Shattuck Labs : EHA 2024 Data Presentation

Interim Safety and Efficacy Update for SL-172154 with Azacitidine in Frontline HR- MDS and TP53m AML

NASDAQ: STTK

June 14, 2024

Forward-Looking Statements

This presentation contains "forward-looking statements" within the meaning of the federal securities laws, which statements are subject to substantial risks and uncertainties and are based on our estimates and assumptions. All statements, other than statements of historical facts included in this presentation, are forward-looking statements, including statements concerning our plans, objectives, goals, strategies, future events, plans or intentions relating to products and markets, the safety, efficacy and clinical benefits of our product candidates, alone or in combination with other agents; including the potential clinical benefits of SL-172154; the anticipated timing and design of our planned and ongoing preclinical studies and clinical trials, including initiation of additional cohorts, the anticipated timing for data, the association of preclinical data with potential clinical benefit, the timing of anticipated milestones, plans and objectives of management for future operations and future results of anticipated product development efforts, the timing of expected announcements, potential addressable market size and our liquidity and capital resources and business trends. In some cases, you can identify forward-looking statements by terms such as "may," "might," "will," "objective," "intend," "should," "could," "can," "would," "expect," "believe," "design," "estimate," "predict," "potential," "plan," or the negative of these terms, and similar expressions intended to identify forward-looking statements. These statements involve known and unknown risks, uncertainties and other factors that could cause our actual results to differ materially from the forward-looking statements expressed or implied in this presentation, in addition to those risks and uncertainties, such as the effects from the COVID-19 pandemic on our clinical trial activities, the uncertainties inherent in the clinical drug development process, such as the regulatory approval process, the timing of our regulatory filings, the potential for substantial delays, and the risk that earlier study results may not be predictive of future study results, manufacturing risks, and competition from other therapies or products, described in "Risk Factors" and "Management's Discussion and Analysis of Financial Condition and Results of Operations" in our Annual Report on Form 10-K (File No. 001-39593) for the fiscal year ended December 31, 2023 and elsewhere in such filing and in our other periodic reports and subsequent disclosure documents filed with the U.S. Securities and Exchange Commission.

We cannot assure you that we will realize the results, benefits or developments that we expect or anticipate or, even if substantially realized, that they will result in the consequences or affect us or our business in the way expected. Forward-looking statements are not historical facts, and reflect our current views with respect to future events. Given the significant uncertainties, you should evaluate all forward-looking statements made in this presentation in the context of these risks and uncertainties and not place undue reliance on these forward- looking statements as predictions of future events. All forward-looking statements in this presentation apply only as of the date made and are expressly qualified in their entirety by the cautionary statements included in this presentation. We have no intention to publicly update or revise any forward-looking statements to reflect subsequent events or circumstances, except as required by law.

We obtained the data used throughout this presentation from our own internal estimates and research, as well as from research, surveys and studies conducted by third parties. Internal estimates are derived from publicly available information released and our own internal research and experience, and are based on assumptions made by us based on such data and our knowledge, which we believe to be reasonable. In addition, while we believe the data included in this presentation is reliable and based on reasonable assumptions, we have not independently verified any third-party information, and all such data involve risks and uncertainties and are subject to change based on various factors.

This presentation concerns a discussion of investigational drugs that are under preclinical and/or clinical investigation and which have not yet been approved for marketing by the U.S. Food and Drug Administration. They are currently limited by Federal law to investigational use, and no representations are made as to their safety or effectiveness for the purposes for which they are being investigated.

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Shattuck Conference Call and Webcast Agenda

	Introduction	Taylor Schreiber, M.D., Ph.D.	Chief Executive Officer
			Professor and Director of the
	Interim Safety and Efficacy Update in	Naval Daver, M.D.	Leukemia Research Alliance
	Frontline HR-MDS and TP53m AML	Program at the
		MD Anderson Cancer Center
		Taylor Schreiber, M.D., Ph.D.	Chief Executive Officer
	Key Takeaways and Closing Remarks

Q&A	Shattuck Management

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SL-172154:First-In-Class CD47 Inhibitor + CD40 Agonist

SL-172154

(SIRPα-Fc-CD40L)

High Affinity & Avidity CD47 Binding

Designed to inhibit the CD47/SIRPα interaction to block the

macrophage "don't eat me" signal to potentiate phagocytosis

Inert Fc Domain

Designed to eliminate Fc-mediated effector function and associated cytopenias

Activation of CD40 Pathway

Designed to enhance antigen cross-presentation and T cell activation, potentially bridging innate and adaptive immunity

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Rationally Designed to Maximize the Potential Benefits of CD47 Blockade

Pursuing Clinical Differentiation Across SL-172154 Program

SL-172154

(SIRPα-Fc-CD40L)

High Affinity & Avidity CD47 Binding

Designed to inhibit the CD47/SIRPα interaction to block the

macrophage "don't eat me" signal to potentiate phagocytosis

Inert Fc Domain

Designed to eliminate Fc-mediated effector function and associated cytopenias

Activation of CD40 Pathway

Designed to enhance antigen cross-presentation and T cell activation, potentially bridging innate and adaptive immunity

Other CD47-targeted agents1

Efforts to inhibit CD47 have faced challenges. Several programs have shown mixed efficacy and toxicity

Competent Fc programs have observed safety related issues, including anemia and cytopenias

No dual activation of immune cells

by CD40 engagement

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1. Comparisons across trials have inherent limitations, including due to differences in subject characteristics, study sites, trial designs and other factors. No head-to-head trials have been conducted and caution should be exercised when comparing data from unrelated studies.

