PITX3

The U.S. Food and Drug Administration (FDA) has approved Xenpozyme (olipudase alfa-rpcp) for the treatment of non-central nervous system (non-CNS) manifestations of acid sphingomyelinase deficiency (ASMD) in adult and pediatric patients. Xenpozyme is the first therapy indicated specifically for the treatment of ASMD, and is currently the only approved treatment for this disease. Bill Sibold, Executive Vice President, Head, Specialty Care at Sanofi, said: "Sanofi teams have been dedicated to bringing hope to patients living with ASMD and their families. This is a devastating and extremely rare disease that affects both children and adults. The approval of Xenpozyme represents the culmination of bold work done in research and development, and our unwavering commitment to this historically overlooked community." ASMD, historically known as Niemann-Pick disease types A, A/B, and B, is an extremely rare, progressive genetic disease with significant morbidity and mortality. It has been estimated that there are fewer than 120 patients diagnosed with ASMD in the U.S. Approximately two-thirds of patients with ASMD in the U.S. are pediatric. Signs and symptoms of ASMD can present in infancy, childhood, or adulthood, and may include enlarged spleen or liver, difficulty breathing, lung infections, and unusual bruising or bleeding, among other disease manifestations. Until now, management of ASMD included supportive care to address the impact of individual symptoms and careful monitoring to detect potential disease complications. David Guy, Parent to Kaila, age 16, living with ASMD, mentioned: "As young parents, it was initially devastating to me and my wife when our daughter, Kaila, received her diagnosis of ASMD. We faced so many unknowns when we first heard the diagnosis: what does this mean, how will this affect her, and most importantly what hope is there for a treatment option? We were grateful to find hope when we enrolled Kaila in the clinical trials for olipudase alfa." In the U.S., Xenpozyme received Breakthrough Therapy designation, which expedites the development and review of drugs intended to treat serious or life-threatening diseases and conditions. The FDA evaluated Xenpozyme under Priority Review, which is reserved for medicines that represent potentially significant improvements in efficacy or safety in treating serious conditions.. In March 2022, Xenpozyme was approved in Japan under the SAKIGAKE (or "pioneer") designation, marking the first approval for olipudase alfa anywhere in the world. In June 2022, the European Commission (EC) approved Xenpozyme for use in Europe. ASMD represents a spectrum of disease, with two types that may represent opposite ends of a continuum referred to as ASMD type A and ASMD type B. ASMD type A/B is an intermediate form that includes varying degrees of central nervous system (CNS) involvement. ASCEND and ASCEND-Peds clinical trials showed that Xenpozyme improved lung function and reduced spleen and liver volumes in adults and children The approval is based on positive data from the ASCEND and ASCEND-Peds clinical trials, in which Xenpozyme showed clinically relevant improvement in lung function (as measured by diffusing capacity of the lung for carbon monoxide, or DLco) and platelet count, and reduction of spleen and liver volumes, with a demonstrated safety profile. Melissa Wasserstein, MD, Pediatric Genetic Medicine, Albert Einstein College of Medicine and the Childrens Hospital at Montefiore, said: "ASMD is an extremely rare, progressive, and potentially fatal genetic disease that impacts children and adults around the world. Until now, those living with ASMD have had no FDA-approved treatment to combat this devastating condition. Im proud of the work that has been done and look forward to witnessing the impact that this treatment may have on those living with ASMD." The ASCEND trial evaluated the efficacy and safety of Xenpozyme; 31 adult patients with ASMD type A/B or type B were randomized to receive Xenpozyme or placebo for 52 weeks (primary analysis). In the trial, Xenpozyme improved lung function, assessed as the percent change from baseline to Week 52 in predicted diffusing capacity of the lung for carbon monoxide (DLco), and reduced spleen volume, evaluated as percent change from baseline in multiples of normal (MN). Twelve (12) patients treated with Xenpozyme had a mean change in percent predicted DLco from baseline (49.1%) to Week 52 (59.4%). This change represents a 23.9% relative improvement compared to a 3% improvement in DLco from baseline in the 17 patients from the placebo group (48.5%) to Week 52 (49.9%). The difference between the two arms (20.9%) was nominally statistically significant (p=0.0003). Thirteen (13) patients treated with Xenpozyme had a mean reduction in spleen volume by 38.9% from baseline (11.5 MN) to Week 52 (7.2 MN) compared to a mean increase by 0.5% for the 17 patients in the placebo group from baseline (11.2 MN) to Week 52 (11.2 MN). The difference between the two arms (39.4%) was nominally statistically significant (p<0.0001). Twelve (12) patients treated with Xenpozyme had a mean reduction in liver volume by 26.5% from baseline (1.4 MN) to Week 52 (1.0 MN) compared to a mean decrease of 1.8% for the 17 patients in the placebo group from baseline (1.6 MN) to Week 52 (1.6 MN). The difference between the two arms (24.7%) was nominally statistically significant (p<0.0001). Thirteen (13) patients treated with Xenpozyme had a mean improvement in platelet count by 18.3% from baseline (109.3x109/L) to Week 52 (126.4x109/L) compared to increase by 2.7% for the 16 patients in the placebo group from baseline (115.6x109/L) to Week 52 (120.2x109/L). The difference between the two arms (15.6%) was nominally statistically significant (p=0.0280). All ASCEND patients treated with Xenpozyme showed improvement in key endpoints (DLco and spleen and liver volume). Most frequently reported adverse drug reactions in adults (incidence 10%) were headache, cough, diarrhea, hypotension, and ocular hyperemia. The single-arm ASCEND-Peds trial studied 8 pediatric patients younger than 12 years of age with ASMD type A/B or type B who all received Xenpozyme, with a primary objective of evaluating the safety and tolerability of Xenpozyme for 64 weeks. All patients completed the study and continued in an extension trial. The ASCEND-Peds trial also explored efficacy endpoints of progressive lung disease, spleen and liver enlargement, and platelet count. After one year of treatment (52 weeks): Three (3) patients who were able to perform the test at baseline treated with Xenpozyme had a mean relative improvement of 45.9% in percent predicted DLco from baseline (48.5%) to Week 52 (70.9%) (children over the age of five were assessed if they were able to perform the test). Eight (8) patients treated with Xenpozyme had mean reduction in spleen volume by 46.7% from baseline (18.3 MN) to Week 52 (9.5 MN). Eight (8) patients treated with Xenpozyme had a mean reduction in liver volume by 38.1% from baseline (2.5 MN) to Week 52 (1.6 MN). Seven (7) patients treated with Xenpozyme had a mean improvement in platelet count by 37.6% from baseline (136.7x109/L; n=8) to Week 52 (184.5x109/L). Serious adverse reactions of anaphylactic reaction were reported in 2 (25%) Xenpozyme-treated pediatric patients. Treatment-related serious adverse reactions, hypersensitivity reactions including anaphylaxis, and infusion associated reactions occurred within 24 hours of infusion and were observed in a higher percentage of pediatric patients than in adult patients. Most frequently reported adverse drug reactions in pediatric patients (incidence 20%) were pyrexia, cough, diarrhea, rhinitis, abdominal pain, vomiting, headache, urticaria, nausea, rash, arthralgia, pruritus, fatigue, and pharyngitis. A scientific innovation for patients living with ASMD Xenpozyme, a hydrolytic lysosomal sphingomyelin-specific enzyme replacement therapy, is designed to replace deficient or defective acid sphingomyelinase (ASM), an enzyme that allows for the breakdown of the lipid sphingomyelin. In individuals with ASMD, the deficiency in the ASM enzyme leads to sphingomyelin accumulation in various tissues. Xenpozyme is not expected to cross the blood-brain barrier or modulate CNS manifestations of ASMD. Xenpozyme has not been studied in patients with ASMD type A. Xenpozyme is adminstered intravenously every two weeks, and its administration requires a dose escalation phase followed by a maintenance phase. Xenpozyme is expected to be available in the U.S. in the coming weeks. The U.S. list price, or wholesale acquisition cost, of Xenpozyme is $7,142.00 per vial. Actual patient out-of-pocket costs may be lower, as the list price does not reflect insurance coverage, co-pay support for eligible patients, or financial assistance from patient support programs. Sanofi is committed to helping eligible U.S. patients access the support they need and to help reduce barriers throughout their treatment journey. As part of its commitment to treatment access and affordability for innovative therapies, Sanofi provides disease education, financial and co-pay assistance programs, and other support services to eligible patients. For more information, patients can call 1-800-745-4447 and select Option 3, contact Info@CareConnectPSS.com, or visit www.Xenpozyme.com. About Sanofi We are an innovative global healthcare company, driven by one purpose: we chase the miracles of science to improve peoples lives. Our team, across some 100 countries, is dedicated to transforming the practice of medicine by working to turn the impossible into the possible. We provide potentially life-changing treatment options and life-saving vaccine protection to millions of people globally, while putting sustainability and social responsibility at the center of our ambitions. Sanofi is listed on EURONEXT: SAN and NASDAQ: SNY

Chesnot/Getty Images Sanofi announced Wednesday that Xenpozyme (olipudase alfa-rpcp) won FDA approval for adult and pediatric patients with the rare genetic disease acid sphingomyelinase deficiency (ASMD), often referred to as Niemann-Pick disease. In its announcement, the FDA noted that Xenpozyme’s approval is for ASMD symptoms unrelated to the central nervous system. Xenpozyme is the first and only disease-specific drug approved by the FDA for ASMD. Afflicting some 120 patients across the United States, ASMD is an extremely rare disease characterized by an enlarged spleen or liver, difficulties breathing, lung infections, unusual bruises and unexplainable bleeding. ASMD arises when the enzyme that breaks down sphingomyelin is faulty or absent entirely. The lipid then builds up in the liver, spleen, lungs and brain, leading to the tell-tale symptoms. Around two-thirds of all ASMD patients are children, some of whom survive only until two or three years of age. Those who make it into adulthood risk early mortality due to respiratory failure. ASMD is a spectrum disease, with two types representing opposite ends: ASMD type A and type B. The intermediate form ASMD type A/B manifests varying symptoms in the central nervous system. Xenpozyme has not yet been assessed in ASMD type A, nor can it cross the blood-brain barrier. The company has no plans at the moment to study Xenpozyme in other indications. The FDA’s approval was based on promising findings from the Phase II/III ASCEND trial, which enrolled 31 adult patients with ASMD type B or type A/B. Participants were randomly assigned to receive Xenpozyme or a saline placebo through 52 weeks of treatment, after which ASCEND assessed lung function and spleen and liver size. Twelve patients treated with Xenpozyme saw a 23.9% relative improvement in lung function compared to the 3% improvement in placebo comparators. Spleen and liver volume likewise dropped by 38.9% and 26.5%, respectively, after 52 weeks of Xenpozyme. Those in the placebo arm saw spleen volume increase by 0.5% and liver volume decrease by 1.8%. A Long Journey to Approval Xenpozyme is a hydrolytic lysosomal sphingomyelin-specific enzyme replacement therapy. It treats ASMD by replacing the missing or defective acid sphingomyelinase enzyme in patients, restoring the body’s ability to break down the complex lipid. Sanofi first got a hold of Xenpozyme in 2011, when it acquired Genzyme in a $20 billion deal. Two years later, in December 2013, Sanofi initiated ASCEND but could only commence treatment and assessments in 2015. ASCEND reached initial completion in March last year, and data started rolling in April. "As is common in rare-disease research, the clinical development program for Xenpozyme had slow study enrollment due to a number of factors, including the rarity of ASMD, the fact that many patients remain undiagnosed, complexity of the molecule and its development, and difficulties common to most clinical trials, such as strict inclusion and exclusion criteria and the burdens of study participation," a Sanofi spokesperson told BioSpace. Another ongoing study of Xenpozyme began at the same time and is expected to end in 2024. This open-label single-group study is a long-term assessment of Xenpozyme’s efficacy and safety, as well as its pharmacodynamic and pharmacokinetic pro Along the way, Xenpozyme was awarded the FDA’s fast track, breakthrough therapy, priority review and orphan drug designations. Sanofi also won a rare pediatric disease priority review voucher from the regulator as an incentive to encourage the company to develop drugs and biologics for rare diseases in children. Xenpozyme’s first approval came in March when it was given the green light by Japan’s Ministry of Health, Labor and Welfare under the country’s SAKIGAKE program for pioneering medicines. The European Commission followed suit three months later.

