Centessa Pharmaceuticals Reports Financial Results for the Third
Quarter of 2024 and Provides Business Update
- Announced additional interim data from ongoing Phase 1
clinical study of ORX750, a novel orexin receptor 2 (OX2R) agonist,
in acutely sleep-deprived healthy volunteers that further support
best-in-class potential of ORX750 in narcolepsy type 1 (NT1),
narcolepsy type 2 (NT2), and idiopathic hypersomnia (IH);
Presentation of Phase 1 data planned for medical congress in Q2
2025
- Initiated Phase 2a clinical study
of ORX750 in patients with NT1, NT2 and IH; Phase 2a data across
all three indications expected in 2025 with first-in-class
potential in NT2 and IH
- Advancing ORX142 in IND-enabling
studies for treatment of neurological, neurodegenerative, and
psychiatric disorders; Clinical data in healthy volunteers planned
for 2025
- Nominated ORX489 as third OX2R
agonist development candidate; Entering IND-enabling studies for
treatment of additional neurological, neurodegenerative, and
psychiatric disorders
- Announced strategic decision to
discontinue clinical development of SerpinPC; Net savings of
approximately $200 million to be reallocated towards expansion of
OX2R agonist franchise
BOSTON and LONDON, Nov. 12, 2024 (GLOBE NEWSWIRE) -- Centessa
Pharmaceuticals plc (Nasdaq: CNTA), a
clinical-stage pharmaceutical company with a mission to
discover, develop and ultimately deliver medicines that
are transformational for patients, today reported financial
results for the third quarter ended September 30, 2024, and
provided a business update.
“The totality of data across our OX2R agonist program continues
to reinforce the strength of our discovery engine and the
therapeutic potential of these assets across a broad spectrum of
disorders,” said Saurabh Saha MD PhD, Chief Executive Officer of
Centessa. “The Phase 1 interim data for ORX750, now updated to
include over 70 subjects dosed with ORX750, continue to support its
best-in-class potential in NT1, NT2 and IH. Based on the strength
of these interim data, we recently initiated a Phase 2a clinical
study of ORX750 in patients with NT1, NT2 and IH. Similar to our
Phase 1 study, which enabled a move from IND clearance to clinical
data in the course of a few months, we expect our Phase 2a study
design to generate clinical data for all three indications in 2025
and enable dose selection for future pivotal studies with the
potential to be first-in-class in NT2 and IH.”
Dr. Saha continued, “In addition to ORX750, we
are advancing a growing pipeline of OX2R agonists targeting
excessive daytime sleepiness (EDS) in neurological,
neurodegenerative, and psychiatric disorders, as well as other
potential symptoms including impaired attention, cognitive
deficits, and fatigue. ORX142 is currently in IND-enabling studies,
and subject to IND clearance, we expect to initiate clinical
development and share clinical data in acutely sleep-deprived
healthy volunteers in 2025. We’re also pleased to be kicking off
our next wave of candidates with ORX489, our most potent OX2R
agonist to date based on preclinical data, which is entering
IND-enabling studies.”
Interim Data from Ongoing Phase 1 Clinical Study of
ORX750
The additional interim data from the ongoing Phase 1 clinical
trial of ORX750 in healthy volunteers includes results from two
single-ascending dose (SAD) cohorts at 3.5 mg (n=12: 9 active, 3
placebo) and 5.0 mg (n=12: 9 active, 3 placebo), a cohort of
acutely sleep-deprived healthy volunteers within the cross-over
assessment at 3.5 mg (n=10) administered as a single oral dose, and
two multiple-ascending dose (MAD) cohorts at 2.0 mg (n=10: 8
active, 2 placebo) and 3.0 mg (n=10: 8 active, 2 placebo). The
interim data showed:
- Significantly increased wakefulness in
acutely sleep-deprived healthy volunteers compared to placebo at
all doses tested, with a clear dose dependent response. Treatment
with ORX750 resulted in statistically significant (p<0.05) and
clinically meaningful increased sleep latency in the Maintenance of
Wakefulness Test (MWT) (time to sleep onset over the four sessions
performed at ~2, 4, 6, and 8 hours after dosing at 11 p.m., maximum
40 minutes per session) compared to placebo at all doses tested.
