On August 23, 2022 AdvanCell, an Australian radiopharmaceutical company with a platform technology for a revolutionary cancer treatment called Targeted Alpha Therapy, reported the closing of an A$18 million Series B financing round led by Morningside (Press release, Advancell, AUG 23, 2022, View Source [SID1234618578]).

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Andrew Adamovich, CEO and Founder of AdvanCell noted, "We are very pleased with our progress to date and delighted that we will continue our rapid growth with the support of our shareholders. We have had a long-term relationship with our lead investor, Morningside, and are excited to come closer still to our goal to ‘Change the Course of Cancer Treatment.’"

Targeted Alpha Therapies represent the most exciting opportunity to treat currently untreatable cancers. The technology harnesses the natural decay and radiochemical properties of certain elements, in combination with specific targeting molecules, to selectively deliver cell-killing radiation to the tumour cell. AdvanCell believes this precise and powerful treatment will rapidly become a leading pillar of cancer treatment, providing treatments for diseases for which there are currently no effective options. Targeted Alpha Therapies demonstrate incredible efficacy, however widespread adoption and large commercial product launches require a scalable and reliable global isotope supply. AdvanCell was established to solve this problem.

AdvanCell’s ability to produce isotope on-demand and at scale, and its in-house radiopharmaceutical manufacturing expertise positions AdvanCell to play a leading role in this rapidly growing market. With additional support from NSW Health Medical Devices Fund and the Federal government’s Research & Development Tax Incentive, AdvanCell has developed a world-first scalable manufacturing platform to produce alpha-emitting isotopes for research, pre-clinical and clinical use and to advance its own and its partners’ radiopharmaceutical products.

Anthony Aiudi from Morningside commented, "AdvanCell is leveraging its ability to make alpha isotopes at scale and in clinically useful amounts along with its radiochemistry expertise, to develop an exciting portfolio of Targeted Alpha Therapies. Targeted Alpha Therapies hold incredible promise however their development has been hamstrung by a lack of radioisotope supply. Together with the team at AdvanCell, we look forward to writing a new chapter in oncology, to target large patient populations with significant unmet needs."

Mr Aiudi has been appointed to the Board of AdvanCell, joining Mr Adamovich, Bill Ferris AC, co-founder of CPE Capital, Adrian "Adi" Patterson, former Australian Nuclear Science and Technology Organisation (ANSTO) CEO and Kevin Cameron, CEO of Ionetix.

Bill Ferris AC, Chair remarked, "Our executive team has articulated a credible pre-clinical and clinical pathway for the delivery of the Company’s novel Targeted Alpha Therapies. Having successfully developed the manufacturing platform essential for the reliable and scalable supply of isotopes, the Company is on schedule with its pre-clinical work and is now moving into first-in-human trials. AdvanCell is on track to become a leading radiopharmaceutical company with a platform technology enabling novel cancer treatments."

On August 23, 2022 GeneCentric Therapeutics, a company making precision medicine more precise through RNA-based diagnostics, reported its new publication in Cancer Research Communications that compares the immunogenomic response profiles to anti-PD-(L)1 or IL-2 therapy and the development of a novel response classifier to IL-2 treatment1 (Press release, GeneCentric Therapeutics, AUG 23, 2022, View Source [SID1234618577]). Cancer Research Communications is an open access peer-reviewed journal published by the American Association for Cancer Research (AACR) (Free AACR Whitepaper). The study was conducted as a collaboration between Atrium Health Levine Cancer Institute, Sanofi, and GeneCentric and evaluated real-world data from patients diagnosed with renal cell carcinoma (RCC) who were treated with immune-oncology agents. Results suggest that common and distinct immune-related response markers for IL-2 and anti-PD-(L)1 therapy may help guide their use, either alone or in combination.

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"It is exciting to share the initial findings from this important collaboration where we attempted to identify the immunogenomic differences between IL-2 and anti-PD-1 responders in renal cell carcinoma," said Dr. Asim Amin, medical oncologist, Atrium Health Levine Cancer Institute, and study co-principal investigator. "Using RNA expression analysis, we were able to identify key characteristics that are unique to each treatment modality, as well as those that are shared between the two. With this work we were able to develop a novel IL-2 response signature that may have prognostic potential."

