Central Manchester University Hospitals NHS Foundation Trust

Invizius estimates that about 20% of dialysis patients may have "angry blood," where an overzealous inflammatory response can lead to serious complications. Invizius has completed a first-in-human study of its approach to taming the immune system’s overreaction to dialysis—with the goal of addressing the complications that can come with “angry blood.” While you would normally want a zealous white blood cell to attack any newcomers to the body, to protect it against infections and the like, heightened inflammation can take its toll during hemodialysis.  As the living blood makes its way through the machine, every surface is a surface that triggers the foreign-body response: From the cells' point of view, none of it should be there. Enter Invizius’ H-Guard priming solution, which is run through the machine before each procedure. It coats the insides with a layer of proteins that effectively camouflage the dialysis hardware from the immune system—stealing a trick from certain bacteria that are capable of evading white blood cells, without triggering the cascading inflammatory reactions known as the complement system. Late last month, the Scotland-based company—and former Fierce 15 winner—announced that its first eight patients had been successfully treated in a phase 1 study. Analyses before and after dialysis showed that the blood filtration process worked as expected. Its next step will be to perform a phase 2b trial of hospitalized patients with acute kidney injuries, looking to see if H-Guard can lower the amount of time spent in the ICU or reduce renal damage from the immune system’s reactions to dialysis. “This is an important milestone for H-Guard and Invizius, allowing us to progress into a larger efficacy study showing the clinical benefits of controlling complement activation in [continuous renal replacement therapy] and a number of extracorporeal systems,” CEO Magnus Nicolson said in a statement. The priming solution is also being studied preclinically for use during heart bypass procedures and in other life support systems. A previous biomarker analysis study by the company screened blood samples from over 350 participants that undergo routine hemodialysis and found that patients can be categorized by their immune reactions to the procedure.  While chronic, low-grade inflammation is common among dialysis patients, those with the strongest responses can carry higher risks of developing serious complications—such as blood clots, organ damage or a wide range of other conditions—and may benefit the most from the addition of a product like H-Guard.  Dubbed “angry blood,” Invizius estimates that about one-in-five dialysis patients may be susceptible to the overreactions, out of the more than 3 million people worldwide who undergo the procedure multiple times per week. According to Invizius, the results of the biomarker study won “best abstract” last month at the annual meeting of the European Renal Association in Stockholm, as presented by Duha Ilyas, a clinical research fellow at the Manchester Royal Infirmary, part of the Manchester University NHS Foundation Trust and the site of the first-in-human trial. “This is the largest kinetic analysis of complement activation in routine haemodialysis (HD) ever undertaken in [the U.K.],” said study leader Sandip Mitra, a professor of renal medicine at the Manchester NHS trust. “Our results indicate patient-specific complement activation associated with inflammatory response during routine haemodialysis. Reduction in complement activation in HD may yield significant clinical outcome benefits.” The company previously raised £5.3 million in a 2021 series A round, joined by Mercia, Downing Ventures, Old College Capital, Scottish Enterprise, Solvay Ventures and Calculus Capital.

– HORACE trial initiated to evaluate the safety, efficacy and tolerability of BGT-OTCD in paediatric patients diagnosed with OTCD – LONDON, UK I November 06, 2023 I Bloomsbury Genetic Therapies Limited, a clinical-stage biotechnology company developing potentially curative treatments for patients suffering from rare neurological and metabolic diseases based on clinically proven gene therapy technologies, announced today that the Company’s collaborator, University College London (UCL), has enrolled the first patient in the Phase 1/2 clinical trial HORACE (Halting Ornithine transcarbamylase deficiency with Recombinant AAV in ChildrEn, NCT05092685) evaluating BGT-OTCD, Bloomsbury’s investigational AAV-LK03 gene therapy, in paediatric patients diagnosed with OTCD. HORACE is an open-label, safety, efficacy and dose-finding trial and will enrol up to 12 patients aged between 0 and 16 years old diagnosed with OTCD. UCL is the sponsor of the trial with financial support provided by the Company. HORACE will be conducted at a single treatment site, Great Ormond Street Hospital (GOSH) in London, UK, with three further referring UK sites: Evelina London Children’s Hospital, Royal Manchester Children’s Hospital and Birmingham