Arvinas, Inc. (Nasdaq: ARVN) and Pfizer Inc. (NYSE: PFE) today
announced a global collaboration to develop and commercialize
ARV-471, an investigational oral PROTAC® (PROteolysis TArgeting
Chimera) estrogen receptor protein degrader. The estrogen receptor
is a well-known disease driver in most breast cancers. ARV-471 is
currently in a Phase 2 dose expansion clinical trial for the
treatment of patients with estrogen receptor (ER) positive / human
epidermal growth factor receptor 2 (HER2) negative (ER+/HER2-)
locally advanced or metastatic breast cancer. Under the terms of
the agreement, Pfizer will pay Arvinas $650 million upfront.
Separately, Pfizer will make a $350 million equity investment in
Arvinas. The companies will equally share worldwide development
costs, commercialization expenses, and profits.
“This collaboration has the potential to be transformational, as
it combines our leadership in targeted protein degradation with
Pfizer’s global capabilities and deep expertise in breast cancer.
This should significantly enhance and accelerate the development
and potential commercialization of ARV-471 while also advancing
Arvinas’ strategy of building a global, integrated
biopharmaceutical company,” said John Houston, Ph.D., Chief
Executive Officer at Arvinas. “We share Pfizer’s deep commitment to
people with breast cancer and are thrilled to partner with them to
develop this potentially best-in-class therapy. Despite
advancements in oncology in recent years, considerable unmet need
persists in the treatment of HR+ breast cancer. Together with
Pfizer, we will deploy our PROTAC technology in an effort to help
people with this devastating disease.”
“Building on Pfizer’s established leadership position in breast
cancer science and CDK 4/6 inhibition, we are excited to work with
Arvinas to maximize ARV-471, the first PROTAC for breast cancer
with encouraging early clinical data and a potential novel hormonal
therapy backbone for HR+ breast cancer,” said Jeff Settleman,
Ph.D., Chief Scientific Officer for Oncology Research and
Development at Pfizer. “This partnership complements Pfizer’s
robust research activities in breast cancer, including our multiple
next-generation CDK inhibitors currently in early clinical
development.”
ER is the primary driver of hormone receptor (HR) positive
breast cancer, which is the most common breast cancer subtype.
Endocrine therapy is a backbone of ER+ breast cancer treatment and
is used as monotherapy or as combination therapy as a standard of
care across treatment settings. Arvinas and Pfizer are seeking to
develop ARV-471 as the potential endocrine therapy of choice for
patients and their physicians.
Interim data presented in December 2020 from the ongoing Phase 1
dose escalation clinical trial of ARV-471 in patients with locally
advanced or metastatic ER+/HER2- breast cancer indicated its
potential as a novel oral ER targeted therapy. This study has
enrolled heavily pretreated patients, with all patients having
received prior treatment with cyclin-dependent kinase (CDK) 4/6
inhibitors. Despite the advanced stage of disease and heavy
pretreatment, these interim data, as of December 2020, demonstrated
that ARV-471 can promote substantial ER degradation and exhibits an
encouraging clinical efficacy and tolerability profile.
ARV-471 currently is being evaluated as a treatment for
metastatic breast cancer in a Phase 1 dose escalation study, a
Phase 1b combination study with Pfizer’s IBRANCE® (palbociclib),
and a Phase 2 monotherapy dose expansion study (VERITAC). Arvinas
and Pfizer expect to initiate two additional trials of ARV-471 in
2021, including a second Phase 1b combination trial with everolimus
and a trial in the neoadjuvant setting. In 2022, Arvinas and Pfizer
expect to initiate Phase 3 studies across lines of therapy in
metastatic breast cancer, including combinations with IBRANCE,
followed by pivotal studies in the early breast cancer setting. The
two companies had previously announced in 2018 a separate research
collaboration and license agreement for the discovery and
development of drug candidates using Arvinas’ PROTAC
technology.
