Aankondiging • Jul 06
Centessa Pharmaceuticals plc Files Form 15 Centessa Pharmaceuticals plc has announced that it has filed a Form 15 with the Securities and Exchange Commission to voluntarily deregister its Ordinary Shares, nominal value 0.002 per share and American Depositary Shares, each representing one ordinary share under the Securities Exchange Act of 1934, as amended. Aankondiging • Jun 26
Centessa Pharmaceuticals plc(NasdaqGM:CNTA) dropped from NASDAQ Composite Index Centessa Pharmaceuticals plc has been dropped from the NASDAQ Composite Index Board Change • May 20
Insufficient new directors There is 1 new director who has joined the board in the last 3 years. The company's board is composed of: 1 new director. 7 experienced directors. No highly experienced directors. CEO & Director Mario Accardi was the last director to join the board, commencing their role in 2026. The company’s insufficient board refreshment is considered a risk according to the Simply Wall St Risk Model. Aankondiging • May 04
Centessa Pharmaceuticals plc, Annual General Meeting, Jun 12, 2026 Centessa Pharmaceuticals plc, Annual General Meeting, Jun 12, 2026. Location: sancroft, 10-15 newgate street, ec1a 7az, london United Kingdom Aankondiging • Mar 31
Eli Lilly and Company (NYSE:LLY) entered into a definitive agreement to acquire Centessa Pharmaceuticals plc (NasdaqGS:CNTA) from Medicxi Ventures (UK) LLP, Index Ventures SA, General Atlantic Service Company, L.P. and other shareholders for $5.6 billion. Eli Lilly and Company (NYSE:LLY) entered into a definitive agreement to acquire Centessa Pharmaceuticals plc (NasdaqGS:CNTA) from Medicxi Ventures (UK) LLP, Index Ventures SA, General Atlantic Service Company, L.P. and other shareholders for $5.6 billion on March 31, 2026. Under the terms of the transaction agreement, Eli Lilly will acquire all of the issued and to be issued share capital of Centessa (including the American Depositary Shares (ADSs) representing ordinary shares) for $38.00 in cash per share plus one non-transferrable contingent value right (CVR) that entitles the holder to receive up to an aggregate of $9.00 subject to the achievement of three milestones described below, for total potential aggregate per share consideration of up to $47.00. CVR holders would become entitled to receive contingent payments as follows: (i) $2.00 per CVR in cash, upon U.S. FDA approval of cleminorexton (formerly ORX750) or ORX142 for the treatment of narcolepsy type 2 prior to the fifth anniversary of transaction closing; (ii) $5.00 per CVR in cash, upon U.S. FDA approval of cleminorexton (formerly ORX750) or ORX142 for the treatment of idiopathic hypersomnia prior to the fifth anniversary of transaction closing; and (iii) $2.00 per CVR in cash, upon the first U.S. FDA approval of cleminorexton (formerly ORX750) or ORX142 for the treatment of any indication prior to January 1, 2030. The agreement stipulates a $63.06 million termination fee payable by the target to the buyer.
Entities affiliated with Medicxi Ventures, entities affiliated with Index Ventures, and affiliates of General Atlantic have signed voting and support agreements whereby they agree to vote to approve the transaction. The shares subject to the agreements represent a total of approximately 24.1% of Centessa’s outstanding ordinary shares (represented by ADSs). The transaction, which will be effectuated by way of a scheme of arrangement under the laws of England and Wales, subject to approval by Centessa shareholders, sanction by the High Court of Justice of England and Wales and satisfaction of other customary closing conditions, including regulatory and antitrust approvals. The boards of directors of both companies have approved the transaction. The transaction is expected to close in the third quarter of 2026.
Morgan Stanley & Co. LLC acted as financial advisor for Eli Lilly and Company. Sarkis Jebejian, Keri Schick Norton, Steven M. Choi of Kirkland & Ellis LLP and Dipak Bhundia, Bonian Wu of Kirkland & Ellis International LLP acted as legal advisor for Eli Lilly and Company. Centerview Partners LLC and Jefferies LLC acted as financial advisors for Centessa Pharmaceuticals plc. Stuart M Cable, Lisa R Haddad, Blake Liggio of Goodwin Procter LLP acted as legal advisor for Centessa Pharmaceuticals plc. Aankondiging • Jun 18
Centessa Pharmaceuticals plc Announces Clearance of Investigational New Drug Application for ORX142 Centessa Pharmaceuticals plc announced that the U.S. Food and Drug Administration (FDA) has cleared the IND to initiate a Phase 1 clinical study of ORX142 in healthy volunteers. ORX142 is an investigational, novel, highly potent and selective OX2R agonist being developed for the treatment of select neurological and neurodegenerative disorders. ORX142 is the second drug candidate from the Company’s multi-asset orexin franchise. The Phase 1 study will evaluate the safety, tolerability and pharmacokinetics of single-ascending doses (SAD) and multiple-ascending doses (MAD) of ORX142 in healthy volunteers. In parallel to the SAD, a placebo-controlled crossover pharmacodynamic (PD) assessment will be performed utilizing the Maintenance of Wakefulness Test (MWT) and Karolinska Sleepiness Scale (KSS) in acutely sleep-deprived healthy adult subjects. The Company plans to initiate the first-in-human Phase 1 clinical study imminently, with clinical data expected 2025. Aankondiging • Apr 23
Centessa Pharmaceuticals plc, Annual General Meeting, Jun 20, 2025 Centessa Pharmaceuticals plc, Annual General Meeting, Jun 20, 2025. Location: offices of goodwin procter (uk) llp at sancroft, 10-15 newgate street, london, ec1a 7az, United Kingdom Aankondiging • Jan 08
Centessa Pharmaceuticals Announces Appointment of Stephen Kanes as Chief Medical Officer Centessa Pharmaceuticals plc announced the appointment of Stephen Kanes MD PhD, as Chief Medical Officer (CMO). Dr. Kanes is a neuropsychiatrist, with a career in neuroscience, clinical psychiatry, and neuroscience drug development spanning more than 30 years. Dr. Kanes served as Chief Medical Officer of Sage Therapeutics from 2013 to 2021, where he led the successful clinical development of ZULRESSO® (brexanolone), the first-ever treatment approved for Postpartum Depression (PPD), along with the buildout of the development organization and Sage Therapeutics' broad neuroscience portfolio. Most recently, Dr. Kanes was Chief Executive Officer of EmbarkNeuro, a neuroscience focused biotech company. Earlier in his career, Dr. Kanes was Executive Director in Clinical Development in the Inflammation, Neuroscience and Respiratory therapeutic areas at AstraZeneca, and a faculty member of the University of Pennsylvania Department of Psychiatry where he explored both the genetics and physiology of severe mental illness. He has authored or co-authored more than 60 peer-reviewed publications in behavioral neuroscience, behavioral pharmacology, genetics, brain imaging, clinical trials, and health economics and serves as an ad hoc reviewer for multiple journals including Neuropsychopharmacology andThe American Journal of Medical Genetics and Biological Psychiatry. Dr. Kanes received his BA from the University of Pennsylvania in the Biological Basis of Behavior and both his PhD in Molecular and Cellular Pharmacology and MD from the Stony Brook University Renaissance School of Medicine. He completed his psychiatry residency at Yale-New Haven Medical Center and a neuropsychiatry postdoctoral fellowship at the University of Pennsylvania. Aankondiging • Nov 13
