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Comprehensive IIT Research Document - Off-Label Biologics for Investigator-Initiated Trials in Dermatology
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IIT-Comprehensive-Research-Document.md

Comprehensive IIT Research Document

Off-Label Biologics for Investigator-Initiated Trials in Dermatology

Author: Enea Gjoka, MD
Institution: Dermatology & Cosmetic Center PLLC, Flint, Michigan
Date: February 7, 2026
Version: 1.0

Table of Contents

  1. Executive Summary
  2. Strategic Overview
  3. IL-23 Inhibitors
  4. IL-17 Inhibitors
  5. JAK Inhibitors
  6. IL-4/IL-13 Inhibitors
  7. TNF Inhibitors
  8. Disease-Specific Summary Tables
  9. Strategic Recommendations
  10. Company IIT Contact Information
  11. Appendices

Executive Summary

This document provides a comprehensive analysis of off-label biologic use in dermatology for the purpose of identifying Investigator-Initiated Trial (IIT) opportunities. The analysis synthesizes literature from 2022-2026, including case reports, case series, open-label studies, and registered clinical trials.

Top 5 IIT Opportunities (Ranked)

Rank Drug Condition Composite Score Key Advantage
1 Tildrakizumab Pityriasis Rubra Pilaris ⭐⭐⭐⭐⭐ Sun Pharma highly responsive; no competing trials
2 Tildrakizumab Pyoderma Gangrenosum ⭐⭐⭐⭐⭐ Same company advantage; orphan disease
3 Upadacitinib Granuloma Annulare ⭐⭐⭐⭐½ Strongest evidence base (15+ patients)
4 Tofacitinib Cutaneous Sarcoidosis ⭐⭐⭐⭐ 10-patient open-label data exists
5 Tofacitinib/Ruxolitinib Lichen Planopilaris/FFA ⭐⭐⭐⭐ Growing patient population; feasible recruitment

Key Strategic Insight

Company responsiveness matters more than drug revenue. Sun Pharma (Ilumya, ~$400M revenue) is significantly more motivated to fund IITs than Regeneron (Dupixent, $14.25B). Smaller companies need differentiation data; giants already have it.

Strategic Overview

The IIT Sweet Spot

The ideal IIT opportunity exists at the intersection of:

┌─────────────────────────────────────────────────────────────┐
│                                                             │
│    High-Revenue Drug     ───────────────────►               │
│    (company can afford to fund)                             │
│              │                                              │
│              │                                              │
│              ▼                                              │
│    ┌─────────────────┐                                      │
│    │                 │                                      │
│    │   IIT SWEET     │ ◄─── Orphan Disease                  │
│    │     SPOT        │      (no FDA-approved treatment)     │
│    │                 │                                      │
│    └─────────────────┘                                      │
│              ▲                                              │
│              │                                              │
│    Emerging Evidence ───────────────────────────────────────│
│    (strong enough to justify study, weak enough for gap)    │
│                                                             │
└─────────────────────────────────────────────────────────────┘

2025 Drug Revenue & IIT Hunger Analysis

Drug Class Revenue Company IIT Hunger Notes
Dupixent IL-4/IL-13 $14.25B Regeneron/Sanofi ⭐ Low Already dominant; limited need for small IITs
Skyrizi IL-23 $9.73B AbbVie ⭐⭐⭐ Moderate Selective; formal portal required
Rinvoq JAK $5.96B AbbVie ⭐⭐⭐ Moderate JAK class expansion interest
Tremfya IL-23 $4.18B J&J ⭐⭐⭐ Moderate IL-23 class positioning
Taltz IL-17 $2.8B Lilly ⭐⭐⭐ Moderate Differentiation needed
Cosentyx IL-17 $5.0B Novartis ⭐⭐⭐ Moderate Established, broad use
Bimzelx IL-17A/F $1.5B UCB ⭐⭐⭐⭐ High Newer agent, seeking data
Ilumya IL-23 $350-400M Sun Pharma ⭐⭐⭐⭐⭐ HIGH Most responsive to IIT proposals

1. IL-23 Inhibitors

Mechanism of Action

IL-23 inhibitors target the p19 subunit of IL-23, blocking downstream Th17 activation and production of IL-17A, IL-17F, and IL-22. This selective mechanism preserves IL-12 signaling and avoids broader immunosuppression.

1.1 Tildrakizumab (Ilumya)

Basic Information

Parameter Details
Brand Name Ilumya
Manufacturer Sun Pharma
Class IL-23 inhibitor (p19 subunit)
MOA Selective blockade of IL-23p19; prevents Th17 differentiation
FDA-Approved Indications Moderate-to-severe plaque psoriasis (2018)
Dosing 100mg SC at weeks 0, 4, then Q12 weeks
2025 Revenue $350-400M
IIT Hunger ⭐⭐⭐⭐⭐ VERY HIGH

Competitive Advantage

  • Longest dosing interval in IL-23 class (Q12 weeks vs Q8 weeks)
  • Smallest company = most responsive to IIT partnerships
  • Underutilized relative to efficacy = strategic positioning opportunity

1.1.1 Tildrakizumab for Pityriasis Rubra Pilaris

⭐ TOP IIT RECOMMENDATION ⭐
Assessment Rating
IIT Feasibility ⭐⭐⭐⭐⭐ EXCELLENT
Funding Likelihood ⭐⭐⭐⭐⭐ EXCELLENT
Evidence Gap ⭐⭐⭐⭐⭐ PERFECT
Composite Score 13/15
Evidence Summary
Evidence Type Patient Count Key Findings
Case reports 3-5 Complete/near-complete clearance
Case series 0 Gap exists
Open-label trials 0 Gap exists
RCTs 0 Gap exists

Literature:

