Apellis Pharmaceuticals : March Corporate Presentation

PIONEERING

TARGETED C3 THERAPIES

March 4, 2020

Forward-looking statements

Statements in this presentation about future expectations, plans and prospects, as well as any other statements regarding matters that are not historical facts, may constitute "forward-looking statements" within the meaning of The Private Securities Litigation Reform Act of 1995. These statements include, but are not limited to, statements relating to the implications of preliminary clinical data. The words "anticipate," "believe," "continue," "could," "estimate," "expect," "intend," "may," "plan," "potential," "predict," "project," "should," "target," "will," "would" and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including: whether preliminary or interim results from a clinical trial will be predictive of the final results of the trial; whether results obtained in preclinical studies and clinical trials such as the results reported in this release will be indicative of results that will be generated in future clinical trials; whether

pegcetacoplan will successfully advance through the clinical trial process on a timely basis, or at all; whether the results of the Pegasus or other clinical trials will be sufficient to form the basis of regulatory submissions, whether the Company's clinical trials will warrant regulatory submissions and whether pegcetacoplan will receive approval from the United States Food and Drug Administration or equivalent foreign regulatory agencies for GA, PNH, C3G or any other indication; whether, if Apellis' products receive approval, they will be successfully distributed and marketed; and other factors discussed in the "Risk Factors" section of Apellis' Annual Report on Form 10-K filed with the Securities and Exchange Commission on February 27, 2020 and the risks described in other filings that Apellis may make with the Securities and Exchange Commission. Any forward-looking statements contained in this press release speak only as of the date hereof, and Apellis specifically disclaims any obligation to update any forward-looking statement, whether as a result of new information, future events or otherwise.

2

Apellis: Pioneer in targeted C3 therapies

Positive phase 3 data	Platform potential unlocked:
with p-value <0.0001 on	ophthalmology, hematology,
primary endpoint against	nephrology and gene therapies

eculizumab in PNH

Focused on patients with unmet needs in multiple indications

3

Only company with late-stage C3 therapies across indications

Source: Merle NS, et al. Cell Research. 2010; 20:34-50.

4

Pipeline: Advancing life-changing therapies

Product Category

Hematology

Subcutaneous pegcetacoplan (APL-2)

Nephrology

Intravitreal Ophthalmology pegcetacoplan

Intravenous	Gene therapy
APL-9

PNH

CAD

C3G

GA

AAVs

Disease	Pre-clinical	Phase 1	Phase 1b/2	Phase 3	Approved
Paroxysmal Nocturnal
Hemoglobinuria
Cold Agglutinin
Disease
С3
Glomerulopathy
Geographic
Atrophy
Control of Host
Attack on AAVs for
Gene Therapies

5

Subcutaneous pegcetacoplan

PNH CAD C3G

Device prototype

WHO SHE IS:

Erin is a 25-year-old who is engaged and currently planning her wedding with her fiancé. Diagnosed with PNH in 2019, Erin enjoys nature, as well as relaxing and watching Disney movies. She has aspirations of becoming a mother and owning her own wedding planning business. She is currently taking eculizumab.

GREATEST CHALLENGE:

DEBILITATING SYMPTOMS

EVEN ON TREATMENT

"I think that now the fatigue, it's not as often, but

it's stronger. For instance … I used have a level 6 fatigue every single day. Now, it's more of maybe one day a week, but at a level 10.

My brain is in a fog, or a blur. I don't really feel like talking to anybody. I don't feel like doing anything. If I could sleep

all day, I would just sleep all day. I feel like there's no kickstart

to my brain on those days. Everything is in slow motion. I don't really know

how else to explain it. My body feels like it's a million times heavier than what it is. Trying to just walk, my feet are dragging and my fiancé and I live in an upstairs apartment. Sometimes it takes me 10 minutes just to get up the stairs. Each leg I'm lifting up, it's so heavy. I can't even lift my leg."

Erin has agreed to share her personal views and experience living with PNH. Erin's views and thoughts expressed on this slide belong to her, and not necessarily to the entire PNH patient community. Each patient may have a different experience.

IMPACT OF PNH ON LIFE:

ALWAYS PLANNING

"Any plans that we make, whether it be wedding-related or not, we have to constantly consider where my treatment is. It's extremely annoying. It's frustrating. It's not the end of the world to manage the time around the treatments, but to figure out me just being a nervous wreck. Before we go anywhere I always look for where the closest hospital is, just in case. Definitely bring all my medications and things

like that."

