Pre B-cell 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.

All eight (100%) treatment-arm patients are relapse-free and have achieved and maintained complete donor chimerism following treatment with TSC-100 or TSC-101 Patient with high-risk, TP53-mutated MDS is relapse-free for over one year following treatment with TSC-101 Patient with AML converted from detectable to undetectable disease following treatment with TSC-101 Data presented at TANDEM meeting suggests complete donor chimerism is an early indicator of treatment success Company to host virtual KOL event today, Monday, February 26, at 8:00 a.m. ET, to discuss the data presented at the 2024 Tandem Meetings WALTHAM, Mass., Feb. 26, 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 announced an oral presentation at the 2024 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®). The oral presentation, selected for the plenary session as a Best Abstract, highlights updated data from the Phase 1 multi-arm clinical trial evaluating TSC-100 and TSC-101, designed to treat residual disease and prevent relapse following hematopoietic cell transplantation (HCT) in patients with acute myeloid leukemia (AML), myelodysplastic syndromes (MDS), or acute lymphocytic leukemia (ALL) (NCT05473910). “We are excited to report updated data from our heme program, with eight patients across our treatment arms and six patients in our control arm. We remain encouraged to see that no relapses have occurred to date in treated patients, four of whom have been on the study for over ten months. One patient with high-risk, TP53-mutated MDS has now reached the one-year mark following treatment with TSC-101, a meaningful milestone as the likelihood of relapse decreases significantly over time, leading to an improved quality of life,” said Debora Barton, M.D., Chief Medical Officer. “We have also enrolled six patients in the control arm, receiving transplant alone. To date, two control-arm patients relapsed following transplant, at days 161 and 180, and one of these patients succumbed to the relapse at day 265. A third patient required clinical intervention at day 133 because of concerns of impending relapse.” “Sustained complete donor chimerism may be the most valuable indicator of treatment success,” added Gavin MacBeath, Ph.D., Chief Executive Officer. “HCT is currently the best treatment option for many patients suffering from AML, MDS, and ALL, as approximately 60% of patients are cured by this treatment. Unfortunately, roughly 40% of patients relapse following HCT, at which point there are limited treatment options and a poor prognosis. Donor chimerism measures any remaining patient-derived hematopoietic cells that could potentially lead to relapse. We are using a high-sensitivity next-generation sequencing assay to track donor chimerism in all patients in our study. We are encouraged to see that all eight patients treated with our cell therapy products achieved and maintained complete donor chimerism at every time-point, with four of these patients past the 10-month mark. This is a very good sign for these patients, and we look forward to sharing follow-up data, as well as data on additional patients, as the study continues to enroll in 2024.” The Phase 1 trial is a multi-arm dose escalation study evaluating TSC-100 and TSC-101, which are designed to treat residual disease and prevent relapse following HCT in patients with AML, ALL or MDS undergoing haploidentical donor allogeneic HCT with reduced intensity conditioning. Primary endpoints include safety and dose-finding, and secondary and exploratory endpoints include relapse rates versus standard-of-care (HCT alone) as well as supportive surrogates of efficacy, including donor chimerism and minimal residual disease (MRD). MRD identifies any residual disease-related DNA present in a patient, and chimerism measures any remaining recipient-derived hematopoietic cells in a patient following HCT (NCT05473910). Key Presentation Highlights Include: TSC-100 treatment arm (N=4: T-ALL, AML, AML, MDS) 4/4 patients treated with TSC-100 achieved complete donor chimerism with no relapse. TSC-101 treatment arm (N=4: TP53-mutated MDS, AML, B-ALL, B-ALL) 4/4 patients treated with TSC-101 achieved complete donor chimerism with no relapse, including a patient with high-risk, TP53-mutated MDS who has reached one year of follow-up.One patient with AML was MRD-positive following HCT and converted to and maintained MRD-negative status following treatment with TSC-101 (most recent measurement at day 180). TSC-100 