Precision BioSciences Highlights Preclinical Data and Outlines Design of First-in-Human Clinical Trial for PBGENE-HBV for Treatment of Chronic Hepatitis B
Precision BioSciences (DTIL) has presented preclinical data for PBGENE-HBV, its gene editing therapy for chronic hepatitis B, and outlined its Phase 1 ELIMINATE-B trial design. The preclinical data showed 99% viral DNA editing in non-human primates, effective hepatocyte distribution, and sustained declines in viral biomarkers. The ELIMINATE-B trial will evaluate up to 45 HBeAg-negative patients across five countries, with data expected throughout 2025. The company has received clearance to begin trials in Moldova, with additional regulatory applications pending. The therapy targets approximately 300 million people globally affected by chronic hepatitis B, addressing an unmet need in a multi-billion-dollar market where current treatments achieve functional cure in less than 3% of patients.
Precision BioSciences (DTIL) ha presentato dati preclinici per PBGENE-HBV, la sua terapia di editing genico per l'epatite B cronica, e ha delineato il design del trial di Fase 1 ELIMINATE-B. I dati preclinici hanno mostrato un editing del DNA virale del 99% in primati non umani, una distribuzione efficace degli epatociti e diminuzioni sostenute nei biomarcatori virali. Il trial ELIMINATE-B valuterà fino a 45 pazienti HBeAg-negativi in cinque paesi, con dati attesi per tutto il 2025. La società ha ricevuto l'autorizzazione per iniziare i trial in Moldavia, con ulteriori domande regolatorie in sospeso. La terapia si rivolge a circa 300 milioni di persone in tutto il mondo affette da epatite B cronica, rispondendo a un'esigenza non soddisfatta in un mercato da miliardi di dollari, dove i trattamenti attuali raggiungono una cura funzionale in meno del 3% dei pazienti.
Precision BioSciences (DTIL) ha presentado datos preclínicos para PBGENE-HBV, su terapia de edición genética para la hepatitis B crónica, y ha delineado el diseño de su ensayo de Fase 1 ELIMINATE-B. Los datos preclínicos mostraron un 99% de edición de ADN viral en primates no humanos, distribución efectiva de hepatocitos y disminuciones sostenidas en los biomarcadores virales. El ensayo ELIMINATE-B evaluará hasta 45 pacientes HBeAg-negativos en cinco países, con datos esperados a lo largo de 2025. La compañía ha recibido la autorización para comenzar ensayos en Moldavia, con solicitudes regulatorias adicionales pendientes. La terapia se dirige a aproximadamente 300 millones de personas en todo el mundo afectadas por la hepatitis B crónica, abordando una necesidad no satisfecha en un mercado de miles de millones de dólares, donde los tratamientos actuales logran una cura funcional en menos del 3% de los pacientes.
Precision BioSciences (DTIL)는 만성 B형 간염을 위한 유전자 편집 치료제 PBGENE-HBV의 전임상 데이터를 발표하고 1상 ELIMINATE-B 시험 설계를 개요했습니다. 전임상 데이터는 비인간 영장류에서 99%의 바이러스 DNA 편집, 효과적인 간세포 분포 및 바이러스 바이오마커의 지속적인 감소를 보여주었습니다. ELIMINATE-B 시험은 5개국에서 최대 45명의 HBeAg 음성 환자를 평가할 예정이며, 데이터는 2025년 내내 예상됩니다. 이 회사는 몰도바에서 시험을 시작할 수 있는 승인을 받았으며, 추가 규제 신청도 대기 중입니다. 이 치료법은 만성 B형 간염에 영향을 받는 전 세계 약 3억 명을 대상으로 하여, 환자의 3% 미만이 기능적 치료를 달성하는 수십억 달러 규모의 시장에서 충족되지 않은 필요를 다룹니다.
