Slides
Page 1
NON CONFIDENTIAL 1 Sutro Biopharma 43rd Annual J.P. Morgan Healthcare Conference January 2025 Sutro Biopharma NASDAQ: STRO
Page 2
NON CONFIDENTIAL 2 Forward-Looking Statements This presentation and the accompanying oral presentation contain “forward-looking” statements that are based on our management’s beliefs and assumptions and on information currently available to management. Forward-looking statements include all statements other than statements of historical fact contained in this presentation, including information concerning our future financial performance; business plans and objectives; anticipated preclinical and clinical development activities, including enrollment and site activation; timing of announcements of clinical results, trial initiation, and regulatory filings; outcome of regulatory decisions; our expectations about our cash runway; potential benefits of luvelta and our other product candidates and platform; potential expansion into other indications and combinations, including the timing and development activities related to such expansion; potential growth opportunities, financing plans, potential future milestone and royalty payments, competitive position, industry environment and potential market opportunities for our product candidates. Forward-looking statements are subject to known and unknown risks, uncertainties, assumptions and other factors, including risksand uncertainties related to our cash forecasts, our and our collaborators’ ability to advance our product candidates, the receipt, feedback and timing of potential regulatory submissions, designations, approvals and commercialization of product candidates and the design, timing and results of preclinical and clinical trials and our ability to fund development activities and achieve development goals. It is not possible for our management to predict all risks, nor can weassess the impact of all factors on our business or the extent to which any factor, or combination of factors, may cause actual results to differ materially from those contained in any forward- looking statements we may make. These factors, together with those that may be described in greater detail under the heading“Risk Factors” contained in our most recent Annual Report on Form 10-K, Quarterly Report on Form 10-Q and other reports the company files from time to time with the Securities and Exchange Commission, may cause our actual results, performance or achievements to differ materially and adversely from those anticipated or implied by our forward-looking statements. You should not rely upon forward-looking statements as predictions of future events. Although our management believes that the expectations reflected in our forward-looking statements are reasonable, we cannot guarantee that the future results, levels of activity, performance or events and circumstances described in the forward-looking statements will be achieved or occur. Moreover, neither we nor our management assume responsibility for the accuracy and completeness of the forward-looking statements. We undertake no obligation to publicly update any forward-looking statements for any reason after the date of this presentation to conform these statements to actual results or to changes in our expectations, except as required by law. This presentation also contains estimates and other statistical data made by independent parties and by us relating to market size and growth and other data about our industry. This data involves a number of assumptions and limitations, and you are cautioned not to give undue weight to such estimates. In addition, projections, assumptions, and estimates of our future performance and the future performance of the markets in which we operate are necessarily subject to a high degree of uncertainty and risk. 2
Page 3
NON CONFIDENTIAL 3 Advancing Next-Generation ADCs with Proprietary Cell-free XpressCF® Discovery Platform 3 Proprietary Cell-free XpressCF® Platform Drives Significant Discovery and Manufacturing Opportunities for Sutro and its Partners Luvelta: potential best-in-class tubulin inhibitor ADC for a range of FRα expressing cancers • T wo registrational trials ongoing and multiple follow-on opportunities Pipeline Partnerships & Collaborations STRO-004 and Next-Generation ADCs: T argeting three INDs over the next three years • STRO-004: a potential best-in-class exatecan ADC targeting tissue factor with broad, pan-tumor potential (IND expected 2H 2025) • Novel ADCs are engineered with unique features that are not achievable with other platforms to enhance functionality inside and outside the tumor Partnerships across multiple modalities validating platform and generating significant capital ~$975 million in funding*, with over $2 billion in potential future milestones plus royalties *Includes payments and equity investments received through September 30,2024.
