What changed in this filing

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Item 1. Business

2025-03-28 compared with 2024-03-11 · 194 added, 263 removed, 373 unchanged (55% of the section changed)

Mustang Bio, Inc.

(“Mustang,” “we,” “us,” “our” or the “Company”) is a clinical-stage biopharmaceutical company focused on translating today’s medical breakthroughs in cell and gene therapies into potential cures for hematologic cancers, solid tumors and rare genetic diseases.

(“Mustang,” “we,” “us,” “our” or the “Company”) is a clinical-stage biopharmaceutical company focused on translating today’s medical breakthroughs into potential cures for difficult-to-treat cancers and autoimmune diseases.

We aim to acquire rights to these technologies by licensing or otherwise acquiring an ownership interest in the technologies, funding their research and development and eventually either out-licensing or bringing the technologies to market.

Our pipeline is currently focused in three core areas:

CAR T therapies for hematologic malignancies, CAR T therapies for solid tumors and gene therapies for rare genetic disorders.

For each therapy we have partnered with world class research institutions.

For our CAR T therapies we have partnered with the City of Hope National Medical Center (“COH” or “City of Hope”), Fred Hutchinson Cancer Center (“Fred Hutch”), Nationwide Children’s Hospital (“Nationwide”) and the Mayo Foundation for Medical Education and Research (“Mayo Clinic”).

For our gene therapies, we have partnered with St.

Jude Children’s Research Hospital (“St.

Jude”) and with Leiden University Medical Centre (“LUMC”) in the development of first-in-class ex vivo lentiviral (“LV”) treatments for X-linked severe combined immunodeficiency (“XSCID”) and RAG1 severe combined immunodeficiency (“RAG1-SCID”), respectively.

Our pipeline is currently focused in two core areas:

CAR T therapies for autoimmune diseases and hematologic malignancies and CAR T therapies for solid tumors.

For these therapies we have partnered with world class research institutions, including the City of Hope National Medical Center (“COH” or “City of Hope”), Fred Hutchinson Cancer Center (“Fred Hutch”), and Nationwide Children’s Hospital (“Nationwide”).

CAR T Therapies

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Our strategy is to license these technologies, support preclinical and clinical research activities by our partners and transfer the underlying technology to our or our contract manufacturer’s cell processing facility in order to conduct our own clinical trials.

We are developing CAR T therapy for hematologic malignancies in partnership with Fred Hutch targeting CD20 (MB-106).

In May 2021, we announced that the U.S.

Food and Drug Administration (“FDA”) accepted our Investigational New Drug (“IND”) Application for MB-106.

As of December 2023, approximately 40 patients have been treated in an ongoing phase 1 clinical trial sponsored by Fred Hutch (ClinicalTrials.gov Identifier:

NCT03277729), and approximately 20 patients have been treated in an ongoing phase 1 clinical trial sponsored by us (ClinicalTrials.gov Identifier:

NCT05360238).

In 2023, we received Safety Review Committee approval to continue dose escalation in all three active arms of the ongoing Mustang-sponsored phase 1 trial.

We presented the latest results, demonstrating a favorable safety profile, complete response rate, and durability, from the ongoing Mustang-sponsored phase 1 trial at the 2023 American Society of Hematology (“ASH”) Annual Meeting.

As of December 31, 2023, the MB-106 Mustang-sponsored phase 1 trial is pending one patient to complete the final dose level required to advance to phase 2 pivotal studies for treatment of patients with relapsed or refractory indolent B-cell non-Hodgkin lymphoma.

We are also developing CAR T therapy for solid tumors in partnership with COH targeting IL13Rα2 (MB-101).

We are developing CAR T therapy for solid tumors in partnership with COH targeting IL13Rα2 (MB-101).

In addition, we have partnered with Nationwide for a herpes simplex virus type 1 (“HSV-1”) oncolytic virus (MB-108) in order to enhance the activity of MB-101 for the treatment of patients with high-grade malignant brain tumors.

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A Phase 1 clinical trial sponsored by the University of Alabama at Birmingham (“UAB”) for MB-108 (ClinicalTrials.gov Identifier:

NCT03657576) began during the third quarter of 2019.

NCT03657576) has also completed the treatment phase and patients continue to be assessed for long-term safety.

In October 2023, we announced that the FDA accepted our IND application for the combination of MB-101 and MB-108 – which is referred to as MB-109 – for the treatment of patients with IL13Rα2+ relapsed or refractory glioblastoma (“GBM”) and high-grade astrocytoma.

Finally, we are collaborating with the Mayo Clinic to develop a novel technology that may be able to transform the administration of CAR T therapies and potentially be used as an off-the-shelf therapy.

We are evaluating plans to file an IND application for a multicenter Phase 1 clinical trial once a lead construct has been identified, subject to allocation of resources.

On May 18, 2023, we announced a series of changes resulting from a review of our portfolio of product candidates to determine the future strategy of our programs and the proper allocation of our resources.

Following this review, we determined to discontinue development of our MB-102 (CD123), MB-103 (HER2), MB-104 (CS1) and MB-105 (PSCA) programs (such programs, the “Discontinued Programs”), all of which were CAR T therapies being developed in partnership with City of Hope.

Gene Therapies

In partnership with St.

Jude, our XSCID gene therapy programs (MB-117 and MB-217) are being developed under an exclusive license to develop a potentially curative treatment for XSCID, a rare genetic immune system condition in which affected patients do not live beyond infancy without treatment.

For these programs, the same lentiviral vector (LVV) will be used to transduce patients’ hematopoietic stem cells ex vivo.

However, since the respective cell processing is different for each cell product, the FDA considers them different products, and we have therefore assigned a different designation to each:

MB-117 designates the cell product for newborn patients, and MB-217 designates the cell product for previously transplanted patients.

The LVV used for MB-117 and MB-217 has been modified from a predecessor LVV in order to address concerns regarding detection of an increased percentage of clones in patients’ myeloid lineage following treatment with the predecessor products (designated MB-107 and MB-207, respectively) engineered using the predecessor LVV.

Although a safety signal has not been observed in over 40 patients treated with the two predecessor products, nevertheless, out of an abundance of caution, we and our academic partners decided to replace the predecessor LVV with the modified LVV.

We anticipate that the NIH and St.

Jude will initiate phase 1 trials in newborn and previously transplanted patients, respectively, in 2024 using the modified LVV to produce MB-117 and MB-217, respectively.

The predecessor LVV has been utilized in two Phase 1/2 clinical trials involving two different autologous cell products produced via transduction of patients’ hematopoietic stem cells.

As noted above, these cell products were designated MB-107 and MB-207, and the respective Phase 1/2 clinical trials were:

a multicenter trial of the MB-107 product in newly diagnosed infants sponsored by St.

Jude (ClinicalTrials.gov Identifier:

NCT01512888) and a single-center trial of the MB-207 product in previously transplanted patients sponsored by the National Institutes of Health (“NIH”) (ClinicalTrials.gov Identifier:

Pursuant to termination of the lease of our cell processing facility in Worcester, MA, we are exploring with COH and Nationwide the possibility of initiating this clinical trial as an investigator-sponsored single-institution study at COH in the fourth quarter of 2025.

We are also developing CAR T therapy for hematologic malignancies and autoimmune diseases in partnership with Fred Hutch targeting CD20 (MB-106).

In May 2021, we announced that the U.S.

Food and Drug Administration (“FDA”) accepted our Investigational New Drug (“IND”) Application for MB-106.

As of March 1, 2025, 53 patients have been treated in an ongoing Phase 1 clinical trial sponsored by Fred Hutch (ClinicalTrials.gov Identifier:

NCT03277729) and 20 patients have been treated in the Phase 1 clinical trial sponsored by us (ClinicalTrials.gov Identifier:

NCT05360238).

In January 2021, we received a safe to proceed “approval” from the FDA for our MB-107 IND application allowing us to initiate a pivotal non-randomized multicenter Phase 2 clinical trial of MB-107 in newly diagnosed infants with XSCID who are under the age of two.

