HIV competitive landscape (1)

MERCK

HIV Pipeline Strategy

• Merck’s near-term pipeline, including both treatment and prevention, is anchored by NRTTIs, underscoring their aspiration to be “first in class and best in class.” With four NDAs expected over the next few years, pipeline NRTTIs were positioned as potent and long-acting, appropriate for weekly and monthly dosing, with longer durations also possible.

Treatment

• All near-term treatment candidates are anchored by ISL and said to have favorable efficacy, safety, and drug-drug interaction profiles; which are especially important in older individuals and those with comorbidities.
  • Regimens noted as being INSTI-free, “reserving this important class of therapy for later, if needed.”
• DOR/ISL
  • Management reiterated that a NDA in VS individuals was recently submitted for this single-tablet, daily oral regimen, with a PDUFA date of April 28, 2026.
    • Filing in Japan was also confirmed.
  • Week 48 data from the Ph3 Protocol 053 trial (MK-8591A-053), investigating DOR/ISL in TN adults, will support an initial EMA application and US label expansion. PCD is currently estimated for October 19, 2025.Data is expected to be read out by the end of this year and presented in 2026.
  • Citing data presented at CROI 2025, DOR/ISL was positioned as non-inferior to INSTI-containing 3DRs, including B/F/TAF.
  • During the Q&A, management said DOR/ISL is expected to become a “preferred switch option” for the 1 in 5 HIV PWH switching treatments on an annual basis.
• ISL/LEN
  • Merck’s Ph3 partnership with Gilead is likely to be the first weekly oral to market.
    • The regimen was positioned as able to “address challenges around pill fatigue.”
  • Management discussed positive Ph2 data presented at IDWeek 2024, which supported advancement to Ph3.
  • The Ph3 ISLEND-1 and 2 trials were noted as completing recruitment ahead of schedule, with estimated PCDs in April 2026.
• ISL/ULO
  • Merck’s second weekly oral regimen was emphasized as being “wholly internal” and includes ulonivirine (ULO); an investigational NNRTI.
  • Called a “simplified regimen,” ISL/ULO is a single, small tablet (compared to ISL/LEN), which does not require a loading dose and has a favorable drug-drug interaction profile.
  • Ph1b data presented last week at IAS 2025 was shown, with management noting a Ph2b study (MK-8591B-060) in VS individuals is currently enrolling.
    • There are plans to investigate ISL/ULO in TN adults, but no specific timelines were provided.
  • When asked about differentiation from ISL/LEN during the Q&A, management called both options “terrific,” but reiterated ISL/ULO’s small tablet size, favorable drug-drug interaction profile, and TN indication.
    • However, it was said that the two weekly orals will be complementary, with ISL/LEN having the potency of ISL paired with the track record of LEN.

Prevention

• MK-8527
  • Merck’s only prevention asset in its near-term pipeline, MK-8527 is an NRTTI being developed as a monthly oral. It is not being investigated for treatment.
    • Positioned as a “discreet” option, it is a small tablet with no loading dose, which was said to start working within an hour with a 7-day forgiveness window.
  • Future messaging is likely to focus on convenience of long acting orals compared to injectables, which require in person appointments .
    • Management cited recent market research, which indicated that a third of individuals who would benefit from PrEP prefer a long-acting oral option.
    • During the Q&A, it was noted that the HIV testing requirement was still unknown, with management not speculating on future FDA requirements. However, it is likely to be in line with oral PrEP options, once every 3 months.
  • Ph2 data presented last week at IAS 2025 was shown, with management noting it supported monthly dosing at an 11 mg dose (which was determined to be the “sweet spot” for the different attributes that went into their modelling program).
  • MK-8527 will be investigated in two Ph3 trials, comparing efficacy and tolerability to FTC/TDF:
    • EXPrESSIVE-10 includes adolescent girls and young women across Kenya, South Africa, and Uganda, with enrollment set to begin in Fall 2025.
      • Women who become pregnant during the trial will be permitted to continue, in order to generate data in pregnancy and lactation.
      • This study is being conducted in partnership with the Gates Foundation.
    • EXPrESSIVE-11 includes all people at greater likelihood of HIV exposure across 16 countries, with enrollment set to begin in August 2025.
    • Further timelines were not provided, with management noting both trials are event-driven, with difficult-to-predict PCDs.
  • During the Q&A, an analyst noted one spontaneous abortion reported during the Ph2 trial (data presented at IAS 2025) and asked about the risk of including pregnant women in EXPrESSIVE-10. Management reiterated confidence in the full data set (both clinical and non-clinical), emphasizing that the study has been vetted through regulatory authorities.

Future Pipeline

• Management noted plans to investigate longer-acting options, with an HIV cure being Merck’s “ultimate ambition.”
  • The collaboration with Gilead to investigate an ISL prodrug injectable (MK-8239/GS1614) in combination with LEN, currently in Ph1, was the only future pipeline regimen mentioned.
• Merck’s cure strategy centers on eliminating the viral reservoir, with two approaches highlighted:
  • RT-TACK (Reverse Transcriptase-Targeted Activator of Cell Kill): NNRTIs with the added ability to selectively kill HIV-infected cells.
  • Disruptive new treatments that can eliminate virus-producing cells and reduce residual viremia.
• No specific details were provided on any cure assets or timelines, with management only noting they were currently evaluating assets in early development.

Corporate Messaging

• Emphasizing Merck’s history in HIV, including discovery of the first INSTI, management discussed wanting to be “part of the solution for the continued unmet need in HIV treatment and prevention worldwide.”
• During the presentation, management also highlighted a commitment to making an impact on the global epidemic, especially in areas with high rates of infection like sub-Saharan Africa.
  • Partnership with the Gates Foundation on the EXPrESSIVE-10 trial of MK-8527 was used to illustrate that commitment.
• When discussing the company’s near-term pipeline, Merck management also focused on the discreetness and convenience of LAOs.
  • Noting that 1/3 of individuals expressed a preference for LAOs, they were positioned as options that could overcome both pill-fatigue and injectable implementation challenges, lessening the need to attend regular clinic appointments.
  • Management also highlighted the emotional toll of being reminded of an HIV diagnosis on a daily basis.
• With a near-term treatment and prevention pipeline anchored by NRTTIs, Merck also messaged heavily on the extensive de-risking program followed in response to ISL’s CD4-depleting concerns and clinical hold.
  • The clinical program was said to have “the right models and the right clinical data,” giving the Merck confidence to continue the program.