Page 4
NON CONFIDENTIAL 4 Three-pronged R&D strategy to enhance ADCs’ functionality within tumors: 1. Increasing ADC potency safely with higher DAR - STRO-0 04: Potential best-in-class exatecan ADC targeting tissue factor with broad, pan-tumor potential (IND planned 2H 2025) 2. Dual-payload ADCs to overcome resistance and deliver safe antitumor activity 3. iADCs: combining delivery of cytotoxin and immune stimulator Lead Opportunity: Ovarian Cancer (Fast T rack Designation) o REFRαME-O1 Registrational Study; ongoing - Bevacizumab-Luvelta Combo Phase 1b; expansion data 1H25 Additional Luvelta Opportunities o CBF/GLIS2 Pediatric AML Registrational Study; ongoing (Orphan and Rare Pediatric Disease designations) - Non-Small Cell Lung Cancer Phase 2; data 2025 - Endometrial Cancer; evaluating expansion options Significant Near- and Long-term Opportunities for Broad Pipeline of Precisely Designed ADCs Luvelta Pipeline-in-a-Product Potential Next-Generation ADCs: Delivering Three INDs Over Next Three Years - Registrational Studies Completed commercial scale 4000 L run; Largest cell -free manufacturing run to date Cell-Free Platform has One-of-A-Kind ADC Design Capabilities to: • Improve safety profile • Enable higher dosing for enhanced efficacy • Broaden addressable patient population
Page 5
NON CONFIDENTIAL 5 5 Well Capitalized with Strong Business Development Track Record Validating Cell-Free Platform 1. Based on cash, cash equivalents and marketable securities held by Sutro as of September 30, 2024. 2. Includes payments and equity investments received through September 30, 2024. Up to $60M in milestones + WW royalties on potential non-PCV future product candidates STRO-003 (ROR1 ADC) preclinical program for solid and hematological malignancies Preclinical immunostimulatory ADCs Exclusive license to luvelta in Greater China Phase 2/3 vaccines for invasive pneumococcal disease Up to ~$824M in milestones + WW royalties Up to ~$423M in milestones per product candidate + WW royalties + U.S. profit sharing option Up to ~$355M in milestones + 10-year royalties on sales in Greater China Up to $250M in potential payments tied to various return thresholds Purchased 4% royalties on potential future net sales of Vaxcyte PCV products Over $2 Billion Potential Future Milestones plus Royalties ~$388M (1) in cash, cash equivalents & marketable securities ~$975M (2) Funding generated from our collaborators
Page 6
NON CONFIDENTIAL 6 Luveltamab Tazevibulin (Luvelta)
Page 7
NON CONFIDENTIAL 7 Source: Modified from Dumontet, C et al., Nat Rev Drug Discov 2023; 22, 641–661. ICD – Immunogenic cell death Receptor internalization Hemiasterlin- derivative toxic payload delivery Luvelta: Precisely Designed Tubulin Inhibitor ADC with Potential to Address a Broader Patient Population of FRα-expressing Cancers Key Features Driving Luvelta’s Best-in-class Potential Hemiasterlin payload • Tubulin inhibitor • High potency & ICD • High bystander killing • Low Pg-p substrate
Page 8
NON CONFIDENTIAL 8 Luvelta: Promising Clinical Activity in All FRα-Expressing Indications Evaluated FRα expression assumptions for ovarian: ≥25% TPS (80% of pts, internal data); endo: ≥25% TPS (41% of pts8); NSCLC: ≥1% TPS (30% of pts, internal data). Sources: 1. Sutro internal estimates, data on file. 2. DRG reports. 3. Cancer Statistics in Japan 2023 ganjoho.jp. 4. SEER data and data explorer. 5. American Cancer Society Cancer Facts and Figures, 2023. 6.Deloitte Consulting & IQVIA custom projects for Sutro, 2022. 7. European Cancer Information System (ECIS), accessed Dec 2023. 8. Brown Jones M, et al., Int J Cancer. 2008 Oct 1;123(7):1699-703. 