A Phase 2b Multicenter, Randomized, Open-Label Study Comparing the Efficacy, Safety, PK, and Tolerability of VH3810109, Administered Either Intravenously Or As A Subcutaneous Infusion With rHuPH20, in Combination With CAB LA to Standard of Care in Virologically Suppressed Adults Living With HIV

The study aims at evaluating the efficacy of VH3810109, dosed in accordance with the dosing schedule as either intravenous (IV) infusion or subcutaneous (SC) infusion with recombinant hyaluronidase (rHuPH20), in combination with cabotegravir (CAB) intramuscular (IM) dosed in accordance with the dosing schedule in virologically suppressed, Antiretroviral therapy (ART)-experienced adult participants living with HIV.

Start Date17 Aug 2023

Sponsor / Collaborator

ViiV Healthcare Ltd.

NCT05291520 / CompletedPhase 1

A Phase 1, Open-Label, Single-Dose Study of the Safety and Pharmacokinetics of a Human Monoclonal Antibody, GSK3810109, Administered Either Subcutaneously or Intravenously With Recombinant Human Hyaluronidase PH20 (rHuPH20) to Healthy Adults

An open-label, two part study to assess the safety, tolerability, and PK of VH3810109 in healthy adult participants. Participants will receive a single SC or IV dose of VH3810109 co-administered with rHuPH20 and will be followed up for 24 weeks.

Start Date23 Feb 2022

Sponsor / Collaborator

ViiV Healthcare Ltd.

NCT04871113 / CompletedPhase 2

A Phase 2a Multicentre, Randomized, Open-Label, Two-Part Adaptive Design Study to Evaluate the Antiviral Effect, Safety and Tolerability of GSK3810109A, an HIV-1 Specific Broadly Neutralizing Human Monoclonal Antibody in Antiretroviral-naïve HIV-1-Infected Adults

This study is to evaluate antiviral activity, efficacy, safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of GSK3810109A in HIV-1 infected treatment naive adults. Participants will receive a single dose of GSK3810109A administered either intravenously (IV) or subcutaneously (SC). The study includes a screening phase, a randomized monotherapy phase and a standard of care follow-up phase.

Start Date22 Jun 2021

Sponsor / Collaborator

ViiV Healthcare Ltd.

100 Clinical Results associated with GSK-3810109

100 Translational Medicine associated with GSK-3810109

100 Patents (Medical) associated with GSK-3810109

Literatures (Medical) associated with GSK-3810109

31 Dec 2023·mAbs

Improved pharmacokinetics of HIV-neutralizing VRC01-class antibodies achieved by reduction of net positive charge on variable domain

Article

Author: Zhang, Baoshan ; Yang, Eun Sung ; Louder, Mark K ; Schaub, Andrew J ; Bender, Michael F ; Lusso, Paolo ; McKee, Krisha ; Pegu, Amarendra ; Asokan, Mangaiarkarasi ; Liu, Qingbo ; Kwong, Peter D ; Rawi, Reda ; Kwon, Young D ; Shen, Chen-Hsiang ; Mascola, John R ; Liu, Tracy ; Reveiz, Mateo ; Lin, Bob C ; Doria-Rose, Nicole A

The amino-acid composition of the immunoglobulin variable region has been observed to impact antibody pharmacokinetics (PK). Here, we sought to improve the PK of the broad HIV-1-neutralizing VRC01-class antibodies, VRC07-523LS and N6LS, by reducing the net positive charge in their variable domains. We used a structure-guided approach to generate a panel of antibody variants incorporating select Arg or Lys substituted to Asp, Gln, Glu, or Ser. The engineered variants exhibited reduced affinity to heparin, reduced polyreactivity, and improved PK in human FcRn-transgenic mice. One variant, VRC07-523LS.v34, with three charge substitutions, had an observed in vivo half-life and an estimated human half-life of 10.8 and 60 days, respectively (versus 5.4 and 38 days for VRC07-523LS) and retained functionality, neutralizing 92% of a 208-strain panel at a geometric mean IC₈₀ <1 µg/mL. Another variant, N6LS.C49, with two charge substitutions, had an observed in vivo half-life and an estimated human half-life of 14.5 and 80 days (versus 9.0 and 44 days for N6LS) and neutralized ~80% of 208 strains at a geometric mean IC₈₀ <1 µg/mL. Since Arg and Lys residues are prevalent in human antibodies, we propose substitution of select Arg or Lys with Asp, Gln, Glu, or Ser in the framework region as a general means to improve PK of therapeutic antibodies.

15 Aug 2017·Journal of virologyQ2 · MEDICINE

Virological Control by the CD4-Binding Site Antibody N6 in Simian-Human Immunodeficiency Virus-Infected Rhesus Monkeys

Q2 · MEDICINE

Article

Author: Callow, Katherine ; Molloy, Katherine ; Schmidt, Stephen D. ; Chandrashekar, Abishek ; Keele, Brandon F. ; Pegu, Amarendra ; Chen, Xuejun ; Julg, Boris ; Connors, Mark ; Huang, Jinghe ; Mascola, John R. ; Barouch, Dan H. ; Abbink, Peter ; Seaman, Michael S. ; Liu, Jinyan ; Brinkman, Amanda ; Mojta, Shanell ; Wang, Keyun ; Koup, Richard A.

ABSTRACT:

Passive immunotherapy against HIV-1 will most likely require broadly neutralizing antibodies (bnAbs) with maximum breadth and potency to ensure therapeutic efficacy. Recently, the novel CD4 binding site antibody N6 demonstrated extraordinary neutralization breadth and potency against large panels of cross-clade pseudoviruses. We evaluated the in vivo antiviral activity of N6-LS, alone or in combination with the established V3-glycan antibody PGT121, in chronically simian-human immunodeficiency virus (SHIV)-SF162P3-infected macaques. A single dose of N6-LS suppressed plasma viral loads in 4 out of 5 animals at day 7, while the combination of both antibodies suppressed all animals. The combination of both antibodies had no additive antiviral effect compared to a single dose of PGT121, potentially reflecting the nearly 10-fold-higher potency of PGT121 against this SHIV. Viral rebound occurred in the majority of suppressed animals and was linked to declining plasma bnAb levels over time. In addition to the effect on plasma viremia, bnAb administration resulted in significantly reduced proviral DNA levels in PBMCs after 2 weeks and in lymph nodes after 10 weeks. Autologous neutralizing antibody (nAb) responses and CD8 + T-cell responses were not significantly enhanced in the bnAb-treated animals compared to control animals, arguing against their contribution to the viral effects observed. These results confirm the robust antiviral activity of N6-LS in vivo , supporting the further clinical development of this antibody. IMPORTANCE Monocloncal antibodies (MAbs) are being considered for passive immunotherapy of HIV-1 infection. A critical requirement for such strategies is the identification of MAbs that recognize the diversity of variants within circulating but also reservoir viruses, and MAb combinations might be needed to achieve this goal. This study evaluates the novel bnAb N6-LS alone or in combination with the bnAb PGT121, in rhesus macaques that were chronically infected with SHIV. The results demonstrate that N6-LS potently suppressed plasma viral loads in the majority of animals but that the combination with PGT121 was not superior to PGT121 alone in delaying time to viral rebound or reducing peripheral blood mononuclear cell (PBMC) or lymph node proviral DNA levels. The occurrence of viral escape variants in an N6-LS-monotreated animal, however, argues for the need to maximize breadth and antiviral efficacy by combining bnAbs for therapeutic indications.

