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What changed in X4 Pharmaceuticals, Inc's 10-K — 2023 vs 2024

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Paragraph-level year-over-year comparison of X4 Pharmaceuticals, Inc's 2023 and 2024 10-K annual filings, covering the Business, Risk Factors, Legal Proceedings, Cybersecurity, MD&A and Market Risk sections. Every new, removed and edited paragraph is highlighted side-by-side so you can see exactly what management changed in the 2024 report.

+502 added−516 removedSource: 10-K (2025-03-26) vs 10-K (2024-03-21)

Top changes in X4 Pharmaceuticals, Inc's 2024 10-K

502 paragraphs added · 516 removed · 339 edited across 7 sections

Item 1. Business

Business — how the company describes what it does

109 edited+55 added−71 removed181 unchanged
Biggest changeIn December 2022, we presented results from what we believe was the first study examining the prevalence of chronic neutropenia disorders (including idiopathic, cyclic, and congenital neutropenia) in the United States; we believe that determining the estimated projected prevalence of chronic neutropenic disorders is a key step to understanding the extent of existing unmet medical needs in this patient population. • Using a retrospective analysis of a large U.S. claims database, the analysis included people with a diagnosis code for neutropenia during the calendar years 2018, 2019, and 2021 (the year 2020 was excluded from this analysis owing to anticipated reduced claims during the COVID-19 pandemic). • People with a diagnostic, procedural, or product code for neutropenia resulting from secondary causes including chemotherapy, drug exposure, infection, solid organ transplantation, myelodysplastic syndrome, and end-stage renal disease within 24-month period prior to selection were excluded. • A 13- to 24-month look back period prior to index date was used to confirm chronic status. • The analysis used longitudinal prescription data and office-based claims data from an IQVIA claims database that included 93% of retail prescription claims, 77% of mail-in prescription claims, and had more than 1.5 billion office-based claims per year. • This retrospective analysis projected that in 2021, up to 48,000 people in the United States were living with a diagnosis of chronic neutropenia, with the most common type of chronic neutropenic disorder being idiopathic (~40,000), followed by cyclic (~5,000), and congenital (~3,000), and with the majority of affected people being female adults.
Biggest changeIn December 2022, we presented results from what we believe was the first study examining the prevalence of chronic neutropenia disorders (including idiopathic, cyclic, and congenital neutropenia) in the United States; we believe that determining the estimated projected prevalence of chronic neutropenic disorders is a key step to understanding the extent of existing unmet medical needs in this patient population. • Using a retrospective analysis of a large U.S. claims database, the analysis included people with a diagnosis code for neutropenia during the calendar years 2018, 2019, and 2021 (the year 2020 was excluded from this analysis owing to anticipated reduced claims during the COVID-19 pandemic). • People with a diagnostic, procedural, or product code for neutropenia resulting from secondary causes including chemotherapy, drug exposure, infection, solid organ transplantation, myelodysplastic syndrome, and end-stage renal disease within 24-month period prior to selection were excluded. • A 13- to 24-month look back period prior to index date was used to confirm chronic status. • The analysis used longitudinal prescription data and office-based claims data from an IQVIA claims database that included 93% of retail prescription claims, 77% of mail-in prescription claims, and had more than 1.5 billion office-based claims per year. • This retrospective analysis projected that in 2021, up to 48,000 people in the United States were living with a diagnosis of chronic neutropenia, with the most common type of chronic neutropenic disorder being idiopathic (~40,000), followed by cyclic (~5,000), and congenital (~3,000), and with the majority of affected people being female adults. 8 • Our research into the estimated individuals in the U.S. diagnosed with chronic neutropenia confirmed that significant unmet medical needs exist despite the availability and use of G-CSF and, if our analysis is correct, this suggests a potential minimal addressable market for mavorixafor of approximately one third of this population, or approximately 15,000 individuals in the U.S., plus meaningful potential market expansion opportunities.
The diagnosis of WHIM syndrome may occur at any age: about one-half of reported patients are diagnosed as children, primarily before of at the age of 18 years, with the other half diagnosed as adults, mostly between 18 and 40 years of age.
The diagnosis of WHIM syndrome may occur at any age: about one-half of reported patients are diagnosed as children, primarily before the age of 18 years, with the other half diagnosed as adults, mostly between 18 and 40 years of age.
Importantly, the single Grade 3 infection in the mavorixafor treatment arm occurred during the first 3 months of the trial; after 3 months of treatment, there were no serious infections in the mavorixafor-arm, whereas the frequency of severe infections in those on placebo remained unchanged over the 52-week trial period. • Duration of Infections: In the trial, mavorixafor treatment reduced the total duration (in days) of infections by more than 70% as compared to placebo, with those on placebo experiencing a mean of 7 weeks (49.1 days) with infections over the 52-week trial period versus a mean of only 2 weeks (14.1 days) with infections for those treated with mavorixafor. • Other Infection Metrics: Mavorixafor treatment resulted in a 40% lower total infection score, a metric that combines infection number and severity (LS mean [95% CI]: mavorixafor, 7.41 [1.64–13.19]; placebo, 12.27 [7.24–17.30]).
Importantly, the single Grade 3 infection in the mavorixafor treatment arm occurred during the first 3 months of the trial; after 3 months of treatment, there were no serious infections in the mavorixafor-arm, whereas the frequency of severe infections in those on placebo remained unchanged over the 52-week trial period. • Duration of Infections: In the trial, mavorixafor treatment reduced the total duration (in days) of infections by more than 70% as compared to placebo, with those on placebo experiencing a mean of 7 weeks (49.1 days) with infections over the 52-week trial period versus a mean of only 2 weeks (14.1 days) with infections for those treated with 7 mavorixafor. • Other Infection Metrics: Mavorixafor treatment resulted in a 40% lower total infection score, a metric that combines infection number and severity (LS mean [95% CI]: mavorixafor, 7.41 [1.64–13.19]; placebo, 12.27 [7.24–17.30]).
People living with chronic neutropenia have few treatment options and may be treated with G-CSF, an injectable therapy approved in the United States for the treatment of severe, chronic neutropenia. G-CSF is used to stimulate the bone marrow to produce neutrophils. Side effects of G-CSF include disabling bone pain, which can be more severe in certain age groups.
People living with chronic neutropenia have few treatment options and may be treated with G-CSF, an injectable therapy approved in the United States for the treatment of severe, chronic neutropenia. G-CSF is used to stimulate bone marrow to produce neutrophils. Side effects of G-CSF include disabling bone pain, which can be more severe in certain age groups.
Manufacturing We do not own or operate, and currently have no plans to establish, manufacturing facilities for the production of clinical or commercial quantities of mavorixafor or any of our other product candidates. We currently rely, and expect to continue to rely, on third parties for the manufacture of any of our product or product candidates.
Manufacturing We do not own or operate, and currently have no plans to establish, manufacturing facilities for the production of clinical or commercial quantities of mavorixafor or any of our other product candidates. We currently rely on and expect to continue to rely on, third parties for the manufacture of any of our product or product candidates.
If a drug demonstrates evidence of effectiveness and an acceptable safety profile in Phase 2 evaluations, Phase 3 trials are undertaken to obtain the additional information about clinical efficacy and safety in a larger number of patients, typically at geographically dispersed clinical trial sites, to permit the FDA to evaluate the overall benefit-risk relationship of the drug and to provide adequate information for the labeling of the drug.
If a drug demonstrates evidence of effectiveness and an acceptable safety profile in Phase 2 evaluations, Phase 3 trials are undertaken to obtain additional information about clinical efficacy and safety in a larger number of patients, typically at geographically dispersed clinical trial sites, to permit the FDA to evaluate the overall benefit-risk relationship of the drug and to provide adequate information for the labeling of the drug.
The laws that may affect our ability to operate include: • the federal Anti-Kickback Statute, which prohibits, among other things, persons from knowingly and willfully soliciting, receiving, offering or paying remuneration, directly or indirectly, to induce, or in return for, the purchase or recommendation of an item or service reimbursable under a federal healthcare program, such as the Medicare and Medicaid programs; • federal civil and criminal false claims laws and civil monetary penalty laws, which prohibit, among other things, individuals or entities from knowingly presenting, or causing to be presented, claims for payment from Medicare, Medicaid, or other third-party payors that are false or fraudulent; • the federal Health Insurance Portability and Accountability Act of 1996 (“HIPAA”), which created additional federal criminal statutes that prohibit, among other things, executing a scheme to defraud any healthcare benefit program and making false statements relating to healthcare matters; • the federal transparency laws, including the federal Physician Payments Sunshine Act, that require drug manufacturers to disclose payments and other transfers of value provided to physicians, (currently defined to include doctors, dentists, optometrists, podiatrists and chiropractors), certain other healthcare professionals (such as physician assistants and nurse practitioners) and teaching hospitals, as well as ownership and investment interests held by physicians and their immediate family members; • HIPAA, as amended by the Health Information Technology and Clinical Health Act (“HITECH”), and its implementing regulations, which imposes certain requirements on “covered entities,” including certain healthcare providers, health plans, and healthcare clearinghouses, as well as their respective “business associates” that create, receive, maintain or transmit individually identifiable health information for or on behalf of a covered entity, and their covered subcontractors, with respect to safeguarding the privacy, security and transmission of individually identifiable health information; • Federal drug price reporting laws, which require manufacturers to calculate and report complex pricing metrics to government programs, where such reported prices may be used in the calculation of reimbursement and/or discounts on approved products; and • Foreign and state law equivalents of each of the above federal laws, such as anti-kickback and false claims laws which may apply to items or services reimbursed by any third-party payor, including commercial insurers, state and local laws governing the disclosure of payments to health care professionals, state laws that require pharmaceutical companies to comply with the pharmaceutical industry’s voluntary compliance guidelines and the relevant compliance guidance promulgated by the federal government, state laws that require the reporting of information related to drug pricing, state and local laws requiring the registration of pharmaceutical sales representatives and state laws governing the privacy and security of health information in certain circumstances, many of which differ from each other in significant ways and may not have the same effect, thus complicating compliance efforts.
The laws that may affect our ability to operate include: • t he federal Anti-Kickback Statute, which prohibits, among other things, persons from knowingly and willfully soliciting, receiving, offering or paying remuneration, directly or indirectly, to induce, or in return for, the purchase or recommendation of an item or service reimbursable under a federal healthcare program, such as the Medicare and Medicaid programs; • federal civil and criminal false claims laws and civil monetary penalty laws, which prohibit, among other things, individuals or entities from knowingly presenting, or causing to be presented, claims for payment from Medicare, Medicaid, or other third-party payors that are false or fraudulent; • the federal Health Insurance Portability and Accountability Act of 1996 (“HIPAA”), which created additional federal criminal statutes that prohibit, among other things, executing a scheme to defraud any healthcare benefit program and making false statements relating to healthcare matters; • the federal transparency laws, including the federal Physician Payments Sunshine Act, that require drug manufacturers to disclose payments and other transfers of value provided to physicians, (currently defined to include doctors, dentists, optometrists, podiatrists and chiropractors), certain other healthcare professionals (such as physician assistants and nurse practitioners) and teaching hospitals, as well as ownership and investment interests held by physicians and their immediate family members; • HIPAA, as amended by the Health Information Technology and Clinical Health Act (“HITECH”), and its implementing regulations, which imposes certain requirements on “covered entities,” including certain healthcare providers, health plans, and healthcare clearinghouses, as well as their respective “business associates” that create, receive, maintain or transmit individually identifiable health information for or on behalf of a covered entity, and their covered subcontractors, with respect to safeguarding the privacy, security and transmission of individually identifiable health information; • Federal drug price reporting laws, which require manufacturers to calculate and report complex pricing metrics to government programs, where such reported prices may be used in the calculation of reimbursement and/or discounts on approved products; and • Foreign and state law equivalents of each of the above federal laws, such as anti-kickback and false claims laws which may apply to items or services reimbursed by any third-party payor, including commercial insurers, state and local laws governing the disclosure of payments to health care professionals, state laws that require pharmaceutical companies to comply with the pharmaceutical industry’s voluntary compliance guidelines and the relevant compliance guidance promulgated by the federal government, state laws that require the reporting of information related to drug pricing, state and local laws requiring the registration of pharmaceutical sales representatives and state laws governing the privacy and security of health information in certain circumstances, many of which differ from each other in significant ways and may not have the same effect, thus complicating compliance efforts.
European Union Orphan Designation and Exclusivity In the EU, the European Commission grants orphan designation in respect of a product, after receiving the opinion of the EMA’s Committee for Orphan Medicinal Products, if its sponsor can establish that: (1) the product is intended for the diagnosis, prevention or treatment of a life-threatening or chronically debilitating condition; (2) either (i) such condition affects no more than five in 10,000 persons in the EU when the application is made, or (ii) it is unlikely that the product, without the benefits derived from orphan status, would generate sufficient return in the EU to justify the necessary investment in its development; and (3) there exists no satisfactory method of diagnosis, prevention or treatment of such condition authorized for marketing in the EU, or, if such a method exists, the product would be a significant benefit to those affected by that condition.
European Union Orphan Designation and Exclusivity In the EU, the European Commission grants orphan designation in respect of a product, after receiving the opinion of the EMA’s Committee for Orphan Medicinal Products, if its sponsor can establish that: (1) the product is intended for the diagnosis, 22 prevention or treatment of a life-threatening or chronically debilitating condition; (2) either (i) such condition affects no more than five in 10,000 persons in the EU when the application is made, or (ii) it is unlikely that the product, without the benefits derived from orphan status, would generate sufficient return in the EU to justify the necessary investment in its development; and (3) there exists no satisfactory method of diagnosis, prevention or treatment of such condition authorized for marketing in the EU, or, if such a method exists, the product would be a significant benefit to those affected by that condition.
The main characteristics of the new Regulation include: a streamlined application procedure via a single-entry point through the Clinical Trials Information System (“CTIS”); a single set of documents to be prepared and submitted for the application as well as simplified reporting procedures for clinical trial sponsors; and a harmonized procedure for the assessment of applications for clinical trials, which is divided in two parts (Part I contains scientific and medicinal product documentation and Part II contains the national and patient-level documentation).
The main characteristics of the Regulation include: a streamlined application procedure via a single-entry point through the Clinical Trials Information System (“CTIS”); a single set of documents to be prepared and submitted for the application as well as simplified reporting procedures for clinical trial sponsors; and a harmonized procedure for the assessment of applications for clinical trials, which is divided in two parts (Part I contains scientific and medicinal product documentation and Part II contains the national and patient-level documentation).
License Agreement License Agreement with Genzyme In July 2014, we entered into a license agreement with Genzyme Corporation (“Genzyme”), a wholly owned subsidiary of Sanofi, pursuant to which we were granted an exclusive license to certain patent applications and other intellectual property owned or controlled by Genzyme related to the CXCR4 receptor to develop and commercialize products containing licensed compounds, including but not limited to, mavorixafor.
License Agreements License Agreement with Genzyme In July 2014, we entered into a license agreement with Genzyme Corporation (“Genzyme”), a wholly owned subsidiary of Sanofi, pursuant to which we were granted an exclusive license to certain patent applications and other intellectual property owned or controlled by Genzyme related to the CXCR4 receptor to develop and commercialize products containing licensed compounds, including but not limited to, mavorixafor.
EU Directive 2001/83/EC, which is the EU Directive governing medicinal products for human use, further provides that, where medicinal products are being promoted to persons qualified to prescribe or supply them, no gifts, pecuniary advantages, or benefits in kind may be supplied, offered or 24 promised to such persons unless they are inexpensive and relevant to the practice of medicine or pharmacy.
EU Directive 2001/83/EC, which is the EU Directive governing medicinal products for human use, further provides that, where medicinal products are being promoted to persons qualified to prescribe or supply them, no gifts, pecuniary advantages, or benefits in kind may be supplied, offered or promised to such persons unless they are inexpensive and relevant to the practice of medicine or pharmacy.
Clinical trials are typically conducted in three sequential phases, but the phases may overlap. In general, in Phase 1, the initial introduction of the drug into healthy human volunteers or, in some cases, patients, the drug is tested to assess metabolism, pharmacokinetics, pharmacological actions, side effects associated with increasing doses and, if possible, early evidence of 18 effectiveness.
Clinical trials are typically conducted in three sequential phases, but the phases may overlap. In general, in Phase 1, the initial introduction of the drug into healthy human volunteers or, in some cases, patients, the drug is tested to assess metabolism, pharmacokinetics, pharmacological actions, side effects associated with increasing doses and, if possible, early evidence of effectiveness.
The overall ten-year period will be extended to a maximum of eleven years if, during the first eight years of those ten years, the MA holder obtains an MA for one or more new therapeutic indications which, during the scientific evaluation prior to their MA, are determined to bring a significant clinical benefit in comparison with currently approved therapies.
The overall ten-year period will be extended to a maximum of eleven years if, during the first eight years of those ten years, the MA holder obtains an MA for one or more new therapeutic indications which, during the scientific evaluation prior to their authorization, are determined to bring a significant clinical benefit in comparison with currently approved therapies.
In addition, because of the extensive time required for clinical development and regulatory review of a product candidate we may develop, it is possible that, before any of our product candidates can be commercialized, any related patent may expire or remain in force for only a short period following commercialization, thereby reducing any 17 advantage of any such patent.
In addition, because of the extensive time required for clinical development and regulatory review of a product candidate we may develop, it is possible that, before any of our product candidates can be commercialized, any related patent may expire or remain in force for only a short period following commercialization, thereby reducing any advantage of any such patent.
Because antagonism of the CXCR4 receptor has been shown to increase the trafficking of white blood cells, we believe that therapeutic inhibition of the 5 CXCR4/CXCL12 axis holds the potential to benefit people with a wide variety of diseases where there remain significant unmet needs, including chronic neutropenic disorders and certain types of cancer.
Because antagonism of the CXCR4 receptor has been shown to increase the trafficking of white blood cells, we believe that therapeutic inhibition of the CXCR4/CXCL12 axis holds the potential to benefit people with a wide variety of diseases where there remain significant unmet needs, including chronic neutropenic disorders and certain types of cancer.
In order to obtain coverage and reimbursement for any product that might be approved for sale, we may need to conduct expensive pharmacoeconomic studies in order to demonstrate the medical necessity and cost-effectiveness of our products, in addition to the costs required to obtain regulatory approvals. Our product candidates may not be considered medically necessary or cost-effective.
In order to obtain coverage and reimbursement for any product that 24 might be approved for sale, we may need to conduct expensive pharmacoeconomic studies in order to demonstrate the medical necessity and cost-effectiveness of our products, in addition to the costs required to obtain regulatory approvals. Our product candidates may not be considered medically necessary or cost-effective.
In September 2022, we announced positive results from the Phase 1b clinical trial: • A total of 25 participants were enrolled in the study. • 100% of study participants responded to treatment with a single dose of 400 mg of mavorixafor, alone or dosed concurrently with G-CSF: ◦ Participants achieved a mean ANC increase at peak of >3,000 cells per microliter. ◦ Consistent responses were seen across all of the chronic neutropenic disorders studied – idiopathic, cyclic, and congenital neutropenia. • All neutropenic participants (n=14) reached normalized ANC levels (>1,500 cells per microliter): ◦ When assessed as a monotherapy in participants with severe chronic neutropenia who were not being treated with G-CSF (n=6), a single dose of mavorixafor led to normalized ANC levels in all participants within 2 hours, with a mean ANC increase at peak of ~2,500 cells per microliter. ◦ When assessed in participants with moderate or severe neutropenia, despite being treated with G-CSF (n=8), 100% reached normalized ANC levels, suggesting the potential of mavorixafor to both normalize the neutrophil counts in patients with partial response to G-CSF and also to potentially enable the reduction or elimination of G-CSF dosing. • When assessed in participants with chronic neutropenia with normalized ANC counts on chronic G-CSF (n=11), all participants experienced a consistent and sustained increase in ANC, suggesting mavorixafor’s potential to reduce or possibly eliminate G-CSF treatment in these patients. • Mavorixafor was well tolerated in the study; all treatment-related adverse events were deemed to be low grade, consistent with previous clinical studies in WHIM syndrome, and no treatment-related serious adverse events were reported.
In September 2022, we announced positive results from this Phase 1b clinical trial, which enrolled a total of 25 participants: • 100% of study participants responded to treatment with a single dose of 400 mg of mavorixafor, alone or dosed concurrently with G-CSF: ▪ Participants achieved a mean ANC increase at peak of >3,000 cells per microliter. ▪ Consistent responses were seen across all of the chronic neutropenic disorders studied – idiopathic, cyclic, and congenital neutropenia. • All neutropenic participants (n=14) reached normalized ANC levels (>1,500 cells per microliter): ▪ When assessed as a monotherapy in participants with severe chronic neutropenia who were not being treated with G-CSF (n=6), a single dose of mavorixafor led to normalized ANC levels in all participants within 2 hours, with a mean ANC increase at peak of ~2,500 cells per microliter. ▪ When assessed in participants with moderate or severe neutropenia despite being treated with G-CSF (n=8), 100% reached normalized ANC levels, suggesting the potential of mavorixafor to both normalize the neutrophil counts in patients with partial response to G-CSF and also to potentially enable the reduction or elimination of G-CSF dosing. • When assessed in participants with chronic neutropenia with normalized ANC counts on chronic G-CSF (n=11), all participants experienced a consistent and sustained increase in ANC, suggesting mavorixafor’s potential to reduce or possibly eliminate G-CSF treatment in these patients. • Mavorixafor was well tolerated in the study; all treatment-related adverse events were deemed to be low grade, 9 consistent with previous clinical studies in WHIM syndrome, and no treatment-related serious adverse events were reported.
As a result, the CXCR4 receptor is maintained on the surface of the cell and is exposed to the ligand, which creates a perpetual “on” signal and retention of white blood cells in the bone marrow where they are produced, leading to the chronic peripheral neutropenia, lymphopenia, and monocytopenia that are the clinical hallmarks of WHIM syndrome.
As a result, the CXCR4 receptor is maintained on the surface of the cell and is exposed to the ligand, which creates a perpetual “on” signal and retention of white blood cells in the bone marrow where they are produced, leading to the chronic peripheral neutropenia and lymphopenia that are the clinical hallmarks of WHIM syndrome.
In the European Union, the downward pressure on healthcare costs in general, particularly prescription medicines, has become intense. As a result, barriers to entry of new products are becoming increasingly high and patients are unlikely to use a drug product that is not reimbursed by their government.
In the European Union, 25 the downward pressure on healthcare costs in general, particularly prescription medicines, has become intense. As a result, barriers to entry of new products are becoming increasingly high and patients are unlikely to use a drug product that is not reimbursed by their government.
We face potential competition from many different sources, including major pharmaceutical, specialty pharmaceutical and biotechnology companies, academic institutions, governmental agencies, and public and private research institutions. Any product candidates that we successfully develop and commercialize will compete with existing therapies and new therapies that may become available in the future.
We face potential competition from many different sources, including major 10 pharmaceutical, specialty pharmaceutical and biotechnology companies, academic institutions, governmental agencies, and public and private research institutions. Any product candidates that we successfully develop and commercialize will compete with existing therapies and new therapies that may become available in the future.
Clinical trials must be conducted in compliance with applicable federal regulations, including good clinical practices, which are meant to protect the rights and safety of study subjects and ensure the integrity of the data generated in the clinical trials and under protocols detailing the objectives of the trial, the parameters to be used in monitoring safety and the effectiveness criteria to be evaluated.
Clinical trials must be conducted in compliance with applicable federal regulations, including good clinical practices, which are meant to protect the rights and safety of study subjects and ensure the integrity of the data generated in the clinical trials and under protocols detailing the objectives of the trial, the parameters to be used in monitoring safety and the 16 effectiveness criteria to be evaluated.
The primary endpoint of the trial is a two-component endpoint that includes the annualized infection rate and ANC response in the mavorixafor-treated group versus the placebo group. Secondary endpoints are expected to include analysis of the severity and duration of infections, antibiotic use, fatigue, and quality of life parameters.
The primary endpoint of the trial is a two-component endpoint that includes the annualized infection rate and ANC response in the mavorixafor-treated group versus the placebo group. Key secondary endpoints are expected to include analysis of the severity and duration of infections, antibiotic use, fatigue, and quality of life parameters.
REMS can include medication guides, communication plans for health care professionals, and elements to assure safe use (“ETASU”). ETASU can include, but are not limited to, special training or certification for prescribing or dispensing, dispensing only under certain circumstances, special monitoring, and the use of patient registries.
REMS can include medication guides, communication plans for health care professionals, and elements to assure safe use (“ETASU”). ETASU can include, but are not limited to, special training 17 or certification for prescribing or dispensing, dispensing only under certain circumstances, special monitoring, and the use of patient registries.
Orphan drug 21 designation must be requested before submitting an NDA. After the FDA grants orphan drug designation, the generic identity of the drug and its designated orphan use are disclosed publicly by the FDA. Orphan drug designation does not convey any advantage in, or shorten the duration of, the regulatory review and approval process.
Orphan drug designation must be requested before submitting an NDA. After the FDA grants orphan drug designation, the generic identity of the drug and its designated orphan use are disclosed publicly by the FDA. Orphan drug designation does not convey any advantage in, or shorten the duration of, the regulatory review and approval process.
Moreover, while the MMA applies only to drug benefits for Medicare beneficiaries, private payors often follow Medicare coverage policy and payment limitations in setting their own payment rates. 25 Any reduction in payment that results from the MMA may result in a similar reduction in payments from non-governmental payors.
Moreover, while the MMA applies only to drug benefits for Medicare beneficiaries, private payors often follow Medicare coverage policy and payment limitations in setting their own payment rates. Any reduction in payment that results from the MMA may result in a similar reduction in payments from non-governmental payors.
We believe that this is due to the relatively recent elucidation of the genetics underlying WHIM syndrome, lack of universal or accessible genetic testing, and limited medical education and awareness of the disease, which is in part driven by the lack of available disease-modifying treatments.
We believe that this is due to the relatively recent elucidation of the genetics underlying WHIM syndrome, lack of universal or accessible genetic testing, and limited medical education and awareness of the disease, which is in part driven by the previous lack of available disease-modifying treatments.
Patents issued from our co-owned portfolio, if all maintenance fees are paid, 16 are expected to expire in 2036, not including any Patent Term Adjustment (PTA), Patent Term Extension (PTE), or other extensions of term that may be available.
Patents issued from our co-owned portfolio, if all maintenance fees are paid, are expected to expire in 2036, not including any Patent Term Adjustment (PTA), Patent Term Extension (PTE), or other extensions of term that may be available.
Other firms also compete with us in recruiting and retaining qualified scientific and management personnel and establishing clinical trial sites and patient enrollment for clinical trials, as well as in acquiring technologies complementary to, or 12 necessary for, our programs.
Other firms also compete with us in recruiting and retaining qualified scientific and management personnel and establishing clinical trial sites and patient enrollment for clinical trials, as well as in acquiring technologies complementary to, or necessary for, our programs.
During the additional two-year period of market exclusivity, a generic or biosimilar MA application can be submitted and authorized, and the innovator’s data may be referenced, 23 but no generic or biosimilar product can be placed on the EU market until the expiration of the market exclusivity.
During the additional two-year period of market exclusivity, a generic or biosimilar MA application can be submitted and authorized, and the innovator’s data may be referenced, but no generic or biosimilar product can be placed on the EU market until the expiration of the market exclusivity.
