On April 10, 2021 Phio Pharmaceuticals Corp. (Nasdaq: PHIO), a biotechnology company developing the next generation of immuno-oncology therapeutics based on its proprietary self-delivering RNAi (INTASYL) therapeutic platform, reported new in vivo data showing intratumoral (IT) treatment with the murine PD-1 targeting INTASYL (mPH-762) inhibits tumor growth in a dose dependent fashion in PD-1 responsive and refractory models (Press release, Phio Pharmaceuticals, APR 10, 2021, View Source [SID1234577828]). Furthermore, on target efficacy was supported by modulation of immune cell populations toward antitumor phenotypes. The Company believes these data further support the potential for INTASYL mPH-762 to provide strong local immune checkpoint blockade (ICB), without the dose immune-related adverse effects (irAEs) seen with systemic ICB antibody therapy. Phio is planning to advance this program with a first-in-human clinical study of PH-762 as a directly administered drug in patients with advanced melanoma at the Gustave Roussy Institute, which is scheduled to be initiated in the fourth quarter of 2021.

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"We are pleased to announce new in vivo data today that show INTASYL mPH-762 offered strong tumor control in Hepa 1-6 and CT26 models, which are PD-1 responsive and PD-1 refractory models, respectively. The modulation of key immune cell populations in the tumor microenvironment (TME) by local application of INTASYL mPH-762 provides further evidence that the desired efficacy to treat these cancers can be attained by direct intratumoral administration. Such local administration can have several advantages such as avoiding dose limiting systemic side effects which are often dose-limiting," stated Dr. Simon Fricker, Phio’s VP of Research. "These data further support our excitement around this asset and to bring PH-762 to patients, starting with our first clinical study later this year."

All INTASYL treatments were well tolerated. Treatment with mPH-762 inhibited tumor growth in both CT26 and Hepa 1-6 models in a dose dependent manner compared to control treated tumors, with mPH-762 providing tumor growth inhibition analogous to systemic anti-PD-1 monoclonal antibody (mAb) use. Hepa 1-6 is a PD-1 inhibition-responsive hepatoma model and CT26 is a PD-1 inhibition-refractory colon cancer model. Dose-correlating on-target silencing of PD-1 protein expression across key TME cell populations was observed under treatment with mPH-762, but not with anti-PD-1 mAb. The modulation of tumor immune cell populations toward antitumor phenotypes, supporting on target efficacy, included significantly increasing overall %CD45+ and %NK1.1+ / CD45+ populations and increasing median M1 (immunostimulatory) / M2 (immunosuppressive) polarized tumor associated macrophage ratios.

These data were presented today during the AACR (Free AACR Whitepaper) Annual Meeting 2021 in a poster titled "Intratumoral INTASYL self-delivering RNAi targeting PD-1 provides in vivo tumor control and mechanistic modulation of tumor microenvironment analogous to that of systemic anti-PD-1 antibody". An archived version of the poster presentation will be made available on the "Investors – Events and Presentations" section of the Company’s website (click here).

On April 10, 2021 Cardiff Oncology, Inc. (Nasdaq: CRDF), a clinical-stage biotechnology company developing onvansertib to treat cancers with the greatest medical need for new treatment options, including KRAS-mutated colorectal cancer, pancreatic cancer, and castrate-resistant prostate cancer, reported observations from its Expanded Access Program (EAP) of onvansertib in KRAS-mutated metastatic colorectal cancer (mCRC), featured in a virtual oral poster presentation at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2021 (Press release, Cardiff Oncology, APR 10, 2021, View Source [SID1234577845]).

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Cardiff Oncology’s EAP has enrolled participants who failed or progressed on multiple lines of standard-of-care treatment and uses the same combination regimen (onvansertib 15 mg/m2 + FOLFIRI/bevacizumab) and dosing schedule as the Company’s ongoing Phase 1b/2 mCRC clinical trial. The median progression free survival (mPFS) of evaluable participants in the EAP is 5.6 months to-date, which represents an increase over the 2-3 months mPFS of historical controls1. 62.5% of participants had a greater than 50% decrease in KRAS MAF after one cycle of treatment and continue to show a durable response, having not yet reached the mPFS. Onvansertib has been well tolerated with no serious adverse events (SAEs) reported as of the AACR (Free AACR Whitepaper) cutoff date.

"The mPFS observed thus far is significantly better than what is expected and shows promise for improving overall prognosis in this patient population," said Dr. Manish R. Sharma, associate director of clinical research at START Midwest. "The Expanded Access Program has provided access to onvansertib for mCRC patients who are heavily pretreated and thus do not meet the stringent second line eligibility criteria for enrollment in Cardiff Oncology’s ongoing Phase 2 clinical trial."

Dr. Mark Erlander, chief executive officer of Cardiff Oncology added, "We are very pleased to provide access to onvansertib for mCRC patients with the greatest need for a new treatment option. It’s particularly gratifying to see many EAP participants benefit clinically from the addition of onvansertib to standard-of-care and improve from having progressive to stable disease or better."

Highlights from the AACR (Free AACR Whitepaper) presentation include:

Baseline Characteristics of Evaluable Patients (n = 20):

Evaluable participants received a median of 3 prior lines of therapy (range: 1-6)
15 of 20 (75%) evaluable participants received an irinotecan-based regimen as their last therapy prior to enrolling in the EAP
13 of 20 (65%) evaluable participants were progressing prior to enrolling in the EAP
Clinical Benefit:

Evaluable participants had a mPFS of 5.6 months (95% confidence interval: 2.7 months – median PFS not reached)
11 of 20 of participants evaluable for clinical benefit remain on treatment as of the AACR (Free AACR Whitepaper) cutoff date
Biomarker:

16 of 20 (80%) evaluable participants had a KRAS variant detected by droplet digital PCR (ddPCR) before beginning onvansertib treatment in the EAP
Participants with a greater than 50% decrease in KRAS MAF (n=10) after one treatment cycle had a significant increase in PFS (mPFS not reached) compared to participants who had a decrease in KRAS MAF of less than 50% (n = 6; mPFS of 2.6 months)
Tolerability:

Onvansertib in combination with FOLFIRI/bevacizumab has been well tolerated with no SAEs reported in participants as of the AACR (Free AACR Whitepaper) cutoff date
The virtual poster, "Expanded access program of the PLK1 inhibitor onvansertib for treatment of patients with KRAS-mutant metastatic colorectal cancer" is available for on-demand viewing on the AACR (Free AACR Whitepaper) Annual Meeting 2021 e-poster website and is also posted on the "Scientific Presentations" section of the Cardiff Oncology website at View Source

References

Bekaii-Saab et al., Clin. Colorectal Cancer, 2019
About the EAP for Onvansertib in KRAS-mutated mCRC

Sometimes called "compassionate use", expanded access is a potential pathway for a patient with a serious or life-threatening disease to gain access to an investigational drug for treatment outside of a clinical trial, particularly when no comparable or satisfactory alternative therapy options are available. The Cardiff Oncology EAP in KRAS-mutated mCRC is using the same combination treatment regimen (onvansertib 15 mg/m2 + FOLFIRI and bevacizumab) and dosing schedule as the ongoing Phase 1b/2 clinical trial and is intended for patients that have progressed on prior therapy and do not meet the second line eligibility criteria for enrollment in the clinical trial. The program has reached capacity and is no longer open to enrollment.

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.