IL-15

Findings highlight tolerability and pharmacology of MTX-101 in humanized IL–15 transgenic mouse model SEATTLE, March 14, 2024 /PRNewswire/ -- Mozart Therapeutics, the leading developer of CD8 Treg modulators for the treatment of autoimmune and inflammatory diseases, today announce new non-clinical data for MTX-101. The data will be presented in a late-breaking poster presentation during the Society of Toxicology 63rd Annual Meeting, March 10‒14 in Salt Lake City, Utah. MTX-101 is an antibody-based bispecific autoimmune checkpoint inhibitor that selectively targets regulatory CD8 T cells. MTX-101 has limited cross-reactivity to its targets in animal models; therefore, a humanized IL-15 transgenic mouse model was utilized for non-clinical assessment of toxicity and pharmacology. Presentation highlights include: MTX-101 was well-tolerated following single and multiple doses in the humanized mouse model MTX-101 showed sustained binding to CD8 Treg and did not demonstrate off-target cell effects or cause an increase in detectable pro-inflammatory serum cytokines Serum concentrations of MTX-101 indicated high exposure and PK parameters consistent with antibodies Data derived from the humanized mouse model aligns with previous in vitro and in vivo findings for MTX-101 "We are pleased to present early data highlighting the non-clinical safety of MTX-101. Our data underline the utility of the humanized IL-15 transgenic mouse model to assess targeting human immune system receptors with limited cross-reactivity in conventional toxicology species," said Kristine Swiderek, Ph.D., Chief Scientific Officer at Mozart Therapeutics. "This model enables the non-clinical safety assessment and an understanding of the PK/PD relationship for MTX-101 to inform our clinical development strategy." The poster "Nonclinical Assessment of Toxicity and Pharmacology of MTX-101, a Novel KIRxCD8 Targeting Bispecific CD8 Treg Modulator, in Humanized Mouse" (Abstract #5081, Late-Breaking Session 3, March 14) can be accessed from the Mozart Therapeutics website. About MTX-101 MTX-101 is a bispecific CD8 Treg modulator targeting inhibitory KIR and CD8 expressed on regulatory CD8 T cells. This autoimmune checkpoint inhibitor aims to restore the intrinsic functions of regulatory CD8 T cells, acting early in the autoimmune disease process to suppress and eliminate pathogenic autoimmune cells, halt downstream inflammation, and prevent tissue destruction. About Mozart Therapeutics Mozart Therapeutics is focused on developing first-in-class disease-modifying therapies for autoimmune and inflammatory diseases, utilizing a novel approach to restoring immune system function by targeting the CD8 T regulatory network. The company is headquartered in Seattle, WA. For more information, visit and follow the company on LinkedIn @Mozart-tx. SOURCE Mozart Therapeutics

- Presented initial data from Phase 1 ELiPSE-1 Trial of CNTY-101 in relapsed/refractory B-cell lymphomas demonstrating a favorable tolerability profile, early clinical activity and indication that Allo-Evasion™ may support a multi-dosing regimen without the need for continued lymphodepletion - - Received investigational new drug (IND) clearance for CNTY-101 for the treatment ofsystemic lupus erythematosus (SLE); On track to initiate Phase 1 CALiPSO-1 clinical trial in the first half of 2024 - - Six posters to be presented at upcoming AACR Annual Meeting 2024 highlighting Century’s end-to-end cell therapy capabilities including expertise across iPSC reprogramming, gene editing, protein engineering, Allo-Evasion™ technology and computational biology - - Ended 2023 with cash, cash equivalents, and investments of $261.8 million; Cash runway into 2026 - PHILADELPHIA, March 14, 2024 (GLOBE NEWSWIRE) -- Century Therapeutics, Inc. (NASDAQ: IPSC), an innovative biotechnology company developing induced pluripotent stem cell (iPSC)-derived cell therapies in immuno-oncology and autoimmune and inflammatory disease, today reported financial results and business highlights for the full year ended December 31, 2023. "We enter 2024 following a series of significant milestones, highlighted by our presentation at ASH showcasing promising initial data from our ELiPSE-1 trial of CNTY-101. These findings not only revealed encouraging tolerability and early response signals in treating r/r B-cell lymphomas, but also unveiled the potential for a multi-dosing strategy