Our progress towards a functional cure for HIV.

Our Progress

We believe that people living with HIV have the potential to fight the virus, but they need a boost to win the war.

Thatโ€™s why weโ€™re pioneering a functional cure that amplifies the strength of the human immune system.โ€‹

A young couple embracing each other

Phase 1a Design

What we set out to learn

First, we conducted a Phase 1a clinical study that evaluated the safety and feasibility of AGT103-T in seven people living with HIV. We also sought to evaluate the durability of the modified cells.

The participants received AGT103-T modified cells via infusion, followed by up to 180 days of monitoring post infusion for potential adverse events.

01
  • 1. Participant Screening
  • 2. Leukapheresis
02

Cell Manufacturing & QC Testing

03

Infusion

04

180-Day post-infusion follow up

Phase 1a Findings

What we observed

The Phase Ia data was encouraging across all three areas of evaluation:

  1. We observed no serious adverse events.
  2. The modified CD4 T cells were engrafted and persisted in all participants
  3. The CD4 T cells maintained their functionality

Notably, we also observed a consistent expansion of the CD4 T cells in patients that peaked approximately 14-days post infusion, an unexpected response that gave us key insight into how best to design the next trial protocol.

  • a. The clinic failed to draw blood from 02-001 for research samples on the Day 180.โ€‹
  • b. Additional data unavailable at time of publication, see follow-on ATI study for additional detail.
  • c. Day 90 sample for 02-009 arrived clotted and could not be processed.

Follow-on ATI Design

Building on our findings

Following the Phase Ia study, we explored how the engrafted cells might impact their response to an analytic treatment interruption.

To do so, we designed a follow-on study with six participants from the Phase Ia trial. This new study featured an analytical treatment interruption (ATI) where we took the participants off of their antiretroviral therapy (ART) and evaluated their immune response to the virus.

01
  • Baseline criteria:
  • VL undetectable
  • CD4 counts normal
  • No infections
02

Cease NNRTI for seven days then all other drugs

03

Follow Viral Load and CD4 Count

04

Re-commence at any time or if VL > 100K X2 or CD4 < 350

HIV and the Immune System

What we would expect

Typically, when well-controlled HIV patients on ART go off their medication we see:

  • Viremia (the detectable amount of HIV within the patient) increases and then comes to a set point that on average is around 50K-100K copies/ml
  • CD4 count goes down
  • CD8 T cell count stays flat

Follow-on ATI Findings

What we observed

What we saw in all six study participants was quite unexpected. CD8 cell count increased after the viral rebound and CD4 cell count remained generally stable.

Following the first ATI, participants were put back on ART and were offered to go through a second ATI.

The reason for the second ATI was to see if the immune system would respond more effectively now that the cells had been exposed to the virus.

HIV VL after ART Restart

HIV VL

CD4 Count

CD8 Count

Participants

Participant ID Days Between Infusion and ATI Start
01-008 150
02-009 99
01-002 490
02-001 246
01-005 411
01-007 390

Impact of Multiple ATIs

The potential of autovaccination

Four out of the six participants agreed to the second ATI. In all four participants we saw:

  • Consistent CD8 and CD4 responses to the first ATI
  • A significant reduction in peak viremia compared to the first ATI
  • Set points that were all between 7,000 and 20,000 cp/mL

Participants

Participant ID Days Between Infusion and ATI Start
01-008 150
02-009 99
01-002 490
02-001 246

Our Takeaways

Together, our data provides key insights that are informing our next clinical study to maximize the ATI protocol, enabling us to evaluate AGT103-Tโ€™s potential to impact the systemic immune response.