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What changed in Inmune Bio, Inc.'s 10-K — 2023 vs 2024

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Paragraph-level year-over-year comparison of Inmune Bio, 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.

+377 added−386 removedSource: 10-K (2024-12-31) vs 10-K (2024-03-28)

Top changes in Inmune Bio, Inc.'s 2024 10-K

377 paragraphs added · 386 removed · 209 edited across 4 sections

Item 1. Business

Business — how the company describes what it does

106 edited+40 added−75 removed232 unchanged
Biggest changeThe overall principal components of our business strategy to achieve these objectives are to: ● pursue development strategies and regulatory approval pathways that allow us to expand the treatment of oncology patients with our lead product candidate INKmune; ● pursue pre-clinical development strategies to facilitate out-licensing INB03; ● pursue development strategies and regulatory approval pathways that allow the treatment of neurodegenerative diseases in patients with our lead product candidate, XPro; ● Pursue development strategies with a dominant-negative tumor necrosis factor (“DN-TNF”) compound for the treatment of DMD; ● adopt a product development strategy that solidifies our existing intellectual property (“IP”) to prevent competition and expand our IP suite into related immunotherapeutic areas; ● provide clear value propositions to third-party payers, such as managed care companies or government programs like Medicare, to merit reimbursement for our product candidates; and ● Collaborate with other pharmaceutical companies with respect to, among other things, our INKmune and the DN-TNF platform that includes INB03 and XPro product candidates, our DMD DN-TNF candidate and other products that will benefit from development or marketing beyond our current resources.
Biggest changeThe overall principal components of our business strategy to achieve these objectives are to: ● Pursue a registration strategy for CORDStrom in RDEB that maximizes the value of the therapy and expand the CORDStrom platform; ● Pursue development strategies and regulatory approval pathways that allow the treatment of neurodegenerative diseases in patients with our lead product candidate, XPro; ● Pursue development strategies and regulatory approval pathways that allow the treatment cancer with our lead oncology platform, INKmune; ● Adopt a product development strategy that solidifies our existing intellectual property (“IP”) to prevent competition and expand our IP suite into related immunotherapeutic areas; ● Provide clear value propositions to third-party payers, such as managed care companies or government programs like Medicare, to merit reimbursement for our product candidates; and ● Collaborate with other pharmaceutical companies with respect to, among other things, our XPro, CORDStrom and INKmune product platforms.
His blood NK cells responded in differentiation into mlNK as hoped but it is too early to determine if INKmune has provide any clinical benefit. Due to market opportunities, the Company has closed the high-risk MDS trial to focus on solid tumors.
His blood NK cells responded in differentiation into mlNK as hoped but it is too early to determine if INKmune has provide any clinical benefit. Due to market opportunities, the Company closed the high-risk MDS trial to focus on solid tumors.
To our knowledge, there are no innate immune check-point inhibitors in development that have the unique characteristics of INB03 that neutralize sTNF to: i) decreases the proliferation of MDSC; ii) decreasing local and systemic immunosuppression caused by MDSC by stopping production of immunosuppressive cytokines and iii) improving NK/DC cross-talk to recruit the adaptive immune system to fight the cancer. 19 Intellectual Property We seek to protect our therapeutic programs by continuously developing patent properties covering novel compositions, formulations, purpose-limited compositions, combination treatments, methods of medical treatment, and other inventions, whether created internally or in-licensed, in the United States Patent & Trademark Office (the “USPTO”), the World Intellectual Property Organization (“WIPO”) under the Patent Cooperation Treaty (“PCT”), and in patent offices for various foreign jurisdictions.
To our knowledge, there are no innate immune check-point inhibitors in development that have the unique characteristics of INB03 that neutralize sTNF to: i) decreases the proliferation of MDSC; ii) decreasing local and systemic immunosuppression caused by MDSC by stopping production of immunosuppressive cytokines and iii) improving NK/DC cross-talk to recruit the adaptive immune system to fight the cancer. 16 Intellectual Property We seek to protect our therapeutic programs by continuously developing patent properties covering novel compositions, formulations, purpose-limited compositions, combination treatments, methods of medical treatment, and other inventions, whether created internally or in-licensed, in the United States Patent & Trademark Office (the “USPTO”), the World Intellectual Property Organization (“WIPO”) under the Patent Cooperation Treaty (“PCT”), and in patent offices for various foreign jurisdictions.
Finally, the patient has had a significant clinical improvement with a reduction of his ECOG score from 2 to 0 and a significant reduction in blood product support. Three compassionate use cases have also been treated. Two were young patients with AML who had failed previous hematopoietic stem cell transplants (“HSCT”).
Finally, the patient had a significant clinical improvement with a reduction of his ECOG score from 2 to 0 and a significant reduction in blood product support. Three compassionate use cases have also been treated. Two were young patients with AML who had failed previous hematopoietic stem cell transplants (“HSCT”).
The Company engaged KBI Biopharma to manufacture 6 lots of XPro/INB03 at the Boulder, Colorado facility using the original master cell bank and updated manufacturing process. One lot has been converted into drug product using the US fill/finish facility of Vetter Pharma.
The Company engaged KBI Biopharma to manufacture 6 lots of XPro at the Boulder, Colorado facility using the original master cell bank and updated manufacturing process. One lot has been converted into drug product using the US fill/finish facility of Vetter Pharma.
Licensor may terminate the PITT Agreement upon written notice if: (i) the Company defaults as to performance of material obligations which have not been cured within 60 days after receiving written notice; or (ii) the Company ceases to carry out its business, becomes bankrupt or insolvent, applies for or consents to the appointment of a trustee, receiver or liquidator of its assets or seeks relief under any law for the aid of debtors. 22 Xencor License Agreement On October 3, 2017, the Company entered into a license agreement with Xencor, Inc.
Licensor may terminate the PITT Agreement upon written notice if: (i) the Company defaults as to performance of material obligations which have not been cured within 60 days after receiving written notice; or (ii) the Company ceases to carry out its business, becomes bankrupt or insolvent, applies for or consents to the appointment of a trustee, receiver or liquidator of its assets or seeks relief under any law for the aid of debtors. 19 Xencor License Agreement On October 3, 2017, the Company entered into a license agreement with Xencor, Inc.
Additionally, either party may terminate the agreement on 30 days prior written notice to the other if that other party materially breach any term of the agreement and such breaches (to the extent it is remediable) is not remedied within 30 days of the written request to the other party to do so. 24 Challenges in the Market for Immunotherapy Products Government Regulation The FDA and other federal, state, local and foreign regulatory agencies impose substantial requirements upon the clinical development, approval, labeling, manufacture, marketing, and distribution of drug products.
Additionally, either party may terminate the agreement on 30 days prior written notice to the other if that other party materially breach any term of the agreement and such breaches (to the extent it is remediable) is not remedied within 30 days of the written request to the other party to do so. 21 Challenges in the Market for Immunotherapy Products Government Regulation The FDA and other federal, state, local and foreign regulatory agencies impose substantial requirements upon the clinical development, approval, labeling, manufacture, marketing, and distribution of drug products.
In addition, certain states have their own laws that govern the privacy and security of health information in certain circumstances, many of which differ from each other and/or HIPAA in significant ways and may not have the same effect, thus complicating compliance efforts. 30 Coverage and Reimbursement Sales of pharmaceutical products depend significantly on the extent to which coverage and adequate reimbursement are provided by third-party payors.
In addition, certain states have their own laws that govern the privacy and security of health information in certain circumstances, many of which differ from each other and/or HIPAA in significant ways and may not have the same effect, thus complicating compliance efforts. 27 Coverage and Reimbursement Sales of pharmaceutical products depend significantly on the extent to which coverage and adequate reimbursement are provided by third-party payors.
(Biol Blood Marrow Transplant. 2018 Mar 26. pii: S1083-8791(18)30132-0. doi: 10.1016/j.bbmt.2018.03.019.) The results of the laboratory and Phase I studies provide evidence that our strategy for treating residual disease is sensible but unproven. 14 Because INKmune primes NK cells to target naturally occurring antigens, we believe INKmune can be used in to treat a wide variety of cancers including hematologic malignancy (AML, MM, CML, high risk MDS) and solid tumors (renal, prostate, breast, ovarian, pancreas and lung).
(Biol Blood Marrow Transplant. 2018 Mar 26. pii: S1083-8791(18)30132-0. doi: 10.1016/j.bbmt.2018.03.019.) The results of the laboratory and Phase I studies provide evidence that our strategy for treating residual disease is sensible but unproven. 11 Because INKmune primes NK cells to target naturally occurring antigens, we believe INKmune can be used to treat a wide variety of cancers including hematologic malignancy (AML, MM, CML, high risk MDS) and solid tumors (renal, prostate, breast, ovarian, pancreas and lung).
These include accelerated approval under Subpart H of the agency’s NDA approval regulations, fast track drug development procedures and priority review. 25 The United States, European Union and other jurisdictions may grant orphan drug designation to drugs intended to treat a “rare disease or condition,” which, in the United States, is generally a disease or condition that affects no more than 200,000 individuals.
These include accelerated approval under Subpart H of the agency’s NDA approval regulations, fast track drug development procedures and priority review. 22 The United States, European Union and other jurisdictions may grant orphan drug designation to drugs intended to treat a “rare disease or condition,” which, in the United States, is generally a disease or condition that affects no more than 200,000 individuals.
Many states have similar laws that apply to their state health care programs as well as private payors. 29 Federal false claims and false statement laws, including the federal civil False Claims Act, or FCA, imposes liability on persons or entities that, among other things, knowingly present or cause to be presented claims that are false or fraudulent or not provided as claimed for payment or approval by a federal health care program.
Many states have similar laws that apply to their state health care programs as well as private payors. 26 Federal false claims and false statement laws, including the federal civil False Claims Act, or FCA, imposes liability on persons or entities that, among other things, knowingly present or cause to be presented claims that are false or fraudulent or not provided as claimed for payment or approval by a federal health care program.
However, this designation provides an exemption from marketing and authorization (NDA) fees. We plan to follow a similar path with INB03 or XPro, although the precise indication cannot be determined until we are farther along in the development process. Clinical Trials Phase 1 clinical trials typically involve the initial introduction of the product candidate into healthy human volunteers.
However, this designation provides an exemption from marketing and authorization (“NDA”) fees. We plan to follow a similar path with INB03 or XPro, although the precise indication cannot be determined until we are farther along in the development process. Clinical Trials Phase 1 clinical trials typically involve the initial introduction of the product candidate into healthy human volunteers.
The Company reported preliminary data on July 13, 2020 and January 21, 2021 supporting the use of XPro to decrease neuroinflammation in patients with Alzheimer’s disease and biomarkers of peripheral inflammation (see above). We completed enrollment of patients into an open label, biomarker directed, Phase I clinical trial in AUS that approaches AD as an immunologic disease.
The Company reported preliminary data on July 13, 2020 and January 21, 2021 supporting the use of XPro to decrease neuroinflammation in patients with Alzheimer’s disease and biomarkers of peripheral inflammation (see above). We completed enrollment of patients into an open label, biomarker directed, Phase I clinical trial in Australia that approaches AD as an immunologic disease.
The open label, dose escalation trial in patients with Alzheimer’s disease with biomarkers of peripheral inflammation (one of CRP>1.5mg/L, HgbA1c>6.0, ESR>10sec or have ApoE4) treats the patients with XPro as a once-a-week subcutaneous injection for 3 months. AD patients with one biomarker of inflammation are classified as having AD with neuroinflammation (ADi).
The open label, dose escalation trial in patients with Alzheimer’s disease with biomarkers of peripheral inflammation (one of CRP>1.5mg/L, HgbA1c>6.0, ESR>10sec or have ApoE4) treats the patients with XPro as a once-a-week subcutaneous injection for 3 months. AD patients with one biomarker of inflammation are classified as having AD with neuroinflammation (“Adi”).
We plan to use a combination of publication, presentation and investor relations to discuss INKmune and INB03 and to educate the clinical, biopharma and investor community on the value of these novel therapeutic approaches. 17 DN-TNF Competition To our knowledge, there are no other companies developing a therapy to treat patients with MUC4+HER2+ tumors.
We plan to use a combination of publication, presentation and investor relations to discuss INKmune and INB03 and to educate the clinical, biopharma and investor community on the value of these novel therapeutic approaches. 14 DN-TNF Competition To our knowledge, there are no other companies developing a therapy to treat patients with MUC4+HER2+ tumors.
In consideration for the INKmune License, we are obligated to pay Immune Ventures certain milestone and royalty payments. 21 The term of the Immune Ventures Agreement began on October 29, 2015, and, if not terminated sooner pursuant to the agreement, ends on a country-by-country basis on the date of the expiration of the last to expire patent rights where patent rights exist.
In consideration for the INKmune License, we are obligated to pay Immune Ventures certain milestone and royalty payments. 18 The term of the Immune Ventures Agreement began on October 29, 2015, and, if not terminated sooner pursuant to the agreement, ends on a country-by-country basis on the date of the expiration of the last to expire patent rights where patent rights exist.
The Company is following the developments in this area closely. The Company believes the anti-amyloid therapies will slowly develop market share, but due to their safety and efficacy profile, there will be demand for safer and more efficacious therapies that do not target amyloid. 27 Clinical testing must satisfy extensive FDA regulations.
The Company is following the developments in this area closely. The Company believes the anti-amyloid therapies will slowly develop market share, but due to their safety and efficacy profile, there will be demand for safer and more efficacious therapies that do not target amyloid. 24 Clinical testing must satisfy extensive FDA regulations.
Other venues such as Europe, Canada, Japan and other Pacific Rim countries may be included in the development program in the future. 26 The INB03 Phase I trial has been completed and provided evidence of safety and a pharmacodynamic drug affect, decrease of inflammatory biomarkers, needed to move the program to a Phase II clinical trial in cancer.
Other venues such as Europe, Canada, Japan and other Pacific Rim countries may be included in the development program in the future. 23 The INB03 Phase I trial has been completed and provided evidence of safety and a pharmacodynamic drug affect, decrease of inflammatory biomarkers, needed to move the program to a Phase II clinical trial in cancer.
If our future suppliers are not able to comply with these requirements, the FDA may, among other things, halt our clinical trials, require us to recall a product from distribution, or withdraw approval of the product. 28 The FDA may withdraw approval if compliance with regulatory requirements and standards is not maintained or if problems occur after the product reaches the market.
If our future suppliers are not able to comply with these requirements, the FDA may, among other things, halt our clinical trials, require us to recall a product from distribution, or withdraw approval of the product. 25 The FDA may withdraw approval if compliance with regulatory requirements and standards is not maintained or if problems occur after the product reaches the market.
Because this is a simple subcutaneous injection similar to an insulin injection (the therapy patients give themselves for treatment of Type 1 diabetes mellitus), we expect patients to administer the therapy by themselves or caregivers and not require expensive or logistically challenging clinic visits to receive the therapy. 9 Release of INB03 and XPro drug supply GMP DN-TNF product (INB03 and XPro) used in the oncology Phase I, AD Phase I and COVID-19 Phase II trial were manufactured by Lonza at a site in New Hampshire.