Centessa Pharmaceuticals Initiates Phase 2 Trial with ORX750, a Novel Orexin Receptor 2 (OX2R) Agonist Nxera Pharma Co. Ltd. announced that Centessa Pharmaceuticals has initiated a Phase 2 trial of ORX750, an investigational, orally administered, highly potent and selective orexin receptor 2 (OX2R) antagonist for the treatment of narcolepsy type 1 (NT1), narcolepsy type 2 (NT2), and idiopathic hypersomnia. The achievement of this milestone results in a payment of USD 3.5 million to Nxera pursuant to its research collaboration with Centessa. This will be recognised as revenue in Fourth Quarter Fiscal Year 2024. ORX750 was designed using Nxera technology to directly target the underlying pathophysiology of orexin neuron loss in NT1, with potential applicability to NT2, idiopathic hypersomnia, and other sleep- wake disorders with normal orexin levels. Recent Insider Transactions • Oct 25
CEO & Director recently sold €801k worth of stock On the 23rd of October, Saurabh Saha sold around 55k shares on-market at roughly €14.57 per share. This transaction amounted to 16% of their direct individual holding at the time of the trade. This was the largest sale by an insider in the last 3 months. This was Saurabh's only on-market trade for the last 12 months. Recent Insider Transactions • Sep 30
Chief Business Officer recently sold €234k worth of stock On the 25th of September, Gregory Weinhoff sold around 17k shares on-market at roughly €14.06 per share. This transaction amounted to 19% of their direct individual holding at the time of the trade. This was the largest sale by an insider in the last 3 months. This was the only on-market transaction from insiders over the last 12 months. Aankondiging • Sep 12
Centessa Pharmaceuticals plc has filed a Follow-on Equity Offering in the amount of $150 million. Centessa Pharmaceuticals plc has filed a Follow-on Equity Offering in the amount of $150 million.
Security Name: American Depositary Shares
Security Type: Depositary Receipt (Common Stock) Aankondiging • Sep 10
Centessa Pharmaceuticals plc Announces Positive Interim Phase 1 Clinical Data with Its Novel Orexin Receptor 2 (OX2R) Agonist, Orx750, in Acutely Sleep-Deprived Healthy Volunteers Centessa Pharmaceuticals plc announced positive interim data from an ongoing Phase 1 trial of its highly potent and selective orexin receptor 2 (OX2R) agonist, ORX750, in acutely sleep-deprived healthy volunteers. ORX750 showed clinically meaningful and statistically significant improvements in mean sleep latency at the first two doses evaluated (1.0 mg and 2.5 mg) in the Maintenance of Wakefulness Test (MWT) compared to placebo. More specifically, the 2.5 mg dose was shown to restore normative wakefulness2 with a mean sleep latency of 32 minutes as measured by the MWT. ORX750 was also shown to have a favorable safety and tolerability profile with no observations of frequently reported on-target adverse events (AEs) associated with other OX2R agonists, and no cases of hepatotoxicity or visual disturbances across all three dose levels tested (1.0 mg, 2.0 mg, and 2.5 mg), as of the data cutoff date.1 Based on the interim data, the Company plans to rapidly advance ORX750 into Phase 2 studies in patients with narcolepsy type 1 (NT1), narcolepsy type 2 (NT2), and idiopathic hypersomnia (IH) beginning in the fourth quarter of 2024. The Phase 1 clinical study is an ongoing first-in-human, randomized, placebo-controlled study designed to evaluate the safety, tolerability and pharmacokinetics (PK) of single-ascending doses (SAD) and multiple-ascending doses (MAD) of ORX750 in healthy adult subjects. In parallel to the SAD, a placebo-controlled cross-over pharmacodynamic (PD) assessment is being performed utilizing the MWT and Karolinska Sleepiness Scale (KSS) in acutely sleep-deprived healthy adult subjects with the goal of rapidly generating early efficacy data to inform dosing for planned studies in patients. As of September 10, 2024, the study has completed three SAD cohorts of healthy volunteers (27 active, 9 placebo) with doses of 1.0 mg, 2.0 mg, and 2.5 mg, and has advanced through two cohorts within the cross-over assessment of acutely sleep-deprived healthy volunteers with doses of 1.0 mg (n=8) and 2.5 mg (n=8), administered as a single oral dose. Dosing in the MAD portion of the study is also ongoing. Board Change • Jun 02
Insufficient new directors There is 1 new director who has joined the board in the last 3 years. The company's board is composed of: 1 new director. 7 experienced directors. No highly experienced directors. Independent Non-Executive Director Mathias Hukkelhoven was the last director to join the board, commencing their role in 2022. The company’s insufficient board refreshment is considered a risk according to the Simply Wall St Risk Model. Aankondiging • Apr 23
Centessa Pharmaceuticals plc Announces Open IND for ORX750 Centessa Pharmaceuticals plc announced that the U.S. Food and Drug Administration (FDA) has cleared the Investigational New Drug application (IND) to initiate a Phase 1 first-in-human, clinical trial of ORX750 for the treatment of narcolepsy. ORX750 is an investigational, orally administered, highly potent and selective orexin receptor 2 (OX2R) agonist designed to directly target the underlying pathophysiology of orexin neuron loss in narcolepsy type 1 (NT1), with potential applicability to narcolepsy type 2 (NT2), idiopathic hypersomnia (IH), and other sleep-wake disorders with normal orexin levels. The Phase 1 study will evaluate the safety, tolerability and pharmacokinetics of single-ascending doses (SAD) and multiple-ascending doses (MAD) of ORX750 in healthy adult subjects. In parallel to the SAD, a cross-over pharmacodynamic (PD) assessment will be performed utilizing the Maintenance of Wakefulness Test (MWT) and Karolinska Sleepiness Scale (KSS) in acutely sleep-deprived healthy adult subjects which is intended to provide proof-of-concept data to enable dose selection for NT1, NT2 and IH indications. The study has a maximum exposure limit specified by the FDA which the Company believes significantly exceeds the predicted efficacious doses of ORX750 in indications associated with or without orexin loss; therefore, the Company does not expect this limit to affect any of the planned clinical development activities for ORX750. The Company expects to commence dosing of the Phase 1 study in healthy volunteers imminently, and proof-of-concept data are anticipated in the second half of 2024. ORX750 is an investigational, orally administered, highly potent and selective orexin receptor 2 (OX2R) agonist designed to directly target the underlying pathophysiology of orexin neuron loss in narcolepsy type 1 (NT1). ORX750 has been shown to potently activate the OX2R with an in vitro EC50 of 0.11 nM and 9,800-fold selectivity over the human orexin receptor (hOX1R). ORX750 is Centessa’s first orexin product candidate being developed for the treatment of narcolepsy with potential expansion into narcolepsy type 2 (NT2), idiopathic hypersomnia (IH) and other sleep-wake disorders. New Risk • Mar 29
New major risk - Revenue and earnings growth Earnings are forecast to decline by an average of 0.5% per year for the foreseeable future. This is considered a major risk. Ultimately, shareholders want to see a good return on their investment and that generally comes from sharing in the company's profits. If profits are expected to decline, then in most cases the share price will decline over time as well. In addition, if the company pays dividends it will also likely need to reduce or cut them, striking a dual blow to total shareholder returns. Currently, the following risks have been identified for the company: Major Risks Share price has been highly volatile over the past 3 months (12% average weekly change). Earnings are forecast to decline by an average of 0.5% per year for the foreseeable future. Revenue is less than US$1m. Minor Risks Currently unprofitable and not forecast to become profitable over next 3 years (US$222m net loss in 3 years). Shareholders have been diluted in the past year (3.2% increase in shares outstanding). New Risk • Mar 05
