A Phase 2b, Multi-centre, Randomized, Partially Placebo-controlled, Double-blind Study to Investigate the Safety and Efficacy of Sequential Therapy With Daplusiran/Tomligisiran Followed by Bepirovirsen in Participants With Chronic Hepatitis B Virus on Background Nucleos(t)Ide Analogue Therapy (B-United)

The study is intended to evaluate the efficacy and safety of 2 different doses of DAP/TOM followed by bepirovirsen in participants living with CHB on standard of care nucleos(t)ide analogue (NA) therapy. The study also aims to identify an optimal dose of DAP/TOM for sequenced therapy with bepirovirsen for further clinical development and to assess the contribution of DAP/TOM to the sequential regimen.

Start Date11 Nov 2024

Sponsor / Collaborator

GSK Plc

NCT05275023

/ CompletedPhase 2

A Phase 2 Open-label Trial to Evaluate Safety, Efficacy, Tolerability, and Pharmacodynamics of a Combination of JNJ-73763989, Nucleos(t)Ide Analogs, and a PD-1 Inhibitor in Chronic Hepatitis B Patients

The purpose of this study is to evaluate efficacy of the study intervention, based on hepatitis B surface antigen (HBsAg) levels at follow-up (FU) Week 24.

Start Date30 Jun 2022

Sponsor / Collaborator

Janssen Research & Development LLC

CTR20210504

/ TerminatedPhase 2

一项在乙型和丁型肝炎病毒合并感染的受试者中评估JNJ-73763989联合核苷（酸）类似物的疗效、安全性和药代动力学的Ⅱ期、多中心、随机、双盲、安慰剂对照、延时活性治疗研究

[Translation] A Phase II, multicenter, randomized, double-blind, placebo-controlled, extended-active treatment study to evaluate the efficacy, safety, and pharmacokinetics of JNJ-73763989 in combination with nucleoside (acid) analogs in subjects co-infected with hepatitis B and D viruses

评价JNJ-3989+NA方案与NA单药相比，对于HDV的治疗期间疗效。

[Translation]

To evaluate the efficacy of JNJ-3989+NA regimen compared with NA alone for the treatment period of HDV.

Start Date22 Mar 2022

Sponsor / Collaborator

Catalent CTS LLC

[+6]

100 Clinical Results associated with Daplusiran/Tomligisiran

100 Translational Medicine associated with Daplusiran/Tomligisiran

100 Patents (Medical) associated with Daplusiran/Tomligisiran

Literatures (Medical) associated with Daplusiran/Tomligisiran

01 Mar 2025·GUT

Long-term hepatitis B surface antigen response after finite treatment of ARC-520 or JNJ-3989

Article

Author: Wooddell, Christine I ; Mak, Lung Yi ; Lenz, Oliver ; Yuen, Man-Fung ; Biermer, Michael ; Hamilton, James ; Seto, Wai-Kay ; Mao, Xianhua ; Schluep, Thomas ; Davis, Heather L

Background and aims:

RNA interference has been extensively explored in patients with chronic hepatitis B (CHB) infection. We aimed to characterise the long-term efficacy of small interfering RNA (siRNA) on hepatitis B surface antigen (HBsAg) suppression.

Methods:

We prospectively followed up participants with CHB who received siRNA, either ARC-520 or JNJ-73763989 (JNJ-3989), in combination with nucleoside analogue (NUC) in our centre. Participants enrolled included 15 receiving 4 monthly injections of ARC-520, 38 receiving 3 injections of JNJ-3989 at 1, 2 or 4 weekly intervals and 5 receiving placebo in previous clinical trials. Serial blood sampling was performed according to the original protocols and on completion every 24 weeks until last follow-up (LFU) with mean duration of 52.5 months.

Results:

Among the 53 NUC+siRNA-treated participants (mean age 46.8, baseline HBsAg 3.08 log, 83% previously on NUC, 34% hepatitis B e antigen+), the proportion of patients achieving HBsAg seroclearance or <100 IU/mL at LFU was 1.9% and 32.1%, respectively, compared with 0% and 0% for placebo. Among siRNA-recipients, 48.5% and 5.0% of those with HBsAg <100 IU/mL and >100 IU/mL at nadir or ≤24 weeks from last dose could maintain or achieve HBsAg <100 IU/mL at LFU, respectively. Compared with placebo recipients, siRNA-recipients demonstrated faster overall annual decline of HBsAg (0.08 vs 0.21 log IU/mL/year) contributed predominantly by changes in the first year. Age was negatively correlated with HBsAg reduction at LFU (r=−0.427, p=0.001).

