TGF-β1 x PDL1

Preclinical data from the next generation eyedrop platform to be unveiled for the first time at ARVO 2024 DAEJEON, South Korea, April 22, 2024 /PRNewswire/ -- PharmAbcine, Inc. ("PharmAbcine" or the "Company") (KOSDAQ: 208340), a clinical-stage public company developing next generation therapeutics to treat medical unmet needs, announced today that the Company's U.S. subsidiary, Wincal Biopharm, Inc. ("WincalBio"), will present preclinical findings on its innovative ocular drug delivery platform at the upcoming conference, Association for Research in Vision and Ophthalmology (ARVO), the world's largest ophthalmology conference which will be held from May 5th to 9th, 2024 in Seattle, WA, United States. Based in South San Francisco, California, WincalBio is an emerging biotech dedicated to developing next-generation ocular drug delivery platforms and therapeutics for vascular diseases. Its proprietary Ocular Penetration Carrier (OPC) screening platform has shown high potential in treating various ocular diseases using eyedrop formulation of antibody therapeutics, thereby replacing the need for intravitreal injections. This novel OPC platform has a mechanism in facilitating the delivery of antibody therapeutics through the vitreous humor of the eye, reaching critical structures such as the aqueous chamber, vitreous, retina, and choroid. WincalBio stands as a pioneer in biotech industry with a leading program validated in mouse CNV models for anti-VEGF antibody therapies, a significant advancement in treating age-related macular degeneration (AMD) and diabetic macular edema (DME). These breakthroughs, along with preclinical data from various animal models, will be unveiled for the first time at ARVO 2024. While anti-VEGF antibody therapies are the standard of care for AMD treatment, they are currently limited to intravitreal injections. Dr. TaeWeon Lee, Chief Scientific Officer of WincalBio, underscored the importance of presenting these groundbreaking findings at ARVO, noting, "The OPC platform, developed internally over the past few years, has never been publicly disclosed. Presenting the preclinical data for the first time at ARVO holds tremendous significance." Additionally, Dr. Venice Chiueh, Director at WincalBio and the oral presenter, expressed gratitude for the keen interest of ARVO meeting organizers. "We appreciate the opportunity provided by ARVO reviewers to present advancements in eyedrop development. We are committed to ensuring the success of clinical studies aimed at transitioning existing patients from intravitreal injections to eyedrop applications." Eyedrop applications of therapeutics offer significant advantage of being non-invasive, as well as enhancing patient convenience with minimum side effects. While effectively delivering sufficient quantities of the therapeutics to the back of the eye remains the primary challenge for topical applications, WincalBio's OPC platform aims to overcome this challenge. ARVO, founded in 1928, is the world's largest ophthalmology conference with over 10,000 members from over 75 countries. The schedule of the presentation is as follows: Presentation Number: 2159 Presentation Title: Development of eyedrops for anti-VEGF therapeutic antibodies as a substitute for IVT injection for posterior ocular disease indications Session Number: 240 Session Title: Advancements in age-related macular degeneration: Novel drugs, delivery systems, and mechanistic insights Session Date/Start Time: May 6, 2024 from 3:00 PM to 3:15 PM Room: Yakima 1 (Seattle Convention Center - Arch Building) About Wincal Biopharm, Inc. Wincal Biopharm (WincalBio) is focused on developing vascular therapeutics. Our current focus is on developing eyedrop formulations for therapeutic antibodies using proprietary Ocular Penetration Carrier (OPC) screening platform to identify a matching antibody:carrier pair that allows therapeutic antibodies reach intraocular space including aqueous chamber, vitreous, retina and choroid, which is difficult without injection. This non-invasive eyedrop delivery of therapeutic antibodies without intravitreal injections opens up broader treatment opportunities for multiple intraocular diseases including wet AMD, DME, diabetic retinopathy, uveitis, geographic atrophy, thyroid eye disease and uveal melanoma to lower the treatment burden for both patients and clinicians. It can be used as a monotherapy with already FDA approved anti-VEGF antibodies as well as combination with other novel target antibodies including cytokine targets such as ILs (IL-1, IL-4, IL-6, IL-10, IL-17, IL-18, IL-23), TNFa, TGFb, FGF, PDGF, FasL, EGFR as well as ocular cancer targets (PD-1, PD-L1, CTLA4). Currently, anti-VEGF antibody is a lead program with preclinical efficacy demonstration in mouse CNV model, and planning to do clinical studies in 2026 followed by other novel target antibody programs and combination programs. At WincalBio, our commitment to in vivo science with a needle free drug delivery underpins to