Malcolm Tan
@ibdgastrodocsg.bsky.social
Gastroenterologist | IBD Service Director | Singapore General Hospital.
7/🧵
Clinical response rates were consistent.... even for those with 4+ prior AT: 55% clinical response
In JAK-IR: 55% clinical response
Clinical response rates were consistent.... even for those with 4+ prior AT: 55% clinical response
In JAK-IR: 55% clinical response
October 20, 2025 at 1:48 AM
7/🧵
Clinical response rates were consistent.... even for those with 4+ prior AT: 55% clinical response
In JAK-IR: 55% clinical response
Clinical response rates were consistent.... even for those with 4+ prior AT: 55% clinical response
In JAK-IR: 55% clinical response
6/🧵
Obefazimod works in patients with prior AT-IR, perhaps not as well as in AT-naive patients.
Obefazimod works in patients with prior AT-IR, perhaps not as well as in AT-naive patients.
October 20, 2025 at 1:48 AM
6/🧵
Obefazimod works in patients with prior AT-IR, perhaps not as well as in AT-naive patients.
Obefazimod works in patients with prior AT-IR, perhaps not as well as in AT-naive patients.
5/🧵
Obefazimod was generally well-tolerated. Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) were comparable across all three groups (Placebo, 25mg, 50mg). Headaches did not result in treatment cessation.
Obefazimod was generally well-tolerated. Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) were comparable across all three groups (Placebo, 25mg, 50mg). Headaches did not result in treatment cessation.
October 20, 2025 at 1:48 AM
5/🧵
Obefazimod was generally well-tolerated. Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) were comparable across all three groups (Placebo, 25mg, 50mg). Headaches did not result in treatment cessation.
Obefazimod was generally well-tolerated. Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) were comparable across all three groups (Placebo, 25mg, 50mg). Headaches did not result in treatment cessation.
4/🧵
Both Obefazimod doses achieved clinically meaningful improvements across ALL efficacy endpoints in the pooled dataset. The (higher) 50mg dose showed superior outcomes.
Both Obefazimod doses achieved clinically meaningful improvements across ALL efficacy endpoints in the pooled dataset. The (higher) 50mg dose showed superior outcomes.
October 20, 2025 at 1:48 AM
4/🧵
Both Obefazimod doses achieved clinically meaningful improvements across ALL efficacy endpoints in the pooled dataset. The (higher) 50mg dose showed superior outcomes.
Both Obefazimod doses achieved clinically meaningful improvements across ALL efficacy endpoints in the pooled dataset. The (higher) 50mg dose showed superior outcomes.
3/ 🧵
Notably, the study included a highly refractory population, with ~21% having prior AT-IR (inadequate response) failing a JAK inhibitor.
Notably, the study included a highly refractory population, with ~21% having prior AT-IR (inadequate response) failing a JAK inhibitor.
October 20, 2025 at 1:48 AM
3/ 🧵
Notably, the study included a highly refractory population, with ~21% having prior AT-IR (inadequate response) failing a JAK inhibitor.
Notably, the study included a highly refractory population, with ~21% having prior AT-IR (inadequate response) failing a JAK inhibitor.
2/🧵
The ABTECT Phase 3 program includes 2 induction trials & 1 maintenance trial. Our focus today is on the strong safety and efficacy results from the ABTECT 1 & 2 induction phases.
The ABTECT Phase 3 program includes 2 induction trials & 1 maintenance trial. Our focus today is on the strong safety and efficacy results from the ABTECT 1 & 2 induction phases.
October 20, 2025 at 1:48 AM
2/🧵
The ABTECT Phase 3 program includes 2 induction trials & 1 maintenance trial. Our focus today is on the strong safety and efficacy results from the ABTECT 1 & 2 induction phases.
The ABTECT Phase 3 program includes 2 induction trials & 1 maintenance trial. Our focus today is on the strong safety and efficacy results from the ABTECT 1 & 2 induction phases.
9/ Bottom line
IUS finds subclinical inflammation, drives earlier treatment, reduces invasive tests & emissions.
📄 Full study: doi.org/10.1080/0036...
@yiyuantan.bsky.social @justinleongwh.bsky.social @tandfresearch.bsky.social
IUS finds subclinical inflammation, drives earlier treatment, reduces invasive tests & emissions.
📄 Full study: doi.org/10.1080/0036...
