CAPR

Summary Risk Factors Our business is subject to a number of risks, including risks that may prevent us from achieving our business objectives or adversely affect our business, financial condition, results of operations and prospects.
These risks include those related to the development, regulatory approval and potential commercialization of our product candidates, our manufacturing activities, intellectual property, third-party relationships, competitive factors, product and environmental liability, and our common stock.
These risks are discussed more fully below and include, but are not limited to, risks related to: Risks Related to Our Business ● substantial additional funding may be required to complete the development and potential commercialization of our product candidates in the United States and internationally; ● the Company has incurred significant losses and may never achieve or sustain profitability; ● the occurrence of security breaches, improper access to or disclosure of our data or third-party data, and other cyber incidents or undesirable cyber activity related to our systems or those of our third-party vendors; and ● we may not have adequate personnel and may not be able to attract or retain personnel necessary to develop and potentially commercialize our product candidates. Risks Related to Clinical and Commercialization Activities ● our success depends upon the viability of our product candidates, which require regulatory approval prior to commercialization, and we cannot be certain that any of them will receive such approval; ● delays in the commencement, enrollment or completion of clinical testing could result in increased costs to us and may delay or limit our ability to obtain regulatory approval for our product candidates; ● we may not be able to manufacture Deramiocel in sufficient quantities or at acceptable cost to meet market demand; ● product candidates can fail to meet safety or efficacy endpoints at any time during the clinical development process, which would likely prevent them from becoming commercial products; ● we may not be able to satisfy clinical or regulatory requirements necessary for the approval of our product candidates in the U.S., Europe, Japan or other select territories; ● we may not be able to reach the milestones set forth in our distribution agreements and therefore may not receive the financial benefits associated with those agreements; ● our exosome technologies may not demonstrate sufficient biological activity or scalability in development; ● our partners may not perform as expected and therefore we may not realize the anticipated benefits of those agreements; and ● the successful commercialization of our product candidates will depend in part on the extent to which governmental authorities and health insurers establish coverage, adequate reimbursement levels and pricing policies, including potential most-favored-nation pricing pilots or proposals that could require additional rebates for our product candidates, if approved. Risks Related to the Manufacturing of our Product Candidates ● the manufacturing of our product candidates is dependent on complex supply chains, including the availability of donor hearts and other raw materials that are critical for the manufacturing of our product candidates; ● we may need to rely upon third-party manufacturers to expand our manufacturing capabilities for later-stage clinical trials and potential commercialization; ● we may not have sufficient manufacturing capacity or facilities required for any future scale-up of manufacturing; ● we may not be able to successfully replicate or scale our manufacturing processes; ● we may not be able to comply with current Good Manufacturing Practice (“cGMP”) regulations; ● we may not be able to identify or retain necessary manufacturing personnel; and ● the FDA may not ultimately determine that our manufacturing processes are comparable or acceptable, or approve our manufacturing facilities for commercial production. Risks Related to Our Intellectual Property ● we may not be able to obtain, maintain, protect, and enforce our intellectual property rights; ● we may face potential challenges to the validity, enforceability, or scope of our intellectual property; ● we may experience claims from third parties that we are infringing their patents or other intellectual property rights; and ● we may not be able to satisfy our obligations under our licensing agreements.
Risks Related to Our Relationships with Third Parties ● we depend on our relationships with our licensors, collaborators, and other third parties and these relationships may not continue or may not be successful; and ● we will depend on the ability of Nippon Shinyaku to perform according to the terms of the U.S.
Distribution and Japan Distribution Agreements and all applicable laws, and to successfully commercialize Deramiocel for the treatment of DMD.
Risks Related to Competitive Factors ● our products, if approved, will likely face significant competition; and ● any of our product candidates for which we receive regulatory approval may not achieve broad market acceptance, which could limit the revenue we may generate from their sales, if any.
Risks Related to Product and Environmental Liability ● our products or product candidates may expose us to potential product liability.
Risks Related to Our Business We need additional funding before we can complete the development of our product candidates.
As of December 31, 2025, we had cash, cash equivalents, and marketable securities totaling approximately $318.1 million.
