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Item 1. Business

2023-03-22 compared with 2022-03-17 · 93 added, 247 removed, 625 unchanged (35% of the section changed)

We are a clinical-stage immuno-oncology company specializing in the development and commercialization of novel T cell-based immunotherapies and innovative peptide-based vaccines for the treatment of hematological malignancies and solid tumor indications.

We are a clinical-stage immuno-oncology company specializing in the development and commercialization of novel T cell-based immunotherapies for the treatment of hematological malignancies and solid tumor indications.

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.

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.

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.

BCM had utilized the therapy in seven exploratory clinical trials.

In these studies, BCM treated over 150 patients suffering from a variety of cancer indications including lymphoma, multiple myeloma, acute myeloid leukemia, or AML, acute lymphoblastic leukemia, or ALL, pancreatic cancer, breast cancer and various sarcomas.

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.

In those studies, BCM saw evidence of clinical benefit, expansion of infused cells epitope spreading, and decreased toxicity compared to other cellular therapies.

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autologous treatment of lymphoma, and selected solid tumors

allogeneic T cells for the treatment of acute myeloid leukemia, or AML

allogeneic T cells for the treatment of AML

off-the-shelf products in various indications

Because we do not genetically engineer our MultiTAA-specific T cell therapies, we believe that our product candidates are superior to T cells engineered with chimeric antigen receptors, or CAR-T, for several reasons including:

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

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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.

We are also developing innovative peptide-based immunotherapeutic vaccines for the treatment of metastatic solid tumors.

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 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 manufacturing facility.

For example, we are currently analyzing the potential for a 12-antigen multiTAA-specific T cell therapy.

We are also assessing the potential of combining multiTAA-specific T cell products with other 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.

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.

Company-Sponsored Clinical Development of Multi-TAA Specific T Cell Therapies

MT-401 for the Treatment of Post-Transplant AML

We are pursuing post-transplant AML as the lead indication for our first company-sponsored MultiTAA-specific T cell program.

● In April 2020, 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 after receiving an allogeneic hematopoietic stem cell transplant, or HSCT.

We are pursuing post-transplant AML as the lead indication for our first company-sponsored multiTAA-specific T cell program in the ARTEMIS study.

We submitted an investigational new drug, or IND, application to the FDA, to conduct a Phase 2 clinical trial of multiTAA-specific T cell therapy, which we refer to as MT-401 (zedenoleucel), in post-allogeneic HSCT patients with AML in both the adjuvant and active disease setting.

The dose administered in this multicenter trial is currently 200 million cells every two weeks for three doses.

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 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%].

● 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

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:

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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.

We submitted an investigational new drug, or IND, application to the FDA, to conduct a Phase 2 clinical trial of MultiTAA-specific T cell therapy, which we refer to as MT-401 (zedenoleucel), in post-allogeneic HSCT patients with AML in both the adjuvant and active disease setting.

The dose administered in this multicenter trial is currently 100 million cells every two weeks for three doses.

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.

We have completed the safety lead-in portion of the trial in June 2021 and enrolled six patients with active disease:

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 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.

● 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.

Correlative studies showed that the patient saw significant expansion of infused multiTAA-specific T cells in addition to extensive epitope spreading.

● We initiated the remainder of the Phase 2 trial in July 2021 and have completed enrollment of approximately 20 patients, and we expect to report results from the active disease arm of the trial in the second quarter of 2022.

We began manufacturing MT-401 for the Phase 2 trial at our cGMP manufacturing facility in the fourth quarter of 2021.

There were no objective responses from the frank relapse patients.

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.

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).

This new process enabled a >90% reduction in the number of operator interventions during production and an improved final T cell product candidate compared to the original product candidate used in the ARTEMIS trial.

These process improvements have yielded an MT-401 product candidate that has five times the measurable specificity and four times the potency in terms of tumor killing as compared to the prior manufacturing process.

We have now treated 12 patients with MT-401 manufactured using our improved manufacturing process, with 16 patients treated with MT-401 manufactured using the original process, for a total of 28 patients.

● After completing the safety lead-in portion, we initiated the remainder of the Phase 2 trial in July 2021, in which we intend to enroll 210 patients at approximately 20 transplant centers.

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.

To date, a total of 11 patients in the adjuvant arm of the ARTEMIS study have been randomized to treatment with MT-401 using a new manufacturing process or to standard-of-care.

All patients are too early for evaluation, but the Data Monitoring Committee has reviewed the existing safety data and has not identified any concerns.

A total of four MRD+ patients have been treated and are currently evaluable.

Two MRD+ patients were treated with MT-401 manufactured using the original manufacturing process and showed elimination of detectable disease.

Two additional MRD+ patients were treated with MT-401 manufactured used in the improved process.

● The first MRD+ patient was treated at 100 x 106 cells per infusion and was able to remain in stable disease for six months, allowing the patient to bridge to a second allogeneic transplant.

● The second MRD+ patient was dosed at 200 x 106 cells per infusion and the PCR value, which proved to be a valuable tool for detecting MRD, has decreased by 70% only four weeks after the last infusion.

This patient’s disease status will continue to be closely monitored and evaluated.

● A fifth MRD+ patient has been treated with MT-401 manufactured used in the improved process but is too early for evaluation.

Additional MRD+ patients have been enrolled and are awaiting treatment.

● We anticipate reporting a data readout of the MRD+ patient subset in the second half of 2023.

To date, a total of 15 frank relapse patients have been treated.

In addition to the 11 patients previously reported, who were treated with MT-401 manufactured using the original manufacturing process, four additional patients have been treated with MT-401 manufactured using the improved manufacturing process.

● Of the four patients treated with the improved manufacturing process, one of these patients received a dose of 100 x 106 cells per infusion, while the other three patients were dosed at 200 x 106 cells per infusion.

