Thymoma

CELLphenomics’ PD3D® tumor model platform will expand Charles River’s portfolio of 3D in vitro testing services WILMINGTON, Mass. & BERLIN--(BUSINESS WIRE)-- Charles River Laboratories Laboratories International, Inc. (NYSE: CRL) today announced that it has entered into an agreement with CELLphenomics, a service-based biotechnology company that is using 3D hydrogel technology to advance the understanding of the tumor microenvironment and predict therapeutic efficacy. This enhanced offering will provide Charles River clients with access to CELLphenomics’ proprietary 3D tumor model platform, PD3D®, expanding Charles River’s 3D in vitro testing services to further optimize oncological approaches for its clients. CELLphenomics’ core competency is the establishment and cultivation of complex patient-derived 3D cell culture models (PD3D) from various solid tumor tissues. These highly reliable, well-annotated and predictive preclinical PD3D models robustly recapitulate the biological properties of the donor tissue, including key histopathological features and genomic makeup. They are a powerful tool for disease modeling, biomarker and drug discovery. CELLphenomics’ continuously growing biobank comprises more than 500 complex in vitro models from more than 20 tumor entities, and offers the world’s largest collection of complex in vitro models of rare and ultra-rare tumors like sarcomas or thymomas. CELLphenomics has developed a custom mid-throughput screening platform that blends complex cell culture models with advanced automation and a streamlined analysis pipeline. The proprietary, precision medicine PD3D platform offers mid-throughput efficacy testing, drug combination screening, toxicity profiling, target validation, drug sensitivity correlation with clinical response, and biomarker identification. Charles River offers a range of cancer cell-based assays, including patient-derived xenograft (PDX) assays and assays representing the entire tumor microenvironment (TME), so therapies are not only tested for their effect on real patient materials, but also their interaction with the human immune systems. Leveraging CELLphenomics technology, Charles River will now have a novel in vitro option for identifying therapeutics for rare and ultra-rare disease types. The agreement will also provide CELLphenomics access to Charles River’s genomically annotated and in vivo characterized cancer model database to develop PD3D models. The database is comprised of more than 700 tumor models, including PDX, cell lines and cell line-derived xenografts (CDX). These models have been extensively profiled for histological features, molecular data, and sensitivity to standard-of-care compounds, allowing a precise selection of suitable tumor models for preclinical anti-cancer agent testing. The biological advantages of PDX include the retention of histological and genetic characteristics of the donor tumor and the preservation of cell-autonomous heterogeneity. The merge of both biobanks will significantly increase the translational relevance of the in vitro and in vivo platforms offered by CELLphenomics and Charles River. Approved Quotes “The field of 3D in vitro services for oncology research is rapidly developing. We’re excited for the integration of CELLphenomics’ tumor model platform into our existing portfolio of products and services.” – Aidan Synnott, Corporate Vice President, Global Discovery Services, Charles River “Our clients will benefit from this enhanced offering, but ultimately, our work will benefit patients who desperately need new treatments for cancer.” –Julia Schueler, PhD, Research Director and Therapeutic Area Lead, Oncology, Charles River “This agreement allows us full access to Charles River’s impressive biobank and data. Now we can provide them with high quality models of the same genomic background through the entire preclinical development process – literally for any solid tumor type. From large high-throughput in vitro screens to selected PDX models, with Charles River as our partner, we can ensure an even more swiftly developmental process for novel anti-cancer drugs. Together, we make our customers’ compounds work.” –Dr. Christian Regenbrecht, CEO, CELLphenomics About Charles River Charles River provides essential products and services to help pharmaceutical and biotechnology companies, government agencies and leading academic institutions around the globe accelerate their research and drug development efforts. Our dedicated employees are focused on providing clients with exactly what they need to improve and expedite the discovery, early-stage development and safe manufacture of new therapies for the patients who need them. To learn more about our unique portfolio and breadth of services, visit . About CELLphenomics CELLphenomics establishes and cultivates complex patient-derived 3D cell culture models (PD3D®) from various solid tumor tissues. The company’s in vitro services combine wet-lab biology, automation and high throughput screening directly on patient samples to help predict responses to potential therapies, and ultimately determine which drugs or drug combinations will be most effective for specific types of cancers, visit:

