Alector : Corporate Presentation November 2020

November 2020

Harnessing the Immune System to Cure Neurodegeneration

Confidential

Forward Looking Statements

This presentation contains forward-looking statements that involve substantial risks and uncertainties. All statements other than statements of historical facts contained in this presentation, including statements regarding our future financial condition, results of operations, business strategy and plans, and objectives of management for future operations, as well as statements regarding industry trends, are forward-looking statements. In some cases, you can identify forward-looking statements by terminology such as "anticipate," "believe," "continue," "could," "estimate," "expect," "intend," "may," "plan," "potentially" "predict," "should," "target," "will" or the negative of these terms or other similar expressions.

We have based these forward-looking statements largely on our current expectations and projections about future events and trends that we believe may affect our financial condition, results of operations, business strategy and financial needs. These forward-looking statements are subject to a number of risks, uncertainties and assumptions, including, among other things: the ability of our clinical trials to demonstrate safety and efficacy of our product candidates, and other positive results; the timing and focus of our future clinical trials, and the reporting of data from those trials; our plans relating to commercializing our product candidates, if approved; the expected potential benefits of strategic collaborations with third parties and our ability to attract collaborators with development, regulatory and commercialization expertise; our estimates of the number of patients who suffer from the diseases we are targeting; our ability to expand our product candidates into additional indications and patient populations; the beneficial characteristics, safety, efficacy, and therapeutic effects of our product candidates; our plans relating to the further development and manufacturing of our product candidates, including additional indications we may pursue; our continued reliance on third parties to conduct additional clinical trials of our product candidates, and for the manufacture of our product candidates for preclinical studies and trials; our plans and ability to obtain or protect intellectual property rights; the accuracy of our estimates regarding expenses, future revenue, capital requirements, and needs for additional financing; our financial performance; and the sufficiency of our existing cash and cash equivalents to fund our future operating expenses and capital expenditure requirements. These risks are not exhaustive. New risk factors emerge from time to time and it is not possible for our management to predict all risk factors, nor can we assess the impact of all factors on our business or the extent to which any factor, or combination of factors, may cause actual results to differ materially from those contained in, or implied by, any forward-looking statements, as discussed in greater detail in our filings with the Securities and Exchange Commission (SEC), including without limitation in our Quarterly Report on Form 10-Q, as filed on November 10, 2020 with the Securities and Exchange Commission ("SEC"). You should not rely upon forward-looking statements as predictions of future events. Although we believe that the expectations reflected in the forward- looking statements are reasonable, we cannot guarantee future results, levels of activity, performance or achievements. Except as required by law, we undertake no obligation to update publicly any forward-looking statements for any reason after the date of this presentation.

In addition, statements that "we believe" and similar statements reflect our beliefs and opinions on the relevant subject. These statements are based upon information available to us as of the date of this presentation, and while we believe such information forms a reasonable basis for such statements, such information may be limited or incomplete, and our statements should not be read to indicate that we have conducted an exhaustive inquiry into, or review of, all potentially available relevant information. These statements are inherently uncertain and investors are cautioned not to unduly rely upon these statements.

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Pioneering immuno-neurology

	IMMUNO NEUROLOGY
	Recruiting the brain's immune system
	to cure neurodegeneration
Our therapeutics			Genetically defined
are genetically validated			patient populations and
regulators of the brain's			biomarkers enhance
immune system			probability of success

Human Genetics

Immunology

Neuroscience

3

Human genetics has enabled a new therapeutic strategy

22/29

of AD risk genes are microglia specific (red)

Disease association

Annotated from Nature Genetics 2019 Mar;51(3):404-413

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Our differentiated approach: Combining human genetics with our understanding of immunology and neurodegeneration

Our therapies are designed to restore the function of the microglia to treat these multiple parallel pathologies in order to slow or stop the progression of neurodegenerative disease

Antibody

Alector's

Immuno-Neurology

Approach

Provide nourishing factors

Remove pathological proteins

Maintain synapses

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Rapidly translating scientific leadership into emerging portfolio of first-in-class programs

