What changed in this filing

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Item 1. Business

2025-03-31 compared with 2024-03-28 · 221 added, 271 removed, 373 unchanged (57% of the section changed)

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Fortress works in concert with our extensive network of key opinion leaders to identify and evaluate promising products and product candidates for potential acquisition.

We have executed arrangements in partnership with some of the world’s foremost universities, research institutes and pharmaceutical companies, including City of Hope National Medical Center (“COH” or “City of Hope”), Fred Hutchinson Cancer Center, St.

Jude Children’s Research Hospital (“St.

Jude”), 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 (“Mayo Clinic”), AstraZeneca plc, and Dr.

We have executed arrangements in partnership with some of the world’s foremost universities, research institutes and pharmaceutical companies, including City of Hope National Medical Center, Fred Hutchinson Cancer Center, Dana-Farber Cancer Institute, Nationwide Children’s Hospital, Columbia University, the University of Pennsylvania, 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 financial expertise to help the partners achieve their goals.

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

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.

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

(“AstraZeneca”) and Sentynl Therapeutics, Inc.

(“Sentynl”), respectively.

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

Our subsidiary and partner companies that are pursuing development and/or commercialization of biopharmaceutical products and product candidates are:

Checkpoint Therapeutics, Inc.

CKPT, “Checkpoint”), Journey Medical Corporation (Nasdaq:

DERM, “Journey” or “JMC”), Mustang Bio, Inc.

MBIO, “Mustang”), Avenue Therapeutics, Inc.

ATXI, “Avenue”), Baergic Bio, Inc.

(“Baergic,” a subsidiary of Avenue), Cellvation, Inc.

(“Cellvation”), Checkpoint Therapeutics, Inc.

CKPT, “Checkpoint”), Cyprium Therapeutics, Inc.

(“Cellvation”), Cyprium Therapeutics, Inc.

(“Cyprium”), Helocyte, Inc.

(“Helocyte”), Journey Medical Corporation (Nasdaq:

DERM, “Journey” or “JMC”), Mustang Bio, Inc.

MBIO, “Mustang”), Oncogenuity, Inc.

(“Helocyte”), Oncogenuity, Inc.

(“Oncogenuity”) and Urica Therapeutics, Inc.

Aevitas Therapeutics, Inc.

(“Aevitas”) was a consolidated subsidiary company until the sale of its primary asset to 4D Molecular Therapeutics in April 2023.

As used throughout this filing, the words “we”, “us” and “our” may refer to Fortress individually, to one or more of its subsidiaries and/or partner companies, or to all such entities as a group, as dictated by context.

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The context in which any such term is used throughout this document, however, may dictate a different construal from the foregoing.

Product Candidates and Other Intellectual Property

Revenue Portfolio

Through our partner company Journey we actively market the following branded dermatology products approved by the FDA for sale in the United States:

● Qbrexza® (a medicated cloth towelette for the treatment of primary axillary hyperhidrosis);

● Accutane® (an oral isotretinoin drug for the treatment of severe recalcitrant nodular acne);

● Amzeeq® (minocycline) topical foam, 4% (a topical formulation of minocycline for the treatment of inflammatory lesions of non-nodular moderate to severe acne vulgaris in adults and children nine years and older);

● Zilxi® (minocycline) topical foam, 1.5% (a topical minocycline treatment for inflammatory lesions of rosacea in adults);

● Exelderm® Cream and Solution (a broad-spectrum antifungal intended for topical use);

● Targadox® (an oral doxycycline drug for adjunctive therapy for severe acne);

● Luxamend® (a water-based emulsion formulated to provide an optimally moist healing environment for superficial wounds;

Recent Developments

Checkpoint and UNLOXCYT (cosibelimab-ipdl)

In December 2024, we announced that Checkpoint had received approval for UNLOXCYT, which is the first and only programmed death-ligand 1 (“PD-L1”) blocking antibody to receive U.S.

Food and Drug Administration (“FDA”) marketing approval for the treatment of adults with metastatic cutaneous squamous cell carcinoma (“cSCC”) or locally advanced cSCC who are not candidates for curative surgery or curative radiation.

In March 2025, we announced that Checkpoint entered into an agreement to be acquired by Sun Pharmaceutical Industries, Inc.

(“Sun Pharma”) for $4.10 per share in cash plus a contingent value right of up to $0.70 per share upon the achievement of EU approval.

The closing of the transaction is subject to various conditions including the approval by requisite majorities of holders of Checkpoint’s shares at a meeting of Checkpoint’s stockholders.

We expect the transaction to close in the second quarter of 2025, although there can be no assurance that the transaction closes in a timely manner, or at all.

As of the announcement date, Fortress owned approximately 6.9 million shares of Checkpoint (including Class A Common Stock on an as-converted basis to Common Stock).

Fortress also entered into a royalty agreement with Checkpoint and Sun Pharma pursuant to which Fortress is eligible to receive a royalty of 2.5% on worldwide net sales of UNLOXCYT.

Due to uncertainties as to the timing of the completion of the acquisition, uncertainties as to whether Checkpoint’s

stockholders will vote to approve the transaction, the possibility that competing offers will be made and the possibility that various closing conditions for the transaction may not be satisfied or waived, including that a governmental entity may prohibit, delay or refuse to grant approval for the consummation of the transaction (or only grant approval subject to adverse conditions or limitations), Fortress may not realize the anticipated benefits of the proposed transaction in the time frame expected, or at all.

Journey and EMROSI (Minocycline Hydrochloride Extended-Release Capsules, 40mg)

In November 2024, we announced that partner company Journey received approval of Emrosi (also referred to as DFD-29), a 40mg minocycline hydrochloride extended release capsule for oral use indicated to treat inflammatory lesions (papules and pustules) of rosacea in adults.

Cyprium and CUTX-101 (copper histidinate)

In January 2025, we announced that the FDA had accepted the NDA for CUTX-101, a copper histidinate injection, for priority review for the treatment of Menkes disease.

The Prescription Drug User Fee Act (“PDUFA”) target action date is September 30, 2025 and the candidate has been granted Rare Pediatric Disease Designation by the FDA for the treatment of Menkes disease, Fast Track Designation for classic Menkes disease in patients who have not demonstrated significant clinical progression, and Breakthrough Therapy Designation.

Cyprium is eligible to receive up to $129 million in aggregate development and sales milestones from its partner Sentynl Therapeutics, Inc.

(“Sentynl”), as well as royalties on net sales of CUTX-101 as follows:

(i) 3% of annual net sales up to $75 million;

(ii) 8.75% of annual net sales between $75 million and $100 million;

and (iii) 12.5% of annual net sales in excess of $100 million.

Cyprium will retain 100% ownership over any FDA priority review voucher that may be issued if the NDA for CUTX-101 is approved.

