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What changed in Marker Therapeutics, Inc.'s 10-K — 2022 vs 2023

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Paragraph-level year-over-year comparison of Marker Therapeutics, Inc.'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.

+413 added−441 removedSource: 10-K (2023-12-31) vs 10-K (2022-12-31)

Top changes in Marker Therapeutics, Inc.'s 2023 10-K

413 paragraphs added · 441 removed · 289 edited across 6 sections

Item 1. Business

Business — how the company describes what it does

88 edited+35 added−79 removed192 unchanged
Biggest changeWe are advancing three product candidates as part of our multiTAA-specific T cell program for: 1. autologous treatment of lymphoma, and selected solid tumors 2. allogeneic T cells for the treatment of AML 3. off-the-shelf products in various indications We do not genetically engineer our multiTAA-specific T cell therapies and we believe that our product candidates are superior to T cells engineered with chimeric antigen receptors, or CAR-T, for several reasons including: ● Multiple targets → enhanced tumoricidal effect→ minimized tumor immune escape ● Epitope spreading → broad patient T cell expansion → durable endogenous antitumor immune response ● Clinical safety → no reported cytokine release syndrome (CRS) or other severe adverse effects (SAEs) in our clinical trials to date ● Standard IV administration → outpatient treatment → enhanced accessibility ● Non-engineered → reduced manufacturing complexity → lower cost 1 Table of Contents For these reasons, we believe our endogenous T cell receptor-based therapies may provide meaningful clinical benefit and safety to patients with both liquid and solid tumors.
Biggest changeWe are advancing two product candidates for 3 clinical indications as part of our multiTAA-specific T cell program for: ● Autologous multiTAA product for the treatment of lymphoma and pancreatic cancer (MT-601) ● Off-the-Shelf (OTS) product in various indications (e.g., MT-401-OTS) We do not genetically engineer our multiTAA-specific T cell therapies and we believe that our product candidates are superior to T cells engineered with chimeric antigen receptors, or CAR-T, for several reasons including: ● Multiple targets → enhanced tumoricidal effect→ minimized tumor immune escape ● Clinical safety → no treatment-related side effects, including cytokine release syndrome (CRS) or other severe adverse effects (SAEs), were attributed to the use of multiTAA-specific T cell therapies to date ● Non-genetically engineered T cell products → selective expansion of tumor-specific T cells from a patient’s or donor’s blood capable of recognizing a broad range of tumor antigens → no risk of mutagenesis and reduced manufacturing complexity → lower cost ​ For these reasons, we believe our endogenous T cell receptor-based therapies may provide meaningful clinical benefit and safety to patients with both hematological and solid tumors. 1 Table of Contents We believe that the simplicity of our manufacturing process allows additional modifications to expand multiTAA-specific T cell recognition of cancer targets.
Competition may also arise from: ● other drug development technologies and methods of preventing or reducing the incidence of disease; ● new small molecules; or ● other classes of therapeutic agents.
Competition may also arise from: ● other drug development technologies and methods of preventing or reducing the incidence of disease; ● new small molecules; and/ or ● other classes of therapeutic agents.
We face, and will continue to face, intense competition from other companies for collaborative arrangements with pharmaceutical and biotechnology companies, for establishing relationships with academic and research institutions and for licenses to drug candidates or proprietary technology. These competitors, either alone or with their collaborative partners, may succeed in developing products that are more effective than ours.
We face, and will continue to face, competition from other companies for collaborative arrangements with pharmaceutical and biotechnology companies, for establishing relationships with academic and research institutions and for licenses to drug candidates or proprietary technology. These competitors, either alone or with their collaborative partners, may succeed in developing products that are more effective than ours.
When infused into a cancer patient, the multiTAA-specific T cells are designed to kill cancer cells expressing the TAA and potentially recruit the patient’s immune system to participate in the cancer killing process. We licensed the underlying technology for multiTAA-specific T cell therapy from Baylor College of Medicine, or BCM, in March 2018.
When infused into a patient with cancer, the multiTAA-specific T cells are designed to kill cancer cells expressing the TAA and potentially recruit the patient’s immune system to participate in the cancer killing process. We licensed the underlying technology for multiTAA-specific T cell therapy from Baylor College of Medicine, or BCM, in March 2018.
In addition, upon a liquidity event (as defined in the BCM License Agreement) of the Company, BCM will receive a liquidity incentive payment of 0.5% of the liquidity event proceeds (as defined in the BCM License Agreement). 21 Table of Contents We have agreed to indemnify BCM and certain persons affiliated with BCM against claims and liabilities directly or indirectly related to or arising out of the design, process, manufacture or use by any third party of the licensed products, even though such claims and liabilities result in whole or in part from the negligence of the BCM indemnified parties or are based upon doctrines of strict liability or product liability, but not claims or liabilities arising from the gross negligence or intentional misconduct of any such BCM indemnified parties.
In addition, upon a liquidity event (as defined in the BCM License Agreement) of the Company, BCM will receive a liquidity incentive payment of 0.5% of the liquidity event proceeds (as defined in the BCM License Agreement). 15 Table of Contents We have agreed to indemnify BCM and certain persons affiliated with BCM against claims and liabilities directly or indirectly related to or arising out of the design, process, manufacture or use by any third party of the licensed products, even though such claims and liabilities result in whole or in part from the negligence of the BCM indemnified parties or are based upon doctrines of strict liability or product liability, but not claims or liabilities arising from the gross negligence or intentional misconduct of any such BCM indemnified parties.
Fast track designation, breakthrough therapy designation, priority review, accelerated approval, and RMAT designation do not change the standards for approval but may expedite the development or approval process. 28 Table of Contents Orphan Drug Designation Under the Orphan Drug Act, the FDA may grant orphan designation to a drug or biologic intended to treat a rare disease or condition, which is a disease or condition that affects fewer than 200,000 individuals in the United States, or more than 200,000 individuals in the United States for which there is no reasonable expectation that the cost of developing and making available in the United States a drug or biologic for this type of disease or condition will be recovered from sales in the United States for that drug or biologic.
Fast track designation, breakthrough therapy designation, priority review, accelerated approval, and RMAT designation do not change the standards for approval but may expedite the development or approval process. 22 Table of Contents Orphan Drug Designation Under the Orphan Drug Act, the FDA may grant orphan designation to a drug or biologic intended to treat a rare disease or condition, which is a disease or condition that affects fewer than 200,000 individuals in the United States, or more than 200,000 individuals in the United States for which there is no reasonable expectation that the cost of developing and making available in the United States a drug or biologic for this type of disease or condition will be recovered from sales in the United States for that drug or biologic.
The effect of patent expiration on our product candidates also depends upon many other factors such as the nature of the market and the position of the product in it, the growth of the market, the complexities and economics of the process for manufacture of the active ingredient of the product and the requirements of new drug provisions of the Federal Food, Drug and Cosmetic Act or similar laws and regulations in other countries. 23 Table of Contents Our pending patent applications cover a range of technologies, including specific embodiments and applications for treatment of various medical indications, improved application methods and adjunctive utilization with other therapeutic modalities.
The effect of patent expiration on our product candidates also depends upon many other factors such as the nature of the market and the position of the product in it, the growth of the market, the complexities and economics of the process for manufacture of the active ingredient of the product and the requirements of new drug provisions of the Federal Food, Drug and Cosmetic Act or similar laws and regulations in other countries. 17 Table of Contents Our pending patent applications cover a range of technologies, including specific embodiments and applications for treatment of various medical indications, improved application methods and adjunctive utilization with other therapeutic modalities.
Additionally, appropriate packaging must be selected and tested, and stability studies must be conducted to demonstrate that the product candidate does not undergo unacceptable deterioration over its shelf life. 26 Table of Contents BLA Submission and Review Assuming successful completion of all required testing in accordance with all applicable regulatory requirements, the results of product development, nonclinical studies and clinical trials are submitted to the FDA as part of a BLA requesting approval to market the product for one or more indications.
Additionally, appropriate packaging must be selected and tested, and stability studies must be conducted to demonstrate that the product candidate does not undergo unacceptable deterioration over its shelf life. 20 Table of Contents BLA Submission and Review Assuming successful completion of all required testing in accordance with all applicable regulatory requirements, the results of product development, nonclinical studies and clinical trials are submitted to the FDA as part of a BLA requesting approval to market the product for one or more indications.
Therapies targeting only a single antigen are vulnerable to evolutionary escape mechanisms. ​ ​ While single-antigen specific therapy can eliminate all the tumor cells expressing the targeted antigen, the residual tumor cells that do not express that antigen may survive and expand.
Therapies targeting only a single antigen are vulnerable to evolutionary escape mechanisms. ​ ​ While single-antigen specific therapies can eliminate all the tumor cells expressing the targeted antigen, the residual tumor cells that do not express that antigen may survive and expand.
In May 2020, we reported interim data from an ongoing Phase 1/2 clinical trial of the multiTAA-specific T cell therapy for the treatment of pancreatic adenocarcinoma being conducted by BCM.
Pancreatic Cancer In May 2020, we reported interim data from an ongoing Phase 1/2 clinical trial of the multiTAA-specific T cell therapy for the treatment of pancreatic adenocarcinoma being conducted by BCM.
Other potential consequences include, among other things: ● restrictions on the marketing or manufacturing of a product, complete withdrawal of the product from the market or product recalls; ● fines, warning letters or holds on post-approval clinical studies; ● refusal of the FDA to approve pending applications or supplements to approved applications, or suspension or revocation of existing product approvals; ● product seizure or detention, or refusal of the FDA to permit the import or export of products; or 29 Table of Contents ● injunctions or the imposition of civil or criminal penalties.
Other potential consequences include, among other things: ● restrictions on the marketing or manufacturing of a product, complete withdrawal of the product from the market or product recalls; ● fines, warning letters or holds on post-approval clinical studies; ● refusal of the FDA to approve pending applications or supplements to approved applications, or suspension or revocation of existing product approvals; ● product seizure or detention, or refusal of the FDA to permit the import or export of products; or 23 Table of Contents ● injunctions or the imposition of civil or criminal penalties.
Our ability to compete successfully will depend, in part, on our ability to: ● develop proprietary products; ● develop and maintain products that reach the market first, are technologically superior to and/or are of lower cost than other products in the market; ● attract and retain scientific, product development and sales and marketing personnel; 20 Table of Contents ● obtain patent or other proprietary protection for our products and technologies; ● obtain required regulatory approvals; and ● manufacture, market, distribute and sell any products that we develop.
Our ability to compete successfully will depend, in part, on our ability to: ● develop proprietary products; ● develop and maintain products that reach the market first, are technologically superior to and/or are of lower cost than other products in the market; ● attract and retain scientific, product development and sales and marketing personnel; 14 Table of Contents ● obtain patent or other proprietary protection for our products and technologies; ● obtain required regulatory approvals; and ● manufacture, market, distribute and sell any products that we develop.
While CAR-T and TCR therapies generally target a single epitope, our manufacturing process selects for T cells that are specific for multiple peptides derived from several targeted antigens. Deep gene sequencing of our products shows that a typical patient dose usually consists of approximately 4,000 unique T cell clonotypes, some of which target up to five different tumor-associated antigens.
While CAR-T and TCR therapies generally target a single epitope, our manufacturing process selects for T cells that are specific for multiple peptides derived from several targeted antigens. Deep gene sequencing of our products shows that a typical patient dose usually consists of approximately 4,000 unique T cell clonotypes, some of which target up to six different tumor-associated antigens.
This overlapping structure allows us to isolate, activate and expand any T cell that is specific for any segment of the antigens that we target in the unique genetic background of every patient. 18 Table of Contents The G-Rex is a cell culture device manufactured by Wilson Wolf Manufacturing Corporation, or Wilson Wolf, used by many cell therapy developers, both in commercial and academic settings.
This overlapping structure allows us to isolate, activate and expand any T cell that is specific for any segment of the antigens that we target in the unique genetic background of every patient. 12 Table of Contents The G-Rex is a cell culture device manufactured by Wilson Wolf Manufacturing Corporation, or Wilson Wolf, used by many cell therapy developers, both in commercial and academic settings.
Additionally, separate reimbursement for the product itself or the treatment or procedure in which the product is used may not be available, which may impact physician utilization. 31 Table of Contents In addition, the U.S. government, state legislatures and foreign governments have continued implementing cost-containment programs, including price controls, restrictions on coverage and reimbursement and requirements for substitution of generic products.
Additionally, separate reimbursement for the product itself or the treatment or procedure in which the product is used may not be available, which may impact physician utilization. 25 Table of Contents In addition, the U.S. government, state legislatures and foreign governments have continued implementing cost-containment programs, including price controls, restrictions on coverage and reimbursement and requirements for substitution of generic products.
By November 2022, all six patients had completed dose-limiting toxicity (DLT) periods with no DLTs reported. ● In the fourth quarter of 2021, the manufacturing of MT-401 for the Phase 2 trial started at the Marker Cell Therapy cGMP manufacturing facility, named MCTF01. The Company transitioned to treating patients using MT-401 manufactured with Marker’s new T cell manufacturing process.
By November 2022, all six patients had completed dose-limiting toxicity (DLT) periods with no DLTs reported. ● In the fourth quarter of 2021, the manufacturing of MT-401 for the Phase 2 trial started at the Marker Cell Therapy cGMP manufacturing facility, named MCTF01. We transitioned to treating patients using MT-401 manufactured with Marker’s new T cell manufacturing process.
With respect to both licensed and company-owned intellectual property, we cannot be sure that patents will be granted with respect to any of our pending patent applications or with respect to any patent applications filed in the future, nor can we be sure that any of our existing 22 Table of Contents patents or any patents that may be granted in the future will be commercially useful in protecting our commercial products and methods of manufacturing the same.
With respect to both licensed and company-owned intellectual property, we cannot be sure that patents will be granted with respect to any of our pending patent applications or with respect to any patent applications filed in the future, nor can we be sure that any of our existing 16 Table of Contents patents or any patents that may be granted in the future will be commercially useful in protecting our commercial products and methods of manufacturing the same.
The FDA may require one or more Phase 4 post-market studies and surveillance to further assess and monitor the product’s safety and effectiveness after commercialization and may limit further marketing of the product based on the results of these post-marketing studies. 27 Table of Contents Expedited Development and Review Programs The FDA offers a number of expedited development and review programs for qualifying product candidates.
The FDA may require one or more Phase 4 post-market studies and surveillance to further assess and monitor the product’s safety and effectiveness after commercialization and may limit further marketing of the product based on the results of these post-marketing studies. 21 Table of Contents Expedited Development and Review Programs The FDA offers a number of expedited development and review programs for qualifying product candidates.
As a result, the ultimate impact, implementation, and impact of the BPCIA is subject to significant uncertainty. 30 Table of Contents Other Healthcare Laws and Compliance Requirements Pharmaceutical companies are subject to additional healthcare regulation and enforcement by the federal government and by authorities in the states and foreign jurisdictions in which they conduct their business.
As a result, the ultimate impact, implementation, and impact of the BPCIA is subject to significant uncertainty. 24 Table of Contents Other Healthcare Laws and Compliance Requirements Pharmaceutical companies are subject to additional healthcare regulation and enforcement by the federal government and by authorities in the states and foreign jurisdictions in which they conduct their business.
The ARTEMIS trial conducted by Marker has completed in June 2021 the safety lead-in portion, which tested the comparability of MT-401 or zedenoleucel, the multiTAA-specific T cell product manufactured using peptides from two different vendors and enrolled six patients with active disease: one measurable residual disease (MRD) positive patient and five frank relapse patients. ● Consistent with the results of the BCM Phase 1 trial, there were no dose-limiting toxicities, cytokine release syndrome or neurotoxicity observed in this stage of the trial, and one MRD+ patient became MRD- after infusion of MT-401.
In 2021, the ARTEMIS trial conducted by Marker has completed the safety lead-in portion, which tested the comparability of MT-401 or zedenoleucel, the multiTAA-specific T cell product manufactured using peptides from two different vendors and enrolled six patients with active disease: one measurable residual disease (MRD) positive patient and five frank relapse patients. ● Consistent with the results of the BCM Phase 1 trial, there were no dose-limiting toxicities, cytokine release syndrome or neurotoxicity observed in this stage of the trial\.
The five-year mortality rate for patients who receive an allogeneic HSCT exceeds 50%, and patients who relapse after a transplant have a survival expectation of approximately 4.5 months. 10 Table of Contents BCM recently completed a Phase 1 AML/MDS clinical trial of the multiTAA-specific T cell therapy for the treatment of patients with post-transplant AML.
The five-year mortality rate for patients who receive an allogeneic HSCT exceeds 50%, and patients who relapse after a transplant have a survival expectation of approximately 4.5 months. BCM recently completed a Phase 1 AML/MDS clinical trial of the multiTAA-specific T cell therapy for the treatment of patients with post-transplant AML.
As a result, the FDA concurrently released a final rule and guidance in September 2020 providing pathways for states to build and submit importation 32 Table of Contents plans for drugs from Canada.
As a result, the FDA concurrently released a final rule and guidance in September 2020 providing pathways for states to build and submit importation 26 Table of Contents plans for drugs from Canada.
There can be no assurance that liability claims will not exceed such insurance coverage limits, which could have a materially adverse effect on our business, financial condition or results of operations or that such insurance will continue to be available on commercially reasonable terms, if at all. Human Resources Employees As of December 31, 2022, we had 67 full-time employees.
There can be no assurance that liability claims will not exceed such insurance coverage limits, which could have a materially adverse effect on our business, financial condition or results of operations or that such insurance will continue to be available on commercially reasonable terms, if at all. Human Resources Employees As of December 31, 2023, we had 8 full-time employees.
We are developing a portfolio of highly differentiated T cell therapies utilizing the 5 Table of Contents multiTAA-specific T cell platform that we believe has the potential to significantly disrupt the current cell therapy landscape, while substantially improving survival and quality of life for patients with cancers.
We are developing a portfolio of highly differentiated T cell therapies utilizing the multiTAA-specific T cell platform that we believe has the potential to significantly disrupt the current cell therapy landscape, while substantially improving survival and quality of life for patients with cancers.
No cytokine release syndrome or neurotoxicity has been observed in any arm of the trial to date. 12 Table of Contents Arm A Arm A is designed to evaluate the safety and potential efficacy of using multiTAA-specific T cell therapy as part of first-line treatment for patients with pancreatic cancer.
No cytokine release syndrome or neurotoxicity has been observed in any arm of the trial to date. ​ 9 Table of Contents Arm A was designed to evaluate the safety and potential efficacy of using multiTAA-specific T cell therapy as part of first-line treatment for patients with pancreatic cancer.
In those studies, BCM saw evidence of clinical benefit, expansion of infused cells epitope spreading, and decreased toxicity compared to other cellular therapies.
In those studies, BCM saw evidence of clinical benefit, expansion of infused cells, and decreased toxicity compared to other cellular therapies.
The improved manufacturing process enables products with increased antigen specificity and diversity, both of which have a strong linear correlation to anti-tumor activity and four-fold increase in potency in vitro. · Invest in our platform to maximize the beneficial outcomes for cancer patients.
We believe the improved manufacturing process enables products with increased antigen specificity and diversity, both of which have a strong linear correlation to anti-tumor activity and has resulted in a four-fold increase in potency in vitro. ​ · Invest in our platform to maximize the beneficial outcomes for cancer patients.
Our consultants may be employed by other entities and therefore may have commitments to their employer or may have other consulting or advisory agreements that may limit their availability to us. 33 Table of Contents Human Capital Resources Our human capital resources objectives include, as applicable, identifying, recruiting, retaining, incentivizing and integrating our existing and additional employees.
Our consultants may be employed by other entities and therefore may have commitments to their employer or may have other consulting or advisory agreements that may limit their availability to us. Human Capital Resources Our human capital resources objectives include, as applicable, identifying, recruiting, retaining, incentivizing and integrating our existing and additional employees.
None of the patients in CR had relapsed, and the range for the duration of CR in these patients were between two and over five years after being infused with the multiTAA-specific T cell therapy with the exception of one CR patient who died of an unrelated pneumonia.
None of the patients in CR had relapsed, and the range for the duration of CR in these patients was between two and over five years after being infused with the multiTAA-specific T cell therapy with the exception of one patient who died of an unrelated pneumonia while in a CR.
The five antigen targets can be recognized by a very wide range of T cells, which we believe facilitates robust killing of targeted cancer cells. Clinical Development of Our multiTAA-Specific T Cell Therapies by BCM The following clinical trials are being conducted by BCM pursuant to our strategic alliance.
The six antigen targets can be recognized by a very wide range of T cells, which we believe facilitates robust killing of targeted cancer cells. Clinical Development of Our multiTAA-Specific T Cell Therapies by BCM The following clinical trials were conducted by BCM pursuant to our strategic alliance.
The process required by the FDA before biologic product candidates may be marketed in the United States generally involves the following: ● completion of preclinical laboratory tests and animal studies performed in accordance with the FDA’s current Good Laboratory Practices, or GLP, regulation; ● submission to the FDA of an IND, which must become effective before clinical trials may begin and must be updated annually or when significant changes are made; ● approval by an independent Institutional Review Board, or IRB, or ethics committee at each clinical site before the trial is commenced; ● performance of adequate and well-controlled human clinical trials to establish the safety, purity and potency of the proposed biologic product candidate for its intended purpose; ● preparation of and submission to the FDA of a biologics license application, or BLA, after completion of all pivotal clinical trials; ● a determination by the FDA within 60 days of its receipt of a BLA to file the application for review; ● satisfactory completion of an FDA Advisory Committee review, if applicable; ● satisfactory completion of an FDA pre-approval inspection of the manufacturing facility or facilities at which the proposed product is produced to assess compliance with cGMP and to assure that the facilities, methods and controls are adequate to preserve the biological product’s continued safety, purity and potency, and of selected clinical investigation sites to assess compliance with Good Clinical Practices, or GCP; and ● FDA review and approval of the BLA to permit commercial marketing of the product for particular indications for use in the United States. 25 Table of Contents Preclinical and Clinical Development Prior to beginning the first clinical trial with a product candidate, we must submit an IND to the FDA.
We, along with third-party contractors, will be required to navigate the various preclinical, clinical and commercial approval requirements of the governing regulatory agencies of the countries in which we wish to conduct studies or seek approval or licensure of our product candidates. 18 Table of Contents The process required by the FDA before biologic product candidates may be marketed in the United States generally involves the following: ● completion of preclinical laboratory tests and animal studies performed in accordance with the FDA’s current Good Laboratory Practices, or GLP, regulation; ● submission to the FDA of an IND, which must become effective before clinical trials may begin and must be updated annually or when significant changes are made; ● approval by an independent Institutional Review Board, or IRB, or ethics committee at each clinical site before the trial is commenced; ● performance of adequate and well-controlled human clinical trials to establish the safety, purity and potency of the proposed biologic product candidate for its intended purpose; ● preparation of and submission to the FDA of a biologics license application, or BLA, after completion of all pivotal clinical trials; ● a determination by the FDA within 60 days of its receipt of a BLA to file the application for review; ● satisfactory completion of an FDA Advisory Committee review, if applicable; ● satisfactory completion of an FDA pre-approval inspection of the manufacturing facility or facilities at which the proposed product is produced to assess compliance with cGMP and to assure that the facilities, methods and controls are adequate to preserve the biological product’s continued safety, purity and potency, and of selected clinical investigation sites to assess compliance with Good Clinical Practices, or GCP; and ● FDA review and approval of the BLA to permit commercial marketing of the product for particular indications for use in the United States. 19 Table of Contents Preclinical and Clinical Development Prior to beginning the first clinical trial with a product candidate, we must submit an IND to the FDA.
For instance, we optimized the multiTAA-specific T cell manufacturing process by closing the system and reducing the total manufacturing time from the original 36 days (BCM) to nine days. The improved manufacturing process has been implemented to supply all of the clinical products used in our current company-sponsored Phase 1 and Phase 2 trials.
We previously optimized the multiTAA-specific T cell manufacturing process by closing the system and reducing the total manufacturing time from the original 36 days (BCM) to nine days. The improved manufacturing process has been implemented to supply all of the clinical products used in our current company-sponsored clinical trials.
This system allows for the highly robust growth of cells in culture, by providing them with superior access to oxygen and nutrients. Cells manufactured in the device grow efficiently without need for agitation by a technician, scientist or automated system. Inside the G-Rex, PBMCs are co-cultured with antigen-presenting cells that have been exposed to the stimulating peptide pools.
This system allows for the highly robust growth of cells in culture, by providing them with superior access to oxygen and nutrients. Cells manufactured in the device grow efficiently without need for agitation by a technician, scientist or automated system. Inside the G-Rex, PBMCs, including T cells and antigen-presenting cells, are exposed to the stimulating peptide pools.
Responses in all six patients who entered CR were associated with an expansion of infused T cells, as well as induction of broad-based antigen spreading across many tumor-associated antigens. ​ ​ 16 Table of Contents We also treated 17 patients, including one patient who was treated a second time after a relapse, in remission, which we refer to as the adjuvant lymphoma group.
Responses in all six patients who entered CR were associated with an expansion of infused T cells, as well as induction of broad-based antigen spreading across many tumor-associated antigens. ​ ​ 11 Table of Contents BCM also treated 17 patients, including one patient who was treated a second time after a relapse, in remission (adjuvant lymphoma group).
In the adjuvant setting, patients will be randomized to either multiTAA-specific T cell therapy or standard of care (observation) at approximately 90 days post-transplant, while the active disease patients will receive MT-401 following relapse post-transplant as part of a single-arm group. ● In April 2020, the Orphan Product Development Office of the United States Food and Drug Administration, or the FDA, granted orphan drug designation to MT-401 (zedenoleucel), a multiTAA-specific T cell therapy that targets four TAAs, for the treatment of AML. ● The same multiTAA-specific T cell therapy has been well tolerated in an ongoing Phase 1 clinical trial in AML and myelodysplastic syndrome, or MDS, conducted by our strategic partner Baylor College of Medicine, or BCM. ● As reported in a 2021 publication by Lulla et al., 11 of the 17 patients in the adjuvant disease setting dosed with the multiTAA-specific T cell therapy after receiving an allogeneic hematopoietic stem cell transplant, or HSCT, never relapsed [median leukemia-free survival, or LFS, not reached at a median follow-up of 1.9 years], with 11 of 15 patients (two patients were each treated during two different remissions) remaining alive (estimated two-year overall survival of 77%) at a median follow-up of 2 Table of Contents 1.9 years post-infusion, which compares favorably with HSCT outcomes for risk-matched AML/MDS patients post-HSCT [median LFS of nine to 15 months and two-year survival probability of 42%]. ● Additionally, eight patients were treated for active disease that was resistant to salvage therapy post-HSCT with a median of five prior lines of therapy (range: four to 10). o One of the eight patients crossed over from the adjuvant group, while two patients enrolled twice, but all three patients had active AML that failed another line of salvage therapy after their first multiTAA-specific T cell infusion. o Two of the eight patients achieved objective responses, with one complete response and one partial response, with six patients continuing with stable disease. o We have observed evidence of a patient’s natural immune system participating in cancer killing (epitope spreading) after infusion of our multiTAA-specific T cell therapy.
