including material shortages and related manufacturing and supply chain challenges, geopolitical developments (as well as any related political or economic responses and counter-responses or otherwise by various global actors or the general effect on the global economy and manufacturing and supply chain), and the responses by central banking authorities to control inflation, among others.
+Added: and global market and economic conditions have been, and continue to be, disrupted and volatile due to many factors, including international tariffs, material shortages and related manufacturing and supply chain challenges, geopolitical developments (as well as any related political or economic responses and counter-responses or otherwise by various global actors or the general effect on the global economy and manufacturing and supply chain), and the responses by central banking authorities to control inflation, among others.
General business and economic conditions that could affect our business, financial condition or results of operations include fluctuations in economic growth, debt and equity capital markets, liquidity of the global financial markets, the availability and cost of credit, investor and consumer confidence, and the strength of the economies in which we, our collaborators, our manufacturers and our suppliers operate.
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For example, high inflation may result in increases in our operating costs (including our labor costs), reduced liquidity and limits on our ability to access credit or otherwise raise capital on acceptable terms, if at all.
−Removed: In addition, the U.S.
−Removed: Federal Reserve has raised interest rates in response to concerns about inflation, which coupled with reduced government spending and volatility in financial markets may have the effect of further increasing economic uncertainty and heightening these risks.
+Added: In addition, reduced government spending and volatility in financial markets may have the effect of further increasing economic uncertainty and heightening these risks.
Risks of a prolonged global economic downturn are particularly true in Europe, which is undergoing a continued severe economic crisis.
−Removed: A weak or declining economy could also strain our suppliers and manufacturers, possibly resulting in supply and clinical trial disruption.
+Added: A weak or declining economy
+Added: could also strain our suppliers and manufacturers, possibly resulting in supply and clinical trial disruption.
Any of the foregoing could harm our business and we cannot anticipate all of the ways in which the current economic climate and financial market conditions could adversely impact our business.
−Removed: Earthquake or fire damage to our facilities could delay our research and development efforts and adversely affect our business.
−Removed: Our headquarters and research and development facilities in San Diego are located in a seismic zone, and we face the possibility of one or more earthquakes, which could be disruptive to our operations and result in delays in our research and development efforts.
−Removed: In addition, while our facilities have not been adversely impacted by local wildfires, there is the possibility of future fires in the area.
−Removed: In the event of an earthquake or fire, if our facilities or the equipment in our facilities is significantly damaged or destroyed for any reason, we may not be able to rebuild or relocate our facilities or replace any damaged equipment in a timely manner and our business, financial condition, and results of operations could be materially and adversely affected.
−Removed: We do not have insurance for damages resulting from earthquakes.
−Removed: While we do have fire insurance for our property and equipment located in San Diego, any damage sustained in a fire could cause a delay in our research and development efforts and our results of operations could be materially and adversely affected.
+Added: We or the third parties upon whom we depend may be adversely affected by catastrophic events, such as earthquakes, fires or other natural disasters and our business continuity and disaster recovery plans may not adequately protect us from a serious disaster.
+Added: We depend on our employees, consultants, and CROs, as well as regulatory agencies and other parties, for the continued operation of our business.
+Added: While we maintain disaster recovery plans, those plans may not adequately protect us.
+Added: Despite any precautions that we or any third parties on whom we depend take for catastrophic events, including earthquakes, fires or other natural disasters, these events could result in significant disruptions to our research and development, clinical trials, manufacturing and the commercialization of our products.
+Added: Long-term disruptions in the infrastructure caused by these types of events, particularly involving geographies in which we or third parties on whom we depend have offices or manufacturing, distribution or clinical trial sites, could adversely affect our businesses.
+Added: Although we carry business interruption insurance policies and typically have provisions in our contracts that protect us in certain events, our coverage might not include or be adequate to compensate us for all losses that may occur.
+Added: Any catastrophic event affecting us or the third parties on whom we depend could have a material adverse effect on our business, results of operations, financial condition and prospect.
+Added: We have incurred, and expect to continue to incur, significant costs as a result of laws, regulations and standards relating to various aspects of our business, including corporate governance, work force initiatives and other matters, and failure to comply with such laws, regulations and standards could adversely affect our business.*
+Added: Laws, regulations and standards affecting various aspects of our business, including as a result of provisions of the Dodd-Frank Wall Street Reform and Consumer Protection Act that was enacted in July 2010, the provisions of the Sarbanes-Oxley Act of 2002 (SOX), rules adopted or proposed by the SEC and by The Nasdaq Stock Market and executive orders, have resulted in, and will continue to result in, significant costs to us as we evaluate the implications of these laws, regulations and standards and respond to their requirements.
+Added: Certain laws, regulations and standards are subject to varying interpretations in some cases due to their lack of specificity, and as a result, their application in practice may evolve over time as new guidance is provided by regulatory and governing bodies, which could result in continuing uncertainty regarding compliance matters and higher costs necessitated by ongoing revisions to disclosure, policies and governance practices.
+Added: For example, in the future, if we are not able to issue an evaluation of our internal control over financial reporting, as required, or we or our independent registered public accounting firm determine that our internal control over financial reporting is not effective, this shortcoming could have an adverse effect on our business and financial results and the price of our common stock could be negatively affected.
+Added: Further, new laws, regulations and standards could make it more difficult or more costly for us to operate our business, including obtaining certain types of insurance (such as director and officer liability insurance), and we may be forced to accept reduced policy limits and coverage or incur substantially higher costs to obtain the coverage that is the same or similar to our current coverage.
+Added: The impact of these events could also make it more difficult for us to attract and retain qualified persons to serve on our board of directors and board committees, and as our executive officers.
+Added: If we fail, or are perceived to fail, to comply with these laws, regulations and standards, our reputation may be harmed and we might be subject to litigation, sanctions, investigations or other regulatory proceedings, which would adversely affect our financial results and our business.
+Added: We cannot predict or estimate the total amount of the costs we may incur or the timing of such costs to comply with these laws, regulations and standards.
Our business involves the use of hazardous materials, and we and our third-party manufacturers and suppliers must comply with environmental, health and safety laws and regulations, which can be expensive and restrict how we do, or interrupt our, business.
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We do not currently carry hazardous waste insurance coverage.
+Added: Our management has broad discretion over the use of our cash and we may not use our cash effectively, which could adversely affect our results of operations.
+Added: Our management has significant flexibility in applying our cash resources and could use these resources for corporate purposes that do not increase our market value, or in ways with which our stockholders may not agree.
+Added: We may use our cash resources for corporate purposes that do not yield a significant return or any return at all for our stockholders, which may cause our stock price to decline.
Risks Related to Our Relationships with Third Parties
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We depend on collaborations with third parties to develop certain of our product candidates and may need to enter into future collaborations to develop and commercialize certain of our product candidates.
−Removed: For example, in July 2023, we entered into an expanded license agreement with Neuren under which we have the exclusive worldwide rights to develop and commercialize trofinetide for Rett syndrome and other indications and NNZ-2591 for Rett syndrome and Fragile X syndrome.
−Removed: In January 2022, we entered into a license and collaboration agreement with Stoke to discover, develop and commercialize novel RNA-based medicines for the potential treatment of severe and rare genetic neurodevelopmental diseases of the CNS.
−Removed: In addition, we may choose to rely on collaborations in the future for certain portions of our pimavanserin and trofinetide programs or other product candidates, or for the commercialization of DAYBUE in selected markets outside of the U.S.
+Added: In addition, we may choose to rely on collaborations in the future for our products or other product candidates, including for the commercialization of DAYBUE in selected markets outside of the U.S.
Our collaborators may fail to develop or effectively commercialize products using our product candidates, if approved, or technologies because they:
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Collaborations are complex and time-consuming to negotiate and document.
−Removed: We also will face competition in our search for new collaborators, if we seek a new partner for our pimavanserin or trofinetide programs or other programs.
Given the current economic and industry environment, it is possible that competition for new collaborators may increase.
−Removed: In addition, there have been a significant number of recent business combinations among large pharmaceutical companies that have resulted in a reduced number of potential future collaborators.
We may not be able to negotiate additional collaborations on a timely basis, on acceptable terms, or at all.
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While we believe that there are numerous alternative sources to provide these services, in the event that we seek such alternative sources, we may not be able to enter into replacement arrangements without delays, additional expenditures, or at all, any of which could negatively affect our business, results of operations, financial condition and prospects.
