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CAMBRIDGE, Mass., Dec. 12, 2022 (GLOBE NEWSWIRE) -- Magenta Therapeutics (Nasdaq: MGTA), a clinical-stage biotechnology company developing novel medicines designed to bring the curative power of stem cell transplant to more patients, highlights updated clinical data from the ongoing MGTA-117 Phase 1/2 dose-escalation clinical trial made in an oral presentation today at the American Society of Hematology 2022 Annual (ASH) Meeting in New Orleans and provides program updates across the portfolio. “We have shown that a single dose of MGTA-117 binds target cells, depletes target cells, clears the body quickly as designed, and does so with a favorable tolerability profile in our ongoing Phase 1/2 clinical trial. We believe that these positive clinical data establishes proof-of-mechanism, and that we have reached an active dose. Target cell depletion is a critical measurement of success for MGTA-117, and we are encouraged by the levels of depletion we have observed in both the blood and the bone marrow of relapsed/refractory acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) patients. We are excited about our planned next steps to take MGTA-117 into transplant-eligible AML and MDS patients as well as into patients who are receiving gene therapy. We are thankful to all of the patients and families who have participated in our trial to date as well as our investigators and the clinical site staff, all of whom have contributed greatly to the advancement of MGTA-117 for patients,” said Jason Gardner, President and Chief Executive Officer of Magenta Therapeutics. “Together with the progress we are making on CD45-ADC and MGTA-145, we are pleased with the momentum across our portfolio and the multiple anticipated inflection points for Magenta in the coming year.” MGTA-117 Clinical Data and Continued Development MGTA-117 is Magenta’s most advanced targeted conditioning product candidate designed to deplete CD117-expressing target cells in the blood and/or bone marrow prior to a patient undergoing stem cell transplant or receiving an ex vivo gene therapy product. MGTA-117 is an anti-CD117 antibody conjugated to an amanitin payload. CD117, also known as c-Kit receptor, is highly expressed on hematopoietic stem cells, progenitor cells and cancer blast cells. Current Phase 1/2 Patient Population and Potential Significance for Clinical Development The ongoing Phase 1/2 clinical trial is in relapsed/refractory (R/R) AML and MDS. These patients are deemed ineligible for transplant due to active disease characterized by high numbers of cancer blast cells present in the bone marrow and in the bloodstream. Over 80% of patients with AML and MDS express the CD117 receptor on the surface of their cancer cells. In these patients, CD117+ target cells are a combination of cancer blast cells in the blood and bone marrow and non-malignant stem and progenitor cells in the bone marrow. MGTA-117 is designed to target all of these cells, and clinical evidence of depletion in this patient population provides valuable support that MGTA-117 will robustly deplete target cells in the proposed next phase of development in (i) transplant-eligible AML and MDS patients who have significantly lower numbers of cancer blast cells and (ii) gene therapy patients who have no cancer blast cells. Therefore, Magenta expects MGTA-117 to bind and deplete target cells in the bone marrow in these patient populations, and potentially achieve greater levels of depletion, at the same dose levels studied in R/R AML and MDS patients. MGTA-117 Proof-of-Mechanism and Potential Active Dose Participants Dosed & Available Data. As of December 1, 2022, a total of 15 participants have been dosed with MGTA-117 in Cohorts 1, 2 and 3. All dosed participants contributed data in whole or in part to the preliminary data set depending on an individual’s availability for collecting assessments. Eleven of the 15 dosed participants completed the dose-limiting toxicity safety observation period of 21 days. None of the four participant discontinuations were deemed to be related to MGTA-117. Target Cell Binding. MGTA-117 bound to CD117-expressing target cells within 15 minutes after dosing in all participants as measured by a receptor occupancy (RO) assay. RO increased with higher dose levels of MGTA-117. The percentage of occupied CD117 receptors was greater, and the receptor occupancy was more durable at the higher dose levels of Cohorts 2 and 3 as compared to Cohort 1 as expected. Target Cell Depletion. Depletion in Blood and Bone Marrow. MGTA-117 showed greater depletion of target cancer blast cells in the blood of participants in Cohorts 2 and 3 compared to Cohort 1. In addition, three out of the four participants