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What changed in Monopar Therapeutics's 10-K — 2022 vs 2023

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Paragraph-level year-over-year comparison of Monopar Therapeutics's 2022 and 2023 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 2023 report.

+317 added−520 removedSource: 10-K (2024-03-28) vs 10-K (2023-03-23)

Top changes in Monopar Therapeutics's 2023 10-K

317 paragraphs added · 520 removed · 216 edited across 5 sections

Item 1. Business

Business — how the company describes what it does

58 edited+42 added−193 removed81 unchanged
Biggest changeResults from clinical studies conducted outside of Japan must be supplemented with at least a bridging clinical study conducted in Japanese patients. 28 Table of Contents In addition to regulations in Europe, Canada, Japan and the U.S., there are a variety of foreign regulations governing clinical studies, commercial distribution and reimbursement of future product candidates which we may be subject to as we pursue regulatory approval and commercialization of Validive, camsirubicin, MNPR-101, or any future product candidates internationally.
Biggest changeIn addition to regulations in Europe, Canada, Japan, Australia and the U.S., there are a variety of foreign regulations governing clinical studies, commercial distribution and reimbursement of future product candidates which we may be subject to as we pursue regulatory approval of the MNPR-101 radiopharmaceutical program, camsirubicin, or any future product candidates internationally. 21 Table of Contents Compliance with Environmental Laws Since we do not have our own laboratory or manufacturing facilities, we do not estimate any annual costs of compliance with environmental laws.
Government Regulation and Product Approval Government authorities in the U.S., at the federal, state and local level, and in other countries extensively regulate, among other things, the research, development, testing, manufacture, quality control, approval, labeling, packaging, storage, record-keeping, promotion, advertising, distribution, post-approval monitoring and reporting, marketing and export and import of products such as those we are developing.
Government Regulation and Product Approval Government authorities in the U.S., at the federal, state and local level, and in other countries such as Australia, extensively regulate, among other things, the research, development, testing, manufacture, quality control, approval, labeling, packaging, storage, record-keeping, promotion, advertising, distribution, post-approval monitoring and reporting, marketing and export and import of products such as those we are developing.
In this study, 52.6% of patients evaluable for tumor progression demonstrated clinical benefit (partial response or stable disease), which was proportional to dose and consistently observed at higher cumulative doses of camsirubicin (>1000 mg/m 2 ).
In this previous study, 52.6% of patients evaluable for tumor progression demonstrated clinical benefit (partial response or stable disease), which was proportional to dose and consistently observed at higher cumulative doses of camsirubicin (>1000 mg/m 2 ).
MNPR-101 Our patent portfolio for our MNPR-101 antibody (huATN-658), as well as its epitope, consists of two issued U.S. composition of matter and their methods of use patents and corresponding (granted and pending) patents and patent applications in twenty-two foreign jurisdictions, including the European Union, Japan, and other Asian countries. These patents are owned by us.
MNPR-101 Our patent portfolio for our MNPR-101 antibody (huATN-658), as well as its epitope, consists of two issued U.S. composition of matter and their methods of use patents and corresponding (granted and pending) patents and patent applications in multiple foreign jurisdictions, including the European Union, Japan, and other Asian countries. These patents are owned by us.
If a complete response letter is issued, the applicant may either resubmit the NDA or BLA, addressing all of the deficiencies identified in the letter, or withdraw the application. 25 Table of Contents If a product receives regulatory approval, the approval may be significantly limited to specific diseases and dosages or the indications for use may otherwise be limited, which could restrict the commercial value of the product.
If a complete response letter is issued, the applicant may either resubmit the NDA or BLA, addressing all of the deficiencies identified in the letter, or withdraw the application. 20 Table of Contents If a product receives regulatory approval, the approval may be significantly limited to specific diseases and dosages or the indications for use may otherwise be limited, which could restrict the commercial value of the product.
We intend to satisfy any disclosure requirement under Item 5.05 of Form 8-K regarding an amendment to, or waiver from, a provision of our Code of Business Conduct and Ethics by posting such information on our website as specified above. 29 Table of Contents
We intend to satisfy any disclosure requirement under Item 5.05 of Form 8-K regarding an amendment to, or waiver from, a provision of our Code of Business Conduct and Ethics by posting such information on our website as specified above. 22 Table of Contents
Based on the encouraging clinical results to date, in September 2021, we commenced an open-label, Phase 1b dose escalation trial of camsirubicin plus growth factor support (pegfilgrastim/G-CSF) in the U.S. as first-line treatment for patients with ASTS. The aim is to administer camsirubicin without restricting cumulative dose, thereby potentially improving efficacy by keeping patients who are responding on treatment.
Based on the previous clinical results, in September 2021, we commenced an open-label, Phase 1b dose escalation trial of camsirubicin plus growth factor support (pegfilgrastim/G-CSF) in the U.S. as first-line treatment for patients with ASTS. The aim is to administer camsirubicin without restricting cumulative dose, thereby potentially improving efficacy by keeping patients who are responding on treatment.
We have a patent for chemical synthesis technology that efficiently converts cardiotoxic “13-keto” anthracyclines such as doxorubicin, daunorubicin, epirubicin, and idarubicin into novel, patentable, and most likely less-cardiotoxic “5-imino-13-deoxy” analogs. A novel chemical composition of an intermediate for this synthesis is also patented.
We have a patent for chemical synthesis technology that efficiently converts cardiotoxic “13-keto” anthracyclines such as doxorubicin, daunorubicin, epirubicin, and idarubicin into novel, patentable, and potentially less-cardiotoxic “5-imino-13-deoxy” analogs. A novel chemical composition of an intermediate for this synthesis is also patented.
International Regulation In addition to regulations in the U.S., there are a variety of foreign regulations governing clinical studies and commercial sales and distribution of our future product candidates.
Other International Regulation In addition to regulations in the U.S. and Australia, there are a variety of foreign regulations governing clinical studies and commercial sales and distribution of our future product candidates.
The patent covering novel, potentially more potent analogs of camsirubicin expires in 2038. We may pursue patent term extensions where appropriate. We have obtained patent protection around the intermediates and process used to manufacture camsirubicin and we expect to obtain Hatch-Waxman exclusivity (applicable to new chemical entities) for 5 years that will prevent generic competition.
The patent covering novel, potentially more potent analogs of camsirubicin expires in 2038. We may pursue patent term extensions where appropriate or let patents lapse. We have obtained patent protection around the intermediates and process used to manufacture camsirubicin and we expect to obtain Hatch-Waxman exclusivity (applicable to new chemical entities) for 5 years that will prevent generic competition.
No growth factor support (G-CSF) was given to patients, and the limiting toxicity was neutropenia. In January 2015, a multi-center open label single arm Phase 2 clinical trial was initiated in doxorubicin-naïve patients with ASTS. This Phase 2 clinical trial enrolled 22 patients and was completed in August 2016.
No growth factor support (G-CSF) was given to patients, and the limiting toxicity was neutropenia. 11 Table of Contents In January 2015, a multi-center open label single arm Phase 2 clinical trial was initiated in doxorubicin-naïve patients with ASTS. This Phase 2 clinical trial enrolled 22 patients and was completed in August 2016.
The IRB also approves the informed consent form that must be provided to each clinical study subject or his or her legal representative and must monitor the clinical study until completed. Human clinical studies are typically conducted in three sequential phases that may overlap or be combined: ● Phase 1.
The IRB also approves the informed consent form that must be provided to each clinical study subject or his or her legal representative and must monitor the clinical study until completed. 18 Table of Contents Human clinical studies are typically conducted in three sequential phases that may overlap or be combined: ● Phase 1.
License, Development and Collaboration Agreements Onxeo S.A. In June 2016, we executed an agreement with Onxeo S.A., a French public company, which gave us the exclusive option to license (on a world-wide exclusive basis) Validive (clonidine hydrocholoride mucobuccal tablet; clonidine HCI MBT) a mucoadhesive tablet of clonidine based on the Lauriad mucoadhesive technology.
In June 2016, we executed an agreement with Onxeo S.A., a French public company, which gave us the exclusive option to license (on a world-wide exclusive basis) Validive (clonidine hydrocholoride mucobuccal tablet; clonidine HCI MBT) a mucoadhesive tablet of clonidine based on the Lauriad mucoadhesive technology.
Additionally, appropriate packaging must be selected and tested, and stability studies must be conducted to demonstrate that the pharmaceutical product candidate does not undergo unacceptable deterioration over its shelf life. 24 Table of Contents U.S.
Additionally, appropriate packaging must be selected and tested, and stability studies must be conducted to demonstrate that the pharmaceutical product candidate does not undergo unacceptable deterioration over its shelf life. U.S.
Under E.U. regulatory systems, marketing applications for pharmaceutical products must be submitted under a centralized procedure to the EMA. The centralized procedure provides for the granting of a single marketing authorization that is valid for all E.U. member states.
Under E.U. regulatory systems, marketing applications for pharmaceutical products are typically submitted under a centralized procedure to the EMA. The centralized procedure provides for the granting of a single marketing authorization that is valid for all E.U. member states.
The process required by the FDA before a non-biological pharmaceutical product may be marketed in the U.S. generally involves the following: 22 Table of Contents ● Completion of preclinical laboratory tests, animal studies and formulation studies according to Good Laboratory Practices (“GLP”), and other applicable regulations; ● Submission to the FDA of an Investigational New Drug application (“IND”), which must become effective before human clinical studies may begin; ● Performance of adequate and well-controlled human clinical studies according to the FDA’s current Good Clinical Practices (“GCP”), to establish the safety, efficacy and optimum dose of the proposed pharmaceutical product for its intended use; ● Submission to the FDA of a New Drug Application (“NDA”) or Biologics License Application (“BLA”), for a new pharmaceutical product; ● Satisfactory completion of an FDA inspection of the manufacturing facility or facilities where the pharmaceutical product is produced to assess compliance with the FDA’s current Good Manufacturing Practice standards (“cGMP:”), to assure that the facilities, methods and controls are adequate to preserve the pharmaceutical product’s identity, strength, quality and purity; ● FDA audits of the preclinical and clinical study sites that generated the data in support of the NDA or BLA; ● FDA review and approval of the NDA; and ● Fulfillment of FDA post-marketing requirements, if any.
The process required by the FDA before a non-biological pharmaceutical product may be marketed in the U.S. generally involves the following: ● Completion of preclinical laboratory tests, animal studies and formulation studies according to Good Laboratory Practices (“GLP”), and other applicable regulations; ● Submission to the FDA of an Investigational New Drug application (“IND”), which must become effective before human clinical studies may begin; ● Performance of adequate and well-controlled human clinical studies according to the FDA’s current Good Clinical Practices (“GCP”), to establish the safety, efficacy and optimum dose of the proposed pharmaceutical product for its intended use; ● Submission to the FDA of a New Drug Application (“NDA”) or Biologics License Application (“BLA”), for a new pharmaceutical product; ● Satisfactory completion of an FDA inspection of the manufacturing facility or facilities where the pharmaceutical product is produced to assess compliance with the FDA’s current Good Manufacturing Practice standards (“cGMP”), to assure that the facilities, methods and controls are adequate to preserve the pharmaceutical product’s identity, strength, quality and purity; ● FDA audits of the preclinical and clinical study sites that generated the data in support of the NDA or BLA; ● FDA review and approval of the NDA; and ● Fulfillment of FDA post-marketing requirements, if any. 17 Table of Contents The lengthy process of seeking required approvals and the continuing need for compliance with applicable statutes and regulations require the expenditure of substantial resources, and approvals are inherently uncertain.
We anticipate hiring additional employees in clinical operations, regulatory affairs and other departments, to help manage our clinical studies, regulatory submissions, and manufacturing to support Validive and camsirubicin program development, business development and corporate strategy.
We anticipate hiring additional employees in clinical operations, regulatory affairs and other departments, to help manage our clinical studies, regulatory submissions, and manufacturing to support the MNPR-101 program and camsirubicin development, business development and corporate strategy.
Although this Phase 1b is designed to determine the maximum tolerated dose of camsirubicin, given the historical dose-dependent anti-tumor response repeatedly demonstrated with doxorubicin, efficacy measurements are being tracked in these patients as the dose is increased.
Although this Phase 1b is designed to determine the maximum tolerated dose of camsirubicin, given the historical dose-dependent anti-tumor response repeatedly demonstrated with doxorubicin, efficacy measurements are being tracked in these patients as the dose is increased. We are presently enrolling patients at the fifth dose level.
Manufacturing We do not currently own or operate manufacturing facilities for the production or testing of Validive, camsirubicin, MNPR-101, MNPR-101-Zr, MPNR-101 RITs or MNPR-202, nor do we have plans to develop our own manufacturing operations in the foreseeable future.
Manufacturing We do not currently own or operate manufacturing facilities for the production or testing of MNPR-101 radiopharmaceutical program, camsirubicin, or MNPR-202, nor do we have plans to develop our own manufacturing operations in the foreseeable future.
Any information contained in, or that can be accessed through our website, is not incorporated by reference in this Annual Report on Form 10-K. Trademark Notice We have a registered trademark with the USPTO for “Validive”. All other trademarks, service marks and trade names in this Annual Report on Form 10-K are the property of their respective owners.
Any information contained in, or that can be accessed through our website, is not incorporated by reference in this Annual Report on Form 10-K. Trademark Notice All trademarks, service marks and trade names in this Annual Report on Form 10-K are the property of their respective owners.
We have also obtained U.S. and EU orphan drug status in soft tissue sarcoma with additional orphan cancer indications expected to follow. In December 2020, we announced the issuance of a U.S. patent (US 10,450,340) covering compositions of matter (2-pyrrilino camsirubicin) for a novel family of camsirubicin analogs.
We have also obtained U.S. and EU orphan drug status in soft tissue sarcoma. MNPR-202 In December 2020, we announced the issuance of a U.S. patent (US 10,450,340) covering compositions of matter (2-pyrrilino camsirubicin) for a novel family of camsirubicin analogs.
In October 2013, a Phase 1 dose escalation study conducted at the University of Iowa completed enrollment of 24 patients who received one of eight different dose levels of camsirubicin ranging from 14 to 265 mg/m 2 .
Camsirubicin Clinical Data Two clinical studies of camsirubicin have been completed and one is currently ongoing. In October 2013, a Phase 1 dose escalation study conducted at the University of Iowa completed enrollment of 24 patients who received one of eight different dose levels of camsirubicin ranging from 14 to 265 mg/m 2 .
They have worked at industry leading companies such as BioMarin Pharmaceutical Inc., Raptor Pharmaceuticals, and Onyx Pharmaceuticals. As of March 10, 2023, we had twelve employees; eleven of whom were full-time.
They have worked at industry leading companies such as BioMarin Pharmaceutical Inc., Raptor Pharmaceuticals, and Onyx Pharmaceuticals. As of March 8, 2024, we had ten employees; nine of whom were full-time.
See “Risk Factors – Risks Related to our Intellectual Property”. 20 Table of Contents MNPR-101 for Radiopharmaceutical Use In collaboration with NorthStar, we filed a provisional patent application entitled “Precision Radioimmunotherapeutic Targeting of the Urokinase Plasminogen Activator Receptor (uPAR) for Treatment of Severe COVID-19 Disease” with the USPTO on June 15, 2020.
MNPR-101 for Radiopharmaceutical Use In collaboration with NorthStar, we filed a provisional patent application entitled “Precision Radioimmunotherapeutic Targeting of the Urokinase Plasminogen Activator Receptor (uPAR) for Treatment of Severe COVID-19 Disease” with the USPTO on June 15, 2020.
There can be no assurance that we will reach any milestones. As of March 10, 2023, we had not reached any milestones and had not been required to pay XOMA Ltd. any funds under this license agreement. The first milestone payment is payable upon first dosing of a human patient in a Phase 2 clinical trial.
As of March 8, 2024, we had not reached any milestones and had not been required to pay XOMA Ltd. any funds under this license agreement. The first milestone payment is payable upon first dosing of a human patient in a Phase 2 clinical trial. Onxeo S.A.
In addition, under the Pediatric Research Equity Act (“PREA”), an NDA, BLA or a supplement thereof must contain data to assess the safety and effectiveness of the pharmaceutical product for the claimed indications in all relevant pediatric subpopulations and to support dosing and administration for each pediatric subpopulation for which the product is safe and effective.
The submission of an NDA or BLA is subject to the payment of substantial user fees; a waiver of such fees may be obtained under certain limited circumstances. 19 Table of Contents In addition, under the Pediatric Research Equity Act (“PREA”), an NDA, BLA or a supplement thereof must contain data to assess the safety and effectiveness of the pharmaceutical product for the claimed indications in all relevant pediatric subpopulations and to support dosing and administration for each pediatric subpopulation for which the product is safe and effective.
This application covers novel compositions and uses of cytotoxic radioisotopes attached to antibodies that bind to uPAR, thereby creating precision targeted radiotherapeutics, also known as uPRITs, for the treatment of severe COVID-19 and other respiratory diseases. Advanced COVID-19 patients frequently develop severe, life-threatening, pulmonary inflammation as a result of a viral induced cytokine storm.
This application covers novel compositions and uses of cytotoxic radioisotopes attached to antibodies that bind to uPAR, thereby creating precision targeted radiotherapeutics, also known as uPRITs, for the treatment of severe COVID-19 and other respiratory diseases.
A Phase 2 clinical trial for camsirubicin has been completed in patients with advanced (e.g., unresectable or metastatic) soft tissue sarcoma (“ASTS”). Average life expectancy for these patients is 12-15 months.
A previous Phase 2 clinical trial for camsirubicin dosed up to 265 mg/m 2 per cycle was completed in patients with advanced (e.g., unresectable or metastatic) soft tissue sarcoma (“ASTS”). Average life expectancy for these patients is 12-15 months.
This RIT demonstrated 98% radiochemical purity and high stability and has the potential to be a highly selective, potent treatment for a variety of cancers, severe COVID-19, and other diseases characterized by aberrant uPA receptor expression.
This RIT demonstrated 98% radiochemical purity and high stability and has the potential to be a highly selective, potent treatment for a variety of cancers, severe COVID-19, and other diseases characterized by aberrant uPAR expression. 13 Table of Contents Camsirubicin Camsirubicin (GPX-150) is covered by manufacturing process patents.
Similar to doxorubicin, the antitumor effects of camsirubicin are mediated through the stabilization of the topoisomerase II complex after a DNA strand break and DNA intercalation leading to tumor cell apoptosis (cell death).
Camsirubicin has been engineered specifically to retain the anticancer activity of doxorubicin while minimizing its toxic effects on the heart. Similar to doxorubicin, the antitumor effects of camsirubicin are mediated through the stabilization of the topoisomerase II complex after a DNA strand break and DNA intercalation leading to tumor cell apoptosis (cell death).
The pharmaceutical product candidates that we develop must be approved by the FDA before they may be legally marketed in the U.S. See “Risk Factors – Risks Related to Clinical Development and Regulatory Approval”. U.S. Pharmaceutical Product Development Process In the U.S., the FDA regulates pharmaceutical products under the Federal Food, Drug and Cosmetic Act (“FDCA”) and implementing regulations.
The pharmaceutical product candidates that we develop must be approved by the U.S. Food and Drug Administration ("FDA") and the Therapeutics Goods Administration ("TGA") before they may be legally marketed in the U.S. and Australia, respectively. See “Risk Factors – Risks Related to Clinical Development and Regulatory Approval”.
Whether or not FDA approval is obtained for a product, approval of a product must be obtained by the comparable regulatory authorities of foreign countries before clinical studies or marketing of the product can commence in those countries. The approval process varies from country to country, and the time may be longer or shorter than that required for FDA approval.
Whether or not FDA or HREC approval is obtained for a product, approval of a product must be obtained by the comparable regulatory authorities of foreign countries before clinical studies or marketing of the product can commence in those countries.
Item 1. Business You should read the following discussion in conjunction with our financial statements as of December 31, 2022, and the notes to such financial statements included elsewhere in this Annual Report on Form 10-K.
Item 1. Business You should read the following discussion in conjunction with our financial statements as of December 31, 2023, and the notes to such financial statements included elsewhere in this Annual Report on Form 10-K. Overview We are a clinical stage biopharmaceutical company focused on developing innovative treatments for cancer patients.
Some of our patents are currently near expiration and we may pursue patent term extensions for these where appropriate.