Because this is a simple subcutaneous injection similar to an insulin injection (the therapy patients give themselves for treatment of Type 1 diabetes mellitus), we expect patients to administer the therapy by themselves or caregivers and not require expensive or logistically challenging clinic visits to receive the therapy. 7 Release of XPro drug supply GMP DN-TNF product (XPro) used in the oncology Phase I, AD Phase I and COVID-19 Phase II trial were manufactured by Lonza at a site in New Hampshire.
We have not yet had a discussion with the Medicines and Healthcare Products Regulatory Agency (“MHRA”) and/or FDA regarding such designation, but plan to do so in the future. We believe the INKmune program to treat castration resistant prostate cancer may qualify for orphan status.
We have not yet had a discussion with the United Kingdom Medicines and Healthcare Products Regulatory Agency (“MHRA”) and/or FDA regarding such designation, but plan to do so in the future. We believe the INKmune program to treat castration resistant prostate cancer may qualify for orphan status.
The proteome also demonstrated a clear dose response with a greater number of proteins being affected by the target dose compared to low dose XPro therapy (0.3 vs 1.0 mg/kg/week for 12 weeks) (Figure AD3). The CSF proteome data is only partially analyzed.
The proteome also demonstrated a clear dose response with a greater number of proteins being affected by the target dose compared to low dose XPro therapy (0.3 vs 1.0 mg/kg/week for 12 weeks) (Figure below). The CSF proteome data is only partially analyzed.
Half of the first lot is frozen as drug substance at -80C with a plan to convert to drug product as clinical supplies are needed to support the AD and TRD Phase II trials in May 2024. The unfrozen drug product is being used in the ongoing AD02 AD trial.
Half of the first lot is frozen as drug substance at -80C with a plan to convert to drug product as clinical supplies are needed to support the AD and TRD Phase II trials. The unfrozen drug product is being used in the ongoing AD02 AD trial.
We have an active partnering position as it relates to XPro development in neurodegenerative and neuropsychiatric diseases, although limited partnering discussion are underway at this time. There are two partnering opportunities with this novel immunotherapy for the treatment of neurologic and psychiatric diseases.
We have an active partnering position as it relates to XPro development in neurodegenerative and neuropsychiatric diseases, although limited partnering discussions are underway at this time. There are two partnering opportunities with this novel immunotherapy for the treatment of neurologic and psychiatric diseases.
Companies in the personalized immune-oncology business; and 3. Companies in the precision immuno-oncology business. 18 We are not aware of any approved treatments that are classified as NK cell therapies. We are aware of public companies in the NK cell therapy business such as Century Therapeutics, Immunity Bio, Nkarta, Fate Therapeutics, Glycostem and others.
Companies in the personalized immune-oncology business; and 3. Companies in the precision immuno-oncology business. 15 We are not aware of any approved treatments that are classified as NK cell therapies. We are aware of public companies in the NK cell therapy business such as Century Therapeutics, Immunity Bio, Nkarta, Fate Therapeutics, Glycostem and others.
The remainder of the original fermentation runs is frozen as a cell paste with a plan to process to drug substance. The company expects to convert the drug substance to drug product 1H25. Downstream processing to drug product and fill/finish to drug product of the cell paste will occur in 2025 as needed to support the clinical trials.
The remainder of the original fermentation runs is frozen as a cell paste with a plan to process to drug substance. The company expects to convert the drug substance to drug product during 2025. Downstream processing to drug product and fill/finish to drug product of the cell paste will occur in 2025 as needed to support the clinical trials.
In the setting of AD, microglial activation causes dendritic pruning, synaptic dysfunction and nerve cell death that contributes to cognitive decline and the behavioral manifestations of AD including depression, aggressiveness, sleep disorders, hallucinations and anhedonia. Elimination of microglial activation should reverse these symptoms.
In the setting of AD, microglial activation causes synaptic dysfunction and nerve cell death that contributes to cognitive decline and the behavioral manifestations of AD including depression, aggressiveness, sleep disorders, hallucinations and anhedonia. Elimination of microglial activation should reverse these symptoms.
These companies are developing products that involve replacing or supplementing NK cells of the patient for the treatment cancer. Their product requires extensive ex-vivo cell manipulations which, with respect to Century Therapeutics and Fate Therapeutics, may include gene therapy. The next larger group of companies are in the personalized immuno-oncology business with products focused on T cell activation strategies.
These companies are developing products that involve replacing or supplementing NK cells of the patient for the treatment cancer. Their products require extensive ex-vivo cell manipulations which, with respect to Century Therapeutics and Fate Therapeutics, may include gene therapy. The next larger group of companies are in the personalized immuno-oncology business with products focused on T cell activation strategies.
We believe that we have developed a way to manufacture human mesenchymal stromal cells for the medical research and biotech community that offers large volumes of high-quality, low passage human umbilical cord mesenchymal stromal cells with minimal batch-to-batch variability.
We believe that we have developed a way to manufacture human mesenchymal stromal cells for the medical research and biotech community that offers large volumes of high-quality, human umbilical cord mesenchymal stromal cells with minimal batch-to-batch variability.
We have established a reliable supply of human umbilical cords based on our agreement with the Anthony Nolan Cord Blood Bank in the United Kingdom and may seek additional supplies from US sources in the future. We have developed a validated manufacturing process that reliably produces clinical grade (“cGMP”) quality mesenchymal stromal cells that we call CORDstrom.
We have established a reliable supply of human umbilical cords based on our agreement with the Anthony Nolan Cord Blood Bank in the United Kingdom and plan to seek additional supplies from US sources in the future. We have developed a validated manufacturing process that reliably produces clinical grade (“cGMP”) quality mesenchymal stromal cells that we call CORDStrom.
An investigator-initiated trial performed at the Royal Free Hospital in London 2009 was funded by a UK charity. Fifteen patients with relapsed, high-risk AML were enrolled in the trial. Because of drop-out due to disease progression, delays in product production and complications of conditioning therapy, only 7 of the fifteen patients were treated with the TpNK cell product.
An investigator-initiated trial performed at the Royal Free Hospital in London 2009 was funded by a United Kingdom charity. Fifteen patients with relapsed, high-risk AML were enrolled in the trial. Because of drop-out due to disease progression, delays in product production and complications of conditioning therapy, only 7 of the fifteen patients were treated with the TpNK cell product.
All manufacturing has been under the direction of Professor Mark Lowdell. The Company can produce enough INKmune to complete its Phase I clinical trial in men with metastatic castrate resistant prostate cancer (mCRPC)..
All manufacturing has been under the direction of Professor Mark Lowdell. The Company can produce enough INKmune to complete its Phase I clinical trial in men with metastatic castrate resistant prostate cancer (“mCRPC”).
Early analysis of the data focusing on 26 AD related proteins demonstrated changes in inflammation, neuronal and synaptic proteins caused by decreasing neuroinflammation after treatment with XPro (Figure AD2).
Early analysis of the data focusing on 26 AD related proteins demonstrated changes in inflammation, neuronal and synaptic proteins caused by decreasing neuroinflammation after treatment with XPro (Figure below).
Because of different mechanism of action of XPro compared to the non-selective TNF inhibitors, we expect a lower risk of immunosuppression and demyelinating complications such as multiple sclerosis (MS).
Because of different mechanism of action of XPro compared to the non-selective TNF inhibitors, we expect a lower risk of immunosuppression and demyelinating complications such as multiple sclerosis (“MS”).
Therapies for Alzheimer’s disease are needed for medical, societal and economic reasons. The cost of Alzheimer’s disease to the government is large and growing. Recently approved therapies that target amyloid have a modest impact on disease progression and are difficult to use due to side-effects in some patients.
Additional therapies are need for treatment of Alzheimer’s disease are needed for medical, societal and economic reasons. The cost of Alzheimer’s disease to the government is large and growing. Recently approved therapies that target amyloid have a modest impact on disease progression and are difficult to use due to side-effects in some patients.
The regulatory path for therapeutic applications of the mesenchymal stem cell products is well established and similar to the regulatory approval process for other cell therapies. We will only be responsible for regulatory compliance related to manufacturing of the mesenchymal stromal cells when the product is being developed by a third party.
The regulatory path for therapeutic applications of the mesenchymal stem/stromal cell products is well established and similar to the regulatory approval process for other cellular medicines. We will only be responsible for regulatory compliance related to manufacturing of the mesenchymal stromal cells when the product is being developed by a third party.
(Figure 1 below). 13 The ability of NK cells to kill tumor cells depends on the strength and duration of the cell-cell interaction. This is called avidity. The higher the avidity the greater the tumor cell killing.
(Figure 1 below). 10 The ability of NK cells to kill tumor cells depends on the strength and duration of the cell-cell interaction. This is called avidity. The higher the avidity the greater the tumor cell killing.
The primary end-point is Early/Mild Alzheimer’s Cognitive Composite (EMACC), a sensitive cognitive end-point validated for use in patients with early AD. Secondary cognitive (ADAS-Cog13, CDR-SB and NPI) and functional (GAS, ADCS-ADL) end-points will be measured. Exploratory structural and function biomarkers of brain function and structural integrity using EEG and MRI DTI will be used in some or all patients.
The primary end-point is Early/Mild Alzheimer’s Cognitive Composite (“EMACC”), a sensitive cognitive end-point validated for use in patients with early AD. Secondary cognitive (CDR-SB and NPI) and functional (GAS, ADCS-ADL) end-points will be measured. Exploratory structural and function biomarkers of brain function and structural integrity using EEG and MRI DTI will be used in some or all patients.
In the U.S., this includes Orphan Drug Designation and expedited programs for approval including Accelerated Approval, Breakthrough Therapy Designation, Fast Track Designation, and priority review (see “Government Regulation). We cannot predict which, if any, of these programs we will benefit from without further discussions with the FDA, EMA and other competent regulatory authorities.
In the U.S., this includes Orphan Drug Designation and expedited programs for approval including Accelerated Approval, Breakthrough Therapy Designation, Fast Track Designation, and priority review (see the section entitled “Government Regulation”). We cannot predict which, if any, of these programs we will benefit from without further discussions with the FDA, EMA and other competent regulatory authorities.
We believe the use of INKmune and/or INB03 in patients with a high risk of tumor progression and death from tumor should prolong survival, improve the patient’s quality of life and decrease the total cost of care for patients with these lethal malignancies. For example, cancer patients relapse frequently. Each relapse requires a complex treatment regimen that has decreasing benefits.
We believe the use of INKmune patients with a high risk of tumor progression and death from tumor should safely prolong survival, improve the patient’s quality of life and decrease the total cost of care for patients with these lethal malignancies. For example, cancer patients relapse frequently. Each relapse requires a complex treatment regimen that has decreasing benefits.
The supply of Lonza DN-TNF product is limited but allowed completion of the Phase I study in Alzheimer’s disease and support of patients in the extension study for 12 months. New batches of XPro have been produced to support future clinical trials.
The supply of Lonza DN-TNF product is limited but allowed completion of the Phase I study in Alzheimer’s disease and support of patients in the extension study for 12 months. New batches of XPro have been produced for ongoing clinical trials.
While each invention is unique and territories for protection are decided on a case-by-case basis, we generally pursue patents in Australia, Canada, Europe, Japan, and the United States, and sometimes in Brazil, China and/or Korea. We currently have in our portfolio fifteen (15) issued patents and twenty-three (23) pending patent applications, including both company-owned and in-licensed properties.
While each invention is unique and territories for protection are decided on a case-by-case basis, we generally pursue patents in Australia, Canada, Europe, Japan, and the United States, and sometimes in Brazil, China and/or Korea. We currently have in our portfolio fifteen (15) issued patents and thirty (30) pending patent applications, including both company-owned and in-licensed properties.
We believe there are two reasons for us to enter collaborations with other companies. The first is the further development of INKmune, INB03, XPro and DN-TNF by either providing additional innovations to the product, including combination therapy strategies, and/or providing resources to improve the speed and breadth of the development process.
We believe there are two reasons for us to enter collaborations with other companies. The first is the further development of INKmune, XPro and CORDStrom by either providing additional innovations to the product, including combination therapy strategies, and/or providing resources to improve the speed and breadth of the development process.
Patients in the 10mg/kg group were offered extended use of the drug for up to 12 months. Three patients remained on XPro for 12 months. Preliminary data was presented in a webinar on 13 July 2020.
Patients in the 1.0mg/kg group were offered extended use of the drug for up to 12 months. Three patients remained on XPro for 12 months. Preliminary data was presented in a webinar on 13 July 2020.
The goal of the Phase II trial will be to demonstrate the prolonged control of neuroinflammation in patients with dementia will help control cognitive decline. 7 The Phase I trial enrolled 18 patients at doses of 0.3, 0.6 and 1.0mg/kg given once a week as subcutaneous injection for three months.
The goal of the Phase II trial will be to demonstrate the prolonged control of neuroinflammation in patients with dementia will help control cognitive decline. 5 The Phase I trial enrolled 18 patients at three dose cohorts of 0.3, 0.6 and 1.0mg/kg given once a week as subcutaneous injection for three months.
The HucMSC product produced in this facility are fully qualified to be used for either research or clinical trials. We have developed a validated manufacturing process that reliably produces contract manufacturer of the clinical grade (“cGMP”) quality mesenchymal stem cells that we call CORDstrom. To date, we are supporting two academic clinical trials with CORDstrom.
The HucMSC product produced in this facility are fully qualified to be used for either research or clinical trials. We have developed a validated manufacturing process that reliably produces contract manufacturer of the clinical grade (“cGMP”) quality mesenchymal stem cells that we call CORDStrom.
Pursue development and regulatory approval pathways. We believe INKmune, INB03 and XPro may be approvable under pathways that are potentially shorter than those typically available for drug products based on novel active ingredients, including as an orphan drug under the Orphan Drug Act and approval under the Food and Drug Administration (the “FDA”) Accelerated Approval Program (see “Government Regulation”).
We believe INKmune and XPro may be approvable under pathways that are potentially shorter than those typically available for drug products based on novel active ingredients, including as an orphan drug under the Orphan Drug Act and approval under the Food and Drug Administration (the “FDA”) Accelerated Approval Program (see the section entitled “Government Regulation”).
Substantial indirect data supports use of XPro in humans including a decreased risk of AD in patients treated with non-selective TNF inhibitors for rheumatoid arthritis and treatment using direct injection into paraspinous venous plexus.
Substantial pre-clinical data supports the use of XPro in murine models of AD. Substantial indirect data supports use of XPro in humans including a decreased risk of AD in patients treated with non-selective TNF inhibitors for rheumatoid arthritis and treatment using direct injection into paraspinous venous plexus.
Once third of TRD patients have peripheral biomarkers to inflammation (elevated CRP). This is a large patient population. The role of TNF and anti-TNF therapeutics was explored in a small open label clinical trial by Prof. Andrew Miller, MD of Emory University whereby it was demonstrated that patients which have elevated TNF levels responded to treatment with infliximab (Miller, 2011).
This is a large patient population. The role of TNF and anti-TNF therapeutics was explored in a small open label clinical trial by Prof. Andrew Miller, MD of Emory University whereby it was demonstrated that patients which have elevated TNF levels responded to treatment with infliximab (Miller, 2011).
