Common Cold

Intratumoral delivery of HSV-1 encoded IL-12 and IL-2 enhanced local and systemic effector T-cell responses in cold tumor preclinical modelPITTSBURGH, April 04, 2024 (GLOBE NEWSWIRE) -- Krystal Biotech, Inc. (the “Company”) (NASDAQ: KRYS), a commercial-stage biotechnology company, announced today that the Company will be presenting new preclinical data on local and systemic immune activation following intratumoral injection of the Company’s platform technology encoding murine interleukin-12 (IL-12) and interleukin-2 (IL-2), the species matched equivalent to the Company’s clinical-stage oncology product candidate KB707, at the American Association for Cancer Research (AACR) 2024 Annual Meeting being held from April 5-10, 2024 in San Diego, California. Poster presentation details are as follows: Title: An HSV-1-based vector for local delivery of IL-12 and IL-2 reshapes the immune landscape leading to tumor clearance and systemic immune surveillancePresenter: Dana Previte, PhD Session: Vector Systems, Oncolytic Virotherapy, and Gene TherapyDate and Time: April 10, 2024 from 9:00AM to 12:30PM PTPresentation Number: 7260 The poster will be available to conference attendees. Following the presentation, the poster will also be available to view online on the Investor section of the Company’s website. About IL-2 and IL-12 and KB707IL-2 and IL-12 are secreted cytokines with complementary functions promoting cell-mediated immunity in humans. Both IL-2 and IL-12 have been shown to elicit anti-tumor immune responses in preclinical models and in clinical settings and have been extensively studied for their potential in cancer immunotherapy. Despite promising signs of efficacy, it has proven difficult to effectively harness IL-2 and IL-12 for therapeutic benefit, as systemic administration is often poorly tolerated, and their inherently short half-lives necessitate high dose levels and extremely frequent dose intervals. KB707 is a modified HSV-1 vector designed to deliver genes encoding both human IL-12 and IL-2 directly to a patient’s tumor(s) and promote systemic immune-mediated tumor clearance. KB707 targets solid tumors that are accessible via intratumoral injection or inhalation. About Krystal Biotech, Inc.Krystal Biotech, Inc. (NASDAQ: KRYS) is a commercial-stage biotechnology company focused on the discovery, development and commercialization of genetic medicines to treat diseases with high unmet medical needs. VYJUVEK® is the Company’s first commercial product, the first-ever redosable gene therapy, and the first medicine approved by the FDA for the treatment of dystrophic epidermolysis bullosa. The Company is rapidly advancing a robust preclinical and clinical pipeline of investigational genetic medicines in respiratory, oncology, dermatology, ophthalmology, and aesthetics. Krystal Biotech is headquartered in Pittsburgh, Pennsylvania. For more information, please visit http://www.krystalbio.com, and follow @KrystalBiotech on LinkedIn and X (formerly Twitter). CONTACTInvestors and Media: Meg Dodge Krystal Biotech mdodge@krystalbio.com

Approval of first-in-class, oral, Factor D inhibitor based on results from pivotal ALPHA Phase III trial WILMINGTON, Del.--(BUSINESS WIRE)-- VOYDEYA™ (danicopan) has been approved in the US as add-on therapy to ravulizumab or eculizumab for the treatment of extravascular hemolysis (EVH) in adults with paroxysmal nocturnal hemoglobinuria (PNH).1 VOYDEYA is a first-in-class, oral, Factor D inhibitor developed as an add-on to standard-of-care ULTOMIRIS® (ravulizumab-cwvz) or SOLIRIS® (eculizumab) to address the needs of the approximately 10-20% of patients with PNH who experience clinically significant EVH while treated with a C5 inhibitor.2,3 The approval by the US Food and Drug Administration (FDA) was based on positive results from the pivotal ALPHA Phase III trial. Results from the 12-week primary evaluation period of the trial were published in The Lancet Haematology.2 Bart Scott, MD, Professor, Division of Hematology and Oncology at the University of Washington Medical Center, and Professor, Clinical Research Division at Fred Hutchinson Cancer Center, said: “The approval of VOYDEYA offers this small subset of PNH patients an add-on therapy designed to address EVH, while maintaining disease control with ULTOMIRIS or SOLIRIS. Terminal complement inhibition with ULTOMIRIS can address the life-threatening complications of PNH, building on the efficacy and safety of SOLIRIS established over nearly 20 years.” Marc Dunoyer, Chief Executive Officer, Alexion, said: “The approval of first-in-class, Factor D inhibitor VOYDEYA marks an important advancement in the treatment of PNH and builds on our leadership and commitment to bring forward innovation in complement science. As the ALPHA trial suggests, dual complement pathway inhibition at Factor D and C5 may be an optimal treatment approach for this subset of patients with EVH, enabling them to continue with proven standard-of-care therapy.” The ALPHA Phase III trial evaluated the efficacy and safety of VOYDEYA as add-on to ULTOMIRIS or SOLIRIS in patients with PNH who experienced clinically significant EVH. Results showed that VOYDEYA met the primary endpoint of change in hemoglobin from baseline to week 12 and all key secondary endpoints, including transfusion avoidance and change in Functional Assessment of Chronic Illness Therapy – Fatigue (FACIT-Fatigue) score.2 Results from the ALPHA Phase III trial showed VOYDEYA was generally well tolerated, and no new safety concerns were identified. In the trial, the most common treatment-emergent adverse events were headache, nausea, arthralgia and diarrhea.2 VOYDEYA has been granted Breakthrough Therapy designation by the US FDA and PRIority MEdicines (PRIME) status by the European Medicines Agency. VOYDEYA has also been granted Orphan Drug Designation in the US, European Union (EU) and Japan for the treatment of PNH. VOYDEYA has been approved in Japan and recommended for approval in the EU. Regulatory reviews are ongoing in additional countries. INDICATION & IMPORTANT SAFETY INFORMATION FOR VOYDEYA™ (danicopan) INDICATION What is VOYDEYA? VOYDEYA is a prescription medicine used along with ravulizumab or eculizumab to treat breakdown of red blood cells that takes place outside of blood vessels (extravascular hemolysis), in adults with paroxysmal nocturnal hemoglobinuria (PNH). It is not known if VOYDEYA is safe and effective in