Conclusion:

Short-duration siRNA treatment suppressed HBsAg expression with a prolonged effect for up to 6 years in some participants.

01 Sep 2024·Journal of hepatology

JNJ-73763989 and bersacapavir treatment in nucleos(t)ide analogue-suppressed patients with chronic hepatitis B: REEF-2

Article

Author: van Bömmel, Florian ; Lonjon-Domanec, Isabelle ; Jezorwski, John ; Beumont, Maria ; Lenz, Oliver ; Biermer, Michael ; Buti, Maria ; Mayer, Cristiana ; Kalmeijer, Ronald ; Lampertico, Pietro ; Verbinnen, Thierry ; Vanwolleghem, Thomas ; Agarwal, Kosh ; Kakuda, Thomas N ; Bourliere, Marc ; Muenz, Daniel ; Janczewska, Ewa

BACKGROUND & AIMS:

Functional cure for chronic hepatitis B (CHB) requires finite treatment. Two agents under investigation with the goal of achieving functional cure are the small-interfering RNA JNJ-73763989 (JNJ-3989) and the capsid assembly modulator JNJ-56136379 (JNJ-6379; bersacapavir).

METHODS:

REEF-2, a phase IIb, double-blind, placebo-controlled, randomized study, enrolled 130 nucleos(t)ide analogue (NA)-suppressed hepatitis B e-antigen (HBeAg)-negative patients with CHB who received JNJ-3989 (200 mg subcutaneously every 4 weeks) + JNJ-6379 (250 mg oral daily) + NA (oral daily; active arm) or placebos for JNJ-3989 and JNJ-6379 +active NA (control arm) for 48 weeks followed by 48 weeks off-treatment follow-up.

RESULTS:

At follow-up Week 24, no patients achieved the primary endpoint of functional cure (off-treatment hepatitis B surface antigen [HBsAg] seroclearance). No patients achieved functional cure at follow-up Week 48. There was a pronounced on-treatment reduction in mean HBsAg from baseline at Week 48 in the active arm vs. no decline in the control arm (1.89 vs. 0.06 log₁₀ IU/ml; p = 0.001). At follow-up Week 48, reductions from baseline were >1 log₁₀ IU/ml in 81.5% vs. 12.5% of patients in the active and control arms, respectively, and 38/81 (46.9%) patients in the active arm achieved HBsAg <100 IU/ml vs. 6/40 (15.0%) patients in the control arm. Off-treatment HBV DNA relapse and alanine aminotransferase increases were less frequent in the active arm with 7/77 (9.1%) and 11/41 (26.8%) patients in the active and control arms, respectively, restarting NAs during follow-up.

CONCLUSIONS:

Finite 48-week treatment with JNJ-3989 + JNJ-6379 + NA resulted in fewer and less severe post-treatment HBV DNA increases and alanine aminotransferase flares, and a higher proportion of patients with off-treatment HBV DNA suppression, with or without HBsAg suppression, but did not result in functional cure.

IMPACT AND IMPLICATIONS:

Achieving a functional cure from chronic hepatitis B (CHB) with finite treatments is a major unmet medical need. The current study assessed the rate of functional cure and clinical outcome after controlled nucleos(t)ide analogue (NA) withdrawal in patients with low levels of HBsAg induced by 48 weeks of treatment with the small-interfering RNA JNJ-3989 and the capsid assembly modulator JNJ-6379 plus NA vs. patients who only received NA treatment. Though functional cure was not achieved by any patient in either arm, the 48-week treatment regimen of JNJ-3989, JNJ-6379, and NA did result in more patients achieving pronounced reductions in HBsAg, with clinically meaningful reductions maintained for up to 48 weeks off all treatments, as well as fewer off-treatment HBV DNA increases and alanine aminotransferase flares. These findings provide valuable insights for future studies investigating potential finite treatment options, while the reported efficacy and safety outcomes may be of interest to healthcare providers making treatment decisions for patients with NA-suppressed HBeAg-negative CHB.

CLINICALTRIALS:

GOV IDENTIFIER:

NCT04129554.