while avoiding the need for continued lymphodepletion,” said Brent Pfeiffenberger, Pharm.D., Chief Executive Officer of Century Therapeutics. “The early success of our Allo-Evasion™ technology, demonstrated by the recent ELiPSE-1 data, bolsters our confidence in the potential of this approach for prolonged and tighter control over drug exposure as we anticipate expansion into autoimmune indications, marked by the recent IND clearance of CNTY-101 in SLE. We believe Century remains at the forefront of pioneering allogeneic cell therapy technology, exemplified by the early clinical activity of CNTY-101 in the ELiPSE-1 trial, the first clinical cell therapy candidate to be engineered with six precision gene edits for enhanced selectivity and persistence, and continued progress across our discovery and pipeline programs leveraging our integrated capabilities.” Research and Development Highlights and Upcoming Milestones CNTY-101 is an investigational off-the-shelf immunotherapy product candidate that utilizes iPSC-derived natural killer (NK) cells with a CD19-directed chimeric antigen receptor (CAR) and includes Century’s core Allo-Evasion™ edits designed to overcome the three major pathways of host versus graft rejection: CD8+ T cells, CD4+ T cells and NK cells. In addition, the product candidate is engineered to express IL-15 to provide homeostatic cytokine support, which has been in Century’s preclinical studies to improve functionality and persistence. Further, to potentially improve safety, the iNK cells were engineered with an EGFR safety switch, and proof-of-concept studies have demonstrated that the cells can be quickly eliminated by the administration of cetuximab, an antibody against EGFR approved by the U.S. Food and Drug Administration (FDA) for certain cancers. In December 2023, Century presented initial clinical data from the Phase 1 ELiPSE-1 Trial of CNTY-101 in relapsed/refractory (r/r) B-cell lymphomas. Findings supporting the potential for a multi-dosing strategy for CAR iNK enabled by Allo-Evasion™ edits were shared at the 65th American Society of Hematology (ASH) Annual Meeting. Data showed that CNTY-101 was well-tolerated at Dose Level 1 (100 million cells) in high-risk, heavily pretreated R/R B-cell lymphoma patients. The Company also shared a case study of one patient demonstrating a six-month durable complete response (CR) following multiple cycles of CNTY-101 without lymphodepletion. In December 2023, Century also shared results from additional patients in the ELiPSE-1 clinical trial of CNTY-101 treated at Dose Level 1, as well as preliminary data from patients treated at Dose Level 2 (300 million cells) demonstrating encouraging early response signals, including 2 CRs and 1 partial response (PR) out of 7 heavily pre-treated patients at these dose levels. CNTY-101 also demonstrated a favorable tolerability pro no initial evidence of allo-rejection. The Company believes these results support advancement to higher doses and a more dose intense regimen. The ability to prolong drug exposure by repeat dosing may provide significant treatment advantages in lymphoma, including enhanced objective response rates and duration of response. In December 2023, the Company received FDA clearance for the Investigational New Drug (IND) application of CNTY-101 in patients with moderate to SLE who have failed at least two standard immunosuppressive therapies. This represents the second IND clearance for CNTY-101 and the first in an autoimmune and inflammatory disease indication. Century plans to initiate a Phase 1 clinical trial, CALiPSO-1, in the first half of 2024, with initial data expected by year-end 2024. Century plans to share six poster presentations at the 2024 American Association for Cancer Research (AACR) Annual Meeting being held on April 5-10, 2024, in San Diego, California, showcasing Century’s recent research in enhancing the safety and efficacy of its iPSC-derived treatment candidates for oncology and immunology indications. The upcoming abstracts highlight the Company’s end-to-end capabilities in iPSC reprogramming and differentiation, gene editing, protein engineering and computational biology. Additionally, the Company will share new preclinical data on additional Allo-Evasion™ edits that could further support Century’s multi-dosing strategy. The following abstracts are currently available through the AACR conference website, and the