ASPIRATIONS FOR

THE FUTURE:

"My biggest aspiration is definitely to be a mom, which is a little nerve-racking with PNH because I think about how some days my fatigue is so bad. Another big aspiration to me - I've always wanted to own my own business and it was always a big question mark as to what business I wanted to own. Now that I'm really starting to take a passion with the wedding planning, it's definitely a route that I'd like to take as far as owning my own business and wedding planning. Those would probably be my biggest aspirations - to come up with a career7 that I can be my own boss, and also to be a mom."

Pegcetacoplan met its primary endpoint

3.8 g/dL

PNH

Improvement in adjusted means in hemoglobin vs. eculizumab at week 16

p <0.0001

8

PNH

PNH is a rare and life-threatening blood disease

Estimated prevalence of	Historically untreated
PNH worldwide1	patients2

35%

5-year mortality rate

Note: Thrombosis and

hemorrhage are the most common causes of death.

~15,000 patients

Sources: 1. Hill A, et al. Blood. 2006;108(11):985. 2. Hillmen P, et al. N Engl J Med. 1995;333(19):1253-1258.	9

PNH patients on C5 inhibitors continue to have high unmet need

Retrospective studies show:

Up to 70%

of patients continue to have low hemoglobin despite treatment1,2

PNH

100%

of patients had evidence of

C3-opsonized PNH RBCs1

36%

of patients require

• 1 transfusion per year3

1.9x ULN

average absolute

reticulocyte count3

1	Risitano AM, Marotta S, Ricci P, et al. (2019) Anti-complement Treatment for Paroxysmal Nocturnal Hemoglobinuria: Time for Proximal Complement Inhibition? A Position Paper
From the SAAWP of the EBMT. Front. Immunol. 10:1157. doi: 10.3389/fimmu.2019.01157.
2	Risitano AM, Notaro R, Marando L, et al. (2009) Complement fraction 3 binding on erythrocytes as additional mechanism of
disease in paroxysmal nocturnal hemoglobinuria patients treated by eculizumab. Blood. 2009 Apr 23;113(17):4094-100.	10
3	McKinley C. Extravascular Hemolysis Due to C3-Loading in Patients with PNH Treated with Eculizumab: Defining the Clinical Syndrome. Blood. 2017;130:3471.

PNH is characterized by intravascular and extravascular hemolysis

PNH

*Reference: Risitano AM, Marotta S, Ricci P, et al. (2019) Anti-complement Treatment for Paroxysmal Nocturnal Hemoglobinuria: Time for Proximal Complement	11
Inhibition? A Position Paper From the SAAWP of the EBMT. Front. Immunol. 10:1157. doi: 10.3389/fimmu.2019.01157.

PEGASUS: Phase 3 head-to-head trial of pegcetacoplan vs eculizumab

PNH

Baseline

Day 1

4 weeks

Run-in

N=80 pegcetacoplan + eculizumab

APL2-302; NCT03500549

Primary endpoint read out

16 weeks							32 weeks open-label
Randomized period					4 weeks				28 weeks
Group 1, N=41					Group 1,	N=38			Group 1+2,
						N=77
pegcetacoplan					pegcetacoplan
						pegcetacoplan

Group 2,	N=39		Group 2, N=39
	pegcetacoplan
eculizumab
	+ eculizumab

Image not drawn to scale

12

Pegcetacoplan met its primary endpoint (MMRM)

3.8 g/dL improvement in adjusted means in hemoglobin vs. eculizumab at week 16, p<0.0001

PNH

3.8 g/dL

at week 16, p<0.0001

APL2-302; NCT03500549

13

Hemoglobin: Observed data consistent with modeled data

PNH

2.9 g/dL at week 16

APL2-302; NCT03500549

14

Key secondary endpoints analysis

Transfusion

Avoidance n(%)

Reticulocytes1

Mean (SE)

PNH

LDH1

Mean (SE)

FACIT-Fatigue1

Mean (SE)

LDH= Lactate Dehydrogenase. FACIT= Functional Assessment of Chronic Illness Therapy. Mean (SE) = Adjusted means (SE) are based on the mixed model repeated measures (MMRM) analysis. CI= Confidence Interval. SE= Standard Error. Key Secondary Endpoints analyses are based on pre-specifiedNon-Inferiority Margins. Non-inferiority is achieved if the LCL or UCL of the 95% CI of the treatment difference meets the pre-specified margin. *Not Tested: As LDH did not achieve non-inferiority, no other endpoints were tested. 1 = Change from baseline

