Bioinvent International Ab · OMXSTO:BINV
Bioinvent International Ab — Investor Day (December 2022)
59 slides from Bioinvent International Ab's investor day presentation, Dec 8, 2022
Slide 1: Unleashing Immunity to Fight Cancer
UNLEASHING IMMUNITY TO FIGHT CANCER Function first drug discovery 1 │1 │
Slide 2: Forward-Looking Statement
FORWARD-LOOKING STATEMENT This presentation does not constitute or form part of any offer or invitation to purchase or subscribe for, or any offer to underwrite or otherwise acquire, any shares or any other securities in BioInvent International AB (“BioInvent”). Neither shall the presentation or any
Slide 3: Agenda BioInvent R&D Day December 8, 2022
AGENDA BIOINVENT R&D DAY DECEMBER 8, 2022 Moderator Lars Frick, journalist Börsveckan 2:00 PM Welcome & introduction Martin Welschof, CEO Björn Frendéus, CSO 2:10 PM FcyRIIB clinical programs, BI-1206 and BI-1607 Andres McAllister, CMO 3:00 PM Break Björn Frendéus, CSO 3:15 PM The oncolytic drug can
Slide 4: Today's Presenters
TODAY’S PRESENTERS Dr Sean Lim Andres McAllister, CMO Björn Frendéus, CSO Martin Welschof, CEO Associate Professor and Honorary CMO BioInvent since 2017 CSO BioInvent since 2014 CEO BioInvent since 2018 Consultant in Hematological Previously CSO at Debiopharm; Graduated from the Swedish Previously D
Slide 5: Immune-checkpoint inhibitors heralded a new era in cancer treatment
The development of immune-checkpoint inhibitors has heralded a new era in cancer treatment, enabling the possibility of long-term survival in patients with metastatic disease, and providing new therapeutic indications in earlier- stage settings. Nature Reviews Clinical Oncology volume 19, pages254–2
Slide 6: Immune checkpoint inhibitors have become the standard of care
Immune checkpoint Half of all patients with metastatic inhibitors have cancer are eligible in economically developed countries become the standard of care for several Eight approved agents are available types of solid cancer for 17 different malignancies 5,000+ clinical trials are ongoing for PD-1/P
Slide 7: We are not there yet
The number of targets available for We are not antibody therapy is still limited there yet And most of these targets have failed to deliver therapies that work in the clinic The majority of patients do not respond at all, or their response is short-lived due to rapidly evolving resistance 7 │
Slide 8: What if we turned the drug discovery process around
What if we turned the drug discovery process around, to start from what matters the most? 8 │
Slide 9: Function F.I.R.S.T Drug Discovery
FUNCTION F.I.R.S.T™ DRUG DISCOVERY TUMOR While others often focus on the BioInvent’s targets and test function at the end, FUNCTION FUNCTION FIRST We start from the function DRUG DISCOVERY TARGET SELECTION 9 │
Slide 10: Highly Integrated Company, Strong Competitive Advantage
HIGHLY INTEGRATED COMPANY STRONG COMPETITIVE ADVANTAGE Smart Translation Into the Clinic Strong Team with Unique Antibody Experience Cutting Edge Technical Science and Operations Discovery and CMC Engine Capabilities 10 │
Slide 11: Strong Pipeline with Multiple Value Drivers
STRONG PIPELINE WITH MULTIPLE VALUE DRIVERS 11 │
Slide 12: Clinical Pipeline
Clinical Pipeline : Biolnvent
Slide 13: Overcoming the Resistant Tumor Microenvironment
OVERCOMING THE RESISTANT TUMOR MICROENVIRONMENT • Many cancer patients do not respond or develop resistance to immunotherapy • New drugs and mechanisms of action that help activate robust anti-cancer immunity are needed INFLAMED NONINFLAMED Preexisting Immunity Excluded Infiltrate Immunologically Ig
Slide 14: Function F.I.R.S.T Discovery of New Oncology Targets and Antibodies
FUNCTION F.I.R.S.T™ DISCOVERY OF NEW ONCOLOGY TARGETS AND ANTIBODIES 14 │
