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Item 1. Business

2024-03-26 compared with 2023-03-22 · 146 added, 231 removed, 487 unchanged (44% of the section changed)

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 and potentially recruit the patient’s immune system to participate in the cancer killing process.

We developed our lead product candidates from our multi tumor associated antigen (“multiTAA”)-specific T cell technology, which is based on the manufacture of non-engineered, tumor-specific T cells that recognize multiple tumor-associated antigens, or TAAs.

This approach selectively expands tumor-specific T cells from a patient’s/donor’s blood and is able to recognize multiple tumor targets to produce broad spectrum anti-tumor activity.

Targeting multiple antigens simultaneously exploits the natural capacity of T cells to recognize and kill tumor targets via native T cell receptors (“TCR”), while limiting tumor adaptation/escape by antigen-negative selection or antigen down-regulation.

When infused into a patient with cancer, the multiTAA-specific T cells are designed to kill cancer cells expressing the TAA and potentially recruit the patient’s immune system to participate in the cancer killing process.

We licensed the underlying technology for multiTAA-specific T cell therapy from Baylor College of Medicine, or BCM, in March 2018.

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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.

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 AML

off-the-shelf products in various indications

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

We are advancing two product candidates for 3 clinical indications as part of our multiTAA-specific T cell program for:

● Autologous multiTAA product for the treatment of lymphoma and pancreatic cancer (MT-601)

● Off-the-Shelf (OTS) product in various indications (e.g., MT-401-OTS)

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

● Multiple targets → enhanced tumoricidal effect→ minimized tumor immune escape

● 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.

● Clinical safety → no treatment-related side effects, including cytokine release syndrome (CRS) or other severe adverse effects (SAEs), were attributed to the use of multiTAA-specific T cell therapies to date

● Non-genetically engineered T cell products → selective expansion of tumor-specific T cells from a patient’s or donor’s blood capable of recognizing a broad range of tumor antigens → no risk of mutagenesis and reduced manufacturing complexity → lower cost

For these reasons, we believe our endogenous T cell receptor-based therapies may provide meaningful clinical benefit and safety to patients with both hematological and solid tumors.

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.

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 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.

For example, we are assessing the potential of combining multiTAA-specific T cell products with other products.

Company-Sponsored Clinical Development of MultiTAA Specific T Cell Therapies

MT-601 for the Treatment of Lymphoma

We developed MT-601, a multiTAA-specific autologous T cell product capable of recognizing multiple target antigens expressed by the tumor, thereby limiting tumor adaptation by negative antigen selection or downregulation.

We are evaluating the safety and efficacy of MT-601 in a Phase 1, multicenter, open-label study (APOLLO) in participants with relapsed or refractory lymphoma who either failed or are ineligible for anti-CD19 CAR T cell therapy.

MT - 601 is a multiTAA-specific T cell product that specifically targets six different tumor antigens upregulated in lymphoma cells (Survivin, PRAME, WT1, NY-ESO-1, SSX-2, MAGEA-4).

In August 2022, the FDA cleared our IND application for MT-601 for the treatment of patients with relapsed/refractory non-Hodgkin lymphoma who have failed or are ineligible to receive anti-CD19 CAR T cell treatment.

The Phase 1 APOLLO trial was initiated in January 2023.

In June 2023, we reported first enrollment in the dose escalation stage of the Phase 1 study.

The study participant tolerated the treatment well without treatment-related adverse events and achieved a complete metabolic response eight weeks after the second infusion of MT - 601.

Six months following the initial treatment with MT-601 the study participant has maintained a complete response to treatment and will continue to be monitored for long-term treatment effects and durability of response.

To further validate these observations, additional patients are currently being enrolled in the Phase 1 study.

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.

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

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

The FDA cleared our IND application for MT-601 in November 2022 to initiate the PANACEA study, a Phase 1 multicenter clinical trial in locally advanced, unresectable or metastatic pancreatic cancer to assess the safety and efficacy of MT-601 in combination with front-line chemotherapy.

The PANACEA trial will include a dose escalation portion followed by a dose expansion portion.

Clinical advancement will be pending additional financial support from non-dilutive grant activities.

MT-401 for the Treatment of Patients with AML and MT-401-OTS Program

MT-401 ARTEMIS Study:

We previously announced discontinuation of the Phase 2 ARTEMIS study to prioritize the MT-401-OTS program in patients with Acute Myeloid Leukemia (AML) and Myelodysplastic Syndromes (MDS).

The previous ARTEMIS study was investigating MT-401 (zedenoleucel), in post-allogeneic hematopoietic stem cell transplant (HSCT) patients with AML.

The study had three treatment arms, including patients with measurable residual disease (MRD), as well as patients with MRD negative complete remission or active disease.