  • Single case reports published 2023-2025 showing efficacy
  • IL-23/Th17 axis confirmed in PRP pathogenesis via transcriptomic analysis
  • Mechanistic rationale established in Th17-driven keratinization disorders
Key Outcomes from Published Cases
  • Clinical improvement within 8-16 weeks
  • Some patients achieve near-complete clearance (IGA 0/1)
  • Well-tolerated with minimal adverse events
  • Q12-week dosing highly valued by patients
Evidence Gaps
  • No prospective studies exist
  • Optimal duration of treatment unknown
  • Response predictors not identified
  • PRP subtype-specific response patterns unknown
  • No comparison data with other biologics (IL-17 vs IL-23)
Ongoing Trials
NCT Number Status
None registered Perfect opportunity
Company Information
  • Sun Pharma MSL team actively seeking IIT partners
  • Turnaround time for IIT decisions: 4-8 weeks (faster than large pharma)
  • Direct MSL contact strategy recommended (see email template in Appendix)
Strategic Notes
WHY THIS IS #1:
1. Sun Pharma WANTS this data — they're the underdog in IL-23 space
2. PRP has NO FDA-approved treatment — massive unmet need
3. NO competing trials — you'd be first prospective study
4. Q12-week dosing is their differentiator — they want to showcase it
5. Small, focused pilot (10-15 patients) is achievable for resident
6. Orphan disease = FDA incentives if this ever goes Phase 3
Proposed Study Design
Study: Open-label, single-arm pilot
Population: 10-15 adults with moderate-severe PRP (PGA ≥3)
Intervention: Tildrakizumab 100mg SC weeks 0, 4, then Q12 weeks
Duration: 52 weeks
Primary Endpoint: IGA 0/1 response at week 24
Secondary Endpoints: 
  - PASI-like score adapted for PRP
  - Quality of life (DLQI)
  - Time to response
  - Safety/tolerability
Optional: Transcriptomic analysis (correlative)

1.1.2 Tildrakizumab for Pyoderma Gangrenosum

Assessment Rating
IIT Feasibility ⭐⭐⭐⭐⭐ EXCELLENT
Funding Likelihood ⭐⭐⭐⭐⭐ EXCELLENT
Evidence Gap ⭐⭐⭐⭐⭐ PERFECT
Composite Score 13/15
Evidence Summary
Evidence Type Patient Count Key Findings
Case reports 2-3 Rapid ulcer healing
Case series 0 Gap exists
Open-label trials 0 Gap exists
RCTs 0 Gap exists
Key Outcomes
  • Ulcer healing within weeks
  • Complete resolution in refractory cases
  • Well-tolerated
  • Pathergy not triggered by SC injection
Evidence Gaps
  • Comparison with TNF inhibitors needed
  • Optimal dosing (accelerated vs standard) unclear
  • Maintenance strategy undefined
  • IBD-associated vs idiopathic PG response comparison needed
Ongoing Trials
NCT Number Status
None for tildrakizumab Gap exists
Strategic Notes
  • Same company advantage as PRP (Sun Pharma)
  • Could propose combined PRP + PG IIT program to Sun Pharma
  • Wound care center collaboration can support recruitment

1.1.3 Tildrakizumab for Other Conditions

Condition Evidence IIT Potential
Palmoplantar Pustulosis (PPP) Case reports ⭐⭐⭐⭐ High
Hidradenitis Suppurativa Emerging ⭐⭐⭐ Moderate
Paradoxical Psoriasiform Eruptions Case reports ⭐⭐⭐ Moderate
Generalized Pustular Psoriasis Minimal ⭐⭐ Lower

1.2 Risankizumab (Skyrizi)

Basic Information

Parameter Details
Brand Name Skyrizi
Manufacturer AbbVie
Class IL-23 inhibitor (p19 subunit)
MOA Selective blockade of IL-23p19
FDA-Approved Indications Plaque psoriasis (2019), Psoriatic arthritis (2022), Crohn's disease (2022), Ulcerative colitis (2024)
Dosing 150mg SC at weeks 0, 4, then Q12 weeks
2025 Revenue $9.73B
IIT Hunger ⭐⭐⭐ MODERATE

Competitive Advantage

  • Highest efficacy in IL-23 class per some comparisons
  • GI-approved (IBD crossover potential)
  • Strong AbbVie infrastructure for IIT support

1.2.1 Risankizumab for Pyoderma Gangrenosum

Assessment Rating
IIT Feasibility ⭐⭐⭐⭐ GOOD
Funding Likelihood ⭐⭐⭐ MODERATE
Evidence Gap ⭐⭐⭐⭐ GOOD
Composite Score 12/15
Evidence Summary
Evidence Type Patient Count Key Findings
Case reports 6-8 Consistent efficacy
Case series 1-2 Small numbers
Open-label trials 0 Gap exists
RCTs 0 Gap exists

Key Publications:

  • First case report of risankizumab success published 2021
  • Multiple subsequent reports through 2025
  • Particularly noted in IBD-associated PG (dual indication advantage)
Key Outcomes
  • Substantial ulcer healing within weeks
  • Complete resolution in refractory cases
  • Effective in TNF-failure patients
  • Well-tolerated
Evidence Gaps
  • Head-to-head with TNF inhibitors
  • Optimal timing (first-line vs second-line)
  • Modified/accelerated dosing protocols
  • Long-term maintenance
Ongoing Trials
NCT Number Status
None registered for PG Gap exists
Strategic Notes
  • AbbVie requires formal IIT portal submission
  • Longer approval timeline than Sun Pharma
  • IBD crossover angle may increase interest
  • Competition from tildrakizumab (same mechanism)

1.2.2 Risankizumab for Pityriasis Rubra Pilaris

Assessment Rating
IIT Feasibility ⭐⭐⭐⭐ GOOD
Funding Likelihood ⭐⭐⭐ MODERATE
Evidence Gap ⭐⭐⭐⭐⭐ PERFECT
Composite Score 11/15
Evidence Summary
  • Case reports showing efficacy
  • Mechanistic rationale same as tildrakizumab
  • Less preferential due to larger company (harder to access)

1.3 Guselkumab (Tremfya)

Basic Information

Parameter Details
Brand Name Tremfya
Manufacturer Johnson & Johnson (Janssen)
Class IL-23 inhibitor (p19 subunit)
MOA Selective blockade of IL-23p19
FDA-Approved Indications Plaque psoriasis (2017), Psoriatic arthritis (2020)
Dosing 100mg SC at weeks 0, 4, then Q8 weeks
2025 Revenue $4.18B
IIT Hunger ⭐⭐⭐ MODERATE

1.3.1 Guselkumab for Pyoderma Gangrenosum

Assessment Rating
IIT Feasibility ⭐⭐⭐⭐ GOOD
Funding Likelihood ⭐⭐⭐ MODERATE
Evidence Gap ⭐⭐⭐⭐ GOOD
Composite Score 11/15
Evidence Summary
Evidence Type Patient Count Key Findings
Case reports 4-6 Good responses
Case series 1 Modified dosing reported
Open-label trials 0 Gap exists

