SHP1

Reduction of key proteins in the interleukin 4 (IL-4) and IL-13 signalling pathway via SHP-1 activation is a key component involved in the mechanism of action of ‘1104First-in-class upstream approach uniquely affects both the effector and regulatory arms of the immune response, helping to restore immune homeostasisCompelling subcutaneous data verifies the continued advancement of a differentiated commercial dosage form of ‘1104 Previous Phase 2a trials showed improvement in key clinical measures in patients with eosinophilic esophagitis (EoE) and other allergic diseases GAITHERSBURG, Md. and CAMBRIDGE, United Kingdom, July 24, 2024 (GLOBE NEWSWIRE) -- Revolo Biotherapeutics Limited (“Revolo”) today announced new data from preclinical studies and previously completed clinical trials that further elucidate the upstream mechanism of action (MOA) of ‘1104, which uniquely affects both the effector and regulatory arms of the immune response. The data confirms that ‘1104 binds to a novel receptor through selective upstream binding to allergic antigen-presenting cells (APCs) which reduces IL-4 and IL-13 signaling pathways. ‘1104 also rapidly upregulates activated T regulatory (Tregs) and activated B regulatory cells (Bregs) for multiple weeks, which can restore immune homeostasis and support less frequent dosing regimens. Additional positive animal data assessing a subcutaneous (SC) dosage form of ‘1104 verifies the continued development of a differentiated SC commercial formulation. In animal models of allergic disease, ‘1104 SC delivery performed as well as intravenous administration. The newly generated data validates the prioritization of the ‘1104 SC development program, with plans to initiate bridging clinical studies in 2025. “It is well documented that targeted downstream therapies can fail to translate eosinophil reduction at the tissue-level into meaningful clinical responses, creating a large unmet need for novel therapies,” said Kari Brown, Executive Vice President of Clinical Development, Operations and Strategy at Revolo. “We are excited to shed more light on the upstream signaling pathways engaged by ‘1104 which show its ability to engage the effector and regulatory arms of the immune response. These new data demonstrate the potential of ‘1104 to treat a range of allergic diseases.” Woody Bryan, President and Chief Executive Officer of Revolo, added, “At Revolo, our priority has been to develop a differentiated product for patients with allergic diseases. The SC administration of ‘1104 will offer a patient-friendly treatment. Additionally, based on encouraging animal data, we are evaluating the potential for sublingual administration, which will further elevate the competitive commercial profile of ‘1104 and improve patient convenience. We look forward to sharing data in the future.” Previously announced positive data that supports the clinical potential of ‘1104 include:In a Phase 2a clinical trial (RVLO 121-04) evaluating the efficacy, safety, and tolerability of ‘1104 in adults with active eosinophilic esophagitis (EoE): Treatment with ‘1104 led to a statistically significant separation from baseline in key clinical endpoints and a rapid translation into a clinical response per the patient-reported outcome of the Dysphagia Severity Questionnaire (DSQ).The data substantiates that 1104’s upstream MOA offers a first-in-class modality that overcomes the shortfall of other downstream approaches that have impacted histologic endpoints but failed to show clinical response. In a Phase 2a trial mapping study in allergic individuals subjected to nasal and skin allergen challenges (RVLO 121-05) data demonstrated: Rapid reduction (Day 1) in intradermal allergic inflammation.Sustained activation of Tregs and Bregs, providing additional clinical validation of its MOA with persistence to at least 28 days. About ‘1104‘1104 is a first-in-class peptide that is involved in restoring immune homeostasis. Revolo has recently advanced ‘1104 through two Phase 2a trials: one in patients with eosinophilic esophagitis (EoE) and one in patients with allergen sensitivity while exploring its potential for other allergic diseases. Revolo is planning to advance a commercially differentiated SC dosage form into clinical studies for EoE and other type 2 allergic conditions. About Revolo BiotherapeuticsRevolo is developing therapies that work upstream in the immune cascade for the treatment of autoimmune and allergic diseases, without the immune system suppression seen with current therapies. Its two drug candidates, ‘1805 and ‘1104, a protein and a peptide respectively, restore immune homeostasis to prevent the chronic pro-inflammatory immune response that results in autoimmune or allergic disease. The disease-agnostic mechanism of action of Revolo Biotherapeutic’s assets provides a potential platform for the development of treatments for multiple autoimmune and allergic diseases.For further information, please visit www.revolobio.com. Company ContactWoody Bryan, Ph.D.President and CEOwbryan@revolobio.com Media ContactMichael RubensteinLifeSci Communications+1 561-289-7981mrubenstein@lifescicomms.com