The dose administered in this multicenter trial was up to 200 million cells every two weeks for up to three doses.

● In April 2020, the Orphan Product Development Office of the United States Food and Drug Administration, or the FDA, granted orphan drug designation to MT-401 (zedenoleucel), a multiTAA-specific T cell therapy that targets four TAAs, for the treatment of AML.

● The same multiTAA-specific T cell therapy has been well tolerated in an ongoing Phase 1 clinical trial in AML and myelodysplastic syndrome, or MDS, conducted by our strategic partner Baylor College of Medicine, or BCM.

● 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 HSCT were relapse free [median leukemia-free survival, or LFS, not reached at a median follow-up of 1.9 years], with 11 of 15 patients (two patients were each treated during two different remissions) remaining alive (estimated two-year overall survival of 77%) at a median follow-up of 1.9 years post-infusion, which compares favorably with HSCT outcomes for risk-matched AML/MDS patients post-HSCT [median LFS of nine to 15 months and two-year survival probability of 42%].

● Additionally, eight patients were treated for active disease that was resistant to salvage therapy post-HSCT with a median of five prior lines of therapy (range:

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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.

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:

In 2021, the ARTEMIS trial conducted by Marker has completed the safety lead-in portion, which tested the comparability of MT-401 or zedenoleucel, the multiTAA-specific T cell product manufactured using peptides from two different vendors and enrolled six patients with active disease:

one measurable residual disease (MRD) positive patient and five frank relapse patients.

● Consistent with the results of the BCM Phase 1 trial, there were no dose-limiting toxicities, cytokine release syndrome or neurotoxicity observed in this stage of the trial, 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.

● 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\.

Correlative studies showed that the patient saw significant expansion of infused multiTAA-specific T cells.

There were no objective responses from the frank relapse patients.

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● 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.

We transitioned to treating patients using MT-401 manufactured with Marker’s new T cell manufacturing process.

The improved manufacturing process greatly reduced the manufacturing time and increased both the antigen specificity and diversity.

Specifically, the new process involves an improved T cell manufacturing process for MT-401 that reduces production time to 9 days (compared to the original process of >30 days).

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.

This allows a 90% decrease in the number of interventions during production and an improved final T cell product compared to the original product used in previous clinical trials on multiTAA-specific T cells.

● After completing the safety lead-in portion, we initiated the remainder of the Phase 2 trial in July 2021.

Group 1 comprised adjuvant (disease-free) patients, with the primary endpoint of relapse-free survival of patients randomized to receive MT-401 versus a control group.

Group 2 comprised active disease patients in 2 single arm cohorts (MRD+ only and active disease), with primary endpoints of complete remission and duration of complete remission.

We were previously awarded grants from the FDA Orphan Products Grant program ($2 million), NIH Small Business Innovation Research (SBIR) program ($2 million) and the Cancer Prevention and Research Institute of Texas (CPRIT, $13 million), to support the Phase 2 clinical trial of MT-401.

All funding agencies have agreed to continue their financial support and to shift funds to the MT-401-OTS program.

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 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.

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

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.

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.

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, 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.

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

Marker previously announced that it intends to focus on the advancement of the MT-401-OTS program in patients with AML.

MT - 401-OTS has the potential to provide treatment to patients in as little as 72 hours.

Marker believes that this fast turnaround time would be beneficial for treating patients with rapid cancer progression, such as patients with measurable residual disease (MRD) in the AML setting.

In the OTS program, we intend to dose patients using “banked” products based on partially human leukocyte antigen (HLA) matching.

FDA has cleared our clinical protocol to investigate MT-401-OTS as a treatment in patients with AML.

already established a cellular inventory manufactured from healthy donors, with ongoing efforts to further expand the inventory.

At full scale production, we estimate a single donor could provide treatment for approximately 40 patients, and the current stability program indicates that OTS multiTAA-specific T cell products are stable for more than a year in liquid nitrogen, which we expect will permit future on-demand availability for broad-scale implementation.

We expect to dose the first patient in the second half of 2024, and, if our OTS program shows promising results in the clinic, we intend to expand the OTS platform to other hematological malignancies and solid tumors.

Our clinical-stage pipeline is set forth below:

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:

· Expedite clinical development, regulatory approval, and commercialization of our lead product candidates.

Based on the results of the Phase 1 clinical trials of the multiTAA-specific T cell therapies conducted at BCM, we plan to advance our lead product candidates into Phase 2 clinical trials and facilitate the initiation of company-sponsored clinical trials.

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 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.

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.

We are party to a strategic alliance with BCM, pursuant to which we will sponsor selected research at BCM in support of our technology.

