No giving up on degradation for Novartis

The growing field of protein degradation already featured Novartis as a minor player, and today the Swiss group dipped another toe in the water. An early research tie-up with a private UK biotech, Dunad Therapeutics, will see oral covalent and protein-degrading small molecules developed against up to four targets. The deal involves a $24m up-front fee plus an undisclosed equity stake that will see Novartis join Epidarex Capital and Biogeneration Ventures as a key investor of Dunad, which was founded last year. If the signing fee looks looks small compared with other recent deals it pales into insignificance against the $1.5bn Bayer handed across in August to buy the private protein degradation company Vividion. Back in 2017 Novartis teamed up with the University of California, Berkeley to deploy small molecules attached to a complex that tags a targeted protein for degradation. The most clinically advanced protein degraders are the Serds in breast cancer, an area in which Radius recently scored a pivotal success that could lead to a 2022 filing. Novartis’s own Serd, LSZ102, yielded an objective response rate of just 1% as monotherapy at Asco 2020, and its study was recently terminated.

Targeted protein degradation: selected small players*
Company  Valuation Notable deals/progress in protein degradation
Vividion Bought for up to $2bn by Bayer; had raised $271m in VC cash since 2017 Preclinical; 2019 Roche discovery deal ($135m up front); 2018 Celgene discovery deal ($110m up front)
Arvinas Market cap $4.7bn (Nasdaq listed) Licensed ph2 ARV-471 to Pfizer for $650m up front (proof-of-concept data Q4 2021); 2019 Bayer deal (incl agriculture applications) for $110m up front
Kymera $3.2bn market cap (Nasdaq listed) Irak4 degrader KT-474 in ph1, being developed under broad deal with Sanofi ($150m up front)
C4 Therapeutics $2.2bn market cap (Nasdaq listed) IKZF1/3 degrader CFT7455 in ph1; 2016 discovery deal with Roche extended in 2019
Nurix $1.5bn market cap (Nasdaq listed) BTK degrader NX-2127 in ph1; 2020 Sanofi deal ($55m up front); 2019 Gilead deal ($45m up front)
Monte Rosa Therapeutics $1.1bn market cap (Nasdaq listed) Preclinical
Olema $1.1bn market cap (Nasdaq listed) OP-1250 in ph1/2, future combo with Ibrance
Radius $1bn market cap (Nasdaq listed) Full pivotal data on Menarini-partnered elacestrant due at SABCS, Dec 2021
Roivant Floated via Spac, market cap $480m Bought Silicon Therapeutics to boost platform for $450m in stock
Seed Therapeutics Beyondspring subsidiary 2020 discovery deal with Lilly ($10m up front)
Cullgen Raised $81m in VC cash since 2018 Plans IND later this year for TRK protein degrader CG001419
Plexium Raised $63m in VC cash since 2019 Preclinical
Lycia Therapeutics Launched in 2020 with $50m VC cash; $70m series B Sep 2021 Preclinical; 2021 Lilly discovery deal ($35m up front); 2019 Roche discovery deal ($135m up front); 2018 Celgene discovery deal ($110m up front)
Mission Therapeutics Raised $184m in VC cash (incl from Pfizer Venture) since 2011 Research deal with Abbvie over deubiquitylating enzymes to treat Alzheimer’s and Parkinson’s
Frontier Medicines Raised $155m in VC cash since 2019 Preclinical; 2020 discovery deal with Abbvie ($55m up front)
Cedilla Therapeutics $56m series A Apr 2018; $83m series B Oct 2021 Preclinical; ongoing degrader work unclear
Dunad Therapeutics $6.9m series A Mar 2021 Preclinical; 2021 Novartis discovery deal ($24m up front + equity)
Note: *not exhaustive, and excludes big pharma players; this list was updated to remove Palleon Pharmaceuticals, which is not involved in protein degradation. Source: Evaluate Pharma & company statements.

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