Ampio Pharmaceuticals : – Management Presentation 2020

Management Presentation

Non-Confidential Presentation

Forward-Looking Statement

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Statements and information, including forward-looking statements, speak only to the date they are provided (unless an earlier date is indicated), and we do not undertake any obligation to publicly update any statements or information, including forward-looking statements, whether as a result of new information, future events or otherwise, except as required by law.

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Investment Highlights

Ampion is a first in-class novel biologic positioned to address an unmet medical need with a large global market

3

Ampio Pharmaceuticals

Advancing Immunology Based	Safe and Effective Therapies
Therapies for Prevalent	for Which Limited Treatment
Inflammatory Conditions	Options Exist
Proprietary Manufacturing and
Key Market Entry Advantages
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Ampion is positioned as the first novel biologic for Osteoarthritis of the Knee (OAK)

Global Opportunity for

Widespread Disease &

Ampion Poised to

Effective Care

Billions in U.S. Spending

Address Unmet Need

Billions)5

200+

17+

$29

MILLION

MILLION

($

$28

STANDARD OF CARE FALLS

PEOPLE WORLDWIDE

PEOPLE IN THE U.S.

Spending

12-Year Exclusivity

Global Patents

$27

SHORT FOR SEVERE OAK

UNMET MEDICAL NEED

17+MM	21MM
United States
	Europe 1
		(Millions)	18					NSAIDs		Knee
		16					Steroids
							Opioids	HAs	Surgery
	Japan 2	Disease	14					Addictive + No Long Term Use
	12
	25MM
		U.S.	10					Reimbursement Issues
			2018	2020	2022	2024	2026
18MM	37MM

Brazil 3	China 4	OAK Spending OAK Prevalence

12-year FDA exclusivity and	Multi-billion dollar yearly	Ampion is the only product with
global patents protect position	spending for OAK-related U.S.	demonstrated efficacy
in major world markets	health care costs	in severe OAK
1Kingsbury, Rheumatology, 2014 / 2Yoshimura, J of bone and mineral metabolism, 2009 / 3Coimbra, Clinics, 2019 / 4Liu Q, OA and Cartilage, 2018 / 5Arthritis Foundation "Arthritis by the Numbers", 2017	5

OAK is a progressive and incurable disease

MILD	MODERATE	SEVERE	UNMET NEED
(KL 2)	(KL 3)	(KL 4)	Few treatment
Cartilage begins to	Gaps in cartilage	Cartilage loss
options
erode	reach bone	(~60%)	Invasive, addictive;
Possible joint-	Moderate joint-	Severe joint-space
Opioids
space narrowing	space reduction	reduction	Total Knee
Cycle of	Cycle of	Cycle of
Replacement
Inflammation	inflammation	inflammation	(TKR)
	All patients will progress to severe OAK
KL: Kellgren Lawrence x-ray classification of OAK disease severity		6

Ampion product overview

Ampion is a novel biologic for OAK

• Human serum albumin (HSA) contains low molecular weight components withanti-inflammatory properties
• Theseanti-inflammatory components are produced by the body and are naturally safe

• Sterile HSA products have been safely administered to humans intravenously in high doses for over 60 years
• Although not suitable forintra-articular (IA) injection, HSA's safety profile supports the use of a low-molecular weight IA-injection

• Ampio uses a proprietary filtration method to isolate theanti-inflammatory factors in commercial HSA to allow for IA-injection
• The result is Ampion:
  a novel anti-inflammatory immunomodulating biologic

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Ampion's immunomodulatory action regulates the innate immune response:

Ampion targets cytokine transcriptional pathways to interrupt the OAK disease process

OAK Disease Process

Ampion Treatment

DAMPs

Innate

Immune Cell

Ampion

		Cell nucleus
	Represses Inflammatory	Activates Anti-Inflammatory
Cell nucleus	Cytokine Production	Cytokine Production
		Signaling
NFκB		Protein
		T-factor

Inflammatory	Anti-inflammatory
Cytokines	Cytokines
(TNFα, IL-1β,IL-6,IL-12)	(IL-10, TGFβ)
Inflammatory Response	Anti-Inflammatory Response

