Exhibit 99.1
PRECISION ONCOLOGY FOR THERAPIES OF TOMORROW PRECISION ONCOLOGY FOR THERAPIES OF TOMORROW Aptose Corporate Presentation NASDAQ: APTO TSX: APS June 27, 2022
Disclosure This presentation does not, and is not intended to, constitute or form part of, and should not be construed as, an offer or i nvi tation for the sale or purchase of, or a solicitation of an offer to purchase, subscribe for or otherwise acquire, any securities, businesses and/or assets of any entity, nor shall it or any par t of it be relied upon in connection with or act as any inducement to enter into any contract or commitment or investment decision whatsoever. This presentation contains forward - looking statements , which reflect APTOSE Biosciences Inc.’s (the “Company”) current expectations, estimates and projections regarding future events, including statements relating to our business strategy, our clinical development plans, our ability to obtain the substantial capital we require, our plans to secure strategic partnerships and to build our pipeline, our clinical trials and their projected timeline, the efficacy and toxicity of our pr odu ct candidates, potential new intellectual property, our plans, objectives, expectations and intentions; and other statements including words such as “anticipate”, “contemplate”, “continue” , “ believe”, “plan”, “estimate”, “expect”, “intend”, “will”, “should”, “may”, and other similar expressions. Such statements constitute forward - looking statements within the meaning of secu rities laws. Although the Company believes that the views reflected in these forward - looking statements are reasonable, such statements invol ve significant risks and uncertainties, and undue reliance should not be placed on such statements. Certain material factors or assumptions are applied in making these forward - lo oking statements, and actual results may differ materially from those statements. Those factors and risks include, but are not limited to, our ability to raise the funds necessary to c ont inue our operations, changing market conditions, the successful and timely completion of our clinical studies including delays, the demonstration of safety and efficacy of our dr ug candidates, our ability to recruit patients, the establishment and maintenance of corporate alliances, the market potential of our product candidates, the impact of competitive products an d p ricing, new product development, changes in laws and regulations, uncertainties related to the regulatory approval process and other risks detailed from time to time in the Compa ny’ s ongoing quarterly filings and annual reports. Forward - looking statements contained in this document represent views only as of the date hereof and are presented for the purpo se of assisting potential investors in understanding the Company’s business, and may not be appropriate for other purposes. The Company does not undertake to upd ate any forward - looking statements, whether written or oral, that may be made from time to time by or on its behalf, except as required under applicable securities legislation. Inv estors should read the Company’s continuous disclosure documents available at www.sedar.com and EDGAR at www.sec.gov/edgar.shtml , especially the risk factors detailed therein. 2
Aptose Biosciences (NASDAQ: APTO) Clinical Stage Oncology Company ᄫ Focused on Precision Medicines Developing highly differentiated oral kinase inhibitors for hematologic malignancies Experienced leadership with deep expertise in kinase inhibitors & orphan diseases Planned value - driving clinical updates through 2022 and cash runway through 2023 LUXEPTINIB (CG - 806) Dual Lymphoid and Myeloid Kinome Inhibitor High value targets in B - cell cancers, AML, and inflammation : BTK, FLT3, LCK, LYN, Others Ongoing parallel dose escalations in patients with B - cell l ymphomas /CLL and AML/MDS Clinically active: anti - tumor activity in high - bar clinical setting of R/R patients → Encouraging data with G3 formulation to reduce drug substance and increase plasma exposure HM43239 O ral Myeloid Kinome Inhibitor ᄫ Clinically Validated for R/R AML Patients Targets high value kinases operative broadly in AML patients : FLT3 WT/MUT , SYK, JAK1/2, cKIT MUT CRs in diverse R/R AML patients: FLT3 ITD/TKD/WT , NPM1 MUT , TP53 MUT , N/K - RAS MUT , MLL, RUNX1, IDH MUT Orphan Drug Designation for AML and Fast Track Designation for R/R AML patients with FLT3 MUT → Now Transitioning to Expansion Trials planned 2H2022 : Dose s and patient populations selected 3
Aptose Leadership Team : Multifaceted Expertise in Therapeutic Development 4 William G. Rice, PhD Chairman, President & Chief Executive Officer Philippe Ledru Sr. VP & Chief Commercial Officer Rafael Bejar , MD, PhD Sr. VP & Chief Medical Officer Fletcher Payne Sr. VP & Chief Financial Officer
