Latest news with #AATD
Yahoo
2 days ago
- Business
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FDA Grants Orphan Drug Status to Beam Therapeutics Inc. (BEAM)' AATD Gene Therapy
Beam Therapeutics Inc. (NASDAQ:BEAM) has secured U.S. FDA orphan drug designation for BEAM-302, its pioneering genetic medicine targeting alpha-1 antitrypsin deficiency (AATD), a rare inherited disorder that can cause severe lung and liver disease. BEAM-302, delivered via liver-targeting lipid nanoparticles, is designed to correct the underlying DNA mutation responsible for AATD, offering hope for a one-time, potentially curative treatment. This regulatory milestone follows the recent Regenerative Medicine Advanced Therapy (RMAT) designation, underscoring the therapy's promise and the urgent need for effective AATD solutions. A biotechnologist in a lab coat discussing a therapeutic antibody with a colleague. Preliminary data from ongoing Phase 1/2 trials show BEAM-302 is well tolerated and achieves dose-dependent, durable correction of the disease-causing mutation, with protein levels exceeding therapeutic thresholds in the 60 mg dose group. Dosing in higher cohorts is underway, with more results from Beam Therapeutics Inc. (NASDAQ:BEAM) expected later in 2025. Orphan drug designation brings significant benefits, including tax credits, user fee exemptions, and up to seven years of market exclusivity post-approval, accelerating development for this first-in-class base editing therapy for AATD, a condition with no current curative treatments. While we acknowledge the potential of BEAM to grow, our conviction lies in the belief that some AI stocks hold greater promise for delivering higher returns and have limited downside risk. If you are looking for an AI stock that is more promising than BEAM and that has 100x upside potential, check out our report about this READ NEXT: and Disclosure: None. Error in retrieving data Sign in to access your portfolio Error in retrieving data Error in retrieving data Error in retrieving data Error in retrieving data
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3 days ago
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Beam Therapeutics Announces U.S. FDA Orphan Drug Designation Granted to BEAM-302 for the Treatment of Alpha-1 Antitrypsin Deficiency (AATD)
CAMBRIDGE, Mass., May 29, 2025 (GLOBE NEWSWIRE) -- Beam Therapeutics Inc. (Nasdaq: BEAM), a biotechnology company developing precision genetic medicines through base editing, today announced that the United States (U.S.) Food and Drug Administration (FDA) has granted orphan drug designation to BEAM-302, a liver-targeting lipid-nanoparticle (LNP) formulation of a guide RNA and an mRNA encoding a base editor designed to correct the disease-causing mutation in patients with alpha-1 antitrypsin deficiency (AATD). AATD is an inherited genetic disorder that affects the lungs and/or liver, leading to early onset emphysema and liver disease, and for which there is significant unmet need for effective therapies that can treat the entire spectrum of disease. 'Receiving orphan drug designation for BEAM-302 is an important milestone in our efforts to bring a transformative therapy to people living with AATD, many of whom currently lack effective long-term treatment options,' said Giuseppe Ciaramella, Ph.D., president of Beam Therapeutics. 'This recognition by the FDA, following the receipt of RMAT designation from the FDA just weeks ago, highlights the urgency of addressing this serious genetic disease and the potential of BEAM-302 to directly correct the DNA mutation, the underlying root cause of this illness. We are encouraged by the FDA's continued support of this program and are committed to its advancement with the goal of delivering a one-time, potentially curative treatment to patients as quickly and safely as possible.' The FDA's orphan drug designation is designed to support the development and evaluation of treatments for rare diseases affecting fewer than 200,000 people in the U.S. The designation comes with potential benefits for the sponsor company, including tax credits for qualified clinical trials, exemption from user fees, and a potential seven years of market exclusivity after approval. Positive initial safety and efficacy data from the ongoing Phase 1/2 trial of BEAM-302, previously reported in March, established clinical proof of concept as a potential treatment for AATD and in vivo base editing. Preliminary results from the first three single-ascending dose cohorts in Part A of the study demonstrated that BEAM-302 was well tolerated, with single doses of BEAM-302 leading to durable, dose-dependent correction of the disease-causing mutation and total AAT protein levels above the therapeutic threshold in the 60 mg dose cohort. Beam has initiated dosing in the