Precision BioSciences (DTIL) a présenté des données précliniques pour PBGENE-HBV, sa thérapie de modification génétique pour l'hépatite B chronique, et a décrit le design de son essai de Phase 1 ELIMINATE-B. Les données précliniques ont montré un editing de l'ADN viral à 99% chez des primates non humains, une distribution efficace des hépatocytes et des diminutions soutenues des biomarqueurs viraux. L'essai ELIMINATE-B évaluera jusqu'à 45 patients HBeAg-négatifs dans cinq pays, avec des données attendues tout au long de 2025. L'entreprise a reçu l'autorisation de commencer des essais en Moldavie, avec d'autres demandes réglementaires en attente. La thérapie cible environ 300 millions de personnes dans le monde touchées par l'hépatite B chronique, répondant à un besoin non satisfait sur un marché de plusieurs milliards de dollars, où les traitements actuels atteignent une guérison fonctionnelle chez moins de 3% des patients.
Precision BioSciences (DTIL) hat präklinische Daten zu PBGENE-HBV, seiner Gentherapie gegen chronische Hepatitis B, präsentiert und das Design der Phase 1-Studie ELIMINATE-B skizziert. Die präklinischen Daten zeigten eine 99%ige Bearbeitung der viralen DNA bei nicht-menschlichen Primaten, eine effektive Verteilung von Hepatozyten und nachhaltige Rückgänge bei viralen Biomarkern. Die ELIMINATE-B-Studie wird bis zu 45 HBeAg-negativen Patienten in fünf Ländern bewerten, wobei Daten bis Ende 2025 erwartet werden. Das Unternehmen hat die Genehmigung erhalten, Studien in Moldawien zu beginnen, während weitere regulatorische Anträge ausstehen. Die Therapie richtet sich an etwa 300 Millionen Menschen weltweit, die von chronischer Hepatitis B betroffen sind, und spricht ein unzureichend gedecktes Bedürfnis auf einem Milliardenmarkt an, in dem die derzeitigen Behandlungen bei weniger als 3% der Patienten eine funktionale Heilung erreichen.
- Preclinical data showed 99% viral DNA editing efficacy in non-human primates
- Received first clinical trial approval in Moldova
- Addresses large market opportunity of 300 million patients globally
- Targets multi-billion dollar market with over 5 million patients on current treatments
- U.S. IND approval not expected until 2025
- Multiple regulatory approvals still pending
- Will require multiple dose administrations per patient
Insights
The advancement of PBGENE-HBV into clinical trials represents a significant milestone in chronic hepatitis B treatment. The preclinical data shows 99% viral DNA editing efficacy in non-human primates and demonstrates elimination of cccDNA, addressing both key drivers of hepatitis B infection. With 300 million people affected globally and current treatments achieving only
The ELIMINATE-B trial design is robust, targeting HBeAg-negative patients who represent
This development positions Precision BioSciences to potentially capture a significant share of the multi-billion dollar hepatitis B market, which currently serves 5 million patients worldwide. The company's ARCUS platform demonstrates competitive advantages in gene editing specificity and efficiency. The global trial strategy, starting with Moldova and expanding to five countries, shows a measured approach to clinical development while maintaining cost efficiency.
The focus on HBeAg-negative patients, representing the majority of cases, indicates smart market positioning. If successful, PBGENE-HBV could establish a new standard of care in hepatitis B treatment, transitioning from chronic management to potential functional cures. This represents a substantial market opportunity, particularly given the high progression rate to serious liver conditions.
