Acurx Pharmaceuticals : ID Week Presentation by Dr. Michael Silverman and Dr. Kevin Garey Ibezapolstat October 2023

First of a New Class of Antibiotics (pol IIIC Inhibitors)

Targeting CDC/FDA/WHO Priority Pathogens

Preparing for the Next Pandemic: Antimicrobial Resistance in

Gram-positive Bacterial Infections

Presenter: Acurx Medical Director

Michael H. Silverman, MD, FACP*

Principal Investigator for Microbiome Aspects of Clinical Trial Program:

Kevin Garey, PharmD, MS

Professor & Chair, University of Houston College of Pharmacy

IDWeek, October 12, 2023

New Antimicrobials in the Pipeline

Robert J. DeLuccia, Executive Chairman

* Dr. Silverman is an independent consultant to Acurx; No disclosures

Disclosure	Acurx

Forward-Looking Statements

This presentation contains forward-looking statements as defined in the Private Securities Litigation Reform Act of 1995 regarding, among other things, development plans, regulatory activities, anticipated milestones, product candidate benefits, competitive position, business strategies, objectives of management, potential growth opportunities, potential market size, possible or assumed future results of operations, projected costs and use of proceeds. In some cases, forward-looking statements can be identified by terms such as "may," "will," "should," "expect," "plan," "aim," "anticipate," "could," "intent," "target," "project," "contemplate," "believe," "estimate," "predict," "potential" or "continue" or the negative of these terms or other similar expressions. All statements other than statements of historical facts contained in this presentation are forward-looking statements. Acurx Pharmaceuticals, Inc. (the " Company") may not actually achieve the plans, intentions or expectations disclosed in these forward-looking statements. Actual results or events could differ materially from the plans, intentions and expectations disclosed in these forward-looking statements as a result of various factors, including: uncertainties inherent in the initiation and completion of preclinical studies and clinical trials and clinical development of the Company's product candidates, including adverse results in our clinical development processes; whether results from one clinical trial will be predictive of the results of future trials and whether preliminary data from our clinical trials will be predictive of final results from such trials; decisions made by the U.S. Food and Drug Administration and other regulatory authorities with respect to the development and commercialization of our products; availability of funding sufficient for the Company's foreseeable and unforeseeable operating expenses and capital expenditure requirements; our ability to obtain, maintain and enforce intellectual property and other proprietary rights for our product candidates; our ability to implement our strategic plans; and other factors discussed in the "Risk Factors" section of the Company's filings with the Securities and Exchange Commission ("SEC") in the future. The forward-looking statements included in this presentation represent the Company's views as of the date of this presentation. The Company anticipates that subsequent events and developments will cause its views to change. However, while the Company may elect to update these forward-looking statements at some point in the future, it specifically disclaims any obligation to do so. These forward-looking statements should not be relied upon as representing the Company's views as of any date subsequent to the date of this presentation. This presentation may not be reproduced, forwarded to any person or published, in whole or in part.

2

AMR: GLOBAL CHALLENGE

We must prepare our public health systems to fight multiple threats, simultaneously. Now is the time to address our current antimicrobial-resistant threats, while simultaneously preparing for unknown emerging threats in the future.*

Unmet Medical Need:

CDC/FDA classification:

• C. difficile: urgent threat requiring new antibiotic development;
• MRSA, VRE, PRSP serious threats

RE-EMPHASIZED PRIORITY PATHOGENS

ACURX: COMPANY MISSION

• Develop new class of antibiotics for difficult-to-treat bacterial infections
• Lead DNA pol IIIC Inhibitor discovered by Wright/Brown, Professors Emeriti, UMass;
• First of a new class of antimicrobials** addresses global crisis of AMR
• Previously unexploited bacterial target - DNA pol IIIC -critical for DNA replication of certain Gram-positive bacteria

ACCUMULATING

DATA

*Excerpted from: CDC. COVID-19: U.S. Impact on Antimicrobial Resistance, Special Report 2022. Atlanta, GA: U.S. Department of Health

and Human Services, CDC; 2022.https://www.cdc.gov/drugresistance/covid19.html3 **Patented to May 2032 with 10 years regulatory exclusivity from FDA approval (QIDP and NCE)

Acurx compounds block the active site of the Gram+ specific bacterial enzyme DNA polymerase IIIC (pol IIIC), inhibiting DNA replication

Acurx Technology and Pipeline

DNA Polymerase IIIC Inhibition:

• Innovation criteria1:
• • New chemical class
  • New target
  • New MOA
  • No cross-resistance

Gram-Positive Selective Spectrum (GPSS™) antibiotics target all low G + C bacterial pathogens (including C. difficile, MRSA, VRE, DRSP) - FDA QIDP/Fast Track designated/eligible

• Ibezapolstat (oral) potential for first-line treatment

of C. difficile Infection

Ibezapolstat Phase 2:

 Phase 2a: efficacy results = 100% Clinical Cure and

Sustained Cure (n=10)(CID, 2022) provide clinical validation for targeting pol IIIC

• • Microbiome restoration/sparing and bile acid ratio may inhibit recurrence2
• Phase 2b:
• • Randomized, blinded, vancomycin-controlled; n=32 successful completion and early discontinuation
  • Based on observed aggregate blinded data both treatment performed as expected
  • High rate of Clinical Cure (Primary Efficacy endpoint) observed without any emerging safety concerns
  • Data will be analyzed and topline efficacy results will be reported as soon as possible
  • Successful milestone will allow advancement of this first-in-class antibiotic candidate to Ph3 clinical trials more expeditiously