Non

Inferiority

Yes

Yes

No

Not

Tested*

= Non-inferiority margin for the given endpoint

= Difference between Pegcetacoplan and Eculizumab

= 95% Confidence Interval

15

APL2-302; NCT03500549

85% of patients in the pegcetacoplan group were transfusion free

Pegcetacoplan

85%

transfusion free

at week 16

PNH

Eculizumab

15%

transfusion free

at week 16

Transfusion-free patient

Patient who received transfusion(s)

6 of 41

patients

33 of 39 patients

APL2-302; NCT03500549

16

Observed Data: Reticulocytes, LDH, FACIT-Fatigue

PNH

pegcetacoplan eculizumab

17

APL2-302; NCT03500549

PNH

Frequency of adverse events was similar between groups during the randomized, 16-week period

		Pegcetacoplan N=41	Eculizumab N=39
		n (%)	n (%)
	Any TEAE	36 (87.8)	34 (87.2)
Overview	- Serious AE	7 (17.1)	6 (15.4)
	Discontinuations due to AE	3 (7.3)	0
	All Infections	12 (29.3)	9 (23.1)
Adverse	- Sepsis	0	0
- Meningitis	0	0
events
of interest	Hemolysis	4 (9.8)	9 (23.1)
	Injection site reactions	15 (36.6)	1 (2.6)
	Diarrhea	9 (22.0)	0
Other	Headache	3 (7.3)	8 (20.5)
frequent	Fatigue	2 (4.9)	6 (15.4)
adverse	Abdominal pain	5 (12.2)	4 (10.3)
events
(n ≥ 4)	Back pain	3 (7.3)	4 (10.3)
	Dizziness	1 (2.4)	4 (10.3)

APL2-302; NCT03500549

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Prepared to meet the needs of PNH patients

PNH

Global Medical and Commercial

Organization

Highly

Experienced

Team

"Sometimes it takes me 10 minutes just to get up the stairs. Each leg I'm lifting up, it's so heavy I can't even lift my leg."

- Erin, patient on treatment with eculizumab

Patient Focused

Support and

Access for

Patients

Our Goal: Elevate the standard of care in PNH

19

Promising data support advancing programs in

cold agglutinin disease (CAD) and C3 glomerulopathy (C3G)

CAD

Cold Agglutinin Disease

• Chronic anemia
• Driven by extravascular hemolysis (Ig-M)
• No approved therapies
• ~12,000 patients in US, Europe1

APL2-CP-AIHA-208; NCT032266782

Interim Results: PLAUDIT Study

168 days of treatment

C3 Glomerulopathy

Interim Results: DISCOVERY Study

normal

C3G

• 50% end stage renal disease within 5-10 years
• ~85% transplant recurrence
• No approved therapies

• ~7,000 patients in US, Europe4	48.23% reduction
	in uPCR from
	baseline observed

APL2-201; NCT034536193

Sources: 1. Berentsen S, et al. Haematologica. 2006; 91(4):460-466. 2. Fattizzo B, et al. European Hematology Association. June 13-16, 2019. Sources: 3. Dixon BP et al. American	20
Society of Nephrology (ASN) Kidney Week, Nov 5-10, 2019, Washington DC. FR-PO906. 4. ClearView Analysis using physician and literature consensus.

Intravitreal pegcetacoplan:

GEOGRAPHIC

ATROPHY (GA)

Geographic Atrophy (GA)

Intermediate AMD

Presence of drusen.

No serious vision loss.

GA

Wet AMD

Geographic Atrophy

Rapid, serious vision loss if untreated.

First-line treatment with VEGF inhibitors. Up to 98% of chronic

anti-VEGF patients progress to GA.

Risk of blindness when central vision

is affected. ~1 million patients in US

alone. No approved therapies.

Source: American Academy of Ophthalmology; The Lancet; Ophthalmology; L.E.K. interviews and analysis

22

Phase 2 FILLY trial: Design

GA

Sham group

N=81 (pooled)

pegcetacoplan

N=79

pegcetacoplan

N=86

Primary endpoint read out

							No study drug administered
							from Month 12 to 18
	1 year			6 mo.

pegcetacoplan:

0 mg sham injections

pegcetacoplan:

15 mg/0.1 mL every other month

pegcetacoplan:

15 mg/0.1 mL monthly

Population: patients with

Geographic Atrophy* secondary to AMD

Design: single masked, randomized 2:1:2:1

Treatment: 15 mg/0.1 mL intravitreal injection vs. Sham injection.

