Centessa Pharmaceuticals plc (CNTA)

Item 1. Business

In this Annual Report on Form 10-K, unless otherwise indicated or the context otherwise requires, all references to “we,” “our,” “us,” “Centessa,” “the Company,” and “our Company” refer to Centessa Pharmaceuticals plc and its consolidated subsidiaries.

Overview

Our strategy is a pipeline-in-a-pathway approach: we leverage our deep understanding of the orexin pathway, differentiated structural biology and translational insights with the aim to develop and scale a franchise of novel OX2R agonists across sleep-wake disorders and other neurological, neurodegenerative and neuropsychiatric disorders with significant unmet need. We believe this pathway-centric model positions us to deliver transformational medicines, establish leadership in orexin-based neuroscience, and create durable long-term value.

Our most advanced product candidate, cleminorexton (formerly referred to as ORX750), is a novel, oral, highly potent and selective orexin receptor 2 (OX2R) agonist in late-stage clinical development for the treatment of central disorders of hypersomnolence, including narcolepsy type 1 (NT1), narcolepsy type 2 (NT2) and idiopathic hypersomnia (IH). We believe cleminorexton has best-in-class potential across all three indications, and first-in-class potential in NT2 and IH.

Supported by differentiated pharmacology, strong orexin biology, compelling translational and clinical rationale, and insights from the clinical development of cleminorexton, we are also advancing ORX142 and ORX489, our follow-up OX2R agonist candidates, for broader neuroscience indications within neurodegenerative and neuropsychiatric disorders. Our earlier stage pipeline consists of additional OX2R agonists and research efforts on differentiated pharmacology associated with activation of the orexin pathway.

The Proposed Lilly Transaction

On March 31, 2026, we entered into a Transaction Agreement (the “Transaction Agreement”) with Eli Lilly and Company, an Indiana corporation (“Lilly” or “Parent”), and LDH XV Corporation, a Delaware corporation, and direct wholly owned subsidiary of Parent (“Purchaser”), pursuant to which Purchaser (and/or at Parent’s election its nominee(s)), will acquire our entire issued and to be issued share capital (including shares represented by our ADSs) pursuant to a court-sanctioned scheme of arrangement under Part 26 of the UK Companies Act 2006 (the “Scheme of Arrangement” and such acquisition, the “Transaction”), for $38.00 in cash per share, without interest, plus one non-transferable contingent value right entitling the holders to receive up to three contingent cash payments of up to an aggregate of $9.00 per share, contingent upon the achievement of specified milestones set forth in the Contingent Value Rights Agreement (the “CVR Agreement”), substantially in the form attached as Annex I to the Transaction Agreement (such contingent value rights, the “CVRs” and, together with the Cash Consideration, the “Transaction Consideration”). The Transaction is expected to close in the third quarter of 2026, subject to certain customary closing conditions, including the approval of the Scheme of Arrangement by our shareholders, the sanction of the Scheme of Arrangement by the High Court of Justice of England and Wales and receipt of the required regulatory approvals. See “Note 12 – Subsequent events” to our audited consolidated financial statements included elsewhere in this Form 10-K for additional information regarding the Transaction.

Orexin Pathway

The orexin pathway (also known as the hypocretin system) is an important and well-validated target in neuroscience. The pathway is a vital neuromodulatory network originating in the hypothalamus. Orexin neurons project from the hypothalamus into multiple brain regions and release orexin (also known as hypocretin). Orexin is a key signaling neuropeptide that activates an array of downstream neurotransmitters and is implicated in numerous physiologic functions, including wakefulness, attention, cognition and mood. The orexin system consists of two orexin neuropeptides, orexin-A (OXA) and orexin-B (OXB) (also known as hypocretin-1 and hypocretin-2) which bind to and activate the orexin receptors, Orexin Receptor-1 (OX1R) and Orexin Receptor-2 (OX2R) on other neurons. These receptors are G protein-coupled receptors (GPCRs) and are abundantly expressed throughout the brain with different distribution patterns, suggesting they have distinct physiological roles acting through different neuronal pathways. Importantly, OXA and OXB

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both bind to OX2R with high affinity. Activation of OX1R and OX2R promotes calcium mobilization and membrane depolarization of target neurons, triggering the release of wake-promoting neurotransmitters including histamine, serotonin, acetylcholine, and dopamine and regulating wakefulness. OX2R has also been implicated in metabolism, behavioral arousal, mood and cognitive function consistent with its wide distribution in the brain.

Figure 1: Orexin Pathway

Sources: Pizza, F et al., J Sleep Res 2022;31(4):e13665; Toor, B et al., Front Neurol Neurosci 2021;45:38 ; Ten-Blanco, M et al., Front Neuroendo 2023;69:101066; and, Yamamoto, H et al., PLoS One, 2022;17(7):e0271901.