Multiple first- in-class clinical programs

Robust discovery pipeline

• Advanced 4 candidates into the clinic since our founding
• Advanced AL001 from preclinical to a Ph 3 study in less than two years
• Two immuno-neurology programs for Alzheimer's disease, advancing to Ph 2
• 3 additional clinical ready programs progressing forward
• >120 immune system targets
• Progressed 14 programs into R&D development
• >200 patent applications, 38 patent families and 6 issued U.S. patents

Current cash and equivalents of $461.7M* expected to fund operations through 2022

*As of 3Q 2020	6
** FIH: first-in-human trials

Robust portfolio of product candidates targeting the innate immune system

PRO G RAM	C AN DI DATE	RESEARCH	PRE-C L I N I CAL	PHASE 1	PHASE 2	PHASE 3	PARTNER
	AL001	FTD-GRN
Progranulin	AL001	FTD-C9orf72
	AL101	Neurology
TREM2	AL002	Alzheimer's disease (AD)
SIGLEC3	AL003	Alzheimer's disease (AD)
MS4A4A	AL014	Alzheimer's disease (AD)
SIRP-alpha	AL008	Cancer
Multi-Siglec	ADP009	Cancer
Research pipeline	ADP012
	ADP016
	ADP017
	ADP023
	ADP026
	ADP122
	ADP022

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Portfolio optimized for enhanced clinical success

Each development program incorporates:

	!
Proven, genetically				Defined patient
Biomarkers
validated targets
			populations

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FTD-GRN represents our initial indication from our first-in-class progranulin program

MRI of frontal and temporal atrophy in FTD

• Frontotemporal dementia (FTD) is a devastating and rapidly progressive form of dementia
• Early onset under the age of 60
• Life expectancy 7 - 10 years
• 170,000 FTD patients in (US + EU)
  − 15,000 patients with PGRN mutations (FTD-GRN)

Image source: Brain, Volume 129, Issue 11, 1 November 2006, Pages 3103-3114.	9
Note: Arrows added to MRI image of brain pointing to enlarged ventricles, a sign of brain atrophy.

AL001 scientific rationale: PGRN deficiency causal for FTD

Homozygous mutations (100% LOF)

• 100% decrease in PGRN levels
• Dementia, vision loss, epilepsy, death1

Heterozygous mutations (50% LOF)

• >50% decrease in PGRN levels
• FTD with >90% penetrance
• Dementia, death within 7 - 10 years

Regulatory mutations (~20% LOF)

• ~20% decrease in PGRN levels
• Risk factor for Alzheimer's3, Parkinson's diseases3

Note: LOF - loss of function.

1. Sci Transl Med. 2017 Apr 12;9(385)
2. Dement Geriatr Cogn Disord Extra 2016;6:330-340;
3. Eur J Neurol. 2013 Dec;20(12):1571-3; Gene. 2014 Jun 1;542(2):141-5

Plasma2	Cerebrospinal fluid (CSF)2
	10

AL001 for FTD-GRN: Targeting progranulin to restore function of microglia

MECHANISM OF ACTION

• Increases the half-life of PGRN by blocking Sortilin, a degradation receptor, in order to restore PGRN to normal levels

PGRN

PGRN

PHASE 1/2 DATA

• AL001 was safe and well tolerated in healthy volunteers and patients and showed target engagement and restoration of
  PGRN

STATUS

• Pivotal Phase 3 study initiated in July 2020

REGULATORY

• Orphan Drug and Fast Track Designation

PGRNPGRN

Degradation Pathway (Sort1)	AL001
Degradation Pathway (Sort1)

PGRN

degradation

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AL001 Phase 1 study design

In the Phase 1 study, AL001 was generally safe and well tolerated with no SAEs or DLTs reported

Phase 1a Dose Escalation (N = 50)

Healthy Volunteers	AL001 dose escalation	N = 50
1 dose

STUDY OBJECTIVES: Safety and tolerability, Pharmacokinetic (PK), and pharmacodynamic (PD) markers in blood and CSF

Phase 1b Open Label (N = 14)

Asymptomatic FTD-GRN	AL001 60 mg/kg	N = 6
1 dose
Symptomatic FTD-GRN	AL001 30 mg/kg	N = 8
q2w x 3 doses

