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LOS ANGELES--( BUSINESS WIRE )--Researchers from City of Hope ® , one of the largest and most advanced cancer research and treatment organizations in the United States, whose Los Angeles comprehensive cancer center is ranked among the nation’s top 5 cancer centers by U.S. News & World Report, presented new study results on treatment options, side effect prevention and risk prediction for blood cancer patients at this year’s ASH conference in San Diego, California, held Dec. 7 to 10. Scientists and physicians discussed outcomes for clinical trials and studies that investigated immunotherapies, like CAR T cell therapy and monoclonal antibodies, in understudied and rare blood cancer types, graft-versus-host disease, prevention strategies for donor stem cell transplant patients, a new risk assessment model for older transplant recipients and more. “The work presented by City of Hope experts at this year’s conference showcases our commitment to comprehensive, patient-centered cancer care and research that includes rare and difficult blood cancer subtypes and other patient populations that are often overlooked in clinical trials,” said Eileen Smith , M.D., City of Hope’s Francis & Kathleen McNamara Distinguished Chair in Hematology & Hematopoietic Cell Transplantation. “Studies in supportive care and better risk prediction models add depth to our groundbreaking translational work in new treatment options.” Highlighting City of Hope’s leadership in treatment and research of blood cancers and related diseases, its experts will present or contribute to more than 104 sessions, including 35 oral sessions, 56 poster sessions, 13 scientific symposia, scientific workshops and educational programs. Highlights of their novel work include: Updating results for revumenib study in acute leukemias Roughly 10% of patients with acute leukemias have a certain mutation known as rearrangement in the lysine methyltransferase 2A (KMT2Ar) gene. This change in the gene is associated with a poor prognosis. Ibrahim Aldoss , M.D., City of Hope associate professor in the Division of Leukemia, reported on findings from a phase 2 study aimed at targeting a protein interaction with a therapy called revumenib for the treatment of patients with relapsed and therapy-resistant KMT2Ar acute leukemia. “In this updated pivotal phase 2 analysis, revumenib continues to consistently provide clinically meaningful responses in heavily pretreated patients with relapsed or refractory KMT2Ar acute leukemias, including high rates of complete remission and the ability to proceed to blood stem cell transplants,” said Dr. Aldoss. Previously reported interim data from the clinical trial, one of the most significant abstracts presented at the ASH conference in 2023, had shown that revumenib — a potent oral therapy that inhibits a scaffolding protein called menin, which plays a key role in the development of leukemia — had a tolerable safety profile and a high rate of complete remission. Dr. Aldoss’s 2024 ASH presentation included results from a longer follow-up timeline and a larger data set. The trial enrolled 116 heavily pretreated patients, representing the largest evaluation of menin inhibition in people with relapsed or resistant KMT2Ar acute leukemia, including the largest pediatric menin inhibitor cohort to date. The safety arm of the trial included all participants and showed that revumenib is manageable. For the efficacy cohort, including 97 patients, 62 (64%) responded with 22 (23%) attaining complete or complete remission with partial hematologic recovery (CR+CRh). At the time of the interim analysis, 13 patients had achieved CR+CRh, and with seven additional months of follow-up, the updated median duration of CR+CRh in these responders was 13 months. “Our study led to the recent FDA approval for patients with relapsed or refractory KMT2Ar acute leukemia,” said Dr.. Aldoss. “We are thrilled that our work means these high-risk patients now have access to an effective therapeutic option.” Early application of CAR T cell therapy as a curative treatment in older adults with B-ALL Dr. Aldoss also reported on preliminary results of a trial investigating the use of CD19 CAR T cell therapy in older patients with B cell acute lymphoblastic leukemia (B-ALL), a fast-growing and aggressive cancer. People 55 years or older who develop B-ALL often have poor outcomes due to both the disease’s propensity to come back or be therapy-resistant and limited tolerability of curative modalities, like stem cell transplants. To see if a City of Hope-developed CD19 CAR T cell therapy could offer a curative option for older B-ALL patients who had achieved a complete response to a frontline therapy but remained at-risk for relapse due to the biology of the disease, Dr. Aldoss and a study team have treated 13 patients with CD19 CAR T cells in a pilot, nonrandomized trial . They hypothesize that administering of single infusion of CAR T during remission could result in low rates of toxicity and offer potential cure without the need for additional cycles of therapy. So far, their hypothesis has held true, according to Dr. Aldoss. The therapy was shown to be tolerable and safe, and the patients have maintained their walking speed and cognitive function post-infusion, and returned back to their regular lifestyle early. CD19CAR T cells expanded adequately and persisted for up to nine months post-infusion. These preliminary results indicate a durable remission for patients after receiving an infusion. “Once our favorable results are validated in a larger confirmatory study this may change the treatment paradigm of older adults with B-ALL who otherwise do poorly with current therapeutic strategies,” said Dr. Aldoss. Evaluating CAR T cell therapy for a high-risk non-Hodgkin lymphoma Patients with transformed indolent non-Hodgkin lymphoma (tiNHL) are a high-risk patient population historically associated with poor outcomes when using conventional therapies. Now, a multicenter retrospective study led by Swetha