What changed in this filing

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Item 1. Business

2022-03-23 compared with 2021-03-24 · 151 added, 76 removed, 573 unchanged (28% of the section changed)

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Our pipeline is currently focused in three core areas:

gene therapy programs for rare genetic disorders, chimeric antigen receptor (“CAR”) engineered T cell (“CAR T”) therapies for hematologic malignancies and CAR T therapies for solid tumors.

gene therapies for rare genetic disorders, chimeric antigen receptor (“CAR”) engineered T cell (“CAR T”) therapies for hematologic malignancies and CAR T therapies for solid tumors.

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

For our gene therapy programs, we have partnered with St.

For our gene therapies, we have partnered with St.

Jude Children’s Research Hospital (“St.

Jude”) in the development of a first-in-class ex vivo lentiviral treatment of X-linked severe combined immunodeficiency (“XSCID”) and for our CAR T therapies we have partnered with the City of Hope National Medical Center (“COH”), Fred Hutchinson Cancer Research Center (“Fred Hutch”) and Nationwide Children’s Hospital (“Nationwide”).

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

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

Gene Therapies

In partnership with St.

Jude, our gene therapy program is being conducted 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.

Jude, our XSCID gene therapy programs (MB-107 and MB-207) are being conducted 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.

This first-in-class ex vivo lentiviral gene therapy is currently in two Phase 1/2 clinical trials involving two different autologous cell products:

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

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

Jude and a single-center

trial of the MB-207 product in previously transplanted patients sponsored by the National Institutes of Health (“NIH”).

In January 2021 we received approval to proceed with our Investigational New Drug (“IND”) application with the U.S.

Food and Drug Administration (“FDA”) 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.

We plan to file an IND application in the second quarter of 2021 in order to conduct a pivotal non-randomized multicenter Phase 2 clinical trial of MB-207 in previously transplanted XSCID patients.

Food and Drug Administration (“FDA”) 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 hold, pending Chemistry, Manufacturing and Controls (“CMC”) clearance, on our IND application to conduct a pivotal non-randomized multicenter Phase 2 clinical trial of MB-207 in previously transplanted XSCID patients.

CAR T Therapies

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In the third quarter of 2019 the FDA approved our IND application to initiate a multi-center Phase 1/2 clinical trial of MB-102, and our clinical trial began enrollment in 2020 for the treatment of patients with blastic plasmacytoid dendritic cell neoplasm.

We expect to file an IND for MB-106 in the first quarter of 2021 and to initiate our own Phase 1/2 clinical trial shortly thereafter for the treatment of patients with non-Hodgkin lymphoma and chronic lymphocytic leukemia.

In May 2021, the FDA approved our IND application to initiate a multi-center Phase 1/2 clinical trial of MB-106, and we expect to begin the treatment of patients with non-Hodgkin lymphoma and chronic lymphocytic leukemia in the first half of 2022.

We plan to file an IND for a multicenter Phase 1/2 trial for MB-104 for the treatment of patients with multiple myeloma once COH has established a safe and effective dose.

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Phase 1 clinical trials sponsored by COH for MB-101, MB-103 and MB-105 are underway.

A Phase 1 clinical trial sponsored by the University of Alabama at Birmingham (“UAB”) for MB-108 began during the third quarter of 2019 and, in the fourth quarter of 2021, we plan to file an IND for the combination of MB-101 and MB-108 for the treatment of patients with GBM.

A Phase 1 clinical trial sponsored by the University of Alabama at Birmingham (“UAB”) for MB-108 began during the third quarter of 2019 and, in the second half of 2022, we plan to file an IND for the combination of MB-101 and MB-108 – which is referred to as MB-109 – for the treatment of patients with relapsed or refractory GBM and anaplastic astrocytoma,.

In the third quarter of 2019, we announced that COH had started enrolling patients on a Phase 1 clinical trial of MB-101 in combination with nivolumab (commercial name:

Opdivo ® ) and ipilimumab (commercial name:

Yervoy ® ) in patients with recurrent malignant glioma (ClinicalTrials.gov Identifier:

NCT04003649).

