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SANTA FE, N.M.--( BUSINESS WIRE )--Be Biopharma, Inc. (“Be Bio”), a company pioneering the development of engineered B Cell Medicines (BCMs), today announced an oral presentation and poster presentation at the Keystone Symposia on Emerging Cellular Therapies meeting, held from January 22 to 25, 2024 in Santa Fe, New Mexico. The data being presented support the utility of engineered B cell medicines (BCMs) across a broad range of applications. Together, the data demonstrate in vitro production and activity of several therapeutic proteins, as well as i n vivo engraftment without preconditioning and activity in multiple model systems. “Gene and cell therapies have transformative potential to treat previously intractable diseases, but have barriers to adoption such as lack of durability, inability to re-dose, and requirement of preconditioning for engraftment. Our BCM platform has the potential to address these barriers,” said Richard A. Morgan, Ph.D., Chief Scientific Officer, Be Bio. “The in vivo preclinical data presented today validates key attributes of our BCM platform – efficient protein production, editing and insertional efficiency, and durable protein production without preconditioning – while demonstrating its potential therapeutic benefits in genetic disease and cancer.” Presentation Summary: Development of an Ex Vivo Precision Gene Engineered B Cell Medicine Platform that Produces Active and Sustained Levels of Therapeutic Proteins with Broad Utility BCMs were produced via a precision genome engineering platform that achieves gene knockouts with greater than 90% efficiency and targeted HDR-mediated gene insertions at up to 60%. Modularity of the BCM platform was demonstrated across multiple models and proteins, including production of firefly luciferase, lysosomal storage disease enzyme acid sphingomyelinase, an anti-CD19/CD3 bispecific T cell engager, clotting factor IX, and fusion protein of tissue nonspecific alkaline phosphatase (ALP). These examples demonstrate that these BCMs can produce proteins with enzyme specific activity higher than recombinant proteins (ASM), show efficacy in tumor treatment (anti-CD19/CD3 scFv), and are stably expressed for at least 20 weeks in vivo (FIX). Engraftment in all models was achieved without preconditioning which broadens BCM clinical utility for patients for whom preconditioning toxicities are unacceptable or outweigh therapeutic benefit, and could facilitate additional rounds of treatment as needed. BCMs capable of expressing therapeutically relevant transgenes have the potential for broad and meaningful therapeutic utility in genetic diseases, cancer, and beyond. Details for the oral presentation of this study are as follows: Title: “Development of an Ex Vivo Precision Gene Engineered B Cell Medicine Platform that Produces Active and Sustained Levels of Therapeutic Proteins with Broad Utility” Lead Author: Hanlan Liu, Ph.D., MBA, Senior VP, Pipeline and Non-clinical Development, Be Biopharma Presenter: Hanlan Liu, Ph.D., MBA, Senior VP, Pipeline and Non-clinical Development, Be Biopharma Date/Time: Tuesday, January 23, 2024, 5:00-7:00pm (MST) Session: Strategies for Engineered Cell Therapies Poster Summary: Development of an Ex Vivo Precision Gene Engineered B Cell Medicine Platform that Produces Active and Sustained Levels of Therapeutic Proteins with Broad Utility in Rare Diseases and Cancer This study demonstrates production of BCMs via editing, expansion and differentiation of primary human B cells. Cells engineered to express firefly luciferase were engrafted into NOG-hIL6 mice and demonstrated in vivo persistence for 125 days. Data are also presented on BCMs engineered to produce FIX, which demonstrates activity via the chromogenic and aPTT assay. These BCMs were engrafted into NOG-hIL6 mice and demonstrate durable FIX secretion to 168 days. In addition to FIX, BCMs were engineered to produce an anti-CD19/CD3 bispecific T cell engager, which demonstrated potent activity in an in vivo PdX model of ALL, ALP, which corrected HPP-related bone mineralization deficits in vitro , and ASM, which demonstrated in vitro phenotypic correction in SMPD1 knockout cells. In addition, ex vivo -rhesus macaque plasma cells were generated and labeled with a radioactive tracer. These cells were administered without preconditioning and demonstrated homing to and engraftment in plasma cell niches in an autologous rhesus macaque. Details for the poster presentation of this study are as follows: Title: “Development of an Ex Vivo Precision Gene Engineered B Cell Medicine Platform that Produces Active and Sustained Levels of Therapeutic Proteins with Broad Utility in Rare Diseases and Cancer” Lead Author: Hanlan Liu, Ph.D., MBA, Senior VP, Pipeline and Non-clinical Development, Be Biopharma Presenter: Hanlan Liu, Ph.D., MBA, Senior VP, Pipeline and Non-clinical Development, Be Biopharma Poster #: 2 Poster Session: Wednesday, January 24, 2024, 7:30pm (MST) About Engineered B Cell Medicines – A New Class of Cellular Medicines The B cell is a powerful cell that produces thousands of proteins per cell per second at constant levels, over decades. Precision genome editing can now be used to engineer B Cells that produce therapeutic proteins of interest, driving a new class of cellular medicines – Engineered B Cell Medicines (BCMs) – with the potential to be durable, allogeneic, redosable and administered without pre-conditioning. The promise of BCMs could transform therapeutic biologics with broad application — across protein classes, patient populations and therapeutic areas. About Be Biopharma Be Biopharma (“Be Bio”) is pioneering Engineered B Cell Medicines (BCMs) to dramatically improve the lives of patients who are living with Hemophilia B and other genetic diseases, cancer, and other serious conditions. With eyes locked on the patient, our team of purpose-driven scientists, technologists, manufacturing experts and business builders collaborate to create a bold new class of cell therapies. Be Bio was founded in October 2020 by B cell engineering pioneers David Rawlings, M.D., and Richard James, Ph.D., from Seattle Children’s Research Institute. Be Bio is backed by ARCH Venture Partners, Atlas Venture, RA Capital Management, Alta Partners, Longwood Fund, Bristol Myers Squibb, Takeda Ventures, Seattle Children’s Research Institute and others. Since our founding, Be Bio’s investors have committed over $180 million to enable the Company to re-imagine medicine based on the power of B cell therapy. For more information, please visit us at Be.Bio and our LinkedIn page.

Ilofotase alfa demonstrates pharmacologically relevant effect on disease specific biomarkers and a positive safety pro adult patients with hypophosphatasia; Data to be presented by Lothar Seefried, MD, at the American Society for Bone and Mineral Research’s Symposium on Rare Bone Diseases on Thursday, October 12, 2023 UTRECHT, The Netherlands--(BUSINESS WIRE)-- AM-Pharma B.V. today announced positive clinical results from the Phase 1b study evaluating the company’s proprietary recombinant alkaline phosphatase, ilofotase alfa, as potential enzyme replacement therapy in adult hypophosphatasia (HPP) patients. HPP is an inherited metabolic disease, characterized by low activity of tissue non-specific alkaline phosphatase (TNAP), caused by mutations at the ALPL gene. This low activity leads to accumulation of inorganic pyrophosphate (PPi), a strong inhibitor of mineralization, as well as pyridoxal-5’-phosphate (PLP), an important cofactor for enzymes. The disease can range widely in severity, however most adults with HPP suffer from recurrent fractures, muscle weakness, joint diseases and pain.1 In the open-label pilot trial, a total of 12 patients were randomly assigned to one of two treatment arms and received a single intravenous dose of either 0.8 mg/kg or 3.2 mg/kg. Patients were followed for 10 days after dosing to evaluate changes in the biochemical fingerprint of HPP, safety and tolerability. The primary objectives for the study were changes in serum levels of PLP and PPi as compared to baseline. For PLP, the maximum proportional reduction was 35% in the 0.8 mg/kg cohort and 66% in the 3.2 mg/kg cohort. The mean time to return to 90% of baseline was 55 hours in the low-dose cohort and 168 hours in the high-dose cohort. The maximal proportional reduction for PPi was 36% in the 0.8 mg/kg cohort and 77% in the 3.2 mg/kg cohort. The mean time to return to 90% of baseline was 9.3 hours in the low-dose cohort and 53 hours in the high-dose cohort. In addition, ilofotase alfa was well-tolerated with pharmacokinetics consistent