On May 19, 2023 AbbVie (NYSE: ABBV) reported that the U.S. Food and Drug Administration (FDA) has approved EPKINLYTM (epcoritamab-bysp), as the first and only T-cell engaging bispecific antibody for the treatment of adult patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL), not otherwise specified (NOS), including DLBCL arising from indolent lymphoma, and high-grade B–cell lymphoma (HGBL), after two or more lines of systemic therapies (Press release, AbbVie, MAY 19, 2023, View Source [SID1234631879]). EPKINLY is approved under the FDA’s Accelerated Approval program based on response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. EPKINLY is being co-developed by AbbVie and Genmab as part of the companies’ oncology collaboration.

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DLBCL is a type of aggressive, fast-growing non-Hodgkin’s lymphoma (NHL), a cancer that develops in the lymphatic system and affects B cells, a type of white blood cell. DLBCL is the most common type of NHL, comprising of an estimated 30,400 U.S. cases in 2022 and 150,000 new cases each year globally. DLBCL patients are typically treated with chemoimmunotherapy-based regimens. For R/R patients, several targeted therapies including T-cell mediated treatments have recently emerged. However, single agent and ready-available or off-the-shelf treatment options are limited.1,2,3,4,5

"DLBCL is an aggressive cancer type that can rapidly progress and resist treatment. The FDA approval of EPKINLY represents a new treatment mechanism of action for third line DLBCL patients. As a non-chemotherapy, single-agent treatment for DLBCL patients, we hope that EPKINLY can effectively treat this aggressive cancer type and can be used for patient care quickly and in an off the shelf form for physicians," said Thomas Hudson, M.D., senior vice president, research and development, chief scientific officer, AbbVie. "The approval is just the first step, with our partner Genmab, towards a shared goal of developing a core therapy for patients with B-cell malignances."

AbbVie is committed to transforming standards of care across blood cancers and advancing a dynamic cancer research and treatment pipeline. EPKINLY marks the third approved blood cancer treatment available as part of AbbVie’s growing oncology portfolio, as we strive to make a remarkable impact for people living with cancer.

"Patients with DLBCL who relapse or are refractory to currently available therapies have limited options. Generally, the prognosis for these patients is poor and management of this aggressive disease can be challenging," said Tycel Phillips, M.D., City of Hope Associate Professor, Division of Lymphoma, Department of Hematology & Hematopoietic Cell Transplantation. "Epcoritamab is a subcutaneous bispecific antibody that offers an additional treatment option for this patient population. With this approval, patients who are in need of additional therapy may have the opportunity to receive epcoritamab after failure to respond or relapse after two or more systemic therapies."

"The FDA approval of EPKINLY represents a new treatment for diffuse large B-cell lymphomas among patients who have relapsed or have refractory disease and are looking for a new medication," said Meghan Gutierrez, chief executive officer, Lymphoma Research Foundation.

Highlights of the Phase 1/2 EPCORE NHL-1 clinical trial supporting the approval:

In the expansion cohort of the EPCORE NHL-1 trial, 148 patients with CD20+ DLBCL were enrolled, 86 percent of which were diagnosed with DLBCL NOS, including 27 percent with DLBCL transformed from indolent lymphoma, and 14 percent with HGBL. The median number of prior therapies was three (range: 2 to 11), with 30 percent receiving two prior therapies, 30 percent receiving three prior therapies, and 40 percent receiving four or more prior therapies. Eighteen percent had prior autologous hematopoietic stem cell transplantation (HSCT), and 39 percent had prior chimeric antigen receptor (CAR)T-cell therapy. Eighty-two percent of patients had disease refractory to last therapy and 29 percent of patients were refractory to CAR T-cell therapy.
EPKINLY delivered an overall response rate of 61 percent, a complete response rate of 38 percent and median duration of response of 15.6 months in heavily pretreated R/R DLBCL patients.
The prescribing information has a Boxed Warning for serious or life-threatening cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Warnings and precautions include infections, cytopenias, and embryo-fetal toxicity. The most common (≥ 20 percent) adverse reactions were CRS, fatigue, musculoskeletal pain, injection site reactions, pyrexia, abdominal pain, nausea, and diarrhea. Please see additional Important Safety Information, below.
About EPKINLYTM (epcoritamab-bysp)
EPKINLY is a prescription medicine used to treat adults with certain types of diffuse large B-cell lymphoma (DLBCL) and high-grade B-cell lymphoma (HGBL) that has come back (relapsed) or that did not respond to previous treatment (refractory), and who have received 2 or more treatments for their cancer. EPKINLY is approved based on patient response data. A study is ongoing to confirm the clinical benefit of EPKINLY. It is not known if EPKINLY is safe and effective in children.