and TSC-101 persistence noted for prolonged periods: Persistence of TSC-100 and TSC-101 was observed at all time points after dosing, with the longest follow-up of over 9 months.Repeat dosing (dose levels 2 and 3) led to a 3-fold increase in circulating TSC-100 and TSC-101 levels compared to single dosing (dose level 1) at the same time points. Six control arm patients (MDS, MDS, MDS, AML, AML, AML) have been enrolled and received standard of care HCT alone: One control-arm patient with high-risk, TP53-mutated MDS evolved with MRD positivity and worsening mixed chimerism, experienced clinical relapse approximately six months post-transplant, and succumbed to relapse approximately nine months post-transplant.One control-arm patient with MDS experienced clinical relapse approximately five months post-transplant.One control-arm patient with MDS developed worsening mixed chimerism requiring early termination of immunosuppression, resulting in complete donor chimerism but with grade 1 skin graft-versus-host disease.One control-arm patient never achieved complete donor chimerism, with more than four months follow-up post-transplant.2/6 control-arm patients achieved complete donor chimerism following HCT. Virtual KOL Event The Company will host a virtual KOL event featuring: Monzr M. Al Malki, M.D., 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 HopeRan Reshef, M.D., M.Sc., Professor of Medicine and Director of the Cellular Immunotherapy Program at Columbia University Irving Medical Center The conference call will be held today, February 26, at 8:00 a.m. ET, to discuss the data presented at the Tandem Meetings. Details for attending the live event can be found here. A replay will be made available on the “Events and Presentations” section of the Company’s investor relations 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 expand its ImmunoBank, the Company’s repository of therapeutic TCRs that recognize diverse targets and are associated with multiple HLA types, to provide customized, enhanced, 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 the potential implications of initial data from a large prospective clinical trial, presentation of additional data, and potential indicators of treatment success; the potential benefits of any of the Company’s current or future product candidates in treating patients; 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. ContactsHeather SavelleTScan Therapeutics, Inc.VP, Investor Relations857-399-9840hsavelle@tscan.com Joyce AllaireLifeSci Advisors, LLCManaging Director617-435-6602jallaire@lifesciadvisors.com

Iomab-B significantly improved outcomes in TP53 positive patients with a median overall survival of 5.49 months versus 1.66 months in those not receiving Iomab-B (hazard ratio = 0.23, p-value=0.0002) in the Phase 3 SIERRA Trial The results demonstrate Iomab-B's ability to overcome the negative impact of a TP53 mutation in these patients who otherwise would have limited treatment options and dismal prognosis Five presentations include two upcoming oral presentations detailing improved outcomes in SIERRA trial patients ages 65+ and demonstration of robust engraftment with Iomab-B NEW YORK, Feb. 23, 2024 /PRNewswire/ -- Actinium Pharmaceuticals, Inc. (NYSE AMERICAN: ATNM) (Actinium or the Company), a leader in the development of targeted radiotherapies, today highlighted results from three poster presentations at the 2024 Tandem Meetings | Transplantation & Cellular Therapy (TCT) Meetings of ASTCT® (American Society for Transplantation and Cellular Therapy and CIBMTR® (Center for International Blood and Marrow Transplant Research) being held in San Antonio, Texas. The posters detailed results and findings from the Phase 3 SIERRA trial of Iomab-B (131I-Apamistamab) including; improved rates of Complete Remission (CR), durable Complete Remission (dCR) and survival in patients with a TP53 mutation, key aspects of radiopharmaceutical dosimetry as related to Iomab-B, and early results from a Phase 1 study demonstrating safety and lymphodepletion from Iomab-ACT conditioning with CD19 CAR-T therapy. Dr. Avinash Desai, Actinium's Chief Medical Officer, said, "Patients with a TP53 mutation have a desperate need for viable treatment options to improve outcomes. As seen in the SIERRA trial, Iomab-B led bone marrow transplant can overcome the negative impact of a TP53 mutation, producing complete remissions in more than 50% of patients as well as significant durable complete remissions. This is in stark contrast to the 0% complete remission and