Aptose SAB : Distinguished Opinion Leaders with Deep Oncology Expertise 5 Brian J. Druker, MD Pioneer in the field of precision medicine Key Role in development of Gleevec - the first targeted kinase inhibitor for cancer Member, National Academy of Medicine, National Academy of Sciences & American Academy of Arts & Sciences Winner of Karnofsky Award, Lasker Award, Japan Prize in Healthcare and Medical Technology, Tang Prize in Biopharmaceutical Science, Sjöberg Prize Leader of Inter - institutional Beat AML Initiative Michael Andreeff, MD, PhD Renowned hematology specialist Professor of Medicine Paul and Mary Haas Chair in Genetics Chief, Section of Molecular Hematology and Therapy MD Anderson Cancer Center Expert in AML and other hematologic malignancies Expert in drug resistance and drug mechanisms Daniel Von Hoff, MD, FACP Former President of AACR Board Member of ASCO Former Presidential Cancer Advisory Board Physician in Chief, TGen Medical Director of Research for McKesson Specialty Health Chief Scientific Officer for US Oncology Research Professor of Medicine, Mayo Clinic Scottsdale
Aptose Clinical Stage Pipeline: Oral Kinase Inhibitors that Cover a Broad Spectrum of Hematologic Malignancies 6 Program Target Indication Preclinical Phase 1 Proof - of - Concept Phase 2/3 Registrational HM43239 Myeloid Kinome AML Luxeptinib Myeloid Kinome AML, MDS Luxeptinib Lymphoid Kinome B - cell Cancers Phase 1a/b Phase 1a/b • Small molecule kinase inhibitor candidates designed to treat a disease • Confirmed anti - leukemic activity in dose - escalation studies, with expansion studies planned • Orphan hematology programs, with broader optionality into solid tumor indications Phase 1/2
7 HM43239 “239” Oral Myeloid Kinome Inhibitor
HM43239 Proven Clinical Activity in AML Patients with Significant Unmet Needs 8 HM43239 Myeloid Kinome Inhibitor Single Agent Activity 3 doses with CRc and no drug - related SAE Well tolerated No drug - related SAE, QTc toxicities, or CK increases Validated AML Targets FLT3, SYK, JAK1/2, cKIT MUT Accelerated paths to approval CRc in FLT3 - mutated R/R AML FLT3 MUT / failed prior FLT3 inhibitors CRc in FLT3 - unmutated R/R AML FLT3 WT / harboring adverse mutations
AML in the US : Estimated 20,240 new cases and 11,400 deaths in 2021 Continued Unmet Need for More Effective and Safe Therapies 9 Epidemiology US (2021) EU5 (2020) Japan (2021) China (2020) Leukemia Incidence 3 61,090 1 51,820 3 14,600 7 85,400 AML Incidence 20,240 2 16,580 3 a 6,570 7c 31,430 3b 5 - Year Prevalence (Leukemia) (2020) 3 187,560 152,230 41,280 241,750 Mortality (Leukemia) 11,400 (AML) 2 31,690 8,700 7 61,690 a EU5 incidence calculated by applying 32% (AML) on leukemia to obtain incidence of AML 6 b In China, AML accounted for ~36.8% of all leukemias 5 c In Japan, AML accounted for ~45% of all leukemias in 2008 4 Sources: 1. SEER_2021 Leukemia ; 2. SEER 2021 AML ; 3. The Global Cancer Observatory (GLOBOCAN) - IACR (2020) - Projections ; 4 . Chihara et al. Br J Haematol. 2014 ; 5. Chen et al. J Hematol Oncol. 2010: 21 ; 6. Cancer.net ; 7. Ganjoho Cancer Statistics in Japan 2021 *https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7486485/ *https://www.frontiersin.org/articles/10.3389/fonc.2021.649209/full • Most common acute leukemia in adults • 5 - year survival rate of approx . 30 % • Relapsed AML patients have a median life expectancy of < 6 months * with approved therapies • Need new targeted agents to better treat R/R AML patients and to treat resistance to current agents • Need more effective & better tolerated agents to achieve lasting remissions and extend meaningful life
HM43239 Kinase Inhibitory Profile: Predicts Clinical Activity in AML Patients Harboring Mutated FLT3, Unmutated FLT3, and Having a Diverse Collection of Adverse Mutations 10 Potent suppression of driver and compensatory kinases operative in AML • All forms of FLT3 : - ITD, - TKD, - GK mutations and FLT3 - WT • SYK signal transduction kinase • JAK 1/2 signal transduction kinases • cKIT MUT alternative receptor kinases → Serves as a multi drug therapy in a single molecule → Simultaneously disrupts multiple signal transduction pathways that drive AML proliferation and resistance mechanisms Assay Methodology Kinase Mutation Type Activity Binding Affinity (K D , nM) FLT3 WT 0.58 ITD 0.37 D835Y 0.29 D835H 0.4 ITD/D835V 0.48 ITD/F691L 1.3 Inhibition of Kinase Enzyme Activity (IC 50 , nM) FLT3 WT 1.1 ITD 1.8 D835Y 1.0 SYK WT 2.9 JAK JAK - 1 2.8 JAK - 2 6.3 JAK - 2 (V617F) 9.9 c - KIT WT > 500 D816H 3.6 D816V 3.5
HM43239 Suppresses P - FLT3 / P - SYK and the P - STAT / P - ERK Downstream Pathways in AML Cell Lines MV - 4 - 11 MOLM - 14 MV - 4 - 11 MOLM - 14 Confirmation of P - SYK Inhibition by HM43239 with Flow Cytometry in MV - 4 - 11 and MOLM - 14 AML Cells MV - 4 - 11 MOLM - 14 BAF3/ITD HM43239 (nM) HM43239 (nM) HM43239 (nM) Ba/F3 / FLT3 - ITD
HM43239 In Vivo Models Suggest Superior Antitumor Activity and Favorable Tolerability Relative to Established Kinase Inhibitors in AML MOLM - 14 ITD/F691L - MUT AML cells used with an in vivo murine xenograft model: • MOLM - 14 ITD/F691L - MUT is an AML cell harboring the ITD and F691L dual mutant form of FLT3 • Cells resistant to gilteritinib FLT3 inhibitor • HM43239 inhibits SYK and FLT3 harboring the ITD and F691L • HM43239 superior antitumor activity to: • Gilteritinib FLT3i • Entospletinib SYKi • HM43239 monotherapy shows similar efficacy but better tolerated than combination of Gilteritinib plus Entospletinib 12