−Removed: Even if we or our collaborators successfully complete the clinical trials of product candidates, the product candidates may fail for other reasons.
−Removed: Of the large number of product candidates in development, only a small percentage result in the submission of an NDA to the FDA or comparable regulatory filing to regulatory authorities in other jurisdictions, and even fewer are approved for marketing.
−Removed: We cannot assure you that, even if clinical trials are completed, either we or our collaborators will submit applications for required authorizations to manufacture and/or market potential products or that any such application will be reviewed and approved by the appropriate regulatory authorities in a timely manner, if at all.
−Removed: Even if we or our collaborators successfully complete the clinical trials of product candidates and apply for such required authorizations, the product candidates, such as pimavanserin and trofinetide, may fail for other reasons, including the possibility that the product candidates will:
−Removed: • fail to receive the regulatory clearances required to market them as drugs;
−Removed: • be subject to proprietary rights held by others requiring the negotiation of a license agreement prior to marketing;
−Removed: • be difficult or expensive to manufacture on a commercial scale;
−Removed: • have adverse side effects that make their use less desirable;
−Removed: • fail to compete with product candidates or other treatments commercialized by competitors.
−Removed: We currently depend, and in the future will continue to depend, on third parties to manufacture NUPLAZID, DAYBUE and any product candidates.
−Removed: If these manufacturers fail to provide us or our collaborators with adequate supplies of clinical trial materials and commercial product or fail to comply with the requirements of regulatory authorities, we may be unable to develop or commercialize NUPLAZID, DAYBUE or any product candidates, if approved.*
+Added: We currently depend, and in the future will continue to depend, on third parties to manufacture our products and product candidates.
+Added: If these manufacturers fail to provide us or our collaborators with adequate supplies of clinical trial materials and commercial product or fail to comply with the requirements of regulatory authorities, we may be unable to develop or commercialize our products or product candidates, if approved.*
We have no manufacturing facilities and only limited experience as an organization in the manufacturing of drugs or in designing drug-manufacturing processes.
−Removed: We have contracted with third-party manufacturers to produce, in collaboration with us, NUPLAZID, DAYBUE and our product candidates.
+Added: We have contracted with third-party manufacturers to produce, in collaboration with us, our products and product candidates.
We have contracted with Patheon Pharmaceuticals Inc.
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However, we have not entered into any agreements with any alternate suppliers for 10 mg NUPLAZID drug product or NUPLAZID API.
−Removed: We may face delays or increased costs in our supply chain that could jeopardize the commercialization of NUPLAZID or DAYBUE.
+Added: We may face delays or increased costs in our supply chain that could jeopardize the commercialization of our products.
While we currently have sufficient API for both NUPLAZID and DAYBUE and NUPLAZID and DAYBUE finished products on hand to continue our commercial and clinical operations as planned, depending on the effects of geopolitical and macroeconomic developments and whether such developments cause disruptions, we may face such delays or costs in future years.
−Removed: If any third party in our supply or distribution chain for materials or finished product is adversely impacted by geopolitical and macroeconomic developments, as well as any related political or economic responses and counter-responses or otherwise by various global actors or the general effect on the global economy and supply chain, our supply chain may be disrupted, limiting our ability to manufacture, test and distribute NUPLAZID or DAYBUE for commercial sales and our product candidates for our clinical trials and research and development operations.
+Added: If any third party in our supply or distribution chain for materials or finished product is adversely impacted by geopolitical and macroeconomic developments, including rapid changes in U.S.
+Added: trade policy, such as the imposition of tariffs and trade barriers as well as potential retaliatory measures taken by other governments, our supply chain may be disrupted, limiting our ability to manufacture, test and distribute our products for commercial sales and our product candidates for our clinical trials and research and development operations.
For example, it takes approximately two years for our third-party manufacturers to produce DAYBUE API, and a supply chain disruption in DAYBUE API would cause delays or increased costs to us that could jeopardize the commercialization of DAYBUE.
−Removed: Even though we have agreements with third parties for the manufacture of NUPLAZID and DAYBUE, the FDA may not approve the facilities of such manufacturers, the manufacturers may not perform as agreed, or the manufacturers may terminate their agreements with us.
−Removed: If any of the foregoing circumstances occur, we may need to find alternative manufacturing facilities, which would significantly impact our ability to develop, maintain or obtain, as applicable, regulatory approval for or market NUPLAZID, DAYBUE or any product candidates.
−Removed: While we believe that there will be alternative sources available to manufacture NUPLAZID, DAYBUE and any product candidates, in the event that we seek such alternative sources, we may not be able to enter into replacement arrangements without delays or additional expenditures.
+Added: Even though we have agreements with third parties for the manufacture of our products, the FDA may not approve the facilities of such manufacturers, the manufacturers may not perform as agreed, or the manufacturers may terminate their agreements with us.
+Added: If any of the foregoing circumstances occur, we may need to find alternative manufacturing facilities, which would significantly impact our ability to develop, maintain or obtain, as applicable, regulatory approval for or market our products or product candidates.
+Added: While we believe that there will be alternative sources available to manufacture our products and product candidates, in the event that we
+Added: seek such alternative sources, we may not be able to enter into replacement arrangements without delays or additional expenditures.
We cannot estimate these delays or costs with certainty but, if they were to occur, they could cause a delay in our development and commercialization efforts, which would have a negative effect on our business, results of operations, financial condition and prospects.
−Removed: The manufacturers of NUPLAZID, DAYBUE and any other product candidates, including Patheon, Siegfried, Corden, FIS and CoreRx, are obliged to operate in accordance with FDA-mandated current good manufacturing practices (cGMPs), and we have limited control over the ability of third-party manufacturers to maintain adequate quality control, quality assurance and qualified personnel to ensure compliance with cGMPs.
−Removed: In addition, the facilities used by our third-party manufacturers to manufacture NUPLAZID and DAYBUE and any product candidates must be approved by the FDA pursuant to inspections that will be conducted prior to any grant of regulatory approval by the FDA.
+Added: The manufacturers of our products and product candidates, including Patheon, Siegfried, Corden, FIS and CoreRx, are obliged to operate in accordance with FDA-mandated current good manufacturing practices (cGMPs), and we have limited control over the ability of third-party manufacturers to maintain adequate quality control, quality assurance and qualified personnel to ensure compliance with cGMPs.
+Added: In addition, the facilities used by our third-party manufacturers to manufacture our products and product candidates must be approved by the FDA pursuant to inspections that will be conducted prior to any grant of regulatory approval by the FDA.
If any of our third-party manufacturers are unable to successfully manufacture material that conforms to our specifications and the FDA’s strict regulatory requirements, or pass regulatory inspection, they will not be able to secure or maintain approval for the manufacturing facilities.
−Removed: Additionally, a failure by any of our third-party manufacturers to establish and follow cGMPs or to document their adherence to such practices may lead to significant delays in clinical trials or in obtaining regulatory approval of product candidates, or result in issues maintaining regulatory approval of NUPLAZID, DAYBUE and any product candidate that receives regulatory approval, negatively impact our commercialization of NUPLAZID or DAYBUE, or lead to significant delays in the launch and commercialization of any other products we may have in the future.
+Added: Additionally, a failure by any of our third-party manufacturers to establish and follow cGMPs or to document their adherence to such practices may lead to significant delays in clinical trials or in obtaining regulatory approval of product candidates, or result in issues maintaining regulatory approval of our products and any product candidate that receives regulatory approval, negatively impact our commercialization of our products, or lead to significant delays in the launch and commercialization of any other products we may have in the future.
Failure by our third-party manufacturers or us to comply with applicable regulations could result in sanctions being imposed on us, including fines, injunctions, civil penalties, failure of regulatory authorities to grant pre-market approval of drugs, delays, suspension or withdrawal of approvals, seizures or recalls of products, operating restrictions, and criminal prosecutions.
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These problems include difficulties with production costs and yields, quality control, including stability of the product, quality assurance testing, shortages of qualified personnel, as well as compliance with strictly enforced federal, state and foreign regulations.
−Removed: We cannot assure you that any issues relating to the manufacture of NUPLAZID, DAYBUE or any product candidates will not occur in the future.