Kambhampati Thiruvengadam , M.D, assistant professor in the Division of Lymphoma, has evaluated the real-world use of a chimeric antigen receptor (CAR) T cell therapy for this group of patients. CD19 chimeric antigen receptor (CAR) T cell therapy has revolutionized the treatment landscape of B cell lymphoma. By genetically altering patients’ T cells in the lab, scientists can program the immune cells to seek and destroy cancer cells with the CD19 antigen, which is found on B cell lymphomas, including tiNHL. The treatment is approved for people with tiNHL, but they were underrepresented in pivotal clinical trials that established CD19 CAR T cell therapy as an effective treatment for B cell cancers. “This is the largest study to our knowledge evaluating outcomes of CD19 CAR T for transformed indolent non-Hodgkin lymphoma patients compared to de novo aggressive large B cell lymphoma in the real-world setting,” said Dr. Thiruvengadam. The multicenter, retrospective study included 1,182 patients who had received CD19 CAR T cell therapies for two types of cancer: 338 tiNHL patients and 884 patients in the de novo aggressive large B cell lymphoma (aLBCL) comparison group. The results demonstrated that patients with tiNHL have higher complete response rates and may have lower risk of death or relapse/progression than those with de novo aLBCL. Patients in the tiNHL cohort also had a more favorable toxicity profile compared to de novo aLBCL. “Our study suggests CD19 CAR T is a highly effective and safe treatment option for patients with tiNHL and may overcome the historically poor prognosis in this population,” said Dr. Thiruvengadam. “It also suggests that these patients would be good candidates for clinical trials that move CAR T cell therapy to earlier lines of therapy, both because of poor expected outcomes with chemoimmunotherapy and because of excellent outcomes with CAR T.” This study was nominated for a “Best of ASH” award, which highlights the most leading-edge science presented in oral abstracts at the conference. Finding an effective therapy for rare types of lymphoma Cytotoxic T cell lymphomas (CTL) are a group of lymphomas that are very rare and have no standard treatment of care. Due to their rarity, very few patients with cytotoxic T cell lymphomas are included in clinical trials, meaning very little data exists regarding the efficacy of known T cell lymphoma therapies for this population. But a recently launched clinical trial led by Jasmine Zain , M.D., director of the T Cell Lymphoma Program and professor of hematology and hematopoietic stem cell transplantation, puts these CTL patients — for which there are five subtypes — front and center. And results from phase 1 of the phase 1/2 study testing a novel anti-CD94 monoclonal antibody are promising. “This is a first time that there is a therapy that could be effective for these rare lymphomas and may change the treatment landscape of these diseases,” said Dr. Zain. “As investigators, we now have the space to focus on these diseases that are usually fatal for patients and for which there are currently no treatments.” CD94 is a molecule that arises from cytotoxic T cells and is expressed on rare T cell lymphomas. The clinical trial tested the safety and efficacy of a next-generation therapeutic antibody called DR-01 that targets CD94. When the antibody binds to CD94 on the cancer cells, it engages natural killer cells to destroy the lymphoma. In the safety cohort of 39 CTL patients, there were no dose-limiting toxicities, and the only significant treatment-related adverse event observed was an infusion-related reaction that was managed with supportive measures. In the efficacy group of 21 patients, the overall response rate was 33%, with three complete responses in which two of the patients went on to receive a potentially curative stem cell transplant. “These results are very promising for patients,” said Dr. Zain. “This trial is for relapsed and refractory patients, but if it is successful, then we may be able to study it either alone or in combinations in the upfront setting and move the needle towards curing these patients.” Improving outcomes for cutaneous T cell lymphomas Cutaneous T cell lymphomas (CTCL) are rare, aggressive, incurable types of cancer that cause itchy, disfiguring skin conditions impacting patients’ quality of life. Patients with therapy-resistant or advanced CTCL have poor prognoses and few treatment options. Which is why Christiane Querfeld , M.D., Ph.D., director of the Cutaneous Lymphoma Program at City of Hope’s Toni Stevenson Lymphoma Center, is searching for new ways to treat the disease. Dr. Querfeld recently led a phase 1/2 trial investigating whether adding an immune booster called lenalidomide — typically used to treat multiple myeloma — to durvalumab, an immune checkpoint inhibitor to treat relapsed and/or resistant CTCL, would improve outcomes for CTCL patients. Findings from phase 2 of the study suggest that, when combined, the two therapies harness the body’s immune system to attack cancerous cells more potently than durvalumab alone. “This combined treatment demonstrated superiority to single-agent durvalumab and showed unparalleled responses relative to FDA-approved therapies, producing the most encouraging outcomes we have seen in our long experience of treating CTCL,” said Dr. Querfeld, who is also a professor in dermatology and dermatopathology at City of Hope. “It’s particularly exciting to note that these positive results were also seen in a subset of Black patients, who have a significantly increased risk of developing CTCL with worse outcomes.” A total of 25 patients who had failed at least two prior treatments were enrolled in the trial and randomized: 12 received durvalumab and 13 received a combination of durvalumab and lenalidomide. The overall response rate was 42% in patients who just received durvalumab and 75% in those who received the combination treatment. Similarly, progression-free survival at the one-year mark was 36% for the single agent cohort and 73% in the