HM43239 Superior to Gilteritinib in AML Models Conducted in Mice: AML with FLT3 - ITD/F691L Mutations Resistant to Gilteritinib FLT3 Inhibitor 13 HM43239 more potent than gilteritinib : Subcutaneous AML model resistant to gilteritinib Three million MOLM - 14 FLT3 - ITD/ F691L cells were implanted SC in nude mice. Fifteen days later they were randomized by their tumor volume into 3 groups of 5 mice each. The mice were then treated orally QD with either placebo, 30mg/kg HM43239 or 30 mg/kg gilteritinib for 28 days. Statistical analysis utilized two - way ANOVA followed by Sidak’s test. HM43239 more potent than gilteritinib : Orthotopic/Systemic AML model resistant to gilteritinib Mice were administered i.v. MOLM - 14 FLT3 - ITD/ F691L cells and allowed to populate the bone marrow for 7 days, after which d rugs were administered orally QD 14 days. Representative images of IHC were collected using a Dako REAL Envision Detection System (400x) and quantified with a Vectra 3 Pathology Imaging Analyzer (200x images). Positive DAB % = DAB positive area pixel / (Hematoxylin pixel + DAB positive area pixel) × 100. ƒ VC, vehicle control; HM, HM43239 30 mg/kg; Gil, Gilteritinib 30mg/kg. ƒ ns, not significant; * p<0.05, **p<0.01, ***p<0.001, ****p<0.0001 (unpaired t test using GraphPad PRISM®, GraphPad Software)
HM43239 In Vivo Models Suggest Synergy with Inhibitors of DNMT, BCL - 2, or MDM - 2, and Combinatorial Optionality in AML HM43239, in subcutaneous xenograft, superior efficacy to Gilt or Aza alone and combines effectively with each against MOLM - 14 ITD/F691L - MUT AML HM43239, in subcutaneous xenograft, superior efficacy to Venetoclax alone and combines effectively with Ven against MV4 - 11 AML HM43239, in circulating AML model, superior efficacy to dasanutlin MDM2i alone and combines effectively with Idasanutlin against MOLM - 14 ITD/F691L - MUT 14
HM43239 Preclinical Data Position for Broad Clinical Success in AML Patients • Positioned as Superior to Other FLT3 Inhibitors • Inhibits all forms of FLT3 • Kills AML cells and treats AML disease in animals resistant to other approved FLT3 inhibitors • Positioned as a FLT3/SYK/JAK Inhibitor for AML – More than a FLT3 Inhibitor • SYK inhibitor, JAK inhibitor, and c - KIT inhibitor • “Combination therapy in one molecule” that suppresses multiple key targets simultaneously • Positioned to Achieve Broad Therapeutic Window • Well tolerated with oral activity in animal models • Antitumor activity in animal models across multiple safe dose levels • Favorable Pharmaceutical and CMC Properties • Stable as drug substance and drug product • Orally administered and absorbed efficiently • Current tablet presentation appears acceptable for commercialization 15
HM43239 Phase 1/2 Study in R/R AML: Ongoing Dose Escalation & Dose Exploration 16 PART A : DOSE ESCALATION PART B : DOSE EXPLORATION Cohort 6 200 mg QD Ongoing Cohort 5 160 mg QD Completed Cohort 4 120 mg QD Completed Cohort 3 80 mg QD Completed Cohort 2 40 mg QD Completed Cohort 1 20 mg QD Completed 160 mg QD 9 Treated → 20 Planned 80 mg QD 20 Treated 120 mg QD 12 Treated → 20 Planned Data filtered through: 26APR2022 Study ongoing across several cohorts: the dose escalation cohort of 200 mg and the dose exploration cohorts of 120 mg and 160 mg are currently enrolling. Favorable safety profile: N o drug related SAE or death and no observed relation between delta - QTc throughout the trial . And no DLT through 160 mg dose level
HM32239 Swimmers’ Plots of R/R AML Patients Dosed Through Cut - off Date of 31May2022 17 4 8 12 16 20 24 28 32 36 40 44 48 52 56 60 64 Weeks on Study Treatment Safety Follow-up 200 mg 160 mg 120 mg 80 mg 40 mg 20 mg 20 20 40 80 80 80 80 120 120 120 160 160 160 160 200 200 200 200 1 2 3 4 5 6 7* 8 9 10 11 12 13 14 15 16 17 18 WT ITD WT TKD WT WT WT WT WT WT ITD ITD WT ITD WT WT ITD WT M/71 M/48 F/43 M/72 M/65 F/40 M/60 M/61 F/35 M/79 F/75 M/62 M/83 M/30 M/59 M/82 F/48 F/52 (mg) Dose Pt# Status FLT3 Age Sex/ 4 8 12 16 20 24 28 32 36 40 44 48 52 56 60 64 Weeks on Study Treatment Safety Follow-up On Study Treatment 200 mg 160 mg 120 mg 80 mg 40 mg 20 mg 80 80 80 80 80 80 80 80 80 80 80 80 80 80 80 80 120 120 120 120 120 120 120 120 120 160 160 160 160 160 19* 20 21 22 23 24* 25 26* 27 28 29 30 31 32* 33 34 35 36 37* 38 39 40 41 42* 43 44 45 46 47 48* TKD ITD WT ITD/TKD WT ITD WT ITD TKD WT ITD WT WT WT WT WT TKD ITD ITD WT ITD WT ITD ITD WT ITD/TKD WT WT ITD WT F/67 M/51 F/72 F/50 M/80 M/51 F/53 M/50 F/65 M/51 F/52 F/59 F/45 F/63 F/42 M/67 M/84 M/83 F/54 F/18 M/49 F/72 M/75 F/49 F/77 M/67 F/73 F/59 M/61 M/55 (mg) Dose Pt# Status FLT3 Age Sex/ 4 8 12 16 20 24 28 32 36 40 44 48 52 56 60 64 Weeks on Study Treatment Safety Follow-up On Study Treatment 200 mg 160 mg 120 mg 80 mg 40 mg 20 mg 80 120 80 80 160 120 80 80 80 80 160 160 120 200 80 80 80 120 80 120 200 120 80 160 40 120 120 160 80 160 160 200 80 80 20 120 80 120 80 80 160 120 120 80 160 20 200 80 7* 42* 20 26* 12 37* 32* 24* 27 21 11 14 40 16 19* 29 23 8 25 39 18 9 30 45 3 41 43 13 4 44 48* 17 6 31 2 10 28 36 33 34 47 35 38 22 46 1 15 5 WT ITD ITD ITD ITD ITD WT ITD TKD WT ITD ITD WT WT TKD ITD WT WT WT ITD WT WT WT WT WT ITD WT WT TKD ITD/TKD WT ITD WT WT ITD WT WT ITD WT WT ITD TKD WT ITD/TKD WT WT WT WT M/60 F/49 M/51 M/50 M/62 F/54 F/63 M/51 F/65 F/72 F/75 M/30 F/72 M/82 F/67 F/52 M/80 M/61 F/53 M/49 F/52 F/35 F/59 F/73 F/43 M/75 F/77 M/83 M/72 M/67 M/55 F/48 F/40 F/45 M/48 M/79 M/51 M/83 F/42 M/67 M/61 M/84 F/18 F/50 F/59 M/71 M/59 M/65 (mg) Dose Pt# Status FLT3 Age Sex/ PART A : DOSE ESCALATION PART B : DOSE EXPLORATION Composite Swimmers’ Plot All patients dosed through data cut - off date of 31May2022 Swimmers’ Plots of Patient Study Status All patients in Part A (dose escalation) and Part B (dose exploration)
