On August 27, 2024 Telix Pharmaceuticals Limited (ASX: TLX, Telix, the Company) reported that it has submitted a New Drug Application (NDA) to the United States (U.S.) Food and Drug Administration (FDA) for TLX101-CDx, (Pixclara[1], 18F-floretyrosine or 18F-FET), an investigational PET[2] agent for the characterisation of progressive or recurrent glioma (brain cancer) from treatment related changes in both adult and pediatric patients (Press release, Telix Pharmaceuticals, AUG 27, 2024, View Source [SID1234646129]).

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Given the potential to address significant unmet medical need, Pixclara1 has been granted Orphan Drug[3] and Fast Track[4] designation by the FDA, which facilitates expedited review and closer consultation with the agency during the review process. FET PET (Pixclara1) is already included in international clinical practice guidelines for the imaging of gliomas[5], however there is currently no FDA-approved targeted amino acid PET agent for adult and pediatric brain cancer imaging commercially available in the U.S.

There is a critical unmet need to improve the diagnosis and management of glioma, particularly in the post-treatment setting. With low survival rates and the need to make rapid decisions, precision imaging is paramount. Subject to regulatory approval, Pixclara1 has the potential to address this need, enabling patients to receive greater clarity in their diagnosis and treatment decision making. Pixclara1 is also being developed as the "companion" theranostic imaging agent for TLX101, Telix’s investigational neuro-oncology drug candidate, which targets the same amino acid transporter mechanism with therapeutic targeted radiation.

Kevin Richardson, Chief Executive Officer, Telix Precision Medicine, stated, "Gliomas are the most common primary brain tumours of the central nervous system. Conventional imaging with MRI[6] often yields inconclusive results in characterising recurrent disease and therefore delays time-sensitive decision making4. Limitations of conventional imaging techniques include the lack of biological specificity, dependency on blood-brain barrier disruption, and an inherent inability to differentiate between tumour progression or treatment-related causes[7]. Telix’s filing of this NDA for Pixclara1 is an important milestone, reflecting our commitment to improved and accessible neuro-oncology imaging in the U.S., and taking us one step closer to commercial availability in 2025, subject to FDA approval."

About TLX101-CDx

TLX101-CDx (Pixclara1) is a PET imaging agent, which has been granted fast track and orphan drug designations by the FDA as an imaging agent for the characterisation of glioma. TLX101-CDx targets membrane transport proteins known as LAT1 and LAT2[8]. This enables TLX101-CDx to be potentially utilised as a companion diagnostic agent to TLX101 (4-L-[131I] iodo-phenylalanine, or 131I-IPA), Telix’s LAT1-targeting investigational glioblastoma (GBM) therapy, currently under investigation in the IPAX-2[9] and IPAX-Linz[10] studies.

About gliomas in the U.S.

Gliomas are very diffusely infiltrative tumours that affect the surrounding brain tissue. They are the most common form of central nervous system (CNS) neoplasm that originates from glial cells, accounting for approximately 30% of all brain and CNS tumours and 80% of all malignant brain tumours[11]. In the U.S., there are six cases of gliomas diagnosed per 100,000 people every year. GBM is a high-grade glioma and the most common and aggressive form of primary brain cancer, with approximately 22,000 new cases diagnosed annually in the U.S.[12]. The mainstay of treatment for GBM comprises surgical resection, followed by combined radiotherapy and chemotherapy. Despite such treatment, recurrence occurs in almost all patients[13], with an expected survival duration of 12-15 months from diagnosis.

On August 27, 2024 (the "Closing Date"), Arcus Biosciences, Inc. (the "Company") reported to have entered into a Loan and Security Agreement (the "LSA"), by and among the Company, the several banks and other financial institutions or entities party thereto, as lenders, and Hercules Capital, Inc. ("Hercules"), as administrative agent and collateral agent (Filing, 8-K, Arcus Biosciences, AUG 27, 2024, View Source [SID1234646113]).

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The LSA provides a secured term loan facility of up to $250.0 million (collectively, the "Term Loans"), consisting of: (a) an initial $50.0 million tranche of term loans, which was funded on the Closing Date; (b) an additional tranche of term loans in an aggregate amount of $50.0 million that is available at the Company’s sole option, subject to customary terms and conditions, through June 15, 2025; (c) an additional tranche of term loans in an aggregate amount of $50.0 million that is available at the Company’s sole option, subject to customary terms and conditions, through March 15, 2026 (the amounts listed in (a), (b) and (c) above, the "Initial Tranches") and (d) an additional tranche of term loans in an aggregate amount of $100.0 million (the "Final Tranche"), which will be available at the lenders’ sole option, subject to customary terms and conditions, in $25.0 million increments. On the Closing Date, the Company paid an initial facility charge for the Initial Tranches equal to $1.125 million.

