Acute Lymphoblastic Leukemia

Researchers have shown that targeting a gene regulated by two cancer-fuelling proteins can kill cancerous cells and halt their growth in laboratory models of B-cell acute lymphoblastic leukemia (ALL). Researchers have found a new way to potentially treat one of the most common forms of acute lymphoblastic leukaemia. The study, led by WEHI and the Peter MacCallum Cancer Centre, was able to kill leukaemia cells in the lab and stop cancer cells from growing, after identifying two new proteins critical for the development of the aggressive disease. The findings could lead to enhanced treatment options in the future, with plans underway to develop a clinical trial based on the research. Around 5200 people are diagnosed with a form of leukaemia in Australia each year. An estimated 1500 of these cases are acute -- meaning the blood cancer appears suddenly and grows quickly. Blood cancers like leukaemia are notoriously difficult to treat in adults, with 50% of Australian patients relapsing after the first round of chemotherapy and subsequently becoming resistant to further treatments. Associate Professor Ashley Ng, a corresponding author on the paper, said this presented a unique treatment challenge for these blood cancers and highlighted the urgent need for new therapeutics. "About 135,000 people live with a blood cancer or blood disorder in Australia, with 16 people dying every day from the disease," Assoc Prof Ng, a WEHI researcher and clinical haematologist at the Peter MacCallum Cancer Centre and Royal Melbourne Hospital, said. "Despite the medical advancements made in the cancer field over the years, the incidence of blood cancer has grown by 47% in the past decade. "The best way to enhance treatment options for patients is to continually improve our understanding of how leukaemia cancers behave and what drives their growth. "Our new research has identified two proteins that are critical for the development of B-cell acute lymphoblastic leukaemia, expanding our knowledge into how these cancers can form. "By uncovering this new vulnerability in leukaemia formation, we hope to exploit the findings for therapeutic benefit and also apply them to other forms of the disease." The research is published in the journal Science Advances. Master regulators Assoc Prof Ng has spent over a decade researching a protein that regulates gene activity in the cell nucleus, known as ERG. Imbalances in this protein can lead to blood cancers, like acute lymphoblastic leukaemia. His previous research uncovered the protein's critical role in Down syndrome associated blood disease and normal blood cell function, including how B cells -- which are essential for producing antibodies to fight against infections -- develop. First author Dr Kira Behrens said the research team wanted to understand what other types of proteins ERG works with to fuel leukaemia development. "We looked at the proteins that control how specific genes switch 'on' or 'off' to analyse how normal B-cells -- and critically -- B-cell acute lymphoblastic leukaemia -- can develop," Dr Behrens said. "After analysing the genes regulated by ERG and another protein, c-MYC, we discovered that these proteins were actually the master regulators of several important pathways and processes within the leukaemia cell." Researchers then narrowed the list down to focus on one pathway essential for making proteins, known as ribosome biogenesis. This led the team to focus on targeting a key gene essential to this pathway, POL I, which is also controlled by these master regulator proteins. The gene helps direct an important cell growth and division process that can lead to the development of cancer if it goes awry. Dr Behrens said: "By targeting POL I with inhibitors, we were able to kill leukaemia cells and stop their growth in our pre-clinical and human tissue models." "This was a surprising, yet remarkable discovery, as we were able to unravel a new pathway and potential drug target that can hopefully be used in the fight against leukaemia in the future." The study also involved a collaboration with Associate Professor Elaine Sanij (St. Vincent's Institute of Medical Research) whose work focuses on targeting POL I and ribosome biogenesis in cancer therapy. "The findings show that a subset of aggressive acute lymphoblastic leukaemia exhibit a form of addiction to producing of ribosomes, the protein making molecular machinery," Assoc Prof Sanij said. "They render this aggressive leukaemia sensitive to POL I inhibitors which target ribosome production. "Altogether, our work highlights the importance of developing this new approach to cancer therapy to treat oncogene-driven cancers." Collaborative power One of the drugs used in the study to target POL I was an agent developed by the Peter MacCallum Cancer Centre. Professor Rick Pearson, former Associate Director of Laboratory Research at Peter Mac, said the team hopes to mimic the study in a future clinical trial to help patients with acute lymphoblastic leukaemia. "We worked with WEHI researchers to confirm our agent is effective in targeting POL I activity and demonstrated its potency in impeding the leukaemia cell growth and division. "These findings highlight the power of collaboration and the remarkable results that can be achieved when bringing together experts from across various areas. "We hope this research will translate into successful clinical trials and potentially offer doctors a new treatment option for patients with acute lymphoblastic leukaemia," Professor Pearson said. This research was supported by the German Research Foundation (Deutsche Forschungsgemeinschaft), the National Health and Medical Research Council (NHMRC), Cancer Council Victoria, National Stem Cell Foundation of Australia, the Leukaemia Foundation and Victorian Cancer Agency. The study, "ERG and c-MYC Regulate a Critical Gene Network in BCR::ABL1-Driven B-cell Acute Lymphoblastic Leukaemia," is published in Science Advances.