@yiyuantan.bsky.social @justinleongwh.bsky.social @tandfresearch.bsky.social
https://doi.org/10.1080/00365521.2025.2533338
t.co
August 10, 2025 at 6:31 AM
9/ Bottom line
IUS finds subclinical inflammation, drives earlier treatment, reduces invasive tests & emissions.
📄 Full study: doi.org/10.1080/0036...
@yiyuantan.bsky.social @justinleongwh.bsky.social @tandfresearch.bsky.social
IUS finds subclinical inflammation, drives earlier treatment, reduces invasive tests & emissions.
📄 Full study: doi.org/10.1080/0036...
@yiyuantan.bsky.social @justinleongwh.bsky.social @tandfresearch.bsky.social
8/ Limitations
Operator dependent
Limited for proximal small bowel / extramural complications
But as an alternative to endoscopy/MRE, it’s a game changer
Operator dependent
Limited for proximal small bowel / extramural complications
But as an alternative to endoscopy/MRE, it’s a game changer
August 10, 2025 at 6:31 AM
8/ Limitations
Operator dependent
Limited for proximal small bowel / extramural complications
But as an alternative to endoscopy/MRE, it’s a game changer
Operator dependent
Limited for proximal small bowel / extramural complications
But as an alternative to endoscopy/MRE, it’s a game changer
7/ Cost & planet wins 🌱
💰 USD $92,069 saved
🌍 2,752 kg CO₂e cut (≈ driving 14,000 km less)
IUS isn’t just good medicine – it’s good climate action
💰 USD $92,069 saved
🌍 2,752 kg CO₂e cut (≈ driving 14,000 km less)
IUS isn’t just good medicine – it’s good climate action
August 10, 2025 at 6:31 AM
7/ Cost & planet wins 🌱
💰 USD $92,069 saved
🌍 2,752 kg CO₂e cut (≈ driving 14,000 km less)
IUS isn’t just good medicine – it’s good climate action
💰 USD $92,069 saved
🌍 2,752 kg CO₂e cut (≈ driving 14,000 km less)
IUS isn’t just good medicine – it’s good climate action
6/ Impact on care
27% → treatment escalation
Discordant IUS findings → higher escalation (p=0.017)
60% avoided colonoscopy or MRE after IUS
That’s big for patients and endoscopy waitlists
27% → treatment escalation
Discordant IUS findings → higher escalation (p=0.017)
60% avoided colonoscopy or MRE after IUS
That’s big for patients and endoscopy waitlists
August 10, 2025 at 6:31 AM
6/ Impact on care
27% → treatment escalation
Discordant IUS findings → higher escalation (p=0.017)
60% avoided colonoscopy or MRE after IUS
That’s big for patients and endoscopy waitlists
27% → treatment escalation
Discordant IUS findings → higher escalation (p=0.017)
60% avoided colonoscopy or MRE after IUS
That’s big for patients and endoscopy waitlists
5/ Our findings 😲
63% in clinical remission…
But only 32% in transmural remission on IUS
➡️ Almost HALF of “well” patients still had active disease
63% in clinical remission…
But only 32% in transmural remission on IUS
➡️ Almost HALF of “well” patients still had active disease
August 10, 2025 at 6:31 AM
5/ Our findings 😲
63% in clinical remission…
But only 32% in transmural remission on IUS
➡️ Almost HALF of “well” patients still had active disease
63% in clinical remission…
But only 32% in transmural remission on IUS
➡️ Almost HALF of “well” patients still had active disease
4/ Our prospective study
48 patients, 60 IUS assessments:
- CD: 57%
- UC: 43%
Compared clinical, biochemical & IUS findings
Tracked changes in management + avoided procedures (MRE/Colonoscopy)
48 patients, 60 IUS assessments:
- CD: 57%
- UC: 43%
Compared clinical, biochemical & IUS findings
Tracked changes in management + avoided procedures (MRE/Colonoscopy)
August 10, 2025 at 6:31 AM
4/ Our prospective study
48 patients, 60 IUS assessments:
- CD: 57%
- UC: 43%
Compared clinical, biochemical & IUS findings
Tracked changes in management + avoided procedures (MRE/Colonoscopy)
48 patients, 60 IUS assessments:
- CD: 57%
- UC: 43%
Compared clinical, biochemical & IUS findings
Tracked changes in management + avoided procedures (MRE/Colonoscopy)
3/ Why this matters:
Colonoscopy & MRE are gold standards but…
❌ Costly
❌ Long wait times
❌ Sedation/bowel prep
❌ CO₂e emissions up to 55 kg/procedure
Colonoscopy & MRE are gold standards but…
❌ Costly
❌ Long wait times
❌ Sedation/bowel prep
❌ CO₂e emissions up to 55 kg/procedure
August 10, 2025 at 6:31 AM
3/ Why this matters:
Colonoscopy & MRE are gold standards but…
❌ Costly
❌ Long wait times
❌ Sedation/bowel prep
❌ CO₂e emissions up to 55 kg/procedure
Colonoscopy & MRE are gold standards but…
❌ Costly
❌ Long wait times
❌ Sedation/bowel prep
❌ CO₂e emissions up to 55 kg/procedure
2/ What is IUS?
