On April 12, 2022 PerkinElmer, Inc. (NYSE: PKI), a global leader committed to innovating for a healthier world, reported that the Company will release its first quarter 2022 financial results after market close on Tuesday, May 3, 2022 (Press release, PerkinElmer, APR 12, 2022, View Source [SID1234612069]). The Company will host a conference call the same day at 5:00 p.m. ET to discuss these results. Prahlad Singh, president and chief executive officer, and Jamey Mock, senior vice president and chief financial officer, will host the conference call.

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To access the call, a live audio webcast will be available via this registration form or on the Investors section of the Company’s website.

A replay of the webcast will be available beginning at 7:00 p.m. ET, Tuesday, May 3, 2022 through the Investors section of the Company’s website.

On April 12, 2022 Pathios Therapeutics Limited ("Pathios"), a biotech company focused on the development of first-in-class therapies for cancer, reported that new data on PTT-3213, the company’s orally bioavailable, potent and selective GPR65 inhibitor, were reported in a podium presentation at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2022 (Press release, Pathios Therapeutics, APR 12, 2022, View Source [SID1234612068]). Presented findings from human genetic and ex vivo human cellular studies demonstrated that GPR65, a pH-sensing, G protein-coupled receptor, serves as a critical innate immune checkpoint in the human tumor microenvironment. Furthermore, data showed that inhibition of GPR65 with PTT-3213 resulted in significantly reduced tumor growth in the MC38 mouse syngeneic cancer model. The AACR (Free AACR Whitepaper) conference is being held April 8-13, 2022 in New Orleans, Louisiana.

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Stuart Hughes, Ph.D., Pathios’ chief executive officer, delivered the podium presentation as part of the conference’s "Cancer Biology and Tumor Immunity" mini-symposium. The key findings presented included:

In response to acidic pH, human macrophages undergo profound alterations in gene expression that render them indistinguishable from a typical immunosuppressive tumor associated macrophage. Pathios’ small molecule GPR65 inhibitors are able to fully counteract this polarization and re-establish an anti-tumorigenic phenotype
In vivo studies in the MC38 colon cancer syngeneic mouse model demonstrated that once weekly oral dosing with PTT-32131 provided equivalent efficacy to dosing twice weekly with a murine anti-PD-1 antibody
The combination of PTT-3213 and anti-PD-1 therapy provided greater efficacy than either agent gave alone in the MC38 colon cancer syngeneic mouse model
Inhibition of GPR65 by PTT-3213 was associated with significant increases in tumor-infiltrating CD8+ T cells and natural killer T (NKT) cells, both cell types with critical tumor cell killing capabilities. There was a clear correlation between the increased infiltration of these cells and decreased tumor volume across combination groups
"These are powerful findings as they firmly demonstrate the substantial clinical promise of GPR65 inhibition as a novel immuno-oncology strategy in a range of solid cancers. Importantly, these data further validate our long-held view that low pH acting on GPR65 is a critical innate immune checkpoint and the key determinant of immunosuppressive myeloid cells in the tumor microenvironment," commented Dr. Hughes. "As highlighted during our AACR (Free AACR Whitepaper) presentation, we have now assembled a robust collection of data on the associations between the human genetics of GPR65 and cancer outcomes, including ex vivo studies in human cells. Additionally, we have now shown that weekly dosing of a small molecule GPR65 inhibitor is able to provide equivalent efficacy to anti-PD-1. We look forward to continuing research into this novel immuno-oncology target as we build on this data and complete further candidate nomination studies through 2022."

About Acidity in the Tumor Microenvironment

The acidic tumor microenvironment, inherent to many cancers, causes a profound immunosuppression of infiltrating immune cells. This environment disarms the anti-cancer immune response and negates the effectiveness of current immunotherapies. This is particularly evident in tumor associated macrophages (TAM), where acidity is sensed by the cell-surface receptor GPR65, leading to an induction of the transcriptional repressor ICER (inducible cAMP early repressor) and the widespread suppression of a host of pro-inflammatory mediators and anti-tumorigenic genes.

