Genmab — Regulatory Filings 2017

Jun 16, 2017

Company Announcement

-- DARZALEX (daratumumab) approved by U.S. FDA in combination with
pomalidomide and dexamethasone for patients with multiple myeloma who have
received at least two prior therapies including lenalidomide and a
proteasome inhibitor
-- Genmab to receive milestone payments totaling USD 25 million

Copenhagen, Denmark; June 16, 2017 – Genmab A/S (Nasdaq Copenhagen: GEN)
announced today the U.S. Food and Drug Administration (FDA) has approved the
use of DARZALEX® (daratumumab) in combination with pomalidomide and
dexamethasone for the treatment of patients with multiple myeloma who have
received at least two prior therapies including lenalidomide and a proteasome
inhibitor. DARZALEX is being developed under an August 2012 agreement in which
Genmab granted Janssen Biotech, Inc. an exclusive worldwide license to develop,
manufacture and commercialize the product. Genmab will receive milestone
payments totaling USD 25 million from Janssen in connection with the approval
and first commercial sale of DARZALEX under the newly expanded label. The sale
is expected to occur quickly after the approval. The approval and related
milestones do not impact the financial guidance issued by Genmab on May 10,
2017.

“We are very pleased to receive the FDA’s decision to approve DARZALEX in
combination with pomalidomide and dexamethasone. This offers another
alternative to patients with multiple myeloma who haven’t seen lasting effects
from other types of treatment,” said Jan van de Winkel, Ph.D., Chief Executive
Officer of Genmab.

The approval was based on data from the Phase I (MMY1001, EQUULEUS) study of
daratumumab in combination with pomalidomide and dexamethasone in relapsed or
refractory multiple myeloma.

About the EQUULEUS study
The Phase I EQUULEUS open-label study, Pom-D arm, included 103 patients with
multiple myeloma who had received prior treatment with a proteasome inhibitor
(PI) and an immunomodulatory agent. Patients in the study received 16 mg/kg
daratumumab in combination with pomalidomide and dexamethasone. The overall
response rate in the study was 59% (95% CI: 49.1%, 68.8%), with very good
partial response (VGPR) achieved in 28% of patients. Complete response (CR) was
achieved in 6% of patients and stringent CR (sCR) was achieved in 8% of
patients. The median time to response was 1 month (range: 0.9 to 2.8 months).
The median duration of response was 13.6 months (range: 0.9+ to 14.6+ months).
The most frequent adverse reactions (>20%) in the study were: infusion
reactions (50%), diarrhea (38%), nausea (30%), vomiting (21%), fatigue (50%),
pyrexia (25%), upper respiratory tract infection (50%), muscle spasms (26%),
cough (43%) and dyspnea (33%). The overall incidence of serious adverse
reactions was 49%. Serious adverse reactions (Grade 3/4) reported in ?5%
patients included pneumonia (7%). The most common treatment-emergent hematology
laboratory abnormalities were lymphopenia (94%), neutropenia (95%),
thrombocytopenia (75%) and anemia (57%). The most common Grade 3/4
treatment-emergent hematology laboratory abnormalities were neutropenia (82%),
lymphopenia (71%), anemia (30%) and thrombocytopenia (20%).

The median age of patients in the study was 64 years with 8% of patients older
than 75. Patients in the study had received a median of four prior lines of
therapy, and 74% of patients had received prior autologous stem cell transplant
(ASCT). Eighty-nine percent of patients were refractory to lenalidomide and 71%
were refractory to bortezomib; 64% of patients were refractory to bortezomib
and lenalidomide.

About multiple myeloma
Multiple myeloma is an incurable blood cancer that starts in the bone marrow
and is characterized by an excess proliferation of plasma cells.1 Multiple
myeloma is the third most common blood cancer in the U.S., after leukemia and
lymphoma.2 Approximately 30,330 new patients were expected to be diagnosed with
multiple myeloma and approximately 12,650 people were expected to die from the
disease in the U.S. in 2016.3 Globally, it was estimated that 124,225 people
would be diagnosed and 87,084 would die from the disease in 2015.4 While some
patients with multiple myeloma have no symptoms at all, most patients are
diagnosed due to symptoms which can include bone problems, low blood counts,
calcium elevation, kidney problems or infections.5 Patients who relapse after
treatment with standard therapies, including proteasome inhibitors or
immunomodulatory agents, have poor prognoses and few treatment options.6