Genzyme has retained the non-exclusive right to conduct preclinical research involving compounds in any field, including any fields licensed to us, but has not retained rights to conduct any clinical development or commercialization of those compounds identified in the agreement in any of the fields licensed to us.
Genzyme has retained the non-exclusive right to conduct preclinical research involving 11 compounds in any field, including any fields licensed to us, but has not retained rights to conduct any clinical development or commercialization of those compounds identified in the agreement in any of the fields licensed to us.
For example, prior to March 16, 2013, in the United States, patent applications were subject to a “first to invent” rule of law. Applications filed after March 16, 2013 (except for certain applications claiming the benefit of earlier-filed applications) are subject to a “first to file” rule of law.
For example, prior to March 16, 2013, in the United States, patent applications were subject to a “first to invent” rule of law. Applications filed after March 16, 2013 (except for certain applications claiming the 15 benefit of earlier-filed applications) are subject to a “first to file” rule of law.
WHIM syndrome is named for its four common manifestations, although not all patients experience all symptoms, and not all symptoms are required for a diagnosis: W arts, related to infection with the Human Papilloma Virus (HPV), H ypogammaglobulinemia, a condition of low immunoglobulin (“IG”) levels, I nfections, including both bacterial and fungal infections, and M yelokathexis, a hyper-dense population of immune cells in the bone marrow.
WHIM syndrome is named for its four common manifestations, although not all patients experience all symptoms, and not all symptoms are required for a diagnosis: W arts, related to infection with the Human Papilloma Virus (“HPV”), H ypogammaglobulinemia, a condition of low immunoglobulin (“IG”) levels, I nfections, including both bacterial and fungal infections, and M yelokathexis, a hyper-dense population of immune cells in the bone marrow.
Other than bioequivalence testing, ANDA applicants are not required to conduct, or submit results of, pre-clinical or clinical tests to demonstrates the safety or effectiveness of their drug 19 product.
Other than bioequivalence testing, ANDA applicants are not required to conduct, or submit results of, pre-clinical or clinical tests to demonstrates the safety or effectiveness of their drug product.
These provisions will take effect progressively starting in fiscal year 2023, although the implementation of the IRA is currently subject to ongoing litigation that challenges the constitutionality of the IRA’s Medicare drug price negotiation program. It is currently unclear how the IRA will be implemented but is likely to have a significant impact on the pharmaceutical industry.
These provisions have taken effect progressively starting in fiscal year 2023, although the implementation of the IRA is currently subject to ongoing litigation that challenges the constitutionality of the IRA’s Medicare drug price negotiation program. It is currently unclear how the IRA will be implemented but is likely to have a significant impact on the pharmaceutical industry.
Treatment with mavorixafor also resulted in reductions in upper and lower respiratory tract and skin infections compared with those on placebo; participants on placebo required greater medical intervention, with 10 of the 17 participants on placebo requiring treatment with antibiotics over the course of the study, versus 3 of the 14 receiving mavorixafor; and slight improvements in warts were demonstrated both in the mavorixafor and placebo arms (no difference between arms). • Safety and Tolerability: As reported previously, mavorixafor was generally well tolerated in the 4WHIM trial, with no drug-related serious adverse events, no treatment limiting toxicities, and no discontinuations due to safety.
Treatment with mavorixafor also resulted in reductions in upper and lower respiratory tract and skin infections compared with those on placebo; participants on placebo required greater medical intervention, with 10 of the 17 participants on placebo requiring treatment with antibiotics over the course of the study, versus 3 of the 14 receiving mavorixafor; and slight improvements in warts were demonstrated both in the mavorixafor and placebo arms (no difference between arms). • Safety and Tolerability: Mavorixafor was generally well tolerated in the 4WHIM trial, with no drug-related serious adverse events, no treatment limiting toxicities, and no discontinuations due to safety.
The FDA will attempt to direct additional resources to the evaluation of an application for a new drug designated for priority review to facilitate the review.
The FDA will attempt to direct additional 20 resources to the evaluation of an application for a new drug designated for priority review to facilitate the review.
With respect to foreign patent rights to our developmental compounds, including preclinical candidates for our X4P-002 and XP-003 programs, we have approximately 50 pending PCT and foreign patents and patent applications. The term of individual patents depends upon the legal term of the patents in the countries in which they are obtained.
With respect to foreign patent rights to our developmental compounds, including preclinical candidates for our X4P-002 and XP-003 programs, we have approximately 22 pending PCT and foreign patents and patent applications. The term of individual patents depends upon the legal term of the patents in the countries in which they are obtained.
With respect to our lead product mavorixafor, as of December 31, 2023, we owned or exclusively licensed five issued U.S. patents and one pending U.S. non-provisional patent application that relate to mavorixafor composition of matter; one issued U.S. patent, one pending PCT application, and three pending foreign priority patent applications that relate to methods of manufacturing mavorixafor, including certain key intermediate molecules; two issued U.S. patents and one pending U.S. non-provisional patent application that relate to the use of mavorixafor for treatment of patients with WHIM Syndrome; one pending U.S. non-provisional patent application, one pending PCT application, and one pending U.S. provisional patent application that relate to the use of mavorixafor for treatment of patients with conditions involving chronic neutropenia; and three U.S. issued patents, one pending U.S. non-provisional patent application, and three pending PCT applications that relate to uses of mavorixafor in other fields, including oncology.
With respect to our lead product mavorixafor, as of December 31, 2024, we owned or exclusively licensed five issued U.S. patents and one pending U.S. non-provisional patent application that relate to mavorixafor composition of matter; two issued U.S. patents, three pending PCT applications, one pending U.S. non-provisional patent application, and 27 pending foreign patent applications that relate to methods of manufacturing mavorixafor, including certain key intermediate molecules; two issued U.S. patents and one pending U.S. non-provisional patent application that relate to the use of mavorixafor for treatment of patients with WHIM Syndrome; two pending U.S. non-provisional patent application, one pending PCT application, and one pending U.S. provisional patent application that relate to the use of mavorixafor for treatment of patients with conditions involving chronic neutropenia; and two U.S. issued patents, and three pending U.S. non-provisional patent applications, that relate to uses of mavorixafor in other fields, including oncology.
If so designated, the FDA shall act to expedite the development and review of the product ’ s marketing application, including by meeting with the sponsor throughout the product ’ s development, providing timely advice to the sponsor to ensure that the development program to gather pre-clinical and clinical data is as efficient as practicable, involving senior managers and experienced review staff in a cross-disciplinary review, assigning a cross-disciplinary project lead for the FDA review team to facilitate an efficient review of the development program and to serve as a scientific liaison between the review team and the sponsor, and taking steps to ensure that the design of the clinical trials is as efficient as practicable.
If so designated, the FDA shall act to expedite the development and review of the product’s marketing application, including by meeting with the sponsor throughout the product’s development, providing timely advice to the sponsor to ensure that the development program to gather pre-clinical and clinical data is as efficient as practicable, involving senior managers and experienced review staff in a cross-disciplinary review, assigning a cross-disciplinary project lead for the FDA review team to facilitate an efficient review of the development program and to serve as a scientific liaison between the review team and the sponsor, and taking steps to ensure that the design of the clinical trials is as efficient as practicable.
In the EU, orphan designation entitles a party to financial incentives such as reduction of fees or fee waivers and 10 years of market exclusivity is granted following the grant of an MA.
In the EU, orphan designation entitles a party to financial incentives such as reduction of fees or fee waivers and ten years of market exclusivity is granted following the grant of an MA.
A sponsor may request that a product candidate be designated as a breakthrough therapy concurrently with the submission of an IND or any time afterward, but ideally before an end-of-Phase-2 meeting. The FDA must determine if the product candidate qualifies for Breakthrough Therapy designation within 60 days of receipt of the sponsor ’ s request.
A sponsor may request that a product candidate be designated as a breakthrough therapy concurrently with the submission of an IND or any time afterward, but ideally before an end-of-Phase-2 meeting. The FDA must determine if the product candidate qualifies for Breakthrough Therapy designation within 60 days of receipt of the sponsor’s request.
The issued U.S. patents covering aspects of mavorixafor and its use, if all maintenance fees are paid, and pending applications, if granted and all maintenance fees paid, are expected to expire between 2024 and 2044, not including any Patent Term Adjustment (PTA), Patent Term Extension (PTE), or other extensions of term that may be available.
The issued U.S. patents covering aspects of mavorixafor and its use, if all maintenance fees are paid, and pending applications, if granted and all maintenance fees paid, are expected to expire between 2024 and 2044, not including any (PTA), (PTE) or other extensions of term that may be available.
In addition, the Inflation Reduction Act of 2022 (“IRA”), among other things, extends enhanced subsidies for individuals purchasing health insurance coverage in ACA marketplaces through plan year 2025.
In addition, the Inflation Reduction Act of 2022 (“IRA”), among other things, extended enhanced subsidies for individuals purchasing health insurance coverage in ACA marketplaces through plan year 2025.
In addition, we have also completed a study using artificial intelligence, interrogating a database of approximately 300 million American lives that included up to 10 years of insurance claims on diagnoses, drug treatments, procedures, and treatment pathways. This study suggests that there may be as many as 3,700 WHIM patients in the United States based on the WHIM-like phenotypes described.
We also completed a study using artificial intelligence, interrogating a database of approximately 300 million American lives that included up to 10 years of insurance claims on diagnoses, drug treatments, procedures, and treatment pathways. This study suggested that there may be as many as 3,700 WHIM patients in the United States based on the WHIM-like phenotypes described.
The centralized MA is issued by the European Commission through the centralized procedure, based on the opinion of the Committee for Medicinal Products for Human Use (“CHMP”), of the EMA, and is valid throughout the entire territory of the EU and the additional Member States of the European Economic Area (Iceland, Liechtenstein and Norway) (“EEA”).
The centralized MA is issued by the European Commission through the centralized procedure, based on the opinion of the Committee for Medicinal Products for Human Use (“CHMP”), of the EMA, and is valid throughout the entire territory of the EU and the additional countries of the European Economic Area (Iceland, Liechtenstein and Norway) (“EEA”).
With respect to foreign patent rights to mavorixafor, as of December 31, 2023, we had approximately 110 pending PCT and foreign patents and patent applications.
With respect to foreign patent rights to mavorixafor, as of December 31, 2024, we had approximately 110 pending PCT and foreign patents and patent applications.
We have included our website address in this Annual Report on Form 10-K solely as an inactive textual reference. 28
We have included our website address in this Annual Report on Form 10-K solely as an inactive textual reference. 27
Human capital is critical to our success. Our overarching human capital resource strategy is to recruit, hire, incentivize and retain employees consistent with our stage of operations and strategic objectives. We believe we offer our employees compensation that is competitive and consistent with the markets in which we operate, namely the Greater Boston and the Vienna, Austria metropolitan areas.
Human capital is critical to our success. Our overarching human capital resource strategy is to recruit, hire, incentivize and retain employees consistent with our stage of operations and strategic objectives. We believe we offer our employees compensation that is competitive and consistent with the markets in which we operate, namely the Greater Boston metropolitan area.
As of December 31, 2023, we are obligated to pay Genzyme future milestone payments in the aggregate amount of up to $20 million, contingent upon our achievement of certain late-stage regulatory and sales milestones with respect to licensed products, and tiered royalties based on net sales of licensed products that we commercialize under the Genzyme agreement.
As of December 31, 2024, we are obligated to pay Genzyme future milestone payments in the aggregate amount of up to $13.0 million, contingent upon our achievement of certain late-stage regulatory and sales milestones with respect to licensed products, and tiered royalties based on net sales of licensed products that we commercialize under the Genzyme agreement.
Upon the first potential sale of our drug candidate in the U.S., we will incur a royalty on annual net sales at a rate of 6% up to $150 million, 10% on the portion of annual net sales between $150 million and $300 million, and 12% thereafter.
Upon the first potential sale of our drug candidate in the U.S., we have incurred a royalty on annual net sales at a rate of 6% up to $150 million, and would incur 10% on the portion of annual net sales between $150 million and $300 million, and 12% thereafter.
It is unclear how any such challenges and the healthcare reform measures of the Biden administration will impact the ACA. Also, there has been heightened governmental scrutiny recently over pharmaceutical pricing practices in light of the rising cost of prescription drugs and biologics.
It is unclear how any such challenges and or healthcare reform measures will impact the ACA. There has been heightened governmental scrutiny recently over pharmaceutical pricing practices in light of the rising cost of prescription drugs and biologics.
(“Catalent”), which is our sole manufacturer for the final capsule drug product formulation of mavorixafor. The term of the master services agreement with Catalent expires on September 10, 2024, and may be terminated by (1) us upon 30 days-notice to Catalent or (2) by either party following a material breach by the other party that remains uncured for 30 days.
(“Catalent”), which is our sole manufacturer for the final capsule drug product formulation of mavorixafor. The term of the master services agreement with Catalent expires on December 31, 2028 and may be terminated by (1) us upon 30 days-notice to Catalent or (2) by either party following a material breach by the other party that remains uncured for 30 days.
In April 2014, the EU adopted the new Clinical Trials Regulation (EU) No 536/2014, which replaced the Clinical Trials Directive 2001/20/EC on January 31, 2022. The transitory provisions of the new Regulation provide that, by January 31, 2025, all ongoing clinical trials must have transitioned to the new Regulation.
In April 2014, the EU adopted the Clinical Trials Regulation (EU) No 536/2014, which replaced the Clinical Trials Directive 2001/20/EC on January 31, 2022. The transitory provisions of the Regulation provide that, by January 31, 2025, all ongoing clinical trials must have transitioned to the Regulation. The Regulation overhauled the system of approvals for clinical trials in the EU.
These issued patents, if all maintenance fees are paid, and pending applications, if granted and all maintenance fees paid, are expected to expire between 2024 and 2043, not including any Patent Term Adjustment (PTA), Patent Term Extension (PTE), or other extensions of term that may be available.
These issued patents, if all maintenance fees are paid, and pending applications, if granted and all maintenance fees paid, are expected to expire between 2024 and 2045, not including any (PTA), (PTE) or other extensions of term that may be available.
The provision of benefits or advantages to physicians may be governed by the national anti-bribery laws of EU Member States, and the Bribery Act 2010 in the UK. Infringement of these laws could result in substantial fines and imprisonment.
The provision of benefits or advantages to reward improper performance generally may be governed by the national anti-bribery laws of EU Member States, and the Bribery Act 2010 in the UK. Infringement of these laws could result in substantial fines and imprisonment.
Originally designed to enroll 18-28 patients, the trial achieved full enrollment in September 2021, with 31 participants aged 12 and older receiving either 200-400 mg mavorixafor or placebo orally once daily for 52 weeks; all participants then became eligible to receive treatment with mavorixafor in an open-label trial extension.
Originally designed to enroll 18-28 patients, the trial enrolled 31 participants aged 12 and older receiving either 200 or 400 mg mavorixafor or placebo orally once daily for 52 weeks; all participants then became eligible to receive treatment with mavorixafor in an open-label trial extension (“OLE”).
While the costs of managing the chronic impact of WHIM syndrome are unknown, the per-patient cost of treating primary immunodeficiencies that are similar to WHIM syndrome, based on drug costs alone, exceeds $100,000 per year in the United States for therapies such as antibiotics, IVIG, SCIG and/or G-CSF, despite the limited effectiveness of these treatments.
While the costs of managing the chronic impact of WHIM syndrome are unknown, the per-patient cost of treating primary immunodeficiencies that are similar to WHIM syndrome, based on drug costs alone, exceeds $100,000 per year in the United States for therapies such as antibiotics, intravenous immunoglobulin (“IVIg”), subcutaneous immunoglobulin (“SCIg”) and/or injectable G-CSF, despite the limited effectiveness of these treatments.
Pharmaceutical product development in the United States typically involves preclinical or other nonclinical laboratory and animal tests and the submission to the FDA of an IND, which must become effective before clinical testing may commence.
Pharmaceutical product development in the United States typically involves preclinical or other nonclinical laboratory and animal tests and the submission to the FDA of an Investigational New Drug (“IND”) application, which must become effective before clinical testing may commence.
The new Regulation overhauled the system of approvals for clinical trials in the EU. Specifically, it is directly applicable in all Member States (meaning that no national implementing legislation in each Member State is required), and aims at simplifying and streamlining the approval of clinical trials in the EU.
Specifically, it is directly applicable in all EU Member States (meaning that no national implementing legislation in each EU Member State is required), and aims at simplifying 21 and streamlining the approval of clinical trials in the EU.
Our Focus We have developed a pipeline of small-molecule, oral antagonists of the chemokine receptor CXCR4, or C-X-C receptor type 4. CXCR4 is a cell receptor that helps regulate the movement of immune cells within the body.
Our Focus Since our inception, we have focused our business on the development of small-molecule, oral antagonists of the chemokine receptor CXCR4, or C-X-C receptor type 4. CXCR4 is a cell receptor that helps regulate the movement of immune cells within the body.
With respect to developmental compounds, including preclinical candidates for our X4P-002 and X4P-003 programs, as of December 31, 2023, we had nine issued U.S. patents, one pending U.S. non-provisional patent application, two pending U.S. provisional patent applications and two pending PCT patent applications.
With respect to developmental compounds, including preclinical candidates for our X4P-002 and X4P-003 programs, as of December 31, 2024, we had five issued U.S. patents, four pending U.S. non-provisional patent applications, three pending U.S. provisional patent applications and three pending PCT patent applications.
There can be no assurance that any country that has price controls or reimbursement limitations for pharmaceutical products will allow favorable reimbursement and pricing arrangements for any of our products. Historically, products launched in the European Union do not follow price structures of the United States.
Such differences in national pricing regimes may create price differentials between E.U. member states. There can be no assurance that any country that has price controls or reimbursement limitations for pharmaceutical products will allow favorable reimbursement and pricing arrangements for any of our products. Historically, products launched in the European Union do not follow price structures of the United States.
Changes to certain conditions established in an approved application, including changes in indications, labeling, or manufacturing processes or facilities, require submission and FDA approval of a new NDA or NDA supplement before the change can be implemented.
Prescription drug promotional materials must be submitted to the FDA at the time of their first use. Changes to certain conditions established in an approved application, including changes in indications, labeling, or manufacturing processes or facilities, require submission and FDA approval of a new NDA or NDA supplement before the change can be implemented.
Abbisko Agreement In July 2019, we entered into a license agreement with Abbisko Therapeutics Co Ltd. (“Abbisko”). Under the terms of the agreement, we granted Abbisko the exclusive right to develop, manufacture and commercialize mavorixafor in mainland China, Taiwan, Hong Kong and Macau.
We may terminate the BIDMC agreement at any time upon at least 90 days’ written notice. Abbisko Agreement In July 2019, we entered into a license agreement with Abbisko Therapeutics Co Ltd. (“Abbisko”). Under the terms of the agreement, we granted Abbisko the exclusive right to develop, manufacture and commercialize mavorixafor in mainland China, Taiwan, Hong Kong and Macau.
The requirements of regulatory authorities outside the United States are in many respects similar to those we are subject to in the United States, but in some instances the legal and regulatory requirements outside the United States may differ from or be more stringent than what we must comply with in the United States. 22 European Union Drug Development In the European Union (“ EU ”), our future products may also be subject to extensive regulatory requirements.
The requirements of regulatory authorities outside the United States are in many respects similar to those we are subject to in the United States, but in some instances the legal and regulatory requirements outside the United States may differ from or be more stringent than what we must comply with in the United States.
Bone marrow transplants bring additional risks into the management of the disorders. 11 Clinical Development of Mavorixafor in Chronic Neutropenic Disorders In 2022, we conducted a proof-of-concept Phase 1b open-label, multicenter study designed to assess the safety and tolerability of oral mavorixafor, with or without injectable G-CSF, in participants with chronic neutropenic disorders, including idiopathic, cyclic, and congenital neutropenia.
Clinical Trial Results to Date for Mavorixafor in Chronic Neutropenic Disorders In 2022, we conducted a proof-of-concept Phase 1b open-label, multicenter study designed to assess the safety and tolerability of oral mavorixafor, with or without injectable G-CSF, in participants with chronic neutropenic disorders, including idiopathic, cyclic, and congenital neutropenia.
If any of the physicians or other healthcare 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 significant criminal, civil or administrative sanctions, including exclusions from government funded healthcare programs. 27 Human Capital Policies and Procedures As of December 31, 2023, we had 93 full-time employees.
If any of the physicians or other healthcare providers or entities with whom we expect to do business is found to be 26 not in compliance with applicable laws, they may be subject to significant criminal, civil or administrative sanctions, including exclusions from government funded healthcare programs.
Our policy is to seek to protect our intellectual property position by, among other methods, filing U.S. and foreign patent applications related to the technology, inventions and improvements that are important to the development and implementation of our business strategy. We also rely on trade secrets, know-how and continuing technological innovation to develop and maintain our proprietary position.
Our policy is to seek to protect our intellectual property position by, among other methods, filing U.S. and foreign patent applications related to the technology, inventions and improvements that are important to the development and implementation of our business strategy.
Priority review vouchers may be redeemed to obtain priority review for any subsequent marketing application or be sold or transferred. Expedited Development and Review Programs The FDA has a Fast Track program that is intended to expedite or facilitate the process for development and review of new drugs that meet certain criteria.
Expedited Development and Review Programs The FDA has a Fast Track program that is intended to expedite or facilitate the process for development and review of new drugs that meet certain criteria.
Failure to comply with these requirements could result in reputational risk, public reprimands, administrative penalties, fines or imprisonment. The aforementioned EU rules are generally applicable in the EEA.
Failure to comply with these requirements could result in reputational risk, public reprimands, administrative penalties, fines or imprisonment.
As of December 31, 2023, we owned or exclusively licensed 20 issued U.S. patents, five pending U.S. non-provisional patent applications, three pending U.S. provisional patent applications, and approximately 160 PCT and foreign patents and patent applications including in the following foreign jurisdictions: Austria, Australia, Belgium, Brazil, Canada, China, Denmark, European Patent Office, Finland, France, Germany, Great Britain, Hong Kong, India, Ireland, Israel, Italy, Japan, Lichtenstein, Mexico, Netherlands, New Zealand, Norway, Poland, Portugal, Singapore, South Africa, South Korea, Spain, Sweden and Switzerland.
As of December 31, 2024, we owned or exclusively licensed 18 issued U.S. patents, 10 pending U.S. non-provisional patent applications, four pending U.S. provisional patent applications, and approximately 121 PCT and foreign patents and patent applications including in the following foreign jurisdictions: Austria, Australia, Belgium, Brazil, Canada, China, Czech Republic, Denmark, Eurasian Patent Organization, European Patent Office, Finland, France, Germany, Greece, Great Britain, Hong Kong, Hungry, India, Ireland, Israel, Italy, Japan, Kuwait, Mexico, Netherlands, New Zealand, Norway, Oman, Poland, Portugal, Qatar, Saudi Arabia, Slovakia, Slovenia, Singapore, South Africa, South Korea, Spain, Sweden, Switzerland, Turkey, and United Arab Emirates.
The IRA also eliminates the “donut hole” under the Medicare Part D program beginning in 2025 by capping the beneficiary maximum out-of-pocket cost at $2,000 per year and creating a new manufacturer discount program. It is possible that the ACA will be subject to judicial or Congressional challenges in the future.
The IRA also eliminated the “donut hole” under the Medicare Part D program (effective January 1, 2025) by capping the beneficiary maximum out-of-pocket cost at $2,000 per year and creating a new manufacturer discount program. The ACA continues to be subject to judicial or challenges and may be subject to legislative healthcare reform measures in the future.
Five-year and three-year exclusivities do not preclude FDA approval of another 505(b)(1) NDA application for the drug during the period of exclusivity, provided that the 505(b)(1) applicant conducts or obtains a right of reference to all of the preclinical studies and adequate and well controlled clinical trials necessary to demonstrate safety and effectiveness.
If there is no listed patent in the Orange Book, there may not be a Paragraph IV certification and thus no ANDA or 505(b)(2) application may be filed before the expiration of the exclusivity period. 18 Five-year and three-year exclusivities do not preclude FDA approval of another 505(b)(1) NDA application for the drug during the period of exclusivity, provided that the 505(b)(1) applicant conducts or obtains a right of reference to all of the preclinical studies and adequate and well controlled clinical trials necessary to demonstrate safety and effectiveness.
For example, President Biden has issued multiple executive orders that have sought to reduce prescription drug costs. Further, on June 17, 2021, the U.S. Supreme Court dismissed a judicial challenge on procedural grounds that argued the ACA is unconstitutional in its entirety because the “individual mandate” was repealed by Congress.
On June 17, 2021, for example, the U.S. Supreme Court dismissed a judicial challenge on procedural grounds that argued the ACA is unconstitutional in its entirety because the “individual mandate” was repealed by Congress.
During this market exclusivity period, neither the EMA nor the European Commission nor any of the competent authorities in the EU Members States can accept an application or grant an MA for a “similar medicinal product.” A “similar medicinal product” is defined as a medicinal product containing a similar active substance or substances as contained in an authorized orphan medicinal product, and which is intended for the same therapeutic indication.
During this market exclusivity period, neither the EMA nor the European Commission nor any of the competent authorities in the EU Members States can accept an application or grant an MA for a “similar medicinal product” for the authorized orphan indication.
Drugs may be marketed only for the approved indications and in a manner that is consistent with their approved labeling. Although physicians may prescribe legally available products for off-label uses, manufacturers may not market or promote such uses. Prescription drug promotional materials must be submitted to the FDA at the time of their first use.
The FDA closely regulates the post-approval marketing and promotion of drugs. Drugs may be marketed only for the approved indications and in a manner that is consistent with their approved labeling. Although physicians may prescribe legally available products for off-label uses, manufacturers may not market or promote such uses.
In partnership with Invitae, a genetic information company, we sponsor a no-charge genetic testing and counseling program called PATH4WARD for individuals who may carry a genetic variation known to be associated with chronic neutropenia or primary immunodeficiency disorders (“PIDs”), including WHIM syndrome.
To address the issue of accessible genetic testing related to WHIM syndrome, we sponsor a no-charge genetic testing and counseling program called PATH4WARD for individuals who may carry genetic variations known to be associated with chronic neutropenia or primary immunodeficiency disorders (“PIDs”), including WHIM syndrome. Our U.S.
An interim patent extension increases the patent term by one year and may be renewed up to four times. For each interim patent extension granted, the post-approval patent extension is reduced by one year.
An interim patent extension increases the patent term by one year and may be renewed up to four times. For each interim patent extension granted, the post-approval patent extension is reduced by one year. The director of the USPTO must determine that approval of the drug covered by the patent for which a patent extension is being sought is likely.
Postmarket Requirements Once an NDA is approved, the manufacturer and the product will be subject to continuing regulation by the FDA, including, among other things, monitoring and recordkeeping activities, annual report requirements, reporting of adverse experiences, and complying with promotion and advertising requirements. The FDA closely regulates the post-approval marketing and promotion of drugs.
Interim patent extensions are not available for a drug for which an NDA has not been submitted. Postmarket Requirements Once an NDA is approved, the manufacturer and the product will be subject to continuing regulation by the FDA, including, among other things, monitoring and recordkeeping activities, annual report requirements, reporting of adverse experiences, and complying with promotion and advertising requirements.
Secondary endpoints include time above threshold-absolute lymphocyte count (TAT-ALC) of ≥ 1,000 cells per microliter over a 24-hour period, a composite clinical efficacy endpoint for mavorixafor based on total infection score and total wart change score, total wart change score for mavorixafor based on central 9 blinded, independent review of 3 target skin regions, total infection score for mavorixafor based on number and severity of infections adjudicated by a blinded, independent adjudication committee; and a number of quality-of-life measurements and other exploratory endpoints.
Secondary endpoints included time above threshold for absolute lymphocyte count (“TAT-ALC”) of ≥ 1,000 cells per microliter over a 24-hour period, a composite clinical efficacy endpoint for mavorixafor based on total infection score and total wart change score, total wart change score for mavorixafor, total infection score for mavorixafor; and a number of quality-of-life measurements and other exploratory endpoints.