Factors relating to our business that may contribute to these fluctuations include the following factors: ● our need for additional capital to fund our trials and development programs; ● delays in the commencement, enrollment, and timing of clinical testing; ● the viability of Deramiocel as a potential product candidate and its development through all stages of clinical development; ● the viability of our exosome technologies as potential product candidates and the advancement of our exosome technologies through all stages of their preclinical and clinical development; ● any delays in regulatory review and approval of our product candidates in clinical development; ● our ability to receive regulatory approval or commercialize our product candidates, within and outside the United States; ● potential side effects of our current or future products and product candidates that could delay or prevent commercialization or cause an approved treatment to be taken off the market; ● market acceptance of our product candidates; ● our ability to establish an effective sales and marketing infrastructure once our products are commercialized, as necessary or to establish partnerships with other companies who have greater sales and marketing capabilities; ● the ability of our distribution partner, Nippon Shinyaku, to successfully market and sell our Deramiocel product if and to the extent it is approved; ● our ability to establish or maintain collaborations, licensing or other arrangements, including strategic partnerships for Deramiocel outside of DMD and our exosome technologies; ● our ability and third parties’ abilities to obtain and protect intellectual property rights; ● competition from existing products or new products that may emerge; ● guidelines and recommendations of therapies published by various organizations; ● the ability of patients to obtain coverage of, or sufficient reimbursement for, our product candidates; ● our ability to maintain adequate insurance policies; ● our ability to successfully manufacture our product candidates in sufficient quantities and on a timely basis to meet clinical trial and potential commercial demand; ● our dependency on third parties to formulate and manufacture our product candidates, as necessary; ● our ability to maintain and staff our current manufacturing facilities; ● our ability to build or secure new manufacturing facilities, if necessary, and achieve and maintain cGMP and obtain required certifications as required; ● costs related to and outcomes of potential intellectual property litigation; ● compliance with obligations under intellectual property licenses with third parties; ● our ability to implement additional internal systems and infrastructure; ● our ability to adequately support future growth; ● if our products are approved for commercial sale, the ability to secure adequate reimbursement levels for our products; ● our ability to attract and retain key personnel to manage our business effectively; and ● the ability of members of our senior management to manage our business and operations.
Additionally, we cannot predict with any certainty if, or when, we might commence any additional clinical trials of our exosome product candidates, whether we will be able to secure additional strategic partners, or whether our current trials will yield sufficient data to permit us to proceed with additional clinical development and ultimately submit an application for regulatory approval of our exosome product candidates in the United States or abroad, or whether such applications will be accepted by the appropriate regulatory agencies.
The success of our product candidates will depend on several factors, including the following: ● our ability to demonstrate our products’ safety, tolerability and efficacy to the FDA or any comparable foreign regulatory authority for marketing approval; ● successful and timely completion of our clinical trials; ● initiation and successful patient enrollment and completion of additional clinical trials on a timely basis; ● timely receipt of marketing approval for our products; ● obtaining and maintaining patent protection, trade secret protection and regulatory exclusivity, both in the United States and internationally; ● avoiding and successfully defending against any claims that we have infringed, misappropriated or otherwise violated any intellectual property of any third-party; ● the performance of our current and future distributors or collaborators, if any; ● the extent of, and our ability to timely complete, any required post-marketing approval commitments imposed by FDA or other applicable regulatory authorities; ● successfully developing a companion diagnostic test on a timely and cost effective basis, if required; ● establishment of supply arrangements with third-parties for raw materials and product supplies and potential manufacturers who are able to manufacture clinical trial and commercial quantities of drug substance and drug products; ● our ability to develop, validate and maintain a commercially viable manufacturing process that is compliant with cGMP at a scale sufficient to meet anticipated demand; ● successful launch of commercial sales following marketing approval; ● a continued acceptable safety profile following marketing approval; ● commercial acceptance by patients, the medical community and third-party payors; ● the availability of coverage and adequate reimbursement and pricing by third-party payors and government authorities; ● the availability, perceived advantages, relative cost, relative safety and relative efficacy of alternative and competing treatments; ● the impact of infectious disease outbreaks or pandemics on our operations, ability to conduct clinical trials and on the ability of our regulators to review and approve or authorize our products; ● our ability to compete with other therapies; and ● our ability to conduct post-marketing surveillance and comply with requirements of FDA and other comparable regulatory authorities after product approval.
