Precision BioSciences, Inc.

– Clinical Trial Application accepted in Moldova with additional regulatory applications pending approval – PBGENE-HBV is the first in vivo gene editing program for chronic hepatitis B virus to move into global clinical trials – Company to host investor event highlighting clinical candidate safety data and plans for the Phase 1 trial prior to American Association for the Study of Liver Diseases Annual Meeting DURHAM, NC, USA I October 24, 2024 I Precision BioSciences, Inc. (Nasdaq: DTIL), a clinical stage gene editing company utilizing its novel proprietary ARCUS ® platform to develop in vivo gene editing therapies for sophisticated gene edits, today announced that it has received Clinical Trial Application (CTA) approval in Moldova for its lead candidate, PBGENE-HBV. PBGENE-HBV is Precision’s wholly owned in vivo gene editing program designed to cure chronic hepatitis B by eliminating cccDNA, the key source of replicating hepatitis B virus (HBV), while also inactivating integrated HBV DNA in hepatocytes. The company has opened the Phase 1 clinical program and is moving towards dosing patients. “At Precision, we remain laser-focused on execution, and our first CTA approval for PBGENE-HBV represents another significant milestone as we complete our transition to a clinical stage in vivo gene editing company. With rapid regulatory approval in hand, we are working diligently to screen and dose patients at our first clinical site in Moldova,” said Michael Amoroso, Chief Executive Officer of Precision BioSciences. “In parallel, we are leveraging our robust regulatory package, which highlights the safety and potent antiviral effects of PBGENE-HBV in a variety of models, including non-human primates, to pursue additional CTA and IND approvals globally. This multi-track approach will enable us to accelerate enrollment into the trial and generate important clinical safety and efficacy data with the aim of bringing a potentially curative treatment to the nearly 300 million patients living with chronic hepatitis B globally.” Prior to PBGENE-HBV, no other modality has been investigated in a clinical trial setting that is designed to eliminate the root cause of disease, the cccDNA. Additionally, the current standard of care requires daily chronic treatment with nucleos(t)ide analogs and only offers patients a 1-3% chance of functional cure. Through its precision cutting, compact design, and simple structure, PBGENE-HBV is engineered to target the HBV viral genome and drive functional cures for patients with chronic hepatitis B. PBGENE-HBV leverages the ARCUS ® gene editing platform by delivering an ARCUS nuclease-encoding mRNA to the liver via lipid nanoparticles. When expressed in HBV-infected hepatocytes, the ARCUS nuclease specifically cuts a highly conserved sequence in the hepatitis B viral genome and is designed to eliminate cccDNA and inactivate integrated HBV genomes. The ARCUS platform is derived from a naturally occurring enzyme and has been optimized for over 20 years into a ground-breaking and highly precise gene editing tool. “We are thrilled to receive CTA approval in Moldova given the high prevalence of chronic hepatitis B in the country and their expertise gained from multiple Phase 1 clinical trials in hepatitis B. Our clinical team, guided by our hepatitis scientific advisory board, has deep expertise in hepatitis B, and we believe that we are well-positioned to advance PBGENE-HBV towards dosing the first patient in the clinic,” added Dr. Murray Abramson, Senior Vice President, Head of Clinical Development of Precision BioSciences. “PBGENE-HBV is the first and only clinical stage approach to directly target and eliminate cccDNA, giving it the potential to achieve a functional cure. Next month, we plan to share additional information about our Phase 1 program, including the final preclinical safety package, with investigators and investors ahead of the upcoming AASLD meeting. With a clear regulatory pathway ahead of us, and our deep clinical expertise, we are focused on rapidly enrolling patients into the study and generating robust clinical data in patients with chronic hepatitis B who have for too long been unable to achieve meaningful functional cures.” Precision has submitted multiple global clinical trial applications and is on track to submit additional CTA and IND filings as part of its global Phase 1 regulatory strategy for PBGENE-HBV. The company will provide updates as it receives additional regulatory approvals to begin treating patients in those markets. The company plans to provide an update on the PBGENE-HBV program on November 15 th before the American Association for the Study of Liver Diseases (AASLD) Annual Meeting in November. Detailed information on how to join the webcast will be provided in the future. About Hepatitis B: Hepatitis B is a leading cause of morbidity in the US and death globally, with no curative options currently available for patients. In 2019, despite the availability of approved antiviral therapies, an estimated 300 million people globally and more than 1 million people in the US were estimated to have chronic hepatitis B infection. An estimated 15% to 40% of patients with HBV infections may develop complications, such as cirrhosis, liver failure, or liver cancer (hepatocellular carcinoma), which account for the majority of HBV-related deaths. Chronic hepatitis B infection is primarily driven by persistence