9. Eidenschink Brodersen L, et al. Leukemia. 2016;30(10):2077-2080. 10. Smith, JL et al. Clinical Cancer Research. vol. 26,3 (2020): 726-737. FRα is broadly expressed across many cancer types, with significant potential for future follow-on opportunities - Registrational Studies Estimated Annual Incidence in FRα-Expressing Patient Populations (U.S., Europe and Japan) Ovarian Cancer: ~69K Status: REFRαME-O1 Registrational Study Bevacizumab combo Phase 1b expansion data expected 1H 2025 NSCLC, Adenocarcinoma: ~108K Status: Phase 2 initial data expected 2025 Pediatric AML with CBF/GLIS2 AML mutation: ~100 per market Status: Registrational study ongoing Endometrial Cancer: ~71K Status: Evaluating patient expansion through IST
Page 9
NON CONFIDENTIAL 9 Luvelta: Opportunity to be First Therapy for ~80% of PROC Patient Population with Lower TPS≥25% Threshold Luvelta Potentially Doubles the Addressable PROC Patients Approved ADC Luvelta Patients with Platinum-Resistant Ovarian Cancer >75% FRα Expression, 2+/3+ staining intensity ≥25% FRα Expression, any staining intensity 35% 80% • Luvelta has demonstrated clinical activity in PROC patients with FRα ≥25% of any staining intensity (1+,2+,3+) • T reatment eligibility is driven by FRα biomarker test • Due to high frequency of testing of FR⍺ in OC, patient expression level may be known with initial tissue diagnosis PROC: Platinum Resistant Ovarian Cancer 1 – Luvelta eligibility based on TPS level in REFRaME trial; FDA Approved ADC eligibility based on TPS level in Elahere approved label 2 – AbbVie ImmunoGen Acquisition - Slides on the AbbVie IR website,November 30, 2023
Page 10
NON CONFIDENTIAL 10 Significant Opportunity for Luvelta to Become Best-in-Class, With Clear Commercial Path Approved FRα ADC Luvelta Addressable Patient Population 35% of PROC patients 2 (TPS of ≥75% FRα, 2+ staining intensity) 80% of PROC patients 1 TPS ≥25% FRα at any staining intensity T olerability Profile Black box warning on ocular toxicity Neutropenia well- managed (no febrile neutropenia); no safety signals for ocular damage, pancytopenia, or ILD Sales Projected to generate ~$471 million in sales for 2024, with expectations of growth to over $700 million in 20253 REFRαME-O1 registrational study ongoing, positioned for accelerated approval application mid-2027 PROC: Platinum Resistant Ovarian Cancer 1 – Luvelta eligibility based on TPS level in REFRaME trial; FDA Approved ADC eligibility based on TPS level in Elahere approved label 2 – AbbVie ImmunoGen Acquisition - Slides on the AbbVie IR website,November 30, 2023 3 – FactSet consensus estimates as of January 7, 2025 Luvelta: Addresses broader market Improved tolerability profile Clear commercial path Approved tubulin FRα ADC validates approach, but approval is restricted to subset of patients with high expression and comes with ocular black box warning.
Page 11
NON CONFIDENTIAL 11 Registrational Strategy Supported by Clinical Data from ~100 Patients Partial response 3 in 5.2, 2 in 4.3, 2 in <=2.9, and 1 in >=5.6mg/kg Starting dose, Q3W ≤ 2.9 mg/kg 4.3 mg/kg 5.2 mg/kg ≥ 5.6 mg/kg 20% -30% Data as of Nov 8, 2023. Ovarian Cancer Patients Total (N = 99) Platinum Sensitive 21 (21.2%) Platinum Resistant 78 (78.8%) Number of prior lines of therapy (Median) 3.0 Previous Therapies, n (%) bevacizumab 72 (72.7%) PARP Inhibitor 70 (70.7%) Maximum Reduction in Tumor T arget Lesions in RECIST-Evaluable Patients (N=92 Evaluable)
Page 12
