Germans Trias I Pujol

In Phase 2 ALPACA results, lepodisiran significantly reduced levels of genetically inherited cardiovascular risk factor, with some patients sustaining reductions for nearly 1.5 years These data were presented at the American College of Cardiology 2025 Scientific Sessions and simultaneously published in the New England Journal of Medicine (NEJM) INDIANAPOLIS, IN, USA I March 30, 2025 I Eli Lilly and Company (NYSE: LLY) today announced positive Phase 2 results for lepodisiran, an investigational small interfering RNA (siRNA) therapy designed to lower the production of lipoprotein(a) [Lp(a)], a genetically inherited risk factor for heart disease. In the Phase 2 ALPACA study, lepodisiran significantly reduced Lp(a) levels by an average of 93.9% over the 60 to 180-day period after treatment with the highest tested dose (400 mg), meeting the primary endpoint. i Participants who received the 16 mg and 96 mg lepodisiran doses experienced a 40.8% reduction and a 75.2% reduction in Lp(a) levels over the same time period, respectively. i Lepodisiran also met additional secondary endpoints, showing reductions in Lp(a) levels following one or two administrations of each of the three tested doses across all timepoints assessed throughout the nearly 18-month-long study. ii Lepodisiran was administered twice at each dose (16 mg, 96 mg, or 400 mg), once at baseline and at day 180, with a separate group receiving 400 mg at baseline and placebo at day 180. The effect of additional doses of lepodisiran remains undetermined. “Nearly a quarter of the world’s population has elevated levels of Lp(a), putting them at a significantly higher risk of cardiovascular events such as heart attacks and strokes. Unfortunately, there are no approved cholesterol-lowering therapies specifically for this genetic risk factor, and lifestyle changes like diet and exercise do not provide meaningful reductions,” said Steven Nissen, M.D., chief academic officer of the Heart, Vascular & Thoracic Institute at the Cleveland Clinic. “These significant and sustained Lp(a) reductions are encouraging and suggest that siRNA approaches like lepodisiran could potentially offer durable benefits with long-term dosing.” About 20% of Americans have high levels of Lp(a), which increases their risk of cardiovascular disease. 1,2 Elevated Lp(a) levels can double or even triple the risk of a heart attack and are associated with other cardiovascular issues such as stroke and heart valve narrowing (aortic valve stenosis). 3,4,5 Lepodisiran is an investigational siRNA therapy designed to reduce levels of Lp(a) by inhibiting the production of apolipoprotein(a) (apo[a]), a key component of Lp(a). “Reducing the inherited cardiovascular risk for patients with high Lp(a) has long been a critically unmet need. These results offer hope for a long-term, durable treatment option,” said Ruth Gimeno, group vice president, diabetes, obesity and cardiometabolic research at Lilly. “These data underscore Lilly’s commitment to advancing genetic medicine to address one of the world’s most pressing healthcare challenges. We will continue to evaluate the potential benefits of lepodisiran in the ongoing Phase 3 cardiovascular outcomes trial.” Results from additional secondary endpoints showed: Treatment-emergent adverse events (TEAEs) related to the study drug occurred in 1% (1/69) of the placebo group, 3% (1/36) of the 16 mg group, 12% (9/74) of the 96 mg group and 14% (20/141) of the pooled 400 mg group. There were no serious adverse events related to lepodisiran treatment. A single death occurred in the 16 mg dose group due to complications of chronic coronary disease. One participant in the placebo group was withdrawn from the study drug due to a TEAE; however, no participants receiving lepodisiran experienced a TEAE leading to withdrawal from treatment or the study. The ACCLAIM-Lp(a) Phase 3 clinical development program, investigating the effect of lepodisiran on the reduction of cardiovascular events in adults with elevated Lp(a), is currently enrolling. About ALPACA ALPACA was a randomized, double-blind, placebo-controlled Phase 2 study designed to investigate the efficacy and safety of lepodisiran in adults with elevated Lp(a). A total of 320 participants were randomized to receive either placebo or one of three doses of lepodisiran (16 mg, 96 mg, or 400 mg) both at baseline and day 180. An additional group received 400 mg of lepodisiran at baseline and placebo at day 180. Results from the two groups receiving 400 mg of lepodisiran were pooled for the primary analysis. The primary endpoint was placebo-adjusted, time-averaged percent change in Lp(a) serum concentration from day 60 to 180. About Lilly Lilly is a medicine company turning science into healing to make life better for people around the world. We’ve been pioneering life-changing discoveries for nearly 150 years, and today our medicines help tens of millions of people across the globe. Harnessing the power of biotechnology, chemistry and genetic medicine, our scientists are urgently advancing new discoveries to solve some of the world’s most significant health challenges: redefining diabetes care; treating obesity and curtailing its most devastating long-term effects; advancing the fight against Alzheimer’s disease; providing