of HBV cccDNA and integration of HBV DNA into the human genome in liver cells, the primary source of hepatitis B surface antigen (HBsAg) in late-stage disease. Current treatments for patients with HBV infection include agents that result in long-term viral suppression as indicated by reduction of circulating HBV DNA, but these therapies do not eradicate HBV cccDNA, rarely lead to functional cure, and require lifelong administration. About PBGENE-HBV: PBGENE-HBV is a potentially curative approach to treating patients with chronic HBV infection through a highly specific, novel therapeutic approach. PBGENE leverages the ARCUS ® platform and is designed to directly eliminate cccDNA and inactivate integrated HBV DNA with high specificity, potentially leading to functional cures. About Precision BioSciences, Inc. Precision BioSciences, Inc. is a clinical stage gene editing company dedicated to improving life (DTIL) with its novel and proprietary ARCUS® genome editing platform that differs from other technologies in the way it cuts, its smaller size, and its simpler structure. Key capabilities and differentiating characteristics may enable ARCUS nucleases to drive more intended, defined therapeutic outcomes. Using ARCUS, the Company’s pipeline is comprised of in vivo gene editing candidates designed to deliver lasting cures for the broadest range of genetic and infectious diseases where no adequate treatments exist. For more information about Precision BioSciences, please visit www.precisionbiosciences.com . The ARCUS ® platform is being used to develop in vivo gene editing therapies for sophisticated gene edits, including gene insertion (inserting DNA into gene to cause expression/add function), elimination (removing a genome e.g. viral DNA or mutant mitochondrial DNA), and excision (removing a large portion of a defective gene by delivering two ARCUS nucleases in a single AAV). SOURCE: Precision Biosciences

Precision Biosciences has received clearance from regulators in the Eastern European country of Moldova to begin a human trial of a gene editor for chronic hepatitis B, marking the first such test in the world. Precision’s ultimate goal is to use gene editing to functionally cure chronic hepatitis B, which to date is treatable but not curable. It’s a herculean task — a cure thus far has been elusive because the hepatitis B virus hides in a stable form in liver cells where it continues to make more copies of itself. “This is a disease indication where new therapies have really had a challenge, and patients have really been looking for better treatment options for a really long time,” Precision CEO Michael Amoroso said. People with chronic HBV can receive daily antiviral pills and interferon injections to treat the disease. Functional cure rates are around 2% on the antiviral pills alone and around 10% when combined with the injections but with significant side effects. The company’s Phase 1 trial will recruit from Moldova and up to four other countries. Amoroso declined to name those countries in an interview ahead of the announcement, though he confirmed Precision is pursuing an IND in the US. Precision uses its own gene editing platform it calls ARCUS, which was developed by North Carolina scientists who founded the company in 2006. Instead of CRISPR/Cas9, ARCUS uses an editing enzyme derived from algae. For chronic hepatitis B, Precision calls its experimental therapy PBGENE-HBV. The gene editor is delivered via a fatty acid envelope called a lipid nanoparticle, which accumulates in the liver. The gene editor is targeted to a sequence in HBV DNA that codes for the virus’ polymerase, which is an enzyme that helps make more copies of viral DNA. In doing so, Precision hopes gene editing can eliminate two forms of the hepatitis B viral DNA in liver cells that other approaches can’t get to: covalently closed circular DNA, or cccDNA, as well as HBV DNA that has integrated into the host DNA. cccDNA is a feature of certain viruses including HBV where its genetic code makes a stable ring inside the cell, and it also makes the virus very hard to cure. “The factory that makes replicating virus is that cccDNA,” Amoroso said. “So we’re not looking to cure symptoms, we’re looking to go at the root cause.” In May, Excision BioTherapeutics reported that its attempt to gene edit HIV failed. Like Precision, Excision’s goal is to use gene editing to excise hidden viruses from cells. However, there are some key differences — including that HIV is found in cells beyond the liver and Excision used viral envelopes called AAVs to try to reach those cells. Excision is likewise developing a gene editing therapy for HBV, for which it hopes to start clinical studies in 2026. Beam Therapeutics was also working on a gene editing approach to HBV but the company stopped work on the program in October last year as part of larger cost cuts and layoffs. It’s been a long road to this moment for Precision, which once developed CAR-T therapies before offloading that work to Imugene and in April saw Eli Lilly end a partnership on three programs. Gilead had signed on to Precision’s hepatitis B program in 2018, but axed the partnership in 2020, returning the rights to the gene editing company. In a May note to investors, BMO Capital Markets analyst Kostas Biliouris wrote that Precision “remains a ‘show me’ story wherein positive clinical data from the PBGENE-HBV program are needed to improve investor sentiment.”

