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Item 1. Business

2022-03-28 compared with 2021-03-31 · 126 added, 80 removed, 385 unchanged (35% of the section changed)

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Fortress has a talented and experienced business development team, comprising scientists, doctors and finance professionals, who identify and evaluate promising products and product candidates for potential acquisition by new or existing partner companies.

Through our partner companies, we have executed arrangements with some of the world’s foremost universities, research institutes and pharmaceutical companies, including Fred Hutchinson Cancer Research Center, St.

Jude Children’s Research Hospital, Dana-Farber Cancer Institute, Nationwide Children’s Hospital, Cincinnati Children’s Hospital Medical Center, Columbia University, the University of Pennsylvania, AstraZeneca plc, and City of Hope National Medical Center.

Through our partner companies, we have executed arrangements with some of the world’s foremost universities, research institutes and pharmaceutical companies, including City of Hope National Medical Center, Fred Hutchinson Cancer Research Center, St.

Jude Children’s Research Hospital, Dana-Farber Cancer Institute, Nationwide Children’s Hospital, Cincinnati Children’s Hospital Medical Center, Columbia University, the University of Pennsylvania, Mayo Foundation for Medical Education and Research, AstraZeneca plc, and Dr.

Reddy’s Laboratories, Ltd.

Following the exclusive license or other acquisition of the intellectual property underpinning a product or product candidate, Fortress leverages its business, scientific, regulatory, legal and finance expertise to help the partners achieve their goals.

Partner companies assess a broad range of strategic arrangements to accelerate and provide additional funding to support research and development, including joint ventures, partnerships, out-licensings, and public and private financings.

To date, three partner companies are publicly traded, and three have consummated strategic partnerships with industry leaders Alexion Pharmaceuticals, Inc., Sentynl Therapeutics, Inc., and InvaGen Pharmaceuticals, Inc.

(a subsidiary of Cipla Limited).

Several of our partner companies possess licenses to product candidate intellectual property, including Aevitas Therapeutics, Inc.

(“Aevitas”), Avenue Therapeutics, Inc.

(“Avenue”), Baergic Bio, Inc.

To date, four partner companies are publicly traded, and two have consummated strategic partnerships with industry leaders AstraZeneca plc (as successor-in-interest to Alexion Pharmaceuticals, Inc.) and Sentynl Therapeutics, Inc.

Our subsidiary and partner companies that are pursuing development and/or commercialization of biopharmaceutical products and product candidates include Aevitas Therapeutics, Inc.

(“Aevitas”), Baergic Bio, Inc.

(“Baergic”), Caelum Biosciences, Inc.

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(“Helocyte”), Journey Medical Corporation (“Journey” or “JMC”), Mustang Bio, Inc.

(“Mustang”) and Oncogenuity, Inc.

(“Oncogenuity”).

(“Mustang”), Oncogenuity, Inc.

(“Oncogenuity”) and UR-1 Therapeutics, Inc.

The Company is a Delaware corporation incorporated in 2006.

As used throughout this filing, the words “we”, “us” and “our” may refer to Fortress individually or together with our affiliates and partners, as dictated by context.

As used throughout this filing, the words “we”, “us” and “our” may refer to Fortress individually or together with our affiliates and partners, and the word “partner” refers to either entities that are publicy traded and in which we own or control a majority of the ownership position or third party entities with whom we have a significant business relationship, each as dictated by context.

We refer to private companies in which we own or control a majority of the ownership position as our subsidiaries;

however instances of either term should be read as applying to either or both as dictated by context.

Product Candidates and Other Intellectual Property

Commercialized Products

Through our partner company Journey we market the following dermatology products:

Through our partner company Journey we actively market the following branded dermatology products:

Qbrexza is a medicated cloth towelette for the treatment of primary axillary hyperhidrosis.

Accutane (isotretinoin) capsule is an oral retinoid indicated for the treatment of severe recalcitrant nodular acne.

Ximino (minocycline hydrochloride) extended release capsule is a tetracycline-class drug indicated to treat only inflammatory lesions of non-nodular moderate to severe acne vulgaris.

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Exelderm (sulconazole nitrate, USP) Cream and Solution are antifungal agents indicated for the treatment of tinea infection, such as ringworm and jock itch.

Ceracade Skin Emulsion is a steroid-free, ceramide-dominant formulation used to treat dry skin conditions and to manage and relieve the burning and itching associated with various types of dermatitis and radiation dermatitis.