PLoS pathogensQ1 · MEDICINE

TLR7 agonist, N6-LS and PGT121 delayed viral rebound in SHIV-infected macaques after antiretroviral therapy interruption

Q1 · MEDICINE

ArticleOA

Author: Inthawong, Dutsadee ; Pegu, Amarendra ; Robb, Merlin L ; Imerbsin, Rawiwan ; Vasan, Sandhya ; Hsu, Denise C ; Geleziunas, Romas ; Sopanaporn, Jumpol ; Visudhiphan, Pornsuk ; Silsorn, Decha ; Shi, Wei ; Michael, Nelson L ; Barouch, Dan H ; Schuetz, Alexandra ; Chuenarom, Weerawan ; Keawboon, Boot ; Mascola, John R ; Koup, Richard A

Toll-like receptor 7 (TLR7) agonist and PGT121 (broadly neutralizing antibody, bnAb) administration previously delayed viral rebound and induced SHIV remission. We evaluated the impact of GS-986 (TLR7 agonist) and dual bnAbs on viral rebound after antiretroviral therapy (ART) interruption. Rhesus macaques inoculated with SHIV-1157ipd3N4 were initiated on daily suppressive ART from Day 14 post SHIV inoculation. Active arm animals (n = 8) received GS-986, N6-LS and PGT121 after plasma viral suppression, starting from week 14. GS-986 induced immune activation and SHIV-specific T cell responses but not viral expression in all the active arm animals. After ART interruption, median time to viral rebound was 6 weeks in the active and 3 weeks in the control arm (p = 0.024). In this animal model, the administration of the combination of GS-986 and dual bnAbs was associated with a modest delay in viral rebound. This strategy should be further evaluated to better understand the underlying mechanisms for the induction of virus-specific immune responses and delay in viral rebound.

News (Medical) associated with GSK-3810109

28 Feb 2024

·www.biospace.com

ViiV Healthcare to present data for its next generation of ultra long-acting treatments for HIV

