BridgeBio Pharma : Company Presentation January 2020

C O M P A N Y P R E S E N T A T I O N

January 2020

Forward-Looking Statements

Statements in this Presentation that are not statements of historical fact are forward-looking statements. Such forward-looking statements include, without limitation, statements regarding our research and clinical development plans, expected manufacturing capabilities, strategy, regulatory matters, market size and opportunity, future financial position, future revenue, projected costs, prospects, plans, objectives of management, and the Company's ability to complete certain milestones. Words such as "believe," "anticipate," "plan," "expect," "intend," "will," "may," "goal," "potential" and similar expressions are intended to identify forward-looking statements, though not all forward-looking statements necessarily contain these identifying words. These forward-looking statements are based on the beliefs of the Company's management as well as assumptions made by and information currently available to the Company. Such statements reflect the current views of the Company with respect to future events and are subject to known and unknown risks, including business, regulatory, economic and competitive risks, uncertainties, contingencies and assumptions about the Company, including, without limitation, risks inherent in developing therapeutic products, future results from the Company's ongoing and planned preclinical studies and clinical trials, the Company's ability to obtain adequate financing to fund its preclinical studies and planned clinical trials and other expenses, trends in the industry, the legal and regulatory framework for the industry and future expenditures. In light of these risks and uncertainties, the events or circumstances referred to in the forward-looking statements may not occur. The actual results may vary from the anticipated results and the variations may be material. These forward-looking statements should not be taken as forecasts or promises nor should they be taken as implying any indication, assurance or guarantee that the assumptions on which such forward-looking statements have been made are correct or exhaustive or, in the case of the assumptions, fully stated in the Presentation. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date this Presentation is given. This Presentation discusses product candidates that are under preclinical study or clinical trial and which have not yet been approved for marketing by the U.S. Food and Drug Administration (the "FDA"). No representation is made as to the safety or effectiveness of these product candidates for the therapeutic use for which such product candidates are being studied.

Certain information contained in this Presentation relates to or is based on studies, publications, surveys and other data obtained from third-party sources and the Company's own internal estimates and research. While the Company believes these third-party sources to be reliable as of the date of this Presentation, it has not independently verified, and makes no representation as to the adequacy, fairness, accuracy or completeness of, any information obtained from third-party sources. In addition, all of the market data included in this Presentation involves a number of assumptions and limitations, and there can be no guarantee as to the accuracy or reliability of such assumptions. Finally, while the Company believes its own internal research is reliable, such research has not been verified by any independent source.

2

We are at Day 1 in the era of genetic medicine

Advances in science and medicine (2019)

• Better context: Cryptic genetic variation and modifiers
• Better understanding heterogeneity: genetic interaction manifolds and the wonderful story of Hirschsprung's Disease
• Deeper saturation: saturation genome editing
• Faster: Rapid whole-genome sequencing in the ICU
• Developing infrastructure: NHGRI reports cost per genome at $942 this year (all time low)
• Striking new therapeutics: SCD, CF, PN, TTR, SMA, and others

Source: Science, Science Translational Medicine, Nature, NEJM, NHGRI

Vast opportunity to help patients

6,650 7,000

350

Therapies	Diseases with	Known
today	no therapy	genetic
		diseases

3

We are building a leading genetic disease company

Core attributes…

1. Distinctive early stage asset selection
2. Experienced, product-focused R&D team
3. Efficient corporate structure
4. The willingness and scale to fail
5. Focus at the level of individual diseases and assets

…applied many times…

• 18 BridgeBio programs

…creating a pipeline of blockbusters and synthetic blockbusters

• Two $1B+ franchises in Phase 2 or later
• Two low risk NDAs being filed in this year
• Several early stage potential big franchises
• • KRAS
  • GPX4
  • Congenital adrenal hyperplasia
  • Leber's hereditary optic neuropathy
• Several low risk clinical or IND-enabling programs
• Four new programs announced in January 2020

4

BridgeBio is led by a world-class team of experienced drug developers

We rely on some of the top R&D minds in this industry to select assets…

Charles Homcy, MD

Chairman of Pharmaceuticals

Frank McCormick, PhD, FRS

Chairman of Oncology

Richard Scheller, PhD

Chairman of R&D

…and put them in the hands of one of the most productive groups of R&D operators in the industry

Uma Sinha, PhD

Chief Scientific Officer

Eli Wallace, PhD

Chief Scientific Officer in Residence, Oncology

Robert Zamboni, PhD

Chemistry

Tucatinib PT2997 (HER2i, Ph3) (HIF2αi, Ph3)

