On November 14, 2022 Quest Diagnostics (NYSE: DGX), the world’s leading provider of diagnostic information services, reported that its Board of Directors declared a quarterly cash dividend of $0.66 per share, payable on February 1, 2023 to shareholders of record of Quest Diagnostics common stock on January 18, 2023 (Press release, Quest Diagnostics, NOV 14, 2022, View Source [SID1234624020]).

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On November 14, 2022 Prelude Therapeutics Incorporated (Prelude) (Nasdaq: PRLD), a clinical-stage precision oncology company, reported financial results for the third quarter ended September 30, 2022 and provided an update on recent clinical and development pipeline progress (Press release, Prelude Therapeutics, NOV 14, 2022, View Source [SID1234624019]).

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"We made meaningful advancements in the third quarter and to date in the fourth quarter, including FDA clearance for two new INDs, one for PRT3645, a next generation, brain penetrant CDK4/6 inhibitor and one for PRT3789, a novel, first-in-class selective SMARCA2 degrader. We’ve also made good progress in the clinical development of our CDK9 inhibitor, PRT2527 and PRT1419, the MCL1 inhibitor," stated Kris Vaddi, Ph.D., Chief Executive Officer of Prelude.

"We continue to expand our highly innovative clinical pipeline. In order to focus resources on bringing compounds with the highest likelihood of success forward, we have decided to discontinue the internal development of our PRMT5 program. While PRT811 demonstrated a best-in-class safety profile and evidence of clinical activity in biomarker-selected patients with glioma and splicing mutated uveal melanoma, our prioritization reflects the high benchmark we set for clinical and regulatory success," Dr. Vaddi added. "We are committed to delivering impactful medicines to patients and building significant and sustainable value."

"Since joining Prelude, I have had the opportunity to critically review and to assess each program and identify clear next steps for clinical development," said Jane Huang, M.D., President and Chief Medical Officer of Prelude. "With this prioritization, we believe we can generate proof-of-concept clinical data in the next 12 to 24 months to guide our future regulatory pathways to approval. Our CDK9 and MCL1 inhibitors are selective and potent, with potentially superior safety profiles. PRT3645 was specifically designed to be a brain penetrant CDK4/6 inhibitor and our SMARCA2 molecule is a unique, first-in-class degrader, targeting specific patient populations. I believe these programs offer the best chance to improve patient outcomes and I share our investigators’ excitement in our highly differentiated molecules."

Recent Highlights and Upcoming Objectives

CDK9 Inhibitor Program: Given the compelling clinical activity recently reported with CDK9 inhibitors, PRT2527, as a more selective compound, has the potential to be best-in-class, with a favorable toxicity profile, allowing for rapid development in combinations. The PRT2527 Phase 1 dose escalation study in solid tumors has enrolled 11 patients to date. Dose dependent increases in exposure and target engagement were observed as evidenced by MYC and MCL1 depletion to levels associated with tumor regression in preclinical models. No adverse events leading to dose reduction or discontinuation have been reported. The Company remains on track to select a recommended Phase 2 dose by year-end. Prelude will use these safety data to continue cohort expansion in solid tumors, as well as to inform and rapidly progress the hematology trial.
ASH 2022: oral preclinical presentation
Session Name: 605. Molecular Pharmacology and Drug Resistance: Lymphoid Neoplasms: Targeting BH3, BTK, and CDK: PRT2527, a Novel Highly Selective Cyclin-Dependent Kinase 9 (CDK9) Inhibitor, Has Potent Anti-Leukemic Activity in Preclinical Primary Models of Human B-ALL, T-ALL, and CLL
Session Date: Saturday, December 10, 2022
Session Time: 2:00 PM – 3:30 PM
Presentation Time: 3:15 PM
Room: Ernest N. Morial Convention Center, 388-390
Present solid tumor dose escalation data at a medical conference in 1H 2023
RP2D in hematological malignancies in 2H 2023
Present initial clinical results for hematological malignancies at a medical conference in 2H 2023
MCL1 Inhibitor Program: To date, 26 patients have been enrolled in the PRT1419 Phase 1 solid tumor dose escalation and confirmation cohorts, including 15 patients at the recommended expansion dose of 80 mg/m2. PRT1419 has demonstrated a differentiated profile with no cardiotoxicity observed in patients to date. Cardiovascular parameters including troponin levels and ejection fraction changes were evaluated, in addition to standard safety, pharmacokinetics and target engagement metrics. The clinical pharmacodynamic profile of PRT1419 demonstrates the desired level of target engagement, as measured by caspase activation in peripheral mononuclear cells and reduction of CD14+ monocytes to levels associated with tumor regressions in preclinical models of hematological cancers. Advancement in hematological cancers will include monotherapy expansions in CLL and NHL based on a strong rationale for MCL1 inhibition and the need for novel treatments in second line.
Solid tumor data is expected to be presented at a medical conference 1H 2023
RP2D expected in hematological malignancies in 2H 2023
Hematological malignancy data expected to be presented in 2H 2023
Brain Penetrant CDK4/6: Phase 1 clinical trial is being initiated for PRT3645 in biomarker enriched patients with select tumor types including sarcomas, mesothelioma, gliomas, head and neck cancers and non-small cell lung cancer, in addition to breast cancer with or without brain metastases.
Present initial clinical results at a medical conference in 2H 2023
RP2D in solid tumors in 2H 2024

