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

    of SerpinPC for the treatment of hemophilia B; PRESent-2 interim analysis
    planned in 2024
  * Orexin Agonist Program: Cleared IND and initiated Phase 1 first-in-human

clinical trial of ORX750, a highly potent and selective OX2R agonist for the

    treatment of narcolepsy; Clinical proof-of-concept data in acutely sleep-
    deprived healthy volunteers planned in 2H of 2024
  * LockBody(®) Technology Platform: Ongoing Phase 1/2a study of LB101 (PD-
    L1xCD47) for the treatment of solid tumors
  * Cash runway, extended by recent public offering, supports clinical plans
    through multiple data readouts

BOSTON and LONDON, May 13, 2024 (GLOBE NEWSWIRE) -- Centessa Pharmaceuticals plc
(Nasdaq: CNTA), a clinical-stage pharmaceutical company that aims to discover
and develop medicines that are transformational for patients, today reported
financial results and business highlights for the first quarter ended March
31, 2024.
"2024 is off to a strong start for Centessa. Following clearance of our IND, we
recently initiated the Phase 1 first-in-human, clinical trial of ORX750, a
highly potent and selective orexin receptor 2 (OX2R) agonist for the treatment
of narcolepsy, and remain on track with our goal to share proof-of-concept data
in acutely sleep-deprived healthy volunteers in the second half of this year,"
said Saurabh Saha MD PhD, Chief Executive Officer of Centessa. "We believe this
study has the potential to deliver robust translational results that could lay
the foundation for an orexin agonist clinical development program targeting
narcolepsy Type 1 and Type 2 with the potential to expand into other sleep-wake
disorders including idiopathic hypersomnia, as well as broader neurological
indications. Additionally, the PRESent registrational studies for SerpinPC for
the treatment of hemophilia B are progressing, and we plan to conduct an interim
analysis of the PRESent-2 study later this year."
Dr. Saha continued, "We are thrilled to now be progressing all three of our most
advanced pipeline programs in clinical studies focused on areas with significant
unmet need, including hemophilia B, sleep-wake disorders, and solid tumors. With
our recently strengthened balance sheet, we believe we are well positioned to
execute on our clinical plans through multiple clinical readouts."
Recent Highlights

  * In April and May, the Company completed an underwritten public offering of
    12,390,254 American Depositary Shares ("ADSs") in the aggregate, at a price
    to the public of $9.25 per ADS, resulting in net proceeds of approximately
    $107.2 million, which included the underwriters' over-allotment option to
    purchase additional shares.
  * In April, the Company announced that the U.S. Food and Drug Administration
    (FDA) cleared the Investigational New Drug application (IND) to initiate a
    Phase 1 first-in-human (FIH), clinical trial of ORX750 for the treatment of
    narcolepsy.
  * In February, the Company presented data 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 an oral presentation at 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.

Anticipated Upcoming Program Milestones

  * Hemophilia Program - The registrational 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) studies of

SerpinPC are ongoing. For PRESent-2, the Company plans to review Part 1 data

    in 2024 (interim analysis) with the goal of confirming a dose and advancing
    to Part 2 of the study. 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 - The Phase 1 FIH clinical study of ORX750, which is
    being progressed for the treatment of narcolepsy, has been initiated. The
    Company expects to share clinical proof-of-concept data in acutely sleep-
    deprived healthy volunteers in 2H of 2024.
  * LockBody Technology Platform - The Phase 1/2a FIH clinical study of LB101
    (PD-L1xCD47 LockBody) for the treatment of solid tumors is ongoing.

