ABCA1

Seven years into its existence, Character Biosciences is ready to enter the clinic with a pair of experimental medicines targeting a bustling area of ophthalmology. The New Jersey biotech aims to treat age-related macular degeneration, a key driver of blindness in older adults, based on insights from genetic and imaging data that it collected from more than 6,500 people in an observational study. To get its first candidates into Phase 1 this year, Character announced Tuesday that it raised a $93 million Series B. The biotech previously raised $28 million in funding, including an $18 million Series A in 2022. The financing should take the 30-employee startup through Phase 2 testing for both intravitreal drug candidates, CEO and co-founder Cheng Zhang told Endpoints News . Investors are aMoon, Luma Group, Bausch + Lomb, Jefferson Life Sciences (an affiliate of Jefferson River Capital), Innovation Endeavors, Catalio Capital Management, S32 and KdT Ventures. Character is the second private biotech to announce a funding round on Tuesday after Hillstar Bio revealed its $67 million debut . It’s rare right now to see more than one venture funding round announcement per day, according to a Stifel report on Sunday. The average number of biotech venture rounds per month has slid 10% from two years ago and cratered 40% from the vibrant market of four years ago, according to the Stifel bankers. Character chose its drug targets based on the patient data from the observational study, and the startup believes that wealth of data can also give it a better shot at clinical success because it can hone in on the patients most likely to respond to treatment. Plus, the company worked with more than 150 ophthalmology centers for the observational study, and it plans to use some of those sites for upcoming clinical trials. “It’s been a long journey. It’s taken seven years, in fact, but we didn’t want to make any shortcuts,” Zhang said. “We wanted to build a rigorous company that is rooted in the fundamental science of patient data.” The company is exploring CTX114 as a treatment to slow the progression of geographic atrophy in advanced dry AMD, an increasingly popular category for drugmakers. Astellas and Apellis Pharmaceuticals both received FDA approval for geographic atrophy therapies in 2023 but have since faced regulatory setbacks. Last year, Astellas withdrew its application in Europe, and Apellis’ treatment was rebuffed by the bloc’s regulators, who raised questions about clinical benefit and safety. Like Astellas’ Izervay and Apellis’ Syfovre, Character is also pursuing the complement pathway with CTX114 but is tackling a “different genetically supported” part, according to Zhang. CTX114 is an engineered version of FHL-1, or factor H-like protein 1, a negative regulator of complement activation. Izervay is a complement 5 inhibitor and Syfovre is a C3 inhibitor. The company hopes CTX114 can also offer a less-frequent dosing schedule than Izervay and Syfovre, which are dosed monthy and every 25 to 60 days, respectively. As part of its due diligence on Character, aMoon investors talked with practicing ophthalmologists about the GA landscape, including Izervay and Syfovre. “They said, ‘Look, the risk-benefit for both of these drugs is just not amazing,'” aMoon partner Reut Shema said in an interview. “They said, ‘But we have nothing else. So if you give me something that’s similar efficacy, but just a little bit safer, it’s a multibillion-dollar drug.'” Meanwhile, with CTX203, Character hopes to thwart a patient’s progression to advanced AMD. CTX203 is an apolipoprotein A1 mimetic peptide that aims to stabilize ABCA1 expression. Character is also working with Bausch + Lomb to create new medicines for AMD. The duo began collaborating early last year and announced that work in January. Financial terms have’t been disclosed. “We would love, at a certain time, to move from incidence-driven drug development into a population-specific drug development,” Bausch + Lomb chief medical officer Yehia Hashad said in an interview. Character wants its platform to decipher which patients will be responders from the outset — before even going into clinical studies. “The more we are able to predict patients and treat them prior to getting to the late-stage part of the disease, the better,” Hashad said. The Bausch + Lomb tie-up does not involve Character’s CTX114 or CTX203. “Those could be highly competitive assets,” aMoon’s Shema said, “and because there’s so much interest from pharma companies, we wanted to make sure that this was open territory for different pharmas to bid for those because we think both of them have potential to be multibillion-dollar drugs.” Shema pointed out that Character also has datasets in glaucoma, which could form the basis for additional partnerships.

Character Biosciences, a biotechnology startup developing treatments for vision loss, said Tuesday it raised $93 million in a Series B round.The financing will help Character bring its two most advanced programs into clinical testing. One, dubbed CTX114, is being tested in geographic atrophy, a common eye condition and an advanced stage of age-related macular degeneration, or AMD. The other, CTX203, is designed to halt progression in people with intermediate AMD, so they dont develop geographic atrophy or other forms of advanced disease. Both drug prospects should begin Phase 1 trials this year.In geographic atrophy, Character aims to challenge two marketed drugs Apellis Pharmaceuticals Syfovre and Astellas Pharmas Izervay. Both can slow the growth of the patchy, map-like eye lesions that create blind spots in people with geographic atrophy. However, testing hasnt clearly shown that doing so preserves vision. And in rare cases, Syfovre has been associated with severe side effects.Like Syfovre and Izervay, CTX114 works on the complement system, an arm of the bodys immune system. According to Character co-founder and CEO Cheng Zhang, CTX114 does so differently, mimicking the function of a protein that stops the complement system from overactivating, but that malfunctions in AMD. Preclinical testing has suggested the approach may be more effective, though that hasnt been proven in humans.Characters second drug is being developed for people who dont yet have advanced AMD and arent typically treated. CTX203 is designed to stabilize expression of a protein called ABCA1 thats involved in lipid transport by retinal cells. Lower ABCA1 levels are associated with an abnormal buildup of lipids that can lead to AMD progression.While there are many medications for wet AMD, drugmakers have had less success with the dry form that accounts for the bulk of the estimated 200 million people worldwide with the disease. Zhang says a big reason why is the diseases heterogeneity and varied progression, which makes it difficult to design clinical trials. Character has collected a trove of AMD patient data to help design its drugs and identify the specific groups of people it intends to enroll in studies.What gives us comfort is that we have mapped out those challenges, we have a deeper understanding of how we might mitigate those risks, Zhang said. We can subtype patients, understand those patients who are more likely to respond to our therapy, and have a drug that has more applications in the first place.Characters Series B round was led by aMoon and Luma Group, and involved Bausch + Lomb, Jefferson Life Sciences and four other investors. Bausch + Lomb also announced a collaboration with the biotech in January.Characters patient-first approach is unique in its ability to identify those who are most likely to benefit from therapy, and we look forward to seeing the clinical impact of this approach with the use of proceeds from this financing, Jamie Kasuboski, a partner and head of research at Luma Group, said in a statement.Character was formerly known as Clover Therapeutics, which was launched in 2019 by the health insurance firm Clover Health. The company previously raised an $28 million in funding, Zhang said. '

LA JOLLA, Calif., May 28, 2024 (GLOBE NEWSWIRE) -- MediciNova, Inc., a biopharmaceutical company traded on the NASDAQ Global Market (NASDAQ: MNOV) and the Standard Market of the Tokyo Stock Exchange (Code Number: 4875), today announced that MediciNova conducted two poster presentations at the 92nd European Atherosclerosis Society (EAS) 2024 Congress held online May 26-29, 2024. MediciNova’s Chief Medical Officer, Kazuko Matsuda, MD PhD MPH presented an update on the Company’s “STUDY PROTOCOL TO EVALUATE MN-001’S (TIPELUKAST) EFFICACY, SAFETY AND TOLERABILITY IN SUBJECTS WITH NON-ALCOHOLIC FATTY LIVER DISEASE (NAFLD) (Abstract # 810) “, which included Clinical background, Study objectives, Study design, Inclusion Criteria and Study status of Phase 2 clinical trial ongoing in the US. As of 25 April 2024, 33 patients were enrolled, 19 patients were randomized, 14 patients completed the study. Three subjects reported serious adverse events (SAE) and were all considered “Unlikely related” or “Unrelated“ to study drug. MediciNova’s Dr. Huicheng Qi presented “MN-002, THE METABOLITE OF MN-001 (TIPELUKAST) PROMOTES MACROPHAGE CHOLESTEROL EFFLUX (Abstract # 856)”, demonstrating positive data regarding cholesterol efflux capacity by MN-001 (Tipelukast) and MN-002. This is a collaborative effort between MediciNova and Professor Masatsune Ogura at Department of Clinical Laboratory Technology, Juntendo University and Professor Takashi Miida at Department of Clinical Laboratory Medicine, Juntendo University. Objectives of this study are to evaluate the effects of MN-001 and its major active metabolite MN-002 on cholesterol efflux capacity in THP-1 *1macrophages. ABCA1 *2 and ABCG1 *3 is known to play important roles in the reverse cholesterol transport system. Macrophages derived from THP-1 *3 cells were used to analyze the effect of MN-001 and MN-002 on ABCA1 and ABCG1 mRNA expression was measured by RT-PCR and protein expression was measured by Western blotting. Next, the effects of MN-002 on Apolipoprotein AI (ApoA1) *4 dependent and High-Density Lipoprotein (HDL) dependent cholesterol efflux in THP-1 macrophages were determined, respectively. Finally, analyzed the involvement of Protein Kinase A (PKA) in the mechanism of action of MN-002 using a PKA inhibitor. The data presented in the abstract demonstrated the following: MN-002 enhances ApoA1 and HDL mediated cholesterol efflux. MN-002 increased 44.3% in ApoA1-mediated cholesterol efflux capacity compared to the control group (DMSO). MN-002 increased 15.3% in HDL-mediated cholesterol efflux capacity compared to the control group (DMSO). MN-002 increases ABCA1 and ABCG1 protein levels in dose-dependent manner MN-002 increased ABCA1 protein expression in a dose-dependent manner compared to the control group (DMSO); ABCA1 protein increased approximately 2-fold with 10 µM of MN-002. MN-002 increased ABCG1 protein expression in a dose-dependent manner compared to the control group (DMSO); ABCG1 protein increased approximately 2.8-fold with 10 µM of MN-002. MN-002 increases ABCA1/ ABCG1/ LXR-alpha mRNA levels. MN-002 increased ABCA1 mRNA expression in a time and dose-dependent manner compared to the control group (DMSO). mRNA expression of ABCA1 increased about 3-fold with 24 hours exposure of 10 µM MN-002. MN-002 increased ABCG1 mRNA expression in a time and dose-dependent manner compared to the control group (DMSO). mRNA expression of ABCA1 by increased 5.4-fold with 24 hours exposure of 10 µM MN-002 MN-002 increased LXR-alpha mRNA expression in a time- and dose-dependent manner compared to the control group (DMSO). mRNA expression of ABCA1 increased 2.4-fold with 24 hours exposure of 10 µM MN-002. MN-002 increases ABCA1 protein level independent of PKA signaling pathway. MN-002 increased ABCA1 protein expression compared to the control group (DMSO); conditions in which a PKA inhibitor did not cancel the effect of MN-002 to increase ABCA1 protein expression. Kazuko Matsuda, M.D., Ph.D., M.P.H., Chief Medical Officer, MediciNova, Inc., commented, “We are very pleased to present our clinical trial status and positive research outcomes at the EAS Congress 2024. We have randomized almost half of the randomization goal with our ongoing Phase 2 clinical trial. With the collaborative research with Juntendo University regarding the mechanism of action of MN-001/MN-002 in lipid metabolism, we identified that MN-002, the major metabolite of MN-001 (Tipelukast), had significant positive effects on both ABCA1, ABCG1 expression.” *1 About THP-1 THP-1 is a human leukemia monocytic cell line, which has been extensively used to study monocyte/macrophage functions, mechanisms, signaling pathways, and nutrient and drug transport. *2 About ABCA1: ATP-binding cassette transporter ABCA1 (member 1 of human transporter sub-family ABCA), also known as the cholesterol efflux regulatory protein (CERP) is a protein which in humans is encoded by the ABCA1 gene. This transporter is a major regulator of cellular cholesterol and phospholipid homeostasis. ABCA1 is an integral cell membrane protein that protects against cardiovascular disease. *3 About ABCG1 The primary function of ATP-binding cassette transporter G1 (ABCG1) is to efflux cholesterol to spherical high-density lipoproteins (HDL). ABCG1 also effluxes cholesterol to low-density lipoproteins (LDL), liposomes and cyclodextrin and it exports sphingomyelin, phosphatidylcholine and oxysterols to HDL and albumin. *4 About Apolipoprotein AI (ApoA1) Apolipoprotein A-I (Apo A-I) is a major protein that has specific roles in the lipid metabolism. It promotes cholesterol efflux by accepting fats from cells to the liver for excretion. AboutNAFLD,Type2DiabetesMellitus(T2DM),andHypertriglyceridemia NAFLD is considered the hepatic manifestation of metabolic syndrome; studies have reported that 50% of patients with metabolic syndrome also have NAFLD. There is sufficient clinical and epidemiological evidence supporting the assertion that NAFLD is strongly associated with an increased prevalence and incidence of cardiovascular disease, T2DM, chronic kidney disease, and malignancy. The presence of dyslipidemia (hypercholesterolemia, hypertriglyceridemia, or both) is reported in 20 - 80% of NAFLD cases. AboutMN-001 MN-001 (tipelukast) is a novel, orally bioavailable, small molecule compound thought to exert its effects through several mechanisms to produce its anti-inflammatory and anti-fibrotic activity in preclinical models, including leukotriene (LT) receptor antagonism, inhibition of phosphodiesterases (PDE) (mainly 3 and 4), and inhibition of 5-lipoxygenase (5-LO). The 5-LO/LT pathway has been postulated as a pathogenic factor in fibrosis development, and MN-001's inhibitory effect on 5-LO and the 5-LO/LT pathway is a novel approach to treat fibrosis. MN-001 has been shown to down-regulate expression of genes that promote fibrosis including LOXL2, Collagen Type 1 and TIMP-1. MN-001 has also been shown to down-regulate expression of genes that promote inflammation including CCR2 and MCP-1. In addition, MN-001 was found to inhibit triglyceride synthesis in hepatocytes by inhibiting arachidonic acid uptake. About MediciNova MediciNova, Inc. is a clinical-stage biopharmaceutical company developing a broad late-stage pipeline of novel small molecule therapies for inflammatory, fibrotic, and neurodegenerative diseases. Based on two compounds, MN-166 (ibudilast) and MN-001 (tipelukast), with multiple mechanisms of action and strong safety pro MediciNova has 11 programs in clinical development. MediciNova’s lead asset, MN-166 (ibudilast), is currently in Phase 3 for amyotrophic lateral sclerosis (ALS) and degenerative cervical myelopathy (DCM) and is Phase 3-ready for progressive multiple sclerosis (MS). MN-166 (ibudilast) is also being evaluated in Phase 2 trials in Long COVID and substance dependence. MN 001 (tipelukast) was evaluated in a Phase 2 trial in idiopathic pulmonary fibrosis (IPF) and a second Phase 2 trial in non-alcoholic fatty liver disease (NAFLD) is ongoing. MediciNova has a strong track record of securing investigator-sponsored clinical trials funded through government grants. Statements in this press release that are not historical in nature constitute forward-looking statements within the meaning of the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. These forward-looking statements include, without limitation, statements regarding the future development and efficacy of MN-166, MN-001, MN-221, and MN-029. These forward-looking statements may be preceded by, followed by, or otherwise include the words "believes," "expects," "anticipates," "intends," "estimates," "projects," "can," "could," "may," "will," "would," “considering,” “planning” or similar expressions. These forward-looking statements involve a number of risks and uncertainties that may cause actual results or events to differ materially from those expressed or implied by such forward-looking statements. Factors that may cause actual results or events to differ materially from those expressed or implied by these forward-looking statements include, but are not limited to, risks of obtaining future partner or grant funding for development of MN-166, MN-001, MN-221, and MN-029 and risks of raising sufficient capital when needed to fund MediciNova's operations and contribution to clinical development, risks and uncertainties inherent in clinical trials, including the potential cost, expected timing and risks associated with clinical trials designed to meet FDA guidance and the viability of further development considering these factors, product development and commercialization risks, the uncertainty of whether the results of clinical trials will be predictive of results in later stages of product development, the risk of delays or failure to obtain or maintain regulatory approval, risks associated with the reliance on third parties to sponsor and fund clinical trials, risks regarding intellectual property rights in product candidates and the ability to defend and enforce such intellectual property rights, the risk of failure of the third parties upon whom MediciNova relies to conduct its clinical trials and manufacture its product candidates to perform as expected, the risk of increased cost and delays due to delays in the commencement, enrollment, completion or analysis of clinical trials or significant issues regarding the adequacy of clinical trial designs or the execution of clinical trials, and the timing of expected filings with the regulatory authorities, MediciNova's collaborations with third parties, the availability of funds to complete product development plans and MediciNova's ability to obtain third party funding for programs and raise sufficient capital when needed, and the other risks and uncertainties described in MediciNova's filings with the Securities and Exchange Commission, including its annual report on Form 10-K for the year ended December 31, 2023 and its subsequent periodic reports on Form 10-Q and current reports on Form 8-K. Undue reliance should not be placed on these forward-looking statements, which speak only as of the date hereof. MediciNova disclaims any intent or obligation to revise or update these forward-looking statements. INVESTOR CONTACT: David H. Crean, Ph.D. Chief Business Officer MediciNova, Inc info@medicinova.com