On December 19, 2022 Mustang Bio, Inc. ("Mustang") (Nasdaq: MBIO), a clinical-stage biopharmaceutical company focused on translating today’s medical breakthroughs in cell and gene therapies into potential cures for hematologic cancers, solid tumors and rare genetic diseases, reported recent CAR T cell therapy portfolio updates and provided anticipated milestones for 2023 (Press release, Mustang Bio, DEC 19, 2022, View Source [SID1234625420]).

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Manuel Litchman, M.D., President and Chief Executive Officer of Mustang, said, "In 2022, Mustang successfully advanced our CAR T cell therapy portfolio which has laid the foundation for us to achieve multiple milestones in the coming year. Our lead clinical candidate, MB-106, a first-in-class CD20-targeted, autologous CAR T cell therapy for the treatment of relapsed or refractory B-cell non-Hodgkin lymphomas ("B-NHL") and chronic lymphocytic leukemia ("CLL"), continues to progress in our multicenter Phase 1/2 clinical trial. We’re pleased to report that Mustang has met its accrual target for the year for that trial and has manufactured product for all enrolled patients. We look forward to providing first safety and efficacy data in 2023. Additionally, data from the initial ongoing Phase 1/2 clinical trial taking place at Fred Hutchinson Cancer Center ("Fred Hutch") continue to exhibit high efficacy and a favorable safety profile compared to currently approved autologous CAR Ts. In particular, while other cell therapies in development have struggled to show durability of response, we reported in October that twelve of 28 patients enrolled had experienced complete remission (CR) for more than 12 months (10 ongoing), four patients had experienced CR for more than 2 years (all ongoing), and the first patient enrolled was in sustained CR at 33 months."

"In 2023, we anticipate filing an Investigational New Drug application ("IND") for our combination therapy MB-109 to treat glioblastoma ("GBM"). Additionally, we continue to collaborate with the Mayo Clinic to progress our exclusively licensed novel in vivo CAR T technology platform and anticipate the publication of proof-of-concept research in a murine tumor model. We’re looking forward to another productive year across our CAR T therapy programs, as we continue working with our world-class partners to advance therapies for difficult-to-treat cancers and rare diseases," said Dr. Litchman.

CAR T Candidate Portfolio Highlights:

MB-106 (first-in-class CD20-targeted, autologous CAR T cell therapy)
To date, six patients have been enrolled in Mustang’s multicenter Phase 1/2 clinical trial and five patients have been infused at the starting dose levels of their respective protocol arms. Mustang has successfully manufactured product for all enrolled patients at its facility in Worcester, MA. In 2023, the Company anticipates dose escalation and reporting response data at a major medical meeting.

As previously reported, MB-106 continues to demonstrate high efficacy and a favorable safety profile across patients with a wide range of hematologic malignancies in a Phase 1 investigator-sponsored trial at Fred Hutch, including a 100% overall response rate in patients with Waldenstrom macroglobulinemia ("WM"), a rare form of blood cancer. Given this, Mustang plans to treat patients with WM in the Phase 1 portion of its multicenter clinical trial to support a fast-to-market Phase 2 strategy for this indication. 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. In 2023, Mustang anticipates the U.S. Food and Drug Administration granting Orphan Drug Designation in at least one additional CD20 positive malignancy.

MB-109 (MB-101 (IL-13Rα2 targeted CAR T cell therapy) + MB-108 oncolytic virus)
Preclinical data presented at American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2022 ("AACR") supported this combination therapy to optimize results to treat recurrent GBM. The combination leverages MB-108 to make cold tumors "hot," thereby improving the efficacy of MB-101 CAR T cell therapy. Data presented separately on MB-101 and MB-108 showed infusions were well tolerated in highly refractory GBM patients. Two patients treated solely with MB-101 who had high levels of intratumoral CD3+ T cells pre-therapy (i.e., "hot" tumors) achieved complete responses lasting 7.5 and 31+ months, respectively. 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. Additionally, Mustang will advance the preclinical investigation of MB-109 and plans to file an IND for this treatment in 2023.

MB-102 (CD123-targeted CAR T cell therapy)
The Safety Review Team ("SRT") composed of Investigators and Mustang representatives recently met to assess the progress and safety data from the ongoing Mustang-sponsored, open label, multicenter Phase 1/2 clinical trial to evaluate the safety and efficacy of MB-102 in patients with relapsed or refractory blastic plasmacytoid dendritic cell neoplasm ("BPDCN"), a rare form of leukemia. After thoroughly reviewing the safety data from Dose Level 1 (100 x 106 CAR T cells), the SRT unanimously recommended dose escalation to Dose Level 2 (300 x 106 CAR T cells). There are currently no curative treatments for BPDCN. The trial continues to enroll and study sites include City of Hope, where the CAR T cell therapy was initially developed, Dana-Farber Cancer Institute, Duke University and The University of Texas MD Anderson Cancer Center. The MB-102 clinical trial is the first under Mustang’s IND in which a patient was dosed with cells processed in its own manufacturing facility. In 2023, Mustang expects to provide information about Dose Level 2 after that level is fully enrolled and the SRT has reviewed the data.

In vivo CAR-T platform technology
Mustang executed an exclusive license agreement with Mayo Clinic for this novel technology that may transform the administration of CAR T therapies. The Mayo approach involves activating immune cells in vivo using natural methods employed by the body to deal with infection, thus having the potential to reduce toxicities associated with traditional CAR T therapy. Successful implementation of this technology could lead to an off-the-shelf product with no need to isolate and expand patient T cells ex vivo in a manufacturing facility. Published proof-of-concept data from murine tumor model studies are anticipated in 2023. Additionally, Mustang plans to file an IND application for a multicenter Phase 1 clinical trial once a lead CAR construct has been identified.