PRIMARY ENDPOINT: Safety and tolerability

SECONDARY ENDPOINT: Pharmacokinetic (PK)

EXPLORATORY: Pharmacodynamic (PD) markers in blood and CSF

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AL001 increased plasma progranulin in healthy volunteers

AL001 was generally safe and well tolerated

AL001 triples PGRN levels in plasma

N = 50

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Phase 1 data shows AL001 restores PGRN levels back to the normal range

CSF Progranulin Level (ng/ml)

Sustained increase in CSF PGRN in AL001 Phase 1b study

Pre-dose	Pre-dose	12 days	Pre-dose*	56 days
post-dose	post-dose

5

4

3

2

1

0

Healthy Volunteers (HV)	Asymptomatic (aFTD-GRN)	Symptomatic (FTD-GRN)
(N = 33)	Single dose (N = 6)	3 doses every 2 weeks (N = 8)

Individual dots represent individual subjects. Horizontal line represents the median.	14
* One symptomatic subject did not have a reportable CSF PGRN baseline level which complied with Core lab SOP and was therefore excluded.

AL001 counteracts disease protein signature by normalizing inflammatory and lysosomal biomarkers and demonstrates a decrease in NfL in Phase 1b

	AL001 reduced CSF			AL001 reduced CSF
	Osteopontin (SPP1),			Chitotriosidase (CHIT1),
	a marker of inflammation			a marker of gliosis
						52% decrease									22% decrease
	200%															400%
									*														*
	180%
(a.u.)														(a.u.)	350%
160%
													300%
levels
140%														levels
													250%
120%
relative	80%														relative	200%
	100%
SPP1CSF	60%														CHIT1CSF	150%
													100%
	40%
															50%
	20%
															0%
	0%
	HV Pre-	FTD	FTD +				HV Pre-	FTD	FTD +
		Dose	Baseline	AL001					Dose	Baseline	AL001

Note: * represents p<0.05

NfL = Neurofilament light chain

1 Alector Research and Development Day presentation, December 13, 2019 2 SEM: standard error of the mean

	AL001 increased CSF		Trend in reduction
Cathepsin B (CTSB), a marker	of plasma Neurofilament
	of lysosomal function	(NfL) levels from baseline in
		58% increase			Phase 1b1,2
	140%			levels	1.5
				1.4
levelsrelativeCSTBCSF(a.u.)	120%			NfLrelativemeanGeometricplasma	1.3
100%		*	1.2
	80%				1.1
				1.0
	60%				0.9
	40%				0.8
					0.7
	20%				0.6
	0%				0.5
	HV Pre-	FTD	FTD +		0	20	40	60	80	100
					Days
	Dose	Baseline	AL001
										15

AL001 Phase 1b participants had the option to rollover into Phase 2

Phase 1b Open Label

(N = 14)

		Participants could roll
		over to Phase 2
Asymptomatic FTD-GRN	N = 6	N = 5
Symptomatic FTD-GRN	N = 8	N = 7

Dosing

discontinued

Phase 2 Open Label

(expected enrollment up to N = 40)

		AAIC Dataset (N = 15)
	AL001 60 mg/kg
Asymptomatic FTD-GRN*	N = 5 (5: Ph 1b rollovers)
q4w for 96 weeks
Symptomatic FTD-GRN*	AL001 60 mg/kg	N = 10** (7: Ph 1b rollovers)
	q4w for 96 weeks	(3: New patients)
Symptomatic FTD-C9orf72	AL001 60 mg/kg	Enrollment on-going
q4w for 96 weeks

PRIMARY ENDPOINT: Safety and tolerability

SECONDARY ENDPOINT: PK

EXPLORATORY: PD markers in blood and CSF, volumetric MRI (vMRI), Clinical Outcome Assessments

* Asymptomatic and Symptomatic FTD-GRN enrollment closed.
** Due to COVID-19 mediated site closures, 2/10 patients missed a dose and biomarker evaluations.	16
Confidential