Together, our R&D team is responsible for 100+ INDs and 20+ approved products

5

Assessing BridgeBio

		Criteria		Relevance	Today's Talk
		High probability of success	• Historically higher probability of success for genetic	Current
		Pipeline
			disease drugs
	1
			Progress
		•	BridgeBio's early programs have outperformed
				historical probabilities

Number of programs

2

Capital efficiency

3

• We find great science and unlock its potential for patients
• Always searching for the next PellePharm or Eidos
• Scale allows for objective assessment and failure
• Generate value by making each program ROI-positive
• Driven by judicious use of capital at the high-risk preclinical stages

New

Programs

Spend to

IND

6

Genetic disease drug discovery is lower risk, faster, and has higher returns than traditional drug discovery

>4x Higher cumulative probability of success

Probability of success from Ph1 to

launch
50%		45%
40%
30%
20%
10%	10%
0%	Industry	Genetic
	average	average

Sources: Hay et al., Nature Biotechnology, "Clinical Development Success Rates for Investigational Drugs", 2014

>65% Faster time to Phase 3

Time from lead optimization to Ph3

	7			7.0y
	6					First 2 BridgeBio
	5
Years					programs
4
				2.8y
	3							2.0y
	2
	1
	0
		Industry	ATTR	Gorlin
			average	(Eidos)	(Pelle)

Sources: Paul et al., Nat Rev Drug Disc, "How to

improve R&D productivity: the pharmaceutical industry's grand challenge.", 2010

>8x	Better return on
investment

Total return on investment

[Enerprise value]/[APIC - cash on hand]*

35					First 2 BridgeBio
				programs
30
				23.2x
25
20										15.5x
15
10
5			2.3x
0
		NBI		ATTR		Gorlin
		median**	(Eidos)	(Pelle)***

*As of 1/10/2020 close

**Includes all NBI constituents with market value <$20bn

***Calculated as total consideration from LEO Pharma transaction divided by total burn to date

Sources: FactSet

Targeting genetic disease has higher average probability of success and BridgeBio has demonstrated higher ROI and shorter development time in its first 2 programs

7

A rapidly-advancing pipeline

Since our inception, we have actively built our pipeline through business development efforts, including the acquisition and in-licensing of assets, and advancing programs through internal stage-gates

Growth of assets in our pipeline:

20

							16
Total			9
programs	5
1
2015	2016	2017	2018	2019

Advancement of product candidates through key stage-gates:

		Lead-Opt	IND enabling	Ph1	Ph2	Ph3
	2016
Internal		+1
2017
		+1
program
advancement	2018
	+1		+1
	2019
		+6	+1		+3

8

Our pipeline of 20+ genetic medicines spans multiple therapeutic areas and drug modalities

Small molecule Topical small molecule Biologics Gene therapy

Portfolio

Patient

Pre-Clinical

Clinical

Program1

Drug mechanism

Diseases

pop.

Modality

segment

IND-

(US+EU)2

Discovery

Phase1

Phase 2

Phase 3

enabling

Mendelian

AG10

TTR stabilizer

ATTR-CM

>400K

BBP-870

cPMP replacement

MoCD type A

100

NDA

Infigratinib

Low-doseFGFR1-3i

Achondroplasia4

55K

BBP-711

GO1 inhibitor

PH1 / FSF

5K / 1.5M

BBP-761

Succinate prodrug

LHON

20K

BBP-671

PanK activator

PKAN / OA

7K

BBP-418

Glycosylation substrate

LGMD2i

7K

Encaleret

CaSR antagonist

ADH1 / HP

2K / 200K

New program

BBP-551

Synthetic retinoid

LCA / RP

3K

New program

BBP-472

PI3Kβi

PTEN autism

120K

New program

Genetic

BBP-0093

Topical SMOi

Gorlin / BCC

120K

Dermatology

BBP-589

Recombinant COL7

RDEB

1.5K

BBP-681

Topical PI3Kαi

VM / LM

117K

BBP-561

Topical KLK 5/7i

Netherton

11K

Targeted

Infigratinib

FGFR1-3i

FGFR+ tumors

37K

Oncology

BBP-398

SHP2i

Multiple tumors

>500K

BBP-454

Pan-mutant KRASi

KRAS+ tumors

>500K

BBP-954

GPX4i

Multiple tumors

>500K

Gene Therapy BBP-631

21-OH gene therapy

CAH

>75K

BBP-812

ASPA gene therapy

Canavan

1K

New program

BBP-815

TMC1 gene therapy

Genetic hearing loss

10K

1 Each of our programs is housed in a separate subsidiary; 2 Patient population: Prevalence except for asterisked figures which represent incidence; 3We are party to an option agreement pursuant to which LEO Pharma A/S has been granted an exclusive, irrevocable option to acquire PellePharm, including the BBP-009 program. If the option is exercised by LEO Pharma A/S, we will no longer have rights to develop and commercialize BBP-009. See "Business -Our Material Agreements-BBP-009 (Patidegib): Option Agreement with LEO Pharma A/S. 4Protocol submitted to Australian local ethics committed, IND submission to FDA expected 2020.

