Medical, Industry Outlook
Globenewswire | August 17, 2023
Mustang Bio Inc. 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 the first data from the indolent lymphoma cohort of the Company’s ongoing multicenter Phase 1/2 clinical trial evaluating 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”), demonstrating clinical responses as well as safety and efficacy consistent with the ongoing Phase 1/2 clinical trial taking place at Fred Hutchinson Cancer Center (“Fred Hutch”).
Initial data were presented by Mazyar Shadman, M.D., M.P.H., Study Chair, Associate Professor and physician at Fred Hutch and University of Washington, at the 5th International Workshop on CAR-T and Immunotherapies (“iwCAR-T”).
Manuel Litchman, M.D., President and Chief Executive Officer of Mustang, said, “We are encouraged that the first data from the multicenter trial of our lead candidate, MB-106, show clinical responses and that the trial is on track to achieve results consistent with those from the ongoing trial taking place at Fred Hutch. Overall, MB-106 continues to exhibit high efficacy and a favorable safety profile compared to currently approved autologous CAR-Ts. We expect to provide an additional update on dose escalation and report response data at a major medical meeting later this year.”
The multicenter study data show clinical responses in four of four patients with relapsed or refractory indolent NHL at the starting dose of 3.3 x 106 CAR-T cells/kg, a dose comparable to that employed for the majority of the indolent lymphoma patients in the Fred Hutch trial. The multicenter data also show persistence of CAR-T cells at 6+ months and favorable safety data with only Grade 1 cytokine release syndrome (“CRS”) reported to date. Two patients with follicular lymphoma had complete response (“CR”) by both PET-CT and bone marrow, one of whom had been previously treated with a CD19-directed CAR-T. A third patient, with a diagnosis of Waldenstrom macroglobulinemia (“WM”), who had nine prior treatments and high disease burden, achieved complete metabolic response by PET-CT, morphologic clearance of lymphoma in bone marrow, and resolution of the IgM monoclonal protein. The fourth patient, with a diagnosis of hairy cell leukemia variant, who had been heavily transfusion dependent, continues to have stable disease with decreased disease in his bone marrow and achieved complete transfusion independence, which is ongoing at 6+ months.
“MB-106 continues to show potential as an immunotherapy option for patients with a wide range of hematologic malignancies, including patients previously treated with CD19-directed CAR-T cell therapy,” said Mazyar Shadman, M.D., M.P.H., who holds the Innovators Network Endowed Chair at Fred Hutch and is the Study Chair, as well as Associate Professor and physician at Fred Hutch and University of Washington. “We are excited that the first data from the expanded evaluation of MB-106 are similar in safety as what we’ve seen to date in the ongoing Phase 1/2 clinical trial at Fred Hutch. Additionally, the data from the ongoing clinical trial at Fred Hutch continue to demonstrate a high rate of complete and durable responses.”
Dr. Shadman also presented data from the ongoing Fred Hutch Phase 1/2 clinical trial, specific to two B-NHL cohorts, follicular lymphoma (“FL”) and WM. In the FL data cohort (n=20), an overall response rate (“ORR”) of 95% was seen, of which 80% of patients experienced a CR, and 15% had a partial response. The CR patients include a patient who was previously treated with a CD19-directed CAR-T cell therapy. Of the six patients who experienced CRS, only one had Grade 2. Ten patients continue to experience CR for more than 10 months, four patients have experienced CR for more than two years (all ongoing), and the first patient enrolled has sustained CR for more than 3 years. In the WM cohort (n=6), all of whom had received prior Bruton tyrosine kinase inhibitor, two patients experienced CR, one of whom continues to be in CR at more than 22 months. No patients experienced CRS or immune effector cell-associated neurotoxicity syndrome over Grade 2. None of the six WM patients have needed to start new therapy for their disease.
As previously reported, 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 and received Orphan Drug Designation from the U.S. Food and Drug Administration (“FDA”). There is currently no FDA-approved CAR-T cell therapy for WM, and the first patient in the pivotal Phase 2 WM trial is expected to be treated in mid-2024, which could enable top-line data as early as mid-2026. By the end of 2023, we anticipate confirming this strategy at an end-of-Phase 1 meeting with the US Food and Drug Administration (FDA). Furthermore, Mustang anticipates requesting regenerative medicine advanced therapy (RMAT) designation for WM from the FDA in 2024. Finally, 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.
About Mustang’s Multicenter MB-106 Phase 1/2 Clinical Trial
The five-center Phase 1/2 clinical trial is a three-arm study targeting CLL and B-NHL, including FL, diffuse large B-cell lymphoma and mantle cell lymphoma. We anticipate adding a sixth center by the end of 2023. The Mustang-sponsored multicenter clinical trial is using the same lentiviral vector as the Fred Hutch-sponsored single-center trial. Included in the eligibility criteria are patients who have relapsed after treatment with CD19 CAR-T cell therapy. Additionally, the FL arm will evaluate other indolent histologies including Waldenstrom macroglobulinemia, a rare type of B-NHL for which the U.S. Food and Drug Administration granted MB-106 Orphan Drug Designation. Patients will be enrolled in one of three arms, based on their primary diagnosis; escalating MB-106 dose levels will be tested independently in each arm using a 3+3 design.
