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New Genentech Data at the 2019 AAN Annual Meeting Showcase Breadth and Promise of Neuroscience Portfolio

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The logo of Swiss pharmaceutical company Roche is seen outside their headquarters in Basel, January 30, 2014.

SOUTH SAN FRANCISCO, Calif.–(BUSINESS WIRE)–Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY),
announced today that new data for its approved and investigational
medicines for the treatment of neurological conditions will be presented
at the 71st American Academy of Neurology (AAN) Annual Meeting from May
4-10 in Philadelphia, PA. Presentations include data from a pivotal
study for risdiplam in spinal muscular atrophy (SMA), which has the
potential to become the first oral treatment for this community. New
research for OCREVUS® (ocrelizumab) in relapsing and primary
progressive multiple sclerosis shows that its effect on reducing the
risk of disability progression is associated with higher exposure and
lower B-cell levels. Additional OCREVUS data demonstrate the importance
of earlier treatment. New data for investigational medicines in
neuromyelitis optica spectrum disorder (NMOSD), Huntington’s disease
(HD), Alzheimer’s disease (AD) and Duchenne muscular dystrophy (DMD)
will also be shared.

“The great need for therapeutic options in areas of neuroscience such as
SMA, HD and NMOSD means that every development is a collective step
forward,” said Sandra Horning, M.D., chief medical officer and head of
Global Product Development. “We continue to invest in research and
partnerships to develop new treatment options for these diseases that
severely reduce quality of life. We are pleased to contribute to the
greater understanding and clinical progress of neurologic diseases at
this year’s AAN Annual Meeting to help make a difference in the lives of
people and families impacted by these conditions.”

Spinal Muscular Atrophy (SMA)

New data will be presented for risdiplam, an investigational oral
survival motor neuron 2 (SMN2) splicing modifier for SMA, which is
designed to increase and sustain SMN protein levels in the central
nervous system (CNS) and throughout the body. Platform presentations
include one-year data from the dose-finding Part 1 of the pivotal
FIREFISH study on key motor milestones, motor function and survival in
infants with Type 1 SMA. Updated safety, tolerability and
pharmacokinetics / pharmacodynamics (PK/PD) data, as well as an
exploratory efficacy analysis from Part 1 of the pivotal SUNFISH study
in people aged 2-25 years with SMA Types 2 or 3 will also be presented.

Multiple Sclerosis (MS)

New analyses in relapsing and primary progressive multiple sclerosis
suggest that higher OCREVUS exposure and lower B-cell levels are
important for control of disability progression. Additionally, new
long-term data from the Phase III OPERA and ORATORIO open-label
extension trials showed earlier treatment with OCREVUS significantly
reduced the risk of permanent disability progression. Updated safety
data being presented remain consistent with findings from the controlled
Phase III trials, supporting OCREVUS’ favorable benefit-risk profile.

Neuromyelitis Optica Spectrum Disorder (NMOSD)

A subgroup analysis based on AQP4-Ig serostatus from the pivotal Phase
III SAkuraSky trial investigating satralizumab compared to placebo as
add-on to baseline immunosuppressants and/or corticosteroids for the
treatment of NMOSD will be presented. The subgroup data shows that
satralizumab significantly reduced the risk of NMOSD relapse in a
clinically-relevant population, especially in AQP4-Ig positive patients,
with a favorable benefit-risk profile. The Phase III trial SAkuraStar,
investigating satralizumab compared to placebo as a monotherapy, met its
primary endpoint and will be presented at a future congress.

Satralizumab is a humanized IgG2 anti-human interleukin-6 (IL-6)
receptor neutralizing monoclonal antibody that represents a novel
approach to treating NMOSD by selectively inhibiting the inflammatory
effects of IL-6, thought to be a key driver in the pathogenesis of the
disease. There are currently no approved treatments for NMOSD, a rare,
lifelong and debilitating autoimmune disease of the central nervous
system that damages the optic nerve and spinal cord, causing blindness,
muscle weakness and paralysis.