Commercial Products and Product Candidates

Commercial and Approved Products

Through our partner company Journey we market the following branded dermatology products approved by the FDA for sale in the United States:

● Emrosi TM (Minocycline Hydrochloride Extended-Release Capsules, 40mg for the treatment of inflammatory lesions of rosacea in adults):

approved by the FDA in November 2024, which launched in March 2025;

a medicated cloth towelette for the treatment of primary axillary hyperhidrosis;

an oral isotretinoin drug for the treatment of severe recalcitrant nodular acne;

● Amzeeq® (minocycline topical foam, 4%):

a topical formulation of minocycline for the treatment of inflammatory lesions of non-nodular moderate to severe acne vulgaris in adults and children nine years and older;

● Zilxi® (minocycline topical foam, 1.5%):

a topical minocycline treatment for inflammatory lesions of rosacea in adults;

● Exelderm® Cream and Solution:

a broad-spectrum antifungal intended for topical use;

an oral doxycycline drug for adjunctive therapy for severe acne;

a water-based emulsion formulated to provide an optimally moist healing environment for superficial wounds;

minor cuts or scrapes;

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and radiation dermatitis.

Additionally, Journey sells two authorized generic products:

● sulconazole nitrate cream and solution, 1% antifungal agents indicated for the treatment of tinea cruris and tinea corporis caused by Trichophyton rubrum , Trichophyton mentagrophytes , Epidermophyton floccosum , and Microsporum canis ,* and for the treatment of tinea versicolor .

*Efficacy for this organism in the organ system was studied in fewer than 10 infections.

EXELDERM ® Cream is also indicated for the treatment of tinea pedis (athlete's foot).

Effectiveness of EXELDERM ® Solution has not been proven in tinea pedis ;

● doxycycline hyclate immediate release 50mg tablets, indicated as adjunctive therapy for severe acne to reduce the development of drug-resistant bacteria as well as to maintain the effectiveness of doxycycline hyclate and other antibacterial drugs .

Late Stage Product Candidates

Cosibelimab (anti-PD-L1 antibody)

Our partner company Checkpoint is currently developing its lead product candidate, cosibelimab, an anti-programmed death-ligand 1 (“anti-PD-L1”) monoclonal antibody licensed from the Dana-Farber Cancer Institute, in solid tumor indications.

In 2017, Checkpoint commenced a Phase 1 clinical trial in checkpoint therapy-naïve patients with selected recurrent or metastatic cancers.

In January 2022, Checkpoint announced top-line results from a cohort of this study with cosibelimab administered as a fixed dose of 800 mg every two weeks in patients with metastatic cutaneous squamous cell carcinoma (“cSCC”).

The cohort met its primary endpoint, with cosibelimab demonstrating a confirmed overall response (“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 RECIST 1.1.

In June 2022, Checkpoint announced interim results from another cohort of this study with cosibelimab administered as a fixed dose of 800 mg every two weeks in patients with locally advanced cSCC that are not candidates for curative surgery or radiation.

Cosibelimab demonstrated a confirmed ORR of 54.8% (95% CI:

EMROSI (Minocycline Hydrochloride Extended-Release Capsules, 40mg)

Journey received approval in November 2024 for Emrosi (also referred to as DFD-29), a 40mg minocycline hydrochloride extended release capsule for oral use indicated to treat inflammatory lesions (papules and pustules) of rosacea in adults.

Emrosi is now the lowest approved oral minocycline hydrochloride dose.

It was developed using Multiple Unit Pellet System technology, which combines Immediate Release (25%) and Extended Release (75%) Minocycline pellets for uniform drug release.

Emrosi has shown superiority to Oracea® and placebo on the co-primary endpoints and all secondary endpoints in two Phase 3 studies, including reduction of total lesion count, as well as reduction in erythema compared to placebo in both studies and was well-tolerated.

The results from the Phase 3 studies were published in JAMA Dermatology in March 2025.

The NDA was filed under Section 505(b)(2) of the Food Drug and Cosmetic Act (“FDCA”) in January 2024 and was approved in November 2024 by the FDA (NDA 219015).

Emrosi has Orange Book-listed patents that extend through January of 2039.

In March 2025, Journey announced the commercial launch of Emrosi.

UNLOXCYT (cosibelimab-ipdl)

Our partner company Checkpoint received approval in December 2024 for UNLOXCYT, which is the first and only programmed death-ligand 1 blocking antibody to receive FDA marketing approval for the treatment of adults with metastatic cSCC or locally advanced cSCC who are not candidates for curative surgery or curative radiation.

UNLOXCYT is a fully human monoclonal antibody of IgG1 subtype that directly binds to PD-L1 and blocks the PD-L1 interaction with the programmed death receptor-1 (“PD-1”) and B7.1 receptors.

The primary mechanism of action is based on the inhibition of the interaction between PD-L1 and its receptors PD-1 and B7.1, which removes the suppressive effects of PD-L1 on anti-tumor CD8+ T-cells to restore the cytotoxic T cell response.

Additionally, UNLOXCYT has been shown to induce antibody-dependent cellular cytotoxicity (“ADCC”) in vitro.

Checkpoint commenced a Phase 1, multi-center clinical study for cosibelimab-ipdl in October 2017 to evaluate the safety and tolerability of ascending doses in checkpoint therapy-naive patients with selected recurrent or metastatic cancers.

Following completion of dose escalation in March 2018, multiple dose expansion cohorts were initiated, including cohorts in locally advanced and metastatic cSCC.

The primary endpoint is objective response rate (“ORR”), and secondary endpoints include duration of response, progression-free survival (“PFS”), and overall survival.

In January 2022, top-line results were announced from a cohort of this study with cosibelimab-ipdl administered as a fixed dose of 800 mg every two weeks in patients with metastatic cSCC.

The cohort met its primary endpoint, with cosibelimab-ipdl 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”).

In June 2022, interim results were announced from another cohort of this study with cosibelimab-ipdl administered as a fixed dose of 800 mg every two weeks in patients with locally advanced cSCC that are not candidates for curative surgery or radiation in which cosibelimab-ipdl demonstrated a confirmed ORR of 54.8% (95% CI:

36.0, 72.7) based on independent central review of 31 patients enrolled in the cohort.

The design of the interim analysis incorporated feedback from the FDA and is intended to potentially support the approval of cosibelimab in this indication.

In July 2023, Checkpoint announced longer-term results for cosibelimab from its pivotal studies in locally advanced and metastatic cSCC.

In July 2023, longer-term results were announced for cosibelimab-ipdl from its pivotal studies in locally advanced and metastatic cSCC.

These results demonstrated a deepening of response over time, resulting in complete response rates of 26% and 13% in locally advanced and metastatic cSCC, respectively.

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Furthermore, responses continue to remain durable over time with the median duration of response not yet reached in either group.

Updated safety data across 247 patients enrolled and treated with cosibelimab in all cohorts of the ongoing study remain consistent with those previously reported.