Sample size: 246 subjects at 46 sites#

Duration: 18 months

* Confirmed by the central reading center using FAF images	Liao, D et al. Ophthalmology. 2019. pii: S0161-6420(18)33132-4. [Epub ahead of	23
# Not counting the 3 satellite sites	print]

Protocol study number, POT-CP121614 (FILLY); NCT02503332

Phase 2 FILLY trial: Timeline and endpoints

GA

images
taken at
	2	6	12	18
0
				months	months	months	months

treatment	no
period	injections

Primary efficacy endpoint

Change in geographic atrophy (GA) lesion size from baseline at month 12

Primary safety endpoint

Number and severity of local and systemic treatment emergent adverse events (TEAEs)

POT-CP121614, NCT02503332

24

Pegcetacoplan slowed GA growth* at 12 months

				sham	pegcetacoplan	pegcetacoplan
				injections	every other month	monthly
				(N=80)	(n=78)	(N=84)
			0.4
	in
	Baseline	(mm)				0.35
	0.3				20%
					†
GA	fromChange(±SE)Mean	LesionGARootSquare				0.28*
			0.25	29%
			0.2
						* p=0.067 vs Sham
						† p=0.008 vs Sham
			0.1
	LS
			0	2
			0	6	12

Change from baseline in square root		Sham	Lampalizumab, 10mg
of GA area at 48 wk, mm
	Pooled (n=598)	Q4w (n=596)	Q6w (n=603)
	population				25
Adjusted mean (SE)	0.342 (0.007)	0.349 (0.007)	0.352 (0.007)
				Protocol study number, POT-	CP121614 (FILLY); NCT02503332

Mean change from baseline to month 12*

Observed data

		sham		pegcetacoplan	pegcetacoplan
		injections		every other month	monthly
		(N=80)		(n=78)	(N=84)
	Squarein	0.4
				0.361
	Baselinefrom Lesion(mm)	0.3			0.272*	25%
GA
			0.246†	32%
	Change(±SE) RootGA	0.2
				* p = 0.021 vs Sham
					† p = 0.003 vs Sham
		0.1
	Mean	0
		0	2	6	12
				Month

Pegcetacoplan Monthly (n)	79	68	65
Pegcetacoplan EOM (n)	75	68	58
Sham Pooled (n)	77	72	66

*Square root. Modified intention-to-treat (mITT) population was used for the efficacy analysis. Observed, ANOVA at Month 12. p-values vs Sham are	Data on file	26
adjusted for multiplicity by the LSD method in a one-way ANOVA on results at Month 12. The model had an overall p-value of 0.006 for treatment

difference	Protocol study number, POT-CP121614 (FILLY); NCT02503332

GA lesion growth from baseline to month 18

				sham		pegcetacoplan	pegcetacoplan
				injections		every other month	monthly
			0.6	(N=80)		(n=78)	(N=84)
	Root GA		0.5					0.49
	inSquare
		0.4					0.41*	16%
	Baseline	(mm)					0.39 †
GA				0.35			20%
	fromChange	Lesion	0.3			0.28
						0.26
	(±SE)		0.2
							* p=0.097 vs Sham
	MeanLS							† p=0.044 vs Sham
		0.1
			0
			0	2	6	12	Off Treatment	18
						Month

*Square root. Modified intention-to-treat (mITT) population was used for the efficacy analysis; defined as all patients who received at least 1 injection and underwent at least 1 follow-up examination at month 2 or later at which primary efficacy data were collected. 2-sided t tests at the alpha = 0.1 level

Liao, D et al. Ophthalmology. 2019. pii: S0161-6420(18)33132-4	27
Protocol study number, POT-CP121614 (FILLY); NCT02503332

GA growth comparison: Fellow eye vs study eye post-hoc analysis

GA	Change from baseline in square root GA lesion growth (mm)

sham injections

(N=72)

0.4			0.4
0.3	Fellow		0.3
0.2	eye		0.2
0.1		Study	0.1
		eye
0			0
2 months	6 months	12 months

	pegcetacoplan
	every other month
	(n=63)
		10%
		Difference	0.4
		p > 0.1
	Fellow		0.3
	eye		0.2
		Study	0.1
		eye
			0
2 months	6 months	12 months

	pegcetacoplan
	monthly
	(N=69)
		23%
		Difference
		p = 0.083
	Fellow
	eye
		Study
		eye
2 months	6 months	12 months