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Item 1A. Risk Factors

Risk Factors — what could go wrong, per management

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Biggest changeIf we are found or alleged to have improperly promoted off-label uses, we may become subject to significant liability. • A breakthrough therapy designation or Fast Track designation by the FDA for our product candidates may not lead to a faster development or regulatory review or approval process, and neither of these designations increases the likelihood that our product candidates will receive marketing approval. • If, in the future, we are unable to establish sales and marketing capabilities or to selectively enter into agreements with third parties to sell and market our product candidates, we may not be successful in commercializing our product candidates if and when they are approved. • Even if we obtain and maintain approval for our product candidates from the FDA, we may never obtain approval for our product candidates outside of the United States, which would limit our market opportunities and could harm our business. • Even if we are able to commercialize mavorixafor or any other product candidate that we develop, the product may become subject to unfavorable pricing regulations, third-party reimbursement practices or healthcare reform initiatives, which would harm our business. • We have no experience manufacturing our product candidates on a large clinical or commercial scale and have no manufacturing facility.
Biggest changeIf we are found or alleged to have improperly promoted off-label uses, we may become subject to significant liability. • Our commercial products may become subject to unfavorable pricing regulations, third-party reimbursement practices or healthcare reform initiatives, which would harm our business. • We have limited experience manufacturing our product candidates on a large clinical or commercial scale and have no manufacturing facility.
We have funded our operations to date primarily with proceeds from sales of common stock, warrants and prefunded warrants for the purchase of our preferred stock and our common stock, sales of preferred stock, proceeds from the issuance of convertible debt and borrowings under loan and security agreements.
To date, we have funded our operations to date primarily with proceeds from sales of common stock, warrants, and prefunded warrants for the purchase of our preferred stock and our common stock, sales of preferred stock, proceeds from the issuance of convertible debt, and borrowings under loan and security agreements.
If the FDA or similar regulatory authorities outside of the United States do not approve these other drugs or revoke their approval, or if safety, efficacy, manufacturing or supply issues arise with, the drugs that we choose to evaluate in combination with mavorixafor or any product candidate we develop, we may be unable to obtain approval of or market mavorixafor or any other product candidate we develop.
If the FDA or similar regulatory authorities outside of the United States do not approve these other drugs or revoke their approval of, or if safety, efficacy, manufacturing or supply issues arise with, the drugs that we choose to evaluate in combination with mavorixafor or any product candidate we develop, we may be unable to obtain approval of or market mavorixafor or any product candidate we develop.
If disputes over intellectual property that we have licensed prevent or impair our ability to maintain any of our license agreements on acceptable terms, we may be unable to successfully develop and commercialize the affected product candidates and technologies. The results of clinical trials may not support our product candidate claims.
If disputes over intellectual property that we have licensed prevent or impair our ability to maintain any of our license agreements on acceptable terms, we may be unable to successfully develop and commercialize the affected product or product candidates and technologies. The results of clinical trials may not support our product candidate claims.
If we, our product candidates or the manufacturing facilities for our product candidates fail to comply with cGMPs and other applicable regulatory requirements, the FDA may, among other things: • issue warning letters; • request modifications to promotional materials or require us to provide corrective information to healthcare practitioners; • require us to enter into a consent decree, which can include imposition of various fines, reimbursements for inspection costs, required due dates for specific actions and penalties for noncompliance; • seek an injunction or impose civil or criminal penalties or monetary fines; • suspend or withdraw regulatory approval; • suspend any ongoing clinical trials; • refuse to approve pending applications or supplements to applications filed by us; • suspend or impose restrictions on operations, including costly new manufacturing requirements; or • seize or detain products, refuse to permit the import or export of products, or require us to initiate a product recall.
If we, our product or product candidates or the manufacturing facilities for our product or product candidates fail to comply with cGMPs and other applicable regulatory requirements, the FDA may, among other things: • issue warning letters; • request modifications to promotional materials or require us to provide corrective information to healthcare practitioners; • require us to enter into a consent decree, which can include imposition of various fines, reimbursements for inspection costs, required due dates for specific actions and penalties for noncompliance; • seek an injunction or impose civil or criminal penalties or monetary fines; • suspend or withdraw regulatory approval; • suspend any ongoing clinical trials; • refuse to approve pending applications or supplements to applications filed by us; • suspend or impose restrictions on operations, including costly new manufacturing requirements; or • seize or detain products, refuse to permit the import or export of products, or require us to initiate a product recall.
In addition, we may not be successful in entering into arrangements with third parties to sell and market our product candidates or may be unable to do so on terms that are favorable to us.
In addition, we may not be successful in entering into arrangements with third parties to sell and market our product or product candidates or may be unable to do so on terms that are favorable to us.
Reliance on third-party manufacturers entails risks to which we would not be subject if we manufactured our product candidates ourselves, including reliance on the third party for regulatory compliance and quality assurance, the possibility of breach of the manufacturing agreement by the third party because of factors beyond our control (including a failure to synthesize and manufacture our product candidates or any products that we may eventually commercialize in accordance with our specifications), and the possibility of termination or nonrenewal of the agreement by the third party, based on its own business priorities, at a time that is costly or damaging to us.
Reliance on third-party manufacturers entails risks to which we would not be subject if we manufactured our product or product candidates ourselves, including reliance on the third party for regulatory compliance and quality assurance, the possibility of breach of the manufacturing agreement by the third party because of factors beyond our control (including a failure to synthesize and manufacture our product candidates or any products that we may eventually commercialize in accordance with our specifications), and the possibility of termination or nonrenewal of the agreement by the third party, based on its own business priorities, at a time that is costly or damaging to us.
Our current manufacturers and any future manufacturers may not be able to manufacture our product candidates at a cost or in quantities or in a timely manner necessary to make commercially successful products. If we successfully commercialize any of our product candidates, we may be required to establish large-scale commercial manufacturing capabilities.
Our current manufacturers and any future manufacturers may not be able to manufacture our product or product candidates at a cost or in quantities or in a timely manner necessary to make commercially successful products. If we successfully commercialize any of our product candidates, we may be required to establish large-scale commercial manufacturing capabilities.
Any significant delay in the supply of a product candidate or its key materials for an ongoing clinical study could considerably delay completion of our clinical studies, product testing and potential regulatory approval of our product candidates.
Any significant delay in the supply of a product or product candidate or its key materials for an ongoing clinical study could considerably delay completion of our clinical studies, product testing and potential regulatory approval of our product candidates.
Furthermore, because of the substantial amount of discovery required in connection with intellectual property litigation, there is a risk that some of our confidential information could be compromised by disclosure during this type of litigation.
Furthermore, because of the substantial amount of discovery required in connection with intellectual property litigation, there is a risk that some of our confidential information could be compromised by disclosure during this type of litigation.
Some of the factors that may cause the market price of our common stock to fluctuate include: 62 • our ability or the ability of our collaborators to develop product candidates and conduct clinical trials that demonstrate such product candidates are safe and effective; • our ability or the ability of our collaborators to obtain regulatory approvals for product candidates, and delays or failures to obtain such approvals; • failure of any our product candidates to demonstrate safety and efficacy, receive regulatory approval and achieve commercial success; • failure to maintain our existing third-party license, manufacturing and supply agreements; • failure by us or our licensors to prosecute, maintain or enforce our intellectual property rights; • changes in laws or regulations applicable to our current or future product candidates; • any inability to obtain adequate supply of product candidates or the inability to do so at acceptable prices; • adverse decisions by regulatory authorities; • introduction of new or competing products by our competitors; • failure to meet or exceed financial and development projections that we may provide to the public; • the perception of the pharmaceutical industry by the public, legislatures, regulators and the investment community; • announcements of significant acquisitions, strategic collaborations, joint ventures or capital commitments by us or our competitors; • disputes or other developments relating to proprietary rights, including patents, litigation matters and our ability to obtain intellectual property protection for our technologies; • additions or departures of key personnel; • significant lawsuits, including intellectual property or stockholder litigation; • announcements by us of material developments in our business, financial condition and/or operations; • if securities or industry analysts do not publish research or reports about us, or if they issue an adverse or misleading opinions regarding our business and stock; • changes in the market valuations of similar companies; • general macroeconomic, political and market conditions and overall fluctuations in the financial markets in the United States and abroad; • sales of our common stock or our stockholders in the future; • trading volume of our common stock; • adverse publicity relating to our markets generally, including with respect to other products and potential products in such markets; • changes in the structure of health care payment systems; • period-to-period fluctuations in our financial results; and • the other factors described in this “Risk Factors” section and elsewhere in this Annual Report In addition, companies trading in the stock market in general have experienced extreme price and volume fluctuations that have often been unrelated or disproportionate to the operating performance of these companies, which has resulted in decreased stock prices for many companies notwithstanding the lack of a fundamental change in their underlying business models or prospects.
Some of the factors that may cause the market price of our common stock to fluctuate include: • our ability or the ability of our collaborators to develop product candidates and conduct clinical trials that demonstrate such product candidates are safe and effective; • our ability or the ability of our collaborators to obtain regulatory approvals for product candidates, and delays or failures to obtain such approvals; • failure of any our product candidates to demonstrate safety and efficacy, receive regulatory approval and achieve commercial success; • failure to maintain our existing third-party license, manufacturing and supply agreements; • failure by us or our licensors to prosecute, maintain or enforce our intellectual property rights; • changes in laws or regulations applicable to our current or future product candidates; • any inability to obtain adequate supply of product candidates or the inability to do so at acceptable prices; • adverse decisions by regulatory authorities; • introduction of new or competing products by our competitors; • failure to meet or exceed financial and development projections that we may provide to the public; • the perception of the pharmaceutical industry by the public, legislatures, regulators and the investment community; • announcements of significant acquisitions, strategic collaborations, joint ventures or capital commitments by us or our competitors; • disputes or other developments relating to proprietary rights, including patents, litigation matters and our ability to obtain intellectual property protection for our technologies; • additions or departures of key personnel; • significant lawsuits, including intellectual property or stockholder litigation; • announcements by us of material developments in our business, financial condition and/or operations; • if securities or industry analysts do not publish research or reports about us, or if they issue an adverse or misleading opinions regarding our business and stock; • changes in the market valuations of similar companies; • general macroeconomic, political and market conditions and overall fluctuations in the financial markets in the United States and abroad; • sales of our common stock or our stockholders in the future; • trading volume of our common stock; • adverse publicity relating to our markets generally, including with respect to other products and potential products in such markets; • changes in the structure of health care payment systems; • period-to-period fluctuations in our financial results; and • the other factors described in this “Risk Factors” section and elsewhere in this Annual Report In addition, companies trading in the stock market in general have experienced extreme price and volume fluctuations that have often been unrelated or disproportionate to the operating performance of these companies, which has resulted in decreased stock prices for many companies notwithstanding the lack of a fundamental change in their underlying business models or prospects.
Collaborations involving our product candidates pose many risks to us, including that: • collaborators have significant discretion in determining the efforts and resources that they will apply to these collaborations; • collaborators may not pursue development and commercialization of our product candidates or may elect not to continue or renew development or commercialization programs based on clinical trial results, changes in the collaborator’s strategic focus or available funding or external factors such as an acquisition that diverts resources or creates competing priorities; 52 • collaborators may delay clinical trials, provide insufficient funding for a clinical trial program, stop a clinical trial or abandon a product candidate, repeat or conduct new clinical trials or require a new formulation of a product candidate for clinical testing; • collaborators could independently develop, or develop with third parties, products that compete directly or indirectly with our product candidates or products if the collaborators believe that competitive products are more likely to be successfully developed or can be commercialized under terms that are more economically attractive than ours; • collaborators with marketing and distribution rights to one or more product candidates or products may not commit sufficient resources to the marketing and distribution of such drugs; • collaborators may not properly maintain or defend our intellectual property rights or may use our proprietary information in such a way as to invite litigation that could jeopardize or invalidate our proprietary information or expose us to potential litigation; • disputes may arise between the collaborators and us that result in the delay or termination of the research, development or commercialization of our product candidates or products or that result in costly litigation or arbitration that diverts management attention and resources; • we may lose certain valuable rights under circumstances identified in our collaborations if we undergo a change of control; • collaborations may be terminated and, if terminated, may result in a need for additional capital to pursue further development or commercialization of the applicable product candidates; and • collaboration agreements may not lead to development or commercialization of product candidates in the most efficient manner or at all.
Collaborations involving our product candidates pose many risks to us, including that: • collaborators have significant discretion in determining the efforts and resources that they will apply to these collaborations; • collaborators may not pursue development and commercialization of our product candidates or may elect not to continue or renew development or commercialization programs based on clinical trial results, changes in the collaborator’s strategic focus or available funding or external factors such as an acquisition that diverts resources or creates competing priorities; • collaborators may delay clinical trials, provide insufficient funding for a clinical trial program, stop a clinical trial or abandon a product candidate, repeat or conduct new clinical trials or require a new formulation of a product candidate for clinical testing; • collaborators could independently develop, or develop with third parties, products that compete directly or indirectly with our product candidates or products if the collaborators believe that competitive products are more likely to be successfully developed or can be commercialized under terms that are more economically attractive than ours; • collaborators with marketing and distribution rights to one or more product candidates or products may not commit sufficient resources to the marketing and distribution of such drugs; • collaborators may not properly maintain or defend our intellectual property rights or may use our proprietary information in such a way as to invite litigation that could jeopardize or invalidate our proprietary information or expose us to potential litigation; • disputes may arise between the collaborators and us that result in the delay or termination of the research, development or commercialization of our product candidates or products or that result in costly litigation or arbitration that diverts management attention and resources; • we may lose certain valuable rights under circumstances identified in our collaborations if we undergo a change of control; • collaborations may be terminated and, if terminated, may result in a need for additional capital to pursue further development or commercialization of the applicable product candidates; and • collaboration agreements may not lead to development or commercialization of products or product candidates in the most efficient manner or at all.
If we seek approval of our product candidates outside of the United States, we expect that we will be subject to additional risks in commercialization including: • different regulatory requirements for approval of therapies in foreign countries; • reduced protection for intellectual property rights; • unexpected changes in tariffs, trade barriers and regulatory requirements; • economic weakness, including inflation, or political instability in particular foreign economies and markets; • compliance with tax, employment, immigration and labor laws for employees living or traveling abroad; 46 • foreign currency fluctuations, which could result in increased operating expenses and reduced revenues, and other obligations incident to doing business in another country; • foreign reimbursement, pricing and insurance regimes; • workforce uncertainty in countries where labor unrest is more common than in the United States; • production shortages resulting from any events affecting raw material supply or manufacturing capabilities abroad; and • business interruptions resulting from geopolitical actions, including war and terrorism, or natural disasters and public health epidemics.
If we seek approval of our product candidates outside of the United States, we expect that we will be subject to additional risks in commercialization including: • different regulatory requirements for approval of therapies in foreign countries; • reduced protection for intellectual property rights; • unexpected changes in tariffs, trade barriers and regulatory requirements; • economic weakness, including inflation, or political instability in particular foreign economies and markets; • compliance with tax, employment, immigration and labor laws for employees living or traveling abroad; • foreign currency fluctuations, which could result in increased operating expenses and reduced revenues, and other obligations incident to doing business in another country; • foreign reimbursement, pricing and insurance regimes; • workforce uncertainty in countries where labor unrest is more common than in the United States; • production shortages resulting from any events affecting raw material supply or manufacturing capabilities abroad; and • business interruptions resulting from geopolitical actions, including war and terrorism, or natural disasters and public health epidemics.
Before obtaining regulatory approvals for the commercial sale of any product candidate, we must successfully meet a number of critical developmental milestones, including: • developing dosages that will be well-tolerated, safe and effective; • completing the development and scale-up to permit manufacture of our product candidates in commercial quantities and at acceptable costs; • demonstrating through pivotal clinical trials that each product candidate is safe and effective in patients for the intended indication; • establishing commercial manufacturing capabilities or making arrangements with third-party manufacturers; and • obtaining and maintaining patent and trade secret protection and non-patent exclusivity for our product candidates.
Before obtaining regulatory approvals for the commercial sale of any product candidate, we must successfully meet a number of critical developmental milestones, including: 34 • developing dosages that will be well-tolerated, safe and effective; • completing the development and scale-up to permit manufacture of our product candidates in commercial quantities and at acceptable costs; • demonstrating through pivotal clinical trials that each product candidate is safe and effective in patients for the intended indication; • establishing commercial manufacturing capabilities or making arrangements with third-party manufacturers; and • obtaining and maintaining patent and trade secret protection and non-patent exclusivity for our product candidates.
While physicians in the United States may choose, and are generally permitted, to prescribe products for uses that are not described in the product’s labeling and for uses that differ from those tested in clinical trials and approved by the regulatory authorities, our ability to promote any of our products candidates, if approved, will be limited to those indications and populations that are specifically approved by the FDA or such other regulatory agencies, and if we are found to have promoted such off-label uses, we may become subject to significant liability.
While physicians in the United States may choose, and are generally permitted, to prescribe products for uses that are not described in the product’s labeling and for uses that differ from those tested in clinical trials and approved by the regulatory authorities, our ability to promote any of our products will be limited to those indications and populations that are specifically approved by the FDA or such other regulatory agencies, and if we are found to have promoted such off-label uses, we may become subject to significant liability.
Regardless of merit or eventual outcome, liability claims may result in: • reduced resources of our management to pursue our business strategy; • decreased demand for any products that we may develop; • injury to our reputation and significant negative media attention; • withdrawal of clinical trial participants; • significant costs to defend any related litigation; • substantial monetary awards to trial participants or patients; • loss of revenue; • increased insurance costs; and • the inability to commercialize any products that we may develop.
Regardless of merit or eventual outcome, liability claims may result in: • reduced resources of our management to pursue our business strategy; • decreased demand for any products that we may develop; • injury to our reputation and significant negative media attention; 45 • withdrawal of clinical trial participants; • significant costs to defend any related litigation; • substantial monetary awards to trial participants or patients; • loss of revenue; • increased insurance costs; and • the inability to commercialize any products that we may develop.
If we are found or alleged to have improperly promoted off-label uses, we may become subject to significant liability. 42 The FDA and other regulatory agencies strictly regulate the promotional claims that may be made about drug products. These regulations include standards and restrictions for direct-to-consumer advertising, industry-sponsored scientific and educational activities, promotional activities involving the internet and off-label promotion.
If we are found or alleged to have improperly promoted off-label uses, we may become subject to significant liability. The FDA and other regulatory agencies strictly regulate the promotional claims that may be made about drug products. These regulations include standards and restrictions for direct-to-consumer advertising, industry-sponsored scientific and educational activities, promotional activities involving the internet and off-label promotion.
We are unable to predict the timing or 34 amount of increased expenses, or when or if we will be able to achieve or maintain profitability, and such expense could increase beyond our expectations if the FDA or any other regulatory agency requires such additional clinical trials or nonclinical studies as part of the application and approval process or post-approval process if we are successful at achieving regulatory approval.
We are unable to predict the timing or amount of increased expenses, or when or if we will be able to achieve or maintain profitability, and such expense could increase beyond our expectations if the FDA or any other regulatory agency requires such additional clinical trials or nonclinical studies as part of the application and approval process or post-approval process if we are successful at achieving regulatory approval.
Market acceptance of any of our product candidates for which we receive approval depends on a number of factors, including: • the efficacy and safety of such product candidates as demonstrated in clinical trials; • the clinical indications for which the product candidate is approved; • acceptance by hospitals, physicians and patients of the product candidate as a safe and effective treatment, particularly the ability of mavorixafor and our other product candidates to establish themselves as a new standard of care for the indications that we are pursuing; • the potential and perceived advantages of our product candidates over alternative treatments as compared to the relative costs of the product candidates and alternative treatments; • the prevalence and severity of any side effects with respect to our product candidates, including mavorixafor; • our ability to offer any approved products for sale at competitive prices; • the timing of market introduction of our products as well as competitive products; • our pricing, and the availability of coverage and adequate reimbursement by third party payors and government authorities; • relative convenience and ease of administration; and • the effectiveness of our sales and marketing efforts and those of our potential future collaborators.