New major risk - Revenue and earnings growth Earnings are forecast to decline by an average of 0.3% per year for the foreseeable future. This is considered a major risk. Ultimately, shareholders want to see a good return on their investment and that generally comes from sharing in the company's profits. If profits are expected to decline, then in most cases the share price will decline over time as well. In addition, if the company pays dividends it will also likely need to reduce or cut them, striking a dual blow to total shareholder returns. Currently, the following risks have been identified for the company: Major Risks Share price has been highly volatile over the past 3 months (12% average weekly change). Earnings are forecast to decline by an average of 0.3% per year for the foreseeable future. Revenue is less than US$1m. Minor Risks Currently unprofitable and not forecast to become profitable over next 3 years (US$218m net loss in 3 years). Shareholders have been diluted in the past year (3.2% increase in shares outstanding). Aankondiging • Dec 11
Centessa Pharmaceuticals plc Announces New Data from an Additional 52-Weeks of Continuous Treatment from Third Year (Part 5) of Ongoing Phase 2A Study of Serpinpc for the Treatment of Hemophilia Centessa Pharmaceuticals plc announced new data from an additional 52-we weeks of continuous treatment from the third year (Part 5) of the ongoing Phase 2a study of SerpinPC for the treatment of hemophilia. The data were shared in a poster presentation at the American Society of Hematology (ASH) Annual Meeting on December 10, 2023. During treatment with SerpinPC all breakthrough bleeds were treated on-demand w ith usual clotting factor concentrate, without dose reduction and without limitation of number of infusions. Data from Part 5 were presented at the ASH Annual Meeting in a poster titled: SerpinPC in persons with severe hemophilia (PwH): Updated results from a multi-center, multi-part, first-in-human study. Aankondiging • Nov 01
Centessa Pharmaceuticals plc Announces Dosing of First Subject in Registrational Present-3 Study Evaluating Serpinpc for the Treatment of Hemophilia B with Inhibitors Centessa Pharmaceuticals plc announced the dosing of the first subject in its registrational Present-3 study of SerpinPC for the treatment of hemophilia B with inhibitors. The dosing phase of Present-3 follows a minimum 12-week observation period during which prospective baseline data of the subject's disease status under their current therapy are collected to support regulatory review of the benefit and risk profile of SerpinPC. SerpinPC is a 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 U.S. Food and Drug Administration (FDA) has granted Fast Track designation to SerpinPC for the treatmentof hemophilia B, with or without inhibitors. SerpinPC is an investigational agent that has not been approved by the FDA or any other regulatory authority. Aankondiging • Oct 26
Centessa Pharmaceuticals plc Announces Preclinical Data Supporting Orx750's Potential as A Best-In-Class Oral Ox2r Agonist for the Treatment of Narcolepsy and Other Sleep-Wake Disorders Centessa Pharmaceuticals plc announced a robust set of new preclinical data from in vivo and in vitro studies of its investigational, novel orexin receptor 2 (OX2R) agonist, ORX750, that support its potential best-in-class profile for the treatment of narcolepsy and other sleep- wake disorders. ORX750 is an investigational, orally administered, highly potent and selective orexin receptor 2 (ox2R) agonist designed to directly target the underlying pathophysiology of orexin neuron loss in narcolepsy type 1 (NT1). ORX750 is Centessa's first orexin product candidate being developed for the treatment of narcolpsy with potential expansion into other sleep- wake disorders.ORX750 is currently undergoing IND-enabling activities and has not been administered as an investigational drug to humans in any jurisdiction. Any such statements that are not statements of historical fact may be deemed to be forward-looking statements, including statements related to: the Company's ability to deliver transformational medicines to patients; the activity significance of low doses in highly predictive, translational models of narcolepsy type 1 ("NT1") including maximal wake times and suppressed cataplexy at the lowest oral dose tested; the Company's expectations on the timing of Ind-enabling studies of ORX750 in narcolepsy and other Sleep- wake disorders; the ability of management team and board to drive execution of the Company's portfolio of programs; asset-centric business model and the intended advantages and benefits thereof; the scope, progress, results and costs of developing product candidates or any other future product candidates; current expectations concerning, amongst other things, the development and therapeutic potential and benefits of product candidates, including ORX750 and other OX2R agonists; strategy; regulatory matters, including the timing and likelihood of initiating clinical trials, reporting clinical trial results, ability to initiate or continue clinical trials or market any products; and the market size and opportunity for product candidates. Based on current expectations, estimates 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 out 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 product candidates including ORX750; ability to protect and maintain 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; ability to obtain adequate financing, including through financing facility with Oberland, to fund 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; future expenditures risks related to asset-centric corporate model; the risk that any one or more of product candidates will not be successfully developed and/or commercialized; and the risk that the results of non-clinical studies or clinical studies will not be predictive of future results. Aankondiging • Aug 25
World Sleep Congress Releases an Abstract Submit by Centessa Pharmaceuticals plc On August 22, 2023, the World Sleep Congress 2023 released an abstract submitted by Centessa Pharmaceuticals Plc. containing preclinical data on ORX750, the company's orally administered, selective orexin receptor 2 (OX2R) agonist in development for the treatment of narcolepsy and other sleep disorders. The company will present the abstract in an oral presentation on October 25, 2023. Introduction: Narcolepsy Type 1 (NT1) is a rare neurological disease caused by the profound loss of orexin-producing neurons. Orexin (also called hypocretin) is a neurotransmitter that regulates wakefulness, arousal, and energy homeostasis via activation of Orexin Receptor-1 (OX1R) and -2 (OX2R). Orexin agonists are designed to directly address the underlying disease pathology of NT1 to restore orexin neurotransmission in the brain. The orexin/ataxin-3 (Atax) mouse model of NT1 recapitulates key features of the human disorder, such as orexin loss, inability to sustain wakefulness, and cataplexy (emotionally triggered, transient loss of muscle tone). Here it present ORX750, a novel, orally available, brain penetrant, OX2R selective agonist. ORX750 was developed