* Hemophilia Program: Ongoing registrational PRESent-2 and PRESent-3 studies

    of SerpinPC for the treatment of hemophilia B; PRESent-2 advancing toward
    interim analysis planned in 2024
  * Orexin Agonist Program: Clinical proof-of-concept data for ORX750 in sleep-
    deprived healthy volunteers planned in 2024
  * LockBody(®) Technology Platform: Ongoing Phase 1/2a study of LB101 (PD-
    L1xCD47) for the treatment of solid tumors

BOSTON and LONDON, March 28, 2024 (GLOBE NEWSWIRE) -- Centessa Pharmaceuticals
plc (Nasdaq: CNTA), a clinical-stage pharmaceutical company, today reported
recent business highlights and financial results for the fourth quarter and
full-year ended December 31, 2023.
"This is an exciting and pivotal time for Centessa," said Saurabh Saha MD PhD,
Chief Executive Officer of Centessa. "We are laser focused on executing the
PRESent registrational studies for SerpinPC, a potential first-in-class
subcutaneously administered therapy with a differentiated safety profile for
individuals with hemophilia B, and advancing our orexin receptor 2 (OX2R)
agonist development program into the clinic for the treatment of narcolepsy and
other sleep-wake disorders."
Dr. Saha continued, "SerpinPC's novel mechanism of action is designed to prevent
or reduce bleeding in persons with hemophilia without depleting natural
anticoagulants that help prevent blood clots. The most recent clinical data from
our ongoing Phase 2a study showed that an additional 52-weeks of continuous
treatment with SerpinPC reduced the median all-bleed ABR by 96% relative to
baseline, and no thrombosis has been observed across the study to date. Within
the PRESent registrational studies for SerpinPC, we are looking to replicate
this safety profile and meaningfully reduce bleeding rates for subjects with
hemophilia B, with or without inhibitors. We look forward to confirming a dose
and advancing to Part 2 of the PRESent-2 study this year."
"We are very excited with progress within our OX2R agonist development program,
and more specifically, ORX750, an orally administered, highly potent and
selective OX2R agonist," said Dr. Saha. "In late 2023, we shared preclinical
data that we believe support ORX750's potential to be a best-in-class oral OX2R
agonist for the treatment of narcolepsy and other sleep-wake disorders. We
remain on track with our goal to share clinical proof-of-concept data for ORX750
in sleep-deprived healthy volunteers this year."
"In parallel, we continue to evaluate our proprietary LockBody technology
platform in a first-in-human clinical study of LB101, a conditionally
tetravalent PD-L1xCD47 bispecific monoclonal antibody designed to selectively
drive CD47 into the tumor microenvironment while avoiding systemic toxicity, in
solid tumors. We look to this study to provide valuable insights regarding the
safety and tolerability of LB101, as well as the performance of our LockBody
platform in a clinical setting."
Recent Highlights

  * In December 2023 and February 2024, the Company presented data from an
    additional 52-weeks of continuous treatment from the third year (Part 5) of
    the ongoing Phase 2a study of SerpinPC, an investigational subcutaneously
    administered novel inhibitor of activated protein C (APC) for the treatment
    of hemophilia, during presentations at the American Society of Hematology
    (ASH) Annual Meeting and the 17(th) Annual Congress of the European
    Association for Haemophilia and Allied Disorders (EAHAD). Part 5 data from
    the Phase 2a study showed a continued favorable safety and tolerability
    profile for SerpinPC, as well as sustained long-term efficacy results, as

measured by a 96% reduction in the median all-bleed annualized bleeding rate (ABR) from the prospective baseline measured during the pre-exposure
observation period. To date, there have been no thromboembolic events and no

    treatment-related sustained elevations of D-dimer observed throughout the
    Phase 2a study.
  * In October 2023, the Company announced the dosing of the first subject in

its registrational PRESent-3 clinical study of SerpinPC for the treatment of

    hemophilia B with inhibitors. The Company initiated dosing in its
    registrational PRESent-2 clinical study of SerpinPC for the treatment of
    hemophilia B without inhibitors in July 2023.
  * In October 2023, the Company announced preclinical data from in vivo and in
    vitro studies of its investigational, novel OX2R agonist, ORX750, that we
    believe support a potential best-in-class profile for the treatment of
    narcolepsy and other sleep-wake disorders.

