On June 30, 2022 AstraZeneca reported that Positive high-level results from a planned interim analysis of the AEGEAN Phase III trial showed treatment with it’s Imfinzi (durvalumab) in combination with neoadjuvant chemotherapy before surgery demonstrated a statistically significant and meaningful improvement in pathologic complete response (pCR) compared to neoadjuvant chemotherapy alone for patients with resectable non-small cell lung cancer (NSCLC) (Press release, AstraZeneca, JUN 30, 2022, View Source [SID1234616401]).

A statistically significant improvement in major pathologic response (MPR) was also observed. The trial will continue as planned to assess the additional primary endpoint of event-free survival (EFS) to which the Company, investigators and participants remain blinded.

The safety and tolerability of adding Imfinzi to neoadjuvant chemotherapy was consistent with the known profile for this combination and did not decrease the number of patients able to undergo successful surgery versus chemotherapy alone.

Up to 30% of all patients globally with NSCLC are diagnosed early enough to have surgery with curative intent.1-3 However, only around 56-65% of patients with Stage II disease will survive for five-years. This decreases to 24-41% for patients with Stage III disease.4

Susan Galbraith, Executive Vice President, Oncology R&D, said: ”Treating resectable lung cancer early provides the best chance for a cure, yet lung cancer will still recur within five years for the majority of patients despite chemotherapy and successful surgery. Engaging the immune response with Imfinzi both before and after surgery is an exciting new strategy, and we hope these early findings from AEGEAN will lead to improved survival for lung cancer patients in this potentially curative setting."

These pCR data will be shared with global health authorities and presented at a forthcoming medical meeting when EFS results are available.

AstraZeneca has several ongoing registrational trials focused on testing Imfinzi in earlier stages of lung cancer, including in resectable NSCLC (ADJUVANT BR.31) and unresectable NSCLC (PACIFIC-2, 4, 5, 8 and 9), and in limited-stage small cell lung cancer (SCLC) (ADRIATIC).

Imfinzi is approved in the curative-intent setting of unresectable Stage III NSCLC in patients whose disease has not progressed after chemoradiotherapy in the US, Japan, China, across the EU and many other countries, and is the global standard of care in this setting based on the PACIFIC Phase III trial. Imfinzi is also approved in the US, EU, Japan, China and many other countries around the world for the treatment of extensive-stage SCLC based on the CASPIAN Phase III trial.

Notes

Lung cancer
In 2020, an estimated 2.2 million people were diagnosed with lung cancer worldwide.5 Lung cancer is the leading cause of cancer mortality among men and women and accounts for about one-fifth of all cancer-related deaths.5 Lung cancer is broadly split into NSCLC and SCLC, with 80-85% classified as NSCLC.6 The majority of NSCLC patients are diagnosed with advanced disease while approximately 25-30% present with resectable disease at diagnosis. 1-2 Early-stage lung cancer diagnoses are often only made when the cancer is found on imaging for an unrelated condition.7-8

For patients with resectable tumours, the majority of patients eventually develop recurrence despite complete tumour resection and adjuvant chemotherapy.

AEGEAN
AEGEAN is a randomised, double-blind, multi-centre, global Phase III trial evaluating Imfinzi as perioperative treatment for patients with resectable Stage IIA-IIIB (tumours greater than or equal to 4cm or node positive) NSCLC with no EGFR or ALK genomic tumour aberrations, irrespective of PD-L1 expression. Perioperative therapy includes treatment before and after surgery, also known as neoadjuvant/adjuvant therapy. In the trial, 802 patients were randomised to receive a 1500mg fixed dose of Imfinzi every three weeks plus chemotherapy or placebo plus chemotherapy for four cycles prior to surgery, followed by Imfinzi or placebo every four weeks (for up to 12 cycles) after surgery.

In the AEGEAN trial, the primary endpoints are pCR, defined as no viable tumour following neoadjuvant therapy, and EFS, defined as the time from randomisation to an event like tumour recurrence or progression. At this interim analysis EFS was not assessed. Key secondary endpoints are MPR, defined as residual viable tumour of less than or equal to ten percent following neoadjuvant therapy, disease-free survival, overall survival, safety and quality of life. The trial is being conducted across 264 centres in more than 25 countries including in the US, Canada, Europe, South America and Asia.

