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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.

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Oral Presentation Delivered by Naval Daver, MD To the 65th ASH Annual Meeting & Exposition Saturday 09Dec2023

Tuspetinib Oral Myeloid Kinase Inhibitor Safety and

Efficacy As Monotherapy and Combined with Venetoclax in Phase 1/2 Trial of Patients with Relapsed or Refractory (R/R) Acute Myeloid Leukemia (AML)

Naval Daver1, Kyoo-Hyun Lee2, Yunsuk Choi2, Brian Jonas3, Martha Arellano4, Justin M Watts5, Pau Montesinos6, Uma Borate7, Paul B. Koller8, Chul-Won Jung9, Sang Kyun Sohn10, Pankit Vachhani11, Amir T. Fathi12, Sung-Soo Yoon13, Jeong-Ok Lee14, Ho-Jin Shin15, Gabriel Mannis16, Nikolai A.

Podoltsev17, Tan Shuhying18, Harry P. Erba19, Eric Tam20, Mar Tormo Diaz21, Jia Hu22, Ranjeet Kumar Sinha22, Nawazish Khan22, William Rice22, Rafael Bejar22

  1. The University of Texas MD Anderson Cancer Center Houston, TX,2Asan Medical Center, Seoul, SK, 3UC Davis Comprehensive Cancer Center, Davis, CA, 4Emory University, Atlanta, GA, 5University of Miami, FL, 6Hospital Universitari i Politècnic La Fe, Valencia, ESP, 7The James Cancer Hospital and Solove Research Institute, The Ohio State University, OH, 8Department of Hematology/HCT, City of Hope, Duarte,
    CA, 9Samsung Medical Center, Seoul, SK, 10Kyungpook National University Hospital Daegu, SK, 11University of Alabama, AL, 12Massachusetts General Hospital Boston, MA, 13Seoul National University Hospital, Seoul, SK, 14 Seoul National University Bundang Hospital, Seongnam, SK, 15Pusan National University Hospital, Busan, SK, 16 Stanford Cancer Center, Stanford, Palo Alto, 17 Yale School of Medicine, New Haven, CT, 18 St. Vincent's Hospital, Melbourne, AUS, 19Duke Cancer Center, Durham, NC, 20 USC Norris Comprehensive Cancer Center, Los Angeles, CA , 21Hospital Clínico Universitario, Valencia, ESP
  1. Aptose Biosciences Inc, San Diego, CA

Investment Highlights

Precision oncology company developing oral targeted agents to treat hematologic malignancies Tuspetinib (TUS) lead agent │Once daily oral kinase inhibitor for R/R acute myeloid leukemia (R/R AML)

  • Highly active as a single agent with an excellent safety record
  • Targets FLT3WT/MUT, SYK, KITMUT, JAK1/2, RSK2, TAK1-TAB1 kinases and suppresses MCL-1 expression
  • CR/CRh=36% All-comers │ CR/CRh=50% FLT3MUT │ CR/CRh=25% FLT3WT at the RP2D 80mg in VEN-naïve R/R AML

AML care shifted to Venetoclax(VEN) based combinations Emergenceof difficult-to-treatPrior-VEN failure population

  • Prior-Venfailure R/R AML patients have dismal response to salvage therapy: CR/CRh = 4-15% │ mOS = 2.8 months
  • Any new drug needs to combine well with VEN and treat Prior-VEN failure AML patients

Opportunities │ Tuspetinib is ideal for combination therapy with VEN-containing regimens and treating Prior-VEN failures

‒ TUS directly targets VEN resistance mechanisms │ Re-sensitizes VEN failures to VEN │ TUS/VEN successfully treats these VEN failures

TUS/VEN doublet planned for registrational trial in R/R Prior-VEN AML → Estimated $400 million market1 TUS/VEN/AZA triplet planned for pilot study in 1L Newly Diagnosed AML → Estimated $1 billion market1 Multiple value-creating milestones ahead

  • TUS/VEN further data on duration of response in R/R AML planned: 1Q & 2Q 2024
  • TUS/VEN/HMA planned initiation of pilot study in 1L AML: 1H 2024
  • Extension into HR-MDS and CMML planned

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3

1 Companycommercial forecast estimates

Tuspetinib Directly and Indirectly Targets Venetoclax Escape Mechanisms

Tuspetinib targets pathways involved

in resistance to Venetoclax

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

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

  • Strong evidence for combination therapy with tuspetinib and venetoclax
  • ESH Poster: Tuspetinib oral myeloid kinase inhibitor creates synthetic lethal vulnerability to venetoclax

KITMUT

FLT3MUT

SYK

JAKMUT/STAT TUS

PI3K/AKT

RASMUT/

MAPK

MCL-1

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4

C O N F I D E N T I A L

TUS/VENMay be Ideal Doublet Therapy in R/R Prior-VEN Failure AML

R/R AML Setting:AML care shifted toward Venetoclax (VEN) containing combination regimens and a new population of difficult-to-treat VEN failures is emerging

After failing venetoclax, AML is highly refractory to salvage

therapy(1,2,3,4)

  • Prior-VENfailures have "dismal" response rates to salvage therapy
  • Resistance involves alterations in multiple pathways (FLT3, NRAS, KIT, TP53, JAK1/STAT5, MCL-1)

Need Improved Therapy for R/R Prior-VEN Failures TUS/VEN combination is safe & active in Prior-VEN Potential first-to-market in R/R Prior-VEN setting

1Estimated $400 Mn opportunity forecast to treat the majority of R/R AML patients

66%

15%

4%

6%

1L CR Rate

Salvage 2L CR

Salvage 2L

Salvage 3L

Targeted CR

Targeted CR

1 Pei, Cancer Discos 2020); 2 DiNardo, Blood 2020); 3 (Maiti et al., Haematologica 2021); 4 (Mannis et al., Leukemia Research 2023); 5 Datamonitor Healthcare AML forecast July 2023; Also, Bewersforf et al., Leukemia Research 2022; 122: 106942.