Other key data to be presented from ViiV Healthcare’s innovative pipeline and portfolio include the exploration of different mechanisms of action through broadly neutralising antibodies as well as real-world insights from established long-acting and 2-drug regimens LONDON--(BUSINESS WIRE)-- ViiV Healthcare, the global specialist HIV company majority owned by GSK, with Pfizer and Shionogi as shareholders, today announced the presentation of 64 abstracts that includes highlights of the company’s next-generation pipeline advancements, alongside data from its diverse portfolio of marketed HIV treatment and prevention options at the Conference on Retroviruses and Opportunistic Infections (CROI 2024) being held in Denver, Colorado, from 3 – 6 March 2024. Kimberly Smith, M.D., MPH, Head of Research & Development at ViiV Healthcare, said: “As leaders in developing long-acting injectables for the treatment of HIV, we’re excited to present new data setting the stage for ViiV’s next generation of medicines and demonstrating how key pipeline assets will target HIV in different ways. These findings, as well as the breadth of data we’ll present on our marketed products, including new interim results from the LATITUDE study, reflect a portfolio and future-looking pipeline focused on ending the HIV epidemic. We look forward to sharing them with the scientific and HIV communities at CROI 2024.” Key abstracts to be presented at CROI 2024 by ViiV Healthcare and its study partners will include: Data introducing our next generation of potential ultra long-acting medicines for HIV: ViiV Healthcare will share findings from a phase I study evaluating different formulations of cabotegravir and their potential for dosing every four months. The ongoing, open-label, single-dose, dose-escalation phase I study in 70 healthy adults assessed both the 200 mg/mL formulation of cabotegravir in combination with recombinant human hyaluronidase PH20 (rHuPH20), as well as a new formulation of cabotegravir (CAB ULA) administered by itself.1 Researchers will share safety and pharmacokinetic findings from both ultra long-acting approaches and their potential for future clinical development. Findings advancing different mechanisms of action in HIV research: New phase IIa findings from the BANNER study of VH3810109 (N6LS), an investigational, broadly neutralising antibody (bNAb), will be presented. Researchers will share findings of the bNAb administered intravenously and the first efficacy findings of its subcutaneous administration.2 Findings from the SPAN study of N6LS, examining the safety and tolerability of the highest subcutaneous and intravenous N6LS doses administered to date, with and without PH20, will also be presented.3 Additionally, efficacy and safety data from a non-ViiV owned bNAb asset, VRC07-523LS, in a phase II, open-label clinical trial used in combination with long-acting CAB for maintenance antiretroviral therapy (ART) will be presented.4 New data on long-acting therapy vs daily oral standard of care, in traditionally non-adherent populations: Interim analysis of the LATITUDE phase III trial will be presented showing that, the injectable antiretroviral treatment for HIV, Cabenuva (cabotegravir and rilpivirine [CAB+RPV LA]), demonstrates superior efficacy compared to daily oral standard of care (SOC) in individuals with a history of antiretroviral adherence challenges. The NIAID/ACTG also announced a modification to the study, where further randomisation has been stopped and participants in the SOC arm are being given the option to switch to the long-acting therapy arm.5 Real-world evidence from across our treatment and prevention portfolios: New findings from SEARCH, a randomised study evaluating the real-world impact of the inclusion of long-acting cabotegravir for PrEP in an HIV prevention coverage package compared to the standard-of-care of oral PrEP and PEP alone in rural Uganda and Kenya, will also be presented.6 Real-world evidence findings for the complete long-acting HIV treatment regimen Cabenuva will be presented from the OPERA cohort examining ART-experienced, virally suppressed adults living with HIV who switched to CAB+RPV LA or to an oral regimen.7 Findings for the 2-drug regimen, Dovato (dolutegravir, lamivudine [DTG/3TC]), will include the InfCare HIV study, which presents three-year switch data, from 3-drug regimen to Dovato, in a long-term real-world Swedish cohort.8 This study adds to the body of real-world evidence to date that includes more than 40,000 people living with HIV.9 Here is a list of ViiV Healthcare-sponsored or supported studies to be presented at CROI 2024: Title First Author Presentation Number Presentation Dolutegravir A single once-daily ABC/DTG/3TC tablet predicts safe and effective exposures in children 3 to <6kg H. Chandasana 02770 Poster Tuesday, March 5 2:30-4:00pm MST Population pharmacokinetics of ABC/DTG/3TC FDC to support dosing in peds with HIV-1 (IMPAACT 2019) H. Chandasana 03110 Poster Tuesday, March 5:30-4:00pm MST Dolutegravir and growth in pediatric populations with HIV-1: IMPAACT P1093 and IMPAACT 2019 M. McKenna 01783 Poster Tuesday, March 5 2:30-4:00pm MST Switching to DTG+3TC vs 3-drug regimens in routine clinical care: long-term Swedish data E. Sörstedt 01838 Poster Tuesday, March 5 2:30-4:00pm MST Temporal trends of cardiovascular disease incidence in people with HIV from 2001-2021 N. Jaschinski 02263 Poster Tuesday, March 5 2:30-4:00pm MST Increased cancer risk with low CD4 counts persists despite over 2 years of virological suppression J. Hoy 01462 Poster Wednesday, March 6 2:30-4:00pm MST Cabotegravir for Treatment Long-acting Injectable CAB/RPV is Superior to Oral ART in PWH with adherence challenges: ACTG A5359 A. Rana 03579 Oral Wednesday, March 6 12:51-1:00pm MST Real-world utilization of cabotegravir + rilpivirine in the US: data from Trio Health cohort J. J. Eron 01374 Poster Monday, March 4 2:30-4:00pm MST Real-world effectiveness of cabotegravir + rilpivirine vs. standard of care oral regimens in the US R. K. Hsu 01952 Poster Monday, March 4 2:30-4:00pm MST HIV-1 RNA blips and low-level viral replication: SOLAR (CAB+RPV LA vs. BIC/FTC/TAF) C. Latham 00138 Poster Monday, March 4 2:30-4:00pm MST Model based comparison of cabotegravir pharmacokinetics following thigh and gluteal injections K. Han 03157 Poster Wednesday, March 6 2:30-4:00pm MST Cabotegravir for PrEP SEARCH Randomized trial of Dynamic Choice HIV Prevention including injectable cabotegravir (CAB-LA) J. Kabami 03405 Late-Breaker Oral Tuesday, March 5 10:00-12:00pm MST Pre-exposure prophylaxis with cabotegravir long-acting injectable in the OPERA cohort A. Mills 01400 Poster Monday, March 4 2:30-4:00pm MST Real-world use of cabotegravir long acting for pre-exposure prophylaxis: TRIO cohort K. Mayer 01907 Poster Monday, March 4 2:30-4:00pm MST Cabotegravir PopPK analysis of adults and adolescents living with HIV or at risk for HIV receiving PrEP Y. Lin 03038 Poster Tuesday, March 5 2:30-4:00pm MST Interest in long-acting injectable PrEP among transgender women in the United States E. E. Cooney 00621 Poster Wednesday, March 6 2:30-4:00pm MST Healthcare staff acceptability and feasibility of telehealth delivery of cabotegravir for PrEP A. Liu 03080 Poster Wednesday, March 6 2:30-4:00pm MST Fostemsavir Temsavir treatment enhances bNAb recognition and subsequent clearance of HIV-1 infected cells R. Ferris 02971 Poster Monday, March 4 2:30-4:00pm MST Pipeline: Ultra Long-Acting Cabotegravir Phase I study of cabotegravir long-acting injectable formulations supports ≥4-monthly dose interval K. Han 00251 Oral Monday, March 4 10:00-12:00pm MST Pipeline: Broadly Neutralising Antibodies VH3810109 (N6LS) in antiretroviral therapy–naive adults with HIV-1: phase IIa BANNER efficacy data P. Leone 01911 Oral Monday, March 4 10:00-12:00pm MST Safety and efficacy of VRC07-523LS plus long-acting cabotegravir in the phase 2 ACTG A5357 Trial B. Taiwo 02254 Oral Monday, March 4 10:00-12:00pm MST High-dose VH3810109 (N6LS) ± recombinant human hyaluronidase PH20: phase I SPAN study safety results B. Win 01988 Poster Wednesday, March 6 2:30-4:00pm MST Pipeline: Maturation Inhibitors Next-generation maturation inhibitor GSK3640254 showed broad spectrum potency without MI resistance B. McAuliffe 03095 Poster Wednesday, March 6 2:30-4:00pm MST The preclinical pro maturation inhibitor VH3739937 J. Jeffrey 02819 Poster Wednesday, March 6 2:30-4:00pm MST General HIV Resistance in young children newly diagnosed with HIV in Western Cape, South Africa K. Anderson 01012 Poster Tuesday, March 5 2:30-4:00pm MST DOVATO (dolutegravir and lamivudine) tablets