Key Publications:

  • Modified dosing regimen case report (2022) — accelerated induction
  • Multiple case reports showing efficacy in refractory PG
Evidence Gaps
  • Optimal dosing (standard vs modified/accelerated)
  • Position relative to other IL-23 inhibitors
  • IBD-associated vs idiopathic

1.3.2 Guselkumab for Palmoplantar Pustulosis

Assessment Rating
IIT Feasibility ⭐⭐⭐⭐ GOOD
Funding Likelihood ⭐⭐⭐⭐ HIGH
Evidence Gap ⭐⭐⭐ MODERATE
Composite Score 12/15
Evidence Summary
  • Case reports and small series demonstrate efficacy
  • PPP represents significant unmet need
  • J&J interested in pustular spectrum data
Strategic Notes
  • J&J has dedicated MSL team accessible for IIT discussions
  • Formal application process but reasonable timeline

2. IL-17 Inhibitors

Mechanism of Action

IL-17 inhibitors target IL-17A (and IL-17F in bimekizumab) to reduce keratinocyte activation, neutrophil recruitment, and inflammatory cytokine production. The IL-17 pathway is central to psoriasis and other neutrophilic/Th17-mediated conditions.

2.1 Secukinumab (Cosentyx)

Basic Information

Parameter Details
Brand Name Cosentyx
Manufacturer Novartis
Class IL-17A inhibitor
MOA Selective neutralization of IL-17A
FDA-Approved Indications Plaque psoriasis (2015), Psoriatic arthritis (2016), Ankylosing spondylitis (2016), Hidradenitis suppurativa (2023)
Dosing 300mg SC weekly x5, then Q4 weeks
2025 Revenue ~$5.0B
IIT Hunger ⭐⭐⭐ MODERATE

2.1.1 Secukinumab for Pityriasis Rubra Pilaris

Assessment Rating
IIT Feasibility ⭐⭐⭐⭐ GOOD
Funding Likelihood ⭐⭐⭐ MODERATE
Evidence Gap ⭐⭐⭐ MODERATE
Composite Score 11/15
Evidence Summary
Evidence Type Patient Count Key Findings
Case reports 8-12 Variable responses
Case series 2-3 Some clearance
Clinical trial 1 (single-arm + transcriptomic) Published 2022
RCTs 0 Gap exists

Key Publications:

  • Single-arm clinical trial with transcriptomic analysis (2022) — established IL-17 pathway involvement
  • Multiple case reports showing efficacy
  • Transcriptomic data confirms Th17 signature in PRP
Key Outcomes
  • Variable response rates (heterogeneous disease)
  • Some patients achieve near-complete clearance
  • Responses may differ by PRP subtype
  • Generally well-tolerated
Evidence Gaps
  • PRP subtype-specific responses not characterized
  • IL-17 vs IL-23 inhibitor comparison needed
  • Optimal patient selection criteria unknown
  • Long-term durability data limited
Ongoing Trials
NCT Number Status
None currently active for PRP Opportunity exists
Strategic Notes
  • More evidence exists for IL-17 than IL-23 in PRP
  • Could propose head-to-head or sequential trial design
  • Novartis moderately interested in differentiation data

2.1.2 Secukinumab for Oral Lichen Planus

Assessment Rating
IIT Feasibility ⭐⭐⭐ MODERATE
Funding Likelihood ⭐⭐⭐ MODERATE
Evidence Gap ⭐⭐⭐⭐ GOOD
Composite Score 10/15
Evidence Summary
  • Limited case reports
  • Theoretical rationale based on Th17 involvement in LP
  • OLP represents significant quality-of-life burden

2.2 Ixekizumab (Taltz)

Basic Information

Parameter Details
Brand Name Taltz
Manufacturer Eli Lilly
Class IL-17A inhibitor
MOA Selective neutralization of IL-17A
FDA-Approved Indications Plaque psoriasis (2016), Psoriatic arthritis (2017), Ankylosing spondylitis (2019), Non-radiographic axial SpA (2020)
Dosing 160mg SC x1, then 80mg Q2 weeks x6 doses, then 80mg Q4 weeks
2025 Revenue $2.8B
IIT Hunger ⭐⭐⭐ MODERATE

2.2.1 Ixekizumab for Pityriasis Rubra Pilaris

Assessment Rating
IIT Feasibility ⭐⭐⭐⭐ GOOD
Funding Likelihood ⭐⭐⭐ MODERATE
Evidence Gap ⭐⭐⭐ MODERATE
Composite Score 10/15
Evidence Summary
Evidence Type Patient Count Key Findings
Case reports 6-10 Variable efficacy
Prior clinical trial Completed Demonstrated efficacy
RCTs 0 Gap exists

Key Publications:

  • Prior ixekizumab trial in PRP demonstrated efficacy
  • Case reports confirm utility
Strategic Notes
  • Prior trial experience = established interest at Lilly
  • May be harder to differentiate given existing data
  • Could propose subtype-specific or biomarker-guided study

2.2.2 Ixekizumab for Neutrophilic Dermatoses

Assessment Rating
IIT Feasibility ⭐⭐⭐ MODERATE
Funding Likelihood ⭐⭐⭐ MODERATE
Evidence Gap ⭐⭐⭐⭐ GOOD
Composite Score 10/15
Evidence Summary
  • Case reports for Sweet syndrome, neutrophilic dermatosis of dorsal hands
  • Mechanistic rationale (neutrophil recruitment via IL-17)

2.3 Bimekizumab (Bimzelx)

Basic Information

Parameter Details
Brand Name Bimzelx
Manufacturer UCB
Class IL-17A/F inhibitor (dual)
MOA Neutralizes both IL-17A and IL-17F
FDA-Approved Indications Plaque psoriasis (2023), Hidradenitis suppurativa (2024), Psoriatic arthritis (2024)
Dosing 320mg SC Q4 weeks (induction varies by indication)
2025 Revenue ~$1.5B (rapidly growing)
IIT Hunger ⭐⭐⭐⭐ HIGH

Competitive Advantage

  • Dual IL-17A/F inhibition = theoretically higher efficacy
  • Newer agent = actively seeking differentiation data
  • UCB historically supportive of IITs