fourth cohort of Part A, evaluating 75 mg of BEAM-302, and expects to report updated data at a medical conference in the second half of 2025. Additionally, the company plans to dose the first patient in Part B, which will include AATD patients with mild to moderate liver disease, in the second half of 2025. Beam previously announced the clearance of the U.S. investigational new drug (IND) application for BEAM-302 for the treatment of AATD in March 2025, as well as the granting of Regenerative Medicine Advanced Therapy (RMAT) designation by the FDA to BEAM-302 in May 2025. About BEAM-302BEAM-302 is a liver-targeting lipid-nanoparticle (LNP) formulation of base editing reagents designed to correct the PiZ mutation. Patients homozygous for this mutation (PiZZ) represent the majority of patients living with severe AATD disease. A one-time A-to-G correction of the PiZ mutation with Beam's adenine base editor has the potential to simultaneously reduce the aggregation of mutant, misfolded AAT protein that causes toxicity to the liver (Z-AAT), generate therapeutic levels of corrected protein (M-AAT), and increase total and functional AAT in circulation, thereby addressing the underlying pathophysiology of both the liver and lung disease. In addition, the reduction in circulating PiZ aggregates (i.e., polymers) has the potential to further minimize lung inflammation and dysfunction. Importantly, because the native AAT gene would be corrected in its normal genetic location, AAT levels are anticipated to increase physiologically in response to inflammation or infection. This is a critical aspect of AAT's normal function to regulate the body's inflammatory response, which does not occur with currently approved protein replacement therapies. Correction of the PiZ mutation is expected to be durable based on preclinical and clinical evidence. About Alpha-1 Antitrypsin Deficiency (AATD)AATD is an inherited genetic disorder that can cause early onset emphysema and liver disease. The most severe form of AATD arises when a patient has a point mutation in both copies of the SERPINA1 gene at amino acid 342 position (E342K, also known as the PiZ mutation or the 'Z' allele). This point mutation causes alpha-1 antitrypsin, or AAT, to misfold, accumulating inside liver cells rather than being secreted, resulting in very low levels (10%-15%) of circulating AAT. In addition to resulting in lower levels, the PiZ AAT protein variant is also less enzymatically effective compared to wildtype AAT protein. As a consequence, the lung is left unprotected from neutrophil elastase, resulting in progressive, destructive changes in the lung, such as emphysema, which can result in the need for lung transplants. The mutant AAT protein also accumulates in the liver, causing liver inflammation and cirrhosis, which can ultimately cause liver failure or cancer requiring patients to undergo a liver transplant. It is estimated that approximately 100,000 individuals in the U.S. have two copies of the Z allele, known as the PiZZ genotype, although only about 10% of all patients are thought to have been diagnosed. There are currently no curative treatments approved for patients with AATD, and the only approved therapy in the U.S., intravenous AAT protein replacement, has not been shown to prevent ongoing lung function decline and destruction in patients. About Beam TherapeuticsBeam Therapeutics (Nasdaq: BEAM) is a biotechnology company committed to establishing the leading, fully integrated platform for precision genetic medicines. To achieve this vision, Beam has assembled a platform with integrated gene editing, delivery and internal manufacturing capabilities. Beam's suite of gene editing technologies is anchored by base editing, a proprietary technology that is designed to enable precise, predictable and efficient single base changes, at targeted genomic sequences, without making double-stranded breaks in the DNA. This has the potential to enable a wide range of therapeutic editing strategies that Beam is using to advance a diversified portfolio of base editing programs. Beam is a values-driven organization committed to its people, cutting-edge science, and a vision of providing life-long cures to patients suffering from serious diseases. Cautionary Note Regarding Forward-Looking StatementsThis press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Investors are cautioned not to place undue reliance on these forward-looking statements, including, but not limited to, statements related to: the therapeutic applications and potential of our technology, including with respect to AATD; our plans, and anticipated timing, to advance our BEAM-302 program, including the clinical trial designs and expectations for BEAM-302; our plans to present data at upcoming medical conferences; expectations