A primary focus of the study was to obtain a deeper understanding of the tumor microenvironment similarities and/or differences that may lead to IL-2 or anti-PD-(L)1 therapy response. Retrospective tumor samples and corresponding clinical response data were collected from patients with a primary diagnosis of RCC who were treated with high-dose IL-2 (HD-IL-2; aldesleukin) and compared to existing data from a similar cohort of RCC patients treated with the anti-PD-1 nivolumab2. Tumor samples from HD-IL-2 treated patients underwent RNA sequencing (RNAseq) prior to immunogenomic analysis. As a result, a novel RNA-based IL-2 treatment response signature was discovered that could ultimately assist in further developing diagnostics for next-generation IL-2 agents, several of which are in clinical development.

About Renal Cell Carcinoma

Renal cell carcinoma (RCC) is the most common type of kidney and renal pelvis cancer in adults. In the United States, it is estimated that there will be approximately 79,000 new cases of kidney and renal pelvis cancer in 2022 and almost 14,000 deaths. Kidney and renal pelvis cancer, which includes RCC, is considered the 8th most common type of cancer. Standard treatment options for RCC are surgery, radiation, chemotherapy, targeted therapy or immunotherapy.

On August 23, 2022 NorthStar Medical Radioisotopes, LLC, a global innovator in the development, production and commercialization of radiopharmaceuticals used for therapeutic applications and medical imaging, reported the signing of a long-term supply agreement for the therapeutic radioisotope actinium-225 (Ac-225) with Aktis Oncology, Inc (Press release, NorthStar Medical Radiostopes, AUG 23, 2022, View Source [SID1234618576]). Under terms of the agreement, NorthStar will be a major supplier of high purity non-carrier-added (n.c.a.) Ac-225 to Aktis. Aktis will use NorthStar’s Ac-225 to advance development of its proprietary tumor-targeting agents intended to deliver transformative efficacy for patients with solid tumors.

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Ac-225 is a high energy alpha-emitting radioisotope of increasing interest for clinical studies investigating the use of targeted radiopharmaceutical therapy, which combines select molecules with therapeutic radioisotopes to directly target and deliver therapeutic doses of radiation to destroy cancer cells in patients with serious disease. Ac-225 carries sufficient radiation to cause cell death in a localized area of targeted cells, while its half-life limits unwanted radioactivity in patients. Clinical research and commercial use of Ac-225 have been constrained by chronic short supply due to limitations of current production technology. NorthStar is positioned to be the first commercial-scale producer of Ac-225 for advancing clinical research and commercial radiopharmaceutical therapy products. The Company will use its electron accelerator technology to produce n.c.a. Ac-225 that is free of long-lived radioactive contaminants and byproducts associated with other production methods. Such contaminants pose regulatory and waste management challenges for pharmaceutical companies, hospitals, and health systems.

"We are very pleased to enter this Ac-225 supply agreement with Aktis Oncology, and we look forward to working with them in their efforts to provide targeted alpha radiopharmaceuticals to treat patients with cancer," Stephen Merrick, Chief Executive Officer of NorthStar Medical Radioisotopes. "NorthStar is poised to be the first commercial-scale producer of Ac-225, utilizing our n.c.a. Ac-225 production technology that is environmentally preferable and non-uranium based, utilizing state-of-the-art electron beam accelerator production that provides increased capacity and scheduling flexibility. Construction of our dedicated Actinium-225 Production facility is well underway, with initial production of radiochemical grade Ac-225 planned for late 2023. We expect to submit a Drug Master File to the FDA in 2024, which, upon acceptance, will allow NorthStar to provide cGMP grade Ac-225."

"Aktis Oncology is harnessing the power of targeted alpha radiotherapy to treat a broad range of cancers, including breast, lung, colorectal, bladder, and liver cancers," said Matthew Roden, PhD, Aktis Oncology President and Chief Executive Officer. "Aktis is pleased have NorthStar as an experienced and reliable partner in innovative, accelerator-based radioisotope production technology as our programs advance towards the clinic. We look forward to working with NorthStar to supply Ac-225 to deliver highly transformative treatments for patients with cancer."