– Data demonstrate distinct IL-27-mediated expression of genes associated with immune suppression in vitro, supporting ongoing clinical development of first-in-class anti-IL-27 antibody casdozokitug – – Anti-CCR8 antibody, CHS-114, depletes tumor-infiltrating Treg cells and activates NK cells in dissociated head and neck squamous cell carcinoma (HNSCC) tumors – – Anti-PD-1 antibody, LOQTORZI™ (toripalimab-tpzi), exhibits potent T cell activation; in combination with chemotherapy shows enhanced clinical efficacy irrespective of PD-L1 status across multiple tumor types – REDWOOD CITY, Calif., Nov. 03, 2023 (GLOBE NEWSWIRE) -- Coherus BioSciences, Inc. (Coherus, Nasdaq: CHRS), today announced data from three immuno-oncology pipeline programs at the 38th Annual Meeting of SITC taking place November 1 - 5, 2023 at the San Diego Convention Center in San Diego, CA. Preclinical data presented support differentiated mechanisms of its next-generation immunotherapies potentially enabling the antitumor immune activation in more cancer patients and enhanced treatment outcomes. “These data presented at SITC highlight the complementary mechanisms that we have in our innovative immunotherapy portfolio, including anti-PD-1, anti-IL27 and anti-CCR8, and the promise of novel immuno-oncology treatment combinations that may overcome the challenging tumor microenvironment,” said Theresa LaVallee, Ph.D., Coherus’ chief development officer. “LOQTORZI™ is the first approved treatment option for patients with nasopharyngeal carcinoma (NPC), and we will continue to generate and use data to optimize our clinical development plans through the selection of additional tumor types and immuno-oncology combinations that can have the greatest impact on extending survival for cancer patients.” Casdozokitug (CHS-388, formerly SRF388), a first-in-class anti-IL-27 antibodyInterleukin (IL)-27 is an immunoregulatory cytokine involved in resolving inflammation and inhibiting anti-tumor immune responses. Blocking IL-27 with casdozokitug in clinical trials has led to monotherapy tumor growth inhibition and partial responses in patients with non-small cell lung cancer (NSCLC) and renal cell carcinoma (RCC) (NCT04374877) and ongoing trials are studying combinations with PD-1/PD-L1 pathway blockade in NSCLC and hepatocellular carcinoma (HCC). Data presented at SITC 2023 demonstrate IL-27-mediated gene expression, highlighting its critical role in immune suppressive mechanisms in the tumor microenvironment and importance as a new target for cancer treatment, as well as an opportunity to identify biomarkers that could determine patients most likely to respond to anti-IL-27 treatment. Abstract #1351: Identifying IL-27 dependent biomarkers in lymphocytes, NK cells, and myeloid cells in peripheral blood and the tumor microenvironmentDate and Time: Friday, November 3, 9 a.m.–7 p.m. Pacific Daylight Time (PDT)Location: Exhibit Halls A and B1 – San Diego Convention Center Poster presentation data are summarized as follows: In human immune cells from peripheral blood, IL-27 induces the expression of interferon (IFN)-stimulated genes, which are associated with drug resistance in cancerAlthough many known IFN-responsive genes were induced by both IFNs and IL-27 treatment, distinct gene expression was observed in different immune cell typesIL-27 and IFNs induce unique gene expression in different cell types, for example, GBP5 (guanylate-binding protein 5) and IRF1 (interferon regulatory factor 1), two interferon stimulated genes, are preferentially elevated by IL-27 in NK cells and CD8+ T cellsImmunohistochemistry (IHC) analysis of treatment-naïve NSCLC tumor samples showed that IL-27+ macrophages are co-localized with GBP5+ T-cell-rich areas in the TMEThese studies lend insights into the immune interplay between IFNs and IL-27 signaling across different immune cells and within the TME and ascertain the immunosuppressive role of IL-27 and may inform casdozo clinical development. CHS-114 (formerly SRF114), an anti-CCR8 antibodyCCR8 is a chemokine receptor predominantly expressed by tumor infiltrating Tregs that suppress the body’s natural anti-cancer immune response. Targeting CCR8 is a promising potential therapeutic strategy designed to deplete Tregs, reshape the tumor microenvironment and enhance anti-tumor immune response. CHS-114 is designed to selectively target human CCR8 and preferentially depletes CCR8+ Treg cells and not T effector (Teff) cells in tumors or normal tissue. Data presented demonstrate the role of CCR8+ Tregs as dominant immunosuppressive cells in the TME and highlight head and neck squamous cell carcinoma (HNSCC) as a promising tumor type in which CHS-114 could have anti-tumor activity as monotherapy or in combination with an anti-PD1 antibody. CHS-114 is currently being evaluated in a Phase 1 clinical trial (NCT05635643). Abstract #1354: Anti-CCR8 antibody SRF114 depletes tumor-infiltrating regulatory T cells in dissociated tumors from patients with head and neck squamous cell carcinomaDate and Time: Saturday, November 4, 9 a.m.