Portola

Pharmaceuticals
January 2017
 Forward-Looking Statements

This presentation contains forward-looking statements within the meaning of the

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statements by forward-looking words, such as believe, may, will, estimate,
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These forward-looking statements are subject to a number of risks, uncertainties and

assumptions, and new risks emerge from time to time. In light of these risks,
uncertainties and assumptions, the forward-looking events and circumstances
discussed in this presentation may not occur and actual results could differ materially
and adversely from those anticipated or implied in the forward-looking statements.
Please refer to our Annual Report on Form 10-K and our most recent Quarterly Report
on Form 10-Q that we filed with the SEC for a description of risks and uncertainties that
could impact future results.

Although we believe that the expectations reflected in the forward-looking statements

are reasonable, we cannot guarantee that the future results, levels of activity,
performance or events and circumstances reflected in the forward-looking statements
will be achieved or occur. We undertake no obligation to update any forward-looking
statements except as required by law.

2
 Pipeline: Approval-stage Breakthrough and Fast Track
Products in Areas of High Unmet Medical Need

OWNERSHIP FDA/ EMA

THROMBOSIS/HEMATOLOGY RIGHTS
PHASE 1 PHASE 2 PHASE 3
Review

Betrixaban
Anticoagulant oral, FXa inhibitor
Hospital and extended-duration VTE 100% FAST TRACK PRIORITY REVIEW
PDUFA June 24, 2017
Px in high-risk AMI patients

100% ex-Japan BREAKTHROUGH

Clinical collaborators

Antidote for FXa inhibitors Japan

Cerdulatinib
100%
Relapsed and refractory hematologic
cancers

3
 Significant Upcoming Milestones & Catalysts
Robust Thrombosis Franchise with Potential FDA & EMA Regulatory Approvals

Betrixaban Timing Event

Q2 2017* Advisory Committee
June 24th PDUFA
~Aug 2017 US Launch**
Q4 2017 CHMP Opinion
Q1 2018 EMA Approval

Timing Event
Q2 2017 BLA Re-Submission
Q4 2017 CHMP Opinion
YE 2017 FDA Approval (Gen 1)
Q1 2018 EMA Approval (Gen 1)
1H 2018 FDA Supplemental Approval (Gen 2)
1H 2018 EMA Supplemental Approval (Gen 2)

4 *Date not yet determined

** Assuming approval
 Betrixaban and AndexXaTM Target Multi-Billion Dollar
Markets Where No Drugs Approved/Limited Options
Current NOAC Indications
SPAF >$5B betrixaban
20 ACS &
VTE Tx
VTE Px Orthopedic Surgery addressable market
$15.6B*
15
VTE Px Acute
$3-4B Medically ill
$10B*
$ BILLIONS

10
Anticoagulant
$2B antidote

2012 2013 2014 2015 2016 2017 2018 2019 2020

5 Sources: *Evaluate Pharma January 2017; Portola estimates

 Urgent Need to Address Preventable Deaths from VTE
Acute Medically Ill: Hospitalized Patients with Heart Failure, Stroke, Infection,
Pulmonary & Rheumatic Disease

>24 Million
Acute medical patients
indicated for VTE prevention (G7)

>1 Million
will suffer a blood clot within
35 days

150,000
estimated to survive condition but 41 year old, acute
die of VTE every year medically ill patient
2021 projected In G7 countries
6 Source: Worldwide annual acute medically ill patients that survive their medical condition but die of VTE AHA Heart and Stroke Statistics, 2011; HCUP data 2009, Nf TMH et al Circ Heart Failure 2010;
3;165-173; Kelly, Stroke 2001;32:262-267; COPD International, Tapson, VF Proc Am Thorac Soc April 1, 2005 vol 2 no. 1 71-77; CDC website, Levine, R. Chest 2003 124: Navigant Analysis
 Betrixabans Unique Properties to Reduce VTE without
Increasing the Rate of Major Bleeding

Once-daily half life

Lowest renal clearance
Not metabolized by CYP3A4
(Commonly used CYP3A4 inhibitors e.g., clarithromycin, erythromycin, HIV
protease inhibitors, fluconazole, itraconazole)

BETRIXABAN RIVAROXABAN APIXABAN EDOXABAN ENOXAPARIN

Half Life 19-25 hrs* 5-9 hrs 9-13 hrs 8-10 hrs 4.5-7 hrs

Renal
5-7% 36% 25% 28% >40%
Excretion
CYP3A4
No Yes Yes No No
Interactions

7 *Betrixabans pharmacological half life

 APEX Study Design: Hospital & Extended Duration
Betrixaban Compared to Standard Duration Enoxaparin

