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
difficult-to-treat cancers and rare genetic diseases, today
announced Phase 1 clinical data were published in Nature Medicine
that demonstrated the promising safety and clinical activity of
Mustang’s MB-101 (IL13Ra2-targeted CAR T-cells) for the treatment
of patients with recurrent and refractory malignant glioma,
including glioblastoma.
MB-101 was developed by City of Hope, one of the
largest cancer research and treatment organizations in the United
States, and exclusively licensed to Mustang.
Highlights from the data
include:
- Stable disease or better was
achieved in 50% (29/58) of heavily pretreated patients for at least
two months, with two partial responses, one complete response (CR),
and a second CR after additional CAR-T cycles under compassionate
use.
- Patients with recurrent GBM treated
in the final cohort with dual intratumoral (ICT)/ intraventricular
(ICV) delivery and an optimized manufacturing process exhibited
superior median overall survival of 10.2 months, compared to the
expected survival rate of six months in patients with recurrent
GBM. The median overall survival for all patients was eight
months.
- Intermediate/high pre-treatment
tumor T-cell levels that are indicative of a “hot” tumor
microenvironment (TME) correlated with a significant survival
benefit over negative/low pre-treatment tumor T-cell levels that
are indicative of a “cold” TME.
- Overall, all routes of delivery
(ICT, ICV and dual ICT + ICV) were well-tolerated at doses up to
200×106 CAR T-cells.
- Central nervous system (CNS)
increases in inflammatory cytokines, including IFNγ, CXCL9, and
CXCL10, were associated with CAR T-cell administration and
bioactivity.
Dr. Christine Brown, Heritage Provider Network
Professor in Immunotherapy, deputy director of the T-Cell
Therapeutics Research Laboratories at City of Hope, and lead author
on the publication, said, “These Phase 1 clinical trial results
represent a significant step forward in our understanding of the
potential of MB-101 CAR T-cell therapy to treat recurrent GBM, an
extremely aggressive tumor with very limited treatment options. One
of the main challenges for treating brain cancer is that
medications have difficulty crossing the blood-brain barrier. To
overcome that barrier, the trial delivered CAR T-cells directly
into the brain tumor and the cerebrospinal fluid, the fluid that
protects and surrounds the brain and spinal cord. Repetitive
locoregional administration of IL13Rα2-CAR T-cells was feasible and
well-tolerated with no dose limiting toxicities, even at the
highest dose level of 200 x 106 CAR T-cells per infusion. The
safety and promising therapy-related bioactivity data pave the way
for future studies of MB-101 and offer hope for a transformative
treatment approach. We look forward to continuing our work with
Mustang on this promising therapy.”
Manuel Litchman, M.D., President and Chief
Executive Officer of Mustang, said, “MB-101 has demonstrated
compelling therapeutic potential, including delivering
unprecedented complete responses in two high-grade glioma patients;
the first patient who achieved a complete response was published in
The New England Journal of Medicine. These two patients treated
solely with MB-101 both had high levels of intratumoral CD3+
T-cells pre-therapy (i.e., “hot” tumors) and achieved complete
responses lasting 7.5 and 66+ months, respectively. This trial has
led to several other studies using MB-101, including supporting our
upcoming novel combination clinical trial of MB-109 [MB-101
(IL-13Rα2 targeted CAR T-cell therapy) + MB-108 (HSV-1 oncolytic
virus)] to improve treatment of recurrent GBM and high-grade
astrocytoma. The combination leverages initial treatment with
MB-108 to reshape the tumor microenvironment and make
immunologically “cold” tumors “hot,” thereby potentially enabling
the MB-101 CAR T-cell therapy to achieve efficacy equivalent to
that seen in intrinsically “hot” tumors in this City of Hope Phase
1 trial.”
The data reported on 65 patients with recurrent
high-grade glioma, the majority being glioblastoma (GBM;
2 + recurrences); 58 patients were evaluable for disease response.
Primary endpoints were safety and feasibility, with secondary
endpoints measuring therapy-related cytokine dynamics, CAR T-cell
persistence and clinical outcomes. Patients were treated at one of
three dose schedules with three weekly infusions administered
without prior lymphodepleting chemotherapy and were evaluated one
week after the third cycle for dose limiting toxicities. Additional
infusions were allowed, and patients were followed for toxicities,
response, and survival until they progressed or required subsequent
therapy. This study evaluated five treatment arms: Arm 1,
intratumoral following biopsy (ICT Biopsy); Arm 2, intratumoral
following maximal surgical resection (ICT Resection); Arm 3,
intraventricular (ICV); and Arms 4 and 5, combined ICT and ICV
delivery (Dual ICT + ICV). ICV delivery (Arm 3) was added after
trial initiation based on clinical experience, in which IL13Rα2-CAR
T-cells that were administered ICV mediated a complete response in
a patient with multifocal recurrent GBM, and preclinical data
suggested ICV was more effective against multifocal tumors.