About DARZALEX® (daratumumab)
DARZALEX® (daratumumab) injection for intravenous infusion is indicated in the
United States in combination with lenalidomide and dexamethasone, or bortezomib
and dexamethasone, for the treatment of patients with multiple myeloma who have
received at least one prior therapy; in combination with pomalidomide and
dexamethasone for the treatment of with multiple myeloma who have received at
least two prior therapies, including lenalidomide and a proteasome inhibitor
(PI); and as a monotherapy for the treatment of patients with multiple myeloma
who have received at least three prior lines of therapy, including a PI and an
immunomodulatory agent, or who are double-refractory to a PI and an
immunomodulatory agent.7 DARZALEX is the first monoclonal antibody (mAb) to
receive U.S. Food and Drug Administration (FDA) approval to treat multiple
myeloma. DARZALEX is indicated in Europe for use in combination with
lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the
treatment of adult patients with multiple myeloma who have received at least
one prior therapy and as monotherapy for the treatment of adult patients with
relapsed and refractory multiple myeloma, whose prior therapy included a PI and
an immunomodulatory agent and who have demonstrated disease progression on the
last therapy. DARZALEX is the first human CD38 monoclonal antibody approved in
Europe. For more information, visit www.DARZALEX.com.

Daratumumab is a human IgG1k monoclonal antibody (mAb) that binds with high
affinity to the CD38 molecule, which is highly expressed on the surface of
multiple myeloma cells. Daratumumab triggers a person’s own immune system to
attack the cancer cells, resulting in rapid tumor cell death through multiple
immune-mediated mechanisms of action and through immunomodulatory effects, in
addition to direct tumor cell death, via apoptosis (programmed cell death).
7,8,9,10,11

Daratumumab is being developed by Janssen Biotech, Inc. under an exclusive
worldwide license to develop, manufacture and commercialize daratumumab from
Genmab. Five Phase III clinical studies with daratumumab in relapsed and
frontline multiple myeloma settings are currently ongoing, and additional
studies are ongoing or planned to assess its potential in other malignant and
pre-malignant diseases on which CD38 is expressed, such as smoldering myeloma,
NKT-cell lymphoma, amyloidosis, myelodysplastic syndromes and solid tumors.
Daratumumab has received two Breakthrough Therapy Designations from the U.S.
FDA, for multiple myeloma, as both a monotherapy and in combination with other
therapies.

IMPORTANT SAFETY INFORMATION
CONTRAINDICATIONS - None

WARNINGS AND PRECAUTIONS
Infusion Reactions – DARZALEX® can cause severe infusion reactions.
Approximately half of all patients experienced a reaction, most during the
first infusion. Infusion reactions can also occur with subsequent infusions.
Nearly all reactions occurred during infusion or within 4 hours of completing
an infusion. Prior to the introduction of post-infusion medication in clinical
trials, infusion reactions occurred up to 48 hours after infusion. Severe
reactions have occurred, including bronchospasm, hypoxia, dyspnea,
hypertension, laryngeal edema and pulmonary edema. Signs and symptoms may
include respiratory symptoms, such as nasal congestion, cough, throat
irritation, as well as chills, vomiting and nausea. Less common symptoms were
wheezing, allergic rhinitis, pyrexia, chest discomfort, pruritus, and
hypotension.

Pre-medicate patients with antihistamines, antipyretics, and corticosteroids.
Frequently monitor patients during the entire infusion. Interrupt infusion for
reactions of any severity and institute medical management as needed.
Permanently discontinue therapy for life-threatening (Grade 4) reactions. For
patients with Grade 1, 2, or 3 reactions, reduce the infusion rate when
re-starting the infusion.

To reduce the risk of delayed infusion reactions, administer oral
corticosteroids to all patients following DARZALEX infusions. Patients with a
history of chronic obstructive pulmonary disease may require additional
post-infusion medications to manage respiratory complications. Consider
prescribing short- and long-acting bronchodilators and inhaled corticosteroids
for patients with chronic obstructive pulmonary disease.

Interference with Serological Testing - Daratumumab binds to CD38 on red blood
cells (RBCs) and results in a positive Indirect Antiglobulin Test (Indirect
Coombs test). Daratumumab-mediated positive indirect antiglobulin test may
persist for up to 6 months after the last daratumumab infusion. Daratumumab
bound to RBCs masks detection of antibodies to minor antigens in the patient’s
serum. The determination of a patient’s ABO and Rh blood type are not impacted.
Notify blood transfusion centers of this interference with serological testing
and inform blood banks that a patient has received DARZALEX. Type and screen
patients prior to starting DARZALEX.

Neutropenia - DARZALEX may increase neutropenia induced by background therapy.
Monitor complete blood cell counts periodically during treatment according to
manufacturer’s prescribing information for background therapies. Monitor
patients with neutropenia for signs of infection. DARZALEX dose delay may be
required to allow recovery of neutrophils. No dose reduction of DARZALEX is
recommended. Consider supportive care with growth factors.

