On May 27, 2022 Enterome, a clinical stage biopharmaceutical company developing first-in-class immunomodulatory drugs based on its bacterial Mimicry drug discovery platform, reported the publication of three abstracts related to its OncoMimcs pipeline, including EO2401, its first-in-class off-the-shelf OncoMimics cancer immunotherapy, ahead of poster presentations at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, taking place June 3-7, 2022 in Chicago and virtually (Press release, Enterome, MAY 27, 2022, View Source [SID1234615168]).

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Enterome will present clinical proof-of-concept data from its most advanced OncoMimics drug candidate, EO2401, a therapeutic cancer vaccine candidate currently in clinical development for the treatment of patients with first progression/recurrence of glioblastoma (ROSALIE trial, EOGBM1-18) and for the treatment of patients with locally advanced or metastatic adrenocortical carcinoma, or malignant pheochromocytoma/paraganglioma (SPENCER trial, EOADR1-19).

A third poster describing the Phase 1/2 trial (SIDNEY, EONHL1-20) with Enterome’s second OncoMimics vaccine, EO2463, in non-Hodgkin lymphoma will also be presented at ASCO (Free ASCO Whitepaper).

Details of the poster presentations and session are as follows:

ROSALIE Trial (EOGBM1-18)

Title: EO2401, a novel microbiome-derived therapeutic vaccine for patients with recurrent glioblastoma
Track: Central Nervous System Tumors
Abstract number: #2034
Date and Time: Sunday, June 5, 8:00 AM-11:00 AM CDT
Presenter: Professor Wolfgang Wick, Universitätsklinikum Heidelberg and German Cancer Research Center, Heidelberg, Germany
Authors: Wick, W. et al
SPENCER Trial (EOADR1-19)

Title: EO2401, a novel microbiome-derived therapeutic vaccine for patients with adrenocortical carcinoma (ACC)
Track: Genitourinary Cancer—Kidney and Bladder
Abstract number: #4596
Date and Time: Saturday, June 4, 1:15 PM-4:15 PM CDT
Presenter: Professor Vivek Subbiah, The University of Texas MD Anderson Cancer Center (MDACC), Houston, TX
Authors: Baudin, E. et al
SIDNEY Trial (EONHL1-20)

Title: A novel microbial-derived peptide therapeutic vaccine (EO2463) as monotherapy and in combination with lenalidomide and rituximab, for treatment of patients with indolent non-Hodgkin lymphoma
Poster session: Hematologic Malignancies/Lymphoma and Chronic Lymphocytic Leukemia
Poster number: #TPS7586
Date and Time: Saturday, June 4, 8:00 -11:00 AM CDT
Authors: Zinzani, P.L et al

About OncoMimics Peptides

OncoMimics peptides are gut microbiome-derived peptides that closely mimic antigens expressed by tumor cells. In contrast to tumor antigens, however, OncoMimics peptides are recognized by the immune system as "non-self" and can generate a strong human cytotoxic CD8+ response steming from memory T cells, offering enormous potential to create a new class of cancer vaccines targeting solid and liquid tumors.

Enterome’s pioneering work on its OncoMimics pipeline leverages the fundamental understanding that the gut is the largest lymphoid organ in the body and is home to most of its memory T-cells. As a result, there is constant interaction and presentation of peptides and proteins secreted by gut bacteria to the body’s immune system, resulting in the formation of a pool of effector memory T cells protecting the human body against bacterial invasion. In the event that the bacterial antigens are mimics of tumor antigens, this process leads to the generation of circulating effector memory T cells with a preserved ability to recognize tumor antigens.

On May 27, 2022 Targovax ASA (OSE: TRVX), reported that publication of the two ONCOS-102 abstracts accepted for presentation at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting 3-7 June 2022 (Press release, Targovax, MAY 27, 2022, View Source [SID1234615167]). The posters will present clinical results from the completed phase 1/2 trials in malignant pleural mesothelioma and in heavily pre-treated, MS-stable colorectal or ovarian cancer with peritoneal metastasis.