Some of our patents are currently near expiration and we may pursue patent term extensions for these where appropriate or to let patents lapse. See “Risk Factors – Risks Related to our Intellectual Property”.
The agreement will be binding on the FDA and may not be changed by the sponsor or the FDA after the trial begins except with the written agreement of the sponsor and the FDA or if the FDA determines that a substantial scientific issue essential to determining the safety or efficacy of the drug was identified after the testing began. 23 Table of Contents Clinical studies involve the administration of the pharmaceutical product candidate to healthy volunteers or patients under the supervision of qualified investigators, generally physicians not employed by or under the clinical study sponsor’s control.
The agreement will be binding on the FDA and may not be changed by the sponsor or the FDA after the trial begins except with the written agreement of the sponsor and the FDA or if the FDA determines that a substantial scientific issue essential to determining the safety or efficacy of the drug was identified after the testing began.
If resolution cannot be reached within the 30-day review period, either the FDA places the IND on clinical hold, or the sponsor withdraws the application. The FDA may also impose clinical holds on a pharmaceutical product candidate at any time before or during clinical studies due to safety concerns or non-compliance.
The FDA may also impose clinical holds on a pharmaceutical product candidate at any time before or during clinical studies due to safety concerns or non-compliance.
To humanize our MNPR-101 antibody, we have taken a non-exclusive license to XOMA (US) LLC’s humanization technology and know-how. Humanization involves replacing most of the non-critical parts of the mouse sequence of an antibody with the human sequence to minimize the ability of the human immune system to recognize this antibody as foreign.
Humanization involves replacing most of the non-critical parts of the mouse sequence of an antibody with the human sequence to minimize the ability of the human immune system to recognize this antibody as foreign. As such, MNPR-101 has been engineered to be 95% human sequence using the XOMA technology.
We presently depend on third-party contract manufacturers for all our required raw materials, Active Pharmaceutical Ingredients (“API”), and finished drug products for our preclinical and clinical studies.
We presently depend on third-party contract manufacturers for all our required raw materials, Active Pharmaceutical Ingredients (“API”), and finished drug products for our preclinical and clinical studies. We are having clinical batches of MNPR-101-Zr manufactured in preparation for treating patients in our Phase 1 radiopharma program in advanced cancers.
Doxorubicin is used to treat adult and pediatric solid and blood (hematologic) cancers, including soft tissue sarcomas, breast, gastric, ovarian and bladder cancers, leukemias and lymphomas. Despite clinical studies demonstrating the anti-cancer benefit of higher cumulative doses of doxorubicin, the clinical efficacy of doxorubicin has historically been limited by the risk of patients developing irreversible, potentially life-threatening cardiotoxicity.
Despite clinical studies demonstrating the anti-cancer benefit of higher cumulative doses of doxorubicin, the clinical efficacy of doxorubicin has historically been limited by the risk of patients developing irreversible, potentially life-threatening cardiotoxicity.
Despite some subjects in this study receiving camsirubicin for up to 20 cycles, effects on cardiac function were of no clinical significance and there was no evidence of irreversible heart failure in any subject. 15 Table of Contents Camsirubicin Preclinical Data In preclinical studies, camsirubicin showed a lack of acute as well as chronic functional cardiotoxicity and did not cause the cardiac histopathologic lesions observed with doxorubicin in a chronic rabbit model.
Despite some subjects in this study receiving camsirubicin for up to 20 cycles, effects on cardiac function were of no clinical significance and there was no evidence of irreversible heart failure in any subject.
With the cumulative dose restriction on doxorubicin, the median progression free survival for ASTS patients is approximately 6 months, with median overall survival of 12-15 months.
With the cumulative dose restriction on doxorubicin, the median progression free survival for ASTS patients is approximately 6 months, with median overall survival of 12-15 months. There is a significant unmet opportunity to develop a replacement for doxorubicin that can be dosed higher and for longer to improve anti-tumor activity.
Camsirubicin was very well tolerated in this study and underscored the ability to potentially administer camsirubicin without restriction of cumulative dose in patients with ASTS. Although doxorubicin has been the standard of care treatment for ASTS for over 40 years, doxorubicin is limited to a lifetime cumulative dose maximum of 450 mg/m 2 .
Camsirubicin was very well tolerated in this study and underscored the ability to potentially administer camsirubicin without restriction of cumulative dose in patients with ASTS.
As such, MNPR-101 has been engineered to be 95% human sequence using the XOMA technology. Under the terms of the license, we are to pay only upon developmental and sales milestone achievements which could reach up to $14.925 million if we achieve all milestones. The agreement does not require the payment of sales royalties.
Under the terms of the non-exclusive license with XOMA Ltd., we are to pay only upon clinical, regulatory and sales milestones which could reach up to $14.925 million if we achieve all milestones. The agreement does not require the payment of sales royalties. There can be no assurance that we will reach any milestones.
Intellectual Property Portfolio and Exclusivity An important part of our strategy is obtaining patent protection to help preserve the proprietary nature of our product candidates, and to prevent others from developing competitive agents that are similar. Our patent portfolio includes issued patents and pending patent applications in the U.S. and in foreign countries.
We have not incurred any license or royalty obligations and the license has been terminated effective January 2024. 12 Table of Contents Intellectual Property Portfolio and Exclusivity An important part of our strategy is obtaining patent protection to help preserve the proprietary nature of our product candidates, and to prevent others from developing competitive agents that are similar.
Preclinical tests include laboratory evaluations of product chemistry, toxicity and formulation, as well as in-vitro and animal studies to assess the potential safety and activity of the pharmaceutical product candidate. These early proof-of-principle studies are done using sound scientific procedures and thorough documentation.
Before testing any compounds with potential therapeutic value in humans, the pharmaceutical product candidate enters the preclinical testing stage. Preclinical tests include laboratory evaluations of product chemistry, toxicity and formulation, as well as in-vitro and animal studies to assess the potential safety and activity of the pharmaceutical product candidate.
The requirements governing the conduct of clinical studies, product licensing, pricing and reimbursement vary greatly from country to country.
The approval process varies from country to country, and the time may be longer or shorter than that required for FDA or HREC approval. The requirements governing the conduct of clinical studies, product licensing, pricing and reimbursement vary greatly from country to country.
We leverage our scientific and clinical experience to help reduce the risk and accelerate the clinical development of our drug product candidates.
We are building a drug candidate pipeline through in-house development as well as the licensing and acquisition of therapeutics in late preclinical and in clinical development stages. We leverage our scientific and clinical experience to help reduce the risk and accelerate the clinical development of our drug product candidates.
We have completed manufacturing of the clinical batches of drug product for Validive that are currently being utilized in our ongoing Phase 2b/3 VOICE clinical trial and for camsirubicin which are being used in our ongoing Phase 1b dose-escalation camsirubicin clinical trial. We are in the midst of manufacturing more camsirubicin for the clinical trials.
Also, we have completed manufacturing of the clinical batches of drug product for camsirubicin which are being used in our ongoing Phase 1b dose-escalation camsirubicin clinical trial. Oncology Market Competition The pharmaceutical industry in general, and the oncology therapeutics sector in particular, are characterized by intense competition.
MNPR-101 for Radiopharmaceutical Use and MNPR-202 Our MNPR-101-Zr, MNPR-101 RIT and MNPR-202 programs are in the early stages of development and the most susceptible to all of the competitive factors listed in the first paragraph of this section on Oncology Market Competition.
In addition to approved products, there are a number of product candidates in development, largely as new formulations or derivatives of doxorubicin. MNPR-202 Competition Our MNPR-202 program is in the early stages of development and as such is the most susceptible to all of the competitive factors listed in the first paragraph of this section on Oncology Market Competition.
The conduct of single and repeat dose toxicology and toxicokinetic studies in animals must comply with federal regulations and requirements including GLP. The sponsor must submit the results of the preclinical tests, together with manufacturing information, analytical data, any available clinical data or literature and a proposed clinical protocol, to the FDA as part of the IND.
The sponsor must submit the results of the preclinical tests, together with manufacturing information, analytical data, any available clinical data or literature and a proposed clinical protocol, to the FDA as part of the IND. The IND automatically becomes effective 30 days after receipt by the FDA, unless the FDA has concerns and notifies the sponsor.
The fifth dose level is over twice the highest dose reached in any prior camsirubicin clinical trial (650 mg/m 2 versus 265 mg/m 2 ) and no drug-related cardiotoxicity has been observed to date up to the current dose-level. The open-label Phase 1b camsirubicin dose-escalation trial is planning to enroll additional cohorts until the maximum tolerable dose is reached.
The fifth dose level is over twice the highest dose reached in any prior camsirubicin clinical trial (650 mg/m 2 versus 265 mg/m 2 ).
Overall, the imaging results demonstrate the potential utility of MNPR-101 as a precision targeting agent for both imaging and therapy in multiple cancer indications. MNPR-101 RIT Also pursuant to our collaboration with NorthStar, we continue to develop potential radioimmunotherapeutics (“RITs”) based on MNPR-101.
Overall, the preclinical imaging and therapeutic efficacy study results demonstrate the potential utility of MNPR-101 as a precision targeting radiopharmaceutical agent for both imaging and therapy in multiple cancer indications. We are actively working towards enrolling our Phase 1 dosimetry clinical trial in Australia for MNPR-101-Zr in patients with advanced cancer.
The IND automatically becomes effective 30 days after receipt by the FDA, unless the FDA has concerns and notifies the sponsor. In such a case, the IND sponsor and the FDA must resolve any outstanding concerns before the clinical study can begin.
In such a case, the IND sponsor and the FDA must resolve any outstanding concerns before the clinical study can begin. If resolution cannot be reached within the 30-day review period, either the FDA places the IND on clinical hold, or the sponsor withdraws the application.
Positron emission tomography (“PET”) imaging of preclinical mouse models for triple-negative breast, colorectal, and pancreatic tumors displayed high and selective uptake of MNPR-101-Zr in these uPAR-expressing tumors. These proof-of-concept studies provide support for a first-in-human PET imaging study with MNPR-101-Zr and a future therapeutic study using actinium-225 labeled radioimmunotherapeutic version of MNPR-101.
Positron emission tomography (“PET”) imaging data of preclinical human tumor xenograft mouse models for triple-negative breast, colorectal, and pancreatic tumors expressing uPAR display high, selective and durable uptake of MNPR-101 conjugated to the imaging radioisotope zirconium-89 ("MNPR-101-Zr"). Additionally, preclinical triple-negative breast and pancreatic cancer mouse model studies with MNPR-101 conjugated to therapeutic radioisotopes ("MNPR-101-RIT") have shown promising anti-tumor activity.
The agreement includes clinical, regulatory, developmental and sales milestones that could reach up to $108 million if we achieve all milestones, and escalating royalties from 5% to 10% on net sales.
The agreement included clinical, regulatory, developmental and sales milestones and escalating royalties on net sales. In September 2017, we exercised the option to license Validive from Onxeo for $1 million.
Even if a patient is responding to doxorubicin, their treatment is discontinued once this lifetime cumulative dose has been reached. 13 Table of Contents Camsirubicin is a proprietary doxorubicin analog that is selective for topoisomerase II-alpha.
Although doxorubicin has been the standard of care treatment for ASTS for over 40 years, doxorubicin is limited to a lifetime cumulative dose maximum of 450 mg/m 2 due to the risk of causing irreversible cardiotoxicity. Even if a patient is responding to doxorubicin, therefore, their treatment is discontinued once this lifetime cumulative dose has been reached.
Additional information can be found in the section entitled “Risk Factors – Risks Related to Our Business Operations and Industry.” Validive There is no effective standard of care or FDA approved preventive or therapeutic treatment for patients that develop chemoradiation-induced SOM.
Additional information can be found in the section entitled “Risk Factors – Risks Related to Our Business Operations and Industry.” 14 Table of Contents MNPR-101 Radiopharmaceutical Program Competition Our MNPR-101 radiopharmaceutical program, including MNPR-101-Zr and MNPR-101 conjugated to therapeutic radioisotopes, is susceptible to all of the competitive factors listed in the first paragraph of this section on Oncology Market Competition.
Overall, on human gingiva stimulated by SP, a concentration dependent decrease in TNF-alpha production was observed with clonidine, which was statistically significant at 3 µg/ml clonidine; see below: Clonidine Inhibits the Production of Pro-Inflammatory Cytokine Release from Oral Tissue ** = different from SP treatment alone, p Camsirubicin (5-imino-13-deoxydoxorubicin; formerly MNPR-201, GPX-150) Our second product candidate, camsirubicin, is a novel analog of doxorubicin which has been designed to reduce the cardiotoxic side effects generated by doxorubicin while retaining anti-cancer activity.
High specificity and durable uptake of MNPR-101-Lu in the tumor relative to normal tissue is readily apparent, and help explain the near complete elimination of tumors observed after a single injection of therapeutic radioisotopes bound to MNPR-101. 10 Table of Contents Camsirubicin (5-imino-13-deoxydoxorubicin; formerly MNPR-201, GPX-150) Camsirubicin is a novel analog of doxorubicin which has been designed to reduce the cardiotoxic side effects generated by doxorubicin while retaining effective anti-cancer activity.
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Overview We are a clinical stage biopharmaceutical company focused on developing proprietary therapeutics designed to extend life or improve quality of life for cancer patients. We are building a drug development pipeline through the licensing and acquisition of therapeutics in late preclinical and clinical development stages.
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We currently have several compounds in development: 1) MNPR-101-Zr, a clinical stage uPAR-targeted radiodiagnostic imaging agent; 2) MNPR-101-RIT, a late preclinical stage radiotherapeutic for advanced cancers; 3) camsirubicin (generic name for MNPR-201, GPX-150; 5-imino-13-deoxydoxorubicin), a Phase 1b clinical stage novel analog of doxorubicin engineered specifically to retain anticancer activity while minimizing toxic effects on the heart; and 4) an early stage camsirubicin analog, MNPR-202, for various cancers.
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During 2022, we expanded the number of clinical trial sites in our global Phase 2b/3 clinical trial of our lead product candidate, Validive ® (clonidine hydrochloride mucobuccal tablet; clonidine HCI MBT), for the prevention of chemoradiotherapy (“CRT”)-induced se v ere o ral mucositis (“SOM”) in pat i ents with oropharyngeal c anc e r (“VOICE” trial).
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Our Product Pipeline 7 Table of Contents Our Product Candidates MNPR-101 for Radiopharmaceutical Use Our MNPR-101 radiopharmaceutical program was developed by us for advanced cancers expressing urokinase plasminogen activator receptor ("uPAR"). This proprietary, novel first-in-class radiopharmaceutical program aims to identify and selectively kill the tumors expressing uPAR, which include a majority of triple-negative breast, colorectal, and pancreatic cancers.
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We currently have active sites in the U.S., Spain, France, Germany and Poland and have completed enrollment of the Phase 2b portion of the clinical trial with a go/no go interim analysis decision from our independent data monitoring committee anticipated by the end of March 2023.
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The program uses MNPR-101, our proprietary humanized monoclonal antibody targeting uPAR, as a means to accurately deliver radioisotope payloads to the tumors. We have demonstrated promising preclinical data to-date for our MNPR-101 radiopharmaceutical program.
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We also continued enrolling in our U.S.-based open-label, Phase 1b clinical trial of camsirubicin for the treatment of advanced soft tissue sarcoma (“ASTS”). We also, in collaboration with our partner, NorthStar Medical Radioisotopes, LLC, continue to move forward with the development of MNPR-101 for radiopharmaceutical use in advanced cancers.
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MNPR-101 is designed to selectively bind to uPAR. uPAR is highly expressed in multiple types of tumors, including breast, pancreatic, and colorectal cancers but not on most normal cells. It is estimated that the tumors and/or tumor associated cells in 97% of breast, 89% of bladder, 87% of pancreatic and 85% of colorectal cancer patients express uPAR.
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Finally, we continue to develop MNPR-202, an analog of camsirubicin designed to potentially treat doxorubicin- and camsirubicin-resistant cancers, which is being tested in preclinical models by our collaborator, the Cancer Science Institute of Singapore at the National University of Singapore.
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Moreover, several Phase 1 PET imaging studies in advanced cancer patients show that uPAR can only be detected in the tumor and not in normal tissues, making it a potentially attractive target for cancer therapies, including radiopharmaceuticals.
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To complete the VOICE clinical program, including, if required, completing a second Phase 3 confirmatory clinical trial, we will require additional funding in the millions or tens of millions of dollars (depending on if we have consummated a collaboration or partnership or neither for Validive) which we are planning to pursue within the next 12 months.
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In February 2024, we received Human Research Ethics Committee (HREC) clearance in Australia to commence our Phase 1 dosimetry trial for MNPR-101-Zr in patients with advanced cancers. The trial will utilize total body PET/CT ("positron emission tomography–computed tomography") imaging to assess tumor uptake, normal organ biodistribution, and safety.
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We also require additional funding to continue to develop camsirubicin through and beyond our ongoing Phase 1b clinical trial and to further fund our current and future product pipeline. 5 Table of Contents Our Product Pipeline Our Product Candidates Validive (clonidine hydrochloride mucobuccal tablet; clonidine HCI MBT) Validive is designed to be used prophylactically to prevent SOM in patients undergoing CRT for oropharyngeal cancer (“OPC”).
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The study will be conducted at Melbourne Theranostic Innovation Centre ("MTIC")headed by Professor Rodney Hicks, MBBS(Hons), MD, FRACP, FICIS, FAAHMS, and will use one of the world's most sensitive clinical total-body PET/CT scanners, the Siemens Biograph Vision Quadra, to image the targeting ability of MNPR-101-Zr in cancer patients.
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SOM is a painful and debilitating inflammation and ulceration of the mucous membranes lining the oral cavity and oropharynx in response to chemoradiation. The majority of patients receiving CRT to treat their OPC develop SOM, which remains one of the most common and devastating side effects of treatment in this indication.
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If the tumor uptake, biodistribution, and safety look encouraging in this Phase 1 clinical trial, which is anticipated to enroll approximately 12 patients, we plan to evaluate the efficacy in humans of a therapeutic version of MNPR-101 radiolabeled with an isotope such as actinium-225 ("Ac-225" or "Ac"). 8 Table of Contents Overview of Preclinical Development In February 2024, we announced promising preclinical data for MNPR-101 radiopharmaceutical imaging and therapeutic agents demonstrating highly selective and durable uptake in uPAR expressing tumors and potent anti-tumor effects in human tumor xenograft mouse models.
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The potential clinical benefits to preventing SOM in patients include: reduced treatment discontinuations leading to potentially improved overall survival outcomes; reduced mouth and throat pain avoiding the need for feeding tube intervention; decreased long-term and often permanent debilitation arising from swallowing difficulties, neck and throat spasms, and lung complications due to food aspiration; and decreased reliance on pain medication.
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Maximizing the dose delivered to the tumor relative to normal tissue is of paramount importance in radiopharmaceutical therapy. Figure 1 below shows the before and after optimization of MNPR-101-Zr. MNPR-101-Zr is a zirconium-89 labeled version of MNPR-101 that is being developed as a radiopharmaceutical imaging agent for advanced solid tumors expressing uPAR.
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Our mucobuccal tablet (“MBT”) formulation is a novel delivery system for clonidine that allows for prolonged and enhanced local delivery of drug in the regions of mucosal radiation damage in patients with OPC.
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Monopar’s in-house radiopharmaceutical development team was able to significantly increase tumor uptake of MNPR-101-Zr while minimizing uptake in healthy tissue, as shown in this preclinical PET sequential imaging time-series.
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Validive has been granted fast track designation in the U.S., orphan drug designation in the EU, and has global intellectual property patent protection through mid-2029 not accounting for possible patent extensions. In September 2017, we exercised an option to license Validive from Onxeo S.A., the company that developed Validive through its Phase 2 clinical trial.
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The high specificity and durable tumor uptake are evident in the After Optimization panel below. 9 Table of Contents Preclinical data to date demonstrate compelling and durable anti-tumor benefits with MNPR-101 conjugated to therapeutic radioisotopes.