HM43239 Demonstrates Dose - Dependent PK and Target Engagement 18 Plasma inhibitory activity (PIA) Assay Measures the ability of patient plasma to inhibit phospho - FLT3 in MOLM - 14 reporter cell line FINDINGS: PIA was dose - dependent with up to 90% phospho - FLT3 inhibition at dose levels ≥ 80 mg. Plasma PK Daily administered oral doses of 20, 40, 80, 120, 160 and 200mg. Plasma samples not available for all patients to date and all timepoints to date. FINDINGS: Generally, dose - related increase in plasma exposures PK Parameter Mean ± SD
LLOQ = 0.001 µM 0.0001 0.001 0.01 0.1 1 10 M e a n H M 4 3 2 3 9 C o n c e n t r a t i o n ( µ M ) 0.0519 0.5191 5.191 51.91 519.1 5191 M e a n H M 4 3 2 3 9 C o n c e n t r a t i o n ( n g / m L ) 0 1 2 3 4 6 8 10 24 32 48 Nominal Time (hours) 200 mg (n=4)160 mg (n=8)120 mg (n=12)80 mg (n=19)40 mg (n=1)20 mg (n=2) HM43239 Phase 1/2 Study in R/R AML: Pharmacokinetic Properties Following a Single Dose or at Steady State 19 Mean Plasma PK Concentrations (+SD) by Dose Cohort (Semi - log Scale) Single Dose Mean Plasma PK Concentrations (+SD) by Dose Cohort (Semi - log Scale) Multiple Doses / Steady State Data cut - off: 26APR2022 LLOQ = 0.001 µM 0.001 0.01 0.1 1 10 M e a n H M 4 3 2 3 9 C o n c e n t r a t i o n ( µ M ) 0.5191 5.191 51.91 519.1 5191 M e a n H M 4 3 2 3 9 C o n c e n t r a t i o n ( n g / m L ) 0 1 2 3 4 6 8 10 24 Nominal Time (hours) 200 mg (n=3)160 mg (n=6)120 mg (n=12)80 mg (n=16)40 mg (n=1)20 mg (n=1)
HM43239 Patients Who Achieved a Clinical Response to Date in Phase 1/2 Study of R/R AML Patients 20 Abbreviation: CR, complete response; CRi, complete response with incomplete hematologic recovery; CRp , complete response with incomplete platelet recovery; HSCT, hematopoietic stem cell transplantation; NE, not evaluable; PD, pro gressive disease; PR, partial remission. Note: 'Ongoing' means treatment is still ongoing; 'Remain Alive' indicates patients’ status in follow - up after treatment termina tion; The right arrow at the end of horizontal bar indicates patients are still on study, whereas without the right arrow ind ica tes patients discontinued from study. Note: Each response assessed at a regular visit is considered to have started 1 cycle before the assessment; however, the sta rt of the response is considered the integer part of (study day/28) if the response occurred at the End of Treatment visit. * Indicates patients who received prior FLT3 inhibitors, including gilteritinib and/or midostaurin. Indicates Death 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 Duration of Treatment in Cycle S1408 S2220 S1301 S2203 S2211 S2212 S2216 ID Patient Death ITD* ITD* TKD* WT ITD ITD WT mutation FLT3 120 mg 120 mg 80 mg 80 mg 80 mg 80 mg 80 mg Treatment CR NE HSCT/Remain Alive PR Refractory Remain Alive CRi CRp CR PD Remain Alive CRi HSCT/Remain Alive Refractory CRi CR HSCT/Remain Alive CRi CR CRi HSCT/Remain Alive CRi Ongoing 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 Duration of Treatment in Cycle S1408 S2220 S1301 S2203 S2211 S2212 S2216 ID Patient Death ITD* ITD* TKD* WT ITD ITD WT mutation FLT3 120 mg 120 mg 80 mg 80 mg 80 mg 80 mg 80 mg Treatment CR NE HSCT/Remain Alive PR Refractory Remain Alive CRi CRp CR PD Remain Alive CRi HSCT/Remain Alive Refractory CRi CR HSCT/Remain Alive CRi CR CRi HSCT/Remain Alive CRi Ongoing NPM1 DNMT3A KRAS NPM1 DNMT3A PTPN11 TP53 IDH2 SRSF2 MLL - PTD RUNX1 NRAS RUNX1 RUNX1 SF3B1 RB1 Important Mutations * * * HSCT Underway NRAS BCOR U2AF1 SETBP1 CRi 160 mg WT 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 Duration of Treatment in Cycle S1408 S2220 S1301 S2203 S2211 S2212 S2216 ID Patient Death ITD* ITD* TKD* WT ITD ITD WT mutation FLT3 120 mg 120 mg 80 mg 80 mg 80 mg 80 mg 80 mg Treatment CR NE HSCT/Remain Alive PR Refractory Remain Alive CRi CRp CR PD Remain Alive CRi HSCT/Remain Alive Refractory CRi CR HSCT/Remain Alive CRi CR CRi HSCT/Remain Alive CRi Ongoing New CRi reported this week at 160 mg Ongoing • Data filtered through: 26APR2022 : Includes additional CRi after Cut - off date with FLT WT /U2AF1 MUT Patient HSCT Planned
HM43239 AML Patients with Best Clinical Responses to Date Observed 7 CRc and 1 PR in Diverse and Challenging Patient Populations 21 R/R AML FLT3 Mutated FLT3 Un - mutated FLT3 - ITD FLT3 - ITD FLT3 - ITD Prior Mido /Gilt FLT3 - WT FLT3 - WT Normal Cytogenetics Abnormal Cytogenetics Abnormal Cytogenetics NPM1 DNMT3A KRAS NPM1 DNMT3A PTPN11 TP53 IDH2, SRSF2 CR i 80mg HSCT CR 80mg HSCT CR 80mg HSCT CRi 120mg During Cycle 6 Began HSCT PR 120mg 4 Cycles FLT3 - ITD Prior Mido MLL - PTD RUNX1 CR 80mg 14 Cycles NRAS RUNX1 FLT3 - D835V Prior Mido /Gilt RUNX1, SF3B1, RB1 CR 80mg HSCT Normal Cytogenetics Normal Cytogenetics Normal Cytogenetics Normal Cytogenetics FLT3 - WT Normal Cytogenetics NRAS BCOR U2AF1 SETBP1 CRi 160mg HSCT Planned • Data as of June 2, 2022 : Includes additional CRi after Cut - off date with FLT WT /U2AF1 MUT Patient
