Bristol exit clips Dragonfly’s wings

When Bristol Myers Squibb licensed Dragonfly’s IL-12 project DF6002 for $475m in “near-term up-fronts” it showed big pharma’s continued interest in cytokines despite several disappointments in the field. Now Bristol has clearly seen enough, handing back rights to Dragonfly yesterday. It is not the only large group to have exited the arena. Perhaps most notably, Astrazeneca’s website notes that MEDI1191 has been discontinued for efficacy/safety reasons, although its partner Moderna still lists the project in its pipeline. And last month Merck KGaA offloaded M9241 to PDS Biotechnology for $5m up front; the latter has been studying the project alongside its HPV16-targeting cancer vaccine PDS0101, and plans a registrational trial. Since the last time Evaluate Vantage looked at the space, the IL-12 dream has soured for smaller players, too: Rubius’s RTX-224 has fallen by the wayside, Alaunos (formerly Ziopharm) has gone quiet on Ad-RTS-hIL-12, and the prospects for Inovio’s INO-9012 look bleak after a recent restructuring. Astra is still involved in IL-12, through the gene therapy MEDI9253. Another gene therapy, Oncosec’s Tavo, is the most advanced IL-12 asset, although a recent cut of the Keynote-695 trial showed a dwindling response rate compared with earlier readouts.

Oncology projects working on IL-12 signalling
Project Company Class Clinical trial
Phase 2
Tavo Oncosec Electroporation-delivered IL-12 gene therapy Keynote-695 (Keytruda combo) in melanoma: latest cut in Nov 2022 showed 19% ORR in 101 pts; topline primary endpoint results due Q1 2023
GEN-1 Imunon (previously known as Celsion) IL-12 gene therapy Ovation-2 in ovarian cancer
M9241 (PDS0301) PDS Biotech/Merck KGaA IL-12/Ab fusion protein Various trials ongoing sponsored by NCI; incl NCT04287868 of PDS0101 + M924 + bintrafusp alfa
Phase 1/2
DF6002 Dragonfly (Bristol handed back rights Feb 2023) Monovalent IL-12 Fc fusion protein Dose escalation +/- Opdivo in solid tumours
INO-9012 Inovio Plasmid encoding IL-12 subunit proteins + INO-5401 & Libtayo in glioblastoma; & Tecentriq in urothelial carcinoma
Phase 1
MEDI9253 Astrazeneca   IL-12 gene therapy Imfinzi combo in solid tumours
JCAR020 Bristol (ex Celgene/Juno) IL-12 secreting anti-Muc16 Car-T Muc16-positive tumours*
WTX-330 Werewolf Therapeutics Conditionally-activated IL-12 prodrug Monotherapy in solid tumours/non-Hodgkin lymphoma
XTX301 Xilio Tumour-activated IL-12 Monotherapy in solid tumours
*Investigator sponsored study. Source: Evaluate Pharma &

The table in this story has been updated to include WTX-330 and XTX301.

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