Inhibrx Biosciences, Inc. · NASDAQ:INBX
Inhibrx Biosciences — Investor Presentation (August 2023)
36 slides from Inhibrx Biosciences's investor presentation, August 2023
Slide 1: INBX Investor Presentation
INBX Investor Presentation Innovation Driven Outcomes Focused August 2023
Slide 2: Presentation disclaimer
Presentation disclaimer This presentation contains forward-looking statements. In some cases, you can identify The Company may not actually achieve the plans, intentions or expectations disclosed forward-looking statements by the words “will,” “expect,” “intend,” “plan,” “objective,” in its forward-
Slide 3: Company overview
Company overview Founded in 2010 $192.5M > 30% Key Financial Cash and cash equivalents First IND in 2018 Internal ownership Highlights: IPO in 2020 (as of 6/30/2023) 43.7M 50.8M Common stock outstanding Fully diluted outstanding 165+ Partnerships with Industry employees with an experienced leadershi
Slide 4: Inhibrx's innovative approach to therapeutic discovery
Inhibrx’s innovative approach to therapeutic discovery Our core belief: Our technology and protein engineering expertise enables us to efficiently identify optimal therapeutic formats bespoke to the target biology. Modular protein Rapid and iterative Therapeutics tailored engineering platforms optim
Slide 5: Pipeline
Pipeline Preclinical Phase 1 Phase 2 Phase 3 Registration Study INBRX-109 Precisely engineered valency to mediate optimal balance of efficacy and safety tetravalent Registration-enabling study in DR5 agonist chondrosarcoma underway Robust OX40 agonist superior to bivalent antibodies INBRX-106 Promis
Slide 6: Near term expected clinical milestones
Near term expected clinical milestones INBRX-109 (DR5) Initial mesothelioma, Ewing INBRX-109 sarcoma, colorectal cancer and GIST (DR5) Registration-enabling combination study data Phase 2 Chondrosarcoma data INBRX-101 INBRX-101 (AATD) Initial readout (GvHD) Trial initiations from ElevAATe study for
Slide 7: INBRX-101 AATD
Goal: To develop a donor-independent source of AAT protein able to keep patients in the range of normal for AAT extended periods of time Recombinant AAT protein INBRX-101 AATD recombinant Alpha-1 antitrypsin Fc-fusion Plasma Donor protein (AAT-Fc) derived AAT protein Current SOC Inhibrx solution
Slide 8: INBRX-101 for the treatment of alpha-1 antitrypsin (AAT) deficiency (AATD)
INBRX-101 for the treatment INBRX-101 of alpha-1 antitrypsin (AAT) deficiency (AATD) Disease background ZZ Current standard of care Pi*Z and PI*S alleles cause the AATD is an inherited rare disease of the lungs and liver (~15% of cases) characterized by majority of severe AATD cases Weekly augmentat
Slide 9: INBRX-101 for the treatment of AATD
INBRX-101 for the treatment of AATD INBRX-101 INBRX-101 is a precisly engineered INBRX-101 recombinant human AAT-Fc fusion protein characteristics: AAT Sustainable Not dependent supply on plasma donation two recombinant human AAT proteins Oxidation- Prevents loss prone residues of activity in the lu
Slide 10: INBRX-101: phase 1 study design
INBRX-101: phase 1 study design INBRX-101 INBRX-101 phase 1 study: open-label, multicenter, dose-escalating study Eligibility Part 1 Part 2 Parts 1 and 2: Single ascending Multiple ascending dose (SAD) dose escalation (MAD) Primary Adult patients with AATD, Complete Complete endpoint: regardless of
Slide 11: Topline results from phase 1, part 2: INBRX-101
Topline results from phase 1, part 2 INBRX-101 Parts 2: INBRX-101 topline results – 3rd dose of 40, 80 or 120 mg/kg (Q3W): Favorable safety 100 and tolerability profile 120 mg/kg MAD cohorts demonstrate observed with only mild and 80 mg/kg Functional AAT levels (μM) 80 Cavg of functional AAT of 37.6
Slide 12: INBRX-101 is present in the lung in every patient sampled
INBRX-101 is present in the lung in every patient sampled INBRX-101 following IV dosing suggesting penetration to target organ Bronchoalveolar lavage fluid (BALF) sample collection and analysis BALF samples were collected from 3 lobes of the lung for each patient in the 80 (N = 5) 200 and 120 (N = 6
Slide 13: Modeled phase 3 dose of 120 mg/kg Q4W achieves AAT normal range
Modeled phase 2 dose of 120 mg/kg Q4W achieves AAT normal range INBRX-101 Projected mean steady-state functional AAT levels 80 pdAAT is only projected to achieve normal functional AAT levels for 2 – 2.5 days per weekly dose in Functional AAT levels (μM) 60 AATD patients (9/28 days per month). INBRX-
Slide 14: INBRX-101 AATD registration-enabling trial
INBRX-101 AATD registration-enabling trial INBRX-101 Study INBRX101-01-201: ElevAATe + Randomized, active controlled, INBRX-101 at 120 mg/kg Q3W & placebo N=36 double-blind on non-dosing weeks Main Eligibility Criteria Initiated + Adult patients aged 18-80 + Head-to-head superiority study: with AATD
Slide 15: INBRX-101: AATD market opportunity
INBRX-101: AATD market opportunity INBRX-101 TODAY FUTURE Severe* AATD cases US prevalence ~100K ~100K *defined as <11 μM serum AAT levels ̴40K Upside market potential Total treated US patients ̴8K–10K from continued increased rate of diagnosis and a focus on earlier prevention of lung loss ZZ SZ US
Slide 16: Clinical data and established guidelines exist for AAT therapy in acute GvHD
Clinical data and established guidelines INBRX-101 exist for AAT therapy in acute GvHD Existing clinical data for Jakafi: Existing clinical data for Current standard of care plasma-derived AAT therapies Active Phase 2/3 studies sponsored by CSL 2L (steroid resistant) acute GVHD (aGVHD) 2L (steroid r
Slide 17: INBRX-109
Goal: To develop a more precise DR5 agonist able to selectively induce apoptosis in tumor cells Empirically selected tetravalent DR5 agonist that restricts INBRX-109 unwanted secondary clustering tetravalent DR5 agonist DR5 agonists with limited on target effect or unwanted off tumor toxicity Previo
Slide 18: INBRX-109: a next generation DR5 agonist with an optimized balance of efficacy and safety
INBRX-109: a next generation DR5 agonist INBRX-109 with an optimized balance of efficacy and safety Death Receptor 5 (DR5 / TRAIL-R2) is highly expressed on INBRX-109 tumorigenic, transformed or damaged cells but not normal cells, characteristics: making DR5 a promising therapeutic target in oncolog
Slide 19: INBRX-109 is a potent inducer of extrinsic cell death via the DR5 pathway
INBRX-109 is a potent inducer of extrinsic cell death via the DR5 pathway INBRX-109 TRAIL INBRX-109 DR5 DR5 DR5 FADD FADD FADD Tumor cell Caspase activation Tumor cell Caspase activation Tumor cell Caspase activation Apoptosis moderate strong Apoptosis Apoptosis DR5 (TRAIL-R2) is a pro-apoptotic rec
Slide 20: INBRX-109 is precision-engineered for optimal potency and safety
INBRX-109 is precision-engineered for optimal potency and safety INBRX-109 Valency drives both DR5-induced tumor cell death and hepatocyte destruction Impact of valency on DR5-mediated cell death Impact of valency on hepatotoxicity Impact of valency on cell death: Impact of valency on cell death: In
Slide 21: INBRX-109: Phase 1 trial design
INBRX-109: Phase 1 trial design INBRX-109 Study of INBRX-109 in patients with locally advanced or metastatic solid tumors, including sarcomas Part 1 Part 2 Part 3 INBRX-109 single-agent Complete INBRX 109 single-agent Ongoing Dose expansion Ongoing dose escalation dose expansion with chemotherapy N=
Slide 22: Encouraging mPFS and clinical responses observed in Chondrosarcoma patients
Encouraging mPFS and clinical responses observed in INBRX-109 Chondrosarcoma patients treated with INBRX-109 Impact of valency on DR5-mediated cell death Selected case reports PFS by Kaplan-Meier analysis Partial March 4, 2020 (baseline) September 3, 2020 (-61%) response: Overall median PFS: 7.6 mon
Slide 23: INBRX-109 Phase 2 Registration Enabling Study
INBRX-109 Phase 2 Registration Enabling Study INBRX-109 Patients Conventional chondrosarcoma, Grades 2 and 3, unresectable or metastatic Randomization stratified by line of therapy, Grade and IDH1/2 R Primary endpoint: mutation status 2:1 Progression free survival INBRX-109 Placebo Secondary endpoin
Slide 24: INBRX-106
Goal: To develop a potent OX40 agonist able to induce robust signal activation strong Hexavalent OX40 agonist with enhanced INBRX-106 clustering/signaling hexavalent OX40 agonist weak Bivalent OX40 agonists elicit weak downstream signals with limited clinical activity Previous generation Inhibrx sol