The anti-CD38 mAb market is projected to experience substantial growth in the coming years owing to strong uptake of DARZALEX (along with DARZALEX FASPRO), the expected entry of subcutaneous formulation of SARCLISA in Multiple Myeloma. This growth is also driven by a rising number of cancer and autoimmune disorder diagnoses, as well as an increasing number of Anti-CD38 mAbs undergoing clinical trials and seeking approval. LAS VEGAS, Oct. 23, 2024 /PRNewswire/ -- DelveInsight's Anti-CD38 mAb Market Insights report includes a comprehensive understanding of current treatment practices, emerging anti-CD38 mAb, market share of individual therapies, and current and forecasted anti-CD38 mAb market size from 2020 to 2034, segmented into 7MM [the United States, the EU4 (Germany, France, Italy, and Spain), the United Kingdom, and Japan]. Key Takeaways from the Anti-CD38 mAb Market Report As per DelveInsight's analysis, the total market size of anti-CD38 mAb in the 7MM is expected to surge significantly by 2034. Multiple Myeloma is the only indication for which anti-CD38 therapies, Johnson&Johnson's (J&J) DARZALEX and Sanofi's SARCLISA have been approved until now. Around 50% of DARZALEX usage comes from second-line treatment in Multiple Myeloma. Additionally, in the frontline multiple myeloma clinical trials, DARZALEX has emerged triumphant, surpassing all expectations and solidifying its position as the gold standard of therapy. Its unparalleled effectiveness and exceptional safety profile have exceeded rivals' predictions and soon positioned DARZALEX to dominate the multiple myeloma market. The filing submission of SARCLISA subcutaneous in 3L R/R MM (IRAKLIA) is anticipated in 2025 and beyond. Somehow, SARCLISA is way behind DARZALEX in terms of market expansion, and DARZALEX has also got an early mover advantage of over 4 years. Multiple Myeloma is the leading indication, other emerging indications with commercial opportunity include Systemic Lupus Erythematosus (SLE), Chronic Kidney Disease (CKD), and IgA Nephropathy Leading emerging anti-CD38 mAb companies such as Takeda Pharmaceuticals, HI-Bio, Genmab, CASI Pharmaceuticals, and others are developing novel anti-CD38 mAb that can be available in the market in the coming years. Some of the key anti-CD38 mAb in the pipeline include Mezagitamab (TAK-079), Felzartamab, GEN3014, CID-103 , and others. In June 2024, data from the IMROZ Phase III study by Sanofi demonstrated that SARCLISA is the first anti-CD38 to significantly improve progression-free survival in combination with bortezomib, lenalidomide, and dexamethasone (VRd) for newly diagnosed transplant-ineligible multiple myeloma. In May 2024, Biogen and Human Immunology Biosciences (HI-Bio), announced the companies have entered into a definitive agreement under which Biogen has agreed to acquire HI-Bio for USD 1.15 billion upfront and up to USD 650 million in potential milestone payments. Discover which therapies are expected to grab the anti-CD38 mAb market share @ Anti-CD38 mAb Market Report Anti-CD38 mAb Market Dynamics The market for anti-CD38 mAbs has undergone significant growth and transformation in recent years, driven primarily by the increasing prevalence of multiple myeloma and the d emand for more effective treatment options. The market dynamics are further influenced by ongoing research into the broader application of anti-CD38 mAbs beyond multiple myeloma. There is growing interest in exploring their efficacy in other CD38-expressing malignancies, such as chronic lymphocytic leukemia and certain solid tumors. Additionally, research into combination therapies, where anti-CD38 mAbs are paired with immune checkpoint inhibitors, CAR-T cells, or other novel agents, is expanding the horizon for these treatments. Such advancements are likely to further propel the market, attracting substantial investment and fueling innovation. However, challenges such as biosimilar competition, pricing pressures, and the need for differentiation in a crowded market pose potential hurdles. The entrance of biosimilars could reduce costs but also threaten market share for existing products. Companies must navigate these challenges through strategic pricing, market access strategies, and continuous innovation to maintain their competitive edge. The anti-CD38 mAb market is poised for continued expansion, with a promising pipeline of new therapies and combinations on the horizon, making it a dynamic and evolving sector within oncology. Anti-CD38 mAb Treatment Market Monoclonal antibodies targeting CD38 are crucial in the treatment of newly diagnosed and refractory multiple myeloma. Currently, DARZALEX