On December 9, 2021 Totus Medicines, a drug discovery company using breakthrough chemical biology to make the entire human genome druggable, reported its revolutionary drug program targeting PI3Kα, the most commonly mutated cancer oncogene (Press release, Totus Medicines, DEC 9, 2021, View Source [SID1234596658]). The company also announced a $40 million Series A funding round led by investors DCVC Bio and Northpond Ventures and supported by Camford Capital with original seed funding from Social Impact Capital. The Series A financing will be used to expand and scale Totus Medicines’ proprietary drug discovery platform and advance the company’s lead program into the clinic.

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Totus Medicines’ TOS-358 drug program targets the PI3Kα mutation, which impacts more than 500,000 people in the U.S. every year and drives a significant percentage of breast, colon, lung, bladder, stomach, and other cancers. The pharmaceutical industry has spent decades and billions of dollars attempting to target PI3Kα, and current inhibitors only achieve moderate success in <10% of patients with PI3Kα-mutant cancers.

In just 18 months, Totus has used its proprietary drug discovery platform to develop TOS-358, which shows strong preclinical efficacy across PI3Kα-mutant tumor types where current PI3Kα inhibitors show weak to no efficacy. In patient-derived mouse xenograft models, TOS-358 induces tumor regressions across breast, colon, lung, stomach, and other models, while current inhibitors show mild effects. Totus Medicines will begin clinical trials for the TOS-358 drug program in the second half of 2022.

"Our drug discovery platform is capable of creating treatments for previously untreatable diseases," said Neil Dhawan, Ph.D., co-founder and CEO of Totus Medicines. "We are drugging undruggable targets at scale, moving us closer to a world where every physician and every patient can look forward to effective treatments for the most devastating illnesses. The TOS-358 drug program is a crowning achievement in that mission, and we look forward to advancing the program—and many others—into the clinic."

Totus Medicines’ platform uses proprietary molecular tags that track drug binding in individual cells to screen billions of drug molecules across thousands of genes in parallel. By combining this approach with breakthrough machine learning techniques, the company has developed the next generation of cellular analysis. Continuously learning and adapting, the Totus platform is more effective, less costly, and thousands of times faster than legacy drug discovery methods, enabling the rapid translation of therapies to patients. Totus aims to screen two billion compounds across the human genome within the next two years to unlock precise, effective drugs across hundreds of high-value drug targets.

"The Series A financing will allow us to refine and grow the Totus platform to find new treatments for previously untreatable diseases—faster and more successfully than has ever been possible," said Jason Pontin, a Partner at DCVC, and a board member and co-founder of Totus Medicines. "The promise of Totus Medicines is that doctors can offer life-changing medicines to patients who would otherwise have little hope."

On December 9, 2021 Clovis Oncology, Inc. (NASDAQ: CLVS) reported that presentation by Andrew D. Simmons, Ph.D., Clovis’ Senior Vice President, Translational Medicine, at the 3rd Targeted Radiopharmaceuticals Summit being held virtually December 7-9, 2021 (Press release, Clovis Oncology, DEC 9, 2021, View Source [SID1234596657]). Dr. Simmons’ presentation, titled "Innovations in Peptide Targeted Radionuclide Therapies (PTRT) to Target Fibroblast Activation Protein (FAP) in Solid Tumors", reviews the Company’s preclinical data and describes the Phase 1/2 study currently enrolling for its targeted radiotherapy candidate FAP-2286, the first PTRT and imaging agent targeting FAP to enter clinical development and the lead candidate in Clovis Oncology’s targeted radionuclide therapy (TRT) development program.

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"Clinician enthusiasm for the potential of targeted radiopharmaceuticals, and in particular, FAP as a target, continues to increase, and we are committed to becoming a leader in this emerging field," said Patrick J. Mahaffy, President and CEO of Clovis Oncology. "We look forward to sharing initial data from the ongoing Phase 1 LuMIERE study of our first targeted radiotherapy candidate FAP-2286, anticipated in 2022."

