Advancement in Genomics Accelerating its Penetration into Precision Health

Kutubkhan Bohari | June 22, 2022 | 535 views | Read Time : 01:30 min

Advance_ment_in

Genomics is an interdisciplinary field of biology emphasizing the structure, editing, evolution, function, and mapping of genomes. It is creating deeper inroads across the precision health domain with the increasing introduction of advanced technologies such as quantum simulation, next-generation sequencing (NGS), and precise genome manipulation.

As precision health focuses on providing the proper intervention to the right patient at the right time, genomics increasingly finds applications in human and pathogen genome sequencing in clinical and research spaces.

Rising Hereditary Diseases Burden Paving the Way for Genomics in Precision Health

In the last few years, a significant surge in the prevalence of diseases and ailments such as diabetes, obesity, baldness, and others has been witnessed across the globe. A history of family members with chronic diseases, such as cancer, diabetes, high blood pressure, hearing issues, and heart disease, can sometimes continue into the next generation.

Hence, the study of genes is extensively being conducted for predicting health risks and early treatment of these diseases. It also finds use in CRISPR-based diagnostics and the preparation of precision medication for the individual.
In addition, ongoing advancements in genomics are making it possible to identify different genetic traits that persuade people to more widespread diseases and health problems.


The Emergence of Genomics Improves Disease Understanding

Genomics refers to the study of the complete genetic makeup of a cell or organism. Increasing scientific research in the area substantially contributes to increasing knowledge about the human genome and assists in improving the ability to understand disease etiology, risk, diagnosis, treatment, and prevention. On account of these improvements, innovative genomic technologies and tools are being developed to enable better precision health not only for the individual but for various regional populations as well.


The Way Forward

With growing preference for personalized medicine and an increasing need for more accurate pathogen detection and diagnostics, genomics is gaining huge popularity across the precision health domain.
Also, increasing research activities for developing novel high-precision therapeutics and rising importance of gene study in the prevention, diagnosis, and management of infectious and genetic diseases will further pave the way for genomics in the forthcoming years.

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Mustang Bio Announces Strategic Manufacturing Partnership and Portfolio Updates

Globenewswire | May 19, 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 a strategic update, including anticipated milestones for 2023. 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. 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 to develop MB-106 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 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 hematologic cancers, solid tumors 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.

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Cellectis Presents Clinical Data on AMELI-01 and Preclinical Data on Multiplex Engineering for Superior Generation of CAR T-cells at ASGCT 2023

