Clovis Oncology’s Rucaparib Demonstrates Encouraging Results from Ongoing Phase I/II Monotherapy Study in Patients with Solid

  Clovis Oncology’s Rucaparib Demonstrates Encouraging Results from Ongoing
  Phase I/II Monotherapy Study in Patients with Solid Tumors

  *Objective responses seen in BRCA-mutant ovarian, breast and pancreatic
                                 cancer patients
    *89% clinical benefit rate in ovarian cancer patients across all doses
                  *Rucaparib well-tolerated at doses studied
        *Consistent therapeutic drug exposures observed with BID dosing
  *Phase II dose not yet defined; MTD not yet reached

2013 ASCO Annual Meeting

Business Wire

BOULDER, Colo. -- June 3, 2013

Clovis Oncology (NASDAQ:CLVS) today announced initial findings from an ongoing
Phase I/II monotherapy study of rucaparib, the Company’s oral, potent, small
molecule poly (ADP-ribose) polymerase (PARP) inhibitor being developed for the
treatment of ovarian cancer. Initial results from the Phase I dose-escalation
portion of this Phase I/II study are being presented for the first time today
at a poster session during the American Society of Clinical Oncology (ASCO)
Annual Meeting 2013 in Chicago.

“Oral rucaparib is a potent PARP inhibitor active in patients with ovarian,
breast and pancreatic cancers. Clinically meaningful results have been seen in
the rucaparib monotherapy Phase I trial; 89% of patients with ovarian cancer
demonstrated a clinical benefit. Increasing evidence suggests that genetic
analysis of ovarian tumors can help identify patients who derive benefit from
PARP inhibitor therapy – best known predictors are mutations in BRCA genes,
either at germline or somatic level, but there are likely other predictive
mutations as well. The Clovis development program seeks to exploit these new
insights and I am pleased to be jointly leading their larger-scale trials to
assess the full clinical potential of this well-tolerated drug in ovarian
cancer,” said Professor Jonathan Ledermann, Professor of Medical Oncology &
Director, Cancer Research UK and UCL Cancer Trials Centre, UCL Cancer
Institute.

“These initial results suggest that rucaparib is both well-tolerated and
predictably absorbed, and provides meaningful clinical benefit to certain
ovarian cancer patients,” said Patrick J. Mahaffy, President and CEO of Clovis
Oncology. “Once we identify the recommended Phase II dose, we look forward to
commencing the late-stage development program in platinum-sensitive ovarian
cancer in 2H13. This comprises two trials - a biomarker study which will
refine the definition of patients beyond those with mutant BRCA who may
benefit from rucaparib, and a Phase III pivotal trial in all patients with a
stratified efficacy analysis in genetically-defined groups, including somatic
and germline BRCA mutations as well as a broader population with mutations
beyond BRCA, utilizing insights from the biomarker study.”

The Phase I dose escalation portion of the study is open to patients with all
solid tumors. Study objectives were typical for a Phase I trial, including
determining safety and tolerability, evaluating the pharmacokinetic profile,
identifying the maximum tolerated dose (MTD) and recommended Phase II dose
(RP2D) as well as the preliminary efficacy signals in various solid tumors.

Thirty-seven patients have been treated with rucaparib monotherapy in this
study as of May 2013, in once-daily (QD) and twice-daily (BID) dosing cohorts,
up to 300 mg QD and 480 mg BID. Dose-escalation continues and the MTD has not
yet been reached.

Patients have received a median of four previous anticancer regimens and over
half have received three or more previous therapies. Twenty-one patients (57%)
have breast tumors, 10 patients (27%) have ovarian/peritoneal tumors and six
patients (16%) have other solid tumors.

Key data from the study presented at ASCO include:

Evidence of Activity

Objective responses have been observed in ovarian, breast and pancreatic
cancer patients with germline BRCA mutations. Durable disease control has been
observed in heavily pre-treated ovarian cancer patients across all dose
levels, with a disease control rate of 89% (stable disease or better beyond 12
weeks after study initiation in 8 of 9 ovarian cancer patients). The disease
control rate for germline BRCA mutant ovarian cancer patients was 100% (7 of
7). Measurable disease was not a requirement for entry into the dose
escalation phase of the study, precluding systematic response analysis.

