On November 18, 2021 Xspray Pharma (publ) (Nasdaq Stockholm: XSPRAY) reported that the application for US market approval of its first product candidate Dasynoc (dasatinib) has been submitted, in accordance with plans, to the Food and Drug Administration (FDA) under the 505(b)(2) NDA procedure, which is the registration path that applies to improved drugs (Press release, Xspray, NOV 18, 2021, View Source [SID1234649575]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The application consists of the results from the registrational studies on healthy volunteers, where bioequivalence was achieved at about 30 percent lower dosage than the original drug, Sprycel. The studies confirms that:

Dasynoc is unaffected by the pH value of the stomach, and can thus be used in combination with proton-pump inhibitors such as omeprazole for treatment of peptic ulcers
Dasynoc has significantly lower variability than Sprycel, and did not demonstrate cases where there was no uptake of dasatinib at all in the subjects the uptake of Dasynoc is not affected by food intake Dasynoc can be administered at a lower dosage than the reference product, which is expected to yield fewer side effects
Under the application procedure, the FDA has up to 60 days to conduct an initial review of the company’s application, and afterward will announce whether the application is ready to continue to a complete review or if additional information is needed. If the application moves on to a full review, approval will take ten months but may also take longer depending on the questions from the FDA during the review process. The application will be supplemented with stability data for lower dosages of Dasynoc. The point in time at which this is to be done will be determined in consultation with the FDA.

The application includes Dasynoc for the treatment of acute lymphoblastic leukemia (ALL) and chronic myeloid leukemia (CML), which are blood cancer indications in an area where only one new drug has been registered for a number of years. The leading product, Sprycel, sold globally for USD 2.1 billion in 2020, of which USD 1.3 billion was in the US.

"This is our first application for market approval, and it marks a major milestone for Xspray Pharma. Our unique technology is especially suited to overcoming many of the shortcomings that PKI substances generally possess, and the technology is applicable to a majority of the 72 PKIs being marketed today. In this way, we are now developing a portfolio of improved PKI drugs that create value for the company and make better quality of life possible for patients," says CEO Per Andersson.

On November 18, 2021 Tempest Therapeutics, Inc. (Nasdaq: TPST), a clinical-stage oncology company developing potentially first-in-class therapeutics that combine both tumor-targeted and immune-mediated mechanisms, reported the first patient has been dosed with TPST-1495 in combination with pembrolizumab in the Phase 1a/1b open-label, dose and schedule optimization study of TPST-1495 in patients with solid tumors (Press release, Tempest Therapeutics, NOV 18, 2021, View Source [SID1234595775]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"We’re very pleased to announce the start of patient dosing with TPST-1495 in combination with pembrolizumab," said Sam Whiting, MD, Ph.D., chief medical officer of Tempest. "TPST-1495 is designed to inhibit key components of the Prostaglandin E2, or PGE2, pathway, which is both a driver of tumor cell proliferation and an important suppressor of anti-tumor immune function. In addition, recent data show that PGE2 is involved in enabling tumors to escape from immune checkpoint inhibitors such as pembrolizumab, a process known as adaptive immune resistance. Based on this mechanistic rationale and our preclinical data, we are excited about the potential of this combination to be superior to either approach alone and bring benefit to patients."

The first-in-human Phase 1a/1b, multicenter, open-label, dose and schedule optimization study is being conducted at academic and Phase 1 sites in the U.S. and evaluates TPST-1495 as a single agent and in combination with pembrolizumab to determine its maximum tolerated dose and/or recommended Phase 2 dose, safety, tolerability, pharmacokinetics, pharmacodynamics and preliminary anti-tumor activity in subjects with advanced solid tumors. The preliminary dose-finding stage of the study allows patients with any solid tumor histology, while the study expansion stages are designed both to focus upon patients with prostaglandin-driven cancers, including colorectal cancer, endometrial cancer, squamous cell carcinoma of the head and neck, as well as biomarker-selected patients with tumor-driver mutations in the PIK3CA gene, which are known to enhance the level of prostaglandin production in tumor cells.

