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ESSA Pharma Provides Corporate Update and Reports Financial Results for Fiscal Fourth Quarter and Year Ended September 30, 2023

On December 12, 2023 ESSA Pharma Inc. ("ESSA", or the "Company") (NASDAQ: EPIX), a clinical-stage pharmaceutical company, focused on developing novel therapies for the treatment of prostate cancer, reported a corporate update and announced financial results for the fourth quarter and fiscal year ended September 30, 2023 (Press release, ESSA, DEC 12, 2023, View Source [SID1234638508]).

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"We are pleased with the progress made in 2023 with masofaniten (EPI-7386), our first-in-class N-terminal domain androgen receptor inhibitor for the treatment of prostate cancer, which culminated recently in the presentation of Phase 1 dose escalation data at two medical meetings where we showed that the combination of masofaniten with enzalutamide was well-tolerated and demonstrated deep and durable reductions in prostate-specific antigen ("PSA") in patients with metastatic castration-resistant prostate cancer ("mCRPC")," said David Parkinson, MD, President and CEO of ESSA. "Looking ahead, we will be focused on executing the Phase 2 combination study of masofaniten and enzalutamide in mCRPC patients as well as investigating masofaniten in combination with other standard of care antiandrogens to further elucidate its potential as a new treatment for prostate cancer patients at earlier stages of the disease. We are entering 2024 with a strong cash balance and a runway that is expected to fund our planned operations through 2025."

Fourth Quarter Fiscal 2023 and Recent Highlights

Masofaniten Combination Studies

Reported updated Phase 1 dose escalation data from the four cohorts of its ongoing Phase 1/2 study evaluating masofaniten in combination with enzalutamide in patients with mCRPC naïve to second-generation antiandrogens but may have been treated with chemotherapy in the metastatic castration-sensitive setting. The results demonstrated that the combination continues to be well-tolerated with deep and durable reductions in PSA. Across all dose cohorts (n=16) including patients in the recently enrolled Cohort 4, 88% of patients achieved PSA50, 81% of patients achieved PSA90, 69% of patients achieved PSA90 in less than 90 days, and 56% of patients achieved PSA <0.2ng/mL. These data were presented at the 2023 Prostate Cancer Foundation Scientific Retreat and at the European Society for Medical Oncology 2023 Congress.
Initiated the Phase 2 portion of its Phase 1/2 study evaluating the combination of masofaniten and enzalutamide compared to enzalutamide monotherapy in patients with mCRPC naïve to second-generation antiandrogens but may have been treated with chemotherapy in the metastatic castration-sensitive setting. The Phase 2 portion of the study is an open-label randomized study comparing 160 mg once-daily of single agent enzalutamide to the combination of masofaniten with enzalutamide, and is expected to enroll approximately 120 patients. The recommended Phase 2 combination dose was identified as masofaniten 600 mg twice-daily combined with enzalutamide 160 mg once daily. ESSA plans to provide guidance for timing of the public disclosure of initial data once the Phase 2 portion has been underway for several months.
Initiated two additional masofaniten combination arms as part of the ongoing Phase 1 masofaniten study. One arm will evaluate masofaniten in combination with abiraterone acetate and prednisone in patients with either metastatic castration-sensitive prostate cancer ("mCSPC") or mCRPC while the second arm will evaluate masofaniten in combination with apalutamide in patients with non-metastatic CRPC after 12 weeks of masofaniten single agent.
An investigator-sponsored neoadjuvant study was also initiated evaluating neoadjuvant use of the combination of masofaniten and darolutamide compared to darolutamide monotherapy in high-risk patients undergoing prostatectomy.
Masofaniten Monotherapy Study

On track to complete the Phase 1b masofaniten monotherapy study evaluating masofaniten in patients with late-line mCRPC. The initial results from the study were reported at the 2023 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Genitourinary Cancers Symposium and demonstrated that masofaniten monotherapy was well-tolerated, achieved clinically significant exposures, and showed preliminary signals of anti-tumor activity in a subset of patients. ESSA plans to present the complete Phase 1a and 1b monotherapy results in 2024 at a medical conference.
Summary Financial Results
(Amounts expressed in U.S. dollars)