HM43239 Safety and Efficacy Data Revealed a Broad Therapeutic Window • Safety Profile Favorable to Date ― No drug related SAE ― No drug related deaths ― No drug related AE of elevated CK ― No drug related AE of QT prolongation – No observed relation between D QTc and dose ― No DLT up to 160 mg and one DLT of muscle weakness ( not rhabdomyolysis) at 200 mg • Identified a Therapeutic Range and Broad Therapeutic Window ― Safely achieved efficacy at 3 separate dose levels (80 mg, 120 mg, 160 mg) with no DLT ― Demonstrated broad therapeutic range across safe dose levels ― Safety profile supports combination therapy with other agents • Study Continuing A cross Several Cohorts ― D ose exploration cohort of 120 mg currently enrolling and plan ned for a total of 20 patients ― D ose exploration cohort of 160 mg currently enrolling and plan ned for a total of 20 patients ― Dose escalation at 200 mg dose level planned to continue 22 Data filtered through: 26APR2022
HM43239 Teachings from Phase 1 Guide the Planned Expansion Clinical Studies • Current Dose Escalation/Dose Exploration Phase 1 Trial in R/R AML Patients — Demonstrated CRc in FLT3 - Mutant AML and received Fast Track Designation in FLT3 - Mutant R/R AML — Selected 3 Expansion Doses (80 mg, 120 mg, 160 mg) and Patient Populations for Expansion Trials — Continue Exploration of Molecular Subgroups (Genotypes ) for potential Fast Track and News Flow • Transitioning to Expansion Trials in AML Patients as Prelude to Registrational Trials — Plan 120 mg as Primary Single Agent Expansion Dose with 80 mg and 160 mg as bracketing doses — Plan FLT3 Mutated R/R AML (supported by Fast Track Designation ) — Plan FLT3 - Unmutate d R/R AML (with Adverse Mutations) — Plan Single Agent in FLT3 - Mutated and FLT3 - Unmutated to begin 2H2022 — Plan Combination (239+Ven) in FLT3 - Mutated and FLT3 - Unmutated to begin 1H2023 23
HM43239 + Venetoclax HM43239 single agent (≥ 50% with prior FLT3i ) HM43239 Next Step Planned as Phase 1 Expansion Trials (2H2022) to Provide Data Intended to Support Registrational Studies Group Assignment * R/R AML Patient Stratification ARM 1 FLT3 - Mutated ( - ITD, - TKD, - GK) +/ - prior FLT3i exposure Primary : • Safety and tolerability • Confirm HM43239 single agent RP2D • Select HM43239 candidate RP2D in combination with venetoclax • Select HM43239 candidate R2PD dose in combination with venetoclax and HMA Secondary : • CR c rate (CR + CR h + CR p + CR i ) • Best response rate (CR c + PR) • Duration of response (DOR) • Overall survival (OS) Key Objectives ARM 2 FLT3 - WT (Unmutated) + Adverse Mutations Treatment Group HM43239 + Venetoclax HM43239 single agent (enriched for TP53 - mut or CK) HM43239 + Ven + HMA Once doublet HM43239 dose is established *Patients are randomly assigned to single, doublet, or triplet combination groups based on the open slots available in each group. Group Assignment * 24
Major Objectives and AML Target Populations Sought for HM43239 25 1 R/R AML FLT3+ post FLT3 inhibitor : Limited treatment options for patients 2 R/R AML FLT3+ through combination: Build upon standard of care for patients in combination with with BCL2i and/or HMAs 3 R/R AML FLT3 - Unmutated with adverse mutations: Most patients have limited treatment options, especially if they have received BCL2i and HMAs as frontline treatment Phase 1/2 Phase 3 1L unfit AML FLT3+ patients: Provide superior treatment option for untreated not eligible for high dose chemotherapy 4 1L fit AML FLT3 - Unmutated: Provide superior non high dose chemotherapy option 5 Registrational trial in FLT3+ R/R AML post FLT3i (Accelerated Approval) Registrational Trial in FLT3 - Unmutated R/R AML (Accelerated Approval) Primary FLT3+ R/R AML Untreated unfit FLT3+ AML Untreated fit FLT3 - Unmutated AML 6 High safety & tolerability suggest potential for use in maintenance therapy following HSCT and preferred partner for oral multi - drug combination therapy
HM43239 Overall Response Rate (7 CRc and 1 PR) to Date in Phase 1 as a Single Agent in R/R AML Patients 26 Abbreviation: CR, complete remission; CRc, composite complete remission; CRp, complete remission with incomplete platelet rec ove ry; CRi, complete remission with incomplete hematological recovery; PR, partial remission. Note: efficacy evaluable patients include all patients with at least 80% drug compliance during Cycle 1 or who had reported a DL T during Cycle 1, and who reported relevant data for efficacy interpretation such as bone marrow assessment, CBC counts, reas on for treatment termination. [1] Overall response includes CRc and PR. [2] CRc includes CR, CRh, CRp and CRi. [3] The reported prior FLT3 inhibitors include gilteritinib, midostaurin and soranfenib . Mutation Status All Patients Evaluable Patients N = 45 Patients