CONTESSA TRIO: A Multinational, Multicenter, Phase 2 Study of Tesetaxel plus 3 Different PD-(L)1 Inhibitors in Patients with Metastatic Triple-Negative (TNBC) and Tesetaxel Monotherapy in Elderly Patients with HER2- Metastatic Breast Cancer (MBC) Sara Tolaney1, Joanne Blum2, Igor Bondarenko3, Arlene Chan4, Noshir DaCosta5, Yin Hsun Feng6, Yann Izarzugaza7, Sung-Bae Kim8, Mei-Ching Liu9, Maria Eva Peréz Lopéz10, Mafalda Oliveira11, Samuel Guan Wei Ow12, Michel Pavic13, Hope Rugo14, Lee Schwartzberg15, Agostina Stradella16, Stew Kroll17, Joseph O'Connell17, Thomas Wei17, Elizabeth Mittendorf18 1Dana-Farber Cancer Institute, Boston, MA; 2Baylor University Medical Center, Texas Oncology, US Oncology, Dallas, TX; 3Komunalnyi Zaklad Miska Bahatoprofilna, Dnipropetrovsk, Ukraine; 4Breast Cancer Research Centre-Western Australia and Curtin University, Perth, Australia; 5North Shore Hematology Oncology Associates, Stony Brook, NY; 6Chi Mei Medical Center, Tainan City, Taiwan; 7Hospital Universitario Fundación Jiménez Díaz, Madrid, Spain; 8Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea; 9Koo Foundation Sun Yat-Sen Cancer Center, Taipei, Taiwan; 10A Coruña Universitario Hospital, La Coruña, Spain; 11Hospital Universitari Vall d'Hebron, Barcelona, Spain; 12National University Cancer Institute, Singapore, Singapore; 13McPeak-Sirois Group, Centre Hospitalier Universitaire de Sherbrooke (CRCHUS), Sherbrooke Quebec, Canada; 14University of California San Francisco Comprehensive Cancer Center, San Francisco, CA; 15West Cancer Center, Memphis, TN; 16Institut Catala d'Oncologia Hospital Duran i Reynals, Barcelona, Spain; 17Odonate Therapeutics, Inc., San Diego, CA; 18Brigham and Women’s Hospital, Boston, MA

Background Study Design (Cohort 1) Study Design (Cohort 2)

• regimens for patients with MBC that offer robust efficacy while preserving patient quality of life are needed • Nivolumab and pembrolizumab (PD-1 inhibitors) and atezolizumab (a PD-L1 inhibitor) are approved for the • Tesetaxel plus a PD-(L)1 inhibitor may provide patients with an alternative treatment option requiring fewer a All patients must meet full eligibility criteria as stipulated in the Study ODO-TE-B301 Protocol • Tesetaxel is a novel with several properties that make it unique (Table 1), including: treatment of multiple types of cancer infusion center visits than the currently approved atezolizumab plus nab- dosing regimen (Figure 4) Figure 6: Study Design – Oral administration with a low pill burden • Atezolizumab, in combination with nab-paclitaxel, was recently approved in the U.S. for the treatment of 11 – A long (~8-day) terminal plasma half-life (t ) in humans, enabling infrequent, once-every-3-weeks (Q3W) dosing (Figure 1) metastatic TNBC (Figure 3) 1/2 Multinational, Multicenter – No observed hypersensitivity reactions – Preclinical evidence of central nervous system (CNS) penetration; and Figure 3: Atezolizumab Plus Nab-paclitaxel PFS Results in Patients with Figure 4: Infusion Schedules for Atezolizumab Plus Nab-paclitaxel and a – Significant activity against chemotherapy-resistant tumors PD-L1 Expression ≥ 1% PD-(L)1 Inhibitor Plus Tesetaxel • More than 600 patients have been treated with tesetaxel in clinical studies Target Enrollment

Table 1: Tesetaxel’s Unique Pharmacologic Figure 1: Pharmacokinetic Profiles of Properties Paclitaxel and Tesetaxel Tesetaxel Monotherapy Elderly (≥ 65 years old) patients 27 mg/m2 once every 3 weeks with HER2 negative MBC Molecule Paclitaxel Tesetaxel 10000 N=40 (Potential expansion to

