On January 30, 2023 Amplia Therapeutics Limited (ASX: ATX), ("Amplia" or the "Company"), a company developing new drug candidates for the treatment for cancer and fibrosis, reported further progress across its small molecule, focal adhesion kinase (FAK) inhibitor program and the release of its Appendix 4C Cash Flow Report (attached) for the quarter ending 31 December 2022 (Press release, Amplia Therapeutics, JAN 30, 2023, View Source [SID1234626628]).

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Key Highlights from the Quarter

• Completion of recruitment of first cohort of patients into ACCENT Phase 2 clinical trial of AMP945 in pancreatic cancer;
• Encouraging data for AMP886 in a preclinical model of Acute Myeloid Leukemia (AML);
• Dr Christopher Burns appointed as CEO.

Operations Update
Clinical Development
During the Quarter, Amplia announced completion of enrolment of the first cohort of patients in the Company’s Phase 1b/2a ACCENT clinical trial of focal adhesion kinase inhibitor AMP945. The trial tests whether AMP945 enhances the efficacy of gemcitabine/nab-paclitaxel standard-of-care chemotherapy in frontline patients with advanced pancreatic cancer.

By the end of 2022, seven sites in Melbourne, Sydney and Brisbane had been opened to recruit patients into the ACCENT trial. To help raise the profile of the trial amongst pancreatic cancer specialists and oncologists, the company sponsored and attended the Australasian Gastro-Intestinal Trials Group (AGITG) Annual Scientific Meeting in Melbourne in November.

Non-clinical Development

Studies completed during the Quarter also showed that AMP886, Amplia’s second FAK inhibitor, may have utility in the treatment of acute myeloid leukemia (AML). In addition to inhibiting FAK, AMP886 also potently blocks activity of the two related kinases FLT3 and VEGFR3. The company has now shown that AMP886 inhibits AML in an industry-standard MV4-11 disease model carrying a common mutation in FLT3. Patients whose disease carries this mutation often have more rapid progression and significantly worse prognosis. Furthermore, in this model AMP886 enhances the efficacy of venetoclax, a drug approved to treat AML as part of combination therapy. Additional studies exploring the potential of AMP886 in AML and other cancers are underway.

Management

Dr Christopher Burns was appointed as CEO and Managing Director of Amplia Therapeutics on 5th December. Dr Burns was a founder of Amplia Therapeutics and has been a Board member since May 2018.

Financial update

Amplia finished the December 2022 quarter with cash of $10.6 million (September 2022: $11.7 million). During the quarter, the Company had net cash outflows of $1.1 million in relation to operating activities (September 2022: $1.1 million).
Operating cashflows included outflows and inflows of:
• $0.7 million for staff and administration/corporate costs; and
• $0.5 million for research and development costs, which primarily related to Contract Research Organisation (CRO), manufacturing and other CMC related costs incurred in relation to the first stage of the Phase 2 clinical trial for AMP945. Research and development expenditure is forecast to increase in the coming quarters in line with the progression of Phase 1b/2a of the ACCENT clinical trial for AMP945.

Payments to Related Entities

In accordance with Listing Rule 4.7C, payments made to related parties and their associates included in item 6.1 of the Appendix 4C incorporates directors’ fees, salaries and superannuation. Total payments made for the quarter equals $172,929 and relate to payments to the CEO/Managing Director’s in line with employment contracts and payments to the Non-Executive Directors. Outlook and future activities In the coming quarter, the Company expects to report further progress in the ACCENT trial including updates on progression towards optimal dose selection. Work on a regulatory submission to South Korea is well advanced which, if approved, will allow sites to be opened that should further enhance recruitment rate.

Studies continue on the novel metabolite of AMP945 identified in samples from the Phase 1 clinical trial. The presence of the metabolite is not anticipated to impact timelines for the pancreatic cancer trial currently underway.

Non-clinical studies of Amplia’s second FAK inhibitor, AMP886, are ongoing to identify the best clinical opportunities for this compound. Additional non-clinical studies with AMP945 are also underway to explore and support clinical application of the drug in other oncology and non-oncology indications. Data generated from these studies will be communicated as they are received.

This ASX announcement was approved and authorised for release by the Board of Amplia Therapeutics.