SMARCA2/BRM Protein Degrader Program: Prelude received IND clearance in October for PRT3879. Prelude plans to dose the first patient in Q1 2023. SMARCA2 inhibition has the greatest potential in patients with SMARCA4 deficient cancers, including up to 10% of all non-small cell lung cancers.
Provide Clinical update 2H 2023
PRMT5 Programs: In the Phase 1 trials for PRT543 and PRT811, both molecules were generally well tolerated. In the PRT811 clinical trial, a total of 82 patients across multiple tumor types were enrolled in dose escalation and expansion, of whom 57 had glioma or uveal melanoma. Out of 38 glioma patients (16 IDH+ and 22 IDH-), two complete responses were observed in IDH+ glioma. These responses remain ongoing for 62 and 21 weeks, respectively. In addition, out of 19 uveal melanoma patients (8 SPLC+ and 11 SPLC-), one confirmed PR (duration of response of 42 weeks) and a second ongoing unconfirmed PR were observed, both in patients who were SPLC+. The most common adverse events of any grade, with an incidence of >20% were nausea (57.3%), vomiting (41.5%) fatigue (31.7%), constipation (25.6%), and thrombocytopenia (24.4%), and were predominantly grade 1-2. The most common adverse events (grade ≥3), occurring >5% were thrombocytopenia (9.76%), anemia (7.32%), and fatigue (7.32%). Full results from the two clinical trials will be shared in the first half of 2023.
Third Quarter 2022 Financial Results

Cash, Cash Equivalents and Marketable Securities: Cash, cash equivalents, and marketable securities as of September 30, 2022, were $224.0 million. Prelude anticipates that its existing cash, cash equivalents and marketable securities will be sufficient to fund Prelude’s operations into the fourth quarter of 2024.

Research and Development (R&D) Expenses: For the third quarter of 2022, R&D expenses increased to $22.9 million for the three months ended September 30, 2022, from $22.7 million for the three months ended September 30, 2021. Included in research and development expenses for the quarter ending September 30, 2022, was $3.2 million of non-cash expense related to stock-based compensation expense, including employee stock options, compared to $3.3 million for the three months ended September 30, 2021. Research and development expenses remain steady as our clinical pipeline advances into clinical trials. We expect our research and development expenses to vary from quarter to quarter, primarily due to the timing of our clinical development activities.

General and Administrative (G&A) Expenses: For the third quarter of 2022, G&A expenses decreased to $7.5 million for the three months ended September 30, 2022, from $8.1 million for the three months ended September 30, 2021. Included in the general and administrative expenses for the quarter ended September 30, 2022, was $3.2 million of non-cash expense related to stock-based compensation expense, including employee stock options, as compared to $3.8 million for the same period in 2021. The decrease in general and administrative expenses was primarily due to non-cash stock-based compensation expense and prudent management of expenses.

Net Loss: For the three months ended September 30, 2022, net loss was $30.0 million, or $0.63 per share of common stock, basic and diluted compared to $30.7 million, or $0.66 per share, respectively, for the prior year period. Included in the net loss for the quarter ended September 30, 2022, was $6.4 million of non-cash expense related to the impact of expensing share-based payments, including employee stock options, as compared to $7.1 million for the prior year period.

On November 14, 2022 Pacira BioSciences, Inc. (Nasdaq: PCRX), the industry leader in its commitment to non-opioid pain management and regenerative health solutions, reported preliminary unaudited net product sales of $54.9 million for the month of October 2022 (Press release, Pacira Pharmaceuticals, NOV 14, 2022, View Source [SID1234624018]). The company’s net product sales include EXPAREL (bupivacaine liposome injectable suspension), ZILRETTA (triamcinolone acetonide extended-release injectable suspension), and the iovera° system. The company began recognizing sales of ZILRETTA in November 2021 after completing its acquisition of Flexion Therapeutics, Inc.