Nitrogen- N=40 containing N=60) functional Paclitaxel GI (Potential expansion to N=60) groups 100 50 7.5 ng/mL8,9 Structure 1 Taxane Taxane Taxane core core core Tesetaxel GI50 0.6 ng/mL8,9 Substantially effluxed 0.01 • Primary Endpoints: ORR Yes Yes No by P-gp pumpa • Secondary Endpoints: PFS, DoR, OS Paclitaxel Oral bioavailability in 0.0001 • Exploratory Endpoints: ORR by receptor subtype, CNS ORR, CNS DoR 8%1 18%2 56% 80 mg/m2 Q3/4W5 preclinical studies Tesetaxel b 3 4 Solubility (µg/mL) 0.3 0.5 41,600 0.000001 27 mg/m2 Q3W7 Mean Mean Plasma Concentration (ng/mL) Table 5: Key Eligibility Criteriaa Terminal plasma 11 hours5 11 hours6 193 hours7 0.000000011E-08 half-life in humans (t1/2) 0 200 400 600 800 1000 Patients are ELIGIBLE if they: Patients are NOT ELIGIBLE if they: a The P-glycoprotein (P-gp) efflux pump mediates gastric absorption as well Time (hours) Figure 5: Study Design as chemotherapy resistance GI50=concentration of drug required to inhibit growth by 50%; 1. Have HER2 MBC; de novo patients are allowed 1. Have previously received chemotherapy for MBC b At pH conditions similar to gastric fluid Q3/4W=once per week for 3 of 4 weeks; Q3W=once every 3 weeks 2. Have a disease-free interval of at least 12 months 2. Have HER2 positive breast cancer • In a multicenter, Phase 2 study, 38 HER2 negative, HR positive MBC patients receiving tesetaxel as a single agent achieved Multinational, Multicenter Arm A after completion of systemic neoadjuvant or adjuvant a confirmed response rate of 45% (44% in patients with no prior taxane exposure and 45% in patients with prior taxane Tesetaxel 27 mg/m2 + chemotherapy, if applicable exposure) with a low incidence of Grade ≥3 neuropathy and Grade 2 alopecia (Figure 2)10 Nivolumab 360 mg once every 3 weeks 3. Received a taxane in the (neo)adjuvant setting or are n=30 (Potential expansion to n=50) taxane-naïve Figure 2: Study TOB203 Tumor Change from Baseline in Target Lesions for HR Positive Target Enrollment 4. Have CNS metastases (allowed but not required) Patients Receiving Tesetaxel Q3Wa,b 5. Have had prior endocrine therapy with or without a Arm B cyclin-dependent kinase 4/6 inhibitor (allowed but not Tesetaxel 27 mg/m2 + required) unless endocrine therapy is not indicated; Adult (≥ 18 years old) patients with previously any prior targeted therapies are permitted; there is no