Enrollment: 7,513 patients

Primary End
Day Point: Day
10 + 4 Day 35 - 42 65 - 70
Safety
Ultrasound follow-up visit
Hospitalization
Age 75 Enoxaparin Placebo
D-dimer
Multiple risk
factors
R Primary endpoint: Composite of VTE-related death,
1:1 randomization
non-fatal PE, proximal DVT (by U/S), or symptomatic DVT
Betrixaban Betrixaban

8
 Primary Efficacy and Safety Results: Portola Analysis
Local D-Dimer Lab, 80mg & 40mg doses

Cohort 1 Cohort 2 Overall Study

D-dimer 2 ULN D-dimer or Age >75 Population

12 p=0.054 p=0.029 p=0.006

RRR 19.4% RRR 20.0% RRR 24.0%

8.5%
6.9% 7.1%
VTE Events

7.0%
6 5.6% 5.3%
Incidence (%)

0
0.7%
Major Bleeding

0.6% 0.7% 0.6% 0.6% 0.7%

2 p=0.72 p=0.56 p=0.55
Enoxaparin Betrixaban Enoxaparin Betrixaban Enoxaparin Betrixaban
N =1956 N =1914 N = 2893 N = 2842 N = 3174 N = 3112

N = 3870 N = 5735 N = 6286

Gibson et. al. ISTH SSC 2016 May 27, 2016

9
 Primary Efficacy and Safety Results: APEX Academic
Researchers Analysis
Local D-Dimer Lab, 80mg & 40mg doses

Cohort 1 Cohort 2 Overall Study

Academic Analysis Population

12 p=0.048 p=0.025 p=0.005

RRR 19.8% RRR 20.3% RRR 24.3%

8.5%
6.9% 7.1% 7.1%
VTE Events

6 5.6% 5.3%
Incidence (%)

0
0.46% 0.52% 0.6% 0.7%
Major Bleeding

0.6% 0.7%
2 p=0.78 p=0.56 p=0.55
Enoxaparin Betrixaban Enoxaparin Betrixaban Enoxaparin Betrixaban
N = 1957 N = 1914 N = 2894 N = 2842 N = 3175 N = 3112

N = 3871 N = 5736 N = 6287

Gibson et. al. ISTH SSC 2016 May 27, 2016

10
 APEX: Results by Dose Administered

80 mg Dose 40 mg Dose
12 p=0.001 p=0.836
RRR 30.3% RRR -0.5%

7.2%
6.7% 7.0%
VTE Events

6 5.0%
Incidence (%)

0
0.6% 0.7%
Major Bleeding

0.6% 1.4%
2
p=0.96 p=0.20
Enoxaparin Betrixaban Enoxaparin Betrixaban
N = 2562 N = 2506 N=609 N=603

N = 5068 N = 1212

Gibson et. al. ISTH SSC 2016 May 27, 2016

11
 Symptomatic VTE Outcomes Through Day 35 and
End of Study (80mg & 40mg Doses by Local Lab)

Composite of Symptomatic Proximal or Distal DVT, Non-Fatal PE, or VTE-related Death

Cohort 1 All Patients Randomized

3.0 Through Visit 3 3.0 Through Visit 3
HR = 0.70 (0.44, 1.11) HR = 0.65 (0.42, 0.99)
ARR = 0.68% 2.61% ARR = 0.51%
Probability of Symptomatic Event (%)

Probability of Symptomatic Event (%)

NNT = 147 NNT = 196
2.25%
2.5 2.5

1.84%
p=0.03
2.0 p=0.12 2.0 1.44%
Enoxaparin
1.5 1.5 p=0.004
Enoxaparin
1.57% p=0.043
Parenteral
Therapy
1.57% Parenteral
Therapy

1.0 1.0 1.04%

0.93%
Through End of Trial* Through End of Trial*
HR = 0.60 (0.38, 0.94) HR = 0.56 (0.38, 0.84)
Betrixaban

Visit 3
Visit 3

0.5 ARR = 1.04% 0.5 ARR = 0.80%

NNT = 96 Betrixaban NNT = 125

0 0
0 5 10 15 20 25 30 35 40 45 50 55 60 65 70 75 0 5 10 15 20 25 30 35 40 45 50 55 60 65 70 75
Time (Days) Time (Days)
E 1956 1943 1933 1928 1902 1889 1882 998 E 3753 3633 3561 3533 3485 3446 3432 1836
B 1914 1904 1898 1895 1869 1853 1845 947 B 3759 3637 3573 3548 3496 3453 3432 1802

