Turning Point and Libtayo steal some pre-Asco thunder

On the eve of Asco two deals show that the current biotech market malaise might be focusing some chief executives’ minds.

Last year Turning Point’s valuation peaked at around $6.5bn. Also last year Sanofi’s chief executive, Paul Hudson, famously declared that Libtayo was in a position to challenge Merck & Co’s Keytruda in its most important use, front-line non-small cell lung cancer.

But the era of hype is over, to be replaced by a mood of austere reality: Turning Point was today snapped up by Bristol Myers Squibb for $4.1bn, a day after Sanofi ceded control of Libtayo to its partner Regeneron for just $900m up front. It seems that management teams are accepting the inevitable – something essential to ensuring that deals can still happen.

This is not to say that Bristol is necessarily getting a bargain with Turning Point, even at $4.1bn. The target company’s lead asset, repotrectinib, is vying for a slice of a small and apparently already competitive niche of the NSCLC market – Ros1-mutated disease.


Still, it is possible that recent repotrectinib data focused Bristol’s mind. In April Turning Point’s project showed remission data comparable with Roche’s marketed Ros1 drug Rozlytrek, but with suggestions of cross-trial superiority in terms of durability of those remissions.

Interestingly, Turning Point and Bristol both refer to repotrectinib as an anti-Ros1 and NTRK project – the same mechanistic attributes as Rozlytrek’s. They omit its activity at the related tyrosine kinase Alk, which early papers had cited as a mechanism, and which is the separate target of such approved drugs as Xalkori and Alecensa.

Instead, Turning Point’s pipeline boasts an early-stage pure Alk-targeting asset, TPX-0131, in phase 1. Whatever the reasons behind this subtle shift, Bristol is buying into not just repotrectinib but also Turning Point’s broader expertise in targeted cancer drugs, including assets against Met, Ret, Kras G12D and Claudin18.2 (through a recent deal with Lanova).

NSCLC therapy landscape for Alk & related mutations
Project AKA Company Target Status/study
Xalkori Crizotinib Pfizer Alk & Ros1 Approved for Alk+ or Ros1+
Zykadia Ceritinib Novartis Alk Approved for Alk+
Alecensa Alectinib Roche Alk Approved for Alk+
Alunbrig Brigatinib Takeda Alk Approved for Alk+
Lorbrena Lorlatinib Pfizer Alk Approved for Alk+
Rozlytrek Entrectinib/ RXDX-101 Roche (ex Ignyta) Ros1 & NTRK Approved for Ros1+ & NTRK+
Vitrakvi Larotrectinib/ Loxo-101 Bayer/Lilly (ex Loxo) NTRK Approved for NTRK+ (tumour agnostic)
Repotrectinib TPX-0005 BMS (ex Turning Point) Alk, Ros1 & NTRK Trident-1 (filing due 2022)
SIM1803-1A   Jiangsu Simcere Alk, Ros1 & NTRK NCT04671849
Taletrectinib AB-106/ DS-6051b Anheart/Daiichi Sankyo Alk, Ros1 & NTRK NCT04395677
Sitravatinib MGCD516 Mirati NTRK & various others Sapphire
Fochon Pharmaceuticals
Ros1 NCT04237805
Selitrectinib Loxo-195 Bayer/Lilly (ex Loxo) NTRK NCT03215511
Fochon Pharmaceuticals
NTRK NCT04687423
PBI-200   Pyramid Biosciences NTRK NCT04901806
Ensartinib   Xcovery Alk exalt3
TPX-0131   BMS (ex Turning Point) Alk Forge-1
Source: company filings.

And, however unproven the Ros1 opportunity is, sellside enthusiasm has resulted in repotrectinib featuring among biotech’s biggest unpartnered assets. Its 2028 consensus forecast sales of $895m, according to Evaluate Pharma, will of course also include the tumour-agnostic indication of NTRK-mutated cancers.


Meanwhile, Sanofi relinquishing control of Libtayo yesterday looks like an acceptance that the French group missed the boat in PD-(L)1 inhibition – notwithstanding Mr Hudson’s earlier bluster.

For $900m up front, plus a $100m milestone and an 11% royalty – terms Wells Fargo analysts reckon amount to a $2.7bn deal value – rights now pass from Sanofi to Regeneron. The two companies had collaborated on Libtayo’s development since 2015, and on the discovery of other antibodies for many years before that.

But the discovery deal expired in 2017 without being extended, and Sanofi sold off its $13bn equity stake in Regeneron two years ago. Yesterday’s deal seems a logical extension of those moves; Sanofi is known to be keen on new business development, and perhaps Regeneron offered it a sum it could not turn down.

Indeed, however much hype Sanofi had whipped up around Libtayo, Regeneron stock fell 4% yesterday. Investors see Regeneron as overpaying, and some on the sellside agree: Wells Fargo analysts wrote in a note to clients that they did not like the deal, saying Libtayo was still a “show-me story”, and that Regeneron would now be less attractive as a buyout target.

Such considerations are important given that Regeneron is one of the few biotechs to have weathered the market downturn well.

Libtayo global forecast sales by indication ($m)
  2021 2022e 2023e 2024e 2025e 2026e 2027e 2028e
NSCLC 49 207 421 643 873 1,099 1,305 1,460
Squamous cell carcinoma 384 427 484 531 566 608 650 694
Basal cell carcinoma 26 71 95 116 135 153 169 186
Total 459 705 999 1,290 1,575 1,861 2,124 2,340
Source: Evaluate Pharma sellside consensus.

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