regarding potential benefits of the orphan drug designation for BEAM-302; and our ability to develop life-long, curative, precision genetic medicines for patients through base editing. Each forward-looking statement is subject to important risks and uncertainties that could cause actual results to differ materially from those expressed or implied in such statement, including, without limitation, risks and uncertainties related to: our ability to develop, obtain regulatory approval for, and commercialize our product candidates, which may take longer or cost more than planned; our ability to raise additional funding, which may not be available; our ability to obtain, maintain and enforce patent and other intellectual property protection for our product candidates; the uncertainty that our product candidates will receive regulatory approval necessary to advance human clinical trials; that preclinical testing of our product candidates and preliminary or interim data from preclinical studies and clinical trials may not be predictive of the results or success of ongoing or later clinical trials; that initiation and enrollment of, and anticipated timing to advance, our clinical trials may take longer than expected; that our product candidates or the delivery modalities we rely on to administer them may cause serious adverse events; that our product candidates may experience manufacturing or supply interruptions or failures; risks related to competitive products; our ability to recognize the potential benefits conferred by the orphan drug designation for BEAM-302; and the other risks and uncertainties identified under the headings 'Risk Factors Summary' and 'Risk Factors' in our Annual Report on Form 10-K for the year ended December 31, 2024, our Quarterly Report on Form 10-Q for the quarter ended March 31, 2025, and in any subsequent filings with the Securities and Exchange Commission. These forward-looking statements speak only as of the date of this press release. Factors or events that could cause our actual results to differ may emerge from time to time, and it is not possible for us to predict all of them. We undertake no obligation to update any forward-looking statement, whether as a result of new information, future developments or otherwise, except as may be required by applicable law. Contacts: Investors:Holly ManningBeam Therapeuticshmanning@ Media:Josie Butler1ABjosie@ in to access your portfolio
Yahoo
5 days ago
- Business
- Yahoo
Citi Downgrades Prime Medicine (PRME) to Neutral, Cuts PT to $1.50 Due to Market Uncertainty
On Tuesday, Citi downgraded Prime Medicine Inc. (NASDAQ:PRME) from a Buy to a Neutral rating while also significantly reducing its price target from $10 to $1.50. Citi said that this adjustment reflects that the company's shares are trading near cash, which shows the market's uncertainty on Prime Medicine's path to potential value inflection. A scientist examining a microchip and circuit board in a hi-tech lab. Despite implementing cost-cutting measures, which include a 25% workforce reduction and prioritizing its liver disease franchise & externally funded programs over Chronic Granulomatous Disease/CGD programs, Prime Medicine's cash reserves are projected to support operations only into H1 2026. This timeline falls short of management's guidance, which anticipates initial in-vivo clinical data for Wilson's disease and Alpha-1 antitrypsin deficiency/AATD in 2027. The company also plans to file an investigational new drug/IND application for these programs in H1 2026 and mid-2026, respectively. Prime Medicine is seeking business development deals to secure non-dilutive capital and extend its financial runway. It continues its cystic fibrosis program, supported by the Cystic Fibrosis Foundation, and collaborates with Bristol Myers Squibb on Prime Edited CAR-T products in hematology, immunology, and oncology. Prime Medicine Inc. (NASDAQ:PRME) is a biotech company that delivers genetic therapies to address the spectrum of diseases by deploying gene editing technology in the US. While we acknowledge the potential of PRME to grow, our conviction lies in the belief that some AI stocks hold greater promise for delivering higher returns and have limited downside risk. If you are looking for an AI stock that is more promising than PRME and that has 100x upside potential, check out our report about the cheapest AI stock. READ NEXT: and . Disclosure: None. This article is originally published at Insider Monkey. Sign in to access your portfolio
Yahoo
19-05-2025
- Business
- Yahoo
Prime Medicine Announces Strategic Restructuring to Focus on Opportunities in Large Genetic Liver Diseases, Cystic Fibrosis, and Partnered Programs Alongside CEO Leadership Transition
