Market Overview

Seattle Genetics and Astellas Announce Updated Enfortumab Vedotin Phase 1 Data in Metastatic Urothelial Cancer at 2017 ASCO Annual Meeting


Genetics, Inc.
(NASDAQ:SGEN) and Astellas
today highlighted updated phase 1 data for enfortumab vedotin (ASG-22ME)
studied as monotherapy treatment for metastatic urothelial cancer (mUC)
in an oral presentation at the American Society of Clinical Oncology
(ASCO) 52nd Annual Meeting in Chicago. Enfortumab vedotin is
an investigational antibody-drug conjugate (ADC) that targets Nectin-4,
a cell surface protein expressed in multiple solid tumors including mUC,
ovarian cancer, and non-small cell lung cancer (NSCLC). Based on the
data from the ongoing phase 1 clinical trial, the companies this year
plan to initiate a registrational monotherapy phase 2 trial for locally
advanced or mUC patients who have been previously treated with
checkpoint inhibitor (CPI) therapy. A trial evaluating enfortumab
vedotin in combination with CPIs is also planned for later this year as
part of a broad clinical development program.

This Smart News Release features multimedia. View the full release here:

"Patients with metastatic urothelial cancer typically have a five-year
survival rate of just five percent and are in urgent need of new
treatment options. Despite recent clinical advances, up to 80 percent of
patients fail to respond to checkpoint inhibitors, or CPIs, and there
are no approved therapeutic options for use after CPI failure," said
Daniel P. Petrylak, M.D., Ph.D., Yale Cancer Center and presenter of the
phase 1 data at ASCO. "The objective response rates observed in our
phase 1 analysis of enfortumab vedotin show the potential benefit of
this agent for patients with metastatic urothelial cancer, particularly
those who have failed CPI therapy. Enfortumab vedotin was generally
well-tolerated, and the most common adverse events were nausea, itching,
fatigue and diarrhea."

"Our updated enfortumab vedotin monotherapy phase 1 data at ASCO
continue to show encouraging antitumor activity and a well-tolerated
safety profile in patients with heavily pretreated metastatic urothelial
cancer. We plan to initiate this year a pivotal phase 2 study in the
CPI-pretreated setting with the intent of pursuing accelerated approval
from the FDA," said Jonathan Drachman, M.D., Chief Medical Officer and
Executive Vice President, Research and Development at Seattle Genetics.
"Enfortumab vedotin is our first late-stage clinical program for solid
tumors, and these data demonstrate the potential for antibody-drug
conjugates to provide therapeutic benefit across a wide array of

"We are encouraged by the data we've seen so far in the enfortumab
vedotin clinical trials," said Steven Benner, M.D., Senior Vice
President and Global Therapeutic Area Head, Oncology Development,
Astellas. "We're pleased to be moving forward the enfortumab vedotin
development program in support of patients who may benefit from this new
potential treatment option."

The following updated results from the ongoing phase 1 study evaluating
enfortumab vedotin as a monotherapy for mUC were presented by Dr.
Petrylak on Monday, June 5:

A Phase I Study of Enfortumab Vedotin (ASG-22CE; ASG-22ME): Updated
Analysis of Patients with Metastatic Urothelial Cancer (Abstract #106,
oral presentation on Monday, June 5 at 9:45 a.m. CT)

The ongoing trial is evaluating the safety and anti-tumor activity of
enfortumab vedotin at escalating doses of 0.5 to 1.25 milligrams per
kilogram (mg/kg) weekly for three of every four week cycles. Data were
reported from 81 patients diagnosed with mUC and a median age of 67
years. Of these patients, 37 (46 percent) were previously treated with
CPIs and 77 (95 percent) had undergone treatment with a platinum-based
chemotherapy. Ninety-seven percent of patient screening samples showed
Nectin-4 expression, the majority of which were at a high level. All
response rates include confirmed and unconfirmed responses, as assessed
by the investigator. The recommended phase 2 dose (RP2D) has been
established at 1.25 mg/kg. Key findings include:

  • Of the 71 patients evaluated for response, 29 patients (41 percent)
    had an objective response, including three (four percent) complete
    responses and 26 (37 percent) partial responses. Disease control was
    achieved in 51 patients (72 percent), defined as the sum of patients
    achieving complete responses, partial responses or stable disease. The
    preliminary estimate of median duration of response for all patients
    was 24 weeks.
  • In 30 patients treated at the RP2D level, 16 patients (53 percent) had
    an objective response, including one (three percent) complete response
    and 15 (50 percent) partial responses. Disease control was achieved
    for 22 patients (73 percent).
  • Of the 32 patients previously treated with CPIs and evaluated for
    response, 14 patients (44 percent) had an objective response,
    including one complete response (three percent) and 13 (41 percent)
    partial responses. At the RP2D, eight out of 17 CPI-treated patients
    (47 percent) achieved a partial response, and disease control occurred
    in 13 patients (77 percent).
  • Of the 19 patients with liver metastases, nine (47 percent) had an
    objective response, including one (five percent) complete response and
    eight (42 percent) partial responses. Disease control was achieved for
    13 patients (68 percent).
  • The most common treatment-related adverse events of any grade
    occurring in 10 percent or more of patients were nausea (36 percent),
    pruritus (31 percent), fatigue (30 percent) and diarrhea (28 percent).
    The most common Grade 3 or 4 adverse events occurring in five percent
    or more of patients, regardless of attribution, were urinary tract
    infections, hypophosphatemia, hyponatremia and anemia.
  • These results support further development of enfortumab vedotin as
    monotherapy and in combination with other therapies for patients with
    mUC. Enrollment is ongoing at the RP2D in patients with mUC who have
    been previously treated with CPIs.