Globenewswire | May 18, 2023

Cellectis a clinical-stage biotechnology company using its pioneering gene-editing platform to develop life-saving cell and gene therapies, today presents clinical data on its Phase 1 AMELI-01 clinical trial (evaluating UCART123) that were unveiled in an oral presentation at the 64th American Society of Hematology (ASH) annual meeting, as well as preclinical data on multiplex engineering for superior generation of CAR T-cells, at the American Society of Gene and Cell Therapy (ASGCT) 2023 Annual Meeting. Preliminary Clinical Data from the AMELI-01 Study Presented at ASH 2022 AMELI-01 is a Phase 1 open-label dose-escalation trial evaluating the safety, tolerability, expansion and preliminary activity of UCART123 given at escalating dose levels after lymphodepletion (LD) with either fludarabine and cyclophosphamide (FC) or FC with alemtuzumab (FCA) in patients with relapsed or refractory acute myeloid leukemia (r/r AML). The oral presentation reviewed preliminary data from patients who received UCART123 at one of the following dose levels: dose level 1 (DL1) 2.5x105 cells/kg; dose level 2 (DL2) 6.25x105 cells/kg; intermediate dose level 2 (DL2i) 1.5x106 cells/kg; or dose level 3 (DL3) 3.30x106 cells/kg after lymphodepletion with FC ([n=8], DL1 – DL3) or FCA ([n=9], DL2 & DL2i). Preliminary Safety Data The FCA LD regimen resulted in robust lymphodepletion for greater than 28 days in all patients. Seven out of nine patients demonstrated UCART123 expansion, with maximum concentration (Cmax) ranging from 13,177 to 330,530 copies/μg DNA, an almost nine-fold increase compared with FC LD, and a significant increase in area under the curve (AUC) (0-28 days) (p=0.04; FC 10.2 vs. FCA 34.9). Cytokine release syndrome (CRS) occurred in eight patients in the FC arm and nine patients in the FCA arm. In the FC arm, one patient experienced Grade 3 immune effector cell-associated neurotoxicity syndrome (ICANS) and two patients experienced Grade 4 protocol-defined dose limiting toxicities (DLTs) secondary to CRS. In the FCA arm, two patients experienced Grade 5 DLTs secondary to CRS. Patient Enrollment in a 2-Dose Regimen Arm Overall, these preliminary data support the continued administration of UCART123 after FCA lymphodepletion in patients with r/r AML. Based on observed UCART123 expansion patterns and cytokine profiles, pursuant to an amended protocol, a second dose of UCART123 is given after 10-14 days to allow for additional UCART123 expansion and clinical activity without the use of additional lymphodepletion. The UCART123 cell expansion from the second dose of UCART123, in the setting of reduced disease burden, is expected to be safe and allow for clearance of residual disease. About Cellectis Cellectis is a clinical-stage biotechnology company using its pioneering gene-editing platform to develop life-saving cell and gene therapies. Cellectis utilizes an allogeneic approach for CAR-T immunotherapies in oncology, pioneering the concept of off-the-shelf and ready-to-use gene-edited CAR T-cells to treat cancer patients, and a platform to make therapeutic gene editing in hemopoietic stem cells for various diseases. As a clinical-stage biopharmaceutical company with over 23 years of experience and expertise in gene editing, Cellectis is developing life-changing product candidates utilizing TALEN®, its gene editing technology, and PulseAgile, its pioneering electroporation system to harness the power of the immune system in order to treat diseases with unmet medical needs. Cellectis’ headquarters are in Paris, France, with locations in New York, New York and Raleigh, North Carolina. Cellectis is listed on the Nasdaq Global Market and on Euronext Growth .