Following Dr. Simmons’ presentation at 9:35am Eastern time, his slide presentation can be found at View Source with other recent Clovis-sponsored presentations, posters and supplemental information. For more information about FAP-2286, targeted radionuclide therapy, or Clovis’ TRT development program, please visit targetedradiotherapy.com.

About FAP-2286

FAP-2286 is a clinical candidate under investigation as a peptide-targeted radionuclide therapy (PTRT) and imaging agent targeting fibroblast activation protein (FAP). FAP-2286 consists of two functional elements; a targeting peptide that binds to FAP and a site that can be used to attach radioactive isotopes for imaging and therapeutic use. High FAP expression has been shown in pancreatic ductal adenocarcinoma, salivary gland, mesothelioma, colon, bladder, sarcoma, squamous non-small cell lung, squamous head and neck cancers, and cancers of unknown primary. High FAP expression was detected in both primary and metastatic tumor samples and was independent of tumor stage or grade. Clovis holds US and global rights for FAP-2286 excluding Europe, Russia, Turkey, and Israel.

FAP-2286 is an unlicensed medical product.

About Targeted Radionuclide Therapy

Targeted radionuclide therapy is an emerging class of cancer therapeutics, which seeks to deliver radiation directly to the tumor while minimizing delivery of radiation to normal tissue. Targeted radionuclides are created by linking radioactive isotopes, also known as radionuclides, to targeting molecules (e.g., peptides, antibodies, small molecules) that can bind specifically to tumor cells or other cells in the tumor environment. Based on the radioactive isotope selected, the resulting agent can be used to image and/or treat certain types of cancer. Agents that can be adapted for both therapeutic and imaging use are known as "theranostics." Clovis, together with licensing partner 3B Pharmaceuticals, is developing a pipeline of novel, targeted radiotherapies for cancer treatment and imaging, including its lead candidate, FAP-2286, an investigational peptide-targeted radionuclide therapeutic (PTRT) and imaging agent, as well as three additional discovery-stage compounds.

About the LuMIERE Clinical Study

LuMIERE is a Phase 1/2 study evaluating FAP-2286 as a peptide-targeted radionuclide therapy (PTRT) targeting fibroblast activation protein, or FAP, in patients with advanced solid tumors (NCT04939610). The Phase 1 portion of the LuMIERE study is evaluating the safety of the investigational therapeutic agent and will identify the recommended Phase 2 dose and schedule of lutetium-177 labeled FAP-2286 (177Lu-FAP-2286). FAP-2286 labeled with gallium-68 (68Ga-FAP-2286) will be utilized as an investigational imaging agent to identify patients with FAP-positive tumors appropriate for treatment with the therapeutic agent. Once the Phase 2 dose is determined, Phase 2 expansion cohorts are planned in multiple tumor types.

On December 9, 2021 AstraZeneca reported that New results from the DESTINY-Breast03 Phase III trial showed that Enhertu (trastuzumab deruxtecan) demonstrated a higher progression-free survival (PFS) and objective response rate (ORR) in pre-specified patient subgroups compared to trastuzumab emtansine (T-DM1) in patients with HER2-positive unresectable and/or metastatic breast cancer previously treated with trastuzumab and a taxane (Press release, AstraZeneca, DEC 9, 2021, View Source [SID1234596655]).

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Enhertu is a HER2-directed antibody drug conjugate (ADC) being jointly developed by AstraZeneca and Daiichi Sankyo Company, Limited (hereafter, Daiichi Sankyo).

A similar PFS and ORR benefit was observed in exploratory analyses in patients defined by stable brain metastases, hormone receptor status, number of prior lines of therapy, prior pertuzumab treatment, or status of visceral metastasis. Results were presented in an oral presentation at the 2021 San Antonio Breast Cancer Symposium (SABCS).

In patients with stable brain metastases at baseline, treatment with Enhertu resulted in higher PFS compared to T-DM1 (PFS by blinded independent central review (BICR) hazard ratio [HR] 0.25; 95% confidence interval [CI] 0.13-0.45). Additionally, in this subgroup, Enhertu improved PFS to a median of 15 months versus 3 months for T-DM1.

Sara Hurvitz, MD, FACP, medical oncologist, professor of medicine, and director of the Breast Cancer Clinical Trials Program in the division of hematology-oncology at the David Geffen School of Medicine at UCLA, and medical director for the Clinical Research Unit at the UCLA Jonsson Comprehensive Cancer Center in Santa Monica, CA, said: "The main goals in the treatment of HER2-positive metastatic breast cancer, including those with stable brain metastases are to improve symptoms, stabilise or reduce the tumour size and improve overall survival. The higher progression-free survival seen in DESTINY-Breast03 in the subgroup of patients with stable brain metastases are encouraging, and underscores the excitement around another potential treatment option for patients who have experienced disease progression on currently available therapies."

Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said: "More treatment options are needed to delay progression and extend survival for patients with HER2-positive metastatic breast cancer who develop brain metastases. These additional analyses from DESTINY-Breast03 reinforce the potential of Enhertu with similar benefits in the different subgroups."

Ken Takeshita, Global Head, R&D, Daiichi Sankyo, said: "These additional analyses from DESTINY-Breast03 continue to demonstrate the benefit of Enhertu compared to T-DM1 in patient subgroups, including 15-month progression-free survival in those with stable brain metastases, illustrating the potential of this treatment to become the new standard of care in patients with previously treated HER2-positive metastatic breast cancer. These data will support our ongoing conversations with global health authorities to realise our commitment to bring Enhertu to patients with previously treated HER2-positive breast cancer earlier in the metastatic setting."

Between 30 to 50% of patients with HER2-positive metastatic breast cancer will develop brain metastases, and while increased availability of HER2 therapies has improved systemic disease control, prognosis following the development of brain metastases remains poor.1-5

Confirmed ORR for patients with stable brain metastases at baseline was 67.4% with Enhertu versus 20.5% with T-DM1. A retrospective, non-prespecified evaluation of intracranial response among patients with stable brain metastases who received scans at baseline provided preliminary evidence that treatment with Enhertu is associated with intracranial tumour response and reduction in Central Nervous System disease with 10 (27.8%) complete responses (CR) and 13 (36.1%) partial responses (PR) compared to one (2.8%) CR and 11 (30.6%) PRs in those treated with T-DM1.

Summary of DESTINY-Breast03 subgroup analyses

Summary of DESTINY-Breast03 subgroup analyses table
CI, confidence interval; HR, hazard ratio; PFS, progression-free survival; NE, not estimable; ORR, objective response rate
a Absolute ORR Difference, % [Enhertu-T-DM1]
b Patients with rapid progression on (neo)adjuvant therapy were included. Line of therapy does not include endocrine therapy.

The safety profile of the most common adverse events with Enhertu in DESTINY-Breast03 remains consistent with previous clinical trials of Enhertu in breast cancer with no new safety concerns identified. Adjudicated drug-related interstitial lung disease or pneumonitis was reported in 27 patients (10.5%) treated with Enhertu and five patients (1.9%) treated with T-DM1 overall, with no Grade 4 or 5 events.

Based on the primary results of DESTINY-Breast03, Enhertu received its fourth Breakthrough Therapy Designation (BTD) in the US for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received one or more prior anti-HER2-based regimens in September 2021.

Enhertu is approved for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2-based regimens in more than 30 countries based on the results from the DESTINY-Breast01 trial.

Enhertu is being further assessed in a comprehensive clinical development programme evaluating efficacy and safety across multiple HER2-targetable cancers, including breast, gastric, lung and colorectal cancers.

Notes

DESTINY-Breast03
DESTINY-Breast03 is a global head-to-head, randomised, open-label, registrational Phase III trial evaluating the safety and efficacy of Enhertu (5.4mg/kg) versus T-DM1 in patients with HER2-positive unresectable and/or metastatic breast cancer previously treated with trastuzumab and a taxane.

The primary efficacy endpoint of DESTINY-Breast03 is PFS based on blinded independent central review. Secondary efficacy endpoints include overall survival, objective response rate, duration of response, PFS based on investigator assessment and safety.

DESTINY-Breast03 enrolled approximately 500 patients at multiple sites in Asia, Europe, North America, Oceania and South America. For more information about the trial, visit ClinicalTrials.gov.