The 3.5 mg dose was shown to restore normative
wakefulness1 with a mean sleep latency of 34 minutes and
a placebo-adjusted mean sleep latency of 20 minutes, as measured by
the MWT.
Interim Data from Ongoing Phase 1 Clinical Study of
ORX750
(as of October 31, 2024 data cutoff date) |
|
|
ORX750
LS Mean (95% CI)
Sleep Latency
(Minutes) |
Placebo
LS Mean (95% CI)
Sleep Latency
(Minutes) |
LS Mean Difference
Compared to
Placebo (95% CI) |
p-Value |
1.0 mg
(n=8) |
18 (12, 23) |
10 (4, 15) |
8 (0, 16) |
p=0.04 |
2.5 mg
(n=8) |
32 (22, 42) |
17 (7, 27) |
15 (5, 26) |
p=0.01 |
3.5 mg
(n=10) |
34 (27, 40) |
13 (7, 20) |
20 (15, 25) |
p<0.0001 |
- A favorable safety and tolerability profile with all observed
treatment-emergent adverse events (AEs) being mild and transient
with none leading to treatment discontinuation. No cases of
hepatotoxicity or visual disturbances were observed. Additionally,
there were no clinically significant treatment-emergent changes in
hepatic and renal parameters, vital signs, or electrocardiogram
(ECG) parameters.
Interim
Safety Data from Ongoing Phase 1 Clinical Study of
ORX750
(as of October 31, 2024 data cutoff date) |
| |
|
|
SAD Cohorts |
MAD Cohorts |
|
|
Placebo
(n=15) |
ORX750
1.0 mg
(n=9) |
ORX750
2.0 mg
(n=9) |
ORX750
2.5 mg
(n=9) |
ORX750
3.5 mg
(n=9) |
ORX750
5.0 mg
(n=9) |
Placebo
(n=4) |
ORX750
2.0 mg
(n=8) |
ORX750
3.0 mg
(n=8) |
|
Any TEAE, n (%) |
4 (27) |
3 (33) |
3 (33) |
1 (11) |
0 |
3 (33) |
2 (50) |
4 (50) |
3 (38) |
Related
|
4 (27)
|
0
|
2 (22)
|
1 (11)
|
0
|
2 (22)
|
1 (25)
|
4 (50)
|
2 (25)
|
|
Nonrelated |
1 (7) |
3 (33) |
2 (22) |
0 |
0 |
2 (22) |
2 (50) |
2 (25) |
1 (12) |
Mild
|
4 (27)
|
3 (33)
|
3 (33)
|
1(11)
|
0
|
3 (33)
|
2 (50)
|
4 (50)
|
3 (38)
|
|
Moderate |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
Severe |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
TEAEs leading to discontinuation, n (%) |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
Serious TEAEs, n (%) |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
Frequently reported AEs associated with other OX2R
agonists
|
|
|
|
|
|
|
|
|
|
|
Insomnia |
0 |
0 |
0 |
0 |
0 |
0 |
1 (25) |
2 (25) |
0 |
|
Urinary frequency/urgency |
1 (7) |
0 |
0 |
0 |
0 |
1 (11) |
0 |
1 (12) |
1 (12) |
|
Visual disturbances |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
Hepatotoxicity |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
Blood pressure increased |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
|
|
Treatment-emergent adverse event (TEAE). Safety data from
Sleep Study Cohorts was consistent with SAD. Nonrelated includes
unlikely related and not related. Related includes probably and
possibly related. |
|
|
- An encouraging linear pharmacokinetic (PK) profile that
supports the use of ORX750 as a once-daily oral dosing regimen with
rapid absorption (plasma concentrations of ORX750 peaked 2h after
the first dose). The systemic exposure of ORX750 increased in a
dose-proportional manner.