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"We continue to execute from a position of financial strength having recently reported adjusted EBITDA of $55 million in the third quarter of 2022 as EXPAREL continues to drive significant and durable operating cash flows. We remain well positioned for near- and long-term value creation as we grow revenue through increased market penetration, expansion into new indications, and enhanced reimbursement while simultaneously advancing new product development opportunities," said Dave Stack, chairman and chief executive officer of Pacira BioSciences.

"Even with continued near-term volatility in the marketplace, we remain confident in steady double-digit growth potential for EXPAREL and our entire portfolio of non-opioid pain management solutions as we expect our newly announced partnerships, such as our agreement with Sevāredent for oral and maxillofacial procedures, to take hold and begin to deliver on the promise of these collaborations. Moving forward, we remain steadfast in executing our strategy and look forward to 2022 being another record year for Pacira," continued Mr. Stack.

October 2022 Preliminary Net Product Sales Highlights

•EXPAREL net product sales were $45.0 million, compared with $42.5 million for October 2021. The company also reports average daily growth rates for EXPAREL to account for differences in the number of selling days per reporting period. EXPAREL average daily sales for the month of October 2022 were 106 percent of October 2021. There were 21 EXPAREL selling days in October 2022 and October 2021.
•ZILRETTA net product sales were $8.6 million for October 2022. ZILRETTA sales in October 2021 occurred prior to the completion of the company’s acquisition of Flexion in November 2021.
•iovera° net product sales were $1.3 million for October 2022, compared with $1.2 million for October 2021.

Since early 2020, the company’s revenues have been impacted by COVID-19 and pandemic-related challenges that included the significant postponement or suspension in the scheduling of elective surgical procedures due to public health guidance and government directives. While the degree of impact has diminished during the course of the pandemic due to the introduction of vaccines and the lessening of elective surgery restrictions, certain pandemic-related operational challenges persist. It remains unclear how long it will take the elective surgery market to normalize or if restrictions on elective procedures will recur due to future COVID-19 variants or otherwise.

The company is not providing 2022 revenue or gross margin guidance at this time given the continued uncertainty around labor shortages, COVID-19, and the pace of recovery for the elective surgery market. To provide greater transparency, the company is reporting monthly intra-quarter unaudited net product sales for EXPAREL, ZILRETTA, and iovera° until it has gained enough visibility around the impacts of COVID-19. The company is also providing weekly EXPAREL utilization and elective surgery data within its investor presentation, which is accessible at investor.pacira.com. Pacira completed its acquisition of Flexion Therapeutics on November 19, 2021, which added ZILRETTA to its commercial offering.

The preliminary net product sales included in this press release are preliminary, unaudited and subject to change as certain required adjustments for product discount and rebate programs are finalized after the end of the quarter. This financial information does not present all information necessary for an understanding of the company’s fourth quarter and full-year 2022 financial results. Pacira expects to report its complete financial results for the fourth quarter and full-year 2022 in the first quarter of 2023.

On November 14, 2022 Orionis Biosciences, a life sciences company pioneering innovation of highly selective and tunable therapeutics for cancer and beyond, reported that preclinical data supporting its A-Kine platform for rational design of cis-acting immuno-cytokines at the 14th Annual PEGS Europe Protein & Antibody Engineering Summit, taking place November 14 – 16 in Barcelona, Spain (Press release, Orionis Biosciences, NOV 14, 2022, View Source [SID1234624017]). The data demonstrate potent anti-tumor activity across multiple classes of targeted cytokines.

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Cytokines are powerful regulators of the immune system and attractive therapeutic effector candidates. However, their sites of action must be restricted to avoid systemic toxicity. To achieve spatial control of cytokine bioactivity, Orionis has developed a proprietary biologics platform that integrates a strategic "plug-and-play" assembly of modular biomolecular building blocks into therapeutic agents with unique conditional effector functions and cell-target selectivity. These conditionally active, cis-acting cytokines aim to trigger anti-tumor immune responses even in cold tumors that lack prevalent immune involvement and are refractory to checkpoint inhibitor and other therapies.