using structure-based drug design with an OX2R stabilized receptor (StaR®) protein and high-resolution protein crystallography. Materials and Methods: In vitro calcium mobilization (FLIPR), ß-arrestin recruitment, and inositol-phosphate accumulation assays were performed in Chinese hamster ovary (CHO) cells stably expressing human recombinant OX1R or OX2R. Electrophysiological recordings were performed on slices of the ventral tuberomammillary nucleus (TMN) from mouse hypothalamus; effects on membrane potential were measured in the presence of 1 micromolar tetrodotoxin to block neuron firing. In vivo efficacy for enhancing wakefulness was evaluated in wild type (WT) and Atax mice during their rest phase using PiezoSleep, a rapid, non-invasive method for classifying sleep and wakefulness by unsupervised machine learning on physiologically relevant readouts, including body movement and breath rate. Electroencephalogram (EEG), electromyogram (EMG), and video recordings were used in Atax mice during their active phase to evaluate effects at 0.3-10 mg/kg on arousal states and cataplexy. Results: ORX750 behaved as a potent full agonist at human OX2R (EC50=0.11 nM) relative to the native ligand orexin A (OXA; EC50=0.035 nM) and showed 9,800-fold selectivity over human OX1R (EC50=1100 nM) in the FLIPR assay. Biased agonism was not detected by measurement of b-arrestin recruitment at OX2R in comparison to OXA. ORX750 depolarized membrane potential (EC50=5.0 nM, max DmV=9.5) in whole cell current-clamp recordings in the TMN. In the PiezoSleep assay, in which wakefulness readouts are highly correlated with EEG/EMG-defined wakefulness, ORX750 increased time awake and the consolidation of wakefulness vs. vehicle in a dose-related manner when administered to WT and Atax mice during the rest phase. Increased sensitivity to these wake-promoting effects was observed in Atax vs. WT mice. In Atax mice, ORX750 increased time awake; consolidated wakefulness; increased EEG gamma power during wakefulness; reduced cataplexy occurrences; and increased latencies to sleep and cataplexy in a dose-related manner during the active phase using the EEG/EMG/video assay. At the lowest dose tested (0.3 mg/kg) and compared to vehicle, the latency to sleep was 2.3 h vs. 0.69 h and the latency to cataplexy was 2.7 h vs. 1.3 h. Conclusions: ORX750 is an oral, highly potent, and selective OX2R agonist with the potential to treat patients with primary symptoms of NT1, as well as reduce excessive sleepiness in those presenting sleep/wake disorders with normal orexin levels. New Risk • Aug 15
New major risk - Revenue and earnings growth Earnings are forecast to decline by an average of 3.1% per year for the foreseeable future. This is considered a major risk. Ultimately, shareholders want to see a good return on their investment and that generally comes from sharing in the company's profits. If profits are expected to decline, then in most cases the share price will decline over time as well. In addition, if the company pays dividends it will also likely need to reduce or cut them, striking a dual blow to total shareholder returns. Currently, the following risks have been identified for the company: Major Risks Share price has been highly volatile over the past 3 months (13% average weekly change). Earnings are forecast to decline by an average of 3.1% per year for the foreseeable future. Revenue is less than US$1m. Minor Risks Currently unprofitable and not forecast to become profitable over next 3 years (US$239m net loss in 3 years). Shareholders have been diluted in the past year (3.2% increase in shares outstanding). Aankondiging • Jul 12
Centessa Pharmaceuticals Announces Dosing of First Subject in Registrational PRESent-2 Study Evaluating SerpinPC for the Treatment of Hemophilia B Without Inhibitors Centessa Pharmaceuticals plc announced the dosing of the first subject in its registrational PRESent-2 study of SerpinPC for the treatment of hemophilia B without inhibitors. The dosing phase of PRESent-2 follows a minimum 12-week observation period during which prospective baseline data of the subject’s disease status under their current therapy are collected to support regulatory review of the benefit and risk profile of SerpinPC. SerpinPC is an investigational subcutaneously administered novel inhibitor of activated protein C (APC) being developed as a potential treatment for hemophilia B, with or without inhibitors. The PRESent-2 study (AP-0102) is a Phase 2b, global, open-label, seamless adaptive design study to investigate the efficacy and safety of subcutaneous dosing of SerpinPC every week, every 2 weeks, or every 4 weeks in approximately 120 adult (aged 18 to =65 years) or adolescent (aged =12 to <18 years) male subjects with severe hemophilia A (with or without inhibitors) or moderately severe to severe hemophilia B (without inhibitors). PRESent-2 consists of 3 parts: a 24-week randomized dose-justification phase (Part 1), a 24-week dose-confirmatory phase (Part 2), and a further 24-week extension phase (Part 3) for subjects who complete either Part 1 or Part 2. Subjects must have undergone a minimum period of prospective observation (at least 12 weeks for Part 1 or 24 weeks for Part 2) under their current therapy (either on-demand or prophylaxis factor replacement) before switching to SerpinPC treatment. The primary efficacy endpoint for the study is the rate of treated bleeds (expressed as an annualized bleeding rate (ABR)) in the observation period compared to the first 24 weeks treated with SerpinPC. The Company expects to begin dosing in its registrational PRESent-3 (AP-0103) study for subjects with hemophilia B with inhibitors this year. New Risk • Jul 06
New major risk - Share price stability The company's share price has been highly volatile over the past 3 months. It is more volatile than 90% of German stocks, typically moving 9.8% a week. This is considered a major risk. Share price volatility increases the risk of potential losses in the short-term as the stock tends to have larger drops in price more frequently than other stocks. It may also indicate the stock is highly sensitive to market conditions or economic conditions rather than being sensitive to its own business performance, which may also be inconsistent. Currently, the following risks have been identified for the company: Major Risks Share price has been highly volatile over the past 3 months (9.8% average weekly change). Revenue is less than US$1m. Minor Risk Currently unprofitable and not forecast to become profitable over next 3 years (US$235m net loss in 3 years). Aankondiging • May 23
Centessa Pharmaceuticals Receives Fast Track Designation from the U.S. FDA for Serpinpc for Hemophilia B Centessa Pharmaceuticals plc announced that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation to SerpinPC, an investigational novel inhibitor of activated protein C (APC) being developed for the treatment of hemophilia B, with or without inhibitors. According to the FDA, Fast Track is a process designed to facilitate the development and expedite the review of drug candidates to treat serious conditions and fulfill an unmet medical need. A therapeutic candidate that receives Fast Track designation may be eligible for more frequent interactions with the FDA to discuss the candidate’s development plan and, if relevant criteria are met, eligibility for Accelerated Approval, Priority Review, or Rolling Review. Aankondiging • Jan 27
