Pipeline Analysis

A Product and Pipeline Analysis of the Lung

Cancer Therapeutics Market

January 2015

Discovery of New Targeted Therapies will Replace Conventional

Therapies

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Contents

Section Slide Numbers

Executive Summary 4

Methodology and Scope 8

Market Overview 10

Segmentation 11

Recent Market Developments 14

Companies to Watch 15

Key Merger, Acquisition, and Partnership Assessment 16

Game-changing Strategies 17

Epidemiology 18

Competitive Landscape 22

Timeline of Product Launches/Approval 25

Timeline of Patent Expiries 26

Competitive LandscapePivotal Clinical Trials 27

Marketed Products 29

Marketed Products Synopsis 30

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Section Slide Numbers

Pipeline Drugs Analysis 34

Pipeline Synopsis 35

Product Dashboard of Recently Approved Drugs and Late-stage Pipeline Drug

Candidates 52

Conclusions 61

Appendix 64

The Frost & Sullivan Story 67

Contents (continued)

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The estimated market size for lung cancer therapeutics in 2014 was $ billion.

There is increasing competition in this market, especially amongst the large pharmaceutical (pharma)

participants such as Merck, AstraZeneca, Eli Lilly, and Bristol-Myers Squibb (BMS), which are set to

launch their targeted therapy drugs.

BMS has already launched Opdivo (Nivolumab) in Japan (July 2014), and became the first company to

introduce its candidate in the PD-L1 pathway.

Other mutations found in non-small cell lung cancer (NSCLC) such as EGFR ( %*), ALK ( %*),

BRAF ( %*), HER ( %*), and KRAS ( %*) have only a few drugs in the pipeline.

EGFR and ALK are the only two mutations that have FDA-approved drugs in the market.

Two drugs targeting the ALK mut+ population are in the pipeline and have been given breakthrough

therapy status by the Food and Drug Administration (FDA).

Having faced failure as a potential target for a long time, KRAS mut+ NSCLC now has drugs in Phase-2

development.

Squamous NSCLC, which constitutes % of lung cancer patients worldwide, remains a condition with

largely unmet needs due to the existence of very few approved targeted therapies for its treatment.

Similarly, there is only one FDA-approved drug for third-line treatment of lung cancer, which is Tarceva.

Sources: Lovly, C., L. Horn, W. Pao. 2014. Molecular Profiling of Lung Cancer; Frost & Sullivan

*Frequency of mutations in NSCLC patients

EGFR: Endothelial Growth Factor Receptor

ALK: Anaplastic lymphoma kinase

HER: Human Epidermal growth factor Receptor

Executive Summary

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Source: www.lung.org; www.cancer.org; JAMA. 2014;311(2):183-192. doi:10.1001/jama.2013.284692.; WHO; Frost & Sullivan

Executive Summary (continued)

First-line treatment consists of administering the usual chemotherapy, i.e., platinum agent plus

Gemcitabine, or Paclitaxel. However, this might change with the introduction of necitumumab, Eli Lillys

candidate at present in Phase 3 of clinical trials in the United States.

Other drugs such as Yervoy and nivolumab are also being tested in clinical trials as targeted therapy for

squamous NSCLC.

With a heavy pipeline of about drugs in Phase-2 clinical trials, and most Phase-3 drugs showing

effective results, a number of launches are expected by 2020.

Tobacco consumption is the main cause of lung cancer worldwide, with approximately % of the

patients being smokers. Recent statistics show that % of adults in China smoke regularly, and almost

one in two men consume cigarettes regularly.

o In addition, a less proactive take by the Chinese Government in raising lung cancer awareness

contributes to making China the highest-growing market for lung cancer therapeutics today.

A number of niche participants such as BioNumerik Pharmaceuticals, Ora Bio, Simcere Pharmaceutical

Group, Peregrine Pharmaceuticals, RECOMBIO, Oncothyreon Inc., Tesaro Inc., Exelixis Inc., CureVac

GmbH, Clovis Oncology, ArQule, NewLink Genetics Corporation, and Synta Pharmaceuticals have

drugs in Phase 2 or Phase 3 in the pipeline for lung cancer treatment.