In January 2022, the FDA issued a clinical hold, pending additional Chemistry, Manufacturing and Controls (“CMC”) data, on our IND application to allow for the initiation of a pivotal non-randomized multicenter Phase 2 clinical trial of MB-207 in previously transplanted XSCID patients.

In 2022, the NIH study was suspended as a result of the study stopping rules triggered by the increased percentage of clones noted above.

Jude elected to voluntarily place their study on hold in April 2023, and we elected to voluntarily discontinue development of MB-107 and MB-207 in favor of MB-117 and MB-217 prior to treating any patients with either predecessor product.

Jude and NIH intend to initiate their respective studies of MB-117 and MB-217 in 2024 following availability of the modified LVV.

MB-110, a first-in-class ex vivo treatment for RAG1 SCID, is currently being evaluated at LUMC in a Phase 1/2 multicenter clinical trial in Europe.

In 2022 the first patient was treated without any complications, after which the patient developed a functioning immune system which responded well to the standard vaccinations for newborns.

In 2024, we expect that additional centers will be added and that additional patients will be enrolled.

In 2023, we received Safety Review Committee approval to continue dose escalation in all three active arms of the ongoing Mustang-sponsored Phase 1 trial.

We presented the latest results, demonstrating a favorable safety profile, complete response rate, and durability, from the ongoing Mustang-sponsored Phase 1 trial at the 2023 American Society of Hematology (“ASH”) Annual Meeting.

Pursuant to termination of the lease for our cell processing center in Worcester, MA, we are exploring with Fred Hutch the possibility of initiating a Phase 1 trial in autoimmune diseases as an investigator-sponsored single-institution study at Fred Hutch in the fourth quarter of 2025.

MB-109 (Combination of MB-101 CAR T Therapy with MB-108 Oncolytic Virus Therapy for Malignant Brain Tumors)

In October 2023, we received a safe-to-proceed letter from the FDA for our MB-109 IND application allowing us to initiate a Phase 1, open-label, non-randomized, multicenter study of MB-109 in patients with IL13Rα2+ recurrent GBM and high-grade astrocytoma.

In this Phase 1 clinical study, we intend to evaluate the combination of CAR-T cells (MB-101) and the herpes simplex virus type 1 oncolytic virus (MB-108) in patients with IL13Rα2+ high-grade gliomas.

The design of this study involves first a lead-in cohort, wherein patients are treated with MB-101 alone without prior MB-108 administration.

After successful confirmation of the safety profile of MB-101 alone, the study will then investigate increasing doses of intratumorally administered MB-108 followed by dual intratumoral (ICT) and intraventricular (ICV) administration of MB-101.

On November 7, 2024, we announced that the FDA granted Orphan Drug Designation to Mustang for MB-108, a herpes simplex virus type 1 (“HSV-1”) oncolytic virus, for the treatment of malignant glioma.

The Orphan Drug Designation provides certain incentives, such as tax

credits toward the cost of clinical trials upon approval and prescription drug user fee waivers.

If a product receives Orphan Drug Status from the FDA, that product is entitled to seven years of market exclusivity for the disease in which it has Orphan Drug Designation, which is independent from intellectual property protection.

We are currently exploring with COH and Nationwide the possibility of conducting an investigator-sponsored single-institution trial under the COH IND to treat patients with IL13Rα2+ recurrent GBM and high-grade astrocytoma with MB-109 that could potentially be initiated in the fourth quarter of 2025.

Because cell processing for MB-101 will revert back to COH – where the product continues to be manufactured today for other investigator-sponsored clinical trials being conducted by COH in malignant brain tumors (NCT04003649, NCT04661384, NCT04510051), we believe that it is reasonable to assume that the FDA will not require the aforementioned lead-in cohort.

Should this, indeed, be the case, the first patient enrolled will receive the combination of MB-101 and MB-108, which will represent a considerable savings of time and money – as well as afford the potential benefit of both therapies to every patient treated on study

MB-106 (CD20-targeted CAR T cell therapy for Non-Hodgkin Lymphoma, Chronic Lymphocytic Leukemia and Autoimmune Diseases)

In the first quarter of 2024, we completed a successful End-of-Phase 1 meeting with the FDA regarding a potential pivotal Phase 2 single-arm clinical trial for the treatment of WM.

Per the discussions, the FDA agreed with the proposed overall design of the pivotal trial for Waldenstrom macroglobulinemia (“WM”) at the recommended dose of 1 x 10 7 CAR-T cells/kg and requested only minimal modifications to the study protocol.

No additional nonclinical studies are expected prior to Phase 2 or a Biologics License Application (“BLA”) filing, although the need for additional nonclinical studies after completion of Phase 2 and prior to submission of a BLA is subject to discussions with FDA.

Due to limited resources, and as a result of the reduction in work force described below, we do not expect to initiate our pivotal Phase 2 single-arm clinical trial of MB-106 for the treatment of WM trial in 2025.

Subject to available funds, we intend to rely on third party service providers to conduct study and manufacturing services to advance our priority potential product candidates.

Also in the first quarter of 2024, we completed enrollment of the indolent lymphoma arm in our multicenter Phase 1 trial.

The tenth and final patient enrolled on that arm was a patient with follicular lymphoma (FL) who achieved a complete response following treatment with 1 x 10 7 CAR-T cells/kg.

As a result, the overall complete response rate for FL in the Phase 1 portion of this trial was sustained at 100% (N=6), with no occurrence of cytokine release syndrome (“CRS”) above grade 1 and no immune effector cell-associated neurotoxicity syndrome (“ICANS”) of any grade, despite not using prophylactic tocilizumab or dexamethasone.

In March 2024, we announced plans to collaborate with Fred Hutch for a proof-of-concept Phase 1 investigator-sponsored clinical trial evaluating MB-106 in autoimmune diseases.

In March 2024, we were granted the Regenerative Medicine Advanced Therapy (“RMAT”) designation by the FDA for the treatment of relapsed or refractory CD20 positive WM and FL, based on potential improvement in response as seen in clinical data to date.

Drugs eligible for RMAT designation are those intended to treat, modify, reverse or cure a serious or life-threatening disease or condition, and that present preliminary clinical evidence indicating the drug has the potential to address unmet medical needs for such disease or condition.

RMAT designation provides regenerative medicine advanced therapy products with the same benefits to expedite the development and review of a marketing application that are available to drugs that receive Breakthrough Therapy Designation.

These advantages include timely advice and interactive communications with FDA, as well as proactive and collaborative involvement by senior FDA managers and experienced review and regulatory health project management staff.

A product designated as an RMAT also may be eligible for other FDA-expedited programs, such as Priority Review.

The FDA also may conduct a rolling review of products in its expedited programs, reviewing portions of a marketing application before the complete application is submitted.

In June 2024, we announced that updated data for MB-106 in the Phase 1/2 Fred Hutch investigator-sponsored trial showed a favorable safety and efficacy profile in 10 patients with WM.

There was an overall response rate (“ORR”) of 90% with durable responses observed, including three complete responses (“CR”), two very good partial responses (“VGPR”), and four partial responses (“PR”).

One of the patients who achieved a CR remained in remission for 31 months, with an immunoglobulin M (IgM) level that decreased rapidly to the normal range after treatment with MB-106 and remained normal since.

Patients had a median of nine prior lines of therapy, and only one patient started additional anti-WM treatment after being treated with MB-106.

From a safety perspective, CRS occurred in nine patients:

five patients with grade 1 and four patients with grade 2.

One patient experienced grade 1 ICANS.

No grade 3 or 4 CRS or grade 2, 3 or 4 ICANS was observed, despite dose escalation.

In May 2024, we informed the clinical sites participating in the Mustang-sponsored Phase 1/2 study in non-Hodgkin lymphoma and chronic lymphocytic leukemia, MB106-CD20-001, that we had decided to close the trial.

In June 2024, we similarly informed the clinical sites participating in the Mustang-sponsored Long-term Follow-up Study in Patients Previously Treated with Mustang Bio, Inc.

CAR-T Cell Investigational Products, MB100-OBS-001, that we had decided to close that trial.

As a result, further clinical development of MB-106 is

currently focused solely on autoimmune diseases unless funding and resources become available to restart the program for hematologic malignancies.

Planning for the aforementioned Phase 1 investigator-sponsored clinical trial in autoimmune diseases is in progress, with initiation of the trial planned for 2025.

To date, we have not received approval for the sale of any of our product candidates in any market and, therefore, have not generated any product sales from our product candidates.

In addition, we have incurred substantial operating losses since our inception and expect to continue to incur significant operating losses for the foreseeable future and may never become profitable.

As of December 31, 2023, we have an accumulated deficit of $381.0 million.

As of December 31, 2024, we had an accumulated deficit of $396.7 million.

We are a majority-controlled subsidiary of Fortress Biotech, Inc.

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We were incorporated in Delaware on March 13, 2015.

Our executive offices are located at 377 Plantation Street, Worcester, Massachusetts 01605.

Our executive offices are located at 95 Sawyer Road, Suite 110, Waltham, Massachusetts 02453.

Our telephone number is (781) 652-4500, and our email address is info@mustangbio.com .

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Therapies for Oncology and Hematologic Malignancies

MB-106 (CD20 CAR T for B cell non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia (CLL))

We believe CD20 is a promising target for immunotherapy of B-cell malignancies.

CD20 is a B-cell lineage-specific phosphoprotein that is expressed in high, homogeneous density on the surface of more than 95% of B-cell NHL and CLL.

CD20 is stable on the cell surface with minimal shedding, internalization, or modulation upon antibody binding and is present at only nanomolar levels as a soluble antigen.

It is well established as an effective immunotherapy target, with extensive studies demonstrating improved tumor responses and survival of B-NHL patients treated with rituximab and other anti-CD20 antibodies.

Importantly, CD20 continues to be expressed on the lymphoma cells of most patients with relapsed B-NHL despite repetitive rituximab treatments, and loss of CD20 expression is not a major contributor to treatment resistance.

Thus, there is strong rationale for testing CD20 CAR T cells as an immunotherapy for NHL.

More than 80,000 new cases of NHL are diagnosed each year in the United States, and over 20,000 patients die of this group of diseases annually.

Most forms of NHL, including follicular lymphoma, mantle cell lymphoma, marginal zone lymphoma, lymphoplasmacytic lymphoma, and small lymphocytic lymphoma (“SLL”), which account collectively for approximately 45% of all cases of NHL, are incurable with available therapies, except for allogenic stem cell transplant (“allo-SCT”).

However, many NHL patients are not suitable candidates for allo-SCT, and this treatment is also limited by significant rates of morbidity and mortality due to graft-versus-host disease.

Aggressive B-cell lymphomas such as diffuse large B-cell lymphoma, the most common subtype of lymphoma, account for an additional 30-35% of NHL.

The majority of patients with aggressive B-NHL are successfully treated with combination chemotherapy, but a significant proportion relapse or have refractory disease, and the outcome of these patients is poor.

Innovative new treatments are therefore urgently needed.

Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) is a mature B cell neoplasm characterized by a progressive accumulation of monoclonal B lymphocytes.

CLL is considered to be identical (i.e., one disease with different manifestations) to the NHL SLL.

The malignant cells seen in CLL and SLL have identical pathologic and immunophenotypic features.

The term CLL is used when the disease manifests primarily in the blood, whereas the term SLL is used when involvement is primarily nodal.

CLL is the most common leukemia in adults in Western countries, accounting for approximately 25 to 35 percent of all leukemias in the United States.

An estimated 20,700 new cases of CLL will be diagnosed in the United States in 2024.

CLL is considered to be mainly a disease afflicting older adults, with a median age at diagnosis of approximately 70 years;

however, it is not unusual to make this diagnosis in younger individuals (e.g., from approximately 30 to 39 years of age).

The incidence increases rapidly with increasing age.

The natural history of CLL is extremely variable, with survival times from initial diagnosis that range from approximately 2 to 20 years, and a median survival of approximately 10 years.

Most patients will have a complete or partial response to initial therapy.

However, conventional therapy for CLL is not curative and most patients experience relapse.

In addition, many patients will require a change in therapy due to intolerance.

Since patients with CLL are generally elderly with a median age older than 70 years, and due to the relatively benign course of the disease in the majority of patients, only selected patients are candidates for intensive treatments such as allo-SCT.

Innovative new treatments with a favorable safety profile are therefore urgently needed for patients with relapsed and refractory disease.

Under their IND, Fred Hutch is currently conducting a Phase 1/2 clinical study to evaluate the anti-tumor activity and safety of administering CD20-directed third-generation CAR T cells incorporating both 4-1BB and CD28 co-stimulatory signaling domains (MB-106) to patients with relapsed or refractory B-cell NHL or CLL (ClinicalTrials.gov Identifier:

NCT03277729).

Secondary endpoints of this study include safety and toxicity, preliminary antitumor activity as measured by overall response rate and complete remission rate, progression-free survival, and overall survival.

The study is also assessing CAR T cell persistence and the potential immunogenicity of the cells.

Finally, this study was designed so that, together with Fred Hutch, we could determine a recommended Phase 2 dose.

Fred Hutch intends to enroll approximately 50 subjects in this study, which is being led by the Principal Investigator Mazyar Shadman, M.D., M.P.H., Associate Professor of Fred Hutch’s Clinical Research Division.

The Fred Hutch IND was amended in 2019 to incorporate an optimized manufacturing process that had been developed in collaboration with us.

In May 2021, we announced that the FDA issued a safe to proceed letter for our IND application allowing for initiation of a multi-center Phase 1/2 clinical study of MB-106 in patients with relapsed or refractory B cell NHL or CLL (Clinicaltrials.gov Identifier:

NCT05360238).

In August 2022, the first patient was treated in our study.

In November 2021, Mustang was awarded a grant of approximately $2.0 million from NCI of the National Institutes of Health.

This two-year award partially funded the Mustang-sponsored multicenter trial to assess the safety, tolerability and efficacy of MB-106.

In August 2023, we fully utilized the grant.

In June 2022, MB-106 received Orphan Drug Designation for the treatment of Waldenstrom macroglobulinemia (“WM”).

In December 2023, Mustang presented preliminary clinical data for the indolent lymphoma patients treated in the ongoing Phase 1/2 clinical study at the American Society of Hematology (ASH) annual meeting.

All 9 patients responded clinically to treatment;

the observed overall response rate was 100%.

All 5 follicular lymphoma patients achieved a complete response.

Among the WN patients 1 patient attained a very good partial response, and 2 patients attained a partial response.

The single patient with a hairy cell leukemia variant experienced stable disease.

The safety profile demonstrated that MB-106 was well tolerated with no occurrences of cytokine release syndrome (“CRS”) above grade 1, and no immune effector cell-associated neurotoxicity syndrome (“ICANS”) of any grade was reported.

Cell expansion and persistence were also demonstrated.

In the first quarter of 2024, the Company expects to receive FDA feedback in an End-of-Phase 1 Meeting on its strategy to conduct a non-randomized registrational multicenter trial in relapsed or refractory WM.

In the second half of 2024, the Company expects to treat the first patient in that trial, which could enable top-line results in the second half of 2026.

In order to facilitate interactions with the FDA throughout this process, we anticipate requesting Regenerative Medicine Advanced Therapy (‘RMAT’) designation for indolent lymphoma – which includes WM – from the FDA in the first half of 2024.

We are currently evaluating the extent to which we can continue the development of MB-106 in other NHL subtypes, subject to allocation of resources.

Combination MB-101(IL13Rα2 CAR T Cell Program for Glioblastoma) and MB-108 (HSV-1 oncolytic virus C134) as a Potential Treatment for IL13Rα2+ Relapsed or Refractory Glioblastoma (GBM) and High-Grade Astrocytoma.