Centessa Pharmaceuticals Announces FDA Clearance of IND Application for Phase 1/2a Clinical Trial of LB101, First LockBody® Candidate, for Solid Tumors Centessa Pharmaceuticals plc announced that it has received clearance of its Investigational New Drug (IND) application from the U.S. Food and Drug Administration (FDA) to initiate a Phase 1/2a first-in-human, clinical trial of LB101 for the treatment of solid tumors. LB101, a conditionally tetravalent PD-L1xCD47 LockBody® bispecific monoclonal antibody targeting solid tumors, is the first product candidate developed using the Company’s proprietary LockBody technology which is designed to selectively drive potent effector function activity, such as CD47, in the tumor microenvironment (TME) while avoiding systemic toxicity. Aankondiging • Dec 13
Centessa Pharmaceuticals plc Announces Additional 18-Months of Continued Treatment Data from Open-Label Extension of Phase 2a Study of SerpinPC for Hemophilia Centessa Pharmaceuticals plc announced new data from an additional 18-months of continued treatment with SerpinPC, an investigational, subcutaneously administered novel inhibitor of activated protein C (APC), from the open-label extension (OLE) of the Phase 2a study of SerpinPC for hemophilia. The OLE data show a continued favorable safety and tolerability profile for SerpinPC, including at a higher dosing regimen, as well as sustained long-term efficacy results, as measured by a reduction in the all-bleeds annualized bleed rates (ABRs). Consistent with data from the six-month repeat dose portion of the Phase 2a study, there were no thromboembolic events and no treatment-related sustained elevations of D-dimer observed throughout the 18-month OLE period reported on today. D-dimer is a sensitive measure of excess thrombin generation. In addition, there were no SerpinPC-related adverse events during the OLE period. Phase 2a Study and OLE: AP-0101 is an ongoing first-in-human open-label multi-center study to investigate the safety, tolerability, pharmacokinetics, and efficacy of subcutaneous doses of SerpinPC in male participants with severe hemophilia. Initial Study Period (Part 1 and Part 2): Part 1a was a Single Ascending Dose (SAD) study completed in 15 healthy male subjects and Part 1b was a SAD study completed in 12 male subjects with hemophilia A or B (Part 1b: 0.1 to 1.2 mg/kg, 4 cohorts). All 12 subjects in Part 1b chose to participate in Part 2. Part 2 enrolled a total of 23 male subjects with hemophilia who were not on replacement factor prophylaxis to receive SerpinPC at 0.3, 0.6 or 1.2 mg/kg, administered as a subcutaneous injection once every 4 weeks over a 24-week period (6 total doses). As previously disclosed, one subject with a history of a skin disorder discontinued treatment due to an injection site reaction during Part 2. No other SerpinPC-related adverse events were observed during the study. The Company announced the results for Part 2 (six month repeat dose) on September 9, 2021. After Part 2, participants were offered to continue into an open-label extension (OLE) of the Phase 2a study. OLE Period (Part 3 and Part 4): In Part 3, 22 subjects who completed Part 2 (six month repeat dose) received a flat dose of 60 mg of SerpinPC administered as a subcutaneous injection once every 4 weeks for 48 weeks. One subject emigrated out of the site country and discontinued treatment during Part 3. In Part 4, 21 subjects who completed Part 3 received 1.2 mg/kg of SerpinPC administered as a subcutaneous injection once every 2 weeks for 24 weeks. One subject discontinued treatment during Part 4 following a cancer diagnosis which the Safety Review Group determined was not related to treatment with SerpinPC. Phase 2a OLE Data from Additional 18-Months of Continued Treatment: SerpinPC was well-tolerated throughout the OLE’s 18-month treatment period. There were no SerpinPC-related adverse events and no thromboembolic events or treatment-related sustained elevations of D-dimer observed throughout the OLE period. There were no treatment-related discontinuations from the OLE. At the higher dose tested (Part 4: 1.2 mg/kg of SerpinPC administered as a subcutaneous injection once every 2 weeks for 24 weeks (n=21)), the median all-bleeds ABR was reduced by 93% as compared to the median all-bleeds ABR prospectively measured during the pre-exposure observation period. A median ABR of 2.2 was achieved for all subjects in Part 4. Seven subjects had zero bleeds during the 24-week period. The median spontaneous joint bleeds ABR was reduced by 93% as compared to the median spontaneous joint bleeds ABR prospectively measured during the pre-exposure observation period. A median spontaneous joint bleed ABR of 2.2 was achieved for all subjects in Part 4. Nine subjects had zero spontaneous joint bleeds during the 24-week period. All breakthrough bleed events during the OLE period were successfully managed with the subject’s usual replacement factor without dose adjustment and did not require adjustments to SerpinPC dosing. Aankondiging • Dec 01
Centessa Pharmaceuticals Announces Karen Anderson as New Chief People Officer Centessa Pharmaceuticals plc announced Karen Anderson as its new Chief People Officer. In this newly created position, Karen will lead the Company’s human resources function and help define Centessa’s people and culture strategy. Karen joins Centessa with over 25 years of experience in human resources roles spanning the biotechnology/pharmaceutical, technology and healthcare industries. Prior to joining Centessa, Karen was Chief Human Resources Officer at Mimecast Limited. Previously, she was Senior Vice President and Chief Human Resources Officer at Alnylam Pharmaceuticals where she supported the strategic direction and business growth from a few hundred employees to more than 1,000 employees in 16 global legal entities. Karen was also Vice President of Human Resources at Pfizer, supporting the Commercial business unit in both developed and emerging markets. Earlier in her career she was responsible for compensation, benefits and systems for Bayer Canada before becoming the Global Human Resources Director for Baxter where she had a strong focus on mergers and acquisitions. Board Change • Nov 16
High number of new and inexperienced directors There are 8 new directors who have joined the board in the last 3 years. The company's board is composed of: 8 new directors. No experienced directors. No highly experienced directors. Independent Chairman of the Board Francesco de Rubertis is the most experienced director on the board, commencing their role in 2020. The following issues are considered to be risks according to the Simply Wall St Risk Model: Lack of board continuity. Lack of experienced directors. Aankondiging • Nov 15
The Law Offices of Vincent Wong Announces Class Action Lawsuit Against Centessa Pharmaceuticals plc The Law Offices of Vincent Wong announced that a class action lawsuit has commenced on behalf of investors. This lawsuit is on behalf of a class consisting of persons and entities that purchased or otherwise acquired: (a) Centessa American Depositary Shares pursuant and/or traceable to documents issued in connection with the Company's initial public offering conducted on or about May 28, 2021; and/or (b) Centessa securities between May 28, 2021 and June 1, 2022. The class action against Centessa includes allegations that the Company made materially false and/or misleading statements and/or failed to disclose that: (i) the Company's product, lixivaptan, was less safe than defendants had represented; (ii) defendants overstated lixivaptan's clinical and commercial prospects; (iii) another Centessa product, ZF874, was less safe than defendants had represented; (iv) defendants overstated ZF874's clinical and commercial prospects while downplaying the drug's safety issues; and (v) as a result, documents issued in connection with Centessa's initial public offering and the Company's public statements throughout the class period were materially false and/or misleading and failed to state information required to be stated therein. Aggrieved Centessa investors only have until November 28, 2022 to request that the Court appoint as lead plaintiff. Aankondiging • Oct 15