Huntington’s Disease (HD)

The HD platform session will include results from a translational
modeling approach developed from preclinical data and includes clinical
RG6042 data from the ongoing, open-label extension study in HD patients,
including a safety update and mutant huntingtin (mHTT) protein reduction
in the cerebrospinal fluid. These data also support the dose selection
for the recently initiated Phase III GENERATION HD1 clinical trial
investigating RG6042 in manifest HD.

RG6042 (formerly known as Ionis HTT-Rx) is an antisense oligonucleotide
(ASO) designed to reduce the production of the toxic mHTT protein, the
disease-causing protein in people with HD, by targeting human huntingtin
RNA.

Alzheimer’s disease (AD)

Data and safety findings from the gantenerumab SCarlet RoAD and
Marguerite RoAD open-label extension studies will be presented that show
consistently large amyloid reductions in AD patients with and without
ARIA-E. Genentech continues to advance the development of gantenerumab
in the Phase III GRADUATE trials and the anti-tau molecule RO7105705
(MTAU9937A, RG6100) into its second Phase II clinical trial (LAURIET),
which is currently enrolling patients with moderate AD.

The study design, methodology and baseline characteristics from the
crenezumab Phase III CREAD study will be presented in a poster at AAN.
Data from the crenezumab interim analysis of the now discontinued CREAD
program were presented at the 14th International Conference on
Alzheimer’s & Parkinson’s Diseases in March 2019. Additional analyses,
including biomarker data, will be presented at future medical
conferences. Crenezumab continues to be studied in a landmark
Alzheimer’s Prevention Initiative trial of cognitively healthy
individuals in Colombia with an autosomal dominant mutation who are at
risk to develop familial AD (fAD).

Duchenne Muscular Dystrophy (DMD)

Results will be shared from a Phase Ib/II study of the anti-myostatin
adnectin RG6206 in ambulatory boys with DMD showing no drug-related
safety findings leading to withdrawal from the study through 72 weeks of
treatment. RG6042 successfully lowered myostatin levels in the blood of
boys with DMD and MRI and DXA imaging suggested that RG6206 had a
positive effect on muscle in boys with DMD.

Stroke

Genentech recently initiated the Phase III TIMELESS trial to evaluate
TNKase® (tenecteplase) in people with acute ischemic stroke
(AIS) when treated from four and a half up to 24 hours after the onset
of symptoms and using advanced imaging technology to identify eligible
patients. There are currently no FDA approved medicines for people with
AIS beyond three hours after the onset of symptoms.

Genentech’s 23-year history in AIS was established with Activase®
(alteplase), the current standard-of-care in the United States, and the
first and only clot-dissolving tissue plasminogen activator (tPA)
approved for use in AIS for up to three hours after the onset of
symptoms.

The full range of data from Genentech’s late-stage clinical development
program in neuroscience being presented at AAN include:

Medicine Abstract Title

Presentation Number
(type), Presentation
Date,
Time
Risdiplam for Spinal Muscular Atrophy FIREFISH Part 1: 1-year Results on Motor Function in Babies with
Type 1 SMA Receiving Risdiplam (RG7916)

S25.003 (platform),
Tuesday, May 7,
1:22 – 1:33 p.m. EDT
Update from SUNFISH Part 1: Safety, Tolerability and PK/PD from the
Dose-finding Study, Including Exploratory Efficacy Data in Patients
with Type 2 or 3 Spinal Muscular Atrophy (SMA) Treated with
Risdiplam (RG7916)

S25.007 (platform),
Tuesday, May 7,
2:06 – 2:17 p.m. EDT
FIREFISH Part 1: Survival, Ventilation and Swallowing Ability in
Infants with Type 1 SMA Receiving Risdiplam (RG7916)