We believe OX2R agonists are potentially transformative therapeutics to address the pathophysiology of central disorders of hypersomnolence, including NT1, NT2 and IH, acting as an upstream intervention that activates multiple downstream pathways essential for promoting wakefulness. For NT1 specifically, OX2R agonists have the potential to address the underlying disease pathology, with the potential to re-activate orexin receptors which remain in the brain in postsynaptic neurons even after the loss of the natural orexin peptide, to reduce excessive daytime sleepiness (EDS), cataplexy, and other common symptoms of NT1. In NT2 and IH, where there are normal orexin levels, OX2R agonists have the potential to increase orexin receptor activation to reduce EDS and other common symptoms of these conditions. In addition, given the overlap of orexin pathways onto neural circuitry governing motor function, mood, attention, and cognition, we anticipate that OX2R agonists may also have broad applicability in treating impaired attention, mood, cognitive deficits, fatigue and other symptoms across other neuroscience indications.

Our Orexin Franchise

Our wholly owned orexin franchise includes multiple small-molecule novel OX2R agonists with different chemical composition and pharmacokinetic (PK) profiles to support first- and best-in-class potential across targeted neuroscience indications, alongside research efforts on differentiated pharmacology associated with the activation of the orexin pathway.

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Figure 2: Pipeline

Although OX2R agonism has long been recognized as having significant therapeutic potential, there has been a substantial gap in the development of OX2R agonists primarily as a result of the challenge in designing small molecule drugs that target the OX2R receptor. The development of a small molecule orexin agonist requires highly complex medicinal chemistry to address a number of key challenges including the design of a brain penetrant molecule with a highly potent and selective chemical structure that can mimic the precise binding and activating properties of the native peptide, which is approximately seven-fold larger in size than the average small molecule CNS drug. As a result, OX2R has historically been considered a difficult-to-drug target, and development of an effective OX2R agonist therapeutic has been significantly limited.

Our team possesses a deep understanding of the orexin pathway and has extensive capabilities across key areas of research and development with a significant focus on translational medicine, computational and structural biology, and medicinal chemistry. Through a collaboration with Nxera, we gained exclusive access to a stabilized OX2R G protein-coupled receptor (“GPCR”) protein, known as StaR, which enabled the determination of three-dimensional structures of the OX2R bound to novel orexin agonists via X-ray crystallography, Cryo-EM and Biophysical Mapping. Leveraging this proprietary structure-based drug design and our medicinal chemistry capabilities, we have overcome historic OX2R agonist development challenges.

We have discovered and are advancing multiple novel OX2R agonist candidates designed to mimic the natural neuropeptide orexin with different PK profiles. These candidates have demonstrated robust activity in preclinical efficacy models and high selectivity for OX2R. These targeted profiles, which also include duration of action and rapid onset of action among others, are intended to support first- and best-in-class potential of our OX2R agonist across selected indications.

Figure 3: Clinical stage OX2R agonist product candidate profiles

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Sources: 1. Black et al., World Sleep 2023 Abstract., 2. Black et al., European Sleep Research Society 2024 Abstract. 3. Company data / presentations.

Cleminorexton: Our Lead Clinical Program for NT1, NT2 and IH

Program Overview

Cleminorexton is a potential best-in-class investigational, oral, highly selective and potent OX2R agonist in development for the treatment of NT1, NT2 and IH with first-in-class potential in NT2 and IH.

Phase 2a CRYSTAL-1 Study in Patients with NT1, NT2 and IH

The ongoing CRYSTAL-1 study is an adaptive, randomized, double-blind, placebo-controlled study of cleminorexton in patients with NT1, NT2 and IH. The goals of the study are to demonstrate the safety and tolerability of cleminorexton, evaluate PK and pharmacodynamic (PD) measures, and identify the optimal dose(s) and regimen of cleminorexton in each indication for the ongoing registrational program. For initial dose cohorts, independent cohorts with NT1, NT2, and IH participants received both cleminorexton and placebo treatment (administered once daily) randomized in a 2-week crossover design. Efficacy was assessed by the change from baseline in mean sleep latency (MSL) on the Maintenance of Wakefulness Test (MWT), and excessive daytime sleepiness on the Epworth Sleepiness Scale (ESS), each compared with placebo, and, for NT1 participants, by the incidence rate ratio for Weekly Cataplexy Rate (WCR) compared with placebo. After completion of each indication cohort, a new dose was selected and reviewed by the Safety Review Committee based on observed safety, tolerability, exposure and efficacy.

Following the initial dose cohorts, the study was adapted to a 4-week parallel design. Under this design, participants in ongoing and future cohorts are randomized to one of two blinded treatment sequences and receive 4 weeks of treatment with either cleminorexton or placebo (administered either once-daily or as a split dose) followed by a 2-week crossover to the other treatment. Efficacy is assessed after the initial 4-week parallel treatment period. Following completion of CRYSTAL-1, participants may enroll into an ongoing open-label long term extension (LTE) study of cleminorexton with separate cohorts for each condition.

2-Week Crossover Data Update:

In November 2025, we shared preliminary topline data from the completed initial dosing cohorts of cleminorexton within CRYSTAL’s 2-week crossover design for NT1, NT2 and IH (n=55) as of a September 23, 2025 data cutoff date. As of that cutoff date, cleminorexton was observed to be generally well-tolerated at all doses tested across each indication with all TEAEs being transient and mild to moderate in severity. One participant discontinued from treatment due to urinary urgency in the NT2 cohort. There were no clinically meaningful changes in cardiac, visual, liver or renal function. The most common TEAEs (≥10%) across all completed NT1, NT2 and IH cohorts were pollakiuria (51%), insomnia (22%), dizziness (13%) and headache (11%).

