PainReform : Investors Presentation – March 2024

Investor Presentation

March 2024

Forward-Looking Statements

This presentation contains forward-looking statements about our expectations, beliefs and intentions. Forward-looking statements can be identified by the use of forward-looking words such as "believe", "expect", "intend", "plan", "may", "should", "could", "might", "seek", "target", "will", "project", "forecast", "continue" or "anticipate" or their negatives or variations of these words or other comparable words or by the fact that these statements do not relate strictly to historical matters. These forward-looking statements are based on assumptions and assessments made in light of management's experience and perception of historical trends, current conditions, expected future developments and other factors believed to be appropriate. Because forward-looking statements relate to matters that have not yet occurred, these statements are inherently subject to risks and uncertainties that could cause our actual results to differ materially from any future results expressed or implied by the forward-looking statements. Many factors could cause our actual activities or results to differ materially from the activities and results anticipated in forward- looking statements, including, but not limited to, the following: our history of significant losses, our need to raise additional capital and our ability to obtain additional capital on acceptable terms, or at all; our dependence on the success of our initial product candidate, PRF-110; the outcomes of preclinical studies, clinical trials and other research regarding PRF-110 and future product candidates; the impact of the COVID-19 pandemic on our operations; our limited experience managing clinical trials; our ability to retain key personnel and recruit additional employees; our reliance on third parties for the conduct of clinical trials, product manufacturing and development; the impact of competition and new technologies; our ability to comply with regulatory requirements relating to the development and marketing of our product candidates; commercial success and market acceptance of our product candidates; our ability to establish sales and marketing capabilities or enter into agreements with third parties and our reliance on third party distributors and resellers; our ability to establish and maintain strategic partnerships and other corporate collaborations; the implementation of our business model and strategic plans for our business and product candidates; the scope of protection we are able to establish and maintain for intellectual property rights and our ability to operate our business without infringing the intellectual property rights of others; the overall global economic environment; our ability to develop an active trading market for our ordinary shares and whether the market price of our ordinary shares is volatile; and statements as to the impact of the political and security situation in Israel on our business. More detailed information about the risks and uncertainties affecting us is contained under the heading "Risk Factors" included in the Company's most recent Annual Report on Form 20-F and in other filings that we have made and may make with the Securities and Exchange Commission in the future.

These statements are only current predictions and are subject to known and unknown risks, uncertainties and other factors that may cause our or our industry's actual results, levels of activity, performance or achievements to be materially different from those anticipated by the forward-looking statements. Given these uncertainties, you should not rely upon forward-looking statements as predictions of future events.

All forward-looking statements attributable to us or persons acting on our behalf included in, but not limited to, this presentation speak only as of the date hereof and are expressly qualified in their entirety by the foregoing. We undertake no obligations to update or revise forward-looking statements to reflect events or circumstances that arise after the date made or to reflect the occurrence of unanticipated events. In evaluating forward-looking statements, you should consider these risks and uncertainties.

This presentation shall not constitute an offer to sell or the solicitation of an offer to buy, nor shall there be any sale of these securities in any state or other jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or other jurisdiction.

The presentation contains information about investigation-stage drug products under development, which have not yet been approved by the FDA for commercial distribution in the United States. All representations in this presentation are based upon investigations in certain clinical and other research, but which accordingly should not be construed as general claims for the safety or efficacy of the products when used by patients.

