On December 17, 2024 ESSA Pharma Inc. ("ESSA," or the "Company") (NASDAQ: EPIX), a clinical-stage pharmaceutical company that, prior to the discontinuation of its clinical trials and preclinical and other development programs, has been focused on developing novel therapies for the treatment of prostate cancer, reported a corporate update and provided financial results for the fourth quarter and fiscal year ended September 30, 2024 (Press release, ESSA, DEC 17, 2024, View Source [SID1234649174]).

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"We recently made the difficult decision to terminate the clinical development of masofaniten, and withdraw the related IND and CTAs, based on an interim analysis of the data from the Phase 2 combination study, concluding that masofaniten combined with enzalutamide was unlikely to meet its primary endpoint," said David Parkinson, MD, President and CEO of ESSA. "We are currently evaluating and reviewing our strategic options focused on maximizing shareholder value and look forward to providing further updates in the near future."

Fourth Quarter Fiscal 2024 and Recent Updates

In October 2024, ESSA made the decision to terminate all clinical trials evaluating masofaniten and to withdraw the related IND and CTAs. The decision was based on the outcome of a futility analysis conducted as part of a protocol-specified interim review of the Phase 2 clinical trial evaluating masofaniten combined with enzalutamide versus enzalutamide monotherapy in patients with metastatic castration-resistant prostate cancer ("mCRPC") naïve to second-generation antiandrogens.

The interim analysis, which reviewed the Phase 2 safety, PK and efficacy data, showed that the study enzalutamide monotherapy control arm (which is the standard of care for this patient population) had a much higher rate of PSA90 response than was expected based upon historical data. In addition, there was no clear efficacy benefit seen with the combination of masofaniten plus enzalutamide compared to enzalutamide single agent. A futility analysis determined a low likelihood of meeting the prespecified primary endpoint of the study. It was therefore concluded that the study was unlikely to achieve its primary endpoint.

The combination of masofaniten plus enzalutamide was well-tolerated with no new safety signals and a safety profile similar to that seen in Phase 1 monotherapy and combination studies.

ESSA has initiated a comprehensive process to explore and review a range of strategic options focused on maximizing shareholder value, which may include, but are not limited to a merger, amalgamation, take-over, business combination, asset sale or acquisition, shareholder distribution, wind-up, liquidation and dissolution, seek new products for development, or other strategic direction. The process is expected to involve headcount and other cost reductions.

On December 12, 2024, ESSA provided a notice of termination of the License Agreement to the Licensors, notifying the Licensors that it terminated the License Agreement in accordance with its terms, effective as of December 12, 2024.
Summary Financial Results
(Amounts expressed in U.S. dollars)

Net Loss. ESSA recorded a net loss of $28.5 million for the year ended September 30, 2024 compared to a net loss of $26.6 million for the year ended September 30, 2023. For the year ended September 30, 2024, this included non-cash share-based payments of $6.5 million compared to $5.3 million for the prior year, recognized for stock options granted and vesting. Net loss for the fourth quarter ended September 30, 2024 was $6.4 million compared to a net loss of $5.5 million for the fourth quarter ended September 30, 2023.
Research and Development ("R&D") expenditures. R&D expenditures for the year ended September 30, 2024 were $21.2 million compared to $21.3 million for the year ended September 30, 2023, and include non-cash costs related to share-based payments ($1.8 million for the year ended 2024 compared to $2.7 million for the year ended 2023). R&D expenditures for the fourth quarter ended September 30, 2024 were $4.2 million compared to $5.2 million for the fourth quarter ended September 30, 2023 due to lower expenditures on preclinical and manufacturing.
General and Administration ("G&A") expenditures. G&A expenditures for the year ended September 30, 2024 were $13.2 million compared to $10.8 million for the year ended September 30, 2023, and include non-cash costs related to share-based payments of $4.7 million for the year ended 2024 compared to $2.6 million for the year ended 2023. G&A expenditures for the fourth quarter ended September 30, 2024 were $3.5 million compared to $1.9 million for the fourth quarter ended September 30, 2023. The increase for the fourth quarter was primarily due to increased share-based payments and higher salary figures.
Liquidity and Outstanding Share Capital

As of September 30, 2024, the Company had available cash reserves and short-term investments of $126.8 million and net working capital of $124.3 million. The Company has no long-term debt facilities.
As of September 30, 2024, the Company had 44,388,550 common shares issued and outstanding, and there were 2,920,000 common shares issuable upon the exercise of prefunded warrants at an exercise price of $0.0001.