Net Loss. ESSA recorded a net loss of $26.6 million for the year ended September 30, 2023 compared to a net loss of $35.1 million for the year ended September 30, 2022. For the year ended September 30, 2023, this included non-cash share-based payments of $5.0 million compared to $7.9 million for the prior year, recognized for stock options granted and vesting. Net loss for the fourth quarter ended September 30, 2023 was $5.5 million compared to a net loss of $6.3 million for the fourth quarter ended September 30, 2022. The decrease in the fourth quarter was primarily attributed to a decrease in general and administration expenditures and an increase in interest and other income.
Research and Development ("R&D") expenditures. R&D expenditures for the year ended September 30, 2023 were $21.3 million compared to $24.4 million for the year ended September 30, 2022, and include non-cash costs related to share-based payments ($2.6 million for the year ended 2023 compared to $4.3 million for the year ended 2022). The decrease in R&D expenditures for the year ended September 30, 2023 was primarily attributed to decreases in preclinical and data analysis, share-based payments and manufacturing costs. R&D expenditures for the fourth quarter ended September 30, 2023 were $5.2 million compared to $4.4 million for the fourth quarter ended September 30, 2022. The primary drivers for the increase were due to increased clinical costs as the Company advances masofaniten through its clinical trials.
General and administration ("G&A") expenditures. G&A expenditures for the year ended September 30, 2023 were $10.8 million compared to $12.5 million for the year ended September 30, 2022, and include non-cash costs related to share-based payments of $2.4 million for the year ended 2023 compared to $3.6 million for the year ended 2022. G&A expenditures for the fourth quarter ended September 30, 2023 were $1.9 million compared to $2.8 million for the fourth quarter ended September 30, 2022. The decrease for the fourth quarter was primarily due to decreased share-based payments and lower insurance renewal premiums.
Liquidity and Outstanding Share Capital

At September 30, 2023, the Company had available cash reserves and short-term investments of $148.1 million. The Company’s cash position is expected to be sufficient to fund current and planned operations through 2025.
On November 6, 2023, the Company announced that it had entered into an Open Market Sale AgreementSM (the "ATM Sales Agreement") with Jefferies LLC, effective as of November 3, 2023. Under the ATM Sales Agreement, ESSA may, within the period that the ATM Sales Agreement is in effect, sell its common shares from time to time for up to $50.0 million in aggregate sales proceeds. No offers or sales of common shares will be made in Canada, to anyone known by Jefferies LLC to be a resident of Canada or on or through the facilities of any stock exchange or trading markets in Canada.
As of September 30, 2023, the Company had 44,100,838 common shares issued and outstanding.
In addition, as of September 30, 2023, there were 2,927,477 common shares issuable upon the exercise of warrants and broker warrants. This includes 2,920,000 prefunded warrants at an exercise price of $0.0001, and 7,477 warrants at a weighted average exercise price of $42.80. There were 8,112,774 common shares issuable upon the exercise of outstanding stock options at a weighted-average exercise price of $4.97 per common share.

Shinobi Therapeutics Launches with Completion of $51M Series A to Advance Hypoimmune iPS-T Cell Therapy Platform

On December 12, 2023 Shinobi Therapeutics (Shinobi), the biotechnology company developing a new class of immune evasive iPS-T cell therapies, reported that it has closed a $51 million Series A financing (Press release, Shinobi Therapeutics, DEC 12, 2023, View Source [SID1234638509]). The oversubscribed round was led by EQT Life Sciences, F-Prime Capital and Eight Roads Ventures Japan, with participation from Astellas Venture Management, Fast Track Initiative (FTI), JIC Venture Growth Investments, and D3 LLC. Shinobi will use the funds to advance its ‘Katana’ iPS-T cell therapy platform and progress its first program to treat GPC3+ solid tumor cancers toward the clinic.