● None of the frank relapse patients showed an objective response to therapy.

● We have suspended further enrollment of frank relapse patients while re-evaluating additional modifications for this patient cohort, including potentially higher cell doses.

In September 2022, we announced that we had been awarded 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 minimal residual disease in post-transplant AML after allogeneic stem cell transplant.

Off-the-shelf MT-401 (MT-401-OTS) for the Treatment of AML

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We believe our off-the-shelf platform has high scalability, where one donor has the potential to provide more than 100 patient products.

Our open IND for MT-401 for the treatment of AML includes approval of an off-the-shelf program.

Our open IND for MT-401 for the treatment of AML includes clearance of the protocol that will test the safety and efficacy of the off the shelf product in patients with AML/MDS who cannot access their HSCT donor.

We are in the process of developing our patient cell bank inventory and expect to dose the first patient in 2023.

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In January 2022, the FDA granted orphan drug designation to MT-601 for the treatment of patients with pancreatic cancer.

We plan to submit an

IND to the FDA in 2022 to initiate a Phase 1 multicenter clinical trial in 2023 in locally advanced, unresectable or metastatic pancreatic cancer to assess the safety and clinical efficacy of MT-601 in combination with front-line chemotherapy.

We expect to enroll a total of approximately 40 patients and anticipate this trial will include both an antigen/dose escalation portion followed by a dose expansion portion, with a dose of 20 - 100 million cells every four weeks for up to six doses.

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.

We expect to initiate the PANACEA study by the fourth quarter of 2023 and to enroll a total of approximately 40 patients.

The PANACEA trial will include a dose escalation portion followed by a dose expansion portion, with a dose of 200 - 400 million cells every four weeks for up to six doses.

MT-601 for the Treatment of Lymphoma

We are also pursuing the development of MT-601 for the treatment of lymphoma, and we plan to submit an IND to the FDA in 2022 to initiate a Phase 1 clinical trial in 2023.

We are also pursuing the development of MT-601 for the treatment of lymphoma.

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.

The Phase 1 clinical trial, named APOLLO study, was initiated in the first quarter of 2023, and we anticipate reporting a clinical readout in the first quarter of 2024.

Additional Clinical Development of multiTAA-Specific T Cell Therapies

We are also evaluating the MultiTAA-specific T cell therapies in a Phase 2 clinical trial for the treatment of breast cancer and in Phase 1 clinical trials for the treatment of ALL, lymphoma, MM and sarcoma, all of which are being conducted by BCM.

As of June 2021, the MultiTAA-specific T cell therapies have been generally well tolerated by all of the patients enrolled in clinical trials in hematological and solid tumor indications with no incidents of cytokine release syndrome or neurotoxicity, which are frequently associated with CAR-T therapies.

We are also evaluating the multiTAA-specific T cell therapies in a Phase 2 clinical trial for the treatment of breast cancer and in Phase 1 clinical trials for the treatment of ALL, lymphoma, multiple myeloma, or MM, and sarcoma, all of which are being conducted by BCM.

As of June 2021, the multiTAA-specific T cell therapies were generally well tolerated by all of the patients enrolled in clinical trials in hematological and solid tumor indications with no incidents of cytokine release syndrome or neurotoxicity, which are frequently associated with CAR-T therapies.

Our ongoing clinical trials may be also affected by the COVID-19 pandemic and the emergence of any new variant strains of COVID-19.

Based on our observations in clinical trials in AML, pancreatic cancer, lymphoma, ALL and MM, we believe that the multiTAA-specific T cell therapies have the potential to mediate a meaningful anti-tumor effect, as well as significant in vivo expansion of T cells.

We may initiate additional clinical trials investigating other indications in addition to our planned Phase 2 trial in post-transplant AML patients.

Our clinical-stage pipeline, including clinical trials being conducted by BCM and other partners, is set forth below:

Clinical Program Updates

Initial Safety Lead-In Results from Phase 2 Clinical Trial of MT-401 (zedenoleucel) for the Treatment of Post-Transplant AML

In February 2022, we announced the initial results of the safety lead-in portion of our Phase 2 clinical trial of MT-401.

Three patients were dosed with MT-401 manufactured with the legacy reagent used in the Phase 1 trial, and three patients were dosed with MT-401 manufactured using a new reagent from an alternative supplier.

We anticipate using this supplier for clinical and commercial manufacturing of MT-401.

We completed the safety lead-in portion of the trial in June 2021.

The safety lead-in enrolled six patients with active disease:

one MRD positive patient and five frank relapse patients.

The initial results from the safety lead-in are as follows:

● no dose limiting toxicities, cytokine release syndrome or neurotoxicity were observed.

The results were consistent with the safety data observed in more than 150 patients treated in the Phase 1/2 studies at the Baylor College of Medicine;

● one MRD+ patient became MRD- after infusion with MT-401;

● no objective responses from the frank relapse patients;

● Immuno-monitoring data indicate evidence of epitope spreading after infusion of MT-401 in the patient who converted from MRD+ to MRD-.

We initiated the remainder of the Phase 2 trial in July 2021 and have completed enrollment of approximately 20 patients, and we expect to report results from the active disease arm of the trial in the second quarter of 2022.

Our multiTAA-specific T cells are designed to enhance the capacity of non-engineered T cells to find and kill cancer by increasing the diversity and quantity of naturally occurring cancer killing T cells within the patient.

Our goal is to be the leader in the development and commercialization of transformative immunotherapies for the treatment of hematological malignancies and solid tumors.

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.

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.

The key elements of our strategy include:

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We are pursuing post-transplant AML as the lead indication for the multiTAA-specific T cell program.

We completed the safety lead-in portion of our Phase 2 trial in post-transplant AML in June 2021 and initiated the remainder of the Phase 2 trial in July 2021.

