MMP9

VYN201 demonstrated positive effect on key biomarkers relevant to vitiligo Data supports VYN201’s rapid onset of action and previously announced positive clinical results Program is on track for Phase 2b initiation in Q2 Jan. 10, 2024 (GLOBE NEWSWIRE) -- VYNE Therapeutics Inc. (Nasdaq: VYNE) (“VYNE” or the “Company”), a clinical-stage biopharmaceutical company developing proprietary, innovative and differentiated therapies for the treatment of immuno-inflammatory conditions, today announced new biomarker data from the previously completed Phase 1b trial in patients with nonsegmental vitiligo. The data show that BET inhibitor, VYN201, had a positive effect on multiple disease-associated biomarkers. Positive clinical data from the Phase 1b trial were announced in October 2023. The trial was a 16-week open-label study assessing the safety, tolerability, pharmacokinetics, and exploratory efficacy of once-daily topical VYN201 in 29 patients with a clinical diagnosis of active nonsegmental vitiligo, in three dose cohorts (0.5%, 1.0% and 2.0% strengths). Enrolled subjects had two, non-facial active vitiligo lesions. One lesion, selected for treatment with VYN201, had skin tissue biopsies taken prior to first application of VYN201 and after 8 weeks of treatment. Biopsies were analyzed to quantify the effect of VYN201 on specific biomarkers related to inflammation associated with vitiligo, melanocyte proliferation, and melanogenesis. Exploratory data from the 1.0% and 2.0% cohorts showed that VYN201 treatment demonstrated biological activity and a positive effect on certain key biomarkers relevant to vitiligo disease severity and progression. The magnitude of biomarker modulation was more pronounced in the 2.0% dose cohort than in the 1.0% dose cohort, indicative of an emerging dose-response. Results from the biomarker analyses include the following: Downregulation of Matrix metalloproteinase-9 (MMP-9) levels: VYN201 induced the downregulation of MMP-9 in biopsied lesional skin after 8 weeks of treatment compared to baseline. MMP-9 is an inflammatory biomarker associated with the detachment and subsequent loss of melanocytes from skin in vitiligo and is elevated in patients with vitiligo. At Week 8, there was a median reduction in MMP-9 of 40.8% in lesional skin compared to baseline for subjects in the 2.0% cohort. Upregulation of melanocyte-related transcription factors (MRTFs): VYN201 induced the upregulation of multiple MRTFs, including SRY-box transcription factor 10 (SOX10), Lymphoid-enhancing factor-1 (LEF1), β-Catenin and Microphthalmia associated transcription factor (MITF), after 8 weeks of treatment compared to baseline. Each of these markers are linked to the proliferation of melanocytes, recovery in melanogenesis, and subsequent re-pigmentation of skin. In the 2.0% cohort, SOX10, LEF1, β-Catenin and MITF transcription factors had median increases of 36.1%, 90.2%, 16.5% and 15.2% in their respective expression levels in lesional skin compared to baseline. “VYN201’s potential to reduce melanocyte detachment by downregulating MMP-9 and by upregulating the expression of proteins relevant to melanocyte proliferation and melanogenesis is promising, and I look forward to the continued advancement of VYN201 as a potential differentiated therapy for vitiligo,” said Amit Pandya, M.D., former President of the Global Vitiligo Foundation and Dermatologist, Department of Dermatology, Palo Alto Foundation Medical Group. “We are encouraged by these new biomarker data from the Phase 1b trial for VYN201, building on our recently announced positive clinical results,” said David Domzalski, President and CEO of VYNE. “We’ve made considerable progress in advancing this program, and we look forward to initiating a Phase 2b trial evaluating VYN201 in patients with both active and stable nonsegmental vitiligo in the second quarter of this year.” The loss of functional melanocytes in vitiligo is associated with the generation of inflammatory mediators that facilitate melanocyte detachment in skin.1 This cellular detachment occurs due to the disrupted surface distribution of adhesion molecule E-cadherin and the release of soluble E-cadherin.2 E-cadherin cleavage may be induced by several metalloproteinases including MMP-9. MMP-9 is secreted by the keratinocytes in response to various proinflammatory cytokines such as IFN-γ and TNF-α.3 The Wnt/β-catenin pathway plays an essential role in pigmentation by regulating both melanocyte differentiation and melanogenesis through the action of MITF.4 β-catenin is increased by the binding of Wnt proteins to their receptors, leading to transport of β-catenin into the nucleus, where it regulates transcription