In NT1 participants, statistically significant, clinically meaningful and dose-dependent improvements from baseline compared with placebo were observed in mean sleep latency on the MWT and ESS scores in the 1.0 mg and 1.5 mg dose cohorts of cleminorexton administered once daily. More specifically, in the 1.5 mg cohort (n=6), cleminorexton achieved a >20-minute change from baseline in mean sleep latency compared with placebo on the MWT at Week 2 (p-value =0.0026), with half the participants achieving >30 minutes in mean sleep latency on the MWT. Also, in the 1.5 mg cohort (n=7), participants had a mean ESS total score of 5.1 with cleminorexton compared to a mean ESS total score of

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18.7 with placebo at Week 2 (p-value =0.0001). Participants had a mean ESS total score of 19.6 at baseline. Cleminorexton also achieved statistically significant, clinically meaningful and dose-dependent reductions in Weekly Cataplexy Rate (WCR) at both doses. In the 1.5 mg cohort (n=7), participants with cleminorexton had an 87% relative reduction in WCR compared with placebo, with an estimated incidence rate ratio of 0.13 at Week 2 (p-value = 0.0025).

In NT2 participants, statistically significant, clinically meaningful and dose-dependent improvements from baseline compared with placebo were observed in mean sleep latency on the MWT and ESS scores in the 2.0 mg and 4.0 mg dose cohorts of cleminorexton administered once daily. More specifically, in the 4.0 mg cohort (n=10), cleminorexton achieved a >10-minute change from baseline in mean sleep latency compared with placebo on the MWT at Week 2 (p-value = 0.0193). Also, in the 4.0 mg cohort (n=10), participants had a mean ESS total score of 8.1 with cleminorexton compared to a mean ESS total score of 15.9 with placebo at Week 2 (p-value =0.0023). Participants had a mean ESS total score of 17.3 at baseline.

In IH participants, statistically significant and clinically meaningful improvements from baseline compared with placebo were observed on multiple efficacy measures including mean sleep latency on the MWT (p-value =0.0213) in the 2.0 mg dose cohort (n=17) administered once daily.

CRYSTAL-1 is ongoing.

Phase 1 Study in Healthy Volunteers

In May 2024, we announced the initiation of a Phase 1 first-in-human (FIH) clinical study of cleminorexton in healthy volunteers. The Phase 1 study is a randomized, double-blind, sponsor-open, placebo-controlled, study evaluating the safety, tolerability, PK, and PD of cleminorexton in healthy adult participants. This study incorporates a standard SAD/MAD study design, various food effect evaluations, and a PoC phase designed to demonstrate the potential efficacy of cleminorexton versus placebo following crossover dose administration in acutely sleep-deprived healthy male participants to establish a preliminary exposure-response relationship. We previously shared data from PoC cohorts that evaluated single doses of cleminorexton at 1.0, 2.5, 3.5, and 5.0 mg. The mean sleep latency on the MWT showed dose-dependent improvements and a full range of response across the evaluated doses, with the 5.0 mg dose producing MWT scores approaching the limit of the test. The Phase 1 study is ongoing and as of a January 14, 2026 data cutoff date, over 254 participants have been dosed with cleminorexton at doses administered with once-daily and split-dosing regimens which have enabled ongoing and planned future dose escalation in the Phase 2a study. The adverse event profile observed in the Phase 1 study has remained generally consistent with previously reported Phase 1 data.

Narcolepsy (NT1 and NT2) and Idiopathic Hypersomnia (IH)

Narcolepsy is a rare, lifelong, debilitating neurological disorder that affects the brain’s ability to regulate the normal sleep-wake cycle, resulting in EDS, among other symptoms. Narcolepsy symptoms usually start during adolescence or early adulthood, between 7-25 years of age, and diagnostic delays of 8-12 years are common. Narcolepsy is estimated to affect approximately 126,000 to 175,000 people in the United States (US), and over three million people worldwide; however, there are several different estimates of the size of the population based on different epidemiological methods, and calculations likely underestimate the size of the population due to diagnostic challenges. It is estimated that less than 50% of affected patients are diagnosed.

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Financial statements

data from SEC XBRL filings. Values are as-reported; restatements supersede originals. Values reported in .

From 10-Q filed 2026-05-05 (period ending 2026-03-31).

Item 2. Management’s Discussion and Analysis of Financial Condition and Results of Operations

The following discussion and analysis should be read in conjunction with the unaudited interim consolidated financial statements and related notes thereto, included elsewhere herein and the audited consolidated financial statements and notes thereto for the year ended December 31, 2025 and the related Management’s Discussion and Analysis of Financial Condition and Results of Operation, all of which are contained in our Annual Report on Form 10-K (the “2025 Annual Report”) filed with the SEC. In addition to historical financial information, some of the information contained in the following discussion and analysis contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. All statements other than statements of historical facts, including statements regarding our future results of operations and financial position, business strategy, current and prospective products, product approvals, research and development costs, current and prospective collaborations, timing and likelihood of success, plans and objectives of management for future operations and future results of current and anticipated products, are forward-looking statements. These statements involve known and unknown risks, uncertainties, assumptions and other important factors that may cause our actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements.

