On August 11, 2020 Cardiff Oncology, Inc. (Nasdaq: CRDF), a clinical-stage oncology therapeutics company developing drugs to treat cancers with the greatest medical need for new treatment options, including KRAS-mutated colorectal cancer, castrate-resistant prostate cancer and leukemia, reported company highlights and financial results for the second quarter ended June 30, 2020 (Press release, Cardiff Oncology, AUG 11, 2020, View Source [SID1234563424]). The Company is issuing this press release in lieu of conducting a conference call.

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"I am very pleased with the progress we made during the second quarter, as we achieved numerous clinical, regulatory and corporate milestones that have driven our sustained growth," said Dr. Mark Erlander, chief executive officer of Cardiff Oncology. "We announced compelling clinical data demonstrating the safety and efficacy of ovansertib in combination with standard-of-care therapy in KRAS-mutated metastatic colorectal cancer. Additionally, we announced the positive efficacy and safety results of the Phase 1b portion of our trial in relapsed/refractory acute myeloid leukemia and we continue to advance our Phase 2 trial in metastatic castrate-resistant prostate cancer, highlighting the broad commercial opportunity offered by the continued development of onvansertib. Notably, in the second quarter, we secured financing of $25 million from equity investments by biotech-focused institutional investors Acorn Bioventures LP and CAM Capital, the exercise of warrants and funding for clinical study commitments, which have left us well positioned to complete our ongoing clinical trials and continue advancing development of onvansertib."

Program highlights for the quarter ended June 30, 2020 include:

KRAS-mutated Metastatic Colorectal Cancer (mCRC) Program:

Presented data further demonstrating the efficacy of onvansertib in patients with KRAS-mutated mCRC at the 2020 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting.

Newly announced data from a Phase 1b/2 clinical trial demonstrate the safety and efficacy of onvansertib, an oral and highly selective Polo-like Kinase 1 (PLK1) inhibitor, in combination with FOLFIRI and Avastin (bevacizumab) in second line KRAS-mutated mCRC patients. These data were featured in a virtual poster presentation at the 2020 ASCO (Free ASCO Whitepaper) Annual Meeting. Data highlights from the presentation included:

Onvansertib-FOLFIRI-bevacizumab combination treatment resulted in an 89% overall clinical benefit rate and a 44% (four out of nine patients) objective response rate (ORR) as of the ASCO (Free ASCO Whitepaper) data cutoff.
One additional objective response was achieved post ASCO (Free ASCO Whitepaper) reporting (overall ORR of 45% with five of 11 evaluable patients seeing an objective response).
Data continues to demonstrate a ten-fold improvement in ORR with onvansertib-FOLFIRI- bevacizumab combination treatment compared to the current standard-of-care.
Median progression-free survival of >6 months at data cutoff; with six patients remaining on treatment as of the time of the presentation.
Safety and tolerability demonstrated across all onvansertib dose levels evaluated to-date.
Presented new clinical data showing that onvansertib-FOLFIRI-bevacizumab combination therapy led to consistent tumor regression and durable response across KRAS mutation subtypes in patients with KRAS-mutated mCRC at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) annual conference

The newly announced positive results from our ongoing Phase 1b/2 clinical trial of onvansertib in combination with FOLFIRI and Avastin (bevacizumab) for second-line treatment of patients with KRAS-mutated mCRC were featured in Dr. Afsaneh Barzi’s virtual oral presentation at the 2020 AACR (Free AACR Whitepaper) annual conference. The ongoing Phase 1b/2 trial has enrolled 12 patients with responses seen in seven of eight (88%) evaluable patients to-date: three patients exhibiting a partial response (PR), and four patients with stable disease (SD). Levels of circulating tumor DNA (ctDNA) with KRAS mutations in the blood during treatment are used as a predictive biomarker in the trial, with a decrease to non-detectable levels during the first treatment cycle being indicative of subsequent tumor regression and response.

Announced the U.S. Food and Drug Administration’s (FDA) decision to grant Fast Track Designation to onvansertib for second line treatment of KRAS-mutated colorectal cancer

The FDA’s decision to grant Fast Track Designation to onvansertib for the second line treatment of KRAS-mutated mCRC, provides us with the opportunity to seek priority review and accelerated approval in this indication. This designation underscores the urgent need for new treatment options for KRAS-mutated mCRC patients and indicates that the FDA concluded that the investigation of onvansertib, in combination with FOLFIRI/bevacizumab, for second line treatment of patients with KRAS-mutated mCRC, met the criteria for a Fast Track development program.

Announced initiation of Expanded Access Program (EAP) for onvansertib in combination with standard-of-care FOLFIRI and bevacizumab for the treatment of second line KRAS-mutated mCRC

Initiation of the EAP provides patients with a pathway to gain access to treatment with onvansertib outside of our clinical trial.

Acute Myeloid Leukemia (AML) Program:

Presented clinical data further demonstrating the efficacy, durability and safety of onvansertib in patients with difficult-to-treat relapsed/refractory AML at the European Hematology Association (EHA) (Free EHA Whitepaper) annual conference

Final results of our Phase 1b relapsed/refractory AML study, and positive preliminary data from our Phase 2 relapsed/refractory AML study, were presented as a virtual poster at the 2020 EHA (Free EHA Whitepaper) annual conference. Data highlights from the presentation included:

Phase 1b: Seven out of 21 (33%) evaluable patients achieved an objective response, with five (24%) patients achieving a complete response (CR/CRi).
Phase 1b: Among the five patients achieving a CR/CRi, one patient proceeded to transplant and three patients remain on treatment with ongoing durable responses of 6, 12 and 15 months.
Phase 2: Two out of seven (28%) patients completing one cycle of treatment achieved an objective response. One out of seven (14%) had a complete response (CR) and significant decrease in ctDNA, which was found to be highly predictive of clinical response.
Phase 2: Data indicate that onvansertib in combination with decitabine continues to be a safe and well-tolerated treatment regimen.
Corporate Milestones:

$25.1 million in equity investments, warrant exercises and clinical trial funding commitments

Second quarter equity investments and warrant exercises to fund current clinical programs and operations:

$13.5 million equity investment from biotech-focused institutional investors Acorn Bioventures LP and CAM Capital. The financing included common stock, Series E preferred stock and warrants.
$2.5 million equity investment from biotech-focused institutional investor Acorn Bioventures LP. The financing included common stock and warrants.
$1.1 million equity investment from Lincoln Park Capital Fund LLP. The financing included common stock and warrants.
$0.8 million private placement by the Board of Directors and Chief Executive Officer. The company sold common stock at market prices.
$4.9 million in various warrant exercises.
Second quarter clinical trial funding commitments:

$2.3 million commitment from PoC Capital to fund our Phase 2 clinical trial of onvansertib in KRAS-mutated mCRC. The financing included common stock, Series D preferred stock and warrants.
Company name change to Cardiff Oncology, Inc.

On May 8, 2020, we changed our company name from Trovagene, Inc. to Cardiff Oncology, Inc., and our Nasdaq ticker symbol from ‘TROV’ to ‘CRDF.’ The web address for the Cardiff Oncology website is www.cardiffoncology.com.

Appointment of Dr. Mark Erlander as chief executive officer

On May 8, 2020, Mark Erlander, Ph.D., assumed the role of chief executive officer and Thomas Adams, Ph.D., transitioned from chief executive officer and chairman to executive chairman.

Strengthened Board of Directors with the addition of three industry leaders

Shareholders elected three new independent directors to our board of directors; Dr. James Armitage, Dr. Gary Pace and Ms. Lâle White. Each new director brings extensive and relevant experience to the board of Cardiff Oncology.

Second Quarter 2020 Financial Results:

As of June 30, 2020, Cardiff Oncology had approximately $27.8 million in cash and cash equivalents and $2.8 million in clinical trial funding commitments included within stockholders’ equity.

Total operating expenses were approximately $4.1 million for the three months ended June 30, 2020, a decrease of $0.2 million from $4.3 million for the same period in 2019. The decrease in operating expenses is attributed to a decrease in costs associated with clinical programs and outside services, partially offset by an increase in stock-based compensation and staff costs.

Net cash used in operating activities in the second quarter of 2020 was $4.3 million, an increase of $0.9 million from $3.4 million for the same period in 2019. The increase is attributed to the net changes in our operating assets and liabilities.

Research and development expenses decreased by approximately $0.3 million to $2.5 million for the three months ended June 30, 2020, from $2.8 million for the same period in 2019. The decrease in research and development expenses was primarily due to lower expenses associated with clinical programs and outside services.