Luxamend Wound Cream is a water-based emulsion formulated for the dressing and management of superficial wounds, minor abrasions, dermal ulcers, donor sites, first- and second-degree burns, including sunburns, and radiation dermatitis.

Accutane (isotretinoin) capsules is an oral retinoid indicated for the treatment of severe recalcitrant nodular acne.

Amzeeq is a minocycline topical foam, 4% for the treatment of inflammatory lesions of non-nodular moderate to severe acne vulgaris in adults and children 9 years and older.

Zilxi is a minocycline topical foam, 1.5% is the first and only topical minocycline treatment for inflammatory lesions due to rosacea in adults.

Anti-itch product:

non-steriodal and antihistamine free topical steroid for the treatment of pruiritis, scabies and other skin itch conditions to be launched in the second quarter of 2022.

Late Stage Product Candidates

Intravenous (IV) Tramadol

Our partner company Avenue, in collaboration with InvaGen Pharmaceuticals, Inc., is developing intravenous (“IV”) Tramadol, for the treatment of post-operative acute pain.

IV Tramadol may fill a gap in the acute pain market between IV acetaminophen/NSAIDs and conventional IV narcotics.

Avenue announced in May 2018 that its first pivotal Phase 3 study had met its primary endpoint and all key secondary endpoints.

In June 2019, Avenue announced that its second pivotal Phase 3 study had met its primary endpoint and all key secondary endpoints.

In December 2019, Avenue submitted a new drug application (“NDA”), for IV Tramadol to treat moderate to moderately severe postoperative pain pursuant to Section 505(b)(2) of the Federal Food, Drug and Cosmetic Act (“FDCA”).

On October 12, 2020, Avenue announced that it had received a Complete Response Letter (“CRL”) from the U.S.

Food and Drug Administration (“FDA”) regarding Avenue’s NDA for IV Tramadol.

In November 2020, Avenue attended a Type A Meeting with the FDA to discuss issues raised in the CRL.

On February 12, 2021 Avenue resubmitted its NDA to the FDA for IV Tramadol.

The NDA resubmission follows the receipt of official minutes from a Type A meeting with the FDA, which was conducted following receipt of Avenue’s CRL.

The NDA resubmission included revised language relating to the proposed product label and a report relating to terminal sterilization validation.

On February 26, 2021, Avenue received an acknowledgement letter from the FDA that Avenue’s resubmission of its NDA is a complete, class 1 response to the CRL, and a Prescription Drug User Fee Act goal date has been set for April 12, 2021.

CUTX-101 (Copper Histidinate injection for Menkes Disease)

Our partner company Cyprium is currently developing CUTX-101, a copper histidinate injection for the treatment of Menkes disease.

Menkes disease is a rare X-linked pediatric disease caused by gene mutations of copper transporter ATP7A, which affects approximately 1 in 34,810 live male births, and potentially as high as 1 in 8,664 live male births, based on recent genome-based ascertainment study.

Menkes disease is characterized by distinctive clinical features, including sparse and depigmented hair (“kinky hair”), failure to thrive, connective tissue disorders and severe neurological symptoms such as seizures and hypotonia.

Biochemically, Menkes patients may have low serum copper levels, as well as abnormal levels of catecholamine, but definitive diagnosis is typically made by sequencing of the ATP7A gene.

There is no current FDA-approved treatment for Menkes disease.

There is no current U.S.

Food and Drug Administration (“FDA”) - approved treatment for Menkes disease.

CUTX-101, along with an AAV-ATP7A gene therapy that is also being developed by Cyprium, was granted Orphan Drug Designation by the FDA.

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Additional information on the Expanded Access study can be found on www.ClinicalTrials.gov using identifier NCT04074512.

Cyprium intends to begin the rolling submission of a NDA to the FDA for CUTX-101 in the second half of 2021.

The information contained on this website is not included in, or incorporated by reference into, this Annual Report on Form 10-K.

On February 24, 2021, Cyprium announced the execution of an asset purchase agreement with Sentynl Therapeutics, Inc.

(“Sentynl”), a U.S.-based specialty pharmaceutical company owned by the Zydus Group.

The asset purchase agreement commits Sentynl to an upfront cash payment to Cyprium of $8.0 million, which was paid upon execution of the agreement, and $12.0 million in future development and regulatory cash milestones through NDA approval, as well as potential sales milestones.

The asset purchase agreement commits Sentynl to an upfront cash payment to Cyprium of $8.0 million, which was paid upon execution of the agreement, and $12.0 million in future development and regulatory cash milestones through New Drug Application (“NDA”) approval, as well as potential sales milestones.

