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Item 1. Business

2022-03-17 compared with 2021-03-09 · 189 added, 112 removed, 683 unchanged (31% 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 developed our lead product candidates from our MultiTAA-specific T cell technology, which is based on the selective expansion of non-engineered, tumor-specific T cells that recognize tumor associated antigens, or TAAs, which are tumor targets, and then kill tumor cells expressing those targets.

These T cells are designed to recognize multiple tumor targets to produce broad spectrum anti-tumor activity.

We are advancing two pipelines of product candidates as part of our MultiTAA-specific T cell program:

the autologous T cells for the treatment of lymphoma, multiple myeloma, or MM, and selected solid tumors and the allogeneic T cells for the treatment of acute myeloid leukemia, or AML, and acute lymphoblastic leukemia, or ALL.

Because we do not genetically engineer the MultiTAA-specific T cell therapies, we believe that our product candidates are easier and less expensive to manufacture, have lower toxicities than current engineered chimeric antigen receptor, or CAR-T, and T cell receptor-based therapies and may provide patients with meaningful clinical benefit.

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.

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

We are advancing three product candidates as part of our MultiTAA-specific T cell program for:

autologous treatment of lymphoma, and selected solid tumors

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

● 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

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.

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.

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 FDA granted orphan drug designation to MT-401 for the treatment of AML after receiving an allogeneic stem cell transplant.

The 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 recent 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 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%].

● 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.

● 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%].

● 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:

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.

Two of the eight patients achieved objective responses with one complete response and one partial response, with six patients continuing with stable disease.

We submitted an investigational new drug, or IND, application to the United States Food and Drug Administration, or the FDA, to initiate 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 the approximate flat dose equivalent of the current maximum tolerated dose from the ongoing Phase 1 trial.

In the adjuvant setting, patients will be randomized to either MultiTAA-specific T cell therapy at approximately 90 days post-transplant versus standard of care observation, while the active disease patients will receive MT-401 following relapse post-transplant as part of a single-arm group.

We expect to complete the safety lead-in portion of the trial in the first half of 2021.

We anticipate that we will initiate the remainder of the Phase 2 trial in the third quarter of 2021 and complete enrollment of 20 patients in that phase of the trial in the fourth quarter of 2021 in order to report results from the active disease arm of the trial in the first quarter of 2022.

We expect to begin manufacturing MT-401 for the Phase 2 trial at our cGMP manufacturing facility in the third quarter of 2021.

We reported interim data for an ongoing Phase 1/2 clinical trial of the MultiTAA-specific T cell therapy for the treatment of pancreatic adenocarcinoma being conducted by BCM.

In this trial, we have observed a clinical benefit correlated with the post-infusion detection of tumor-reactive T cells in patient peripheral blood and within tumor biopsy samples in patients in the tumor-resection arm of the trial.

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.

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:

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.

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.

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

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 provide treatment to patients 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.

MT-601 for the Treatment of Pancreatic Cancer

We reported interim data for an ongoing Phase 1/2 clinical trial (TACTOPS) of the MultiTAA-specific T cell therapy targeting five TAAs for the treatment of pancreatic adenocarcinoma being conducted by BCM.

In this trial, we have observed a clinical benefit with 4 of 13 patients (31%) showing objective responses in front-line unresectable or metastatic pancreatic cancer which correlated with the post-infusion detection of tumor-reactive T cells in patient peripheral blood and within tumor biopsy samples in patients in the tumor-resection arm of the trial.

These T cells exhibited activity against both targeted antigens and non-targeted TAAs, indicating induction of antigen spreading.

To date, we have not observed any cytokine release syndrome or neurotoxicity in this trial.

We recently began developing MultiTAA-specific T cells in pancreatic cancer with product manufactured with two additional antigens when compared to MT-401, to which we refer as MT-601, starting at a similar dose level used in the TACTOPS study.

MT-601 is a MultiTAA-specific T cell product targeting six tumor-associated antigens which 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 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.