In conjunction with this strategic alliance, BCM will conduct selected Phase 1 and Phase 2 clinical trials of our product candidates.

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 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 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.

Based on the results of the Phase 1 clinical trials of the multiTAA-specific T cell therapies conducted at BCM and the positive clinical data from the Phase 1 APOLLO study, we plan to prioritize the advancement of MT-601 in patients with lymphoma and to advance the MT-401-OTS program in patients with AML.

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

On June 26, 2023, we completed the previously announced transaction with Cell Ready, LLC, or Cell Ready, pursuant to a Purchase Agreement, or the Cell Ready Purchase Agreement, dated May 1, 2023, by and between us and Cell Ready.

Following the Closing Date, on February 22, 2024, we and Cell Ready entered into a long-term contract, pursuant to which Cell Ready will perform a wide variety of services for us, including research and development, and manufacturing in support of our clinical trials.

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

We are contracting with Cell Ready to perform a wide variety of services to ensure the continuation of our research and development efforts and process development to optimize our manufacturing process, product quality and commercial scalability.

We previously optimized the multiTAA-specific T cell manufacturing process by closing the system and reducing the total manufacturing time from the original 36 days (BCM) to nine days.

The improved manufacturing process has been implemented to supply all of the clinical products used in our current company-sponsored clinical trials.

We believe the improved manufacturing process enables products with increased antigen specificity and diversity, both of which have a strong linear correlation to anti-tumor activity and has resulted in a four-fold increase in potency in vitro.

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

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The field of adoptive cell transfer is currently comprised primarily of CAR and TCR engineered T cells and has emerged from principles of basic immunology to become a paradigm-shifting clinical immunotherapy.

T cell therapy has evolved as one of the most promising branches of immunotherapy.

T cell therapy, we believe has evolved as one of the most promising branches of immunotherapy.

T cell immunotherapy involves the infusion of T cells into a patient.

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Once infused, the natural characteristics of T cells take over and the T cells multiply in quantity, forming an army of T cells that kill the targeted cancer cells.

We have observed evidence of “epitope spreading” in our clinical trials, suggesting that the multiTAA-specific T cell therapy is inducing an enhanced response by the patient’s own T cells (specific for an expanded set of tumor-associated antigens beyond those targeted by the infused product).

Correlative analyses show expansion of endogenous T cells, other than those present in the infused product, in the months following infusion.

This phenomenon, also known as “antigen spreading,” is potentially important in generating a deep and durable response for a patient because it enables the killing of tumors that do not express any of the antigens initially targeted by our therapy and could be due to the lack of lymphodepletion that allows recruitment of the endogenous immune system for anti-tumor activity.

The MultiTAA-Specific T Cell Therapies

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

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

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.

The stem cell transplant donor is used as the source of the cells manufactured for our allogeneic therapies.

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

● Off-the-shelf multiTAA-specific T cell therapies - We plan to enroll patients that will be matched to the pre-manufactured inventory of MT-401-OTS products based on their human leukocyte antigen, or HLA.

We are advancing two multiTAA-specific T cell therapies through clinical development:

Autologous multiTAA-specific T cell therapies – The autologous product targets the NY-ESO-1, PRAME, MAGE - A4, Survivin, WT1 and SSX2 antigens (MT-601).

We recently reported updated clinical data from our Phase 1 clinical trial investigating MT-601 for the treatment of patients with lymphoma who have relapsed after CAR T therapy.

In addition, we received an Investigational New Drug (IND) cleared by the U.S.

FDA to investigate MT-601 in a Phase 1 trial in patients with pancreatic cancer in combination with first-line chemotherapy.

Off-the-Shelf (OTS) multiTAA-specific T cell therapies – The OTS product targets WT1, NY-ESO-1, PRAME, and Survivin antigens (MT-401-OTS).

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.

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

Cancers are heterogeneous in their expression of antigens.

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Therapies targeting only a single antigen are vulnerable to evolutionary escape mechanisms.

While single-antigen specific therapy can eliminate all the tumor cells expressing the targeted antigen, the residual tumor cells that do not express that antigen may survive and expand.

While single-antigen specific therapies can eliminate all the tumor cells expressing the targeted antigen, the residual tumor cells that do not express that antigen may survive and expand.

In addition, tumor cells may also downregulate or mutate the targeted antigen, thus becoming invisible to the T cell therapy.

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This process is referred to as antigen-negative tumor escape.

Our solution to the problem of tumor heterogeneity is the development of T cell products that simultaneously attack multiple tumor-expressed antigens and thereby enable more complete initial tumor targeting, thus minimizing the subsequent opportunity for the cancer to engage escape mechanisms.