We completed the safety lead-in portion of our Phase 2 trial of MT-401 in post-transplant AML in June 2021 and initiated the remainder of the Phase 2 trial in July 2021.

We initiated a Phase 1 trial of MT-601 in non-Hodgkin lymphoma in the first quarter of 2023.

We plan to initiate future additional clinical trials in other tumor types based on emerging data.

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If data from these early clinical trials are positive, we will consider the therapeutic and commercial potential for such therapies to be advanced as new product candidates for us.

In addition, we plan to use BCM facilities and our company laboratories to enable the process development required to support the Phase 2 clinical trials of our product candidates.

In addition, we plan to use our company laboratories to enable the process development required to support the Phase 2 clinical trials of our product candidates.

We have invested, and plan to continue to invest in our own research and development and chemistry, manufacturing and controls, or CMC, capabilities to enhance our ability to conduct process development to optimize our manufacturing process, product quality and commercial scalability.

For instance, we developed and are implementing a new nine-day MultiTAA-specific T cell manufacturing process for our current Phase 2 AML trial as well as future clinical trials using a patient-specific manufacturing approach.

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 (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.

The new process produces a patient product that is four times more potent, with the potential to greatly improve tumor killing.

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.

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.

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Our world-renowned scientific founders and scientific advisors have made seminal contributions to major discoveries in the field of immuno-oncology, and have significant experience in oncology, immunology and cell therapy.

We intend to significantly leverage the knowledge, experience and advice of our scientific founders and advisors, as well as the institutional expertise of BCM, the Mayo Foundation and our other major institutional partners, to advance our therapies through the clinic and into commercialization.

We are in the process of evaluating the peptide vaccine therapeutic products and programs to determine the future strategy and the proper allocation of our resources to best maximize stockholder value.

In conjunction with this evaluation process we may de-emphasize or terminate certain vaccine therapeutic products or programs.

Such strategic review and evaluations are a priority and an important part of our ongoing operations.

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.

Background and History of Cancer Immunotherapies

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Autologous multiTAA-specific T cell therapies target the NY-ESO-1, PRAME, MAGE-A4, Survivin and SSX2 antigens.

We recently reported updated clinical data from BCM’s Phase 1/2 clinical trial of the autologous MultiTAA therapy for the treatment of patients with pancreatic cancer, and we are currently evaluating these therapies for the treatment of patients with lymphoma, MM and other selected solid tumors in Phase 1 trials.

We recently reported updated clinical data from BCM’s Phase 1/2 clinical trial of the autologous multiTAA therapy for the treatment of patients with pancreatic cancer, and we are currently evaluating these therapies for the treatment of patients with lymphoma, pancreatic and other selected solid tumors in Phase 1 trials.

Allogeneic multiTAA-specific T cell therapies target the WT1, NY-ESO-1, PRAME, and Survivin antigens.

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· Non-gene modified.

Unlike CAR and TCR-based approaches, our 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.

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.

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· Low incidence rate of adverse events.

As of January 2022, the MultiTAA-specific T cell therapy has been 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 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.

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.

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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.

Company-Sponsored Clinical Development of Our MultiTAA-Specific T Cell Therapies

MT-401 for the Treatment of Post-Transplant AML

We are conducting a Phase 2 clinical trial in post-allogeneic HSCT patients with AML in both the adjuvant and active disease setting under our IND, and this trial may become pivotal pending the results of the interim analysis.

The dose administered in this multicenter trial is currently 100 million cells every two weeks for three doses.

In the adjuvant setting, patients will be randomized to either MT-401 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.

We completed the safety lead-in portion of the trial in June 2021 that enrolled six patients.

Three patients were dosed with MT-401 manufactured using the legacy reagent used in the Phase 1 trial, and three patients were dosed with MT-401 manufactured using a reagent from an alternative supplier.

We anticipate using this supplier for clinical and commercial supply of MT-401.

The safety lead-in enrolled six patients with active disease:

one MRD positive patient and five frank relapse patients.

The initial results from the safety lead-in are as follows:

● no dose limiting toxicities, cytokine release syndrome or neurotoxicity were observed.

The results were consistent with the safety data observed in more than 150 patients treated in the Phase 1/2 studies at the Baylor College of Medicine;

● one MRD+ patient became MRD- after infusion with MT-401;

● no objective responses from the frank relapse patients;

● immuno-monitoring data indicate evidence of epitope spreading after infusion of MT-401 in the patient who converted from MRD+ to MRD-.

After completing the safety lead-in portion, we initiated the remainder of the Phase 2 trial in July 2021, in which we intend to enroll 180 patients at approximately 20 transplant centers.

Group 1 will comprise of 120 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.

We have completed enrollment of approximately 20 patients, and we expect to report results from the active disease arm of the trial in the second quarter of 2022.

MT-601 for the Treatment of Pancreatic Cancer

We are developing MT-601 for the treatment of pancreatic cancer.

MT-601 is a MultiTAA-specific T cell product targeting six tumor-associated antigens that are highly expressed in pancreatic cancer.

In January 2022, the FDA granted orphan drug designation to MT-601 for the treatment of patients with pancreatic cancer.

We plan to submit an IND to the FDA in 2022 to initiate a Phase 1 multicenter clinical trial in 2023 in locally advanced, unresectable or metastatic pancreatic cancer to assess the safety and initial efficacy of MT-601 in combination with front-line chemotherapy.

We expect to enroll a total of approximately 40 patients and anticipate this trial will include both an antigen/dose escalation portion followed by a dose expansion portion, with a dose of between 20 and 100 million cells every four weeks for up to six doses.

MT-601 for the Treatment of Lymphoma

We are also pursuing the development of MT-601 for the treatment of lymphoma, and we plan to submit an IND to the FDA in 2022 to initiate a Phase 1 clinical trial in 2023.