In the fourth quarter of 2020 we announced that COH had initiated a Phase 1, two-arm clinical trial of MB-101 in patients with leptomeningeal brain tumors (e.g., glioblastoma, ependymoma or medulloblastoma;

ClinicalTrials.gov Identifier:

NCT04003649).

We also plan to file INDs and initiate our own clinical trials for MB-103 for the treatment of patients with metastatic breast cancer to brain and for MB-105 for the treatment of patients with prostate and pancreatic cancer.

Finally, the Company is 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.

Mustang plans to file an IND application for a multicenter Phase 1 clinical trial once a lead construct has been identified.

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

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PRODUCTS UNDER DEVELOPMENT

Gene Therapy for Rare Genetic Disorders

Gene Therapies for Rare Genetic Disorders

MB-107 and MB-207 (Ex vivo Lentiviral Therapy for X-linked Severe Combined Immunodeficiency (XSCID))

XSCID is a rare genetic immune system condition also known as bubble boy disease, in which affected patients do not live beyond infancy without treatment.

This first-in-class ex vivo lentiviral gene therapy has already been given to 24 patients in two early stage clinical trials, with highly encouraging results.

Eleven patients under the age of two years were treated at St.

Jude and UCSF Benioff Children’s Hospital San Francisco,

with results presented at the 61st Annual Meeting of the American Society of Hematology (“ASH”) in December 2020 (ClinicalTrials.gov Identifier:

NCT01512888), and thirteen patients 3 to 34 years of age were treated in a single-center trial at the NIH (ClinicalTrials.gov Identifier:

NCT01306019), with results presented at that same ASH meeting in December 2019 .

The existing data from these 24 patients are encouraging.

In the initial Phase 1/2 NIH trial, eight patients (referred to as Cohort A) were followed for 3 to 7 years.

Mustang Bio’s first-in-class ex vivo lentiviral gene therapy for XSCID is currently being administered as two distinct cellular products using the same 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:

NCT01306019).

The most recent peer-reviewed presentations by the respective investigators for these two trials occurred at the 61st Annual Meeting of the American Society of Hematology (“ASH”) in December 2019, at which time 24 patients had been treated in total.

Eleven patients under the age of two years had been treated at St.

Jude and UCSF and thirteen patients 3 to 34 years of age had been treated at the NIH .

The existing data from these 24 patients were encouraging.

In the initial stage of accrual to the Phase 1/2 NIH trial, eight patients (referred to as Cohort A) were followed for 3 to 7 years.

Among Cohort A, seven patients aged 3 to 23 years increased host T cells chimerism from 0-2% to 28-93% and had normal T cell proliferation response.

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No evidence of malignant transformation was observed.

Subsequent to the initiation of the NIH trial, eleven patients under two years old who had not previously undergone hematopoietic stem cell transplant (“HSCT”) were treated with the ex-vivo gene therapy in a St.

Jude/UCSF Phase 1/2 trial, resulting in highly encouraging results.

Subsequent to the initiation of the NIH trial, eleven patients under two years old who had not previously undergone hematopoietic stem cell transplantation (“HSCT”) were treated with the ex-vivo gene therapy in a St.

Jude/UCSF/Seattle Children’s Phase 1/2 trial, resulting in highly encouraging results.

Low-dose busulfan conditioning caused non-hematologic adverse events in only two patients (mild mucositis;

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That press release disclosed that all 11 patients enrolled on the St.

Jude/USCF trial continued to do well, and 5 additional patients had been enrolled at the time of the most recent analysis in early September 2020.

Jude/USCF/Seattle Children’s trial continued to do well, and 5 additional patients had been enrolled at the time of the most recent analysis in early September 2020.

At that time, follow-up for these 16 patients ranged from 3 months to 47 months.

Similar to previous reports, the therapy continued to be well tolerated in all patients, and stable vector marking was noted in all lineages, with successful engraftment of genetically-modified T-, B-, & NK-cells.

