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.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

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

                  Schedule Your 30 min Free Demo!

"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.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

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

                  Schedule Your 30 min Free Demo!

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.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

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

                  Schedule Your 30 min Free Demo!

"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.

On November 14, 2022 OncoNano Medicine, Inc. reported the presentations of positive preclinical data on the company’s ON-BOARD pH-activatable delivery platform at the 37th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) in Boston, Massachusetts (Press release, OncoNano Medicine, NOV 14, 2022, View Source [SID1234624015]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

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

                  Schedule Your 30 min Free Demo!

The data presented at SITC (Free SITC Whitepaper) 2022 demonstrated the capability of the ON-BOARD platform for effective encapsulation and improvement of the therapeutic index of a variety of therapeutic payloads, including bispecific T cell engagers (TCE) and a therapeutic cytokine – IL-2-Fc, using relevant animal models.

The ON-BOARD platform is designed to protect oncology intervention payloads systemically and release them in the acidic tumor microenvironment, minimizing systemic exposure and toxicity. OncoNano’s lead clinical candidate, pegsitacianine, currently in Phase 2 clinical trials, is formulated with ON-BOARD, and the clinical data has validated its pH-activated tumor specificity.

In the two separate presentations, a variety of TCEs including solitomab, runimotamab and several TCEs with undisclosed targets as well as a human IL-2 fused with IgG Fc were encapsulated using the ON- BOARD platform. The data demonstrated that:

ON-BOARD successfully encapsulated TCEs across a range of different targets and structural configurations without any protein engineering involved
ON-BOARD-encapsulated TCEs demonstrated rapid release and high pH specificity as well as pH- activated cytotoxicity against various cancer cell lines in vitro
ON-BOARD encapsulation of an undisclosed TCE significantly improved its tolerability in vivo compared to the unencapsulated molecule and inhibited the growth of a poorly immunogenic "cold" tumor model with in-tumor payload activation confirmed by PD markers
ON-BOARD-encapsulated IL-2-Fc showed robust anti-tumor efficacy in both the "hot" MC38 and the "cold" B16F10 tumors and greatly suppressed systemic toxicity compared to unencapsulated IL-2-Fc
"We were excited to share the positive data on the encapsulation of a variety of bispecific T cell engagers and a therapeutic cytokine and the significant improvement of therapeutic index without complicated protein engineering," said Tian Zhao, PhD, Vice President of Research and Development at OncoNano. "We look forward to developing this technology for clinical translation with these types of payload molecules in the near future."

On November 14, 2022 Achieve Life Sciences, Inc. (NASDAQ: ACHV), a late-stage clinical pharmaceutical company committed to the global development and commercialization of cytisinicline for smoking cessation and nicotine dependence, reported third quarter 2022 financial results and provided an update on the cytisinicline development program (Press release, OncoGenex Pharmaceuticals, NOV 14, 2022, View Source [SID1234624013]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

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

                  Schedule Your 30 min Free Demo!

Highlights

Completion of targeted enrollment in Phase 3 ORCA-3 clinical trial of cytisinicline in 750 adult smokers was announced in September

Early completion of targeted enrollment in the Phase 2 ORCA-V1 clinical trial of cytisinicline in 150 adult nicotine e-cigarette users was announced in November

New active pharmaceutical ingredient (API) suite construction completed by Sopharma, expanding the global commercial manufacturing capacity for cytisinicline

"Completing enrollment in the ORCA-3 trial this quarter and more recently, the ORCA-V1 trial, has moved us closer to potentially bringing a critical treatment option to people who wish to end their nicotine dependence," stated John Bencich, CEO of Achieve Life Sciences. "We are excited to build upon the previously reported cessation benefit, safety, and tolerability of cytisinicline and look forward to releasing top-line data for both trials in the second quarter of next year."

Completed Enrollment in Confirmatory Phase 3 ORCA-3 Trial

In September, Achieve announced the completion of targeted enrollment of 750 adult smokers in its confirmatory Phase 3 ORCA-3 clinical trial of cytisinicline being conducted across 20 clinical trial locations in the United States. The participants in ORCA-3 were randomized to one-of-three study arms to determine the efficacy and safety of cytisinicline administered for either 6 or 12 weeks, compared to placebo. Similar to the previously reported ORCA-2 trial, the primary endpoint is biochemically verified continuous abstinence during the last four weeks of treatment in the 6 and 12-week cytisinicline treatment arms compared to placebo. Each treatment arm will be compared independently to the placebo arm and the trial will be determined to be successful if either or both of the cytisinicline treatment arms show a statistical benefit compared to placebo. Topline ORCA-3 data are currently expected to be reported in Q2 of 2023.

Early Completion of Enrollment in Phase 2 ORCA-V1 Trial

In November, Achieve announced the early completion of targeted enrollment of 150 adult users of nicotine e-cigarettes in the Phase 2 ORCA-V1 clinical trial of cytisinicline being conducted across 5 clinical trial locations in the United States. Participants were randomized in this two-arm trial to receive either cytisinicline, dosed at 3 mg three times daily, or placebo, for a period of 12 weeks. All subjects are also receiving standardized behavioral support throughout the trial. The primary outcome assessment of ORCA-V1 will be continuous vaping abstinence during the final 4 weeks of treatment. ORCA-V1 is supported through grant funding from the National Institute on Drug Abuse (NIDA) of the National Institutes of Health (NIH). Topline results are expected to be reported in Q2 of 2023.

Sopharma Expansion of Manufacturing Facility

Achieve’s commercial manufacturing partner, Sopharma, financed and completed the build out of a new dedicated cytisinicline API purification suite at its primary manufacturing plant. At an estimated build out cost of more than €3 million, the newly completed API suite significantly expands the capacity to produce quantities of cytisinicline at a global scale. The new API suite complements Sopharma’s capacity to produce nearly 3 billion tablets annually.

Financial Results

As of September 30, 2022, the company’s cash, cash equivalents, and restricted cash were $18.2 million. Total operating expenses for the three and nine months ended September 30, 2022 were $12.6 million and $29.9 million, respectively. Total net loss for the three and nine months ended September 30, 2022 was $13.1 million and $31.1 million, respectively.

As of November 10, 2022, Achieve had 9,710,747 shares of common stock outstanding.

Conference Call Details

Achieve will host a conference call today at 4:30 PM EST, Monday, November 14, 2022. To access the webcast, please use the following link 3Q22 Earnings Webcast. Alternatively, you may access the live conference call by dialing (877) 269-7756 (Domestic) or (201) 689-7817 (International) and referencing conference ID 13733008. A webcast replay will be available approximately three hours after the call and will be archived on the website for 90 days.