XenpozymeTM (olipudase alfa-rpcp) approved by FDA as first disease-specific treatment forASMD (non-CNS manifestations) Paris, August 31, 2022. The U.S. Food and Drug Administration (FDA) has approved XenpozymeTM (olipudase alfa-rpcp) for the treatment of non-central nervous system (non-CNS) manifestations of acid sphingomyelinase deficiency (ASMD) in adult and pediatric patients. Xenpozyme is the first therapy indicated specifically for the treatment of ASMD, and is currently the only approved treatment for this disease. Bill Sibold Executive Vice President, Head, Specialty Care at Sanofi “Sanofi teams have been dedicated to bringing hope to patients living with ASMD and their families. This is a devastating and extremely rare disease that affects both children and adults. The approval of Xenpozyme represents the culmination of bold work done in research and development, and our unwavering commitment to this historically overlooked community.” ASMD, historically known as Niemann-Pick disease types A, A/B, and B, is an extremely rare, progressive genetic disease with significant morbidity and mortality. It has been estimated that there are fewer than 120 patients diagnosed with ASMD in the U.S. Approximately two-thirds of patients with ASMD in the U.S. are pediatric. Signs and symptoms of ASMD can present in infancy, childhood, or adulthood, and may include enlarged spleen or liver, difficulty breathing, lung infections, and unusual bruising or bleeding, among other disease manifestations. Until now, management of ASMD included supportive care to address the impact of individual symptoms and careful monitoring to detect potential disease complications. David Guy Parent to Kaila, age 16, living with ASMD “As young parents, it was initially devastating to me and my wife when our daughter, Kaila, received her diagnosis of ASMD. We faced so many unknowns when we first heard the diagnosis: what does this mean, how will this affect her, and most importantly what hope is there for a treatment option? We were grateful to find hope when we enrolled Kaila in the clinical trials for olipudase alfa.” In the U.S., Xenpozyme received Breakthrough Therapy designation, which expedites the development and review of drugs intended to treat serious or life-threatening diseases and conditions. The FDA evaluated Xenpozyme under Priority Review, which is reserved for medicines that represent potentially significant improvements in efficacy or safety in treating serious conditions.. In March 2022, Xenpozyme was approved in Japan under the SAKIGAKE (or “pioneer”) designation, marking the first approval for olipudase alfa anywhere in the world. In June 2022, the European Commission (EC) approved Xenpozyme for use in Europe. ASMD represents a spectrum of disease, with two types that may represent opposite ends of a continuum referred to as ASMD type A and ASMD type B. ASMD type A/B is an intermediate form that includes varying degrees of central nervous system (CNS) involvement. ASCEND and ASCEND-Peds clinical trials showed that Xenpozyme improved lung function and reduced spleen and liver volumes in adults and children The approval is based on positive data from the ASCEND and ASCEND-Peds clinical trials, in which Xenpozyme showed clinically relevant improvement in lung function (as measured by diffusing capacity of the lung for carbon monoxide, or DLco) and platelet count, and reduction of spleen and liver volumes, with a demonstrated safety profile. Melissa Wasserstein MD, Pediatric Genetic Medicine, Albert Einstein College of Medicine and the Children’s Hospital at Montefiore “ASMD is anextremely rare, progressive, and potentially fatal genetic disease that impacts children and adults around the world. Until now, those living with ASMD have had no FDA-approved treatment to combat this devastating condition. I’m proud of the work that has been done and look forward to witnessing the