Thrombocytopenia - DARZALEX may increase thrombocytopenia induced by background
therapy. Monitor complete blood cell counts periodically during treatment
according to manufacturer’s prescribing information for background therapies.
DARZALEX dose delay may be required to allow recovery of platelets. No dose
reduction of DARZALEX is recommended. Consider supportive care with
transfusions.

Interference with Determination of Complete Response - Daratumumab is a human
IgG kappa monoclonal antibody that can be detected on both, the serum protein
electrophoresis (SPE) and immunofixation (IFE) assays used for the clinical
monitoring of endogenous M-protein. This interference can impact the
determination of complete response and of disease progression in some patients
with IgG kappa myeloma protein.

Adverse Reactions – In patients who received DARZALEX in combination with
lenalidomide and dexamethasone, the most frequently reported adverse reactions
(incidence ?20%) were: neutropenia (92%), thrombocytopenia (73%), upper
respiratory tract infection (65%), infusion reactions (48%), diarrhea (43%),
fatigue (35%), cough (30%), muscle spasms (26%), nausea (24%), dyspnea (21%)
and pyrexia (20%). The overall incidence of serious adverse events was 49%.
Serious adverse reactions were pneumonia (12%), upper respiratory tract
infection (7%), influenza (3%) and pyrexia (3%).

In patients who received DARZALEX in combination with bortezomib and
dexamethasone, the most frequently reported adverse reactions (incidence >20%)
were: thrombocytopenia (90%), neutropenia (58%), peripheral sensory neuropathy
(47%), infusion reactions (45%), upper respiratory tract infection (44%),
diarrhea (32%), cough (27%), peripheral edema (22%), and dyspnea (21%). The
overall incidence of serious adverse events was 42%. Serious adverse reactions
were upper respiratory tract infection (5%), diarrhea (2%) and atrial
fibrillation (2%).

In patients who received DARZALEX in combination with pomalidomide and
dexamethasone, the most frequently reported adverse reactions (incidence >20%)
were: infusion reactions (50%), diarrhea (38%), nausea (30%), vomiting (21%),
fatigue (50%), pyrexia (25%), upper respiratory tract infection (50%), muscle
spasms (26%), cough (43%) and dyspnea (33%). The overall incidence of serious
adverse reactions was 49%. Serious adverse reactions (Grade 3/4) reported in
?5% patients included pneumonia (7%). The most common treatment-emergent
hematology laboratory abnormalities were lymphopenia (94%), neutropenia (95%),
thrombocytopenia (75%) and anemia (57%). The most common Grade 3/4
treatment-emergent hematology laboratory abnormalities were neutropenia (82%),
lymphopenia (71%), anemia (30%) and thrombocytopenia (20%).

In patients who received DARZALEX as monotherapy, the most frequently reported
adverse reactions (incidence ?20%) were: neutropenia (60%), thrombocytopenia
(48%), infusion reactions (48%), fatigue (39%), nausea (27%), back pain (23%),
pyrexia (21%), cough (21%), and upper respiratory tract infection (20%).
Serious adverse reactions were reported in 51 (33%) patients. The most frequent
serious adverse reactions were pneumonia (6%), general physical health
deterioration (3%), and pyrexia (3%).

DRUG INTERACTIONS
Effect of Other Drugs on daratumumab: The coadministration of lenalidomide,
pomalidomide or bortezomib with DARZALEX did not affect the pharmacokinetics of
daratumumab.

Effect of Daratumumab on Other Drugs: The coadministration of DARZALEX with
bortezomib did not affect the pharmacokinetics of bortezomib.

About Genmab
Genmab is a publicly traded, international biotechnology company specializing
in the creation and development of differentiated antibody therapeutics for the
treatment of cancer. Founded in 1999, the company has two approved antibodies,
DARZALEX® (daratumumab) for the treatment of certain multiple myeloma
indications, and Arzerra® (ofatumumab) for the treatment of certain chronic
lymphocytic leukemia indications. Daratumumab is in clinical development for
additional multiple myeloma indications, other blood cancers, and solid tumors.
A subcutaneous formulation of ofatumumab is in development for relapsing
multiple sclerosis. Genmab also has a broad clinical and pre-clinical product
pipeline. Genmab's technology base consists of validated and proprietary next
generation antibody technologies - the DuoBody® platform for generation of
bispecific antibodies, and the HexaBody® platform which creates effector
function enhanced antibodies. The company intends to leverage these
technologies to create opportunities for full or co-ownership of future
products. Genmab has alliances with top tier pharmaceutical and biotechnology
companies. For more information visit www.genmab.com.