Overview

We are a clinical-stage biotechnology company pioneering a new class of therapeutics in orexin-based neuroscience. We are developing a franchise of small molecule orexin receptor 2 (OX2R) agonists designed to address neuroscience diseases underpinned by dysregulation of wakefulness, attention, cognition, mood, and other symptoms, each grounded in the shared biology of the orexin pathway. Our OX2R agonist pipeline includes cleminorexton (formerly referred to as ORX750), our most advanced OX2R agonist development candidate, ORX142, ORX489, and other OX2R agonists in preclinical development, and research efforts on differentiated pharmacology associated with the activation of the orexin system. We also have an early-stage immuno-oncology program focused on our novel LockBody® technology platform.

We own worldwide rights to all of our pipeline programs and may opportunistically evaluate and enter into strategic partnerships around certain product candidates, targets, geographies, or disease areas.

The Proposed Lilly Transaction

Liquidity and Capital Resources

As of March 31, 2026, we had cash, cash equivalents and investments of $533.7 million. Since inception, we have devoted substantially all of our resources to acquiring and developing product and technology rights, conducting research and development in its discovery and enabling stages, advancing clinical and preclinical trials, business operations and raising capital. We have incurred recurring losses and negative cash flows from operations since inception and have funded operations primarily through the sale and issuance of our equity securities and debt financing. The ability to generate product revenue sufficient to achieve profitability will depend heavily on the successful development and eventual commercialization of current or future product candidates. We expect to continue to incur significant expenses and operating losses for the foreseeable future in connection with ongoing development activities related to our pipeline programs as we advance the preclinical and clinical development of product candidates; perform research activities as we seek to discover and develop additional programs and product candidates; carry out maintenance, expansion enforcement, defense, and protection of our intellectual property portfolio; and hire additional research and development, clinical and commercial personnel. Further, inflation may affect our use of capital resources by increasing our cost of labor, research, manufacturing and clinical trial expenses. Based on our

current operating model and development plans, we expect cash, cash equivalents and investments as of March 31, 2026 of $533.7 million to fund our operations into mid-2028.

Components of Results of Operations

Revenues

While we received non-recurring revenue related to out-licensing in the past, our ability to generate recurring product revenue and to become profitable will depend upon the ability to successfully develop, obtain regulatory approval and commercialize any current and future product candidates. Because of the numerous risks and uncertainties associated with product development and regulatory approval, we are unable to predict the amount or timing of product revenue.

Research and Development Expense

Research and development expenses consist primarily of costs incurred in connection with the discovery and development of the Company’s clinical and preclinical programs, net of reimbursements. Research and development costs are expensed as incurred. These expenses include:

•expenses incurred to conduct the necessary preclinical studies and clinical trials required to obtain regulatory approval;

•milestone payments pursuant to the license agreements;

•personnel expenses, including salaries, benefits and share-based compensation expense for employees engaged in research and development functions;

•costs of funding research and development performed by third parties, including pursuant to agreements with contract research organizations (“CROs”) for active and discontinued programs, as well as investigative sites and consultants that conduct preclinical studies and clinical trials;

•expenses incurred under agreements with contract manufacturing organizations (“CMOs”), including committed costs for discontinued programs, manufacturing scale-up expenses and the cost of acquiring and manufacturing preclinical study and clinical trial materials;

•fees paid to consultants who assist with research and development activities;

•expenses related to regulatory activities, including filing fees paid to regulatory agencies; and

•allocated expenses for facility costs, including rent, utilities, depreciation and maintenance.

Research and development activities are central to our business model. Product candidates in later stages of clinical development will generally have higher development costs than those in earlier stages of clinical development, primarily due to the increased size and duration of later-stage clinical trials. We expect research and development expenses to increase significantly over the next several years due to increases in costs to conduct clinical trials for current product candidates and other clinical trials for future product candidates and costs to prepare regulatory filings for any product candidates and increases in personnel costs, including share-based compensation.

The successful development of our current or future product candidates is highly uncertain. At this time, we cannot reasonably estimate or know the nature, timing and costs of the efforts that will be necessary to complete the remainder of the development of current or future product candidates, or when, if ever, material net cash inflows may commence from product candidates. This uncertainty is due to the numerous risks and uncertainties associated with the duration and cost of clinical trials, which vary significantly over the life of a project as a result of many factors, including:

•delays in regulators or institutional review boards authorizing us or our investigators to commence our clinical trials, or in our ability to negotiate agreements with clinical trial sites or CROs;

•the ability to secure adequate supply of product candidates for trials;

•the number of clinical sites included in the trials;

•the ability and the length of time required to enroll suitable patients;

•the number of patients that ultimately participate and remain in the trials;

•the number of doses patients receive;

•any side effects associated with product candidates;

•the duration of patient follow-up;

•the results of clinical trials;

•significant and changing government regulations; and

•launching commercial sales of product candidates, if and when approved, whether alone or in collaboration with others.

Our expenditures are subject to additional uncertainties, including the terms and timing of regulatory approvals. We may never succeed in achieving regulatory approval for our product candidates.