On December 17, 2024 IDEAYA Biosciences, Inc. (Nasdaq: IDYA), a precision medicine oncology company committed to the discovery and development of targeted therapeutics, reported the Independent Data Monitoring Committee (IDMC) recommendation of a move-forward dose and the completion of the Part 2a dose optimization consistent with the U.S. Food and Drug Administration’s (FDA) Project Optimus guidelines for the potential registration-enabling Phase 2/3 trial evaluating the combination of darovasertib and crizotinib in the first-line (1L) setting in patients with HLA-A2-negative (HLA-A2(-)) metastatic uveal melanoma (MUM) (Press release, Ideaya Biosciences, DEC 17, 2024, View Source [SID1234649173]).

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"We are pleased with the recommendation of the IDMC and the selection of the move-forward dose for our potential registration-enabling trial evaluating the darovasertib and crizotinib combination in first-line HLA-A2(-) MUM patients. This allows us to complete the Part 2a portion of the study and seamlessly continue to enroll in Part 2b towards a potential accelerated approval based on the primary endpoint of median progression free survival," said Darrin M. Beaupre, M.D., Ph.D., Chief Medical Officer, IDEAYA Biosciences.

"The combination of darovasertib and crizotinib as first-line treatment has shown compelling preliminary clinical results in patients with HLA-A2(-) MUM. The IDMC recommendation of the move-forward dose supports the advancement of this potentially registration-enabling Phase 2/3 trial and is an important step in bringing a new treatment option to patients with MUM. Additionally, the continued rapid enrollment further validates the strong interest from physicians and patients, and highlights the significant unmet need in these patients, who historically have faced a poor prognosis," added Meredith McKean, M.D., MPH, Director, Melanoma and Skin Cancer Research at Sarah Cannon Research Institute, and clinical investigator on the potential registration-enabling clinical trial.

The darovasertib and crizotinib combination in MUM has FDA Fast Track designation and is currently being evaluated in two clinical trials: a potentially registration-enabling Phase 2/3 trial of darovasertib and crizotinib combination in first-line HLA-A2(-) MUM (NCT05987332) and a Phase 2 trial (NCT03947385). Additionally, darovasertib as neoadjuvant monotherapy is currently being evaluated in a Phase 2 trial in primary uveal melanoma (NCT05907954). IDEAYA is also finalizing a clinical trial protocol and is targeting to initiate a potential Phase 3 registration-enabling study for neoadjuvant uveal melanoma patients in the first half of 2025.

On December 17, 2024 Expert Systems, a leader in AI-powered drug discovery, reported the promising clinical results of oral once-daily lonitoclax, a next-generation BCL-2 inhibitor developed in collaboration with Lomond Therapeutics (Press release, Lomond Therapeutics, DEC 17, 2024, View Source [SID1234649172]). The results of the single ascending dose Phase 1 studies demonstrate important advantages of lonitoclax over venetoclax and venetoclax-like molecules for chronic lymphocytic leukemia (CLL), acute myeloid leukemia (AML), and potentially other oncology indications.

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Lonitoclax demonstrated no significant safety signals at exposures sufficient to achieve robust inhibition of BCL-2, as measured via ex vivo activation of caspase in primary CLL cells. Importantly, the co-administration of itraconazole—a potent CYP 3A4 inhibitor—did not significantly alter lonitoclax exposures. These results highlight a key differentiation from venetoclax and similar molecules, which require complex dose titration and ritonavir co-administration, and emphasize important advantages in safety, tolerability, and feasibility of outpatient treatment.

"Lonitoclax’s promising Phase 1 results highlight the strength of our AI-enabled platform in driving the development of next-generation therapies," said Bill Farley, Chief Business Officer at Expert Systems. "Our platform de-risks early-stage drug development by reducing time and costs while delivering data-driven insights to optimize safety and efficacy. We are proud to support Lomond Therapeutics in advancing this innovative BCL-2 inhibitor, which has the potential to transform the treatment landscape for CLL and AML patients."

About Lonitoclax

Lonitoclax is a next generation BCL-2 inhibitor that has demonstrated best-in-class molecular pharmacology with the highest selectivity against BCL2, a key pro-survival protein that is overexpressed in many cancers. To mitigate the hematologic and immune toxicities observed with venetoclax, lonitoclax was designed with a unique binding mode to improve selectivity for BCL-2 over BCL-XL. In addition, a shorter half-life and reduced P4503A4 inhibition properties were built into the molecule to mitigate tumor lysis syndrome and drug accumulation risk, respectively. Lonitoclax has demonstrated monotherapy activity in pre-clinical models, as well as synergistic activity when combined with azacitidine, FLT3 inhibitors, and menin inhibitors in AML xenograft models. Unlike venetoclax, lonitoclax had minimal immunosuppressive activity on B cells, CD8 T cells, and NK cells in preclinical models.

On December 17, 2024 A2A Pharmaceuticals, Inc. ("A2A" or "the company"), a clinical-stage pioneering biopharmaceutical company focused on developing innovative cancer therapies, reported progress in its clinical studies exploring TACC3 (Transforming Acidic Coiled-Coil 3) PPI inhibition in patients with ovarian cancer, triple-negative breast cancer (TNBC), and endometrial cancer (Press release, A2A Pharmaceuticals, DEC 17, 2024, View Source [SID1234649167]).

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A2A has progressed into cohort 4, an important inflection point in its Phase 1 clinical trial to assess the safety and efficacy of its lead TACC3 inhibitor, AO-252. Early results have shown strong safety profiles with the potential for a wide therapeutic index in these patient populations.

"We are excited about the advancements in our TACC3 program and its potential for patients with challenging cancer diagnoses. The company is continually exploring collaborations and partnerships to accelerate development timelines and enhance patient access to cutting-edge treatments," said Sotirios Stergiopoulos, M.D., CEO of A2A.

"While our current focus with AO-252 is on addressing the unmet needs in ovarian, TNBC, and endometrial cancers, we are equally excited about its potential to benefit patients in additional indications in the near future," added Robbin Frnka, Vice President of Clinical Operations."

The selected cancers are characterized by limited treatment options and high rates of recurrence in patients. A2A’s TACC3 PPI inhibitor is designed to disrupt critical cellular mechanisms involved in cancer cell proliferation, providing a much-needed new avenue of treatment for patients battling these aggressive malignancies.

"This trial represents a promising step forward in delivering therapies that could impact the standard of care for patients," said Alex Spira, M.D., principal investigator of Next Oncology Virginia. "A2A Pharmaceuticals shows dedication to supporting the cancer community by advancing novel therapies that target the underlying biology of tumors."

Beyond these indications, pre-clinical studies suggest A2A’s TACC3 PPI inhibitor may also show efficacy in other solid tumors, including gastric, prostate cancers, and sarcomas, etc. Ongoing research efforts are focused on expanding the indication spectrum and optimizing treatment regimens for diverse cancer types.

On December 17, 2024 Gilead Sciences, Inc. (Nasdaq: GILD) and Terray Therapeutics, Inc. reported that the companies have entered into a strategic collaboration to discover and develop novel, small molecule therapies across multiple targets (Press release, Gilead Sciences, DEC 17, 2024, View Source [SID1234649163]).

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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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Terray’s tNova platform combines high-throughput chemical experimentation and computational analysis with a generative AI-driven drug discovery engine. The company’s iterative approach applies AI-empowered methods to an extensive library of quantitative, purpose-built, structure activity data to find the right molecules to solve complex problems in drug discovery.

"Next-generation, AI-driven platforms using custom-generated large, relevant data sets will serve as important tools in our efforts to shape the future of drug discovery in our ongoing pursuit of innovative treatments across our therapeutic areas of focus," said Flavius Martin, M.D., Executive Vice President, Research, Gilead Sciences. "We are excited to collaborate with Terray and explore how their integrated discovery platform will complement our own internal research capabilities and expertise."

"We’re proud to strategically partner with Gilead," said Jacob Berlin, Ph.D., Chief Executive Officer, Terray Therapeutics. "We’re very excited to put tNova’s unique blend of experimentation and computation to work alongside the deep expertise of our collaborators at Gilead to find transformational small molecule therapeutics that bring relief to patients in need."

Terms of the Agreement

Under the terms of the agreement, Terray will utilize the Terray tNova platform to discover and develop small molecule compounds against a set of targets selected by Gilead. If Gilead exercises its option to exclusively license the compounds directed to a target, Gilead will be responsible for further development and commercialization activities for products resulting from the collaboration. Terray will receive an upfront payment and is eligible to receive milestone payments associated with the achievement of preclinical, clinical, and sales milestones as well as tiered royalties on net sales of products commercialized by Gilead in connection with the collaboration.

Gilead does not exclude acquired IPR&D expenses from its non-GAAP financial measures. This transaction with Terray is expected to reduce Gilead’s GAAP and non-GAAP 2024 EPS by approximately $0.01.