combination cohort. Responses were durable and ongoing, and the treatment was well tolerated. “This proposed immunotherapeutic strategy could provide CTCL patients with a more effective treatment for a disease that is currently incurable and in which standard approved treatments only achieve short durations of responses,” said Dr. Querfeld. “Furthermore, the knowledge gained from this study may be used to develop novel treatments not only for those with CTCL but for many other cancers.” Developing a new transplant risk-assessment model for older adults For many patients with high-risk blood cancers, hematopoietic cell transplantation (HCT), also known as bone marrow/blood stem cell transplants, are the only treatment options for long-term disease control. The older the patient, though, the higher the risk for transplant-related death. A team of researchers have now developed a model to better predict allogenic HCT outcomes in patients 60 years or older . “CHARM is a new score based on patient health information that predicts toxicities and degree of recovery after transplantation in older patients,” said Andrew Artz , M.D., M.S., a professor in the Division of Leukemia and senior author of a study outlining the model’s capabilities that was presented at ASH. “By using CHARM to assess risk, older patients who are likely to have fewer complications and better function after transplant will be more likely to be offered a potentially curative transplant.” CHARM assigns a total score for seven health variables: increasing age, lower albumin, higher C-reactive protein, higher percent of weight loss over the preceding year, lower patient-reported performance status scores, lower cognitive score per Montreal Cognitive Assessment and higher hematopoietic cell transplantation-specific comorbidity index (HCT-CI) scores. HCT-CI summarizes comorbid conditions aside from the primary disease. Originally developed to predict risks of nonrelapse mortality, the researchers wanted to assess CHARM’s ability to predict functional trajectories and morbidity after allogenic HCT in older patients. They enrolled 1,226 HCT candidates (ages 60+) from 49 centers in the United States to take the assessment and followed up on 1,105 patients who received the transplants. Among the HCT recipients, high CHARM scores predicted worse frailty, disability, cognitive decline and serious organ toxicities, all of which are critically important to older recipients of HCT. CHARM succeeds at informing patients and clinicians of transplant morbidity risks, which are separate from risks of developing acute graft-versus-host disease, the most common complication in donor HCT recipients. According to Dr. Artz and the other researchers, the study results support adopting CHARM in practice to counsel patients, expedite HCT referrals for lower risk patients and design trials to address the needs of high-CHARM-score patients. The Aging and Blood Cancers Program facilitated the high enrollment at City of Hope as one of many initiatives to advance transplant and cellular therapy outcomes in older adults. Assessing potential for engineered T cell therapies to reduce relapse in transplant patients In preparation for a hematopoietic cell transplantation (HCT), or bone marrow transplant for blood cancers, a patient’s own bone marrow cells must be destroyed. But for many older or less healthy individuals, a treatment regimen called reduced intensity conditioning (RIC) that uses lower doses of chemotherapy or radiation to prepare a patient for a bone marrow transplant is often more appropriate. However, disease relapse affects nearly 40% of this patient population — due to residual disease that RIC doesn’t eliminate — and is the leading cause of death. To reduce relapse rates, a group of researchers led by Monzr M. Al Malki , M.D., director of the unrelated donor bone marrow transplant and haploidentical transplant programs at City of Hope, is currently testing donor-derived T cell receptor engineered T cells designed to eliminate residual disease cells after transplantation in clinical trial called ALLOHA . “Early trial results show that the treatment is safe and tolerable,” said Dr. Al Malki. “Only 8% of all participants who received the engineered T cells relapsed compared to 35% relapsing on the control arm, showing the potential of the therapy to extend lives in high-risk populations.” ALLOHA is investigating the use of TSC-100 and TSC-1001, donor-derived T cell receptor engineered T cells that target HA-1 and HA-2 antigens, respectively, which are only expressed on bone marrow stem cells of HLA-A*02:01-positive patients. By choosing donors who are negative for the same target, this therapy can eliminate residual patient stem cells post-transplant while sparing donor-derived cells, thereby preventing relapse. Developed by TScan Therapeutics, Inc., a clinical-stage biotechnology company, TSC-100 and TSC-1001 were administered to 22 patients with either acute myeloid leukemia, acute lymphoblastic leukemia, or myelodysplastic syndrome which are the most common indication for transplantation. A control arm of 13 patients received the standard of care RIC HCT with no follow-up treatment. No dose-limiting toxicities were reported among the group receiving treatment and side effects encountered were similar in the treatment arm and control arm indicating the safety profile. The multicenter trial is ongoing, and enrollment continues. Targeting disease-initiating cells in acute myeloid leukemia In acute myeloid leukemia (AML) cells, a protein called cytoplasmic proliferating cell nuclear antigen (PCNA) is highly expressed, especially in leukemia stem cells, where it supports their growth. HyunJun Kang, Ph.D., a staff scientist in the City of Hope’s Department of Hematologic Malignancies Translational Science, and his colleagues conducted the study in their lab using the novel PCNA inhibitor AOH1996 — developed by researchers in the lab of Linda Malkas, Ph.D., the M.T. & B.A. Ahmadinia Professor in Molecular Oncology — to treat AML by reducing the