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The design of this study involves first a lead in cohort, wherein patients are treated with MB-101 alone without prior MB-108 administration.

We are currently evaluating the extent to which we can initiate this study, subject to allocation of resources.

After successful evaluation of the safety profile of MB-101 alone, the study will then investigate increasing doses of intratumorally administered MB-108 followed by dual intratumoral (ICT) and intraventricular (ICV) administration of MB-101.

We are currently exploring with COH and Nationwide the possibility of conducting an investigator-sponsored single-institution trial under the COH IND to treat patients with IL13Ra2+ recurrent GBM and high-grade astrocytoma with MB-109 that could potentially be initiated in the fourth quarter of 2025.

The Orphan Drug Designation provides certain incentives, such as tax credits toward the cost of clinical trials upon approval and prescription drug user fee waivers.

If a product receives Orphan Drug Status from the FDA, that product is entitled to seven years of market exclusivity for the disease in which it has Orphan Drug designation, which is independent from intellectual property protection.

MB-101 (IL13Rα2 CAR T Cell Program for Glioblastoma)

GBM is the most common brain and central nervous system (“CNS”) cancer, accounting for approximately 49.1% of malignant primary brain and CNS tumors, approximately 54% of all gliomas, and approximately 16% of all primary brain and CNS tumors.

More than 14,490 new GBM cases were predicted to be diagnosed in the U.S.

Malignant brain tumors are the second leading cause of cancer-related deaths in adolescents and young adults aged 15-39 and the most common cancer occurring among 15-19-year-olds in the U.S.

While GBM is a rare disease 2-3 cases per 100,000 persons per year in the U.S.

and European Union (“EU”), it is quite lethal, with five-year survival rate historically under 10%, which has been virtually unchanged for decades.

Standard of care therapy consists of maximal surgical resection,

radiation, and chemotherapy with temozolomide, which, while rarely curative, is shown to extend median overall survival from 4.5 to 15 months.

GBM remains difficult to treat due to the inherent resistance of the tumor to conventional therapies.

GBM is the most common brain and central nervous system (“CNS”) cancer, accounting for approximately 52% of malignant primary brain and CNS tumors and approximately 14% of all primary brain and CNS tumors.

On average during the years 2017 through 2021, more than 13,000 new cases of GBM were diagnosed per year in the U.S.

While GBM is a rare disease, with only 3.3 cases per 100,000 persons per year in the U.S., it is quite lethal, with a median survival of only 9 months.

Standard of care therapy for patients less than 70 years of age consists of maximal surgical resection, radiation, chemotherapy with temozolomide, and alternating electric field therapy.

This front-line regimen has remained relatively unchanged for the last 20 years due to the failure of novel therapies to improve survival, and there is no standard of care whatsoever for recurrent GBM.

Immunotherapy approaches targeting brain tumors offer promise over conventional treatments.

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however, the patient’s disease eventually recurred at four new locations that were distinct and non-adjacent to the original tumors, and biopsy of one of these lesions showed decreased expression of IL13Rα2.

Results from this COH study have laid the foundation for three new MB-101 studies:

Results from this COH study have laid the foundation for three MB-101 studies that are currently enrolling patients and one possible combination study in the future:

MB-101 with or without nivolumab and ipilimumab in treating patients with recurrent or refractory glioblastoma (currently enrolling patients;

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NCT04661384) sponsored by COH;

MB-101 in treating children with recurrent or refractory IL13Rα2 positive brain tumors (currently enrolling patients;

ClinicalTrials.gov Identifier:

NCT04510051) sponsored by COH;

MB-101 in combination with the herpes simplex virus type 1 oncolytic virus (MB108) in treating patients with recurrent or refractory glioblastoma or high-grade astrocytoma, as described above.

This combination therapy, to be administered in a phase 1 two-center trial under our IND, will be referred to as MB-109.

We refer to this combination therapy as MB-109, and we are currently exploring with COH and Nationwide the possibility of conducting a Phase 1 trial with this therapy to treat patients with these poor-prognosis malignant brain tumors.

This trial would be an investigator-sponsored single-institution trial under the COH IND and could potentially be initiated in the fourth quarter of 2025

MB-108 (HSV-1 oncolytic virus C134)

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In addition to this direct oncolytic activity, the virus promotes an immune response against surviving tumor cells, which increases the antitumor effect of the therapy.

The virus expresses a gene from another virus from the same overall virus family, human cytomegalovirus, which allows it to replicate better

in the tumor cells than its first-generation predecessors.

The virus expresses a gene from another virus from the same overall virus family, human cytomegalovirus, which allows it to replicate better in the tumor cells than its first-generation predecessors.

However, the virus has also been genetically engineered to minimize the production of any toxic effects for the patient receiving the therapy.

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These effects cumulatively should result in converting an immunologically cold tumor to an immunologically hot tumor, which we anticipate will increase the efficacy of our IL13Rα2-directed CAR T for the treatment of GBM and high-grade astrocytoma.

The O’Neal Comprehensive Cancer Center at the UAB is the single clinical trial site for the Phase 1 trial of MB-108, and this site has initiated a Phase 1 trial that began enrolling patients in 2019 (ClinicalTrials.gov Identifier:

NCT03657576).

The O’Neal Comprehensive Cancer Center at the UAB is the single clinical trial site for the first Phase 1 trial of MB-108.

This site initiated in 2019 (ClinicalTrials.gov Identifier:

NCT03657576) and, after enrolling 19 patients, has completed the treatment phase, and patients continue to be assessed for long-term safety.

The primary objective of this study is to determine the safety and tolerability of a single dose of MB-108 administered via a stereotactic intracerebral injection and to determine the maximally tolerated dose (“MTD”) of the oncolytic virus.

Secondary objectives are to obtain preliminary information about the potential benefit of MB-108 in the treatment of patients with recurrent malignant gliomas, including relevant data on markers of efficacy, including time to tumor progression and patient survival.

As of April 2023, 9 patients had been enrolled in this study.

In Vivo CAR T Platform Technology

We are collaborating with the Mayo Clinic to develop a novel technology that may be able to transform the administration of CAR T therapies and potentially be used as an off-the-shelf therapy.

The technology, developed by Larry R.

Pease, Ph.D., principal investigator and former director of the Center for Immunology and Immune Therapies at Mayo Clinic, is a new platform to administer CAR T therapy using a two-step approach.

First, a peptide is administered to the patient to drive the proliferation of the patient’s resident T cells.

This is followed by the administration of a viral CAR construct directly into the lymph nodes of the patient.

In turn, the viral construct infects the activated T cells and effectively forms CAR T cells in vivo in the patient.

Successful implementation may lead to an off-the-shelf product with no need to isolate and expand patient T cells ex vivo in a cell processing facility.

Preclinical proof-of-concept has been established, and the ongoing development of this technology will take place at Mayo Clinic.

We are evaluating plans to file an IND application for a multicenter Phase 1 clinical trial once a lead construct has been identified, subject to allocation of resources.

Gene Therapies for Rare Genetic Disorders

MB-117 and MB-217 (designation of MB-107 and MB-207, respectively, following replacement of the predecessor LVV with a modified LVV) (Ex vivo Lentiviral Therapy for X-linked Severe Combined Immunodeficiency (XSCID))

XSCID is a rare genetic immune system condition that occurs almost exclusively in males, in which affected patients do not live beyond infancy without treatment.

Mustang Bio’s first-in-class ex vivo lentiviral gene therapy for XSCID has been administered as two distinct cellular products using the same predecessor lentiviral vector in two phase 1/2 clinical trials:

(1) a multicenter trial of MB-107 in newly diagnosed patients being led by St.