About TPST-1495

TPST-1495 is an orally available small molecule designed to block the tumor-promoting EP2 and EP4 receptors in the prostaglandin (PGE2) pathway, while sparing the homologous but immune-supporting EP1 and EP3 receptors. PGE2 signaling through EP2 and EP4 has been observed both to enhance tumor progression and promote immune suppression. Tempest has conducted head-to-head preclinical studies comparing TPST-1495 to single antagonists of EP2 and EP4 and observed significantly enhanced activity of TPST-1495 in both overcoming PGE2-mediated suppression of human immune cells in vitro, as well as significantly increased anti-tumor activity in mouse models of human colorectal cancer. Tempest is currently evaluating the safety, tolerability, pharmacokinetics, pharmacodynamics, and possible anti-tumor activity of TPST-1495 as a single agent and in combination with pembrolizumab in a multicenter Phase 1a/1b dose and schedule optimization study in subjects with advanced solid tumors.

On November 18, 2021 Exact Therapeutics AS ("EXACT-Tx", or "the Company" Euronext Growth: EXTX), a clinical-stage precision health company evaluating Acoustic Cluster Therapy (ACT) across multiple therapeutic areas, reported a number of strategic, operational and scientific developments (Press release, Exact Therapeutics, NOV 18, 2021, View Source [SID1234595791]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

As reported in May 2021, EXACT-Tx plans to file a protocol amendment regarding its ACTIVATE phase 1 clinical trial with the UK MHRA. Following approval, the Company plans to recommence enrolment in the trial at the Royal Marsden Hospital London / Institute of Cancer Research with the recruitment of patients in the part 1 cohort planned to be completed by mid 2022. The study aims to evaluate the combination of PS101 ACT with standard of care chemotherapy for treatment of liver metastases in patients with metastatic colorectal cancer A number of valuable and encouraging insights have been gained from this first cohort of treated patients particularly with respect to the application of ultrasound.

The Company also announces that it aims to start its first clinical trial in the USA to evaluate ACT in pancreatic cancer patients. In the USA there are approximately 60,000 newly diagnosed cases of pancreatic cancer and approx. 50,000 deaths per year. The Company expects to submit IND filing to the FDA by mid 2022 which, if approved, will be followed by the start of the clinical trial towards the end of 2022. Today, the 18th of November, is Pancreatic Cancer Awareness Day, and EXACT-Tx is committed to play its role in fighting this aggressive disease.

EXACT-Tx is pleased to announce that Co-Founder Dr Andrew ("Andy") Healey has returned to the Company as Chief Scientific Officer. Andy brings over 20 years experience in the life sciences industry, primarily working with contrast agents and optical molecular imaging, physics, instrumentation, characterisation and clinical imaging systems & trials. The Company’s management team has been significantly strengthened this year with the appointments of Dr Hilary McElwaine-Johnn as Chief Medical Officer and Dominic Moreland as Chief Financial Officer and subsequently Interim Chief Executive Officer.

Strong preclinical data on ACT were recently published in The Journal of Controlled Release 1 which demonstrated that ACT safely and temporarily increased the permeability of the Blood Brain Barrier ("BBB") in animal models as well as increased the penetration and accumulation of co-administered compounds including nanoparticles with no treatment related tissue damage observed. The BBB remains a formidable challenge to the delivery of drugs into the brain. The published preclinical data demonstrates that ACT could be a potential strategy to overcome this obstacle and promote efficient and specific crossing through BBB of therapeutically relevant agents, addressing a huge unmet medical need and further demonstrating the power of the ACT platform. "We have demonstrated that ACT has the ability to open the BBB in a pre-clinical model to deliver large molecules and nano particles with no observable damage to the brain. This approach is an exciting and evolving field that has the promise to deliver drug and to treat the central nervous system." says Professor Catharina de Lange Davies, Dept. of Physics, Norwegian University of Science and Technology (NTNU), and co-author of the paper.