Subsequently, City of Hope transitioned to dual delivery combining
both ICV and ICT (Arms 4–5) – rather than continuing with ICV alone
– as preclinical data also suggested that intratumoral delivery was
more effective for defined unifocal tumors in comparison to
ICV-only delivery.
Weekly ICT and/or ICV administration of
IL13Rα2-CAR T-cells was well-tolerated, with clinically manageable
adverse events. No high-grade cytokine release syndrome or immune
effector cell-mediated neurotoxicity adverse events were observed,
and no dose limiting toxicities (DLTs) were noted during the 28-day
dose limiting toxicity period. The most common toxicities with
possible or higher attribution to CAR T-cells were fatigue,
headache, and hypertension. Grade 3 and above toxicities with
possible or higher attribution to CAR T-cells were seen in 35% of
patients, including two incidences of transient grade 4 cerebral
edema with possible attribution to CAR T-cells and one grade 3
encephalopathy and one grade 3 ataxia with probable attribution to
CAR T-cells.
A link to the Nature Medicine publication can be
found here.
Dr. Brown has a financial interest in Mustang and has previously
been a paid consultant for the company.
Additional information on the Phase 1 study can
be found on www.ClinicalTrials.gov using
identifier NCT02208362.
About Mustang BioMustang Bio,
Inc. is 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. Mustang aims to acquire rights to these
technologies by licensing or otherwise acquiring an ownership
interest, to fund research and development, and to outlicense or
bring the technologies to market. Mustang has partnered with top
medical institutions to advance the development of CAR-T therapies
across multiple cancers, as well as lentiviral gene therapies for
severe combined immunodeficiency. Mustang’s common stock is
registered under the Securities Exchange Act of 1934, as amended,
and Mustang files periodic reports with the U.S. Securities and
Exchange Commission (“SEC”). Mustang was founded by Fortress
Biotech, Inc. (Nasdaq: FBIO). For more information, visit
www.mustangbio.com.
Forward‐Looking StatementsThis
press release contains “forward-looking statements” within the
meaning of Section 27A of the Securities Act of 1933 and Section
21E of the Securities Exchange Act of 1934, each as amended. Such
statements, which are often indicated by terms such as
“anticipate,” “believe,” “could,” “estimate,” “expect,” “goal,”
“intend,” “look forward to,” “may,” “plan,” “potential,” “predict,”
“project,” “should,” “will,” “would” and similar expressions. The
Company’s forward-looking statements, include, but are not limited
to, any statements relating to our growth strategy and product
development programs, including the timing of and our ability to
make regulatory filings such as INDs and other applications and to
obtain regulatory approvals for our product candidates, statements
concerning the potential of therapies and product candidates and
any other statements that are not historical facts. Actual events
or results may differ materially from those described in this press
release due to a number of risks and uncertainties. Risks and
uncertainties include, among other things, risks related to the
satisfaction of the conditions necessary to transfer the lease of
the Company’s manufacturing facility and receive the contingent
payment in connection with the Company’s sale of its manufacturing
facility in the anticipated timeframe or at all; whether the
purchaser of the Company’s manufacturing facility is able to
successfully perform its obligation to produce the Company’s
products under the manufacturing services agreement on a timely
basis and to acceptable standards; disruption from the sale of the
Company’s manufacturing facility making it more difficult to
maintain business and operational relationships; negative effects
of the announcement or the consummation of the transaction on the
market price of the Company’s common stock; significant transaction
costs; the development stage of the Company’s primary product
candidates, our ability to obtain, perform under, and maintain
financing and strategic agreements and relationships; risks
relating to the results of research and development activities;
risks relating to the timing of starting and completing clinical
trials; uncertainties relating to preclinical and clinical testing;
our dependence on third-party suppliers; our ability to attract,
integrate and retain key personnel; the early stage of products
under development; our need for substantial additional funds;
government regulation; patent and intellectual property matters;
competition; as well as other risks described in Part I, Item 1A,
“Risk Factors,” in our Annual Report on Form 10-K filed on March
30, 2023, subsequent Reports on Form 10-Q, and our other filings we
make with the SEC. We expressly disclaim any obligation or
undertaking to release publicly any updates or revisions to any
forward-looking statements contained herein to reflect any change
in our expectations or any changes in events, conditions or
circumstances on which any such statement is based, except as
required by law, and we claim the protection of the safe harbor for
forward-looking statements contained in the Private Securities
Litigation Reform Act of 1995.
Company Contacts:Jaclyn Jaffe
and Nicole McCloskeyMustang Bio, Inc.(781)
652-4500ir@mustangbio.com
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