Safety and Tolerability

Safety data to date shows rucaparib to be well-tolerated, which is important
for a drug intended to be used in a maintenance setting. There were 19
patients (54%) with treatment-related adverse events. The most common adverse
events attributed to rucaparib therapy include fatigue (23%), nausea (14%) and
decreased appetite (11%). No patient experienced a treatment-related adverse
event that led to study drug discontinuation and no grade 3/4 myelosuppression
has been observed in any patient. There have been two treatment related grade
3 toxicities: one patient with grade 3 nausea and one patient with grade 3
fatigue.

Pharmacokinetics

Oral rucaparib has attractive pharmacokinetic properties as a potential oral
cancer therapeutic. Patients receiving BID doses above 240 mg experienced
consistently high plasma drug concentrations throughout the 24-hour period,
which is likely important for optimal activity. Intra- and inter-patient
variability was also low, which is advantageous for uniform flat dosing
strategies.

The poster, titled “A Phase I Dose Escalation and Pharmacokinetic Study of
Continuous Oral Rucaparib in Patients with Advanced Solid Tumors,” is being
presented on Monday, June 3, 8:00am – 11:45am CDT, in S Hall A2, Poster Board:
7E at McCormick Place in Chicago. The poster will also be available at
www.clovisoncology.com.

About Rucaparib

Rucaparib is an oral, potent inhibitor of PARP1 and PARP2 in development for
the treatment of ovarian cancer. Rucaparib is currently in two
Company-sponsored Phase I clinical studies; one to determine the maximum
tolerated dose (MTD) of oral rucaparib administered on a daily basis as
monotherapy; and a second trial to determine the MTD of oral rucaparib that
can be combined with intravenous platinum chemotherapy for the treatment of
solid tumors. Once the optimal dose and schedule have been established in the
Phase I portion of the monotherapy study, the Company will initiate a Phase II
expansion cohort to assess efficacy in selected ovarian cancer patients. The
Company expects to initiate a biomarker study in platinum-sensitive ovarian
cancer patients in the third quarter of 2013, as well as the pivotal Phase III
study in platinum-sensitive ovarian cancer patients in late 2013.

About Clovis Oncology

Clovis Oncology, Inc. is a biopharmaceutical company focused on acquiring,
developing and commercializing innovative anti-cancer agents in the U.S.,
Europe and additional international markets. Clovis Oncology targets
development programs at specific subsets of cancer populations, and
simultaneously develops diagnostic tools that direct a compound in development
to the population that is most likely to benefit from its use. Clovis Oncology
is headquartered in Boulder, Colorado, and has additional offices in San
Francisco, California and Cambridge, UK.

To the extent that statements contained in this press release are not
descriptions of historical facts regarding Clovis Oncology, they are
forward-looking statements reflecting the current beliefs and expectations of
management made pursuant to the safe harbor provisions of the Private
Securities Litigation Reform Act of 1995. Such forward-looking statements
involve substantial risks and uncertainties that could cause our clinical
development programs, future results, performance or achievements to differ
significantly from those expressed or implied by the forward-looking
statements. Such risks and uncertainties include, among others, the
uncertainties inherent in the initiation of future clinical trials,
availability of data from ongoing clinical trials, expectations for regulatory
approvals, and other matters that could affect the availability or commercial
potential of our drug candidates. Clovis Oncology undertakes no obligation to
update or revise any forward-looking statements. For a further description of
the risks and uncertainties that could cause actual results to differ from
those expressed in these forward-looking statements, as well as risks relating
to the business of the company in general, see Clovis Oncology’s Annual Report
on Form 10-K for the year ended December31, 2012 and its other reports filed
with the Securities and Exchange Commission.

Contact:

Clovis Oncology
Anna Sussman, 303-625-5022
asussman@clovisoncology.com
or
Breanna Burkart, 303-625-5023
bburkart@clovisoncology.com
 
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