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)

 

 

ORX750LS Mean (95% CI)Sleep Latency (Minutes)

PlaceboLS Mean (95% CI)Sleep Latency (Minutes)

LS Mean DifferenceCompared 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)

ORX7501.0 mg(n=9)

ORX7502.0 mg(n=9)

ORX7502.5 mg(n=9)

ORX7503.5 mg(n=9)

ORX7505.0 mg(n=9)

Placebo(n=4)

ORX7502.0 mg(n=8)

ORX7503.0 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

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