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Ampion's immunomodulatory action regulates the innate immune response:

Ampion targets cytokine transcriptional pathways to interrupt the OAK disease process

Continuous cycle of	Ampion in vitrotreatment	Ampion in vitrotreatment	Ampion treatment
disease and joint	represses inflammatory	activates anti-	reduces pain and
inflammation	proteins	inflammatory proteins	disability

• Ampion has a novel mechanism to address inflammatory conditions
• • Ampion, a biologic mixture of active ingredients, modulates multiple pathways involved in the innate immune response as demonstratedin vitro
• Mechanism of Action (MoA)
• • Ampion represses the transcription of inflammatory cytokines correlated with pain, inflammation, and joint damage
  • Ampion activates thegene-transcription of immunomodulating proteins responsible for resolving inflammation
• Targets associated with osteoarthritic pain and disability
• • Ampion represses NFκB induced transcription which reduces the production of the inflammatory cytokines, including TNFα,IL-1β,IL-6
  • Ampion upregulates the transcription of theanti-inflammatory cytokine IL-10

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Building on a platform technology

Ampion Market Expansion

Opportunities

•Immunomodulatory mechanism of action provides a foundation to support use as a disease modifyingOA drug

•Promising in vitroresearch studies indicate Ampion signals cartilage growthand tissue repair 1,2

•Promising early human trials found that Ampion significantly delayed the time to total knee replacementsurgery and reduced narrowing of the joint space 3,4

•Overlapping mechanism of actions indicate potential in other inflammatory conditions

•Proof of concept clinical data in the hand supports safety in other joints

1Bar-Or, et al. Stem Cells Trans Med, 2015 / 2Hausberg, et al. Clin and Exp Rheum, 2018 /

3Schwappach et al. Patient Safety in Surgery, 2018 / 4Schwappach et al. WOA Presentation, 2019	10

Proprietary manufacturing with competitive cost advantage

Traditional Manufacturing	Manufacturing At Ampio
Profitable	Single-use technologies and modular design drive cost advantages
Proprietary	Delivers competitive cost of goods 10x lower than industry benchmark1
Compliant	Built to meet international quality standards and global demand
TransferableDesigned for rapid adoption at additional manufacturing sites
1Basu et. al., J Pharm Innov, 2008		11

Commercial-ready manufacturing with competitive cost advantage

< $200 C	OST				> $100K VALUE
1 Bottle of HSA	Pooling	Ultrafiltration	Sterile Filtration	Filling	83 Finished Vials
		HSA
HSA

• Manufacturing facility has passed recent internal audit for FDA readiness
• Process validation runs successfully completed for regulatory application
• In house manufacturing advantages:
• • Contract manufacturing can be more than 15x more expensive per vial
  • Process development
  • Direct manufacturing and quality assurance experience
• Single use closed systems and automated equipment low cost of goods sold
• Facility capacity of 8 million vials/year

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Building on a foundation of Ampion clinical efficacy to address severe OAK

PAIN

REDUCTION

Severe OAK

All OAK

FUNCTIONAL

IMPROVEMENT

Severe OAK

All OAK

	SPA	•FDA awards Special Protocol Assessment (SPA)
	agreement for study design
AP-013
AP-003-C
40%	37%	•Efficacy is demonstrated in study of
		severe OAK patients

				Pain	Function
		AP-004			AP-003-B
33%	32%			39%	33%	41%	39%	•Ampion treatment effect is
29%
25%				reproducible in severe OAK
Pain		Function	Pain	Function
			AIK Study		AP-003-A
			48%		42%	37%	35%	35%	•FDA confirms
Clinically Meaningful						AP-003-A as first of
20% improvement1									two pivotal trials
			Pain			Pain	Function

Outcomes from each trial inform next steps in Ampion's clinical progression (Phase I - III)

1Salottolo & Stahl, J Orthopaedics, 2018; Dworkin et. al., J Pain, 2008

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Ampion provides a consistent and meaningful clinical effect in OAK

