On December 22, 2023 Clarity Pharmaceuticals (ASX: CU6) ("Clarity"), a clinical stage radiopharmaceutical company with a mission to develop next-generation products that improve treatment outcomes for children and adults with cancer, reported that the first patient has been dosed in its pivotal Phase III 64Cu-SAR-bisPSMA diagnostic trial in prostate cancer, CLARIFY (NCT06056830)1, at the Urology Cancer Center / XCancer Omaha, NE (Press release, Clarity Pharmaceuticals, DEC 22, 2023, View Source [SID1234638784]).

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The aim of the CLARIFY study is to assess the diagnostic performance of 64Cu-SAR-bisPSMA to detect regional nodal metastases in participants with high-risk prostate cancer prior to radical prostatectomy. The study will recruit 383 participants at multiple clinical sites across the United States and Australia.

Evaluation of the first patient is taking place over 2 imaging timepoints, day 1 (day of administration) and day 2 (approximately 24 hours post administration) and the patient will be followed up as per protocol. Subsequent patients will be evaluated in the same manner. As a pivotal trial, the final study results are intended to provide sufficient evidence to support an application to the FDA for approval of 64Cu-SAR-bisPSMA as a new diagnostic imaging agent in prostate cancer in pre-prostatectomy patients.

Clarity’s Executive Chairperson, Dr Alan Taylor, commented, "We are excited to have successfully dosed the first participant in the CLARIFY trial with our optimised SAR-bisPSMA agent. The trial is driven by the compelling findings from our PROPELLER trial (NCT04839367)2,3 which highlighted the robust safety profile and superior performance of 64Cu-SAR-bisPSMA compared to standard of care imaging (68Ga-PSMA-11) with imaging on the day of administration, with two to three times the amount of product taken up in the lesions2,3. The longer half-life of copper-64 based diagnostics, in comparison to the currently used gallium-68 and fluorine-18 based products, also allows for delayed imaging. These unique features have the potential to enable detection of additional lesions compared to standard of care imaging and may address the significant shortfall in sensitivity of these agents. Additionally, the extended shelf-life of 64Cu-SAR-bisPSMA of up to 48 hours, in contrast to the short shelf-life of currently available PSMA PET tracers, not only enhances scheduling flexibility for clinics, but also addresses a critical need for diagnostics in geographic areas with limited access to the current generation of radiopharmaceuticals.

"Clarity is steadfast in addressing the high unmet need for diagnostics and therapies in the prostate cancer domain. Our optimism is rooted in the belief that our SAR-bisPSMA product can redefine diagnostic standards and improve patient outcomes. As we progress with the CLARIFY trial, we anticipate validating and building upon the positive data accumulated so far. Our vision is a future where enhanced diagnostic tools empower clinicians to make more informed decisions, ultimately shaping the optimal course of treatment for their patients.

"Although the current generation of PSMA-based radiopharmaceuticals is broadening the horizons of prostate cancer management and offering new treatment pathways for patients in need, we have seen in Clarity’s PROPELLER trial that 64Cu-SAR-bisPSMA has the potential of really changing this paradigm and outcomes for patients. We look forward to exploring and confirming these benefits in the CLARIFY trial."

About the CLARIFY trial

CLARIFY derives from "Positron Emission Tomography using 64Cu-SAR-bisPSMA in participants with high-risk PC prior to radical prostatectomy: A prospective, single-arm, multi-centre, blinded-review, Phase III diagnostic performance study". It is a non-randomised, open-label clinical trial in 383 participants. The primary aim of the Phase III trial is to assess the diagnostic performance of 64Cu-SAR-bisPSMA PET to detect regional nodal metastases. Furthermore, the safety, tolerability, and consistency of 64Cu-SAR-bisPSMA will be assessed. All patients will receive a single administration of 200MBq 64Cu-SAR-bisPSMA. Evaluation will take place over 2 imaging timepoints, Day 1 (day of administration) and Day 2 (approximately 24 hours post administration).

About SAR-bisPSMA

SAR-bisPSMA derives its name from the word "bis", which reflects a novel approach of connecting two PSMA-targeting agents to Clarity’s proprietary sarcophagene (SAR) technology that securely holds copper isotopes inside a cage-like structure, called a chelator. Unlike other commercially available chelators, the SAR technology prevents copper leakage into the body. SAR-bisPSMA is a TCT that can be used with isotopes of copper-64 (Cu-64 or 64Cu) for imaging and copper-67 (Cu-67 or 67Cu) for therapy.

