Agenus looks to new deals and an ex-US path

After two regulatory rebuffs and, as of yesterday, two bust licensing deals, Agenus faces some tough choices. Rather than throwing in the towel, the group has moved to talking up alternative ways of getting to market with the bot-bal combo the FDA threw out last month, as well as finding new partners for the two assets recently handed back by former licensees.

However, Agenus won’t find the going easy, and its latest suggestion for a phase 3 bot-bal study is nebulous and looks like another attempt at a short cut to approval. And squeezing out economics from new partners – if any can be found – will be complicated by a separate licensing transaction that, it has emerged, hasn’t been extinguished.

That transaction was signed with Ligand Pharmaceuticals in May, and brought in $75m to help Agenus fund bot-bal (a combo of the anti-CTLA-4 MAb botensilimab and anti-PD-1 MAb balstilimab). In return Agenus gave up 32% of the milestones and 19% of the royalties due on six partnered assets, including the anti-TIGIT x CD96 MAb AGEN1777 and the 4-1BB agonist MAb AGEN2373.

These two assets are now in focus because Bristol Myers Squibb has given notice to end a deal covering the former, while Gilead has declined to opt into the latter, it emerged yesterday, and Agenus is trying to license them out again. And a May SEC filing suggested that the Ligand obligation related only to payments “by and between [Agenus] and Bristol ... and [Agenus] and Gilead”.

However, this is not the case: any future milestones or royalties from new partners “would also fall under the Ligand deal”, Agenus told ApexOnco. Any financial benefit Agenus might accrue from a new licensee would thus be hampered by this ongoing mortgage.

“Certain groups”

As for bot-bal, Agenus yesterday claimed to have been “approached by certain groups”, including one proposing to run a randomised phase 3 trial “for as little as $10m”. Such a study could enrol within a year, such rapidity being due to the patient demand that's been generated, its chief executive, Garo Armen, told investors on a second-quarter financials call.

Armen also claimed to have had “initial interaction with a major agency whose stance is diametrically opposite to the FDA”, which has now rejected balstilimab not once but twice. Any hard facts have yet to emerge, however.

Until the first balstilimab setback Agenus appeared to be turning a corner at last, having burned through over $1bn of investor cash with little to show for it since being founded in 1994. Increasingly lucrative deals were struck, including with Incyte, Gilead and Bristol, the last netting Agenus $200m – its biggest ever licensing windfall.

However, the only remaining deals Agenus now has are with Merck & Co and UroGen – both also mortgaged to Ligand. The Incyte partnership is technically still in place, but none of the four projects involved is in active development. The Gilead deal also included a full license to a separate Agenus molecule, dalutrafusp alfa, but this too is now discontinued.

Including the Ligand proceeds Agenus had $94m in the bank at the half year, and is capitalised at only $110m.

Selected Agenus pipeline projects

Notes: *2.625% royalty; **31.875% of eligible milestones plus 18.75% of eligible royalties. Source: SEC filing & OncologyPipeline.