improve patient's quality of life and compliance. About OPC Platform Ocular Penetration Carrier (OPC) platform is an in vivo ocular penetration screening to quickly identify a matching cargo protein to carrier formulation from our proprietary carrier library. Delivered target protein localization from cornea, anterior chamber, vitreous, retina, choroid and optic nerve can be monitored with a labeled fluorescent signal. A wide variety of large molecule therapeutic candidates including Fab, scFv, IgGs, Fc fusion proteins, recombinant proteins and growth factors can be delivered to the back of eye. Our proprietary carriers were designed to facilitate large molecules to intraocular target area. About Aflibercept-ED (WBP-101) Aflibercept-ED (WBP-101) is an aflibercept/OPC eyedrop formulation to target retinal area without using needles. Aflibercept has been clinically well proven anti-VEGF therapeutics with the delivery route of intravitreal injections. WBP-101 eyedrop application can significantly improve ease of use and avoid injection related issues including pain, bleeding, infection or inflammation and may improve patient adherence rate by lowering treatment related burdens. Patients can easily apply eyedrops at home, which can replace IVT injection procedures for ocular disease treatment. WBP-101 can be a primary monotherapy or can be used as a maintenance therapy after an initial IVT injection. Combination therapy is also possible by delivering different pathway blocking antibodies in a single formulation. Preclinical PoC in mouse CNV model demonstrated a comparable efficacy profile to the IVT injected. For additional information about Wincal Biopharm, Inc., visit . SOURCE PharmAbcine

Study published in NAR Cancer, a leading peer-reviewed journal in the field of nucleic acid therapeutics HONG KONG, Germantown, Md. and SUZHOU, China, Jan. 24, 2024 /PRNewswire/ -- Sirnaomics Ltd. (the "Company", Stock Code: 2257, together with its subsidiaries, the "Group" or "Sirnaomics"), a leading biopharmaceutical company engaging in discovery and development of advanced RNAi therapeutics, announced today the Company published a research article with NAR Cancer. The article reveals a novel mechanism of action of lead RNAi cancer drug candidate, STP707, a polypeptide nanoparticle (PNP) formulation comprised of two active siRNA (small interfering RNA) inhibitors targeting TGF-β1 and COX-2 for intravenous treatment of solid tumors. The publication provides support to the company's ongoing clinical studies and a strong rationale for combination treatment with immune-checkpoint inhibitors. The published study, 'Codelivery of TGFβ and Cox2 siRNA inhibits HCC by promoting T-cell penetration into the tumor and improves response to Immune Checkpoint Inhibitors' demonstrates how PNP delivered the siRNA to multiple cell types besides hepatocytes in the liver. It also demonstrates that STP707 can simultaneously deliver the siRNAs targeting TGF-β1 and COX-2 to tumor cells. Systemic administration of the PNP packaged with dual-targeted siRNAs (2mg/kg) in mice bearing orthotopic hepatocellular carcinoma (HCC) tumors induced tumor growth inhibition to an undetectable level. A combination study with a lower dosage of the siRNAs (1mg/kg) and PD-L1 mAbs revealed an additive effect on tumor growth inhibition and an increase in penetration of CD4+ and CD8+ T-cells into the tumor microenvironment. These study results provide a scientific rationale for further exploration using STP707 for the treatment of HCC and potentially other solid tumors. "By publishing Sirnaomics' pioneering efforts in cancer RNAi therapeutics with the leading peer-reviewed journal in the field of nucleic acid therapeutics, it demonstrates strong scientific rationale for developing STP707," said Dr. Patrick Lu, Founder, Chairman of the Board, Executive Director, President and Chief Executive Officer of Sirnaomics. "The newly described mechanism of action of dual-targets TGF-β1 and COX-2 siRNAs for enhancing antitumor immunogenicity provides further scientific foundation for recent successes from our Phase I clinical study for STP707, as a single drug and, potentially, in combination with immune check point inhibitors." The corresponding author of the publication, Dr. David Evans, Executive Director and Head of Discovery of Sirnaomics, commented, "The discovery from this study illustrates for the first time that silencing both TGF-β1 and COX-2 simultaneously in the tumor microenvironment may enhance antitumor activity through recruitment of activated CD4+ and CD8+ T-cells. Tumor inhibition is further augmented when an immune checkpoint inhibitor is added to STP707." About Sirnaomics (stock code: 2257) Sirnaomics is an RNA therapeutics biopharmaceutical company that focuses on the discovery and development of innovative drugs for indications with unmet medical needs and large market opportunities. Sirnaomics is the first clinical-stage RNA therapeutics company to have a strong presence in both Asia and the United States. Based on its proprietary delivery technologies, a polypeptide nanoparticle RNAi platform and GalNAc RNAi platform, GalAhead™, Sirnaomics has established an enriched drug candidate pipeline. STP122G, which represents the first drug candidate utilizing the Company's GalAhead™ technology, is currently in Phase I development. The Company has also had multiple successes with oncology applications through its clinical programs for STP705 and STP707. With the establishment of the it manufacturing facility in China, Sirnaomics is undergoing a transition from a biotech company to a biopharma corporation. Learn more at: . SOURCE Sirnaomics