-- Initial positive data from Phase 1/2 clinical trial of PM359 in CGD provide clinical proof-of-concept for Prime Editing as a transformative gene editing technology -- -- On-track to file IND and/or CTA for Wilson's Disease and AATD programs in 1H 2026 and mid-2026, respectively; initial clinical data for both expected in 2027 -- -- Allan Reine, M.D., CFO, to succeed Keith Gottesdiener, M.D., as CEO; Jeff Marrazzo, member of the Board of Directors, named Executive Chair -- -- Implementing cost cutting measures to significantly reduce cash needs in advance of key data inflection points -- CAMBRIDGE, Mass., May 19, 2025 (GLOBE NEWSWIRE) -- Prime Medicine, Inc. (Nasdaq: PRME), a biotechnology company committed to delivering a new class of differentiated one-time curative genetic therapies, today announced a strategic restructuring, including the deprioritization of its Chronic Granulomatous Disease (CGD) programs, as well as a cost and workforce reduction to focus on its liver franchise and programs funded through external partnerships. Prime Medicine is currently advancing in vivo programs to cure two of the largest genetic liver diseases, Wilson's Disease and Alpha-1 Antitrypsin Deficiency (AATD), with initial clinical data from both programs expected in 2027. Prime Medicine will also continue its in vivo Cystic Fibrosis program with support from the Cystic Fibrosis Foundation, and its efforts to develop Prime Edited CAR-T products for hematology, immunology and oncology in partnership with Bristol Myers Squibb. In addition, Prime Medicine will continue to pursue additional business development opportunities to accelerate innovation, ensure the broadest application of Prime Editing, and further bolster its financial resources. Also today, Prime Medicine announced that Keith Gottesdiener, M.D., has decided to step down as Chief Executive Officer (CEO) and a member of the Company's Board of Directors, effective immediately. Allan Reine, M.D., Prime Medicine's Chief Financial Officer (CFO), has been named CEO and member of the Board of Directors and Jeff Marrazzo, member of the Company's Board of Directors, has been named Executive Chair. 'The first-in-human data for PM359 announced today represent a landmark moment for the industry and for our company, demonstrating the unequivocal power of Prime Editing to change patients' lives, with a single dose of PM359 providing potentially curative benefit in a matter of weeks,' said Allan Reine, M.D., Chief Executive Officer of Prime Medicine. 'These data also reinforce the critical importance of ensuring Prime Medicine is positioned to withstand the challenges of the current environment, so that we can one day deliver the tremendous promise of Prime Editing to address a wide spectrum of genetic diseases. I am humbled by the opportunity to lead Prime Medicine through this next chapter, and committed to operating with excellence, efficiency and financial discipline as we focus our efforts internally on our Wilson's Disease and AATD programs, where, in the near-term, we have the potential to cure two of the largest genetic liver diseases.' Pipeline Prioritization: Prime Medicine will focus its internal efforts on the development of in vivo programs for the treatment of Wilson's Disease and AATD, two of the largest genetic liver diseases. Prime Medicine expects to file an investigational new drug (IND) and/or clinical trial application (CTA) for its Wilson's Disease program in the first half of 2026 and for its AATD program in mid-2026; initial clinical data from both programs are expected in 2027. Wilson's Disease: Wilson's Disease is a rare and severe disorder caused by excess copper accumulation in the liver and brain that can lead to liver failure and neurocognitive decline and can be fatal without a liver transplant. There are currently no approved disease-modifying therapies for Wilson's Disease, which affects more than 20,000 people in the United States and European Union. AATD: AATD is a progressive, genetic disorder caused by mutations in the SERPINA1 gene, which can result in both lung- and liver-related symptoms, including shortness of breath, wheezing, chronic cough and frequent chest colds, as well as jaundice, ascites, and cirrhosis. There are currently no disease-modifying or curative treatments approved for the approximately 200,000 people in the United States and European Union with AATD, of which 20,000-30,000 people are currently diagnosed. Many patients with AATD ultimately progress to liver failure or severe lung disease, eventually resulting in premature death. Prime Medicine will also continue its in vivo Cystic Fibrosis program with support from the Cystic Fibrosis Foundation, and its efforts to develop Prime Edited CAR-T products for hematology, immunology and oncology in partnership with Bristol Myers Squibb. As announced in conjunction with initial