On August 20, 2020 Kazia Therapeutics Limited (ASX: KZA;NASDAQ: KZIA), an Australian oncology-focused biotechnology company, reported that the United States Food and Drug Administration (FDA) has granted Fast Track Designation (FTD) to Kazia’s paxalisib (formerly GDC-0084) for the treatment of glioblastoma, the most common and most aggressive form of primary brain cancer (Press release, Kazia Therapeutics, AUG 20, 2020, View Source [SID1234564080]).

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Key Points

Fast Track Designation (FTD) is designed to expedite development of pharmaceutical products which demonstrate the potential to address unmet medical needs in serious or life-threatening conditions
FTD provides Kazia with substantially enhanced access to FDA, including opportunities for face-to-face meetings and written consultation throughout the remaining development of paxalisib
Drugs with FTD are eligible to apply for Accelerated Approval and Priority Review at the time of a New Drug Application (NDA) submission, which may result in faster product approval
FTD also allows for ‘rolling review’, whereby Kazia may submit completed sections of the paxalisib NDA as they become available, rather than at the end of development
Kazia consequently plans to begin initial preparatory activities for NDA filing for paxalisib in CY2021
Kazia CEO, Dr James Garner, commented, "in awarding Fast Track Designation to paxalisib, FDA has recognised the drug’s potential to meaningfully improve outcomes for patients with glioblastoma. This is a very powerful acknowledgement. The opportunities that Fast Track Designation creates, as we move towards an NDA filing, are of great value and have the potential to substantially accelerate the commercialisation of paxalisib. In particular, the ‘rolling review’ process enables Kazia to complete and submit substantial sections of our NDA filing in advance, saving time and reducing risk for the product. We look forward to working closely with FDA as we move into the final stage of development for paxalisib."

The specific indication for which FTD has been approved is "for the treatment of patients with newly diagnosed glioblastoma with unmethylated O6-Methylguaninemethyltransferase (MGMT) promotor status who have completed initial radiation with concomitant temozolomide." This language precisely reflects the patient population studied in the ongoing phase II study, and is the primary proposed population for the GBM AGILE pivotal study, and is the intended indication at commercial launch.

Kazia announced on 7 August 2020 that FDA had granted paxalisib Rare Pediatric Disease Designation (RPDD) for DIPG, an aggressive childhood brain cancer. For clarity, this granting of FTD for glioblastoma is not specifically connected to the prior granting of RPDD in DIPG.

Fast Track Designation

Introduced under the FDA Modernization Act (1997), Fast Track Designation (FTD) may be awarded by FDA to investigational drugs which treat a serious or life-threatening condition, and which fill an unmet medical need. FDA notes that ‘the purpose [of the Fast Track program] is to get important new drugs to the patient earlier.'[1] FTD must be requested by the sponsor company and must be accompanied by a detailed review of both preclinical and clinical data. To be awarded FTD, drugs must generally be able to show some potential advantage over existing therapies, either in terms of safety or efficacy.

The key benefits of FTD comprise enhanced access to FDA, with regular and more frequent opportunities for consultation and discussion. In addition, drugs with FTD may be eligible for Accelerated Approval, in which a new medicine is approved prior to the availability of definitive data, and Priority Review, in which the standard 12-month review process is reduced to six months. Drugs with FTD may also enter a ‘rolling review’ of their NDA submission, in which sections are submitted and reviewed as they become available, substantially expediting the approval process.

Next Steps

Kazia completed recruitment to its phase II clinical trial of paxalisib in newly diagnosed glioblastoma in February 2020, and interim clinical data was presented at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) Virtual Annual Meeting II in June 2020. Overall survival was calculated at 17.7 months, which compares favourably to a historical figure of 12.7 months for temozolomide, the existing FDA-approved standard of care.

Kazia expects to present further data from this study in 2H CY2020, and to conclude the study in early CY2021.

Paxalisib has been selected to join the international GBM AGILE pivotal study in glioblastoma, and recruitment is expected to begin in 2H CY2020.

On August 20, 2020 Targovax ASA (OSE: TRVX), a clinical stage biotechnology company developing immune activators to target hard-to-treat solid tumors, reported its second quarter and first half 2020 results (Press release, Targovax, AUG 20, 2020, View Source [SID1234564007]).

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An online presentation by Targovax’s management to investors, analysts and the press will take place at 10:00 CET today (details below).