No prep 🛑
No radiation ☢️
Point-of-care, takes minutes ⏱️
Sees transmural inflammation, not just mucosa
Minimal carbon footprint ♻️
No prep 🛑
No radiation ☢️
Point-of-care, takes minutes ⏱️
Sees transmural inflammation, not just mucosa
Minimal carbon footprint ♻️
August 10, 2025 at 6:31 AM
2/ What is IUS?
No prep 🛑
No radiation ☢️
Point-of-care, takes minutes ⏱️
Sees transmural inflammation, not just mucosa
Minimal carbon footprint ♻️
No prep 🛑
No radiation ☢️
Point-of-care, takes minutes ⏱️
Sees transmural inflammation, not just mucosa
Minimal carbon footprint ♻️
For gastroenterologists and IBD clinicians, TL1A blockade may represent the next chapter in mechanism-based IBD treatment.
@lancetgastrohep.bsky.social @robbrierley.bsky.social
#GISky #IBDSky #MedSky
@lancetgastrohep.bsky.social @robbrierley.bsky.social
#GISky #IBDSky #MedSky
June 27, 2025 at 7:56 AM
For gastroenterologists and IBD clinicians, TL1A blockade may represent the next chapter in mechanism-based IBD treatment.
@lancetgastrohep.bsky.social @robbrierley.bsky.social
#GISky #IBDSky #MedSky
@lancetgastrohep.bsky.social @robbrierley.bsky.social
#GISky #IBDSky #MedSky
Takeaway:
Tulisokibart appears safe and potentially efficacious in CD patients with high prior biologic exposure.
Early signals of both anti-inflammatory and anti-fibrotic activity suggest a dual mechanism worth watching.
A phase 3 trial is underway. 🧪
Tulisokibart appears safe and potentially efficacious in CD patients with high prior biologic exposure.
Early signals of both anti-inflammatory and anti-fibrotic activity suggest a dual mechanism worth watching.
A phase 3 trial is underway. 🧪
June 27, 2025 at 7:56 AM
Takeaway:
Tulisokibart appears safe and potentially efficacious in CD patients with high prior biologic exposure.
Early signals of both anti-inflammatory and anti-fibrotic activity suggest a dual mechanism worth watching.
A phase 3 trial is underway. 🧪
Tulisokibart appears safe and potentially efficacious in CD patients with high prior biologic exposure.
Early signals of both anti-inflammatory and anti-fibrotic activity suggest a dual mechanism worth watching.
