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AstraZeneca has terminated all development of vemircopan, the oral factor D inhibitor it acquired through the deal for Alexion in 2021. The UK major recorded an impairment charge of $753 million as a result, according to 2024 earnings that were reported on Thursday. Development of vemircopan for paroxysmal nocturnal hemoglobinuria was halted in November 2023, but now the drug is being abandoned completely. A Phase 2 trial in lupus nephritis or IgA nephropathy, and an early-stage trial in impaired hepatic function, have also been discontinued for lack of efficacy. Marc Dunoyer, the CEO of AstraZeneca’s rare disease unit, said it “is not immune to the odds of the industry, where not all of the pioneering work that you do is going to work.” He added that the decision to drop vemircopan was based on standard criteria, namely its benefits and risks, as well as the competitive situation. Despite the loss, AstraZeneca CEO Pascal Soriot told reporters at a London event: “I can say with no hesitation, the Alexion acquisition was a fantastic acquisition.” AstraZeneca also took a $165 million impairment on FPI-2059, a Phase 1-stage radioligand that was scrapped. The drug was part of last year’s purchase of Fusion Pharmaceuticals. FPI-2059 is a lutetium-labeled small molecule targeting neurotensin receptor 1 which Alexion itself licensed from Ipsen in 2021. Other radioligands remain in development. AstraZeneca’s lead radioconjugate, FPI-2265, is a beta-emitting, PSMA-targeting product. Data on its Phase 2 prostate cancer trial could come in the second half of this year. “The field of radioconjugates is a little behind the field of ADCs at the moment, but it holds great potential,” AstraZeneca’s oncology R&D leader Susan Galbraith said at the earnings event. Elsewhere, AstraZeneca shut down: The company also reiterated the termination of a mid-stage study of an orexin 1 receptor antagonist, AZD4041, in opioid use disorder. The shuttering emerged in November , with a spokesperson telling Endpoints News the move was due to “a potential drug-drug interaction.” It appears that AstraZeneca will put its long-acting amylin asset AZD6234 into a new Phase 2b trial in obesity, in combination with the GLP-1/glucagon agonist AZD9550. According to a record on the EU’s trial database , the trial will end in the middle of next year. AZD6234 is already in a separate mid-stage monotherapy trial, which could yield data late this year. The company claimed it is heading into an “unprecedented catalyst-rich 2025,” citing a handful of late-stage trials for indication expansions, such as the AVANZAR study of Datroway in first-line non-small cell lung cancer. David Fredrickson, the leader of the company’s oncology business, affirmed his confidence in the ADC despite its stumbles in late-stage trials in both lung and breast cancers. “We’ve been able to apply the lessons that we’ve learned from the previous Phase 3 and Phase 2 studies that have read out so far to the frontline AVANZAR study,” Fredrickson said. The trial is enriched for the non-squamous population “because we think that’s the opportunity to see the most benefit for Datroway in the front line.” Combining the drug with the checkpoint inhibitor Imfinzi could also increase the chances of success, he said. Other major Phase 3 readouts will come for products still in earlier stages, such as the SERD camizestrant in breast cancer, baxdrostat in hypertension, and eneboparatide in hypoparathyroidism.