in Cohort 3 for whom paired bone marrow samples were collected at baseline and post-dosing had depletion of cancer blast cells in both blood and bone marrow. This matched depletion response in the blood and bone marrow provides evidence of an active dose and dose-dependent depletion of CD117-expressing cells. Two Transplant-Ineligible Participants Became Transplant-Eligible. Participants entering the clinical trial were considered ineligible for stem cell transplant and had active and persistent AML/MDS after receiving one or more anti-leukemic therapies. One relapsed/refractory MDS participant in Cohort 3 had a reduction of bone marrow cancer blast cells to a level that enabled the participant to become eligible for transplant. This is the trial’s second participant who became eligible for transplant after a single dose of MGTA-117. The first participant, from Cohort 1, had relapsed/refractory AML and was previously disclosed. Clearance. MGTA-117 was shown to be rapidly cleared from the body as expected. No MGTA-117 was detectable in the blood 48 hours after dosing in Cohorts 1 and 2, and over 95% of MGTA-117 was cleared in the blood 48 hours after dosing at the higher dose level of Cohort 3. Rapid clearance of MGTA-117 was engineered into the molecule to ensure avoidance of depleting newly transplanted donor cells in allogeneic transplant or, in the case of gene therapy, of autologous gene-modified cells. In addition, the MGTA-117 ADC was shown to be stable in blood over time in all participants, and no free payload was detectable in the blood of any participants at any time point. Tolerability. MGTA-117 was well-tolerated in all participants. No serious adverse events were deemed to be related to MGTA-117, and no dose-limiting toxicities were observed. Treatment-related adverse events deemed to be related to MGTA-117 were low-grade liver enzyme elevations, low-grade fever, and grade 3 and grade 4 leukopenia in two participants who had baseline grade 2 and grade 3 leukopenia, respectively. All instances of observed liver enzyme elevations were low-grade, transient and resolved without intervention, as expected. Continued Trial Progress and Data Expectations. The Phase 1/2 clinical trial is currently enrolling in Cohort 4 (0.13 mg/kg) and Magenta anticipates presenting aggregate clinical data from the clinical trial, including Cohort 4, at a scientific conference in Q1 2023. MGTA-117 Regulatory Engagement and Clinical Development Next Steps in Transplant-Eligible AML/MDS and Autologous Gene Therapy As previously disclosed, Magenta has initiated formal engagements with regulatory agencies to transition MGTA-117 into a transplant-eligible AML and MDS patient population. Magenta also plans to engage regulators in H1 2023 for the purposes of initiating a MGTA-117 clinical trial in autologous ex vivo gene therapy. Transplant-Eligible AML and MDS. Magenta anticipates that MGTA-117’s pharmacokinetics (PK), pharmacodynamics (PD) and tolerability in Cohorts 1-3 will support alignment with regulatory authorities to study MGTA-117 in AML and MDS transplant-eligible patients. Importantly, the proposed study design in the transplant setting will allow for the measurement of depletion of CD117-expressing cells in the bone marrow after a single dose of MGTA-117 prior to reduced-intensity conditioning (RIC) and the ensuing allogeneic transplant. By depleting residual cancer blast cells prior to a standard RIC regimen, MGTA-117 has the potential to boost disease control prior to transplant and improve disease outcomes post-transplant. These potential positive outcomes could address the current significant unmet need associated with RIC-conditioning where AML and MDS patients relapse at a rate of 40%-50% within six months post-transplant1. Pending regulatory alignment, Magenta plans to share additional details of the proposed transplant-eligible MGTA-117 study design in Q1 2023. Gene Therapy. Magenta expects to use the clinical data package from the ongoing Phase 1/2 trial, together with supporting insights from PK/PD modeling, to engage with regulators on a potential MGTA-117 clinical trial in autologous ex vivo gene therapy. In a gene therapy clinical trial, Magenta anticipates dosing patients with MGTA-117 to deplete stem and progenitor cells before the patient receives an infusion of gene-modified stem cells, with a goal of replacing the current standard-of-care conditioning that relies on high doses of chemotherapeutic agents such as busulfan, which is known to be carcinogenic. Magenta anticipates sharing more details in 2023 as development plans progress in collaboration with gene therapy partners. Magenta has existing clinical collaborations with gene therapy companies and anticipates entering