On March 22, 2024 Alphamab Oncology (stock code: 9966.HK) reported that the phase II clinical research results of anti- PD-L1/CTLA-4 bispecific antibody KN046 plus chemotherapy as first-line treatment for metastatic non-small cell lung cancer (NSCLC) were published online in the renowned journal Cell Reports Medicine (IF: 14.3). Professor Li Zhang from Sun Yat-Sen University Cancer Center is the corresponding author of this paper, and Professor Yuanyuan Zhao is the first author.

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Lung cancer is one of the most common cancers in the world, and it is the malignant tumor with the highest morbidity and mortality in China. According to the latest national cancer statistics released by the National Cancer Center, there are 1.06 million new cases of lung cancer, with a total death toll of 0.73 million in year 2022, far exceeding other tumor types. NSCLC accounts for about 80% – 90% of all lung cancers, and about 57% of NSCLC patients are metastatic at the time of diagnosis. In recent years, immune checkpoint inhibitors have made breakthroughs in the treatment of advanced NSCLC. However, the overall prognosis and long-term therapeutic efficacy still need to be improved.

KN046-202 is a phase II, open-label, multi-center clinical study to evaluate the efficacy, safety and tolerability of KN046 combined with chemotherapy as first-line treatment for metastatic NSCLC. Patients were recruited into two cohorts: patients with non-squamous (non-sq)-NSCLC receive pemetrexed, while those with sq-NSCLC receive paclitaxel, both plus KN046 and carboplatin. Following four cycles (Q3W), maintenance therapy includes KN046 with pemetrexed for non-sq-NSCLC and KN046 for sq-NSCLC. Primary endpoints were confirmed objective response rate (ORR) and duration of response (DoR) as assessed by the investigators according to RECIST version 1.1.

In total, 87 patients were enrolled, including 51 in the non-sq-NSCLC cohort and 36 in the sq-NSCLC cohort. The median age was 61 (range, 32-76) years, and 75.9% were males. As of March 15, 2022, the median follow-up time was 23.1 months.

Efficacy: The confirmed objective response rate (ORR) was 46.0%(95% CI:35.2%-57.0%) and median duration of response (DoR) was 8.1(95% CI:4.14-13.90) months. Median progression-free survival (PFS) was 5.8 (95% CI: 5.26-7.10) months, median overall survival (OS) was 26.6 (95%CI:16.92-NR) months, and the 12-month OS rate was 74.2%(95% CI:63.46%-82.18%). In the non-sq-NSCLC cohort, the confirmed ORR was 43.1%, median DoR was 9.7months, median PFS was 5.8 months, and median OS was 27.2 months; In the sq-NSCLC cohort, the confirmed ORR was 50.0%, median DoR was 7.3months, median PFS was 5.7 months, and median OS was 26.6 months.

Safety: All 87 enrolled patients were evaluable for safety. The most common treatment-related adverse events (TRAEs) were anemia (87.4%), loss of appetite (72.4%), and neutropenia (70.1%). In this study, immune-related adverse event (irAEs), grade ≥3 irAEs, and serious irAEs were reported in 50 (57.5%), 11 (12.6%), and 9(10.3%) patients, respectively. The most common irAEs were pruritus (28.7%), elevated aspartate aminotransferase (24.1%), and rash (21.8%).

In conclusion, the encouraging results from this phase II study showed that KN046 combined with platinum doublet chemotherapy is effective and tolerable as first-line treatment for metastatic NSCLC, which could also be a promising treatment option for this patient population.

About KN046

KN046 is PD-L1/CTLA-4 bispecific antibody independently developed by Alphamab. Its innovative designs include: a novel mechanism – CTLA-4 fused with PD-L1 single domain antibody; engineered to target the tumor microenvironment with high PD-L1 expression, and Treg (suppress tumor immunity) clearing function.

There are about 20 clinical trials of KN046 in different stages covering more than 10 types of tumors including NSCLC, pancreatic cancer, thymic cancer, HCC, ESCC and TNBC in Australia, the US and China. The results of these clinical trials have shown an advantage in survival for patients. Alphamab Oncology has received FDA clearance to enter phase II trial of KN046 based on the clinical results in China and Australia. Moreover, KN046 has obtained the U.S. FDA’s orphan drug designation for thymic epithelial tumor in September 2020. Several pivotal clinical trials are currently being conducted, among which the interim analysis of the phase III clinical study of KN046 combined with chemotherapy as the first-line treatment of NSCLC successfully met the prespecified PFS endpoint.

(Press release, Alphamab, MAR 22, 2024, View Source [SID1234657015])

On March 22, 2024 Ono Pharmaceutical Co., Ltd. (Osaka, Japan; President and CEO: Gyo Sagara; "Ono") reported that it has entered into a comprehensive drug discovery collaboration agreement with the University of Oxford (Oxfordshire, UK; "Oxford") to verify drug discovery seeds and obtain screening compounds for the creation of innovative medicines (Press release, Ono, MAR 22, 2024, View Source [SID1234646257]).

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In this comprehensive collaboration, Ono will select drug discovery seeds from the portfolio of Oxford that align with our research priority themes, and Oxford will conduct validation tests and compound screening for the drug discovery seeds at Oxford. First, Ono has selected the research theme relating to neuroscience, which is one of our four priority research areas and is also an expertise area at Oxford.

 More specifically, Oxford will conduct target validation experiments and compound screening, and Ono will generate drug candidates based on the compounds obtained from Oxford including their hit compounds, towards the development and commercialization of new drug candidates. Ono will obtain an option right to exclusively develop and commercialize these drug candidates worldwide.

 The University of Oxford, located in Oxfordshire, UK, is a collegiate university and one of the top universities in the world. It has the Centre for Medicines Discovery, which is focusing on drug discovery, and based on basic research by experts and researchers with deep insights into drug discovery seeds. It possesses the research infrastructure and drug discovery capabilities that enables to obtain highly unique drug discovery seeds and hit compounds for difficult-to-modulate target groups.

 Ono has generated a number of innovative medicines, by proactively promoting "open innovation", in the fields of cancer, immunology, neurology, and specialty area as priority areas for drug discovery. Ono keeps on committing to creating innovative medicines, aiming to become a global specialty pharma through our unique drug discovery approach based on the open innovation.

 "We are pleased to have the opportunity to collaborate with the University of Oxford, which possesses world-leading research capabilities." said Toichi Takino, Senior Executive Officer / Executive Director, Discovery & Research of Ono. "We expect the potential for the development of new treatment through this partnership."

 "We are delighted to be starting this strategic collaboration with Ono Pharmaceuticals, to validate new therapeutic approaches across a range of different unmet medical needs. " said John Davis, Professor of Pharmaceutical Discovery, Centre for Medicines Discovery, the University of Oxford. "Combining innovative academic research together with the development insights and capability of pharmaceutical industry partners is key to unlocking the potential of new research findings"

On March 22, 2024 Acerand Therapeutics (Acerand) reported the successful completion of the first patient enrollment in the Phase 1/2 clinical trial (ACE-106-001) of their groundbreaking selective PARP1 inhibitor (ACE-86225106 tablets) (Press release, Acerand Therapeutics, MAR 22, 2024, View Source [SID1234641764]).

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ACE-106-001 is a first-in-human trial of Acerand’s self-developed selective PARP1 inhibitor ACE-86225106. This trial consists of two phases: dose escalation and backfill module in phase 1, followed by the dose expansion module in phase 2. The primary objective is to evaluate the safety, tolerability, PK/PD profile, and pre-liminary efficacy of ACE-86225106 as a monotherapy. The coordinating investigators leading this study are Professor Dingwei Ye and Jian Zhang from Fudan University Cancer Hospital. The study is being conducted simultaneously across multiple clinical institutions nationwide.

Remarks by Dr. Genshi Zhao, Acerand Co-Founder, President and CSO:

"This study is the first clinical trial of Acerand and represents a crucial milestone in our journey towards developing innovative small-molecule anti-tumor drug independently. While first-generation pan-PARP inhibitors have been approved for several indications (i.e., advanced ovarian, breast, prostate, and pancreatic cancers), their clinical optimal dose has been limited by adverse effects, limiting the therapeutic window. Highly selective PARP1 inhibitors hold promise in mitigating hematologic toxicity associated with PARP2 inhibition, potentially broaden the therapeutic window, enhancing patient compliance, and demonstrating improved efficacy."