Of note, data suggest that this strategy may be responsible for recruitment and activation of unique cancer-killing cells from the patient’s own immune repertoire to participate in cancer eradication, further minimizing the possibility for tumor cell escape.

Our solution to the problem of tumor heterogeneity is the development of T cell products that are intended to simultaneously attack multiple tumor-expressed antigens and thereby enable more complete initial tumor targeting, thus minimizing the subsequent opportunity for the cancer to engage escape mechanisms.

We believe our proprietary multiTAA-specific T cell platform may have meaningful advantages over current CAR and TCR-engineered cell therapy approaches.

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For example, in BCM’s Phase 1 clinical trial in lymphoma, there were complete responses, or CRs, in six of the fifteen evaluable patients with active disease.

Significantly, no patient with a CR has subsequently relapsed with disease, whereas typically 30% or more of patients with CR in reported CAR-T studies relapse within one year.

For example, in BCM’s Phase 1 clinical trial in lymphoma, there were complete responses, or CRs, in six of the fifteen evaluable patients with both Hodgkin lymphoma and non-Hodgkin lymphoma with active disease.

Significantly, no patient with a CR has subsequently

relapsed with disease, whereas typically 30% or more of patients with CR in reported CAR-T studies relapse within one year.

In patient results to date in this trial, observed therapeutic responses appear to be highly durable, with some patients being relapse-free beyond five years.

· Non-gene modified.

In 2023, Marker treated the first patient in the Phase 1 APOLLO trial investigating the safety and efficacy of MT-601 in patients with lymphoma.

Marker recently reported that the first patient treated in this Phase 1 study achieved a complete response 8 weeks after the second dose of MT-601 and that the patient maintained complete response to treatment 6 months after initial infusion with MT - 601.

· Non-genetically modified T cells.

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.

· No need for lymphodepletion before infusion.

Unlike CAR-T therapies, which require lymphodepletion of a patient’s existing T cells so that they will not compete with the infused therapy, the multiTAA-specific T cell therapies work with the natural capabilities of T cells to target cancer and do not require lymphodepletion prior to infusion.

We believe our multiTAA-specific T cell therapy represent a safe alternative to CAR-T cells and can be manufactured at a fraction of the cost of a gene-modified T cell product, with substantially reduced complexity of manufacturing.

· Low incidence rate of adverse events.

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.

· Appears to drive endogenous immune responses.

In our clinical trials, we have observed evidence of “epitope spreading” in the treated patients, meaning that the multiTAA-specific T cell therapy is potentially inducing an enhanced response by the patient’s own T cells (specific for an expanded set of tumor-associated antigens beyond those targeted by the infused product).

Correlative analyses show expansion of endogenous T cells, other than those present in the infused product, in the months following infusion.

This phenomenon, also known as “antigen spreading,” is potentially important in generating a deep and durable response for a patient, because it enables the killing of tumors that do not express any of the antigens initially targeted by our therapy and could be due to the lack of lymphodepletion that allows recruitment of the endogenous immune system for anti-tumor activity.

As of January 2024, the multiTAA-specific T cell therapy was generally well tolerated by the patients across clinical trials in hematological and solid tumor indications, and no treatment-related adverse events, including CRS or neurotoxicity, were attributed to the use of multiTAA-specific T cell therapies to date.

This appears to compare favorably with published CD19 CAR-T studies that have been associated with substantial tolerability concerns, including a Phase 1 trial in which 95% of patients had Grade 3 or higher adverse events during treatment and current investigations by the FDA regarding the risk of CAR-T cell therapies to potentially induce secondary cancers.

· Capable of addressing a broad repertoire of cancer cells.

While CAR-T and TCR therapies generally target a single epitope, our manufacturing process selects for T cells that are specific for multiple peptides derived from several targeted antigens.

Deep gene sequencing of our products shows that a typical patient dose usually consists of approximately 4,000 unique T cell clonotypes, some of which target up to five different tumor-associated antigens.

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.

Deep gene sequencing of our products shows that a typical patient dose usually consists of approximately 4,000 unique T cell clonotypes, some of which target up to six different tumor-associated antigens.

The six antigen targets can be recognized by a very wide range of T cells, which we believe facilitates robust killing of targeted cancer cells.

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

The following clinical trials are being conducted by BCM pursuant to our strategic alliance.

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 each trial, correlative studies showed significant expansion of multiTAA-specific T cells, as well as significant evidence of epitope spreading with expansion of endogenous T cells specific for tumor-associated antigens that were not targeted by the multiTAA-specific T cell therapy.

The following clinical trials were conducted by BCM pursuant to our strategic alliance.

In each trial, correlative studies showed significant expansion of multiTAA-specific T cells, as well as evidence of epitope spreading against tumor-associated antigens that were not targeted by the multiTAA-specific T cell therapy.

