Immunovant, Inc. · NASDAQ:IMVT
Immunovant — LifeSci Capital Fireside Chat (December 2022)
32 slides from Immunovant's conference presentation, Dec 8, 2022
Slide 1: LifeSci Capital Fireside Chat
LifeSci Capital Fireside Chat December 8, 2022 Exhibit 99.1
Slide 2: Forward-looking statements
Forward-looking statements 2 This presentation contains forward-looking statements for the purposes of the safe harbor provisions under The Private Securities Litigation Reform Act of 1995 and other federal securities laws. The use of words such as "can," “may,” “might,” “will,” “would,” “should,” “
Slide 3: Building a leading anti-FcRn franchise to address unmet need
Building a leading anti-FcRn franchise to address unmet need 3 Multiple paths to potential value creation with batoclimab and IMVT-1402 Based on clinical development achievements to date in MG, we have incurred a $10M milestone payment obligation to HanAll in CYQ4 2022 which was already considered i
Slide 4: Today's agenda/discussion topics
Today’s agenda/discussion topics 4 Overview of the neonatal Fc receptor (FcRn) Anti-FcRn antibody basics – structure, affinity, etc. Translatability of albumin and LDL signals from non-human primates to humans Correlation of IgG reduction and clinical efficacy in autoimmune diseases CIDP trial desig
Slide 5: + + + + + + + + + * 2, + + +
+ + + + + + + + + * 2, + + + + + + oe + + + + + NOVANT + Yf immu
Slide 6: IgG autoantibodies cause disease pathology directly or via immune complexes
For some autoimmune diseases, IgG autoantibodies cause disease pathology directly or via immune complexes IgG autoantibodies can be directly pathogenic IgG autoantibodies may also lead to pathogenic immune complexes Characteristics • In ‘classic’ auto-antibody mediated diseases, auto- antibodies ten
Slide 7: FcRn promotes recycling of IgG antibodies
The neonatal Fc receptor (FcRn) promotes recycling of IgG antibodies 7 FcRn Mechanism of Action 1. IgG is taken up into cells in endocytic vesicle 2. FcRn-IgG complexes are sorted from unbound proteins 3. Unbound proteins are trafficked to lysosome for degradation 4. IgG is recycled back into circul
Slide 8: FcRn inhibition promotes IgG degradation
Blood Endocytic vesicle Endosome LysosomeMonocyte or endothelial cell Key: Serum proteinIgG FcRn 1 2 3 4 FcRn inhibition promotes IgG degradation 8 Mechanism of Action of FcRn Inhibition 1. IgG and FcRn inhibitor are taken up into cells in endocytic vesicles 2. FcRn inhibitor binds to FcRn in endoso
Slide 9: + + + + + + + + + ey * FcRn Inhibitor ce
+ + + + + + + + + ey * FcRn Inhibitor ce + A + + A + + oe + i. + + + + NOVANT + Yf immu
Slide 10: Anti-FcRn assets have unique characteristics
Anti-FcRn assets have unique characteristics No clinical head-to-head comparisons of Immunovant product candidates and third party anti-FcRn assets has been conducted. Binding affinities are SPR Sources: 1. On file at Immunovant; 2. Ulrichts 2018; 3.Ling, 2019 (ASH 2015 poster); 4.Smith, 2018; Kiess
Slide 11: Fc portion of IgG and albumin have different binding sites on FcRn
The Fc portion of endogenous IgG (Fc) and albumin have different binding sites on the FcRn 11 Albumin FcRn Fc FcRn Albumin FcRn Fc For Investor Audiences Only
Slide 12: Batoclimab-FcRn complex orients differently from IMVT-1402-FcRn complex
Co-crystallization shows that the batoclimab-FcRn complex orients differently from the IMVT 1402-FcRn complex 12Note: Ribbon representations generated from X-Ray co-crystal structure. Batoclimab solved at 2.4Å resolution. IMVT-1402 solved at 2.6Å resolution. Batoclimab FcRn FcRn IMVT-1402 Albumin Fc
Slide 13: Co-crystal structures for IMVT-1402, efgartigimod and SYNT001 with FcRn
Co-crystal structures for IMVT-1402, for efgartigimod and for SYNT001 all with FcRn 13 FcRn SYNT001 IMVT-1402 Efgartigimod* SYNT001** FcRn IMVT-1402 *https://www.rcsb.org/structure/7Q15; **Blumberg et al., Sci. Adv. 2019 Dec 18;5(12):eaax9586. FcRn Efgartigimod Note that orientation of FcRn is shown
Slide 14: IMVT-1402 selected for maximum IgG reduction while minimizing albumin interference
IMVT-1402 was selected to deliver maximum IgG reduction while minimizing interference with the albumin recycling Batoclimab: overlay with albumin and FcIMVT-1402: overlay with albumin and Fc 14Note: Ribbon representations generated from X-Ray crystal structure. Batoclimab solved at 2.4Å resolution.
