PharmGPS Validations

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Validations

2014 • Masitinib + Riluzole (Amyotrophic Lateral

• Gantenerumab (Alzheimer’s Disease) Sclerosis (ALS))
• Otezla (Ankylosing Spondylitis)
• Plegridy (Multiple Sclerosis) • omecamtiv mecarbil Oral (CHF)
• Radicava (Amyotrophic Lateral Sclerosis (ALS))
2015 • Siponimod (MS)
• Sirukumab (Rheumatoid Arthritis)
• Brilinta + acetylsalicylic acid (ACS) • Spinraza (SMA)
• Filgotinib (Rheumatoid Arthritis) • Stelara (Crohn’s Disease)
• Ocaliva (NASH) • Taltz (Psoriasis)
• Ozanezumab (Amyotrophic Lateral Sclerosis (ALS)) • Tecentriq (NSCLC)
• Repatha (Dyslipidemia) • Upadacitinib (Rheumatoid Arthritis)
• Savaysa (Atrial Fibrillation) • Xeljanz Modi ed release (Rheumatoid Arthritis)
• Tenapanor (IBS) • XP23829 (Psoriasis)
• Zinbryta (Multiple sclerosis)
2016
2017
• Alo sel (Cx601) (Crohn’s Disease)
• Arzerra (Multiple sclerosis) • ALKS 8700 (Multiple sclerosis)
• Bevespi Aerosphere (COPD) • ArmonAir RespiClick (Asthma)
• Brigatinib (Non-Squamous NSCLC) • Baricitinib (Rheumatoid Arthritis)
• Cimzia (Psoriasis) • Dupixent (dupilumab) (Atopic Dermatitis)
• Cinqair (Asthma) • Keytruda + Alimta + Carboplatin (NSCLC)
• Dipraglurant (PD) • Lupuzor (SLE)
• Eltoprazine (PD) • Ocrevus (MS)
• Eucrisa (PD) • Ozanimod (MS)
• Filgotinib (Crohn’s disease) • Sacituzumab govitecan (TNBC)
• glycopyrrolate nebulized (COPD) • Tildrakizumab (Psoriasis)
• GS-5745 (Crohn’s Disease) • Trulance (IBS-C)
• Guselkumab (Psoriasis) • Zykadia (NSCLC)
• idalopirdine (Alzheimer’s Disease)
• Lebrikizumab (Asthma)

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Gantenerumab (Alzheimer’s Disease)

Gantenerumab: Primary Endpoint Not Met
(Segment : Mild to Moderate Alzheimer’s Disease, Phase: Discontinued, Company: Roche)
December 19th 2014: Roche provides update on gantenerumab development programme

Performance Benchmark

Exelon Patch

Exelon Patch 3 3
3.61, 2.9 EFFICACY
SAFETY
crenezumab SOC
3.1375, 2.25

elenbecestat

Gantenerumab Gantenerumab Gantenerumab

3.1375, 2.25 3.03, 1.85

2.5125, 1.85

SOC Phase III analysis Discontinued analysis 11 11
EFFICACY SAFETY
Phase III analysis Discontinued analysis

In December 2014, Roche announced the decision to discontinue gantenerumab in prodromal (pre-dementia)
Alzheimer’s disease, based on results of a pre-planned futility analysis and recommendation by the independent
Data Monitoring Committee. Overall, patients treated with gantenerumab did not experience cognitive benefit
compared to patients treated with placebo, but there was evidence of efficacy in patients with faster progress-
ing disease who had higher exposure to the drug.

PharmGPS Prediction: Gantenerumab was rated as a weak molecule even by PharmGPS though
it had reached phase III. The announcement of recent results of gantenerumab not meeting its
primary endpoints validate PharmGPS analysis.

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Otezla (Ankylosing Spondylitis)

Otezla: Primary Endpoint Not Met
(Segment : DMARDs & Other therapies, Phase: Phase III, Company: Celgene Corporation)
July 9th 2014: Celgene Reports Results from the Phase III POSTURE Study Evaluating Oral OTEZLA® in

Ankylosing Spondylitis

Performance Benchmark

Rayos

4.25, 3.1 3 3
Rayos EFFICACY
SAFETY
SOC

1.92, 1.8 Otezla
VTP-43742
Otezla
Otezla 2.97, 1.65
2.32, 1.65

SOC Phase II analysis Phase III analysis 11 11
EFFICACY SAFETY
Phase II analysis Phase III analysis

In July 2014, Celgene Corporation announced results of its phase III POSTURE study evaluating OTEZLA, the
company's oral, selective inhibitor of phosphodiesterase 4 (PDE4), in patients with active ankylosing spondyli-
tis. Phase III POSTURE Study Did Not Achieve Primary Endpoint of ASAS20 at Week 16. The OTEZLA arms did
not achieve statistically significant improvement versus the placebo arm for the primary endpoint, the percent-
age of patients who achieve an ASAS20 response at week 16.

PharmGPS Prediction: PharmGPS did not rate Otezla as a molecule with good potential based on
phase II data and now with announcement of Phase III results of Otezla not meeting its primary
endpoint, PharmGPS assessment has been validated.

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Plegridy(Multiple Sclerosis)

Plegridy: Approved by FDA
(Segment :First line Rx for Relapsing MS, Phase: Marketed, Company: Biogen)
August 15th 2014: FDA Approves Plegridy (Pegylated Interferon Beta) For Relapsing MS

Performance Benchmark

4.2, 2.7 glatiramer acetate
4.11, 2.75 glatiramer
3.76, 2.75 3 3
Plegridy Plegridy acetate EFFICACY
SAFETY
Naturaferon Avonex SOC
3.75, 1.75 4.175, 2.5

Plegridy

SOC Phase III analysis Approved analysis 33 33
EFFICACY SAFETY
Phase III analysis Approved analysis

In August 2014, Biogen Idec announced that the FDA has approved PLEGRIDY (peginterferon beta-1a), a new
treatment for people with relapsing forms of multiple sclerosis (RMS). The FDA approval of PLEGRIDY is based
on results from one of the largest pivotal studies of beta interferon conducted, ADVANCE, which involved more
than 1,500 MS patients. PLEGRIDY reduced the risk of 12-week confirmed disability progression, as measured by
the Expanded Disability Status Scale, by 38 percent (p=0.0383) compared to placebo. PLEGRIDY also significant-
ly reduced the number of new gadolinium-enhancing [Gd+] lesions by 86 percent (p<0.0001) and reduced new or
newly enlarging T2-hyperintense lesions by 67 percent (p<0.0001) compared to placebo.