INDICATION Dovato is indicated as a complete regimen to treat HIV-1 infection in adults with no antiretroviral (ARV) treatment history or to replace the current ARV regimen in those who are virologically suppressed (HIV-1 RNA <50 copies/mL) on a stable ARV regimen with no history of treatment failure and no known resistance to any component of Dovato. IMPORTANT SAFETY INFORMATION BOXED WARNING: PATIENTS CO-INFECTED WITH HEPATITIS B VIRUS (HBV) AND HIV-1: EMERGENCE OF LAMIVUDINE-RESISTANT HBV AND EXACERBATIONS OF HBV All patients with HIV-1 should be tested for the presence of HBV prior to or when initiating Dovato. Emergence of lamivudine-resistant HBV variants associated with lamivudine-containing antiretroviral regimens has been reported. If Dovato is used in patients co-infected with HIV-1 and HBV, additional treatment should be considered for appropriate treatment of chronic HBV; otherwise, consider an alternative regimen. Severe acute exacerbations of HBV have been reported in patients who are co-infected with HIV-1 and HBV and have discontinued lamivudine, a component of Dovato. Closely monitor hepatic function in these patients and, if appropriate, initiate anti-HBV treatment. CONTRAINDICATIONS Do not use Dovato in patients with previous hypersensitivity reaction to dolutegravir or lamivudine Do not use Dovato in patients receiving dofetilide WARNINGS AND PRECAUTIONS Hypersensitivity Reactions: Hypersensitivity reactions have been reported with dolutegravir and were characterized by rash, constitutional findings, and sometimes organ dysfunction, including liver injury Discontinue Dovato immediately if signs or symptoms of severe skin or hypersensitivity reactions develop, as a delay in stopping treatment may result in a life-threatening reaction. Clinical status, including liver aminotransferases, should be monitored and appropriate therapy initiated Hepatotoxicity: Hepatic adverse events have been reported, including cases of hepatic toxicity (elevated serum liver biochemistries, hepatitis, and acute liver failure), in patients receiving a dolutegravir-containing regimen without pre-existing hepatic disease or other identifiable risk factors Patients with underlying hepatitis B or C or marked elevations in transaminases prior to treatment may be at increased risk for worsening or development of transaminase elevations with use of Dovato. In some cases, the elevations in transaminases were consistent with immune reconstitution syndrome or hepatitis B reactivation, particularly in the setting where anti-hepatitis therapy was withdrawn Monitoring for hepatotoxicity is recommended Embryo Fetal Toxicity: Assess the risks and benefits of Dovato and discuss with the patient to determine if an alternative treatment should be considered at the time of conception through the first trimester of pregnancy due to the risk of neural tube defects Pregnancy testing is recommended before initiation of Dovato. Individuals of childbearing potential should be counseled on the consistent use of effective contraception Lactic Acidosis and Severe Hepatomegaly With Steatosis: Fatal cases have been reported with the use of nucleoside analogs, including lamivudine. Discontinue Dovato if clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity develop, including hepatomegaly and steatosis in the absence of marked transaminase elevations. Adverse Reactions or Loss of Virologic Response Due to Drug Interactions with concomitant use of Dovato and other drugs may occur (see Contraindications and Drug interactions). Immune Reconstitution Syndrome, including the occurrence of autoimmune disorders with variable time to onset, has been reported with the use of Dovato. Adverse reactions The most common adverse reactions (incidence ≥2%, all grades) with Dovato were headache (3%), nausea (2%), diarrhea (2%), insomnia (2%), fatigue (2%), and anxiety (2%). Drug interactions Consult full Prescribing Information for Dovato for more information on potentially significant drug interactions Dovato is a complete regimen. Coadministration with other antiretroviral medications for the treatment of HIV-1 infection is not recommended Drugs that induce or inhibit CYP3A or UGT1A1 may affect the plasma concentrations of dolutegravir Administer Dovato 2 hours before or 6 hours after taking polyvalent cation-containing antacids or laxatives, sucralfate, oral supplements containing iron or calcium, or buffered medications. Alternatively, Dovato and supplements containing calcium or iron can be taken with food Use in specific populations Pregnancy: There are insufficient human data on the use of Dovato during pregnancy to definitively assess a drug-associated risk for birth defects and miscarriage. An Antiretroviral Pregnancy Registry has been established. Advise individuals of childbearing potential of the potential risk of neural tube defects. Assess the risks and benefits of Dovato and discuss with the patient to determine if an alternative treatment should be considered at the time of conception through the first trimester of pregnancy or if pregnancy is confirmed in the first trimester Lactation: Breastfeeding is not recommended due to the potential for HIV-1 transmission, developing viral resistance in HIV-positive infants, and adverse reactions in a breastfed infant Females and Males of Reproductive Potential: Pregnancy testing is recommended before initiation of Dovato. Counsel individuals of childbearing potential taking Dovato on the consistent use of effective contraception Renal Impairment: Dovato is not recommended for patients with creatinine clearance <30 mL/min. Patients with a sustained creatinine clearance between 30 and 49 mL/min should be monitored for hematologic toxicities, which may require a dosage adjustment of lamivudine as an individual component Hepatic Impairment: Dovato is not recommended in patients with severe hepatic impairment (Child-Pugh Score C) For more information, please see full US Prescribing Information for Dovato: https://gskpro.com/content/dam/global/hcpportal/en_US/Prescribing_Information/Dovato/pdf/DOVATO-PI-PIL.PDF CABENUVA (cabotegravir; rilpivirine) extended-release injectable suspensions INDICATION CABENUVA is indicated as a complete regimen for the treatment of HIV-1 infection in adults and adolescents 12 years of age and older and weighing at least 35 kg to replace the current antiretroviral regimen in those who are virologically suppressed (HIV-1 RNA <50 copies/mL) on a stable antiretroviral regimen with no history of treatment failure and with no known or suspected resistance to either cabotegravir or rilpivirine. IMPORTANT SAFETY INFORMATION CONTRAINDICATIONS Do not use CABENUVA in patients with previous hypersensitivity reaction to cabotegravir or rilpivirine Do not use CABENUVA in patients receiving carbamazepine, oxcarbazepine, phenobarbital, phenytoin, rifabutin, rifampin, rifapentine, systemic dexamethasone (>1 dose), and St John’s wort WARNINGS AND PRECAUTIONS Hypersensitivity Reactions: Serious or severe hypersensitivity reactions have been reported in association with other integrase inhibitors and could occur with CABENUVA Hypersensitivity reactions, including cases of drug reaction with eosinophilia and systemic symptoms (DRESS), have been reported during postmarketing experience with rilpivirine-containing regimens. While some skin reactions were accompanied by constitutional symptoms such as fever, other skin reactions were associated with organ dysfunctions, including elevations in hepatic serum biochemistries Discontinue CABENUVA immediately if signs or symptoms of hypersensitivity reactions develop. Clinical status, including liver transaminases, should be monitored and appropriate therapy initiated. Cabotegravir and rilpivirine oral lead-in may be used to help identify patients who may be at risk of a hypersensitivity reaction Post-Injection Reactions: Serious post-injection reactions (reported in less than 1% of subjects) were reported within minutes after the injection of rilpivirine, including dyspnea, bronchospasm, agitation, abdominal cramping, rash/urticaria, dizziness, flushing, sweating, oral numbness, changes in blood pressure, and pain (e.g., back and chest). These events may have been associated with accidental intravenous administration and began to resolve within a few minutes after the injection Carefully follow the Instructions for Use when preparing and administering CABENUVA. The suspensions should be injected slowly via intramuscular injection and avoid accidental intravenous administration. Observe patients briefly (approximately 10 minutes) after the injection. If a post-injection