64Cu-SAR-bisPSMA and 67Cu-SAR-bisPSMA are unregistered products. Individual results may not represent the overall safety and efficacy of the products. A clinical development program is currently underway to assess the efficacy and safety of these products. There is no guarantee that these products will become commercially available.

About Prostate Cancer

Prostate cancer is the second most common cancer diagnosed in men globally and the fifth leading cause of cancer death worldwide4. The American Cancer Institute estimates in 2023 there will be 288,300 new cases of prostate cancer in the US and around 34,700 deaths from the disease.

On December 22, 2023 enGene Holdings Inc. ("enGene,"Nasdaq: ENGN), a clinical-stage genetic medicines company whose lead EG-70 program is in a pivotal study for BCG-unresponsive non-muscle invasive bladder cancer (NMIBC), reported that it has entered into an amended USD $50 million loan agreement (the "Loan Agreement") with Hercules Capital, Inc. (NYSE: HTGC) ("Hercules") (Press release, enGene, DEC 22, 2023, View Source [SID1234638783]). Under the Loan Agreement, which has a term of four years, $22.5 million has been advanced to enGene under a non-revolving term loan and, subject to certain clinical and financial milestones, up to a further $27.5 million in loan proceeds may be available subject to satisfaction of certain terms and conditions.

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"We are thrilled to expand our relationship with Hercules Capital and obtain additional resources to support our development efforts," said Jason Hanson, Chief Executive Officer of enGene. "We believe that EG-70 could transform how patients with BCG-unresponsive NMIBC are managed, and the proceeds from this term loan facility will further support the development of this program in BCG-unresponsive NMIBC and additional clinical applications. We expect that the capital obtained will meaningfully extend the Company’s cash runway, with cash supporting operations well beyond the anticipated EG-70 interim data readout."

"Hercules Capital is pleased to collaborate once again with enGene as it advances EG-70 as an entirely new genetic medicine approach to treat NMIBC. This new, increased commitment from Hercules exemplifies our approach as long-term capital partners to our portfolio companies and reflects our dedication to financing innovative life sciences companies through development and into commercialization," said R. Bryan Jadot, Senior Managing Director and Group Head of Hercules Capital. The proceeds of the Term Loan Facility will be used for working capital and general corporate purposes of the Company, as well as to refinance enGene’s existing indebtedness under the original loan agreement with Hercules dated December 30, 2021.

Under the terms of the agreement, the principal amount outstanding and all accrued but unpaid interest under the Term Loan Facility shall be repaid on or before January 1, 2028 (or such later dates as to which the maturity date may be extended from time to time in accordance with the terms of the Loan Agreement).

On December 22, 2023 Daiichi Sankyo (TSE: 4568) and Merck (known as MSD outside of the United States and Canada) (NYSE: MRK) reported that the U.S. Food and Drug Administration (FDA) has accepted and granted Priority Review to the Biologics License Application (BLA) for patritumab deruxtecan (HER3-DXd) for the treatment of adult patients with locally advanced or metastatic EGFR-mutated non-small cell lung cancer (NSCLC) previously treated with two or more systemic therapies (Press release, Daiichi Sankyo, DEC 22, 2023, View Source [SID1234638782]).

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The Prescription Drug User Fee Act (PDUFA) date, the FDA action date for their regulatory decision, is June 26, 2024. The Priority Review follows receipt of Breakthrough Therapy Designation granted by the FDA in December 2021.

The FDA grants Priority Review to applications for medicines that, if approved, would offer significant improvements over available options by demonstrating safety or efficacy improvements, preventing serious conditions or enhancing patient compliance. The BLA is being reviewed under the Real-Time Oncology Review (RTOR) program, an initiative of the FDA which is designed to bring safe and effective cancer treatments to patients as early as possible. RTOR allows the FDA to review components of an application before submission of the complete application.

Patritumab deruxtecan is a specifically engineered potential first-in-class HER3 directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo and being jointly developed and commercialized by Daiichi Sankyo and Merck.

The BLA is based on the primary results from the HERTHENA-Lung01 pivotal phase 2 trial and data results presented at the IASLC 2023 World Conference on Lung Cancer (#WCLC23), which were simultaneously published in the Journal of Clinical Oncology.