9

Low-dose FGFR inhibitor (infigratinib) for achondroplasia

Achondroplasia overview:

• Prevalence: 55,000 (US+EU) - one of the most common genetic conditions
• Genetic driver: FGFR3 activation
• Pathophysiology: Up regulation of STAT1 and MAPK in the growth plate cause cranial, spinal, and stature symptoms

Features of a best-in-class medicine for achondroplasia:

• Direct targeting of FGFR3 and normalization both STAT1 and MAPK signaling pathways
• Potential to address all drivers of symptoms, including cranial, spinal and stature issues
• Oral dosing, the most convenient solution for children with achondroplasia and their families

Claudia, child with achondroplasia

10

Best-in-class approach to treating achondroplasia directly at its genetic source

ACH FGFR3 gain-of-function mutation causes:

• 2-3xover activation of the receptor
• Up-regulationof downstream pathways STAT1 and MAPK
• Aberrant growth plate development causes cranial, spinal, and stature symptoms

Low-dose infigratinib is able to:

• Directly inhibit the causal gain-of-function mutation in FGFR3
• Normalize both the STAT1 and MAPK signaling pathways
• Demonstrate clear macro and microscopic improvements on foramen magnum, intervertebral discs, and long bones in validated preclinical model

							FGF
			FGFR3
			G380R
			mutation			Growth plate chondrocyte
		Low-dose					CNP analogues indirectly
		infigratinib
						block MAPK
On target, selective
inhibition of FGFR3 directly
blocking both STAT1 and
MAPK	STAT1			MAPK

Misregulated growth plate development

Source: Ornitz DM et al. Developmental Dynamic 2017; Richette Joint Bone Spine 2007; Unger Curr Osteoporos Rep 2017, Hoover-Fong Am J Gen Med 2017

11

Low-dose infigratinib improves all the key drivers of clinical symptomology in the validated ACH mouse model

1 Cranial bone issues

17%	6%
increase in	increase in AP
FM area	skull length

May lead to decrease in foramen

magnum stenosis and fewer surgeries

FGFR3 WT	FGFR3Y367C/+	FGFR3Y367C/+
No treatment	No treatment	Infigratinib tx

2 Disorders of the spine

12%	73%
increase in	increase in
L4-L6 length	disc width

May lead to decrease in spinal stenosis,

possibly reducing need for surgery

3 Disproportionate short stature

21%	33%
increase in	increase in
femur length	tibia length

May lead to increased stature

and proportionality

Source: Komla-Ebri et al. J Clin Inv 2016

Note: percent increase compared to vehicle treated FGFR3Y367C/+ mouse, infigratinib treatment with 2mg/kg subcutaneous dose

12

Low-dose infigratinib showed best in-class preclinical profile in the validated achondroplasia mouse model

Preclinical data from infigratinib and other investigational achondroplasia therapies

Percent increase compared to non-treated mouse

Company/		MOA		Route
Asset

Selective

Infigratinib FGFR1-3i Oral

Vosoritide	CNP analogue Daily SQ
(BMN111)

TransCon	CNP analogue Weekly SQ
CNP1

FGFR3 decoy Weekly SQ

Reifercept

(TA-46)

Status

Ph2 lead-in

ongoing2

Pivotal

Ph2 lead-in

ongoing

Ph1

Mouse model

FGFR3Y367C/+

FGFR3Y367C/+

FGFR3Y367C/+

FGFR3ACH/+

Tibia length		Femur length

33% 21%

7%5%

12%*

9%*7%*

Foramen

magnum area

16%

No

known

publically available data

L4-L6 height

12%

3%

Source: Komla-Ebri et al. J Clin In2v 2016, Lorget et al. Am J Hum Genet 2012, Garcia et al. Science Trans Med 2013, Breinholt ENDO 2017

Note: subcutaneous doses, percent increase compared to vehicle treated FGFR3Y367C/+, FGFR3ACH/+ mouse as noted in "Mouse model" columns Infigratinib treatment with 2mg/kg subcutaneous dose

1Based on vosoritide continuous infusion; *Value estimated using DigitizeIt. 2Protocol submitted to Australian local ethics committed, IND submission to FDA expected 2020.