reaction occurs, monitor and treat as clinically indicated Hepatotoxicity: Hepatotoxicity has been reported in patients receiving cabotegravir or rilpivirine with or without known pre-existing hepatic disease or identifiable risk factors Patients with underlying liver disease or marked elevations in transaminases prior to treatment may be at increased risk for worsening or development of transaminase elevations Monitoring of liver chemistries is recommended and treatment with CABENUVA should be discontinued if hepatotoxicity is suspected Depressive Disorders: Depressive disorders (including depressed mood, depression, major depression, mood altered, mood swings, dysphoria, negative thoughts, suicidal ideation, suicide attempt) have been reported with CABENUVA or the individual products Promptly evaluate patients with depressive symptoms Risk of Adverse Reactions or Loss of Virologic Response Due to Drug Interactions: The concomitant use of CABENUVA and other drugs may result in known or potentially significant drug interactions (see Contraindications and Drug Interactions) Rilpivirine doses 3 and 12 times higher than the recommended oral dosage can prolong the QTc interval CABENUVA should be used with caution in combination with drugs with a known risk of Torsade de Pointes Long-Acting Properties and Potential Associated Risks with CABENUVA: Residual concentrations of cabotegravir and rilpivirine may remain in the systemic circulation of patients for prolonged periods (up to 12 months or longer). Select appropriate patients who agree to the required monthly or every-2-month injection dosing schedule because non-adherence could lead to loss of virologic response and development of resistance To minimize the potential risk of developing viral resistance, it is essential to initiate an alternative, fully suppressive antiretroviral regimen no later than 1 month after the final injection doses of CABENUVA when dosed monthly and no later than 2 months after the final injections of CABENUVA when dosed every 2 months. If virologic failure is suspected, switch the patient to an alternative regimen as soon as possible ADVERSE REACTIONS The most common adverse reactions in adults (incidence ≥2%, all grades) treated with CABENUVA were injection site reactions, pyrexia, fatigue, headache, musculoskeletal pain, nausea, sleep disorders, dizziness, and rash The safety of CABENUVA in adolescents is expected to be similar to adults DRUG INTERACTIONS Refer to the applicable full Prescribing Information for important drug interactions with CABENUVA, VOCABRIA (cabotegravir), or EDURANT (rilpivirine) Because CABENUVA is a complete regimen, coadministration with other antiretroviral medications for the treatment of HIV-1 infection is not recommended Drugs that are strong inducers of UGT1A1 or UGT1A9 are expected to decrease the plasma concentrations of cabotegravir. Drugs that induce or inhibit CYP3A may affect the plasma concentrations of rilpivirine CABENUVA should be used with caution in combination with drugs with a known risk of Torsade de Pointes USE IN SPECIFIC POPULATIONS Pregnancy: There are insufficient human data on the use of CABENUVA during pregnancy to adequately assess a drug-associated risk for birth defects and miscarriage. Discuss the benefit-risk of using CABENUVA during pregnancy and conception and consider that cabotegravir and rilpivirine are detected in systemic circulation for up to 12 months or longer after discontinuing injections of CABENUVA. An Antiretroviral Pregnancy Registry has been established Lactation: Potential risks of breastfeeding include HIV-1 transmission, developing viral resistance in HIV-positive infants, and adverse reactions in a breastfed infant For more information, please see full US Prescribing Information for Cabenuva: APRETUDE (cabotegravir) extended-release injectable suspensions INDICATION APRETUDE is indicated in at-risk adults and adolescents weighing at least 35 kg for pre-exposure prophylaxis (PrEP) to reduce the risk of sexually acquired HIV-1 infection. Individuals must have a negative HIV-1 test prior to initiating APRETUDE (with or without an oral lead-in with oral cabotegravir) for HIV-1 PrEP. IMPORTANT SAFETY INFORMATION BOXED WARNING: RISK OF DRUG RESISTANCE WITH USE OF APRETUDE FOR HIV-1 PRE-EXPOSURE PROPHYLAXIS (PrEP) IN UNDIAGNOSED HIV-1 INFECTION Individuals must be tested for HIV-1 infection prior to initiating APRETUDE or oral cabotegravir, and with each subsequent injection of APRETUDE, using a test approved or cleared by the FDA for the diagnosis of acute or primary HIV-1 infection. Drug-resistant HIV-1 variants have been identified with use of APRETUDE by individuals with undiagnosed HIV-1 infection. Do not initiate APRETUDE for HIV-1 PrEP unless negative infection status is confirmed. Individuals who become infected with HIV-1 while receiving APRETUDE for PrEP must transition to a complete HIV-1 treatment regimen. CONTRAINDICATIONS Do not use APRETUDE in individuals: with unknown or positive HIV-1 status with previous hypersensitivity reaction to cabotegravir receiving carbamazepine, oxcarbazepine, phenobarbital, phenytoin, rifampin, and rifapentine WARNINGS AND PRECAUTIONS Comprehensive Management to Reduce the Risk of HIV-1 Infection: Use APRETUDE as part of a comprehensive prevention strategy, including adherence to the administration schedule and safer sex practices, including condoms, to reduce the risk of sexually transmitted infections (STIs). APRETUDE is not always effective in preventing HIV-1 acquisition. Risk for HIV-1 acquisition includes, but is not limited to, condomless sex, past or current STIs, self-identified HIV risk, having sexual partners of unknown HIV-1 viremic status, or sexual activity in a high prevalence area or network. Inform, counsel, and support individuals on the use of other prevention measures (e.g., consistent and correct condom use; knowledge of partner[s] HIV-1 status, including viral suppression status; regular testing for STIs) Use APRETUDE only in individuals confirmed to be HIV-1 negative. HIV-1 resistance substitutions may emerge in individuals with undiagnosed HIV-1 infection who are taking only APRETUDE, because APRETUDE alone does not constitute a complete regimen for HIV-1 treatment. Prior to initiating APRETUDE, ask seronegative individuals about recent (in past month) potential exposure events and evaluate for current or recent signs or symptoms consistent with acute HIV-1 infection (e.g., fever, fatigue, myalgia, skin rash). If recent (<1 month) exposures to HIV-1 are suspected or clinical symptoms consistent with acute HIV-1 infection are present, use a test approved or cleared by the FDA as an aid in the diagnosis of acute HIV-1 infection When using APRETUDE, HIV-1 testing should be repeated prior to each injection and upon diagnosis of any other STIs Additional HIV testing to determine HIV status is needed if an HIV-1 test indicates possible HIV-1 infection or if symptoms consistent with acute HIV-1 infection develop following an exposure event. If HIV-1 infection is confirmed, then transition the individual to a complete HIV-1 treatment Counsel HIV-1 uninfected individuals to strictly adhere to the recommended dosing and testing schedule for APRETUDE Potential Risk of Resistance with APRETUDE: There is a potential risk of developing resistance to APRETUDE if an individual acquires HIV-1 either before, while taking, or following discontinuation of APRETUDE. To minimize this risk, it is essential to clinically reassess individuals for risk of HIV-1 acquisition and to test before each injection to confirm HIV-1–negative status. Individuals who are confirmed to have HIV-1 infection must transition to a complete HIV-1 treatment. If individuals at continuing risk of HIV-1 acquisition discontinue APRETUDE, alternative forms of PrEP should be considered and initiated within 2 months of the final injection of APRETUDE Long-Acting Properties and Potential Associated Risks with APRETUDE: Residual concentrations of cabotegravir may remain in the systemic circulation of individuals for prolonged periods (up to 12 months or longer). Take the prolonged-release characteristics of cabotegravir into consideration and carefully select individuals who agree to the required every-2-month injection dosing schedule because non-adherence or missed doses could lead to HIV-1 acquisition and development of resistance Hypersensitivity Reactions: Serious or severe hypersensitivity reactions have been reported in association with other integrase inhibitors and could occur with APRETUDE Discontinue APRETUDE immediately if signs or symptoms of