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RESEARCH, DIAGNOSTICS

Xilio Therapeutics Releases Preliminary Results of XTX101 Phase 1 Trial

Globenewswire | May 26, 2023

Xilio Therapeutics, Inc. (Nasdaq: XLO), a clinical-stage biotechnology company discovering and developing tumor-activated immuno-oncology therapies for people living with cancer, today announced preliminary data from its Phase 1 clinical trial evaluating XTX101, an investigational tumor-activated, Fc-enhanced anti-CTLA-4, in patients with advanced solid tumors. “We are encouraged by the preliminary data from the Phase 1 trial for XTX101 showing evidence of tumor-selective activation,” said Martin Huber, M.D., president and head of research and development at Xilio. “Following treatment with XTX101 monotherapy at the recommended Phase 2 dose of 150 mg once every six weeks, we observed a partial response in a patient with PD-L1 negative advanced non-small cell lung cancer. Importantly, this anti-tumor activity occurred in the absence of meaningful observed activation of the immune system in the periphery, suggesting tumor-selective activation of XTX101. Based on these Phase 1 data, we plan to explore opportunities to evaluate XTX101 in combination with an anti-PD-(L)1 in historically immunotherapy-resistant tumor types.” Data from the Ongoing Phase 1 Clinical Trial for XTX101 As of a data cutoff date of May 2, 2023, 25 patients had been treated with XTX101, including dose levels ranging from 7 mg to 180 mg administered once every three weeks (Q3W) and one dose level at 150 mg administered once every six weeks (Q6W). Of these patients, 20 patients were dosed in monotherapy dose-escalation (Part 1A) and five patients were dosed in monotherapy dose-expansion (Part 1B). Patients had a wide range of advanced and treatment-refractory solid tumors, including colorectal cancer (CRC), non-small cell lung cancer (NSCLC) and pancreatic cancer. In addition, 76% of patients had been previously treated with at least three prior lines of anti-cancer therapy, and 44% had been previously treated with at least one immuno-oncology (I-O) agent. As of the data cutoff date, three patients were continuing on treatment with XTX101, and 22 patients had discontinued treatment with XTX101. Preliminary Safety Data A recommended Phase 2 dose (RP2D) and schedule of 150 mg Q6W was determined based on the favorable preliminary safety, pharmacokinetic (PK) and pharmacodynamic (PD) data for XTX101. At the RP2D, no dose-limiting toxicities were observed, and there was no reported evidence of immune-related endocrine or skin adverse events (AEs) that are commonly associated with systemically active anti-CTLA-4 agents. In addition, evidence of effective masking of XTX101 was demonstrated by low levels of unmasked drug detected in peripheral circulation, and XTX101 achieved target PK exposure at the RP2D, reaching the targeted area under the curve (AUC) and peak concentration (Cmax). As of the data cutoff date: Across all dosing levels and dosing intervals, no Grade 4 or Grade 5 treatment-related AEs were reported by investigators. Among seven patients who received XTX101 administered at the RP2D of 150 mg on a Q6W dosing schedule, the most common treatment-related AEs (≥10% incidence) of any grade reported by investigators were diarrhea (14%), fatigue (14%) and decreased appetite (14%). In these patients, no treatment-related colitis or infusion related reaction of any grade was observed. Investigators reported only one Grade 3 treatment-related AE of diarrhea, which occurred after two doses and resolved after five days without steroid use. This patient tolerated two additional doses of XTX101 after dose reduction to 75 mg Q6W without any symptom recurrence. At the RP2D of 150 mg Q6W, this was the only patient with a dose reduction due to an AE, and no patients discontinued treatment due to a treatment-related AE. Among 18 patients who received XTX101 administered on a Q3W dosing schedule, the most common treatment-related AEs (≥10% incidence) of any grade reported by investigators were diarrhea (28%), colitis (28%), infusion related reaction (28%), nausea (17%), vomiting (17%) and abdominal pain (11%). Of these, investigators reported the following Grade 3 treatment-related AEs: diarrhea (6%), colitis (22%) and infusion related reaction (17%). Infusion related reactions were associated with antidrug antibodies. Across all dose levels administered Q3W, two patients had dose reductions due to AEs, and four patients discontinued treatment due to an infusion related reaction. Preliminary Anti-Tumor Activity A partial response was observed at nine weeks in one patient with advanced PD-L1 negative NSCLC with hepatic metastases treated with XTX101 at the 150 mg Q6W dose level and confirmed after the data cutoff date at week 27. The only treatment-related AE reported for this patient was Grade 1 fatigue. In addition, PD markers for anti-CTLA-4 reported for this patient showed minimal immune activation in peripheral circulation, demonstrating evidence of tumor-selective activation of XTX101. The patient is currently continuing on treatment with XTX101. Clinical Development Plan for XTX101 Enrollment in monotherapy dose-expansion (Part 1B) of the Phase 1 trial is currently ongoing, with the goal of further characterizing the safety, PK and PD of XTX101 at the RP2D of 150 mg Q6W. In addition, mandatory tumor biopsies will be obtained from patients in Part 1B to examine intra-tumoral PK and PD for XTX101. Xilio plans to continue to explore strategic opportunities to advance XTX101 with a partner beyond the current Phase 1 monotherapy cohorts, including in potential Phase 1 dose escalation evaluating XTX101 in combination with a PD-(L)1 and in a potential Phase 2 trial evaluating XTX101 in combination with a PD-(L)1 in patients with microsatellite stable CRC. About XTX101 (anti-CTLA-4) and the Phase 1 Clinical Trial XTX101 is an investigational tumor-activated, Fc-enhanced anti-CTLA-4 monoclonal antibody designed to deplete regulatory T cells when activated (unmasked) in the tumor microenvironment (TME). The Phase 1 clinical trial is a first-in-human, multi-center, open-label trial designed to evaluate the safety and tolerability of XTX101 for the treatment of patients with advanced solid tumors. The primary outcome measures were the incidence of dose-limiting toxicities (DLTs) and the incidence of treatment-related adverse events, and changes in clinical laboratory abnormalities. Please refer to NCT04896697 on www.clinicaltrials.gov for additional details. About Xilio Therapeutics Xilio Therapeutics is a clinical-stage biotechnology company discovering and developing tumor-activated immuno-oncology (I-O) therapies with the goal of significantly improving outcomes for people living with cancer without the systemic side effects of current I-O treatments. The company is using its proprietary geographically precise solutions (GPS) platform to build a pipeline of novel, tumor-activated molecules, including cytokines and other biologics, which are designed to optimize their therapeutic index and localize anti-tumor activity within the tumor microenvironment. Xilio is currently advancing multiple programs for tumor-activated I-O treatments in clinical development, as well as programs in preclinical development. Learn more by visiting www.xiliotx.com and follow us on Twitter (@xiliotx) and LinkedIn (Xilio Therapeutics, Inc.).