HIGHLIGHTS FOR THE SECOND QUARTER AND FIRST HALF 2020
Data
Announced encouraging clinical and immune data in mesothelioma combining ONCOS-102 and chemotherapy demonstrating that ONCOS-102 activates patients’ immune system far more extensively than chemotherapy
Presented interim data from safety lead-in cohort in the ovarian and colorectal (peritoneal metastasis) trial at ASCO (Free ASCO Whitepaper)
Presented pre-clinical data from Next Generation ONCOS at AACR (Free AACR Whitepaper)
Completed enrollment in the melanoma trial
Collaborations
Entered into a collaboration with Merck to test ONCOS-102 in combination with Keytruda and chemotherapy in mesothelioma
Entered into a collaboration with Leidos to equip ONCOS viruses with genetic elements encoding for small peptides with checkpoint inhibitor functionality
Entered into an option agreement with IOVaxis Therapeutics for a TG mutant RAS vaccine license agreement in Greater China and Singapore
Entered into a collaboration to develop mutant RAS neoantigen coating of ONCOS viruses using Valo Therapeutic’s PeptiCRAd technology
Entered into a collaboration with Oblique Therapeutics to target mutant RAS cancers by combining both companies’ technology platforms
Corporate
Completed a private placement, raising NOK 101 million (USD 11.2 million)
Announced election of Damian Marron as Chairman of the Board
Appointed Dr Victor Levitsky, MD, PhD as CSO
Øystein Soug, CEO commented: "Targovax had a highly productive second quarter this year. Most importantly, we reported 12-month immune and efficacy data for ONCOS-102 in mesothelioma, our lead indication, in combination with standard of care chemotherapy (SoC). Based on the promising findings so far, we have started preparations for a subsequent randomized phase II trial where we will add a checkpoint inhibitor to the ONCOS-102 and chemotherapy combination. We are very pleased to have secured a clinical collaboration agreement with Merck for this trial, who will provide Keytruda and valuable scientific and clinical support for the trial. Additionally, three new innovative collaborations, of which two of them were RAS collaborations, were signed during the quarter, indicating a high interest in Targovax."

Presentation
As a consequence of the Corona situation, there will not be a physical presentation of the results. Instead, we invite to a live webcast today at 10.00 CET. You can join the webcast here. It will be possible to ask questions during the presentation.

On August 20, 2020 Moffitt Cancer Ctr reported that World-renowned tumor immunologist Patrick Hwu, M.D., has been appointed the new president and CEO of Moffitt Cancer Center (Press release, Moffitt Cancer Ctr, AUG 20, 2020, View Source [SID1234563959]). He joins Moffitt from The University of Texas MD Anderson Cancer Center, where he is the division head of Cancer Medicine. Hwu begins his new role at Moffitt on Nov. 10.

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Patrick Hwu, M.D., president and CEO, Moffitt Cancer CenterPatrick Hwu, M.D., president and CEO, Moffitt Cancer Center
"Dr. Hwu is truly a cancer visionary ready to elevate Moffitt to even greater success," said Tim Adams, chair of Moffitt’s Institute Board of Directors. "Drawing from his innovative cancer research, quality patient care and extensive leadership experience, Dr. Hwu will no doubt continue to help Moffitt in our pursuit of dynamic growth and groundbreaking work."

"It is my distinct honor and privilege to be selected as the next president and CEO of Moffitt Cancer Center, which has made unprecedented strides in its 34 years in the prevention and treatment of cancer," Hwu said. "I look forward to bringing my years of experience as a cancer physician, researcher and leader to help advance the outstanding work already underway by the teams of cancer experts at Florida’s top-ranked cancer hospital. I’m confident that our collective efforts will further elevate Moffitt’s leadership in cancer patient care, research and education."

Hwu brings 33 years of oncology experience to Moffitt. He held various leadership roles during 17 years at MD Anderson, including chair of the Department of Sarcoma Medical Oncology and co-director of the Center for Cancer Immunology Research. He was the first chair of the Department of Melanoma Medical Oncology. Known for leading transformative research into the clinic, Hwu helped pioneer the field of gene modified T cells, publishing research on the first chimeric antigen receptor directed against cancer. His work focuses on vaccines, adoptive T-cell therapies and immune resistance. He is the principal investigator on a National Institutes of Health SPORE grant for melanoma and has more than 270 peer-reviewed publications.

Hwu is vice president/president elect at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper), serves on the Melanoma Research Alliance Foundation Medical Advisory Panel in Washington, D.C., and is a member of numerous scientific advisory boards throughout the U.S.

Founder H. Lee MoffittFounder H. Lee Moffitt
"Dr. Patrick Hwu is a nationally respected physician-scientist with the vision to lead Moffitt into the future," said founder H. Lee Moffitt. "Coming from the largest cancer center in the country, where he has distinguished himself and produced incredible results, we expect he will successfully guide the Moffitt team through the next generation of cancer treatments and discoveries.

"I’m confident Dr. Hwu will inspire and continue our mission to contribute to the prevention and cure of cancer. Our impact on helping cancer patients will be felt worldwide and, in the process, continue to make Florida proud," Moffitt said.