The dose administered in this multicenter trial was up to 200 million cells every two weeks for up to three doses. ● In April 2020, the Orphan Product Development Office of the United States Food and Drug Administration, or the FDA, granted orphan drug designation to MT-401 (zedenoleucel), a multiTAA-specific T cell therapy that targets four TAAs, for the treatment of AML. ● The same multiTAA-specific T cell therapy has been well tolerated in an ongoing Phase 1 clinical trial in AML and myelodysplastic syndrome, or MDS, conducted by our strategic partner Baylor College of Medicine, or BCM. 2 Table of Contents ● As reported in a 2021 publication by Lulla et al., 11 of the 17 patients in the adjuvant disease setting dosed with the multiTAA-specific T cell therapy after receiving an allogeneic HSCT were relapse free [median leukemia-free survival, or LFS, not reached at a median follow-up of 1.9 years], with 11 of 15 patients (two patients were each treated during two different remissions) remaining alive (estimated two-year overall survival of 77%) at a median follow-up of 1.9 years post-infusion, which compares favorably with HSCT outcomes for risk-matched AML/MDS patients post-HSCT [median LFS of nine to 15 months and two-year survival probability of 42%]. ● Additionally, eight patients were treated for active disease that was resistant to salvage therapy post-HSCT with a median of five prior lines of therapy (range: four to 10). o One of the eight patients crossed over from the adjuvant group, while two patients enrolled twice, but all three patients had active AML that failed another line of salvage therapy after their first multiTAA-specific T cell infusion. o Two of the eight patients achieved objective responses, with one complete response and one partial response, with six patients continuing with stable disease. o We have observed evidence of a patient’s natural immune system participating in cancer killing (epitope spreading) after infusion of our multiTAA-specific T cell therapy.
Trademarks We currently have pending with the USPTO applications for registration of the trademarks POLYSTART and “Marker Therapeutics.” We currently have the trademark “TapImmune” registered with the USPTO. We also have rights to use other names essential to our business.
Trademarks We currently have pending with the USPTO applications for registration of the trademarks “Marker Therapeutics.” We also have rights to use other names essential to our business.
As shown below, two of the eight patients achieved objective responses with one complete response and one partial response, with six patients continuing with stable disease. ​ ​ In this trial, the multiTAA-specific T cell therapy was well tolerated, with no drug-related serious adverse events and no instances of greater than Grade 2 graft-versus-host disease.
Two of the eight patients achieved objective responses with one complete response and one partial response, with six patients continuing with stable disease. ​ In this trial, the multiTAA-specific T cell therapy was well tolerated, with no drug-related serious adverse events and no instances of greater than Grade 2 acute graft-versus-host disease or moderate-severe chronic GVHD.
We have patents and patent applications in other countries, as well as in the European Patent Office, that we believe provide equivalent or comparable protection for our product candidates in jurisdictions internationally that we consider to be key markets. Patent applications related to our PolyStart technology are pending in Brazil and Canada.
We have patents and patent applications in other countries, as well as in the European Patent Office, that we believe provide equivalent or comparable protection for our product candidates in jurisdictions internationally that we consider to be key markets.
In addition, tumor cells may also downregulate or mutate the targeted antigen, thus becoming invisible to the T cell therapy. Both phenomena create a transformed tumor that is impervious to that therapy.
In addition, tumor cells may also downregulate or mutate the targeted antigen, thus becoming invisible to the T cell therapy. Both phenomena create a transformed tumor that is impervious to that therapy. This process is referred to as antigen-negative tumor escape.
In addition, libraries of overlapping peptides, which we refer to as peptide pools, spanning the target antigens are combined with antigen presenting cells and added to the cell culture. Each peptide within a peptide pool represents a small segment of a target antigen, which a T cell might recognize.
In addition, libraries of overlapping peptides, which we refer to as peptide pools, are added to the cell culture. Each peptide within a peptide pool represents a small segment of a target antigen, which a T cell might recognize.
We believe that our non-engineered T cells therapy and our in vivo T-cell therapy approaches will be synergistic and may improve therapies being developed by these competitors.
We believe that our non-engineered T cell therapy approaches will be synergistic and may improve therapies being developed by potential competitors.
Correlative studies showed that the patient saw significant expansion of infused multiTAA-specific T cells in addition to extensive epitope spreading. There were no objective responses from the frank relapse patients.
Correlative studies showed that the patient saw significant expansion of infused multiTAA-specific T cells. There were no objective responses from the frank relapse patients.
Group 1 will comprise of 150 adjuvant (disease-free) patients, with the primary endpoint of relapse-free survival of patients randomized to receive MT-401 versus a control group. Group 2 will comprise of 60 active disease patients in a single arm, with primary endpoints of complete remission and duration of complete remission.
Group 1 comprised adjuvant (disease-free) patients, with the primary endpoint of relapse-free survival of patients randomized to receive MT-401 versus a control group. Group 2 comprised active disease patients in 2 single arm cohorts (MRD+ only and active disease), with primary endpoints of complete remission and duration of complete remission.
Cancers are heterogeneous in their expression of antigens. Tumors generally consist of individual cancer cells expressing different antigens, and each of those antigens can be present at a different level that can change over time.
Tumors generally consist of individual cancer cells expressing different antigens, and each of those antigens can be present at a different level that can change over time.
The FDA cleared the Company’s IND application for MT-601 in November 2022 to initiate the PANACEA study, a Phase 1 multicenter clinical trial in locally advanced, unresectable or metastatic pancreatic cancer to assess the safety and efficacy of MT-601 in combination with front-line chemotherapy.
The FDA cleared our IND application for MT-601 in November 2022 to initiate the PANACEA study, a Phase 1 multicenter clinical trial in locally advanced, unresectable or metastatic pancreatic cancer to assess the safety and efficacy of MT-601 in combination with front-line chemotherapy. The PANACEA trial will include a dose escalation portion followed by a dose expansion portion.
This leads to a more effective treatment platform with fewer side effects. Some of these infused T cells may remain in the body for long periods, providing immunological memory, thus leading to longer and more durable responses. TCRs and CARs have distinct signaling properties and antigen sensitivities.
Some of these infused T cells may remain in the body for long periods, providing immunological memory, thus leading to longer and more durable responses. TCRs and CARs have distinct signaling properties and antigen sensitivities.
As reported in a 2021 publication by Lulla et al. and illustrated below, 11 of the 17 patients in the adjuvant disease setting dosed with the multiTAA-specific T cell therapy after receiving an allogeneic HSCT never relapsed [median LFS not reached at a median follow-up of 1.9 years], with 11 of 15 patients (two patients were each treated during two different remissions) remaining alive (estimated two-year overall survival of 77%) at a median follow-up of 1.9 years post-infusion which compares favorably with HSCT outcomes for risk-matched AML/MDS patients post-HSCT [median LFS of nine to 15 months and two-year survival probability of 42%]. ​ ​ 11 Table of Contents Additionally, eight patients were treated for active disease that was resistant to salvage therapy post-HSCT with a median of five prior lines of therapy (range: four to ten).
As reported in a 2021 publication by Lulla et al., 11 of the 17 patients in the adjuvant disease setting dosed with the multiTAA-specific T cell therapy after receiving an allogeneic HSCT did not relapse during the follow-up period of the study [median LFS not reached at a median follow-up of 1.9 years], with 11 of 15 patients (two patients were each treated during two different remissions) remaining alive (estimated two-year overall survival of 77%) at a median follow-up of 1.9 years post-infusion which compares favorably with HSCT outcomes for risk-matched AML/MDS patients post-HSCT [median LFS of nine to 15 months and two-year survival probability of 42%].
Specifically, the new process involves an improved T cell manufacturing process for MT-401 that reduces production time to 9 days (compared to the original process of >30 days).
The improved manufacturing process greatly reduced the manufacturing time and increased both the antigen specificity and diversity. Specifically, the new process involves an improved T cell manufacturing process for MT-401 that reduces production time to 9 days (compared to the original process of >30 days).
There were 54 in research, development, quality, CMC and clinical and 13 were in finance, legal, human resources or administrative support. None of our employees is subject to a collective bargaining agreement. We consider our relationship with our employees to be good. Consultants We have consulting agreements with a number of leading academic scientists, clinicians and regulatory experts.
There were 6 in clinical and 2 were in administrative support. None of our employees is subject to a collective bargaining agreement. We consider our relationship with our employees to be good. Consultants We have consulting agreements with a number of leading academic scientists, clinicians and regulatory experts.
We developed our lead product candidates from our multiTAA-specific T cell technology, which is based on the manufacture of non-engineered, tumor-specific T cells that recognize multiple tumor associated antigens, or TAAs. MultiTAA-specific T cells are able to recognize multiple tumor targets to produce broad spectrum anti-tumor activity.
We developed our lead product candidates from our multi tumor associated antigen (“multiTAA”)-specific T cell technology, which is based on the manufacture of non-engineered, tumor-specific T cells that recognize multiple tumor-associated antigens, or TAAs. This approach selectively expands tumor-specific T cells from a patient’s/donor’s blood and is able to recognize multiple tumor targets to produce broad spectrum anti-tumor activity.
After discontinuing treatment and receiving decitabine, the patient relapsed and later re-enrolled in the trial in the active disease group and entered CR for 13 months and survived for 2.5 years. Pancreatic Cancer We are developing MT-601 for the treatment of advanced unresectable pancreatic cancer.
After discontinuing treatment and receiving decitabine, the patient relapsed and later re-enrolled in the trial in the active disease group and entered CR for 13 months and survived for 2.5 years.
A total of 31 patients were administered the multiTAA-specific T cell therapy: 13 patients in Arm A, 10 patients in Arm B and eight patients in Arm C. Overall, we have observed a clinical benefit correlated with the detection of tumor-reactive T cells in patient peripheral blood (Arms A, B and C) and within tumor biopsy samples (Arm C) post-infusion.
Overall, we have observed a clinical benefit correlated with the detection of tumor-reactive T cells in patient peripheral blood (Arms A, B and C) and within tumor biopsy samples (Arm C) post-infusion.
The MultiTAA-Specific T Cell Therapies In collaboration with BCM, we are advancing three multiTAA-specific T cell therapies through clinical development: · Autologous multiTAA-specific T cell therapies target the NY-ESO-1, PRAME, MAGE-A4, Survivin and SSX2 antigens.
The MultiTAA-Specific T Cell Therapies We are advancing two multiTAA-specific T cell therapies through clinical development: · Autologous multiTAA-specific T cell therapies – The autologous product targets the NY-ESO-1, PRAME, MAGE - A4, Survivin, WT1 and SSX2 antigens (MT-601).
There are also opportunities to obtain an extension of term for patents covering a product in certain jurisdictions, which adds further complexity to the determination of patent life.
There are also opportunities to obtain an extension of term for patents covering a product in certain jurisdictions, which adds further complexity to the determination of patent life. The effect of the issued United States patents is that they provide us with patent protection for the claims covered by the patents.
Process Development and Manufacturing of The MultiTAA-Specific T Cell Therapies In the manufacturing process, blood is drawn from either the individual patient (in the case of the autologous T cells) or from the allogeneic stem cell transplant donor (in the case of the allogeneic T cells).
Process Development and Manufacturing of the MultiTAA-Specific T Cell Therapies In the manufacturing process, blood is drawn from either the individual patient (in the case of the autologous T cells) or from a healthy donors/commercially available leukapheresis material (in the case of the OTS program).
For 12 of the 13 patients, sufficient cells for all six planned doses were generated; two doses were available for the remaining patient. ● Out of the 13 evaluable patients (best overall response): o four patients experienced objective responses after administration of multiTAA cells; o one patient experienced a radiographic complete response occurring at month nine after starting chemotherapy; o three patients experienced partial responses per RECIST occurring at six-nine months after starting chemotherapy; o six patients experienced stable disease; o one patient experienced a mixed response (some lesions increased in size and others decreased for a net zero change in size of tumor lesions); ● Patients had durable cancer control with nine of the 13 patients exceeding historical control of overall survival; ● Five patients enrolled in the study were not administered multiTAA-specific T cells, either because of disease progression (four patients) which made them ineligible for treatment, or because insufficient starting material from the patient was available for manufacturing (one patient); ● Evidence of epitope-spreading was observed in all responders, suggesting that the multiTAA T cell therapy triggered the recruitment of a broader endogenous immune system response for improved anti-tumor activity; and ● No infusion-related reactions, cytokine release syndrome or neurotoxicity was observed. ● In patients responding to therapy, significant expansion of the infused multiTAA-specific T cell therapy was observed, along with broad-based epitope spreading, with significant expansion of endogenous T cells specific for other tumor specific antigens.
These patients in the chemo-responsive arm have completed at least three months of standard-of-care chemotherapy (gemcitabine/nab-paclitaxel or FOLFIRINOX), which is the period during which a response to chemotherapy would typically occur, before receiving up to six administrations of multiTAA-specific T cell therapy in conjunction with chemotherapy. ● Out of the 13 evaluable patients (best overall response): o four patients experienced objective responses after administration of multiTAA-specific T cells; o one patient experienced a radiographic complete response occurring at month nine after starting chemotherapy; o three patients experienced partial responses per RECIST occurring at six-nine months after starting chemotherapy; o six patients experienced stable disease; o one patient experienced a mixed response. ● Patients had durable cancer control with nine of the 13 patients exceeding historical control of overall survival; ● Five patients enrolled in the study were not administered multiTAA-specific T cells, either because of disease progression (four patients) which made them ineligible for treatment, or because insufficient starting material from the patient was available for manufacturing (one patient); ● Evidence of epitope-spreading was observed in all responders, suggesting that the multiTAA-specific T cell therapy triggered the recruitment of a broader endogenous immune system response for improved anti-tumor activity; ● No infusion-related reactions, cytokine release syndrome or neurotoxicity was observed; In patients responding to therapy, significant expansion of the infused multiTAA-specific T cell therapy was observed. 10 Table of Contents Lymphoma BCM evaluated the multiTAA-specific T cell therapy (5 TAA product) in a Phase 1 clinical trial for the treatment of patients with lymphoma.
In this trial, BCM plans to enroll approximately 45 patients with advanced or borderline resectable pancreatic adenocarcinoma in three arms: Arm A, which includes patients with unresectable/metastatic disease who are responding to standard first-line chemotherapy; Arm B, which includes patients with progressive disease or therapy intolerance; and Arm C, which includes patients with surgically resectable disease.
In 2020, we reported that in this trial, BCM administered multiTAA-specific T cells to a total of 31 patients with advanced or borderline resectable pancreatic adenocarcinoma in three arms: 13 patients in Arm A, which included patients with unresectable/metastatic disease who were responding to standard first-line chemotherapy; 12 patients in Arm B, which included patients with progressive disease or therapy intolerance; and eight patients in Arm C, which includes patients with surgically resectable disease.
These patients were heavily pre-treated and, on average, had failed a median of five prior lines of therapy (range four to eight) for the HL patients and a median of three prior lines of therapy (range three to four) for the NHL patients.
These patients were heavily pre-treated and had failed a median of five prior lines of therapy (range four to eight) for the HL patients and a median of three prior lines of therapy (range three to four) for the NHL patients. As illustrated below, in the active lymphoma group, six patients entered CR and nine patients had experienced stable disease.
The principal purposes of our equity incentive plans are to attract, retain and motivate selected employees, consultants and directors through the granting of equity-based compensation awards. We strive to create a diverse environment, and our commitment to diversity, equity and inclusion begins with our leadership team of diverse backgrounds and experiences.
The principal purposes of our equity incentive plans are to attract, retain and motivate selected employees, consultants and directors through the granting of equity-based compensation awards.
In January 2022, the FDA granted orphan drug designation to MT-601 for the treatment of patients with pancreatic cancer.
To date, we have not observed any cytokine release syndrome or neurotoxicity in this trial. In January 2022, the FDA granted orphan drug designation to MT-601 for the treatment of patients with pancreatic cancer.
In contrast, newer immunotherapy treatments activate specific, potent immune cells, leading to improved safety and efficacy. Within the immunotherapy category, treatments have included vaccines, cytokine therapies, antibody therapies, and adoptive cell therapies. In 1996, Dr. Dana Leach, Dr. Matthew Krummel and Dr. James Allison reported that monoclonal antibodies, or mAbs, blocking CTLA-4 could treat tumors in animal models.
Cancer immunotherapy began with treatments that nonspecifically activated the immune system and had limited efficacy and/or significant toxicity. In contrast, newer immunotherapy treatments activate specific, potent immune cells, leading to improved safety and efficacy. Within the immunotherapy category, treatments have included vaccines, cytokine therapies, antibody therapies, and adoptive cell therapies. In 1996, Dr. Dana Leach, Dr. Matthew Krummel and Dr.
The duration of response ranged from approximately nine months to over five years. ​ ​ In both treatment groups, the multiTAA-specific T cell therapy was well tolerated, with no drug-related serious adverse events, suggesting that the multiTAA-specific T cell therapy might serve as a standard-of-care maintenance therapy for lymphoma patients in remission.
As illustrated below, in the adjuvant lymphoma group, all 17 patients had entered CR, with 14 patients in continued complete remission, or CCR, without relapsing. The duration of response ranged from approximately nine months to over five years. ​ ​ In both treatment groups, the multiTAA-specific T cell therapy was well tolerated, with no drug-related serious adverse events.
We believe our multiTAA-specific T cell therapy can be manufactured at a fraction of the cost of a gene-modified T cell product, with substantially reduced complexity of manufacturing. · No need for lymphodepletion before infusion.
We believe our multiTAA-specific T cell therapy represent a safe alternative to CAR-T cells and can be manufactured at a fraction of the cost of a gene-modified T cell product, with substantially reduced complexity of manufacturing. · Low incidence rate of adverse events.
This appears to compare favorably with published CD19 CAR-T studies that have been associated with substantial tolerability concerns, including one Phase 1 trial in which 95% of patients had Grade 3 or higher adverse events during treatment. · Appears to drive endogenous immune responses.
This appears to compare favorably with published CD19 CAR-T studies that have been associated with substantial tolerability concerns, including a Phase 1 trial in which 95% of patients had Grade 3 or higher adverse events during treatment and current investigations by the FDA regarding the risk of CAR-T cell therapies to potentially induce secondary cancers. · Capable of addressing a broad repertoire of cancer cells.
We intend to significantly leverage the knowledge, experience and advice of our scientific founders and advisors, as well as the institutional expertise of BCM and our other major institutional partners, to advance our therapies through the clinic and into commercialization. 6 Table of Contents Background and History of Cancer Immunotherapies Despite advances in options for treatment, cancer continues to be one of the main causes of death in developed countries.
We intend to significantly leverage the knowledge, experience and advice of our scientific founders and advisors, as well as the institutional expertise of BCM and our other major institutional partners, to advance our therapies through the clinic and into commercialization.
In August 2022, the FDA cleared the Company’s IND application for MT-601 for the treatment of patients with relapsed/refractory non-Hodgkin lymphoma who have failed or are ineligible to receive anti-CD19 CAR T cell treatment.
MT - 601 is a multiTAA-specific T cell product that specifically targets six different tumor antigens upregulated in lymphoma cells (Survivin, PRAME, WT1, NY-ESO-1, SSX-2, MAGEA-4). In August 2022, the FDA cleared our IND application for MT-601 for the treatment of patients with relapsed/refractory non-Hodgkin lymphoma who have failed or are ineligible to receive anti-CD19 CAR T cell treatment.
Subsequently, mAbs that targeted CTLA-4 and PD-1 became known as immune checkpoint inhibitors, or ICIs. Immune checkpoints are a means by which cancer cells inhibit or turn down the body’s immune response to cancer. By interfering with these cloaking mechanisms, ICIs have shown an ability to activate T cells, shrink tumors, and improve patient survival.
James Allison reported that monoclonal antibodies, or mAbs, blocking CTLA-4 could treat tumors in animal models. Subsequently, mAbs that targeted CTLA-4 and PD-1 became known as immune checkpoint inhibitors, or ICIs. Immune checkpoints are a means by which cancer cells inhibit or turn down the body’s immune response to cancer.
This process is referred to as antigen-negative tumor escape. 8 Table of Contents Our solution to the problem of tumor heterogeneity is the development of T cell products that simultaneously attack multiple tumor-expressed antigens and thereby enable more complete initial tumor targeting, thus minimizing the subsequent opportunity for the cancer to engage escape mechanisms.
Our solution to the problem of tumor heterogeneity is the development of T cell products that are intended to simultaneously attack multiple tumor-expressed antigens and thereby enable more complete initial tumor targeting, thus minimizing the subsequent opportunity for the cancer to engage escape mechanisms. ​ ​ We believe our proprietary multiTAA-specific T cell platform may have meaningful advantages over current CAR and TCR-engineered cell therapy approaches.
In this trial, we treated patients in remission and with active disease post-transplant.
In this trial, patients in remission with high risk for relapse, as well as patients with active disease post-transplant were treated.
Acute Myeloid Leukemia We are pursuing the development of MT-401 for the treatment of post-transplant AML as the lead indication for the multiTAA-specific T cell program. Currently, available treatments for post-transplant AML patients are limited and include donor lymphocyte infusion, which has an approximately 15% overall response rate but a 30% to 50% risk of severe and debilitating graft-versus-host disease.
In each trial, correlative studies showed significant expansion of multiTAA-specific T cells, as well as evidence of epitope spreading against tumor-associated antigens that were not targeted by the multiTAA-specific T cell therapy. 8 Table of Contents Acute Myeloid Leukemia To date, available treatments for post-transplant AML patients are limited and include donor lymphocyte infusion, which has an approximately 15% overall response rate but a 30% to 50% risk of severe and debilitating graft-versus-host disease.
As of January 2022, the multiTAA-specific T cell therapy was generally well tolerated by all of the patients enrolled in clinical trials in hematological and solid tumor indications with no incidences of cytokine release syndrome or neurotoxicity.
As of January 2024, the multiTAA-specific T cell therapy was generally well tolerated by the patients across clinical trials in hematological and solid tumor indications, and no treatment-related adverse events, including CRS or neurotoxicity, were attributed to the use of multiTAA-specific T cell therapies to date.
In patient results to date in this trial, observed therapeutic responses appear to be highly durable, with some patients being relapse-free beyond five years. · Non-gene modified. Unlike CAR and TCR-based approaches, the multiTAA-specific T cell therapy does not require genetic modification of T cells, a costly and complex process that significantly complicates the manufacturing of a patient product.
Unlike CAR and TCR-based approaches, the multiTAA-specific T cell therapy does not require genetic modification of T cells, a costly and complex process that significantly complicates the manufacturing of a patient product.
The cells are then cultured to proliferate, and the proliferated cells are infused into the patient. Upon infusion, the cells can target and eliminate cancerous cells. Unlike chemotherapy, which is unable to distinguish between healthy and malignant cells, T cells produced for immunotherapy can selectively attack cancer cells that express the target antigen(s).
Unlike chemotherapy, which is unable to distinguish between healthy and malignant cells, T cells produced for immunotherapy can selectively attack cancer cells that express the target antigen(s). This leads to a more effective treatment platform with fewer side effects.
A total of 32 patients received two protocol-specified infusions of multiTAA-specific T cells, 14 with Hodgkin lymphoma, or HL, and 18 with aggressive non-Hodgkin lymphoma, or NHL, [diffuse large B-cell lymphoma, or DLBCL, (n=12), mantle cell lymphoma, or MCL, (n=2), T-cell lymphoma (n=3) and composite lymphoma (HL and DLBCL, n=1)]. 15 Table of Contents As reported in a recent publication by Vasileiou et al., BCM had treated 15 patients with active disease, which we refer to as the active lymphoma group, all of whom had completed a follow-up period beyond three months post-infusion.
A total of 32 patients received two protocol-specified infusions of multiTAA-specific T cells, 14 with Hodgkin lymphoma, or HL, and 18 with aggressive non-Hodgkin lymphoma, or NHL, [diffuse large B-cell lymphoma, or DLBCL, (n=12), mantle cell lymphoma, or MCL, (n=2), T-cell lymphoma (n=3) and composite lymphoma (HL and DLBCL, n=1)].
Historically, cancer therapy has been constrained to surgery, radiation, and chemotherapy. More recently, advances in the understanding of the immune system’s role in cancer surveillance have led to immunotherapy becoming an important treatment approach. Cancer immunotherapy began with treatments that nonspecifically activated the immune system and had limited efficacy and/or significant toxicity.
Background and History of Cancer Immunotherapies Despite advances in options for treatment, cancer continues to be one of the main causes of death in developed countries. Historically, cancer therapy has been constrained to surgery, radiation, and chemotherapy. More recently, advances in the understanding of the immune system’s role in cancer surveillance have led to immunotherapy becoming an important treatment approach.
Recent clinical data from checkpoint inhibitors such as ipilimumab, nivolumab and pembrolizumab have confirmed both the validity of this approach and the importance of T cells as promising tools for the treatment of cancer. Despite these many advances, there persists a significant unmet need in cancer therapeutics.
By interfering with these cloaking mechanisms, ICIs have shown an ability to activate T cells, shrink tumors, and improve patient survival. Recent clinical data from checkpoint inhibitors such as ipilimumab, nivolumab and pembrolizumab have confirmed both the validity of this approach and the importance of T cells as promising tools for the treatment of cancer.
T cell immunotherapy involves the infusion of T cells into a patient. Immune cells used for immunotherapy treatments can either be collected from the patient (autologous) or harvested from a donor (allogeneic). The cells are retrieved and either genetically modified to express tumor-specific CARs or TCRs or stimulated with specific antigens.
T cell therapy, we believe has evolved as one of the most promising branches of immunotherapy. T cell immunotherapy involves the infusion of T cells into a patient. Immune cells used for immunotherapy treatments can either be collected from the patient (autologous) or harvested from a donor (allogeneic).
T Cell Therapy Overview The field of adoptive cell transfer is currently comprised primarily of CAR and TCR engineered T cells and has emerged from principles of basic immunology to become a paradigm-shifting clinical immunotherapy. T cell therapy has evolved as one of the most promising branches of immunotherapy.
These cellular therapies may avoid the long-term side effects associated with current treatments and have the potential to be effective regardless of the type of previous treatments patients have experienced. 5 Table of Contents T Cell Therapy Overview The field of adoptive cell transfer is currently comprised primarily of CAR and TCR engineered T cells and has emerged from principles of basic immunology to become a paradigm-shifting clinical immunotherapy.
We are pursuing post-transplant AML as the lead indication for the multiTAA-specific T cell program using our allogeneic therapies. ● Off-the-shelf multiTAA-specific T cell therapies - We plan to enroll patients that will be matched to the pre-manufactured inventory of MT-401-OTS products based on their human leukocyte antigen, or HLA.
We plan to enroll patients that will be matched to the pre-manufactured inventory of MT - 401 - OTS products based on their human leukocyte antigen, or HLA. Because the MT-401-OTS product inventory is pre-manufactured, the T cell product is delivered to the patient in a significantly shorter amount of time than a patient-specific T cell product.
For example, in BCM’s Phase 1 clinical trial in lymphoma, there were complete responses, or CRs, in six of the fifteen evaluable patients with active disease. Significantly, no patient with a CR has subsequently relapsed with disease, whereas typically 30% or more of patients with CR in reported CAR-T studies relapse within one year.
For example, in BCM’s Phase 1 clinical trial in lymphoma, there were complete responses, or CRs, in six of the fifteen evaluable patients with both Hodgkin lymphoma and non-Hodgkin lymphoma with active disease.

