AZD0466 active in small cell lung cancer patient models

AZD0466 active in small cell lung cancer patient models Melbourne, Australia; 20 April 2023 : Starpharma (ASX: SPL, OTCQX: SPHRY) today announces AZD0466 results from a preclinical study in small cell lung cancer (SCLC) patient- derived xenograft (PDX) models. Starpharma’s partner, AstraZeneca, presented these results overnight at the American Association for Cancer Research (AACR) Annual Meeting. AZD0466 is a highly optimised dendrimer nanoparticle formulation of AstraZeneca’s dual Bcl-2/xL inhibitor, AZD4320, which utilises Starpharma’s DEP ® technology and is being developed by AstraZeneca under their multi-product DEP® license with Starpharma. AZD0466 is the first candidate under Starpharma’s multi -product license with AstraZeneca whereby Starpharma is eligible to receive development, launch and sales milestones, in addition to royalties. The AACR Annual Meeting is one of the world’s largest cancer research conferences, bringing together thousands of investigators, scientists, and clinical researcher s to discuss new and significant observations. SCLC is an aggressive form of lung cancer with relatively few treatment options and a 5-year survival rate of only ~ 7%1. The results from this latest research in SCLC presented by AstraZeneca at the AACR Annual M eeting showed that Bcl-2/xL inhibition has therapeutic potential in SCLC: • AZD0466 was active in 50% of SCLC models, resulting in tumour regression in 33% of models. • Dual Bcl-2/xL inhibitor AZD0466 outperformed marketed Bcl-2 inhibitor venetoclax2 in 60% of SCLC models. • Notably, AZD0466 was also active in models resistant to the current standard-of-care treatment for SCLC: platinum/etoposide chemotherapy. In addition to the preclinical data in SCLC, the poster presented by AstraZeneca at the AACR Annual Meeting also included newly released clinical trial data from AstraZeneca’s first-in- human study of AZD0466 in patients with advanced solid tumours (NCT04214093). In this clinical trial (NCT04214093), 9 patients with adrenal carcinoma, anal cancer, bile duct cancer, bladder/urethral cancer, colorectal cancer, lung cancer, pancreatic cancer, and sarcoma were treated with AZD0466. Of the 9 patients treated wi th AZD0466 in this trial, efficacy signals were observed in 33% of these patients who achieved stable disease for periods of up to 5.5 months. AZD0466 is also currently being evaluated in patients with advanced haematological malignancies ( NCT04865419) and non-Hodgkin lymphoma ( NCT05205161). 333 patients have been treated with AZD0466 across the advanced sol id tumour and advanced haematological malignancy trials. The AstraZeneca poster included updated clinical data from the ongoing global Phase 1/2 clinical trial in patients with advanced haematological malignancies (NCT04865419). This trial has now treated 24 4 patients at doses up to 3600mg, with patient treatment ongoing and 1 Gazdar A et al. Nat Rev Cancer 2017 2 Venetoclax is an oral medication, sold under the brand names Venclexta and Venclyxto, used to treat adults with chronic lymphocytic leukemia, small lymphocytic lymphoma, or acute myeloid leukemia. 3 Anderson C L et al. AZD0466, a dual BCL-2/XL targeting nanomedicine, is active in small cell lung cancer models [abstract]. In: Proceedings of the 114th Annual Meeting of the American Association for Cancer Research; 2023 April 14-19; Orlando, FL. Philadelphia (PA): AACR; 2023. Abstract nr 6150/12 4 Patient data as at 24 January 2023 2 further dose escalations planned. This trial continues to progress well, with no dose -limiting toxicities reported to date and with initial clinical activity observed through reduction of bone marrow blasts following AZD0466 treatment and a mean treatment duration of 4.4 months . This Phase 1/2 trial in patients with acute myeloid leukaemia (AML) or