The Phase 1 study is ongoing as dose escalation is continuing in
the acutely sleep-deprived cross-over assessment, SAD and MAD
portions of the study.
Phase 2a Clinical Study of ORX750
The Phase 2a study is a randomized, double-blind,
placebo-controlled, cross-over basket study to evaluate the safety,
tolerability, and PK of ORX750 in patients with NT1, NT2, and IH.
There will be separate cohorts for each indication. Initial dosing
for NT1 will be 1.0 mg and for NT2 and IH will be 2.0 mg with
sequential dose escalation/de-escalation between cohorts. Each
dosing cohort consists of a 6-week treatment duration with
crossover study design. During the 6 weeks of treatment, each
participant will be randomized to one of two blinded treatment
sequences and receive a total of 4 weeks of treatment with ORX750
and 2 weeks of treatment with placebo. Efficacy assessments will
evaluate the effect of ORX750 on excessive daytime sleepiness
(using the MWT and Epworth Sleepiness Scale (ESS)), cataplexy (NT1
patients only), and overall symptom improvement (measured by
Narcolepsy Severity Scale (NSS) and Idiopathic Hypersomnia Severity
Scale (IHSS)). Other exploratory assessments include measures of
sleep, cognition, attention, memory, and general health.
“The Phase 2a study of ORX750 is intended to accelerate overall
timelines and inform future registrational studies,” said Mario
Alberto Accardi PhD, President of Centessa’s Orexin Program. “This
well-powered study leverages highly innovative design elements
which we believe have the potential to enable efficient data
generation with an optimal number of patients in each indication.
With this design, all participating patients will receive ORX750
for at least 4 weeks. We aim to generate data across all three
indications in 2025, which could enable ORX750 to be first-in-class
in NT2 and IH.”
SerpinPC Clinical Program Update
The Company has made a strategic and data-driven decision to
discontinue the global clinical development of SerpinPC, a novel
inhibitor of activated protein C that was being evaluated for the
treatment of hemophilia B. This action was driven by the Company’s
decision to prioritize capital toward the development of its OX2R
agonist program and the outcome of a planned interim analysis of
Part 1 of the PRESent-2 study of SerpinPC. Within the interim
analysis, SerpinPC was observed to have a favorable safety and
tolerability profile; however, the Company determined that
additional time and investment would be required to further develop
SerpinPC with a more competitive profile for the treatment of
hemophilia B in light of the evolving treatment and market
landscape for hemophilia B, including the recent FDA approval of a
competing product. The Company would like to thank the hemophilia
community and all the patients, caregivers and physicians who
participated in the SerpinPC clinical trials. The Company is now
exploring potential strategic alternatives for SerpinPC.
“Moving forward, we intend to prioritize our resources and
reallocate net savings of approximately $200 million associated
with the planned commercial launch of SerpinPC towards expanding
our potential best-in-class OX2R agonist franchise, where we see
significant opportunities to both address unmet patient needs and
create shareholder value,” stated John Crowley, Chief Financial
Officer. “With a cash runway that extends into mid-2027, we believe
Centessa is well positioned to support our OX2R agonist franchise
through multiple, potential value-creating milestones.”
Recent Highlights
- In September, the Company presented preclinical data from
non-human primate studies of ORX142 at the 27th Congress
of the European Sleep Research Society (Sleep Europe 2024).
- In September, the Company completed an upsized underwritten
public offering of 17,542,372 American Depositary Shares (ADSs) in
the aggregate, at a price to the public of $14.75 per ADS,
resulting in net proceeds of approximately $242.7 million, which
included the underwriters’ over-allotment option to purchase
additional shares.
- In September, the Company announced positive interim data from
the ongoing Phase 1 clinical trial of ORX750 in acutely
sleep-deprived healthy volunteers as of an August 26, 2024 data
cutoff date.
Anticipated Upcoming Program
Milestones
- OX2R Agonist Program –
- ORX750: Subject to acceptance, a presentation
of Phase 1 clinical data is planned at a medical conference in the
second quarter of 2025. The Company expects to share Phase 2a data
for NT1, NT2 and IH in 2025.