13

The PROPEL clinical program is enrolling and will provide POC in 2021

Observational run-in

Ph2 Dose-finding (n=40)

Expansion (n=20)

Children are followed

for a minimum of 6 months to establish baseline annualized growth velocity (AGV)

Dose level 4

n=10

Dose level 3

n=10

Dose level 2

n=10

Dose level 1

n=10

Select dose

12 month long-term extension

20 new subjects for expansion

Key inclusion criteria

• Children 2.5 - 10 years old

• Clinical and molecular ACH diagnosis

Primary objectives	Primary objectives
• Baseline annualized growth velocity	• Identify safe therapeutic dose for
(AGV)		expansion / pivotal study
	•	Safety and tolerability
	•	Change from baseline in AGV

Primary objectives

• Long-termsafety and efficacy

14

Recombinant Collagen 7 for recessive dystrophic epidermolysis bullosa (RDEB)

RDEB overview:

• Prevalence: 1,500 (US + EU)
• Genetic driver: Collagen 7 (COL7) deficiency
• Pathophysiology: Systemic impairment of dermal- epithelial cohesion throughout various tissues leading to painful blistering on the skin, GI tract, and oral cavity

Features of a best-in-class medicine for RDEB:

• Treating RDEB at its genetic source, by replacing missing COL7 protein via a simple IV infusion
• Potential to address burden of RDEB beyond the skin, including systemic manifestations
• Proactively address wound formation and healing, rather than reactively treat lesions

Bardy, child with

RDEB

15

Recombinant collagen 7 for recessive dystrophic epidermolysis bullosa (RDEB)

RDEB COL7 loss-of-function mutations cause:

• Near complete loss of COL7 at epithelial junctions on the skin and throughout the body
• Painful erosions and blistering on the skin, GI tract, and oral cavity
• Failure to thrive, decreased life span, high risk for squamous cell carcinoma

Our systemic COL7 replacement is designed to:

• Replace COL7 at epithelial junctions throughout the body
• Address the systemic burden of RDEB including on the skin, GI tract and oral cavity
• Proactively address wound formation and healing globally rather than reactively treat lesions

16

Recombinant COL7 distributes systemically, leading to survival benefits in the RDEB mouse model

A single intravenous injection of recombinant COL7 distributed to epithelial barriers throughout the body (skin, oral cavity, GI tract), in a dose-dependentmanner

This led to a significant survival benefit in COL7-treatedanimals

Intravenous	Vehicle			25						23
COL7	(%intensity
Skin (abdomen)			15				13
		stainingCOL7		20
Tongue		positive)	10			6
				5		0
				0
COL7 is stained green in images above				Vehicle	5ug		16ug		28ug
e = epiderma

d = dermal

COL7

Source: Hou & Chen, Journal of Investigative Dermatology 2015

Probability of survival (%)

100								Vehicle
80
							COL7 (IV)
60
40
20

0

0 20 40 60 80 100 120 140 Days

17

Ongoing randomized, dose-escalation Phase 1/2 proof-of-concept clinical study in adults with RDEB

• First patient dosed in 1Q19
• Anticipate clinical POC in 1H20

Six doses

Patient

enrollment

Recombinant

COL7 (BBP-589)

8-week

(adults with

RDEB

diagnosis)

Randomization 1:1

Cross overfollow up

period

Saline

Day 0 wk2 wk4 wk6 wk8 wk10

Cohort 1: 0.1 mg/Kg	Cohort 2:0.3 mg/Kg	Cohort 3:1 mg/Kg
N=2	N=4	N=8
KEY INCLUSION CRITERIA		PRIMARY ENDPOINT
▪ Adult with RDEB diagnosis		▪ Safety and tolerability
▪ Deficiency but not total loss of COL7 protein

▪ At least 1 wound >20cm2 for ≥6 weeks

KEY SECONDARY ENDPOINTS

KEY EXCLUSION CRITERIA

• Known hypersensitivity to BBP-589
• Received investigational RDEB agent in last 6 months

• Pharmacokinetics
• COL7 deposition in skin biopsies
• Change in healing of up to 5 chronic wounds
• Patient reported outcomes (itch, QoL)

18

Targeted Oncology Portfolio

Andrea, CCA patient

World-class oncology team drives our discovery and development

• Eli Wallace: CSO Oncology
• Frank McCormick, Chairman of Oncology
• Richard Scheller, Chairman of R&D

We target driver mutations in genetically defined cancers…

• FGFR1-3i for FGFR+ cancer: Near-term revenue in CCA, multiple expansion indications
• Pan-mutantKRASi for KRAS+ cancer: Platform approach in partnership with NCI RAS initiative

…while also focusing on novel targets with extensive academic validation

• SHP2i for multiple tumors (10+ recent papers in Nature, Science, Nature Medicine)
• GPX4i for multiple tumors (10+ recent papers in Nature, Cell, Cancer Cell)