hypersensitivity reactions develop. Clinical status, including liver transaminases, should be monitored and appropriate therapy initiated Hepatotoxicity: Hepatotoxicity has been reported in a limited number of individuals receiving cabotegravir with or without known pre-existing hepatic disease or identifiable risk factors Clinical and laboratory monitoring should be considered and APRETUDE should be discontinued if hepatotoxicity is suspected and individuals managed as clinically indicated Depressive Disorders: Depressive disorders (including depression, depressed mood, major depression, persistent depressive disorder, suicidal ideation or attempt) have been reported with APRETUDE Promptly evaluate patients with depressive symptoms Risk of Reduced Drug Concentration of APRETUDE Due to Drug Interactions: The concomitant use of APRETUDE and other drugs may result in reduced drug concentration of APRETUDE Refer to the full Prescribing Information for steps to prevent or manage these possible and known significant drug interactions, including dosing recommendations. Consider the potential for drug interactions prior to and during use of, and after discontinuation of APRETUDE; review concomitant medications during use of APRETUDE ADVERSE REACTIONS The most common adverse reactions (incidence ≥1%, all grades) with APRETUDE were injection site reactions, diarrhea, headache, pyrexia, fatigue, sleep disorders, nausea, dizziness, flatulence, abdominal pain, vomiting, myalgia, rash, decreased appetite, somnolence, back pain, and upper respiratory tract infection. DRUG INTERACTIONS Refer to the full Prescribing Information for important drug interactions with APRETUDE Drugs that induce UGT1A1 may significantly decrease the plasma concentrations of cabotegravir USE IN SPECIFIC POPULATIONS Lactation: Assess the benefit-risk of using APRETUDE to the infant while breastfeeding due to the potential for adverse reactions and residual concentrations in the systemic circulation for up to 12 months or longer after discontinuation Pediatrics: Not recommended in individuals weighing less than 35 kg For more information, please see full US Prescribing Information for APRETUDE: RUKOBIA (fostemsavir) extended-release tablets INDICATION RUKOBIA, in combination with other antiretrovirals (ARVs), is indicated to treat HIV-1 infection in heavily treatment-experienced adults with multidrug-resistant HIV-1 infection failing their current ARV regimen due to resistance, intolerance, or safety considerations. IMPORTANT SAFETY INFORMATION CONTRAINDICATIONS Do not use in patients with previous hypersensitivity to fostemsavir or any of the components of RUKOBIA. Do not use RUKOBIA in patients receiving strong cytochrome P450 (CYP)3A inducers, including but not limited to enzalutamide, carbamazepine, phenytoin, rifampin, mitotane, and St John’s wort (Hypericum perforatum). WARNINGS AND PRECAUTIONS Immune Reconstitution Syndrome, including the occurrence of autoimmune disorders with variable time to onset, has been reported with the use of RUKOBIA. QTc Prolongation with Higher than Recommended Dosages: RUKOBIA at 2,400 mg twice daily has been shown to significantly prolong the QTc interval of the electrocardiogram. Use RUKOBIA with caution in patients with a history of QTc interval prolongation or in patients with relevant pre-existing cardiac disease or who are taking drugs with a known risk of Torsade de Pointes. Elderly patients may be more susceptible to drug-induced QT interval prolongation. Elevations in Hepatic Transaminases in Patients with Hepatitis B or C Virus Co-infection: Monitoring of liver chemistries is recommended in patients with hepatitis B and/or C co-infection. Diligence should be applied in initiating or maintaining effective hepatitis B therapy when starting RUKOBIA in patients co-infected with hepatitis B. Adverse Reactions or Loss of Virologic Response Due to Drug Interactions with concomitant use of RUKOBIA and other drugs may occur (see Contraindications and Drug Interactions). Adverse reactions The most common adverse reaction (all grades, randomized cohort) observed in ≥5% of subjects was nausea (10%). 81% of adverse reactions reported with RUKOBIA were mild or moderate in severity. Drug interactions See the full Prescribing Information for RUKOBIA for a complete list of significant drug interactions. Temsavir may increase plasma concentrations of grazoprevir and voxilaprevir. Use an alternative hepatitis C virus regimen if possible. Use the lowest possible starting dose for statins and monitor for statin-associated adverse events. Patients receiving RUKOBIA should not take doses of estrogen-based therapies, including oral contraceptives, that contain more than 30 mcg/day of ethinyl estradiol. Caution is advised particularly in patients with additional risk factors for thromboembolic events. Use in specific populations Pregnancy: There are insufficient human data on the use of RUKOBIA during pregnancy to definitively assess a drug-associated risk for birth defects and miscarriage. An Antiretroviral Pregnancy Registry has been established. Lactation: Breastfeeding is not recommended due to the potential for HIV-1 transmission, developing viral resistance, and adverse reactions in a breastfed infant. For more information, please see full US Prescribing Information for RUKOBIA: About ViiV Healthcare ViiV Healthcare is a global specialist HIV company established in November 2009 by GSK (LSE: GSK) and Pfizer (NYSE: PFE) dedicated to delivering advances in treatment and care for people living with HIV and for people who are at risk of acquiring HIV. Shionogi became a ViiV shareholder in October 2012. The company’s aims are to take a deeper and broader interest in HIV and AIDS than any company has done before and take a new approach to deliver effective and innovative medicines for HIV treatment and prevention, as well as support communities affected by HIV. For more information on the company, its management, portfolio, pipeline, and commitment, please visit viivhealthcare.com. About GSK GSK is a global biopharma company with a purpose to unite science, technology, and talent to get ahead of disease together. Find out more at gsk.com. Cautionary statement regarding forward-looking statements GSK cautions investors that any forward-looking statements or projections made by GSK, including those made in this announcement, are subject to risks and uncertainties that may cause actual results to differ materially from those projected. Such factors include, but are not limited to, those described under Item 3.D “Risk factors” in the company's Annual Report on Form 20-F for 2022, and Q4 Results for 2023. Registered in England & Wales: GSK plc ViiV No. 3888792 Healthcare Limited No. 06876960 Registered Office: GSK plc 980 Great West Road Brentford, Middlesex United Kingdom TW8 9GS ViiV Healthcare Limited GSK Medicines Research Centre Gunnels Wood Road, Stevenage United Kingdom SG1 2NY References 1 Han, et al. Phase I Study of Cabotegravir Long-Acting Injectable Formulations Supports ≥4-Monthly Dose Interval. Presented at 31st Conference on Retroviruses and Opportunistic Infections (CROI). March 2024. 2 Leone, et al. VH3810109 (N6LS) in Antiretroviral Therapy–Naive Adults With HIV-1: Phase IIa BANNER Efficacy Data. Presented at 31st Conference on Retroviruses and Opportunistic Infections (CROI). March 2024. 3 Win, et al. High-Dose VH3810109 (N6LS) ± Recombinant Human Hyaluronidase PH20: Phase I SPAN Study Safety Results. Presented at 31st Conference on Retroviruses and Opportunistic Infections (CROI). March 2024. 4 Taiwo, et al. Safety and Efficacy of VRC07-523LS plus Long-Acting Cabotegravir in the Phase 2 ACTG A5357 Trial. Presented at 31st Conference on Retroviruses and Opportunistic Infections (CROI). March 2024. 5 Rana, et al. Long-acting Injectable CAB/RPV is Superior to Oral ART in PWH with adherence challenges: ACTG A5359. Presented at 31st Conference on Retroviruses and Opportunistic Infections (CROI). March 2024. 6 Kamya, et al. SEARCH Randomized trial of Dynamic Choice HIV Prevention including injectable cabotegravir (CAB-LA). Presented at 31st Conference on Retroviruses and Opportunistic Infections (CROI). March 2024. 7 Hsu, et al. Real-World Effectiveness of Cabotegravir + Rilpivirine vs. Standard of Care Oral Regimens in the US. Presented at 31 Conference on Retroviruses and Opportunistic Infections (CROI). March 2024. 8 Sörstedt, et al. Switching to DTG+3TC vs 3-drug regimens in routine clinical care: long-term Swedish data. Presented at 31st Conference on Retroviruses and Opportunistic Infections (CROI). March 2024. 9 Data on File