solutions to some of the most debilitating immune system disorders; and transforming the most difficult-to-treat cancers into manageable diseases. With each step toward a healthier world, we’re motivated by one thing: making life better for millions more people. That includes delivering innovative clinical trials that reflect the diversity of our world and working to ensure our medicines are accessible and affordable. To learn more, visit Lilly.com and Lilly.com/news , or follow us on Facebook , Instagram , and LinkedIn . P-LLY Trademarks and Trade Names All trademarks or trade names referred to in this press release are the property of the company, or, to the extent trademarks or trade names belonging to other companies are references in this press release, the property of their respective owners. Solely for convenience, the trademarks and trade names in this press release are referred to without the ® and ™ symbols, but such references should not be construed as any indicator that the company or, to the extent applicable, their respective owners will not assert, to the fullest extent under applicable law, the company’s or their rights thereto. We do not intend the use or display of other companies’ trademarks and trade names to imply a relationship with, or endorsement or sponsorship of us by, any other companies. i Placebo-adjusted values based on the treatment-regimen estimand. ii Placebo-adjusted values based on the efficacy estimand, which represents efficacy prior to discontinuation of study drug or initiation of medications known to affect lipoprotein(a). References SOURCE: Ell Lilly

Researchers have recently shown that vitamin C improves the immunogenic properties of dendritic cells, in vitro. Results recently made public show that treating the cells with vitamin C leads to a more consistent activation of genes involved in the immune response, mainly through DNA demethylation, a kind of epigenetic reprogramming. This discovery may be useful to generate more potent dendritic cell-based therapies in the future. Researchers from the Epigenetics and Immune Disease Lab at the Josep Carreras Leukaemia Research Institute have recently shown that vitamin C improves the immunogenic properties of dendritic cells, in vitro. Results recently made public show that treating the cells with vitamin C leads to a more consistent activation of genes involved in the immune response, mainly through DNA demethylation, a kind of epigenetic reprogramming. This discovery may be useful to generate more potent dendritic cell-based therapies in the future. Since the onset of anticancer cell therapies, those that use living cells to find and eliminate tumors, many types of immune cells have been used. The best-known cell therapies use lymphocytes, as in the highly successful CAR-T therapies. Recently, dendritic cells have attracted the scientists' attention thanks to its ability to uptake and present antigens (small parts of a pathogen or a cancer cell) to the T-lymphocytes and induce an antigen-specific potent immune activation. On this regard, loading dendritic cells with specific antigens to create immune memory constitute the so-called DC-vaccines. To study dendritic cells in the lab, researchers differentiate them from monocytes (also an immune cell) using a particular set of molecular signaling. This differentiation is accomplished through a complex set of gene activation processes in the nucleus, mostly thanks to the activity of the chromatin remodeling machinery spearheaded by the TET family of demethylases, proteins that act upon the DNA epigenetic marks. Vitamin C was known to interact with several TET proteins to enhance its activity, but the specific mechanism was still poorly understood in human cells. In a recent publication in the journal Nucleic Acids Research, a team lead by Dr. Esteban Ballestar hypothesized that treating monocytes in vitro while differentiating into dendritic cells, would help the resulting cells be more mature and active. The results obtained by Octavio Morante-Palacios, first author of the publication, José Luis Sardina (also from the Josep Carreras Leukaemia Research Institute) and Eva Martínez-Cáceres, Head of Immunology of the Germans Trias i Pujol Research Institute, show that vitamin C treatment triggers an extensive demethylation at NF- kB/p65 binding sites compared with non-treated cells, promoting the activity of genes involved in antigen presentation and immune response activation. Also, vitamin C increases the communication of the resulting dendritic cells with other components of the immune system and stimulates the proliferation of antigen-specific T cells. Actually, the researchers proved that vitamin C-stimulated dendritic cells loaded with antigens specific for the SARS-CoV-2 virus were able to activate T cells in vitro more efficiently than non-treated cells, showing the superiority of DC-vaccines treated with vitamin C. Overall, these new findings support the hypothesis that treating monocyte-derived dendritic cells with vitamin C may help generate DC-vaccines with higher performance. After consolidating these results in preclinical models and, hopefully, in clinical trials, a new generation of cell therapies based on dendritic cells may be used in the clinic to fight cancer more efficiently.