On August 23, 2022 Daiichi Sankyo (TSE: 4568) reported that the European Medicines Agency (EMA) has validated the marketing authorization application (MAA) for quizartinib in combination with standard cytarabine and anthracycline induction and standard cytarabine consolidation chemotherapy, and as continuation monotherapy following consolidation, for the treatment of adult patients with newly diagnosed acute myeloid leukemia (AML) that is FMS-like tyrosine kinase 3 internal tandem duplication (FLT3-ITD) positive (Press release, Daiichi Sankyo, AUG 23, 2022, View Source [SID1234618575]).

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AML is one of the most common forms of leukemia in adults, representing about one-third of all cases.1 In Europe, approximately 18,000 people are diagnosed with AML each year and the five-year survival rate is reported at 17% for adult patients.2,3 Of all newly diagnosed cases of AML, approximately 25% carry the FLT3-ITD gene mutation, which is associated with a particularly unfavorable prognosis including increased risk of relapse and shorter overall survival.4

"There is a need to improve survival for the majority of patients with acute myeloid leukemia, particularly those with the FLT3-ITD subtype, which is aggressive and difficult to treat," said Ken Takeshita, MD, Global Head, R&D, Daiichi Sankyo. "We look forward to working with the EMA to support their review of quizartinib as a potential option for patients with newly diagnosed FLT3-ITD positive acute myeloid leukemia."

Validation confirms that the application is complete and commences the scientific review process by the EMA’s Committee for Medicinal Products for Human Use (CHMP). The application is based on data from the QuANTUM-First phase 3 trial recently presented at the European Hematology Association (EHA) (Free EHA Whitepaper) (#EHA2022) Congress. In QuANTUM-First, quizartinib combined with standard cytarabine and anthracycline induction and standard cytarabine consolidation chemotherapy, and continued as monotherapy following consolidation, demonstrated a statistically significant and clinically meaningful improvement in overall survival (OS) in adult patients with newly diagnosed FLT3-ITD positive AML compared to chemotherapy alone. The safety of quizartinib combined with intensive chemotherapy and as continuation monotherapy in QuANTUM-First was generally manageable and consistent with previous clinical trials. The incidence of Grade ≥3 QT prolongation was low, with uncommon ventricular arrythmia events. Overall, the risk of QT prolongation was manageable with ECG monitoring, quizartinib dose modification and correction/elimination of additional risk factors.

About QuANTUM-First

QuANTUM-First is a randomized, double-blind, placebo-controlled global phase 3 study evaluating quizartinib in combination with standard cytarabine and anthracycline induction and standard cytarabine consolidation chemotherapy, and as continuation monotherapy following consolidation, in adult patients aged 18-75 with newly diagnosed FLT3-ITD positive AML. Patients were randomized 1:1 into two treatment groups to receive quizartinib or placebo combined with anthracycline- and cytarabine-based regimens. Eligible patients, including those who underwent hematopoietic stem cell transplant (HSCT), continued with quizartinib or placebo for up to 36 cycles.

The primary study endpoint was OS. Secondary endpoints include event-free survival (EFS), post-induction rates of complete remission (CR) and composite complete remission (CRc), and the percentage of patients who achieve CR or CRc with FLT3-ITD minimal residual disease negativity. Safety and pharmacokinetics, along with exploratory efficacy and biomarker endpoints, also were evaluated. QuANTUM-First enrolled 539 patients at 193 study sites across Asia, Europe, North America, Oceania and South America. For more information, visit Clinicaltrialsregister.eu or ClinicalTrials.gov.

About Acute Myeloid Leukemia (AML)

More than 474,500 new cases of leukemia were reported globally in 2020 with more than 311,500 deaths.5 AML is one of the most common types of leukemia in adults, representing about one-third of all cases, and the average age of diagnosis is 68 years old.1 In Europe, approximately 18,000 people are diagnosed with AML each year and the five-year survival rate is reported at 17% for adult patients.2,3 The conventional treatment for newly diagnosed AML is intensive induction and consolidation chemotherapy with HSCT for eligible patients.6,3

About FLT3-ITD

FLT3 (FMS-like tyrosine kinase 3) is a tyrosine kinase receptor protein normally expressed by hematopoietic stem cells that plays an important role in cell development, promoting cell survival, growth and differentiation through various signaling pathways.4 Mutations of the FLT3 gene, which occur in approximately 30% of AML patients, can drive oncogenic signaling.4 FLT3-ITD (internal tandem duplication) is the most common type of FLT3 mutation in AML, occurring in about 25% of all newly diagnosed patients, and is associated with increased risk of relapse and shorter overall survival.4