Off-the-Shelf Platform

We intend to expand our AML program with the development of MT-401-OTS, a scalable, off-the-shelf product candidate with the potential to match patients to treatment in under three days.

We intend to dose patients using “banked” products based on human leukocyte antigen matching.

We believe our off-the-shelf platform has high scalability, where one donor has the potential to provide more than 100 patient products.

Our open IND for MT-401 for the treatment of AML includes approval of an off-the-shelf program.

We are in the process of developing our patient cell bank inventory and expect to dose the first patient in 2023.

We expect to expand our off-the-shelf platform into clinical trials for other hematological malignancies and solid tumors.

Clinical Development of Our multiTAA-Specific T Cell Therapies by BCM

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● Out of the 13 evaluable patients (best overall response):

o 4 patients experienced objective responses after administration of MultiTAA cells;

o 1 patient experienced a radiographic complete response occurring at month 9 after starting chemotherapy;

o 3 patients experienced partial responses per RECIST occurring at 6-9 months after starting chemotherapy;

o 6 patients experienced stable disease;

o 1 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 9 of the 13 patients exceeding historical control of overall survival;

● 5 patients enrolled in the study were not administered MultiTAA-specific T cells, either because of disease progression (4 patients) which made them ineligible for treatment, or because insufficient starting material from the patient was available for manufacturing (1 patient);

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;

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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.

The G-Rex is a cell culture device manufactured by Wilson Wolf used by many cell therapy developers, both in commercial and academic settings.

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.

The device allows a user to introduce cells, medium and other reagents into a cell culture chamber, which has a gas-permeable membrane at its bottom.

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Upon release of the final patient product, the cells are frozen and transported to the site where the cells will be administered.

The standard dose for patients with lymphoma, AML or myeloma ranges from 5 to 20 million cells per meter squared (corresponding to typical doses of 10 to 40 million cells per adult patient).

The standard dose for patients with lymphoma, AML or myeloma ranges from five to 20 million cells per meter squared (corresponding to typical doses of 10 to 40 million cells per adult patient).

These cell doses represent a significantly smaller dose of cells, when compared to CAR-T or TCR therapies.

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We believe that our in-house manufacturing facility confers key advantages that distinguish us from our competitors, in particular that 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.

Our Peptide-Based Immunotherapeutic Vaccines:

TPIV200 and TPIV100/110

In addition to our MultiTAA-specific T cell therapies, we are developing peptide-based immunotherapeutic vaccines that are designed to precisely target breast and ovarian cancer cells, in contrast to standard therapies for the treatment of cancer that target both cancer cells and normal cells.

Our peptide vaccines are derived from naturally processed T cell-targeted antigens.

We believe that our peptide vaccines are potentially effective standalone therapies but may also enhance the efficacy of other immunotherapy approaches, including our own MultiTAA-specific T cell therapies.

Our multipeptide approach is fundamentally different from traditional vaccine therapies that have generally targeted a major histocompatibility complex, or MHC, class I-restricted epitope and have historically performed poorly as stand-alone treatments.

We are currently evaluating TPIV200 for the treatment of breast cancers that overexpress FRa in multiple Phase 2 clinical trials and TPIV100 for the treatment of breast cancers that overexpress HER2/neu in Phase 1b and Phase 2 clinical trials.

In conjunction with this evaluation process we may de-emphasize or terminate certain vaccine therapeutic products or programs.

Such strategic review and evaluations are a priority and an important part of our ongoing operations.

TPIV200 for the Treatment of FRa-Overexpressed Breast and Ovarian Cancers

FRa is overexpressed in over 80% of breast cancers and over 90% of ovarian cancers.

The only treatment options for these cancers are surgery, radiation therapy and chemotherapy, creating a very important and urgent clinical need for a new therapeutic strategy.

Time to recurrence is relatively short for ovarian cancer and survival prognosis is extremely poor after recurrence.

In the United States alone, every year there are 22,350 new ovarian cancer diagnoses and 268,600 new breast cancer diagnoses, of which 10% are diagnoses of triple-negative breast cancer.

TPIV200 is composed of a mixture of five FRa-derived immunogenic peptides adjuvanted with low-dose granulocyte-macrophage colony-stimulating factor, or GM-CSF, and is designed to activate both the CD4 + and CD8 + T cell compartments in order to activate a patient’s T cells against the targets.

Recent developments in immunology suggest that both CD4 + and CD8 + activation support a robust immune response.

Clinical Development

Phase 1 Clinical Trial in Advanced Breast and Ovarian Cancer

In this Phase 1 clinical trial, completed by Mayo Clinic in 2015, 21 patients with advanced breast or ovarian cancer who had undergone standard surgery and adjuvant treatment were treated with one cycle of cyclophosphamide, followed by intradermal vaccination of TPIV200 on day one of a 28-day cycle for a maximum of six vaccination cycles.

In the trial, 20 of 21 patients generated T cell responses.

These responses developed slowly over the course of the vaccination cycles, with a median time to maximal immunity of five months.

Over 90% of patients developed robust and durable antigen-specific immune responses against FRa without regard for HLA type, which aligns with the intended mechanism of action of the vaccine, and 89% of the patients responded to multiple epitopes included in the TPIV200 vaccine, with most patients demonstrating T cell immunity to three or more epitopes.

Further, all 16 patients in the observation stage generated T cell responses that lasted over six months.

TPIV200 was well-tolerated, with only one Grade 3 drug-related adverse event.

In a two-year patient follow-up analysis, the 10 enrolled ovarian cancer patients had longer median progression-free survival time of 528 days than the 313 days historically reported for the standard-of-care chemotherapy treatment.

All patients were alive at the final follow-up.

None of the 7 breast cancer patients had experienced a recurrence.

Phase 2 Clinical Trials in Triple-Negative Breast Cancer

Triple-negative breast cancer is one of the most difficult cancers to treat and represents a clear unmet medical need.

