HLA-A

CDR-Life Inc. today announced a milestone payment triggered by the achievement of a development milestone with a partnered antibody fragment-based drug candidate that could significantly slow down the progression of geographic atrophy (GA). Boehringer Ingelheim and CDR-Life entered a collaboration and licensing agreement in May 2020 and announced the selection of an antibody fragment-based therapeutic candidate in September 2021. GA is a progressive, irreversible retinal disease and one of the leading causes of blindness in people over 65 years of age. It occurs in people living with age-related macular degeneration (AMD) and affects approximately eight million people globally. “This milestone is continued validation of the expertise of our team to identify high quality antibody fragment-based drug candidates across a broad range of therapeutic applications,” said Christian Leisner, Ph.D., Chief Executive Officer at CDR-Life. “Our partnership with Boehringer Ingelheim has proven successful and will hopefully bring life-changing new treatments for people living with this devastating disease.” In addition to partnering with Boehringer Ingelheim, CDR-Life is building its own pipeline of novel antibody fragment-based T cell engagers against solid tumors. By uniquely targeting the major histocompatibility complex (MHC), CDR-Life is able to access a new class of intracellular tumor antigens to engage T cells. The company’s first of several therapeutic candidates in development, CDR404, targets MAGE-A4 and is anticipated to enter the clinic in 2024. About CDR-Life CDR-Life is developing highly specific antibody therapeutics to target intracellular proteins presented on the major histocompatibility complex (MHC). Our versatile MHC-targeted antibody platform increases access to a vast array of antigens that were not previously addressable, to develop a pipeline of first in class therapeutics across a broad range of solid tumors. With a team of proven drug development experts and backed by leading cross-Atlantic investors, we are working to redirect and activate the patient’s own immune system to eliminate their tumors. The content above comes from the network. if any infringement, please contact us to modify.

--The molecules open the door for development of immunotherapies that are truly universal and work across HLA types, regardless of patient ancestry— PHILADELPHIA, June 13, 2023 /PRNewswire/ -- Class I major histocompatibility complex (MHC-I) proteins play an essential role in the immune system of all jawed vertebrates. The MHC-I displays peptide fragments of proteins from within the cell on the cell surface, "presenting" them to the immune system, which is constantly scanning the body for foreign or toxic antigens. When foreign peptides are identified, they trigger a cascade that allows cytotoxic T cells to eliminate intruders. This process has been exploited in the development of both vaccines and immunotherapy, wherein researchers identify fragments of peptides unique to viruses or cancer and then screen for T cells that recognize those targets and initiate an immune response. However, the current process of using MHC-I molecules as probes in vaccine and immunotherapy development is laborious. MHC-I molecules are extremely unstable, and making just one of these molecules can take a week, making it prohibitive to scan large libraries of peptides in an efficient manner. Now, researchers from Children's Hospital of Philadelphia (CHOP) have potentially solved this problem by engineering stable, universal MHC-I molecules that can be produced rapidly at scale, allowing researchers not only to develop vaccines and immunotherapies more quickly but also to identify molecules that can work broadly across the population. The findings were published today in the Proceedings of the National Academy of Sciences. "The findings in this paper have the potential to revolutionize this field, both in the way we manufacture these molecules and the rate at which we can screen for effective and universal immunotherapies," said senior author Nikolaos G. Sgourakis, PhD, Associate Professor in the Center for Computational and Genomic Medicine at Children's Hospital of Philadelphia. "We are no longer limited by the instability of these molecules and the long timeframe it used to take to manufacture them. These stabilized MHC-I molecules could speed up the screening process and the subsequent development of effective therapies." Led by Sgourakis Lab members Yi Sun, Michael C. Young, and Claire H. Woodward, the researchers stabilized MHC-I molecules by focusing on their 3D structure. Classical MHC-I molecules are comprised of three major parts: a peptide antigen consisting of 8 to 15 amino acids; a light chain that is the same for all MHC-I molecules; and a highly polymorphic heavy chain. In humans, the MHC-I is called human leukocyte antigen, or HLA, which has expanded because of constant evolutionary adaptation in the human population to include more than 35,000 variants, with a variety of different residues located on groove where peptides can bind. Because HLA is so polymorphic, different HLA types display different peptide repertoires, bind different molecular chaperones, and display different T cell receptors (TCRs), which ultimately define immune responses and disease susceptibility. Thus, finding universal targets and immunotherapies that work across the human population has been challenging. To stabilize MHC-I and