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Item 1A. Risk Factors

Risk Factors — what could go wrong, per management

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Biggest changeWe may be subject to claims that our employees, consultants or independent contractors have wrongfully used or disclosed confidential information of third parties. As is common in the biotechnology and pharmaceutical industries, in addition to our employees, we engage the services of consultants to assist us in the development of our product candidates.
Biggest changeAs is common in the biotechnology and pharmaceutical industries, in addition to our employees, we engage the services of consultants to assist us in the development of our product candidates. We have received confidential and proprietary information from third parties. We employ individuals or engage consultants who were previously employed at other biotechnology or pharmaceutical companies.
The success of our multiTAA product candidates or any other product candidates that we develop or otherwise may acquire will depend on several factors, including: ● timely and successful completion of preclinical studies, including toxicology studies, biodistribution studies and minimally efficacious dose studies in animals, where applicable, and clinical trials; ● effective investigational new drug applications, or INDs, from the FDA or comparable foreign applications that allow commencement of our planned clinical trials or future clinical trials for our product candidates; ● sufficiency of our financial and other resources to complete the necessary preclinical studies and clinical trials; ● successful enrollment and completion of clinical trials, including under the FDA’s current Good Clinical Practices, or GCPs, and current Good Laboratory Practices; ● successful development of, or making arrangements with third-party manufacturers for, our commercial manufacturing processes for any of our product candidates that receive regulatory approval; ● receipt of timely marketing approvals from applicable regulatory authorities; ● launching commercial sales of products, if approved, whether alone or in collaboration with others; ● acceptance of the benefits and use of our products, including method of administration, if approved, by patients, the medical community and third-party payors, for their approved indications; ● the prevalence and severity of adverse events experienced by our product candidates; ● the availability, perceived advantages, cost, safety and efficacy of alternative therapies for any product candidate, and any indications for such product candidate, that we develop; ● our ability to produce any product candidates we develop on a commercial scale; ● obtaining and maintaining patent, trademark and trade secret protection and regulatory exclusivity for our product candidates and otherwise protecting our rights in our intellectual property portfolio; ● maintaining compliance with regulatory requirements, including the FDA’s current Good Manufacturing Practices, or cGMPs, and complying effectively with other procedures; ● obtaining and maintaining third-party coverage and adequate reimbursement and patients’ willingness to pay out-of-pocket in the absence of such coverage and adequate reimbursement; and 37 Table of Contents ● maintaining a continued acceptable safety, tolerability and efficacy profile of the products following approval.
The success of our multiTAA product candidates or any other product candidates that we develop or otherwise may acquire will depend on several factors, including: ● timely and successful completion of preclinical studies, including toxicology studies, biodistribution studies and minimally efficacious dose studies in animals, where applicable, and clinical trials; ● effective investigational new drug applications, or INDs, from the FDA or comparable foreign applications that allow commencement of our planned clinical trials or future clinical trials for our product candidates; ● sufficiency of our financial and other resources to complete the necessary preclinical studies and clinical trials; 30 Table of Contents ● successful enrollment and completion of clinical trials, including under the FDA’s current Good Clinical Practices, or GCPs, and current Good Laboratory Practices; ● successful development of, or making arrangements with third-party manufacturers for, our commercial manufacturing processes for any of our product candidates that receive regulatory approval; ● receipt of timely marketing approvals from applicable regulatory authorities; ● launching commercial sales of products, if approved, whether alone or in collaboration with others; ● acceptance of the benefits and use of our products, including method of administration, if approved, by patients, the medical community and third-party payors, for their approved indications; ● the prevalence and severity of adverse events experienced by our product candidates; ● the availability, perceived advantages, cost, safety and efficacy of alternative therapies for any product candidate, and any indications for such product candidate, that we develop; ● our ability to produce any product candidates we develop on a commercial scale; ● obtaining and maintaining patent, trademark and trade secret protection and regulatory exclusivity for our product candidates and otherwise protecting our rights in our intellectual property portfolio; ● maintaining compliance with regulatory requirements, including the FDA’s current Good Manufacturing Practices, or cGMPs, and complying effectively with other procedures; ● obtaining and maintaining third-party coverage and adequate reimbursement and patients’ willingness to pay out-of-pocket in the absence of such coverage and adequate reimbursement; and ● maintaining a continued acceptable safety, tolerability and efficacy profile of the products following approval.
These risks and uncertainties include the following: ● the USPTO and various foreign governmental patent agencies require compliance with a number of procedural, documentary, fee payment and other provisions during the patent process, the noncompliance with which can result in abandonment or lapse of a patent or patent application, and partial or complete loss of patent rights in the relevant jurisdiction; ● patent applications may not result in any patents being issued; ● patents that may be issued or in-licensed may be challenged, invalidated, modified, revoked, circumvented, found to be unenforceable or otherwise may not provide any competitive advantage; ● our competitors, many of whom have substantially greater resources than us, and many of whom have made significant investments in competing technologies, may seek or may have already obtained patents that will limit, interfere with or eliminate our ability to make, use and sell our potential product candidates; ● there may be significant pressure on the U.S. government and international governmental bodies to limit the scope of patent protection both inside and outside the United States for disease treatments that prove successful, as a matter of public policy regarding worldwide health concerns; and ● countries other than the United States may have patent laws less favorable to patentees than those upheld by U.S. courts, allowing foreign competitors a better opportunity to create, develop and market competing product candidates.
These risks and uncertainties include the following: ● the USPTO and various foreign governmental patent agencies require compliance with a number of procedural, documentary, fee payment and other provisions during the patent process, the noncompliance with which can result in abandonment or lapse of a patent or patent application, and partial or complete loss of patent rights in the relevant jurisdiction; ● patent applications may not result in any patents being issued; ● patents that may be issued or in-licensed may be challenged, invalidated, modified, revoked, circumvented, found to be unenforceable or otherwise may not provide any competitive advantage; 48 Table of Contents ● our competitors, many of whom have substantially greater resources than us, and many of whom have made significant investments in competing technologies, may seek or may have already obtained patents that will limit, interfere with or eliminate our ability to make, use and sell our potential product candidates; ● there may be significant pressure on the U.S. government and international governmental bodies to limit the scope of patent protection both inside and outside the United States for disease treatments that prove successful, as a matter of public policy regarding worldwide health concerns; and ● countries other than the United States may have patent laws less favorable to patentees than those upheld by U.S. courts, allowing foreign competitors a better opportunity to create, develop and market competing product candidates.
Remote work policies, quarantines, shelter-in-place and similar government orders, shutdowns or other restrictions on the conduct of business operations related to the COVID-19 pandemic or other health epidemics may negatively impact productivity. For instance, the COVID-19 pandemic disrupted our ongoing research and development activities and delayed certain of our clinical programs and timelines.
Remote work policies, quarantines, shelter-in-place and similar government orders, shutdowns or other restrictions on the conduct of business operations related to the pandemics or other health epidemics may negatively impact productivity. For instance, the COVID-19 pandemic disrupted our ongoing research and development activities and delayed certain of our clinical programs and timelines.
Although we have an exclusive license agreement with BCM under which we received a worldwide, exclusive license to BCM’s rights in and to three patent families to develop and commercialize the multiTAA-specific T cell product candidates, we will need to enter into additional agreements with BCM with respect to (i) a strategic alliance to advance preclinical research, early stage clinical trials, and Phase 2 clinical trials with respect to our product candidates, as well as continued access to our clinical data, and (ii) support, including personnel and space at the institution for the foreseeable future.
Although we have an exclusive license agreement with BCM under which we received a worldwide, exclusive license to BCM’s rights in and to three patent families to develop and commercialize the multiTAA-specific T cell product candidates, we will need to enter into additional agreements with BCM with respect to (i) a strategic alliance to advance preclinical research, early stage clinical trials, and clinical trials with respect to our product candidates, as well as continued access to our clinical data, and (ii) support, including personnel and space at the institution for the foreseeable future.
Market acceptance of our product candidates, if we receive approval, depends on a number of factors, including the: ● efficacy and safety of our product candidates as demonstrated in clinical trials and post-marketing experience; ● clinical indications for which our product candidates may be approved; ● acceptance by physicians and patients of our product candidates as safe and effective; ● potential and perceived advantages of our product candidates over alternative treatments; ● safety of our product candidates seen in a broader patient group, including our use outside the approved indications should physicians choose to prescribe for such uses; ● prevalence and severity of any side effects; ● product labeling, or product insert requirements of the FDA or other regulatory authorities; ● timing of market introduction of our product candidates as well as competitive products; ● cost in relation to alternative treatments; ● pricing and the availability of coverage and adequate reimbursement by third-party payors and government authorities; ● relative convenience and ease of administration; and ● effectiveness of any sales and marketing efforts.
Market acceptance of our product candidates, if we receive approval, depends on a number of factors, including the: ● efficacy and safety of our product candidates as demonstrated in clinical trials and post-marketing experience; ● clinical indications for which our product candidates may be approved; ● acceptance by physicians and patients of our product candidates as safe and effective; ● potential and perceived advantages of our product candidates over alternative treatments; ● safety of our product candidates seen in a broader patient group, including our use outside the approved indications should physicians choose to prescribe for such uses; 42 Table of Contents ● prevalence and severity of any side effects; ● product labeling, or product insert requirements of the FDA or other regulatory authorities; ● timing of market introduction of our product candidates as well as competitive products; ● cost in relation to alternative treatments; ● pricing and the availability of coverage and adequate reimbursement by third-party payors and government authorities; ● relative convenience and ease of administration; and ● effectiveness of any sales and marketing efforts.
Any of these events could have a material adverse effect on our reputation, business, or financial condition, including but not limited to: interruptions or stoppages in our business operations (including clinical trials); inability to process personal data or to operate in certain jurisdictions; limited ability to develop or commercialize our products; expenditure of time and resources to defend any claim or inquiry; adverse publicity; or substantial changes to our business model or operations. ​ 66 Table of Contents Risks Related to our Securities The price of our stock may be volatile.
Any of these events could have a material adverse effect on our reputation, business, or financial condition, including but not limited to: interruptions or stoppages in our business operations (including clinical trials); inability to process personal data or to operate in certain jurisdictions; limited ability to develop or commercialize our products; expenditure of time and resources to defend any claim or inquiry; adverse publicity; or substantial changes to our business model or operations. ​ 61 Table of Contents Risks Related to our Securities The price of our stock may be volatile.
Such laws include: ● the federal Anti-Kickback Statute which prohibits, among other things, persons and entities from knowingly and willfully soliciting, offering, receiving or providing remuneration, directly or indirectly, in cash or in kind, to induce or reward, or in return for, either the referral of an individual for, or the purchase, order or recommendation of, any good or service, for which payment may be made under a federal healthcare program such as Medicare and Medicaid; ● the federal civil and criminal false claims laws, including the federal civil False Claims Act, and civil monetary penalties laws, which impose criminal and civil penalties against individuals or entities for, among other things, knowingly presenting, or causing to be presented, to the federal government, claims for payment that are false or fraudulent or making a false statement to avoid, decrease or conceal an obligation to pay money to the federal government; ● the federal Health Insurance Portability and Accountability Act of 1996, or HIPAA, which imposes criminal and civil liability for, among other things, executing a scheme to defraud any healthcare benefit program or making false statements relating to healthcare matters; ● HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act, or HITECH, and its implementing regulations, which also imposes obligations, including mandatory contractual terms, on covered entities, including certain healthcare providers, health plans, and healthcare clearinghouses, and their respective business associates that create, receive, maintain or transmit individually identifiable health information for or on behalf of a covered entity as well as their covered subcontractors, with respect to safeguarding the privacy, security and transmission of individually identifiable health information; ● the federal Physician Payments Sunshine Act, which requires certain manufacturers of drugs, devices, biologics and medical supplies for which payment is available under Medicare, Medicaid or the Children’s Health Insurance Program, with specific exceptions, to report annually to CMS, information related to payments or other transfers of value made to physicians (defined to include doctors, dentists, optometrists, podiatrists and chiropractors), other health care professionals)(such as physician assistants and nurse practitioners) and teaching hospitals, as well as information regarding ownership and investment interests held by physicians and their immediate family members; and ● analogous state, local, and foreign laws and regulations, such as state anti-kickback and false claims laws, which may apply to sales or marketing arrangements and claims involving healthcare items or services reimbursed by non-governmental third party payors, including private insurers; state laws that require pharmaceutical companies to comply with the pharmaceutical industry’s voluntary compliance guidelines and the relevant compliance guidance promulgated by the federal government; state 63 Table of Contents laws that require drug manufacturers to report information related to payments and other transfers of value to physicians and other healthcare providers or marketing expenditures or drug pricing; state and local laws that require the registration of pharmaceutical sales representatives; state and local “drug takeback” laws and regulations; and state and foreign laws governing the privacy and security of health information in some circumstances, many of which differ from each other in significant ways and often are not preempted by HIPAA, thus complicating compliance efforts.
Such laws include: ● the federal Anti-Kickback Statute which prohibits, among other things, persons and entities from knowingly and willfully soliciting, offering, receiving or providing remuneration, directly or indirectly, in cash or in kind, to induce or reward, or in return for, either the referral of an individual for, or the purchase, order or recommendation of, any good or service, for which payment may be made under a federal healthcare program such as Medicare and Medicaid; ● the federal civil and criminal false claims laws, including the federal civil False Claims Act, and civil monetary penalties laws, which impose criminal and civil penalties against individuals or entities for, among other things, knowingly presenting, or causing to be presented, to the federal government, claims for payment that are false or fraudulent or making a false statement to avoid, decrease or conceal an obligation to pay money to the federal government; ● the federal Health Insurance Portability and Accountability Act of 1996, or HIPAA, which imposes criminal and civil liability for, among other things, executing a scheme to defraud any healthcare benefit program or making false statements relating to healthcare matters; ● HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act, or HITECH, and its implementing regulations, which also imposes obligations, including mandatory contractual terms, on covered entities, including certain healthcare providers, health plans, and healthcare clearinghouses, and their respective business associates that create, receive, maintain or transmit individually identifiable health information for or on behalf of a covered entity as well as their covered subcontractors, with respect to safeguarding the privacy, security and transmission of individually identifiable health information; ● the federal Physician Payments Sunshine Act, which requires certain manufacturers of drugs, devices, biologics and medical supplies for which payment is available under Medicare, Medicaid or the Children’s Health Insurance Program, with specific exceptions, to report annually to CMS, information related to payments or other transfers of value made to physicians (defined to include doctors, dentists, optometrists, podiatrists and chiropractors), other health care professionals)(such as physician assistants and nurse practitioners) and teaching hospitals, as well as information regarding ownership and investment interests held by physicians and their immediate family members; and ● analogous state, local, and foreign laws and regulations, such as state anti-kickback and false claims laws, which may apply to sales or marketing arrangements and claims involving healthcare items or services reimbursed by non-governmental third - party payors, including private insurers; state laws that require pharmaceutical companies to comply with the pharmaceutical industry’s voluntary compliance guidelines and the relevant compliance guidance promulgated by the federal government; state laws that require drug manufacturers to report information related to payments and other transfers of value to physicians and other healthcare providers or marketing expenditures or drug pricing; state and local laws that require the registration of pharmaceutical sales representatives; state and local “drug takeback” laws and regulations; and state and foreign laws governing the privacy and security of health information in some circumstances, many of which differ from each other in significant ways and often are not preempted by HIPAA, thus complicating compliance efforts. 58 Table of Contents Efforts to ensure that our business arrangements will comply with applicable healthcare laws may involve substantial costs.
While it is not possible to predict whether and when any such changes will occur, changes in the laws, regulations, and policies governing the development and approval of our product candidates and the commercialization, importation, and reimbursement of our product candidates could adversely affect our business. 65 Table of Contents We are subject to stringent and changing laws, regulations, rules, contractual obligations, policies and other obligations related to data privacy and security.
While it is not possible to predict whether and when any such changes will occur, changes in the laws, regulations, and policies governing the development and approval of our product candidates and the commercialization, importation, and reimbursement of our product candidates could adversely affect our business. 60 Table of Contents We are subject to stringent and changing laws, regulations, rules, contractual obligations, policies and other obligations related to data privacy and security.
Disputes may arise regarding our rights to intellectual property licensed to us from a third party, including but not limited to: 57 Table of Contents ● the scope of rights granted under the license agreement and other interpretation-related issues; ● the extent to which our technology and processes infringe on intellectual property of the licensor that is not subject to the licensing agreement; ● the sublicensing of patent and other rights; ● our diligence obligations under the license agreement and what activities satisfy those diligence obligations; ● the ownership of inventions and know-how resulting from the creation or use of intellectual property by us, alone or with our licensors and collaborators; ● the scope and duration of our payment obligations; ● our rights upon termination of such agreement; and ● the scope and duration of exclusivity obligations of each party to the agreement.
Disputes may arise regarding our rights to intellectual property licensed to us from a third - party, including but not limited to: ● the scope of rights granted under the license agreement and other interpretation-related issues; ● the extent to which our technology and processes infringe on intellectual property of the licensor that is not subject to the licensing agreement; ● the sublicensing of patent and other rights; ● our diligence obligations under the license agreement and what activities satisfy those diligence obligations; ● the ownership of inventions and know-how resulting from the creation or use of intellectual property by us, alone or with our licensors and collaborators; ● the scope and duration of our payment obligations; ● our rights upon termination of such agreement; and ● the scope and duration of exclusivity obligations of each party to the agreement.
Vera is a co-founder and director of Allovir Inc., or Allovir. Allovir has technology which is being developed under a license agreement with BCM by the same research group at BCM. Allovir is a clinical-stage biopharmaceutical company that is investigating and developing virus-specific T cell therapy technology for the prevention and/or treatment of viral infections. Accordingly, Dr.
Dr. Vera is a co-founder and director of Allovir Inc., or Allovir. Allovir has technology which is being developed under a license agreement with BCM by the same research group at BCM. Allovir is a clinical-stage biopharmaceutical company that is investigating and developing virus-specific T cell therapy technology for the prevention and/or treatment of viral infections. Further, Dr.
Moreover, any of these events could prevent us from achieving or maintaining market acceptance of the particular product candidate, if approved, and could significantly harm our business, results of operations and prospects. 42 Table of Contents We may not obtain or maintain the benefits associated with orphan drug designation, including market exclusivity.
Moreover, any of these events could prevent us from achieving or maintaining market acceptance of the particular product candidate, if approved, and could significantly harm our business, results of operations and prospects. 35 Table of Contents We may not obtain or maintain the benefits associated with orphan drug designation, including market exclusivity.