Results are encouraging regarding the benefit of immunotherapy across racial and ethnic groups, but also reinforce need to include more Black and Hispanic people in cancer clinical trials and highlight the importance of equitable treatment delivery for closing disparities in outcomes. PLYMOUTH MEETING, Pa., Dec. 11, 2023 /PRNewswire/ -- New research in the December 2023 issue of JNCCN—Journal of the National Comprehensive Cancer Network finds patients treated with first-line immunotherapy for advanced Non-Small Cell Lung Cancer (NSCLC) showed similar results in terms of survival, progression-free survival, and treatment duration, regardless of race or ethnicity, even with differences in income and insurance. The clinical investigators focused on patients in under-represented groups who were typically less likely to be included in the immunotherapy clinical trials that have been conducted to date. They analyzed results from 248 patients treated with pembrolizumab over a 9-year period between January 1, 2013 and June 1, 2022, with non-Hispanic Black, Hispanic, and Non-Hispanic White patients each accounting for an approximately equal percentage. Median overall survival was 16.8 to 26.3 months, similar to results previously reported in large prospective clinical trials. Continue Reading This study could change how we take care of patients and plan future lung cancer studies to better include all patients. Post this December 2023 Edition of JNCCN now available at JNCCN.org. "There has not been enough information on how immunotherapy affected racially- and ethnically-marginalized patients with lung cancer in the past, because they were not well-represented in most previous studies," explained lead investigator Matthew Lee, MD, MPH, Assistant Professor of Oncology, Montefiore Einstein Comprehensive Cancer Center (MECCC). "The findings from this study could change how we take care of patients and plan future lung cancer studies to better include all patients. While immunotherapy has significantly improved survival for lung cancer patients overall, differences exist in its administration among individuals of different races and ethnicities. This finding could potentially promote the use of immunotherapy in more diverse patient populations." The study results included other notable findings. While race, ethnicity, income, and insurance status did not statistically impact survival, the investigators were surprised to find that higher BMI was associated with longer progression-free survival and shorter time to treatment discontinuation. They also determined that a worse ECOG Performance Status—a standardized tool for measuring how capably a patient can take care of themself, do regular activities, or move around—was significantly more likely to result in poorer outcomes. "This study highlights the potential importance of adjusting treatment approaches in clinical practice, particularly for patients with a poor ECOG performance status," said senior researcher Haiying Cheng, MD, PhD, Associate Professor of Oncology and Member of the MECCC Cancer Therapeutics Research Program. "There is a clear need for future studies to include underrepresented patient groups in clinical trials to validate these findings and to better guide clinical practice." "This retrospective study provides valuable real-world information on the clinical outcomes of patients from underrepresented racial/ethnic groups undergoing immunotherapy for metastatic NSCLC," commented Debora S. Bruno MD, MS, Assistant Professor of Medicine - Case Western Reserve University; Medical Director, Dahms Clinical Research Unit, University Hospitals - Cleveland Medical Center, Seidman Cancer Center at Case Comprehensive Cancer Center, who was not involved in this research. "Non-Hispanic Black and Hispanic individuals were gravely underrepresented in registrational immunotherapy trials for lung cancer. As a result, there is a paucity of prospective trial data on the efficacy and safety of this class of antineoplastic agents for such patients." Dr. Bruno, a Member of the NCCN Guidelines® Panel for Non-Small Cell Lung Cancer/Mesothelioma/Thymomas and Thymic Carcinomas, continued: "While it is certainly reassuring to see a lack of real world racial and ethnic disparities in clinical outcomes when patients receive adequate therapy for their disease, we must continue and strive for equitable representation for all patients in prospective oncology clinical trials." To read the entire study, visit JNCCN.org. Complimentary access to "Similar Efficacy Observed for First-Line Immunotherapy in Ethnic Minority Patients With Metastatic NSCLC" is available until March 10, 2024. About JNCCN—Journal of the National Comprehensive Cancer Network More than 25,000 oncologists and other cancer care professionals across the United States read JNCCN—Journal of the National Comprehensive Cancer Network. This peer-reviewed, indexed medical journal provides the latest information about innovation in translational medicine, and scientific studies related to oncology health services research, including quality care and value, bioethics, comparative and cost effectiveness, public policy, and interventional research on supportive care and survivorship. JNCCN features updates on the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®), review articles elaborating on guidelines recommendations, health services research, and case reports highlighting molecular insights in patient care. JNCCN is published by Harborside/BroadcastMed. Visit JNCCN.org. To inquire if you are eligible for a FREE subscription to JNCCN, visit NCCN.org/jnccn/subscribe. Follow JNCCN on Twitter @JNCCN. About the National Comprehensive Cancer Network The National Comprehensive Cancer Network® ( NCCN ®) is a