Our corporate headquarters and our manufacturing and research facilities are located in San Diego and in the Los Angeles, California area, a region known for seismic activity, as well as being susceptible to drought and fires.
In addition, outbreaks of viruses, infectious diseases or pandemics (including, for example, the outbreak of the novel coronavirus (COVID-19)), terrorist acts or acts of war targeted at the United States, and specifically in the California region, or geopolitical conflicts, such as the Russia-Ukraine conflict, Venezuela, and the conflicts in Gaza, Iran, and across the Middle East, could cause damage or disruption to us, our employees, facilities, contractors and collaborators, which could have a material adverse effect on our business, financial condition and results of operations.
Tariffs imposed by foreign governments in retaliation for U.S. trade measures could adversely affect our international sales, results of operations, and financial condition.
In response to tariffs and other trade measures imposed by the United States, certain foreign governments have implemented, and may in the future implement, retaliatory tariffs or other trade restrictions on products imported from the United States.
To the extent such measures apply to our products, they may increase the cost of our products to customers in affected markets, reduce demand for our products, and make our products less competitive relative to locally sourced or other non-U.S. products.
Retaliatory tariffs and related trade actions could also disrupt our supply chains, require us to modify pricing, sourcing, or distribution strategies, or result in the loss of customers or market share in impacted jurisdictions.
In addition, uncertainty regarding the scope, duration, and potential escalation of trade disputes may negatively affect customer purchasing decisions and our ability to forecast demand.
Any of these factors could adversely affect our revenues, margins, cash flows, and overall financial condition.
The ultimate impact of retaliatory tariffs and related trade measures will depend on various factors, including the magnitude and duration of the tariffs on our products, and broader macroeconomic conditions.
To manage this growth, we will need to expand our facilities, augment our operational, financial and management systems and hire and train additional qualified personnel, including people and companies with expertise in commercialization activities, some of whom may be outside consultants who are not our full-time employees.
In order to obtain FDA approval of Deramiocel for the treatment of DMD, we submitted to the FDA a BLA for potential approval of Deramiocel, which currently is under review.
In addition, for biologic and cell therapy products, regulatory review may include scrutiny of our CMC package, manufacturing controls and facility readiness, and may require process changes, comparability data, or other remediation that could delay approval or limit the scope of an approved indication.
In addition, because we have only conducted preclinical studies and, in collaboration with NIAID, recently initiated a Phase 1 clinical study, with our exosome technologies, we have not yet been able to assess their safety in humans, and there may be short-term or long-term effects from treatment with our exosomes that we cannot predict at this time.
We hope to file additional INDs over the next several years, including with respect to our exosome technologies in one or more indications as well as potentially in BMD.
The commencement, enrollment and completion of clinical trials can be delayed for a number of reasons, including, but not limited to, delays related to: ● findings in preclinical studies; ● reaching agreements on acceptable terms with prospective CROs, vendors and trial sites, the terms of which can be subject to extensive negotiation and may vary significantly among different CROs, vendors and trial sites; ● obtaining regulatory clearance to commence a clinical trial; ● complying with conditions imposed by a regulatory authority regarding the scope or term of a clinical trial, or being required to conduct additional trials before moving on to the next phase of trials; ● obtaining IRB approval to conduct a clinical trial at numerous prospective sites; ● recruiting and enrolling patients to participate in clinical trials for a variety of reasons, including the size of the patient population, nature of trial protocol, meeting the enrollment criteria for our studies, screening failures, the inability of the sites to conduct trial procedures properly, the inability of the sites to devote their resources to the trial, the availability of approved effective treatments for the relevant disease and competition from other clinical trial programs for similar indications; ● the impact of infectious disease outbreaks or pandemics on site personnel availability, patient screening and patient enrollment; ● competition from other companies operating in the same disease setting; ● developing and validating any companion diagnostic to be used in the trial, to the extent we are required to do so; ● patients failing to comply with the clinical trial protocol or dropping out of a trial; ● clinical trial sites failing to comply with the clinical trial protocol or dropping out of a trial; ● addressing any conflicts with new or existing laws or regulations; ● the need to add new clinical trial sites; ● retaining patients who have initiated their participation in a clinical trial but may withdraw due to the treatment protocol, lack of efficacy, personal issues, or side effects from the therapy, or who are lost to further follow-up; ● manufacturing sufficient quantities of a product candidate for use in