S25.008 (platform),
Tuesday, May 7,
2:17 – 2:28 p.m. EDT
OCREVUS (ocrelizumab) for Multiple Sclerosis Reduction in 48-Week Confirmed Disability Progression After 5.5
Years of Ocrelizumab Treatment in Patients with Primary Progressive
Multiple Sclerosis

P3.2-031 (poster),
Tuesday, May 7,
5:30 – 6:30 p.m. EDT
Long-Term Reduction in 48-Week Confirmed Disability Progression
After 5 Years of Ocrelizumab Treatment in Patients with Relapsing
Multiple Sclerosis

P3.2-054 (poster),
Tuesday, May 7,
5:30 – 6:30 p.m. EDT
Evaluation of Shorter Infusion Times with Ocrelizumab in Patients
with Relapsing-Remitting Multiple Sclerosis

P3.2-034 (poster),
Tuesday, May 7,
5:30 – 6:30 p.m. EDT
Ocrelizumab Treatment Effect on Upper Limb Function in PPMS Patients
with Disability: Subgroup Results of the ORATORIO Study to Inform
the ORATORIO-HAND Study Design

P3.2-091 (poster),
Tuesday, May 7,
5:30 – 6:30 p.m. EDT
Reduced Rate of Brain Atrophy in Patients with PPMS Receiving
Ocrelizumab Earlier and Continuously Versus Those Initiating
Ocrelizumab Later: Results of ORATORIO 5-Year Follow-Up

P3.2-042 (poster),
Tuesday, May 7,
5:30 – 6:30 p.m. EDT
FLOODLIGHT: Smartphone-Based Self-Monitoring Is Accepted by Patients
and Provides Meaningful, Continuous Digital Outcomes Augmenting
Conventional In-Clinic Multiple Sclerosis Measures

P3.2-024 (poster),
Tuesday, May 7,
5:30 – 6:30 p.m. EDT
Pharmacokinetics, Pharmacodynamics and Exposure-Response Analyses of
Ocrelizumab in Patients with Multiple Sclerosis

N4.001 (platform),
Wednesday, May 8,
2:00 – 2:15 p.m. EDT
VERISMO: A Post-Marketing Safety Study to Determine the Incidence of
All Malignancies and Breast Cancer in Patients with Multiple
Sclerosis Treated with Ocrelizumab

P4.2-043 (poster),
Wednesday, May 8,
5:30 – 6:30 p.m. EDT
Safety of Ocrelizumab in Multiple Sclerosis: Updated Analysis in
Patients with Relapsing and Primary Progressive Multiple Sclerosis

P4.2-025 (poster),
Wednesday, May 8,
5:30 – 6:30 p.m. EDT
One-Year Interim Analysis Results of the Phase IIIb CHORDS Study
Evaluating Ocrelizumab Effectiveness and Safety in Patients with
Relapsing-Remitting Multiple Sclerosis Who Had Suboptimal Response
with Prior Disease-Modifying Treatments

S56.007 (platform),
Friday, May 10,
2:06 – 2:17 p.m. EDT
Ocrelizumab Treatment Reduced Levels of Neurofilament Light Chain
and Numbers of B cells in the Cerebrospinal Fluid of Patients with
Relapsing Multiple Sclerosis in the OBOE Study

S56.008 (platform),
Friday, May 10,
2:17 – 2:28 p.m. EDT
Satralizumab for Neuromyelitis Optica Spectrum Disorder Efficacy of Satralizumab (SA237) in Subgroups of Patients in
SAkuraSky: A Phase III Double-Blind, Placebo-Controlled, Add-On
Study in Patients with Neuromyelitis Optica Spectrum Disorder (NMOSD)

S43.008 (platform),
Wednesday, May 8,
4:47 – 4:58 p.m.
EDT
RG6042 for Huntington’s Disease Preliminary Reliability and Validity of a Novel Digital Biomarker
Smartphone Application to Assess Cognitive and Motor Symptoms in
Huntington’s Disease