Terms of the Collaboration
The agreement is a worldwide co-development and
co-commercialization collaboration. ARV-471 is wholly owned by
Arvinas and under the financial terms of the agreement, Pfizer will
pay Arvinas $650 million upfront. Separately, Pfizer will invest
$350 million in Arvinas, receiving approximately 3.5 million newly
issued shares of Arvinas common stock, priced at a 30% premium to
the 30-day volume weighted average price on July 20, 2021. This
represents an equity ownership stake by Pfizer of approximately
7%.
Arvinas is also eligible to receive up to $400 million in
approval milestones and up to $1 billion in commercial milestones,
in addition to sharing profits on ARV-471 worldwide.
Arvinas and Pfizer will jointly develop ARV-471 through a robust
clinical program designed to position ARV-471 as an endocrine
backbone therapy of choice across the breast cancer treatment
paradigm, from the adjuvant setting through late-line metastatic
disease.
Closing of the equity investment agreement is contingent on
completion of review under antitrust laws, including the
Hart-Scott-Rodino (HSR) Antitrust Improvements Act of 1976 in the
U.S., and other customary closing conditions.
Goldman Sachs & Co. LLC is acting as the exclusive financial
advisor to Arvinas.
Investor Conference Call Details
A conference call and webcast will be held at 8:30 AM ET today
with Arvinas and Pfizer Oncology executives to discuss the
collaboration. Participants are invited to listen by dialing (844)
467-7654 (domestic) or (602) 563-8497 (international) five minutes
prior to the start of the call and providing the passcode
6569429.
Supporting materials for the conference call and webcast will be
available here or on the Company’s website at www.arvinas.com under
Events + Presentations. A replay of the webcast will be archived on
the Arvinas website following the presentation.
About ArvinasArvinas is a clinical-stage
biopharmaceutical company dedicated to improving the lives of
patients suffering from debilitating and life-threatening diseases
through the discovery, development, and commercialization of
therapies that degrade disease-causing proteins. Arvinas uses its
proprietary PROTAC® Discovery Engine platform to engineer
proteolysis targeting chimeras, or PROTAC® targeted protein
degraders, that are designed to harness the body’s own natural
protein disposal system to selectively and efficiently degrade and
remove disease-causing proteins. In addition to its robust
preclinical pipeline of PROTAC® protein degraders against validated
and “undruggable” targets, the company has two clinical-stage
programs: ARV-110 for the treatment of men with metastatic
castrate-resistant prostate cancer; and ARV-471 for the treatment
of patients with locally advanced or metastatic ER+/HER2- breast
cancer. For more information, visit www.arvinas.com.
Arvinas Forward-Looking StatementsThis press
release contains forward-looking statements that involve
substantial risks and uncertainties, including statements regarding
the closing of the collaboration with Pfizer, the receipt of
upfront, milestone and other payments under the Pfizer
collaboration, the investment by Pfizer in Arvinas common stock in
connection with the collaboration, the future development and
potential marketing approval and commercialization of ARV-471, the
potential benefits of the collaboration and the potential
advantages and therapeutic benefits of ARV-471 and our other
product candidates. All statements, other than statements of
historical facts, contained in this press release, including
statements regarding our strategy, future operations, prospects,
plans and objectives of management, are forward-looking statements.
The words “anticipate,” “believe,” “estimate,” “expect,” “intend,”
“may,” “might,” “plan,” “predict,” “project,” “target,”
“potential,” “will,” “would,” “could,” “should,” “continue,” and
similar expressions are intended to identify forward-looking
statements, although not all forward-looking statements contain
these identifying words.
We may not actually achieve the plans, intentions or
expectations disclosed in our forward-looking statements, and you
should not place undue reliance on our forward-looking statements.
