On August 10, 2020 Diffusion Pharmaceuticals Inc. (Nasdaq: DFFN) ("Diffusion" or "the Company"), a cutting-edge biotechnology company developing new treatments for life-threatening medical conditions by improving the body’s ability to deliver oxygen to the areas where it is needed most, reported financial results for the three and six months ended June 30, 2020 and provided a business update (Press release, Diffusion Pharmaceuticals, AUG 10, 2020, View Source [SID1234568922]).

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Highlights from the second quarter of 2020 and recent weeks include:

Initiation of an international clinical development program in hospitalized patients with COVID-19. Low oxygen levels occur as a consequence of damage to the lungs from COVID-19, often resulting in mechanical ventilation and, if that is ineffective, multiple organ failure – the leading cause of death from COVID-19. Diffusion believes that the oxygen-enhancing mechanism of action of TSC could benefit such patients.
The TSC/Covid-19 clinical development program will begin with an open-label lead-in trial which, if successful, will be followed by one or more randomized double-blinded clinical trials. The lead-in trial will test TSC in 24 hospitalized COVID-19 patients at the Romanian National Institute of Infectious Diseases (NIID). Diffusion expects to begin dosing in this study in the third quarter, with data read-out in the fourth quarter of 2020. In addition to safety, the lead-in trial will collect data on possible increased oxygenation, thereby helping the Company determine TSC dosing for follow-on studies.
Following the recent successful completion of the 19-patient open-label, dose-escalation lead-in safety portion of the trial, the Company has continued pursuit of partnership efforts for its Phase 3 INTACT (INvestigating Tsc Against Cancerous Tumors) program with TSC plus standard of care (SOC) for patients newly diagnosed with inoperable glioblastoma multiforme (GBM).
The Company’s Phase 2 160-patient on-ambulance clinical trial testing TSC for the treatment of acute stroke continues, but on a limited basis because of the on-going pandemic. This program, featuring the PHAST-TSC (Pre-Hospital Administration of Stroke Therapy-TSC) trial, will ultimately involve a total of 23 hospitals across urban, suburban and rural areas in Los Angeles County and Central Virginia when conditions permit more robust operations.
On May 29, 2020 the Company") announced that it received written notice from the Nasdaq Listing Qualifications Staff of the NASDAQ Stock Market LLC ("Nasdaq") stating that the Company regained compliance with the applicable Nasdaq minimum bid price continued listing standard and the matter was now closed.
During the quarter, the Company sold common stock raising $10.3 million and also raised $7.6 million from the exercise of outstanding warrants, for net proceeds of $17.9 million during the reporting period.
"This is an exciting time for Diffusion as we prepare for first enrollment in our global clinical trial program using TSC for the treatment of hospitalized COVID-19 patients," said David Kalergis, chairman and chief executive officer of Diffusion. "Given the severity of the worldwide pandemic, regulatory authorities in the U.S. and Europe have put in place measures to expedite the testing of therapeutics and have been generous in their guidance in light of emerging knowledge. Protocol changes based on this guidance have been incorporated into the development program so that data from any patient, wherever located, can be included to help support planned future regulatory filings in both the U.S. and Europe.

"We also raised funds during the quarter, which will largely be used to advance our TSC clinical development plan, with an emphasis on the COVID-19 program," Mr. Kalergis continued. "At quarter-close we had more than $25 million in cash, the largest cash balance on hand since becoming a public company. In addition, to better help our investors, potential partners and the public stay informed, we are currently revamping our website to reflect the impact of our COVID-19 program on TSC’s development, with the revised website launch targeted for later this quarter."

Second Quarter Financial Results

Research and development expenses were $2.2 million for the second quarter of 2020, compared with $1.5 million for second quarter of 2019. The increase was attributable to a $0.6 million increase in costs associated with follow on work for our 19 patient run-in Phase 3 trial for GBM, a $0.3 million increase in expense related to our open-label Phase 1b lead-in trial for TSC in COVID-19 patients, and a $0.3 million increase in associated manufacturing costs as we ramp up the trial. These increases were offset in part by a $0.5 million decrease in costs associated with the delay in our Phase 2 stroke trial due to the COVID-19 pandemic

General and administrative expenses were $1.5 million for the second quarter of 2020, compared with $1.1 million for the second quarter of 2019. The increase was mainly due to higher professional fees, salaries and wages.