children. IMPORTANT SAFETY INFORMATION What is the most important information I should know about VOYDEYA? VOYDEYA is a medicine that affects your immune system. VOYDEYA may lower the ability of your immune system to fight infections. VOYDEYA increases your chance of getting serious infections caused by encapsulated bacteria. These serious infections may quickly become life-threatening and cause death if not recognized and treated early. You must complete or update meningococcal vaccine(s) and streptococcus vaccine(s) at least 2 weeks before your first dose of VOYDEYA. If you have not completed your vaccinations and VOYDEYA must be started right away, you should receive the required vaccinations as soon as possible. If you have not been vaccinated at least 2 weeks before your first VOYDEYA dose and VOYDEYA must be started right away, you should also receive antibiotics to take for as long as your healthcare provider tells you. If you have been vaccinated against these bacteria in the past, you might need additional vaccinations before starting VOYDEYA. Your healthcare provider will decide if you need additional vaccinations. Vaccines do not prevent all infections caused by encapsulated bacteria. Call your healthcare provider or get emergency medical care right away if you have any of these signs and symptoms of a serious infection: fever with or without chills, fever and a rash, fever with chest pain and cough, fever with breathlessness/fast breathing, fever with high heart rate, headache with nausea or vomiting, headache and a fever, headache with a stiff neck or stiff back, confusion, body aches with flu-like symptoms, clammy skin, eyes sensitive to light. Your healthcare provider will give you a Patient Safety Card about the risk of serious infections. Carry it with you at all times during treatment and for 1 week after your last VOYDEYA dose. Your risk of serious infections may continue for a few days after your last dose of VOYDEYA. It is important to show this card to any healthcare provider who treats you. This will help them diagnose and treat you quickly. VOYDEYA is only available through a program called the VOYDEYA Risk Evaluation and Mitigation Strategy (REMS). Before you can take VOYDEYA, your healthcare provider must: enroll in the VOYDEYA REMS; counsel you about the risk of serious infections caused by certain bacteria; give you information about the symptoms of serious infections; make sure that you are vaccinated against serious infections caused by encapsulated bacteria and that you receive antibiotics if you need to start VOYDEYA right away and you are not up to date on your vaccinations; give you a Patient Safety Card about your risk of serious infections, as discussed above. Who should not receive VOYDEYA? Do not take VOYDEYA if you have a serious infection caused by encapsulated bacteria, including Neisseria meningitidis, Streptococcus pneumoniae, or Haemophilus influenzae type B infection. Before taking VOYDEYA, tell your healthcare provider about all of your medical conditions, including if you: have an infection or fever, have liver problems, are pregnant or plan to become pregnant or are breastfeeding. It is not known if VOYDEYA will harm your unborn baby or if it passes into your breast milk. Do not breastfeed during treatment with VOYDEYA and for 3 days after the last dose. Tell your healthcare provider about all the vaccines you receive and medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements which could affect your treatment. VOYDEYA may affect the way other medicines work. If you stop taking VOYDEYA, your healthcare provider will need to monitor you closely for at least 2 weeks after your last dose. Stopping treatment with VOYDEYA may cause a breakdown of red blood cells due to PNH. Symptoms or problems that can happen due to breakdown of red blood cells include: decreased hemoglobin level in your blood and tiredness. What are the possible side effects of VOYDEYA? VOYDEYA can cause serious side effects including increased liver enzyme levels and increased cholesterol. Your healthcare provider will do blood tests to check your liver enzyme levels and cholesterol before and during treatment with VOYDEYA. Your healthcare provider may temporarily or permanently stop treatment with VOYDEYA if you develop increased liver enzyme levels. The most common side effect of VOYDEYA is headache. Tell your healthcare provider about any side effect that bothers you or that does not go away. These are not all of the possible side effects of VOYDEYA. For more information, ask your healthcare provider or pharmacist. Call your healthcare provider for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. Please see the accompanying full Prescribing Information and Medication Guide for VOYDEYA (danicopan), including Boxed WARNING regarding serious infections caused by encapsulated bacteria. INDICATION(S) & IMPORTANT SAFETY INFORMATION FOR ULTOMIRIS® (ravulizumab-cwvz) INDICATION(S) What is ULTOMIRIS? ULTOMIRIS is a prescription medicine used to treat: adults and children 1 month of age and older with a disease called Paroxysmal Nocturnal Hemoglobinuria (PNH). adults and children 1 month of age and older with a disease called atypical Hemolytic Uremic Syndrome (aHUS). ULTOMIRIS is not used in treating people with Shiga toxin E. coli related hemolytic uremic syndrome (STEC-HUS). adults with a disease called generalized Myasthenia Gravis (gMG) who are anti-acetylcholine receptor (AChR) antibody positive. adults with a disease called Neuromyelitis Optica Spectrum Disorder (NMOSD) who are anti-aquaporin 4 (AQP4) antibody positive. It is not known if ULTOMIRIS is safe and effective in children younger than 1 month of age. It is not known if ULTOMIRIS is safe and effective for the treatment of gMG or NMOSD in children. IMPORTANT SAFETY INFORMATION What is the most important information I should know about ULTOMIRIS? ULTOMIRIS is a medicine that affects your immune system and may lower the ability of your immune system to fight infections. ULTOMIRIS increases your chance of getting serious meningococcal infections that may quickly become life-threatening or cause death if not recognized and treated early. You must complete or update meningococcal vaccine(s) at least 2 weeks before your first dose of ULTOMIRIS. If you have not completed your meningococcal vaccines and ULTOMIRIS must be started right away, you should receive the required vaccine(s) as