Acute Myeloid Leukemia

We are pursuing the development of MT-401 for the treatment of post-transplant AML as the lead indication for the multiTAA-specific T cell program.

Currently, available treatments for post-transplant AML patients are limited and include donor lymphocyte infusion, which has an approximately 15% overall response rate but a 30% to 50% risk of severe and debilitating graft-versus-host disease.

To date, available treatments for post-transplant AML patients are limited and include donor lymphocyte infusion, which has an approximately 15% overall response rate but a 30% to 50% risk of severe and debilitating graft-versus-host disease.

The five-year mortality rate for patients who receive an allogeneic HSCT exceeds 50%, and patients who relapse after a transplant have a survival expectation of approximately 4.5 months.

BCM recently completed a Phase 1 AML/MDS clinical trial of the multiTAA-specific T cell therapy for the treatment of patients with post-transplant AML.

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

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%].

In this trial, patients in remission with high risk for relapse, as well as patients with active disease post-transplant were treated.

As reported in a 2021 publication by Lulla et al., 11 of the 17 patients in the adjuvant disease setting dosed with the multiTAA-specific T cell therapy after receiving an allogeneic HSCT did not relapse during the follow-up period of the study [median LFS not reached at a median follow-up of 1.9 years], with 11 of 15 patients (two patients were each treated during two different remissions) remaining alive (estimated two-year overall survival of 77%) at a median follow-up of 1.9 years post-infusion which compares favorably with HSCT outcomes for risk-matched AML/MDS patients post-HSCT [median LFS of nine to 15 months and two-year survival probability of 42%].

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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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.

As shown below, two of the eight patients achieved objective responses with one complete response and one partial response, with six patients continuing with stable disease.

In this trial, the multiTAA-specific T cell therapy was well tolerated, with no drug-related serious adverse events and no instances of greater than Grade 2 graft-versus-host disease.

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

In this trial, the multiTAA-specific T cell therapy was well tolerated, with no drug-related serious adverse events and no instances of greater than Grade 2 acute graft-versus-host disease or moderate-severe chronic GVHD.

The maximum grade treatment-related adverse event was seen in one patient in the adjuvant disease group who had a possibly drug-related Grade 3 elevation of liver enzymes but was treated with prednisone with complete resolution.

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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.

In this trial, BCM plans to enroll approximately 45 patients with advanced or borderline resectable pancreatic adenocarcinoma in three arms:

Arm A, which includes patients with unresectable/metastatic disease who are responding to standard first-line chemotherapy;

Arm B, which includes patients with progressive disease or therapy intolerance;

and Arm C, which includes patients with surgically resectable disease.

A total of 31 patients were administered the multiTAA-specific T cell therapy:

13 patients in Arm A, 10 patients in Arm B and eight patients in Arm C.

In 2020, we reported that in this trial, BCM administered multiTAA-specific T cells to a total of 31 patients with advanced or borderline resectable pancreatic adenocarcinoma in three arms:

13 patients in Arm A, which included patients with unresectable/metastatic disease who were responding to standard first-line chemotherapy;

12 patients in Arm B, which included patients with progressive disease or therapy intolerance;

and eight patients in Arm C, which includes patients with surgically resectable disease.

Overall, we have observed a clinical benefit correlated with the detection of tumor-reactive T cells in patient peripheral blood (Arms A, B and C) and within tumor biopsy samples (Arm C) post-infusion.

T cells exhibited activity against both targeted antigens as well as non-targeted TAAs, including MAGE-A2B and AFP, indicating induction of antigen/epitope spreading.

No cytokine release syndrome or neurotoxicity has been observed in any arm of the trial to date.

Arm A is designed to evaluate the safety and potential efficacy of using multiTAA-specific T cell therapy as part of first-line treatment for patients with pancreatic cancer.

These patients in the chemo-responsive arm have completed or will complete at least three months of standard-of-care chemotherapy (gemcitabine/nab-paclitaxel or FOLFIRINOX), which is the period during which a response to chemotherapy would typically occur, before receiving up to six administrations of multiTAA-specific T cell therapy in conjunction with chemotherapy.

For 12 of the 13 patients, sufficient cells for all six planned doses were generated;

two doses were available for the remaining patient.

Arm A was designed to evaluate the safety and potential efficacy of using multiTAA-specific T cell therapy as part of first-line treatment for patients with pancreatic cancer.

These patients in the chemo-responsive arm have completed at least three months of standard-of-care chemotherapy (gemcitabine/nab-paclitaxel or FOLFIRINOX), which is the period during which a response to chemotherapy would typically occur, before receiving up to six administrations of multiTAA-specific T cell therapy in conjunction with chemotherapy.