Dr Masha Strømme, Executive Chair of the Board, stated: "We have significantly strengthened our team over the last few months and are well positioned to maximise the value of our innovative Acoustic Cluster Therapy (ACT) platform for ultrasound enhanced drug targeting which has the potential to significantly amplify the clinical utility of a wide range of therapeutic agents across most drug classes and improve upon standard of care. I am very pleased to welcome Andy whose technical expertise and industry know-how coupled with his longstanding commitment to EXACT-Tx is a very strong addition to the leadership team. I look forward to working with him again as we further investigate this exciting approach to ultrasound mediated therapeutic targeting."

On November 18, 2021 Tempus, a leader in artificial intelligence and precision medicine, reported that it is working with Epic to offer providers in-workflow integrations at scale (Press release, Tempus, NOV 18, 2021, View Source [SID1234595809]). Since its founding, Tempus has strived to provide physicians seamless access to next-generation sequencing and the accompanying data to support them in providing personalized patient care.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Through Epic’s Genomics module, Tempus has been paving the way with live EHR integrations that embed test ordering and discrete genomic data delivery into the existing clinical workflow, with 8 institutions already live and a number underway. Tempus’ initial work with Epic made it the first somatic sequencing lab in the country creating these types of integrations.

"Tempus understands our need for efficient, streamlined ordering and reliable discrete results all in one place so that we can promptly implement the actionable results for our patients," said Karen Huelsman, MS, LGC, Precision Oncology Lead at TriHealth Precision Oncology. "More than that, Tempus continually works with our precision oncology team to optimize the integration and apply Epic’s Genomics module components to fit our specific, changing needs."

Tempus is building on that existing work to accelerate and scale this endeavor. In 2022, Epic and Tempus expect to support large-panel genomic sequencing testing across the Epic network. This new capability is designed to reduce integration timelines from months to weeks and make it significantly easier for health systems to enable Tempus testing options within their Epic EHR.

"We realized that we could significantly reduce the amount of time physicians spend ordering Tempus’ smart diagnostics and viewing results at the point of care, ultimately freeing up more time for them to spend with their patients," said Terron Bruner, Chief Commercial Officer of Tempus. "Epic introduced the technology we needed to make these kinds of integrations not only possible, but also seamless for providers, like TriHealth, seeking these solutions."

"Our work with Tempus presents a tremendous opportunity to advance precision medicine by empowering providers and patients with insights from integrated genomic data," said Alan Hutchison, Vice President of Population Health at Epic. "Together we can deliver on the promise of precision medicine and positively impact early detection, treatment, and survival."

On November 18, 2021 ESSA Pharma Inc. ("ESSA", or the "Company") (NASDAQ: EPIX), a clinical-stage pharmaceutical company focused on developing novel therapies for the treatment of prostate cancer, reported financial results for the fiscal year ended September 30, 2021 (Press release, ESSA, NOV 18, 2021, View Source [SID1234595828]). All references to "$" in this release refer to United States dollars, unless otherwise indicated.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"2021 has been a year of meaningful execution on all aspects of the development program of EPI-7386, our highly-selective, oral, small molecule inhibitor that uniquely targets the N-terminal domain of the androgen receptor for the treatment of patients with metastatic castration-resistant prostate cancer ("mCRPC")," stated David Parkinson, MD, President and CEO of ESSA. "During the year, we presented initial clinical data at a scientific conference that suggest a favorable pharmacological profile and provide clinical proof of concept for EPI-7386. In addition, we demonstrated through nuclear magnetic resonance ("NMR") studies that EPI-7386 binds to the N-terminal domain of the androgen receptor—the primary driver of prostate cancer growth. We were pleased to announce this year clinical collaborations with Janssen Research and Development LLC ("Janssen"), Astellas Pharma Inc. ("Astellas"), and Bayer, three leading companies with approved antiandrogen treatments for prostate cancer. These Phase 1/2 studies, anticipated to begin in late 2021 or early 2022, will evaluate EPI-7386 in combination with the companies’ respective antiandrogen therapies in earlier line mCRPC patients."

Dr. Parkinson continued: "As a result of the successful financing earlier this year, our cash and short-term investments of $195 million are expected to provide us a cash runway into 2024 and fully fund the current development programs, including the Phase 1a/1b monotherapy studies, Phase 2, preparatory work for a Phase 3 confirmatory study as well as commitments around the four Phase 1/2 combination studies with approved antiandrogens. In the Phase 1 monotherapy dose escalation study, we are currently dosing patients with EPI-7386 at 800 mg administered as 400 mg BID, and our goal remains to establish a recommended Phase 2 dose ("RP2D") for monotherapy during the first half of 2022, while commencing the expansion Phase 1b study soon thereafter. We look forward to presenting a clinical readout of the Phase 1a monotherapy trial in the first half of 2022."

Clinical and Corporate Highlights for 2021 Fiscal Year

On October 7, 2021, at the 2021 American Association for Cancer Research (AACR) (Free AACR Whitepaper) ("AACR"), National Cancer Institute ("NCI"), and European Organisation for Research and Treatment of Cancer ("EORTC") Virtual AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper), the Company presented preclinical data characterizing the mechanism of action of EPI-7386, including the results of NMR studies which confirm the binding of the compound to the N-terminal domain ("NTD") of the androgen receptor ("AR"), a region not currently targeted by other antiandrogen therapies. The data also demonstrate that the combination of EPI-7386 with enzalutamide results in complete inhibition of genome-wide androgen-induced AR binding, supporting the rationale for Phase 1/2 combination trials of EPI-7386 with approved antiandrogens in patients with mCRPC.
On April 28, 2021, the Company announced a clinical collaboration with Bayer to evaluate EPI-7386 in combination with Bayer’s androgen receptor inhibitor darolutamide in patients with mCRPC. Under the terms of the agreement, Bayer may sponsor and conduct a Phase 1/2 study to evaluate the safety, pharmacokinetics and efficacy of the combination of EPI-7386 and darolutamide in mCRPC patients. ESSA will supply EPI-7386 for the trial and will retain all rights to EPI-7386.
On April 10, 2021, the Company reported new preclinical data on EPI-7386 at the 2021 AACR (Free AACR Whitepaper) Annual Meeting demonstrating that in vitro EPI-7386 can prevent the androgen receptor from binding to genomic DNA and can inhibit AR related transcription in prostate cancer cell lines expressing AR splice variants including the AR-v567es variant. The results also demonstrate that combining EPI-7386 with enzalutamide in vitro results in a broader and deeper inhibition of the AR pathway.
On February 25, 2021, the Company announced a clinical collaboration with Astellas Pharma Inc. to evaluate the combination of EPI-7386 and Astellas/Pfizer’s androgen receptor inhibitor enzalutamide for patients with mCRPC. Under the terms of the agreement, ESSA will sponsor and conduct a Phase 1/2 study to evaluate the safety, tolerability and preliminary efficacy of the combination of EPI-7386 and enzalutamide in mCRPC patients who have not yet been treated with second-generation antiandrogen therapies. Astellas will supply enzalutamide for the trial. ESSA will retain all rights to EPI-7386.
On February 22, 2021, the Company completed an underwritten public offering for aggregate gross proceeds of $149,999,985, issuing a total of 5,555,555 common shares, at a public offering price of $27.00 per share.
On February 11, 2021, the Company presented favorable initial Phase 1 clinical pharmacology data of EPI-7386 for advanced forms of prostate cancer at the 2021 ASCO (Free ASCO Whitepaper) Genitourinary Cancers Symposium.
On January 13, 2021, the Company announced a clinical collaboration with Janssen to evaluate EPI-7386 in combination with abiraterone acetate/prednisone or apalutamide for patients with mCRPC. Under the terms of the agreement, Janssen may sponsor and conduct up to two Phase 1/2 studies evaluating the safety, tolerability and preliminary efficacy of the combination of EPI-7386 and apalutamide as well as the combination of EPI-7386 with abiraterone acetate plus prednisone in patients with mCRPC. Janssen will assume all costs associated with these studies other than the manufacturing costs associated with the clinical drug supply of EPI-7386. The parties will form a joint oversight committee for the clinical studies. ESSA will retain all rights to EPI-7386.
Summary Financial Results