Diffusion had cash and cash equivalents of $25.6 million as of June 30, 2020, compared with $14.2 million as of December 31, 2019. During the second quarter the Company completed an offering of 11.4 million shares of common stock for net proceeds of $10.3 million. In addition, the Company received proceeds of $7.6 million from the exercise of 13.0 million warrants and the exchange and exercise of a further 5.0 million warrants. Diffusion believes its cash and cash equivalents as of June 30, 2020 are sufficient to fund operating expenses and capital expenditures, including clinical trials, into the fourth quarter of 2021.

On August 10, 2020 The Executive Board of Biofrontera AG (shares of Biofrontera AG ISIN: DE0006046113) reported that has decided on 27 July 2020, with the approval of the Supervisory Board, to issue a 1.00 % qualified subordinated mandatory convertible bond 2020/2021 (ISIN: DE000A3E4548 / WKN: A3E454). It is divided into up to 2,638,150 qualified subordinated mandatory convertible bearer bonds ("Bonds") with a nominal value of EUR 3.00 each and a total nominal value of up to EUR 7,914,450 (Press release, Biofrontera, AUG 10, 2020, View Source [SID1234568548]). The shareholders or holders of subscription rights were invited by an announcement in the Federal Gazette (Bundesanzeiger) of 29 July 2020 to exercise their subscription rights to the Bonds during normal business hours in the period from 30 July 2020 up to 13 August 2020 (included) to avoid exclusion. It was also provided that the subscription price would be published in the Federal Gazette (Bundesanzeiger) and via an electronic information medium no later than three days before the end of the subscription period.

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The subscription price for each of the Bonds was set at

100 % of their nominal value of EUR 3,00.

Thus, the cash payment for each bond subscribed is EUR 3.00.

On August 10, 2020 Sysmex Corporation (Chairman and CEO: Hisashi letsugu) reported that it has received approval for insurance coverage for blood-based RAS gene mutation testing for colorectal cancer using the OncoBEAM RAS CRC Kit (Press release, Sysmex Inostics, AUG 10, 2020, View Source [SID1234568252]). The coverage went into effect on August 1, 2020.
With this regulatory approval, even when it is difficult to obtain in vivo diagnostics (biopsy) on a sample taken from tumor tissue, RAS gene mutation testing using the kit may be performed with a minimal physical and mental burden on patients when it is necessary, owing to the fact that it uses the patient’s blood as a sample. This will have the effect of optimizing decisions on the administration of anti-EGFR monoclonal antibody drugs. Receipt of insurance coverage will also make it possible for us to provide more patients with testing to allow physicians to select an appropriate treatment method.