into additional collaborations as MGTA-117 development advances. CD45-ADC IND-Enabling Plans Magenta’s CD45-ADC is a second targeted conditioning ADC, designed to selectively target and deplete both stem cells and immune cells, and is intended to replace the use of chemotherapy-based conditioning prior to stem cell transplant in patients with blood cancers and autoimmune diseases. As previously disclosed, Good Manufacturing Practice (GMP) manufacturing and other investigative new drug application (IND)-enabling activities are ongoing for the CD45-ADC program. A Good Laboratory Practice (GLP) toxicology study is expected to be completed in H2 2023. Magenta anticipates regulatory interactions prior to filing an IND and anticipates providing further details on the CD45-ADC program in 2023, including molecule design, key preclinical data, and timelines to IND. MGTA-145 Phase 2 Progress Magenta is developing MGTA-145, in combination with plerixafor, to improve the process by which stem cells are released out of the bone marrow and into the bloodstream, known as stem cell mobilization. The mobilized cells are then collected and available for transplant. This is the first step for patients and is required for the majority of transplants and stem cell gene therapies. Magenta, in partnership with bluebird bio, is enrolling patients in a Phase 2 clinical trial evaluating the ability of MGTA-145 in combination with plerixafor to mobilize stem cells for collection in patients with sickle cell disease. Due to enrollment delays at the clinical sites that are unrelated to MGTA-145, Magenta anticipates disclosing clinical data in H1 2023. Conference Call Information: Magenta will host a conference call and webcast at 8:30 a.m. Eastern Time / 7:30 a.m. Central Time tomorrow, Tuesday, December 13, 2022 to review the MGTA-117 data presented at the 2022 ASH Annual Meeting. To access the conference call, please register online at https://register.vevent.com/register/BI872661cff05d4191a7bb100830aae147. Upon registering, each participant will be provided with call details and a conference ID. The live webcast of the call and slide deck may be accessed at https://edge.media-server.com/mmc/p/hk2eojv2, or by visiting the Investors & Media section of the company's website at https://investor.magentatx.com. A replay of the webcast will be available shortly after the conclusion of the call and will be archived on the Events & Presentations page. 1 Scott, Journal of Clinical Oncology 2017. https://pubmed-ncbi-nlm-nih-gov.libproxy1.nus.edu.sg/28380315/ About Magenta Therapeutics Magenta Therapeutics is a clinical-stage biotechnology company developing medicines designed to bring the curative power of stem cell transplant to more patients with blood cancers, genetic diseases and autoimmune diseases. Magenta is combining leadership in stem cell biology and biotherapeutics development with clinical and regulatory expertise to revolutionize blood and immune reset to allow more patients to take advantage of the curative potential of stem cell transplant and potentially improve eligibility for future gene therapies. Magenta is based in Cambridge, Mass. For more information, please visit www.magentatx.com. Follow Magenta on Twitter: @magentatx

New clinical results from ongoing MGTA-117 Phase 1/2 clinical trial support earlier observations of target binding, target cell depletion, rapid drug clearance and a favorable tolerability profile; clinical trial has progressed into the third dose escalation cohort; oral presentation of clinical data will be given at the 2022 American Society of Hematology (ASH) meeting in December 2022 CD45 antibody-drug conjugate (ADC) dose-ranging toxicology study successfully completed; IND-enabling studies advancing; program update and development timeline guidance anticipated in December 2022 MGTA-145 stem cell mobilization clinical trial in sickle cell disease patients is enrolling with early clinical data expected in December 2022 Approximately $128.3 million in cash, cash equivalents and marketable securities at the end of Q3 2022; maintains guidance that cash reserves are expected to fund current operating plan into Q2 2024 CAMBRIDGE, Mass., Nov. 03, 2022 (GLOBE NEWSWIRE) -- Magenta Therapeutics (Nasdaq: MGTA), a clinical-stage biotechnology company developing novel medicines designed to bring the curative power of stem cell transplant to more patients, today reported financial results for the third quarter ending September 30, 2022, and recent program highlights. “We are building momentum in the MGTA-117 clinical trial with new clinical results and are making progress across our pipeline, including our second targeted conditioning program CD45-ADC,” said Jason Gardner, President and Chief Executive Officer of Magenta Therapeutics, Inc. “In the MGTA-117 Phase 1/2 clinical trial, we continue to enroll and generate clinical data in higher-dose cohorts. Our preclinical work has been particularly helpful in predicting our clinical experience in these early dose cohorts regarding MGTA-117 activity at different exposure levels and the overall tolerability profile. We look forward to presenting available clinical data at ASH and using our data to support interactions with regulators as we plan to advance MGTA-117 to stem cell transplant-eligible patients and into gene therapy.” Program Highlights: MGTA-117 Phase 1/2 Clinical Trial Progression and Data Disclosure Expectations MGTA-117 is Magenta’s most advanced targeted conditioning product candidate designed to deplete target cells prior to a patient undergoing stem cell transplant or receiving an ex vivo gene therapy product. The program is currently enrolling patients with relapsed/refractory acute myeloid leukemia (AML), and myelodysplastic syndromes (MDS), in a Phase 1/2 dose escalation clinical trial. MGTA-117 is an anti-CD117 antibody conjugated to an amanitin payload. CD117, also known as c-Kit receptor, is highly expressed on hematopoietic stem cells, progenitor cells, and leukemic cells. Enrollment Progress. Magenta has completed enrollment in Cohort 1 and Cohort 2. In addition, Magenta has enrolled a sufficient number of patients to complete Cohort 3, provided that the patients complete their respective dose-limiting toxicity (DLT) observation periods. No serious adverse events have been deemed to be related to MGTA-117, and no dose-limiting toxicities have been observed to date. Our clinical experience has confirmed that patients with relapsed/refractory AML are at high risk for multiple disease complications, including susceptibility to infection, all of which can rapidly progress at any time leading to severe morbidity or mortality. All enrolled patients have contributed data to the clinical trial independent of the completion of the DLT period. Proof-of-Mechanism. Available clinical data, including new data since the ASH abstract submission in August 2022, support proof-of-mechanism for MGTA-117 due to evidence of its ability to bind CD117-expressing cells, deplete CD117-expressing cells, clear the body rapidly and be well-tolerated. Regulatory Plans. Magenta has initiated requests for formal engagement with multiple regulatory authorities for the purpose of transitioning the clinical program into transplant-eligible AML and MDS patients. The pending regulatory interactions are expected to focus on MGTA-117’s clinical data relating to target binding, drug clearance and stability and tolerability across multiple dose levels. All available clinical data will be used to support these regulatory interactions, as well as the predictive preclinical modeling in non-human primates that has closely matched our clinical experience to date. Gene Therapy. Magenta expects data from the Phase 1/2 trial to also inform clinical development planning and enable regulatory engagements for MGTA-117 as a potential monotherapy prior to patients undergoing autologous ex vivo gene therapy. Magenta has existing clinical collaborations with gene therapy companies and anticipates entering into additional collaborations as data progresses. ASH Presentations. As disclosed separately, Magenta will present clinical and preclinical data at the American Society of Hematology (ASH) Annual Meeting in December 2022. The MGTA-117 clinical presentation will include data on pharmacokinetics, pharmacodynamic activity and the tolerability of MGTA-117. In light of the need to collect and finalize complete Cohort 3 data, Magenta currently anticipates presenting Cohort 1 and Cohort 2 clinical data at ASH. Any data not included in the ASH presentation is anticipated to be available at a scientific conference in Q1 2023. CD45-Antibody Drug Conjugate (ADC): Second Targeted Conditioning Program Magenta’s CD45-ADC is designed to selectively target and deplete both stem cells and immune cells and is intended to replace the use of chemotherapy and radiation-based conditioning prior to stem cell transplant in patients with blood cancers and autoimmune diseases. Magenta has completed a dose-ranging toxicology preclinical study successfully with no unexpected findings. The data inform dosing for a Good Laboratory Practices toxicology study intended to support a planned Investigational New Drug (IND) application. Manufacturing and other IND-enabling activities are ongoing, and Magenta is preparing for regulatory interactions and clinical development activities. Magenta expects to provide a further update on the CD45-ADC program in December 2022. MGTA-145 Stem Cell Mobilization