Where applicable, the Company plans to provide updates on preclinical assets
including follow-up orexin agonists and LB206, a PD-L1xCD3 LockBody, when they
advance toward clinical studies.
First Quarter 2024 Financial Results

  * Cash, Cash Equivalents and Short-term Investments: $230.2 million as of
    March 31, 2024. The Company expects its cash, cash equivalents and short-
    term investments as of March 31, 2024, in combination with approximately

$107.2 million in aggregate net proceeds from our offering of ADSs completed

    in April and May 2024, will fund operations into mid-2026, without drawing
    on the remaining available tranches under the Oberland credit facility.
  * Research & Development Expenses: $22.7 million for the first quarter ended
    March 31, 2024, compared to $32.8 million for the first quarter ended March
    31, 2023.

* General & Administrative Expenses: $13.4 million for the first quarter ended

    March 31, 2024, compared to $16.1 million for the first quarter ended March
    31, 2023.
  * Net Loss Attributable to Ordinary Shareholders: $38.0 million for the first
    quarter ended March 31, 2024, compared to $50.7 million for the first
    quarter ended March 31, 2023.

About Centessa Pharmaceuticals
Centessa Pharmaceuticals plc 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, 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, NCT05789524, 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
Centessa's first orexin development candidate is ORX750, 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), with potential applicability to
narcolepsy type 2 (NT2), idiopathic hypersomnia (IH), and other sleep-wake
disorders with normal orexin levels. 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 in a
Phase 1 clinical study for the treatment of narcolepsy. 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.
Centessa's 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). 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, 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 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, other LockBody candidates, ORX750 and other orexin agonist
molecules from other treatment options; the development, design and therapeutic
potential of SerpinPC, LB101, 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 and ORX750 or within anticipated timelines; our expectations
relating to the Phase 1 first-in-human, clinical trial of ORX750, including the
predicted timing of enrollment, the predicted efficacious doses of ORX750 and
our ability to successfully conduct our clinical development of ORX750, 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 Middle East conflicts. 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)
                                                 Three Months     Three Months
                                                    Ended            Ended
                                                March 31, 2024   March 31, 2023
                                               ---------------- ---------------

Operating expenses:

 Research and development                       $     22,652     $     32,826
 General and administrative                           13,438           16,051
                                               ---------------- ---------------
 Loss from operations                                (36,090 )        (48,877 )
 Interest income                                       2,591            2,531
 Interest expense                                     (2,529 )         (2,345 )
 Other expense, net                                   (1,537 )         (1,346 )
                                               ---------------- ---------------
 Loss before income taxes                            (37,565 )        (50,037 )
 Income tax expense                                      481              677
                                               ---------------- ---------------
 Net loss                                            (38,046 )        (50,714 )
                                               ---------------- ---------------

Other comprehensive income (loss):
Foreign currency translation adjustment (25 ) 898
Unrealized gain on available for sale

 securities, net of tax                                  155                -
                                               ---------------- ---------------
 Other comprehensive income                              130              898
                                               ---------------- ---------------
                                               ---------------- ---------------
 Total comprehensive loss                       $    (37,916 )   $    (49,816 )
                                               ---------------- ---------------

Net loss per ordinary share - basic and

 diluted                                        $      (0.38 )   $      (0.53 )
                                               ---------------- ---------------

Weighted average ordinary shares outstanding

 - basic and diluted                              99,887,720       94,937,904
                      Centessa Pharmaceuticals plc
                 Condensed Consolidated Balance Sheets
                              (unaudited)
                         (amounts in thousands)
                                               March        December
                                             31, 2024       31, 2023
                                           ------------- --------------

Total assets:

 Cash and cash equivalents                  $ 118,218     $ 128,030
 Short-term investments                       111,959       128,519
 Other assets                                  97,994       103,697
                                           ------------- --------------
 Total assets                               $ 328,171     $ 360,246
                                           ------------- --------------

Total liabilities

 Other liabilities                          $  36,208     $  48,302
 Long term debt                                76,800        75,700
                                           ------------- --------------
 Total liabilities                            113,008       124,002
                                           ------------- --------------
 Total shareholders' equity                   215,163       236,244
                                           ------------- --------------
 Total liabilities and shareholders' equity $ 328,171     $ 360,246
                                           ------------- --------------

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