CD163

AGOURA HILLS, Calif., Jan. 16, 2024 (GLOBE NEWSWIRE) -- Oncotelic Therapeutics, Inc (OTCQB:OTLC) announced today the peer reviewed publication of Transforming Growth Factor Beta 2 (TGFB2) and Interferon Gamma Receptor 2 (IFNGR2) mRNA Levels in the Brainstem Tumor Microenvironment (TME) Significantly Impact Overall Survival in Pediatric DMG Patients in the Special Issue Gliomas: Signaling Pathways, Molecular Mechanisms and Therapeutic Approaches. "In light of our foundational discovery that elevated levels of TGF-B2 worsen mortality in various cancers, including Diffuse Midline Glioma (DMG), we have further elucidated the underlying mechanisms, particularly focusing on the impact of TGF-B2 on interferon signaling. We hope that sharing these findings from our research team will contribute to the eradication of cancer," stated Dr. Vuong Trieu, CEO and Chairman of Oncotelic. IFNGR2 is a critical component of the IFN-γ signaling pathway, playing a significant role in mediating the immune system's defense against cancer. Its function in enhancing immune surveillance and direct anti-tumor effects making its induction an attractive target for cancer immunotherapy- including suppression of TGF-B2 by OT-101. The article can be accessed for free online: https://www.mdpi.com/2227-9059/12/1/191 Abstract: This hypothesis-generating study characterized the mRNA expression profiles and prognostic impacts of antigen-presenting cell (APC) markers (CD14, CD163, CD86, and ITGAX/CD11c) in pediatric brainstem diffuse midline glioma (pbDMG) tumors. We also assessed the mRNA levels of two therapeutic targets, transforming growth factor beta 2 (TGFB2) and interferon gamma receptor 2 (IFNGR2), for their biomarker potentials in these highly aggressive pbDMG tumors. The expressions of CD14, CD163, and ITGAX/CD11c mRNAs exhibited significant decreases of 1.64-fold (p = 0.037), 1.75-fold (p = 0.019), and 3.33-fold (p < 0.0001), respectively, in pbDMG tumors relative to those in normal brainstem/pons samples. The pbDMG samples with high levels of TGFB2 in combination with low levels of APC markers, reflecting the cold immune state of pbDMG tumors, exhibited significantly worse overall survival outcomes at low expression levels of CD14, CD163, and CD86. The expression levels of IFNGR2 and TGFB2 (1.51-fold increase (p = 0.002) and 1.58-fold increase (p = 5.5 × 10−4), respectively) were significantly upregulated in pbDMG tumors compared with normal brainstem/pons samples. We performed multivariate Cox proportional hazards modelling that showed TGFB2 was a prognostic indicator (HR for patients in the TGFB2high group of pbDMG patients = 2.88 (1.12–7.39); p = 0.028) for poor overall survival (OS) and was independent of IFNGR2 levels, the age of the patient, and the significant interaction effect observed between IFNGR2 and TGFB2 (p = 0.015). Worse survival outcomes in pbDMG patients when comparing high versus low TGFB2 levels in the context of low IFNGR2 levels suggest that the abrogation of the TGFB2 mRNA expression in the immunologically cold tumor microenvironment can be used to treat pbDMG patients. Furthermore, pbDMG patients with low levels of JAK1 or STAT1 mRNA expression in combination with high levels of TGFB2 also exhibited poor OS outcomes, suggesting that the inclusion of (interferon-gamma) IFN-γ to stimulate and activate JAK1 and STAT1 in antitumor APC cells present the brainstem TME can enhance the effect of the TGFB2 blockade. 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, GMP Biotechnology Limited, melanoma (through CA4P), and Acute Myeloid Leukemia (through OXi 4503). Oncotelic acquired PointR Data Inc. in November 2019 to build an AI driven biotechnology company. Further, 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, erectile dysfunction, female sexual disorder and hypoactive sexual desire disorder. All these ailments have a very large population suffering from them and there is a need for treatments for each. For more information on AL-101, refer to our Annual Report on Form 10-K/A filed with the SEC on April 19, 2023. 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. 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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; building and the success of our nanoparticle platform and the related success of launching the platform, the development of the Company’s AI suite including but not limited to AI Chatbots, the public access to the Company’s AI suite, the success of the development of the AI suite or any other AI technologies and whether if any or portion thereof the Company’s AI suite or technologies will be commercialized and launched for sale. 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/A filed with the SEC on April 19, 2023 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 because of new information, future events, or otherwise. Contact Information: For Oncotelic Therapeutics, Inc.:Investor Relationsir@oncotelic.com

New positive data demonstrate oral AMT-101’s gut-restricted profile with tissue-level pharmacodynamics (PD) effects and no systemic exposure by design Translational analysis reveals IL-10 biological responses in both 3mg and 10mg dose arms SOUTH SAN FRANCISCO, Calif., March 03, 2023 (GLOBE NEWSWIRE) -- Applied Molecular Transport Inc. (Nasdaq: AMTI) (AMT) today announced additional Phase 2 data for oral AMT-101 in chronic pouchitis patients. AMT-101 is an investigational, once-daily, GI-selective, oral fusion of IL-10 and AMT’s proprietary carrier molecule, which is also in development for the treatment of rheumatoid arthritis (RA). AMT presented the data in Poster P584 Efficacy, Safety, and Tolerability of AMT-101: A Gut Selective Oral IL-10 Fusion in the Phase 2 FILLMORE Trial of Patients with Chronic Pouchitis at the European Crohn’s and Colitis Organisation (ECCO) ’23 Congress. “We are pleased to share these important new findings from the FILLMORE Phase 2 trial in patients with chronic pouchitis. We observed AMT-101’s immunomodulatory effect with enrichment of tissue FOXP3+ regulatory T cells (Tregs) and CD163+ macrophages (M2-macrophages) within the lamina propria. Tissue levels of IL-10 were also increased with both the 3mg and 10mg doses providing evidence of active transport,” said Bittoo Kanwar M.D., chief medical officer of AMT. “These insights further build on earlier positive top-line results demonstrating AMT-101’s safety profile and clinically meaningful responses in stool frequency and histologic healing in this severe patient population.” The FILLMORE Phase 2 double-blinded trial evaluated the safety and efficacy of orally administered AMT-101 monotherapy, over 12 weeks, in patients with chronic pouchitis. The FILLMORE trial randomized 22 patients to 3mg or 10mg of oral AMT-101. “These data further support advancement of once daily, oral AMT-101 for chronic pouchitis,” added Tahir Mahmood, Ph.D., chief executive officer and co-founder of AMT. “We remain focused on exploring a strategic partnership for this program and look forward to providing updates in the future.” About FILLMORE FILLMORE is a Phase 2 double-blinded trial that evaluated the safety and efficacy of orally administered AMT-101 monotherapy, over 12 weeks, in patients with chronic pouchitis. The FILLMORE trial randomized 22 patients to 3mg or 10mg of oral AMT-101. The trial was conducted across 33 sites and 11 countries in patients with daily stool frequency ≥ 6 (and > 3 stools per day more than baseline), Modified Pouchitis Disease Activity Index (mPDAI) score ≥ 5, and histological evidence of pouchitis (Geboes ≥ 3.1), among other entry criteria. Patients must have failed at least one round of antibiotic therapy and no lead-in or rescue antibiotic therapy was allowed. About Pouchitis Approximately 30% of patients with UC eventually require total colectomy. Ileal pouch-anal anastomosis (IPAA) is the surgical treatment of choice as it avoids permanent ileostomy and is associated with better quality of life outcomes. Up to 60,000 patients in the U.S. alone experience pouchitis, inflammation in the lining of the pouch, after IPAA surgery. Acute pouchitis often responds to antibiotic treatment but up to 50% of pouchitis patients develop chronic pouchitis where patients often relapse on or do not respond to antibiotic therapy. Pouchitis is characterized by clinical symptoms of excessive stool frequency, urgency, fecal incontinence, nocturnal seepage and lower abdominal pain. Pouchitis is an orphan indication with no current FDA-approved products. About AMT-101 AMT-101 is a novel GI-selective, oral fusion of IL-10 and AMT’s proprietary carrier molecule, currently in development in Phase 2 clinical trials for chronic pouchitis and RA. AMT-101 is designed to cross the intestinal epithelial (IE) barrier with limited entry into the bloodstream, thereby focusing IL-10 at the primary site of inflammation in IBD, along the intestinal tissue lamina propria, potentially avoiding the side effects observed with systemic administration. U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation for AMT-101 in patients with pouchitis. About Applied Molecular Transport Inc. AMT is a clinical-stage biopharmaceutical company developing novel oral biologic product candidates, by leveraging its technology platform to design biologic product candidates in patient friendly oral dosage forms. AMT’s product candidates are designed to precisely target the relevant pathophysiology of disease. AMT’s proprietary technology platform is incorporated in its product candidates, exploiting existing natural cellular trafficking pathways to drive the active transport of diverse therapeutic modalities across the IE barrier. Active transport is an efficient mechanism that utilizes the cell’s own machinery to transport materials across the IE barrier. AMT’s headquarters, internal GMP manufacturing and lab facilities are located in South San Francisco, CA. For additional information on AMT, please visit www.appliedmt.com. Forward-Looking Statements This press release contains forward-looking statements as that term is defined in Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. Such forward-looking statements involve substantial risks and uncertainties. All statements other than statements of historical facts contained in this press release are forward-looking statements including statements relating to AMT’s plans and prospects, expectations, forecasts and future events. Such forward-looking statements include, but are not limited to, the potential of, and expectations regarding AMT’s technology platform, statements regarding the potential of AMT-101 or regarding AMT-101 clinical trials, statements regarding advancing product candidates to future phases of development, our ability to obtain regulatory approval for AMT’s product candidates, and program updates, the potential for strategic partnerships and other strategic transactions, milestones for AMT’s clinical trials, including potentially advancing AMT-101 for chronic pouchitis, and AMT’s ability to replicate past clinical development strategies, statements regarding the potential for AMT’s product candidates to treat or provide clinically meaningful outcomes for certain medical conditions or diseases, statements regarding the mechanism of action of AMT’s product candidates and the potential to avoid side effects with our product candidates, statements regarding the market opportunity for AMT’s product candidates, including the potential pouchitis market and statements by AMT’s chief medical officer and chief executive officer and co-founder. In some cases, you can identify forward-looking statements by terminology such as “believe,” “estimate,” “intend,” “may,” “plan,” “potentially,” “will,” “expect,” “enable,” “likely” or the negative of these terms or other similar expressions. We have based these forward-looking statements largely on our current expectations and projections about future events and trends that we believe may affect our financial condition, results of operations, business strategy and financial needs. Actual events, trends or results could differ materially from the plans, intentions and expectations disclosed in these forward-looking statements based on various factors. Information regarding the foregoing and additional risks may be found in the section entitled “Risk Factors” in AMT’s Annual and Quarterly Reports on Form 10-K and 10-Q filed with the Securities and Exchange Commission (the “SEC”), and AMT’s future reports to be filed with the SEC. These forward-looking statements are made as of the date of this press release, and AMT assumes no obligation to update the forward-looking statements, or to update the reasons why actual results could differ from those projected in the forward-looking statements, except as required by law. Investor Relations Contact:Andrew ChangHead, Investor Relations & Corporate Communicationsachang@appliedmt.com Media Contacts:Alexandra SantosWheelhouse Life Science Advisorsasantos@wheelhouselsa.com Aljanae ReynoldsWheelhouse Life Science Advisorsareynolds@wheelhouselsa.com

SOUTH SAN FRANCISCO, Calif., Dec. 07, 2022 (GLOBE NEWSWIRE) -- NGM Biopharmaceuticals, Inc. (NGM Bio) (Nasdaq: NGM), a biotechnology company focused on discovering and developing transformative therapeutics for patients, today announced the presentation of preliminary data from the Phase 1 Part 1a monotherapy dose escalation arm of the ongoing Phase 1/2 trial of NGM707 in patients with advanced or metastatic solid tumors at the European Society for Medical Oncology Immuno-Oncology (ESMO I-O) Annual Congress, which is taking place December 7 – 9, 2022 in Geneva, Switzerland. In the poster presentation titled, “First-in-Human Study of NGM707, an ILT2/ILT4 Dual Antagonist Antibody in Advanced or Metastatic Solid Tumors: Preliminary Monotherapy Dose Escalation Data” (#174P), NGM707 was generally well tolerated across all dose cohorts and demonstrated promising early signals of anti-tumor activity. Of 24 response-evaluable patients in the Part 1a arm, best overall responses as of November 23, 2022 are partial response in one patient, stable disease in six patients and non-complete response/non-progressive disease in one patient. Six patients had reduced target lesion size including a maximum decrease in one patient of 70%. A copy of the presentation presented at the ESMO I-O Annual Congress is available on NGM Bio’s website at https://www.ngmbio.com/discovery-engine/publications/. The Phase 1 portion of the ongoing NGM707 trial includes a monotherapy dose escalation arm (Part 1a) and a dose-finding arm in combination with pembrolizumab (KEYTRUDA®) (Part 1b). The Phase 2 portion of the trial will include expansion cohorts of patients treated with NGM707 in combination with KEYTRUDA (Part 2b) in several advanced solid tumor types. The Part 1a arm enrolled patients into escalating NGM707 dose cohorts (6 mg to 1800 mg) administered intravenously every three weeks. Enrolled patients received a median of four prior lines of therapy, and all had metastatic disease. Primary objectives in the Phase 1 portion are to assess safety and tolerability of NGM707 and to identify Phase 2 doses. Secondary/exploratory objectives include assessment of PK/biomarker correlation, immunogenicity, and preliminary antitumor activity per RECIST v1.1. As of a November 23, 2022 data cut-off, 34 patients have been enrolled in the monotherapy dose