Data demonstrate NurOwn's safety and provide preliminary evidence of efficacy in patients with progressive multiple sclerosis Biomarker analyses show consistent treatment effects in neuroinflammation and neuroprotection pathways NEW YORK, Sept. 15, 2022 /PRNewswire/ -- BrainStorm Cell Therapeutics Inc. (NASDAQ: BCLI), a leading developer of cellular therapies for neurodegenerative diseases, today announced the peer reviewed publication of data from the Phase 2 trial of NurOwn in progressive multiple sclerosis (MS) in Multiple Sclerosis Journal. The publication, entitled "Evaluation of neurotrophic factor secreting mesenchymal stem cells in progressive multiple sclerosis", can be found here. Results from the Phase 2, single-arm, open-label study demonstrated NurOwn's safety and provided preliminary evidence of its efficacy in people with progressive MS. Additionally, biomarker analyses confirmed NurOwn's proposed mechanism of action by showing consistent treatment effects in neuroinflammation and neuroprotection pathways. Twenty participants were enrolled into the Phase 2 trial, with seventeen receiving all three scheduled NurOwn treatments. The mean age of study participants was 47 years with a mean expanded disability status scale (EDSS) score of 5.4 at screening. Results from the trial were compared to 48 matched control patients who were selected from the from the Comprehensive Longitudinal Investigation of Multiple Sclerosis (CLIMB) registry (Brigham and Women's Hospital and the Ann Romney Center for Neurologic Diseases) at the beginning of the trial. Treatment with NurOwn resulted in large, clinically meaningful improvements in some patients, as defined by response criteria, across all endpoints measured. These endpoints included timed 25-foot walk speed (T25FW), 9-hole peg test (9HPT), multiple sclerosis walking scale (MSWS), symbol digit modality test (SDMT), and low contrast letter acuity (LCLA). These observed improvements diverged from what was seen in matched patients with progressive MS from the CLIMB registry. Key data from the trial, as well as relevant comparisons to the matched CLIMB registry patients, are shown below. 19% of treated trial participants were responders (as defined by prespecified ≥25% improvement in T25FW or 9HPT at 28 weeks compared to baseline), compared to 4% of the matched CLIMB registry patients. 38% of treated trial participants showed a ≥10-point improvement from baseline in the 12-item MSWS (data for this endpoint were not collected by the CLIMB registry). 27% of treated trial participants showed a ≥8-letter improvement in LCLA binocular at a 2.5% contrast threshold, compared to 6% of the matched CLIMB registry patients. 67% of treated trial participants showed a ≥3-point improvement in the SDMT, compared to 18% of the matched CLIMB registry patients. 47% of treated trial participants showed a ≥8-point improvement in LCLA binocular at a 1.25% contrast threshold (data for this endpoint were not collected by the CLIMB registry). Across all participants, improvements in function as measured by LCLA, SDMT and MS Functional Composite (MSFC) were observed. Mean improvements from baseline of 3.3 points in the LCLA binocular (2.5% contrast), 3.8 points on the SDMT, and 0.18 points in MSFC were observed in treated trial participants. The corresponding changes in matched CLIMB registry patients estimated at 28 weeks showed declines in function on the LCLA and MSFC. The average change in function decline as measured by T25FW, 9HPT, and EDSS across all treated trial participants demonstrated stabilization of functional decline, with similar or slightly worse findings observed in the matched CLIMB registry patients for the same endpoints. There were no adverse events related to worsening of MS disease and no clinically significant changes in safety lab results/vital signs, confirming NurOwn's favorable safety profile. Two patients developed symptoms of low back and leg pain, consistent with arachnoiditis, occurring in one of three treatments in both participants. Treatment also consistently resulted in increases in cerebrospinal fluid neuroprotective factors (VEGF–A, HGF, NCAM-1, Follistatin, LIF and Fetuin–A) and reductions in inflammatory biomarkers (MCP-1, sCD27, SDF-1, and Osteopontin), confirming NurOwn's proposed mechanism of action in progressive MS. "We were pleased that the study's initial results showed efficacy in patients with progressive MS," said Jeffrey Cohen, M.D., Hazel Prior Hostetler Endowed Chair Professor, Cleveland Clinic Lerner College of Medicine, Director, Experimental Therapeutics, Mellen Center for MS Treatment and Research, and the paper's lead author. "There are both promising biological and preliminary clinical signals of a treatment effect that will require confirmation in a randomized trial." "There is a high unmet need for better treatments for progressive forms of MS and we congratulate the Brainstorm Cell Therapeutics team for the successful completion and publication of this important study. We look forward to future studies that will help to fully understand the potential of NurOwn and other cell-based therapies for this hard-to-treat form of disease" said Bruce Bebo, EVP Research National MS Society. Chaim Lebovits, Chief Executive Officer, BrainStorm Cell Therapeutics stated, "Having these data peer reviewed and published in the prestigious Multiple Sclerosis Journal is an important step in the evaluation of NurOwn in progressive MS. We appreciate the expertise and commitment of the study investigators and contributions of study participants to advance our understanding of NurOwn's cellular technology platform. Thanks to their efforts and those of the BrainStorm team, we believe we are closer to providing a meaningful treatment option for those with progressive MS". Ralph Kern, M.D., MHSc, President and Chief Medical Officer of BrainStorm Cell Therapeutics and co-author of the paper commented, "This publication provides preliminary evidence of NurOwn's potential to modify functional outcomes in progressive MS, which we believe warrants further study. In addition, consistent changes in cerebrospinal fluid neuroinflammation and neuroprotection biomarkers reveal how NurOwn may impact disease mechanisms in progressive MS and are complementary to biomarker results observed in our Phase 3 ALS trial. These observations provide