energy production of leukemia stem cells, effectively slowing tumor growth and diminishing their numbers. “AOH1996, the PNCA inhibitor, represents a highly selective and innovative therapeutic approach for acute myeloid leukemia,” said Dr. Kang. “Effectively reducing leukemia stem cells can eliminate the disease and prevent reoccurrence. And, importantly, AOH1996 spares normal hematopoietic stem cells, emphasizing its safety and specificity.” The research team tested AOH1996 in animal models of AML, showing that the therapy effectively inhibits cancer cell growth and induces DNA damage in multiple cancer cells with minimal toxicity. Additionally, when combined with an existing, FDA-approved cancer medication called venetoclax, AOH1996 showed enhanced efficacy and improved survival in the animal models. While AOH1996 is in clinical trials for solid tumors, the team plans to develop a clinical trial to assess the combination of AOH1996 with venetoclax in patients with AML. “By selectively targeting leukemia stem cells while sparing normal blood stem cells, AOH1996 offers a promising therapeutic option with fewer off-target effects,” said Le Xuan (Truong) Nguyen, Ph.D., an assistant professor in City of Hope’s Department of Hematology & Hematopoietic Cell Transplantation and the study’s senior author. “The demonstrated efficacy in preclinical models suggest that a combination of AOH1996 and venetoclax could provide a powerful and well-tolerated strategy for patients with relapsed or refractory AML, ultimately improving survival rates and reducing the likelihood of relapse.” Preventing graft-versus-host disease in stem cell transplant patients Graft-versus-host-disease, or GVHD, is the most common complication for patients receiving stem cell transplants from a donor for blood cancers. According to results from a clinical trial led by Haris Ali , M.D. associate professor in the Division of Leukemia, adding a potent anti-inflammatory therapy to a standard GVHD prophylaxis may improve GVHD-free, relapse-free survival for transplant recipients. GVHD develops when donated cells attack a patient’s own tissues and can cause a variety of symptoms ranging from mild to life-threatening. In a phase 2a clinical trial, Dr. Ali and his colleagues tested the efficacy of a combination of the standard therapy to prevent GVHD, immunosuppression therapies tacrolimus and sirolimus, with itacitinib, a Janus kinases-1 inhibitor, which help reduce the body’s inflammatory response. (Previously reported early results of the trial had shown the combination to be safe and tolerable.) A total of 59 patients with acute leukemias, myelodysplastic syndrome or myelofibrosis who underwent hematopoietic stem cell transplants from matched donors received the combination GVHD prophylaxis. At one- and two-years post-transplant, GVHD-free, relapse-free survival was 54% and 40%, respectively. The historical rate of GVHD-free, relapse-free survival at one year is 30%. “This novel GVHD prophylaxis markedly improves GVHD-free, relapse-free survival by significantly reducing acute GVHD, a key cause of transplant related mortality and morbidity,” said Dr. Ali. “We hope to refine tapering strategies of the combination to further increase the length of GVHD-free, relapse-free survival timelines.” About City of Hope City of Hope's mission is to make hope a reality for all touched by cancer and diabetes. Founded in 1913, City of Hope has grown into one of the largest and most advanced cancer research and treatment organizations in the U.S., and one of the leading research centers for diabetes and other life-threatening illnesses. City of Hope research has been the basis for numerous breakthrough cancer medicines , as well as human synthetic insulin and monoclonal antibodies. With an independent, National Cancer Institute-designated comprehensive cancer center that is ranked top 5 in the nation for cancer care by U.S. News & World Report at its core, City of Hope’s uniquely integrated model spans cancer care, research and development, academics and training, and a broad philanthropy program that powers its work. City of Hope’s growing national system includes its Los Angeles campus, a network of clinical care locations across Southern California, a new cancer center in Orange County, California, and cancer treatment centers and outpatient facilities in the Atlanta, Chicago and Phoenix areas. City of Hope’s affiliated group of organizations includes Translational Genomics Research Institute and AccessHope TM . For more information about City of Hope, follow us on Facebook , X , YouTube , Instagram and LinkedIn .

Company to present poster on initial data from heme malignancies Phase 1 trial at the 65th ASH Annual Meeting and Exposition; Company to host virtual KOL event on Monday, December 11, 2023, at 8:00 a.m. ET Announced recent FDA clearance of IND for TSC-203-A0201 targeting PRAME Presented six posters at the SITC 38th Annual Meeting, highlighting solid tumor Phase 1 trial design and addition of melanoma-associated antigen C2 (MAGE-C2) to ImmunoBank Ended Q3 with cash, cash equivalents, and marketable securities of $215.4 million, funding operations into 2026 WALTHAM, Mass., Nov. 09, 2023 (GLOBE NEWSWIRE) -- TScan Therapeutics, Inc. (Nasdaq: TCRX), a clinical-stage biopharmaceutical company focused on the development of T cell receptor (TCR)-engineered T cell therapies (TCR-T) for the treatment of patients with cancer, today reported financial results and provided a corporate update for the third quarter ended September 30, 2023. “During the third quarter we made meaningful progress across both our heme and solid tumor programs and plan to share initial results from our heme program on six to eight patients treated with TCR-T, as well as several control arm patients, at the ASH Annual Meeting in December,” said Gavin MacBeath, Ph.D., Chief Executive Officer. “With the recent FDA clearance of our IND for TSC-203-A0201 targeting PRAME, we remain committed to populating the ImmunoBank with TCRs that address different targets and