On January 29, 2023 ImmuneOnco Biopharmaceuticals (Shanghai) Inc. (hereinafter referred to as "ImmuneOnco") reported that the phase Ib/IIa clinical study of the company’s self-developed bispecific antibody-receptor recombination targeting both CD47 and CD20 protein drug (Project No.: IMM0306), combined with lenalidomide in the treatment of relapsed/refractory CD20-positive B-cell non-Hodgkin’s lymphoma (B-NHL) was approved by the National Medical Products Administration (NMPA) License, this is another new breakthrough of ImmuneOnco in the combination of innovative antibody drugs for the treatment of refractory tumors (Press release, ImmuneOnco Biopharma, JAN 29, 2023, View Source [SID1234655680]).

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Previously, IMM0306 has been approved by China’s NMPA and the U.S. FDA to carry out clinical trials, and has obtained patent authorizations in China, the U.S. and Japan, which consolidates ImmuneOnco’s leading position in the development of CD47-targeted drugs and bispecific antibody research.

Dr. Tian Wenzhi, Founder and Chairman of ImmuneOnco, said, "I am very pleased to see that our Phase Ib/IIa clinical study of IMM0306 combined with lenalidomide (Len) in the treatment of relapsed/refractory CD20-positive B-cell non-Hodgkin’s lymphoma has been approved by the NMPA. IMM0306 is a drug that simultaneously targets CD47. The antibody-receptor recombinant protein (mAb-Trap) of CD20 and CD20 is the world’s first CD47xCD20 dual-target specific molecule that has entered the clinical trial stage. IMM0306 does not bind to human red blood cells in vitro, and preclinical in vivo efficacy tests have shown that its drug effect is significantly better than that of rituximab. The preliminary data of Phase I clinical trials show that the single drug has good safety and good clinical efficacy response, especially in relapsed and refractory follicular lymphoma. Encouraging tumor remission efficacy. The IMM0306 approved today combined with Len has shown a good synergy in the preclinical pharmacodynamic model (below). Therefore, in our development strategy, we will enter the front-line from the indolent lymphoma in the back-line indications, and will be further expanded to more aggressive diffuse large B lymphoma (DLBCL), which is expected to benefit more lymphoma patients."

On January 29, 2021 Amgen reported that its investigational KRASG12C inhibitor sotorasib was granted Breakthrough Therapy Designation (BTD) by the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) (Press release, Amgen, JAN 29, 2023, View Source [SID1234633506]). The designation is for the treatment of patients with KRAS G12C-mutated locally advanced or metastatic non-small cell lung cancer (NSCLC) who have received at least one prior systemic therapy. This is the first BTD submission for Amgen in China, as well as the first under Amgen’s strategic collaboration with BeiGene.

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NSCLC is the most common form of lung cancer, accounting for approximately 80-85% of all cases worldwide.1 KRAS G12C is the most common KRAS mutation in NSCLC.2,3 The mutation is a biomarker of poor prognosis in Chinese NSCLC patients, which may be improved by G12C-specific inhibitors.4 Research has shown that about 3-5% have the KRAS G12C mutation – found most commonly in smokers.4,5

"Given that Breakthrough Therapy Designation is a new pathway in China, we are pleased to receive this designation for sotorasib," said David M. Reese, M.D., executive vice president of Research and Development at Amgen. "This designation underscores the importance of sotorasib and we look forward to working with regulatory authorities in China to bring the first potential targeted therapy to NSCLC patients with the KRAS G12C mutation."

The Breakthrough Therapy Designation is supported by the positive CodeBreaK 100 Phase 2 results in patients with advanced NSCLC whose cancer had progressed despite prior treatment with chemotherapy and/or immunotherapy. In the study, treatment with sotorasib demonstrated durable anticancer activity with a positive benefit-risk profile.6 These results will be presented at the International Association for the Study of Lung Cancer (IASLC) 2020 World Conference on Lung Cancer (WCLC) Presidential Symposium from 3:50-4 p.m. PST on Friday, Jan. 29.

The NMPA’s BTD process is designed to expedite the development and review of therapies that are intended for the prevention or treatment of serious life-threatening diseases for which there is no existing treatment and where preliminary evidence indicates advantages of the therapy over available treatment options.7 This designation shows the potential for sotorasib to become the first targeted treatment available in China for KRAS G12C-mutated NSCLC.