posters will be made available on the Century website following the presentations: Engineered Expression Of HLA-E And HLA-G Protects iPSC-Derived Cells from Killing by Primary NK Cells CXCR4 Transgene Improves In Vivo Migration and Efficacy of Engineered iPSC-Derived Natural Killer Cells Screening iPSC Lines for Optimal Characteristics of Differentiation into Immune Effector Cells for Clinical Programs Discovery of a Novel Nectin-4 iPSC-derived Cell Therapy for the Treatment of Solid Tumors The Discovery of a Novel CD19xCD22 Dual-Targeting CAR For the Development of an iPSC-Derived Cell Therapy Discovery Of Inhibitory CAR Target DSG1 For Damping Nectin-4 On-Target Off-Tumor Toxicity in iPSC-Derived CAR-T Cell Therapy Business Highlights In November 2023, the Company announced the appointment of Brent Pfeiffenberger, Pharm.D., MBA, as Chief Executive Officer. In November 2023, Century and FUJI Cellular Dynamics (FCDI) announced a worldwide license agreement where FCDI granted Century non-exclusive licenses for the development and commercialization of cell therapies derived from iPSCs for the treatment of autoimmune and inflammatory diseases. Additionally, they announced the expansion of their existing 2018 license agreements for iPSC-derived cancer immunotherapeutics. Full Year 2023 Financial Results Cash Position: Cash, cash equivalents, and marketable securities were $261.8 million as of December 31, 2023, as compared to $367.4 million as of December 31, 2022. Net cash used in operations was $88.3 million for the twelve months ended December 31, 2023, compared to net cash provided by operations of $14.1 million for the twelve months ended December 31, 2022 (which includes deferred revenue from the Bristol Myers Squibb (BMS) collaboration of $118.0 million). Collaboration Revenue: Collaboration revenue generated through the Company’s collaboration, option, and license agreement with Bristol-Myers Squibb (BMS) was $2.2 million for the year ended December 31, 2023, compared to $5.2 million for the same period in 2022. Research and Development (R&D) expenses: R&D expenses were $92.7 million for the year ended December 31, 2023, compared to $97.2 million for the year ended December 31, 2022. The decrease in R&D expenses was primarily due to the Company’s 2023 reorganization and reprioritization of early-stage programs and discovery platforms as well as a decline in sponsored research activities. General and Administrative (G&A) expenses: G&A expenses were $34.7 million for the year ended December 31, 2023, compared to $31.9 million for the year ended December 31, 2022. The increase in G&A expenses was primarily due to increases in stock-based compensation and recruiting fees. Impairment of Long-lived Assets: A one-time impairment charge of $16.4 million was recorded in connection with the strategic decision to consolidate three of the Company’s existing leased facilities in Philadelphia as well as one in Seattle. In-Process Research and Development: In-process research and development expenses were $5.0 million for the year ended December 31, 2023, compared to $10.0 million for the year ended December 31, 2022. In 2023, $4.0 million was a result of entering into a worldwide license agreement with FCDI for the development and commercialization of iPSC-derived therapies for treatment of inflammatory and autoimmune diseases, and $1.0 million related to a milestone fee paid pursuant to the license for filing of the IND for CNTY-101 in SLE. Net Loss: Net loss was $136.7 million for the year ended December 31, 2023, compared to $131.0 million for the year ended December 31, 2022. Financial Guidance The Company expects full year generally accepted accounting principles (GAAP) operating expenses to be between $135 million and $145 million. The Company estimates its cash, cash equivalents, and investments will support operations into 2026. About Century Therapeutics Century Therapeutics (NASDAQ: IPSC) is harnessing the power of adult stem cells to develop curative cell therapy products for cancer and autoimmune and inflammatory diseases that we believe will allow us to overcome the limitations of first-generation cell therapies. Our genetically engineered, iPSC-derived cell product candidates are designed to specifically target hematologic and solid tumor cancers, with a broadening application to autoimmune and inflammatory diseases. We are leveraging our expertise in cellular