PharmGPS Prediction: Plegridy was rated as one of the front-runners in MS based on PharmGPS
analysis. With FDA approving Plegridy for MS, it has offered a safe and efficacious treatment
option for patients with MS.

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Ocaliva (NASH)

OCALIVA: PROMISING TREATMENT FOR NASH
Segment: Nonalcoholic Steatohepatitis, Phase: Phase III, Company: Intercept Pharmaceuticals)
May 19th 2015; Intercept Pharmaceuticals Announces Pivotal Phase 3 Clinical Trial of Obeticholic Acid in

NASH

Performance Benchmark elafibranor

2.4875, 2.75 elafibranor 3 2
ocaliva 2.625, 2.75 EFFICACY
SAFETY
Aramchol 2.825, 2.15 SOC
2.325, 2.45
ocaliva

oltipraz
2.275, 2.45

Ocaliva

elafibranor Ocaliva Ocaliva 23 22
Phase II analysis Phase III analysis EFFICACY SAFETY
Phase II analysis Phase III analysis

In May 2015, Intercept Pharmaceuticals announced that the company has initiated Phase III REGENERATE on the
basis of culmination of analysis of the Phase II FLINT trial that was conducted in patients with NASH. The trial
endpoint in Phase II trial was (Improvement in NAFLD Activity Score (NAS) by =2 points with no worsening of
fibrosis) which was met with high statistical significance. The predetermined significance threshold for ending
the trial was P less than .0031, but early results exceeded expectations with a significance of P = .0024. OCA also
demonstrated beneficial effect on liver damage. After 72 weeks of treatment (n=160; OCA=84; placebo=76), a
significant percentage of OCA-treated patients experienced complete resolution of their fibrosis (15% OCA vs. 4%
placebo, p=0.006)

PharmGPS Prediction: In January 2015, OCA was given breakthrough designation and with the
results announced for OCA in May 2015, it is most likely going to be the first drug to be approved
for NASH. PharmGPS predicted Ocaliva as one the top drugs for NASH based on phase II data and
the above events only validate this analysis. With no available therapies for NASH, Ocaliva brings
hope to patients suffering from this disease.

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Ozanezumab (Amyotrophic Lateral Sclerosis (ALS))

Ozanezumab: Discontinued for showing no benefit
(Segment :Mild to Moderate ALS, Phase: Discontinued, Company: GlaxoSmithKline plc)
August 1st 2015: Ozanezumab Fails to Show Benefit as ALS Treatment in Phase 2 Clinical Trial

Performance Benchmark

Riluzole

Nurown Riluzole 3 3
3.75, 2.75 EFFICACY
SAFETY
2.87, 2.1 SOC

2.27, 2
ibudilast

0.5, 1.3 2.22, 1.35 Ozanezumab
Ozanezumab
Ozanezumab
2.2, 1.3

SOC Phase II analysis Discontinued analysis 00 22
EFFICACY SAFETY
Phase II analysis Discontinued analysis

In February 2017, ozanezumab as a treatment of amyotrophic lateral sclerosis, failed to show any benefits. The
Phase II study’s main outcome was a combination analysis of the ALS Functional Rating Scale-Revised (ALS-
FRS-R) and overall survival, but at 48 weeks, no differences were reported between treatment and placebo 
groups in the scores. In other measures of efficacy, researchers noted that the group receiving ozanezumab had
numerically worse outcomes than those in the placebo group on all analysed outcomes. But these differences
were not statistically significant.

PharmGPS Prediction: Ozanezumab was rated as a low potential molecule in PharmGPS based on
early phase II results. Its discontinuation after phase II validates PharmGPS analysis.

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Repatha (Dyslipidemia)

Repatha: New Cholesterol lowering drug
(Segment :Hypertriglyceridemia, Phase: Marketed, Company: Amgen)
August 27th 2015: FDA Approves Amgen's New Cholesterol-Lowering Medication Repatha (evolocumab)

Performance Benchmark

Fenofibrate

4.375, 3.2 Fenofibrate 3 3
4.37, 3.2 EFFICACY
SAFETY
Trilipix SOC

3.75, 2.6 Repatha Lovaza
Olbetam 3.97, 2.45 4.375, 2.8

3.69, 2.45 Repatha
Repatha

SOC Phase III analysis Approved vanalysis 22 22
EFFICACY SAFETY
Phase III analysis Approved analysis

In August 2015, Amgen announced that the FDA has approved a new cholesterol-lowering medication, Repatha
™ (evolocumab) Injection. In Phase 3 trials, adding Repatha to background lipid-lowering therapy that included
statins resulted in intensive reductions in LDL-C levels with favorable effects on other lipid parameters. In
patients with clinical ASCVD or HeFH, Repatha reduced LDL-C by approximately 54 to 77 percent compared with
placebo.8 In a pivotal Phase 3 trial, 90 percent of clinical ASCVD patients who received Repatha in addition to
maximum doses of statins achieved a LDL-C level less than 70 mg/dL.5 In patients with HoFH, Repatha reduced
LDL-C by approximately 30 percent compared with placebo.

PharmGPS Prediction: Repatha in its earlier phases was identified as a potential candidate for
dyslipidemia by PharmGPS. Its approval in 2015 validated PharmGPS analysis.