In HERTHENA-Lung01, patritumab deruxtecan was studied in 225 patients with EGFR-mutated locally advanced or metastatic NSCLC following disease progression with an EGFR TKI and platinum-based chemotherapy, which demonstrated an objective response rate (ORR) of 29.8% (95% CI: 23.9-36.2), including one complete response and 66 partial responses. The median duration of response was 6.4 months (95% CI: 4.9-7.8). The safety profile of patritumab deruxtecan observed in HERTHENA-Lung01 was consistent with previous phase 1 clinical trials in NSCLC with a treatment discontinuation rate of 7.1% due to treatment-emergent adverse events (TEAEs). Grade 3 or higher TEAEs occurred in 64.9% of patients. The most common (≥5%) grade 3 or higher TEAEs were thrombocytopenia (21%), neutropenia (19%), anemia (14%), leukopenia (10%), fatigue (6%), hypokalemia (5%) and asthenia (5%). Twelve patients (5.3%) had confirmed treatment-related interstitial lung disease (ILD) as determined by an independent adjudication committee. One grade 5 ILD event was observed.

"The FDA’s prioritization of the BLA submission reflects the strength of the data from HERTHENA-Lung01 and emphasizes the need to provide new options to patients with locally advanced or metastatic EGFR-mutated non-small cell lung cancer previously treated with two or more systemic therapies," said Ken Takeshita, MD, Global Head, R&D, Daiichi Sankyo. "If approved, patritumab deruxtecan could become the first HER3 directed medicine approved in the US and the second DXd antibody drug conjugate approved from Daiichi Sankyo’s oncology pipeline."

"The acceptance of the BLA submission of patritumab deruxtecan marks an important step in potentially bringing this new medicine to previously treated patients with EGFR-mutated non-small cell lung cancer who often experience recurrence and have few remaining treatment options," said Marjorie Green, MD, Senior Vice President and Head of Late-Stage Oncology, Global Clinical Development, Merck Research Laboratories. "Today is the first of many important milestones from our collaboration with Daiichi Sankyo, as we work together to bring new and potentially first-in-class antibody drug conjugates to people living with cancer."

About HERTHENA-Lung01
HERTHENA-Lung01 is a global, multicenter, open-label, two-arm phase 2 trial evaluating the safety and efficacy of patritumab deruxtecan in patients with EGFR-mutated locally advanced or metastatic NSCLC following disease progression with an EGFR TKI and platinum-based chemotherapy. Patients were randomized 1:1 to receive 5.6 mg/kg (n=225) or an uptitration regimen (n=50). The uptitration arm was discontinued as the dose of 5.6 mg/kg of patritumab deruxtecan was selected following a risk-benefit analysis conducted from the phase 1 trial assessing the doses in a similar patient population.

The primary endpoint of HERTHENA-Lung01 was ORR as assessed by blinded independent central review (BICR). Secondary endpoints included duration of response, progression-free survival (PFS), disease control rate, and time to response – all assessed by both BICR and investigator assessment – as well as investigator-assessed ORR, overall survival, safety and tolerability.

HERTHENA-Lung01 enrolled patients in Asia, Europe, North America and Oceania. For more information about the trial, visit ClinicalTrials.gov.

About EGFR-Mutated Non-Small Cell Lung Cancer
Lung cancer is the second most common cancer and the leading cause of cancer-related deaths worldwide.1 NSCLC accounts for approximately 85% of all lung cancers – 55% having distant spread at diagnosis – with EGFR mutations occurring in 14% to 38% of all NSCLC tumors worldwide.2,3,4

About HER3
HER3 is a member of the EGFR family of receptor tyrosine kinases.5 It is estimated that about 83% of primary NSCLC tumors and 90% of advanced EGFR-mutated tumors express HER3 after prior EGFR TKI treatment.6,7 There is currently no HER3 directed therapy approved for the treatment of any cancer.

About Patritumab Deruxtecan
Patritumab deruxtecan (HER3-DXd) is an investigational HER3 directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC technology, patritumab deruxtecan is composed of a fully human anti-HER3 IgG1 monoclonal antibody attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers.

Patritumab deruxtecan was granted Breakthrough Therapy Designation by the U.S. Food and Drug Administration in December 2021 for the treatment of patients with EGFR-mutated locally advanced or metastatic NSCLC with disease progression on or after treatment with a third-generation TKI and platinum-based therapies.

Patritumab deruxtecan is currently being evaluated as both a monotherapy and in combination with other therapies in a global development program, which includes HERTHENA-Lung02, a phase 3 trial versus platinum-based chemotherapy in patients with EGFR-mutated locally advanced or metastatic NSCLC following disease progression on or after treatment with a third-generation EGFR TKI; a phase 1 trial in combination with osimertinib in EGFR-mutated locally advanced or metastatic NSCLC; and a phase 1 trial in previously treated patients with advanced NSCLC. A phase 1/2 trial in HER3 expressing metastatic breast cancer also has been completed.

On December 22, 2023 Tyra Biosciences, Inc. (the Company) reported that it has initiated and dosed the first patient in the SURF201 Phase 1 study of TYRA-200. The SURF201 study is currently enrolling and dosing adults with unresectable locally advanced/metastatic intrahepatic cholangiocarcinoma and other advanced solid tumors with activating FGFR2 gene alterations (Press release, Tyra Biosciences, DEC 22, 2023, View Source [SID1234638781]). SURF201 (Study in PrevioUsly treated and Resistant FGFR2+ Cholangiocarcinoma and Other Advanced Solid Tumors) (NCT06160752), is a Phase 1/2 multi-center, open label study designed to evaluate the safety, tolerability, and pharmacokinetics (PK) of TYRA-200 and determine the optimal and maximum tolerated doses (MTD), as well as evaluate the preliminary antitumor activity of TYRA-200.

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In addition, the Part A Phase 1 portion of the SURF301 study of TYRA-300 in oncology continues to dose escalate and has cleared multiple dose cohorts that are above the anticipated dose(s) planned for use in the Phase 2 pediatric achondroplasia (ACH) study. Current expansion cohorts in Part B are at dose level(s) anticipated to be evaluated in oncology. The Company expects to submit initial results from the SURF301 Phase 1 portion for presentation at a scientific congress in 2024.

The Company also plans to submit an Investigational New Drug (IND) application to the FDA in the second half of 2024 for the initiation of a randomized Phase 2 clinical trial with multiple dose cohorts of TYRA-300 for children with ACH. The primary objective of this study is to assess safety and tolerability in children with ACH and determine the dose(s) for further development. Secondary objectives will include evaluating change in growth velocity, growth proportionality and pharmacokinetics, as well as an assessment of quality of life and evaluation of biomarkers indicating dose-response relationships to TYRA-300. The Company’s expectation is that the study will initially evaluate treatment naïve children ages 5-12 to determine optimal dose ranges and will also include a separate analysis of children ages 5-12 with ACH who have not responded to a prior growth accelerating therapy.

On December 22, 2023 Theseus Pharmaceuticals, Inc. (NASDAQ: THRX) ("Theseus" or the "Company"), a clinical-stage biopharmaceutical company focused on improving the lives of cancer patients through the discovery, development, and commercialization of transformative targeted therapies, reported that it has entered into a definitive merger agreement (the "Merger Agreement") whereby Concentra Biosciences, LLC ("Concentra") will acquire Theseus for a price per share of Theseus common stock ("Theseus common stock") of between $3.90 and $4.05 in cash, consisting of (i) a base cash price of $3.90 per share (the "Base Price") and (ii) an additional cash amount of not more than $0.15 per share at the closing of the merger (together with the Base Price, the "Cash Amount"), plus one non-tradeable contingent value right ("CVR") representing the right to receive 80% of the net proceeds from any license or disposition of Theseus’ programs effected within 180 days of closing of the merger and 50% of the potential aggregate value of certain specified potential cost savings realized within 180 days of the close of the merger, pursuant to a Contingent Value Rights Agreement (the "CVR Agreement") (Press release, Theseus Pharmaceuticals, DEC 22, 2023, View Source [SID1234638780]).

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Following a thorough review process conducted with the assistance of its legal and financial advisors, Theseus’ Board of Directors has determined that the acquisition by Concentra – of which Tang Capital Partners, LP is the controlling shareholder – is in the best interests of all Theseus shareholders, and has unanimously approved the Merger Agreement.

Pursuant and subject to the terms of the Merger Agreement, a wholly owned subsidiary of Concentra will commence a tender offer (the "Offer") by January 9, 2024 to acquire all outstanding shares of Theseus common stock. Closing of the Offer is subject to certain conditions, including the tender of Theseus common stock representing at least a majority of the total number of outstanding shares; the availability of at least $187.6 million of cash, net of transaction costs, wind-down costs and other liabilities, at closing, and other customary closing conditions. Theseus shareholders holding approximately 59% of Theseus common stock have signed support agreements under which such shareholders agreed to tender their shares in the Offer and support the merger. The acquisition is expected to close in February 2024.

Advisors

Leerink Partners is acting as exclusive financial advisor and Goodwin Procter LLP is acting as legal counsel to Theseus. Gibson, Dunn & Crutcher LLP is acting as legal counsel to Concentra.