On April 10, 2021 OncoMyx Therapeutics, a privately-held oncolytic immunotherapy company, reported the presentation of three posters at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Virtual Annual Meeting I, taking place April 10-15, 2021 (Press release, OncoMyx Therapeutics, APR 10, 2021, View Source [SID1234577861]). The data are the first to demonstrate that OncoMyx’s multi-armed myxoma virotherapy upregulates anti-tumor immune response pathways, expresses transgenes in a dose and time-dependent manner, and produces anti-tumor efficacy in a preclinical model of cancer following intravenous (IV) or intratumoral (IT) dosing. In addition, new data show that IV administration of myxoma virus produces minimal anti-myxoma antibodies in vivo in a preclinical model and falls within known safety margins of predicted cytokine exposure using quantitative in silico modeling.

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Further data were also presented building upon data presented at SITC (Free SITC Whitepaper) 2019 confirming that myxoma virus is oncolytic across a board range of human cancer cell lines in vitro, is efficacious in syngeneic models following IV or IT delivery, and carries and functionally produces multiple transgenes in vivo. One of OncoMyx’s myxoma virotherapies (vMYX-hIL-12/Dec), which is multi-armed with interleukin-12 (IL-12) and decorin (Dec), upregulates interferon-α (IFN-α), and IFN-γ, and IL-12 response pathways, which are associated with anti-tumor immune response. Previous data presented at SITC (Free SITC Whitepaper) 2019 showed evidence that OncoMyx’s multi-armed myxoma virotherapy modulates tumor infiltrating lymphocytes populations, including increased CD8/Treg and M1/M2 macrophage ratios, to favor anti-tumor immunity and provides combinatorial efficacy with immune checkpoint inhibitors.

"We are steadfastly building a substantial amount of data supporting the safety and efficacy of our multi-armed myxoma virotherapy as an important oncolytic immunotherapy for the treatment of cancer," said Leslie L. Sharp, Ph.D., chief scientific officer of OncoMyx. "These data presented over the last five months show myxoma virus can be constructed to stimulate anti-tumor immunity and produce anti-tumor efficacy in a wide range of models following IV or IT administration."

"We believe that multi-armed viruses that are capable of IV delivery are what’s necessary to unlock the power of oncolytic immunotherapy, and it’s clear that not all viruses can balance this," said Steve Potts, Ph.D., MBA, cofounder and chief executive officer of OncoMyx. "That’s why we’ve focused on the myxoma virus. It’s truly a unique virus that inherently has all the qualities that we can leverage to create a best-in-class, systemic, targeted oncolytic immunotherapy."

The posters will be available for viewing in the virtual poster hall on Saturday, April 10, starting at 8:30 am ET and available for download on OncoMyx’s website. Details of the presentations are as follows:

1919: Prediction of systemic cytokine exposure in human after IV administration of oncolytic myxoma virus, using quantitative systems pharmacology modeling
1920: Armed oncolytic myxoma virus demonstrates transgene production, function, and therapeutic activity xenograft models
1921: Armed myxoma virus demonstrates transgene expression, efficacy, and immune system modulation in syngeneic tumor models
About Myxoma Virus and Oncolytic Immunotherapy

Oncolytic viruses selectively replicate in and lyse tumor cells and provide stimulation to the immune system, representing a promising therapeutic option in development to treat cancers that do not respond well to immune checkpoint inhibitors. As a large double-stranded DNA pox virus, myxoma is ideal for multi-armed, targeted, systemic oncolytic immunotherapy. Because the natural host of myxoma is a subset of rabbits and hares, it doesn’t have to overcome preexisting human immunity. While it is not pathogenic to humans, extensive research shows myxoma can selectively infect and kill a wide variety of human cancer types in vitro and in preclinical in vivo models. OncoMyx has specifically built multi-armed myxoma viruses with immunomodulatory proteins and payloads designed to stimulate anti-tumor immunity and deliver targeted cancer therapies. For more information, visit www.oncomyx.com/platform.

On April 10, 2021 Sysmex Inostics, Inc., a global leader of the liquid biopsy revolution for oncology,reported the poster "Clinical evaluation of NGS-based liquid biopsy testing in non-small cell lung cancer (NSCLC) patients" at the 112th Annual Meeting of the American Association for Cancer Research (AACR) (Free AACR Whitepaper) on April 10, 2021, from 8:30 AM – 11:59 PM Eastern Daylight Time (EDT) (Press release, Sysmex, APR 10, 2021, View Source [SID1234577877]).

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In a recent collaborative study, Johns Hopkins University School of Medicine and Sysmex Inostics’ researchers showed that the next-generation sequencing (NGS)-based liquid biopsy SafeSEQ NSCLC panel delivers equivalent performance with broader genomic coverage than testing with OncoBEAM digital PCR (dPCR). OncoBEAM technology is widely considered a gold standard for high sensitivity molecular testing and continues to be one of the most sensitive dPCR approaches.

SafeSEQ technology demonstrates ultra-sensitive detection of low-frequency mutations, with a calling threshold of 5 mutant molecules (0.025% mutant allele frequency [MAF]) from whole blood. Concordance analysis of SafeSEQ and OncoBEAM results demonstrated an overall percent agreement of 99.6% for detection of mutations in EGFR, KRAS, and BRAF (>0.1% MAF).

The 5-year survival rate for metastatic NSCLC (mNSCLC) patients is relatively low; however, it has improved with the advent of targeted therapies and uptake of circulating tumor DNA (ctDNA) based technologies in recent years. In groundbreaking NSCLC clinical trials AURA and TIGER-X, patients positive for EGFR T790M detected in plasma by OncoBEAM had equivalent outcomes to patients positive by a tissue-based assay when treated with third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), which have demonstrated potent activity against first-line EGFR TKI resistance mediated by EGFR T790M.

SafeSEQ NSCLC testing delivers broader genomic coverage than OncoBEAM, with the same ultra-sensitive detection for rare mutant molecules. Therefore, SafeSEQ is better suited to identify molecular mediators of treatment resistance to improve therapeutic strategies, delivering high-resolution monitoring of therapeutic efficacy, and enabling minimum residual disease (MRD) detection and recurrence surveillance for NSCLC patients.

Poster number LB053, "Clinical evaluation of NGS-based liquid biopsy genotyping in non-small cell lung cancer (NSCLC) patients," presented by Hillary Sloane, Associate Director of Medical & Scientific Affairs at Sysmex Inostics, will be available Saturday, April 10, 2021, from 8:30 AM – 11:59 PM EDT during the 112th Annual Meeting of the American Association for Cancer Research (AACR) (Free AACR Whitepaper) during Session PO.CL11.04 – Liquid Biopsies: Circulating DNA.

On April 10, 2021 Sysmex Inostics, Inc., a global leader of the liquid biopsy revolution for oncology, reported the poster "Clinical evaluation of NGS-based liquid biopsy testing in non-small cell lung cancer (NSCLC) patients" at the 112th Annual Meeting of the American Association for Cancer Research (AACR) (Free AACR Whitepaper) on April 10, 2021, from 8:30 AM – 11:59 PM Eastern Daylight Time (EDT) (Press release, Sysmex Inostics, APR 10, 2021, View Source [SID1234577829]).

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Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

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In a recent collaborative study, Johns Hopkins University School of Medicine and Sysmex Inostics’ researchers showed that the next-generation sequencing (NGS)-based liquid biopsy SafeSEQ NSCLC panel delivers equivalent performance with broader genomic coverage than testing with OncoBEAM digital PCR (dPCR). OncoBEAM technology is widely considered a gold standard for high sensitivity molecular testing and continues to be one of the most sensitive dPCR approaches.

SafeSEQ technology demonstrates ultra-sensitive detection of low-frequency mutations, with a calling threshold of 5 mutant molecules (0.025% mutant allele frequency [MAF]) from whole blood. Concordance analysis of SafeSEQ and OncoBEAM results demonstrated an overall percent agreement of 99.6% for detection of mutations in EGFR, KRAS, and BRAF (>0.1% MAF).

The 5-year survival rate for metastatic NSCLC (mNSCLC) patients is relatively low; however, it has improved with the advent of targeted therapies and uptake of circulating tumor DNA (ctDNA) based technologies in recent years. In groundbreaking NSCLC clinical trials AURA and TIGER-X, patients positive for EGFR T790M detected in plasma by OncoBEAM had equivalent outcomes to patients positive by a tissue-based assay when treated with third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), which have demonstrated potent activity against first-line EGFR TKI resistance mediated by EGFR T790M.

SafeSEQ NSCLC testing delivers broader genomic coverage than OncoBEAM, with the same ultra-sensitive detection for rare mutant molecules. Therefore, SafeSEQ is better suited to identify molecular mediators of treatment resistance to improve therapeutic strategies, delivering high-resolution monitoring of therapeutic efficacy, and enabling minimum residual disease (MRD) detection and recurrence surveillance for NSCLC patients.