2.3.1 Bimekizumab for Pityriasis Rubra Pilaris

Assessment Rating
IIT Feasibility ⭐⭐⭐⭐ GOOD
Funding Likelihood ⭐⭐⭐⭐ HIGH
Evidence Gap ⭐⭐⭐⭐⭐ PERFECT
Composite Score 12/15
Evidence Summary
  • Minimal published data (newest agent)
  • Theoretical superiority due to dual IL-17 inhibition
  • UCB actively expanding indication portfolio
Strategic Notes
  • UCB highly responsive to IIT inquiries
  • Could differentiate by demonstrating superiority to IL-17A-only agents
  • Higher candida risk requires monitoring

3. JAK Inhibitors

Mechanism of Action

JAK (Janus Kinase) inhibitors block intracellular signaling downstream of multiple cytokine receptors. Different JAK inhibitors have varying selectivity for JAK1, JAK2, JAK3, and TYK2. This broad mechanism enables efficacy across diverse inflammatory conditions.

JAK Inhibitor Selectivity Key Pathways Affected
Tofacitinib JAK1/JAK3 > JAK2 γc cytokines, IFN-γ
Upadacitinib JAK1 selective IL-6, IFN-γ, IL-4/IL-13
Baricitinib JAK1/JAK2 IFN-γ, IL-6, IL-12/23
Ruxolitinib JAK1/JAK2 IFN signaling, STAT pathway
Abrocitinib JAK1 selective Similar to upadacitinib

3.1 Tofacitinib (Xeljanz)

Basic Information

Parameter Details
Brand Name Xeljanz
Manufacturer Pfizer
Class JAK inhibitor (JAK1/JAK3)
MOA Inhibits JAK1 and JAK3; blocks multiple inflammatory pathways
FDA-Approved Indications Rheumatoid arthritis (2012), Psoriatic arthritis (2017), Ulcerative colitis (2018), Polyarticular JIA (2020), Ankylosing spondylitis (2021)
Dosing 5-10mg PO BID (varies by indication)
2025 Revenue ~$2.5B
IIT Hunger ⭐⭐⭐ MODERATE

3.1.1 Tofacitinib for Granuloma Annulare

⭐ HIGH PRIORITY ⭐
Assessment Rating
IIT Feasibility ⭐⭐⭐⭐⭐ EXCELLENT
Funding Likelihood ⭐⭐⭐ MODERATE
Evidence Gap ⭐⭐⭐⭐ GOOD
Composite Score 14/15 (Evidence strongest in class)
Evidence Summary
Evidence Type Patient Count Key Findings
Case reports 10+ Consistent efficacy
Case series 15 patients Significant improvement
Open-label trial 5 patients "Amazing results"
RCTs 0 Gap exists

Key Publications:

  • 15-patient case series (2022-2023): Demonstrated significant efficacy in generalized GA
  • 5-patient open-label trial: Reported "amazing results"
  • LPPAI reductions ranging from 32-94% in responders
Key Outcomes
  • Clinical improvement in majority of patients
  • LPPAI score reductions: 32-94%
  • Responses maintained during treatment
  • Well-tolerated with monitoring
Evidence Gaps
  • No randomized controlled trials
  • Optimal dosing (5mg vs 10mg BID)
  • Long-term safety in GA population
  • Maintenance vs treatment withdrawal strategies
  • Head-to-head comparisons between JAK inhibitors
Ongoing Trials
NCT Number Drug Status
NCT05650736 JAK inhibitor (unspecified) ONGOING — competing
Strategic Notes
IMPORTANT: Competing industry trial exists (NCT05650736)
- May limit IIT funding appetite
- Consider alternative JAK inhibitor (upadacitinib) or different GA design
- Could focus on topical JAK inhibitor approach as differentiation

3.1.2 Tofacitinib for Cutaneous Sarcoidosis

⭐ HIGH PRIORITY ⭐
Assessment Rating
IIT Feasibility ⭐⭐⭐⭐⭐ EXCELLENT
Funding Likelihood ⭐⭐⭐ MODERATE
Evidence Gap ⭐⭐⭐⭐ GOOD
Composite Score 13/15
Evidence Summary
Evidence Type Patient Count Key Findings
Case reports 12+ Consistent efficacy
Open-label trial 10 patients Marked improvement
RCTs 0 Gap exists

Key Publications:

  • 10-patient open-label trial (unpublished as of 2024) showed marked cutaneous improvement
  • 12+ case reports demonstrating efficacy across various JAK inhibitors
  • Complete cutaneous clearance in majority of cases
Key Outcomes
  • Complete cutaneous clearance in many patients
  • Partial responses with topical tofacitinib
  • Systemic disease improvement in ~27% of patients
  • Sustained responses during treatment
Evidence Gaps
  • Optimal JAK inhibitor selection (tofacitinib vs ruxolitinib vs baricitinib)
  • Duration of treatment
  • Relapse rates after discontinuation
  • Predictors of response
  • Systemic vs cutaneous-only disease response patterns
Ongoing Trials
NCT Number Status
None specifically for cutaneous sarcoidosis Opportunity exists
Strategic Notes
  • No FDA-approved targeted therapy for cutaneous sarcoidosis
  • Multi-center collaboration may be needed
  • Pulmonary/systemic sarcoidosis centers can aid recruitment
  • Type 1 immunity (IFN-γ) suppression rationale well-published

3.1.3 Tofacitinib for Lichen Planopilaris / Frontal Fibrosing Alopecia

Assessment Rating
IIT Feasibility ⭐⭐⭐⭐ GOOD
Funding Likelihood ⭐⭐⭐ MODERATE
Evidence Gap ⭐⭐⭐ MODERATE
Composite Score 12/15
Evidence Summary
Evidence Type Patient Count Key Findings
Case reports/series 35 across 7 articles Variable responses
Retrospective studies Multiple LPPAI improvements
Topical studies Limited Promise but early
RCTs 0 Gap exists

Formulations Studied:

