Research and Development at Sun Pharma (PowerPoint)

Document Sample
Research and Development at Sun Pharma (PowerPoint) Powered By Docstoc
      September 2008
          Except for the historical information contained herein, statements in
          this presentation and the subsequent discussions, which include
          words or phrases such as “will”, “aim”, “will likely result”, “would”,
          “believe”, “may”, “expect”, “will continue”, “anticipate”, “estimate”,
          “intend”, “plan”, “contemplate”, “seek to”, “future”, “objective”,
          “goal”, “likely”, “project”, “should”, “potential”, “will pursue” and
          similar expressions or variations of such expressions may constitute
          "forward-looking statements". These forward-looking statements
          involve a number of risks, uncertainties and other factors that could
          cause actual results to differ materially from those suggested by the
          forward-looking statements. These risks and uncertainties include,
          but are not limited to our ability to successfully implement our
          strategy, our growth and expansion plans, obtain regulatory
          approvals, our provisioning policies, technological changes,
          investment and business income, cash flow projections, our exposure
          to market risks as well as other risks. Sun Pharma Advanced
          Research Company Limited does not undertake any obligation to
          update forward-looking statements to reflect events or circumstances
          after the date thereof.

Investor Presentation / 2
                                    BOARD OF DIRECTORS

      Mr. Dilip S. Shanghvi, Chairman & Managing Director
      Dr. T. Rajamannar, Director & Executive VP (R&D)‫‏‬
      Mr. Sudhir V. Valia, Director

     Independent Directors
      Prof. Dr. Andrea Vasella
      Prof. Dr. Goverdhan Mehta
      Mr. S. Mohanchand Dadha

Investor Presentation / 3
                                         NCE Pipeline

 Sun-1334H : An anti-allergic
 Sun-461 : An anti-inflammatory molecule for use in the
  treatment of asthma and COPD
 Sun-44 : A prodrug of gabapentin
 Sun-09 : A prodrug of marketed muscle relaxant

      Route of administration : Oral
      Broad therapeutic area : Anti-allergic disorder
      Treatment of
            Seasonal allergic rhinitis
            Perennial allergic rhinitis
      Current status
            Phase I completed in India and Europe
                127 human exposure
            Phase II ongoing in US
            Chronic toxicity studies ongoing

Investor Presentation / 5

      Mechanism of action
            Selective histamine H-1 receptor antagonist
            Poor or no affinity for other relevant receptors
      Summary of findings from clinical studies
            Once-a-day dosing
            Faster onset of action (within 30 minutes)‫‏‬
            Efficacy comparable to Cetrizine over a period of 24 hours
             on wheal and flare model
            No cardio toxicity seen
      Estimated Phase III beginning : 2008

Investor Presentation / 6

      Current global market size : USD 5.5 billion
      Opportunity : Patents expiring on competing products
      Challenge : Justify premium on competing generic
            Will need significant investment in studies to prove

Investor Presentation / 7

      Route of administration : Inhaler
      Broad therapeutic area : Anti-inflammatory
      Indications
      Mechanism of action
            Glucocorticoid receptor agonist
            Suppresses inflammatory response with significantly
             reduced systemic side effects
      Current status
            Pre-clinical studies ongoing
            Acute toxicity studies ongoing
            Phase I human studies exposure likely to begin in 2008
Investor Presentation / 8

                            Inactive Metabolite Approach
       Classical                                                 “Soft”
                                   Anti-inflammatory         Corticosteroid
 Anti-inflammatory                                               Activity

       Systemic                                               Inactivation
      Side Effects

                                                           Reduced Systemic
                                                              Side Effects
        & Excretion
                                                              & Excretion

Investor Presentation / 9

       Summary findings / data from studies completed *
                 Anti-inflammatory activity comparable to marketed
                 Side-effect profile superior
                    In Sephadex-induced lung edema model, therapeutic index
                     significantly superior to marketed corticosteroid including
                     budesonide, fluticasone and ciclesonide
                                                              h pt nx
                                                               e u
                                                                a  c e
                                                              Tr ei i d
                                       D y s
                                       E0 h u
                              D nda
                               5L g e
                              E0 u e m                         D y s
                                                               E0 h u
                   o N
                    m .
                   C po                 nl i
                                         o o
                                       iv t n
                                 / i.
                               m ,. )
                               ( ggt
                                  k                               u
                                                                 o o
                                                               nl i /
                                                               iv t n
                                       m ,.
                                         / i)
                                       ( ggt
                                                              D nda
                                                               5L g e
                                                              E0 u e m
                   U 4
                    N 6
                   S -01           .2
                                   02             5
                                                   0               3.
                   il o
                    c n
                    e d
                   C s ie          0
                                    3             .3
                                                  31               .3
                   us i e
                   Ben d           01
                                   1              .8
                                                  06               .3
                   lt s e
                   u o
                   F ian
                   rp a
                    o t
                   p in            06
                                   0              .6
                                                  03               .9