Number Responder s Response Rate N = 41 Patients Number Responders Response Rate FLT3+ 20 5 25% 19 5 26.3% FLT3+ with prior FLT3i 7 3 42.9% 7 3 42.9% FLT3 - WT 25 3 12% 22 3 13.6% TP53+ 4 1 25% 3 1 33.3% Overall Response Rate for ”All Patients” and “Evaluable Patients” Receiving ≥ 80mg HM43239 — Findings represent a snapshot in time: The reported safety, tolerability, PK, PD and efficacy findings reported herein represent the data available at this time and may change as additional patients are assessed and more data are collected. — The “Evaluable Patients” removes those non - evaluable patients who did not have a response evaluation and had no other evidence indicating refractory disease in the peripheral blood. — Most (6 of 7) CRc patients went to HSCT and cannot be evaluated for transfusion independence assessment. — Analysis Date: 06 June 2022
27 Targets Constellation of Kinases Important in Myeloid Cancers • Potent inhibitor of kinases associated with malignant transformation and resistance • Highly active in vivo against FLT3 internal tandem duplication ( ITD ), resistance - conferring tyrosine kinase domain mutations ( TKD ) , and gatekeeper mutations ( F691 ) • Highly active on SYK , JAK1/2 and mutant forms of c - KIT HM43239 Clinically Validated, Once Daily, Oral Myeloid Kinome Inhibitor Program Goals for 2022 Supporting Rapid Development • E xploring additional adverse genotypes for sensitivity • Provide r olling presentation of clinical findings throughout 2022 • Plan to i nitiate Expansion Trial as single agent 2H2022 • Plan to i nitiate Expansion Trial as combination 1 H2023 • Planning for registrational studies Clinical Validation Supports Path of Rapid Development for AML Patients • FLT3 - Mutated Patients — CRc in patients with mutated FLT3 — Including ITD and D835 TKD mutations — Including those who failed prior FLT3 inhibitors (midostaurin and gilteritinib) — Received FDA Fast Track in FLT3 MUT R/R AML • FLT3 - Unmutated Patients — CRc in patients with unmutated FLT3 — CRc in patients harboring diverse mutations : NPM1, DNMT3A, N/KRAS, MLL, TP53, IDH2, U2AF1, RUNX1, Others • Broad Therapeutic Window — Well tolerated across three active doses supports combination therapy with other agents
28 Luxeptinib Oral Lymphoid & Myeloid Kinome Inhibitor
Luxeptinib: Atypical, Dual Lymphoid and Myeloid Kinome Inhibitor 29 Inhibits WT and all mutant forms of BTK Inhibits WT and all mutant forms of FLT3 May avoid rapid emergence of drug resistance Mutation Agnostic Robust Safety Profile Simultaneously suppresses multiple oncogenic signaling pathways Avoids kinases that negatively impact safety Generally, well tolerated in clinical studies to date Inhibits h igh value targets : BTK, FLT3, CSF1R, PDGFR α , TRK, AURK Only agent to potently inhibit the validated BTK and FLT3 In development for the treatment of both lymphoid & myeloid hematologic cancers Unique Kinome Targeting
30 Published three peer reviewed research articles illustrating the potential of Luxeptinib for application to multiple indications: AML Lymphomas Inflammation Autoimmunity
Luxeptinib: Ongoing Phase 1a/b Study in Heavily Pretreated B - cell Malignancies 31 Cohort 6 900 mg Q12H Completed Cohort 5 750 mg Q12H Completed Cohort 4 600 mg Q12H Completed Cohort 3 450 mg Q12H Completed Cohort 2 300 mg Q12H Completed Cohort 1 150 mg Q12H Completed Dose Escalation Phase • Patients administered oral capsules, twice daily on a 28 - day cycle • Plan to perform 7 dose levels • Planned expansion cohorts • Accelerated titration design • Additional patients may be enrolled ( back filling ) at dose levels previously declared safe • Intra - patient dose escalation is allowed if higher dose is safe in 3 or more patients Objectives Ongoing Phase 1 a/b, open - label, single arm, multicenter, 3 + 3 dose - escalation clinical study (NCT03893682). Primary objectives: • Assess safety and tolerability of luxeptinib (CG - 806) • Determine recommended Phase 2 dose (RP2D) Key secondary objectives: • Assess PK profile and PD activity • Obtain preliminary evidence of antitumor activity • Characterize the bioavailability (BA) of G2 vs. the original G1 formulations G3 Following completion of Cohort 6 with original G1 formulation, patients enrolled to receive single dose of new G3 formulation in addition to G1 at Q12H
Luxeptinib: Swimmers’ Plot of Heavily Pretreated Patients with R/R B - Cell Malignancies Treated with Luxeptinib 32 4 8 12 16 20 24 28 32 36 40 44 48 52 56 60 64 Weeks on Study Treatment Safety Follow-up On Study Treatment 900 mg (Cohort 6) 750 mg (Cohort 5) 600 mg (Cohort 4) 450 mg (Cohort 3) 300 mg (Cohort 2) 150 mg (Cohort 1) 450 450 750 450 150 750 600 600 750 750 450 450 300 750 900 900 750 600 450 450 600 450 600 450 600 900 900 600 750 900 900 450 750 750 5 10* 22 9* 1 21 15 31* 16 26 6 23* 2 20 28 27 25 30* 7 8* 24 3 13 11* 12 29 32** 14 17 33** 34** 4 19 18 NHL NHL NHL CLL/SLL CLL/SLL NHL CLL/SLL CLL/SLL CLL/SLL CLL/SLL CLL/SLL NHL CLL/SLL CLL/SLL NHL NHL NHL NHL NHL NHL CLL/SLL NHL NHL NHL CLL/SLL NHL CLL/SLL NHL CLL/SLL NHL CLL/SLL NHL CLL/SLL CLL/SLL (mg) Dose Pt# Type Data Cut - off Date of 31 May 2022
