* If approved, PiaSky will be the first monthly subcutaneous (SC) treatment

    for paroxysmal nocturnal haemoglobinuria (PNH) in the EU
  * Additionally, with the option to self-administer, PiaSky may provide an
    alternative to existing intravenous (IV) C5 inhibitors, potentially helping
    to reduce treatment burden(1)
  * The recommendation is based on the COMMODORE 2 study results, where SC
    PiaSky given every month demonstrated equivalent disease control and
    comparable safety to IV eculizumab given every two weeks(2,3)

Basel, 28 June 2024 - Roche (SIX: RO, ROG; OTCQX: RHHBY) announced today that
the European Medicines Agency's (EMA) Committee for Medicinal Products for Human
Use (CHMP) has adopted a positive opinion for PiaSky® (crovalimab) for the
treatment of paroxysmal nocturnal haemoglobinuria (PNH). The CHMP has
recommended PiaSky, a novel recycling monoclonal antibody that inhibits the
complement protein C5, for use in adults and adolescents (12 years of age or
older with a weight of 40 kg) who are either new to, or have been previously
treated with C5 inhibitors. If approved, PiaSky will be the first monthly
subcutaneous (SC) treatment for PNH in the European Union, with the option to
self-administer following adequate training. This may provide an alternative
option to current C5 inhibitors that require regular intravenous (IV) infusions,
potentially helping to reduce treatment burden and disruption to the lives of
people with PNH and their caregivers.(1 )A final decision regarding the approval
of PiaSky is expected from the European Commission in the near future.
"People living with PNH face lifelong treatment, often requiring frequent
intravenous infusions and time-consuming clinic visits," said Levi Garraway,
M.D., Ph.D., Roche's Chief Medical Officer and Head of Global Product
Development. "With the option to self-administer once a month, today's
recommendation may therefore offer patients and caregivers in Europe more
freedom in their day-to-day lives."
PNH is a rare and life-threatening blood condition, which affects approximately
20,000 people worldwide. In PNH, red blood cells are destroyed by the complement
system - part of the innate immune system. This causes symptoms such as anaemia,
fatigue and blood clots, and can lead to kidney disease. C5 inhibitors -
treatments that block part of the complement system cascade - have been shown to
be effective in treating PNH. PiaSky is a novel C5 inhibitor that is recycled
within the bloodstream, allowing the medicine to bind and inhibit the C5 protein
multiple times and to act longer in the body with a small volume of medicine.
This enables SC administration every four weeks, following an initial IV
infusion and weekly SC loading doses in the first month of treatment.(1,2,4-6)
The CHMP recommendation is based on the results from the Phase III COMMODORE 2
study in people with PNH who have not been previously treated with C5
inhibitors. Results from the study demonstrated that PiaSky, administered as SC
injections every four weeks, achieved disease control and was well-tolerated.
PiaSky was non-inferior with comparable safety to eculizumab, an existing
standard of care C5 inhibitor, given intravenously every two weeks. The rate of
adverse events in people treated with PiaSky was similar to treatment with
eculizumab (78% versus 80%, respectively). The application included supportive
data from two additional Phase III studies, the COMMODORE 1 study, in people
with PNH switching from currently approved C5 inhibitors, and the COMMODORE 3
study in people new to C5 inhibitor treatment in China.(2,7,8,9 )
PiaSky is the first monthly SC treatment approved in the US, Japan and China for
people with PNH based on results of the COMMODORE studies.(2,7,9)
PiaSky is being investigated in a broad clinical development programme,
including five ongoing Phase III studies and three earlier phase studies in
complement-mediated diseases, including PNH, atypical haemolytic uremic syndrome
and sickle cell disease.(2,7,9-14)
About PiaSky® (crovalimab)
PiaSky® (crovalimab) is a novel recycling monoclonal antibody that inhibits the
complement protein C5 and is designed to block the complement system - a vital
part of the innate immune system that acts as the body's first line of defence
against infection. PiaSky has been engineered by Chugai Pharmaceutical Co. Ltd
to address certain needs of people living with complement-mediated diseases,
including providing patients with a potential for self-administration following
adequate training.
PiaSky works by binding to C5, blocking the last step of the complement cascade
and delivering rapid and sustained complement inhibition. It is also recycled
within the bloodstream, enabling small volume subcutaneous administration every
four weeks. In addition, PiaSky binds to a different C5 binding site from
current treatments, which has the potential to provide a treatment option for
people with specific C5 gene mutations who do not respond to current therapies.
PiaSky is a monthly subcutaneous treatment approved in the US, Japan and China
for people with paroxysmal nocturnal haemoglobinuria, based on the Phase III
COMMODORE studies. It is also being evaluated in atypical haemolytic uremic
syndrome and sickle cell disease.(1,2,7,9-1)(4)
About the COMMODORE 2 study
The COMMODORE 2 study is a Phase III, randomised, open-label study evaluating
the efficacy and safety of PiaSky® (crovalimab) versus eculizumab in people with
paroxysmal nocturnal haemoglobinuria (PNH) who have not been treated previously
with C5 inhibitors. The study's co-primary efficacy endpoints measure
transfusion avoidance and control of haemolysis (the ongoing destruction of red
blood cells measured by lactate dehydrogenase levels). The adults enrolled in
the study were randomised in a 2:1 ratio to be treated with either subcutaneous
(SC) PiaSky every four weeks or intravenous eculizumab every two weeks. The
participants who were less than 18 years old were included in a non-randomised
treatment arm and were treated with SC PiaSky every four weeks.(3)
About Roche
Founded in 1896 in Basel, Switzerland, as one of the first industrial
manufacturers of branded medicines, Roche has grown into the world's largest
biotechnology company and the global leader in in-vitro diagnostics. The company
pursues scientific excellence to discover and develop medicines and diagnostics
for improving and saving the lives of people around the world. We are a pioneer
in personalised healthcare and want to further transform how healthcare is
delivered to have an even greater impact. To provide the best care for each
person we partner with many stakeholders and combine our strengths in
Diagnostics and Pharma with data insights from the clinical practice.
In recognising our endeavour to pursue a long-term perspective in all we do,
Roche has been named one of the most sustainable companies in the
pharmaceuticals industry by the Dow Jones Sustainability Indices for the
fifteenth consecutive year. This distinction also reflects our efforts to
improve access to healthcare together with local partners in every country we
work.
Genentech, in the United States, is a wholly owned member of the Roche Group.
Roche is the majority shareholder in Chugai Pharmaceutical, Japan.
For more information, please visit www.roche.com (http://www.roche.com).
All trademarks used or mentioned in this release are protected by law.
References
(1)Fukuzawa T, et al. Long lasting neutralisation of C5 by SKY59, a novel
recycling antibody, is a potential therapy for complement-mediated diseases.
2017; Sci Rep 7, 1080.
(2)Roth A, et al. The Phase III, Randomised COMMODORE 2 Trial: Results from a
Multicentre Study of Crovalimab vs Eculizumab in Paroxysmal Nocturnal
Hemoglobinuria (PNH) Patients Naïve to Complement Inhibitors. Presentation at
European Hematology Association (EHA) Annual Congress; 2023 June 08-13. Abstract
#S181.
(3 )COMMODORE 2 (NCT04434092). (Internet; cited June 2024) Available at:
https://www.clinicaltrials.gov/ct2/show/NCT04434092.
(4)Grand View Research. Paroxysmal nocturnal hemoglobinuria (PNH) treatment
market size, share and trends analysis report by treatment and segment
forecasts, 2018 - 2025. (Internet; cited June 2024). Available at:
https://www.grandviewresearch.com/industry-analysis/paroxysmal-nocturnal-
hemoglobinuria-pnh-market.
(5) National Organization for Rare Diseases. Paroxysmal nocturnal
hemoglobinuria. (Internet; cited June 2024). Available at:
https://rarediseases.org/rare-diseases/paroxysmal-nocturnal-hemoglobinuria/.
(6)Harder M, et al. Incomplete inhibition by eculizumab: mechanistic evidence
for residual C5 activity during strong complement activation. Blood.
2017;129:970-980.
(7)Scheinberg P, et al. Phase III Randomised, Multicentre, Open-Label COMMODORE
1 Trial: Comparison of Crovalimab Vs Eculizumab in Complement Inhibitor-
Experienced Patients with Paroxysmal Nocturnal Hemogobinuria (PNH). Presentation
at European Hepatology Association (EHA) Annual Congress; 2023 June 08-13.
Abstract #S183.
(8)COMMODORE 1 (NCT04432584). (Internet; cited June 2024) Available at:
https://www.clinicaltrials.gov/ct2/show/NCT04432584.
(9)Liu H, et al. Six-month Crovalimab Extension in the Phase III COMMODORE 3
Study: Updated Efficacy and Safety Results in Complement Inhibitor-Naive
Patients with Paroxysmal Nocturnal Hemoglobinuria. Poster presentation at
European Hematology Association (EHA) Annual Congress; 2023 June 08-13. Abstract
#P785.
(10)COMMUTE-p (NCT04958265). (Internet; cited June 2024) Available at:
https://www.clinicaltrials.gov/ct2/show/NCT04958265.
(11)COMMUTE-a (NCT04861259). (Internet; cited June 2024) Available at:
https://www.clinicaltrials.gov/ct2/show/NCT04861259.
(12)Nishimura J, et al. Crovalimab for Treatment of Patients With Paroxysmal
NocturnalHemoglobinuria And Complement C5 Polymorphism - Experience From The
Composer Phase I/II Study. EHA Library. 2020; Abstract PB1992.
(13)CROSSWALK-a (NCT04912869) ClinicalTrials.gov. (Internet; cited June 2024).
Available at: https://clinicaltrials.gov/ct2/show/NCT04912869.
(14)CROSSWALK-c (NCT05075824) ClinicalTrials.gov. (Internet; cited June 2024).
Available at: https://clinicaltrials.gov/ct2/show/NCT05075824.
Roche Global Media Relations
Phone: +41 61 688 8888 / e-mail: media.relations@roche.com
(mailto:media.relations@roche.com)