with observations from previous clinical studies. “The pronounced effect on all HPP disease relevant biomarkers together with a positive safety and tolerability profile, consistent with previous clinical studies with ilofotase alfa, supports its further development as a treatment option for adult HPP patients who are currently underserved,” said Juliane Bernholz, PhD, Chief Executive Officer of AM-Pharma. The full dataset will be presented at the American Society for Bone and Mineral Research – Rare Bone Disease Alliance (ASBMR-RBDA) Symposium at the Vancouver Convention Centre in Vancouver, BC, Canada. The presentation by Lothar Seefried, MD, from the University of Wuerzburg, lead investigator of the trial, is scheduled for 3:00 pm PDT on Thursday, October 12, 2023, in session III: Latest in Clinical Trials. "Considering the wide range of clinical manifestations of HPP, there's an unequivocal need to expand therapeutic opportunities for these patients," added Lothar Seefried, MD. "The encouraging early results confirming dose-dependent reductions of PLP and PPi levels upon treatment with ilofotase alfa underline the compound's therapeutic potential in that indication and I'm looking forward to evaluating ilofotase alfa in next stage clinical studies." About ilofotase alfa Ilofotase alfa is a proprietary recombinant alkaline phosphatase, constructed from two human isoforms of alkaline phosphatase, that has been shown to be stable and highly active in multiple clinical trials. The recombinant enzyme displays exquisite activity towards dephosphorylating and detoxifying damage-associated molecular patterns (DAMPs) and pathogen-associated molecular patterns (PAMPs) such as lipopolysaccharide (LPS), ATP, ADP and other extracellular substrates that drive acute inflammation, coagulation and microvascular ischemia found in kidney following sepsis or ischemia-induced damage. Research has shown that ATP dephosphorylation has a double effect in protecting against kidney injury. When the pro-inflammatory ATP is dephosphorylated, the resulting adenosine further reduces inflammation through the activation of the immunosuppressive adenosine A2a receptor pathway. In hypophosphatasia, ilofotase alfa addresses elevated levels of pyridoxal-5′-phosphate (PLP), inorganic pyrophosphates (PPi), two disease related biomarkers that are related to, for example, bone mineralization and pain sensation. About hypophosphatasia HPP is a rare inherited disease characterized by a deficiency in alkaline phosphatase which is essential for bone mineralization and general functions. HPP patients of all ages can exhibit a wide variety of symptoms that worsen overtime, including bone injury, severe muscle pain and weakness. The disease can also lead to life-threatening complications in infants. The US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) granted AM-Pharma Orphan Drug Designation (ODD) for ilofotase alfa in HPP. In preclinical models, ilofotase alfa was able to achieve improved overall survival of severe disease, as well as restoration of phenotypes associated with HPP. About AM-Pharma AM-Pharma strives to develop medicines for patients confronted with severe medical conditions. Our proprietary asset, ilofotase alfa, is being developed for the treatment of patients with acute kidney injury and has been granted FDA fast-track status. We also develop ilofotase alfa in the severe rare disease hypophosphatasia where ilofotase alfa has orphan drug status in the US and EU. With approximately 1,000 subjects evaluated to date in clinical trials, ilofotase alfa has a proven safety pro a demonstrated kidney benefit. We are a dedicated team driven to bring treatment options to severely ill patients, their families and acute care professionals. Find out more about us online at: . 1 Tournis, S., Yavropoulou, M. P., Polyzos, S. A., & Doulgeraki, A. (2021). Hypophosphatasia. Journal of Clinical Medicine, 10(23), 5676. View source version on businesswire.com: Contacts Investors: Juliane Bernholz, Chief Executive Officer j.bernholz@am-pharma.com Media: Trophic Communications Eva Mulder or Priscillia Perrin +31 6 52 33 15 79 am-pharma@trophic.eu Source: AM-Pharma View this news release online at:

NEW YORK and BASEL, Switzerland, Sept. 20, 2021 /PRNewswire/ -- Aruvant Sciences, a private company focused on developing gene therapies for rare diseases, today announced that data on ARU-2801, a potentially curative gene therapy for people living with hypophosphatasia (HPP), will be highlighted in two poster presentations at the American Society for Bone and Mineral Research (ASBMR) 2021 Annual Meeting which is taking place in person and virtually from October 1 to October 4, 2021. ARU-2801 is a one-time, adeno-associated virus (AAV) gene therapy designed to deliver potentially curative efficacy to patients with HPP without the limitations of chronic administration. Preclinical research shows treatment with ARU-2801 results in sustained elevation of tissue non-specific alkaline phosphatase (TNAP), the missing enzyme in HPP, at levels that ameliorate disease symptoms. Manufacturing process development and Investigational New Drug application-enabling studies are currently underway. "The data being presented at ASBMR support the development of ARU-2801 as a new, one-time treatment option for patients with HPP," said Will Chou, M.D., chief executive officer of Aruvant. "Given the chronic nature and injection site issues associated with the current standard of care, there is a substantial unmet need that we are focused on addressing with ARU-2801." The preclinical study presented by Dr. Koichi Miyake's laboratory at Nippon Medical School examined the use of ARU-2801 administered as a single injection in a murine model for severe infantile HPP and its ability to improve bone maturation and long-term survival. The treated mice exhibited high plasma alkaline phosphatase activity, normal function and behavior throughout their lives and lived for the duration of the study, which was up to 18 months after injection. The study conducted in the laboratory of Dr. José Luis Millán, professor in the Human Genetics Program at Sanford Children's Health Research Center, showed ARU-2801 extended the lifespan of the HPP mice and showed improved dentoalveolar phenotypes. Both studies showed no evidence of ectopic or vascular calcifications with the therapeutic doses used in treated HPP mice. Data from both studies suggests that using ARU-2801, an AAV gene therapy, may provide durable clinical benefit to HPP patients after a single injection. Presentation Information Poster Title:  Successful adeno-associated virus mediated neonatal gene therapy treatment of a murine model of infantile hypophosphatasia resulted in bone maturation and increased survival to at least 18 months. Time: The data will be presented on Friday, October 1, from 5:00 PM to 6:30 PM PT. An additional live virtual chat will occur on Sunday, October 3, from 1:00 PM to 2:00 PM PT. Abstract: The abstract (VPL-412) can be found here in the program. Poster Title: Adeno-associated virus TNAP-D10-mediated gene therapy improves skeletal and dentoalveolar phenotypes in Alpl-/- mice Time: The data will be presented on Friday, October 1, from 5:00 PM to 6:30 PM PT. Abstract: The abstract (VPL-410) can be found here in the program. About Aruvant Sciences Aruvant Sciences, part of the Roivant family of companies, is a clinical-stage biopharmaceutical company focused on developing and commercializing gene therapies for the treatment of rare diseases. The company has a talented team with extensive experience in the development, manufacturing and commercialization of gene therapy products. Aruvant has an active research program with a lead product candidate, ARU-1801, in development for individuals suffering from sickle cell disease (SCD). ARU-1801, an investigational lentiviral gene therapy, is being studied in a Phase 1/2 clinical trial, the MOMENTUM study, as a one-time potentially curative treatment for SCD. Preliminary clinical data demonstrate engraftment of ARU-1801 and amelioration of SCD is possible with one dose of reduced intensity chemotherapy. The company's second product candidate, ARU-2801, is in development to cure hypophosphatasia, a devastating, ultra-orphan disorder that affects multiple organ systems and leads to high mortality when not treated. Data from pre-clinical studies with ARU-2801 shows durable improvement in disease biomarkers and increased survival. For more information on the ongoing ARU-1801 clinical study, please visit and for more on the company, please visit . Follow Aruvant on Facebook, Twitter @AruvantSciences and on Instagram @Aruvant_Sciences.