data for PM359 this morning, Prime Medicine is exploring options for the continued clinical development of PM359 external to the company and ceasing further efforts in X-linked CGD. Prime Medicine believes PM359 has the potential to transform the care of p47phox CGD and is committed to working with urgency to identify an appropriate partner to help ensure this important therapy is delivered to patients. Management and Corporate Update Management Update: The Board of Directors has appointed Dr. Reine, Prime Medicine's CFO, as CEO and member of the Board of Directors, effective immediately. Additionally, Jeff Marrazzo, member of the Board of Directors, has been named as Executive Chair. Dr. Reine is a seasoned executive with more than twenty years' experience in the biotechnology industry. Prior to joining Prime Medicine in 2024, Dr. Reine was CFO at Foghorn Therapeutics and, before that, at Pieris Pharmaceuticals. Previously, Dr. Reine spent fifteen years as a healthcare investor managing various healthcare portfolios primarily focused on biotechnology and pharmaceutical companies. In addition, Dr. Reine started his career in biotechnology investment banking and sell-side research. Dr. Reine also serves as Chairman of the Board of ONK Therapeutics. Mr. Marrazzo joined the Prime Medicine Board of Directors in 2023. Prior to that, he founded and built Spark Therapeutics into the world's first fully integrated, commercial gene therapy company, and successfully orchestrated its $4.8 billion sale to Roche in 2019. Under his leadership, Spark developed and launched LUXTURNA® for a rare blinding disorder, the first U.S. Food and Drug Administration (FDA)-approved gene therapy for a genetic disease in the U.S., developed BEQVEZ™, which was licensed to Pfizer and approved by the FDA for hemophilia B, and advanced multiple programs into Phase 3, including several which received Breakthrough Designation. 'The selection of Allan as Prime Medicine's next CEO is the result of thoughtful succession planning, designed to position the company for long-term success, while maintaining the culture of innovative thinking, scientific rigor and collaboration that has always defined the organization and that will continue to fuel its long-term growth,' said Mr. Marrazzo. 'As a seasoned CFO, former investor and physician, Allan brings a combination of financial and scientific acumen, which will enable him to champion and advance Prime Medicine's pipeline, while ensuring the company can successfully navigate the evolving market conditions. I look forward to working closely together as he assumes this new role.' Mr. Marrazzo continued, 'Since its discovery in 2019, Keith has been an incredible advocate for Prime Editing. He was early to recognize the transformative power of this new technology and built Prime Medicine to enable its rapid development. With the announcement of positive initial data for PM359, and the changes in the company as part of the strategic prioritization, today marks a natural time to transition leadership of Prime Medicine. On behalf of the Board, I thank Keith for his visionary leadership and wish him the very best in his next professional endeavor.' Dr. Gottesdiener will continue to support Prime Medicine as a consultant for a period of one year. Corporate Update: Alongside the pipeline prioritization announced today, Prime Medicine is undertaking cost reduction measures and restructuring its team, including reducing its organizational headcount by approximately 25% percent. These initiatives are designed to significantly decrease Prime Medicine's operating expenses and cash burn, reducing anticipated cash needs by almost half through 2027. Dr. Reine added, 'I am deeply grateful to the employees who will be impacted as part of this restructuring. They all contributed mightily to advancing Prime Editing from concept to clinic, and their efforts across research and development and broader company-building will serve as the foundation for our success for many years to come. Importantly, while today's restructuring positions Prime Medicine to efficiently execute towards potentially transformative inflection points in Wilson's Diseases and AATD, we remain unwavering in our long-term ambition to realize the full promise of Prime Editing for a wide spectrum of diseases.' Also today, Prime Medicine announced that it recently engaged in binding arbitration proceedings with Beam Therapeutics, Inc. regarding the parties' 2019 Collaboration and License Agreement (the 'Agreement') and specific to its AATD program. Prime Medicine is committed to honoring the terms of the Agreement, and confident that it has the rights to pursue AATD under the Agreement. Based on its current plans, Prime Medicine continues to expect that its cash, cash equivalents and investments