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

Food and Drug Administration (“FDA”) for cosibelimab in January 2023.

On December 15, 2023, the FDA issued a Complete Response Letter (“CRL”) for the cosibelimab BLA for the treatment of patients with metastatic or locally advanced cSCC who are not candidates for curative surgery or radiation.

The CRL only cited findings that arose during a multi-sponsor inspection of our third-party contract manufacturing organization as approvability issues to address in a resubmission.

The CRL did not state any concerns about the clinical data package, safety, or labeling.

Following resolution of the inspection issues at the third-party contract manufacturing organization raised in the CRL, a resubmission of the BLA is planned in 2024 to support the marketing approval of cosibelimab.

Checkpoint also previously had 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, while Checkpoint retained the right to develop and commercialize these assets in solid tumors.

Effective September 30, 2023, Checkpoint and TGTX agreed to mutually terminate these collaborations, with full rights reverting back to Checkpoint.

DFD-29 (modified release oral minocycline for the treatment 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 being evaluated for the treatment of inflammatory lesions of rosacea.

Under the DRL arrangement, Journey is responsible for the development of DFD-29, which includes conducting two Phase 3 studies to assess the efficacy, safety and tolerability of DFD-29 for the treatment of rosacea and the regulatory submission of a new drug application under Section 505(b)(2) of the FDCA.

DRL provides development support including the monitoring of two Phase 3 clinical trials, which were initiated in the first quarter of 2022, and completed enrollment in January 2023.

In July 2023, Journey announced positive topline data from our two DFD-29 Phase 3 clinical trials for the treatment of papulopustular rosacea.

The Phase 3 clinical trials achieved the co-primary and all secondary endpoints and subjects completed the 16-week treatment and the drug was well-tolerated.

DFD-29 demonstrated statistical superiority over both the standard of care, Oracea® capsules, and placebo for Investigator’s Global Assessment treatment success and the reduction in the total inflammatory lesion count in both studies.

Journey filed a New Drug Application (“NDA”) with the FDA for DFD-29 on January 4, 2024, paying a $4.0 million filing fee, and announced on March 18, 2024 that the FDA accepted the NDA and assigned a Prescription Drug User Fee Act (“PDUFA”) goal date of November 4, 2024.

Updated safety data across 247 patients enrolled and treated with cosibelimab-ipdl in all cohorts of the ongoing study remain consistent with those previously reported.

Based on these results, Checkpoint submitted a Biologics License Application (“BLA”) to the FDA in January 2023.

On December 15, 2023, the FDA issued a complete response letter (“CRL”) citing only findings that arose during a multi-sponsor inspection of Checkpoint’s third-party contract manufacturing organization as approvability issues to address in a resubmission.

In July 2024, Checkpoint announced the completion of a resubmission of the BLA to the FDA to potentially address the approvability issues cited in the CRL.

In December 2024, Checkpoint announced that the FDA granted approval for UNLOXCYT (cosibelimab-ipdl) for the treatment of adults with metastatic cSCC or locally advanced CSCC who are not candidates for curative surgery or curative radiation.

The recommended commercial dosage of UNLOXCYT is 1,200 mg administered as an intravenous infusion over 60 minutes every three weeks.

In January 2025, Checkpoint

submitted a labeling supplement to the FDA to update the UNLOXCYT label to reflect the longer-term data announced in July 2023.

In March 2025, we announced that Checkpoint entered into an agreement to be acquired by Sun Pharma for $4.10 per share in cash plus a contingent value right of up to $0.70 per share upon the achievement of EU approval.

The closing of the transaction is subject to various conditions including the approval by requisite majorities of holders of Checkpoint’s shares at a meeting of Checkpoint’s stockholders.

We expect the transaction to close in the second quarter of 2025, although there can be no assurance that the transaction closes in a timely manner, or at all.

Due to uncertainties as to the timing of the completion of the acquisition, uncertainties as to whether Checkpoint’s stockholders will vote to approve the transaction, the possibility that competing offers will be made and the possibility that various closing conditions for the transaction may not be satisfied or waived, Fortress may not realize the anticipated benefits of the proposed transaction in the time frame expected, or at all.

Late Stage Product Candidates

CUTX-101 (copper histidinate injection for Menkes disease)

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

Our subsidiary Cyprium was previously 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 a recent genome-based ascertainment study.

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Under the Sentynl APA, Sentynl provided certain development funding for the CUTX-101 program, with Cyprium initially remaining in control of development of such program.

Pursuant to a contractual right exercised by Sentynl in October 2023, however, Cyprium assigned the NDA and certain other assets pertaining to the CUTX-101 program to Sentynl and received $4.5 million in connection with the closing of such transaction.

Sentynl is now obligated to use commercially reasonable efforts to develop and commercialize CUTX-101, including the funding of the same.

Pursuant to a contractual right exercised by Sentynl in October 2023, Cyprium assigned the NDA and certain other assets pertaining to the CUTX-101 program to Sentynl and received $4.5 million in connection with the closing of such transaction.

Sentynl is obligated to use commercially reasonable efforts to develop and commercialize CUTX-101, including the funding of the same.

Additionally, Cyprium remains eligible to receive up to $129 million in aggregate development and sales milestones under the Agreement , and royalties on net sales of CUTX-101 as follows:

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and (iii) 12.5% of annual net sales in excess of $100 million.

Cyprium will retain 100% ownership over any FDA priority review voucher that may be issued if

the NDA for CUTX-101 is approved.

The CUTX-101 rolling NDA submission is ongoing and is expected to be completed by Sentynl in 2024.

Cyprium will retain 100% ownership over any FDA priority review voucher that may be issued if the NDA for CUTX-101 is approved.

On January 6, 2025, we announced that the FDA accepted the NDA for CUTX-101 for priority review, and on January 16, 2025, we disclosed the extension of the PDUFA target action date to September 30, 2025.

Cyprium previously enrolled patients into an Intermediate-Size Patient Population Expanded Access Protocol which is now administered by Sentynl Therapeutics.

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

Additional information on the Expanded Access study and requirements can

be found on ClinicalTrials.gov using identifier NCT04074512.

Information on clinicaltrials.gov does not constitute part of this Annual Report on Form 10-K.

Our partner company Avenue is developing an intravenous formulation of tramadol (“IV tramadol”), a schedule IV opioid for the treatment of post-operative acute pain.

Avenue completed two Phase 3 efficacy studies in 2018 and 2019 and announced that both had met their primary endpoints and all key secondary endpoints.

In December 2019, Avenue submitted an 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”), and following a CRL received in October 2020, resubmitted the NDA in February 2021.

The FDA assigned a PDUFA goal date of April 12, 2021 for the resubmitted NDA for IV Tramadol.

On June 14, 2021, we announced that we had received a second CRL.

