Assembly Biosciences, Inc. · NASDAQ:ASMB
Assembly Biosciences — Technical Presentation (August 2022)
43 slides from Assembly Biosciences's technical presentation, Aug 31, 2022
Slide 1: Building Beyond Hepatitis B/D: HSV-2 & Transplant-Associated Herpesviruses
Building Beyond Hepatitis B/D: HSV-2 & Transplant-Associated Herpesviruses Aug 31, 2022 Nasdaq: ASMB ©2020 ASSEMBLY BIOSCIENCES, INC. 1
Slide 2: Agenda
Agenda • Applying unparalleled expertise in virologic drug development to expand Assembly Bio’s portfolio into new viral diseases – John McHutchison AO, MD, Chief Executive Officer at Assembly Bio • Assembly Bio’s differentiated antiviral approach for HSV-2 and an early look at the program for trans
Slide 3: Today's Speakers
Today’s Speakers John McHutchison AO, MD William Delaney, PhD Sir Michael Houghton, PhD Chief Executive Officer Chief Scientific Officer Director, Li Ka Shing Applied Virology Institute, University of Alberta, Edmonton, Canada 3
Slide 4: Cautionary Note Regarding Forward-Looking Statements
Cautionary Note Regarding Forward-Looking Statements The information in this presentation contains forward-looking statements that are subject to certain risks and uncertainties that could cause actual results to materially differ. These risks and uncertainties include: Assembly Bio’s ability to suc
Slide 5: Advancing a Clinical & Research Stage Portfolio of Small Molecules for HBV and Other Viral Diseases
Advancing a Clinical & Research Stage Portfolio of Small Molecules for HBV and Other Viral Diseases RESEARCH DEVELOPMENT Lead IND China Worldwide Drug Candidate Optimization Phase 1 Phase 2 Phase 3 Identification Enabling Rights Rights Next Gen CI† 3733 HBV* 4334 HBV/HDV HBV/HDV Entry Inhibitor Inte
Slide 6: Expansion of Assembly Bio's Discovery & Development Efforts into New Viral Areas
Expansion of Assembly Bio’s Discovery & Development Efforts into New Viral Areas High-recurrence Chronic Hepatitis B Genital Herpes (HBV) (HSV-2) 296 Million Patients1 Up to 13 Million Patients3 Transplant-associated Chronic Hepatitis Delta Herpesviruses (HDV) (CMV, HSV-1, HSV-2, VZV) 12 Million Pat
Slide 7: Agenda
Agenda • Applying unparalleled expertise in virologic drug development to expand Assembly Bio’s portfolio into new viral diseases – John McHutchison AO, MD, Chief Executive Officer at Assembly Bio • Assembly Bio’s differentiated antiviral approach for HSV-2 and an early look at the program for trans
Slide 8: Selection of New Antiviral Opportunities for Assembly Biosciences
Selection of New Antiviral Opportunities for Assembly Biosciences Liver Chronic Transplant Acute/Respiratory Broad evaluation of >20 viruses 4 high unmet needs aligned with Assembly’s strengths Exploratory Research Transplant- High-recurrence associated Genital Herpes Herpesviruses (HSV-2) (CMV, HSV
Slide 9: Expansion to New Viral Opportunities
Expansion to New Viral Opportunities High-recurrence Genital Herpes Transplant-associated Herpesviruses HSV-2 CMV HSV-1 HSV-2 VZV Up to 13 Million Patients1 60,000 Patients2 • painful recurrent lesions >6x per year • uncontrolled viral replication and severe • transmission risk (including neonatal)
Slide 10: Herpesviruses: A Virus Family Including Several Highly Prevalent Viruses
Herpesviruses: A Virus Family Including Several Highly Prevalent Viruses that Cause Human Disease Oral herpes Gamma Herpes Simplex Virus 1 Primary genital herpes (HSV-1) Keratitis herpesviruses Encephalitis Alpha HHV-8 herpesviruses Primary genital herpes EBV Herpes Simplex Virus 2 HSV-1 Recurrent g
Slide 11: High-recurrence Genital Herpes
High-recurrence Genital Herpes 11
