Centessa Pharmaceuticals plc (“Company”) (Nasdaq: CNTA), together
with subsidiary ApcinteX Limited (“ApcinteX”), today announced
positive topline results from the Phase 2a part of AP-0101, the
six-month repeat dose portion of its ongoing first-in-human
proof-of-concept study evaluating SerpinPC in severe hemophilia A
and B patients.
AP-0101 is a Phase 1/2a proof-of-concept study evaluating
SerpinPC, an inhibitor of activated protein C (“APC”), in 23 male
subjects with either severe hemophilia A or B who were not on
prophylaxis.1 The Phase 2a part of the study assessed the safety,
tolerability and pharmacokinetics across three dose cohorts (0.3
mg/kg, 0.6 mg/kg and 1.2 mg/kg) of SerpinPC administered as a
subcutaneous (SC) injection every 4 weeks over a 24-week period (6
total doses). Reduction in the annualized bleeding rates (ABRs)
were exploratory outcomes. Although eligible, none of the patients
in the study had inhibitors.
SerpinPC was well-tolerated. As previously disclosed, one
subject with a history of a skin disorder discontinued treatment on
SerpinPC due to an injection site reaction. No other
SerpinPC-related adverse events have been recorded. There was no
reported sustained elevation in D-dimer, a sensitive measure of
excess thrombin generation, throughout the 24-week study. Two
subjects had anti-drug antibodies and remained on treatment without
apparent impact on ABRs.
In the highest dose cohort, SerpinPC reduced the self-reported
all bleeds ABR by 88% during the last 12 weeks of treatment
(pre-specified primary assessment period) as compared to the all
bleeds ABR prospectively measured during the pre-exposure
observation period. In the highest dose cohort, five out of eight
subjects had zero or one bleed during the 12-week pre-specified
primary assessment period. Self-reported spontaneous joint bleeds
ABR was reduced by 94% in the highest dose cohort. ABR reductions
were similar between patients with either hemophilia A or
hemophilia B.
|
Dose Tested |
Exploratory Efficacy Endpoints |
0.3 mg/kgn=7 |
0.6 mg/kgn=7 |
1.2 mg/kgn=8 |
All Bleeds ABR (median percent change) |
-80%p=0.016 |
-70%p=0.031 |
-88%p=0.016 |
Spontaneous Joint Bleeds ABR (median percent
change) |
-76%p=0.016 |
-69%p=0.031 |
-94%p=0.023 |
Above analyses compared last 12 weeks of treatment (pre-specified
primary assessment period) topre-exposure baseline measures.
Bleeding events were self-reported.p-values presented are based on
small numbers and are exploratory in nature. |
The median number of target joints (joint with >3 bleeds in
any 6-month period) was reduced to zero at the end of the study
from a pre-exposure baseline of 2.5. All subjects had target joints
at the start of the study and 15 subjects had zero target joints at
the end of the study.
All 22 patients who completed the Phase 2a portion of the study
have elected to enroll into the 48-week open label extension
(“OLE”) portion of the study in which a single flat 60 mg
subcutaneous dose of SerpinPC will be administered every 4 weeks
over a period of 48 weeks (13 doses total). Centessa expects to
report results from the OLE portion of this study in the second
half of 2022.
“The compelling reduction in bleeds and continued tolerability
that we observed in both hemophilia A and hemophilia B patients in
this proof-of-concept study are very encouraging, and we are eager
to move SerpinPC into a global development plan aimed at pursuing
one or more registrations. We see broad utility of SerpinPC across
the hemophilia landscape and will seek the most rapid path to bring
this potential subcutaneous therapy to hemophilia patients,” said
Antoine Yver, M.D., M.Sc., Chief Medical Officer of Centessa
Pharmaceuticals.
“The results of this Phase 2a study of SerpinPC continue to show
an excellent tolerability profile for this molecule, and the
exploratory efficacy results seen in this study of severe
hemophilia A and B patients are also very promising. A safe,
subcutaneous, prophylaxis option for both hemophilia A and B
patients would be an important addition to our treatment choices,”
said David Lillicrap, M.D., Professor of Pathology and Molecular
Medicine at Queen's University, Kingston, Ontario, Canada and
previously a World Federation of Hemophilia Advisory Board
member.
¹ Clinicaltrials.gov identifier: NCT04073498
(https://clinicaltrials.gov/ct2/show/NCT04073498)
Conference Call and
WebcastCentessa Pharmaceuticals will host a webcast and
conference call today, September 9, 2021, at 8:30 a.m. EDT to
discuss topline data from the proof-of-concept trial. To access the
audio webcast with slides, please visit the "Events &
Publications" page in the Investors & Media section of the
Company's website
at https://investors.centessa.com/events-presentations. The
call can also be accessed by dialing (855) 493-3565 (domestic) or
(929) 517-9002 (international) with conference ID 8459296. An
archive of today's webcast will be available on the Company’s
website.
About Centessa PharmaceuticalsCentessa
Pharmaceuticals plc aims to bring impactful new medicines to
patients by combining the strengths of an asset-centric model with
the benefits of scale and diversification typical of larger R&D
organizations. The asset-centric model refers to a highly
specialized, singular-focused company that is led by a team of
well-recognized subject matter experts. Centessa’s asset-centric
companies’ programs range from discovery-stage to late-stage
development and include diverse therapeutic areas such as oncology,
hematology, immunology/inflammation, neuroscience, hepatology,
pulmonology and nephrology. For more information, visit
www.centessa.com.