HLA types to expand the reach of multiplexed TCR-T cell therapy. We are currently on track to file two additional INDs by the end of the year and further expand the ImmunoBank in 2024. TScan is funded to execute on upcoming anticipated milestones into 2026, by which time we expect to have duration of response data for patients treated with multiplex therapy in the solid tumor program and two-year relapse data for patients in the heme program.” Recent Corporate Highlights TScan will present a poster at the 65th American Society of Hematology (ASH) Annual Meeting and Exposition taking place in San Diego, CA, and online, December 9–12, 2023: Title: Initial Results of a Phase 1 Trial of TSC-100 and TSC-101, Engineered T Cell Therapies That Target Minor Histocompatibility Antigens to Prevent Relapse after Allogeneic Hematopoietic Cell TransplantationAuthors: Monzr Al Malki, Alla Keyzner, Hyung C. Suh, Aasiya Matin, Erica Buonomo, Yun Wang, Nina Abelowitz, Jim Murray, Gavin MacBeath, Debora Barton, Shrikanta Chattopadhyay, Ran ReshefPublication Number: 2090Session Name: 704. Cellular Immunotherapies: Early Phase and Investigational Therapies: Poster ISession Date & Time: Saturday, December 9, 2023; 5:30–7:30 p.m. PTLocation: San Diego Convention Center, Halls G-H The Company will host a virtual KOL event featuring Monzr M. Al Malki, M.D., on Monday, December 11, 2023, at 8:00 a.m. ET to discuss the data presented at ASH. Dr. Al Malki is an Associate Professor in the Department of Hematology & Hematopoietic Cell Transplantation and Director of the Unrelated Donor Bone Marrow Transplant and Haploidentical Transplant Programs at City of Hope. Details for attending the event can be found here. During the third quarter, TScan announced U.S. Food and Drug Administration (FDA) clearance of its investigational new drug (IND) application for TSC-203-A0201, a TCR-T targeting PReferentially expressed Antigen in MElanoma (PRAME). TSC-203-A0201 is TScan’s fourth TCR-T cell product cleared for use in its solid tumor program.This month, TScan presented six posters at the Society for Immunotherapy of Cancer (SITC) 38th Annual Meeting. Notable highlights include TScan’s solid tumor Phase 1 trial design supporting a separate screening protocol to identify patients ahead of disease progression, and the disclosure of the previously undisclosed target of TSC-201-B0702 as MAGE-C2. Copies of the presentation materials can be found on the “Publications” section of the Company’s website at www.tscan.com. Upcoming Anticipated Clinical Milestones Heme Malignancies Program: TScan’s two lead TCR-T cell therapy candidates, TSC-100 and TSC-101, are designed to target HA-1 and HA-2, respectively, to treat residual disease and prevent relapse in acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL) and myelodysplastic syndromes (MDS) patients undergoing allogeneic haploidentical hematopoietic cell transplantation (HCT) with reduced intensity conditioning (RIC). (NCT05473910) Expects to reach the recommended Phase 2 dose for both TSC-100 and TSC-101 and report interim clinical data for the program by the end of 2023.Plans to complete Phase 1 dosing and report prevention of relapse data in 2024. Solid Tumor Program: TScan remains committed to populating the ImmunoBank, its collection of therapeutic TCRs across novel and validated targets as well as different HLA types, to overcome tumor heterogeneity and address resistance that can arise from HLA loss with multiplexed therapy. Anticipates further expansion of the ImmunoBank with IND filings for two additional TCR-Ts by year-end 2023.Plans to initiate Phase 1 solid tumor clinical study and enroll the first patient by year-end 2023.Expects to report initial multiplexed therapy data for its first combinations of TCR-Ts under T-Plex, as well as response data for singleplex cohorts, in 2024. Third Quarter 2023 Financial Results As of September 30, 2023, TScan Therapeutics had cash, cash equivalents, and marketable securities of $215.4 million, excluding $5.0 million of restricted cash. Based on current operating plans, the Company believes that existing cash, cash equivalents, and marketable securities will be sufficient to fund its operating expenses and capital expenditure requirements into 2026. Revenue for the third quarter ended September 30, 2023, was $3.9 million, compared to $3.4 million for the third quarter ended September 30, 2022 (2022 Quarter). This increase is primarily due to timing of research activities related to the collaboration agreement with Amgen in the second quarter of 2023 versus timing of research activities related to a collaboration and license agreement with Novartis Institutes for Biomedical Research, Inc. in the 2022 Quarter. Research and development expenses for the third quarter ended September 30, 2023, were $22.7 million, compared to $15.0 million for the 2022 Quarter. The increase of $7.7 million was primarily driven by increased costs associated with clinical trial start-up fees and patient enrollment, increased personnel costs, and expansion of facilities. General and administrative expenses for the third quarter ended September 30, 2023, were $5.9 million, compared to $4.9 million for the 2022 Quarter. The increase of $1.0 million in general and administrative expenses was primarily driven by increased legal and professional fees. For the third quarter ended September 30, 2023, TScan Therapeutics reported a net loss of $23.0 million, compared to a net loss of $16.2 million for the 2022 Quarter. As of September 30, 2023, the Company had issued and outstanding shares of 47,823,116, which consists of 43,546,528 shares of voting common stock and 4,276,588 shares of non-voting common stock, and outstanding pre-funded warrants to purchase 47,010,526 shares of voting common stock at an exercise price of $0.0001 per share. About TScan Therapeutics, Inc. TScan is a clinical-stage biopharmaceutical company focused on the development of T cell receptor (TCR)-engineered T cell therapies (TCR-T) for the treatment of patients with cancer. The