Slide 12: HSV-2 Epidemiology and Disease Burden
HSV-2 Epidemiology and Disease Burden • HSV is a lifelong disease and causes painful lesions High- in the oral (HSV-1) and genital areas (HSV-2) recurrence Up to 13 HSV-2 • Many HSV patients suffer frequent recurrence million1 of lesions (≥6/year) which can be painful, severe and cause psychological
Slide 13: Herpes Simplex Virus
Herpes Simplex Virus Latency Envelope Nucleocapsid HSV capsid Glycoproteins retrograde transport Tegument dsDNA Stress/ trigger • Large enveloped DNA virus Reactivation • Infects epithelial cells HSV anterograde transport • Maintains latency in neurons • Reactivates during stress • Infection is life
Slide 14: Majority of Patients with High HSV-2 Recurrence Still Experience Recurrence on Daily SOC
Majority of Patients with High HSV-2 Recurrence Still Experience Recurrence on Daily SOC Treatment Suppressive regimens for patients with Patients with prior history of high HSV-2 recurrence 100 >6 recurrences/year* 80 Recurrence free (%) 60 40 34 34 Acyclovir Valacyclovir Famciclovir 400 mg 1000 mg
Slide 15: Improving Antiviral Exposure Reduces HSV-2 Recurrence
Improving Antiviral Exposure Reduces HSV-2 Recurrence Valacyclovir 60 Recurrence free after 1 year 50 Recurrence Free (%) 1000 mg 40 500 mg 30 20 250 mg 10 0 0 5 10 15 20 Acyclovir (h*ug/mL) Reitano, et al. J. Infect. Dis. 1998 15
Slide 16: Chronic HSV-2 Infection – Current Unmet Need
Chronic HSV-2 Infection – Current Unmet Need HSV-2 causes genital herpes and frequent disease recurrence in up to 13 million patients1 Lowering viral load reduces recurrence frequency, viral shedding, and transmission rates Current chronic treatment options require a high daily dose, often multiple
Slide 17: Assembly Bio's Approach: Long-Acting Injectable Antiviral Therapy
Assembly Bio’s Approach: Long-Acting Injectable Antiviral Therapy Once daily oral Long-acting injectable (90 pills) (1 injection) Plasma Concentration Plasma Concentration Efficacious Efficacious Cmin Cmin 3 months 3 months 17
Slide 18: Long-acting Injectable Therapies: Rationale and Recent Advances
Long-acting Injectable Therapies: Rationale and Recent Advances Benefits of Long Acting Therapies 3 Approved HIV Long-acting Therapies – Ability to optimize dose, plasma concentrations greater efficacy – Improved adherence Lenacapavir – Eliminates mental burden, daily reminder of disease Cabotegra
Slide 19: The HSV Helicase/Primase is a Clinically Validated Target
The HSV Helicase/Primase is a Clinically Validated Target • Helicase/primase is an essential viral enzyme • Pritelivir (phase 3 helicase/primase inhibitor) HSV demonstrated significantly improved clinical efficacy Helicase-Primase compared to valacyclovir1 Complex UL5 − greater reductions in HSV she
Slide 20: HSV-2 Long-Acting Inhibitor Target Product Profile (TPP)
HSV-2 Long-Acting Inhibitor Target Product Profile (TPP) Virologic Profile PK Profile Safety Profile • Potent antiviral activity • Subcutaneous injection • No clinically-significant against HSV-2 and HSV-1 (4-6 per year) side effects; suitable (EC50 ≤ 5 nM) for chronic dosing • Plasma Cmin ≥ 10-fold
Slide 21: Critical Properties for a Long-Acting Injectable Therapeutic
Critical Properties for a Long-Acting Injectable Therapeutic High Potency to minimize dose that needs to be administered Low Clearance to provide long T½ and maximize exposure • Assembly Bio’s approach to incorporate ideal properties for long acting from program initiation • Historically, drugs desi
Slide 22: Identification of Potent and Low Clearance Helicase/Primase Inhibitors