The Company plans to put all of its INKmune development efforts into the on-going US Phase I/II trial in men with mCRPC. 16 INKmune Registration Studies and/or Partnering During March 2023 the Company opened an Investigational New Drug (“IND”) application for a Phase I/II trial of INKmune in metastatic castrate resistant prostate cancer (mCPRC).
The Company plans to put all of its INKmune development efforts into the on-going US Phase I/II trial in men with mCRPC. 13 INKmune Registration Studies and/or Partnering During March 2023 the Company opened an Investigational New Drug (“IND”) application for a Phase I/II trial of INKmune in mCPRC.
The following table summarizes current IP covering our DN-TNF Platform Technology: Subject Matter / Compound # Pending Applications # Issued Patents Geographical Scope Nominal Patent Term DNTNF compositions and formulations 2 0 global 2024-2044 Use of DNTNF for treating disease 39 9 global 2033-2041 INB-16 / INKmune (Oncology) INKmune is a replication-incompetent derivative of our proprietary INB-16 cell line.
The following table summarizes current IP covering our DN-TNF platform technology: Subject Matter / Compound # Pending Applications # Issued Patents Geographical Scope Nominal Patent Term DNTNF compositions and formulations 2 0 global 2044-2045 Use of DNTNF for treating disease 19 10 global 2033-2041 DNTNF manufacturing/CMC 1 0 global 2045 INB-16 / INKmune (Oncology) INKmune is a replication-incompetent derivative of our proprietary INB-16 cell line.
Additional data may result from these ongoing analytics. 8 The results of the Phase I study demonstrated that XPro safely decreases neuroinflammation in patients with ADi who have biomarkers of peripheral inflammation or are ApoE4 positive when given for at least 3 months at the 1mg/kg once a week dose.
Additional data may result from these ongoing analytics. 6 The results of the Phase I study demonstrated that XPro safely decreases neuroinflammation in patients with AD and elevated neuroinflammation with biomarkers of peripheral inflammation or are ApoE4 positive when given for at least 3 months at the 1mg/kg once a week dose.
The most popular are the CAR-T cell therapies which are a patient specific ex-vivo gene therapy approach to a single disease (for example: pediatric ALL). CAR-T therapy has become wildly popular of late and includes many private companies, newer public companies such as Bluebird, Juno Therapeutics and Mustang Bio as well as established companies such as Novartis and Gilead.
The most popular are the CAR-T cell therapies which are a patient specific ex-vivo gene therapy approach. CAR-T therapy has become wildly popular of late and includes many private companies, public companies such as Bluebird, Juno Therapeutics and Mustang Bio as well as established companies such as Novartis and Gilead.
The following table summarizes current IP covering INB-16 / INKmune: Subject Matter / Compound # Pending Applications # Issued Patents Geographical Scope Nominal Patent Term INB-16 / INKmune compositions 1 0 global 2036-2043 Use of INKmune for treating disease 2 6 global 2036-2043 20 General IP Disclosures Our commercial success depends in part on obtaining and maintaining patent and trade secret protections, where applicable, of our current and future product candidates and the methods used to manufacture them, as well as successfully defending our patents against third-party challenges.
The following table summarizes current IP covering our CORDStrom platform technology: Subject Matter / Compound # Pending Applications # Issued Patents Geographical Scope Nominal Patent Term CORDStrom compositions and formulations 1 0 global 2045 Use of CORDStrom for treating disease 1 0 global 2045 General IP Disclosures Our commercial success depends in part on obtaining and maintaining patent and trade secret protections, where applicable, of our current and future product candidates and the methods used to manufacture them, as well as successfully defending our patents against third-party challenges.
The Company received approval to initiate the Phase I trial with XPro in patients with Alzheimer’s disease in May 2019 and received authorization to start the Phase II trial in patients with mild AD on January 5, 2022.
The second interaction with the regulatory body occurred in March 2019. The Company received approval to initiate the Phase I trial with XPro in patients with Alzheimer’s disease in May 2019 and received authorization to start the Phase II trial in patients with mild AD on January 5, 2022.
Additional data was presented on January 21, 2021CSF cytokine/chemokines were measured in 9 patients before and after 12 weeks of weekly therapy with XPro using a panel from OLINK Target 48 Cytokine (https://www.olink.com/products/olink-target-48-cytokine/), that measures 45 (Figure AD1).
Additional data was presented on January 21, 2021CSF cytokine/chemokines were measured in 9 patients before and after 12 weeks of weekly therapy with XPro using a panel from OLINK Target 48 Cytokine (Figure below).
Mark Lowdell’s research group developed and validated a methodology for producing large numbers of clinical-grade pooled human umbilical cord derived mesenchymal stem cells (“HucMSC”). We believe we are well positioned to become a preferred manufacturing partner for companies who need MSC for clinical programs.
Mark Lowdell’s research group developed and validated a methodology for producing large numbers of clinical-grade pooled HucMSC. We believe we are well positioned to become a preferred manufacturing partner for companies who need MSC for clinical programs.
As consideration under the PITT Agreement, we are obligated to pay: (i) annual maintenance fees, (ii) royalty payments based on the sale of products making use of the licensed technology, and (iii) milestone payments. In 2022, the Company paid $5,000 according to the PITT Agreement as an annual maintenance fee.
As consideration under the PITT Agreement, we are obligated to pay: (i) annual maintenance fees, (ii) royalty payments based on the sale of products making use of the licensed technology, and (iii) milestone payments.
By way of example, in August 2022, the Inflation Reduction Act of 2022, or the IRA, was signed into law.
In August 2022, the Inflation Reduction Act of 2022 (IRA) was signed into law.
We believe ADi is not the only indication for XPro in neurodegenerative and neuropsychiatric diseases. We plan to pursue other indications in neurodegenerative diseases as resources become available. We have received NIMH funding to support a Phase II TRD program that hopes to start patient enrollment in 2024.
We define ADi as Alzheimer’s disease with biomarkers of inflammation. We believe ADi is not the only indication for XPro in neurodegenerative and neuropsychiatric diseases. We plan to pursue other indications in neurodegenerative diseases as resources become available. We have received NIMH funding to support a Phase II TRD program that will start patient enrollment during 2025.
We are designing our clinical development programs to demonstrate compelling, competitive advantages to patients and prescribers, and to demonstrate value propositions to third-party payors.
Provide clear value propositions to third-party payors to merit reimbursement for our product candidates . We are designing our clinical development programs to demonstrate compelling, competitive advantages to patients and prescribers, and to demonstrate value propositions to third-party payors.
Based on preliminary data released on July 13, 2020, and January 21, 2021, we closed after completion of a 0.6mg/kg treatment group. We canceled plans to treat patients with 3.0mg/kg.
Based on preliminary data released on July 13, 2020, and January 21, 2021, we closed after completion of a 0.6mg/kg treatment group. We canceled plans to treat patients with 3.0mg/kg. The data from the Phase I trial informed the design of the Phase II trials described above.
The patient underwent intensive monitoring over 120 days. There are 4 observations from this first patient. The patient has dramatically increased the number of activated, “memory-like” NK cells in circulation. Memory-like NK cells (mlNK) are activated NK cells with a unique cell surface protein phenotype and which show enhanced lysis of tumor cell in vitro.
The patient has dramatically increased the number of activated, “memory-like” NK cells in circulation. Memory-like NK cells (mlNK) are activated NK cells with a unique cell surface protein phenotype and which show enhanced lysis of tumor cell in vitro.
A second program is focused on down-stream process improvements in the drug manufacturing program. Once the new strain and process is validated and functional, we will perform a manufacturing campaign drug for future clinical trials. In the future, the Company may consider a strain change to improve yield of the fermentation step further.
Once the new strain and process is validated and functional, we will perform a manufacturing campaign drug for future clinical trials. In the future, the Company may consider a strain change to improve yield of the fermentation step further. The decision for strain improvements and strain change will be made in the future as clinical development programs proceed.
Other solid cancers are of interest including nasopharyngeal cancer (“NPC”) which is a known target for NK cells and an important unmet clinical need in emerging markets such as mainland China. Renal cell carcinoma is also a known target for INKmune. We may seek to partner or sell INKmune.
As an open label trial, there may be opportunities to see patient data during 2025. Other solid cancers are of interest including nasopharyngeal cancer (“NPC”) which is a known target for NK cells and an important unmet clinical need in emerging markets such as mainland China. Renal cell carcinoma is also a known target for INKmune.
The second is to optimize the commercialization of our products either globally or regionally. The ideal partner will benefit us in both ways. We continue to look for ways to utilize our unique capabilities to optimize clinical application of cell therapies.
The second is to optimize the commercialization of our products either globally or regionally. The ideal partner will benefit us in both ways. We have leveraged our unique capabilities to optimize clinical application of cell medicines by developing CORDStrom for the treatment of RDEB.
NK cells also represent a critical effector cell for ADCC, whereby target cells bound with human antibodies, whether made by the patient’s body or administered, are selectively destroyed by the NK cells. 4 Our Innate Immune Dominant-Negative TNF (“DN-TNF”) product candidate We renamed XPro, which we license from Xencor, to INB03 when it is used for cancer related indications.
NK cells also represent a critical effector cell for ADCC, whereby target cells bound with human antibodies, whether made by the patient’s body or administered, are selectively destroyed by the NK cells. 4 Our Innate Immune Dominant-Negative TNF (“DN-TNF”) product candidate XPro1595, XPro or Pegipanermin was originally licensed from Xencor.
The Company is enrolling a global blinded randomized Phase II trial in ADi patients with Early AD in Australia (“AUS”), Canada (“CAN”), the United Kingdom (“UK”), Spain (“ES”), France (“FR”), Germany (“DE”), Poland (“PO”), the Czech Republic (“CZ”), Slovakia (“SL”) and the United States (“US”). Early AD is patients that have MCI (Mild Cognitive Impairment) or mild AD.
The Company has enrolled a global blinded randomized Phase II trial in ADi patients with Early AD in Australia, Canada, the United Kingdom, Spain, France, Germany, Poland, the Czech Republic, and Slovakia. Early AD is patients that have Mild Cognitive Impairment or mild AD.
Currently, all planned studies will be performed in North America, AUS, EU and/or the UK. Because there are no therapies similar to XPro approved in any market, we plan to take advantage of the regulatory opportunities afforded to therapies that treat markets with a high unmet need.
Because there are no therapies similar to XPro approved in any market, we plan to take advantage of the regulatory opportunities afforded to therapies that treat markets with a high unmet need.
The Immune Ventures Agreement can be terminated by Immune Ventures if, after 60 days from our receipt of notice that we have not made a payment under the Immune Ventures Agreement we still do not make this payment. On July 18, 2018, the parties amended the agreement under which the Company was required to achieve milestones pursuant to the agreement.
The Immune Ventures Agreement can be terminated by Immune Ventures if, after 60 days from our receipt of notice that we have not made a payment under the Immune Ventures Agreement we still do not make this payment.
The cost of AD to families and care givers is real and burdensome. We believe treatment of dementia patients with XPro, including Alzheimer’s disease, may provide a strategy to alter the costly dynamic of this disease in society today. Collaborate to maximize the value of our technology .
The cost of AD to families and care givers is real and burdensome. We believe treatment of dementia patients with XPro, including Alzheimer’s disease, may provide a strategy to alter the costly dynamic of this disease in society today. RDEB is a lethal and debilitating disease in children that requires life-long care-giver and medical support.
Activated glial cells cause nerve cell and oligodrocyte dysfunction that results in synaptic pruning, nerve cell death and demyelination of neurons. These pathologies contribute, in part, to neurodegenerative diseases such as AD, Parkinson’s disease, ALS, MS, Huntington’s disease, glaucoma and TBI (traumatic brain injury) may contribute to neuropsychiatric diseases such as depression, bi-polar disease, sleep disorders, autism, schizophrenia and PTSD.
These pathologies contribute, in part, to neurodegenerative diseases such as AD, Parkinson’s disease, ALS, MS, Huntington’s disease, glaucoma and TBI (traumatic brain injury) may contribute to neuropsychiatric diseases such as depression, bi-polar disease, sleep disorders, autism, schizophrenia and PTSD.
Our first interaction with the FDA occurred in July 2020 as part of the Phase II Quellor program to treat respiratory failure in patients hospitalized with COVID-19 infection. The newly manufactured XPro is being used to support the Phase II AD trial and the Expanded Access Scheme.
Our first interaction with the FDA occurred in July 2020 as part of the Phase II Quellor program to treat respiratory failure in patients hospitalized with COVID-19 infection.
The patient is now more than 12 months out from therapy with INKmune. The patient, part of the first cohort, received 1x10^8 INKmune cells on day 1,8 and 15 as an in-patient. The patient did not require any type of conditioning therapy or cytokine support. The patient tolerated the three infusions without any problems.
The patient, part of the first cohort, received 1x10^8 INKmune cells on day 1,8 and 15 as an in-patient. The patient did not require any type of conditioning therapy or cytokine support. The patient tolerated the three infusions without any problems. The patient underwent intensive monitoring over 120 days. There are 4 observations from this first patient.
Glial cell are two of four cells in the neural unit that also includes oligodendrocytes and nerve cells. Activated microglial cells are considered the resident macrophages of the brain. The primary role of microglial cells is to protect the neural unit from infection. When innate immune dysfunction causes chronic inflammation, activated microglial cells produce soluble TNF that activates astrocytes.
The primary role of microglial cells is to protect the neural unit from infection. When innate immune dysfunction causes chronic inflammation, activated microglial cells produce soluble TNF that activates astrocytes. Activated glial cells cause nerve cell and oligodrocyte dysfunction that results in synaptic pruning, nerve cell death and demyelination of neurons.
On March 11, 2021, President Biden signed the American Rescue Plan Act of 2021 into law, which eliminates the statutory Medicaid drug rebate cap, currently set at 100% of a drug’s average manufacturer price, for single source and innovator multiple source drugs, beginning January 1, 2024. Payment methodologies may also be subject to changes in healthcare legislation and regulatory initiatives.
In 2021, President Biden signed the American Rescue Plan Act of 2021 into law, which eliminated the statutory Medicaid drug rebate cap, previously set at 100% of a drug’s average manufacturer price, for single source and innovator multiple source drugs, beginning in 2024.
Patients are being enrolled who have a low burden of disease after completion of conventional therapy. The first patients were enrolled in the first quarter of 2021. In the Phase I trial, patients with detectable residual disease in bone marrow and/or peripheral blood ( The first patient was treated in the second quarter of 2021.
The first patient was enrolled in the first quarter of 2021. In the Phase I trial, we planned to treat patients with detectable residual disease in bone marrow and/or peripheral blood ( The first patient was treated in the second quarter of 2021.
We plan to use a two-step approach to improve the yield of the drug substance from the fermentation process. The company has two Phase III readiness programs in progress in preparation for the Phase III pivotal trial in patients with AD. The Company is working on the yield of the drug product using the existing E.coli-based system.
We plan to use a two-step approach to improve the yield of the drug substance from the fermentation process. The Company is working on the yield of the drug product using the existing E.coli-based system. A second program is focused on down-stream process improvements in the drug manufacturing program.
The ongoing blinded randomized global Phase II trial in patients with early ADi will enroll 201 patients in a 2:1 ratio (XPro:placebo) at 1mg/kg once a week. The trial is currently enrolling study subjects. Patients will be treated for 6 months.
AD02 is the ongoing blinded randomized global Phase II trial in patients with early AD enrolled 208 patients in a 2:1 ratio (XPro:placebo) at 1mg/kg once a week. The trial enrolled the last patient in November 2024. Patients are treated for 6 months of therapy.
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 lower reimbursement, and in additional downward pressure on the price that we receive for any approved product.
Current laws, 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 for any approved products. In the United States, it is unclear whether the ACA will be overturned or further amended.