– PBGENE-HBV preclinical data reinforce safety profile and potential to deliver a functional cure for chronic hepatitis B, supporting advancement into first-in-human clinical study –
– Phase 1 dose escalation and expansion trial, ELIMINATE-B, designed to assess safety and efficacy measured by durable reduction of key viral biomarkers –
– Global study recruiting patients following clearance of first clinical trial application (CTA), with additional CTAs pending approval;
– Investor event today, November 15, 10:00 a.m. EST / 7:00 a.m. PST, to feature presentations from company management and key opinion leader perspectives on PBGENE-HBV –
“We are excited to share the preclinical data supporting PBGENE-HBV alongside the design of our Phase 1 trial, ELIMINATE-B, which will be the first clinical study of an in vivo gene editing program in chronic hepatitis B,” said Michael Amoroso, Chief Executive Officer, Precision BioSciences. “Chronic hepatitis B affects approximately 300 million people globally and represents a multi-billion-dollar market with chronic treatments currently serving more than 5 million patients worldwide. However, most available treatments for chronic hepatitis B target downstream aspects of the viral lifecycle, leaving the root of disease intact. Consequently, less than
“Our preclinical results reflect the robust data package submitted to regulators in support of our global Phase 1 trial and underscore our conviction in PBGENE-HBV, which has so far demonstrated compelling safety and selectivity, highly efficient editing, and confirmation of its mechanism to eliminate cccDNA and viral DNA integrated into hepatocytes,” said Murray Abramson, M.D., M.P.H., Head of Clinical Development, Precision BioSciences. “Importantly, the ELIMINATE-B study will evaluate patients who are controlled but not cured by nucleoside analogues. We believe ELIMINATE-B will highlight the differentiated mechanism of PBGENE-HBV. By simultaneously targeting the two distinct drivers of disease – cccDNA and viral DNA integrated into hepatocytes – PBGENE-HBV has the potential to deliver a much-needed functional cure for people living with chronic hepatitis B.”
Mr. Amoroso added, “With regulatory authorization in place and global sites coming online, we are excited to begin dosing patients with PBGENE-HBV and look forward to sharing clinical data as it matures in 2025.”
PBGENE-HBV Preclinical Data Highlights:
Today, Precision will present preclinical data generated to date, which support the progression of PBGENE-HBV into a first-in-human clinical trial. The Company will share robust safety, tolerability, and efficacy signals observed through an array of preclinical models. Key highlights are as follows:
Safety and Tolerability:
- Comprehensive off-target analysis demonstrated a high degree of specificity for PBGENE-HBV, with no increased risks of translocations or integrations in HBV-infected human liver cells;
- PBGENE-HBV was well tolerated over multiple administrations in mice and non-human primates (NHPs), with rapid clearance after each dose administration, transient transaminase elevations which resolved rapidly, and non-adverse changes in blood parameters;
- PBGENE-HBV does not distribute to germ cells, as evidenced by NHP studies; and
- PBGENE-HBV’s high-quality mRNA and optimized LNP formulation contributed to a compelling safety profile.
Efficacy:
- PBGENE-HBV effectively distributed to all hepatocytes in the liver;
-
PBGENE-HBV demonstrated
99% viral DNA editing in NHPs; - Confirmed PBGENE-HBV’s dual mechanism with elimination of cccDNA observed in primary human hepatocyte, mouse, and NHP models and inactivation of integrated HBV DNA observed in transgenic mouse models and HBV cell lines; and
- Observed sustained declines in key viral biomarkers, HBV DNA and hepatitis B surface antigen (HBsAg), indicative of a functional cure in transgenic mouse models following administration of PBGENE-HBV and nucleoside analogue withdrawal.
Based on these data, Precision has submitted clinical trial applications to authorities in multiple geographies and has so far received clearance to initiate its Phase 1 study in
ELIMINATE-B Phase 1 Trial Design and Overview:
ELIMINATE-B is a global, multi-site, Phase 1 clinical trial, which will evaluate up to 45 HBV patients that are hepatitis B e antigen (HBeAg)-negative and virologically suppressed on nucleos(t)ide analogues (NUCs). Since greater than
ELIMINATE-B is open and currently screening and accruing patients, and Precision expects to report data from the study as it matures throughout 2025.
Further details on the trial can be found in the event slides posted on Precision’s website in the Investors section under Events & Presentations at investor.precisionbiosciences.com and on clinicaltrials.gov identifier NCT06680232.