HER2-positive breast cancer
Breast cancer remains the most common cancer and is one of the leading causes of cancer-related deaths in women worldwide.6 More than two million patients with breast cancer were diagnosed in 2020, resulting in nearly 685,000 deaths globally.6 Approximately one in five cases of breast cancer are considered HER2-positive.7

HER2 is a tyrosine kinase receptor growth-promoting protein expressed on the surface of many types of tumours, including breast, gastric, lung and colorectal cancers.8 HER2 protein overexpression may occur as a result of HER2 gene amplification and is often associated with aggressive disease and a poor prognosis in breast cancer.9

Despite initial treatment with trastuzumab and a taxane, patients with HER2-positive metastatic breast cancer will often experience disease progression.1 Additionally, it is estimated that 30 to 50% of patients will develop brain metastases, and while increased availability of HER2 therapies has improved systemic disease control, prognosis following development of brain metastases remains poor.1-5 More treatment options are needed to further delay progression and extend survival.1-4

Enhertu
Enhertu is a HER2-directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC technology, Enhertu is the lead ADC in the oncology portfolio of Daiichi Sankyo and the most advanced programme in AstraZeneca’s ADC scientific platform. Enhertu consists of a HER2 monoclonal antibody attached to a topoisomerase I inhibitor payload, an exatecan derivative, via a stable tetrapeptide-based cleavable linker.

Enhertu (5.4 mg/kg) is approved in more than 30 countries for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2-based regimens in the metastatic setting based on the results from the DESTINY-Breast01 trial.

Enhertu (6.4 mg/kg) is also approved in several countries for the treatment of adult patients with locally advanced or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma who have received a prior trastuzumab-based regimen based on the results from the DESTINY-Gastric01 trial.

A Type II Variation is currently under review by the European Medicines Agency (EMA) for the treatment of adult patients with locally advanced or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma who have received a prior anti-HER2-based regimen.

Enhertu development programme
A comprehensive development programme is underway globally, evaluating the efficacy and safety of Enhertu monotherapy across multiple HER2-targetable cancers, including breast, gastric, lung and colorectal cancers. Trials in combination with other anticancer treatments, such as immunotherapy, are also underway.

Enhertu was highlighted in the Clinical Cancer Advances 2021 report as one of two significant advancements in the "ASCO Clinical Advance of the Year: Molecular Profiling Driving Progress in GI Cancers," based on data from both the DESTINY-CRC01 and DESTINY-Gastric01 trials, as well as one of the targeted therapy advances of the year in non-small cell lung cancer (NSCLC), based on the interim results of the HER2-mutated cohort of the DESTINY-Lung01 trial.

Enhertu received its fourth BTD in the US, which was for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received one or more prior anti-HER2-based regimens.

Daiichi Sankyo collaboration
Daiichi Sankyo and AstraZeneca entered into a global collaboration to jointly develop and commercialise Enhertu (a HER2-directed ADC) in March 2019, and datopotamab deruxtecan (DS-1062; a TROP2-directed ADC) in July 2020, except in Japan where Daiichi Sankyo maintains exclusive rights. Daiichi Sankyo is responsible for manufacturing and supply of Enhertu and datopotamab deruxtecan.

AstraZeneca in breast cancer
Driven by a growing understanding of breast cancer biology, AstraZeneca is starting to challenge, and redefine, the current clinical paradigm for how breast cancer is classified and treated to deliver even more effective treatments to patients in need – with the bold ambition to one day eliminate breast cancer as a cause of death.

AstraZeneca has a comprehensive portfolio of approved and promising compounds in development that leverage different mechanisms of action to address the biologically diverse breast cancer tumour environment. AstraZeneca aims to continue to transform outcomes for HR-positive breast cancer with foundational medicines Faslodex (fulvestrant) and Zoladex (goserelin) and investigational agents next-generation oral SERD and camizestrant.

PARP inhibitor Lynparza (olaparib) is a targeted treatment option for metastatic breast cancer patients with an inherited BRCA mutation. AstraZeneca with MSD (Merck & Co., Inc. in the US and Canada) continue to research Lynparza in metastatic breast cancer patients with an inherited BRCA mutation and are exploring new opportunities to treat these patients earlier in their disease.