Program	MOA	Disease	Stage	Next update
Infigratinib	FGFR1-3 inhibitor	FGFR+ cancer	Ph3	Pivotal CCA data 2020, NDA 2020
BBP-398	SHP2 inhibitor	Multiple tumor types	Pre-IND	IND submission in 2020
BBP-454	Pan-mutant KRAS	KRAS+ cancer	Discovery	Clinical candidate nomination
inhibitor
BBP-954	GPX4 inhibitor	Multiple tumor types	Discovery	Clinical candidate nomination

19

KRAS: multiple shots on goal with our pan-mutant inhibitor programs - each with a unique MOA targeting a novel pocket

KRAS activation in cancer is a multistep process

Receptor tyrosine kinase signals (EGFR, FGFR, etc)

Our programs target different steps of the KRAS activation process

Program 1: C185 targeting	Program 2: H95 targeting
• Blocks KRAS from tethering	• Directly binds activated KRAS
• Blocks conversion of inactive	• Inhibits KRAS from signaling
KRAS GDP to active KRAS GTP	through effectors

	KRAS	KRAS
	GTP
	GDP
2	KRAS is
	activated by
KRAS	RTK signaling
GDP		3

KRAS GDP

KRAS GTP

Effector

1 KRAS must tether to the cell membrane to be activated

Active KRAS drives cancer proliferation and survival

KRAS tethering is blocked - cancer growth is inhibited

Activated KRAS signaling is inhibited

20

SHP2: Compounds from the BBP-398 series appear to restore sensitivity to osimertinib in resistant NSCLC models

MOA		Key data

Receptor tyrosine kinase signals (EGFR, ALK, etc)

pY
pY		KRAS
pY SHP2	SOS
GTP
BBP-398

• Growth factor signaling through mutant or wild- type receptors causes pathway activation
• SHP2 connects RTK signaling to downstream SOS/RAS activation
• Our compound potently traps SHP2 in an inactive state, thereby blocking downstream oncogenic signaling

Source: AACR-NCI-EORTC meeting 2019

21

GPX4: Potential first-in-class therapy for a novel cancer target

MOA

Altered cancer		Treatment
metabolism		resistant state

Key data

In vivo monotherapy activity in a renal cell carcinoma mouse model

Model: 786-O RCC xenograft (VHL LOF, p53 LOF)

Lipid peroxidation and

ROS accumulation

GPX4 GPX4i

Ferroptosis and cancer cell death

▪ GPX4 was recently identified as a key tumor

dependency in multiple CRISPR screens and

)

3

T u m o r V o lu m e (m m

6 0 0	B B IO G P X 4 i 4 m p k B ID s u b Q
	V e h ic le
4 0 0

2 0 0

0

0

2

4

6

D a y s o f tre a tm e n t

Rapid tumor regression after only 7 days of dosing

8

	mechanistic studies
▪	GPX4 allows tumor cells to survive by
	neutralizing toxic lipid peroxides
▪	Our approach is to directly inhibit GPX4, thereby
	triggering cancer death through ferroptosis

Synergy with targeted therapies and immunotherapy using in vitro models

22

Infigratinib (FGFRi): Near term revenue in CCA and multiple large expansion opportunities

Indication

FGFR2+ cholangiocarcinoma

FGFR3+ urothelial carcinoma

FGFR fusion- positive tumor agnostic

Key Data

39% ORR

in patients with ≤1 previous

line of treatment

25% ORR

in metastatic relapsed refractory setting suggests clear activity in this tumor

5 tumor types

Showed response to infigratinib in Ph1/2

Status	Next Update
▪ Enrollment complete in	▪	Updated pivotal data
2L Ph2 pivotal cohort		2H20
▪ Ph3 in 1L study enrolling	▪	NDA submission 2H20
		▪	2021 launch

▪ FPI for Ph3 in adjuvant	▪ Complete enrollment in
setting in 1H20	Ph3 adjuvant study

▪ FPI for Ph2 signal	▪ Potential Ph2 data 2021
optimization study in 1H20

SOURCE: Javle M et al. ESMO 2018, Pal S et al. Cancer Discovery 2018, data on file

23

Gene Therapy Portfolio

Experienced team with track record in gene therapy

Partnered with top academics in the gene therapy space

• Guangping Gao, Ph.D (UMass)
• Pierre Bougneres, M.D., Ph.D. (INSERM)
• Jeff Holt, Ph.D (Boston Children's)

Congenital adrenal hyperplasia (BBP-631)

• One of the largest known AAV gene therapy markets (prevalence 75K US+EU)
• Low threshold to correct phenotype, validated by human genetics
• Durable transgene delivery and expression for 6m in NHP study

