Slide 1: 2024 Research Investor Event
April 9, 2024 2024 Research Investor Event
Slide 2: Our UK Labs
“OC Our UK Labs 2 THERAPEUTICS
Slide 3: Agenda
3 Agenda ▪ Business Update ▪ Our Research Strategy ▪ Our Platform ▪ Lead Candidates ▪ Forward Looking ▪ Closing Remarks ▪ Q&A
Slide 4: Forward-Looking Statements
4 Forward - Looking Statements This presentation and any accompanying oral presentation have been prepared by ADC Therapeutics SA ("ADC Therapeutics“, “we” or “us”) for informational purposes only and not for any other purpose. Nothing contained in this presentation is, or should be construed as, a
Slide 5: Unlocking Potential Value of Robust ADC Portfolio
5 Unlocking Potential Value of Robust ADC Portfolio DLBCL: Diffuse Large B - Cell Lymphoma; FL: Follicular Lymphoma; MZL: Marginal Zone Lymphoma; NSCLC: Non Small - Cell Lung Cancer; ALL: Acute Lymphoblastic Leukemia. Short - Mid Term Mid - long Term Hematology Portfolio Solid Tumor Portfolio ZYNLON
Slide 6: ADC Therapeutics Business Update
6 ADC Therapeutics Business Update ▪ ZYNLONTA revenues in the first quarter of 2024 are expected to grow mid - single digit percentage sequentially vs. Q4 2023 ▪ Continued growth in the academic and community settings Commercial Performance Pipeline Progress ▪ LOTIS - 7 cleared dose escalation with
Slide 7: Agenda
7 Agenda ▪ Business Update ▪ Our Research Strategy ▪ Our Platform ▪ Lead Candidates ▪ Forward Looking ▪ Closing Remarks ▪ Q&A
Slide 8: ADC Therapeutics: A Pioneer and Leader in the ADC Field
8 ADC Therapeutics: A Pioneer and Leader in the ADC Field Experienced Team ADC Pioneer Robust Pipeline Commercial - stage pioneer in the field of ADCs, with specialized end - to - end capabilities Seeking expansion of FDA - approved ZYNLONTA®, 2 novel compounds in clinical development, and multiple
Slide 9: A Focused Research Strategy
9 A Focused Research Strategy Areas of High Unmet Patient Need Targets Amenable to an ADC Approach Tumors with high incidence, high unmet need, and high chemo use Targets that are specific, highly expressed, and effectively internalized Optimized ADC Design Platform designed with validated toxin, li
Slide 10: Focus on Areas of High Unmet Patient Need
10 Focus on Areas of High Unmet Patient Need ADT: Androgen Deprivation Therapy; HT: Hormone Therapy; 1. Applicable to metastatic castration - sensitive prostate cancer; 2. C ombined with HT or ADT; 3. Applicable to adenocarcinoma and squamous cell carcinoma; 4. Doublet/triplet regimes include FOLFOX
Slide 11: Identify Targets Amenable to an ADC Approach
11 Identify Targets Amenable to an ADC Approach Internalization Properties Tissue Specificity Membrane Expression A membrane bound antigen that can be recognized by circulating ADCs Expressed exclusively or predominantly on tumor cells, but rare or low on normal tissues Internalized upon binding of
Slide 12: Optimize ADC Design
12 Optimize ADC Design 1. Based on preclinical data in cynomolgus monkey. Peptide Spacer Adaptor Linker Toxin(s) TOXIN Near term focus on exatecan toxin in lead candidates: x Clinically validated toxin with known toxicity profile x Superior therapeutic index supports strategy to dose ADC > 5 mg/kg i
Slide 13: Executing Our Research Strategy