More information about this clinical trial (NCT02091999), including
enrolling centers, is available by visiting

About Urothelial Cancer

Urothelial cancer is most commonly found in the bladder (90 percent).
According to the American Cancer Society, approximately 79,000 people in
the U.S. will be diagnosed with bladder cancer during 2017 and almost
17,000 will die from the disease. Outcomes are poor for patients
diagnosed with metastatic disease, with a five-year survival rate of
five percent.

About Enfortumab Vedotin

Enfortumab vedotin is an investigational ADC composed of an
anti-Nectin-4 monoclonal antibody attached to a microtubule-disrupting
agent, MMAE, using Seattle Genetics' proprietary, industry-leading
linker technology. Enfortumab vedotin is the first and only agent to
target Nectin-4, a cell adhesion molecule identified as an ADC target by
Agensys (an affiliate of Astellas), which is expressed on many solid

Nectin-4 is highly expressed in urothelial cancers, particularly in
bladder cancer. Preclinical data demonstrate that enfortumab vedotin
binds to Nectin-4 on cancer cells and releases the cell-killing agent
into these target cells upon internalization.

About Astellas

Astellas is a pharmaceutical company dedicated to improving the health
of people around the world through the provision of innovative and
reliable pharmaceutical products. For more information on Astellas,
please visit our website at
You can also follow us on Twitter at @AstellasUS,
Facebook at
or LinkedIn at

About Seattle Genetics

Seattle Genetics is an innovative biotechnology company that develops
and commercializes novel antibody-based therapies for the treatment of
cancer. The company's industry-leading antibody-drug conjugate (ADC)
technology harnesses the targeting ability of antibodies to deliver
cell-killing agents directly to cancer cells. ADCETRIS®
(brentuximab vedotin), the company's lead product, in collaboration with
Takeda Pharmaceutical Company Limited, is the first in a new class of
ADCs and is commercially available globally in 67 countries for relapsed
classical Hodgkin lymphoma (HL) and relapsed systemic anaplastic large
cell lymphoma (sALCL). Seattle Genetics is also advancing vadastuximab
talirine (SGN-CD33A; 33A), an ADC in a phase 3 trial for acute myeloid
leukemia and in collaboration with Astellas, enfortumab vedotin, an ADC
in a planned pivotal phase 2 trial for metastatic urothelial cancer.
Headquartered in Bothell, Washington, Seattle Genetics has a robust
pipeline of innovative therapies for blood-related cancers and solid
tumors designed to address significant unmet medical needs and improve
treatment outcomes for patients. The company has collaborations for its
proprietary ADC technology with a number of companies including AbbVie,
Astellas, Bayer, Celldex, Genentech, GlaxoSmithKline and Pfizer. More
information can be found at

About the Astellas and Seattle Genetics Collaboration

Agensys (an affiliate of Astellas) and Seattle Genetics entered into the
ADC collaboration in January 2007 and expanded it in November 2009.
Under the collaboration, the companies are co-developing and have
options to globally co-commercialize enfortumab vedotin.

Seattle Genetics Forward Looking Statement

Certain of the statements made in this press release are forward
looking, such as those, among others, relating to the therapeutic
potential of enfortumab vedotin, its possible safety, efficacy, and
therapeutic uses and anticipated development activities including future
clinical trials and intended regulatory actions. Actual results or
developments may differ materially from those projected or implied in
these forward-looking statements. Factors that may cause such a
difference include the inability to show sufficient activity in the
clinical trials and risk of adverse events as enfortumab vedotin advance
in clinical trials even after promising results in earlier clinical
trials. In addition, as our drug candidates or those of our
collaborators advance in clinical trials, adverse events and/or
regulatory actions may occur which affect the future development of
those drug candidates and possibly other compounds using similar
technology. More information about the risks and uncertainties faced by
Seattle Genetics is contained under the caption "Risk Factors" included
in the company's Quarterly Report on Form 10-Q for the quarter ended
March 31, 2017 filed with the Securities and Exchange Commission.
Seattle Genetics disclaims any intention or obligation to update or
revise any forward-looking statements, whether as a result of new
information, future events or otherwise.

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