Investor Event Webcast Information:
Precision’s investor event will include presentations by management on the preclinical data for PBGENE-HBV and the design of ELIMINATE-B. Panel discussions will feature leading hepatitis experts and Precision Scientific Advisory Board members on the market opportunity in HBV, and investigators on their clinical experience treating HBV and the potential for PBGENE-HBV to address this unmet need.
The event will be webcast live on Friday, November 15, 2024, at 10:00 a.m. EST / 7:00 a.m. PST. To access the presentation and webcast, please use the following link or go to Precision’s website in the Investors section under Events & Presentations at investor.precisionbiosciences.com. An archived replay of the webcast will be available for approximately 30 days following the event.
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. Precision BioSciences is currently enrolling patients in the ELIMINATE-B Phase 1 trial evaluating PBGENE-HBV in patients with chronic hepatitis B. For more information on the ELIMINATE-B trial, please visit clinicaltrials.gov identifier NCT06680232. 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 a 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).
Forward Looking Statements
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements contained in this press release that do not relate to matters of historical fact should be considered forward-looking statements, including, without limitation, statements regarding the clinical development and expected safety, efficacy and benefit of our product candidates (including PBGENE-HBV); the unique design of PBGENE-HBV to eliminate cccDNA and inactivate integrated HBV DNA with high specificity, potentially leading to functional cures; the expected timing of regulatory processes (including filings such as IND’s and CTA’s and studies for PBGENE-HBV and the acceptance of these filings by regulatory agencies); the suitability of PBGENE-HBV for the treatment of hepatitis and the targeting of the root cause of the disease; the robust safety, tolerability and efficacy signals observed through preclinical evaluation in non-human primates (NHPs), transgenic and episomal mouse models, human cell models of HBV and primary human hepatocytes; the translatability of preclinical models to human clinical trials; the key advantages of ARCUS and its key capabilities and differentiating characteristics ; expectations about operational initiatives, strategies, and further development of PBGENE-HBV; expectations about achievement of key milestones; and anticipated timing of patient dosing and clinical data. In some cases, you can identify forward-looking statements by terms such as “aim,” “anticipate,” “approach,” “believe,” “contemplate,” “could,” “design”, “designed,” “estimate,” “expect,” “goal,” “intend,” “look,” “may,” “mission,” “plan,” “possible,” “potential,” “predict,” “project,” “pursue,” “should,” “strive,” “target,” “will,” “would,” or the negative thereof and similar words and expressions.
Forward-looking statements are based on management’s current expectations, beliefs and assumptions and on information currently available to us. These statements are neither promises nor guarantees, and involve a number of known and unknown risks, uncertainties and assumptions, and actual results may differ materially from those expressed or implied in the forward-looking statements due to various important factors, including, but not limited to, our ability to become profitable; our ability to procure sufficient funding to advance our programs; risks associated with our capital requirements, anticipated cash runway, requirements under our current debt instruments and effects of restrictions thereunder, including our ability to raise additional capital due to market conditions and/or our market capitalization; our operating expenses and our ability to predict what those expenses will be; our limited operating history; the progression and success of our programs and product candidates in which we expend our resources; our limited ability or inability to assess the safety and efficacy of our product candidates; the risk that other genome-editing technologies may provide significant advantages over our ARCUS technology; our dependence on our ARCUS technology; the initiation, cost, timing, progress, achievement of milestones and results of research and development activities and preclinical and clinical studies, including clinical trial and investigational new drug applications; public perception about genome editing technology and its applications; competition in the genome editing, biopharmaceutical, and biotechnology fields; our or our collaborators’ or other licensees’ ability to identify, develop and commercialize product candidates; pending and potential product liability lawsuits and penalties against us or our collaborators or other licensees related to our technology and our product candidates; the
All forward-looking statements speak only as of the date of this press release and, except as required by applicable law, we have no obligation to update or revise any forward-looking statements contained herein, whether as a result of any new information, future events, changed circumstances or otherwise.
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Investor and Media Contact:
Naresh Tanna
Vice President of Investor Relations
naresh.tanna@precisionbiosciences.com
Source: Precision BioSciences
FAQ
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