FL DLBCL CLL RT CLL CLL SLL MCL SLL FL MCL WM * DLBCL SLL CLL DLBCL * FL * CLL FL CLL 5 3 3 5 713 2 2 43 4 67 12 4 2 2 2 3 25 3 3 5 713 2 2 43 4 67 12 4 2 2 2 3 2 IBR IBR IBR IBR IBRIBR IBR IBR IBR IBRIBR IBR IBR IBR IBRIBR IBR IBR IBR IBR 26 27 8 12 13 16 24 20 29 6 5 28 21**22 9 15 25 10 31 23 Patient ID -50 -30 -10 10 30 50 70 150 % S P D C h a n g e f r o m B a s e l i n e # Lines of Prior Therapies Prior IBR Treatment * Treatment Ongoing 900 mg750 mg600 mg450 mgDose Assignment*** Note: IBR = Ibrutinib Note: Only patients with post-screening assessments are shown on plot **WM patient(s) measuring % IgM ***Dose level shown from time of disease assessment, if at least 1 cycle of doses received at this level Source: Z:\SASShare\CG-806\CG-806-01\Program\Stat\f_waterfall_806_CLL_WM_BTKI.sas 31MAY2022 10:08 33 Luxeptinib: Waterfall Plot of Best Response Shows Encouraging Antitumor Activity Trend in Heavily Pretreated Patients with B - Cell Malignancies Best Response in Evaluable Patients Includes all patients who had at least one imaging for tumor measurements or IgM measurement (WM patient) since starting trea tme nt (n=16) Encouraging Trends: • Observing greater antitumor activity with higher dose levels, higher plasma concentrations, and longer time on study drug • Observing antitumor activity across diverse B - cell cancers Data cut - off: 31May2022
Luxeptinib Case Study: Significant Tumor Reduction (47% ) with Accompanying Complete Metabolic Response (CMR) in Patient with Refractory Follicular Lymphoma Follicular Lymphoma Complete Metabolic Response and Tumor Reduction Patient 72 - year - old Male with Follicular Lymphoma : Received 450mg BID Luxeptinib Prior Therapies Failed • revlimid+obinutuzumab , obinutuzumab , ublituximab , umbralisib Response at C5D1 • 47% tumor reduction by SPD (PR requires 50%); 29% Reduction by SLD (PR requires 30%) • CMR (Complete Metabolic Response) by Cycle 3 34 Screening Cycle 5 Day 1
Luxeptinib Case Study: Dose - dependent Anti - tumor Activity in a Patient with Refractory Follicular Lymphoma Follicular Lymphoma Significant Tumor Reduction and Well Tolerated Demographics 60 - year - old female Diagnosis at Study Entry Grade 1 FL Prior Therapies Failed • bendamustine + obinutuzumab • rituximab Dose 450mg BID 7 cycles, followed by 600mg BID 8 cycles Response Tumor growth continued, though slowed, while on 450mg BID through 7 cycles: • SPD increased 28.2%, 10.7% and 8.7% at C3D1, C5D1 and C7D1, respectively, when compared with previous FDG PET - CT scan 43% tumor reduction from peak (12% below baseline) upon dose escalation to 600mg BID: • Following dose escalation to 600mg in cycle 8, lesion growth arrested, followed by continuous reduction to below baseline • By C15D1, primary lesions shrank by 42.5% and 11.3% when compared with highest measurement (C7D1) and baseline (screening), respectively 35
Luxeptinib : Ongoing Phase 1a/b Study in R/R AML and HR MDS 36 Cohort 4 900 mg Q12H Ongoing Cohort 3 750 mg Q12H Completed Cohort 2 600 mg Q12H Completed Cohort 1 450 mg Q12H Completed Dose Escalation Phase • Oral capsules administered twice daily on a 28 - day cycle • Planned expansion cohorts after dose escalation • Additional patients may be enrolled ( back filling ) at dose levels previously declared safe • Intra - patient dose escalation is allowed if higher dose is safe in 3 or more patients Objectives Ongoing Phase 1 a/b, open - label, single arm, multicenter, 3+3 dose - escalation clinical study (NCT04477291). Primary objectives: • Assess safety and tolerability of luxeptinib (CG - 806) • Determine maximum tolerated dose (MTD) and / or recommended Phase 2 dose (RP2D) Key secondary objectives: • Assess PK profile and PD activity • Obtain preliminary evidence of antitumor activity PATIENT POPULATION Relapsed or refractory AML and higher - risk MDS who failed or are ineligible for / intolerant of intensive chemotherapy or transplantation • Patients failed by FLT3i, IDHi , venetoclax, chemotherapy • Patients unfit for intensive therapy or failed by HSCT G3 capsules introduced into ongoing cohort 4
Luxeptinib: Swimmers’ Plot of Heavily Pretreated Patients with R/R AML Treated with Luxeptinib 37 1 29 57 85 113 141 169 197 225 253 281 309 337 365 393 421 Days on Study Treatment Safety Follow-up On Study Treatment 900 mg 750 mg 600 mg 450 mg 450 450 450 450 450 450 600 600 600 600 750 750 750 750 750 750 750 750 750 900 900 900 900 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 21* 22* 23* 17 18 19 20* De novo De novo De novo Secondary De novo De novo De novo De novo Secondary De novo De novo Secondary t-AML De novo Secondary De novo De novo Secondary De novo Secondary De novo De novo De novo WT ITD ITD ITD ITD WT ITD WT WT ITD ITD ITD TKD ITD ITD ITD WT WT Unk WT WT ITD WT (mg) Dose Pt# Type AML Status FLT3 DDI Data Cut - off Date of 31 May 2022