+Added: We cannot assure you that any issues relating to the manufacture of our products or product candidates will not occur in the future.
Additionally, our manufacturers may experience manufacturing difficulties due to resource constraints or as a result of labor disputes 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 commercialize NUPLAZID or DAYBUE, or provide pimavanserin, trofinetide or any other product candidates to patients in clinical trials, would be jeopardized.
−Removed: Any delay or interruption in our ability to meet commercial demand for NUPLAZID, DAYBUE and any other approved products will result in the loss of potential revenues and could adversely affect our ability to gain market acceptance for these products.
+Added: If our manufacturers were to encounter any of these difficulties, or otherwise fail to comply with their contractual obligations, our ability to commercialize our products, or provide our products or product candidates to patients in clinical trials, would be jeopardized.
+Added: Any delay or interruption in our ability to meet commercial demand for our products and any other approved products will result in the loss of potential revenues and could adversely affect our ability to gain market acceptance for these products.
In addition, 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: Failures or difficulties faced at any level of our supply chain could materially adversely affect our business and delay or impede the development and commercialization of NUPLAZID, DAYBUE or any product candidates, if approved, and could have a material adverse effect on our business, results of operations, financial condition and prospects.
+Added: Failures or difficulties faced at any level of our supply chain could materially adversely affect our business and delay or impede the development and commercialization of our products or product candidates, if approved, and could have a material adverse effect on our business, results of operations, financial condition and prospects.
+Added: Further, changes in federal policy could affect the geopolitical landscape and could give rise to circumstances that negatively affect our business.
+Added: The third parties that manufacture our products and product candidates have manufacturing activities located in Canada, Europe and Switzerland.
+Added: has implemented, and has proposed to further implement, tariffs that may affect the availability of imported raw materials used in the production of our products and/or increase the costs of our third-party manufacturers and the expense to us to produce our products and product candidates.
+Added: Additionally, other governments have enacted, and may continue to enact, retaliatory measures in response to such tariffs.
+Added: If such actions were to materially affect us or our third-party manufacturers, we may not be able to successfully commercialize our products, which would have an adverse effect on our results of operations.
We may not be able to continue or fully exploit our collaborations with outside scientific and clinical advisors, which could impair the progress of our clinical trials and our research and development efforts.
−Removed: We work with scientific and clinical advisors at academic and other institutions who are experts in the field of CNS disorders.
+Added: We work with scientific and clinical advisors at academic and other institutions who are experts in the field of CNS disorders and rare diseases.
They assist us in our research and development efforts and advise us with respect to our clinical trials.
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Our ability to compete may decline if we do not adequately protect our proprietary rights.
−Removed: Our commercial success depends on obtaining and maintaining intellectual property rights to our products and product candidates, including NUPLAZID and DAYBUE, and technologies, as well as successfully defending these rights against third-party challenges.
+Added: Our commercial success depends on obtaining and maintaining intellectual property rights to our products and product candidates and technologies, as well as successfully defending these rights against third-party challenges.
Successful challenges to, or misappropriation of, our intellectual property could enable competitors to quickly duplicate or surpass our technological achievements, thus eroding our competitive position in our market.
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In addition, potential competitors have in the past and may in the future file an Abbreviated New Drug Application (ANDA) with the FDA for generic versions of NUPLAZID, seeking approval prior to the expiration of our patents.
−Removed: In response, we have filed complaints against these companies alleging infringement of certain of our Orange Book-listed patents covering NUPLAZID.
−Removed: For a more detailed description of these matters, see section captioned “Legal Proceedings” elsewhere in this report.
+Added: In response, we have filed complaints against these companies alleging infringement of certain of our Orange Book-listed patents covering NUPLAZID and DAYBUE.
+Added: For a more detailed description of these matters, see the section captioned “Legal Proceedings” elsewhere in this report.
While we intend to defend the validity of such patents vigorously, and will seek to use all appropriate methods to prevent their infringement, such efforts are expensive and time consuming.
−Removed: Any substantial decrease in the revenue and income derived from NUPLAZID or DAYBUE would have an adverse effect on our results of operations.
−Removed: With regard to patents, although we have filed numerous patent applications worldwide with respect to pimavanserin, not all of our patent applications resulted in an issued patent, or they resulted in an issued patent that is susceptible to challenge by a third party.
+Added: Any substantial decrease in the revenue and income derived from our products would have an adverse effect on our results of operations.
+Added: With regard to patents, although we control numerous patent applications worldwide with respect to pimavanserin and trofinetide, not all of our patent applications resulted in an issued patent, or they resulted in an issued patent that is susceptible to challenge by a third party.
Our ability to obtain, maintain , and/or defend our patents covering our product candidates and technologies is uncertain due to a number of factors, including:
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IPRs permit any person (except a party who has been litigating the patent for more than a year) to challenge the validity of the patent on the grounds that it was anticipated or made obvious by prior art.
−Removed: Patents covering pharmaceutical products have been subject to attack in IPRs from generic drug companies and from hedge funds.
+Added: covering pharmaceutical products have been subject to attack in IPRs from generic drug companies and from hedge funds.
If it is within nine months of the issuance of the challenged patent, a third party can petition the U.S.
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A patentee could prevent us from making, using or selling the patented compounds.
−Removed: In addition to the patent infringement lawsuits that we have recently initiated against the filers of ANDAs pertaining to NUPLAZID, we may need to resort to litigation to enforce other patents issued to us, protect our trade secrets or determine the scope and validity of third-party proprietary rights.
+Added: In addition to the patent infringement lawsuits against the filers of ANDAs pertaining to NUPLAZID, we may need to resort to litigation to enforce other patents issued to us, protect our trade secrets or determine the scope and validity of third-party proprietary rights.
From time to time, we may hire scientific personnel formerly employed by other companies involved in one or more areas similar to the activities conducted by us.
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In addition, during the course of this kind of litigation, there could be public announcements of the results of hearings, motions or other interim proceedings or developments.
−Removed: If securities analysts or investors perceive these results to be negative, it could have a substantial adverse effect on the trading price of our common stock.
+Added: Securities analysts and investors have in the past, and may again in the future perceive these results to be negative, it could have a substantial adverse effect on the trading price of our common stock.
The patent applications of pharmaceutical and biotechnology companies involve highly complex legal and factual questions, which, if determined adversely to us, could negatively impact our patent position.
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laws and those countries may lack adequate rules and procedures for defending our intellectual property rights.
−Removed: For example, some countries, including many in Europe, do not grant patent claims directed to methods of treating humans and, in these countries, patent protection may not be available at all to protect our product candidates.
+Added: For example, some countries, including many in Europe, do not grant patent claims directed to methods of treating humans and, in these countries, patent protection may not be available at all to protect our products and product candidates.
In addition, U.S.
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In both the U.S.
−Removed: and certain foreign jurisdictions, there have been a number of legislative and regulatory proposals to change the healthcare system in ways that could impact our ability to sell NUPLAZID, DAYBUE and any other potential products, as described in greater detail in the Government Regulation section of our Annual Report.
−Removed: For example, the Patient Protection and Affordable Care Act of 2010, as amended by the Health Care and Education Reconciliation Act of 2010 (collectively, the ACA), as well as other healthcare reform measures that may be adopted in the future, may result in more rigorous coverage criteria and in additional downward pressure on the price that we may receive for any approved product, including NUPLAZID and DAYBUE.
−Removed: With respect to pharmaceutical products, the ACA, among other things, expanded and increased industry rebates for drugs covered by Medicaid and made changes to the coverage requirements under Medicare Part D, Medicare’s prescription drug benefits program.
−Removed: There have been legal and political challenges to certain aspects of the ACA.
−Removed: Furthermore, on June 17, 2021, the U.S.
−Removed: Supreme Court dismissed a challenge on procedural grounds that argued the ACA is unconstitutional in its entirety because the “individual mandate” was repealed by Congress.
−Removed: Moreover, prior to the U.S.
−Removed: Supreme Court ruling, on January 28, 2021, President Biden issued an executive order that initiated a special enrollment period for purposes of obtaining health insurance coverage through the ACA marketplace, which began on February 15, 2021 and remained open through August 15, 2021.
−Removed: The executive order also instructed certain governmental agencies to review and reconsider their existing policies and rules that limit access to healthcare, including among others, reexamining Medicaid demonstration projects and waiver programs that include work requirements, and policies that create unnecessary barriers to obtaining access to health insurance coverage through Medicaid or the ACA.