Centessa Pharmaceuticals plc Announces Departure of Javad Shahidi as Chief Medical Officer Centessa Pharmaceuticals plc and Javad Shahidi, M.D., M.Sc., Chief Medical Officer, mutually agreed that Dr. Shahidi will be departing from the Company. Dr. Shahidi’s last day with the Company will be October 14, 2022. Dr. Shahidi’s departure was not the result of any disagreement regarding any matter relating to the Company’s operations, policies or practices. The Company thanks Dr. Shahidi for his contributions. Antoine Yver, M.D., M.Sc., Chairman of Development of the Company, will assume all responsibilities currently held by Dr. Shahidi effective October 14, 2022. Dr. Yver assumes these responsibilities with over 30 years of extensive global drug development and global program leadership experience in oncology and rare diseases, including deep expertise in regulatory affairs and policy. Dr. Yver has led the approvals for 11 different drugs, including Tagrisso, Lynparza, and Enhertu. Prior to joining Centessa in 2021, Dr. Yver was Executive Vice President and Global Head, R&D Oncology, and Chair of the Cancer Enterprise at Daiichi Sankyo Company Ltd. Previously, Dr. Yver was with AstraZeneca, PLC, most recently serving as Senior Vice President, Global Medicine Head, Oncology, and Global Medicines Development China Lead. Dr. Yver currently serves as an independent director on the Board of Sanofi and Spotlight Therapeutics. Aankondiging • Sep 30
Centessa Pharmaceuticals plc Announces Class Action Lawsuit Against Centessa Pharmaceuticals plc Johnson Fistel, LLP announced that a class action lawsuit has commenced on behalf of investors of Centessa Pharmaceuticals plc (Centessa or the Company). The class action is on behalf of shareholders who purchased or otherwise, acquired Centessa American Depository Shares (ADS) between May 28, 2021 and June 1, 2022 (the Class Period), including in, pursuant to, and/or traceable to the Company’s IPO. Investors are hereby notified that they have until November 28, 2022 to move the Court to serve as lead plaintiff in this action. Aankondiging • Sep 13
Centessa Pharmaceuticals Announces Non-Human Primate Pharmacokinetic and Safety Data for LB101 (PD-L1xCD47) Demonstrating Potential for Enhanced Therapeutic Index Centessa Pharmaceuticals plc announced non-clinical pharmacokinetic (PK) and safety data in non-human primates (NHPs) for LB101 (PD-L1xCD47), its first LockBody® candidate for solid tumors. Findings from these data reinforce the potential of its LockBody platform to minimize the systemic effects of potent immune effectors and significantly improve the therapeutic index. In the study, male and female cynomolgus monkeys were administered LB101 intravenously, every 7 days over 28 days (q7 days x 4) at doses of 5mg/kg, 20mg/kg, and 50mg/kg. The pharmacokinetics of LB101 were assessed and exhibited a typical IgG1-like PK profile. There were no adverse changes in hematologic parameters (including no anemia and no thrombocytopenia), no changes in body weights and no adverse toxicology findings. Aankondiging • Jul 26
Centessa Pharmaceuticals Announces Addition of Harris L. Rotman, Phd, as Senior Vice President of Regulatory Affairs Centessa Pharmaceuticals plc announced the appointment of Harris L. Rotman, PhD, as Senior Vice President, Regulatory Affairs. Prior to joining Centessa, Dr. Rotman served as Senior Vice President, Head of Regulatory Affairs at SwanBio Therapeutics, where he was responsible for managing the company’s neuromuscular disease gene therapy programs. Dr. Rotman also previously served as Vice President, Head of Regulatory Affairs, Branded Business at Endo Pharmaceuticals where he led the branded global regulatory affairs department in the US and Ireland. Earlier in his career, Dr. Rotman held executive regulatory leadership roles with Indivior, Shire Pharmaceuticals, Sanofi and Wyeth Pharmaceuticals. Dr. Rotman earned his PhD in Microbiology and Molecular Virology from Thomas Jefferson University, and a BS in Biological Sciences from Cook College at Rutgers University. Aankondiging • Jul 09
Centessa Pharmaceuticals plc Announces Executive Changes On July 1, 2022, Marella Thorell notified Centessa Pharmaceuticals plc of her decision to resign her position as the Company’s Chief Accounting Officer, and its principal accounting officer, effective as of July 31, 2022 to pursue another professional opportunity. Ms. Thorell’s resignation was not the result of a disagreement with the Company on any financial disclosures, accounting matters or any matter relating to the Company’s operations, policies or practices. Effective as of July 31, 2022, Gregory Weinhoff, M.D., M.B.A., the Company’s Chief Financial Officer, will assume the duties and responsibilities of the Company’s principal accounting officer, in addition to the Company’s principal financial officer. Dr. Weinhoff, age 51, has served as the company's Chief Financial Officer since March 2021. Previously, Dr. Weinhoff served as co-Founder, Chief Financial Officer and Chief Business Officer of Arvelle Therapeutics, B.V. from February 2019 to February 2021. Dr. Weinhoff also served as Chief Financial Officer of Axovant Sciences Inc. and Principal Financial Officer of Axovant Sciences Ltd. from August 2015 to June 2019 and the Principal Accounting Officer of Axovant Sciences Ltd. from June 2018 to June 2019. Dr. Weinhoff was employed by Collinson Howe Venture Partners, an investment advisory firm, from 2001 until August 2015 and during that time served as a Member of the General Partners of various CHL Medical Partners affiliated venture capital funds. From 2000 to 2001, he was a senior associate at J. H. Whitney & Co., a private equity firm, where he concentrated on private equity investments in healthcare technology and services companies. Prior to his graduate training, Dr. Weinhoff was a financial analyst in the Healthcare Corporate Finance Group at Morgan Stanley & Co., an investment bank. Dr. Weinhoff received his A.B. in economics from Harvard College, his M.D. from Harvard Medical School and his M.B.A. from Harvard Business School. Dr. Weinhoff has no family relationships with any of the executive officers or directors of the Company. There are no arrangements or understandings between Dr. Weinhoff and any other person pursuant to which he was elected as an officer of the Company. Aankondiging • Jul 02
Centessa Pharmaceuticals plc Announces Board Changes Centessa Pharmaceuticals plc announced the appointment of Mathias Hukkelhoven, Ph.D., formerly Senior Vice President, Global Regulatory, Safety & Biometrics at Bristol Myers Squibb (BMS), to its Board of Directors. In addition, the Company announced that Aaron Kantoff has resigned from the Company's Board, but will remain actively involved with the Company as an advisor. Both changes are effective July 1, 2022. Prior to joining BMS, Dr.Hukkelhoven held the role of Chairman Portfolio Stewardship Board at Novartis Pharmaceutics and served as the SeniorVice President, Global Head Drug Regulatory Affairs at Novartis from 2001 to 2009. He also worked at Hoffmann LaRoche(Switzerland) and Organon (The Netherlands). Dr. Hukkelhoven has served as chairperson of the Regulatory AffairsCoordinating Committee at PhRMA, and recently as a PhRMA negotiator for the PDUFA VII negotiations with the U.S. Foodand Drug Administration (FDA). Dr. Hukkelhoven received his BS and PhD with honors in Biology and Biochemistry from theUniversity of Nijmegen, the Netherlands. Dr. Hukkelhoven also serves on the Board of Directors of Compugen Ltd, and is aSenior Advisor to McKinsey and an R&D Strategy Advisor to LianBio. Aankondiging • Jun 06