Phase 2Phase 1Clinical ResultPhase 3

06 Nov 2023

·www.prnewswire.com

HALOZYME REPORTS THIRD QUARTER 2023 FINANCIAL AND OPERATING RESULTS

Royalty Revenue Increased 15% YOY to Record $114.4 million Announces Acceleration into 2023 of Remaining $250M Share Repurchase through ASR GAAP Diluted EPS of $0.61 and Non-GAAP Diluted EPS of $0.751 Maintained Revenue Guidance and Raised 2023 EBITDA Guidance to $430-$445 million and Non-GAAP EPS Guidance to $2.70-$2.80 SAN DIEGO, Nov. 6, 2023 /PRNewswire/ -- Halozyme Therapeutics, Inc. (NASDAQ: HALO) ("Halozyme" or the "Company") today reported its financial and operating results for the third quarter ended September 30, 2023 and provided an update on its recent corporate activities and outlook. "I am delighted that our strong operating performance and expense management throughout the year have resulted in an increase to EBITDA and non-GAAP EPS guidance. Today, we also announced an acceleration into this year of the remaining $250 million under the current approved $750 million share repurchase plan, authorized in 2021. This action is part of our disciplined and balanced approach to capital allocation and reflects our assessment that share repurchases today are a strong return on investment opportunity," said Helen Torley, president and CEO of Halozyme. "Supporting our conviction in long-term revenue growth and durability, the third quarter was remarkable, with multiple, meaningful, de-risking events and progress for our upcoming series of Wave 3 potential product launches, projected for 2023-2025. I am also pleased with the progress in the quarter in advancing discussions on development of our HVAI." Recent Corporate Highlights: Announced an acceleration, into this year, of the remaining $250 million under the current approved $750 million share repurchase plan authorized in 2021. The Company intends to execute the $250 million share repurchase by entering into an accelerated share repurchase ("ASR") transaction with a financial Institution, immediately, subject to market conditions. In August 2023, the Company announced positive results of a clinical study with its high-volume auto-injector demonstrating SC administration of 10 mL of a representative biologic product co-formulated with our ENHANZE® drug delivery technology in approximately 30 seconds. The results were presented at the 13th annual Partnership Opportunities in Drug Delivery ("PODD") conference in October 2023. Recent Partner Highlights: In November 2023, Halozyme and Acumen entered into a global collaboration and non-exclusive license agreement that provides Acumen access to ENHANZE® technology for a single target. Acumen intends to explore the potential use of ENHANZE for ACU193, Acumen's clinical stage monoclonal antibody candidate to target Amyloid-β Oligomers for the treatment of early Alzheimer's disease. In October 2023, Bristol Myers Squibb reported positive topline results from the Phase 3 CheckMate-67T trial evaluating a SC formulation of Opdivo (nivolumab) with ENHANZE® in patients with advanced or metastatic clear cell renal cell carcinoma ("ccRCC") who have received prior systemic therapy. The study met its co-primary pharmacokinetics ("PK") endpoints and a key secondary endpoint. In September 2023, Chugai Pharmaceuticals, a member of the Roche Group, announced that it had obtained regulatory approval for Phesgo® from the Ministry of Health, Labour and Welfare ("MHLW") in Japan. Halozyme is entitled to receive royalties for Phesgo® sales in Japan under its agreement with Roche. In September 2023, argenx announced the Committee for Medicinal Products for Human Use ("CHMP") of the European Medicines Agency ("EMA") has recommended European Commission ("EC") approval of the SC injectable formulation of efgartigimod as an add on to standard therapy for the treatment of adult patients with generalized myasthenia gravis ("gMG") who are anti-acetylcholine receptor ("AChR") antibody positive. The EC is expected to make a decision on the argenx marketing authorization application within approximately 67 days following the CHMP recommendation. In September 2023, Zai Lab limited (argenx commercial partner for China) announced the Center for Drug Evaluation ("CDE") of the National Medical Products Administration ("NMPA") granted Breakthrough Therapy Designation for efgartigimod alfa injection (SC injection) (efgartigimod SC) for the treatment of patients with chronic inflammatory demyelinating polyneuropathy ("CIDP"). The Breakthrough Therapy Designation for efgartigimod SC was supported by data from both global and Chinese patients enrolled in the ADHERE study. In September 2023, Roche informed the Company that there will be a delay in the projected launch timing for Tecentriq® SC in the U.S. as a result of Roche's need to update chemistry, manufacturing, and controls ("CMC") processes for Tecentriq® SC. Roche expects these updates to be completed in 2023 to support a potential launch of Tecentriq® SC in the U.S. in 2024. There is no expected impact on ex-U.S. filings for Tecentriq® SC. In August 2023, Roche announced the approval of Tecentriq® SC with ENHANZE® by the Medicines and Healthcare products Regulatory Agency ("MHRA") in Great Britain, triggering an $8.0 million milestone payment to Halozyme and the right to receive royalties on net product sales. In August 2023, ViiV initiated a Phase 2b study to evaluate the efficacy, safety, PK and tolerability of VH3810109 (N6LS) administered subcutaneously with ENHANZE® in combination with cabotegravir. In August 2023, ViiV achieved a development milestone, which triggered a $5 million milestone payment to Halozyme. In July 2023, argenx reported positive data from the ADHERE study evaluating VYVGART® Hytrulo with ENHANZE® in adults with CIDP. The study met its primary endpoint resulting in a 61% reduction in risk of relapse compared to placebo. In July 2023, Roche announced that the Phase III OCARINA II trial evaluating OCREVUS® (ocrelizumab) with ENHANZE® as a twice a year 10-minute SC injection met its primary and secondary endpoints in patients with relapsing forms of multiple sclerosis ("MS") or primary progressive MS ("RMS" or "PPMS"). Third Quarter 2023 Financial Highlights: Revenue was $216.0 million compared to $209.0 million in the third quarter of 2022. The 3% year-over-year increase was driven by growth in ENHANZE® revenue streams with an increase in royalty revenue and an increase in product sales as a result of an increase in bulk rHuPH20 sales driven by partner demand and continued growth in XYOSTED®, partially offset by in the timing of milestone revenue. Revenue for the quarter included $114.4 million in royalties, an increase of 15% compared to $99.6 million in the prior year period, primarily attributable to increases in revenue of subcutaneous DARZALEX® (daratumumab) and Phesgo®. Cost of sales was $54.8 million, compared to $47.3 million in the third quarter of 2022. The increase was driven by growth in proprietary product sales and bulk rHuPH20 demand. Amortization of intangibles expense was $20.3 million, compared to $27.2 million in the third quarter of 2022. The decrease was due to a remeasurement period adjustment of our acquired intangible assets recorded in the fourth quarter of 2022, partially offset by an impairment charge of $2.5 million to fully impair the TLANDO® product rights intangible asset as a result of the license agreement termination notice provided to Lipocine in September 2023. Research and development expense was $17.3 million, compared to $16.7 million in the third quarter of 2022. Selling, general and administrative expense was $35.3 million, compared to $34.5 million in the third quarter of 2022. The increases were primarily due to an increase in compensation expense. Operating income was $88.3 million, compared to operating income of $83.3 million in the third quarter of 2022. Net Income was $81.8 million, compared with net income of $61.6 million in the third quarter of 2022. EBITDA was $124.6 million, compared with EBITDA of $109.8 million in the third quarter of 2022. Adjusted EBITDA was $114.9 million, compared with Adjusted EBITDA of $110.2 million in the third quarter of 2022.1 Earnings per Share: GAAP diluted earnings per share was $0.61, compared with $0.44 in the third quarter of 2022. Non-GAAP diluted earnings per share was $0.75, compared with $0.74 in the third quarter of 2022.1 Cash, cash equivalents and marketable securities were $483.3 million on September 30, 2023, compared to $362.8 million on December 31, 2022. The increase was primarily due to the cash provided by operating activities, partially offset by repurchase of common stock for $150.0 million in the first quarter of 2023. Financial Outlook for 2023 The Company is raising its EBITDA and non-GAAP EPS guidance ranges to reflect strong expense management. For the full year 2023, the Company now expects: Total revenue of $825 million to $845 million, representing growth of 25% to 28% over 2022 total revenue primarily driven by continued strength in Wave 2 products, including DARZALEX® SC and Phesgo® utilizing ENHANZE®, as well as full year auto-injector royalty and product contribution. The Company expects revenue from royalties of $445 million to $455 million, representing growth of 23% to 26%. EBITDA of $430 million to $445 million, representing growth of >30% over 2022. EBITDA excludes the impact of amortization costs related to the Antares Pharma acquisition.1 Non-GAAP diluted earnings per share of $2.70 to $2.80, representing growth of 22% over 20221. The Company's earnings per share guidance does not consider the impact of potential future share repurchases. Table 1. 2023 Financial Guidance Webcast and Conference Call Halozyme will host its Quarterly Update Conference Call for the third quarter ended September 30, 2023 today, Monday, November 6, 2023 at 1:30 p.m. PT/4:30 p.m. ET. The conference call may be accessed live with pre-registration via link: . The call will also be webcast live through the "Investors" section of Halozyme's corporate website and a recording will be made available following the close of the call. To access the webcast and additional documents related to the call, please visit Halozyme.com. About Halozyme Halozyme is a biopharmaceutical company bringing disruptive solutions to significantly improve patient experiences and outcomes for emerging and established therapies. As the innovators of the ENHANZE® technology with the proprietary enzyme rHuPH20, Halozyme's commercially-validated solution is used to facilitate the delivery of injected drugs and fluids in order to reduce the treatment burden to patients. Having touched more than 700,000 patient lives in post-marketing use in seven commercialized products across more than 100 global markets, Halozyme has licensed its ENHANZE® technology to leading pharmaceutical and biotechnology companies including Roche, Takeda, Pfizer, AbbVie, Eli Lilly, Bristol-Myers Squibb, Alexion, argenx, Horizon Therapeutics, ViiV Healthcare, Chugai Pharmaceutical and Acumen Pharmaceuticals. Halozyme also develops, manufactures and commercializes, for itself or with partners, drug-device combination products using its advanced auto-injector technology that are designed to provide commercial or functional advantages such as improved convenience and tolerability, and enhanced patient comfort and adherence. The Company has a commercial portfolio of proprietary products including XYOSTED® and TLANDO® and partnered commercial products and ongoing product development programs with several pharmaceutical companies including Teva Pharmaceuticals and Idorsia Pharmaceuticals. Halozyme is headquartered in San Diego, CA and has offices in Ewing, NJ and Minnetonka, MN. Minnetonka is also the site of its operations facility. For more information visit and connect with us on LinkedIn and Twitter. Note Regarding Use of Non-GAAP Financial Measures In addition to disclosing financial measures prepared in accordance with U.S. generally accepted accounting principles ("GAAP"), this press release and the accompanying tables contain certain non-GAAP financial measures. The Company reports earnings before interest, taxes, depreciation, and amortization ("EBITDA"), adjusted EBITDA and Non-GAAP diluted earnings per share, and guidance with respect to those measures, in addition to, and not as a substitute for, or superior to, financial measures calculated in accordance with GAAP. The Company calculates non-GAAP diluted earnings per share excluding share-based compensation expense, amortization of debt discount, intangible asset amortization, transaction costs for business combinations, realized gains or losses on marketable security sales and certain adjustments to income tax expense. The Company calculates EBITDA excluding interest, taxes, depreciation and amortization. The Company calculates adjusted EBITDA excluding transaction costs for business combinations. Reconciliations between GAAP and Non-GAAP financial measures are included at the end of this press release. The Company does not provide reconciliations of forward-looking adjusted measures to GAAP due to the inherent difficulty in forecasting and quantifying certain amounts that are necessary for such reconciliation, including adjustments that could be made for changes in contingent liabilities, share-based compensation expense and the effects of any discrete income tax items. The Company evaluates other items of income and expense on an individual basis for potential inclusion in the calculation of Non-GAAP financial measures and considers both the quantitative and qualitative aspects of the item, including (i) its size and nature, (ii) whether or not it relates to the Company's ongoing business operations and (iii) whether or not the Company expects it to occur as part of the Company's normal business on a regular basis. Non-GAAP financial measures do not have any standardized meaning and are therefore unlikely to be comparable to similarly titled measures presented by other companies. These non-GAAP financial measures are not meant to be considered in isolation and should be read in conjunction with the Company's consolidated financial statements prepared in accordance with GAAP; and are not prepared under any comprehensive set of accounting rules or principles. In addition, from time to time in the future there may be other items that the Company may exclude for purposes of its non-GAAP financial measures; and the Company may in the future cease to exclude items that it has historically excluded for purposes of its non-GAAP financial measures. The Company considers these non-GAAP financial measures to be important because they provide useful measures of the operating performance of the Company, exclusive of factors that do not directly affect what the Company considers to be its core operating performance, as well as unusual events. The non-GAAP measures also allow investors and analysts to make additional comparisons of the operating activities of the Company's core business over time and with respect to other companies, as well as assessing trends and future expectations. The Company uses non-GAAP financial information in assessing what it believes is a meaningful and comparable set of financial performance measures to evaluate operating trends, as well as in establishing portions of our performance-based incentive compensation programs. Safe Harbor Statement In addition to historical information, the statements set forth in this press release include forward-looking statements including, without limitation, statements concerning the Company's financial performance (including the Company's financial outlook for 2023) and expectations for future growth, achieving operational goals, profitability, return on investment, revenues (including royalty, milestone and product sales revenue), EBITDA, non-GAAP diluted earnings-per-share and potential share repurchase under its share repurchase program. Forward-looking statements regarding the Company's ENHANZE® drug delivery technology may include the possible benefits and attributes of ENHANZE®, its potential application to aid in the dispersion and absorption of other injected therapeutic drugs and facilitating more rapid delivery and administration of higher volumes of injectable medications through subcutaneous delivery. Forward-looking statements regarding the Company's business may include potential growth and receipt of royalty and milestone payments driven by our partners' development and commercialization efforts, potential new clinical trial study starts and clinical data, regulatory submissions and product launches, the size and growth prospects of our partners' drug franchises, potential new or expanded collaborations and collaborative targets and regulatory review and potential approvals of new partnered or proprietary products and the Company's development and partnership potential of a high volume auto-injector. These forward-looking statements are typically, but not always, identified through use of the words "believe," "enable," "may," "will," "could," "intends," "estimate," "anticipate," "plan," "predict," "probable," "potential," "possible," "should," "continue," and other words of similar meaning and involve risk and uncertainties that could cause actual results to differ materially from those in the forward-looking statements. Actual results could differ materially from the expectations contained in these forward-looking statements as a result of several factors, including unexpected levels of revenues, expenditures and costs, unexpected delays in the execution of the Company's share repurchase program, unexpected results or delays in the growth of the Company's business, or in the development, regulatory review or commercialization of the Company's partnered or proprietary products (including its high volume auto-injector), regulatory approval requirements, unexpected adverse events or patient outcomes and competitive conditions. These and other factors that may result in differences are discussed in greater detail in the Company's most recent Annual Report on Form 10-K and Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission. Except as required by law, the Company undertakes no duty to update forward-looking statements to reflect events after the date of this release. Contacts: Tram Bui VP, Investor Relations and Corporate Communications 609-359-3016 [email protected] Dawn Schottlandt Argot Partners 212-600-1902 [email protected] Footnotes: 1. Reconciliations between GAAP reported and non-GAAP financial information and adjusted guidance measures are provided at the end. SOURCE Halozyme Therapeutics, Inc.