Children’s Hospital. “OTCD is a devastating disease, particularly in the paediatric population. Current medical management of children with OTCD and dietary protein restriction do not prevent recurrent metabolic crises and don’t fully address the sub-clinical chronic neuronal damage caused by elevated blood ammonia levels, and its impact on children’s neurological development. I am therefore very pleased to have initiated the HORACE trial and look forward to evaluating BGT-OTCD as a potentially curative solution for children with OTCD”, said Dr Anupam Chakrapani, Consultant in Metabolic Medicine, GOSH and the trial’s Principal Investigator . “The initiation of our first clinical trial just a year after Bloomsbury’s launch is a landmark moment for us. BGT-OTCD is a highly differentiated gene therapy candidate for OTCD, relying on the best-in-class capsid AAV-LK03, whose efficacy, durability and safety has already been illustrated in the clinic in haemophilia A clinical trials, and we believe it has curative potential for both paediatric and adult patients suffering from OTCD,” said Adrien Lemoine, Co-Founder & Chief Executive Officer of Bloomsbury . “We look forward to UCL sharing initial clinical data with the OTCD community in due course.” For more information on the Phase 1/2 HORACE trial of BGT-OTCD for the treatment of OTCD, please visit: https://clinicaltrials.gov/study/NCT05092685 About Bloomsbury Genetic Therapies Bloomsbury is a clinical-stage biotechnology company, developing potentially curative treatments for patients suffering from rare neurological and metabolic diseases based on clinically proven gene therapy technologies. The Company was spun out of University College London and launched in October 2022 with funding from UCL Technology Fund. Bloomsbury is building a pipeline of highly differentiated first- or best-in-class programs. For more information, please visit www.bloomsburygtx.com About Ornithine transcarbamylase deficiency Ornithine transcarbamylase deficiency (OTCD) is a rare, X-linked genetic disorder that is characterised by complete or partial lack of the OTC enzyme. OTC enzyme is a key component of the urea cycle and patients with OTCD accumulate nitrogen waste in the form of excess ammonia (hyperammonaemia) in the blood, causing hyperammonaemic decompensations with symptoms including vomiting, impaired voluntary movement and progressive lethargy. If left untreated, these may progress to coma and life-threatening complications. While later onset disease can occur in adults with a milder form of the disorder, symptoms present within a few days of birth of males with severe OTCD. Patients are rapidly diagnosed (urine and blood biochemical analyses, gene sequencing) when they present at hospital/are admitted to intensive care with acute hepatic decompensation and hyperammonaemia. Current standard of care involves protein-restricted diets and ammonia-scavenger medications; however, these approaches can have a significant impact on patients’ quality of life and patients still face a lifelong risk of decompensation and neurological damage resulting in intellectual disability, developmental delays, and movement disorder. Liver transplant is the only curative option, but is often unavailable and comes with significant morbidity/mortality risk and lifelong immunosuppression and arginine supplementation. Over 10,000 patients suffering from OTCD have been identified worldwide. About BGT-OTCD BGT-OTCD is an investigational AAV-LK03 gene therapy designed to provide a potentially curative solution to OTCD patients following a one-time intravenous injection. AAV-LK03 was selected for its high tropism for liver cells and its success in other liver disorders such as haemophilia A. BGT-OTCD has been granted Orphan Drug Designation (ODD) for the treatment of OTCD by the European Commission (EC) and the US Food and Drug Administration (FDA) as well as Rare Pediatric Disease Designation (RPDD) from the FDA.  BGT-OTCD is currently being evaluated in HORACE (Halting Ornithine transcarbamylase deficiency with Recombinant AAV in ChildrEn; NCT 05092685), a Phase 1/2 clinical trial initiated in November 2023. SOURCE: Bloomsbury Genetic Therapies

Akari’s priority pipeline programs remain on track to begin enrollment in the registrational nomacopan Phase 3 clinical trials in pediatric and adult HSCT-TMA and start PAS-nomacopan clinical trials in geographic atrophy (GA)Granted orphan drug designation from the European Commission for treatment in hematopoietic stem cell transplantation, adding to existing FDA Orphan Drug, Fast Track and Rare Pediatric Disease designationsThe company established a Boston U.S. headquarters office to support expanding operations and the start of registrational Phase 3 clinical trialsStrengthened capabilities with appointment of Beth-Anne Lang, an experienced executive with a long track record of successful regulatory approvals, as Senior Vice President, Regulatory Affairs, and industry veterans Wa’el Hashad as independent director and Wendy DiCicco as interim CFO BOSTON