A Randomized Phase 2 Study of Casdozokitug in Combination With Toripalimab Plus Bevacizumab in Participants With Unresectable and/or Locally Advanced or Metastatic Hepatocellular Carcinoma

The main goals of this study are to evaluate the safety and efficacy of casdozokitug in combination with toripalimab plus bevacizumab and to define a recommended dose for casdozokitug in combination with toripalimab plus bevacizumab.

Start Date20 Dec 2024

Sponsor / Collaborator

Coherus BioSciences, Inc.

NCT05359861

/ Active, not recruitingPhase 2

A Randomized Phase 2 Trial of Atezolizumab and Bevacizumab in Combination With SRF388 or Placebo in Patients With Untreated Locally Advanced or Metastatic Hepatocellular Carcinoma

This is a Phase 2 trial composed of an open label Lead-In followed by a Randomized Phase designed to evaluate the efficacy and safety of SRF388 in combination with atezolizumab plus bevacizumab compared to placebo (inactive substance) in combination with atezolizumab plus bevacizumab in patients with first-line advanced or metastatic HCC.

Start Date12 Apr 2022

Sponsor / Collaborator

Coherus BioSciences, Inc.

NCT04374877

/ RecruitingPhase 1

A Phase 1/1b Study of CHS-388 (Formerly Known as SRF388) in Patients With Advanced Solid Tumors

This is a Phase 1/1b, open-label, first-in-human, dose-escalation and expansion study of CHS-388, a monoclonal antibody that targets IL-27, as a monotherapy and in combination in patients with solid tumors.

Start Date22 Apr 2020

Sponsor / Collaborator

Coherus BioSciences, Inc.

[+1]

100 Clinical Results associated with Casdozokitug

100 Translational Medicine associated with Casdozokitug

100 Patents (Medical) associated with Casdozokitug

Literatures (Medical) associated with Casdozokitug

01 Aug 2023·International immunopharmacology

IL-27 enhances peripheral B cell glycolysis of rheumatoid arthritis patients via activating mTOR signaling.

Article

Author: Liu, Jiaqing ; Huang, Huina ; Zhao, Xiangge ; Qi, Jingjing ; Tang, Yawei ; Li, Xia

Our previous study found that increased serum IL-27 could promote rheumatoid arthritis (RA) B cell dysfunction via activating mTOR signaling pathway. This study aimed to explore the effects of IL-27 on B cell metabolism and clarify the mechanisms via which IL-27 enhancing glycolysis to induce B cells hyperactivation. Peripheral CD19⁺ B cells were purified from healthy controls (HC) and RA patients and then cultured with or without anti-CD40/CpG and glycolysis inhibitor 2-deoxy-D-glucose (2-DG) or mTOR inhibitor rapamycin. Furthermore, the isolated CD19⁺ B cells were treated by HC serum or RA serum in the presence and absence of recombinant human IL-27 or anti-IL-27 neutralizing antibodies or 2-DG or rapamycin. The B cell glycolysis level, proliferation, differentiation and inflammatory actions were detected by qPCR, flow cytometry or ELISA. We found that the glycolysis in RA B cells was increased significantly compared with HC B cells. Glycolysis inhibition downregulated the proliferation, differentiation, and inflammatory actions of RA B cells. RA serum and IL-27 promoted B cell glycolysis, which could be obviously rescued by anti-IL-27 antibodies or mTOR inhibitor rapamycin. Our results suggest that the enhanced cellular glycolysis of RA B cells induced by IL-27 may contribute to B cells hyperactivation through activating the mTOR signaling pathway.

01 Oct 2022·Cell reports

Structural basis of activation and antagonism of receptor signaling mediated by interleukin-27

Article

Author: Składanowska, Katarzyna ; Hunter, Christopher A ; Hua, Jing ; Logan, Derek T ; Soete, Arne ; Aldridge, Daniel ; Bazan, J Fernando ; Bloch, Yehudi ; White, Kerry F ; Welin, Martin ; Hill, Jonathan A ; Savvides, Savvas N ; Strand, Jamie ; Merceron, Romain ; Murphy, Casey ; Provost, Mathias

Interleukin-27 (IL-27) uniquely assembles p28 and EBI3 subunits to a heterodimeric cytokine that signals via IL-27Rα and gp130. To provide the structural framework for receptor activation by IL-27 and its emerging therapeutic targeting, we report here crystal structures of mouse IL-27 in complex with IL-27Rα and of human IL-27 in complex with SRF388, a monoclonal antibody undergoing clinical trials with oncology indications. One face of the helical p28 subunit interacts with EBI3, while the opposite face nestles into the interdomain elbow of IL-27Rα to juxtapose IL-27Rα to EBI3. This orients IL-27Rα for paired signaling with gp130, which only uses its immunoglobulin domain to bind to IL-27. Such a signaling complex is distinct from those mediated by IL-12 and IL-23. The SRF388 binding epitope on IL-27 overlaps with the IL-27Rα interaction site explaining its potent antagonistic properties. Collectively, our findings will facilitate the mechanistic interrogation, engineering, and therapeutic targeting of IL-27.

01 Feb 2019·HaematologicaQ1 · MEDICINE

The TLR7 ligand R848 prevents mouse graft-versus-host disease and cooperates with anti-interleukin-27 antibody for maximal protection and regulatory T-cell upregulation

Q1 · MEDICINE

Article

Author: Dumoutier, Laure ; Van Snick, Jacques ; Coutelier, Jean-Paul ; Uyttenhove, Catherine ; Gaignage, Mélanie ; Marillier, Reece G ; Cochez, Perrine M

In spite of considerable therapeutic progress, acute graft-versus-host disease still limits allogeneic hematopoietic cell transplantation. We recently reported that mouse infection with nidovirus lactate dehydrogenase elevating virus impairs disease in non-conditioned B6D2F1 recipients of parental B6 spleen cells. As this virus activates TLR7, we tested a pharmacological TLR7 ligand, R848, in this model and observed complete survival if donor and recipients were treated before transplantation. Mixed lymphocyte culture performed 48 h after R848-treatment of normal mice demonstrated that both T-cell allo-responsiveness and antigen presentation by CD11b⁺ and CD8α⁺ dendritic cells were inhibited. These inhibitions were dependent on IFNAR-1 signaling. In the B6 to B6D2F1 transplantation model, R848 decelerated, but did not abrogate, donor T-cell implantation and activation. However, it decreased interferon-gamma, tumor necrosis factor-alpha and interleukin-27 while upregulating active transforming growth factor-beta 1 plasma levels. In addition, donor and recipient Foxp3⁺ regulatory T-cell numbers were increased in recipient mice and their elimination compromised disease prevention. R848 also strongly improved survival of lethally irradiated BALB/c recipients of B6 hematopoietic cells and this also correlated with an upregulation of CD4 and CD8 Foxp3⁺ regulatory T cells that could be further increased by inhibition of interleukin-27. The combination of anti-interleukin-27p28 mono -clonal antibody and R848 showed strong synergy in preventing disease in the B6 to B6D2F1 transplantation model when recipients were sublethally irradiated and this also correlated with upregulation of regulatory T cells. We conclude that R848 modulates multiple aspects of graft-versus-host disease and offers potential for safe allogeneic bone marrow transplantation that can be further optimized by inhibition of interleukin-27.

News (Medical) associated with Casdozokitug

01 Apr 2025

·www.globenewswire.com

Coherus Announces Repurchase of Approximately $170 Million of Convertible Notes

– Remaining $60 Million of outstanding convertible notes to be repurchased post-close of pending UDENYCA divestiture – REDWOOD CITY, Calif., April 01, 2025 (GLOBE NEWSWIRE) -- Coherus BioSciences, Inc. (“Coherus” or the “Company,” NASDAQ: CHRS) announced today that it has entered into privately negotiated transactions (the “Repurchases”) with certain holders (the “Holders”) of its 1.500% Convertible Senior Subordinated Notes due 2026 (the “Convertible Notes”), pursuant to which the Company agreed to repurchase approximately $170 million aggregate principal amount of the Convertible Notes from such holders at a cash repurchase price equal to 100% of their principal amount, together with the accrued and unpaid interest to, but excluding, the date of repurchase. The Repurchases are conditioned upon, among other things, the closing of the previously announced divestiture of the UDENYCA (pegfilgrastim-cbqv) franchise pursuant to that certain asset purchase agreement (the “Agreement”), dated as of December 2, 2024 between the Company and Intas Pharmaceuticals Ltd. (“Intas”), a limited company incorporated in India (the “Transaction”). Following the closing of the Repurchases, approximately $60 million aggregate principal amount of Convertible Notes will remain outstanding. Following the closing of the Transaction, Coherus intends to conduct a repurchase offer for such remaining Convertible Notes pursuant to the Fundamental Change Repurchase Right (as defined in the indenture, dated as of April 17, 2020 (the “Indenture”), between the Company and U.S. Bank Trust Company, National Association, as trustee (the “Trustee”)) at a cash repurchase price equal to 100% of their principal amount, together with the accrued and unpaid interest to, but excluding, the date of repurchase. Coherus also announced today that the Holders party to the Repurchases, which constitute a majority of the aggregate principal amount of the outstanding Convertible Notes, have agreed to provide their consent (the “Requisite Consents”) to adopt certain proposed amendments (the “Amendments”) to the Indenture. In connection with the Requisite Consents, the Company and the Trustee will execute a supplemental indenture (the “Supplemental Indenture”) to the Indenture effecting the Amendments. The Amendments will modify the Indenture to permit the proposed transaction for the divestiture of UDENYCA. About Coherus BioSciences Coherus is a fully integrated commercial-stage innovative oncology company with an approved next-generation PD-1 inhibitor, LOQTORZI® (toripalimab-tpzi), with growing revenues and a promising pipeline that includes two mid-stage clinical candidates targeting liver, lung, head & neck, and other cancers. Our strategy is to grow sales of LOQTORZI in nasopharyngeal carcinoma and advance the development of new indications for toripalimab in combination with both our pipeline candidates as well as our partners’, driving multiple development and sales synergies from proprietary combinations. Coherus’ immuno-oncology pipeline includes multiple antibody immunotherapy candidates focused on enhancing the innate and adaptive immune responses to enable a robust antitumor immunologic response and enhance outcomes for patients with cancer. Casdozokitug is a novel IL-27 antagonistic antibody currently being evaluated in three ongoing clinical studies: a Phase 1/2 study in advanced solid tumors including combination with toripalimab in NSCLC, a Phase 2 study in HCC, and a randomized Phase 2 study in HCC evaluating casdozokitug in combination with toripalimab and bevacizumab. CHS-114 is a highly selective, competitively positioned, cytolytic anti-CCR8 antibody currently in a Phase 1 study in patients with advanced solid tumors, including HNSCC and gastric cancer. Coherus markets LOQTORZI, a novel next-generation PD-1 inhibitor, and UDENYCA® (pegfilgrastim-cbqv), a biosimilar of Neulasta. In December 2024, Coherus announced the planned divestiture of its UDENYCA franchise. The transaction is expected to close early in the second quarter of 2025. Neulasta® is a registered trademark of Amgen, Inc. Forward-Looking Statements The statements in this press release include express or implied forward-looking statements within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934 about the Repurchases, the Requisite Consents, the Supplemental Indenture and the proposed transaction between the Company and Intas that involve risks and uncertainties relating to future events and the future performance of the Company. Forward-looking statements relate to expectations, beliefs, projections, future plans and strategies, anticipated events or trends and similar expressions concerning matters that are not historical facts. Words such as “will,” “could,” “would,” “should,” “expect,” “plan,” “anticipate,” “intend,” “believe,” “estimate,” “predict,” “project,” “potential,” “continue,” “future,” “opportunity,” “likely,” “target,” variations of such words, and similar expressions or negatives of these words are intended to identify such forward-looking statements, although not all forward-looking statements contain these identifying words. You can also identify forward-looking statements by discussions of strategy, plans or intentions. Examples of such forward-looking statements include, but are not limited to, express or implied statements regarding: Coherus’ business, the Agreement and related matters, including, but not limited to, the consummation of the Repurchases, the Requisite Consents and the Supplemental Indenture, the ability to satisfy the closing conditions to consummate the proposed transaction at all or in the estimated time frame; prospective performance and opportunities with respect to the Company and its pipeline; statements about revenue or sales growth; statements about development and sales synergies; the ability of the Company’s product candidates to enhance outcomes for cancer patients; statements about the potential uses of proceeds from the proposed divestiture transaction including with respect to the repurchase offer for remaining Convertible Notes following the closing of the divestiture transaction; statements about the Company’s ability to repay its indebtedness in the future and the assumptions underlying or relating to such statements. These forward-looking statements are based on the Company’s current plans, estimates and projections. By their very nature, forward-looking statements involve inherent risks and uncertainties, both general and specific, assumptions and changes in circumstances, many of which are beyond the control of the Company. A number of important factors, including those described in this press release, could cause actual results to differ materially from those contemplated in any forward-looking statements. Factors that may affect future results and may cause these forward-looking statements to be inaccurate include, without limitation: uncertainties as to the timing for completion of the proposed transaction, including the Repurchases, the Requisite Consents and the Supplemental Indenture; uncertainties as to the Company’s ability to satisfy the conditions necessary to consummate the proposed UDENYCA divestiture; the possibility that competing offers will be made by third parties; the occurrence of any event, change or other circumstance that may give rise to a right of one or both of Intas and the Company to terminate the Agreement; the possibility that the proposed transaction may not be completed in the time frame expected by the Company or at all; the risk that the proposed transaction disrupts the Company’s current plans and operations or diverts the attention of the Company’s management or employees from ongoing business operations; the effects of the proposed transaction on relationships with the Company’s employees, suppliers, business or collaboration partners or governmental entities, or other third parties as a result of the proposed transaction; the ability to retain and hire key personnel; significant or unexpected costs, charges or expenses resulting from the proposed transaction; the potential impact of unforeseen liabilities, future capital expenditures, revenues, costs, expenses, earnings, economic performance, indebtedness, financial condition and losses on the future prospects, business and management strategies for the management, expansion and growth of the Company after the consummation of the proposed transaction; potential negative effects related to this announcement or the consummation of the proposed transaction on the market price of the Company’s common stock and/or the Company’s operating or financial results; and the nature, cost and outcome of any litigation and other legal proceedings, including any legal proceedings related to the proposed UDENYCA divestiture transaction. While the foregoing list of factors presented here is considered representative, no list should be considered to be a complete statement of all potential risks and uncertainties. There can be no assurance that the transaction described above will in fact be consummated in the manner described or at all. For a further discussion of these and other factors that could cause the Company’s future results to differ materially from any forward-looking statements see the section entitled “Risk Factors” in the Company’s Annual Report on Form 10-K for the year ended December 31, 2024, filed with the Securities and Exchange Commission (“SEC”) on March 17, 2025, as updated by the Company’s subsequent periodic reports filed with the SEC and in other documents the Company files with the SEC, including the definitive proxy statement of the Company relating to the proposed transaction for the divestiture of UDENYCA filed with the SEC on January 28, 2025. Any forward-looking statements speak only as of the date of this press release and are made based on the current good faith beliefs and judgments of the Company’s management, and the reader is cautioned not to rely on any forward-looking statements made by the Company. Unless required by law, the Company is not under any duty and undertakes no obligation to publicly update or revise any forward-looking statement to reflect changes in underlying assumptions or factors, of new information, data or methods, future events or other changes UDENYCA® 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. No Offer or Solicitation This communication is not intended to and shall not constitute an offer to buy or sell or the solicitation of an offer to buy or sell any securities, or a solicitation of any vote or approval, nor shall there be any sale of securities in any jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such jurisdiction. No offering of securities shall be made, except by means of a prospectus meeting the requirements of Section 10 of the U.S. Securities Act of 1933, as amended. Additional Information and Where to Find It In connection with the proposed divestiture of UDENYCA, the Company filed with the SEC a definitive proxy statement on Schedule 14A on January 28, 2025, and it may also file other documents regarding the proposed transaction with the SEC. Promptly after filing its definitive proxy statement with the SEC, the Company started the process of mailing the definitive proxy statement and a proxy card to each stockholder entitled to vote at the special meeting relating to the proposed transaction. INVESTORS AND SECURITY HOLDERS ARE URGED TO READ CAREFULLY THE PROXY STATEMENT AND OTHER RELEVANT DOCUMENTS FILED OR TO BE FILED WITH THE SEC, AS WELL AS ANY AMENDMENTS OR SUPPLEMENTS THERETO AND ANY DOCUMENTS INCORPORATED BY REFERENCE THEREIN, IN THEIR ENTIRETY IF AND WHEN THEY BECOME AVAILABLE BECAUSE THEY CONTAIN OR WILL CONTAIN IMPORTANT INFORMATION ABOUT THE PROPOSED TRANSACTION, RELATED MATTERS AND THE PARTIES TO THE PROPOSED TRANSACTION. You may obtain a free copy of the proxy statement and other relevant documents (if and when they become available) that are or will be filed with the SEC for free at the SEC’s website at www.sec.gov. Copies of the documents filed with the SEC by the Company will be available free of charge on the Company’s website at https://investors.coherus.com/sec-filings or by contacting the Company’s Investor Relations Department at IR@coherus.com. Coherus BioSciences Contact Information: For investors:Jodi SieversVP, Investor Relations & Corporate CommunicationsIR@coherus.com

Phase 2ImmunotherapyPhase 1Acquisition

23 Jan 2025

·pipelinereview.com

Coherus Presents Final Phase 2 Clinical Casdozokitug Combination Data in Patients with Metastatic Hepatocellular Carcinoma at ASCO-GI 2025

– Casdozokitug, in combination with atezolizumab/bevacizumab, final data demonstrate durability of response and improvement in depth of response including a 17.2% complete response rate – – Antitumor activity was observed across both viral and non-viral etiologies – – Data support continued evaluation of casdozokitug with VEGF and PD-(L)1 blockade in HCC – – Randomized Phase 2 trial evaluating casdozokitug/bevacizumab/toripalimab now open for enrollment – REDWOOD CITY, CA, USA I January 22, 2025 I Coherus BioSciences, Inc. (Coherus, NASDAQ: CHRS), today announced final data from its Phase 2 open label clinical trial evaluating casdozokitug (casdozo), a selective and potent Interleukin (IL)-27-targeting antibody, in combination with atezolizumab (atezo) and bevacizumab (bev) in treatment naïve patients with unresectable locally advanced or metastatic hepatocellular carcinoma (HCC). These data are being presented at the 2025 ASCO Gastrointestinal Cancers Symposium taking place January 23-25, 2025, in San Francisco, California. These data showed an overall response rate of 38% compared to initially announced 27% 1 , and complete responses (CR) per RECIST v1.1 increased to 17.2% compared to previously announced 10.3% 2 and initial assessment of 0% 1 , demonstrating both an increase in ORR and a deepening of responses compared to previous datasets. Importantly, responses were seen in viral and nonviral disease, and toxicity was consistent with the known safety profiles of atezolizumab and bevacizumab, with no new safety signals identified. These data support continued evaluation of casdozo with other therapies, including a trial of casdozo/toripalimab (tori)/bev in HCC, which Coherus has now opened for enrollment. Casdozo is a first-in-class antibody, and the only clinical-stage immunomodulatory cytokine antagonist targeting IL-27, an immunoregulatory cytokine involved in suppressing anti-tumor immune responses and an important new target for cancer treatment. “The casdozo data in HCC demonstrate translation of the preclinical data in liver cancer to first-line HCC cancer patients with efficacy and a favorable safety profile. These data support the ongoing development of IL-27 as a promising novel target for advanced solid tumors,” said Rosh Dias, M.D., Coherus’ Chief Medical Officer. “We recently opened enrollment for our randomized, controlled, multinational Phase 2 trial of casdozo in combination with toripalimab, our anti-PD-1 antibody, plus bev. The combination of tori plus bev has demonstrated promising Phase 3 results in HCC 3 , and we believe the addition of casdozo may further enhance anti-tumor effects and advance our next-generation immuno-oncology combinations focused on overcoming immune suppression in the tumor microenvironment.” “The treatment landscape for liver cancer, particularly for patients who are not eligible for surgery or who are metastatic, has improved in recent years thanks to immunotherapy combinations. However, there is still a clear unmet need for novel treatment options that can further improve survival without added toxicity,” said Daneng Li, M.D., Associate Professor in the Department of Medical Oncology & Therapeutics Research and Co-Director, Liver Cancer Collaborative Program, City of Hope Comprehensive Cancer Center. “These final casdozo data continue to be encouraging and compare very favorably in the current treatment landscape, and speak to the potential for its novel anti-IL-27 mechanism to address these substantial unmet needs.” Results from Phase 2 trial evaluating casdozo/atezo/bev combination in HCC This open-label Phase 2 clinical trial evaluated casdozo in combination with atezo and bev in 30 treatment-naïve patients with unresectable locally advanced or metastatic HCC. Patients received casdozokitug 10 mg/kg IV q3w in combination with atezolizumab (1200 mg) and bevacizumab (15 mg/kg). The primary endpoint was safety and tolerability. Key secondary endpoints included PFS and ORR based on investigator review per RECIST v1.1 (primary) and mRECIST (secondary), as well as disease control rate (DCR). As of the data cutoff date of September 4, 2024: Triplet blockade of the IL-27, PD-(L)1 and VEGF inhibitors with casdozo/atezo/bev demonstrated an acceptable safety profile with promising antitumor activity in immunotherapy naïve HCC. These results support continued evaluation of casdozo with VEGF and PD-(L)1 blockade in HCC. Recent Launch of New Phase 2 trial evaluating casdozo in combination with bev and toripalimab Coherus has initiated a new randomized Phase 2 study ( NCT06679985 ) evaluating casdozo, in combination with bev and tori, Coherus’ next-generation anti-PD-1 monoclonal antibody, in participants with unresectable locally advanced or metastatic HCC. This randomized, parallel, open-label Phase 2 study is designed to evaluate the safety, efficacy, and Project Optimus 4 dosing of the triplet combination. The study is expected to enroll up to 72 patients, who will be randomized to receive one of two biologically active doses of casdozo with tori plus bev or tori plus bev without casdozo. ASCO-GI 2025 Presentation Details Title: Results from a phase 2 study of triplet blockade of the IL-27, PD-(L)1, and VEGF pathways with casdozokitug (casdozo, CHS-388) in combination with atezolizumab and bevacizumab in patients with unresectable, locally advanced or metastatic hepatocellular carcinoma (uHCC) Lead Author: Daneng Li, City of Hope National Comprehensive Cancer Center Abstract 605 : Poster Board #D6 Poster Session B: Cancers of the Pancreas, Small Bowel, and Hepatobiliary Tract Date and Time: Friday, January 24, 2025; 11:30am – 1:00pm PT About Hepatocellular Carcinoma Hepatobiliary cancers include a spectrum of invasive carcinomas arising in the liver (hepatocellular carcinoma; HCC), gall bladder, and bile ducts (collectively called biliary tract cancers). The most common type of primary liver cancer in adults is HCC (accounting for ~90%), which is the third leading cause of cancer-related deaths worldwide. According to the NCI Surveillance, Epidemiology and End Results Program (SEER), there will be an estimated 41,630 new cases and 29,840 deaths from liver and intrahepatic bile duct cancer in the US in 2024. 5 The U.S. 5-year relative survival rate for liver and intrahepatic bile duct cancer is 21.7%. 5 The liver cancer treatment pattern has changed in recent years with the emergence of immunotherapy combinations and will continue to evolve as more treatment options become available for these highly lethal cancers. About Casdozokitug Casdozokitug 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. 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). An ongoing trial is studying combinations with PD-(L)1 pathway blockade in NSCLC, and a planned clinical trial will study the triplet combination of IL-27, PD-(L)1, and VEGF pathway blockade in HCC. Casdozokitug has been granted Orphan Drug designation and Fast Track designation for the treatment of refractory hepatocellular carcinoma from the FDA. It is the first IL-27 antibody to enter the clinic. About Coherus BioSciences Coherus 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 is expected to be synergistic 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 antitumor immunologic response and enhance outcomes for patients with cancer. Casdozokitug is a novel IL-27 antagonistic 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, cytolytic anti-CCR8 antibody currently in a Phase 1 study in patients with advanced solid tumors, including HNSCC. CHS-1000 is a novel humanized Fc-modified IgG1 monoclonal antibody specifically targeting ILT4 (LILRB2). An IND for CHS-1000 was allowed to proceed by the FDA in the second quarter of 2024 and proceeding to the first-in-human clinical study is subject to further evaluation in Coherus’ portfolio prioritization process. Coherus markets LOQTORZI® (toripalimab-tpzi), a novel next-generation PD-1 inhibitor, and UDENYCA® (pegfilgrastim-cbqv), a biosimilar of Neulasta. In December 2024, Coherus announced the planned divestiture of its UDENYCA franchise. The transaction is expected to close by the end of the first quarter of 2025. References 1 Coherus to Acquire Surface Oncology (2023, June 16) [ Press Release ] 2 Daneng Li et al., JCO 42, 470-470(2024). 3 Yinghong S, et al. Oral presentation at: CSCO 2024; September 27, 2024; Xiamen, China. 4 Project Optimus: Reforming the dose optimization and dose selection paradigm in oncology 5 National Cancer Institute Cancer Stat Facts: Liver and Intrahepatic Bile Duct Cancer; retrieved December 17, 2024, from https://seer.cancer.gov/statfacts/html/livibd.html SOURCE: Coherus Biosciences

Clinical ResultPhase 2Orphan DrugImmunotherapyFast Track

18 Dec 2024

·www.globenewswire.com

Coherus to Present Final Phase 2 Casdozokitug Combination Data in Patients with Metastatic Hepatocellular Carcinoma at ASCO-GI 2025

- Randomized Phase 2 study initiated evaluating the combination of casdozokitug, toripalimab and bevacizumab in patients with liver cancer - REDWOOD CITY, Calif., Dec. 18, 2024 (GLOBE NEWSWIRE) -- Coherus BioSciences, Inc. (“Coherus,” NASDAQ: CHRS) today announced that an abstract highlighting final clinical and biomarker data from its Phase 2 clinical trial evaluating casdozokitug (casdozo), a selective and potent IL-27-antagonistic antibody, in combination with atezolizumab (atezo) and bevacizumab (bev) in treatment naïve patients with unresectable locally advanced or metastatic hepatocellular carcinoma (HCC), has been selected for a poster presentation at the upcoming 2025 ASCO GI Annual Meeting, being held January 23-25, 2025, in San Fransisco, CA. “Casdozo is a first-in-class antibody, and in oncology, is the first IL-27 cytokine antagonist to demonstrate monotherapy responses and immune activation with a safety profile that lends itself to combination,” said Rosh Dias, M.D., Coherus’ Chief Medical Officer. “We look forward to sharing the final data from this Phase 2 combination study of casdozo with standard of care with the medical community at the upcoming 2025 ASCO-GI annual meeting. We now have data across several tumor types for casdozo demonstrating clinical activity. We are particularly excited about HCC given the strong preclinical package for targeting IL-27 in liver cancer and now translation to the clinic.” Coherus has initiated a new randomized Phase 2 study (NCT06679985) evaluating casdozo, in combination with bevacizumab and toripalimab, Coherus’ next-generation anti-PD-1 monoclonal antibody, in participants with first-line HCC. This randomized, parallel, open-label Phase 2 study is designed to evaluate the safety, efficacy, and Project Optimus1 dosing of the triplet combination. The study is expected to enroll up to 72 patients, who will be randomized to receive one of two biologically active doses of casdozo with toripalimab plus bevacizumab or toripalimab plus bevacizumab without casdozo. “Advancing casdozo development in first-line HCC with a randomized Phase 2 combination study marks a significant milestone in our strategic path to progress our clinical pipeline, which is focused on overcoming immune suppression in the tumor microenvironment to extend survival and improve outcomes for patients and pursuing new indications for toripalimab in the U.S.,” continued Dr. Dias. “Casdozo has shown encouraging responses in the first line setting when added to the existing standard of care, atezolizumab and bevacizumab, and we’re excited to build upon these data with this new Phase 2 study evaluating casdozo in combination with toripalimab and bevacizumab.” In the Phase 3 HEPATORCH study, conducted by Junshi Biosciences, patients with advanced HCC treated with toripalimab combined with bevacizumab as a first-line therapy showed significantly better clinical efficacy than sorafenib monotherapy.2 HEPATORCH patients showed an objective response rate of 25.3% versus 6.1% in the sorafenib group, a median progression-free survival of 5.8 months, and a median overall survival of 20 months, compared to 4 and 14.5 months, respectively, for the sorafenib group.3 Toripalimab in combination with bevacizumab was well tolerated, with a toxicity profile consistent with the known toxicity profile of each monotherapy, with no new safety signals identified.3 The results of the HEPATORCH study support the clinical study of toripalimab in combination with bevacizumab as a new first-line treatment option for advanced HCC which, along with the results from the Phase 2 casdozo study reported to date, support pursuing a triple combination of casdozo with toripalimab plus bevacizumab in patients with advanced or metastatic HCC. ASCO-GI 2025 Presentation Details Title: Results from a phase 2 study of triplet blockade of the IL-27, PD-(L)1, and VEGF pathways with casdozokitug (casdozo, CHS-388) in combination with atezolizumab and bevacizumab in patients with unresectable, locally advanced or metastatic hepatocellular carcinoma (uHCC) Lead Author: Daneng Li, City of Hope National Comprehensive Cancer CenterAbstract #: 605Poster Session B: Cancers of the Pancreas, Small Bowel, and Hepatobiliary TractDate and Time: Friday, January 24, 2025; 11:30 a.m. – 1:00 p.m. PT Hepatobiliary cancers include a spectrum of invasive carcinomas arising in the liver (hepatocellular carcinoma; HCC), gall bladder, and bile ducts (collectively called biliary tract cancers). The most common type of primary liver cancer in adults is HCC (accounting for ~90%), which is the third leading cause of cancer-related deaths worldwide. According to the NCI Surveillance, Epidemiology and End Results Program (SEER), there will be an estimated 41,630 new cases and 29,840 deaths from liver and intrahepatic bile duct cancer in the US in 2024.4 The U.S. 5-year relative survival rate for liver and intrahepatic bile duct cancer is 21.7%.4 The liver cancer treatment pattern has changed in recent years with the emergence of immunotherapy combinations and will continue to evolve as more treatment options become available for these highly lethal cancers. About Coherus BioSciences Coherus 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 is expected to be synergistic with toripalimab and 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 antitumor immunologic response and enhance outcomes for patients with cancer, particularly patients underserved by current immunotherapy treatments. Casdozokitug is a novel IL-27 antagonistic antibody 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, cytolytic anti-CCR8 antibody currently in a Phase 1 study in patients with advanced solid tumors, including HNSCC. CHS-1000 is a novel humanized Fc-modified IgG1 monoclonal antibody specifically targeting ILT4 (LILRB2). An IND for CHS-1000 was allowed to proceed by the FDA in the second quarter of 2024 and proceeding to the first-in-human clinical study is subject to further evaluation in our portfolio prioritization process. Coherus markets LOQTORZI® (toripalimab-tpzi), a novel next-generation PD-1 inhibitor, and UDENYCA® (pegfilgrastim-cbqv), a biosimilar of Neulasta. In December 2024, Coherus announced that it entered into an agreement for the divestiture of the UDENYCA franchise. The proposed transaction is expected to close by the end of the first quarter of 2025. Neulasta® is a registered trademark of Amgen, 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’ expectations about identifying synergies between its I-O pipeline and its commercial operations and its I-O pipeline and toripalimab; future enrollment estimates for Coherus’ clinical studies; Coherus’ expectations that it will be able to demonstrate that its clinical pipeline candidates can extend patient survival; and the ability to satisfy the closing conditions to consummate the proposed transaction for the divestiture of the UDENYCA franchise at all or in the estimated time. 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 Coherus’ existing and potential collaboration partners; risks of Coherus’ reliance on third-parties; the risks and uncertainties related to manufacturing and supply of Coherus’ products, the risks and uncertainties of the regulatory approval process, including the speed of regulatory review and the timing of Coherus’ regulatory filings; uncertainties as to the timing for completion of the proposed transaction; uncertainties as to the Company’s ability to obtain the approval of its shareholders required to consummate the proposed transaction for the divestiture of UDENYCA; the possibility that competing offers will be made by third parties; the occurrence of any event, change or other circumstance that may give rise to a right of one or both parties to terminate the agreement to divest UDENYCA; the possibility that the proposed transaction for the divestiture of UDENYCA may not be completed in the time frame expected by the Company or at all, including due to the possibility that a governmental entity may prohibit, delay, or refuse to grant approval, if required, for the consummation of the proposed transaction to divest UDENYCA (or only grant approval subject to adverse conditions or limitations). All forward-looking statements contained in this press release speak only as of the date of this press release. Unless required by law, the Company is not under any duty and undertakes no obligation to publicly update or revise any forward-looking statement to reflect changes in underlying assumptions or factors, of new information, data or methods, future events or other changes. 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 September 30, 2024 filed with the Securities and Exchange Commission on November 6, 2024, including the section therein captioned “Risk Factors” and in other documents Coherus files with the Securities and Exchange Commission including, when available, the proxy statement of the Company relating to the proposed transaction for the divestiture of UDENYCA. UDENYCA® 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:Jodi SieversVP, Investor Relations & Corporate CommunicationsIR@coherus.com For Media:Argot Partners(212) 600-1902coherus@argotpartners.com 1Project Optimus: Reforming the dose optimization and dose selection paradigm in oncology 2Shanghai Junshi Biosciences Co., Ltd (2024, June 11) Junshi Biosciences Announces Phase 3 Study of Toripalimab Combined with Bevacizumab for the First-line Treatment of Advanced Hepatocellular Carcinoma Meets Primary Endpoint 3FAN, J. (2024) HEPATORCH: A randomized, open-label, multicenter, phase III clinical study of the safety and efficacy of toripalimab combined with bevacizumab versus sorafenib as first-line treatment for advanced hepatocellular carcinoma presented at the 2024 Annual Meeting of Chinese Society of Clinical Oncology 4National Cancer Institute Cancer Stat Facts: Liver and Intrahepatic Bile Duct Cancer; retrieved December 17, 2024, from https://seer.cancer.gov/statfacts/html/livibd.html

Phase 2Clinical ResultImmunotherapyPhase 3ASCO

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R&D Status

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Indication	Highest Phase	Country/Location	Organization	Date
Non-Small Cell Lung Cancer	Phase 2	United States	Surface Oncology, Inc.	14 Apr 2022
Metastatic hepatocellular carcinoma	Phase 2	United States	Coherus BioSciences, Inc.	12 Apr 2022
Metastatic hepatocellular carcinoma	Phase 2	Australia	Coherus BioSciences, Inc.	12 Apr 2022
Metastatic hepatocellular carcinoma	Phase 2	South Korea	Coherus BioSciences, Inc.	12 Apr 2022
Metastatic hepatocellular carcinoma	Phase 2	Taiwan Province	Coherus BioSciences, Inc.	12 Apr 2022
Locally Advanced Malignant Solid Neoplasm	Phase 1	United States	Coherus BioSciences, Inc.	22 Apr 2020
Locally Advanced Malignant Solid Neoplasm	Phase 1	Singapore	Coherus BioSciences, Inc.	22 Apr 2020
metastatic non-small cell lung cancer	Phase 1	United States	Coherus BioSciences, Inc.	22 Apr 2020
metastatic non-small cell lung cancer	Phase 1	Singapore	Coherus BioSciences, Inc.	22 Apr 2020
Renal Cell Carcinoma	Phase 1	United States	Coherus BioSciences, Inc.	22 Apr 2020

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT05359861 (ASCO_GI2025) Manual	Phase 2	Hepatocellular Carcinoma	30	Casdozo 10 mg/kg + Atezolizumab 1200 mg + Bevacizumab 15 mg/kg (RECIST1.1)	msztgzfatb(wzcsbpkoki) = stvfovdtud kmupsteydr (xppeehlssn ) View more	Positive	23 Jan 2025
NCT05359861 (ASCO_GI2025) Manual	Phase 2	Hepatocellular Carcinoma	30	Casdozo 10 mg/kg + Atezolizumab 1200 mgAtezolizumab 1200 mg + Bevacizumab 15 mg/kg (mRECIST)	wbvhvmjhjp(gqrehcnjcp) = hjlkqzrfpc gvcaxtriug (pxaiesmuvn ) View more	Positive	23 Jan 2025
NCT04374877 (ESMO_IO2024) Manual	Phase 1	Non-Small Cell Lung Cancer	45	Casdozokitug (casdozo, CHS-388) 10 mg/kg IV q4 wks	iscqkrrsux(cjyusyvirx) = uddswoaiez uciofxxubk (ehicjwhsvq ) View more	Positive	12 Dec 2024
NCT05359861 (ASCO_GI2024) Manual	Phase 2	Hepatocellular Carcinoma First line	30	Casdozokitug+atezolizumab+bevacizumab	ygyzdktfiu(mqhtajfgor) = jrdchsnkyb tuzyxqmsyk (nrkobteigf ) View more	Positive	18 Jan 2024
NCT04374877 (GlobeNewswire) Manual	Phase 1/2	Solid tumor PD-L1	-	Casdozokitug (PD-L1 negative or low, squamous NSCLC)	dvmvpnhlsf(npbbxqckgf) = uhgpkeixqh oksysyaept (gsbzumsteb )	Positive	06 Dec 2023
NCT04374877 (GlobeNewswire) Manual	Phase 1/2	Solid tumor PD-L1	-	Casdozokitug (adenocarcinoma)	xlmtgxqdvt(wxqnjqhdmh) = wvnonfbufr htqdptnlci (vvkspxrffr )	Positive	06 Dec 2023
NCT04374877 (ASCO2022) Manual	Phase 1	HR-positive/HER2-low Solid Tumors	29	SRF388	ocbqkgsysa(lgcpfqdvfi) = lsbkontudb jjxhcwavhx (vuexgozjxf ) View more	Positive	02 Jun 2022
NCT04374877 (ASCO2021)	Phase 1	HR-positive/HER2-low Solid Tumors	12	SRF388	degstjoviw(qwcojzcfli) = nwciirasdd bgtfnglvcl (mhbatuqezi )	-	28 May 2021

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