acute lymphoblastic leukaemia (ALL) continues to enroll at 18 sites across the United States, Europe, Asia and Australia, with additional sites planned. These new preclinical and clinical results for AZD0466 were presented in a poster presentation by AstraZeneca at the AACR Annual Meeting overnight. The poster and corresponding abstract are appended and will be available on Starpharma’s website: www.starpharma.com. In addition to the poster presentation, AZD0466 featured at AstraZeneca’s booth at the AACR Annual Meeting, as part of their haematology development portfol io, through an interactive display highlighting AstraZeneca’s clinical pipeline and portfolio. Starpharma’s dendrimer drug delivery technology, known as DEP ®, is used to enhance the therapeutic properties of drugs to improve solubility, efficacy, pharmacokinetics, targeting, and to reduce certain toxicities. Starpharma has established partnerships with three of the world’s largest pharmaceutical companies – AstraZeneca, MSD, and Genentech – and has also developed three clinical-stage anticancer products based on its DEP® technology, with others in preclinical development. Dr Jackie Fairley, Starpharma CEO, commented: “It is exciting to see AstraZeneca continue to invest in the preclinical and clinical development of their licensed DEP® product, AZD0466. This AZD0466 poster presentation in Small Cell Lung Cancer at one of the world’s largest cancer research conferences – the American Association for Cancer Research – adds to the growing body of preclinical and clinical data AstraZeneca is generating for this innovative anti- cancer product, which was developed using Starpharma’s DEP® technology. “AZD0466 is already being trialed globally in patients with advanced l eukaemias and non- Hodgkin lymphoma. The preclinical and clinical results presented at AACR are encouraging and the positive data in SCLC may lead to an expanded market opportunity for AZD0466 and, importantly, bring a potentially more efficacious product to patients in need. We look forward to seeing further data and clinical progress for AZD0466.” About AZD0466 and Starpharma’s multi-product DEP® license with AstraZeneca AZD0466 is a highly optimised dendrimer nanoparticle formulation of AstraZeneca’s dual Bcl- 2/xL inhibitor, AZD4320, which utilises Starpharma’s DEP® technology and is being developed by AstraZeneca under their multi -product DEP® license with Starpharma. AZD0466 is in a novel class of oncology drugs called dual Bcl -2/xL inhibitors which seek to overcome drug resistance which occurs in treatment with BcL-2- specific inhibitors including venetoclax. AZD0466 allows for efficient delivery of AstraZeneca’s dual B cl-2/xL inhibitor, with an optimised release profile also designed to reduce the potential for toxicities associated with dual Bcl -2/xL inhibition. Dual Bcl -2/xL inhibition with AZD0466 also has the potential for broader activity than the marketed Bcl-2-specific inhibitor, venetoclax (Venclexta®). AZD0466 is the first candidate under Starpharma’s multi -product license with AstraZeneca. Starpharma is eligible to receive development, launch and sales milestones, in addition to royalties. To date, Starpharma has received US$7M in milestones for AZD0466, with the potential to receive milestones of up to US$124M, plus royalties. 