Company’s lead TCR-T therapy candidates, TSC-100 and TSC-101, are in development for the treatment of patients with hematologic malignancies to eliminate residual disease and prevent relapse after allogeneic hematopoietic cell transplantation. The Company is also developing multiplexed TCR-T therapy candidates for the treatment of various solid tumors. The Company has developed and continues to build its ImmunoBank, the Company’s repository of therapeutic TCRs that recognize diverse targets and are associated with multiple HLA types, to provide customized multiplexed TCR-T therapies for patients with a variety of solid tumors. Forward-Looking Statements This release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, including, but not limited to, express or implied statements regarding the Company’s plans, progress, and timing relating to the Company’s hematologic malignancies program, including reaching recommended Phase 2 dose for TSC-100 and TSC-101, reporting interim clinical data, completing Phase 1 dosing, and reporting prevention of relapse data; the Company’s plans, progress, and timing relating to the Company’s solid tumor programs, including expanding the ImmunoBank, submitting of INDs, initiating clinical trials, and reporting data; the Company’s ability to fund its operating expenses and capital expenditure requirements with its existing cash and cash equivalents; the Company’s current and future research and development plans or expectations; the structure, timing and success of the Company’s planned preclinical development, submission of INDs, and clinical trials; the potential benefits of any of the Company’s proprietary platforms, multiplexing, or current or future product candidates in treating patients; the Company’s beliefs about operating expenses and that it will have capital to fund the Company into 2026; and the Company’s goals and strategy. TScan intends such forward-looking statements to be covered by the safe harbor provisions for forward-looking statements contained in Section 21E of the Securities Exchange Act of 1934 and the Private Securities Litigation Reform Act of 1995. In some cases, you can identify forward-looking statements by terms such as, but not limited to, “may,” “might,” “will,” “objective,” “intend,” “should,” “could,” “can,” “would,” “expect,” “believe,” “anticipate,” “project,” “target,” “design,” “estimate,” “predict,” “potential,” “plan,” “on track,” or similar expressions or the negative of those terms. Such forward-looking statements are based upon current expectations that involve risks, changes in circumstances, assumptions, and uncertainties. The express or implied forward-looking statements included in this release are only predictions and are subject to a number of risks, uncertainties and assumptions, including, without limitation: the beneficial characteristics, safety, efficacy, therapeutic effects and potential advantages of TScan’s TCR-T therapy candidates; TScan’s expectations regarding its preclinical studies being predictive of clinical trial results; the timing of the initiation, progress and expected results of TScan’s preclinical studies, clinical trials and its research and development programs; TScan’s plans relating to developing and commercializing its TCR-T therapy candidates, if approved, including sales strategy; estimates of the size of the addressable market for TScan’s TCR-T therapy candidates; TScan’s manufacturing capabilities and the scalable nature of its manufacturing process; TScan’s estimates regarding expenses, future milestone payments and revenue, capital requirements and needs for additional financing; TScan’s expectations regarding competition; TScan’s anticipated growth strategies; TScan’s ability to attract or retain key personnel; TScan’s ability to establish and maintain development partnerships and collaborations; TScan’s expectations regarding federal, state and foreign regulatory requirements; TScan’s ability to obtain and maintain intellectual property protection for its proprietary platform technology and our product candidates; the sufficiency of TScan’s existing capital resources to fund its future operating expenses and capital expenditure requirements and execute on upcoming anticipated milestones into 2026; and the effect of the COVID-19 pandemic, including mitigation efforts and political, economic, legal and social effects, on any of the foregoing or other aspects of TScan’s business or operations; and other factors that are described in the “Risk Factors” and “Management’s Discussion and Analysis of Financial Condition and Results of Operations” sections of TScan’s most recent Annual Report on Form 10-K and any other filings that TScan has made or may make with the SEC in the future. Any forward-looking statements contained in this release represent TScan’s views only as of the date hereof and should not be relied upon as representing its views as of any subsequent date. Except as required by law, TScan explicitly disclaims any obligation to update any forward-looking statements. Contacts Heather SavelleTScan Therapeutics, Inc.VP, Investor Relations857-399-9840hsavelle@tscan.com Joyce AllaireLifeSci Advisors, LLCManaging Director617-435-6602jallaire@lifesciadvisors.com TScan Therapeutics, Inc.Condensed Consolidated Balance Sheet Data(unaudited, in thousands, except share amount) September 30,2023 December 31,2022Assets Cash and cash equivalents$155,193 $120,027 Other assets 136,186 79,064 Total assets$291,379 $199,091 Liabilities and Stockholders' Equity Total liabilities$122,418 $99,657 Total stockholders' equity 168,961 99,434 Total liabilities and stockholders' deficit$291,379 $199,091 Common stock outstanding as of September 30, 2023 47,823,116 TScan Therapeutics, Inc.Condensed Consolidated Statements of Operations(unaudited, in thousands, except share and per share amounts) Three Months Ended September 30, 2023 2022Revenue Collaboration and license revenue$3,887 $3,363 Operating expenses: Research and development 22,741 15,031 General and administrative 5,894 4,910 Total operating expenses 28,635 19,941 Loss from operations (24,748) (16,578)Interest and other income, net 2,733 534 Interest expense (982) (201)Net loss$(22,997) $(16,245)Net loss per share, basic and diluted$(0.24) $(0.67)Weighted average common shares outstanding—basic and diluted 94,829,844 24,073,935

