180 Life Sciences : Corporate Presentation

NASDAQ: ATNF

Leading Research into Solving One of the World's

Largest Drivers of Disease: INFLAMMATION

Corporate Presentation

March 2024

Disclaimer

This Presentation is for informational purposes only and does not constitute an offer to sell, a solicitation of an offer to buy, or a recommendation to purchase any equity, debt or other financial instruments of 180 LIFE SCIENCES Corp. ("180 Life Sciences" or the "Company") or any of its affiliates. This

Presentation has been prepared to assist interested parties in making their own evaluation with respect to the business of 180 LIFE SCIENCES and for no

other purpose. The information contained herein does not purport to be all-inclusive. The data contained herein is derived from various internal and external sources. No representation is made as to the reasonableness of the assumptions made within or the accuracy or completeness of any projections or any other information contained herein. Any data on past performance or projections contained herein is no indication as to future performance. 180 LIFE SCIENCES assumes no obligation to update the information in this Presentation.

Forward-Looking Statements

This Presentation includes "forward-looking statements" within the meaning of U.S. securities laws. Words such as "expect," "estimate," "project," "budget,"

"forecast," "anticipate," "intend," "plan," "may," "will," "could," "should," "believes," "predicts," "potential," "continue" and similar expressions are intended to identify such forward-looking statements. These forward-looking statements involve significant risks and uncertainties that could cause the actual results to differ materially from the expected results and, consequently, you should not rely on these forward-looking statements as predictions of future events. These forward-looking statements and factors that may cause such differences include, without limitation, statements relating to the company's continued listing on the Nasdaq Stock Market; expectations regarding the future capitalization, resources and ownership structure of the company; the inability to recognize the anticipated benefits of the business, which may be affected by, among other things, the ability of the company to execute its plans to develop and market new drug products and the timing, costs and results of these development programs; estimates of the size of the

markets for the company's potential drug products; potential litigation involving the company; the validity or enforceability of the company's intellectual

property, including any challenges thereto; global economic conditions; geopolitical events and regulatory changes; access to additional financing; the duration and ongoing impact of the COVID-19 pandemic; and other risks and uncertainties indicated from time to time in the company's filings with the Securities and Exchange Commission (the "SEC"). The foregoing list of factors is not exclusive. Additional information concerning these and other risk factors is contained in the company's most recent filings with the SEC. All subsequent written and oral forward-looking statements concerning the company and attributable to the company or any person acting on its behalf are expressly qualified in their entirety by the cautionary statements above. Readers are cautioned not to place undue reliance upon any forward-looking statements, which speak only as of the date made. The company does not undertake any obligation or undertaking to release publicly any updates or revisions to any forward-looking statement to reflect any change in its expectations or any

change in events, conditions or circumstances on which any such statement is based.

180 Life Sciences Corp.

www.180lifesciences.com

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180 Life Sciences Overview

Robust IP-Protected Product Pipeline with Large Market Potential

• Three families of drugs address significant market opportunities in inflammation, fibrosis and pain with multiple programs in synchronized stages of development

⎼ Fibrosis & Anti-TNF

• • Synthetic CBD Analogs (SCAs)
  • a7nAChR
• Strong IP Portfolio: 24 granted patents, 33 filed patent applications

Numerous Near-Term Inflection Points

• Anti-TNFprograms: expecting to initiate a Phase 2 trial in 2024 in POCD
• SCA programs: validation ongoing, with a planned PK study

Scientific Pioneers Backed by Experienced Operators and Board

• Founders: pioneers with 100+ cumulative years of discovery and clinical experience; successes include Remicade and Tysabri
• Board: seasoned and diverse executives with broad skillsets that complement the
  Company's needs
• Senior Management: operators with decades of experience at large & small life sciences companies

180 Life Sciences Corp.

www.180lifesciences.com

Leading Research into Solving One of

the World's Largest

Drivers of Disease:

INFLAMMATION

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Three Therapeutic Families Targeting Multiple Indications

	Indication	Early-Stage Development	Late-Stage Development	Milestones
		Discovery/Validation	Phase 1	Phase 2	Phase 3
	Dupuytren's	adalimumab				Planning Phase 3
	Contracture
						UK feasibility study
	Frozen Shoulder	adalimumab				closed, new clinical
Fibrosis &				trial site and country
					to be determined
Anti-TNF*
	POCD	infliximab				Initiate Phase 2
				2024
	NASH					Ongoing
					Validation
Synthetic	Chronic Pain					Ongoing
				Validation
CBD Analogs	Weight Loss /					Ongoing
(SCAs)
	Early Arthritis					Validation
Nicotine	Smoking Cessation
Acetylcholine					Ongoing
Induced Ulcerative
Receptor					Validation
Colitis
(α7nAChR)

*Repurposed drugs in new indications may not need to follow standard regulatory approval pathways. Regulatory approvals obtained from the MHRA and CCMO and the relevant accredited ethics committees to perform clinical trials in the UK and The Netherlands. No marketing applications or requests for marketing approval have been submitted to the FDA for any products at this time.