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.

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 December 2020, 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.

Our ongoing clinical trials may be also affected by the COVID-19 pandemic.

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.

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

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

Initiation of Phase 2 Clinical Trial of MT-401 (zedenoleucel) for the Treatment of Post-Transplant AML

In January 2021, we announced that the FDA lifted the partial clinical hold on the Phase 2 clinical trial investigating the safety and efficacy of MT-401 for the treatment of patients with AML post-transplant, permitting us to initiate the trial with the safety lead-in portion that is expected to enroll approximately six patients.

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

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 expect to complete the safety lead-in portion of the trial in the first half of 2021, and we continue to work to identify clinical trial sites.

In January 2021, the United States Adopted Names, orUSAN, Council and the World Health Organization International Nonproprietary Name, or WHO INN, Expert Committee adopted “zedenoleucel” as the non-proprietary name for MT-401.

The USAN Council previously accepted “zelenoleucel” as the non-proprietary name for MT-401.

The USAN Council forwarded the name to the WHO INN Expert Committee for additional review and clearance.

The WHO INN Expert Committee revised the name to zedenoleucel to avoid a conflict with the existing INN selenomethothionine (75Se) and could evoke that the substance is selenium-labelled.

The USAN Council agreed with the WHO INN Expert Committee’s revision of the name from “zelenoleucel” to “zedenoleucel.”

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 have 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 expect to complete the safety lead-in portion of our Phase 2 trial in post-transplant AML in the first half of 2021.

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

We expect our current Good Manufacturing Practices, or cGMP, manufacturing facility in Houston, Texas will be fully operational to support our clinical manufacturing in the first half of 2021.

Until that time, we anticipate that clinical product manufacturing will be conducted at BCM’s Good Manufacturing Practices, or GMP, cell manufacturing facility.

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

Our current Good Manufacturing Practices, or cGMP, manufacturing facility in Houston, Texas is fully operational to support our clinical manufacturing.

Before our new facility was operational, clinical product manufacturing was conducted at BCM’s GMP cell manufacturing facility.

· Continue to collaborate with our partners and increase our internal research and development activities to improve and develop adoptive cell therapy technologies.

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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.

We plan 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.

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.

· Invest in our platform to maximize the beneficial outcomes for cancer patients.

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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 mixed with specific antigens.

The cells are retrieved and either genetically modified to express tumor-specific CARs or TCRs or stimulated with specific antigens.

The cells are then cultured to proliferate, and the proliferated cells are infused into the patient.

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As a source of antigen, we use overlapping peptide libraries spanning each of several immunogenic target antigens that are typically associated with certain types of cancer.

These peptides are at least 15 amino acids in length, overlapping by 11 amino acids and span the entire length of each of the target antigens.

These peptides are at least 15 amino acids in length, overlapping by approximately 11 amino acids and span the entire length of each of the target antigens.

This typical footprint of peptides allows us to induce both CD4 + (helper) and CD8 + (cytotoxic) T cells.

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The MultiTAA-Specific T Cell Therapies

In collaboration with BCM, we are advancing two MultiTAA-specific T cell therapies through clinical development:

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.

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We are pursuing post-transplant AML as the lead indication for the MultiTAA-specific T cell program using our allogeneic therapies.

While the blood source and the antigens for stimulation differ between the autologous and allogeneic therapies, the manufacturing process for each product is identical.

● 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.

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.

While the blood source and the antigens for stimulation differ between the autologous, allogeneic and off-the-shelf therapies, the manufacturing process for each product is identical.

Cancers are heterogeneous in their expression of antigens.

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· Low incidence rate of adverse events.

As of December 2020, 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.

In these trials, there has been only one Grade 3 adverse reaction considered possibly related to the therapy.

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.

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 have submitted an IND to the FDA to initiate a Phase 2 clinical trial in post-allogeneic HSCT patients with AML in both the adjuvant and active disease setting, which may become pivotal pending the results of the interim analysis.

The dose administered in this multicenter trial is the current maximum tolerated dose from the Phase 1/2 trial.

In the adjuvant setting, patients will be randomized to either MT-401 at approximately 90 days post-transplant versus standard of care observation, while the active disease patients will receive MT-401 following relapse post-transplant as part of a single-arm group.

We have initiated the Phase 2 trial, beginning with a safety lead-in portion that is expected to enroll approximately six patients.

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

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.

We expect to complete the safety lead-in portion of the trial in the first half of 2021.

The safety lead-in will be followed by the 160-patient portion of the trial at approximately 20 transplant centers.

Group 1 will comprise 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 40 active disease patients in a single arm, with primary endpoints of complete remission and duration of complete remission.

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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Acute Myeloid Leukemia

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

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.

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In this trial, we treated patients in remission and with active disease post-transplant.

As reported in a recent 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 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.

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%].

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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Pancreatic Cancer

We are developing MT-601 for the treatment of advanced unresectable 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.

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In the patients evaluable in Arm C, MultiTAA-specific T cells were measurable in meaningful numbers as detected by correlative analysis of resected tumor, and significant expansion of the infused MultiTAA-specific T cells was observed, along with broad-based epitope spreading, with significant expansion of endogenous T cells specific for other tumor specific antigens.

All eight patients in the adjuvant setting have received at least the pre-surgery dose of MultiTAA-specific T cells.

Only two of the eight treated patients had all of the per-protocol MultiTAA-specific T cell infusions.

One patient has not yet received any post-operative MultiTAA-specific T cells despite remaining in the trial on an observational basis.

Five patients are still in the trial, while three patients had recurrence of disease.

Two patients have not yet undergone surgery.

As illustrated below with respect to the six patients treated in Arm C (excluding the two patients who have not yet undergone surgery), three of the patients in Arm C remain in the trial, while three patients had recurrence of disease:

As illustrated below with respect to the six patients treated in Arm C, three of the patients in Arm C remain in the trial, while three patients had recurrence of disease:

BCM is currently evaluating the MultiTAA-specific T cell therapy in a Phase 1 clinical trial for the treatment of patients with lymphoma.

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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.

Responses in all six patients who entered CR were associated with an expansion of infused T cells, as well as induction of antigen spreading.

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.

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.

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We have not seen a meaningful difference in response rates or durability between the two arms and intend to standardize future trials based upon a protocol wherein patients will receive MultiTAA-specific T cell therapy immediately post-transplant.

As reported in a recent publication by Lulla et al., of the 12 patients that had been treated in the active MM group with a median of 3.5 prior lines:

As reported in a 2021 publication by Lulla et al., of the 12 patients that had been treated in the active MM group with a median of 3.5 prior lines:

● One patient had a CR;

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Instead, the patients are evaluated for any immediate infusion-related reactions and can then usually be discharged within two hours.

Our manufacturing process is illustrated below:

We have established an in-house cGMP manufacturing facility, and we began manufacturing MT-401 for our Phase 2 trial in AML in the fourth quarter of 2021.

Our facility allows for production of MultiTAA-specific T cell products according to FDA guidelines and is designed to be scalable using modular processes.

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:

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

Based on a preliminary analysis of 34 patients enrolled in the triple negative breast cancer trial as of September 30, 2019, 31 patients showed meaningful immune response to vaccine treatment.

These data are subject to final review by independent biostatistical analysis.

As of December 31, 2020, 16 of the patients treated have shown disease progression following treatment with TPIV200.

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

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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.

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.

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Manufacturing

In January 2021, we announced that we had completed the construction and qualification of our cGMP manufacturing facility in Houston, Texas.

Our facility will allow for production of MultiTAA-specific T cell products according to FDA guidelines and is designed to be scalable using modular processes.

We have initiated the technology transfer process and expect the facility to be fully operational in the first half of 2021.

Until that time, we will continue to rely on BCM to manufacture our MultiTAA-specific T cell therapies, as well as the raw materials, our active pharmaceutical ingredients, or APIs, and finished solid dose products for our peptide vaccines for clinical uses, including our Phase 2 trial in AML.

We anticipate using our manufacturing facility to produce commercial supply of any approved product candidates.

We completed the construction and qualification of our cGMP manufacturing facility in Houston, Texas in January 2021, and we began manufacturing MT-401 for our Phase 2 trial in AML in the fourth quarter of 2021.

Our facility allows for production of MultiTAA-specific T cell products according to FDA guidelines and is designed to be scalable using modular processes.

Prior to that time, we relied on BCM to manufacture our MultiTAA-specific T cell therapies, and we continue to rely on BCM to manufacture the raw materials, our active pharmaceutical ingredients, or APIs, and finished solid dose products for our peptide vaccines for clinical uses.

We anticipate using our manufacturing facility to produce clinical supply of MT-601 and commercial supply of any approved product candidates.

Our supply chain for manufacturing raw materials, API, peptide vaccines and MultiTAA-specific T cell therapies ready for distribution and commercialization is a multi-step process.

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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 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;

(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;

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to obtain and maintain licenses to use intellectual property owned by third parties;

and to operate without infringing the 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 — in other words, the rights obtained under exclusive license arrangements such as those pursuant to our BCM License Agreement and our Mayo Foundation licenses.

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.

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

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.

Currently, all of our MultiTAA-specific T cell intellectual property rights are licensed from BCM.

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We reassess the value of each patent at the time maintenance fees are due, and in cases where maintaining the patent is judged to be of no significant strategic value, we decline to pay the maintenance fee.

There can be no assurance that our patents, and any patents that may be issued or licensed to us in the future, will afford protection against competitors with similar technology.

In addition, no assurances can be given that the patents issued or licensed to us will not be infringed upon or designed around by others or that others will not obtain patents that we would need to license or design around.

If the courts uphold existing or future patents containing broad claims over technology used by us, the holders of such patents could require us to obtain licenses to use such technology.

There can be no assurance that our patents, and any patents that may be issued, assigned, or licensed to us in the future, will afford protection against competitors with similar technology.

In addition, no assurances can be given that any patents issued, assigned, or licensed to us will not be infringed upon or designed around by others or that others will not obtain patents that we would need to license or design around.

If existing or future patents held by third parties and containing broad claims over technology used by us were upheld by a court or other authority of competent jurisdiction, the holders of such patents could require us to obtain licenses to use such technology.

Patent coverage may also vary from country to country based on the scope of available patent protection.

There are also opportunities to obtain an extension of patent coverage for a product in certain countries, which adds further complexity to the determination of patent life.

Moreover, in the United States, patent term may be adjusted to account for delays by the United States Patent and Trademark Office, or USPTO, during prosecution.

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.

We currently have a number of issued and pending patents covering composition of matter of our PolyStart technology and methods of using our PolyStart technology, including:

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While the expiration of a product patent normally results in a loss of market exclusivity for the covered product or product candidate, commercial benefits may continue to be derived from , for example:

(1) later- expiring patents on processes and intermediates related to more economical methods of manufacture of the active ingredient of such product;

(1) later- expiring patents on processes and intermediates related to improved methods of manufacture of the active ingredient of such product;

(2) patents relating to the use of such product;

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The coverage claimed in a patent application can be significantly reduced before the patent is issued.

Accordingly, we do not know whether any of the applications we will acquire, or license will result in the issuance of patents, or, if any patents are issued, whether they will provide significant proprietary protection or will be challenged, circumvented or invalidated.

Accordingly, we do not know whether any of the patent applications we own, will acquire, license, or will license will issue as patents, or, if any patents are issued, whether they will provide significant proprietary protection or will be challenged, circumvented or invalidated.

Because unissued U.S.

patent applications are maintained in secrecy for a period of eighteen months and U.S.

patent applications filed prior to November 29, 2000 are not disclosed until such patents are issued, and since publication of discoveries in the scientific or patent literature often lags behind actual discoveries, we cannot be certain of the priority of inventions covered by pending patent applications.

Moreover, we may have to participate in opposition proceedings in a foreign patent office, or for United States patent applications filed before March 16, 2013, in interference proceedings declared by the United States Patent and Trademark Office, or the USPTO, to determine priority of invention, or in United States inter partes review or post-grant review procedures, any of which could result in substantial cost to us, even if the eventual outcome is favorable to us.

There can be no assurance that the patents, if issued, would be held valid by a court of competent jurisdiction.

patent applications filed prior to November 29, 2000 are not disclosed until such patents are issued, and since publication of discoveries/inventions in the scientific or patent literature often lags behind actual discovery/invention, we cannot be certain of the priority of inventions covered by pending patent applications and whether potentially relevant earlier patent filings exist.

Moreover, we may have to participate in opposition proceedings in a foreign patent office, or for United States patent applications filed before March 16, 2013, in interference proceedings declared by the USPTO, to determine priority of invention, or in United States inter partes review or post-grant review procedures, any of which could result in substantial cost to us, even if the eventual outcome is favorable to us.

There can be no assurance that the patents, if issued, would be held valid by a court or other authority of competent jurisdiction.

An adverse outcome could subject us to significant liabilities to third parties, require disputed rights to be licensed from third parties, or require us to cease using such technology.

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.

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

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.

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

patents or proprietary rights owned by us may differ from that of their foreign counterparts.

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federal civil and criminal false claims laws and civil monetary penalty laws, which prohibit, among other things, individuals or entities from knowingly presenting, or causing to be presented, claims for payment to the federal government, including federal healthcare programs, that are false or fraudulent;

HIPAA, which created additional federal criminal statutes which prohibit, among other things, executing a scheme to defraud any healthcare benefit program and making false statements relating to healthcare matters, and which, as amended by HITECH, also imposes certain requirements on HIPAA covered entities and their business associates and covered subcontractors relating to the privacy, security and transmission of individually identifiable health information;

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 annually report to the federal government, information related to payments or other transfers of value made to covered health care professionals and teaching hospitals, as well as ownership and investment interests held by health care professionals and their immediate family members;

the Health Insurance Portability and Accountability Act, or HIPAA, which created additional federal criminal statutes which prohibit, among other things, executing a scheme to defraud any healthcare benefit program and making false statements relating to healthcare matters, and which, as amended by Health Information Technology for Economic and Clinical Health Act, or HITECH, also imposes certain requirements on HIPAA covered entities and their business associates and covered subcontractors relating to the privacy, security and transmission of individually identifiable health information;

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 annually report to the federal government, information related to payments or other transfers of value made to physicians (as defined by the Physician Payments Sunshine Act), other covered physicians and teaching hospitals, as well as ownership and investment interests held by health care professionals and their immediate family members;

state and foreign law equivalents of each of the above federal laws, which, in some cases, differ from each other in significant ways, and may not have the same effect, thus complicating compliance efforts.

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This process will require us to provide scientific and clinical support for the use of our products to each third-party payor separately, with no assurance that coverage and adequate reimbursement will be applied consistently or obtained in the first instance.

Further, coverage policies and third-party reimbursement rates may change at any time.

Even if favorable coverage and reimbursement status is attained for one or more products for which the Company receives regulatory approval, less favorable coverage policies and reimbursement rates may be implemented in the future.

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.

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The ACA contained a number of provisions of particular importance to the pharmaceutical and biotechnology industries, including, but not limited to, those governing enrollment in federal healthcare programs, a new methodology by which rebates owed by manufacturers under the Medicaid Drug Rebate Program are calculated for drugs that are inhaled, infused, instilled, implanted or injected, and annual fees based on pharmaceutical companies’ share of sales to federal health care programs.

