Anti-Inflammatory Effects and Photo- and Neuro-Protective Properties of BIO203, a New Amide Conjugate of Norbixin, in Development for the Treatment of Age-Related Macular Degeneration (AMD).

Article

作者: Dinan, Laurence ; Lafont, René ; Clatot, Justine ; Guibout, Louis ; Dilda, Pierre J ; Fournié, Mylène ; Balducci, Christine ; Camelo, Serge ; Boumedine, Thinhinane ; Fontaine, Valérie ; Sahel, José-Alain ; Nguyen, Vincent ; Monteiro, Elodie ; Veillet, Stanislas ; Latil, Mathilde

9'-cis-norbixin (norbixin/BIO201) protects RPE cells against phototoxicity induced by blue light and N-retinylidene-N-retinylethanolamine (A2E) in vitro and preserves visual functions in animal models of age-related macular degeneration (AMD) in vivo. The purpose of this study was to examine the mode of action and the in vitro and in vivo effects of BIO203, a novel norbixin amide conjugate. Compared to norbixin, BIO203 displays improved stability at all temperatures tested for up to 18 months. In vitro, BIO203 and norbixin share a similar mode of action involving the inhibition of PPARs, NF-κB, and AP-1 transactivations. The two compounds also reduce IL-6, IL-8, and VEGF expression induced by A2E. In vivo, ocular maximal concentration and BIO203 plasma exposure are increased compared to those of norbixin. Moreover, BIO203 administered systemically protects visual functions and retinal structure in albino rats subjected to blue-light illumination and in the retinal degeneration model of Abca4^-/- Rdh8^-/- double knock-out mice following 6 months of oral complementation. In conclusion, we report here that BIO203 and norbixin share similar modes of action and protective effects in vitro and in vivo. BIO203, with its improved pharmacokinetic and stability properties, could be developed for the treatment of retinal degenerative diseases such as AMD.

PloS one3区 · 综合性期刊

Norbixin Protects Retinal Pigmented Epithelium Cells and Photoreceptors against A2E-Mediated Phototoxicity In Vitro and In Vivo

3区 · 综合性期刊

ArticleOA

作者: Brazhnikova, Elena ; Lesage, Laëtitia ; Fontaine, Valérie ; Feraille, Laurence ; Monteiro, Elodie ; Guibout, Louis ; Sahel, José-Alain ; Veillet, Stanislas ; Lafont, René ; Elena, Pierre-Paul ; Balducci, Christine

The accumulation of N-retinylidene-N-retinylethanolamine (A2E, a toxic by-product of the visual pigment cycle) in the retinal pigment epithelium (RPE) is a major cause of visual impairment in the elderly. Photooxidation of A2E results in retinal pigment epithelium degeneration followed by that of associated photoreceptors. Present treatments rely on nutrient supplementation with antioxidants. 9'-cis-Norbixin (a natural diapocarotenoid, 97% purity) was prepared from Bixa orellana seeds. It was first evaluated in primary cultures of porcine retinal pigment epithelium cells challenged with A2E and illuminated with blue light, and it provided an improved photo-protection as compared with lutein or zeaxanthin. In Abca4-/- Rdh8-/- mice (a model of dry AMD), intravitreally-injected norbixin maintained the electroretinogram and protected photoreceptors against light damage. In a standard rat blue-light model of photodamage, norbixin was at least equally as active as phenyl-N-tert-butylnitrone, a free radical spin-trap. Chronic experiments performed with Abca4-/- Rdh8-/- mice treated orally for 3 months with norbixin showed a reduced A2E accumulation in the retina. Norbixin appears promising for developing an oral treatment of macular degeneration. A drug candidate (BIO201) with 9'-cis-norbixin as the active principle ingredient is under development, and its potential will be assessed in a forthcoming clinical trial.

