Tuspetinib to Treat Newly Diagnosed AML

Corporate Presentation

May 2024

P R E C I S I O N O N C O L O G Y F O R T H E R A P I E S O F T O M O R R O W

Aptose Leadership Team: Multifaceted Expertise in Therapeutic Development

William G. Rice, PhD

Fletcher Payne

Rafael Bejar, MD, PhD

Chairman, President

Sr. VP, Chief Financial Officer

Sr. VP & Chief Medical Officer

& Chief Executive Officer

& Chief Business Officer

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Aptose Disclosure

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This presentation contains forward-lookingstatements, 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 timelines and milestones, the efficacy and toxicity of our product 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 securities laws.

Although the Company believes that the views reflected in these forward-looking statements are reasonable, such statements involve 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-looking 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 continue our operations, changing market conditions, the successful and timely completion of our clinical studies including delays, the demonstration of safety and efficacy of our drug 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 and pricing, 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 Company'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 purpose of assisting potential investors in understanding the Company's business and may not be appropriate for other purposes. The Company does not undertake to update 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. Investors

should read the Company's continuous disclosure documents available at www.sedarplus.comand EDGAR at www.sec.gov/edgar.shtml,especially the risk factors detailed therein.

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Tuspetinib Lead Clinical Asset

  • TUS+VEN+HMA triplet is being developed as frontline therapy to treat newly diagnosed AML
  • Frontline triplet clinical data expected 2H 2024
  • Potently targets SYK, FLT3, KITMUT, JAK1/2, RSK2 kinases

4TUS : Tuspetinib ; VEN : Venetoclax ; HMA : Hypomethylating agent

AML : Acute Myeloid Leukemia ; SOC : Standard of Care

Unmet Need for Superior Frontline (1L) Therapy in AML

  • Progress made with VEN+HMA (SOC) but unmet needs still exists
    • Response rates too low and survival too short in 1L therapy
    • Resistance to VEN compromises subsequent R/R therapies
  • A 3rd agent is needed to boost responses with VEN+HMA SOC
  • Current 3rd agents inadequate - those in development only address specific genetic subtypes and are limited by toxicities

Tuspetinib Opportunity ׀ Addressing 1L Unmet Needs

  • TUS is the ideal 3rd agent for addition to VEN+HMA
  • TUS has excellent safety in combination with VEN and HMA
  • TUS increases efficacy in combination with VEN and HMA
  • TUS has broad scope of activity across AML genetic subgroups

TUS+VEN+HMA … creating a new SOC addressing safety, scope, and survival needs of newly diagnosed AML patients

Tuspetinib Enhancing Venetoclax Efficacy in Frontline Therapy TUS and VEN mechanistically cooperate to prevent drug resistance

VEN BCL-2i resistance involves mutations in multiple pathways to evade BCL-2 blockade

TUS targets VEN resistance pathways

  • TUS suppresses SYK, KITMUT, FLT3, JAK/STAT, RAS/MAPK pro-survival signaling and indirectly suppresses MCL-1anti-apoptotic signaling

By shutting down escape pathways, TUS may re-sensitize prior- VEN failures to venetoclax

KIT

FLT3

SYK

JAK/STAT

TUS

PI3K/AKT

RAS/

MAPK

MCL-1

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Greatest Need in AML Therapy Today

"We are making progress but are not curing our patients1."

Annual new cases in U.S. ≈ 21,0002

|

Median age at diagnosis 682

Annual deaths in U.S. ≈ 11,2002

|

5-yr survival ≈ 30% in Adults2 | 5-yr Survival 9% for Age >652

Frontline therapies are making progress but leave substantial room for improvement

  • Younger "Fit" patients achieve >50% CR, but only 30-50% of patients are "Fit" and many relapse3
  • Older "Unfit" patients achieve improved efficacy with VEN+HMA doublet but many relapse
    • VEN+HMA(AZA): CR = 37%, CR/CRi = 66%, median OS = 14.7 months4
  • Patients with adverse FLT3, N/KRAS, and TP53 mutations correlated with poor response/outcomes

Current triplets can deliver better efficacy, but increased toxicity requires dose reductions

  • Studies have shown upper ranges of response at CRc >90%
  • Current 3rd agents with VEN+HMA have been more toxic, requiring dose reductions of all agents
  • Current 3rd agents with VEN+HMA do not deliver broad activity across AML genotypes

Urgent need for safer and more effective 1L triplet therapies to improve outcomes for AML patients of all genetic subtypes

1

Catherine E. Lai, MD, MPH, of the University of Pennsylvania

2 NIH; Yale Medicine; American Cancer Society; NIH; Healthline

3

Kantarjian, Blood Canc J 2021

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DiNardo, NEJM 2020; Pei, Cancer Discos 2020; DiNardo, Blood 2020; Maiti, Haematologica

CR : Complete Remission ; CRc : composite Complete Remission ; OS : Overall Survival

2021; Mannis, Leukemia Research 2023; Bewersforf, Leukemia Research 2022

5-year

Age2

survival

rate

Children < 14

65-70%

Ages 15 to 34

52%

Ages 35 to 54

37%

Ages 55 to 64

20%

Ages 65 to 74

9%

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AML Patient Journey | 1L Therapy High-Level Overview

Current Standard-of-Care (SOC) treatment options leading to therapeutic failure……