Some of our suppliers may not have the capacity to support commercial products manufactured under cGMP by biopharmaceutical firms or may otherwise be ill-equipped to support our needs. We also may not have supply contracts with many of these suppliers and may not be able to obtain supply contracts with them on acceptable terms or at all.
Some of our direct or indirect suppliers may not have the capacity to support commercial products manufactured under cGMP by biopharmaceutical firms or may otherwise be ill-equipped to support our needs. We also may not have supply contracts with many of these suppliers and may not be able to obtain supply contracts with them on acceptable terms or at all.
The loss of the services of any of our executive officers, other key employees, and other scientific and medical advisors, and our inability to find suitable replacements could result in delays in product development and harm to our business. We have a priority to quickly train additional qualified scientific and medical personnel to ensure the ability to maintain business continuity.
The loss of the services of any of our executive officer, other key employees, and other scientific and medical advisors, and our inability to find suitable replacements could result in delays in product development and harm to our business. We have a priority to quickly train additional qualified scientific and medical personnel to ensure the ability to maintain business continuity.
Regardless of the merits or eventual outcome, liability claims may result in: ● decreased demand for our product candidates; ● injury to our reputation; ● withdrawal of clinical trial participants; ● initiation of investigations by regulators; ● costs to defend the related litigation; ● a diversion of management’s time and our resources; ● substantial monetary awards to trial participants or patients; ● product recalls, withdrawals or labeling, marketing or promotional restrictions; ● loss of revenue; ● exhaustion of any available insurance and our capital resources; and 52 Table of Contents ● the inability to commercialize any product candidate.
Regardless of the merits or eventual outcome, liability claims may result in: ● decreased demand for our product candidates; ● injury to our reputation; ● withdrawal of clinical trial participants; ● initiation of investigations by regulators; ● costs to defend the related litigation; ● a diversion of management’s time and our resources; ● substantial monetary awards to trial participants or patients; ● product recalls, withdrawals or labeling, marketing or promotional restrictions; ● loss of revenue; ● exhaustion of any available insurance and our capital resources; and ● the inability to commercialize any product candidate.
Preclinical studies and clinical trials often fail to demonstrate safety or efficacy of the product candidate studied for the target indication. 41 Table of Contents In addition to side effects caused by the product candidate, the administration process or related procedures also can cause adverse side effects.
Preclinical studies and clinical trials often fail to demonstrate safety or efficacy of the product candidate studied for the target indication. 34 Table of Contents In addition to side effects caused by the product candidate, the administration process or related procedures also can cause adverse side effects.
While we obtained clinical trial insurance for our Phase 2 clinical trials, we may have to pay amounts awarded by a court or negotiated in a settlement that exceed our coverage limitations or that are not covered by our insurance, and we may not have, or be able to obtain, sufficient capital to pay such amounts.
While we obtained clinical trial insurance for our clinical trials, we may have to pay amounts awarded by a court or negotiated in a settlement that exceed our coverage limitations or that are not covered by our insurance, and we may not have, or be able to obtain, sufficient capital to pay such amounts.
Any of the previously identified or similar threats could cause a security incident or other incident during which our information technology systems or data could be compromised, which could result in unauthorized, unlawful, or accidental acquisition, modification, destruction, loss, alteration, encryption, disclosure of, or access to our data; it could also disrupt our ability (and that of third parties upon which we rely) to operate our business, including conducting our clinical trials.
Any of the previously identified or similar threats could cause a security incident or other incident during which our information technology systems or data could be compromised, which could result in unauthorized, unlawful, or accidental acquisition, modification, destruction, loss, alteration, encryption, disclosure 64 Table of Contents of, or access to our data; it could also disrupt our ability (and that of third parties upon which we rely) to operate our business, including conducting our clinical trials.
If we are unable to conclude that our internal control over financial reporting is effective, or if our independent registered public accounting firm determines we have a material weakness or significant deficiency in our internal control over financial reporting, we could lose investor confidence in the accuracy and completeness of our financial reports, the market price of our common stock could decline, and we could be subject to sanctions or investigations by the Nasdaq, the SEC or other regulatory authorities.
If we are unable to conclude that our internal control over financial reporting is effective, or if our independent registered public accounting firm determines we have a material weakness or significant deficiency in our internal control over financial reporting, we could lose investor confidence in the accuracy and completeness of our financial reports, the market price of our common 65 Table of Contents stock could decline, and we could be subject to sanctions or investigations by the Nasdaq, the SEC or other regulatory authorities.
Risks Related to our Financial Position and Capital Needs We are a development stage company with a history of operating losses, and we expect losses to continue for the indefinite future. These factors raise substantial doubt regarding our ability to continue as a going concern.
Risks Related to our Financial Position and Capital Needs We are a clinical stage company with a history of operating losses, and we expect losses to continue for the indefinite future. These factors raise substantial doubt regarding our ability to continue as a going concern.
Those factors that could cause fluctuations include, but are not limited to, the following: ● price and volume of fluctuations in the overall stock market from time to time; ● fluctuations in stock market prices and trading volumes of similar companies; ● the thinly traded nature of our common stock; ● actual or anticipated changes in our net loss or fluctuations in our operating results or in the expectations of securities analysts; ● results of our preclinical studies and clinical trials or delays in anticipated timing; ● the issuance of new equity securities pursuant to a future offering, including issuances of preferred stock , or sales of large blocks of our stock and sales by insiders and our institutional investors; ● announcements of new collaboration agreements with strategic partners or developments by our existing collaboration partners; ● announcements of acquisitions, mergers or business combinations; ● competitive developments, including announcements by competitors of new products or services or significant contracts, acquisitions, strategic partnerships, joint ventures or capital commitments; ● general economic conditions and trends, including changes in interest rates, and other national and global conditions, including the ongoing COVID-19 pandemic and related global economic uncertainty; ● major catastrophic events; ● departures of key personnel; ● events affecting BCM or any future collaborators; ● announcements of new product candidates or technologies, commercial relationships or other events , including the results of clinical trials, or variations in our quarterly operating results; ● regulatory developments in the United States and other countries , including changes in the structure of healthcare payment systems, or other positive and negative events relating to healthcare and the overall pharmaceutical and biotechnology sectors; ● failure of our common stock to maintain listing requirements on Nasdaq; ● the outcome of any litigation to which we are a party; ● changes in accounting principles; and 67 Table of Contents ● discussion of our company or our stock price by the financial and scientific press and in online investor communities.
Those factors that could cause fluctuations include, but are not limited to, the following: ● price and volume of fluctuations in the overall stock market from time to time; ● fluctuations in stock market prices and trading volumes of similar companies; ● the thinly traded nature of our common stock; ● actual or anticipated changes in our net loss or fluctuations in our operating results or in the expectations of securities analysts; ● results of our preclinical studies and clinical trials or delays in anticipated timing; ● the issuance of new equity securities pursuant to a future offering, including issuances of preferred stock , or sales of large blocks of our stock and sales by insiders and our institutional investors; ● announcements of new collaboration agreements with strategic partners or developments by our existing collaboration partners; ● announcements of acquisitions, mergers or business combinations; ● competitive developments, including announcements by competitors of new products or services or significant contracts, acquisitions, strategic partnerships, joint ventures or capital commitments; ● general economic conditions and trends, including changes in interest rates, and other national and global conditions, including pandemics and related global economic uncertainty; ● major catastrophic events; ● departures of key personnel; ● events affecting BCM, Cell Ready or any future collaborators; ● announcements of new product candidates or technologies, commercial relationships or other events , including the results of clinical trials, or variations in our quarterly operating results; ● regulatory developments in the United States and other countries , including changes in the structure of healthcare payment systems, or other positive and negative events relating to healthcare and the overall pharmaceutical and biotechnology sectors; ● failure of our common stock to maintain listing requirements on Nasdaq; ● the outcome of any litigation to which we are a party; ● changes in accounting principles; and 62 Table of Contents ● discussion of our company or our stock price by the financial and scientific press and in online investor communities.
For example, in the fourth quarter of 2019 the FDA placed a clinical hold on our IND of MT-401 for the treatment of patients with post-transplant AML and requested certain 39 Table of Contents information regarding quality and technical specifications for two reagents supplied by third party vendors that are used in our manufacturing process but not present in the final product infused to patients.
For example, in the fourth quarter of 2019 the FDA placed a clinical hold on our IND of MT-401 for the treatment of patients with post-transplant AML and requested certain information regarding quality and technical specifications for two reagents supplied by third-party vendors that are used in our manufacturing process but not present in the final product infused to patients.
It is also unclear how such challenges and the healthcare reform measures of the Biden administration will impact the ACA and our business. 64 Table of Contents In addition, other federal health reform measures have been proposed and adopted in the United States.
It is also unclear how such challenges and the healthcare reform measures of the Biden administration will impact the ACA and our business. 59 Table of Contents In addition, other federal health reform measures have been proposed and adopted in the United States.
In the event of a major hurricane or other serious weather event or catastrophic event such as fire, power loss, cyberattack, war, terrorist attack or epidemic or pandemic, such as the COVID-19 pandemic, that impacts our corporate headquarters or other facilities, or the facilities of any third parties on which we may rely, we may be unable to continue our operations and may experience delays in our manufacturing process and shipment of clinical supply to trial sites or interruptions in our clinical trials and research activities, all of which could delay our development plans and materially harm our business, results of operations and prospects.
In the event of a major hurricane or other serious weather event or catastrophic event such as fire, power loss, cyberattack, war, terrorist attack or epidemic or pandemic that impacts the facilities of any third parties on which we may rely, we may be unable to continue our operations and may experience delays in our manufacturing process and shipment of clinical supply to trial sites or interruptions in our clinical trials and research activities, all of which could delay our development plans and materially harm our business, results of operations and prospects.
These risks are described more fully in this “Risk Factors” section and include, among others: ● We are a development stage company with a history of operating losses, and we expect losses to continue for the indefinite future.
These risks are described more fully in this “Risk Factors” section and include, among others: ● We are a clinical stage company with a history of operating losses, and we expect losses to continue for the indefinite future.
In addition, certain of our immunotherapies may be subject to competition from investigational new drugs and/or products developed using other technologies, some of which have completed numerous clinical trials. The market opportunities for our product candidates may be limited to those patients who are ineligible for or have failed prior treatments and may be small.
In addition, certain of our immunotherapies may be subject to competition from investigational new drugs and/or products developed using other technologies, some of which have completed numerous clinical trials. 45 Table of Contents The market opportunities for our product candidates may be limited to those patients who are ineligible for or have failed prior treatments and may be small.
We will be able to protect our proprietary rights from unauthorized use by third parties only to the extent that our technologies, methods of treatment, 59 Table of Contents product candidates, and any future products are covered by valid and enforceable patents or are effectively maintained as trade secrets and we have the funds to enforce our rights, if necessary.
We will be able to protect our proprietary rights from unauthorized use by third parties only to the extent that our technologies, methods of treatment, product candidates, and any future products are covered by valid and enforceable patents or are effectively maintained as trade secrets and we have the funds to enforce our rights, if necessary.
In addition, it is uncertain if and to what extent various states will conform to federal tax legislation. The impact of such changes or future legislation could increase our U.S. tax expense and could have a material adverse impact on our business and financial condition. ​ ITEM 1B. UNRESOLVED STAFF COMMENTS None.
In addition, it is uncertain if and to what extent various states will conform to federal tax legislation. The impact of such changes or future legislation could increase our U.S. tax expense and could have a material adverse impact on our business and financial condition. ​ ITEM 1B. UNRESOLVED STAFF COMMENTS None. ​ 67 Table of Contents
If we are unsuccessful in securing such strategic collaborations, we may be unable to commercialize any approved products as we have not yet licensed, marketed or sold any of our immunotherapies or entered into successful collaborations for these services in order to ultimately commercialize our immunotherapies. Establishing strategic collaborations is difficult and time-consuming.
If we are unsuccessful in securing such strategic collaborations, we may be unable to commercialize any approved products as we have not yet licensed, marketed or sold any of our immunotherapies or entered into successful collaborations for these services in order to ultimately commercialize our immunotherapies. Establishing strategic collaborations is difficult and time- 41 Table of Contents consuming.
We cannot predict the breadth of claims that may be allowed or enforced in our patents or in third-party patents. For example, on September 16, 2011, the Leahy-Smith America Invents Act, or Leahy-Smith Act, was signed into law. The Leahy-Smith Act includes a number of significant changes to U.S. patent law.
We cannot predict the breadth of claims that may be allowed or 50 Table of Contents enforced in our patents or in third-party patents. For example, on September 16, 2011, the Leahy-Smith America Invents Act, or Leahy-Smith Act, was signed into law. The Leahy-Smith Act includes a number of significant changes to U.S. patent law.
We depend on a limited number of vendors for supply of certain materials and equipment used in the manufacture of our multiTAA-specific T cell therapy-based product candidates. For example, we purchase equipment and reagents critical for the manufacture of our product candidates from Wilson Wolf (a company controlled by our director John Wilson), Almac and other suppliers.
We depend on a limited number of vendors for supply of certain materials and equipment used in the manufacture of our multiTAA-specific T cell therapy-based product candidates. For example, in the past, we purchased equipment and reagents critical for the manufacture of our product candidates from Wilson Wolf (a company controlled by our director John Wilson), Almac and other suppliers.
For products administered under the supervision of a physician, obtaining coverage and adequate reimbursement may be particularly difficult because of the higher prices often associated with such drugs. Additionally, separate reimbursement for the product itself or the treatment or procedure in which the product is used may not be available, which may impact physician utilization.
For products administered under the supervision of a physician, obtaining coverage and adequate reimbursement may be particularly difficult because of the higher prices 43 Table of Contents often associated with such drugs. Additionally, separate reimbursement for the product itself or the treatment or procedure in which the product is used may not be available, which may impact physician utilization.
Although we expect our in-house cGMP manufacturing facility to be our primary source of multiTAA-specific T cell therapy-based product candidates and for commercial manufacturing of any products, if approved, we intend to evaluate potential third- party manufacturing capabilities in order to provide potential multiple sources of clinical and commercial supply.
Although we expect Cell Ready’s cGMP manufacturing facility to be our primary source of multiTAA-specific T cell therapy-based product candidates and for commercial manufacturing of any products, if approved, we intend to evaluate additional potential third-party manufacturing capabilities in order to provide potential multiple sources of clinical and commercial supply.
In addition, upon a liquidity event (as defined in our BCM license agreement with BCM) of the licensee under the BCM license agreement (which, the licensee shall be the Company), BCM will receive a liquidity incentive payment of 0.5% of the liquidity event proceeds (as defined in the BCM license agreement) received by such licensee or its stockholders in the liquidity event, thereby diluting the amount of proceeds available to the licensee or its stockholders in a liquidity event.
In addition, upon a liquidity event (as defined in our BCM license agreement with BCM) of the licensee under the BCM license agreement (which, the licensee shall be the Company), BCM will receive a liquidity incentive payment of 0.5% of the liquidity event 52 Table of Contents proceeds (as defined in the BCM license agreement) received by such licensee or its stockholders in the liquidity event, thereby diluting the amount of proceeds available to the licensee or its stockholders in a liquidity event.
The lengthy approval process, as well as the unpredictability of future clinical trial results, may result in us failing to obtain regulatory approval for our product candidates, which would materially harm our business, results of operations and prospects. The results of earlier preclinical and clinical trials may not be predictive of future clinical trial results.
The lengthy approval process, as well as the unpredictability of future clinical trial results, may result in us failing to obtain regulatory approval for our product candidates, which would materially harm our business, results of operations and prospects. 33 Table of Contents The results of earlier preclinical and clinical trials may not be predictive of future clinical trial results.
A conflict of interest also may arise concerning the timing and scope of the parties’ planned and ongoing clinical trials, investigational new drug application filings and the parties’ opportunities for marketing their respective product candidates, as well as our intellectual property rights with those of Allovir.
A conflict of interest also may arise concerning the timing and scope of the parties’ planned and ongoing clinical trials, investigational new drug application filings and the parties’ opportunities for marketing their respective product candidates, as well as 47 Table of Contents our intellectual property rights with those of Allovir.
Our ability to pursue our planned business activities depends upon our successful efforts to raise additional financing, which may be adversely impacted by potential worsening global economic conditions, including decades-high inflation and concerns of a recession in the United States or other major markets, and the recent disruptions to and volatility in the credit and financial markets in the United States and worldwide, including from the COVID-19 pandemic.
Our ability to pursue our planned business activities depends upon our successful efforts to raise additional financing, which may be adversely impacted by potential worsening global economic conditions, including decades-high inflation and concerns of a recession in the United States or other major markets, and the recent disruptions to and volatility in the credit and financial markets in the United States and worldwide.
Any of these challenges could delay completion of clinical trials, require bridging clinical trials or the repetition of one or more clinical trials, increase clinical trial costs, delay approval of our 43 Table of Contents product candidate, impair commercialization efforts, increase our cost of goods, and have an adverse effect on our clinical development and/or commercialization plans.
Any of these challenges could delay completion of clinical trials, require bridging clinical trials or the repetition of one or more clinical trials, increase clinical trial costs, delay approval of our product candidate, impair commercialization efforts, increase our cost of goods, and have an adverse effect on our clinical development and/or commercialization plans.
Clinical trials are expensive and difficult to design and implement, in part because they are subject to rigorous regulatory requirements. Because our product candidates are based on new technologies and manufactured on a patient-by-patient basis for our multiTAA-specific T cell product candidates we expect that they will require extensive research and development and have substantial manufacturing costs.
Clinical trials are expensive and difficult to design and implement, in part because they are subject to rigorous regulatory requirements. Because our product candidates are based on new technologies and manufactured on a patient-by-patient basis for our multiTAA-specific T cell product candidates we expect that they will have substantial manufacturing costs.
Even if favorable coverage and reimbursement status is attained for one or more products for which we receive regulatory approval, less favorable coverage policies and reimbursement rates may be implemented in the future. 49 Table of Contents Our future success is highly dependent upon our key personnel, and our ability to attract, retain, and motivate additional qualified personnel.
Even if favorable coverage and reimbursement status is attained for one or more products for which we receive regulatory approval, less favorable coverage policies and reimbursement rates may be implemented in the future. Our future success is highly dependent upon our key personnel, and our ability to attract, retain, and motivate additional qualified personnel.
In particular, because our product candidates are subject to regulation as biological products, we will need to demonstrate that they are safe, pure and potent for use in their target indications. Each product candidate must demonstrate an adequate risk versus benefit profile in its intended patient population and for its intended use.
In particular, because our product candidates are subject to regulation as biological products, 32 Table of Contents we will need to demonstrate that they are safe, pure and potent for use in their target indications. Each product candidate must demonstrate an adequate risk versus benefit profile in its intended patient population and for its intended use.