On April 12, 2022 Panbela Therapeutics, Inc. (Nasdaq: PBLA), a clinical stage biopharmaceutical company developing disruptive therapeutics for the treatment of patients with cancer reported a poster presentation highlighting the results for SBP-101 as a polyamine metabolism modulator in ovarian cancer at the American Association for Cancer Research (AACR) (Free AACR Whitepaper), taking place April 8-13, 2022 (Press release, Panbela Therapeutics, APR 12, 2022, View Source;utm_medium=rss&utm_campaign=panbela-announces-poster-presentation-at-american-association-for-cancer-research [SID1234612067]). The work reflects the Company’s ongoing collaboration with Johns Hopkins University School of Medicine.

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"The treatment of C57Bl/6 mice injected with VDID8+ ovarian cancer with SBP-101 was observed to significantly prolong survival and decrease overall tumor burden," said Jennifer K. Simpson, PhD, MSN, CRNP, President & Chief Executive Officer of Panbela. "We are grateful to our collaborators at Johns Hopkins University School of Medicine, who are on the leading edge of cancer research. This data supports our efforts to initiate an ovarian cancer program this year. Additionally, we are excited to review these results on an R&D call planned for May 3, 9:00 AM EST."

"The results suggest that SBP-101 may have a role in the clinical management of ovarian cancer," said Dr. Simpson, "We look forward to continuing our studies in ovarian, and other cancers, to develop effective therapeutics for patients with unmet medical needs."

The poster highlights the role of naturally occurring polyamines, putrescine, spermidine and spermine, as essential for cellular growth and proliferation. As such, many cancers are reliant on elevated polyamine levels that are maintained through dysregulated polyamine metabolism. Polyamine metabolism is thus a promising target for cancer therapeutics, and modulation of polyamine metabolism has been attempted with numerous enzyme inhibitors and polyamine analogues. SBP-101 (diethyl dihydroxyhomospermine) is a novel spermine analogue that has shown efficacy in slowing pancreatic tumor progression both in vitro and in vivo.

This study determined the effect of SBP-101 treatment on polyamine metabolism in a variety of cancer cell types in vitro including lung, ovarian, prostate, pancreatic and breast. In addition, the activity of four enzymes involved in the polyamine pathway following treatment with either SBP-101 or the well-characterized spermine analogue, BENSpm (N1,N11-bisethylnorspermine) was evaluated. These results indicate that SBP-101 likely exerts its effects predominately through decreased polyamine biosynthesis with minor upregulation of catabolism, in contrast to the structurally similar BENSpm where the increase in polyamine catabolism is the predominant response.

The efficacy of SBP-101 utilizing the VDID8+ murine ovarian cancer model (ID8+ C57Bl/6 ovarian cells overexpressing both VEGF and Defensin) was evaluated. The mice were treated with SBP-101 at either 24 mg/kg or 6 mg/kg alternating MWF. Both doses of SBP-101 produced a statistically significant prolongation of survival (24mg/kg p=.0049, 6 mg/kg p=.0042). There was no significant difference in response between the two SBP-101 doses. The prolonged survival was correlated with a delay in the production of ascites, the indication of tumor burden in this model. Additionally, when SBP-101 treated mice succumbed to the disease, their overall tumor burden was lower when compared to control mice.

The poster concludes that the treatment of C57Bl/6 mice injected with VDID8+ ovarian cancer with SBP-101 significantly prolonged survival and decreased overall tumor burden. Future studies will be designed to evaluate the effects of SBP-101 in combination with other polyamine metabolism modulators as well as with immune modulators.

Details of the presentation are as follows:

Poster Presentation

Title: The potential of spermine analogue SBP-101 (diethyl dihydroxyhomospermine) as a polyamine metabolism modulator in ovarian cancer
Session Category: Experimental and Molecular Therapeutics
Session Title: Small Molecule Therapeutic Agents Abstract #: 5488

Additional meeting information can be found on the AACR (Free AACR Whitepaper) website: Abstracts | AACR (Free AACR Whitepaper) Annual Meeting 2022 | April 8-13, 2022 | New Orleans

The poster will also be available on the Company’s website at View Source .