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First poster title: Final survival outcomes and immune biomarker analysis of a randomized, open-label, phase I/II study combining oncolytic adenovirus ONCOS-102 with pemetrexed/cisplatin (P/C) in patients with unresectable malignant pleural mesothelioma (MPM)
Session Title: Lung Cancer – Non-Small Cell Local-Regional/Small Cell/Other Thoracic Cancers
Time: Monday 6 June 2022, 8:00-11:00 AM CDT, Abstract 8561
Presenter: Dr Santiago Ponce, Medical Oncology, Hospital 12 Octubre, Madrid, Spain

The poster summarizes the overall findings from the completed, randomized phase 1/2 trial in 31 patients with MPM; 20 patients received intra-tumoral (IT) ONCOS-102 in combination with standard of care (SoC) chemotherapy and 11 patients in a control group received SoC chemotherapy only.

In the randomized part of the trial, the 30-month overall survival (OS) rate was 34.3% in the ONCOS-102 treated group (n=14) vs. 18.2% in the SoC-only control group (n=11). In first-line patients, the ONCOS-102 group achieved a median overall survival (mOS) of 25.0 months (n=8) vs. 13.5 months mOS in the SoC-only control group (n=6). The ONCOS-102 first-line mOS compares favorably to SoC historical control studies reporting mOS of 12-16 months1, as well as the combination of nivolumab and ipilimumab which demonstrated mOS of 18.1 months in a phase 3 trial that led to FDA approval2. Tumor biopsy immune cell analyses revealed strong T-cell infiltration induced by ONCOS-102 in patients with partial response (PR) or stable disease (SD), but not in progressors. These observations were confirmed by RNAseq gene expression analysis. The breadth and strength of immune response induced by ONCOS-102 correlated with both tumor response and survival. Further clinical trials in MPM are clearly warranted to validate these positive findings in a larger patient cohort.

Second poster title: Study to evaluate intraperitoneal (IP) ONCOS-102 with systemic durvalumab in patients with peritoneal disease who have epithelial ovarian (OC) or metastatic colorectal cancer (CRC): Phase 2 results
Session Title: Development Therapeutics, Immunotherapy
Time: Sunday 5 June 2022, 8:00-11:00 AM CDT, Abstract 2600
Presenter: Dr Dmitriy Zamarin, Memorial Sloan Kettering Cancer Center, New York, USA

The poster reports clinical data from the ONCOS-102 phase 1/2 combination trial with anti-PD-L1 checkpoint inhibitor durvalumab in heavily pre-treated, MS-stable CRC (n=36) or OC (n=19) with peritoneal metastases. This is a patient population with few treatment alternatives that only offer marginal efficacy and where checkpoint inhibitor monotherapy does not have any meaningful activity. The trial was managed by an external consortium with Ludwig Cancer Research as sponsor, where Targovax was a collaboration partner.

This is the first time ONCOS-102 has been administered IP and in combination with an anti-PD-L1 checkpoint inhibitor. IP delivery of ONCOS-102 was demonstrated to be feasible and well-tolerated, both as monotherapy and in combination with systemic durvalumab. Whereas the initial OC cohort did not meet the efficacy criteria and was closed, the initial CRC cohort met the efficacy criteria and was expanded. In the full CRC cohort (n=36) two patients remained progression free at the end of the study (week 24), but the primary efficacy endpoint of 4 patients remaining progression free at week 24 was not met.

Tumor biopsy immune cell analysis showed increased T-cell infiltration in several patients, confirming that IP administered ONCOS-102 can induce immune activation in heavily pre-treated, immunologically silent solid tumors. Of note, the selected IP dose was the same as used for IT delivery of ONCOS-102 (3×1011 V.P.), although IP delivery is expected to result in lower tumor exposure to the virus relative to IT. Hence, higher doses of IP delivered ONCOS-102 could potentially enhance both the immunological response and clinical activity.