Imfinzi
Imfinzi (durvalumab) is a human monoclonal antibody that binds to the PD-L1 protein and blocks the interaction of PD-L1 with the PD-1 and CD80 proteins, countering the tumour’s immune-evading tactics and releasing the inhibition of immune responses.

As well as global approvals in lung cancer, Imfinzi is approved for previously treated patients with advanced bladder cancer in several countries.

Since the first approval in May 2017, more than 100,000 patients have been treated with Imfinzi.

As part of a broad development programme, Imfinzi is being tested as a single treatment and in combinations with other anti-cancer treatments for patients with SCLC, NSCLC, bladder cancer, several GI cancers, ovarian cancer, endometrial cancer and other solid tumours.

In the past year, Imfinzi combinations have resulted in positive Phase III trials in multiple additional cancer settings including; unresectable advanced liver cancer (HIMALAYA), biliary tract cancer (TOPAZ-1) and metastatic NSCLC (POSEIDON) and the data are under review with global health authorities.

AstraZeneca in lung cancer
AstraZeneca is working to bring patients with lung cancer closer to cure through the detection and treatment of early-stage disease, while also pushing the boundaries of science to improve outcomes in the resistant and advanced settings. By defining new therapeutic targets and investigating innovative approaches, the Company aims to match medicines to the patients who can benefit most.

The Company’s comprehensive portfolio includes leading lung cancer medicines and the next wave of innovations, including Tagrisso (osimertinib) and Iressa (gefitinib); Imfinzi (durvalumab) and tremelimumab; Enhertu (trastuzumab deruxtecan) and datopotamab deruxtecan in collaboration with Daiichi Sankyo; Orpathys (savolitinib) in collaboration with HUTCHMED; as well as a pipeline of potential new medicines and combinations across diverse mechanisms of action.

AstraZeneca is a founding member of the Lung Ambition Alliance, a global coalition working to accelerate innovation and deliver meaningful improvements for people with lung cancer, including and beyond treatment.

AstraZeneca in immunotherapy
Immunotherapy is a therapeutic approach designed to stimulate the body’s immune system to attack tumours. The Company’s Immuno-Oncology (IO) portfolio is anchored in immunotherapies that have been designed to overcome evasion of the anti-tumour immune response. AstraZeneca is invested in using IO approaches that deliver long-term survival for new groups of patients across tumour types.

The Company is pursuing a comprehensive clinical-trial programme that includes Imfinzi as a single treatment and in combination with tremelimumab and other novel antibodies in multiple tumour types, stages of disease, and lines of treatment, and where relevant using the PD-L1 biomarker as a decision-making tool to define the best potential treatment path for a patient.

In addition, the ability to combine the IO portfolio with radiation, chemotherapy, and targeted small molecules from across AstraZeneca’s oncology pipeline, and from research partners, may provide new treatment options across a broad range of tumours.

AstraZeneca in oncology
AstraZeneca is leading a revolution in oncology with the ambition to provide cures for cancer in every form, following the science to understand cancer and all its complexities to discover, develop and deliver life-changing medicines to patients.

The Company’s focus is on some of the most challenging cancers. It is through persistent innovation that AstraZeneca has built one of the most diverse portfolios and pipelines in the industry, with the potential to catalyse changes in the practice of medicine and transform the patient experience.

AstraZeneca has the vision to redefine cancer care and, one day, eliminate cancer as a cause of death.

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On June 30, 2022 Synaffix B.V. (Synaffix), a biotechnology company focused on commercializing its clinical-stage platform technology for the development of antibody-drug conjugates (ADCs) with best-in-class therapeutic index, reported that Kyowa Kirin Co., Ltd. (Kyowa Kirin, TSE:4151), a global specialty pharmaceutical company that strives to create new value through the pursuit of advances in life sciences and technologies, has expanded the license agreement with Synaffix (announced in August 2021) by adding a third ADC target to its research evaluation and development efforts under this deal (Press release, Synaffix, JUN 30, 2022, View Source [SID1234616400]). In addition it exercised its option to take exclusive development and commercialization rights for an undisclosed ADC target under the terms of this agreement.

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This follows a successful initial research collaboration between the companies whereby Kyowa Kirin has demonstrated a highly competitive preclinical therapeutic index for its lead program under this collaboration, prepared from a Kyowa Kirin antibody using Synaffix’s ADC technology.