With the support of a $13.3 million grant from the Department of Defense, the Mayo Foundation is conducting a 280-patient Phase 2 clinical trial of TPIV200 in patients with triple-negative breast cancer, which began enrolling patients in late 2017 and is still recruiting patients.

On June 21, 2016, we announced the initiation of a randomized four-arm Phase 2 trial of TPIV200 for the treatment of patients with Stage 1 to Stage 3 triple-negative breast cancer who have completed initial surgery and chemo/radiation therapy.

This open-label, 80-patient clinical trial is designed to evaluate dosing regimens, pre-treatment, efficacy and immune responses.

In the trial, we are evaluating a high dose and a low dose of TPIV200, each of which will be tested both with and without cyclophosphamide prior to vaccination.

To date, there have been no drug-related serious adverse events reported.

The last subject completed the trial in July 2021 and the data analysis and clinical study report are being prepared.

Phase 2 Clinical Trial in Combination With Durvalumab for Patients with Ovarian Cancer

On April 21, 2016, we announced our participation in an ovarian cancer trial sponsored by Memorial Sloan Kettering Cancer Center, or MSKCC, in collaboration with AstraZeneca Pharmaceuticals in ovarian cancer patients who are not responsive to platinum, a commonly used chemotherapy for ovarian cancer.

This open-label Phase 2 trial of TPIV200 in 40 patients is designed to evaluate the effects of combination therapy with AstraZeneca’s checkpoint inhibitor durvalumab (anti-PD-L1).

Interim results from the first 27 patients were presented at the AACR-Rivkin Symposium in September 2018;

safety of the combination was shown in these heavily pretreated patients and a subset of patients exhibited durable disease stabilization.

Objective response rate and progression-free survival with combination treatment was not superior from the expected efficacy of durvalumab as a monotherapy.

However, post-immunotherapy follow-up was suggestive of improved clinical benefit from standard therapies, as the majority of patients’ post-progression went on to receive subsequent standard therapy with durable clinical benefit, creating a rationale for exploration of these agents in combination with chemotherapy.

Although we have no business relationship with AstraZeneca, we paid for half of the costs of this trial, in addition to providing TPIV200.

TPIV 100/110 for the Treatment of HER2/neu-Overexpressed Breast Cancers

HER2/neu amplification/overexpression results in an effective therapeutic target in breast and gastric cancer.

Over-expressed HER2 is detected predominantly in malignancies of epithelial origin, such as breast, gastric, esophageal, colorectal, salivary gland, pancreatic,

epithelial ovarian, endometrial, and bladder carcinomas, as well as gallbladder and extrahepatic cholangiocarcinomas.

HER2 is over-expressed in approximately 25% of breast cancers and its expression is associated with unfavorable pathologic features and aggressive disease if not treated with targeted therapies, relative to other forms of breast cancer.

While the outcome of patients with HER2 positive breast cancer has significantly improved in the past few decades with an advent of anti-HER2 therapies, a substantial number of resected patients with all types of breast cancer subsequently develop metastatic disease.

The continued prevalence of these cancers represents a high unmet medical need, justifying the targeted development of immunotherapeutic strategies.

We have added a MHC class I-restricted peptide, which we licensed from the Mayo Foundation on April 16, 2012, to the four MHC class II-restricted peptides present in TPIV100, resulting in TPIV 110 after the five peptides are mixed with GM-CSF.

We have amended the existing IND to incorporate the fifth peptide and will use TPIV110 in future trials with the goal of producing an even more robust vaccine activating both CD4 + (helper) and CD8 + (killer) T cells.

On June 7, 2016, we announced that we had exercised our option agreement with Mayo Foundation and signed a worldwide license agreement to TPIV100.

The license gives us the right to develop and commercialize the technology in any cancer indication in which the HER2/neu antigen is overexpressed.

As part of this agreement, the IND for the HER2/neu Phase 1 trial was transferred from Mayo Foundation to us for Phase 2 clinical trials of TPIV100.

See “—Mayo Foundation for Medical Education and Research Relationships—Mayo HER2/neu License.”

Clinical Development

Phase 1 Clinical Trials in HER2/neu + Breast Cancer

In the Phase 1 trial of 20 patients conducted at the Mayo Clinic, TPIV100 was well tolerated.

Nineteen of the twenty evaluable patients showed robust T-cell immune responses to the antigens in the vaccine.

An additional secondary endpoint incorporated into this trial was a two-year follow-on recording the time to disease recurrence in the participating breast cancer patients.

On March 14, 2017, we announced that our partners at the Mayo Clinic received a $3.8 million grant from the Department of Defense to conduct a Phase 1b trial of TPIV100 in ductal carcinoma in situ, or DCIS, an early form of breast cancer.

We are working closely with the Mayo Foundation on this clinical trial by providing clinical and manufacturing expertise, as well as providing GMP vaccine formulations under contract.

The trial is expected to enroll 40 – 45 women with DCIS and commenced such enrollment during the first quarter of 2019.

If the trial is successful and subject to receiving marketing approval from the FDA, we believe that TPIV100 may eventually augment or even replace standard surgery and chemotherapy, and potentially could become part of a routine immunization schedule for preventing breast cancer in healthy women.

Phase 2 Clinical Trials in HER2/neu + Breast Cancer

On October 10, 2018, we announced that the Mayo Clinic had been awarded a grant of $11 million from the Department of Defense intended to cover the costs of a large randomized, double-blind Phase 2 trial of TPIV100.

We are working closely with the Mayo Foundation on this clinical trial by providing clinical and manufacturing expertise, as well as providing GMP vaccine formulations under contract.

In this trial, 190 patients will be randomized, in a 2:1 fashion, to receive TPIV100 plus maintenance ado-trastuzumab emtansine, or T-DM1, or maintenance T-DM1with placebo plus GM-CSF.