Amgen has taken on one of the toughest challenges of the last 40 years in cancer research by developing sotorasib, the first KRASG12C inhibitor to enter the clinic.8 Sotorasib is being studied in the broadest clinical program exploring 10 combinations with global sites spanning across four continents. In just over two years, the sotorasib clinical trial program has also established the deepest clinical data set with nearly 700 patients studied across 13 tumor types.

About CodeBreaK
The CodeBreaK clinical development program for Amgen’s investigational drug sotorasib is designed to treat patients with an advanced solid tumor with the KRAS G12C mutation and address the longstanding unmet medical need for these cancers. As the most advanced KRAS G12C clinical development program, CodeBreaK has enrolled nearly 700 patients across 13 tumor types since its inception.

CodeBreaK 100, the Phase 1 and 2, first-in-human, open-label multicenter study, enrolled patients with KRAS G12C-mutant solid tumors. Eligible patients must have received a prior line of systemic anticancer therapy, consistent with their tumor type and stage of disease. The primary endpoint for the Phase 2 study was centrally assessed objective response rate. The Phase 2 trial in NSCLC enrolled 126 patients, 124 of whom had centrally evaluable lesions by RECIST at baseline. The Phase 2 trial in colorectal cancer is fully enrolled and topline results are expected in 2021.

A global Phase 3 randomized active-controlled study comparing sotorasib to docetaxel in patients with KRAS G12C-mutated NSCLC (CodeBreaK 200) is currently recruiting. Amgen also has more than 10 Phase 1b combination studies across various advanced solid tumors (CodeBreaK 101) open for enrollment.

For information, please visit www.codebreaktrials.com.

On January 29, 2023 Alpha Biopharma, a developer of innovative drugs, reported that the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) has accepted its New Drug Application (NDA) for Zorifertinib, a next-generation EGFR-TKI specially designed to treat advanced EGFR-mutated non-small cell lung cancer (NSCLC) patients with central nervous system (CNS) metastases (Press release, Alpha Biopharma, JAN 29, 2023, View Source [SID1234626630]). Zorifertinib is the first EGFR-TKI to be tested in a prospective, controlled registration clinical study for this difficult-to-treat patient population, and if approved, it will bring a much-needed new treatment option for these patients.

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Data released by the International Agency for Research on Cancer (IARC) of the World Health Organization (SHO) showed that there were 9.96 million cancer deaths worldwide in 2020, and 1.8 million deaths were from lung cancers, making it the most common cause of cancer deaths. Due to the low CNS penetration rate of most current lung cancer drugs, lung cancers metastasized to the CNS were poorly controlled and have become one of the leading causes of NSCLC patient deaths.

Zorifertinib is a next-generation EGFR-TKI targeting sensitive EGFR mutations (exon 19 deletion and exon 21 L858R) designed for complete blood-brain barrier (BBB) permeability. In addition, Zorifertinib is not a substrate for the efflux transporters P-gp and BCRP, which allows it to achieve and maintain effective drug exposure in the brain tissues and the cerebrospinal fluid.

The EVEREST study was a multinational, multicenter, randomized, open-label, controlled phase II/III clinical trial designed to evaluate the efficacy and safety of Zorifertinib as a first-line treatment for advanced EGFR-mutated NSCLC patients with CNS metastases. The study was carried out in 55 study sites located in the Chinese mainland, Taiwan, South Korea, and Singapore, with a total enrollment of 492 patients. The last patient last visit (LPLV) of the EVEREST study was completed in the third quarter of 2022. Results from the EVEREST study demonstrated that Zorifertinib effectively reduced the risk of disease progression and patient deaths in the target patient population and showed significant efficacy in treating metastatic lesions in the CNS. In addition, Zorifertinib’s safety profile is comparable to other approved EGFR-TKI’s. The primary resistance mutation at the time of disease progression is the EGFR T790M mutation.

Professor Yilong Wu, President of the Chinese Thoracic Oncology Group (CTONG) and the leading principal investigator (PI) of the EVEREST study, said, "Clinical results from this high-quality, controlled study demonstrated that Zorifertinib provided consistent and statistically significant benefits to EGFR-mutated NSCLC patients with different levels of CNS metastasis. It could provide a much-needed new treatment option for these difficult-to-treat patients. The development of Zorifertinib represents a great example of a patient-centric, targeted precision approach to address unmet medical needs.