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INDUSTRY OUTLOOK

Mustang Bio Announces Strategic Manufacturing Partnership and Portfolio Updates

Globenewswire | May 19, 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 a strategic update, including anticipated milestones for 2023. 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. 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 to develop MB-106 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 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 hematologic cancers, solid tumors 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.

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MEDICAL

Cellectis Presents Clinical Data on AMELI-01 and Preclinical Data on Multiplex Engineering for Superior Generation of CAR T-cells at ASGCT 2023

Globenewswire | May 18, 2023

Cellectis a clinical-stage biotechnology company using its pioneering gene-editing platform to develop life-saving cell and gene therapies, today presents clinical data on its Phase 1 AMELI-01 clinical trial (evaluating UCART123) that were unveiled in an oral presentation at the 64th American Society of Hematology (ASH) annual meeting, as well as preclinical data on multiplex engineering for superior generation of CAR T-cells, at the American Society of Gene and Cell Therapy (ASGCT) 2023 Annual Meeting. Preliminary Clinical Data from the AMELI-01 Study Presented at ASH 2022 AMELI-01 is a Phase 1 open-label dose-escalation trial evaluating the safety, tolerability, expansion and preliminary activity of UCART123 given at escalating dose levels after lymphodepletion (LD) with either fludarabine and cyclophosphamide (FC) or FC with alemtuzumab (FCA) in patients with relapsed or refractory acute myeloid leukemia (r/r AML). The oral presentation reviewed preliminary data from patients who received UCART123 at one of the following dose levels: dose level 1 (DL1) 2.5x105 cells/kg; dose level 2 (DL2) 6.25x105 cells/kg; intermediate dose level 2 (DL2i) 1.5x106 cells/kg; or dose level 3 (DL3) 3.30x106 cells/kg after lymphodepletion with FC ([n=8], DL1 – DL3) or FCA ([n=9], DL2 & DL2i). Preliminary Safety Data The FCA LD regimen resulted in robust lymphodepletion for greater than 28 days in all patients. Seven out of nine patients demonstrated UCART123 expansion, with maximum concentration (Cmax) ranging from 13,177 to 330,530 copies/μg DNA, an almost nine-fold increase compared with FC LD, and a significant increase in area under the curve (AUC) (0-28 days) (p=0.04; FC 10.2 vs. FCA 34.9). Cytokine release syndrome (CRS) occurred in eight patients in the FC arm and nine patients in the FCA arm. In the FC arm, one patient experienced Grade 3 immune effector cell-associated neurotoxicity syndrome (ICANS) and two patients experienced Grade 4 protocol-defined dose limiting toxicities (DLTs) secondary to CRS. In the FCA arm, two patients experienced Grade 5 DLTs secondary to CRS. Patient Enrollment in a 2-Dose Regimen Arm Overall, these preliminary data support the continued administration of UCART123 after FCA lymphodepletion in patients with r/r AML. Based on observed UCART123 expansion patterns and cytokine profiles, pursuant to an amended protocol, a second dose of UCART123 is given after 10-14 days to allow for additional UCART123 expansion and clinical activity without the use of additional lymphodepletion. The UCART123 cell expansion from the second dose of UCART123, in the setting of reduced disease burden, is expected to be safe and allow for clearance of residual disease. About Cellectis Cellectis is a clinical-stage biotechnology company using its pioneering gene-editing platform to develop life-saving cell and gene therapies. Cellectis utilizes an allogeneic approach for CAR-T immunotherapies in oncology, pioneering the concept of off-the-shelf and ready-to-use gene-edited CAR T-cells to treat cancer patients, and a platform to make therapeutic gene editing in hemopoietic stem cells for various diseases. As a clinical-stage biopharmaceutical company with over 23 years of experience and expertise in gene editing, Cellectis is developing life-changing product candidates utilizing TALEN®, its gene editing technology, and PulseAgile, its pioneering electroporation system to harness the power of the immune system in order to treat diseases with unmet medical needs. Cellectis’ headquarters are in Paris, France, with locations in New York, New York and Raleigh, North Carolina. Cellectis is listed on the Nasdaq Global Market and on Euronext Growth .