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Item 1A. Risk Factors

Risk Factors — what could go wrong, per management

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Biggest changeAs a result, we may not complete the development and commercialization of our product candidates or develop new product candidates and have substantial doubt about our ability to continue as a going concern. ● Our ability to successfully engage with, and satisfactorily respond to, requests for information from the FDA in the future. ● We will require additional capital to fund our operations and if we fail to obtain necessary financing, we will not be able to complete the development and commercialization of our product candidates. ● We have a substantial amount of debt, and we may be unable to make required payments of interest and principal as they become due. ● We are significantly dependent on the success of our DN-TNF product platform and Natural Killer Cell Priming Platform (INKmune) and our product candidates based on these platforms. ● We need to attract and retain highly skilled personnel; we may be unable to effectively manage growth with our limited resources. ● We depend upon our senior management and key consultants and their loss or unavailability could put us at a competitive disadvantage. ● The biotechnology and immunotherapy industries are characterized by rapid technological developments and a high degree of competition.
Biggest changeWe are not currently profitable, and we may never achieve or sustain profitability. ● We will require additional capital to fund our operations and if we fail to obtain necessary financing, we will not be able to complete the development and commercialization of our product candidates. ● We are significantly dependent on the success of our DN-TNF product platform and Natural Killer Cell Priming Platform (INKmune), CORDStrom, and our product candidates based on these platforms. ● We need to attract and retain highly skilled personnel; we may be unable to effectively manage growth with our limited resources. ● We depend upon our senior management and key consultants and their loss or unavailability could put us at a competitive disadvantage. ● The biotechnology and immunotherapy industries are characterized by rapid technological developments and a high degree of competition.
The development and commercialization of new drug products is highly competitive. We expect that we will face significant competition from major pharmaceutical companies, specialty pharmaceutical companies and biotechnology companies worldwide with respect to INKmune, our DN-TNF product platform, and any other of our product candidates that we may seek to develop or commercialize in the future.
The development and commercialization of new drug products is highly competitive. We expect that we will face significant competition from major pharmaceutical companies, specialty pharmaceutical companies and biotechnology companies worldwide with respect to our DN-TNF product platform, INKmune and any other of our product candidates that we may seek to develop or commercialize in the future.
We may experience numerous unforeseen events during, or as a result of, clinical trials that could delay or prevent marketing approval of any of our product candidates, including: ● clinical trials of our product candidate may produce unfavorable or inconclusive results; ● we may decide, or regulators may require us, to conduct additional clinical trials or abandon product development programs; ● the number of patients required for clinical trials of our product candidate may be larger than we anticipate, patient enrollment in these clinical trials may be slower than we anticipate, or participants may drop out of these clinical trials at a higher rate than we anticipate; ● data safety monitoring committees may recommend suspension, termination or a clinical hold for various reasons, including concerns about patient safety; ● regulators or institutional review boards, or IRBs, may suspend or terminate the trial or impose a clinical hold for various reasons, including noncompliance with regulatory requirements or concerns about patient safety; ● patients with serious, life-threatening diseases included in our clinical trials may die or suffer other adverse medical events for reasons that may not be related to our product candidate; ● participating patients may be subject to unacceptable health risks; ● patients may not complete clinical trials due to safety issues, side effects, or other reasons; ● changes in regulatory requirements and guidance may occur, which require us to amend clinical trial protocols to reflect these changes; ● our third-party contractors, including those manufacturing our product candidate or components or ingredients thereof or conducting clinical trials on our behalf, may fail to comply with regulatory requirements or meet their contractual obligations to us in a timely manner or at all; ● regulators or IRBs may not authorize us or our investigators to commence a clinical trial or conduct a clinical trial at a prospective trial site; ● we may experience delays in reaching or fail to reach agreement on acceptable clinical trial contracts or clinical trial protocols with prospective trial sites; ● patients who enroll in a clinical trial may misrepresent their eligibility to do so or may otherwise not comply with the clinical trial protocol, resulting in the need to drop the patients from the clinical trial, increase the needed enrollment size for the clinical trial or extend the clinical trial’s duration; ● we may have to suspend or terminate clinical trials of our product candidate for various reasons, including a finding that the participants are being exposed to unacceptable health risks, undesirable side effects or other unexpected characteristics of a product candidate; 43 ● the FDA or comparable non-U.S. regulatory authorities may disagree with our clinical trial design or our interpretation of data from preclinical studies and clinical trials; ● the FDA or comparable non-U.S. regulatory authorities may fail to approve or subsequently find fault with the manufacturing processes or facilities of third-party manufacturers with which we enter into agreements for clinical and commercial supplies; ● the supply or quality of raw materials or manufactured product candidate or other materials necessary to conduct clinical trials of our product candidate may be insufficient, inadequate, delayed, or not available at an acceptable cost, or we may experience interruptions in supply; and ● the approval policies or regulations of the FDA or comparable non-U.S. regulatory authorities may significantly change in a manner rendering our clinical data insufficient to obtain marketing approval.
We may experience numerous unforeseen events during, or as a result of, clinical trials that could delay or prevent marketing approval of any of our product candidates, including: ● clinical trials of our product candidate may produce unfavorable or inconclusive results; ● we may decide, or regulators may require us, to conduct additional clinical trials or abandon product development programs; ● the number of patients required for clinical trials of our product candidate may be larger than we anticipate, patient enrollment in these clinical trials may be slower than we anticipate, or participants may drop out of these clinical trials at a higher rate than we anticipate; ● data safety monitoring committees may recommend suspension, termination or a clinical hold for various reasons, including concerns about patient safety; ● regulators or institutional review boards, or IRBs, may suspend or terminate the trial or impose a clinical hold for various reasons, including noncompliance with regulatory requirements or concerns about patient safety; ● patients with serious, life-threatening diseases included in our clinical trials may die or suffer other adverse medical events for reasons that may not be related to our product candidate; ● participating patients may be subject to unacceptable health risks; ● patients may not complete clinical trials due to safety issues, side effects, or other reasons; ● changes in regulatory requirements and guidance may occur, which require us to amend clinical trial protocols to reflect these changes; ● our third-party contractors, including those manufacturing our product candidate or components or ingredients thereof or conducting clinical trials on our behalf, may fail to comply with regulatory requirements or meet their contractual obligations to us in a timely manner or at all; ● regulators or IRBs may not authorize us or our investigators to commence a clinical trial or conduct a clinical trial at a prospective trial site; ● we may experience delays in reaching or fail to reach agreement on acceptable clinical trial contracts or clinical trial protocols with prospective trial sites; ● patients who enroll in a clinical trial may misrepresent their eligibility to do so or may otherwise not comply with the clinical trial protocol, resulting in the need to drop the patients from the clinical trial, increase the needed enrollment size for the clinical trial or extend the clinical trial’s duration; ● we may have to suspend or terminate clinical trials of our product candidate for various reasons, including a finding that the participants are being exposed to unacceptable health risks, undesirable side effects or other unexpected characteristics of a product candidate; 35 ● the FDA or comparable non-U.S. regulatory authorities may disagree with our clinical trial design or our interpretation of data from preclinical studies and clinical trials; ● the FDA or comparable non-U.S. regulatory authorities may fail to approve or subsequently find fault with the manufacturing processes or facilities of third-party manufacturers with which we enter into agreements for clinical and commercial supplies; ● the supply or quality of raw materials or manufactured product candidate or other materials necessary to conduct clinical trials of our product candidate may be insufficient, inadequate, delayed, or not available at an acceptable cost, or we may experience interruptions in supply; and ● the approval policies or regulations of the FDA or comparable non-U.S. regulatory authorities may significantly change in a manner rendering our clinical data insufficient to obtain marketing approval.
The market price of our common stock is likely to be highly volatile and could fluctuate widely in price in response to various factors, many of which are beyond our control, including the following: ● changes in our industry; ● competitive pricing pressures; 56 ● our ability to obtain working capital financing; ● additions or departures of key personnel; ● limited “public float” in the hands of a small number of persons whose sales or lack of sales could result in positive or negative pricing pressure on the market price for our common stock; ● sales of our common stock; ● our ability to execute our business plan; ● operating results that fall below expectations; ● loss of any strategic relationship; ● regulatory developments; ● economic and other external factors; ● period-to-period fluctuations in our financial results; and ● inability to develop or acquire new or needed technology or products.
The market price of our common stock is likely to be highly volatile and could fluctuate widely in price in response to various factors, many of which are beyond our control, including the following: ● changes in our industry; ● competitive pricing pressures; ● our ability to obtain working capital financing; ● additions or departures of key personnel; ● limited “public float” in the hands of a small number of persons whose sales or lack of sales could result in positive or negative pricing pressure on the market price for our common stock; ● sales of our common stock; ● our ability to execute our business plan; ● operating results that fall below expectations; ● loss of any strategic relationship; ● regulatory developments; ● economic and other external factors; ● period-to-period fluctuations in our financial results; and ● inability to develop or acquire new or needed technology or products.
The degree of market acceptance of INmune or any other product candidate we develop, if approved for commercial sale, will depend on a number of factors, including: ● the efficacy and safety of the product; ● the potential advantages of the product compared to alternative treatments; ● the prevalence and severity of any side effects; ● the clinical indications for which the product is approved; ● whether the product is designated under physician treatment guidelines as a first-line therapy or as a second- or third-line therapy; ● limitations or warnings, including distribution or use restrictions, contained in the product’s approved labeling; ● our ability to offer the product for sale at competitive prices; ● our ability to establish and maintain pricing sufficient to realize a meaningful return on our investment; ● the product’s convenience and ease of administration compared to alternative treatments; 46 ● the willingness of the target patient population to try, and of physicians to prescribe, the product; ● the strength of sales, marketing and distribution support; ● the approval of other new products for the same indications; ● changes in the standard of care for the targeted indications for the product; ● the timing of market introduction of our approved products as well as competitive products and other therapies; ● availability and amount of reimbursement from government payors, managed care plans and other third-party payors; ● adverse publicity about the product or favorable publicity about competitive products; and ● potential product liability claims.
The degree of market acceptance of INmune or any other product candidate we develop, if approved for commercial sale, will depend on a number of factors, including: ● the efficacy and safety of the product; ● the potential advantages of the product compared to alternative treatments; ● the prevalence and severity of any side effects; ● the clinical indications for which the product is approved; ● whether the product is designated under physician treatment guidelines as a first-line therapy or as a second- or third-line therapy; ● limitations or warnings, including distribution or use restrictions, contained in the product’s approved labeling; ● our ability to offer the product for sale at competitive prices; ● our ability to establish and maintain pricing sufficient to realize a meaningful return on our investment; ● the product’s convenience and ease of administration compared to alternative treatments; 38 ● the willingness of the target patient population to try, and of physicians to prescribe, the product; ● the strength of sales, marketing and distribution support; ● the approval of other new products for the same indications; ● changes in the standard of care for the targeted indications for the product; ● the timing of market introduction of our approved products as well as competitive products and other therapies; ● availability and amount of reimbursement from government payors, managed care plans and other third-party payors; ● adverse publicity about the product or favorable publicity about competitive products; and ● potential product liability claims.
Even if INKmune, our DN-TNF product platform (INB03 or XPro), or any other product candidate we develop is approved by the appropriate regulatory authorities for marketing and sale, it may nonetheless fail to gain sufficient market acceptance by physicians, patients, third-party payors and others in the medical community.
Even if CORDStrom, INKmune, our DN-TNF product platform (INB03 or XPro), or any other product candidate we develop is approved by the appropriate regulatory authorities for marketing and sale, it may nonetheless fail to gain sufficient market acceptance by physicians, patients, third-party payors and others in the medical community.
In addition, later discovery of previously unknown problems with our products, manufacturing processes, or failure to comply with regulatory requirements, may lead to various adverse results, including: ● restrictions on such products, manufacturers or manufacturing processes; ● restrictions on the labeling or marketing of a product; ● restrictions on product distribution or use; 48 ● requirements to conduct post-marketing clinical trials; ● requirements to institute a risk evaluation mitigation strategy, or REMS, to monitor safety of the product post-approval; ● warning letters issued by the FDA or other regulatory authorities; ● withdrawal of the products from the market; ● refusal to approve pending applications or supplements to approved applications that we submit; ● recall of products, fines, restitution or disgorgement of profits or revenue; ● suspension, revocation or withdrawal of marketing approvals; ● refusal to permit the import or export of our products; and ● injunctions or the imposition of civil or criminal penalties.
In addition, later discovery of previously unknown problems with our products, manufacturing processes, or failure to comply with regulatory requirements, may lead to various adverse results, including: ● restrictions on such products, manufacturers or manufacturing processes; ● restrictions on the labeling or marketing of a product; ● restrictions on product distribution or use; 40 ● requirements to conduct post-marketing clinical trials; ● requirements to institute a risk evaluation mitigation strategy, or REMS, to monitor safety of the product post-approval; ● warning letters issued by the FDA or other regulatory authorities; ● withdrawal of the products from the market; ● refusal to approve pending applications or supplements to approved applications that we submit; ● recall of products, fines, restitution or disgorgement of profits or revenue; ● suspension, revocation or withdrawal of marketing approvals; ● refusal to permit the import or export of our products; and ● injunctions or the imposition of civil or criminal penalties.
Our licensors may also seek to terminate our license. We are a party to a number of licenses that give us rights to third-party intellectual property that is necessary or useful to our business. To this end, we are dependent on our licenses with Xencor, Inc., Immune Ventures, LLC and the University of Pittsburgh.
Our licensors may also seek to terminate our license. We are a party to a number of licenses that give us rights to third-party intellectual property that is necessary or useful to our business. To this end, we are dependent on our licenses with Xencor, Inc., Immune Ventures, LLC, the University of Pittsburgh and GOSH.
We are engaged in a rapidly changing field. Other products and therapies that will compete directly with the product that we are seeking to develop and market currently exist or are being developed. Competition from fully integrated pharmaceutical companies and more established biotechnology companies is intense and is expected to increase.
We are engaged in a rapidly changing field. Other products and therapies that will compete directly with the products that we are seeking to develop and market currently exist or are being developed. Competition from fully integrated pharmaceutical companies and more established biotechnology companies is intense and is expected to increase.
Patient enrollment is a significant factor in the timing of clinical trials, and is affected by many factors, including: ● the size and nature of the patient population; ● the severity of the disease under investigation; ● the proximity of patients to clinical sites; ● the eligibility criteria for the trial; ● the design of the clinical trial; ● efforts to facilitate timely enrollment; ● competing clinical trials; and ● clinicians’ and patients’ perceptions as to the potential advantages and risks of the drug being studied in relation to other available therapies, including any new drugs that may be approved for the indications we are investigating. 44 Our inability to enroll a sufficient number of patients for our clinical trials could result in significant delays or may require us to abandon one or more clinical trials altogether.
Patient enrollment is a significant factor in the timing of clinical trials, and is affected by many factors, including: ● the size and nature of the patient population; ● the severity of the disease under investigation; ● the proximity of patients to clinical sites; ● the eligibility criteria for the trial; ● the design of the clinical trial; ● efforts to facilitate timely enrollment; ● competing clinical trials; and ● clinicians’ and patients’ perceptions as to the potential advantages and risks of the drug being studied in relation to other available therapies, including any new drugs that may be approved for the indications we are investigating. 36 Our inability to enroll a sufficient number of patients for our clinical trials could result in significant delays or may require us to abandon one or more clinical trials altogether.
In addition, the securities markets have from time-to-time experienced significant price and volume fluctuations that are unrelated to the operating performance of particular companies. These market fluctuations may also materially and adversely affect the market price of our Common Stock. You may have difficulty trading and obtaining quotations for our common stock.
In addition, the securities markets have from time-to-time experienced significant price and volume fluctuations that are unrelated to the operating performance of particular companies. These market fluctuations may also materially and adversely affect the market price of our Common Stock. 52 You may have difficulty trading and obtaining quotations for our common stock.
We may not be able to initiate or continue clinical trials for INKmune our DN-TNF product platform or any other product candidate if we are unable to locate and enroll a sufficient number of eligible patients to participate in clinical trials.
We may not be able to initiate or continue clinical trials for CORDStrom, INKmune our DN-TNF product platform or any other product candidate if we are unable to locate and enroll a sufficient number of eligible patients to participate in clinical trials.
If we obtain regulatory approvals, INKmune and/or the DN-TNF product platform, and the manufacturing facilities used for its production will be subject to continual review, including periodic inspections, by the FDA and other United States and foreign regulatory authorities.
If we obtain regulatory approvals, CORDStrom, INKmune and/or the DN-TNF product platform, and the manufacturing facilities used for its production will be subject to continual review, including periodic inspections, by the FDA and other United States and foreign regulatory authorities.
We may be unable to compete with more substantial enterprises. ● We can provide no assurance that our clinical product candidates will obtain regulatory approval or that the results of clinical studies will be favorable. ● Drug discovery and development is a complex, time-consuming and expensive process with a high rate of failure. ● We may face legal claims; legal disputes are expensive, and we may not be able to afford the costs. ● We can provide no assurance of the successful and timely development of new products. ● We must comply with significant government regulations. 33 ● We rely upon patents to protect our technology.
We may be unable to compete with more substantial enterprises. ● We can provide no assurance that our clinical product candidates will obtain regulatory approval or that the results of clinical studies will be favorable. ● Drug discovery and development is a complex, time-consuming and expensive process with a high rate of failure. ● We may face legal claims; legal disputes are expensive, and we may not be able to afford the costs. ● We can provide no assurance of the successful and timely development of new products. ● We must comply with significant government regulations. 29 ● We rely upon patents to protect our technology.
The discovery of previously unknown problems with INKmune, the DN-TNF product platform or manufacturing facilities used to manufacture INKmune, or the DN-TNF product platform may result in restrictions or sanctions on our products or manufacturing facilities, including withdrawal of our products from the market.
The discovery of previously unknown problems with CORDStrom, INKmune, the DN-TNF product platform or manufacturing facilities used to manufacture CORDStrom, INKmune, or the DN-TNF product platform may result in restrictions or sanctions on our products or manufacturing facilities, including withdrawal of our products from the market.
If we are unable to obtain or maintain sufficient insurance coverage at an acceptable cost or to otherwise protect against potential product liability claims, it could prevent or inhibit the development and commercial production and sale of our product candidate, which could adversely affect our business, financial condition, results of operations and prospects. 50 We will need to increase the size and capabilities of our organization, and we may experience difficulties in managing this growth.
If we are unable to obtain or maintain sufficient insurance coverage at an acceptable cost or to otherwise protect against potential product liability claims, it could prevent or inhibit the development and commercial production and sale of our product candidate, which could adversely affect our business, financial condition, results of operations and prospects. 42 We will need to increase the size and capabilities of our organization, and we may experience difficulties in managing this growth.
Our competitors may succeed in developing, acquiring or licensing technologies and drug products that are more effective, have fewer or more tolerable side effects or are less costly than any product candidates that we are currently developing or that we may develop, which could render our product candidates obsolete and noncompetitive. 49 We rely on key personnel and, if we are unable to retain or motivate key personnel or hire qualified personnel, we may not be able to grow effectively.
Our competitors may succeed in developing, acquiring or licensing technologies and drug products that are more effective, have fewer or more tolerable side effects or are less costly than any product candidates that we are currently developing or that we may develop, which could render our product candidates obsolete and noncompetitive. 41 We rely on key personnel and, if we are unable to retain or motivate key personnel or hire qualified personnel, we may not be able to grow effectively.
This may cause our reputation in the marketplace to suffer or subject us to lawsuits, including class action suits. 47 If our product candidates receive marketing approval and we, or others, later discover that the drug is less effective than previously believed or causes undesirable side effects that were not previously identified, our ability to market the drugs could be compromised.
This may cause our reputation in the marketplace to suffer or subject us to lawsuits, including class action suits. 39 If our product candidates receive marketing approval and we, or others, later discover that the drug is less effective than previously believed or causes undesirable side effects that were not previously identified, our ability to market the drugs could be compromised.
The opinion of our independent registered public accounts on our audited financial statements for the year ended December 31, 2023, contains an explanatory paragraph regarding substantial doubt about our ability to continue as a going concern. There is no assurance that we will be successful in raising the additional funds needed to fund our business plan.
The opinion of our independent registered public accounts on our audited financial statements for the year ended December 31, 2024, contains an explanatory paragraph regarding substantial doubt about our ability to continue as a going concern. There is no assurance that we will be successful in raising the additional funds needed to fund our business plan.
If investigators or institutions breach their obligations with respect to the clinical trials of our product candidate, or if the data proves to be inadequate, then our ability to design and conduct any future clinical trials may be adversely affected. 51 Our reliance on these third parties for research and development activities will reduce our control over these activities but will not relieve us of our responsibilities.
If investigators or institutions breach their obligations with respect to the clinical trials of our product candidate, or if the data proves to be inadequate, then our ability to design and conduct any future clinical trials may be adversely affected. 44 Our reliance on these third parties for research and development activities will reduce our control over these activities but will not relieve us of our responsibilities.
We have not previously submitted an NDA to the FDA or similar drug approval filings to comparable non-U.S. regulatory authorities for any product candidate. 42 Any inability to successfully complete preclinical and clinical development could result in additional costs to us and impair our ability to generate revenues from product sales, regulatory and commercialization milestones and royalties.
We have not previously submitted an NDA to the FDA or similar drug approval filings to comparable non-U.S. regulatory authorities for any product candidate. 34 Any inability to successfully complete preclinical and clinical development could result in additional costs to us and impair our ability to generate revenues from product sales, regulatory and commercialization milestones and royalties.
This preference for U.S. industry may limit our ability to contract with non-U.S. product manufacturers for products covered by such intellectual property. 37 We license our patents from others. If such owners do not properly maintain or enforce the intellectual property underlying such licenses, our competitive position and business prospects could be harmed.
This preference for U.S. industry may limit our ability to contract with non-U.S. product manufacturers for products covered by such intellectual property. 50 We license our patents from others. If such owners do not properly maintain or enforce the intellectual property underlying such licenses, our competitive position and business prospects could be harmed.
If sales by employees, executive officers, or directors cause a substantial number of our common shares to become available for purchase in the public market, the price of our common shares could fall or may not increase. Also, sales by such personnel could be viewed negatively by holders and potential purchasers of our common shares. 57
If sales by employees, executive officers, or directors cause a substantial number of our common shares to become available for purchase in the public market, the price of our common shares could fall or may not increase. Also, sales by such personnel could be viewed negatively by holders and potential purchasers of our common shares. 53