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Savaysa (Atrial Fibrillation)

Savaysa: Approved for patients with AF
(Segment : Prevention of thromboembolism, Phase: Marketed, Company: Daiichi Sankyo Company Limited)

August 1st 2015: U.S. FDA Approves Daiichi Sankyo’s Once-Daily SAVAYSA™ (edoxaban) Tablets for
Reduction of Stroke Risk in Non-Valvular Atrial Fibrillation and for the Treatment of Venous Thromboembolism

Performance Benchmark

Pradaxa

Xarelto 3 3
3.35, 2.8 EFFICACY
SAFETY
Pradaxa 3.35, 2.75 SOC

Eliquis Savaysa 3.85, 2.65
3.35, 2.65 Savaysa
Savaysa

Plavix 33 33
3.25, 2.5 EFFICACY SAFETY
Phase III analysis Approved analysis
SOC Phase III analysis Approved analysis

In August 2015, Daiichi Sankyo Company Limited announced that the FDA has approved SAVAYSA (edoxaban)
tablets, an oral, once-daily selective factor Xa-inhibitor, to reduce the risk of stroke and systemic embolism (SE)
in patients with non-valvular atrial fibrillation (NVAF). The approved indications in the U.S. for SAVAYSA are
based on data from the ENGAGE AF-TIMI 48. In ENGAGE AF-TIMI 48, SAVAYSA was non-inferior to warfarin in
the overall study population for the primary efficacy endpoint of stroke or SE. SAVAYSA had significantly less
major bleeding in patients with NVAF, both in the overall study population  (HR, 0.80; 95% CI, 0.70 to 0.91,
p<0.001) and in patients with CrCL less than or equal to 95 mL/min (HR, 0.84; 95% CI, 0.73 to 0.97). In addition,
in the approved population, there were lower rates of intracranial hemorrhage with SAVAYSA compared to warfa-
rin in patients with NVAF (0.5% vs. 1.0% per year, respectively; HR, 0.44, 95% CI, 0.32 to 0.61).

PharmGPS Prediction: In its Phase III analysis, PharmGPS assessed Savaysa as one of the most
promising drugs for patients with Atrial Fibrillation. The announcement of FDA approval supports
this assessment and this approval brings in new hope for patients with Atrial fibrillation

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Bevespi Aerosphere (COPD)

Bevespi Aerosphere : Approved in US
(Segment: Moderate COPD ; Phase: Approved; Company: Astra Zeneca)
April 24th 2016 : Bevespi Aerosphere™ approved by the US FDA for patients with COPD

Performance Benchmark

Anoro Ellipta

3.975, 2.9 Anoro Ellipta 4.56, 2.95 3 3
EFFICACY
Daliresp Bevespi Aerosphere SAFETY
SOC
4.5625, 2.85

4.21, 2.2 4.56, 2.2

Bevespi Aerosphere Bevespi Aerosphere

Bevespi Aerosphere

SOC Phase III analysis Approved analysis 22 22
EFFICACY SAFETY
Phase III analysis Approved analysis

In April 2016, Astra Zeneca announced that the FDA has approved Bevespi Aerosphere (glycopyrrolate and
formoterol fumarate) inhalation aerosol indicated for the long-term, maintenance treatment of airflow obstruc-
tion in patients with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and/or emphy-
sema. The FDA approval is based on the PINNACLE trial programme, which demonstrated that Bevespi Aero-
sphere achieved statistically significant improvement in morning pre-dose forced expiratory volume in 1 second
(FEV1) at 24 weeks (p<0.001) versus its mono-components and placebo. Bevespi Aerosphere demonstrated a
significant improvement versus placebo on secondary endpoints of peak FEV1 within 2 hours post-dose, and
rescue medication usage.

PharmGPS Prediction: Bevespi Aerosphere was rated as one of the top molecules for COPD in
phase III. The FDA approval in April 2016 validates PharmGPS analysis making it the first product
approved using AstraZeneca’s Co-Suspension Technology

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Brigatinib (Non-Squamous NSCLC)

Brigatinib: NEXTGEN Promising ALK inhibitor
(Segment:2nd Line therapy for ALK rearrangement-positive NS-NSCLC, Phase: Filed, Company: Takeda
Pharmaceuticals) August 30th 2016; ARIAD Completes Rolling Submission of New Drug Application for

Brigatinib to the U.S. Food and Drug Administration

Performance Benchmark Zykadia

ensartinib Brigatinib 3
2.275, 3.8 3.55, 3.8 EFFICACY

2

SAFETY
SOC

Brigatinib ensartinib Brigatinib
2.475, 3.4 3.525, 3.4 Alecensa
Kadcycla
2.2, 1.5 4.05, 2.9

44 33

Zykadia Brigatinib Brigatinib EFFICACY SAFETY
Phase II analysis Filed analysis Phase II analysis Filed analysis

In August 2016 Ariad Pharmaceuticals which now have been acquired by Takeda Pharmaceuticals announced it
has completed the rolling submission of the New Drug Application (NDA) for its investigational anaplastic
lymphoma kinase (ALK) inhibitor, brigatinib, to the U.S. Food and Drug Administration (FDA). ARIAD is seeking
U.S. marketing approval of brigatinib for patients with metastatic ALK-positive (ALK+) non-small cell lung cancer
(NSCLC) who are resistant or intolerant to crizotinib. ARIAD’s NDA submission includes clinical data from its
Phase 1/2 and pivotal Phase 2 ALTA trials of brigatinib. With a median follow-up of 8.3 months, the data show
that, for patients treated with the 180 mg regimen with a seven day lead-in at 90 mg(Arm B), 54 percent achieved
an investigator-assessed confirmed objective response, the trial’s primary endpoint. In this arm, the median
progression free survival (PFS) exceeded one year (12.9 months). Additionally, a 67% confirmed intracranial
objective response rate was achieved in patients with measurable brain metastases.

