On October 7, 2021 ORIC Pharmaceuticals, Inc. (Nasdaq: ORIC), a clinical stage oncology company focused on developing treatments that address mechanisms of therapeutic resistance, reported multiple presentations, including initial clinical data from an ongoing Phase 1b study evaluating ORIC-101, a glucocorticoid receptor antagonist, in combination with enzalutamide, in patients with metastatic prostate cancer progressing on enzalutamide (Press release, ORIC Pharmaceuticals, OCT 7, 2021, View Source [SID1234590917]). The abstracts and presentations are available for on-demand viewing via the online platform for AACR (Free AACR Whitepaper)-NCI-EORTC as of October 7, 2021, at 9 a.m. ET.

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Presentations:

Initial results from a Phase 1b study of ORIC-101, a glucocorticoid receptor antagonist, in combination with enzalutamide in patients with metastatic prostate cancer
Biomarker results supporting selection of RP2D from a Phase 1b study of ORIC-101, a glucocorticoid receptor antagonist, in combination with enzalutamide in patients with metastatic prostate cancer progressing on enzalutamide
ORIC-114, an orally bioavailable, irreversible kinase inhibitor, has superior brain penetrant properties and enhanced potency in preclinical studies of HER2-positive breast cancer
"We are pleased to share initial data from our ORIC-101 clinical program in patients with metastatic prostate cancer. The combination was well tolerated without evidence of drug-drug interaction affecting enzalutamide dosing and has demonstrated preliminary evidence of antitumor activity in the relevant patient population," said Pratik S. Multani, MD, chief medical officer. "Given the tumor heterogeneity in metastatic prostate cancer, we’ve made significant progress in identifying a key patient population that may benefit from ORIC-101 and, within these patients, seen preliminary evidence of more pronounced clinical benefit in patients whose tumors express higher GR levels. Patients are continuing to enroll in the expansion cohort and we look forward to reporting an update from the Phase 1b trial in 2022."

ORIC-101: Glucocorticoid Receptor (GR) Antagonist

The Phase 1b clinical trial of ORIC-101 in combination with enzalutamide is a single arm, multicenter, open-label study conducted in two parts, intended to establish the recommended Phase 2 dose (RP2D), safety, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity when administered in patients with metastatic prostate cancer progressing on enzalutamide.

In the Part I dose escalation portion of the trial, three cohorts of patients were enrolled to evaluate daily dosing of ORIC-101 with doses ranging from 80 to 240 mg, in combination with 160 mg of enzalutamide once daily dosing. Following the completion of the dose escalation portion of the study, the RP2D was determined to be 240 mg of ORIC-101 and 160 mg of enzalutamide once daily.

In the Part II dose expansion portion of the trial, up to 48 patients with metastatic prostate cancer progressing on enzalutamide are expected to be enrolled and treated with the combination at the RP2D. Patients are enrolled independent of GR status, with retrospective analysis of GR expression and other potentially predictive biomarkers. Enrollment continues in the Part II dose expansion cohorts at nine clinical sites across the United States.

As of the August 20, 2021, data cut-off date:

Preliminary Safety Analyses:

25 patients were enrolled across Parts I/II of the study, which included 7 patients treated at non-RP2D doses and 18 patients treated at the RP2D of 240 mg of ORIC-101 and 160 mg of enzalutamide once daily.
RP2D was well tolerated; treatment-related adverse events were primarily Grade 1 or 2, with only four Grade 3 events, which all resolved with dose interruption.
Tolerability profile for the combination was generally consistent with that of single agent enzalutamide.
Preliminary PK Analysis:

Plasma concentrations exceeded the threshold for GR inhibition at all dose levels.
ORIC-101 exposure increased with dose.
No evidence observed of drug-drug interaction impacting enzalutamide levels.
Preliminary Biomarker Analyses:

GR pathway suppression, evaluated using GR target gene expression, was observed after one dose of ORIC-101 in peripheral blood mononuclear cells from 22 of 23 patients.
Moderate to high GR expression (IHC H-score ≥ 100) in prostate tumor cells was observed in 76% of pretreatment biopsies.
Translational efforts identified a key patient population, in line with published literature, consisting of the ~60% of patients with tumors lacking biomarkers of AR resistance (e.g., ARv7 splice variant, AR L702H point mutation) and AR independence (e.g., lineage switching).
Preliminary Antitumor Activity:

Within the key patient population (n=8), 75% (6 of 8) of patients’ tumors expressed moderate to high GR and 25% (2 of 8) of patients’ tumors expressed low GR.
The two patients with low GR came off treatment at less than two months. In contrast, the six patients with moderate to high GR demonstrated prolonged time on treatment (with two patients on treatment for over seven months, and another four patients still ongoing at varying durations at the time of the data cut).
ORIC-101 is also being evaluated in a Phase 1b trial in combination with nab-paclitaxel in up to 132 patients across four cohorts, including pancreatic ductal adenocarcinoma, ovarian cancer, triple negative breast cancer, and other advanced solid tumors. Enrollment continues in this study at 12 clinical sites across the United States and an additional update is expected in 2022.