13 Executing Our Research Strategy NaPi2b Claudin - 6 PSMA ASCT2 NSCLC OVARIAN PAYLOAD RELEASING EXATECAN PROSTATE ENDOMETRIAL CRC Areas of High Unmet Patient Need Optimized ADC Design Targets Amenable to an ADC Approach
Slide 14: Developing Differentiated ADCs with a High Therapeutic Index
14 Amino acid transporter Enzymatic glycoprotein Adhesion protein Phosphate transporter Target description NSCLC Colorectal cancer Heme Malignancies Prostate cancer NSCLC Ovarian cancer Endometrial cancer NSCLC Ovarian cancer Endometrial cancer Tumor types of interest Exatecan Exatecan Exatecan Exat
Slide 15: Potential to be Highly Differentiated
15 Potential to be Highly Differentiated 1. Includes 1 pre - registration drug for HER2, TROP2, and HER3; 2. Mersana Therapeutics’ Ph III trial (NCT05329545) for Upifitamab Rilsodotin targeting NaPi2b has been terminated due to failure to meet primary endpoints; Tubulis NAPISTAR1 - 01 trial set to s
Slide 16: Research Focused in Large Market Opportunities
16 Research Focused in Large Market Opportunities 1. Combined Market Opportunity for Ovarian and Uterine Cancer. Source: Evaluate Pharma, Market Explorer [Accessed 04/04/2024] . $0 B $5 B $10 B $15 B $20 B $25 B $30 B $35 B $31 B $14 B $7 B Global Market Opportunity, 2023 Sales $3 B PROSTATE GYNECOL
Slide 17: Proven Capabilities for Path Forward
17 Proven Capabilities for Path Forward ADME: Absorb, Distribution, Metabolism, Excretion.1. Prior INDs have taken between 13 and 24 months. ▪ Dose Schedule / optimization ▪ Safety ▪ Early signs of activity ▪ Proof of concept in selected indications ▪ Patient selection assay / biomarker validation w
Slide 18: Agenda
18 Agenda ▪ Business Update ▪ Our Research Strategy ▪ Our Platform ▪ Lead Candidates ▪ Forward Looking ▪ Closing Remarks ▪ Q&A
Slide 19: Aspiring to Develop a Differentiated ADC Platform
19 Peptide Spacer Adaptor Linker Fc region [Engineered ] hinge region Toxin(s) ADC THERAPEUTICS PLATFORM OPTIONALITY 3 3 5 4 2 1 DAR 2 / 4 / 6 / 8: [ engineered] hinge region Drug to Antibody Ratio 3 DAR 2 / 4: Fc region Fc receptor silencing Yes 5 No Cleavable Reducible Linker 2 Non - cleavable Ami
Slide 20: Validation of Topoisomerase I Inhibitors in Oncology
20 Validation of Topoisomerase I Inhibitors in Oncology 1. This indication is approved under accelerated approval. Continued approval for this indication may be contingent upon veri fic ation and description of clinical benefit in a confirmatory trial. Source: Schoffski , Oncol Res Treat, 2024. 1990
Slide 21: A Novel Exatecan-based ADC Platform
21 A Novel Exatecan - based ADC Platform Val - Ala - PABC Exatecan = PL2202 ▪ Superior therapeutic index vs. DXd and other approved Topo1 inhibitors 1 — Preclinical data in cynomolgus monkey supports strategy to dose ADC > 5 mg/kg in patients — Enables combinability with standard of care ▪ No signs
Slide 22: Agenda
22 Agenda ▪ Business Update ▪ Our Research Strategy ▪ Our Platform ▪ Lead Candidates — NaPi2b — Claudin - 6 — PSMA — ASCT2
Slide 23: NaPi2b: A Validated ADC Target
23 NaPi2b: A Validated ADC Target Source: Wagner et al., Pflugers Arch (2014); Yin et al., Cancer Immun (2008); Banerjee et al., Cancer Treat Rev (2023); Gryshkova et al., Exp Oncol (2009) Hong et al., PLOS One (2013); Vlasenkova et al., Biomolecules (2021) ; Nurgalieva et al., Biochem Biophys (2021