Poster number LB053, "Clinical evaluation of NGS-based liquid biopsy genotyping in non-small cell lung cancer (NSCLC) patients," presented by Hillary Sloane, Associate Director of Medical & Scientific Affairs at Sysmex Inostics, will be available Saturday, April 10, 2021, from 8:30 AM – 11:59 PM EDT during the 112th Annual Meeting of the American Association for Cancer Research (AACR) (Free AACR Whitepaper) during Session PO.CL11.04 – Liquid Biopsies: Circulating DNA.

On April 10, 2021 iTeos Therapeutics, Inc. (Nasdaq: ITOS), clinical-stage biopharmaceutical company pioneering the discovery and development of a new generation of highly differentiated immuno-oncology therapeutics for patients, reported a presentation featuring preliminary clinical data from 22 adult patients in the ongoing Phase 1/2a trial of its anti-TIGIT antibody, EOS-448, at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2021, taking place virtually April 10-15 (Press release, iTeos Therapeutics, APR 10, 2021, View Source [SID1234577846]). The presentation highlights initial findings from the completed dose escalation monotherapy portion of the trial, indicating a favorable tolerability profile and early signs of clinical activity in advanced cancers.

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"We are pleased to share these data showing promising preliminary signs of clinical activity and a favorable tolerability profile with our anti-TIGIT antibody, EOS-448, in patients with advanced cancers," said Joanne Jenkins Lager, M.D., chief medical officer of iTeos Therapeutics. "The results support our excitement around TIGIT as a therapeutic target capable of harnessing the immune system to treat patients with advanced, difficult to treat cancers. We believe the depletion of TIGIT+ suppressive and exhausted cells shown at even the lowest tested dose provides evidence of engagement of the FcγR, and therefore the potential of EOS-448 to activate multiple immune mechanisms. Based on these encouraging results, we are enrolling a total of 40 patients in this study to evaluate the effects of EOS-448 within the tumor. We are advancing EOS-448 into the next stage of clinical development as both a monotherapy and in combination for the treatment of multiple indications, with the goal of improving outcomes for people with advanced cancers."

Summary of the Data Presented

The objective of the dose escalation portion of the ongoing EOS-448 trial, presented at AACR (Free AACR Whitepaper), is to evaluate primary objectives of safety and tolerability, and secondary objectives of pharmacokinetics (PK), pharmacodynamics (PD), and antitumor activity of EOS-448 as a monotherapy in patients with advanced solid tumor cancers. As of the data cut-off (December 31, 2020), the trial had enrolled 22 advanced cancer patients with solid tumors for whom no standard treatment was available. The patients received EOS-448 intravenously (IV) once every two weeks (Q2W) or once every four weeks (Q4W) according to their dose and schedule allocation. Doses of 20, 70, 200, 700 mg Q2W and 1400 mg Q4W were evaluated. Since the data cut-off for the AACR (Free AACR Whitepaper) poster, as of March 9, 2021, an additional 11 patients have received single agent EOS-448. In addition to the five dose levels which were described at AACR (Free AACR Whitepaper), patients have also received doses of 400mg Q4w and 700mg Q4w.

EOS-448 was generally well-tolerated at all tested doses in patients with advanced cancer. Preliminary evidence of clinical activity as a monotherapy, including a confirmed partial response in one pembrolizumab-refractory melanoma patient and disease stabilization in nine patients, was also observed. The most common treatment related adverse events were itching, infusion-related reactions, fatigue, rash and fever, and one treatment related serious adverse event, a grade 2 systemic inflammatory response, was observed. As of March 9, 2020, two additional treatment-related serious events have been reported: Grade 2 Systemic Inflammatory Response and Grade 3 infusion-related reaction.

PK assessments indicated a linear and dose-proportional response and PD assessments showed complete target engagement. Biomarker analyses showed evidence of FcγR engagement, as demonstrated by a reduction in suppressive immune cells and immune cells considered to be exhausted in the blood, including TIGIT+ regulatory T cells (Tregs) and TIGIT+ CD8 T cells, with only a slight reduction in the total CD8+ T cell count. A shift towards a more functional immune response was observed, with a two-fold increase in the ratio of CD8+ T cells to Treg and a four-fold increase in the ratio of CD8+ TIGIT- T cells to CD8+ TIGIT+ T cells.

"I am highly encouraged by these initial results from the EOS-448 trial, particularly the clinically meaningful response to treatment in the pembrolizumab-refractory melanoma patient," said Mario Sznol, M.D., professor of medicine and leader, Melanoma/RCC Disease-Associated Research Team, at Yale University. "The treatment of patients who develop resistance to checkpoint inhibitors is challenging in a number of tumor types, and these data give us hope that EOS-448 could provide benefit in adult solid tumor patients who don’t respond to or who progress on current checkpoint inhibitors."

The e-poster and abstract can be accessed on the AACR (Free AACR Whitepaper) conference website. The abstract and presentation details are as follows:

Title: Preliminary data from Phase I first-in-human study of EOS884448, a novel potent anti-TIGIT antibody, monotherapy shows favorable tolerability profile and early signs of clinical activity in immune-resistant advanced cancer
Session: Phase I Clinical Trials
Poster #: CT118
Authors: Tom Van den Mooter, et al.

The Company will host a conference call and webcast to provide an overview of the data on Monday, April 12 at 8:00 a.m. EDT. Details are as follows:

Participant Dial-In: (833) 607-1661
International Dial-In: (914) 987-7874
Conference ID: 2888301
Webcast: View Source

The abstract was posted online at 12:01 a.m. EDT on Friday, April 9 and the e-poster launched at 8:30 a.m. EDT on Saturday, April 10 on the AACR (Free AACR Whitepaper) conference website.

EOS-448 Further Clinical Development Plans
Based on these preliminary results, the Company plans to advance EOS-448 using combination trials in both checkpoint-naïve and resistant patients. These Phase 1b trials will assess the safety of EOS-448 in combination with pembrolizumab and in combination with iTeos novel agent inupadenant in patients with solid tumors, and as a monotherapy and in combination with an Immunomodulatory Drug (IMiD) in patients with multiple myeloma. Subsequent disease-specific Phase 2a trials are planned in patients with non-small cell lung cancer, head and neck cancer, melanoma, and myeloma. The Company is also planning for later-stage trials of EOS-448, including in combination with pembrolizumab.

On April 10, 2021 Synthekine Inc., an engineered cytokine therapeutics company, reported preclinical data presented at the American Association of Cancer Research Annual Meeting 2021 demonstrating its alpha/beta selective IL-2 partial agonist, STK-012, induced potent anti-tumor activity while avoiding the toxicities that have hindered the development of IL-2 therapeutics, including vascular leak syndrome (VLS) (Press release, Synthekine, APR 10, 2021, View Source [SID1234577862]). Synthekine also presented new data on its orthogonal IL-2 and CD-19 CAR-T system (STK-009 and SYNCAR-001).

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"IL-2 offers a wealth of therapeutic promises and challenges. While wild-type IL-2 is a potent T-cell stimulator and has shown single agent activity in late-stage cancers, its broad and non-specific activation leads to critical, dose-limiting toxicities," said Martin Oft, M.D., chief development officer at Synthekine. "We believe that the efficacy of IL-2 is driven by the proliferation and activation of antigen activated T cells, while the toxicity of IL-2 is driven by its broad and non-specific proliferation, extravasation, and activation of all lymphocytes, including NK cells and naïve T cells. We have designed our alpha/beta IL-2 to selectively bias towards antigen activated T-cells and avoid NK cells and naïve T cells, a new approach designed to improve on both the efficacy and the toxicity of wild-type IL-2. STK-012 demonstrates improved therapeutic index compared to wild-type IL-2 and a non-alpha comparator. We look forward to advancing this program to an IND filing in 2021."

Efficacy of STK-012 was evaluated in multiple mouse models using a mouse surrogate of STK-012 (alpha/beta IL-2). In these studies, the alpha/beta IL-2 achieved superior efficacy in control of tumor growth and rate of complete responses compared to both wild-type IL-2 and a non-alpha IL-2. Synthekine’s alpha/beta IL-2 was significantly more effective than these comparators at increasing intratumoral CD8+ T-cells, including the ratio of CD8 T cells to Tregs. Importantly, studies showed the alpha/beta IL-2 did not induce lethality or VLS at therapeutic or supratherapeutic doses. Both wild-type and non-alpha IL-2 showed vascular toxicity, including VLS and lethality in mice. This finding was also supported by data from non-human primates, with the comparators resulting in significantly more infiltration of inflammatory cells in the lung relative to STK-012.

Synthekine also presented new data on its orthogonal IL-2 and CD-19 CAR-T system (STK-009 and SYNCAR-001). New analyses further demonstrate STK-009 upregulates markers for expansion and activation of SYNCAR-001 cells in a CAR refractory lymphoma model and confers a gene signature indicative of long-term memory T cell development.