The trial will evaluate whether the administration of vaccine during T-DM1 maintenance therapy in patients with residual disease post-neoadjuvant chemotherapy effectively blocks disease recurrence and the development of metastatic breast cancer.

By prevention of recurrence and metastasis, the expectation is that mortality associated with breast cancer will be decreased.

Manufacturing

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Establishing and managing the supply chain requires a significant financial commitment and the creation and maintenance of numerous third-party contractual relationships.

Third-party manufacturers supply us with raw materials for the peptide vaccines, and other third-party manufacturers convert these raw materials into API or convert the API into final dosage form.

For most of our peptide vaccine candidates, once our raw materials are produced, we rely on different third parties to manufacture the API, to make finished drug product and to lyophilize, package and label the finished product.

While we currently have focused on single vendors for manufacturing of peptide, formulation development, and lyophilization and vialing, we have access to numerous other vendors, if required.

Our drug discovery, development and ultimate commercialization activities face, and will continue to face, intense competition from organizations such as pharmaceutical and biotechnology companies, as well as academic and research institutions and government agencies.

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Our product candidates may compete with product candidates from a number of companies, which are developing various types of similar in vivo T-cell immunotherapies and therapeutic cancer vaccines to treat cancer, including:

Advaxis Inc., Merck/Immune Design, Celldex, BN Immunotherapeutics, Immunocellular, SELLAS Life Sciences Group, Inc.

(formerly) Galena BioPharma, NuGenerex Immuno-Oncology (formerly) Antigen Express, Transgene S.A., and Bavarian Nordic.

Advaxis Inc., Bavarian Nordic, BN Immunotherapeutics, Celldex, Immunocellular, Merck/Immune Design, SELLAS Life Sciences Group, Inc.

(formerly) Galena BioPharma, NuGenerex Immuno-Oncology (formerly) Antigen Express and Transgene S.A.

In addition, other adoptive T-cell therapies, monoclonal antibodies and checkpoint inhibitors also provide competition in the oncology space.

In these areas, competitors include Iovance, Immatics, NexImmune, Repertoire Immune Medicines, Tessa Therapeutics, Adaptimmune, Mana Therapeutics, Bluebird Bio, Cellectis, Kuur Therapeutics, Juno Therapeutics/Celgene/Bristol Myers Squibb, Kite Pharma/Gilead, Novartis, Roche Pharmaceuticals, Merck & Co, AstraZeneca plc and Medimmune, LLC.

In these areas, competitors include Adaptimmune, AstraZeneca plc, Bluebird Bio, Cellectis, Immatics, Iovance, Juno Therapeutics/Celgene/Bristol Myers Squibb, Kite Pharma/Gilead, Kuur Therapeutics, Medimmune, LLC, Merck & Co, NexImmune, Novartis, Repertoire Immune Medicines, Roche Pharmaceuticals and Tessa Therapeutics.

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.

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“Immunogenic Antigen Identification from a Pathogen and Correlation to Clinical Efficacy”

"T cell performance assay as a prognostic factor for clinical outcome"

“T cell performance assay as a prognostic factor for clinical outcome”

In partial consideration for the exclusive rights granted under the BCM License Agreement, Marker Cell Therapy, Inc., an entity that is now our wholly owned subsidiary, issued shares of its common stock to BCM valued at approximately $5.0 million at the time of issuance.

Such initial equity issuance was exchanged into merger consideration of 1,490,813 shares of our common stock and warrants to acquire 540,643 shares of our common stock in connection with the merger we completed in October 2018.

Such initial equity issuance was exchanged into merger consideration of 149,081 shares of our common stock and warrants to acquire 54,064 shares of our common stock in connection with the merger we completed in October 2018, each as adjusted to reflect the reverse stock split that we effected in January 2023.

Additional consideration includes a royalty paid on net sales by us to BCM according to the royalty schedule in the BCM License Agreement.

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We are also responsible for sublicensing fees.

In addition, under the BCM License Agreement,

we are responsible for reimbursing BCM for patent-related expenses.

In addition, under the BCM License Agreement, we are responsible for reimbursing BCM for patent-related expenses.

BCM is responsible for filing, prosecuting and maintaining all patent applications and patents included in the licensed patent rights, and we have agreed to reimburse BCM for all such related legal costs incurred after the date of the BCM License Agreement, except such legal costs shall be reduced on a pro-rata basis on a patent or patent application basis should BCM license such patent or patent application in additional fields of use to any third party.

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We have entered into additional agreements with BCM with respect to a strategic alliance to advance pre-clinical 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 product manufacturing and support, including personnel and space at the institution for the foreseeable future.

Mayo Foundation for Medical Education and Research Relationships

We have exclusively licensed the intellectual property for our TPIV100/110 HER2/neu breast cancer vaccine and TPIV200 folate receptor alpha vaccine product candidates from the Mayo Foundation for Medical Education and Research, or the Mayo Foundation.

As part of our business strategy, we establish business relationships, including collaborative arrangements, with other companies and medical research institutions to assist in the clinical development of certain of our drugs and drug candidates and to provide support for our research programs.

Below is a brief description of our significant business relationships and collaborations and related license agreements with Mayo Foundation that expand our pipeline and provide us with certain rights to existing and potential new products and technologies.

Following approval of the IND by the FDA in July 2011, we executed a Sponsored Research Agreement with the Mayo Foundation for the clinical trial.

Mayo Patent & Know-How License

On March 25, 2012, we entered into a Patent & Know-How License Agreement with the Mayo Foundation pursuant to which we licensed certain intellectual property rights from the Mayo Foundation for the development and commercialization of certain products, methods and processes property relating to a proprietary HER2/neu technology.

The Mayo Foundation granted us a license (with a right to sublicense) on a worldwide basis to make, sell and use products for prophylactic and therapeutic use.