Selling, general and administrative expenses increased by approximately $0.3 million to $1.7 million for the three months ended June 30, 2020 from $1.4 million for the same period in 2019. The increase is primarily due to an increase in stock-based compensation, staff costs and facilities, off-set by a decrease in outside services.

On August 11, 2020 DiaMedica Therapeutics Inc. (Nasdaq: DMAC), a clinical-stage biopharmaceutical company focused on developing novel treatments for kidney diseases and neurological disorders, reported a business update and financial results for the three and six months ended June 30, 2020 (Press release, DiaMedica, AUG 11, 2020, View Source [SID1234563423]). DiaMedica will host a conference call tomorrow, August 12, 2020, at 7:00 a.m. Central Time to discuss its business update and second quarter financial results.

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Clinical Developments

DM199 for the Treatment of Chronic Kidney Disease

Phase II Clinical Study in CKD Caused by IgA Nephropathy, in African Americans with Hypertension – Enrollment Continues

Initiation of Third Cohort in CKD caused by Type II Diabetes Mellitus

The Phase II REDUX (Latin for restore) trial is a multi-center, open-label investigation of approximately 90 evaluable participants with chronic kidney disease (CKD), who are being enrolled in three cohorts (30 per cohort). The study is being conducted in the United States and a 13th site was added in July 2020.

REDUX targets participants with CKD. Cohort I of the study is focused on non-diabetic, hypertensive African Americans with Stage II or III CKD, a group which is at greater risk for CKD than Caucasians. African Americans who have the APOL1 gene mutation are at an even higher risk. The study is designed to capture the APOL1 gene mutation as an exploratory biomarker in this cohort. Cohort II of the study is focused on participants with IgA Nephropathy (IgAN). Based upon additional data from DiaMedica’s completed ReMEDy study showing significantly improved estimated glomerular flow rate (eGFR) and reduced blood glucose levels, and with a portion of the net proceeds from the recent public offering of common shares, the Company is initiating a third cohort, Cohort III, focused on participants with Type II diabetes mellitus, hypertension and albuminuria.

"The addition of this diabetic cohort is timely in that it leverages our current sites, which also have this patient population," commented Dr. Harry Alcorn, Jr., DiaMedica’s Chief Medical Officer. "We look forward to this cohort expanding our understanding of the potential of DM199 in the treatment of diabetic patients with kidney disease."

In a post hoc analysis of endpoints in the ReMEDy trial, a sub-set of 25 participants with elevated blood glucose levels (>7 mmol/l) and impaired kidney function (eGFR <90) were observed to experience significant (mean +12.7 mL/min, p=0.03) improvement in kidney function as measured by the estimated glomerular filtration rate compared to placebo (mean increase 12.7 mL/min, p=0.03) and a trending reduction in blood glucose levels (mean 2.2 mmol/l) compared to placebo (mean decrease 2.2 mmol/l).

The REDUX study will evaluate two dose levels of DM199 within each cohort. Study participants will receive DM199 by subcutaneous injection twice weekly for 95 days. The primary study endpoints include safety, tolerability, blood pressure, albuminuria and kidney function, which will be evaluated by changes from baseline in eGFR and albuminuria, as measured by the urinary albumin to creatinine ratio (UACR). Secondary endpoints are focused on evaluating the potential for DM199 to positively impact the underlying disease causing each participant’s CKD.

As of August 5, 2020, enrollment in the first two cohorts of the REDUX study was approximately one-third complete. Due to actions implemented to combat the novel strain of the coronavirus (COVID-19) pandemic, the Company has experienced and continues to experience slower than expected enrollment in the REDUX clinical trial. The Company believes this is due to a combination of the reduction or suspension of activities at its clinical study sites as they address staff and patient safety concerns and patient concerns related to visiting clinical study sites. The Company anticipates that the COVID-19 pandemic will likely continue to adversely affect its ability to recruit or enroll subjects and cannot provide any assurance as to when clinical sites will be able to resume enrollment at a normal rate or any guidance at this time as to when it will complete enrollment in the study. The Company added a 13th study site in July 2020 to assist with subject enrollment and will consider additional sites if conditions warrant. While results observed to date in the REDUX study indicate a safety profile consistent with past studies, there is insufficient data at this time for the Company to evaluate or comment upon efficacy.