Slide 24: NaPi2b: High Potential Impact in Areas of Unmet Need
24 1. Based on data from MIRASOL trial; 2. Data from platinum - based chemotherapy in EGFR+ post TKI (tyrosine kinase inhibitor) patients shown as an example. Source: Seer 2023; Colombo et al., Ann of Oncol (2019); Atallah et al., Int J Mol Sci (2023); Bax et al., Br J Cancer (2023); Davies et al.,
Slide 25: A Differentiated NaPi2b-ADC
25 NaPi2b - PL2202 Active (preclinical) Status NaPi2b - specific humanized mAb Antibody x Efficiently internalized x Fc - silenced; mitigates target - independent toxicity Exatecan Payload x Clinically validated in tumors that are sensitive to Topo - 1 inhibitors (e.g., NSCLC) Proprietary hydrophili
Slide 26: Our Potential Advantage: Superior Cell Binding and Cytotoxicity
26 Our Potential Advantage: Superior Cell Binding and Cytotoxicity Source: ADC Therapeutics Internal Studies. IC 50 pM ADCs 107.3 NaPi2b - PL2202 2473 Lifastuzumab - PL2202 27168 B12 - VA - PL2202 x NaPi2b Ab has higher binding to OVCAR - 3 cells compared to lifastuzumab EC50 pM Antibodies 398.7 NaP
Slide 27: Our Potential Advantage: Stronger Bystander Activity
27 Our Potential Advantage: Stronger Bystander Activity Source: ADC Therapeutics Internal Studies. x NaPi2b - PL2202 shows stronger bystander activity compared to NaPi2b - DXd or Lifa - vedotin ▪ Direct = NaPi2b ( - ) KB cells directly incubated with ADCs ▪ Bystander = Conditioned medium from NaPi2b
Slide 28: Strong in vivo Anti-tumor Activity with a Single Dose
28 Strong in vivo Anti - tumor Activity with a Single Dose H441 Lung - papillary Adenocarcinoma Xenograft Model Source: ADC Therapeutics Internal Studies. OVCAR - 3 Ovarian Xenograft Model TFS CR PR ADCs 0/10 0/10 9/10 NaPi2b - PL2202, 6.6mg/kg 0/10 0/10 0/10 B12 - VA - PL2202 10 mg/kg
Slide 29: Stable and Well-Tolerated in Rats and Cynomolgus Monkeys
29 ▪ PK following a single IV dose of NaPi2b - PL2202 to rats (n=3/group) ▪ Linear TK with a t½ of 12.9 - 15 days ▪ Free exatecan detectable with apparent t½ of 9.5 days ▪ Tolerated up to 300 mg/kg IV with minimal clinical pathology and histopathology findings in male rats Stable and Well - Tolerate
Slide 30: Reasons to Believe
30 Reasons to Believe TI: Therapeutic Index; IHC: Immunohistochemistry; ADME: Absorb, Distribution, Metabolism, Excretion. Source: ADC Therapeutics In ternal Studies. Validated Target With High Potential Impact x Membrane - bound antigen x Efficiently internalized x Expressed highly and specifically
Slide 31: Claudin-6: A Validated ADC Target
31 Source: Kojima et al., Cancer (2020); Fierce Biotech; STAT news; Du et al., Mol Med Rep (2021); Cao et al., Onco Targets Ther (2018); ADC Therapeutics Internal Studies. Claudin - 6 Overview: A transmembrane protein; part of the Claudin protein family ▪ Involved with creating tight junctions, regu
Slide 32: Claudin-6: High Potential Impact in Areas of Unmet Need
32 1. Based on data from MIRASOL trial; 2. Data from platinum - based chemotherapy in EGFR+ post TKI (tyrosine kinase inhibitor) patients shown as an example. Source: Seer (2023); Colombo et al., Ann of Oncol (2019); Atallah et al., Int J Mol Sci (2023); Bax et al., Br J Cancer (2023); Davies et al.
