Soft tissue inflammation

SAN FRANCISCO and SUZHOU, China, May 20, 2024 /PRNewswire/ -- Innovent Biologics, Inc. ("Innovent") (HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures and commercializes high-quality medicines for the treatment of cancer, metabolic, autoimmune, ophthalmology and other major diseases, today announced that the New Drug Application (NDA) for IBI311, a recombinant anti-insulin-like growth factor 1 receptor (IGF-1R) antibody, has been accepted and granted priority review designation by the Center for Drug Evaluation (CDE) of the China National Drug Administration (NMPA) for the treatment of Thyroid Eye Disease (TED). IBI311 is the first anti-IGF-1R antibody with NDA submitted in China. As a biological drug with a novel mechanism of action, IBI311 will potentially resolve an over 60-years shortage of innovative TED drugs in China by offering an effective, safe and accessible treatment option for Chinese TED patients. This NDA was accepted based on the positive results of a Phase 3 registration clinical study RESTORE-1 (CTR20223393) in subjects with TED in China. The primary endpoint of the study was successfully met in February 2024. Significant improvements in proptosis, disease activity, and quality of life were observed in the IBI311 group compared to placebo. The overall safety profile of IBI311 was favorable, and no new safety signals were identified. Detailed results of the RESTORE-1 study will be presented at medical conferences or journals in 2024. TED is an autoimmune disease that causes progressive inflammation and damage to tissues around the eyes. The annual incidence of TED is estimated to be 16/100,000 in women and 2.9/100,000 in men [1], with the estimated prevalence of 0.1-0.3%[2].The use of IGF-1R-targeted antibody has been recommended in multiple clinical treatment guidelines worldwide[3, 4, 5]; particularly, IGF-1R-targeted antibody is recommended as first-line therapy for patients with clinically significant proptosis. In China, there exists an urgent need for effective, safe and accessible treatment options. Professor Xianqun Fan, an academician of the Chinese Academy of Engineering and the leading principal investigator of the study, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, stated, "TED is one of the most common orbital diseases in adults, with proptosis as the most apparent clinical manifestation. The course of TED is protracted, which seriously impairs patients' visual function and appearance, and usually brings a heavy psychological burden to patients. In China, physicians are hampered with limited choice of treatment. IBI311 has shown encouraging efficacy with respect to proptosis and orbital soft tissue inflammation with good safety in clinical studies. As the principal investigator of the RESTORE-1 study, I am proud of the NDA submission based on IBI311's promising efficacy and safety demonstrated in the pivotal study and would like to thank the effort of all investigators from participating sites. We look forward to the approval of IBI311, which will be a great advance in the management of TED and benefit more Chinese patients." Dr. Lei Qian, Vice President of Clinical Development of Innovent, stated, "We are honored to receive the regulatory acceptance of NDA for IBI311 with the support and dedication of participants, investigators and regulatory authorities. IBI311 has demonstrated favorable safety and comprehensive efficacy benefits in the RESTORE-1 study, including relief of proptosis, control of disease activity, and improvement in quality of life. We will actively communicate with the regulatory authorities during the NDA review and hope to provide an effective, safe and more accessible treatment option for Chinese TED patients as soon as possible. Innovent is strategically establishing its innovative commercial and late-stage portfolio in the fields of ophthalmology, autoimmunity, cardiovascular and metabolic (CVM) , aiming to help more people pursue a healthy life." About Thyroid Eye Disease (TED) TED is an autoimmune disease involving ocular tissues and is usually associated with Graves' disease (GD) and is the most common orbit-related disease in adults. TED occurs in approximately 25 to 50% of GD patients and can also be seen in other thyroid diseases, even in euthyroidism[6]. The annual incidence of TED is estimated to be 16/100,000 in women and 2.9/100,000 in men[1]，and the estimated prevalence of clinically relevant TED ranges from 0.1% to 0.3%[2]. According to disease severity, it can be divided into mild, moderate and severe. Although TED appears to affect women more often, severe cases occur more frequently in men. Patients aged 30 to 50 years are most commonly affected, and severe cases occur more frequently in patients over 50 years[7]. At present, the pathogenesis of TED is not fully understood, but several studies have shown that orbital fibrous present in muscle fibers, orbital fibrous connective tissue space are