not-for-profit alliance of leading cancer centers devoted to patient care, research, and education. NCCN is dedicated to improving and facilitating quality, effective, equitable, and accessible cancer care so all patients can live better lives. The NCCN Clinical Practice Guidelines in Oncology ( NCCN Guidelines ®) provide transparent, evidence-based, expert consensus recommendations for cancer treatment, prevention, and supportive services; they are the recognized standard for clinical direction and policy in cancer management and the most thorough and frequently-updated clinical practice guidelines available in any area of medicine. The NCCN Guidelines for Patients® provide expert cancer treatment information to inform and empower patients and caregivers, through support from the NCCN Foundation®. NCCN also advances continuing education, global initiatives, policy, and research collaboration and publication in oncology. Visit NCCN.org for more information. Media Contact: Rachel Darwin 267-622-6624 [email protected] SOURCE National Comprehensive Cancer Network

– First cleared CD19-CAR T IND application for generalized myasthenia gravis announced in the U.S. and fourth IND clearance for CABA-201 across a broad range of autoimmune diseases – – Clearance expands the clinical development of CABA-201 beyond rheumatology into neurology – – Phase 1/2 clinical trial evaluating CABA-201 in generalized myasthenia gravis features parallel cohort design and a starting dose consistent with the previously announced Phase 1/2 trials of CABA-201 for lupus, myositis and systemic sclerosis – PHILADELPHIA, Nov. 06, 2023 (GLOBE NEWSWIRE) -- Cabaletta Bio, Inc. (Nasdaq: CABA), a clinical-stage biotechnology company focused on developing and launching the first curative targeted cell therapies for patients with autoimmune diseases, today announced that the Company’s fourth Investigational New Drug (IND) application for CABA-201, a 4-1BB-containing fully human CD19-CAR T cell investigational therapy, has been allowed to proceed by the U.S. Food and Drug Administration (FDA) for a Phase 1/2 study in patients with generalized myasthenia gravis (gMG). The Company plans to initiate a Phase 1/2 clinical trial of CABA-201 across two parallel gMG cohorts based on autoantibody status – one cohort of six patients with acetylcholine receptor (AChR) antibody-positive gMG and a second cohort of six patients with AChR antibody-negative gMG. Consistent with the previously announced CABA-201 IND application clearances for lupus, myositis and systemic sclerosis, the starting dose for the Phase 1/2 trial evaluating CABA-201 in gMG will be 1 x 106 cells/kg. “While we remain on track to deliver initial clinical data from CABA-201 treated patients with lupus and/or myositis in the first half of 2024, we are continuing to expand our CABA-201 portfolio beyond rheumatology and into neurology. The announcement of our fourth CABA-201 IND clearance is also our first IND clearance for the product candidate in a predominantly autoantibody mediated disease. Consistent with previously announced CABA-201 trials, the Phase 1/2 clinical trial design for CABA-201 in gMG includes the same starting dose as used in the previously cleared clinical trials with CABA-201 and parallel cohorts of six patients. While prioritizing delivery of initial clinical data in the first half of 2024 from our myositis and/or lupus trials, our clinical operations team is well positioned to execute the gMG program based on experience with MG sites in our legacy CAART platform,” said Steven Nichtberger, M.D., Chief Executive Officer and Co-founder of Cabaletta. “Despite recent advances with chronic, broadly immunosuppressive therapies, we believe there is an unmet need for a treatment option like CABA-201 that may provide a deep and durable, perhaps curative, outcome with a single dose in patients with gMG.” Myasthenia gravis (MG) is a rare autoimmune disease characterized by autoantibodies that interfere with signaling at the neuromuscular junction (NMJ), leading to potentially life-threatening muscle weakness. The majority of patients with MG have autoantibodies known to be pathogenic based on their interference with proteins in the NMJ, of which the majority target AChR. Generalized MG affects approximately 85% of the between 50,000 and 80,000 estimated MG patients in the United States. Symptoms of gMG include profound muscle weakness throughout the body, disabling fatigue, shortness of breath due to respiratory muscle weakness and risk for episodes of respiratory failure. Standard of care therapies include cholinesterase inhibitors, steroids, immunomodulators, and biologics, which often provide modest clinical effect and require chronic administration, increasing the risk of serious long-term side effects. About the Phase 1/2 Clinical Trial of CABA-201 in gMGThe Phase 1/2 clinical trial will be an open-label study of CABA-201 in subjects with gMG across two parallel cohorts. The first cohort will include six patients with AChR antibody-positive gMG, and the second will include six patients with AChR antibody-negative gMG. Participants will receive a one-time infusion of CABA-201, using the same dose being used in the lupus, myositis and systemic sclerosis clinical trials of CABA-201, 1 x 106 cells/kg, preceded by a standard preconditioning regimen of fludarabine and cyclophosphamide. Key inclusion criteria include patients between ages 18 and 70 (inclusive), a diagnosis of gMG, and disease activity