There remain judicial and Congressional challenges to certain aspects of the ACA, and we expect there will be additional challenges and amendments to the ACA in the future.

There have been executive, judicial and Congressional challenges to certain aspects of the ACA.

For example, the Tax Cuts and Jobs Act was enacted, which, among other things, removed penalties for not complying with ACA’s individual mandate to carry health insurance.

In addition, the 2020 federal spending package permanently eliminated, effective January 1, 2020, the ACA-mandated “Cadillac” tax on high-cost employer-sponsored health coverage and medical device tax and, effective January 1, 2021, also eliminated the health insurer tax.

On December 14, 2018, a Texas U.S.

District Court Judge ruled that the ACA is unconstitutional in its entirety because the individual mandate was repealed by Congress as part of the Tax Cuts and Jobs Act.

Additionally, on December 18, 2019, the U.S.

Court of Appeals for the 5th Circuit upheld the District Court ruling that the individual mandate was unconstitutional and remanded the case back to the District Court to determine whether the remaining provisions of the ACA are invalid as well.

The United States Supreme Court is currently reviewing this case, although it is unclear when a decision will be made.

Although the Supreme Court has yet ruled on the constitutionality of the ACA, on January 28, 2021, President Biden issued an executive order to initiate a special enrollment period from February 15, 2021 through May 15, 2021 for purposes of obtaining health insurance coverage through the ACA marketplace.

The executive order also instructs certain governmental agencies to review and reconsider their existing policies and rules that limit access to healthcare, including, among others, reexamining Medicaid demonstration projects and waiver programs that include work requirements, and policies that create unnecessary barriers to obtaining access to health insurance coverage through Medicaid or the ACA.

It is also unclear how the Supreme Court ruling, other such litigation, and the healthcare reform measures of the Biden administration will impact the ACA and our business.

Other legislative changes have been proposed and adopted since the ACA was enacted, including aggregate reductions of Medicare payments to providers of 2% per fiscal year through 2030, except for a temporary suspension from May 1, 2020 through March 31, 2021 due to the COVID-19 pandemic, unless additional Congressional action is taken, and reduced payments to several types of Medicare providers.

On June 17, 2021, the U.S.

Supreme Court dismissed a challenge on procedural grounds that argued the ACA is unconstitutional in its entirety because the “individual mandate” was repealed by Congress.

Thus, the ACA will remain in effect in its current form.

Prior to the U.S.

Supreme Court ruling, on January 28, 2021, President Biden issued an executive order that initiated a special enrollment period for purposes of obtaining health insurance coverage through the ACA marketplace.

The executive order also instructed certain governmental agencies to review and reconsider their existing policies and rules that limit access to healthcare, including, among others, reexamining Medicaid demonstration projects and waiver programs that include work requirements, and policies that create unnecessary barriers to obtaining access to health insurance coverage through Medicaid or the ACA.

It is possible that the ACA will be subject to judicial or Congressional challenges in the future.

It is also unclear how such challenges, other such litigation, and the healthcare reform measures of the Biden administration will impact the ACA and our business.

Other legislative changes have been proposed and adopted since the ACA was enacted, including aggregate reductions of Medicare payments to providers of 2%, which due to subsequent legislative amendments, including the Infrastructure Investment and Jobs Act, will stay in effect per fiscal year through 2031, except for a temporary suspension from May 1, 2020 through March 32, 2021 due to COVID-19 relief legislation, unless additional Congressional action is taken, and reduced payments to several types of Medicare providers.

Under current legislation the actual reduction in Medicare payments will vary from 1% in 2022 to up to 3% in the final fiscal year of this sequester.

Additionally, on March 11, 2021, President Biden signed the American Rescue Plan Act of 2021 into law, which eliminates the statutory Medicaid drug rebate cap, currently set at 100% of a drug’s average manufacturer price, for single source and innovator multiple source drugs, beginning January 1, 2024.

Congress is also considering additional health reform measures as part of other reform initiatives.

