On April 21, 2023 Fosun reported that according to the public announcement made by the Centre for Drug Evaluation of National Medical Products Administration (the "NMPA"), the FCN-159 tablets (the "Investigational New Drug") of Shanghai Fosun Pharmaceutical Industrial Development Company Limited (the "Company" and, together with its subsidiaries/units, the "Group", the same applies below), have been granted breakthrough therapy designation for the treatment of histiocytic tumors (Filing, Fosun, APR 21, 2023, View Source [SID1234633490]).

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II. Basic Information and Research Progress of the Investigational New Drug
The Investigational New Drug is an innovative small molecule chemical drug self-developed by the Group , which is a MEK1/2 selective inhibitor and is intended to be used primarily for the treatment of advanced solid tumors, type I neurofibromas, histiocytic tumors and arteriovenous malformations

As at the date of this announcement, the Investigational New Drug is at the stage of Phase I clinical trial in China (excluding Hong Kong, Macau and Taiwan region for the purpose of this announcement, the same applies below) for the treatment of malignant melanoma; the Investigational New Drug is at the stage of Phase II clinical trials in China, the United States and Europe for the treatment of type I neurofibroma; and the Investigational New Drug is at the stage of Phase II clinical trials in China for the treatment of histiocytic tumors, low-grade glioma and arteriovenous malformations respectively. The application for Phase II clinical trial of the Investigational New Drug for childhood Langerhans cell histiocytosis/Langerhans cell histiocytic hyperplasia has also been approved by the NMPA.

As at the date of this announcement, the MEK1/2 selective inhibitor approved for launch in China include MEGININE (邁吉寧 ) (Trametinib Tablets) of Novartis Europharm Limited. According to the data from IQVIA CHPA (provided by IQVIA, a professional information and strategic consulting service provider for the pharmaceutical and health industry, IQVIA CHPA data represents the drug sales market of hospitals with over 100 beds in China. The actual sales of different drugs may differ from the IQVIA CHPA data to varying degrees due to their different sales distribution channels), the sales of MEK1/2 selective inhibitor in China amounted to approximately RMB98.68 million in 2022. As of March 2023, the Group has invested approximately RMB 311.95 million (unaudited) in total in the research and development ("R&D") of the Investigational New Drug at this stage.

III. Risk Reminder
As required by the relevant laws and regulations in China, the Investigational New Drug is subject to undergo a series of clinical studies and approval by the relevant national drug review department in China before it can be launched. There are certain risks in the R&D of new drugs based on our experience. For example, clinical trials may be terminated due to issues such as safety and/or efficacy.

On April 21, 2023 Nerviano Medical Sciences Srl, a member of NMS Group and a clinical stage company discovering and developing innovative therapies for the treatment of cancer, reported to be included as Plenary Session highlights of the AACR (Free AACR Whitepaper) (American Association for Cancer Research) Annual Meeting 2023 for the data from the First-In-Human study of NMS-03592088 – a novel, potent inhibitor of FLT3, KIT and CSF1R (Press release, Nerviano Medical Sciences, APR 21, 2023, View Source [SID1234630614]). The Phase 1 clinical trial data were presented during an oral scientific session on 16 April.

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NMS-03592088 is an orally available compound that showed superior preclinical activity with respect to first and second generation FLT3 inhibitors and demonstrated a good potency on resistance mutation F691L identified as cause of relapse in patients treated with selective FLT3 inhibitors. NMS-03592088 is currently being explored in MKIA-088-001 trial, a multi-center Phase 1/2 study to evaluate safety, tolerability and efficacy in patients with relapsed or refractory (R/R) acute myeloid leukemia (AML) or chronic myelomonocytic leukemia (CMML).