Contact:
Rachel Curtis Gravesen, Senior Vice President, Investor Relations &
Communications
T: +45 33 44 77 20; M: +45 25 12 62 60; E: r.gravesen@genmab.com

This Company Announcement contains forward looking statements. The words
“believe”, “expect”, “anticipate”, “intend” and “plan” and similar expressions
identify forward looking statements. Actual results or performance may differ
materially from any future results or performance expressed or implied by such
statements. The important factors that could cause our actual results or
performance to differ materially include, among others, risks associated with
pre-clinical and clinical development of products, uncertainties related to the
outcome and conduct of clinical trials including unforeseen safety issues,
uncertainties related to product manufacturing, the lack of market acceptance
of our products, our inability to manage growth, the competitive environment in
relation to our business area and markets, our inability to attract and retain
suitably qualified personnel, the unenforceability or lack of protection of our
patents and proprietary rights, our relationships with affiliated entities,
changes and developments in technology which may render our products obsolete,
and other factors. For a further discussion of these risks, please refer to the
risk management sections in Genmab’s most recent financial reports, which are
available on www.genmab.com. Genmab does not undertake any obligation to update
or revise forward looking statements in this Company Announcement nor to
confirm such statements in relation to actual results, unless required by law.

Genmab A/S and its subsidiaries own the following trademarks: Genmab®; the
Y-shaped Genmab logo®; Genmab in combination with the Y-shaped Genmab logo™;
the DuoBody logo®; the HexaBody logo™; HuMax®; HuMax-CD20®; DuoBody®; HexaBody®
and UniBody®. Arzerra® is a trademark of Novartis AG or its affiliates.
DARZALEX® is a trademark of Janssen Biotech, Inc.

1 American Cancer Society. "Multiple Myeloma Overview." Available at
http://www.cancer.org/cancer/multiplemyeloma/detailedguide/multiple-myeloma-what
-is-multiple-myeloma.Accessed
June 2016.
2 National Cancer Institute. "A Snapshot of Myeloma." Available at
www.cancer.gov/research/progress/snapshots/myeloma. Accessed June 2016.
3 American Cancer Society. "What are the key statistics about multiple
myeloma?"
http://www.cancer.org/cancer/multiplemyeloma/detailedguide/multiple-myeloma-key-
statistics.
Accessed June 2016.
4 GLOBOCAN 2012: Estimated Cancer Incidence, Mortality and Prevalence
Worldwide: Number of New Cancers in 2015. Available at:
http://globocan.iarc.fr/old/burden.asp?selection_pop=224900&Text-p=World&selecti
on_cancer=17270&Text-c=Multiple+myeloma&pYear=3&type=0&window=1&submit=%C2%A0Exe
cute.
Accessed June 2016.
5 American Cancer Society. "How is Multiple Myeloma Diagnosed?"
http://www.cancer.org/cancer/multiplemyeloma/detailedguide/multiple-myeloma-diag
nosis.
Accessed June 2016.
6 Kumar, SK et al. Risk of progression and survival in multiple myeloma
relapsing after last therapy with IMiDs and bortezomib: a multicenter
international myeloma working group study. Leukemia. 2012; 26:149-57.
7 DARZALEX Prescribing information, June 2017. Available at:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/761036s004lbl.pdf.
Last accessed June 2017.
8 De Weers, M et al. Daratumumab, a Novel Therapeutic Human CD38 Monoclonal
Antibody, Induces Killing of Multiple Myeloma and Other Hematological Tumors.
The Journal of Immunology. 2011; 186: 1840-1848.
9 Overdijk, MB, et al. Antibody-mediated phagocytosis contributes to the
anti-tumor activity of the therapeutic antibody daratumumab in lymphoma and
multiple myeloma. MAbs. 2015; 7: 311-21.
10 Krejcik, MD et al. Daratumumab Depletes CD38+ Immune-regulatory Cells,
Promotes T-cell Expansion, and Skews T-cell Repertoire in Multiple Myeloma.
Blood. 2016; 128: 384-94.
11 Jansen, JH et al. Daratumumab, a human CD38 antibody induces apoptosis of
myeloma tumor cells via Fc receptor-mediated crosslinking. Blood. 2012;
120(21):abstract 2974.

Company Announcement no. 23
CVR no. 2102 3884
LEI Code 529900MTJPDPE4MHJ122

Genmab A/S
Bredgade 34E
1260 Copenhagen K
Denmark