Reinforced cash position finances operations through key clinical milestones to mid-2019, phase IIb clinical programs for ABX464 in HIV and IBD patients expected to be initiated around end of 2018. 2017 Full-Year Results and Progress Report Reinforced cash position finances operations through key clinical milestones to mid-2019 Phase IIb clinical programs for ABX464 in HIV and IBD patients expected to be initiated around end of 2018 HIGHLIGHTS of 2017 HIV : first ever reduction of HIV reservoir in patients’ blood observed in two independent ABX464 Phase IIa trials Ulcerative colitis : phase IIa proof-of-concept clinical trial on track with over half (16/30) of the patients recruited and the first patient already enrolled in the one year open-label extension study ABX464’s novel mechanism of action further elucidated Cancer : promising ABX196 preclinical results showing the immune enhancer’s effects in hepatocellular cancer (HCC) Antivirals (RSV, influenza, Dengue): ABIVAX’s proprietary antiviral discovery platform yielded promising new compounds targeting Respiratory Syncytial Virus (RSV), influenza and all serotypes of Dengue Total cash employed for operations was €12m and net cash consumption, after Bpifrance funding and research tax credit, was €6m in 2017, resulting in a €17m cash position as of December 31, 2017 Paris, March 16, 2018 at 8:30am CET – ABIVAX (Euronext Paris: FR0012333284 – ABVX), an innovative biotechnology company targeting the immune system to develop treatments for viral and inflammatory diseases, and cancer, today announced its 2017 full year financial results, as of December 31 st , and provided an update on its progress, as well as its outlook for 2018. The audited financial statements for 2017 were approved by the Company’s Board of Directors on March 15, 2018. The certification report is being prepared by the Company’s external auditors. “2017 was an exciting year for ABIVAX, witnessing strong progress both in the development of our portfolio as well as from a financial perspective ,” said Professor Hartmut Ehrlich, M.D., Chief Executive Officer of ABIVAX . “ABX464, the company’s most advanced therapeutic candidate, has shown in two separate clinical trials that it reduces the HIV viral reservoir by up to 50% after only one month of treatment. These data clearly validate ABX464 as a key component of a potential functional cure in HIV patients. Top-line data after longer-term 3-month treatment are expected in mid-2018 and, at around the same time, we anticipate filing the requests for regulatory authorizations in U.S. and Europe to start phase IIb testing of ABX464 in HIV patients. These data and plans forward substantiate the commitment of ABIVAX to improve the life of people with HIV.” Dr. Ehrlich continued: “ Also, we are making excellent progress with our phase IIa POC clinical trial of ABX464 in patients with ulcerative colitis, which is halfway enrolled and expected to deliver top-line data during the second half of 2018, with initiation of phase IIb IBD testing scheduled for around the end of 2018.” “Finally, we secured additional financing extending our financial resources for at least one additional year, enabling us to fund all planned activities until mid-2019,” added Dr. Ehrlich. 2017 OPERATING HIGHLIGHTS Strategic business focus: Leverage proprietary technologies to discover and develop new therapeutic candidates targeting the human immune system ABIVAX develops antivirals and immunotherapies that originate from three proprietary technology platforms: “Antiviral , ” based on technologies jointly developed with the National Center for Scientific Research (CNRS) in Montpellier, France, and the Curie Institute in Orsay, France. This platform has generated a highly targeted chemical library of more than 1200 compounds that block viral replication due to completely new modes of action, i.e. the modulation of mRNA biogenesis. The relevance of this platform is exemplified by ABX464, which to date has been administered to more than 170 subjects and has been shown to be safe and well tolerated, with heretofore unobserved activity in reducing the HIV viral reservoirs in patients, as well as viral load. In addition to ABX464, this platform has generated various molecules targeting other viruseinfluenza and all