reprogramming, genetic engineering, and manufacturing to develop therapies with the potential to overcome many of the challenges inherent to cell therapy and provide a significant advantage over existing cell therapy technologies. We believe our commitment to developing off-the-shelf cell therapies will expand patient access and provide an unparalleled opportunity to advance the course of cancer and autoimmune and inflammatory disease care. For more information on Century Therapeutics please visit . Forward-Looking Statements This press release contains forward-looking statements within the meaning of, and made pursuant to the safe harbor provisions of, The Private Securities Litigation Reform Act of 1995. All statements contained in this press release, other than statements of historical facts or statements that relate to present facts or current conditions, including but not limited to, statements regarding our clinical development plans and timelines and financial guidance, are forward-looking statements. These statements involve known and unknown risks, uncertainties and other important factors that may cause our actual results, performance, or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements. In some cases, you can identify forward-looking statements by terms such as “may,” “might,” “will,” “should,” “expect,” “plan,” “aim,” “seek,” “anticipate,” “could,” “intend,” “target,” “project,” “contemplate,” “believe,” “estimate,” “predict,” “forecast,” “potential” or “continue” or the negative of these terms or other similar expressions. The forward-looking statements in this press release are only predictions. We have based these forward-looking statements largely on our current expectations and projections about future events and financial trends that we believe may affect our business, financial condition, and results of operations. These forward-looking statements speak only as of the date of this press release and are subject to a number of risks, uncertainties and assumptions, some of which cannot be predicted or quantified and some of which are beyond our control, including, among others: our ability to successfully advance our current and future product candidates through development activities, preclinical studies, and clinical trials; our dependence on the success of our lead product candidate, CNTY-101; the ability of CNTY-101 to be administered as part of a multi-dose strategy and to enable responses without lymphodepletion; uncertainties inherent in the results of preliminary data, pre-clinical studies and earlier-stage clinical trials, which may not be predictive of final results or the results of later-stage clinical trials; the timing of and our ability to initiate and successfully enroll the Phase 1 SLE trial; our ability to obtain FDA clearance of our future IND submissions and commence and complete clinical trials on expected timelines, or at all; our reliance on the maintenance of certain key collaborative relationships for the manufacturing and development of our product candidates; the timing, scope and likelihood of regulatory filings and approvals, including final regulatory approval of our product candidates; the impact of geopolitical issues, banking instability and inflation on our business and operations, supply chain and labor force; the performance of third parties in connection with the development of our product candidates, including third parties conducting our clinical trials as well as third-party suppliers and manufacturers; our ability to successfully commercialize our product candidates and develop sales and marketing capabilities, if our product candidates are approved; our ability to recruit and maintain key members of management and our ability to maintain and successfully enforce adequate intellectual property protection. These and other risks and uncertainties are described more fully in the “Risk Factors” section of our most recent filings with the Securities and Exchange Commission and available at You should not rely on these forward-looking statements as predictions of future events. The events and circumstances reflected in our forward-looking statements may not be achieved or occur, and actual results could differ materially from those projected in the forward-looking statements. Moreover, we operate in a dynamic industry and economy. New risk factors and uncertainties may emerge from time to time, and