as of March 31, 2025 will be sufficient to fund its operations and capital expenditure requirements into the first half of 2026. About Prime Medicine Prime Medicine is a leading biotechnology company dedicated to creating and delivering the next generation of gene editing therapies to patients. The Company is deploying its proprietary Prime Editing platform, a versatile, precise and efficient gene editing technology, to develop a new class of differentiated one-time curative genetic therapies. Designed to make only the right edit at the right position within a gene while minimizing unwanted DNA modifications, Prime Editors have the potential to repair almost all types of genetic mutations and work in many different tissues, organs and cell types. Taken together, Prime Editing's versatile gene editing capabilities could unlock opportunities across thousands of potential indications. Prime Medicine is currently progressing a diversified portfolio of investigational therapeutic programs organized around our core areas of focus: liver, lung, and immunology and oncology. Across each core area, Prime Medicine is focused initially on a set of high value programs, each targeting a disease with well-understood biology and a clearly defined clinical development and regulatory path, and each expected to provide the foundation for expansion into additional opportunities. Over time, the Company intends to maximize Prime Editing's broad and versatile therapeutic potential, as well as the modularity of the Prime Editing platform, to rapidly and efficiently expand beyond the diseases in its current pipeline, potentially including additional genetic diseases, immunological diseases, cancers, infectious diseases, and targeting genetic risk factors in common diseases, which collectively impact millions of people. For more information, please visit © 2025 Prime Medicine, Inc. All rights reserved. PRIME MEDICINE, the Prime Medicine logos, and PASSIGE are trademarks of Prime Medicine, Inc. All other trademarks referred to herein are the property of their respective owners. Forward Looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including, without limitation, implied and express statements about Prime Medicine's beliefs and expectations regarding: the continued development and advancement of its AATD and Wilson's Disease programs, including the timing of the filing of IND and/or CTA applications in mid-2026 and 1H 2026, respectively, and the timing of initial data for both programs in 2027; the initiation, timing, progress, and results of its research and development programs, preclinical studies and future clinical trials, including the release of data related thereto; the potential of Prime Editing to correct the causative mutations of diseases, including of AATD, Wilson's Disease and CF; the breadth of Prime Editing technology and the implementation of its strategic plans for its business, programs, and technology; the potential of Prime Editing as a transformative gene editing technology and its ability to unlock opportunities across thousands of potential indications; its ability to identify an external partner to deliver PM359 therapy in X-linked CGD to patients; its rights to pursue AATD using its approach in connection with the arbitration proceedings with Beam Therapeutics, Inc.; and its expected cash runway. Any forward-looking statements in this press release are based on management's current expectations and beliefs and are subject to a number of risks, uncertainties and important factors that may cause actual events or results to differ materially from those expressed or implied by any forward-looking statements contained in this press release, including, without limitation, risks associated with: uncertainties related to Prime Medicine's product candidates entering clinical trials; the authorization, initiation, and conduct of preclinical and IND-enabling studies and other development requirements for potential product candidates, including uncertainties related to opening INDs and obtaining regulatory approvals; risks related to the development and optimization of new technologies, the results of preclinical studies, or clinical studies not being predictive of future results in connection with future studies; the scope of protection Prime Medicine is able to establish and maintain for intellectual property rights covering its Prime Editing technology; Prime Medicine's ability to identify and enter into future license agreements and collaborations; Prime Medicine's expectations regarding the anticipated timeline of its cash runway and future financial performance; and general economic, industry and market conditions. These and other risks and uncertainties are described in greater detail in the section entitled 'Risk Factors' in Prime Medicine's most recent Annual Report on Form 10-K, as well as any subsequent filings with the Securities and Exchange Commission. In addition, any forward-looking statements represent Prime Medicine's views only as of today and should not be relied upon as representing its views as of any subsequent date. Prime Medicine explicitly disclaims any obligation to update any forward-looking statements subject to any obligations under applicable law. No representations or warranties (expressed or implied) are made about the accuracy of any such forward-looking statements. Investor and Media Contacts Gregory DearbornPrime Medicine857-209-0696gdearborn@ Hannah DeresiewiczPrecision
