On November 4, 2023 sairopa.com – a clinical-stage company that develops novel treatments for cancer by modulating the patient’s immune system, reported early clinical data on ADU-1604, its proprietary anti-CTLA4 antibody at the SITC (Free SITC Whitepaper) 38th Annual Meeting (Press release, Sairopa, NOV 4, 2023, View Source [SID1234636973]). Data obtained from the ongoing Phase 1 dose-escalation stage in PD1 relapse/refractory melanoma patients (N=17) were presented. ADU-1604 is well tolerated at the dosages tested (25, 75, 225 and 450 mg Q3W). No dose-limiting toxicities or treatment-related severe adverse events have been reported up to now. Pre-clinical data was presented that potentially explains the suggested improved safety profile of ADU-1604 vs. other anti-CTLA4 antibodies. ADU-1604 was shown to dose-dependently increase pharmacodynamic biomarkers, which correlates with early signs of clinical activity. Finally, early clinical efficacy data was reported showing one unusually long stable disease and two ongoing tumor regressions.

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On November 4, 2023 Promontory Therapeutics Inc., a Phase 2 stage biotech company advancing immunogenic small molecule approaches in oncology, reported data demonstrating the molecular mechanism of its lead therapeutic candidate, PT-112, and its ability to induce immunogenic cell death (ICD) in cancer cells (Press release, Promontory Therapeutics, NOV 4, 2023, View Source [SID1234636971]). Data suggest that PT-112-induced ICD is mediated by endoplasmic reticulum (ER) and mitochondrial stresses, which are specific intra-cellular events that comprise part of the larger ICD mechanism. The presentation was made at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s (SITC) (Free SITC Whitepaper) 38th Annual Meeting, taking place November 1-5, 2023 in San Diego.

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The work was designed in collaboration with the Galluzzi Lab at Weill Cornell Medical College in New York, in order to elucidate the sequence of events – beginning with inhibition of ribosomal biogenesis and culminating in selective ICD – underlying PT-112’s immune effects. Analyzing a panel of mouse cell lines engineered to lack specific genes involved in mitochondrial apoptosis (Bcl2, Bax and Bak1), flow cytometry, immunoblotting, RT-PCR, and immunofluorescence microscopy were used to determine the impact of PT-112 on ER and mitochondrial stress, as well as immunogenic signaling.

"Our continued studies of PT-112 provide mechanistic insights for this promising immunogenic small molecule, which has shown clinical activity in patients with a variety of cancers," said Promontory Therapeutics Senior Vice President of Research and Development Tyler Ames, PhD. "This particular work sheds light on how PT-112 encourages the immunogenic cell death of cancerous cells through ER stress and mitochondrial dysfunction, both of which are known to contribute to immune signaling."

Study findings include:

PT-112 drives ER stress and mitochondrial dysfunction, which promote ICD.

PT-112 effects on mitochondria included increases in mitochondrial mass and reactive oxygen species, changes in membrane polarization, and the release of mitochondrial DNA into the cytosol, a potent immunogenic signal. Some of these effects were impacted by the absence of Bax and Bak1.

PT-112 elicits the phosphorylation of eukaryotic translation initiation factor 2 subunit alpha (EIF2S1, best known as eIF2α), indicating ER stress and the activation of the integrated stress response (ISR).

There is an increase in the levels of Ifnb1 mRNA after PT-112 exposure, indicating PT-112 induces type 1 interferon responses.

PT-112 is the subject of ongoing Phase 2 clinical trials for metastatic castrate-resistant prostate cancer and thymic epithelial tumors, and a completed Phase 2a trial in non-small cell lung cancer. In previous mechanism of action research, data showed that PT-112 causes ribosomal biogenesis inhibition and nucleolar stress, which is the likely driver of PT-112-induced cancer organelle stresses and ICD.

For more information about Promontory Therapeutics and PT-112, visit www.PromontoryTx.com.

About PT-112
PT-112 is a novel inhibitor of ribosomal biogenesis, which leads to selective immunogenic cancer cell death (ICD). PT-112’s mechanism of action governs intracellular events that cause the release of damage associated molecular patterns, known to bind to dendritic cell and natural killer cell receptors, prompting an anti-cancer immune response. PT-112’s potential best-in-class ICD effects may create the conditions for effective and durable responses to treatment. The first in-human study of PT-112 demonstrated an attractive safety profile and evidence of long-lasting responses among heavily pre-treated patients and data were published in eClinicalMedicine, part of The Lancet. The company’s Phase 2 study of PT-112 in late-stage metastatic castration-resistant prostate cancer patients is underway in the United States and France. An active Phase 2 trial is also on-going with the National Cancer Institute utilizing PT-112 in thymic epithelial tumors, a rare disease with no FDA approved drug, for which PT-112 has received FDA Orphan Drug designation. An additional Phase 2a study has been successfully completed for non-small cell lung cancer in combination with PD-L1 inhibition.

On November 3, 2023 Theralink Technologies, Inc. (OTC: THER) ("Theralink"), a precision oncology company with its exclusive commercial RPPA (reverse phase protein array) technology that can help predict which FDA-approved drug is effective in each cancer, reported that their long-standing, strategic partnership with the Inova Schar Cancer Institute (Inova) is beginning to deliver promising results by way of assessing the feasibility and impact of the actionable information provided by the Theralink assay into Inova’s Molecular Tumor Board (MTB)-based treatment decisioning making for cancer patients (Press release, Theralink Technologies, NOV 4, 2023, View Source [SID1234636909]).

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The partnership involves the integration of the Theralink assay, protected by ten patents, into Inova’s molecular tumor board’s operational workflow. Over the past year, Inova has undertaken a feasibility study to develop and implement the procedures and infrastructure necessary for proteomic analysis within the context of the Inova Schar Molecular Tumor Board. The Theralink assay provides a direct means of determining the actionability of genomic derangements identified, as well as directly measuring the activation/elevation of protein drug targets otherwise missed by genomic analysis alone. Thus, the incorporation of key phosphoprotein and protein data generated by Theralink’s RPPA technology into the Inova MTB could synergize with current genomics analysis to produce more accurate treatment selection and patient-tailored therapy regimes.

Interim results of this pan-tumor study were presented at the 2023 ASCO (Free ASCO Whitepaper) Conference in Chicago. Specifically, the analysis examined the feasibility of incorporating laser capture microdissection (LCM) enrichment of tumor specimens and reverse phase protein array (RPPA) analysis with next generation sequencing (NGS) into a molecular tumor board for improving selection of targeted cancer therapy. Integrated review of the RPPA and NGS data by the MTB supported a clinical recommendation change for over half of the patients overall. Further, the proteomics data from the Theralink assay provided additional treatment considerations for 59% of the patients, the outcomes for whom continue to be monitored. Moreover, the collaboration with Inova and their MTB resulted in a recent finding1 wherein the Theralink proteomics data revealed a specific mechanism of resistance and likely lack of benefit to a targeted therapy being considered by the MTB for a patient with a rare form of inflammatory myofibroblastic cancer.

Lastly, Inova and Theralink presented the results of another important study at ASCO (Free ASCO Whitepaper) 2023 that focused on Theralink’s unique ability to quantitatively measure HER2 abundance and activation and found that nearly 50% of pancreatic tumor actually express moderate amounts of HER2 protein, which could be missed by existing commercial HER2 assays. While HER2 expression is not routinely evaluated in clinical practice for pancreatic cancer these results may have clinical implications, especially as new classes of HER2 antibody drug conjugates are considered for patients with HER2 non amplified tumors across organ sites.

"Theralink is extremely encouraged by the work done to date at Inova Schar Cancer Institute- the interim results and clinical intelligence speak for themselves. We look forward to completing this study with Inova for our mutual goal of improving outcomes for all cancer patients", said Faith Zaslavsky, President and Chief Executive Officer of Theralink.

Dr. Timothy Cannon, who is the Sheridan Director of the Inova Molecular Tumor Board and Co-Director of the Gastrointestinal Cancer Program at Inova said, "We have tested over 100 patients with Theralink’s RPPA technology as part of this study. We are hopeful final study analysis and results will continue to underscore the importance of real-time clinical integration of functional protein drug target activation data provided by the Theralink assay with NGS in the Inova MTB for cancer patients."

Theralink and Inova will update findings and results post study completion. Published results are anticipated in early 2024.

On November 3, 2023 Acerand Therapeutics reported the approval of their next generation PARP1 selective inhibitor, ACE-86225106, for a first-in-human, open-label, multi-center Phase I/II study by the Center for Drug Evaluation of China National Medical Products Administration (Press release, Acerand Therapeutics, NOV 3, 2023, View Source [SID1234641763]).