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PainReform Ltd.| www.painreform.com

Post Operative Pain Management

PRF-110 Executive Summary

• Post-operativepain treatment is a growing market (~$12B) with a need for better therapeutics

1. Local anesthetics provide pain relief for up to 6 hours and require augmentation with non-steroidalanti-inflammatory drugs (NSAIDs)

1. NSAIDs or opioids for moderate to severe pain, leading to side effects and dependence

1. Opiate abuse and addiction cause 70,000 death in the US & an economic burden of $80B/yr

• 1. Exparel (Pacira), a marketed long-acting liposomal generic local anesthetic has >$500M revenues: PCRX-market cap, at peak, over $4.0B - an important benchmark for PainReform
• PainReform has developed PRF-110, a novel formulation extended release ropivacaine

1. In a Phase 2 clinical study clinical study in 15 open hernia patients PRF-110 demonstrated pain relief of up to 72 hours

1. Phase 3 study underway in the USA

1. Patent estate granted for PRF-110 and formulation platform through 2033 prior to extensions-for US, Canada, EU, Israel, Australia, China, Japan, Russia, and other countries

• 1. Efficient manufacturing process for PRF-110 in the USA
• Highly experienced board of directors and management team
• Inhouse clinical, manufacturing and QA know-how

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PainReform Ltd.| www.painreform.com

Post Operative Pain Management

Post-Operative Pain Management Market Overview

• The 2017 North America post-operative pain treatment market was estimated at ~$12B and is expected to reach ~$16B and $45B world-wide by the end of 20261

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• Significant unmet need for long-acting local anesthetic agents in order to spare opioids use, their side effects and reduce hospital length of stay due to complications
• Over 50 million procedures in the US per year
• • Just 10 % share provides over $500M in US revenues
• Despite the extensive use of opioids and NSAIDs, 74-86% of patients still experience moderate-to-extreme pain after surgery2
• Study of the global post-operative pain management market reveals a steady growth potential of 5.4% CAGR during the forecast period of 2017 to 20234

1. https://www.persistencemarketresearch.com/market-research/postoperative-pain-management-market.asp

2 Gan, et al.,. Incidence, patient satisfaction, and perceptions of post-surgical pain: results from a US national survey. CurrMed Res Opin. 2014;30(1):149-160.

3. https://www.medgadget.com/2018/06/post-operative-pain-management-market-2018-increasing-number-of-surgeries-has-led-to-grow-at-a-cagr-of-5-4-in-healthcare-industry- asserts- mrfr.html#:~:text=Global%20Post%2Doperative%20pain%20management,during%20forecasted%20period%202017%2D2023.&text=Increasing%20number%20of%20surgerie s%20and,the%20growth%20of%20the%20market.

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PainReform Ltd.| www.painreform.com

Post Operative Pain Management

Current Approaches in Post-Operative Analgesia Are Lacking

Short-Acting Opioids

• Repeated dosing required
• Inconsistent pain control between doses
• Dependence risk increases with treatment duration

Long-Acting Opioids

• Poor efficacy in acute pain control
• Not intended for the treatment of post-operative pain

Significant adverse effects including respiratory depression, sedation and postoperative nausea and vomiting

Non-SteroidalAnti-inflammatory Drugs (NSAIDs)

• Moderate efficacy in acute pain control
• Repeated dosing required

• Inconsistent pain control between doses
• Significant safety issues, including bleeding, stroke, gastritis, renal toxicity

Exparel®

• Limited efficacy in acute pain control
• Liposomal bupivacaine
• Reduced postoperative opioid use
• Approved - revenues $500M
• Handling/delivery limitations

Zynrelef®

• Complex, high production-price
• Bupivacaine and Meloxicam leading to a black box on the label
• Approved, launched July 2021
• 2022 revenues - $10.2M

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PainReform Ltd.| www.painreform.com