*End of Trial defined as final follow-up visit (30 + 5 days after Visit 3)
12 Gibson et. al. ISTH SSC 2016 May 27, 2016
 1
Fatal or Irreversible Outcomes Net Clinical Benefit 3
All Patients Randomized
Non-hemorrhage cardiopulmonary death + Non-fatal PE + MI + ischemic
stroke + Fatal bleeding + ICH

Through Visit 3
HR = 0.71 (95% CI: 0.56, 0.91)
ARR = 1.18%
NNT = 85 5.17%
4.08%
p = 0.002
Enoxaparin p = 0.006
3.64%
2.90%
Through End of Trial*

visit 3
HR = 0.70 (95% CI: 0.57, 0.88)
Betrixaban
ARR = 1.53%
NNT = 65

*End of Trial defined as final follow-up visit (30 + 5 days after Visit 3)
*End of Trial defined as final follow-up visit (30 + 5 days after Visit 3)
13
Gibson et. al. ISTH SSC 2016 May 27, 2016
 Betrixaban Can Expand $2.7B Addressable Market to $3-4B
in G7
Reduction in VTE w/o Increase in Major Bleeds vs. SOC and Extending Length of Therapy

Injectables
G7 Acute Medical Hospital Stays (millions) 24M patients
6 days of therapy
55% adoption
~$2.7B peak market

28.4
26.6
Betrixaban
24.0
16M patients
35 days of therapy
2015 2021 2025 Parity pricing to oral FXas
$3-4B+ addressable market*

*Source: Decision Resources

14
 FXa Inhibitor Hospital Admissions Due to Bleeding is
Increasing and is Associated with Increased Death

~80,000 annual US hospital admissions for

Hospital Admissions direct oral FXa inhibitor bleeding1
for FXa-i Major Bleeds or Urgent Surgery
1,000
1,000
Expected to grow to >500,000 admission
Thousands of Patients

for major bleeding or urgent surgery

Thousands of Patients

in G7 by 2020 (70% novel Xa)

500500

Bleeding patient outcomes

Mortality: 15% at 30 days2
>40% mortality in large Phase 3 trials
00
Morbidity: LOS = 8 days3
2012 2016 2020 2024 2028 2032 Cost: top 15% > $100K
US EU/JP

>$2B AndexXa Market Opportunity

Sources: IMS MIDAS; EvaluatePharma; Navigant analysis; Truven; Portola estimate
1. Truven, MarketScan Commercial, Medicare Supplemental, last 12 months ending Dec 31,2015. Medicaid accounts for ~5% of the total bleed related admissions
2. The data for mortality from major bleeds ranges from 5.1% (DRESDEN Registry) to 33% (RIETE Registry). Other data such as the ARISTOTLE trial (Granger et al, NEJM 2011) suggest 11 15%
15 3. LOS = The LOS in the Truven report varies by payor. In the YTD 10/2014 report the LOS were 8.0 (12.0), 7.1(9.3) for Commercial, Medicare respectively.
 PCCs Lack Both Scientific Rationale and Clinical Data
that Demonstrates Ability to Reverse Xa Inhibitors

PCC vs. Saline to Reverse Rivaroxaban Xa Activity

4F-PCCs effectively reverse warfarin

4F-PCCs do not reverse Factor Xa Kcentra PCC (n = 12)

Saline (n = 12)
inhibitors as measured by anti-factor
Xa activity or plasma concentration

Labeled amount of FX in 4F PCC

products is ~ 0.2%-1.2% of whats
needed to reverse FXa inhibitor

No well controlled data or ongoing

label enabling study in FXa inhibitor
bleeding patients

Levi et al, J Thromb Haemost 2014

16
* Data on file
 AndexXa Has Potential to be the First and Only Antidote
to Reverse FXa Inhibitors
Only agent to reduce anti-
FXa activity in clinical trials Confirmatory trial in
Only agent that binds of healthy volunteers bleeding patients is
directly to FXa inhibitors
ongoing

Ideal for hospital setting

Immediate onset
Sustained infusion reversal
Short half-life
17 Andexanet alfa is an investigational product that has not yet been approved for use
 Phase 3b/4 Confirmatory Study in Patients with Acute
Major Bleeding

AndexXa

Up to 350 pts with life 30 day safety

threatening bleeding 12hrs follow up

>160 patients 1. Anti-Xa 2. Hemostasis

currently enrolled
in US and EU Co-primary efficacy endpoints

Low Dose High Dose

Andexanet IV bolus and 2 hour infusion

18
 Interim Results: AndexXa Rapidly Decreases Apixaban
Anti-FXa Activity

Apixaban: Bolus +Infusion

Anti-FXa [median, 25th, 75th percentiles, N=20]

