CR1

ROCKVILLIE, Md. and SUZHOU, China, March 18, 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 and other major diseases, today announced that the primary endpoint has been met in the second Phase 2 clinical study of efdamrofusp alfa high-dose, a recombinant human VEGFR-Fc-Human CR1 fusion protein injection (R&D code: IBI302), in Chinese subjects with neovascular age-related macular degeneration (nAMD). According to the results of the two Phase 2 clinical studies conducted in more than 360 subjects of nAMD, compared with Aflibercept, IBI302 can be administrated in long-interval (every 12 weeks), while providing a stable and robust visual benefit and anatomic improvements, as well as potential inhibition effect in macular atrophy. Based on those results, Innovent advanced IBI302 8mg into a Phase 3 clinical study STAR in October 2023. This was a randomized, double-masked, active-controlled Phase 2 clinical study (NCT05403749), evaluating the longer interval of intravitreal injection of high-dose IBI302 in subjects with nAMD. A total of 132 subjects were randomized 1: 1: 1 to IBI302 6.4 mg group, IBI302 8.0 mg group, or Aflibercept 2.0 mg group. After the loading therapy, subjects in IBI302 6.4 mg group and 8.0 mg group were dosed with adjusted intervals of every 8 weeks (Q8W) or every 12 weeks (Q12W), depending on response to loading therapy. Subjects in Aflibercept 2.0 mg group were dosed Q8W after the loading therapy. The primary endpoint was the change in best corrected visual acuity (BCVA) in the study eye from baseline to week 40. The study lasted for 52 weeks. The results showed that the primary endpoint was successfully met: at week 40, the IBI302 6.4 mg and 8.0 mg groups showed non-inferior BCVA gains to the Aflibercept 2.0 mg group. The mean BCVA improvement from baseline was 10.5 ETDRS letters for the IBI302 6.4 mg group, 11.0 ETDRS letters for the IBI302 8.0 mg group, and 9.8 ETDRS letters for the Aflibercept 2.0 mg group at week 40. The mean change from baseline in central subfield thickness (CST) was -163.19 μm for the IBI302 6.4 mg group, -184.46 μm for the IBI302 8.0 mg group, and -108.23 μm for the Aflibercept 2.0 mg group at week 40. In addition, approximately 81%, 88% of subjects in 6.4 mg IBI302 groups and 8.0mg IBI302 groups respectively were able to extend dosing interval to Q12W, similar to that in the proportion of subjects dosed Q12W or longer with Aflibercept 8.0 mg (83% in PULSAR trial)1 or Faricimab (TENAYA & LUCERNE trial, with 79.7% and 77.8% respectively)2 by indirect comparison. Based on the excellent long-interval dosing performance in the Phase 2 studies, the Phase 3 study STAR added Q16W dosing interval regimen for IBI302. The overall safety profile of IBI302 was favorable, comparable to Aflibercept 2.0 mg, and consistent with previous studies. No new safety signals were identified. Detailed study data will be further analyzed and published in the near future. Professor Xiaodong Sun, Principal Investigator of the Study, Head of National Center for Clinical Ophthalmology, Shanghai General Hospital, stated: "Intravitreal injection of anti-VEGF drugs is currently the first-line treatment for nAMD, but there are still unmet clinical needs given their frequent intravitreal injection and gradual loss of visual benefits. Exploring longer interval dosing and anti-macular atrophy are necessary and urgent. IBI302 is a global first-in-class anti-VEGF-anti-complement bispecific molecule. As the principal investigator for IBI302 trials, I am very pleased to see that this Phase 2 study met the primary endpoint and demonstrated the potential for long-interval dosing. These results will be further validated in the pivotal trial of IBI302. I look forward to providing a new treatment option for nAMD patients." Dr. Lei Qian, Vice President of Clinical Development of Innovent, stated: "There are two major trends in drug development for nAMD: extending dosing intervals and reducing the occurrence of macular atrophy. In the results of two Phase 2 studies, which enrolled over 360 subjects, IBI302 improved BCVA and macular edema in patients with nAMD significantly, extended dosing intervals, and had the potential to prevent the development of macular atrophy. Next, we will further investigate the long-interval dosing efficacy and safety of high-dose IBI302 in the Phase 3 STAR trial, hoping to bring a new generation of anti-VEGF agents to patients with nAMD." About neovascular age-related macular degeneration (nAMD) Age-related macular degeneration (AMD) is a progressive ocular disease involving the macular retina, leading to central visual impairment, the incidence of which increases with age. Neovascular age-related macular degeneration (nAMD) is one of the major forms of AMD, accounting for 15% to 20% of all AMD patients and is the leading cause of central vision loss in AMD patients over 65 years3. The incidence of AMD is increasing year by year in China, and it has become the third leading cause of blindness in China. The pathogenesis of nAMD has not been fully elucidated. It is generally accepted that angiogenesis induced by increased expression of VEGF is the main cause of nAMD, and inflammatory reaction mediated by abnormal activation of complement is also considered to be an important cause of AMD. Ocular anti-VEGF agents have led to significant visual benefits and changed the course of nAMD, but the frequent dosing (every 4 or 8 weeks) currently places a heavy burden on patients, families and society. In addition, the visual benefits of anti-VEGF drug therapy are gradually diminished year by year. In approximately two thirds of nAMD patients with a follow-up for over 7 years, the visual gains from anti-VEGF treatment significantly diminish4. Macular atrophy or retinal fibrosis are important causes of vision loss after long-term anti-VEGF therapy. Currently, drug development for nAMD is mainly focusing on extending the dosing intervals, and there are few drugs under investigation for macular atrophy or retinal fibrosis. Two drugs targeting complement have been approved by the US FDA in 20235,6 for the treatment of geographic atrophy secondary to dry AMD. About Efdamrofusp Alfa (IBI302) IBI302 is a recombinant fully human bispecific fusion protein of Innovent Biologics with global proprietary rights. The N-terminus is a VEGF domain that can bind to the VEGF family, block VEGF-mediated signaling pathway, inhibit vascular epithelium proliferation and angiogenesis, and improve vasopermeability and reduce leakage. The C-terminus of IBI302 is the complement binding domain that can inhibit the activation of the classic pathway and alternative pathway of complement through the specific binding of C3b and C4b, and reduce the inflammatory response mediated by the complement. IBI302 may exert its therapeutic effect by inhibiting both VEGF-mediated angiogenesis and complement activation pathways. About Innovent Innovent is a leading biopharmaceutical company founded in 2011 with the mission to provide high-quality biologics that are affordable to all. The company discovers, develops, manufactures and commercializes innovative medicines that treat some of the most intractable diseases. Its pioneering therapies to treat cancer, cardiovascular and metabolic, autoimmune and eye diseases. Innovent has 10 products in the market, 3 new drug applications under the NMPA review, 5 assets in Phase 3 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. SOURCE Innovent Biologics

– Kriya anticipates up to 5 programs to enter clinic by the end of 2025 – – Current pipeline of gene therapies for common diseases spans three major therapeutics areas: ophthalmology, metabolic disease and neurology – – Company enters 2024 with cash balance of $325 million and runway into late 2026 – PALO ALTO, Calif. and RESEARCH TRIANGLE PARK, N.C., Jan. 08, 2024 (GLOBE NEWSWIRE) -- Kriya Therapeutics, Inc., ("Kriya") a biopharmaceutical company developing gene therapies for common diseases affecting millions of people around the world, today provided an update on its pipeline of gene therapies for prevalent conditions including geographic atrophy, thyroid eye disease, diabetes, NASH, trigeminal neuralgia and epilepsy. Kriya is advancing the first of its gene therapy product candidates into the clinic in 2024 and expects up to five programs in the clinic by the end of 2025. "Our mission is to revolutionize the field of medicine by delivering transformative, one-time gene therapies to patients suffering from common diseases," said Shankar Ramaswamy, M.D., Co-Founder and CEO of Kriya. "In parallel with our near-term goal of advancing up to five gene therapies into the clinic by the end of 2025, we remain deeply committed to our vision of significantly reducing the cost of manufacturing gene therapies through innovations in process sciences and product engineering.” Kriya's platform includes an end-to-end gene therapy product development engine that integrates cutting-edge research and computational biology with a scalable GMP manufacturing facility deploying next-generation processes and analytical characterization techniques. Kriya’s pipeline includes gene therapies across three major therapeutic areas: ophthalmology, metabolic disease and neurology. Its programs share the following features: direct-to-tissue delivery, validated biology, de-risked clinical and regulatory paths and large commercial markets. Kriya’s publicly disclosed programs are summarized below. Dr. Ramaswamy will share further information on Kriya’s portfolio during his presentation at the J.P. Morgan 42nd Annual Healthcare Conference on Tuesday, January 9th at 9:00 AM PT in San Francisco, California. Ophthalmology ProgramsGeographic Atrophy (GA): KRIYA-825 is designed as a one-time gene therapy expressing a fusion protein inhibiting complement C3 and C5, delivered by an in-office suprachoroidal injection with the objective of slowing GA lesion growth and vision loss. GA affects approximately two million people in the United States and the European Union. Existing treatment options require monthly or bimonthly physician-administered intravitreal injections that can be burdensome for patients. Kriya has designed KRIYA-825 for GA with the following potential goals in mind: Robust complement inhibition: A novel complement receptor 2 -complement receptor 1 (CR2-CR1) fusion protein—where the CR1 domain is designed to block the function of both C3 and C5, while the CR2 domain is designed to bind to cell surfaces where complement fragments deposit and cause damage;Multi-year durability: Adeno-associated virus (AAV)-mediated continuous expression of CR2-CR1 fusion protein following a one-time injection to eliminate the need for frequent intravitreal injections as required by currently available therapies for GA; andTargeted delivery: One-time suprachoroidal injection with the goal of achieving transduction of retinal cells while minimizing inflammation and overall patient burden. Thyroid Eye Disease (TED): KRIYA-586 is designed as a one-time gene therapy expressing an antibody blocking insulin-like growth factor-1 receptors (IGF-1R), delivered by an in-office peribulbar injection with the objective of reducing proptosis and diplopia as well as other key features of TED. Approximately one million people in the United States and the European Union have TED. The only FDA-approved treatment is an intravenously administered monoclonal antibody that works by blocking IGF-1R. Kriya has designed KRIYA-586 for TED with the following potential goals in mind: Minimized treatment burden: One-time, in-office peribulbar injection to eliminate the burdensome requirement for multiple infusions or injections;Focal delivery: Localized antibody expression in extraocular muscles and fat tissue to limit the potential for side effects that can be observed with systemically administered therapies; andLong-term durability: AAV-mediated antibody expression to deliver sustained improvements in proptosis and diplopia as well as other key manifestations of TED. For more information on Kriya's Ophthalmology programs, please visit the Ophthalmology page of our website. Metabolic Disease ProgramsDiabetes: KRIYA-839 is designed as a one-time gene therapy expressing insulin and glucokinase, delivered intramuscularly with the objective of driving durable glycemic control and reducing or eliminating the need for exogenous insulin. Of the approximately 90 million people in the United States and the European Union who have type 1 and type 2 diabetes, 17 million use insulin to manage their disease. Current treatments for type 1 diabetes require burdensome chronic insulin injections and constant treatment modification based on dietary intake and blood glucose monitoring. Kriya has designed KRIYA-839 for diabetes with the following potential goals in mind: Robust glycemic control: Improving time-in-range and lowering HbA1c to reduce the risk of long-term diabetic complications;Insulin independence: Enabling patients to achieve insulin independence while maintaining robust glycemic control; andMinimized treatment burden: Substantially reducing or eliminating the need for multiple daily injections of insulin with a one-time treatment. Nonalcoholic Steatohepatitis (NASH): KRIYA-497 is designed as a one-time gene therapy expressing the native FGF21 protein, delivered intramuscularly with the objective of reducing fibrosis, reversing steatosis, and improving the overall metabolic profile of patients with later stages of NASH with liver predominant pathology (F3 and compensated F4). NASH affects approximately 40 million people in the United States and the European Union. There are currently no FDA-approved therapies for the treatment of NASH. Kriya has designed KRIYA-497 for NASH with the following potential goals in mind: Robust anti-fibrotic activity: Expression of native FGF21 protein to drive natural ligand/receptor interactions and enhance biodistribution across multiple organs;Minimized treatment burden: One-time intramuscularly administered therapy to reduce complexity for patients who are often taking multiple other concomitant therapies; andContinuous expression: Consistent concentration of native FGF21 protein to limit Cmax-mediated gastrointestinal issues. For more information on Kriya's Metabolic Disease programs, please visit the Metabolic Disease page of our website. Neurology ProgramsTrigeminal Neuralgia (TN): KRIYA-748 is designed as a one-time gene therapy expressing a chemogenetically-gated ion channel, delivered through an injection into the trigeminal nerve with the objective of reducing the frequency and severity of debilitating paroxysmal pain attacks. Once expressed in the nerve, the channel is designed to selectively open in the presence of the orally-administered CNS-penetrant small molecule, varenicline (the FDA-approved generic medication for smoking cessation originally marketed under the brand name "Chantix®"), leading to the passage of chloride ions and reduced excitation of target neurons. Trigeminal Neuralgia affects approximately 400,000 people in the United States and the European Union. Current treatments include anticonvulsants, which can have significant tolerability issues and waning efficacy over time. Kriya has designed KRIYA-748 for trigeminal neuralgia with the following potential goals in mind: Pain reduction: Goal of reducing the frequency and severity of pain attacks by focally inhibiting neuronal hyperexcitability in the trigeminal nerve;Long-term durability: One-time administration of gene therapy to eliminate the need for cycling through anti-epileptic medications and surgical procedures; andRegulatable activity: Targeted delivery to the trigeminal nerve, additionally engineered with the ability to “turn off” the gene therapy through withdrawal of the orally-administered small molecule, varenicline. Focal Epilepsy: KRIYA-382 is designed as a one-time gene therapy expressing a chemogenetically-gated ion channel, delivered through a direct injection into epileptic foci within the brain with the objective of reducing the frequency and severity of seizures. Kriya’s epilepsy gene therapy uses a similar chemogenetic technology as is utilized in its trigeminal neuralgia program, described above. Focal epilepsy affects close to 5 million people in the United States and the European Union. Current treatments include first- and second-line antiseizure medications. A significant proportion of patients suffer from refractory epilepsy, many of whom are candidates for invasive neurosurgery. Kriya has designed KRIYA-382 for focal epilepsy with the following potential goals in mind: Seizure reduction: Goal of minimizing seizures by inhibiting neuronal hyperexcitability at epileptic foci;Long-term durability: One-time administration of gene therapy designed to eliminate the need for cycling through anti-epileptic medications; andRegulatable activity: Targeted delivery to epileptic foci, additionally engineered with the ability to “turn off” the gene therapy through withdrawal of the orally-administered small molecule, varenicline. For more information on Kriya's Neurology programs, please visit the Neurology page of our website. About Kriya TherapeuticsOur mission is to revolutionize medicine, with the ultimate goal of eliminating human suffering and enabling people to live without the burden of disease. Kriya is a biopharmaceutical company developing gene therapies to address common diseases affecting millions of people around the world. With operations in Palo Alto, California and Research Triangle Park, North Carolina, Kriya has raised over $600 million, which will be used to advance a broad pipeline of gene therapies for ophthalmology, metabolic disease and neurology. For more information, please visit www.kriyatx.com and follow us on LinkedIn and X.

