Biggest unpartnered assets: Argenx nears crunch time

There are two ways to look at highly valued biotech assets that have not been licensed to a big partner: they are either underappreciated gems or a result of investors’ most unrealistic expectations. With a Pdufa date in December Argenx could soon see into which category efgartigimod, a regular in Evaluate Vantage’s analyses of these unpartnered assets, falls.

While efgartigimod has topped this year’s analysis, the data show why so often big pharma is right to steer well clear of certain biotech projects. Cortexyme’s atuzaginstat would have made the shortlist had it not bombed in the clinic last month, for instance, while Iovance’s TIL therapies are still in play – just – though major questions now hang over their approvability.

The analysis looks only at projects in the hands of biotechs with market caps below $30bn that are not subject to major company deals, beyond clinical trial collaborations or small, regional tie-ups. Project NPVs are computed from Evaluate Pharma’s consensus of sellside revenue forecasts.

Action date

Efgartigimod, which claimed the runner-up and top spots, respectively, the last two times this analysis was carried out, faces a December 17 Pdufa date for myasthenia gravis; while approval is widely expected, a few analysts have been reining in expectations for this FcRn-targeting class. On a consensus basis, however, forecast 2026 efgartigimod sales are $2.9bn, remarkably around $300m higher than a year ago.

One hope might be that US approval could trigger a lucrative licensing deal. True, Argenx has long insisted that it wants to go it alone with efgartigimod, a fact that no doubt contributes to the project's unpartnered status. But there is no denying that every asset has its price, and if a big enough deal came along Argenx would undoubtedly jump at the chance.

Several other assets in this year’s analysis are also approaching binary catalysts that could spur licensing or, alternatively, prove potential partners’ reluctance correct.

Allakos’s anti-siglec 8 MAb lirentelimab, for instance, will in late 2021/early 2022 generate phase 3 data from studies in eosinophilic gastritis, duodenitis and oesophagitis. It appears in fifth place, with an NPV 40% above Allakos’s market cap.

Meanwhile, US regulatory decisions loom for Reata’s bardoxolone in Alport syndrome (February 25 action date) and TG Therapeutics’ combo of ublituximab plus the recently approved umbralisib in CLL (March 25). The TG assets carry a combined NPV of $9.1bn, according to Evaluate Pharma, but two thirds of this relates to ublituximab monotherapy, the investment case for which hinges on use in multiple sclerosis.

Bardoxolone’s development path has been convoluted, involving a since dissolved tie-up with Abbvie for a broader indication. Filing for Alport had been delayed by an FDA request for longer-term data, and approval is by no means assured.

If such doubts are keeping potential partners away then a similar issue could be at play with Iovance’s lifileucel, whose latest delay raises important questions about the approvability of TIL therapies. Before this setback sellside forecasts for this and Iovance’s other TIL project, LN-145, had yielded a combined NPV of $10.4bn.

Some will point to Cortexyme’s atuzaginstat and Apellis’s intravitreal pegcetacoplan as canaries in the coalmine for unpartnered and overvalued biotech projects. Atuzaginstat flopped in an Alzheimer’s trial, before which it had carried a $6.2bn NPV and would have appeared sixth in this analysis. Before Apellis’s geographic atrophy disappointment pegcetacoplan had been valued at $3.8bn.

Other unpartnered assets that still have much to prove include Mirati’s adagrasib, Turning Point’s repotrectinib, and the cell therapies obe-cel (from Autolus) and FT516 (Fate).

On the other hand, Autolus has shown that an industry partner is not always a pressing need. A deal with Blackstone has allowed it to monetise obe-cel and fund more promising pipeline assets.