Includes patients from the Bilateral GA Population

Data on file

28

GA

New-onset exudative AMD investigator-diagnosed through month 18

	Pegcetacoplan	Pegcetacoplan	Sham Pooled
	(APL-2) Monthly	(APL-2) EOM
All Subjects	n = 86	n =79	n = 81
Subjects with exudative AMD in Study eye	18	7	1
With History of CNV in Fellow Eye
Subjects with exudative AMD in Study eye	12/36 (33%)	5/28 (18%)	0/29 (0%)
No CNV History in Fellow Eye
Subjects with exudative AMD in Study eye	6/50 (12%)	2/51 (4%)	1/52 (2%)

Liao DS, Grossi FV, El Mehdi D, et al. Complement C3 Inhibitor Pegcetacoplan for Geographic Atrophy Secondary to Age-Related Macular Degeneration:

A Randomized Phase 2 Trial. Ophthalmology. 2019 pii: S0161-6420(18)33132-4.

29

GA

Pegcetacoplan (APL-2) reduced GA lesion growth in FILLY

Dose response

Increased effect over time

Contralateral and between groups

Sham group as expected

Modeled data consistent with observed data

• 26 FILLY subjects (11%) had exudations (18 monthly, 7 every-other-month, 1 sham)
• • CNV exudations
  • 0 cases of classical CNV
  • No impact on vision
  • FILLY Hypothesis: Pegcetacoplan may increase leakiness of pre-existing type 1 CNV

30

Derby & Oaks: Two Phase 3 clinical trials with 600 patients each

GA

Sham group

N=200 (pooled)

pegcetacoplan

N=200

pegcetacoplan

N=200

Primary endpoint read out

	1 year				1 year

pegcetacoplan:

0 mg sham injections

pegcetacoplan:

15 mg/0.1 mL every other month

pegcetacoplan:

15 mg/0.1 mL monthly

Population: patients with

Geographic Atrophy secondary to AMD

Primary endpoint: change in total area of GA lesion(s) based on Fundus Autofluorescence (FAF) at month 12

Design: double masked, randomized 2:1:2:1

Treatment: 15 mg/0.1 mL intravitreal injection vs. Sham injection.

Sample size: 600 subjects from approx. 100 multinational sites per study

Duration: 2 years

31

APL-9

Developing APL-9 for rapid C3 control in acute complement-mediated diseases

Product	Category		Disease	Pre-clinical	Phase 1	Phase 1b/2	Phase 3	Approved
		PNH	Paroxysmal Nocturnal
		Hemoglobinuria
	Hematology
Subcutaneous		CAD	Cold Agglutinin
pegcetacoplan		Disease
(APL-2)
	Nephrology	C3G	С3
	Glomerulopathy
Intravitreal	Ophthalmology	GA	Geographic
pegcetacoplan	Atrophy
Intravenous		AAVs	Control of Host
Gene therapy	Attack on AAVs for
APL-9
		Gene Therapies

32

Developing APL-9 to improve safety and efficacy in gene therapies

Innate immune system(hours)		Adaptive immune system(days)
1	3	4
C3b
C3b	C3b

APL-9

AAV opsonization	AAV	Indirect activation of	Indirect - NAB Formation
by C3b	phagocytosis	adaptive immune system	preventing re-treatment
	2
	C3b
	C3b
	C3b

Reduced

transduction33 efficiency

APL-9: Enhanced transduction efficiency

APL-9

Relative transduction

2.0				0 µM

10 µM APL-9 100 µM APL-9

1.5

1.0
0.5
0.0
1/ 20	1/40	1/ 80

Serum dilution

Experimental method:

• preincubated viralparticles in serum with low and high dose of APL-9 before conducting transduction assay
• AAV3b vector with lacZ reporter protein delivered to HuH7 cells
• relative transduction normalized to APL-9 100 µM

34

Apellis 2020: The future unlocked

PNH:

• Meet with regulators in H1 2020

• Present full 16-week PEGASUS data

• 48-weektop-line PEGASUS data
• Provide update on Phase 3 PRINCE trial Complete enrollment of Phase 3 GA studies Advance pegcetacoplan in C3G and CAD Progress APL-9 in gene therapies

35

THANK YOU

PIONEERING

TARGETED C3 THERAPIES

March 4, 2020