Market acceptance of any of our approved product or product candidates for which we receive approval in the future depends on a number of factors, including: • the efficacy and safety of such product candidates as demonstrated in clinical trials; • the clinical indications for which the product candidate is approved; • acceptance by hospitals, physicians and patients of the product candidate as a safe and effective treatment, particularly the ability of mavorixafor and our other product candidates to establish themselves as a new standard of care for the indications that we are pursuing; • the potential and perceived advantages of our products and product candidates over alternative treatments as compared to their relative costs; • the prevalence and severity of any side effects with respect to our products or product candidates, including mavorixafor; • our ability to offer any approved products for sale at competitive prices; • the timing of market introduction of our products as well as competitive products; • our pricing, and the availability of coverage and adequate reimbursement by third party payors and government authorities; • relative convenience and ease of administration; and • the effectiveness of our sales and marketing efforts and those of our potential future collaborators.
Even if patents covering our product candidates are obtained, once the patent life has expired, we may be open to competition from competitive products, including generics or biosimilars. Given the amount of time required for the development, testing and regulatory review of new product candidates, patents protecting such candidates might expire before or shortly after such candidates are commercialized.
Even if patents covering our product candidates are obtained, once the patent life has expired, we may be open to competition from competitive products, including generics or biosimilars. Given the amount of time 52 required for the development, testing and regulatory review of new product candidates, patents protecting such candidates might expire before or shortly after such candidates are commercialized.
In addition, any drug-related side effects could affect patient recruitment or the ability of enrolled patients to complete the trial or result in potential product liability claims. Any 39 of these occurrences may harm our business, financial condition and prospects significantly. Further, clinical trials by their nature utilize a sample of the potential patient population.
In addition, any drug-related side effects could affect patient recruitment or the ability of enrolled patients to complete the trial or result in potential product liability claims. Any of these occurrences may harm our business, financial condition and prospects significantly. Further, clinical trials by their nature utilize a sample of the potential patient population.
In any of the foregoing or in other situations involving third-party intellectual 53 property rights, if we are unsuccessful in defending against claims of patent infringement, we could be forced to pay damages or be subjected to an injunction that would prevent us from utilizing the patented subject matter. Such outcomes could harm our business.
In any of the foregoing or in other situations involving third-party intellectual property rights, if we are unsuccessful in defending against claims of patent infringement, we could be forced to pay damages or be subjected to an injunction that would prevent us from utilizing the patented subject matter. Such outcomes could harm our business.
We will require additional capital to sustain our operations, and to carry out our business plans, which may include raising funds through public or private equity or debt financings, third-party funding, marketing and distribution arrangements, as well as other collaborations, strategic alliances and licensing arrangements, or any combination of these approaches.
We will require additional capital to sustain our operations, and to carry out our business plans thereafter, which may include raising funds through public or private equity or debt financings, third-party funding, marketing and distribution arrangements, as well as other collaborations, strategic alliances and licensing arrangements, or any combination of these approaches.
We also could be required to: • seek new or additional collaborators for one or more of our current or future product candidates at an earlier stage than otherwise would be desirable or on terms that are less favorable than might otherwise be available; or • relinquish or license on unfavorable terms our rights to technologies or product candidates that we otherwise would seek to develop or commercialize ourselves.
We also could be required to: • seek new or additional collaborators for one or more of our current or future product candidates at an earlier stage than otherwise would be desirable or on terms that are less favorable than might otherwise be available; or 31 • relinquish or license on unfavorable terms our rights to technologies or product candidates that we otherwise would seek to develop or commercialize ourselves.
We are also subject to other laws and regulations governing our international operations, including regulations administered by the U.S. government and authorities in the European Union or the United Kingdom, including applicable export control 49 regulations, economic sanctions on countries and persons, customs requirements and currency exchange regulations, which we collectively refer to as Trade Control Laws.
We are also subject to other laws and regulations governing our international operations, including regulations administered by the U.S. government and authorities in the European Union or the United Kingdom, including applicable export control regulations, economic sanctions on countries and persons, customs requirements and currency exchange regulations, which we collectively refer to as Trade Control Laws.
We are not aware of any threatened or pending claims related to these matters or concerning the agreements with our senior management, but in the future litigation may be necessary to defend against such claims. If we fail in defending any such claims, in addition to paying monetary damages, we may lose valuable intellectual property rights or personnel.
We are not aware of any threatened or pending claims related to these matters or concerning the agreements with our senior management, but in the future 55 litigation may be necessary to defend against such claims. If we fail in defending any such claims, in addition to paying monetary damages, we may lose valuable intellectual property rights or personnel.
If we are unable to raise additional funds through equity or debt financings or through licensing, collaboration or similar arrangements when needed, we may be required to delay, limit, reduce or terminate our product development or future commercialization efforts or grant rights to develop and market product candidates that we would otherwise prefer to develop and market ourselves.
If we are unable to raise additional funds through equity or debt financings or through licensing, collaboration or similar arrangements when needed, we may be required to delay, limit, reduce, restructure or terminate our product development or future commercialization efforts or grant rights to develop and market product candidates that we would otherwise prefer to develop and market ourselves.
Although our management team has previous experience with such efforts, there can be no assurance that we will be successful in building these operations. If we are unable to establish adequate sales, marketing and distribution capabilities, we may not be able to generate product revenue and may not become profitable.
Although our management team has previous experience with such efforts, there can be no assurance that we will be successful in building these operations. If we are unable to establish and maintain adequate sales, marketing and distribution capabilities, we may not be able to generate product revenue and may not become profitable.
Our employees, principal investigators, CROs, CMOs and consultants may engage in misconduct or other improper activities, 51 including noncompliance with regulatory standards and requirements, which could have a material adverse effect on our business. We are exposed to the risk that our employees, principal investigators, CROs, CMOs and consultants may engage in fraudulent conduct or other illegal activity.
Our employees, principal investigators, CROs, CMOs and consultants may engage in misconduct or other improper activities, including noncompliance with regulatory standards and requirements, which could have a material adverse effect on our business. We are exposed to the risk that our employees, principal investigators, CROs, CMOs and consultants may engage in fraudulent conduct or other illegal activity.
If these in-licenses are terminated, or if the underlying patents fail to provide the intended exclusivity, competitors or other third parties may gain the freedom to seek regulatory approval of, and to market, products identical to ours and we may be required to cease our development and commercialization of our product candidates.
If these in-licenses are terminated, or if the underlying patents fail to provide the intended exclusivity, competitors or other third parties may gain the freedom to seek regulatory approval of, and to market, products identical to ours and we may be 53 required to cease our development and commercialization of our product candidates.
To the extent that we raise additional capital through the sale of equity or convertible debt securities, your ownership interest will be diluted, and the terms of these securities may include liquidation or other preferences that adversely affect your rights as a holder of our common stock.
To the extent that we raise additional capital through the sale of equity or convertible debt securities, your ownership interest will be diluted, and the terms of 32 these securities may include liquidation or other preferences that adversely affect your rights as a holder of our common stock.
If a regulatory agency discovers previously unknown problems with a product, such as adverse events of unanticipated severity or frequency, or problems with the facility where the product is manufactured, a regulatory agency may impose restrictions on that product, the manufacturing facility or us, including requiring recall or withdrawal of the product from the market or suspension of manufacturing.
If a regulatory agency discovers previously unknown problems with our product, such as adverse events of unanticipated severity or frequency, or problems with the facility where the product is manufactured, a regulatory agency may impose restrictions on that product, the manufacturing facility or us, including requiring recall or withdrawal of the product from the market or suspension of manufacturing.
With respect to patent rights, we do not know whether any of the pending patent applications for any of our product candidates will result in the issuance of patents that protect our technology or products, or which will effectively prevent others from commercializing competitive technologies and products.
With respect to patent rights, we do not know whether any of the pending patent applications for any of our products or product candidates will result in the issuance of patents that protect our technology or products, or which will effectively prevent others 51 from commercializing competitive technologies and products.
We cannot predict what healthcare reform initiatives may be adopted in the future. However, we expect that 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 will receive for any approved product.
We cannot predict what healthcare reform initiatives may be adopted in the future. However, we expect that 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.
Increased inflation rates can adversely affect us by increasing our costs, including labor and employee benefit costs. 61 Risks Related to Ownership of Our Common Stock We are currently not in compliance with the Nasdaq continued listing requirements.
Increased inflation rates can adversely affect us by increasing our costs, including labor and employee benefit costs. Risks Related to Ownership of Our Common Stock We are currently not in compliance with the Nasdaq continued listing requirements.
We may encounter unforeseen expenses, difficulties, complications, delays and other unknown factors that may adversely affect our business. The size of our future net losses will depend, in part, on the rate of future growth of our expenses and our ability to generate revenues.
We may encounter unforeseen expenses, difficulties, complications, delays, and/or other unknown factors that may adversely affect our business. The size of our future net losses will depend, in part, on the rate of future growth of our expenses and our ability to generate revenues.
Proceedings to enforce our patent rights in foreign jurisdictions could result in substantial cost and divert our efforts and attention from other aspects of our business. 58 As another example, the complexity and uncertainty of European patent laws have increased in recent years.
Proceedings to enforce our patent rights in foreign jurisdictions could result in substantial cost and divert our efforts and attention from other aspects of our business. As another example, the complexity and uncertainty of European patent laws have increased in recent years.
Such litigation or proceedings could substantially increase our operating losses and reduce the resources available for development activities or any future sales, marketing or distribution activities. 57 We may not have sufficient financial or other resources to adequately conduct such litigation or proceedings.
Such litigation or proceedings could substantially increase our operating losses and reduce the resources available for development activities or any future sales, marketing or distribution activities. We may not have sufficient financial or other resources to adequately conduct such litigation or proceedings.
Under the Tax Act, as modified by the CARES 60 Act, our federal NOLs generated in tax years ending after December 31, 2017 may be carried forward indefinitely, but the deductibility of federal NOLs, particularly for tax years beginning after December 31, 2020, may be limited.
Under the Tax Act, as modified by the CARES Act, our federal NOLs generated in tax years ending after December 31, 2017 may be carried forward indefinitely, but the deductibility of federal NOLs, particularly for tax years beginning after December 31, 2020, may be limited.
Our ability to generate revenue and become profitable depends upon our ability to successfully obtain marketing approval and commercialize our product candidates, including mavorixafor, or other product candidates that we may develop, in-license or acquire in the future.
Our ability to generate revenue and become profitable depends upon our ability to successfully commercialize XOLREMDI and to obtain marketing approval and commercialize our product candidates, including mavorixafor, or other product candidates that we may develop, in-license or acquire in the future.
Clinical data are often susceptible to varying interpretations and analyses, and many companies that have believed their product candidates performed satisfactorily in 38 clinical trials have nonetheless failed to receive marketing approval of their product candidates.
Clinical data are often susceptible to varying interpretations and analyses, and many companies that have believed their product candidates performed satisfactorily in clinical trials have nonetheless failed to receive marketing approval of their product candidates.
In addition, any testing by us, as and when required, conducted in connection with Section 404, or any subsequent testing by our independent registered public accounting firm, as and when required, may reveal deficiencies in our internal control over financial reporting that are deemed to be significant deficiencies or material weaknesses or that may require prospective or retroactive changes to our 64 consolidated financial statements or identify other areas for further attention or improvement.
In addition, any testing by us, as and when required, conducted in connection with Section 404, or any subsequent testing by our independent registered public accounting firm, as and when required, may reveal deficiencies in our internal control over financial reporting that are deemed to be significant deficiencies or material weaknesses or that may require prospective or retroactive changes to our 61 consolidated financial statements or identify other areas for further attention or improvement.
If the FDA or comparable foreign regulatory authorities become aware of new safety information after approval of any of our product candidates, these regulatory authorities may require labeling changes or the FDA may require establishment of a Risk Evaluation Mitigation Strategy (“REMS”), or similar strategy, impose significant restrictions on a product’s indicated uses or marketing, impose ongoing requirements for potentially costly post-approval studies or post-market surveillance.
If the FDA or comparable foreign regulatory authorities become aware of new safety information after approval of any of our product candidates, these regulatory authorities may require labeling changes or the FDA may require establishment of a Risk Evaluation Mitigation Strategy (“REMS”), impose significant restrictions on our product’s indicated uses or marketing, or impose ongoing requirements for potentially costly post-approval 40 studies or post-market surveillance.
Additionally, any product candidate for which we obtain marketing approval could be subject to marketing restrictions or withdrawal from the market and we may be subject to penalties if we fail to comply with regulatory requirements or if we experience unanticipated problems with our products. • The FDA and other regulatory agencies actively enforce the laws and regulations prohibiting the promotion of off-label uses.
Additionally, any product candidate for which we obtain marketing approval could be subject to marketing restrictions or withdrawal from the market and we may be subject to penalties if we fail to comply with regulatory requirements or if we experience unanticipated problems with our products. • The FDA and other domestic and foreign regulatory agencies actively enforce the laws and regulations prohibiting the promotion of off-label uses.
Current and future legislation may increase the difficulty and cost for us to obtain marketing approval of and commercialize our product candidates and affect the prices we may obtain.
Current and future legislation may increase the difficulty and cost for us to obtain marketing approval of and commercialize our product or product candidates and affect the prices we may obtain.
See the sections of this Annual Report on Form 10-K for the fiscal year ended December 31, 2023 entitled, “Business – Government Regulation – Pharmaceutical Coverage, Pricing and Reimbursement” and “Business – Government Regulation – Healthcare Reform.” We are subject to anti-corruption laws, as well as export control laws, customs laws, sanctions laws and other laws governing our operations.
See the sections of this Annual Report on Form 10-K for the fiscal year ended December 31, 2024 entitled, “Business – Government Regulation – Pharmaceutical Coverage, Pricing and Reimbursement” and “Business – Government Regulation – Healthcare Reform.” We are subject to anti-corruption laws, as well as export control laws, customs laws, sanctions laws and other laws governing our operations.
Such litigation, if instituted, could result in substantial costs and diversion of management attention and resources, which could significantly harm our business, financial condition, results of operations and reputation. 63 “Penny stock” rules may make buying or selling our securities difficult which may make our stock less liquid and make it harder for investors to buy and sell our securities.
Such litigation, if instituted, could result in substantial costs and diversion of management attention and resources, which could significantly harm our business, financial condition, results of operations and reputation. 60 “Penny stock” rules may make buying or selling our securities difficult which may make our stock less liquid and make it harder for investors to buy and sell our securities.
In the United States and some foreign jurisdictions, there have been a number of legislative and regulatory changes and proposed changes regarding the healthcare system that could prevent or delay marketing approval of our product candidates, restrict post-approval activities and affect our ability to sell profitably any product candidates for which we obtain marketing approval.
In the United States and some foreign jurisdictions, there have been a number of legislative and regulatory changes and proposed changes regarding the healthcare system that could prevent or delay marketing approval of product candidates, restrict post-approval activities and affect our ability to sell profitably any approved product or product candidates for which we obtain marketing approval in the future.
If our product candidates receive marketing approval and we or others identify undesirable side effects caused by such product candidates (or any other similar drugs) after such approval, a number of potentially significant negative consequences could result, including: • regulatory authorities may withdraw or limit their approval of such product candidates; • regulatory authorities may require the addition of labeling statements, such as a “boxed” warning or a contraindication; • we may be required to create a medication guide outlining the risks of such side effects for distribution to patients; • we may be required to change the way such product candidates are distributed or administered, conduct additional clinical trials or change the labeling of the product candidates; • regulatory authorities may require a Risk Evaluation and Mitigation Strategy plan to mitigate risks, which could include medication guides, physician communication plans, or elements to assure safe use, such as restricted distribution methods, patient registries and other risk minimization tools; • we may be subject to regulatory investigations and government enforcement actions; • we may decide to remove such product candidates from the marketplace after they are approved; • we could be sued and held liable for injury caused to individuals exposed to or taking our product candidates; and • our reputation may suffer.
For XOLREMDI and any other product candidates that receive marketing approval in the future, if we or others identify undesirable side effects caused by such product candidates (or any other similar drugs) after such approval, a number of potentially significant negative consequences could result, including: • regulatory authorities may withdraw or limit their approval of such product candidates; • regulatory authorities may require the addition of labeling statements, such as a “boxed” warning or a contraindication; • we may be required to create a medication guide outlining the risks of such side effects for distribution to patients; • we may be required to change the way such product candidates are distributed or administered, conduct additional clinical trials or change the labeling of the product candidates; • regulatory authorities may require a Risk Evaluation and Mitigation Strategy to mitigate risks, which could include medication guides, physician communication plans, or elements to assure safe use, such as restricted distribution methods, patient registries and other risk minimization tools; • we may be subject to regulatory investigations and government enforcement actions; • we may decide to remove such product candidates from the marketplace after they are approved; • we could be sued and held liable for injury caused to individuals exposed to or taking our product candidates; and • our reputation may suffer.
Even if we are able to successfully complete the development and regulatory reviews described above, we anticipate incurring significant costs associated with commercializing these products, if they are approved. Even if we are able to generate revenues from the sale of our product candidates, we may not become profitable and may need to obtain additional funding to continue operations.
Even if we are able to successfully complete the development and regulatory reviews described above, we anticipate incurring significant costs associated with commercializing these products, if they are approved. Even if we are able to generate meaningful revenues from the sale of our product, we may not become profitable and may need to obtain additional funding to continue operations.
As a result, our results of operations and the commercial prospects for our product candidates would be harmed, our costs could increase and our ability to generate revenues could be delayed. Disruptions in our supply chain could delay the commercial launch of our product candidates. Any significant disruption in our supplier relationships could harm our business.
As a result, our results of operations and the commercial prospects for our product candidates would be harmed, our costs could increase and our ability to generate revenues could be delayed. Disruptions in our supply chain could delay the commercial sale of our product. Any significant disruption in our supplier relationships could harm our business.
We expect to continue to incur significant expenses and increasing operating losses for at least the next several years as we conduct additional clinical trials for our product candidates; continue to discover and develop additional product candidates; acquire or in-license other product candidates and technologies; maintain, expand and protect our intellectual property portfolio; hire additional clinical, scientific and commercial personnel; establish a commercial manufacturing source and secure supply chain capacity sufficient to provide commercial quantities of any product candidates for which we may obtain regulatory approval; seek regulatory approvals for any product candidates that successfully complete clinical trials; establish a sales, marketing and distribution infrastructure to commercialize any products for which we may obtain regulatory approval; and add operational, financial and management information systems and personnel, including personnel to support our product development and planned future commercialization efforts.
We expect to continue to incur significant expenses and operating losses for at least the next several years as we conduct additional clinical trials for our product candidates; continue to discover and develop additional product candidates; acquire or in-license other product candidates and technologies; maintain, expand and protect our intellectual property portfolio; hire additional clinical, scientific and commercial personnel; establish a commercial manufacturing source and secure supply chain capacity sufficient to provide commercial quantities of any product candidates for which we may obtain regulatory approval; seek regulatory approvals for any product candidates that successfully complete clinical trials; further grow a sales, marketing and distribution infrastructure to commercialize XOLREMDI and any other products for which we may obtain regulatory approval; and add operational, financial and management information systems and personnel, including personnel to support our product 29 development and planned future commercialization efforts.
The regulatory review and approval processes of the FDA and comparable foreign regulatory authorities are lengthy, time-consuming and inherently unpredictable, and if we are ultimately unable to obtain regulatory approval for our product candidates, including mavorixafor, our business will be substantially harmed.
The regulatory review and approval processes of the FDA and comparable foreign regulatory authorities are lengthy, time-consuming and inherently unpredictable, and if we are ultimately unable to obtain regulatory approval for our product candidates, including additional indications for mavorixafor, our business will be substantially harmed.
Inadequate funding for the FDA, the SEC and other government agencies could hinder their ability to hire and retain key leadership and other personnel, prevent new products and services from being developed or commercialized in a timely manner or otherwise prevent those agencies from performing normal business functions on which the operation of our business may rely, which could negatively impact our business.
Inadequate funding for the FDA, the SEC and other government agencies could hinder their ability to hire and retain key personnel, and substantial leadership, personnel, and policy changes could prevent new products and services from being developed or commercialized in a timely manner or otherwise prevent those agencies from performing normal business functions on which the operation of our business may rely, which could negatively impact our business.
We are a “smaller reporting company” and cannot predict if the reduced reporting requirements applicable to smaller reporting companies will make our securities less attractive to investors. We are a “smaller reporting company” under the Exchange Act as of June 30, 2023.
We are a “smaller reporting company” and cannot predict if the reduced reporting requirements applicable to smaller reporting companies will make our securities less attractive to investors. We are a “smaller reporting company” under the Exchange Act as of June 30, 2024.
Clinical trials may be delayed, suspended or terminated for a variety of reasons, including the following: • delay or failure in reaching agreement with the FDA or a comparable foreign regulatory authority on a trial design that we are able to execute; • delay or failure in obtaining authorization to commence a trial or inability to comply with conditions imposed by a regulatory authority regarding the scope or design of a clinical trial; • inability, delay or failure in identifying and maintaining a sufficient number of trial sites, many of which may already be engaged in competing clinical trial programs; • delay or failure in recruiting and enrolling suitable subjects to participate in a trial; • delay or failure in having subjects complete a trial or return for post-treatment follow-up; • clinical sites and investigators deviating from trial protocol, failing to conduct the trial in accordance with regulatory requirements, or dropping out of a trial; • delay or failure in reaching agreement on acceptable terms with prospective clinical research organizations (“CROs”) and clinical trial sites, the terms of which can be subject to extensive negotiation and may vary significantly among different CROs and trial sites; • delay or failure in obtaining institutional review board (“IRB”) approval to conduct a clinical trial at each site; • delays resulting from negative or equivocal findings of the Data Safety Monitoring Board (“DSMB”) if any; • ambiguous or negative results; • decision by the FDA, a comparable foreign regulatory authority, or recommendation by a DSMB to suspend or terminate clinical trials at any time for safety issues or for any other reason; • inadequate supply of drug product for use in nonclinical studies or clinical trials; • lack of adequate funding to continue the product development program; • external business disruptions affecting the initiation, patient enrollment, development and operation of our clinical trials, including a public health emergency and unforeseen events such as the war in Ukraine; or • changes in governmental regulations or requirements.
Clinical trials may be delayed, suspended or terminated for a variety of reasons, including the following: • delay or failure in reaching agreement with the FDA or a comparable foreign regulatory authority on a trial design that we are able to execute; • delay or failure in obtaining authorization to commence a trial or inability to comply with conditions imposed by a regulatory authority regarding the scope or design of a clinical trial; • inability, delay or failure in identifying and maintaining a sufficient number of trial sites, many of which may already be engaged in competing clinical trial programs; • delay or failure in recruiting and enrolling suitable subjects to participate in a trial; • delay or failure in having subjects complete a trial or return for post-treatment follow-up; • clinical sites and investigators deviating from trial protocol, failing to conduct the trial in accordance with regulatory requirements, or dropping out of a trial; • delay or failure in reaching agreement on acceptable terms with prospective CROs and clinical trial sites, the terms of which can be subject to extensive negotiation and may vary significantly among different CROs and trial sites; • delay or failure in obtaining institutional review board (“IRB”) approval to conduct a clinical trial at each site; • delays resulting from negative or equivocal findings of the Data Safety Monitoring Board (“DSMB”) if any; • ambiguous or negative results; • decision by the FDA, a comparable foreign regulatory authority, or recommendation by a DSMB to suspend or terminate clinical trials at any time for safety issues or for any other reason; • inadequate supply of drug product for use in nonclinical studies or clinical trials; • lack of adequate funding to continue the product development program; • external business disruptions affecting the initiation, patient enrollment, development and operation of our clinical trials, including public health emergencies and geopolitical conflicts such as the war in Ukraine or in Gaza; or • changes in governmental regulations or requirements.
Our ability to generate profits from operations and thereafter to remain profitable depends heavily on: • outcomes and timing of regulatory reviews, approvals and other actions; • our ability to manufacture any approved products on commercially reasonable terms; • our ability to establish a sales and marketing organization or suitable third-party alternatives for any approved product; • the scope, number, progress, duration, endpoints, cost, results and timing of clinical trials and nonclinical studies of our current or potential future product candidates, including in particular the scope, progress, duration, endpoints, cost, results and timing for completion of our Phase 2 clinical trial of mavorixafor for the treatment of chronic neutropenic disorders; • our ability to raise sufficient funds to support the development and potential commercialization of our product candidates; • our ability to obtain marketing approval for our product candidates; • our ability to establish and maintain licensing, collaboration or similar arrangements on favorable terms and whether and to what extent we retain development or commercialization responsibilities under any new licensing, collaboration or similar arrangement; • the success of any other business, product or technology that we acquire or in which we invest; • our ability to maintain, expand and defend the scope of our intellectual property portfolio; • the number and characteristics of product candidates and programs that we pursue; • hire additional clinical, regulatory and scientific personnel; and 31 • incur additional legal, accounting and other expenses associated with operating as a public company.
Our ability to generate profits from operations and thereafter to remain profitable depends heavily on: • our ability to generate revenue from XOLREMDI; • outcomes and timing of regulatory reviews, approvals and other actions; • our ability to manufacture any approved products on commercially reasonable terms; • our ability to maintain an effective sales and marketing organization or suitable third-party alternatives for any approved products; • the scope, number, progress, duration, endpoints, cost, results and timing of clinical trials and nonclinical studies of our current or potential future product candidates, including in particular the scope, progress, duration, endpoints, cost, results and timing for completion of our Phase 3 clinical trial of mavorixafor for the treatment of chronic neutropenic disorders; • our ability to raise sufficient funds to support the development and potential commercialization of our product candidates; • our ability to market our approved product and obtain marketing approval for our product candidates; • our ability to establish and maintain licensing, collaboration or similar arrangements on favorable terms and whether and to what extent we retain development or commercialization responsibilities under any new licensing, collaboration or similar arrangement; • the success of any other business, product or technology that we acquire or in which we invest; • our ability to maintain, expand and defend the scope of our intellectual property portfolio; • the number and characteristics of product candidates and programs that we pursue; • hire additional clinical, regulatory and scientific personnel; and • incur additional legal, accounting and other expenses associated with operating as a public company.
We cannot be sure that coverage and reimbursement will be available for mavorixafor or any other product that we commercialize and, if coverage and reimbursement is available, the level of reimbursement. Reimbursement may impact the demand for, or the price of, any product candidate for which we obtain marketing approval.
We cannot be sure that coverage and reimbursement will be available for XOLREMDI or any other product that we commercialize and, if coverage and reimbursement is available, the level of reimbursement. Reimbursement may impact the demand for, or the price of, any product candidate for which we obtain marketing approval.
Information about certain clinical trials, including results (positive or negative) will be made public according to each country’s clinical trial register policies. Competitors may use this publicly available information to gain knowledge regarding the progress of development programs. Product development involves a lengthy and expensive process, with uncertain outcomes.
Information about certain clinical trials, including results (positive or negative) will be made public according to each country’s clinical trial registration policies. Competitors may use this publicly available information to gain knowledge regarding the progress of development programs. 37 Product development involves a lengthy and expensive process, with uncertain outcomes.
See the section in this Annual Report on Form 10-K for the fiscal year ended December 31, 2023 entitled “Business – Government Regulation – Other Healthcare Laws and Compliance Requirements.” Efforts to ensure that our business arrangements with third parties will comply with applicable healthcare laws and regulations will involve substantial costs.
See the section in this Annual Report on Form 10-K for the fiscal year ended December 31, 2024 entitled “Business – Government Regulation – Other Healthcare Laws and Compliance Requirements.” Efforts to ensure that our business arrangements with third parties comply with applicable healthcare laws and regulations involve substantial costs.
We have no experience manufacturing pharmaceutical products on a commercial scale and some of these manufacturers will need to increase their scale of production to meet our projected needs for commercial manufacturing, the satisfaction of which may not be met on a timely basis. We rely on third-party CROs to conduct our preclinical studies and clinical trials.
We have limited experience manufacturing pharmaceutical products on a commercial scale and some of these manufacturers will need to increase their scale of production to meet our projected needs for commercial manufacturing, the satisfaction of which may not be met on a timely basis. 48 We rely on third-party CROs to conduct our preclinical studies and clinical trials.
Successfully completing clinical trials and obtaining approval of an NDA is a complex, lengthy, expensive and uncertain process, and the FDA, or a comparable foreign regulatory authority, may delay, limit or deny approval of mavorixafor for the treatment of WHIM syndrome or other indications for many reasons, including, among others: • disagreement with the design or implementation of our clinical trials; • disagreement with the sufficiency of our clinical trials; • failure to demonstrate the safety and efficacy of mavorixafor or any other product candidate for its proposed indications; • failure to demonstrate that any clinical and other benefits of mavorixafor or any other product candidate outweigh its safety risks; • a negative interpretation of the data from our nonclinical studies or clinical trials; • deficiencies in the manufacturing or control processes or failure of third-party manufacturing facilities with which we contract for clinical and commercial supplies to comply with current cGMPs; • insufficient data collected from clinical trials of mavorixafor or any other product candidate, or changes in the approval requirements that render its nonclinical and clinical data insufficient to support the filing of an NDA or to obtain regulatory approval; or 36 • changes in clinical practice in or approved products available for the treatment of the target patient population that could have an impact on the indications that we are pursuing for mavorixafor or our other product candidates.
Successfully completing clinical trials and obtaining approval of an NDA is a complex, lengthy, expensive and uncertain process, and the FDA, or a comparable foreign regulatory authority, may delay, limit or deny approval of mavorixafor for the treatment of other indications for many reasons, including, among others: • disagreement with the design or implementation and sufficiency of our clinical trials; • failure to demonstrate the safety and efficacy of mavorixafor or any other product candidate for its proposed indications and that; 35 • any clinical and other benefits of mavorixafor or any other product candidate outweigh its safety risks; • deficiencies in the manufacturing or control processes or failure of third-party manufacturing facilities with which we contract for clinical and commercial supplies to comply with current cGMPs; • insufficient data collected from clinical trials of mavorixafor or any other product candidate, or changes in the approval requirements that render its nonclinical and clinical data insufficient to support the filing of an NDA or to obtain regulatory approval; or • changes in clinical practice in or approved products available for the treatment of the target patient population that could have an impact on the indications that we are pursuing for mavorixafor or our other product candidates.
Risks Related to Our Financial Position and Need for Additional Capital We have incurred significant losses and have not generated revenue from product sales since our inception. We expect to continue to incur losses for the foreseeable future and we may never achieve or maintain profitability. We are a late clinical-stage biopharmaceutical company.
Risks Related to Our Financial Position and Need for Additional Capital We have incurred significant losses and have not generated significant revenue from product sales since our inception. We expect to continue to incur losses for the foreseeable future and we may never achieve or maintain profitability. We are a commercial-stage biopharmaceutical company.
Risks Related to Government Regulation Our relationships with customers and third-party payors will be subject to applicable anti-kickback, fraud and abuse and other healthcare laws and regulations, which could expose us to significant penalties, including administrative, civil and criminal penalties, contractual damages, reputational harm and diminished profits and future earnings.
Risks Related to Government Regulation Our relationships with customers and third-party payors are subject to applicable anti-kickback, fraud and abuse and other healthcare laws and regulations, which could expose us to significant penalties, including administrative, civil and criminal penalties, contractual damages, reputational harm and diminished profits and future earnings.
There may be delays in getting our product candidates, if approved, on hospital or insurance formularies or limitations on coverages that may be available in the early stages of commercialization for newly approved drugs.
There may be delays in getting our products or product candidates on hospital or insurance formularies or limitations on coverages that may be available in the early stages of commercialization for newly approved drugs.
Our NDA submission may receive a refusal to file response from the FDA, and even if filed by the FDA, we may receive a Complete Response Letter rather than approval for commercial marketing. In addition, we may be required by the FDA to conduct additional clinical trials and/or nonclinical studies to support potential approval.
Our future NDA submissions may receive a refusal to file response from the FDA, and even if filed by the FDA, we may receive a Complete Response Letter rather than approval for commercial marketing. In addition, we may be required by the FDA to conduct additional clinical trials and/or nonclinical studies to support potential approval.
If we are unable to complete development of mavorixafor or any other product candidates that we may develop, we will not be able to commercialize and earn revenue from them. We may develop mavorixafor, and potentially future product candidates, in combination with other therapies, which could expose us to additional risks.
If we are unable to complete development for additional indications for mavorixafor or any other product candidates that we may develop, we will not be able to commercialize and earn revenue from them. We may develop mavorixafor, and potentially future product candidates, in combination with other therapies, which could expose us to additional risks.
For example, the federal government has levied large civil and criminal fines against companies for alleged improper promotion and in some instances has also required companies to enter into corporate integrity agreements under which specified promotional conduct is changed or curtailed.
For example, the federal government has levied large civil and criminal fines against companies for alleged improper promotion and in some instances has also required companies to enter into corporate integrity agreements or imposed permanent injunctions under which specified promotional conduct is changed or curtailed.
Obtaining and maintaining adequate reimbursement for mavorixafor may be particularly difficult because of the higher prices typically associated with drugs directed at smaller populations of patients.
Obtaining and maintaining adequate reimbursement for XOLREMDI may be particularly difficult because of the higher prices typically associated with drugs directed at smaller populations of patients.
In some cases, the price that we intend to charge for any product candidates, if approved, is also subject to approval. Obtaining approval for any future product candidates in the European Union from the European Commission following the opinion of the EMA would be a lengthy and expensive process.
In some cases, the price that we intend to charge for any product candidates, is also subject to approval. Obtaining approval for any future product candidates in the European Union from the European Commission following the opinion of the 43 EMA would be a lengthy and expensive process.
We believe that any of these events could prevent us from achieving or maintaining market acceptance of the affected product candidates and could substantially increase the costs of commercializing our product candidates, if approved, and significantly impact our ability to successfully commercialize our product candidates and generate revenues.
We believe that any of these events could prevent us from achieving or maintaining market acceptance of the affected product or product candidates and could substantially increase the costs of commercializing our products or product candidates, and significantly impact our ability to successfully commercialize our products or product candidates and generate revenues.
On November 13, 2023, we received a letter from the Listing Qualifications Staff of The Nasdaq Stock Market LLC ("Nasdaq") indicating that, based upon the closing bid price of our common stock for the last 30 consecutive business days, we no longer meet Nasdaq Listing Rule 5550(a)(2), which requires listed companies to maintain a minimum bid price of at least $1.00 per share.
On August 13, 2024, we received a letter from the Listing Qualifications Staff of The Nasdaq Stock Market LLC (“Nasdaq”) indicating that, based upon the closing bid price of our common stock for the last 30 consecutive business days, we no longer meet Nasdaq Listing Rule 5550(a)(2), which requires listed companies to maintain a minimum bid price of at least $1.00 per share.
We are not permitted to market mavorixafor or any other product candidate in the United States until we receive approval of an New Drug Application (“NDA”) from the FDA, or in any foreign countries until we receive the requisite approval from such countries or jurisdictions, such as approval of the marketing authorization application in the European Union from the European Commission.
We are not permitted to market mavorixafor or any other product candidate in the United States until we receive approval of an NDA from the FDA, or in any foreign countries until we receive the requisite approval from such countries or jurisdictions, such as approval of the marketing authorization application in the European Union from the European Commission.
In addition, the FDA and other regulatory authorities require that our product candidates and any products that we may eventually commercialize be manufactured according to cGMP and similar foreign standards.
In addition, the FDA and other regulatory authorities require that our product or product candidates that we may eventually commercialize be manufactured according to cGMP and similar foreign standards.
Our current and future arrangements with third-party payors and customers may expose us to broadly applicable fraud and abuse and other healthcare laws and regulations that may constrain the business or financial arrangements and relationships 48 through which we research, as well as market, sell and distribute any products for which we obtain marketing approval.
Our current and future arrangements with third-party payors and customers may expose us to broadly applicable fraud and abuse and other healthcare laws and regulations that may constrain the business or financial arrangements and relationships through which we research, market, sell and distribute XOLREMDI or any products candidates for which we obtain marketing approval in the future.
Even if we obtain regulatory approval, our product candidates may be approved for fewer or more limited indications than we request, such approval may be contingent on the performance of costly post-marketing clinical trials, or we may not be allowed to include the labeling claims necessary or desirable for the successful commercialization of such product candidate.
If our current or future product candidates receive regulatory approval, these product candidates may be approved for fewer or more limited indications than we request, such approval may be contingent on the performance of costly post-marketing clinical trials, or we may not be allowed to include the labeling claims necessary or desirable for the successful commercialization of such product candidate.
Section 382 of the Internal Revenue Code of 1986, as amended, or Section 382, contains rules that limit the ability of a company that undergoes an ownership change to utilize its net operating losses, or NOLs, and tax credits existing as of the date of such ownership change.
Section 382 of the Internal Revenue Code of 1986, as amended (“Section 382”) contains rules that limit the ability of a company that undergoes an ownership change to utilize its net operating losses (“NOLs”) and tax credits existing as of the date of such ownership change.
If we experience problems with these third parties, the manufacturing of mavorixafor could be delayed, which could harm our results of operations. • We rely on third-party CROs to conduct our preclinical studies and clinical trials.
If we experience problems with these third parties, the manufacturing of mavorixafor could be delayed, which could harm our results of operations. • We rely on third-party contract research organizations (“CROs”) to conduct our preclinical studies and clinical trials.
Our inability to promptly obtain coverage and adequate reimbursement rates from both government-funded and private payors for any approved products that we develop could have a material adverse effect on our operating results, our ability to raise capital needed to develop product candidates and commercialize products and our overall financial condition.
Our inability to promptly obtain coverage and adequate reimbursement rates from both government-funded and private payors for XOLREMDI (mavorixafor) or for any future approved product candidates could have a material adverse effect on our operating results, our ability to raise capital needed to develop additional product candidates and commercialize products and our overall financial condition.
Food and Drug Administration (“FDA”) and comparable foreign regulatory authorities, including the potential for the FDA or comparable foreign regulatory authorities to require that we perform more studies for our product candidates than those that we currently expect; • our ability to obtain marketing approval for our product candidates; • the scope, number, initiation, progress, timing, costs, design, duration, any potential delays, and results of clinical trials and nonclinical studies for our current or future product candidates; • the clinical development plans that we establish for these product candidates; • the number and characteristics of product candidates and programs that we develop or may in-license; • the cost of filing, prosecuting, defending and enforcing our patent claims and other intellectual property rights covering our product candidates, including any such patent claims and intellectual property rights that we have licensed from Genzyme pursuant to the terms of our license agreement with Genzyme or from other third parties; • our ability to maintain, expand and defend the scope of our intellectual property portfolio, including the cost of defending intellectual property disputes, including patent infringement actions brought by third parties against us or our product candidates; • the cost and timing of completion of commercial-scale manufacturing activities with respect to our product candidates; • our ability to establish and maintain licensing, collaboration or similar arrangements on favorable terms and whether and to what extent we retain development or commercialization responsibilities under any new licensing, collaboration or similar arrangement; • the cost of establishing sales, marketing and distribution capabilities for any product candidates for which we may receive regulatory approval in regions where we choose to commercialize our products on our own; • the success of any other business, product or technology that we acquire or in which we invest; • the costs of acquiring, licensing or investing in businesses, product candidates and technologies; • our need and ability to hire additional management and scientific and medical personnel; • market acceptance of our product candidates, to the extent any are approved for commercial sale; • the effect of competing technological and market developments; • the costs to operate as a public company; and 33 • business interruptions resulting from pandemics and public health emergencies, geopolitical actions, including war and terrorism or natural disasters including earthquakes, typhoons, floods and fires.
Our future funding requirements, both near and long-term, will depend on many factors, including, but not limited to: • the outcome, timing and cost of regulatory reviews, approvals or other actions to meet regulatory requirements established by the FDA and comparable foreign regulatory authorities, including the potential for the FDA or comparable foreign regulatory authorities to require that we perform more studies for our product candidates than those that we currently expect; • our ability to obtain marketing approval for our product candidates, including for additional indications; • the success of our exclusive licensing and supply agreement which Norgine and any potential regulatory and commercial milestone payments that we may receive under that agreement; • the scope, number, initiation, progress, timing, costs, design, duration, any potential delays, and results of clinical trials and nonclinical studies for our current or future product candidates; • the number and characteristics of product candidates and programs that we develop or may in-license; • the cost of filing, prosecuting, defending and enforcing our patent claims and other intellectual property rights covering our product candidates, including any such patent claims and intellectual property rights that we have licensed from Genzyme pursuant to the terms of our license agreement with Genzyme or from other third parties; • our ability to maintain, expand and defend the scope of our intellectual property portfolio, including the cost of defending intellectual property disputes, including patent infringement actions brought by third parties against us or our product candidates; • the cost and timing of completion of commercial-scale manufacturing activities with respect to our product candidates; • our ability to establish and maintain licensing, collaboration or similar arrangements on favorable terms and whether and to what extent we retain development or commercialization responsibilities under any new licensing, collaboration or similar arrangement; • the cost of establishing sales, marketing and distribution capabilities for any product candidates for which we may receive regulatory approval in regions where we choose to commercialize our products on our own; • the success of any other business, product or technology that we acquire or in which we invest; • the costs of acquiring, licensing or investing in businesses, product candidates and technologies; • our need and ability to hire additional management and scientific and medical personnel; • market acceptance of our product candidates, to the extent any are approved for commercial sale; • the effect of competing technological and market developments; • the costs to operate as a public company; and • business interruptions resulting from pandemics and public health emergencies, geopolitical actions, including war and terrorism or natural disasters including earthquakes, typhoons, floods and fires.

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Item 1C. Cybersecurity

Cybersecurity — threats and controls disclosure

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Biggest changeAlong with members of our finance, legal, and operations teams, the Director of IT sits on a newly-formed cyber subcommittee (“subcommittee”). The subcommittee reports to the Chief Operating Officer (“COO”) and Chief Financial Officer (“CFO”), and outputs from the Committee are provided by the COO and CFO to the Company’s executive team and the board.
Biggest changeWe have a cyber subcommittee (the “Subcommittee”), which includes members of our finance, legal, and IT departments, that meets periodically to discuss the Company’s ongoing cybersecurity efforts. The Subcommittee reports to the Chief Operating Officer (“COO”) and Chief Financial Officer (“CFO”), who report outputs from the Subcommittee regarding potential cybersecurity risks to the Company’s executive team and the board.
We have also developed an incident response policy and procedure designed to facilitate the timely reporting and assessment of cybersecurity incidents. Our cybersecurity risk management program, which is part of our enterprise risk management program, aims to identify risks related to the Company, including risks from cybersecurity threats.
We have also developed an incident response policy and procedure designed to facilitate the timely reporting and assessment of cybersecurity incidents. 63 Our cybersecurity risk management program, which is part of our enterprise risk management program, aims to identify risks related to the Company, including risks from cybersecurity threats.
The board is responsible for informed oversight of our risk management process. The board administers this oversight function through various board standing committees that address risks inherent in their respective areas of oversight. The board has delegated oversight for cybersecurity risk management to the Audit Committee.
The Director of Infrastructure, Operations & Cybersecurity is responsible for the day-to-day monitoring and remediation of cybersecurity risks. The board is responsible for informed oversight of our risk management process. The board administers this oversight function through various board standing committees that address risks inherent in their respective areas of oversight.
We have identified cybersecurity as a critical business risk as part of our overall risk management strategy, which our board of directors oversees. 66 We have implemented a cybersecurity program in accordance with our risk profile and business that includes, among other things, written policies, monitoring and filtering procedures, and employee training.
We have implemented a cybersecurity program in accordance with our risk profile and business that includes, among other things, written policies, monitoring and filtering procedures, and employee training.
The Audit Committee reviews the Company’s policies and procedures with respect to cybersecurity risk management. Although risks from cybersecurity threats have to date not materially affected us, our business strategy, results of operations or financial condition, we have, from time to time, experienced threats to and breaches of our and our third-party vendors’ data and systems.
Although risks from cybersecurity threats have to date not materially affected us, our business strategy, results of operations or financial condition, we have, from time to time, experienced threats to and breaches of our and our third-party vendors’ data and systems. For more information, see Item 1A. Risk Factors.
ITEM 1C. CYBERSECURITY Cybersecurity Risk Management and Strategy Our management recognizes the impact that cybersecurity threats could have on our business operations, our compliance with regulations, and our reputation.
ITEM 1C. CYBERSECURITY Cybersecurity Risk Management and Strategy Our management recognizes the impact that cybersecurity threats could have on our business operations, our compliance with regulations, and our reputation. We have identified cybersecurity as a critical business risk as part of our overall risk management strategy, which our board of directors oversees.
Our vendor evaluation procedures include, as appropriate, the review of vendors’ SOC 2 Type 2 reports if available, and a vendor security questionnaire. We are in the process of expanding the use of the security questionnaire to additional vendors.
Our vendor evaluation procedures include, as appropriate, the review of vendors’ SOC 2 Type 2 reports and a vendor security questionnaire. Governance Related to Cybersecurity Risks Our Director of Infrastructure, Operations and Cybersecurity, who has over ten years of experience managing organizational operations, security and infrastructure, manages the Company’s cybersecurity program.
Removed
Governance Related to Cybersecurity Risks Our director of information technology (“Director of IT”) is responsible for the strategic leadership and direction of the Company’s information technology organization. The Director of IT has helped organizations define and implement information technology strategies for over twenty years. Prior to joining the Company, he served in senior information technology roles for several biotechnology companies.
Added
The board has delegated oversight for cybersecurity risk management to the Audit Committee. The Audit Committee reviews the Company’s policies and procedures with respect to cybersecurity risk management.
Removed
For more information, see Item 1A. Risk Factors. The pharmaceutical industry is highly competitive and is subject to rapid and significant technological change, which could render our technologies and products obsolete or uncompetitive.

Item 2. Properties

Properties — owned and leased real estate

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Biggest changeThe base monthly payment on the lease is approximately $91 thousand as of December 31, 2023, subject to specified annual increases of approximately 3% during the term of the lease and not including operating expenses, certain utilities, taxes and insurance for which we are responsible.
Biggest changeThe base monthly payment on the lease is approximat ely $91 thousand as of December 31, 2024, s ubject to specified annual increases of approximately 3% during the term of the lease and not including operating expenses, certain utilities, taxes and insurance for which we are responsible.
LEGAL PROCEEDINGS From time to time, we may be involved in lawsuits, claims, investigations and proceedings, consisting of intellectual property, commercial, employment and other matters which arise in the ordinary course of business. While the outcome of any such proceedings cannot be predicted with certainty, as of December 31, 2023, we were not party to any legal proceedings. 67
LEGAL PROCEEDINGS From time to time, we may be involved in lawsuits, claims, investigations and proceedings, consisting of intellectual property, commercial, employment and other matters which arise in the ordinary course of business. While the outcome of any such proceedings cannot be predicted with certainty, as of December 31, 2024, we were not party to any legal proceedings.

Item 3. Legal Proceedings

Legal Proceedings — active lawsuits and investigations

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Biggest changeItem 3. LEGAL PROCEEDINGS 67 Item 4 . MINE SAFETY DISCLOSURES 68 PART II Item 5. MARKET FOR REGISTRANT'S COMMON EQUITY, RELATED STOCKHOLDER MATTERS AND ISSUER PURCHASES OF EQUITY SECURITIES 69 Item 6. [RESERVED] 69 Item 7. MANAGEMENT'S DISCUSSION AND ANALYSIS OF FINANCIAL CONDITION AND RESULTS OF OPERATIONS 70
Biggest changeItem 3. LEGAL PROCEEDINGS 64 Item 4 . MINE SAFETY DISCLOSURES 64 PART II Item 5. MARKET FOR REGISTRANT ’ S COMMON EQUITY, RELATED STOCKHOLDER MATTERS AND ISSUER PURCHASES OF EQUITY SECURITIES 65 Item 6. [RESERVED] 65 Item 7. MANAGEMENT ’ S DISCUSSION AND ANALYSIS OF FINANCIAL CONDITION AND RESULTS OF OPERATIONS 66

Item 5. Market for Registrant's Common Equity

Market for Common Equity — stock, dividends, buybacks

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Biggest changeHolders of Our Common Stock As of March 1, 2024, there were 60 holders of record of our common stock, one of which is Cede & Co., a nominee for Depository Trust Company (“DTC”).
Biggest changeHolders of Our Common Stock As of March 13, 2025, there were 48 holders of record of our common stock, one of which is Cede & Co., a nominee for Depository Trust Company (“DTC”).