AL001 Phase 2: Generally safe and well tolerated in FTD-GRN participants

	aFTD-GRN	FTD-GRN	Total
	(N=5) | n (%)	(bvFTD and PPA)
	(N=10) | n (%)	(N=15)	| n (%)
Any TEAE	4 (80.0)	4 (40.0)	8 (53.3)
Any Severe TEAE	0	1* (10.0)	1*	(6.7)
Any Treatment-Related TEAE	1 (20.0)	0	1 (6.7)
Any Treated-Related Severe TEAE	0	0		0
Any SAE	0	1* (10.0)	1*	(6.7)
Any TEAE Leading to Study Drug Discontinuation	0	1* (10.0)	1*	(6.7)
Any TEAE Leading to Study Discontinuation	0	0		0

• One participant had an unrelated severe SAEs (deep venous thrombosis) with onset date ~7 weeks after the last dose that led to treatment discontinuation. All other TEAEs were mild in severity.

Data cut-off: 13 April 2020
Note: aFTD = asymptomatic carriers of a GRN mutation causative of FTD; bvFTD = behavioral variant FTD; PPA = primary progressive aphasia, TEAE = Treatment	17
Emergent Adverse Event

Phase 2 data shows plasma PGRN restored to normal in FTD-GRN participants

180

Normal range from healthy volunteers

*

Data cut-off:14-May 2020

SEM: standard error of the mean

Solid circles represent the mean and the dashed bars represent the standard error of the mean. *Due to COVID-19 mediated site closures, 2/10 patients missed a dose and biomarker evaluations.

Confidential	18

Six out of eight participants in Phase 2 showed a decrease in NfL at their last measured timepoint

Natural Log of Plasma Neurofilament Level Over Time

Symptomatic FTD-GRN (N=8*)

Patient 6

Neurofilament	Patient 1	Patient 8
		Patient 5
		Patient 7
Plasma	Patient 4	Patient 3
Log(N)
	Patient 2

Plasma NfL levels - Symptomatic FTD-GRN

(N=8*)

	Plasma NfL (pg/mL)
Patient	Baseline	Last Measured	% Change in NfL	Last Measured
Timepoint	from Baseline	Timepoint
1	82.9	39.9	(52%)	Day 29
2	11.2	8.0	(29%)	Day 200
3	22.9	16.4	(28%)	Day 85
4	19.8	15.8	(20%)	Day 58
5	68.0	64.8	(5%)	Day 122
6	148.8	141.2	(5%)	Day 85
7	46.3	55.1	19%	Day 122
8	39.7	76.1	92%	Day 117

Phase 2 data cut-off:14-May-2020	19
*Due to COVID-19 mediated site closures, 2/10 patients missed a dose and biomarker evaluations.

AL001 case study: 47yo FTD-GRN patient with primary progressive aphasia

197 days of uninterrupted dosing shows a decrease in NfL

• Patient enrolled and completed Phase 1b, PGRN levels normalized and NfL decreased
• Patient had a 137-day gap between last dose in Phase 1b and enrollment in Phase 2, during which NfL increased by 37%
• After being on drug for 197 days in the Phase 2, without interruption, patient's NfL decreased by 29%

137 Days - Dosing discontinued

Normal

PGRN range

-17%	+37%		-29%

57

85

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Plasma NfL levels : Neurofilament Light Chain

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AL001 program next steps

• FTD-C90rf72patients will continue the enrollment in Phase 2 (up to 20 total)
• Present additional data from the Phase 2 trial of AL001 in pre-symptomatic and symptomatic FTD-GRN participants and an additional cohort of FTD-C9orf72 patients in 2021
• Continue to execute INFRONT-3 pivotal Phase 3

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AL001 next steps: Pivotal Phase 3 study initiated in July 2020

Approximately 50 clinical centers, including GENFI and ALLFTD registry sites, will be included in the global Phase 3 study

Randomization	Study			Study
Treatment	Completion Visit
Randomized, Double Blinded, Placebo Controlled Study (N = 180)
Individuals at Risk for or with FTD -GRN	AL001 60 mg/kg	8 weeks F/U	Open label extension
IV q4w for up to 96 weeks