EPKINLY is an IgG1-bispecific antibody created using Genmab’s proprietary DuoBody technology. Genmab’s DuoBody-CD3 technology is designed to direct cytotoxic T cells selectively to elicit an immune response towards target cell types. It is designed to simultaneously bind to CD3 on T cells and CD20 on B-cells and induces T cell mediated killing of CD20+ cells.5,6,7

AbbVie and Genmab are evaluating EPKINLY as a monotherapy, and in combination, across multiple lines of therapy in a range of hematologic malignancies. This includes an ongoing Phase 3, open-label, randomized controlled trial evaluating EPKINLY as a monotherapy in patients with R/R DLBCL (NCT: 04628494) and two Phase 3, open-label, randomized controlled trials evaluating EPKINLY combination regimens in patients with newly diagnosed DLBCL (NCT: 05660967) and R/R follicular lymphoma (NCT: 05409066). The companies will share commercial responsibilities in the U.S. and Japan, with AbbVie responsible for further global commercialization. AbbVie will continue to pursue regulatory submissions for epcoritamab across international markets throughout the year.

IMPORTANT SAFETY INFORMATION

Important Warnings—EPKINLY can cause serious side effects, including:

Cytokine Release Syndrome (CRS). CRS is common during treatment with EPKINLY and can be serious or life-threatening. Tell your healthcare provider or get medical help right away if you develop symptoms of CRS, including fever of 100.4°F (38°C) or higher, dizziness or lightheadedness, trouble breathing, chills, fast heartbeat, feeling anxious, headache, confusion, shaking (tremors), or problems with balance and movement, such as trouble walking.

Due to the risk of CRS, you will receive EPKINLY on a "step-up" dosing schedule. The step-up dosing schedule is when you receive smaller "step-up" doses of EPKINLY on day 1 and day 8 of your first cycle of treatment (cycle 1). You will receive your first full dose of EPKINLY on day 15 of cycle 1. If your dose of EPKINLY is delayed for any reason, you may need to repeat the step-up dosing schedule. Before each dose in cycle 1, you will receive medicines to help reduce your risk of CRS. Your healthcare provider will decide if you need to receive medicine to help reduce your risk of CRS with future cycles.

Neurologic problems. EPKINLY can cause serious neurologic problems that can be life-threatening and lead to death. Neurologic problems may happen days or weeks after you receive EPKINLY. Your healthcare provider may refer you to a healthcare provider who specializes in neurologic problems. Tell your healthcare provider right away if you develop any symptoms of neurologic problems, including trouble speaking or writing, confusion and disorientation, drowsiness, tiredness or lack of energy, muscle weakness, shaking (tremors), seizures, or memory loss.
Due to the risk of CRS and neurologic problems, you should be hospitalized for 24 hours after receiving your first full dose of EPKINLY on day 15 of cycle 1. Your healthcare provider will monitor you for symptoms of CRS and neurologic problems during treatment with EPKINLY, as well as other side effects, and treat you if needed. Your healthcare provider may temporarily stop or completely stop your treatment with EPKINLY if you develop CRS, neurologic problems, or any other side effects that are severe.

Do not drive or use heavy or potentially dangerous machinery if you develop dizziness, confusion, tremors, drowsiness, or any other symptoms that impair consciousness until your symptoms go away. These may be symptoms of CRS or neurologic problems.