it is not possible for management to predict all risk factors and uncertainties that we may face. Except as required by applicable law, we do not plan to publicly update or revise any forward-looking statements contained herein, whether as a result of any new information, future events, changed circumstances or otherwise. For More Information: Investors and media: Julie Seidel/ Noor Pahlavi – century@argotpartners.com Century Therapeutics, Inc Condensed Balance Sheets (unaudited, in thousands) December 31, December 31, Assets 2023 2022 Current Assets: $ $ Cash and cash equivalents 47,324 84,265 Short-term investments 125,414 231,233 Prepaid expenses and other current assets 4,256 4,223 Total current assets 176,994 319,721 Property and equipment, net 71,705 82,785 Operating lease right-of-use assets, net 20,376 28,945 Long-term investments 89,096 51,854 Other long-term assets 2,520 3,239 Total assets $ 360,691 $ 486,544 Liabilities, convertible preferred stock, and stockholders' equity Current liabilities: Accounts payable $ 2,741 $ 5,454 Accrued expenses and other liabilities 10,733 10,707 Long-term debt, current - 6,502 Deferred revenue, current 4,372 7,154 Total current liabilities 17,846 29,817 Operating lease liability, noncurrent 46,658 38,698 Long-term debt, net - 3,739 Other long-term liabilities 56 718 Deferred revenue 111,381 110,834 Total liabilities 175,941 183,806 Stockholders' equity Common stock 6 6 Additional paid-in capital 840,407 824,292 Accumulated deficit (655,771 ) (519,098 ) Accumulated other comprehensive loss 108 (2,462 ) Total stockholders' equity 184,750 302,738 Total liabilities and stockholders' equity $ 360,691 $ 486,544 Nine months Ended December 31, December 31, 2023 2022 Collaboration Revenue $ 2,235 $ 5,199 Operating Expenses Research and development $ 92,710 $ 97,173 General and administrative 34,706 31,857 In-process research and development 5,000 10,000 Impairment on long-lived assets 16,365 - Total operating expenses $ 148,781 $ 139,030 Loss from operations (146,546 ) (133,831 ) Interest expense (540 ) (1,430 ) Interest income 12,677 4,420 Other income, net (383 ) - Loss before provision for income taxes $ (134,792 ) $ (130,841 ) Provision for income taxes (1,881 ) (91 ) Net Loss $ (136,673 ) $ (130,932 ) Unrealized gain (loss) on investments 2,602 (1,786 ) Foreign currency translation adjustment (loss) (32 ) (26 ) Comprehensive loss (134,103 ) (132,744 ) Net loss per common share - Basic and Diluted (2.30 ) (2.27 ) Weighted average common shares outstanding 59,314,389 57,755,842

Replay’s cell therapy product company Syena announces first patient dosed in Phase 1/2 study of TCR-NK cell therapy for multiple myeloma Phase 1/2 clinical study of NY-ESO-1 TCR/IL-15 NK for relapsed or refractory multiple myeloma commences on track NY-ESO-1 TCR/IL-15 NK is the lead clinical program of Syena, a Replay and MD Anderson cell therapy company based on the scientific discoveries of Professor Katy Rezvani, M.D., Ph.D. Syena is Replay’s first product company to enter clinical development San Diego, California, London, UK, and Houston, Texas, March 11, 2024 – Replay, a genome writing company reprogramming biology by writing, designing, and delivering big DNA, today announced that the first patient has been dosed in the Phase 1/2 study of NY-ESO-1 TCR/IL-15 NK, an engineered T-Cell Receptor Natural Killer (TCR-NK) cell therapy for relapsed or refractory multiple myeloma. NY-ESO-1 TCR/IL-15 NK is being developed by Syena, an oncology-focused product company launched by Replay and The University of Texas MD Anderson Cancer Center,, based on the scientific discoveries of Katy Rezvani, MD, PhD, Professor of Stem Cell Transplantation & Cellular Therapy at MD Anderson. Syena has an exclusive licensing agreement for MD Anderson’s TCR-NK technology platform. This first-in-class engineered cell therapy comprises cord blood-derived natural killer cells that express an affinity-enhanced TCR targeted against the NY-ESO-1 antigen. NY-ESO-1 is highly immunogenic and expressed on numerous cancer cell types. The ability of NY-ESO-1 to elicit humoral and cellular immune responses along with its restricted tissue expression makes it a compelling target for cancer immunotherapy. The Phase 1/2 clinical study will assess the safety and efficacy of NY-ESO-1 TCR/IL-15 NK in patients with relapsed or refractory multiple myeloma. It will be administered following