impact that this treatment may have on those living with ASMD.” The ASCEND trial evaluated the efficacy and safety of Xenpozyme; 31 adult patients with ASMD type A/B or type B were randomized to receive Xenpozyme or placebo for 52 weeks (primary analysis). In the trial, Xenpozyme improved lung function, assessed as the percent change from baseline to Week 52 in predicted diffusing capacity of the lung for carbon monoxide (DLco), and reduced spleen volume, evaluated as percent change from baseline in multiples of normal (MN). Twelve (12) patients treated with Xenpozyme had a mean change in percent predicted DLco from baseline (49.1%) to Week 52 (59.4%). This change represents a 23.9% relative improvement compared to a 3% improvement in DLco from baseline in the 17 patients from the placebo group (48.5%) to Week 52 (49.9%). The difference between the two arms (20.9%) was nominally statistically significant (p=0.0003). Thirteen (13) patients treated with Xenpozyme had a mean reduction in spleen volume by 38.9% from baseline (11.5 MN) to Week 52 (7.2 MN) compared to a mean increase by 0.5% for the 17 patients in the placebo group from baseline (11.2 MN) to Week 52 (11.2 MN). The difference between the two arms (39.4%) was nominally statistically significant (p<0.0001). Twelve (12) patients treated with Xenpozyme had a mean reduction in liver volume by 26.5% from baseline (1.4 MN) to Week 52 (1.0 MN) compared to a mean decrease of 1.8% for the 17 patients in the placebo group from baseline (1.6 MN) to Week 52 (1.6 MN). The difference between the two arms (24.7%) was nominally statistically significant (p<0.0001). Thirteen (13) patients treated with Xenpozyme had a mean improvement in platelet count by 18.3% from baseline (109.3x109/L) to Week 52 (126.4x109/L) compared to increase by 2.7% for the 16 patients in the placebo group from baseline (115.6x109/L) to Week 52 (120.2x109/L). The difference between the two arms (15.6%) was nominally statistically significant (p=0.0280). All ASCEND patients treated with Xenpozyme showed improvement in key endpoints (DLco and spleen and liver volume). Most frequently reported adverse drug reactions in adults (incidence ≥10%) were headache, cough, diarrhea, hypotension, and ocular hyperemia. The single-arm ASCEND-Peds trial studied 8 pediatric patients younger than 12 years of age with ASMD type A/B or type B who all received Xenpozyme, with a primary objective of evaluating the safety and tolerability of Xenpozyme for 64 weeks. All patients completed the study and continued in an extension trial. The ASCEND-Peds trial also explored efficacy endpoints of progressive lung disease, spleen and liver enlargement, and platelet count. After one year of treatment (52 weeks): Three (3) patients who were able to perform the test at baseline treated with Xenpozyme had a mean relative improvement of 45.9% in percent predicted DLco from baseline (48.5%) to Week 52 (70.9%) (children over the age of five were assessed if they were able to perform the test). Eight (8) patients treated with Xenpozyme had mean reduction in spleen volume by 46.7% from baseline (18.3 MN) to Week 52 (9.5 MN). Eight (8) patients treated with Xenpozyme had a mean reduction in liver volume by 38.1% from baseline (2.5 MN) to Week 52 (1.6 MN). Seven (7) patients treated with Xenpozyme had a mean improvement in platelet count by 37.6% from baseline (136.7x109/L; n=8) to Week 52 (184.5x109/L). Serious adverse reactions of anaphylactic reaction were reported in 2 (25%) Xenpozyme-treated pediatric patients. Treatment-related serious adverse reactions, hypersensitivity reactions including anaphylaxis, and infusion associated reactions occurred within 24 hours of infusion and were observed in a higher percentage of pediatric patients than in adult patients. Most frequently reported adverse drug reactions in pediatric patients (incidence ≥20%) were pyrexia, cough, diarrhea, rhinitis, abdominal