–8:30 p.m. PDTLocation: Exhibit Halls A and B1 – San Diego Convention Center Poster presentation data are summarized as follows: Chemokine receptor 8 (CCR8) expression is highly enriched on intratumoral Tregs within the TME cells, particularly in HNSCCIn multiple model systems, CHS-114, a cytolytic antibody selective for CCR8, activates natural killer (NK) cells and specifically induces NK-mediated cytotoxicity against tumor-infiltrating CCR8+ Tregs and results in the expansion of effector CD8 T cellsEnhanced antitumor immunity is observed with combination of Anti-CCR8 and anti-PD-1 combination treatmentCHS-114, a CCR8-specific cytotoxicity-inducing antibody that preferentially depletes CCR8+ Treg cells and not T effector (Teff) cells, is currently being evaluated in a Phase 1 clinical trial (NCT05635643). LOQTORZI™ (toripalimab-tpzi), a next generation anti-PD-1 antibodyPD-L1 is a protein found on the surface of some cancer cells that can help evade the body’s immune system by suppressing T cell activation and inhibiting the T cell’s ability to kill cancer cells. LOQTORZI™ is an anti-PD-1 monoclonal antibody that blocks PD-L1 binding to the PD⁠-⁠1 receptor at a unique site with high affinity to activate antitumor immunity. Data presented compare mechanistic data for LOQTORZI™ to commercially available anti-PD-1 monoclonal antibodies and demonstrate higher expression of key immune system biomarkers with LOQTORZI™. Additionally, LOQTORZI™ in combination with chemotherapy shows enhanced clinical efficacy irrespective of PD-L1 status across multiple tumor types in post hoc analyses of 3 randomized controlled clinical trials in NPC, NSCLC and esophageal squamous-cell carcinoma (ESCC). LOQTORZI™ (toripalimab-tpzi) was recently approved by the U.S. Food and Drug Administration (FDA) for metastatic or recurrent NPC as first-line treatment in combination with chemotherapy or as second- or greater-line monotherapy treatment. Abstract #468: Characteristics of toripalimab: a next generation anti-PD-1 antibody with potent T cell activation and enhanced clinical efficacy irrespective of PD-L-1 statusDate and Time: Saturday, November 4, 9 a.m.–8:30 p.m. PDTLocation: Exhibit Halls A and B1 – San Diego Convention Center Poster presentation data are summarized as follows: Toripalimab in combination with chemotherapy demonstrates clinical efficacy irrespective of PD-L1 statusToripalimab exhibits a 12-fold higher binding affinity to PD-1 compared to pembrolizumabToripalimab promotes a stronger Th1-mediated response than pembrolizumab in vitro in human peripheral blood mononuclear cells (PBMCs)Toripalimab induced an elevated IFN- gene signature in NSCLC dissociated tumor cells with different kinetics and higher intensity compared to pembrolizumabIn comparison to other commercially available anti-PD-1 antibodies, toripalimab exhibits the lowest potential for partial agonism by recruiting low levels of SHP1 and SHP2, negative regulators of T cell activation About LOQTORZI™ (toripalimab-tpzi)LOQTORZI™ is a next generation anti-PD-1 monoclonal antibody that blocks PD-L1 binding to the PD⁠-⁠1 receptor at a unique site with high affinity and activates antitumor immunity demonstrating improvement in the overall survival of cancer patients in several tumor types.For more information, please see LOQTORZI.com for FDA-approved indications and full prescribing information. About CasdozokitugCasdozokitug (formerly SRF388) is a first-in-class human anti-IL-27 antibody designed to inhibit the activity of this immunosuppressive cytokine. Particular tumor types have been identified where IL-27 appears to play an important role in the immunosuppressive tumor microenvironment and may contribute to resistance to treatment with checkpoint inhibitors. Furthermore, a potential biomarker associated with IL-27 has been identified that may be useful in helping identify patients most likely to respond to casdozokitug. It is the first IL-27 antibody to enter the clinic. About CHS-114CHS-114 (formerly SRF114) is a human, cytolytic anti-CCR8 antibody designed to preferentially deplete CCR8+ Treg cells within the tumor microenvironment and not T effector (Teff) calls in normal tissue. In preclinical studies, CHS-114 induced antibody-dependent cellular cytotoxicity (ADCC) and/or antibody-dependent cellular phagocytosis (ADCP) pathways to deplete intertumoral Treg cells. In addition, CHS-114 reduced tumor growth in murine models. CHS-114 is currently being evaluated in a Phase 1 clinical trial (NCT05635643) as a therapeutic candidate that holds the potential to drive anti-tumor immunity in patients. About Coherus’ Immuno-oncology PipelineCoherus is developing an innovative immuno-oncology pipeline that will be synergistic with its proven commercial capabilities in oncology. The foundational therapy in our immuno-oncology pipeline is LOQTORZI™ (toripalimab-tpzi), a next-generation, FDA-approved PD-1 inhibitor. Through its acquisition of Surface Oncology, Coherus’ immuno-oncology pipeline now 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 (formerly SRF388) is a novel anti-IL-27 antibody currently being evaluated in Phase 1/2 clinical trials in lung and liver cancer. CHS-114 (formerly SRF114) 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. Coherus’ earlier-stage immuno-oncology pipeline targets immune-suppressive mechanisms in the tumor microenvironment, including CHS-006, a TIGIT-targeted antibody, being evaluated in a Phase 1/2 clinical trial in combination with toripalimab in patients with advanced solid tumors, and CHS-1000, a preclinical program targeting the novel pathway ILT4. About Coherus BioSciencesCoherus is a commercial-stage biopharmaceutical company focused on the research, development and commercialization of innovative immunotherapies to treat cancer. Coherus is developing an innovative immuno-oncology pipeline that will be synergistic with its proven commercial capabilities in oncology. Coherus markets UDENYCA® (pegfilgrastim-cbqv), a biosimilar of Neulasta®, CIMERLI® (ranibizumab-eqrn), a biosimilar of Lucentis®, YUSIMRY™ (adalimumab-aqvh), a biosimilar of Humira® and expects to launch LOQTORZI™ (toripalimab-tpzi), a novel next generation PD-1 inhibitor, in the U.S. in Q1 2024. 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 realize synergies between its commercial capabilities in oncology and its immuno-oncology pipeline; Coherus’ expectations of the launch timing for LOQTORZI™; expectations about the timing and ability of Coherus to advance the development of its product candidates; and Coherus’ expectation that its product candidates may advance treatment outcomes for patients. 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 clinical drug development process; risks related to integration of Surface’s programs and operations; risks related to realizing the anticipated benefits of the acquisition of Surface; 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, international aspects of Coherus’ business and the timing of Coherus’ regulatory filings; the risk of FDA review issues; the risk that Coherus is unable to complete commercial transactions and other matters that could affect the availability or commercial potential of Coherus’ products and product candidates; 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’ Quarterly Report on Form 10-Q for the fiscal quarter ended June 30, 2023 filed with the Securities and Exchange Commission on August 2, 2023, including the section therein captioned “Risk Factors” and in other documents Coherus files with the Securities and Exchange Commission. UDENYCA®, CIMERLI®, 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: Investors:Jami Taylor, VP, Investor Relationsir@coherus.com Media:Jodi Sievers, VP Corporate Communicationsmedia@coherus.com

- Preclinical data identify SHP-1 as a downstream effector of GDF-15-mediated inhibition of T cell adhesion, further elucidating mechanistic details of GDF-15’s role in immunotherapy resistance. - Combination of visugromab and bispecific T-cell engager significantly increased the number of intratumoral T cells in a mouse tumor model, providing a strong rationale to further investigate this combination approach. - Preclinical data continue to expand the potential of GDF-15 neutralizing therapy, supporting its role as a critical component for treatment success in a broad range of anti-cancer regimens. MUNICH--(BUSINESS WIRE)-- CatalYm today announced the presentation of two preclinical data sets expanding the mechanistic understanding and clinical application of its lead anti-GDF-15 antibody candidate, visugromab, at the upcoming Society for Immunotherapy of Cancer (SITC) 2023 Annual Meeting in San Diego, USA. The findings will be presented in two poster sessions on Friday, November 3rd, and Saturday, November 4th, and provide further clarification on GDF-15-mediated inhibition of T cell infiltration and highlight the potential of combining visugromab with bispecific T-cell engagers as a novel approach in cancer therapy. Visugromab is currently evaluated in a broad Phase 2 program in combination with anti-PD-1 treatment in multiple solid tumor indications. “We are advancing our understanding of the underlying molecular mechanisms that are the foundation for GDF-15’s central role in tumor resistance to immunotherapy and visugromab’s potential to reinstate anti-tumor activity and enhance responses,” said Dr. Christine Schuberth-Wagner, Chief Scientific Officer at CatalYm. “The new data for the combination of visugromab with bispecific T-cell engagers provide strong scientific support for a synergistic effect in this novel therapeutic setting. We will further investigate this combination, which could extend durability and improve outcomes for a broad range of cancer patients with high medical need.” Poster Presentation Identifying SHP-1 as Central Mediator of GDF-15-related T Cell Adhesion Inhibition The first data set further expands understanding of visugromab’s mechanism of action and the underlying pathways involved in the development of GDF-15-mediated therapy resistance in cancer cells. When investigating the involvement of additional cell adhesion pathway components downstream of GDF-15, SHP-1 was identified as a central mediator of GDF-15-related inhibition of T cell adhesion. SHP-1 is an intracellular tyrosine phosphatase known as a negative regulator of antigen-dependent activation and proliferation of T cells. Inhibition of SHP-1 resulted in abrogation of GDF-15’s inhibitory effect. The researchers confirmed that GDF-15 via SHP-1 inhibits the phosphorylation of ZAP-70, another intracellular tyrosine kinase involved in LFA-1 inside-out activation and T cell receptor signaling. These data connect SHP-1 as a downstream effector to the recently published GDF-15-mediated reduction of high-affinity LFA-1 conformation, leading to impaired endothelial adhesion and transmigration of T cells toward the tumor site. Poster Presentation Details Title: SHP-1 is a central mediator of GDF-15 mediated adhesion inhibition in T cells Presenter: Dr. Christine Schuberth-Wagner Abstract number: 1049 Date and time: Friday, Nov 3rd, 5:00-6:30pm PDT Poster Presentation on Visugromab/T-Cell Engager Combination The second data set supports the expansion of visugromab’s application to combinations with immune cell-engaging therapies, underlining its potential to be a critical component for treatment success in a broad range of anti-cancer regimens. The preclinical analyses investigated a new combination of visugromab with a bispecific T-cell engager (tebentafusp). Anti-tumor activity of bispecific T-cell engagers is dependent on infiltration of effector T cells into the tumor microenvironment. In vivo analyses in a mouse tumor model demonstrated that the combination with visugromab significantly increased the number of intratumoral T cells compared with tebentafusp alone. This indicates a direct positive impact of visugromab’s infiltration-enhancing activity on the anti-tumor activity of bispecific T-cell engaging treatments and provides a strong rationale to further investigate this therapeutic concept. Poster Presentation Details Title: GDF-15 neutralizing antibody visugromab increases intratumoral immune cell infiltration to support bispecific T-cell engagers Presenter: Dr. Christine Schuberth-Wagner Abstract number: 1196 Date and time: Saturday, Nov 4th, 7:00-8:30pm PDT CatalYm is investigating its GDF-15-neutralizing antibody visugromab in a broad Phase 2 clinical program, the GDFather (GDF-15 Antibody-mediaTed Human Effector Cell Relocation) trials, in combination with the anti-PD-1 inhibitor nivolumab in patients with advanced solid tumors. First interim data from the Phase 2 (NCT04725474) trial continue to demonstrate a very good safety and tolerability pro promising early responses in major cancer indications, including non-small cell lung cancer (NSCLC), bladder cancer and hepatocellular carcinoma (HCC). In addition, CatalYm recently announced an exploratory Phase 2 study, GDFather-NEO (NCT06059547), evaluating visugromab in combination with neoadjuvant immunotherapy in first-line muscle-invasive bladder cancer. About Visugromab (CTL-002) Visugromab is a monoclonal antibody that neutralizes the tumor-derived Growth Differentiation Factor-15 (GDF-15), a locally acting immunosuppressant fostering immunotherapy resistance. Neutralizing GDF-15 with visugromab reverses key cancer resistance mechanisms to reinstate an efficient anti-tumor response by reenabling immune cell activation and tumor infiltration. Visugromab has already demonstrated a good safety pro potent and durable anti-tumor efficacy in combination with anti-PD-1 treatment in advanced cancer patients The antibody is currently being investigated in ongoing Phase 2 studies in multiple solid tumor indications. About CatalYm CatalYm has identified GDF-15 as a key cancer therapy resistance mechanism and is developing a safe and efficacious immune therapy for solid tumors. GDF-15, an immunosuppressant important for feto-maternal tolerance, is hijacked by cancer cells to evade immune system attack. Visugromab, CatalYm’s lead antibody, has demonstrated durable anti-tumor efficacy with long-lasting objective responses in relapsed and refractory metastatic solid tumor patients in combination with anti-PD-1. CatalYm is now advancing to Phase 2b studies to confirm visugromab as a new class of cancer immunotherapy in a broad range of anti-cancer regimens.