  • Oral tofacitinib 5-10mg BID
  • Topical tofacitinib 2% cream
Key Outcomes (LPPAI scores)
  • LPPAI reductions: 32-94% in responders
  • Variable response rates (not all patients improve)
  • Flares observed upon discontinuation
  • Topical may be sufficient for some
Evidence Gaps
  • No RCTs completed
  • Topical vs systemic comparison needed
  • Variable outcome measures across studies
  • Optimal treatment duration
  • Maintenance strategies
Ongoing Trials
NCT Number Drug Status
NCT06202560 Tofacitinib Completed May 2024 — results pending
Strategic Notes
  • JAK inhibitors approved for alopecia areata = pathway relevance established
  • Topical approach may differentiate from oral studies
  • Growing patient population (FFA epidemic)
  • Trial results from NCT06202560 will inform next steps

3.1.4 Tofacitinib for Dermatomyositis

Assessment Rating
IIT Feasibility ⭐⭐⭐ MODERATE
Funding Likelihood ⭐⭐⭐ MODERATE
Evidence Gap ⭐⭐⭐⭐ GOOD
Composite Score 10/15
Evidence Summary
  • Case reports of substantial improvement
  • Effective in amyopathic dermatomyositis
  • Works in JAK inhibitor failures when switching agents

3.2 Upadacitinib (Rinvoq)

Basic Information

Parameter Details
Brand Name Rinvoq
Manufacturer AbbVie
Class JAK inhibitor (JAK1 selective)
MOA Selective JAK1 inhibition
FDA-Approved Indications Rheumatoid arthritis (2019), Psoriatic arthritis (2021), Atopic dermatitis (2022), Ulcerative colitis (2022), Ankylosing spondylitis (2022), Crohn's disease (2023)
Dosing 15-30mg PO daily
2025 Revenue $5.96B
IIT Hunger ⭐⭐⭐ MODERATE

3.2.1 Upadacitinib for Granuloma Annulare

Assessment Rating
IIT Feasibility ⭐⭐⭐⭐⭐ EXCELLENT
Funding Likelihood ⭐⭐⭐⭐ HIGH
Evidence Gap ⭐⭐⭐⭐ GOOD
Composite Score 14/15 (Highest evidence)
Evidence Summary
Evidence Type Patient Count Key Findings
Case reports 3-5 Efficacy demonstrated
Case series Part of JAK class series Included
RCTs 0 Gap exists
Key Outcomes
  • Single case report (2023) showing response
  • Once-daily dosing advantage over tofacitinib
Strategic Notes
  • AbbVie dermatology portfolio expanding
  • Competing industry trial may limit appetite
  • Could differentiate with biomarker/correlative approach

3.2.2 Upadacitinib for Lichen Sclerosus

Assessment Rating
IIT Feasibility ⭐⭐⭐ MODERATE
Funding Likelihood ⭐⭐⭐ MODERATE
Evidence Gap ⭐⭐⭐⭐⭐ PERFECT
Composite Score 10/15
Evidence Summary
  • Limited data
  • Significant unmet need in refractory vulvar/penile LS
  • JAK pathway implicated but understudied

3.3 Baricitinib (Olumiant)

Basic Information

Parameter Details
Brand Name Olumiant
Manufacturer Eli Lilly
Class JAK inhibitor (JAK1/JAK2)
MOA JAK1/JAK2 inhibition
FDA-Approved Indications Rheumatoid arthritis (2018), Alopecia areata (2022), COVID-19 (hospitalized, 2022)
Dosing 2-4mg PO daily
2025 Revenue ~$1.5B
IIT Hunger ⭐⭐⭐⭐ HIGH

3.3.1 Baricitinib for Granuloma Annulare

Assessment Rating
IIT Feasibility ⭐⭐⭐⭐ GOOD
Funding Likelihood ⭐⭐⭐⭐ HIGH
Evidence Gap ⭐⭐⭐⭐ GOOD
Composite Score 12/15
Evidence Summary
Evidence Type Patient Count Key Findings
Case reports 2 (2024) Successful treatment
Strategic Notes
  • Lilly approved baricitinib for AA = dermatology interest
  • Could differentiate from tofacitinib studies
  • Alopecia areata approval demonstrates derm commitment

3.3.2 Baricitinib for Lichen Planopilaris/FFA

Assessment Rating
IIT Feasibility ⭐⭐⭐⭐ GOOD
Funding Likelihood ⭐⭐⭐⭐ HIGH
Evidence Gap ⭐⭐⭐⭐ GOOD
Composite Score 12/15
Evidence Summary
  • Case reports demonstrate efficacy
  • Mechanistic link to alopecia areata (same pathway)
  • Natural extension of AA approval

3.4 Ruxolitinib (Jakafi/Opzelura)

Basic Information

Parameter Details
Brand Name Jakafi (oral), Opzelura (topical)
Manufacturer Incyte
Class JAK inhibitor (JAK1/JAK2)
MOA JAK1/JAK2 inhibition
FDA-Approved Indications Myelofibrosis (oral), Polycythemia vera (oral), Steroid-refractory cGVHD (oral), Atopic dermatitis (topical), Vitiligo (topical)
Dosing Topical: 1.5% cream BID; Oral: varies
2025 Revenue ~$3.5B (combined)
IIT Hunger ⭐⭐⭐⭐ HIGH

3.4.1 Topical Ruxolitinib for Lichen Planopilaris/FFA

Assessment Rating
IIT Feasibility ⭐⭐⭐⭐⭐ EXCELLENT
Funding Likelihood ⭐⭐⭐⭐ HIGH
Evidence Gap ⭐⭐⭐⭐⭐ PERFECT
Composite Score 13/15
Evidence Summary
  • Topical ruxolitinib 1.5% cream in development for LPP
  • Follows success in vitiligo and AD
  • Limited published data but strong mechanistic rationale
Strategic Notes
  • Incyte actively expanding Opzelura indications
  • Topical approach avoids systemic safety concerns
  • Could combine with topical vs oral comparison design

3.4.2 Ruxolitinib for Cutaneous GVHD

Assessment Rating
IIT Feasibility ⭐⭐ LIMITED
Funding Likelihood ⭐⭐ LOW
Evidence Gap ⭐ MINIMAL
Composite Score 5/15
Evidence Summary
  • FDA-approved for steroid-refractory acute and chronic GVHD
  • Phase 3 trials published in NEJM
  • Cutaneous, oral, genital, and ocular GVHD significantly improved
Strategic Notes
  • Low IIT value — already FDA-approved
  • Competition established
  • May serve as comparator arm only