Item 7. Management's Discussion & Analysis

Management's Discussion & Analysis (MD&A) — revenue / margin commentary

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Biggest changeFor further discussion of the potential impacts of macroeconomic events on our business, financial condition, and operating results, see the section titled “Risk Factors.” Results of Operations Comparison of the Years Ended December 31, 2023 and 2022 The following table summarizes the results of our operations for the periods indicated: Year Ended December 31, 2023 2022 Change (in thousands) Operating expenses: Research and development $ 72,017 $ 61,058 $ 10,959 Selling, general and administrative 35,505 27,020 8,485 Gain on sale of non-financial asset — (509) 509 Total operating expenses 107,522 87,569 19,953 Loss from operations (107,522) (87,569) (19,953) Total other income (expense), net 6,433 (6,270) 12,703 Loss before provision for income taxes (101,089) (93,839) (7,250) Provision for income taxes 78 28 50 Net loss $ (101,167) $ (93,867) $ (7,300) Research and Development Expenses Research and development expenses consist primarily of costs incurred in connection with the discovery and development of our product candidates, including employee salaries and related expenses, expenses incurred in connection with the preclinical and clinical development of our product candidates, including under agreements with third parties, such as consultants and contract research organizations (“CROs”); the cost of manufacturing drug products for use in our preclinical studies and clinical trials, including under agreements with third parties, such as consultants and contract manufacturing organizations (“CMOs”); facilities, depreciation and other expenses, which include direct or allocated expenses for rent and maintenance of facilities and insurance; costs related to compliance with regulatory requirements; and payments made under third-party licensing agreements.
Biggest changeResearch and Development Expenses Research and development expenses consist primarily of costs incurred in connection with the development of our product candidates, including employee salaries and related expenses for personnel in our clinical operations, biostatistics, medical affairs, manufacturing and technical, quality and regulatory affairs departments; external expenses incurred in connection with the clinical development of our product candidates, including under agreements with third parties, such as consultants and contract research organizations (“CROs”); the cost of manufacturing drug products for use in our clinical trials, including under agreements with third parties, such as consultants and contract manufacturing organizations (“CMOs”); facilities, depreciation and other expenses, which include direct or allocated expenses for rent and maintenance of facilities and insurance; and costs related to compliance with regulatory requirements.
We have entered into a common stock purchase agreement with Lincoln Park Capital, pursuant to which Lincoln Park Capital has committed to purchase, at our request from time to time over a 36-month period, shares of our common stock having an aggregate offering price of up to $50.0 million, of which $3.0 million have been sold to date, subject to certain limitations.
We entered into a common stock purchase agreement with Lincoln Park Capital, pursuant to which Lincoln Park Capital has committed to purchase, at our request from time to time over a 36-month period, shares of our common stock having an aggregate offering price of up to $50.0 million, of which $3.0 million have been sold to date, subject to certain limitations.
The financial terms of these agreements are subject to negotiation, vary from contract to contract and may result in uneven payment flows. There may be instances in which payments made to our vendors will exceed the level of 77 services provided and result in a prepayment of the expense.
The financial terms of these agreements are subject to negotiation, vary from contract to contract and may result in uneven payment flows. There may be instances in which payments made to our vendors will exceed the level of services provided and result in a prepayment of the expense.
To perform its quantitative test, we compare the fair value of our single reporting unit to the carrying value of its net assets, including goodwill. We use our market capitalization (common shares outstanding multiplied by the price per share of our common stock) to measure the fair 78 value of the reporting unit.
To perform its quantitative test, we compare the fair value of our single reporting unit to the carrying value of its net assets, including goodwill. We use our market capitalization (common shares outstanding multiplied by the price per share of our common stock) to measure the fair value of the reporting unit.
In March 2022, we sold shares of common stock and, in lieu of common stock, pre-funded warrants to purchase shares of common stock in a private placement for gross proceeds of $3.0 million, before offering expenses.
For example, In March 2022, we sold shares of common stock and, in lieu of common stock, pre-funded warrants to purchase shares of common stock in a private placement for gross proceeds of $3.0 million, before offering expenses.
For the discussion of the financial condition and results of operations for the year ended December 31, 2022 compared to the year ended December 31, 2021, refer to “Management’s Discussion and Analysis of Financial Condition and Results of Operations” to our Annual Report on Form 10-K filed with the SEC on March 21, 2023.
For the discussion of the financial condition and results of operations for the year ended December 31, 2023 compared to the year ended December 31, 2022, refer to “Management’s Discussion and Analysis of Financial Condition and Results of Operations” to our Annual Report on Form 10-K filed with the SEC on March 21, 2024.
To finance our operations, we will need to raise additional capital, which cannot be assured. Unless and until we reach profitability in the future, we will require additional capital to fund our operations, which could be raised through a combination of equity offerings, debt financings, other third-party funding, marketing and distribution arrangements and other collaborations and strategic alliances.
Unless and until we reach profitability in the future, we will require additional capital to fund our operations, which could be raised through a combination of equity offerings, debt financings, other third-party funding, marketing and distribution arrangements, or other collaborations and strategic alliances.
Noncash expenses primarily includes stock-based compensation expense of $8.7 million and non-cash lease expense of $1.6 million, partially offset by $7.1 million of non-cash gains on the change in fair value of our Class C Warrant liability.
Noncash expenses primarily include stock-based compensation expense of $8.2 million and non-cash lease expense of $1.6 million, partially offset by $1.9 million of non-cash gains on the change in fair value of our Class C Warrant liability.
Our short term and long term funding requirements will depend on and could increase significantly as a result of many factors, including: • the scope, number, initiation, progress, timing, costs, design, duration, any potential delays, and results of clinical trials and nonclinical studies for our current or future product candidates, particularly our Phase 2 clinical trial of mavorixafor for the treatment of patients with chronic neutropenic disorders; • the outcome, timing and cost of regulatory reviews, approvals or other actions to meet regulatory requirements established by the FDA and comparable foreign regulatory authorities, including the potential for the FDA or comparable foreign regulatory authorities to require that we perform more studies for our product candidates than those that we currently expect; • our ability to obtain marketing approval for our product candidates; • the cost of filing, prosecuting, defending and enforcing our patent claims and other intellectual property rights covering our product candidates, including any such patent claims and intellectual property rights that we have licensed from Genzyme pursuant to the terms of our license agreement with Genzyme; • our ability to maintain, expand and defend the scope of our intellectual property portfolio, including the cost of defending intellectual property disputes, including patent infringement actions brought by third parties against us or our product candidates; • the cost and timing of completion of commercial-scale manufacturing activities with respect to our product candidates; • our ability to establish and maintain licensing, collaboration or similar arrangements on favorable terms and whether and to what extent we retain development or commercialization responsibilities under any new licensing, collaboration or similar arrangement; • the cost of establishing sales, marketing and distribution capabilities for any product candidates for which we may receive regulatory approval in regions where we choose to commercialize our products on our own; • the success of any other business, product or technology that we acquire or in which we invest; • the costs of acquiring, licensing or investing in businesses, product candidates and technologies; • our need and ability to hire additional management and scientific and medical personnel; • market acceptance of our product candidates, to the extent any are approved for commercial sale; • the effect of competing technological and market developments; and • the costs to operate as a public company 76 Until such time, if ever, as we can generate substantial product revenue, we expect to finance our cash needs through a combination of equity offerings, debt financings, collaborations, strategic alliances, and marketing, distribution or licensing arrangements with third parties.
Our short-term and long-term funding requirements will depend on and could increase significantly as a result of many factors, including: • the scope, number, initiation, progress, timing, costs, design, duration, any potential delays, and results of clinical trials and nonclinical studies for our current or future product candidates, particularly our Phase 3 clinical trial of mavorixafor for the treatment of individuals with chronic neutropenic disorders; • the outcome, timing and cost of regulatory reviews, approvals or other actions to meet regulatory requirements established by the FDA and comparable foreign regulatory authorities, including the potential for the FDA or comparable foreign regulatory authorities to require that we perform more studies for our product candidates than those that we currently expect; • our ability to obtain marketing approval for our product candidates; • the cost of filing, prosecuting, defending and enforcing our patent claims and other intellectual property rights covering our product and product candidates, including any such patent claims and intellectual property rights that we have licensed from Genzyme pursuant to the terms of our license agreement with Genzyme; • our ability to maintain, expand and defend the scope of our intellectual property portfolio, including the cost of defending intellectual property disputes, including patent infringement actions brought by third parties against us or our product or product candidates; • our ability to establish and maintain licensing, collaboration or similar arrangements on favorable terms and whether and to what extent we retain development or commercialization responsibilities under any new licensing, collaboration or similar arrangement; • the success of any other business, product or technology that we acquire or in which we invest; • the costs of acquiring, licensing or investing in businesses, product candidates and technologies; • the effect of competing technological and market developments; and • the costs to operate as a public company Until such time, if ever, as we can generate substantial product revenue, we expect to finance our cash needs through a combination of equity offerings, debt financings, collaborations, strategic alliances, and marketing, distribution or licensing arrangements with third parties.
ATM Sales Agreement — We have entered into a Controlled Equity Offering SM Sales Agreement (“ATM Sales Agreement”), with B.
ATM Sales Agreement — On August 7, 2020, we have entered into a Controlled Equity Offering SM Sales Agreement (“ATM Sales Agreement”), with B.
Because of the numerous risks and uncertainties associated with research, development and commercialization of pharmaceutical product candidates, we are unable to estimate the exact amount of our funding requirements.
However, because of the numerous risks and uncertainties associated with the future sale of our approved drug product and the research, development, and commercialization of future product candidates, we are unable to estimate the exact amount of our funding requirements.
The shares of 73 common stock that we may sell under the LPC Agreement are capped at an aggregate of 5.6 million shares, which amount may be adjusted under certain conditions as defined in the LPC Agreement. In January 2022, we raised $3.0 million from the sale of shares of our common stock through the LPC Agreement.
The shares of common stock that we may sell under the LPC Agreement are capped at an aggregate of 5.6 million shares, which amount may be adjusted under certain conditions as defined in the LPC Agreement.
W e do not expect to record a significant income tax benefit or expense for several years as we have significant net operating loss carryforwards that are fully reserved until such time as we begin to generate meaningful taxable income in our U.S. jurisdiction.
W e do not expect to record a significant income tax benefit or expense for several years until such time as we begin to generate meaningful and sustained taxable income in our U.S. jurisdiction.
Borrowings under the Hercules Loan Agreement accrues interest at a variable rate equal to the greater of (i) 10.15% or (ii) 3.15% plus the Wall Street Journal prime rate and are repayable in monthly interest-only payments through March 1, 2025, and in equal monthly payments of principal and accrued interest from April 1, 2025 until the maturity date of the loans, which is currently October 1, 2026, subject to extension upon our achievement of certain operational milestones.
Borrowings under the Hercules Loan Agreement accrues interest at a variable rate equal to the greater of (i) 10.15% or (ii) 3.15% plus the Wall Street Journal prime rate and are repayable in monthly interest-only payments through March 1, 2027, and in equal monthly payments of principal and accrued interest until July 1, 2027, which is the maturity date of the loans.
The fair value of stock option grants is estimated on the date of grant using the Black-Scholes option-pricing model, which uses as inputs the fair value of our common stock and assumptions we make for the volatility of our common stock, the expected term of the stock options, the risk-free interest rate for a period that approximates the expected term of our stock options and an expected dividend yield.
We update our estimates related to the probability and timing of achievement of the operational milestones each period until the award either vests or is forfeited . 74 The fair value of stock option grants is estimated on the date of grant using the Black-Scholes option-pricing model, which uses as inputs the fair value of our common stock and assumptions we make for the volatility of our common stock, the expected term of the stock options, the risk-free interest rate for a period that approximates the expected term of our stock options and an expected dividend yield.
If we are unable to obtain funding, we could be forced to delay, reduce or eliminate some or all of our research and development programs, product portfolio expansion or commercialization efforts, which would adversely affect our business prospects, or we may be unable to continue operations . 74 Cash Flows The following table summarizes our cash flow activities for each of the periods presented: Year Ended December 31, 2023 2022 (in thousands) Net loss $ (101,167) $ (93,867) Adjustments to reconcile net loss to net cash used in operating activities 4,311 11,029 Changes in operating assets and liabilities 344 5,736 Net cash used in operating activities (96,512) (77,102) Net cash used in investing activities (14,883) (103) Net cash provided by financing activities 88,516 117,230 Impact of foreign exchange on cash and restricted cash 99 (105) Net increase in cash, cash equivalents and restricted cash (22,780) 39,920 Cash, cash equivalents and restricted cash, beginning of period 123,028 83,108 Cash, cash equivalents and restricted cash, end of period $ 100,248 $ 123,028 Operating Activities: During the year ended December 31, 2023, net cash used in operating activities was $96.5 million, primarily resulting from our net losses of $101.2 million, adjusted for noncash expenses of $4.3 million and changes in our operating assets and liabilities of $0.3 million.
If we are unable to obtain funding, we could be forced to delay, reduce, or eliminate some or all of our research and development programs, product portfolio expansion or commercialization efforts, which would adversely affect our business prospects, or we may be unable to continue operations. 71 Cash Flows The following table summarizes our cash flow activities for each of the periods presented: Year Ended December 31, 2024 2023 (in thousands) Net loss $ (37,450) $ (101,167) Adjustments to reconcile net loss to net cash used in operating activities (96,126) 4,311 Changes in operating assets and liabilities 2,675 344 Net cash used in operating activities (130,901) (96,512) Net cash provided by (used in) investing activities 66,990 (14,883) Net cash provided by financing activities 20,294 88,516 Impact of foreign exchange on cash and restricted cash (156) 99 Net decrease in cash, cash equivalents and restricted cash (43,773) (22,780) Cash, cash equivalents and restricted cash, beginning of period 100,248 123,028 Cash, cash equivalents and restricted cash, end of period $ 56,475 $ 100,248 Operating Activities: During the year ended December 31, 2024, net cash used in operating activities was $130.9 million, primarily resulting from our operating losses and other (expense) income, net, of $142.5 million adjusted for noncash expenses of $8.9 million and changes in our operating assets and liabilities of $2.7 million.
If we are unable to raise additional funds through equity or debt financings or other arrangements when needed, we may be required to delay, reduce or eliminate our product development efforts or future commercialization efforts, or grant rights to develop and market product candidates that we would otherwise prefer to develop and market ourselves.
If we are unable to raise additional funds through equity or debt financings or other arrangements when needed, we may be required to delay, reduce or eliminate our product development efforts or future commercialization efforts, or grant rights to develop and market product candidates that we would otherwise prefer to develop and market ourselves. 73 Critical Accounting Policies and Estimates Our consolidated financial statements are prepared in accordance with generally accepted accounting principles in the United States.
Public and Private Equity Offerings — Over the past several years we have funded our operations primarily from sales of common stock, warrants and prefunded warrants through both public offerings and private placements.
In January 2022, we raised $3.0 million from the sale of shares of our common stock through the LPC Agreement. 70 Public and Private Equity Offerings — Over the past several years we have funded our operations primarily from sales of common stock, warrants and prefunded warrants through both public offerings and private placements.
In order to fund operations and satisfy the minimum cash covenant in the Hercules Loan Agreement, we will be required to raise additional capital, which may be through a combination of equity offerings, debt financings, other third-party funding, marketing and distribution arrangements, the sale of a PRV that may be granted to us if we receive FDA approval of our NDA, profits generated from the sale of our drug candidate upon the receipt of FDA approval of our NDA and other collaborations and strategic alliances.
In order to fund operations and satisfy the Minimum Cash Covenant in the Hercules Loan Agreement, we will be required to raise additional capital, which may be through a combination of equity offerings, debt financings, other third-party funding, marketing and distribution arrangements, or collaborations and strategic alliances.
Material Capital Requirements Debt Obligations See Note 7 of the consolidated financial statements and in “Sources of Liquidity” above for a description of our debt obligation. Lease Obligations We have long-term lease obligations for office and laboratory space. Non-cancellable lease obligations are $1.4 million in 2024, $1.4 million in 2025, $1.3 million in 2026, and $0.3 million thereafter.
Material Capital Requirements Debt Obligations See Note 10 of the consolidated financial statements and in “Sources of Liquidity” above for a description of our debt obligation. Lease Obligations We have long-term lease obligations for office and laboratory space.
We expect that our research and development expenses, particularly for our mavorixafor programs, will increase over the next several years as we continue to conduct our clinical trials of mavorixafor in chronic neutropenic disorders. Research and development expenses related to our X4P-002 and X4P-003 programs was not significant in 2023 or 2022 relative to our overall research and development expenses.
We expect that our research and development expenses, particularly for our mavorixafor programs, will be relatively consistent over the next several years as we continue to conduct our clinical trials of mavorixafor in chronic neutropenic disorders.
Recently Issued Accounting Pronouncements There are no recently issued accounting pronouncements that may potentially cause a material impact our financial position and results of operations. ITEM 7A. QUANTITATIVE AND QUALITATIVE DISCLOSURES ABOUT MARKET RISK As a smaller reporting company, we are not required to provide disclosure for this Item.
Recently Issued Accounting Pronouncements See Note 2 to the consolidated financial statements. ITEM 7A. QUANTITATIVE AND QUALITATIVE DISCLOSURES ABOUT MARKET RISK As a smaller reporting company, we are not required to provide disclosure for this Item.
Financing Activities: During the year ended December 31, 2023, net cash provided by financing activities was $88.5 million, consisting primarily of net proceeds from a private placement of our common stock, warrants, and pre-funded warrants, a $22.5 million term loan tranche drawn on the closing of the Amendment of our Hercules Loan Agreement and the exercise of outstanding warrants during the year.
During the year ended December 31, 2023, net cash provided by financing activities was $88.5 million, primarily due to $60.0 million of proceeds from the sale of our common stock and pre-funded warrants, borrowing net of repayments and issuance costs of $19.8 million on our Hercules Loan Agreement, and $8.7 million of proceeds from warrant exercises.
The change in operating assets and liabilities was primarily due to an increase in accounts payable and accrued expenses due to the timing of payments related to our CROs. Cash used in operating activities was higher for the year ended December 31, 2023 as compared to the prior year primarily due to higher net losses in the current year.
Cash used in operating activities was higher for the year ended December 31, 2024 as compared to the prior year primarily due to higher net losses in the current year.
As noted above, we have a covenant under our Hercules Loan Agreement that currently requires that we maintain a minimum level of cash of $20.0 million through January 31, 2025, subject to subsequent reductions thereafter.
We have a covenant (the “Minimum Cash Covenant”) under our Hercules Loan Agreement that effective January 31, 2025 requires that we maintain a minimum level of cash of $15 million, representing 20% of outstanding borrowings under the Hercules Loan Agreement.
In anticipation of a potential second quarter of 2024 U.S. launch of mavorixafor in WHIM syndrome, we have continued to build our go-to-market organization, with key hires across commercial and medical functions, increased interactions with key stakeholders and rare disease patient advocacy organizations, and launched a disease-awareness campaign aiming to further the understanding of WHIM syndrome and educate patients and physicians on the importance and benefits of early diagnosis.
XOLREMDI Commercial Launch We are currently engaged in our U.S. launch of XOLREMDI in WHIM syndrome, continuing our engagements with physicians and rare disease patient advocacy organizations and our disease-awareness campaign to further the understanding of WHIM syndrome and educate patients and physicians on the importance and benefits of early diagnosis.
Due to its ability to increase the mobilization of mature, functional white blood cells into the bloodstream, we believe that mavorixafor has the potential to provide therapeutic benefit across a variety of chronic neutropenic disorders, including WHIM (Warts, Hypogammaglobulinemia, Infections, and Myelokathexis) syndrome, a rare, primary immunodeficiency for which there are no approved therapies.
Due to its ability to increase the mobilization of white blood cells from the bone marrow into the bloodstream, we believe that mavorixafor has the potential to provide therapeutic benefit across a variety of immune system disorders in addition to WHIM syndrome.
Overview We are a late clinical-stage biopharmaceutical company discovering and developing novel therapeutics for the treatment of rare diseases and those with limited treatment options, with a focus on conditions resulting from dysfunction of the immune system. Our lead clinical candidate is mavorixafor, a small-molecule selective antagonist of chemokine receptor CXCR4 that is being developed as an oral, once-daily therapy.
Overview We are a biopharmaceutical company discovering, developing, and commercializing novel therapeutics for the treatment of rare diseases and those with limited treatment options, with a focus on conditions resulting from dysfunction of the immune system. On April 29, 2024, we announced that the U.S.
Investing Activities: During the year ended December 31, 2023, net cash used in investing activities was $14.9 million, primarily due to our net investment in short-term marketable securities. Cash used in investing activities was not significant for the year ended December 31, 2022.
Cash used in investing activities for the year ended December 31, 2023 was primarily related to net investments in short-term marketable securities. Financing Activities: During the year ended December 31, 2024, net cash provided by financing activities was $20.3 million, consisting primarily of proceeds borrowed on our Hercules Loan Agreement.
Selling, General and Administrative Expenses Selling, general and administrative expenses consist primarily of salaries and related costs, including stock-based compensation for personnel in sales and marketing, executive, finance and administrative functions. Selling, general and administrative expenses also include direct and allocated facility-related costs, as well as professional fees for legal, patent, consulting, investor and public relations, accounting, and audit services.
Selling, general and administrative expenses also include direct and allocated facility-related costs, as well as professional fees for legal, patent, consulting, investor and public relations, accounting, and audit services. Selling, general and administrative expenses increased by $26.0 million to $61.5 million for the year ended December 31, 2024 as compared to $35.5 million in the prior year.
Research and development expenses also increased in 2023 due to an increase in unallocated expenses, primarily due to an increase in head count within our manufacturing, regulatory and clinical operations functions, resulting in higher compensation expenses, including stock-based compensation.
Unallocated expense increased primarily due to an increase in personnel within our research and development functions, primarily in our clinical operations, biostatistics, medical affairs, manufacturing and technical, and quality organizations.
On August 2, 2023, we and Hercules entered into an amendment (the “Amendment”) to the Second A&R Hercules Loan Agreement, (as amended by the Amendment, the “Hercules Loan Agreement”), which provides for aggregate maximum borrowings of up to $115.0 million, including the $32.5 million outstanding prior to the Amendment, a $22.5 million term loan tranche drawn on the closing of the Amendment, and $60.0 million in potential additional borrowings.
Hercules Loan Agreement — We entered into a Loan and Security Agreement, as most recently amended in August 2023 with Hercules Capital, Inc, (the “Hercules Loan Agreement”). The Hercules Loan Agreement provides for an aggregate term loan facility of up to $107.5 million, less $75.0 million borrowed to date.
We expense research and development costs as incurred. 71 Year Ended December 31, 2023 2022 Change (in thousands) Direct research and development expenses by product candidate: Mavorixafor (X4P-001) $ 41,163 $ 30,041 $ 11,122 X4P-002 (34) 2,338 (2,372) X4P-003 75 206 (131) Unallocated expense 30,813 28,473 2,340 Total research and development expenses $ 72,017 $ 61,058 $ 10,959 Research and development expenses were $72.0 million for the year ended December 31, 2023, as compared to $61.1 million for the year ended December 31, 2022, reflecting an increase of $11.0 million.
We capitalized as intangible assets certain milestone payments due under our key in-license agreement. 68 Year Ended December 31, 2024 2023 Change (in thousands) Direct research and development expenses by product candidate: Mavorixafor (X4P-001) $ 41,483 $ 41,163 $ 320 X4P-002 159 (34) 193 X4P-003 150 75 75 Unallocated expense 39,851 30,813 9,038 Total research and development expenses $ 81,643 $ 72,017 $ 9,626 Research and development expenses increased by $9.6 million for the year ended December 31, 2024, as compared to the prior year primarily due to an increase in unallocated expense .
Other Income (Expense), Net Year Ended December 31, 2023 2022 Change (in thousands) Interest income $ 4,582 $ 219 $ 4,363 Interest expense (5,777) (3,993) (1,784) Change in fair value of warrant and derivative liabilities 7,074 1,701 5,373 Research and development incentive program 553 534 19 Foreign currency losses and issuance costs related to warrants 1 (4,731) 4,732 Total other income (expense), net $ 6,433 $ (6,270) $ 12,703 The increase in other income (expense), net, of $12.7 million for the year ended December 31, 2023 as compared to 2022 was primarily due (i) an increase in interest income earned on our marketable securities and cash equivalents due to higher invested balances and higher interest rates (ii) income resulting from the decrease in the fair value of outstanding Class C warrants, which are accounted for as a liability, due primarily to a decrease in the value of our common stock and, (iii) transaction fees incurred in 2022 that did not recur in 2023 associated with the issuance of warrants that are accounted for as liabilities, partially offset by an increase in interest expense associated with the Hercules Loan agreement due to higher borrowings and a higher effective interest rate.
As a result of the strategic restructuring of our workforce and capital spending to focus efforts on advancing mavorixafor to treat those with chronic neutropenia, while also optimizing its U.S. promotion of XOLREMDI, we expect that our operating expenses will decrease by approximately $30.0 million to $35.0 million in 2025. 69 Other (Expense) Income, Net Year Ended December 31, 2024 2023 Change (in thousands) Interest income $ 5,769 $ 4,582 $ 1,187 Interest expense (8,768) (5,777) (2,991) Change in fair value of warrant and derivative liabilities 1,928 7,074 (5,146) Research and development incentive program 659 553 106 Foreign currency (losses) gains (327) 1 (328) Total other (expense) income, net $ (739) $ 6,433 $ (7,172) The increase in other (expense) income, net, of $7.2 million for the year ended December 31, 2024 as compared to 2023 was primarily due (i) lower income resulting from the decrease in the fair value of outstanding Class C warrants, which are accounted for as a liability and are remeasured to fair value each period, as compared to the prior year and, (ii) an increase in interest expense associated with the Hercules Loan agreement due to more borrowings outstanding during the current period.
See Note 4 for more information on our goodwill impairment test as of December 31, 2023. Smaller Reporting Company Status We are a smaller reporting company as defined in the Exchange Act.
See Note 5 for more information on our goodwill impairment test as of December 31, 2024. Intangible Assets, Net.
We are now conducting a Phase 2 clinical trial, evaluating the durability, safety, and tolerability of chronic dosing of once-daily oral mavorixafor with or without concurrent treatment with injectable granulocyte colony-stimulating factor (“G-CSF”) in the same patient population. Preliminary results from the trial showed that the first three participants experienced clinically meaningful increases in ANC.
Phase 2 Clinical Study in Chronic Neutropenia Following positive results from a Phase 1b clinical study of a single dose of mavorixafor in people with idiopathic, cyclic, and congenital chronic neutropenia (“CN”), we recently completed and announced positive results from a Phase 2 clinical study evaluating the durability of effect, safety, and tolerability of chronic dosing of once-daily oral mavorixafor with or without concurrent treatment with injectable granulocyte colony-stimulating factor (“G-CSF”) in the same patient population. 66 The results from the completed six-month study showed that once-daily oral mavorixafor was generally well tolerated and durably increased participants’ absolute neutrophil counts (“ANC”) both as a monotherapy and in combination with G-CSF, the only therapy approved in the U.S. for severe chronic neutropenia.
Funding Requirements We believe that our current cash, cash equivalents and short-term marketable securities will allow us to fund operations into the first quarter of 2025.
Non-cancellable lease obligations are $1.4 million in 2025, $1.3 million in 2026, and $0.3 million thereafter. 72 Funding Requirements Based on our cash, cash equivalents and marketable securities on hand as of December 31, 2024 and our current operating plan, we believe that our cash, cash equivalents and marketable securities will not allow us to fund operations for at least the next 12 months.
During the year ended December 31, 2022, net cash provided by financing activities was $117.2 million, consisting primarily of proceeds from the sale of our common stock and pre-funded warrants in two a private placements and a public offering.
Investing Activities: During the year ended December 31, 2024, net cash provided by investing activities was $67.0 million, primarily due $105.0 million of cash from the sale of a PRV, partially offset by net investments in short-term marketable securities.
We believe that successfully developing mavorixafor and providing a new therapeutic option to individuals diagnosed with certain chronic neutropenic disorders has the potential to revolutionize the treatment landscape, which is principally served by injectable therapies (including G-CSF) that are frequently associated with treatment-limiting adverse events. To date, we have not generated revenue from product sales.
We believe that successfully developing and commercializing mavorixafor to provide a new therapeutic option to individuals diagnosed with certain immunodeficiencies has the potential to revolutionize the current treatment landscape, which is principally served by injectable and infused therapies. 2025 Restructuring In February 2025, we implemented a strategic restructuring of our business operations, workforce and capital spending to focus efforts on advancing mavorixafor to treat those with chronic neutropenia, while also optimizing its U.S. promotion of XOLREMDI (the “2025 Restructuring”).
Income Taxes For the years ended December 31, 2023 and 2022, we recorded income tax provisions related to our Austrian subsidiary and Securities Corp.
Our tax provision in the year ended December 31, 2023 was related to our U.S. security corporation, which holds our investment portfolio, and our Austrian subsidiary.
Removed
We are currently seeking approval from the U.S. Food and Drug Administration (“FDA”) for the use of oral, once-daily mavorixafor in the treatment of people aged 12 years and older with WHIM syndrome following the October 2023 acceptance of our New Drug Application (“NDA”) by the FDA.
Added
FDA approved our NDA for mavorixafor, which is being marketed in the U.S. under the trade name XOLREMDI, for use as an oral, once-daily therapy in patients aged 12 years of age and older with WHIM (warts, hypogammaglobulinemia, infections, and myelokathexis) syndrome, to increase the number of circulating mature neutrophils and lymphocytes.
Removed
The FDA has granted the NDA Priority Review, establishing a goal of six months review from the date of acceptance and assigning a Prescription Drug User Fee Act (“PDUFA”) target action date of April 30, 2024. At this time, the FDA has notified us that they are not currently planning to hold an advisory committee meeting to review the filing.
Added
WHIM syndrome (Warts, Hypogammaglobulinemia, Infections, and Myelokathexis) is a rare combined primary immunodeficiency and chronic neutropenic disorder. Concurrent with the U.S. approval of XOLREMDI and pursuant to its Rare Pediatric Disease designation, the FDA granted us a PRV that we sold to another drug sponsor shortly thereafter.
Removed
Due to mavorixafor’s Rare Pediatric Disease designation in the U.S. for WHIM syndrome, we are eligible to receive a Priority Review Voucher (“PRV”) that can be used to obtain Priority Review for a subsequent application or sold to another drug sponsor should mavorixafor be approved.
Added
We have entered into agreements with a third-party logistics organization and a specialty pharmacy to support the distribution of XOLREMDI in the U.S., to mitigate barriers to product access, and to provide a suite of patient support services to help patients through their treatment journey.
Removed
The NDA is supported by our successfully completed global, pivotal, Phase 3 clinical trial (4WHIM) that evaluated the safety and efficacy of mavorixafor in people with WHIM syndrome.
Added
We submitted a Marketing Authorisation Application (“MAA”) to the European Medicines Agency (“EMA”) in early 2025 seeking regulatory approval to commercialize mavorixafor for WHIM syndrome outside of the U.S. Such MAA was accepted for processing by the EMA in January 2025.
Removed
The 4WHIM trial met its primary endpoint and a key secondary endpoint, demonstrating statistically significant increases in time above threshold for absolute neutrophil counts (“TAT-ANC”) and time above threshold for absolute lymphocyte counts (“TAT-ALC”) in participants treated with mavorixafor versus placebo.
Added
As discussed further below, o n January 13, 2025, we entered into a License and Supply Agreement (the “Norgine Agreement”) with Norgine Pharma UK Limited (“Norgine”), pursuant to which Norgine is granted an exclusive license to distribute, market and sell our drug product for all indications in the European Economic Area, Switzerland, the United Kingdom, Australia and New Zealand.
Removed
Additional data showed that mavorixafor treatment resulted in statistically significant reductions in annualized infection rates versus placebo and clinically meaningful reductions in the both the severity and duration of infections versus placebo. Mavorixafor was generally well tolerated throughout the 52-week trial.
Added
In February 2025, we announced that we had entered into an agreement with taiba rare to distribute and commercialize XOLREMDI for the treatment of WHIM syndrome in select Middle East and North African countries. We continue to explore additional potential commercial and distribution opportunities in geographies where we may be able to efficiently leverage any of our regulatory approvals.
Removed
We are also currently advancing mavorixafor for the treatment of people with certain chronic neutropenic disorders following positive results from a Phase 1b clinical trial of a single dose of mavorixafor in people with idiopathic, cyclic, and congenital chronic neutropenia.
Added
The U.S. approval of XOLREMDI in the WHIM syndrome indication is the first for mavorixafor, which is an orally active, selective antagonist of chemokine receptor CXCR4, a key regulator of the movement of immune cells throughout the body.
Removed
We expect to share further data from the Phase 2 trial in the second quarter of 2024. Concurrent with conducting this Phase 2 trial, we are advancing our plans for a Phase 3 trial in the first half of 2024 of mavorixafor in people with certain chronic neutropenic disorders.
Added
In addition, when tested in combination with G-CSF, mavorixafor treatment enabled physicians to substantially reduce G-CSF dosing while maintaining normal mean ANC levels.
Removed
The planned 52-week, global Phase 3 trial is expected to be a 70 randomized, double-blinded, placebo-controlled trial assessing the safety and efficacy of mavorixafor, with or without concomitant G-CSF, in people with idiopathic or congenital neutropenia.
Added
Phase 3 Clinical Trial in Chronic Neutropenia We continue to progress our global, pivotal Phase 3 clinical trial, (the “4WARD” study) to evaluate the efficacy, safety, and tolerability of oral, once-daily mavorixafor (with or without stable doses of G-CSF) in people with congenital, acquired primary autoimmune, or idiopathic CN who are experiencing recurrent and/or serious infections.
Removed
If our development efforts for our product candidates are successful and result in regulatory approval, we may generate revenue in the future from product sales. We cannot predict if, when, or to what extent we will generate revenue from the commercialization and sale of our product candidates.
Added
The 52-week trial is a randomized, double-blind, placebo-controlled, multicenter study aiming to enroll 150 participants. We believe we are on track to complete enrollment in the 4WARD study in the third or fourth quarter of 2025.
Removed
We may never succeed in obtaining regulatory approval for any of our product candidates. Macroeconomic Considerations Unfavorable conditions in the economy in the United States and abroad may negatively affect the growth of our business and our results of operations. The effect of macroeconomic conditions may not be fully reflected in our results of operations until future periods.
Added
As part of the 2025 Restructuring, we implemented a net reduction of our employee headcount by 43 employees, or approximately 30% of our total workforce.
Removed
If, however, economic uncertainty increases or the global economy worsens, our business, financial condition and results of operations may be harmed.
Added
The strategic restructuring activities include (i) discontinuing of research efforts, (ii) closing of our facility in Vienna, Austria, (iii) pausing pre-clinical drug candidate programs, (iv) scaling the U.S. commercial field team and supporting roles across our business and (v) streamlining other spending to support the ongoing clinical development of mavorixafor for the larger population of those with chronic neutropenia.
Removed
The increase in research and development expenses in 2023 as compared to 2022 was primarily due to a $5.0 million development milestone payment under our Genzyme agreement, approximately $2 million of higher regulatory costs associated with the preparation and submission of our NDA, and additional consulting and temporary help across our research and development organization to support our NDA submission and our ongoing clinical trials.
Added
We estimate that the workforce reduction will be substantially completed in the first quarter of 2025. We estimate that it will incur charges of approximately $3.0 million for severance and other employee termination-related costs, primarily in the first quarter of 2025.
Removed
Selling, general and administrative expenses were $35.5 million in 2023, as compared to $27.0 million in 2022, reflecting an increase of $8.5 million.
Added
We expect the 2025 Restructuring will decrease annual spending by $30 to 35 million and believe it will have sufficient funds to support operations into the first half of 2026.
Removed
The increase in selling, general and administrative expenses in 2023 as compared to 2022 was primarily due to an increase in compensation expense due to in increase in head count, higher stock-based compensation costs and higher stock appreciation rights expense.
Added
The estimate of costs that we expect to incur related to the 2025 Restructuring as well as the decrease in annual spending, and the timing thereof are subject to a number of assumptions and actual results may differ.
Removed
We have added personnel to our marketing and sale operations organizations in anticipation of a potential commercial launch of our drug candidate in 2024. We have also incurred third party consulting costs associated with enabling our market access infrastructure.
Added
We may also incur additional costs not currently contemplated due to events that may occur as a result of, or that are associated with, the actions described for the 2025 Restructuring above.
Removed
We expect selling, general and administrative expenses will grow in the future as we continue to build out our selling, general and administrative functions. Goodwill Impairment Goodwill is tested quantitatively for impairment at the reporting unit level annually in the fourth quarter, or more frequently when events or changes in circumstances indicate that the asset might be impaired.
Added
Norgine Agreement On January 13, 2025, we entered into the Norgine Agreement, pursuant to which Norgine is granted an exclusive license to distribute, market and sell our product mavorixafor for all indications in the European Economic Area, Switzerland, the United Kingdom, Australia and New Zealand following regulatory approval.
Removed
Examples of such events or circumstances include, but are not limited to, a significant adverse change in legal or business climate, an adverse regulatory action or unanticipated competition or when our market value, measured as the price of our common stock multiplied by shares outstanding drops below the value of our net assets.
Added
Pursuant to the terms of the Norgine Agreement, we received an upfront payment of €28.5 million upon signing of the agreement and could receive up to €226.0 million upon the achievement of certain regulatory, commercial and sales milestones. We will also receive escalating, double-digit royalties of up to mid-twenties on any future net sales of our drug product by Norgine.
Removed
We have determined that our company operates in a single operating segment and has a single reporting unit. To perform the quantitative test, we compare the fair value of the reporting unit to its carrying value.
Added
Norgine will be responsible for all market access and commercialization activities and will eventually hold all marketing authorizations in the licensed territories.
Removed
As we have one reporting unit, we determine its fair value based on the market approach taking into consideration the market value of the company as a whole and any control premium that might be realized upon the sale of the reporting unit.
Added
We will manufacture and supply drug product to Norgine for a supply price derived from our product manufacturing cost plus a low double-teen digit margin. 67 Results of Operations Comparison of the Years Ended December 31, 2024 and 2023 The following table summarizes the results of our operations for the periods indicated: Year Ended December 31, 2024 2023 Change (in thousands) Product revenue, net $ 2,557 $ — $ 2,557 Costs and operating expenses: Cost of revenue 797 — 797 Research and development 81,643 72,017 9,626 Selling, general and administrative 61,518 35,505 26,013 Gain on sale of non-financial asset (105,000) — (105,000) Total operating expenses 38,958 107,522 (68,564) Loss from operations (36,401) (107,522) 71,121 Total other (expense) income, net (739) 6,433 (7,172) Loss before provision for income taxes (37,140) (101,089) 63,949 Provision for income taxes 310 78 232 Net loss $ (37,450) $ (101,167) $ 63,717 Product Revenue, Net Net revenue from the sale of our drug product was $2.6 million for the year ended December 31, 2024.

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