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

o four patients experienced objective responses after administration of multiTAA cells;

o four patients experienced objective responses after administration of multiTAA-specific T cells;

o one patient experienced a radiographic complete response occurring at month nine after starting chemotherapy;

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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);

o one patient experienced a mixed response.

● Patients had durable cancer control with nine of the 13 patients exceeding historical control of overall survival;

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

● Evidence of epitope-spreading was observed in all responders, suggesting that the multiTAA T cell therapy triggered the recruitment of a broader endogenous immune system response for improved anti-tumor activity;

● Evidence of epitope-spreading was observed in all responders, suggesting that the multiTAA-specific T cell therapy triggered the recruitment of a broader endogenous immune system response for improved anti-tumor activity;

● No infusion-related reactions, cytokine release syndrome or neurotoxicity was observed;

● In patients responding to therapy, significant expansion of the infused multiTAA-specific T cell therapy was observed, along with broad-based epitope spreading, with significant expansion of endogenous T cells specific for other tumor specific antigens.

In patients responding to therapy, significant expansion of the infused multiTAA-specific T cell therapy was observed, along with broad-based epitope spreading, with significant expansion of endogenous T cells specific for other tumor specific antigens.

Arm B is designed to evaluate the use of multiTAA-specific T cell therapy as a second-line therapy for patients who have failed first-line chemotherapy.

The patients in this chemo-refractory arm are either ineligible for chemotherapy or have progressed on chemotherapy and have received or are receiving up to six doses of multiTAA-specific T cell therapy as a monotherapy.

The following graphic depicts the best clinical assessment of the 10 evaluable patients in Arm B:

Among the patients who saw clinical disease stabilization, significant expansion of the infused multiTAA-specific T cell therapy was observed, along with broad-based epitope spreading, with significant expansion of endogenous T cells specific for other tumor-specific antigens.

Arm C is designed to assess T cell infiltration and expansion.

These patients with borderline surgically resectable disease received or will receive a dose of multiTAA-specific T cell therapy following chemotherapy, radiotherapy or combination and prior to surgical resection and up to five additional doses of T cells after surgery.

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.

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.

In patients responding to therapy, significant expansion of the infused multiTAA-specific T cell therapy was observed.

BCM evaluated the multiTAA-specific T cell therapy (5 TAA product) in a Phase 1 clinical trial for the treatment of patients with lymphoma.

A total of 32 patients received two protocol-specified infusions of multiTAA-specific T cells, 14 with Hodgkin lymphoma, or HL, and 18 with aggressive non-Hodgkin lymphoma, or NHL, [diffuse large B-cell lymphoma, or DLBCL, (n=12), mantle cell lymphoma, or MCL, (n=2), T-cell lymphoma (n=3) and composite lymphoma (HL and DLBCL, n=1)].

As reported in a recent publication by Vasileiou et al., BCM had treated 15 patients with active disease, which we refer to as the active lymphoma group, all of whom had completed a follow-up period beyond three months post-infusion.

These patients were heavily pre-treated and, on average, had failed a median of five prior lines of therapy (range four to eight) for the HL patients and a median of three prior lines of therapy (range three to four) for the NHL patients.

As reported in a recent publication by Vasileiou et al., BCM had treated 15 patients with active disease (active lymphoma group), all of whom had completed a follow-up period beyond three months post-infusion.

These patients were heavily pre-treated and had failed a median of five prior lines of therapy (range four to eight) for the HL patients and a median of three prior lines of therapy (range three to four) for the NHL patients.

As illustrated below, in the active lymphoma group, six patients entered CR and nine patients had experienced stable disease.

None of the patients in CR had relapsed, and the range for the duration of CR in these patients were between two and over five years after being infused with the multiTAA-specific T cell therapy with the exception of one CR patient who died of an unrelated pneumonia.

None of the patients in CR had relapsed, and the range for the duration of CR in these patients was between two and over five years after being infused with the multiTAA-specific T cell therapy with the exception of one patient who died of an unrelated pneumonia while in a CR.

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.

BCM also treated 17 patients, including one patient who was treated a second time after a relapse, in remission (adjuvant lymphoma group).

Like the active lymphoma group, these patients were heavily pre-treated with seven patients with HL treated with a median of 4 prior lines of therapy (range three to five) and 10 patients with NHL with a median of three prior lines of therapy (range one to five).

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The duration of response ranged from approximately nine months to over five years.

In both treatment groups, the multiTAA-specific T cell therapy was well tolerated, with no drug-related serious adverse events, suggesting that the multiTAA-specific T cell therapy might serve as a standard-of-care maintenance therapy for lymphoma patients in remission.