Luxeptinib Case Study : Durable MRD - negative CR in FLT3+ Patient with high plasma exposure levels FLT3 - ITD+ R/R AML CR / MRD - Demographics 46 - year - old male Diagnosis at Study Entry FLT3 - ITD+, relapsed de novo AML with myeloid sarcoma (bone marrow & extra medullary disease) Prior Therapies • Heavily pretreated, failed by chemotherapy / prior - FLT3i / 2 allogeneic transplants • Induction chemotherapy, followed by salvage chemotherapy + FLT3i followed by HSC Transplant #1 • Following HSC relapse, treated with decitabine + venetoclax + FLT3i followed by 2 nd HSC Transplant • Following 2 nd HSC relapse & increased BM blast received focal radiation to perispinal mass Dose 450mg BID luxeptinib Response • Abnormal bone marrow blast reduced to 0.6% on C2D1 and remained undetectable thereafter • Patient experienced no myelosuppression with blood counts sustained at normal levels • Highly sensitive flow cytometry detect ed no abnormal blasts in bone marrow at C4D1 and C5D3 MRD - CR: FLT3+ patient continues on study in Cycle 13 38
Luxeptinib Ongoing Activities • Ongoing Clinical Development in Two Separate Trials and Patient Populations • Phase 1 trial in patients with R/R B - cell leukemias|lymphomas • Phase 1 trial in patients with R/R AML • Critical Step for Lux Program is the Transition to a Novel and Improved Formulation (G3) • Goals to achieve greater plasma exposures with administration of less drug substance and fewer number of pills • Lux G3 Formulation is Being Tested Relative to the Original Formulation in Both Phase 1 trials • Patients Enrolling Well, Allowing us to Test a Single Dose of Lux G3 at Multiple Dose Levels • Already dosed G3 formulation at 50 mg, 100 mg and 200 mg • Following a Single Dose of Lux G3, Patients Continue on Study Using the Original Formulation • We plan to provide the antitumor data in a corporate slide deck later and then more rigorously during ASH • Presenting PK Data with the Lux G3 Formulation • Four patients dosed with 50 mg, 3 patients dosed with 100 mg, and 3 patients dosed with 200 mg (data from 1 available) 39
Luxeptinib: Single Dose G3 Formulation with 50 mg, 100mg, or 200 mg Dosages 40 • Patients participating in G3 study are derived from: • Ph 1 R/R B - cell cancers • Ph 1 R/R AML • 72 hr following single dose of G3: • Some received 750mg G1 • Some received 900mg G1 G3 Dose G1 Dose No. Patients 50 mg 750 mg 1 50 mg 900 mg 3 100 mg 750 mg 2 100 mg 900 mg 1 200 mg 900 mg 3 Encouraging PK data from Single Dose G3 Analysis
0.001 0.01 0.1 1 10 0 4 8 12 16 20 24 Hours Post Dosing Plasma Concentration ( uM ) PK Comparison of 50mg G3 to 900mg G1 Luxeptinib in AML Patient G3 50mg G1 900mg G1 150mg 0.001 0.01 0.1 1 10 0 24 48 72 96 PK Comparison of 50mg G3 to 900mg G1 Luxeptinib in AML Patient Hours Post Dosing Plasma Concentration ( μ M) Luxeptinib: First Patient Dosed with G3 Formulation PK Comparison of G3 50mg Single Dose to G1 900mg Single Dose (18X) 41 CONFIDENTIAL G1 150mg Separate Study Lowest G1 Dose Tested 200x exposure/mg at 2hr G3 50mg Single Dose PK (72hr), followed by G1 900mg Single Dose PK in Same Patient G3 50 mg dosing G1 900 mg dosing
42 Targets Kinases Important in Lymphoid and Myeloid Cancers • Inhibits BTK , FLT3 , CSF1R, PDGFR α , TRK, AURK, others • Generally w ell - tolerated – currently dosing at 900mg BID with original formulation • Delivered antitumor activity in diverse B - cell cancers • Delivered MRD - CR in relapsed AML patient with high exposure Findings to Date Identify Needs for Future Development • Clinical activity and tolerability justify further dose exploration • Doses of 450 - 750mg with original formulation provided incremental exposure increases • Identified need for consistent and higher exposure levels in AML & B - cell cancer patients Luxeptinib : Oral Lymphoid and Myeloid Kinome Inhibitor Next Steps for Luxeptinib in 2022 • Continue exploring improved G3 formulation to increasing exposure and to lower pill burden and drug substance manufacture • G3 early data are encouraging • Higher dosages may be evaluated • PK modeling of continuous dosing • Plan continuous dosing with G3 if the data from single dose and modeling are supportive
Aptose Biosciences (NASDAQ: APTO) Clinical Stage Oncology Company ᄫ Focused on Precision Medicines D eveloping highly differentiated oral kinase inhibitors for hematologic malignancies Experienced leadership with deep expertise in kinase inhibitors & orphan diseases Planned value - driving clinical updates through 2022 and cash runway through 2023 LUXEPTINIB (CG - 806) Dual Lymphoid and Myeloid Kinome Inhibitor High value targets in B - cell cancers, AML, and inflammation : BTK, FLT3, LCK, LYN, Others Ongoing parallel dose escalations in patients with B - cell l ymphomas /CLL and AML/MDS Clinically active: anti - tumor activity in high - bar clinical setting of R/R patients → Encouraging data with G3 formulation to reduce drug substance and increase plasma exposure HM43239 O ral Myeloid Kinome Inhibitor ᄫ Clinically Validated for R/R AML Patients Targets high value kinases operative broadly in AML patients : FLT3 WT/MUT , SYK, JAK1/2, cKIT MUT CRs in diverse R/R AML patients: FLT3 ITD/TKD/WT , NPM1 MUT , TP53 MUT , N/K - RAS MUT , MLL, RUNX1, IDH MUT Orphan Drug Designation for AML and Fast Track Designation for R/R AML patients with FLT3 MUT → Now Transitioning to Expansion Trials planned 2H2022 : Dose s and patient populations selected 43
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