make it useful for universal peptide loading and screening, the researchers focused on the light chain of the molecule, since it is conserved across HLA types. The light chain performs an important role in stabilizing MHC-I molecules. As soon as the light chain falls off, it triggers the MHC-I molecule to disassemble, at which point it is essentially sent for recycling for future peptide loading, serving as a sort of "on/off" switch for the MHC-I molecule. To exploit this fundamental engineering, the researchers tethered the heavy chain to the light chain, stabilizing the MHC-I in a conformation that is "open" and receptive to peptides. The researchers confirmed the stability of these engineered MHC-I molecules through biophysical characterization, using nuclear magnetic resonance (NMR), showing that their open MHC-I molecules have enhanced stability when loaded with peptides, even those of low to moderate affinity. The researchers also demonstrated that their engineered MHC-I molecules promote peptide exchange across multiple HLA allotypes, covering representatives from five HLA-A, six HLA-B supertypes, and HLA-Ib molecules, which have many different forms. A key component of using this system to enable a high-throughput peptide exchange platform was the design of customized "placeholder" peptides containing unnatural amino acid modifications, which was done in close collaboration with the lab of chemical biologist George Burslem, PhD, at the University of Pennsylvania. "The open MHC-I platform leverages minimal protein modifications to enhance ligand exchange reactions across all known HLA allotypes, as well as oligomorphic MR1 molecules which present aberrant metabolites that are associated with many tumors," Dr. Sgourakis said. "These new molecules could be a versatile tool for screening antigenic epitopes, enabling the detection of low-frequency receptors and engineered antibodies for the development of targeted therapies." This work was supported through grants by NIAID (5R01AI143997), NIDDK (5U01DK112217), and NIGMS (5R35GM125034 and R35GM142505). Additional support was provided through a Fox Chase Cancer Center pilot project grant and NIH grants P30CA006927 and T32GM132039. Sun Y, Young MC, Woodward CH, Danon JN, Truong HV, Gupta S, Winters TJ, Font-Burgada J, Burslem GM, and Sgourakis NG. "Universal open MHC-I molecules for rapid peptide loading and enhanced complex stability across HLA allotypes," Proceedings of the National Academy of Sciences, online June 13, 2023, DOI: 10.1073/pnas.2304055120. About Children's Hospital of Philadelphia: A non-profit, charitable organization, Children's Hospital of Philadelphia was founded in 1855 as the nation's first pediatric hospital. Through its long-standing commitment to providing exceptional patient care, training new generations of pediatric healthcare professionals, and pioneering major research initiatives, the 595-bed hospital has fostered many discoveries that have benefited children worldwide. Its pediatric research program is among the largest in the country. The institution has a well-established history of providing advanced pediatric care close to home through its CHOP Care Network, which includes more than 50 primary care practices, specialty care and surgical centers, urgent care centers, and community hospital alliances throughout Pennsylvania and New Jersey, as well as a new inpatient hospital with a dedicated pediatric emergency department in King of Prussia. In addition, its unique family-centered care and public service programs have brought Children's Hospital of Philadelphia recognition as a leading advocate for children and adolescents. For more information, visit . Contact: Dana Bate Children's Hospital of Philadelphia (267) 426-6055 [email protected] SOURCE Children's Hospital of Philadelphia

Posters and Symposium Highlight Utility of AlloSeq for HLA Typing, Organ Transplant Monitoring and Hematopoietic Stem Cell Monitoring BRISBANE, Calif.--(BUSINESS WIRE)-- CareDx, Inc. (Nasdaq: CDNA), a leading precision medicine company focused on the discovery, development, and commercialization of clinically differentiated, high-value healthcare solutions for transplant patients and caregivers – today announced that it will showcase the latest developments across its AlloSeq®* portfolio during the 36th European Immunogenetics and Histocompatibility Conference taking place April 26-29 in Nantes, France. “We look forward to participating in this meeting and presenting our latest innovations for the European transplant community with our AlloSeq* portfolio of lab products for research and clinical use pre- and post-transplantation,” said Reg Seeto, CEO and President of CareDx. “We are committed to advancing the field of immunogenetics and histocompatibility and take great pride in supporting this important event as a platinum sponsor.” CareDx will be on hand to display its leadership in serving European laboratories, researchers, and clinicians with its best-in-class product portfolio of next-generation sequencing (NGS) based AlloSeq* products, which enables best-in-class care both pre- and post-transplantation. For pre-transplant, CareDx offers AlloSeq Tx* HLA typing solutions. For post-transplant, CareDx offers AlloSeq HCT* chimerism testing and AlloSeq cfDNA* for labs to assess transplanted stem cells and organ health, respectively. CareDx also provides pre-transplant HLA typing and post-transplant surveillance testing for customers through