3 About Starpharma Starpharma Holdings Limited (ASX:SPL, OTCQX:SPHRY) is a biopharmaceutical company, focussed on the development of pharmaceutical and medical products for unmet patient needs, including in the areas of oncology and infectious diseases. Starpharma’s innovative technology is based on proprietary polymers called dendrimers, which are precise, synthetically manufactured, nanoscale molecules. The unique properties of dendrimers – including their size, structure, high degree of branching, polyvalency, and water solubility – are advantageous in medical and pharmaceutical applications. Starpharma uses its dendrimer technology to develop novel therapeutics and to improve the performance of existing pharmaceuticals. Starpharma’s portfolio includes multiple clinical stage oncology products, which utilise its Dendr imer Enhanced Product (‘DEP®’) drug delivery technology; and marketed products, including VIRALEZE ™ and VivaGel® BV, which utilise SPL7013, a proprietary dendrimer with antimicrobial properties. Starpharma’s DEP® drug delivery platform is being used to enhance the effectiveness of existing and novel therapies and to reduce drug-related toxicities through controlled and specified drug delivery. In addition to Starpharma’s internal DEP ® programs, Starpharma has multiple DEP ® partnerships with international biopharmaceutical companies including AstraZeneca (oncology); MSD (antibody drug conjugates); Chase Sun (anti - infectives); and other world leading pharmaceutical companies. Due to the broad applicability and o ptionality of Starpharma’s DEP® platform, partnered DEP® programs have the potential to generate significant future milestones and royalties. Starpharma’s topical antiviral nasal spray, VIRALEZE™, is now registered in more than 30 countries*, including in Europe, in the UK, and in Southeast Asia. Starpharma’s novel non- antibiotic vaginal gel, VivaGel® BV, for treatment of bacterial vaginosis (BV) and prevention of recurrent BV, is registered in more than 45 countries, including in the UK, in Europe, in Southeast Asia, South Africa, Australia and New Zealand. * Note: VIRALEZE™ is not approved for use or supply in Australia. Starpharma.com | Twitter | LinkedIn Media: Sumit Media Grant Titmus Mob: +61 419 388 161 [email protected] Starpharma Holdings Limited Dr Jackie Fairley, Chief Executive Officer Justin Cahill, CFO and Company Secretary +61 3 8532 2704 [email protected] 4-6 Southampton Crescent Abbotsford Vic 3067 Disclosure This ASX Announcement was authorised for release by the Chairman, Mr Rob Thomas. 4 Forward Looking Statements This document contains certain forward-looking statements, relating to Starpharma’s business, which can be identified by the use of forward-looking terminology such as “promising”, “plans”, “anticipated”, “will”, “project”, “believe”, “forecast”, “expected”, “estimated”, “targeting”, “aiming”, “set to”, “potential”, “seeking to”, “goal”, “could provide”, “intends”, “is being developed”, “could be”, “on track”, or similar expressions, or by express or implied discu ssions regarding potential filings or marketing approvals, or potential future sales of product candidates. 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Small cell lung cancer (SCLC) AZD0466 drives regressions in SCLC patient-derived models AZD0466 is under clinical investigation Summary •Small cell lung cancer is an aggressive, heterogenous malignancy ◦ Accounts for ~15% of all lung cancer cases in the US1 ◦ Five (5)-year survival is <7%1 •Currently all patients receive same upfront chemotherapy (platinum/etoposide) •SCLC is comprised of distinct transcriptional subtypes requiring unique targeted therapeutic approaches2,3 ◦ ASCL1 (A), POU2F3 (P), NEUROD1 (N), and YAP (Y) •BCL-2 is highly expressed in A- and P- subtypes ◦ Subtypes represent ~51% (A) and ~7% (P) of SCLC patients2 •We evaluated the potential of AZD0466, a dual BCL-2/XL inhibitor, in SCLC models •BCL-2/XL inhibition with AZD4320 and AZD0466 is active in SCLC models •Efficacy is enriched in models representing A and P subtypes of SCLC •AZD0466 is currently under clinical investigation and has been well-tolerated in doses up to 3600 mg •Preclinical efficacy is observed at clinically achievable exposures 2 Acknowledgements: Emily Rowe, Kaitlyn Beyfuss AZD0466, a dual BCL-2/XL targeting nanomedicine, is active in small cell lung cancer models Courtney L. Andersen1, Giulia Fabbri1, David Jenkins1, Zumla Cader2, Shring Sharma3, Areya Tabatabai1, Srividya Balachander1, Jordan Roebuck4, Melanie Galvin4, Kathryn Simpson4, Caroline Dive4, Jordi Rodon Ahnert5, Jamal Saeh1 AZD0466: a dual BCL-2/XL inhibitor Presented at the American Association of Cancer Research Annual Meeting | Orlando, FL | April 2023 A. A. References: 1. Gazdar A et al. Nat REv Cancer 2017, 2. Gay CM et al. Cancer Cell 2021, 3. Rudin CM et al. Nat Rev Cancer 2019. 