1Theuretzbacher, WHO, 2017; 2Garey ,CID, 2022

4

Systemic GPSS™ Antibiotic: Program Highlights

• Systemic Pol IIIC Inhibitor Program: Systemic treatment of Staphylococcus, Streptococcus and Enterococcal infections, including MRSA, VRE, and other resistant G+ bacterial infections; WHO/CDC Priority Pathogen Lists1
• • Novel bactericidal mechanism of action, inhibiting DNA pol IIIC, present in G+ but not in G- bacteria or mammals2
  • Bacteria resistant to current antibiotics, including daptomycin, telavancin, ceftaroline, new tetracyclines & linezolid-resistant bacteria
  • In hospitalized patients in the United States, MRSA accounted for 52% of all infections, almost twice as many as MDR Gram-negative infections3
  • VRE hospital infections exceeded carbapenem-resistant (CR) Acinetobacter, MDR Pseudomonas aeruginosa, and CR Enterobacteriaceae infections combined3
• Potential Clinical Indications for Oral and IV Products:
• • Acute bacterial skin and skin-structure infections (including those caused by MRSA)
  • Community-acquiredbacterial pneumonia, hospital and/or ventilator-associated bacterial pneumonia; bacteremia with or w/o infectious endocarditis; bone/joint infections & diabetic foot infections

1 CDC Antibiotic Resistance Threats in the U.S., 2019, Atlanta, U.S. Department of Health and Human Services, CDC, Nov. 2019; 2 Xu, et al., Bioorganic & Medicinal Chemistry https://doi.org/10.1016/j.bmc.2019.06.017; 3Jernigan, et al., Multidrug-Resistant Bacterial Infections in U.S. Hospitalized Patients, 2012-2017,

N Engl J Med 382:1309-19; (2020)	5

Systemic GPSS™ Antibiotic: Program Status

Hit-to-Lead testing of >500 novel compounds has resulted in significant advances:

• In vitro & in vivo safety
• Oral and IV efficacy in mouse infection models including in neutropenic mice (MRSA systemic & thigh, VRE thigh, and PRSP lung)

Lead Optimization: Improve drug-like properties:

• Advanced molecular modeling based on improved leads
• Collaboration with Leiden University Medical Center:
• • High-throughputmeasurement of pol IIIC inhibition
  • 3D structure elucidation of pol IIIC enzyme alone and bound to Acurx inhibitors
  • Design of new compounds based on 3D target binding site data
• Prodrug approaches for both oral & IV delivery
• Current priority: development of oral antibiotic for MRSA/MSSA in ABSSSI to speed advance into clinic

Early 3D Image Map: VRE Pol IIIC

6

ACXIbezapolstat:-362EHighlightsInvestigating C. difficile Efficacy and Disclosures

Anti-recurrence Properties

Clinical development program included a new method to assess for anti-recurrence properties

	Phase I study: Healthy volunteers		Preservation of
	High Stool Concentrations Microbiome changes
	distinct from vancomycin	secondary bile acids

MAX: >3,000 ug/g stool

Stool: ug/g stool

IBZ

Baseline

VAN

Phase 2a study: 10 patients with confirmed C. difficile infection

100% sustained	Preservation of
microbial taxa
clinical cure with	known to
no recurrence	metabolize
	primary bile acids

7

Ibezapolstat: Anti-virulence, Microbiome and MDRO properties

REDUCED FLAGELLA

MOVEMENT1 in concert with reduced expression of primary genes used to synthesize flagella

Ibezapolstat (mg/L)

EFFECTIVE AGAINST MDRO STRAINS1: C. difficile strains with reduced susceptibility to MET, VAN, FDX were susceptible to ibezapolstat susceptibility to metronidazole, vancomycin, or fidaxomicin were susceptible to ibezapolstat, confirming its unique exposto IB

REDUCED TOXIN

PRODUCTION2

60

Toxin production 10^6 CFU/mL

inoculum R20291

Concentration

40

20

0

Toxin A

Toxin B

Toxin A Toxin B

24h

control

48h

EFFECTIVE C. difficile

KILLING IN BIOFILMS3

HUMANIZED MOUSE MODEL4

Microbiome disruption similar to fidaxomicin VAN &MET>>>

IBZ & FDX

		1Basseres et al, ECCMID, 2023; Bassères et al. 2Anaerobe 2022 poster # PII-25; Bassères et al. 3ECCMID 2023 poster #3422/P2144;	8
		Bassères et al. Clostpath 2023 poster #121; 4Jo et al. Clostpath 2023 poster #79

Promising Signals for Ibezapolstat

Factors that provide confidence in successful outcomes of future clinical trials:

• Nonclinical
• • Bactericidal potency vs C. difficile
  • Effective against MDR strains
  • Does not trigger sporulation or toxin release
  • Reduced flagellar movement
  • Active in biofilms
  • Microbiome disruption similar to FDX in humanized mouse model
• Clinical
• • Excellent human safety profile
  • 100% Clinical Cure at EOT in Ph2a (n=10)
  • 100% Sustained Cure at Ph2a follow up
  • High human fecal concentrations (>1000x MIC)
  • Rapid eradication of C. difficile (by Day 3) in patients
  • Favorable microbiome effects by day 3 while on treatment
  • Favorable effect on bile acids
  • High aggregate Clinical Cure rate in Ph2b (n=32)

9

Ibezapolstat: Killing the Bug but Sparing the Microbiome

• Evaluation of potential anti-recurrence properties earlier in clinical trials could become the new standard for anti-C.difficile drug development
• Knowledge of novel MOA (DNA inhibitor) led to testable hypotheses of anti-virulence properties and effectiveness against MDR strains
• Nonclinical pharmacology and clinical results support the continued development of ibezapolstat for treatment of CDI
• Ibezapolstat activity validates DNA pol IIIC as a clinical target
• Features of ibezapolstat pharmacology, including gut microbiome- sparing in patients with CDI; may be a class effect of DNA pol IIIC inhibitors

10