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Item 1A. Risk Factors

Risk Factors — what could go wrong, per management

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Biggest changeTherefore, we will need to raise significant additional funds or find a suitable pharmaceutical partner within the next 12 months to complete the VOICE clinical program, as well as support further development of camsirubicin through and beyond our ongoing Phase 1b, to support MNPR-101-Zr, MNPR-101 RIT and MNPR-202 and related compounds in various indications and generally to support our current and any future product candidates through completion of clinical trials, approval processes and, if applicable, commercialization, If we are able to raise financing, it may be on terms that are unfavorable to us and if we are unable to raise sufficient funds or find a suitable pharmaceutical partner, we may have to discontinue or delay clinical development of Validive and/or any other of our current or future product candidates.
Biggest changeTherefore, we will need to raise significant additional funds or find a suitable pharmaceutical partner within the next 12 months to support our current and any future product candidates through completion of clinical trials, approval processes and, if applicable, commercialization.
If we are unable to successfully settle future claims on terms acceptable to us, we may be required to engage in or to continue costly, unpredictable and time-consuming litigation and may be prevented from, or experience substantial delays in, marketing our drug candidates.
If we are unable to successfully settle future claims on terms acceptable to us, we may be required to engage in or to continue costly, unpredictable and time-consuming litigation and may be prevented from, or experience substantial delays in, marketing our drug candidates.
For as long as we continue to be an emerging growth company, we also intend to take advantage of certain other exemptions from various reporting requirements that are applicable to other public companies including, but not limited to, reduced disclosure obligations regarding executive compensation in our periodic reports and proxy statements, exemptions from the requirements of holding a nonbinding advisory stockholder vote on executive compensation and any golden parachute payments not previously approved, exemption from the requirement of auditor attestation in the assessment of our internal control over financial reporting and exemption from any requirement that may be adopted by the Public Company Accounting Oversight Board regarding mandatory audit firm rotation or a supplement to the auditor’s report providing additional information about the audit and the financial statements (auditor discussion and analysis).
For as long as we continue to be an emerging growth company, we intend to take advantage of certain other exemptions from various reporting requirements that are applicable to other public companies including, but not limited to, reduced disclosure obligations regarding executive compensation in our periodic reports and proxy statements, exemptions from the requirements of holding a nonbinding advisory stockholder vote on executive compensation and any golden parachute payments not previously approved, exemption from the requirement of auditor attestation in the assessment of our internal control over financial reporting and exemption from any requirement that may be adopted by the Public Company Accounting Oversight Board regarding mandatory audit firm rotation or a supplement to the auditor’s report providing additional information about the audit and the financial statements (auditor discussion and analysis).
Examples of delays or difficulties that we may encounter in our clinical trials include without limitation the following: ● Clinical trials may not yield sufficiently conclusive results for regulatory agencies to approve the use of our products. ● Our products may fail to be more effective than current therapies, or to be effective at all. ● We may discover that our products have adverse side effects, which could cause our products to be delayed or precluded from receiving regulatory approval or reduce the effective size of our target patient population or otherwise expose us to significant commercial and legal risks. ● It may take longer than expected to determine whether or not a treatment is safe and effective. ● Patients involved in our clinical trials may suffer severe adverse side effects even up to death, whether as a result of treatment with our products, the withholding of such treatment, or other reasons which may not include the effects of our treatment (whether within or outside of our control). 34 Table of Contents ● We may fail to be able to enroll a sufficient number of patients in our clinical trials to meet trial statistical plans and gain statistical significance, or it may take longer than expected to enroll. ● Patients enrolled in our clinical trials may not have the safety or efficacy characteristics necessary to obtain regulatory approval for a particular indication or patient population. ● We may be unable to produce sufficient quantities of product to complete the clinical trials. ● Even if we are successful in our clinical trials, required governmental approvals may still not be obtained or, if obtained, may not be maintained. ● If approval for commercialization is granted, it is possible the authorized use will be more limited than is necessary for commercial success, or that approval may be conditioned on completion of further clinical trials or other activities, which will cause a substantial increase in costs and which we might not succeed in performing or completing. ● If granted, approval may be withdrawn or limited if problems with our products emerge or are suggested by the data arising from their use or if there is a change in law or regulation.
Examples of delays or difficulties that we may encounter in our clinical trials include, without limitation. the following: ● Clinical trials may not yield sufficiently conclusive results for regulatory agencies to approve the use of our products. ● Our products may fail to be more effective than current therapies, or to be effective at all. ● We may discover that our products have adverse side effects, which could cause our products to be delayed or precluded from receiving regulatory approval or reduce the effective size of our target patient population or otherwise expose us to significant commercial and legal risks. ● It may take longer than expected to determine whether or not a treatment is safe and effective. ● Patients involved in our clinical trials may suffer severe adverse side effects even up to death, whether as a result of treatment with our products, the withholding of such treatment, or other reasons which may not include the effects of our treatment (whether within or outside of our control). ● We may fail to be able to enroll a sufficient number of patients in our clinical trials to meet trial statistical plans and gain statistical significance, or it may take longer than expected to enroll. ● Patients enrolled in our clinical trials may not have the safety or efficacy characteristics necessary to obtain regulatory approval for a particular indication or patient population. ● We may be unable to produce sufficient quantities of product to complete the clinical trials. ● Even if we are successful in our clinical trials, required governmental approvals may still not be obtained or, if obtained, may not be maintained. ● If approval for commercialization is granted, it is possible the authorized use will be more limited than is necessary for commercial success, or that approval may be conditioned on completion of further clinical trials or other activities, which will cause a substantial increase in costs and which we might not succeed in performing or completing. ● If granted, approval may be withdrawn or limited if problems with our products emerge or are suggested by the data arising from their use or if there is a change in law or regulation.
Before we can begin to commercially manufacture Validive, camsirubicin, MNPR-101-Zr, MNPR-101 RIT, MNPR-202 or any other product candidate, we must obtain regulatory approval of the manufacturing facility and process. Manufacturing of drugs for clinical and commercial purposes must comply with current Good Manufacturing Practices requirements, commonly known as “cGMP.” The cGMP requirements govern quality control and documentation policies and procedures.
Before we can begin to commercially manufacture camsirubicin, MNPR-101-Zr, MNPR-101 RIT, MNPR-202 or any other product candidate, we must obtain regulatory approval of the manufacturing facility and process. Manufacturing of drugs for clinical and commercial purposes must comply with current Good Manufacturing Practices requirements, commonly known as “cGMP.” The cGMP requirements govern quality control and documentation policies and procedures.
Complying with cGMP and non-U.S. regulatory requirements will require that we expend time, money, and effort in production, recordkeeping, and quality control to ensure that the product meets applicable specifications and other requirements. We, or our contracted manufacturing facility, must also pass a pre-approval inspection prior to FDA approval.
Complying with cGMP and non-U.S. regulatory requirements will require that we expend time, money, and effort in production, recordkeeping, and quality control to ensure that the product meets applicable specifications and other requirements. We, or our contracted manufacturing facility, must also pass a pre-approval inspection prior to FDA or TGA approval.
If we are not able to raise needed funding under acceptable terms or at all, then we will have to reduce expenses, including the possible options of curtailing operations, abandoning opportunities, licensing or selling off assets, reducing costs to a point where clinical development or other progress is impaired, or ceasing operations entirely. 33 Table of Contents Market variables, such as inflation of product costs, labor rates and fuel, freight and energy costs, as well as geopolitical events could likely cause us to suffer significant increases in our operating and administrative expenses.
If we are not able to raise needed funding under acceptable terms or at all, then we will have to reduce expenses, including the possible options of curtailing operations, abandoning opportunities, licensing or selling off assets, reducing costs to a point where clinical development or other progress is impaired, or ceasing operations entirely. 25 Table of Contents Market variables, such as inflation of product costs, labor rates and fuel, freight and energy costs, as well as geopolitical events could likely cause us to suffer significant increases in our operating and administrative expenses.
To the extent that any of our product candidates are ultimately sold in a foreign country, we may be subject to similar foreign laws and regulations, which may include, for instance, applicable post-marketing requirements, including safety surveillance, anti-fraud and abuse laws, and implementation of corporate compliance programs and reporting of payments or transfers of value to healthcare professionals. 44 Table of Contents Negotiated prices for our products covered by a Part D prescription drug plan and other government programs will be lower than the prices we might otherwise obtain.
To the extent that any of our product candidates are ultimately sold in a foreign country, we may be subject to similar foreign laws and regulations, which may include, for instance, applicable post-marketing requirements, including safety surveillance, anti-fraud and abuse laws, and implementation of corporate compliance programs and reporting of payments or transfers of value to healthcare professionals. 38 Table of Contents Negotiated prices for our products covered by a Part D prescription drug plan and other government programs will be lower than the prices we might otherwise obtain.
Future legislation or executive or private sector actions related to healthcare reform could materially and adversely affect our business by reducing our ability to generate revenue at prices sufficient to reward for the risks and costs of pharmaceutical development, to raise capital, and to market our products. 56 Table of Contents There is no assurance that federal or state healthcare reform will not adversely affect our future business and financial results, and we cannot predict how future federal or state legislative, judicial or administrative changes relating to healthcare reform and third-party payers will affect the pharmaceutical industry in general and our business in particular.
Future legislation or executive or private sector actions related to healthcare reform could materially and adversely affect our business by reducing our ability to generate revenue at prices sufficient to reward for the risks and costs of pharmaceutical development, to raise capital, and to market our products. 50 Table of Contents There is no assurance that federal or state healthcare reform will not adversely affect our future business and financial results, and we cannot predict how future federal or state legislative, judicial or administrative changes relating to healthcare reform and third-party payers will affect the pharmaceutical industry in general and our business in particular.
Congress, the federal courts and the USPTO, as well as other jurisdictions around the world, the laws and regulations governing patents could change in unpredictable ways that would weaken our ability to obtain new patents or to enforce our existing patents and patents that we might obtain in the future. 47 Table of Contents Obtaining and maintaining our patent protection depends on compliance with various procedural, document submission, fee payment and other requirements imposed by governmental patent agencies, and our patent protection could be reduced or eliminated for non-compliance with these requirements.
Congress, the federal courts and the USPTO, as well as other jurisdictions around the world, the laws and regulations governing patents could change in unpredictable ways that would weaken our ability to obtain new patents or to enforce our existing patents and patents that we might obtain in the future. 41 Table of Contents Obtaining and maintaining our patent protection depends on compliance with various procedural, document submission, fee payment and other requirements imposed by governmental patent agencies, and our patent protection could be reduced or eliminated for non-compliance with these requirements.
Our business is highly dependent upon receiving approvals from various U.S. and international governmental agencies and will be severely harmed if we are not granted approval to manufacture and sell our product candidates.
Our business is highly dependent upon receiving approvals from various U.S., Australian , and international governmental agencies and will be severely harmed if we are not granted approval to manufacture and sell our product candidates.
If third-party payers do not consider our products to be cost-effective compared to other available therapies, they may not cover our products as a benefit under their plans or, if they do, the level of payment may not be sufficient to allow us to sell our products on a profitable basis sufficient for our Company to remain competitive and thrive. 43 Table of Contents Adequate third-party reimbursement may not be available to enable us to maintain price levels sufficient to realize an appropriate return on our investment in the product development of that product.
If third-party payers do not consider our products to be cost-effective compared to other available therapies, they may not cover our products as a benefit under their plans or, if they do, the level of payment may not be sufficient to allow us to sell our products on a profitable basis sufficient for our Company to remain competitive and thrive. 37 Table of Contents Adequate third-party reimbursement may not be available to enable us to maintain price levels sufficient to realize an appropriate return on our investment in the product development of that product.
As a result, if we earn net taxable income, our ability to use our pre-change net operating loss carry-forwards to offset U.S. federal taxable income will be subject to limitations, which could result in increased future tax liability to us had we not been subject to such limitations. 62 Table of Contents If securities or industry analysts do not publish research or publish inaccurate or unfavorable research about our business, our stock price and trading volume could decline.
As a result, if we earn net taxable income, our ability to use our pre-change net operating loss carry-forwards to offset U.S. federal taxable income will be subject to limitations, which could result in increased future tax liability to us had we not been subject to such limitations. 56 Table of Contents If securities or industry analysts do not publish research or publish inaccurate or unfavorable research about our business, our stock price and trading volume could decline.
Further, if this occurs, our competitors may take advantage of our investment in development and trials by referencing our clinical and preclinical data and launch their product earlier than might otherwise be the case, and our competitive position, business, financial condition, results of operations, and prospects would be materially harmed. 46 Table of Contents Intellectual property disputes could require us to spend time and money to address such disputes and could limit our intellectual property rights.
Further, if this occurs, our competitors may take advantage of our investment in development and trials by referencing our clinical and preclinical data and launch their product earlier than might otherwise be the case, and our competitive position, business, financial condition, results of operations, and prospects would be materially harmed. 40 Table of Contents Intellectual property disputes could require us to spend time and money to address such disputes and could limit our intellectual property rights.
Patent and other intellectual property rights also will not protect our drug candidates and technologies if competitors or third parties design around such drug candidates and technologies without legally infringing, misappropriating or violating our patent or other intellectual property rights. 49 Table of Contents The cost to us in defending or initiating any litigation or other proceedings relating to our patent or other intellectual property rights, even if resolved in our favor, could be substantial, and any litigation or other proceedings would divert our management’s attention and distract our personnel from their normal responsibilities.
Patent and other intellectual property rights also will not protect our drug candidates and technologies if competitors or third parties design around such drug candidates and technologies without legally infringing, misappropriating or violating our patent or other intellectual property rights. 43 Table of Contents The cost to us in defending or initiating any litigation or other proceedings relating to our patent or other intellectual property rights, even if resolved in our favor, could be substantial, and any litigation or other proceedings would divert our management’s attention and distract our personnel from their normal responsibilities.
Many of these companies, firms, and other institutions have greater financial resources than us and may be better able to withstand and respond to adverse market conditions within the biopharmaceutical industry, including without limitation the lengthy product development and regulatory approval processes for product candidates. 52 Table of Contents We face significant competition from other biotechnology and pharmaceutical companies, and our operating results will suffer if we fail to compete effectively.
Many of these companies, firms, and other institutions have greater financial resources than us and may be better able to withstand and respond to adverse market conditions within the biopharmaceutical industry, including without limitation the lengthy product development and regulatory approval processes for product candidates. 46 Table of Contents We face significant competition from other biotechnology and pharmaceutical companies, and our operating results will suffer if we fail to compete effectively.
To the extent that we enter into any marketing, sales, or distribution arrangements with third parties, our product revenues per unit sold are expected to be lower than if we marketed, sold, and distributed our products directly, and any revenues we receive will depend upon the efforts of such third parties. 42 Table of Contents If we are unable to establish such third-party marketing and sales relationships, or choose not to do so, we would have to establish in-house marketing and sales capabilities.
To the extent that we enter into any marketing, sales, or distribution arrangements with third parties, our product revenues per unit sold are expected to be lower than if we marketed, sold, and distributed our products directly, and any revenues we receive will depend upon the efforts of such third parties. 36 Table of Contents If we are unable to establish such third-party marketing and sales relationships, or choose not to do so, we would have to establish in-house marketing and sales capabilities.
This could result in continuing uncertainty regarding compliance matters and higher costs necessitated by ongoing revisions to disclosure and governance practices. 51 Table of Contents Despite ongoing compliance training and periodic education, our employees and consultants may engage in misconduct or other improper activities, including noncompliance with regulatory standards and requirements, which could result in delays or terminations of our development programs and adversely affect our business.
This could result in continuing uncertainty regarding compliance matters and higher costs necessitated by ongoing revisions to disclosure and governance practices. 45 Table of Contents Despite ongoing compliance training and periodic education, our employees and consultants may engage in misconduct or other improper activities, including noncompliance with regulatory standards and requirements, which could result in delays or terminations of our development programs and adversely affect our business.
As a public company, and particularly after we are no longer an emerging growth company, we will incur significant legal, accounting and other expenses that we did not incur as a private company.
As a public company, and particularly after we are no longer an emerging growth company after 2024, we will incur significant legal, accounting and other expenses that we did not incur as a private company.
The estimated required capital and time-frames necessary to achieve these developmental milestones as described in this Annual Report on Form 10-K or as we may state from time to time is subject to inherent risks, which are beyond our control. Clinical development of Validive, camsirubicin, MNPR-101-Zr, MNPR-101 RIT, and MNPR-202 will require significant funds.
The estimated required capital and time-frames necessary to achieve these developmental milestones as described in this Annual Report on Form 10-K or as we may state from time to time are subject to inherent risks, which are beyond our control. Clinical development of MNPR-101-Zr, MNPR-101 RIT, camsirubicin and MNPR-202 will require significant funds.
Any of these factors could harm our ongoing international clinical operations and supply chain, as well as any future international expansion and operations and, consequently, our business, financial condition, prospects and results of operations. 59 Table of Contents We are subject to U.S. and foreign anti-corruption and anti-money laundering laws with respect to our operations and non-compliance with such laws can subject us to criminal or civil liability and harm our business.
Any of these factors could harm our ongoing international clinical operations and supply chain, as well as any future international expansion and operations and, consequently, our business, financial condition, prospects and results of operations. 53 Table of Contents We are subject to U.S. and foreign anti-corruption and anti-money laundering laws with respect to our operations and non-compliance with such laws can subject us to criminal or civil liability and harm our business.
Risks Related to Our Financial Condition and Capital Requirements We have a limited operating history, expect to incur significant operating losses, and have a high risk of never being profitable. We commenced operations in December 2014 and have an operating history of approximately eight years. Therefore, there is limited historical financial or operational information upon which to evaluate our performance.
Risks Related to Our Financial Condition and Capital Requirements We have a limited operating history, expect to incur significant operating losses, and have a high risk of never being profitable. We commenced operations in December 2014 and have an operating history of approximately nine years. Therefore, there is limited historical financial or operational information upon which to evaluate our performance.
Our lack of experience in these critical areas makes it difficult for a prospective investor to evaluate our abilities and increases the risk that we will fail to successfully execute our strategies. 50 Table of Contents Furthermore, if our business grows rapidly, our operational, managerial, legal, and financial resources will be strained.
Our lack of experience in these critical areas makes it difficult for a prospective investor to evaluate our abilities and increases the risk that we will fail to successfully execute our strategies. 44 Table of Contents Furthermore, if our business grows rapidly, our operational, managerial, legal, and financial resources will be strained.
Moreover, the FDA, EMA and other foreign regulatory authorities require us to comply with regulations and standards, including some regulations commonly referred to as good clinical practices (“GCPs”), for conducting, monitoring, recording and reporting the results of clinical trials to ensure that the data and results are scientifically credible and accurate, and that the trial subjects are adequately informed of the potential risks of participating in clinical trials. 41 Table of Contents In addition, the execution of non-clinical studies and clinical trials, and the subsequent compilation and analyses of the data produced, requires coordination among various parties.