DM199 for the Treatment of Acute Ischemic Stroke

DM199 Acute Ischemic Stroke Phase II "ReMEDy" Trial – Positive Top-Line Data

DiaMedica previously announced positive top-line results from its ReMEDy trial, a Phase II study assessing the safety, tolerability and therapeutic potential of DM199 in participants suffering from acute ischemic stroke (AIS). Final enrollment was 92 participants. The study met primary safety and tolerability endpoints and there were no DM199-related serious adverse events. In addition, there was also a demonstrated therapeutic effect in participants who received tissue plasminogen activator (tPA) prior to enrollment, but not in participants receiving mechanical thrombectomy prior to enrollment.

DM199 is intended to treat the approximately 90% of AIS patients who do not receive either mechanical thrombectomy or tPA. Treatment for these patients is limited to palliative therapies. When participants treated with mechanical thrombectomy are excluded from the study data set, a positive therapeutic effect was demonstrated. As shown in the table below, participants treated with DM199 (n=25) vs. palliative therapies and/or tPA (n=21), the results showed that 36% of participants receiving DM199 progressed to a full or nearly full recovery at 90 days (National Institutes of Health Stroke Score: 0-1), compared to 14% of participants in the placebo group. This represents a 22% absolute increase in the proportion of participants achieving a full or nearly full recovery. Additionally, subject deaths decreased from 24% in the placebo group to 12% in the active therapy group, a 50% relative reduction.

DiaMedica is currently developing the protocol for a proposed Phase III study of DM199 in the treatment of AIS and preparing a request for a Type B meeting with the U.S. Food and Drug Administration (FDA). The meeting request is expected to be filed shortly and, if the FDA agrees, this meeting would likely take place in the fourth quarter of 2020.

With respect to the overall ReMEDy results, prior to enrollment, 44 of the 91 evaluable patients (48%) received a mechanical thrombectomy, a catheter-based treatment indicated for those who have a large vessel occlusion and can be treated within 6 to 24 hours of the onset of stroke symptoms. While approximately 20% of AIS patients are believed to be eligible for a mechanical thrombectomy, currently only about 5% to 10% receive the treatment due to elapsed time post-stroke or unavailability of the therapy at the hospital where they present. Due to the large volume of participants receiving mechanical thrombectomy prior to enrollment in ReMEDy, and a disproportionate distribution of these participants between the active treatment and placebo groups, DM199 did not produce a therapeutic effect in the overall study analysis.

Recent Public Offering

On August 10, 2020, the Company issued and sold an aggregate of 4,600,000 common shares in a public underwritten offering at a public offering price of $5.00 per share, receiving gross proceeds of $23.0 million, which includes a full exercise by the underwriters of their option to purchase additional shares, and net proceeds of $21.1 million, after deducting the underwriting discount and estimated offering expenses.

Financial Results

Research and development (R&D) expenses decreased to $1.6 million for the three months ended June 30, 2020, down from $1.9 million for the three months ended June 30, 2019, a decrease of $0.3 million. R&D expenses decreased to $3.0 million for the six months ended June 30, 2020, compared to $4.5 million for the six months ended June 30, 2019, a decrease of $1.5 million. The decrease for the six month comparison was due primarily to non-recurring costs of approximately $1.3 million incurred for a new production run of the DM199 drug substance during the prior year period, and a net decrease in year-over-year clinical study costs. The decrease in clinical study costs was due to a combination of the decreased ReMEDy stroke study expenses as it winds down and Phase 1b CKD study costs which study was started and completed in the prior year period. These decreases were partially offset by costs incurred for the REDUX Phase II CKD study initiated late in 2019 and increased non-cash share-based compensation costs.

General and administrative (G&A) expenses were $1.1 million for the three months ended June 30, 2020, up from $867,000 for the three months ended June 30, 2019. G&A expenses increased to $2.1 million for the six months ended June 30, 2020, up $0.4 million, from $1.7 million for the six months ended June 30, 2019. The increase for the six-month comparison was due primarily to increased non-cash share-based compensation costs.

Total other income decreased to $243,000 for the three months ended June 30, 2020, down from $280,000 for the prior year period. Total other income decreased to $231,000 for the six months ended June 30, 2020, compared to $458,000 for the six months ended June 30, 2019. The decrease for the six-month comparison is primarily related to reduced R&D incentives associated with decreased ReMEDy stroke study costs during the six months ended June 30, 2019, partially offset by reduced foreign currency transaction losses.