We submitted a formal dispute resolution request (“FDRR”) with the Office of Neuroscience of the FDA on July 27, 2021.

On August 26, 2021, we received an Appeal Denied Letter from the Office of Neuroscience of the FDA in response to the FDRR submitted on July 27, 2021.

On August 31, 2021, we submitted a FDRR with the Office of New Drugs (“OND”) of the FDA.

On October 21, 2021, we received a written response from the OND of the FDA stating that the OND needs additional input from an Advisory Committee in order to reach a decision on the FDRR.

In February 2022, Avenue held an Advisory Committee meeting with the FDA regarding IV tramadol.

In the final part of the public meeting, the Advisory Committee voted yes or no on the following question:

“Has the Applicant submitted adequate information to support the position that the benefits of their product outweigh the risks for the management of acute pain severe enough to require an opioid analgesic in an inpatient setting?” The results were 8 yes votes and 14 no votes.

In March 2022, Avenue received an Appeal Denied Letter from the Office of New Drugs in response to the formal dispute resolution request.

In August 2022, Avenue participated in a Type A Meeting with the FDA Division of Anesthesia, Analgesia, and Addiction Products (“DAAAP”) regarding a briefing document submitted that presented a study design the Avenue believed would have the potential to address the comments and deficiencies noted in the Letter.

In January 2024, Avenue announced that they reached final agreement with the FDA on the Phase 3 safety study protocol and statistical analysis approach, including the primary endpoint.

The final non-inferiority study is designed to assess the risk of opioid-induced respiratory depression related to opioid stacking on IV tramadol compared to IV morphine.

The study will randomize approximately 300 post bunionectomy patients to IV tramadol or IV morphine for pain relief administered during a 48-hour post-operative period.

Of note, the same surgical model was used in a pivotal Phase 3 Trial.

In the Phase 3 safety study to be conducted, patients will have access to IV hydromorphone, a Schedule II opioid, for rescue of breakthrough pain.

The primary endpoint is a composite of elements indicative of respiratory depression.

Avenue plans to initiate the study as soon as possible, subject to having the necessary financing.

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

Checkpoint is 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”) 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.

Olafertinib has FDA Orphan Drug Designation 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.

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

Triplex (cytomegalovirus (CMV) vaccine)

Through our subsidiary Helocyte, we are developing Triplex, a universal recombinant Modified Vaccinia Ankara viral vector vaccine engineered to induce a rapid, robust and durable virus-specific T cell response to three immuno-dominant proteins (UL83 (pp65), UL123 (IE1), and UL122 (IE2)) linked to cytomegalovirus (“CMV”).

In a Phase 1 study, Triplex was observed to be safe, well-tolerated and highly immunogenic when administered to healthy volunteers at multiple dose levels ( ClinicalTrials.gov Identifier:

NCT01941056).

In a Phase 2 trial, Triplex was observed to be safe, well-tolerated, highly immunogenic and a reduction in CMV events in allogeneic stem cell transplant recipients was observed ( ClinicalTrials.gov Identifier:

NCT02506933).

As of March 2025, Triplex is currently the subject of multiple, ongoing trials in various clinical settings including:

patients undergoing stem cell transplant;

adults co-infected with CMV and Anti-Human Immunodeficiency Virus (“HIV”);

and in combination with a CAR T cell therapy for adults with non-Hodgkin lymphoma (“NHL”) or acute lumphoblastic leukemia (“ALL”).

Helocyte has an exclusive, worldwide license to Triplex from COH.

Information on clinicaltrials.gov does not constitute part of this Annual Report on Form 10-K.

In November 2020, NeuPharma, Inc.

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.

Solid organ transplant

In May 2024, Helocyte announced that the first patient was dosed in a multi-center, placebo-controlled, randomized Phase 2 study of Triplex for control of CMV in patients undergoing liver transplantation.

The trial is funded by a grant from the National Institute of Allergy and Infectious Diseases of the National Institutes of Health that could provide over $20 million in aggregate, non-dilutive funding ( ClinicalTrials.gov Identifier:

NCT06075745 ).

Stem cell transplant

In January 2025, Helocyte announced that the first patient was dosed in a Phase 2 multi-center, placebo-controlled, randomized clinical trial to evaluate Triplex’s effectiveness when administered to human leukocyte antigen (“HLA”) matched related stem cell donors to reduce CMV events in adults undergoing hematopoietic stem cell transplantation (“HSCT”).

The trial is funded by a grant from the National Cancer Institute (“NCI”) (ClinicalTrials.gov Identifier:

NCT06059391).

Helocyte anticipates that its Phase 2 multicenter, double-blind, randomized, placebo-controlled study measuring the safety and effectiveness of Triplex in reducing CMV complications in patients previously infected with CMV and undergoing donor hematopoietic cell transplant to be completed in the second half of 2025 ( ClinicalTrials.gov Identifier:

NCT02506933).

Additionally, Helocyte is recruiting for a Phase 1/2 trial to study side effects and dosage for Triplex in treating pediatric patients with positive cytomegalovirus who are undergoing donor stem cell transplant ( ClinicalTrials.gov Identifier:

NCT03354728).

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 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 ( ClinicalTrials.gov Identifier:

NCT05099965).

Additionally, a trial has been initiated for a Phase 1 trial to evaluate the feasibility and safety of Triplex in combination with a bispecific CMV-HIV CAR for adults living with HIV-1 on stable ART who have maintained viral suppression.

The study is funded by a $11.3 million grant from the California Institute of Regenerative Medicine (CIRM) in addition to other non-dilutive sources ( ClinicalTrials.gov Identifier:

NCT06252402 ).

Helocyte is currently recruiting for two Phase 1 trials in combination with autologous CMV-specific CD19 CAR T cell therapy for adults with intermediate or high grade B-lineage NHL, and in settings following stem cell transplant in patients with high grade B-cell NHL ( ClinicalTrials.gov Identifiers:

NCT05801913 and NCT05432635).

Additionally, a trial has been initiated for a Phase 1 trial in combination with an allogeneic anti-CD19-CAR CMV-specific T cell therapy for patients with high-risk ALL after matched related donor hematopoietic stem cell transplant ( ClinicalTrials.gov Identifier:

NCT06735690).

CAEL-101 (monoclonal antibody for AL amyloidosis)

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The agreement also provides for additional potential payments to Caelum shareholders totaling up to $295 million, payable upon the achievement of regulatory and commercial milestones.

Fortress is eligible to receive 42.4% of all possible proceeds of the transaction, including approximately $148 million to Fortress, with $31.8 million upon BLA approval.

Triplex (cytomegalovirus (CMV) vaccine)

In a Phase 1 study, Triplex was observed to be safe, well-tolerated and highly immunogenic when administered to healthy volunteers at multiple dose levels ( ClinicalTrials.gov Identifier:

NCT01941056).