Similar to previous reports, the therapy continued to be well tolerated in all patients, and stable vector marking was noted in

all lineages, with successful engraftment of genetically-modified T-, B-, & NK-cells.

All patients cleared pre-existing infections, no new severe infections were noted, and all patients were outpatients.

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As was the case in Cohort A, no serious adverse events related to treatment were reported other than hematologic related to low-dose busulfan conditioning, and there was no evidence of malignant transformation.

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

In partnership with LUMC, our RAG1-SCID gene therapy program (MB-110) is being conducted under an exclusive license to develop a first-in-class ex vivo treatment for a rare genetic immune system condition.

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

Patients present with neonatal onset of 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.

Mustang 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 therapy.

Staal will continue the development of additional lentiviral gene therapies in his lab, to which Mustang Bio has rights under the agreement.

CAR T Therapies for Hematologic Malignancies

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The lymph nodes and spleen may also be involved.

Common misdiagnoses for BPCDN include non-Hodgkin lymphoma (“NHL”), AML, leukemia cutis [a nonspecific term used for cutaneous (skin) manifestation of any type of leukemia], melanoma (a type of skin cancer), and lupus erythematosus (chronic

inflammatory disease that occurs when the body’s immune system attacks its own tissues and organs).

There are no data or randomized clinical trials that can define the best first treatment for patients with BPDCN.

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CS1 is overexpressed in multiple myeloma (“MM”) and light chain amyloidosis (“AL”), which makes it a good target for immunotherapy.

A humanized anti-CS1 antibody, elotuzumab (Empliciti™), has shown promising results in clinical studies.

A humanized anti-CS1 antibody, elotuzumab (Empliciti™), has

shown promising results in clinical studies and was initially approved by the FDA in 2015 in combination with lenalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received one to three prior therapies .

Despite great advances in treatment, MM remains an incurable malignancy of plasma cells.

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Once COH has established a safe and effective dose for MB-104 in this trial, we expect to file an IND for a multicenter Phase 1/2 trial for the treatment of patients with MM.

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

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

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

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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 account for 30-35% of NHL.

Aggressive B-cell lymphomas such as diffuse large B-cell 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.

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

Fred Hutch has an open IND for a Phase 1/2 clinical study to evaluate the anti-tumor activity and safety of administering CD20 directed CAR T cells (MB-106) to patients with relapsed or refractory B-cell NHL or chronic lymphocytic leukemia (ClinicalTrials.gov Identifier:

Fred Hutch has an open IND for 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).

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The first patient treated in this cohort had follicular lymphoma that had relapsed after initial therapy, maintenance therapy, and two salvage regimens.

She achieved a complete response (CR) on Day 28, and no cytokine release syndrome or neurologic toxicity was observed.

She achieved a complete response (“CR”) on Day 28, and no cytokine release syndrome (“CRS”) or neurologic toxicity was observed.

While this initial success using the optimized MB-106 process is important, additional clinical testing is necessary, and accrual to the trial continues.

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Data presented by Fred Hutch reported on an initial seven patients treated without response and without significant CAR T cell expansion or persistence.

Among these 7 patients there was one occurrence of cytokine release syndrome (CRS;

Among these 7 patients there was one occurrence of CRS (CRS;

grade 3 – unexplained alkaline phosphatase elevation in the setting of fever), and there were no occurrences of immune effector cell-associated neurotoxicity syndrome (“ICANS”).

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Mustang plans to file an IND at the end of the first quarter of 2021 to enable the initiation of a multicenter Phase 1/2 trial of MB-106.

In December 2021, we announced MB-106 data presented at ASH2021.

Mazyar Shadman of Fred Hutch updated interim data showing a 95% overall response rate, 65% complete response rate and favorable safety profile from the ongoing Phase 1/2 clinical trial for NHL and CLL.

No patient experienced CRS or ICANS ≥ grade 3.

CAR T Therapies for Solid Tumors

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This IND was submitted in October 2014, with COH as the sponsor.