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5

1 Companycommercial forecast estimates

TUS/VEN/HMAMay be Ideal Triplet Therapy in 1L Newly Diagnosed AML

1L Newly Diagnosed Setting:Venetoclax (VEN/HMA) in "Unfit"

patients dramatically increased response rates (CRc = 66%) and mOS (14.7 mos)

Problem: Need Improved 1L Therapy

  • 1L chemo and VEN/HMA not universally curative
  • VEN containing regimens are highly successful and will further revolutionize 1L therapy
  • Proof of Concept: Gilt/VEN/HMA triplet delivered high response rates, but Gilt limited to FLT3+ population (~30%) and limited by AEs

Need Improved 1L Triplet Therapy

TUS/VEN/HMA Triplet may expand treatable 1L populations (improved safety; fit and unfit ; FLT3 agnostic)

1Estimated $1Bn opportunity forecasted in front-line AML

66%

15%

4%

6%

1L CR Rate

Salvage 2L CR

Salvage 2L

Salvage 3L

Targeted CR

Targeted CR

1 Pei, Cancer Discos 2020); 2 DiNardo, Blood 2020); 3 (Maiti et al., Haematologica 2021); 4 (Mannis et al., Leukemia Research 2023); 5 Datamonitor Healthcare AML forecast July 2023; Also, Bewersforf et al., Leukemia Research 2022; 122: 106942.

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6

1 Companycommercial forecast estimates

Clinical Path to Support Clinical Development and Registrational Plans

Dose Escalation Ph 1/2

EOP1 Meeting

Trial in R/R AML

with FDA

Demonstrated

Successful meeting

tuspetinib single

and outcomes

agent activity

RP2D = 80mg once

Favorable safety and daily tolerability

All approval paths remain available

APTIVATE Expansion Trial in R/R AML

  • Tuspetinib or
    TUS/VEN
  • TUS/VEN favorable safety profile and is highly active, including prior-VEN failure difficult-to- treat subgroup

TUS/VEN Differentiation from Other Therapies

  • TUS/VEN impressive response rate in R/R prior-VEN AML
  • ~80% R/R prior-VEN patients entering APTIVATE trial
  • May enable accelerated approval development path

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Tuspetinib Single Agent Phase 1/2 Clinical Study

Tuspetinib Single Agent Phase 1/2 Study in R/R AML

  • TUS is dosed orally once daily in 28-day cycles without interruption
  • Safety and efficacy analyses include all dosed patients1
  • CRc = CR + CRh +CRp + CRi (incl MLFS)
  • Extensive dose exploration │ 91 patients dosed
  • Proportion of Prior-VEN patients increased over time, resulting in lower response rates at 120mg & 160mg
  • Therapeutic window 80 mg - 160 mg
  • CRs with no DLTs
  • CRs in patients with highly adverse genetics
  • RP2D = 80 mg once daily

Dose Escalation + Exploration + Expansion

Total VEN- Prior-

Naïve

VEN

n=

n=

n=

Cohort 1: 20 mg QD

2

1

1

Cohort 2: 40 mg QD

17

8

9

Cohort 3: 80 mg QD

20

14

6

Cohort 4: 120 mg QD

32

6

26

Cohort 5: 160 mg QD

16

8

8

Cohort 6: 200 mg QD

4

1

3

71% Prior-

VEN

9

1Data cut Oct 23, 2023

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Tuspetinib Single Agent Patient Baseline Characteristics

Highly treatment experienced and representative of current R/R AML patient population

Patient Characteristics (n=91)

FLT3MUT

FLT3WT

Patient number n (%)1

34

56

Population included FLT3WT & FLT3MUT

Median Age Years (Range)

60

(21-84)

65.5 (18-83)

Older: Median age > 60 years

Female n (%)

14

(41.2%)

24 (42.9%)

Lines prior therapy Mean (Range)

3.3 (1-11)

2.4 (1-6)

Prior-VEN represented > 50% of patients

Percentage increased as trial proceeded

Prior-VEN

19

(55.9%)

33 (58.9%)

Higher dose levels had higher percentages of

Prior-VEN patients

Prior FLT3 Inhibitor

17

(50.0%)

3 (5.4%)

Over 50% failed Prior-FLT3i

Prior Cytotoxic chemotherapy

26

(76.5%)

36 (64.3%)

Prior HMAs

22 (64.7%)

37 (66.1%)

Over 1/3 failed Prior-transplant

Prior HSCT

14

(41.2%)

19 (33.9%)

1 One patient had an indeterminant status for FLT3

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Aptose Biosciences Inc. published this content on 26 December 2023 and is solely responsible for the information contained therein. Distributed by Public, unedited and unaltered, on 26 December 2023 20:45:43 UTC.