About SBP-101

SBP-101 is a proprietary polyamine analogue designed to induce polyamine metabolic inhibition (PMI) by exploiting an observed high affinity of the compound for pancreatic ductal adenocarcinoma and other tumors. The molecule has shown signals of tumor growth inhibition in clinical studies of US and Australian metastatic pancreatic cancer patients, demonstrating a median overall survival (OS) of 12.0 months which is not yet final, and an objective response rate (ORR) of 48%, both exceeding what is seen typically with the standard of care of gemcitabine + nab-paclitaxel suggesting potential complementary activity with the existing FDA-approved standard chemotherapy regimen. In data evaluated from clinical studies to date, SBP-101 has not shown exacerbation of bone marrow suppression and peripheral neuropathy, which can be chemotherapy-related adverse events. Serious visual adverse events have been evaluated and patients with a history of retinopathy or at risk of retinal detachment will be excluded from future SBP-101 studies. The safety data and PMI profile observed in the current Panbela sponsored clinical trial provides support for continued evaluation of SBP-101 in a randomized clinical trial. For more information, please visit View Source .

On April 12, 2022 ORIC Pharmaceuticals, Inc. (Nasdaq: ORIC), a clinical stage oncology company focused on developing treatments that address mechanisms of therapeutic resistance, reported that three preclinical poster presentations and one preclinical oral presentation at the 2022 American Cancer Research Association (AACR) (Free AACR Whitepaper) Annual Meeting (Press release, ORIC Pharmaceuticals, APR 12, 2022, View Source [SID1234612066]).

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"Our four presentations at AACR (Free AACR Whitepaper) reflect the broad and diverse pipeline of differentiated programs at ORIC," said Jacob M. Chacko, MD, chief executive officer. "Preclinical data further demonstrate the potential of CD73 inhibitor ORIC-533 as a treatment for multiple myeloma, as well as the compelling brain penetrant properties of ORIC-114 with its high potency against exon 20 insertion mutations. We also introduced our highly selective inhibitors of PLK4 as a potential treatment for breast cancer by leveraging a synthetic lethal liability. We look forward to the continued advancement of these programs as well as ORIC-944, with initial data for our three clinical programs expected in the first half of 2023."

Presentation details:

ORIC-533: CD73 Inhibitor
ORIC-533 is a highly potent, orally bioavailable small molecule inhibitor of CD73 that has demonstrated more potent adenosine inhibition in preclinical studies compared to an antibody approach and other small molecule inhibitors of the adenosine pathway and is currently being studied in a Phase1b trial in multiple myeloma.

Poster Presentation:
ORIC-533, a small molecule CD73 inhibitor with best-in-class properties, reverses immunosuppression and has potential as an immunomodulatory therapy in patients with multiple

Oral Presentation:
Optimizations leading to ORIC-533: A potent orally bioavailable CD73 inhibitor that restores anti-tumor immunity in high AMP environments

Key findings of the presentations:

Target candidate profile for best-in-class CD73 inhibitor was met by ORIC-533 in preclinical analyses.
In an autologous ex vivo assay using bone marrow aspirates from patients with relapsed or refractory multiple myeloma, CD73 inhibition stimulated plasmacytoid dendritic cells and activated T cells.
ORIC-533, across multiple dose levels, overcame immune suppression and triggered significant lysis and cell death of multiple myeloma cells in an assay comprised of autologous bone marrow microenvironment.
These results demonstrate that single agent ORIC-533 potently inhibits the adenosine pathway, which restores anti-tumor immunity and therefore holds potential as a treatment for patients with multiple myeloma.
ORIC-114: EGFR/HER2 Inhibitor
ORIC-114 is a brain penetrant, orally bioavailable, irreversible inhibitor designed to selectively target EGFR and HER2 with high potency against exon 20 insertion mutations, and is currently being studied in a Phase 1b trial in patients with advanced solid tumors with EGFR or HER2 exon 20 alterations or HER2 amplifications.

