Abbvie’s ROR ends with a whimper

Only a week after Immunic disappointed with its RORγ inverse agonist IMU-935, Abbvie has thrown in the towel on its similarly acting contender, ABBV-157. On Friday’s earnings call the big pharma slipped out the news of the discontinuation, citing new findings in a preclinical toxicology study of the project, which had been in phase 2 for psoriasis. This is another nail in the coffin for this class, which has seen the termination of various projects – often on toxicity concerns – including a previous effort from Abbvie and its partner Inventiva. Hitting RORγ has been pursued because of its ability to lower levels of IL-17, a cytokine implicated in autoimmune diseases and currently targeted by antibodies like Novartis’s Cosentyx. However, systemic RORγ inhibition can potentially cause progressive thymic dysregulation leading to thymic lymphoma, SVB analysts noted. There are not many other RORγ assets still in play, a look at the pipeline shows – although Immunic hopes to continue development of IMU-935 in psoriasis. Abbvie’s setback could be good news for the likes of Dice, which reported promising early data recently with its oral IL-17 inhibitor DC-806, and for others developing differently acting oral autoimmune therapies, such the Tyk2 inhibitors.

Selected small molecules with activity to lower IL-17
Project Company Pharmacology Status
DC-806 (S011806) Dice Therapeutics  IL-17 inhibitor Ph1 in psoriasis showed 44% mean PASI reduction in pts on high dose
LEO 153339 Leo Pharma IL-17 inhibitor Ph1 in healthy volunteers completes Nov 2022
AUR-101 Aurigene (Dr Reddy's subsidiary) RORγ inverse agonist Ph2 Indus-3 in psoriasis completes Nov 2022
XT-0528 (prev ARN-6039/BOS-172767) Xenter/Arrien RORyt inverse agonist Completed ph1, licensed to Xenter Jun 2021; ph1 to start in cancer
ABBV-157 (cedirogant) Abbvie/Inventiva RORyt inverse agonist Ph2 in psoriasis discontinued after preclinical tox findings
IMU-935 Immunic Therapeutics RORγ inverse agonist Failed to beat placebo in ph1 psoriasis study
BI 730357 Boehringer Ingelheim RORγ antagonist Discontinued in ph2 (psoriatic arthritis)
VTP-43742 Allergan (via Vitae) RORγt inverse agonist Terminated due to tox signals in ph2
BMS-986251 Bristol Myers Squibb RORγt inverse agonist Ph1/2 in psoriasis terminated ("adverse changes in risk/benefit")
GSK2981278  GSK Topical RORγ inverse agonist Abandoned after ph1/2 in psoriasis
LY3509754 Lilly IL-17A inhibitor Ph1 in psoriasis terminated after undisclosed liver findings
AZD0284 Astrazeneca RORγ inverse agonist Ph1 in psoriasis terminated after preclinical findings
SAR441169 Lead Pharma/ Sanofi RORγ inverse agonist Ph1 in psoriasis terminated
ABBV-553 Abbvie/Inventiva RORγ inverse agonist Ph1 in psoriasis terminated on undisclosed safety reason
TAK-828F Takeda RORγt inverse agonist Ph1 in Crohn's discontinued after preclinical toxicology & clinical teratogenicity findings
Source: Evaluate Pharma &

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