lymphodepletion with standard doses of fludarabine/cyclophosphamide (Flu/Cy). The study will enrol up to 44 patients in total. Adrian Woolfson, Executive Chairman, President, and Co-Founder of Replay, said: “The dosing of the first patient in Syena’s NY-ESO-1 TCR-NK clinical study represents a major step forward in addressing the significant unmet medical need for ‘off-the-shelf’ cell therapies. I am delighted with the rapid progress that we have made to date. NY-ESO-1 is highly expressed in poor-prognosis multiple myeloma, making this a suitable indication for demonstrating proof of concept for Syena’s TCR-NK technology platform. We believe that the use of optimally selected cord blood donors is likely to translate into improved patient outcomes. We are grateful to the patients, clinical sites, and development teams for their ongoing commitment and efforts to advance this new technology into the clinic.” Lachlan MacKinnon, CEO and Co-Founder of Replay, commented: “This Phase 1/2 clincial study will be key to further understanding the potential of our TCR-NK platform, with Syena making significant strides towards delivering its pioneering first-in-class TCR-NK cell therapy to patients with relapsed or refractory multiple myeloma. We look forward to enrolling further patients and evaluating the safety and efficacy outcomes as the study progresses.” For more information please visit ClinicalTrials.gov and reference identifier NCT06066359. Ends About Replay Replay is a genome writing company, which aims to define the future of genomic medicine through reprogramming biology by writing, designing, and delivering big DNA. The Company has assembled a toolkit of disruptive platform technologies — including a high payload capacity HSV delivery platform — to address the challenges currently limiting clinical progress and preventing genomic medicine from realizing its potential. The Company’s hub-and-spoke business model separates technology development within Replay from therapeutic development in a portfolio of product companies that leverage its technology platforms. The Company recently incorporated a first-in-class engineered TCR-NK cell therapy product company, Syena, using technology developed by Katy Rezvani, MD, PhD, at The University of Texas MD Anderson Cancer Center in Houston, Texas. Replay’s synHSV™ technology, a high payload capacity HSV vector capable of delivering up to 30 times the payload of AAV, is used by Replay’s gene therapy product companies, bringing big DNA treatments to monogenic diseases impacting the skin, and eye. Replay is led by a distinguished team of academics, entrepreneurs, and industry experts. The Company has raised $85 million to date and is supported by an international syndicate of investors including: KKR, OMX Ventures, ARTIS Ventures, Lansdowne Partners and the Bill and Melinda Gates Foundation. Replay is headquartered in San Diego, California. For further information please visit and follow us on LinkedIn and Twitter. About NY-ESO-1 TCR/IL-15 NK NY-ESO-1 TCR/IL-15 NKs are adoptive Natural Killer (NK) cells expressing an affinity-enhanced T-cell receptor (TCR) directed against NY-ESO-1-specific cord blood-derived NK cells. The cells are engineered to express the CD3 and TCR signalling complex and IL-15, and use the same manufacturing method as engineered CAR-NKs, which have demonstrated safety and efficacy in lymphoma (Liu et al, NEJM 2020 and Marin et al Nature Medicine 2024). NY-ESO-1 (New York Esophageal Squamous cell carcinoma 1) is an cancer-testis antigen with re-expression in multiple cancer types, and restricted expression in healthy tissues. This expression pattern and its ability to elicit humoral and cellular immune responses makes it a compelling target for TCR-T cell therapy. TCR-engineered NK cells retain their capacity to target tumor cells through their native receptors. The ability of NK cells to target tumor cells that down-regulate or lack MHC through the ‘missing self’ mechanism, may make disease escape through the most common mechanism of acquired resistance, less likely. IND-enabling studies have confirmed that NY-ESO-1 TCR/IL-15 NK cells do not kill healthy human cell lines derived from organs including the heart, lungs, liver, and kidneys. Contacts: Replay Dr. Adrian Woolfson/Lachlan MacKinnon info@replay.bio ICR Consilium – media relations Amber Fennell/Tracy Cheung/David Daley replay@consilium-comms.com