and LONDON, Sept. 29, 2023 (GLOBE NEWSWIRE) -- Akari Therapeutics, Plc (Nasdaq: AKTX), a late-stage biotechnology company developing advanced therapies for autoimmune and inflammatory diseases today announced financial results and highlights for the first half of 2023, ended June 30th. Akari’s lead asset, investigational nomacopan, is a bispecific recombinant inhibitor of complement C5 and leukotriene B4 (LTB4). Nomacopan is in Phase 3 development for pediatric hematopoietic stem cell transplant-related thrombotic microangiopathy (HSCT-TMA) and is entering Phase 3 development in adult HSCT-TMA. Long-acting PAS-nomacopan is in final pre-clinical development and is advancing toward clinical trials in geographic atrophy (GA). “I’m delighted our Akari team continues to make steady progress on our ambitions for investors and the patients who are waiting with urgent unmet needs,” said Rachelle Jacques, Akari President and CEO. “We believe we are building strong momentum as we prepare for the start of enrollment in the registrational portion of our nomacopan pediatric and adult Phase 3 clinical trials in HSCT-TMA and move our PAS-nomacopan geographic atrophy development program toward clinical trials.” HSCT-TMA Akari remains on track to start enrollment by the end of 2023 in the registrational Phase 3 study of nomacopan in pediatric HSCT-TMA, which is expected to generate safety and efficacy data that may support U.S. and European regulatory filings for potential marketing authorization in these regions. Consensus guidelines were published in early 2023 by an international panel of experts that harmonize diagnostic criteria and support earlier screening and diagnosis in the care of patients. The design of Akari’s HSCT-TMA Phase 3 clinical trials has been significantly informed by these consensus criteria for earlier diagnosis of high-risk (severe) patients. Adult study design will be an important topic of discussion during a Type C meeting with the U.S. Food and Drug Administration (FDA) scheduled for November 15, 2023. A case study, Clinical Response to Nomacopan in the Paediatric HSCT-TMA Setting, was presented as a late-breaker at The Transplantation & Cellular Therapy Tandem Meetings in February 2023 and as a poster in April 2023 at The European Society for Blood and Marrow Transplantation (EBMT). A 6-year-old male HSCT-TMA patient at Royal Manchester Children’s Hospital, Manchester University NHS Foundation Trust in Manchester, United Kingdom was enrolled in the nomacopan Phase 3 Part A clinical trial, treated with nomacopan and discharged home from the hospital. Akari was granted orphan drug designation from the European Commission for treatment in hematopoietic stem cell transplantation. This designation is an important addition to the FDA Orphan Drug, Fast Track and Rare Pediatric Disease designations for nomacopan for the treatment of pediatric HSCT-TMA. With the Rare Pediatric Disease Designation, Akari is eligible to receive a Priority Review Voucher (PRV) upon approval that it can either redeem for priority review of a subsequent marketing application for a different product or sell to a third party. Akari is also moving forward into a registrational Phase 3 double-blind placebo-controlled clinical trial of nomacopan in adult HSCT-TMA with enrollment expected to begin in 2024 (subject to funding). Regulatory authorities in Poland (Office for Registration of Medicinal Products, Medical Devices and Biocidal Products/URPL) and the U.K. (Medicines & Healthcare products Regulatory Agency/MHRA) approved amendments to the company’s Investigational Medicinal Product Dossier (IMPD) and Clinical Trial Authorization (CTA), respectively, for clinical use of the third-generation drug substance manufacturing process that increases the final yield of nomacopan by at least 5-fold. Geographic Atrophy (GA) Akari completed evaluation of long-acting PAS-nomacopan candidates and based on extensive pre-clinical work selected a single drug candidate to move forward into clinical trials for treatment of GA. The selected version has a product profile with characteristics important for a GA therapy, including fully active drug potency, planned small (<100µL) injection volume, viscosity enabling intravitreal injection with a fine needle, and pre-clinical half-life that supports a potential clinical dose interval of 3 months or longer. Akari also selected Wacker Biotech GmbH as the manufacturing partner to support production of PAS-nomacopan for use in clinical trials. The company remains on track for an Investigational New Drug (IND) submission to the FDA in the first half of 2024 and the start of clinical trials in the second half of 2024 (subject to funding). In May, Akari hosted a key opinion leader event featuring Elias Reichel, M.D., Professor of Ophthalmology at the Tufts University School of Medicine. At the event, Dr. Reichel discussed disease pathology and the need to reduce frequency of intravitreal injections and prevent sight-threatening choroidal neovascularization (CNV) risk in the treatment of GA. At