Poster Presentation:
ORIC-114, an orally bioavailable, irreversible kinase inhibitor, has superior brain penetration and antitumor activity in subcutaneous and intracranial NSCLC models

Key findings of the presentation:

Oral administration of ORIC-114 resulted in tumor regressions in an EGFR exon 20 NSCLC model, with superior efficacy relative to CLN-081 and BDTX-189.
Additional preclinical studies confirmed the brain-penetrance and free unbound exposure in the CNS, which translated to greater anti-tumor activity compared to mobocertinib (TAK-788) in an intracranial NSCLC model.
These data confirm ORIC-114 as a potent, selective, irreversible, brain penetrant EGFR exon 20 inhibitor, and a promising therapeutic candidate, including for patients with CNS metastases.
PLK4 Inhibitor Program:
The PLK4 Inhibitor program is a small molecule therapeutic program intended to address a mechanism of innate resistance found in a subset of breast cancers, specifically a synthetic lethal interaction of polo-like kinase 4 (PLK4) inhibition in tumors bearing a TRIM37 DNA amplification.

Poster Presentation:
Discovery of novel, highly selective inhibitors of PLK4 that demonstrate in vivo regressions in TRIM37 high xenografts

Key findings of the presentation:

ORIC discovered novel, potent, orally bioavailable small molecule inhibitors of PLK4 that are highly selective, including against the closely related aurora kinases and PLK1-3.
Cell viability assessment across a cancer cell line panel revealed that the highly selective ORIC PLK4 inhibitors showed greater potency in TRIM37 high cancer cell lines as compared to TRIM37 low cell lines.
Importantly, cell potency in TRIM37 high cancer cells was rescued with knockdown of TRIM37, illustrating that selective PLK4 inhibitors exhibit synthetic lethality with TRIM37 amplification.
Oral administration of ORIC PLK4 inhibitors resulted in strong anti-tumor activity of TRIM37 high xenograft tumors, with corresponding pharmacodynamic effects and no body weight loss.

On April 12, 2022 OncoNano Medicine, Inc. reported positive results from the company’s ON-BOARD pH-sensitive nanoparticle platform (Press release, OncoNano Medicine, APR 12, 2022, View Source [SID1234612065]). The data, presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2022, demonstrate that the clinically validated ON-BOARD platform has the potential to be a universal tool for tumor specific activation and the efficient delivery of proteins for an improved therapeutic index .

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"Our ON-BOARD micelle platform is designed to efficiently carry a broad range of payloads to the tumor microenvironment. Capable of being tuned to deliver either small molecules or biologics, the ON-BOARD platform has the potential to be a universal tool for targeted delivery of therapeutics to a range of cancers," said Tian Zhao, Ph.D., Vice President of Research & Development for OncoNano Medicine, Inc. "We are pleased with the positive data from our research efforts to encapsulate therapeutic antibodies with our ON-BOARD delivery technology and look forward to the further development of protein payloads with an improved therapeutic index."

A variety of biosimilar monoclonal antibodies including those of atezolizumab, cetuximab, pembrolizumab, trastuzumab and ipilimumab were encapsulated by the ON-BOARD platform.
The findings indicate that ON-BOARD demonstrated:
• Encapsulation of antibodies without additional modification of the original antibody
• Encapsulation efficiency ranging from 50-100%
• Formulations characterized as uniformly distributed particles < 100nm in size with good stability
• Over a 100-fold activation window between the acid-activated and intact formulations based on in vitro assessment by cell-based reporter assays
• pH-dependent activation that was further confirmed by affinity and binding assay
• Tumor specific accumulation that was demonstrated by a biodistribution study

Presentation Overview

TITLE: Encapsulating therapeutic antibodies for tumor specific activation and delivery using a clinically validated pH-sensitive nanoparticle platform

PRESENTER: Jason Miller, Ph.D., Associate Director, Research Pipeline Development, OncoNano Medicine