Borrowings under the LSA bear interest at a per annum rate equal to: (a) in cash, the greater of either (i) the Prime Rate (as reported in the Wall Street Journal) plus 1.95% and (ii) 10.45%. The Term Loans are repayable in monthly interest-only payments until September 1, 2028 (the "Interest-Only Payment Period"). The Company may extend the Interest-Only Payment Period an additional 12 months if (i) no default or event of default exists under the LSA and (ii) by August 27, 2028, the U.S. Food and Drug Administration has approved either a Biologics License Application or New Drug Application ("Milestone I"). After the expiration of the Interest-Only Payment Period, the Term Loans are repayable in equal monthly payments of principal and accrued interest until maturity.
The Term Loans will mature on September 1, 2029 (the "Maturity Date"). The Company may extend the Maturity Date up to an additional 12 months if (i) no default or event of default exists and (ii) the Company has accomplished two of the following events ("Milestone II"): (a) dosing the first patient in a pivotal phase 3 study of casdatifan for the treatment of renal cell carcinoma; (b) dosing the first patient in a pivotal phase 3 study of quemliclustat in patients with advanced pancreatic cancer; or (c) dosing the first patient in a pivotal phase 3 study of etrumadenant in patients with metastatic colorectal cancer.

At the Company’s option, the Company may prepay all or a portion of the outstanding Term Loans, subject to a prepayment premium equal to (a) 3.0% of the Term Loans being prepaid if the prepayment occurs during the 12 months following the Closing Date; (b) 2.0% of the Term Loans being prepaid if the prepayment occurs after the 12 month anniversary of the Closing Date but on or prior to the 24 month anniversary of the Closing Date; and (c) 1.0% of the Term Loans being prepaid if the prepayment occurs at least 24 months following the Closing Date and prior to the Maturity Date. In addition, the Company will pay an end of term charge of 7.75% upon the prepayment or repayment of the Term Loans and a facility charge of 0.75% upon any draws of the Term Loans from the Final Tranche.

The Term Loans are secured by a lien on substantially all of the assets of the Company other than any assets subject to an option held by Gilead Sciences, Inc. or Taiho Pharmaceutical Co., Ltd. The LSA includes a financial covenant that requires the Company to maintain, at all times during which the Company’s market capitalization is at or below $1.20 billion, "Qualified Cash" (defined as cash in accounts subject to control agreements minus any accounts payable not paid after the 120th day) in an amount greater than or equal to the outstanding principal amount of the Term Loans, multiplied by 50% (the "Qualified Cash Requirement Threshold"). The Qualified Cash Requirement Threshold will be decreased (a) to 40% upon accomplishing Milestone I and (b) to 35% upon accomplishing Milestone II.
In addition, the LSA includes customary affirmative and negative covenants and representations and warranties, including a covenant against the occurrence of a "change in control," financial reporting obligations, and certain limitations on indebtedness, liens, investments, distributions (including dividends), collateral, transfers, mergers or acquisitions, taxes, corporate changes, and bank accounts. The LSA also includes customary events of default, including payment defaults, breaches of covenants following any applicable cure period, the occurrence of certain events that could reasonably be expected to have a "material adverse effect" as set forth in the LSA, cross acceleration to third-party indebtedness and certain events relating to bankruptcy or insolvency. Upon the occurrence of an event of default, Hercules may declare all outstanding obligations immediately due and payable and take such other actions as set forth in the LSA.

The foregoing is only a brief description of the material terms of the LSA does not purport to be a complete description of the rights and obligations of the parties thereunder and is qualified in its entirety by reference to such agreement, which will be filed as an exhibit to the Company’s Quarterly Report on Form 10-Q for the period ended September 30, 2024.