clinical trials on a timely basis; ● obtaining advice from regulatory authorities regarding the statistical analysis plan to be used to evaluate the clinical trial data or other trial design issues; ● demonstrating the bioequivalence of products we manufacture to prior products manufactured by us; ● complying with design protocols of any applicable special protocol assessment we receive from the FDA; ● severe or unexpected drug-related side effects experienced by patients in a clinical trial; ● collecting, analyzing and reporting final data from the clinical trials; ● breaches in quality of manufacturing runs that compromise all or some of the doses made; positive results in FDA-required viral testing; karyotypic abnormalities in our cell product; or contamination in our manufacturing facilities, as well as equipment failures, operator error, variability in yields or cell viability, or other deviations that may result in lot failures or product loss, all of which events would necessitate disposal of all cells made from that source; ● availability of materials provided by third parties necessary to manufacture our product candidates; ● availability of adequate amounts of acceptable tissue for preparation of master cell banks for our products; ● requirements to conduct additional trials and studies, and increased expenses associated with the services of the Company’s CROs and other third parties; and ● meeting logistical requirements for the delivery of investigational product.
Supreme Court issued an opinion holding that courts reviewing agency action pursuant to the Administrative Procedure Act (APA) “must exercise their independent judgment” and “may not defer to an agency interpretation of the law simply because a statute is ambiguous.” The decision may have a significant impact on how lower courts evaluate challenges to agency interpretations of law, including those by the U.S.
In addition, federal agency activities, priorities, leadership, policies, rulemaking, communications, spending, and staffing may be significantly impacted by election cycles and legislative developments.
For example, the current presidential administration has signaled its continued commitment to significantly reduce government spending through cuts to federal healthcare programs and reductions in the workforces of key government agencies, such as the U.S.
Efforts by the current administration to further limit federal agency budgets or personnel may result in reductions to agency budgets, employees, and operations.
The administration and agencies have also made abrupt announcements about new or changed regulatory policies, such as policies related to use of AI to review product applications.
And, federal government shutdowns may prevent the FDA or other regulatory authorities from conducting their regular inspections, reviews or other regulatory activities, and may significantly impact the ability of the FDA to timely review and process our regulatory submissions.
These developments may lead to slower response times and longer review periods, potentially affecting our ability to progress development of our product candidates or obtain regulatory approval for our product candidates.
In addition, changes in the administration’s policies and personnel could result in decisions that differ from, or supersede, those made by government personnel under prior administrations.
There are also a number of healthcare-related legislative and regulatory initiatives and reforms in the United States that significantly affect the biopharmaceutical industry.
For example, there has been heightened governmental scrutiny in the U.S. of pharmaceutical pricing practices in light of the rising cost of prescription drugs and biologics.
Such scrutiny has resulted in several congressional inquiries and proposed and enacted federal and state legislation designed to, among other things, bring more transparency to product pricing, review the relationship between pricing and manufacturer patient programs, and reform government program reimbursement methodologies for products.
Also, changes in the administration’s policies and personnel may result in decisions contrary to or overriding decisions previously made by government personnel under prior administrations.
The degree of market acceptance of our product candidates, if approved for commercial sale, will depend on a number of factors, including: ● the efficacy and safety of the product; ● the potential advantages of the product compared to alternative therapies; ● the prevalence and severity of any side effects; ● whether the product is designated under physician and other provider treatment guidelines as a first-, second- or third-line therapy; ● our ability, or the ability of any future collaborators, to offer the product for sale at competitive prices; ● the product’s convenience and ease of administration for patients and healthcare practitioners compared to alternative treatments; ● site-of-care requirements, infusion logistics, and the ability of treatment centers and payors to support administration and access on a timely basis; ● the willingness of the target patient population to try, and of physicians to prescribe, the product; ● limitations or warnings, including distribution or use restrictions and safety information contained in the product’s approved labeling; ● the strength of sales, marketing and distribution support; ● the performance of third-party distributors, such as our exclusive distributor for our lead product candidate, Deramiocel; ● changes in the standard of care for the targeted indications for the product; and ● the availability of coverage by, and the amount of reimbursement from, government payors, managed care plans and other third-party payors.