Poster highlights Phase 1 results following treatment with TSC-100 and TSC-101 after hematopoietic cell transplantation Company to host a virtual KOL event featuring Monzr M. Al Malki, M.D., to discuss highlights from the meeting and preliminary data today, Wednesday, May 17th at 5:30 p.m. ET WALTHAM, Mass., May 17, 2023 (GLOBE NEWSWIRE) -- TScan Therapeutics, Inc. (Nasdaq: TCRX), a clinical-stage biopharmaceutical company focused on the development of T cell receptor (TCR)-engineered T cell therapies (TCR-T) for the treatment of patients with cancer, today announced a poster presentation highlighting preliminary data from the Phase 1 umbrella clinical trial evaluating TSC-100 and TSC-101 targeting minor histocompatibility antigens (MiHA) HA-1 and HA-2, respectively, to treat residual disease and prevent relapse following hematopoietic cell transplantation (HCT) using reduced intensity conditioning (RIC) in patients with acute myeloid leukemia (AML), myelodysplastic syndromes (MDS), or acute lymphocytic leukemia (ALL) at the American Society of Gene & Cell Therapy (ASGCT) 26th Annual Meeting 2023. TScan has developed two lead TCR-T cell therapy candidates, TSC-100 and TSC-101, that express TCRs targeting MiHAs HA-1 and HA-2, respectively, both presented by HLA-A*02:01. The goal is to select HCT patients who are HA-1 or HA-2 positive, with donors who are mismatched on either the MiHA or HLA-A*02:01. In this context, TSC-100 and TSC-101 are designed to eliminate all recipient hematopoietic cells, including malignant cells, that persist post-transplant, while leaving donor-derived cells unaffected. Both products are being developed in patients with AML, ALL, and MDS undergoing allogeneic haploidentical HCT with RIC, with the goal of preventing disease relapse. Approximately 42% of patients with these diseases relapse within two years of RIC transplant, at which point there are limited treatment options and poor prognosis. The longer-term objective is to enable more patients to maintain prolonged remission after receiving HCT with RIC, which is a more tolerable conditioning regimen than myeloablative conditioning. “We continue to make meaningful progress in our Phase 1 umbrella trial with preliminary data presented at ASGCT demonstrating notable differences following treatment with both of our TCR-T cell therapy candidates,” said Debora Barton, M.D., Chief Medical Officer. “In a p53-mutated MDS patient who received TSC-101 infusion, we observed T cell expansion between 14 and 21 days post-treatment and observed markers of T cell activation and proliferation. Particularly encouraging, this patient had 100% donor chimerism post-transplant with no detectable patient-derived hematopoietic cells with sensitivity limit of 0.13%, and no dose-limiting toxicities. Our Phase 1 study is rapidly enrolling and TSC-101 is advancing into the second dose level. We are on track to reach the recommended Phase 2 dose for TSC-100 and TSC-101 and report interim clinical data for the program by the end of 2023.” Gavin MacBeath, Ph.D., acting Chief Executive Officer and Chief Scientific and Operating Officer added: “We are very excited to progress to the second dose level for TSC-101 after seeing encouraging results from the patient at this first dose level. We are hopeful to continue to produce robust clinical outcomes as we progress our Phase 1 trial and remain excited about the potential clinical benefits our engineered T cells may have in difficult-to-treat patient populations.” The Phase 1 umbrella trial is a multi-arm, i3+3 study evaluating TSC-100, TSC-101, and standard of care HCT alone (control arm) in patients with AML, ALL or MDS. Patients enrolled in Dose Level 1 (DL1) receive either TSC-100 or TSC-101 upon count recovery after HCT at approximately day 21. Patients enrolled in Dose Level 2 (DL2) will receive the same dose of TSC-100 or TSC-101 approximately 21 days post-transplant, followed by a second dose administered 40 days after the initial dose, provided there are no safety issues. The trial design also includes a third dose level (DL3), where the second dose is escalated 4-fold. Key Poster Highlights: Phase 1 umbrella clinical trial evaluating TSC-100 and TSC-101 targeting MiHAs HA-1 and HA-2, respectively, to treat residual disease and prevent relapse following HCT using RIC in patients with AML, MDS or ALL Two control arm patients have been enrolled and received standard of care (SOC) (HCT alone): Both control arm patients have medium-risk MDS and experienced incomplete donor chimerism (presence of patient-derived cells) following transplant One patient is now in early stages of relapse: after 100 days, patient-derived cells are still observed and increasing TSC-101 treatment arm (n=1 high-risk MDS with p53 mutation): DL1 administered 21 days after transplant Engineered T cells showed expansion between 14-21 days after infusion Detectable markers of activation and proliferation observed Twenty-one days after treatment and 42 days after transplant, donor chimerism was at 100% (no detectable patient-derived hematopoietic cells with sensitivity limit of 0.13%) Minimal residual disease (MRD) assessment: p53 mutation was not detected post-transplant in bone marrow and peripheral blood samples, with sensitivity limit of 0.01% No DLTs observed Study advancing to DL2 TSC-100 treatment arm (n=1 T-cell ALL): DL1 administered 28 days after transplant T cell expansion occurred on Day 7 with detectable markers of T cell activation and proliferation Two assays are used to detect the action of T cells: MRD: SOC assays measuring remaining malignant cells use flow cytometry, which has a sensitivity of ~0.1% High sensitivity assay based on next-generation sequencing (NGS) and droplet digital PCR is also