P1.8-042 (poster),
Sunday, May 5,
5:30 – 6:30 p.m. EDT
Defining Clinically Meaningful Change on the Composite Unified
Huntington’s Disease Rating Scale (cUHDRS)

P1.8-043 (poster),
Sunday, May 5,
5:30 – 6:30 p.m. EDT
Translational Pharmacokinetic/Pharmacodynamic (PK/PD) Modelling
Strategy to Support RG6042 Dose Selection in Huntington’s Disease

S16.005 (platform),
Monday, May 6,
1:44 – 1:54 p.m. EDT
Gantenerumab for Alzheimer’s Disease Consistently Large Amyloid Reductions in Patients with and Without
ARIA-E in the Gantenerumab SCarlet RoAD and Marguerite RoAD
Open-Label Extension Studies

S9.007 (platform),
Sunday, May 5,
4:36 – 4:47 p.m. EDT
Crenezumab for Alzheimer’s Disease Baseline Characteristics from a Phase III Trial of Crenezumab in
Early (Prodromal-to Mild) Alzheimer’s Disease (CREAD)

P4.1-002 (poster)
Wednesday, May 8,
5:30 – 6:30 p.m. EDT
RG6206 for Duchenne Muscular Dystrophy A Phase 1b/2 Study of the Anti-Myostatin Adnectin RG6206
(BMS-986089) in Ambulatory Boys with Duchenne Muscular Dystrophy: A
72-Week Treatment Update

P1.6-062 (poster),
Sunday, May 5,
5:30 – 6:30 p.m. EDT

Full session details and data presentation listings for the 2019 AAN
Annual Meeting can be found at the meeting website: https://www.aan.com/conferences-community/annual-meeting/.

Follow Genentech on Twitter via @Genentech and keep up to date with AAN
2019 Annual Meeting news and updates by using the hashtag #AANAM.

About OCREVUS® (ocrelizumab)

OCREVUS is a humanized monoclonal antibody designed to target
CD20-positive B cells, a specific type of immune cell thought to be a
key contributor to myelin (nerve cell insulation and support) and axonal
(nerve cell) damage. This nerve cell damage can lead to disability in
people with multiple sclerosis (MS). Based on preclinical studies,
OCREVUS binds to CD20 cell surface proteins expressed on certain B
cells, but not on stem cells or plasma cells, and therefore important
functions of the immune system may be preserved.

OCREVUS is administered by intravenous infusion every six months. The
initial dose is given as two 300 mg infusions given two weeks apart.
Subsequent doses are given as single 600 mg infusions.

Important Safety Information

What is OCREVUS?

OCREVUS is a prescription medicine used to treat adults with relapsing
or primary progressive forms of multiple sclerosis.

It is not known if OCREVUS is safe or effective in children.

Who should not receive OCREVUS?

Do not receive OCREVUS if you have an active hepatitis B virus
(HBV) infection.

Do not receive OCREVUS if you have had a life threatening
allergic reaction to OCREVUS. Tell your healthcare provider if you have
had an allergic reaction to OCREVUS or any of its ingredients in the
past.

What is the most important information I should know about OCREVUS?

OCREVUS can cause serious side effects, including:

These infusion reactions can happen for up to 24 hours after your
infusion. It is important that you call your healthcare provider
right away if you get any of the signs or symptoms listed above after
each infusion.

If you get infusion reactions, your healthcare provider may need to stop
or slow down the rate of your infusion.

Before receiving OCREVUS, tell your healthcare provider about all of
your medical conditions, including if you:

Tell your healthcare provider about all the medicines you take, including
prescription and over-the-counter medicines, vitamins, and herbal
supplements.

What are the possible side effects of OCREVUS?

OCREVUS may cause serious side effects, including:

Most common side effects include infusion reactions and infections.

These are not all the possible side effects of OCREVUS. Call your doctor
for medical advice about side effects. You may report side effects to
FDA at 1-800-FDA-1088.

For additional safety information, please see the OCREVUS full
Prescribing Information and Medication Guide.