We may obtain unexpected results from clinical trials and may elect to discontinue, delay or modify clinical trials of product candidates. A change in the outcome of any of these variables with respect to the development of a product candidate could mean a significant change in the costs and timing associated with the development of that product candidate. For example, if the European Medicines Agency ("EMA"), FDA or other comparable regulatory authorities were to require us to conduct clinical trials beyond those that are currently anticipated, or if we experience significant delays in enrollment in any clinical trials, we could be required to expend significant additional financial resources and time on the completion of clinical development. Product commercialization will take several years, and we expect to spend a significant amount in development costs.

Research and Development Tax Incentives

We participate in research tax incentive programs that are granted to companies by the United Kingdom in order to encourage technical and scientific research. Expenditures that meet the required criteria are eligible to receive a tax benefit. Estimates of the amount of the benefit expected to be received are determined at each reporting period and recorded as reductions to research and development expenses. Through December 31, 2024, we claimed relief under the Small and Medium Enterprise (“SME”) scheme. Beginning January 1, 2025, changes to the program in the UK have aligned the tax incentives earned for SME and large entities. The merged scheme provides relief for qualifying R&D expenditure. If we are loss making, a cash payment can be obtained. If we continue to meet the SME thresholds and are loss making, then a higher rate of credit or payment may be available under the new Enhanced R&D Intensive Support (ERIS). We expect eligible R&D expenditures qualifying for the credit outside of the UK will be more limited as a result of these legislative changes and we expect to recognize less R&D tax incentive payments in the United Kingdom.

General and Administrative Expense

General and administrative expense consists primarily of personnel expenses, including salaries and benefits for employees and share-based compensation. General and administrative expense also includes facility costs, including rent, utilities, depreciation and maintenance, not otherwise included in research and development expense, as well as legal fees related to intellectual property and corporate matters and fees for accounting, consulting and other professional services.

Interest and Investment Income and Interest Expense

Interest and Investment income is primarily interest earned from the Company’s cash and cash equivalents and its investments and realized gains on sales of securities. Interest expense consists of interest costs related to the Loan and Security Agreement.

Other Non-Operating Income (Expense), net

Other non-operating income (expense), net consists primarily of foreign currency transaction gains and losses.

Foreign Currency Translation

Our financial statements are presented in U.S. dollars ("USD"), the reporting currency of the Company. The functional currency of Centessa Pharmaceuticals plc is USD and the functional currency of its subsidiaries is their respective local currency. Income and expenses have been translated into USD at average exchange rates prevailing during the period. Assets and liabilities have been translated at the rates of exchange on the balance sheets dates and equity accounts at their respective historical rates. The resulting translation gain and loss adjustments are recorded directly as a separate component of

shareholders’ equity as other comprehensive income (loss). Transactions denominated in a currency other than the functional currency are remeasured based upon the exchange rate at the date of remeasurement with the resulting gain or loss included in the accompanying unaudited interim consolidated statements of operations and comprehensive loss within other non-operating income (expense), net.

Results of Operations

The following table sets forth the results of operations for the three months ended March 31, 2026 and March 31, 2025 (amounts in thousands):

	Three Months Ended March 31, 2026		Three Months Ended March 31, 2025
License and other revenue	$	—	$	15,000
Operating expenses:
Research and development	59,891		33,443
General and administrative	19,882		12,334
Loss from operations	(79,773)		(30,777)
Interest and investment income	5,138		7,890
Interest expense	(2,731)		(2,877)
Other non-operating income (expense), net	(1,025)		1,026
Loss before income tax expense	(78,391)		(24,738)
Income tax expense	850		1,397
Net loss	$	(79,241)	$	(26,135)

License and other revenue

On February 14, 2025, the Company entered into a license agreement (the “License Agreement”) with Genmab A/S (“Genmab”). During the three months ended March 31, 2025, the Company recorded revenue of $15.0 million related to a $15.0 million up front payment received from Genmab upon execution of the License Agreement. See Note 4 - Genmab License Agreement.

Research and Development Expenses

The following table summarizes research and development expenses by program incurred for the following periods (amounts in thousands):

	Three Months Ended March 31, 2026		Three Months Ended March 31, 2025
Programs:
Cleminorexton1	$	20,503	$	13,666
Other Orexin program expenses1	23,758		6,427
LockBody technology program expenses	1,530		3,418
Discontinued programs	(52)		2,917
Non-asset specific costs:
Personnel expenses	15,799		10,459
Research tax incentives	(3,630)		(4,259)
Other internal R&D expenses	1,983		815
Research and development expenses	$	59,891	$	33,443
1 Beginning December 31, 2025, expenses related to the cleminorexton trial have been identified as significant segment expenses. The expenses for this trial have been recast for periods prior to December 31, 2025. These amounts were previously combined and disclosed under “OX2R agonist” for the quarter ended March 31, 2025.

Research and development expenses for the three months ended March 31, 2026 were $59.9 million, compared with $33.4 million for the three months ended March 31, 2025. The increase in research and development expenses reflects higher development costs of $24.2 million for the Orexin program and higher personnel expenses. Specifically, the cleminorexton program increased $6.8 million due to higher clinical study costs associated with the LTE clinical trial, which was initiated in the second half of 2025. Other Orexin program expenses increased by $17.3 million due to higher clinical study costs for ORX142 as well as developmental milestones related to ORX489. Personnel expenses in the first three months of 2026 increased $5.3 million primarily driven by increased headcount and higher salaries from annual merit increases and higher fringe benefit costs.