4. Simpson KL et al. Nat Cancer 2020. 5. Arslan et al. Abstract #4094 ASH Annual Meeting 2022. AZD0466 efficacy is enriched in subtype-A patient-derived models A- and P-subtype SCLC cell lines have higher BCL-2 and are more sensitive to AZD4320 ¹Oncology R&D, AstraZeneca, Waltham, MA; ²Oncology R&D, AstraZeneca, Cambridge, ENG, United Kingdom; ³Oncology R&D AstraZeneca, South San Francisco, CA; ⁴Cancer Research UK Cancer Biomarker Centre, University of Manchester, Manchester, ENG, United Kingdom; ⁵MD Anderson Cancer Center, Houston, TX 0 10 20 30 0 500 1000 1500 2000 MEDI-SCLC-11 Efficacy Days on study Tumor Volume (mm3) GeoMean + SE Vehicle AZD0466 10 mg/kg IV QW AZD0466 34 mg/kg IV QW AZD0466 103 mg/kg IV QW SCL C-02 SCL C-04 SCL C-07 SCL C-14 SCL C-08 SCL C-12 SCL C-03 SCL C-13 SCL C-09 SCL C-06 SCL C-10 SCL C-05 SCL C-11 LU-5223 -100 -50 0 50 100 Tumor Volume Percent growth vs vehicle AZD0466 103 mg/kg Venetoclax 100 mg/kg Etoposide/Platinum -150 -100 -50 0 50 100 150 0.0 0.5 1.0 1.5 2.0 Percent change in Tumor Vol Normalized BCL-2 protein levels P < 0.0001 -150 -100 -50 0 50 100 150 0 2 4 6 Percent change in Tumor Vol log2 RPKM BCL2 P < 0.0001 Preclinical PK Clinical PK 0 20 40 60 0.01 0.1 1 10 100 1000 Hours Post Dose AZD4320 Plasma concentration AZD0466 10 mg/kg IV - Total AZD0466 34 mg/kg IV - Total AZD0466 103 mg/kg IV - Total AZD0466 103 mg/kg IV - Released AZD0466 34 mg/kg IV - Released AZD0466 10 mg/kg IV - Released Patient-derived xenografts (PDX) Tumor volume reduction correlates with BCL2 mRNA and protein expression Preclinical SCLC efficacy observed at clinically achievable doses B. 50 100 150 200 -100 0 100 200 300 400 CDX 20P (28)* Days post randomisation Relative Tumour Volume Vehicle AZD0466 11 mg/kg QWx4 AZD0466 34 mg/kg QWx4 AZD0466 70 mg/kg QWx4 *Post-chemotherapy relapsed model 20 40 60 80 100 -100 0 100 200 300 400 CDX 17 Days Post Randomisation Relative Tumour Volume B. 6 6 24 48 6 2448 6 2448 0 5 10 15 20 MEDI-SCLC-11 Cleaved caspase-3 Fold CC3 induction / vhc Hours post dose -Response in 12 / 24 models (PDX + CDX) -Regression in 8 / 24 -Dual BCL-2/XL inhibition more active than selective BCL-2 inhibition with venetoclax -AZD0466 active in models resistant to Platnium/Etoposide (SOC) AZD4320 is active in SCLC cell lines CDX 17P (1 9) CDX 8P ( 11) CDX 4 CDX 20 CDX 8 CDX 22 CDX 18P (2 7) CDX 18 CDX 20P (2 8) CDX 17 -100 -50 0 50 100 200 300 400 Circulating tumor cell-derived xenografts (CDX4) Tumor Volume Percent change fom baseline AZD0466 70 mg/kg AZD0466 can produce prolonged CRs in SCLC models DMS53 CORL95 CORL88 SHP77 NCIH2066 COLO668 NCIH209 NCIH1092 NCIH1963 NCIH1876 NCIH69 CORL279 NCIH1694 NCIH524 DMS273 NCIH82 NCIH446 NCIH526 CORL311 NCIH211 NCIH1048 SW1271 NCIH841 SBC5 NCIH196 DMS114 NCIH1341 ASCL1 NEUROD1 POU2F3 YAP1 BCL2 MYC Log10 IC50 AZD4320 mRNA levels SCLC-A SCLC-N SCLC-P SCLC-Y NE non-NE Model Subtype Response CDX 18 CDX 20 CDX 27 (18P) CDX 28 (20P) LU-5223 SCLC-05 SCLC-06 SCLC-09 SCLC-10 SCLC-11 SCLC-13 SCLC-14 CDX 22* CDX 4* CDX 17 CDX 19 (17P) CDX 11 (8P) CDX 8 SCLC-02 SCLC-03 SCLC-07 SCLC-08 SCLC-04 SCLC-12 ASCL1 NEUROD1 ATOH1 N/D AML, acute myeloid leukemia; ALL, acute lymphocytic leukemia; MDS, myelodysplastic syndrome * Reasonable possibility adverse event was caused by AZD0466, as assessed by the investigator. Graded per CTCAE v5. a. A study of AZD0466 in patients with advanced hematologic or