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. These are the first publicly disclosed preclinical data with ORIC-114 demonstrating compelling activity in HER2-positive breast cancer models.

Key Findings of the Presentation:

ORIC-114 demonstrated greater cell potency on HER2-positive breast cancer cell lines relative to non-amplified cell lines and was more potent than lapatinib and tucatinib, two approved tyrosine kinase inhibitors for the treatment of HER2-positive breast cancer.
ORIC-114 demonstrated robust tumor regressions in a HER2-positive breast cancer in vivo model without significant body weight loss.
ORIC-114 demonstrated superior brain exposure compared to other EGFR exon 20 and HER2 targeted agents.
Separately, today the company disclosed head to head in vivo preclinical data in an EGFR exon 20 NSCLC xenograft model demonstrating good tolerability and improved efficacy, including a 90% complete response rate, versus multiple clinical stage exon 20 inhibitors.

Webcast and Conference Call

ORIC will host a conference call and webcast today at 9:00 a.m. ET. To participate in the conference call, please dial (833) 651-0991 (domestic) or (918) 922-6080 (international) and refer to conference ID 3575856. A live webcast and audio archive of the conference call will be available through the investor section of the company’s website at www.oricpharma.com. The webcast will be available for replay for 90 days following the presentation.

About ORIC-101

ORIC-101 is a potent and selective small molecule antagonist of the glucocorticoid receptor, which has been linked to resistance to multiple classes of cancer therapeutics across a variety of solid tumors. Preclinical in vitro and in vivo data suggest ORIC-101 is able to address key resistance mechanisms of multiple classes of cancer treatments, including taxanes and androgen receptor modulators. Based on preclinical and clinical studies, ORIC-101 is expected to have reduced drug-drug interaction liabilities than other glucocorticoid receptor antagonists. Currently, there are no glucocorticoid receptor antagonists approved by the FDA for the treatment of cancer. Following the successful completion of two Phase 1a trials in over 50 healthy volunteers, ORIC initiated two separate Phase 1b trials of ORIC-101 in combination with (1) Abraxane (nab-paclitaxel) in advanced or metastatic solid tumors and (2) Xtandi (enzalutamide) in metastatic prostate cancer.

On October 7, 2021 AffyImmune Therapeutics, Inc., a clinical stage biotechnology company developing and deploying its Tune & Track platform for the use of CAR T cells to treat solid tumors, reported the close of a $30 million Series A+ funding by ORI Capital (ORI) (Press release, AffyImmune Therapeutics, OCT 7, 2021, View Source [SID1234590916]). The Company’s "Tune & Track" platform finely tunes the affinity of CAR T cells to reduce toxicity and increase CAR T cell longevity while allowing in vivo monitoring through a proprietary tracking system.

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The funding will be used to advance the Phase 1 study of AffyImmune’s lead asset, AIC1000, for the treatment of anaplastic thyroid cancer and refractory poorly differentiated thyroid cancer. In addition, AffyImmune will be able to conduct IND-enabling efforts for two additional pipeline candidates, and fund select drug discovery activities. AffyImmune also plans to double its headcount in the next nine months, with a focus on expanding its in-house discovery and leadership teams.

"We are delighted to strengthen AffyImmune’s relationship with ORI with this additional financing," said AffyImmune President & COO Eric von Hofe, Ph.D. "ORI’s dedication to transformative science and deep industry knowledge have been invaluable to our company strategy and growth, and their latest investment highlights the potential of our cutting-edge Tune & Track platform to revolutionize the treatment of solid tumors across a variety of cancers."