Slide 33: A Differentiated Claudin-6-ADC
33 GB01 - VA - PL2202 Asset name Active (preclinical) Status Humanized Claudin - 6 mAb Antibody x Efficiently internalized x Fc - silenced; mitigates target - independent toxicity Exatecan Payload x Clinically validated in tumors that are sensitive to Topo - 1 inhibitors (e.g., NSCLC) Proprietary hy
Slide 34: Our Advantage: Superior Cell Binding and Cytotoxicity
34 Our Advantage: Superior Cell Binding and Cytotoxicity Source: ADC Therapeutics Internal Studies. 10 -2 10 0 10 2 10 4 10 6 0 20 40 60 80 100 120 Concentration (pM) % C e l l V i a b i l i t y AB3-7-VA-PL2202GB01-VA-PL2202 B12-VA-PL2202 IC50 pM ADCs 63.67 GB01 - VA - PL2202 359.9 AB3 - 7 - VA - PL
Slide 35: Strong Bystander Activity
35 Strong Bystander Activity Source: ADC Therapeutics Internal Studies. Primary Cytotoxicity Bystander Cytotoxicity -2 0 2 4 6 0 50 100 150 PA-1 (Claudin6+) Concentration (pM) % S u r v i v a l GB01-VA-PL2202 B12-VA-PL2202 -2 0 2 4 6 0 50 100 150 KB (Claudin6-) Concentration (pM) % S u r v i v a l G
Slide 36: Strong in vivo Anti-tumor Activity with a Single Dose
36 Strong in vivo Anti - tumor Activity with a Single Dose Source: ADC Therapeutics Internal Studies. 0 10 20 30 40 0 1000 2000 3000 Time (Days) T u m o r V o l u m e ( m m 3 ) m e a n ± S E M Vehicle GB01-VA-PL2202, 3 mg/kg, qdx1 GB01-VA-PL2202, 6 mg/kg, qdx1 GB01-VA-PL2202, 9 mg/kg, qdx1 B12-VA-PL
Slide 37: Stable and Well-tolerated in Cynomolgus Monkeys
37 Stable and Well - tolerated in Cynomolgus Monkeys DLT: Dose limiting toxicity; GI: Gastrointestinal. Source: ADC Therapeutics Internal Studies. ▪ Well - tolerated up to 40 mg/kg IV with minimal clinical pathology and no histopathology findings ▪ At 60 mg/kg, the DLT was degeneration/regeneration
Slide 38: Reasons to Believe
38 Reasons to Believe TI: Therapeutic Index; IHC: Immunohistochemistry; ADME: Absorb, Distribution, Metabolism, Excretion. Source: ADC Therapeutics In ternal Studies. Path Forward Validated Target With High Potential Impact x Membrane - bound antigen x Efficiently internalized x Expressed highly and
Slide 39: PSMA: A Validated ADC Target
39 PSMA: A Validated ADC Target Source: Calais and Czernin , J Nucl Med (2021); O’Driscoll et al., Br J Pharmocol (2016); Kinoshita et al., World J Surg (2006); Sheehan et al ., Eur Urol Focus (2021); Caromile et al., Sci Signal (2017). PSMA Overview: Prostate - specific membrane antigen (PSMA) is a
Slide 40: PSMA: High Potential Impact in Areas of Unmet Need
40 PSMA: High Potential Impact in Areas of Unmet Need 1. Prior androgen receptor pathway inhibitor (ARPI) therapy; 2. Potential near future update to mCRPC treatment paradigm ( PSMAfore trial is ongoing); 3. Represents PSA response rate; 4. Standard of care (SoC) excludes chemotherapy, immunotherapy
Slide 41: PSMA-PL2202 Differentiated ADC
41 DAR: drug - antibody - ratio; RNT: Radionuclide therapy 1. Contributing factors of resistance to PSMA - based RNT include heterogenei ty of tumor PSMA expression, failure to deliver a lethal dose of radiation to metastatic sites, tumor microenvironment, and tumor biological radioresistance . Sour
Slide 42: Strong in vivo Anti-tumor Activity with Single Dose
42 Strong in vivo Anti - tumor Activity with Single Dose 1 Dosing at 1 mg/kg qdx1; ADCs with PBD warhead Source: ADC Therapeutics Internal Studies AUC (µg - days/ml) Half - life (days) 807 ± 192 15.2 ± 0.9 ADCT mAb 1 566 ± 125 6.3 ± 0.8 Ambrx mAb (J591) 1 x ADCT’s PSMA mAb has a significantly improv