Identification of Potent and Low Clearance Helicase/Primase Inhibitors Antiviral Evaluation Clearance Evaluation HSV-1 and -2 Antiviral Assays Microsome Stability Assay Vero Cells (Kidney cell line) Liver Microsomes + 4 Days 45 minutes Cell viability Compound quantification by LC-MS 22
Slide 23: Identification of Potent HSV-2 Inhibitors Suitable for Long-acting
Identification of Potent HSV-2 Inhibitors Suitable for Long-acting Cell-based Preclinical Antiviral Activity & Microsomal Stability HSV-2 Antiviral Activity Antiviral Activity Human 125 EC50 (nM) Compound Microsomal Relative to DMSO Control Series 1 Stability* % Virus Replication 100 Series 2 HSV-1
Slide 24: Novel Helicase/Primase Inhibitors Demonstrate High Potential as Long-acting Agents
Novel Helicase/Primase Inhibitors Demonstrate High Potential as Long-acting Agents via Subcutaneous Delivery 10000 Plasma Concentration (ng/mL) 1000 Non-Human Primate Canine 100 10 1 0 10 20 30 40 50 60 Time (Days) Single 10 mg/kg SC injection with Series 1 compound 24
Slide 25: HSV-2 Long-Acting Helicase Inhibitor: Progress and Goals
HSV-2 Long-Acting Helicase Inhibitor: Progress and Goals Project is progressing rapidly toward identification of development candidate • Multiple chemically-differentiated leads with ≤20 nM potency • Scaffolds with pharmacokinetic data that strongly support long-acting profile • Anticipate advancing
Slide 26: Long-Acting HSV-2 Helicase Inhibitor Project: Summary
Long-Acting HSV-2 Helicase Inhibitor Project: Summary Patients with frequent Current therapies for A long-acting therapy We have discovered HSV-2 recurrence have HSV-2 are only has potential to drive multiple novel series of a high disease burden partially efficacious and greater efficacy, HSV helic
Slide 27: Transplant-associated Herpesviruses
Transplant-associated Herpesviruses 27
Slide 28: Epidemiology and Disease Burden of Herpesviruses
Epidemiology and Disease Burden of Herpesviruses • Herpesviruses are highly prevalent Solid Organ Homologous Stem – CMV positivity is ~60% Transplant Cell Transplant 100 – HSV positivity is ~60% – VZV positivity is ~80% 75 • These viruses establish % reactivation lifelong latent infections and frequ
Slide 29: Herpesvirus Structure
Herpesvirus Structure Herpesvirus Alpha Beta Gamma Envelope Glycoproteins HSV-1 CMV EBV HSV-2 HHV-6 KSHV Tegument VZV HHV-7 Nucleocapsid • Enveloped DNA virus (~200 nm diameter, 230kb dsDNA) • Herpesviruses encode a viral polymerase which is essential for replication dsDNA • Strong homology between
Slide 30: Herpesvirus Replication Cycle and Approved Therapies
Herpesvirus Replication Cycle and Approved Therapies No Single Drug Active Against All Herpesviruses Approved for Use Compound Viral Target CMV HSV-1/-2 VZV Acyclovir Polymerase Famciclovir Polymerase Foscarnet Polymerase Viral Kinase Ganciclovir Polymerase Cidofovir Polymerase Terminase Maribavir V
Slide 31: Rationale for a Pan-Herpes Antiviral for Immunosuppressed Patients
Rationale for a Pan-Herpes Antiviral for Immunosuppressed Patients Multiple herpesviruses frequently reactivate in immunosuppressed patients and can cause severe disease Existing antivirals do not have broad activity against clinically relevant herpesviruses Existing antiviral therapies have further
Slide 32: Assembly Bio's Approach: Develop an Oral Antiviral Active against CMV, HSV-1, HSV-2, VZV
Assembly Bio’s Approach: Develop an Oral Antiviral Active against CMV, HSV-1, HSV-2, and VZV Polymerases • Viral DNA polymerase essential for replication of all herpesviruses • DNA polymerases are >87% identical in active site across clinically-relevant herpesviruses • Viral polymerase is a clinical
