MPO

Conduit also appoints prominent intellectual property attorney Jeffrey Lindeman as a Consultant Leadership additions underscore Conduit’s commitment to strengthening and broadening its intellectual property portfolio through solid-form technology to maximize future value SAN DIEGO and LONDON, March 19, 2024 (GLOBE NEWSWIRE) -- Conduit Pharmaceuticals Inc. (Nasdaq: CDT) ("Conduit Pharmaceuticals" or "Conduit" or the “Company”) today announced the appointment of Dr. Joanne Holland as Chief Scientific Officer. Dr. Holland brings over 20 years of experience to the CSO role at Conduit, having amassed expertise across the entire development spectrum. This includes a deep knowledge base in identifying drugs that can be applied across multiple disease states, combining research and commercial skills to advance drugs to market, and working with premier scientific thought leaders. She has a specific focus in solid-form technology and its associated intellectual property, having held leadership positions at publicly traded companies in this space, as well as consulting roles for several pharmaceutical companies on all matters relating to solid-form technology. She has successfully shepherded multiple solid-form candidates from discovery stage into the clinic, and is the author of over 50 solid-form intellectual property patents. Dr. Holland earned a PhD in chemistry from the University of Leeds, UK, which was sponsored by Pfizer, Inc., before starting her career at companies including Millennium Pharmaceuticals and Stylacats Limited. In addition, Conduit has engaged Dr. Jeff Lindeman to consult on intellectual property strategies as part of the Company’s research and development of its solid-form candidates. An international speaker, Dr. Lindeman has authored book chapters on patent strategies relating to pharmaceutical solid-state forms. Prior to opening his consulting firm Two Notch Solutions, LLC, in 2009, Dr. Lindeman founded and then successfully sold J.A. Lindeman & Co. PLLC (now Raphael Bellum PLLC) and has over 30 years of intellectual property law experience, including as an adjunct patent law professor at American University and as a United States patent examiner. His role with the Company is as a consultant, not legal counsel. “The appointment of Jo as Chief Scientific Officer underscores Conduit’s commitment to optimizing the value of our current intellectual property assets, while concurrently fostering the creation of new intellectual property,” said Dr. David Tapolczay, Chief Executive Officer. “Jo and Jeff have over 20 years of experience working together, and their new leadership roles will significantly enhance our intellectual property state, strategically positioning Conduit for future out-licensing opportunities.” About Conduit Pharmaceuticals Conduit Pharmaceuticals (Nasdaq: CDT) have developed a unique business model to bring medicines to patients. Its novel approach addresses unmet medical need and lengthens the intellectual property for its existing assets through cutting-edge solid-form technology and then commercializes these products with life science companies. Conduit is led by a highly experienced team of pharmaceutical executives, including CEO, Dr. David Tapolczay, former Chief Executive Officer of UK-based medical research charity LifeArc; and the Chair of our Board, Dr. Freda Lewis-Hall, former Chief Medical Officer of Pfizer, Inc. Our Phase II ready pipeline, which consists of a HK4 Glucokinase Activator targeting auto-immune diseases and an MPO Inhibitor which we believe has the potential to treat Idiopathic Male Infertility, has undergone 20+ Phase I trials in over 1,000 patients. Forward-Looking Statements This press release contains certain forward-looking statements within the meaning of the federal securities laws. All statements other than statements of historical facts contained in this press release, including statements regarding Conduit's future results of operations and financial position, Conduit's business strategy, prospective product candidates, product approvals, research and development costs, timing and likelihood of success, plans and objectives of management for future operations, future results of current and anticipated studies and business endeavours with third parties, and future results of current and anticipated product candidates, are forward-looking statements. These forward-looking statements generally are identified by the words "believe," "project," "expect," "anticipate," "estimate," "intend," "strategy," "future," "opportunity," "plan," "may," "should," "will," "would," "will be," "will continue," "will likely result," and similar expressions. These forward-looking statements are subject to a number of risks, uncertainties and assumptions, including, but not limited to; the inability to maintain the listing of Conduit's securities on Nasdaq; the ability to recognize the anticipated benefits of the business combination completed in September 2023, which may be affected by, among other things, competition; the ability of the combined company to grow and manage growth economically and hire and retain key employees; the risks that Conduit's product candidates in development fail clinical trials or are not approved by the U.S. Food and Drug Administration or other applicable authorities on a timely basis or at all; changes in applicable laws or regulations; the possibility that Conduit may be adversely affected by other economic, business, and/or competitive factors; and other risks and uncertainties to be identified in the proxy statement/prospectus (as amended and supplemented) relating to the business combination completed in September 2023, including those under "Risk Factors" therein, and in other filings made by Conduit with the U.S. Securities and Exchange Commission. Moreover, Conduit operates in a very competitive and rapidly changing environment. Because forward-looking statements are inherently subject to risks and uncertainties, some of which cannot be predicted or quantified and some of which are beyond Conduit's control, you should not rely on these forward-looking statements as predictions of future events. Forward-looking statements speak only as of the date they are made. Readers are cautioned not to put undue reliance on forward-looking statements, and except as required by law, Conduit assumes no obligation and does not intend to update or revise these forward-looking statements, whether as a result of new information, future events, or otherwise. Conduit gives no assurance that it will achieve its expectations. Media: Sean Leous ICR Westwicke Sean.Leous@westwicke.com +1.646.866.4012 Investors: Bill Begien Conduit Pharmaceuticals Inc. bb@conduitpharma.com

PRESS RELEASE SUMMARY OF THE WEBCAST HELD ON MARCH 4, 2024 PROVIDING AN UPDATE ON AB SCIENCE DEVELOPMENT Paris, March 7, 2024, 3pm CET AB Science SA (Euronext - FR0010557264 - AB) is providing a summary of the live webcast held on March 4, 2024, giving an update on AB Science development. The webcast presentation is available on the company’s website, in the section « Press Releases »: https://www.ab-science.com/news-and-media/press-releases/ The presentation covered four topics: Status of conditional approval application of masitinib in ALS with EMA and Health CanadaStatus of the masitinib platform clinical development programStatus of masitinib licensing partnershipStatus of the microtubulin platform clinical development programStatus of masitinib and AB8939 intellectual property Status of conditional approval application of masitinib in ALS with EMA and Health Canada Regarding EMA, the application was filed in August 2022. An Oral Explanation was planned in January 2024, however, CHMP proposed that AB Science submit a written response to the List of Outstanding Issues at D195 of the procedure, instead of addressing these issues through the Oral Explanation, which is unusual. A decision is now expected by the end of Q2 2024.Regarding Health Canada, a Notice of Deficiency-Withdrawal (NOD/w) has been issued and AB Science intends to submit a Request for Reconsideration. This reconsideration process involves new assessors and offers the possibility to have an opinion from a panel of experts. A decision is now expected by the end of Q3/Q4 2024. Of note, the press release dated 26 February 2024 incorrectly stated that Health Canada issued a Notice of Non Compliance – Withdrawal (NON/w) when the decision issued was in fact a Notice of Deficiency – Withdrawal (NOD-W). The issuance of NOD-W or NON-W indicate different regulatory decisions. A NOD-W is issued if, during the scientific review of the response to a Notice of Deficiency (NOD), it is found that the submission/application remains deficient. On the other hand, a Notice of Non-Compliance Withdrawal is issued when, during the scientific review of the response to a Notice of Non-Compliance (NON), it is determined that the submission remains non-compliant. Three key major clinical objections and intended counterarguments for reconsiderations have been presented. They are the following: Amendments Multiple amendments have been made that create uncertainty on the reliability of study data. Several concerns were resolved, namely, changing study status from phase 2 to phase 3, the fact that multiple amendments may be an inevitability, that amendments were not data-driven, that the study had broad inclusion criteria and there may be a need to limit heterogeneity, and that post-onset decline of 1.1 point per month may be relevant.However, Health Canada was concerned that amendments were late and not sufficiently justified. AB Science intends to justify that the distinction between Normal and Fast progressors was made when the data were entirely blinded and in a sufficiently prospective manner since 88% of the data still needed to be acquired at that time, and that the amendment was justified to minimize expected high missing data due to discontinuations from Fast progressors (confirmed to be >50% at week 48). Missing data The concern regarding non-linearity of the ALSFRS-R data set distribution used for primary analysis (ANCOVA test) was resolved.However, Health Canada was concerned that the treatment of missing data using LOCF methodology could potentially create a bias in favor of treatment. AB Science intends to justify that sensitivity analysis of the primary analysis based on non LOCF recognized methods are successful and convergent (multiple imputational model, jump to reference, copy incremental model), and that the CAFS endpoint, incorrectly assumed by the Agency to be based on LOCF methodology, whereas it is not, approached the conventionally statistically significant outcome of 5% (p=0.0776), even though the study was not powered for this secondary endpoint. Application of EMA guideline on subgroups Health Canada was concerned that the new proposed claim in patients with ALS prior to any complete loss of function is considered post hoc and that overall survival benefit in this claim could have been biased by confounding factors. AB Science intends to justify that in the EMA guidance (EMA/CHMP/539146/2013) on the investigation of subgroups in confirmatory clinical trials, it is written that the guideline is applicable to a subgroup that has not been pre-specified.In this claim, the treatment effect is exceptionally strong based on CAFS (p=0.029) and survival (+22 months p=0.0192). Furthermore, OS is the gold standard endpoint in ALS and is unbiased regardless of post study treatments because no drug has demonstrated OS benefit (except riluzole, which was available to all patients) and because all patients had the same possibility to benefit from tracheostomy or permanent or non-permanent ventilation. Based on the supporting arguments and counterarguments outlined above, AB Science intends to submit a Request for Reconsideration. Other points of concern identified by the agency will also be responded to. Status of the masitinib platform clinical development program Masitinib offers a late stage and diversified platform of 8 indications, primarily centered around neuro-degenerative diseases (namely, amyotrophic lateral sclerosis, progressive form of multiple sclerosis, mild and moderate Alzheimer’s disease) and mast cell diseases (indolent systemic mastocytosis, mast cell activation syndrome), but also sickle cell disease, metastatic castrate refractory prostate cancer eligible to docetaxel, and COVID-19. In amyotrophic lateral sclerosis (ALS), no drug has generated a consensus based on definitive evidence of efficacy. Enrolment in the phase 3 confirmatory masitinib study (AB19001), is slower than that of the previous (AB10015) study, due to design features of the phase 3 (run-in period of 3 months, patient eligibility restricted to moderate ALS severity, exclusion of newly registered drugs and a blinded extension period).In multiple sclerosis (MS), there is no approved drugs for non-active secondary progressive MS and only one for primary progressive MS. Masitinib stands-out as the only non BTK inhibitor in phase 3 clinical development. The confirmatory phase 3 masitinib study (AB20009) is authorized by the FDA and key European countries and initiation is expected in 2024.In Alzheimer’s disease (AD), masitinib is positioned in mild and moderate forms of Alzheimer’s disease, where no novel treatment has been approved. New treatments have been approved in early Alzheimer. The confirmatory phase 3 masitinib study (AB21004) is authorized by FDA and key European countries with initiation expected in 2024.In indolent systemic mastocytosis (ISM), masitinib has a different positioning from other KIT-816 inhibitors and its benefits are optimal on different symptoms such as neurological symptoms, depression but also pruritus and flush. The confirmatory phase 3 masitinib study (AB15003) is on-going and additionally, a phase 2 study (AB20006) is also ongoing in MCAS, another mast cell disease not involving the KIT-816 mutation.In sickle cell disease (SCD), there is an increasing interest with several new drugs being in clinical development; however, unlike masitinib, none target mast cells, which are involved in Vaso Occlusive Crisis. A phase 1/2 study, financed by the RHU program for a budget of 10M€, is planned, with an objective to identify biomarkers of a mast cell signature and to assess the efficacy of masitinib in the treatment of acute and chronic complications. AB Science will be free to continue the development of masitinib in SCD based on phase 2 data with biomarkers.In metastatic castrate refractory prostate cancer (mCRPC) eligible to docetaxel, there is no drug registered in combination with docetaxel and there is an unmet medical need after failure to hormonotherapy and eligible to docetaxel. A first phase 3 study of masitinib in combination with docetaxel was positive. Submission of a confirmatory phase 3 study is planned in 2024, following scientific advice received from EMA and FDA, who both recommended to demonstrate benefit on radiographic progression free survival with no need to prove efficacy on overall survival.In COVID-19, read-out of two phase 2 studies is expected in 2024, the first evaluating masitinib anti-inflammatory activity in hospitalized patients in need of oxygen with moderate and severe COVID-19, and the second one evaluating masitinib anti-viral activity in ambulatory or hospitalized patients with symptomatic mild and moderate COVID-19 and with comorbidities. Status of masitinib licensing partnership Discussions for masitinib licensing with a pharmaceutical company are ongoing and the process is expected to be completed by the end of 2024. The scope of the license is mainly neurodegenerative indications, including ALS. The discussions are with companies that do not condition the signature of a binding offer to a positive opinion from EMA and Health Canada in ALS. AB Science is currently aiming to develop a liquid formulation for masitinib in ALS. A liquid formulation would be beneficial for ALS patients because they have difficulties in swallowing. A liquid formulation is beneficial for the masitinib development plan as differential pricing will be facilitated between ALS (liquid formulation) and other indications (tablets). The development of any new formulation will require bioequivalence studies and is expected to take two years. Status of the microtubulin platform clinical development program The microtubule destabilizer agents (MDAs) platform is focused in haemato-oncology with two drugs, AB8939 and AB12319. AB8939 has the potential to improve acute myeloid leukemia (AML) treatment based on three differentiating features of its mechanism of action. AB8939 is not metabolized by an enzyme called myeloperoxidase, produced by the disease itself, unlike other MDAs.AB8939 avoids multidrug resistance because it does not bind and is not transported by PgP/BRCP, so it is not washed out from the cells, unlike other MDAs.AB8939 has a strong synergistic effect with reference treatment azacitidine, called Vidaza. The phase 1 study of AB8939 has completed its first step (determination of maximum tolerated dose following 3 consecutive days of AB8939 treatment), and key agencies have authorized this study to proceed with the next step (determination of maximum tolerated dose following 14 consecutive days of AB8939 treatment). The phase 1 is expected to be completed in 2024 and a phase 2 will be initiated in 2025 with an intention to design the study to support accelerated approval. Status of masitinib and AB8939 intellectual property Masitinib intellectual property rights are protected until 2036 in mastocytosis, until 2037 in ALS, and potentially until 2041 in MS and ALZ and 2042 in prostate cancer. AB8939 intellectual property rights in AML are secured until 2036 through a ‘composition of matter’ patent and potentially until 2044 in AML with chromosome abnormality (MECOM) through a ‘second medical use’ patent. About AB ScienceFounded in 2001, AB Science is a pharmaceutical company specializing in the research, development and commercialization of protein kinase inhibitors (PKIs), a class of targeted proteins whose action are key in signaling pathways within cells. Our programs target only diseases with high unmet medical needs, often lethal with short term survival or rare or refractory to previous line of treatment. AB Science has developed a proprietary portfolio of molecules and the Company’s lead compound, masitinib, has already been registered for veterinary medicine and is developed in human medicine in oncology, neurological diseases, inflammatory diseases and viral diseases. The company is headquartered in Paris, France, and listed on Euronext Paris (ticker: AB).Further information is available on AB Science’s website: www.ab-science.com. Forward-looking Statements - AB ScienceThis press release contains forward-looking statements. These statements are not historical facts. These statements include projections and estimates as well as the assumptions on which they are based, statements based on projects, objectives, intentions and expectations regarding financial results, events, operations, future services, product development and their potential or future performance. These forward-looking statements can often be identified by the words "expect", "anticipate", "believe", "intend", "estimate" or "plan" as well as other similar terms. While AB Science believes these forward-looking statements are reasonable, investors are cautioned that these forward-looking statements are subject to numerous risks and uncertainties that are difficult to predict and generally beyond the control of AB Science and which may imply that results and actual events significantly differ from those expressed, induced or anticipated in the forward-looking information and statements. These risks and uncertainties include the uncertainties related to product development of the Company which may not be successful or to the marketing authorizations granted by competent authorities or, more generally, any factors that may affect marketing capacity of the products developed by AB Science, as well as those developed or identified in the public documents published by AB Science. AB Science disclaims any obligation or undertaking to update the forward-looking information and statements, subject to the applicable regulations, in particular articles 223-1 et seq. of the AMF General Regulations. For additional information, please contact: AB ScienceFinancial Communication & Media Relations investors@ab-science.com Attachment Summary Webcast March 4 2024 VEng VF

本文为转化医学网原创，转载请注明出处 作者：Sophia 导读： 开发模拟中性粒细胞杀伤机制的策略，涉及超氧化物歧化酶 （SOD） 和髓过氧化物酶 （MPO） 的酶级联反应，显示出作为癌症治疗的可行方法的潜力。然而，利用天然酶作为治疗方法受到各种挑战的阻碍。虽然纳米酶已经出现在癌症治疗中，但在一种纳米酶中开发SOD-MPO级联仍然是一个挑战。 2024年2月22日，中国科学院生物物理研究所阎锡蕴院士、范克龙研究员共同通讯在期刊《Nature Communications》上发表文章“Ultrasmall metal alloy nanozymes mimicking neutrophil enzymatic cascades for tumor catalytic therapy”， 研究发现模拟中性粒细胞酶级联的超小型金属合金纳米酶用于肿瘤催化治疗的机制。 https://www.nature.com/articles/s41467-024-45668-3 研究背景 01 纳米酶为酶催化疗法的开发提供了材料。纳米酶的纳米结构不仅赋予它们高效的催化功能，而且比天然酶具有更高的稳定性和更容易扩展的性。这使得纳米酶能够取代甚至超越天然酶，使其广泛应用于多个领域。纳米酶在调节肿瘤催化治疗和抗菌应用的ROS方面显示出巨大的潜力。然而，值得注意的是，由于这些纳米酶对 H2O2 的亲和力低，并且肿瘤微环境和微生物内部的 H2O2 水平通常较低，因此这些纳米酶的治疗效果可能会受到限制。在之前的报道中，开发了一种单原子纳米酶，能够催化从 H2O2 和 Cl− 中产生 O2·− 和 HClO。这有效地促进了耐药菌的消除和细菌感染的愈合。然而，由于缺乏类似SOD的活性，纳米酶无法催化H2O2作为MPO底物的生成，因此在处理过程中需要额外的H2O2。在治疗肿瘤时，肿瘤微环境中H2O2的限制水平（小于0.1 mM）使得还需要额外的H2O2，不仅增加了治疗的复杂性，而且增加了后续临床转化的难度。因此， 开发具有SOD和MPO双重酶样活性的纳米酶来模拟用于肿瘤治疗的中性粒细胞酶级联反应非常有价值，尽管具有挑战性。 研究结果 02 本文通过调整合金配比，开发了一系列超小型金属纳米酶：Au、Au3Pd1、Au2Pd2、Au1Pd3、Pd，发现这些纳米酶表现出合金比例依赖的SOD和MPO样活性，其中Au1Pd3合金纳米酶的级联活性最高。此外，我们利用理论计算阐明了这些纳米酶的催化机理，发现O2·−的高d波段中心和吸附能有助于SOD-MPO级联活性。重要的是， Au1Pd3合金纳米酶成功地模拟了中性粒细胞的SOD-MPO级联酶杀伤功能，并通过产生HClO和1O2引起DNA损伤和细胞凋亡，从而显示出优异的肿瘤治疗效果（图1）。 此外，Au1Pd3合金纳米酶还表现出良好的体内安全性，因为它们具有肿瘤特异性细胞毒性和小于6nm的超小尺寸，有助于其通过肾脏清除并防止在体内长期积累。我们共同成功开发了具有SOD和MPO样活性的超小型AuPd合金纳米酶，以模拟中性粒细胞酶级联反应，以实现高效和安全的肿瘤催化治疗。 模拟中性粒细胞酶级联的超小型金属合金纳米酶，用于肿瘤催化治疗。 研究结论 03 本研究，我们通过合金化Au和Pd开发了具有SOD和MPO类活性的纳米酶，当Au和Pd的比例为1：3时，纳米酶表现出最高的级联活性，这归因于超氧阴离子的高d波段中心和吸附能，这是通过理论计算确定的。 Au1Pd3合金纳米酶在雌性荷瘤小鼠中表现出优异的肿瘤治疗性能和安全性，其安全性归因于其超小尺寸引起的肿瘤特异性杀伤能力和肾脏清除能力。这项工作共同开发了超小的AuPd合金纳米酶，该纳米酶模拟中性粒细胞酶级联，用于催化治疗肿瘤。 参考资料： https://www.nature.com/articles/s41467-024-45668-3 注：本文旨在介绍医学研究进展，不能作为治疗方案参考。如需获得健康指导，请至正规医院就诊。 热门·直播/活动 🕓 上海｜3月01日-02日 ▶第三届长三角单细胞组学技术应用论坛暨空间组学前沿论坛将在上海召开，诚邀您的参与！ 点击对应文字 查看详情