soon as possible. If you have not been vaccinated and ULTOMIRIS must be started right away, you should also receive antibiotics for as long as your healthcare provider tells you. If you had a meningococcal vaccine in the past, you might need additional vaccines before starting ULTOMIRIS. Your healthcare provider will decide if you need additional meningococcal vaccines. Meningococcal vaccines do not prevent all meningococcal infections. Call your healthcare provider or get emergency medical care right away if you get any of these signs and symptoms of a meningococcal infection: fever, fever with high heart rate, headache and fever, confusion, muscle aches with flu-like symptoms, fever and a rash, headache with nausea or vomiting, headache with a stiff neck or stiff back, or eyes sensitive to light. Your healthcare provider will give you a Patient Safety Card about the risk of serious meningococcal infection. Carry it with you at all times during treatment and for 8 months after your last ULTOMIRIS dose. Your risk of meningococcal infection may continue for several months after your last dose of ULTOMIRIS. It is important to show this card to any healthcare provider who treats you. This will help them diagnose and treat you quickly. ULTOMIRIS is only available through a program called the ULTOMIRIS and SOLIRIS Risk Evaluation and Mitigation Strategy (REMS). Before you can receive ULTOMIRIS, your healthcare provider must: enroll in the REMS program; counsel you about the risk of serious meningococcal infections; give you information about the signs and symptoms of serious meningococcal infection; make sure that you are vaccinated against serious infections caused by meningococcal bacteria, and that you receive antibiotics if you need to start ULTOMIRIS right away and are not up to date on your vaccines; give you a Patient Safety Card about your risk of meningococcal infection. ULTOMIRIS may also increase the risk of other types of serious infections, including Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria gonorrhoeae. Your child should receive vaccines against Streptococcus pneumoniae and Haemophilus influenzae type b (Hib) if treated with ULTOMIRIS. Certain people may be at risk of serious infections with gonorrhea. Who should not receive ULTOMIRIS? Do not receive ULTOMIRIS if you have a serious meningococcal infection when you are starting ULTOMIRIS. Before you receive ULTOMIRIS, tell your healthcare provider about all of your medical conditions, including if you: have an infection or fever, are pregnant or plan to become pregnant, and are breastfeeding or plan to breastfeed. It is not known if ULTOMIRIS will harm your unborn baby or if it passes into your breast milk. You should not breastfeed during treatment and for 8 months after your final dose of ULTOMIRIS. Tell your healthcare provider about all the vaccines you receive and medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements which could affect your treatment. If you have PNH and you stop receiving ULTOMIRIS, your healthcare provider will need to monitor you closely for at least 16 weeks after you stop ULTOMIRIS. Stopping ULTOMIRIS may cause breakdown of your red blood cells due to PNH. Symptoms or problems that can happen due to red blood cell breakdown include: drop in your red blood cell count, tiredness, blood in your urine, stomach-area (abdomen) pain, shortness of breath, blood clots, trouble swallowing, and erectile dysfunction (ED) in males. If you have aHUS, your healthcare provider will need to monitor you closely for at least 12 months after stopping treatment for signs of worsening aHUS or problems related to a type of abnormal clotting and breakdown of your red blood cells called thrombotic microangiopathy (TMA). Symptoms or problems that can happen with TMA may include: confusion or loss of consciousness, seizures, chest pain (angina), difficulty breathing and blood clots or stroke. What are the possible side effects of ULTOMIRIS? ULTOMIRIS can cause serious side effects including infusion-related reactions. Symptoms of an infusion-related reaction with ULTOMIRIS may include lower back pain, abdominal pain, muscle spasms, changes in blood pressure, tiredness, feeling faint, shaking chills (rigors), discomfort in your arms or legs, bad taste, or drowsiness. Stop treatment of ULTOMIRIS and tell your healthcare provider right away if you develop these symptoms, or any other symptoms during your ULTOMIRIS infusion that may mean you are having a serious infusion-related reaction, including: chest pain, trouble breathing or shortness of breath, swelling of your face, tongue, or throat, and feel faint or pass out. The most common side effects of ULTOMIRIS in people treated for PNH are upper respiratory tract infection and headache. The most common side effects of ULTOMIRIS in people treated for aHUS are upper respiratory tract infection, diarrhea, nausea, vomiting, headache, high blood pressure and fever. The most common side effects of ULTOMIRIS in people with gMG are diarrhea and upper respiratory tract infections. The most common side effects of ULTOMIRIS in people with NMOSD are COVID-19 infection, headache, back pain, urinary tract infection, and joint pain (arthralgia). Tell your healthcare provider about any side effect that bothers you or that does not go away. These are not all the possible side effects of ULTOMIRIS. For more information, ask your healthcare provider or pharmacist. Call your healthcare provider right away if you miss an ULTOMIRIS infusion or for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. Please see the accompanying full Prescribing Information and Medication Guide for ULTOMIRIS, including Boxed WARNING regarding serious meningococcal infections. INDICATION(S) & IMPORTANT SAFETY INFORMATION FOR SOLIRIS® (eculizumab) INDICATION(S) What is SOLIRIS? SOLIRIS is a prescription medicine used to treat: people with paroxysmal nocturnal hemoglobinuria (PNH). people with atypical hemolytic uremic syndrome (aHUS). SOLIRIS is not for use in treating people with Shiga toxin E. coli related hemolytic uremic syndrome (STEC-HUS). adults with generalized myasthenia gravis (gMG) who are anti-acetylcholine receptor (AChR) antibody positive. adults with a disease called neuromyelitis optica spectrum disorder (NMOSD) who are anti-aquaporin-4 (AQP4) antibody positive. It is not known if SOLIRIS is safe and effective in children with PNH, gMG, or NMOSD. IMPORTANT