ABCA3

Inherited SP-B deficiency is an ultra-rare monogenic cause of fatal respiratory distress syndrome in newborn infants with few, if any, options for long-term survival Highly encouraging preclinical data highlight the possibility of lifelong treatment from a single administration of AVG-002 with preparations for clinical development underway Follows recent grant of Rare Pediatric Disease Designation from FDA 3 December 2024 – AlveoGene (or ‘the Company’, www.alveogene.com), a company focused on transforming rare respiratory disease outcomes using inhaled gene therapy, announces that the US Food & Drug Administration (FDA) has granted Orphan Drug Designation (ODD) to AVG-002, the Company’s novel, inhaled gene therapy for lethal neonatal Surfactant Protein B (SP-B) deficiency. This award follows the recent grant of Rare Pediatric Disease Designation for AVG-002 from FDA in November. Inherited SP-B deficiency is an ultra-rare monogenic cause of fatal respiratory distress syndrome in newborn infants with very limited treatment options. This genetic disorder, affecting approximately 1 in 1 million newborns in the US and Europe, results from mutations in the SP-B gene, which is essential for lung function and survival. Current treatments are mainly supportive, including mechanical ventilation and surfactant replacement, however these interventions only provide temporary relief and once genetic diagnosis of SP-B deficiency is confirmed, treatment is usually withdrawn and patients die. The only definitive treatment, lung transplantation, is often not accessible owing to the scarcity of donor organs for newborns and the risks involved, leaving few if any viable options for long-term survival. David Hipkiss, Executive Chair of AlveoGene, said: “Receiving Orphan Drug Designation from FDA for AVG-002 represents another important milestone for AlveoGene, following the recent grant of Rare Pediatric Disease Designation for the same candidate. Both awards highlight the significant unmet need for novel therapies targeting SP-B deficiency in newborn infants, which is invariably fatal within a few months and for which there are very limited treatment options. AVG-002, a novel gene therapy, has been designed using our InGenuiTy® technology to reach deep into the affected lung tissues to restore lung function and could provide a lifelong treatment from a single administration. We are totally committed to advancing AVG-002 as quickly as possible to provide a transformative, life-saving treatment for patients.” AVG-002 is being developed by AlveoGene using its InGenuiTy® platform, which employs a unique pseudotyped lentiviral vector to deliver a functional SP-B gene directly to the neonatal deep lung alveolar region with high efficiency and efficacy via respiratory instillation. Preclinical data in SP-B gene knock-out murine models demonstrate that a single dose of AVG-002 extends survival substantially longer when compared with reported data of other SP-B deficiency candidates in development, offering the possibility of a lifelong treatment from a single administration. These data are further reinforced by findings that confirm the restoration of normal lung histology and function following AVG-002 treatment in disease-induced lung tissues. Based on these highly encouraging findings, AlveoGene is advancing its preparations for the clinical development of AVG-002 in lethal neonatal SP-B deficiency with the possibility of filing for marketing authorisation by 2028. FDA’s Office of Orphan Drug Products grants Orphan Drug Designation (ODD) to support the development of medicines for rare disorders that affect fewer than 200,000 people in the US. Under the Orphan Drug Act, ODD qualifies a company for incentives, including tax credits, exemptions from certain FDA fees for clinical trials, and the potential for seven years of market exclusivity following drug approval. AlveoGene is a lung-targeted, inhaled gene therapy company aiming to transform the standard of care in respiratory disease and providing therapeutic solutions where few, if any, effective options exist. The Company is advancing a pipeline of novel inhaled gene therapies with enhanced safety, efficacy, durability and improved targeting to lung tissues, based on its unique InGenuiTy® technology. AVG-002 and AVG-003 are potentially first-in-class disease-modifying therapies for newborns with rare lethal Surfactant Protein B (SP-B) and ABCA-3 deficiencies, respectively. AVG-002 is being