The technology licensed from Synaffix include GlycoConnect, HydraSpace, and multiple toxSYN linker-payloads, which allow for the drug-to-antibody ratio (DAR) to be tailored to 1, 2 or 4 to optimize the therapeutic index of the ADC.

Under the terms of the amended license agreement, Synaffix will receive an immediate payment of $5 million and is eligible to receive total potential payments for the first ADC program alone of up to $171m plus royalties on commercial sales.

Floris van Delft, Ph.D., Chief Scientific Officer of Synaffix, said:

We are thrilled with the successful ADC data, expansion of this license agreement and to see a leading global pharmaceutical company like Kyowa Kirin deploying Synaffix ADC technology in order to fulfill its mission of improving the lives of patients with cancer worldwide.

On June 30, 2022 Race Oncology Limited ("Race") reported to share further interim results from our preclinical cardioprotection program in collaboration with researchers from the University of Newcastle (ASX announcement: 28 April 2021) (Press release, Race Oncology, JUN 30, 2022, View Source [SID1234616398]). This program aimed at exploring the use of Zantrene (bisantrene dihydrochloride) as a cardioprotective agent which offered synergy with anti-cancer treatments.

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Zantrene was found to protect the hearts of mice from the damaging effects of anthracyclines (specifically doxorubicin) even when the chemotherapeutic dose was increased without significant additional toxicity or bone marrow suppression.

On June 30, 2022 PureTech Health plc (Nasdaq: PRTC, LSE: PRTC) ("PureTech" or the "Company"), a clinical-stage biotherapeutics company dedicated to discovering, developing and commercializing highly differentiated medicines for devastating diseases, reported the initiation of a clinical study of LYT-100 (deupirfenidone), PureTech’s wholly-owned therapeutic candidate for the potential treatment of idiopathic pulmonary fibrosis (IPF), to support its registration-enabling package (Press release, PureTech Health, JUN 30, 2022, View Source [SID1234616397]). LYT-100 is a selectively deuterated form of pirfenidone. Pirfenidone is a proven therapy for IPF, a devastating condition where the favorable tolerability, safety and potentially higher exposure of LYT-100 could have an important impact on patient adherence and outcomes.

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"The initiation of this study is supported by substantial clinical data demonstrating favorable safety and tolerability of LYT-100," said Julie Krop, M.D., Chief Medical Officer of PureTech. "The unique profile of LYT-100, coupled with the established efficacy of pirfenidone, has the potential to significantly improve care for these patients. We believe that enabling patients to stay on a therapeutic dose longer – even at a dose with comparable exposure to the FDA-approved dose of pirfenidone – has the potential to drive better efficacy. In addition, achieving higher exposure levels than the FDA-approved dose of pirfenidone has the potential to offer even better efficacy, which is our rationale for pursuing a higher dose of LYT-100 in this study. We are excited to be taking this important step towards our goal of helping patients with this devastating condition."

IPF is a chronic orphan condition that causes progressive scarring of the lungs, and approximately 130,000 people in the U.S. are living with the disease. The prognosis of IPF is poor, with the median survival after diagnosis generally estimated at two to five years. Pirfenidone is approved by the U.S. Food and Drug Administration (FDA) for IPF, yet there are serious limitations to pirfenidone’s clinical use, primarily due to severe gastrointestinal (GI)-related tolerability issues.1,2

"Pirfenidone has proven efficacy to slow the decline in lung function in patients with IPF. However, many patients with IPF who start pirfenidone have side effects that cause them to either discontinue therapy or reduce their dose," said Kevin Flaherty, M.D., Professor of Internal Medicine at the University of Michigan specializing in IPF and other interstitial lung diseases and an advisor to PureTech. "I am excited by the safety and tolerability data generated to date with LYT-100, particularly the most recent data demonstrating how well-tolerated it was in a relatively sick, older patient population with multiple comorbidities, as I believe it could represent great potential in patients with IPF."

LYT-100 is designed to retain the potent and clinically validated anti-fibrotic and anti-inflammatory activity of pirfenidone but has demonstrated a highly differentiated pharmacokinetic (PK) profile that has translated into improved tolerability in PureTech’s ongoing clinical development program. To date, LYT-100 has been studied in more than 400 subjects and demonstrated a favorable safety and tolerability profile. In a crossover study in healthy older adults with similar median age to patients with IPF, PureTech showed that approximately 50% fewer subjects experienced GI-related adverse events (AEs) with LYT-100 compared with pirfenidone (17.4% vs. 34.0%) and substantially fewer subjects experienced AEs with LYT-100 vs. pirfenidone. PureTech also recently showed that LYT-100 can be safely dosed with a higher total drug exposure than the currently approved dose of pirfenidone, which could translate into improved efficacy over pirfenidone.