Moreover, the FDA, TGA, EMA and other foreign regulatory authorities require us to comply with regulations and standards, including some regulations commonly referred to as good clinical practices (“GCPs”), for conducting, monitoring, recording and reporting the results of clinical trials to ensure that the data and results are scientifically credible and accurate, and that the trial subjects are adequately informed of the potential risks of participating in clinical trials. 35 Table of Contents In addition, the execution of non-clinical studies and clinical trials, and the subsequent compilation and analyses of the data produced, requires coordination among various parties.
In the wake of the COVID-19 pandemic, the Russia-Ukraine war and other geopolitical factors, economic conditions have become strained, with inflation and supply chain challenges impacting businesses worldwide. These conditions affect fuel costs and shipping, resulting in higher costs and delays for various types of supplies.
In the wake of the COVID-19 pandemic, the Russia-Ukraine war, the Israel-Hamas war and other geopolitical factors, economic conditions have become strained, with inflation and supply chain challenges impacting businesses worldwide. These conditions affect fuel costs and shipping, resulting in higher costs and delays for various types of supplies.
From time to time, global and domestic credit and financial markets have experienced extreme disruptions, including severely diminished liquidity and credit availability, declines in consumer confidence, declines in economic growth, increases in unemployment rates, and uncertainty about economic stability. Recently, COVID-19 and the Russia-Ukraine war have created volatility and uncertainty.
From time to time, global and domestic credit and financial markets have experienced extreme disruptions, including severely diminished liquidity and credit availability, declines in consumer confidence, declines in economic growth, increases in unemployment rates, and uncertainty about economic stability. Recently, COVID-19, the Russia-Ukraine war and the Israel-Hamas war have created volatility and uncertainty.
See “Cautionary Statement Concerning Forward-Looking Statements.” 58 Table of Contents Our present and potential future international operations may expose us to business, political, operational, and financial risks associated with doing business outside of the U.S. Our business is subject to risks associated with conducting business internationally.
See “Cautionary Statement Concerning Forward-Looking Statements.” 52 Table of Contents Our present and potential future international operations may expose us to business, political, operational, and financial risks associated with doing business outside of the U.S. Our business is subject to risks associated with conducting business internationally.
Accordingly, although there can be no assurance that we will undertake or successfully complete any transactions of the nature described above, any transactions that we do complete may be subject to the foregoing or other risks, and could have a material adverse effect on our business, results of operations, financial condition and prospects. 53 Table of Contents Our business and operations are vulnerable to computer system failures, cyber-attacks or deficiencies in our cyber-security, which could increase our expenses, divert the attention of our management and key personnel away from our business operations and adversely affect our results of operations.
Accordingly, although there can be no assurance that we will undertake or successfully complete any transactions of the nature described above, any transactions that we do complete may be subject to the foregoing or other risks, and could have a material adverse effect on our business, results of operations, financial condition and prospects. 47 Table of Contents Our business and operations are vulnerable to computer system failures, cyber-attacks or deficiencies in our cybersecurity, which could increase our expenses, divert the attention of our management and key personnel away from our business operations and adversely affect our results of operations.
Risks Related to Our Intellectual Property If we and our third-party licensors do not obtain and preserve protection for our respective intellectual property rights, our competitors may be able to take advantage of our (and our licensors’) development efforts to develop competing drugs.
Risks Related to Our Intellectual Property If we and our third-party licensors do not obtain and preserve protection for our respective intellectual property rights, our competitors may be able to take advantage of our (and our licensors ’ ) development efforts to develop competing drugs.
Regardless of their merit or eventual outcome, product liability claims may result in: 39 Table of Contents ● withdrawal of clinical trial volunteers; ● decreased demand for our products when approved; ● injury to our reputation and significant, adverse media attention; and ● potentially significant litigation costs, including without limitation, any damages awarded to the plaintiffs if we lose or settle claims.
Regardless of their merit or eventual outcome, product liability claims may result in: ● withdrawal of clinical trial volunteers; ● decreased demand for our products when approved; ● injury to our reputation and significant, adverse media attention; and ● potentially significant litigation costs, including without limitation, any damages awarded to the plaintiffs if we lose or settle claims.
In order for us to commercialize any treatment for chemoradiation-induced SOM, cancer or any other disease indication, we must obtain regulatory approvals of such treatment for that indication. Satisfying regulatory requirements is an expensive process that takes many years and involves compliance with requirements covering research and development, testing, manufacturing, quality control, labeling and promotion of drugs for human use.
In order for us to commercialize any treatment for cancer or any other disease indication, we must obtain regulatory approvals of such treatment for that indication. Satisfying regulatory requirements is an expensive process that takes many years and involves compliance with requirements covering research and development, testing, manufacturing, quality control, labeling and promotion of drugs for human use.
The Russia-Ukraine war will likely have continuing global effects on fuel costs and shipping and broader impacts on economic, trade and financial market conditions, which could delay the shipping of supplies for our clinical material manufacturing, potentially resulting in increased manufacturing expenses, delays to our clinical programs and adverse effects on our financing activities and financial condition.
The Russia-Ukraine war and/or the Israel-Hamas war will likely have continuing global effects on fuel costs and shipping and broader impacts on economic, trade and financial market conditions, which could delay the shipping of supplies for our clinical material manufacturing, potentially resulting in increased manufacturing expenses, delays to our clinical programs and adverse effects on our financing activities and financial condition.
As a company, we have no experience in successfully obtaining regulatory approval for a product and thus may be poorly equipped to gauge, and may prove unable to manage, risks relating to obtaining such approval. Outside the U.S., our ability to market a product is contingent upon receiving clearances from appropriate non-U.S. regulatory authorities.
As a company, we have no experience in successfully obtaining regulatory approval for a product and thus may be poorly equipped to gauge, and may prove unable to manage, risks relating to obtaining such approval. Outside the U.S., our ability to market a product is contingent upon receiving clearances from appropriate non-U.S. regulatory authorities, including the HREC in Australia.
To date, we have engaged exclusively in acquiring pharmaceutical product candidates, licensing rights to product candidates, entering into collaboration agreements with respect to key services or technologies for our drug product development, and commenced clinical trials, but have not yet completed any clinical trials, received any governmental approvals, brought any product to market, manufactured products in commercial quantities or sold any pharmaceutical products.
To date, we have engaged exclusively in acquiring pharmaceutical product candidates, licensing rights to product candidates, entering into collaboration agreements with respect to key services or technologies for our drug product development, and conducted clinical trials, but have not yet received any governmental approvals, brought any product to market, manufactured products in commercial quantities or sold any pharmaceutical products.
Our anticipated operating expenses and capital expenditures over the next year are based upon our management’s estimates of possible future events. Actual amounts and the cost of new conditions could differ materially from those estimated by our management. Development of pharmaceuticals and cancer drugs is extremely risky and unpredictable.
Our anticipated operating expenses and capital expenditures over the next year are based upon our management ’ s estimates of possible future events. Actual amounts and the cost of new conditions could differ materially from those estimated by our management. Development of pharmaceuticals and cancer drugs is extremely risky and unpredictable.
In addition, because we are incorporated in Delaware, we are governed by the provisions of Section 203 of the Delaware General Corporation Law, which generally prohibits a Delaware corporation from engaging in any of a broad range of business combinations with any “interested” stockholder for a period of three years following the date on which the stockholder became an “interested” stockholder.
In addition, because we are incorporated in Delaware, we are governed by the provisions of Section 203 of the Delaware General Corporation Law, which generally prohibits a Delaware corporation from engaging in any of a broad range of business combinations with any “interested” stockholder for a period of three years following the date on which the stockholder became an “interested” stockholder. 57 Table of Contents
Additional federal, state and local laws and regulations affecting our operations may be adopted in the future. We may incur substantial costs to comply with, and substantial fines or penalties if we violate, any of these laws or regulations. We have limited the liability of and indemnified our directors and officers.
Additional federal, state and local laws and regulations affecting our operations may be adopted in the future. We may incur substantial costs to comply with, and substantial fines or penalties if we violate, any of these laws or regulations. 49 Table of Contents We have limited the liability of and indemnified our directors and officers.
However, the FDA and other regulatory organizations will learn from their total experience in the review of multiple drugs in multiple indications and they will apply the knowledge of broad and diverse experience even if less than a perfect match with our product.
However, the FDA and other regulatory organizations, including the TGA, will learn from their total experience in the review of multiple drugs in multiple indications and they will apply that knowledge of broad and diverse experience even if less than a perfect match with our product.
While we believe we have significant competitive advantages with our expertise in small molecules and biologics, and rare disease clinical development, along with a strong intellectual property portfolio, we currently face and will continue to face competition for our drug development programs from companies that target SOM, are developing doxorubicin analogs/replacement, or are targeting uPAR.
While we believe we have significant competitive advantages with our expertise in small molecules and biologics, and rare disease clinical development, along with a strong intellectual property portfolio, we currently face and will continue to face competition for our drug development programs from companies that are developing doxorubicin analogs/replacements, or are targeting uPAR.
If we, our contract research organizations (“CROs”) or our IT vendors experience security or data privacy breaches or other unauthorized or improper access to, use of, or destruction of personal data, we may face costs, significant liabilities, harm to our brand and business disruption.
If we, our contract research organizations ( “ CROs ” ) or our IT vendors experience security or data privacy breaches or other unauthorized or improper access to, use of, or destruction of personal data, we may face costs, significant liabilities, harm to our brand and business disruption.
We may become involved in securities class action litigation that could divert management’s attention and harm our business. The stock markets have from time-to-time experienced significant price and volume fluctuations that have affected the market prices for the common stock of biotechnology and pharmaceutical companies. Our stock price has experienced such fluctuations since our initial public offering.
We may become involved in securities class action litigation that could divert management ’ s attention and harm our business. The stock markets have from time-to-time experienced significant price and volume fluctuations that have affected the market prices for the common stock of biotechnology and pharmaceutical companies. Our stock price has experienced such fluctuations since our initial public offering.
To date, we have funded our operations through net proceeds from the initial public offering of our common stock, net proceeds from sales of our common stock through an at-the-market sales program, private placements of our preferred and common stock, and the net receipt of funds related to our acquisition of camsirubicin and related assets.
To date, we have funded our operations through net proceeds from the initial public offering of our common stock, net proceeds from sales of our common stock through at-the-market sales programs, private placements of our preferred and common stock, and the net receipt of funds related to our acquisition of camsirubicin and related assets.
As a result of COVID-19, we may experience further disruptions that could severely impact our business, preclinical studies and clinical trials, including: ● Delays in receiving approval from the FDA and foreign regulatory authorities to initiate our planned clinical trials; ● Delays or difficulties in enrolling and monitoring patients in our clinical trials; ● Delays or difficulties in clinical site initiation, including difficulties in recruiting clinical site investigators and clinical site staff; ● Delays in trial drug shipments due to COVID-19 vaccine shipments tying up available pharmaceutical product shipping lanes and increasing their cost; 31 Table of Contents ● Diversion of healthcare resources away from the conduct of clinical trials, including the diversion of hospitals serving as our clinical trial sites and hospital staff supporting the conduct of our clinical trials; ● Risk that participants enrolled in our clinical trials will acquire COVID-19 while the clinical trial is ongoing, which could impact the results of the clinical trial, including by increasing the number of observed adverse events; ● Interruption of key clinical trial activities, such as clinical trial site data monitoring, due to limitations on travel imposed or recommended by federal or state governments, employers and others or interruption of clinical trial subject visits and study procedures, which may impact the integrity of subject data and clinical study endpoints; ● Interruption or delays in the operations of the FDA and foreign regulatory agencies, which may impact approval timelines; ● Interruption of, or delays in receiving, supplies of our product candidates from our contract manufacturing organizations due to staffing or supply shortages, production slowdowns, global shipping delays or stoppages and disruptions in delivery systems; ● Limitation on employee resources that would otherwise be focused on the conduct of our preclinical studies and clinical trials, including because of sickness of our employees or their families or the desire of employees to avoid contact with large groups of people. ● Refusal of the FDA to accept data from clinical trials in affected geographies; and ● Impacts from prolonged remote work arrangements, such as increased cybersecurity risks.
If there is a resurgence of COVID-19 or any future pandemics arise, we may experience disruptions that could severely impact our business, preclinical studies and clinical trials, including: ● Delays in receiving approval from the FDA, the TGA in Australia and other foreign regulatory authorities to initiate our planned clinical trials; ● Delays or difficulties in enrolling and monitoring patients in our clinical trials; ● Delays or difficulties in clinical site initiation, including difficulties in recruiting clinical site investigators and clinical site staff; ● Delays in trial drug shipments due to vaccine shipments tying up available pharmaceutical product shipping lanes and increasing their cost; ● Diversion of healthcare resources away from the conduct of clinical trials, including the diversion of hospitals serving as our clinical trial sites and hospital staff supporting the conduct of our clinical trials; ● Risk that participants enrolled in our clinical trials will acquire diseases while the clinical trial is ongoing, which could impact the results of the clinical trial, including by increasing the number of observed adverse events; 26 Table of Contents ● Interruption of key clinical trial activities, such as clinical trial site data monitoring, due to limitations on travel imposed or recommended by federal or state governments, employers and others or interruption of clinical trial subject visits and study procedures, which may impact the integrity of subject data and clinical study endpoints; ● Interruption or delays in the operations of the FDA, the TGA, and other foreign regulatory agencies, which may impact approval timelines; ● Interruption of, or delays in receiving, supplies of our product candidates from our contract manufacturing organizations due to staffing or supply shortages, production slowdowns, global shipping delays or stoppages and disruptions in delivery systems; ● Limitation on employee resources that would otherwise be focused on the conduct of our preclinical studies and clinical trials, including because of sickness of our employees or their families or the desire of employees to avoid contact with large groups of people. ● Refusal of the FDA, the TGA, and other foreign regulatory authorities to accept data from clinical trials in affected geographies; and ● Impacts from prolonged remote work arrangements, such as increased cybersecurity risks.
Stockholder approval requires the consent and approval of holders of a majority or more of our outstanding stock. Shares of stock do not have cumulative voting rights and therefore, holders of a majority of the shares of our outstanding stock will be able to elect all Board members. TacticGem, LLC (“TacticGem”) owns 7,166,667 shares of common stock (54.34%).
Stockholder approval requires the consent and approval of holders of a majority or more of our outstanding stock. Shares of stock do not have cumulative voting rights and therefore, holders of a majority of the shares of our outstanding stock will be able to elect all Board members. TacticGem, LLC (“TacticGem”) owns 7,166,667 shares of common stock (41.06%).
Our contracted camsirubicin active pharmaceutical ingredient manufacturing plant and our contracted raw materials manufacturing plant are in countries in Asia and Europe, either of which may be affected by imposed tariffs and regional geopolitical factors outside of their control, including the Russia-Ukraine war, which may affect the supply of camsirubicin active pharmaceutical ingredient and raw materials.
Our contracted camsirubicin active pharmaceutical ingredient manufacturing plant as well as our contracted raw materials manufacturing plant are in countries in Asia and Europe, either of which may be affected by imposed tariffs and regional geopolitical factors outside of their control, including the Russia-Ukraine war and Israel-Hamas war, which may affect the supply of camsirubicin active pharmaceutical ingredient and raw materials.
A termination of the license agreement might force us to cease developing and/or selling MNPR-101-Zr or MNPR-101 RIT, if it gets to market. 40 Table of Contents Data provided by collaborators and other parties upon which we rely have not been independently verified and could turn out to be inaccurate, misleading, or incomplete.
A termination of the license agreement might force us to cease developing and/or selling MNPR-101-Zr or MNPR-101 RIT, if either gets to market. Data provided by collaborators and other parties upon which we rely have not been independently verified and could turn out to be inaccurate, misleading, or incomplete.
The market price of our common stock is likely to remain highly volatile and may fluctuate substantially due to many factors, including: ● announcements concerning the progress and success of our clinical trials, our ability to obtain regulatory approval for and commercialize our product candidates, including any requests we receive from the FDA for additional studies or data that result in delays in obtaining regulatory approval or launching our product candidates, if approved; ● unstable market conditions in the pharmaceutical and biotechnology sectors or the economy as a whole; ● price and volume fluctuations in the overall stock market; ● the failure of our product candidates, if approved, to achieve anticipated commercial success; in the time projected by securities analysts and others; ● announcements of the clinical success, NDA approval or introduction of new products by us or our direct competitors; ● announcements of developments concerning product development results or intellectual property rights of others; ● litigation or public concern about the safety and/or efficacy of our potential or approved products; ● actual fluctuations in our quarterly or annual operating results, and concerns by investors that such fluctuations may occur in the future and are indicative of internal problems; ● deviations in our operating results from the estimates of securities analysts or other analyst comments; 61 Table of Contents ● additions or departures of key personnel; ● healthcare reform legislation, including measures directed at controlling the pricing of pharmaceutical products, and third-party coverage and reimbursement policies; ● announcements or publicity concerning current or future strategic collaborations; ● discussion of our Company, our stock price or our potential future market value by the financial and scientific press and online investor communities; and ● market responses to the fluctuating conditions of COVID-19 or to the Russia-Ukraine war.
The market price of our common stock is likely to remain highly volatile and may fluctuate substantially due to many factors, including: ● announcements concerning the progress and success of our clinical trials, our ability to obtain regulatory approval for and commercialize our product candidates, including any requests we receive from the FDA or TGA for additional studies or data that result in delays in obtaining regulatory approval or launching our product candidates, if approved; ● unstable market conditions in the pharmaceutical and biotechnology sectors or the economy as a whole; ● price and volume fluctuations in the overall stock market; ● the failure of our product candidates, if approved, to achieve anticipated commercial success; in the time projected by securities analysts and others; ● announcements of disruptions in supply and manufacturing of radioisotopes or raw materials required to manufacture radioisotopes, and any events that may disrupt the timely supply of radiopharmaceuticals to clinical sites; ● announcements of the clinical success, NDA approval or introduction of new products by us or our direct competitors; ● announcements of developments concerning product development results or intellectual property rights of others; ● litigation or public concern about the safety and/or efficacy of our potential or approved products; 55 Table of Contents ● actual fluctuations in our quarterly or annual operating results, and concerns by investors that such fluctuations may occur in the future and are indicative of internal problems; ● deviations in our operating results from the estimates of securities analysts or other analyst comments; ● additions or departures of key personnel; ● healthcare reform legislation, including measures directed at controlling the pricing of pharmaceutical products, and third-party coverage and reimbursement policies; ● announcements or publicity concerning current or future strategic collaborations; ● discussion of our Company, our stock price or our potential future market value by the financial and scientific press and online investor communities; and ● market responses to the fluctuating conditions of COVID-19 or any future pandemics or to the Russia-Ukraine war or Israel-Hamas war.
Consequently, we have no historical basis as a company by which one can evaluate or predict reliably our future success or viability. 35 Table of Contents Additionally, while our team has experience at prior companies with regulatory filings, as a company, we have limited experience with regulatory filings with agencies such as the FDA or EMA.
Consequently, we have no historical basis as a company by which one can evaluate or predict reliably our future success or viability. Additionally, while our team has experience at prior companies with regulatory filings, as a company, we have limited experience with regulatory filings with agencies such as the FDA, TGA, or EMA.
