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Sosei Group Corporation: Data at ERS Shows Efficacy of Once-daily COPD Portfolio Versus Comparators, Further Establishes Dual-bronchodilator QVA149

September 2, 2012

TOKYO, September 3, 2012 /PRNewswire/ –

        - QVA149 demonstrated superior bronchodilation compared to indacaterol 150
          mcg, glycopyrronium 50 mcg, salmeterol/fluticasone 50/500 mcg BID, OL tiotropium 18
          mcg and placebo[1,2]
        - Seebri(R) Breezhaler(R) (glycopyrronium bromide) demonstrated rapid, sustained
          bronchodilation and reduced exacerbations similar to OL tiotropium 18 mcg in GLOW
          pooled data analysis[3,4]

Sosei Group Corporation (“Sosei”; TSE Mothers Index: 4565) highlights that further
data from the once-daily chronic obstructive pulmonary disease (COPD) clinical trial
programs were presented today by Novartis at the European Respiratory Society (ERS)
Congress. Overall, Novartis presented 14 abstracts, including data from the
investigational QVA149 (fixed-dose combination of indacaterol maleate / glycopyrronium
bromide) IGNITE Phase III clinical trial program, and the glycopyrronium bromide
(Seebri(R) Breezhaler(R)) GLOW Phase III clinical trial program.

Among the data presented, three new studies from the investigational QVA149 IGNITE
Phase III clinical trial program (SHINE, ILLUMINATE and ENLIGHTEN) demonstrated that
QVA149 significantly improved lung function compared to other COPD therapies[1,2,6].Data
from the GLOW program showed that glycopyrronium 50 mcg once daily provided rapid and
sustained bronchodilation, and reduced exacerbations and symptoms when compared to
placebo, similar to the levels observed with open-label (OL) tiotropium 18 mcg[3,4].

IGNITE data demonstrated the efficacy of the dual-bronchodilator QVA149 (indacaterol
maleate / glycopyrronium bromide) and showed a superior effect on lung function and
patient-reported outcomes versus comparators[1,2,6]

SHINE met its primary endpoint by demonstrating that once-daily QVA149 110/50 mcg
improved lung function as measured by trough FEV1 compared to once-daily indacaterol
maleate 150 mcg (+70mL above indacaterol alone; p<0.001) and once-daily glycopyrronium 50
mcg (+90mL above glycopyrronium alone; p<0.001)[1]. QVA149 110/50 mcg is an
investigational inhaled dry-powder fixed-dose combination medication that provides the
equivalent amount of indacaterol as Onbrez (indacaterol maleate) 150 mcg along with
glycopyrronium 50 mcg[7]. QVA149 was also more effective at improving lung function
compared to OL tiotropium 18 mcg (+80mL above tiotropium; p<0.001) and placebo (+200mL;
p<0.001)[1]. Mean peak FEV1 at Week 26 was also significantly higher with QVA149 compared
to placebo (+330mL, p<0.001), indacaterol 150 mcg (+120mL; p<0.001), glycopyrronium 50 mcg
(+130mL; p<0.001) and OL tiotropium 18 mcg (+130mL; p<0.001)[1]. Mean FEV1 area under the
curve (AUC) for 0-24hr at Week 26 was significantly higher with QVA149 compared to placebo
(+320mL, p<0.001), indacaterol 150 mcg (+110mL; p<0.001), glycopyrronium 50 mcg (+110mL;
p<0.001) and OL tiotropium 18 mcg (+110mL; p<0.001)[1].

The results also showed that QVA149 improved breathlessness measured by the transition
dyspnea index or TDI (p<0.001 versus placebo; p<0.05 versus OL tiotropium 18 mcg),
increased health-related quality of life (HRQoL) measured by the St George’s Respiratory
Questionnaire or SGRQ (p<0.01 versus placebo; p<0.05 versus OL tiotropium 18 mcg) and
reduced rescue medication use (p<0.001 versus both placebo and OL tiotropium 18 mcg)[1].
QVA149 was superior to indacaterol 150 mcg and glycopyrronium 50 mcg at reducing use of
rescue medication (p<0.05 and p<0.001 respectively) and also provided numerically higher
improvements in breathlessness and HRQoL compared to indacaterol 150 mcg and
glycopyrronium 50 mcg[1].

ILLUMINATE compared QVA149 110/50 mcg to the twice-daily LABA/ICS
salmeterol/fluticasone 50/500 mcg head-to-head over 26 weeks in patients with COPD [2].
The study met its primary endpoint by demonstrating that the mean FEV1 area under the
curve (AUC) for 0-12hr at Week 26 was significantly higher with QVA149 compared to
salmeterol/fluticasone 50/500 mcg (+140mL; p<0.001)[2]. Mean FEV1 AUC0-12h was also
significantly higher with QVA149 versus salmeterol/fluticasone 50/500 mcg at Day 1 (+70mL;
p<0.001)[2]and Week 12 (+120mL; p<0.001)[2]. The ILLUMINATE trial also demonstrated that
QVA149, in comparison to salmeterol/fluticasone 50/500 mcg, significantly improved
breathlessness measured by TDI (p=0.003) and reduced rescue medication use (p=0.019) over
26 weeks[2].