PRIMARY ENDPOINT: CDR® plus NACC FTLD-SB

SECONDARY CLINICAL ENDPOINT: CGI-S, CGI-I,FRS

BIOMARKER ENDPOINTS: vMRI, CSF, blood

CDR® plus NACC FTLD-SB = Clinical Dementia Rating Dementia Staging Instrument PLUS National Alzheimer's Disease Coordinating Center Frontotemporal Lobar
Degeneration Behavior and Language Domains Sum of Boxes; CGI-S = Clinician's Global Impression-Severity;CGI-I = Clinician's Global Impression-Improvement; FRS	22
= Frontotemporal Dementia Rating Scale

Targeting PGRN beyond FTD-GRN: Indication expansion

Causal

GENETIC EVIDENCE

	FTD-GRN		In Phase 3
	~15,000 Patients (U.S. & E.U.)
	FTD-C9ORF72		In Phase 2
	~15,000 Patients (U.S. & E.U.)
		ALS
		~48,000 Patients1 (U.S. & E.U.)
			All FTD
			~170,000 Patients (U.S. & E.U.)

AL001

• On-goingPhase 2 study includes FTD-C9orf72 cohort
• Additional indications include ALS and/or all FTD patients regardless of mutation

Positive Correlation

PD

~10M Patients (WW)

AL101

AD

>35M Patients (WW)

Note: Figure not to scale.

• Ongoing Phase 1 study assessing the safety and tolerability in healthy volunteers with data expected in 2021.

1. Nat Commun. 2016 Aug 11;7:12408.

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Alzheimer's disease represents a significant unmet need

No disease modifying therapeutics available

Most common

form of dementia1

60% to 70%

Initial onset in patients

over 652

~5.7 million2

cases in the U.S. in 2018 with projections to rise to nearly 14 million in 20502

6th3

leading cause of death in the U.S.

of all cases2

Past development programs focused on single pathology of disease, such as beta amyloid and tau proteins, which did not yield success.

1.	Wilson RS, Segawa E, Boyle, PA, Anagnos SE, Hizel LP, Bennett DA. The natural history of cognitive decline in Alzheimer's disease. Psychol Aging 2012;27(4):1008-17.
2.	Alzheimer's Association, "2018 Alzheimer's Disease Facts and Figures"[Alzheimer's Association]	24
3.	NIH National Institute of Aging, "Alzheimer's Disease Fact Sheet"

TREM2 has the strongest genetic links to Alzheimer's disease after only APOE4

Disease association

TREM2

• TREM2 homozygous loss of function may cause neurodegeneration by age 40, with a lifespan of ~10 years following diagnosis
• TREM2 heterozygous loss of function increases risk for AD by 3x
• A SNP (rs9381040) associated with increased TREM2 expression is protective against AD

Annotated from Nature Genetics 2019 Mar;51(3):404-413

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AL002 for AD: Targeting TREM2 to recruit microglia to counteract disease pathologies

MECHANISM OF ACTION

• Antibody designed to activate TREM2 and enhance microglia activity

PHASE 1 DATA

• AL002 successfully achieved its primary and secondary endpoints in the Phase 1 study

STATUS

• Initiating Phase 2 in 2020

PARTNER

• Global 50/50 profit and cost share partnership with AbbVie

AL002

TREM2

P P P P

Syk

Improve survival,

proliferation, function

of microglia

26

AL002 recruits microglia to counteract pathologies in AD mouse model

AL002 strongly increases a	AL002s recruit microglia	AL002s reduces area
marker of microglial proliferation	to plaques1	occupied by plaques1

proliferation marker

**** indicates a p-value < 0.0001 by T-test.	27
(1) Data generated by D. Wilcock, University of Kentucky

Target engagement and proof-of-mechanism in CSF achieved in Phase 1

AL002 was found to be generally safe and well-tolerated in 34 healthy volunteers

% change from baseline

Dose-dependent reduction

in soluble TREM2

N = 34* p < 0.001

Placebo		6 mg/kg		15 mg/kg		30 mg/kg		45 mg/kg		60 mg/kg

Dose-dependent elevation in sCSF-1R, associated with microglia activation

baselinefromchange%

N = 34*

*

p < 0.05

Placebo

6 mg/kg

15 mg/kg

30 mg/kg

45 mg/kg

60 mg/kg

28

AL002 next steps: Initiate Phase 2 in 2020

Patients

with

prodromal-

Randomization	Study	Study
Treatment	Completion Visit

Randomized, Double Blinded, Placebo Controlled Study* (48-96 weeks)