and 105 more.

Gone since FY2024

Summary Risk Factors Our business is subject to a number of risks, including risks that may prevent us from achieving our business objectives or may adversely affect our business, clinical and commercialization activities, the manufacturing of our product candidates, intellectual property, third-party relationships, competition factors, product and environmental liability, and common stock.
These risks are discussed more fully below and include, but are not limited to, risks related to: Risks Related to Our Business ● substantial additional funding is needed to complete the development and commercialization of our product candidates within and outside the United States; ● the Company has incurred significant losses and may never be profitable; ● the occurrence of security breaches, improper access to or disclosure of our data or user data, and other cyber incidents or undesirable cyber activity related to our, or our third-party vendor’s systems and data; and ● we may not have adequate personnel and may not be able to attract or retain personnel needed to develop our products. Risks Related to Clinical and Commercialization Activities ● our success depends upon the viability of our product candidates, all of which require regulatory approval to commercialize and we cannot be certain any of them will receive regulatory approval to be commercialized; ● delays in commencement, enrollment, and completion of clinical testing could result in increased costs to us and delay or limit our ability to obtain regulatory approval for our product candidates; ● we may not be able to manufacture deramiocel in sufficient quantities to meet market demand; ● product candidates can fail to meet their efficacy endpoints at any time during the clinical development process, which would likely make them ineligible for becoming commercial products; ● we may not be able to satisfy clinical and/or regulatory requirements necessary for the approval of our product in the U.S., Europe, Japan or other select territories; ● we may not be able to reach the milestones set forth in our distribution agreements therefore preventing us from receiving the financial benefits of those agreements; ● our exosome technologies are unproven in their ability to achieve sufficient biological activity or scale in development to date; and ● our partners may not perform as expected and therefore deny us the financial benefits of those agreements.
Risks Related to the Manufacturing of our Product Candidates ● the manufacturing of our product candidates is heavily reliant on supply chain requirements including the availability of donor hearts and other raw materials that are critical for the manufacturing of our product candidates; ● we may need to rely upon third-party manufacturers for the expansion of our manufacturing capabilities for later-stage clinical trials and for ultimate commercialization; ● we may not have adequate manufacturing facilities required for any scale-up of manufacturing which may be required in the future; ● we may not be able to replicate our manufacturing processes; ● we may not be able to comply with cGMP regulations; ● we may not be able to identify or retain necessary manufacturing personnel; ● the FDA may not accept the viability or comparability of our manufacturing processes; and ● the FDA may not approve our manufacturing facilities for the manufacture of commercial products .
Risks Related to Our Intellectual Property ● we may not be able to obtain, maintain, protect, and enforce our intellectual property rights; ● we may face potential challenges to the validity, enforceability, or scope of our intellectual property; ● we may experience claims from third parties that we are infringing their patents or other intellectual property rights; and ● we may not be able to satisfy our obligations under our licensing agreements.
Risks Related to Our Relationships with Third Parties ● we depend on our relationships with our licensors, collaborators, and other third parties and there is no guarantee that such relationships will continue; and ● we will depend on the ability of Nippon Shinyaku to perform according to the terms of the U.S.
Distribution and Japan Distribution Agreements and all applicable laws, and to successfully commercialize our lead product deramiocel in DMD.
Risks Related to Competitive Factors ● our products, if approved, will likely face intense competition; and ● any of our product candidates for which we receive regulatory approval may not achieve broad market acceptance, which could limit the revenue that we will generate from their sales, if any.
Risks Related to Product and Environmental Liability ● our products may expose us to potential product liability.
Risks Related to Our Business We need substantial additional funding before we can complete the development of our product candidates.
As of December 31, 2024, we had cash, cash equivalents, and marketable securities totaling approximately $151.5 million.
Additionally, we received a milestone payment of $10.0 million in the first quarter of 2025 under the terms of our U.S.
Distribution Agreement with Nippon Shinyaku and we may potentially receive other additional development and sales-based milestones.
