– 54 percent objective response rate and 43 percent stable disease

observed among 35 evaluable patients –

– Exelixis plans to initiate a pivotal phase 3 trial later this

year –

– Results to be presented during an oral session on February 16 at

the 2018 Multidisciplinary Head and Neck Cancers Symposium –

SOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)--Exelixis,

Inc. (NASDAQ:EXEL) today announced results from a phase 2

investigator-sponsored trial (IST) of cabozantinib for the first-line

treatment of metastatic radioiodine (RAI)-refractory differentiated

thyroid carcinoma (DTC). The results were the subject of a news briefing

that took place earlier today and will be presented during an oral

session on February 16 starting at 1:30 p.m. MT at the 2018

Multidisciplinary Head and Neck Cancers Symposium, which is being held

in Scottsdale, Arizona, February 15–17, 2018.

Patients with metastatic, RAI-refractory DTC were enrolled in this

single-arm, open-label trial, and were administered oral cabozantinib 60

mg once daily. The primary endpoint of the trial is objective response

rate. Among the 35 patients who were evaluable for response, partial

response was achieved by 54 percent of patients (n=19), and stable

disease was reported in 43 percent of patients (n=15) per RECIST 1.1.

All but one evaluated patient experienced a decrease in tumor target

lesions. Secondary endpoints of the trial include progression-free

survival (PFS), time to progression (TTP), duration of response (DOR)

and clinical benefit rate (CBR) defined as the number of patients

achieving an objective response or stable disease for at least 6 months.

The CBR at six months was 80 percent (n=28). With a median follow up for

the study of 35 weeks the median PFS has not been reached. The median

TTP among those patients who progressed was 35 weeks.

“While many patients with differentiated thyroid cancer can be treated

successfully with radioiodine, there are very few options for those

patients whose tumors have become resistant to treatment,” said Marcia

Brose, M.D., Ph.D., Associate Professor of Otorhinolaryngology: Head and

Neck Surgery and Director of the Center for Rare Cancers at the Abramson

Cancer Center of the University of Pennsylvania, and principal

investigator of the trial. “These findings suggest that cabozantinib,

which showed encouraging efficacy and a manageable safety profile in

this phase 2 trial, may be a promising treatment option for this patient

population and warrants further evaluation.”

“We are dedicated to supporting investigator-sponsored trials focused on

evaluating cabozantinib in a range of tumor types to help inform our

ongoing development program whose main goal is to provide improved

treatment options to patients in need,” said Gisela Schwab, M.D.,

President, Product Development and Medical Affairs and Chief Medical

Officer, Exelixis. “Based on these promising results and data from other

studies of cabozantinib in previously treated DTC, Exelixis plans to

initiate a pivotal phase 3 study with cabozantinib in patients with

advanced DTC later this year.”

The most common treatment-related adverse events included hyperglycemia

(80 percent), diarrhea (77 percent), malaise/fatigue (74 percent), and

weight loss (71 percent). The majority of these adverse events were

grade 1 or 2. The most comment grade 3-5 adverse events occurring in

more than one patient included hypertension (14 percent), increased

lipase (9 percent), pulmonary embolism (6 percent), and hyponatremia (6

percent).

About the Trial

The IST is being conducted by the Center for Rare Cancers and

Personalized Therapy at the Abramson Cancer Center of the University of

Pennsylvania. Enrollment for the trial was completed in August 2017. Dr.

Marcia Brose, Associate Professor of Otorhinolaryngology: Head and Neck

Surgery, Perelman School of Medicine of the University of Pennsylvania

is the principal investigator. The median age of patients is 65 years

(range 45 to 84) and 17 patients (49 percent) are male. Of the patients

in the trial, 23 (66 percent) had papillary thyroid cancer, 3 (9

percent) had follicular (Hürthle cell) thyroid cancer and 9 (26 percent)

had poorly differentiated histology. Patients are administered oral

cabozantinib 60 mg once daily as long as they continue to derive

clinical benefit or until unacceptable drug-related toxicity. Sixteen

patients remain on the trial as of February 6, 2018.