Russell Reynolds Associates, a global leadership advisory and search firm, led the extensive and competitive national search.

Hwu earned his medical degree from The Medical College of Pennsylvania. He served as a house officer in Internal Medicine at The Johns Hopkins Hospital and completed a fellowship in oncology at the National Cancer Institute.

On August 20, 2020 Merck & Co reported that Checkpoint inhibitors that unleash the immune system so it can fight cancer have proven powerful in many tumor types (Press release, Merck & Co, AUG 20, 2020, View Source [SID1234563950]). But their efficacy rests on the premise that patients’ T cells can launch an attack against tumors on their own. That’s why scientists are looking for ways to improve immuno-oncology by drawing T cells to the tumor microenvironment.

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Activating a pathway called cGAS-STING is one potential strategy that has been shown to stimulate T cell recruitment to the tumor microenvironment. Now, scientists at Merck & Co. have designed a STING agonist that can be taken by mouth.

The drug, dubbed MSA-2, cleared tumors in mice bearing colorectal cancer. In tumor models that were poorly responsive to PD-1 blockade, combining MSA-2 and inhibition of the checkpoint PD-1 outperformed monotherapy at controlling tumor growth and prolonging survival, according to results published in Science.

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A Merck spokesperson said the company doesn’t yet have a plan to advance MSA-2 into clinical testing.

Merck already has a STING agonist in development, MK-1454. But MK-1454 failed to produce any responses on its own in patients with advanced solid tumors or lymphomas in a phase 1 trial. There was a 24% response rate to a combination of MK-1454 and Keytruda, the company’s blockbuster PD-1 inhibitor.

Another problem with first-generation STING agonists like MK-1454 is that they must be dosed by directly injecting tumors, which limits their application to just a small number of cancer types. These initial molecules were designed as analogs of cyclic dinucleotide (CDN), which STING binds to, but they are unstable and can induce inflammatory cytokines when administered into the circulatory system.

The Merck researchers set out to identify a non-CDN-based STING agonist that’s suitable for systemic delivery. They used a screen to detect stimulation of interferon beta, a known effect of STING activation, and eventually landed on MSA-2.

RELATED: Aduro stung as Novartis drops work on STING drug

The researchers administered MSA-2 by intratumoral, subcutaneous or oral routes in a mouse model of colorectal cancer. The drug was well tolerated and induced complete tumor regressions in 80% to 100% of treated animals. Even after mice that had no signs of cancer were re-challenged with malignant cells, 95% of the animals remained tumor-free, suggesting long-term anticancer immunity, the team reported.

What’s more, in four mouse tumor models of advanced colorectal cancer, melanoma and lung tumors that were not responsive to PD-1 blockade, combinations of PD-1 blockade and MSA-2 led to better inhibition of tumor growth and extended lives of the rodents compared with either drug alone.

STING is a hot yet challenging target in immuno-oncology. MK-1454, after its initial disappointment, is now being evaluated alongside Keytruda in a phase 2 trial in head and neck squamous cell carcinoma. Aduro Biotech, which is on track to merge with Chinook Therapeutics, also has an intratumoral candidate, ADU-S100. Novartis previously licensed that drug in a $200 million upfront deal only to return it after lackluster clinical data.

GlaxoSmithKline is developing GSK3745417, which can be administered intravenously. Bristol Myers Squibb, through its 2017 acquisition of IFM Therapeutics, has BMS-986301, which is being paired with Opvido and Yervoy in solid tumors. Other STING players include Nimbus Therapeutics as well as Takeda, which is working with Curadev on a candidate.

In a separate Science study, researchers at Scripps Research and the California Institute for Biomedical Research also described a non-CDN STING agonist, dubbed SR-717. The drug demonstrated robust anti-tumor activities in a mouse model of melanoma with a level of efficacy in terms of tumor burden and overall survival that was superior than that for PD-1/L1 therapy.

"Non-nucleotide small-molecule STING agonists that can be administered systemically may represent an attractive approach for targeting this path­way and have the potential to transform the therapeutic landscape once optimized," wrote two University of Chicago scientists in a related Perspective in Science.

On August 20, 2020 Junshi Biosciences, a Shanghai biopharma, reported a JV with Nanjing’s Impact Therapeutics to develop Impact’s PARP inhibitor (Press release, ChinaBio, AUG 20, 2020, View Source [SID1234563932]). Junshi will contribute $43 million for 50% of the JV while Impact will add Greater China rights to IMP4297, the company’s clinical-stage PARP inhibitor. The two companies will collaborate on conducting clinical trials of the candidate in multiple indications, starting with ovarian cancer, plus preparing for manufacturing and commercialization.

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