Canavan disease (BBP-812)

• Lethal, degenerative, neuromuscular disease
• Precedented AAV9 serotype with safety shown in compassionate use case

TMC1-driven hearing loss (BBP-815)

• Delivers functional copy of TMC1 gene allowing transmission of auditory stimuli
• Nature Communications publication shows significant rescue of hearing function in diseased mice

Program	MOA	Disease	Stage	Next update

Vayle, child with Canavan

BBP-631	21-OHase gene therapy	Congenital adrenal
hyperplasia
BBP-812	ASPA gene therapy	Canavan disease
BBP-815	TMC1 gene therapy	Genetic hearing loss

Pre-IND	IND submission in 2020
Pre-IND	IND submission in 2020
Discovery	Clinical candidate nomination

24

21-OH gene therapy for CAH: NHP study showed durable transgene expression; 5-10% of WT enzyme may be sufficient for clinical impact

Genotype-phenotype studies show that >5-10% of enzyme activity results in nonclassical

CAH

• Due to the high enzymatic efficiency/selectivity of 21- OHase, only a small amount of enzyme is required to rescue the phenotype

Source: ESGCT 2019

Mouse studies show a VGC of

only 0.13 at 18 wks was sufficient for phenotypic reversal

VGC from the whole adrenal gland was

0.13 at wk 18

• At 15 weeks in treated mice, progesterone (the key substrate of 21OHase in mice) was significantly reduced vs untreated mice

NHP studies show sustained VGC and RNA out to at least 6 months

BBP-631 vector levels in the adrenal gland

• Mean vector genome copies per cell appear stable at 24 wks

BBP-631 mRNA expression in the adrenal gland

• Transgene expression is dose- dependent and stable out at 24 wks

25

ASPA gene therapy for Canavan: Phenotypic correction in a lethal mouse model and broad CNS transduction in NHPs

Mouse studies show a VGC of only 0.13 at 18 wks was sufficient for phenotypic reversal

Effect of BBP-812 on rotarod and

balance beam, ASPA KO mice (untreated

vs 3 different doses) and WT mice

• ASPA KO mice treated with at least 2.6e13 vg/kg had survival and performance on motor function tests fully rescued. Mice treated at 2.6e14 vg/kg outperformed WT mice.

Source: ESGCT 2019

NHP studies show broad CNS distribution with

IV delivery

Vector copies per diplome in various

CNS regions in NHPs

• IV delivery of BBP-812 showed superior transduction of several CNS regions compared to ICV and IT delivery

26

AG10 for TTR Amyloidosis (Eidos)

• Addressing large and growing need in ATTR, a fatal disease affecting >400K patients
• Targeting the disease at its source by stabilizing TTR, a genetic and clinically validated mechanism
• Advancing AG10, a potential best-in-classdrug that mimics naturally occurring rescue mutation
• Phase 2 open label extension study suggests potential to reduce mortality and cardiovascular hospitalizations at 15 months
• Executing Phase 3 study in ATTR-CMwith top- line data 2021

Art, ATTR-CM patient

27

AG10 structurally mimics disease-protective mutation by hyper-stabilizing TTR

	Disease-protective T119M mutation			AG10-bound TTR

Strong inter-monomerH-bonds observed via X-ray crystallography

Unique binding mode vs other stabilizers

28

Serum TTR levels, a prognostic indicator of survival, increased upon AG10 treatment and were maintained throughout Ph 2 study

Serum TTR concentration

mg/dL, mean ± SEM

AG10 WT1

35							+39%	AG10 Variant1
30			OLE baseline				+56%	Placebo WT
25								Placebo Variant
20
15								Lower limit of
10			OLE baseline					normal = 20 mg/dL2
5
0
1	14	28	1	14	45	90	180

N WT	35	35	34	35	35	33	33	32
N Variant	13	14	13	12	11	12	12	10
		AG10-201 (R)				Rollover			AG10-202 (OLE)

AG10-202 (OLE) Visit Day

1 400mg and 800mg BID AG10 groups pooled during randomized portion

2 Defined as the lower limit of the reference interval for the serum prealbumin (TTR) clinical laboratory assay

29

Deaths and CV hospitalizations reported in AG10 Phase 2 OLE were lower than in placebo-treatedATTR-ACT participants

All-cause mortality at 15 months

Participants died or receiving transplant (%)

-44%

15.3%

8.5%

Cardiovascular hospitalizations at 15 months Participants with ≥1 CV hospitalization (%)

-39%

41.8%

25.5%

Placebo	AG10	Placebo	AG10
ATTR-ACT Phase 3	Phase 2 OLE	ATTR-ACT Phase 3	Phase 2 OLE