Slide 33: Pan-Herpes Polymerase Inhibitor Target Product Profile (TPP)
Pan-Herpes Polymerase Inhibitor Target Product Profile (TPP) Virologic Profile PK Profile Safety Profile • Potent antiviral activity • Oral dosing (≤500 mg) • No clinically-significant side (EC50 ≤10 nM) effects; suitable for long- • Plasma Cmin ≥ 10-fold term dosing (~12 months) • Activity across C
Slide 34: Establishing Antiviral Activity of Pan-Herpes Polymerase Inhibitors
Establishing Antiviral Activity of Pan-Herpes Polymerase Inhibitors Cell-based Preclinical Antiviral Assays CMV Antiviral Assay HSV-1 & HSV-2 Antiviral Assays VZV Antiviral Assay MRC-5 MRC-5 Vero Cells (Lung fibroblast (Lung fibroblast (Kidney cell line) cell line) cell line) + + + 7 Days 4 Days 3 D
Slide 35: Identification of Novel Potent Pan-Herpes Polymerase Inhibitors
Identification of Novel Potent Pan-Herpes Polymerase Inhibitors Cell-based Preclinical Antiviral Activity Series 1 Series 2 Series 3 Letermovir 125 Relative to DMSO Control % Virus Replication 100 75 50 25 0 01 01 10 0 10 0 01 10 0 1 00 1 00 1 00 0 0 0 1 1 1 01 10 0 1 00 0 1 00 00 00 0. 10 0. 10 0.
Slide 36: Pan-Herpes Polymerase Inhibitor: Progress and Goals
Pan-Herpes Polymerase Inhibitor: Progress and Goals Project is in early lead optimization • Multiple novel chemically-differentiated hits with pan-antiviral activity • Antiviral assays developed to optimize pan-herpes activity • Currently optimizing antiviral potency and DMPK properties • Anticipate
Slide 37: Pan-Herpes Polymerase Inhibitor Project: Summary
Pan-Herpes Polymerase Inhibitor Project: Summary Multiple herpesviruses can cause significant morbidity and mortality in immunocompromised patients HSV-1 Current antivirals are not broad spectrum and have tolerability and drug interaction limitations in immunosuppressed patients HSV-2 An oral pan-he
Slide 38: Agenda
Agenda • Applying unparalleled expertise in virologic drug development to expand Assembly Bio’s portfolio into new viral diseases – John McHutchison AO, MD, Chief Executive Officer at Assembly Bio • Assembly Bio’s differentiated antiviral approach for HSV-2 and an early look at the program for trans
Slide 39: Sir Michael Houghton, PhD
Sir Michael Houghton, PhD • World-renowned scientist and Nobel laureate; international leader in virology and hepatitis • In 1989, his laboratory and collaborators identified the hepatitis C virus and then developed blood tests that have prevented millions of infections around the world; Dr. Houghto
Slide 40: Q&A
O assemblybio Q&A
Slide 41: Agenda
Agenda • Applying unparalleled expertise in virologic drug development to expand Assembly Bio’s portfolio into new viral diseases – John McHutchison AO, MD, Chief Executive Officer at Assembly Bio • Assembly Bio’s differentiated antiviral approach for HSV-2 and an early look at the program for trans
Slide 42: Advancing a Clinical & Research Stage Portfolio of Small Molecules for HBV and Other Viral Diseases
Advancing a Clinical & Research Stage Portfolio of Small Molecules for HBV and Other Viral Diseases RESEARCH DEVELOPMENT Lead IND China Worldwide Drug Candidate Optimization Phase 1 Phase 2 Phase 3 Identification Enabling Rights Rights Next Gen CI† 3733 HBV* 4334 HBV/HDV HBV/HDV Entry Inhibitor Inte
Slide 43: Key Objectives and Anticipated Progress
Key Objectives and Anticipated Progress o Initiate Phase 1b Study – 3733 o Introduce HBV/HDV entry inhibitor program o Introduce orally-bioavailable small molecule interferon-α receptor (IFNAR) agonist 2022 o Introduce high-recurrence HSV-2 and transplant-associated herpesviruses programs o Initiate
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