Jude and including also UCSF Benioff Children’s Hospital San Francisco (“UCSF”) and Seattle Children’s Hospital (“Seattle Children’s”) (ClinicalTrials.gov Identifier:

NCT01512888) and (2) a single center trial of MB-207 at the NIH in patients who have previously undergone hematopoietic stem cell transplantation (ClinicalTrials.gov Identifier:

Results from this trial were used to determine the dose of MB-108 approved by the FDA for combination with MB-101 in the treatment of patients with IL13Rα2+ recurrent GBM and high-grade astrocytoma under the originally proposed Mustang IND multicenter trial.

We believe that the same doses of both therapies will be appropriate for the Phase 1 investigator-sponsored single-institution combination trial currently under discussion with COH and Nationwide.

Also listed on ClinicalTrials.gov are two additional Phase 1 trials at UAB involving MB-108 administered as a single agent to patients with recurrent malignant glioma:

(1) a trial designed to determine safety and tolerability of administering a second dose of MB-108 to patients who previously completed the aforementioned first-in-human 19-patient Phase 1 trial (ClinicalTrials.gov Identifier:

enrolling by invitation) and (2) a trial that contemplates two treatments of 1 x 10 5 plaque forming units (PFU) each, with the timing and qualification for the second treatment outlined in detail by the protocol (ClinicalTrials.gov Identifier:

not yet recruiting)..

MB-106 (CD20 CAR T for B cell non-Hodgkin lymphoma (NHL), chronic lymphocytic leukemia (CLL) and autoimmune diseases)

We believe CD20 is a promising target for immunotherapy of B-cell malignancies.

CD20 is a B-cell lineage-specific phosphoprotein that is expressed in high, homogeneous density on the surface of more than 95% of B-cell NHL and CLL.

CD20 is stable on the cell surface with minimal shedding, internalization, or modulation upon antibody binding and is present at only nanomolar levels as a soluble antigen.

Thus, there is strong rationale for testing CD20 CAR T cells as an immunotherapy for NHL.

NCT03277729).

In 2022, the NIH study was suspended as a result of the study stopping rules triggered by the increased percentage of clones in patients’ myeloid lineage, as noted above.

All patients treated in the St.

Jude and NIH clinical trials continue to be followed and remain clinically stable with no significant hematological anomalies, including no observations of insertional mutagenesis and/or malignancies.

Jude and NIH intent to initiate their respective studies of MB-117 and MB-217 in 2024 following availability of the modified LVV.

As part of addressing concerns relating to clonal expansion, the joint team existing of St.

Jude, UCSF, Seattle Children’s and the NIH decided to suspend use of the primary lentiviral vector.

Going forward, this predecessor LV vector will be replaced by a modified LV vector which will be used to produce the MB-117 and MB-217 cell products.

St Jude has informed us that it intends to initiate a new Phase 1 trial in newly diagnosed infants using MB-117, and the NIH has informed us that it intends to initiate a new Phase 1 trial in previously transplanted patients using MB-217, each in 2024.

MB-110 (Ex vivo Lentiviral Therapy for RAG1 Severe Combined Immunodeficiency (SCID))

Under an exclusive license and in partnership with LUMC, MB-110, a first-in-class ex vivo treatment for RAG1 SCID, is under development.

Severe combined immunodeficiency (“SCID”) due to complete recombinase-activating gene-1 (RAG1) deficiency is a rare, genetic disorder due to null mutations in the RAG1 gene resulting in less than 1% of wild type V(D)J recombination activity.

Neonatal patients present with life-threatening, severe, recurrent infections by opportunistic fungal, viral and bacterial micro-organisms, as well as skin rashes, chronic diarrhea, failure to thrive and fever.

Immunologic observations include profound T and B cell lymphopenia, low or absent serum immunoglobulins, and normal natural killer cell counts.

As is the case with other types of SCID, RAG1-SCID is fatal in infancy unless immune reconstitution is achieved with hematopoietic stem cell transplantation (HSCT).

MB-110, which includes low-dose conditioning prior to reinfusion of the patients’ own gene-modified blood stem cells, is currently being evaluated in a Phase 1/2 multicenter clinical trial in Europe.

The ongoing clinical trial has enrolled its first patient, and additional clinical sites are expected to be added in the near future.

The RAG1-SCID program has been granted Orphan Drug Designation by the European Medicines Agency.

We also established an ongoing partnership with Frank J.

Staal, Ph.D., professor of Molecular Stem Cell Biology and molecular immunologist at LUMC, whose laboratory developed the MB-110 therapy.

Staal will continue the development of additional LV gene therapies in his lab, to which we have certain rights under the agreement.

The study is also assessing CAR T cell persistence and the potential immunogenicity of the cells.

Finally, this study was designed so that, together with Fred Hutch, we could determine a recommended Phase 2 dose.

The Fred Hutch IND was amended in 2019 to incorporate an optimized manufacturing process that had been developed in collaboration with us.

NCT05360238).

In August 2022, the first patient was treated in our study.

In November 2021, Mustang was awarded a grant of approximately $2.0 million from NCI of the National Institutes of Health.

This two-year award partially funded the Mustang-sponsored multicenter trial to assess the safety, tolerability and efficacy of MB-106.

In August 2023, we fully utilized the grant.

In June 2022, MB-106 received Orphan Drug Designation for the treatment of Waldenstrom macroglobulinemia (“WM”).

All 9 patients responded clinically to treatment;

the observed overall response rate was 100%.

All 5 follicular lymphoma patients achieved a complete response.

Among the WN patients 1 patient attained a very good partial response, and 2 patients attained a partial response.

The single patient with a hairy cell leukemia variant experienced stable disease.

The safety profile demonstrated that MB-106 was well tolerated with no occurrences of CRS above grade 1, and no ICANS of any grade was reported.

Cell expansion and persistence were also demonstrated.

In the first quarter of 2024, we completed a successful End-of-Phase 1 meeting with the FDA regarding a potential pivotal Phase 2 single-arm clinical trial for the treatment of WM.

Per the discussions, the FDA agreed with the proposed overall design of the pivotal trial for WM at the recommended dose of 1 x 10 7 CAR-T cells/kg and requested only minimal modifications to the study protocol.

Subject to available funds, we intend to rely on third party service providers to conduct study and manufacturing services to advance our priority potential product candidates.

Also in the first quarter of 2024, we completed enrollment of the indolent lymphoma arm in our multicenter Phase 1 trial.

The tenth and final patient enrolled on that arm was a patient with follicular lymphoma (FL) who achieved a complete response following treatment with 1 x 10 7 CAR-T cells/kg.

As a result, the overall complete response rate for FL in the Phase 1 portion of this trial was sustained at 100% (N=6), with no occurrence of CRS above grade 1 and no ICANS of any grade, despite not using prophylactic tocilizumab or dexamethasone.

In March 2024, we announced plans to collaborate with Fred Hutch for a proof-of-concept Phase 1 investigator-sponsored clinical trial evaluating MB-106 in autoimmune diseases.

In June 2024, we announced that updated data for MB-106 in the Phase 1/2 Fred Hutch investigator-sponsored trial showed a favorable safety and efficacy profile in 10 patients with WM.

One of the patients

who achieved a CR remained in remission for 31 months, with an immunoglobulin M (IgM) level that decreased rapidly to the normal range after treatment with MB-106 and remained normal since.

Patients had a median of nine prior lines of therapy, and only one patient started additional anti-WM treatment after being treated with MB-106.

From a safety perspective, CRS occurred in nine patients:

five patients with grade 1 and four patients with grade 2.

One patient experienced grade 1 ICANS.

No grade 3 or 4 CRS or grade 2, 3 or 4 ICANS was observed, despite dose escalation.

In June 2024, we similarly informed the clinical sites participating in the Mustang-sponsored Long-term Follow-up Study in Patients Previously Treated with Mustang Bio, Inc.

CAR-T Cell Investigational Products, MB100-OBS-001, that we had decided to close that trial.

As a result, further clinical development of MB-106 is currently focused solely on autoimmune diseases unless funding and resources become available to restart the program for hematologic malignancies.

Planning for the aforementioned Phase 1 investigator-sponsored clinical trial in autoimmune diseases is in progress, with initiation anticipated in the fourth quarter of 2025.

