APTE BIOS : Earnings Presentation

Tuspetinib clinical strategy as a triplet frontline therapy to treat newly diagnosed AML

Earnings Call Presentation

14 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

Tuspetinib

Aptose's Lead Clinical Asset

• TUS+VEN+HMA triplet is being developed as frontline therapy to treat newly diagnosed AML
• Bolting TUS on VEN+HMA Frontline Standard of Care
• Expect clinical data from our frontline triplet 2H 2024

AML Highly Aggressive Cancer of Blood and Bone Marrow Unmet Need for Superior Frontline (1L) Therapy in AML

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

Tuspetinib Opportunity ׀ Addressing 1L Unmet Needs

• TUS is a natural 3rd agent for addition to VEN and 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 targets known VEN resistance mechanisms to minimize resistance

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

• TUS : Tuspetinib ; VEN : Venetoclax ; HMA : Hypomethylating agent
  AML : Acute Myeloid Leukemia ; SOC : Standard of Care

TUS Targets Known VEN-Resistance Mechanisms and May Minimize Drug Resistance

Tuspetinib suppresses:

SYK, KITMUT, FLT3MUT/WT, JAK/STAT, RAS/MAPK oncogenic signaling directly and MCL-1anti-apoptotic signaling indirectly

KIT	FLT3
SYK	TUS
JAK/STAT
PI3K/AKT
RAS/
MAPK

MCL-1

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AML Patient Journey | 1L Therapy High-Level Overview

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

Newly

Diagnosed

AML

Palliative

Care

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

Patients "Fit"	Intensive
for High Dose	Chemotherapy
Chemotherapy	(7+3)

Patients "Unfit"	Low Intensity
for High Dose	Therapy
Chemotherapy	(VEN + HMA)

CR = 37%

CRc = 66%

mOS = 14.7 mos1

Therapeutic

Failure

	HSCT	Maintenance	Therapeutic
Complete	Therapy	Failure
Remission	Maintenance	Therapeutic
	Therapy	Failure
Therapeutic
Failure

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• Pei, Cancer Discos 2020); DiNardo, Blood 2020); (Maiti et al., Haematologica 2021); (Mannis et al., Leukemia Research 2023); Bewersforf et al., Leukemia Research 2022; 122: 106942

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TUS+VEN+HMA May Increase Survival in High-risk Frontline (1L) Newly Diagnosed AML Patients with Adverse Mutations

• VEN+AZA combo delivers less benefit in "high-risk AML" with FLT3ITD, RASMUT, and TP53MUT
• Tuspetinib retains activity in high-risk AML with the adverse FLT3, RAS and TP53 mutations
• Tuspetinib added to VEN+AZA (HMA) may uniquely benefit the most challenging 1L populations

Frontline AML patients receiving VEN+AZA separate into three efficacy subgroups by OS benefit

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Dohner et al. ASH 2022

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

6	4 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

Age2		5-year
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

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 MUTpatients without the need to dose reduce SOC drugs
• TUS is the only agent being developed in combination with VEN+HMA for FLT3 WTAML patients (70% of AML)
• TUS is the only agent being developed in combination with VEN+HMA for high-risk AML subtypes with highly adverse TP53and N/KRASmutations
• 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	TUS clinical efficacy broader than Gilt and	TUS preclinical safety, antitumor,
VEN+HMA backbone	achieves CR in high-risk AML	mechanistic findings superior to Gilt

• 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 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 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.

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

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

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

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

Cycle 1 Treatment Plan:

Day 18	Day 21
BM	Decision	Cycle 1 extended if needed to
		allow for count recovery*

TUS		TUS once daily
VEN		400 mg once daily
AZA	75mg/m2 once daily	BM blasts <5%	Day 28
	Day 1	Day 7	or aplastic

Cycle 1 extended if needed to

allow for count recovery*

TUS		TUS once daily
VEN		400 mg once daily
AZA	75mg/m2 once daily	BM blasts ≥ 5%	Day 28
	Day 1	Day 7		VEN and TUS held if BM blasts <5%
				or aplastic, otherwise move to Cycle 2

10	* GCSF permitted after D28 per protocol
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