Further, data from this trial show “epitope spreading,” or expansion of patients’ endogenous T cells (specific for an expanded set of tumor-associated antigens beyond those targeted by the infused therapy) in the months following infusion.

Significantly, we have observed this effect even though some patients in this trial received doses that had not yet been antigen-escalated to the full antigen dose.

Acute Lymphoblastic Leukemia

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

Leukemic relapse is one of the primary causes of treatment failure in HSCT recipients.

Like post-transplant AML patients, post-transplant ALL patients have limited treatment options, with donor lymphocyte infusions similarly associated with the risk of life-threatening graft-versus-host disease.

While CAR-T therapies have shown potent anti-leukemia activity in post-transplant ALL patients, CD19-CAR-T cell therapies target a single antigen, carrying the inherent risk of immune escape, and are most effective in malignancies of B-cell lineage.

In contrast, the multiTAA-specific T cell therapy targets multiple antigens expressed in both B- and T-cell ALL.

In this trial, as reported in February 2019 we had treated 18 patients.

Of the seven evaluable patients:

● All evaluable patients were up to 28 months in CCR;

● One patient experienced relapse displayed mixed donor/recipient chimerism after transplant, but remained in CCR for 6 months;

● Patients who remained in CCR had been durable for between four to 28 months, with a median of 16 months.

Multiple Myeloma

BCM is currently evaluating the multiTAA-specific T cell therapy in a Phase 1b/2a clinical trial for the treatment of patients with MM.

In this trial, we are treating both active and adjuvant post-autologous stem cell transplant MM patients both within 90 days and more than 90 days post-transplant.

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 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;

● Two patients achieved partial responses;

● Nine patients had stable disease following initial multiTAA-specific T cell infusion.

Of the nine patients that had been treated in the adjuvant MM group, all nine patients had remained in CCR, with a median follow-up of 21 months.

Only two patients had relapsed at months seven and 13 after infusion while the remaining patients remain in CCR at a median follow-up of 27.5 months.

In both treatment groups, the multiTAA-specific T cell therapy was well tolerated, with no drug-related serious adverse events.

Process Development and Manufacturing of the MultiTAA-Specific T Cell Therapies

In the manufacturing process, blood is drawn from either the individual patient (in the case of the autologous T cells) or from the allogeneic stem cell transplant donor (in the case of the allogeneic T cells).

In the manufacturing process, blood is drawn from either the individual patient (in the case of the autologous T cells) or from a healthy donors/commercially available leukapheresis material (in the case of the OTS program).

Although the T cells that are selected and expanded by our process exist in a patient’s circulating blood, these T cells are often present at very low frequencies.

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These cells are placed inside a G-Rex manufacturing device and combined with an experimentally optimized mix of GMP-grade cytokines that is used to restore and enhance the functional capability of the cultured T cells.

In addition, libraries of overlapping peptides, which we refer to as peptide pools, spanning the target antigens are combined with antigen presenting cells and added to the cell culture.

In addition, libraries of overlapping peptides, which we refer to as peptide pools, are added to the cell culture.

Each peptide within a peptide pool represents a small segment of a target antigen, which a T cell might recognize.

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Cells manufactured in the device grow efficiently without need for agitation by a technician, scientist or automated system.

Inside the G-Rex, PBMCs are co-cultured with antigen-presenting cells that have been exposed to the stimulating peptide pools.

Inside the G-Rex, PBMCs, including T cells and antigen-presenting cells, are exposed to the stimulating peptide pools.

This results in the selective expansion of T cells that specifically recognize the target antigens.

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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 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.

As a result, our therapy requires only a very small infusion volume that can be administered to patients within minutes at an outpatient center.

Due to the low incidence of adverse events with our therapies, patients do not need to be hospitalized and monitored overnight.

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

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.

The standard dose for patients with lymphoma ranges from 100 to 400 million cells per adult patient.

Manufacturing

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.

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

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.

We face significant competition from organizations, particularly fully integrated pharmaceutical companies that are pursuing pharmaceuticals which are competitive with our drug candidates.

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., 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 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.

The manufacturing process was originally developed at Baylor College of Medicine, where we also conducted our clinical trials.

In 2021, we validated an additional manufacturing site (now Cell Ready) for our multiTAA-specific T cell products.

On June 26, 2023, we completed the transaction with Cell Ready, LLC, or Cell Ready, pursuant to a Purchase Agreement, or the Cell Ready Purchase Agreement, dated May 1, 2023, by and between us and Cell Ready.