The IRA also eliminates the "donut hole" under the Medicare Part D program beginning in 2025 by significantly lowering the beneficiary maximum out-of-pocket cost and creating a new manufacturer discount program. It is possible that the ACA will be subject to judicial or Congressional challenges in the future.
The IRA also eliminates the “donut hole” under the Medicare Part D program beginning in 2025 by significantly lowering the beneficiary maximum out-of-pocket cost and creating a new manufacturer discount program. It is possible that the ACA will be subject to judicial or Congressional challenges in the future.
As of December 31, 2022, we had 8.4 million shares of our common stock issued and outstanding (as adjusted for the Reverse Stock Split). Those outstanding shares represent a minority of our authorized shares, meaning that the ownership position of the current stockholders could be diluted significantly were we to issue a large number of additional shares.
As of December 31, 2023, we had 8.9 million shares of our common stock issued and outstanding (as adjusted for the Reverse Stock Split). Those outstanding shares represent a minority of our authorized shares, meaning that the ownership position of the current stockholders could be diluted significantly were we to issue a large number of additional shares.
The timely completion of clinical trials in accordance with their protocols depends, among other things, on our ability to enroll a sufficient number of patients 40 Table of Contents who remain in the study until its conclusion.
The timely completion of clinical trials in accordance with their protocols depends, among other things, on our ability to enroll a sufficient number of patients who remain in the study until its conclusion.
If we or our contract manufacturing organizations, or CMOs, are unable to reliably produce products to specifications acceptable to the FDA or other regulatory authorities, we may not obtain or maintain the approvals we need to commercialize any approved products.
If our contract manufacturing organizations, or CMOs, ,including Cell Ready, are unable to reliably produce products to specifications acceptable to the FDA or other regulatory authorities, we may not obtain or maintain the approvals we need to commercialize any approved products.
In many jurisdictions outside the United States, a product candidate must be approved for reimbursement before it can be approved for sale in that jurisdiction. In some cases, the price that we intend to charge for our products is also subject to approval. 62 Table of Contents We may also submit marketing applications in other countries.
In many jurisdictions outside the United States, a product candidate must be approved for reimbursement before it can be approved for sale in that jurisdiction. In some cases, the price that we intend to charge for our products is also subject to approval. We may also submit marketing applications in other countries.
For example, we previously experienced temporary delays in enrollment due to the COVID-19 pandemic and in satisfying certain FDA requirements for our Phase 2 trial of MT-401 for the treatment of post-transplant AML, and any further delay to our planned timelines for our trial may impact our cost estimates for this trial.
For example, we previously experienced temporary delays in enrollment due to the COVID-19 pandemic and in satisfying certain FDA requirements for our clinical study of MT-401 for the treatment of post-transplant AML, and any further delay to our planned timelines for our trial may impact our cost estimates for this trial.
The Federal Reserve recently raised interest rates multiple times in response to concerns about inflation and is expected to continue to 71 Table of Contents raise rates. Higher interest rates, coupled with reduced government spending and volatility in financial markets, including with respect to foreign exchange, may increase economic uncertainty.
The Federal Reserve recently raised interest rates multiple times in response to concerns about inflation and is expected to continue to raise rates. Higher interest rates, coupled with reduced government spending and volatility in financial markets, including with respect to foreign exchange, may increase economic uncertainty.
To the extent that we sell equity securities or convertible debt securities, your ownership interest will be diluted, and the terms of these securities may include liquidation or other preferences that adversely affect your rights as a common stockholder.
To the extent that we sell equity securities or convertible debt securities, including under the ATM agreement, your ownership interest will be diluted, and the terms of these securities may include liquidation or other preferences that adversely affect your rights as a common stockholder.
The extent to which the COVID-19 pandemic impacts our business and operations, including our clinical development and regulatory efforts, will depend on future developments that are highly uncertain and cannot be predicted with confidence, such as the continued geographic spread of the disease, the duration and effect of any future business disruptions in the United States and other countries to contain and treat patients with the disease.
The extent to which future pandemics impact our business and operations, including our clinical development and regulatory efforts, will depend on future developments that are highly uncertain and cannot be predicted with confidence, such as the continued geographic spread of the disease, the duration and effect of any future business disruptions in the United States and other countries to contain and treat patients with the disease.
Litigation may be necessary to defend against these claims. Even if we are successful in defending against these claims, litigation could result in substantial cost and be a distraction to our management and employees.
Even if we are successful in defending against these claims, litigation could result in substantial cost and be a distraction to our management and employees.
Future or past business transactions (such as acquisitions or integrations) could expose us to additional cybersecurity risks and vulnerabilities, as our systems 69 Table of Contents could be negatively affected by vulnerabilities present in acquired or integrated entities’ systems and technologies.
Future or past business transactions (such as acquisitions or integrations) could expose us to additional cybersecurity risks and vulnerabilities, as our systems could be negatively affected by vulnerabilities present in acquired or integrated entities’ systems and technologies.
We do not intend to pay cash dividends. We have not declared or paid any cash dividends on our common stock, and we do not anticipate declaring or paying cash dividends for the foreseeable future.
We have not declared or paid any cash dividends on our common stock, and we do not anticipate declaring or paying cash dividends for the foreseeable future.
Because our multiTAA-specific T cell therapy-based product candidates are manufactured for each particular patient, we will be required to maintain a chain of identity with respect to the patient’s/donor’s blood cells as it moves from the patient to the manufacturing facility, through the manufacturing process, and back to the patient.
Because our autologous multiTAA-specific T cell therapy-based product candidates, MT-601, is manufactured for each particular patient, we will be required to maintain a chain of identity with respect to the patient’s blood cells as it moves from the patient to the manufacturing facility, through the manufacturing process, and back to the patient.
Without an internal commercial organization or the support of a third party to perform sales and marketing functions, we may be unable to compete successfully against these more established companies. The biotechnology and immunotherapy industries are characterized by rapid technological developments and a high degree of competition. We may be unable to compete with more substantial enterprises.
Without an internal commercial organization or the support of a third - party to perform sales and marketing functions, we may be unable to compete successfully against these more established companies. 44 Table of Contents The biotechnology and immunotherapy industries are characterized by rapid technological developments and a high degree of competition.
In addition, the current military conflict between Russia and Ukraine could disrupt or otherwise adversely impact our operations and those of third parties upon which we rely, although we have not experienced any such disruption to date.
In addition, military conflicts such as between Russia and Ukraine could disrupt or otherwise adversely impact our operations and those of third parties upon which we rely, although we have not experienced any such disruption to date.
Our ongoing and future clinical trials may be also affected by the COVID-19 pandemic. Patient enrollment and clinical site initiation, while ongoing, may be delayed due to prioritization of hospital resources toward the COVID-19 pandemic or other health emergencies, if they arise.
Our ongoing and future clinical trials may be also affected by future pandemics. Patient enrollment and clinical site initiation, while ongoing, may be delayed due to prioritization of hospital resources toward pandemics or other health emergencies, if they arise.
Our manufacturing process is reliant upon specialized equipment, and other specialty materials, which may not be available to us on acceptable terms or at all. For some of this equipment and materials, we rely or may rely on sole-source vendors or a limited number of vendors, which could impair our ability to manufacture and supply our product candidates.
Our manufacturing process is reliant upon specialized equipment, and other specialty materials, which may not be available to us on acceptable terms or at all. We, our vendors, and contract manufacturing organizations rely or may rely on sole-source vendors or a limited number of vendors, which could impair the manufacture and supply of our product candidates.
If we are unable to successfully develop, receive regulatory approval for and commercialize our product candidates, or successfully develop any other product candidates, or experience significant delays in doing so, our business will be harmed. We are early in our development efforts and all of our product candidates are still in clinical development.
Risks Related to the Development of our Product Candidates All of our product candidates are in clinical development. If we are unable to successfully develop, receive regulatory approval for and commercialize our product candidates, or successfully develop any other product candidates, or experience significant delays in doing so, our business will be harmed.
Some patients may not be able to comply with clinical trial protocols if quarantines impede patient movement or interrupt healthcare services. Similarly, we may be unable to recruit and retain patients and principal investigators and site staff who, as healthcare providers, may have heightened exposure to COVID-19, which would adversely impact clinical trial operations.
Some patients may not be able to comply with clinical trial protocols if quarantines impede patient movement 66 Table of Contents or interrupt healthcare services. Similarly, we may be unable to recruit and retain patients and principal investigators and site staff who, as healthcare providers, may have heightened exposure to health epidemics, which would adversely impact clinical trial operations.
Even if our agreements with any future collaborators entitle us to indemnification against losses, such indemnification may not be available or adequate should any claim arise. The multiple roles of certain of Dr. Vera, our Chief Scientific Officer and Chief Operating Officer, could limit his time and availability to us, and create, or appear to create, conflicts of interest. Dr.
Even if our agreements with any future collaborators entitle us to indemnification against losses, such indemnification may not be available or adequate should any claim arise. The multiple roles of Dr. Vera, our President, Chief Executive Officer, and Principal Financial and Accounting Officer, could limit his time and availability to us, and create, or appear to create, conflicts of interest.
Even with an operational facility, our manufacturing capabilities could be affected by cost-overruns, unexpected delays, equipment failures, labor shortages, natural disasters, power failures, transportation difficulties and numerous other factors that could prevent us from fully realizing the intended benefits of our manufacturing strategy and have a material adverse effect on our clinical development and/or commercialization plans.
Additionally, our manufacturing capabilities could be affected by cost-overruns, unexpected delays, equipment failures, labor shortages, natural disasters, power failures, competition with other clients, transportation difficulties and numerous other factors that could prevent us from fully realizing the intended benefits of our manufacturing strategy and have a material adverse effect on our clinical development, commercialization plans and/or general operations.
Our assumptions related to our product candidates, such as with respect to lack of toxicity and manufacturing cost estimates, are based on early limited clinical trials and current manufacturing processes at Baylor College of Medicine, or BCM, and may prove to be incorrect.
Our assumptions related to our product candidates, such as with respect to lack of toxicity and manufacturing cost estimates, are based on early limited clinical trials and current manufacturing processes and may prove to be incorrect.
While we do not believe that any of the patents owned or licensed by us will be found invalid based on these decisions, we cannot predict how future decisions by the courts, the U.S.
While we do not believe that any of the patents owned or licensed by us will be found invalid based on these decisions, we cannot predict how future decisions by the courts, the U.S. Congress or the USPTO may impact the value of our patents.
For example, the complexity and uncertainty of European patent laws have also increased in recent years. In Europe, a new unitary patent system will likely be introduced by the end of 2023, which would significantly impact European patents, including those granted before the introduction of such a system.
For example, the complexity and uncertainty of European patent laws have also increased in recent years. In Europe, a new unitary patent system was introduced by the end of 2023, which significantly impacts European patents, including those granted before the introduction of such a system.
It is possible that governmental and enforcement authorities will conclude that our business practices may not comply with current or future statutes, regulations or case law interpreting applicable fraud and abuse or other healthcare laws and regulations.
Efforts to ensure that our business arrangements comply with applicable healthcare laws may involve substantial costs. It is possible that governmental and enforcement authorities will conclude that our business practices may not comply with current or future statutes, regulations or case law interpreting applicable fraud and abuse or other healthcare laws and regulations.
The manufacture of our product candidates is complex, and we may encounter difficulties in production, particularly with respect to process development or scaling up of our manufacturing capabilities.
The manufacture of our product candidates is complex and we may encounter difficulties in production, particularly with respect to process development.
If we, or any of our third-party suppliers encounter such 44 Table of Contents difficulties, our ability to supply our product candidates for clinical trials, or our product candidates for patients, if approved, could be delayed or stopped, or we may be unable to maintain a commercially viable cost structure.
If any of our third-party suppliers, including Cell Ready, encounter such difficulties, the supply of our product candidates for clinical trials, or our product candidates for patients, if approved, could be delayed or stopped, or we may be unable to maintain a commercially viable cost structure.
Consequently, even if we achieve profitability, we may not be able to utilize a material portion of our net operating loss carryforwards and certain other tax attributes, which could have a material adverse effect on cash flow and results of operations. Catastrophic events may disrupt our business. Our corporate headquarters and cGMP manufacturing facility are located in Houston, Texas.
Consequently, even if we achieve profitability, we may not be able to utilize a material portion of our net operating loss carryforwards and certain other tax attributes, which could have a material adverse effect on cash flow and results of operations. Catastrophic events may disrupt our business.
Our business and operations could be adversely affected by the effects of health epidemics, including the COVID-19 pandemic. Our business and operations could be adversely affected by the effects of health epidemics, including the ongoing COVID-19 virus, which was declared by the World Health Organization as a global pandemic.
Our business and operations could be adversely affected by the effects of health epidemics, including pandemics. Our business and operations could be adversely affected by the effects of health epidemics, as was recently experienced in connection with the COVID-19 virus, which was declared by the World Health Organization as a global pandemic.
In January 2021, the FDA lifted the clinical hold, permitting us to initiate a Phase 2 clinical trial for the treatment of post-transplant AML, with a safety lead-in portion.
In January 2021, the FDA lifted the clinical hold, permitting us to initiate a Phase 2 clinical trial for the treatment of post-transplant AML, with a safety lead-in portion. We completed the safety lead-in portion of the trial in June 2021, and we initiated the remainder of the Phase 2 trial in July 2021.
Depending on the number of patients we ultimately enroll in our trials, and the number of trials we may need to conduct, our overall clinical trial costs may be higher than for more conventional treatments. Further, delays and interruptions to ongoing trials related to the COVID-19 pandemic has increased the duration and costs of such trials.
Depending on the number of patients we ultimately enroll in our trials, and the number of trials we may need to conduct, our overall clinical trial costs may be higher than for more conventional treatments. Further, delays and interruptions to ongoing trials related to global pandemics, as experienced with COVID-19, can increase the duration and costs of such trials.
Accordingly, the regulatory approval pathway for our product candidates may be uncertain, complex, expensive and lengthy, and approval may not be obtained, and the FDA or non-U.S. regulatory authorities may disagree with the design or implementation of our clinical trials or study endpoints.
For example, the FDA has limited experience with commercial development of cell therapies for cancer. Accordingly, the regulatory approval pathway for our product candidates may be uncertain, complex, expensive and lengthy, and approval may not be obtained, and the FDA or non-U.S. regulatory authorities may disagree with the design or implementation of our clinical trials or study endpoints.
The new manufacturing process marks additional manufacturing improvements compared to the processes used in the BCM Phase 1 and 2 trials (36-day manufacturing time) and the current AML trial reflecting the improved manufacturing process (9-day manufacturing time). The new nine-day manufacturing process enables increased antigen specificity and diversity, which has exhibited a strong linear correlation to anti-tumor activity in vitro.
The new manufacturing process marks additional manufacturing 38 Table of Contents improvements compared to the processes used in the BCM Phase 1 and 2 trials (36-day manufacturing time) and our previous AML trial (20-day manufacturing time). The new nine-day manufacturing process enables increased antigen specificity and diversity, which has exhibited a strong linear correlation to anti-tumor activity in vitro.
Until such time, if ever, as we can generate substantial product revenue, we expect to fund our cash requirements through a combination of equity offerings, debt financings and potential collaboration, license and development agreements. We do not currently have a committed external source of funds.
Until such time, if ever, as we can generate substantial product revenue, we expect to fund our cash requirements through a combination of equity offerings, debt financings and potential collaboration, license and development agreements. We do not currently have a committed external source of funds, but have entered into the ATM agreement under which we may sell shares.
We may also experience delays in completing planned clinical trials for a variety of reasons, including delays related to: ● the availability of financial resources to commence and complete the planned trials; ● reaching agreement on acceptable terms with prospective clinical research organizations, or CROs, and clinical trial sites, the terms of which can be subject to extensive negotiation and may vary significantly among different CROs and trial sites; ● obtaining approval by an independent institutional review board, or IRB, at each clinical trial site; ● recruiting suitable patients to participate in a trial; ● having patients complete a trial or return for post-treatment follow-up; ● clinical trial sites deviating from trial protocol or dropping out of a trial; ● adding new clinical trial sites; or ● manufacturing sufficient quantities of qualified materials under cGMPs and applying them on a subject by subject basis for use in clinical trials. 38 Table of Contents Further, the performance of our CROs may also be interrupted by health epidemics or other disruptions, such as the ongoing COVID-19 pandemic, including due to travel or quarantine policies or prioritization of resources toward such health epidemic or disruption.
We may also experience delays in completing planned clinical trials for a variety of reasons, including delays related to: ● the availability of financial resources to commence and complete the planned trials; ● reaching agreement on acceptable terms with prospective clinical research organizations, or CROs, and clinical trial sites, the terms of which can be subject to extensive negotiation and may vary significantly among different CROs and trial sites; ● obtaining approval by an independent institutional review board, or IRB, at each clinical trial site; ● recruiting suitable patients to participate in a trial; ● having patients complete a trial or return for post-treatment follow-up; ● clinical trial sites deviating from trial protocol or dropping out of a trial; ● adding new clinical trial sites; or ● manufacturing sufficient quantities of qualified materials under cGMPs and applying them on a subject by subject basis for use in clinical trials.
An inability to continue to source product from any of these suppliers, which could be due to regulatory actions or requirements affecting the supplier, adverse financial, or other strategic developments experienced by a supplier, labor disputes or shortages, unexpected demands, or quality issues, could adversely affect our ability to satisfy demand for our product candidates, which could adversely and materially affect our operating results or our ability to conduct clinical trials, either of which could significantly harm our business.
An inability to continue to source product from any of these suppliers, which could be due to regulatory actions or requirements affecting the supplier, adverse financial, or other strategic developments experienced by a supplier, labor disputes or shortages, unexpected demands, or quality issues, could adversely affect our ability to satisfy demand for our product candidates, which could adversely and materially affect our operating results or our ability to conduct clinical trials, either of which could significantly harm our business. 37 Table of Contents In the future, we may need to obtain rights to and supplies of specific materials and equipment to be used for the development of our product candidates.
In addition, if the breadth or strength of protection provided by our patents and patent applications is threatened, it could dissuade companies from collaborating with us to license, develop or commercialize current or future product candidates.
In addition, if the breadth or strength of protection provided by our patents and patent applications is threatened, it could dissuade companies from collaborating with us to license, develop or commercialize current or future product candidates. Such a loss of patent protection could have a material adverse impact on our business development.
The FDA has granted orphan drug designation for MT-401 for the treatment of AML after receiving an allogeneic stem cell transplant and for MT-601 for the treatment of patients with pancreatic cancer. We may seek orphan drug designation for other indications or product candidates.
The FDA has granted orphan drug designation for MT-401 for the treatment of AML after receiving an allogeneic stem cell transplant and for MT-601 for the treatment of patients with pancreatic cancer.
We are required, pursuant to Section 404 of the Sarbanes-Oxley Act, or Section 404, to furnish a report by management on, among other things, the effectiveness of our internal control over financial reporting.
We are required, pursuant to Section 404 of the Sarbanes-Oxley Act, or Section 404, to furnish a report by management on, among other things, the effectiveness of our internal control over financial reporting. We are also required to disclose significant changes made in our internal control procedures on a quarterly basis.