SAFETY INFORMATION What is the most important information I should know about SOLIRIS? SOLIRIS is a medicine that affects your immune system and may lower the ability of your immune system to fight infections. SOLIRIS increases your chance of getting serious meningococcal infections that may quickly become life-threatening or cause death if not recognized and treated early. You must complete or update your meningococcal vaccine(s)at least 2 weeks before your first dose of SOLIRIS. If you have not been vaccinated and SOLIRIS must be started right away, you should receive the required vaccine(s) as soon as possible. If you have not been vaccinated and SOLIRIS must be started right away, you should also receive antibiotics for as long as your healthcare provider tells you. If you had a meningococcal vaccine in the past, you might need additional vaccines before starting SOLIRIS. Your healthcare provider will decide if you need additional meningococcal vaccines. Meningococcal vaccines do not prevent all meningococcal infections. Call your healthcare provider or get emergency medical care right away if you get any of these signs and symptoms of a serious meningococcal infection: fever, fever with high heart rate, headache and fever, confusion, muscle aches with flu-like symptoms, fever and rash, headache with nausea or vomiting, headache with a stiff neck or stiff back, or eyes sensitive to light. Your healthcare provider will give you a Patient Safety Card about the risk of serious meningococcal infection. Carry it with you at all times during treatment and for 3 months after your last dose of SOLIRIS. Your risk of meningococcal infection may continue for several weeks after your last dose of SOLIRIS. It is important to show this card to any healthcare provider who treats you. This will help them diagnose and treat you quickly. SOLIRIS is only available through a program called the ULTOMIRIS and SOLIRIS Risk Evaluation and Mitigation Strategy (REMS). Before you can receive SOLIRIS, your healthcare provider must: enroll in the REMS program; counsel you about the risk of serious meningococcal infections; give you information about the signs and symptoms of serious meningococcal infection; make sure that you are vaccinated against serious infections caused by meningococcal bacteria, and that you receive antibiotics if you need to start SOLIRIS right away and you are not up to date on your vaccines; give you a Patient Safety Card about your risk of meningococcal infection. SOLIRIS may also increase the risk of other types of serious infections, including Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria gonorrhoeae. Your child should receive vaccines against Streptococcus pneumoniae and Haemophilus influenzae type b (Hib) if treated with SOLIRIS. Certain people may be at risk of serious infections with gonorrhea. Certain fungal infections (Aspergillus) may occur if you take SOLIRIS and have a weak immune system or a low white blood cell count. Who should not receive SOLIRIS? Do not receive SOLIRIS if you have a serious meningococcal infection when you are starting SOLIRIS. Before you receive SOLIRIS, tell your healthcare provider about all of your medical conditions, including if you: have an infection or fever, are pregnant or plan to become pregnant, and are breastfeeding or plan to breastfeed. It is not known if SOLIRIS will harm your unborn baby or if it passes into your breast milk. Tell your healthcare provider about all the vaccines you receive and medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements which could affect your treatment. If you have PNH, your healthcare provider will need to monitor you closely for at least 8 weeks after stopping SOLIRIS. Stopping treatment with SOLIRIS may cause breakdown of your red blood cells due to PNH. Symptoms or problems that can happen due to red blood cell breakdown include: drop in the number of your red blood cell count, drop in your platelet count, confusion, kidney problems, blood clots, difficulty breathing, and chest pain. If you have aHUS, your healthcare provider will need to monitor you closely during and for at least 12 weeks after stopping SOLIRIS for signs of worsening aHUS symptoms or problems related to abnormal clotting (thrombotic microangiopathy). Symptoms or problems that can happen with abnormal clotting may include: stroke, confusion, seizure, chest pain (angina), difficulty breathing, kidney problems, swelling in arms or legs, and a drop in your platelet count. What are the possible side effects of SOLIRIS? SOLIRIS can cause serious side effects including serious infusion-related reactions. Tell your healthcare provider or nurse right away if you get any of these symptoms during your SOLIRIS infusion: chest pain, trouble breathing or shortness of breath, swelling of your face, tongue, or throat, and feel faint or pass out. If you have an infusion-related reaction to SOLIRIS, your healthcare provider may need to infuse SOLIRIS more slowly, or stop SOLIRIS. The most common side effects in people with aHUS treated with SOLIRIS include: headache, diarrhea, high blood pressure (hypertension), common cold (upper respiratory infection), stomach-area (abdominal) pain, vomiting, pain or swelling of your nose or throat (nasopharyngitis), low red blood cell count (anemia), cough, swelling of legs or feet (peripheral edema), nausea, urinary tract infections, and fever. The most common side effects in people with gMG treated with SOLIRIS include: muscle and joint (musculoskeletal) pain. The most common side effects in people with NMOSD treated with SOLIRIS include: common cold (upper respiratory infection), pain or swelling of your nose or throat (nasopharyngitis), diarrhea, back pain, dizziness, flu like symptoms (influenza) including fever, headache, tiredness, cough, sore throat, and body aches, joint pain (arthralgia), throat irritation (pharyngitis), and bruising (contusion). Tell your healthcare provider about any side effect that bothers you or that does not go away. These are not all the possible side effects of SOLIRIS. For more information, ask your healthcare provider or pharmacist. Call your healthcare provider for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. Please see the accompanying full Prescribing Information and Medication Guide for SOLIRIS, including Boxed WARNING regarding serious meningococcal infections. Notes PNH PNH is a rare, chronic, progressive and potentially life-threatening blood disorder. It is characterized by red blood cell destruction within blood vessels (also known as intravascular hemolysis) and white blood cell and platelet activation, which can result in thrombosis (blood clots).4-6 PNH is caused by an acquired genetic mutation that may happen any time after birth and results in the production of abnormal blood cells that are missing important protective blood cell surface proteins. These missing proteins enable the complement system, which is part of the immune system and is essential to the body’s defense against infection, to ‘attack’ and destroy or activate these abnormal blood cells.4 Living with PNH can be debilitating, and signs and symptoms may include blood clots, abdominal pain, difficulty swallowing, erectile dysfunction, shortness of breath, excessive fatigue, anemia and dark-colored urine.4,7,8 Clinically Significant EVH EVH, the removal of red blood cells outside of the blood vessels, can sometimes occur in PNH patients who are treated with C5 inhibitors.9,10 Since C5 inhibition enables PNH red blood cells to survive and circulate, EVH may occur when these now surviving PNH red blood cells are marked by proteins in the complement system for removal by the spleen and liver.4,6,11 PNH patients with EVH may continue to experience anemia, which can have various causes, and may require blood transfusions.9,10,12,13 A small subset of people living with PNH who are treated with a C5 inhibitor experience clinically significant EVH, which results in continued symptoms of anemia and may require blood transfusions.4,7,14,15 ALPHA ALPHA is a pivotal, global Phase III trial designed as a superiority study to evaluate the efficacy and safety of VOYDEYA as an add-on to C5 inhibitor therapy SOLIRIS or ULTOMIRIS in patients with PNH who experience clinically significant EVH. In the double-blind, placebo-controlled, multiple-dose trial, patients were enrolled and randomized to receive VOYDEYA or placebo (2:1) in addition to their ongoing SOLIRIS or ULTOMIRIS therapy for 12 weeks. A prespecified interim analysis was performed once 63 randomized patients had completed 12 weeks of the primary evaluation period or discontinued treatment as of June 28, 2022. At 12 weeks, patients on placebo plus SOLIRIS or ULTOMIRIS were switched to VOYDEYA plus SOLIRIS or ULTOMIRIS, and patients on VOYDEYA plus SOLIRIS or ULTOMIRIS remained on this treatment for an additional 12 weeks. Patients who completed both treatment periods (24 weeks) had the option to participate in a two-year long-term extension period and continue to receive VOYDEYA in addition to SOLIRIS or ULTOMIRIS. The open-label period of the study is ongoing.2,16 VOYDEYA™ (danicopan) VOYDEYA™ (danicopan) is a first-in-class oral Factor D inhibitor. The medication works by selectively inhibiting Factor D, a complement system protein that plays a key role in the amplification of the complement system response. When activated in an uncontrolled manner, the complement cascade over-responds, leading the body to attack its own healthy cells. VOYDEYA has been granted Breakthrough Therapy designation by the US Food and Drug Administration and PRIority MEdicines (PRIME) status by the European Medicines Agency. VOYDEYA has also been granted Orphan Drug Designation in the US, EU and Japan for the treatment of PNH. VOYDEYA is approved in the US as add-on therapy to ravulizumab or eculizumab for the treatment of EVH in adults with PNH. VOYDEYA is also approved in Japan for certain adults with PNH in combination with C5 inhibitor therapy. Alexion is also evaluating VOYDEYA as a potential monotherapy for geographic atrophy in a Phase II clinical trial. ULTOMIRIS® (ravulizumab-cwvz) ULTOMIRIS® (ravulizumab-cwvz), the first and only long-acting C5 complement inhibitor, provides immediate, complete and sustained complement inhibition. The medication works by inhibiting the C5 protein in the terminal complement cascade, a part of the body’s immune system. When activated in an uncontrolled manner, the complement cascade over-responds, leading the body to attack its own healthy cells. ULTOMIRIS is administered intravenously every eight weeks in adult patients, following a loading dose. ULTOMIRIS is approved in the US, EU, Japan and other countries for the treatment of certain adults with generalized myasthenia gravis (gMG). ULTOMIRIS is also approved in the US, EU, Japan and other countries for the treatment of certain adults with PNH and for certain children with PNH in the US and EU. Additionally, ULTOMIRIS is approved in the US, EU, Japan and other countries for certain adults and children with atypical hemolytic uremic syndrome to inhibit complement-mediated thrombotic microangiopathy (aHUS). Further, ULTOMIRIS is approved in the US, EU and Japan for the treatment of certain adults with neuromyelitis optica spectrum disorder (NMOSD). As part of a broad development program, ULTOMIRIS is being assessed for the treatment of additional hematology and neurology indications. SOLIRIS® (eculizumab) SOLIRIS® (eculizumab) is a first-in-class C5 complement inhibitor. The medication works by inhibiting the C5 protein in the terminal complement cascade, a part of the body’s immune system. When activated in an uncontrolled manner, the terminal complement cascade over-responds, leading the body to attack its own healthy cells. SOLIRIS is administered intravenously every two weeks, following an introductory dosing period. SOLIRIS is approved in the US, EU, Japan, China and other countries for the treatment of patients with PNH and aHUS. Additionally, SOLIRIS is approved in Japan and the EU for the treatment of certain adult and pediatric patients with gMG, and in the US, China and other countries for certain adults with gMG. Further, SOLIRIS is approved in the US, EU, Japan, China and other countries for the treatment of certain adults with NMOSD. SOLIRIS is not indicated for the treatment of patients with Shiga-toxin E. coli-related hemolytic uremic syndrome. Alexion Alexion, AstraZeneca Rare Disease, is the group within AstraZeneca focused on rare diseases, created following the 2021 acquisition of Alexion Pharmaceuticals, Inc. As a leader in rare diseases for more than 30 years, Alexion is focused on serving patients and families affected by rare diseases and devastating conditions through the discovery, development and commercialization of life-changing medicines. Alexion focuses its research efforts on novel molecules and targets in the complement cascade and its development efforts on hematology, nephrology, neurology, metabolic disorders, cardiology and ophthalmology. Headquartered in Boston, Massachusetts, Alexion has offices around the globe and serves patients in 70 countries. For more information, please visit . AstraZeneca AstraZeneca (LSE/STO/Nasdaq: AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development, and commercialization of prescription medicines in Oncology, Rare Diseases, and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. Please visit astrazeneca-us.com and follow the Company on social media @AstraZeneca. References VOYDEYA (danicopan) US prescribing information; March 2024. Lee JW, et al. Addition of danicopan to ravulizumab or eculizumab in patients with paroxysmal nocturnal haemoglobinuria and clinically significant extravascular haemolysis (ALPHA): a double-blind, randomised, phase 3 trial. The Lancet Haematology. 2023;10(12):E955-E965. Kulasekararaj AG, et al. Prevalence of clinically significant extravascular hemolysis in stable C5 inhibitor-treated patients with PNH and its association with disease control, quality of life and treatment satisfaction. Presented at: European Hematology Association (EHA) Hybrid Congress. 8-11 June 2023; Frankfurt, Germany. Abs PB2056. Brodsky RA. Paroxysmal nocturnal hemoglobinuria. Blood. 2014;124(18):2804-2811. Griffin M, et al. Significant hemolysis is not required for thrombosis in paroxysmal nocturnal hemoglobinuria. Haematologica. 2019;104(3):E94-E96. Hillmen P, et al. The complement inhibitor eculizumab in paroxysmal nocturnal hemoglobinuria. N Engl J Med. 2006;355(12):1233-1243. Kulasekararaj AG, et al. Ravulizumab (ALXN1210) vs eculizumab in C5-inhibitor-experienced adult patients with PNH: the 302 study. Blood. 2019;133(6):540–549. Hillmen P, et al. Effect of the complement inhibitor eculizumab on thromboembolism on patients with paroxysmal nocturnal hemoglobinuria. Blood. 2007;110(12):4123-4128. Brodsky RA. A complementary new drug for PNH. Blood. 2020;135(12):884–885. Risitano AM, et al. Anti-complement treatment for paroxysmal nocturnal hemoglobinuria: time for proximal complement inhibition? A position paper from the SAAWP of the EBMT. Front Immunol. 2019;10:1157. Kulasekararaj AG, et al. Long-term safety and efficacy of ravulizumab in patients with paroxysmal nocturnal hemoglobinuria: 2-year results from two pivotal phase 3 studies. Eur J Haematol. 2022;109(3):205-214. Berentsen S, et al. Novel insights into the treatment of complement-mediated hemolytic anemias. Ther Adv Hematol. 2019;10:2040620719873321. Kulasekararaj AG, et al. 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FDA feedback following the Company’s submission of a Pre-IND briefing package improves clarity on regulatory requirements for Phase 2b influenza A clinical trial with oral CC-42344, a broad-spectrum PB2 inhibitorTopline data expected in 2024 from Phase 2a influenza A human challenge study and Phase 1 study with oral CDI-988, the first potential dual coronavirus-norovirus oral antiviralInitiation of Phase 1 study expected in 2024 with inhaled CC-42344, a potential influenza treatment and post-exposure prophylactic BOTHELL, Wash., March 28, 2024 (GLOBE NEWSWIRE) -- Cocrystal Pharma, Inc. (Nasdaq: COCP) (Cocrystal or the Company) reports financial results for the 12 months ended December 31, 2023, and provides updates on its antiviral product pipeline, upcoming milestones and business activities. “We are highly encouraged by the FDA’s feedback to our Pre-Investigational New Drug (Pre-IND) package, which provides greater clarity on the regulatory requirements for a planned Phase 2b clinical trial with our novel broad-spectrum oral PB2 inhibitor CC-42344 for pandemic and seasonal influenza A,” said Sam Lee, Ph.D., President and co-CEO of Cocrystal. “This is a major step in the clinical and regulatory process for this program. We plan to file an IND for late-stage clinical development of oral CC-42344 that includes data from our ongoing Phase 2a human challenge study, which are expected later this year. “During 2024 we also expect to initiate a Phase 1 study in healthy volunteers with inhaled CC-42344 as a potential prophylactic and therapeutic for influenza A. Our inhaled formulation of CC-42344 has shown the ability to directly target influenza-infected respiratory epithelial cells in lung, allowing for higher accumulation of drug in the pulmonary system and potentially producing a rapid clinical response while reducing potential systemic side effects,” he added. “Also during the coming year we expect topline data from the ongoing first-in-human study with our pan-coronavirus and pan-norovirus oral protease inhibitor CDI-988, which is expected to serve as a Phase 1 study for both indications.” “All our programs target high-value unmet indications with novel, broad-spectrum, best-in-class antiviral candidates whose design and development uses our proprietary structure-based drug discovery platform technology,” said James Martin, CFO and co-CEO. “I’m pleased to report that under our cost-efficient business model, we believe our cash position is sufficient to fund current operations including planned clinical studies beyond the next 12 months.” Antiviral Product Pipeline Overview We are developing therapeutics that inhibit the viral replication function of RNA viruses that cause acute and chronic diseases. Our drug-discovery process focuses on the highly conserved regions of the viral enzymes and inhibitor-enzyme interactions at the atomic level. By designing and selecting antiviral drug candidates that interrupt the viral replication process and have specific binding characteristics, we seek to develop drugs that are effective against the virus and mutations of the virus, and also have reduced off-target interactions that may cause undesirable side effects. Our drug discovery process differs from traditional, empirical medicinal chemistry approaches that often require iterative high-throughput compound screening and lengthy hit-to-lead processes. Influenza ProgramsInfluenza is a severe respiratory illness that is caused by the influenza A or B virus and results in disease outbreaks mainly during the winter months. Influenza is a major global health threat that may become more challenging to treat in the future due to the emergence of highly pathogenic avian influenza viruses and resistance to approved influenza antivirals. Each year there are approximately 1 billion cases of seasonal influenza worldwide, 3-5 million severe illnesses and up to 650,000 deaths, according to the World Health Organization. On average, about 8% of the U.S. population contracts influenza each season. In addition to the health risk, influenza is responsible for approximately $10.4 billion in direct costs for hospitalizations and outpatient visits for adults in the U.S. annually. Pandemic and Seasonal Influenza A Our novel PB2 inhibitor CC-42344 has shown excellent in vitro antiviral activity against influenza A strains including pandemic and seasonal strains, as well as strains that are resistant to Tamiflu® and Xofluza®.In March 2022 we initiated enrollment in a randomized, double-blind, dose-escalating Phase 1 study to evaluate the safety, tolerability and pharmacokinetics (PK) of oral CC-42344 in healthy adults.In July 2022 we reported PK results from the single-ascending dose portion of the study that support once-daily dosing.In December 2022 we reported favorable safety and tolerability results from the oral CC-42344 Phase 1 study.In October 2023 we announced authorization from the United Kingdom Medicines and Healthcare Products Regulatory Agency to conduct a Phase 2a human challenge study.In December 2023 we began treating influenza-infected subjects in the randomized, double-blind, placebo-controlled Phase 2a human challenge study to evaluate the safety, tolerability, viral and clinical measurements of influenza A infection in subjects treated with oral CC-42344.In March 2024 we received feedback from the FDA on a Pre-IND package improving clarity on clinical trial design, drug manufacturing and nonclinical studies necessary to file a Phase 2b trial design.Preclinical development is underway with inhaled CC-42344 as a potential therapeutic and post-exposure prophylaxis for influenza A. CC-42344 has exhibited superior pulmonary exposure in preclinical testing. We expect to begin a Phase 1 clinical study with inhaled CC-42344 in Australia in 2024. Influenza A/B Program Preclinical lead optimization of replication inhibitor antiviral candidates is underway. COVID-19 and Other Coronavirus ProgramsBy targeting viral replication enzymes and protease, we believe it is possible to develop effective treatments for all diseases caused by coronaviruses including COVID-19, Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS). Our main SARS-CoV-2 protease inhibitors showed potent in vitro pan-viral activity against common human coronaviruses, rhinoviruses and respiratory enteroviruses that cause the common cold, as well as against noroviruses that can cause symptoms of acute gastroenteritis. Driven by the anticipated emergence of new COVID-19 variants, the global COVID-19 therapeutics market is estimated to exceed $16 billion by the end of 2031. Oral Protease Inhibitor CDI-988 In October 2022 we announced the selection of CDI-988 as our lead candidate for development as a potential oral treatment for SARS-CoV-2. CDI-988 exhibited superior in vitro potency against SARS-CoV-2 with activity maintained against variants of concern, and demonstrated a safety profile and PK properties that support once-daily dosing.In May 2023 we announced approval of our application to the Australian regulatory agency for a randomized, double-blind, placebo-controlled Phase 1 study to evaluate the safety, tolerability and PK of oral CDI-988 in healthy volunteers.In August 2023 we announced the selection of CDI-988 as our lead oral candidate for norovirus, in addition to coronavirus.In September 2023 we dosed the first subject in our dual norovirus-coronavirus oral CDI-988 study, which is expected to serve as a Phase 1 study for both indications.We expect topline data from the Phase 1 study with CDI-988 in 2024. Norovirus ProgramNorovirus is a highly contagious infection and is the most common cause of acute gastroenteritis, accounting for nearly one in five cases. According to the Centers for Disease Control and Prevention (CDC), an estimated 685 million cases and an estimated 200,000 deaths are attributed to norovirus each year worldwide, with an estimated societal cost of $60 billion. 3CL inhibitor CDI-988 has shown pan-viral activity against multiple norovirus strains, including the genogroup II, genotype 4 (GII.4) norovirus strain that is responsible for major norovirus outbreaks. By targeting viral replication, we believe it is possible to develop an effective treatment or short-term prophylactic for closed environments for all genogroups of norovirus. In August 2023 we announced our selection of the novel broad-spectrum oral 3CL protease inhibitor CDI-988 as our lead potential oral treatment for norovirus, in addition to coronavirus.In September 2023 we began subject dosing in a first-in-human study in healthy volunteers in Australia. The randomized, double-blind, placebo-controlled study to evaluate the safety, tolerability and PK of oral CDI-988 in healthy volunteers is expected to serve as a Phase 1 study for both indications.We expect topline data from the Phase 1 study with CDI-988 in 2024. 2023 Financial Results Research and development (R&D) expenses for 2023 were $15.2 million, compared with $12.4 million for 2022. The increase was primarily due to advancing influenza candidate CC-42344 into a Phase 2a study and advancing the dual norovirus-coronavirus candidate CDI-988 into a Phase 1 study. General and administrative (G&A) expenses for 2023 were $6.0 million, compared with $5.7 million for 2022. During 2023 the Company received $2.6 million related to litigation with an insurer, which included a $1.6 million refund from the registry of the United States Court of Appeals for the Third Circuit, reflecting the recovery of funds following a successful appeal, and $1.0 million in a settlement agreement with the insurer. Interest income for 2023 was $640,000, compared with interest expense of $2,000 for 2022. The interest income in 2023 was related to interest earned from cash held in banks and deposits with the court registry, and the interest expense in 2022 was related to finance lease agreements. The net loss for 2023 was $18.0 million, or $1.87 per share, compared with the net loss for 2022 of $38.8 million, or $4.77 per share, which included a $19.1 million non-cash impairment-loss of goodwill. Cocrystal reported unrestricted cash as of December 31, 2023 of $26.4 