This license is an exclusive license for products that are based on the licensed intellectual property and non-exclusive for products that are based on Mayo Foundation know–how and materials.

The intellectual property licensed includes U.S.

patents 9,814,767 (estimated expiration date February 15, 2033) and 10,117,919 (estimated expiration date February 15, 2033) and European patent 2814836 (estimated expiration date February 15, 2033).

Under this agreement, and subject to certain exceptions, we are responsible for, among other things, developing the technology under the Patent Rights to bring Licensed Products (as defined in the agreement) to market and costs of filing, prosecution and maintenance of the Patent Rights.

Mayo Foundation controls the prosecution and maintenance of the Patent Rights in consultation with us.

The Mayo Foundation granted this license in exchange for an upfront payment of $250,000 that we paid in three installments.

In addition to the upfront payment, we are to pay an annual license maintenance fee, milestone fees, royalty fees (which will be subject to a minimum annual royalty fee once royalty fees are due), a percentage of sublicense income (if applicable), and a $2,000,000 diligence fee if we fail to initiate a Phase 2 clinical trial for a Licensed Product prior to the eighth anniversary of the agreement.

We have agreed to indemnify and hold Mayo Foundation harmless from any damages caused as a result of (1) the practice or exercise of any rights and assignments granted pursuant to the agreement by or on behalf of us, any affiliate, or any sub-licensee;

(2) research, development, design, manufacture, distribution, use, sale, importation, exportation or other disposition of Licensed Products;

(3) our, any affiliates, or any sub-licensee’s act or omission;

and (4) third party suits for patent infringement involving a Licensed Product.

The term of this agreement runs from March 25, 2012 until the date of the last to expire of the Valid Claims (as defined in the agreement), provided that Mayo Foundation may terminate the agreement if, among other matters, (1) 45 days after providing us with notice of a material breach of this agreement, we fail to cure such breach, (2) we fail to initiate a Phase 3 clinical trial for a Licensed Product prior to the tenth anniversary of the agreement, and (3) we cease to conduct business in the normal event of operations or become insolvent or bankrupt.

We may voluntarily terminate the agreement at any time upon written notice to Mayo Foundation.

Mayo HER2/neu License

On May 4, 2016, we entered into a License and Assignment Agreement with Mayo Foundation, or the Mayo Foundation HER2/neu License, pursuant to which we licensed certain intellectual property rights from the Mayo Foundation for the development and commercialization of certain products, methods and processes property relating to any cancer indication in which the HER2/neu antigen is overexpressed.

The Mayo Foundation HER2/neu License resulted from our exercise of an option that was issued pursuant to a Technology Option Agreement that we entered into with the Mayo Foundation on May 25, 2010.

The Mayo Foundation granted us a license (with a right to sublicense) on a worldwide basis to make, sell and use products for therapeutic use against breast, ovarian, lung and any other cancers that overexpress HER2/neu antigens.

This license is an exclusive license for products that are based on the licensed intellectual property and non-exclusive for products that are based on Mayo Foundation know–how and materials.

The intellectual property licensed includes European patent 2215111 (estimated expiration date October 30, 2028).

Under the Mayo Foundation HER2/neu License, and subject to certain exceptions, we are responsible for, among other things, developing the technology under the Patent Rights to bring Licensed Products (both as defined in the Mayo Foundation HER2/neu License) to market and costs of filing, prosecution and maintenance of the Patent Rights.

Mayo Foundation has sole control over the protection, defense, enforcement, maintenance abandonment and other handling of the Know-How (as defined in the Mayo Foundation HER2/neu License) and Materials (as defined in the Mayo Foundation HER2/neu License).

The Mayo Foundation granted this license in exchange for an initial payment of $300,000.

The Mayo Foundation assigned to us IND #14749, and we assumed all responsibility and liability for this investigational new drug application.

In addition to the initial payment, we are to pay an annual license maintenance fee, milestone fees, royalty fees (which will be subject to a minimum annual royalty fee once royalty fees are due) and, if applicable, a percentage of sublicense income.

(2) research, development, design, manufacture, distribution, use, sale, importation, exportation or other disposition of Licensed Products;

(3) our or any sub-licensee’s act or omission, including negligence or willful misconduct;

and (4) third party suits for patent infringement involving a Licensed Product.

The term of this agreement runs from May 4, 2016 until the date of our last obligation to make payments under the agreement, provided that Mayo Foundation may terminate the agreement if, among other matters, (1) 30 days after providing us with notice of a material breach of this agreement, we fail to cure such breach, (2) 90 days after providing us with written notice, we fail to meet either of the following diligence events (a) initiate a Phase 2 clinical trial for a Licensed Product prior to the second anniversary of the agreement and, once initiated, keep current on all of our Phase 2 funding obligations and (b) initiate a Phase 2b or 3 clinical trial for a Licensed Product prior to the fifth anniversary of the agreement, (3) we fail to make a sale of a Licensed Product by May 4, 2026, and (4) we cease to conduct business in the normal event of operations or become insolvent or bankrupt.

We may voluntarily terminate the agreement at any time upon written notice to Mayo Foundation.

Mayo Folate Receptor Alpha License

On July 21, 2015, we entered into a License and Assignment Agreement with Mayo Foundation, or the Mayo Foundation FRa License, pursuant to which we licensed certain intellectual property rights from the Mayo Foundation for the development and commercialization of certain products, methods and processes property relating to a Folate Receptor Alpha immunotherapeutic vaccine comprised of a set of unique peptide epitopes targeting breast, lung and ovarian cancer.

The Mayo Foundation FRa License resulted from our exercise of an option that we acquired from Ayer Special Situations Fund I, LP, or Ayer, that was issued pursuant to a Technology Option Agreement that Ayer entered into with the Mayo Foundation on March 19, 2014.