Actual results or events could differ materially from the plans,
intentions and expectations disclosed in the forward-looking
statements we make as a result of various risks and uncertainties,
including but not limited to: the satisfaction or waiver of the
conditions to the closing of the Pfizer collaboration and equity
investment, each party’s performance of its obligations under the
collaboration, whether we and Pfizer will be able to successfully
conduct and complete clinical development, obtain marketing
approval for and commercialize ARV-471 on our current timelines or
at all and other important factors discussed in the “Risk Factors”
sections contained in our quarterly and annual reports on file with
the Securities and Exchange Commission. The forward-looking
statements contained in this press release reflect our current
views with respect to future events, and we assume no obligation to
update any forward-looking statements except as required by
applicable law. These forward-looking statements should not be
relied upon as representing our views as of any date subsequent to
the date of this release.
About IBRANCE® (palbociclib) 125 mg tablets and
capsules
IBRANCE is an oral inhibitor of CDKs 4 and 6,1 which are key
regulators of the cell cycle that trigger cellular progression.2,3
In the U.S., IBRANCE is indicated for the treatment of adult
patients with HR+, HER2- advanced or metastatic breast cancer in
combination with an aromatase inhibitor as initial endocrine based
therapy in postmenopausal women or in men; or with fulvestrant in
patients with disease progression following endocrine therapy.
The full U.S. Prescribing Information for the IBRANCE tablets
and the IBRANCE capsules can be found here and here.
IMPORTANT IBRANCE®
(palbociclib) SAFETY INFORMATION FROM THE U.S. PRESCRIBING
INFORMATION
Neutropenia was the most frequently reported
adverse reaction in PALOMA-2 (80%) and PALOMA-3 (83%). In PALOMA-2,
Grade 3 (56%) or 4 (10%) decreased neutrophil counts were reported
in patients receiving IBRANCE plus letrozole. In PALOMA-3, Grade 3
(55%) or Grade 4 (11%) decreased neutrophil counts were reported in
patients receiving IBRANCE plus fulvestrant. Febrile neutropenia
has been reported in 1.8% of patients exposed to IBRANCE across
PALOMA-2 and PALOMA-3. One death due to neutropenic sepsis was
observed in PALOMA-3. Inform patients to promptly report any
fever.
Monitor complete blood count prior to starting IBRANCE, at the
beginning of each cycle, on Day 15 of first 2 cycles and as
clinically indicated. Dose interruption, dose reduction, or delay
in starting treatment cycles is recommended for patients who
develop Grade 3 or 4 neutropenia.
Severe, life-threatening, or fatal interstitial lung
disease (ILD) and/or pneumonitis can occur in patients
treated with CDK4/6 inhibitors, including IBRANCE when taken in
combination with endocrine therapy. Across clinical trials
(PALOMA-1, PALOMA-2, PALOMA-3), 1.0% of IBRANCE-treated patients
had ILD/pneumonitis of any grade, 0.1% had Grade 3 or 4, and no
fatal cases were reported. Additional cases of ILD/pneumonitis have
been observed in the post-marketing setting, with fatalities
reported.
Monitor patients for pulmonary symptoms indicative of
ILD/pneumonitis (e.g. hypoxia, cough, dyspnea). In patients who
have new or worsening respiratory symptoms and are suspected to
have developed pneumonitis, interrupt IBRANCE immediately and
evaluate the patient. Permanently discontinue IBRANCE in patients
with severe ILD or pneumonitis.
Based on the mechanism of action, IBRANCE can cause
fetal harm. Advise females of reproductive
potential to use effective contraception during IBRANCE treatment
and for at least 3 weeks after the last dose. IBRANCE may
impair fertility in males and has the potential to
cause genotoxicity. Advise male patients to consider sperm
preservation before taking IBRANCE. Advise male patients with
female partners of reproductive potential to use effective
contraception during IBRANCE treatment and for 3 months after the
last dose. Advise females to inform their healthcare provider of a
known or suspected pregnancy. Advise women not to
breastfeed during IBRANCE treatment and for 3 weeks after
the last dose because of the potential for serious adverse
reactions in nursing infants.