A total of up to 18 patients are anticipated to be treated in each Phase 1 arm, including six patients at the maximum tolerated dose in each independent arm. Safety of each dose level will be reviewed for each arm until the maximum tolerated dose has been reached and the recommended Phase 2 dose (“RP2D”) has been established for each arm. An assessment of the safety and tolerability of the dose will be made by the Safety Review Committee based on the data from the 28-day dose-limiting toxicity observation period.
In Phase 2, specific arms of relapsed or refractory CD20-positive B-cell hematologic malignancies will be treated with MB-106 at the respective RP2D for each arm. The two top priorities are WM and diffuse large B-cell lymphoma (DLBCL) relapsed from prior CD19 CAR-T therapy. Each arm will initially include up to 20 patients. Based on the results of the interim analysis, up to an additional 51 patients may be added to each of the arms.
About MB-106 (CD20-targeted autologous CAR-T Cell Therapy)
CD20 is a membrane-embedded surface molecule which plays a role in the differentiation of B-cells into plasma cells. The CAR-T was developed by Mustang’s research collaborator, Fred Hutch, in the laboratories of the late Oliver Press, M.D., Ph.D., and Brian Till, M.D., Associate Professor in the Clinical Research Division at Fred Hutch, and was exclusively licensed to Mustang in 2017. The lentiviral vector drug substance used to transduce patients’ cells to create the MB-106 drug product produced at Fred Hutch has been optimized as a third-generation CAR derived from a fully human antibody. MB-106 is currently in a Phase 1/2 open-label, dose-escalation trial at Fred Hutch in patients with B-NHLs and CLL. The same lentiviral vector drug substance produced at Fred Hutch is used to transduce patients’ cells to create the MB-106 drug product produced at Mustang Bio’s Worcester, MA, cell processing facility for administration in the multicenter Phase 1/2 clinical trial under Mustang Bio’s IND. It should be noted that Mustang Bio has introduced minor improvements to its cell processing to facilitate eventual commercial launch of the product. In addition, prior to commercial launch, Mustang Bio will replace the Fred Hutch lentiviral vector drug substance with vector produced at a commercial manufacturer. Additional information on the trials can be found at http://www.clinicaltrials.gov using the identifier NCT05360238 for the multicenter trial and NCT03277729 for the ongoing trial at Fred Hutch. On May 18, 2023 Mustang Bio entered into an Asset Purchase Agreement, as amended by the First Amendment, dated as of June 29, 2023 and a Second Amendment, dated as of July 28, 2023 pursuant to which it agreed to sell its assets primarily pertaining to the manufacturing and production of cell and gene therapies located at its cell processing facility in Worcester, MA; and, subject to the satisfaction of certain conditions, its leasehold interest in that facility. Concurrent with the Second Amendment, Mustang closed the transaction under the terms of the amended asset purchase agreement and entered into manufacturing services agreements with the purchaser to provide for the continued production of the MB-106 drug product. For additional information, please refer to the Form 8-Ks filed by Mustang Bio with the U.S. Securities and Exchange Commission (“SEC”) on May 22, 2023, June 30, 2023 and July 31, 2023.
About Mustang Bio
Mustang 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.
Cell and Gene Therapy
prnewswire | September 14, 2023
Ceres Nanosciences, a global leader in developing wastewater testing methods based on its Nanotrap® technology, and Ginkgo Bioworks which is building the leading platform for cell programming and biosecurity, today announced that they are partnering to bring pathogen monitoring capabilities to laboratories around the world. Pathogen monitoring and analysis capabilities, including in wastewater, are designed to help public health institutions address regional biosecurity challenges.
Supported by the NIH RADx Initiative, Ceres developed their Nanotrap technology for robust, sensitive, and time-saving methods to detect a wide range of pathogens in wastewater samples and has deployed those methods to a network of testing sites in the United States. These sites provide wastewater testing services nationwide to deliver valuable public health data, such as information about the relative abundance of COVID-19 variant groups over time in a community's wastewater, to the CDC's National Wastewater Surveillance System and to state, local, and Tribal decision makers.
Recently, Concentric by Ginkgo, the biosecurity unit of Ginkgo Bioworks, as part of a CDC program, demonstrated in a study with partners from XPresCheck and Louisiana State University that coupling Ceres' aircraft wastewater testing methods with Concentric's analysis can enable early detection of variants of SARS-CoV-2. San Francisco International Airport was the first airport to announce that it will continuously monitor airplane wastewater samples as part of a CDC program operated by Concentric and XpresCheck.
Under the partnership between Ceres and Concentric, labs in countries where Concentric has biosecurity programs receive on-site training and the materials needed to implement the standardized and proven wastewater testing workflow from Ceres. Labs also receive biosecurity tools and data infrastructure to leverage automation, data analysis, bioinformatics capabilities, and other critical genomic sequencing technologies.