Even if coverage is provided, the approved reimbursement amount may not be high enough to allow us to establish and maintain pricing sufficient to realize a meaningful return on our investment. 38 There is significant uncertainty related to third-party payor coverage and reimbursement of newly approved drugs.
Even if coverage is provided, the approved reimbursement amount may not be high enough to allow us to establish and maintain pricing sufficient to realize a meaningful return on our investment. 31 There is significant uncertainty related to third-party payor coverage and reimbursement of newly approved drugs.
Such actions could have a significant impact on our business and results of operations, including the imposition of significant fines or other sanctions. 54 A cybersecurity incident and other technological disruptions could negatively affect our business and our relationships with customers. We use technology in substantially all aspects of our business operations.
Such actions could have a significant impact on our business and results of operations, including the imposition of significant fines or other sanctions. 47 A cybersecurity incident and other technological disruptions could negatively affect our business and our relationships with customers. We use technology in substantially all aspects of our business operations.
Receiving priority review from the FDA does not guarantee approval within an accelerated timeline or thereafter. 40 We believe we may in some instances be able to secure approval from the FDA or comparable non-U.S. regulatory authorities to use accelerated development pathways.
Receiving priority review from the FDA does not guarantee approval within an accelerated timeline or thereafter. 32 We believe we may in some instances be able to secure approval from the FDA or comparable non-U.S. regulatory authorities to use accelerated development pathways.
Thus, even if we or our licensors are able to obtain patents, the patents may be substantially narrower than anticipated. 36 Our success depends on patent applications that are licensed exclusively to us and other patents to which we may obtain assignment or licenses.
Thus, even if we or our licensors are able to obtain patents, the patents may be substantially narrower than anticipated. 49 Our success depends on patent applications that are licensed exclusively to us and other patents to which we may obtain assignment or licenses.
The Medicare Drug Price Negotiation Program is currently subject to legal challenges and therefore, the outcome of the 340B Program remains uncertain. 53 Payors may promote generic drugs and biosimilars more aggressively to generate savings and attempt to stimulate additional price competition.
The Medicare Drug Price Negotiation Program is currently subject to legal challenges and therefore, the outcome of the 340B Program remains uncertain. 46 Payors may promote generic drugs and biosimilars more aggressively to generate savings and attempt to stimulate additional price competition.
Even if we obtain regulatory approvals for INKmune and/or any product from our DN-TNF platform (INB03, XPro) those approvals and ongoing regulation of our products may limit how we manufacture and market our products, which could prevent us from realizing the full benefit of our efforts.
Even if we obtain regulatory approvals for CORDStrom, INKmune and/or any product from our DN-TNF platform those approvals and ongoing regulation of our products may limit how we manufacture and market our products, which could prevent us from realizing the full benefit of our efforts.
The rights under the plan will expire on December 30, 2024, subject to a possible earlier expiration to the extent provided in the stockholder rights plan, unless extended.
The rights under the plan will expire on December 30, 2025, subject to a possible earlier expiration to the extent provided in the stockholder rights plan, unless extended.
It may be time consuming, difficult and costly for us to develop and implement the internal controls and reporting procedures required by the Sarbanes-Oxley Act. We may need to hire additional financial reporting, internal controls and other finance personnel in order to develop and implement appropriate internal controls and reporting procedures.
It may be time consuming, difficult and costly for us to develop and implement the internal controls and reporting procedures required by the Sarbanes-Oxley Act. We may need to hire additional financial reporting, internal controls and other finance personnel in order to develop and implement appropriate internal controls and reporting procedures. Our stock price may be volatile.
If we lose any of our right to use third-party intellectual property, it could adversely affect our ability to commercialize our technologies, products or services, as well as harm our competitive business position and our business prospects. We are dependent on our licensing agreement with Xencor, and the termination of this agreement could have an adverse effect on our business.
If we lose any of our right to use third-party intellectual property, it could adversely affect our ability to commercialize our technologies, products or services, as well as harm our competitive business position and our business prospects. We are dependent on our licensing agreement with Xencor, and the termination of this agreement would harm our business.
Periods of non-patent exclusivity for new versions of existing drugs such as our current product candidates can extend up to three and one-half years. See “Business — Government Regulation.” These competitive factors could require us to conduct substantial new research and development activities to establish new product targets, which would be costly and time-consuming.
Periods of non-patent exclusivity for new versions of existing drugs such as our current product candidates can extend up to three and one-half years. See the section entitled “Government Regulation.” These competitive factors could require us to conduct substantial new research and development activities to establish new product targets, which would be costly and time-consuming.
Such conflict could limit the scope of the patents, if any, that we may be able to obtain or result in the denial of our patent applications.
Some of these technologies, applications or patents may conflict with our technologies or patent applications. Such conflict could limit the scope of the patents, if any, that we may be able to obtain or result in the denial of our patent applications.
We may be unable to build a successful brand identity for a new trademark in a timely manner or at all, which would limit our ability to commercialize our product candidates.
We may be unable to build a successful brand identity for a new trademark in a timely manner or at all, which would limit our ability to commercialize our product candidates. 37 We may fail to comply with regulatory requirements .
RISKS RELATED TO OUR BUSINESS There is doubt about our ability to continue as a going concern. As of December 31, 2023, the Company had an accumulated deficit of $121,022,000.
RISKS RELATED TO OUR BUSINESS There is doubt about our ability to continue as a going concern. As of December 31, 2024, the Company had an accumulated deficit of $163,104,000.
Specifically, the rights issued under the stockholder rights plan could cause significant dilution to a person or group that attempts to acquire us on terms not approved in advance by our board of directors.
We have a stockholder rights plan that may have the effect of discouraging unsolicited takeover proposals. Specifically, the rights issued under the stockholder rights plan could cause significant dilution to a person or group that attempts to acquire us on terms not approved in advance by our board of directors.
To execute our business plan, we will need to rapidly add other management, accounting, regulatory, manufacturing and scientific staff. We currently have 11 full-time employees, 6 part-time employees and retain the services of additional personnel on an independent contractor basis.
To execute our business plan, we will need to rapidly add other management, accounting, regulatory, manufacturing and scientific staff. We currently have 13 full-time employees in the United States, 9 full-time employees in the United Kingdom and retain the services of additional personnel on an independent contractor basis.
Our reliance on third parties to conduct clinical trials could, depending on the actions of such third parties, jeopardize the validity of the clinical data generated and adversely affect our ability to obtain marketing approval from the FDA or other applicable regulatory authorities.
We plan to rely on contract research organizations to conduct clinical trials relating to our product candidates. Our reliance on third parties to conduct clinical trials could, depending on the actions of such third parties, jeopardize the validity of the clinical data generated and adversely affect our ability to obtain marketing approval from the FDA or other applicable regulatory authorities.
Clinical drug development involves a lengthy and expensive process with an uncertain outcome. We may incur additional costs or experience delays in completing, or ultimately be unable to complete the development and commercialization of our product candidate. Our product candidates are either in early clinical development or have not entered into clinical trials and are in development stage.
Clinical drug development involves a lengthy and expensive process with an uncertain outcome. We may incur additional costs or experience delays in completing, or ultimately be unable to complete the development and commercialization of our product candidate. Our product candidates are in early clinical development. Therefore, the risk of failure of our product candidates is high.
We face intense competition in the markets targeted by our lead product candidates. Many of our competitors have substantially greater resources than we do, and we expect that all of our product candidates under development will face intense competition from existing or future drugs.
Many of our competitors have substantially greater resources than we do, and we expect that all of our product candidates under development will face intense competition from existing or future drugs. We expect that our product candidates under development, if approved, will face intense competition from existing and future drugs marketed by large companies.
If we breach this Agreement, Xencor may be able to terminate it, which could be negatively impact our business. Our officers and Directors own the company that we license our INKmune patent from. On October 29, 2015, we entered into an exclusive license agreement with Immune Ventures, LLC (Immune Ventures). The license agreement relates to our natural killer program, INKmune.
If we breach this Agreement, Xencor may be able to terminate it, which would harm our business. Our officers and Chairman of the Board own the company that we license our INKmune patent from. On October 29, 2015, we entered into an exclusive license agreement with Immune Ventures, LLC (Immune Ventures).
We have received, and are currently seeking, patent protection for numerous compounds and methods of treating diseases. However, the patent process is subject to numerous risks and uncertainties, and there can be no assurance that we will be successful in protecting our products by obtaining and defending patents.
However, the patent process is subject to numerous risks and uncertainties, and there can be no assurance that we will be successful in protecting our products by obtaining and defending patents.
In September 2011, the Leahy-Smith America Invents Act, or the American Invents Act, or AIA, was signed into law. The AIA includes a number of significant changes to U.S. patent law, including provisions that affect the way patent applications will be prosecuted and may also affect patent litigation.
The Leahy-Smith Act included a number of significant changes to U.S. patent law, including provisions that affect the way patent applications will be prosecuted and that may also affect patent litigation.
These competitors may successfully market products that compete with our products, successfully identify drug candidates or develop products earlier than we do, or develop products that are more effective, have fewer side effects or cost less than our products, if any. 35 Additionally, if a competitor receives FDA approval before we do for a drug that is similar to one of our product candidates, FDA approval for our product candidate may be precluded or delayed due to periods of non-patent exclusivity and/or the listing with the FDA by the competitor of patents covering its newly-approved drug product.
Additionally, if a competitor receives FDA approval before we do for a drug that is similar to one of our product candidates, FDA approval for our product candidate may be precluded or delayed due to periods of non-patent exclusivity and/or the listing with the FDA by the competitor of patents covering its newly-approved drug product.
Any of these events could have a material adverse effect on our business, prospects, operating results and financial condition and could adversely affect the price of our common shares.
Any of these events could have a material adverse effect on our business, prospects, operating results and financial condition and could adversely affect the price of our common shares. Risks Related to our Intellectual Property We depend on obtaining certain patents and protecting our proprietary rights.
If we are not able to raise sufficient capital in the near future, our continued operations will be in jeopardy and we may be forced to cease operations and sell or otherwise transfer all or substantially all of our remaining assets. 34 To fund our operations and service our debt, we will be required to generate a significant amount of cash.
If we are not able to raise sufficient capital in the near future, our continued operations will be in jeopardy and we may be forced to cease operations and sell or otherwise transfer all or substantially all of our remaining assets. We face intense competition in the markets targeted by our lead product candidates.
There can be no assurance, however, that these agreements will provide meaningful protection for our trade secrets, know-how or other proprietary information in the event of any unauthorized use or disclosure.
There can be no assurance, however, that these agreements will provide meaningful protection for our trade secrets, know-how or other proprietary information in the event of any unauthorized use or disclosure. Further, our business may be adversely affected by competitors who independently develop competing technologies, especially if we obtain no, or only narrow, patent protection.
The goal of ACA is to reduce the cost of healthcare, broaden access to health insurance, constrain healthcare spending, enhance remedies against fraud and abuse, add transparency requirements for the healthcare and health insurance industries, impose taxes and fees on the health industry, impose additional health policy reforms, and substantially change the way healthcare is financed by both governmental and private insurers.
The PPACA was intended to broaden access to health insurance, reduce or constrain the growth of healthcare spending, enhance remedies against healthcare fraud and abuse, add new transparency requirements for healthcare and health insurance industries, impose new taxes and fees on the health industry and impose additional health policy reforms.
Before obtaining marketing approval from regulatory authorities for the sale of any product candidate, we must complete preclinical development and then conduct extensive clinical trials to demonstrate the safety and efficacy of our product candidate in humans. Clinical testing is expensive, difficult to design and implement, can take many years to complete and is uncertain as to outcome.
It is impossible to predict when or if our product candidates will prove effective or safe in humans or will receive regulatory approval. Before obtaining marketing approval from regulatory authorities for the sale of any product candidate, we must complete preclinical development and then conduct extensive clinical trials to demonstrate the safety and efficacy of our product candidate in humans.
Other companies may succeed in developing products earlier than us, obtaining FDA approval for products more rapidly, or developing products that are more effective than our product candidates. Research and development by others may render our technology or product candidates obsolete or noncompetitive or result in treatments or cures superior to any therapy we develop.
Research and development by others may render our technology or product candidates obsolete or noncompetitive or result in treatments or cures superior to any therapy we develop. We face competition from companies that internally develop competing technology or acquire competing technology from universities and other research institutions.
A number of pharmaceutical, biopharmaceutical and biotechnology companies and research and academic institutions have developed technologies, filed patent applications or received patents on various technologies that may be related to or affect our business. Some of these technologies, applications or patents may conflict with our technologies or patent applications.
If we do not obtain such licenses, we could encounter delays in the introduction of products or could find that the development, manufacture or sale of products requiring such licenses could be prohibited. 48 A number of pharmaceutical, biopharmaceutical and biotechnology companies and research and academic institutions have developed technologies, filed patent applications or received patents on various technologies that may be related to or affect our business.
Additionally, because our target patient populations are small, we will be required to capture a significant market share to achieve and maintain profitability. We may fail to comply with regulatory requirements . Our success will be dependent upon our ability, and our collaborative partners’ abilities, to maintain compliance with regulatory requirements, including cGMP, and safety reporting obligations.
Our success will be dependent upon our ability, and our collaborative partners’ abilities, to maintain compliance with regulatory requirements, including cGMP, and safety reporting obligations.
These activities would adversely affect our ability to commercialize products and achieve revenue and profits. Competition and technological change may make our product candidates and technologies less attractive or obsolete. We compete with established pharmaceutical and biotechnology companies that are pursuing other forms of treatment for the same indications we are pursuing and that have greater financial and other resources.
These activities would adversely affect our ability to commercialize products and achieve revenue and profits. 30 Competition and technological change may make our product candidates and technologies less attractive or obsolete.
Some foreign countries lack rules and methods for defending intellectual property rights and do not protect proprietary rights to the same extent as the United States. Many companies have had difficulty protecting their proprietary rights in these foreign countries. We may not be able to prevent misappropriation of our proprietary rights.
If we do not adequately protect our intellectual property, competitors may be able to use our technologies to produce and market drugs in direct competition with us and erode our competitive advantage. Some foreign countries lack rules and methods for defending intellectual property rights and do not protect proprietary rights to the same extent as the United States.
Similarly, in our clinical trials we may fail to detect toxicity of, or intolerability caused by our product candidates, or mistakenly believe that our product candidates are toxic or not well tolerated when that is not in fact the case. 41 The outcome of preclinical studies and early clinical trials may not be predictive of the success of later clinical trials, and interim results of a clinical trial do not necessarily predict final results.
Similarly, in our clinical trials we may fail to detect toxicity of, or intolerability caused by our product candidates, or mistakenly believe that our product candidates are toxic or not well tolerated when that is not in fact the case. 33 Success in early development does not mean that later development will be successful because, for example, drug candidates in later-stage clinical trials may fail to demonstrate sufficient safety and efficacy despite having progressed through initial clinical trials.
Further, recent U.S. Supreme Court rulings have either narrowed the scope of patent protection available in certain circumstances or weakened the rights of patent owners in certain situations. In addition to increasing uncertainty with regard to our ability to obtain patents in the future, this combination of events has created uncertainty with respect to the value of patents, once obtained.
In addition to increasing uncertainty with regard to our ability to obtain patents in the future, this combination of events has created uncertainty with respect to the value of patents, once obtained. Depending on decisions by the U.S.
A failure of one or more clinical trials can occur at any stage of testing.
Clinical testing is expensive, difficult to design and implement, can take many years to complete and is uncertain as to outcome. A failure of one or more clinical trials can occur at any stage of testing.
As is the case with other pharmaceutical companies, our success is heavily dependent on intellectual property, particularly on obtaining and enforcing patents. Obtaining and enforcing patents in the pharmaceutical industry involves both technological and legal complexity, and therefore, is costly, time-consuming and inherently uncertain. In addition, the United States has recently enacted and is currently implementing wide-ranging patent reform legislation.
As is the case with other biopharmaceutical companies, our success is heavily dependent on intellectual property, particularly patents. Obtaining and enforcing patents in the biopharmaceutical industry involves both technological and legal complexity and is costly, time-consuming and inherently uncertain. For example, on September 16, 2011, the Leahy-Smith America Invents Act, or the Leahy-Smith Act, was signed into law.
Our success will depend, in part, on our ability to obtain patents and maintain adequate protection of our technologies and products. If we do not adequately protect our intellectual property, competitors may be able to use our technologies to produce and market drugs in direct competition with us and erode our competitive advantage.
If we fail to protect our intellectual property rights, our ability to pursue the development of our technologies and products would be negatively affected. Our success will depend, in part, on our ability to obtain patents and maintain adequate protection of our technologies and products.
Further, our business may be adversely affected by competitors who independently develop competing technologies, especially if we obtain no, or only narrow, patent protection. 39 We are subject to various government regulations. The manufacture and sale of human therapeutic products in the U.S. and foreign jurisdictions are governed by a variety of statutes and regulations.
Adverse pricing limitations may hinder our ability to recoup our investment in one or more product candidates, even if our product candidates obtain marketing approval. We are subject to various government regulations. The manufacture and sale of human therapeutic products in the U.S. and foreign jurisdictions are governed by a variety of statutes and regulations.
Immune Ventures is owned by our RJ Tesi, our CEO and Chairman of the Board of Directors, David Moss, our Chief Financial Officer and Treasurer and Mark Lowdell, our Chief Scientific Officer. Because our officers and directors also own Immune Ventures there may be an inherent conflict of interest which could result in unanticipated actions that adversely affect us.
Because our officers and directors also own Immune Ventures there may be an inherent conflict of interest which could result in unanticipated actions that adversely affect us. Changes in U.S. patent law could diminish the value of patents in general, thereby impairing our ability to protect our products.
We cannot predict the likelihood of any claims or actions being brought against us or the amount of any penalties or fines in connection with the Sales. 55 Risks Related to our Common Stock We do not intend to pay dividends for the foreseeable future.
We cannot predict with certainty the long-term effects of the new unitary patent system. 51 Risks Related to our Common Stock We do not intend to pay dividends for the foreseeable future.
The effects of competition, intellectual property disputes, market acceptance, and FDA regulations preclude us from forecasting revenues or income with certainty or even confidence. If we fail to protect our intellectual property rights, our ability to pursue the development of our technologies and products would be negatively affected.
The effects of competition, intellectual property disputes, market acceptance, and FDA regulations preclude us from forecasting revenues or income with certainty or even confidence. We have incurred losses since inception and anticipate that we will continue to incur losses for the foreseeable future. We are not currently profitable, and we may never achieve or sustain profitability.
The issuance of additional securities in the future will dilute the percentage ownership of then current stockholders. Anti-takeover provisions in our stockholder rights plan could make a third-party acquisition of us difficult. We have a stockholder rights plan that may have the effect of discouraging unsolicited takeover proposals.
The issuance of additional securities in the future will dilute the percentage ownership of then current stockholders.
The United States and several other jurisdictions are considering, or have already enacted, a number of legislative and regulatory proposals to change the healthcare system in ways that could affect our ability to sell any of our products profitably, if approved.
In the U.S. and some foreign jurisdictions, there have been a number of adopted and proposed legislative and regulatory changes regarding the healthcare system that could prevent or delay regulatory approval of our drug candidates, restrict or regulate post-marketing activities and affect our ability to profitably sell any of our drug candidates for which we obtain regulatory approval.
We have a limited operating history and expect to incur significant additional operating losses. We are an early-stage company formed in September 2015 and have only a limited operating history. Therefore, there is limited historical financial information upon which to base an evaluation of our performance.
We were formed in September 2015 and have only a limited operating history and have incurred losses since our formation. We continue to incur significant development and other expenses related to our ongoing operations.
Removed
Our ability to generate cash depends on a number of factors, some of which are beyond our control, and any failure to meet our debt obligations would have a material adverse effect on our business, financial condition, cash flows and results of operations and could cause the market value of our common stock to decline.
Added
As a result, we may not complete the development and commercialization of our product candidates or develop new product candidates and have substantial doubt about our ability to continue as a going concern. ● Our ability to successfully engage with, and satisfactorily respond to, requests for information from the FDA in the future. ● We have incurred losses since inception and anticipate that we will continue to incur losses for the foreseeable future.
Removed
Prevailing economic conditions and financial, business and other factors, many of which are beyond our control, may affect our ability to make payments on our debt.
Added
These competitors may successfully market products that compete with our products, successfully identify drug candidates or develop products earlier than we do, or develop products that are more effective, have fewer side effects or cost less than our products, if any.
Removed
If we do not generate sufficient cash flow to satisfy our debt obligations, we may have to undertake alternative financing plans, such as refinancing or restructuring our debt, selling assets, reducing or delaying capital investments or seeking to raise additional capital. Alternatively, we may also attempt to refinance certain of our debt, for example, to extend maturities.
Added
We compete with established pharmaceutical and biotechnology companies that are pursuing other forms of treatment for the same indications we are pursuing and that have greater financial and other resources. Other companies may succeed in developing products earlier than us, obtaining FDA approval for products more rapidly, or developing products that are more effective than our product candidates.
Removed
Our ability to restructure or refinance our debt will depend on the capital markets and our financial condition at such time. If we are unable to access the capital markets, whether because of the condition of those capital markets or our own financial condition or reputation within such capital markets, we may be unable to refinance our debt.
Added
As a result, we are not and have never been profitable and have incurred losses in each period since our inception, resulting in substantial doubt in our ability to continue as a going concern. We reported a net loss of $42.1 million and $30.0 million for the years ended December 31, 2024 and 2023, respectively.
Removed
In addition, any refinancing of our debt could be at higher interest rates and may require us to comply with more onerous covenants, which could further restrict our business operations.
Added
As of December 31, 2024 and 2023, we had cash and cash equivalents of $20.9 million and $35.8 million, respectively.
Removed
Our inability to generate sufficient cash flow to satisfy our debt obligations or to refinance our obligations on commercially reasonable terms, or at all, could have a material adverse effect on our business, financial condition, cash flows and results of operations and could cause the market value of our common stock and/or debt securities to decline.
Added
We expect to continue to incur significant losses for the foreseeable future, and we expect these losses to increase as we continue our research and development of, and seek regulatory approvals for, our product candidates and now that we are no longer an emerging growth company, as defined in Section 2(a) of the Securities Act of 1933, as amended.
Removed
Our ability to continue to reduce our indebtedness will depend upon factors including our future operating performance, our ability to access the capital markets to refinance existing debt and prevailing economic conditions and financial, business and other factors, many of which are beyond our control.