General and Administrative Expenses

The following table summarizes the general and administrative expenses for the following periods (amounts in thousands):

	Three Months Ended March 31, 2026		Three Months Ended March 31, 2025
Personnel expenses	$	11,514	$	7,033
Legal and professional fees	5,540		2,980
Other expenses	2,828		2,321
	$	19,882	$	12,334

General and administrative expenses for the three months ended March 31, 2026 were $19.9 million, compared to $12.3 million for the three months ended March 31, 2025. This was primarily driven by a $4.5 million increase in personnel costs, primarily due to $2.7 million of non-cash share-based payment expense incurred due to modifications of certain options and RSUs during the three months ended March 31, 2026, as well as $1.7 million in higher salaries from annual merit increases and higher fringe benefit costs. The increase was further driven by a $2.6 million increase in Legal and professional fees, primarily due to $2.5 million in advisory fees incurred in the quarter related to the proposed Lilly Transaction.

Interest and Investment Income and Interest Expense

For the three months ended March 31, 2026, interest and investment income was $5.1 million, which was a decrease of $2.5 million compared to the three months ended March 31, 2025, resulting from lower investment income offset by higher interest earned from the Company’s fixed investments due to a higher average cash, cash equivalent and investments balance as compared to the prior quarter.

Interest expense was $2.7 million in the first three months of 2026, reflecting a decrease of $0.2 million from the first three months of 2025, as a result of a lower interest rate.

Other Non-Operating Income (Expense), net

Other non-operating income (expense), net for the three months ended March 31, 2026 was a loss of $1.0 million, compared to a gain of $1.0 million three months ended March 31, 2025, with the change resulting from foreign currency fluctuations during each period.

Liquidity and Capital Resources

Sources of Liquidity

As of March 31, 2026, we had cash, cash equivalents and investments of $533.7 million, of which $62.4 million was classified as cash and cash equivalents, $214.2 million was classified as short-term investments and $257.1 million was classified as long-term investments on our Consolidated Balance Sheet. The Company invests in money market funds, U.S. Treasury securities, U.S. government agency securities, corporate notes and commercial paper. The Company’s investment policy limits investments to money market funds, certain types of debt securities issued by the U.S. Government and its agencies, corporate notes and commercial paper, and places restrictions on the credit ratings, maturities and concentration by type and issuer. Securities with original maturities of three months or less when purchased are included in cash and cash equivalents. We consider investments with original maturities greater than three months and remaining maturities less than one year to be short-term investments, while remaining maturities greater than one year are classified as long-term investments.

Based on our current operating model and development plans, we expect cash, cash equivalents and investments as of March 31, 2026 to fund our operations into mid-2028.

On December 30, 2024, the Company entered into a loan and security agreement (the “Loan and Security Agreement”) with Oxford Finance LLC (“Oxford”), as collateral agent and a lender, and the other lenders from time to time party thereto (collectively, the “Lenders”), pursuant to which the Lenders have agreed to lend the Company an aggregate principal amount of up to $200.0 million in a series of term loans (the “Term Loans”).

Pursuant to the Loan and Security Agreement, the Company received $110.0 million (the “Initial Term Loan”) and incurred $1.1 million of debt issuance costs inclusive of facility and legal fees. The Company has access to up to an additional $40.0 million of loan proceeds in an additional tranche which is available during the period commencing on the date of the occurrence of the Clinical Milestone (as defined in the Loan and Security Agreement) through the earlier of: (i) 90 days following the Clinical Milestone and (ii) June 30, 2028. An additional $50.0 million may be made available to the Company at the Lenders’ sole discretion.

The term loans are set to mature on December 1, 2029 and, following an interest-only period, will begin to amortize in equal monthly installments beginning on February 1, 2029. However, if the Extension Event as defined in the Agreement occurs, then at the Company’s option, the term loans could begin to amortize in equal monthly installments beginning on February 1, 2030, and the maturity date will be extended to December 1, 2030.

On September 11, 2024, we filed an automatic shelf registration statement on Form S-3ASR (“Shelf”) registering an unspecified amount of our ordinary shares, American Depository Shares representing ordinary shares, debt securities, warrants, and/or units or any combination thereof with the SEC under the Securities Act. The Shelf automatically became effective upon filing. Under the Shelf, we may offer securities from time to time in one or more offerings, at prices and on terms to be determined by market conditions at the time of offering. The specifics of any future offerings, along with the use of proceeds of any securities offered, will be described in detail in a prospectus supplement, or other offering materials, at the time of any offering.

The Company entered into a Sales Agreement, dated January 27, 2023 and amended and restated on November 24, 2025 (the “Sales Agreement”), by and between Centessa Pharmaceuticals plc and Leerink Partners LLC. As sales agent, Leerink Partners LLC provided for the issuance and sale by the Company of up to $250.0 million of its ordinary shares represented by American Depository Shares (“ADSs”) from time to time in “at-the-market” offerings (“ATM Program”). In the three months ended March 31, 2026, the Company has not sold any ordinary shares under the ATM Program. Since the inception of the ATM program in 2023, as of March 31, 2026, the Company sold 4,663,354 ordinary shares under the ATM Program, resulting in net proceeds of approximately $36.6 million under the Sales Agreement.