"Today we shared preclinical data that represent exciting progress for our proprietary A-Kine platform. Our R&D engine, inspired by nature’s intrinsic mechanisms for disease control, has the potential to address some of the biggest challenges in oncology drug discovery and beyond," said Nikolai Kley, Ph.D., Founder, President and Chief Executive Officer of Orionis Biosciences. "As we look ahead, we anticipate IND submission and the start of a conditionally active cytokine Phase 1 trial in 2023."

Orionis’ deep and diversified A-Kine pipeline comprises multiple cytokine classes, including re-engineered interferons (IFNs), interleukins (ILs) and tumor necrosis factors (TNFs). In conjunction with an arsenal of cell-targeting strategies, Orionis is harnessing the therapeutic potential of these cytokines to reprogram immune cells and reactivate the cancer immunity cycle, and thereby the immune system’s natural mechanisms of disease control.

The company presented its advances and breakthroughs in design, engineering and development of exquisitely target-selective A-Kines incorporating:

Cis-acting Interferons to promote immune system recognition and infiltration of tumors
Cis-acting Interleukin-2 to directly activate CD8+ tumor cytotoxic T cells
These unique agents exhibit potent, single agent anti-tumor activity in multiple preclinical cancer models, mediated by targeting of key immune cells, including subtypes of myeloid cells and tumor cytotoxic CD8+ T cells, and PD-1/PD-L1 checkpoint mechanisms. Orionis’ A-Kine pipeline reflects multiple protein engineering innovations and contains an array of programs in lead optimization and IND-enabling phases.

Details of today’s presentation are as follows:

14th Annual PEGS Europe Protein & Antibody Engineering Summit, November 14–16, 2022, Barcelona, Spain

Title: A-Kine Platform: On-Target Cytokines to Reprogram Cell Targets for Immuno-Oncology
Date and Time: Monday, November 14, 11:45 a.m. CET
Presenter: Erik Depla, Ph.D., Director of Biology, Orionis Bio
Orionis recently announced a $55 million financing to support entry of its lead A-Kine cancer immunotherapy programs into the clinic. The company anticipates IND submission and start of a Phase 1 study of a conditionally active cytokine in 2023. In addition to the A-Kine platform, Orionis has developed the Allo-Glue protein degradation platform for discovery and rational design of small molecule molecular glues. These types of conditionally active small molecules are designed to tackle traditionally undruggable or elusive drug targets by harnessing nature’s cellular machinery to degrade and dispose of proteins that cause and/or promote disease.

On November 14, 2022 Onconova Therapeutics, Inc. (NASDAQ: ONTX), ("Onconova"), a clinical-stage biopharmaceutical company focused on discovering and developing novel products for patients with cancer, reported plans for a Phase 1/2a trial of narazaciclib combined with letrozole in recurrent metastatic low-grade endometrioid endometrial cancer (LGEEC) (Press release, Onconova, NOV 14, 2022, View Source [SID1234624016]). In addition, the Company reported its third quarter 2022 financial results and provided a business update.

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"Onconova’s upcoming Phase 1/2a trial has been thoughtfully designed to explore narazaciclib’s potential as a best-in-class therapy when combined with letrozole in recurrent low grade endometrioid endometrial cancer (LGEEC)," said Bhavana Pothuri, MD, Professor, Department of Obstetrics and Gynecology at NYU Grossman School of Medicine and Director, Gynecologic Oncology Research; Perlmutter Cancer Center and principal investigator of the trial. "Data from prior randomized and single-arm trials in LGEEC have validated the anti-cancer activity of letrozole combined with agents that, like narazaciclib, potently inhibit CDK 4/6. However, currently available CDK 4/6 inhibitors are hampered by limitations related to safety, tolerability, and treatment resistance. Moreover, none are currently FDA approved for endometrial cancer creating an urgent need for improved treatment options for LGEEC patients. Clinical and preclinical data suggest narazaciclib’s differentiated inhibitory profile may allow it to address this unmet need, which is a hypothesis I look forward to evaluating with my colleagues in Onconova’s upcoming study."

Endometrioid Endometrial Cancer and the Upcoming Phase 1/2a Trial

Endometrial cancer (EC) arises in the uterine lining and is the most common cancer of the female reproductive organs. Endometrioid endometrial cancer is the most common subtype of EC, accounting for approximately 75% of cases. Onconova expects to initiate a multi-center Phase 1/2a trial evaluating its multi-kinase inhibitor narazaciclib in combination with letrozole as a second- or third-line therapy for the treatment of recurrent metastatic LGEEC in 1Q23. Both narazaciclib and letrozole will be administered orally with a continuous daily dosing schedule in the trial, which will begin with a Phase 1 dose escalation phase before moving to a Phase 2 expansion cohort designed to enroll approximately 30 patients.