Balance Sheet and Cash Flow

The Company had cash, cash equivalents and marketable securities of $11.8 million, current liabilities of $1.2 million and working capital of $11.2 million as of June 30, 2020, compared to $7.9 million in cash, cash equivalents and marketable securities, $1.3 million in current liabilities and $7.5 million in working capital as of December 31, 2019. The increases in the Company’s combined cash, cash equivalents and marketable securities and in its working capital are due primarily to the February 2020 public offering of common shares.

Net cash used in operating activities was $3.8 million for the six months ended June 30, 2020, compared to $6.0 million for the six months ended June 30, 2019. The net cash used in each of these periods primarily reflects the net loss for these periods, non-cash charges for stock-based compensation and adjustments for the net effects of changes in operating assets and liabilities.

Conference Call Information

DiaMedica Management will host a conference call to discuss both its second quarter 2020 financial results and the top-line results from its ReMEDy study on Wednesday, August 12, 2020, at 7:00 a.m. Central Time:

Date:

Wednesday, August 12, 2020

Time:

7:00 AM CT / 8:00 AM ET

Web access:

View Source

Conference ID:

7689626

Interested parties may access the conference call by dialing in or listening to the simultaneous webcast. Listeners should log on to the website or dial in 15 minutes prior to the call. All participants on the conference call will be provided with the dial in instructions and a unique passcode once they register. This information will also be sent in an email confirmation. The webcast will remain available for play back on our website, under investor events and presentations, following the earnings call and for 12 months thereafter. A telephonic replay of the conference call will be available until August 13, 2020, by dialing (855) 859-2056 (US Toll Free), (404) 537-3406 (International), replay passcode 7689626.

About DM199

DM199 is a recombinant (synthetic) form of human tissue kallikrein-1 (KLK1). KLK1 is a serine protease (protein) that plays an important role in the regulation of diverse physiological processes including blood flow, inflammation, fibrosis, oxidative stress and neurogenesis via a molecular mechanism that increases production of nitric oxide and prostaglandin. KLK1 deficiency may play a role in multiple vascular and fibrotic diseases such as chronic kidney disease, retinopathy, stroke, vascular dementia, and resistant hypertension where current treatment options are limited or ineffective. DiaMedica is the first company to have developed a recombinant form of the KLK1 protein. The KLK1 protein, produced from porcine pancreas and human urine, has been used to treat patients in Japan, China and Korea for decades. DM199 is currently being studied in patients with chronic kidney disease and patients with acute ischemic stroke.

On August 11, 2020 Sun BioPharma, Inc. (OTCQB: SNBP), a clinical stage biopharmaceutical company developing disruptive therapeutics for the treatment of patients with pancreatic cancer, reported financial results for the quarter ended June 30, 2020 (Press release, Sun BioPharma, AUG 11, 2020, View Source;utm_medium=rss&utm_campaign=sbp-provides-business-update-and-reports-q2-2020-financial-results [SID1234563422]). The second quarter of 2020 was marked by meaningful corporate, financial and clinical progress.

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Highlights

New CEO appointed on July 15, 2020
Enrollment in clinical trial of SBP-101 has resumed, after temporary, Covid-19 related pause
Fast Track designation received for SBP-101
Additional funds raised through sale of equity securities
CEO Appointment
In July, the company appointed of Jennifer K. Simpson, PhD, MSN, CRNP as President and Chief Executive Officer and as a member of the Board of Directors. Dr. Simpson brings more than two decades of public company executive and fundraising experience in oncology drug development and commercialization to the company. Sun BioPharma co-founder Michael T. Cullen, MD, MBA, has continued to serve as Executive Chairman of our Board of Directors.

"I’m excited that we were able to resume enrollment in our clinical trial of SBP-101 in order to keep advancing this program for the patients who need it most," said Jennifer K. Simpson, PhD, MSN, CRNP President & Chief Executive Officer of Sun BioPharma. "The company is well positioned to maximize the opportunity for value of this product candidate for patients, caregivers and investors, and we look forward to completing the design of our Phase 2 development program shortly."

Enrollment Resumed in Ongoing Clinical Trial of SBP-101
In June, Sun BioPharma authorized clinical trial sites to resume enrollment in the expansion cohort of its Phase 1a/b clinical trial of SNBP-101. Enrollment in many clinical trials across the industry had been temporarily paused earlier this year to enable hospitals to prioritize the treatment of patients with COVID-19. This trial, a Phase 1a/1b study of the combination of SBP-101 with gemcitabine and nab-paclitaxel in patients previously untreated for metastatic pancreatic ductal adenocarcinoma (PDA), is being conducted at 6 sites in the United States and Australia.

FDA Fast Track Designation Received for SBP-101
During the second quarter, the company received Fast Track Designation from the U.S. Food and Drug Administration (FDA) for SBP-101 for first-line treatment of patients with metastatic PDA when administered in combination with gemcitabine and nab-paclitaxel. One of FDA’s Expedited Programs for Serious Conditions, Fast Track is a process designed to facilitate the development and potentially expedite the review of drugs intended to treat serious conditions and address unmet medical needs. This designation is expected to enhance Sun BioPharma’s ability to develop SBP-101 as efficiently as possible.

Recent Sales of Common Stock and Warrants Raised $1.7 Million
In May and June, the company sold common stock and warrants in private placements resulting in net proceeds totaling approximately $1.7 million, which the company intends to use primarily to support its ongoing clinical trial. A total of 437,000 shares of common stock were issued in addition to warrants to purchase an equal number of shares of common stock.

Second Quarter ended June 30, 2020 Financial Results

General and administrative expenses increased to $0.7 million in the second quarter of 2020, up from $0.6 million in the second quarter of 2019. The increase in the second quarter is due to higher consulting and legal expense offset in part by lower stock compensation expense.

Research and development expenses decreased to $0.4 million in the second quarter of 2020, down from $0.5 million in the second quarter of 2019. The decrease in the second quarter is due to lower spending on preclinical studies and lower stock compensation expense.

Operating expenses in the second quarter were partially offset by a foreign currency exchange gain on the intercompany receivable balance. In the second quarter of 2019, other expense was primarily interest expense which resulted from the amortization of debt discount on convertible notes sold in 2018 and 2019.

Net loss in the second quarter of 2020 was $0.4 million, or $0.06 per diluted share, compared to a net loss of $2.3 million, or $0.45 per diluted share, in the second quarter of 2019.

Total cash was $2.3 million as of June 30, 2020. Total current assets were $3.3 million and current liabilities were $1.7 million as of the same date.

About SBP-101

SBP-101 is a proprietary polyamine analogue designed to induce polyamine metabolic inhibition (PMI) by exploiting an observed high affinity of the compound for the exocrine pancreas and pancreatic ductal adenocarcinoma. The molecule has shown signals of tumor growth inhibition in clinical studies of US and Australian metastatic pancreatic cancer patients, suggesting complementary activity with an existing FDA-approved chemotherapy regimen. In clinical studies to date, SBP-101 has not shown exacerbation of the typical chemotherapy-related adverse events of bone marrow suppression and peripheral neuropathy. The safety data and PMI profile observed in Sun BioPharma’s current clinical trial provides support for continued evaluation of the compound in a randomized clinical trial. For more information, please visit View Source

On August 11, 2020 Fennec Pharmaceuticals Inc., a specialty pharmaceutical company, reported that it received a Complete Response Letter (CRL) on August 10, 2020 from the U.S. Food and Drug Administration (FDA) regarding its New Drug Application (NDA) for PEDMARKTM (a unique formulation of sodium thiosulfate), for intravenous administration for the prevention of ototoxicity associated with cisplatin chemotherapy in pediatric patients ≥1 month to 18 years of age with localized, non-metastatic, solid tumors (Press release, Fennec Pharmaceuticals, AUG 11, 2020, View Source [SID1234563421]).

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According to the CRL, after recent completion of a pre-approval inspection of the manufacturing facility of our drug product manufacturer, the FDA identified deficiencies resulting in a Form 483, which is a list of conditions or practices that are required to be resolved prior to the approval of PEDMARKTM. The Company plans to request a Type A meeting to discuss the issues and other matters that were described in the CRL pertaining to the steps required for the resubmission of the NDA for PEDMARKTM. Importantly, no clinical safety or efficacy issues were identified during the review and there is no requirement for further clinical data.

"We are steadfast in our commitment to reducing the risk of life-long hearing loss for children receiving cisplatin chemotherapy who currently have no approved therapies for this devastating condition," said Rosty Raykov, chief executive officer of Fennec. "We will work closely with our manufacturer and the FDA to fully address the issues raised in the letter as expeditiously as possible."

The Company has existing cash, which totaled approximately $38.7 million as of June 30, 2020.