key factors leading to orbital soft tissue enlargement in TED[8]. The natural history of TED is divided into active and inactive phases[9]. The most common symptoms are dry eye, ocular gritty, photophobia, lacrimation, diplopia, and pressure behind the eye, while typical signs include upper eyelid retraction, eyelid edema, periorbital and conjunctival edema, and proptosis. TED is usually mild to moderate, and about 3–5% of patients with TED are severe, manifesting as severe pain, vision-threatening corneal ulcers, or compressive optic neuropathy[10]. In addition to potentially affecting vision, TED can have an extremely severe impact on the patient's appearance and social functioning and quality of life. Currently, the first-line treatment option for moderately severe active TED is intravenous glucocorticoid therapy, which suffers from unsatisfactory improvement of proptosis and systemic side effects, and second-line treatment includes other immunomodulators, which also have risks related to unclear improvement of proptosis and treatment. Teprotumumab, Tocilizumab and Rituximab are recommended by the Chinese Clinical Diagnosis and Treatment Guidelines for Thyroid Eye Disease (2022)[3], the European Group on Graves' orbitopathy (EUGOGO)[4] and the consensus on thyroid eye disease of the American Thyroid Society and the European Thyroid Society[5] as the second-line treatment options for moderate to severe active TED. Teprotumumab targeting IGF-1R is recommended as first-line therapy for patients with clinically significant proptosis. About IBI311 IBI311 is a recombinant anti-IGF-1R antibody developed by Innovent for the treatment of TED. IGF-1R is a transmembrane tyrosine kinase receptor that plays a role in the development, metabolism, and immune regulation, and is overexpressed in OFs, B, and T cells of TED patients[11]. IBI311 can bind IGF-1R, block IGF-1R signaling pathway activation mediated by IGF-1 and other related ligands or agonistic antibodies, reduce the expression of downstream inflammatory factors, thereby inhibiting the synthesis of hyaluronic acid and other glycosaminoglycan caused by OFs activation, as well as related inflammatory reactions including tissue congestion and edema; inhibit adipocyte cellularization of OFs, thereby reducing the disease activity of patients with TED and improving proptosis, diplopia, ocular congestion and edema among other symptoms and signs. In May 2024, the NDA for IBI311 was accepted by the NMPA for the treatment of TED. About Innovent Innovent is a leading biopharmaceutical company founded in 2011 with the mission to empower patients worldwide with affordable, high-quality biopharmaceuticals. The company discovers, develops, manufactures and commercializes innovative medicines that treat some of the most intractable illnesses. Its pioneering therapies to treat cancer, cardiovascular and metabolic, autoimmune and eye diseases. Innovent has 10 products in the market, 4 new drug applications under the NMPA review, 4 assets in Phase III or pivotal clinical trials and 18 more molecules in early clinical stage. Innovent partners with over 30 global healthcare leaders, including Eli Lilly, Roche, Sanofi, Adimab, Incyte and MD Anderson Cancer Center. Guided by the motto, "Start with Integrity, Succeed through Action," Innovent maintains the highest standard of industry practices and works collaboratively to advance the biopharmaceutical industry so that first-rate pharmaceutical drugs can become widely accessible. For more information, visit , or follow Innovent on Facebook and LinkedIn. Statement: Innovent does not recommend the use of any unapproved drug (s)/indication (s). Forward-looking statement This news release may contain certain forward-looking statements that are, by their nature, subject to significant risks and uncertainties. The words "anticipate", "believe", "estimate", "expect", "intend" and similar expressions, as they relate to Innovent Biologics ("Innovent"), are intended to identify certain of such forward-looking statements. The Company does not intend to update these forward-looking statements regularly. These forward-looking statements are based on the existing beliefs, assumptions, expectations, estimates, projections and understandings of the management of the Company with respect to future events at the time these statements are made. These statements are not a guarantee of future developments and are subject to risks, uncertainties and other factors, some of which are beyond the Company's control and are difficult to predict. Consequently, actual results may differ materially from information contained in the forward-looking statements as a result of future changes or developments in our business, the Company's competitive environment and political, economic, legal and social conditions. The Company, the Directors and the employees of the Company assume (a) no obligation to correct or update the forward-looking statements contained in this site; and (b) no liability in the event that any of the forward-looking statements does not materialize or is otherwise inaccurate. References 1. Li Z, Cestari D M, Fortin E. Thyroid eye disease: what is new to know? Curr Opin Ophthalmol. 2018; 29 (6): 528-534. 2. Bartley G. The epidemiological characteristics and clinical course of ophthalmology associated with autoimmune thyroid disease in Olmsted Country, Minnesota. Trans Am Ophthalmol Soc 1994; 92: 477-588. 3. Hiromatsu Y, Eguchi H, Tani J, Kasaoka M, Teshima Y. Graves' ophthalmopathy: epidemiology and natural history. Intern Med. 2014; 53 (5): 353-60. 4. Edsel I. Thyroid Associated Orbitopathy. Retrieved June 7, 2011, from Medscape Reference: # a1 5. Ali F, Chorsiya A, Anjum V, Ali A. Teprotumumab (TEPEZZA): From the Discovery and Development of Medicines to USFDA Approvals for Active Thyroid Eye Disease (TED) Treatment. Int Ophthalmol. 2021; 41 (4): 1549-1561. 6. Dolman P J. Evaluating Graves' orbitopathy. Best Pract Res Clin Endocrinol Metab. 2012; 26 (3): 229-248. 7. Bahn R S. Graves' ophthalmopathy. N Engl J Med. 2010; 362 (8): 726-738. 8. Bartalena L, Kahaly GJ, Baldeschi L, et al. The 2021 European Group on Graves' Orbitopathy (EUGOGO) clinical practice guidelines for the medical management of Graves' Orbitopathy. Eur J Endocrinol. 2021; 185 (4): G43-G67. 9. Group of Oculoplastic and Orbital Diseases, Chinese Ophthalmology Branch, Chinese Medical Association; Group of Thyroid Diseases, Chinese Endocrinology Branch, Chinese Medical Association. Chinese Guidelines for the Diagnosis and Treatment of Thyroid Associated Ophthalmopathy (2022). Chinese Journal of Ophthalmology. 2022; 58 (9). 10. Burch HB, et al. Management of Thyroid Eye Disease: a Consensus Statement by the American Thyroid Association and the European Thyroid Association. Eur Thyroid J. 2022; 11 (6): e220189. 11. Douglas RS, Naik V, Hwang CJ, et al. B cells from patients with Graves' disease erase express the IGF-1 receptor: implications for disease pathogenesis. J Immunol 2008; 181: 5768-5774. SOURCE Innovent Biologics

MoonLake Immunotherapeutics starts Phase 3 VELA program of the Nanobody® sonelokimab in patients with moderate-to-severe hidradenitis suppurativa VELA is the first Phase 3 program in hidradenitis suppurativa to use the higher clinical response level of HiSCR75 as the primary endpoint The topline primary endpoint readout at week 16, together with data on other endpoints, is expected as of mid-2025 Program will evaluate sonelokimab for a total of 52 weeks, across VELA-1 and VELA-2, at sites in the United States and Europe, using a design informed by the landmark Phase 2 MIRA trial Zug, Switzerland, May 16, 2024 – MoonLake Immunotherapeutics (MoonLake; Nasdaq: MLTX), a clinical-stage biotechnology company focused on creating next-level therapies for inflammatory diseases, today announced that the first patients have been screened at a U.S. trial site in its global Phase 3 clinical program, VELA, evaluating sonelokimab, an investigational Nanobody® designed to treat inflammatory disease, in patients with moderate-to-severe hidradenitis suppurativa (HS). HS is a severely debilitating chronic skin condition, affecting up to 4.1% of the global population. Over time, uncontrolled and inadequately treated inflammation can result in irreversible tissue destruction and scarring. Sonelokimab is designed to directly target sites of inflammation by inhibiting the IL-17A/A, IL-17A/F, and IL-17F/F dimers and to penetrate difficult-to-reach inflamed tissues. Following the positive results from the landmark Phase 2 MIRA trial, the Phase 3 VELA program is expected to enroll 800 patients across VELA-1 and VELA-2. Both trials are identical in design comparing a single 120mg dose of sonelokimab to placebo with the higher measure of clinical response, Hidradenitis Suppurativa Clinical Response (HiSCR) 75, as the primary endpoint reading out at week 16. From week 16, all patients will receive the 120mg dose of sonelokimab through to 52 weeks, followed by an open-label extension for up to two years. The Phase 3 program will use a protocol design consistent with the Phase 2 MIRA trial, which identified the optimal dose of sonelokimab for HS. The topline primary endpoint readout (week 16) from the VELA program is expected as of mid-2025. Kristian Reich, Founder and Chief Scientific Officer at MoonLake commented: “With real-world data indicating that at least two million Americans have been diagnosed with and treated for HS, the launch of our Phase 3 VELA program with our Nanobody® sonelokimab, using the higher clinical measure of HiSCR75 as the primary endpoint and a straightforward, proven study design is a landmark moment in our efforts to develop novel treatment options for patients suffering with this under-diagnosed and under-treated condition. We are making significant progress in establishing clinical trial sites to enroll 800 patients, and we eagerly anticipate reporting the week 16 primary endpoint readout around mid-2025.” Hadar Lev-Tov, MD, MAS, Associate Professor, Director Wound Healing Fellowship, President Hidradenitis Suppurativa Foundation,Dr. Phillip Frost Department of Dermatology and Cutaneous Surgery, University of Miami, Miller School of Medicine, added:“HS is a chronic inflammatory skin condition with a range of debilitating symptoms including pain, malodorous drainage, low mood and depression. With only two FDA approved biologics, there is still an urgent need for new treatment options that treat all patient types and lesions, with the opportunity for inflammatory remission. The unique characteristics and mode of action of MoonLake’s Nanobody®, sonelokimab to effectively inhibit IL-17F in addition to IL-17A in deep tissue inflammation has to date shown promising outcomes, highlighting the importance of this Phase 3 program, and placing HS at the forefront of dermatological innovation.” Seth B Forman, MD, Principal Investigator at CenExel-FCR added:“It is with great enthusiasm that I am participating as an investigator in the Phase 3 VELA program investigating the Nanobody sonelokimab for HS, signifying a substantial advancement in addressing the critical unmet need for more treatment options for individuals living with HS. As a physician, I witness first-hand the immense demand for novel treatment options for people living with HS, particularly those that can achieve elevated response thresholds (e.g., HiSCR75 and beyond). The findings from the Phase 2 MIRA trial offer valuable insights into what may be possible as we work with our patients to establish more ambitious treatment goals and alleviate the disease burden of this debilitating condition”. The initiation of this Phase 3 program follows the announcement in February 2024 of the successful outcome of MoonLake’s end-of-Phase 2 interactions with the U.S. Food and Drug Administration (FDA), as well as positive feedback from its interactions with the European Medicines Agency (EMA), with both regulatory bodies unanimously supporting MoonLake’s proposed approach for advancing its Phase 3 program in HS. Sonelokimab is not yet approved for use in any indication. – Ends – About the VELA program The Phase 3 VELA program is expected to enroll 800 patients across VELA-1 and VELA-2. Both global, randomized, double-blind, placebo-controlled trials are identical in design evaluating the efficacy and safety of the Nanobody® sonelokimab, administered subcutaneously, in adult patients with active moderate-to-severe hidradenitis suppurativa. Similar to the design of the landmark Phase 2 MIRA trial, the primary endpoint is the percentage of participants achieving Hidradenitis Suppurativa Clinical Response 75 (HiSCR75), defined as a ≥75% reduction in total abscess and inflammatory nodule (AN) count with no increase in abscess or draining tunnel count relative to baseline. The trials will also evaluate a number of secondary endpoints, including the proportion of patients achieving HiSCR50, the change from baseline in International Hidradenitis Suppurativa Severity Score System (IHS4), the proportion of patients achieving a Dermatology Life Quality Index (DLQI) total reduction of ≥4, the proportion of patients achieving at least 50% reduction from baseline in Numerical Rating Scale (NRS50) in the Patient’s Global Assessment of Skin Pain (PGA Skin Pain) and complete resolution of Draining Tunnels (DT100). Further details are available under NCT06411379 and NCT06411899 at ClinicalTrials.gov. About Sonelokimab Sonelokimab (M1095) is an investigational ~40 kDa humanized Nanobody® consisting of three VHH domains covalently linked by flexible glycine-serine spacers. With two domains, sonelokimab selectively binds with high affinity to IL-17A and IL-17F, thereby inhibiting the IL-17A/A, IL-17A/F, and IL-17F/F dimers. A third central domain binds to human albumin, facilitating further enrichment of sonelokimab at sites of inflammatory edema. Sonelokimab is being assessed in two lead indications, HS and psoriatic arthritis (PSA), and the Company is pursuing other indications in dermatology and rheumatology. For HS, sonelokimab is being assessed in the Phase 3 trials, VELA-1 and VELA-2, following the successful outcome of MoonLake’s end-of-Phase 2 interactions with the FDA and as well as positive feedback from its interactions with the EMA announced in February 2024. In June 2023, topline results of the MIRA trial (NCT05322473) at 12 weeks showed that the trial met its primary endpoint, the Hidradenitis Suppurativa Clinical Response (HiSCR)75, which is a higher measure of clinical response versus the HiSCR50 measure used in other clinical trials, setting a landmark milestone. In October 2023, the full dataset from the MIRA trial at 24 weeks showed that maintenance treatment with sonelokimab led to further improvements in HiSCR75 response rates and other high threshold clinical and patient relevant outcomes. The safety pro sonelokimab in the MIRA trial was consistent with previous trials with no new safety signals detected. For PsA, Phase 3 initiation is anticipated in Q4 2024 following the announcement in March 2024 of the full dataset from the global Phase 2 ARGO trial (M1095-PSA-201) evaluating the efficacy and safety of the Nanobody® sonelokimab over 24 weeks in patients with active PsA. Significant improvements were observed across all key outcomes, including approximately 60% of patients treated with sonelokimab achieving an American College of Rheumatology (ACR) 50 response and Minimal Disease Activity (MDA) at week 24. This followed the positive top-line results in November 2023, where the trial met its primary endpoint with a statistically significant greater proportion of patients treated with either sonelokimab 60mg or 120mg (with induction) achieving ACR50 response compared to those on placebo at week 12. All key secondary endpoints in the trial were met for the 60mg and 120mg doses with induction. The safety pro sonelokimab in the ARGO trial was consistent with previous trials with no new safety signals detected. A Phase 2 trial is expected to be initiated in 2024 for palmo-plantar pustulosis (PPP), a debilitating inflammatory skin condition affecting a significant number of patients. In addition, a Phase 3 trial is expected to initiate in juvenile HS, a condition that typically manifests at this early stage of a patient’s life, and the period in which irreversible damage and inflammatory remission is most critical. Sonelokimab will also be assessed in seronegative spondyloarthritis with Phase 2 trials in radiographic and non-radiographic axial spondyloarthritis (axSpA) and PsA expected to start in 2024. The trials are set to incorporate innovative designs that enhance traditional clinical outcomes with contemporary tissue and cellular imaging techniques. Sonelokimab has also been assessed in a randomized, placebo-controlled Phase 2b trial (NCT03384745) in 313 patients with moderate-to-severe plaque-type psoriasis. High threshold clinical responses (Investigator’s Global Assessment Score 0 or 1, and Psoriasis Area and Severity Index 90/100) were observed in patients with moderate-to-severe plaque-type psoriasis. Sonelokimab was generally well tolerated, with a safety pro to the active control, secukinumab (Papp KA, et al. Lancet. 2021; 397:1564-1575). In an earlier Phase 1 trial in patients with moderate-to-severe plaque-type psoriasis, sonelokimab has been shown to decrease (to normal skin levels) the cutaneous gene expression of pro-inflammatory cytokines and chemokines (Svecova D. J Am Acad Dermatol. 2019;81:196–203). About Nanobodies® Nanobodies® represent a new generation of antibody-derived targeted therapies. They consist of one or more domains based on the small antigen-binding variable regions of heavy-chain-only antibodies (VHH). Nanobodies® have a number of potential advantages over traditional antibodies, including their small size, enhanced tissue penetration, resistance to temperature changes, ease of manufacturing, and their ability to be designed into multivalent therapeutic molecules with bespoke target combinations. The terms Nanobody® and Nanobodies® are trademarks of Ablynx, a Sanofi company. About Hidradenitis Suppurativa Hidradenitis suppurativa is a severely debilitating chronic skin condition resulting in irreversible tissue destruction. HS manifests as painful inflammatory skin lesions, typically around the armpits, groin, and buttocks. Over time, uncontrolled and inadequately treated inflammation can result in irreversible tissue destruction and scarring. The disease affects 0.05–4.1% of the global population, with three times more females affected than males. Real-world data in the US indicates that at least 2 million unique patients have been diagnosed with and treated for HS between 2016 and 2023 alone, highlighting a significant unmet need and impact on healthcare systems, and a market opportunity exceeding $10bn by 2035. Onset typically occurs in early adulthood and HS has a profound negative impact on quality of life, with a higher morbidity than other dermatologic conditions. There is increasing scientific evidence to support IL-17A- and IL-17F-mediated inflammation as a key driver of the pathogenesis of HS, with other identified risk factors including genetics, cigarette smoking, and obesity. About MoonLake Immunotherapeutics MoonLake Immunotherapeutics is a clinical-stage biopharmaceutical company unlocking the potential of sonelokimab, a novel investigational Nanobody® for the treatment of inflammatory disease, to revolutionize outcomes for patients. Sonelokimab inhibits IL-17A and IL-17F by inhibiting the IL-17A/A, IL-17A/F, and IL-17F/F dimers that drive inflammation. The company’s focus is on inflammatory diseases with a major unmet need, including hidradenitis suppurativa and psoriatic arthritis – conditions affecting millions of people worldwide with a large need for improved treatment options. MoonLake