Net Loss. ESSA recorded a net loss of $36.8 million ($0.96 loss per common share based on 38,480,378 weighted average common shares outstanding) for the year ended September 30, 2021, compared to a net loss of $23.4 million ($1.04 loss per common share based on 22,443,893 weighted average common shares outstanding) for the year ended September 30, 2020. For the year ended September 30, 2021, this included non-cash share-based payments of $9.5 million compared to $7.5 million for the prior year, recognized for stock options granted and vesting. The net loss for the fourth quarter ended September 30, 2021 was $8.5 million compared to a net loss of $4.6 million for the fourth quarter ended September 30, 2020.

Research and Development ("R&D") expenditures. R&D expenditures for the year ended September 30, 2021 were $24.3 million compared to $12.1 million for the year ended September 30, 2020 and includes non-cash costs related to share-based payments ($3.6M for year ended 2021 compared to $1.9M for year ended 2020). For the fourth quarter ended September 30, 2021, R&D expenditures were $6.3 million (net and gross), as compared to $2.2 million (net and gross) for the fourth quarter ended September 30, 2020. The increase in R&D expenditures for the full year and fourth quarter were primarily related to preclinical work leading to the filing of the IND for EPI-7386 in March 2020, the increased expenditure on chemistry and manufacturing of drug product, and clinical costs related to the Phase 1 clinical trial of EPI-7386 which commenced with the dosing of the first patient in July 2020.

General and administration ("G&A") expenditures. G&A expenditures for the year ended September 30, 2021 were $12.9 million compared to $11.4 million for the year ended September 30, 2020 and include non-cash costs related to share-based payments of $5.8M for the year ended 2021 compared to $5.6M for the year ended 2020. For the fourth quarter ended September 30, 2021, G&A expenditures were $2.9 million, compared to $2.2 million for the fourth quarter ended September 30, 2020. The increase in the full year and fourth quarter is the result of increased professional fees related to transitioning to be a domestic filer, higher salaries and benefits, as well as the non-cash share-based payments.
Liquidity and Outstanding Share Capital

At September 30, 2021, the Company had available cash reserves and short-term investments of $194.9 million, reflecting the gross proceeds of the February 2021 financing of approximately $150.0 million and July 2020 financing of $48.9 million, less operating expenses in the intervening period.

As of September 30, 2021, the Company had 43,984,346 common shares issued and outstanding.

In addition, as of September 30, 2021 there were 3,234,750 common shares issuable upon the exercise of warrants and broker warrants. This includes 2,920,000 prefunded warrants at an exercise price of $0.0001, and 314,750 warrants at a weighted average exercise price of $4.84. There were 6,803,230 common shares issuable upon the exercise of outstanding stock options at a weighted-average exercise price of $5.20 per common share.

About EPI-7386
EPI-7386 is an investigational, highly-selective, oral, small molecule inhibitor of the N-terminal domain of the androgen receptor. EPI-7386 is currently being studied in a Phase 1 clinical trial (NCT04421222) in men with mCRPC whose tumors have progressed on current standard-of-care therapies. The Phase I clinical trial of EPI-7386 began in calendar Q3 of 2020 following FDA allowance of our Investigational New Drug application and Health Canada acceptance. The U.S. FDA has granted Fast Track designation to EPI-7386 for the treatment of adult male patients with mCRPC resistant to standard-of-care treatment. ESSA retains all rights to EPI-7386 worldwide.