About ApcinteX
LimitedApcinteX Limited is focused on developing SerpinPC
for the treatment of hemophilia A and hemophilia B. Hemophilia is a
rare bleeding disorder that is caused by a deficiency of thrombin
generation upon vascular damage.
About SerpinPCSerpinPC, a biologic based on the
serpin family of proteins, is designed to allow more thrombin to be
generated by inhibiting activated protein C (APC) thus rebalancing
coagulation in hemophilia patients. SerpinPC has the potential to
treat all types of hemophilia regardless of severity or inhibitor
status, and may also prevent bleeding associated with other
bleeding disorders.
About AP-0101 AP-0101 is an ongoing Phase 1/2a
open-label clinical trial to investigate the safety, tolerability
and pharmacokinetics of intravenous and subcutaneous doses of
SerpinPC in healthy male volunteers and male persons with severe
hemophilia (https://clinicaltrials.gov/ct2/show/NCT04073498).
About Hemophilia A (HA) and
Hemophilia B (HB)HA and HB are X-linked genetic
disorders affecting one in 5,000 and one in 20,000 live male
births, respectively, resulting in spontaneous internal bleeding
that can be life-threatening. More than 70% of bleeds occur into
joints (hemarthrosis) causing chronic joint damage (arthropathy)
with musculoskeletal destruction. The bleeding associated with
these disorders is the result of a defect or deficiency in factor
VIII (in the case of HA) or factor IX (in the case of HB), the two
components of the intrinsic tenase complex.
Normal blood coagulation (hemostasis)
is a crucial part of the physiological response to tissue damage.
When blood components come into contact with extravascular cells
and proteins, platelets accumulate and ultimately lead to the
formation of thrombin, the effector enzyme of blood coagulation.
Prothrombinase activity is required for the rapid, localized
production of thrombin needed for adequate blood clotting.
Prothrombinase is continuously degraded by APC, which is present in
the circulation at low concentrations. In the setting of deficient
intrinsic tenase activity (hemophilia), the natural anticoagulant
activity of the circulating APC results in insufficient
prothrombinase activity for normal blood clotting.
Forward Looking
Statements This press release contains
forward-looking statements. These statements may be identified by
words such as "believe," "anticipate," "plan," "expect," "intend,"
"will," "may," "goal," "project," "estimate," "potential," and
variations of these words or similar expressions that are intended
to identify forward-looking statements. Any such statements in this
press release that are not statements of historical fact may be
deemed to be forward-looking statements. These statements include
discussions of the open label extension study of SerpinPC and its
design and conduct; plans for continued development of SerpinPC,
including our global development plan and registrational path for
this candidate; our expectations with respect to the treatment
paradigm for hemophilia A and B; our ability to deliver impactful
medicines to patients; the ability of our key executives to drive
execution of our portfolio of programs; our asset-centric business
model and the intended advantages and benefits thereof; research
and clinical development plans; the scope, progress, results and
costs of developing our product candidates or any other future
product candidates; strategy; regulatory matters, including the
timing and likelihood of success of obtaining approvals to initiate
or continue clinical trials or market any products; market size and
opportunity; and our ability to complete certain milestones.
Any forward-looking statements in this
press release are based on our current expectations, estimates and
projections only as of the date of this release and are subject to
a number of risks and uncertainties that could cause actual results
to differ materially and adversely from those set forth in or
implied by such forward-looking statements. These risks and
uncertainties include, but are not limited to, the safety,
tolerability and efficacy profile of SerpinPC observed to date may
change adversely in future clinical trials, ongoing analyses of
trial data or subsequent to commercialization; foreign regulatory
agencies may not agree with our regulatory approval strategies,
components of our filings, such as clinical trial designs, conduct
and methodologies, or the sufficiency of data submitted; risks
inherent in developing products and technologies; risks related to
our ability to protect and maintain our intellectual property
position; business, regulatory, economic and competitive risks,
uncertainties, contingencies and assumptions about the Company; our
ability to obtain adequate financing to fund our planned clinical
trials and other expenses; trends in the industry; the legal and
regulatory framework for the industry; future expenditures risks
related to our asset-centric corporate model; the risk that any one
or more of our product candidates will not be successfully
developed and commercialized; the risk that the results of
preclinical studies or clinical studies will not be predictive of
future results in connection with future studies; and risks related
to the COVID-19 pandemic including the effects of the Delta
variant. These and other risks concerning our programs and
operations are described in additional detail in our most recent
Form 10-Q, which is on file with the SEC and available on the SEC’s
website at www.sec.gov. We operate in a very competitive
environment in which new risks emerge from time to time. These
forward-looking statements are based on our current expectations,
and speak only as of the date hereof. We explicitly disclaim any
obligation to update any forward-looking statements except to the
extent required by law.
Contacts:
Investor Contact: |
Media Contacts: |
Jennifer Porcelli, Head of
Investor Relations |
US |
Centessa Pharmaceuticals |
Dan Budwick, 1AB |
jennifer.porcelli@centessa.com |
dan@1abmedia.com |
|
|
|
UK/Greater
Europe |
|
Mary Clark, Optimum Strategic
Communications |
|
centessa@optimumcomms.com |
|
|
|
Switzerland |
|
Marcus Veith, VEITHing
Spirit |
|
marcus@vspirit.ch |
|
M: +41 79 20 75 111 |
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