its service lab in Stockholm, Sweden, for clinical research. CareDx will sponsor a symposium “Breaking New Ground: Innovative Pre- and Post-Transplant Solutions to Improve Allograft Outcomes” on Thursday, April 27. The event will be moderated by Curtis Lind, CareDx Vice President and Head of R&D products. Panelists and topics include: Monica Irina Dutescu M,D., Ph.D., National HLA Laboratory, National Institute of Blood Transfusion Prof. Dr. C.T. NICOLAU Bucharest, Romania: High Resolution HLA Typing with AlloSeq Tx – the Experience of National HLA Laboratory, Bucharest. Miguel Alcoceba Ph.D., Department of Haematology, University Hospital of Salamanca (HUS-IBSAL) Salamanca, Spain: Comparison of Next-Generation Sequencing and Short-Tandem Repeats to Monitor Chimerism Analysis. Olivier Aubert M.D., Ph.D., Necker-Enfants Malades Hospital - Paris Transplant Group, Paris, France: dd-cfDNA in Allograft Rejection and Risk Assessment. “I look forward to participating in the CareDx sponsored symposium and showing how its innovative HLA typing solutions represent a strong, efficient, and user-friendly technique for pre-transplant testing, that provides reliable, accurate results. I will also demonstrate how the use of its hybrid capture method can also provide the best coverage, high level of transplant matching and low rates of ambiguity in one product,” said Monica Irina Dutescu, M.D., Ph.D., National Institute of Blood Transfusion, Bucharest. The following nine AlloSeq* oral presentations and posters will be presented at the meeting. Title First Author Poster Featuring AlloSeq Tx17 and Hybrid Capture The expanded role of microRNAs in controlling the HLA class I phenotype: Relationship between the 3’ UTR and post-transcriptional Gene Regulation Panagiotis Mallis Oral Detection of HLA-A and HLA-J haplotype diversity from next-generation sequencing data in commercially available samples. Jessica Edwards P100 Identification of the novel HLA-DPB1*02:01:68 allele in a Greek individual Diamanto Kouniaki P127 Identification of the novel HLA-A*01:426 allele in a Greek individual Diamanto Kouniaki P129 Identification of the novel HLA-A*02:09:01:04 allele in a Greek individual Diamanto Kouniaki P130 Featuring AlloSeq HCT Evaluation of the Magelia for automated purification of CareDx AlloSeq HCT kit libraries in the context of post-hematopoietic stem cells transplantation chimerism assessment Coralie Frassati P124 Featuring AlloSeq cfDNA Assay and Software Clinical relevance of cell-free DNA quantification and qualification during the first month after lung transplantation Pascal Pedini Oral Donor specific HLA-DPw antibodies in a highly sensitized kidney transplant recipient – a case report Dolores Hrusovar P74 Results of the 6 Months Post-Transplant Surveillance in patients transplanted with preformed donor-specific anti-HLA antibodies (DSA) by Adding Donor-Derived Cell-Free DNA Testing María Lasa-Lázaro P121 *AlloSeq Tx, AlloSeq HCT and AlloSeq cfDNA are available as CE/IVD in the EU and in the U.K., and Research Use Only for the rest of the world. AlloSeq Service is available as Research Use Only. Research Use Only products are not to be used for diagnostic procedures. AlloSeq cfDNA is only available outside of the United States. For local regulatory status, please contact CareDx. About CareDx – The Transplant Company CareDx, Inc., headquartered in Brisbane, California, is a leading precision medicine solutions company focused on the discovery, development, and commercialization of clinically differentiated, high-value healthcare solutions for transplant patients and caregivers. CareDx offers testing services, products, and digital healthcare solutions along the pre- and post-transplant patient journey and is the leading provider of genomics-based information for transplant patients. For more information, please visit: CareDx.com. Forward Looking Statements This press release includes forward-looking statements related to CareDx, Inc., including statements regarding the potential benefits and results that may be achieved with CareDx’s AlloSeq* portfolio of lab products, as well as CareDx’s leading participation at the 36th European Immunogenetics and Histocompatibility Conference (the “Participation”). These forward-looking statements are based upon information that is currently available to CareDx and its current expectations, speak only as of the date hereof, and are subject to risks and uncertainties that could cause actual results to differ materially from those projected, including risks that CareDx does not realize the expected benefits of its AlloSeq* portfolio or Participation; general economic and market factors; and other risks discussed in CareDx’s filings with the SEC, including the Annual Report on Form 10-K for the fiscal year ended December 31, 2022 filed by CareDx with the SEC on February 27, 2023 and other reports that CareDx has filed with the SEC. Any of these may cause CareDx’s actual results, performance, or achievements to differ materially and adversely from those anticipated or implied by CareDx’s forward-looking statements. CareDx expressly disclaims any obligation, except as required by law, or undertaking to update or revise any such forward-looking statements. View source version on businesswire.com: Contacts CareDx, Inc. Media Relations Anna Czene 818-731-2203 aczene@caredx.com Investor Relations Greg Chodaczek Investor@caredx.com Source: CareDx, Inc. View this news release online at: