Safimaltib

关键词Loncastuximab tesirine；R/R DLBCL；研究进展日前，瓴路药业（上海）有限责任公司的「注射用Loncastuximab tesirine」被CDE拟纳入优先审评，用于治疗二线或多线系统治疗后复发或难治性大B细胞淋巴瘤成年患者。Loncastuximab tesirine（Lonca，商品名Zynlonta）是一款抗体偶联药物（ADC），由与CD19结合的人源化单克隆抗体与吡咯苯二氮平（PBD）二聚体毒素偶联构成。一旦与表达CD19的细胞结合，Lonca就会被细胞内化，随后释放出细胞毒素，该毒素能不可逆地与DNA结合，从而产生阻止DNA链分离的强力链间交联，从而破坏复制等必要的DNA代谢过程，最终导致细胞死亡。2021年4月，Lonca被FDA加速批准，单药治疗经过二线或以上全身系统性治疗的复发/难治性大B细胞淋巴瘤（R/R DLBCL）成人患者，成为FDA批准的首款CD19靶向ADC。据悉，在关键性注册临床试验LOTIS-2研究中，Lonca单药治疗既往接受过≥2次治疗的R/R DLBCL 的客观缓解率（ORR）为48.3%，完全缓解率（CR）为24.1%。此外，Lonca联合利妥昔单抗（即Lonca+R方案）针对DLBCL二线及以后且不符合移植条件的患者的确证性3期临床试验LOTIS-5正在进行中。已公布的临床试验数据显示：截止2022年2月28日，随访时间中位数为5.83个月，Lonca+R疗法的ORR为75%，CR为40%。值得一提的是，LOTIS-5试验是全球首个在R/R DLBCL二线治疗中利用ADC替代化疗方案的3期注册性临床试验。Lonca由ADC Therapeutics开发的。2020年，瓴路药业与ADC Therapeutics成立合资公司瓴路爱迪思（Overland ADCT BioPharma），负责在大中华区和新加坡开发和商业化包括Lonca在内的四款ADC。2023年4月，瓴路爱迪思宣布评价Lonca单药治疗复发/难治性弥漫大B细胞淋巴瘤（R/R DLBCL）中国患者的2期注册临床试验OL-ADCT-402-001达到主要研究目的。基于该研究结果，公司向NMPA递交上市申请。关于复发/难治性弥漫性大B细胞淋巴瘤弥漫性大B细胞淋巴瘤（DLBCL）是一种来源于成熟B细胞的侵袭性肿瘤，是最常见的非霍奇金淋巴瘤类型，约占全部非霍奇金淋巴瘤的25%～50%。DLBCL患者通常表现为进行性淋巴结肿大和/或淋巴结外病变，大多数患者就诊时已为III期或IV期，60%左右的早期患者可通过R-CHOP（利妥昔单抗、环磷酰胺、多柔比星、长春新碱和泼尼松）免疫化疗方案治愈。但仍有大约30-40%患者最终进展为复发或难治性DLBCL（R/R DLBCL）。已获批的R/R DLBCL新疗法近年来，全球监管机构批准了多款R/R DLBCL新疗法，详见下表。这些新疗法涉及抗体偶联药物（ADC）、CAR-T疗法、双抗、单抗和化药，作用靶点包括CD19、CD79b、CD20、CD3和XPO1。近年来全球获批的R/R DLBCL新药来源：药渡数据库（不完全统计）Yescarta、Polivy和Zynlonta属于ADC，但作用靶点不同。其中Yescarta于2017年10月被FDA批准用于治疗既往接受二线或多线系统治疗的R/R LBCL成人患者，包括DLBCL、原发纵膈大B细胞淋巴瘤（PMBCL）、高级别B细胞淋巴瘤（HGBL），以及源于滤泡性淋巴瘤（FL）的DLBCL。Polivy于2019年6月被FDA加速批准联合苯达莫司汀和Rituxan（利妥昔单抗）用于治疗既往已接受至少2种疗法的R/R DLBCL患者，2023年4月被FDA扩大批准用于联合R-CHP方案治疗未经治疗的DLBCL患者。Zynlonta于2021年4月被FDA加速批准单药用于治疗经过二线或以上全身系统性治疗的R/R DLBCL成人患者。Kymriah、Breyanzi和瑞基奥仑赛属于CAR-T疗法，均作用于CD19靶点。其中Kymriah于2018年5月被FDA批准用于治疗接受2种或多种系统疗法后的R/R LBCL成人患者。Breyanzi于2021年2月被FDA批准用于治疗至少接受过2种其他全身疗法后无应答或者复发的大B细胞淋巴瘤成人（LBCL）患者，2022年6月被FDA扩大批准作为二线疗法，用于治疗成人LBCL，包括未指定的DLBCL（包括由惰性淋巴瘤引起的DLBCL）、高级别B细胞淋巴瘤、原发性纵隔大B细胞淋巴瘤和3B级滤泡性淋巴瘤。瑞基奥仑赛于2021年9月被NMPA批准用于治疗经过二线或以上系统性治疗后成人患者的R/R LBCL，包括DLBCL非特指型、滤泡淋巴瘤转化的DLBCL、3b级滤泡淋巴瘤、原发纵膈大B细胞淋巴瘤、高级别B细胞淋巴瘤伴MYC和BCL-2和/或BCL-6重排（双打击/三打击淋巴瘤）。Epkinly和Columvi均属于CD3/CD20靶向双抗，其中Epkinly是FDA批准的首款治疗DLBCL的双特异性抗体疗法，2023年5月被FDA加速批准用于治疗R/R DLBCL，包括由惰性淋巴瘤发展而成的DLBCL以及高级别B细胞淋巴瘤（HGBL），这些患者已经接受过两种或多种系统治疗。Columvi于2023年3月获加拿大卫生部授权，有条件用于R/R DLBCL、起源于滤泡性淋巴瘤（trFL）的DLBCL或原发性纵隔B细胞淋巴瘤（PMBCL）成人患者的治疗，患者需已接受过二线或以上的全身治疗，不适合接受或不能接受CAR-T细胞治疗或既往接受过CAR-T细胞治疗。值得一提的是，Columvi是加拿大和全球首个获批的固定治疗时间、现货型CD20/CD3 T细胞衔接双特异性抗体。Minjuvi/Monjuvi是一种新型人源化Fc结构域优化的溶细胞性CD19靶向性免疫增强单克隆抗体，2020年7月被FDA加速批准，联合来那度胺用于治疗不符合自体干细胞移植（ASCT）条件的R/R DLBCL成人患者，包括源于低级别淋巴瘤的DLBCL。值得一提的是，Monjuvi是第一个获FDA批准用于一线治疗期间或治疗后病情进展的R/R DLBCL成人患者的二线疗法。Xpovio是一种全球首创、口服、选择性核输出蛋白抑制剂，通过结合并抑制核输出蛋白XPO1发挥作用，促使肿瘤抑制蛋白在细胞核内积累，从而重新启动和放大其肿瘤抑制的功能，导致癌细胞的凋亡，同时很大程度上让正常细胞免受损伤。2020年6月，该药被FDA批准用于治疗接受过至少2种系统疗法的R/R DLBCL成人患者，包括滤泡性淋巴瘤（FL）引起的DLCBL。在研R/R DLBCL药物此外，目前全球还有多款新药被开发用于治疗R/R DLBCL，如再生元的Odronextamab、强生的JNJ-67856633、嘉葆药银的JDB175、信达生物的IBI110、倍特药业的BT-1053、默沙东的MK-2140、百利药业的GNC-038。OdronextamabOdronextamab是一种铰链稳定、基于人IgG4的CD20×CD3双特异性抗体（Ab），可结合B细胞表面的CD20和T细胞表面的CD3，从而触发T细胞介导的恶性B细胞毒性。在ELM-1研究（Ph1，NCT02290951）中，Odronextamab在既往接受≥2线治疗（LOT）的DLBCL患者中表现出令人鼓舞的活性。接受剂量≥80mg Odronextamab治疗的DLBCL患者的ORR为53%，CR率为53%。12个月时持续缓解率为88%。JNJ-67856633JNJ-67856633是强生开发的一款MALT1抑制剂，MALT-1是一种参与T细胞和B细胞淋巴细胞活化的蛋白质。目前，强生正在开展多项JNJ-67856633单药或与其它药物联合治疗的临床研究，针对的适应症包括非霍奇金淋巴瘤、慢性淋巴细胞白血病等。JDB175JDB175是一个具有高选择性的第二代BTK口服抑制剂，BTK是B细胞受体通路中的关键蛋白分子，参与B细胞的增殖、运输、趋化和黏附，在不同类型血液系统恶性肿瘤中广泛表达，抑制其活性可产生明显的抗肿瘤效应。临床前试验表明：与同类药物相比，JDB175具有良好的BTK选择抑制性，且安全性与耐受性表现良好，在DLBCL中具有很好的抗癌活性。MK-2140MK-2140是一款ROR1靶向ADC，最早由VelosBio主导开发，2020年VelosBio被默沙东以27.5亿美元收购后，并入默沙东研发管线。评估MK-2140（2.5mg/kg）单药治疗R/R DLBCL患者有效性和安全性的开放标签、单臂2期临床试验WaveLINE-004的早期结果显示：经MK-2140治疗后，患者的ORR为30%（6/20），包括2例CR和4例PR。GNC-038GNC-038是百利药业基于GNC平台开发的四特异性结构的“靶向免疫”抗体，具有靶向CD19、CD3、PD-L1和4-1BB四个抗原的结构域，可激活T细胞的第一信号和第二信号，通过抗CD19、PD-L1结构域靶向并杀伤肿瘤细胞。随着新疗法的兴起，复发或难治性弥漫性大B细胞淋巴瘤（R/R DLBCL）的治疗迎来更多新选择。整体来看，目前已获批的新疗法作用靶点相对集中，主要是CD19、CD3/CD20，药物类型比较多样，涉及ADC、CAR-T疗法和双抗。此外，目前全球还有多款在研R/R DLBCL疗法，这些在研疗法作用靶点新颖，涉及MALT1、ROR1等，而且在研新疗法还涉及新的药物类型，如四特异性抗体。期待未来R/R DLBCL领域早日批准更多新药，给患者提供更多的治疗选择。END👇关注药渡数据媒体矩阵

This announcement contains inside information C4X Discovery Holdings plc("C4XD", "C4X Discovery" or the "Company") Half-year results for the six months ended 31 January 2023 Up to $402 million AstraZeneca deal for NRF2 Activator programme; Third global out-licensing deal executed Future strategic focus to deliver high value small molecules to treat immuno-inflammatory diseases Launched PatientSeek, a Precision Medicine platform for optimised patient selection based on its Taxonomy3® genetic analysis technology MANCHESTER, United Kingdom, April 26, 2023 (GLOBE NEWSWIRE) -- C4X Discovery Holdings plc (AIM: C4XD), a pioneering Drug Discovery company, today announces its half-year results for the six months ended 31 January 2023. Dr Clive Dix, CEO of C4X Discovery, said:"C4XD has continued to make significant strides across our portfolio during the period, culminating in our third global out-licensing deal, this time with AstraZeneca for our NRF2 Activator programme worth up to $402 million. This external validation of our ability to generate high-quality small molecule discovery programmes builds on previous deals with globally recognised partners Sanofi and Indivior and brings our total potential deal value to $1.2 billion1. "I'm excited that following a review of our expertise and previous successes, our strategy is now focused on treatments for immuno-inflammatory diseases. With our proven expertise in drug discovery and our rigorous approach to programme development, we believe that a more focused approach on immuno-inflammatory diseases will allow us to harness our skillset and take the development of our programmes further, providing greater value for shareholders." Operational Highlights (including post-period events) Indivior's Phase 1 multiple ascending dose clinical trial of C4XD's oral Orexin-1 receptor antagonist, C4X_3256 (INDV-2000), for substance use disorder is ongoing.Sanofi is progressing C4XD's IL-17A inhibitor programme for inflammatory diseases towards the next milestone.C4XD signed an exclusive worldwide licensing agreement with AstraZeneca in November 2022, worth up to $402 million, for its NRF2 Activator programme.α4β7 integrin inhibitor programme for inflammatory bowel disease delivered compounds showing improved activity at a lower dose compared to example competitor clinical compounds in a pharmacodynamic model after oral dosing.MALT-1 inhibitor programme for cancer examined a lead compound in a mouse xenograft study that showed equivalent efficacy at equivalent dose to the Johnson & Johnson clinical compound JnJ-67856633 (in Phase 1) and the project is moving forward to identification of candidate shortlist molecules.C4XD internal portfolio expanded in inflammatory diseases and new programmes identified to progress into Lead Optimisation and beyond.C4XD launched PatientSeek, a Precision Medicine platform for optimised patient selection based on its Taxonomy3® genetic analysis technology, following key results from a collaboration with Australia's Garvan Institute of Medical Research ("Garvan Institute").Dr Nick Ray has been appointed as Chief Scientific Officer. Financial Highlights Revenue was £1.7 million (January 2022: £0.1 million)Total loss after tax of £3.9 million or 1.55 pence per share (January 2022: £4.5m or 1.98 pence per share)R&D expenses was £5.2 million (January 2022: £3.9m), reflecting focused investment in key Drug Discovery programmesNet assets of £13.6 million (January 2022: £15.2m)Net cash as at 31 January 2023: £9.6 million (31 January 2022: £11.7m) Analyst webcast and conference call today Dr Clive Dix, Chief Executive Officer, and members of the management team will host a webcast for analysts at 9:30am BST today. The webcast can be accessed online at: https://www.lsegissuerservices.com/spark/C4xDiscoveryHolding/events/d062ff53-5db5-4b93-a428-089daeee0030 A copy of the final results presentation will be released later this morning on the Company website at www.c4xdiscovery.com. 1. Total deal value calculation based on exchange rates at the time of each deal. - Ends - Contacts C4X Discovery Holdings Mo Noonan, Communications+44 (0)787 6444977 Panmure Gordon (UK) Limited (NOMAD and Broker) Freddy Crossley, Emma Earl (Corporate Finance)+44 (0)20 7886 2500Rupert Dearden (Corporate Broking) C4X Discovery Media - Consilium Strategic Communications Mary-Jane Elliott, Chris Gardner, Matthew Neal+44 (0)203 709 5700 Notes to Editors: About C4X Discovery C4X Discovery ("C4XD") is a pioneering Drug Discovery company, combining scientific expertise with cutting-edge Drug Discovery technologies to efficiently deliver world-leading medicines. We have a highly valuable and differentiated approach to Drug Discovery through our enhanced candidate molecule design and patient stratification capabilities, generating small molecule drug candidates across multiple disease areas focused on immuno-inflammation. Our commercially attractive portfolio ranges from early-stage target opportunities to late-stage Drug Discovery programmes and we have three commercially partnered programmes with one candidate in clinical development. For more information visit us at www.c4xdiscovery.com or follow us on twitter @C4XDiscovery. Corporate Overview We have continued to make strong progress across the entire portfolio, both during the period and into the beginning of 2023. Our most significant news was announced in November with the out-licensing of our NRF2 Activator programme to AstraZeneca for up to $402 million, including $2 million upfront, and up to $16 million in potential pre-clinical milestone payments, plus the potential for tiered single-digit royalties. Our portfolio of partnered programmes continues to advance. Indivior's Phase I multiple-ascending dose clinical trial of C4XD's Orexin 1 Antagonist candidate C4X_3256/INDV-2000 is underway and, following the first milestone received from Sanofi, our IL-17A Inhibitor programme is advancing through pre-clinical studies towards the next milestone. We look forward to hearing how these programmes progress throughout the year. Following a review of our expertise and previous successes, C4XD is evolving its strategy to become a company focused on treatments for immuno-inflammatory diseases. With the majority of our portfolio already focused on immuno-inflammatory diseases, a proven drug discovery expertise and an expert team of scientists who understand this disease area, we believe that with this approach we can harness our skillset and take the development of our programmes further, providing greater value for shareholders. Our internal portfolio will now focus on the discovery and development of novel small molecule medicines with Best-in-Class and First-in-Class potential to treat patients across a range of immuno-inflammatory diseases. Our lead internal programme, focused on oral small molecule inhibitors of α4β7, has the potential to expand patient access to α4β7 inhibitor therapy for the treatment of inflammatory bowel disease ("IBD"). This programme is making significant headway through late-stage discovery and progressing towards pre-clinical studies. We have further immuno-inflammatory programmes in early discovery and we anticipate moving the two most promising of these into Lead Optimisation within the next 18 months. In line with our new focus on immuno-inflammatory diseases, the decision has been taken to streamline our portfolio and prioritise resources, and we therefore plan to out-license our pre-clinical MALT-1 inhibitor programme for oncology. In January 2023, we were delighted to appoint Nick Ray as our Chief Scientific Officer. Nick has been with C4XD for seven years, most recently as SVP Drug Discovery and also leading the medicinal chemistry, structural analysis and computational chemistry/cheminformatics teams. He has played a key role in the growth of C4XD and his in-depth scientific expertise has enabled C4XD to develop a growing portfolio of high-quality small molecule programmes. Nick's leadership will be invaluable as we look to take these programmes further into development. In February 2023, following a successful research collaboration with Garvan Institute, we announced the launch of C4XD's new platform for patient stratification, PatientSeek (powered by Taxonomy3®) - see study details in the Portfolio Review. The results of the study demonstrate PatientSeek's ability to optimise patient selection and its potential to match the most effective treatments with groups of patients who are most likely to benefit thereby ensuring the right drug is given to the right patient, based on their genetics. C4XD has already identified subgroups in a number of immuno-inflammatory diseases using PatientSeek and we will be exploring their application in bringing precision medicine approaches to these patient populations. The Company has a sufficient cash position and manageable fixed cost base. Cash, cash equivalents, short-term investments and deposits were £9.6 million at 31 January 2023 (31 January 2022: £11.7 million). R&D investment of £5.2 million in the six months ending 31 January 2023 (January 2022: £3.9 million), reflecting focused investment in key Drug Discovery programmes. Administrative Expenses remained steady at £1.6 million for the six months ended January 2023 (January 2022: £1.6 million). Portfolio Review Addictive disorders (Orexin-1 Antagonist) - out-licensed to Indivior Phase 1 multiple ascending dose study ongoing Under C4XD's milestone and royalties agreement with Indivior worth up to US$284 million for C4XD's oral Orexin-1 receptor antagonist C4X_3256 (INDV-2000) for the treatment of substance use disorders, Indivior has completed the Single Ascending Dose (SAD) Phase 1 study with no events of clinical concern. The Multiple ascending dose (MAD) study is progressing with Last Subject Last Visit (LSLV) scheduled for July 2023, and with other clinical, non-clinical and chemical/formulation development activities proceeding to plan. Opioid addiction is an increasing burden on the healthcare system, particularly in the US but is a growing global issue. According to the U.S. Center for Disease Control & Prevention (CDC), more than 107,937 people are predicted to have died from drug overdose, up 56% in the 12-month period ending August 2022, with 73,369 of these deaths attributed to synthetic opioids, up 115%1. Inflammation (IL-17A Inhibitor) - out-licensed to Sanofi Sanofi-led programme making significant progress Under the exclusive worldwide licensing agreement worth up to €414 million, Sanofi continues to make strong pre-clinical progress towards the second milestone; C4XD received the first milestone payment of €3 million in July 2022. The small molecules in C4XD's oral IL-17A inhibitor programme can selectively block IL-17 activity whilst maintaining molecular size of the molecule in the traditional "drug-like" range. A novel, potent oral series of IL-17A inhibitors that significantly reduce IL-17 induced inflammation in vivo is being optimised. Sanofi has development and commercial rights to the programme and is continuing to work with C4XD in the next discovery phase, utilising our Conformetrix technology, interpretation and application to compound design as the programme progresses towards the clinic. Inflammation (NRF2 Activator) - out-licensed to AstraZeneca Programme continues to move forward under AstraZeneca's ownership C4XD signed an exclusive worldwide licensing agreement with AstraZeneca in November 2022, worth up to $402 million, for its NRF2 Activator programme. AstraZeneca will develop and commercialise an oral therapy for the treatment of inflammatory and respiratory diseases with a lead focus on chronic obstructive pulmonary disease (COPD). Under the terms of the agreement, C4XD will receive pre-clinical milestone payments worth up to $16 million including $2 million upfront, ahead of the first clinical trial. In addition, C4XD will receive a further potential $385.8 million in clinical development and commercial milestones and tiered mid-single digit royalties upon commercialisation. Inflammation is a key driver in many pathological conditions. NRF2 plays a pivotal role in controlling the expression of antioxidant genes that ultimately exert anti-inflammatory functions. Targeting the NRF2 pathway to reduce inflammatory damage offers the potential for a new approach to treat a variety of inflammatory diseases. Interest in this therapeutic approach covers multiple therapeutic areas including chronic obstructive pulmonary disease, atopic dermatitis, IBD, pulmonary arterial hypertension and sickle cell disease. Inflammation (α4β7 Integrin Inhibitor) Programme transitioned into Lead Optimisation C4XD's oral α4β7 integrin inhibitor programme has identified multiple series of novel, potent and selective α4β7 integrin inhibitors for the treatment of IBD. Effective antibody therapy against this target is already approved, removing the clinical target risk, but an effective oral therapy remains highly sought after. During 2021, Morphic Therapeutic's Phase 1 clinical study demonstrated high target occupancy in blood at developable doses but with a twice daily profile. C4XD's programme is targeting a much desired once-a-day profile. Oral bioavailability has been demonstrated and there is particular focus on improving PK properties to achieve a good oral half-life. C4XD has compounds that match or exceed both whole blood potency and selectivity values when compared to examples from current clinical patent estates, with correspondingly improved activity at a lower dose when profiled in a T-cell gut-homing pharmacodynamic model. Haematological Cancer (MALT1 Inhibitor) Moving towards identification of pre-clinical candidate shortlist MALT1 is one of the key regulators of B-cell receptor (BCR) and T-cell receptor (TCR) signalling. Mutations that lead to constitutive activation of MALT1 are associated with aggressive forms of non-Hodgkin B-cell lymphoma and inhibition of MALT1 has potential therapeutic applicability as a mono therapy for MALT1-driven cancers such as activated B-cell diffuse large B-cell lymphoma (ABC-DLBCL) and in combination with BTK and Bcl inhibitors across multiple haematological indications, as well as broader potential in solid tumours and inflammation. Our Conformetrix technology has yielded multiple structurally distinct series, two of which have progressed into Lead Optimisation. Profiling of a Lead compound in a mouse xenograft study has shown equivalent efficacy at equivalent dose to the Johnson & Johnson clinical compound JnJ-67856633 (in Phase 1) and the programme is moving forward to identification of candidate shortlist molecules. C4XD has initiated partnering discussions for this programme. Expansion of Pipeline As we look to scale our portfolio, early-phase programmes targeting a number of targets across a range of immuno-inflammatory diseases are being resourced to identify those with the highest potential to warrant increased spend and prosecution to and through Lead Optimisation and eventually into the clinic. These programmes target clear unmet medical need, combined with significant commercial potential and a unique opportunity to produce valuable chemical equity through interpretation of conformational insight via C4XD's Conformetrix technology. Additionally, we are using our PatientSeek platform (vide infra) to inform our target selection choices, based on identification of patient stratification opportunities and improved trial design. Details of each programme will be provided once they have matured to Lead Optimisation stage. PatientSeek C4XD has launched a precision medicine platform, PatientSeek, based on its Taxonomy3® technology, following insights from a successful research collaboration with Garvan Institute of Medical Research. In the collaboration, C4XD provided Garvan Institute with the genetic signatures for its PatientSeek sub-groups in Parkinson's disease. Garvan researchers then applied this as part of a retrospective analysis of a failed Phase 3 Parkinson's clinical trial that had not reached its primary endpoint, to assess if a genetic subgroup of participants showed a benefit from the therapeutic. Very encouragingly, PatientSeek identified a subgroup that responded to the trial drug. These results provide the first validation of PatientSeek's ability to identify patient subgroups to optimise patient selection, which in turn could lead to enhanced probability of targeted success in clinical trials. The results from this study will be submitted for publication in a peer reviewed journal. Whilst this study was focused on Parkinson's disease, the PatientSeek platform is disease agnostic and can be applied to any complex genetic disease and we will look to expand and explore the immuno-inflammatory diseases subgroups for application in our own portfolio. Outlook C4XD has continued to make huge strides across our portfolio during the period, including our third global out-licensing deal, this time with AstraZeneca for our NRF2 Activator programme worth up to $402 million. This brings our deal value to a total of $1.2 billion with large pharmaceutical companies, further validating our reputation for generating high-quality small molecules. Following a review of our expertise and previous successes, C4XD is evolving its strategy to become a company focused on treatments for immuno-inflammatory diseases. With our proven expertise in drug discovery and our rigorous approach to programme development, we believe that a more focused approach on immuno-inflammatory diseases will allow us to harness our skillset and take the development of our programmes further, providing greater value for shareholders. 1. https://www.indivior.com/resources/dam/id/1147/Annual%20Report%20and%20Accounts%202022.pdf2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4530463/3. Plaque Psoriasis: Global Drug Forecast and Market Analysis to 2027, GlobalData, December 2018 Interim consolidated statement of comprehensive incomeFor the six months ended 31 January 2023 Six months Six months Year to to to 31 January 2023 31 January 2022 31 July2022 (Unaudited) (Unaudited) (Audited) £000 £000 £000 Notes Revenue31,676 66 2,699 Cost of sales (22)(59)(130) Gross profit 1,654 7 2,569 Research and development expenses (5,194)(3,942)(9,426)Administrative expenses (1,638)(1,595)(3,665) Operating loss (5,178)(5,530)(10,522) Finance income 15 - - Finance costs (12)(7)(12) Loss before taxation (5,175)(5,537)(10,534) Taxation41,296 1,020 2,374 Loss for the period and total comprehensive loss for the period (3,879)(4,517)(8,160) Loss per share: Basic loss for the period5(1.55)p(1.98)p(3.57)pDiluted loss for the period5(1.55)p(1.98)p(3.57)p Interim consolidated statement of changes in equityFor the six months ended 31 January 2023 Issued equityShareWarrantShare based paymentMergerCapital contributionRevenue capitalpremiumreservereservereservereservereserveTotal £000£000£000£000£000£000£000£000 At 01 August 20214,30253,043 979 1,191920195(41,344)19,286 Loss for the six months to31 January 2022-- - ---(4,517)(4,517)Issue of share capital-- - ---- - Expenses of options-- - ---- - Exercise of warrants11297 (11)---11 308 Share-based payments-- - 114--- 114 At 31 January 20224,31353,340 968 1,305920195(45,850)15,191 Loss for the six months to31 July 2022-- - ---(3,643)(3,643)Issue of share capital-- - ---- - Exercise of options315 - ---- 18 Exercise of warrants-- - ---- - Share-based payments-- - 238--- 238 At 31 July 20224,31653,355 968 1,543920195(49,493)11,804 Loss for the six months to31 January 2023-- - ---(3,879)(3,879)Issue of share capital2285,467 - ---- 5,695 Expenses of placing-(287)- ---- (287)Exercise of options15 - ---- 6 Exercise of warrants-- - ---- - Share-based payments-- - 214--- 214 At 31 January 20234,54558,540 968 1,757920195(53,372)13,553 Interim consolidated statement of financial positionAs at 31 January 2023 31 January 2023 31 January 2022 31 July 2022 (Unaudited) (Unaudited) (Audited) Notes£000 £000 £000 Assets Non-current assets Property, plant and equipment 43 30 47 Intangible assets 59 67 61 Goodwill 1,192 1,192 1,192 Right-of-use assets 563 266 707 1,857 1,555 2,007 Current assets Trade and other receivables 567 571 3,069 Income tax asset 3,661 3,073 4,427 Cash and cash equivalents 9,642 11,679 5,079 13,870 15,323 12,575 Total assets 15,727 16,878 14,582 Liabilities Current liabilities Trade and other payables (1,587)(1,390)(2,049)Lease liabilities (329)(171)(305) (1,916)(1,561)(2,354)Non-current liabilities Trade and other payables - - - Lease liabilities (258)(126)(424) (258)(126)(424) Total liabilities (2,174)(1,687)(2,778)Net assets 13,553 15,191 11,804 Capital and reserves Issued equity capital64,545 4,314 4,316 Share premium658,540 53,339 53,355 Share-based payment reserve 1,757 1,305 1,543 Warrant reserve 968 968 968 Merger reserve 920 920 920 Capital contribution reserve 195 195 195 Revenue reserve (53,372)(45,850)(49,493)Total equity 13,553 15,191 11,804 Approved by the Board and authorised for issue on 25 April 2023Brad HoyChief Financial Officer25 April 2023Interim consolidated cash flow statementFor the six months ended 31 January 2023 Six months Six months Year to to to 31 January 31 January 31 July 2023 2022 2022 (Unaudited) (Unaudited) (Audited) £000 £000 £000 Loss after tax and interest(3,879)(4,517)(8,160)Adjustments for: Depreciation of property, plant and equipment12 12 23 Depreciation of right-of-use assets143 111 212 Amortisation of intangible assets3 3 8 Share-based payments214 114 352 Finance income(15)- - Finance costs12 7 12 Taxation(1,296)(1,020)(2,374)Changes in working capital: Decrease/(increase) in trade and other receivables2,502 3 (2,496)(Decrease)/increase in trade and other payables(462)(321)338 Cash outflow from operating activities(2,766)(5,608)(12,085)Research and development tax credit received2,063 - - Net cash outflow from operating activities(703)(5,608)(12,085) Cash flows from investing activities: Purchases of property, plant and equipment(8)(10)(36)Finance income15 - - Net cash outflow from investing activities7 (10)(36) Cash flows from financing activities: Payment of lease liabilities(155)(114)(229)Proceeds from the issue of ordinary share capital5,701 308 326 Expenses of placing(287)- - Net cash inflow from financing activities5,259 194 97 Increase/(decrease) in cash and cash equivalents4,563 (5,424)(12,024)Cash and cash equivalents at the start of the period5,079 17,103 17,103 Cash, cash equivalents and deposits at the end of the period9,642 11,679 5,079 Notes to the interim financial reportFor the six months ended 31 January 2023 1. Corporate information The principal activity of the C4X Discovery Holdings plc is research and development, a review of which is included in the Chairman's and CEO's Statement. C4XD is incorporated and domiciled in the United Kingdom and its registered number is 09134041. The address of the registered office is Manchester One, 53 Portland Street, Manchester, M1 3LD. The interim financial information was approved for issue on 25 April 2023. 2. Accounting policies Basis of preparation The accounting policies adopted in this interim financial report are consistent with those followed in the preparation of the Group's annual report and accounts for the year to 31 July 2022. The interim financial information for the six months ended 31 January 2023 and 31 January 2022 is unaudited and does not constitute statutory accounts as defined in the Companies Act 2006. This interim financial report includes audited comparatives for the year to 31 July 2022. The 2022 annual report and accounts received an unqualified audit opinion and have been filed with the Registrar of Companies. These interim financial statements have been prepared in