Newly

Patients "Fit"

Intensive

for High Dose

Chemotherapy

Chemotherapy

(7+3)

Therapeutic

Failure

HSCT

Maintenance Therapeutic

Diagnosed

Complete

TherapyFailure

AML

Palliative

Care

5-year survival <10% for age >701 ; Most survive <1 year

Patients "Unfit"

Low Intensity

for High Dose

Therapy

Chemotherapy

(VEN + HMA)

CR = 37%

CRc = 66%

mOS = 14.7 mos1

Remission

Maintenance Therapeutic

TherapyFailure

Therapeutic

Failure

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1 Pei, Cancer Discos 2020); DiNardo, Blood 2020); (Maiti et al., Haematologica 2021); (Mannis

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et al., Leukemia Research 2023); Bewersforf et al., Leukemia Research 2022; 122: 106942

AML Patient Journey | 1L Therapy High-Level Overview

Tuspetinib-containing triplet can become a new 1L SOC to increase survival

Newly

Diagnosed

AML

Tuspetinib Triplet Opportunity

TUS + VEN + HMA

Patients "Fit"

Intensive

for High Dose

Chemotherapy

Chemotherapy

(7+3)

Need a superior 1L therapy that treats

more patients, increases survival, is

safer, and avoids 1L therapeutic failures

Patients "Unfit"

Low Intensity

for High Dose

Therapy

Chemotherapy

(VEN + HMA)

Tuspetinib Frontline Triplet Opportunities

  • Potential to increase CR rates and survival of FLT3 MUT patients without the need to dose reduce SOC drugs
  • TUS is the only agent being developed in combination with VEN+HMA for FLT3 WT AML patients (70% of AML)
  • TUS is the only agent being developed in combination with VEN+HMA for high-risk AML subtypes with highly adverse TP53 and NKRAS mutations
  • TUS+VEN+HMA expected to be a safer therapy for
    "unfit" patients than other triplets

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New Paradigm in Frontline Therapy to Treat Newly Diagnosed AML

Deploying Triplet Combinations of Targeted Drugs | Building on VEN + HMA Backbone for 1L Therapy

Proof for Triplets : Addition of a 3rd Targeted Agent Boosts VEN+HMA Responses in 1L AML

Addition of gilteritinib (Gilt) FLT3i to VEN+HMA boosts CR rate 2.4X in newly diagnosed FLT3+ AML patients1

Problem: Current 3rd Agents for Triplets have Limitations

Gilt is not active in FLT3-Wildtype AML (70% of patients) and toxicities of Gilt with VEN+HMA require SOC dose reductions

Solution: TUS Fulfills Ideal Profile as

3rd Agent for 1L Triplet

TUS clean safety is ideal for addition to

VEN+HMA backbone

  • TUS shows no QTc prolongation, differentiation syndrome, muscle damage, or prolonged myelosuppression in remission
  • TUS is not expected to require dose reductions or interruptions to SOC drugs

TUS clinical efficacy broader than Gilt and

achieves CR in high-risk AML

  • TUS achieves clinical responses in patients who failed prior therapy with Gilt
  • TUS achieves clinical responses at lower and better-tolerated doses than Gilt
  • TUS achieves clinical responses in FLT3WT patients (70% of AML population), a population not addressable by Gilt FLT3i

TUS preclinical safety, antitumor, mechanistic findings superior to Gilt

  • TUS MOA targets VEN-resistance mechanisms and re-sensitizes cells to VEN
  • TUS suppresses more oncogenic signaling pathways than Gilt and at lower doses
  • TUS potent antitumor activity in animal models of human AML resistant to Gilt
  • TUS+VEN & TUS+HMA safe and effective in animal models of human AML

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1 Short et al. J Clin Oncol. 2024 Jan 26:JCO2301911. Epub ahead of print. PMID: 38277619.

FDA Requirements for TUS to Enter Frontline Therapy in Newly Diagnosed AML

Tuspetinib has Met the FDA Requirements to Perform the Triplet Pilot Study

What Does the FDA Want?

Aptose

Begin in R/R AML with TUS and TUS+VEN

Completed

TUS Single Agent Study in R/R AML

Thorough Single Agent Dose Exploration

Demonstrate Single Agent Responses

Demonstrate Single Agent Safety

Tus+Ven Doublet Study in R/R AML

Characterize Safety of TUS+VEN Doublet

Characterize PK of TUS and VEN in Doublet

Next Step: TUS+VEN+AZA Triplet Pilot Study

Initiate dosing and collect data from

Triplet Pilot Study in Newly Diagnosed AML Patients

Protocol implemented and clinical sites being prepared

  • Select optimal dose of TUS that allows for SOC dosing
  • Characterize safety and mitigate myelosuppression
  • Characterize activity in TP53MUT and N/KRASMUT
  • Characterize activity in FLT3MUT and FLT3UNMUT
  • Characterize PK of TUS and VEN in triplet
  • Determine CR, CRh, CRc, MRD rates
  • Characterize duration of dosing
  • Characterize mOS

Tuspetinib Achieved Orphan Drug Designation and Fast Track Status

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Aptose Biosciences Inc. published this content on 03 May 2024 and is solely responsible for the information contained therein. Distributed by Public, unedited and unaltered, on 03 May 2024 14:56:02 UTC.