Royalties on CUTX-101 net sales ranging from the mid-single digits up to the mid-twenties are also payable.

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Cyprium will retain 100% ownership over any FDA priority review voucher that may be issued at NDA approval for CUTX-101.

In October 2021, Cyprium announced positive results from an efficacy and safety analysis of data integrated from two completed pivotal studies in patients with Menkes disease treated with CUTX-101, copper histidinate (CuHis).

These data were presented as a virtual poster at the 2021 American Academy of Pediatrics National Conference & Exhibition.

On December 7, 2021, Cyprium announced the initiation of a rolling submission of its NDA to the FDA for CUTX-101 for the treatment of Menkes disease.

Cyprium expects to complete the submission of the NDA to the FDA in mid-2022.

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

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In May 2020, Mustang submitted an Investigational New Product Drug Application (“IND”) application with the FDA to initiate a registrational multicenter Phase 2 clinical trial of MB-107 in newly diagnosed infants with XSCID who are under the age of two.

In response, the FDA identified CMC hold issues that Mustang satisfactorily addressed in a December 2020 submission to the Agency, and the CMC hold was removed in January 2021.

Potential topline data from the trial are expected in the fourth quarter of 2022.

Mustang expects to file an IND in the second quarter of 2021 for a registrational multicenter Phase 2 clinical trial of MB-207 in previously transplanted XSCID patients.

Potential topline data from this trial are expected in the first half of 2023.

Cosibelimab (Anti-PD-L1 mAb for mCSCC and NSCLC)

Our partner company Checkpoint is currently evaluating its lead antibody product candidate, cosibelimab (formerly CK-301), an anti-PD-L1 antibody licensed from the Dana-Farber Cancer Institute, in a Phase 1 clinical trial in Checkpoint therapy-naïve patients with selected recurrent or metastatic cancers, including ongoing cohorts intended to support one or more Biologics License Application (“BLA”) submissions.

In response, the FDA identified Chemistry, Manufacturing and Controls (“CMC”) hold issues that Mustang satisfactorily addressed in a December 2020 submission to the Agency, and the CMC hold was removed in January 2021.

Mustang filed an IND in the fourth quarter of 2021 for a pivotal non-randomized multicenter Phase 2 clinical trial of MB-207 in previously transplanted XSCID patients.

In January 2022, the FDA issued a hold, pending CMC clearance, on Mustang’s IND application.

Cosibelimab (Anti-PD-L1 mAb for CSCC and NSCLC)

Our partner company Checkpoint is currently evaluating its lead antibody product candidate, cosibelimab (formerly CK-301), an anti-PD-L1 antibody licensed from the Dana-Farber Cancer Institute, in an ongoing global, open-label, multicohort Phase 1 clinical trial in checkpoint therapy-naïve patients with selected recurrent or metastatic cancers, including ongoing cohorts in locally advanced and metastatic cutaneous squamous cell carcinoma (“CSCC”) intended to support one or more applications for marketing approval.

Additional information on the Phase 1 trial can be found on www.ClinicalTrials.gov using identifier NCT03212404.

Checkpoint also has a collaboration agreement with TG Therapeutics, Inc.

(“TGTX”) whereby TGTX was granted the rights to develop and commercialize cosibelimab in the field of hematological malignancies.

In September 2020, Checkpoint announced interim results from the registration-enabling Phase 1 clinical trial in metastatic cutaneous squamous cell carcinoma (“mCSCC”) at the European Society for Medical Oncology (“ESMO”) Virtual Congress 2020.

Checkpoint expects top-line results from the trial in the second half of 2021.

In November 2020, Checkpoint announced updated results from the ongoing global, open-label, multicohort Phase 1 clinical trial including a cohort of patients with previously untreated high PD-L1 expressing advanced non-small cell lung cancer (“NSCLC”).

CK-101 (EGFR inhibitor for EGFR mutation-positive NSCLC)

Checkpoint is also currently evaluating a lead small-molecule, targeted anti-cancer agent, CK-101, in a Phase 1 clinical trial for the treatment of patients with EGFR mutation-positive NSCLC.

(“TGTX”) whereby TGTX was granted the rights to develop and commercialize cosibelimab in the field of hematological malignancies, while Checkpoint retains the right to develop and commercialize these assets in solid tumors.

In December 2021, Checkpoint announced the initiation of the CONTERNO study, a global, open-label, multi-center, randomized Phase 3 trial of cosibelimab in combination with pemetrexed and platinum chemotherapy for the first-line treatment of patients with non-squamous non-small cell lung cancer (“NSCLC”).

The primary endpoint for the CONTERNO Phase 3 trial is overall survival (“OS”), and key secondary endpoints include progression-free survival (“PFS”), objective response rate (“ORR”), and safety.

The study is designed to potentially support full regulatory approvals worldwide.

In January 2022, Checkpoint announced positive topline results from a cohort of the registration-enabling Phase 1 clinical trial of cosibelimab administered as a fixed dose of 800 mg every two weeks in patients with metastatic CSCC.

The cohort met its primary endpoint, with cosibelimab demonstrating a confirmed ORR of 47.4% (95% CI:

36.0, 59.1) based on independent central review of 78 patients enrolled in the metastatic CSCC cohort using Response Evaluation Criteria in Solid Tumors version 1.1 (“RECIST 1.1”).

Based on these results, Checkpoint intends to submit a Biologics License Application (“BLA”) to the U.S.

Food and Drug Administration (“FDA”) for cosibelimab in late 2022, to be followed by a marketing authorization application (“MAA”) submission in Europe and additional potential submissions in markets worldwide.

Olafertinib (also known as CK-101, EGFR inhibitor for EGFR mutation-positive NSCLC)

Checkpoint is also currently evaluating a lead small-molecule, targeted anti-cancer agent, olafertinib as an oral, third-generation, irreversible kinase inhibitor against selective mutations of epidermal growth factor receptors (“EGFR”) in a Phase 1 clinical trial for the potential treatment of adult patients with metastatic NSCLC, whose tumors have EGFR exon 19 deletion mutations.

Checkpoint believes that olafertinib has the potential to be effective in this population as a monotherapy or in combination with other anti-tumor immune response potentiating compounds.

In September 2017, Checkpoint received FDA Orphan Drug Designation for olafertinib for the treatment of EGFR mutation-positive NSCLC.

In September 2018, Checkpoint announced preliminary interim safety and efficacy data from the ongoing Phase 1 clinical trial.

The data were presented in an oral presentation at the International Association for the Study of Lung Cancer (“IASLC”) 19th World Conference on Lung Cancer in Toronto.

The clinical trial is ongoing to identify the optimal dose to maximize therapeutic effect, following which a Phase 3 trial is planned in treatment-naïve EGFR mutation-positive NSCLC patients.

Additional information on the Phase 1 trial can be found on www.ClinicalTrials.gov using identifier NCT02926768.

In November 2020, NeuPharma, Inc.

commenced a Phase 3 clinical trial in China evaluating CK-101 in treatment-naïve locally advanced or metastatic NSCLC patients whose tumors have EGFR exon 19 deletion mutations.

We intend to meet with the FDA to discuss the adequacy of the ongoing Phase 3 trial in China.

CAEL-101 (mAb for AL Amyloidosis)

Our partner company Caelum, in collaboration with Alexion Pharmaceuticals, Inc.

(“Alexion”), is working to develop a novel, first-in-class monoclonal antibody called CAEL-101 for the treatment of amyloid light chain (“AL”) amyloidosis.

commenced a Phase 3 clinical trial in China evaluating olafertinib in treatment-naïve locally advanced or metastatic NSCLC patients whose tumors have EGFR exon 19 deletion mutations.

Checkpoint has met with the FDA to discuss the adequacy of the ongoing Phase 3 trial in China.

CAEL-101 ( Light Chain Fibril-reactive Monoclonal Antibody for AL Amyloidosis)

Our former partner company Caelum, in collaboration with AstraZeneca plc (“AstraZeneca”), is working to develop a novel, first-in-class monoclonal antibody called CAEL-101 for the treatment of amyloid light chain (“AL”) amyloidosis.

CAEL-101 is designed to improve organ function by reducing or eliminating amyloid deposits in the tissues and organs of patients with AL amyloidosis.

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Additional information on the Phase 3 trials, both of which are actively enrolling patients, can be found at www.ClinicalTrials.gov using identifiers NCT04512235 and NCT04504825.

In December 2020, AstraZeneca (“AZ”) announced its intention to acquire Alexion, with the acquisition expected to close by the third quarter of 2021, as the acquisition is subject to approval by both AZ and Alexion shareholders, as well as certain regulatory approvals, share listing approvals, and other customary closing conditions.

The acquisition of Alexion by AZ triggers the Change of Control clause in the Amended and Restated Development, Option and Stock Purchase Agreement entered into by and among Caelum, Alexion, the Company, and Caelum security holders, such that Alexion’s purchase option expires on the date that is six months after the closing of any Change of Control.

On October 5, 2021, AstraZeneca acquired Caelum for an upfront payment of approximately $150 million paid to Caelum shareholders, of which approximately $56.9 million was paid to Fortress, net of the ten percent, 24-month escrow holdback amount and other miscellaneous transaction expenses.

The agreement also provides for additional potential payments to Caelum shareholders totaling up to $350 million, payable upon the achievement of regulatory and commercial milestones.

Fortress is eligible to receive 42.4% of all possible proceeds of the transaction, totaling up to approximately $212 million.

Triplex (Vaccine for Cytomegalovirus)

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Helocyte secured an exclusive, worldwide license to Triplex from City of Hope National Medical Center (“COH”) in April of 2015.

In December 2021, Helocyte announced that a Phase 2 double-blind, randomized, placebo-controlled clinical trial was initiated to evaluate the safety and efficacy of Triplex, a cytomegalovirus (“CMV”) vaccine, in eliciting a CMV-specific immune response and reducing CMV replication in people living with HIV.

The trial is being conducted by the AIDS Clinical Trials Group and is funded by the National Institute of Allergy and Infectious Disease, part of the National Institutes of Health.

CEVA101 (Cellular Therapeutic for Severe Traumatic Brain Injury)

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In separate Phase 1 trials of adults and children with severe TBI, CEVA101 was observed to be safe, well-tolerated and efficacious (resulting in volumetric preservation versus time-matched controls, and in the case of children, reducing the Pediatric Intensity Level of Therapy or PILOT score), see ClinicalTrials.gov Identifiers NCT01575470 and NCT0254722.

In a recently-completed, randomized, placebo-controlled, multi-center Phase 2 study of children with severe TBI, CEVA101 was similarly observed to be safe, well-tolerated and efficacious (resulting in volumetric preservation and a

reduction in the PILOT score of those receiving CEVA101 versus those receiving placebo), see ClinicalTrials.gov Identifier NCT01851083).

In a randomized, placebo-controlled, multi-center Phase 2 study of children with severe TBI completed in November 2020, CEVA101 was similarly observed to be safe, well-tolerated and efficacious (resulting in volumetric preservation and a reduction in the PILOT score of those receiving CEVA101 versus those receiving placebo), see ClinicalTrials.gov Identifier NCT01851083).

A randomized, placebo-controlled Phase 2 study of CEVA101 for the treatment of severe TBI in adults is ongoing (see ClinicalTrials.gov Identifier NCT02525432).

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Cellvation secured an exclusive worldwide license to CEVA101 (as well as CEVA-D and CEVA102) from University of Texas Health Science Center at Houston in October of 2016.

DFD-29 (A Modified Release Oral Minocycline for Inflammatory Lesions of Rosacea)

Through our partner company Journey in collaboration with Dr.

Reddy’s Laboratories, Ltd.

(“DRL”), we are developing DFD-29, a modified release oral minocycline for the treatment of inflammatory lesions of rosacea.

In connection with the DRL collaboration, Journey will complete the development of DFD-29, which includes conducting two Phase 3 studies to assess the efficacy, safety and tolerability of oral DFD-29 for the treatment of rosacea and the regulatory submission of a new drug application under Section 505(b)(2) of the FDCA.

In addition, DRL will provide development support including the monitoring of two Phase 3 clinical trials.

Journey is planning on initiating the Phase 3 trials in the first quarter of 2022 with top-line data expected in the second half of 2022 and an anticipated NDA filing in the second half of 2023.

Journey dosed the first patient in the Phase 3 program in March 2022.

Early Stage Product Candidates

MB-102 (CD123 CAR T for BPDCN)

Through our partner company UR-1, in May 2021, we acquired an exclusive license from Fuji Yakuhin Co.

(“Fuji”) to develop Dotinurad in North America and Europe.

Dotinurad is a potential best-in-class urate transporter (URAT1) inhibitor for gout and possibly other hyperuricemic indications.

Dotinurad (URECE® tablet) was approved in Japan in 2020 as a once-daily oral therapy for gout and hyperuricemia.

Dotinurad was efficacious and well-tolerated in more than 500 Japanese patients treated for up to 58 weeks in Phase 3 clinical trials.

In December 2021, UR-1 filed an IND with the FDA.

UR-1 expects to initiate a Phase 1 clinical trial to evaluate Dotinurad for the treatment of gout in the first half of 2022.