Slide 43: Reasons to Believe
43 Reasons to Believe TI: Therapeutic Index; ADME: Absorb, Distribution, Metabolism, Excretion. Source: ADC Therapeutics Internal Studies. Validated Target With High Potential Impact x Membrane - bound antigen x Efficiently internalized x Expressed highly and specifically in Prostate Cancer x Clinic
Slide 44: ASCT2: A Promising Novel ADC Target
44 ASCT2: A Promising Novel ADC Target Source: ADC Therapeutics Internal Studies. ASCT2 ASCT2 is ubiquitously expressed in lung, skeletal, large intestine, kidney, testis, T - cells, brain and adipose tissue Overview: A Na+ - dependent aa exchanger (antiporter), localized at the plasma membrane and
Slide 45: ASCT2: High Potential Impact in Areas of Unmet Need
45 ASCT2: High Potential Impact in Areas of Unmet Need 1. Potential near future update to CRC treatment paradigm ( CodeBreaK 300 trial is ongoing); 2. Chemotherapy regimes include combinations or 5 - fluorouracil (5FU)/leucovorin or capecitabine with oxa liplatin or irinotecan, or irinotecan alone,
Slide 46: Potential First-in-Class ASCT2-ADC
46 Potential First - in - Class ASCT2 - ADC DAR: drug antibody ratio ; 1. Calculated from Maximum Tolerated Dose (MTD) in cynomolgus monkey / Minimum Effective Dose (MED) in mouse. ASCT2 - PL2202 Asset name Active (preclinical) Status ASCT2 - specific mAb Antibody x Fc - silenced mitigates target -
Slide 47: Strong Cell Surface Binding in Heme and Solid Tumors
47 Strong Cell Surface Binding in Heme and Solid Tumors Source: ADC Therapeutics Internal Studies In vitro Cell Surface Binding -4 -2 0 2 4 6 0 100000 200000 300000 400000 500000 1180B2 Log 10 (ng/ml) M F I ( M e d i a n F I T C - A ) OVCAR-3 G-402 Raji MOLM-13 HT Copy number ± SEM Cell line 329284
Slide 48: Strong in vivo Anti-tumor Activity: Solid Tumors
48 Strong in vivo Anti - tumor Activity with a Single Dose Solid Tumors PR: partial regression; CR = complete regression; TFS= tumor free survivor. Source: ADC Therapeutics Internal Studies. OVCAR - 3 (Ovarian Carcinoma) Xenograft Model 0 5 10 15 20 25 30 35 40 45 0 400 800 1200 1600 Days M e a n T
Slide 49: Strong in vivo Anti-tumor Activity: Hematology
49 Strong in vivo Anti - tumor Activity with a Single Dose Hematology PR: partial regression; CR = complete regression; TFS= tumor free survivor. Source: ADC Therapeutics Internal Studies. MOLM - 13 (AML) Xenograft Model Raji B (Burkitt’s lymphoma) Xenograft Model TFS CR PR Treatment 2 5 1 10 mg/kg
Slide 50: ASCT2-PL2202 is Well-Tolerated in Cynomolgus Monkey
50 60 mg/kg ASCT2 - PL2202 43 n=2 1 22 50 mg/kg 40 mg/kg ASCT2 - PL2202 43 n=3 1 22 7 n=1 ▪ Cynomolgus monkeys are pharmacologically relevant species for ASCT2 - PL2202 ▪ Well - tolerated at doses up to 40 mg/kg IV with minimal clinical pathology and no histopathology findings in male cynomolgus mon
Slide 51: Reasons to Believe
51 Reasons to Believe TI: Therapeutic Index; IHC: Immunohistochemistry; ADME: Absorb, Distribution, Metabolism, Excretion. Source: ADC Therapeutics In ternal Studies. Promising Target With High Potential Impact x Membrane - bound antigen x Efficiently internalized x Expressed highly in NSCLC, CRC, a
Slide 52: Agenda
52 Agenda ▪ Business Update ▪ Our Research Strategy ▪ Our Platform ▪ Lead Candidates ▪ Forward Looking ▪ Closing Remarks ▪ Q&A
Slide 53: A Diverse Spectrum of Payloads