* Data on file

Investor Presentation / 10

                 Metabolic side effect profile superior to marketed
                  corticosteroid *
                    In liver glycogen deposition screen, deposition of glycogen in
                     liver significantly lower compared to fluticasone and

                                         l c ec t t
                                          y g oe
                                        G o n nn
                             o N
                              m .
                             C po       ( g 0 lv ) t % i ii nf h u
                                           / g r
                                        m 0 ie a     Ih t o y s
                                                      nbo t m
                                           m , t
                                             / i
                                          3g g..
                        US 6
                         N 4
                       S -0 1               1 .2
                                             0            3 1
                                                          -. 6
                        il s i
                        c od
                       Ce ne                2 .6
                                             3             14
                    l i s er i a
                     u o
                      c      oo t
                    Ft a np pne             1 45
                                             16            07
                        us i
                         d od
                       B e ne               5 .7
                                             2             52

       Current global market data : USD 8 billion
       Estimated IND filing : 2008
* Data on file

Investor Presentation / 11

         Prodrug of Gabapentin
         Route of administration : Oral
         Broad therapeutic area : Anti-convulsant / Neuropathy
         Indications : Seizure / CNS related disorders
         Development rationale
            SUN-44 developed to offer higher bioavailability, enhanced
             absorption and reduced dosing frequency
      Current status
            Studies ongoing
                   Acute toxicity

Investor Presentation / 12
       Summary findings from animal studies completed *
                  On equivalent dosage, drug concentration 2-3 times higher
                   compared to existing product in the market
                  rl e lm
                  u ln
                   g s a
                  D vi p a
                      f uU) d
                    M d(N oa X 1pde dgo
                    odg 4 s n P 2o d a r e u
                     d r S 4 e d 1 r r o nupe
                       es    d     3 ee s
                                   5   t   dd xr s
                     r x re n m
                     upe l
                      go l e l
                          s s a
                     de u vi p a
                               s       ei lm
                                         s as
                                       l e pa
    o / .
    s k o r Cno
     e g
     m ,
    D g p D o t i , Ea D
          u nr n ql to
           gc a
              et    u ns
                     i e e
                     v       Du
                              rg  Ea D
                                  ql to D o t i
                                  u ns
                                   i e e r Cno
                                   v        gc a
                                           u nr n
          U cr
           C g
          Atm L ~ g
           ()  h
                m     gp
                     m./ o Cno
                        k,   et
                            nr n
                            o ti   gp
                                    / o
                                     g     A m L
                                            ( ./
                                           C g
                                           U) cr
                                            0-  hm
                            m L m
     5g       5
              8      5g
                      0 m     9
     1g       9
              9       0
                     1g0m    187    0
                                     0      1 9
                                             0 .
     2m      60
              3      0g
                     2m0     15
                              82   2m
                                    00      2 3
                                             3 5
                                            2±0 7

                  LD50 2.5 times higher than competing product under development
                   in Phase III (XP13512 #)‫‏‬
          D rg
           0 u
          L D                                    0m
                                                  0 / k
                                                 2 0 gg
          D N a )
           0S 4   N
          L (U 4s a                              1 0 ggs oh m i drg
                                                 0 m Asf e o ed
                                                  0 / k i t  dif  u
          D 1 1 s , P sI )
           0 X3 2 N  i a I
          L (P 5 a anhe I                        5 mgs oh m i drg
                                                 0 g Asf e o ed
                                                  0 /k i t  di
                                                             f    u
          D U 4s )
           5( N   N
          L 0 S 4a a                             1 0 ggs oh m i drg
                                                 2 m Asf e o ed
                                                  5 / k i t  dif  u
          D P 5 a , P sI )
           5( 1 1  Ni  a I
          L 0 X3 2s anhe I                       > 0 ggs oh m i drg
                                                  5 m Asf e o ed
                                                  0 / k i t   dif  u

