PHAXIAM Therapeutics SA

A Phase 2 study sponsored by Assistance Publique – Hôpitaux de Paris (AP-HP) as part of the hospital-based clinical research program (PHRC) Evaluation of the efficacy of a local treatment with PHAXIAM’s anti- S. aureus phages added to the standard treatment by surgery and antibiotics 80 patients to be enrolled in 27 French clinical centers Validation of the study protocol by the ANSM expected in H1 2025 Lyon (France), October 9, 2024 – 06:00pm CEST - PHAXIAM Therapeutics (Euronext: PHXM - FR0011471135), a biopharmaceutical company developing innovative treatments for severe and resistant bacterial infections, today announces the validation, as part of the French Hospital Clinical Research Program (PHRC), of a new Instigator-sponsored trial (IST), PHAGOSCARPA, in extra-cavitary vascular grafts implant infections caused by Staphylococcus aureus (S. aureus) . The number of vascular prostheses is increasing every year and vascular graft infection occurs in 1-5% of patients. Staphylococcus aureus is the most common bacterium involved (20-53%) in extra-cavitary (EC) vascular graft infection (VGI). The mortality rate is very high and estimated at 10-25% within 30 days after diagnosis and over 50% after 1 year. The risk of amputation ranges from 4 to 14%. These infections are difficult to eradicate due to biofilm formation and increasing antimicrobial resistance. The standard of care (SoC) includes surgical detersion of the surgical site and vascular graft with prolonged antibiotic treatment. VGI are difficult and costly to treat, despite advances in antibiotic management and new operative techniques. Satisfactory results have been obtained for the compassionate clinical use of PHAXIAM’s phage therapy for vascular graft infection when conventional treatment has failed. Lytic phages, unaffected by resistance to anti- S. aureus antibiotics, can be used in combination with antibiotics and have a rapid bactericidal and synergistic action against biofilm. Phage tolerance was good, with no signs of local or systemic toxicity, in clinical case series. Based on these promising results, PHAGOSCARPA was designed as a multicentric, randomized and blinded phase 2 study to evaluate the efficacy of PHAXIAM’s anti- S. aureus phages administered locally vs. SoC. The primary endpoint consists in the therapeutic success rate at 3 months, including: absence of clinical signs of infection (T°C≤38.0°C; no local inflammation), normal graft function (no infection-related bleeding, ischemia distal, major amputation), absence of radiological evidence of infection on CT, with no other explanatory causes identified. Sponsored by Assistance Publique – Hôpitaux de Paris (AP-HP), the study received the approval from the Hospital Clinical Research Program and the Scientific Council of the National Network for Clinical Research in Infectious Diseases. The study plans to enrol 80 patients, recruited across 27 French clinical centers. The inclusion period is estimated at 24 months, with a patient follow-up for a further 12 months, i.e. an overall study duration of 36 months. The launch of the study is subject to validation of its clinical protocol by the French health authority (ANSM), expected in the first half of 2025. PHAXIAM is committed to ensuring the supply of the clinical doses required for the conduct of the study and will negotiate with the sponsor for access to the clinical data generated by this phase 2 trial. Sylvain Diamantis, MD, Head of the Infectious and Tropical Diseases Department at Melun Hospital and Principal Investigator of the study, stated: “We are very pleased with the work carried out in preparation for this study involving 27 French clinical centers and targeting a severe resistant infection. The number of vascular graft implants increases every year and Staphylococcus aureus is the most common bacterium involved in case of graft infection. We think that the use of phage therapy in combination with standard treatment could contribute to improve the treatment of patients who often face a therapeutic impasse, and we are thrilled to start this new trial.” Pascal Birman, MD, Chief Medical Officer of PHAXIAM , concluded: “This validation of a new investigational-sponsored trial, based on the data from compassionate treatments, once again reflects the added value that phage therapy could bring to the treatment of severe and resistant bacterial infections. We are proud to support the AP-HP in this study by providing clinical batches of our anti-S. aureus phages which have already shown promising results in compassionate use. We look forward to starting as soon as possible the enrolment in this new indication with high unmet medical needs.” As a reminder, two other investigator-sponsored trials, in which PHAXIAM is involved, are also planned in high-value indications: Phase 2 study (60 patients) in Diabetic Foot Ulcer (DFU) sponsored by Nîmes Hospital (France), targeting DFU infections due to mono-bacterial S. aureus infection and ready for First Patient-In, expected before the end of 2024. Phase 2 study (180 patients) targeting nosocomial pulmonary infections due to P. aeruginosa , sponsored by La Pitié Salpêtrière Hospital in Paris (France), including patients with ventilator-associated pneumopathies (VAP). The filing of this study is planned in France (ANSM) in Q1 2025. About PHAXIAM Therapeutics PHAXIAM is a biopharmaceutical company developing innovative treatments for resistant bacterial infections, which are responsible for many serious infections. The company is building on an innovative approach based on the use of phages, natural bacterial-killing viruses. PHAXIAM is developing a portfolio of phages targeting 3 of the most resistant and dangerous bacteria, which together account for more than two-thirds of resistant hospital-acquired infections: Staphylococcus aureus , Escherichia coli and Pseudomonas aeruginosa . PHAXIAM is listed on the Euronext regulated market in Paris (ISIN code: FR0011471135, ticker: PHXM). PHAXIAM is part of the CAC Healthcare, CAC Pharma & Bio, CAC Mid & Small, CAC All Tradable, EnterNext PEA-PME 150 and Next Biotech indexes. For more information, please visit Contacts PHAXIAM Thibaut du Fayet CEO +33 4 78 74 44 38 investors@phaxiam.com NewCap Mathilde Bohin / Dušan Orešanský Investor Relations Arthur Rouillé Media Relations +33 1 44 71 94 94 phaxiam@newcap.eu Forward-looking information This press release contains forward-looking statements, forecasts and estimates with respect to the clinical programs, development plans, business and regulatory strategy and anticipated future performance of PHAXIAM and of the market in which it operates. Certain of these statements, forecasts and estimates can be recognized by the use of words such as, without limitation, “believes”, “anticipates”, “expects”, “intends”, “plans”, “seeks”, “estimates”, “may”, “will” and “continue” and similar expressions. All statements contained in this press release other than statements of historical facts are forward-looking statements. Such statements, forecasts and estimates are based on various assumptions and assessments of known and unknown risks, uncertainties and other factors, which were deemed reasonable when made but may or may not prove to be correct. Actual events are difficult to predict and may depend upon factors that are beyond PHAXIAM’s control. Therefore, actual results may turn out to be materially different from the anticipated future results, performance or achievements expressed or implied by such statements, forecasts and estimates. Investor should carefully read the risk factors section of the Company which can be found in the Company’s regulatory filings with the French Autorité des Marchés Financiers (AMF), including in the Company’s 2023 Universal Registration Document (Document d’Enregistrement Universel) filed with the AMF on April 5, 2024 and future filings and reports by the Company. Given these uncertainties, no representations are made as to the accuracy or fairness of such forward-looking statements, forecasts and estimates. Furthermore, forward-looking statements, forecasts and estimates only speak as of the date of this press release. PHAXIAM disclaims any obligation to update any such forward-looking statement, forecast or estimates to reflect any change in PHAXIAM’s expectations with regard thereto, or any change in events, conditions or circumstances on which any such statement, forecast or estimate is based, except to the extent required by law. Attachment PR_PHAXIAM_Phagoscarpa_09-04-2024_EN

Continuous commitment to create a global leader in phage therapies to treat severe and resistant bacterial infections Ambitious development strategy on track with clear objectives set for the Prosthetic Joint Infections (PJI) strategic program Clinical readout expected before end of year 2024, including Updated Compassionate real life clinical data and PhagoDAIR pilot studyImminent Filing of Investigational New Drug Application (IND) in US and Clinical Trial Application (CTA) in Europe for GLORIA, the first global GLORIA Phase II study for the treatment of Staphylococcus aureus infections of PJI, with the aim of approval by the US and European regulatory agencies expected in Q4 2024Launch of the 1st global GLORIA Phase II study in Prosthetic Joint Infections (PJI) expected in Q1 2025 Cash and cash equivalents of €1.5 million as of June 30, 2024, not including the €6.8 million net proceeds from the capital increase, which was settled in early July 2024 Lyon (France), September 25, 2024 at 5:45 pm CEST – PHAXIAM Therapeutics (Euronext: PHXM), a biopharmaceutical company developing innovative treatments for severe and resistant bacterial infections, today provides a business and financial update for the first half of 2024. “Since the beginning of 2024, all PHAXIAM teams have been very committed and focused on the submission of the GLORIA Phase II study protocol to the American and European authorities and on the preparation of the launch of this study, expected in the first quarter of 2025. With the IND (U.S.) and CTA (EU) about to be very shortly filed, the most important catalyst of our development strategy is in reach. In addition, clinical data from PhagoDAIR, our pilot study, are expected in late 2024, as planned.“ stated Thibaut du Fayet, Chief Executive Officer of PHAXIAM. BUSINESS HIGHLIGHTS Phage therapy strategy focused on high-value indications PHAXIAM has refocused its clinical development on programs targeting patients with severe resistant infections of high medical needs, associated with high mortality and budget impact. Significant progress has been achieved over the year 2024 to accelerate PHAXIAM’s strategy deployment on key therapeutic programs, particularly with its lead program targeting Prosthetic Joint Infections caused by Staphylococcus aureus (S. aureus). Clinical and regulatory strategy in S. aureus program on track With its lead S. aureus program, PHAXIAM pursues the ambition to propose a therapeutic solution to patients who failed traditional antimicrobial treatments in complex mono-bacterial S. aureus infections in several high-value indications. Prosthetic Joint Infections (PJI): toward the first global Phase II study, enabling a potential Early Access Pathway Leveraging on promising activity signals from real-life compassionate treatments, with more than 120 patients already treated (data to September 2024), PHAXIAM is preparing the initiation of the 1st global (EU/US) Phase II POC study (GLORIA) for PJI patients (Hip or Knee prosthesis) having an open-surgery debridement (DAIR) in combination with antibiotics. As planned, PHAXIAM aims to: deliver PhagoDAIR pilot study preliminary data at the end of 2024, and the study’s complementary data in 2025,accelerate the transitioning of PJI clinical development effort into the ambitious global Phase II proof-of-concept study (GLORIA) to be launched in Q1 2025. GLORIA is PHAXIAM’s most important asset, having the highest priority. This multicentric, randomized, comparative Phase II proof-of-concept study, is expected to enroll 100 patients in Europe and the US. PHAXIAM is about to file the Investigational New Drug Application (IND) and the Clinical Trial Application (CTA) to US and European regulatory agencies respectively. The formal approval of the study is expected in Q4 2024, in view of starting patient enrollment in Q1 2025. Upon a successful completion of GLORIA Phase II study anticipated in Q3 2026, PHAXIAM may be eligible to an Early Access Pathway, paving the way for a pre-commercialization in Europe as soon as H2 2027. Endocarditis Infections (EI): patients’ enrolment ongoing in five French sites This Phase I PK study enrolls patients with resistant S. aureus infections in the cardiac chambers and valves. First clinical results are now expected around mid-2025. If positive, these results could allow PHAXIAM to: accelerate a clinical development in this indication; and use the intravenous (IV) administration for other indications requiring this administration route. Clinical study in complex mono-bacterial Escherichia coli (E. coli) infections, validated and ready for enrolment The objective of this E. coli program, including a Phase I PK study validated by the French Health Authority (ANSM), is to propose a therapeutic solution to patients having failed traditional antimicrobial treatment in complex mono-bacterial E. coli infections in the urinary tract. Confirmed valuable real-life clinical benefit data from compassionate treatments with more patients coming from European countries To date, PHAXIAM has treated more than 120 patients under compassionate treatment status, most of them suffering from hip or knee PJI. The vast majority is located in France but more and more compassionate patients, stemming from other European countries, are treated in their country with PHAXIAM phages: Sweden, Switzerland, Latvia, Romania and United Kingdom. Data from the first 77 patients evaluated so far show promising results with infection control at 3 months (clinical endpoint) reaching approximately 80%, considered as a significant improvement over standard of care (SoC) in this hard-to-treat patient population with severe resistant infections, often undergoing 2nd or 3rd line SoC antibiotic treatment. Early 2025, PHAXIAM is planning to file for another AAC (Autorisation d’Accès Compassionnel – early access program), in order to bring a new compassionate treatment to PJI patients associated with Pseudomonas aeruginosa (P. aeruginosa) resistance, complementing the first obtained AAC, associated with S. aureus resistance. Complementary Investigator-sponsored trials (IST) In addition to PHAXIAM’s sponsored clinical studies, two other investigator-sponsored trials, in which PHAXIAM is highly involved, are the opportunity to deliver additional clinical POC data in other high-value indications: Phase II study (60 patients) in Diabetic Foot Ulcer (DFU): this clinical study, sponsored by Nîmes Hospital, targets DFU infections due to mono-bacterial S. aureus infection; this study is ready for First-Patient-In, expected before the end of this year.Phase II study (180 patients) in complex Respiratory Tract Infections (cUTI): this clinical study, sponsored by La Pitié Salpêtrière Hospital in Paris, targets nosocomial pulmonary infections due to P. aeruginosa, including patients with ventilator-associated pneumopathies (VAP), a growing concern in hospital environments. The filing of this study is planned in France (ANSM) in Q1 2025. H1 2024 FINANCIAL RESULTS Key financial figures for the first half of 2024 compared with the same period of the previous year aresummarized below. As a reminder, PHAXIAM’s consolidated financial statements in IFRS standards for H1 2023 include ex-Pherecydes financial results as of the date of the merger, i.e. June 23, 2023. Consequently, PHAXIAM’s P&L information for the first 6 months of 2023 are mostly related to ex-Erytech activities only, while PHAXIAM’s consolidated balance sheet as of June 30, 2023, includes the financial positions of both merged companies. The full Financial Statements of PHAXIAM Therapeutics as of June 30, 2024 has been filed with the AMF on Wednesday, September 25, 2024, and is available on the company’s website. In thousands of euros H1 2024(6 months)H1 2023(6 months)Revenues ——Other income 1,093278Operating income 1,093278Research and development (6,406)(3,431)General and administrative (5,345)(9,245)Operating expenses (11,751)(12,676)Operating income (loss) (10,658)(12,398)Financial income 175331Financial expenses (132)(342)Financial income (loss) 43(11)Income tax (20)203Net loss (10,635)(12,201) Operating expenses of €11.7 million in the first half of 2024 were 7% lower (i.e. a €0.9 million reduction) than in the same period of the previous year. This decrease was driven by the 42% reduction of G&A expenses, including €3.4 million of non-recurring merger cost and €0.5 million of additional savings following Nasdaq delisting.This cost-cutting program was accelerated in the third quarter of 2024 to be in place as part of the 2025 budget. PHAXIAM’s operational R&D expenses in the first half of 2024 increased by €1.4 million (+41%) mostly on S. aureus development program, not included in the previous year's comparison. In addition, an impairment charge of €1.5 million on the endocarditis IP (EnDoCom) has been recorded. Net loss for the first half of 2024 was €10.6 million, compared with a net loss of €12.2 million for the same period of 2023. As of June 30, 2024, PHAXIAM had cash and cash equivalents totaling €1.5 million, compared with €10.5 million as of December 31, 2023. The €9 million decrease in cash position during the first half of 2024 was the result of a €8.2 million net cash utilization in operating activities including ~ €1 million in severance costs, €0.5 million in investing activities and €0.5 million used in financing activities, mostly related to lease reimbursement. On July 1, 2024, with the settlement & delivery of the €7.8 million capital increase, PHAXIAM's cash position increased by a net €6.8 million, after payment of capital increase costs. The Company believes that its current cash position can fund its existing programs and expected operating expenses into March 2025. The Company is studying all options to extend its financial visibility: cost reduction program, obtaining non-dilutive financing at the national and European level, search for strategic and institutional investors, etc. MANAGEMENT TEAM EVOLUTION Eric Soyer, former CFO / COO, is leaving PHAXIAM to pursue other interests. Frédéric Mathat succeeds him and will lead the Company’s Finance department as CFO.After a first robust experience in accounting and consolidation of listed companies (8 years at Nexity, the real estate branch of Vivendi, then 7 years at Sequana), Frédéric had been financial director of the Canson group for 11 years. He joined the pharmaceutical industry in 2017 to lead Erytech's finance department alongside Eric Soyer, until the merger with Pherecydes, in which he was instrumental and committed all along the process that led to the creation of PHAXIAM. Thibaut du Fayet, Chief Executive Officer of PHAXIAM, commented: “I would like to warmly thank Eric Soyer for his dedication during these 8 years spent at Erytech where he performed several fundraisings on Nasdaq and Euronext public markets, then at PHAXIAM where he was very instrumental in the success of the merger, as his contribution has been essential in designing PHAXIAM’s strategy; I wish him all the best for the near future. I am also delighted to welcome Frédéric as Chief Finance Officer. His extensive expertise and proven track record in finance add great value to our team.” KEY NEWSFLOW AND MILESTONES EXPECTED OVER THE NEXT 12 MONTHS Phase II IST in Diabetic Foot Ulcer (DFU) First-Patient-In expected in Q4 2024PhagoDAIR pilot study clinical readout expected before end of year 2024GLORIA global Phase II IND and CTA validation expected in Q4 2024GLORIA global Phase II First-Patient-In expected in Q1 2025Endocarditis Phase I PK study first readout expected around mid-2025 FIRST HALF 2024 WEBINAR DETAILS PHAXIAM management will hold a webinar today, Wednesday, September 25, 2024, at 6:00 pm CEST on the business highlights and financial results for the first half of 2024. Thibaut du Fayet, (CEO) and Frédéric Mathat (CFO), will deliver a brief presentation in French, followed by a Q&A session. The webinar, held in French, is accessible via this registering link. The replay of the webinar will be available on the Company's website in the following days. About PHAXIAM Therapeutics PHAXIAM is a biopharmaceutical company developing innovative treatments for resistant bacterial infections, which are responsible for many serious infections. The company is building on an innovative approach based on the use of phages, natural bacterial-killing viruses. PHAXIAM is developing a portfolio of phages targeting 3 of the most resistant and dangerous bacteria, which together account for more than two-thirds of resistant hospital-acquired infections: Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa. PHAXIAM is listed on the Euronext regulated market in Paris (ISIN code: FR0011471135, ticker: PHXM). PHAXIAM is part of the CAC Healthcare, CAC Pharma & Bio, CAC Mid & Small, CAC All Tradable, EnterNext PEA-PME 150 and Next Biotech indexes. For more information, please visit www.phaxiam.com Contacts PHAXIAMThibaut du FayetCEO+33 4 78 74 44 38 investors@phaxiam.com NewCap Mathilde Bohin / Dušan OrešanskýInvestor Relations Arthur Rouillé Media Relations+33 1 44 71 94 94 phaxiam@newcap.eu Forward-looking information This press release contains forward-looking statements, forecasts and estimates with respect to the clinical programs, development plans, business and regulatory strategy and anticipated future performance of PHAXIAM and of the market in which it operates. Certain of these statements, forecasts and estimates can be recognized by the use of words such as, without limitation, “believes”, “anticipates”, “expects”, “intends”, “plans”, “seeks”, “estimates”, “may”, “will” and “continue” and similar expressions. All statements contained in this press release other than statements of historical facts are forward-looking statements. Such statements, forecasts and estimates are based on various assumptions and assessments of known and unknown risks, uncertainties and other factors, which were deemed reasonable when made but may or may not prove to be correct. Actual events are difficult to predict and may depend upon factors that are beyond PHAXIAM's control. Therefore, actual results may turn out to be materially different from the anticipated future results, performance or achievements expressed or implied by such statements, forecasts and estimates. Investor should carefully read the risk factors section of the Company which can be found in the Company’s regulatory filings with the French Autorité des Marchés Financiers (AMF), including in the Company’s 2023 Universal Registration Document (Document d’Enregistrement Universel) filed with the AMF on April 5, 2024 and future filings and reports by the Company. Given these uncertainties, no representations are made as to the accuracy or fairness of such forward-looking statements, forecasts and estimates. Furthermore, forward-looking statements, forecasts and estimates only speak as of the date of this press release. PHAXIAM disclaims any obligation to update any such forward-looking statement, forecast or estimates to reflect any change in PHAXIAM’s expectations with regard thereto, or any change in events, conditions or circumstances on which any such statement, forecast or estimate is based, except to the extent required by law. Attachment PR_PHAXIAM_Q2-2024_BusinessFinancial_Update_EN

导读 长久以来，医用红细胞主要来源于人体血液捐献。合成红细胞技术改变了这样一种局面，它是一种革命性的方法，能解决血液短缺的问题。 这项技术包括体外培养或扩增人类红细胞，作为药物的载体。人工合成的红细胞有几个优点，包括没有致癌的DNA和RNA，在体内的半衰期长，能够携带高浓度的药物。 这项技术在制药行业越来越受欢迎，那么这项技术有哪些优点、类别，以及主要做这项技术的公司有哪些，本文进行初步的剖析。 值得一提的是，这个领域的明星公司、红细胞药物先驱 Rubius 2023年年初宣布解散，20亿美元市值蒸发殆尽，可以说这令红细胞药物发展前途未卜，这一技术仍有待完善。 红细胞是人体中数量最多的细胞，其占全部细胞数量的84%左右。长久以来，来源于捐献的血液都是人类医用红细胞的最主要来源。而合成红细胞技术，顾名思义，就是利用新型技术，以在体外培养或者扩增的方式，得到人体红细胞。更重要的是，以合成红细胞为载体，可以建立一个药物开发、制造和体内递送的通用平台，具有发展潜力。 合成红细胞技术起源于美国军方的“一个都不能少”政策。战场创伤引起的大量失血是战地死亡的一大原因，及时输血能挽救这些战地死亡。血液保存期仅仅为六周，而血液从美国本土收集到运输至战地需要四周，这造成战地血液保存期仅为两周，为战地后勤带来巨大的压力。因此，美国国防高级研究计划局（简称DARPA）在2008年向全世界召集在战地生产红细胞的建议。 最终，美国新基制药（Celgene）获得了DARPA的合同，并在人类历史上第一次成功利用造血干细胞，在体外培养出了正常的人红细胞。虽然这条路在理论上可行、可以实现试验，但是由于培养体系较为昂贵，美国国防高级研究计划局认为与其以高昂价格提供输血原料，还不如按照传统献血采集红细胞更为划算。 合成红细胞作为药物开发、制造和递送的载体具有以下几个优点： 1、红细胞没有细胞核、线粒体和核糖体，也就没有任何DNA和长链RNA。 红细胞药物没有致癌性，具有所见即所得的特性； 2、红细胞在人体内存活120天。因此，在红细胞内和表面的蛋白药物也能在体内存活120天，这可以极大延长蛋白药物在体内的半衰期； 3、红细胞具有极好的延伸性，能达到极小的毛细血管； 4、红细胞具有很大的表面积和体积。 比如说，一个红细胞表面可以放360万个抗体，红细胞内可以放2.8亿血红蛋白分子，这种特性可以保障药物的浓度； 5、红细胞特殊的结构使单位体积内红细胞数量很高，人血液中，每微升含有500万个红细胞； 6、输血已经是一种标准的临床医疗操作，因此红细胞药物可以作为货架化的细胞药物。 在制药行业中流行的被称为红细胞药物可以分成三类： 第一类是合成红细胞技术，也就是综合红细胞本身的天然特性和药用蛋白来治疗疾病。 这种类型还可以分为以下两种：一种是先合成造血干细胞，再在体外分化成的合成红细胞来治疗疾病，代表公司有Rubius Therapeutics和Plasti cell。另一种是修改体内成熟的红细胞用来治疗疾病，代表公司为Anokion。而另外两类也同样被称为红细胞药物，但是基本原理就与合成红细胞完全不同了，基本与合成红细胞并无关联。在此，我们只做简要介绍。 第二类是利用红细胞包裹药用蛋白或者小分子药物，提高药用蛋白或者小分子药物的体内半衰期，代表公司是EryDel和Erytech。 这类红细胞药物利用的是传统红细胞破膜及载药功能，基本没有核心专利技术，但对于药用蛋白和小分子药物的体内半衰期提高不多，市场影响力不大。 第三类是利用红细胞以提供大规模细胞膜，和不同的纳米分子、脂质体或固体脂质纳米粒等结合，来递送不同药物分子，包括蛋白、核酸、小分子等，代表公司为Arytha Biosciences、Cello、Nano blood和RxMP。 在这类红细胞药物中，红细胞仅仅是一类生物膜提供者，核心技术专利还是在于纳米分子、脂质体或固体脂质纳米粒。这类药物的优缺点和现有的纳米分子、脂质体或固体脂质纳米粒类似。 Rubius Therapeutics Harvey Lodish教授、Hidde Ploegh教授和Flagship Venture的Noubar Afeyan博士合作以Venture labs模式在2014年初成立Rubius Therapeutics。然后，公司入驻波士顿Lab Central生物孵化器，并于2018年7月在纳斯达克上市。Rubius Therapeutics的合成红细胞药物管线开始有三个方向，肿瘤免疫治疗、自身免疫性疾病和代谢酶缺乏型罕见病。后来，治疗代谢酶缺乏型罕见病的合成红细胞的临床试验不理想，这个研究方向被暂时搁置。 合成红细胞治疗肿瘤是通过肿瘤免疫方式，这包括两种方法，系统性提高免疫细胞数量和抗原特异性免疫细胞扩增。系统性提高免疫细胞数量是在合成红细胞表面表达4-1BBL和IL-15TP（RTX-240），这样的合成红细胞能启动NK细胞的扩增和活化，CD4和CD8T细胞的扩增和活化，同时还能启动CD8记忆细胞的扩增和生存。因此RTX-240主要是作为免疫力提升的疗法，可以和其他靶向性的肿瘤疗法联用。 而抗原特异性免疫细胞扩增则类似一种体内抗原特异T细胞启动的方法。合成红细胞在表面上表达IL-12、4-1BBL和携带特定肿瘤抗原的MHC1（RTX-321）。RTX-321能和拮抗特定肿瘤抗原的T细胞结合，并刺激这类T细胞扩增和启动。这类合成红细胞能在体内启动抗原特定的T细胞，有潜力成为通用的CAR-T疗法的替代品，而且由于合成红细胞上可以冰冻，并大规模生产，这也解决了CAR-T疗法的产量、储存和运输的问题。 合成红细胞治疗自身免疫性疾病则是基于2012年Jeffray Hubbell教授的研究，他发现依附在红细胞上的蛋白抗原能诱导T细胞程式性死亡，Hubbell教授后来成立了Anokion公司。Rubius Therapeutics利用蛋白融合的方法把抗原蛋白表达在合成红细胞表面，同样发现这样的合成红细胞能诱导抗原特异性的T细胞程式性死亡。这就称为了一种潜在的治疗自身免疫性疾病的手段，目前出于开发阶段。 Plasticell Plasticell是一家欧洲公司，法国和英国的科学家在体外培养造血干细胞和前体细胞制造红细胞在2011年以前处于世界领先，法国也是第一个实现体外合成红细胞在人体内存活的临床试验的国家。但是他们并不拥有合成红细胞药物相关的专利，因此虽然Plasticell具有完善的体外红细胞制造系统，却没有办法利用这些红细胞治疗除贫血外的疾病。 注：本文节选自由香港商务印书馆出版的《生命科技投资启示录·捕捉下一只独角兽》，文章已获出版社及作者授权，略有修改。 识别微信二维码，添加生物制品圈小编，符合条件者即可加入 生物制品微信群！ 请注明：姓名+研究方向！ 版 权 声 明 本公众号所有转载文章系出于传递更多信息之目的，且明确注明来源和作者，不希望被转载的媒体或个人可与我们联系(cbplib@163.com)，我们将立即进行删除处理。所有文章仅代表作者观点，不代表本站立场。