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Currently, at the beginning of therapy, colorectal cancer patients treated with medication undergo RAS gene mutation testing using tumor tissue, the results of which inform a decision on whether or not to administer anti-EGFR monoclonal antibody drugs. Several studies have reported that re-challenge of anti-EGFR monoclonal antibody drugs is an effective treatment method for patients with recurrent colorectal cancer after treatment by anti-EGFR monoclonal antibody drugs, and that the RAS gene mutation status may change by the time of re-challenge from what it was in initial therapy. The relevant guidance published by the Japanese Society of Medical Oncology indicates that it is desirable to assess the gene mutation status several times over time to make appropriate re-challenge decisions based on the state at the time of relapse. As such, much has been expected from a practical application of liquid biopsy, which checks the RAS gene mutation status using the patient’s blood samples when biopsy may not be performed easily.
The OncoBEAM RAS CRC Kit is used to test samples of tumor-derived DNA (circulating tumor DNA, or ctDNA) suspended in the blood of colorectal cancer patients. Using BEAMing technology, the kit detects RAS gene mutations with a high degree of sensitivity (mutant allele frequency of no more than 1% in approximately 30% of mutation cases thus detected). As the first colorectal cancer liquid biopsy testing in Japan that provides auxiliary test data to determine the appropriateness of anti-EGFR monoclonal antibody drugs – Cetuximab and Panitumumab (gene recombination) – for patients with colorectal cancer, this product was approved as an in vitro diagnostic reagent in July 2019 and was covered under health insurance from August 1, 2020. Please note that an insurance-covered assay service for colorectal cancer using this product is also due to start in August 2020.
Performance of RAS gene mutation testing when it is necessary and with a minimal physical and mental burden on patients for whom biopsy is challenging to perform is expected to optimize the administration of anti-EGFR monoclonal antibody drugs. On the other hand, there is a possibility that this testing may deem patients whose ctDNA is not sufficiently leaked into the blood to have wild-type RAS, even though RAS gene mutation exists in tumor tissue. For patients with lung metastasis only, it is particularly necessary to prioritize testing using tumor tissue. Sysmex will remain committed to the provision of scientific information so that medical institutions may perform testing properly.
Going forward, Sysmex will continue to contribute to the advancement of personalized medicine by working on expanding testing opportunities for patients and providing testing and diagnostic technologies with high diagnostic value.

On August 10, 2020 Prescient Therapeutics reported that it is advancing to next-stage trials for its personalised treatments for cancer and COVID-19 and has launched a capital raising for up to $6.5m via a Share Purchase Plan (SPP) (Press release, Prescient Therapeutics, AUG 10, 2020, View Source;utm_medium=rss&utm_campaign=prescient-gears-up-for-growth-with-6-5m-raise-as-the-race-to-cure-cancer-heats-up [SID1234565483]).

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The cash raised will see Prescient Therapeutics’ (ASX:PTX) well-funded to progress its expanded pipeline of exciting cancer treatments, including clinical trials of PTX 100 and 200 products, and its cutting edge programs in cell therapy including the new OmniCAR platform for next-generation CAR-T therapies.

At the same time, the company has attracted leading cancer researcher Professor Phillip Darcy to its Scientific Advisory Board.

The SPP share issue is priced at 5.5c, a 15 per cent discount to its volume-weighted average share price prior to the SPP announcement, and it closes August 17.

"We have a diversified pipeline of targeted therapies of medicines that are in clinical stage trials. And, we have a number of cell therapy programs, including CAR-T," chief executive and managing director Steven Yatomi-Clarke said.

"Not only is Prescient the only ASX company undertaking CAR-T programs, we are have an enabling platform from the pioneer of this technology to create next-gen CAR-T therapies."

Prescient’s personalised cancer therapies focus on genetically modifying the proteins or antigens on the T-Cells of patients so they can better fight and defeat cancer.

"T-cells might normally be able to detect cancer cells by recognising certain proteins on their surface. However, cancers evolve and can evade the immune system by changing these proteins. Without these, the T-cells in our immune system can no longer recognise them. And that’s when we come in to fix that, " Yatomi-Clarke said.

CAR-T is a new generation cell therapy for treating cancer that turbo-charges the body’s immune system’s T-Cells to attack and destroy cancer cells. It does so by training these T-cells to recognise the cancer cells.

A sample of a patient’s T-Cells are collected and grown in a laboratory where they are genetically modified, adding a cancer antigen or protein, to create a hybrid T-Cell called a Chimeric Antigen Receptor (CAR).

"We can reprogram these T-Cells to recognise cancer once again because we add our receptor of choice called a CAR-T cell," Yatomi-Clarke said.

"It is a chimera between the patient’s own T-Cells plus a brand new, introduced receptor so the result is a hybrid; a turbo-charged version of the patient’s T-Cells."

The CAR-T field received a boost at the world’s largest cancer conference, when pharma company Johnson & Johnson reported a 100 per cent response rate among patients in a trial for CAR-T therapy for multiple myeloma.

Globally renowned expertise
Prescient has also just announced a well-timed appointment, naming internationally renowned cancer and CAR-T expert Professor Phillip Darcy as a new member of its Scientific Advisory Board.