and Collection Magenta is developing MGTA-145, in combination with plerixafor, to improve the process by which stem cells are released out of the bone marrow and into the bloodstream, known as stem cell mobilization. The mobilized cells are then collected and available for transplant. This is the first step for patients and is required for the majority of transplants and stem cell gene therapies. Magenta, in partnership with bluebird bio, has initiated a Phase 2 clinical trial in sickle cell disease to evaluate the utility of MGTA-145, in combination with plerixafor, for the mobilization and collection of stem cells in patients with sickle cell disease. Mobilization and collection are difficult in sickle cell disease patients where granulocyte colony-stimulating factor (GCSF) cannot be used, and there is a clear unmet medical need. Magenta anticipates generating initial data from this clinical trial in December 2022 followed by a more comprehensive data set in H1 2023. Financial Results: Cash Position: Cash, cash equivalents and marketable securities as of September 30, 2022, were $128.3 million, compared to $176.9 million as of December 31, 2021. The September cash balance includes gross proceeds of $3.0 million from our “at-the-market” facility. Magenta anticipates that its cash, cash equivalents and marketable securities will be sufficient to fund its current operational plan into Q2 2024. Research and Development Expenses: Research and development expenses were $11.2 million in the third quarter of 2022, compared to $10.8 million in the third quarter of 2021. The increase was driven primarily by higher preclinical and manufacturing costs to support our IND-enabling studies for CD45-ADC, offset by a decrease in clinical trial costs related to our mobilization program. General and Administrative Expenses: General and administrative expenses were $6.1 million for the third quarter of 2022, compared with $7.5 million in the third quarter of 2021. The decrease was primarily due to a decrease in stock-based compensation. Net Loss: Net loss was $16.1 million for the third quarter of 2022, compared to net loss of $17.4 million for the third quarter of 2021. About Magenta Therapeutics Magenta Therapeutics is a clinical-stage biotechnology company developing medicines designed to bring the curative power of stem cell transplant to more patients with blood cancers, genetic diseases and autoimmune diseases. Magenta is combining leadership in stem cell biology and biotherapeutics development with clinical and regulatory expertise to revolutionize blood and immune reset to allow more patients to take advantage of the curative potential of stem cell transplant and potentially improve eligibility for future gene therapies. Magenta is based in Cambridge, Mass. For more information, please visit Follow Magenta on Twitter: @magentatx. Forward-Looking Statements This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995, as amended. These statements include, without limitation, implied and express statements relating to: Magenta’s future business expectations, plans and prospects; the potential of, and expectations for, Magenta’s product candidate pipeline; the potential benefits and expected performance of Magenta’s product candidates and programs; the development of product candidates and advancement of preclinical and clinical programs, including, without limitation, patient enrollment; expectations, plans and timing for preclinical activities, clinical trials and related results involving Magenta’s product candidates; expectations, plans and timing for the generation, receipt and disclosure of preclinical and clinical trial data, toxicology results, and other results involving Magenta’s product candidates; timing for the disclosure of developmental timelines, developmental plans and program updates regarding Magenta’s product candidates; timelines and expectations for dosing, dosing regimens and administration; the use of data to support interactions with regulators as Magenta plans to advance MGTA-117 to stem cell transplant-eligible patients and into gene therapy; the completion of dose-limiting toxicity observation periods; regulatory interactions; the planned transition of the MGTA-117 Phase 1/2 clinical trial into transplant-eligible AML and MDS patients; expectations that regulatory interactions will focus on MGTA-117’s clinical data relating to target binding, drug clearance and stability and tolerability across multiple dose levels; the planned use of available clinical data to support regulatory interactions, as well as the predictive preclinical modeling in non-human primates that has closely matched Magenta’s clinical experience; expectations that data from the Phase 1/2 trial will