Reduced Pain (%) WOMAC A

Improved Function (%) WOMAC C

Improvement in pain with Ampion treatment

AP-003-AAP-003-C

Ampion

Saline

Ampion

Saline

25%

30%

42%40%

Improvement in function with Ampion treatment

35%37%

27%26%

Ampion Saline Ampion Saline

AP-003-AAP-003-C

• Reproducible results from first pivotal to most recent severe OAK trial across time, clinical sites, and patients
• Clinically meaningful effect with Ampion treatment in pain reduction and functional improvement
• Provides confidence moving into studyAP-013 conducted under SPA agreement from FDA

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Ampion delivers a significant effect in severe OAK

Improvement in pain with Ampion treatment

0	2	6	10	12

(%)
ReducedPain WOMACA										26%
							Saline (n=247)				Ampion (n=338)	36%
		Improvement in function with Ampion treatment
(%)												34%
FunctionImproved CWOMAC												27%
0	2	6	10	12
						Saline (n=247)			Ampion (n=338)

• An integrated analysis of all severe OAK patients from Ampion single- injection studies demonstrates a significant and meaningful effect of Ampion
• Increased patient number highlights Ampion is statistically significant
  (p < 0.05) compared to placebo (saline) in improving pain and function
• Demonstrates strength of studyAP-013 conducted under SPA agreement from FDA

Integrated analysis performed on all KL 4 subjects from studies AP-003-A,AP-003-B,AP-003-C & AP-004

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Special Protocol Assessment (SPA) trial currently underway

	Data-driven Trial Design With SPA Assurance
Timeline	Day -28	Baseline	Weeks	Week 12	Week 24
to Day 0	(Day 0)	1 - 11
Event	Screening	Ampion	Safety &	Primary	Final
Efficacy
Injection	Endpoint	Assessment
		Assessments
			12 Weeks
		FDA Agreement

• Randomized,double-blind,placebo-controlled, multicenter US trial
• Single,intra-articular injection of Ampion in severe OAK patients
• Pain and function assessed asco-primary endpoints at 12-weeks post- injection
• Trial to enroll 1,034 patients
• Interim analysis allowssample-size recalculation for conservative approach

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Sustained safety and efficacy with continued treatment

Ampion continues to be safe and effective after repeat injections

Ampion Provides a Clinically Meaningful Reduction in Pain

for up to One Year

1st Injection

2nd Injection

3rd Injection

4th Injection

5th Injection

• Continued efficacy observed with single injections every12-weeks
• Safety profile supports up to 5 injections per year
• Reimbursement strategy

WOMAC A

Reduction in Pain (%)

47% pain reduction

after 5 injections

Fewer Safety Related Events for Ampion

Compared to Other Products1

Data from all trials show that Ampion is safe and well-tolerated

• More than 1000 patients treated
• Safety profile more favorable than other products available to treat mild/moderate OAK

Safety Events (%) Related to Product

< 1%

4%6% 6% 7%

10%

27%

13%

1Sourced from Summary of Safety and Effectiveness (SSED) documents for all products except Zilretta, which was sourced from Conaghan et. al., J Bone Joint Surg Am., 2018

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Ampion value-creating milestones

	2019	2020
	Expected
✓	FDA Approves AP-013	AP-013 Fully Enrolled
Design with SPA
✓		AP-013 Week 12
AP-013 Trial Initiated	Primary Endpoint Results
	AP-013 Week 24 Complete
✓
AP-013 Interim Analysis
Enrollment Complete	Ampion BLA Filing
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Ampio Pharmaceuticals

FOUNDED ON	Backed by scientific
SCIENCE	and clinical evidence
SAFETY	Over 2,000 patients treated
FIRST	with no serious side effects
READY FOR	Late stage clinical development
MARKET	with de-risked regulatory path
LEAN AND	Proprietary manufacturing
EFFICIENT	drives low cost of goods
GLOBAL	Growing epidemic and billions
OPPORTUNITY	in healthcare spending
MEETING	Addressing severe disease to
UNMET NEEDS	improve life for those in need
ADVANCING	Developing safe and effective
IMMUNOLOGY THERAPIES	products for prevalent diseases
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