A phase 3 trial is underway. 🧪
Biomarker & histology insights:
- ↓ hsCRP & fecal calprotectin by Week 6
- ↓ Th1, Th17 cytokines (IL-17A, IL-22, IL-9)
- ↓ fibrotic gene expression (e.g., COL1A1, MMP3)
- Histologic remission (RHI <3) in 18%
- ↓ hsCRP & fecal calprotectin by Week 6
- ↓ Th1, Th17 cytokines (IL-17A, IL-22, IL-9)
- ↓ fibrotic gene expression (e.g., COL1A1, MMP3)
- Histologic remission (RHI <3) in 18%
June 27, 2025 at 7:56 AM
Biomarker & histology insights:
- ↓ hsCRP & fecal calprotectin by Week 6
- ↓ Th1, Th17 cytokines (IL-17A, IL-22, IL-9)
- ↓ fibrotic gene expression (e.g., COL1A1, MMP3)
- Histologic remission (RHI <3) in 18%
- ↓ hsCRP & fecal calprotectin by Week 6
- ↓ Th1, Th17 cytokines (IL-17A, IL-22, IL-9)
- ↓ fibrotic gene expression (e.g., COL1A1, MMP3)
- Histologic remission (RHI <3) in 18%
Safety:
- AEs: 78% (mostly mild-moderate)
- SAEs: 15% (none drug-related)
- No deaths, no infusion reactions
- Most common AE: infection (45%), incl. COVID-19 (11%)
- AEs: 78% (mostly mild-moderate)
- SAEs: 15% (none drug-related)
- No deaths, no infusion reactions
- Most common AE: infection (45%), incl. COVID-19 (11%)
June 27, 2025 at 7:56 AM
Safety:
- AEs: 78% (mostly mild-moderate)
- SAEs: 15% (none drug-related)
- No deaths, no infusion reactions
- Most common AE: infection (45%), incl. COVID-19 (11%)
- AEs: 78% (mostly mild-moderate)
- SAEs: 15% (none drug-related)
- No deaths, no infusion reactions
- Most common AE: infection (45%), incl. COVID-19 (11%)
Primary efficacy results (Week 12):
- Endoscopic response (≥50% ↓ in SES-CD): 26.0%
vs historical placebo 12% (p=0.0023)
- Clinical remission (CDAI <150): 49.1%
vs historical placebo 16% (p<0.0001)
- Endoscopic response (≥50% ↓ in SES-CD): 26.0%
vs historical placebo 12% (p=0.0023)
- Clinical remission (CDAI <150): 49.1%
vs historical placebo 16% (p<0.0001)
June 27, 2025 at 7:56 AM
Primary efficacy results (Week 12):
- Endoscopic response (≥50% ↓ in SES-CD): 26.0%
vs historical placebo 12% (p=0.0023)
- Clinical remission (CDAI <150): 49.1%
vs historical placebo 16% (p<0.0001)
- Endoscopic response (≥50% ↓ in SES-CD): 26.0%
vs historical placebo 12% (p=0.0023)
- Clinical remission (CDAI <150): 49.1%
vs historical placebo 16% (p<0.0001)
Trial design (N=55):
- Multicentre, open-label
- Moderate-to-severe CD
- IV tulisokibart: 1000 mg (Day 1), 500 mg (Weeks 2, 6, 10)
- Endoscopic response at Week 12 = primary endpoint
71% had prior biologic exposure; 35% had ≥3 agents
- Multicentre, open-label
- Moderate-to-severe CD
- IV tulisokibart: 1000 mg (Day 1), 500 mg (Weeks 2, 6, 10)
- Endoscopic response at Week 12 = primary endpoint
71% had prior biologic exposure; 35% had ≥3 agents
June 27, 2025 at 7:56 AM
Trial design (N=55):
- Multicentre, open-label
- Moderate-to-severe CD
- IV tulisokibart: 1000 mg (Day 1), 500 mg (Weeks 2, 6, 10)
- Endoscopic response at Week 12 = primary endpoint
71% had prior biologic exposure; 35% had ≥3 agents
- Multicentre, open-label
- Moderate-to-severe CD
- IV tulisokibart: 1000 mg (Day 1), 500 mg (Weeks 2, 6, 10)
- Endoscopic response at Week 12 = primary endpoint
71% had prior biologic exposure; 35% had ≥3 agents
Why TL1A?
TL1A (TNFSF15) is a key driver of Th1/Th17-mediated inflammation and intestinal fibrosis—two critical components of CD pathogenesis.
Tulisokibart blocks TL1A from binding to its receptor DR3, dampening both inflammation and fibrotic signaling.
TL1A (TNFSF15) is a key driver of Th1/Th17-mediated inflammation and intestinal fibrosis—two critical components of CD pathogenesis.
Tulisokibart blocks TL1A from binding to its receptor DR3, dampening both inflammation and fibrotic signaling.
June 27, 2025 at 7:56 AM
Why TL1A?
TL1A (TNFSF15) is a key driver of Th1/Th17-mediated inflammation and intestinal fibrosis—two critical components of CD pathogenesis.
Tulisokibart blocks TL1A from binding to its receptor DR3, dampening both inflammation and fibrotic signaling.
TL1A (TNFSF15) is a key driver of Th1/Th17-mediated inflammation and intestinal fibrosis—two critical components of CD pathogenesis.
Tulisokibart blocks TL1A from binding to its receptor DR3, dampening both inflammation and fibrotic signaling.