Phase 3License out/inClinical ResultDrug ApprovalBreakthrough Therapy

28 Sep 2023

·www.fiercepharma.com

GSK dials up HIV sales projection to £7B by 2026, updates next-gen launch timelines

GSK's ViiV Healthcare aims to have an ultra-long-acting HIV regimen on the market by 2027 and a self-administered option available by 2030. Riding on the growth of long-acting antiretroviral therapy Cabenuva, GSK is laying out a more optimistic vision for its overall HIV business. GSK projects its HIV products will reach £7 billion ($8.5 billion) in sales by 2026, Deborah Waterhouse, CEO of GSK’s specialist HIV company ViiV Healthcare, said Thursday. The British pharma company expects the HIV franchise will grow sales by an average of 6% to 8% annually during the five years leading up to 2026. That was a step up from the mid-single-digit percentage annual growth target that GSK laid out for ViiV back in 2021. Last year, GSK recorded £5.7 billion in HIV drug sales, a 12% increase from 2021 at constant currencies. While the £7 billion forecast is new from GSK itself, the number was already raised by ODDO BHF analysts last year. Strong performance of long-acting HIV regimen Cabenuva fueled the new guidance, Waterhouse told reporters during a press call. Approved by the FDA in January 2021, Cabenuva can be given every one or two months. In the first half of 2023, the drug brought in £303 million. Cabenuva is doing well because long-acting drugs—compared with traditional daily orals—give patients a level of freedom so they don’t fear missing daily doses, Waterhouse said. The long-acting regimens will make up about a third of GSK’s HIV revenue by 2026, Waterhouse said. They will help GSK when its older-generation dolutegravir (Tivicay) loses patent protection toward the end of the decade. Dolutegravir’s core composition patent expires in April 2028 in the U.S., while its formulation patents related to the combination therapies Dovato and Juluca expire in 2029 and 2030, respectively, according to Waterhouse. Still, daily pills such as Gilead Sciences’ megablockbuster Biktarvy remain the mainstay of HIV treatment. Waterhouse has previously acknowledged that for some patients, having to go to a clinic every two months to receive Cabenuva can be too cumbersome. That’s why GSK has been working to develop ultra-long-acting drugs and self-administered options. The company on Thursday provided new estimates as to when it expects to bring such products to the market. GSK aims to select a lead self-administered long-acting HIV candidate next year and hopes to win an approval by 2030. In addition, the company plans to incorporate cabotegravir—a component in Cabenuva—into a once-every-four-month treatment by 2027, with a goal to further extend the dosing interval to twice yearly by 2030. The new timeline for the self-administered product marks a delay from GSK’s original plan, shared in 2021. The self-administered version takes longer to develop because GSK needs to find a proper device to deliver the drug, ViiV’s R&D chief Kimberly Smith, M.D., told Fierce Pharma during an interview. For this therapy, GSK is initially targeting a dosing interval of around two to three months, she said. Three factors will determine which regimen GSK will advance, Smith said. Besides sufficient dosing interval and tolerability, the drug must come in the right volume to fit into an autoinjector. GSK has several options to choose from. Besides reformulating cabotegravir, the company has a Shionogi-partnered third-generation integrase inhibitor coded VH184, which also has long-acting potential and the ability to tackle multiple HIV mutations, plus a newer integrase inhibitor called VH310. “We do believe that the regimen should be built on a foundation of integrase inhibitors,” Smith said during the press call. GSK’s approach to long-acting regimens is different from rival Gilead’s. Gilead has Sunlenca, a capsid inhibitor that can be given every six months. The drug is approved to be used in combination with other therapies to treat patients whose HIV isn’t controlled by existing treatments. GSK is stressing the importance of integrase inhibitors not because it happens to have several options in the class, but also because they have shown a high barrier to resistance compared with available capsid inhibitors, Smith explained to Fierce Pharma. As for the ultra-long-acting treatments, GSK has set cabotegravir as one of the components but has yet to determine the final regimen. Smith mentioned N6LS, a broadly neutralizing antibody that GSK licensed from the NIH, as a potential combination partner. The drug entered phase 2b testing in August, and GSK is exploring using its partner Halozyme’s drug delivery technology to make it a subcutaneous formulation. Smith suggested that the self-administered and ultra-long-acting therapies might target different patient populations. The dosing interval for ultra-long-acting matches the frequency a patient typically visits the clinic to monitor the disease. Combining the two together allows the doctor to directly observe treatment. By comparison, the self-administered version could appeal to people who are comfortable having their drugs in their house. Eventually, the longer the interval of the clinic-administered drug, the higher the bar for the self-administered version, Smith argued. “If you’ve only got to come into the clinic three times a year, do you want the hassle of having it at home?” Smith said. “It’s got to be a really well-tolerated, easy-to-deliver regimen.”

Drug ApprovalPhase 2

100 Deals associated with GSK-3810109

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
HIV Infections	Phase 2	US	ViiV Healthcare Ltd.	22 Jun 2021
HIV Infections	Phase 2	US	National Institute of Allergy & Infectious Diseases	22 Jun 2021
HIV Infections	Phase 2	US	Halozyme Therapeutics, Inc.	22 Jun 2021
HIV Infections	Phase 2	AR	ViiV Healthcare Ltd.	22 Jun 2021
HIV Infections	Phase 2	BR	ViiV Healthcare Ltd.	22 Jun 2021
HIV Infections	Phase 2	CA	ViiV Healthcare Ltd.	22 Jun 2021
HIV Infections	Phase 2	MX	ViiV Healthcare Ltd.	22 Jun 2021
HIV Infections	Phase 2	PE	ViiV Healthcare Ltd.	22 Jun 2021

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04871113 (CTgov)	Phase 2	HIV Infections	63	GSK3810109A (Part 1:GSK3810109A 40milligram(mg)/Kilogram Intravenously (IV))	qjtmvudhek(bzhluccmje) = xkcacnxlif yaiamuawus (bbciuvemtk, tsjvloilmq - hnekzmbgqf) View more	-	18 Nov 2023
				GSK3810109A (Part 1: GSK3810109A 280 mg IV)	qjtmvudhek(bzhluccmje) = vnpcfzjrlf yaiamuawus (bbciuvemtk, afwehsbvrp - qkwujhtnok) View more
NCT03538626 (CTgov)	Phase 1	HIV Infections	33	VRC-HIVMAB091-00-AB (Group 1: N6LS (5 mg/kg IV) Single Dose)	ekagknzywu(firsrwgpdq) = qvwhmswton gehauwpyco (utefasgapx, ipwyllragv - yeanssilvu) View more	-	21 Sep 2023
				VRC-HIVMAB091-00-AB (Group 2: N6LS (5 mg/kg SC) Single Dose)	ekagknzywu(firsrwgpdq) = kztreymrjf gehauwpyco (utefasgapx, wlsvuuoomy - otisfghgeq) View more

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GSK-3810109

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