On April 8, 2024 Imugene Limited (ASX: IMU), a clinical stage immuno-oncology company, reported poster presentations featuring its CF33 oncolytic virotherapy VAXINIA and B cell immunotherapy HER-Vaxx at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 5-10 April 2024, in San Diego, CA.

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Daneng Li, M.D., a City of Hope associate professor in the Department of Medical Oncology & Therapeutics Research commented, "The results show that our novel oncolytic virus — both alone or in combination with immunotherapy — has the ability to control various cancer types previously resistant to other treatment options, and these early results provide patients with hope of a new treatment option for cancers refractory to standard treatment."

Imugene Managing Director & CEO Leslie Chong said: "Preliminary data from the MAST trial demonstrates encouraging anti-tumour activity with our oncolytic virus CF33-hNIS (VAXINIA). Notably, one patient with cholangiocarcinoma, or biliary tract cancer, achieved an immunological complete response (CR), meaning the disappearance of all signs of their cancer after treatment with VAXINIA, with no known recurrence after one year. These encouraging results warrant further investigation in patients will biliary tract cancer and other cancers. In addition, further analysis of the T cell repertoire reveals that T cell diversity may serve a predictive biomarker, which can be used to prospectively identify appropriate patients for treatment."

Details on the poster presentations are below:

Presentation Title: Oncolytic virus CF33-hNIS for the treatment of advanced cancer
Abstract Presentation Number: CT182
Session Date and Time: Tuesday April 9, 2024, 9:00 AM – 12:30 PM PT
Session Title: First-in-Human Phase I Clinical Trials 2
Presenter: Daneng Li, MD
Highlights include:

At the data cut-off of 19 December 2023, there were 31 efficacy-evaluable patients in the MAST study. In the intratumoural (IT) cohorts, 7 of 16 (44%) injected lesions had a reduction in tumour burden and 3 lesions were completely eradicated.Three of the IT treated patients had an objective response: 1 complete response by iRECIST in a patient with cholangiocarcinoma and 2 partial responses by RECIST inpatients with melanoma. In the intravenous (IV) cohorts, 9 of 17 (53%) patients achieved stable disease as their best response. Patients who received prior checkpoint blockade therapy derived clinical benefit with and without pembrolizumab. Viral replication, assessed by SPECT, was higher in patients who had a reduction in tumour burden.
Patients with a higher level of T cell diversity in peripheral blood (pre-treatment)respond better to VAXINIA therapy, consistent with the known mechanism of action of oncolytic virotherapies and their ability to promote an anti-tumour T cell response.
Both IT- and IV-treated patients have promising immunological changes in on-treatment tumour biopsies (including increases in cancer fighting CD8 T cells and PD-L1 expression) indicated that VAXINIA can transform the tumour microenvironment.
Several patients have had prior treatment with checkpoint blockade, including astable disease cholangiocarcinoma patient and two melanoma partial response patients. This suggests that VAXINIA +/- checkpoint inhibitor combination could be used in the checkpoint therapy refractory setting, which is seeing a growing and unmet market in oncology, by altering the tumour microenvironment.

Presentation Title: Frontline vaccination with the B-cell peptide compound HER-Vaxx (IMU-131), combined with standard-of-care chemotherapy induces high levels of HER2-specific antibodies mediating ADCC and intracellular phosphorylation inhibition resulting in overall survival benefit in patients with HER2+ metastatic or advanced gastric/GEJ adenocarcinoma – Final results from Phase II/HERIZON study
Poster Number: CT215
Session Date and Time: Tuesday April 9, 2024, 9:00 AM – 12:30 PM PT
Session Title: Phase II Clinical Trials 1
Presenter: Joshua Tobias Ph.D.
Highlights include:

HER-Vaxx treatment produced robust anti-HER2-IgG and IgG1 antibody response (p<0.001).
HER-Vaxx induced HER2-specific antibodies able to mediate antibody-dependent cell cytotoxicity (ADCC) and inhibit intracellular HER2 phosphorylation and correlated with tumour reduction.
The HER-Vaxx induced HER2-specific antibodies demonstrate a similar mechanism of action to HERCEPTIN validating B cell immunotherapy as an alternative anti-cancer agent to monoclonal antibodies.
About the MAST Trial
The multicenter Phase 1 MAST trial commenced by delivering a low dose of VAXINIA to patients with metastatic or advanced solid tumours who have had at least two prior lines of standard of care treatment. The City of Hope-developed oncolytic virus has been shown to shrink colon, lung, breast, ovarian and pancreatic cancer tumours in preclinical laboratory and animal models¹. Overall, the study aims to recruit cancer patients across approximately 10 trial sites in the United States and Australia.
The clinical trial is titled "A Phase I, Dose Escalation Safety and Tolerability Study of VAXINIA (CF33- hNIS), Administered Intratumorally or Intravenously as a Monotherapy or in Combination with Pembrolizumab in Adult Patients with Metastatic or Advanced Solid Tumours (MAST)." The trial commenced in May 2022 and is anticipated to run for approximately 24 months while being funded from existing budgets and resources. Full study details can also be found on clinicaltrials.gov under study ID: NCT05346484.

On April 7, 2024 Shanghai Junshi Biosciences Co., Ltd ("Junshi Biosciences", HKEX: 1877; SSE: 688180), a leading innovation-driven biopharmaceutical company dedicated to the discovery, development, and commercialization of novel therapies, reported that the National Medical Products Administration ("NMPA") has approved the supplemental new drug application ("sNDA") for toripalimab (product code: JS001) in combination with axitinib for the first-line treatment of patients with medium to high risk unresectable or metastatic renal cell carcinoma ("RCC") (Press release, Shanghai Junshi Bioscience, APR 7, 2024, View Source [SID1234656135]). This is the first approved immunotherapy for renal carcinoma in China.

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Renal carcinoma is the third most common malignancy of the urinary system globally, and RCC accounts for 80%~90% of all cases of renal carcinoma. There were approximately 77,000 new cases of and 46,000 deaths due to renal carcinoma in China in 2022. Distant metastasis occurred in about one-third of renal carcinoma patients at initial diagnosis, and in 20%-50% of localized patients after nephrectomy. According to the risk classification of the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC), the median overall survival ("OS") of patients with low, medium and high risk metastatic RCC receiving anti-vascular targeted treatment were 35.3, 16.6 and 5.4 months, respectively. Therefore, compared to low-risk patients, the clinical needs for new treatment options are more urgent for patients with medium and high risk advanced RCC.

The approval of the sNDA is mainly based on data from the RENOTORCH study (NCT04394975), a multi-center, randomized, open-label, active-controlled Phase 3 clinical study led by principal investigators Professor Jun GUO from Peking University Cancer Hospital and Professor Yiran HUANG from Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine. The study was conducted across 47 medical centers, and represents the first pivotal Phase 3 clinical study of immunotherapy for patients with advanced RCC in China.

A total of 421 randomized patients with medium to high risk unresectable or metastatic RCC were enrolled in the study and randomly assigned in a 1:1 ratio to receive toripalimab in combination with axitinib (n=210) or sunitinib alone (n=211). The primary endpoint is progression free survival ("PFS") as assessed by the Independent Review Committee ("IRC"), and secondary endpoints include PFS as assessed by investigators, objective response rate ("ORR") as assessed by IRC or investigators, duration of response ("DoR"), disease control rate (DCR), OS, safety profile, etc.

Previously, the study results of RENOTORCH made its debut at the Proffered Paper Session of the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) congress 2023. The full text was simultaneously published in Annals of Oncology, the official journal of ESMO (Free ESMO Whitepaper). The study data showed that, based on the assessment results of IRC, compared with sunitinib monotherapy, toripalimab in combination with axitinib for the treatment significantly prolonged the PFS of patients by nearly twofold (median PFS: 18.0 vs. 9.8 months, P=0.0028), and the risk of disease progression or death was reduced by 35% (hazard ratio [HR]=0.65; 95% CI: 0.49, 0.86). In addition, the ORR was higher (56.7% vs. 30.8%, P<0.0001) and the DoR was longer (median DoR: not reached vs 16.7 months; HR=0.61) in the toripalimab group. The OS of the toripalimab group also showed a clear trend of benefit (median OS: not reached vs 26.8 months), and the risk of death was reduced by 39% (HR=0.61; 95%CI: 0.40, 0.92). In terms of safety, toripalimab in combination with axitinib demonstrated a favorable safety and tolerability profile, and no new safety signals were observed.

"From a global perspective, targeted therapy in combination with immunotherapy has become the standard treatment approach for advanced RCC," said Professor Jun GUO from Peking University Cancer Hospital. "However, no such treaments have been approved in China. The approval of toripalimab’s new indications opens a new chapter in combined targeted therapy and immunotherapy in China, and it will transform current clinical practices for advanced RCC and introduce new treatment options for medium to high-risk patients!"

"The treatment methods for advanced RCC are limited, especially for medium to high risk patients, who often face suboptimal prognoses," said Professor Yiran HUANG from Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine "The approval of toripalimab combined with axitinib addresses the gap in first-line immunotherapy for renal cancer in China. Compared to targeted monotherapy, toripalimab combined with targeted therapy will significantly improve patients’ PFS, offering promising prospects for many advanced RCC patients in China."

"Thank you to all medical professionals, patients, and R&D personnel involved in the RENOTORCH study for their contributions," said Dr. Jianjun ZOU, CEO of Junshi Biosciences. "Their dedication has led to a pioneering breakthrough in renal cancer, first of its kind in China! Junshi Biosciences will remain committed to addressing domestic clinical needs and continue investing in research and development to help patients live longer and better!"

On April 7, 2024, ImmuneOnco Biopharmaceuticals (Shanghai) Co., Ltd. reported that five innovative drug studies were accepted by the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in 2024, in which, they will be reported to global attendees in the form of oral presentations, posters and online publications (Press release, ImmuneOnco Biopharma, APR 7, 2024, View Source [SID1234655698]). It covers the latest clinical progress of IMM01(SIRP-IGG1 Fc), IMM0306 (CD47xCD20 mAb-Trap) and IMM2510 (VEGFxPD-L1 mAb-Trap).

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Two innovative clinical phase II studies of IMM01 were included in the oral reports (IMM01 combined with Tirelizumab for cHL indications after previous PD1 antibody treatment failure, and IMM01 combined with azacitide for high-risk MDS indications for initial treatment). A preliminary phase I clinical study of IMM0306 in the treatment of relapsed/refractory CD20-positive B-cell non-Hodgkin lymphoma (B-NHL) is presented in the form of poster. The results of the other two studies were presented in the form of online publication (the clinical phase Ib study of IMM0306 combined with lenalidomide in the treatment of relapsed/refractory CD20-positive B-cell non-Hodgkin lymphoma (B-NHL), and the clinical phase I dose-climbing study of lMM2510 monotherapy in the treatment of advanced solid tumors).

Founder and chairman of ImmuneOnco Dr. Tian, Wenzhi said:

"The findings we will present at ASCO (Free ASCO Whitepaper) 2024 will help inform the industry about the latest clinical development data for IMM01, IMM0306, and IMM2510." IMM01 is the first SIRP-α-FC fusion protein to enter the clinical stage in China being developed to use in combination with other drugs to treat a variety of blood tumors and solid tumors. Based on the initial effectiveness and good safety in clinical trials of monotherapy, as well as the clinical research data of IMM01 in clinical phase II treatment of cHL and MDS patients presented at the ASCO (Free ASCO Whitepaper) annual meeting, it will again prove that the differentiated molecular design of IMM01 perfectly solves the clinical safety problems commonly faced by CD47 antibody drug candidates. Our IMM01 has great potential to become the world’s first approved CD47-targeting drug. IMM0306 is another CD47-targeted macromolecule that has shown encouraging efficacy and a good safety profile in Phase I clinical studies in relapsed or refractory B-cell lymphomas. The Phase II clinical study of IMM0306 combined with lenalidomide is rapidly progressing, and the initial clinical performance is quite exciting. We believe that the differentiated molecular design of CD47-targeted drugs will be a key determinant of success in clinical development. IMM2510 is a bispecific molecule targeting VEGF and PD-L1, and has shown positive therapeutic signals against advanced non-small cell lung cancer (adenocarcinoma, squamous cell carcinoma) and thymic carcinoma. We are pleased to have the opportunity to share these data with our oncology colleagues and look forward to further releases of clinical data from IMM01, IMM0306, and IMM2510."

Chief Medical Officer/Senior Vice President of ImmuneOnco Dr. Lu, Qiying said:

"Following the preliminary clinical phase II data disclosed in ASH (Free ASH Whitepaper) last year, the results of two clinical phase II studies on IMM01 products were recognized and affirmed by the academic community at ASCO (Free ASCO Whitepaper) this year, and were accepted as oral reports by ASCO (Free ASCO Whitepaper) 2024; In addition, one research result of IMM0306 was displayed as a poster, and two research results were published online (clinical phase Ib results of IMM0306 combined with LEN and clinical phase I results of IMM2510). IMM01 is the company’s key product and one of the important cornerstones of our company in the field of tumor immunotherapy. In terms of clinical development layout of IMM01 products, we have carried out a differentiated tactics. For newly treated CMML patients, IMM01-02 is currently a prospective clinical study with the largest sample size for this rare tumor to meet the unmet medical needs. In view of the unmet medical needs of cHL after previous PD-1 failure, our combined treatment model can overcome the drug resistance of previous PD1 antibody therapy, and reflects the advantages of chemotherapy therapy, avoiding the long-term toxicity brought by chemotherapy drugs and bringing long-term quality of life to patients. Encouraging efficacy and good tolerability have been observed in initially treated high-risk MDS patients, initially treated CMML patients, and cHL patients after previous PD-1 antibody therapy failure. As one of the company’s key products, IMM0306 monotherapy was observed in a number of indications, outstanding initial efficacy (including FL and MZL mainly inert lymphoma and the most common clinical aggressive lymphoma DLBCL), indicating that this product has broad clinical development prospects. IMM2510 showed initial positive therapeutic signals in relapsed and refractory non-small cell lung cancer (adenocarcinoma, squamous cell carcinoma) and thymus cancer in the climbing study. In particular, one patient with lung squamous cell carcinoma obtained significant tumor shrinkage (PR) after the failure of PD-1 antibody therapy and combination chemotherapy, and the PR lasted more than 11 months. It has been receiving the investigational drug for more than 20 months and the treatment is still undergoing. In light of unmet clinical needs, we plan to further develop a single agent and a combination of different treatment modalities for multiple indications to explore efficacy in multiple solid tumors, including non-small cell lung cancer, triple negative breast cancer, and liver cancer in addition to soft tissue sarcomas. We look forward to rapidly advancing the clinical development of IMM01, IMM0306 and IMM2510 products, bringing new treatment options for the treatment of cancer patients and addressing unmet clinical needs."

On April 7, 2024 HiFiBiO Therapeutics, a leading clinical stage global biotechnology company committed to advancing patient outcomes through single-cell precision, reported two posters at the AACR (Free AACR Whitepaper) 2024 meeting held on April 5-10, 2024, in San Diego, CA (Press release, HiFiBiO Therapeutics, APR 7, 2024, View Source [SID1234641870]).

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"One of the major challenges cancer immunotherapies face is the difficulties in selecting patients with tumors that will respond. Single-cell technologies can provide valuable insights into disease biology and help discern tumors that are more likely to respond; however, the lack of integrated data across diverse single-cell platforms hinders the potential of these novel technologies to inform clinical decisions." Jack Russella-Pollard, Ph.D., Executive Director, Translational Data Science, commented, "HiFiBiO has built an AI/ML powered curation and data integration process within our Drug Intelligence Science (DIS) translational platform that integrates publicly available datasets with in-house generated datasets to predict tumor response and guide target as well as indication selection."

Jinping Gan, Ph.D., Vice President, Global Head of Research, remarked: "Currently, there is no suitable model to describe complex tumor-immune interactions that can effectively guide clinical decisions. HiFiBiO has successfully constructed semi-mechanistic PKPD models for an anti-TNFR2 agonist and an anti-OX40 agonist that advocate for pulsatile agonism to achieve optimal anti-tumor efficacy. This innovative scientific work serves as a valuable tool for guiding dose and dose regimen optimization for the humanized versions of these T cell co-stimulatory agonists in clinical development."

By harnessing these cutting-edge technologies and tools within its DIS platform, HiFiBiO Therapeutics is steering the development of its drug candidates, including three antibodies currently undergoing Phase 1 evaluation: a first-in-class TNFR2 agonist (HFB200301, NCT05238883), a next-generation OX40 agonist (HFB301001, NCT05229601), and a best-in-class BTLA antagonist (HFB200603, NCT05789069).

These presentations underscore HiFiBiO Therapeutics’ unwavering commitment to innovation and its relentless pursuit of novel therapeutic solutions to address unmet medical needs.

Details on the poster presentations are as follows. E-Posters will be posted on HiFiBiO’s website following the live presentations.

Abstract Number: 6202

Title: Integrating public single-cell transcriptomics and patient profiles to guide clinical development

Presenter: Jack Russella-Pollard, Ph.D., Executive Director, Translational Data Science
Session Category: Bioinformatics / Computational Biology / Systems Biology / Convergent Science

Session Title: Integrative Cancer Science

Session Date and Time: Tuesday Apr 9, 2024, 1:30 PM – 5:00 PM

Location: Poster Section 36

Poster Board Number: 5

View full abstract here.

Abstract Number: 7176

Title: Optimization of T cell co-stimulatory agonists: A semi-mechanistic PKPD model integrating drug properties and tumor-immune interactions

Presenter: Jinping Gan, Ph.D., Vice President, Global Head of Research

Session Category: Experimental and Molecular Therapeutics

Session Title: Pharmacology and Pharmacogenetics

Session Date and Time: Wednesday Apr 10, 2024, 9:00 AM – 12:30 PM

Location: Poster Section 24

Poster Board Number: 17

View full abstract here.

On April 7, 2024 Edgewood Oncology, a clinical-stage biotechnology company focused on delivering BTX-A51 to patients with hematologic malignancies and genetically-defined solid tumors, reported the publication of new preclinical data from a study of BTX-A51 in human liposarcoma (LPS) conducted by Dana-Farber Cancer Institute and Hebrew University-Hadassah Medical School to be presented at the AACR (Free AACR Whitepaper) Annual Meeting 2024 in San Diego (Press release, Edgewood Oncology, APR 7, 2024, View Source [SID1234641851]). BTX-A51 is a first-in-class, small molecule, multi-selective kinase inhibitor of casein kinase 1 alpha (CK1α) as well as the transcriptional regulators cyclin-dependent kinases 7 and 9 (CDK7 and CDK9) that synergistically co-targets master regulators of cancer to promote programmed cell death, or apoptosis.

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The presentation (Abstract 604), "Targeting casein kinase 1 alpha (CK1alpha) and transcriptional CDKs (CDK7/9) in human liposarcomas," highlighted findings for BTX-A51 in preclinical human models of LPS. The data demonstrate that BTX-A51 has preclinical efficacy in treating patient-derived LPS in cell lines and human xenograft models and provides insight into the synergy gained by inhibiting both CK1α and CDK9.

"Dedifferentiated liposarcomas (DDLPS) are rare tumors derived from precursors of fat cells which can occur anywhere in the body. Patients with metastatic DDLPS face a life-threatening disease in need of more effective therapeutic options, which we hope to develop by taking advantage of vulnerabilities in LPS that have been uncovered by recent research on the abnormal DNA and other molecular characteristics of LPS," said George Demetri, M.D., Professor of Medicine and director of the Sarcoma Center at Dana-Farber. "Based on these data, we believe that it is justified to move BTX-A51 into a clinical trial for patients with LPS, which we will plan to open soon for enrollment."

Liposarcomas are universally characterized by amplification of the mouse double minute 2 homolog (MDM2) gene, which leads to destruction of the normal (non-mutated, also known as "wild type") p53. The data demonstrate that BTX-A51 significantly reduces the abnormal overexpression of MDM2 in multiple patient-derived LPS cell lines, leading to upregulation of p53 expression and ultimately apoptosis. Finally, BTX-A51 was demonstrated to be well-tolerated and effective in an LPS patient-derived xenograft model.

"We’re pleased that investigators at Dana-Farber have taken an interest in BTX-A51, which is currently being evaluated in a Phase 2 combination study with azacitidine in patients with relapsed or refractory (R/R) AML," said David N. Cook, Ph.D., chief executive officer of Edgewood Oncology. "These data also suggest the potential for BTX-A51 in cancers with MDM2 amplifications, a group of genetically defined tumors that span multiple tissue types suggesting broader potential."

Additional Details about the Study

Using three different CDK9-selective inhibitors in human LPS cell lines, the authors showed that CDK9 inhibition suppressed cell growth and induced apoptosis by decreasing MDM2 levels while inducing expression of p53. It was also demonstrated that the potency of CDK9 inhibitors is significantly enhanced upon CK1α depletion. These data led to the investigation of BTX-A51, which targets CK1α and CDK9 as well as CDK7, in LPS cells and has previously been shown to inhibit these kinases with nanomolar efficacy in AML models. BTX-A51 potently reduced expression of MDM2 with marked induction of p53, resulting in apoptosis of LPS cells. BTX-A51 also reduces expression of MCL1 and primes LPS cell lines and primary LPS cells for BIM-induced apoptosis, as demonstrated by BH3 profiling. Importantly, preliminary in vivo data in an LPS patient-derived xenograft model reveal that BTX-A51 is well-tolerated under conditions that inhibit tumor growth.