four serotypes of the Dengue virus. ABIVAX is developing these novel molecules, which are currently in hit-to-lead stage, in collaboration with EVOTEC, a global leading contract research organization, with the goal to start lead optimization for the first molecule (an antiviral against RSV) by the end of this year. “Immune enhancer,” based on an intellectual property licensed from the Scripps Research Institute (La Jolla, CA, United States). It focuses on invariant natural killer T cells (or iNKT) agonists, which have been shown to stimulate both humoral and cellular immune responses and may have clinical applications in both infectious diseases and oncology. Following encouraging results of the lead immune enhancer compound ABX196 in preclinical testing in several cancer models, as well as Phase I clinical testing in human volunteers, ABIVAX is now preparing for a POC phase I/II clinical trial in HCC, which is expected to start around year-end 2018. “Polyclonal antibodies,” which leads to the generation of neutralizing antibodies for the prevention and treatment of Ebola virus infections. ABX544 is currently in preclinical development, and ABIVAX will review the next steps depending on results of ongoing studies. Pipeline update ABX464, a potential key element for a functional HIV cure During the past two decades, antiretroviral treatments have turned HIV from a lethal into a chronic disease, at least in developed countries. Currently, there are approximately 37 million people living with HIV, resulting in global sales of pharmaceutical products for HIV of $24 billion in 2017. However, none of the products on the market are able to act on the viral reservoir from infected individuals, and new treatments are needed to achieve a (functional) cure. Clinical development of ABX464: Following two phases I studies conducted on healthy subjects, a first phase IIa study on 66 subjects infected with HIV-1 provided initial evidence of the antiviral activity of ABX464 in humans, while confirming its good tolerability. A second phase IIa study (ABX464-004) was initiated in June 2016 in Spain, Belgium and France, to explore the effect of ABX464 on the viral reservoir (i.e. the immune cells with integrated viral DNA where the virus is “hiding’ during antiretroviral treatment) when used in association with other antivirals. A total of 30 patients were enrolled and treated with ABX464 or placebo for 28 days in addition to boosted Darunavir, which is an established treatment of HIV. The results of this study showed a 25% to 50% reduction in 8 out of 15 evaluable ABX464 treated patients, with no reduction in the placebo group. These results were presented at 9 th IAS Conference on HIV Science in Paris, France on 23-26 July, 2017 and at the 16 th European AIDS Conference (EACS) in Milan, Italy on 25-27 October 2017. In March of 2017, ABIVAX launched a compartmental pharmacokinetics (PK) clinical study (ABX464-005). In this study, HIV infected patients received in cohort 1 ABX464 for 28 days (completed) and for 84 days in cohort 2 (ongoing) in addition to their regular antiretroviral treatment. Also, in cohort 2, rectal biopsies are being collected in addition to blood at different intervals, allowing the quantification of viral reservoir and level of inflammation in intestinal tissue. This study, conducted at the Germans Trias i Pujol University Hospital Badalona (Barcelona, Spain), will provide a better understanding of the reservoir reduction in blood as well as in the gut, which is considered to contain the largest HIV reservoir in the body. Results from the first cohort (28 days of treatment) fully confirmed the results from the previous study: a reduction (up to 50%) of the HIV reservoir in the blood was seen in 8 out of 9 patients (p 1 year) - 10,000 (10,000) of which fixed-term deposits (maturing in < 1 year) 15,000 5,000 10,000 of which available cash flow 2,032 7,987 (5,955) (of which financial debts) (170) (255) 85 Total assets 53,815 60,597 (6,782) Total Equity 48,180 56,718 (8,538) of which equity capital 43,916 54,510 (10,594) of which conditional advances 4,264 2,208 2,056 * Excluding items of the liquidity contract (liquidity and own shares) and deposits & guarantees The assets of the Company at the end of 2017 included goodwill, classified in