NON CONFIDENTIAL 12 REFRαME-O1 Enrollment Progressing Ahead of Internal Projections Phase 3 randomized part 2 enrollment tracking ahead of internal projections Over 200 sites expected to be active by mid-2025 Active partnerships with GOG, ENGOT, APGOT to organize and align patients and recruitment efforts Australia Canada Israel South Korea United States Sources: clinicaltrials.gov NCT05870748. Internal Sutro data on file. Active Countries Trial Sites/Enrollment Singapore New Zealand Planned Countries* Aust ria Belgium Czech Republic Finland Germany Hungary France Bulgaria Italy Poland Sweden Switzerland Argentina Brazil United Kingdom Spain Ireland *All planned countries to be active in 1H2025, except for Finland
Page 13
NON CONFIDENTIAL 13 REFRαME-O1 Dose Optimization: Confirms Luvelta’s Robust Response in PROC Patients with FRα ≥25%, Selected Starting Dose of 5.2 mg/kg *Data as of Aug 16, 2024 Topline Results from Efficacy Evaluable Patients (5.2 mg/kg group; N = 25)* Results reaffirm Luvelta’s potential to benefit 8 out of 10 PROC patients Luvelta is positioned for an Accelerated Approval application in mid-2027 • ~1/2 of the patients treated were ineligible for an approved FRα-targeting ADC • 88% of patients received prior bevacizumab • Achieved ORR of 32%, which includes 1 PR that confirmed post data extraction • Consistent response rates across all levels of FRα expression ≥25% • High disease control rate of 96% • No new safety findings • Neutropenia well-managed; Grade 3+ neutropenia occurred in 32%, no febrile neutropenia • No safety signals for ocular damage, pancytopenia, or Interstitial Lung Disease Patient Profile Efficacy Profile Safety Profile
Page 14
NON CONFIDENTIAL 14 • 23 patients enrolled to-date, including PSOC & PROC • All-comers trial – no FRα cut-off requirements Luvelta Demonstrated Compelling Anti-Tumor Activity and Manageable Safety Profile In Lower and Variable FRα Expressing Tumors Bevacizumab Combo in Ovarian Cancer RAM AML1 NSCLC N = 17 N = 25 Preclinical Median PFS 8.3 months; 55.6% ORR at RP2D Anti-tumor activity irrespective of prior bevacizumab therapy or FRα expression Data from expansion cohort expected in 1H25 Meaningful clinical responses, including complete remission and prolonged overall survival Well tolerated and can be given as out-patient Registrational trial ongoing Single dose and combination with PD-1 blockade demonstrated anti-tumor activity Phase 2 trial ongoing Luvelta EAP mOS not reached 1.0 0.8 0.6 0.4 0.2 0.0 0 2 4 6 8 10 12 14 Survival Time Since The First Dose of IP or Relapse (Months) Survival Probability Historic Luvelta Historical (N=26) mOS = 6.1 months Overall Survival for Children who Received Luvelta as Non-Fractionated Dosing Regimen (N=21) NSCLC PDX model with single dose Luvelta monotherapy RP2D, recommended Phase 2 dose; TPS, tumor proportion score. 1 - These data were generated by the treating physicians and collected and enabled for presentation by Sutro. Ovarian Cancer source: 1 – ESMO 2024 Poster 749P: Luveltamab tazevibulin, an anti-folate receptor alpha antibody-drug conjugate, in combination with bevacizumab in patients with recurrent high-grade epithelial ovarian cancer: STRO-002-GM2 phase 1 study * - FRα missing for one patient RAM AML source: Dec 2023 ASH poster “Anti-leukemic Activity of Luveltamab Tazevibulin (LT, STRO-002), a Novel Folate Receptor-α (FR-α)-targeting Antibody Drug Conjugate (ADC) in Relapsed/Refractory CBFA2T3::GLIS2 AML.” NSCLC source: Internal Sutro preclinical data on file. censored Study Days Vehicle 5 mg/kg luvelta (single dose) 10 mg/kg luvelta (single dose) 800 600 400 200 0 0 20 40 60 80 100 Tumor size (mm 3) Phase 1b Response Data (Presented at ESMO 2024)1 Phase 2 Expansion Cohort
Page 15
NON CONFIDENTIAL 15 STRO - 004 & Next - Gen ADCs Leveraging Cell - Free Platform to Deliver Three INDs Over the Next Three Years