01 Sep 2023·The lancet. Gastroenterology & hepatology

Efficacy and safety of the siRNA JNJ-73763989 and the capsid assembly modulator JNJ-56136379 (bersacapavir) with nucleos(t)ide analogues for the treatment of chronic hepatitis B virus infection (REEF-1): a multicentre, double-blind, active-controlled, randomised, phase 2b trial

Article

BACKGROUND:

JNJ-73763989 (JNJ-3989), a small interfering RNA, targets all hepatitis B virus (HBV) RNAs, reducing all HBV proteins. JNJ-56136379 (JNJ-6379; also known as bersacapavir), a capsid assembly modulator, inhibits HBV replication. We aimed to evaluate the efficacy (ie, antiviral activity) and safety of these therapeutics in combination with nucleos(t)ide analogues in patients with chronic hepatitis B.

METHODS:

The REEF-1 multicentre, double-blind, active-controlled, randomised, phase 2b study was done at 108 hospitals or outpatient centres across 19 countries in Asia, Europe, and North and South America. We included patients aged 18-65 years with chronic hepatitis B (defined as HBsAg positivity at screening and at least 6 months before screening or alternative markers of chronicity [eg, HBV DNA]), including those not currently treated, virologically suppressed, HBeAg positive, and HBeAg negative. Patients were randomly assigned (1:1:2:2:2:2) via permuted block randomisation according to a computer-generated schedule to receive oral nucleos(t)ide analogues once per day plus placebo (control group); oral JNJ-6379 250 mg daily plus nucleos(t)ide analogues (JNJ-6379 dual group); nucleos(t)ide analogues plus subcutaneously injected JNJ-3989 at doses of 40 mg (JNJ-3989 dual 40 mg group), 100 mg (JNJ-3989 dual 100 mg group), or 200 mg (JNJ-3989 dual 200 mg group) every 4 weeks; or JNJ-6379 250 mg plus JNJ-3989 100 mg every 4 weeks plus nucleos(t)ide analogues (triple group) for 48 weeks followed by a follow-up phase. An interactive web response system provided concealed treatment allocation, and investigators remained masked to the intervention groups until the primary analysis at week 48. The primary endpoint was the proportion of patients meeting predefined nucleos(t)ide analogue-stopping criteria (alanine aminotransferase <3 × upper limit of normal, HBV DNA below the lower limit of quantitation, HBeAg negative, and HBsAg <10 IU/mL) at week 48. All patients who received at least one dose of study drug were included in the analysis population used for primary efficacy assessment, excluding those who withdrew because of COVID-19-related reasons, withdrew before week 44, or had no efficacy data (ie, the modified intention-to-treat population). Safety was assessed in all participants who received at least one dose of study drugs. This trial is registered with ClinicalTrials.gov, NCT03982186. The study has been completed.

FINDINGS:

Between Aug 1, 2019, and April 26, 2022, 470 patients (310 [66%] male and 244 [52%] White) were randomly assigned: 45 to the control group, 48 to the JNJ-6379 dual group, 93 to the JNJ-3989 dual 40 mg group, 93 to the JNJ-3989 dual 100 mg group, 96 to the JNJ-3989 dual 200 mg group, and 95 to the triple group. At week 48, five (5%; 90% CI 2-11) of 91 patients in the JNJ-3989 dual 40 mg group, 15 (16%; 10-24) of 92 in the JNJ-3989 dual 100 mg group, 18 (19%; 13-27) of 94 in the JNJ-3989 dual 200 mg group, eight (9%; 4-15) of 94 in the triple group, and one (2%; 0-10) of 45 in the control group met nucleos(t)ide analogue stopping criteria. No patients in the JNJ-6379 dual group met stopping criteria. 38 (81%) patients who met nucleos(t)ide analogue-stopping criteria at week 48 were virologically suppressed and HBeAg negative at baseline. Ten (2%) of 470 patients had serious adverse events during the treatment phase, and two patients (one each from the JNJ-3989 dual 200 mg group [exercise-related rhabdomyolysis] and the triple group [increase in ALT or AST]) had serious adverse events related to study treatment. During follow-up, 12 (3%) of 460 patients had a serious adverse event; one (<1%), a gastric ulcer, was considered to be related to nucleos(t)ide analogues and occurred in a patient from the JNJ-3989 dual 200 mg group. 29 (6%) of 460 patients in the treatment phase and in ten (2%) of 460 patients in the follow-up phase had grade 3 or 4 adverse events. Five (1%) of 470 patients discontinued treatment due to adverse events, and there were no deaths.

