Tuspetinib to Treat Newly Diagnosed AML

Corporate Presentation

April 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 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 timeline, 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.

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

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Tuspetinib Lead Clinical Asset

  • Developing TUS+VEN+HMA triplet as frontline therapy to treat newly diagnosed AML ׀ Begins Summer of 2024
  • Excellent safety profile ׀ Ideal for combination therapy
  • Potently targets SYK, FLT3, KITMUT, JAK1/2, RSK2 kinases

3TUS : Tuspetinib ; VEN : Venetoclax ; HMA : Hypomethylating agent

AML : Acute Myeloid Leukemia

The Problem Treating AML

  • Response rates too low and survival too short in frontline (1L) therapy
  • Progress treating 1L AML with VEN+HMA (SOC) but not curing

The Needs of AML Patients

  • Achieve longer survival and treat broader scope of subgroups in 1L
  • Add a 3rd agent to VEN+HMA SOC - Current inadequate

Tuspetinib Opportunity ׀ Addressing 1L Unmet Needs

  • 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 as a new SOC addresses 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

Tuspetinib Compensates for

Venetoclax Resistance

TUS

FLT3-ITD

KIT-MUT

JAK1/2 RAS/MAPK TP53-MUTMCL-1 ↑

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

TUS targets VEN resistance pathways

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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4

Greatest Need in AML Therapy Today

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

Annual Deaths 11,2003 | 5-yr Survival 30% in Adults1 | 5-yr Survival 9% for Age >651. | Avg age a diagnosis 68

  • Chemotherapy is not an option for most of the AML patient population
    • Chemotherapy may be beneficial for "Fit" younger patients without co-morbidities
    • Only 30-50% of AML patients are "Fit" for Chemo based therapies
    • Frontline therapies are making progress but leave substantial room for improvement
    • The CR rate of first-line treatment in young and middle-aged adults is 60%-80%,
    • Older patients >65 years of age have CR rates in first-line therapy of 40%-60% with high rates of relapse
  • Elderly populations have seen improved efficacy with venetoclax-containing doublet therapy
    • VEN/HMA: CR = 37%, CRc = 66%, median OS = 14.7 months
    • However, patients with adverse mutations in FLT3, NRAS, KRAS, and TP53 have inferior outcomes
  • Triplet combination studies have shown better efficacy, but increased toxicity requires dose reductions
    • Studies have shown upper ranges of response at CRc 90% and CR >70%
      • Combinations have been more toxic, requiring dose reductions of all agents
      • And the targeted agents do not have broad activity across AML genotypes
  • Safe and effective therapies to improve outcomes for AML patients of all genotypes represent an urgent need in AML

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

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AML Patient Journey | 1L Therapy High-Level Overview

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

5-year

Age5

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%

Newly

Patients "Fit"

Intensive

for High Dose

Chemotherapy

Chemotherapy

(7+3)

Therapeutic

Failure

HSCT

Maintenance

Therapeutic

Diagnosed

Complete Remission

Therapy

Failure

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

Maintenance

Therapeutic

Therapy

Failure

Therapeutic

Failure

  1. NIH; Yale Medicine; American Cancer Society; NIH; Healthline

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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

Tuspetinib Frontline Triplet Opportunities

TUS + VEN + HMA

Patients "Fit"

Intensive

FLT3 MUT

׀ Increase CR rates and survival with a better

for High Dose

Chemotherapy

safety profile

Chemotherapy

(7+3)

FLT3 WT

׀ Increase CR rates and 1-yr survival better

Need a superior 1L therapy that treats

than HMA+VEN

more patients, increases survival, and

avoids 1L therapeutic failures

Treats a broad scope of AML subtypes, including highly

Patients "Unfit"

Low Intensity

adverse TP53 MUT, NKRAS MUT

for High Dose

Therapy

Chemotherapy

(VEN + HMA)

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

VEN + HMA + Gilteritinib triplet has superior OS to VEN + HMA doublet in newly diagnosed FLT3+ AML patients

Current Problem

Gilteritinib-basedtriplet not active in FLT3-WildtypeAML (70% of patients) and toxicities require SOC dose reductions

TUS safety shows no signal of overlapping toxicities with VEN or HMA backbone agents

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

TUS Superior to Gilt

for 1L

TUS clinical efficacy is superior to 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 or AZA (HMA) safe and effective in animal models of human AML

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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 Dose Exploration

Demonstrate Single Agent Safety

Demonstrate Single Agent Efficacy

Tus + Ven Doublet Study in R/R AML

Characterize Safety of 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

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TUS+VEN+AZA TRIPLETPilot Study: Design, Patient Populations, Dose Selection, Goals

Patient Populations │ 20-36 Pts Total │ 50% FLT3-MUT │ <20% TP53+/CK

Dose Selection │ Explore 80, 120, 160mg Doses for Optimal Phase 2 Dose of TUS and Avoid SOC Dose Reductions

Trial Goals │ Safety, CR rate, MRD negativity and OS across AML subtypes (FLT3MUT/WT , TP53MUT, RASMUT)

Cycle 1 Treatment Plan:

TUS

TUS once daily

VEN

400 mg once daily

AZA

75mg/m2 once daily

Day 1

Day 7

TUS

TUS once daily

VEN

400 mg once daily

AZA

75mg/m2 once daily

Day 1

Day 7

Day 18 Day 21 BM Decision

BM blasts <5%

or aplastic

BM blasts ≥ 5%

Cycle 1 extended if needed to

allow for count recovery*

Day 28

Cycle 1 extended if needed to

allow for count recovery*

Day 28

VEN and TUS held if BM blasts <5% or aplastic, otherwise move to Cycle 2

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* GCSF permitted after D28 per protocol

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Aptose Biosciences Inc. published this content on 24 April 2024 and is solely responsible for the information contained therein. Distributed by Public, unedited and unaltered, on 24 April 2024 20:59:59 UTC.