                  Found to be safer than XP13512 in animal studies
* Data on file

Investor Presentation / 13                       # XP13512 is a gabapentin prodrug from Xenoport Inc, currently in Phase III

      Clinical advantages
            Possible to achieve higher blood level
            Once-a-day dosing
      Current global market size : USD 1.2 billion (gabapentin is
       a generic product across most markets)‫‏‬
      Estimated IND filing : 2008
      Phase I human studies exposure likely to begin in 2008

Investor Presentation / 14

         Pro-drug of a marketed drug
         Route of administration : Oral / Injectable
         Broad therapeutic area : Skeletal muscle relaxants
         Indications : Muscle spasticity
         Development rationale
            SUN-09 offers quick and improved absorption during entire
             gastro-intestinal tract
      Current status
            Studies ongoing
                   Acute toxicity

Investor Presentation / 15
      Summary findings from animal studies completed *
                       rg e na a
                       D lv i p m
                           s ls
                             M i d u S 0 dea dg
                              o e rg U 9 od d u
                              d d ( N) s n r
                                 x se e na a
                                  pu el s ls
                                 eor l v i p m
            s  ma
               Cx     Drg
                       u     q ln
                            Ei a t C x
                                    ma       Du
         g p
          k o cm
         m , . m L Cc t t n
                /   nn oa
                   oer i ,   Dos
                               e m L Cc t t n
                                    g/      nn o
                                           oer i ,
                   U t ch
                   C) g /
                  A (- m r L m g
                    0    . m ck/
                              g,           C) g /
                                         U t ch . m
                                        A (- m r L
          20   36
                .      1
                       5      20    8         4

               At equivalent dosage, AUC 1.6 times higher than existing
                marketed products
      Substantially improved efficacy seen in muscle coordination in
            animal model
      Current global market size : USD 200 million (all existing
            products are generic)‫‏‬
      No. of spastic patients under treatment (US+Europe) : 1.5
      Likely IND filing : 2008
* Data on file

Investor Presentation / 16
                                NDDS Technology Platforms

      Dry powder inhalers
      Controlled release systems
            Gastric retention systems (GRID)‫‏‬
            Matrix system (Wrap-matrix)‫‏‬
      Targeted drug delivery
      Biodegradable injections/implants

Investor Presentation / 17

      Inhalers used for Asthma and COPD
      Device can be modified for systemic delivery of drugs to
      Easy to use
            Simple operating sequence of 3 steps : Open-inhale-close
      Small and convenient to carry
      Multiple dose device
      Being developed to comply with US FDA and European
       requirements for inhalation device

Investor Presentation / 18

      Device engineered to
            Give visual, audible and tactile feedback
            Deliver uniform dose over a range of patient effort (flow
             rates/patient inhalation effort)‫‏‬
            Eliminate double dosing and dose wastages
            Deliver multiple doses in one device with fail-safe dose
            Deliver consistently higher drug to lungs
            Easy use by children, adults and elderly
      Can be used in delivery of
            Existing combinations of steroid and bronchodilators
            NCE steroid

Investor Presentation / 19
                                                 DPI based product

      Developing a combination of steroid and bronchodilator
       with improved formulation
      Current status
            Semi-regulated markets
                   Expected launch : 2009
            Regulated markets
                   Expected NDA filing : 2011

Investor Presentation / 20
                             Gastro Retentive Innovative Device (GRID)‫‏‬

      Development Rationale
            Some drugs have narrow zones of absorption in GI tract
                   Poor solubility and degradation in alkaline media of small
                   Carrier mediated transport mechanism
                   Relatively short residence time in stomach and small intestine
                   Decreased absorption hence unsuitable for once a day
      Gastro Retentive systems
            Designed for retention in the stomach for longer time than
             usual (~about 8 hours)‫‏‬
            Mechanisms involved
                   Size expansion

Investor Presentation / 21

      Key features of GRID
            Coated multilayered dosage form
            Floats instantaneously
            Swells upto 8 times its initial volume
            Maintains physical integrity
            Flexible and soft
      Clinical advantages
            Once-a-day dosing improves patient compliance
            Reduced side effects
            Different types of release profiles possible (IR + SR)‫‏‬

Investor Presentation / 22
                                                Baclofen GRS Capsule

      Once-a-day dosing against 3 to 4 times of marketed
      Indications : Muscle spasticity
      Current status
                   Completed Phase I, II & III clinical studies
            Completed pre-IND meeting with US FDA
                   IND filing : 2008