The extent to which the long-term effects of COVID-19 further impacts our business, including our preclinical studies and clinical trials, results of operations and financial condition will depend on future developments which remain highly uncertain and cannot be predicted with confidence.
The extent to which the long-term effects of COVID-19 or any future pandemics further impact our business, including our preclinical studies and clinical trials, results of operations and financial condition will depend on future developments which remain highly uncertain and cannot be predicted with confidence.
Patient enrollment may also be affected by other factors, including: ● delays in U.S. or foreign regulatory approvals to start the clinical trial; ● coordination with clinical research organizations to enroll and administer the clinical trials; ● coordination and recruitment of collaborators and investigators at individual sites; ● size of the patient population and the effectiveness of the process for identifying patients; ● design of the clinical trial protocol; ● eligibility and exclusion criteria; ● perceived therapeutic risks and benefits of the product candidates under study; ● availability of competing commercially available therapies and other competing products’ clinical trials; ● time of year in which the trials are initiated or conducted; ● severity and prognosis of the diseases under investigation; ● ability to obtain and maintain subject consents; ● ability to enroll and treat patients in a timely manner; ● risk that enrolled subjects will drop out before completion of the trials; ● proximity and availability of clinical trial sites for prospective patients; ● ability to monitor subjects adequately during and after treatment; ● patient referral practices of physicians; and ● potential long-term effects of COVID-19. 38 Table of Contents Our inability to enroll a sufficient number of patients for clinical trials would result in significant delays and could require us to abandon one or more clinical trials altogether.
Patient enrollment may also be affected by other factors, including: ● delays in U.S., Australian or other foreign regulatory approvals to start the clinical trial; ● coordination with any clinical research organizations to enroll and administer the clinical trials; ● coordination and recruitment of collaborators and investigators at individual sites; ● size of the patient population and the effectiveness of the process for identifying patients; ● design of the clinical trial protocol; ● eligibility and exclusion criteria; ● perceived therapeutic risks and benefits of the product candidates being studied; ● availability of competing commercially available therapies and other competing products’ clinical trials; ● time of year in which the trials are initiated or conducted; ● severity and prognosis of the diseases under investigation; ● ability to obtain and maintain subject consents; ● ability to enroll and treat patients in a timely manner; ● risk that enrolled subjects will drop out before completion of the trials; ● proximity and availability of clinical trial sites for prospective patients; ● ability to monitor subjects adequately during and after treatment; ● logistical challenges posed by the time-limited shelf-life of our current or future drug candidates; ● patient referral practices of physicians; and ● potential long-term effects of COVID-19, any resurgences thereof or any future pandemics. 32 Table of Contents Our inability to enroll a sufficient number of patients for clinical trials would result in significant delays and could require us to abandon one or more clinical trials altogether.
We will need to raise additional capital in the future; the amount of additional capital needed will vary as a result of a number of factors, including without limitation the following: ● receiving less funding than we require; ● higher than expected costs to manufacture and ship our active pharmaceutical ingredient and our product candidates; ● higher than expected costs for preclinical testing; ● an increase in the number, size, duration, and/or complexity of our clinical trials; ● slower than expected progress in developing Validive, camsirubicin, MNPR-101-Zr, MNPR-101 RIT, MNPR-202 or other product candidates, including without limitation, additional costs caused by program delays; ● higher than expected costs associated with attempting to obtain regulatory approvals, including without limitation additional costs caused by additional regulatory requirements or larger clinical trial requirements; ● higher than expected personnel, consulting or other costs, such as adding personnel or industry expert consultants or pursuing the licensing/acquisition of additional assets; and ● higher than expected costs to protect our intellectual property portfolio or otherwise pursue our intellectual property strategy.
We will need to raise additional capital in the future; the amount of additional capital needed will vary as a result of a number of factors, including without limitation the following: ● receiving less funding than we require; ● higher than expected costs to manufacture and ship our active pharmaceutical ingredient, radioisotopes, and our product candidates; ● higher than expected costs for preclinical testing; ● the cost and availability of radioisotopes such as Ac-225 or Zr-89, or any other medical isotope we may incorporate into our product candidates; ● an increase in the number, size, duration, and/or complexity of our clinical trials; ● slower than expected progress in developing our MNPR-101 radiopharmaceutical program, camsirubicin, and MNPR-202 or other product candidates, including without limitation, additional costs caused by program delays; ● higher than expected costs associated with attempting to obtain regulatory approvals, including without limitation additional costs caused by additional regulatory requirements or larger clinical trial requirements; ● higher than expected personnel, consulting or other costs, such as adding personnel or industry expert consultants or pursuing the licensing/acquisition of additional assets; and ● higher than expected costs to protect our intellectual property portfolio or otherwise pursue our intellectual property strategy.
If we are unsuccessful at some or all of these undertakings, our business, financial condition, and results of operations are expected to be materially and adversely affected. 30 Table of Contents We will need to raise substantial additional funding or find a suitable pharmaceutical partner to continue to advance our clinical programs and support our preclinical activities.
If we are unsuccessful at some or all of these undertakings, our business, financial condition, and results of operations are expected to be materially and adversely affected. 23 Table of Contents We will need to raise substantial additional funding or find one or more suitable pharmaceutical partners to continue to advance our clinical programs and support our preclinical activities.
From inception in December 2014 through December 31, 2022, we have incurred losses of approximately $51.8 million, which includes $13.5 million of non-cash in-process research and development, which was incurred in connection with our 2017 acquisition of camsirubicin.
From inception in December 2014 through December 31, 2023, we have incurred losses of approximately $60.2 million, which includes $13.5 million of non-cash in-process research and development, which was incurred in connection with our 2017 acquisition of camsirubicin.
These shares are able to be sold freely in the public market upon issuance, subject to existing internal practices which prohibit sales under certain circumstances.
These shares are able to be sold freely in the public market upon issuance, subject to existing internal practices which prohibit sales under certain circumstances and volume limitations for affiliates.
In order to be commercially viable, we must successfully research, develop, test, obtain regulatory approval for, manufacture, introduce, market and distribute Validive, camsirubicin, MNPR-101-Zr, MNPR-101 RIT, MNPR-202, and, if applicable, any current and future product candidates we may develop.
In order to be commercially viable, we must successfully research, develop, test, obtain regulatory approval for, manufacture, introduce, market and distribute some or all MNPR-101-Zr, MNPR-101 RIT, camsirubicin, and MNPR-202, and, if applicable, any other product candidates we may develop.
The issuance of such equity upon vesting of restricted stock units and/or the exercise of such options will dilute both our existing and our new investors. As of March 10, 2023, 189,346 stock options have been exercised.
The issuance of such equity upon vesting of restricted stock units and/or the exercise of such options, and the grant of new equity awards, will dilute both our existing and our new investors. As of March 8, 2024, 189,346 stock options have been exercised.
In addition, any capital obtained by us may be obtained on terms that are unfavorable to us, our investors, or both. 32 Table of Contents While we believe adequate cash is currently available to operate for the next twelve months, developing a new drug and conducting clinical trials and the regulatory review processes for one or more disease indications involves substantial costs.
In addition, any capital obtained by us may be obtained on terms that are unfavorable to us, our investors, or both. 24 Table of Contents While we believe adequate cash is currently available to operate at least through June 30, 2025, developing a new drug and conducting clinical trials and the regulatory review processes for one or more disease indications involves substantial costs.
If we elect to or are forced to suspend or terminate any clinical trial with one of our product candidates, the commercial prospects of such product candidate will be harmed, and our ability to generate revenue from such product candidate will be delayed or eliminated.
If we elect to or are forced to suspend or terminate any clinical trial with one of our product candidates, the commercial prospects of such product candidate will be harmed, and our ability to generate revenue from such product candidate will be delayed or eliminated. Any of these occurrences may harm our business, financial condition and prospects significantly.
In addition, changes in the law and legal decisions by courts in the U.S. and foreign countries may affect our ability to obtain and enforce adequate intellectual property protection for our products and technology.
Accordingly, our efforts to protect our intellectual property rights in such countries may be inadequate. In addition, changes in the law and legal decisions by courts in the U.S. and foreign countries may affect our ability to obtain and enforce adequate intellectual property protection for our products and technology.
We or any of our future licensors or strategic partners, may be party to, or be threatened with, adversarial proceedings or litigation regarding intellectual property rights with respect to our current or any potential future drug candidates and technologies, including derivation, reexamination, inter partes review, post-grant review or interference proceedings before the USPTO and similar proceedings in jurisdictions outside of the U.S. such as opposition proceedings.
The biotechnology and pharmaceutical industries are characterized by extensive and complex litigation regarding patents and other intellectual property rights. 42 Table of Contents We or any of our future licensors or strategic partners, may be party to, or be threatened with, adversarial proceedings or litigation regarding intellectual property rights with respect to our current or any potential future drug candidates and technologies, including derivation, reexamination, inter partes review, post-grant review or interference proceedings before the USPTO and similar proceedings in jurisdictions outside of the U.S. such as opposition proceedings.
As a result, we anticipate that we will seek to raise additional capital within the next 12 months to fund our future operations. We will seek to obtain needed capital through a combination of equity offerings, including the usage of our Capital on Demand TM Sales Agreement with JonesTrading, debt financings, strategic collaborations and grant funding.
As a result, we anticipate that we will seek to raise additional capital within the next 12 months to fund our future operations. We will seek to obtain needed capital through a combination of equity offerings, including at-the-market sales programs, debt financings, strategic collaborations and grant funding.
Furthermore, while we intend to protect our intellectual property rights in our expected significant markets, we cannot ensure that we will be able to initiate or maintain similar efforts in all jurisdictions in which we may wish to market Validive or any future products. Accordingly, our efforts to protect our intellectual property rights in such countries may be inadequate.
Furthermore, while we intend to protect our intellectual property rights in our expected significant markets, we cannot ensure that we will be able to initiate or maintain similar efforts in all jurisdictions in which we may wish to market our current or any future product candidates.
Delaware law allows indemnification of our non-employee directors and officer, if they (a) have acted in good faith, in a manner the non-employee director or officer reasonably believes to be in or not opposed to our best interests, and (b) with respect to any criminal action or proceeding, if the non-employee director or officer had no reasonable cause to believe the conduct was unlawful. 55 Table of Contents Pursuant to the Certificate of Incorporation and indemnification agreement, each non-employee director and officer who is made a party to a legal proceeding because he or she is or was a non-employee director or officer, is indemnified by us from and against any and all liability, except that we may not indemnify a non-employee director or officer: (a) for any liability incurred in a proceeding in which such person is adjudged liable to Monopar or is subjected to injunctive relief in favor of Monopar; (b) for acts or omissions that involve intentional misconduct or a knowing violation of law, fraud or gross negligence; (c) for unlawful distributions; (d) for any transaction for which such non-employee director or officer received a personal benefit or as otherwise prohibited by or as may be disallowed under Delaware law; or (e) with respect to any dispute or proceeding between us and such non-employee director or officer unless such indemnification has been approved by a disinterested majority of the Board or by a majority in interest of disinterested stockholders.
Pursuant to the Certificate of Incorporation and indemnification agreement, each non-employee director and officer who is made a party to a legal proceeding because he or she is or was a non-employee director or officer, is indemnified by us from and against any and all liability, except that we may not indemnify a non-employee director or officer: (a) for any liability incurred in a proceeding in which such person is adjudged liable to Monopar or is subjected to injunctive relief in favor of Monopar; (b) for acts or omissions that involve intentional misconduct or a knowing violation of law, fraud or gross negligence; (c) for unlawful distributions; (d) for any transaction for which such non-employee director or officer received a personal benefit or as otherwise prohibited by or as may be disallowed under Delaware law; or (e) with respect to any dispute or proceeding between us and such non-employee director or officer unless such indemnification has been approved by a disinterested majority of the Board or by a majority in interest of disinterested stockholders.
Completion of our clinical trials and commercialization of our product candidates require access to, or development of, facilities to manufacture a sufficient supply of our product candidates. We will utilize third parties to manufacture Validive, camsirubicin, and MNPR-101. We currently have manufacturing arrangements for Validive and camsirubicin. We have not yet secured manufacturing agreements for MNPR-101-Zr, MNPR-101 RIT or MNPR-202.
Completion of our clinical trials and commercialization of our product candidates require access to, or development of, facilities to manufacture a sufficient supply of our product candidates. We will utilize third parties to manufacture our MNPR-101 radiopharma program and camsirubicin. We currently have manufacturing arrangements for MNPR-101-Zr and camsirubicin for clinical use.
Up to a total of 5,100,000 shares of our common stock may be issued as stock options or restricted stock units under the Amended and Restated Monopar Therapeutics Inc. 2016 Stock Incentive Plan, and stock options for the purchase of up to 2,147,790 shares of our common stock have already been granted (1,215,724 stock options are exercisable) and are outstanding along with 633,042 restricted stock units that have been granted to non-employee directors and employees as of March 10, 2023.
Up to a total of 5,100,000 shares of our common stock may be issued as stock options or restricted stock units under the Amended and Restated Monopar Therapeutics Inc. 2016 Stock Incentive Plan, and stock options for the purchase of up to 2,119,001 shares of our common stock have already been granted (1,553,867 stock options are exercisable) and are outstanding along with 410,136 restricted stock units that have been granted to non-employee directors and employees as of March 8, 2024.
Such testing involves a risk of liability for personal injury to or death of patients due to, among other causes, adverse side effects, improper administration of the new drug, or improper volunteer behavior.
Clinical research involves the testing of new drugs on human volunteers pursuant to a clinical trial protocol. Such testing involves a risk of liability for personal injury to or death of patients due to, among other causes, adverse side effects, improper administration of the new drug, or improper volunteer behavior.
In addition, at this stage, we are unable to predict whether the war will have broader adverse impacts to European, U.S. or global economic, trade and financial market conditions, which could adversely affect our operations and financial condition in a variety of ways. In particular, financial market instability or volatility may make it more difficult to raise required financing.
In addition, at this stage, we are unable to predict whether the wars and resulting instability will have broader adverse impacts to European, U.S. or global economic, trade and financial market conditions, which could adversely affect our operations and financial condition in a variety of ways.
There can be no assurance that we would be successful in locating an alternative source of supply or in negotiating acceptable terms with such prospective supplier.
There can be no assurance that we would be successful in locating an alternative source of supply or in negotiating acceptable terms with such prospective supplier. We rely on a limited number of contracted manufacturing plants.
If we need to enlist new contract manufacturers, it will delay our camsirubicin clinical program and may increase our cost for our Phase 1b and future camsirubicin clinical trials. We rely on third parties to conduct our non-clinical studies and our clinical trials.
If we need to enlist new contract manufacturers, it will delay our MNPR-101-Zr clinical program and may increase our cost for the currently ongoing or future clinical trials. We rely on third parties to conduct our non-clinical studies and our clinical trials.
We have 13,193,172 outstanding shares of our common stock as of March 10, 2023. A majority of our outstanding shares of common stock are currently held by non-employee directors, executive officers and other affiliates and are subject to volume limitations under Rule 144 under the Securities Act of 1933, as amended (Securities Act).
We have 17,454,925 outstanding shares of our common stock as of March 8, 2024. A substantial portion of our outstanding shares of common stock are currently held by non-employee directors, executive officers and other affiliates and are subject to volume limitations under Rule 144 under the Securities Act of 1933, as amended (Securities Act).
If we fail to satisfy the continued listing requirements of The Nasdaq Capital Market, such as the corporate governance requirements or the minimum closing bid price requirement, the Nasdaq Stock Market (“Nasdaq”) may take steps to de-list our common stock.
If we fail to satisfy other continued listing requirements of The Nasdaq Capital Market, such as, but not limited to, the corporate governance requirements, the Nasdaq Stock Market (“Nasdaq”) may take steps to de-list our common stock.
Our operations and financial results could be adversely impacted by COVID-19, which may negatively impact our ability to manufacture our product candidates for our clinical trials, our ability to accrue and conduct our clinical trials, and may delay regulatory agency responses. Any such impact will negatively impact our financial condition and could require us to delay our clinical development programs.
Our operations and financial results could be adversely impacted by resurgences of COVID-19 or any future pandemics, which may negatively impact our ability to manufacture our product candidates for our clinical trials, our ability to accrue and conduct our clinical trials, and may delay regulatory agency responses.
The Russia-Ukraine war is a volatile situation, resulting in financial services and banking instability in the region. The U.S. and other countries’ sanctions against Russia and Russian entities, together with existing inflationary conditions and supply chain challenges arising in the wake of COVID-19, are affecting fuel costs and shipping, resulting in higher costs and delays for various types of supplies.
The U.S. and other countries’ sanctions against Russia and Russian entities, together with existing inflationary conditions and supply chain challenges arising in the wake of the Israel-Hamas war, are affecting fuel costs and shipping, resulting in higher costs and delays for various types of supplies.
The CCPA will require covered companies to provide new disclosure to consumers about such companies’ data collection, use and sharing practices, provide such consumers new ways to opt-out of certain sales or transfers of personal information, and provide consumers with additional causes of action.
The CCPA requires covered companies to provide new disclosure to consumers about such companies’ data collection, use and sharing practices, provide such consumers new ways to opt-out of certain sales or transfers of personal information, and provide consumers with additional causes of action. The CCPA went into effect on January 1, 2020, and certain amendments went into effect in 2023.
We also have jointly applied for patents with our collaborator, NorthStar, for MNPR-101-Zr and MNPR-101 RIT conjugates. The patent process is subject to numerous risks and uncertainties, and there can be no assurance that we will be successful in obtaining and defending patents. See “Business - Intellectual Property Portfolio and Exclusivity”.
We are currently prosecuting this patent in other countries around the world to further protect MNPR-101. We also have jointly applied for patents with our collaborator, NorthStar, for MNPR-101-Zr and MNPR-101-RIT conjugates. The patent process is subject to numerous risks and uncertainties, and there can be no assurance that we will be successful in obtaining and defending patents.
Our common stock has only been trading on the Nasdaq Capital Market since December 19, 2019, and has experienced significant volatility in market prices through March 10, 2023, ranging from a low of $1.39 to a high of $48.00. Our small public float and relatively low and inconsistent trading volumes exacerbate volatility.
Our common stock has only been trading on the Nasdaq Capital Market since December 19, 2019, and has experienced significant volatility in market prices through March 8, 2024, ranging from a low of $0.274 to a high of $48.00.
In addition, a lack of development and commercialization collaborations may lead to significant delays in introducing proposed products into certain markets and/or reduced sales of proposed products in such markets. Furthermore, current and future collaborators may act deliberately or inadvertently in ways detrimental to our interests.
In addition, a lack of development and commercialization collaborations may lead to significant delays in introducing proposed products into certain markets and/or reduced sales of proposed products in such markets.
We have also been granted in the U.S. and various countries around the world patents to a specific sequence of amino acids on uPAR, to which our MNPR-101 antibody binds. We are currently prosecuting this patent in other countries around the world to further protect MNPR-101.
We filed and have been granted in the U.S. and various countries around the world patents for antibodies that target uPAR for our MNPR-101 program. We have also been granted in the U.S. and various countries around the world patents to a specific sequence of amino acids on uPAR, to which our MNPR-101 antibody binds.
Politically divided governmental actions and related political actions outside of government can impact the FDA’s role in the timely and effective review of new pharmaceutical products in the U.S. and our business may be adversely impacted.
Politically divided governmental actions and related political actions outside of government can impact the FDA ’ s role in the timely and effective review of new pharmaceutical products in the U.S. and our business may be adversely impacted. In recent years, there has been significant political conflict around budgeting and governmental funding of operations in the U.S. Government.
Failure to secure any necessary financing in a timely manner and on favorable terms will have a material adverse effect on our business strategy and financial performance, and could require us to cease or delay our operations. Risks Related to Clinical Development and Regulatory Approval We do not have and may never have any approved products on the market.
Failure to secure any necessary financing in a timely manner and on favorable terms will have a material adverse effect on our business strategy and financial performance, and could require us to cease or delay our operations.