INTERPRETATION:

Although treatment with JNJ-3989 led to a dose-dependent response for meeting nucleos(t)ide analogue-stopping criteria, it rarely led to HBsAg seroclearance. However, most patients treated with JNJ-3989 had clinically meaningful reductions in HBsAg that might contribute to a liver environment conducive to better immune control and, in turn, might improve the response to immune-modulating therapies.

FUNDING:

Janssen Research and Development.

News (Medical) associated with Daplusiran/Tomligisiran

05 Feb 2025

·www.fiercebiotech.com

GSK drops one potential \'functional cure\' for hep B as it goes all-in on bepirovirsen

Hopes for GSK3528869 appeared to be dashed in December when GSK terminated a phase 1/2 chronic hepatitis B study.\n GSK is prioritizing development of its hepatitis B treatment bepirovirsen as the pharma ends work on another potential functional cure for the infectious disease.On a media call Wednesday morning to discuss her company\'s fourth-quarter and full-year earnings, CEO Emma Walmsley said that when it came to the British pharma’s infectious disease pipeline, “we\'re prioritizing development of bepirovirsen, our potential functional cure for hepatitis B.”The pharma licensed the antisense oligonucleotide from Ionis Pharmaceuticals for $25 million upfront in 2019 and is currently aiming for an approval decision by regulators for chronic hepatitis B next year. The reemphasis on bepirovirsen came as GSK disclosed this morning that it has discontinued work on GSK3528869. The company had been holding out hopes that the candidate could be another functional cure for the infection—meaning it reduces hepatitis B virus DNA and viral proteins to undetectable levels. This stands in contrast to currently available oral antiviral therapies, which only suppress the virus.But those hopes for GSK3528869 appeared to be dashed in December when GSK terminated a phase 1/2 chronic hepatitis B study after the therapeutic vaccine regimen failed to meet the efficacy endpoint. The study tested different dose levels and sequences—and included placebo—but the idea was to prime the immune system with a viral vector encoding hepatitis B protein antigens, boost the immune system with a different vaccine and administer adjuvants to enhance the response.At the time, the pharma still had another study of GSK3528869 listed as active on the federal trial database. That study was evaluating the effect of giving vaccines to prime and boost the immune system—and adjuvants to enhance the response—after patients have received GSK’s bepirovirsen. But GSK confirmed in its earnings documents (PDF) today that it won’t be taking GSK3528869 forward.GSK isn’t the only pharma to have struggled with hepatitis B candidates in the clinic. Roche axed phase 1 and 2 trials in a recent pipeline cull, while Altimmune dropped a drug candidate after phase 2 data disappointed, and Ascletis Pharma stopped a hepatitis B program after the asset flopped in another indication.While bepirovirsen is taking priority, GSK still has a number of other assets in clinical development for chronic hepatitis B, including the hepatitis B virus-targeted siRNA GSK5637608, the PAPD5/PAPD7 inhibitor GSK3965193 and the TLR8 agonist GSK5251738. GSK also disclosed this morning that it had removed a capsid protein inhibitor for HIV called VH4004280 from its phase 2 pipeline. The company still has another HIV capsid protein inhibitor in multiple clinical trials in the form of VH3739937.The final drug to be pulled is the phase 1-stage GSK2556286, which is designed to inhibit the intracellular growth of Mycobacterium tuberculosis. The pharma has other tuberculosis candidates in the clinic in the form of the leucyl t-RNA synthetase inhibitor ganfeborole, the ethionamide booster alpibectir and the serine beta lactamase inhibitor sanfetrinem cilexetil. When it came to M&A, Walmsley told journalists on the media call that the company “continues to add new opportunities through targeted business development.” She pointed to the acquisition of Boston-based cancer-focused biotech IDRx last month as “a good example of what we want to do here.”

$GSK drops one potential \'functional cure\' for hep B as it goes all-in on bepirovirsen$