that event, Akari management presented a progress update on the final stages pre-clinical development of long-acting PAS-nomacopan as a potential treatment for GA and the status of clinical trials. Other Highlights As Akari approaches the start of registrational Phase 3 clinical trials in pediatric and adult HSCT-TMA and a regulatory filing to begin clinical trials in GA, the company will be assisted by Beth-Anne Lang, who was appointed as Senior Vice President, Regulatory Affairs in August 2023. Ms. Lang has more than 20 years of experience in regulatory strategy, regulatory affairs, and drug development, and a long track record of successful drug approvals in the U.S. and rest of world. The U.S. industry capabilities of Akari’s Board of Directors was strengthened with the appointment of industry veteran Wa’el Hashad as an independent director. Mr. Hashad brings more than 35 years of biopharmaceutical experience to the Akari Board of Directors with deep experience in drug approvals and commercialization, mergers and acquisitions, and business development. Akari appointed experienced life sciences executive Wendy DiCicco as interim Chief Financial Officer (CFO). Ms. DiCicco has more than 25 years of experience in the life sciences industry, serving as an independent financial and board advisor to companies, often in the role of interim CFO. The company established a Boston Seaport area office that is the Akari U.S. headquarters. The office will support the company’s operations in preparation for the start of registrational nomacopan Phase 3 clinical trials. Akari continues to secure IP for lead asset nomacopan in pipeline programs beyond current priority programs in preparation for future development by the company, licensing or partnering. In April 2023, the European Patent Office granted a patent for nomacopan in the treatment of autoimmune blistering diseases (including bullous pemphigoid). After requesting and being granted a 180-day extension by Nasdaq to meet Nasdaq’s minimum bid price requirement, the company regained compliance in August 2023 and the matter is now closed. Akari’s American Depository Shares (ADSs) continue to trade on the Nasdaq Capital Market under the symbol AKTX. As Akari continues to build out the capabilities, presence, and investor base in the U.S., it has qualified for domestic issuer status with the U.S. Securities and Exchange Commission (SEC) and will begin reporting as a domestic filer effective January 1, 2024. First Half of 2023 Financial Results As of June 30, 2023, the company had cash of approximately $7.2 million. Following the end of the first half 2023, Akari received a United Kingdom (U.K.) research and development tax credit in the amount of $2.5 million and entered into definitive purchase agreements for the sale in a private placement of 551,816 ADSs and pre-funded warrants to purchase up to 48,387 ADSs, which upon closing is expected to result in gross proceeds of approximately $2.0 million. Closing is expected to occur during the first week of October. Existing cash, which assumes closing of the proceeds from the private placement, is expected to be sufficient to fund operations into the first quarter of 2024. Research and development expenses were approximately $3.3 million for the six months ended June 30, 2023, as compared to approximately $5.0 million for the same period in 2022. General and administrative expenses were approximately $6.0 million for the six months ended June 30, 2023, as compared to approximately $6.1 million for the same period in 2022. Total other income was approximately $6.2 million for the six months ended June 30, 2023, as compared to approximately $0.2 million for the same period in 2022. Net loss was approximately $3.0 million for the six months ended June 30, 2023, as compared to net loss of approximately $10.9 million for the same period in 2022. Excluding the non-cash gain of approximately $6.1 million for the six months ended June 30, 2023 related to the change in fair value of warrant liability, net loss was $9.1 million. About Akari Therapeutics Akari Therapeutics, plc (Nasdaq: AKTX) is a biotechnology company developing advanced therapies for autoimmune and inflammatory diseases. Akari’s lead asset, investigational nomacopan, is a bispecific recombinant inhibitor of complement C5 activation and leukotriene B4 (LTB4) activity. Akari’s pipeline includes a Phase 3 clinical trial program investigating nomacopan for severe pediatric hematopoietic stem cell transplant-related thrombotic microangiopathy (HSCT-TMA). Akari has been granted Orphan Drug, Fast Track and Rare Pediatric Disease designations from the FDA for nomacopan for the treatment of pediatric HSCT-TMA and orphan drug designation from the European Commission for treatment in hematopoietic stem cell transplantation. Akari’s pipeline also includes a clinical program developing nomacopan for adult HSCT-TMA and pre-clinical research of long-acting PAS-nomacopan in geographic atrophy (GA). For more information about Akari, please visit akaritx.com. Cautionary Note Regarding Forward-Looking Statements Certain statements in this press release constitute “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995 regarding, among other things, our product development efforts, business, financial condition, results of operations, strategies or prospects and statements related to the offering of securities described herein, the expected gross proceeds and the expected closing of the offering. These forward-looking statements reflect our current views about our plans, intentions, expectations, strategies, and prospects, which are based on the information currently available to us and on assumptions we have made. Although we believe that our plans, intentions, expectations, strategies, and prospects as reflected in or suggested by those forward-looking statements are reasonable, we can give no assurance that the plans, intentions, expectations, or strategies will be attained or achieved. Furthermore, actual results may differ materially from those described in the forward-looking statements and will be affected by a variety of risks and factors that are beyond our control. Such risks and uncertainties for our company include, but are not limited to: needs for additional capital to fund our operations, our ability to continue as a going concern; uncertainties of cash flows and inability to meet working capital needs; an inability or delay in obtaining required regulatory approvals for nomacopan and any other product candidates, which may result in unexpected cost expenditures; our ability to obtain orphan drug designation in additional indications; risks inherent in drug development in general; uncertainties in obtaining successful clinical results for nomacopan and any other product candidates and unexpected costs that may result there; difficulties enrolling patients in our clinical trials; failure to realize any value of nomacopan and any other product candidates developed and being developed in light of inherent risks and difficulties involved in successfully bringing product candidates to market; inability to develop new product candidates and support existing product candidates; the approval by the FDA and EMA and any other similar foreign regulatory authorities of other competing or superior products brought to market; risks resulting from unforeseen side effects; risk that the market for nomacopan may not be as large as expected risks associated with the impact of the COVID-19 pandemic; inability to obtain, maintain and enforce patents and other intellectual property rights or the unexpected costs associated with such enforcement or litigation; inability to obtain and maintain commercial manufacturing arrangements with third party manufacturers or establish commercial scale manufacturing capabilities; the inability to timely source adequate supply of our active pharmaceutical ingredients from third party manufacturers on whom the company depends; unexpected cost increases and pricing pressures and risks and other risk factors detailed in our public filings with the U.S. Securities and Exchange Commission, including our most recently filed Annual Report on Form 20-F filed with the SEC. Except as otherwise noted, these forward-looking statements speak only as of the date of this press release and we undertake no obligation to update or revise any of these statements to reflect events or circumstances occurring after this press release. We caution investors not to place considerable reliance on the forward-looking statements contained in this press release. Akari Therapeutics Plc Condensed Consolidated Statements of Operations and Comprehensive Loss(Unaudited, in U.S. dollars) Six Months Ended June 30, 2023 2022 Operating expenses: Research and development expenses$3,255,221 $4,990,715 General and administrative expenses 5,954,379 6,069,422 Total operating expenses 9,209,600 11,060,137 Loss from operations (9,209,600) (11,060,137) Other income: Interest income 59,091 8,317 Change in fair value of warrant liability 6,147,210 — Foreign currency exchange gain 27,516 211,761 Other expenses (22,825) (16,314)Total other income, net 6,210,992 203,764 Net loss$(2,998,608) $(10,856,373) Net loss per ordinary share, basic and diluted$(0.00) $(0.00)Weighted average ordinary shares outstanding — basic and diluted 8,787,337,361 5,648,226,680 Comprehensive loss: Net loss$(2,998,608) $(10,856,373)Other comprehensive loss: Foreign currency translation adjustment (55,038) (80,590)Total comprehensive loss$(3,053,646) $(10,936,963) Akari Therapeutics Plc Consolidated Balance Sheet Data(Unaudited, in U.S. dollars) June 30, December 31, 2023 2022Cash$7,180,688 $13,249,945 Other assets 832,283 581,667 Total assets$8,012,971 $13,831,612 Total liabilities$5,231,514 $12,040,866 Total shareholders’ equity 2,781,457 1,790,746 Total liabilities and shareholders’ equity$8,012,971 $13,831,612 For more information Investor Contact:Mike MoyerLifeSci Advisors(617) 308-4306mmoyer@lifesciadvisors.com Media Contact:Eliza SchleifsteinSchleifstein PR (917) 763-8106eliza@schleifsteinpr.com