PharmGPS Prediction: Brigatinib has been a front-runner in PharmGPS analysis even when it was in
early phase II (as shown above) and now the submission of rolling NDA validates PharmGPS’ early
analysis and it has the potential to be the next promising drug for NSCLC

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Cimzia (Psoriasis)

Cimzia: Promising Results Reported for Psoriasis
(Segment: Severe Psoriasis; Phase: Phase III; Company: UCB SA)
November 2nd 2016: CIMZIA® (certolizumab pegol) Phase 3 Trial Meets Co-primary Efficacy
Endpoints in Patients with Moderate-to-Severe Chronic Plaque Psoriasis

Performance Benchmark

Humira

Tildrakizumab Cimzia 3 2
EFFICACY
3.4, 2.65 4.42, 2.9 SAFETY
SOC
piclidenoson Cimzia 4.67, 2.45

2.825, 2.2 4.42, 2.55 Humira

Cimzia

SOC 2015 analysis 2016 analysis 34 22
EFFICACY SAFETY
2015 analysis 2016 analysis

In November 2016, UCB and Dermira, Inc. announced top-line results from CIMPASI-2 clinical trial evaluating the
efficacy and safety of CIMZIA® (certolizumab pegol) in adult patients with moderate-to-severe chronic plaque
psoriasis. In the CIMPASI-2 trial, CIMZIA demonstrated statistically significant improvements for both co-prima-
ry endpoints compared to placebo at both treatment doses. The CIMPASI-2 trial results are from the first of three
Phase 3 clinical trials to be reported evaluating CIMZIA in this patient population. The response rate for patients
achieving at least a two-point improvement to a final score of clear or almost clear skin on the PGA scale at week
16 was 71.6% for the 400 mg dose-treated patients and 66.8% for the 200 mg dose-treated patients, compared
to 2.0% for the patients receiving placebo.

PharmGPS Prediction: Cimzia was rated as one of the front-runners by PharmGPS in its early Phase
III analysis in the year 2015. With recent results announcement in 2016 of late stage phase III
results, Phase III prediction has been validated as Cimzia demonstrated significant results and met
its primary and secondary endpoints.

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Filgotinib (Crohn’s disease)

Filgotinib: Promising Treatment FOR Crohn’s Disease (CD) Progresses to Next Phase
(Segment: Moderate to Severe Crohn’s disease, Phase: Phase III, Company: Galapagos NV)

November 22nd 2016; Phase 3 study with filgo&nib ini&ated in Crohn's disease

Performance Benchmark Humira

FilgotiBnib FilgotiBnib 3 2
2.45, 2.7 3.1, 2.7 EFFICACY
SAFETY
mongersen SOC
2.9625, 2.7

risankizumab clarithromycin Filgotinib
2.325, 1.55 2.825, 1.7

ozanimod 33 22
2.275, 1.2 EFFICACY SAFETY
Phase II analysis Phase III analysis
Humira FilgotiBnib FilgotiBnib
Phase II analysis Phase III analysis

In November 2016 Galapagos NV reported the first dosing of a patient in the DIVERSITY Phase 3 study
with filgotinib in Crohn's disease (CD).This step may be considered as a good step as filgotinib repoted
significant results in phase Iib FITZROY study.The FITZROY study achieved the primary endpoint of clinical
remission at 10 weeks: the percentage of patients achieving a Crohn'sDisease Activity Index (CDAI) score
below 150 was significantly higher in patients treated with filgotinib versus patients receiving placebo.
Improvement in quality of life, histopathology, endoscopy assessment and biomarkers of inflammatory
activity were also observed at Week 10. Clinical responses were maintained from week 10 to week 20

PharmGPS Prediction: Filgotinib was rated as a molecule with good potential for Crohn’s disease
based on early phase II data. Its progression to next phase supports the fact about its potential and
as the next promising drug for treatment of CD

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glycopyrrolate nebulized (COPD)

glycopyrrolate nebulized : Accepted for review by FDA
(Segment: Severe COPD; Phase: Filed; Company: Sunovion Pharmaceuticals) October 13th 2016 :
Sunovion Announces FDA Filing Acceptance of New Drug Application for SUN- 101/eFlow® for the

Treatment of Patients with Chronic Obstructive Pulmonary Disease (COPD)

Performance Benchmark

Advair Diskus

Advair Diskus 3 3
EFFICACY
4.36, 3.1 SAFETY
SOC
4.1875, 2.95 Duaklir Genuair

glycopyrrolate nebulized 4.43, 2.6

3.55, 2.6 glycopyrrolate nebulized

glycopyrronium + formoterol + glycopyrrolate nebulized
budesonide

3.55, 1.35

SOC Phase II analysis Filed analysis 22 22
EFFICACY SAFETY
Phase III analysis Approved analysis

In October 2016, Sunovion Pharmaceuticals announced that FDA has accepted for review NDA for glycopyrrolate
nebulized.The NDA for SUN- 101/eFlow® is based on data from clinical trials in the GOLDEN (Glycopyrrolate for
Obstructive Lung Disease via Electronic Nebulizer) program, which included GOLDEN-3 and GOLDEN-4, two
Phase 3, 12-week, randomized, double-blind, placebo-controlled, parallel-group, multicenter, efficacy and safety
trials comparing SUN-101/eFlow® with placebo in adults with moderate-to-very severe COPD. These two studies
met their primary endpoints, showing that patients treated with SUN-101/eFlow® demonstrated a statistically
significant change from baseline in trough forced expiratory volume in one second (FEV1) at Week 12 versus
placebo.

PharmGPS Prediction: PharmGPS predicted glycopyrrolate nebulized as one of the top molecules
for COPD. FDA acceptance of its NDA validates the PharmGPS prediction.