Dr. Lone Ottesen, Chief Medical Officer of Targovax, said: "We are very pleased to have two ONCOS-102 studies accepted for presentation at ASCO (Free ASCO Whitepaper) this year, which is a very important forum to showcase and discuss our clinical data with international experts in the field. In our exploratory clinical program we have now demonstrated that ONCOS-102 can be delivered safely intra-tumorally and intra-peritoneally in combination with PD-1 and PD-L1 checkpoint inhibitors, as well as chemotherapy. Importantly, we have also seen robust immunological and clinical activity in solid tumors of different origins. This gives us confidence to bring ONCOS-102 forward into later stage development, with the first step being a multi-cohort phase 2 trial in PD1-refractory melanoma where we will test several I-O combinations, including the second-generation anti-CTLA4 checkpoint inhibitor botensilimab."

About ASCO (Free ASCO Whitepaper)
American Society of Clinical Oncology Annual Meeting, ASCO (Free ASCO Whitepaper) 2022 will be held in McCormick Place, Chicago, Illinois, United States between 3-7 June 2022.

The 2022 ASCO (Free ASCO Whitepaper) Annual Meeting Program will offer presentations on the latest research in cancer care. This year’s program will feature sessions complementing the meeting’s theme: Advancing Equitable Cancer Care Through Innovation.

On May 26, 2022 SOTIO Biotech, a clinical stage immuno-oncology company owned by PPF Group, reported updated interim safety and efficacy data from its Phase 1/1b AURELIO-03 dose escalation study of the IL-2/IL-15 receptor βγ superagonist, SOT101, as monotherapy and in combination with pembrolizumab in patients with advanced solid tumors (Press release, SOTIO, MAY 26, 2022, View Source [SID1234626226]). Data from the study show that SOT101 has a favorable safety profile. The recommended Phase 2 dose was defined at 12 µg/kg SOT101.

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The AURELIO-03 study is an open label, single arm Phase 1/1b dose escalation study to determine the recommended Phase 2 dose and to evaluate the preliminary efficacy of SOT101 in patients with advanced solid tumors either as a monotherapy or in combination with pembrolizumab. SOT101 is administered subcutaneously on days 1, 2, 8, and 9 of every three-week cycle. 30 patients were treated on monotherapy dose levels 0.25 to 15 μg/kg and twenty-one patients on combination therapy dose levels 1.5 to 12 μg/kg.

Interim results of SOT101 as a monotherapy demonstrated four patients pretreated with checkpoint inhibitor (CPI) with confirmed stable disease. A partial response was confirmed in one patient with skin squamous cell carcinoma whose tumor was CPI-refractory. The preliminary efficacy is currently being further evaluated in an ongoing monotherapy extension in skin squamous cell carcinoma, melanoma, and renal cell cancer.

In 19 patients with at least one post-baseline tumor assessment across all dose levels who were treated with SOT101 in combination with pembrolizumab, one complete response in a patient with mesothelioma, four partial responses and 10 confirmed stable diseases have been reported.

The adverse event profile of SOT101 in combination with pembrolizumab was in line with the adverse event profile of either compound as monotherapy. No additive toxicity was seen when combining SOT101 with pembrolizumab. For both monotherapy and combination treatment, the recommended Phase 2 dose of SOT101 was established at 12 μg/kg.

This data will be presented by principal investigator Dr. Elena Garralda from the Vall D’Hebron Institute of Oncology, Barcelona, Spain at the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in Chicago, Illinois on Saturday, June 4, 2022.

"Despite decades of progress in clinical oncology, the difficulty of treating solid tumors has remained a significant challenge for physicians," said Radek Spisek, M.D., Ph.D., chief executive officer of SOTIO. "Given the promising results from our first-in-human study of SOT101, we are greatly encouraged to have observed excellent preliminary safety and efficacy data both as a monotherapy and in combination with pembrolizumab. We look forward to initiating a basket study of SOT101 in combination with KEYTRUDA to evaluate efficacy and safety in patients with selected advanced or refractory solid tumors. This large Phase 2 AURELIO-04 trial in collaboration with MSD will be initiated in the coming weeks."

Dr. Garralda added: "The patients in this study are some of the hardest to treat, some with up to nine prior lines of therapy, so the clinical benefit observed in the AURELIO-03 study is especially encouraging. These data highlight the potential impact of SOT101 on the treatment landscape for solid tumors."

The presentation from ASCO (Free ASCO Whitepaper) is available below:

ASCO 2022 – AURELIO-03 results.pdf

About SOT101:
SOT101 (SO-C101) is a subcutaneously administered IL-15Rβγ superagonist that is fused to the sushi+ domain of the IL-15 receptor α chain. SOT101 has demonstrated strong preclinical in vivo efficacy in various tumor models showing increased long-term survival and tumor regression, as well as a favorable toxicology profile. SOT101 has been shown in pre-clinical models to synergize with checkpoint inhibitors and antibody therapies exerting ADCC.

On May 26, 2022 Chiome Bioscience Inc. reported joint research agreement with Kidswell Bio Corporation (Press release, Chiome Bioscience, MAY 26, 2022, View Source [SID1234625711]). The collaborative research makes us join their ongoing research project to develop therapeutic antibody for cancer.

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Our mission is to shine the light on unmet medical needs through our research project of drug discovery and development. This collaborative research will expect to merge our research functions and experiences with novel antibody drug discovery project. We will continue to discuss the extended collaboration scheme with Kidswell Bio in case our joint research make the progress pushing the project up to the therapeutic drug development stage.

On May 26, 2022 Onconova Therapeutics, Inc. (NASDAQ: ONTX), a clinical-stage biopharmaceutical company focused on discovering and developing novel products for patients with cancer, reported the publication of an abstract at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (Press release, Onconova, MAY 26, 2022, View Source [SID1234615195]). Featured in the abstract are preclinical data from in vitro and cell-based assays that demonstrate how narazaciclib’s inhibitory profile differentiates it from the FDA-approved CDK4/6 inhibitors palbociclib, ribociclib, and abemaciclib.

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Key data and conclusions from the abstract include:

Narazaciclib, abemaciclib, palbociclib, and ribociclib each have strong affinity for CDK4/cyclin D1, with Kd values of 0.18 nM, 0.08 nM, 0.75 nM, and 1.3 nM, respectively.

Narazaciclib and abemaciclib have similar affinities against CDK family members, including nM activity against CDK2/cyclin A, which may play a role in resistance to palbociclib and ribociclib.

Narazaciclib’s inhibitory activity against GSK3β, a kinase whose inhibition putatively causes tolerability issues related to diarrhea, is ~29 times less than that of abemaciclib.

Cellular kinase assays showed narazaciclib’s highest inhibitory activity to be against CDK4/6, CSF1R, (supports pro-tumor immune suppression), and NUAK1/ARK 5 (associated with poor prognosis in multiple cancers and implicated in cancer cell migration, invasion, and metastasis).

Cellular Thermal Shift Assay (CETSA) and integrative Inferred Kinase Activity (INKA) analysis showed that narazaciclib is associated with and modulated unique signaling pathways resulting in specific deregulated phosphorylation patterns when compared to palbociclib treated cells.
Steven M. Fruchtman, M.D., President and Chief Executive Officer of Onconova and co-author of the abstract, commented, "Though revolutionary and commercially successful, currently available CDK4/6 inhibitors are limited by tolerability and safety issues as well as the unfortunate reality of primary and acquired drug resistance. This creates a pressing unmet need for novel agents that may overcome these shortcomings and provide patients with durable clinical benefit. Narazaciclib’s decreased affinity for targets associated with poor tolerability, together with its increased inhibitory activity against kinases implicated in metastasis, cancer cell survival, immune suppression, and drug resistance, suggests it may address this need. We continue to explore this hypothesis in narazaciclib’s clinical program and remain on track to establish a recommended Phase 2 dose by the end of the year."

A copy of the abstract, titled, "Narazaciclib’s kinase inhibitory activity is differentiated from approved CDK4/6 inhibitors in preclinical models," is available on the ASCO (Free ASCO Whitepaper) Annual Meeting website.