Phase 3 ATTRibute study expected to complete enrollment in 2H20

1 Based on routine adverse event reporting

Note: These data are based on a cross-trial comparison and not a randomized clinical trial. As a result, the values shown may not be directly comparable

30

Fosdenopterin (cPMP replacement) for MoCD type A

Genetic driver: MOCS1 / cPMP depletion

Prevalence (US + EU): 100

• Addressing an extreme unmet medical need in molybdenum cofactor deficiency (MoCD) type A, a progressive and rapidly fatal CNS disorder (median survival <4 years)
• Targeting the disease at its source by directly replacing cPMP, the missing metabolite that causes CNS toxicity

Elliott, child with MoCD type A

• Potentially life saving therapy with compelling pivotal data showing prolonged survival, seizure control and ambulation vs natural history
• Rolling NDA submission initiated in 4Q19, under FDA Breakthrough Therapy Designation

31

We presented data from our natural history study in MoCD type A at SSIEM 2019

• Median survival time of <4y highlights urgent need for a new medicine
• Data will play an important role in our NDA data package

32

Our current pipeline has the potential to treat nearly 3 million patients in the US and EU alone

Patient population by development	Breakdown of clinical-stage
stage	assets

'000s)	3,000				2,690
2,500
+ EU,
2,000			1,168
(US
1,500
population
1,000		705
Patient	500	817
0
	Clinical	IND-	Discovery	Total
			enabling

Indication	Population
ATTR	400,000
Hypoparathyroidism	200,000
Basal cell carcinoma	120,000
Achondroplasia	55,000
FGFR+ cancer	37,000
Inherited retinal dystrophy	3,000
RDEB	1,500
MoCD type A	100
Total:	817,000

Our product platform has the potential to deliver diversified and sustainable

revenue growth beginning in 2021

33

Assessing BridgeBio

Criteria

High probability of success

1

Relevance

• Historically higher probability of success for genetic disease drugs
• BridgeBio's early programs have outperformed historical probabilities

Today's Talk

Current

Pipeline

Progress

	Number of programs	• We find great science and unlock its potential for
2	patients
	• Always searching for the next PellePharm or Eidos
		• Scale allows for objective assessment and failure

New

Programs

	Capital efficiency	•	Generate value by making each program ROI-positive	Spend to
	IND
3	•	Driven by judicious use of capital at the high-risk

preclinical stages

34

We are announcing four new programs today including two entering Phase 2 trials

Mechanism: Ca sensing receptor antagonist	Mechanism: Synthetic retinoid
Diseases and prevalence:		Diseases and prevalence:
Autosomal dominant	Hypoparathyroidism				Leber's congenital amaurosis
			/ retinitis pigmentosa (RPE65
hypocalcemia type 1	200,000
			and LRAT)
2,000		US + EU
	2,000
US + EU
				US + EU
Modality: Small molecule		Modality: Small molecule
			Phase 2 ready				Phase 2 ready

Mechanism: PI3Kβ inhibitor	Mechanism: TMC1 gene therapy
Diseases and prevalence:	Diseases and prevalence:
PTEN autism	Genetic hearing loss
120,000	10,000
US + EU	US + EU
Modality: Small molecule	Modality: Gene therapy
Discovery	Discovery

We plan to announce multiple additional new programs in 2020

35

Encaleret (CaSR antagonist) for hypoparathyroidism

Encaleret targets disease at its source by selectively antagonizing the CaSR, a key regulator of calcium homeostasis

• Opportunity to develop encaleret was identified in collaboration with global experts at the NIH
• Being prosecuted by the BridgeBio cardiorenal group

Encaleret is a potential 1st in class CaSR antagonist with differentiated profile for hypoparathyroidism

• Initial genetically-defined population of autosomal dominant hypocalcemia type 1 (ADH1), provides high probability of success
• Potential for expansion into broader hypoparathyroidism indication (~200K patients in US & EU)

Prior clinical experience with encaleret enables accelerated clinical development

• Well tolerated in >1,300 human subjects and increased serum calcium in a dose-dependent manner
• IND application submitted in late 2019 with Phase 2b study in ADH1 planned to initiate in 1H20
• Proof-of-conceptdata in ADH1 expected in 2021

36

Assessing BridgeBio

Criteria

High probability of success

1

Relevance

• Historically higher probability of success for genetic disease drugs
• BridgeBio's early programs have outperformed historical probabilities

Today's Talk

Current

Pipeline

Progress

	Number of programs	• We find great science and unlock its potential for
2	patients
	• Always searching for the next PellePharm or Eidos
		• Scale allows for objective assessment and failure