NCT02506933).

Triplex is currently the subject of four, grant-funded trials in various clinical settings including:

adults undergoing stem cell transplant;

adults co-infected with CMV and Anti-Human Immunodeficiency Virus (“HIV”);

and in combination with a CAR T cell therapy for adults with non-Hodgkin lymphoma (“NHL”).

Helocyte secured an exclusive, worldwide license to Triplex from COH in April 2015.

Helocyte secured an exclusive, worldwide license to Triplex from COH in April of 2015.

Information on clinicaltrials.gov does not constitute part of this Annual Report on Form 10-K.

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.

In August 2022, Helocyte announced that Triplex received a grant from the National Institute of Allergy and Infectious Diseases of the National Institutes of Health that could provide over $20 million in non-dilutive funding.

This competitive award will fund a multi-center, placebo-controlled, randomized Phase 2 study of Triplex for control of CMV in patients undergoing liver transplantation.

The company believes this data set could ultimately be used to support approval of Triplex in this setting and the trial is expected to commence in 2024.

Fortress is eligible to receive 42.4% of all possible potential milestone payments, which together with the upfront payment, would total up to approximately $182 million.

Early and Mid-Stage Product Candidates

Dotinurad (urate transporter (URAT1) inhibitor for gout)

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

(“Fuji”) to develop dotinurad in North America and Europe (with the exclusive licensed territory later expanded to include the Middle East and North Africa).

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.

The clinical program supporting approval included over 1,000 patients.

In June 2023, Urica announced data from the Phase 1 clinical trial in healthy volunteers showed comparable pharmacokinetic, pharmacodynamic and safety profile between U.S.

and Japanese healthy subjects.

In the third quarter of 2023, Urica initiated a Phase 1b clinical trial in patients with gout and hyperuricemia in the U.S.

to compare U.S.

patients’ response to dotinurad with data generated in Japan, and to assess drug-drug interactions, if any, with allopurinol.

Urica expects to announce data from this trial in the first half of 2024.

MB-106 (CD20-targeted CAR T cell therapy)

Mustang is currently developing MB-106 in a collaboration with Fred Hutchinson Cancer Center (“Fred Hutch”), a CD20-targeted, 3rd generation autologous CAR T-cell therapy, for patients with relapsed or refractory B-cell non-Hodgkin lymphomas (“NHL”) and chronic lymphocytic leukemia (“CLL”).

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-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.

Fred Hutch intends to enroll approximately 50 subjects on the study, which is being led by Principal Investigator Mazyar Shadman, M.D., M.P.H., Assistant Member 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 Mustang.

In December 2023, Mustang announced initial data from its ongoing multicenter, open-label, non-randomized Phase 1/2 clinical trial (Clinicaltrials.gov Identifier:

NCT05360238) evaluating the safety and efficacy of MB-106 CAR-T cell therapy at the 2023 American Society of Hematology (“ASH”) Annual Meeting.

Initial data show that all patients responded clinically to treatment with MB-106 (n=9);

100% overall response rate for patients with follicular lymphoma (“FL”) and Waldenstrom macroglobulinemia (“WM”).

100% of patients with FL (n=5) had a complete response;

1 very good partial response and 2 partial responses were observed in WM patients (n=3);

and the hairy cell leukemia variant (“HCL-v”) patient experienced stable disease, with prolonged, ongoing independence from blood transfusions.

Complete responses were observed in patients previously treated with CD19-targeted CAR T-cell therapy.

MB-106 demonstrated a tolerable safety profile in patients with indolent NHL, with no occurrence of cytokine release syndrome (“CRS”) above grade 1 and no immune effector cell-associated neurotoxicity syndrome (“ICANS”) of any grade.

Outpatient administration was allowed and found to be feasible.

Information on clinicaltrials.gov does not constitute part of this Annual Report on Form 10-K.

In June 2023, Mustang announced final results from the FL cohort of the Fred Hutch Phase 1/2 clinical study, and the data showed an ORR of 95% (n=19/20) and complete response rate (“CR”) of 80% (n=16/20).

Ten patients were in remission for over one year, seven of whom were in remission for over two years.

All cytokine release syndrome events were grade1 (n=5/20) or grade 2 (n=1/20) with no grade 3 or higher cytokine release syndrome (“CRS”) events.

There was no occurrence of immune effector cell-associated neurotoxicity syndrome (“ICANS”) of any grade.

Through our subsidiary Urica Therapeutics, Inc.

(“Urica”), we acquired an exclusive license from Fuji Yakuhin Co.

(“Fuji”) to develop a URAT1 inhibitor product candidate in development for the treatment of gout, dotinurad, in North America, Europe, the Middle East and North Africa.

In July 2024, Urica entered into an asset purchase agreement, royalty agreement, and related agreements (collectively, the “Transaction Documents”) with Crystalys Therapeutics, Inc.

(“Crystalys”).

Crystalys is a Delaware corporation founded in 2023 and seeded by leading life sciences institutional investors.

Under the Transaction Documents, Urica transferred rights to dotinurad and related intellectual property, licenses and agreements to Crystalys.

In return, Crystalys issued to Urica shares of its common stock equal to 35% of Crystalys’ outstanding equity including certain anti-dilution provisions through the raise of $150 million in equity securities.

The Transaction Documents also granted Urica a secured 3% royalty on future net sales of dotinurad to be paid by Crystalys, and a right to receive nominal cash reimbursement payments for certain clinical and development costs incurred by Urica related to dotinurad.

Dotinurad was approved in Japan in 2020 as a once-daily oral therapy for gout and hyperuricemia and in China in December 2024 for the treatment of gout patients with hyperuricemia.

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

Mustang is also currently developing MB-101 for malignant brain tumors, including glioblastoma (“GBM”).

Mustang is currently developing MB-101 for malignant brain tumors, including glioblastoma (“GBM”).

MB-101 is an optimized CAR T product targeting IL13Rα2 on the surface of the malignant cells and incorporates enhancements in CAR T design and T cell engineering to improve antitumor potency and T cell persistence.

GBM is the most common brain and central nervous system (“CNS”) cancer, accounting for 49% of malignant primary brain and CNS tumors, 54% of all gliomas, and 16% of all primary brain and CNS tumors.

More than 14,490 new glioblastoma cases were predicted in the U.S.

Malignant brain tumors are the most common 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, 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.

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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NCT04661384);

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

ClinicalTrials.gov Identifier:

NCT04510051) sponsored by COH.

Information on clinicaltrials.gov does not constitute part of this Annual Report on Form 10-K.

The final planned MB-101 trial will be in combination with the HSV-1 oncolytic virus (MB-108) in treating patients with recurrent or refractory glioblastoma and anaplastic astrocytoma.