further support for NurOwn as a platform technology with potential broad applications and will bolster BrainStorm's efforts to bring much needed solutions to patients with progressive MS, ALS, and other neurodegenerative diseases." Study Design The Phase 2 study (BCT-101) was designed to evaluate the safety, efficacy, and biomarker effects of three intrathecal administrations of NurOwn (MSC-NTF cells), given at two-month intervals, to adults with progressive MS. The trial was conducted at four MS centers of excellence: Cleveland Clinic Mellen Center for MS, Icahn School of Medicine at Mount Sinai, Keck School of Medicine of the University of Southern California, and Stanford University School of Medicine. Twenty participants ages 18-65 with progressive MS were enrolled and 17 received all three treatments and were followed for up to 28 weeks. Participants had baseline EDSS scores of between 3.0 and 6.5, were able to walk 25 feet in 60 seconds or less and had not experienced an MS relapse in the 6 months prior to study enrollment. The primary efficacy outcome was pre-specified improvement (≥25%) in T25FW or 9-HPT. Additional efficacy endpoints included pre-specified improvements in EDSS, SDMT, LCLA, and MSWS-12. The efficacy outcomes were compared to a pre-specified matched group of progressive MS patients from CLIMB registry (n=48) (Tanuja Chitnis, M.D. Brigham and Women's Hospital and the Ann Romney Center for Neurologic Diseases). The study was sponsored by Brainstorm Cell Therapeutics with additional financial support for biomarker analyses received from the National Multiple Sclerosis Society, Fast-Forward Commercial Research Funding Program. For more information on the trial, visit . About NurOwn® The NurOwn® technology platform (autologous MSC-NTF cells) represents a promising investigational therapeutic approach to targeting disease pathways important in neurodegenerative disorders. MSC-NTF cells are produced from autologous, bone marrow-derived mesenchymal stem cells (MSCs) that have been expanded and differentiated ex vivo. MSCs are converted into MSC-NTF cells by growing them under patented conditions that induce the cells to secrete high levels of neurotrophic factors (NTFs). Autologous MSC-NTF cells are designed to effectively deliver multiple NTFs and immunomodulatory cytokines directly to the site of damage to elicit a desired biological effect and ultimately slow or stabilize disease progression. About BrainStorm Cell Therapeutics Inc. BrainStorm Cell Therapeutics Inc. is a leading developer of innovative autologous adult stem cell therapeutics for debilitating neurodegenerative diseases. The Company holds the rights to clinical development and commercialization of the NurOwn® technology platform used to produce autologous MSC-NTF cells through an exclusive, worldwide licensing agreement. Autologous MSC-NTF cells have received Orphan Drug designation status from the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for the treatment of amyotrophic lateral sclerosis (ALS). BrainStorm has completed a Phase 3 pivotal trial in ALS (NCT03280056); this trial investigated the safety and efficacy of repeat-administration of autologous MSC-NTF cells and was supported by a grant from the California Institute for Regenerative Medicine (CIRM CLIN2-0989). BrainStorm completed under an investigational new drug application a Phase 2 open-label multicenter trial (NCT03799718) of autologous MSC-NTF cells in progressive MS and was supported by a grant from the National MS Society (NMSS). Safe-Harbor Statement Statements in this announcement other than historical data and information, including statements regarding future clinical trial enrollment and data, constitute "forward-looking statements" and involve risks and uncertainties that could cause BrainStorm Cell Therapeutics Inc.'s actual results to differ materially from those stated or implied by such forward-looking statements. Terms and phrases such as "may," "should," "would," "could," "will," "expect," "likely," "believe," "plan," "estimate," "predict," "potential," and similar terms and phrases are intended to identify these forward-looking statements. The potential risks and uncertainties include, without limitation, BrainStorm's need to raise additional capital, BrainStorm's ability to continue as a going concern, prospects for future regulatory approval of BrainStorm's NurOwn® treatment candidate, the success of BrainStorm's product development programs and research, regulatory and personnel issues, development of a global market for our products and services, the ability to secure and maintain research institutions to conduct our clinical trials, the ability to generate significant revenue, the ability of BrainStorm's NurOwn® treatment candidate to achieve broad acceptance as a treatment option for ALS or other neurodegenerative diseases, BrainStorm's ability to manufacture and commercialize the NurOwn® treatment candidate, obtaining patents that provide meaningful protection, competition and market developments, BrainStorm's ability to protect our intellectual property from infringement by third parties, heath reform legislation, demand for our services, currency exchange rates and product liability claims and litigation; the impacts of the COVID-19 pandemic on our clinical trials, supply chain, and operations; and other factors detailed in BrainStorm's annual report on Form 10-K and quarterly reports on Form 10-Q available at . These factors should be considered carefully, and readers should not place undue reliance on BrainStorm's forward-looking statements. The forward-looking statements contained in this press release are based on the beliefs, expectations, and opinions of management as of the date of this press release. We do not assume any obligation to update forward-looking statements to reflect actual results or assumptions if circumstances or management's beliefs, expectations or opinions should change, unless otherwise required by law. Although we believe that the expectations reflected in the forward-looking statements are reasonable, we cannot guarantee future results, levels of activity, performance, or achievements. CONTACTS Investor Relations: John Mullaly LifeSci Advisors, LLC Phone: +1 617-429-3548 [email protected] Media: Lisa Guiterman [email protected] Logo - SOURCE BrainStorm Cell Therapeutics Inc.