AL002 arms

8 weeks

to-mild

(early AD)

Placebo arm

PRIMARY ENDPOINT: CDR-SB

safety F/U

SECONDARY CLINICAL OUTCOME ASSESSMENTS:

RBANS, ADAS-Cog13,ADCS-ADL-MCI

* Number of active arms could change during the study	29

AL003 for AD: Increase activity of microglia by blocking SIGLEC 3

MECHANISM OF ACTION

• SIGLEC 3 is inhibitory receptor expressed on microglia
• AL003 blocks SIGLEC 3 in the same manner of a PD-1 inhibitor to allow immune system to work at fully capacity

PHASE 1A DATA

• AL003 successfully achieved its primary and secondary endpoints in the Phase 1a study

STATUS

• Phase 1b ongoing with data expected in 2021

PARTNER

• Global 50/50 profit and cost share partnership with AbbVie

Sialic acid

AL003

SIGLEC 3

Increases function by releasing

inhibition on microglia

30

SIGLEC 3 mutation a risk for Alzheimer's disease

SIGLEC 3 is an	Prevalent risk allele in AD*:
inhibitory receptor	•	Reduces ability to clear A beta	plaques**
for microglia	•	Leads to a smaller brain volume***

Protective SIGLEC 3 variant	Risk SIGLEC 3 variant
low A-beta	high A-beta

AA:	CC:			AA:	CC:
Protective	Risk Allele	Protective	Risk Allele
Allele				Allele

MFI SIGLEC 3

SIGLEC 3 Expression	A-beta clearance

*Neurobiol Aging. 2015 Apr;36(4):1765.e7-1765.e16.
**Nature Neuroscience volume 16, pages 848-850 (2013).	31
***Neurobiol Aging. 2015 Apr;36(4):1765.e7-1765.e16

Target engagement and proof-of-mechanism in CSF achieved in Phase 1a

AL003 was found to be generally safe and well-tolerated in 21 healthy volunteers

AL003 demonstrated long lasting peripheral target engagement

The Phase 1b portion of the study continues to enroll with data expected in 2021

32

Latest prioritized product candidates moving towards the clinic

AL014

for AD

• Designed to counteract the risk variants of MS4A4A and to functionally convert the risk variants of MS4A4A to the protective variant
• Goal: mimic and exceed the beneficial activity of the protective MS4A4A variant, which may potentially decrease the progression of AD
• First-in-humanstudy expected to initiate in the next 12-18 months

AL008

Oncology

ADP009

Oncology

• Novel antibody targeting the CD47-SIRP-alpha pathway
• Unique dual mechanism of action that relieves immune suppression (a "don't eat me signal") while also engaging Fc gamma to drive anti-tumor immunity
• First-in-classmulti-Siglec inhibitor that recruits innate immune cells to activate adaptive immunity

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In 2021, we will continue to advance Alector's broad clinical pipeline

AL001

AL002

AL003

AL101

AL014

• Continue progressing Phase 3 study of AL001 in FTD-GRN
• Phase 2 results in FTD-GRN
• Continue progressing Phase 2 study of AL002 in AD (initiation expected in 2020)
• Phase 1b results from AL003 in AD
• Phase 1 results of AL101 in healthy volunteers
• Initiation of Phase 1 FiH study of AL014

Current cash and equivalents of $461.7M*expected to fund operations through 2022

*As of 3Q 2020	34
** FIH: first-in-human trials

"At Alector we envision a world where dementia and neurodegeneration are illnesses of the past, just as smallpox and polio have become."

Arnon Rosenthal, PhD

Chief Executive Officer, Co-Founder

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November 2020

Harnessing the Immune System to Cure Neurodegeneration

Confidential

AL001 counteracts the disease protein signature in FTD patients in Phase 1b

GRN- FTD vs Healthy (Z-score)

Four-way rescue/phenocopy plot

CHIT1

SPP1

GRN

CTSB

AL001-treated vs Baseline GRN-FTD(Z-score)

• AL001 reduces inflammatory markers of disease (blue)
• AL001 increases proteins associated with lysosomal function (red)

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