Intangible Fixed Assets, and resulting from the previous mergers of Wittycell (which contributed the adjuvant platform and the iNK anti-viral agonist adjuvant ABX196) and Splicos (which contributed the antiviral platform and the small molecule ABX464). This goodwill is amounting to €32m since the creation of the company, as of year-end 2014. Due to significant progress in the developments of ABX464 and ABX196, the Company has opted not to proceed to any write-off and the value of those intangible assets remained unchanged in 2017. PERSPECTIVES 2018 In 2018, the Company anticipates achieving the following major milestones: Antiviral platform: Releasing top-line data from the second cohort of the ABX464-005, mid 2018 Filing an IND with the FDA for ABX464 in HIV in H1 of 2018 FSI in phase IIb study for ABX464 in HIV around year end 2018 Releasing top-line data from Phase II POC study in ulcerative colitis in H2 2018 Initiating a phase IIb clinical study of ABX464 in ulcerative colitis around year end 2018 Starting lead optimization for RSV molecule towards the end of H2, 2018 Immune enhancer platform: Filing an IND with the FDA for ABX196 in mid-2018 Initiating a phase I/II POC clinical trial with ABX196 in HCC in H2 2018 FINANCIAL CALENDAR – UPCOMING EVENTS 2018: June 15: Annual General shareholders’ meeting September 19 : 2018 first half year results September 28 : 2018 first half year financial report published on WEBCAST PRESENTATION ABIVAX’s senior management will host a webcast presentation on March 16, 2018 at 3:00 pm CET (Paris time), to discuss FY 2017 results and to provide an update of current activities. Attendees can log on using the following telephone information (Participant, local): Location Phone Austria, Vienna +43 (0)1 928 1466 Belgium, Brussels +32 (0)2 400 6926 France, Paris +33 (0)1 76 77 22 57 Germany, Frankfurt +49 (0)69 2222 2018 Ireland, Dublin +353 (0)1 2465621 Italy, Milan +39 02 3600 9838 Netherlands, Amsterdam +31 (0)20 703 8261 Spain, Madrid +34 91 419 2524 Sweden, Stockholm +46 (0)8 5065 3942 Switzerland, Geneva +41 (0)22 567 5750 United Kingdom, Local +44 (0)330 336 9411 United States, Brooklyn +1 646-828-8193 About ABIVAX ( ) ABIVAX is mobilizing the body’s natural immune machinery to treat patients with viral infections, autoimmune diseases and cancer. A clinical-stage company, ABIVAX leverages its antiviral and immune enhancing platforms to optimize candidates to cure HIV and treat inflammatory bowel diseases and liver cancer. ABIVAX is listed on Euronext compartment B (ISIN: FR0012333284 – Mnémo: ABVX). More information on the company is available at Follow us on Twitter @ABIVAX_ Contacts ABIVAX Finance Didier Blondel didier.blondel@abivax.com +33 1 53 83 08 41 Press Agency ALIZE RP Caroline Carmagnol abivax@alizerp.com +33 1 44 54 36 66 Investors Relations LifeSci Advisors Chris Maggos chris@lifesciadvisors.com +41 79 367 6254 DISCLAIMER This press release contains forward-looking statements, forecasts and estimates with respect to certain of the Company’s programs. Although the Company believes that its forward-looking statements, forecasts and estimates are based on assumptions and assessments of known and unknown risks, uncertainties and other factors that have been deemed reasonable, such forward-looking statements, forecasts and estimates are subject to a number of risks and uncertainties that could cause actual results to differ materially from those anticipated in such forward-looking statements, forecasts and estimates. A description of these risks, contingencies and uncertainties can be found in the documents filed by the Company with the French Autorité des Marchés Financiers pursuant to its legal obligations. Furthermore, these forward-looking statements, forecasts and estimates are only as of the date of this press release. Readers are cautioned not to place undue reliance on these forward-looking statements. ABIVAX disclaims any obligation to update these forward-looking statements, forecasts or estimates to reflect any subsequent changes that the Company becomes aware of, except as required by law. [1] K Chebli et al., The Anti-HIV Candidate ABX464 Dampens Intestinal Inflammation by Triggering Il-22 Production in Activated Macrophages. Nature Scientific Reports 2017, DOI:10.1038/s41598-017-04071-3