1:1:1 1:1:1 Pembrolizumab 200 mg once every 3 weeks limit on the number of prior endocrine therapies untreated, metastatic TNBC n=30 (Potential expansion to n=50) N=90 a All patients must meet full eligibility criteria as stipulated in the Study ODO-TE-B202 Protocol (Potential expansion to N=150) Randomization Arm C Conflicts of Interest Tesetaxel 27 mg/m2 + Atezolizumab 1,200 mg once every 3 weeks ST has served as an advisor/consultant to Novartis, Eli Lilly, Pfizer, Merck, AstraZeneca, Eisai, Puma, Genentech, Immunomedics, Nektar, Tesaro and NanoString; JB has served as an advisor/consultant to Pfizer, Medivation and Novartis; AC has served as an advisor/consultant to • Primary Endpoints: Objective response rate (ORR) and progression-free survival (PFS) n=30 (Potential expansion to n=50) • Secondary Endpoints: Duration of response (DoR) and overall survival (OS) Novartis, Pfizer and Puma. AC has also participated in a Speaker’s Bureau for Prime Oncology and received expense reimbursement from Pierre Fabre; M-CL has served as an advisor/consultant to Roche; MO has received Honoraria from Roche and served as an advisor/consultant to • Exploratory Endpoints: ORR and PFS by PD-L1 expression, CNS ORR, CNS DoR Roche, GSK and Puma. MO has also received expense reimbursement from Roche, Pierre Fabre, Novartis, GP Pharma and Grunenthal; HR has received expense reimbursement from Genentech, Pfizer, Puma, Mylan, Daiichi and MacroGenics. HR has received Honoraria from Celltrion, and other publication support from Pfizer, Novartis and Roche; MP has received Honoraria from Celgene, Janssen, Novartis and Takeda and has a a Nadir change based on sum of the diameters Table 3: Key Eligibility Criteria Table 4: Comparison of 3 Approved PD-L1 Diagnostic Assays served as an advisor/consultant to Celgene, Novartis, Amgen, Takeda, Roche, Bristol Myers Squibb and Pfizer. MP has also received expense b Includes 38 enrolled patients; 1 patient was not evaluated for response reimbursement from Taiho and Bayer; LS has served as an advisor/consultant to Helsinn, Merck, Heron Therapeutics, Pfizer, AstraZeneca and Patients are ELIGIBLE if they: Patients are NOT ELIGIBLE if they: PD-(L)1 Amgen. LS has participated in a Speaker’s Bureau for Coherus and Puma; SK is an employee in a leadership role and has stock in Odonate; JO PD-L1 Inhibitor is an employee in a leadership role and has stock in Odonate and also has also been employed in a leadership role with stock in InVentiv; TW is Table 2: Ongoing Tesetaxel Clinical Studies 1. Have HER2 negative MBC; de novo patients are 1. Have previously received chemotherapy for Nivolumab Pembrolizumab Atezolizumab Assay an employee in a leadership role and has stock in Odonate; EM has served as an advisor/consultant to Amgen, AstraZeneca, Genentech, allowed MBC Genomic Health, Merck, Peregrine Pharmaceuticals, Sellas Lifesciences and TapImmune. Study Name Phase N Patient Population Regimen 2. Have a most recent biopsy that is HR negative 2. Have HER2 positive breast cancer Approved Assay for Dako 28-8 Exploratory Exploratory HER2 negative, HR 3. Have a disease-free interval of at least 12 3. Have had prior PD-(L)1/PD-L2 or CTLA-4 Nivolumab References Tesetaxel + vs. CONTESSA 3 600 positive MBC with prior months after completion of systemic neoadjuvant inhibitor capecitabine or adjuvant chemotherapy, if applicable 1. Shanmugam et al, Drug Development and Industrial Pharmacy 2015;41(11):1864- taxane 4. Have certain autoimmune or inflammatory 1876 Copies of this poster 4. Received a taxane in the (neo)adjuvant setting or conditions, active infections, or are using Approved Assay for HER2 negative, HR Dako 22C3 Exploratory Exploratory 2. McEntee et al, Veterinary and Comparative Oncology 2003;1(2):105-112 obtained through QR are taxane-naïve certain immunosuppressive agents Pembrolizumab CONTESSA 2 2 125 positive MBC with no prior Tesetaxel + capecitabine 3. Montaseri, Taxol: Solubility, Stability and Bioavailability 1997 (Quick Response) and/or taxane 5. Have CNS metastases (allowed but not required) 4. Bharate et al, Bioorganic & Medicinal Chemistry Letters 2015;25(7):1561-1567 text key codes are for 5. Tan et al, British Journal of Cancer 2014;110(11):2647-54 personal use only and may 6. Have an adequate, newly obtained or archival Approved Assay for Tesetaxel + nivolumab vs. Ventana SP142 Exploratory Exploratory 6. Taxotere (docetaxel) prescribing label not be reproduced without core or excisional biopsy of a not-previously- Atezolizumab CONTESSA TRIO 2 90-150 Metastatic TNBC tesetaxel + pembrolizumab vs. 7. Lang et al, 2012 ASCO Annual Meeting, Journal of Clinical Oncology 2012;20 (15 written permission of the irradiated tumor lesion obtained since completion Cohort 1 tesetaxel + atezolizumab supp):2555 authors. This Study is of any systemic therapy for central determination sponsored by Odonate • Each of the 3 PD-(L)1 inhibitors being combined with tesetaxel has an approved PD-L1 diagnostic assay 8. Shionoya et al, Cancer Science 2003;94(5):459-66 of PD-L1 status. Metastatic tumor biopsy 9. Trock et al, Journal of the NCI 1997;89(13):917-31 Therapeutics, Inc. • Tumors from each patient will be tested with all 3 PD-L1 diagnostic assays Elderly (≥ 65 years old) preferred; PD-L1 status determination is not 10. Seidman et al, Journal of Clinical Oncology 36, 2018 (suppl; abstr 1042; poster CONTESSA TRIO 2 40-60 Tesetaxel monotherapy • Efficacy results for each of the 3 PD-(L)1 inhibitor combinations will be assessed for correlation with the with HER2 negative MBC required for enrollment or randomization #123) Please contact [email protected] with Cohort 2 results of each of the 3 approved PD-L1 diagnostic assays a All patients must meet full eligibility criteria as stipulated in the Study ODO-TE-B202 Protocol 11. Tecentriq (atezolizumab) prescribing label any questions or comments.