Slide 15: Translatability of data from cynomolgus monkey to humans
Translatability of data from cynomolgus monkey to humans 15
Slide 16: IMVT-1402 and placebo demonstrated similar albumin and LDL
16 IMVT-1402 and placebo demonstrated similar albumin and LDL Day SD, standard deviation; ULN, upper limit of normal; LLN, lower limit of normal; Arrows indicate time of dosing. Data on file at Immunovant Day Batoclimab 50 mg/kg (n=3) IMVT-1402 50 mg/kg (n=7) IMVT-1402 5 mg/kg (n=7) Placebo (n=3) LD
Slide 17: Albumin impact in non-human primates highly translatable to humans
Impact on albumin observed in non-human primates has been highly translatable to humans 17 1. Ulrichts P.J Clin Invest. 2018 Oct 1;128(10):4372-4386 2. Efgartigimod EMA assessment report - EMA/641081/2022 3. Efgartigimod FDA integrated review - 761195Orig1s000 4. Blumberg LJ. Sci Adv. 2019 Dec 18;5(
Slide 18: IgG Reduction and Clinical Efficacy
IgG Reduction and Clinical Efficacy 18
Slide 19: IMVT-1402 and batoclimab demonstrated similar maximum IgG reduction
-100 -50 0 50 100 0 7 14 21 28 35 42 56 • 20 monkeys, dosed IV in head-to-head study across four groups • At comparable doses, IgG lowering is similar for both batoclimab and IMVT-1402 • Cynomolgus monkeys observed to be reliable pharmacodynamic proxy for anti-FcRn mediated impacts on IgG1,2 IMVT-14
Slide 20: Clinical data in MG show correlation between deep IgG reduction and efficacy
Clinical data in MG across anti-FcRn assets indicate strong correlation between deep IgG reduction and increased clinical efficacy The ADAPT Phase 3 trial of IV efgartigimod demonstrated that patients with deeper IgG reductions saw greater improvements in their disease activity (MG-ADL) compared to
Slide 21: Other autoantibody-driven indications show correlation between IgG reduction and efficacy
Clinical data in multiple other autoantibody-driven indications suggest strong correlation between IgG reduction and clinical efficacy Immunovant’s Phase 2 trial in TED indicated that reduction in IgG led to greater restoration of normal levels of pathogenic Abs and greater proptosis response rates
Slide 22: Efgartigimod IgG reduction in pemphigus vulgaris
64% 62% 66% 0% 20% 40% 60% 80% 100% Efgartigimod IV Efgartigimod IV Efgartigimod SC Mean IgG Lowering from Baseline ITP MG MG Efgartigimod Dosage Median IgG Reduction (Day 29) 10 mg / kg (approved dose) 62% 25 mg / kg 66% Efgartigimod IgG Reduction in Pemphigus Vulgaris ARGX IV: 10 mg/kg recommended
Slide 23: Greater IgG reduction leads to greater efficacy across programs
Consistent evidence across all programs and all indicators that greater IgG reduction leads to greater efficacy Company Evidence of Greater IgG Reductions Translating to Clinical Benefit M G T E D IT P Greater IgG reductions across arms ➔ greater anti-AChR autoantibody reductions and greater MG-ADL
Slide 24: Batoclimab and IMVT-1402 unique product attributes among anti-FcRn assets
Batoclimab and IMVT-1402’s unique product attributes amongst anti- FcRn assets provide significant potential impact to patient experience 1. ARGX MG PH3 IV, SC 2. Except as initial approvals in MG and ITP, which will be IV 10mg/kg QW 3. Estimated as pivotal trial dose of 30mg/kg IV loading dose foll
Slide 25: De-risking CIDP Trial with Unique Design
De-risking CIDP Trial with Unique Design 25
Slide 26: CIDP represents an exciting opportunity
CIDP represents an exciting opportunity Sources: 1. Broers M, et al (2019) Incidence and prevalence of CIDP: a systematic review and meta-analysis. Neuroepidemiology 52(3– 4):161–172; 2. Querol, L., et al. Systematic literature review of burden of illness in chronic inflammatory demyelinating polyne
Slide 27: Response to IVIG and plasma exchange supports anti-FcRn mechanism
Response to current treatments of IVIG and Plasma Exchange creates strong rationale for potential benefit of anti-FcRn mechanism axon Myelin Sheath (produced by Schwann cells) anti-myelinated peripheral nerve IgG in 30-40% patients1 autoantibodies neuron CIDP is characterized by predominant demyelin
Slide 28: Anti-FcRn mechanism of action may protect myelin sheath in CIDP
Anti-FcRn mechanism of action degrades IgG, potentially protecting the myelin sheath from pathogenic IgG autoantibody attack in CIDP 28 Endothelial Cell Myelin Sheath In the absence of batoclimab, FcRn binds to the IgG autoantibodies, inhibiting their degradation and returning them into circulation.
Slide 29: Development approach applies learnings from historical CIDP trials
Our development approach applies key learnings from historical and ongoing CIDP trials to address challenges unique to CIDP 29 Trial risks Mitigations Mitigation included in other anti-FcRn Trials* Mitigation included in IMVT trial Disease heterogeneity and challenging diagnosis Diagnostic algorithm
Slide 30: CIDP pivotal Phase 2b trial design
CIDP pivotal Phase 2b trial design intended to enable development of potentially best-in-anti-FcRn-class chronic therapy for CIDP A: Cohorts are defined by CIDP treatment at Screening., B: Participants who fail to worsen by Week 0 will be withdrawn from the study at Week 0., C: Period 1 Non-Responde
Slide 31: Differentiated approach to developing batoclimab as chronic CIDP treatment
Immunovant pursuing a differentiated approach to developing batoclimab as a chronic treatment for CIDP 31 CIDP is an exciting indication that is ripe for disruption Our pivotal study is optimized versus historical and current studies Batoclimab has potential best-in-class efficacy and could be first
Slide 32: Thank You
Thank: You + ay Sr as op me fa ap S552 45 + me! a + + \f IMMUNOVANT
Immunovant — LifeSci Capital Fireside Chat (December 2022) on 6ix