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Alkaloids Cytostatics Anti-neoplastic MAb Others

1st-line

Therapy

Abraxane (locally advanced or

metastatic NSCLC)

Camtobell Injection (SCLC)

Etopophos Preservative Free

(SCLC)

Navelbine (advanced NSCLC)

Xalkori (advanced NSCLC)

Gilotrif (metastatic NSCLC)

Iressa (advanced NSCLC)

Avastin (advanced non-squamous

NSCLC)

Gemzar (locally advanced or

metastatic NSCLC)

Alimta (locally advanced or

metastatic non-

squamous NSCLC)

2nd-line

Therapy

Docetaxel (advanced NSCLC)

Hycamtin (SCLC)

Tarceva (metastatic NSCLC)

Iressa (advanced NSCLC)

ZykadiaTM (ALK-positive metastatic

NSCLC)

Methotrexate (SCLC and NSCLC)

Alimta (locally advanced or

metastatic non-

squamous NSCLC)

3rd-line

Therapy

Tarceva (metastatic NSCLC)

Source: Frost & Sullivan

Lung Cancer Therapeutics Market: Marketed Products, Global, 2014

Only FDA-approved drug for

3rd-line treatment Note: There are no marketed products under anti-angiogenics

SCLC: Small Cell Lung Cancer

Executive Summary (continued)

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This research service focuses on the prescription drugs used for the treatment of both non-small cell

lung cancer (NSCLC) and small cell lung cancer (SCLC). It does not cover non-pharmaceutical

palliative therapies such as radiation and surgery.

A product and pipeline assessment is provided for marketed and investigational products for the

treatment of NSCLC and SCLC. Segmentation by drug class is provided, along with additional

supporting information such as clinical trial timelines and results, projected launch timelines, and

epidemiology.

The information contained in this research service was derived from published sources, including

disease organization Web sites; public health organization Web sites; company publications including

annual reports, SEC filings, and press releases; government public sources; and published articles in

scientific journals.


Methodology and Scope

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Lung Cancer Therapeutics

Lung Cancer Therapeutics Market: Segmentation, Global, 2014

Alkaloids Other

Therapies*

Alkaloids are nitrogen-containing basic compounds mainly derived from animal and plant sources. Various alkaloids are used as therapeutic agents to inhibit cell reproduction;

sometimes, they may even kill the cancerous cells. E.g., Abraxane

Cytostatics inhibit the proliferation of cells. In other words, these compounds inhibit the cancerous cells from growing, without killing them. Most cancer drugs fall into this category.

Anti-angiogenics, or angiogenic inhibitors, are the class of cancer drugs that stop the growth of new blood vessels in cancerous tumours, thereby stopping their nourishment and

their spread to other parts of the body.

Anti-neoplastics, also know as anti-neoplastic chemotherapeutic drugs, destroy neoplastic cells in the body, which accumulate to form the cancerous tumours. However, they have the

side-effect of destroying normal cells as well, thereby leaving the patient weak.

Cytostatics


Anti-

Angiogenics Anti-Neoplastic

*Other pharmacological approaches include bone calcium regulators, cytotoxic antibiotics, anti-cancer agents,

immunostimulants, anti-rheumatics, alkylating agents, and anti-metabolites.

Market OverviewSegmentation

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Other Therapies*

o Bone-calcium regulators do not treat the disease but are used in cases where the

cancer has metastasized to the bone, leading to fractures and pain.

o Cytotoxic antibiotics work by interfering with the DNA but do not directly lead to

apoptosis and are sufficient for the bodys immune system to recognize and kill the cells.

o Anti-cancer agents selectively target cancer cells by detecting their altered

metabolism from the normal cells in the body.

o Immunostimulants positively regulate the bodys immune system to fight the abnormal, cancerous cells.

o Anti-rheumatics act by stopping the recruitment of lymphocytes during inflammation

in rheumatoid arthritis and, in case of cancer, towards the tumour.

o Alkylating agents are the oldest form of treatment for cancer. These drugs add an

alkyl group to the DNA of cancerous cells, thereby hampering cell growth.

o Anti-metabolites disrupt the biosynthesis of nucleic acids, essential for the formation

of DNA and RNA, thus leading to cell death.