Professor Darcy is currently National Health and Medical Research Council (NHMRC) senior research fellow and group leader of cancer immunotherapy at the Peter MacCallum Cancer Centre in Melbourne.

"Prescient is pursuing a number of promising approaches in cell therapy, including cell therapy enhancements, that have the potential to significantly broaden and improve existing approaches to CAR-T therapy," Professor Darcy said.

"Another exciting development involves the OmniCAR platform. This approach may pave the way for a new generation of CAR-T cells that are capable of being controllable, targeting multiple antigens, and potentially used as an off-the-shelf product. I am excited to be able to participate in this important work for cancer patients."

Treating multiple cancers
As exciting and groundbreaking as CAR-T is, the current generation of therapies face challenges that limit its application, including safety, cost and flexibility to treat a range of cancers.

OmniCAR is Prescient’s new platform that seeks to address these challenges – creating the next generation of CAR-T therapies that are safer, controllable and flexible.

OmniCAR aims to improve the safety profile of CAR-T and enhance dosage control and T-Cell activity by making CAR-T more flexible and adaptable to treat multiple cancers including tumours.

The therapy is designed to overcome challenges of CAR-T such as time and cost — the treatment can cost $500,000 per patient — as well as safety concerns, and antigen loss that can lead to a patient’s relapse.

OmniCAR can overcome some of the clinical challenges of CAR-T treatments by allowing on-demand activation of CAR-T cells, increased control over side effects, and reduced cost of treatment.

The OmniCAR platform works by creating a modular CAR-T therapy. The solution is elegant in its simplicity, and effective.

The T-cells and the portion that binds to the cancer (the "binder") are administered separately, where they form a fully functional CAR-T inside the patient. The modularity gives control and enables the CAR-T to be re0directed at-will by the clinician.

"Inside the patient they attach like Lego. That simple elegant capability is what enables you to overcome the challenges of conventional CAR-T," Yatomi-Clarke said.

Dosage control is an important feature of OmniCAR, potentially allowing clinicians to have control of CAR-T activity post infusion.

"With OmniCAR, by administering the binder separately you can add increasing amounts and it switches on progressively. For the very first time after infusion the doctor has control which is important," Yatomi-Clarke said.

"This feature alone would be a game-changer because it makes it more accessible and safer to give to patients."

Quality pipeline of cancer treatments
Prescient Therapeutics has other cancer treatments in its PTX 100 and PTX 200 targeted cell therapies.

"They address particular switches that drive cancer. They are targeted therapies that go inside cancer cells and switch off aberrant proteins," Yatomi-Clarke said.

PTX 100 is the only RhoA inhibitor in clinical development that targets RhoA mutations in cancer cells.

A "Basket trial" is underway for PTX 100 to examine the treatment’s effect on different types of solid and blood cancers after the treatment was deemed safe in a previous Phase 1 trial.

"Rarher than focus on the location of the cancer, we focus on the genetic driver of that cancer," he said.

Results from the basket trials are expected in late 2020 and includes research on PTX 100’s impact on gastric, pancreatic, colorectal cancers and T-Cell lymphomas.

PTX 200 is a personalised treatment for breast cancer that selectively kills tumours, and the company is exploring new combinations of the treatment for breast and ovarian cancers.

A trial is underway to examine the application of PTX 200 in acute myeloid leukemia.

COVID-19 treatment trial
Prescient has also partnered with The Doherty Institute in Melbourne, which is researching the application of two of the company’s drugs as a potential treatment for COVID-19.

"We are in the business of cancer [treatment] and that remains our focus. It just so happens that some of the mechanisms that drive cancer also happen to be important for viral infection and replication and we are looking to exploit that," Yatomi-Clarke said.

Both treatments have priority status and results from the Doherty trials are expected in September.

Prescient has filed patents to protect all intellectual property generated in the trials.