The Phase 1 portion of the study was a 3+3 design dose escalation with NMS-03592088 administered daily for 21 of 28 days (schedule A) or continuously (schedule B). As of January 26, 44 R/R AML or CMML patients were treated across doses from 20 to 360 mg/day in schedule A or from 120 to 250 mg/day in schedule B. 41 patients had AML and 3 patients had CMML. 24 AML patients were FLT3 positive with FLT3-ITD mutations representing the most common genetic alteration and the majority of them had received at least one prior FLT3 inhibitor (87.5%).

NMS-03592088 showed manageable safety with no maximum tolerated dose characterized. Overall, the most frequent treatment-emergent related adverse events were nausea (any grade, 20.5%), vomiting (13.6%), asthenia (11.4%). A dose-dependent trend of reversible myasthenic syndrome was also characterized.

In terms of clinical benefit, the data showed a dose-dependent trend for response. 5 out of 12 evaluable patients with FLT3 positive AML treated at dose ≥ 300 mg achieved an investigator-assessed response. All these patients had received prior midostaurin and 2 had received prior midostaurin and prior gilteritinib. Two patients with response were able to withdraw from study to receive HSCT. Overall, the duration of response ranged from 1.3-7.9 months.

In summary, NMS-03592088 showed clinical efficacy in patients with FLT3 positive R/R AML, including patients who have failed prior FLT3 inhibitors. These results, together with the manageable safety observed, warrant further development which is now being explored in Phase 2 trial.

"We are pleased to see that NMS-03592088 demonstrates antileukemic activity in FLT3 positive AML patients since these patients are at high risk for poor outcomes" was noted by Lisa Mahnke, MD, PhD, Chief Medical Officer for Nerviano Medical Sciences.

"We believe that despite availability of FLT3 targeted agents there is still need for more effective treatments, including those for patients that have failed current FLT3 inhibitors" according to Hugues Dolgos, PharmD, CEO, Nerviano Medical Sciences.

A copy of today’s presentation "NMS-03592088, a novel, potent FLT3, KIT and CSF1R inhibitor with activity in FLT3 positive acute myeloid leukemia patients with prior FLT3 inhibitor experience" is available at this link: View Source

About Acute Myeloid Leukemia
Acute Myeloid Leukemia (AML) is a rapidly progressing hematologic malignancy that most frequently develops in older adults. FLT3 mutations occur in approximately 30% of AML patients and are associated with aggressive disease, higher relapse rates and worse survival. Despite the approval of FLT3 inhibitors midostaurin and gilteritinib the prognosis of patients with relapsed or refractory disease is poor.

About NMS-03592088
NMS-03592088 is a novel, potent inhibitor of FLT3, KIT and CSF1R, all relevant targets in AML. NMS-03592088 showed superior preclinical activity compared with approved FLT3 inhibitors in different FLT3-driven models. In addition, NMS-03592088 is active on FLT3 gatekeeper mutation F691L causing resistance to first generation FLT3 inhibitors. NMS-03592088 is being developed in AML with two studies currently recruiting (MKIA-088-001 and MKIA-088-002)

Link: AACR (Free AACR Whitepaper)2023_FLT3_ Press release16 April 2023_follow up Plenary Session highlight

On April 21, 2023, HCW Biologics Inc. (the "Company") entered into a secured Development Line of Credit Agreement (the "Agreement") with Prime Capital Ventures, LLC, as lender (the "Lender"), pursuant to which the Lender shall advance loans to the Company in an aggregate principal amount not to exceed $26.25 million (the "Maximum Amount") with a scheduled maturity date of April 20, 2028 (the "Maturity Date") (Filing, HCW Biologics, APR 21, 2023, View Source [SID1234630609]). The note issued pursuant to the Agreement bears interest at a fixed rate of seven (7) percent per annum, due monthly in arrears on the first day of each month, and the outstanding principal on the note shall be due and payable in full on the Maturity Date.

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Under the Agreement, within ten (10) days of receipt of the executed Agreement by each of the Company and the Lender, the Company will be required to wire $5.25 million to Lender to serve as a reserve for the payment of interest under the Agreement. In addition, out of the initial advance, the Company shall pay to the Lender a non-refundable fee in the amount of $1.25 million. The Lender is required to make advances to the Company pursuant to the terms of the Agreement in an amount not to exceed the Maximum Amount. The initial advance from the Lender to the Company is contingent upon the Company’s (1) receipt of all necessary permits and approvals to conduct its business and (2) the compliance with all applicable laws, including zoning and environmental laws.

The Agreement contains customary representations, warranties, affirmative and negative covenants, including financial reporting covenants, events of default and indemnification provisions in favor of the Lender referred to in the Agreement. The covenants include restrictions governing the Company’s ability to amend its certificate of incorporation or bylaws in a manner adverse to the Lender, the Company’s incurrence of liens and indebtedness, the Company’s ability to make investments, and the Company’s entry into certain merger and acquisition transactions or dispositions and other matters, all subject to certain exceptions. In connection with the Agreement, the Lender has been granted a first priority lien and security interest in the Company’s new facility under construction at 3300 Corporate Way, Miramar Florida and various construction project-related bank accounts.

The foregoing description of the Agreement is not intended to be complete and is qualified in its entirety by reference to the Agreement, which is filed as Exhibit 10.1 to this Form 8-K and is incorporated herein by reference.

On April 21, 2023 PharmaEssentia Corporation (TPEx:6446, LuxSE: PHECA, PHECR), a leading fully integrated biopharmaceutical company in Taiwan, reported the closing of its Global Depositary Receipt (GDR) offering of 34,000,000 shares of common stock at US$13.61 per share, generating US$462.7 million (Press release, PharmaEssentia, APR 21, 2023, View Source [SID1234630392]).

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"This marks the largest global health care GDR offering to date in 2023 and reflects confidence in the market opportunity for our approved product and the potential of our pipeline," said Ko-Chung Lin, Ph.D., Founder and Chief Executive Officer, PharmaEssentia.

The 34,000,000 Global Depositary Shares (GDS) represented approximately 10% of total issued and outstanding shares of PharmaEssentia after the offering and were priced at a 5.8% discount to the closing price on the Taipei Exchange (TPEx) of NT$440.5 on April 13, 2023. The GDS were listed on the Luxembourg Stock Exchange (LuxSE) under the ticker symbols PHECA and PHECR.

"PharmaEssentia is pursuing growth in four areas: further penetration of BESREMi (ropeginterferon alfa-2b-njft) in key global markets, including the United States, Japan, South Korea and Europe; geographically expanding BESREMi beyond the countries where it is currently approved; developing additional indications for BESREMi in solid tumors; and advancing a pipeline of new long-acting cytokines, immunotherapy candidates and innovative cell therapies," added Dr. Lin. "This strategy coupled with the company’s strengths in R&D, production, manufacturing, and global commercialization proved attractive to many foreign investors. Demand for PharmaEssentia’s GDS was three times greater than the number of shares offered. The success of our oversubscribed offering will fuel our growth strategy and position us to pursue critical development efforts over the next several years. We believe the strong interest in our offering affirms our strategy and potential."

About BESREMi (ropeginterferon alfa-2b-njft)

BESREMi is an innovative monopegylated, long-acting interferon. With its unique pegylation technology, BESREMi has a long duration of activity in the body and is aimed to be administered once every two weeks (or every four weeks with hematological stability for at least one year), allowing dosing that helps meet the individual needs of patients. BESREMi has orphan drug designation for the treatment of polycythemia vera (PV) in adults in the United States. The product was approved by the European Medicines Agency (EMA) in 2019, in the United States in 2021, and has recently received approval in Japan. The drug candidate was invented by PharmaEssentia and the drug substance is manufactured in the company’s Taichung plant, which was cGMP certified by TFDA in 2017 and by EMA in January 2018. PharmaEssentia retains full global intellectual property rights for the product in all indications. BESREMi was approved with a boxed warning for risk of serious disorders including aggravation of neuropsychiatric, autoimmune, ischemic and infectious disorders.

Please see full Prescribing Information, including Boxed Warning.

On April 21, 2023 Oncoinvent AS, a clinical stage company advancing alpha emitter therapy across a variety of solid cancers, reported the online publication of two articles in the recent special edition of Frontiers in Medicine focused on alpha radioisotopes (Press release, Oncoinvent, APR 21, 2023, View Source [SID1234630391]). The first article, titled "Radiation safety considerations for the use of radium-224-calciumcarbonate-microparticles in patients with peritoneal metastasis," focuses on the effective radiation dose limit for hospital workers, carers, and the public from patients receiving 224Ra-CaCO3-MP. The second, titled "First experience with 224Radium-labeled microparticles (Radspherin) after CRS-HIPEC for peritoneal metastasis in colorectal cancer (a phase 1 study)," supports the favorable safety profile of Radspherin and establishes sustained tolerability in all dose levels for patients treated to date with colorectal cancer.

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"We are excited to share these compelling and important publications in this special edition of Frontiers in Medicine, which continue to demonstrate that all dose levels of Radspherin are well tolerated with no dose limiting toxicities to date," said Jan A. Alfheim, Chief Executive Officer of Oncoinvent. "Additionally, with these publications, we have shown that no precautions related to external exposure should be required for patients treated with 224Ra-CaCO3-MP – a major risk factor to consider in radiopharmaceutical development that has now been significantly reduced. We are highly encouraged by the clinical data we have obtained to date and look forward to leveraging our expertise as a leader within the radiopharmaceutical space and progressing the clinical development of Radspherin."

In the publication titled "Radiation safety considerations for the use of radium-224-calciumcarbonate-microparticles in patients with peritoneal metastasis," six patients with colorectal cancer from the phase 1 trial were injected with 7 MBq of 224Ra-CaCO3-MP. At 3, 24, and 120 hours post injection, the patients underwent measurements with an ionization chamber and a scintillator-based iodide detector as well as whole body gamma camera imaging. Researchers also collected urine and blood samples post injection to estimate activity concentration of 224Ra and 212Pb. It was found that the patients’ median effective whole-body half life of 224Ra-CaCO3-MP ranged from 2.6 to 3.7 days, with a mean value of 3.0 days. Importantly, in the scenarios with exposure at the hospital, sporadic patient contact resulted in a range of 3.9–6.8 μSv per patient, and daily contact resulted in 4.3–31.3 μSv depending on the scenario, suggesting that a single hospital worker can treat around 200-400 patients injected with 224Ra-CaCO3-MP before external exposure is exceeded. Family members and other members of the public were expected to receive well below 0.25 mSv, thereby eliminating the need for restrictions to reduce external exposure. These data demonstrate that, due to low dose rates from the patients and low amount of activity found in blood and urine, no precautions related to external exposure are required when treating patients with Radspherin.

In the publication titled "First experience with 224Radium-labeled microparticles (Radspherin) after CRS-HIPEC for peritoneal metastasis in colorectal cancer (a phase 1 study)," 23 patients were enrolled and administered Radspherin at increasing activity dose levels of 1-2-4-7 over a period of 30 days. A total of 68 grade 2 adverse events were reported for 17 patients during the first 30 days; most were considered related to CRS and/or HIPEC. No DLT was documented at the 7 MBq dose level that was then defined as the recommended dose. Additionally, the biodistribution of Radspherin showed a relatively even peritoneal distribution. These results underscore that all dose levels of Radspherin were well tolerated, and DLT was not reached. Of note, no deaths occurred, and no serious adverse events were considered related to Radspherin. This favorable safety profile in the current study is in line with documentation from other preclinical and clinical studies with other related alpha-emitting compounds administered intraperitoneally.