VaccinePhase 2AcquisitionOligonucleotidesiRNA

29 Nov 2023

·www.biospace.com

Arrowhead Pharmaceuticals Reports Fiscal 2023 Year End Results

- Conference Call and Webcast Today, November 29, 2023, at 4:30 p.m. ET PASADENA, Calif.--(BUSINESS WIRE)-- Arrowhead Pharmaceuticals, Inc., (NASDAQ: ARWR) today announced financial results for its fiscal year ended September 30, 2023. The company is hosting a conference call today, November 29, 2023, at 4:30 p.m. ET to discuss the results. Webcast and Conference Call and Details Investors may access a live audio webcast on the Company's website at . A replay of the webcast will be available approximately two hours after the conclusion of the call. For analysts that wish to participate in the conference call, please register at . Once registered, you will receive the dial-in number and a personalized PIN code that will be required to access the call. Selected Recent Events Presented new Phase 2 clinical data from the ongoing SHASTA-2 and MUIR studies of plozasiran (ARO-APOC3) and the ARCHES-2 study of zodasiran (ARO-ANG3) at the American Heart Association (AHA) Scientific Sessions. Key updates included: Plozasiran achieved mean max reductions of up to 90% in APOC3, 87% in triglycerides, and 63% in remnant cholesterol in patients with severe hypertriglyceridemia. In patients with mixed dyslipidemia, plozasiran achieved a mean max reduction in APOC3 of up to 89%, leading to robust and durable improvements in multiple atherogenic lipoproteins Zodasiran treatment resulted in substantial reductions of ANGPTL3, triglycerides, and LDL-cholesterol in patients with mixed dyslipidemia Plozasiran and zodasiran continue to show favorable safety pro Treatment emergent adverse events reported to date reflect the comorbidities and underlying conditions of the study populations Hosted a webinar featuring experts in the treatment and management of lipid and lipoprotein disorders to discuss plozasiran Daniel Gaudet, MD, PhD, Professor of Medicine at Université de Montréal, discussed plozasiran in the context of the current treatment landscape for severe hypertriglyceridemia Børge Nordestgaard, MD, Professor & Chief Physician, Copenhagen University Hospital, University of Copenhagen, Denmark, discussed the emergent role of remnant cholesterol in cardiovascular disease Steven Nissen, MD, Chief Academic Officer for the Heart and Vascular Institute at the Cleveland Clinic, discussed why the decrease in atherogenic lipoproteins observed with plozasiran has the potential to prevent cardiovascular outcomes Completed chronic GLP toxicology for pulmonary candidates ARO-RAGE, designed to reduce expression of the receptor for advanced glycation end products as a potential treatment for inflammatory pulmonary diseases, and ARO-MMP7, designed to reduce expression of matrix metalloproteinase 7 as a potential treatment for idiopathic pulmonary fibrosis Results were highly encouraging and suggest sufficient safety margins to proceed to Phase 2 studies Presented data on the company’s pipeline of pulmonary targeted RNAi therapeutic candidates, including clinical results for ARO-RAGE, at the European Respiratory Society (ERS) International Congress 2023. Key results included: Late-breaking clinical data for ARO-RAGE demonstrated deep and durable gene silencing in healthy volunteers and in patients with asthma Promising preclinical data across multiple pulmonary programs suggested broad potential applications for Arrowhead’s TRiM™ platform Filed for regulatory clearance to initiate a Phase 1/2a study of Arrowhead’s second RNAi therapeutic candidate targeting skeletal muscle, ARO-DM1, for patients with type 1 myotonic dystrophy Announced that GSK plc reached an agreement with Janssen Pharmaceuticals, Inc. (Janssen), a Johnson & Johnson company, to transfer exclusive worldwide rights to further develop and commercialize JNJ-3989. JNJ-3989 (formerly ARO-HBV) was initially in-licensed by Janssen from Arrowhead in 2018 Selected Fiscal 2023 Year End Financial Results ARROWHEAD PHARMACEUTICALS, INC. CONSOLIDATED CONDENSED FINANCIAL INFORMATION (in thousands, except per share amounts) OPERATING SUMMARY Year Ended September 30, 2023 2022 Revenue $ 240,735 $ 243,231 Operating Expenses: Research and development 353,188 297,307 General and administrative expenses 92,549 124,431 Total Operating Expenses 445,737 421,738 Operating loss (205,002 ) (178,507 ) Interest income 15,299 5,033 Interest expense (18,326 ) - Other, net 1,538 765 Loss before income tax expense and noncontrolling interest (206,491 ) (172,709 ) Income tax expense 2,784 3,785 Net loss including noncontrolling interest (209,275 ) (176,494 ) Net loss attributable to noncontrolling interest, net of tax (4,000 ) (431 ) Net loss attributable to Arrowhead Pharmaceuticals, Inc. $ (205,275 ) $ (176,063 ) Net loss per share attributable to Arrowhead Pharmaceuticals, Inc. - Diluted $ (1.92 ) $ (1.67 ) Weighted-average shares used in calculating - Diluted 106,750 105,426 FINANCIAL POSITION SUMMARY September 30, 2023 2022 Cash, cash equivalents and restricted cash $ 110,891 $ 108,005 Investments 292,735 374,263 Total cash resources (cash and investments) 403,626 482,268 Other assets 361,926 209,671 Total Assets $ 765,552 $ 691,939 Current deferred revenue $ 866 $ 74,099 Long-term deferred revenue - 55,950 Other liabilities 477,524 143,551 Total Liabilities $ 478,390 $ 273,600 Total Arrowhead Pharmaceuticals, Inc. Stockholders' Equity $ 271,343 $ 398,520 Noncontrolling Interest 15,819 19,819 Total Noncontrolling Interest and Stockholders' Equity $ 287,162 $ 418,339 Total Liabilities, Noncontrolling Interest and Stockholders' Equity $ 765,552 $ 691,939 Shares Outstanding 107,312 105,960 About Arrowhead Pharmaceuticals Arrowhead Pharmaceuticals develops medicines that treat intractable diseases by silencing the genes that cause them. Using a broad portfolio of RNA chemistries and efficient modes of delivery, Arrowhead therapies trigger the RNA interference mechanism to induce rapid, deep, and durable knockdown of target genes. RNA interference, or RNAi, is a mechanism present in living cells that inhibits the expression of a specific gene, thereby affecting the production of a specific protein. Arrowhead’s RNAi-based therapeutics leverage this natural pathway of gene silencing. For more information, please visit , or follow us on Twitter @ArrowheadPharma. To be added to the Company's email list and receive news directly, please visit . Safe Harbor Statement under the Private Securities Litigation Reform Act: This news release contains forward-looking statements within the meaning of the "safe harbor" provisions of the Private Securities Litigation Reform Act of 1995. Any statements contained in this release except for historical information may be deemed to be forward-looking statements. Without limiting the generality of the foregoing, words such as “may,” “will,” “expect,” “believe,” “anticipate,” “hope,” “intend,” “plan,” “project,” “could,” “estimate,” “continue,” “target,” “forecast” or “continue” or the negative of these words or other variations thereof or comparable terminology are intended to identify such forward-looking statements. In addition, any statements that refer to projections of our future financial performance, trends in our business, expectations for our product pipeline or product candidates, including anticipated regulatory submissions and clinical program results, prospects or benefits of our collaborations with other companies, or other characterizations of future events or circumstances are forward-looking statements. These forward-looking statements include, but are not limited to, statements about the initiation, timing, progress and results of our preclinical studies and clinical trials, and our research and development programs; our expectations regarding the potential benefits of the partnership, licensing and/or collaboration arrangements and other strategic arrangements and transactions we have entered into or may enter into in the future; our beliefs and expectations regarding milestone, royalty or other payments that could be due to or from third parties under existing agreements; and our estimates regarding future revenues, research and development expenses, capital requirements and payments to third parties. These statements are based upon our current expectations and speak only as of the date hereof. Our actual results may differ materially and adversely from those expressed in any forward-looking statements as a result of numerous factors and uncertainties, including the impact of the ongoing COVID-19 pandemic on our business, the safety and efficacy of our product candidates, decisions of regulatory authorities and the timing thereof, the duration and impact of regulatory delays in our clinical programs, our ability to finance our operations, the likelihood and timing of the receipt of future milestone and licensing fees, the future success of our scientific studies, our ability to successfully develop and commercialize drug candidates, the timing for starting and completing clinical trials, rapid technological change in our markets, the enforcement of our intellectual property rights, and the other risks and uncertainties described in our most recent Annual Report on Form 10-K, subsequent Quarterly Reports on Form 10-Q and other documents filed with the Securities and Exchange Commission from time to time. We assume no obligation to update or revise forward-looking statements to reflect new events or circumstances. Source: Arrowhead Pharmaceuticals, Inc.