On August 27, 2024 Illumina, Inc. (NASDAQ: ILMN), a global leader in DNA sequencing and array-based technologies, reported Food and Drug Administration (FDA) approval of its in vitro diagnostic (IVD) TruSight Oncology (TSO) Comprehensive test and its first two companion diagnostic (CDx) indications (Press release, Illumina, AUG 27, 2024, View Source [SID1234646130]). This single test interrogates over 500 genes to profile a patient’s solid tumor, helping to increase the likelihood of identifying an immuno-oncology biomarker or clinically actionable biomarkers that enable targeted therapy options or clinical trial enrollment. TSO Comprehensive is FDA approved as a CDx to identify adult and pediatric patients with solid tumors who are positive for neurotrophic tyrosine receptor kinase (NTRK) gene fusions that may benefit from treatment with Bayer’s VITRAKVI (larotrectinib). The test is also approved to identify adult patients with locally advanced or metastatic rearranged during transfection (RET) fusion-positive non-small-cell lung cancer (NSCLC) that may benefit from treatment with Lilly’s RETEVMO (selpercatinib).

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"FDA approval for TruSight Oncology Comprehensive with accompanying companion diagnostics marks an awaited milestone for our oncology customers and community," said Everett Cunningham, chief commercial officer of Illumina. "We are committed to partnering with industry leaders like Bayer and Lilly to advance cancer diagnostics and help broaden access to precision oncology for more patients."

A CDx test may identify whether a patient’s tumor has a specific gene change or biomarker that can be targeted by a therapy, helping to determine if a patient should receive the therapy. Most CDx tests are specific to one type of cancer, but TSO Comprehensive is approved for use across solid tumor indications for the NTRK CDx, helping to maximize the chances of finding actionable information from each patient’s biopsy.

NTRK gene fusions are rare across most solid cancer tumor types (~0.1%–0.3%), and can be challenging to detect, given that these genes can fuse with different partners, many of which were previously unknown. TSO Comprehensive also interrogates RNA and thus can identify a broad range of known and novel gene fusion partners across all three NTRK gene fusions, NTRK1, NTRK2, and NTRK3. Bayer’s VITRAKVI (larotrectinib) is a highly selective TRK inhibitor approved for use in patients with TRK fusion cancer, in accordance with therapeutic labeling.

NSCLC is one of the most common types of lung cancer and the leading cause of cancer-related deaths globally. The expansive actionable biomarker landscape in NSCLC has driven the need for broad molecular profiling to enable a complete view of a patient’s disease to better guide clinical management. The oncogenic activation of RET fusion-positive NSCLC by gene fusions is a primary driver in NSCLC, occurring in up to 2% of cases. Lilly’s RETEVMO (selpercatinib) is a highly selective and potent RET kinase inhibitor in locally advanced or metastatic NSCLC. TSO Comprehensive enables broad characterization and simultaneous detection of multiple prognostic and predictive biomarkers such as RET, genomic signatures such as tumor mutational burden, and emerging biomarkers within NSCLC in a single test.

"Through research conducted globally, there is a significant body of evidence demonstrating the clinical utility of comprehensive genomic profiling for patients with advanced cancer," said Vivek Subbiah, MD, chief, Early-Phase Drug Development at Sarah Cannon Research Institute. "Illumina’s newest distributable IVD kit for comprehensive genomic profiling and accompanying CDx enable another valuable clinical tool for the oncology community to match patients with targeted therapies that can vastly improve their journey and outcomes."

TSO Comprehensive will begin shipping to customers this year. Comprehensive genomic profiling assays with CDx claims for solid tumors, like TSO Comprehensive, are reimbursable under a Centers for Medicare & Medicaid Service national coverage determination.

Illumina has a growing pipeline of CDx claims under development through partnerships with pharmaceutical companies, which will be added to TSO Comprehensive following appropriate regulatory approvals. These CDx claims will help unlock groundbreaking targeted therapies and immunotherapies to make a difference in the lives of patients with cancer.

A separate CE-marked version of TSO Comprehensive is already available in Europe, launched in 2022. To learn more about TruSight Oncology Comprehensive.About TruSight Oncology Comprehensive

TruSight Oncology Comprehensive is a qualitative in vitro diagnostic test that uses targeted next-generation sequencing to detect variants in 517 genes using nucleic acids extracted from formalin-fixed, paraffin-embedded (FFPE) tumor tissue samples from cancer patients with solid malignant neoplasms using the Illumina NextSeq 550Dx Instrument. The test can be used to detect single nucleotide variants, multi-nucleotide variants, insertions, and deletions from DNA, and fusions in 24 genes and splice variants in one gene from RNA. The test also reports a Tumor Mutational Burden (TMB) score.