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RESEARCH, DIAGNOSTICS

Xilio Therapeutics Releases Preliminary Results of XTX101 Phase 1 Trial

Globenewswire | May 26, 2023

Xilio Therapeutics, Inc. (Nasdaq: XLO), a clinical-stage biotechnology company discovering and developing tumor-activated immuno-oncology therapies for people living with cancer, today announced preliminary data from its Phase 1 clinical trial evaluating XTX101, an investigational tumor-activated, Fc-enhanced anti-CTLA-4, in patients with advanced solid tumors. “We are encouraged by the preliminary data from the Phase 1 trial for XTX101 showing evidence of tumor-selective activation,” said Martin Huber, M.D., president and head of research and development at Xilio. “Following treatment with XTX101 monotherapy at the recommended Phase 2 dose of 150 mg once every six weeks, we observed a partial response in a patient with PD-L1 negative advanced non-small cell lung cancer. Importantly, this anti-tumor activity occurred in the absence of meaningful observed activation of the immune system in the periphery, suggesting tumor-selective activation of XTX101. Based on these Phase 1 data, we plan to explore opportunities to evaluate XTX101 in combination with an anti-PD-(L)1 in historically immunotherapy-resistant tumor types.” Data from the Ongoing Phase 1 Clinical Trial for XTX101 As of a data cutoff date of May 2, 2023, 25 patients had been treated with XTX101, including dose levels ranging from 7 mg to 180 mg administered once every three weeks (Q3W) and one dose level at 150 mg administered once every six weeks (Q6W). Of these patients, 20 patients were dosed in monotherapy dose-escalation (Part 1A) and five patients were dosed in monotherapy dose-expansion (Part 1B). Patients had a wide range of advanced and treatment-refractory solid tumors, including colorectal cancer (CRC), non-small cell lung cancer (NSCLC) and pancreatic cancer. In addition, 76% of patients had been previously treated with at least three prior lines of anti-cancer therapy, and 44% had been previously treated with at least one immuno-oncology (I-O) agent. As of the data cutoff date, three patients were continuing on treatment with XTX101, and 22 patients had discontinued treatment with XTX101. Preliminary Safety Data A recommended Phase 2 dose (RP2D) and schedule of 150 mg Q6W was determined based on the favorable preliminary safety, pharmacokinetic (PK) and pharmacodynamic (PD) data for XTX101. At the RP2D, no dose-limiting toxicities were observed, and there was no reported evidence of immune-related endocrine or skin adverse events (AEs) that are commonly associated with systemically active anti-CTLA-4 agents. In addition, evidence of effective masking of XTX101 was demonstrated by low levels of unmasked drug detected in peripheral circulation, and XTX101 achieved target PK exposure at the RP2D, reaching the targeted area under the curve (AUC) and peak concentration (Cmax). As of the data cutoff date: Across all dosing levels and dosing intervals, no Grade 4 or Grade 5 treatment-related AEs were reported by investigators. Among seven patients who received XTX101 administered at the RP2D of 150 mg on a Q6W dosing schedule, the most common treatment-related AEs (≥10% incidence) of any grade reported by investigators were diarrhea (14%), fatigue (14%) and decreased appetite (14%). In these patients, no treatment-related colitis or infusion related reaction of any grade was observed. Investigators reported only one Grade 3 treatment-related AE of diarrhea, which occurred after two doses and resolved after five days without steroid use. This patient tolerated two additional doses of XTX101 after dose reduction to 75 mg Q6W without any symptom recurrence. At the