solid tumors (NCT04214093). Data as of 20-Dec-2021. b. A study of AZD0466 monotherapy or combination in patients with advanced hematologic malignancies (NCT04865419)5. Patient treatment is ongoing and only data up to 24-Jan-2023 are captured. Advanced solid tumorsa Advanced hematologic malignanciesb,5 24 patients9 patientsNumber of patients treated Doses administered (range) Disease indication (number of patients) Mean treatment duration Adverse events > Grade 3 related to AZD0466* (number of patients) Adrenal carcinoma (1), anal cancer (1), bile duct cancer (1), bladder/urethral cancer (1), colorectal cancer (1), lung cancer (1), pancreatic cancer (1), sarcoma (2) AML (20), ALL (4), MDS (0) 50 mg to 200 mg 300 mg to 3600 mg 3.4 months 4.4 months Aspartate aminotransferase increased (2), alanine aminotransferase increased (1) Febrile neutropenia (3), thrombocytopenia (1), diarrhea (1), gamma-glutamyl transferase increased (1), platelet count decreased (1) PD SD PR CR Low High Sensitivity A N P Y -3 -2 -1 0 1 2 3 AZD4320 IC50 SCLC cell line subtype Log10 IC50 (µM) N/D: no data on subtype *CDX22 and CDX4 also have high YAP1 expression **ATOH1 represents recently reported subtype⁴ 6 12 18 24 30 36 42 48 10 100 1000 10000 100000 1000000 Time (hr) AZD4320 Plasma Concentration (nM) 20000 2000 4000 6000 AZD0466 600 mg IV - Total AZD0466 600 mg IV - Released AZD0466 300 mg IV - ReleasedAZD0466 300 mg IV - Total AZD0466 1200 mg IV - Total AZD0466 1200 mg IV - Released AZD0466 2400 mg IV - Released 500000 AZD0466 3600 mg IV - Total AZD0466 2400 mg IV - Total AZD0466 3600 mg IV - Released AZD0466 is a novel drug-dendrimer conjugate, where the active moiety, AZD4320, is chemically conjugated to Starpharma’s clinically validated DEP® dendrimer platform Stealth layer prolongs circulation time and improves solubility G5 Poly-L-lysine core AZD0466 dosed intermittently to deliver efficacy while maximizing therapeutic index Session PO.ET06.05 - Cell Death Pathways and Treatment / Molecular Classication of Tumors for Diagnostics, Prognostics, and Therapeutic Outcomes 6150 / 12 - AZD0466, a dual BCL-2/XL targeting nanomedicine, is active in small cell lung cancer models  April 19, 2023, 9:00 AM - 12:30 PM  Section 16 Presenter/Authors Courtney L. Andersen, Giulia Fabbri, David Jenkins, Zumla Cader, Shringi Sharma, Areya Tabatabai, Srividya Balachander, Jordan Roebuck, Melanie Galvin, Kathryn Simpson, Caroline Dive, Jordi Rodon Ahnert, Jamal Saeh AstraZeneca, Waltham, MA,AstraZeneca, Cambridge, United Kingdom,AstraZeneca, South San Francisco, CA,CRUK Manchester Institute, Manchester, United Kingdom,MD Anderson Cancer Center, Houston, TX Disclosures  C. L. Andersen, AstraZeneca Employment, Stock. G. Fabbri, AstraZeneca Employment, Stock. D. Jenkins, AstraZeneca Employment, Stock. Z. Cader, AstraZeneca Employment, Stock. S. Sharma, AstraZeneca Employment, Stock. Gilead Stock. A. Tabatabai, AstraZeneca Employment. S. Balachander, AstraZeneca Employment, Stock. Bristol Myers Squibb Employment. J. Roebuck, None.. M. Galvin, None.. K. Simpson, None.  C. Dive, AstraZeneca Grant/Contract, Other, Honoraria for consultancy and/or advisory boards. Amgen Grant/Contract. Carrick Therapeutics Grant/Contract. Merck AG Grant/Contract, Other, Honoraria for consultancy and/or advisory boards. Taiho Oncology Grant/Contract. Bayer Grant/Contract. Boehringer Ingelheim Grant/Contract, Honoraria for consultancy and/or advisory boards. Roche Grant/Contract. Bristol Myers Squibb Grant/Contract. Novartis Grant/Contract. Celgene Grant/Contract. Epigene Therapeutics Inc Grant/Contract. Angle PLC Grant/Contract. Menarini Grant/Contract. Biocartis Other, Honoraria for consultancy and/or advisory boards. GRAIL Other, Honoraria for consultancy and/or advisory boards. J. Rodon Ahnert, Peptomyc, Kelun Pharmaceuticals/Klus Pharma, Ellipses Pharma, Molecular