Eric Zhang, CEO of Alpha Biopharma, said, "after many years of dedicated research and development, we are very pleased to witness that all pre-clinical and clinical data have demonstrated that Zorifertinib can achieve and maintain high CNS exposures, that it is safe, and it is advantageous in controlling CNS and overall disease progression in this difficult-to-treat population. We look forward to working closely with the regulatory agencies around the world to bring this innovative treatment option to patients in dire need.

About Zorifertinib

Zorifertinib is a potent, oral, reversible inhibitor of mutated EGFR (Exon19Del and Exon21L858R). EGFR is widely expressed in human epidermal and stromal cells and is highly expressed in various human malignancies, such as NSCLC. EGFR gene mutation will cause excessive epidermal growth factor receptors on the cell membrane surface, accelerate the abnormal growth and division of cells, and eventually lead to tumorigenesis. CNS metastases are common in EGFR-mutated NSCLC patients and are accompanied by a poor prognosis of earlier disease progression, shorter survival, and lower quality of life. The BBB significantly increases the difficulty of drug penetration into the CNS, which allows the CNS to be a refuge for lung cancer cells. Zorifertinib is a next-generation EGFR-TKI with full blood-brain barrier penetration targeting advanced NSCLC patients with CNS metastases and EGFR-sensitizing mutations. Zorifertinib is currently under NDA submission and has global patent protection.

On January 27, 2023 Marengo Therapeutics, Inc., a company pioneering novel therapeutics targeting the T cell receptor (TCR) Vβ to selectively activate the right T cell subsets to fight cancer, reported that the first patient has been dosed in its ongoing clinical trial of STAR0602 (START-001) (Press release, Marengo Therapeutics, JAN 27, 2023, View Source [SID1234626625]). Marengo’s START-001 trial is a seamless Phase 1/2 clinical trial evaluating the safety and clinical activity of STAR0602 as monotherapy in a biomarker-enriched cohort of patients with PD-1 refractory advanced solid tumors.

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The START-001 trial (NCT05592626) is currently enrolling patients at two top US cancer research institutes, National Institutes of Health (NIH)’s National Cancer Institute (NCI) and Mass General Hospital (MGH)/Harvard Medical School, co-led by seasoned clinical and translational researchers James Gulley, M.D., Ph.D., of NCI and Ryan Sullivan, M.D., of MGH. Additional top cancer centers are planned to join these clinical sites to support the further expansion of the study.

"The Center for Cancer Research’s Center for Immuno-Oncology at the NCI was recently established to explore fundamental questions of cancer immunotherapy through rigorous preclinical studies and translate these findings into clinical trials with the goal of developing novel therapies for a spectrum of cancers with high unmet medical needs. We look forward to studying this novel TCR agonist that selectively activates a subset of αβ T cells in cancer patients at the NCI," said Dr. Gulley, Co-Director of the Center for Immuno-Oncology (CIO), Deputy Director of the Center for Cancer Research (CCR) at the NCI, and acting Clinical Director, NCI.

"The initiation of our first clinical trial with STAR0602 is an important milestone for Marengo and our selective T cell-targeted STAR platform," said Zhen Su, M.D., MBA, Chief Executive Officer of Marengo. "The START-001 trial leverages a deep biology-driven study design to address high unmet clinical needs in patients for whom PD-1 therapies are no longer effective. Our clinical development approach utilizes a biomarker-enriched, tumor-agnostic strategy that offers a much-needed novel approach to cancer drug development. We are confident that evaluating STAR0602 in well-defined populations will allow us to efficiently investigate biological and clinical activity, paving the way for further investigation."

"Cancer immunotherapy has transformed standard of care across many tumor settings and has significantly improved overall survival for patients with cancer. Despite these innovative therapies, most patients progress following treatment creating an urgent need to develop the next wave of novel therapeutics," said Dr. Sullivan, Associate Director, Melanoma Program, MGH Cancer Center. "We are excited to test this novel biology via reinvigorating the T cell compartment in tumors to promote an antitumor immune response distinct from the PD-1 mechanism."