escalation. Of 24 response-evaluable patients (those completing at least one on-treatment scan), best overall responses are partial response (PR) in one patient, stable disease in six patients and non-complete response/non-progressive disease in one patient. Six of the 24 response-evaluable patients experienced target lesion reduction. The patient experiencing the PR had a target lesion decrease of 70%, along with a reduction and/or elimination of non-target lesions. These responses were seen across five distinct tumor types. Preliminary evidence of potential myeloid reprogramming was observed in peripheral non-classical monocytes as well as in tumor biopsies, with reduction of the M2 macrophage marker CD163 observed post-treatment. Treatment-related adverse events (TRAEs) occurred in 47% of patients, with 9% of patients experiencing Grade ≥3 TRAEs. One dose-limiting toxicity of pneumonitis (G5) in a patient with pulmonary metastasis was observed at NGM707 600 mg. A maximum tolerated dose was not reached. As of November 23, 2022, four patients remain on NGM707 monotherapy treatment in the Part 1a arm, including the patient experiencing the PR. Enrollment is ongoing in the Part 1b arm evaluating NGM707 in combination with KEYTRUDA. NGM Bio anticipates enrolling approximately 220 patients in the Phase 1/2 trial of NGM707. “NGM707 is designed to reprogram immune-suppressive ILT4- and ILT2-expressing myeloid cells and ILT2-expressing lymphoid cells in the tumor microenvironment into immune-stimulatory cells that will promote anti-tumor activity. We’re pleased to present these initial data demonstrating a favorable tolerability profile for NGM707 as well as early, yet promising signals that this mechanistic approach may translate to clinical benefit,” said Dan Kaplan, Ph.D., Head of Translational Immuno-Oncology at NGM Bio. “We’re particularly encouraged to see clinical benefit in certain patients in response to monotherapy treatment with NGM707, and we look forward to evaluating NGM707’s potential effect when combined with T cell checkpoint inhibition in Part 1b of the study, which is now underway.” About NGM707 ILT2 and ILT4, inhibitory receptors with enriched expression on myeloid cells in the tumor microenvironment, are myeloid checkpoints that may enable certain tumors to evade immune detection, thereby suppressing patients’ anti-tumor responses. NGM707 is being developed with the goal of improving patient immune response to tumors by inhibiting both ILT2 and ILT4. By inhibiting both ILT2 and ILT4, NGM707 may be able to overcome the potential redundant role the two receptors play where they are co-expressed in myeloid cells and reprogram those cells to enhance T cell activity and proliferation. In addition, ILT2 blockade may drive further benefit through reducing suppression in certain lymphoid cells capable of directly attacking tumor cells. About NGM Bio’s Oncology Portfolio NGM Bio’s currently disclosed oncology product candidates are all derived from the company’s in-house discovery engine and are wholly owned by NGM Bio. These oncology programs include: NGM120, a GFRAL antagonist antibody in a Phase 2 trial for the treatment of metastatic pancreatic cancer; NGM707, an ILT2/ILT4 (LILRB1/LILRB2) dual antagonist antibody in a Phase 1/2 trial for the treatment of advanced or metastatic solid tumors; NGM831, an ILT3 (LILRB4) antagonist antibody in a Phase 1 trial in advanced solid tumors; and NGM438, a LAIR1 antagonist antibody in a Phase 1 trial in advanced solid tumors. Abbreviations (in Alphabetical Order) GFRAL= Glial Cell-derived Neurotrophic Factor Receptor Alpha-like; ILT2=Immunoglobulin-Like Transcript 2; ILT3=Immunoglobulin-Like Transcript 3; ILT4=Immunoglobulin-Like Transcript 4; LAIR1= LAIR1=Leukocyte-Associated Immunoglobulin-Like Receptor 1; LILR=Leukocyte Immunoglobulin-Like Receptor [ILT2 = LILRB1, ILT3=LILRB4, ILT4=LILRB2]; LIR=Leukocyte Immunoglobulin-Like Receptor. About NGM Bio NGM Bio is focused on discovering and developing novel, life-changing medicines for people whose health and lives have been disrupted by disease. The company’s biology-centric drug discovery approach aims to seamlessly integrate interrogation of complex disease-associated biology and protein engineering expertise to unlock proprietary insights that are leveraged to generate promising product candidates and enable their rapid advancement into proof-of-concept studies. As explorers on the frontier of life-changing science, NGM Bio aspires to operate one of the most productive research and development engines in the biopharmaceutical industry. All therapeutic candidates in the NGM Bio pipeline have been generated by its in-house discovery engine, always led by biology and motivated by unmet patient need. Today, the company has seven programs in clinical development, including four in Phase 2 or 2b studies, including the recently completed NGM621 CATALINA trial, across three therapeutic areas: cancer, retinal diseases and liver and metabolic diseases. Visit us at www.ngmbio.com for more information. KEYTRUDA® is a registered trademark of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.