About Differentiated Thyroid Carcinoma

Thyroid cancer is commonly diagnosed at a younger age than most other

adult cancers and is the most rapidly increasing cancer in the U.S.,

tripling in incidence in the past three decades.1

Approximately 54,000 new cases of thyroid cancer will be diagnosed in

the U.S. in 2018.1 Nearly three out of four of these cases

will be in women.1 Cancerous thyroid tumors include

differentiated, medullary and anaplastic forms.1

Differentiated thyroid tumors, which make up about 90 percent of all

thyroid cancers, are typically treated with surgery followed by ablation

of the remaining thyroid with radioiodine.2 Approximately 5

to 15 percent of differentiated thyroid tumors are resistant to

radioiodine treatment.3 For these patients, life expectancy

is only three to six years from the time metastatic lesions are detected.4-6

About CABOMETYX® (cabozantinib)

CABOMETYX tablets are approved in the United States for the treatment of

patients with advanced RCC. CABOMETYX tablets are also approved in the

European Union, Norway, Iceland, Australia and Switzerland for the

treatment of advanced RCC in adults who have received prior vascular

endothelial growth factor (VEGF)-targeted therapy. Ipsen also submitted

to European Medicines Agency (EMA) the regulatory dossier for

cabozantinib as a treatment for first-line advanced RCC in the European

Union on August 28, 2017; on September 8, 2017, Ipsen announced that the

EMA validated the application. In 2016, Exelixis granted Ipsen exclusive

rights for the commercialization and further clinical development of

cabozantinib outside of the United States and Japan. In 2017, Exelixis

granted exclusive rights to Takeda Pharmaceutical Company Limited for

the commercialization and further clinical development of cabozantinib

for all future indications in Japan, including RCC.

CABOMETYX is not indicated for the treatment of differentiated thyroid

carcinoma.

Please see Important Safety Information below and full U.S. prescribing

U.S. Important Safety Information



  • Hemorrhage: Severe and fatal hemorrhages have occurred with
    CABOMETYX. In two RCC studies, the incidence of Grade ≥ 3 hemorrhagic
    events was 3% in CABOMETYX-treated patients. Do not administer
    CABOMETYX to patients that have or are at risk for severe hemorrhage.


  • Gastrointestinal (GI) Perforations and Fistulas: In RCC
    studies, fistulas were reported in 1% of CABOMETYX-treated patients.
    Fatal perforations occurred in patients treated with CABOMETYX. In RCC
    studies, gastrointestinal (GI) perforations were reported in 1% of
    CABOMETYX-treated patients. Monitor patients for symptoms of fistulas
    and perforations, including abscess and sepsis. Discontinue CABOMETYX
    in patients who experience a fistula which cannot be appropriately
    managed or a GI perforation.


  • Thrombotic Events: CABOMETYX treatment results in an increased
    incidence of thrombotic events. In RCC studies, venous thromboembolism
    occurred in 9% (including 5% pulmonary embolism) and arterial
    thromboembolism occurred in 1% of CABOMETYX-treated patients. Fatal
    thrombotic events occurred in the cabozantinib clinical program.
    Discontinue CABOMETYX in patients who develop an acute myocardial
    infarction or any other arterial thromboembolic complication.


  • Hypertension and Hypertensive Crisis: CABOMETYX treatment
    results in an increased incidence of treatment-emergent hypertension,
    including hypertensive crisis. In RCC studies, hypertension was
    reported in 44% (18% Grade ≥ 3) of CABOMETYX-treated patients. Monitor
    blood pressure prior to initiation and regularly during CABOMETYX
    treatment. Withhold CABOMETYX for hypertension that is not adequately
    controlled with medical management; when controlled, resume CABOMETYX
    at a reduced dose. Discontinue CABOMETYX for severe hypertension that
    cannot be controlled with anti-hypertensive therapy. Discontinue
    CABOMETYX if there is evidence of hypertensive crisis or severe
    hypertension despite optimal medical management.