Together, Ceres and Concentric have set up labs in the Middle East and Africa through this collaboration, offering a cutting-edge approach to biosurveillance technologies and capacity building for labs around the world that are part of Concentric's global pathogen monitoring network.
"Under our NIH RADx Initiative, we demonstrated that we can quickly stand up improved wastewater testing capabilities for labs that are experts or novices in the space," said Robbie Barbero, Chief Business Officer at Ceres Nanosciences. "We are delighted now to be partnering with a global leader like Concentric to build a robust public health framework worldwide."
"Ceres Nanosciences has been a terrific partner in developing effective and innovative methods for identifying pathogens in wastewater," said Matt McKnight, General Manager, Biosecurity at Ginkgo Bioworks. "By combining their laboratory expertise with our global footprint, we are building a robust global biological radar to prevent, detect, and respond to biological threats."
About Ceres Nanosciences, Inc.
Ceres Nanosciences is a privately held company, located in Northern Virginia, focused on incorporating its proprietary Nanotrap® particle technology into a range of diagnostic and research use products and workflows. Nanotrap particles capture, concentrate, and preserve low abundance analytes from biological samples, enabling early and accurate detection of diseases. The Nanotrap particle technology was developed with support from the National Institutes of Health, the Defense Advanced Research Projects Agency, the Bill and Melinda Gates Foundation, Schmidt Futures, the Defense Threat Reduction Agency, the Centers for Disease Control and Prevention, and the Commonwealth of Virginia.
About Ginkgo Bioworks
Ginkgo Bioworks is the leading horizontal platform for cell programming, providing flexible, end-to-end services that solve challenges for organizations across diverse markets, from food and agriculture to pharmaceuticals to industrial and specialty chemicals. Ginkgo's biosecurity and public health unit, Concentric by Ginkgo, is building global infrastructure for biosecurity to empower governments, communities, and public health leaders to prevent, detect and respond to a wide variety of biological threats.
Businesswire | July 21, 2023
Sangamo Therapeutics, Inc. a clinical-stage genomic medicine company and Chroma Medicine, Inc. a genomic medicine company pioneering single-dose epigenetic editing therapeutics, today announced they have entered into a research evaluation, option and license agreement to develop epigenetic medicines leveraging zinc finger proteins (ZFPs) for sequence-specific DNA recognition. Over the course of two decades, Sangamo has built and validated the world’s largest library of ZFPs, deploying them to address numerous therapeutically relevant targets. Advancing the transformative potential of epigenetic editing, Chroma is expanding the versatility of its platform by leveraging Sangamo’s ZFPs. Following a research evaluation period, Chroma has the option to license the ZFPs for potential worldwide development and commercialization of epigenetic medicines for certain therapeutic targets.
“Sangamo is the world leader in zinc finger protein genomic engineering, and we are very proud of the range and depth of our capabilities in this area,” said Jason Fontenot, Ph.D., Chief Scientific Officer at Sangamo. “We believe our ability to rapidly design and engineer highly potent and specific ZFPs can provide unique and highly valuable capability beyond what is available with competing technologies. We are constantly seeking to deploy our technology with partners outside of our core neurology focus area and are very happy to explore combining our ZF technology with Chroma’s unique capabilities. We believe that this work will further validate the importance of zinc fingers as an ideal platform to support epigenetic editing.”
Under the terms of the agreement, Chroma will evaluate novel Sangamo ZFPs for specified collaboration targets outside of the central nervous system in exchange for an upfront technology access payment. If Chroma exercises its option for any or all targets, Sangamo would be eligible to receive an option exercise payment, in addition to potential development and commercial milestone payments, as well as royalties on any Chroma products incorporating the licensed ZFPs. Chroma will lead and fund all research, development, manufacture, and commercialization of products incorporating the licensed Sangamo ZFPs.
“As a leader in epigenetic editing, Chroma has advanced and optimized our platform, showing highly efficient, specific, and durable gene silencing in vivo and the ability to accomplish multiplex epigenetic editing without induction of indels or chromosomal rearrangements,” said Vic Myer, Ph.D., President and Chief Scientific Officer of Chroma. “Leveraging Sangamo’s leading zinc finger protein engineering capabilities expands our platform optionality, further positioning Chroma to progress a broad portfolio of epigenetic editing therapeutics that spans several indications.”
About Sangamo Therapeutics
Sangamo Therapeutics is a clinical-stage biopharmaceutical company with a robust genomic medicines pipeline. Using ground-breaking science, including our proprietary zinc finger genome engineering technology and manufacturing expertise, Sangamo aims to create new genomic medicines for patients suffering from diseases for which existing treatment options are inadequate or currently don’t exist.
About Chroma Medicine, Inc.
Chroma Medicine is a biotechnology company pioneering a new class of genomic medicines that harness epigenetics, nature’s innate mechanism for gene regulation, to deliver precise, programmable single-dose therapeutics while preserving genomic integrity. The company was founded by the world’s foremost experts in genomic research and is led by a veteran team of industry leaders and scientists with deep experience in genomic medicine, drug discovery, and development.