and SARCLISA are the two approved anti-CD38 therapies. SARCLISA is a prescription medication used to treat multiple myeloma in adults. It is administered alongside pomalidomide and dexamethasone for patients who have undergone at least two previous treatments, including lenalidomide and a proteasome inhibitor. Additionally, SARCLISA is used with carfilzomib and dexamethasone for patients who have received one to three prior therapies that were either ineffective or have stopped working. In March 2020, the US FDA approved SARCLISA in combination with pomalidomide and dexamethasone for multiple myeloma patients who had at least two prior therapies, including lenalidomide and a proteasome inhibitor. Later, in May 2020, the European Commission approved SARCLISA. By March 2021, the US FDA also approved SARCLISA with carfilzomib and dexamethasone for those with relapsed or refractory multiple myeloma who had received one to three previous treatments. DARZALEX is an innovative monoclonal antibody that the US FDA approved for treating multiple myeloma in patients with at least one prior treatment. It works by inducing tumor cell death through several mechanisms, including antibody-dependent cell-mediated cytotoxicity, complement-dependent cytotoxicity, and antibody-dependent cellular phagocytosis. In November 2015, the FDA granted DARZALEX accelerated approval as a monotherapy for multiple myeloma patients who had undergone at least three prior treatments. By November 2016, it was also approved for use in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for patients who had received at least one prior therapy. From 2015 to 2021, DARZALEX gained further approvals for use in various drug combinations. Their effectiveness in managing multiple myeloma and plasma cell disorders has been confirmed by numerous Phase III clinical trials. Moreover, CD38-targeted therapies are being explored for other conditions such as primary immune thrombocytopenia, IgA nephropathy, antibody-mediated transplant rejection, lupus nephritis, and various hematologic cancers. Learn more about the FDA-approved anti-CD38 mAb @ Anti-CD38 mAb Drugs Key Emerging Anti-CD38 mAb and Companies Several key players, including Takeda Pharmaceuticals, HI-Bio, CASI Pharmaceuticals, and others, are involved in developing drugs for Anti-CD38 mAb for various indications such as multiple myeloma, myasthenia gravis, and others. Mezagitamab is a fully human IgG1 monoclonal antibody that targets CD38 and is being developed by Takeda for the treatment of multiple myeloma, myasthenia gravis, and primary immune thrombocytopenia. On March 14, 2024, the FDA granted Fast Track designation and Orphan Drug status to mezagitamab for idiopathic thrombocytopenic purpura (ITP). Takeda also revealed plans to begin a global Phase III trial for mezagitamab in ITP later in 2024. The drug is currently in Phase II of clinical development. HI-Bio's leading candidate, felzartamab, is a fully human anti-CD38 monoclonal antibody. Clinical studies have demonstrated its ability to selectively target and deplete CD38+ cells, including plasma cells and NK cells, potentially enabling broader therapeutic applications and enhanced clinical outcomes across various immune-mediated diseases. Felzartamab has been granted Breakthrough Therapy and Orphan Drug Designations by the FDA for primary membranous nephropathy and also received Orphan Drug Designation for treating antibody-mediated kidney transplant recipients. Phase II trials have been completed for primary membranous nephropathy and antibody-mediated transplant rejection, with ongoing studies in IgA nephropathy. HI-Bio intends to progress each of these indications to Phase III. The anticipated launch of these emerging therapies are poised to transform the anti-CD38 mAb market landscape in the coming years. As these cutting-edge therapies continue to mature and gain regulatory approval, they are expected to reshape the anti-CD38 mAb market landscape, offering new standards of care and unlocking opportunities for medical innovation and economic growth. To know more about anti-CD38 mAb clinical trials, visit @ Anti-CD38 mAb Treatment Drugs Anti-CD38 mAb Overview Anti-CD38 monoclonal antibodies (mAbs) are a class of therapeutic agents that target CD38, a surface protein widely expressed on plasma cells, including malignant ones in multiple myeloma. By binding to CD38, these mAbs can induce direct cytotoxicity, promote antibody-dependent cellular cytotoxicity (ADCC), and facilitate complement-dependent cytotoxicity (CDC) to destroy the targeted cells. Beyond their role in multiple myeloma, anti-CD38 