  • Diarrhea: In RCC studies, diarrhea occurred in 74% of patients
    treated with CABOMETYX. Grade 3 diarrhea occurred in 11% of patients
    treated with CABOMETYX. Withhold CABOMETYX in patients who develop
    intolerable Grade 2 diarrhea or Grade 3-4 diarrhea that cannot be
    managed with standard antidiarrheal treatments until improvement to
    Grade 1; resume CABOMETYX at a reduced dose.


  • Palmar-Plantar Erythrodysesthesia (PPE): In RCC studies,
    palmar-plantar erythrodysesthesia (PPE) occurred in 42% of patients
    treated with CABOMETYX. Grade 3 PPE occurred in 8% of patients treated
    with CABOMETYX. Withhold CABOMETYX in patients who develop intolerable
    Grade 2 PPE or Grade 3 PPE until improvement to Grade 1; resume
    CABOMETYX at a reduced dose.


  • Reversible Posterior Leukoencephalopathy Syndrome (RPLS), a
    syndrome of subcortical vasogenic edema diagnosed by characteristic
    finding on MRI, occurred in the cabozantinib clinical program. Perform
    an evaluation for RPLS in any patient presenting with seizures,
    headache, visual disturbances, confusion or altered mental function.
    Discontinue CABOMETYX in patients who develop RPLS.


  • Embryo-fetal Toxicity may be associated with CABOMETYX. Advise
    pregnant women of the potential risk to a fetus. Advise females of
    reproductive potential to use effective contraception during CABOMETYX
    treatment and for 4 months after the last dose.


  • Adverse Reactions: The most commonly reported (≥25%) adverse
    reactions are: diarrhea, fatigue, nausea, decreased appetite,
    hypertension, PPE, weight decreased, vomiting, dysgeusia, and
    stomatitis.


  • Strong CYP3A4 Inhibitors: If concomitant use with strong CYP3A4
    inhibitors cannot be avoided, reduce the CABOMETYX dosage.


  • Strong CYP3A4 Inducers: If concomitant use with strong CYP3A4
    inducers cannot be avoided, increase the CABOMETYX dosage.


  • Lactation: Advise women not to breastfeed while taking
    CABOMETYX and for 4 months after the final dose.


  • Hepatic Impairment: In patients with mild to moderate hepatic
    impairment, reduce the CABOMETYX dosage. CABOMETYX is not
    recommended for use in patients with severe hepatic impairment.

Please see accompanying full Prescribing Information https://cabometyx.com/downloads/cabometyxuspi.pdf.

About Exelixis

Founded in 1994, Exelixis, Inc. (NASDAQ: EXEL) is a commercially

successful, oncology-focused biotechnology company that strives to

accelerate the discovery, development and commercialization of new

medicines for difficult-to-treat cancers. Following early work in model

genetic systems, we established a broad drug discovery and development

platform that has served as the foundation for our continued efforts to

bring new cancer therapies to patients in need. We discovered our lead

compounds, cabozantinib and cobimetinib, and advanced them into clinical

development before entering into partnerships with leading

biopharmaceutical companies in our efforts to bring these medicines to

patients globally. We are steadfast in our commitment to prudently

reinvest in our business to maximize the potential of our pipeline. We

intend to supplement our existing therapeutic assets with targeted

business development activities and internal drug discovery – all to

deliver the next generation of Exelixis medicines and help patients

recover stronger and live longer. Exelixis recently earned a spot on

Deloitte’s Technology Fast 500 list, a yearly award program honoring the

500 fastest-growing companies over the past four years. For more

information about Exelixis, please visit www.exelixis.com

or follow @ExelixisInc on Twitter.

Exelixis Forward-Looking Statement Disclaimer

This press release contains forward-looking statements, including,

without limitation, statements related to: Exelixis’ plans to initiate a

pivotal phase 3 trial with cabozantinib in patients with advanced DTC

later this year; the future presentation of data results from a phase 2

IST of cabozantinib for the first-line treatment of metastatic

radioiodine (RAI)-refractory DTC at the 2018 Multidisciplinary Head and

Neck Cancers Symposium; the clinical and therapeutic potential of

cabozantinib for patients with DTC; Exelixis’ continued support of ISTs

focused on evaluating cabozantinib in a range of tumor types; Exelixis’

goal to provide improved treatment options to patients in need; and

Exelixis’ commitment to reinvesting in its business to maximize the

potential of its pipeline, including supplementing its existing

therapeutic assets through targeted business development activities and

internal drug discovery. Words such as “plan,” “will,” “may,” “focused,”