pain, vomiting, headache, urticaria, nausea, rash, arthralgia, pruritus, fatigue, and pharyngitis. A scientific innovation for patients living with ASMD Xenpozyme, a hydrolytic lysosomal sphingomyelin-specific enzyme replacement therapy, is designed to replace deficient or defective acid sphingomyelinase (ASM), an enzyme that allows for the breakdown of the lipid sphingomyelin. In individuals with ASMD, the deficiency in the ASM enzyme leads to sphingomyelin accumulation in various tissues. Xenpozyme is not expected to cross the blood-brain barrier or modulate CNS manifestations of ASMD. Xenpozyme has not been studied in patients with ASMD type A. Xenpozyme is adminstered intravenously every two weeks, and its administration requires a dose escalation phase followed by a maintenance phase. Xenpozyme is expected to be available in the U.S. in the coming weeks. The U.S. list price, or wholesale acquisition cost, of Xenpozyme is $7,142.00 per vial. Actual patient out-of-pocket costs may be lower, as the list price does not reflect insurance coverage, co-pay support for eligible patients, or financial assistance from patient support programs. Sanofi is committed to helping eligible U.S. patients access the support they need and to help reduce barriers throughout their treatment journey. As part of its commitment to treatment access and affordability for innovative therapies, Sanofi provides disease education, financial and co-pay assistance programs, and other support services to eligible patients. For more information, patients can call 1-800-745-4447 and select Option 3, contact Info@CareConnectPSS.com, or visit About Sanofi We are an innovative global healthcare company, driven by one purpose: we chase the miracles of science to improve people’s lives. Our team, across some 100 countries, is dedicated to transforming the practice of medicine by working to turn the impossible into the possible. We provide potentially life-changing treatment options and life-saving vaccine protection to millions of people globally, while putting sustainability and social responsibility at the center of our ambitions. Sanofi is listed on EURONEXT: SAN and NASDAQ: SNY Media Relations Sandrine Guendoul | + 33 6 25 09 14 25 | sandrine.guendoul@sanofi.com Sally Bain | + 1 617 834 6026 | sally.bain@sanofi.com Kate Conway | + 1 508 364 4931| kate.conway@sanofi.com Investor Relations Eva Schaefer-Jansen | + 33 7 86 80 56 39 | eva.schaefer-jansen@sanofi.com Arnaud Delépine | + 33 6 73 69 36 93 | arnaud.delepine@sanofi.com Corentine Driancourt | + 33 6 40 56 92 21 | corentine.driancourt@sanofi.com Felix Lauscher | + 1 908 612 7239 | felix.lauscher@sanofi.com Priya Nanduri | + 1 617 764 6418 | priya.nanduri@sanofi.com Nathalie Pham | + 33 7 85 93 30 17 | nathalie.pham@sanofi.com Sanofi Forward-Looking Statements This press release contains forward-looking statements as defined in the Private Securities Litigation Reform Act of 1995, as amended. Forward-looking statements are statements that are not historical facts. These statements include projections and estimates regarding the marketing and other potential of the product, or regarding potential future revenues from the product. Forward-looking statements are generally identified by the words "expects", "anticipates", "believes", "intends", "estimates", "plans" and similar expressions. Although Sanofi's management believes that the expectations reflected in such forward-looking statements are reasonable, investors are cautioned that forward-looking information and statements are subject to various risks and uncertainties, many of which are difficult to predict and generally beyond the control of Sanofi, that could cause actualresults and developments to differ materially from those expressed in, or implied or projected by, the forward-looking information and statements. 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