Anticipated Upcoming Program Milestones
* Hemophilia Program - The registrational PRESent-2 (hemophilia B without
inhibitors) and PRESent-3 (hemophilia B with inhibitors) studies of SerpinPC are ongoing. For PRESent-2, the Company plans to confirm a dose and advance
to Part 2 of the study based on a review of Part 1 (dose justification) data

    in 2024 (interim analysis). The primary endpoint of the PRESent-2 study is
    the rate of treated bleeds (expressed as ABR) during the first 24 weeks of
    treatment with SerpinPC (Part 2) compared to the observation period. The
    Company plans to share Part 1 data at a medical conference in late 2024 or
    early 2025.
  * Orexin Agonist Program - Upon Investigational New Drug ("IND") clearance,
    the Company plans to rapidly advance ORX750 into clinical development with

the goal of sharing clinical proof-of-concept data in sleep-deprived healthy

    volunteers in 2024.
  * LockBody Technology Platform - The Phase 1/2a first-in-human clinical study
    of LB101 (PD-L1xCD47 LockBody) is ongoing.

Where applicable, the Company plans to provide updates on preclinical programs
including follow-up orexin agonists and LB206, a PD-L1xCD3 LockBody, when they
advance toward clinical studies.
Fourth Quarter and Full-Year 2023 Financial Results
* Cash, Cash Equivalents and Short-term Investments: $256.5 million as of
December 31, 2023, which includes approximately $6.2 million in net proceeds

    through ATM sales in the fourth quarter ended December 31, 2023. In
    addition, the Company received approximately $9.7 million in net proceeds
    through ATM sales in January 2024. The Company expects its cash, cash
    equivalents and short-term investments will fund operations into 2026,
    without drawing on the remaining available tranches under the Oberland
    credit facility.
  * Research & Development Expenses: $29.7 million for the fourth quarter ended
    December 31, 2023, compared to $27.8 million for the fourth quarter ended
    December 31, 2022, and $124.4 million for the full-year 2023 compared to
    $155.1 million for the full-year 2022.
  * General & Administrative Expenses: $12.3 million for the fourth quarter
    ended December 31, 2023, compared to $13.8 million the fourth quarter ended
    December 31, 2022, and $53.7 million for the full-year 2023 compared to
    $55.2 million for the full-year 2022.

* Net Loss Attributable to Ordinary Shareholders: $36.8 million for the fourth

    quarter ended December 31, 2023, compared to $43.2 million for the fourth
    quarter ended December 31, 2022, and $151.1 million for the full-year 2023
    compared to $216.2 million for the full-year 2022.