million, compared with $37.1 million as of December 31, 2022. Net cash used in operating activities for 2023 was $14.7 million, compared with $21.4 million for 2022. The Company had working capital of $25.0 million and 10.2 million common shares outstanding as of December 31, 2023. About Cocrystal Pharma, Inc. Cocrystal Pharma, Inc. is a clinical-stage biotechnology company discovering and developing novel antiviral therapeutics that target the replication process of influenza viruses, coronaviruses (including SARS-CoV-2), noroviruses and hepatitis C viruses. Cocrystal employs unique structure-based technologies and Nobel Prize-winning expertise to create first- and best-in-class antiviral drugs. For further information about Cocrystal, please visit www.cocrystalpharma.com. Cautionary Note Regarding Forward-Looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, including statements regarding our plans for the future development of preclinical and clinical drug candidates, our expectations regarding future characteristics of the product candidates we develop, the expected time of achieving certain value-driving milestones in our programs, including preparation, commencement and advancement of clinical studies for certain product candidates in 2024, the viability and efficacy of potential treatments for diseases our product candidates are designed to treat, expectations for the markets for certain therapeutics, our ability to execute our clinical and regulatory goals and deploy regulatory guidance towards future studies, the expected sufficiency of our cash balance to advance our programs and fund our planned operations, and our liquidity. The words "believe," "may," "estimate," "continue," "anticipate," "intend," "should," "plan," "could," "target," "potential," "is likely," "will," "expect" and similar expressions, as they relate to us, are intended to identify forward-looking statements. We have based these forward-looking statements largely on our current expectations and projections about future events. Some or all of the events anticipated by these forward-looking statements may not occur. Important factors that could cause actual results to differ from those in the forward-looking statements include, but are not limited to, the risks and uncertainties arising from the high interest rates in response to inflation, uncertainty in the financial markets, the possibility of a recession and geopolitical conflict in Ukraine and Israel on our Company, our collaboration partners, and on the U.S., UK, Australia and global economies, including manufacturing and research delays arising from raw materials and labor shortages, supply chain disruptions and other business interruptions on our ability to proceed with studies as well as similar problems with our vendors and our current and any future clinical research organization (CROs) and contract manufacturing organizations (CMOs), the ability of our CROs to recruit volunteers for, and to proceed with, clinical studies, our and our collaboration partners’ technology and software performing as expected, financial difficulties experienced by certain partners, the results of any current and future preclinical and clinical studies, general risks arising from clinical studies, receipt of regulatory approvals, regulatory changes, and potential development of effective treatments and/or vaccines by competitors, including as part of the programs financed by the U.S. government, potential mutations in a virus we are targeting that may result in variants that are resistant to a product candidate we develop. Further information on our risk factors is contained in our filings with the SEC, including our Annual Report on Form 10-K for the year ended December 31, 2023. Any forward-looking statement made by us herein speaks only as of the date on which it is made. Factors or events that could cause our actual results to differ may emerge from time to time, and it is not possible for us to predict all of them. We undertake no obligation to publicly update any forward-looking statement, whether as a result of new information, future developments or otherwise, except as may be required by law. Investor Contact:LHA Investor RelationsJody Cain310-691-7100jcain@lhai.com Media Contact:JQA PartnersJules Abraham917-885-7378Jabraham@jqapartners.com COCRYSTAL PHARMA, INC. CONSOLIDATED BALANCE SHEETS(in thousands) December 31, 2023 December 31, 2022 Assets Current assets: Cash $26,353 $37,144 Restricted cash 75 75 Tax credit receivable 890 716 Prepaid expenses and other current assets 1,773 2,243 Total current assets 29,091 40,178 Property and equipment, net 271 342 Deposits 46 46 Operating lease right-of-use assets, net (including $42 and $99 to related party) 1,851 274 Total assets $31,259 $40,840 Liabilities and stockholders’ equity Current liabilities: Accounts payable and accrued expenses $3,022 $976 Current maturities of finance lease liabilities - 7 Current maturities of operating lease liabilities (including $42 and $59 to related party) 240 233 Total current liabilities 3,262 1,216 Long-term liabilities: Operating lease liabilities (including $0 and $42 to related party) 1,613 57 Total long-term liabilities 1,613 57 Total liabilities 4,875 1,273 Commitments and contingencies Stockholders’ equity: Common stock $0.001 par value; 150,000 shares authorized as of December 31, 2023 and December 31, 2022, respectively; 10,174 and 8,143 shares issued and outstanding as of December 31, 2023 and December 31, 2022, respectively 10 8 Additional paid-in capital 342,288 337,489 Accumulated deficit (315,914) (297,930)Total stockholders’ equity 26,384 39,567 Total liabilities and stockholders’ equity $31,259 $40,840 COCRYSTAL PHARMA, INC. CONSOLIDATED STATEMENTS OF OPERATIONS(unaudited)(in thousands, except per share data) December 31, 2023 2022 Operating expenses: Research and development $15,169 $12,392 General and administrative 5,990 5,745 Legal settlement (2,600) 1,600 Impairments - 19,092 Total operating expenses 18,559 38,829 Loss from operations (18,559) (38,829) Other (expense) income: Interest income (expense), net 640 (2)Change in fair value of derivative liabilities - 12 Foreign exchange loss (65) (18)Total other income (expense), net 575 (8) Net loss $(17,984) $(38,837) Net loss per common share: Loss per share, basic and diluted $(1.87) $(4.77)Weighted average number of common shares outstanding, basic and diluted 9,651 8,143 # # #