New

Programs

		Capital efficiency	•	Generate value by making each program ROI-positive	Spend to
		IND
	3	•	Driven by judicious use of capital at the high-risk
				preclinical stages

37

We have brought assets forward more efficiently than industry average

Operationally Efficient Platform

• Our track record to date is ~$6mm to IND and is ~$23mm IND to POC
• We aim to rapidly and decisively advance our product candidates to objective critical decision points
• We field a minimum viable team for each asset, with the goal of ensuring that each program has sufficient personnel to fit its purpose while reducing excess overhead cost

Spend to IND ($mm)

15.0
					-63%
	8.2
		6.0			5.5
			4.2	3.6
Industry	ATTR	Gorlin	RDEB	ADH1	BBIO
Average	(Eidos)	/BCC	(PTR)	(Calcilytix)	Average
		(Pelle)

Note: BBIO values exclude license and acquisition costs.

Spend IND to POC ($mm)

55.0
	36.6		-58%
			22.9
		9.3
Industry	ATTR	Gorlin	BBIO
Average	(Eidos)	/BCC	Average
		(Pelle)

38

2019 included a range of accomplishments across our development programs and operations

Clinical, regulatory, and scientific

• ATTR: initiated Ph3 trial, presented Ph2 open-label extension data
• Achondroplasia: initiated Ph2 lead-in, established therapeutic window between human safety database and projected efficacious achondroplasia doses
• RDEB: initiated Ph2 POC trial
• MOCD Type A: initiated rolling NDA
• BCC: completed Gorlin Ph3 enrollment; initiated Ph2 high frequency BCC
• Oncology: SHP2 combination data w/ MEK, EGFR, KRAS augmenting inhibition; GPX4 demonstrated monotherapy activity in mouse model
• CCA: fast track designation, completed second line efficacy cohort
• CAH: demonstrated 6-month durability in adrenal cortex
• Canavan: demonstrated broad CNS distribution using IV route of administration

Operations and finance

• Building commercial organization: Jennifer Cook, BOD member and commercial advisor; appointed Matt Outten as CCO
• Financing: raised over $650M in IPO and crossover

BridgeBio: Commercial build out

Top talent makes a		Building awareness		Gearing up for genetic
difference										disease launches
										•	Critical patient identification
• CCO: Matt Outten											capabilities expanded in rare
										diseases with multiple data
• 20+ years pharma/biotech											sources
• Multiple commercial leadership										•	Allows better target planning,
positions across sales, marketing,											asset review, and appropriate
market access											resource allocation
• Led the successful launch of										•	Developing best in class HUB
Imbruvica for 6 indications											and patient assistance
• 25 BBIO leadership roles:											programs in prep for commercial
										launches
• VPs of Marketing, Market Access,										•	Developing tailored launch
Distribution, Commercial Operations,
										plans for each sub, from brand
Directors of Marketing and Training,
										development to promotional
Data Analytics and Operations
										material and in-field team training
• In-field teams established: Clinical
Trial Liaisons, Professional Services

We are building a leading integrated pharma company

Fully

integrated PharmCo

Mendelian	Somatic
rare disease	cancers

Commercial capabilities

Late-stageEarly-stage

clinical drug discovery

Oligo-

Small

Therapeutic

Gene therapy

nucleotide

molecule

proteins

Asset finding

Experienced

Optimal

Preferred

Academic

R&D

corporate

partnerships

& selection

partnerships

leadership

structure

w/CRO & mfg.

41

Multiple catalysts in 2020-2021

2020

ESTIMATED

2021

1H

• Recombinant COL7 for RDEB: Topline Ph1/2 data
• FGFRi for cancer: FPI Ph3 adjuvant urothelial carcinoma study
• FGFRi for cancer: FPI Ph2 FGFR fusion tumor agnostic Ph2 study
• New program announcements

2H

• FGFRi for cancer: Pivotal 2L CCA data
• Low-doseFGFRi for achondroplasia: Begin dosing Ph2
• TTR stabilizer for ATTR: Complete enrollment of ATTR- CM Ph3
• FGFRi for cancer: Submit NDA for 2L CCA
• cPMP for MoCD type A: Complete rolling NDA submission
• CAH gene therapy: Complete IND submission

FY

• TTR stabilizer for ATTR: Topline data Ph3 Part A in
  ATTR-CM
• Topical SMOi for Gorlin: Topline Ph3 data
• Low-doseFGFRi for achondroplasia: Ph2 PoC data
• CAH gene therapy: Ph1/2 PoC data
• FGFRi for cancer: 2L CCA approval and launch
• cPMP for MoCD type A: Approval and launch

$612mn cash balance as of 9/30/19 provides runway through 2021

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