项与 Macuneos 相关的新闻（医药）

2021-07-12

·GlobeNewswire

Biophytis Presents Positive Preclinical Data on Sarconeos (BIO101) in COVID-19 at ECCMID 2021

PARIS and CAMBRIDGE, Mass., July 12, 2021 (GLOBE NEWSWIRE) -- Biophytis SA (Nasdaq CM: BPTS, Euronext Growth Paris: ALBPS), (“Biophytis” or the “company”), a clinical-stage biotechnology company focused on the development of therapeutics that are aimed at slowing the degenerative processes associated with aging and improving functional outcomes for patients suffering from age-related diseases, including severe respiratory failure in patients suffering from COVID-19 today announces new positive preclinical data on Sarconeos (BIO101) in hamsters infected with SARS-CoV-2. The data will be presented as an ePoster at the 31st European Congress of Clinical Microbiology & Infectious Diseases (ECCMID), which will take place online from 9-12 July 2021. This study reveals that Sarconeos (BIO101) daily treatment prevents respiratory function deterioration in SARS-CoV-2-infected mammals and provides a solid preclinical proof of concept for the ongoing Phase 2-3 COVA clinical study. Stanislas Veillet, President and CEO of Biophytis, said: “These preclinical data are further evidence of the potential of Sarconeos (BIO101) to be an effective treatment for patients with COVID-19. We are continuing our COVA Phase 2-3 study with Sarconeos (BIO101) in patients infected with COVID-19 and are looking forward to results of the second interim analysis in Q3 2021. We are prepared to rapidly scale up capacity, should we receive regulatory approval for Sarconeos (BIO101) in COVID-19, having secured contracts with a major global Custom Development and Manufacturing Organization (CDMO) for the manufacturing of registration batches.” In the study, hamsters were inoculated intranasally with 106 TCID50/mL. Sarconeos (BIO101) was administered daily at 10 mg/kg*day. Three groups of 6-7-week-old female hamsters were compared: uninfected hamsters treated with the vehicle (control; n=10), SARS-CoV-2-infected hamsters treated with the vehicle (n=10), and SARS-CoV-2-infected hamster treated with BIO101 (n=10). Pulmonary function was assessed by whole-body plethysmography. The results showed that at 5 dpi, the Penh value, a classical measure of respiratory distress proven to be relevant in corona virus airway infections, was significantly increased in the group of SARS-CoV-2-infected hamsters treated with the vehicle, compared to the uninfected control group (0.63 ± 0.11 versus 0.28 ± 0.01, p<0.01). In animals treated with Sarconeos (BIO101), the Penh value was significantly reduced compared to vehicle-treated infected animals (0.35 ± 0.02, p<0.05). Inspiration (66.4 ± 2.6 msec) and expiration (134.9 ± 3.2 msec) times in Sarconeos (BIO101)-treated animals were significantly lower than in the vehicle-treated group of infected hamsters (88.4 ± 6.87 msec, p<0.01; 150.7 ± 5.2 msec, p<0.05, respectively). End Expiratory Pause (EEP) is proportional to the degree of obstruction of the lower airways. In Sarconeos (BIO101)-treated animals, EEP time was significantly lower compared to infected animals treated with the vehicle (12.6 ± 0.3 vs 18.8 ± 1.6 msec, p<0.01). The daily administration of BIO101 for 5 days remarkably restored the EEP time of the treated animals (CI 95%: 11.9-13.4), to a comparable level of uninfected control animals (CI 95%: 11.3-13.4). About BIOPHYTISBiophytis SA is a clinical-stage biotechnology company specialized in the development of therapeutics that are aimed at slowing the degenerative processes associated with aging and improving functional outcomes for patients suffering from age-related diseases, including severe respiratory failure in patients suffering from COVID-19. Sarconeos (BIO101), our leading drug candidate, is a small molecule, administered orally, being developed as a treatment for sarcopenia in a Phase 2 clinical trial in the United States and Europe (SARA-INT). It is also being studied in a clinical two-part Phase 2-3 study (COVA) for the treatment of severe respiratory manifestations of COVID-19 in Europe, Latin America, and the US. A pediatric formulation of Sarconeos (BIO101) is being developed for the treatment of Duchenne Muscular Dystrophy (DMD). The company is based in Paris, France, and Cambridge, Massachusetts. The company's common shares are listed on Euronext Growth (Ticker: ALBPS -ISIN: FR0012816825) and ADSs are listed on Nasdaq Capital Market (Ticker BPTS – ISIN: US09076G1040). For more information visit DisclaimerThis press release contains forward-looking statements. Forward-looking statements include all statements that are not historical facts. In some cases, you can identify these forward-looking statements by the use of words such as "outlook," "believes," "expects," "potential," "continues," "may," "will," "should," "could," "seeks," "predicts," "intends," "trends," "plans," "estimates," "anticipates" or the negative version of these words or other comparable words. These forward-looking statements include statements regarding Biophytis’ anticipated timing for its various Sarconeos (BIO101) clinical trials and expectations regarding commercialization. Such forward-looking statements are based on assumptions that Biophytis considers to be reasonable. However, there can be no assurance that the statements contained in such forward-looking statements will be verified, which are subject to various risks and uncertainties including, without limitation, delays in patient recruitment or retention, interruptions in sourcing or supply chain, its ability to obtain the necessary regulatory authorizations, COVID-19-related delays, and the impact of the current pandemic on the Company’s clinical trials. The forward-looking statements contained in this press release are also subject to risks not yet known to Biophytis or not currently considered material by Biophytis. Accordingly, there are or will be important factors that could cause actual outcomes or results to differ materially from those indicated in these statements. Please refer to the "Risk Factors" section of the Company's Annual 2020 Report available on BIOPHYTIS website () and to the risks discussed in the Company’s registration statement on Form F-1 and other reports filed with the Securities and Exchange Commission (the “SEC”). We undertake no obligation to publicly update or review any forward-looking statement, whether as a result of new information, future developments or otherwise, except as required by law. Biophytis Contact for Investor RelationsEvelyne Nguyen, CFO E : evelyne.nguyen@biophytis.com Media contactLife Sci Advisors Sophie Baumont/Chris MaggosE: sophie@lifesciadvisors.comT: +33 6 27 74 74 49

合作抗体小分子药物

2021-04-29

·GlobeNewswire

Biophytis Receives €980,000 DeepTech Funding from BPI

PARIS and CAMBRIDGE, Mass., April 29, 2021 (GLOBE NEWSWIRE) -- Biophytis SA (Euronext Growth Paris: ALBPS), a clinical-stage biotechnology company focused on the development of therapeutics aimed at slowing the degenerative processes associated with aging and improving functional outcomes for patients suffering from age-related diseases, including severe respiratory failure in patients suffering from COVID-19, today announces it was granted a non-dilutive funding of €980,000 from the public investment bank BPI France’s DeepTech program, for its MACA program of Macuneos (BIO201) in dry Age-Related Macular Degeneration (AMD). The DeepTech program aims to boost highly innovative and breakthrough projects emerging from fundamental research with attractive dedicated financing tools. The funding consists of a conditional advance of €600,000 and a grant of €380,000 which will complement existing financing for preclinical studies of Biophytis’ MACA clinical program in treatment of dry AMD, an age-related degeneration of the macula, the central part of the retina. AMD is one of the leading causes of irreversible vision loss and blindness in people over the age of 50. Stanislas Veillet, President and CEO of Biophytis, said: “We are pleased with this funding award, which recognizes the potential of Biophytis’ Macuneos (BIO201), which has demonstrated promising results in preclinical studies. There is still no available treatment for dry AMD and the loss of vision has a significant impact on patients’ quality of life. Macuneos (BIO201) has the potential to address a major unmet medical need and we look forward to further investigating it in clinical phases.” Biophytis plans to initiate a Phase 1 clinical trial (MACA-PK) in healthy volunteers in the second half of 2021, subject to regulatory review and approval as well as COVID-19-related delays and the impact of the pandemic on operational capabilities. Macuneos (BIO201) is an orally administered small molecule in development for the treatment of diseases of the retina, or retinopathies. It is a plant-derived pharmaceutical-grade purified 9 cis-norbixin, or norbixin. Biophytis has completed preclinical cellular and animal studies of Macuneos (BIO201) for the treatment of retinopathies. Biophytis believes that the results from preclinical studies support continued investigation to whether Macuneos (BIO201) may stimulate biological resilience and protect the retina against phototoxic damage that leads to vision loss. Dry AMD is a common eye disorder among people over the age of 50 that affects central vision, impairing functions such as reading, driving, and facial recognition, and has a major impact on quality of life and the ability to live independently. There are currently no approved drugs for dry AMD. Based on estimates from publicly available information, AMD affects approximately 8.5% of the global population (ages 45 to 85) and is expected to increase over time as the population ages. About BIOPHYTIS Biophytis SA is a clinical-stage biotechnology company specialized in the development of therapeutics that are aimed at slowing the degenerative processes associated with aging and improving functional outcomes for patients suffering from age-related diseases, including severe respiratory failure in patients suffering from COVID-19. Sarconeos (BIO101), our leading drug candidate, is a small molecule, administered orally, being developed as a treatment for sarcopenia in a Phase 2 clinical trial in the United States and Europe (SARA-INT). It is also being studied in a clinical two-part Phase 2-3 study (COVA) for the treatment of severe respiratory manifestations of COVID-19 in Europe, Latin America, and the US. A pediatric formulation of Sarconeos (BIO101) is being developed for the treatment of Duchenne Muscular Dystrophy (DMD). The company is based in Paris, France, and Cambridge, Massachusetts. The company's common shares are listed on Euronext Growth (Ticker: ALBPS -ISIN: FR0012816825) and ADSs are listed on Nasdaq Capital Market (Ticker BPTS – ISIN: US09076G1040). For more information visit DisclaimerThis press release contains forward-looking statements. Forward-looking statements include all statements that are not historical facts. In some cases, you can identify these forward-looking statements by the use of words such as "outlook," "believes," "expects," "potential," "continues," "may," "will," "should," "could," "seeks," "predicts," "intends," "trends," "plans," "estimates," "anticipates" or the negative version of these words or other comparable words. These forward-looking statements include statements regarding Biophytis’ anticipated timing for its Interim Analysis of Part 1 and release of full study results. Such forward-looking statements are based on assumptions that Biophytis considers to be reasonable. However, there can be no assurance that the statements contained in such forward-looking statements will be verified, which are subject to various risks and uncertainties including, without limitation, delays in patient recruitment or retention, interruptions in sourcing or supply chain, its ability to obtain the necessary regulatory authorizations, COVID-19-related delays, and the impact of the current pandemic on the Company’s clinical trials. The forward-looking statements contained in this press release are also subject to risks not yet known to Biophytis or not currently considered material by Biophytis. Accordingly, there are or will be important factors that could cause actual outcomes or results to differ materially from those indicated in these statements. In France, please also refer to the "Risk Factors" section of the Company's Annual 2019 Report and the Company’s Half Year 2020 Report available on BIOPHYTIS website (). We undertake no obligation to publicly update or review any forward-looking statement, whether as a result of new information, future developments or otherwise, except as required by law. Biophytis Contact for Investor RelationsEvelyne Nguyen, CFO evelyne.nguyen@biophytis.com Media contactLife Sci Advisors Sophie Baumont/Chris MaggosE: sophie@lifesciadvisors.comT: +33 6 27 74 74 49 Investor RelationsLifeSci Advisors, LLC Ligia Vela-ReidE: lvela-reid@lifesciadvisors.com

合作小分子药物

2021-04-29

·BioSpace

Biophytis Receives €980,000 DeepTech Funding from BPI France for the development of Macuneos (BIO201) in Dry AMD

DeepTech funding supports advanced and highly differentiating biotech projects with significant commercial potential Biophytis plans to initiate Phase 1 clinical trial in the second half of 2021 PARIS and CAMBRIDGE, Mass., April 29, 2021 (GLOBE NEWSWIRE) -- Biophytis SA (Euronext Growth Paris: ALBPS), a clinical-stage biotechnology company focused on the development of therapeutics aimed at slowing the degenerative processes associated with aging and improving functional outcomes for patients suffering from age-related diseases, including severe respiratory failure in patients suffering from COVID-19, today announces it was granted a non-dilutive funding of €980,000 from the public investment bank BPI France’s DeepTech program, for its MACA program of Macuneos (BIO201) in dry Age-Related Macular Degeneration (AMD). The DeepTech program aims to boost highly innovative and breakthrough projects emerging from fundamental research with attractive dedicated financing tools. The funding consists of a conditional advance of €600,000 and a grant of €380,000 which will complement existing financing for preclinical studies of Biophytis’ MACA clinical program in treatment of dry AMD, an age-related degeneration of the macula, the central part of the retina. AMD is one of the leading causes of irreversible vision loss and blindness in people over the age of 50. Stanislas Veillet, President and CEO of Biophytis, said: “We are pleased with this funding award, which recognizes the potential of Biophytis’ Macuneos (BIO201), which has demonstrated promising results in preclinical studies. There is still no available treatment for dry AMD and the loss of vision has a significant impact on patients’ quality of life. Macuneos (BIO201) has the potential to address a major unmet medical need and we look forward to further investigating it in clinical phases.” Biophytis plans to initiate a Phase 1 clinical trial (MACA-PK) in healthy volunteers in the second half of 2021, subject to regulatory review and approval as well as COVID-19-related delays and the impact of the pandemic on operational capabilities. Macuneos (BIO201) is an orally administered small molecule in development for the treatment of diseases of the retina, or retinopathies. It is a plant-derived pharmaceutical-grade purified 9 cis-norbixin, or norbixin. Biophytis has completed preclinical cellular and animal studies of Macuneos (BIO201) for the treatment of retinopathies. Biophytis believes that the results from preclinical studies support continued investigation to whether Macuneos (BIO201) may stimulate biological resilience and protect the retina against phototoxic damage that leads to vision loss. Dry AMD is a common eye disorder among people over the age of 50 that affects central vision, impairing functions such as reading, driving, and facial recognition, and has a major impact on quality of life and the ability to live independently. There are currently no approved drugs for dry AMD. Based on estimates from publicly available information, AMD affects approximately 8.5% of the global population (ages 45 to 85) and is expected to increase over time as the population ages. About BIOPHYTIS Biophytis SA is a clinical-stage biotechnology company specialized in the development of therapeutics that are aimed at slowing the degenerative processes associated with aging and improving functional outcomes for patients suffering from age-related diseases, including severe respiratory failure in patients suffering from COVID-19. Sarconeos (BIO101), our leading drug candidate, is a small molecule, administered orally, being developed as a treatment for sarcopenia in a Phase 2 clinical trial in the United States and Europe (SARA-INT). It is also being studied in a clinical two-part Phase 2-3 study (COVA) for the treatment of severe respiratory manifestations of COVID-19 in Europe, Latin America, and the US. A pediatric formulation of Sarconeos (BIO101) is being developed for the treatment of Duchenne Muscular Dystrophy (DMD). The company is based in Paris, France, and Cambridge, Massachusetts. The company's common shares are listed on Euronext Growth (Ticker: ALBPS -ISIN: FR0012816825) and ADSs are listed on Nasdaq Capital Market (Ticker BPTS – ISIN: US09076G1040). For more information visit Disclaimer This press release contains forward-looking statements. Forward-looking statements include all statements that are not historical facts. In some cases, you can identify these forward-looking statements by the use of words such as "outlook," "believes," "expects," "potential," "continues," "may," "will," "should," "could," "seeks," "predicts," "intends," "trends," "plans," "estimates," "anticipates" or the negative version of these words or other comparable words. These forward-looking statements include statements regarding Biophytis’ anticipated timing for its Interim Analysis of Part 1 and release of full study results. Such forward-looking statements are based on assumptions that Biophytis considers to be reasonable. However, there can be no assurance that the statements contained in such forward-looking statements will be verified, which are subject to various risks and uncertainties including, without limitation, delays in patient recruitment or retention, interruptions in sourcing or supply chain, its ability to obtain the necessary regulatory authorizations, COVID-19-related delays, and the impact of the current pandemic on the Company’s clinical trials. The forward-looking statements contained in this press release are also subject to risks not yet known to Biophytis or not currently considered material by Biophytis. Accordingly, there are or will be important factors that could cause actual outcomes or results to differ materially from those indicated in these statements. In France, please also refer to the "Risk Factors" section of the Company's Annual 2019 Report and the Company’s Half Year 2020 Report available on BIOPHYTIS website (). We undertake no obligation to publicly update or review any forward-looking statement, whether as a result of new information, future developments or otherwise, except as required by law. Biophytis Contact for Investor Relations Evelyne Nguyen, CFO evelyne.nguyen@biophytis.com Media contact Life Sci Advisors Sophie Baumont/Chris Maggos E: sophie@lifesciadvisors.com T: +33 6 27 74 74 49 Investor Relations LifeSci Advisors, LLC Ligia Vela-Reid E: lvela-reid@lifesciadvisors.com

合作小分子药物

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