Centessa Pharmaceuticals plc Announces Poster Presentation of First Preclinical Data for LockBody Program At 2022 ASCO Annual Meeting Centessa Pharmaceuticals plc announced presentation of the first preclinical data for LB101, PD-L1xCD47 LockBody, in a poster presentation at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting which is taking place virtually and in person from June 3-7, 2022 in Chicago, IL. The poster presentation will be featured in the Developmental Therapeutics – Immunotherapy session June 5, 2022, at 8-11 AM CT. The poster includes in vivo data in a MC38 hPD-L1+ syngeneic mouse model, which demonstrated significantly improved efficacy with durable responses for single-agent LB101 (26 of 32 tumors eradicated across two doses) compared to isotype control IgG (0 of 16) and atezolizumab (4 of 32 across two doses). In rechallenge experiments, none of the mice from groups with prior LB101-induced regressions exhibited tumor growth compared to all naïve mice which rapidly established tumors. At equimolar doses to atezolizumab, LB101 exhibited no anemia, weight-loss or overt toxicity. The poster also includes in vitro data, which demonstrated PD-L1 binding in the locked form and CD47 binding with strongly enhanced antibody-dependent cellular phagocytosis (ADCP) in the unlocked form. Aankondiging • Jun 03
Centessa Pharmaceuticals Makes Strategic Decision to Discontinue Clinical Development of Lixivaptan for Autosomal Dominant Polycystic Kidney Disease (ADPKD) Centessa Pharmaceuticals plc announced that it has made the strategic decision to discontinue development of lixivaptan for Autosomal Dominant Polycystic Kidney Disease (ADPKD) including both the Phase 3 ACTION Study and the open-label ALERT Study. The decision is based on a thorough reassessment of the commercial potential of lixivaptan as a potential best-in-class therapy for patients with ADPKD, and the incremental development challenges and associated costs, following a recent observation of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) elevations in one subject in the ALERT Study. Aankondiging • May 24
Centessa Pharmaceuticals plc, Annual General Meeting, Jun 30, 2022 Centessa Pharmaceuticals plc, Annual General Meeting, Jun 30, 2022, at 08:00 US Eastern Standard Time. Location: Goodwin Procter (UK) LLP, 100 Cheapside London United Kingdom Agenda: To consider Board changes; to appoint KPMG LLP, a United Kingdom entity, as U.K. statutory auditors of the Company, to hold office until the conclusion of the next meeting at which the Company’s annual accounts and reports are laid before the Company; to ratify the appointment of KPMG LLP, a Delaware limited liability partnership, as the Company’s independent registered public accounting firm, for the financial year ending December 31, 2022; to authorize the Audit Committee to determine the Company’s auditors’ remuneration for the financial year ending December 31, 2022; and to consider any other matter thereof. Board Change • Apr 27
High number of new and inexperienced directors There are 8 new directors who have joined the board in the last 3 years. The company's board is composed of: 8 new directors. No experienced directors. No highly experienced directors. Independent Chairman of the Board Francesco de Rubertis is the most experienced director on the board, commencing their role in 2020. The following issues are considered to be risks according to the Simply Wall St Risk Model: Lack of board continuity. Lack of experienced directors. Board Change • Apr 05
High number of new and inexperienced directors There are 8 new directors who have joined the board in the last 3 years. The company's board is composed of: 8 new directors. No experienced directors. No highly experienced directors. Independent Chairman of the Board Francesco de Rubertis is the most experienced director on the board, commencing their role in 2020. The following issues are considered to be risks according to the Simply Wall St Risk Model: Lack of board continuity. Lack of experienced directors. Aankondiging • Feb 25
Centessa Pharmaceuticals Doses First Subject in Global Phase 3 Action Study of Lixivaptan in Autosomal Dominant Polycystic Kidney Disease Centessa Pharmaceuticals plc announced it has started dosing of the first subject in its pivotal Phase 3 clinical trial evaluating lixivaptan as a potential treatment for Autosomal Dominant Polycystic Kidney Disease. The trial is expected to enroll approximately 1,350 subjects across more than 200 sites in over 20 countries. The Company anticipates completing enrollment in the second half of 2023 and, if results are supportive, plans to submit a New Drug Application after completion of the one-year double-blind portion of the study. Dosing of the first subject in the ACTION Study is the trigger for payment of the contingent value rights originally issued to former shareholders and option holders of Palladio in January 2021 in connection with Centessa’s acquisition of Palladio. The CVR will be settled in newly issued ADSs of Centessa. The ACTION Study is a Phase 3 trial consisting of a two-arm, double-blind, placebo-controlled, randomized phase followed by a single-arm, open-label phase. The ACTION Study will evaluate the efficacy and safety of lixivaptan that has been titrated to a maximum tolerated dose between 100-200 mg BID in subjects with ADPKD and a Mayo Clinic MRI imaging classification of 1C, 1D or 1E and an estimated glomerular filtration rate (“eGFR”) =25 and =90 mL/min/1.73 m2. The primary analysis of the ACTION Study will be performed at the end of Part 1 of the trial, which will have a 2:1 randomization and is designed to assess lixivaptan in slowing the decline in renal function as measured at 52 weeks by the difference in eGFR between the lixivaptan-treated and placebo-treated subjects. Final efficacy measurements at the end of the double-blind period will be conducted while subjects are off study drug during three clinic visits over a 28 day period. The trial is expected to enroll approximately 1,350 subjects across more than 200 sites in over 20 countries. All subjects successfully completing Part 1 are expected to continue into Part 2 of the study and will be treated with lixivaptan for an additional year to further assess the sustainability of the potential benefit on eGFR change over a two-year period. Consistent with Part 1, final efficacy measurements will be conducted off study drug. Both parts of the study will contribute to further evaluating the safety profile of lixivaptan. An independent data monitoring committee will periodically review all safety data, including the liver chemistry data for all subjects, throughout the study. The Company anticipates completing enrollment in the second half of 2023 and, if results are supportive, plans to submit an NDA after completion of the one-year double-blind portion of the study (“Part 1”). Aankondiging • Feb 17