Terminated Product Candidates (CAR-T Therapies, Gene Therapies and in vivo CAR-T)

We previously developed four additional CAR-T product candidates licensed from City of Hope, which included MB-102 (CD123), MB-103 (HER2), MB-104 (CS1) and MB-105 (PSCA) programs.

In May 2023, we announced a series of changes resulting from a review of our portfolio of product candidates to determine the future strategy of our programs and the proper allocation of our resources.

Following this review, we determined to discontinue development of these four programs and terminated the associated license agreements.

In addition, we previously developed several gene therapy product candidates, which included MB-117 and MB-217 (based on technologies licensed from St.

Jude Children’s Research Hospital (“St.

Jude”)) and MB-110 (based on technologies licensed from Leiden University Medical Centre (“LUMC”)).

In April 2024, we entered into a termination and release agreement with St.

Jude, pursuant to which we agreed to terminate the license agreement underpinning the MB-117 and MB-217 product candidates in exchange for a mutual release of liability and forgiveness by St.

Jude of all amounts previously owing to them.

Also in April 2024, we delivered a termination notice to LUMC pursuant to which we terminated the license agreement underpinning the MB-110 product candidate;

we are currently in discussions with LUMC regarding the terms that will govern such termination.

In June 2024, we also agreed with Mayo Foundation for Medical Education and Research (“Mayo Clinic”) to terminate the license agreement underpinning our (now former) preclinical in vivo CAR-T program, together with a related sponsored research agreement, in exchange for a mutual release of liability and forgiveness by Mayo Clinic of all amounts previously owed to them.

INTELLECTUAL PROPERTY AND PATENTS

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Patents maturing from these national stage applications will expire no sooner than March 2037.

In March 2017, we licensed intellectual property related to antibodies and binding agents that specifically bind to PSCA from the University of California Los Angeles (“UCLA”).

In August 2023, we terminated the license agreement with UCLA.

In August 2018, we licensed from St.

Jude Children’s Research Hospital XSCID Technology related to an ex vivo lentiviral vector gene therapy program to provide a normal copy of the IL2RG gene to patients born with XSCID.

In February 2019, we licensed material and technical information related to the HSV-1 oncolytic virus C134 from Nationwide in Columbus, Ohio.

In August 2019, we licensed from CSL Behring (Calimmune) the Cytegrity TM stable producer cell line developed and used by St.

The Cytegrity TM stable producer cell line was developed in order to be used to produce the viral vector for MB-107 and MB-207.

However, the decision to modify the LVV used to transduce the hematopoietic stem cells of XSCID patients and thereby replace MB-107 and MB-207 with MB-117 and MB-217, respectively, rendered the stable producer cell no longer useful.

Therefore, on August 14, 2023, we notified Calimmune that we were terminating the Calimmune license, which took effect 60 days following notification.

In September 2020, we entered into an exclusive, worldwide licensing agreement with SIRION Biotech for the rights to SIRION’s LentiBOOST TM technology for the development of MB-207.

This license includes right to granted patents and pending applications in the U.S., Europe, Japan, and Israel.

In December 2021 this licensing agreement was amended to include CD20-directed CAR Ts in addition to lentiviral stem cell gene therapy for the treatment of XSCID.

We eventually expect to use this technology for the development of MB-217.

In November 2021, we entered into an exclusive, worldwide licensing agreement with Leiden University Medical Centre for a first-in-class ex vivo lentiviral gene therapy for the treatment of RAG1 severe combined immunodeficiency (“RAG1-SCID”).

In August 2021, we entered into an exclusive license agreement with Mayo Clinic for a novel technology that may be able to transform the administration of CAR T therapies and potentially allow such therapies to be used as an off-the-shelf therapy.

In addition to the technology we have in-licensed, we also developed our own proprietary intellectual property, both alone and in conjunction with COH.

In particular, we filed a U.S.

provisional application directed to optimized methods for manufacturing cell-based therapeutics, and we and COH, as co-applicants, filed a U.S.

provisional application directed to methods of treating hematological cancers.

In addition to the technology we have in-licensed, we have also developed our own proprietary intellectual property, both alone and in conjunction with COH.

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LICENSE, CLINICAL TRIAL AND SPONSORED RESEARCH AGREEMENTS

Jude Children’s Research Hospital

XSCID License

On August 2, 2018, we entered into an exclusive worldwide license agreement with St.

Jude for the development of a first-in-class ex vivo lentiviral gene therapy for the treatment of XSCID.

We paid $1.0 million in consideration for the exclusive license in addition to an annual maintenance fee of $0.1 million (beginning in 2019).

Jude is eligible to receive payments totaling $13.5 million upon the achievement of five development and commercialization milestones.

Royalty payments in the mid-single digits are due on net sales of licensed products (e.g.

MB-117 and MB-217).

XSCID Non-interventional Services Agreement

In December 2019, we entered into a Non-Interventional Services Agreement with Children's CGMP, LLC (“Children’s”), an affiliate of St.

Jude Children's Research Hospital, pursuant to which Children’s provides lentiviral vector for non-clinical XSCID research purposes, as well as related advisory services, and we agreed to fund approximately $0.8 million upon execution.

XSCID Data Transfer Agreement

In June 2020, we entered into a Data Transfer Agreement for the XSCID program (the “XSCID DTA”).

Pursuant to the terms of the XSCID DTA, we made an upfront payment of approximately $1.1 million and will reimburse St.

Jude for additional costs in connection with the on-going investigator-initiated study.

City of Hope National Medical Center

In February 2017, we and COH amended and restated our license agreement, dated March 17, 2015 (the “Original COH Agreement”), by entering into three separate amended and restated exclusive license agreements, one relating to the CD123-directed CAR T program, one relating to the IL13Rα2-directed CAR T program, and one relating to the Spacer technology (described below).

As of December 31, 2023, COH owns 845,385 shares of our Class A common stock, which are convertible into 56,359 shares of Common Stock, and has the right to appoint a member to our Board of Directors (the “Board”).

As of March 2025, COH owns 845,385 shares of our Class A common stock, which are convertible into 1,127 shares of Common Stock, and has the right to appoint a member to our Board of Directors (the “Board”) until the tenth anniversary, March 15, 2025.

In addition, we entered into a sponsored research agreement with COH under which we have funded continued research in the amount of $2.0 million per year, payable in four equal installments, which ended in the first quarter of 2020.

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Following this review, we determined to discontinue development of the Discontinued Programs, which included a portion of our portfolio of CAR T therapies being developed by us in partnership with the City of Hope.

Following this review, we determined to discontinue development of the four CAR-T Therapies licensed from City of Hope listed above under “Terminated Product Candidates.”

IL13Rα2 License

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Royalty payments in the low-single digits are due on net sales of licensed products.

University of California License

On March 17, 2017, we entered into an exclusive license agreement with the Regents of UCLA (the “UCLA License”) to acquire intellectual property rights in patent applications related to the engineered anti-prostate stem cell antigen antibodies for cancer targeting and detection.

Pursuant to the UCLA License, we paid UCLA an upfront fee of $0.2 million and owed annual maintenance fees.

In addition, UCLA was eligible to receive milestone payments totaling up to $14.3 million, and royalty payments in the mid-single digits are due on net sales of licensed products.

On July 10, 2023, we notified UCLA that we were terminating the UCLA license, which took effect on August 9, 2023.

Fred Hutchinson Cancer Center

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Royalty payments in the low-single digits are due on net sales of licensed products.

CSL Behring (Calimmune) License

On August 23, 2019, we entered into a non-exclusive license agreement with CSL Behring (Calimmune) for the Cytegrity TM stable producer cell line for the production of lentiviral gene therapy for the XSCID gene therapy program.

The Cytegrit TM stable producer cell line was used to produce the predecessor LVV for our MB-107 and MB-207 lentiviral gene therapies for the treatment of XSCID.

We paid $0.2 million in consideration for the license.