The global, randomized, placebo-controlled registration-enabling study is designed to evaluate the efficacy, tolerability, safety and dosing regimen of LYT-100 to help inform the study design for a potential pivotal study and to assess the relative efficacy of LYT-100 compared to pirfenidone. A total of approximately 240 patients will be randomized 1:1:1:1 to receive either one of two dose levels of LYT-100, the FDA-approved dose of pirfenidone, or a placebo. One of the LYT-100 arms will evaluate 550 mg three times a day (TID) of LYT-100, which has previously demonstrated the comparable exposure as the currently approved dose of pirfenidone (801 mg TID), and the other arm will evaluate an 825 mg TID dose of LYT-100, which has demonstrated higher exposure than the currently approved dose of pirfenidone with the potential for improved efficacy. The primary objective of the study is to demonstrate a statistically significant and clinically meaningful difference in the slope of decline in a measure of lung function, Forced Vital Capacity (FVC), in the LYT-100 treatment arms compared to placebo over 6 months. The study will also evaluate safety, tolerability and the slope of FVC decline in the LYT-100 treatment arms compared to pirfenidone, though this analysis is not powered to demonstrate strict non-inferiority. FVC is an established measure of pulmonary function in IPF and has served as the basis for FDA approval of the currently marketed treatments for IPF. Topline results from the study are expected by the end of 2023.

Advancement of LYT-200 Clinical Program

PureTech’s LYT-200 program is also progressing through clinical development. Following the completion of the monotherapy dose escalation portion of the Phase 1 program, PureTech has begun to evaluate weekly doses of LYT-200 and will soon begin to enroll patients in cohorts designed to evaluate LYT-200 in combination with chemotherapy or an anti-PD-1 monoclonal antibody. Results from the single agent cohorts are expected by the end of 2022, and results from the combination cohorts are expected in 2023.

LYT-200 is a fully human IgG4 monoclonal antibody (mAb) designed to inhibit the activity of galectin-9, a key molecule expressed by tumors and immune cells and shown in preclinical models to suppress the immune system from recognizing and destroying cancer cells. The primary objective of the Phase 1 portion of the ongoing adaptive Phase 1/2 study is to assess the safety and tolerability of escalating doses of LYT-200 in order to identify an appropriate dose and dosing interval to carry forward into the Phase 2 portion of the trial. Six cohorts were treated with escalating, bi-monthly doses from 0.2-16 mg/kg, and no dose limiting toxicities were reported to date.

Additionally, compelling preclinical data have been generated with LYT-200 in leukemia models, which will be submitted for presentation in a scientific forum. Based on these data, PureTech plans to initiate a study of LYT-200 as a single agent in leukemia patients by the end of 2022.

"We are very pleased with the progress of our Phase 1 evaluation of LYT-200, which has demonstrated favorable safety and tolerability as a single agent at all doses studied to date without any dose limiting toxicities," said Aleksandra Filipovic, M.D., Ph.D., Head of Oncology at PureTech. "We look forward to the continued evaluation of this novel therapy as a potential treatment for metastatic solid tumors as well as the initiation of clinical studies in leukemia."

About LYT-100

LYT-100 is one of seven therapeutic candidates within PureTech’s Wholly Owned Pipeline. It is a selectively deuterated form of pirfenidone that is designed to retain the potent and clinically-validated anti-fibrotic and anti-inflammatory activity of pirfenidone with a differentiated pharmacokinetic profile that has translated into favorable tolerability, as supported by data from multiple human clinical studies. LYT-100 is being advanced for the potential treatment of conditions involving inflammation and fibrosis, including idiopathic pulmonary fibrosis and breast cancer-related, upper limb secondary lymphedema. PureTech is also exploring the potential evaluation of LYT-100 in other inflammatory and fibrotic conditions such as myocardial and other organ system fibrosis based on the strength of existing clinical data around the use of pirfenidone in these indications.