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Item 5. Market for Registrant's Common Equity

Market for Common Equity — stock, dividends, buybacks

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Biggest changeAny decisions as to future payment of cash dividends will depend on our earnings and financial position and such other factors as the Board of Directors deems relevant.
Biggest changeAny decisions as to future payment of cash dividends will depend on our earnings and financial position and such other factors as the Board of Directors deems relevant. Securities Authorized for Issuance Under Equity Compensation Plans Information about our equity compensation plans in Item 12 of Part III of this Annual Report is incorporated herein by reference.
ITEM 5. MARKET FOR REGISTRANT’S COMMON EQUITY, RELATED STOCKHOLDER MATTERS AND ISSUER PURCHASES OF EQUITY SECURITIES Common Stock Our common stock trades under the symbol “INMB” on the Nasdaq and has been publicly traded since February 4, 2019. Prior to this time, there was no public market for our common stock.
ITEM 5. MARKET FOR REGISTRANT’S COMMON EQUITY, RELATED STOCKHOLDER MATTERS AND ISSUER PURCHASES OF EQUITY SECURITIES Common Stock Our common stock trades under the symbol “INMB” on The Nasdaq Capital Market and has been publicly traded since February 4, 2019. Prior to this time, there was no public market for our common stock.
As of December 31, 2023, there were 26 holders of record of our common stock. Because shares of our common stock are held by depositories, brokers and other nominees, the number of beneficial holders of our shares is substantially larger than the number of record holders.
As of December 31, 2024, there were 28 holders of record of our common stock. Because shares of our common stock are held by depositories, brokers and other nominees, the number of beneficial holders of our shares is substantially larger than the number of record holders.
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Recent Sales of Unregistered Equity Securities None. Issuer Purchases of Equity Securities None.