Currently, a lot is known about which genes are responsible for our individual blood groups, however not much is understood about how and why the levels of the blood group molecules differ between one person and another. This can be important for blood transfusion safety. Now a research group has developed a toolbox that finds the answer – and in doing so, has solved a 50-year-old mystery. Currently, a lot is known about which genes are responsible for our individual blood groups, however not much is understood about how and why the levels of the blood group molecules differ between one person and another. This can be important for blood transfusion safety. Now a research group at Lund University in Sweden has developed a toolbox that finds the answer -- and in doing so, has solved a 50-year-old mystery. The study was published recently in Nature Communications. For the past 30 years, the research group in Lund has studied the genetic basis of our many blood groups and their research has laid the foundation of six new blood group systems. On the surface of the red blood cell are found proteins and carbohydrates that are very similar between people. However, small differences in these molecules have been shown to be due to genetic variants that encode what we know as blood group antigens. What has not been understood until now is why people with the same blood group can have different amounts of a certain blood group antigen on their red blood cells. "This is important, because if you only have a couple of hundred blood group molecules per cell instead of a thousand or even a million molecules, then there is a risk that they maybe missed in a blood compatibility test, which can affect the safety of a blood transfusion," explains Martin L Olsson, professor in Transfusion Medicine at Lund University, and consultant within Clinical Immunology and Transfusion Medicine, Region Skåne, who has led the project. Since routine genetic analysis could not answer this question, the research group turned its attention to a group of proteins called transcription factors. These are molecules that can recognise different "landing" sites in DNA and work a little like a light switch to turn off/turn down genes or get them to express more strongly. Thus, transcription factors are important for the production of different proteins in the cells. With the help of a series of bioinformatics tools (together called a pipeline) developed by PhD student, Gloria Wu, the researchers could localise nearly 200 landing sites for transcription factors in 33 different blood group genes in our DNA. Then, to test the pipeline to see if the predictions were correct, the group investigated one of the most important transcription factors for red blood cell development to see if there was a genetic change in one of these landing sites. This could give the reason for why a certain blood group was downregulated to a low level. Tested on an unsolved blood group mystery To see how the results could be used, the researchers focused on a blood group variant called Helgeson, in which the red blood cell has unusually little of a molecule called Complement Receptor 1 (CR1), an important protein for our immune response. The Helgeson blood group has been a mystery that has eluded the research world for a long time. Approximately 1% of the population has this blood group but it hasn't even been possible to detect it with the help of DNA techniques. In addition, the mechanism behind the low CR1 expression has remained unexplained. "Margaret Helgeson was a medical technologist in Minneapolis in the 1970s who was trying to find compatible blood for a patient in need of a blood transfusion. Despite her best efforts she could not find any suitable blood units. In desperation, she tested her own blood, and to her surprise, found it to be a match," recounted Jill Storry, adjunct professor of experimental transfusion medicine at Lund University and one of the researchers behind the study. This is how the blood group became known as Helgeson. But why does a small group of people have this weak blood group? It turns out that blood donors and patients with the Helgeson blood group have a low CR1 expression because of a genetic variation in the landing site DNA sequence for an important transcription factor. This means the transcription factor cannot bind where it should and drive the production of CR1. "Now the gene simply idles. In our study, we also showed this genetic variant to be more common in Thai blood donors compared with Swedish blood donors, which makes sense since we know from previous studies that a lower CR1 level is protective against malaria," explains Martin L Olsson. So, while it's difficult to detect a lower expression of CR1 in the transfusion laboratory, it gives protection against malaria, especially in areas such as Southeast Asia where the disease is common. Thanks to this study, we now understand the mechanisms behind the Helgeson blood group and why it can be more difficult to detect in certain populations. "Based on what we know now, we can improve the laboratory tests. Our goal is to update the existing DNA-based chip that is used for blood group tests with the new variant, which will result in a safer diagnostic test," says Gloria Wu. The role of blood groups in disease is the next step With the help of this data-driven, bioinfomatic pipeline, which makes it possible to get a comprehensive grip on how our blood group genes are regulated, the research group can continue to apply more of their findings to other blood groups. Furthermore, the toolbox can be utilised more widely. "Much of our research on blood groups now uses a combination of data-based predictive tools that can point us to the right experiment to test in the lab. The next challenge is to better understand the function of blood groups by connecting the information from large databases on how diseases affect people differently depending on their blood group," concludes Martin L Olsson.