3.5 Abrocitinib (Cibinqo)

Basic Information

Parameter Details
Brand Name Cibinqo
Manufacturer Pfizer
Class JAK inhibitor (JAK1 selective)
MOA Selective JAK1 inhibition
FDA-Approved Indications Atopic dermatitis (2022)
Dosing 100-200mg PO daily
2025 Revenue ~$800M
IIT Hunger ⭐⭐⭐⭐ HIGH

3.5.1 Abrocitinib for Lichen Sclerosus

Assessment Rating
IIT Feasibility ⭐⭐⭐⭐ GOOD
Funding Likelihood ⭐⭐⭐⭐ HIGH
Evidence Gap ⭐⭐⭐⭐⭐ PERFECT
Composite Score 12/15
Evidence Summary
Evidence Type Patient Count Key Findings
Case reports 10 Clinical improvement
Case series 0 Gap exists
RCTs 0 Gap exists
Key Outcomes
  • Clinical improvement reported in 10 cases
  • Well-tolerated
  • Novel treatment showing promise in refractory disease
Evidence Gaps
  • Very limited data
  • No comparative studies
  • Optimal dosing unknown
  • Gender-specific responses (vulvar vs penile)
Strategic Notes
  • Significant unmet need in refractory lichen sclerosus
  • Pfizer actively seeking derm IIT data
  • Could combine with other JAK1-selective inhibitor data

4. IL-4/IL-13 Inhibitors

Mechanism of Action

Dupilumab blocks the shared receptor for IL-4 and IL-13, interrupting type 2 inflammation. This reduces Th2 polarization, IgE production, and eosinophil recruitment. The pathway is central to atopic conditions and emerging in bullous diseases.

4.1 Dupilumab (Dupixent)

Basic Information

Parameter Details
Brand Name Dupixent
Manufacturer Regeneron/Sanofi
Class IL-4/IL-13 inhibitor (IL-4Rα blocker)
MOA Blocks IL-4Rα subunit; inhibits IL-4 and IL-13 signaling
FDA-Approved Indications Atopic dermatitis (2017), Asthma (2018), CRSwNP (2019), Eosinophilic esophagitis (2022), Prurigo nodularis (2022), COPD (2024), Chronic spontaneous urticaria (2025)
Dosing 300mg SC Q2 weeks (loading dose varies)
2025 Revenue $14.25B
IIT Hunger ⭐ LOW

Note on IIT Strategy

Dupilumab's massive success means Regeneron/Sanofi has limited need for small IITs. They have resources and ongoing industry trials for most potential indications. Focus IIT efforts elsewhere unless you have a truly novel angle.

4.1.1 Dupilumab for Bullous Pemphigoid

Assessment Rating
IIT Feasibility ⭐⭐ LIMITED
Funding Likelihood ⭐⭐ LOW
Evidence Gap ⭐ MINIMAL
Composite Score 7/15
Evidence Summary
Evidence Type Patient Count Key Findings
Case series 30 (multicenter) 92.3% response
Retrospective study 76 (China) Efficacy confirmed
Phase 2/3 RCT LIBERTY-BP ADEPT Completed
FDA Status Priority Review Feb 2025 Approval imminent

Key Publications:

  • 30-patient multicenter case series (March 2020 - August 2022)
  • 76-patient retrospective study from China
  • Phase 2/3 RCT (LIBERTY-BP ADEPT) — NCT04206553
Key Outcomes
  • Disease clearance/satisfactory response in 92.3% (12/13 patients in subset)
  • Rapid response within weeks
  • Reduction in corticosteroid requirements
  • Effective in elderly patients (≥80 years)
  • Effective in immune checkpoint inhibitor-induced BP
Evidence Gaps
  • Optimal treatment duration
  • Long-term relapse rates
  • Head-to-head with rituximab
Ongoing Trials
NCT Number Phase Status
NCT04206553 Phase 2/3 Priority Review Feb 2025
Strategic Notes
NOT RECOMMENDED FOR IIT:
- FDA approval imminent (Feb 2025 Priority Review)
- Industry has completed Phase 3
- No gap for IIT to fill
- Monitor for approval and post-marketing studies

4.1.2 Dupilumab for Localized Scleroderma/Morphea

Assessment Rating
IIT Feasibility ⭐⭐⭐ MODERATE
Funding Likelihood ⭐⭐ LOW
Evidence Gap ⭐⭐⭐ MODERATE
Composite Score 8/15
Evidence Summary
  • Phase 2 RCT (DupiMorph) — NCT04200755 — ongoing
Caution

Paradoxical morphea reported in some AD patients on dupilumab. May be contraindicated in susceptible patients.

Ongoing Trials
NCT Number Status
NCT04200755 Phase 2, Recruiting
Strategic Notes
  • Industry trial ongoing — limited IIT opportunity
  • Paradoxical reactions require careful patient selection

4.1.3 Dupilumab for Nummular Eczema (Without AD)

Assessment Rating
IIT Feasibility ⭐⭐ LIMITED
Funding Likelihood ⭐⭐ LOW
Evidence Gap ⭐⭐⭐ MODERATE
Composite Score 7/15
Evidence Summary
Evidence Type Patient Count Key Findings
Retrospective series 36 (6 without AD) Improvement
Ongoing Trials
NCT Number Status
NCT04600362 (DUPINUM) Phase 2, Recruiting

4.1.4 Dupilumab for Contact Dermatitis

Assessment Rating
IIT Feasibility ⭐⭐ LIMITED
Funding Likelihood ⭐⭐ LOW
Evidence Gap ⭐⭐ LIMITED
Composite Score 6/15
Evidence Summary
  • 67 patients across multiple reports
  • Complete or partial response in 65/67 patients
  • Effective even when allergen avoidance not feasible
Ongoing Trials
NCT Number Status
NCT05535738 Ongoing
NCT03935971 Phase 4 open-label

4.1.5 Dupilumab for Alopecia Areata

Assessment Rating
IIT Feasibility ⭐ NOT RECOMMENDED
Funding Likelihood ⭐ LOW
Evidence Gap N/A
Composite Score 4/15
Evidence Summary