"We’re thrilled to launch Shinobi out of stealth with a clear mission to develop an all-in-one solution to address some of the biggest challenges facing the cell therapy space today," said Dan Kemp, Ph.D., Chief Executive Officer of Shinobi. "Having led several cell therapy programs at other global companies, I’ve never encountered a technology platform that is capable of advancing the field as dramatically as this."

Cell therapies have shown remarkable promise in treating blood cancers and other intractable diseases, but manufacturing costs render these therapies inaccessible to many patients around the world. Off-the-shelf cell therapies offer a more scalable manufacturing approach, but face the additional challenge of allo-rejection, as patients’ immune systems reject donor-derived and engineered cells as foreign invaders. To overcome this immune response, patients today receive immunosuppressive drugs before treatment, which can often result in unwanted side effects and serious complications. Shinobi is taking a different approach by creating therapies that work with, not against, the patient’s immune system.

Shinobi’s unique approach uses methods developed by scientific co-founders Tobias Deuse, M.D. and Shin Kaneko, M.D., Ph.D., to first edit iPSCs to become highly immune evasive before they are differentiated with the company’s proprietary Katana technology to create CD8αβ iPS-T cells. "Shinobi’s Katana platform has the potential to make CAR-T cell therapies accessible to patients on a global scale," said Carl June, M.D., who has been appointed to Shinobi’s Scientific Advisory Board.

"Shinobi stands alone in the growing cell therapy field by engineering the most comprehensive immune evasion technology directly into its cell products," said Robert Weisskoff, Ph.D, Partner at F-Prime Capital. "With our colleagues at Eight Roads Ventures Japan and Donald Payan M.D., we envisioned combining the decade’s worth of iPSC research pioneered by Shin Kaneko M.D., Ph.D and developed by Yasumichi Hitoshi M.D., Ph.D. and Ryosuke Gonotsubo in Kyoto, Japan, with breakthrough immune evasion technology created by Tobias Deuse, M.D. in San Francisco. Shinobi Therapeutics is the result of these merged technologies, which delivers an allogeneic platform that effectively protects cell therapies from T cells, innate immune cells, as well as antibody-mediated immune rejection."

"The full potential of allogeneic cell therapies will likely never be realized without overcoming the challenge of allo-rejection," said Fouad Azzam, Ph.D., Partner at EQT Life Sciences. "Shinobi’s hypoimmune technology opens the door to a broader pipeline of off-the-shelf cell therapies far beyond T cells and oncology. We’re planning to leverage this platform in important areas of regenerative medicine and autoimmune disease."

ChemDiv Presented Non-Clinical Summary Data for The Best-in-Class Selective FLT3 Clinical Candidate at the 65th ASH Annual Meeting and Exposition with Its Partners and Sponsors

On December 12, 2023 ChemDiv Inc., dedicated to partnering in discovery and development of breakthrough therapies based on its unique chem-bio platforms, reported the presentation of non-clinical summary data for the best-in-class selective FLT3 clinical candidate at the 65th ASH (Free ASH Whitepaper) Annual Meeting and Exposition in San Diego, CA (Press release, ChemDiv, DEC 12, 2023, View Source [SID1234638507]). "Therapeutic Targeting of FLT3 gatekeeper mutation with E2082-0047 in traditional and a novel Immunocompetent murine adoptive transfer model of AML" was presented by collaborators from University of Cincinnati, Ohio, Molsoft LLC and Expert Systems Inc of San Diego, California, and Eilean Therapeutics LLC from Dover, Delaware. The presentation highlighted best-in-class potency and selectivity against gatekeeper resistant FLT-mutant AML and compelling survival benefit superior to gilteritinib in a fully immunocompetent Nmp1CAFLT3ITD-F692L AML adoptive transfer model, supporting the clinical candidate’s ongoing clinical development.