Factors relating to our business that may contribute to these fluctuations include the following factors: ● our need for substantial additional capital to fund our trials and development programs; ● delays in the commencement, enrollment, and timing of clinical testing; ● the viability of deramiocel as a potential product candidate and its development through all stages of clinical development; ● the viability of our exosome technologies as potential product candidates and the advancement of our exosome technologies through all stages of its preclinical and clinical development; ● any delays in regulatory review and approval of our product candidates in clinical development; ● our ability to receive regulatory approval or commercialize our product candidates, within and outside the United States; ● potential side effects of our current or future products and product candidates that could delay or prevent commercialization or cause an approved treatment to be taken off the market; ● market acceptance of our product candidates; ● our ability to establish an effective sales and marketing infrastructure once our products are commercialized, as necessary or to establish partnerships with other companies who have greater sales and marketing capabilities; ● the ability of our distribution partner, Nippon Shinyaku, to successfully market and sell our deramiocel product if and to the extent it is approved; ● our ability to establish or maintain collaborations, licensing or other arrangements, including strategic partnerships for deramiocel outside of DMD and our exosome technologies; ● our ability and third parties’ abilities to obtain and protect intellectual property rights; ● competition from existing products or new products that may emerge; ● guidelines and recommendations of therapies published by various organizations; ● the ability of patients to obtain coverage of, or sufficient reimbursement for, our product candidates; ● our ability to maintain adequate insurance policies; ● our ability to successfully manufacture our product candidates in sufficient quantities and on a timely basis to meet clinical trial and potential commercial demand; ● our dependency on third parties to formulate and manufacture our product candidates, as necessary; ● our ability to maintain and staff our current manufacturing facilities; ● our ability to build or secure new manufacturing facilities, if necessary, and achieve and maintain cGMP and obtain required certifications as required; ● costs related to and outcomes of potential intellectual property litigation; ● compliance with obligations under intellectual property licenses with third parties; ● our ability to implement additional internal systems and infrastructure; ● our ability to adequately support future growth; ● if our products are approved for commercial sale, the ability to secure adequate reimbursement levels for our products; ● our ability to attract and retain key personnel to manage our business effectively; and ● the ability of members of our senior management to manage our business and operations.
We cannot predict with any certainty the results of such clinical testing, including the results of our ongoing Phase 3 trial of our deramiocel product candidate for DMD.
Additionally, we cannot predict with any certainty if, or when, we might commence any clinical trials of our exosome product candidates, whether we will be able to secure additional strategic partners, or whether our current trials will yield sufficient data to permit us to proceed with additional clinical development and ultimately submit an application for regulatory approval of our exosome product candidates in the United States or abroad, or whether such applications will be accepted by the appropriate regulatory agencies.
The success of our product candidates will depend on several factors, including the following: ● our ability to demonstrate our products’ safety, tolerability and efficacy to the FDA or any comparable foreign regulatory authority for marketing approval; ● successful and timely completion of our clinical trials; ● initiation and successful patient enrollment and completion of additional clinical trials on a timely basis; ● timely receipt of marketing approval for our products; ● obtaining and maintaining patent protection, trade secret protection and regulatory exclusivity, both in the United States and internationally; ● avoiding and successfully defending against any claims that we have infringed, misappropriated or otherwise violated any intellectual property of any third-party; ● the performance of our current and future distributors or collaborators, if any; ● the extent of, and our ability to timely complete, any required post-marketing approval commitments imposed by FDA or other applicable regulatory authorities; ● successfully developing a companion diagnostic test on a timely and cost effective basis, if required; ● establishment of supply arrangements with third-parties for raw materials and product supplies and potential manufacturers who are able to manufacture clinical trial and commercial quantities of drug substance and drug products; ● our ability to develop, validate and maintain a commercially viable manufacturing process that is compliant with cGMP at a scale sufficient to meet anticipated demand; ● establishment of arrangements with potential manufacturers who are able to develop, validate and maintain a commercially viable manufacturing process that is compliant with cGMP at a scale sufficient to meet anticipated demand and over time enable us to reduce our cost of manufacturing, if necessary; ● successful launch of commercial sales following marketing approval; ● a continued acceptable safety profile following marketing approval; ● commercial acceptance by patients, the medical community and third-party payors; ● the availability of coverage and adequate reimbursement and pricing by third-party payors and government authorities; ● the availability, perceived advantages, relative cost, relative safety and relative efficacy of alternative and competing treatments; ● the impact of infectious disease outbreaks or pandemics on our operations, ability to conduct clinical trials and on the ability of our regulators to review and approve or authorize our products; ● our ability to compete with other therapies; and ● our ability to conduct post-marketing surveillance and comply with requirements of FDA and other comparable regulatory authorities after product approval.