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MB-108 (HSV-1 Oncolytic Virus C134 for recurrent GBM)

MB-108 is a next-generation oncolytic herpes simplex virus (“oHSV”) in development at Mustang that is conditionally replication competent;

MB-108 is a next-generation oncolytic herpes simplex virus (“oHSV”) treatment in development at Mustang that is conditionally replication competent;

that is, it is designed to replicate in tumor cells, but not in normal cells, thus killing the tumor cells directly through this process.

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In addition, oncolytic viruses (“OVs”) have been developed to effectively infect and kill cancer cells in the tumor, as well as modify the microenvironment to increase tumor immunogenicity and immune cell trafficking within the tumor.

Due to these properties, OVs have been studied in combination with other treatments to enhance the effectiveness of immunotherapies.

these properties, OVs have been studied in combination with other treatments to enhance the effectiveness of immunotherapies.

Preliminary anti-tumor activity has been observed in clinical studies administering the OV (MB-108) and CAR T cell therapy (MB-101) as single agents;

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To determine if the combination of both therapies will result in a synergistic effect, investigators from COH developed preclinical studies in orthotopic GBM models in nude mice.

Christine Brown from City of Hope presented these preclinical studies at the American

Association for Cancer Research 2022 Annual Meeting.

Christine Brown from City of Hope presented these preclinical studies at the American Association for Cancer Research 2022 Annual Meeting.

It was observed that co-treatment with MB-108 OV and IL13Rα2-directed CAR-T cells gave no adverse events and, more notably, that pre-treatment with MB-108 re-shaped the tumor microenvironment by increasing immune cell infiltrates and enhanced the efficacy of sub-therapeutic doses of CAR-T cell therapy delivered either intraventricularly or intratumorally.

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Mustang is currently planning a Phase 1 clinical study that will investigate increasing doses of intratumorally administered MB-108 followed by dual intratumoral and intraventricular administration of MB-101 to treat recurrent GBM and high-grade astrocytomas that express IL13Rα2 on the surface of tumor cells.

In November 2024, Mustang announced that the FDA granted Orphan Drug Designation to Mustang for MB-108 for the treatment of malignant glioma.

Mustang is currently exploring with COH to conduct 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.

MB-106 (CD20-targeted CAR T cell therapy)

In the first quarter of 2024, Mustang 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 Waldenstrom macroglobulinemia (“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.

Due to limited resources, and as a result of the reduction in work force conducted in 2024, Mustang does not expect to initiate a pivotal Phase 2 single-arm clinical trial of MB-106 for the treatment of WM trial in 2025.

Also in the first quarter of 2024, Mustang completed enrollment of the indolent lymphoma arm in the 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, Mustang announced plans to collaborate with Fred Hutch for a proof-of-concept Phase 1 investigator-sponsored clinical trial evaluating MB-106 in autoimmune diseases.

Also in March 2024, Mustang was 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.

In June 2024, Mustang 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 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, Mustang 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 Mustang had decided to close the trial.

In June 2024, Mustang 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 Mustang 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.

AJ201 (Nrf1 and Nrf2 activator, androgen receptor degradation enhancer)

In February 2023, Avenue announced the license of intellectual property rights underlying AJ201 from AnnJi Pharmaceutical Co.

Ltd (“AnnJi”).

AJ201 is currently being studied in a Phase 1b/2a multicenter, randomized, double-blind clinical trial at six clinical sites across the U.S.

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NCT05517603).

Enrollment was completed in January 2024, with topline data anticipated in the second quarter of 2024.

Enrollment was completed in January 2024.

Information on clinicaltrials.gov does not constitute part of this Annual Report on Form 10-K.

SBMA is a rare, inherited, X-linked genetic neuromuscular disease primarily affecting men and AJ201 was designed to modify SBMA through multiple mechanisms including degradation of the abnormal AR protein and by stimulating Nrf1 and Nrf2, which are involved in protecting cells from oxidative stress which can lead to cell death.

AJ201 has been granted Orphan Drug Designation by the FDA for the indications of SBMA, Huntington’s Disease, and Spinocerebellar Ataxia.

MB-117 (Ex vivo Lentiviral Gene Therapy for Newly Diagnosed X-linked Severe Combined Immunodeficiency (“XSCID”)) and MB-217 (Ex vivo Lentiviral Gene Therapy for Previously Transplanted XSCID)

In partnership with St.

Jude, Mustang’s XSCID gene therapy programs are being developed under an exclusive license to intellectual property underpinning potentially curative treatment for XSCID, a rare genetic immune system condition in which affected patients do not live beyond infancy without treatment.

Jude’s first-in-class ex vivo lentiviral (“LV”) gene therapy has been utilized in two Phase 1/2 clinical trials involving two different autologous cell products produced via transduction of patients’ hematopoietic stem cells using a predecessor LV vector.

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:

referred to at St.

Jude as LVXSCID-ND) 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:

referred to at the NIH as LVXSCID-OC).

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.

In 2024, following availability of the modified LV vector, we expect that St.

Jude will initiate its Phase 1 trial to treat newly diagnosed infants with MB-117 and that the NIH will initiate its Phase 1 trial to treat previously transplanted patients with MB-217.

MB-110 (Ex Vivo Lentiviral Gene Therapy for RAG1 Severe Combined Immunodeficiency)

Mustang is developing MB-110, a first-in-class ex vivo treatment for recombinase-activating gene-1 (“RAG1”) Severe combined immunodeficiency (“SCID”), through an exclusive license and in partnership with Leiden University Medical Centre (“LUMC”).

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.

On March 3, 2025, Avenue received a “notice of intent to terminate” letter from AnnJi, the licensor of AJ201 , with respect to the license agreement under which Avenue was granted rights to the product candidate;

Avenue believes that the grounds for termination stated in the purported termination notice are without merit and intends to avail itself of the dispute resolution procedures set forth in the AJ201 license agreement.

Our partner company Avenue is developing an intravenous formulation of tramadol (“IV tramadol”), a schedule IV opioid for the treatment of post-operative acute pain.

Avenue completed two Phase 3 efficacy studies in 2018 and 2019 and announced that both had met their primary endpoints and all key secondary endpoints.

The FDA assigned a PDUFA goal date of April 12, 2021 for the resubmitted NDA for IV Tramadol.

On June 14, 2021, Avenue announced that the receipt of a second CRL.

Avenue submitted a formal dispute resolution request (“FDRR”) with the Office of Neuroscience of the FDA on July 27, 2021.

On August 26, 2021, Avenue received an Appeal Denied Letter from the Office of Neuroscience of the FDA in response to the FDRR submitted on July 27, 2021.

On August 31, 2021, Avenue submitted a FDRR with the Office of New Drugs (“OND”) of the FDA.

On October 21, 2021, Avenue received a written response from the OND of the FDA stating that the OND needs additional input from an Advisory Committee in order to reach a decision on the FDRR.

In February 2022, Avenue held an Advisory Committee meeting with the FDA regarding IV tramadol.