CD47/SIRPα Axis Engages Macrophages and

CD40 Activation Primes APCs for Anti-Tumor Response

SIRP

S

"don't eat"

Antigen

Presenting	Cancer
Cell
Cells/
Macrophage

"eat"

S

1	CD47 blockade disables the "don't eat me"
	checkpoint on antigen presenting cells (APC)

eat me signals

	m b or	2	Chemotherapies, ADCs, or targeted mAbs provide the
			"eat me" signal on tumor cells to promote phagocytosis
F	Receptor

3	CD40 activation enhances antigen cross-presentation by APC to
	CD8 T cells, potentially bridging innate and adaptive immunity

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Emerging Clinical Results May Be Attributable to CD40 Agonism

Frontline

HR-MDS

Platinum Resistant Ovarian Cancer

SIRPα-Fc Agents

Evorpacept + azacitidine1

15%

Complete response rate

Maplirpacept + liposomal doxorubicin2

0%

Overall response rate

SIRPα-Fc-CD40L(SL-172154)

SL-172154 + azacitidine

42%

Complete response rate

SL-172154 + liposomal doxorubicin

19%

Overall response rate

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1. ALX Oncology ASPEN-02 trial results presented at AACR 2024 Annual Meeting (Abstract ID CT060)
2. Daron G. Street et al., A phase I/II study of maplirpacept in combination with pegylated liposomal doxorubicin (PLD) in patients with platinum-resistant ovarian cancer (OC): Phase 1 results. JCO 42, e17546-e17546(2024). DOI:10.1200/JCO.2024.42.16_suppl.e17546
   Note: Comparisons across trials have inherent limitations, including due to differences in subject characteristics, study sites, trial designs and other factors. No head-to-head trials have been conducted and caution should be exercised when comparing data from unrelated studies.
   This slide shows interim, preliminary data available to Shattuck as of the April 23, 2024 data cutoff. The data are subject to change as more patient data become available and are subject to audit and verification procedures that could result in material changes in the final data. Note: Response Evaluation Per IWG 2006 Criteria

Additional Data from Phase 1B Dose-Expansion Cohorts in Patients with Previously Untreated TP53m AML and HR-MDS

Dr. Naval Daver, M.D.

Professor and Director of the Leukemia Research Alliance Program in the Department of Leukemia at MD Anderson Cancer Center

Ongoing Phase 1A/B Trial Design in AML/HR-MDS

Currently in Combination with Azacitidine

Phase 1A	Phase 1B
Dose Escalation	Dose Expansion

Dose Escalation Complete	3 mg/kg selected
Primarily R/R AML and HR-MDS	as dose for SL-172154

Frontline AML with TP53m

SL-172154 + azacitidine

Completed Enrollment in Q1'24

Frontline Higher-Risk MDS

SL-172154 + azacitidine

Completed Enrollment in Q4'23

SL-172154 (IV): D2, D9, D16 and D23 for first 2 cycles (q28d cycle), then D2 and D16 for cycle 3 and later

Azacitidine: 75 mg/m2 IV or SQ once daily (D1-D7) or 5-2-2 Schedule

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Demographics and Disease Characteristics in Previously Untreated TP53m AML Patients

Previously Untreated TP53m AML

TP53 mutation/deletion	21	(100%)
Complex karyotype	19 (91%)
Secondary AML	14 (67%)
Pure erythroid leukemia	3	(14%)
Bone marrow blast at baseline
<30%	10 (48%)
30% to <50%	6	(29%)
≥50%	5	(24%)
RBC transfusion dependent	13 (62%)
Platelet transfusion dependent	4	(19%)

• Median age was 74
• 71% were male and 29% female
• Poor prognosis patient population
• • 91% have complex karyotype
  • 67% have secondary leukemia
• Significant unmet need for effective therapies in this patient population

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omplex karyotype is defined as ≥3 cytogenetic abnormalities. Transfusion dependent is defined as M :≥ transfusion within weeks prior to 1st dose of study treatment.

This slide shows interim, preliminary data available to Shattuck as of the April 23, 2024 data cutoff. The data are subject to change as more patient data become available and are subject to audit and verification procedures that could result in material changes in the final data. Note: Response Evaluation Per ELN 2017