Therapeutic treatment with Auxora shown to hasten the recovery of kidney function and improve survival in a rat model of acute kidney injury (AKI) Preclinical results are consistent with clinical observations made with Auxora, supporting the KOURAGE trial in patients with severe AKI that will start enrolling in 2Q 2024 LA JOLLA, Calif., March 13, 2024 /PRNewswire/ -- CalciMedica Inc. (CalciMedica or the Company) (Nasdaq: CALC), a clinical-stage biopharmaceutical company focused on developing novel calcium release-activated calcium (CRAC) channel inhibition therapies for acute and chronic inflammatory and immunologic diseases, last evening presented data from preclinical studies of Auxora™ in acute kidney injury (AKI) at the 29th International Acute Kidney Injury and Continuous Renal Replacement Therapy Conference (AKI & CRRT) in San Diego, CA. David Basile, Ph.D., Professor of Anatomy, Cell Biology and Physiology at Indiana University, gave an oral and poster presentation entitled "The Store-Operated Calcium Channel Inhibitor Auxora Improves Renal Function Following Ischemia-Induced Acute Kidney Injury in Rats." "At AKI & CRRT, Prof. Basile discussed the most recent preclinical study of Auxora in an acute kidney injury model that used a treatment regimen of three daily doses of drug started six hours after ischemic injury, which resembles the dosing in our clinical protocol. The positive results from this study build on prior preclinical data and indicate that inhibiting Orai1 activity in an AKI model improves kidney function," said Kenneth Stauderman, Ph.D., Founder and Chief Scientific Officer of CalciMedica. "In rats with ischemic kidney injury akin to Stage 2 AKI, Auxora was shown to provide nearly complete recovery of kidney function, as evidenced by improved glomerular filtration rate (GFR) at 72 hours after injury, while placebo-treated animals showed little improvement in GFR. In rats with kidney injury akin to Stage 3 AKI, the rats treated with placebo died while those on Auxora survived and showed modest recovery of GFR. We are excited as these studies support clinical observations of Auxora that suggest the drug may be beneficial for AKI patients." AKI is a serious acute critical illness and denotes a sudden reduction in kidney function, or the organ's ability to clean and filter the blood, that results from a complication of critical illness. These animal model studies support observations from CalciMedica's clinical trials, particularly CARDEA, the Company's Phase 2 trial in patients with severe and critical COVID-19 pneumonia, where AKI was a relatively common co-morbidity or a common sequela of the disease. Compared to placebo-treated patients, Auxora-treated patients in CARDEA had lower levels of key biomarkers associated with kidney injury, lower incidence of treatment-emergent AKI and reduced mortality in those patients with decreased kidney function at the time of treatment. Additionally, previous preclinical studies conducted by CalciMedica and others suggest that Orai1 activity contributes to the activation and infiltration of pro-inflammatory Th17 cells in the kidney, which is associated with the development of AKI. CalciMedica has also shown that the active ingredient in Auxora, zegocractin, inhibits release of IL-17, which is a key pro-inflammatory cytokine from Th17 cells. "As we initiate KOURAGE, our Phase 2 trial of Auxora in severe AKI patients with associated acute hypoxemic respiratory failure, we are encouraged to have additional supporting data showing that Auxora has beneficial activity in animal models of AKI," said Sudarshan Hebbar, M.D., Chief Medical Officer of CalciMedica. "Patients randomized in KOURAGE will have Stage 2 and Stage 3 AKI, so the results from Prof. Basile's recent preclinical study, most notably the survival benefit, are particularly meaningful. Severe AKI in the presence of respiratory failure has a mortality of approximately 50% and we are heartened to see that Auxora has the potential for a positive impact on patients with this devastating disease." Data Presented at the AKI & CRRT Conference The data presented at AKI & CRRT was from a series of studies referred to as Study 1 and Study 2. In Study 1, AKI was induced in a rat model through ischemia reperfusion injury (I/R), a transient ligation of the renal artery, while control animals underwent sham-surgery. Within 30 minutes of injury, the animals were treated with a single intravenous infusion of either 16 mg/kg of Auxora or placebo over a period of 4 hours. GFR, an important indicator of kidney function, was evaluated at 24 hours post-injury. Study 2 evaluated recovery of kidney function following I/R similar to Study 1 but varying in intensity to mimic different severity of disease. In Study 2, GFR was measured 2-4 hours after injury but before treatment, and treatment with 16 mg/kg of Auxora or placebo was administered at 6, 24 and 48 hours post-injury, with GFR again evaluated at 72 hours. Results from Study 1 showed that at 24 hours post-injury, GFR was significantly higher in rats treated with Auxora 30 minutes after injury versus placebo (61%, p<0.05). Additionally, animals treated with Auxora showed a reduction in Th17 cells in the kidney of approximately 50% as compared to those treated with placebo. In Study 2, in a group of animals with initial GFR reductions of approximately 50%, similar to Stage 2 AKI, GFR at 72 hours was significantly greater in Auxora-treated animals as compared to placebo-treated animals (0.81±0.03 vs. 0.47±0.04 ml/min/100g respectively; p<0.001). In a group of animals with GFR reductions ≥66%, similar to Stage 3 AKI, placebo-treated rats experienced 100% mortality by 72 hours while Auxora-treated rats had no mortality at 72 hours and were stable, showing modest recovery of kidney function. These results indicate that Auxora has the ability to hasten the recovery of kidney function and improve survival in rat models of AKI. About AKI Acute kidney injury (AKI) denotes a sudden reduction in kidney function, or the organ's ability to clean and filter the blood, as measured by increased serum creatinine (a cellular waste product) or decreased urine volume. AKI can result as a complication of critical illness such as sepsis, pneumonia and acute pancreatitis, and other causes such as trauma, surgery and burns. There are approximately 3.7 million patients hospitalized with AKI in the United States each year. The majority have Stage 1 AKI and recover with supportive care alone. However, approximately 1.1 million of these patients advance to Stage 2 and Stage 3 AKI, over half of whom have associated acute hypoxemic respiratory failure (AHRF). The risk of serious morbidities and mortality is significant for advanced Stage 2 and Stage 3 AKI patients. There are currently no approved therapies for AKI. About KOURAGE KOURAGE is a randomized, double-blind, placebo-controlled study that will evaluate 150 patients with Stage 2 and 3 AKI who have AHRF and are receiving oxygen by non-invasive mechanical ventilation, high flow nasal cannula or intermittent mandatory ventilation (IMV). Patients will be stratified by classification of stage of AKI as well as the use of IMV. Patients will receive either a four-hour infusion of Auxora or placebo at 1.25 mL/kg as a first dose, after which they will receive Auxora or placebo at 1.0 mL/kg at hours 24, 48, 72 and 96. The primary endpoint of the trial will be evaluation of patients through day 30 to determine days alive, ventilator-free and dialysis-free. Secondary endpoints will include a composite of: all-cause mortality, decrease in estimated glomerular filtration rate (eGFR), and the incidence of dialysis over a period of 90 days, also known as MAKE-90 (Major Adverse Kidney Events at 90 days). About Auxora™ CalciMedica's lead clinical compound, Auxora™, is a potent and selective small molecule inhibitor of Orai1-containing CRAC channels that is being developed for use in patients with acute inflammatory and immunologic illnesses. CRAC channels are found on many cell types, including immune system cells, endothelium cells and pancreatic acinar cells, where aberrant activation of these channels may play a key role in the pathobiology of acute and chronic inflammatory syndromes. Auxora is currently being evaluated in: (i) a Phase 2b trial for acute pancreatitis (AP) with accompanying systemic inflammatory response syndrome (SIRS), called CARPO, (ii) an investigator-sponsored Phase 1/2 trial, called CRSPA, being conducted in pediatric patients with asparaginase-induced pancreatic toxicity (AIPT) as a side effect of pediatric acute lymphoblastic leukemia treatment with asparaginase, (iii) a Phase 2 dose-ranging pharmacodynamic study in critical COVID-19 patients and (iv) a Phase 2 trial in AKI with associated AHRF, called KOURAGE, expected to initiate in the first half of 2024. There are currently no approved therapies to treat either AP, AIPT or AKI. In previous trials, patients responded well to Auxora regardless of severity or cause of disease. CalciMedica is also exploring the potential of Auxora treatment for other acute indications including acute respiratory distress syndrome. About CalciMedica CalciMedica is a clinical-stage biopharmaceutical company focused on developing novel CRAC channel inhibition therapies for inflammatory and immunologic diseases. CalciMedica's proprietary technology targets the inhibition of CRAC channels to modulate the immune response and protect against tissue cell injury, with the potential to provide therapeutic benefits in life-threatening inflammatory and immunologic diseases for which there are currently no approved therapies. CalciMedica's lead product candidate Auxora™, a proprietary, intravenous-formulated CRAC channel inhibitor, has demonstrated positive and consistent clinical results in multiple completed efficacy clinical trials. CalciMedica is currently conducting a Phase 2b trial for a planned 216 patients (called CARPO – NCT04681066) for AP with SIRS, with topline data expected in the first half of 2024, as well as supporting the ongoing Phase 1/2 CRSPA AIPT study (called CRSPA – NCT04195347), with additional data expected by 2H 2024. CalciMedica plans to initiate its Phase 2 KOURAGE study in AKI in 1H 2024. CalciMedica was founded by scientists from Torrey Pines Therapeutics and the Harvard CBR Institute for Biomedical Research, and is headquartered in La Jolla, CA. For more information, please visit . Forward-Looking Statements This communication contains forward-looking statements which include, but are not limited to, statements regarding CalciMedica's planned and ongoing clinical trials and the timing, design, expected patient enrollment thereof and the expected timing for the release of data from those trials, including its planned Phase 2 KOURAGE trial of Auxora in AKI with associated AHRF, its ongoing Phase 2b trial of Auxora for AP with accompanying SIRS, its ongoing Phase 1/2 trial of Auxora in pediatric patients with AIPT, and its Phase 2 dose-ranging pharmacodynamic study in critical COVID-19 patients; the potential benefits of Auxora for the treatment of AKI, AP and AIPT; the potential of Auxora for the treatment of other acute indications including acute respiratory distress syndrome; the potential of CalciMedica's proprietary technology to provide therapeutic benefits in life-threatening inflammatory and immunologic diseases; pre-clinical and clinical studies of Auxora supporting the rationale for and design for the KOURAGE trial and the estimated patient population in the United States for AKI. These forward-looking statements are subject to the safe harbor provisions under the Private Securities Litigation Reform Act of 1995. CalciMedica's expectations and beliefs regarding these matters may not materialize. Actual outcomes and results may differ materially from those contemplated by these forward-looking statements as a result of uncertainties, risks, and changes in circumstances, including but not limited to risks and uncertainties related to: the impact of fluctuations in global financial markets on CalciMedica's business and the actions it may take in response thereto; CalciMedica's ability to execute its plans and strategies; the ability to obtain and maintain regulatory approval for Auxora; results from clinical trials or preclinical studies may not be indicative of results that may be observed in the future; potential safety and other complications from Auxora; the scope progress and expansion of developing and commercializing Auxora; the size and growth of the market therefor and the rate and degree of market acceptance thereof; economic, business, competitive, and/or regulatory factors affecting the business of CalciMedica generally; CalciMedica's ability to protect its intellectual property position; and the impact of government laws and regulations. Additional risks and uncertainties that could cause actual outcomes and results to differ materially from those contemplated by the forward-looking statements are included under the caption "Risk Factors" in CalciMedica's Quarterly Report on Form 10-Q for the quarter ended September 30, 2023 and elsewhere in CalciMedica's subsequent reports on Form 10-K, Form 10-Q or Form 8-K filed with the SEC from time to time and available at . These documents can be accessed on CalciMedica's web page at ir.calcimedica.com/financials-filings/sec-filings. CalciMedica Contact: Investors and Media Argot Partners Sarah Sutton/Kevin Murphy calcimedica@argotpartners.com (212) 600-1902 Company Codes: NASDAQ-NMS:CALC