Post Operative Pain Management

Prescription Opioids

• Prescription opioids can be used to treat moderate-to-severe pain and are often prescribed following surgery or injury
• In recent years, there has been a dramatic increase in the acceptance and use of prescription Opioids
• Opioid's dependency can start within 3 days of initial use
• More than 191 million opioid prescriptions were dispensed to American patients in 2017
• The most common drugs involved in prescription opioid overdose deaths include:
• • Methadone
  • Oxycodone (such as OxyContin®)
  • Hydrocodone (such as Vicodin®)
• Anyone who takes prescription opioids runs the risk of becoming addicted to them
• 99% of surgical patients receive opioids to manage post-surgical pain and are released with opiate prescription
• 6% to 10% of surgical patients discharged with opiate prescriptions develop an opioid-dependency
• One in four patients receiving long-term opioid therapy in a primary care setting struggles with opioid addiction
• In 2016 and 2019, approximately 11.5 million Americans reported misusing prescription opioids in the past year
• Taking too many prescription opioids can stop a person's breathing-leading to death
• 62.6% Of people listed pain as their main reason for opioid misuse, where 36% of people with an opioid problem received a prescription from a healthcare provider

Source: CDC

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PainReform Ltd.| www.painreform.com

Post Operative Pain Management

PainReform Solution: PRF-110 Post Operative Pain Management

• PRF-110has the potential to reduce the consumption of opioids to manage post-surgical pain
• In Phase III clinical study in the US
• Studies have shown 48 hours of pain reduction in healthy volunteers and about 72 hours in a clinical setting
• PainReform has developed a platform formulation for extended release of drugs
• Avoiding multiple injections reduces delivery time and complexity, reduces the risk of hematoma
• Reliable PK and low Cmax
• Physical attributes provide ease of surgeon use
• No injections, thereby avoiding the risk of inadvertent systemic administration
• Platform can be utilized for a wide range of APIs to generate a sustainable pipeline of new product applications
• Low variable costs allows for ease of manufacturing and production to meet high market demand
• Robust IP portfolio

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PainReform Ltd.| www.painreform.com

Post Operative Pain Management

PRF-110 Manufacturing

• Engaged Pharmaceutics International, Inc. (PII):
• • US-basedcontract manufacturing organization (CMO)
  • Well experienced in sterile manufacturing
  • PII is a premier, solutions-oriented,science-driven CMO with over 25 years of proven success in providing high-quality dosage form development
  • cGMP manufacturing services to the global biopharmaceutical industry
• Successfully developed a GMP manufacturing process for PRF-110
• PRF-110is manufactured via a scalable and cost-effective process, is easy to commercialize, and contains excipients that are all FDA-approved as GRAS (generally regarded as safe)
• Low COGS compared to the current drug landscape

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PainReform Ltd.| www.painreform.com

Post Operative Pain Management

PRF-110 Safety

• PainReform carried out extensive FDA-requested wound healing and related animal studies that showed:
• • PRF-110 allows for normal wound healing of surgical incisions equal to both Naropin® and saline without any untoward histological or radiologic (microCT) effects observed in soft or bony tissue
  • Tensile strength of healed surgical skin following exposure to PRF-110 is equal to that of incisions exposed to either Naropin® or saline
  • Integrity of surgical sutures and surgical meshes is not affected by PRF-110 (compared to saline)
  • No systemic side effects were observed in any models
• PRF-110safety in human trials showed no systemic, wound healing or scarring abnormalities. Wound healing in all patients was complete and similar to that expected in surgery without PRF-110

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PainReform Ltd.| www.painreform.com

Post Operative Pain Management

Comparison of PRF-110 Versus Market Leading Product

• Critically required for post-surgical topical applications
• During in vitro tests that were designed to mimic the spreadability attributes of PRF-110:
• • PRF-110demonstrated superior formulation properties with respect to surface-tissue spreading
  • Lower viscosity, PRF-110 1,500 cP vs. about 10,000 cP for the commercial competitor
  • Superior surface interaction with surgical tissue based on a slide test, which demonstrated that the sliding of PRF-110 was twice that of the competitor.
• These results demonstrate that PRF-110 provides unique and significant benefits for local administration in postoperative pain management
• PRF-110excelled in surface/tissue spreading and staying in place-a key advantage in achieving effective post-surgical pain relief-as it is critical to have even distribution inside the surgical wound.

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PainReform Ltd.| www.painreform.com

Post Operative Pain Management