Investor Presentation / 23
                                         Baclofen GRS Capsule

      Clinical outcome
            Once-a-day rated better by patients than three-times-a-day
            Ease of switchover from IR (3 times / day) to GRS (once-a-
            As effective (non-statistically superior)‫‏‬
            Reduced sedation (statistically superior)‫‏‬
            No unanticipated significant adverse event

Investor Presentation / 24
                                                                   Wrap Matrix System

      Key features
            Controlled release of drug for once-a-day administration
            Controlled release of drug for high dose – high solubility
            pH independent performance
            Capable of different types of release profiles (IR + SR)‫‏‬
                                   Disease Specific Drug Release Patterns

             IR + SR (useful in pain           IR + SR + IR (for         SR + IR (for eg in
             management)                                                 Heart diseases)‫‏‬
                                               eg in asthma)

            High drug to excipient ratio

Investor Presentation / 25
                                           Wrap Matrix System

      Clinical advantage
            Once-a-day dosing
            Reduces the side effects, leading to patient compliance
            Relatively smaller size of dosage form
            No residual drug in dosage form on evacuation
            Minimal effect of food
            Reproducing similar bio-equivalence difficult for products
             based on other competing technology
                   Low risk of generics
      Detailed presentation made to US FDA

Investor Presentation / 26
                             Wrap Matrix System based products

      Proven technology : Commercially validated and scaled-up
      Metoprolol XL
            Once-a-day dosing against 2 to 3 times of marketed product
            Indications : Hypertension / Angina
            Current status
                   India : Approved
      Based on this technology, a few ANDAs for controlled
       release dosage form filed with US FDA

Investor Presentation / 27

      Key features of technology for cytotoxic substances
            Avoids toxic excipients
            Better safety index as proven in animal model
            Increases circulation half life and improved efficacy
            More drugs can be delivered at target site
            Avoids hypersensitivity reaction to toxic excipients
            Uses all approved excipients in injectable products
      Nanoparticle platform technology at preclinical
       development stage with demonstrated proof of concept
      Based on this technology, 2 cytotoxic products are being

Investor Presentation / 28
                             Biodegradable implants / injections

      Key Features of technology developed
            Can produce controlled particle size for facile injection
             through conventional needle to reduce patient trauma and
            No local anaesthetic required while delivering the drug
            Closed semi-automatic process to give kilogram scale,
             reproducible, consistent and uniform microsphere product
            Technology can be applied to peptides
            Quantity of the drug product required to be injected is less
             to get similar profile.
            No toxic solvents used in the formulation
            Easy for reconstitution and mixing

Investor Presentation / 29
                             Biodegradable implants / injections

      GnRH analogue
            Comparable to marketed products
                   Achieved comparable profile in animals
                   Injection less painful
                   Easy to use
                   No need of local anaesthesia
            Current status
                   Preclinical studies ongoing
                   Clinical studies planned in India : 2008
      Somatostatin analogue
            Comparable to marketed products
                   Achieved comparable profile in animals
                   Easy to use
            Current status
                   Clinical studies in India ongoing
Investor Presentation / 30
                                       NCE Next Milestones

         SUN-1334H : IND filed in 2006, Phase III in 2008
         SUN-461 : IND filing 2008
         SUN-44 (Prodrug of Gabapentin): IND filing 2008
         SUN-09 (Prodrug of a marketed drug) : IND filing 2008

Investor Presentation / 31
                                         NDDS Next Milestones
      DPI
             Semi-regulated markets
                    Expected launch : 2009
             Regulated markets
                    Expected NDA filing : 2011
      Baclofen GRS
             Approved in India
             IND filing 2008
     Biodegradable Implements / Injections
             GnRH Analogue (For India) : Phase I in 2008
             Somatostatin Analogue (For India) : Phase I ongoing

Investor Presentation / 32
                                                         Financial Summary
                                                                       (in Rs '000)
                             P&L Summary    Q1 FY09       Q1 FY08         FY 08

                      Total Income             47,300          120         375,278

                      Total Expenditure       103,000       96,654         408,218

                      Net Profit / (Loss)     (58,100)      (99,564)       (48,827)

     Fully diluted no of equity shares : 207 million
     Market capitalisation : MINR 19,500 (MUSD 450)

Investor Presentation / 33
Thank you

Shared By: