On April 14, 2021 Castle Biosciences, Inc. (Nasdaq: CSTL), a skin cancer diagnostics company providing personalized genomic information to improve cancer treatment decisions, reported data from an independent, prospective study published in the American Journal of Surgery demonstrating DecisionDx-Melanoma’s utility for prediction of outcomes in patients with cutaneous melanoma (Press release, Castle Biosciences, APR 14, 2021, View Source [SID1234578049]). DecisionDx-Melanoma is Castle’s gene expression profile test that uses an individual patient’s tumor biology to predict risk of cutaneous melanoma metastasis or recurrence, as well as sentinel lymph node positivity, independent of traditional staging factors.

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The publication, titled "Utility of a 31-gene expression profile for predicting outcomes in patients with primary cutaneous melanoma referred for sentinel node biopsy," describes a study comparing tumor features, sentinel node biopsy (SLNB) results, and patient outcomes from a prospective database of 383 patients with cutaneous melanoma who both underwent SLNB and had their primary tumor assayed with DecisionDx-Melanoma. Groups were compared by univariate and multivariate analyses, and relapse-free and distant metastasis-free survival (RFS, DMFS) were estimated by Kaplan-Meier method.

The study’s results demonstrated that a Class 2 (high-risk) DecisionDx-Melanoma result was significantly associated with higher rates of SLNB positivity compared to Class 1 (low risk). With respect to risk prognoses, patients who received a Class 2B DecisionDx-Melanoma result and were SLNB-positive experienced the highest recurrence rates (38%), compared to only a 2% recurrence rate for patients who were Class 1A and SLNB-negative. DecisionDx-Melanoma Class 2 results were significantly associated with poorer RFS and DMFS rates compared to Class 1 results, both in the entire cohort of 383 cases and in patients staged as "low risk" (IA-IIA) according to American Joint Committee on Cancer (AJCC) staging criteria.

"We sought to study the utility of this 31 gene expression profile (31-GEP) test in the largest, independent, prospective study to date," said corresponding author John T. Vetto, M.D., FACS, Professor of Surgery, Division of Surgical Oncology, Oregon Health & Science University, Portland. "Current staging parameters in melanoma are invaluable but also imperfect. We were encouraged to find that, like AJCC stage, the 31-GEP results were independently associated with patient outcomes, including recurrence and distant metastasis, and that the 31-GEP results added prognostic information when incorporated with existing features to evaluate patient risk."

About DecisionDx-Melanoma

DecisionDx-Melanoma is a gene expression profile test that uses an individual patient’s tumor biology to predict individual risk of cutaneous melanoma metastasis or recurrence, as well as sentinel lymph node positivity, independent of traditional staging factors, and has been studied in more than 5,700 patient samples. Using tissue from the primary melanoma, the test measures the expression of 31 genes. The test has been validated in four archival risk of recurrence studies of 901 patients and six prospective risk of recurrence studies including more than 1,600 patients. To predict likelihood of sentinel lymph node positivity, the Company utilizes its proprietary algorithm, i31-GEP, to produce an integrated test result. i31-GEP is an artificial intelligence-based neural network algorithm (independently validated in a cohort of 1,674 prospective, consecutively tested patients with T1-T4 cutaneous melanoma) that integrates the DecisionDx-Melanoma test result with the patient’s traditional clinicopathologic features. Impact on patient management plans for one of every two patients tested has been demonstrated in four multicenter and single-center studies including more than 560 patients. The consistent performance and accuracy demonstrated in these studies provides confidence in disease management plans that incorporate DecisionDx-Melanoma test results. Through December 31, 2020, DecisionDx-Melanoma has been ordered more than 68,920 times for use in patients with cutaneous melanoma.

On April 14, 2021 Samsung Biologics reported on the 17th that it has signed a consignment development (CDO) contract with Panolos Biosciences for ‘PB101’, a new anti-cancer drug candidate (Press release, Panolos Bioscience, APR 14, 2021, View Source [SID1234633685]).

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Through this contract, Samsung Biologics plans to provide services throughout the CDO process, from cell line development of Panolos ‘PB101’ to process development, clinical sample production and clinical trial plan (IND) submission support, and non-clinical and global clinical material production.

‘PB101′, Panolos’ next-generation anti-cancer drug candidate, targets all families (VEGF-A, VEGF-B, Placental Growth Factor) of VEGF (Vascular Endothelial Growth Factor) that is overexpressed around cancer cells. It acts to inhibit the growth of cancer cells. ‘PB101’ is a substance with high difficulty in research due to its complex protein structure.

Samsung Biologics established a customized development strategy for the success of ‘PB101’ and was once again recognized for its complex protein-based high-level development capability and differentiated expertise.

Lim Hye-seong, CEO of Panolos, said, "’PB101′ is expected to have excellent efficacy as an anticancer and VEGF-related disease treatment by itself, and moreover, the material itself has already proven its value as a platform technology." He continued, "In the future, in the development of multiple target candidates including ‘PB101’, we expect to be able to demonstrate high synergy through close mutual cooperation with Samsung Biologics, which has development capabilities."

Taehan Kim, CEO of Samsung Biologics, said, "We are very pleased to have entered into a partnership with Panolos, which has outstanding potential in the field of protein new drug development. We will do our best to accelerate the development of our client’s materials with the world’s best CDO service provided by our company"

On April 14, 2021 Hutchison China MediTech Limited ("HUTCHMED") (Nasdaq/AIM: HCM) reported that it was notified that CK Hutchison Holdings Limited ("CK Hutchison") shareholding[1] in HUTCHMED remains unchanged, at 332,478,770 ordinary shares of par value US$0.10 each in the capital of HUTCHMED ("Shares") (Press release, Hutchison China MediTech, APR 14, 2021, View Source [SID1234578012]).

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Each American Depositary Share ("ADS") represents five Shares. As announced on April 8, 2021, HUTCHMED issued a total of 16,393,445 Shares (equivalent to 3,278,689 ADSs) to funds affiliated with Baring Private Equity Asia. HUTCHMED was notified on April 14, 2021 that this issuance diluted CK Hutchison’s holding[1] to 44.66 per cent of the total number of voting rights of HUTCHMED. The date on which the notification threshold was crossed was April 14, 2021.

[1] Held through CK Hutchison’s indirect wholly-owned subsidiary Hutchison Healthcare Holdings Limited.

On April 14, 2021 BioAge Labs, Inc. a biotechnology company developing medications that target the molecular causes of aging to extend healthy human life, reported that it has entered into an exclusive worldwide license agreement with Amgen, Inc. [Head Office: Thousand Oaks; CEO: Robert Bradway] to develop and commercialize Amgen’s clinical-stage APJ agonist, BGE-105 (named AMG 986 by Amgen) to ameliorate muscle aging (Press release, BioAge Labs, APR 14, 2021, View Source [SID1234578031]). In older people, muscle aging causes loss of strength, mobility, and function, driving mortality and multiple age-related diseases and decreasing overall quality of life.

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APJ and its natural agonist apelin are components of a signaling pathway that regulates multiple aspects of muscle metabolism, growth, and repair.

BGE-105 is a potent APJ agonist that can be administered orally or intravenously. Phase 1 clinical trials completed in 2019 in 198 subjects who received the drug for up to 21 days showed that BGE-105 had a tolerable safety profile, with acceptable pharmacokinetics (PK) supporting once-daily administration. BioAge’s first clinical trial of BGE-105, planned for initiation in the first quarter of 2022 under the existing IND, will be a Phase 1 study comparing the pharmacodynamic (PD) effects of BGE-105 in humans with those seen in previous trials examining the effects of the apelin peptide.

"BioAge’s advanced proprietary platform comprehensively analyzes longitudinal human data to identify key molecular drivers of aging, which we then validate in preclinical experiments," said Kristen Fortney, PhD, BioAge’s Chief Executive Officer. "Using this robust approach, we found that higher levels of apelin signalling in older people are associated with increased lifespan and reduced symptoms of frailty. Our human-first analysis suggests that the apelin-mimicking drug BGE-105 could recapitulate these positive effects in older patients."

In mice, deficiency in apelin or APJ accelerates loss of muscle function. Consistent with the key roles of apelin–APJ signaling in muscle physiology, BioAge showed in preclinical experiments that BGE-105 increases running wheel activity and other measures of frailty, improves regeneration, and decreases muscle atrophy due to immobilization in old mice.

"Maintaining muscle mass and strength is key to maintaining physical function in the elderly," said Dr. Cedric Dray, an Associate Professor and BioAge collaborator. In 2018, Dr. Dray’s research group discovered that apelin reverses age-associated sarcopenia, and since then has collaborated with BioAge to evaluate BGE-105 in murine models of muscle regeneration. "It is tremendously exciting to trial in humans an oral APJ agonist that recapitulates the positive effects of apelin peptide."

"As with all of BioAge’s clinical assets, BGE-105 is de-risked in two key ways," Fortney said. "First, data from a previous clinical trial show that the molecule was well tolerated in human patients. Second, our human-centric approach reveals that the drug target is physiologically relevant to human aging — in this case, showing that enhancing apelin signaling is compatible with a long and healthy lifespan. This approach maximizes our potential for success and our ability to efficiently deliver solutions to patients for broader, more impactful outcomes."

Under the terms of the license agreement, which covers all indications, BioAge will make an upfront payment to Amgen, who is entitled to receive development and regulatory milestone payments plus royalties based on annual net sales. Amgen will also receive BioAge shares. BioAge will be responsible for all development, manufacturing, and commercialization of BGE-105 worldwide.

"Because it targets a fundamental mechanism of muscle aging, BGE-105 could be used to treat multiple acute and chronic indications, potentially improving muscle strength in frail elderly people, shortening rehabilitation time after hip fracture, or increasing mobility after extended bed rest," Fortney said. "The licensing agreement represents a major milestone toward our vision of developing a pipeline of treatments that separate growing older from disability and disease, dramatically improving the quality of life as we age."

On April 14, 2021 NOXXON Pharma N.V. (Euronext Growth Paris: ALNOX) (Paris:ALNOX), a biotechnology company focused on improving cancer treatments by targeting the tumor microenvironment (TME), reported the completion of patient recruitment in its Phase 1/2 brain cancer study with lead candidate, NOX-A12 plus radiotherapy (Press release, NOXXON, APR 14, 2021, View Source [SID1234578050]). All three patients participating in the third and final dose cohort have been successfully enrolled and received initial treatment. NOXXON’s Phase 1/2 clinical study is investigating three dose regimens of CXCL12 inhibitor, NOX-A12 (200, 400 and 600 mg/week), each combined with external beam radiotherapy in newly diagnosed brain cancer patients.

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Once the last patient in the third cohort completes four weeks of therapy with NOX-A12 combined with radiotherapy, the independent Data Safety Monitoring Board (DSMB) will convene to assess the safety and tolerability of 600 mg NOX-A12 per week, the highest dose planned in the study. As outlined in the approved study protocol, it is planned for each patient to be treated with NOX-A12 for up to six months. Top-line data from this arm is planned to be available in November 2021.

"The combination of NOX-A12 and radiotherapy has been well tolerated by the participating patients so far. In the upcoming and final planned DSMB meeting, the safety of the highest dose tested will be assessed. Once patients have received treatment over a longer time period, the clinical investigators will analyze all available trial data to define the recommended dose for a Phase 2 glioblastoma study," said Prof. Frank Giordano, Director and Chair of the Department of Radiation Oncology at the University Hospital Bonn.

"Completing patient recruitment for this dose escalation study is an important step in the continued clinical assessment of our novel therapy for patients with difficult-to-treat and highly aggressive brain cancer. We are currently preparing the submission of a protocol amendment to allow the inclusion of additional patients with the goal of expanding the data base for the recommended Phase 2 dose. In addition, our expansion aims to create a basis for enrolling a broader group of patients in future studies, in particular brain cancer patients who would also receive chemotherapy in addition to NOX-A12. Notably, this would allow NOX-A12 to be tested in all first line glioblastoma patients," commented Aram Mangasarian, CEO of NOXXON.