HAMILTON, Bermuda, May 13, 2019 (GLOBE NEWSWIRE) -- Kiniksa Pharmaceuticals, Ltd. (Nasdaq: KNSA) (“Kiniksa”), a biopharmaceutical company focused on discovering, acquiring, developing and commercializing therapeutic medicines for patients with significant unmet medical need, today announced that it presented clinical and preclinical data for KPL-716, an investigational fully-human monoclonal antibody that targets oncostatin M receptor beta (OSMRβ), the shared receptor subunit for interleukin-31 (IL-31) and oncostatin M (OSM) signaling. The data were included in oral and poster presentations at the 77th Annual Meeting of the Society for Investigative Dermatology in Chicago, IL. “We are pleased to grow the body of scientific data on the role of IL-31 and OSM in chronic pruritic conditions,” said Sanj K. Patel, Chief Executive Officer and Chairman of the Board of Kiniksa. “We believe that by simultaneously inhibiting these two key cytokine pathways through targeting a single epitope, OSMRβ, KPL-716 may be a differentiated mechanism for the potential treatment of a spectrum of chronic pruritic diseases. We have initiated a global Phase 2a clinical trial of KPL-716 in subjects with prurigo nodularis and plan to initiate an exploratory Phase 2 clinical trial in diseases characterized by chronic pruritus in the first half of 2019.” The data presentations were as follows: Dr. Zamaneh Mikhak, of Kiniksa Pharmaceuticals Corp., delivered an oral presentation entitled KPL-716, Anti-OSMRβ Antibody, Reduced Pruritus in Atopic Dermatitis. Data from the adjunctive therapy period (Day 29 to Day 60; topical corticosteroids allowed) of Kiniksa’s Phase 1a/1b clinical trial of single-dose KPL-716 7.5 mg/kg intravenous (IV) in subjects with moderate-to-severe atopic dermatitis experiencing moderate-to-severe pruritus versus placebo IV showed a sustained anti-pruritic effect of OSMRβ inhibition through at least week 6. The data reinforce and extend the previously-reported findings from the Phase 1a/1b monotherapy period (Day -7 to Day 28; topical corticosteroids not allowed), which provided evidence of target engagement and an early signal of efficacy in reducing pruritus and disease severity. Dr. John F. Paolini, of Kiniksa Pharmaceuticals Corp., delivered a poster presentation entitled The OSMRβ Axis Identified in Prurigo Nodularis. Data from Kiniksa’s longitudinal observational study in prurigo nodularis (LOTUS-PN) suggest that the OSMRβ axis (IL-31, OSM, IL-31 receptor alpha (IL-31Rα) and OSMRβ) may play a role in the pathogenesis of prurigo nodularis given its prevalent expression in lesional prurigo nodularis. IL-31 messenger ribonucleic acid (mRNA) was expressed in approximately two-thirds of lesional biopsies from prurigo nodularis patients with Worst-Itch Numeric Rating Scale (WI-NRS) ≥ 7 compared to one-tenth in healthy volunteers. Additionally, lesional biopsies from prurigo nodularis patients contained mononuclear cells expressing OSM, OSMRβ, IL-31 and IL-31Rα protein compared with non-lesional biopsies. Dr. Carl D. Richards, of McMaster Immunology Research Centre, delivered an e-poster presentation entitled OSM Induction of Monocyte Chemoattractant Protein 1 (MCP-1) in Human Epidermal Keratinocytes is Inhibited by Anti-OSMRβ Monoclonal Antibody KPL-716. OSM is involved in Type 2 T helper (TH2) inflammation, epidermal integrity and fibrosis. Data highlight the therapeutic potential of KPL-716, through the inhibition of OSM activity, in TH2 mediated diseases discrete from inhibition of IL-31. Further, the data show induction of MCP-1 and mRNA by OSM in both cell types tested and significant attenuation by KPL-716 of the cellular MCP-1 response to OSM and the synergistic response to OSM and interleukin-4 (IL-4). Importantly, these data showed that OSM synergizes with IL-4 and interleukin-13 (IL-13), and that leukemia inhibitory factor (LIF) and IL-31 do not. Dr. Rohan Gandhi, of Kiniksa Pharmaceuticals Corp., delivered a poster presentation entitled KPL-716, an OSMRβ Monoclonal Antibody, Reduces IL-31-Induced Scratching Behavior in Cynomolgus Monkeys: Establishment and Optimization of Pharmacokinetic/Pharmacodynamic Model. KPL-716 data from a preclinical model exhibited dose- and time-dependent anti-pruritic effects. Pharmacokinetic (PK) and Pharmacodynamic (PD) correlation