- ORX142: Advancing through IND-enabling
studies. The Company is focused on obtaining IND clearance and
initiating clinical development with the goal of sharing clinical
data in acutely sleep-deprived healthy volunteers in 2025.
- ORX489: Entering IND-enabling
studies.
- OX2R Agonist Pipeline: Progressing additional
OX2R agonists as well as research efforts on differentiated
pharmacology associated with the activation of the orexin
system.
- LockBody Technology Platform – LB101
(PD-L1xCD47 LockBody) is in an ongoing Phase 1/2a first-in-human
clinical study for the treatment of solid tumors.
Third Quarter 2024 Financial Results
- Cash, Cash Equivalents and
Short-term Investments: $518.4 million as of September 30,
2024. The Company expects its cash, cash equivalents and short-term
investments as of September 30, 2024 will fund operations into
mid-2027.
- Research
& Development Expenses: $33.9 million for the third
quarter ended September 30, 2024, compared to $28.2 million for the
third quarter ended September 30, 2023.
- General
& Administrative Expenses: $12.5 million for the third
quarter ended September 30, 2024, compared to $12.0 million for the
third quarter ended September 30, 2023.
- Net Loss
Attributable to Ordinary Shareholders: $42.6 million for
the third quarter ended September 30, 2024, compared to $38.6
million for the third quarter ended September 30, 2023.
1. Doghramji K, et al., A
normative study of the maintenance of wakefulness test (MWT).
Electroencephalogr Clin Neurophysiol 1997;
103:554-62.
About Centessa Pharmaceuticals
Centessa Pharmaceuticals plc is a clinical-stage
pharmaceutical company that aims to discover and develop medicines
that are transformational for patients. We are developing potential
best-in-class orexin receptor 2 (OX2R) agonists intended to be
orally administered for the treatment of sleep-wake disorders
including narcolepsy type 1 (NT1), narcolepsy type 2 (NT2) and
idiopathic hypersomnia (IH), and excessive daytime sleepiness (EDS)
in neurological, neurodegenerative, and psychiatric conditions. We
also anticipate that our orexin agonists may have utility in
treating impaired attention, cognitive deficits, fatigue, and other
symptoms. Our lead OX2R agonist, ORX750, is currently being
evaluated in Phase 1 and Phase 2 clinical trials for NT1, NT2 and
IH. ORX750 has not been approved by the FDA or any other regulatory
authority. 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. LB101 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 ORX750, ORX142,
ORX489 and other OX2R agonist molecules, LB101, other LockBody
candidates, and the LockBody technology platform; its ability to
identify, screen, recruit and maintain a sufficient number of or
any subjects in its existing and anticipated studies or clinical
trials of ORX750, ORX142, ORX489 and other OX2R agonist molecules,
LB101 and any other LockBody candidates; its expectations on
executing its research and clinical development plans and the
timing thereof; its expectations as to the potential results and
impact of each of its clinical programs and trials; the Company’s
ability to differentiate ORX750, ORX142, ORX489 and other OX2R
agonist molecules, LB101, other LockBody candidates from other
treatment options; the development, design and therapeutic