About LYT-200

LYT-200 is a fully human IgG4 monoclonal antibody targeting a foundational immunosuppressive protein, galectin-9, for the potential treatment of solid tumors, including pancreatic ductal adenocarcinoma, colorectal cancer and cholangiocarcinoma, that are difficult to treat and have poor survival rates. PureTech has presented preclinical data demonstrating high expression of galectin-9 across breast cancer, pancreatic and cholangiocarcinoma samples and found that the highest levels of galectin-9 correlated with shorter time to disease relapse and poor survival. These data suggest that galectin-9 could be significant both as a therapeutic target for a range of cancers and as a cancer biomarker. Preclinical animal and patient-derived organoid tumor models also showed the potential efficacy of LYT-200 and the importance of galectin-9 as a target. LYT-200 is currently being evaluated in a Phase 1/2 adaptive design trial.

On June 30, 2022 Kazia Therapeutics Limited (NASDAQ: KZIA; ASX: KZA), an oncology-focused drug development company, reported an update on recent progress with its two pipeline assets, paxalisib and EVT801, and on recent corporate financing activity (Press release, Kazia Therapeutics, JUN 30, 2022, View Source [SID1234616396]).

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Key Points

EVT801 phase I study protocol has cleared third dose level and is recruiting well.

GBM AGILE pivotal study has opened in France, the fourth country to commence recruitment to the paxalisib arm.

Phase I study of paxalisib in combination with radiotherapy for treatment of brain metastases at Memorial Sloan Kettering Cancer Center has been accepted for presentation at an upcoming academic conference in Q3 CY2022.

ATM financing facility has realized gross proceeds of US$ 2,956,036 for the period ending June 2022, at an average price of $6.08 (approximately AU$ 0.88 per share).

Kazia CEO, Dr James Garner, commented, "Despite a challenging first half equity market for biotech companies, Kazia has continued to make good progress. The GBM AGILE pivotal study is progressing well, and appears on track for data in 2H CY2023, as anticipated. We have been pleased in the first half to see new data presented and milestones delivered from several projects, and we expect that pace to continue and increase during the second half."

EVT801 Phase I Study

The phase I study of EVT801 in patients with advanced cancer continues to recruit well. The drug has recently completed the third of a potential eight dose levels and is anticipated to open recruitment to the fourth dose cohort in the near future. To date, the drug appears generally well-tolerated. Depending on how many dose cohorts are required to establish a maximum tolerated dose (MTD), interim data from the study is anticipated in 2H CY2022 or 1H CY2023.

GBM AGILE

More than forty sites are currently open to the paxalisib arm of GBM AGILE. The first site to commence recruitment to the paxalisib arm in France opened in June 2022, making France the fourth country to join the study, alongside the United States, Canada, and Switzerland.

In January 2022, the Global Coalition for Adaptive Research (GCAR), the sponsor of GBM AGILE, stated that over a thousand patients had been screened to the study, with enrolment rates approximating 0.75 to 1.00 patients per site per month, which is around four times higher than would generally be expected in a clinical study of glioblastoma.

Kazia continues to work closely with GCAR and Simcere Pharmaceutical to open the study in China. Public health measures in some Chinese cities relating to the ongoing COVID pandemic have had a modest impact on operational activities, but it is currently anticipated that the study will open in China during 3Q CY2022.

Paxalisib in Brain Metastases

In June 2022, the company announced that a multi-drug, genomically-guided study in brain metastases run by the Alliance for Clinical Trials in Oncology had seen the paxalisib arm graduate to an expansion cohort in patients with breast cancer brain metastases, having seen positive efficacy signals in the initial exploratory cohort. Paxalisib continues to recruit to the exploratory cohort in two other patient subgroups.

Interim data from a phase I study of paxalisib in combination with radiotherapy for patients with brain metastases run by Memorial Sloan Kettering Cancer Center has been accepted for an oral presentation at an upcoming international conference in Q3 CY2022. Kazia looks forward to sharing data from this presentation as soon as it is available.

Financing

In May 2022, Kazia established a NASDAQ-based at-the-market financing facility with Oppenheimer and Company. For the period ending June 30, 2022, the company has issued 486,281 American Depository Shares (ADSs) under this facility, at an average price of $6.08, for total gross proceeds of US$ 2,956,036 (approximately AU$ 4,256,691). Of note, these shares have been issued at no discount, with no warrant coverage, and with transaction fees approximately half of those associated with traditional financing.