Financial StatementClinical ResultAHA

01 Nov 2023

·www.pmlive.com

GSK to acquire exclusive rights to Janssen’s hepatitis B therapy in $1bn deal

GSK and Arrowhead Pharmaceuticals have announced that they have reached an agreement with Janssen Pharmaceuticals to receive exclusive rights to its hepatitis B therapy, JNJ-3989. The Johnson & Johnson company’s investigational hepatitis B virus (HBV)-targeted small interfering ribonucleic acid (siRNA) therapeutic was initially licensed by Janssen from Arrowhead in 2018. Exclusive rights to the liver-targeted siRNA antiviral therapy will accelerate the expansion of GSK’s own hepatitis B treatment, bepirovirsen, which is currently in late-stage development, the company said. Under the terms of the deal, GSK will pay upfront and potential milestone-based payments totalling $1bn to Janssen and Arrowhead to acquire exclusive rights and obligations under the current license agreement between both companies. Janssen will continue to be responsible for the ongoing clinical trials of JNJ-3989 at its own expense and GSK will be responsible for future development and commercialisation activities. Additionally, tiered royalties on net dates pursuant to the original agreement will go to Arrowhead. GSK intends to evaluate JNJ-3989 in combination with its investigational antisense oligonucleotide, bepirovirsen, for the treatment of adult non-cirrhotic patients with chronic hepatitis B (CHB) on nucleos(t)ide analogue (NA) therapy. JNJ-3839 has the potential to move into a phase 2 sequential regimen trial with GSK’s bepirovirsen in 2024. Hepatitis B is a viral infection of the liver, caused by HBV, that can result in both acute and chronic liver disease. Estimated to affect 300 million people worldwide, CHB is a long-lasting infection and occurs when the body’s immune system is unable to fight off the virus and it persists in the blood and liver. Tony Wood, chief scientific officer at GSK, said: "[The company is] excited to build on promising results already demonstrated with bepirovirsen to investigate a novel sequential regimen with JNJ-3989. “We believe this approach could redefine the treatment paradigm for CHB by helping even more patients achieve functional cure." Arrowhead’s president and chief executive officer, Chris Anzalone, commented: “We… look forward to seeing this programme progress towards the goal of potentially helping the millions of patients with CHB worldwide without adequate treatment options.”

License out/inOligonucleotide

100 Deals associated with Daplusiran/Tomligisiran

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Hepatitis D, Chronic	Phase 2	US	Janssen Research & Development LLC	28 Sep 2020
Hepatitis D, Chronic	Phase 2	US	Johnson & Johnson (China) Investment Ltd.	28 Sep 2020
Hepatitis D, Chronic	Phase 2	JP	Janssen Research & Development LLC	28 Sep 2020
Hepatitis D, Chronic	Phase 2	JP	Johnson & Johnson (China) Investment Ltd.	28 Sep 2020
Hepatitis D, Chronic	Phase 2	AU	Janssen Research & Development LLC	28 Sep 2020
Hepatitis D, Chronic	Phase 2	AU	Johnson & Johnson (China) Investment Ltd.	28 Sep 2020
Hepatitis D, Chronic	Phase 2	BR	Janssen Research & Development LLC	28 Sep 2020
Hepatitis D, Chronic	Phase 2	BR	Johnson & Johnson (China) Investment Ltd.	28 Sep 2020
Hepatitis D, Chronic	Phase 2	FR	Johnson & Johnson (China) Investment Ltd.	28 Sep 2020
Hepatitis D, Chronic	Phase 2	FR	Janssen Research & Development LLC	28 Sep 2020