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Item 2. Properties

Properties — owned and leased real estate

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Biggest changeITEM 2. PROPERTIES We do not own any real estate or other properties. We lease a manufacturing facility and office space at 4551 Kennedy Commerce Drive, Houston, Texas 77032 on a ten-year agreement from rent commencement date, set to expire in November 2030, which is also our principal business office.
Biggest changeITEM 2. PROPERTIES We do not own any real estate or other properties. We do not directly lease any property but utilize office space through our service agreements with Cell Ready at 9350 Kirby Drive, Suite 300, Houston, Texas 77054, which is also our principal business office. ​
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In April 2020, we entered into a lease for a research facility in Houston, Texas. The lease term is 71 months. ​ ​ 72 Table of Contents

Item 3. Legal Proceedings

Legal Proceedings — active lawsuits and investigations

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Biggest changeOther than as described below, we are not currently a party to any material legal proceedings, and we are not aware of any pending or threatened legal proceeding against us that we believe could have an adverse effect on our business, operating results or financial condition.
Biggest changeOther than as described below, we are not currently a party to any material legal proceedings, and we are not aware of any pending or threatened legal proceeding against us that we believe could have an adverse effect on our business, operating results or financial condition. ​ ITEM 4.
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An arbitration proceeding was brought against the Company before the Financial Industry Regulatory Authority, Inc. (“FINRA”) by a broker seeking to be paid compensation for two financing transactions that occurred in 2018, a warrant conversion and a private placement brokered by another broker.
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MINE SAFETY DISCLOSURE Not Applicable ​ 69 Table of Contents PART II
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The broker’s claims were based on a placement agent agreement for a private placement it brokered in 2017, under which it alleged it was entitled to compensation for the 2018 transactions. The FINRA panel found in favor of the broker and awarded the broker $2.4 million for compensation, interest and attorney fees.
Removed
As of December 31, 2021, the Company recorded an accrual of $2.4 million in accrued liabilities on its consolidated balance sheet and a $2.4 million charge to other expenses. On September 17, 2021, the broker filed a petition to confirm the FINRA arbitration award in the Supreme Court of New York for the County of New York.
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The Company removed the case to the United States District Court for the Southern District of New York on September 27, 2021. On October 22, 2021, the Company filed a motion in federal court to vacate the award.
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On March 9, 2022, the Company was notified that its motion to vacate the award was denied and the broker was awarded an additional $0.1 million in interest. Post judgment interest accrued at 1.02% until the judgment was paid. The Company paid the broker the $2.5 million judgment, which amount included accrued interest, on March 24, 2022.
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On January 3, 2023, the broker was awarded an additional $0.1 million in post-judgment interest, which was recorded to other expenses for the year ended December 31, 2022 and subsequently paid on January 9, 2023. ITEM 4. MINE SAFETY DISCLOSURE Not Applicable ​ 73 Table of Contents PART II

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 We did not record any issuances of unregistered securities during the fourth quarter of 2022. ITEM 6. [RESERVED] ​ 74 Table of Contents
Biggest changeRecent Sales of Unregistered Securities We did not record any issuances of unregistered securities during the fourth quarter of 2023. Issuer Repurchase Of Equity Securities We did not repurchase any equity securities. ITEM 6. [RESERVED] ​ 70 Table of Contents
ITEM 5. MARKET FOR REGISTRANT’S COMMON EQUITY, RELATED STOCKHOLDER MATTERS AND ISSUER PURCHASES OF EQUITY SECURITIES Market Information Our common stock is listed for trading on the Nasdaq Capital Market under the symbol “MRKR”. As of March 1, 2023, we had 174 stockholders of record whom are holding shares.
ITEM 5. MARKET FOR REGISTRANT’S COMMON EQUITY, RELATED STOCKHOLDER MATTERS AND ISSUER PURCHASES OF EQUITY SECURITIES Market Information Our common stock is listed for trading on the Nasdaq Capital Market under the symbol “MRKR”. As of March 18, 2024, we had 36 stockholders of record, whom are holding shares.
The price of our common stock on March 1, 2023 was $2.05 per share. Dividend Policy No dividends have been declared or paid on our common stock. We have incurred recurring losses and do not currently intend to pay any cash dividends in the foreseeable future.
The price of our common stock on March 18, 2024 was $4.43 per share. Dividend Policy No dividends have been declared or paid on our common stock. We have incurred recurring losses and do not currently intend to pay any cash dividends in the foreseeable future.