In 2025, the Company completed offerings of its ordinary shares through the sale and issuance of a cumulative 13,372,093 ADSs. Each ADS represents one ordinary share with a nominal value of £0.002 per ordinary share. The completed offerings, which included the Underwriters’ over-allotment option to purchase additional shares, were made pursuant to the Shelf registration. The net proceeds of these offerings, after deducting underwriting discounts and commissions and offering expenses, was approximately $269.2 million. The Company intends to use the net proceeds from the offerings, together with its existing cash, cash equivalents, and investments, to fund the continued development of its product candidates, as well as for general corporate purposes.

We have no other ongoing material financing commitments, such as lines of credit or guarantees, that are expected to affect liquidity over the next five years.

Cash Flows

The following table shows a summary of cash flows for the periods indicated (amounts in thousands):

	Three Months Ended March 31, 2026		Three Months Ended March 31, 2025
Net cash (used in) provided by:
Operating activities	$	(72,224)	$	(57,246)
Investing activities	42,707		(222,388)
Financing activities	30,467		3,086
Exchange rate effect on cash and cash equivalents	182		(1,517)
Net increase (decrease) in cash and cash equivalents	$	1,132	$	(278,065)

Operating Activities

During the three months ended March 31, 2026, we used $72.2 million of net cash in operating activities. Cash used in operating activities reflected a net loss of $79.2 million reduced by non-cash charges of $12.8 million, which included share-based compensation, depreciation and amortization expenses. In addition, cash used in operating activities during the three months ended March 31, 2026 included net outflows of approximately $5.8 million related to decreases in accrued expenses and other liabilities and tax incentive receivables.

During the three months ended March 31, 2025, we used $57.2 million of net cash in operating activities. Cash used in operating activities reflected a net loss of $26.1 million reduced by non-cash charges of $6.3 million, which included share-based compensation, depreciation and amortization expenses. In addition, cash used in operating activities during the three months ended March 31, 2025 included net outflows of approximately $38.5 million related to paying down net payables during the period, including $25.0 million related to the program terminations costs accrued in the fourth quarter of 2024.

Investing Activities

During the three months ended March 31, 2026, net cash provided by investing activities was $42.7 million, largely reflecting proceeds from redemption of fixed income investments. During the three months ended March 31, 2025, net cash used in investing activities was $222.4 million, largely reflecting the net investment of excess cash in fixed income investments.

Financing Activities

During the three months ended March 31, 2026, net cash provided by financing activities was $30.5 million, primarily reflecting the proceeds from stock option exercises, offset by payment of employee withholding taxes related to share-based compensation. During the three months ended March 31, 2025, net cash provided by financing activities was $3.1 million, primarily reflecting the proceeds from the ATM program, partially offset by payment of employee withholding taxes related to share-based compensation.

Funding Requirements

In future years, we expect expenses to increase as we continue further development of our product candidates and ultimately seek marketing approval for any current and future product candidates. In addition, we will begin to incur pre-commercial preparatory activities and, if marketing approval is obtained for any product candidates, we expect to incur significant commercialization expenses related to product sales, marketing, manufacturing and distribution. In addition, inflation may affect our use of capital resources by increasing our cost of labor, research and clinical trial expenses. Accordingly, there will be a need to obtain substantial additional funding in connection with the continuing operations. If we

are unable to raise capital when needed or on attractive terms, we would be forced to delay, reduce or eliminate research and development programs or future commercialization efforts.

We anticipate that our expenses will increase substantially as we:

•seek to discover and develop current and future clinical and preclinical product candidates;

•scale up clinical and regulatory capabilities;

•adapt regulatory compliance efforts to incorporate requirements applicable to marketed products;

•establish a sales, marketing and distribution infrastructure and scale up external manufacturing capabilities to commercialize any product candidates for which regulatory approval may be obtained;

•maintain, expand and protect the intellectual property portfolio;

•hire additional internal or external clinical, manufacturing and scientific personnel or consultants;

•add operational, financial and management information systems and personnel, including personnel to support product development efforts; and

•incur additional legal, accounting and other expenses in operating as a public company.

Because of the numerous risks and uncertainties associated with the research, development and commercialization of product candidates, we are unable to estimate the exact amount of our working capital requirements. Future funding requirements will depend on and could increase significantly as a result of many factors, including:

•the scope, progress, results and costs of preclinical studies and clinical trials;

•the scope, prioritization and number of research and development programs;

•the costs, timing and outcome of regulatory review of product candidates;

•the ability to establish and maintain collaborations on favorable terms, if at all;

•the costs of preparing, filing and prosecuting patent applications, maintaining and enforcing intellectual property rights and defending intellectual property-related claims;

•the costs of securing manufacturing arrangements for commercial production; and

•the costs of establishing or contracting for sales and marketing capabilities if regulatory approvals are obtained to market product candidates.

Identifying potential product candidates and conducting preclinical studies and clinical trials is a time-consuming, expensive and uncertain process that takes many years to complete, and may never generate the necessary data or results required to obtain marketing approval and achieve product sales. In addition, product candidates, if approved, may not achieve commercial success. Commercial revenues, if any, will be derived from sales of product candidates that we do not expect to be commercially available for the next couple of years, if at all. Accordingly, we will need to continue to rely on additional financing to achieve our business objectives. Adequate additional financing may not be available on acceptable terms, or at all.