accordance with IAS34 Interim Financial Reporting. They do not include all the information required for a complete set of IFRS financial statements. However, selected explanatory notes are included to explain events and transactions that are significant to an understanding of the changes in the Group's financial position and performance since the last annual consolidated financial statements as at and for the year ended 31 July 2022. Basis of consolidation This interim financial report consolidates the financial statements of C4X Discovery Holdings plc and the entities it controls (its subsidiaries). 3. Revenue Six months toSix months toYear to 31 January31 January31 July 202320222022 £000£000£000Revenue recognised at a point in time - Right-to-use licence revenue - Milestone revenue1,652----2,555Revenue recognised over time - Research services revenue - Consultancy services24-66-144- Total Revenue1,676662,699 Revenue in the current period has been generated from contracts with two customers. In the current period a new contract was signed with a new customer which has been determined to have three performance obligations - the transfer of intellectual property which has been recognised as right-to-use licence revenue at a single point in time; the provision of consultancy and technical support which will be recognised over time in line with the level of consultancy provided; and the facility of on-going research which will be reimbursed on a pass-through cost basis. The revenue attributed to the delivery of research services was generated from one customer and is recognised over time. The progress is measured based on costs incurred to date as compared with the total projected costs for both the current and prior periods. Revenue In the prior periods was generated from a contract with a single customer. In the prior period, the milestone revenue was determined to have one performance obligation and was recognised at a point in time. The revenue attributed to the delivery of research services was recognised on the same basis as in the current period. 4. Taxation Six months to Six months to Year to 31 January 31 January 31 July 2023 2022 2022 £000 £000 £000 UK corporation tax losses in the period- - - Research and development income tax credit receivable(1,296)(1,020)(2,365)Adjustment in respect of prior periods- - (9) (1,296)(1,020)(2,374) 5. Loss per share 31 January31 January31 July202320222022 £000£000£000Loss for the financial period attributable to equity shareholders(3,879)(4,517)(8,160)Weighted average number of shares:No.No.No.Ordinary shares in issue250,048,502228,177,371228,675,845Number of exercisable share options and warrants305,19722,005,02112,231,972Ordinary shares in issue for purposes of diluted EPS250,353,700250,182,392240,907,817Basic and diluted loss per share (pence)(1.55)p(1.98)p(3.57)p The number of exercisable share options and warrants above are those deemed to be potentially dilutive in nature as their exercise price is less than the average share price for the period. As the group made a loss in the current and comparative period the effects of these potential ordinary shares are not dilutive. 6. Issued share capital and share premium Deferred sharesOrdinary shares Share capitalDeferred sharesWarrant reserveShare premium Total NumberNumber £000£000£000£000 £000 Ordinary and deferred shares as at 31 January 20222,025,000228,912,697 2,2892,02596853,339 58,621 Issue of share capital on exercise of options-319,275 3--15 18 Ordinary and deferred shares as at 31 July 20222,025,000229,231,972 2,2922,02596853,354 58,639 Issue of share capital on placing-22,781,200 228--5,467 5,695 Issue of share capital on exercise of options-106,425 1--5 6 Expenses of placing-- ---(287)(287)Ordinary and deferred shares as at 31 January 20232,025,000252,119,597 2,5212,02596858,539 64,053 7. Interim financial report A copy of this interim condensed financial report is available on C4XD's website at www.c4xdiscovery.com.