Pursuant to the Cell Ready Purchase Agreement, effective as of the Closing Date, we (i) assigned to Cell Ready the leases for our two manufacturing facilities in Houston, Texas, or the Manufacturing Facilities, (ii) sold to Cell Ready all of the equipment and leasehold improvements at the Manufacturing Facilities and (iii) assigned to Cell Ready our rights, title and interest in any contracts related to the equipment and Manufacturing Facilities (collectively referred to as the “Purchased Assets”).

Cell Ready acquired the Purchased Assets for total consideration of $19.0 million.

On February 22, 2024, we entered into a Master Services Agreement for Product Supply, or MSA, with Cell Ready.

Cell Ready, which is owned by one of our directors and shareholders, Mr.

John Wilson, is a contract development and manufacturing organization (CDMO).

Under the MSA, it is anticipated Cell Ready will perform a wide variety of services for us, including research and development, and manufacturing in support of our clinical trials.

Pursuant to the MSA, the Company may contract with Cell Ready for the provision of various products and services from time to time by entering into work orders with Cell Ready.

If the services involve the supply of product, Cell Ready is required to supply such product in conformance with the product requirements set forth in the applicable work order(s).

Under the MSA, Cell Ready is to use only personnel with sufficient qualifications and experience to supply the services contemplated by the MSA, provide its personnel with adequate training and assume full responsibility for its personnel’s compliance with the MSA.

Further, Cell Ready is required to provide the Company with assistance and cooperation in order for the Company to obtain and maintain all necessary regulatory approvals, at the Company’s expense.

We face competition from numerous pharmaceutical and biotechnology companies, as well as from academic institutions, private and public research institutions, and government agencies.

Treatment of relapsed patients with lymphoma remains a challenge with relatively low overall survival rates.

To date, there are four CD19-directed CAR T cell therapies (Yescarta, Kymriah, Tecartus, and Bryanzi) approved for patients with relapsed lymphoma.

However, up to 60% of CD19 CAR T cell treated patients will relapse, particularly in the third line setting (Chong EA et al, N Engl J Med, 2021).

This highlights a significant unmet medical need for alternative and more effective treatments.

Our multiTAA-specific T cell drug candidates may compete with product candidates from a number of companies, which are developing various types of immunotherapies to treat cancer, including non-CD19 targeting CAR T cells that target different antigens beyond CD19, multi-targeted CAR T cells as well as NK-CAR therapies.

In addition, bispecific antibodies represent promising therapies for patients with lymphoma and provide competition in the oncology space.

To date, MT-601 is the only natural T cell product that targets multiple tumor antigens being explored for CAR relapse patients with lymphoma.

Therefore, MT-601 fills a void in the market by providing much needed treatment option to the lymphoma patient population.

We believe that our non-engineered T cell therapy approaches will be synergistic and may improve therapies being developed by potential competitors.

Many companies and institutions, either alone or together with their collaborative partners, have substantially greater financial, technical and human resources, and significantly greater experience than we do in the following:

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● other classes of therapeutic agents.

We face, and will continue to face, intense competition from other companies for collaborative arrangements with pharmaceutical and biotechnology companies, for establishing relationships with academic and research institutions and for licenses to drug candidates or proprietary technology.

We face, and will continue to face, competition from other companies for collaborative arrangements with pharmaceutical and biotechnology companies, for establishing relationships with academic and research institutions and for licenses to drug candidates or proprietary technology.

These competitors, either alone or with their collaborative partners, may succeed in developing products that are more effective than ours.

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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:

9,364,523 (estimated expiration date March 17, 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.

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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In the case of employees, the agreements provide that all inventions conceived by an employee shall be our exclusive property.

We currently have pending with the USPTO applications for registration of the trademarks POLYSTART and “Marker Therapeutics.” We currently have the trademark “TapImmune” registered with the USPTO.

We also have rights to use other names essential to our business.

We currently have pending with the USPTO applications for registration of the trademarks “Marker Therapeutics.” We also have rights to use other names essential to our business.

Federally registered trademarks have a perpetual life if they are maintained and renewed on a timely basis and used properly as trademarks, subject to the rights of third parties to seek cancellation of the trademarks if they claim priority or confusion of usage.

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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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As of December 31, 2023, we had 8 full-time employees.

There were 54 in research, development, quality, CMC and clinical and 13 were in finance, legal, human resources or administrative support.

There were 6 in clinical and 2 were in administrative support.

None of our employees is subject to a collective bargaining agreement.

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We strive to create a diverse environment, and our commitment to diversity, equity and inclusion begins with our leadership team of diverse backgrounds and experiences.

Approximately 90% of our executive officers are women or self-identify as a member of an underrepresented minority group.

100% of our executive officers are women or self-identify as a member of an underrepresented minority group.

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.

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

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.” Our principal executive offices are located at 9350 Kirby Drive, Suite 300, Houston, Texas 77054, 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