Item 7. Management's Discussion & Analysis

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

33 edited+53 added−35 removed55 unchanged
Biggest changeThe decrease in other expense is due to the Company earning higher interest income from money market investments in 2023 ($1.3 million higher) partially offset by higher interest expense on the Company’s debt in 2023 ($0.3 million higher). 66 Liquidity and Capital Resources Liquidity is the ability of a company to generate funds to support its current and future operations, satisfy its obligations and otherwise operate on an ongoing basis.
Biggest changeLiquidity and Capital Resources Liquidity is the ability of a company to generate funds to support its current and future operations, satisfy its obligations and otherwise operate on an ongoing basis. We incurred a net loss of $42,082,000 and $30,008,000 for the years ended December 31, 2024 and 2023, respectively.
We anticipate that our expenses will increase substantially as we: ● continue research and development, including preclinical and clinical development of our existing product candidates; ● potentially seek regulatory approval for our product candidates; 63 ● seek to discover and develop additional product candidates; ● establish a commercialization infrastructure and scale up our manufacturing and distribution capabilities to commercialize any of our product candidates for which we may obtain regulatory approval; ● seek to comply with regulatory standards and laws; ● maintain, leverage and expand our intellectual property portfolio; ● hire clinical, manufacturing, scientific and other personnel to support our product candidate’s development and future commercialization efforts; ● add operational, financial and management information systems and personnel; and ● incur additional legal, accounting and other expenses in operating as a public company.
We anticipate that our expenses will increase substantially as we: ● continue research and development, including preclinical and clinical development of our existing product candidates; ● potentially seek regulatory approval for our product candidates; 61 ● seek to discover and develop additional product candidates; ● establish a commercialization infrastructure and scale up our manufacturing and distribution capabilities to commercialize any of our product candidates for which we may obtain regulatory approval; ● seek to comply with regulatory standards and laws; ● maintain, leverage and expand our intellectual property portfolio; ● hire clinical, manufacturing, scientific and other personnel to support our product candidate’s development and future commercialization efforts; ● add operational, financial and management information systems and personnel; and ● incur additional legal, accounting and other expenses in operating as a public company.
Significant management judgment is required in the forecast of future operating results that are used in the preparation of expected undiscounted cash flows. 64 IPR&D assets are considered to be indefinite-lived until the completion or abandonment of the associated research and development projects. During the period the assets are considered indefinite-lived, they are tested for impairment.
Significant management judgment is required in the forecast of future operating results that are used in the preparation of expected undiscounted cash flows. 62 IPR&D assets are considered to be indefinite-lived until the completion or abandonment of the associated research and development projects. During the period the assets are considered indefinite-lived, they are tested for impairment.
The Australian research and development tax incentive is recognized when there is reasonable assurance that the incentive will be received, the relevant expenditure has been incurred and the amount of the consideration can be reliably measured. 62 Substantially all of our research and development expenses to date have been incurred in connection with our current and future product candidates.
The Australian research and development tax incentive is recognized when there is reasonable assurance that the incentive will be received, the relevant expenditure has been incurred and the amount of the consideration can be reliably measured. 60 Substantially all of our research and development expenses to date have been incurred in connection with our current and future product candidates.
The increase in research and development expenses during the year ended December 31, 2023 compared to 2022 is mainly due to the Company incurring $1.8 million of higher costs in connection with our INKmune clinical trials, $1.2 million higher costs with our Alzheimer’s clinical trial, $0.7 million higher internal costs and $0.5 million lower accrued R&D rebate, partially offset by $1.0 million lower of preclinical and other expenses.
The increase in research and development expenses during the year ended December 31, 2024 compared to 2023 is mainly due to the Company incurring $9.9 million higher costs with our Alzheimer’s clinical trial, $1.3 million of higher costs in connection with our INKmune/CORDStrom clinical trials, $0.7 million higher internal costs and $1.2 million lower accrued R&D rebate, partially offset by $0.3 million lower of preclinical and other expenses.
Our cash and cash equivalents were $35.8 million and total current assets were $21.5 million at December 31, 2023, which the Company is projecting will be insufficient to sustain its operations through one year following the date that the financial statements are issued. Additional capital may not be available on reasonable terms, if at all.
Our cash and cash equivalents were $20.9 million and total current assets were $22.7 million at December 31, 2024, which the Company is projecting will be insufficient to sustain its operations through one year following the date that the financial statements are issued. Additional capital may not be available on reasonable terms, if at all.
Our research and development expense primarily consist of: ● clinical trial and regulatory-related costs; ● expenses incurred under agreements with investigative sites and consultants that conduct our clinical trials; ● manufacturing and testing costs and related supplies and materials; and ● employee-related expenses, including salaries, benefits, travel and stock-based compensation The following table summarizes our research and development expenses by product candidate for the periods indicated (in thousands): Year Ended December 31, 2023 2022 External Costs DN-TNF – Alzheimer’s disease $ 13,817 $ 12,573 INKmune – High Risk MDS/AML & Prostate Cancer 3,296 1,495 Preclinical and other programs 921 1,903 Accrued research and development rebate (3,040 ) (3,531 ) Total external costs 14,994 12,440 Internal Costs 5,279 4,627 $ 20,273 $ 17,067 We typically use our employee resources across our development programs.
Our research and development expense primarily consist of: ● clinical trial and regulatory-related costs; ● expenses incurred under agreements with investigative sites and consultants that conduct our clinical trials; ● manufacturing and testing costs and related supplies and materials; and ● employee-related expenses, including salaries, benefits, travel and stock-based compensation The following table summarizes our research and development expenses by product candidate for the periods indicated (in thousands): Year Ended December 31, 2024 2023 External Costs DN-TNF – Alzheimer’s disease $ 23,765 $ 13,817 INKmune (High Risk MDS/AML & Prostate Cancer) and CORDStrom 4,589 3,296 Preclinical and other programs 611 921 Accrued research and development rebate (1,823 ) (3,040 ) Total external costs 27,142 14,994 Internal Costs 6,024 5,279 $ 33,166 $ 20,273 We typically use our employee resources across our development programs.
The change in our net operating assets and liabilities was primarily due to an increase in research and development tax credit receivable of $3.2 million and an increase in prepaid expenses and other current assets of $1.7 million, partially offset by an increase in accounts payable and accrued liabilities of $1.5 million.
The change in our net operating assets and liabilities was primarily due to a decrease in prepaid expenses of $1.2 million, a decrease in research and development tax rebate receivable of $0.7 million and a decrease in other tax receivable of $0.3 million, partially offset by a decrease of $1.4 in accounts payable and accrued liabilities.
Finally, several months after all the data are analyzed, the Company plans an end-of-phase II meeting with the FDA to finalize plans for the pivotal Phase III trial. The Company plans to apply for an accelerated pathway during 2024. XPro for treatment of AD may be eligible for one or both accelerated approval pathways.
Finally, several months after all the data are analyzed, the Company plans an end-of-phase II meeting with the FDA to finalize plans for the pivotal Phase III trial. XPro for treatment of AD may be eligible for one or both accelerated approval pathways. We expect to be eligible for Break Through status after completion of the Phase II in 2025.
Research and Development Research and development expenses increased to $20.3 million for the year ended December 31, 2023 from $17.1 million for the year ended December 31, 2022.
Research and Development Research and development expenses increased to $33.2 million for the year ended December 31, 2024 from $20.3 million for the year ended December 31, 2023.
As of December 31, 2023, we had cash and cash equivalents of $35,848,000. We anticipate that operating losses and net cash used in operating activities will increase over the next few years as we advance our products under development.
We anticipate that operating losses and net cash used in operating activities will increase over the next few years as we advance our products under development.
Net Cash Provided by Financing Activities During the year ended December 31, 2023, the Company sold 75,697 shares of its common stock for net proceeds of $0.8 million under the Company’s ATM program with BTIG. During the year ended December 31, 2023, the Company repaid $5 million of its debt.
During the year ended December 31, 2023, the Company sold 75,697 shares of its common stock for net proceeds of $0.8 million under the Company’s ATM program.
The primary end-point will be Early/mild Alzheimer’s Cognitive Composite (“EMACC”), a validated cognitive measure that is more sensitive than traditional end-points used in many studies of patients with early AD. The AD program is open in the United States, Australia, Canada, the United Kingdom, France, Germany, Spain, Czech Republic and Slovakia.
The primary end-point will be Early/mild Alzheimer’s Cognitive Composite (“EMACC”), a validated cognitive measure that is more sensitive than traditional end-points used in many studies of patients with early AD.
This is how long are the number of mlNK cells in patients blood compared to baseline. There are 3 important variables to tumor response: i) blood PSA changes; ii) change in PMSA scan and iii) change in circulating tumor DNA (ctDNA). Ideally, the levels of all three variables decrease with treatment.
The most important immunologic response variable is related to memory like NK cell persistence. This is how long are the number of mlNK cells in patients blood compared to baseline. There are 3 important variables to tumor response: i) blood PSA changes; ii) change in PMSA scan and iii) change in circulating tumor DNA (ctDNA).
Our recurring net losses and negative cash flows from operations, as well as forecast of continued losses and negative cash flows from operations, raised substantial doubt regarding our ability to continue as a going concern within one year after the issuance of our consolidated financial statements for the year ended December 31, 2023.
As of December 31, 2024, the cash balance held by our foreign subsidiaries with currencies other than the United States dollar was approximately $0.1 million. 64 Our recurring net losses and negative cash flows from operations, as well as forecast of continued losses and negative cash flows from operations, raised substantial doubt regarding our ability to continue as a going concern within one year after the issuance of our consolidated financial statements for the year ended December 31, 2024.
We incurred a net loss of $30,008,000 and $27,299,000 for the years ended December 31, 2023 and 2022, respectively. Net cash used in operating activities was $11,980,000 and $22,686,000 for the years ended December 31, 2023 and 2022, respectively. Since inception, we have funded our operations primarily with proceeds from the sales of our common stock.
Net cash used in operating activities was $33,361,000 and $11,980,000 for the years ended December 31, 2024 and 2023, respectively. Since inception, we have funded our operations primarily with proceeds from the sales of our common stock. As of December 31, 2024, we had cash and cash equivalents of $20,922,000.
We expect to continue to incur significant losses for the foreseeable future, and we expect these losses to increase as we continue our research and development of, and seek regulatory approvals for, our product candidates.
As of December 31, 2024 and 2023, we had cash and cash equivalents of $20.9 million and $35.8 million, respectively. We expect to continue to incur significant losses for the foreseeable future, and we expect these losses to increase as we continue our research and development of, and seek regulatory approvals for, our product candidates.
Operating activities used $22.7 million of cash for the year ended December 31, 2022, primarily resulting from our net loss of $27.3 million, a net cash outflow of $2.9 million for changes in our net operating assets and liabilities, and non-cash stock-based compensation charges of $7.1 million.
Operating activities used $33.4 million of cash for the year ended December 31, 2024, primarily resulting from our net loss of $42.1 million, partially offset by a net cash inflow of $1.0 million for changes in our net operating assets and liabilities, and non-cash stock-based compensation charges of $7.6 million.
Our recurring net losses and negative cash flows from operations raised substantial doubt regarding our ability to continue as a going concern within one year after the issuance of our consolidated financial statements for the year ended December 31, 2023.
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, if any. 59 Our recurring net losses and negative cash flows from operations raise substantial doubt regarding our ability to continue as a going concern within one year after the issuance of our consolidated financial statements for the year ended December 31, 2024.
In the future, we may develop the asset in a wide variety of therapeutic areas, with a variety of delivery techniques by ourselves or in conjunction with partners. 65 Results of Operations Comparison of the Years Ended December 31, 2023 and December 31, 2022 Year Ended (in thousands) December 31, 2023 December 31, 2022 Change Revenues $ (155 ) $ (374 ) $ 219 General and Administrative 9,623 9,258 365 Research and Development 20,273 17,067 3,206 Other Expense, net 267 1,348 (1,081 ) Net loss $ 30,008 $ 27,299 $ 2,709 Revenues During 2023 and 2022, the Company sold MSC’s to one customer and recognized $155,000 and $374,000 of revenues, respectively.
In the future, we may develop the asset in a wide variety of therapeutic areas, with a variety of delivery techniques by ourselves or in conjunction with partners. 63 Results of Operations Comparison of the Years Ended December 31, 2024 and December 31, 2023 Year Ended (in thousands) December 31, 2024 December 31, 2023 Change Revenues $ 14 $ 155 $ (141 ) General and Administrative 9,483 9,623 (140 ) Research and Development 33,166 20,273 12,893 Other (Income) Expense, net (553 ) 267 (820 ) Net loss $ 42,082 $ 30,008 $ 12,074 Revenues During 2024 and 2023, the Company sold MSC’s to one customer in the United Kingdom and recognized $14,000 and $155,000 of revenues, respectively.
We discuss factors that we believe could cause or contribute to these differences below and elsewhere in this Form 10-K, including those set forth under “Risk Factors” and “Forward-Looking Statements.” Overview We are a clinical-stage immunology company focused on developing drugs that may reprogram the patient’s innate immune system to treat disease.
We discuss factors that we believe could cause or contribute to these differences below and elsewhere in this Form 10-K, including those set forth under “Risk Factors” and “Forward-Looking Statements.” Overview Our objective is to develop and commercialize our product candidates to treat diseases where the innate immune system is dysfunctional causing or contributing to the patient’s disease.
The Company received a $2.9M USD award from the National Institute of Mental Health (“NIMH”) to treat TRD with XPro. The blinded, randomized Phase II trial will use biomarkers of peripheral inflammation to select patients with TRD for enrollment. Patients will be treated for 6 weeks. Primary end-points include both clinical and neuroimaging measures.
The blinded, randomized Phase II trial will use biomarkers of peripheral inflammation to select patients with TRD for enrollment. Patients will be treated for 6 weeks. Primary end-points include both clinical and neuroimaging measures. The TRD trial is expected to start enrollment during 2025.
Critical Accounting Policies and Significant Judgments and Estimates This management’s discussion and analysis of our financial condition and results of operations is based on our financial statements, which we have prepared in accordance with accounting principles generally accepted in the United States.
Other income, net Other expense consists primarily of interest expense incurred on debt, partially offset by interest income from a money market investment. Critical Accounting Estimates This management’s discussion and analysis of our financial condition and results of operations is based on our financial statements, which we have prepared in accordance with accounting principles generally accepted in the United States.
General and Administrative General and administrative expenses were $9.6 million for the year ended December 31, 2023, compared to $9.3 million for the year ended December 31, 2022.
General and Administrative General and administrative expenses were $9.5 million for the year ended December 31, 2024, compared to $9.6 million for the year ended December 31, 2023. The decrease in general and administrative expenses is due to lower travel expense.
The Term loan is payable in 2024. 67 Cash Flows The following table provides information regarding our cash flows for the years ended December 31, 2023 and 2022: Year Ended December 31, 2023 2022 Net cash used in operating activities $ (11,980 ) $ (22,686 ) Net cash provided by financing activities (4,225 ) 729 Impact on cash from foreign currency translation (100 ) (700 ) Net decrease in cash and cash equivalents $ (16,305 ) $ (22,657 ) Net Cash Used in Operating Activities Our cash used in operating activities was primarily driven by our net loss.
During February 2025, the Company entered into a letter agreement with its lenders whereby its term loan was terminated. 65 Cash Flows The following table provides information regarding our cash flows for the years ended December 31, 2024 and 2023: Year Ended December 31, 2024 2023 Net cash used in operating activities $ (33,361 ) $ (11,980 ) Net cash used in (provided by) financing activities 18,211 (4,225 ) Impact on cash from foreign currency translation 224 (100 ) Net decrease in cash and cash equivalents $ (14,926 ) $ (16,305 ) Net Cash Used in Operating Activities Our cash used in operating activities was primarily driven by our net loss.
Because of the modified Bayesian design, the Company estimates the trial will be completely enrolled 1H25 with top-line data available 6 months later. Topline data is divided into immunologic and tumor response variables. The most important immunologic response variable is related to memory like NK cell persistence.