Conference Call and Webcast

Fennec will host a conference call and webcast on Tuesday, August 11, 2020, at 8:30 a.m. ET. The conference call can be accessed by dialing (833) 614-1446 for domestic callers or (918) 922-6512 for international callers. Please provide the operator with the conference ID 7791698 to join the conference call.

About PEDMARK (A unique formulation of sodium thiosulfate (STS))

Cisplatin and other platinum compounds are essential chemotherapeutic agents for many pediatric malignancies. Unfortunately, platinum-based therapies cause ototoxicity, or hearing loss, which is permanent, irreversible and is particularly harmful to the survivors of pediatric cancer.

In the U.S. and Europe, it is estimated annually that over 10,000 children may receive platinum-based chemotherapy. The incidence of ototoxicity depends upon the dose and duration of chemotherapy, and many of these children require lifelong hearing aids. There is currently no established preventive agent for this type of hearing loss and only expensive, technically difficult and sub-optimal cochlear (inner ear) implants have been shown to provide some benefit. Infants and young children that suffer ototoxicity at critical stages of development lack speech language development and literacy, and older children and adolescents lack social-emotional development and educational achievement.

PEDMARK has been studied by cooperative groups in two Phase 3 clinical studies of survival and reduction of ototoxicity, The Clinical Oncology Group Protocol ACCL0431 and SIOPEL 6. Both studies have been completed. The COG ACCL0431 protocol enrolled one of five childhood cancers typically treated with intensive cisplatin therapy for localized and disseminated disease, including newly diagnosed hepatoblastoma, germ cell tumor, osteosarcoma, neuroblastoma, and medulloblastoma. SIOPEL 6 enrolled only hepatoblastoma patients with localized tumors.

The Marketing Authorization Application (MAA) for sodium thiosulfate (tradename PEDMARQSI) is currently under evaluation by the European Medicines Agency (EMA). PEDMARK has received Breakthrough Therapy and Fast Track Designation by the FDA in March 2018.

On August 11, 2020 Elios Therapeutics, a biopharmaceutical company developing innovative personalized therapeutic cancer vaccines, reported final data from a prospective, randomized, double-blind, placebo-controlled Phase IIb clinical trial evaluating adjuvant use of its personalized tumor lysate, particle-loaded, dendritic cell (TLPLDC) vaccine in patients with Stage III or Stage IV melanoma at high risk of recurrence following complete surgical resection (Press release, Orbis Health Solutions, AUG 11, 2020, View Source [SID1234563420]).

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"We now have long-term data demonstrating that use of the TLPLDC vaccine for the adjuvant treatment of high-risk melanoma correlates with a 93 percent increase in patients alive at three years without their disease returning. This trial also significantly improves our understanding of the optimal method of vaccine production," said Buddy Long, chief executive officer of Elios Therapeutics. "These new data, combined with the doubled rate of disease-free survival among patients treated with the vaccine and standard of care checkpoint inhibitors, further strengthen our confidence that the personalized TLPLDC vaccine provides a clinically meaningful benefit for people with high-risk melanoma. We look forward to advancing this vaccine with a registrational Phase III trial that will move us one step closer to bringing this important treatment to patients as soon as possible."

The TLPLDC vaccine is a personalized treatment that is created using a patient’s own blood and tumor cells. Samples are collected at resection, frozen, and sent to the lab where they are used to create autologous tumor lysate, which is loaded into yeast cell wall particles. This combination is then introduced to the patient’s dendritic cells, leading to the creation of the final TLPLDC vaccine. The time from resection to injection of the vaccine takes approximately three weeks.

The vaccine has been studied in a large randomized Phase IIb trial, and the newly reported data is from the pre-specified 36-month disease-free survival (DFS) and overall survival (OS) assessment by vaccine formulation, stage, and checkpoint inhibition. The analysis included all randomized patients in an intent-to-treat (ITT) analysis. Two versions of the vaccine, one produced by isolating dendritic cells (DCs) from 120 mL of blood (vaccine-A) and one with DCs isolated after a single injection of filgrastim followed by 50-70 mL of blood (vaccine-B), were tested in 144 participants who were randomized to receive either version of the vaccine or placebo to prevent recurrence.