RP2D of 150 mg Q6W, this was the only patient with a dose reduction due to an AE, and no patients discontinued treatment due to a treatment-related AE. Among 18 patients who received XTX101 administered on a Q3W dosing schedule, the most common treatment-related AEs (≥10% incidence) of any grade reported by investigators were diarrhea (28%), colitis (28%), infusion related reaction (28%), nausea (17%), vomiting (17%) and abdominal pain (11%). Of these, investigators reported the following Grade 3 treatment-related AEs: diarrhea (6%), colitis (22%) and infusion related reaction (17%). Infusion related reactions were associated with antidrug antibodies. Across all dose levels administered Q3W, two patients had dose reductions due to AEs, and four patients discontinued treatment due to an infusion related reaction. Preliminary Anti-Tumor Activity A partial response was observed at nine weeks in one patient with advanced PD-L1 negative NSCLC with hepatic metastases treated with XTX101 at the 150 mg Q6W dose level and confirmed after the data cutoff date at week 27. The only treatment-related AE reported for this patient was Grade 1 fatigue. In addition, PD markers for anti-CTLA-4 reported for this patient showed minimal immune activation in peripheral circulation, demonstrating evidence of tumor-selective activation of XTX101. The patient is currently continuing on treatment with XTX101. Clinical Development Plan for XTX101 Enrollment in monotherapy dose-expansion (Part 1B) of the Phase 1 trial is currently ongoing, with the goal of further characterizing the safety, PK and PD of XTX101 at the RP2D of 150 mg Q6W. In addition, mandatory tumor biopsies will be obtained from patients in Part 1B to examine intra-tumoral PK and PD for XTX101. Xilio plans to continue to explore strategic opportunities to advance XTX101 with a partner beyond the current Phase 1 monotherapy cohorts, including in potential Phase 1 dose escalation evaluating XTX101 in combination with a PD-(L)1 and in a potential Phase 2 trial evaluating XTX101 in combination with a PD-(L)1 in patients with microsatellite stable CRC. About XTX101 (anti-CTLA-4) and the Phase 1 Clinical Trial XTX101 is an investigational tumor-activated, Fc-enhanced anti-CTLA-4 monoclonal antibody designed to deplete regulatory T cells when activated (unmasked) in the tumor microenvironment (TME). The Phase 1 clinical trial is a first-in-human, multi-center, open-label trial designed to evaluate the safety and tolerability of XTX101 for the treatment of patients with advanced solid tumors. The primary outcome measures were the incidence of dose-limiting toxicities (DLTs) and the incidence of treatment-related adverse events, and changes in clinical laboratory abnormalities. Please refer to NCT04896697 on www.clinicaltrials.gov for additional details. About Xilio Therapeutics Xilio Therapeutics is a clinical-stage biotechnology company discovering and developing tumor-activated immuno-oncology (I-O) therapies with the goal of significantly improving outcomes for people living with cancer without the systemic side effects of current I-O treatments. The company is using its proprietary geographically precise solutions (GPS) platform to build a pipeline of novel, tumor-activated molecules, including cytokines and other biologics, which are designed to optimize their therapeutic index and localize anti-tumor activity within the tumor microenvironment. Xilio is currently advancing multiple programs for tumor-activated I-O treatments in clinical development, as well as programs in preclinical development. Learn more by visiting www.xiliotx.com and follow us on Twitter (@xiliotx) and LinkedIn (Xilio Therapeutics, Inc.).

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