mAbs are being explored for their potential in treating other hematologic malignancies and autoimmune diseases. CD38 is not only a marker for plasma cells but also involved in processes like calcium signaling and NAD+ metabolism, which are crucial for cell survival and proliferation. By targeting CD38, these antibodies can modulate the immune microenvironment, making them a promising tool for both oncology and immunology. The ongoing research is focused on optimizing their efficacy, managing resistance, and exploring their use in combination with other immunotherapies to enhance patient outcomes. Anti-CD38 mAb Epidemiology Segmentation Epidemiology assessed for multiple myeloma showed that the United States, in 2023, accounted for 36,800 incident cases of multiple myeloma. The anti-CD38 mAb market report proffers epidemiological analysis for the study period 2020–2034 in the 7MM segmented into: Total Incident Cases of Selected Indication for Anti-CD38 mAb Total Eligible Patient Pool for Anti-CD38 mAb in Selected Indication Total Treatable Cases of Selected Indications for Anti-CD38 mAb Scope of the Anti-CD38 mAb Market Report Anti-CD38 mAb Therapeutic Assessment: Anti-CD38 mAb current marketed and emerging therapies Anti-CD38 mAb Market Dynamics: Conjoint Analysis of Emerging Anti-CD38 mAb Drugs Competitive Intelligence Analysis: SWOT analysis and Market entry strategies Unmet Needs, KOL's views, Analyst's views, Anti-CD38 mAb Market Access and Reimbursement Discover more about anti-CD38 mAb in development @ Anti-CD38 mAb Clinical Trials Table of Contents Related Reports Multiple Myeloma Market Multiple Myeloma Market Insight, Epidemiology and Market Forecast – 2034 report deliver an in-depth understanding of the disease, historical and forecasted epidemiology, as well as the market trends, market drivers, market barriers, and key multiple myeloma companies, including Johnson & Johnson (Janssen), Pfizer, AbbVie and Roche (Genentech), Regeneron Pharmaceuticals, Bristol-Myers Squibb, Celgene, Roche (Genentech), Arcellx, Novartis, Regeneron Pharmaceuticals, BeiGene, CARsgen Therapeutics, Cartesian Therapeutics, C4 Therapeutics, Heidelberg Pharma, Bristol-Myers Squibb, RAPA Therapeutics, AbbVie (TeneoOne), Takeda , among others. Multiple Myeloma Pipeline Multiple Myeloma Pipeline Insight – 2024 report provides comprehensive insights about the pipeline landscape, pipeline drug profiles, including clinical and non-clinical stage products, and the key multiple myeloma companies, including Janssen, Pharmacyclics, Novartis, Incyte Corporation, Gracell Biotechnology, SpringWorks Therapeutics, Sana Biotechnology, Cytovia Therapeutics, Pfizer, MorphoSys, Biokine Therapeutics, Arcellx, Rapa Therapeutics, iTeos Therapeutics, Sorrento Therapeutics, CARsgen, Ascentage Pharma, Cartesian Therapeutics, Bristol-Myers Squibb, Juno Therapeutics, Nanjing IASO Biotherapeutics, Arch Oncology, Oncoceutics, TeneoBio, Nerviano Medical Sciences, among others. Relapse/Refractory Multiple Myeloma Market Relapse/Refractory Multiple Myeloma Market Insights, Epidemiology, and Market Forecast – 2032 report delivers an in-depth understanding of the disease, historical and forecasted epidemiology, as well as the market trends, market drivers, market barriers, and key R/R multiple myeloma companies, including NexImmune, Amgen, AbbVie, Allogene Therapeutics, Precision Biosciences, Takeda Oncology, ORIC Pharmaceuticals, Ionis Pharmaceuticals, Cellectis S.A., YZY Biopharma, Janssen Research & Development, Bristol Myers Squibb, Lava Therapeutics, Prelude Therapeutics, among others. Relapse/Refractory Multiple Myeloma Pipeline Relapse/Refractory Multiple Myeloma Pipeline Insight – 2024 report provides comprehensive insights about the pipeline landscape, pipeline drug profiles, including clinical and non-clinical stage products, and the key R/R multiple myeloma companies, including Bristol-Myers Squibb, I-MAB Biopharma, Pfizer, Arcellx, Gilead Sciences, Novartis, Array Biopharma, Hrain Biotechnology Co., Ltd., Cartesian Therapeutics, Xencor, Takeda, Sorrento Therapeutics, Heidelberg Pharma AG, Ichnos Sciences, Allogene Therapeutics, Harpoon Therapeutics, Cellectis, Poseida Therapeutics, Regeneron Pharmaceuticals, ONK Therapeutics, TeneoOne, iTeos Therapeutics, Oricell Therapeutics, Anaveon AG, Luminary Therapeutics, Seagen Inc., Trillium Therapeutics Inc., Virtuoso BINco, Inc., Seagen Inc., Trillium Therapeutics Inc., among others. About DelveInsight DelveInsight is a leading Business Consultant and Market Research firm focused exclusively on life sciences. 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