A key finding showed that treatment with vaccine-B resulted in clinical outcomes similar to placebo. Producing the vaccine with filgrastim was intended to increase white blood cell and dendritic cell counts, requiring less blood to be drawn from patients to create the vaccine. While the use of filgrastim increased DC production, it takes only 72-hours to create the vaccine which was not enough time for the DCs to mature, rendering vaccine-B ineffective.

Importantly, vaccine-A, when compared to vaccine-B and placebo, resulted in a statistically significant improvement in 36-month DFS (51.8% vs. 23.4% vs 27.1%, respectively; p=0.027) and OS (92.9% vs. 62.8% vs 70.3%, respectively; p=0.022) in the ITT population.

Furthermore, the DFS improvement with vaccine-A was seen across both Stage III (49.7% vs. 29.4%; p=0.066) and IV (68.6% vs. 9.4%; p=0.0582) patients. Importantly, the addition of vaccine-A to current standard of care checkpoint inhibitors led to a statistically significant increase in 36-month DFS in the ITT population compared to treatment with checkpoint inhibitors alone (48.5% vs. 24.1%; p=0.039). As previously reported, treatment with the vaccine was well-tolerated with 34.7 percent of patients experiencing a treatment-related adverse event, and >90% being grades 1 or 2.

"To demonstrate a long-term survival benefit with low toxicity in a therapeutic is what we hope for in every clinical trial. Achieving this with an aggressive disease like melanoma offers great promise for patients," said Mark B. Faries, M.D., co-director of the Melanoma Program and head of Surgical Oncology at Cedars-Sinai at The Angeles Clinic and Research Institute, and principal investigator of the study. "With data showing a two-fold increase in disease-free survival with the vaccine alone and in combination with checkpoint inhibitors, we hope to one day change the narrative for people with melanoma – turning this disease into a chronic condition that can be treated and managed over time."

About Melanoma
Melanoma is more likely to grow and spread than other types of skin cancer. When diagnosed and treated at an early stage, melanoma has a high cure rate, however patients with later stages of the disease carry a high risk for melanoma recurrence because some melanoma cells can remain in the body, even after surgery. In the U.S, the incidence of melanoma has increased over the past decades, with 91,270 estimated new cases and 9,320 related deaths in 2018^1.

About the Phase IIb TLPLDC Study
This Phase IIb study is a prospective, randomized, double-blind, placebo-controlled trial designed to evaluate the safety and efficacy of the TLPLDC (tumor lysate, particle-loaded, dendritic cell) vaccine in patients with resected Stage III and IV melanoma. The primary endpoint of the trial is two-year disease-free survival (DFS), and the secondary endpoint is three-year DFS and overall survival (OS).

In the study, 144 participants were randomized to receive either the vaccine or placebo to prevent recurrence. TLPLDC or placebo vaccines were initiated within three months of completion of standard of care (SoC) therapies and were given at 0, 1, 2, 6, 12, and 18 months. The protocol was amended to allow concurrent checkpoint inhibitor therapy once approved for the adjuvant setting. Study participants were followed for recurrence per SoC. The primary efficacy analysis was performed on the intent-to-treat (ITT) and the per treatment (PT) populations as co-primary analyses given the high early recurrence rate often seen in patients with advanced melanoma. Secondary endpoints include 36-month DFS and overall survival (OS) which will be compared between the vaccinated and control groups as well as by vaccine formulation.

About TLPLDC
The TLPLDC (tumor lysate, particle-loaded, dendritic cell) vaccine is a unique type of immunotherapy, both in how it is made and how it is delivered. The vaccine is personalized, meaning it is made from a patient’s tumor and blood. Every patient’s tumor has a unique antigenic profile unlike any other, and dendritic cells found in the blood are the most potent antigen-presenting cells in the body. Once TLPLDC is administered, it delivers the patient’s complete repertoire of tumor antigens to the immune system, creating a dual innate and adaptive immune response, activating fighter T cells, and triggering the immune system to recognize, and seek out and destroy any cells containing the antigens and specific mutations from their tumor.

Historically, autologous cancer vaccines have been rather onerous to develop, sometimes taking months between the tumor biopsy and administration. Elios has simplified the process so the time from resection to injection is approximately two weeks. This makes the vaccine highly feasible and will ultimately be easy for community and academic oncologists to adopt into their practices.

The TLPLDC vaccine is currently being studied as a monotherapy and in combination with standard-of-care checkpoint inhibitor therapies in a Phase IIb clinical trial for the treatment of late-stage melanoma at leading academic cancer centers in the United States.