On August 10, 2020 Turning Point Therapeutics, Inc. (NASDAQ: TPTX), a precision oncology company developing next-generation therapies that target genetic drivers of cancer, reported financial results and operational updates for the second quarter ended June 30 (Press release, Turning Point Therapeutics, AUG 10, 2020, View Source [SID1234564368]).

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"We achieved many important milestones since our first quarter update in May, including advancing our pipeline of four drug candidates, sharing our preclinical combination data for repotrectinib in KRAS cancer models, raising gross proceeds of $374 million through our May stock offering, completing a strategic agreement with Zai Lab to develop repotrectinib in Greater China and strengthening our team with the hiring of our chief commercial officer, Andy Partridge," said Athena Countouriotis, M.D., president and chief executive officer.

"Turning to the second half of 2020, we remain focused on advancing our pipeline, as we continue to navigate the COVID-19 pandemic and monitor its impact to our timelines. For the TRIDENT-1 Phase 2 registrational study of repotrectinib, site activations and enrollment have improved since our last update in May, and we are planning to report early interim data from the study in the third quarter. Our goal is to achieve full global site activation in the TRIDENT-1 study in early 2021.

"Overall, I am pleased with how our team has adapted and advanced our clinical development during these challenging times and I want to again thank the dedicated health care providers worldwide who continue to treat patients suffering from COVID-19."

Second quarter and recent highlights include:

Progress in the TRIDENT-1 Phase 2 registrational study of repotrectinib, where the company anticipates reporting early interim data in the third quarter. The preliminary efficacy and safety data by physician assessment are expected to be from 30 to 40 patients across multiple Phase 2 cohorts, including registrational and exploratory cohorts. The company’s goal is to achieve full site activation in the study in early 2021.

Three additional trials ongoing, including the Phase 1/2 open-label study to assess repotrectinib in pediatric patients with ALK-, NTRK- or ROS1-positive advanced solid tumors; the Phase 1 study of TPX-0022, Turning Point’s MET/CSF1R/SRC inhibitor; and the Phase 1/2 study of TPX-0046, Turning Point’s RET/SRC inhibitor.

Completing an exclusive license agreement with Zai Lab for the development and commercialization of repotrectinib in Greater China, which includes mainland China, Hong Kong, Macau and Taiwan. Under the terms of the agreement, Zai Lab obtained exclusive rights to develop and commercialize repotrectinib in Greater China and Turning Point Therapeutics will receive a $25 million upfront payment, with the potential to receive up to an additional $151 million in development, regulatory and sales-based milestone payments. Turning Point will also be eligible to receive mid-to-high teen royalties based on annual net sales of repotrectinib in Greater China.

Appointing Andrew Partridge as executive vice president and chief commercial officer. Mr. Partridge has more than 20 years of global pharmaceutical sales and marketing experience leading more than 20 commercial launches across multiple indications, including oncology, hematology and rare diseases.
Second Quarter Financial Update
Operating expenses for the second quarter totaled $32.7 million compared to $18.5 million in the second quarter of 2019. Primary drivers of the year-over-year increase were investments made to develop repotrectinib, TPX-0022 and TPX-0046, as well as personnel expenses.

Excluding a one-time non-cash stock-based compensation charge in the first quarter of $31.4 million, non-GAAP operating expenses for the first half totaled $64 million compared to $32.5 million in the first half of 2019. Year-to-date net cash used in operating activities was $51.2 million.

Cash, cash equivalents and marketable securities at June 30 totaled $710.4 million, an increase of $329.6 million from Mar. 31 driven by proceeds from the company’s May stock offering. Turning Point Therapeutics projects its cash position funds current operations into 2023.

Upcoming Milestones
Key milestones anticipated into early 2021 include:

Early interim data from approximately 30 to 40 patients across multiple TRIDENT-1 Phase 2 cohorts in the third quarter.

Additional preclinical data highlighting the potential for repotrectinib to increase the effectiveness of KRAS-G12C inhibitors in the fourth quarter.

Early interim data from initial patients treated with TPX-0022 in the fourth quarter.

Submitting the IND for TPX-0131 by early 2021.

Early interim data from initial patients treated with TPX-0046 in early 2021