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT05275023 (OCTOPUS-1, CTgov)	Phase 2	Hepatitis B, Chronic	37	JNJ-73763989 (JNJ-3989)+Nivolumab (JNJ-73763989 (JNJ-3989) + Nivolumab (1 Infusion) + NA)	xwuexxfgie(bvrgurnzsk) = lwevvlemgn zicablueal (eewnegxycn, acxfnrghck - iabrebvdvn) View more	-	10 Feb 2025
				Nivolumab+JNJ-3989 (JNJ-3989 + Nivolumab (3 Infusions) + NA)	xwuexxfgie(bvrgurnzsk) = getlvutqmu zicablueal (eewnegxycn, sgicaakrjb - qmkcwwgyln) View more
NCT04129554 (REEF-2, CTgov)	Phase 2	Hepatitis B, Chronic	130	JNJ-73763989+JNJ-56136379 (Arm 1: JNJ-73763989 (200 Milligrams [mg])+JNJ-56136379 (250 mg)+NA)	jpzqtutnly(rnsusyyoci) = oqnkdrxvzb ehxcqhuemo (cckulfnyoc, ttqxrhuuqa - qjfbnaacnj) View more	-	31 Jul 2024
				Nucleos(t)Ide Analog (Arm 2: Nucleos(t)Ide Analog (NA))	jpzqtutnly(rnsusyyoci) = mzxkumsphv ehxcqhuemo (cckulfnyoc, ztpzvafqcs - hicylxukjt) View more
NCT04667104 (PENGUIN, CTgov)	Phase 2	Hepatitis B, Chronic	48	JNJ-3989+PegIFN-alpha2a+JNJ-6379 (TP 2:JNJ-3989 200 mg+JNJ-6379 250 mg+PegIFN-alpha2a 180 mcg+NA)	xwjzzsqpbn(kdcwgbbzgn) = jcyjqexfnc ubuuvysthu (rrkumofwle, vegbvlmuml - nojagojpwz) View more	-	03 Jul 2024
				JNJ-73763989+JNJ-56136379 (TP 1:JNJ-73763989 200 mg+JNJ-56136379 250 mg+NA)	owrsbybtoi(ebekdcrfyo) = saayxtbbsf imlnqqbxcr (vzymhbxgpg, qkrhhvivdx - yuwckcineo) View more
NCT04129554 (REEF-2, Pubmed) Manual	Phase 2	Hepatitis B, Chronic Hepatitis B e-antigen (HBeAg)-negative \| HBsAg	130	JNJ-73763989-6JNJ-56136379	vuzyqmcbyq(nnilvgxozh) = zxyklohhgz kxnhxtnenf (tiejaftyoc ) View more	Negative	05 Apr 2024
				Placebos for JNJ-3989 and JNJ-6379 + active NA	vuzyqmcbyq(nnilvgxozh) = atdictvzrh kxnhxtnenf (tiejaftyoc ) View more
NCT05005507 (PENGUIN-2, CTgov)	Phase 2	Hepatitis B, Chronic	1	Nucleos(t)Ide Analog (NA)+JNJ-73763989+PegIFN-alpha-2a	zxoubeaxcr(spksuxirhn) = farntsazgp twpirtlnmo (abzsqahdkm, lvqlmcpzip - whoxffgyps) View more	-	06 Mar 2024
NCT04585789 (INSIGHT, CTgov)	Phase 2	Hepatitis B, Chronic	24	NA+TAF+JNJ-73763989+PegIFN-alpha-2a+ETV+JNJ-56136379 (Panel 1)	uvuevdaisn(cwpqhuaizn) = imnpnmahuq hktiniytxz (wtrxtbkiva, phhvhtfwtk - gegngplzrq) View more	-	05 Mar 2024
				NA+TAF+JNJ-73763989+PegIFN-alpha-2a+ETV+JNJ-56136379 (Panel 2)	uvuevdaisn(cwpqhuaizn) = vxanarttox hktiniytxz (wtrxtbkiva, utwblqwkez - kzbjiysynd) View more
NCT03982186 (REEF-1, Pubmed) Manual	Phase 2	Hepatitis B, Chronic First line	470	JNJ-6379+JNJ-3989 (JNJ-3989 dual 40 mg group)	sguyvwggos(hjxohryubh) = mheujiimeg ufxhgqmywz (vcpbcfieph, 2 - 11)	Positive	10 Jul 2023
				JNJ-6379+JNJ-3989 (JNJ-3989 dual 100 mg group)	sguyvwggos(hjxohryubh) = zrxuiyahsi ufxhgqmywz (vcpbcfieph, 10 - 24)
NCT04586439 (Pubmed) Manual	Phase 1	-	18	JNJ 73763989 (100 mg)	qmoelwaesx(qseghcvrpm) = All treatment-emergent adverse events (AEs) were mild and resolved by study end. nxwknuvlsy (jyutyenrwc )	Positive	22 Nov 2022
				JNJ 73763989 (200 mg)
NCT03365947 (Pubmed)	Phase 2	Hepatitis B, Chronic	114	JNJ-3989 plus nucleos(t)ide analogue	daqsksvjll(udppwmgyim) = All treatments were well-tolerated, with all five serious adverse events considered unrelated to study drugs xldftnjexa (pzfjmffgpe ) View more	Positive	20 Jul 2022
				JNJ-3989 Q4W plus JNJ-6379 plus nucleos(t)ide analogue
NCT04129554 (REEF-2, Corporate Publications) Manual	Phase 2	Hepatitis B, Chronic HBeAg Negative	130	ETV/TDF/TAF+JNJ 73763989+JNJ 56136379	ahtkohbkoh(nnerehfqwz) = plrvodlmnl evxtgokgpd (toyqynfbvl ) View more	Negative	27 Jun 2022
				ETV/TDF/TAF+Placebo+Placebo	ahtkohbkoh(nnerehfqwz) = zvsvarkalz evxtgokgpd (toyqynfbvl ) View more

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