"We’re excited to further our investment in AffyImmune, as existing CAR T therapies have not been able to treat solid tumors or have only been effective in a small number of solid cancer patients," said Simone Song, Founder and Senior Partner at ORI Capital and Chairperson of AffyImmune’s Board of Directors. "AffyImmune’s pioneering Tune & Track technology platform will address the critical challenges in CAR T drug development for solid tumors including toxicity, antigen loss, T cell exhaustion, tumor microenvironment, and T cell trafficking. The Tune & Track platform will be life-changing for cancer patients faced with a diagnosis of advanced solid tumors."

As part of the financing, Elaine Yang, Director at ORI Capital, will join the Board of Directors of AffyImmune. "I am excited for this new role and the opportunity to provide counsel and support during AffyImmune’s next phase of growth," said Ms. Yang. "AffyImmune is advancing a leading pipeline of affinity-tuned CAR T therapies to treat solid tumors based on its Tune and Track technology platform, and I look forward to working with their management team and Board," said Ms. Yang.

On October 7, 2021 Loxo Oncology at Lilly, a research and development group of Eli Lilly and Company (NYSE: LLY), reported that preclinical characterization data for two new agents, LOXO-783 and LOXO-435, will be presented at the 2021 AACR (Free AACR Whitepaper)-NCI-EORTC Virtual AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper), held October 7-10, 2021 (Press release, Eli Lilly, OCT 7, 2021, View Source [SID1234590915]). The data will be presented as part of the plenary session titled "New Drugs on the Horizon II" as well as in individual poster presentations.

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LOXO-783 is a potent, highly mutant-selective and brain-penetrant allosteric PI3Kα H1047R inhibitor that is designed to spare wild-type PI3Kα, other PI3K isoforms, and other kinases. LOXO-435 is a potent and highly isoform-selective FGFR3 inhibitor with preserved activity against FGFR3 gatekeeper resistance mutations. Investigational new drug applications (INDs) are planned for both programs in 2022.

"LOXO-783 and LOXO-435 each represent years of diligent work by our discovery teams to build molecules that meet exacting target product profiles. In the case of both PI3Kα H1047R-mutated cancers and FGFR3-mutated cancers, patients deserve medicines purpose-built to their disease biology and we believe that these molecules have the potential to markedly improve on the efficacy and tolerability of existing agents," said Jacob Van Naarden, chief executive officer of Loxo Oncology at Lilly and President of Lilly Oncology. "We look forward to filing INDs for both programs in 2022 and subsequently moving into the clinic."

Details on oral and poster presentations are below:

Presentation Title: Discovery of mutant-selective PI3Kα and isoform-selective FGFR3 inhibitors: Insights from the Loxo Oncology at Lilly Discovery Model
Presentation Date & Time: Saturday, October 9, 4:00 p.m. ET
Session: Plenary Session 6: New Drugs on the Horizon II
Presenter: David Hyman, M.D.

Poster Title: Preclinical characterization of LOXO-435 (LOX-24350), a potent and highly isoform-selective FGFR3 inhibitor
Abstract Number: 141
Available: Thursday, October 7, 9 a.m. ET
Presenter: Joshua Ballard

Poster Title: Preclinical characterization of LOXO-783 (LOX-22783), a highly potent, mutant-selective and brain-penetrant allosteric PI3Kα H1047R inhibitor
Abstract Number: 142
Available: Thursday, October 7, 9 a.m. ET
Presenter: Anke Klippel, Ph.D.

About Loxo Oncology at Lilly
Loxo Oncology at Lilly was created in December 2019, combining the Lilly Research Laboratories oncology organization and Loxo Oncology, which was acquired by Lilly in early 2019. Loxo Oncology at Lilly brings together the focus and spirit of a biotech with the scale and resources of large pharma, with the goal of rapidly delivering impactful new medicines for people with cancer. Our approach centers on creating new oncology medicines that unequivocally work early in clinical development and will matter to patients.

On October 7, 2021 PierianDx, the global leader in clinical genomics knowledge, reported that it will partner with Florida Cancer Specialists & Research Institute (FCS) to support expanded access to the highest quality genomic testing on solid tumors and hematologic malignancies and lymph nodes leveraging NGS technology (Press release, PierianDx, OCT 7, 2021, View Source [SID1234590914]). Under the partnership, FCS will locally analyze and interpret sequencing data generated with the Illumina TruSight Oncology 500 Research Use Only assay and the Invitae VariantPlex, LiquidPlex, and FusionPlex panels using PierianDx Clinical Genomic Workspace (CGW) to rapidly and accurately detect mutations and offer the best therapeutic options for patients.