COH has enrolled and treated 65 patients as of December 31, 2020.

COH has enrolled and treated 65 patients as of

December 31, 2021.

In the annual meeting of the American Association for Cancer Research in April 2018, our collaborators at COH presented the preliminary data for patients enrolled on Arm 2 of the protocol (the “Intracavitary Arm”).

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NCT04661384);

MB-101 in combination with the C134 oncolytic virus (MB-108) in treating patients with recurrent or refractory glioblastoma (IND filing expected in the fourth quarter of 2021).

MB-101 in combination with the C134 oncolytic virus (MB-108) in treating patients with recurrent or refractory glioblastoma (IND filing expected in the second half of 2022).

This combination will be referred to as MB-109.

MB-103 (HER2 CAR T for GBM & Metastatic Breast Cancer to Brain)

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While HER2-targeted therapy in combination with conventional agents has shown some promise for the treatment of patients with metastatic breast cancer, control of brain metastases remains a significant unmet clinical need, as most patients survive less than two years following CNS involvement.

Recent advances in cellular immunotherapy approaches have underscored the potential for potent antitumor immune responses and clinical benefit against solid cancers, and these approaches may be effective in the treatment of HER2+ cancers – in particular breast cancer – that have metastasized to

Likewise, HER2 has been suggested as a suitable target for GBM, wherein elevated HER2 protein levels have been correlated with impaired survival.

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this polymorphism is thought to be associated with a risk for certain gastric and bladder cancers.

Prostate cancer may be amenable to T cell-based immunotherapy since several tumor antigens, including prostate stem-cell antigen (“PSCA”), are widely overexpressed in metastatic disease.

Prostate cancer may be

amenable to T cell-based immunotherapy since several tumor antigens, including prostate stem-cell antigen (“PSCA”), are widely overexpressed in metastatic disease.

Our academic partners at COH have developed a second-generation PSCA-specific CAR T cell therapy that has demonstrated robust in vitro and in vivo anti-tumor activity in patient-derived, clinically relevant, bone-metastatic prostate cancer xenograft models.

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This trial has been on clinical hold since October 2020 due to toxicity at the highest dose level, and UAB expects FDA clearance in the first half of 2021 in order to resume enrolling patients at a lower dose level.

As a result of this clinical hold, as well as COVID-19 virus-related accrual delays in 2020, we expect that IND filing for the combination trial of MB-108 with MB-101 will be delayed until the fourth quarter of 2021.

As a result of this clinical hold, as well as COVID-19 virus-related accrual delays in 2020, we expect that IND filing for the combination trial of MB-108 with MB-101 (MB-109) will be delayed until the fourth quarter of 2022.

INTELLECTUAL PROPERTY AND PATENTS

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are maintained in secrecy for a period of 18 months or more.

There is even an opportunity under specific circumstances to keep the contents of patent applications hidden until the patent application matures to an issued patent.

The patent positions of biotechnology and pharmaceutical companies are highly uncertain and involve complex legal and factual questions.

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In March 2015, we licensed intellectual property related to CAR T technology from COH.

The intellectual property licensed thereunder includes two granted U.S.

patents and pending patent applications in a number of countries, including the U.S.

and the EU, as well as pending patent applications in Japan, China, South Korea, Australia and the developing world.

These granted patents include claims directed to nucleic acids and expression vectors encoding CARs targeting IL13Rα2 and CD123.

The granted patents and any patents maturing from these pending applications will expire no sooner than October 2033.

The pending applications in these patent families also include various claims relating to CARs, T cells that express the CARs, methods of treatment utilizing the CAR T cells and additional specific features to optimize administration of CAR T cells, targeting, binding specificity, cell stimulation and persistence.

Additional applications and pending claims from COH that we have rights to include the use of an optimized hinge region for many targeted CAR constructions, along with compositions and methods to isolate and transfect T memory cells to improve cellular persistence, as well as applications and claims related to CS1-, HER2-, and PSCA-targeted CARs.