End of End of
bolus infusion
Apixaban (N=20)
200
Anti-Factor Xa (ng/ml)

150

100

50

0
0.0 0.2 0.4 0.6 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15
Time since Bolus (hrs)

19 Connolly NEJM 2016, 10.1056/NEJMoa1607887

 Clinical Hemostatic Efficacy Interim Results

No of
Adjudicated Excellent or Good Hemostasis (95% Cl)
Patients

All adjudicated efficacy patients 47 80 (64-89)

Drug
Rivaroxaban 26 81 (61/93)
Apixaban 20 75 (51-91)
Enoxaparin 1 100
Sex
Male 24 71 (49-87)
Female 23 87 (66-97)
Site of bleeding
Gastrointestinal 25 84 (64-96)
Intracranial 20 80 (56-94)
Other 2 0
Age
<65 yr 7 71 (29-96)
65-75 yr 9 89 (52-100)
75 yr 31 77 (59-90)
Andexanet dose
Low 42 76 (61-88)
High 5 100 (48-100)
Anti-factor Xa <75 ng/ml or <0.5 IU/ml 17 82 (57-96)

20
Percent
 ANNEXA-4 Update NEJM Letter December 22, 2016
Thrombotic Event and Re-Anticoagulation Rates

ANNEXA-4 ANNEXA-4
NEJM Publication NEJM Update
August 2016 December 2016
Patients 67 105
30 day thrombotic 17.9% 12.4%
event rate (12/67) (13/105)
Interval : 1/38 = 2.6%

Re-anticoagulation 27% 40%

rate (by day 30) (18/67) (42/105)
Interval : 24/38 = 63%

21 Connolly et al. NEJM 2016. 375: 1131; 2Connolly et al. NEJM 2016. 375; 2498
 Key Deliverables for FDA Re-submission

Drug Substance/ Drug Product

Additional process data & completion of supplementary validation

Analytical methods and primary reference standard

Clinical Assays
Additional assays, testing of archived clinical samples & inclusion in ANNEXA-4

Clinical Data & Protocols

22
 Cerdulatinib: A New Option for Resistant or Relapsed
Hematological Cancers and Other Diseases

CERDULATINIB Pro-Inflammatory
B-cell
Receptor Tumor Environment
Cytokines
IL-2, IL-4, IL-6, IL-10, TNF

Tumor Derived
Cytokines
PI3K IL-6, IL-10

Gilead
Pharmacyclics Incyte Jakafi
Zydelig
Infinity ImbruvicaTM
IPI-145

23
 Phase 1 Dose Escalation Study Investigator Assessed
Best Change in Tumor Size

100%

CLL/SLL FL MCL DLBCL Transformed FL

80%

60%

40%

20%

0%

(20%)

(40%)

(60%)
12 patients on drug > 200 days; 17 > 100 days;
3 patients currently on drug for > 1 year
(80%)

(100%)
All patients assessed to date all doses studied, n = 33

24
 Cerdulatinib Safety Profile vs. Ibrutinib and Idelalisib in
Phase I Studies

Ibrutinib1 Idelalisib2 Cerdulatinib3

(N=56) (N=64) (N=43)

Patients d/c due to 11% 20% 7%

AEs

Grade 3+ AEs
Neutropenia 13% 23% 7%
ALT increase 0% 23% 0%
Diarrhea 4% 9% 9%
AST increase 0% 20% 2%
Fatigue 4% 3% 14%
Thrombocytopenia 7% 11% 2%
Anemia 7% 5% 12%
Bleeding 0% 0% 0%

1 Advani JCO 2013 (phase 1)

25 2 Flinn Blood 2014 (phase 1)
3 cerdulatinib ASCO 2016
 Capitalized to Fund Projected Development Milestones
$274.6 M Cash, Cash Equivalents & Investments (9/30), additional $50 M loan from
BMS/Pfizer (12/16)
2017 2018
2016 2017
US Milestones

Advisory PDUFA Launch*

Committee 20156/24/17
Approval
Betrixaban

EU
approval
EU Milestones

CHMP EMA Q3
Opinion Approval
US Milestones

BLA Re- FDA Launch* FDA

Submission Approval Supplemental
(Gen 1) Approval
Andexanet

(Gen 2)
EU Milestones

CHMP4 ongoing EMA

Phase
Opinion Approval

EMA Supplemental
Approval (Gen 2)

Phase 4 Ongoing
26 *Assuming approval
NASDAQ: PTLA