established an efficacious concentration range of 5 – 8.5 μg/ml in cynomolgus monkeys, at or above which KPL-716 provided protection from pruritus induced by supra-physiologic challenges of IL-31. The results with single dose KPL-716 IV were corroborated with repeat-dosed KPL-716 subcutaneous in various dosing regimens and were predictive of the reduction in pruritus observed in the Phase 1a/1b clinical trial of single-dose KPL-716 7.5 mg/kg IV in subjects with moderate-to-severe atopic dermatitis experiencing moderate-to-severe pruritis. The materials are available through the Investors and Media section of Kiniksa’s website (www.kiniksa.com). About KPL-716 KPL-716 is an investigational fully-human monoclonal antibody that targets OSMRβ, which mediates signaling of IL-31 and OSM, two key cytokines implicated in pruritus, inflammation and fibrosis. Kiniksa believes KPL-716 to be the only monoclonal antibody in development that targets both pathways simultaneously. About Kiniksa Kiniksa is a biopharmaceutical company focused on discovering, acquiring, developing and commercializing therapeutic medicines for patients suffering from debilitating diseases with significant unmet medical need. Kiniksa has a pipeline of product candidates across various stages of development, focused on autoinflammatory and autoimmune conditions. For more information, please visit www.kiniksa.com. Forward-Looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. In some cases, you can identify forward looking statements by terms such as “may,” “will,” “should,” “expect,” “plan,” “anticipate,” “could,” “intend,” “target,” “project,” “contemplate,” “believe,” “estimate,” “predict,” “potential” or “continue” or the negative of these terms or other similar expressions, although not all forward‑looking statements contain these identifying words. All statements contained in this press release that do not relate to matters of historical fact should be considered forward-looking statements, including without limitation, statements regarding: our belief of the potential for KPL-716 to be a differentiated mechanism for the potential treatment of a spectrum of chronic pruritic diseases; our plans and timing to commence an exploratory Phase 2 clinical trial of KPL-716; and our conclusions from interim pre-clinical and clinical trial data for KPL-716. These forward-looking statements are based on management’s current expectations. These statements are neither promises nor guarantees, but involve known and unknown risks, uncertainties and other important factors that may cause our actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements, including without limitation, the following: changes between final data and any interim data we present; our potential inability to replicate in later clinical trials, including our Phase 2a clinical trial and planned exploratory Phase 2 clinical trial of KPL-716, the positive interim data from our pre-clinical and earlier clinical trials; potential impact of additional data from us or other companies; potential undesirable side effects caused by KPL-716; our potential inability to demonstrate safety and efficacy to the satisfaction of applicable regulatory authorities; and our reliance on third parties to manufacture KPL-716 and to conduct research, clinical trials and/or certain regulatory activities for KPL-716. These and other important factors discussed under the caption “Risk Factors” in our Quarterly Report on Form 10-Q for the period ended March 31, 2019, filed with the Securities and Exchange Commission (“SEC”) on May 7, 2019, and our other reports filed with the SEC, could cause actual results to differ materially from those indicated by the forward-looking statements made in this press release. Any such forward-looking statements represent management’s estimates as of the date of this press release. While we may elect to update such forward-looking statements at some point in the future, we disclaim any obligation to do so, even if subsequent events cause our views to change. These forward-looking statements should not be relied upon as representing our views as of any date subsequent to the date of this press release. Every Second Counts!™ Kiniksa Investor and Media Contact Mark Ragosa (781) 430-8289 mragosa@kiniksa.com Source: Kiniksa Pharmaceuticals, Ltd.