The development of RNA- modulating therapies: Prosensa’s DMD programme Aktion Benni Mitgliederversammlung 3 May 2014; Hamburg Claire Leyten Manager Patient Group Relations - Prosensa
Forward-looking statements This presentation may contain statements that constitute “forward -looking statements” within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. Forward-looking statements are statements other than historical fact and may include statements that address future operating, financial or business performance or Prosensa’s strategies or expectations. In some cases, you can identify these statements by forward-looking words such as “may,” “might,” “will,” “should,” “expects,” “plans,” “anticipates,” “believes,” “estimates,” “predicts,” “projects,” “potential,” “outlook” or “continue,” and other comparable terminology. Forward-looking statements are based on management’s current expectations and beliefs and involve significant risks and uncertainties that could cause actual results, developments and business decisions to differ materially from those contemplated by these statements. These risks and uncertainties include, but are not limited to, the timing and conduct of clinical trials of drisapersen and Prosensa’s other product candidates, plans to pursue research and development of product candidates for DMD and other indications, the clinical utility of Prosensa’s product candidates, the timing or likelihood of regulatory filings and approvals, Prosensa’s intellectual property position, expectations regarding payments under Prosensa’s collaborations and Prosensa’s competitive position. These risks and uncertainties also include those described under the captions “Risk Factors” and “Management’s Discussion and Analysis of Financial Condition and Results of Operations” in Prosensa’s Annual Report on Form 20-F and other filings with the Securities and Exchange Commission. Forward-looking statements speak only as of the date they are made, and Prosensa does not undertake any obligation to update them in light of new information, future developments or otherwise, except as may be required under applicable law. All forward-looking statements are qualified in their entirety by this cautionary statement. 1
What will we discuss? Prosensa’s pipeline in Duchenne muscular dystrophy (DMD) Recap of recent events Further analyses of drisapersen data Prosensa’s re -dosing intentions The natural history study R&D programmes for other mutations Q&A 2
Recent & upcoming events Jan 12, 2014: Prosensa regains rights to drisapersen from GSK Jan 16, 2014: Prosensa reports initial findings of further analyses Jan 21, 2014: Prosensa webinar for the patient community Feb 18, 2014: Communication to patient groups announcing next steps towards potential re-dosing Mar 18, 2014: Announcement of intent to re-dose an initial group of boys in Q3 2014 Mar 25, 2014: UPPMD Webinar for the patient community Apr 29, 2014: Communication to patient groups with about re-dosing and regulatory path 3
R&D Pipeline Indication Compound Discovery Pre-Clinical Phase I/II Phase III Drisapersen 13% of DMD patients 6% of DMD patients PRO044 PRO045 8% of DMD patients Duchenne 8% of DMD patients Muscular PRO053 Dystrophy 4% of DMD patients PRO052 PRO055 2% of DMD patients PROSPECT Myotonic PRO135 Dystrophy Huntington’s PRO289 Disease 4
Drisapersen Clinical Program More than 300 patients and over 450 patient treatment years in global clinical program Study Phase Study design n Status CLIN-02 Open label, repeat dose escalation (extension Complete; Phase I/II 12 DMD114673 phase 6 mg/kg/wk intermittent extension ongoing Placebo-controlled, pharmacokinetics/safety; DEMAND I Phase I 20 Complete DMD114118 single dose Exploratory placebo-controlled, DEMAND II Phase II 53 Complete dose regimen comparison; ex-US DMD114117 Randomized, placebo-controlled, confirmatory DEMAND III Phase III 186 Complete study DMD114044 Ph II/III Open label, extension study for DEMAND II & DEMAND IV 234 Closed Extension DEMAND III; 2 years DMD114349 Exploratory placebo-controlled, DEMAND V Phase II 51 Complete dose-comparison; US only DMD114876 5
Drisapersen DMD114673 Efficacy results appear to show delay of disease progression 800 Age at week 177 700 13.7 Distance walked (m) 14.3 600 11.4 500 12.6 400 10.9 9.3 300 13.3 200 15.4 8 weeks on – 4 weeks off 100 13.0 14.8 0 0 12 24 36 48 60 72 80 93 105 117 129 141 153 165 177 Weeks
Drisapersen DMD114673 Efficacy results appear to show delay of disease progression 800 Age at week 177 700 Distance walked (m) 600 500 400 Mean age 12.9 300 Mean change from baseline: -24.5 m 200 Median change from baseline: +7.5 m 100 0 0 12 24 36 48 60 72 80 93 105 117 129 141 153 165 177 Weeks
6MWT Efficacy Results: DEMAND II, V Two placebo-controlled studies show treatment benefit on 6MWT Placebo Drisapersen 6 mg/kg/week Δ 6MWD = +35m p=0.014 Δ 6MWD = +31m Δ 6MWD = +27m p=0.003 p=0.069 +32m (n=18) +20m (n=36) 20 +16m (n=18) -4m (n=18) -11m (n=16) -11m (n=34) (11) DEMAND II DEMAND V DEMAND II + DEMAND V (25 week endpoint) (24 week endpoint) (post-hoc analysis 24/25 weeks) 8
Summary of 6MWT Efficacy Data Two out of three placebo-controlled studies show clinically meaningful improvement in 6MWT (primary endpoint) for drisapersen with respect to placebo Trial duration Clinically Statistically Study Phase; study design n (weeks) meaningful significant ✓ ✓ DEMAND II Exploratory (Phase II); placebo-controlled, 53 48 dose regimen comparison, patients in early DMD114117 (35 m) (p=0.014) disease stage ✓ ✗ Exploratory (Phase II); placebo-controlled, DEMAND V 51 24 dose comparison, patients in early disease DMD114876 (27 m) (p=0.069) stage ✗ ✗ Confirmatory (Phase III); placebo- DEMAND III 186 48 controlled, patients in early and later DMD114044 (10 m) (p=0.415) disease stage 9
DEMAND III included older patients… Age (yrs), mean (sd), range Study Treatment 6.9 (1.2) Placebo 5-9 DEMAND II DMD114117 7.2 (1.7) Drisapersen 5-11 8.0 (1.8) Placebo 5-11 DEMAND V DMD114876 7.6 (2.7) Drisapersen 5-13 8.0 (2.4) Placebo 5-16 DEMAND III DMD114044 8.3 (2.4) Drisapersen 5-16 10 Drisapersen arm = 6 mg/kg/week
…with more advanced disease… Baseline characteristics for Drisapersen 6 mg/kg/week groups The drisapersen arm boys in DEMAND III were generally more advanced in their disease DEMAND II DEMAND V DEMAND III +29% +167% +48% -21% -18% 58 12.3 4.7 428 129 124 396 5.0 47 4.6 3.3 45 3.1 337 102 Time since Rise from 4 stairs climb- 6MWD Muscle diagnosis floor time ascent time [meter] strength [lbs] [months] [sec] [sec] 11
…in both treatment arms Baseline characteristics for placebo groups The placebo arm boys in DEMAND III were generally more advanced in their disease DEMAND II DEMAND V DEMAND III +22% +187% +30% -14% -19% 54 13.4 4.6 416 128 403 122 46 4.7 4.5 3.5 44 3.5 348 99 Time since Rise from 4 stairs climb- 6MWD Muscle diagnosis floor time ascent time [meter] strength [lbs] [months] [sec] [sec] 12
DEMAND III was Part of a Global Program More than 50 trial sites in 25 countries on 5 continents
Overview of supportive studies + analyses n Treatment Study Design Week P-value pb/dr* difference DEMAND II db pb controlled 16/16 25 +35m 0.014 DEMAND V db pb controlled 16/18 24 +27m 0.069 DEMAND II+V integrated analysis 34/36 24 +31m 0.003 DEMAND III db pb controlled 59/117 48 +10m 0.415 DEMAND III, ≤7 pre-specified analysis 29/51 48 +21m 0.131 DEMAND III+II, ≤7 integrated analysis 42/62 48 +24m 0.048 DEMAND III, >7,300-450 subset analysis 14/34 48 +25m 0.292 DEMAND IV long-term open label 44/69 96 +46m NA DMD114673 long-term open label 12 177 NA NA pb = placebo (DEMAND IV: pb/delayed treatment); dr = drisapersen 6 mg/kg; Tx difference on 6MWD; not all analyses shown
Creatine Kinase Decrease Consistent decrease in Creatine Kinase (CK) across three placebo controlled studies CK levels [IU/L]¹ Drisapersen 6mg ∆ in CK level between Drisapersen DEMAND II Placebo DEMAND V² (6mg/kg/wk) and placebo 14,000 DEMAND III DEMAND II -3,327 12,000 (at week 25) (p=0.064) 10,000 DEMAND V -1,305 (at week 24) (p=0.439) 8,000 DEMAND III -4,045 6,000 (at week 48) (p<0.001) 0 0 10 20 30 40 50 Week ¹Preliminary analysis; ²Treatment duration 24 weeks 15
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