durable complete remission rate seen in the TP53 positive patients on the control arm who received best available treatment based on physician's choice. We are excited to further highlight these important outcomes to the transplant community and look forward to presenting additional findings from the SIERRA trial in our upcoming oral presentations." The presented Iomab-B Phase 3 SIERRA trial results and highlights include: Response Rate by TP53 Mutational Status and Treatment CR = Complete Remission Improved Survival with Iomab-B Upcoming Iomab-B Phase 3 SIERRA Trial 2024 TCT Oral Presentations: Title: 131I-Apamistamab Improves Outcomes in Patients 65 Years and Older with Relapsed or Refractory AML Date & Time: Saturday, February 24, 2024, at 11:45 AM Title: Targeted Myeloablative Radiation Using 131I-Apamistamab Prior to Allogeneic Hematopoietic Cell Transplant for Patients with R/R AML Results in Robust Engraftment Date & Time: Saturday, February 24, 2024, at 10:30 AM In addition, Actinium presented results from its ongoing phase 1 trial using Iomab-ACT as conditioning prior to CD19 CAR-T therapy for patients with relapsed or refractory B-cell Acute Lymphoblastic Leukemia or Diffuse Large B-cell Lymphoma. Importantly, no patients (0/4) developed immune effector cell-associated neurotoxicity syndrome (ICANS) of any grade, a major safety measure of the study, as ICANS is observed in 25% or more of pts w/ R/R B-ALL and DLBCL treated with various CAR T-cell products. Iomab-ACT demonstrated transient depletion of peripheral blood lymphocytes and monocytes. Persistence of CAR T-cells up to 8 weeks and minimal non-hematologic toxicities have been observed to date. About the TCT Tandem Meetings The Tandem Meetings I Transplantation & Cellular Therapy Meetings of ASTCT and CIBMTR are the combined annual meetings of the American Society for Transplantation and Cellular Therapy (ASTCT) and the Center for International Blood & Marrow Transplant Research (CIBMTR). Administrators, clinicians, data manager / clinical research professionals, fellows-in-training, investigators, laboratory technicians, MD/PhDs, nurses, nurse practitioners, pharmacists, physician assistants, and other allied health professional attendees benefit from a full scientific program that addresses the most timely issues in hematopoietic cell transplantation and cellular therapy. About Actinium Pharmaceuticals, Inc. Actinium develops targeted radiotherapies to meaningfully improve survival for people who have failed existing oncology therapies. Advanced pipeline candidates Iomab-B (pre-BLA & MAA (EU)), an induction and conditioning agent prior to bone marrow transplant, and Actimab-A (National Cancer Institute CRADA pivotal development path), a therapeutic agent, have demonstrated potential to extend survival outcomes for people with relapsed and refractory acute myeloid leukemia. Actinium plans to advance Iomab-B for other blood cancers and next generation conditioning candidate Iomab-ACT to improve cell and gene therapy outcomes. Actinium holds more than 220 patents and patent applications including several patents related to the manufacture of the isotope Ac-225 in a cyclotron. For more information, please visit: Forward-Looking Statements This press release may contain projections or other "forward-looking statements" within the meaning of the "safe-harbor" provisions of the private securities litigation reform act of 1995 regarding future events or the future financial performance of the Company which the Company undertakes no obligation to update. These statements are based on management's current expectations and are subject to risks and uncertainties that may cause actual results to differ materially from the anticipated or estimated future results, including the risks and uncertainties associated with preliminary study results varying from final results, estimates of potential markets for drugs under development, clinical trials, actions by the FDA and other governmental agencies, regulatory clearances, responses to regulatory matters, the market demand for and acceptance of Actinium's products and services, performance of clinical research organizations and other risks detailed from time to time in Actinium's filings with the Securities and Exchange Commission (the "SEC"), including without limitation its most recent annual report on form 10-K, subsequent quarterly reports on Forms 10-Q and Forms 8-K, each as amended and supplemented from time to time. Investors: [email protected] SOURCE Actinium Pharmaceuticals, Inc.