Page 16
NON CONFIDENTIAL 16 Wider Therapeutic Index Achieved with Sutro’s Cell-free ADC Platform Adapted from Gerber et al, mAbs, 2023 MTD – Maximum Tolerated Dose; MED – Minimum Effective Dose MTD ADC MED ADC TI MTD ADC MED ADC TI Increasing ADC Potency Safely with Higher DAR of Exatecan ADCs (DAR 8, 12, 16) Next Generation Immuno-Oncology with Immune Activation & Cytotoxins: iADCs Combining Payloads to Overcome Resistance with Dual-Payload: ADC2 3 1 2 Linker & payload design Click chemistry Site specific conjugation Antibody engineering Key Sutro Technologies to Improve ADCs Outside the Tumor Focused R&D Strategy – Make ADCs Better Inside the Tumor
Page 17
NON CONFIDENTIAL 17 XpressCF® Platform has Unique ADC Performance Capabilities Over Other Topo1 ADC Platforms DAR>8 Beta-Glu Linker ADC2/ Dual LPs iADC/ iSAC Site Specific Fc Silent Bispecific HT Screening Abbvie AstraZeneca Daiichi Sankyo Dualitybio Genequantum Genmab Gilead Hansoh Hengrui Kelun Lilly Medilink Merck KGaA Pfizer LP – linker payloads; iSAC – immune stimulating antibody conjugate; HT – high throughput; Comparison of Topo1i ADC Platforms (Selected)
Page 18
NON CONFIDENTIAL 18 STRO-004: Next Generation Tissue Factor-Targeting Exatecan/Topo1 ADC with Enhanced Therapeutic Potential Optimally Designed for I mproved Clinical Benefits, Enhanced Stability, Potency and Tumor Selectivity • Exatecan payload: Clinically validated with potent activity, bystander and reduced susceptibility to resistance • Improved potency to reach low copy number patients • β-glucuronidase linker: Engineered for enhanced tumor selectivity and hydrophilicity • Optimized drug performance: High DAR8 and improved conjugation positioning • Widened therapeutic/ safety index: Driving higher drug exposure and efficacy than 1 st gen TF ADCs; designed to minimize interference with coagulation cascade • Optimized to reduce risk of neutropenia, bleeding, and ocular toxicities IND filing and first-in-human studies planned for 2H 2025 Increased Tolerability Leads to Enhanced Drug Exposure 1,350 81.1 STR0-004 Approved TF ADC ADC (ug/mL) Cmax 170,880 3,440 STR0-004 Approved TF ADC ADC (h*ug/mL) AUClast 50x
Page 19
NON CONFIDENTIAL 19 Tissue Factor is Broadly Expressed Across Multiple Solid Tumor Indications, Presenting Opportunity for Pan-Tumor Targeting • TF expression has been associated with poor disease prognosis and increased metastatic properties • Clinical validation of TF in cervical cancer, along with early signs of activity in HNSCC, pancreatic cancer, and multiple other solid tumors with significant unmet needs Broad Opportunity for TF in Many Solid Tumors of Significant Unmet Need HNSCC – head and neck squamous cell carcinoma NSCLC – non-small cell lung cancer
Page 20
NON CONFIDENTIAL 20 STRO-004 DAR8 Exatecan Achieved Sustained Tumor Regressions in Xenograft Models of NSCLC and HNSCC at Low Doses 0 20 40 60 0 250 500 750 1000 1250 1500 Days post treatment Tumor volume (mm3) Detroit562 Growth Curves 0 10 20 30 40 50 0 250 500 750 1000 1250 1500 Days Post Dose Tumor Volume (mm3) H1975 Growth Curves Vehicle STRO-004 DAR8, 0.125 mg/kg STRO-004 DAR8, 0.25 mg/kg STRO-004 DAR8, 0.5 mg/kg STRO-004 DAR8, 1 mg/kg Days Post Treatment Tumor Volume (mm3) Lung (TF+++) Head and Neck (TF++) Tumor Volume (mm3) Days Post Treatment
Page 21
NON CONFIDENTIAL 21 Eye Inflammation Skin Toxicities STRO-004 Demonstrated Reduced Platform and On-target Toxicity Due to Site Specific Conjugation and Beta Glu Linker-Payload Technology STRO-004 Tolerability Profile vs. Approved aTF ADC Approved aTF ADC (DAR4-MMAE)STRO-004 (DAR8-exatecan)
Page 22