EPKINLY can also cause other serious side effects, including:

Infections. EPKINLY can cause serious infections that may lead to death. Your healthcare provider will check you for symptoms of infection before and during treatment. Tell your healthcare provider right away if you develop any symptoms of infection during treatment, including fever of 100.4°F (38°C) or higher, cough, chest pain, tiredness, shortness of breath, painful rash, sore throat, pain during urination, or feeling weak or generally unwell.
Low blood cell counts. Low blood cell counts are common during treatment with EPKINLY and can be serious or severe. Your healthcare provider will check your blood cell counts during treatment. EPKINLY may cause low blood cell counts, including low white blood cell counts (neutropenia), which can increase your risk for infection; low red blood cell counts (anemia), which can cause tiredness and shortness of breath; and low platelet counts (thrombocytopenia), which can cause bruising or bleeding problems.
Your healthcare provider may temporarily stop or completely stop treatment with EPKINLY if you develop certain side effects.

Before you receive EPKINLY, tell your healthcare provider about all of your medical conditions, including if you:

have an infection.
are pregnant or plan to become pregnant. EPKINLY may harm your unborn baby. Females who are able to become pregnant: Your healthcare provider should do a pregnancy test before you start treatment with EPKINLY. You should use effective birth control (contraception) during treatment and for 4 months after your last dose of EPKINLY. Tell your healthcare provider if you become pregnant or think that you may be pregnant during treatment with EPKINLY.
are breastfeeding or plan to breastfeed. It is not known if EPKINLY passes into your breast milk. Do not breastfeed during treatment with EPKINLY and for 4 months after your last dose of EPKINLY.
Tell your healthcare provider about all of the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

The most common side effects of EPKINLY include CRS, tiredness, muscle and bone pain, injection site reactions, fever, stomach-area (abdominal) pain, nausea, and diarrhea.

These are not all the possible side effects of EPKINLY. Call your doctor for medical advice about side effects.

You are encouraged to report side effects to the FDA at (800) FDA-1088 or www.fda.gov/medwatch or to Genmab US, Inc. at 1-855-4GENMAB (1-855-443-6622).

Please see Medication Guide, including Important Warnings.

On May 19, 2023 2seventy bio, Inc. (Nasdaq: TSVT), a leading immuno-oncology cell therapy company, reported late-breaking results from the ongoing Phase 1 PLAT-08 trial, in collaboration with Seattle Children’s Therapeutics, evaluating SC-DARIC33 in relapsed or refractory pediatric and young adult AML patients, as well as an oral presentation evaluating regulated IL-15 production combined with DARIC33 activation for anti-AML potency (Press release, 2seventy bio, MAY 19, 2023, View Source [SID1234631878]). The data were presented at this year’s American Society of Gene & Cell Therapy (ASGCT) (Free ASGCT Whitepaper) Annual Meeting in Los Angeles, California.

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"The treatment of patients with relapsed and refractory AML represents a tremendous unmet medical need, particularly for pediatric and young adult patients. Progressing the promise of CAR T therapy, while mitigating potentially dose-limiting toxicity, has the potential to be a meaningful advance," said Steven Bernstein, M.D., chief medical officer, 2seventy bio. "Together with Seattle Children’s Therapeutics, we are pleased to share results that demonstrate three key steps toward clinically meaningful outcomes: rapamycin dosing optimization, rapamycin-regulated in vivo expansion and activation of SC-DARIC33 T cells as well as concurrent anti-CD33 activity. These data reinforce the potential of SC-DARIC333 as a new T cell therapy approach in AML."

SC-DARIC33 is an investigational CD33-targeted chimeric antigen receptor (CAR) T cell therapy that utilizes 2seventy bio’s proprietary Dimerizing Agent Regulated Immunoreceptor Complex (DARIC) T cell platform, a drug regulatable CAR T cell technology. SC-DARIC33 has been shown to be activated by low non-immunosuppressive concentrations of rapamycin in the blood and, when rapamycin is removed, DARIC returns to an inactive state. SC-DARIC33 tests the hypothesis that a pharmacologically regulated CAR can enable potent AML targeting while limiting toxicities associated with normal myeloid and myeloid progenitor cell targeting.

Eligible patients in the ongoing Phase 1 PLAT-08 trial are 30 years of age or younger in first early relapse (less than 6 months), first relapse refractory to reinduction, or ≥ second relapse.

