CD163

– In preclinical studies, CHS-1000 shows a high affinity for human ILT4, reverses ILT4-mediated immunosuppressive functions, leading to activation of immune cells and increased cytokine secretion – – Mechanism may enhance antitumor responses with immunotherapy – – First novel immuno-oncology product candidate discovered and developed by Coherus – – The CHS-1000 IND submission is planned for Q2 2024 – REDWOOD CITY, Calif., April 08, 2024 (GLOBE NEWSWIRE) -- Coherus BioSciences, Inc. (Coherus, Nasdaq: CHRS), today presented preclinical data for its immuno-oncology pipeline candidate, CHS-1000, a novel ILT4 monoclonal antibody, at the 2024 AACR Annual Meeting being held in San Diego, California. Data presented show CHS-1000 is a potent monoclonal antibody that binds selectively to human ILT4 (also known as LILRB2) with high affinity, efficiently blocking interaction with its ligands and reversing immunosuppressive functions, leading to activation of human dendritic cells and T cells and promoting polarization of macrophages to an inflammatory M1 phenotype. “Myeloid cell-mediated immunosuppression in the tumor microenvironment is a major contributor to tumor immune invasion and PD-1 resistance. The data presented in this poster demonstrate the potential for CHS-1000 to reverse myeloid suppression and activate an inflammatory immune response. Reprogramming myeloid cells in the tumor microenvironment holds promise as a new immuno-therapy approach with the aim to overcome resistance to I-O therapy and potentially provide benefit to more cancer patients,” said Theresa LaVallee, Ph.D., Chief Development Officer at Coherus. “CHS-1000 is our first internally discovered development candidate, and we are excited to be filing the IND this quarter. We plan to advance CHS-1000 into the clinic both as a single agent and in combination with LOQTORZI®.” These data will be presented today in a poster session, and the poster will be available for download at the time of the presentation: Abstract: 1364/15 Title: Characterization of CHS-1000, an Fc-modified anti-ILT4 monoclonal antibody for reprogramming suppressive myeloid cells in solid tumors Presenting author: Narendiran Rajasekaran, Ph.D. Session PO.IM01.02 – Immune Checkpoints and Inhibitory Molecules 1 Date and Time: Monday, April 8, 2024, 9:00 a.m. – 12:30 p.m. Pacific Daylight Time Poster data are summarized as follows: CHS-1000 binds specifically and selectively to human ILT4 (LILRB2) with high affinity and showed no cross-reactivity to other LILRB family members. CHS-1000 efficiently blocks the interaction of ILT4 with its ligands, HLA-A and HLA-G, and reverses ILT4-mediated immunosuppressive functions, leading to activation of M1 macrophages, dendritic cells, and T cells and increases in pro-inflammatory cytokine secretion in in vitro assays. CHS-1000 is Fc silent and lacks effector function activity in in vitro assays consistent with the engineered modification of the Fc region of the antibody. It also has IgG1‑like PK parameters in human FcRn transgenic mice. ILT4 and CD163, a marker of suppressive (M2) macrophages, are highly expressed in a broad range of solid tumors. About CHS-1000 Discovered and developed by Coherus, CHS-1000 is a novel humanized Fc-modified IgG1 monoclonal antibody specifically targeting ILT4 (LILRB2). CHS-1000 is designed to overcome myeloid cell-mediated immunosuppression and resistance in the tumor microenvironment. In preclinical studies, CHS-1000 promotes repolarization of suppressive M2 macrophages to a pro-inflammatory M1 phenotype and enhances activation of dendritic cells and T cells in vitro. Coherus plans to investigational new drug (IND) application in Q2 2024 and begin clinical studies later this year. About Coherus BioSciences Coherus is a commercial-stage biopharmaceutical company focused on researching, developing, and commercializing innovative immunotherapies to treat cancer. Coherus is developing an innovative immuno-oncology pipeline that will synergize with its proven commercial capabilities in oncology. Coherus’ immuno-oncology pipeline includes multiple antibody immunotherapy candidates focused on enhancing the innate and adaptive immune responses to enable a robust immunologic response and enhance outcomes for patients with cancer. Casdozokitug is a novel anti-IL-27 antibody currently being evaluated in two ongoing clinical studies: a Phase 1/2 study in advanced solid tumors and a Phase 2 study in hepatocellular carcinoma. CHS-114 is a highly selective, competitively positioned, ADCC-enhanced anti-CCR8 antibody currently in a Phase 1/2 study as a monotherapy in patients with advanced solid tumors. CHS-1000 is a preclinical candidate targeting immune-suppressive mechanisms via the novel pathway ILT4, with an IND filing planned in Q2 2024. Coherus markets LOQTORZI® (toripalimab-tpzi), a novel next-generation PD-1 inhibitor, UDENYCA® (pegfilgrastim-cbqv), a biosimilar of Neulasta®, and YUSIMRY® (adalimumab-aqvh), a biosimilar of Humira®. Neulasta® is a registered trademark of Amgen, Inc. Humira® is a registered trademark of AbbVie Inc. Forward-Looking Statements Except for the historical information contained herein, the matters set forth in this press release are forward-looking statements within the meaning of the "safe harbor" provisions of the Private Securities Litigation Reform Act of 1995, including, but not limited to, statements regarding Coherus’ ability to identify synergies between its I-O pipeline and its commercial capabilities; Coherus’ expected timing for filing an IND for CHS-1000; Coherus’ expectations to be able to advance its candidates through clinical trials; and Coherus’ expectations that its immunotherapy candidates will enhance outcomes for patients with cancer. Such forward-looking statements involve substantial risks and uncertainties that could cause Coherus’ actual results, performance, or achievements to differ significantly from any future results, performance, or achievements expressed or implied by the forward-looking statements. Such risks and uncertainties include, among others, the risks and uncertainties inherent in the preclinical and clinical drug development process; risks related to Coherus’ existing and potential collaboration partners; risks of Coherus’ competitive position; the risks and uncertainties of the regulatory approval process, including the speed of regulatory review and the timing of Coherus’ regulatory filings; the risk of FDA review issues; the risks of competition; the risk that Coherus is unable to complete commercial transactions; and the risks and uncertainties of possible litigation. All forward-looking statements contained in this press release speak only as of the date of this press release. Coherus undertakes no obligation to update or revise any forward-looking statements. For a further description of the significant risks and uncertainties that could cause actual results to differ from those expressed in these forward-looking statements, as well as risks relating to Coherus’ business in general, see Coherus’ Annual Report on Form 10-K for the fiscal year ended December 31, 2023 filed with the Securities and Exchange Commission on March 15, 2024, including the section therein captioned “Risk Factors” and in other documents Coherus files with the Securities and Exchange Commission. UDENYCA®, YUSIMRY®, and LOQTORZI®, whether or not appearing in large print or with the trademark symbol, are trademarks of Coherus, its affiliates, related companies or its licensors or joint venture partners unless otherwise noted. Trademarks and trade names of other companies appearing in this press release are, to the knowledge of Coherus, the property of their respective owners. Coherus Contact Information: For Investors: Jami Taylor Head of Investor Relations IR@coherus.com For Media: Jodi Sievers VP, Corporate Communications media@coherus.com

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. 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; 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