NON CONFIDENTIAL 22 Dual-Payload ADCs: Combining Payloads to Overcome Resistance Reduced Toxicity Reduced Clinical Complexity Simultaneous Payload Delivery Overcome Resistance Mechanisms Potential Advantages of Dual-Payload ADC Approach
Page 23
NON CONFIDENTIAL 23 Dual Payload ADC (Topo1i + anti-Tubulin) Displayed Enhanced In Vivo Efficacy in Ovarian Cancer 0 20 40 60 80 100 0 500 1000 1500 Days Post Dose Relative Tumor Volume (%) IGROV-1 - Tumor Growth Vehicle control Trastuzumab DAR4 MTI ADC (5 mg/kg) Trastuzumab DAR8 Topo1i ADC (5 mg/kg) Trastuzumab DAR8 Topo1i + DAR4 MTI dpADC (5 mg/kg) 0 20 40 60 80 100 0 25 50 75 100 Days Post Dose Percent Survival IGROV-1 - Survival 0 20 40 60 80 100 0 25 50 75 100 Days Post Dose Percent survival IGROV-1 - Time to Tumor Quadrupling
Page 24
NON CONFIDENTIAL 24 iADC: Combines Tumor-Targeted Delivery of a Cytotoxin and Immune Stimulator Strategic Partnership with Astellas to Deliver a New Treatment Option for Cold Tumors and Patients Unresponsive to Existing Cancer Immunotherapies Combining a cytotoxin and immune modulator gives potential to: • Act alone by stimulating the immune system and priming new populations of immune cells • Synergize with other immune therapies that remove inhibitory signals on the immune system (e.g. checkpoint inhibitors) • Address hard-to-treat cancers by activating a robust anti-tumor immune response
Page 25
NON CONFIDENTIAL 25 Novel Mechanism of Action Differentiates iADC from Other Immunotherapies Sutro iADC STING / TLR ISAC PD-1 / PDL-1 CAR-T Cells Vaccine Molecule Targeted and homogeneous Chemo Mixed ADC Ab Biologic Biologic Opportunity: Risk Combine ICD with innate agonists (TLR, STING, etc.) Non-targeted, issues with TI Requires Fc effector Limited tumor types, small tumors Safety concerns Ag selection challenge FcγR meditated uptake into myeloid Direct tumor cell killing Tumor antigen presentation Priming and activation of Antigen Presenting Cells T-cell recruitment to tumor Mechanisms to achieve anti-tumor immunity Sutro iADCs bridge innate and adaptive immunity to provide broad protection in a single molecule STING – stimulator of interferon genes; TLR- toll-like receptor; immunogenic cell death – Undesirable
Page 26
NON CONFIDENTIAL 26 Boehringer Ingelheim BioXcellence Collaboration: Established First-in-class Cell-free Manufacturing Capabilities at Commercial Scale 26 First-ever manufacturing of a cell-free ADC to large-scale GMP production, marking an industry milestone • Modular approach with faster discovery cycle times • Leverages non-natural amino acids to precisely attach proteins to chemicals in ways that cell-based methods cannot achieve • All 4,500 L batches of luvelta antibody produced at Boehringer's facility met clinical quality standards • Over 3,000 patients have been treated to date with biologics made using Sutro’s cell-free technology Proprietary Cell-free XpressCF® Platform Advantages:
Page 27
NON CONFIDENTIAL 27 Broad Pipeline Driven by Cell-free Technology PROGRAM MODALITY/TARGET INDICATION DISCOVERY PRECLINICAL PHASE 1/1B PHASE 2 PHASE 3/ REGISTRATIONAL WORLDWIDE OR GEOGRAPHIC PARTNER SUTRO-LED PROGRAMS Luveltamab tazevibulin (Luvelta, STRO-002) FRα Antibody-Drug Conjugate (ADC) Ovarian Cancer Ovarian Cancer (bevacizumab comb o) Endometrial Cancer CBF/GLIS2 Pediatric AML NSCLC STRO-004 Tissue Factor ADC Solid Tumors Next Generation ADCs ADC2 + Solid Tumors PARTNER PROGRAMS VAX-24 24-Valent Conjugate Vaccine Invasive Pneumococcal Disease VAX-31 31-Valent Conjugate Vaccine Invasive Pneumococcal Disease STRO-003 ROR1 ADC Solid Tumors & Hematological Cancers Undisclosed Programs Immunostimulatory ADCs (iADCs) Cancers (Greater China Rights)