53 A Diverse Spectrum of Payloads Camptothecin derivatives Class description Commercial / clinical payload examples Reported benefits DNA - damaging agents Immunomodulators PBD DNA crosslinker Activates immune system DNA cleavage and damage Disrupts DNA synthesis PBD TLR 7 agonist Duocarmycin Exatec
Slide 54: The Future of Our Payloads
54 The Future of Our Payloads Source: ADC Therapeutics Internal Studies. Exatecan Platform PA1 Ovarian teratocarcinoma xenograft TLR7 Platform Vehicle Target1, 2.5 mg/kg Target1 - TLR7, 2.5 mg/kg 50 HCC1954 Breast cancer xenograft Duocarmycin Platform PA1 Ovarian teratocarcinoma xenograft Target1 -
Slide 55: The Forefront of Next-Generation ADC Development
55 The Forefront of Next - Generation ADC Development Branched Stable Linkers Dual Conjugation Sites More than one toxin per payload Toxin 1 Toxin 1 Alternative Toxins & Conjugation Sites Toxin 2 Toxin 2 Toxin 1 Toxin 1 Two drugs with orthogonal MOA MOA: Mode of Action Source: ADC Therapeutics Inter
Slide 56: Agenda
56 Agenda ▪ Business Update ▪ Our Research Strategy ▪ Our Platform ▪ Lead Candidates ▪ Forward Looking ▪ Closing Remarks ▪ Q&A
Slide 57: Business Development to Unlock Value
57 HEMATOLOGY ZYNLONTA, ADCT - 602 SOLID TUMORS ADCT - 601, Research Assets Business Development to Unlock Value Business Development Goals: U.S. EX - U.S. Co - development & Co - promote* Royalty & Milestones to ADCT Accelerate & Expand Asset Development 3 Non - dilutive Financing 2 Maximize Deal V
Slide 58: Closing Summary
58 Closing Summary ▪ Pioneer in the ADC space with an approved product and multiple clinical assets ▪ At the forefront of next - generation ADC development with a proven track record of selecting the optimal targeting moiety, linker, and payload to establish a therapeutic window ▪ Lead preclinical c
Slide 59: Q&A
Q&A
Slide 60: Appendix
Appendix THERAPEUTICS Wvating Science. Inspiring Hope.
Slide 61: Future of ADCs
61 Future of ADCs 3 rd gen 1 st gen Bispecifics / Biparatopic Abs Humanized/fully human Abs (non - immunogenic) Murine Abs (immunogenic) Antibody Branched stable linkers Stable (precise tumor release) Unstable (non - specific release) Linker Single conjugation sites or dual conjugation sites Site -
Slide 62: Key Patent Portfolio
62 Each of the Exatecan programs has a composition of matter filing for the antibody drug conjugate per se with long expiry dates In - licensed composition of matter patent protection (exclusive) for Claudin - 6 antibody US, EU, CN, JP – base expiry 05/2041 with possible extensions up to 05/2046 204
Slide 63: Regulatory Exclusivities
63 Regulatory Exclusivities REGULATORY DATA PROTECTION ▪ 12 years from approval with a possible pediatric extension of 6 months ▪ 10 years from approval ▪ 8 - year re - examination period with a possible 2 - year pediatric extension
Slide 64: Conjugation Strategy Optionality
64 CORPORATE Conjugation Strategy Optionality Note: 1 All methods are compatible with wide range of linkers and allow for site - specific conjugation, adjustable DAR, and combination payload options; 2 GlycoConnect licensed from Synaffix ; 3 SPAAC: strain - promoted azide - alkyne cycloaddition; 4 M
Slide 65: A Diverse Toolbox of Linkers
65 A Diverse Toolbox of Linkers Source: Alas et al., J Med Chem (2022); Lu et al., Int J Mol Sci (2016); Sheyi et al., Pharmaceutics (2022); Su et al., Acta Pharm Sin B (2021); Dal Corso et al., Bioconjug Chem (2017) Non - cleavable linkers Cleavable linkers – Glucuronidase Protease / peptidase Glut