About ACE-86225106：

ACE-86225106 is a novel, oral, and highly selective inhibitor of poly (ADP-ribose) polymerase 1 (PARP1) developed independently by Acerand Therapeutics. It showed significant inhibitory effect on PARP1 in vitro, which was comparable with the positive controls (Olaparib, the first-generation pan-PARPi, and AZD5305, the second-generation PARP1 selective inhibitor under development), and showed no significant inhibitory effect on PARP2/3/5A/5B/6/7/12/14/15. In a DNA-PARP trapping assay, ACE-86225106 showed significant induction of DNA-PARP1 complex trapping, with no significant induction of DNA-PARP2 complex trapping, reaffirming its high PARP1 selectivity. Collectively, these findings suggest that compared to first-generation PARP inhibitors, ACE-86225106 is expected to uphold its anti-tumor efficacy with potentially reduced hematological toxicity risks (i.e. anemia) and extended therapeutic window, thereby improving the prognosis for patients with advanced solid tumor.

On March 22, 2024 Defence Therapeutics Inc. ("Defence" or the "Company"), (CSE: DTC, OTCQB: DTCFF, FSE: DTC), one of the leading Canadian biotechnology companies working in the field of immune-oncology, reported the closing of the 2nd tranche of its previously announced non-brokered private placement (the "Offering") of units of the Company (the "Units") at a price of $1.50 per Unit for aggregate gross proceeds of $600,000.00 (the "Closing") (Press release, Defence Therapeutics, MAR 22, 2024, View Source;utm_medium=rss&utm_campaign=defence-completes-2nd-tranche-of-financing [SID1234641441]). Each Unit consists of one common share in the capital of the Company (each, a "Share") and one common share purchase warrant (each, a "Warrant").

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Each Warrant is exercisable to acquire one Share at an exercise price of $2.00 per Share on or before March 22nd, 2026 (the "Warrant Expiry Date").

In connection with the Closing, the Company paid a cash finder’s fee of $48,000.00 and issued 32,000 finder’s warrants (the "Finder’s Warrants") to a certain qualified arm’s length finder. Each Finder’s Warrant is exercisable into one Share at an exercise price of $2.00 per Share on or before the Warrant Expiry Date.

The Company intends to use the net proceeds of the Offering to advance its preclinical and clinical programs and for general working capital.

All securities issued in connection with the Offering are subject to a statutory hold period of four months plus a day from their date of issue in accordance with applicable securities legislation.

The securities being referred to in this news release have not been, nor will they be, registered under the United States (U.S.) Securities Act of 1933, as amended, and may not be offered or sold in the U.S. or to, or for the account or benefit of, U.S. persons absent registration or an applicable exemption from the registration requirements. This news release does not constitute an offer to sell or the solicitation of an offer to buy nor shall there be any sale of the securities in any jurisdiction in which such offer, solicitation or sale would be unlawful.

On March 22, 2024 Castle Biosciences, Inc. (Nasdaq: CSTL), a company improving health through innovative tests that guide patient care, reported that new data highlighting the performance of its DecisionDx-Melanoma test in predicting risk of sentinel lymph node (SLN) positivity in patients with CM is being presented at the Society of Surgical Oncology 2024 (SSO 2024) Annual Meeting, being held March 20-23 in Atlanta (Press release, Castle Biosciences, MAR 22, 2024, View Source [SID1234641395]).

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"We have previously demonstrated that our DecisionDx-Melanoma test identifies patients who are eligible for an SLNB but have less than a 5% likelihood of being SLN positive, and could therefore consider avoiding the procedure," said Derek Maetzold, president and chief executive officer of Castle Biosciences. "We have also demonstrated that our test is a strong and independent predictor of metastasis. The study that was orally presented at SSO 2024 demonstrates that patients who did avoid an SLNB procedure had excellent outcomes to date. This demonstration is highly important as it showed that our test can help patients avoid an unnecessary procedure."