-Reduced TGF-β2, but not TGF-β1 nor TGF-β3, is associated with improved OS. AGOURA HILLS, Calif., Dec. 19, 2022 (GLOBE NEWSWIRE) -- Oncotelic Therapeutics, Inc (OTCQB:OTLC) ("Oncotelic", the "Company" or "We"), a clinical stage biotechnology company, today announced today announced it presented new clinical confirming TGF-β2 as the appropriate target for gliomas at the 12th AACR-JCA Joint Conference: Breakthroughs in Cancer Research— Translating Knowledge into Practice December 10 - 14, 2022, Maui, Hawaii. TGF- β consists of three highly similar isoforms: β1, β2, β3Retrospective analysis TCGA database demonstrated that high TGF-β2, but not TGF-β1 nor TGF-β3, is prognostic indicator for worse OS.Reduced TGF-β2 in Pediatric Brainstem Patients increased OS from 9 mos to 22 mos, N=95 pts, p<0.0001.Reduced TGF-β2 in Gliomas patients treated with TMZ increased OS from 25 mos to 94 mos, N=230 pts, p<0.0001.Reduced TGF-β2 in Gliomas patients treated with Radiation increased OS from 25 mos to 94 mos, N=293 pts, p<0.0001. The presentation is now available on our website (www.oncotelic.com). Abstract # B22. OT-101 for DMG “The immunosuppressive growth factor, TGF-β, plays a major role in formation of desmoplasia and promoting tumor growth and metastasis. However, the recent failure of bintrafusp alfa, a bifunctional fusion protein immunotherapy combined a TGF-β1 trap with the anti-PD-L1, which GlaxoSmithKline acquired for 4.2B, casted doubt on the field. The new data presented at JCA confirmed our commitment to TGF-β2 and explained the spectacular failure of the bintrafusp alfa” said Dr. Vuong Trieu, CEO and Chairman of Oncotelic. About Oncotelic Oncotelic (f/k/a Mateon Therapeutics, Inc.), was formed in the State of New York in 1988 as OXiGENE, Inc., was reincorporated in the State of Delaware in 1992, and changed its name to Mateon Therapeutics, Inc. in 2016, and Oncotelic Therapeutics, Inc. in November 2020. Oncotelic is seeking to leverage its deep expertise in oncology drug development to improve treatment outcomes and survival of cancer patients with a special emphasis on rare pediatric cancers. Oncotelic has rare pediatric designation for Diffuse Intrinsic Pontine Glioma “DIPG” (through OT-101) through its 45% joint venture, melanoma (through CA4P), and Acute Myeloid Leukemia “AML” (through OXi 4503). Oncotelic also acquired PointR Data Inc. in November 2019. Oncotelic acquired AL-101, during the 4th quarter of 2021, for the intranasal delivery of apomorphine. We intend to develop AL-101 for the treatment of Parkinson Disease ("PD"). Over 60,000 new patients are being diagnosed with PD in the United States and currently there are over 1 million patients in the US and expected to increase to over 1.2 million by 2030. In addition, approximately 10 million suffer from this disease globally. https://www.parkinson.org/Understanding-Parkinsons/Statistics. AL-101 is also being developed for Erectile Dysfunction ("ED"). ED is the most prevalent male sexual disorder globally. The percentages of men affected by ED are as follows: 14.3-70% of men aged 60 years, 6.7-48% of men aged 70 years, and 38% of men aged 80 years (Geerkens MJM et al. (2019). Eur Urol Focus. pii: S2405-4569(19)30079-3). However, with the increasing administration of PDE5 inhibitors in clinical practice, it was found that approximately 30-35% of ED patients are treatment failures (McMahon CN et al. (2006). BMJ, 332: 589-92). AL-101 is designed to target treatment failure ED patients who do not respond to PDE5 inhibitors. Through similar mechanism of action, AL-101 is being developed for Female Sexual Dysfunction ("FSD"). Female sexual dysfunction is a prevalent problem, afflicting approximately 40% of women and there are few treatment options. FSD is more typical as women age and is a progressive and widespread condition. (Allahdadi, KJ et al. (2009) Cardiovascular & hematological agents in medicinal chemistry, 7(4), 260-269). There is no available drug for the treatment of FSD. In June 2019, the U.S. Food and Drug Administration approved Vyleesi (bremelanotide) to treat acquired, generalized hypoactive sexual desire disorder ("HSDD") in premenopausal women. This is the only available drug treatment. Vyleesi has essentially replaced the only other drug for HSDD - however, it has a long list of drug-drug interactions, including commonly used antidepressants, such as fluoxetine and sertraline. In addition, it has a black box warning regarding its use with alcohol, a combination that has been associated with hypotension and syncopal episodes. Therefore, there is an urgent need for effective therapy against FSD and HSDD. About OT-101 Oncotelic jointly owns OT-101 with its joint venture partners Dragon and GMP Bio. OT-101 has completed seven clinical trials including one phase 2 trial in COVID and two phase 2 trials in brain cancer and against pancreatic cancer. It has pediatric designation for a rare form of pediatric brain cancer known as DIPG. There are about 200-300 new cases of DIPG every year in the United States. DIPG most often occurs in children aged 5-10 years old. Treatment options are limited with surgery being contraindicated. Most children do not survive more than 2 years after diagnosis. Currently, the main treatment for DIPG is radiation therapy. Although radiation temporarily improves symptoms in most patients, it is not a cure. Palliative care or quality of life services help patients and families manage pain and other symptoms, promote quality of life, and making difficult decisions including treatment choices and end of life care. When COVID-19 emerged in China, Oncotelic and GMP entered into a research and services agreement in February 2020 to develop and test COVID-19 antisense therapeutics. In March 2020, Oncotelic reported the anti-viral activity of OT-101. The anti-viral activity of OT-101, in an in vitro antiviral testing performed by an independent laboratory, OT-101 has a 50% effective concentration (EC50) of 7.6 µg/mL and is not toxic at the highest dose of 1000 µg/mL giving a safety index (SI) value of >130, which is considered highly active and on par or superior to Remdesivir - a Gilead drug. Unlike Remdesivir, OT-101 targets not only the virus replication but also the virus induced pneumonia and fibrosis. Our Phase 2 trial was completed for OT-101 in South America. This was a randomized, double-blind, placebo-controlled Phase 2 study intended to evaluate the safety and efficacy of OT-101 in adult patients hospitalized with positive SARS-CoV-2 and pneumonia. As reported in November 2021, the top line data was positive for safety and efficacy. For more information, please visit www.oncotelic.com Oncotelic's Cautionary Note on Forward-Looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements, other than statements of historical facts, included in this communication regarding strategy, future operations, future financial position, prospects, plans and objectives of management are forward-looking statements. Words such as "may", "expect", "anticipate" "hope", "vision", "optimism", "design", "exciting", "promising", "will", "conviction", "estimate," "intend," "believe", "quest for a cure of cancer", "innovation-driven", "paradigm-shift", "high scientific merit", "impact potential" and similar expressions are intended to identify forward-looking statements. Forward looking statements contained in this press release include, but are not limited to, statements about future plans related to the operations of the JV, taking the JV into an initial public offering or the success thereof, the progress, timing of clinical development, scope and success of future clinical trials, the reporting of clinical data for the company's product candidates and the potential use of the company's product candidates to treat various cancer indications as well as obtaining required regulatory approval to conduct clinical trials and upon granting of approval by the regulatory agencies, the successful marketing of the products. Each of these forward-looking statements involves risks and uncertainties, and actual results may differ materially from these forward-looking statements or may not occur at all. Many factors may cause differences between current expectations and actual results, including unexpected safety or efficacy data observed during preclinical or clinical studies, clinical trial site activation or enrollment rates that are lower than expected, changes in expected or existing competition, changes in the regulatory environment, failure of collaborators to support or advance collaborations or product candidates and unexpected litigation or other disputes, taking the Company or its affiliates through initial public offerings. These risks are not exhaustive, the company faces known and unknown risks, including the risk factors described in the Company's annual report on Form 10-K filed with the SEC on April 15, 2022 and in the company's other periodic filings. Forward-looking statements are based on expectations and assumptions as of the date of this press release. Except as required by law, the company does not assume any obligation to update forward-looking statements contained herein to reflect any change in expectations, whether as a result of new information, future events, or otherwise. Contact Information: For Oncotelic Therapeutics, Inc.: Investor Relations ir@oncotelic.com