Yahoo
17-05-2025
- Health
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Tessera Therapeutics Features New Preclinical Data Demonstrating Progress Across its In Vivo Gene Writing™ Programs and Delivery Platform at the American Society of Gene and Cell Therapy 28th Annual Meeting
Presented new preclinical data in non-human primates (NHP) for alpha-1 antitrypsin deficiency (AATD) and phenylketonuria (PKU), where RNA Gene Writer achieved an estimated 76% and 70% editing in hepatocytes1, respectively New AATD data reinforced the safety and precision of Tessera's proprietary LNP delivery system, demonstrating that it was well tolerated in NHP with high liver specificity and no off-target activity detected Preclinical data for sickle cell disease (SCD) across mouse and NHP models highlight Tessera's RNA Gene Writers' ability to drive durable and efficient gene editing greater than 20% in long-term hematopoietic stem cells (LT-HSCs), reaching a potentially curative threshold SOMERVILLE, Mass., May 17, 2025 (GLOBE NEWSWIRE) -- Tessera Therapeutics, the biotechnology company pioneering a new approach in genetic medicine known as Gene Writing™, is presenting updates across its in vivo genetic medicine programs for AATD, PKU, and SCD, as well as advances in in vivo T cell therapies. These data were shared across four oral presentations and three poster presentations at the American Society of Gene and Cell Therapy (ASGCT) Annual Meeting taking place in New Orleans, Louisiana, May 13 – 17, 2025. 'The ability to achieve durable, highly efficient gene editing in vivo – including in the liver, hematopoietic stem cells, and T cells – positions Tessera to address multiple disease areas,' said Michael Severino, M.D., CEO of Tessera Therapeutics. 'As we move closer to the clinic, these results underscore the potential of our Gene Writing and delivery platforms to advance a new class of genetic medicines that could one day transform the treatment of AATD, PKU, and SCD, and oncologic and autoimmune diseases.' AATD Data AATD is a monogenic disease of the liver caused by mutations in the SERPINA1 gene, resulting in an abnormal form of the alpha-1 antitrypsin (AAT) protein that causes both lung and liver manifestations. Preclinical data in NHPs following a single dose of 1.5 mg/kg of RNA Gene Writer formulated with a proprietary LNP delivery vehicle, continued to show robust levels of genome editing, achieving an estimated 76% in hepatocytes1 at the SERPINA1 locus. High fidelity was observed with a 195 to 1 ratio of intended to unintended edits at the target locus. As part of Tessera's evaluation of the genomic safety profile of its RNA Gene Writer, NHP data displayed high specificity of editing to the liver with only spleen showing quantifiable levels of editing above background (0.14%) among 30 additional tissues tested. Importantly, editing was not detected in germline tissues, including testes and ovaries. Editing was also highly specific to the intended SERPINA1 locus, with no off-target activity detected at other genetic loci. In addition, a study in NHPs where 80% editing of hepatocytes was achieved by an RNA Gene Writer targeting SERPINA1 demonstrated this editing was durable for at least six months, as supported by genomic DNA analysis of whole liver samples and cDNA analysis of edited mRNA transcripts. Data were also presented from an RNA Gene Writer that achieved therapeutically relevant levels of correction at very low doses in the PiZ mouse model, including 70% genomic correction in hepatocytes at 0.05 mg/kg, and 95% at 0.5 mg/kg that corresponded to 92% and 100% correction of serum AAT protein to wild-type. Durable mutation correction and phenotypic rescue was observed including a 75% reduction of AAT aggregates by liver histology that resulted in less than 5% of liver area being occupied by toxic aggregates in the 0.5 mg/kg treated group at 10 weeks post-treatment. Further data featured on Tessera's proprietary LNP delivery vehicle demonstrated that it was well tolerated in NHPs, with no clinically meaningful elevation in liver enzyme levels and no signs of coagulopathy at doses of 1 and 2 mg/kg. PKU Data PKU is a monogenic disease of the liver caused by mutations in the phenylalanine hydroxylase (PAH) gene, which leads to the inability to metabolize the dietary amino acid phenylalanine (Phe), resulting in toxic Phe accumulation and neurocognitive impairment. Preclinical data in NHPs was presented from a single dose of RNA Gene Writer formulated with a proprietary LNP delivery vehicle, where an estimated 70% editing of the PAH locus was achieved in hepatocytes1 at 2 mg/kg, with supporting cDNA analysis demonstrating 67% of PAH mRNA was edited. Data was also presented from an RNA Gene Writer that achieved an estimated 65% correction in hepatocytes at 0.2 mg/kg in the humanized R408W mouse model, normalizing plasma Phe levels in a mouse disease model. SCD Data SCD is the most common lethal monogenic disease globally, arising from a mutation in the hemoglobin beta-globin (HBB) gene that results in hemoglobin S, which can cause red blood cell sickling, acute and chronic pain, and widespread organ damage. Multiple proof-of-concept studies of Gene Writer formulated in a proprietary LNP delivery vehicle were presented, achieving greater than 20% HBB editing in LT-HSCs with repeat dose in two NHP species, including cynomolgus and rhesus, reaching potentially curative levels. Single cell analysis of HSCs collected from treated NHP showed ~35-50% of cells had at least one edited HBB gene. Edited cells demonstrated durability across multiple loci in NHP, out to 6 months with beta-2 microglobulin (B2M) surrogate editing and out to 4 months with HBB editing, with edited cells supporting long-term self-renewal and multi-lineage development. In a humanized mouse model engrafted with mobilized peripheral blood cells from individuals with SCD, RNA Gene Writer achieved approximately 35% in vivo correction of the HBB gene in LT-HSCs. Additional data in a humanized wild-type mouse model showed that RNA Gene Writer achieved greater than 50% HBB editing in LT-HSCs across multiple donors. These results across mouse and NHP models highlight Tessera's Gene Writing and delivery platforms' ability to drive efficient gene correction in clinically relevant cell populations, representing a significant advancement towards a potentially curative, durable and non-viral approach for treating SCD that will neither require stem cell mobilization/transplantation nor myeloablative pre-conditioning. Human mixed donor chimerism studies demonstrate that 20% chimerism can reverse the sickle phenotype in patients following allogeneic hematopoietic stem cell transplant.2 Advances Towards T-Cell Therapies Tessera is applying its Gene Writing and proprietary LNP delivery platforms to develop in vivo cell therapies for potential oncology and autoimmune disease applications. Proof-of-concept mouse studies demonstrated that a single intravenous infusion of RNA Gene Writer, delivered in a proprietary LNP, successfully generated functional CAR-T cells in vivo targeting CD19 and CD20. In a tumor-bearing xenograft model, this approach led to CD19 CAR-T cell expansion and complete tumor clearance. In a naïve humanized mouse model, an average of 30% CD20-targeted CAR writing was achieved in resting T cells, resulting in the elimination of circulating human B cells. ___________________1 Based on the assumption that 60% of liver cells are comprised of hepatocytes2 Blood. 2017;130(17):1946-1948 About Tessera Therapeutics Tessera Therapeutics is pioneering a new approach to genome engineering through the development of its Gene Writing™ and delivery platforms, with the aim to unlock broad new therapeutic frontiers. Our Gene Writing platform is designed to write therapeutic messages into the genome by efficiently changing single or multiple DNA base pairs, precisely correcting insertions and deletions, or adding exon-length sequences and whole genes. Our proprietary lipid nanoparticle delivery platform is designed to enable the in vivo delivery of RNA to targeted cell types. We believe our Gene Writing and delivery platforms will enable transformative genetic medicines to not only cure diseases that arise from errors in a single gene, but also modify inherited risk factors for common diseases and create engineered cells to treat cancer and potentially autoimmune and other diseases. Tessera Therapeutics was founded in 2018 by Flagship Pioneering, a life sciences innovation enterprise that conceives, creates, resources, and develops first-in-category bioplatform companies to transform human health and sustainability. For more information about Tessera, please visit ContactJonathan PappasLifeSci Communications, LLCjpappas@ while retrieving data Sign in to access your portfolio Error while retrieving data Error while retrieving data Error while retrieving data Error while retrieving data