−Removed: Further, on August 16, 2022, President Biden signed the Inflation Reduction Act of 2022 (IRA) into law, which among other things, extends enhanced subsidies for individuals purchasing health insurance coverage in ACA marketplaces through plan year 2025.
+Added: and certain foreign jurisdictions, there have been a number of legislative and regulatory proposals to change the healthcare system in ways that could impact our ability to sell our products, as described in greater detail in the Government Regulation section of this report.
+Added: For example, the Patient Protection and Affordable Care Act of 2010, as amended by the Health Care and Education Reconciliation Act of 2010 (collectively, the ACA), as well as other healthcare reform measures that may be adopted in the future, may result in more rigorous coverage criteria and in additional downward pressure on the price that we may receive for any of our approved products.
+Added: The ACA, among other things, expanded and increased industry rebates for drugs covered by Medicaid, made changes to the coverage requirements under Medicare Part D, Medicare’s prescription drug benefits program and broadened access to health insurance.
+Added: There have been legal and political challenges and amendments to certain aspects of the ACA.
+Added: For example, on August 16, 2022, the IRA was signed into law, which among other things, extends enhanced subsidies for individuals purchasing health insurance coverage in ACA marketplaces through plan year 2025.
The IRA also eliminates the “donut hole” under the Medicare Part D program beginning in 2025 by significantly lowering the beneficiary maximum out-of-pocket cost and through a newly established manufacturer discount program.
−Removed: It is possible that the ACA will be subject to judicial or Congressional challenges in the future.
−Removed: It is unclear how any such challenges and additional healthcare reform measures of the Biden administration will impact the ACA and our business.
+Added: It is possible that the ACA will be subject to additional challenges in
+Added: It is unclear how any such challenges and additional healthcare reform measures of the current administration will impact the ACA and our business.
Other legislative changes have been proposed and adopted in the U.S.
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Through the process created by the Budget Control Act of 2011, there are automatic reductions of Medicare payments to providers up to 2% per fiscal year, which went into effect in April 2013 and, due to subsequent legislative amendments, including the Infrastructure Investment and Jobs Act and the Consolidated Appropriations Act of 2023, will remain in effect through 2032 unless additional Congressional action is taken.
−Removed: In January 2013, President Obama signed into law the American Taxpayer Relief Act of 2012, which, among other things, further reduced Medicare payments to certain providers, and increased the statute of limitations period for the government to recover overpayments to providers from three to five years.
An expansion in the government’s role in the U.S.
−Removed: healthcare industry may increase existing congressional or governmental agency scrutiny on price increases, such as the ones we have implemented for NUPLAZID, cause general downward pressure on the prices of prescription drug products, lower reimbursements for providers using NUPLAZID, DAYBUE or any other product for which we obtain regulatory approval, reduce product utilization and adversely affect our business and results of operations.
+Added: healthcare industry may increase existing congressional or governmental agency scrutiny on price increases, such as the ones we have implemented for NUPLAZID, cause general downward pressure on the prices of prescription drug products, lower reimbursements for providers using our products, reduce product utilization and adversely affect our business and results of operations.
There have been several recent U.S.
presidential executive orders, 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: For example, in July 2021, the Biden administration released an executive order that included multiple provisions aimed at prescription drugs.
−Removed: In response to Biden’s executive order, on September 9, 2021, the U.S.
−Removed: Department of Health and Human Services (HHS) released a Comprehensive Plan for Addressing High Drug Prices that outlines principles for drug pricing reform.
−Removed: The plan sets out a variety of potential legislative policies that Congress could pursue as well as potential administrative actions HHS can take to advance these principles.
−Removed: In addition, the IRA, among other things, (1) directs HHS to negotiate the price of certain single-source drugs and biologics covered under Medicare and (2) imposes rebates under Medicare Part B and Medicare Part D to penalize price increases that outpace inflation.
−Removed: The IRA permits HHS to implement many of these provisions through guidance, as opposed to regulation, for the initial years.
+Added: For example, the IRA, among other things, (1) directs the U.S.
+Added: Department of Health and Human Services (HHS) to negotiate the price of certain single-source drugs that have been on the market for at least 7 years covered under Medicare (the Medicare Drug Price Negotiation Program) and (2) imposes rebates under Medicare Part B and Medicare Part D to penalize price increases that outpace inflation.
HHS has and will continue to issue and update guidance as these programs are implemented.
−Removed: These provisions take effect progressively starting in fiscal year 2023.
+Added: These provisions began to take effect progressively in fiscal year 2023.
On August 15, 2024, HHS announced the agreed-upon reimbursement prices of the first ten drugs that were subject to price negotiations, although the Medicare Drug Price Negotiation Program is currently subject to legal challenges.
HHS will select up to fifteen additional drugs covered under Part D for negotiation in 2025.
−Removed: Further, in response to the Biden administration’s October 2022 executive order, on February 14, 2023, HHS released a report outlining three new models for testing by the Centers for Medicare and Medicaid Services (CMS) Innovation Center which will be evaluated on their ability to lower the cost of drugs, promote accessibility, and improve quality of care.
−Removed: It is unclear whether the models will be utilized in any health reform measures in the future.
−Removed: On December 7, 2023, the Biden administration announced an initiative to control the price of prescription drugs through the use of march-in rights under the Bayh-Dole Act.
+Added: Each year thereafter more Part B and Part D products will become subject to the Medicare Drug Price Negotiation Program.
On December 8, 2023, the National Institute of Standards and Technology published for comment a Draft Interagency Guidance Framework for Considering the Exercise of March-In Rights which for the first time includes the price of a product as one factor an agency can use when deciding to exercise march-in rights.
While march-in rights have not previously been exercised, it is uncertain if that will continue under the new framework.
+Added: Further, the overall funding of certain government programs such as Medicaid and Medicare is uncertain and there is no guarantee that funds approved by the U.S.
+Added: Congress will be made available by the current administration.
+Added: We expect additional health reform measures may be implemented in the future, particularly in light of the recent U.S.
+Added: Presidential and Congressional elections.
+Added: The current administration is pursuing policies to reduce regulations and expenditures across government including at HHS, the FDA, the Centers for Medicare & Medicaid Services (CMS) and related agencies.
+Added: These actions, presently directed by executive orders or memoranda from the Office of Management and Budget, may propose policy changes that create additional uncertainty for our business.
+Added: These actions include, for example, directives to reduce agency workforce, program cuts, rescinding a Biden administration executive order tasking the Center for Medicare and Medicaid Innovation to consider new payment and healthcare models to limit drug spending and eliminating the Biden administration’s executive order that directed HHS to establish an AI task force and developing a strategic plan, directing HHS to lower prescription drug costs for Medicare through a variety of initiatives, including by improving upon the IRA, and directing certain federal agencies to enforce existing law regarding hospital and price plan transparency and by standardizing prices across hospitals and health plans.
+Added: Additionally, in its June 2024 decision in Loper Bright Enterprises v.
+Added: Raimondo , the U.S.
+Added: Supreme Court overturned the longstanding Chevron doctrine, under which courts were required to give deference to regulatory agencies’ reasonable interpretations of ambiguous federal statutes.
+Added: The Loper Bright decision could result in additional legal challenges to current regulations and guidance issued by federal agencies applicable to our operations, including those issued by the FDA.
+Added: Congress may introduce and ultimately pass health care related legislation that could impact the drug approval process and make changes to the Medicare Drug Price Negotiation Program created under the IRA.
Individual states in the U.S.
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Any such approved importation plans, if implemented, may result in lower drug prices for products covered by those programs.
−Removed: The implementation of cost-containment measures or other healthcare reforms may prevent us from being able to generate revenue, attain profitability, or commercialize NUPLAZID, DAYBUE or any other products for which we may receive regulatory approval.
+Added: The implementation of cost-containment measures or other healthcare reforms may prevent us from being able to generate revenue, attain profitability, or commercialize our products.
We are subject, directly and indirectly, to federal, state and foreign healthcare laws and regulations, including healthcare fraud and abuse laws, false claims laws, physician payment transparency laws and health information privacy and security laws.
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government-funded healthcare programs, such as Medicare and Medicaid, disgorgement, imprisonment, contractual damages, reputational harm, diminished profits, additional reporting requirements and/or oversight, and the curtailment or restructuring of our operations.
−Removed: Moreover, while we do not bill third-party payors directly and our customers make the ultimate decision on how to submit claims, from time-to-time, for NUPLAZID, DAYBUE and any product candidates that may be approved, we may provide reimbursement guidance to patients and healthcare providers.
+Added: Moreover, while we do not bill third-party payors directly and our customers make the ultimate decision on how to submit claims, from time-to-time, for our products, we may provide reimbursement guidance to patients and healthcare providers.
If a government authority were to conclude that we provided improper advice and/or encouraged the submission of a false claim for reimbursement, we could face action against us by government authorities.
−Removed: If any of the physicians or other providers or entities with whom we expect to do business is found to be not in compliance with applicable laws, they may be subject to criminal, civil or administrative sanctions, including exclusions from government-funded healthcare programs and imprisonment.
+Added: If any of the physicians, healthcare professions, or other providers or entities with whom we expect to do business is found to be not in compliance with applicable laws, they may be subject to criminal, civil or administrative sanctions, including exclusions from government-funded healthcare programs and imprisonment.
If any of the above occur, it could adversely affect our ability to operate our business and our results of operations.
−Removed: In addition, the approval and commercialization of NUPLAZID, DAYBUE or any product candidates that may be approved, outside the U.S.
−Removed: will also likely subject us to foreign equivalents of the healthcare laws mentioned above, among other foreign laws.
+Added: Outside the U.S., interactions between pharmaceutical companies and health care professionals are also governed by strict laws, such as national anti-bribery laws of European countries, national sunshine rules, regulations, industry self-regulation codes of conduct and physicians’ codes of professional conduct.
+Added: Failure to comply with these requirements could result in reputational risk, public reprimands, administrative penalties, fines or imprisonment, any of which could adversely affect our ability to operate our business and our results of operations.
We and the third parties with whom we work are subject to stringent and evolving U.S.
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For example, HIPAA, as amended by HITECH, imposes specific requirements relating to the privacy, security, and transmission of individually identifiable health information.
−Removed: Additionally, in the past few years, numerous U.S.
−Removed: states—including California, Virginia, Colorado, Connecticut, and Utah—have enacted comprehensive privacy laws that impose certain obligations on covered businesses, including providing specific disclosures in privacy notices and affording residents with certain rights concerning their personal data.
+Added: Additionally, numerous U.S.
+Added: states have enacted comprehensive privacy laws that impose certain obligations on covered businesses, including providing specific disclosures in privacy notices and affording residents with certain rights concerning their personal data.
As applicable, such rights may include the right to access, correct, or delete certain personal data, and to opt-out of certain data processing activities, such as targeted advertising, profiling, and automated decision-making.
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For example, the California Consumer Privacy Act of 2018 (CCPA) requires businesses to provide specific disclosures in privacy notices and honor requests of California residents to exercise certain privacy rights.
−Removed: The CCPA provides for fines of up to $7,500 per intentional violation and allows private litigants affected by certain data breaches to recover significant statutory damages.
+Added: The CCPA provides for fines for intentional violations and allows private litigants affected by certain data breaches to recover significant statutory damages.
Although some U.S.
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or private litigation related to processing of personal data brought by classes of data subjects or consumer protection organizations authorized at law to represent their interests.
−Removed: The Swiss Federal Act on Data Protection, or the FADP, also applies to the collection and processing of personal data, including health-related information, by companies located in Switzerland, or in certain circumstances, by companies located outside of Switzerland.
+Added: The Swiss Federal Act on Data Protection (FADP), also applies to the collection and processing of personal data, including health-related information, by companies located in Switzerland, or in certain circumstances, by companies located outside of Switzerland.
In addition, we may be unable to transfer personal data from Europe and other jurisdictions to the United States or other countries due to data localization requirements or limitations on cross-border data flows.
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In particular, the European Economic Area (EEA) and the UK have significantly restricted the transfer of personal data to the United States and other countries whose privacy laws it believes are inadequate.
−Removed: Other jurisdictions may adopt similarly stringent interpretations of their data localization and cross-border data transfer laws.
+Added: Other jurisdictions have adopted and may continue to adopt similarly stringent data localization and cross-border data transfer laws.
Although there are currently various mechanisms that may be used to transfer personal data from the EEA and UK to the United States in compliance with law, such as the EEA standard contractual clauses, the UK’s International Data Transfer Agreement / Addendum, and the EU-U.S.
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If we are unable to use generative AI, it could make our business less efficient and result in competitive disadvantages.
−Removed: In addition to data privacy and security laws, we may be contractually subject to industry standards adopted by industry groups and may become subject to such obligations in the future.
+Added: In addition to data privacy and security laws, we may be contractually subject to industry standards adopted by industry groups and may become subject to additional such obligations in the future.
We are also bound by other contractual obligations related to data privacy and security, and our efforts to comply with such obligations may not be successful.
−Removed: We publish privacy policies, marketing materials, and other statements, such as compliance with certain certifications or self-regulatory principles, regarding data privacy and security.
−Removed: If these policies, materials or statements are found to be deficient, lacking in transparency, deceptive, unfair, or misrepresentative of our practices, we may be subject to investigation, enforcement actions by regulators, or other adverse consequences.
+Added: We publish privacy policies, marketing materials, and other statements, such as statements related to compliance with certain certifications or self-regulatory principles, regarding artificial intelligence, data privacy and security.
+Added: Regulators in the United States are increasingly scrutinizing these statements, and if these policies, materials or statements are found to be deficient, lacking in transparency, deceptive, unfair, misleading or misrepresentative of our practices, we may be subject to investigation, enforcement actions by regulators, or other adverse consequences.
Additionally, under various privacy laws and other obligations, we may be required to obtain certain consents to process personal data.
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Invoicing for rebates is provided in arrears, and there is frequently a time lag of up to several months between the sales to which rebate notices relate and our receipt of those notices, which further complicates our ability to accurately estimate and accrue for rebates related to the Medicaid program as implemented by individual states.
−Removed: Thus, there can be no assurance that we will be able to identify all factors that may cause our discount and rebate payment obligations to vary from period to period, and our actual results may differ significantly from our estimated allowances for discounts and rebates.
+Added: Thus, we may not be able to identify all factors that may cause our discount and rebate payment obligations to vary from period to period, and our actual results may differ significantly from our estimated allowances for discounts and rebates.
Changes in estimates and assumptions may have a material adverse effect on our business, results of operations and financial condition.
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In addition, in the event that the CMS were to terminate our rebate agreement, no federal payments would be available under Medicaid or Medicare for our covered outpatient drugs.
−Removed: We could face liability if a regulatory authority determines that we are promoting NUPLAZID or DAYBUE for any “off-label” uses.
−Removed: A company may not promote “off-label” uses for its drug products.
−Removed: An off-label use is the use of a product for an indication or patient population that is not described in the product’s FDA-approved label in the U.S.
−Removed: or for uses in other jurisdictions that differ from those approved by the applicable regulatory agencies.
−Removed: Physicians, on the other hand, may prescribe products for off-label uses.
−Removed: Although the FDA and other regulatory agencies do not regulate a physician’s choice of drug treatment made in the physician’s independent medical judgment, they do restrict promotional communications from pharmaceutical companies or their sales force with respect to off-label uses of products for which marketing clearance has not been issued.
+Added: We could face liability if a regulatory authority determines that we are promoting our products for any “off-label” uses.
+Added: The FDA, Health Canada, the European Commission, competent authorities of individual EU Member States and other comparable foreign regulatory authorities and industry self-regulatory bodies strictly regulate the marketing and promotional claims that are made about drug and biologic products.
+Added: In particular, a company may not promote “off-label” uses for its drug products.
+Added: An off-label use is the use of a product for an indication, patient population, or manner that is not described in the product’s approved labeling and that differs from those approved by the applicable regulatory authorities.
+Added: Physicians and other persons qualified to prescribe medicinal products, on the other hand, may, in certain jurisdictions including the U.S., prescribe products for off-label uses.
+Added: Although the FDA and certain comparable foreign regulatory authorities do not generally regulate a physician’s or other person qualified to prescribe’s choice of drug treatment made in the such person’s independent medical judgment, they do restrict promotional communications from pharmaceutical companies or their sales force with respect to off-label uses of products for which marketing clearance has not been issued.
A company that is found to have promoted off-label use of its product may be subject to significant liability, including civil and criminal sanctions.
−Removed: We intend to comply with the requirements and restrictions of the FDA and other regulatory agencies with respect to our promotion of NUPLAZID, DAYBUE and any other products we may be approved to market, but we cannot be sure that the FDA or other regulatory agencies will agree that we have not violated their restrictions.
−Removed: As a result, we may be subject to criminal and civil liability.
−Removed: In addition, our management’s attention could be diverted to handle any such alleged violations.
+Added: We intend to comply with the requirements and restrictions of the FDA, Health Canada and other comparable foreign regulatory authorities, governmental authorities and regulatory bodies in the jurisdictions that approve our products or product candidates with respect to our promotion of our products, but such authorities may nevertheless make us the target of an investigation or prosecution based on our marketing and promotional practices.
+Added: As a result, we may be subject to criminal and civil liability for the promotion of off-label uses.
+Added: In addition, our management’s attention could be diverted to handle any such alleged violations, all of which could have a material adverse effect on our business, results of operations, financial condition and reputation.
A significant number of pharmaceutical companies have been the target of inquiries and investigations by various U.S.
−Removed: federal and state regulatory, investigative, prosecutorial and administrative entities in connection with the promotion of products for unapproved uses and other sales practices, including the Department of Justice (DOJ), and various U.S.
+Added: federal and state regulatory, investigative, prosecutorial and administrative entities in connection with the promotion of products for unapproved uses and other sales practices, including by the Department of Justice (DOJ), and various U.S.
Attorneys’ Offices, the HHS Office of Inspector General, the FDA, the Federal Trade Commission and various state Attorneys General offices.
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Any such fines, awards or other sanctions would have an adverse effect on our revenue, business, financial prospects, and reputation.
+Added: In the EU, the advertising and promotion of medicinal products are subject to both EU and EU Member States’ laws governing promotion of medicinal products, interactions with physicians and other healthcare professionals, misleading and comparative advertising and unfair commercial practices.
+Added: General requirements for advertising and promotion of medicinal products, such as direct-to-consumer advertising of prescription medicinal products, are established in EU law.
+Added: However, the details are governed by regulations in individual EU Member States and can differ from one country to another.
+Added: If the EU or an applicable EU Member State were to determine that we violated an applicable law or regulation, we could be subject to lawsuits, regulatory actions, penalties and other adverse consequences that would have an adverse effect on our revenue, business, financial prospects, and reputation.
Changes at the FDA and other government agencies could delay or prevent new products from being developed or commercialized in a timely manner or otherwise prevent those agencies from performing normal functions on which the operation of our business may rely, which could negatively impact our business.
−Removed: The ability of the FDA to review and approve new products can be affected by a variety of factors, including government budget and funding levels, ability to hire and retain key personnel and accept payment of user fees, and statutory, regulatory, and policy changes.
+Added: The ability of the FDA to review and approve new products can be affected by a variety of factors, including government budget and funding levels, ability to hire and retain key personnel and accept payment of user fees, layoffs and statutory, regulatory, and policy changes.
Average review times at the agency have fluctuated in recent years as a result.
−Removed: In addition, government funding of other government agencies on which our operations may rely, including those that fund research and development activities is subject to the political process, which is inherently fluid and unpredictable.
+Added: In addition, government funding of other government agencies on which our operations may rely, including those that fund research and development activities is subject to the political process, including executive and congressional priorities, the impacts of which are inherently fluid and unpredictable.
Disruptions at the FDA and other agencies may also slow the time necessary for new drugs to be reviewed and/or approved by necessary government agencies, which would adversely affect our business.
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government has shut down several times and certain regulatory agencies, such as the FDA, have had to furlough critical government employees and stop critical activities.
−Removed: If repeated or prolonged government shutdowns occur, it could significantly impact the ability of the FDA to timely review and process our regulatory submissions, and negatively impact other government operations on which we rely, which could have a material adverse effect on our business.
−Removed: We are subject to stringent regulation in connection with the marketing of NUPLAZID, DAYBUE and any other products derived from our product candidates, which could delay the development and commercialization of our products.
+Added: In addition, the current administration has enacted substantial reductions in force at various government agencies that, if applied in a material way, could significantly reduce the FDA’s and other agencies’ capacities to perform their functions in a manner consistent with past practices and could negatively impact our business.
+Added: If repeated or prolonged government shutdowns or material layoffs of agency personnel occur, it could significantly impact the ability of the FDA to timely review and process our regulatory submissions, and negatively impact other government operations on which we rely, which could have a material adverse effect on our business.
+Added: We are subject to stringent regulation in connection with the marketing of our products, which could delay the development and commercialization of our products.
The pharmaceutical industry is subject to stringent regulation by the FDA and other regulatory agencies in the U.S.
−Removed: and by comparable authorities in other countries.
−Removed: Neither we nor our collaborators can market a pharmaceutical product, including NUPLAZID and DAYBUE, in the U.S.
+Added: and by comparable foreign regulatory authorities in other jurisdictions.
+Added: Neither we nor our collaborators can market a pharmaceutical product in the U.S.
until it has completed rigorous preclinical testing and clinical trials and an extensive regulatory clearance process implemented by the FDA.
Satisfaction of regulatory requirements typically takes many years, depends upon the type, complexity and novelty of the product, and requires substantial resources.
−Removed: Even if regulatory approval is obtained, the FDA and other regulatory agencies may impose significant restrictions on the indicated uses, conditions for use, labeling, advertising, promotion, and/or marketing of such products, and requirements for post-approval studies, including additional research and development and clinical trials.
+Added: Even if regulatory approval is obtained, the FDA and comparable foreign regulatory authorities may impose significant restrictions on the indicated uses, conditions for use, labeling, advertising, promotion, and/or marketing of such products, and requirements for post-approval studies, including additional research and development and clinical trials.
These limitations may limit the size of the market for the product or result in the incurrence of additional costs.
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Accordingly, if we fail to comply with these regulations and restrictions, the commercialization of our product candidates, if approved, may be delayed or suspended, which may delay or impede our ability to generate product revenues.
−Removed: If our competitors develop and market products that are more effective than NUPLAZID, DAYBUE or our product candidates, if approved, they may reduce or eliminate our commercial opportunity.*
+Added: If our competitors develop and market products that are more effective than our products, they may reduce or eliminate our commercial opportunity.
Competition in the pharmaceutical and biotechnology industries is intense and expected to increase.
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In addition, Anavex has a product, Anavex 2-73, in development for the potential treatment of Rett syndrome and Taysha Gene Therapies and Neurogene are conducting Phase 1/2 clinical trials of gene therapies to treat Rett syndrome.
−Removed: Several academic institutions and pharmaceutical companies are currently conducting clinical trials for the treatment of various symptoms of Rett syndrome, including Unravel Bio and Vanderbilt University Medical Center, which are jointly conducting an early stage study with vorinostat (RVL-001).
+Added: Several academic institutions and pharmaceutical companies are
+Added: currently conducting clinical trials for the treatment of various symptoms of Rett syndrome, including Unravel Bio and Vanderbilt University Medical Center, which are jointly conducting an early stage study with vorinostat (RVL-001).
Other competitors may have a variety of drugs in development or awaiting approval from the FDA or comparable foreign regulatory authorities that could reach the market and become established before we have a product to sell for the applicable disorder.
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Our failure to compete effectively could have a material adverse effect on our business.
−Removed: If product liability lawsuits are brought against us, we may incur substantial liabilities and may be required to limit commercialization of NUPLAZID, DAYBUE or any other product for which we obtain regulatory approval, or development or commercialization of our product candidates, if approved.
−Removed: We face an inherent risk of product liability as a result of the commercial sales of NUPLAZID and DAYBUE in the U.S.
−Removed: and the clinical testing of our product candidates, and will face an even greater risk following commercial launch of DAYBUE in additional jurisdictions, if approved, or if we engage in the clinical testing of new product candidates or commercialize any additional products.
−Removed: For example, we may be sued if NUPLAZID, DAYBUE or any other product we develop allegedly causes injury or is found to be otherwise unsuitable for administration in humans.
+Added: If product liability lawsuits are brought against us, we may incur substantial liabilities and may be required to limit commercialization of our products, or development or commercialization of our product candidates, if approved.
+Added: We face an inherent risk of product liability as a result of the commercial sales of our products and the clinical testing of our product candidates.
+Added: For example, we may be sued if any of our products allegedly cause injury or are found to be otherwise unsuitable for administration in humans.
Any such product liability claims may include allegations of defects in manufacturing, defects in design, a failure to warn of dangers inherent in the product, negligence, strict liability or a breach of warranties.
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Regardless of the merits or eventual outcome, liability claims may result in:
−Removed: • decreased demand for our products or product candidates, if approved, that we may develop;
+Added: • decreased demand for our products or product candidates, if approved;
• injury to our reputation;
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• a decline in our stock price.
−Removed: Although we currently have product liability insurance that covers our clinical trials and the commercialization of NUPLAZID and DAYBUE, we may need to increase and expand this coverage, including if we commence larger scale trials and if our product candidates are approved for commercial sale.
+Added: Although we currently have product liability insurance that covers our clinical trials and the commercialization of our products, we may need to increase and expand this coverage, including if we commence larger scale trials and if our product candidates are approved for commercial sale.
This insurance may be prohibitively expensive or may not fully cover our potential liabilities.
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Extortion payments may alleviate the negative impact of a ransomware attack, but we may be unwilling or unable to make such payments (including, for example, if applicable laws or regulations prohibit such payments).
−Removed: Remote work has become more common and has increased risks to our information technology systems and data, as more of our employees work from home, utilizing network connections, computers and devices outside our premises, including at home, while in transit or in public locations.
+Added: Remote work has increased risks to our information technology systems and data, as our employees work from home, utilizing network connections, computers and devices outside our premises, including at home, while in transit or in public locations.
Future or past business transactions (such as acquisitions or integrations) could expose us to additional cybersecurity risks and vulnerabilities, as our systems could be negatively affected by vulnerabilities present in acquired or integrated entities’ systems and technologies.
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Vulnerabilities could be exploited and result in a security incident.
−Removed: Any of the previously identified or similar threats could cause a security incident or other interruption that could result in unauthorized, unlawful, or accidental acquisition, modification, destruction, loss, alteration, encryption, disclosure of, or access to our sensitive information or our information technology systems, or those of the third parties with whom we work.
+Added: Any of the previously identified or similar threats could cause, and in some cases have in the past caused, a security incident or other interruption that could result in unauthorized, unlawful, or accidental acquisition, modification, destruction, loss, alteration, encryption, disclosure of, or access to our sensitive information or our information technology systems, or those of the third parties with whom we work.
A security incident or other interruption could disrupt our ability (and that of third parties with whom we work) to provide our products.
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The market prices for securities of biotechnology companies in general, and drug discovery and development companies in particular, have been highly volatile and may continue to be highly volatile in the future.
−Removed: From the period between January 2, 2024 to October 31, 2024, the closing price of our common stock has ranged from a low of $14.29 per share to a high of $30.86 per share.
+Added: From the period between January 2, 2025 to April 30, 2025, the closing price of our common stock has ranged from a low of $14.10 per share to a high of $20.29 per share.
Furthermore, especially as we and our market capitalization have grown, the price of our common stock has been increasingly affected by quarterly and annual comparisons with the valuations and recommendations of the analysts who cover our business.
The following factors, in addition to other risk factors described in this section, may have a significant impact on the market price of our common stock:
−Removed: • the success of our commercialization of NUPLAZID in the U.S.
−Removed: for the treatment of hallucinations and delusions associated with PDP and DAYBUE in North AMerica for the treatment of Rett syndrome;
+Added: • the success of our commercialization of our products;
• the status and cost of development and commercialization of our products and product candidates, if approved, including compounds being developed under our collaborations;
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• the status and cost of development and commercialization of trofinetide for indications other than Rett syndrome and in jurisdictions outside North America;
−Removed: • any other communications or guidance from the FDA or other regulatory authorities that pertain to NUPLAZID, DAYBUE or our product candidates;
+Added: • any other communications or guidance from the FDA or other regulatory authorities that pertain to our products or product candidates;
• the status and cost of our PMRs for DAYBUE;
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In connection with our January 2016 public offering of common stock, we entered into a formal registration rights agreement with the Baker Entities to provide for these rights.
−Removed: Under the registration rights agreement, we have agreed that, if at any time and from time to time, the Baker Entities demand that we register their shares of our common stock for resale under the Securities Act, we would be obligated to effect such registration.
+Added: Under the registration rights agreement, we have agreed that, if at any time and from time to time, the Baker Entities demand that we register their shares of our common stock for resale under the Securities Act of 1933, as amended (the Securities Act), we would be obligated to effect such registration.
On May 25, 2022, we filed a registration statement covering the sale of up to 42,393,855 shares of our common stock, which includes 489,269 shares of our common stock issuable upon the exercise of warrants that were owned by the Baker Entities as of May 16, 2022, and which represented approximately 26 percent of our outstanding shares at the time.
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Although we believe these provisions collectively provide for an opportunity to receive higher bids by requiring potential acquirors to negotiate with our board of directors, they would apply even if the offer may be considered beneficial by some stockholders.
+Added: Our amended and restated bylaws provide that the Court of Chancery of the State of Delaware is the exclusive forum for certain disputes between us and our stockholders, which could limit our stockholders’ ability to obtain a favorable judicial forum for disputes with us or our directors, officers or employees.*
+Added: Our amended and restated bylaws provide that the Court of Chancery of the State of Delaware will be the sole and exclusive forum for (i) any derivative action or proceeding brought on our behalf, (ii) any action asserting a claim of breach of a fiduciary duty owed by any of our directors, officers or employees to our company or our stockholders, (iii) any action asserting a claim against our company or any director, officer or other employee arising pursuant to any provision of the General Corporation Law of the State of Delaware or our amended and restated certificate of incorporation or bylaws, (iv) any action to interpret, apply, enforce or determine the validity of our amended and restated certificate of incorporation or bylaws;
+Added: (v) any action as to which the General Corporation Law of the State of Delaware confers jurisdiction on the Court of Chancery of the State of Delaware;
+Added: and (vi) any action asserting a claim against our company governed by the internal affairs doctrine.
+Added: This choice of forum provision does not apply to suits brought to enforce a duty or liability created by the Securities Act.
+Added: This choice of forum provision may limit a stockholder’s ability to bring certain claims in a judicial forum that it finds favorable for disputes with us or any of our directors, officers, other employees or stockholders, which may discourage lawsuits with respect to such claims, although our stockholders will not be deemed to have waived our compliance with federal securities laws and the rules and regulations thereunder.
+Added: If a court were to find this choice of forum provision to be inapplicable or unenforceable in an action, we may incur additional costs associated with resolving such action in other jurisdictions, which could adversely affect our business and financial condition.
We do not intend to pay dividends on our common stock in the foreseeable future;
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There is no guarantee that our common stock will appreciate, and therefore, a holder of our common stock may not realize a return on his or her investment.
−Removed: General Risk Factors
−Removed: Our management has broad discretion over the use of our cash and we may not use our cash effectively, which could adversely affect our results of operations.
−Removed: Our management has significant flexibility in applying our cash resources and could use these resources for corporate purposes that do not increase our market value, or in ways with which our stockholders may not agree.
−Removed: We may use our cash resources for corporate purposes that do not yield a significant return or any return at all for our stockholders, which may cause our stock price to decline.
−Removed: We have incurred, and expect to continue to incur, significant costs as a result of laws and regulations relating to corporate governance and other matters.
−Removed: Laws and regulations affecting public companies, including provisions of the Dodd-Frank Wall Street Reform and Consumer Protection Act that was enacted in July 2010, the provisions of the Sarbanes-Oxley Act of 2002 (SOX), and rules adopted or proposed by the SEC and by The Nasdaq Stock Market, have resulted in, and will continue to result in, significant costs to us as we evaluate the implications of these rules and respond to their requirements.
−Removed: In the future, if we are not able to issue an evaluation of our internal control over financial reporting, as required, or we or our independent registered public accounting firm determine that our internal control over financial reporting is not effective, this shortcoming could have an adverse effect on our business and financial results and the price of our common stock could be negatively affected.