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Item 2. Properties

Properties — owned and leased real estate

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Biggest changeItem 2. Properties We are currently leasing office space for our executive headquarters at 1000 Skokie Blvd in the Village of Wilmette, Illinois for our corporate offices. We believe that we will lease additional office space within the next 12 months as we continue to hire additional personnel.
Biggest changeItem 2. Properties While we are currently on a month-to-month lease for our executive headquarters at 1000 Skokie Blvd in the Village of Wilmette, Illinois for our corporate offices, we may enter into a longer-term lease in the next twelve months.

Item 5. Market for Registrant's Common Equity

Market for Common Equity — stock, dividends, buybacks

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Biggest changeRecent Sales of Unregistered Securities. There were no securities issuances that were not registered under the Securities Act during the reporting period. 64 Table of Contents
Biggest changeThrough the date hereof, TacticGem has not required us to file such a resale registration statement, although there can be no assurance we will not be required to do so in the future. Recent Sales of Unregistered Securities. There were no securities issuances that were not registered under the Securities Act during the reporting period.
Item 5. Market for Registrant’s Common Equity, Related Stockholder Matters and Issuer Purchases of Equity Securities Market Information Our common stock is listed under the symbol “MNPR” on the Nasdaq Capital Market. Holders As of March 10, 2023, there were 13,193,172 shares of our common stock outstanding held by 30 holders of record and approximately 2,700 beneficial stockholders.
Item 5. Market for Registrant ’ s Common Equity, Related Stockholder Matters and Issuer Purchases of Equity Securities Market Information Our common stock is listed under the symbol “MNPR” on the Nasdaq Capital Market. Holders As of March 8, 2024, there were 17,454,925 shares of our common stock outstanding held by 30 holders of record and approximately 3,200 beneficial stockholders.
Removed
We are required to use our best efforts to have such registration statement declared effective as soon as practical after it is filed.
Removed
In the event that such registration statement for resale is not approved by the SEC, and TacticGem submits a written request, we are required to prepare and file a registration statement on Form S-1 registering such common stock for resale and to use our best efforts to have such registration statement declared effective as soon as practical thereafter.
Removed
Additionally, if we propose to register our common stock for sale for cash, TacticGem and its members have the right to include some of their shares in such registration After registration, pursuant to these rights, these shares will become freely tradable without restriction under the Securities Act other than pursuant to restrictions on affiliates under Rule 144.