The test is intended to be used as a companion diagnostic to identify cancer patients who may benefit from treatment with the targeted therapies listed in Table 1, in accordance with the approved therapeutic product labeling.

In addition, the test is intended to provide tumor profiling information for use by qualified health care professionals in accordance with professional guidelines in oncology for patients with solid malignant neoplasms. Genomic findings other than those listed in Table 1 of the intended use statement are not conclusive or prescriptive for labeled use of any specific therapeutic product.

Table 1: Companion diagnostic indications

Tumor Type

Biomarker(s) Detected

Therapy

Solid Tumors

NTRK1/2/3 fusions

VITRAKVI (larotrectinib)

Non-Small Cell Lung Cancer

RET fusions

RETEVMO (selpercatinib)

On August 26, 2024 Notable Labs, Ltd. (Nasdaq: NTBL) ("Notable", "Notable Labs" or the "Company"), a clinical-stage precision oncology company developing new cancer therapies identified by its Predictive Medicine Platform (PMP), reported that Thomas A. Bock, MD has resigned from his positions as Chief Executive Officer (CEO) and member of the Board of Directors of the Company, effective today (Press release, Notable Labs, AUG 26, 2024, View Source [SID1234646097]).

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Joseph Wagner, PhD, the Company’s Chief Scientific Officer (CSO), has been appointed as interim CEO. The Board of Directors has initiated a search process for Dr. Bock’s successor.

"On behalf of the Board and the entire Notable team, I want to extend our deepest gratitude to Thomas for his visionary leadership and tireless dedication to the Company. Under his leadership, Notable transformed from a private diagnostic start-up to a publicly-traded clinical-stage therapeutic-focused leader in Predictive Medicine and delivered industry-leading results from platform-validating clinical trials in hematologic cancers. We are confident that the strong foundation Thomas built will lead to continued progress, starting with the initiation of the Phase 2 clinical program for volasertib, expected in the coming months," said Tuomo Pätsi, Chairman of the Board. "As we search for Thomas’ successor, we look forward to working with Joe to continue Notable’s work to revolutionize the use of predictive medicine in cancer care."

"I am especially proud of Notable’s world-class team and how far the Company has come in developing PMP as a novel precision medicine tool. I believe the re-designed volasertib development program, which merges biology and technology through enhanced trial design and the use of PMP, has the potential to improve treatment outcomes for patients with AML," said Dr. Bock. "With our FDA-cleared Phase 2 program nearing significant clinical milestones, I am optimistic for Notable’s future and thankful to our team, Board, investors, advisors, and all partners for their shared commitment and the sense of urgency that patients deserve."

Dr. Bock will continue as a consultant to the Company, advising the Board of Directors and offering his expertise and guidance on the Company’s next phase.

About Volasertib

Volasertib is a PLK-1 inhibitor with demonstrated activity in AML and other tumor types, including solid tumors, with significant unmet medical need. Building on the performance of volasertib on PMP, an important and proprietary step during Notable’s targeted in-licensing strategy and decision making, Notable will utilize its PMP to predict volasertib-responsive patients prior to their treatment, with the goal of selectively enrolling and treating those predicted responders, increasing volasertib’s response rates and overall patient outcomes, and fast-tracking volasertib’s remaining clinical development in this patient population. Volasertib was originally developed and manufactured by Boehringer Ingelheim and previously granted Breakthrough Therapy designation by the FDA. Notable in-licensed volasertib and obtained exclusive worldwide development and commercialization rights, except for certain rare pediatric cancers.

On August 26, 2024 ORIC Pharmaceuticals, Inc. (Nasdaq: ORIC), a clinical stage oncology company focused on developing treatments that address mechanisms of therapeutic resistance, reported that management will participate in the following investor conferences in September (Press release, ORIC Pharmaceuticals, AUG 26, 2024, View Source [SID1234646099]):

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2024 Wells Fargo Healthcare Conference – Participating in a fireside chat on Thursday, September 5, 2024, at 8:00 a.m. ET
Baird 2024 Global Healthcare Conference (Available to conference attendees only) – Participating in a fireside chat on Tuesday, September 10, 2024, at 10:50 a.m. ET.
2024 Cantor Global Healthcare Conference – Participating in a fireside chat on Thursday, September 19, 2024, at 8:35 a.m. ET
Live webcasts of the Wells Fargo and Cantor discussions will be available through the investor section of the company’s website at www.oricpharma.com. Replays of the webcasts will be available for 90 days following the events.