Following lymphodepletion (LD) with fludarabine/cyclophosphamide, patients received SC-DARIC33 T cells followed by rapamycin to activate SC-DARIC33. Primary objectives include assessment of safety and toxicity of SC-DARIC33, as well as the feasibility of manufacturing. Secondary objectives include assessment of efficacy, as well as engraftment, expansion, persistence, and activation states of SC-DARIC33 T cells.

As of March 17, 2023, three participants had received cell product infusion at 1 x 106 SC-DARIC33 T cells /kg (dose level 1) following LD chemotherapy. Infusions were generally well tolerated without occurrence of dose-limiting toxicities.

Preclinical studies predicted that DARIC33 dimerization, activation and expansion would occur at rapamycin trough levels in the range of ~1.5-3 ng/ml, well below the trough levels associated with immune suppression. Such levels were not achieved in the initial patient; however, after adjusting rapamycin monitoring and dosing algorithm, these levels were attained in the next two patients. As anticipated, attainment of such levels was associated with DARIC33 dimerization, activation, engagement of antigen and elicitation of CD33 expressing leukemic cell cytotoxicity. Of the two patients who achieved target rapamycin trough levels, the first one had extramedullary leukemia, and in this patient, we were able to infiltrate, activate and expand DARIC33 cells within an extramedullary leukemic infiltrate in the skin, resulting in hemorrhagic necrosis of this infiltrate. In the second patient, we saw DARIC33 expansion in the peripheral blood, peaking nine days after DARIC33 infusion, where 6.1% of the total lymphocytes were DARIC33 cells. The expansion of DARIC33 was associated with a significant transient reduction in the CD33 leukemic burden in the blood. Taken together, we believe this indicates at this very low cell dose that we can dose rapamycin to target levels resulting in the activation and expansion of DARICC33 cells which can then traffic to, engage, and kill leukemia cells.

In a separate oral presentation, researchers evaluated whether regulated IL-15 production combined with drug-controlled DARIC33 activation could enhance anti-AML potency without driving uncontrolled T cell growth or severe toxicity in the preclinical setting. Genetic modules were designed in which a novel synthetic promoter (iSynPro or iSP) transiently drove transcription of a modified IL-15 variant that further restricts IL-15 signaling to cells expressing IL-15Ra. The DARIC33 and iSP-IL-15 DARIC33 CAR T cells had similar expansion and phenotype characteristics during initial manufacturing and T cell activation with tumor cells resulted in rapamycin-dependent secretion of IL-15 in vitro and robust T cell expansion. When IL-15 was omitted from the culture media, iSP-IL-15 DARIC33 demonstrated enhanced expansion following tumor exposure but normal contraction kinetics, suggesting that iSP transcription may enhance T cell function through tightly regulated IL-15 production without promoting unrestrained T cell growth. Further, when AML tumor bearing mice were treated with DARIC33 with or without iSP-IL-15, we observed that both controlled tumor growth, but only iSP-IL-15 DARIC33 CAR T cells controlled tumor growth at a limiting cell dose.

These results demonstrate that Seattle Children’s proprietary iSynPro-regulated expression combined with rapamycin-controlled DARIC33 activation has the potential to enhance T cell function while preventing unrestrained T cell outgrowth.

About PLAT-08

PLAT-08, the Phase 1 study of SC-DARIC33 in relapsed/refractory pediatric AML, led by Seattle Children’s Therapeutics, couples 2seventy bio’s DARIC T cell platform with Seattle Children’s world-class bench-to-bedside expertise in oncology cell therapies. This study is a first-in-human investigation of the DARIC T cell platform and is now open for enrollment at Seattle Children’s.

PLAT-08 is enrolling pediatric and young adult patients with relapsed or refractory CD33+ leukemia with and without prior history of allogeneic hematopoietic cell transplantation, to examine the safety and feasibility of administering an autologous T cell product that has been genetically modified to express a Dimerizing Agent Regulated Immunoreceptor Complex (DARIC).

For more information visit: clinicaltrials.gov using identifier NCT05105152.

About SC-DARIC33

2seventy bio is collaborating with Seattle Children’s Therapeutics to rapidly accelerate development of potential new therapies for patients with acute myeloid leukemia (AML). This research collaboration is investigating potential solutions to two challenges in treating AML: disease heterogeneity and toxicity due to shared expression of targets between tumor and normal tissue.