was founded in 2021 and is headquartered in Zug, Switzerland. Further information is available at . Cautionary Statement Regarding Forward Looking Statements This press release contains certain “forward-looking statements” within the meaning of the U.S. Private Securities Litigation Reform Act of 1995. Forward-looking statements include, but are not limited to, statements regarding MoonLake’s expectations, hopes, beliefs, intentions or strategies regarding the future including, without limitation, statements regarding: plans for and timing of clinical trials, including the topline primary endpoint readout for the Phase 3 VELA program, the trial design and patient enrollment across the VELA-1 and VELA-2 trials, the initiation of the Phase 3 program in PsA, commencement of clinical trials of sonelokimab in PPP, juvenile HS and seronegative spondyloarthritis, the efficacy and safety of sonelokimab for the treatment of HS and PsA, including in comparison to existing standards or care or other competing therapies, clinical trials and research and development programs and the anticipated timing of the results from those studies and trials. In addition, any statements that refer to projections, forecasts, or other characterizations of future events or circumstances, including any underlying assumptions, are forward- looking statements. The words “anticipate,” “believe,” “continue,” “could,” “estimate,” “expect,” “intend,” “may,” “might,” “plan,” “possible,” “potential,” “predict,” “project,” “should,” “would” and similar expressions may identify forward-looking statements, but the absence of these words does not mean that statement is not forward looking. Forward-looking statements are based on current expectations and assumptions that, while considered reasonable by MoonLake and its management, as the case may be, are inherently uncertain. New risks and uncertainties may emerge from time to time, and it is not possible to predict all risks and uncertainties. Actual results could differ materially from those anticipated in such forward-looking statements as a result of various risks and uncertainties, which include, without limitation, risks and uncertainties associated with MoonLake’s business in general and limited operating history, difficulty enrolling patients in clinical trials, state and federal healthcare reform measures that could result in reduced demand for MoonLake’s product candidates and reliance on third parties to conduct and support its preclinical studies and clinical trials and the other risks described in or incorporated by reference into MoonLake’s Annual Report on Form 10-K for the year ended December 31, 2023 and subsequent filings with the Securities and Exchange Commission. Nothing in this press release should be regarded as a representation by any person that the forward-looking statements set forth herein will be achieved or that any of the contemplated results of such forward-looking statements will be achieved. You should not place undue reliance on forward-looking statements in this press release, which speak only as of the date they are made and are qualified in their entirety by reference to the cautionary statements herein. MoonLake does not undertake or accept any duty to release publicly any updates or revisions to any forward-looking statements to reflect any change in its expectations or in the events, conditions or circumstances on which any such statement is based. MoonLake Immunotherapeutics Investors Matthias Bodenstedt, CFO info@moonlaketx.com MoonLake Immunotherapeutics Media Patricia Sousa media@moonlaketx.com ICR Consilium Mary-Jane Elliott, Namrata Taak, Ashley Tapp Tel: +44 (0) 20 3709 5700 MoonLake@consilium-comms.com

Findings demonstrate ability of PM359 to correct disease-causing mutation in CGD patient blood stem cells, leading to restored immune function in vivo with no off-target edits detected IND for PM359 recently cleared by U.S. FDA; data support advancement into Phase 1/2 clinical trial CAMBRIDGE, Mass., May 08, 2024 (GLOBE NEWSWIRE) -- Prime Medicine, Inc. (Nasdaq: PRME), a biotechnology company committed to delivering a new class of differentiated, one-time curative genetic therapies, today reported new preclinical data demonstrating the ability of its ex vivo Prime Editing program, PM359, to correct a common disease-causing mutation of chronic granulomatous disease (CGD). The data will be presented today at an oral presentation during the American Society of Cell & Gene Therapy 27th Annual Meeting in Baltimore. Prime Medicine recently announced that the U.S. Food and Drug Administration (FDA) has cleared its investigational new drug (IND) application for PM359 for the treatment of CGD. “These data are incredibly exciting—showing for the first time that Prime Editing can not only correct the disease-causing mutation of CGD in human blood stem cells, but that those cells can produce neutrophils with restored immune function and healthy activity following engraftment in rodents with no off-target edits observed,” said Jennifer Gori, Ph.D., Vice President, Head of Hematology and Immunology at Prime Medicine. “Further, we were able to demonstrate clinical-scale production of Prime Edited blood stem cells, supporting our planned advancement into the clinic with PM359.” CGD is a rare inherited disease that leads to recurrent, debilitating and often life-threatening infections. CGD is caused by mutations in any one of the subunits comprising the NADPH oxidase complex, an enzyme that kills bacteria and fungi to control infection. CGD causative mutations are estimated to occur in between one in 100,000 and one in 200,000 births in the U.S., and most children are diagnosed within the first three years of life. The second most common form of CGD, which represents approximately 25% of cases, is caused by loss-of-function mutations in both copies of the NCF1 gene encoding the p47phox protein. Prime Medicine is advancing an ex vivo Prime Editing program, PM359, that aims to correct the predominant mutation in NCF1 in CGD patient CD34+ hematopoietic stem cells (HSCs) and restore NADPH oxidase function. In today’s presentation at ASGCT, Prime Medicine highlighted data from a series of in vivo non-clinical studies using human CGD patient CD34+ HSCs. Notably, findings demonstrated restoration of neutrophil function after stem cell engraftment in mice, as well as the ability to scale up production of Prime Edited cells to clinical scale. Detailed findings are as follows: Prime Editing precisely corrected the CGD causative mutation in greater than 75% of CGD patient CD34+ cellsThe CGD causative mutation is corrected in ≧80% Prime Edited CGD patient CD34+ cells that engraft the bone marrow in a mouse modelNADPH oxidase activity was restored in bone marrow neutrophils in the mice engrafted with Prime Edited CGD patient CD34+ cellsInterferon-regulated gene expression in Prime Edited CGD patient cells was reduced compared to unedited CGD patient cells and similar to healthy donor cells, suggesting Prime Editing restored cells to healthy stateNo unintended or off-target edits were detected in engrafted Prime Edited CGD patient CD34+ cellsProcess development supported reproducible and efficient manufacturing of clinical-scale healthy donor drug products (HDDP) with high purity, viability, potency and Prime Editing efficiency Long-term engraftment of HDDP was achieved with human multilineage blood production and biodistribution maintained “We are very pleased to report these data from our PM359 program in CGD, which supported the basis of our IND application package to the U.S. FDA,” said Jeremy Duffield, M.D., Ph.D., Chief Scientific Officer of Prime Medicine. “With our recent IND clearance, we are working efficiently to move forward with our Phase 1/2 clinical trial of PM359, from which we expect to report first-in-human data in 2025. This is a significant moment for Prime Medicine and the gene editing field, and I am grateful for the unwavering commitment of my colleagues to advance this program. I look forward to the planned evaluation of PM359 in the clinic so that we can truly realize the impact this novel technology may have on patients in need of new treatments.” Presentation Details: Presentation Name: Development of a Prime Edited CD34+ cell Drug Product for the Treatment of P47phox Chronic Granulomatous Disease Date & Time: Wednesday, May 8, 2024, 5:15 p.m. ETPresenter: Jennifer Gori, Ph.D. About PM359PM359, Prime Medicine’s first product candidate within its hematology and immunology area of focus, targets the p47phox variant of chronic granulomatous disease (CGD), a serious, life-threatening disease that presents in childhood. PM359 comprises autologous hematopoietic stem cells (HSCs) modified ex vivo using Prime Editors that have been designed to correct a high percentage of cells containing the disease-causing mutation. PM359 has received rare pediatric drug designation and orphan drug designation from the U.S. Food and Drug Administration. About Chronic Granulomatous Disease (CGD)Chronic granulomatous disease (CGD) is a rare inherited hematologic disorder characterized by susceptibility to severe, difficult-to-treat infections, and inflammatory/autoimmune complications. CGD is caused by mutations in any one of the subunits comprising the NADPH oxidase complex, which is required for phagocytic cells, in particular neutrophils, to destroy many invasive microorganisms. CGD causative mutations are estimated to occur between one in 100,000 and one in 200,000 births in the United States, and most children are diagnosed within the first three years of life. Beginning in childhood, patients with CGD develop infections from a range of both typical and unusual bacteria, fungi and mycobacteria. These infections may present in various organ systems, and protracted infections can lead to long-term organ damage and failure. In addition, patients have non-infectious inflammatory