Slide 25: INBRX-106: generating robust OX40 signaling to drive anti-tumor activity
INBRX-106: generating robust OX40 signaling to drive anti-tumor activity INBRX-106 INBRX-106 is designed to boost anti-tumor T-cell activity by INBRX-106 potently activating the OX40 co-stimulatory pathway characteristics: Simultaneously engage multiple Six OX40 Stimulation T NK Hexavalent OX40 to d
Slide 26: INBRX-106: mechanism of action
INBRX-106: mechanism of action INBRX-106 Effective OX40 agonism potentiates the body’s immune response towards a tumor T cell ↑ T cell TT cells cells TT ↑OX40 OX40 NK NK cells cells NK NK TCR TCR antigen antigen INBRX-106 Tumor MHC MHC Monocytes Monocytes Dendritic cell Tumor cell Tumor cell The T-C
Slide 27: Higher OX40 valency drives superior T cell activation and reduces Treg suppression
Higher OX40 valency drives superior T cell activation and reduces Treg INBRX-106 suppression CD4 T Cell Co-Stimulation1 Reversal of Treg Suppression2 ~2-fold increase vs bi-valent and untreated CD8 T Cell Co-Stimulation1 + Hexavalent INBRX-106 engagement drives superior co- stimulation of both CD4 a
Slide 28: Valency drives OX40 agonism in CPI-resistant tumor models
Valency drives OX40 agonism in CPI-resistant tumor models INBRX-106 Syngeneic B16F10 Mouse Tumor Model Vehicle Bivalent OX40 mAb Hexavalent INBRX-106-a* 0/10 CRs 0/10 CRs 3/10 CRs Anti-PD1 Alone Anti-PD1 + Bivalent OX40 mAb Anti-PD1 + Hexavalent INBRX-106-a* 0/10 CRs 1/10 CRs 6/10 CRs • OX40 agonism
Slide 29: INBRX-106 study design
INBRX-106 study design INBRX-106 Phase 1/2 study of single agent INBRX-106 and INBRX-106 in combination with pembrolizumab in patients with locally advanced or metastatic solid tumors Part 1 Part 2 Part 3 Part 4 Complete Ongoing Complete Ongoing Durable responses INBRX-106 INBRX-106 Dose expansion D
Slide 30: INBRX-105
Goal: Restrict potent 4-1BB agonism to areas of high PD-L1 expression Localized 4-1BB agonist specific INBRX-105 to PD-L1+ tissues tetravalent PD-L1 targeted 4-1BB agonist Indiscriminate 4-1BB activation leads to a narrow therapeutic window limited by hepatotoxicity Previous generation therapy Inhib
Slide 31: INBRX-105: localizing and potentiating the anti-cancer effects of the 4-1BB pathway
INBRX-105: localizing and potentiating INBRX-105 the anti-cancer effects of the 4-1BB pathway INBRX-105 designed to boost anti-tumor INBRX-105 T-cell activity in PD-L1 expressing tissues characteristics: Bispecific/ Designed to co-engage PD-L1 T and 4-1BB in order to confer Conditional PD-L1 depende
Slide 32: INBRX-105 mechanism of action
INBRX-105 mechanism of action INBRX-105 PD-L1 targeted 4-1BB agonism amplifies anti-tumor response and localizes T-cell activity T cell ↑ T cell ↑4-1BB 4-1BB T cells T TCR TCR antigen antigen INBRX-105 Tumor MHC MHC PD-L1 PD-L1 NK cells NK Tumor cell Tumor cell The T-Cell Receptor (TCR) recognizes B
Slide 33: INBRX-105 shows improved T cell modulation over PD-L1 and 4-1BB agents
INBRX-105 shows improved T cell modulation INBRX-105 over PD-L1 and 4-1BB agents alone or in combination T Cell Co-stimulation1 T Cell Co-stimulation2 Peptide-induced TCR signal MHC mismatch-induced TCR signal Co-stimulation with 80 10 INBRX-105 INBRX-105 following Urelumab* TCR engagement yields At
Slide 34: Localizing 4-1BB agonism to the PD-L1-rich tumor microenvironment
Localizing 4-1BB agonism to the PD-L1-rich tumor microenvironment INBRX-105 leads to potent anti-tumor activity in mouse models Enhanced T Cell Infiltration to TME MC38: Day 7 PD-L1+ Tumor Model1 Dramatic increase 6 2000 in T cell frequency in the T cell frequency - fold change over vehicle tumor mi
Slide 35: INBRX-105 study design
INBRX-105 study design INBRX-105 An open-Label, multicenter, dose-escalation, Phase 1/2 study of INBRX-105 and INBRX-105 in combination with pembrolizumab in patients with locally advanced or metastatic solid tumors Part 1 Part 2 Part 3 Part 4 Single agent Complete Single agent Dose escalation Compl
Slide 36: Investor Relations
Investor Relations: Kelly Deck, CPA CFO 11025 N. Torrey Pines Road Suite 200 La Jolla, CA 92037 Office: 858.795.4260 [email protected]
Inhibrx Biosciences — Investor Presentation (August 2023) on 6ix