Centessa Pharmaceuticals Limited Announces Resignation of Robert M. Califf as Member of the Board of Directors On February 16, 2022, Robert M. Califf, M.D., a member of the Board of Directors of Centessa Pharmaceuticals plc notified the Company of his resignation from the Board, effective immediately. Dr. Califf resigned as a result of his confirmation as the incoming Commissioner of the U.S. Food and Drug Administration. Dr. Califf’s resignation was not the result of a disagreement with the Company on any matter relating to the Company’s operations, policies or practices. Effective as of his resignation, Dr. Califf is no longer a member of the Board or any of its committees. Aankondiging • Dec 15
Centessa Pharmaceuticals plc Together with Subsidiary Palladio Biosciences, Inc. Initiates Global Phase 3 ACTION Study of Lixivaptan in Autosomal Dominant Polycystic Kidney Disease and Reports Initial Positive Safety Data from ALERT Study Centessa Pharmaceuticals plc together with subsidiary Palladio Biosciences, Inc. announced the initiation of active recruitment of the global ACTION Study, a pivotal Phase 3 clinical trial evaluating lixivaptan as a potential treatment for Autosomal Dominant Polycystic Kidney Disease (ADPKD). Additionally, the company reported initial safety data from four subjects who participated in the ongoing open-label ALERT Study of ADPKD subjects who previously discontinued JYNARQUE® (tolvaptan) due to liver toxicity and announced the Notice of Allowance for a U.S. Patent application covering use of lixivaptan in ADPKD. ACTION Study Initiation: recruitment has commenced in the global Phase 3 ACTION Study which consists of a two-arm, double-blind, placebo-controlled, randomized phase (Part 1) followed by a single-arm, open-label phase (Part 2). The study will evaluate the benefit and safety of lixivaptan that has been titrated to a maximum tolerated dose between 100-200 mg BID in subjects with ADPKD and a Mayo Clinic MRI imaging classification of 1C, 1D or 1E and an estimated glomerular filtration rate (eGFR) =25 and =90 mL/min/1.73 m2. The primary analysis of the ACTION Study will be performed at the end of Part 1 of the trial, which will have a 2:1 randomization (lixivaptan:placebo) and is designed to assess lixivaptan in slowing the decline in renal function as measured at 52 weeks by the difference in eGFR between the lixivaptan-treated and placebo-treated subjects. Final efficacy measurements at the end of the double-blind period will be conducted while the subject is off study drug over three successive clinic visits. The sample size of the study will be up to 1,350 subjects to provide 90% power to the primary analysis, aiming to detect a 1.4 mL/min/1.73 m2 eGFR difference between lixivaptan-treated and placebo-treated subjects. Thirteen clinical sites have been initiated and the trial is ultimately expected to enroll subjects across more than 200 sites in more than 20 countries. As previously disclosed, the company expects to dose the first subject in the ACTION Study by the first quarter of 2022. All subjects successfully completing Part 1 are expected to continue into Part 2 of the study and will be treated with lixivaptan for an additional 54-56 weeks to further assess the sustainability of the potential benefit on eGFR change over a two-year period. Consistent with Part 1, updated efficacy measurements will be conducted off study drug. Both parts of the study will contribute to further establishing the safety profile of lixivaptan. An independent data monitoring committee will periodically review all safety data including the liver chemistry data for all subjects throughout the study. The company anticipates completing enrollment in the second half of 2023 and, pending positive data, plans to submit a New Drug Application (NDA) after completion of the one-year double-blind portion of the study (Part 1). ALERT Study Update: the company also reported initial safety data from the ongoing open-label ALERT Study of ADPKD subjects who previously discontinued JYNARQUE® (tolvaptan) due to liver toxicity. The ALERT Study is designed to assess liver and non-liver safety in subjects who previously experienced liver chemistry test abnormalities that met the criteria for likely drug-induced liver injury (DILI) while being treated with tolvaptan and who permanently discontinued the drug. Subjects in the ALERT Study undergo up to 8 weeks of screening followed by a three-week baseline measurement period and then a three- to six-week titration phase with lixivaptan, with weekly liver chemistry test monitoring during the baseline and titration phases. During the maintenance phase, liver chemistry tests are obtained every four weeks. The primary outcome measure in the study is the proportion of subjects who develop alanine aminotransferase (ALT) levels >3x ULN adjudicated to be related to lixivaptan resulting in discontinuation of the study drug. To date, ten subjects have entered screening, five failed screening, and one failed the baseline measurement period. The four subjects who enrolled in the study had cases of DILI while being treated with tolvaptan for ADPKD and had ALT elevations that peaked between 1.8x and 3.5x ULN and did not return to below ULN until 23 to 140 days after tolvaptan use was discontinued. Each of these subjects was successfully titrated to a maintenance dose of lixivaptan of either 100 mg BID (one subject) or 200 mg BID (three subjects) and entered the maintenance phase of the study. As of the most recent data cutoff (December 3, 2021), three out of four subjects remain on lixivaptan with the longest treatment duration being 366 days, and the remaining subjects at 174 days and 172 days on treatment. One subject successfully titrated to 200 mg BID lixivaptan but withdrew consent after 93 days of dosing. No subjects have had clinically meaningful ALT elevations attributed to lixivaptan and no subjects met the pre-specified stopping criteria of an ALT level >3x ULN. The ALERT Study remains open for enrollment of subjects who have had a confirmed case of DILI while being treated with tolvaptan. Most subjects who stop treatment with tolvaptan due to liver toxicity are also eligible for enrollment in the ACTION Study, which is now the primary focus of the Company’s recruitment efforts. Aankondiging • Sep 10
Centessa Pharmaceuticals Announces Positive Topline Data from Proof-of-Concept Study of SerpinPC in Severe Hemophilia A and B Patients Not on Prophylaxis Centessa Pharmaceuticals plc together with subsidiary ApcinteX Limited announced positive topline results from the Phase 2a part of AP-0101, the six-month repeat dose portion of its ongoing first-in-human proof-of-concept study evaluating SerpinPC in severe hemophilia A and B patients. AP-0101 is a Phase 1/2a proof-of-concept study evaluating SerpinPC, an inhibitor of activated protein C, in 23 male subjects with either severe hemophilia A or B who were not on prophylaxis. The Phase 2a part of the study assessed the safety, tolerability and pharmacokinetics across three dose cohorts (0.3 mg/kg, 0.6 mg/kg and 1.2 mg/kg) of SerpinPC administered as a subcutaneous (SC) injection every 4 weeks over a 24-week period (6 total doses). Reduction in the annualized bleeding rates (ABRs) were exploratory outcomes. Although eligible, none of the patients in the study had inhibitors. SerpinPC was well-tolerated. As previously disclosed, one subject with a history of a skin disorder discontinued treatment on SerpinPC due to an injection site reaction. No other SerpinPC-related adverse events have been recorded. There was no reported sustained elevation in D-dimer, a sensitive measure of excess thrombin generation, throughout the 24-week study. Two subjects had anti-drug antibodies and remained on treatment without apparent impact on ABRs. 