Our corporate headquarters and our manufacturing and research facilities are located in San Diego and in the greater Los Angeles, California area, a region known for seismic activity, as well as being susceptible to drought and fires.
In addition, outbreaks of viruses, infectious diseases or pandemics (including, for example, the outbreak of the novel coronavirus (COVID-19)), terrorist acts or acts of war targeted at the United States, and specifically in the California region, or geopolitical conflicts, such as the Russia-Ukraine conflict and the conflicts in the Middle East, could cause damage or disruption to us, our employees, facilities, contractors and collaborators, which could have a material adverse effect on our business, financial condition and results of operations.
To manage this growth, we may need to expand our facilities, augment our operational, financial and management systems and hire and train additional qualified personnel.
In order to obtain FDA approval of any of our product candidates, we submitted to the FDA a BLA for potential approval of deramiocel, which BLA has been accepted by the FDA for review.
In addition, because we have only conducted preclinical studies with our exosome technologies, we have not yet been able to assess their safety in humans, and there may be short-term or long-term effects from treatment with our exosomes that we cannot predict at this time.
We hope to file additional INDs over the next several years, including with respect to our exosome technologies in one or more indications.
The commencement, enrollment and completion of clinical trials can be delayed for a number of reasons, including, but not limited to, delays related to: ● findings in preclinical studies; ● reaching agreements on acceptable terms with prospective CROs, vendors and trial sites, the terms of which can be subject to extensive negotiation and may vary significantly among different CROs, vendors and trial sites; ● obtaining regulatory clearance to commence a clinical trial; ● complying with conditions imposed by a regulatory authority regarding the scope or term of a clinical trial, or being required to conduct additional trials before moving on to the next phase of trials; ● obtaining IRB approval to conduct a clinical trial at numerous prospective sites; ● recruiting and enrolling patients to participate in clinical trials for a variety of reasons, including the size of the patient population, nature of trial protocol, meeting the enrollment criteria for our studies, screening failures, the inability of the sites to conduct trial procedures properly, the inability of the sites to devote their resources to the trial, the availability of approved effective treatments for the relevant disease and competition from other clinical trial programs for similar indications; ● the impact of infectious disease outbreaks or pandemics on site personnel availability, patient screening and patient enrollment; ● competition from other companies operating in the same disease setting; ● developing and validating any companion diagnostic to be used in the trial, to the extent we are required to do so; ● patients failing to comply with the clinical trial protocol or dropping out of a trial; ● clinical trial sites failing to comply with the clinical trial protocol or dropping out of a trial; ● addressing any conflicts with new or existing laws or regulations; ● the need to add new clinical trial sites; ● retaining patients who have initiated their participation in a clinical trial but may withdraw due to the treatment protocol, lack of efficacy, personal issues, or side effects from the therapy, or who are lost to further follow-up; ● manufacturing sufficient quantities of a product candidate for use in clinical trials on a timely basis; ● obtaining advice from regulatory authorities regarding the statistical analysis plan to be used to evaluate the clinical trial data or other trial design issues; ● demonstrating the bioequivalence of products we manufacture to prior products manufactured by us; ● complying with design protocols of any applicable special protocol assessment we receive from the FDA; ● severe or unexpected drug-related side effects experienced by patients in a clinical trial; ● collecting, analyzing and reporting final data from the clinical trials; ● breaches in quality of manufacturing runs that compromise all or some of the doses made; positive results in FDA-required viral testing; karyotypic abnormalities in our cell product; or contamination in our manufacturing facilities, all of which events would necessitate disposal of all cells made from that source; ● availability of materials provided by third parties necessary to manufacture our product candidates; ● availability of adequate amounts of acceptable tissue for preparation of master cell banks for our products; ● requirements to conduct additional trials and studies, and increased expenses associated with the services of the Company’s CROs and other third parties; and ● meeting logistical requirements for the delivery of investigational product.