Presented updated data from ongoing Phase 1 study of TSC-100 and TSC-101 for the treatment of heme malignancies at the Tandem Meetings of ASTCT and CIBMTR; 8/8 (100%) patients in treatment arms are relapse-free and show complete donor chimerism Announced the clearance of two additional INDs for Solid Tumor Program: TSC-201-B0702 targeting MAGE-C2 on HLA-B*07:02 and TSC-204-A0101 targeting MAGE-A1 on HLA-A*01:01 Solid tumor clinical trial actively enrolling, with initial data for singleplex and multiplex cohorts anticipated in 2024 Expands leadership team with key appointments and promotions Cash, cash equivalents, and marketable securities continues to fund operations into 2026 WALTHAM, Mass., March 06, 2024 (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 for the three months and full year ended December 31, 2023, and provided a business update. “The advancements we made across our pipeline in 2023 have set the stage for a momentous year ahead as we continue to treat and follow patients in the heme malignancies study and commence patient dosing in the solid tumor program. We continue to make meaningful progress with our Phase 1 heme malignancies study, with updated data on eight treatment-arm patients and six control-arm patients presented at the Tandem Meetings of ASTCT and CIBMTR,” said Gavin MacBeath, Ph.D., Chief Executive Officer. “We are encouraged to see that none of the patients in the treatment arms has relapsed following treatment with TSC-100 or TSC-101, including one high-risk TP53-mutated MDS patient who has now reached one year of follow-up. The one-year mark is a meaningful milestone for patients as the likelihood of relapse is now much lower, leading to an improved quality of life. We look forward to completing Phase 1 enrollment and reporting clinical and translational data in 2024 with two-year relapse-free survival data in 2025.” “We are on-track to treat the first patient in our Phase 1 solid tumor program this month, which will bring us one step closer to delivering customized, enhanced, multiplexed TCR-T therapies to patients with a variety of solid tumors,” said Debora Barton, M.D., Chief Medical Officer. “Solid tumors are notoriously heterogenous, with tumors frequently expressing more than one target antigen. We believe the only way to eradicate solid tumors is through a multi-targeted approach. To make this a reality, we continue to prioritize expanding the ImmunoBank with additional TCRs to increase patient eligibility for multiplexed therapy. With recent FDA clearance of our INDs for TSC-201-B0702 and TSC-204-A0101, we now have six TCR-Ts cleared for clinical development. We look forward to continuing to advance the solid tumor program and sharing data on patients from singleplex and multiplex cohorts in 2024.” Recent Corporate Highlights In February 2024, the Company presented updated Phase 1 clinical results on lead TCR-T candidates TSC-100 and TSC-101 at the Tandem Meetings: Transplantation & Cellular Therapy Meetings of the American Society for Transplantation and Cellular Therapy (ASTCT®) and the Center for International Blood and Marrow Transplant Research (CIBMTR®). Data showed that all eight (100%) treatment-arm patients were free from relapse, including four patients with follow-up beyond ten months. Notably, one high-risk TP53-mutated MDS patient has now reached the one-year mark following treatment with TSC-101. Additionally, no patient-derived hematopoietic cells were detected in any of the eight treatment-arm patients, indicating complete elimination of target cells. One AML patient with detectable disease post-transplant converted to, and continues to show, no detectable disease following treatment with TSC-101, with the most recent measurement at day 180. Patients have now been enrolled up to the third and final dose level in both treatment arms with no dose limiting toxicities thus far, suggesting that the third dose level will likely become the recommended Phase 2 dose.Of the six patients enrolled in the control arm (transplant alone), two control-arm patients relapsed at