In collaboration with rational design groups of Molsoft and Expert Systems, John Byrd’s lab at University of Cincinnati, ChemDiv deployed a muti-targeting/multi-property optimization approach to achieve a 400-1000x selectivity of the resulting clinical candidate, which translated in best-in-class efficacy, safety, tolerability and developable pharmacology advantages delivered to partners at Eilean Therapeutics LLC.

Plus Therapeutics Partners With K2bio for Development of Novel Tests for Cerebrospinal Fluid (CSF) Tumor Cell and Molecular Biomarker Analyses

On December 12, 2023 Plus Therapeutics, Inc. (Nasdaq: PSTV) (the "Company"), a clinical-stage pharmaceutical company developing targeted radiotherapeutics with advanced platform technologies for central nervous system (CNS) cancers, reported that it has partnered with K2bio (Houston, Texas) to implement novel analysis for cerebrospinal fluid (CSF) tumor and molecular biomarkers for CNS cancers (Press release, Plus Therapeutics, DEC 12, 2023, View Source [SID1234638505]). Initial clinical specimen processing and testing will begin in Q1 2024 in the Company’s ongoing Phase 1 ReSPECT-LM trial of rhenium (186Re) obisbemeda in patients with leptomeningeal metastases (LM). This trial is currently receiving grant funding through The Cancer Prevention and Research Institute of Texas (CPRIT). The Company expects testing costs to be partially covered under this grant.

"The initial diagnosis, therapeutic selection and monitoring of patients with CNS cancers such as leptomeningeal metastases are significant problems in everyday clinical practice," said Marc H. Hedrick, M.D., President & Chief Executive Officer of Plus Therapeutics. "To turn these very lethal CNS cancers into treatable diseases, we must ideally address both the diagnostic as well as the therapeutic needs of caregivers and patients. This partnership with K2bio is the next part of our overall strategy to address both needs in parallel."

K2bio is a hybrid contract research organization (CRO) enabling life science companies to develop the next generation of innovative therapies. K2bio is based in Houston and is part of the Texas Medical Center life sciences ecosystem specializing in all aspects of translational cancer diagnostic and therapeutic research and development.

"K2bio is a leader in enabling rapid diagnostic and therapeutic progress for innovative companies such as Plus," said Colby Suire, PhD, acting President and CEO of K2bio. "We have all the necessary capabilities and expertise to accelerate and support Plus’ mission to be a leader in the development of targeted radiotherapeutics and related diagnostics for CNS cancers."

Plus’ tumor cell and molecular biomarker analysis is an exploratory endpoint in the ReSPECT-LM Phase 1 trial that has shown promise in early cohorts. In Phase 1/part A of the ReSPECT-LM trial presented at the 2023 SNO/ASCO Meeting in San Francisco, Plus data showed an average 53% reduction in CSF tumor cells 28 days after a single intrathecal administration of rhenium (186Re) obisbemeda in patients with LM.

The FDA has granted Fast Track designation to rhenium (186Re) obisbemeda for the treatment of LM, and the ReSPECT-LM Phase 1 program continues to be funded in part by a 3-year $17.6 million grant from the Cancer Prevention & Research Institute of Texas (CPRIT). Patients interested in learning more about the ReSPECT-LM trial can visit ClinicalTrials.gov (NCT05034497).

Onconova Therapeutics’ Narazaciclib ASH Poster Highlights Activity In Treatment Resistant Mantle Cell Lymphoma

On December 12, 2023 Onconova Therapeutics, Inc. (NASDAQ: ONTX), ("Onconova" or "the Company"), a clinical-stage biopharmaceutical company focused on discovering and developing novel products for patients with cancer, reported preclinical data, highlighting narazaciclib’s preclinical activity in Bruton’s kinase inhibitor (BTKi)-resistant mantle cell lymphoma (MCL), in a poster presented on December 11, 2023 at the 65th Annual Meeting of the American Society for Hematology (ASH 2023) in San Diego (Press release, Onconova, DEC 12, 2023, View Source [SID1234638504]).