Item 7. Management's Discussion & Analysis

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

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Biggest changeThe following table sets forth our cash, cash equivalents and restricted cash and working capital as of December 31, 2022 and 2021: ​ ​ ​ ​ ​ ​ ​ ​ ​ December 31, December 31, ​ ​ 2022 ​ 2021 Cash, cash equivalents and restricted cash ​ $ 11,782,000 ​ $ 43,497,000 Working capital ​ $ 8,837,000 ​ $ 33,081,000 ​ Cash Flows The following table summarizes our cash flows for the years ended December 31, 2022 and 2021: ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ For the Years Ended ​ ​ December 31, ​ 2022 2021 Net cash provided by (used in): ​ ​ Operating activities ​ $ (26,972,000) ​ $ (27,280,000) Investing activities ​ (4,945,000) ​ (3,131,000) Financing activities ​ 202,000 ​ 52,556,000 Net (decrease) increase in cash, cash equivalents and restricted cash ​ $ (31,715,000) ​ $ 22,145,000 ​ Operating Activities Net cash used in operating activities during the year ended December 31, 2022 was $27.0 million.
Biggest changeWe have financed our operations primarily through public and private offerings of our stock and debt including warrants and the exercise thereof, grants, and more recently through the cash proceeds received from the Cell Ready transaction and additional grants to fund research. 75 Table of Contents The following table sets forth our cash and cash equivalents and working capital as of December 31, 2023 and 2022: ​ ​ ​ ​ ​ ​ ​ ​ December 31, 2023 December 31, 2022 Cash and cash equivalents ​ $ 15,111,000 ​ $ 11,782,000 Working capital ​ $ 14,053,000 ​ $ 8,837,000 ​ Cash Flows The following table summarizes our cash flows for the years ended December 31, 2023 and 2022: ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ For the Years Ended ​ ​ December 31, ​ 2023 2022 Continuing operations: ​ ​ ​ ​ ​ ​ Net cash used in operating activities $ (10,341,000) $ (21,513,000) Net cash provided by financing activities ​ ​ 1,105,000 ​ ​ 202,000 Discontinued operations ​ ​ ​ ​ ​ ​ Net cash used in operating activities ​ (6,099,000) ​ (5,459,000) Net cash provided by (used in) investing activities ​ $ 18,664,000 ​ $ (4,945,000) Net increase (decrease) in cash and cash equivalents ​ $ 3,329,000 ​ $ (31,715,000) ​ Continuing Operations Operating Activities Net cash used in operating activities from continuing operations during the year ended December 31, 2023 was $10.3 million.
In August 2021, we received notice of a Product Development Research award totaling approximately $13.1 million from the Cancer Prevention and Research Institute of Texas, or CPRIT, to support our Phase 2 clinical trial of MT-401. During the years ended December 31, 2022 and 2021, respectively, we recognized $3.4 million and $1.2 million of revenue associated with the CPRIT grant.
In August 2021, we received notice of a Product Development Research award totaling approximately $13.1 million from the Cancer Prevention and Research Institute of Texas, or CPRIT, to support our Phase 2 clinical trial of MT-401. During the years ended December 31, 2023 and 2022, respectively, we recognized $2.7 million and $3.4 million of revenue associated with the CPRIT grant.
On January 24, 2023, our board of directors approved the filing of a certificate of amendment to our amended and restated certificate of incorporation (the “Amendment”) with the Secretary of State of the State of Delaware to affect the one-for-ten (1:10) Reverse Stock Split of our outstanding common stock and a reduction in the total number of authorized shares of our common stock from 300,000,000 to 30,000,000 (the “Shares Reduction”).
Reverse Stock Split On January 24, 2023, our board of directors approved the filing of a certificate of amendment to our amended and restated certificate of incorporation (the “Amendment”) with the Secretary of State of the State of Delaware to effect the one-for-ten (1:10) Reverse Stock Split of our outstanding common stock and a reduction in the total number of authorized shares of our common stock from 300,000,000 to 30,000,000 (the “Shares Reduction”).
Costs and timing of clinical trials and development of our product candidates will depend on a variety of factors that include, but are not limited to, the following: ● per patient clinical trial costs; ● the number of patients that participate in the clinical trials; ● the number of sites included in the clinical trials; ● the length of time required to enroll eligible patients; ● the number of doses that patients receive; ● the drop-out or discontinuation rates of patients; ● potential additional safety monitoring or other studies requested by regulatory agencies; ● the duration of patient follow-up; ● the efficacy and safety profile of the product candidates; and 76 Table of Contents ● the ability to successfully manufacture patient doses.
Costs and timing of clinical trials and development of our product candidates will depend on a variety of factors that include, but are not limited to, the following: ● per patient clinical trial costs; ● the number of patients that participate in the clinical trials; ● the number of sites included in the clinical trials; ● the length of time required to enroll eligible patients; ● the number of doses that patients receive; ● the drop-out or discontinuation rates of patients; ● potential additional safety monitoring or other studies requested by regulatory agencies; ● the duration of patient follow-up; ● the efficacy and safety profile of the product candidates; and ● the ability to successfully manufacture patient doses.
The primary objectives of the adjuvant arm of the trial are to evaluate relapse-free survival after MT-401 treatment when compared with a randomized control group. Through the date of this filing, the Company has received $4.8 million of funds from the CPRIT grant.
The primary objectives of the adjuvant arm of the trial are to evaluate relapse-free survival after MT-401 treatment when compared with a randomized control group. Through the date of this filing, the Company has received $6.8 million of funds from the CPRIT grant.
MANAGEMENT’S DISCUSSION AND ANALYSIS OF FINANCIAL CONDITION AND RESULTS OF OPERATIONS The following discussion of our financial condition, changes in financial condition, plan of operations and results of operations should be read in conjunction with (i) our audited consolidated financial statements as of December 31, 2022 and December 31, 2021 and (ii) the section entitled “Business”, included in this annual report.
MANAGEMENT’S DISCUSSION AND ANALYSIS OF FINANCIAL CONDITION AND RESULTS OF OPERATIONS The following discussion of our financial condition, changes in financial condition, plan of operations and results of operations should be read in conjunction with (i) our audited consolidated financial statements as of December 31, 2023 and December 31, 2022 and (ii) the section entitled “Business”, included in this annual report.
We do not believe that inflation has had a material impact on our results of operations for the periods presented, except with respect to payroll-related costs and other costs arising from or related to government-imposed regulations. ITEM 7A.
We do not believe that inflation has had a material impact on our results of operations for the periods presented, except with respect to payroll-related costs and other costs arising from or related to government-imposed regulations.
The incurrence of indebtedness would result in increased fixed payment obligations and could involve certain restrictive covenants, such as limitations on our ability to incur additional debt, limitations on our ability to acquire or license intellectual property rights and other operating restrictions that could adversely impact 82 Table of Contents our ability to conduct our business.
The incurrence of indebtedness would result in increased fixed payment obligations and could involve certain restrictive covenants, such as limitations on our ability to incur additional debt, limitations on our ability to acquire or license intellectual property rights and other operating restrictions that could adversely impact our ability to conduct our business.
The broker’s claims were based on a placement agent agreement for a private placement it brokered in 79 Table of Contents 2017, under which it alleged it was entitled to compensation for the 2018 transactions. The FINRA panel found in favor of the broker and awarded the broker $2.4 million for compensation, interest and attorney fees.
The broker’s claims were based on a placement agent agreement for a private placement it brokered in 2017, under which it alleged it was entitled to compensation for the 2018 transactions. The FINRA panel found in favor of the broker and awarded the broker $2.4 million for compensation, interest and attorney fees.
The Sales Agents will be entitled to compensation under the Sales Agreement at a commission rate equal to 3.0% of the gross sales price per share sold under the ATM Agreement, and we have provided each of the Sales Agents with indemnification and contribution rights.
The Sales Agents will be entitled to compensation under the Sales Agreement at a commission 78 Table of Contents rate equal to 3.0% of the gross sales price per share sold under the ATM Agreement, and we have provided each of the Sales Agents with indemnification and contribution rights.
We have based this estimate on assumptions that may prove to be wrong, and we could utilize our available capital resources sooner than we currently expect. Furthermore, our operating plan may change, and we may need additional funds sooner than planned in order to meet operational needs and capital requirements for product development and commercialization.
We have based this estimate on assumptions that may prove to be wrong, and we could utilize our available capital resources sooner than we currently expect. Furthermore, our operating plan may change, and we may need additional funds sooner than planned in order to meet operational needs and capital requirements for 77 Table of Contents product development and commercialization.
FINANCIAL STATEMENTS The Financial Statements are incorporated herein by reference to pages F-1 to F-25 at the end of this report and the supplementary data is not applicable. ITEM 9. CHANGES IN AND DISAGREEMENTS WITH ACCOUNTANTS ON ACCOUNTING AND FINANCIAL DISCLOSURE We have had no changes in, or disagreements with our principal independent accountants. 86 Table of Contents
FINANCIAL STATEMENTS The Financial Statements are incorporated herein by reference to pages beginning on page F-1 at the end of this report and the supplementary data is not applicable. ITEM 9. CHANGES IN AND DISAGREEMENTS WITH ACCOUNTANTS ON ACCOUNTING AND FINANCIAL DISCLOSURE We have had no changes in, or disagreements with our principal independent accountants. 83 Table of Contents
Net Loss The decrease in our net loss during the year ended December 31, 2022 compared to the year ended December 31, 2021 was due to higher grant income and related party service revenue, cost reductions in our research and development activities and moderate stabilization of our clinical trial activities.
Net Loss from continuing operations The decrease in our net loss from continuing operations during the year ended December 31, 2023 compared to the year ended December 31, 2022 was due to higher grant income and related party service revenue, cost reductions in our research and development activities and moderate stabilization of our clinical trial activities.
Interest Income Interest income was $0.2 million and $6,000 for the years ended December 31, 2022 and 2021, respectively, and was attributable to interest income relating to funds that are held in U.S. Treasury notes and U.S. government agency-backed securities.
Interest Income Interest income was $0.5 million and $0.2 million for the years ended December 31, 2023 and 2022, respectively, and was attributable to interest income relating to funds that are held in U.S. Treasury notes and U.S. government agency-backed securities.
In January 2023, the Company received $2.4 million from CPRIT. ​ On September 13, 2022, the Company received notice from the FDA that it had awarded the Company a $2.0 million grant from the FDA’s Orphan Products Grant program to support the Company’s Phase 2 clinical trial of MT-401 for the treatment of post-transplant AML.
In September 2022, the Company received notice from the FDA that it had awarded the Company a $2.0 million grant from the FDA’s Orphan Products Grant program to support the Company’s Phase 2 clinical trial of MT-401 for the treatment of post-transplant AML.
We base our estimates on historical experience and on various other assumptions that we believe to be reasonable under 83 Table of Contents the circumstances, the results of which form the basis for making judgments about the carrying values of assets and liabilities and the reported amounts of expenses that are not readily apparent from other sources.
We base our estimates on historical experience and on various other assumptions that we believe to be reasonable under the circumstances, the results of which form the basis for making judgments about the carrying values of assets and liabilities and the reported amounts of expenses that are not readily apparent from other sources. Actual results could differ from those estimates.
The Company estimates the fair value of stock options granted using the Black-Scholes option pricing model. The Black-Scholes option pricing model was developed for use in estimating the fair value of traded options, which have no vesting restrictions and are fully transferable.
The Black-Scholes option pricing model was developed for use in estimating the fair value of traded options, which have no vesting restrictions and are fully transferable.
The state net operating loss carryforwards of $21.9 million, if not utilized, will begin to expire in 2035. The state net operating loss carryforwards of $16.6 million generated in 2018 and thereafter are subject to an 80% limitation on taxable income, do not expire and will carry forward indefinitely.
The federal net operating loss carryforwards of $93.8 million generated in 2018 and thereafter are subject to an 80% limitation on taxable income, do not expire and will carry forward indefinitely. The state net operating loss carryforwards of $21.7 million, if not utilized, will begin to expire in 2035.
At December 31, 2022 and 2021, we recorded a 100% valuation allowance against our deferred tax assets of approximately $41.4 million and $36.4 million, respectively, as our management believes it is uncertain that they will be fully realized.
At December 31, 2023 and 2022, we recorded a 100% valuation allowance against our deferred tax assets of approximately $39.7 million and $41.3 million, respectively, as our management believes it is uncertain that they will be fully realized.
Treasury zero-coupon issues with an equivalent remaining term. 84 Table of Contents Expected Dividend — The Company has never declared or paid any cash dividends on its common shares and does not plan to pay cash dividends in the foreseeable future, and, therefore, uses an expected dividend yield of zero in its valuation models. ​ The Company amortizes the fair value of the awards expected to vest on a straight-line basis over the requisite service period of the awards.
Expected Dividend — The Company has never declared or paid any cash dividends on its common shares and does not plan to pay cash dividends in the foreseeable future, and, therefore, uses an expected dividend yield of zero in its valuation models. ​ The Company amortizes the fair value of the awards expected to vest on a straight-line basis over the requisite service period of the awards.
Property and Equipment Leasehold improvements, furniture, equipment and software are recorded at cost and are depreciated using the straight-line method over the estimated useful lives of the related assets, which range from three to five years. Leasehold improvements are amortized over the shorter of the estimated useful life or the remaining lease term.
Property and Equipment Leasehold improvements, furniture, equipment and software are recorded at cost and are depreciated using the straight-line method over the estimated useful lives of the related assets, which range from three to five years.
Pursuant to the Amendment, at the effective time of the Amendment, every ten (10) shares of our issued and outstanding common stock was automatically combined into one (1) issued and outstanding share of common stock and the authorized shares of our common stock was reduce from 300,000,000 to 30,000,000, without any change in par value per share.
Eastern Time on January 26, 2023. 71 Table of Contents ​ Pursuant to the Amendment, at the effective time of the Amendment, every ten (10) shares of our issued and outstanding common stock was automatically combined into one (1) issued and outstanding share of common stock and the authorized shares of our common stock was reduced from 300,000,000 to 30,000,000, without any change in par value per share.
On September 13, 2022, we received notice from the FDA that we had been awarded a $2.0 million grant from the FDA’s Orphan Products Grant program to support our Phase 2 clinical trial of MT-401 for the treatment of post-transplant AML. During the year ended December 31, 2022, we recognized $0.1 million of revenue associated with the FDA grant.
On September 13, 2022, we received notice from the FDA that we had been awarded a $2.0 million grant from the FDA’s Orphan Products Grant program to support our Phase 2 clinical trial of MT-401 for the treatment of post-transplant AML.
Purchases of property and equipment for the year ended December 31, 2022 were predominantly comprised of laboratory equipment along with $0.1 million of computers, software and equipment and $0.1 million of furniture and fixtures. $3.5 million of purchases in construction in progress related to a second modular cleanroom and the continued buildout of our manufacturing facility.
Net cash used in investing activities from discontinued operations was $4.9 million for the year ended December 31, 2022. $1.3 million in purchases of property and equipment for the year ended December 31, 2022 were comprised of laboratory equipment along with $0.1 million of computers, software and equipment and $0.1 million of furniture and fixtures. $3.5 million of purchases in construction in progress related to a second modular cleanroom and the continued buildout of our former manufacturing facility.
When infused into a cancer patient, the multiTAA-specific T cells are designed to kill cancer cells expressing the TAA targets and potentially recruit the patient’s immune system to participate in the cancer killing process. We licensed the underlying technology for multiTAA-specific T cell therapy from BCM in March 2018. BCM had utilized the therapy in seven exploratory clinical trials.
When infused into a patient with cancer, the multiTAA-specific T cells are designed to kill cancer cells expressing the TAA and potentially recruit the patient’s immune system to participate in the cancer killing process. We licensed the underlying technology for multiTAA-specific T cell therapy from Baylor College of Medicine, or BCM, in March 2018.
During the year ended December 31, 2022, we sold 60,651 shares of our common stock under the ATM Agreement for net proceeds of $0.2 million.
During the year ended December 31, 2023, we sold 265,334 shares of our common stock under the ATM Agreement for proceeds of $1.0 million. During the year ended December 31, 2022, we sold 60,651 shares of our common stock under the ATM agreement for proceeds of $202,100.
Based on our revised clinical and research and development plans and our revised timing expectations related to the progress of our programs, we expect that our cash and cash equivalents as of December 31, 2022 will enable us to fund our operating expenses and capital expenditure requirements into the third quarter of 2023.
Based on our clinical plans and our timing expectations related to the progress of our programs, we expect that, together with drawdowns of available grant funds, our cash and cash equivalents as of December 31, 2023 will enable us to fund our operating expenses and capital expenditure requirements into the fourth quarter of 2025.
The Company recorded $0.1 million of grant income related to the FDA grant as revenue for the year ended December 31, 2022 and at December 31, 2022, the Company recorded $0.1 million of grant income receivable. On March 13, 2023, the Company received $0.1 million of funds from the FDA grant.
The Company recorded $0.4 million of grant income related to the FDA grant as revenue for the year ended December 31, 2023 and at December 31, 2023, the Company recorded $0.3 million of grant income receivable. In February 2024, the Company received $0.3 million of funds from the FDA grant.
Any shares of our common stock sold will be issued pursuant to our shelf registration statement on Form S-3 (File No. 333-258687), which the SEC declared effective on August 19, 2021; however, our use of the shelf registration statement on Form S-3 will be limited for so long as we are subject to General Instruction I.B.6 of Form S-3, which limits the amounts that we may sell under the registration statement and in accordance with the ATM agreement.
However, our use of the shelf registration statement on Form S-3 will be limited for so long as we are subject to General Instruction I.B.6 of Form S-3, which limits the amounts that we may sell under the registration statement and in accordance with the ATM agreement.
The Company recorded $0.1 million of grant income related to the FDA grant as revenue for the year ended December 31, 2022 and at December 31, 2022, the Company recorded $0.1 million of grant income receivable. On March 13, 2023, the Company received $0.1 million of funds from the FDA grant.
The Company recorded $0.2 million of grant income related to the SBIR grant as revenue for the year ended December 31, 2023 and at December 31, 2023, the Company recorded $0.2 million of grant income receivable. In February 2024, the Company received $0.2 million of funds from the SBIR grant.
Grant Income is recognized when the related costs are incurred. Restricted cash received from grants in advance of incurring qualifying costs is recorded as deferred revenue and recognized as revenue when qualifying costs are incurred. Qualifying grant income earned in advance of cash received from grants is recognized as revenue and recorded as other receivable.
Qualifying grant income earned in advance of cash received from grants is recognized as revenue and recorded as other receivable.
In accordance with ASC 730-20-25-8, the financial risk associated with the research and development has been transferred to CPRIT, because repayment of the grant depends solely on the results of research and development having future economic benefit. The Company accounts for this arrangement as a contract to perform research and development for others and applies ASC 606 by analogy.
The Company determined that the CPRIT Contract is not in the scope of ASC 808 or ASC 606. In accordance with ASC 730-20-25-8, the financial risk associated with the research and development has been transferred to CPRIT, because repayment of the grant depends solely on the results of research and development having future economic benefit.
Liquidity and Capital Resources We have not generated any revenues from the sales or licensing of our product candidates since inception and only have limited revenue associated with grants. We have financed our operations primarily through public and private offerings of our stock and debt including warrants and the exercise thereof.
Liquidity and Capital Resources We have not generated any revenues from the sales or licensing of our product candidates since inception and only have limited revenue associated with grants to fund research.
General and Administrative Expenses General and administrative expenses decreased by 1% to $12.8 million for the year ended December 31, 2022 from $12.9 million during the prior period.
General and Administrative Expenses General and administrative expenses decreased by 34% to $7.5 million for the year ended December 31, 2023 from $11.3 million during the prior period.
Clinical and research and development expenses consist of expenses incurred in performing research and development activities, cost of our clinical trials, including compensation, share-based compensation expense and benefits for research and development employees and consultants, facilities expenses, overhead expenses, cost of supplies, manufacturing expenses, fees paid to third parties and other outside expenses. Clinical costs are expensed as incurred.
Financial Overview Research and Development Expenses Our research and development expenses are primarily costs associated with our clinical trials, including compensation, share-based compensation expense and benefits for employees and selected consultants, manufacturing expenses and fees paid to third parties. Clinical costs are expensed as incurred.