MB-102 (CD123 CAR T Cell Program for BPDCN, AML and high-risk MDS)

Our partner company Mustang collaborates with COH and Fred Hutchinson Cancer Research Center (“Fred Hutch”) in the development of proprietary, autologous, chimeric antigen receptor (“CAR”) engineered T-cell (“CAR T”) therapies.

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We believe that harnessing the body’s own immune system to treat cancer is the next generation of cancer care that may prove curative across tumor types that have proved resistant to standard pharmacological and biological treatments.

One such CAR T is CD123 or MB-102, a subunit of the heterodimeric interleukin-3-receptor (“IL-3R”), which is widely expressed on human hematologic malignancies, including acute myeloid leukemia (“AML”).

In addition, CD123 can be found on the surface of B cell acute lymphoblastic leukemia, hairy cell leukemia, blastic plasmacytoid dendritic cell neoplasm (“BPDCN”), myelodysplastic syndrome (“MDS”), chronic myeloid leukemia and Hodgkin lymphoma.

Mustang is currently investigating MB-102 as a target for adoptive cellular immunotherapy in BPDCN, since high CD123 expression is associated with enhanced malignant cell proliferation, increased resistance of these cells to apoptosis, and poor clinical prognosis.

Depending on the early results in this patient population, Mustang may broaden the inclusion criteria to include AML and high-risk MDS.

CD123 is overexpressed in the vast majority of cases of AML and high-risk MDS and in essentially all cases of BPDCN.

One such CAR T is CD123 or MB-102, a subunit of the heterodimeric interleukin-3-receptor (“IL-3R”), which is widely expressed on human hematologic malignancies including blastic plasmacytoid dendritic cell neoplasm (“BPDCN”) and acute myeloid leukemia (“AML”).

In addition, CD123 can be found on the surface of B cell acute lymphoblastic leukemia (“B-ALL”), hairy cell leukemia, myelodysplastic syndrome (“MDS”), chronic myeloid leukemia (“CML”) and Hodgkin lymphoma.

Of these malignancies, Mustang is currently investigating CD123 as a target for adoptive cellular immunotherapy in BPDCN, since high CD123 expression is associated with enhanced cell proliferation, increased resistance of these cells to apoptosis, and poor clinical prognosis.

Depending on the early results in this patient population, Mustang may broaden the inclusion criteria to include AML and high-risk MDS (“hrMDS”).

CD123 is overexpressed in the vast majority of cases of AML and hrMDS and in essentially all cases of BPDCN.

In October 2020, Mustang announced the dosing of the first patient in a multicenter Phase 1/2 clinical trial of MB-102 in patients with relapsed or refractory BPDCN ( Clinicaltrials.gov Identifier:

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This is also the first clinical trial under a Mustang IND in which a patient was dosed with cells processed in Mustang’s own manufacturing facility.

MB-101 (IL13R α 2 CAR T for Glioblastoma)

MB-101 (IL13R α 2 CAR T Cell Program for Glioblastoma)

Mustang is also currently developing MB-101, an optimized CAR T product incorporating enhancements in CAR T design and T cell engineering to improve antitumor potency and T cell persistence.

Having optimized dose, schedule, route of administration and T cell selection, a Phase 1 trial is currently underway at COH combining MB-101 with immune checkpoint inhibitors to treat patients with recurrent or refractory glioblastoma multiforme (“GBM”).

Having optimized dose, schedule, route of administration and T cell selection, enrollment in a Phase 1 trial is nearly complete at COH combining MB-101 with immune checkpoint inhibitors to treat patients with recurrent or refractory glioblastoma multiforme (“GBM”).

Additional information on the trial can be found on www.ClinicalTrials.gov using identifier NCT02208362.

In December 2020, Mustang and COH announced the initiation of a Phase 1 trial of MB-101 to treat patients with leptomeningeal brain tumors (e.g.

glioblastoma, ependymoma, or medulloblastoma) and additional information on the trial can be found on www.clinicaltrials.gov using identifier NCT04661384.

In 2021, Mustang expects to initiate a trial of MB-101 in combination with MB-108, an oncolytic virus in-licensed from Nationwide Children’s Hospital, with the goal of potentially enhancing efficacy in treating GBM.

Results form this study has laid the foundation for 3 new MB-101 studies:

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

ClinicalTrials.gov Identifier:

NCT04003649);

MB-101 in treating patients with recurrent or refractory glioblastoma with a substantial component of leptomeningeal disease (currently enrolling patients;

ClinicalTrials.gov Identifier:

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 second half of 2022).