"We are pleased to have shared data at ASH (Free ASH Whitepaper) 2023 from preclinical studies with narazaciclib in MCL models. These results, which are consistent with data presented this year at the international MCL conferences, demonstrate that treatment with narazaciclib led to significant tumor growth inhibition when used as a single agent and that combination with ibrutinib demonstrated synergy, in both ibrutinib-sensitive and -resistant in vitro and in vivo settings," said Steve Fruchtman, M.D., President and Chief Executive Officer. "These data are important because they provide further evidence for the potential use of narazaciclib in cancers with cyclin over-expression and elaborate our understanding of narazaciclib’s mechanism of action, including its ability to promote G1 cell cycle blockade."

Dr. Fruchtman continued, "We believe that these data, along with the preclinical data presented on Friday, December 8th at the San Antonio Breast Cancer Symposium (SABCS), further underscore the impressive and differentiated profile of narazaciclib. The data presented at SABCS highlight narazaciclib’s multi-kinase activity, its ability to target resistance pathways missed by other CDK4/6 inhibitors, and its differentiated anti-tumor and immunomodulatory activity. The data presented at ASH (Free ASH Whitepaper) 2023 show that narazaciclib, in combination with BTKi’s such as ibrutinib, also trigger metabolic reprogramming alongside DNA damage."

"The totality of these data is helping us to shape the clinical program for narazaciclib, including the lead indication of LGEEC, with further potential to expand into additional investigator-sponsored studies in breast, ovarian, and other cancers. We are pleased with the early Phase 1/2 data for narazaciclib monotherapy and in combination with letrozole, showing lower levels of neutropenia and diarrhea, and the potential for once daily dosing. Both of these attributes could position narazaciclib as a differentiated and improved CDK4/6i. Looking ahead, we are enthusiastic to advance the clinical program for narazaciclib in 2024 and to update our stakeholders regarding our progress, including the planned completion of dose escalation studies, definition of an RP2D, and development of our registrational trial plans for LGEEC. The data presented at ASH (Free ASH Whitepaper) suggest narazaciclib is a drug with the potential to target a variety of cancer indications with an unmet medical need, including MCL," concluded Dr. Fruchtman.

Poster Highlights

Title: Narazaciclib, a differentiated CDK4/6 antagonist, prolongs cell cycle arrest and metabolomic reprogramming, enabling restoration of ibrutinib sensitivity in BTKi-resistant mantle cell lymphoma

Objectives: To evaluate the activity and mechanism of action of narazaciclib as a single agent and in combination with ibrutinib, in comparison to the standard-of-care ibrutinib, in preclinical models of MCL that are sensitive and resistant to ibrutinib treatment.

Snapshot of the Results and Conclusions:

Tumor Growth Inhibition: Narazaciclib showed safety and efficacy as a single agent in preclinical MCL models, including ibrutinib-resistant settings, with significant reductions in cell viability.
Combination Synergy: The narazaciclib plus ibrutinib combination showed synergy in vitro and in vivo, especially in ibrutinib-resistant models, with overall greater synergy, measured by lower "Combination Index" values, versus ibrutinib-sensitive cells.
Cell Cycle Blockade: The combination of narazaciclib plus ibrutinib induces a superior G1 cell cycle blockade in both ibrutinib-sensitive and ibrutinib-resistant MCL cells.
Metabolic programming: In ibrutinib-resistant cases, the synergy between narazaciclib and ibrutinib triggers metabolic reprogramming alongside DNA damage, mediated by the USP24 and P53 axis, as evidenced by several assays to assess mitochondrial metabolism.
Together, these preclinical data suggest that narazaciclib has important single agent activity and the potential to restore ibrutinib sensitivity in BTKi-resistant models, successfully meeting the primary objective of the study.

A copy of the poster is available on the "Scientific Presentations" section of the Onconova website.