SC-DARIC33 is an investigational, pharmacologically controlled CD33-targeted autologous T cell product that utilizes 2seventy bio’s proprietary Dimerizing Agent Regulated Immunoreceptor Complex (DARIC) T cell platform, a regulatable CAR T cell technology. DARIC T cells are intended to be switched from "OFF" to "ON" in the presence of rapamycin, such that while in the "ON" state the T cell is poised to be activated upon encounter with its target antigen.

SC-DARIC33 is not approved for any indication in any geography.

On May 19, 2023 Imugene Limited (ASX:IMU), a clinical stage immuno oncology company, reported that it has received US Food and Drug Administration (FDA) Investigational New Drug (IND) clearance to initiate a Phase 1 clinical study of its oncolytic virotherapy candidate, onCARlytics (on-CAR-19, CF33-CD19, HOV4) (Press release, Imugene, MAY 19, 2023, View Source [SID1234631874]).

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The FDA clearance of the IND allows Imugene to start patient recruitment and dosing in a first-in-class Phase 1 clinical study for the onCARlytics platform in patients with solid tumours: "A Phase I, Dose Escalation and Dose Expansion, Safety and Tolerability Study of onCARlytics (CF33-CD19), Administered Intravenously or Intratumorally in Combination with Blinatumomab in Adults with Advanced or Metastatic Solid Tumors (OASIS)."

Imugene’s CF33-CD19 oncolytic virus, when combined with the CD19 targeting bispecific monoclonal antibody blinatumomab (Blincyto), has the potential to target and eradicate solid tumours that otherwise cannot be treated with Blincyto therapy alone.

On May 18, 2023 Pacylex Pharmaceuticals, a clinical-stage company developing PCLX-001, a first-in-class oral investigational small molecule for leukemia, lymphoma, and solid tumor cancers, reported the first patient has been dosed in a Phase 2a expansion study in patients with relapsed/refractory B-cell Non-Hodgkin Lymphoma (R/R NHL) (Press release, Pacylex Pharmaceuticals, MAY 18, 2023, View Source [SID1234645057]).

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The Company’s Phase 1 multiple ascending dose (MAD) clinical trial evaluating PCLX-001 monotherapy in patients with R/R NHL or advanced solid tumors successfully completed six dose escalations without any dose-limiting toxicities (DLTs) and reached a drug exposure level expected to show clinical activity. Three patients with advanced solid tumors in the highest dose level are continuing to receive PCLX-001.

The Company received a No Objection Letter from Health Canada earlier this year to initiate the expansion cohort, designed to evaluate a potential Phase 2 dose in patients with R/R NHL. Four Canadian clinical sites have been activated and the first patient has been dosed. The expansion study will enroll up to 20 patients to assess the preliminary clinical activity of PCLX-001.

"The first stage of this first-in-human study assessed the safety of PCLX-001 with repeated dosing. We now transition our clinical investigations from primarily establishing safety to both safety and efficacy at a potential Phase 2 dose," said Dr. John Mackey, CMO of Pacylex.

"This milestone represents a major step in the development of PCLX-001 as a first-in-class oral cancer therapy" said Pacylex CEO Dr. Michael Weickert. "Our pre-clinical work showed that PCLX-001 at an equivalent dose in animals regressed R/R NHL tumors so it is exciting to see these patients finally receiving this as an investigational therapy" added Dr. Luc Berthiaume, Pacylex CSO and Professor at the University of Alberta.

Twenty-one patients have received PCLX-001 through 6 dose level escalations with no dose limiting toxicities, therefore dose escalation will continue in patients with advanced solid tumors in parallel with the Phase 2a study in patients with R/R NHL. Pacylex anticipates that it will present an update from the Phase 1 dose escalation portion of the study at a scientific conference this year.

About PCLX-001
PCLX-001 is a first-in-class, oral, small molecule N-myristoyltransferase (NMT) inhibitor being developed to treat patients with leukemia and lymphoma. PCLX-001 selectively kills cancer cells in vitro and have been shown to regress hematologic malignancies and inhibit the growth of lung and breast cancer tumors in animal models. PCLX-001 appears to be particularly effective against Acute Myeloid Leukemia (AML) stem cells in animal disease models.
The Phase 1/2a study (NCT04836195) is an open-label study designed to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and clinical activity of PCLX-001 in patients with R/R NHL and advanced solid malignancies who have progressed on all available standard therapies.

