An high-level overview : The overall objective is to prioritize solid tumors with pan-FGFR driven cancer, evaluate clinical benchmarks and develop TPP for lead indication - Ashish Jaiswal | Email: ashish.jaiswal8@gmail.com

1. Deck Summary
✓ Brief outlook – Solid tumors – Illustrative only
✓ Priority for top three solid tumors
✓ Clinical benchmarks
✓ Target Product Profile (TPP) for lead indication
Ashish Jaiswal
Senior Management Consultant at IQVIA, Gurgaon
June 2021

2. 1
Overall objective is to prioritize solid tumors with pan-FGFR driven cancer,
evaluate clinical benchmarks and develop TPP for lead indication
Detailed objectives
Priority for top three solid tumors
• To briefly review the rationale behind the development of a targeted therapy
centred in FGFR
• Understand the incidence and disease burden on solid cancer patients
population
• Identify key clinical benchmarks for clinical development decisions
Target Product Profile (TPP) • Develop TPP for the target indication
Case study
• A global pharma company has a pan-FGFR targeting small molecule that is under evaluation in Phase I in solid tumors. They now want a
comprehensive analysis in order to make well-informed clinical development decisions on which tumors to pursue and what clinical
benchmarks will be required to differentiate the asset in the top three tumors.
Target TA Oncology Solid Tumors FGFR Inhibitors
Scope
• Provide a stepwise approach to prioritize the top three tumors and develop a Target Product Profile for recommend lead indication
Abbreviation: FGFR - Fibroblast Growth Factor Receptor

3. 2
Global burden of cancer is set to increase over 50% by 2040, from 19 million
new cases in 2020 to nearly 29 million cases in 2040
Solid Cancer Type Incidence (2020) Solid Cancer Type Mortality (2020)
Breast cancer 2.3 million (11.7%) Lung cancer 1.8 Mn (18%)
Lung cancer 2.2 million (11.4%) Colorectal cancer 0.93 Mn (9.4%)
Colorectal cancer 1.9 million (10.0 %) Liver cancer (HCC) 0.83 Mn 8.3%
Prostate cancer 1.4 million (7.3%) Stomach cancer 0. 77 Mn (7.7%)
Stomach cancer 1.08 million (5.6%) Breast cancer 0.68 Mn 6.9%
Liver cancer 0.90 million (4.7%) Oesophagus 0.54 Mn 5.5%
Globally, an estimated ~19 Mn new cancer cases and nearly 10.0 Mn cancer deaths occurred in 2020. Deaths
due to Lung cancer is highest at ~1.8 Mn (18%) followed by Colorectal and Liver cancer
GLOBOCAN 2020 estimates of cancer incidence and mortality
Source: GLOBOCAN 2020
Lung, 18%
Colorectum,
9.4%
Liver, 8.3%
Stomach,
7.3%
Breast,
6.9%
Oesophagus, 5.5%
Other
cancers,
39.5%
Worldwide estimated deaths in 2020
87
Countries reported Lung
cancer as leading cancer
death. Primarily, Europe,
the US and Canada shows
high mortality rates
HCC is the 3rd
leading cause of
cancer death
worldwide
Most common
malignancy in the
U.S. is bladder
cancer
3rd
4th
Abbreviation: HCC- Hepatocellular carcinoma

4. 3
Precision oncology relies on the identification of molecular alterations, as a
suitable targets for specific inhibitors
Tyrosine
kinase
receptors
Amplified (A) Mutation (M) Fusion (F)
FGFR – 1
Lung Cancer (17%), Breast
Cancer (19%)
FGFR - 2
Breast Cancer (4%), Colon
and Gastric Cancer (~10%) Endometrial cancers (10%),
Bladder Cancer – urothelial
carcinoma (60%)
Liver Cancer
(45%), HCC(5%)
FGFR - 3
FGFR - 4 Colon Cancer, Liver Cancer
• Cases with gene fusions and mutations have shown better clinical
responses
• 1FGFR inhibition with gene amplifications do not show significant
clinical efficacy (less anti tumors activity reported)
• Clinical analysis have shown strong results for FGFR-3 target for
bladder cancer and FGFR-2 for cholangiocarcinoma
Predictive biomarker: Patients with FGFR driven alteration in solid cancer types are potential candidate
However, FGFR gene fusions (including mutations) have
emerged as a significant target for therapy
Biological plausibility
for solid cancer
driven by FGFR
Source: FGFR Inhibitors Clinical Evidence Report by Valdecilla Institute 2019, 1 ESMO Oncology News, March 2021
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5. 4
Molecular profiling of FGFR aberrations to target solid cancer type in clinical
setting
Note: The above shown illustration is on the basis of report
published - The FGFR Landscape in Cancer: Analysis of
4,853 Tumors by Next-Generation Sequencing
S.No Solid Cancer Type
FGFR
Aberrations
Top solid
tumors
1
Urothelial cancer
(M)
32%
2
Breast cancer
(A)
18%
3
Endometrial cancer
(M)
13%
4
Ovarian cancer
(A)
9%
5
Glioma
(M)
8%
6
Cholangiocarcinoma
(F)
7%
Frequencies and distributions of FGFR aberrations for all cancers Selection of top solid tumours…
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Qualifies for clinical investigation for solid tumors driven by FGFR
aberrations (Fusion/mutation)
Selection of gene amplification induced cancer may lead to poor
clinical responses
FGFR aberrations found in
~7% of all cancers