potential of ORX750, ORX142, ORX489 and other OX2R agonist
molecules, LB101, other LockBody candidates and the LockBody
technology platform; the anticipated net savings associated with
the discontinuation of the SerpinPC program; 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 of
ORX750, ORX142, ORX489 or LB101 or within anticipated timelines;
our expectations relating to the clinical trials 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 Ended
September 30, 2024 |
|
Three Months Ended
September 30, 2023 |
|
Nine Months Ended
September 30, 2024 |
|
Nine Months Ended
September 30, 2023 |
| Operating expenses: |
|
|
|
|
|
|
|
|
Research and development |
$ |
33,903 |
|
|
$ |
28,190 |
|
|
$ |
89,370 |
|
|
$ |
94,689 |
|
|
General and administrative |
|
12,502 |
|
|
|
12,019 |
|
|
|
37,105 |
|
|
|
41,416 |
|
| Loss from operations |
|
(46,405 |
) |
|
|
(40,209 |
) |
|
|
(126,475 |
) |
|
|
(136,105 |
) |
|
Interest income |
|
3,340 |
|
|
|
2,953 |
|
|
|
9,171 |
|
|
|
7,543 |
|
|
Interest expense |
|
(2,557 |
) |
|
|
(2,541 |
) |
|
|
(7,611 |
) |
|
|
(7,336 |
) |
|
Other income (expense), net |
|
3,664 |
|
|
|
(1,677 |
) |
|
|
2,281 |
|
|
|
(4,550 |
) |
| Loss before income taxes |
|
(41,958 |
) |
|
|
(41,474 |
) |
|
|
(122,634 |
) |
|
|
(140,448 |
) |
|
Income tax expense (benefit) |
|
608 |
|
|
|
(2,826 |
) |
|
|
1,794 |
|
|
|
(26,200 |
) |
| Net loss |
|
(42,566 |
) |
|
|
(38,648 |
) |
|
|
(124,428 |
) |
|
|
(114,248 |
) |
| |
|
|
|
|
|
|
|
| Other comprehensive income
(loss): |
|
|
|
|
|
|
|
|
Foreign currency translation adjustment |
|
(412 |
) |
|
|
(419 |
) |
|
|
(498 |
) |
|
|
1,241 |
|
|
Unrealized gain on available for sale securities, net of tax |
|
912 |
|
|
|
252 |
|
|
|
1,100 |
|
|
|
1,035 |
|
| Other comprehensive income
(loss) |
|
500 |
|
|
|
(167 |
) |
|
|
602 |
|
|
|
2,276 |
|
| |
|
|
|
|
|
|
|
| Total comprehensive loss |
$ |
(42,066 |
) |
|
$ |
(38,815 |
) |
|
$ |
(123,826 |
) |
|
$ |
(111,972 |
) |
|
|
|
|
|
|
|
|
|
| Net loss per ordinary share -
basic and diluted |
$ |
(0.37 |
) |
|
$ |
(0.40 |
) |
|
$ |
(1.15 |
) |
|
$ |
(1.20 |
) |
| Weighted average ordinary
shares outstanding - basic and diluted |
|
116,253,902 |
|
|
|
96,648,110 |
|
|
|
108,571,742 |
|
|
|
95,589,181 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Centessa Pharmaceuticals plc
Condensed Consolidated Balance Sheets
(unaudited)
(amounts in thousands) |
| |
| |
September 30, 2024 |
|
December 31, 2023 |
| Total assets: |
|
|
|
|
Cash and cash equivalents |
$ |
395,026 |
|
|
$ |
128,030 |
|
|
Short-term investments |
|
123,423 |
|
|
|
128,519 |
|
|
Other assets |
|
91,266 |
|
|
|
103,697 |
|
|
Total assets |
$ |
609,715 |
|
|
$ |
360,246 |
|
| |
|
|
|
| Total liabilities |
|
|
|
|
Other liabilities |
$ |
34,878 |
|
|
$ |
48,302 |
|
|
Long term debt |
|
75,700 |
|
|
|
75,700 |
|
|
Total liabilities |
|
110,578 |
|
|
|
124,002 |
|
| |
|
|
|
|
Total shareholders’ equity |
|
499,137 |
|
|
|
236,244 |
|
|
Total liabilities and shareholders' equity |
$ |
609,715 |
|
|
$ |
360,246 |
|
|
|
|
|
|
|
|
|
|
A photo accompanying this announcement is available at
https://www.globenewswire.com/NewsRoom/AttachmentNg/46d719f5-271c-4504-9151-9da45a7837e8
Centessa Pharmaceuticals (LSE:0ACX)
과거 데이터 주식 차트
부터 11월(11) 2024 으로 12월(12) 2024
Centessa Pharmaceuticals (LSE:0ACX)
과거 데이터 주식 차트
부터 12월(12) 2023 으로 12월(12) 2024