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GS-5745 (Crohn’s Disease)

GS-5745 : Phase II study Terminates
(Segment: Moderate to Severe Crohn`s Disease ; Phase: Discontinued; Company: Pfizer Inc)

November 2nd 2016: Licensed product candidate update

Performance Benchmark

Humira

2.32, 1.55 4.5, 2.55 3 2
EFFICACY
risankizumab Humira SAFETY
SOC
GS-5745
GS-5745 GS-5745
2.2, 1.15
0.5, 1.15
olamkicept
2.15, 0.85

SOC Phase II analysis Discontinued EFFICACY 11
analysis Phase II analysis SAFETY
Discontinued analysis

In November 2016, Abzena announced that Gilead Sciences will not progress further GS-5745 for Cohn's
Disease. The reason for discontinuation was not disclosed. GS-5745 is a part of a range of products created
using Abzena’s Composite Human Antibody™ technology that its partners have been progressing into clinical
development.

PharmGPS Prediction: PharmGPS predicted GS-5745 as a molecule with a low potential for the
treatment of Crohn’s Disease in its Phase II analysis. With recent announcement of company
discontinuing this molecule, PharmGPS analysis has been validated.

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Guselkumab (Psoriasis )

GUSELKUMAB: SUPERIOR TO HUMIRA FOR PSORIASIS
(Segment: Severe Psoriasis , Phase: Filed, Company: Janssen Pharmaceu&cals)
October 1st 2016; New Phase 3 Data Show Significant Efficacy Versus Placebo And Superiority Of Gusel -

kumab Versus Humira

Performance Benchmark Humira

3.75, 3.4siliq

risankizumab guselkumab 3 2
3.45, 3.4 3.8, 3.3 EFFICACY
SAFETY
guselkumab humira SOC
3.35, 2.8 4.675, 2.6

2.85, 2.2 tildrakizumab Guselkumab
3.4, 2.8
picledeson

34 22

Humira guselkumab guselkumab EFFICACY SAFETY
Phase III Filed analysis Phase III analysis Filed analysis
analysis

In June 2016 Janssen Research & Development, LLC (Janssen) announced findings from the first of three pivotal
Phase 3 studies evaluating guselkumab, a subcutaneously administered anti-interleukin (IL)-23 monoclonal
antibody in late-stage development for the treatment of adults with moderate to severe plaque psoriasis. Data
from the VOYAGE 1 trial showed significantly higher proportions of patients receiving guselkumab achieved
cleared/minimal disease compared with patients receiving placebo, as defined by at least a 90 percent
improvement in the Psoriasis Area Severity Index (PASI 90, near complete skin clearance) and an Investigator’s
Global Assessment (IGA) score of cleared (0) or minimal disease (1) at week 16, the study co-primary endpoints.
The VOYAGE 1 trial also included an active comparator arm evaluating guselkumab versus Humira®
(adalimumab), and showed the superiority of guselkumab across major study endpoints and through 48 weeks of
treatment.In the VOYAGE 1 study, the co-primary endpoints were met at week 16, with 85.1 percent of patients
receiving guselkumab 100 mg at weeks 0 and 4 and then every eight weeks achieving cleared (IGA 0) or minimal
disease (IGA 1) compared with 6.9 percent of patients receiving placebo (P < 0.001). Nearly three-quarters of
patients receiving guselkumab (73.3 percent) achieved a PASI 90 response, or near complete skin clearance,
compared with 2.9 percent of patients receiving placebo (P < 0.001)

PharmGPS Prediction: Guselkumab was rated as a molecule with a higher potenital than Humira
(as shown above) based on early phase III data and was later filed based on additional phase III
studies. The recent results of its superiority over Humira validate this analysis which was done
more than 1 year before the publication of these results.

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omecamtiv mecarbil Oral (CHF)

omecamtiv mecarbil Oral: Progresses to Phase III
(Segment: Stage C Heart Failure with reduced ejection fraction, Phase: Phase III,

Company: Cytokinetics Inc)
September 1st, 2016: Cytokinetics and Amgen to Advance Omecamtiv Mecarbil to Phase 3

Clinical Development

Performance Benchmark

enalapril

Xarelto

2.97, 2.7 3.1, 2.55 Enalapril 3 3
EFFICACY
omecamtiv mecarbil Oral 4.25, 2.65 SAFETY
SOC
2.5, 2.55

omecamtiv mecarbil Oral

Tekturna Omecamtive mecarbil oral

2.97, 1.35

SOC Phase II analysis Phase III analysis 22 22
EFFICACY SAFETY
Phase II analysis Phase III analysis

In September 2016, Cytokinetics, Inc. announced the advancement of omecamtiv mecarbil to Phase 3 clinical
development with a cardiovascular outcomes clinical trial. The decision to proceed to Phase 3 development
follows the review of results from prior clinical trials, including COSMIC-HF (Chronic Oral Study of Myosin Activa-
tion to Increase Contractility in Heart Failure), a Phase 2 clinical trial evaluating omecamtiv mecarbil in patients
with chronic heart failure. COSMIC-HF met its primary pharmacokinetic objective and demonstrated statistically
significant improvements in all pre-specified secondary measures of cardiac function in the treatment group
employing pharmacokinetic-based dose titration.

PharmGPS Prediction: In Phase II, PharmGPS predicted omecamtiv mecarbil as one of the top can-
didates for the treatment of congestive heart failure. Its progression to phase III validates
PharmGPS analysis based on early data.

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Radicava (Amyotrophic Lateral Sclerosis (ALS))

Radicava: Safe and effective treatment for ALS
(Segment :Mild to Moderate ALS, Phase: Approved, Company: Mitsubishi Chemical Holdings Corporation)

August 30th 2016: FDA Accepts New Drug Application for Potential ALS Treatment Edaravone

Performance Benchmark

Riluzole

Riluzole 3 3
EFFICACY
3.58, 1.85 SAFETY
Radicava Radicava SOC

2.825, 1.45 Radicava

mecobalamin
3.175, 1.55
tirasemtiv

SOC Phase II analysis Filed analysis 22 22
EFFICACY SAFETY
Phase II analysis Filed analysis

In August 2016, Mitsubishi Tanabe Pharma Corporation announced that the FDA has accepted the company’s
New Drug Application (NDA) for edaravone (MCI-186) an intravenous treatment for amyotrophic lateral sclerosis
(ALS). FDA and EMA has also granted Orphan Drug Designation for edaravone. Phase II study met its primary
efficacy endpoint of mean change in the ALS Functional Rating Scale-Revised (ALSFRS-R).

PharmGPS Prediction: PharmGPS identified Radicava as one of the front-runners for ALS and
FDA accepting to review it supports this prediction. Radicava may be effective at slowing the
progression of ALS and providing some disease reversal, particularly when used by those who
have had the disease for less than three years.

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Siponimod (MS)

Siponimod: Shows Promise in SPMS
(Segment: Secondary Progressive MS, Phase: Phase III, Company: Novartis AG)
September 17th, 2016: Novartis BAF312 reduces the risk of disability progression in pivotal phase III

study in secondary progressive MS patients

Performance Benchmark

Mitoxantrone

mitoxantrone 3 2
EFFICACY
2.975, 2 3.75, 2.45 SAFETY
SOC
Siponimod Masitinib

2.12, 2

Siponimod 2.57, 2

2.8625, 1.85

MD1003

Siponimod

SOC Phase II analysis Phase III analysis 33 11
EFFICACY SAFETY
Phase II analysis Phase III analysis

In September 2016, Novartis announced positive results of the Phase III EXPAND study showing that oral
once-daily BAF312 (siponimod) significantly reduced the risk of disability progression compared with placebo in
people with secondary progressive multiple sclerosis. Treatment with BAF312 reduced the risk of three-month
confirmed disability progression by 21% compared with placebo (p=0.013). The risk reduction for six-month
confirmed disability progression was greater, further supporting robustness of the data.

PharmGPS Prediction: According to PharmGPS, siponimod has been one of the most promising
assets in treating SPMS. The recent positive results validate this analysis. Since there are very few
available treatment options to delay disease progression in SPMS, siponimod may be the next
promising therapy for SPMS.

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Tecentriq (NSCLC)

Tecentriq: Receives FDA Approval (Segment:2nd Line therapy for PD-L1-positive NS-NSCLC Phase:
Approved; Company: Roche)October 19th 2016: FDA approves Roche’s cancer immunotherapy TECENTRIQ

(atezolizumab) for people with a specific type of metastatic lung cancer

Performance Benchmark

Keytruda

Tecentria
4.06, 3.4

4.31, 3.2 4 3
Keytruda EFFICACY
SAFETY
Tecentriq Bavencia SOC
2.71, 2.35 3.71, 2.1
Tecentriq

Opdivo + yervoy Tecentriq 34 22
3, 1.6 Approved analysis EFFICACY SAFETY
Phase III analysis Approved analysis
Keytruda Tecentriq
Phase III analysis

In October 2016 Roche announced that the FDA approved TECENTRIQ® (atezolizumab) for the treatment of
people with metastatic non-small cell lung cancer (NSCLC) who have disease progression during or following
platinum-containing chemotherapy, and have progressed on an appropriate FDA-approved targeted therapy if
their tumour has EGFR or ALK gene abnormalities. This approval is based on results from the randomised Phase
III OAK and Phase II POPLAR studies.OAK study, showed that TECENTRIQ helped people in the overall study
population live a median of 13.8 months, 4.2 months longer than those treated with docetaxel chemotherapy
(median overall survival [OS]: 13.8 vs. 9.6 months; HR = 0.74, 95% CI: 0.63, 0.87). The study enrolled people
regardless of their PD-L1 status and included both squamous and non-squamous disease types

PharmGPS Prediction: PharmGPS predicted Tecentriq as one of the front runners in PharmGPS.
Tecentriq can be considered as new option to help people with previously treated metastatic lung
cancer, regardless of PD-L1 expression, live longer than chemotherapy. With recent FDA approval,
PharmGPS validation has been validated.

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Upadacitinib (Rheumatoid Arthritis)

Upadacitinb : Progresses to Phase III
(Segment: Second line in Conventional DMARD resistant±MTX; Phase: Phase III) ; Company: Abbvie

January 8th 2016: AbbVie Announces the Launch of Robust Phase 3 Clinical Trial Program
Evaluating ABT-494, an Investigational Selective JAK1 Inhibitor, for the Treatment of Rheumatoid Arthritis

Performance Benchmark

Actemra

Upadacitinib 3 2
EFFICACY
Upadacitinib 3.23, 2.9 Actemra SAFETY
SOC
2.45, 2.9 3.75, 2.95

3.36, 2.2

Ravax Olokizumab

2.95, 1.85 Upadacitinib

SOC Upadacitinib Upadacitinib 23 23
Phase II analysis Phase III analysis EFFICACY SAFETY
Phase II analysis Phase III analysis

In January 2016, Abbvie announced the start of a large Phase 3 clinical trial program to study the use of ABT-494,
an investigational, once-daily, oral selective JAK1 inhibitor for the treatment of rheumatoid arthritis (RA).The trial
was initiated after the announcement of Phase II results, study demonstrated the efficacy of ABT-494 across 6,
12 and 18 mg doses twice-daily, and 24 mg once-daily in RA patients with an inadequate response to prior
anti-tumor necrosis factor (TNF-IR) or methotrexate (MTX-IR) treatment.

PharmGPS Prediction: PharmGPS rated upadacitinib (ABT-494) as one of the front runners in
PharmGPS based on early phase II data. The progression of this drug to next phase validates
PharmGPS analysis of the promise this drug holds.

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Xeljanz Modified release (Rheumatoid Arthritis)

Xeljanz XR : Approved by FDA
(Segment: First line in Conventional DMARD resistant+MTX; Phase: Approved; Company: Pfizer Inc
February 24th 2016: Pfizer Announces FDA Approval of XELJANZ® XR (tofacitinib citrate) Extended-Release

Tablets, the First and Only Once-Daily Oral JAK Inhibitor Treatment for Rheumatoid Arthritis

Performance Benchmark

Humira

Cimzia 3 2
EFFICACY
4.8, 2.9 SAFETY
SOC
3.8, 2.6

Xeljanz Xeljanz

3.4, 2.2 4.25, 2.6 Enbrel

Rituxan 4.8, 2.35

Xeljanz Modified

SOC Xeljanz Xeljanz 33 22
Phase III analysis Approved analy- EFFICACY SAFETY
Phase III analysis Approved analysis

In February 2016, Pfizer Inc. announced that the FDA has approved XELJANZ® XR (tofacitinib citrate) extend-
ed-release 11 mg tablets for the once-daily treatment of moderate to severe rheumatoid arthritis (RA) in patients
who have had an inadequate response or intolerance to methotrexate (MTX). Xeljanz XR met primary and
secondary endpoints.

PharmGPS Prediction: Xeljanz XR was predicted as one of the top molecules for RA by PharmGPS.
The recent approval of this drug validates the prediction made by PharmGPS based on phase III
data making it the first and only once-daily oral RA treatment in its class.

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XP23829 (Psoriasis)

XP23829 : Dr Reddy’s partners with Xenoport for psoriasis drug

(Segment: Severe Psoriasis; Phase: Phase II ); Company: Eli Lilly
March 16th 2016: Dr. Reddy’s Laboratories and XenoPort Enter into a U.S. Licensing Agreement for XP23829

Performance Benchmark

Humira

XP23829 4.675, 2.6 3 2
EFFICACY
3.05, 2.2 Humira SAFETY
SOC
Tregalizumab

2.2, 1.7

XP23829

CJM112

2.2, 2.8

SOC XP23829 Phase II 2015 and 44 33
Phase II 2016 analysis
EFFICACY SAFETY

Phase II 2015 Phase II 2015
analysis analysis

In March 2016, Dr. Reddy's Laboratories and XenoPort, Inc. announced that they have entered into a license
agreement pursuant to which Dr. Reddy’s Laboratories will be granted exclusive U.S. rights for the development
and commercialization of XenoPort’s clinical-stage oral new chemical entity, XP23829. Under the terms of the
agreement, Dr. Reddy’s Laboratories will receive exclusive U.S. rights to develop and commercialize XP23829 for
all indications. In 2015, Xenoport announced Phase II results. XP23829 met its primary endpoint in both 800 mg
once daily and 400 mg twice daily doses, demonstrating statistically significant improvements in percent change
from baseline to week 12 in Psoriasis Area and Severity Index (PASI) score

PharmGPS Prediction: In 2015, PharmGPS rated XP23829 as one of the top candidates for psoria-
sis based on early phase II data. With the licensing deal between Xenoport and Dr.Reddy’s, this
assessment has been validated.

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Baricitinib (Rheumatoid Arthritis)

BARICITINIB: SUPERIOR TO HUMIRA
(Segment: First line in Conventional DMARD resistant+MTX; Phase: Approved ; Company: Eli Lilly)
February 13th 2017: European Commission Approves Once-Daily Olumiant Tablets for Treatment of

Adults with Moderate-to-Severe Active Rheumatoid Arthritis

Performance Benchmark Humira

Baricitinib Baricitinib Humira 3 2
2.575, 3.15 3.15, 3.15 4.8, 2.8 EFFICACY
SAFETY
Sirukumab Tunex SOC
4.875, 2.5

3.6125, 2.3 Baricitinib

Zykadia Baricitinb Baricitinb 44 22
EFFICACY SAFETY
Phase III analysis Approved analysis Phase II analysis Approved analysis

In February 2017 Eli Lilly and Company and Incyte Corporation announced that the European Commission has
granted marketing authorisation for Olumiant ® (baricitinib) 4 mg and 2 mg film-coated tablets in Europe for the
treatment of moderate-to-severe active rheumatoid arthritis (RA) in adult patients who have responded
inadequately to, or who are intolerant to, one or more disease-modifying antirheumatic drugs (DMARDs). Approval
was based on five phase 3 clinical trials of baricitinib in adult patients with moderate to severe active rheumatoid
arthritis (RA-BEGIN, RA-BEAM, RA-BUILD, RA-BEACON and RA-BEYOND). A wide range of patients participated in
the clinical trial program, including those who are inadequate responders to methotrexate, inadequate responders
to conventional synthetic disease modifying anti rheumatic drugs (csDMARDs), or inadequate responders to
biological disease modifying anti rheumatic drugs (bDMARDs) including TNF inhibitors

PharmGPS Prediction: Baricitinib is the first JAK1/2 inhibitor approved to treat RA in the European
Union -- which may be used as monotherapy or in combination with methotrexate. In Phase II and
phase III, baricitinb showed promising data in patients with RA and was predicted as a promising
oral therapy for RA by PharmGPS. With the upcoming FDA approval baricitinb could undoubtedly
prove to be the best in class drug for RA

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Dupixent (dupilumab) (Atopic Dermatitis)

DUPIXENT: NEW HOPE FOR PATIENTS WITH ATOPIC DERMATITIS
(Segment: Moderate to severe Atopic dermatitis Phase: Approved ; Company: Regeneron Pharmaceutical-
sand Sanofi) March 28th 2017: Regeneron and Sanofi announce FDA approval of dupixent (dupilumab),

the first targeted biologic therapy for adults with moderate-to-severe atopic dermatitis

Performance Benchmark Elidel

Dupixent Elidel 2 3
2.95, 2.5 4.25, 2.75 EFFICACY
AMG0101 Dupixent SAFETY
2.562, 1.65 3.75, 2.5 SOC

Topicort Spray Filgotinib
3.675, 1.4

Elidel Dupixent Dupixent 33 22
EFFICACY SAFETY
Phase III analysis Approved analysis Phase III analysis Approved analysis