Financing Activities Net cash provided by financing activities was $0.2 million and $52.6 million during the years ended December 31, 2022 and 2021, respectively. primarily due to the net proceeds received from sales from the ATM Agreement (as defined below) in 2022 and the underwritten public offering in 2021.
Financing Activities Net cash provided by financing activities was $1.1 million and $0.2 million during the years ended December 31, 2023 and 2022, respectively, primarily due to the net proceeds received from sale of common stock through the ATM Agreement as well as the exercise of stock options.
The Company recognizes grant income when amounts eligible for reimbursement are determinable and have been incurred, the applicable conditions under the grant arrangements have been met, and collectability of amounts due is reasonably assured or already received. The classification of costs incurred related to grants is based on the nature of the activities performed by the Company.
The Company accounts for this arrangement as a contract to perform research and development for others and applies ASC 606 by analogy. The Company recognizes grant income when amounts eligible for reimbursement are determinable and have been incurred, the applicable conditions under the grant arrangements have been met, and collectability of amounts due is reasonably assured or already received.
In August 2021, we received notice of a Product Development Research award totaling approximately $13.1 million from CPRIT to support our Phase 2 clinical trial of MT-401. The Company determined that the CPRIT Contract is not in the scope of ASC 808 or ASC 606.
For grant and awards outside the scope of ASC 808, the Company applies ASC 606 by analogy, and revenue is recognized when the Company incurs expenses related to the grants for the amount the Company is entitled to under the provisions of the contract. 80 Table of Contents In August 2021, we received notice of a Product Development Research award totaling approximately $13.1 million from CPRIT to support our Phase 2 clinical trial of MT-401.
The purchase agreement does not exhibit any of the characteristics for liability classification under ASC Topic 480, Distinguishing Liabilities from Equity. During the year ended December 31, 2022, we did not sell any shares of our stock under the Purchase Agreement.
The purchase agreement does not exhibit any of the characteristics for liability classification under ASC Topic 480, Distinguishing Liabilities from Equity. During the year ended December 31, 2023, we sold 12,500 shares of our stock under the Purchase Agreement. In January 2023, Lincoln Park was issued 180,410 shares of stock as a commitment fee at a value of $0.5 million.
The use of cash primarily related to our net loss of $29.9 million and a $5.8 million decrease from changes in assets and liabilities.
The use of cash primarily related to our net loss from continuing operations of $19.8 million and a $4.7 million decrease from changes in assets and liabilities. This decrease was partially offset by $3.3 million of stock-based compensation.
Significant changes and expenditures in operating expenses are outlined as follows: Research and Development Expense Research and development expenses decreased by 6% to $26.1 million for the year ended December 31, 2022, compared to $27.8 million for the year ended December 31, 2021.
Significant changes and expenditures in operating expenses are outlined as follows: Research and Development Expense Research and development expenses or clinical trial costs decreased by 13% to $10.4 million for the year ended December 31, 2023, compared to $12.0 million for the year ended December 31, 2022, mainly as a result of the Cell Ready transaction.
Any change in ownership greater than 50% under Section 382 of the Internal Revenue Code places significant annual limitations on the use of such net operating loss carryforwards.
The state net operating loss carryforwards of $16.6 million generated in 2018 and thereafter are subject to an 80% limitation on taxable income, do not expire and will carry forward indefinitely. Any change in ownership greater than 50% under Section 382 of the Internal Revenue Code places significant annual limitations on the use of such net operating loss carryforwards.
In these studies, BCM treated over 150 patients suffering from a variety of cancers including lymphoma, multiple myeloma, acute myeloid leukemia, acute lymphoblastic leukemia, pancreatic cancer, breast cancer and various sarcomas. In those studies, BCM saw evidence of clinical benefit, expansion of infused cells, epitope spreading, and decreased toxicity compared to other cellular therapies.
BCM had utilized the therapy in seven exploratory clinical trials. In these studies, BCM treated over 150 patients suffering from a variety of cancers including lymphoma, multiple myeloma, acute myeloid leukemia, or AML, acute lymphoblastic leukemia, or ALL, pancreatic cancer, breast cancer and various sarcomas.
These factors raise substantial doubt regarding our ability to continue as a going concern within one year after the date that the financial statements are issued. Our consolidated financial statements have been prepared on a going concern basis, which implies that we will continue to realize our assets and discharge our liabilities in the normal course of business.
However, our ability to pursue our longer term planned business activities is dependent upon our successful efforts to raise additional capital and obtain grant funding. Our consolidated financial statements have been prepared on a going concern basis, which implies that we will continue to realize our assets and discharge our liabilities in the normal course of business.
Off-Balance Sheet Arrangements We have not entered into any off-balance sheet arrangements that have or are reasonably likely to have a current or future effect on our financial condition, changes in financial condition, revenues, expenses, results of operations, liquidity, capital expenditures or capital resources that is material to investors. 85 Table of Contents Tax Loss and Credit Carryforwards As of December 31, 2022, we have approximately $135.2 million of federal and $38.5 million of state net operating loss carryforwards that may be available to offset future taxable income, if any.
We do not expect the adoption of this guidance to have a material impact on its consolidated financial statements. 81 Table of Contents Off-Balance Sheet Arrangements We have not entered into any off-balance sheet arrangements that have or are reasonably likely to have a current or future effect on our financial condition, changes in financial condition, revenues, expenses, results of operations, liquidity, capital expenditures or capital resources that is material to investors.
If we are unable to raise capital when needed or on attractive terms, we could be forced to delay, reduce or eliminate our research and development programs or future commercialization efforts. On March 16, 2021, the Company issued an aggregate of 3,228,286 shares of its common stock, for net proceeds of $52.6 million, pursuant to an underwritten public offering.
If we are unable to raise capital when needed or on attractive terms, we could be forced to delay, reduce or eliminate our research and development programs or future commercialization efforts.
During the fourth quarter of 2021, the Company received $2.4 million advancement of funds in relation to the CPRIT grant. The Company recorded $3.4 million of grant income related to the CPRIT grant as revenue for the year ended December 31, 2022.
The Company recorded $2.7 million of grant income related to the CPRIT grant as revenue for the year ended December 31, 2023 and at December 31, 2023, the Company recorded $0.5 million of grant income receivable.
The use of cash primarily related to our net loss of $41.9 million and a $5.5 million increase from changes in assets and liabilities. This was in addition to $6.0 million of stock-based compensation, $2.1 million of depreciation expense and $1.0 million of right-of-use asset amortization and lease liability accretion.
The use of cash primarily related to our net loss from continuing operations of $14.0 million, partially offset by a $2.8 million increase from changes in assets and liabilities and $0.9 million of stock-based compensation. Net cash used in operating activities from continuing operations during the year ended December 31, 2022 was $21.5 million.
We anticipate our research and development costs will continue to increase over the next several years due to increased spending on the clinical development and manufacturing of our product candidates.
We anticipate our clinical trial costs will continue to increase over the next several years due to increased spending on the clinical development and manufacturing of our product candidates. ​ 72 Table of Contents General and Administrative Expenses General and administrative expenses consist primarily of personnel costs, including share-based compensation, legal fees relating to patent and corporate matters, insurance costs, consulting and professional fees, audit and investor relations.
During the year ended December 31, 2022, we recognized $5.5 million of revenue associated with the Services agreement. Operating Expenses Operating expenses incurred during the fiscal year ended December 31, 2022 were $39.0 million compared to $40.7 million in the prior year.
Operating expenses incurred during the fiscal year ended December 31, 2023 were $17.9 million compared to $23.3 million in the prior year.
Results of Operations For the Years Ended December 31, 2022 and 2021 The following table summarizes the results of our operations (rounded to the thousand except for per share amounts) for the years ended December 31, 2022 and 2021, together with the changes to those items: ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ For the Years Ended ​ ​ ​ ​ ​ ​ ​ ​ December 31, ​ ​ ​ ​ ​ 2022 2021 Change Revenues: ​ ​ ​ ​ ​ Grant income ​ $ 3,514,000 ​ $ 1,242,000 ​ $ 2,272,000 183 % Related party service revenue ​ ​ 5,500,000 ​ ​ — ​ ​ 5,500,000 ​ 100 % Total revenues ​ 9,014,000 ​ 1,242,000 ​ 7,772,000 626 % Operating expenses: ​ ​ ​ ​ ​ ​ ​ Research and development ​ 26,139,000 ​ 27,795,000 ​ (1,656,000) (6) % General and administrative ​ 12,820,000 ​ 12,925,000 ​ (105,000) (1) % Total operating expenses ​ 38,959,000 ​ 40,720,000 ​ (1,761,000) (4) % Loss from operations ​ (29,946,000) ​ (39,478,000) ​ 9,532,000 (24) % Other income (expense): ​ ​ ​ ​ ​ ​ ​ ​ Arbitration settlement ​ ​ (233,000) ​ ​ (2,407,000) ​ ​ 2,174,000 ​ (90) % Interest income ​ 248,000 ​ 6,000 ​ 242,000 4,033 % Net loss ​ $ (29,931,000) ​ $ (41,879,000) ​ $ 11,948,000 (29) % ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Net loss per share, basic and diluted ​ $ (3.58) ​ $ (5.47) ​ $ 1.89 (35) % Weighted average number of common shares outstanding ​ 8,351,000 ​ 7,651,000 ​ 700,000 9 % ​ 77 Table of Contents Revenue We did not generate any revenue during the years ended December 31, 2022 and 2021, respectively, from the sales or licensing of our product candidates.
Results of Operations For the Years Ended December 31, 2023 and 2022 The following table summarizes the results of our continuing operations (rounded to the thousand except for per share amounts) for the years ended December 31, 2023 and 2022, together with the changes to those items: ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ For the Years Ended ​ ​ ​ ​ ​ ​ ​ ​ December 31, ​ ​ ​ ​ ​ 2023 2022 Change Revenues: ​ ​ ​ ​ ​ Grant income ​ $ 3,311,000 ​ $ 3,514,000 ​ $ (203,000) (6) % Total revenues ​ 3,311,000 ​ 3,514,000 ​ (203,000) (6) % Operating expenses: ​ ​ ​ ​ ​ ​ ​ Research and development ​ 10,417,000 ​ 11,968,000 ​ (1,551,000) (13) % General and administrative ​ 7,476,000 ​ 11,336,000 ​ (3,860,000) (34) % Total operating expenses ​ 17,893,000 ​ 23,304,000 ​ (5,411,000) (23) % Loss from operations ​ (14,582,000) ​ (19,790,000) ​ 5,208,000 (26) % Other income (expenses): ​ ​ ​ ​ ​ ​ ​ ​ Arbitration settlement ​ ​ — ​ ​ (233,000) ​ ​ 233,000 ​ (100) % Interest income ​ 539,000 ​ 248,000 ​ 291,000 117 % Loss from continuing operations before income taxes ​ ​ (14,042,000) ​ ​ (19,775,000) ​ ​ 5,733,000 ​ (29) % ​ Revenue We did not generate any revenue during the years ended December 31, 2023 and 2022, respectively, from the sales or licensing of our product candidates.
The decrease in general and administrative expenses of $0.1 million mainly comprised the following: o increase of $0.6 million in severance expense related to headcount reductions, o increase of $0.5 million in advisory and professional fees, o increase of $0.1 million in other general and administrative expenses, offset by o decrease of $0.1 million in other headcount-related expenses, o decrease of $0.5 million in stock-based compensation, o decrease of $0.4 million in rent and utility expenses, in part due to the termination of our office lease at 3200 Southwest Freeway, Suite 2500 in Houston, and o decrease of $0.3 million in recruiting expenses.
The decrease in general and administrative expenses of $3.8 million mainly comprised the following: ● decrease of $3.2 million in headcount-related expenses, including stock-based compensation expense and net of severance expense, ● decrease of $0.6 million in rent and utilities expense, primarily as a result of the Cell Ready transaction, including its assumption of facility leases, ● decrease of $0.6 million in legal and professional fees, ● decrease of $0.2 million in insurance expense, offset by ● increase of $0.8 million in consulting expenses.
Other Income (Expense) Other income (expense), net consists of interest income and arbitration settlement expenses.
Income Taxes We recognized $4,000 in state tax expense for the year ended December 31, 2023 and none for the year ended December 31, 2022. Other Income (Expense) Other income (expense), net consists of interest income and arbitration settlement expenses.
The decrease of $1.7 million in 2022 was primarily attributable to the following: o decrease of $1.7 million in sponsored research and consulting expenses from BCM agreements, o decrease of $1.4 million in process development expenses, o decrease of $0.6 million in technology licensing fees due to termination of Mayo license agreements, described below, o decrease of $0.3 million in consulting expenses, o decrease of $0.2 million in stock-based compensation expenses, offset by o increase of $1.5 million in headcount-related expenses as we increased the number of research and development personnel, o increase of $0.7 million in depreciation expense due to increased capital investments, and o increase of $0.3 million in vaccine-based clinical trial expenses related to the termination of the Mayo license agreements, described below.
The decrease of $1.6 million in 2023 was primarily attributable to the following: ● decrease of $2.1 million in process development expenses, ● decrease of $0.8 million in AML Phase 2 clinical trial expenses, offset by ● increase of $1.3 million in Cell Ready (outsourced) clinical manufacturing costs and process development expenses.
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We are advancing three product candidates as part of our multiTAA-specific T cell program for: 1. autologous treatment of lymphoma, and selected solid tumors 2. allogeneic T cells for the treatment of acute myeloid leukemia, or AML 3. off-the-shelf products in various indications Our current clinical development programs are: ● MT-401 for the treatment of post-transplant AML, currently in a Phase 2 clinical trial ● MT-401-OTS for the treatment of AML, for which we expect to dose the first patient in a Phase 2 clinical trial in 2023 ● MT-601 for the treatment of pancreatic cancer, for which we have a cleared IND from the FDA to initiate a Phase 1 trial in the fourth quarter of 2023 ​ ● MT-601 for the treatment of lymphoma, for which we have a cleared IND from the FDA and initiated a Phase 1 trial in the first quarter of 2023 We believe that the simplicity of our manufacturing process allows additional modifications to expand multiTAA-specific T cell recognition of cancer targets.
Added
In those studies, BCM saw evidence of clinical benefit, expansion of infused cells, and decreased toxicity compared to other cellular therapies.
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For example, we are currently analyzing the potential for a 12-antigen multiTAA-specific T cell therapy and assessing the potential for combination therapies for our multiTAA-specific T cell products. We have positioned ourselves to be in full control of our research and development and clinical manufacturing needs by establishing a fully validated, FDA registered, manufacturing facility.
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We are advancing two product candidates for 3 clinical indications as part of our multiTAA-specific T cell program for: ● Autologous multiTAA product for the treatment of lymphoma and pancreatic cancer (MT-601) ● Off-the-Shelf (OTS) product in various indications (e.g., MT-401-OTS) We do not genetically engineer our multiTAA-specific T cell therapies and we believe that our product candidates are superior to T cells engineered with chimeric antigen receptors, or CAR-T, for several reasons including: ● Multiple targets → enhanced tumoricidal effect→ minimized tumor immune escape ​ ● Clinical safety → no treatment-related side effects, including cytokine release syndrome (CRS) or other severe adverse effects (SAEs), were attributed to the use of multiTAA-specific T cell therapies to date ​ ● Non-genetically engineered T cell products → no risk of mutagenesis and reduced manufacturing complexity → lower cost For these reasons, we believe our endogenous T cell receptor-based therapies may provide meaningful clinical benefit and safety to patients with both hematological and solid tumors.
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We believe that this has key advantages that distinguish us from our competitors, particularly because we are less reliant on contract manufacturing organizations, which are expensive and often have long lead times, shortages of skilled labor and a backlog of customers. 75 Table of Contents Reverse Stock Split On May 24, 2022, we held our annual meeting of stockholders at which our stockholders approved a proposal to effect an amendment to our certificate of incorporation, as amended, to implement a reverse stock split at a ratio within a range between and including one-for three (1:3) and one-for-twelve (1:12) and a corresponding reduction in the total number of authorized shares of our common stock.
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We believe that the simplicity of our manufacturing process allows additional modifications to expand multiTAA-specific T cell recognition of cancer targets. For example, we are assessing the potential of combining multiTAA-specific T cell products with other products.
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The Amendment became effective at 5:00 p.m. Eastern Time on January 26, 2023.
Added
During the years ended December 31, 2023 and 2022, we recognized $0.4 million and $0.1 million of revenue associated with the FDA grant, respectively. 73 Table of Contents In May 2023, we received notice of a $2.0 million grant from the National Institutes of Health Small Business Innovation Research (“SBIR”) program to support the development and investigation of MT-401 for the treatment of AML patients following standard-of-care therapy with hypomethylating agents.
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Financial Overview Research and Development Expenses To date, our research and development expenses have related primarily to the development of our clinical platform and the identification and development of our product candidates.
Added
During the year ended December 31, 2023, we recognized $0.2 million of revenue associated with the SBIR grant. All funding agencies have agreed to continue their financial support and to shift funds to the MT-401-OTS program. Operating Expenses Operating expenses incurred during the fiscal year ended December 31, 2023 were $17.9 million compared to $23.3 million in the prior year.
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General and Administrative Expenses General and administrative expenses consist primarily of salaries and other related costs, including share-based compensation, for personnel in executive, finance, accounting, business development, legal and human resources functions.
Added
In 2023, the Company implemented changes to its organizational structure due to the transaction with Cell Ready and to reduce operational costs. In connection with these changes, the Company reduced headcount, including the separation of its former Chief Executive Officer, Peter Hoang, in May 2023 and its former Chief Accounting Officer, Michael Loiacono, in June 2023.
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Other significant costs include facility costs not otherwise included in research and development expenses, legal fees relating to patent and corporate matters, insurance costs and professional fees for consultancy, accounting, audit and investor relations.
Added
During the second quarter of 2023, the Company recorded $0.9 million of severance and termination-related costs. The payments of these costs were completed in July of 2023. Effective May 1, 2023, the Company’s board of directors appointed Dr.
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We anticipate that our general and administrative expenses will increase in the future to support our continued research and development activities, and the potential commercialization of our product candidates. Income Taxes We did not recognize any income tax expense for the years ended December 31, 2022 and 2021.
Added
Juan Vera as the Company’s President and Chief Executive Officer. 74 Table of Contents Effective June 30, 2023, the board of directors appointed Eliot M. Lurier as the Company’s Interim Chief Financial Officer, whereby Mr.
Removed
In April 2022, we entered into a binding services agreement, or the Service Agreement, with Wilson Wolf. Pursuant to the Services Agreement, Wilson Wolf made a cash payment to us in the amount of $8.0 million, as consideration for certain training and research services.
Added
Lurier provided consulting services to the Company pursuant to a consulting between the Company and Danforth Advisors, LLC (“Danforth”) and received no compensation directly from the Company. On November 17, 2023, the Company terminated the consulting agreement between the Company and Danforth, effective January 16, 2024. On November 17, 2023, Mr.
Removed
Included in research and development expenses are expenses related to agreements with BCM. In November 2018 and February 2020, we entered in Sponsored Research Agreements with BCM, which provided for the conduct of research for us by credentialed personnel at BCM’s Center for Cell and Gene Therapy.
Added
Lurier ceased serving as the Company’s Interim Chief Financial Officer and Dr. Vera was appointed as the Company’s Principal Financial and Accounting Officer.
Removed
During the years ended December 31, 2022 and 2021, we incurred $0 and $0.03 million of expenses related to these agreements, respectively. 78 Table of Contents In September 2019, we entered in a Clinical Supply Agreement with BCM, which provided for BCM to provide to us multi tumor antigen specific products.
Added
Discontinued Operations Operating Activities Net cash used in operating activities from discontinued operations during the year ended December 31, 2023 was $6.1 million, which primarily related to our net loss from discontinued operations of $3.0 million, which is net of $2.5 million in revenue for which cash had been received in the prior period.
Removed
During the years ended December 31, 2022 and 2021, we incurred $0.7 million and $1.2 million related to this agreement, respectively. In October 2019, we entered in a Workforce Grant Agreement with BCM, which provided for BCM to provide to us manpower costs of projects for manufacturing, quality control testing and validation run activities.
Added
Net cash used in operating activities from discontinued operations during the year ended December 31, 2022 was $5.5 million, which primarily related to our net loss from discontinued operations of $10.2 million, partially offset by cash received in advance of related party revenue recorded. 76 Table of Contents Investing Activities Net cash provided by investing activities from discontinued operations for the year ended December 31, 2023 was $18.7 million primarily due to the proceeds from the Cell Ready transaction, net of transaction costs.
Removed
During the years ended December 31, 2022 and 2021, we incurred $0.4 million and $1.1 million related to this agreement, respectively. In August 2020, we entered in a Clinical Trial Agreement with BCM, which provided for BCM to provide to us investigator-initiated research studies.
Added
In May 2023, the Company announced that it had received a $2.0 million grant from the National Institutes of Health Small Business Innovation Research (“SBIR”) program to support the development and investigation of MT-401 for the treatment of AML patients following standard-of-care therapy with hypomethylating agents.

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