disease, most commonly presenting as inflammatory bowel disease, soft tissue granulomas, and strictures of the urinary or digestive tract. Undiagnosed or untreated, the infectious manifestations of CGD are rapidly fatal, with refractory or antimicrobial resistant infection the leading cause of mortality. About Prime MedicinePrime Medicine is a leading biotechnology company dedicated to creating and delivering the next generation of gene editing therapies to patients. The Company is deploying its proprietary Prime Editing platform, a versatile, precise and efficient gene editing technology, to develop a new class of differentiated one-time curative genetic therapies. Designed to make only the right edit at the right position within a gene while minimizing unwanted DNA modifications, Prime Editors have the potential to repair almost all types of genetic mutations and work in many different tissues, organs and cell types. Taken together, Prime Editing’s versatile gene editing capabilities could unlock opportunities across thousands of potential indications. Prime Medicine is currently progressing a diversified portfolio of investigational therapeutic programs organized around core areas of focus: hematology and immunology, liver, lung, ocular and neuromuscular. Across each core area, Prime Medicine’s initial focus is on genetic diseases with a fast, direct path to treating patients, and those with high unmet need not currently addressable using other gene editing approaches. Over time, the Company intends to maximize Prime Editing’s broad and versatile therapeutic potential to expand beyond the genetic diseases in its initial pipeline, potentially including immunological diseases, cancers, infectious diseases, and targeting genetic risk factors in common diseases, which collectively impact millions of people. For more information, please visit www.primemedicine.com. Forward Looking StatementsThis press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including, without limitation, implied and express statements about Prime Medicine’s beliefs and expectations regarding: the potential of PM359 to correct a causative mutation of CGD; its expectations regarding the breadth and potential of Prime Editing technology; the anticipated maturation into a clinical-stage company by bringing PM359 into clinical development in 2024 with initial data expected in 2025; and the potential for Prime Editors to repair genetic mutations and offer curative genetic therapies for a wide spectrum of diseases. The words “may,” “might,” “will,” “could,” “would,” “should,” “expect,” “plan,” “anticipate,” “intend,” “believe,” “expect,” “estimate,” “seek,” “predict,” “future,” “project,” “potential,” “continue,” “target” and similar words or expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Any forward-looking statements in this press release are based on management’s current expectations and beliefs and are subject to a number of risks, uncertainties and important factors that may cause actual events or results to differ materially from those expressed or implied by any forward-looking statements contained in this press release, including, without limitation, risks associated with: uncertainties related to Prime Medicine’s product candidates entering clinical trials; the authorization, initiation, and conduct of preclinical and IND-enabling studies and other development requirements for potential product candidates, including uncertainties related to opening INDs and obtaining regulatory approvals; risks related to the development and optimization of new technologies, the results of preclinical studies, or clinical studies not being predictive of future results in connection with future studies; the scope of protection Prime Medicine is able to establish and maintain for intellectual property rights covering its Prime Editing technology; Prime Medicine’s ability to identify and enter into future license agreements and collaborations; and general economic, industry and market conditions, including rising interest rates, inflation, and adverse developments affecting the financial services industry. These and other risks and uncertainties are described in greater detail in the section entitled “Risk Factors” in Prime Medicine’s most recent Annual Report on Form 10-K, as well as any subsequent filings with the Securities and Exchange Commission. In addition, any forward-looking statements represent Prime Medicine’s views only as of today and should not be relied upon as representing its views as of any subsequent date. Prime Medicine explicitly disclaims any obligation to update any forward-looking statements subject to any obligations under applicable law. No representations or warranties (expressed or implied) are made about the accuracy of any such forward-looking statements. Investor ContactHannah DeresiewiczStern Investor Relations, Inc.212-362-1200hannah.deresiewicz@sternir.com Media ContactDan Budwick, 1ABdan@1ABmedia.com