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ACE-86225106 is a next generation PARP1 selective inhibitor with excellent in vitro and in vivo activity. Its markedly increased selectivity over other PARP isoforms, especially PARP2 and PARP3, has significantly improved its safety profile in in vitro and in vivo studies. Its differentiated pharmacokinetic property may result in better tolerability and more durable clinical activity. The low projected human dose in combination with high starting first in human dose could lead to rapid identification of recommended phase 2 dose. Due to its excellent potency, selectivity, and pharmacokinetic properties, ACE-86225106 can be used as a single agent and more importantly as a preferred combination partner with chemotherapies and targeted therapies in treating multiple solid tumors.

Given these promising data, Acerand Therapeutics will promptly initiate phase 1 dose escalation study in patients in China followed by the US to further assess the potential of ACE-86225106 as an effective mono- or combination therapy for treating different types of cancers, especially those with BRCA mutations or other homologous recombination deficiency.

Remarks by Dr. Genshi Zhao, Acerand Co-Founder, President and CSO:

We are very excited to begin clinical trials for our PARP1 inhibitor, ACE-86225106. The first-generation PARP inhibitors are known to have serious hematological and gastrointestinal toxicities due to the lack of selectivity over PARP2 and other isoforms. These serious toxicities have limited their clinical utility, especially in combination therapies. With its markedly increased selectivity over PARP2, significantly improved safety profile, excellent in vitro and in vivo potency, and PK profile, ACE-86225106 is expected to have great potential as a safer and more effective treatment option for cancer patients. We are confident that ACE-86225106’s clinical performance will greatly benefit cancer patients in China and elsewhere.

On November 3, 2023 Oncolytics Biotech, a clinical-stage immunotherapeutics company focused on oncology, reported recent operational highlights and financial results for the third quarter ended September 30, 2023 (Press release, Oncolytics Biotech, NOV 3, 2023, View Source [SID1234639000]). All dollar amounts are expressed in Canadian currency unless otherwise noted.

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"We continue to build our case for pelareorep to be an important immunotherapy in multiple large and in-need cancer indications," said Dr. Matt Coffey, President and Chief Executive Officer. "The ESMO (Free ESMO Whitepaper) presentations show the first batch of survival data from first-line metastatic pancreatic cancer patients exceeds the historical averages recorded in control trials, aligning with the positive response data we first reported at SITC (Free SITC Whitepaper) last year. They also reveal that pelareorep can generate an immune response in heavily pre-treated metastatic colorectal cancer patients. I’m pleased to note that GOBLET has now reported consecutive indications where pelareorep-based therapy has met the success criteria for efficacy, validating our decision to explore pelareorep in gastrointestinal indications in combination with the checkpoint inhibitor atezolizumab. The compelling GOBLET results were instrumental in obtaining a US$5 million grant from PanCAN to explore pelareorep in combination with modified FOLFIRINOX (mFOLFIRINOX) with and without atezolizumab in pancreatic cancer patients."

Dr. Coffey continued, "Having already observed efficacy signals in pancreatic cancer from the combination of pelareorep and atezolizumab plus the standard of care regimen gemcitabine and nab-paclitaxel, we believe that with encouraging efficacy signals from a pelareorep and mFOLFIRINOX combination, we have the potential to become the go-to treatment option for a substantial number of pancreatic cancer patients."

Third Quarter and Subsequent Highlights

Pancreatic Cancer Program

Updated data reported at ESMO (Free ESMO Whitepaper) shows robust survival and translational data

A poster with data from the pancreatic cancer cohort of the Phase 1/2 GOBLET study was presented at the European Society for Medical Oncology (EMSO) Congress 2023 (link to the PR, link to the poster). This study cohort was designed to evaluate pelareorep in combination with atezolizumab and the chemotherapeutic agents gemcitabine and nab-paclitaxel in patients with advanced or metastatic pancreatic cancer. The efficacy results presented exceeded those from earlier studies, including a 62% objective response rate, a median progression-free survival of 7.2 months, an interim median overall survival of 10.6 months, and a 46% interim 12-month survival rate. These data also demonstrated the ability of pelareorep-based combination therapy to induce the expansion of both pre-existing and new T-cell clones from the tumor. This combination therapy has already been selected for inclusion in the Precision PromiseSM Pivotal Phase 3 Platform Trial (link to the PR).

Pancreatic Cancer Action Network (PanCAN) award and grant

Oncolytics was awarded the Therapeutic Accelerator Award, which includes a US$5 million grant from PanCAN, to initiate a Phase 1/2 randomized clinical trial of pelareorep combined with modified FOLFIRINOX, with or without the checkpoint inhibitor atezolizumab (link to the PR). We anticipate that the combination therapy that performs best will be further evaluated in a licensure-enabling study, such as the Precision PromiseSM Pivotal Phase 3 Platform Trial. The combination of pelareorep, gemcitabine, nab-paclitaxel, and atezolizumab has already been selected for inclusion in Precision Promise, with the trial expected to open in the first half of 2024.

Colorectal Cancer Data

ESMO presentation shows the third-line colorectal cancer cohort met its success criteria for efficacy

A poster presentation at ESMO (Free ESMO Whitepaper) announced interim results from the third-line metastatic colorectal cancer cohort of the Phase 1/2 GOBLET study (link to the PR, link to the poster). In a patient population that failed two prior lines of treatment, six of 15 patients recorded stable disease as their best response, and four had stable disease at week 16 or later, thereby meeting the prespecified success criteria for stage 1 of the study. The disease control rate was 40%, the median progression-free survival was 2.8 months, the median overall survival was 8.0 months, and the 12-month survival rate was 33%.

Breast Cancer Program

AWARE-1 abstract data reported at SITC (Free SITC Whitepaper) reinforces pelareorep’s ability to remodel the tumor microenvironment, poster to be available later today

Additional data from the AWARE-1 breast cancer study was reported in an abstract at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 38th Annual Meeting. AWARE-1 evaluated early-stage breast cancer patients in two cohorts who received pelareorep and letrozole with and without atezolizumab. The study met its primary endpoint of CelTIL score (a measurement of cellularity and tumor-infiltrating lymphocytes), with the arm that included atezolizumab showing enhanced outcomes. Further analysis of the tumor microenvironment of patient tissue samples was performed using imaging mass cytometry (IMC). The data show increased PD-L1 positive cells and an increase in cytotoxic T cells, amongst other benefits, which make the tumor microenvironment more amenable to treatment. The SITC (Free SITC Whitepaper) poster embargo lifts at 9 a.m. Pacific Time today, November 3, 2023, and the poster will be available on the Oncolytics website shortly after that.

Financial Highlights

As of September 30, 2023, the Company reported $40.0 million in cash and cash equivalents, with a projected cash runway for at least 12 months.
Net cash used in operating activities for the nine months ended September 30, 2023 was $22.3 million, compared to $17.4 million for the nine months ended September 30, 2022. The change reflected higher net operating activities.
General and administrative expenses for the third quarter of 2023 were $5.2 million, compared to $2.4 million for the third quarter of 2022. The increase was primarily due to higher investor relations activities and the portion of the public offering transaction costs allocated to general and administrative expenses.
Research and development expenses for the third quarter of 2023 were $5.8 million, compared to $3.7 million for the third quarter of 2022. The increase was primarily due to higher manufacturing expenses as we completed a scaled-up engineering production run and the associated batch testing. The increase was partly offset by lower clinical trial expenses related to clinical and safety data management.
The net loss for the third quarter of 2023 was $9.9 million, compared to a net loss of $4.4 million for the third quarter of 2022. The basic and diluted loss per share was $0.14 in the third quarter of 2023, compared to a basic and diluted loss per share of $0.08 in the third quarter of 2022.
Anticipated Milestones and Catalysts

Interim data from the GOBLET study’s anal cancer cohort: Q4 2023
Initiation of the Precision PromiseSM Pivotal Phase 3 Platform Trial in first-line metastatic pancreatic ductal adenocarcinoma (PDAC) patients: H1 2024
Initiation of the PanCAN supported Phase 1/2 combination study of pelareorep and modified FOLFIRINOX in newly diagnosed metastatic PDAC patients: H1 2024
BRACELET-1 Phase 2 metastatic breast cancer study overall survival data
Webcast and Conference Call

Management will host a conference call for analysts and investors at 8:30 a.m. ET today, November 3, 2023. To access the call, please dial (888) 664-6383 (North America) or (416) 764-8650 (International) and, if needed, provide Conference ID: 6026-0546. To join the conference call without operator assistance, please click here. A live webcast of the call will also be available by clicking here or on the Investor Relations page of Oncolytics’ website (LINK) and will be archived for three months. A dial-in replay will be available for one week and can be accessed by dialing (888) 390-0541 (North America) or (416) 764-8677 (International) and using replay code: 260-546#.