−Removed: New rules could make it more difficult or more costly for us to obtain certain types of insurance, including director and officer liability insurance, and we may be forced to accept reduced policy limits and coverage or incur substantially higher costs to obtain the coverage that is the same or similar to our current coverage.
−Removed: The impact of these events could also make it more difficult for us to attract and retain qualified persons to serve on our board of directors and board committees, and as our executive officers.
−Removed: We cannot predict or estimate the total amount of the costs we may incur or the timing of such costs to comply with these rules and regulations.
−Removed: Adverse securities and credit market conditions may significantly affect our ability to raise capital.
−Removed: Historically, turmoil and volatility in the financial markets (including recent volatility as a result of geopolitical and macroeconomic developments, as well as any related political or economic responses and counter-responses or otherwise by various global actors or the general effect on the global economy and supply chain) have adversely affected the market capitalizations of many biotechnology companies, and generally made equity and debt financing more difficult to obtain.
−Removed: These events, coupled with other factors, may limit our access to financing in the future.
−Removed: This could have a material adverse effect on our ability to access funding on acceptable terms, or at all, and our stock price may suffer further as a result.
OTHER INFORMATION
−Removed: Insider Trading Arrangements
−Removed: No officer or director, as defined in Rule 16a-1(f) under the Exchange Act, adopted or terminated a “Rule 10b5-1 trading arrangement” or a “non-Rule 10b5-1 trading arrangement,” as defined in Regulation S-K Item 408, during the fiscal quarter.
−Removed: Entry into a Material Definitive Agreement
−Removed: On November 5, 2024, we entered into an asset purchase agreement (the PRV Transfer Agreement), pursuant to which we agreed to sell a Rare Pediatric Disease PRV for $150.0 million, payable in cash, upon the closing of the sale.
−Removed: Pursuant to the Joint Venture and Licence Agreement, dated July 13, 2023, with Neuren, one third of the net proceeds from the sale of the PRV will be payable to Neuren.
−Removed: We were awarded the PRV under an FDA program intended to encourage the development of certain rare pediatric disease product applications.
−Removed: We received the PRV when DAYBUE was approved by the FDA in March 2023 for the treatment of Rett syndrome.
−Removed: The transactions contemplated by the PRV Transfer Agreement remain subject to customary closing conditions, including the expiration or termination of the required waiting period under the Hart-Scott-Rodino Antitrust Improvements Act of 1976.
−Removed: The PRV Transfer Agreement contains customary representations, warranties, covenants and indemnification provisions subject to certain limitations.
−Removed: The foregoing description of the PRV Transfer Agreement does not purport to be complete and is qualified in its entirety by the text of the PRV Transfer Agreement, a copy of which will be filed as an exhibit to our Annual Report on Form 10-K for the year ending December 31, 2024.
Amended and Restated Certificate of Incorporation, as amended (incorporated by reference to Exhibit 3.1 to the Registrant’s Quarterly Report on Form 10-Q, filed August 6, 2015).
Certificate of Amendment of Amended and Restated Certificate of Incorporation (incorporated by reference to Exhibit 3.2 to the Registrant’s Annual Report on Form 10-K, filed February 25, 2021).
−Removed: Amended and Restated Bylaws (incorporated by reference to Exhibit 3.1 to the Registrant’s Current Report on Form 8-K, filed September 12, 2013).
+Added: Amended and Restated Bylaws, effective through April 14, 2025 (incorporated by reference to Exhibit 3.1 to the Registrant’s Current Report on Form 8-K, filed September 12, 2013).
+Added: Amended and Restated Bylaws, effective on and after April 15, 2025 (incorporated by reference to Exhibit 3.1 to the Registrant’s Current Report on Form 8-K, filed April 16, 2025).
Form of common stock certificate of the Registrant (incorporated by reference to Exhibit 4.1 to Registration Statement No.
Form of Amended and Restated Warrant to Purchase Common Stock issued to purchasers in a private placement on December 17, 2012 (incorporated by reference to Exhibit 4.2 to the Registrant’s Annual Report on Form 10-K, filed on February 27, 2019).
−Removed: Executive Transition Agreement, dated September 23, 2024, by and between the Registrant and Stephen R.
−Removed: Davis (incorporated by reference to Exhibit 10.1 to the Registrant’s Current Report on Form 8-K, filed on September 23, 2024).
−Removed: Employment Agreement, dated September 23, 2024, by and between the Registrant and Catherine Owen Adams (incorporated by reference to Exhibit 10.2 to the Registrant’s Current Report on Form 8-K, filed on September 23, 2024).
−Removed: Acadia Pharmaceuticals Inc.
−Removed: 2024 Inducement Plan (incorporated by reference to Exhibit 99.1 to Registration Statement No.
−Removed: Forms of Standard Stock Option Grant Notice and Stock Option Agreement under the Acadia Pharmaceuticals Inc.
−Removed: 2024 Inducement Plan (incorporated by reference to Exhibit 99.2 to Registration Statement No.
−Removed: Forms of Standard Restricted Stock Unit Grant Notice and Restricted Stock Unit Agreement under the Acadia Pharmaceuticals Inc.
−Removed: 2024 Inducement Plan (incorporated by reference to Exhibit 99.3 to Registration Statement No.
−Removed: Forms of Standard Performance Stock Unit Grant Notice and Performance Stock Unit Agreement under the Acadia Pharmaceuticals Inc.
−Removed: 2024 Inducement Plan.
+Added: Non-Employee Director Compensation Policy, effective April 14, 2025.
Certification of Catherine Owen Adams, Chief Executive Officer, pursuant to Rule 13a-14(a) or Rule 15d-14(a) of the Securities Exchange Act of 1934, as adopted pursuant to Section 302 of the Sarbanes-Oxley Act of 2002.
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Section 1350, as adopted pursuant to Section 906 of the Sarbanes-Oxley Act of 2002.
−Removed: The following financial statements from the Registrant’s Quarterly Report on Form 10-Q for the quarter ended September 30, 2024, filed on November 6, 2024, formatted in iXBRL (Inline Extensible Business Reporting Language), are filed herewith:
−Removed: (i) Condensed Consolidated Balance Sheets, (ii) Condensed Consolidated Statements of Operations, (iii) Condensed Consolidated Statements of Comprehensive Income (Loss), (iv) Condensed Consolidated Statements of Cash Flows, (v) Condensed Consolidated Statements of Stockholders’ Equity and (vi) Notes to Condensed Consolidated Financial Statements.
+Added: The following financial statements from the Registrant’s Quarterly Report on Form 10-Q for the quarter ended March 31, 2025, filed on May 7, 2025, formatted in iXBRL (Inline Extensible Business Reporting Language), are filed herewith:
+Added: (i) Condensed Consolidated Balance Sheets, (ii) Condensed Consolidated Statements of Operations, (iii) Condensed Consolidated Statements of Comprehensive Income, (iv) Condensed Consolidated Statements of Cash Flows, (v) Condensed Consolidated Statements of Stockholders’ Equity and (vi) Notes to Condensed Consolidated Financial Statements.
Cover Page Interactive Data File (formatted as inline XBRL and contained in Exhibit 101)
_________________
−Removed: a Indicates management contract or compensatory plan or arrangement.
−Removed: b The information in Exhibits 32.1 and 32.2 shall not be deemed “filed” for purposes of Section 18 of the Exchange Act, or otherwise subject to the liabilities of that section, nor shall it be deemed incorporated by reference in any filing under the Securities Act or the Exchange Act (including this Annual Report), unless the Registrant specifically incorporates the foregoing information into those documents by reference.
+Added: a The information in Exhibits 32.1 and 32.2 shall not be deemed “filed” for purposes of Section 18 of the Exchange Act, or otherwise subject to the liabilities of that section, nor shall it be deemed incorporated by reference in any filing under the Securities Act or the Exchange Act (including this report), unless the Registrant specifically incorporates the foregoing information into those documents by reference.
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned thereunto duly authorized.
Acadia Pharmaceuticals Inc.
−Removed: November 6, 2024
Executive Vice President and Chief Financial Officer
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Compared sentence by sentence after normalising whitespace, quotation marks, case and digits, so re-formatting and restated figures do not read as changed language. Wording changes appear as one removal and one addition. The current filing and the prior one are authoritative.