About Centessa Pharmaceuticals
Centessa Pharmaceuticals plc (http://www.centessa.com) is a clinical-stage pharmaceutical company that aims to discover and develop medicines that are transformational for patients. Our most advanced programs include a hemophilia program, an orexin agonist program for the treatment of narcolepsy and other sleep-wake disorders and an immuno-oncology program focused on our LockBody® technology platform. We operate with the conviction that each of our programs has the potential to change the current treatment paradigm and establish a new standard of care. For more information, visit www.centessa.com (http://www.centessa.com), which does not form part of this release.
About SerpinPC
SerpinPC is an investigational subcutaneously administered novel inhibitor of
APC being developed as a potential treatment for hemophilia, regardless of
severity or inhibitor status, and which may also be developed to prevent
bleeding associated with other bleeding disorders. The registrational program
for SerpinPC in hemophilia B includes a set of clinical studies with multiple
components. PRESent-5 is an observational feeder study to collect prospective
observational data for minimum defined periods before switching to dosing
subjects in the interventional studies. The interventional studies include
PRESent-2 (moderately severe to severe hemophilia B without inhibitors, and
severe hemophilia A with or without inhibitors) and PRESent-3 (hemophilia B with
inhibitors). Additional information on the trials can be accessed at
www.clinicaltrials.gov (NCT05605678
(https://clinicaltrials.gov/study/NCT05605678), NCT05789524
(https://clinicaltrials.gov/study/NCT05789524), NCT05789537
(https://clinicaltrials.gov/study/NCT05789537)). The U.S. Food and Drug
Administration (FDA) has granted Fast Track designation to SerpinPC for the
treatment of hemophilia B, with or without inhibitors. SerpinPC has not been
approved by the FDA or any other regulatory authority for any use.
About ORX750
ORX750 is an investigational, orally administered, highly potent and selective
orexin receptor 2 (OX2R) agonist designed to directly target the underlying
pathophysiology of orexin neuron loss in narcolepsy type 1 (NT1). ORX750 has
been shown in preclinical studies to potently activate the OX2R with an in vitro
EC50 of 0.11 nM and 9,800-fold selectivity over the human orexin receptor
(hOX1R). ORX750 is Centessa's first orexin product candidate being developed for
the treatment of narcolepsy with potential expansion into other sleep-wake
disorders. ORX750 has not been approved by the FDA or any other regulatory
authority.
About the LockBody Technology Platform and LB101
Centessa's proprietary LockBody technology platform aims to redefine immuno-
oncology treatment for patients with cancer. LockBody drug candidates are
designed to selectively drive potent effector function activity, such as CD47 or
CD3, to the tumor micro-environment (TME) while avoiding systemic toxicity. The
first LockBody candidate is LB101, a conditionally tetravalent PD-L1xCD47
bispecific monoclonal antibody which has two anti-CD47 domains blocked by two
anti-PD-L1 domains, with proprietary human IgG-derived hinges linking the anti-
CD47 and anti-PD-L1 domains. The cell-killing mechanism of action, CD47, is
designed to be blocked by the PD-L1 tumor targeting domain until the IgG-derived
hinges are naturally degraded in the TME, thus unlocking and activating the CD47
effector function activity in the tumor. LB101 is in a Phase 1/2a clinical
trial. Additional information on the trial can be accessed at
www.clinicaltrials.gov (NCT05821777
(https://clinicaltrials.gov/study/NCT05821777)). LB101 is an investigational
agent that has not been approved by the FDA or any other regulatory authority.
Forward Looking Statements
This press release contains forward-looking statements. These statements may be
identified by words such as "may," "might," "will," "could," "would," "should,"
"expect," "intend," "plan," "objective," "anticipate," "believe," "estimate,"
"predict," "potential," "continue," "ongoing," "aim," "seek," 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, including
statements related to the Company's ability to discover and develop
transformational medicines for patients; its expectations for executing on the
Company's pipeline; its expectations on its anticipated cash runway; the timing
of commencement of new studies or clinical trials or clinical and preclinical
data related to SerpinPC, LB101, LB206, other LockBody candidates, the LockBody
technology platform, ORX750 and other orexin agonist molecules; its ability to
identify, screen, recruit and maintain a sufficient number of or any subjects in
its existing and anticipated studies or clinical trials including PRESent-5, the
observational feeder study, PRESent-2 and PRESent-3 and studies or trials of
LB101, LB206, and any other LockBody candidates, ORX750 and other orexin agonist
molecules and its expectations on executing its research and clinical
development plans and the timing thereof; the Company's ability to differentiate
SerpinPC, LB101, LB206, other LockBody candidates, ORX750 and other orexin
agonist molecules from other treatment options; the development, design and
therapeutic potential of SerpinPC, LB101, LB206, other LockBody candidates, the
LockBody technology platform, ORX750 and other orexin agonist molecules; and
regulatory matters, including the timing and likelihood of success of obtaining
regulatory clearance, obtaining authorizations to initiate or continue clinical
trials. Any forward-looking statements in this press release are based on our
current expectations, estimates, assumptions 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, risks related to the safety and
tolerability profile of our product candidates; our ability to identify, screen
and recruit a sufficient number of or any subjects in our existing and
anticipated new studies or clinical trials including PRESent-2, PRESent-3,
PRESent-5, and studies or trials of LB101 or within anticipated timelines; our
ability to execute IND-enabling activities in a timely manner or at all,
including with respect to ORX750 and LB206; our ability to protect and maintain
our intellectual property position; business (including commercial viability),
regulatory, economic and competitive risks, uncertainties, contingencies and
assumptions about the Company; risks inherent in developing product candidates
and technologies; future results from our ongoing and planned clinical trials;
our ability to obtain adequate financing, including through our financing
facility with Oberland, to fund our planned clinical trials and other expenses;
trends in the industry; the legal and regulatory framework for the industry,
including the receipt and maintenance of clearances to conduct or continue
clinical testing; our operating costs and use of cash, including cash runway,
cost of development activities and conducting clinical trials, future
expenditures risks; the risk that any one or more of our product candidates will
not be successfully developed and/or commercialized; the risk that the
historical results of preclinical studies or clinical studies will not be
predictive of future results in ongoing or future studies; economic risks to the
United States and United Kingdom banking systems; and geo-political risks such
as the Russia-Ukraine war or the Israeli-Palestinian conflict. These and other
risks concerning our programs and operations are described in additional detail
in our Annual Report on Form 10-K, Quarterly Reports on Form 10-Q, and our other
reports, which are on file with the U.S. Securities and Exchange Commission
(SEC). We explicitly disclaim any obligation to update any forward-looking
statements except to the extent required by law.
Contact:
Kristen K. Sheppard, Esq.
SVP of Investor Relations
investors@centessa.com