This combination will be referred to as MB-109.

GBM is the most common brain and central nervous system (“CNS”) cancer, accounting for 45.2% of malignant primary brain and CNS tumors, 54% of all gliomas, and 16% of all primary brain and CNS tumors.

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While GBM is a rare disease (2-3 cases per 100,000 persons per year in the US and EU), it is quite lethal, with five-year survival rates historically under 10%.

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.

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.

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

MB-106 (CD20 CAR T for B-cell non-Hodgkin lymphoma)

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

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 non-Hodgkin lymphoma (“NHL”).

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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.

A CD20-targeted third-generation autologous CAR T cell therapy is being developed by our partner company Mustang in a collaboration with the Fred Hutchinson Cancer Research Center (“Fred Hutch”).

A CD20-targeted third-generation autologous CAR T cell therapy is being developed by our partner company Mustang in a collaboration with Fred Hutch.

More than 70,000 new cases of NHL are diagnosed each year in the United States, and more than 19,000 patients die of this group of diseases annually.

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The overall response rate was 89% (8/9), and the complete response rate was 44% (4/9).

One patient experienced a grade 1 episode of cytokine release syndrome, and no patients experienced immune effector cell-associated neurotoxicity syndrome.

One patient experienced a grade 1 episode of cytokine release syndrome (“CRS”), and no patients experienced immune effector cell-associated neurotoxicity syndrome (“ICANS”).

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

In May 2021, Mustang announced that the FDA approved its IND application to initiate a multicenter Phase 1/2 clinical trial investigating the safety and efficacy of MB-106.

In June 2021, Mustang announced that MB-106 CD20-targeted CAR T data were presented at EHA2021.

Mazyar Shadman of Fred Hutch presented updated interim data from the ongoing Phase 1/2 clinical trial for B-NHL and CLL, which showed a favorable safety profile and compelling clinical activity, with a 93% overall response rate and 67% complete response rate in patients treated with the modified cell manufacturing process.

In November 2021, Mustang was awarded a grant of approximately $2 million from NCI of the National Institutes of Health.

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

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

Mazyar Shadman of Fred Hutchinson Cancer Research Center presented 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.

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

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Additional information on the ongoing Phase 1 trial of MB-108 can be found on www.ClinicalTrials.gov using identifier NCT03657576.

In 2021 Mustang intends to combine MB-108 with MB-101 to potentially enhance efficacy in treating GBM.

In October 2020 the Phase 1 trial of MB-108 was put on hold 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.

In the second half of 2022 Mustang intends to file an IND for a two-center trial of MB-108 in combination with MB-101 to potentially enhance efficacy in treating GBM.

This combination is to be referred to as MB-109.

In October 2020 the Phase 1 trial of MB-108 was put on hold due to toxicity at the highest dose level;

following dose reduction, no further dose-limiting toxicities have been observed.

MB-105 (PSCA CAR T for Prostate & Pancreatic Cancers)

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In a presentation at the Annual Prostate Cancer Foundation Scientific Retreat, the COH principal investigator reported results from a highly refractory patient treated with MB-105 who experienced a 94 percent reduction in prostate-specific antigen (PSA), near complete reduction of measurable soft tissue metastasis by computerized tomography, and improvement in bone metastases by magnetic resonance imaging.

Mustang believes additional data could potentially be provided in the second half of 2021.

Data presented in February 2022 indicate that PSCA-CAR T-cell therapy is feasible in patients with mCRPC with a dose-limiting toxicity of cystitis, and shows preliminary anti-tumor effect at a dose of 100M cells plus lymphodepletion.

It was concluded that escalation up to the next dose level of 300M can proceed in the trial.

Additional data could protentially be provided in the second half of 2022.

BAER-101 (novel α2/3–subtype-selective GABA A positive allosteric modulator (“PAM”))

Through our majority-owned partner Baergic, we are developing BAER-101, a high affinity, selective modulator of the gamma-aminobutyric acid (“GABA”) A, which is a receptor system with differential binding and modulatory properties dependent on the particular GABA A subtype.

Baergic will explore BAER-101 in a number of CNS disorders where patients are not adequately treated.

Baergic intends to explore BAER-101 in a number of CNS disorders where patients are not adequately treated.

Preclinical Product Candidates

Mayo Clinic CAR T Technology

In August 2021, our partner company Mustang announced an exclusive license agreement with Mayo Foundation for Medical Education and Research (“Mayo Clinic”) for a novel technology to create in vivo CAR T cells that may be able to transform the administration of CAR T therapies and has the potential to be used as an off-the-shelf therapy.