The most common adverse reactions
(≥10%) of any grade reported in
PALOMA-2 for IBRANCE plus letrozole vs placebo
plus letrozole were neutropenia (80% vs 6%), infections (60% vs
42%), leukopenia (39% vs 2%), fatigue (37% vs 28%), nausea (35% vs
26%), alopecia (33% vs 16%), stomatitis (30% vs 14%), diarrhea (26%
vs 19%), anemia (24% vs 9%), rash (18% vs 12%), asthenia (17% vs
12%), thrombocytopenia (16% vs 1%), vomiting (16% vs 17%),
decreased appetite (15% vs 9%), dry skin (12% vs 6%), pyrexia (12%
vs 9%), and dysgeusia (10% vs 5%).
The most frequently reported Grade ≥3 adverse reactions
(≥5%) in PALOMA-2 for IBRANCE plus
letrozole vs placebo plus letrozole were neutropenia (66% vs 2%),
leukopenia (25% vs 0%), infections (7% vs 3%), and anemia (5% vs
2%).
Lab abnormalities of any grade occurring in
PALOMA-2 for IBRANCE plus letrozole vs placebo
plus letrozole were decreased WBC (97% vs 25%), decreased
neutrophils (95% vs 20%), anemia (78% vs 42%), decreased platelets
(63% vs 14%), increased aspartate aminotransferase (52% vs 34%),
and increased alanine aminotransferase (43% vs 30%).
The most common adverse reactions (≥10%) of any
grade reported in PALOMA-3 for IBRANCE plus
fulvestrant vs placebo plus fulvestrant were neutropenia (83% vs
4%), leukopenia (53% vs 5%), infections (47% vs 31%), fatigue (41%
vs 29%), nausea (34% vs 28%), anemia (30% vs 13%), stomatitis (28%
vs 13%), diarrhea (24% vs 19%), thrombocytopenia (23% vs 0%),
vomiting (19% vs 15%), alopecia (18% vs 6%), rash (17% vs 6%),
decreased appetite (16% vs 8%), and pyrexia (13% vs 5%).
The most frequently reported Grade ≥3 adverse reactions
(≥5%) in PALOMA-3 for IBRANCE plus
fulvestrant vs placebo plus fulvestrant were neutropenia (66% vs
1%) and leukopenia (31% vs 2%).
Lab abnormalities of any grade occurring in
PALOMA-3 for IBRANCE plus fulvestrant vs placebo
plus fulvestrant were decreased WBC (99% vs 26%), decreased
neutrophils (96% vs 14%), anemia (78% vs 40%), decreased platelets
(62% vs 10%), increased aspartate aminotransferase (43% vs 48%),
and increased alanine aminotransferase (36% vs 34%).
Avoid concurrent use of strong CYP3A
inhibitors. If patients must be administered a strong
CYP3A inhibitor, reduce the IBRANCE dose to 75 mg. If the strong
inhibitor is discontinued, increase the IBRANCE dose (after 3-5
half-lives of the inhibitor) to the dose used prior to the
initiation of the strong CYP3A inhibitor. Grapefruit or grapefruit
juice may increase plasma concentrations of IBRANCE and should be
avoided. Avoid concomitant use of strong CYP3A
inducers. The dose of sensitive CYP3A
substrates with a narrow therapeutic index may need to be
reduced as IBRANCE may increase their exposure.
For patients with severe hepatic impairment
(Child-Pugh class C), the recommended dose of IBRANCE is 75 mg. The
pharmacokinetics of IBRANCE have not been studied
in patients requiring hemodialysis.
About Pfizer OncologyAt Pfizer Oncology, we are
committed to advancing medicines wherever we believe we can make a
meaningful difference in the lives of people living with cancer.
Today, we have an industry-leading portfolio of 24 approved
innovative cancer medicines and biosimilars across more than 30
indications, including breast, genitourinary, colorectal, blood and
lung cancers, as well as melanoma.