The primary objective of the Phase 1 portion of the trial will be to evaluate safety, tolerability, pharmacokinetics and pharmacodynamics in order to determine a recommended Phase 2 dose (RP2D) of the combination. The primary objective of the Phase 2 portion will be to evaluate the efficacy of the combination at the RP2D, as measured by progression-free survival at 24 weeks. The estrogen/progesterone receptor status of participants will be recorded as part of an exploratory objective. The trial will be conducted at 6 to 10 sites in the United States. Initiation of the trial is expected in 1Q23. Preliminary data are expected in 4Q23.

Third Quarter 2022 and Recent Highlights:

·Safety data from the ongoing Phase 1 solid tumor trials of narazaciclib in the United States and China continue to be encouraging with the maximum tolerated dose not yet reached in either study. Both trials are currently enrolling patients into their fifth dose escalation cohort. The trial in the United States is evaluating a continuous daily dosing regimen, while participants in the trial in China receive once daily doses of narazaciclib only on days 1-21 of 28-day cycles. A protocol amendment to enable further dose escalation in the trial in China is being prepared.

·The investigator-sponsored Phase 1/2a trial evaluating rigosertib in combination with the checkpoint inhibitor nivolumab in KRAS-mutated non-small cell lung cancer (NSCLC) continues to enroll patients in its dose-expansion cohort. Updated data presented at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Annual Congress showed an encouraging signal of efficacy in the trial’s extensively pre-treated population, with one complete response, two partial responses, and one instance of stable disease achieved in fourteen evaluable patients. Responses were achieved in patients with three distinct KRAS mutations, corroborating preclinical data suggesting the MOA of rigosertib is mutation agnostic. The studied doublet has been well tolerated in the trial. Additional data from the trial are expected in 1H23.

·Rigosertib’s additional investigator-sponsored trials also continue to progress. A Phase 2 trial of rigosertib in combination with pembrolizumab in patients with checkpoint inhibitor refractory metastatic melanoma is on track for initiation. The Phase 2 trial of rigosertib monotherapy in advanced squamous cell carcinoma associated with recessive dystrophic epidermolysis bullosa continues to enroll patients and was recently the subject of a non-dilutive grant.

Steven M. Fruchtman, M.D., President and Chief Executive Officer of Onconova, commented, "We look forward to initiating the Ph 1/ 2a trial of the narazaciclib doublet in LGEEC. CDK 4/6 inhibitors are not health authority approved in this space that has a great unmet medical need for novel approaches. The advancement of rigosertib’s investigator-sponsored studies have complemented efforts in our lead narazaciclib program. Recently reported data from a Phase 1/2a trial showed rigosertib when combined with a PD-1 checkpoint inhibitor to drive complete and partial responses in advanced KRAS-mutated non-small cell lung cancer. These responses were achieved in patients with three distinct KRAS mutations who had failed prior checkpoint inhibitor therapy, thereby confirming rigosertib’s KRAS mutation-agnostic mechanism of action and potential to synergize with anti-PD-1 agents. We will be reporting additional data from this trial as patient accrual continues, which will be key to informing our next steps in this program."

Third Quarter Financials

Cash and cash equivalents as of September 30, 2022 were $42.6 million compared with $55.1 million as of December 31, 2021. The Company believes that its cash and cash equivalents will be sufficient to fund ongoing clinical trials and business operations into 2024.

Research and development expenses were $3.6 million for the third quarter of 2022, compared with $1.8 million for the third quarter of 2021.

General and administrative expenses were $2.1 million for the third quarter of 2022, compared with $2.3 million for the third quarter of 2021.

Net loss for the third quarter of 2022 was $5.4 million, or $0.26 per share on 20.9 million weighted shared outstanding, compared with a net loss of $3.5 million, or $0.22 per share for the third quarter of 2021 on 16.0 million weighted shared outstanding.

Conference Call and Webcast

Onconova will host an investment community conference call beginning at 4:30 p.m. Eastern Time, during which management will discuss financial results for the third quarter of 2022, provide a business update, and answer questions. Interested parties can participate by dialing (800) 715-9871 (domestic callers) or (646) 307-1963 (international callers) and using conference ID 6078502.

A live webcast of the conference call will be available in the Investors & Media section of the Company’s website at www.onconova.com. A replay of the webcast will be available on the Onconova website for 90 days following the call.