Partners, IONCTURA Other, Advisory Board. Blueprint Medicines, Black Diamond Therapeutics, Merck Sharp & Dohme, Hummingbird, Yingli, Vall d'Hebron Institute of Oncology/Cancer Core Europe Grant/Contract, Research funding (to institution). Novartis, Spectrum Pharmaceuticals, Symphogen, BioAlta, Pzer, GenMab, CytomX, Kelun-Biotech,  Add to My Itinerary 1 1 1 2 3 1 1 4 4 4 4 5 1 1 2 3 4 5 Takeda-Millenium, GalxoSmithKline, Taiho, Roche Pharmaceuticals, Hummingbird, Yingli Other, Clinical research (to institution). European Society for Medical Oncology Travel. Vall d'Hebron Institute of Oncology/Ministero De Empleo Y Seguridad Social, Chinese University of Hong Kong, Boxer Capital, LLC, Tang Advisors, LLC Other. Bycicle Therapeutics, Merus, Curis, Bayer, AadiBioscience, Nuvation, ForeBio, BioMed Valley Discoveries, Loxo Oncology, Hutchinson MediPharma Other, Clinical research (to institution). Cellestia, Deciphera, Ideaya, Amgen, Tango Therapeutics, Mirati Linnaeus Therapeutics Other, Clinical research (to institution). J. Saeh, AstraZeneca Employment, Stock. Abstract Small cell lung cancer (SCLC) is an aggressive malignancy with critical need for new therapies. While currently treated as a single disease, SCLC is heterogenous, comprised of several transcriptional subtypes. Each of these subtypes has distinct drivers and may warrant unique therapeutic targets. Two potential therapeutic targets for SCLC are the pro-survival proteins BCL-2 and BCL-XL. BCL-2 is overexpressed in ASCL1 (A) and POUF3 (P) subtypes of SCLC. We therefore sought to evaluate ecacy of the dual BCL-2/XL inhibitor AZD0466 in SCLC models and to determine whether transcriptional subtype would predict response. AZD0466 is a novel drug-dendrimer conjugate. The active moiety, AZD4320, is a potent dual inhibitor of BCL-2 and BCL-XL. AZD4320 is covalently conjugated to a 5-generation PEGylated poly-lysine dendrimer through a hydrolytically labile linker to make AZD0466. AZD0466 has been optimized to deliver ecacy while mitigating potential Cmax-driven on-target toxicities of AZD4320. AZD4320 was active (IC50 ≤ 0.1 µM) in 9/27 SCLC cell lines. AZD4320 in vitro sensitivity was enriched in cell lines that represented A and P subtypes of SCLC compared to NEUROD1 and YAP1 subtypes. We next proled AZD0466 in a panel of SCLC patient-derived models: 14 patient-derived xenografts and 10 circulating tumor cell-derived xenografts. AZD0466 monotherapy dosed weekly IV was active in 12/24 SCLC xenografts, driving regressions in 8 models. AZD0466 drove ecacy and cleaved caspase-3 induction in a dose-dependent manner. Similar to in vitro, AZD0466 in vivo ecacy was enriched in subtype-A, driving responses in 10/14 ASCL1 models (7 regression, 3 stable disease). AZD0466 response also correlated strongly with BCL-2 mRNA expression (P<0.0001). AZD0466 outperformed the selective BCL-2 inhibitor venetoclax in 6/10 models. Notably, AZD0466 was active in models resistant to platinum/etoposide chemotherapy, the standard-of-care for SCLC. Together, these data suggest BCL-2/XL inhibition has therapeutic potential in SCLC. AZD0466 is in clinical development. The rst-in- human study treated 9 patients with advanced solid tumors (NCT04214093) at doses from 50-200mg, all of which were well-tolerated. The BOR was SD observed in 3 patients (100mg) with 1 patient receiving treatment for 5.5 months. AZD0466 is now under evaluation in patients with hematologic malignancies (NCT04865419 and NCT05205161). AZD0466 has been dosed in 33 patients up to 2400mg. No DLTs have been reported to date. Initial clinical activity has been observed through reduction of bone marrow blasts following AZD0466 treatment. AZD0466 exhibits linear PK, consistent across solid tumor and leukemia patients. The doses tested are in line with preclinical studies in SCLC. th

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