Item 7. Management's Discussion & Analysis

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

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Biggest changeExpenditures are expected to increase in 2023 and onward for: · assuming a positive result of the go/no go interim analysis decision anticipated by the end of March 2023, clinical research services and clinical site fees for our Phase 3 VOICE clinical program, including, if required, completing a second Phase 3 confirmatory clinical trial; · process development, manufacturing costs, clinical trial expenses and clinical database management of camsirubicin in connection with the Phase 1b dose escalation clinical trial and other future clinical development; · support of the development of MNPR-101-derived radioimmunotherapeutics (MNPR-101 RIT) and companion diagnostics (MNPR-101-Zr) to treat cancer, including activities through our collaboration with NorthStar; · preclinical studies (and if successful, clinical studies) of MNPR-202 (and related analogs); and · employee compensation and consulting fees to support the increased scope of activities required for the progress of our product candidate programs including Validive, camsirubicin, MNPR-101 RIT (uPRIT and related compounds) and companion diagnostics (MNPR-101-Zr) and MNPR-202 (and related analogs).
Biggest changeExpenditures are expected to increase in 2024 and onward for: ● development of our MNPR-101 radiopharma program to image and treat various advanced cancers; ● Development of our camsirubicin program if data support development beyond Phase 1b; ● development of potential new in-licensed product candidates; ● employee compensation and consulting fees to support the increased scope of activities required for the progress of our product candidate programs including MNPR-101 for radiopharmaceutical use, camsirubicin, and MNPR-202 (and related analogs) We are working towards initiating enrollment for our MNPR-101-Zr Phase 1 dosimetry clinical trial.
We plan to continue the expansion of our drug development pipeline through acquiring or in-licensing additional oncology product candidates, particularly those that leverage existing scientific and clinical data that helps reduce the risks of the next steps in clinical development. · Utilize the expertise and prior experience of our team in the areas of asset acquisition, drug development and commercialization to establish ourselves as a leading biopharmaceutical company.
We plan to continue the expansion of our drug development pipeline through acquiring or in-licensing additional product candidates, particularly those that leverage existing scientific and clinical data that helps reduce the risks of the next steps in clinical development. ● Utilize the expertise and prior experience of our team in the areas of asset acquisition, drug development and commercialization to establish ourselves as a leading biopharmaceutical company.
In aggregate, our team has co-founded BioMarin Pharmaceutical (Nasdaq: BMRN), Sensant Corp (acquired by Siemens), American BioOptics (assets acquired by Olympus), Raptor Pharmaceuticals ($800 million sale to Horizon Therapeutics), and Tactic Pharma, LLC (“Tactic Pharma”) (sale of lead asset, choline tetrathiomolybdate, was ultimately acquired by Alexion in June 2018 for $764 million; Alexion was subsequently acquired by AstraZeneca). 67 Table of Contents Implications of Being an Emerging Growth Company We qualify as an “emerging growth company” as defined in the Jumpstart Our Business Startups Act of 2012 (“JOBS Act”).
In aggregate, our team has co-founded BioMarin Pharmaceutical (Nasdaq: BMRN), Sensant Corp (acquired by Siemens), American BioOptics (assets acquired by Olympus), Raptor Pharmaceuticals ($800 million sale to Horizon Therapeutics), and Tactic Pharma, LLC (“Tactic Pharma”) (sale of lead asset, choline tetrathiomolybdate, was ultimately acquired by Alexion in June 2018 for $764 million; Alexion was subsequently acquired by AstraZeneca). 61 Table of Contents Implications of Being an Emerging Growth Company We qualify as an “emerging growth company” as defined in the Jumpstart Our Business Startups Act of 2012 (“JOBS Act”).
Our primary funding source over the past three years was sales of shares of our common stock under at-the-market sales programs through Capital on Demand TM Sales Agreements with JonesTrading Institutional Services LLC (“Jones Trading”).
Our primary funding source over the past three years was sales of shares of our common stock under at-the-market sales programs through Capital on Demand™ Sales Agreements with JonesTrading Institutional Services LLC (“Jones Trading”).
We will require additional funding to advance our clinical and preclinical programs and we anticipate that we will seek to raise additional capital within the next 12 months to fund our future operations.
We will require additional funding to further advance our clinical and preclinical programs and we anticipate that we will seek to raise additional capital within the next 12 months to fund our future operations.
The expected term for stock options granted during the years ended December 31, 2022, and 2021, was estimated using the simplified method. Forfeitures only include actual forfeitures to-date as the Company accounts for forfeitures as they occur due to a limited history of forfeitures.
The expected term for stock options granted during the years ended December 31, 2023 and 2022, was estimated using the simplified method. Forfeitures only include actual forfeitures to-date as the Company accounts for forfeitures as they occur due to a limited history of forfeitures.
The 2-pyrrilino camsirubicin analog (MNPR-202) and related analogs represent proprietary compositions of matter designed to retain the non-cardiotoxic backbone of camsirubicin yet exhibit novel features in terms of antitumor activity and mechanism that distinguish these analogs from camsirubicin as well as from doxorubicin , potentially addressing camsirubicin- and doxorubicin-resistant cancers . · Expand our drug development pipeline through advancing current assets, in-licensing, and acquisition of oncology product candidates.
The 2-pyrrilino camsirubicin analog (MNPR-202) and related analogs represent proprietary compositions of matter designed to retain the non-cardiotoxic backbone of camsirubicin yet exhibit novel features in terms of antitumor activity and mechanism that distinguish these analogs from camsirubicin as well as from doxorubicin, potentially addressing camsirubicin- and doxorubicin-resistant cancers. ● Expand our drug development pipeline through in-licensing and acquisition of product candidates.
Cash Flow Used in Operating Activities The cash flow used in operating activities during the year ended December 31, 2022, compared to the year ended December 31, 2021 was essentially flat.
Cash Flow Used in Operating Activities The cash flow used in operating activities during the year ended December 31, 2023, compared to the year ended December 31, 2022 was essentially flat.
In aggregate, companies they co-founded have achieved four drug approvals and three diagnostic medical imaging device approvals in the U.S. and the EU, successfully sold an asset developed by management which is currently in Phase 3 clinical trials, sold two oncology-focused diagnostic imaging businesses to Fortune Global 1000 firms, and completed the clinical and commercial development and ultimately the sale of a commercial biopharmaceutical company for over $800 million in cash.
In aggregate, companies they co-founded have achieved four drug approvals and three diagnostic medical imaging device approvals in the U.S. and the EU, successfully sold an asset developed by management which subsequently had a positive Phase 3 clinical trial, sold two oncology-focused diagnostic imaging businesses to Fortune Global 1000 firms, and completed the clinical and commercial development and ultimately the sale of a commercial biopharmaceutical company for over $800 million in cash.
Item 7. Management’s Discussion and Analysis of Financial Condition and Results of Operations. You should read the following discussion and analysis of our financial condition and results of operations together with our financial statements and related notes appearing at the end of this Annual Report on Form 10-K.
Item 7. Management ’ s Discussion and Analysis of Financial Condition and Results of Operations. You should read the following discussion and analysis of our financial condition and results of operations together with our financial statements and related notes appearing at the end of this Annual Report on Form 10-K.
Our future capital requirements will depend on many factors, including: · the progress of clinical development and regulatory interactions and approvals of Validive; · the progress of clinical development and regulatory interactions and approvals of camsirubicin; · the costs, timing and outcomes of seeking, obtaining, and maintaining FDA and international regulatory approvals; · the progress of preclinical and clinical development of MNPR-101-derived radioimmunotherapeutics and companion diagnostics, to treat cancer, including activities through our collaboration with NorthStar; · the progress of preclinical and potentially clinical development of MNPR-202 (and related analogs); · the number and characteristics of other drug product candidates that we may license, acquire, invent or otherwise pursue; · the scope, progress, timing, cost and results of research, preclinical development and clinical trials and regulatory requirements for future drug product candidates; 72 Table of Contents · the costs associated with manufacturing/quality requirements and establishing or contracting for sales, marketing and distribution capabilities; · our ability to maintain, expand and defend the scope of our intellectual property portfolio, including the amount and timing of any payments we may be required to make in connection with the licensing, filing, defense and enforcement of any patents or other intellectual property rights; · our need and ability to hire or contract for additional management, administrative, scientific, medical, sales and marketing, and manufacturing/quality and other specialized personnel or external expertise; · the effect and timing of entry of competing products or new therapies that may limit market penetration or prevent the introduction of our drug product candidates or reduce the commercial potential of our product portfolio; · our need to implement additional required internal management, operational, record keeping and other systems and infrastructure; and · the economic and other terms, timing and success of our existing collaboration and licensing arrangements and any collaboration, licensing or other arrangements into which we may enter in the future, including the timing of receipt of or payment to or from others of any license, milestone or royalty payments under these arrangements.
Our future capital requirements will depend on many factors, including: ● the progress of clinical development and regulatory interactions and approvals of our MNPR-101 radiopharma program; ● the progress of clinical development and regulatory interactions and approvals of camsirubicin; ● the costs, timing and outcomes of seeking, obtaining, and maintaining FDA, TGA and other international regulatory approvals; ● the progress of preclinical and potentially clinical development of MNPR-202 (and related analogs); ● the number and characteristics of other drug product candidates that we may license, acquire, invent or otherwise pursue; ● the scope, progress, timing, cost and results of research, preclinical development and clinical trials and regulatory requirements for future drug product candidates; 66 Table of Contents ● the costs associated with manufacturing/quality requirements, establishing a reliable supply chain, and establishing or contracting for sales, marketing and distribution capabilities; ● our ability to maintain, expand and defend the scope of our intellectual property portfolio, including the amount and timing of any payments we may be required to make in connection with the licensing, filing, defense and enforcement of any patents or other intellectual property rights; ● our need and ability to hire or contract for additional management, administrative, scientific, medical, sales and marketing, and manufacturing/quality and other specialized personnel or external expertise; ● the effect and timing of entry of competing products or new therapies that may limit market penetration or prevent the introduction of our drug product candidates or reduce the commercial potential of our product portfolio; ● our need to implement additional required internal management, operational, record keeping and other systems and infrastructure; and ● the economic and other terms, timing and success of our existing collaboration and licensing arrangements and any collaboration, licensing or other arrangements into which we may enter in the future, including the timing of receipt of or payment to or from others of any license, milestone or royalty payments under these arrangements.
We expect that our R&D and G&A expenses will increase to enable the execution of our strategic plan. As a result, we anticipate that we will seek to raise additional capital within the next 12 months to fund our future operations.
We anticipate that we will continue to incur losses for the foreseeable future. We expect that our R&D and G&A expenses will increase to enable the execution of our strategic plan. As a result, we anticipate that we will seek to raise additional capital within the next 12 months to fund our future operations.
Determining the appropriate fair value model and related assumptions requires judgment, including selecting methods for estimating our future stock price volatility and expected holding term. The expected volatility rates are estimated based on our actual historical volatility over the two-year period from our initial public offering on December 18, 2019, through December 31, 2021.
Determining the appropriate fair value model and related assumptions requires judgment, including selecting methods for estimating our future stock price volatility and expected holding term. For options granted in 2023, the expected volatility rates are estimated based on our actual historical volatility over the three-year period from our initial public offering on December 18, 2019, through December 31, 2022.
We anticipate that the funds available as of March 10, 2023, will fund our obligations at least through March 31, 2024. We have based this estimate on assumptions that may prove to be wrong, and we could use our available capital resources sooner than we currently expect.
We anticipate that the funds available as of March 8, 2024, will fund our obligations at least through June 30, 2025. We have based this estimate on assumptions that may prove to be wrong, and we could use our available capital resources sooner than we currently expect.
In addition, we are also a “smaller reporting company” as defined in Rule 12b-2 of the Exchange Act and have elected to take advantage of certain of the scaled back disclosure requirements available to smaller reporting companies such as avoiding the extensive narrative disclosure required of other reporting companies, particularly in the description of executive compensation. 68 Table of Contents Revenues We are an emerging growth company.
In addition, we are also a “smaller reporting company” as defined in Rule 12b-2 of the Exchange Act and have elected to take advantage of certain of the scaled back disclosure requirements available to smaller reporting companies such as avoiding the extensive narrative disclosure required of other reporting companies, particularly in the description of executive compensation.
Treasury Bills. 70 Table of Contents Cash Flows The following table provides information regarding our cash flows for the years ended December 31, 2022, and 2021.
Treasury Bills. 64 Table of Contents Cash Flows The following table provides information regarding our cash flows for the years ended December 31, 2023, and 2022.
We anticipate that the currently available funds as of March 10, 2023, will fund our planned operations at least through March 31, 2024. We invest our cash equivalents in two money market accounts and U.S.
We anticipate that the currently available funds as of March 8, 2024, will fund our planned operations at least through June 30, 2025. We invest our cash equivalents in two money market accounts and U.S.
We anticipate that our expenses will increase substantially as we: · advance the clinical development and execute the regulatory strategy for Validive, assuming a positive result of the go/no go interim analysis decision anticipated by the end of March 2023; · advance the clinical development and execute the regulatory strategy for camsirubicin; · continue the preclinical activities and potentially enter clinical development of an MNPR-101-derived radioimmunotherapeutics (MNPR-101 RIT) and companion diagnostics (MNPR-101-Zr), to treat cancer; · continue the preclinical activities, and potentially later-on enter clinical development, of MNPR-202 (and related analogs) for various cancer indications; · acquire and/or license additional pipeline drug product candidates and pursue the future preclinical and/or clinical development of such drug product candidates; 71 Table of Contents · seek regulatory approvals for any of our current and future drug product candidates that successfully complete registration clinical trials; · establish or purchase the services of a sales, marketing and distribution infrastructure to commercialize any products for which we obtain marketing approval; · develop or contract for manufacturing/quality capabilities or establish a reliable, high quality supply chain sufficient to support our clinical requirements and to provide sufficient capacity to launch and supply the market for any product for which we obtain marketing approval; and · add or contract for required operational, financial and management information systems and capabilities and other specialized expert personnel to support our drug product candidate development and planned commercialization efforts.
We anticipate that our expenses will increase substantially as we: ● continue the clinical and preclinical activities of MNPR-101-Zr and MNPR-101-RIT to image and treat cancer; ● advance the clinical development for camsirubicin; ● continue the preclinical activities, and potentially later-on enter clinical development, of MNPR-202 (and related analogs) for various cancer indications; 65 Table of Contents ● acquire and/or license additional pipeline drug product candidates and pursue the future preclinical and/or clinical development of such drug product candidates; ● seek regulatory approvals for any of our current and future drug product candidates that successfully complete registration clinical trials; ● establish or purchase the services of a sales, marketing and distribution infrastructure to commercialize any products for which we obtain marketing approval; ● develop or contract for manufacturing/quality capabilities or establish a reliable, high quality supply chain sufficient to support our clinical requirements and to provide sufficient capacity to launch and supply the market for any product for which we obtain marketing approval; and ● add or contract for required operational, financial and management information systems and capabilities and other specialized expert personnel to support our drug product candidate development and planned commercialization efforts.
Contractual Obligations and Commitments License, Development and Collaboration Agreements Onxeo S.A. In June 2016, we executed an agreement with Onxeo S.A., a French public company, which gave us the exclusive option to license (on a world-wide exclusive basis) Validive (clonidine hydrochloride mucobuccal tablet; clonidine HCI MBT a mucoadhesive tablet of clonidine based on the Lauriad mucoadhesive technology.
In June 2016, we executed an agreement with Onxeo S.A., a French public company, which gave us the exclusive option to license (on a world-wide exclusive basis) Validive (clonidine hydrocholoride mucobuccal tablet; clonidine HCI MBT) a mucoadhesive tablet of clonidine based on the Lauriad mucoadhesive technology.
Pursuant to a non-exclusive license agreement with XOMA Ltd. for the humanization technology used in the development of MNPR-101, we are obligated to pay XOMA Ltd. clinical, regulatory and sales milestones which could reach up to $14.925 million if we achieve all milestones for MNPR-101. The agreement does not require the payment of sales royalties.
Contractual Obligations and Commitments License, Development and Collaboration Agreements XOMA Ltd. Pursuant to a non-exclusive license agreement with XOMA Ltd. for the humanization technology used in the development of MNPR-101, we are obligated to pay XOMA Ltd. clinical, regulatory and sales milestones which could reach up to $14.925 million if we achieve all milestones for MNPR-101.
We have no approved drugs and have not generated any revenues. To date, we have engaged in acquiring or in-licensing drug product candidates, entering into collaboration agreements for testing and clinical development of our drug product candidates and providing the infrastructure to support the clinical development of our drug product candidates.
To date, we have engaged in acquiring or in-licensing drug product candidates, entering into collaboration agreements for testing and clinical development of our drug product candidates and providing the infrastructure to support the clinical development of our drug product candidates.
Cash Flow Provided by Financing Activities The decrease in cash flow provided by financing activities during the year ended December 31, 2022, compared to the year ended December 31, 2021, of approximately $10,846,000 was primarily due to higher net proceeds from sales of our common stock through an at-the-market sales program in 2021.
Cash Flow Provided by Financing Activities The increase in cash flow provided by financing activities during the year ended December 31, 2023 , compared to the year ended December 31, 2022 , of $1,994,000 was primarily due to higher net proceeds from sales of our common stock through an at-the-market sales program.
General and Administrative (“G&A") Expenses G&A expenses for the year ended December 31, 2022, were $2,945,000, compared to $2,634,000 for the year ended December 31, 2021.
General and Administrative ( " G&A") Expenses G&A expenses for the year ended December 31, 2023 , were $3,231,000, compared to $2,945,000 for the year ended December 31, 2022 .
There can be no assurance that we will achieve any milestones. As of March 10, 2023, we had not reached any milestones and had not been required to pay XOMA Ltd. any funds under this license agreement.
The agreement does not require the payment of sales royalties. There can be no assurance that we will achieve any milestones. As of March 8, 2024, we had not reached any milestones and had not been required to pay XOMA Ltd. any funds under this license agreement.
We could also enter into collaborative research and development, contract research, manufacturing and supplier agreements in the future, which may require upfront payments and/or long-term commitments of cash.
We can elect to discontinue the work under these agreements at any time. We could also enter into collaborative research and development, contract research, manufacturing and supplier agreements in the future, which may require upfront payments and/or long-term commitments of cash.
You should read the “Risk Factors” section of this Annual Report on Form 10-K, Item 1A, for a discussion of important factors that could cause actual results to differ materially from the results described in or implied by the forward-looking statements contained in the following discussion and analysis.
You should read the “Risk Factors” section of this Annual Report on Form 10-K, Item 1A, for a discussion of important factors that could cause actual results to differ materially from the results described in or implied by the forward-looking statements contained in the following discussion and analysis. 59 Table of Contents Overview We are a clinical stage biopharmaceutical company focused on developing innovative treatments for cancer patients.
