Parabilis Medicines (PBLS) investor relations material

Platform innovation and scientific rationale

• Helicon platform enables targeting of previously undruggable intracellular proteins by using stabilized helical peptides, expanding druggable space beyond small molecules and antibodies.

• Over 2,000 amino acids are used to create diverse peptides, allowing prediction and engagement of intracellular targets.

• Zolucatetide is the first clinical test of the platform, showing ability to reach and inhibit intracellular targets.

Clinical progress and data highlights

• Zolucatetide demonstrated a 74% response rate in 38 desmoid tumor patients, with median treatment time of nine months.

• Safety profile is favorable, with minor bone effects at high doses and no new safety signals observed.

• Phase III trial for desmoid tumors is planned for the first half of 2027, with dose and schedule optimization ongoing.

• Endpoints under discussion with FDA include ORR and PFS, with a preference for a dual endpoint to expedite readout.

Indication expansion and pipeline strategy

• Zolucatetide is being developed for desmoid tumors, FAP, ACP, HCC, and colorectal cancer, with tumor-agnostic studies planned.

• In FAP, dramatic reductions in polyp burden have been observed, with dedicated cohort data expected in Q1 and further expansion through 2027.

• ACP patients showed significant tumor reduction and improved symptoms in early data, with further recruitment prioritized.

• HCC and CRC are being explored, with HCC data expected in the first half of next year and CRC combinations under development.