Critical Accounting Policies and Estimates

Our management’s discussion and analysis of our financial condition and results of operations is based on our consolidated financial statements, which have been prepared in accordance with generally accepted accounting principles in the United States. The preparation of these consolidated financial statements requires us to make estimates and assumptions that affect the reported amounts of assets and liabilities and the disclosure of contingent assets and liabilities at the date of the consolidated financial statements, as well as the reported expenses incurred during the reporting periods. Our estimates are based on our historical experience and on various other factors that we believe are reasonable under the circumstances, the results of which form the basis for making judgments about the carrying value of assets and liabilities that are not readily apparent from other sources. Actual results may differ from these estimates under different assumptions or conditions.

As of March 31, 2026, the Company’s critical accounting policies and estimates had not changed significantly from December 31, 2025. Note 2, “Summary of Significant Accounting Policies,” to the consolidated financial statements in our Annual Report on Form 10-K for the fiscal year ended December 31, 2025 describes the significant accounting policies and methods used in the preparation of the consolidated financial statements appearing in this Quarterly Report.

Contractual Obligations and Other Commitments

As of March 31, 2026, other than what has been disclosed in Note 7 – Debt and Note 8 – Commitment and contingencies, there were no material changes to our contractual obligations and other commitments described under “Management’s Discussion and Analysis of Financial Condition and Results of Operations” in our Annual Report on Form 10-K for the fiscal year ended December 31, 2025.

Emerging Growth Company and Smaller Reporting Company Status

The Company is an emerging growth company, as defined in the JOBS Act. Under the JOBS Act, emerging growth companies can delay the adoption of new or revised accounting standards issued subsequent to the enactment of the JOBS Act until such time as those standards apply to private companies. Other exemptions and reduced reporting requirements under the JOBS Act for emerging growth companies include presentation of only two years of audited financial statements in a registration statement for an initial public offering, an exemption from the requirement to provide an auditor’s report on internal controls over financial reporting pursuant to Section 404 of the Sarbanes-Oxley Act of 2002, as amended, an exemption from any requirement that may be adopted by the Public Company Accounting Oversight Board regarding mandatory audit firm rotation and less extensive disclosure about our executive compensation arrangements. The Company has elected to use the extended transition period for complying with new or revised accounting standards that have different effective dates for public and private companies until the earlier of the date that (i) it is no longer an emerging growth company or (ii) the Company affirmatively and irrevocably opts out of the extended transition period provided in the JOBS Act.

The Company will remain an emerging growth company until the earliest of (i) the last day of its first fiscal year in which it has total annual gross revenues of $1.235 billion or more, (ii) the last day of its first fiscal year following the fifth anniversary of the closing of its initial public offering, (iii) the date on which it is deemed to be a “large accelerated filer,” under the rules of the SEC, or (iv) the date on which we have issued more than $1.0 billion in non-convertible debt securities during the prior three-year period.

As of January 1, 2026, the Company ceased to be a “smaller reporting company” (“SRC”) as defined in the Exchange Act. For the first fiscal quarter of 2026, the Company is no longer permitted to take advantage of scaled disclosure requirements for SRCs. The Company will retain its non-accelerated filer status for its filings due in the fiscal year 2026. The Company anticipates that it will have to comply with the auditor attestation requirements of Section 404(b) of the Sarbanes-Oxley Act for the year ended December 31, 2026, and its independent registered public accounting firm will have to evaluate and report on the effectiveness of internal control over financial reporting.

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Holder	Type	ETF	MF	Position ($)	% of holder	Δ % of holder	Holder AUM

Next expected filings

~2026-11-05 10-Q expected by 2026-11-07 (in 53 days)
~2027-03-30 10-K expected by 2027-03-31 (in 198 days)
~2027-05-05 10-Q expected by 2027-05-07 (in 234 days)
~2027-08-12 10-Q expected by 2027-08-14 (in 333 days)

Predicted from historical filing cadence; not an SEC commitment.

Recent SEC filings

2026-06-24 8-K Material Agreement Terminated; Completion of Acquisition/Disposition; Delisting Notice; Material Modification to Rights; Control Change; Officer/Director Change; Other Events; Financial Statements and Exhibits
2026-06-12 8-K Shareholder Vote Results; Other Events
2026-05-22 8-K Other Events
2026-05-05 10-Q Quarterly Report
2026-04-17 PREM14A PREM14A
2026-03-31 10-K Annual Report
2026-03-31 8-K Material Agreement Entered; Regulation FD Disclosure; Financial Statements and Exhibits
2026-02-13 8-K Officer/Director Change
2026-01-07 8-K/A Officer/Director Change; Financial Statements and Exhibits
2025-12-11 8-K Officer/Director Change; Regulation FD Disclosure; Financial Statements and Exhibits
2025-11-24 8-K Other Events; Financial Statements and Exhibits
2025-11-13 8-K Material Agreement Entered; Other Events; Financial Statements and Exhibits
2025-11-05 10-Q Quarterly Report
2025-11-05 8-K Earnings Release; Regulation FD Disclosure; Financial Statements and Exhibits
2025-08-12 10-Q Quarterly Report

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