We have elected to take advantage of certain of the reduced disclosure obligations in this Annual Report on Form 10-K, and may elect to take advantage of other reduced reporting requirements in future filings.
We expect to no longer qualify as an emerging growth company at the end of 2024. We have elected to take advantage of certain of the reduced disclosure obligations in this Annual Report on Form 10-K, and may elect to take advantage of other reduced reporting requirements in future filings.
Identifying and securing high-quality compounds usually takes time and related expenses; however, our spending could be significantly accelerated in 2023 and onward if additional drug product candidates are acquired and enter clinical development.
We intend to continue evaluating drug product candidates for the purpose of growing our pipeline. Identifying and securing high-quality compounds usually takes time and related expenses; however, our spending could be significantly accelerated in 2024 and onward if additional drug product candidates are acquired and enter clinical development.
We will seek to obtain needed capital through a combination of equity offerings, including the usage of our Capital on Demand TM Sales Agreement with JonesTrading, debt financings, strategic collaborations and grant funding.
We will seek to obtain needed capital through a combination of equity offerings, including at-the-market sales programs, debt financings, strategic collaborations and grant funding.
Beyond our need to raise additional funding within the next 12 months to complete the VOICE clinical program, additional long-term funding is needed to commercialize Validive, if approved, and otherwise generally to support our current and future product candidates through clinical trials, approval processes and, if applicable, commercialization. 73 Table of Contents Until we can generate a sufficient amount of product revenue to finance our cash requirements, we expect to finance our future cash needs primarily through a combination of equity offerings, including the usage of our Capital on Demand™ Sales Agreement with JonesTrading, debt financings, strategic collaborations and grant funding.
Additional long-term funding is needed to generally to support our current and future product candidates through clinical trials, approval processes and, if applicable, commercialization. 67 Table of Contents Until we can generate a sufficient amount of product revenue to finance our cash requirements, we expect to finance our future cash needs primarily through a combination of equity offerings, including at-the-market sales programs, debt financings, strategic collaborations and grant funding.
Treasury securities with maturities consistent with the estimated expected term of the awards. 69 Table of Contents Results of Operations Comparison of the Years Ended December 31, 2022, and December 31, 2021 The following table summarizes the results of our operations for the years ended December 31, 2022, and 2021: Years Ended December 31, (in thousands) 2022 2021 Variance Research and development expenses $ 7,592 $ 6,493 $ 1,099 General and administrative expenses 2,945 2,634 311 Total operating expenses 10,537 9,127 1,410 Operating loss (10,537 ) (9,127 ) (1,410 ) Interest income 21 24 (3 ) Net loss $ (10,516 ) $ (9,103 ) $ (1,413 ) Research and Development (“R&D”) Expenses R&D expenses for the year ended December 31, 2022 were $7,592,000, compared to $6,493,000 for the year ended December 31, 2021.
Treasury securities with maturities consistent with the estimated expected term of the awards. 63 Table of Contents Results of Operations Comparison of the Years Ended December 31, 2023, and December 31, 2022 The following table summarizes the results of our operations for the years ended December 31, 2023, and 2022: Year Ended December 31, (in thousands) 2023 2022 Variance Research and development expenses $ 5,600 $ 7,592 $ (1,992 ) General and administrative expenses 3,231 2,945 286 Total operating expenses 8,831 10,537 (1,706 ) Operating loss (8,831 ) (10,537 ) 1,706 Interest income 429 21 408 Net loss $ (8,402 ) $ (10,516 ) $ 2,114 Research and Development ( “ R&D ” ) Expenses R&D expenses for the year ended December 31, 2023 were $5,600,000, compared to $7,592,000 for the year ended December 31, 2022 .
Our current ongoing Phase 1b clinical trial continues towards establishing a new, higher recommended dose for the next Phase 2 ASTS clinical trial. · Continue the development of MNPR-101-Zr, MNPR-101 RIT and related molecules as therapeutic, diagnostic and imaging agents.
Our current ongoing Phase 1b clinical trial continues towards establishing a new, higher recommended dose for the next Phase 2 ASTS clinical trial. ● Continue the development of MNPR-202 and related analogs in multiple types of cancers.
Service Providers In the normal course of business, we contract with service providers to assist in the performance of R&D, including drug product manufacturing, process development, clinical and preclinical development, and G&A including financial strategy, audit, tax and legal support. We can elect to discontinue the work under these agreements at any time.
We have not incurred any license or royalty obligations and the license has been terminated effective January 2024. 68 Table of Contents Service Providers In the normal course of business, we contract with service providers to assist in the performance of R&D, including drug product manufacturing, process development, clinical and preclinical development, and G&A including financial strategy, audit, tax and legal support.
Cash Flow Used in Investing Activities The increase to cash flow used in investing activities during the year ended December 31, 2022, compared to the year ended December 31, 2021 of approximately $4,919,000 was a result of our investment in U.S. Treasury Bills at the end of 2022.
Cash Flow Used in Investing Activities The increase to cash flow provided by investing activities during the year ended December 31, 2023 , compared to cash used in investing activities during the year ended December 31, 2022 , of $9,847,000 was related to the fact that our investment in U.S.
This represents an increase of $311,000 primarily attributed to (1) a $349,000 increase in G&A personnel salaries, bonuses, benefits and stock-based compensation for annual (non-cash) equity grants, and (2) a $27,000 net increase in other G&A expenses partially offset by a $65,000 decrease in patent costs.
This represents an increase of $286,000 primarily attributed to a $220,000 increase in G&A personnel salaries, bonuses, benefits and stock-based compensation for annual (non-cash) equity grants, and a $66,000 net increase in other G&A expenses. Interest Income Interest income for the year ended December 31, 2023 , increased by $408,000 versus the year ended December 31, 2022 .
Liquidity and Capital Resources Sources of Liquidity We have incurred losses and cumulative negative cash flows from operations since we commenced operations resulting in an accumulated deficit of approximately $51.8 million as of December 31, 2022. We anticipate that we will continue to incur losses for the foreseeable future.
The increase is due to interest earned on treasury bills and money market accounts that yielded higher interest rates in 2023 . Liquidity and Capital Resources Sources of Liquidity We have incurred losses and cumulative negative cash flows from operations since we commenced operations resulting in an accumulated deficit of approximately $60.2 million as of December 31, 2023.
However, we may record charges in the future as a result of these indemnification obligations.
To date, we have not paid any claims or been required to defend any action related to our indemnification obligations. However, we may record charges in the future as a result of these indemnification obligations.
Our exposure under these agreements is unknown because it involves claims that may be made against us in the future, but that have not yet been made. To date, we have not paid any claims or been required to defend any action related to our indemnification obligations.
Indemnification In the normal course of business, we enter into contracts and agreements that contain a variety of representations and warranties and provide for general indemnification. Our exposure under these agreements is unknown because it involves claims that may be made against us in the future, but that have not yet been made.
Our strategic goal is to acquire, develop and commercialize promising oncology product candidates that address important unmet medical needs of cancer patients.
Our strategic goal is to acquire, develop and commercialize promising oncology product candidates that address important unmet medical needs of cancer patients. Five key elements of our strategy to achieve this goal are to: ● Continue the development of MNPR-101 for radiopharmaceutical use as a therapeutic as well as a diagnostic imaging agent .
Office Lease We are currently leasing office space for our executive headquarters at 1000 Skokie Blvd., in the Village of Wilmette, Illinois for $4,238 per month through February 2024, and we anticipate that we will lease additional space in the future as we hire additional personnel.
Office Lease We are currently leasing office space on a month-to-month basis for our executive headquarters at 1000 Skokie Blvd., in the Village of Wilmette, Illinois for $4,238 per month. Legal Contingencies We are currently not, and to date have never been, a party to any adverse material legal proceedings.
During 2020 and the first quarter of 2021, we sold 1,964,724 shares of our common stock at an average gross price of $10.02 per share for net proceeds of $19,100,603, after fees and commissions of $591,188.
For the year ended December 31, 2023, we sold 1,793,441 shares of our common stock at an average gross price per share of $1.21 for net proceeds of $2,072,503 after fees, commissions and expenses of $98,230.
During the years ended December 31, 2022 and 2021, we had net cash outflows of $12,118,000 and net cash inflows of $3,567,000, respectively, a decrease of $15,685,000. During 2022, we had higher net cash used investing activities and less funds raised from sales of our common stock under an at-the-market sales program compared to 2021.
During 2023 , we had net cash provided by investing activities as some of our investments made in 2022 matured and were used in operating activities, as well as higher net cash provided by financing activities due to more funds raised from sales of our common stock under an at-the-market sales program compared to 2022 .
Overview We are a clinical stage biopharmaceutical company focused on developing proprietary therapeutics designed to extend life or improve quality of life for cancer patients. We are building a drug development pipeline through the licensing and acquisition of therapeutics in late preclinical or in clinical development stages.
We are building a drug development pipeline through the licensing and acquisition of therapeutics in late preclinical or in clinical development stages. We leverage our scientific and clinical experience to help reduce the risk of and accelerate the clinical development of our drug product candidates.
This represents an increase of $1,099,000 primarily attributed to (1) a $1,044,000 increase for Validive clinical trial planning and execution including manufacturing costs, (2) a $460,000 increase due to camsirubicin clinical trial planning and execution including manufacturing costs, (3) a $193,000 increase in R&D consulting, partially offset by (1) a $534,000 decrease for R&D personnel salaries, bonuses, benefits and annual (non-cash) equity grants and (2) a $64,000 net decrease in other R&D expenses.
This represents a decrease of $1,992,000 primarily attributed to (1) a $1,375,000 decrease for Validive clinical trial and manufacturing costs as a result of the termination of that program in March 2023, (2) a $904,000 decrease for a reduction in camsirubicin clinical trial and manufacturing costs, (3) a $126,000 decrease in R&D salaries, partially offset by (1) a $408,000 increase related to MNPR-101 radiopharma activity and (2) a $5,000 net increase in other R&D expenses.
Years Ended December 31, (in thousands) 2022 2021 Variance Net cash used in operating activities $ (7,228 ) $ (7,317 ) $ 89 Net cash used in investing activities (4,919 ) - (4,919 ) Net cash provided by financing activities 33 10,879 (10,846 ) Effect of exchange rates (4 ) 5 (9 ) Net increase (decrease) in cash and cash equivalents $ (12,118 ) $ 3,567 $ (15,685 ) During 2022, the Company began investing its idle cash due to the rising interest rates and at December 31, 2022, the Company holds short term liquid investments of $4,934,000 which can be readily converted to cash.
Year Ended December 31, (in thousands) 2023 2022 Variance Net cash used in operating activities $ (7,858 ) $ (7,228 ) $ (630 ) Net cash provided by (used in) investing activities 4,928 (4,919 ) 9,847 Net cash provided by fi nancing activities 2,027 33 1,994 Effect of exchange rates (17 ) (4 ) (13 ) Net decrease in cash and cash equivalents $ (920 ) $ (12,118 ) $ 11,198 During the years ended December 31, 2023 and 2022 , we had net cash outflows of $920,000 and $12,118,000, respectively, a decrease of $11,198,000.
Recently Issued and Adopted Accounting Pronouncements During the year ended December 31, 2022, there were no relevant recently issued accounting pronouncements that would impact our financial position and our consolidated results of operations and comprehensive loss or cashflows.
Recently Issued and Adopted Accounting Pronouncements During the year ended December 31, 2023, there were two recently issued accounting pronouncements that are described in more detail in Note 2 of our consolidated financial statements included elsewhere in this Annual Report on Form 10-K.
From January 1, 2023 to March 10, 2023, the Company sold 241,475 shares of its common stock at an average gross price per share of $3.47 for net proceeds of $836,836, after fees and commissions of $20,940.
From January 1 to March 8, 2024, we sold 2,545,305 shares of our common stock at an average gross price per share of $1.29 for net proceeds of $3,194,310, after fees and commissions of $81,932. MNPR-101 for Radiopharmaceutical Use, Development Update Our proprietary, novel MNPR-101 radiopharmaceutical program is a first-in-class urokinase plasminogen activator receptor ("uPAR") targeting radiopharmaceutical for advanced tumors.
Removed
We leverage our scientific and clinical experience to help reduce the risk of and accelerate the clinical development of our drug product candidates. Financial Status Our cash, cash equivalents and investments as of December 31, 2022, was $13.1 million.
Added
Financial Status Our cash, cash equivalents and investments as of December 31, 2023, were $7.3 million.
Removed
As discussed further below and elsewhere in this Annual Report, we expect that our current funds will be sufficient for us to obtain topline results from our ongoing open-label Phase 1b camsirubicin clinical trial as planned by the end of 2023 (but as discussed below, this may not be the case if camsirubicin reaches even higher dose levels than we are anticipating and topline results are deferred as dosing continues beyond 2023) and, assuming a positive result of the go/no go interim analysis decision anticipated by the end of March 2023, the continued enrollment in the Phase 3 portion of our ongoing Validive Phase 2b/3 (VOICE) clinical program.
Added
As discussed further below and elsewhere in this Annual Report, we expect that our current funds will be sufficient at least through June 30, 2025 for us to: (1) conduct and conclude our first-in-human clinical trial with our MNPR-101-Zr radiopharmaceutical program; (2) continue our ongoing open-label Phase 1b camsirubicin clinical trial; and (3) continue to research MNPR-202.
Removed
The maximum aggregate offering price under the prior agreement was reached during the first quarter of 2021 and there were no further sales under that agreement. In April 2022, we entered into a new at-the-market sales agreement.
Added
The Company's radiopharmaceutical development team has conjugated MNPR-101, its proprietary first-in-class humanized monoclonal antibody that is highly selective against uPAR, to imaging and therapeutic radioisotopes, to develop highly precise imaging and therapeutic radiopharmaceutical agents that have the potential to image and eradicate tumors expressing uPAR while sparing healthy tissues.
Removed
Pursuant to that agreement, during 2022, the Company sold 64,573 shares of its common stock at an average gross price per share of $2.71 for net proceeds of $170,552, after fees and commissions of $4,377. In addition, the Company incurred legal, accounting and other fees totaling $83,234 for net proceeds after fees, commissions and expenses of $87,318.
Added
In February 2024, the Company announced promising preclinical data and regulatory clearance in Australia to commence a first-in-human Phase 1 clinical trial of MNPR-101-Zr for imaging tumors in patients with advanced cancers. Monopar is moving aggressively towards opening enrollment to patients in this Phase 1.
Removed
Validive Clinical Update In February 2021, we dosed the first patient in our Phase 2b/3 VOICE trial of Validive® for the prevention of chemoradiation treatment (“CRT”)-induced se v ere o ral mucositis (“SOM”) in pat i ents with oropharyngeal c anc e r (“VOICE”).
Added
Camsirubicin Clinical Update The Phase 1b open-label, dose-escalating clinical trial of camsirubicin in patients with advanced soft tissue sarcoma (“ASTS”) is currently ongoing and enrolling in the fifth dose-level cohort (650 mg/m 2 ), which is nearly 2.5x the highest dose evaluated in any prior camsirubicin clinical trial (265 mg/m 2 ).
Removed
In August 2021, we successfully reached our original target of 20 activated clinical trial sites for the Phase 2b portion of the 2b/3 Validive® VOICE trial and in September 2021, we received authorization to proceed with the VOICE clinical trial in multiple countries in Europe.
Added
MNPR-202 and Related Analogs Updates MNPR-202, an analog of camsirubicin designed to potentially treat doxorubicin- and camsirubicin-resistant cancers, is being tested in preclinical models by our collaborator, the Cancer Science Institute of Singapore at the National University of Singapore.
Removed
In 2022, we completed enrollment of the Phase 2b portion of the VOICE trial and commenced enrollment in the Phase 3 portion. As of March 10, 2023, we have 81 clinical sites activated and enrolling patients in the U.S. and Europe.
Added
Discontinuation of Validive Development On March 27, 2023, we announced that based on Validive not meeting the pre-specified efficacy threshold in our interim clinical trial data analysis, we terminated the study, discontinued the development of Validive and subsequently terminated the license with Onxeo, SA. 60 Table of Contents Our Strategy Our management team has extensive experience in developing therapeutics and medical technologies through global regulatory approval and commercialization.
Removed
To be prepared for a potential positive go/no-go decision based on the interim analysis, we continue to activate additional sites globally. This interim analysis, and the resulting go/no-go decision about whether to proceed to the Phase 3 portion of the trial, is expected by the end of March 2023.
Added
Based on promising preclinical results utilizing radiolabeled MNPR-101, we have been cleared to conduct a Phase 1 dosimetry clinical trial of MNPR-101-Zr in patients with advanced cancers in Australia. ● Advance the clinical development of camsirubicin, by pursuing indications where doxorubicin has demonstrated efficacy.
Removed
If the interim analysis results in a no-go decision, we would need to reconsider our efforts with respect to Validive and refocus our development efforts on our other product candidates.
Added
Our status as a smaller reporting company will not be impacted by the loss of emerging growth company status at the end of 2024, so we may continue to take advantage of these scaled disclosure requirements so long as we qualify.
Removed
Validive has been our lead product candidate to date and is the most clinically advanced, and if we had to reconsider or abandon our efforts, it would likely materially adversely impact our financing prospects, as well as the price of our common stock.
Added
In addition, the loss of emerging growth status will not impact our “non-accelerated filer” status, which also provides an exemption from the auditor attestation requirement with respect to internal control over financial reporting. 62 Table of Contents Revenues We are an emerging growth company. We have no approved drugs and have not generated any revenues.
Removed
Because the interim analysis is being performed by an independent data monitoring committee, we do not know what the results will be as of the date of this Annual Report. 65 Table of Contents To complete the VOICE clinical program, including, if required, completing a second Phase 3 confirmatory clinical trial, we will require additional funding in the millions or tens of millions of dollars (depending on if we have consummated a collaboration or partnership or neither for Validive), which we are planning to pursue within the next 12 months.
Added
During 2022, we began investing our idle cash due to the rising interest rates, resulting in a significant increase in cash used in investing activities.
Removed
Camsirubicin Clinical Update In August 2021, we announced clearance from the U.S. Food and Drug Administration (“FDA”) to proceed with an open-label Phase 1b dose-escalation clinical trial evaluating camsirubicin plus growth factor support (pegfilgrastim/G-CSF) in patients with advanced soft tissue sarcoma (“ASTS”).
Added
Treasury Bills commenced in December 2022 with maturities reinvested or used as working capital throughout 2023.
Removed
In September 2021, we initiated the Phase 1b clinical trial, and in October 2021 we dosed the first patients.
Added
If the tumor uptake, biodistribution, and safety look encouraging in this Phase 1 dosimetry trial, we may proceed to evaluate the efficacy in humans of a therapeutically radio-labeled version of MNPR-101 bound to an isotope such as Ac-225, which will require additional funding or finding a suitable pharmaceutical partner. There can be no assurance that any such events will occur.
Removed
In February 2022, we announced that the first dose level of camsirubicin had been completed in November 2021, with a positive recommendation from the trial safety review committee to proceed to next higher dose level and that three patients had already been dosed at the second dose level.
Added
The first milestone payment is payable upon first dosing of a human patient in a Phase 2 clinical trial. Onxeo S.A .
Removed
That dose level was successfully cleared, as was the third and fourth dose levels, and we are presently enrolling patients at the fifth dose level.
Added
In September 2017, we exercised the option to license Validive from Onxeo for $1 million. In March 2023, we discontinued our Validive Phase 2b/3 VOICE trial based upon ours Data Safety Monitoring Board’s determination that the trial did not meet the pre-defined threshold for efficacy of a 15% absolute difference in severe oral mucositis prevention between Validive and placebo.
Removed
The fifth dose level is over twice the highest dose administered in any prior camsirubicin clinical trial (650 mg/m 2 versus 265 mg/m 2 ) and no drug-related cardiotoxicity has been observed to date up to the current dose-level. The open-label Phase 1b camsirubicin dose-escalation trial is planning to enroll additional cohorts until the maximum tolerable dose is reached.
Removed
In November 2022, we presented an abstract and poster of the Phase 1b clinical trial data at the Connective Tissue Oncology Society Annual Meeting in Vancouver, BC.
Removed
Following completion of the Phase 1b clinical trial, we continue to expect that Grupo Español de Investigación en Sarcomas (“GEIS”) will sponsor and lead a multi-country, randomized, open-label Phase 2 clinical trial to evaluate camsirubicin head-to-head against doxorubicin, the current first-line treatment for ASTS.

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