day 161 and day 180, and one of them succumbed to the relapse on day 265 post-transplant. A third control-arm patient required clinical intervention on day 133 because of concerns of impending relapse, and only two of the control-arm patients achieved and maintained complete donor chimerism following transplantation.The Company hosted a virtual KOL event following the Tandem Meetings to discuss these data. A replay of the event can be found here. The Company recently received U.S. Food and Drug Administration (FDA) clearance of its investigational new drug (IND) applications for two additional TCR-Ts in their Solid Tumor Program: TSC-201-B0702, a TCR-T targeting melanoma-associated antigen C2 (MAGE-C2) on HLA -B*07:02TSC-204-A0101, a TCR-T targeting melanoma-associated antigen 1 (MAGE-A1) on HLA-A*01:01 With the clearance of these IND applications, TScan now has six enhanced TCR-Ts cleared for clinical development. The Company remains on-track to dose the first patient in its Phase 1 solid tumor program in the first quarter of 2024 and anticipates sharing initial data on patients from both the singleplex and multiplex cohorts in 2024. The Company will present two “Trials in Progress” poster presentations at the upcoming American Association for Cancer Research (AACR) Annual Meeting 2024. Details for the posters include: Title: Trial in progress: A phase 1 trial of TSC-100 and TSC-101, engineered T cell therapies that target minor histocompatibility antigens to eliminate residual disease after hematopoietic cell transplantationSession Title: Phase I Clinical Trials in Progress 2Session Date and Time: Monday April 8, 2024; 1:30 - 5:00 PM PDTLocation: Poster Section 50Poster Board Number: 2Abstract Presentation Number: CT151 Title: Trial in progress: A phase 1, first in human clinical trial for T-Plex, a multiplexed, enhanced T cell receptor-engineered T cell therapy (TCR-T) for solid tumorsSession Title: Phase I Clinical Trials in Progress 2Session Date and Time: Monday April 8, 2024; 1:30 - 5:00 PM PDTLocation: Poster Section 50Poster Board Number: 21Abstract Presentation Number: CT170 The Company continues to expand its leadership team with key appointments and promotions: Appointed Jason A. Amello as Chief Financial OfficerAppointed Justin McCue, Ph.D., as Chief Technology OfficerPromoted Zoran Zdraveski, J.D., Ph.D., to Chief Legal and Strategy OfficerAppointed R. Keith Woods to its Board of DirectorsPromoted Cagan Gurer, Ph.D., to Senior Vice President, DiscoveryPromoted Jim Murray to Senior Vice President, Head of Development OperationsAppointed Dawn Pinchasik, M.D., M.S., as Vice President, Clinical Development In November 2023, the Company was named a Top Place to Work by The Boston Globe for the second consecutive year. Upcoming Anticipated Milestones Heme Malignancies Program: TScan’s two lead TCR-T cell therapy candidates, TSC-100 and TSC-101, are designed to treat residual disease and prevent relapse in patients with acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), or myelodysplastic syndromes (MDS) undergoing hematopoietic cell transplantation (HCT) (NCT05473910). Plans to open expansion cohorts at the recommended Phase 2 dose level to further characterize safety and evaluate translational and efficacy endpoints in the third quarter of 2024.Plans to complete Phase 1 enrollment and report one-year clinical and translational data on initial patients in 2024.Expects to initiate registration trial and report two-year relapse data in 2025. Solid Tumor Program: TScan continues to expand the ImmunoBank, a collection of therapeutic TCRs that target different cancer-associated antigens presented on diverse HLA types. TScan’s strategy is to treat patients with multiple TCR-Ts to overcome tumor heterogeneity and prevent resistance that may arise from either target or HLA loss (screening protocol: NCT05812027) (treatment protocol: NCT05973487). Initiated Phase 1 solid tumor clinical study and expects to dose the first patient in the first quarter of 2024.Expects to share initial data on patients from both singleplex and multiplex cohorts in 2024.Plans to continue to expand the ImmunoBank with additional IND filings throughout 2024.Long-term duration of response data for multiplexed therapy anticipated in 2025. Financial Results Revenue: Revenue for the fourth quarter of 2023, was $7.2 million, compared to $3.1 million for the fourth quarter of 