In March 2017 Regeneron Pharmaceuticals, Inc. and Sanofi announced that the FDA approved DUPIXENT (dupi -
lumab) Injection for the treatment of adults with moderate-to-severe atopic dermatitis (AD) whose disease is not
adequately controlled with topical prescription therapies, or when those therapies are not advisable. The approval
of DUPIXENT was based on data from the global LIBERTY AD clinical program, which included three randomized
Phase 3 pivotal trials known as SOLO 1, SOLO 2 and CHRONOS (enrolled 2,119 total adult patients). At 16 weeks,
for SOLO 1 and SOLO 2, respectively, 41 and 36 percent of patients who received DUPIXENT 300 mg every two
weeks achieved a greater than or equal to 4 point improvement in the daily intensity of patient-reported itch, com -
pared to 12 and 10 percent with placebo. In the CHRONOS study, study also met additional key secondary
endpoints at 52 weeks, showing that 36 percent of patients who received DUPIXENT 300 mg every two weeks with
TCS achieved clear or almost clear skin (IGA 0 or 1), compared to 13 percent of patients receiving placebo with
TCS

PharmGPS Prediction: Dupixent is the first and only targeted biologic approved for the treatment of adults
with moderate-to-severe atopic dermatitis (AD) and has also been granted Breakthrough designation by the
FDA. Dupilumab was rated as one of the promising molecules by PharmGPS based on early phase III
results. With recent filing and approval of Dupixent, the prediction has been validated.

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Keytruda + Alimta + Carboplatin (NSCLC)

Keytruda + Alimta + Carboplatin: Demonstrated a Near-Doubling of Objective Response Rate Compared to Standard of Care
Alone in First-Line Metastatic Non-Small Cell Lung Cancer(Segment:1st Line therapy for PD-L1-positive NS-NSCLC Phase:
Filed; Company: Merck)January 10th 2017; Merck Receives FDA Acceptance of Supplemental Biologics License Application for
KEYTRUDA® (pembrolizumab) in Combination with Chemotherapy for First-Line Treatment of Metastatic Non-Squamous

Non-Small Cell Lung Cancer

Performance Benchmark Keytruda

3.55, 3.5 Keytruda 4 3
4.685, 3.8 EFFICACY
SAFETY
2.265, 3.5 SOC

Keytruda + Alimta Keytruda + Alimta
+ Carboplatin Du3r.v1a1,lu3m.2 ab + Carboplatin

Kadcycla Keytruda + Alimta + carboplatin
2.2, 1.6

Keytruda Keytruda + Alimta Keytruda + Alimta + 34 22
+ Carboplatin carboplatin EFFICACY SAFETY
Phase II analysis Filed analysis Phase II analysis Filed analysis

In January 2017 Merck announced that the FDA has accepted for review the supplemental Biologics License
Application (sBLA) for KEYTRUDA® (pembrolizumab), plus chemotherapy (pemetrexed plus carboplatin) for the
first-line treatment of patients with metastatic or advanced non-squamous non-small cell lung cancer (NSCLC)
regardless of PD-L1 expression and with no EGFR or ALK genomic tumor aberration.In June Merck announced
results from Keynote-021 .The findings demonstrated that ORR nearly doubled with the pemetrexed-pembroli-
zumab-carboplatin combination, with an ORR of 55 percent (n=33/60), compared to 29 percent (n=18/63) for the
control arm alone (treatment difference 26%, 95% CI, 9-42% p=0.0016); all responses were partial. Median dura-
tion of response was not reached in either group (range, 1.4+-13.0+ for the pemetrexed-pembrolizumab-carbopla-
tin combination; 1.4+-15.2+ for the control arm). Responses in both groups were durable, with 88 percent
(n=29/33) of responders in the pemetrexed-pembrolizumab-carboplatin combination group and 78 percent
(n=14/18) of responders in the control arm group experiencing ongoing response at the time of data cut-off

PharmGPS Prediction: PharmGPS rated Keytruda + alimta + carboplatin as one of the promising
molecule even in phase II. With recent sBLA filing, this prediction has been validated as it has
proven to be effective in the first-line treatment of patients with metastatic non-small cell lung
cancer (NSCLC)

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Tildrakizumab (Psoriasis)

TILDRAKIZUMAB:
Segment: Severe Psoriasis, Phase: Filed , Company: Sun Pharmaceuticals)
March 24th 2017; Almirall and Sun Pharma Announce Regulatory Filing of Tildrakizumab in Europe

Performance Benchmark Humira

Risankizumab 3 2
3.45, 3.4 EFFICACY
SAFETY
4, 2.8 SOC

Tildrakizumab

3.4, 2.8 Tildrakizumab
4.45, 2.6

picledenoson Humira

2.825, 2.2 Tildrakizumab

Zykadia Tildrakizumab Tildrakizumab 23 22
EFFICACY SAFETY
Phase III analysis Filed analysis Phase II analysis Phase III analysis

In March 2017, Almirall and Sun Pharmaceutical Industries Ltd announced the Regulatory Filing of tildrakizumab
with the European Medicines Agency (EMA). The filing includes efficacy and safety data from the pivotal Phase III
clinical trials (reSURFACE 1 and 2) that included over 1,800 patients. In the trials, an average of 63 percent of
patients achieved 75 percent of skin clearance (Psoriasis Area Sensitivity Index or PASI 75) by week 12 after only
two injections, and 77 percent achieved 75 percent skin clearance after 28 weeks and three injections of the 100
mg dose of tildrakizumab (64 percent and 80 percent in reSURFACE 1, 61 percent and 74 percent in reSURFACE
2). Similarly, an average of 57 percent and 66 percent of patients had a Physician's Global Assessment (PGA)
score of "clear" or "minimal" with the 100 mg dose at weeks 12 and 28 respectively.

PharmGPS Prediction:. PharmGPS prediction has been validated by filing of tildrakizumab in
Europe for psoriasis as the drug was considered as one of the front runners both in phase II and
phase III analysis. Tildrakizumab may offer patients treatment for moderate to severe psoriasis
without burden of frequent infections.

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