Supreme Court issued an opinion holding that courts reviewing agency action pursuant to the Administrative Procedure Act (APA) “must exercise their independent judgment” and “may not defer to an agency interpretation of the law simply because a statute is ambiguous.” The decision will have a significant impact on how lower courts evaluate challenges to agency interpretations of law, including those by U.S.
In addition, federal agency priorities, leadership, policies, rulemaking, communications, spending, and staffing may be significantly impacted by election cycles.
For example, the current presidential administration’s commitment to significantly reduce government spending through cuts to federal healthcare programs and reductions in the workforces of key government agencies, such as the U.S.
Efforts by the current administration to limit federal agency budgets or personnel may result in reductions to agency budgets, employees, and operations, which may lead to slower response times and longer review periods, potentially affecting our ability to progress development of our product candidates or obtain regulatory approval for our product candidates.
The degree of market acceptance of our product candidates, if approved for commercial sale, will depend on a number of factors, including: ● the efficacy and safety of the product; ● the potential advantages of the product compared to alternative therapies; ● the prevalence and severity of any side effects; ● whether the product is designated under physician and other provider treatment guidelines as a first-, second- or third-line therapy; ● our ability, or the ability of any future collaborators, to offer the product for sale at competitive prices; ● the product’s convenience and ease of administration for patients and healthcare practitioners compared to alternative treatments; ● the willingness of the target patient population to try, and of physicians to prescribe, the product; ● limitations or warnings, including distribution or use restrictions and safety information contained in the product’s approved labeling; ● the strength of sales, marketing and distribution support; ● the performance of third-party distributors, such as our exclusive distributor for our lead product candidate, deramiocel; ● changes in the standard of care for the targeted indications for the product; and ● the availability of coverage by, and the amount of reimbursement from, government payors, managed care plans and other third-party payors.
There are many pharmaceutical companies, biotechnology companies, public and private universities, government agencies and research organizations that compete with us in developing various approaches to the treatment of DMD which includes competitors both in the United States and internationally.
With deramiocel, we expect to face competition from existing products and products in development.
At this time, there are four FDA conditionally approved exon skipping drugs: EXONDYS 51 (eteplirsen), AMONDYS 45 (casimersen) and VYONDYS 53 (golodirsen), which are PMOs approved for the treatment of DMD patients amenable to Exon 51, Exon 45 and Exon 53 skipping, respectively, and are marketed by Sarepta Therapeutics, Inc., and VILTEPSO (vitolarsen), a PMO approved for the treatment of DMD patients amenable to Exon 53 skipping, which is marketed by Nippon Shinyaku through its U.S. subsidiary, NS Pharma, Inc.
Currently, Sarepta’s microdystrophin gene therapy, Elevidys (delandistrogene moxeparvovec) is approved for the treatment of ambulant individuals with Duchenne who are at least 4 years of age and conditionally approved for non-ambulant individuals with Duchenne.
There are multiple other companies focused on developing genetic based therapies that target dystrophin mechanisms and non-dystrophin mechanisms for the treatment of DMD.
We have received orphan drug status for deramiocel for the treatment of DMD.
Congress has only authorized the rare pediatric disease priority review voucher program until September 30, 2024.
However, if a drug candidate receives Rare Pediatric Disease designation before September 30, 2024, it is eligible to receive a voucher if it is approved before September 30, 2026.
This program has been subject to criticism, including by the FDA, and it is possible that even if we obtain approval for deramiocel and qualify for such a Priority Review Voucher, the program may no longer be in effect at the time of approval.
As part of Project NextGen, the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health, will conduct a Phase 1 clinical study with our StealthX™ vaccine, subject to regulatory approval.
NIAID's Division of Microbiology and Infectious Diseases (“DMID”) would oversee the study.
Furthermore, the FDA may determine that results of clinical trials do not support approval for the product.

and 89 more.

Sentence-level comparison of Item 1A in the two most recent 10-Ks (FY2024 ↗, FY2025 ↗). A reworded sentence counts as one dropped and one added, so heavy edits read as low “kept”. Headings and page furniture are stripped; nothing is summarised by a model.

Watch CAPR. Know when insiders buy.

One email the day a filing lands. Free.