1/ #MondayNightIBD #Back2Basics   TL1A , a 🆕🎯for inflammation & ?fibrosis 3️⃣anti-TL1A mAbs w/ Ph 2 trials data +active Ph 3 for #UC & #Crohns ⚙️MOA, efficacy, safety 🆓CME 👉🏼mnibd.short.gy/TL1AsTW Support by an educational grant @Sanofi   📍Where are you in your career?

2/ #MondayNightIBD 🚧~40% mod-sev #IBD have no or LoR to current Rx 🎯TL1A: TNF superfamily member, binds DR3 on T cells, NK cells & ILCs 🥊Drives inflammation (Th1/Th17/Th2) AND fibrosis (fibroblast activation) 🥊anti-TL1A block TL1A–DR3 →⬇️innate + adaptive immunity

3/#MondayNightIBD 🎬Starting w #Duvakitug 🔥Hot off the press   🩺RELIEVE UCCD: Ph2b basket trial: Parallel UC+CD cohorts (~120 pts each) 💉1 Loading dose DUVA SC→DUVA SC 450mg Q2W vs 900mg Q2W vs PBO  🎯Primary end points @ Wk14  UC: Clin remission CD: Endo response

4/#MondayNightIBD RELIEVE-UCCD📊Wk14 outcomes in UC Bayesian trial→posterior probability(PP) ✅Clin remission(mMS) 48%(900mg)/ 36%(450mg) DUVA vs 20% PBO Δ26% PP >0.99 | Δ15% PP 0.95 ✅Endo Improvemt(MES 0/1) 50%(900mg)/ 45%(450mg) DUVA vs 23% PBO Δ26% PP >0.99 | Δ21% PP 0.99

5/#MondayNightIBD   RELIEVE UCCD 📊Wk 14 outcomes in #Crohns   🔦Endo Response (≥50% ↓ SES-CD) 48% (900mg)/ 26% (450mg) DUVA vs 13% PBO Δ33% PP >0.99 | Δ13% PP 0.94   🩺Clinical Remission (PRO2) 37%/37% DUVA vs 26% PBO Δ10% PP 0.87 (both doses)

6/#MondayNightIBD RELIEVE-UCCD LTE 🗞️ release (to be presented at upcoming meeting) 🔀Wk14 responders re-randomized to DUVA 900mg or 450mg SC Q4W to wk44   🎯Wk 44- UC clin remission (mMS)  900 mg: 58% 450 mg: 47%    🎯Wk 44- CD endo response (SES-CD) 900 mg: 55% 450 mg: 41%

7/ DUVA safety (RELIEVE UCCD Wk14)   🚫No⬆️ TEAE signal DUVA vs PBO 🚫No dose-dependent signal 🚫No deaths, CA, MACE, VTE 🧬ADAs low; no neutralizing antibodies ⚠️1 anaphylactic rxn (450mg CD); resolved 📌10 SAEs in 450mg CD arm in 1pt w/ severe COVID, judged unrelated to DUVA

8/ #MondayNightIBD 🎬Next: Tulisokibart Phase2️⃣trials 🏹ARTEMIS-UC (UC) 🎻APOLLO-CD (CD) 💉TULI 1,000mg IV wk0, then 500mg IV wk 2, 6, 10   OLE: Wk12 responders: 🔀randomized 250 or 100mg IV Tuli Q4W

9/#MondayNightIBD 🏹ARTEMIS-UC  📊Week 12 outcomes ✅Clin remission: 26% TULI vs 1.5% PBO (Δ +25%, p<0.001) ✅Endoscopic improvement: 37% TULI vs 6% PBO (Δ +31%, p<0.001)

10/#MondayNightIBD ARTEMIS-UC OLE OLE study: TULI Wk 12 responders 🔀 250 vs 100mg IV TULI Q4W   Outcomes at Wk50: 🩺Clinical remission: 48%/32% 🔦Endo response: 48%/36% 🆑Disease clearance (symptomatic+mucosal remission): 44%/32%

11/ #MondayNightIBD 🎻APOLLO-CD 📊TULI Week 12 outcomes   ✅ Clin remission (CDAI <150): 49% (27/55) ✅Endo response (≥50% ↓ SES-CD): 26% (13/50)   ⏳OLE: Wk 12 responders 🔀IV 250mg or 100 mg Q4W At week 50 💎Clinical remission: 56%/42% 💎Endo response 28%/16%

12/ TULI safety (ARTEMIS-UC + APOLLO-CD) 🚫No ⬆️AEs signals Tuli vs PBO 🚫No deaths, infusion rxns, serious infections 🧬ADAs low, no impact on efficacy ⚠️1 Bowen's disease — related per investigator, unrelated per sponsor

13/ 🎬Finally, Afimkibart   🌻TUSCANY-2 (Ph2b, UC) RCT 💉Induction AFIM SC 50/150/450mg Q4W through Wk 14 vs PBO →Treat through to wk56 w one of 3 AFIM doses Q4W 🎯Primary endpt: clinical remission tMS 2 or less     *Afim Ph2 data is UC-only; no CD trial data reported yet

14/ #MondayNightIBD TUSCANY-2: Wk14 induction AFIM in UC   🩺Clin Rem by mMS: 450 mg: 32% (Δ +20% vs PBO) 150 mg: 35% (Δ +23%)  50 mg: 30% (Δ +18%) PBO: 12%   ⚠️Endpoint did not reach statistical significance per tMS, but meaningful improvemt by mMS & ⬇️ in FCP across all doses

15/#MondayNightIBD TUSCANY-2  Wk 14 endo outcomes AFIM in UC:   🔦Endo improvement: 450mg 41% 150 mg 38% 50mg 40% vs PBO 19% Δ ~20 pp across all doses

16/ #MondayNightIBD TUSCANY-2 in UC wk56 data:   Same-dose clinical remission (mMS) from wk 14 to wk56   450mg: 29% →36% 150mg: 38% → 39% 50mg: 30% → 31% 🩺Remission was sustained across all doses w modest gain at highest dose

17/ #MondayNightIBD AFIM safety 🚫no ⬆️TEAEs signal Afim vs PBO at all doses 🚫No deaths
🚫No new signals 📌Common AEs (≥5%): nausea, UTI, UC flare, anemia, fatigue, headache, pyrexia

18/ #MondayNightIBD 🔥Anti-TL1A-Exciting 🆕 MOA 🧘🏽‍♀️RELIEVE-UCCD/DUVA 🏹ARTEMIS-UC & 🎻APPOLO-CD/TULI 🌻TUSCANY(UC)/AFIM ✅Meaningful induction efficacy ✅Efficacy maintained at 1yr ✅👌🏽 Safety, no class 🚩 ✅Low immunogenicity 💬What are you mostly excited about for this MOA?

19/ #MondayNightIBD #PostB2B #IBDPoll 1️⃣ 🆓#CME👉🏼 mnibd.short.gy/TL1AsTWpost   🧩TNF-like cytokine 1A (TL1A) bind to which receptor to drive inflammation (& fibrosis) in the gut? (😉 check tweet 2 of this 🧵)