Prime Medicine (PRME) Jefferies 2024 Global Healthcare Conference summary

Company overview and technology

• Next-generation gene editing platform enables precise gene correction, not just inactivation, with broad disease applicability.

• Prime editing achieves high efficacy (>90% in lead program) and demonstrates a superior safety profile with minimal off-target effects.

• Technology can address single-base mismatches, small insertions/deletions, and larger DNA segments, including hotspot and PASSIGE editing.

• Prime editing avoids double-strand breaks, reducing risks compared to CRISPR and base editing.

• Field is seen as having three main generations: CRISPR (knockdown), base editing (limited correction), and prime editing (broad correction).

Lead program (PM359) and clinical trial plans

• IND for PM359 in chronic granulomatous disease (CGD) was approved in 27 days with minimal FDA queries.

• First patient dosing expected about six months post-IND due to site activation, patient consent, and cell processing timelines.

• Initial cohort will enroll 2-3 stable adult CGD patients, then expand to adolescents and children; screen failure rate expected to be near zero.

• International, multi-site study planned, with expansion to Europe and the Americas; rapid progression to pivotal trial is a goal.

• Regulatory agencies require sequential dosing and safety review before enrolling additional patients.

Clinical endpoints and regulatory strategy

• Key outcomes: safety, engraftment of edited cells, and DHR assay to measure correction of enzymatic defect.

• Targeting >15-20% positive neutrophils in DHR assay, a threshold discussed with FDA and other agencies.

• Frequency of infections is variable and difficult to quantify; improvement in infection and inflammation will be monitored.

• Less than 20 patients may be sufficient for accelerated approval if data are dramatic, with safety as a primary focus.