of MITF through interactions with several transcription factors that include LEF1 and SOX10. MITF also regulates transcription of downstream genes key for melanin synthesis and melanocyte cell development. Vitiligo is a chronic autoimmune depigmenting disorder of the skin, characterized by the loss of pigment producing cells known as melanocytes. Vitiligo is the most common depigmenting skin condition, with a prevalence estimated at 0.5-2.0% of the world population.5 There is currently only one FDA-approved product for the treatment of vitiligo. Nonsegmental vitiligo is the most common type of vitiligo. VYN201 is a pan-bromodomain BET inhibitor designed to be locally-administered as a “soft” drug to address diseases involving multiple, diverse inflammatory cell signaling pathways while providing low systemic exposure. To date, VYN201 has produced consistent reductions in pro-inflammatory and disease-related biomarkers and improvements in disease severity, and demonstrated local activity in several preclinical models (using several different routes of administration). BET proteins play a key role in regulating gene transcription via epigenetic interactions (“reading”), and recent research has determined a key role for these proteins in regulating B cell and T cell activation and subsequent inflammatory processes. As epigenetic readers, BET proteins regulate the recruitment of transcriptional factors that are key to the production of several pro-inflammatory cytokines. BET inhibitors have the potential to treat a range of immuno-inflammatory and fibrotic diseases by blocking pro-inflammatory cytokine transcription with additional potential in myeloproliferative neoplastic disorders. 1. Picardo, M. et al. Nat. Rev. Dis. Primer 1, 15011 (2015). 2. Delmas, V. & Larue, L. Exp. Dermatol. 28, 662–666 (2019). 3. Boukhedouni, N. et al. JCI Insight 5, 133772 (2020). 4. Zhao SJ et al, Clin Cosmet Investig Dermatol. Sep 1;14:1089-11031 (2021). 5. Rosmarin et al, Lancet (2020);396:110-120. VYNE’s mission is to improve the lives of patients by developing proprietary, innovative and differentiated therapies for the treatment of immuno-inflammatory conditions. The Company’s unique and proprietary bromodomain & extra-terminal (BET) domain inhibitors, which comprise its InhiBET™ platform, include a locally administered pan-BD BET inhibitor (VYN201) and an orally available BD2-selective BET inhibitor (VYN202) that were licensed from Tay Therapeutics Limited. 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Leading Diagnostic Healthcare Company Highlights Value Proposition of Expanding IP Portfolio Which Includes 13 Different Filings and Allowances SAN DIEGO--(BUSINESS WIRE)-- Axim Biotech, Inc. (OTCQB: AXIM) (“AXIM Biotech,” “AXIM” or “the Company”), an international healthcare diagnostic solutions development company, announced today the receipt of notification by the United States Patent & Trademark Office of several patent allowances. AXIM has been developing a proprietary diagnostic platform that can be adapted to test for a variety of analytes including, for example, SARS-Cov-2, Lactoferrin, IgE, Lacritin, MMP-9. This innovative platform allows clinicians to detect with greater speed and accuracy different conditions that, e.g., allow for point of care testing of viruses, diseases, and conditions such as Dry Eye Disease. The platform capability can also be applied to rapid testing for vaccine candidates, including COVID vaccines and a potential Fentanyl vaccine. AXIM’s proprietary platform can also be used to enable point-of-care detection for one or more cancers using a unique cancer biomarker, QSOX1-L. The first patent application recently allowed relates to COVID and other neutralizing antibody (Nab) testing and treatment. The allowance confirms that AXIM was a pioneer in developing a rapid point of care Nab test and its novelty. Additionally, the company was notified by the USPTO of a second patent allowance for systems and methods for rapid diagnostic for various cancers. The invention relates to the discovery by AXIM scientists of a unique biomarker for cancer, QSOX1-L. A third patent allowance was received for a point-of-care apparatus and methods for detecting cancer that uniquely uses electrochemical or impedance spectroscopy (EIS). These allowances have increased the depth of AXIM’S IP portfolio to include 13 patent applications, including the above allowed applications, that cover AXIM’s innovative platforms and technologies. The Company see’s significant value in its IP portfolio whereas it may look to either further develop the covered technologies or license the IP to larger healthcare organizations, both creating significant upside value of the organization. “These allowances further validate both the novelty and underlaying science of our diagnostic technologies,” said John Huemoeller II, CEO of AXIM Biotechnologies. “While we continue to manufacture and ship our FDA-cleared diagnostic assays to customers through our commercialization partner, we have simultaneously continued to expand our value proposition through innovations in diagnostics field, that are now protected under the USPTO. We see our growing IP portfolio as a major opportunity for the organization, with an unrealized market value which probably exceeds the company’s current market capitalization. For instance, while the original SAR COVID-19 virus which plagued the world in recent years received extensive attention from the medical community, our now protected assay methodology can be applied to any future mutations or new SARS viruses or vaccines.” Below is an overview of AXIM’s patent portfolio: SARS-Cov-2. Neutralizing Antibody Testing and Treatment. 1 Allowed Patent; 3 Utility Patent Applications. The invention is a diagnostic test intended for semi-quantitative measurement of neutralizing antibodies in plasma, serum or whole blood of persons who have had recent or prior infection with SARS-CoV2 or have received a COVID-19 vaccine. DRY EYE DISEASE 1. Tests for Human Monomeric Lacritin. 1 Utility Patent Application The invention relates to a Rapid Point of Care test for Human Monomeric Lacritin. Lacritin is a tear protein that, in its monomeric form, autonomously promotes tearing and ocular surface survival. Lower concentrations of Lacritin may diagnose several eye diseases, including Blepharitis, Sjögren’s syndrome, Dry Eye Disease and other inflammatory conditions. 2. Tear Sample Collectors Systems and Methods. 1 Utility Patent Application Tear fluid analysis contributes to the greater understanding of various ocular and systemic diseases and obtaining adequate samples for tear analysis requires effective collection methods. Most tear sample collectors on the market use capillary designs that are intimidating to the patient. The invention relates to a laminated and looped tear sample collector that is cost-effective, easy to use and soft and non-intimidating to the user and patient. 3. Use of Micromesh Materials in Diagnostic Devices. 1 Provisional Patent Application When small sample sizes (0.1-2 microliters) are used, such as tears, there is a need for the sample to be spread out over application area for a proper flow. The invention allows dispersion of a small sample volume into mesh cells over a wide area controllable by the mesh size. This enables homogeneous sample dispersion over the entire sample application area. CANCER DIAGNOSTICS Systems and Methods for Rapid Diagnostic for Various Cancers. 1 Allowed Patent Application QSOX1-L, a splice variant of QSOX1, has been identified as a novel biomarker of bladder cancer and possibly other cancers in serum. Proprietary antibodies have been generated that selectively detect only this variant and not others. QSOX1-L has been used to develop a rapid and cost-effective diagnostic test for bladder and possibly other urologic cancers from urine. PLATFORM TECHNOLOGY Molecules and Related Assays, Test Kits and Methods. 1 Utility Patent Application, 1 Provisional Patent Application. The invention relates to the use of various recombinant proteins, test kits, test kit components and methods for detecting and measuring “binding antibodies” (for example, non-neutralizing antibodies) as well as “functional antibodies” (for example, neutralizing) in a single test and at the same time. Such test kit and method can advantageously improve the diagnosis and therapy of various diseases. NEW DIAGNOSTIC TEST Fentanyl Diagnostic Test. 1 Provisional Patent Application Researches have reported that broadly neutralizing antibodies may prevent lethality from the fentanyl class of synthetic opioids. The University of Houston is developing a vaccine targeting the dangerous synthetic opioid fentanyl that could block its ability to enter the brain. The invention relates to a test that can measure neutralizing antibodies against fentanyl, either therapeutic or generated by anti-fentanyl vaccine. The test can be used to monitor the vaccine’s response and help decide when a booster is needed. NEW TECHNOLOGY Point of Care Apparatus and Methods for Detecting Cancer Using Electrochemical Impedance or Capacitance Spectroscopy 1 allowed patent. 1 Allowed Patent, 1 Utility Patent Application The presence of cancer biomarkers or other analytes can be detected in the bodily fluid using EIS or ECS in devices, such as handheld point-of-care devices. The devices, as well as systems and methods, utilize using EIS or ECS in combination with an antibody or other target-capturing molecule on a working electrode. Imaginary impedance or phase shift, as well as background subtraction, also may be utilized. About AXIM® Biotechnologies Founded in 2014, AXIM® Biotechnologies, Inc. (AXIM) is a vertically integrated research and development company focused on improving the landscape for the diagnosis of ophthalmological conditions such as Dry Eye Disease (DED) through rapid diagnostic tests. The Company owns two of the only five FDA Cleared Diagnostic tests for Dye Eye Disease. For more information, please visit . Forward-Looking Statements The statements made by Axim Biotechnologies Inc., in this press release may be “forward-looking” in nature within the meaning of Section 27A of the Securities Act of 1933, Section 21E of the Securities Exchange Act of 1934 and the Private Securities Litigation Reform Act of 1995. Forward-looking statements describe Axim’s future plans, projections, strategies and expectations, and are based on assumptions and involve a number of risks and uncertainties, many of which are beyond the control of Axim Biotechnologies, Inc. Actual results could differ materially from those projected due to there being no assurance that our diagnostic candidate will ever be approved for use by the U.S. FDA or any equivalent foreign regulatory agency. Further, Axim’s eye care diagnostic products that are FDA cleared may not be manufactured in large enough quantities or that third parties with established eye care physicians will enter into agreements or purchase from the Company, and even if the Company’s diagnostic candidates are successful, they may generate only limited revenue and profits for the Company. Various other factors are detailed from time to time in Axim’s SEC reports and filings, including our Annual Report on Form 10-K filed on April 15, 2023, and other reports we the SEC, which are available at . Axim Biotechnologies, Inc., undertakes no obligation to update publicly any forward-looking statements to reflect new information, events or circumstances after the date hereof or to reflect the occurrence of unanticipated events, unless otherwise required by law.

CAMBRIDGE, Mass., June 9, 2023 /PRNewswire/ -- Sumitomo Pharma Oncology, Inc., a clinical-stage company focused on novel cancer therapeutics, today presented updated preliminary data from the ongoing Phase 1/2 study evaluating TP-3654, an investigational selective oral PIM1 kinase inhibitor, in patients with myelofibrosis (MF) previously treated with or ineligible for JAK inhibitor therapy. Initial preliminary data was presented at American Society of Hematology (ASH) Annual Meeting & Exposition 2022. Updated results were presented in a poster presentation at the European Hematology Association (EHA) 2023 Hybrid Congress, being held June 8-11, 2023 in Frankfurt, Germany as well as virtually on the Congress platform from June 8-11, 2023. Preliminary data of TP-3654 monotherapy in relapsed/refractory myelofibrosis (MF) patients showed spleen volume reduction (SVR), and total symptom score (TSS) improvement.1 Further, TP-3654 may prompt early cytokine changes that may correlate with symptoms response. "We are encouraged by these preliminary clinical data and are pleased that in dose ranges evaluated to date, TP-3654 has been well-tolerated with no myelosuppressive treatment-related adverse events (TRAEs). Our commitment remains to continue to advance this program with additional clinical sites and contributing to the progress of potential treatment options, which may improve outcomes for patients with myelofibrosis," said Patricia S. Andrews, Chief Executive Officer and Global Head of Oncology, Sumitomo Pharma Oncology, Inc. As of February 9, 2023, 15 patients were enrolled across 5 dose levels from 480mg QD to 720 mg BID. The results showed SVR observed in 7 of 10 evaluable patients treated for ≥ 12 weeks. TSS improvements were observed in 9 of 10 evaluable patients. Broad reductions in cytokines were observed after TP-3654 treatment. At week 12 analysis, patients with higher cytokine reductions correlated with higher TSS improvement. BM fibrosis reduction from grade 3 to 2 was seen in one patient who also achieved spleen and symptoms responses and showed reductions in MF associated cytokines: IL6 (68%), IL12p40 (83%), MMP9 (56%), and EN-RAGE (68%), and is on active treatment for more than 18 months.1 Overall, TP-3654 appears to be well tolerated with no dose limiting toxicity (DLT) observed to date. The most common adverse events are Grade 1 and 2 diarrhea, nausea, and vomiting.1 "These updated preliminary data of oral TP-3654 as a monotherapy in patients with MF presented at EHA 2023 are encouraging as we evaluate the pharmacodynamic markers changes in MF patients treated with TP-3654," said Jatin J. Shah, M.D., Chief Medical Officer and Global Head of Development, Sumitomo Pharma Oncology (SMP Oncology). "We look forward to continuing to advance this study to evaluate the potential role of TP-3654 as a monotherapy, in addition to exploring combination opportunities with JAK inhibitors, for patients with myelofibrosis." Below are the details for the SMP Oncology presentation: About TP-3654 TP-3654 is an oral investigational inhibitor of PIM 1 kinase, which has shown potential antitumor and anti-fibrotic activity through multiple pathways, including induction of apoptosis in preclinical models.2,3 TP-3654 was observed to inhibit proliferation and increased apoptosis in murine and human hematopoietic cells expressing clinically relevant JAK2V617F mutation.3 TP-3654 alone and in combination with ruxolitinib also showed normalized WBC and neutrophil counts, and reduced spleen size and bone marrow fibrosis in JAK2V617F and MPLW515L murine models of myelofibrosis.3 TP-3654 is currently being evaluated in a Phase 1/2 study of oral TP-3654 in patients with intermediate and high-risk myelofibrosis (NCT04176198). The Food and Drug Administration (FDA) granted Orphan Drug Designation for TP-3654 for the indication of myelofibrosis in May 2022. About Myelofibrosis Myelofibrosis is rare hematological malignancy with debilitating symptoms, splenic enlargement, cytopenia, and bone marrow fibrosis. The expression of PIM 1, which is known to contribute to cancer activation, is significantly elevated in hematopoietic cells from patients with myelofibrosis. It has been suggested to be a therapeutic target for myelofibrosis. About Sumitomo Pharma Oncology, Inc. Sumitomo Pharma Oncology, Inc. is a wholly owned subsidiary of Sumitomo Pharma Co., Ltd. As a global oncology organization with teams in the U.S. and Japan, SMP Oncology is committed to the goal of advancing purposeful science by transforming new discoveries into meaningful treatments for patients with cancer. SMP Oncology's robust and diverse pipeline of preclinical and clinical-stage assets spans multiple areas, including oncogenic pathways, survival mechanisms and novel protein interactions, which aim to address unmet clinical needs in oncology. For more information, visit . About Sumitomo Pharma Co., Ltd. Sumitomo Pharma Co., Ltd. is among the top-ten listed pharmaceutical companies in Japan, operating globally in major pharmaceutical markets, including Japan, the U.S., China, and other Asian countries with about 6,000 employees worldwide. Sumitomo Pharma Co., Ltd. defines its corporate mission as "To broadly contribute to society through value creation based on innovative research and development activities for the betterment of healthcare and fuller lives of people worldwide." Additional information about Sumitomo Pharma Co., Ltd. is available through its corporate website at . Disclaimer Regarding Forward-Looking Statements This press release contains "forward-looking statements," as that term is defined in the Private Securities Litigation Reform Act of 1995 regarding the research, development, and commercialization of pharmaceutical products. The forward-looking statements in this press release are based on management's assumptions and beliefs in light of information presently available and involve both known and unknown risks and uncertainties. Any forward-looking statements set forth in this press release speak only as of the date of this press release. We do not undertake to update any of these forward-looking statements to reflect events or circumstances that occur after the date hereof. Information concerning pharmaceuticals (including compounds under development) contained within this material is not intended as advertising or medical advice. References 1. Firas El Chaer, MD, Lindsay Rein, et al. Preliminary Data From the Phase 1/2 Study Of TP-3654, an Investigational Selective Pim1 Kinase Inhibitor, Showed Cytokine Reduction and Clinical Responses in Relapsed/Refractory Myelofibrosis. European Hematology Association (EHA) 2023 Hybrid Congress. 09 June 2023. 2. Foulks JM, Carpenter KJ, Luo B, et al. A small-molecule inhibitor of PIM kinases as a potential treatment for urothelial carcinomas. Neoplasia. 2014;16(5):403-412. 3. Nath D, Yang Y, Dutta A, Whatcott C. The PIM kinase inhibitor TP-3654 in combination with ruxolitinib exhibits marked improvement of myelofibrosis in murine models. Blood. 2018. 132(suppl 1):54. doi:10.1182/blood-2018-99-119421 SOURCE Sumitomo Pharma Oncology, Inc.