180 Life Sciences Corp.

www.180lifesciences.com

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Experienced Leadership Team

		Management Team
	James Woody, MD, PhD	Jonathan Rothbard, PhD	Ozan Pamir
	Director, CEO	Chief Scientific Officer	Chief Financial Officer
		Founders
	Prof. Sir Marc Feldmann	Prof. Lawrence Steinman	Prof. Jagdeep Nanchahal
	Co-Founder	Executive Chairman	Co-Founder; Chair,
	University of Oxford	Co-Founder	Clinical Advisory Board
		Stanford University	University of Oxford
		Board of Directors
Prof. Lawrence Steinman	James Woody, MD, PhD	Blair Jordan	Omar Jimenez	Ryan Smith
Chairman	Chief Executive Officer	Lead Director	Director	Director

180 Life Sciences Corp.

www.180lifesciences.com

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Fibrosis & Anti-TNF Therapeutics: Lead Clinical Indications

Dupuytren's Contracture

Frozen Shoulder

POCD

Novel Treatments for TNF-Driven Conditions

• All three conditions are primarily driven by a pro-inflammatory protein called tumor necrosis factor (TNF)
• Proof-of-Conceptin Dupuytren's Contracture has broader applications in Frozen Shoulder and POCD
• • No treatment options currently available that target and prevent early-stage fibrosis of the hand
  • Treating early-stage fibrosis can halt disease progression
  • Clinically significant Phase 2b data in Dupuytren's Contracture, published in The Lancet Rheumatology
  • Phase 2b clinical data in Dupuytren's Contracture provides a strong rationale to investigate anti-TNF treatment in Frozen Shoulder and POCD
• Shorter development timeline for repurposing drugs
• • Can leverage previous studies and clinical data of anti-TNF approved drugs
  • Studies typically commence at Phase 2 and are potentially pivotal

180 Life Sciences Corp.

www.180lifesciences.com

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Initial Indication Targeting Dupuytren's Contracture

Characteristics

• Common localized fibrotic condition of the hand, develops over years

• Nodules form under skin - eventually creating a thick cord pulling one or more fingers

• Can limit hand functions

• Unlike liver and lung fibrosis, can be identified early

Early Disease	Late Disease - Results in Impaired Hand Function

No approved treatment

Large unmet need

Phase 2b trial treated early disease

(1) Layton T & Nanchahal J. F1000Research 2019, 8(F1000Faculty Rev): 231

Current treatment options suboptimal:(1)

• Surgery - long (3 month) recovery, 6% recurrence at 5yr
• Needle perforation - less invasive, 30% recurrence at 5yr
• Collagenase injections - office procedure, 47% recurrence at 5yr

180 Life Sciences Corp.

www.180lifesciences.com

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Phase 2a Completed: 40mg (in 0.4ml) Adalimumab is Effective

The First Trial of Any Targeted Therapy in Early Dupuytren's Contracture

Anti-Tumour Necrosis Factor Therapy for Dupuytren's Disease: A Randomized Dose Response Proof of Concept Phase 2A Clinical Trial(1)

Trial Overview

Adalimumab injected directly into the nodule

1. • Dose ranging with 28 patients
   • 40 mg in 0.4ml - effective dose
   • Funded by HICF (Wellcome Trust + Dept of Health) and 180 Life Sciences
2. EBioMedicine 33 (2018) 282-288

180 Life Sciences Corp.

Demonstrated Efficacy at High Concentration & Dose

						p=0.019
5.0			p=0.024	1250
	p<0.001
	p=0.006
4.0				1000
3.0				750
2.0				500
1.0				250
0.0				0.0
Placebo	15mg	35mg	40mg	Placebo	15mg	35mg	40mg
	adalimumab			adalimumab
	Treatment
Placebo	(1.51 ± 0.65)		35mg in 0.7ml* (1.44 ± 0.48)
15mg in 0.3ml	(1.60 ± 0.67)		40mg in 0.4ml	(1.09 ± 0.89) *Leakage observed from site injection due to large volume
www.180lifesciences.com						8

Phase 2b Study in Patients with Dupuytren's Contracture

Patient Recruitment

Patients with early-stage Dupuytren's Contracture and a clinically distinct nodule with a clear history of progression in the preceding six months

N=140 (UK Only)

randomization

1:1

9-monthdouble-blind

treatment course

optimal dose of adalimumab: four 40mg injections in 0.4mL at baseline

placebo

Follow-up

Primary Endpoint:

nodule hardness

at 12 months measured with a durometer

Secondary Endpoint:

nodule size measured

using an ultrasound

scan at 12 and 18 months

Month

first	3	6	9
dose

Description

12 months:

Primary and Secondary

Endpoints measured

18 months:

Secondary Endpoint

measured

• Randomized, placebo-controlled clinical trial in patients with early-stage Dupuytren's injected with optimal dose adalimumab
• Every 3 months for 1 year (4 injections), following for a total of 18 months
• Outcome measures include nodule hardness, size and disease progression
• Randomized 181 patients across 3 sites in the UK (Oxford, Edinburgh) and Netherlands (Groningen)

180 Life Sciences Corp.

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Phase 2b: Primary and Key Secondary Endpoint Met

Endpoints selected as reductions potentially indicate disease no longer progressing

p=0.025 p<0.0001

p=0002p<0.0001

Nodule hardness -4.6 AU at 12 months	Nodule size -8.4mm2 at 12 months
Nodule hardness -5.8 AU at 18 months	Nodule size -14.4mm2 at 18 months

Results were clinically significant vs. placebo

180 Life Sciences Corp.

www.180lifesciences.com

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