developed under Rare Pediatric Disease Designation and Orphan Drug Designation with preparations for its clinical development underway. AVG-001 is designed to promote localised production of alpha-1 antitrypsin in the lung to treat patients with Alpha-1 Antitrypsin Deficiency (AATD) lung disease from a single treatment providing an alternative to standard-of-care therapy (weekly IV protein replacement). Preparations for clinical development are underway. AlveoGene was founded in 2023 by Oxford Science Enterprises, Harrington Discovery Institute and Old College Capital in partnership with six leading scientists from the world-renowned UK Respiratory Gene Therapy Consortium (GTC). It is the first company being advanced under the Oxford-Harrington Rare Disease Centre’s Therapeutics Accelerator. The UK Respiratory Gene Therapy Consortium (GTC) comprises world-leading researchers at Imperial College London and the Universities of Oxford and Edinburgh who have worked together for more than 20 years with a focus on translating gene therapy for respiratory diseases. The GTC developed the novel pseudotyped lentiviral vector, which underpins AlveoGene’s InGenuiTy® platform and pipeline, and which is relevant to both Cystic Fibrosis (licensed to and now being developed by Boehringer Ingelheim in the Lenticlair™ clinical trial) and multiple rare and other lung conditions. The content above comes from the network. if any infringement, please contact us to modify.

Inherited SP-B deficiency is an ultra-rare monogenic cause of fatal respiratory distress syndrome in newborn infantsClinical estimates for SP-B deficiency have an incidence of 1 in 1 million live births in the US and EuropeHighly encouraging preclinical data highlight the possibility of lifelong treatment from a single administration of AVG-002Preparations for the clinical development of AVG-002 are underway with the possibility of filing for marketing authorisation by 2028 RPDD provides eligibility for AVG-002 to receive a Priority Review Voucher (PRV) upon future marketing authorisation AlveoGene to present at upcoming Inv€$tival Showcase on 19 November in London, UK Oxford, UK – 15th November 2024 – AlveoGene (or ‘the Company’, www.alveogene.com), a company focused on transforming rare respiratory disease outcomes using inhaled gene therapy, announces that it has been granted a Rare Pediatric Disease Designation (RPDD) by the US Food & Drug Administration (FDA) for AVG-002, its novel inhaled gene therapy for lethal neonatal Surfactant Protein B (SP-B) deficiency. Inherited SP-B deficiency is an ultra-rare monogenic cause of fatal respiratory distress syndrome in newborn infants with very limited treatment options. This genetic disorder, affecting approximately 1 in 1 million newborns in the US and Europe, results from mutations in the SP-B gene, which is essential for lung function and survival. Current treatments are mainly supportive, including mechanical ventilation and surfactant replacement, however these interventions only provide temporary relief and once genetic diagnosis of SP-B deficiency is confirmed, treatment is usually withdrawn and patients die. The only definitive treatment, lung transplantation, is often not accessible owing to the scarcity of donor organs for newborns and the risks involved, leaving few if any viable options for long-term survival. AVG-002 is being developed by AlveoGene using its InGenuiTy® platform, which employs a unique pseudotyped lentiviral vector to deliver a functional SP-B gene directly to the neonatal deep lung alveolar region with high efficiency and efficacy via respiratory instillation. Preclinical data in SP-B gene knock-out murine models demonstrate that a single dose of AVG-002 extends survival substantially longer when compared with reported data of other SP-B deficiency candidates in development, offering the possibility of a lifelong treatment from a single administration. These data are further reinforced by findings that confirm the restoration of normal lung histology and function following AVG-002 treatment in disease-induced lung tissues. Based on these highly encouraging findings, AlveoGene is advancing its preparations for the clinical development of AVG-002 in lethal neonatal SP-B deficiency with the possibility of filing for marketing authorisation by 2028. David Hipkiss, Executive Chair of AlveoGene, said: “This Rare Pediatric Disease Designation (RPDD) for AVG-002 marks a significant step forward in our mission to