despite standard of care therapies. Key exclusion criteria include myasthenia gravis with only ocular manifestations, an active or untreated thymoma, and treatment with a B cell depleting agent within six months. As the fourth trial within Cabaletta’s CARTA (Chimeric Antigen Receptor T cells for Autoimmunity) strategy, this study is intended to evaluate the potential ability of CABA-201 to transiently, but completely, eliminate B cells throughout the body. About Cabaletta BioCabaletta Bio (Nasdaq: CABA) is a clinical-stage biotechnology company focused on the discovery and development of engineered T cell therapies that have the potential to provide a deep and durable, perhaps curative, treatment for patients with autoimmune diseases. The CABA™ platform encompasses two strategies: the CARTA (chimeric antigen receptor T cells for autoimmunity) strategy, with CABA-201, a 4-1BB-containing fully human CD19-CAR T, as the lead product candidate being evaluated in systemic lupus erythematosus, myositis, systemic sclerosis and generalized myasthenia gravis, and the CAART (chimeric autoantibody receptor T cells) strategy, with multiple clinical-stage candidates, including DSG3-CAART for mucosal pemphigus vulgaris and MuSK-CAART for MuSK myasthenia gravis. The expanding CABA™ platform is designed to develop potentially curative therapies that offer deep and durable responses for patients with a broad range of autoimmune diseases. Cabaletta Bio’s headquarters and labs are located in Philadelphia, PA. Forward-Looking StatementsThis press release contains “forward-looking statements” of Cabaletta Bio within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including without limitation, express or implied statements regarding its expectations regarding: Cabaletta’s ability to grow its autoimmune-focused pipeline; the ability to capitalize on and potential benefits resulting from published third-party academic clinical data; the anticipated market opportunities for CABA-201 in gMG patients; the Company’s business plans and objectives; Cabaletta’s expectations around the potential success and therapeutic benefits of CABA-201, including its belief in the potential for CABA-201 to provide a deep and durable, perhaps curative, outcome with a single dose in patients with gMG; the Cabaletta clinical operations team’s ability to execute the gMG program based on experience with MG sites in the Company’s legacy CAART platform; the Company’s plans to initiate and progress separate Phase 1/2 clinical trials of CABA-201 in subjects with gMG, SSc, SLE and myositis; the Company’s planned initial clinical data read-out from the CABA-201 program in the first half of 2024; and Cabaletta’s ability to enroll the requisite number of patients and dose each dosing cohort in the intended manner in its Phase 1/2 clinical trials of CABA-201. Any forward-looking statements in this press release are based on management’s current expectations and beliefs of future events, and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. These risks and uncertainties include, but are not limited to: risks related to regulatory filings and potential clearance; the risk that signs of biologic activity or persistence may not inform long-term results; Cabaletta’s ability to demonstrate sufficient evidence of safety, efficacy and tolerability in its preclinical studies and clinical trials of DSG3-CAART, MuSK-CAART and CABA-201; the risk that the results observed with the similarly-designed construct employed in the recent academic publications, including due to the dosing regimen, are not indicative of the results we seek to achieve with CABA-201; risks related to clinical trial site activation or enrollment rates that are lower than expected; risks related to unexpected safety or efficacy data observed during clinical studies; risks related to volatile market and economic conditions and public health crises; Cabaletta’s ability to retain and recognize the intended incentives conferred by Orphan Drug Designation and Fast Track Designation for its product candidates, as applicable; risks related to Cabaletta’s ability to protect and maintain its intellectual property position; risks related to fostering and maintaining successful relationships with Cabaletta’s collaboration and manufacturing partners; uncertainties related to the initiation and conduct of studies and other development requirements for its product candidates; the risk that any one or more of Cabaletta’s product candidates will not be successfully developed and/or commercialized; and the risk that the initial or interim results of preclinical studies or clinical studies will not be predictive of future results in connection with future studies. For a discussion of these and other risks and uncertainties, and other important factors, any of which could cause Cabaletta’s actual results to differ from those contained in the forward-looking statements, see the section entitled “Risk Factors” in Cabaletta’s most recent annual report on Form 10-K as well as discussions of potential risks, uncertainties, and other important factors in Cabaletta’s other and subsequent filings with the Securities and Exchange Commission. All information in this press release is as of the date of the release, and Cabaletta undertakes no duty to update this information unless required by law. Contacts: Anup MardaChief Financial Officerinvestors@cabalettabio.com William GramigStern Investor Relations, Inc.william.gramig@sternir.com