                            Centessa Pharmaceuticals plc
            Consolidated Statements of Operations and Comprehensive Loss
                                    (unaudited)
               (amounts in thousands except share and per share data)

Quarter Ended Quarter Ended Year Ended Year Ended December December December December 31, 2023 31, 2022 31, 2023 31, 2022 ---------------- ---------------- ---------------- ---------------
License and
other revenue $ 6,853 $ - $ 6,853 $ - Operating
expenses:
Research and
development 29,716 27,835 124,405 155,083 General and
administrative 12,315 13,768 53,731 55,200 Change in fair
value of
contingent
value rights - - - 1,980 ---------------- ---------------- ---------------- ---------------
Loss from
operations (35,178 ) (41,603 ) (171,283 ) (212,263 )
Interest
income 2,933 39 10,476 244 Interest
expense (2,570 ) (2,203 ) (9,906 ) (7,277 )
Other
(expense)
income, net (878 ) (70 ) (5,428 ) 2,342 ---------------- ---------------- ---------------- ---------------
Loss before
income taxes (35,693 ) (43,837 ) (176,141 ) (216,954 )
Income tax
(benefit)

 expense                 1,144             (664 )        (25,056 )           (747 )
                 ---------------- ---------------- ---------------- ---------------
 Net loss              (36,837 )        (43,173 )       (151,085 )       (216,207 )

Other
comprehensive
income (loss):
Foreign
currency
translation
adjustment 459 198 1,700 (2,185 )
Unrealized
gain on
available for
sale
securities,
net of tax 255 - 1,290 - ---------------- ---------------- ---------------- ---------------
Total
comprehensive

 loss             $    (36,123 )   $    (42,975 )   $   (148,095 )   $   (218,392 )
                 ---------------- ---------------- ---------------- ---------------

Net loss per
ordinary share
- basic and
diluted $ (0.38 ) $ (0.45 ) $ (1.57 ) $ (2.31 )
Weighted
average
ordinary
shares
outstanding -
basic and
diluted 97,923,585 94,603,860 96,177,578 93,400,513

                         Centessa Pharmaceuticals plc
                    Condensed Consolidated Balance Sheets
                                 (unaudited)
                            (amounts in thousands)
                                               December          December
                                               31, 2023          31, 2022
                                           ----------------- ----------------

Total assets:

 Cash and cash equivalents                  $       128,030   $       393,644
 Short-term investments                             128,519                 -
 Other assets                                       103,697            50,663
                                           ----------------- ----------------
 Total assets                               $       360,246   $       444,307
                                           ----------------- ----------------

Total liabilities

 Other liabilities                          $        48,302   $        38,338
 Long term debt                                      75,700            69,800
                                           ----------------- ----------------
 Total liabilities                                  124,002           108,138
                                           ----------------- ----------------
 Total shareholders' equity                         236,244           336,169
                                           ----------------- ----------------
 Total liabilities and shareholders' equity $       360,246   $       444,307
                                           ----------------- ----------------

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