  Hans Trees, PhD           Sileia Urech
  Phone: +41 79 407 72 58   Phone: +41 79 935 81 48
  Nathalie Altermatt        Simon Goldsborough
  Phone: +41 79 771 05 25   Phone: +44 797 32 72 915
  Karsten Kleine            Nina Mählitz
  Phone: +41 79 461 86 83   Phone: +41 79 327 54 74
  Kirti Pandey              Yvette Petillon
  Phone: +49 172 6367262    Phone: +41 79 961 92 50
  Dr. Rebekka Schnell
  Phone: +41 79 205 27 03

Roche Investor Relations

 Dr. Bruno Eschli                        Dr. Sabine Borngräber
 Phone: +41 61 68-75284                  Phone: +41 61 68-88027
 e-mail: bruno.eschli@roche.com          e-mail: sabine.borngraeber@roche.com
 (mailto:bruno.eschli@roche.com)         (mailto:sabine.borngraeber@roche.com)

Dr. Birgit Masjost
Phone: +41 61 68-84814
e-mail: birgit.masjost@roche.com
(mailto:birgit.masjost@roche.com)
Investor Relations North America

  Loren Kalm
  Phone: +1 650 225 3217

e-mail: kalm.loren@gene.com (mailto:kalm.loren@gene.com)Â