Market OverviewSegmentation (continued)

Lung Cancer Therapeutics Market: Segmentation, Global, 2014



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Cytostatics %

Anti-angiogenics %

Anti-neoplastics %

Alkaloids %

Other therapies %


Market OverviewSegmentation (continued)



Lung Cancer Therapeutics Market: Percentage Distribution of Marketed and Pipeline Drugs,

Global, 2014

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Date Type of Event Description

October 2014 Clinical development Ariad Pharmas AP26113 gets breakthrough status from the US FDA for its treatment of lung cancer in patients who did not respond to crizotinib.

October 2014 Mergers and

collaborations

Bristol-Myers and Novartis collaborate to study the investigational drug developed by the

former targeting of the PD-1 pathway, Opdivo (nivolumab).

October 2014 Clinical development

AstraZeneca presents positive results for its 3 on-going clinical trials on drugs AZD9291,

MEDI4736, and a combination therapy of MEDI4736 and tremelimumab at the European

Society of Medical Oncology 2014 (ESMO).

September 2014 New Drug Approval BMSs nivolumab is the first drug in line for an EMA approval for lung cancer treatment based on the blocking of PD-1 pathway that allows undetected growth of cancerous cells.

September 2014 Mergers and

collaborations

CureVac signed a $ million deal with Boehringer Ingelheim, providing commercial rights to the latter for CureVacs investigational lung cancer vaccine, CV9202.

September 2014 Clinical Development Results from Phase 2 of Pfizers drug Xalkori (crizotinib) for lung cancer patients with a rare ros1 gene mutation proved that the drug was effective in shrinking the tumour

September 2014 Patent law

infringement

BMS and Ono Pharmaceutical Co. filed a patent infringement case against Merck Co.

regarding their latest anti-cancer drug, Keytruda, on the mechanism developed by BMS

and Ono that harnesses the bodys immune system to fight cancer.

August 2014 Clinical development

OncoMeds monoclonal antibody candidate, OMP-18R5, is under Phase-1b trials after the FDA lifted its partial clinical hold on the drug for mild-to-moderate bone-related

problems.

Lung Cancer Therapeutics Market: Market Developments, Global, Q2Q4 2014


Recent Market Developments

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Ariad Pharmaceuticals

AP26113 received breakthrough therapy status from the FDA in October 2014. Ariad plans to file the drug with the FDA in early 2016.

Ariads share rose by % immediately after the FDA gave AP26113 breakthrough therapy status.

AstraZeneca

Has drug candidates in the pipeline (Phase 2 and Phase 3), and one marketed product (Iressa) for lung cancer treatment.

Plans to file AZD9291 for approval with the FDA in Q2 2015; this is one of the leading products for lung cancer R&D in the market.

MEDI4736, a drug targeting the PD-1 pathway, recently entered Phase-3 clinical trials.

Roche Group

Has 2 marketed products and 4 drugs in Phase 3 of clinical trials for lung cancer. Launched a Web site and a mobile app for lung cancer support and awareness in

May 2014: www.pioneeringhealthcare.com/lung-cancer/

Alecitinib, which targets ALK+ NSCLC, was approved for marketing in Japan in July 2014. It already has breakthrough therapy designation from the FDA.

Eli Lilly and Company

Has 2 marketed, 2 filed with the FDA for approval, and 3 drugs in the pipeline (Phase 1 and Phase 2).

Necitumumab has the potential to be the first targeted therapy for first-line treatment of squamous NSCLC.


Companies to Watch

Documents

Pipeline Analysis