6. 5
While FGFR-3 driven mutations in urothelial carcinoma presents potential
opportunity for the target therapy…
Source: The Oncologist, Volume: 25, Issue: 11, Pages: e1711-e1719, First published: 13 August 2020, DOI: (10.1634/theoncologist.2020-0334)
FGFR3 alterations offers potential opportunity for the treatment of
urothelial cancer
• In urothelial carcinoma, FGFR3 alterations have been
documented in nearly 60% of low-grade noninvasive urothelial
carcinoma and 26.7% of overall urothelial carcinoma
• The incidence in upper tract high grade urothelial cancer is
35.6%
• Of the FGFR3 alterations seen in patients with urothelial
cancer, base substitutions are most common (84%)
• S249C, the most common mutation in bladder urothelial cancer
• Other notable mutations commonly observed are FGFR3-
TACC3 fusion
…Cholangiocarcinoma has emerged as another key target
of FGFR-2 inhibitor research

7. 6
Clinical measures for Pan-FGFR inhibitors
Primary Clinical End Points
✓ Dose Limiting Toxicities (DLTs)
✓ Participants experiencing adverse events
✓ Cmax (Maximum Drug Concentration in Plasma)
✓ Cmax/D (Maximum Drug Concentration in Plasma Divided by Dose)
Clinical study parameters for evaluation of FGFR inhibitors in solid tumors
Secondary End points
✓ Overall Response Rate (ORR)
✓ Duration of Response ( DOR)
✓ Time to Response (TTR)
✓ Evaluate Disease Control Rate (DCR)
✓ Progression Free Survival (PFS)
✓ Overall Survival (OS)
✓ Clinical Objectives – Measure to determine the safety, tolerability and maximum tolerated dose (MTD)
✓ Key clinical outcome measures includes:

8. 7
Most of the FGFR inhibitors under clinical development are focused on
urothelial cancer and cholangiocarcinoma
Agents under
Investigation
Target Ongoing Trials Mechanism of Action (MOA) Biomarker and Study Cohort
Regulatory Approvals
(US FDA)
Infigratinib
(BGJ 398)
FGFR 1-3 Phase III
ATP-competitive FGFR 1–3 tyrosine
kinase inhibitor
Urothelial carcinoma after 1st
and 2nd line of therapy
Approved for metastatic
cholangiocarcinoma
Erdafitinib
(JNJ42756493)
FGFR 1-4 Phase III FGFR 1–4 tyrosine kinase inhibitor
Uresectable or metastatic
Urothelial cancer
Approved for Urothelial
carcinoma as the 1st
targeted therapy.
Pemigatinib
(INCB053828)
FGFR 1-3 Phase III Selective inhibitor of FGFR1–3
Metastatic or unresectable
Urothelial cancer
Approved for
cholangiocarcinoma
Rogaratinib
(BAY 116387)
FGFR 1-3 Phase III Selective FGFR1–4 inhibitor
Overexpression of tumor FGFR
1–3 mRNA; advanced urothelial
cancer progression after
standard of care treatment
Derazantinib
(ARQ 087)
FGFR 1-4 Phase II Multikinase inhibitor of FGFR 1–3 Urothelial cancer
TAS-120 FGFR 1-4 Phase II
Selective irreversible inhibitor for
FGFR 1–4
Breast cancer, Bladder cancer,
primary CNS tumor, and
Gastroesophageal cancer
Debio-1347 FGFR 1-3 Phase II ATP binding site of FGFR1–3
Breast Cancer, Gastric,
Prostate, cervical cancer
Vofatamab
(B-701)
FGFR3 Phase II Selective anti- FGFR3 receptor Metastatic urothelial cancer
Gunagratinib
(ICP-192)
FGFR gene
aberrations
Phase I/II Selective pan-FGFR inhibitor
Anti-tumor activity for multiple
tumor types, including
cholangiocarcinoma
Approved for multiple tumors
including
cholangiocarcinoma
Summary of FGFR inhibitors with results in urothelial cancer and cholangiocarcinoma
Source: Pharmabiz News and other press releases accessed as on 27 June 2021 **Non exhaustive list
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9. 8
Target Product Profile for Pan FGFR for treatment of solid tumor
(Urothelial cancer) – (1/2)
Target Product Profile: Erdafitinib (JNJ42756493)
Indication
▪ Treatment of adult patients with locally advanced or metastatic urothelial
carcinoma (mUC)
▪ Harboring a prespecified FGFR3 mutation or FGFR2/3 fusion
Description and Mechanism of Action (MOA) ▪ Oral formulation with potent FGFR 1-4 tyrosine kinase inhibitor
Efficacy
Primary endpoint
▪ To compare Overall Survival (OS) among FGFR+ mUC patients treated with
Erdafitinib and FGFR+ mUC patients treated with currently available treatment
options, i.e., anti-PD-(L)1 and/or chemotherapy
Secondary endpoint
▪ To compare OS among FGFR+ patients treated with Erdafitinib with mUC
patients treated with anti-PD-(L)1, regardless of FGFR status
Other outcomes ▪ The maximum tolerated dose as determined
Safety and Tolerability
▪ Erdafitinib shows tolerability and preliminary evidence of clinical activity in
advanced solid tumors, at 2 different dosing schedules and with particularly
encouraging responses in UC and CCA
Dosing
▪ 8 mg orally once daily for 28 days on a 28 day cycle (with option to increase to
9 mg intermittent dosing based on phosphate level)
Adverse Dug Reactions
▪ The most common (incidence ≥ 20%) adverse reactions were
hyperphosphatemia, increased creatinine, nail toxicity, stomatitis, dry eye,
fatigue, alopecia, arthralgia, dysgeusia, constipation, abdominal pain, dry
mouth, eyelash changes, diarrhea, dry skin, decreased appetite, vision blurred
and vomiting
Illustrative only