Moreover, there has recently been heightened governmental scrutiny over the manner in which manufacturers set prices for their marketed products, which has resulted in several Congressional inquiries and proposed and enacted federal and state legislation designed to, among other things, bring more transparency to product pricing, review the relationship between pricing and manufacturer patient programs, and reform government program reimbursement methodologies for drug products.

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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 released a final rule on September 24, 2020, effective November 30, 2020, providing guidance 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.

The implementation of the rule has been delayed by the Biden administration from January 1, 2022 to January 1, 2023 in response to ongoing litigation.

The rule also creates a new safe harbor for price reductions reflected at the point-of-sale, as well as a safe harbor for certain fixed fee arrangements between pharmacy benefit managers and manufacturers, the implementation of which have also been delayed pending review by the Biden administration until March 22, 2021.

On November 20, 2020, CMS issued an interim final rule implementing President Trump’s Most Favored Nation executive order, which would tie Medicare Part B payments for certain physician-administered drugs to the lowest price paid in other economically advanced countries, effective January 1, 2021.

On December 28, 2020, the United States District Court in Northern California issued a nationwide preliminary injunction against implementation of the interim final rule.

However, it is unclear whether the Biden administration will work to reverse these measures or pursue similar policy initiatives.

As a result of litigation challenging the Most Favored Nation model, on December 27, 2021, CMS published a final rule that rescinded the Most Favored Nation model interim final rule.

In July 2021, the Biden administration released an executive order, “Promoting Competition in the American Economy,” with multiple provisions aimed at prescription drugs.

In response to Biden’s executive order, on September 9, 2021, HHS released a Comprehensive Plan for Addressing High Drug Prices that outlines principles for drug pricing reform and sets out a variety of potential legislative policies that Congress could pursue as well as potential administrative actions HHS can take to advance these principles.

No legislation or administrative actions have been finalized to implement these principles.

However, it is unclear whether these or similar policy initiatives will be implemented in the future.

At the state level, legislatures have increasingly passed legislation and implemented regulations designed to control pharmaceutical product pricing, including price or patient reimbursement constraints, discounts, restrictions on certain product access and marketing cost disclosure and transparency measures, and, in some cases, designed to encourage importation from other countries and bulk purchasing.

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Corporate Information

We were incorporated under the laws of the State of Nevada in 1991 under the name "TapImmune, Inc."

and reincorporated in Delaware in October 2018 under the name "Marker Therapeutics, Inc."

On October 17, 2018, we completed a business combination with a Delaware corporation that was then known as "Marker Therapeutics, Inc.,"

or Private Marker, in accordance with the terms of the Agreement and Plan of Merger and Reorganization dated as of May 15, 2018, or the Merger Agreement, by and among us, Private Marker and Timberwolf Merger Sub, Inc., a Delaware corporation and a wholly owned subsidiary of TapImmune, or Merger Sub, pursuant to which, among other matters, Merger Sub merged with and into Private Marker, with Private Marker continuing as a wholly owned subsidiary of TapImmune and the surviving corporation of the merger.

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.

We were incorporated under the laws of the State of Nevada in 1991 under the name “TapImmune, Inc.” and reincorporated in Delaware in October 2018 under the name “Marker Therapeutics, Inc.” On October 17, 2018, we completed a business combination with a Delaware corporation that was then known as “Marker Therapeutics, Inc.,” or Private Marker, in accordance with the terms of the Agreement and Plan of Merger and Reorganization dated as of May 15, 2018, or the Merger Agreement, by and among us, Private Marker and Timberwolf Merger Sub, Inc., a Delaware corporation and a wholly owned subsidiary of TapImmune, or Merger Sub, pursuant to which, among other matters, Merger Sub merged with and into Private Marker, with Private Marker continuing as a wholly owned subsidiary of TapImmune and the surviving corporation of the merger.

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 common stock is listed for trading on the Nasdaq Capital Market under the symbol "MRKR".

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

Available Information

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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