ENLIGHTEN demonstrated the efficacy of QVA149 at improving lung function over a
52-week period by showing that QVA149 increased FEV1 and forced vital capacity (FVC)
versus placebo at Day 1 and Weeks 3, 6, 12, 26, 39 and 52 (p<0.001)[6]. At Week 52, the
mean difference in FEV1 compared to placebo at 60 minutes post-dose was +257mL
(p<0.001)[6].

QVA149 was generally well tolerated in the SHINE, ILLUMINATE and ENLIGHTEN trials with
an incidence of adverse events that was similar between respective groups[1,2,6].

GLOW pooled analyses demonstrated that investigational glycopyrronium increased lung
function, improved patient outcomes compared to placebo[3,4]

Results of the first pooled analysis of GLOW1 and GLOW2 data demonstrated that
patients on glycopyrronium 50 mcg experienced rapid, sustained and clinically meaningful
bronchodilation over 52 weeks[3]. The improvement in FEV1 was seen within five minutes
after the first dose on Day 1 (+90mL at 5 minutes and +144mL at 15 minutes versus placebo;
p<0.001) and was sustained throughout the 52-week period (p<0.001 vs. placebo)[3]. FEV1
AUC for 0-4h, 0-12h, 0-24h and 12-24h for glycopyrronium 50 mcg was statistically
significantly greater than placebo (p<0.05) and numerically greater than OL tiotropium 18
mcg (an exploratory arm in GLOW2) when compared to placebo on Day 1 and Weeks 12, 26 and
52[3]. When compared to placebo, glycopyrronium 50 mcg was also numerically higher than OL
tiotropium 18 mcg versus placebo at all-time points for trough FEV1 (Day 1 and Weeks 12,
26 and 52)[3].

The second pooled analysis of GLOW1 and GLOW2 data found that for patients taking
glycopyrronium 50 mcg, the time to first moderate/severe exacerbation was significantly
prolonged compared to placebo at both Week 26 (hazard ratio [HR] 0.64; p<0.001) and Week
52 (HR 0.67; p<0.001)[4]. The results were comparable in patients treated with OL
tiotropium 18 mcg. Glycopyrronium 50 mcg also significantly lowered the rate of
moderate/severe exacerbations versus placebo at Weeks 26 and 52 (both rate ratio [RR]
0.66; p<0.005)[4].

Glycopyrronium 50 mcg improved breathlessness measured by TDI (p<0.05) and
health-related quality of life measured by SGRQ (p<0.001) at Weeks 26 and 52[4]. The
results were similar to OL tiotropium 18 mcg compared to placebo[4].

About the study designs

SHINE was a 26 week, multicenter, randomized, double-blind, parallel-group, placebo
and active controlled pivotal trial of 2,144 patients with moderate-to-severe COPD to
assess efficacy in terms of trough FEV1[1]. Patients were randomized to receive QVA149,
indacaterol maleate 150 mcg, glycopyrronium 50 mcg, OL tiotropium 18 mcg or placebo.

ILLUMINATE was a 26 week, multi-center, randomized, double-blind, double dummy,
parallel-group study to assess the efficacy, safety and tolerability of once-daily QVA149
compared to twice-daily fixed dose combination of salmeterol/fluticasone 50/500 mcg in
patients with moderate-to-severe stable COPD[2].

ENLIGHTEN was a 52 week, multicenter, randomized, double-blind, parallel-group,
placebo controlled pivotal trial of 339 patients with moderate-to-severe COPD to assess
the safety and tolerability of QVA149[6].

GLOW1 and GLOW2 were multicenter, randomized, double-blind, placebo controlled,
parallel group studies in patients with moderate-to-severe COPD. GLOW1 was a 26 week study
with patients randomized to receive once-daily glycopyrronium 50 mcg or placebo. GLOW2 was
a 52 week study with patients randomized to receive once-daily glycopyrronium 50 mcg or
placebo, and included an exploratory arm to compare the effects of once-daily OL
tiotropium 18 mcg versus placebo[3,4].

The first pooled analysis assessed the efficacy of once-daily glycopyrronium 50 mcg
versus placebo and once-daily OL tiotropium 18 mcg over 26 to 52 weeks in 1,888 patients
with moderate-to-severe COPD from clinical trials (GLOW1 and GLOW2)[3]. The second pooled
analysis assessed the efficacy of once-daily glycopyrronium 50 mcg versus placebo and
once-daily OL tiotropium 18 mcg at reducing COPD exacerbations, symptoms and improving
health status over 26 to 52 weeks in 1,854 patients from clinical trials (GLOW1 and
GLOW2)[4].

CEO of Sosei, Shinichi Tamura commented:

“We are very encouraged by the substantial body of GLOW and IGNITE data presented at
the European Respiratory Society meeting and look forward to the approval
of glycopyrronium bromide in Europe and the filing of QVA149 in Europe and Japan.”

Notes for editors

About NVA237/QVA149

NVA237 (glycopyrronium bromide – Seebri(R) Breezhaler(R)) was licensed to Novartis in
April 2005 by Sosei and its co-development partner, Vectura. Glycopyrronium bromide is an
investigational LAMA developed as a once-daily inhaled maintenance therapy for the
treatment of COPD. Phase III data from the GLOW 1, 2 and 3 studies demonstrated that
glycopyrronium increased patients’ lung function over a 24-hour period compared to placebo
with a fast onset of action at first dose, and improved exercise endurance versus
placebo[12-14]. In June 2012, the European Medicines Agency’s Committee for Medicinal
Products for Human Use (CHMP) adopted a positive opinion for the approval of
glycopyrronium bromide in Europe under the brand name Seebri(R) Breezhaler(R).

QVA149 is an investigational inhaled, once-daily, fixed-dose combination of
indacaterol maleate and glycopyrronium bromide. QVA149 is being investigated for the
treatment of COPD in the Phase III IGNITE clinical trial program. IGNITE is one of the
largest international clinical trial programs in COPD comprising 10 studies in total with
more than 7,000 patients across 42 countries[1,2,6,15-21]. The first five studies
(ILLUMINATE, SHINE, BRIGHT, ENLIGHTEN, SPARK) have already completed in 2012 with three
additional studies (BLAZE, ARISE, BEACON) expected to complete by the end of the year. The
studies are designed to investigate efficacy, safety and tolerability, lung function,
exercise endurance, exacerbations, breathlessness and quality of life. Initial filings for
regulatory approval are expected in Q4 2012 for Europe and Japan. US filing is expected at
the end of 2014.

All Novartis COPD portfolio products are being developed for delivery via the
Breezhaler(R) device, a single-dose dry powder inhaler (SDDPI), which has low air flow
resistance, making it suitable for patients with airflow limitation, such as COPD
patients. The Breezhaler(R) device allows patients to hear, feel and see that they have
taken the drug correctly[19].

About COPD

COPD is a progressive disease associated mainly with tobacco smoking, air pollution or
occupational exposure, which can cause obstruction of airflow in the lungs resulting in
debilitating bouts of breathlessness. It affects an estimated 210 million people
worldwide[22] and is predicted to be the third leading cause of death by 2020[23].
Although COPD is often thought of as a disease of the elderly, 50% of patients are
estimated to be within the ages of 50 and 65, which means that half of the COPD population
are likely to be impacted at the peak of their earning power and family responsibilities[
24].

About Sosei

Sosei is an international biopharmaceutical company anchored in Japan with a global
reach. It practises a reduced risk business model by acquiring compounds from, and
bringing compounds into, Japan through exploitation of its unique position within global
markets.

For further information about Sosei, please visit http://www.sosei.com.

Forward-looking statements

This press release contains forward-looking statements, including statements about the
discovery, development and commercialisation of products. Various risks may cause Sosei’s
actual results to differ materially from those expressed or implied by the forward-looking
statements, including: adverse results in clinical development programmes; failure to
obtain patent protection for inventions; commercial limitations imposed by patents owned
or controlled by third parties; dependence upon strategic alliance partners to develop and
commercialise products and services; difficulties or delays in obtaining regulatory
approvals to market products and services resulting from development efforts; the
requirement for substantial funding to conduct research and development and to expand
commercialisation activities; and product initiatives by competitors. As a result of these
factors, prospective investors are cautioned not to rely on any forward-looking
statements. We disclaim any intention or obligation to update or revise any
forward-looking statements, whether as a result of new information, future events or
otherwise.

References

        1) Bateman E et al. Benefits of dual bronchodilation with QVA149 once daily
          versus placebo, indacaterol, NVA237 and tiotropium in patients with COPD: the SHINE
          study. [ERS abstract 700179; Session 306; Monday September 3, 2012; 14:45:-16:45].
        2) Vogelmeier C et al. Once-daily QVA149 significantly improves lung function
          and symptoms compared to twice-daily fluticasone/salmeterol in COPD patients: The
          ILLUMINATE study. [ERS abstract 70045; Session 52; Sunday September 2, 2012;
          08:30-10:30].
        3) Banerji D et al. Once-daily NVA237 improves lung function in COPD patients:
          pooled results of the GLOW1 and GLOW2 studies. [ERS abstract 853239; Session 245;
          Date: September 03, 2012 Time: 12:50-14:40.
        4) Banerji D et al. Once-daily NVA237 reduces exacerbations and improves
          symptoms in COPD patients: a pooled analysis, of the GLOW1 and GLOW2 studies. [ERS
          abstract 853213; Session 314; Date: September 03, 2012 Time: 14:45-16:45.
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http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/001114/human_med_001219.jsp&mid=WC0b01ac058001d124

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SOURCE Sosei Group Corporation


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