Slide 15: Powerful Targets and Antibody Mechanisms-of-Action
POWERFUL TARGETS AND ANTIBODY MECHANISMS-OF-ACTION Target BI-1206 BI-1607 BI-1808 BI-1910 BT-001 (Vectorized aCTLA-4) 15 │
Slide 16: aFcgRIIB - BI-1206 & BI-1607
oFcyrlIB - BI-1206 & BI-1607 : Biolnvent
Slide 17: Executive Summary – anti-FcgRIIB (BI-1206 & BI-1607)
EXECUTIVE SUMMARY – anti-FcgRIIB (BI-1206 & BI-1607) • Fcg receptors, “the antibody checkpoints” modulate the efficacy of IgG antibodies – Inhibitory receptors (CTLA-4, PD-1/PD-L1) – Immune agonist receptors (ox40, 4-1BB, GITR, CD40) – Other receptors (IL-2R) • FcgRIIB is the sole inhibitory FcgR •
Slide 18: BI-1206 (aFcgRIIB)
BI-1206 (aFcyRIIB) "e"B iolnvent
Slide 19: BI-1206 in NHL – Overcoming Rituximab Resistance
BI-1206 IN NHL – OVERCOMING RITUXIMAB RESISTANCE 19 │
Slide 20: BI-1206 Boosts Efficacy and Overcomes Rituximab Resistance
BI-1206 BOOSTS EFFICACY AND OVERCOMES RITUXIMAB RESISTANCE BI-1206 Blocks Rituximab Internalization And Improves Its Anti-tumor Activity B cell depletion in vivo BOOSTING RITUXIMAB’S EFFECT OVERCOMING RESISTANCE % objective responders (blue) Human CD20 FcγRIIB double transgenic mice Humanized model
Slide 21: High Expression of FcgRIIB Correlates with Poor Prognosis
HIGH EXPRESSION OF FcgRIIB CORRELATES WITH POOR PROGNOSIS Mantle cell lymphoma Follicular lymphoma Diffuse Large B cell Lymphoma - + FcgRIIb FcgRIIb Lim, Blood, 2011 21 │ Lee, Br J Hematol, 2014
Slide 22: BI-1206 in Combination with Rituximab: Phase 1/2a Study
BI-1206 IN COMBINATION WITH RITUXIMAB: OPEN LABEL PHASE 1/2a STUDY Ongoing phase STUDY OVERVIEW Part A Part B BI-1206 + RTX1 BI-1206 + RTX1 Patients 3+3 dose escalation Expansion phase 2a (n=9-12) END of (n=12) with: relapsed or 4 weekly doses followed PHASE 1 4 weekly doses followed by maintenance,
Slide 23: * These patients are still on CR after > 2 and 3 years after
* * Implementation of Protocol * These patients are still on CR after amendment > 2 and 3 years after the EoT. The New steroid third patient was lost to follow up, regimen hence we do not have the information **4 patients were dosed at 200 mg split dose ** *** Patient 006-004 is entering *** Mainten
Slide 24: BI-1206-02 Time on Study & Tumor Change in Follicular Lymphoma
BI-1206-02 TIME ON STUDY & TUMOR CHANGE (%) IN FOLLICULAR LYMPHOMA SUBSET 24 │
Slide 25: BI-1206-02 Dose Escalation
BI-1206-02 DOSE ESCALATION Split-dosing Cohort No. 6 4 patients 200 mg Cohort Cohort No. No.22 Cohort No. 5 Expansion cohort I.V. (2 (2 patients) patients) 3 patients 1 patient ongoing 100 100 mgmg 100 mg 100 mg 2 DLTs Cohort No. 3 Cohort No.2 Cohort No. 4 (5 patients) patients) (3 patients) 70 70 m
Slide 26: Receptor Occupancy of SC Starting Dose Compared to IV Dose
RECEPTOR OCCUPANCY OF SC STARTING DOSE COMPARED TO AN IV DOSE BI-1206 serum concentration (ng/mL) Receptor occupancy (%) Time after induction therapy start (days) Time after induction therapy start (days) IV SC Solid line represents typical individual profile Shadowed region represents prediction in
Slide 27: BI-1206-02 Trial: IV & SC Overall Design
BI-1206-02 TRIAL: IV & SC OVERALL DESIGN 100mg dose selected IV Arm SC Arm 27 │
Slide 28: BI-1206-02 Trial: SC Dose Escalation Adaptive Design BLRM
BI-1206-02 TRIAL: SC DOSE ESCALATION ADAPTIVE DESIGN BLRM Starting dose 28 │
Slide 29: BI-1206-02 Trial: Impressive Early Efficacy Data
BI-1206-02 TRIAL: IMPRESSIVE EARLY EFFICACY DATA Responses From Seven Patients Completing Induction Cycle 4 4 partial responses, 1 of them ongoing SC formulation approved by all regulatory PARTIAL authorities in EU and US RESPONSES – Adaptive design, with 1 patient cohort dose-escalation design 3 3
Slide 30: How is BI-1206 Positioned in the Competitive Landscape?