On May 18, 2023 Mustang Bio, Inc. ("Mustang" or the "Company") (Nasdaq: MBIO), a clinical-stage biopharmaceutical company focused on translating today’s medical breakthroughs in cell and gene therapies into potential cures for difficult-to-treat cancers and rare genetic diseases, reported a strategic update, including anticipated milestones for 2023 (Press release, Mustang Bio, MAY 18, 2023, View Source [SID1234633166]). Mustang intends to optimize the allocation of its resources and focus on MB-106, MB-109, and in vivo CAR T platform technology. Additionally, Mustang announced a partnership with uBriGene (Boston) Biosciences Inc. ("uBriGene"), the U.S. subsidiary of uBriGene Group, a leading cell and gene therapy contract development and manufacturing organization ("CDMO"), which includes the sale of the Company’s development, manufacturing and analytical testing facility in Worcester, Massachusetts to uBriGene.

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Under the terms of an asset purchase agreement between Mustang and uBriGene, uBriGene will acquire Mustang’s state-of-the-art clinical- and commercial-scale cell and gene therapy manufacturing facility in Worcester, Massachusetts, for a total consideration of $11 million. This consideration includes $6 million payable upfront plus an additional $5 million payable upon Mustang raising $10 million in gross proceeds from equity raises following the closing of the transaction. The closing of the transaction is subject to the satisfaction of certain conditions, including approval of transfer of the Company’s lease to uBriGene by the owner of the building (an affiliate of the University of Massachusetts Chan Medical School) and the acceptance of offers of employment with uBriGene or its affiliates by certain key current Mustang employees. Subject to satisfaction of conditions, the Company expects the transactions to close in June 2023.

Subject to closing, the parties will enter into a manufacturing supply agreement, under which uBriGene will manufacture Mustang’s lead product candidates, including continuing to support MB-106 manufacturing for the ongoing multi-center Phase 1/2 trial.

Mustang’s Worcester facility is a 27,000 square foot, cutting edge cGMP facility supporting process development, manufacturing and analytical testing, designed with the flexibility to expand and support various cell and gene therapy production requirements and capacities. uBriGene intends to expand the Worcester site’s capabilities while leveraging Mustang’s experienced staff and robust quality and operating systems to manufacture a broader portfolio of advanced modalities. uBriGene will also offer their expertise in preclinical research services and late-stage and commercial manufacturing of advanced therapy products with respect to product and process characterization, and regulatory inspections.

Manuel Litchman, M.D., President and Chief Executive Officer of Mustang, commented, "We are very pleased to have found a great partner for the manufacturing of our CAR T cell and gene therapies, and we believe that this strategic partnership with uBriGene will meet our portfolio manufacturing needs to reach critical upcoming data inflection points, while extending our cash runway. I want to thank our manufacturing team for their dedication in building and growing our Worcester facility since it opened in 2018. While we are optimizing our resources at Mustang, we look forward to continuing to work with many of our colleagues in this new capacity, as our CDMO."

"This acquisition is important to uBriGene’s commitment to support the development, clinical, and commercial supply of cell and gene therapies to sustain industry demand and provide new CDMO options," said Alex Chen, President of uBriGene. "We look forward to working together with the University of Massachusetts Chan Medical School and local biotechnology companies to continue to advance the manufacturing ecosystem in the Greater Boston region. This partnership enables us to expand rapidly to create a North American presence and offer the same high-quality cell and gene therapy development and manufacturing capabilities for the U.S. that we currently provide in Asia, including to support Mustang Bio’s lead clinical-stage CAR-T program."

Mustang Bio Strategic Portfolio Updates

CAR T Cell Therapies
After a review of its portfolio of product candidates to determine the future strategy of its programs and the proper allocation of its resources, Mustang will discontinue development of its MB-102, its CD123-targeted CAR T cell therapy, as well as its HER2-, CS1- and PSCA-targeted CAR T cell therapy programs, comprising a portion of the Company’s portfolio of CAR T cell therapies being developed by the Company in partnership with City of Hope.