2022, and $21.0 million for the full-year 2023, compared to $13.5 million for the full-year 2022. The increase in both periods is primarily due to timing of research activities related to the collaboration agreement with Amgen which commenced in May 2023 compared to the collaboration and license agreement with Novartis which ended in March 2023. R&D Expenses: Research and development expenses for the fourth quarter of 2023 were $22.4 million, compared to $15.6 million for the fourth quarter of 2022, and $88.2 million for the full-year 2023, compared to $59.8 million for the full-year 2022. The period over period increases were primarily driven by increased costs associated with clinical trial start-up fees and patient enrollment, increased personnel costs, and expansion of facilities. G&A Expenses: General and administrative expenses for the fourth quarter of 2023, were $6.2 million, compared to $6.1 million for the fourth quarter of 2022, and $26.4 million for the full-year 2023, compared to $20.4 million for the full-year 2022. The full-year increase of $6.0 million was primarily driven by increased legal and professional fees and expansion of facilities. Net Loss: Net loss was $19.6 million for the fourth quarter of 2023, compared to $18.7 million for the fourth quarter of 2022, and included net interest income of $1.7 million and $0, respectively. Net loss for the full-year 2023 was $89.2 million, compared to $66.2 million for the full-year 2022, and included net interest income of $4.2 million and $0.4 million, respectively. Cash Position: Cash, cash equivalents, and marketable securities as of December 31, 2023 were $192.0 million, excluding $5.0 million of restricted cash. The Company believes that its existing cash resources will be sufficient to fund its current operating plan into 2026. Share Count: As of December 31, 2023, the Company had issued and outstanding shares of 47,829,529, which consists of 43,552,941 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 prevent relapse following allogeneic hematopoietic cell transplantation. The Company is also developing TCR-T therapy candidates for the treatment of various solid tumors. The Company has developed and continues to expand 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 cancers. 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 potential indicators of treatment success, completion of enrollment and opening of expansion cohorts, and the presentation of data; the Company’s plans, progress, and timing relating to the Company’s solid tumor programs, including treatment of patients and the presentation of data; 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 ability to fund its operating expenses and capital expenditure requirements with its existing cash and cash equivalents; and the Company’s goals and strategy, focus, and anticipated financial performance. 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; TScan’s recently approved INDs being indicative or predictive of bringing TScan closer to its goal of providing customized TCR-T therapies to treat patients with cancer; the timing of the launch, initiation, progress, 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 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(in thousands) December 31,2023 December 31, 2022 Assets Cash, cash equivalents, and marketable securities$192,044 $120,027 Other assets 80,105 79,064 Total assets$272,149 $199,091 Liabilities and Stockholders' Equity Total liabilities$121,282 $99,657 Total stockholders' equity 150,867 99,434 Total liabilities and stockholders' deficit$272,149 $199,091 TScan Therapeutics, Inc.Condensed Consolidated Statements of Operations(in thousands, except share and per share amounts) Three Months Ended December 31, Twelve Months Ended December 31, 2023 2022 2023 2022 Revenue: Collaboration and license revenue$7,211 $3,096 $21,049 $13,535 Operating expenses: Research and development 22,407 15,604 88,153 59,819 General and administrative 6,161 6,140 26,354 20,352 Total operating expenses 28,568 21,744 114,507 80,171 Loss from operations (21,357) (18,648) (93,458) (66,636)Other income 2,596 900 7,999 1,591 Interest expense (852) (975) (3,759) (1,176)Net loss$(19,613) $(18,723) $(89,218) $(66,221)Net loss per share, basic and diluted$(0.21) $(0.78) $(1.36) $(2.75)Weighted average common shares outstanding—basic and diluted 94,835,735 24,077,857 65,599,858 24,048,267