CSL Behring (Calimmune) was eligible to receive additional payments totaling $1.2 million upon the achievement of development and commercialization milestones.

Royalty payments in the low-single digits were due on net sales of licensed products.

Therefore, on August 14, 2023, we notified Calimmune that we were terminating the Calimmune license, which took effect 60 days following notification.

SIRION Biotech License

On October 6, 2020, we announced a licensing agreement under which we acquired technology rights from SIRION Biotech GmbH (“SIRION”) for LentiBOOST™ technology for the development of MB-207, our predecessor lentiviral gene therapy for the treatment of patients with XSCID, who have been previously treated with a hematopoietic stem cell transplantation (“HSCT”) and for whom re-treatment is indicated.

LentiBOOST™ is SIRION’s proprietary non-cytotoxic transduction enhancer for lentiviral vectors.

We eventually expect to use this technology for the development of MB-217, the cell product that uses a modified LVV to transduce the hematopoietic stem cells of patients previously treated with an HSCT.

Pursuant to the agreement, we paid SIRION a one-time upfront fee of $0.1 million.

In addition, SIRION is eligible to receive additional payments totaling up to approximately $9.1 million upon the achievement of certain development and commercialization milestones.

Royalty payments in the low- to mid-single digits are due on aggregate cumulative worldwide net sales of licensed products.

In December 2021, this licensing agreement was amended to include CD20-directed CAR Ts.

SIRION is eligible to receive additional payments totaling up to approximately $9.1 million upon the achievement of certain development and commercialization milestones for the additional product.

Mayo Foundation for Medical Education and Research

CAR T Technology License

On August 12, 2021, we announced that we executed an exclusive license agreement with Mayo Clinic for a novel technology that may be able to transform the administration of CAR T therapies and potentially allow such therapies to be used as an off-the-shelf therapy.

The technology, developed by Larry R.

Pease, Ph.D., principal investigator and former director of the Center for Immunology and Immune Therapies at Mayo Clinic, is a new platform to administer CAR T therapy using a two-step approach.

First, a peptide is administered to the patient to drive the proliferation of the patient’s resident T cells.

This is followed by the administration of a viral CAR construct directly into the lymph nodes of the patient.

In turn, the viral construct infects the activated T cells and effectively forms CAR T cells in vivo in the patient.

Successful implementation may lead to an off-the-shelf product with no need to isolate and expand patient T cells ex vivo.

Preclinical proof-of-concept has been established, and the ongoing development of this technology will take place at Mayo Clinic.

We are evaluating plans to file an IND application for a multicenter Phase 1 clinical trial once a lead construct has been identified, subject to allocation of resources.

Pursuant to this agreement, we paid an upfront fee of $0.8 million and will pay an annual maintenance fee of $25,000.

Additional payments are due for each of two licensed products upon the achievement of development and commercial milestones totaling up to $92.6 million per product, and royalty payments in the mid-single digits are due on net sales of licensed products.

Sponsored Research Agreement

In connection with the RAG1-SCID license, we entered into an SRA with LUMC under which we fund research supporting the program in the amount of 2.3 million euros over a period of five years.

Competition in the pharmaceutical and biotechnology industries is intense.

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The field of CAR T therapy is extremely active.

Companies and partnerships currently engaged in clinical trials with CAR T modalities include Bristol Myers Squibb, Novartis, AstraZeneca, Janssen Pharmaceutical Company, Gilead Sciences, Galapagos NV, Autolus Therapeutics, 2seventy bio, Kyverna Therapeutics, CARGO Therapeutics, ImmPACT Bio, and Cabaletta Bio.

The gene therapy field is characterized by rapidly changing technologies, significant competition and a strong emphasis on intellectual property.

We are aware of companies currently engaged in developing gene therapies in various indications, including Abeona Therapeutics, Adverum Biotechnologies, Astellas, AVROBIO, Sio Gene, Biogen, bluebird bio, BioMarin Pharmaceutical, Krystal Biotech, MeiraGTx, Novartis Pharmaceuticals, Orchard Therapeutics, Passage Bio, Prevail Therapeutics, REGENXBIO, Rocket Pharmaceuticals, Roche, Sangamo Therapeutics, Sarepta Therapeutics, Solid Biosciences, Ultragenyx Pharmaceuticals, uniQure and Voyager Therapeutics, as well as several companies addressing other methods for delivering or modifying genes and regulating gene expression.

Companies and partnerships currently engaged in clinical trials with CAR T modalities include Bristol Myers Squibb, Novartis, AstraZeneca, Janssen Pharmaceutical Company, Legend Biotech, Gilead Sciences, Arcellx, Galapagos NV, Autolus Therapeutics, 2seventy bio, Kyverna Therapeutics, ImmPACT Bio, TG Therapeutics, and Cabaletta Bio.

As of December 31, 2024, we had 6 full-time employees.

None of our employees is represented by a labor union or covered under a collective bargaining agreement, and we consider our employee relations to be good.

Employees of Fortress also make valuable financial, legal, scientific and other strategic contributions to our Company on a regular basis.

Employees of Fortress also make valuable financial, legal, business development, scientific and other strategic contributions to our Company on a regular basis.

SUPPLY AND MANUFACTURING

As an early-stage development company, we rely on our research partners to manufacture or have manufactured all LV vectors used in the clinical development programs currently in progress at COH, Fred Hutch, St.

Jude, the NIH, and LUMC under the IND applications filed by these institutions.

In addition, we rely on the NIH to produce oncolytic virus for UAB, the clinical trial site for the Phase 1 trial of Nationwide’s herpes simplex virus type 1 oncolytic virus (MB-108).

We will continue to rely on our research partners to manufacture lentiviral vectors and oncolytic virus for our IND trials until such time as material is available from our contract manufacturing organizations.

In addition, we rely on the NIH to produce oncolytic virus for the aforementioned UAB Phase 1 trials of Nationwide’s herpes simplex virus type 1 oncolytic virus (MB-108), and potentially as well for the Phase 1 investigator-sponsored single-institution MB-109 combination trial currently under discussion with COH and Nationwide.

Pursuant to the March 2015 Licensing Agreement with COH, we have the right to make and have made the cellular products, and we have negotiated Investigator-Initiated Clinical Research Support Agreements with COH and Fred Hutch which specify the cell processing costs and numbers of patients which will be supplied under filed protocols.

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We have limited experience in processing cells for clinical or commercial purposes.

In 2018, we opened our own cell processing facility in Worcester, Massachusetts, in order to manufacture and supply cellular product candidates for all clinical trials that will be conducted under IND applications to be filed by us.

In May 2023, we entered into an Asset Purchase Agreement with uBriGene (Boston) Biosciences, Inc., pursuant to which we agreed to sell our leasehold interests in our cell processing facility and associated assets relating to the manufacturing and production of cell and gene therapies.

In 2018, we opened our own cell processing facility in Worcester, Massachusetts, in order to manufacture and supply cellular product candidates for all clinical trials that would be conducted under IND applications to be filed by us.

In May 2023, we entered into an Asset Purchase Agreement (the “Prior Asset Purchase Agreement”) with uBriGene (Boston) Biosciences, Inc.

(“uBriGene”), pursuant to which we agreed to sell our leasehold interests in our cell processing facility and associated assets relating to the manufacturing and production of cell and gene therapies.

On July 28, 2023, we completed the sale of all of our assets relating to our operations primarily relating to the manufacturing and production of cell and gene therapies.

See “Management’s Discussion and Analysis of Financial Condition and Results of Operations – Recent Developments.”

In May 2021, the FDA accepted our IND to initiate a multi-center Phase 1/2 clinical trial of MB-106 (CD20) under our IND.

In October 2023, the FDA accepted our IND application to initiate a Phase 1 clinical trial of MB-109.

As with any supply program, obtaining raw materials of the correct quality cannot be guaranteed, and we cannot ensure that we will be successful in this endeavor.

We expect to rely on contract manufacturing relationships for LV vectors and for the MB-108 oncolytic virus, as well as for any non-CAR T products that we may in-license or acquire in the future for co-administration with our CAR T products.

In June 2024, we entered into an Asset Purchase Agreement with uBriGene to repurchase the assets, properties and rights previously transferred by the Company to uBriGene under the Prior Asset Purchase Agreement, excluding any inventory transferred under the Prior Asset Purchase Agreement that has been consumed or transferred to a third party by uBriGene since the closing of the Prior Asset Purchase Agreement.

Finally, on February 7, 2025, we entered into the First Amendment to the lease agreement with WCS - 377 Plantation Street, Inc., pursuant to which the lease was terminated, which became effective on February 21, 2025.

On February 27, 2025, we announced the relocation of our corporate headquarters to 95 Sawyer Road, Waltham, Massachusetts.

Going forward, we expect to continue to rely on our academic partners and future contract manufacturing relationships to support cell processing for clinical trials of our CAR T products.

Furthermore, we expect to rely on contract manufacturing relationships for LV vectors and for the MB-108 oncolytic virus, as well as for any non-CAR T products that we may in-license or acquire in the future.

However, there can be no assurance that we will be able to successfully contract with such manufacturers on terms acceptable to us, or at all.

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None of our product candidates has been approved for sale in any market.

Before marketing in the U.S.,

any drug that we develop must undergo rigorous pre-clinical testing and clinical trials and an extensive regulatory approval process implemented by the FDA under the FDCA.

Before marketing in the U.S., any drug that we develop must undergo rigorous pre-clinical testing and clinical trials and an extensive regulatory approval process implemented by the FDA under the FDCA.

The FDA regulates, among other things, the pre-clinical and clinical testing, safety, efficacy, approval, manufacturing, record keeping, adverse event reporting, packaging, labeling, storage, advertising, promotion, export, and the sale and distribution of biopharmaceutical products.

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Products that are eligible for fast track, RMAT or breakthrough therapy designation may be eligible to receive a priority review if the criteria for priority review are met at the time of the BLA or NDA submission.

In addition, studied for their safety and effectiveness in treating serious or life-threatening illnesses and that provide meaningful therapeutic benefit over existing treatments may receive accelerated approval.

Approval is determined on the basis of adequate and well-controlled clinical trials that establishing that the drug has an effect on a surrogate endpoint that is reasonably likely to predict clinical benefit, or on a clinical endpoint that can be measured earlier than irreversible morbidity or mortality, that is reasonably likely to predict an effect on irreversible morbidity or mortality or other clinical benefit, taking into account the severity, rarity or prevalence of the condition and the

availability or lack of alternative treatments.

In addition, drugs studied for their safety and effectiveness in treating serious or life-threatening illnesses and that provide meaningful therapeutic benefit over existing treatments may receive accelerated approval.

As a condition of approval, the FDA may require a sponsor of a drug receiving accelerated approval to perform post-marketing studies to verify and describe the predicted effect on irreversible morbidity or mortality or other clinical endpoint and under the Food and Drug Omnibus Reform Act of 2022 (FDORA), the FDA is now permitted to require, as appropriate, that such trials be underway prior to approval or within a specific time period after the date of approval for a product granted accelerated approval.

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These guidelines relate to, among other things:

preclinical evaluation of gene therapies, design of clinical studies, and the chemistry, manufacturing and control information that should be included in an initial IND application and throughout clinical development to support a NDA or BLA application.

Measures to observe for delayed adverse effects in subjects who have been exposed to investigational gene therapies are required.

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Pharmaceutical Coverage, Pricing and Reimbursement

and markets in other countries, sales of any products for which we receive regulatory approval for commercial sale will depend in part on the availability of reimbursement from third-party payors, including government health administrative authorities, managed care providers, private health insurers and other organizations.

Third-party payors are increasingly examining the medical necessity and cost-effectiveness of medical products and services, in addition to their safety and efficacy, and, accordingly, significant uncertainty exists as to the reimbursement status of newly approved therapeutics.

Adequate third-party reimbursement may not be available for any product for which we obtain regulatory approval to enable us to realize an appropriate return on our investment in research and product development.

We are unable to predict the future course of federal or state health care legislation and regulations, including regulations that will be issued to implement provisions of the health care reform legislation enacted in 2010, known as the Affordable Care Act.

The Affordable Care Act and further changes in the law or regulatory framework could have a material adverse effect on our business.

The ability to successfully commercialize any product candidate which receives marketing authorization depends in part on the extent to which coverage and reimbursement for these products and related treatments will be available from government health administration authorities, private health insurers and other organizations.

Government authorities and other third-party payors, such as private health insurers and health maintenance organizations, decide which medications they will pay for and establish reimbursement levels.

A primary trend in the healthcare industry in the United States and elsewhere is cost containment.

The United States and many foreign jurisdictions have enacted or proposed legislative and regulatory changes affecting the healthcare system, including implementing cost-containment programs to limit the growth of government-paid healthcare costs, including price controls, restrictions on reimbursement and requirements for substitution of generic products for branded prescription drugs.

In the United States, the Affordable Care Act was intended to broaden access to health insurance, reduce or constrain the growth of healthcare spending, enhance remedies against fraud and abuse, add transparency requirements for the healthcare and health insurance industries, impose new taxes and fees on the health industry and impose additional health policy reforms.

There have been significant ongoing judicial, administrative, executive and legislative efforts to modify or eliminate the Affordable Care Act.

Changes to and under the Affordable Care Act remain possible but it is unknown what form any such changes or any law proposed to replace or revise the Affordable Care Act would take, and how or whether it may affect our business in the future.

We expect that changes to the Affordable Care Act, the Medicare and Medicaid programs, changes allowing the federal government to directly negotiate drug prices and changes stemming from other healthcare reform measures, especially with regard to healthcare access, financing or other legislation in individual states, could have a material adverse effect on the healthcare industry.

We also expect that the Affordable Care Act, as well as other healthcare reform measures that have and may be adopted in the future, may result in more rigorous coverage criteria and in additional downward pressure on the price that can be charged for drug products.

Any reduction in reimbursement from Medicare, Medicaid, or other government programs may result in a similar reduction in payments from private payers.

The Inflation Reduction Act of 2022 (the “IRA”) contains substantial drug pricing reforms, including the establishment of a drug price negotiation program within the U.S.

Department of Health and Human Services that would require manufacturers to charge a negotiated “maximum fair price” for certain selected drugs or pay an excise tax for noncompliance, the establishment of rebate payment requirements on manufacturers of certain drugs payable under Medicare Parts B and D to penalize price increases that outpace inflation, and requires manufacturers to provide discounts on Part D drugs.

Orphan drugs that treat only one rare disease are exempt from the IRA’s drug negotiation program.

Substantial penalties can be assessed for noncompliance with the drug pricing provisions in the IRA.

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.

Additional federal, state and foreign healthcare reform measures will be adopted in the future, any of which could limit the amounts that federal and state governments will pay for healthcare products and services, which could result in limited coverage and reimbursement and reduced demand or additional pricing pressures.

These and other healthcare reform measures that may be adopted in the future may result in more rigorous coverage criteria and in additional downward pressure on the price that we receive for any current product or future product candidate.

Any reduction in reimbursement from Medicare or other government healthcare programs may result in a similar reduction in payments from private payors.

The implementation of cost containment measures or other healthcare reforms may prevent us from being able to generate revenue, attain profitability or commercialize our products.

Legislative and regulatory proposals have been made to expand post-approval requirements and restrict sales and promotional activities for drugs.

It is uncertain whether additional legislative changes will be enacted, or whether the FDA regulations, guidance or interpretations will be changed, or what the impact of such may be.

In addition, increased Congressional scrutiny of the FDA’s approval process may significantly delay or prevent marketing approval, as well as subject the industry to more stringent product labeling and post-marketing testing and other requirements.

It is also unclear what impact any changes made by the new presidential administration will have on the industry.

Such actions may impact the development and commercialization of drug products.

International Regulation

2 unchanged sentences

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