DecisionDx-Melanoma is supported by 50 peer-reviewed publications involving more than 10,000 patient samples, demonstrating its robust value in guiding risk-aligned patient care. The test has been designed and validated to inform two clinical questions in the management of melanoma: a patient’s risk of melanoma recurrence and metastasis, and their individual risk of SLN positivity, as highlighted in Castle’s SSO 2024 abstracts outlined below.

DecisionDx-Melanoma

Oral Presentation Number and Title: 62: Prospective validation of the i31-gene expression profile test for cutaneous melanoma to select patients who may consider foregoing sentinel lymph node biopsy
Session: Melanoma Parallel Session
Presenter and Lead Author: J. Michael Guenther, M.D., St. Elizabeth Physicians, Edgewood, Kentucky
Summary: This study shares three-year outcomes data from Castle’s prospective, multicenter study of patients with CM who were being considered for an SLNB (n=322). SLNB is an invasive surgical procedure used to determine whether a patient’s cancer has spread to nearby lymph nodes; the procedure returns a surgical result that is negative for metastasis in approximately 88% of patients. Current National Comprehensive Cancer Network guidelines use a 5% likelihood of SLN positivity as the threshold to avoid versus consider/recommend an SLNB due to an increased risk of metastasis. DecisionDx-Melanoma has been validated to provide a patient’s individualized risk of SLN positivity (i31-GEP for SLNB) by integrating clinical and pathologic risk factors with the patient’s tumor biology. In the study, no patients with a DecisionDx-Melanoma predicted risk of SLN positivity less than 5% had a positive SLN (among all tumor stages studied). If DecisionDx-Melanoma was used to inform management decisions, the test’s results could have further reduced the number of patients with T1-T2 tumors who could have avoided SLNB by 25%. Additionally, at three years, all patients with a low-risk DecisionDx-Melanoma test result were recurrence free (recurrence free survival of 100%). These data demonstrate that use of DecisionDx-Melanoma test results can guide accurate, risk-aligned clinical decision-making regarding the SLNB surgical procedure, within current guidelines. Further, the test can identify low-risk patients who can safely consider foregoing SLNB, thereby reducing unnecessary SLNB procedures (by approximately 25% in this study alone) and the associated costs and risks of complications that accompany them.

ePoster Number and Title: E309: Utility of 31-gene expression profile test in identifying patients with T1 cutaneous melanoma at high risk of SLN positivity and recurrence
Session: Melanoma Parallel Session

Summary: In a pooled cohort of 979 patients with thin (T1) tumors, a DecisionDx-Melanoma Class 2B result was the strongest predictor of a positive SLN, among other risk factors that included patient age, tumor location, Breslow thickness, tumor ulceration and more. While the study outlined above demonstrates the ability of the test to identify patients at low risk of SLN positivity who can safely forgo SLNB, this study shows that it can also identify patients at high risk who should consider it. By identifying patients who have a higher risk of SLNB positivity and recurrence, DecisionDx-Melanoma can help determine which patients should be considered for more intensive management, such as SLNB, increased follow-up frequency and imaging surveillance, to improve patient outcomes.

ePosters are available for conference attendees in the ePoster Online Gallery.

About DecisionDx-Melanoma

DecisionDx-Melanoma is a gene expression profile risk stratification test. It is designed to inform two clinical questions in the management of cutaneous melanoma: a patient’s individual risk of sentinel lymph node (SLN) positivity and a patient’s personal risk of melanoma recurrence and/or metastasis. By integrating tumor biology with clinical and pathologic factors using a validated proprietary algorithm, DecisionDx-Melanoma is designed to provide a comprehensive and clinically actionable result to guide risk-aligned patient care. DecisionDx-Melanoma has been shown to be associated with improved patient survival and has been studied in more than 10,000 patient samples. DecisionDx-Melanoma’s clinical value is supported by 50 peer-reviewed and published studies, providing confidence in disease management plans that incorporate the test’s results. Through Dec. 31, 2023, DecisionDx-Melanoma has been ordered more than 150,000 times for patients diagnosed with cutaneous melanoma.