The portfolio of rights licensed from COH now includes patents and application directed to CARs targeting IL13Rα2, CD123, CS1, HER2, and PSCA, as well as rights related to modified CAR hinge regions and methods of preparing CAR T cells in particular subpopulations of cell and administering CAR T cells.

The intellectual property licensed thereunder relating to IL13Rα2-targeting CARs includes granted patents in the U.S., Australia, China, Europe, Russia, Japan, Hong Kong, Israel, and Mexico, and this patent family further includes pending applications in the U.S., Australia, Brazil, Canada, China, Europe, South Korea, Russia, Japan, Israel, Mexico, and New Zealand.

Any patents issuing from the IL13Rα2-targeting CAR will expire no sooner than 2035.

The licensed intellectual property relating to relating to CD123-targeting CARs includes issues patents in the U.S., China, Europe, Hong Kong, Israel, Japan, South Korea, and Mexico, and this patent family further includes pending applications in the U.S., Australia, Brazil, China, Europe, Hong Kong, Israel, Japan, South Korea, Mexico, and New Zealand.

Any patents issuing from the CD123-targeting CAR will expire no sooner than 2033.

The licensed intellectual property relating to relating to CS1-targeting CARs includes issues patents in the U.S., Australia, Israel, and Russia, as well as pending applications in the U.S., Australia, Brazil, Canada, China, Europe, Hong Kong, Israel, South Korea, Mexico, Japan, Russia, and New Zealand.

Any patents issuing from the CS1-targeting CAR will expire no sooner than 2035, and some patents relating to particular methods involving CS1-targeting CARs will expire no sooner than 2038.

The licensed intellectual property relating to relating to HER2-targeting CARs includes issues patents in Japan and Russia, as well as pending applications in the U.S., Australia, Brazil, Canada, China, Europe, Hong Kong, Israel, Japan, South Korea, Russia, Mexico, and New Zealand.

Any patents issuing from the HER2-targeting CAR will expire no sooner than 2036.

The licensed intellectual property relating to relating to PSCA-targeting CARs includes issues patents in Europe and Hong Kong, as well as pending applications in the U.S., Australia, Brazil, Canada, China, Europe, Hong Kong, Israel, Japan, South Korea, Russia, and New Zealand.

The licensed intellectual property relating to relating modified CAR hinge regions includes issues patents in China, Europe, and Japan, as well as pending applications in the U.S., Australia, China, and Europe.

The patents issuing from the modified CAR hinge region family will expire no sooner than 2034.

The licensed intellectual property relating to relating to method of preparing or administering CAR T cells includes issues patents in China, Europe, and Japan, as well as pending applications in the U.S., Australia, Brazil, Canada, China, Europe, Hong Kong, Japan, Israel, Mexico, Russia, and New Zealand.

The patents relating to these technologies will expire no sooner than 2035 or, in the case of the administration methods, 2036.

Also, in March 2015, we executed a sponsored research agreement with COH, pursuant to which research is performed in the laboratory of Drs.

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In May 2017, we licensed intellectual property related to CAR T technology for targeting CD20 from Fred Hutch.

The intellectual property includes an international application under the Patent Cooperation Treaty (i.e., a PCT application), which has now entered the national stage of multiple countries including the U.S., EU, Japan, China, and Canada, among others.

The intellectual property includes an international application under the Patent Cooperation Treaty (i.e., a PCT application), which has now matured into several issued patents, including issued patents in the U.S.

and Europe, as well as pending applications in the U.S., Australia, Brazil, Canada, China, Europe, Hong Kong, Israel, Japan, South Korea, Mexico, New Zealand, and Russia.

These applications contain claims relating to various CD20-targeting CAR constructs and CAR T cells, as well as methods of making and using the same.

In May 2018, national stage applications claiming priority to the PCT application were filed in several jurisdictions around the world, including the U.S.

and Europe, in order to begin substantive examination of the claims.

The national stage applications claiming priority to the PCT application were filed in May 2018 in order to begin substantive examination of the claims.