develop transformative treatments for children with fatal genetic lung diseases. Receiving this RPDD not only underscores the urgent need for innovative therapies in this area but also highlights the potential of our approach in SP-B deficiency in newborn infants, which is designed to target the affected lung tissues directly, restore vital function and provide a viable therapeutic solution where presently there is none. “We similarly expect exciting results with AVG-003, our programme in ABCA-3 deficiency, also a life-threatening rare pediatric genetic respiratory disorder, but with 3-5 times greater incidence than SP-B deficiency. AVG-003 leverages the same novel InGenuiTy® platform technology as AVG-002, and we are optimistic that it might also meet the criteria for an RPDD as we advance its development. “In addition, our excellent preclinical progress with AVG-001 for patients with lung disease as a consequence of Alpha-1 Antitrypsin Deficiency (AATD), continues to give us confidence that it could become a best-in-class treatment that targets the lung directly where its impact on morbidity and mortality is highest and patient numbers are the greatest.” Rare pediatric diseases are defined by the FDA as serious or life-threatening conditions primarily affecting children under 18, with fewer than 200,000 cases in the US. Companies awarded an RPDD receive a rare pediatric disease Priority Review Voucher (PRV) from the FDA when the designated drug is approved for the associated indication in the pediatric population. The voucher allows the recipient company to obtain FDA priority review of either a New Drug Application (NDA) or Biologics License Application (BLA) for a different product and/or indication, reducing the review time and accelerating any granted approval and subsequent market entry by at least four months. The PRV may be used by the original recipient, or it can be sold to another company for the purchaser’s use, with PRVs recently achieving sales prices of $100-$150 million. Executive Chair, David Hipkiss, will present an overview of AlveoGene and its innovative technology and pipeline at the Inv€$tival Showcase on Monday 19 November at 15.00 hrs GMT at the Tobacco Dock in London, UK. ENDS About AlveoGene AlveoGene is a lung-targeted, inhaled gene therapy company aiming to transform the standard of care in respiratory disease and providing therapeutic solutions where few, if any, effective options exist. The Company is advancing a pipeline of novel inhaled gene therapies with enhanced safety, efficacy, durability and improved targeting to lung tissues, based on its unique InGenuiTy® technology. AVG-002 and AVG-003 are potentially first-in-class disease-modifying therapies for newborns with rare lethal Surfactant Protein B (SP-B) and ABCA-3 deficiencies, respectively. AVG-002 is being developed under a Rare Pediatric Disease Designation (RPDD) with preparations for its clinical development underway.AVG-001 is designed to promote localised production of alpha-1 antitrypsin in the lung to treat patients with Alpha-1 Antitrypsin Deficiency (AATD) lung disease from a single treatment providing an alternative to standard-of-care therapy (weekly IV protein replacement). Preparations for clinical development are underway. AlveoGene was founded in 2023 by Oxford Science Enterprises, Harrington Discovery Institute and Old College Capital in partnership with six leading scientists from the world-renowned UK Respiratory Gene Therapy Consortium (GTC). It is the first company being advanced under the Oxford-Harrington Rare Disease Centre’s Therapeutics Accelerator. www.alveogene.com About GTC The UK Respiratory Gene Therapy Consortium (GTC) comprises world-leading researchers at Imperial College London and the Universities of Oxford and Edinburgh who have worked together for more than 20 years with a focus on translating gene therapy for respiratory diseases. The GTC developed the novel pseudotyped lentiviral vector, which underpins AlveoGene’s InGenuiTy® platform and pipeline, and which is relevant to both Cystic Fibrosis (licensed to and now being developed by Boehringer Ingelheim in the Lenticlair™ clinical trial) and multiple rare and other lung conditions. Further details and commentary can be found at www.respiratorygenetherapy.org.uk/ Contacts AlveoGene David Hipkiss, Executive Chair – david.hipkiss@alveogene.com MEDiSTRAVA (for media enquiries) Mark Swallow, Sandi Greenwood, Erica Hollingsworth – alveogene@medistrava.com