AAV-ATP7A Gene Therapy

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Checkpoint plans to develop CK-103 for the treatment of various advanced and metastatic solid tumor cancers, including, but not limited to, those associated with elevated c-Myc expression.

Checkpoint entered into a collaboration with TGTX to develop CK-103 in the field of hematological malignancies.

Checkpoint entered into an exclusive license agreement with Jubilant Biosys Limited to develop and commercialize novel compounds that inhibit BET bromodomains on a worldwide basis.

Checkpoint entered into a Sublicense Agreement with TGTX to develop and commercialize CK-103 in the field of hematological malignancies.

Checkpoint retains the right to develop and commercialize CK-103 in solid tumors.

Currently, Checkpoint has completed the required CMC, pharmacology and toxicology activities that we believe will support an IND application filing.

CEVA-D and CEVA-102

In partnership with Cellvation, we are developing CEVA-D, a novel bioreactor device that enhances the anti-inflammatory potency of bone marrow-derived cells without genetic manipulation, using wall shear stress (“WSS”) to suppress tumor necrosis factor-a (“TNF-a”) production by activated immune cells.

CEVA-102 is the first cell product produced by CEVA-D, which we plan to develop for various indications, including the treatment of severe traumatic brain injury (“TBI”) in adults and children.

CEVA-102 is the first cell product produced by CEVA-D, which we plan to develop for various indications, including the treatment of severe TBI in adults and children.

CK-302 (Anti-GITR)

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GITR is a co-stimulatory molecule of the TNF receptor family and is expressed on activated T cells, B cells, natural killer (“NK”) and regulatory T cells (“Treg”).

Checkpoint is developing CK-302 for oncology indications where scientific literature supports the potential for an anti-GITR to be effective.

Checkpoint believes that an anti-GITR antibody has the potential to be effective in one or more oncological indications as a monotherapy or in combination with an anti-PD-L1 antibody as well as other anti-tumor immune response potentiating compounds and targeted therapies.

CK-303 (Anti-CAIX)

1 unchanged sentence

Scientific literature indicates that CAIX is a well characterized tumor associated antigen with expression almost exclusively limited to the cells of renal cell carcinoma (“RCC”).

Checkpoint is developing CK-303 for the treatment of patients with RCC in combination with an anti-PD-L1 and/or anti-GITR antibody as well as potentially other anti-tumor immune response potentiating compounds and/or targeted therapies.

More than 85% of RCC cases have been demonstrated to express high levels of CAIX expression.

There is very limited expression of this antigen on healthy tissue which Checkpoint believes will limit reactivity of this antibody against healthy tissues.

Checkpoint is still in preclinical development for this program.

ConVax (formerly Pentamer)

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As of December 31, 2021, we had 173 full-time employees at Fortress and our partner companies.

Journey relies on professional employer organizations and staffing organizations for the employment of its field sales force, which totaled 70 at December 31, 2021.

Executive Officers of Fortress

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ATXI), Checkpoint Therapeutics, Inc.

CKPT), and Mustang Bio, Inc.

CKPT), Mustang Bio, Inc.

MBIO) and Journey Medical Corporation (Nasdaq:

From 1991 to 2008, Dr.

6 unchanged sentences

Prior to serving as the Company’s CFO, Ms.

Hunter served as the Company’s Vice President and Corporate Controller from June 2011 until June 2017, where she implemented financial and operational processes, procedures and policies to facilitate the Company’s execution of its growth strategy.

Hunter served as the Company’s Vice President and Corporate Controller from June 2011 until June 2017, in which capacity she implemented financial and operational processes, procedures and policies to facilitate the Company’s execution of its growth strategy.

From January 2006 to May 2011, Ms.

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Hunter held several positions from Accounting Manager to Vice President and Treasurer of The Stackpole Corporation.

Effective January 2022, Ms.

Hunter currently serves as a member of the board of directors and chairs the audit committee of Tenax Therapeutics, Inc.

Hunter holds a Bachelor of Arts degree in Economics from Union College in Schenectady New York.

36 unchanged sentences

Copies of our and certain of our affiliates’ reports on Form 10-K, Forms 10-Q and Forms 8-K may be obtained, free of charge, electronically through our website at www.fortressbiotech.com.

Our website also includes announcements of investor conferences and events, information on our business strategies and results, corporate governance information, and other news and announcements that investors might find useful or interesting.

The information contained on our website is not included in, or incorporated by reference into, this Annual Report on Form 10-K.

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