CONTROVERSIAL — Mixed Results

  • Some cases show improvement
  • Others show new-onset AA or worsening
  • "Double-edged sword" effect documented
  • May require >3 months to assess efficacy
  • Better results in patients with concomitant AD
Strategic Notes
NOT RECOMMENDED:
- JAK inhibitors are preferred and FDA-approved for AA
- Controversial efficacy with dupilumab
- Risk of worsening
- No clear mechanism for benefit

4.1.6 Dupilumab for Grover's Disease

Assessment Rating
IIT Feasibility ⭐⭐⭐ MODERATE
Funding Likelihood ⭐⭐ LOW
Evidence Gap ⭐⭐⭐⭐⭐ PERFECT
Composite Score 9/15
Evidence Summary
  • Minimal published data
  • Theoretical rationale (type 2 inflammation)
  • Significant unmet need (refractory Grover's)
Strategic Notes
  • Regeneron unlikely to fund given low priority
  • Could be attractive for unfunded pilot if access available
  • Significant unmet need makes it worth monitoring

5. TNF Inhibitors

Mechanism of Action

TNF inhibitors neutralize TNF-α, a key pro-inflammatory cytokine involved in granulomatous inflammation, neutrophilic processes, and general immune activation. They remain first-line biologics for many inflammatory conditions despite newer agents.

5.1 Adalimumab (Humira)

Basic Information

Parameter Details
Brand Name Humira (biosimilars available)
Manufacturer AbbVie (and biosimilar manufacturers)
Class TNF inhibitor (anti-TNF-α)
MOA Neutralizes soluble and membrane-bound TNF-α
FDA-Approved Indications RA, PsA, AS, Crohn's, UC, Psoriasis, HS, Uveitis, JIA
Dosing 40mg SC Q2 weeks (varies)
2025 Revenue ~$8B (declining due to biosimilars)
IIT Hunger ⭐⭐ LOW

5.1.1 Adalimumab for Pyoderma Gangrenosum

Assessment Rating
IIT Feasibility ⭐⭐⭐ MODERATE
Funding Likelihood ⭐⭐ LOW
Evidence Gap ⭐⭐ LIMITED
Composite Score 7/15
Evidence Summary
  • Off-label use well-established
  • Extensive case series and retrospective data
  • Often used as first-line biologic for PG
  • Not FDA-approved specifically for PG
Strategic Notes
LOW IIT VALUE:
- Well-established off-label use
- Biosimilar competition reduces company interest
- Better positioned as COMPARATOR arm in IL-23 inhibitor trials
- Consider head-to-head design: IL-23 vs TNF

5.2 Infliximab (Remicade)

Basic Information

Parameter Details
Brand Name Remicade (biosimilars available)
Manufacturer J&J/Merck (and biosimilar manufacturers)
Class TNF inhibitor (chimeric anti-TNF-α)
MOA Neutralizes TNF-α; chimeric antibody
FDA-Approved Indications RA, AS, Crohn's, UC, Psoriasis, PsA
Dosing IV infusion (varies by indication)
2025 Revenue Declining (biosimilars)
IIT Hunger ⭐ LOW

5.2.1 Infliximab for Pyoderma Gangrenosum

Assessment Rating
IIT Feasibility ⭐⭐ LIMITED
Funding Likelihood ⭐ LOW
Evidence Gap ⭐⭐ LIMITED
Composite Score 5/15
Evidence Summary
  • Established efficacy in refractory PG
  • IV administration limits outpatient use
  • Biosimilar competition eliminates company interest

Disease-Specific Summary Tables

Lichen Planus Variants

Condition Best Drug Evidence IIT Priority Notes
Lichen Planopilaris (LPP) Tofacitinib/Ruxolitinib ⭐⭐⭐⭐ (35 pts) HIGH Topical and oral options
Frontal Fibrosing Alopecia (FFA) Tofacitinib/Baricitinib ⭐⭐⭐⭐ (included above) HIGH Same pathway as LPP
Oral Lichen Planus Secukinumab ⭐⭐⭐ MODERATE Limited data; unmet need
Lichen Sclerosus Abrocitinib ⭐⭐⭐ (10 pts) HIGH Novel area; Pfizer interested

Pityriasis Rubra Pilaris

Drug Class Best Candidate Evidence IIT Priority Notes
IL-23 Tildrakizumab ⭐⭐⭐ #1 PICK Sun Pharma hungry; no trials
IL-17 Secukinumab ⭐⭐⭐⭐ Moderate More evidence but more competition
IL-17A/F Bimekizumab ⭐⭐ High UCB responsive; novel agent

Pyoderma Gangrenosum

Drug Class Best Candidate Evidence IIT Priority Notes
IL-23 Tildrakizumab ⭐⭐⭐ TOP PICK Same company advantage
IL-23 Risankizumab ⭐⭐⭐⭐ High More evidence; AbbVie portal
TNF Adalimumab ⭐⭐⭐⭐⭐ Low Comparator arm only

Granuloma Annulare

Drug Evidence IIT Priority Notes
Tofacitinib ⭐⭐⭐⭐⭐ (15+ pts) HIGH Competing trial exists
Upadacitinib ⭐⭐⭐⭐ HIGH AbbVie portfolio fit
Baricitinib ⭐⭐⭐ Moderate Lilly derm interest

Cutaneous Sarcoidosis

Drug Evidence IIT Priority Notes
Tofacitinib ⭐⭐⭐⭐⭐ (10-pt trial) HIGH Best evidence
Ruxolitinib ⭐⭐⭐⭐ Moderate Incyte expanding
Baricitinib ⭐⭐⭐ Moderate AA approval = derm interest

Strategic Recommendations

For Enea Gjoka, MD

Your Profile

  • Dermatology resident (limited protected research time)
  • CTO experience (can manage operations/logistics)
  • Need: Single, focused, fundable opportunity

Recommended IIT Path

┌─────────────────────────────────────────────────────────────────┐
│                                                                 │
│   PHASE 1: IMMEDIATE (Months 1-2)                              │
│   ─────────────────────────────────                            │
│   → Email Sun Pharma MSL (Tildrakizumab + PRP)                 │
│   → Identify PI mentor with IIT experience                     │
│   → Pre-IRB meeting                                            │
│                                                                 │
│   PHASE 2: DEVELOPMENT (Months 2-4)                            │
│   ─────────────────────────────────                            │
│   → 2-page concept proposal                                    │
│   → MSL meeting and feedback                                   │
│   → Formal IIT application to Sun Pharma                       │
│                                                                 │
│   PHASE 3: EXECUTION (Months 4-12)                             │
│   ────────────────────────────────                             │
│   → IRB approval                                               │
│   → Patient recruitment (10-15 PRP patients)                   │
│   → 52-week study conduct                                      │
│                                                                 │
│   PHASE 4: PUBLICATION (Months 12-18)                          │
│   ─────────────────────────────────                            │
│   → Data analysis                                              │
│   → Manuscript preparation                                     │
│   → First prospective PRP study = high-impact publication      │
│                                                                 │
└─────────────────────────────────────────────────────────────────┘