“goal,” “potential,” “future,” “commitment,” “intend,” or other similar

expressions identify forward-looking statements, but the absence of

these words does not necessarily mean that a statement is not

forward-looking. In addition, any statements that refer to expectations,

projections or other characterizations of future events or circumstances

are forward-looking statements. These forward-looking statements are

based upon Exelixis’ current plans, assumptions, beliefs, expectations,

estimates and projections. Forward-looking statements involve risks and

uncertainties. Actual results and the timing of events could differ

materially from those anticipated in the forward-looking statements as a

result of these risks and uncertainties, which include, without

limitation: the potential failure of cabozantinib to demonstrate safety

and efficacy in clinical testing; the availability of data at the

referenced times; Exelixis’ ability and the ability of its collaborators

to conduct clinical trials of cabozantinib sufficient to achieve a

positive completion; the complexities and challenges associated with

regulatory review and approval processes; the level of costs associated

with Exelixis’ commercialization, research and development and other

activities; competition in the area of business development activities

and the inherent uncertainty of the drug discovery process; Exelixis’

dependence on its relationships with its cabozantinib collaboration

partners, including, the level of their investment in the resources

necessary to successfully commercialize cabozantinib in the territories

where it is approved; Exelixis’ dependence on its relationship with

Genentech/Roche with respect to cobimetinib and Exelixis’ ability to

maintain its rights under the collaboration; market acceptance of

CABOMETYX, COMETRIQ, and COTELLIC and the availability of coverage and

reimbursement for these products; Exelixis’ dependence on third-party

vendors for the development, manufacture and supply of its products;

Exelixis’ ability to protect the company’s intellectual property rights;

market competition; changes in economic and business conditions, and

other factors discussed under the caption “Risk Factors” in Exelixis’

quarterly report on Form 10-Q filed with the Securities and Exchange

Commission (SEC) on November 1, 2017, and in Exelixis’ future filings

with the SEC. The forward-looking statements made in this press release

speak only as of the date of this press release. Exelixis expressly

disclaims any duty, obligation or undertaking to release publicly any

updates or revisions to any forward-looking statements contained herein

to reflect any change in Exelixis’ expectations with regard thereto or

any change in events, conditions or circumstances on which any such

statements are based.

Exelixis, the Exelixis logo, CABOMETYX, COMETRIQ and COTELLIC are

registered U.S. trademarks.

References:



  1. American Cancer Society. Key Statistics for Thyroid Cancer. https://www.cancer.org/cancer/thyroid-cancer/about/key-statistics.html.
    Accessed January 2018.


  2. Cooper DS, et al. 2009. Revised American Thyroid Association
    management guidelines for patients with thyroid nodules and
    differentiated thyroid cancer: the American Thyroid Association (ATA)
    Guidelines Taskforce on Thyroid Nodules and Differentiated Thyroid
    Cancer. Thyroid 19:1167–1214.


  3. Worden F. 2014. Treatment strategies for radioactive iodine-refractory
    differentiated thyroid cancer. Ther Adv Med Oncol 6:267–279.


  4. Xing M, Haugen BR, Schlumberger M. 2013. Progress in molecular-based
    management of differentiated thyroid cancer. Lancet
    381:1058–1069.


  5. Pacini F, et al. 2012. Radioactive iodine-refractory differentiated
    thyroid cancer: unmet needs and future directions. Expert Rev
    Endocrinol Metab
    7:541–554.


  6. Durante C, et al. 2006. Long-term outcome of 444 patients with distant
    metastases from papillary and follicular thyroid carcinoma: benefits
    and limits of radioiodine therapy. J Clin Endocrinol Metab
    91:2892–2899.

Contacts

Exelixis, Inc.

Investors:

Susan Hubbard,

650-837-8194

EVP, Public Affairs and Investor Relations

or

Media:

Lindsay

Treadway, 650-837-7522

Director, Public Affairs and Advocacy

Relations