In the final part of the public meeting, the Advisory Committee voted yes or no on the following question:

“Has the Applicant submitted

adequate information to support the position that the benefits of their product outweigh the risks for the management of acute pain severe enough to require an opioid analgesic in an inpatient setting?” The results were 8 yes votes and 14 no votes.

In March 2022, Avenue received an Appeal Denied Letter from the Office of New Drugs in response to the formal dispute resolution request.

In August 2022, Avenue participated in a Type A Meeting with the FDA Division of Anesthesia, Analgesia, and Addiction Products (“DAAAP”) regarding a briefing document submitted that presented a study design Avenue believed would have the potential to address the comments and deficiencies noted in the Letter.

In January 2024, Avenue announced that they reached final agreement with the FDA on the Phase 3 safety study protocol and statistical analysis approach, including the primary endpoint.

The final non-inferiority study is designed to assess the risk of opioid-induced respiratory depression related to opioid stacking on IV tramadol compared to IV morphine.

The study will randomize approximately 300 post bunionectomy patients to IV tramadol or IV morphine for pain relief administered during a 48-hour post-operative period.

Of note, the same surgical model was used in a pivotal Phase 3 Trial.

In the Phase 3 safety study to be conducted, patients will have access to IV hydromorphone, a Schedule II opioid, for rescue of breakthrough pain.

The primary endpoint is a composite of elements indicative of respiratory depression.

Avenue plans to initiate the study in the future, subject to having the necessary financing.

BAER-101 (GABA A α2/3 positive allosteric modulator)

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Baergic intends to explore BAER-101 in a number of CNS disorders where patients are not adequately treated, including epilepsy and acute anxiety disorders.

In August 2023, Avenue reported preclinical data for BAER-101 from an in vivo evaluation in SynapCell’s Genetic Absence Epilepsy Rate from the Strasbourg (“GAERS”) model of absence epilepsy.

In August 2023, Avenue reported preclinical data for BAER-101 from an in vivo evaluation in SynapCell’s Genetic Absence Epilepsy Rate from Strasbourg (“GAERS”) model of absence epilepsy.

The GAERS model mimics behavioral, electrophysiological and pharmacological features of human absence seizures and has shown to be an early informative indicator of efficacy in anti-seizure drug development.

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In December 2023, Avenue presented the preclinical in vivo data evaluating BAER-101 using the GAERS model of absence epilepsy at the American Epilepsy Society (AES) 2023 Annual Meeting.

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

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.

Olafertinib has FDA Orphan Drug Designation for the treatment of EGFR mutation-positive NSCLC.

Preclinical Product Candidates

Mayo Clinic In Vivo CAR T Platform Technology

In August 2021, Mustang announced an exclusive license agreement with the 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.

Preclinical proof-of-concept has been established, and the ongoing development of this technology is continuing in partnership with the Mayo Clinic.

AAV-ATP7A Gene Therapy

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Patent and Trademark Office (“USPTO”) proceedings, if a generic company launches a competing product “at risk,” or when the regulatory or licensed exclusivity for our products (if applicable) expires or is otherwise lost, we may face generic competition as a result.

Generic versions are generally significantly less expensive than branded

versions, and, where available, may be required to be utilized before or in preference to the branded version under third-party reimbursement programs, or substituted by pharmacies.

Generic versions are generally significantly less expensive than branded versions, and, where available, may be required to be utilized before or in preference to the branded version under third-party reimbursement programs, or substituted by pharmacies.

Accordingly, when a branded product loses its market exclusivity, it normally faces intense price competition from generic forms of the product.

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The conduct of the preclinical tests must comply with federal regulations and requirements including GLPs.

The sponsor must submit the results of the preclinical tests, together with manufacturing information, analytical data, any available clinical data or

literature and a proposed clinical protocol, to the FDA as part of the IND.

The sponsor must submit the results of the preclinical tests, together with manufacturing information, analytical data, any available clinical data or literature and a proposed clinical protocol, to the FDA as part of the IND.

The IND automatically becomes effective 30 days after receipt by the FDA unless the FDA places the IND on a clinical hold within that 30-day time period.

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A sponsor may request the FDA to designate a platform technology as a designated platform technology concurrently with, or at any time after, submission of an IND application for a drug that incorporates or utilizes the platform technology that is the subject of the request.

If so designated, the FDA may expedite the development and review of any subsequent original NDA for a drug that uses or incorporates the platform technology.

If so designated, the FDA may expedite the development and review of any subsequent original NDA for a drug that uses or incorporates

the platform technology.

Designated platform technology status does not ensure that a drug will be developed more quickly or receive FDA approval.

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Section 505(b)(2) was added to the Act by the Drug Price Competition and Patent Term Restoration Act of 1984 (Hatch-Waxman Amendments).

Section 505(b)(2) of the FDCA provides an alternate regulatory pathway for approval of a new

drug by allowing the FDA to rely on data not developed by the applicant.

Section 505(b)(2) of the FDCA provides an alternate regulatory pathway for approval of a new drug by allowing the FDA to rely on data not developed by the applicant.

Specifically, Section 505(b)(2) permits the submission of an NDA where one or more of the investigations relied upon by the applicant for approval was not conducted by or for the applicant and for which the applicant has not obtained a right of reference.

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If an applicant has provided a Paragraph IV certification to the FDA, the applicant must also send notice of the Paragraph IV certification to the holder of the NDA for the approved drug and the patent owner once the application has been accepted for filing by the FDA.

The NDA holder or patent owner may then initiate a patent infringement lawsuit in response to notice of the Paragraph IV certification.

The NDA holder or patent owner may then initiate a patent infringement lawsuit in response to

notice of the Paragraph IV certification.

The filing of a patent infringement lawsuit within 45 days of the receipt of a Paragraph IV certification prevents the FDA from approving the ANDA or 505(b)(2) application until the earlier of 30 months from the date of the lawsuit, the applicant’s successful defense of the suit, or expiration of the patent.

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If a product that has an orphan drug designation is the first such product to receive FDA approval for the disease for which it has such designation, the product is entitled to orphan product exclusivity for that use.

This means that, subsequent to approval, the FDA may not approve any other applications to market the same drug that designated orphan use, except in

limited circumstances, for seven years.

This means that, subsequent to approval, the FDA may not approve any other applications to market the same drug that designated orphan use, except in limited circumstances, for seven years.

The FDA may approve a subsequent application from another person if the FDA determines that the application is for a different drug or different use, or if the FDA determines that the subsequent product is clinically superior, or that the holder of the initial orphan drug approval cannot assure the availability of sufficient quantities of the drug to meet the public’s need.

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Five-year and three-year exclusivity will not delay the submission or approval of a full NDA.

However, an applicant submitting a full NDA would be required to conduct or obtain a right of reference to all of the preclinical studies and adequate and well-controlled clinical trials necessary to demonstrate safety and effectiveness.

However, an applicant submitting a full NDA would be required to conduct or obtain a right of reference to all of the preclinical

studies and adequate and well-controlled clinical trials necessary to demonstrate safety and effectiveness.

Orphan drug exclusivity, as described below, may offer a seven-year period of marketing exclusivity, except in certain circumstances.

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Pediatric Information

Under the Pediatric Research Equity Act (“PREA”), NDAs and BLAs or supplements to NDAs and BLAs must contain data to assess the safety and effectiveness of the treatment for the claimed indications in all relevant pediatric subpopulations and to support dosing and administration for each pediatric subpopulation for which the treatment is safe

and effective.

The FDA may grant full or partial waivers, or deferrals, for submission of data.

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The laws that may affect our ability to operate include:

reward, or in return for, either (1) the referral of an individual to a person for furnishing any item or service for which payment is available under a federal health care program, or (2) the purchase, lease, order or recommendation thereof of any good, facility, service or item for which payment is available under a federal health care program;

● The federal Anti-Kickback Statute, which prohibits, among other things, persons from knowingly and willfully soliciting, receiving, offering or paying remuneration, directly or indirectly, in cash or in kind, to induce or reward, or in return for, either (1) the referral of an individual to a person for furnishing any item or service for which payment is available under a federal health care program, or (2) the purchase, lease, order or recommendation thereof of any good, facility, service or item for which payment is available under a federal health care program;

● The False Claims Act and civil monetary penalty laws, which prohibit, among other things, individuals or entities from knowingly presenting, or causing to be presented, false or fraudulent claims for payment from the federal government or making or using, or causing to be made or used, a false record or statement material to a false or fraudulent claim;

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The ACA, as well as other healthcare reform measures that may be adopted in the future, may result in more rigorous coverage criteria and additional downward pressure on the payments received for any approved drug.

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

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

We are unable to predict what these changes may look like in the future.

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The principal purpose of our equity incentive plan is to attract, retain, and motivate selected employees, consultants, and directors through the granting of share-based compensation awards and cash-based bonus awards.

Executive Officers of Fortress

The following table sets forth certain information about our executive officers as of December 31, 2023.

Rosenwald, M.D.

Chairman of the Board of Directors, President and Chief Executive Officer

Chief Financial Officer and Head of Corporate Development

George Avgerinos, Ph.D.

Senior Vice President, Biologics Operations

Executive Vice Chairman, Strategic Development

Rosenwald, M.D.

has served as a member of the Company’s Board of Directors since October 2009 and as Chairman, President and Chief Executive Officer of the Company since December 2013.

Rosenwald also currently serves as a member of the board of directors of Fortress partner companies Avenue (Nasdaq:

ATXI), Checkpoint (Nasdaq:

CKPT), Mustang (Nasdaq:

MBIO) and Journey (Nasdaq:

Additionally, Dr.

Rosenwald serves as a member of the board of directors of each of Fortress’ private subsidiaries (and has so served in each case since company inception).

From 1991 to 2008, Dr.

Rosenwald served as the Chairman of Paramount BioCapital, Inc.

Over the past 30 years, Dr.

Rosenwald has acted as a biotechnology entrepreneur and has been involved in the founding, recapitalization and sale of numerous public and private biotechnology and life science companies.

He received his B.S.

in finance from Pennsylvania State University and his M.D.

from Temple University School of Medicine.

David Jin h as served as our Chief Financial Officer since August 2022 and as Head of Corporate Development since May 2020.

He also serves as Interim Chief Financial Officer and Chief Operating Officer of Avenue.

Previously, he was on the investment team in the Private Equity & Real Assets group at Barings, Director of Corporate Development at Sorrento Therapeutics, Vice President of Healthcare Investment Banking at FBR & Co., and was in the management consulting group at IMS Health (now IQVIA).

He holds a B.S.

in Industrial Engineering & Management Sciences with a double-major in Mathematical Methods in the Social Sciences from Northwestern University.

George Avgerinos, Ph.D .

has served as our Senior Vice President, Biologics Operations since June 2013.

Avgerinos joined us from AbbVie, Inc., where he was Vice President, HUMIRA® Manufacturing Sciences and External Partnerships.

In his 22-year career at AbbVie, Inc., formerly Abbott Laboratories, formerly BASF Bioresearch Corporation (BASF), Dr.

Avgerinos was responsible for many aspects of biologics development and operations.

These included the HUMIRA® operations franchise, global biologics process and manufacturing sciences, biologics CMC, manufacturing operations, and third-party manufacturing.

During his tenure, Dr.

Avgerinos led and participated in the development of numerous clinical candidates which included the launch of HUMIRA®.

He supported expansion of the supply chain to over $9.0 billion in annual global sales.

Avgerinos’ efforts on HUMIRA® have been recognized with numerous awards, including the prestigious Abbott’s Chairman’s award in 2011.

Avgerinos received a B.A.

in Biophysics from the University of Connecticut and a Ph.D.

in Biochemical Engineering from the Massachusetts Institute of Technology.

Avgerinos also provides services for TG Therapeutics, Inc., a related party, pursuant to a shared services agreement.

Weiss has served as our Executive Vice Chairman, Strategic Development since February 2014.

He currently serves as a member of the board of directors of several of our partner companies, including Checkpoint (Nasdaq:

CKPT) and Mustang (Nasdaq:

Weiss is currently the Executive Chairman of Mustang Bio, Inc.

and the Chairman of the Board of Directors of Checkpoint.

From March 2015 until February 2019, Mr.

Weiss served on the board of Avenue (Nasdaq:

Since December 2011, Mr.

Weiss has served in multiple capacities at TG Therapeutics, Inc.

TGTX), a related party, and is currently its Executive Chairman, Chief Executive Officer and President.

Weiss founded Access Oncology, which was later acquired by Keryx Biopharmaceuticals (Nasdaq:

KERX) in 2004.

Following the merger, Mr.

Weiss remained as CEO of Keryx.

He began his professional career as a lawyer with Cravath, Swaine & Moore LLP.

Weiss earned his B.S.

in Finance from The University of Albany and his J.D.

from Columbia Law School.

Available Information

We and certain of our affiliates file annual reports on Form 10-K, quarterly reports on Form 10-Q, current reports on Form 8-K, proxy and information statements and amendments to reports filed or furnished pursuant to Sections 13(a), 14 and 15(d) of the Securities Exchange Act of 1934, as amended, or the Exchange Act.

The SEC also maintains a website at http://www.sec.gov that contains reports, proxy and information statements and other information regarding our Company and other companies that file materials with the SEC electronically.

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.

Copies of our and certain of our affiliates’ reports on Form 10-K, Forms 10-Q and Forms 8-K may also 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.

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What changed 10-K

Item 1. Business