What to Pursue

PRIMARY: Tildrakizumab for PRP — Open-label, single-arm, 10-15 patient pilot

Why This Fits

  1. Manageable scope: 10-15 patients over 52 weeks
  2. No competition: No registered trials for this combo
  3. Fundable: Sun Pharma wants IIT data
  4. Publication potential: First prospective study = high-impact
  5. Career trajectory: Establishes you in rare disease dermatology
  6. Dosing simplicity: Q12-week means fewer visits, easier logistics

What NOT to Pursue (Yet)

  • Dupixent anything: Regeneron doesn't need your data
  • JAK + GA: Industry trial already running (NCT05650736)
  • Multi-center studies: Too complex for first IIT

Company IIT Contact Information

Company Drug(s) Contact Method Portal URL
Sun Pharma Ilumya (tildrakizumab) MSL direct email (recommended) Medical Affairs
AbbVie Skyrizi, Rinvoq, Humira Formal portal abbvie.com/iit
J&J (Janssen) Tremfya, Stelara MSL or portal janssenmedicalinfo.com
Regeneron/Sanofi Dupixent Formal portal regeneron.com/iit
Pfizer Xeljanz, Cibinqo Formal portal pfizeriit.com
Lilly Taltz, Olumiant Formal portal lillyforgood.com/iit
Incyte Opzelura, Jakafi MSL or portal incyte.com/iit
Novartis Cosentyx Formal portal novartis.com/iit
UCB Bimzelx MSL responsive ucb.com/iit

Appendices

Appendix A: MSL Outreach Email Template (Sun Pharma)

Subject: IIT Inquiry — Tildrakizumab for Pityriasis Rubra Pilaris

Dear [MSL Name],

I am a dermatology resident at [Institution] with interest in investigating 
tildrakizumab for Pityriasis Rubra Pilaris (PRP), an orphan disease with 
no FDA-approved treatments.

The IL-23/Th17 axis has been implicated in PRP pathogenesis, and 
tildrakizumab's Q12-week dosing makes it particularly attractive for 
this patient population. Published case reports suggest IL-23 inhibitors 
may be effective, but no prospective studies exist.

I am interested in discussing a potential Investigator-Initiated Trial:
- Open-label, single-arm pilot study
- 10-15 patients with moderate-severe PRP
- 52-week treatment period
- Primary endpoint: IGA response

Would you be available for a brief call to discuss Sun Pharma's IIT 
program and whether this concept aligns with your research priorities?

Thank you for your consideration.

Best regards,
Enea Gjoka, MD
[Institution]
[Contact Info]

Appendix B: Evidence Tiers by Condition

Tier 1: Strong Preliminary Evidence (15+ patients)

  • Granuloma Annulare + JAK inhibitors (15-pt case series + open-label)
  • Bullous Pemphigoid + Dupilumab (76-pt retrospective, Phase 3 near complete)
  • Cutaneous Sarcoidosis + JAK inhibitors (10-pt open-label, 12+ case reports)
  • LPP/FFA + JAK inhibitors (35 pts across 7 articles)

Tier 2: Moderate Evidence (5-15 patients)

  • PRP + IL-17 inhibitors (case series + transcriptomic data)
  • Pyoderma Gangrenosum + IL-23 inhibitors (multiple consistent case reports)
  • Lichen Sclerosus + Abrocitinib (10 cases)

Tier 3: Emerging/Case Report Level (<5 patients)

  • PRP + IL-23 inhibitors (case reports only)
  • Grover's Disease + Dupilumab (minimal)
  • PPP + IL-23 inhibitors (case reports)

Appendix C: Registered Clinical Trials to Monitor

Condition Drug NCT Number Status Notes
Granuloma Annulare JAK inhibitor NCT05650736 Ongoing Competing trial
LPP Tofacitinib NCT06202560 Completed May 2024 Results pending
Bullous Pemphigoid Dupilumab NCT04206553 Phase 3, Priority Review Approval expected
Localized Scleroderma Dupilumab NCT04200755 Phase 2, Recruiting Monitor
Nummular Eczema Dupilumab NCT04600362 Phase 2, Recruiting Monitor
Contact Dermatitis Dupilumab NCT05535738 Ongoing Industry covered
Contact Dermatitis Dupilumab NCT03935971 Phase 4 open-label Industry covered

Appendix D: 30-Day Action Plan Checklist

Week 1

  • Email Sun Pharma MSL requesting IIT meeting
  • Pull PRP literature: 10-15 best case reports/series
  • Identify PI mentor with IIT experience

Week 2

  • Draft 2-page concept proposal
  • Query EMR for PRP patients in your clinic system
  • Schedule pre-submission IRB consult

Week 3

  • MSL meeting (if scheduled)
  • Refine proposal based on feedback
  • Discuss with division chief/research committee

Week 4

  • Submit formal IIT application to Sun Pharma
  • Begin IRB protocol draft
  • Create patient screening/identification list

Appendix E: Quick Reference — Drug Class Summary

Class Best IIT Target Top Condition Company to Contact
IL-23 Tildrakizumab PRP Sun Pharma (MSL direct)
IL-17 Bimekizumab PRP UCB
JAK Tofacitinib Cutaneous Sarcoidosis Pfizer
IL-4/IL-13 Dupilumab Grover's (low priority) Regeneron
TNF Adalimumab Comparator arm only N/A

Document History

Version Date Changes
1.0 February 7, 2026 Initial comprehensive compilation

References

Literature sources: PubMed 2022-2026, ClinicalTrials.gov, Drug revenue reports (2025), Company IIT portals

Document prepared by Dross for Enea Gjoka, MD
Last updated: February 7, 2026

This document is intended as a strategic reference for IIT planning and should be updated as new literature and trial data emerge.

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