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”).

The intellectual property includes multiple granted patents and pending applications from around the world including the U.S., EU, Japan, China, and Canada.

The intellectual property includes multiple granted patents and pending applications from around the world including the U.S., Europe, Japan, China, and Canada.

The granted patents and patents maturing from the pending applications will expire no sooner than March 2027.

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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.

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 the Company has in-licensed, Mustang has also developed its own proprietary intellectual property, both alone and in conjunction with COH.

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provisional application directed to methods of treating hematological cancers.

In addition to the technology the company has in-licensed, Mustang has also developed its own proprietary intellectual property, both alone and in conjunction with COH.

In particular, Mustang owns pending applications in the U.S.

and Europe directed to methods for manufacturing cell-based therapeutics, and pending applications in the U.S., Taiwan, and PCT relating to anti-idiotype antibodies.

Mustang and COH also own as co-applicants pending application in the U.S., Taiwan, and PCT directed to methods of treating hematological cancers with a combination therapy.

Other Intellectual Property Rights

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In addition to patent protection, we may utilize orphan drug regulations or other provisions of the Food, Drug and Cosmetic Act of 1938, as amended (the “FDCA”), to provide market exclusivity for certain of our product candidates.

Orphan drug regulations provide incentives to pharmaceutical and biotechnology companies to develop and manufacture drugs for the treatment of rare diseases, currently defined as diseases that exist in fewer than 200,000 individuals in the U.S., or diseases that affect more than 200,000 individuals in the U.S.

Orphan drug regulations provide incentives to pharmaceutical and biotechnology companies to develop and manufacture drugs for the treatment of rare diseases, currently defined as

diseases that exist in fewer than 200,000 individuals in the U.S., or diseases that affect more than 200,000 individuals in the U.S.

but for which the sponsor does not realistically anticipate will generate a net profit.

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The total potential consideration payable to COH by the Company, in equity or cash, did not in the aggregate change materially from the Original Agreement.

As of December 31, 2020, COH owns 845,385 shares of Class A common stock and 448,203 shares of common stock, representing approximately 1.8% of ownership, and has the right to appoint a director to the Board of Directors (the “Board”).

As of December 31, 2021, COH owns 845,385 shares of Class A common stock representing approximately 0.9% of ownership, and has the right to appoint a director to the Board of Directors (the “Board”).

The Company considers COH to be a related party, due to the foregoing rights and ownership, as well as the high proportion of the Company’s assets that are licensed from COH.

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

The research covered under this arrangement is for the IL13Rα2-directed CAR T program, the CD123-directed CAR T program, and the Spacer technology.

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In February 2017, the Company entered into a Clinical Research Support Agreement for CD123-directed CAR T program (the “CD123 CRA”).

Pursuant to the terms of the CD123 CRA, the Company made an upfront payment of approximately $19,000 and will contribute an

additional $97,000 per patient in connection with the on-going investigator-initiated study.

Pursuant to the terms of the CD123 CRA, the Company made an upfront payment of approximately $19,000 and will contribute an additional $97,000 per patient in connection with the on-going investigator-initiated study.

Further, the Company agreed to fund approximately $76,000 annually pertaining to the clinical development of the CD123-directed CAR T therapy.

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In October 2020, the Company entered into a Sponsored Research Agreement (“SRA”) with COH to conduct combination studies of a potential IL13Rα2 CAR and C134 oncolytic virus therapy.

Pursuant to the SRA, the Company will fund research in the amount of $0.3 million for the program, with an initial term of six months.

Pursuant to the SRA, the Company funded research in the amount of $0.3 million for the program.

Spacer License

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Pursuant to the IV/ICV License, in March 2017, the Company paid COH an upfront fee of $0.1 million.

COH is eligible to receive a milestone payment totaling approximately $0.1 million, upon and subject to the achievement of a milestone, and an annual maintenance fee.

COH is eligible to receive a

milestone payment totaling approximately $0.1 million, upon and subject to the achievement of a milestone, and an annual maintenance fee.

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

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On January 3, 2018, the Company entered into a non-exclusive license agreement with COH to acquire patent and licensed know-how rights related to developing, manufacturing, and commercializing licensed products.

The Company paid $75,000 in consideration for the licenses

to the patent rights and the licensed know-how in addition to an annual maintenance fee.

The Company paid $75,000 in consideration for the licenses to the patent rights and the licensed know-how in addition to an annual maintenance fee.

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

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In connection with the CD20 CTA, the Company agreed to fund up to $5.3 million of costs associated with the clinical trial, which commenced during the fourth quarter of 2017.

In November 2020, the CD20 CTA was amended to include additional funding of approximately $0.8 million for the treatment of five patients with chronic lymphocytic leukemia (“CLL”).

In November 2020, the CD20 CTA was amended to include additional funding of approximately $1.8 million for the treatment of five patients with chronic lymphocytic leukemia (“CLL”) and other research costs.

Sponsored Research Agreement

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

The research performed pursuant to this agreement will support the technology the Company has licensed from LUMC.

Competition in the pharmaceutical and biotechnology industries is intense.

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We are aware of companies currently engaged in developing gene therapies in various indications, including Abeona Therapeutics, Adverum Biotechnologies, Astellas, AVROBIO, Axovant Sciences, Biogen, bluebird bio, BioMarin Pharmaceutical, Homology Medicines, 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.

As of December 31, 2020, we had sixty-two full and part-time employees.

As of December 31, 2021, we had 102 full and part-time employees.

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

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

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

UAB is the clinical trial site for the Phase 1 trial of Nationwide’s C134 oncolytic virus (MB-108).

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

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 C134 oncolytic virus (MB-108).

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

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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In August 2019, the FDA approved our IND application to initiate a multi-center Phase 1/2 clinical trial of MB-102 (CD123 CAR T) and in January 2021, the FDA approved our IND application to initiate a multi-center Phase 2 clinical trial of MB-107 (XSCID).

In May 2021, the FDA approved our IND application to initiate a multi-center Phase 1/2 clinical trial of MB-106 (CD-20).

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.

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Numerous governmental authorities, principally the FDA and corresponding state and foreign regulatory agencies, impose substantial regulations upon the clinical development, manufacture and marketing of our product candidates, as well as our ongoing research and development activities.

None of our product candidates has been approved for sale in any market in which we have marketing rights.

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 Food, Drug and Cosmetic Act (“FDCA”).

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Our submission of an IND may not result in FDA authorization to commence a clinical trial.

The FDA may permit expedited development, evaluation, and marketing of new therapies intended to treat persons with serious or life-threatening conditions for which there is an unmet medical need under its fast track drug development programs.

A sponsor can apply for fast track designation at the time of submission of an IND, or at any time prior to receiving marketing approval of the new drug application (“NDA”) or biologics license application (“BLA”).

A sponsor can apply for fast track designation initially at the time of submission of an IND, or at any time prior to receiving a marketing approval of the new drug application (“NDA”) or biologics license application (“BLA”).

To receive fast track designation, an applicant must demonstrate:

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Sponsors of products in fast track drug development programs must be in regular contact with the reviewing division of the FDA to ensure that the evidence necessary to support marketing approval will be developed and presented in a format conducive to an efficient review.

Sponsors of products in fast track drug development programs ordinarily are eligible for priority review of a completed application in six months or less and also may be permitted to submit portions of an NDA or BLA to the FDA for review before the complete application is submitted.

In accordance with the FDCA, sponsors of drugs for serious or life-threatening diseases that fill an unmet medical need may seek approval under the FDA’s accelerated approval regulations.

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Approval will be subject to the requirement that the applicant study the drug further to verify and describe its clinical benefit where there is uncertainty as to the relation of the surrogate endpoint to clinical benefit or uncertainty as to the relation of the observed clinical benefit to ultimate outcome.

Post-marketing studies are usually underway at the time an applicant files the NDA.

Post-marketing studies are usually underway at the time an applicant files the NDA or BLA.

When required to be conducted, such post-marketing studies must also be adequate and well-controlled.

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Studies establish safety and efficacy in an expanded patient population.

Phase 4 post-marketing studies may be requested by the FDA to find out more about the drug’s long-term risks, benefits, and optimal use, or to test the drug in different patient populations.

The FDA may request phase 4 post-marketing studies to find out more about the drug’s long-term risks, benefits, and optimal use, or to test the drug in different patient populations.

The length of time necessary to complete clinical trials varies significantly and may be difficult to predict.

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● ineffectiveness of the product candidates.

In addition, the FDA, equivalent foreign regulatory authority, or a data safety monitoring committee for a trial may place a clinical trial on hold or terminate it if it concludes that subjects are being exposed to an unacceptable health risk, or for futility.

In addition, the FDA, equivalent foreign regulatory authority, or a data safety monitoring committee for a clinical trial may place a clinical trial on hold or terminate it if it concludes that subjects are being exposed to an unacceptable health risk, or for futility.

Any drug is likely to produce some toxicity or undesirable side effects in animals and in humans when administered at sufficiently high doses and/or for a sufficiently long period of time.

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The SPA process is a procedure by which the FDA provides official evaluation and written guidance on the design and size of proposed protocols that are intended to form the basis for an NDA or BLA.

However, final marketing approval depends on the results of efficacy, the adverse event profile and an evaluation of the benefit/risk of treatment demonstrated in the pivotal 3 trial.

The SPA may only be changed through a written agreement between the sponsor and the FDA, or in rare cases if the FDA becomes aware of a substantial scientific issue essential to product safety or efficacy the SPA can be rescinded.

However, final marketing approval depends on the results of efficacy, the adverse event profile and an evaluation of the benefit/risk of treatment demonstrated in the pivotal clinical trial.

Once approved, the SPA may only be changed through a written agreement between the sponsor and the FDA, or in rare cases if the FDA becomes aware of a substantial scientific issue essential to product safety or efficacy the SPA can be rescinded.

Before receiving FDA approval to market a product, we must demonstrate that the product is safe and effective for its intended use by submitting to the FDA an NDA or BLA containing the preclinical and clinical data that have been accumulated, together with chemistry and manufacturing and controls specifications and information, and proposed labeling, among other things.

1 unchanged sentence

Although uncommon, the FDA may request a Risk Evaluation and Mitigation Strategy, or REMS, as part of an NDA or BLA approval for products with serious safety concerns to help ensure that the benefits of the product outweigh the risks.

The REMS plan contains post-market obligations of the sponsor to train prescribing physicians, monitor off-label drug use, and perhaps the conduct of Phase 4 follow-up studies and registries to ensure the continued safe use of the drug.

The REMS plan contains post-marketing obligations of the sponsor to train prescribing physicians, monitor off-label drug use, and perhaps the conduct of Phase 4 follow-up studies and registries to ensure the continued safe use of the drug.

As part of the approval process, the FDA must inspect and approve each manufacturing facility.

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Drugs whose review was accelerated may carry additional restrictions on marketing activities, including the requirement that all promotional materials are pre-submitted to the FDA.

Claims exceeding those contained in approved labeling will constitute a violation of the FDCA.

Claims exceeding those contained in the approved labeling will constitute a violation of the FDCA.

Violations of the FDCA or regulatory requirements at any time during the product development process, approval process, or marketing and sale following approval may result in agency enforcement actions, including withdrawal of approval, recall, seizure of products, warning letters, injunctions, fines and/or civil or criminal penalties.

11 unchanged sentences

International Regulation

In addition to regulations in the U.S., there are a variety of foreign regulations governing clinical trials and commercial sales and distribution of any product candidates.

In addition to regulations in the U.S., there are a variety of foreign regulations governing clinical trials and commercial sales and distribution of our product candidates.

The approval process varies from country to country, and the time may be longer or shorter than that required for FDA approval.

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