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Historical approaches to precision medicine testing include centralized testing performed at large national laboratories where the laboratory typically has little-to-no interaction with the patient and limited treating physician interaction. By localizing genomic testing, FCS patients will benefit from more direct access to testing within the context of care. Offering these tests in the FCS laboratory will also enable improved collaboration between the diagnostic team who interpret the test results and the treating physicians, which drives alignment across the care team and increases confidence in the clinical utility of genomic testing.

The genomic test results at Florida Cancer Specialists will be delivered via a customizable report generated by the PierianDx CGW. Powered by a comprehensive knowledgebase and secure and scalable data analysis platform, the PierianDx CGW will enable Florida Cancer Specialists to quickly and accurately classify and interpret variants to inform treatment or match patients to the right trial within the practice’s large network of participating clinical trials.

According to Florida Cancer Specialists CEO Nathan H. Walcker, "We see tremendous clinical and strategic value to performing this very important testing in-house. By offering in-house genomic testing, we will continue to seek the best options for care for our patient population by quickly and efficiently providing existing treatments as well as optimizing clinical trial matching opportunities. We look forward to partnering with PierianDx to provide even greater tools to our physician partners at FCS and enabling wider access to high complexity testing to the patients we are privileged to serve."

"We are thrilled to provide our best-in-class bioinformatics and knowledge platform to support personalized, community-based cancer care," states Mark McDonough, CEO of PierianDx. "Partnering with leading-edge institutions like Florida Cancer Specialists aligns perfectly with our mission to democratize clinical genomics and to optimally serve physicians and the patients they treat."

On October 7, 2021 Crown Bioscience, a JSR Life Sciences company and leader in translational services that help biopharmaceutical companies accelerate new drug development programs, reported the launch of its ‘3D Ex Vivo Patient Tissue Platform’ (Press release, Crown Bioscience, OCT 7, 2021, View Source [SID1234590913]). Using freshly collected patient tumor material, this new service can accurately measure oncology and immuno-oncology drug-induced tumor killing and endogenous immune cell proliferation in a high throughput format. Researchers are presenting data on the new platform at this year’s AACR (Free AACR Whitepaper)-NCI-EORTC AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper), which is happening virtually on October 7-10, 2021.

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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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The proprietary technology, developed at Crown Bioscience’s recently acquired site in Leiden, The Netherlands (formerly known as OcellO B.V.), aims to improve clinical success rates by using the most patient-relevant tumor samples to better predict tumor response to potential drug candidates.

"Our goal is to leverage our core technologies to build a translational model system that adequately captures the tumor architecture and microenvironment, and improves the predictability of patient responses to treatment protocols for existing and potential therapeutic candidates," said Leo Price, PhD, Senior Vice President, In Vitro. "We believe this approach provides greater translational relevance in drug development by using immuno-competent primary human tumor tissue to help analyze drug candidate responses before the program enters clinical trial. This approach is an optimal fit with our mission to help deliver the right drug to the right patient at the right time."

The ‘3D Ex Vivo Patient Tissue Platform’ utilizes patient tumor tissue isolated from biopsies, surgical resections, ascites, or pleural effusion samples that are processed within 24 hours to preserve the tumor microenvironment. The automated high throughput platform uses high content 3D imaging and image analysis to quantify distinct responses of individual cell populations in fresh patient tissues. These analyses can assess responses to different doses of therapeutic candidates at various timepoints and can determine the effects of the drug or combination of drugs on tumor killing and immune cell proliferation.

"We believe this new service can help fill a critical gap in today’s research landscape with early translational patient-relevant ex vivo models that can assess efficacy and determine mechanisms of action," commented Armin Spura, PhD, Chief Executive Officer of Crown Bioscience. "This new service offering is designed to help mitigate the high failure rates of clinical programs in oncology, and was one of the objectives coming out of our recent OcellO acquisition. We are delighted to provide immediate value to our customers from this investment and look forward to the future value that this acquisition will bring."

AACR-NCI-EORTC AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper)
Researchers from CrownBio are conducting a poster presentation titled, "Novel Near Vivo Drug Response Platform for Oncology using 3D Ex Vivo Patient-Derived Microtumors" at the annual conference. The poster summarizes:

This 3D high content assay on ex vivo patient tumor material preserves native tumor microenvironement and architecture

Ex vivo testing using ultra fresh patient tumor samples maintains intact endogenous immune cell populations

Ongoing clinical trial collaborations with tissue providers for ovarian cancer, bladder cancer, NSCLC, and other tumor samples