The Mayo Foundation granted us a license (with a right to sublicense) on a worldwide basis to make, sell and use products for therapeutic use against breast, ovarian, lung and other cancers that overexpress Folate Receptor Alpha.

This license is an exclusive license for products that are based on the licensed intellectual property and non-exclusive for products that are based on Mayo Foundation know–how and materials.

The intellectual property that is licensed includes US patents 8,486,412 (estimated expiration date April 3, 2029), 8,858,952 (estimated expiration date March 10, 2031), 9,243,033 (July 10, 2027) and 9,915,646 (estimated expiration date June 1, 2027).

Under the Mayo Foundation FRa License, and subject to certain exceptions, we are responsible for, among other things, developing the technology under the Patent Rights to bring Licensed Products (both as defined in the Mayo Foundation FRa License) to market and costs of filing, prosecution and maintenance of the Patent Rights.

Mayo Foundation has sole control over the protection, defense, enforcement, maintenance abandonment and other handling of the Know-How (as defined in the Mayo Foundation FRa License) and Materials (as defined in the Mayo Foundation FRa License).

The Mayo Foundation granted this license in exchange for an initial upfront payment of $350,000.

The Mayo Foundation assigned to us IND # 14546, and we assumed all responsibility and liability for this investigational new drug application.

In addition to the initial upfront payment, we are to pay additional upfront payments, an annual license maintenance fee, milestone fees, royalty fees (which will be subject to a minimum annual royalty fee once royalty fees are due), and, if applicable, a percentage of sublicense income.

We have agreed to indemnify and hold Mayo Foundation harmless from any damages caused as a result of (1) the practice or exercise of any rights and assignments granted by the Mayo Foundation FRa License by or on behalf of us or any sub-licensee;

(2) research,

development, design, manufacture, distribution, use, sale, importation, exportation or other disposition of Licensed Products;

(3) our or any sub-licensee’s act or omission, including negligence or willful misconduct;

and (4) third party suits for patent infringement involving a Licensed Product.

The term of this agreement runs from July 21, 2015 until the date of our last obligation to make payments under this agreement, provided that the Mayo Foundation may terminate this agreement if, among other matters, (1) 30 days after providing us with notice of a material breach of this agreement, we fail to cure such breach, (2) 90 days after providing us with written notice, we fail to meet either of the following diligence events (a) initiate a Phase 2 clinical trial for a Licensed Product prior to the 2nd anniversary of the Mayo Foundation FRa License and, once initiated, keep current on all of our Phase 2 funding obligations and (b) initiate a Phase 2b or 3 clinical trial for a Licensed Product prior to the 5th anniversary of the Mayo Foundation FRa License, (3) we fail to make a sale of a Licensed Product by July 21, 2025 and (4) we cease to conduct business in the normal event of operations or become insolvent or bankrupt.

We may voluntarily terminate the Mayo Foundation FRa License at any time upon written notice to Mayo Foundation.

Intellectual Property

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and to operate without infringing valid and enforceable patents and other proprietary rights of third parties.

Our ability to stop third parties from making, using, selling, offering to sell, or importing our products may depend on the extent to which we have rights under valid and enforceable patents or trade secrets that cover these activities — for example, the rights obtained under exclusive license arrangements such as those pursuant to our BCM License Agreement and our Mayo Foundation licenses.

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 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.

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.

To achieve this objective, a strategic focus for us has been identifying and licensing key patents and patent applications that serve to enhance our intellectual property and technology position.

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10,030,252 (estimated expiration date March 17, 2035);

9,988,643 (estimated expiration date March 27, 2035);

10,030,252 (estimated expiration date March 17, 2035).

as well as pending U.S.

patent applications.

The effect of the issued United States patents is that they provide us with patent protection for the claims covered by the patents.

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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.

Foreign patent filings related to our PolyStart technology include Australian patent no.

2015231461 and pending applications in the several jurisdictions, including the European Patent Office.

Patent applications related to our PolyStart technology are pending in Brazil and Canada.

Because of differences in patent laws and laws concerning proprietary rights, the extent of protection provided by U.S.

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The FDA and other regulatory authorities at federal, state, and local levels, as well as in foreign countries, extensively regulate, among other things, the research, development, testing, manufacture, quality control, import, export, safety, effectiveness, labeling, packaging, storage, distribution, record keeping, approval, advertising, promotion, marketing, post-approval monitoring, and post-approval reporting of biologics such as those we are developing.

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.

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.

The process required by the FDA before biologic product candidates may be marketed in the United States generally involves the following:

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For example, on July 24, 2020 and September 13, 2020, the Trump Administration announced several executive orders related to prescription drug pricing that seek to implement several of the administration’s proposals.

As a result, the FDA concurrently released a final rule and guidance in September 2020

providing pathways for states to build and submit importation 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

plans for drugs from Canada.

Further, on November 20, 2020, HHS finalized a regulation removing safe harbor protection for price reductions from pharmaceutical manufacturers to plan sponsors under Part D, either directly or through pharmacy benefit managers, unless the price reduction is required by law.

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In connection with the merger, we changed our name from “TapImmune, Inc.” to “Marker Therapeutics, Inc.” and Private Marker changed its name to “Marker Cell Therapy, Inc.” and became our wholly owned subsidiary.

Our principal executive offices are located at 3200 Southwest Freeway, Suite 2500, Houston, Texas 77027, and our telephone number is (713) 400-6400.

Our principal executive offices are located at 4551 Kennedy Commerce Drive, Houston, Texas 77032, and our telephone number is (713) 400-6400.

Our common stock is listed for trading on the Nasdaq Capital Market under the symbol “MRKR”.

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Compared sentence by sentence after normalising whitespace, quotation marks, case and digits, so re-formatting and restated figures do not read as changed language. Wording changes appear as one removal and one addition. The current filing and the prior one are authoritative.

What changed 10-K

Item 1. Business