inform clinical development planning and enable regulatory engagements for MGTA-117 as a potential monotherapy prior to patients undergoing autologous ex vivo gene therapy; the predictive value of Magenta’s MGTA-117 preclinical modeling; whether present results will collectively inform the continued development of MGTA-117; the anticipation of entering into additional collaborations as data progresses; that data from a dose-ranging toxicology preclinical study for CD45-ADC inform dosing for a Good Laboratory Practices toxicology study intended to support a planned Investigational New Drug application; the expectation that clinical data from additional dose-escalation cohorts will support Magenta’s prior clinical observations and data in the MGTA-117 Phase 1/2 clinical trial in patients with relapsed/refractory AML and MDS; the anticipated benefits of Magenta’s revised operating plan; and Magenta’s current anticipation and guidance regarding the ability of its cash, cash equivalents and marketable securities to fund its current operating plan into Q2 2024. Words such as “anticipate,” “believe,” “continue,” “could,” “designed,” “endeavor,” “estimate,” “expect,” “intend,” “may,” “might,” “plan,” “potential,” “predict,” “project,” “seek,” “should,” “target,” “preliminary,” “will,” “would” and similar expressions are intended to identify forward-looking statements. The express or implied forward-looking statements included in this press release are only predictions and are subject to a number of risks, uncertainties and assumptions, including, without limitation: volatility and uncertainty in the capital markets for biotechnology companies; uncertainties inherent in preclinical and clinical trials and in the availability and timing of data from ongoing and planned clinical and preclinical trials; the ability to initiate, enroll, conduct or complete ongoing and planned preclinical and clinical trials; vulnerability and/or fragility of, and the presence of underlying disorders in, the patient population for the clinical trials of Magenta’s product candidates, including the MGTA-117 Phase 1/2 clinical trial in patients with relapsed/refractory AML and MDS; the delay of any current or planned preclinical or clinical trials, or the delay in development of Magenta’s product candidates; whether results from preclinical or earlier clinical trials will be predictive of the results of future trials; interactions with regulatory agencies such as the U.S. Food and Drug Administration; the expected timing of submissions for regulatory approval to conduct or continue trials or to market products; Magenta’s ability to successfully demonstrate the safety and efficacy of its product candidates; whether Magenta’s cash resources will be sufficient to fund Magenta’s foreseeable and unforeseeable operating expenses and capital expenditure requirements; and risks, uncertainties and assumptions regarding the impact of the continuing COVID-19 pandemic on Magenta’s business, operations, preclinical activities, clinical trials, strategy, goals and anticipated timelines. These and other risks are described in additional detail in Magenta’s Quarterly Report on Form 10-Q for the quarter ended September 30, 2022, expected to be filed on or about November 3, 2022, and its other filings made with the Securities and Exchange Commission from time to time. Any forward-looking statements contained in this press release represent Magenta’s views only as of today and should not be relied upon as representing its views as of any subsequent date. Magenta explicitly disclaims any obligation to update any forward-looking statements, except to the extent required by law. Contact: Jill Bertotti, Real Chemistry (advisor to Magenta) 714-225-6726 jbertotti@realchemistry.com Magenta Therapeutics, Inc. STATEMENTS OF OPERATIONS (unaudited) (In thousands, except share and per share data) Three Months Ended September 30, Nine Months Ended September 30, 2022 2021 2022 2021 Operating expenses: Research and development $ 11,201 $ 10,795 $ 39,351 $ 33,652 General and administrative 6,052 7,450 19,819 20,900 Total operating expenses 17,253 18,245 59,170 54,552 Loss from operations (17,253 ) (18,245 ) (59,170 ) (54,552 ) Interest and other income, net 1,190 818 2,886 2,708 Net loss $ (16,063 ) $ (17,427 ) $ (56,284 ) $ (51,844 ) Net loss per share, basic and diluted $ (0.27 ) $ (0.30 ) $ (0.95 ) $ (0.97 ) Weighted average common shares outstanding, basic and diluted 59,269,965 58,583,476 58,963,280 53,655,314 BALANCE SHEET DATA (unaudited) (In thousands) September 30, 2022 December 31, 2021 Cash, cash equivalents and marketable securities $ 128,284 $ 176,926 Working capital 119,176 169,830 Total assets 164,123 189,934 Stockholders' equity 124,025 172,672