used in this study, with a sensitivity of 0.01% Chimerism: SOC STR assays have ~1% sensitivity Study is using the high-sensitivity NGS-based Alloheme assay, with a sensitivity of ~0.13% A copy of the poster can be accessed on the “Publications” section of the Company’s website at . Virtual KOL Event The Company will share highlights from its poster presented at ASGCT, featuring Monzer M. Al Malki, M.D, Associate Profession, Division of Leukemia, Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, on Wednesday, May 17th at 5:30 p.m. ET to discuss the presentation and results from the ongoing Phase 1 study of TSC-100 and TSC-101 to treat residual disease and prevent relapse following HCT using RIC in patients with AML, MDS and ALL. To register for the event, please click here. A replay will be available on the “Events and Presentations” section of the Company’s website at ir.tscan.com. About TScan Therapeutics, Inc. TScan is a clinical-stage biopharmaceutical company focused on the development of T cell receptor (TCR)-engineered T cell therapies (TCR-T) for the treatment of patients with cancer. The Company’s lead TCR-T therapy candidates, TSC-100 and TSC-101, are in development for the treatment of patients with hematologic malignancies to eliminate residual disease and prevent relapse after allogeneic hematopoietic cell transplantation. The Company is also developing multiplexed TCR-T therapy candidates for the treatment of various solid tumors. The Company has developed and continues to build its ImmunoBank, the Company’s repository of therapeutic TCRs that recognize diverse targets and are associated with multiple HLA types, to provide customized multiplexed TCR-T therapies for patients with a variety of solid tumors. Forward-Looking Statements This release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, including, but not limited to, express or implied statements regarding the Company’s plans, progress, and timing relating to the Company’s hematologic malignancies program, including patient enrollment, reaching recommended Phase 2 dose for TSC-100 and TSC-101, and interim clinical data; the structure, timing and success of the Company’s planned preclinical development and clinical trials; the potential benefits of any of the Company’s proprietary platforms, multiplexing, or current or future product candidates in treating patients; and the Company’s goals, focus, and strategy. TScan intends such forward-looking statements to be covered by the safe harbor provisions for forward-looking statements contained in Section 21E of the Securities Exchange Act of 1934 and the Private Securities Litigation Reform Act of 1995. In some cases, you can identify forward-looking statements by terms such as, but not limited to, “may,” “might,” “advance,” “will,” “objective,” “intend,” “should,” “could,” “can,” “would,” “expect,” “believe,” “anticipate,” “project,” “target,” “design,” “estimate,” “predict,” “potential,” “plan,” “on track,” or similar expressions or the negative of those terms. Such forward-looking statements are based upon current expectations that involve risks, changes in circumstances, assumptions, and uncertainties. The express or implied forward-looking statements included in this release are only predictions and are subject to a number of risks, uncertainties and assumptions, including, without limitation: the beneficial characteristics, safety, efficacy, therapeutic effects and potential advantages of TScan’s TCR-T therapy candidates; TScan’s expectations regarding its preclinical studies being predictive of clinical trial results; TScan’s approved INDs and enrollment of patients in its study being indicative or predictive of bringing TScan closer to its goal of providing customized TCR-T therapies to treat patients with cancer; the partnership with Amgen being indicative or predictive of the value of TScan’s target discovery platform outside of oncology; the timing of the launch, initiation, progress and expected results and announcements of TScan’s preclinical studies, clinical trials and its research and development programs; TScan’s timeline regarding its filing of INDs for its TCRs throughout the year, TScan’s ability to enroll patients for its clinical trials within its expected timeline, TScan’s plans relating to developing and commercializing its TCR-T therapy candidates, if approved, including sales strategy; estimates of the size of the addressable market for TScan’s TCR-T therapy candidates; TScan’s manufacturing capabilities and the scalable nature of its manufacturing process; TScan’s estimates regarding expenses, future milestone payments and revenue, capital requirements and needs for additional financing; TScan’s expectations regarding competition; TScan’s anticipated growth strategies; TScan’s ability to attract or retain key personnel; TScan’s ability to establish and maintain development partnerships and collaborations; TScan’s expectations regarding federal, state and foreign regulatory requirements; TScan’s ability to obtain and maintain intellectual property protection for its proprietary platform technology and our product candidates; the sufficiency of TScan’s existing capital resources to fund its future operating expenses and capital expenditure requirements; and other factors that are described in the “Risk Factors” and “Management’s Discussion and Analysis of Financial Condition and Results of Operations” sections of TScan’s most recent Annual Report on Form 10-K and any other filings that TScan has made or may make with the SEC in the future. Any forward-looking statements contained in this release represent TScan’s views only as of the date hereof and should not be relied upon as representing its views as of any subsequent date. Except as required by law, TScan explicitly disclaims any obligation to update any forward-looking statements. Contacts Heather Savelle TScan Therapeutics, Inc. VP, Investor Relations 857-399-9840 hsavelle@tscan.com Joyce Allaire LifeSci Advisors, LLC Managing Director 617-435-6602 jallaire@lifesciadvisors.com