Slide 1: MultiCell Immunotherapeutics Overview Fall 2016
MultiCell Immunotherapeutics Overview FALL 2016
Slide 2: Immuno-Oncology Therapeutics
Slide 3: Antibody-Drug Conjugates: Therapeutic Mechanism of Action
Antibody-Drug Conjugates Therapeutic Mechanism of Action @ ADC in plasma Se 32 ¥ (2) ADC binds to receptor ADC-receptor complex is internalized (5) Apoptosis (cell death) Reference: Carter PJ et al. Cancer/. 2008;14(3):154-169. ‘MuliiCell Immunotherapeuties
Slide 4: Top Companies and ADC in Pipeline
TOP 5 Companies and ADC in Pipeline MF. Hoffmann-La Roche Ltd. @PhilogenS.p.A. MSeattle Genetics, Inc. ADC Therapeutics Sarl SlmmunoGen, Inc. MultiCell Immunotherapeuties
Slide 5: FDA Approved Antibody-Drug Conjugates
FDA Approved Antibody-Drug Conjugates @so0cetris’ son Powder for concentrate for oe ia brentximab vadotin a Kadcyla™ (ado-trastuzumab emtansine) For Injection 100 mg per vial For Intravenous infusion Only Reconstitute and Dilute prior to administration Single-Dose Vial ~ = - KAA Discard Unused Porti
Slide 6: Antibody-Drug Conjugates Clinical Trials
Antibody-Drug Conjugates Clinical Trials ‘erst anton LUnker rotor compu = “umour v = staus co bake lyase Ac weer Ace mo ema ne U5 104 encase 500 Noe eSebemian "a nian sett Gahan we Sreramuman vesoun ACCT, Deri, AMMA enum feupaverscoyvoan Scab Genexs Ss DA conga ape 82011 Sooo cine phen ard tent mapa
Slide 7: ADC Partnership Valuations
ADC Partnership Valuations Partnershi Deta ns)* Date of deal of deal (US$ m Licensee (buyer) Licenser (seller) Upfront payment Milestone payments (potential) Celgene Sutro Biopharma $500 Not applicable Dec 2012 Abbott Seattle Genetics $25 $220 Oct 2012 Merck Ambrx $15 $288 Jun 2012 Eli Lilly ImmunoG
Slide 8: Immuno-Oncology Therapeutic Development Strategy
Immuno-Oncology Therapeutic Development Strategy a A new category of targeted therapeutics: > Antibody Drug Conjugates (ADC) with Dual Drug Payloads > Intra-cellular release, Extra-cellular release, or Intra/Extra cellular release of drug payloads MultiCell immunotherapeutics
Slide 9: Therapeutic Rationale
Therapeutic Rationale = Targeted co-delivery of different compounds that have distinct yet synergistic mechanisms of action > Improves on approved therapies and addresses their life-cycle management needs » Advances innovative therapies MultiCell Immunotherapeutics
Slide 10: ADCs to Effectively co-Target Cancerous Cells and Stroma
ADCs to Effectively co-Target Cancerous Anti-tubulin agents tiara) Tyrosine kinase inhibitors Sunitinib) Proteasome inhibitors (bortezomib) Cytotoxic dsRNA (MCT485)\, Cells and Stroma Linker Linker cleaved cleaved within the within the extracellular cell environment IMIDs (lenalidomide, pomalidomide
Slide 11: Dual Drug Targeting and Release Strategy
Dual Drug Targeting and Release Strategy Heterobifunctional scaffold Linker cleaved within the Linker cleaved ousidete Matrix Metalloproteinases 2 & 9 i Cathepsin B bad Cell death or innibiton of, proliferation Increase cell susceptibiily to chemotherapies .: Intracellular release: x Extracellular r
Slide 12: Platform's Components
Platform’s Components = Targeted delivery vector > Proprietary humanized antibodies o Anti-FZD7 mAb « Key component of the WNT pathway responsible for epithelial to mesenchymal transition (EMT) « Expressed on significant percentage of solid tumors including triple negative breast carcinoma and hepat
Slide 13: Platform's Components
Platform’s Components a Innovative linkers and tethers that accommodate two distinct payloads onto mAb with control of the drug antibody ratio (DAR) and relative load > Compatible with conventional payload loading chemistry » Features two categories of linkers o Cleavable by Matrix Metaloproteinases
Slide 14: Platform's Components
Platform’s Components = Payload categories > Requiring intra-cellular delivery o Cytotoxics (chemotherapies) o Cytostatic agents (small molecule targeted therapies) » Requiring extra-cellular delivery (diffusion within tumor microenvironment) Immune modulating agents Anti-angiogenic agents o Anti-me
Slide 15: MCIT-455 Taxol-Doxorubicin Dual Drug Payload ADC Linker
MCIT-455 Taxol-Doxorubicin Dual Drug Payload ADC Linker Le Ke een ow ¢ eh bed be Soe od fae am OR OT ca on OD oat al tnpesmobya ts we XVI wl? $2 4 De ‘MultiCell Immunotherapeutics 15
Slide 16: MCIT-485 siRNA ADC Linker Technology