How is BI-1206 Positioned in the Competitive Landscape? First approval in FL of monetuzumab Bispecific Mabs (CD3 retargeting) (CD20/CD3); class has some safety and • Many drugs in development but few tolerability issues distinct MoA Approved drugs (Gazyva) have low Fc-engineered market uptake and do
Slide 31: Rituximab Based Regimens - MCL
RITUXIMAB BASED REGIMENS - MCL Diagnosis Mantle Cell Lymphoma Treatment Stage I- Contiguous Stage II Bulky Stage II- Stage III – Stage IV • Rituximab based chemoimmunotherapies like BR, R-CHOP, R2-CHOP, R-hyper-CVAD are preferred in the frontline setting. Observation • Frontline response rates are h
Slide 32: Rituximab Will Remain a Mainstay of Therapy for Many Years
Rituximab Will Remain a Mainstay of Therapy for Many Years • Decline of Roche’s sales of Rituxan $7 billion masks a significant expected growth of the overall rituximab market, driven by: Rituximab market dynamics are favorable for the market potential – Availability of biosimilar rituximab (8 appro
Slide 33: BI-1206 in Non-Hodgkin's Lymphoma: Unique Value Proposition
BI-1206 in Non-Hodgkin’s Lymphoma: Unique Value Proposition Compelling scientific rationale in anti-CD20 refractory B-cell lymphoma First-in-class in hematology with no direct competitors High unmet need for safer -chemo-free- options in 2nd and 3rd lines Can be combined with anti-CD20s, including n
Slide 34: BI-1206 in Solid Cancer – Enhancing Anti-PD-1 Activity
BI-1206 IN SOLID CANCER – ENHANCING ANTI-PD-1 ACTIVITY 34 │
Slide 35: BI-1206 Unleashes Full Therapeutic Potential of Anti-PD-1 Antibodies
BI-1206 UNLEASHES FULL THERAPEUTIC POTENTIAL OF ANTI-PD-1 ANTIBODIES aPD-1 Fc-dependence FcgR-block aFcgRIIB aPD-1 35 │ Dahan et al Cancer Cell 2015; Arlauckas Sci Transl Med 2017; Mårtensson unpublished
Slide 36: BI-1206 with Pembrolizumab (Solid Tumors): Phase 1/2a Study with Merck
BI-1206 IN COMBINATION WITH PEMBROLIZUMAB (SOLID TUMORS): PHASE 1/2a STUDY WITH MERCK - KEYNOTE-A04 Ongoing phase STUDY OVERVIEW Part A Part B “If successful, the Patients potential addressable BI-1206 + pembrolizumab EARLY BI-1206 + pembrolizumab with: solid tumors (200mg) (200mg) market could be r
Slide 37: KEYNOTE-A04: BI-1206 and Pembrolizumab
KEYNOTE-A04: BI-1206 AND PEMBROLIZUMAB Study: Phase 1/2a Clinical Trial of BI-1206, a Monoclonal Antibody to CD32b (FcgRIIB), in Combination with Pembrolizumab in Subjects with Advanced Solid Tumors Previously Treated with Anti-PD-1 or Anti PD-L1 Antibodies Design: Phase 1: Dose Escalation Phase 2a:
Slide 38: KEYNOTE-A04: BI-1206 and Pembrolizumab
KEYNOTE-A04: BI-1206 AND PEMBROLIZUMAB Efficacy: • 1 PR still ongoing (uveal melanoma ) > 70 weeks; >50% reduction in lesions • One pseudo-progression: sarcoma patient; enrolled June 2021, PD in Jan 2022 but with clear clinical improvement – Disappearance of metastasis and radiological improvement.
Slide 39: BI-1607 (aFcgRIIB)
BI-1607 (aFcyRIIB) "e"B iolnvent
Slide 40: BI-1607 – A Novel FcgRIIB-Blocking Antibody
BI-1607 – A NOVEL FcgRIIB-BLOCKING ANTIBODY TO ENHANCE FcgR-DEPENDENT ANTITUMOR IMMUNITY 41 │
Slide 41: BI-1607 Enhances aHER2, aCTLA-4, and Beyond
BI-1607 ENHANCES ON aHER2, aCTLA-4, AND BEYOND aHER2 aCTLA-4 agp75 (tumor antigen) Breast B16 lung metastases model tumor Breast cellcell tumor TReg Melanoma Survival 2mg aCTLA-4 for presentation tumor cell 100 ctrl IgG 100 covered with metastasis 80 anti-CTLA-4 2 mg Percent Survival Percent of lung
Slide 42: BI-1607 CONTRAST Trial - Modified Anti-FcgRIIB
BI-1607 CONTRAST TRIAL - MODIFIED ANTI-FcgRIIB Study: Phase 1/2a Open-label Clinical Trial of BI-1607, an Fc-Engineered Monoclonal Antibody to CD32b (FcγRIIB), in Combination with Trastuzumab in Subjects with HER2-positive Advanced Solid Tumors – CONTRAST Design: Countries: - Currently enrolling pat
Slide 43: CONTRAST Trial: BI-1607 and Trastuzumab
CONTRAST TRIAL: BI-1607 AND TRASTUZUMAB 1st in class anti-FcgRIIB mAb Enhances efficacy of several other marketed antibodies (trastuzumab, ipilimumab) May allow dose-reduction of anti-CTLA4 FIM study in combination with trastuzumab currently in dose-escalation Our previous knowledge of the target al
Slide 44: BT-001 (Vectorized Treg-depleting aCTLA-4)
BT-001 (Vectorized Treg-depleting aCTLA-4)
Slide 45: BT-001 - Vectorized Treg-depleting aCTLA-4 for Cancer Immunotherapy
BT-001 - VECTORIZED TREG-DEPLETING aCTLA-4 FOR CANCER IMMUNOTHERAPY 1. Intratumoral injection of oncolytic virus encoding aCTLA-4 mAb 2. Infection, replication, aCTLA-4 mAb production and lysis of tumor cells 3. Antibody binding and saturation of tumor- associated CTLA-4 receptors receptors 1. Treg-
Slide 46: BT-001: Tumor-Restricted mAb Exposure and Treg-Depletion
BT-001: TUMOR-RESTRICTED mAb EXPOSURE AND TREG-DEPLETION 47 │ Semmrich, J Immunother Cancer, 2022
Slide 47: BT-001: Has Broad Anti-Tumor Activity
BT-001: HAS BROAD ANTI-TUMOR ACTIVITY INFLAMED NONINFLAMED Preexisting Immunity Excluded Infiltrate Immunologically Ignorant “hot” “cold” aPD-1R aPD-1R aPD-1S/R aPD-1S/R aPD-1S LL CT26 MC38 aCTLA-4R B16 aCTLA-4R aCTLA-4S EMT6 aCTLA-4S aCTLA-4S 48 │ Adapted from Semmrich, J Immunother Cancer, 2022
Slide 48: BT-001.01 Trial: Vectorized-Anti-CTLA4
BT-001.01 TRIAL: VECTORIZED-ANTI-CTLA4 Study: A Phase 1/2a study of intra-tumoral BT-001 (TG6030) administered alone and in combination with pembrolizumab in patients with cutaneous or subcutaneous lesions or easily injectable lymph nodes of metastatic/advanced solid tumors. Design: Evaluation W6, D
Slide 49: Ongoing Phase 1/2a Open-Label, Multicenter, Dose-Escalation Study
ONGOING PHASE 1/2a OPEN-LABEL, MULTICENTER, DOSE-ESCALATION STUDY PHASE 1 - PART A & B PHASE 2a SEVERAL COHORTS, DIFFERENT TUMOR TYPES UP TO 42 PATIENTS UP TO 12 PATIENTS PART A: PART B: Single agent BT-001 BT-001 intratumoral BT-001 intratumorally intratumoral administration administration in combi
Slide 50: BT-001.01 Trial: Vectorized-Anti-CTLA4
BT-001.01 TRIAL: VECTORIZED-ANTI-CTLA4 Third cohort of phase 1A (single agent, highest dose), 108 pfu currently ongoing Expression of the mAb in the tumor has been detected Viral replication in the tumor No systemic exposure to anti-CTLA4 Key upcoming milestones: End single agent cohort and FPI in c
Slide 51: BI-1808 (aTNFR2)
BI-1808 (a TNFR2) "e"B iolnvent
Slide 52: BI-1808: Ligand-Blocking FcgR-Engaging Anti-TNFR2
BI-1808: LIGAND-BLOCKING FcgR-ENGAGING ANTI-TNFR2 • 1st in class anti-TNFR2 mAb (BI-1808) • Compelling efficacy as single agent and in combination, across inflamed and “cold” tumor microenvironments • Differentiated mechanism-of-actions compared to other mAbs to TNFRs – Regresses pre-existing large
Slide 53: aTNFR2 Has Broad Antitumor Activity and Synergizes with aPD-1
aTNFR2 HAS BROAD ANTITUMOR ACTIVITY AND SYNERGIZES WITH aPD-1 Representative tumor growth experiment, CT26 INFLAMED NONINFLAMED 4000 Preexisting Immunity Excluded Infiltrate Immunologically Ignorant Tumour Volume (mm3) 3000 ctrl 2000 BI-1808 1000 surrogate -2 0 0 20 40 60 80 10 0 Day post therapy aP
Slide 54: KEYNOTE-D20: BI-1808 +/- Pembrolizumab
KEYNOTE-D20: BI-1808 +/- PEMBROLIZUMAB Study: Phase 1/2a Open-Label, Dose-Escalation, Multicenter, First-in-Human, Consecutive-Cohort, Clinical Trial of BI-1808, a Monoclonal Antibody to Tumor Necrosis Factor Receptor 2 (TNFR2), as a Single Agent and in Combination with Pembrolizumab in Subjects wit
Slide 55: KEYNOTE-D20: BI-1808 +/- Pembrolizumab
KEYNOTE-D20: BI-1808 +/- PEMBROLIZUMAB Currently enrolling. Approved in all countries: Europe, UK, and the USA Phase 1 Part A: • Cohort No. 5 New dose cohort ongoing (1000mg) Phase 1 Part B combination open (225 mg BI-1808/200mg pembrolizumab): • Cohort filled and patients are in observation period
Slide 56: Post-IND Competitive Landscape for TNFR2: BioInvent Leading
Post-IND Competitive Landscape for TNFR2: BioInvent Leading Drug Name Company Name Stage Description LBL-019 Nanjing Leads Phase I/II Agonist Biolabs (China) • Competitors are developing SIM-0235 Simcere Phase I humanized IgG1 antibody agonists or antagonists (but (China / US) Blocker/Depleter no ot
Slide 57: Thank You!
= Biolnvent
Slide 58: Expected Key Catalysts 2023
EXPECTED KEY CATALYSTS 2023 BI-1206 + ritux Preliminary results Phase 1 s.c H1 2023 BI-1206 + pembro Start of Phase 1 s.c. H1 2023 BI-1808 single agent Preliminary results Phase 1 H1 2023 BT-001 Start combination study with Keytruda H1 2023 BI-1808 + pembro Preliminary results Phase 1 H2 2023 BI-160
Slide 59: Our Success Factors
Our Success Factors BioInvent has one of the most exciting and unique cancer immunotherapy pipelines of any European biotech company TECHNOLOGY EXPERTISE INTEGRATION Our proprietary high-quality antibody Everything we do is based on our We can go fast to development because library and animal models
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