10. 9
Target Product Profile for Pan FGFR for treatment of solid tumor
(Cholangiocarcinoma ) – (2/2)
Target Product Profile: Gunagratinib
Indication ▪ Pan-FGFR inhibitor for the treatment of cholangiocarcinoma
Description and Mechanism of Action (MOA)
▪ Highly selective pan-FGFR inhibitor with covalent binding targeting multiple
solid tumors with FGFR gene aberrations
Efficacy
Primary endpoint
▪ Overall response rate (ORR) was 33.3% with disease control rate (DCR) of
91.7%
Secondary endpoint
▪ Cmax, AUC, apparent half-life for designation elimination phases, food effect,
disease control rate (DCR), duration of objective response (DoR), progression-
free survival (PFS), and correlation between FGFR aberrations with efficacy
Other outcomes
▪ The maximum tolerated dose has not been reached. For patients with
FGF/FGFR gene aberrations who have completed at least 1 tumor
assessment, the ORR was 33.3%
Safety and Tolerability
▪ Safe and well-tolerated in patients with advanced solid tumors
▪ The maximum tolerated dose (MTD) had not been reached
Dosing
▪ The starting dose level was 2 mg. Patients received the agent once daily in 21-
days cycles until unacceptable toxicity or progression
Adverse Dug Reactions
▪ More than 20% of the patients, included hyperphosphatemia, hypercalcemia,
increased ALT or AST, diarrhea and hypertriglyceridemia.
▪ Hyperphosphatemia is commonly associated with other trials targeting FGFR.
It also serves as a PD biomarker of FGFR inhibition.
Illustrative only
Note: On the basis of Phase 1 report published

11. 10
FGFR has potential targeted therapy in FGFR-2 fusion and FGFR-3 mutation,
shows favorable clinical evidence for bladder and HCC
• FGFR inhibitors seems to be a successful “targeted therapy” in some cancers
• The most robust clinical data is in advanced urothelial cancers and cholangiocarcinoma as clinical studies have
demonstrated favorable safety profiles with significant antitumor activity
• The discovery of FGFR activating molecular alterations mainly FGFR-3 mutations and FGFR-2 fusions across many
tumor types, mainly urothelial cancer and intrahepatic cholangiocarcinomas, widens the selection of patients benefits
from selective FGFR inhibitors
• Despite this initial excitement some limitations apply to FGFR inhibitors such as DOR, low prevalence of FGFR
aberrations and safety profile compared with other treatment strategies in competitive environment
• There are multiple ongoing studies in the randomized setting that will more precisely define the real value of FGFR
inhibitors either alone or in combination
Conclusion and Key takeaway
Abbreviation: HCC - Hepatocellular carcinoma

12. 11
Ashish Jaiswal
Comes with 10+ years of industry experience and has been
an asset to the organizations employed
He is certified Six sigma Green Belt (ASQ), EY data
analytics bronze level, and a trained project management
professional
Three qualities makes him a good bet –
* Meets project deadlines * Deliver what is promised * As a
result, have always made his managers look good
Professional Memberships: India Pharmaceutical
Association; TIE Delhi and TIE Global
He is also a IPF-CCE certified coach and upcoming author
for “Your Success Blueprint”
Current location: Gurgaon
Open for
Q&A
Organizations served