Mustang will continue to work with Fred Hutchinson Cancer Center ("Fred Hutch") to develop MB-106 (CD20-targeted CAR T cell therapy) and with Mayo Clinic to develop its in vivo CAR T platform technology. Mustang will also continue to work with City of Hope and with Nationwide Children’s Hospital on the development of MB-109 (MB-101 CAR T cell therapy targeting IL13Rα2 on malignant glioma cells + MB-108 oncolytic virus to potentially make these tumors more susceptible to killing by the CAR-T cells).

Gene Therapies
Additionally, based on a review of the data from the investigator-sponsored clinical trials of the gene therapy for X-linked severe combined immunodeficiency ("XSCID") that has been licensed to Mustang Bio, enrollment to these trials has been paused. We await data from new investigator-sponsored trials being planned by our partners that will test a modified version of the current lentiviral vector prior to initiating multicenter Mustang-sponsored trials in both the newborn and previously transplanted patient populations. No safety concerns in the trials utilizing the current vector have been noted to date and no insertional mutagenesis or malignancy has been detected in either of the two investigator-sponsored trials. However, Mustang has made the decision to delay initiating its own sponsored trials out of an abundance of caution, and once we have had the opportunity to review the emerging data from the planned trials utilizing the modified vector, Mustang expects to provide more information on timelines. The delayed start of Mustang’s multicenter trials for XSCID will allow the Company to utilize the safest known vector available in its clinical trials and reduce Mustang’s near-term operating expense.

In addition, in 2023 we look forward to treating a second RAG1-SCID patient with our MB-110 LV-RAG1 ex vivo lentiviral gene therapy in the ongoing investigator-sponsored Phase 1/2 multicenter clinical trial taking place in Europe. Furthermore, we hope to provide an update regarding the research collaboration with Frank J. Staal, Ph.D., from Leiden University to develop additional lentiviral gene therapies.

"Upon completion of a thorough, strategic review of our portfolio of CAR T and gene therapies, it was determined that Mustang’s resources should be focused and allocated to benefit our lead clinical-stage CAR T programs, which could provide potential curative treatment options for certain hematologic cancers and solid tumors, supported by data-to-date. As previously reported, MB-106 continues to demonstrate high efficacy and a favorable safety profile in a Phase 1 investigator-sponsored trial at Fred Hutch, with an overall response rate of 96% and complete response rate of 75% in a wide range of hematologic malignancies, including Waldenstrom macroglobulinemia ("WM"). Given this, Mustang plans to treat patients with WM in the Phase 1 portion of its multicenter MB-106 clinical trial to support a fast-to-market Phase 2 strategy for this indication, with the first pivotal Phase 2 WM patient potentially to be treated in the first quarter of 2024. Data from the Fred Hutch clinical trial also support the potential of MB-106 to be administered as outpatient therapy and provide a best-in-class immunotherapy option for patients treated previously with CD19-directed CAR T cell therapy. We look forward to data from the Fred Hutch clinical trial to be presented at medical meetings in the second quarter of 2023, and initial data from Mustang’s multicenter clinical trial to be disclosed shortly as well. Phase 1 clinical trials of MB-101 at City of Hope and of MB-108 at the University of Alabama at Birmingham continue to enroll patients with recurrent GBM. Additionally, Mustang is excited about advancing the preclinical investigation of these two programs as the combination therapy MB-109 and plans to file an IND for this therapy this year. Concentrating our priorities and postponing the initiation of the MB-107 and MB-207 pivotal trials, along with maintaining a reduced headcount, reduces Mustang’s burn and extends our cash runway. This allows Mustang to allocate more resources to advance our lead clinical-stage programs and potentially expedite the achievement of several near-term milestones across our portfolio of product candidates for difficult-to-treat cancers," said Dr. Litchman.

General Corporate
Mustang expects to incur severance charges related to the facility transaction of approximately $2.1 million, which Mustang expects will be offset by future annualized operating savings of at least $24 million including savings related to personnel, facility and clinical operations and optimization of the development portfolio. The Company also reduced annual interest expense by approximately $4.3 million in April 2023 after repaying and terminating its Loan and Security Agreement with Runway Growth Finance Corp.