Drivers of M&A in 2013-2016: PI3Ks and BTK Inhibitors

Targeting kinases have been on the agenda of most drug developers/ researchers as they hold the key path to signaling, development and growth of the cell. Tumors/cancer biology indicates that this balance is disturbed and inhibiting the aberrant pathways in a balanced way is an approach to developing drugs against cancer. Resistance to existing therapies develops as cancer cells bypass these efforts and there remains an evergreen search for new targets to meet these challenges. Large global pharma are constantly on the hunt for drugs with label expansion potential = Longevity and Blockbuster Potential! About $10b+ has already been invested in licensing /acquisition of PI3K and other kinase inhibitors/companies since the last five years. Scientific data on the role of PI3K, BTK kinase in cancer and clinical Proof of Concept (PoC) data of the PI3K, BTKs inhibitors have reached a critical mass and companies with focus in this sector are poised to offer better treatment options for unmet need in hematologic malignancies. We expect more acquisitions of the innovator companies and or handsome licensing deals for unpartnered products as mature data and approvals come in the next few years.

This report (ToC attached) highlights the recent progress on the understanding of PI3Ks/BTK signaling pathway and companies developing PI3K/BTK inhibitors (PCYC, INFI, CRIS, SymBio, GILD), the clinical data and competition.

KEY POINTS DISCUSSED IN THE REPORT
1. Drugs in the pipeline
• PI3K inhibitors – Infinity pharma (INFI), Gilead (GILD)
- Dual PI3K inhibitor – Onconova/SymBio, Curis (CRIS)
• BTK-inhibitors – Safety and clinical efficacy set it apart – Pharmacyclics (PCYC), Celgene (CELG)

2. M&A in Kinase Inhibitors in the last 5 years

3. Related Milestones/catalysts in 2013-14

4. Combination Studies – PI3K, BTK inhibitors with Rituxan, Bendamustine in hematological cancers.

5. Ongoing Clinical Trials of Companies Covered

6. Detailed Reports on –
- Curis (CRIS) – Time to Assess Value Beyond Erivedge!
- Gilead (GILD) - New HIV + HCV Products to Sustain the Growth Trajectory
- Infinity pharma (INFI) – IPI-145, Unpartnered, Potent PI3K Inhibitor = Larger Opportunity!
- Pharmacyclics (PCYC) – Ibrutinib - Promising to Deliver More
- SymBio (4582) - Significant Upside still Remains: Bendamustine + Rigosertib + Cash to In-license More!

1. Executive Summary

2. Drugs in the Pipeline
2.1 Phosphoinositide 3-Kinases (PI3Ks) inhibitors
a Scientific Rationale
b Dual inhibitors
2.2 Bruton’s Tyrosin Kinase (BTK) Inhibitors
a Scientific Rationale
b BTK inhibitors – Pipeline

3. M&A to Follow – Kinase inhibitors have attracted partnering deals at a premium
3.1 Kinase Inhibitor: Select M&A / Deals

4. Upcoming Milestones Related in 2013-14

5. Combination Studies – PI3K, BTK + Rituxan/ Bendamustine
5.1 Idelalisib (GS-1101) – Clinical Data
5.2 Rigosertib – Clinical Data
5.3 Other PI3K or Dual Inhibitors – Clinical Data
5.4 Combination Studies of PI3K and BTK Inhibitors

6. Ongoing Trials of PI3K and BTK Compounds

7. Company Analysis
7.1 Curis (CRIS) – Time to Assess Value Beyond Erivedge!
a Investment Drivers
b Multiple Catalysts in 2013 from Other products in Pipeline
c Background
• Erivedge (vismodegib, GDC-0449/RG3616)
• CUDC 907 (PhI, PI3K/HDAC dual Inhibitor)
• Other Drugs in Pipeline

7.2 Gilead – New HIV + HCV Products to Sustain the Growth Trajectory
a Investment Drivers
b Upcoming Milestones
c Clinical Update on HIV and HCV programs
d Beyond Anti-virals’ opportunity – Idelalisib
e Recent Acquisitions of YM Biosciences and MacroGenics

7.3 Infinity Pharma – IPI-145, Unpartnered, Potent PI3K Inhibitor =Larger Opportunity!
a Investment Drivers
b IPI-145 Potential Not Dimmed Even As a 3rd/4th Entrant
c IPI-443 (PC, PI3K-δ,γ inhibitor) Maximizing Value of PI3K-δ,γ Franchise
d Retaspimycin (PhII, heat shock protein 90, HSP90, NSCLC)
e Background
f Collaborations – Takeda/Millenium and Mundipharma and Purdue
g Retaspimycin hydrochloride (IPI-504, PhII)

7.4 Pharmacyclics – Ibrutinib – Promising to Deliver More
a  Investment Drivers
b  Best-in-Class among Leukemia Drugs – Durable efficacy in Naïve (TN) and Refractory (R/R) CLL and MCL pts as a monotherpay and in combination = Mega buster sales potential
c  Potential of Other Pipeline Drugs is yet to Unfold
d  Promising Signs of Ibrutinib
e  Clinical Data and Ongoing Trials
• Treatment-naïve & R/R CLL/SLL including pts with High Risk
• Non-Hodgkin Lymphoma (NHL)
• Diffuse Large B-Cell Lymphoma (DLBCL)
• Follicular Lymphoma (FL) and Multiple Myeloma (MM)
f  Ibrutinib for Autoimmune Disease
g  Beyond Ibrutinib
• Abexinostat (PCI-24781, partnered with Servier for Ex-US) – A Pan-HDAC Inhibitor
• Factor VIIa inhibitor: PCI-27483

7.5 SymBio – Significant Upside still Remains: Bendamustine + Rigosertib + Cash to In-license More!
a Investment Drivers
b Upcoming Milestones and Pipeline Update
c Clinical Data – Rigosertib, Bendamustine, and Combination Studies