Biomarker data from the patients will be visible as patients are treated. The Company will report data from each cohort as it becomes available. Because of the modified Bayesian design, the Company estimates the trial will be completely enrolled 1H25 with top-line data available 6 months later. Topline data is divided into immunologic and tumor response variables.
Six months after the last patient is enrolled, top line cognition data with EMACC will be available. Secondary end-points which include blood biomarker, neuroimaging and additional neuropsychiatric end-points will be available after data base lock 2-3 months after top line data.
Topline data of EMACC is expected to be reported in June followed by secondary end-points which include blood biomarker, neuroimaging and additional neuropsychiatric end-points which should be available 2-3 months after top line data.
Any of these events could significantly harm our business, financial condition and prospects. ATM Sales Agreement During July 2023, the Company sold 75,697 shares of its common stock at an average price of $ 10.56 per share under the ATM program. The aggregate net proceeds were approximately $ 775,000 after offering expenses.
Any of these events could significantly harm our business, financial condition and prospects. ATM Sales Agreement During the year ending December 31, 2024, the Company sold 247,126 shares of common stock at an average price of $9.85 for gross proceeds of approximately $2.4 million under the at the market offerings.
This is a large patient population. The role of TNF and anti-TNF therapeutics was explored in a small open label clinical trial by Prof. Andrew Miller, MD of Emory University demonstrated the patients have elevated TNF levels and treatment with infliximab treated their depression (Miller, 2011).
Effective therapy for TRD is a large unmet need. Twenty percent of patients with a Major Depressive Disorder have TRD. Once third of TRD patients have peripheral biomarkers to inflammation (elevated CRP). This is a large patient population. The role of TNF and anti-TNF therapeutics was explored in a small open label clinical trial by Prof.
INKmune is being developed to treat NK sensitive hematologic malignancies and solid tumors. 59 We believe our DN-TNF platform can be used as a CNS (“central nervous system”) therapy to target glial activation to prevent progression of Alzheimer’s disease (“AD”); to target neuroinflammation in treatment resistant depression (“TRD”); as a drug to prevent muscle degeneration, prevent fibrosis and promote muscle regeneration in Duchene muscular dystrophy (“DMD”); and as a cancer therapy to reduce resistance in immunotherapy.
Concurrently, the company will also seek to submit MAAs to the EU and United Kingdom in 2026. 57 We believe our DN-TNF platform can be used as a CNS (“central nervous system”) therapy to target glial activation to prevent progression of Alzheimer’s disease (“AD”); to target neuroinflammation in treatment resistant depression (“TRD”).
We may choose to take advantage of some but not all of these reduced burdens. Components of Operating Results Operating Expenses Research and Development Research and development expense consists of expenses incurred while performing research and development activities to discover and develop our product candidates.
To date, the Company has relied on equity and debt financing to fund its operations. Components of Operating Results Operating Expenses Research and Development Research and development expense consists of expenses incurred while performing research and development activities to discover and develop our product candidates.
We do not expect this 6 month trial to provide survival data. We continue to incur significant development and other expenses related to our ongoing operations. As a result, we are not and have never been profitable and have incurred losses in each period since our inception, resulting in substantial doubt in our ability to continue as a going concern.
As a result, we are not and have never been profitable and have incurred losses in each period since our inception, resulting in substantial doubt in our ability to continue as a going concern. We reported a net loss of $42.1 million and $30.0 million for the years ended December 31, 2024 and 2023, respectively.
We currently do not hedge foreign currencies but will continue to assess whether that strategy is appropriate. As of December 31, 2023, the cash balance held by our foreign subsidiaries with currencies other than the United States dollar was approximately $0.5 million.
We currently do not hedge foreign currencies but will continue to assess whether that strategy is appropriate.
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We believe this may be done by targeting cells of the innate immune system that cause acute and chronic inflammation and are involved in immune dysfunction associated with chronic diseases such as cancer and neurodegenerative diseases. The Company’s drugs are in clinical trials and have not been approved by a regulatory authority.
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Innate immune dysfunction can occur for a variety of reasons including genetics, lifestyle, and other factors. However, age plays a significant role in the development of immune dysfunction. Innate immune dysfunction can be seen in cancer where Natural Killer (“NK”) cells are impaired and facilitate a tumor’s evasion of the immune system and subsequent disease progression.
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The Company has two therapeutic platforms – a dominant-negative TNF platform (“DN-TNF”, “XPro™”, “XPro1595™” or “ pegipanermin” ) and a Natural Killer (“NK”, or “INKmune™”) platform. The DN-TNF platform neutralizes soluble TNF (“sTNF”) without affecting trans-membrane TNF (“tmTNF”) or TNF receptors -TNFR1 and TNFR2.
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Chronic inflammation is implicated in neurologic and metabolic diseases where it impairs the innate immune system. Our primary focus continues to be treatment of cancer with INKmune and treatment of Alzheimer’s Disease (“AD”) and Treatment Resistant Depression (“TRD”) with XPro1595.
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This unique biologic mechanism differentiates the DN-TNF drugs from currently approved non-selective TNF inhibitors that inhibit both sTNF and tmTNF. Protecting the function of tmTNF and TNF receptors while neutralizing the function of sTNF is a potent anti-inflammatory strategy that does not cause immunosuppression or demyelination which occur in the currently approved non-selective TNF inhibitors.
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We have added CORDStrom, a pooled, human umbilical cord mesenchymal stem cell product to treat recessive dystrophic epidermolysis bullosa (RDEB), a pediatric orphan disease caused by mutations in the COL7A1 gene that results in a debilitating disease of skin blistering, dysphagia and failure to thrive with chronic wound problems that often results in fatal squamous cell carcinoma.
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Currently approved non-selective TNF inhibitors treat autoimmune disease, but are contraindicated in patients with infection, cancer and neurologic diseases because they increase the risk of infection, cancer and demyelinating neurologic diseases, respectively; these safety problems are due to off-target effects on inhibiting tmTNF. The NK platform targets the dysfunctional natural killer cells in patients with cancer.
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XPro1595 (“XPro”), targets Alzheimer’s Disease and TRD. XPro for AD has completed Phase I trials and a Phase II trial has completed enrollment of patients at clinical sites in the United Kingdom, EU, Australia and Canada. Patients are currently being treated with XPro for Early AD as part of that clinical trial. TRD is being prepared for Phase II trials.
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NK cells are part of the normal immunologic response to cancer with important roles in immunosurveillance to prevent cancer and in preventing relapse by eliminating residual disease. Residual disease is the cancer left behind after therapy is finished. Residual disease can grow to cause relapse.
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We expect to start a pivotal global registration trial in patients with AD after the results of the Phase II trial have been analyzed. The INKmune program is in an open label Phase II trial in metastatic castrate resistant prostate cancer (mCRPC). CORDStrom for the treatment of children with RDEB has completed a pivotal blinded randomized cross-over trial.
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The mechanism by which INKmune improves the ability of the patient’s NK cells to kill their cancer is complex. The NK cells of cancer patients lose the ability to bind and kill cancer cells. A measure of NK cell binding to cancer cells is avidity.
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The data will be submitted for a marketing authorization by filing a Biologics License Application (BLA) with the FDA in the US which is anticipated in late 2025 or early 2026.
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The higher the avidity, the greater the bond between the NK cell to cancer cell and thus the greater NK killing of cancer cells. INKmune increases NK avidity and further improves mitochondrial function and upregulates nutrient receptors. These metabolic changes may help the INKmune primed NK cell to function in the hostile tumor microenvironment and persist much longer.
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Afterwards, the company intends to file a Marketing Authorization Application (MAA) in the United Kingdom and EU. 55 CORDStrom, developed by INmune Bio circa 2020, represents a breakthrough in mesenchymal stem cell technology.
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These mechanisms improve the ability of INKmune primed NK cells to overcome the immune evasion of the patient’s cancer cells. We believe INKmune is best used to eliminate residual disease after the patient has completed other cancer therapies. Both the DN-TNF platform and the INKmune platform can be used to treat multiple diseases.
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The CORDStrom platform leverages, among other things, proprietary screening, pooling and expansion techniques to create off-the-shelf, allogeneic, pooled human umbilical cord -derived mesenchymal stromal cells (HucMSCs) as medicines to treat complex inflammatory diseases.
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The DN-TNF platform will be used as an immunotherapy for the treatment of cancer and neurodegenerative disease.
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CORDStrom products are designed to provide high-quality, off-the-shelf, batch-to-batch consistent, scalable, cGMP manufactured, potent cellular medicines that can be produced at low cost and with repeatable specification independent of donor characteristics.
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The primary focus of the company’s development efforts for XPro is AD. The next indication to be developed with XPro will be TRD. Treatment of DMD and cancer will occur when partners for the programs are found. The drug is named differently for the oncology and CNS indications; INB03™ or XPro, respectively, but it is the same drug product.
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Initially developed at the INKmune manufacturing facilities utilizing United Kingdom academic grant funding, CORDStrom is a product platform that shows promise as a therapy for RDEB and many other debilitating conditions.
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For DMD, the company is exploring DN-TNF compounds that is optimized for the treatment of DMD. This novel compound has the same mechanism of action but has novel IP protection. In each case, we believe neutralizing sTNF is a cornerstone to the treatment of these diseases.
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While the first generation CORDStrom product is agnostic to indication, the platform enables creation of indication-specific products, which can be tuned for optimization of anti-inflammatory, immunomodulatory, wound healing, and other characteristics.
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As an immunotherapy for cancer, we are using INB03 to neutralize sTNF produced by HER2+ trastuzumab resistant breast cancers to reverse resistance to targeted therapy. sTNF produced by the tumor causes an up-regulation of MUC4 express causing steric hindrance of trastuzumab binding to the HER receptor on HER2+ breast cancer cells. Without binding, trastuzumab based therapies are not effective.
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The CORDStrom product platform shares many similarities, including starting materials, equipment, and procedures, with the Company’s INKmune oncology product, enabling the Company to leverage economies of scale, experienced staff, and other resources to strategically manufacture both products in a rotational campaign with resource and environmental efficiencies.
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Neutralizing sTNF reverses MUC4 expression converting a trastuzumab resistant breast cancer cell into a trastuzumab sensitive breast cancer cell. In addition, INB03 may change the immunobiology of the tumor microenvironment by decreasing the number of immunosuppressive myeloid cells, both myeloid derived suppressor cells and tumor active macrophages, and increasing the number of cytotoxic lymphocytes and phagocytic macrophages in the TME.
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Children with Recessive Dystrophic Epidermolysis Bullosa (RDEB) have skin that is damaged by even the smallest amount of friction which causes severe blistering, deep wounds, and scars. It is caused by a fault in a gene that makes collagen, a protein that holds the skin layers together.
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The Company has completed an open label dose escalation trial in cancer patients with metastatic solid tumors that have failed multiple lines of therapy.
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There are limited options available for treatment, none that adequately meet the needs of patients, and the condition gets worse over time with most children reliant on a wheelchair as they move into their teenage years.
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The pre-clinical data in MUC4+ expressing tumors and the clinical trial informs the design of a future Phase II trial by demonstrating that INB03 was safe and well tolerated, defined the dose of INB03 to carry into Phase II trials, and demonstrated a pharmacodynamic end-point.
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Many of those with an RDEB diagnosis will also go on to develop aggressive life-threatening skin cancer in adulthood caused by the accumulated damage to their skin. The Company estimates roughly 2,000 people suffer from RDEB in the US, United Kingdom and EU representing a large unmet opportunity to potentially provide routine clinical care to these children.
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The company does not plan to commence a Phase II trial in patients with advanced MUC4+ expressing cancer until a partner can be found. Likewise, we believe the DN-TNF platform can be used to treat selected neurodegenerative diseases by modifying the brain microenvironment (“BME”).
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Since 2020, the Company has supplied CORDStrom HucMSCs as an investigational medical product to the Great Ormond Street Hospital (GOSH), London, in connection with the MissionEB study, which was primarily funded by a grant from the National Institute for Health and Care Research (NIHR) in the United Kingdom.
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All patients will be offered to stay on therapy for at least 12 months in an extension trial. Clinical and biomarker data will be collected during the extension trial. 60 There are at least 4 clinical milestones associated with the Phase II trial in AD. Enrollment of 201 patients in the Phase II AD trial should be complete by mid-year.
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INmune Bio was compensated for CORDStrom used in the trial and was not a sponsor of the Mission EB study.
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The Company plans to submit of Fast Track status in 2024. We expect to be eligible for Break Through status after completion of the Phase II in 2025. Effective therapy for TRD is a large unmet need. Twenty percent of patients with a Major Depressive Disorder have TRD. Once third of TRD patients have peripheral biomarkers to inflammation (elevated CRP).
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Investigators recently concluded a double blinded, placebo-controlled arm of the study, which evaluated the safety and efficacy of CORDStrom in 30 pediatric patients (less than 16 years old) in the United Kingdom with intermediate and severe RDEB using a novel cross-over clinical trial design.
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The final trial design is ongoing and discussions with the FDA are not complete. The Company received authorization to initiate a clinical trial in AD in the US during January 2024. The TRD trial is expected to start enrollment after the AD Phase II trial finishes patient enrollment.
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Patients were randomized to CORDStrom or placebo arms and received 2, intravenous infusions two weeks apart and then followed for 9 months. Each child then crossed over to the other arm and received two doses of placebo or CORDStrom two weeks apart with a further 9-month follow-up.
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Biomarker data from the patients will be visible as patients are treated. The Company will report data from each cohort as it becomes available. In addition to clinical data, the Company will communicate when the Phase I portion of the trial has completely enrolled. This is expected in September 2024.
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All patients were treated as day-cases and no CORDStrom related serious adverse events were reported through the study. Top-line results showed the treatment was easily administered, well tolerated and there were beneficial effects across all types of patients receiving CORDStrom with respect to Itch Man Scale, iscorEB clinician score and iscorEB skin involvement.
Removed
We reported a net loss of $30.0 million and $27.3 million for the years ended December 31, 2023 and 2022, respectively. As of December 31, 2023 and 2022, we had cash and cash equivalents of $35.8 million and $52.2 million, respectively.
Added
Most notably, CORDStrom significantly reduced itch scores as measured by the Itch Man Scale. In patients with the most severe disease activity, CORDStrom reduced itch at 3 months and led to a sustained reduction of over 27% at 6 months. These results demonstrate a clinically meaningful reduction in itch severity sustained over time.
Removed
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, if any.
Added
Intermediate group patients showed a broader range of improvements, including reduced skin involvement and less pain as well as large reduction in itch. The younger patients (less than 10 years old) showed improvements in skin score, indicating better skin integrity and reduced disease activity.
Removed
To date, the Company has relied on equity and debt financing to fund its operations. As a company with less than $1.235 billion in revenue during our last fiscal year, we qualify as an “emerging growth company” under the JOBS Act.
Added
Interviews with patients and caregivers on completing follow up strongly support the clinical benefits of the therapy; both caregivers and patients were able to correctly identify which treatment had been CORDStrom and which had been placebo.
Removed
As an emerging growth company, we may take advantage of specified reduced disclosure and other requirements that are otherwise applicable generally to public companies.

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