About Pfizer: Breakthroughs That Change Patients’
LivesAt Pfizer, we apply science and our global resources
to bring therapies to people that extend and significantly improve
their lives. We strive to set the standard for quality, safety and
value in the discovery, development and manufacture of health care
products, including innovative medicines and vaccines. Every day,
Pfizer colleagues work across developed and emerging markets to
advance wellness, prevention, treatments and cures that challenge
the most feared diseases of our time. Consistent with our
responsibility as one of the world's premier innovative
biopharmaceutical companies, we collaborate with health care
providers, governments and local communities to support and expand
access to reliable, affordable health care around the world. For
more than 170 years, we have worked to make a difference for all
who rely on us. We routinely post information that may be important
to investors on our website at www.Pfizer.com. In addition, to
learn more, please visit us on www.Pfizer.com and follow us on
Twitter at @Pfizer and @Pfizer News, LinkedIn, YouTube and like us
on Facebook at Facebook.com/Pfizer.
Pfizer Forward-Looking StatementsThe
information contained in this release is as of July 22, 2021.
Pfizer assumes no obligation to update forward-looking statements
contained in this release as the result of new information or
future events or developments.
This release contains forward-looking information about ARV-471
and a global collaboration between Pfizer and Arvinas to develop
and commercialize ARV-471, including their potential benefits, that
involves substantial risks and uncertainties that could cause
actual results to differ materially from those expressed or implied
by such statements. Risks and uncertainties include, among other
things, the uncertainties inherent in research and development,
including the ability to meet anticipated clinical endpoints,
commencement and/or completion dates for clinical trials,
regulatory submission dates, regulatory approval dates and/or
launch dates, as well as the possibility of unfavorable new
clinical data and further analyses of existing clinical data; the
risk that clinical trial data are subject to differing
interpretations and assessments by regulatory authorities; whether
regulatory authorities will be satisfied with the design of and
results from the clinical studies; whether and when any
applications may be filed for ARV-471 for any potential indications
in any jurisdictions; whether and when regulatory authorities may
approve any potential applications that may be filed for ARV-471 in
any jurisdictions, which will depend on myriad factors, including
making a determination as to whether the product’s benefits
outweigh its known risks and determination of the product’s
efficacy and, if approved, whether ARV-471 will be commercially
successful; decisions by regulatory authorities impacting labeling,
manufacturing processes, safety and/or other matters that could
affect the availability or commercial potential of ARV-471; risks
related to the satisfaction or waiver of the conditions to closing
the transaction in the anticipated timeframe or at all; whether the
collaboration between Pfizer and Arvinas will be successful;
uncertainties regarding the impact of COVID-19 on Pfizer’s
business, operations and financial results; and competitive
developments.
A further description of risks and uncertainties can be found in
Pfizer’s Annual Report on Form 10-K for the fiscal year ended
December 31, 2020 and in its subsequent reports on Form 10-Q,
including in the sections thereof captioned “Risk Factors” and
“Forward-Looking Information and Factors That May Affect Future
Results”, as well as in its subsequent reports on Form 8-K, all of
which are filed with the U.S. Securities and Exchange Commission
and available at www.sec.gov and www.pfizer.com
1 IBRANCE® (palbociclib) Prescribing Information. New York. NY:
Pfizer Inc: 2019.
2 Weinberg, RA. pRb and Control of the Cell Cycle Clock. In:
Weinberg RA, ed. The Biology of Cancer. 2nd ed. New York, NY:
Garland Science; 2014:275-329.
3 Sotillo E, Grana X. Escape from Cellular Quiescence. In:
Enders GH, ed. Cell Cycle Deregulation in Cancer. New York, NY:
Humana Press; 2010:3-22.
ContactsArvinas Investor
Contact:Will O’Connor, Stern Investor
Relationsir@arvinas.com
Arvinas Media Contact:Kirsten Owens, Arvinas
Communicationskirsten.owens@arvinas.com
Pfizer Investor Contact:Chuck Triano+1 (212)
733-3901Charles.E.Triano@Pfizer.com
Pfizer Media Contact:Eamonn Nolan+1 (212)
733-4626Eamonn.Nolan@pfizer.com
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