About Quizartinib

Quizartinib is an oral, selective type II FLT3 inhibitor currently in clinical development for treatment of FLT3-ITD positive AML. In addition to QuANTUM-First, the quizartinib development program includes a phase 1/2 trial in pediatric and young adult patients with relapsed/refractory FLT3-ITD positive AML in Europe and North America. Several phase 1/2 combination studies with quizartinib are also underway at The University of Texas MD Anderson Cancer Center as part of a strategic research collaboration focused on accelerating development of Daiichi Sankyo pipeline therapies for AML.

Quizartinib, which is currently not approved in Europe, has been granted Orphan Drug Designation for the treatment of AML in Europe, Japan and the U.S. Quizartinib has received Fast Track Designation from the U.S. Food and Drug Administration for the treatment of adult patients with newly diagnosed AML that is FLT3-ITD positive, in combination with standard cytarabine and anthracycline induction and cytarabine consolidation chemotherapy. Quizartinib is currently approved for use in Japan for the treatment of adult patients with relapsed/refractory FLT3-ITD AML, as detected by an approved test. Quizartinib is an investigational medicine in all countries outside of Japan.

On August 23, 2022 Propanc Biopharma, Inc. (OTCQB: PPCB) ("Propanc" or the "Company"), a biopharmaceutical company developing novel cancer treatments for patients suffering from recurring and metastatic cancer, reported that recombinant trypsinogen and chmyotrypsinogen were synthesized via the Proenzyme Optimization Project (POP1) joint research and drug discovery program (Press release, Propanc, AUG 23, 2022, View Source [SID1234618574]). In the case of trypsinogen, the initial success of producing trypsinogen synthetically has now advanced to the stage where optimization of protein production is underway, whereas purification and yield of chymotrypsinogen is currently the focus of research. The program is designed to produce a backup clinical compound to the Company’s lead product candidate, PRP, which is targeting metastatic cancer from solid tumors. According to Emergen Research, the global metastatic cancer market is projected to be worth $111 Billion by 2027.

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A synthetic version of trypsinogen and chymotrypsinogen could have additional benefits to the global healthcare system that could further capitalize on the new therapeutic approach to treating cancer that the Company’s lead product candidate PRP offers cancer sufferers. For example, both proenzymes synthesized by an in vivo (living organism) system to produce crystalized proteins that could be maintained for long periods without suffering degradation, even in the absence of refrigeration. This will be particularly useful for a longer shelf life as well as global distribution of the drug product, particularly in warmer climates and developing regions where refrigeration may not be available. The program’s lead research scientist, Mr. Aitor González is consulting with Professor Diethard Mattanovich, Institute of Microbiology and Microbial Biotechnology, at the University of Natural Resources and Life Sciences, Vienna, Austria, Europe, and is working towards full scale manufacture of a synthetic recombinant formulation to PRP.

"The work undertaken by Aitor in Professor Mattanovich’s laboratory is very careful, detailed work, and it looks like we’re getting close to getting chymotrypsinogen production, as we are already able to produce trypsinogen," said Dr. Julian Kenyon, Propanc’s Chief Scientific Officer. "A fully synthetic recombinant version of PRP would have tremendous implications from a regulatory perspective, but also a practical, commercial benefit for global distribution."

The objective of the POP1 program is to produce large quantities of trypsinogen and chymotrypsinogen for commercial use that exhibits minimal variation between lots and without sourcing the proenzymes from animals. Propanc is undertaking the challenging research project in collaboration with the Universities of Jaén and Granada, led by Mr. González, supported by Prof. Macarena Perán, Ph.D. and Prof. Juan Antonio Marchal M.D., representing the Universities, respectively, and Dr. Kenyon.

PRP is a mixture of two proenzymes, trypsinogen and chymotrypsinogen from bovine pancreas administered by intravenous injection. A synergistic ratio of 1:6 inhibits growth of most tumor cells. Examples include kidney, ovarian, breast, brain, prostate, colorectal, lung, liver, uterine and skin cancers.