For more information, go to https://www.OCREVUS.com
or call 1-844-627-3887.

About TNKase®

Indication

TNKase® (tenecteplase) is indicated for use in the reduction
of mortality associated with acute myocardial infarction (AMI).
Treatment should be initiated as soon as possible after the onset of AMI
symptoms.

Important Safety Information

Contraindications

TNKase therapy in patients with AMI is contraindicated in the following
situations because of an increased risk of bleeding: active internal
bleeding; history of cerebrovascular accident; intracranial or
intraspinal surgery, or trauma within 2 months; intracranial neoplasm,
arteriovenous malformation, or aneurysm; known bleeding diathesis; and
severe uncontrolled hypertension.

Warnings

Bleeding

The most common complication encountered during TNKase therapy is
bleeding. Should serious bleeding (not controlled by local pressure)
occur, any concomitant heparin or antiplatelet agents should be
discontinued immediately.

In clinical studies of TNKase, patients were treated with both aspirin
and heparin. Heparin may contribute to the bleeding risks associated
with TNKase. The safety of the use of TNKase with other antiplatelet
agents has not been adequately studied. Intramuscular injections and
nonessential handling of the patient should be avoided for the first few
hours following treatment with TNKase.

The risk of bleeding may be increased in the following conditions and
should be weighed against the anticipated benefits: recent major
surgery, cerebrovascular disease, recent gastrointestinal or
genitourinary bleeding, recent trauma, hypertension, high likelihood of
left heart thrombus, acute pericarditis, subacute bacterial
endocarditis, hemostatic defects, severe hepatic dysfunction, pregnancy,
diabetic hemorrhagic retinopathy or other hemorrhagic ophthalmic
conditions, septic thrombophlebitis or occluded AV cannula at seriously
infected site, advanced age, patients currently receiving oral
anticoagulants, recent administration of GP IIb/IIIa inhibitors, and any
other condition in which bleeding constitutes a significant hazard or
would be particularly difficult to manage because of its location.

Cholesterol Embolization

Cholesterol embolism has been reported rarely in patients treated with
all types of thrombolytic agents; the true incidence is unknown. This
serious condition, which can be lethal, is also associated with invasive
vascular procedures (e.g., cardiac catheterization, angiography,
vascular surgery) and/or anticoagulant therapy.

Arrhythmias

Coronary thrombolysis may result in arrhythmias associated with
reperfusion. It is recommended that anti-arrhythmic therapy for
bradycardia and/or ventricular irritability be available when TNKase is
administered.

Use with Percutaneous Coronary Intervention (PCI)

In patients with large ST-segment elevation myocardial infarction,
physicians should choose either thrombolysis or PCI as the primary
treatment strategy for reperfusion.

Precautions

Standard management of myocardial infarction should be implemented
concomitantly with TNKase treatment.

Pregnancy (Category C)

There are no adequate and well-controlled studies in pregnant women.
TNKase should be given to pregnant women only if the potential benefits
justify the potential risk to the fetus.

Nursing Mothers

It is not known if TNKase is excreted in human milk. Because many drugs
are excreted in human milk, caution should be exercised when TNKase is
administered to a nursing woman.

Geriatric Use

In elderly patients, the benefits of TNKase on mortality should be
carefully weighed against the risk of increased adverse events,
including bleeding.

Adverse Reactions

The most frequent adverse reaction associated with TNKase is bleeding.

Should serious bleeding occur, concomitant heparin and antiplatelet
therapy should be discontinued. Death or permanent disability can occur
in patients who experience stroke or serious bleeding episodes.

For TNKase-treated patients in ASSENT-2, the incidence of intracranial
hemorrhage was 0.

Contacts

Media Contact:
Kimberly Muscara (650) 467-6800

Advocacy Contact:
Jo Dulay (202) 316-6304

Investor Contact:
Loren Kalm (650) 225-3217
Karl Mahler 011 41
61 687 8503

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