MCIT-485 siRNA ADC Linker Technology MuttiCell Immunotherapeuties 16
Slide 17: Validated Development Platform
Validated Development Platform ma $540 Million Development & Product License Agreement Completed with Oxis Biotech > $500K Up-front License & Technology Access Fees » $1.225 Million in R&D Cost Reimbursement > $12.75 Million in Clinical Development Milestone Payments > $10 Million Option for Manufac
Slide 18: Product Pipeline
MCIT-255, MCIT-355 MCIT-375 MCIT-455 MCIT-485 Product Pipeline Description Anti-FZD7/TAXOL/IMIQUIMOD Dual Drug Payload ADC Anti-FZD7/SUNITINIB/IMIQUIMOD Dual Drug Payload ADC Anti-CD38/BORTEZOMIB/LENALIDOMIDE Dual Drug Payload ADC Anti-FZD7/TAXOL/DOXORUBICIN Dual Drug Payload ADC Anti-FZD7/siRNA. Ta
Slide 19: Breast Cancer Strategy
Breast Cancer Strategy = Development of the first immune activating taxol > Anti-FZD7 mAb as vector (target highly expressed in TNBC) > Payload 1 and linker for intra-cellular delivery of Taxol (anti-tubulin agent approved for breast cancer treatment) > Payload 2 and linker for extrcellular delivery
Slide 20: ADC for TNBC: The First Targeted and Immunologically Active Taxol
ADC for TNBC: The First Targeted and Inhibition MultiCell immunotherapeutics immunologically Active Taxol Linker Linker cleaved cleaved within the within the extracellular environment 4g IMIQUIMOD se \ \, IMIQUIMOD of proliferation \ and apoptosis \ of dividing cells \ \ pod N bes Apoptosis Cancerou
Slide 21: An ADC Strategy for Hepatocellular Carcinoma
An ADC Strategy for Hepatocellular Carcinoma = Development of the first immune activating tyrosine kinase inhibitor > Anti-FZD7 mAb as vector (target highly expressed in hepatocellular carcinoma) > Payload 1 and linker for intra-cellular delivery: Sunitinib (multi-tyrosine kinase inhibitor approved
Slide 22: ADC for HCC: The First Targeted and Immunologically Active Sunitinib
ADC for HCC: The First Targeted and Immunologically Active Sunitinib Linker Linker cleaved cleaved within the within the extracellular environment IMIQUIMOD ” 5 IMIQUIMOD Induction of \ : Robust apoptosis LR7 activation of local and systemic immunity against Immune cells — tumor antigens Activity mo
Slide 23: ADC for Hepatocellular Carcinoma (HCC)
ADC for Hepatocellular Carcinoma (HCC) = Sunitinib is the basis for standard of care of unresectable HCC ($B+ worldwide sales) = Imiquimod is a potent immune activator, a niche drug for skin cancer = FZD7 is prevalent in HCC which continues to be a major unmet medical need = An anti-FZD7 ADDC integr
Slide 24: An ADC Strategy for Multiple Myeloma
An ADC Strategy for Multiple Myeloma = Development of the first targeted and immune activating proteasome inhibitor > Anti-CD38 or Anti-ICAM mAb as vector (target highly expressed in multiple myeloma) > Payload 1 and linker for intra-cellular delivery of bortezomib (proteasome inhibitor approved for
Slide 25: ADC for Multiple Myeloma: Integrating Two Key Mechanisms
ADC for Multiple Myeloma: Integrating Two Key Mechanisms within a Single Targeted Compound Linker Linker cleaved cleaved within the within the extracellular environment 4, LENALIDOMIDE cell i 4 BOI EZOMIB , \ LENALIDOMIDE Induction of ‘ \ apoptosis \ \ \ \ \. \ # bes Apoptosis Cancerous cell express
Slide 26: ADC for Multiple Myeloma
ADC for Multiple Myeloma = Proteasome inhibitors and IMIDs are major components of the standard of care in myeloma ($B+ worldwide sales) = CD38 expression is prevalent and a validated target in Multiple Myeloma = Myeloma continues to be a major unmet medical need as it is not curable = An anti-CD38
Slide 27: Anti-FZD7 Taxol-Imiquimod ADC Development Timeline
Anti-FZD7 Taxol- Imiquimod ADC Development Timeline Jan Feb Mar Apr May Jun Jul Aug Sep Oct Nov Select chemistry vendors Generate tether, linker, Taxol Test these components If components non-toxic Secure clone from Abnova Select CRO ‘Humanize anti-FZD7 antibody Demonstrate equivalence Ls, of humani
Slide 28: Summary
Summary = Targeted therapy = Within the rapidly growing immuno-oncology space u Leverages advanced protein-drug conjugate engineering = Tackles complexity of tumor biology = Dual opportunity: platform technology and specific therapeutic candidates ‘MultiCell Immunotherapeutics a
Slide 29: MultiCell Immunotherapeutics Overview
MultiCell Immunotherapeutics Overview FALL 2016