Building on the first approval of Enhertu, a HER2-directed ADC, in previously treated HER2-positive metastatic breast cancer, AstraZeneca and Daiichi Sankyo are exploring its potential in earlier lines of treatment and in new breast cancer settings.

To bring much needed treatment options to patients with triple-negative breast cancer, an aggressive form of breast cancer, AstraZeneca is testing immunotherapy Imfinzi (durvalumab) in combination with other oncology medicines, including Lynparza and Enhertu, evaluating the potential of AKT kinase inhibitor, capivasertib, in combination with chemotherapy, and collaborating with Daiichi Sankyo to explore the potential of TROP2-directed ADC, datopotamab deruxtecan.

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

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

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

On December 9, 2021 Aprea Therapeutics, Inc. (Nasdaq: APRE), a biopharmaceutical company focused on developing and commercializing novel cancer therapeutics that reactivate the mutant tumor suppressor protein, p53, reported that the U.S. Food and Drug Administration (FDA) has removed the full clinical hold on the Company’s clinical trial evaluating the combination of its lead compound, eprenetapopt, with acalabrutinib or with venetoclax and rituximab in lymphoid malignancies (Press release, Aprea, DEC 9, 2021, View Source [SID1234596654]).

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"We are pleased to have addressed the FDA’s concerns and receive clearance to proceed with future clinical study of eprenetapopt in non-Hodgkin’s lymphomas," said Eyal Attar, M.D., Chief Medical Officer of Aprea Therapeutics. "We look forward to continued evaluation of eprenetapopt as a therapeutic option for these patients with unmet medical need."

On December 9, 2021 Applied DNA Sciences, Inc. (NASDAQ: APDN) (the "Company"), a leader in Polymerase Chain Reaction (PCR)-based DNA manufacturing and nucleic acid-based technologies, reported consolidated financial results for the full fiscal year and quarter ended September 30, 2021 (Press release, Applied DNA Sciences, DEC 9, 2021, View Source [SID1234596653]).

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"We are pleased to report a fourth consecutive quarter of year-over-year revenue growth in the fourth quarter and record revenues for the fiscal year, both of which are the result of our decision to enter the COVID-19 testing and assay manufacturing markets and leverage our expertise in PCR refined in our Industrial DNA and LinearDNA businesses," said Dr. James A. Hayward, president and CEO of Applied DNA. "COVID-19-related revenues in the fiscal year were driven by the establishment of ADCL, our clinical laboratory subsidiary, to meet the need for population-scale COVID-19 testing, as well as from sales of our Linea 1.0 COVID-19 Assay Kit and testing consumables. Momentum in COVID-19 testing client acquisition, especially in the second half of the fiscal year, supported our continued investment in ADCL that is now largely complete. We recorded strong year-over-year quarterly revenue comparisons that nevertheless fell short of a key client’s projections due to the combination of increased vaccination rates and vaccine mandates. Average weekly testing levels remain in flux but are on an uptrend: new clients are onboarding in FQ1; the key client’s testing needs have increased since Thanksgiving to include the random testing of vaccinated individuals.

"We were also pleased to see the re-emergence of demand for Industrial DNA from the textile industry and repeat and new orders for LinearDNA in the second half of the fiscal year," continued Dr. Hayward. "The pandemic has impacted demand trends; nevertheless, we believe our textiles practice has gained the attention of global apparel and footwear brands seeking to reprioritize their post-pandemic supply chains towards sustainability, brand protection, and traceability. At LineaRx, vaccine development against COVID-19 has put a large spotlight on nucleic acid therapies, so much so that plasmid manufacturers are projecting long lead times with growing capital and labor costs that are incenting developers to seek an alternative to plasmid DNA-based manufacture. With both factors playing to LinearDNA’s strengths, we believe a window is opening for a disruptive force in the market for therapeutic DNA and particularly as we believe we will generate compelling data from our clinical veterinary trials."

Concluded Dr. Hayward, "In fiscal 2022, the emergence of a new SARS-CoV-2 variant of concern, the unpredictable trajectory of the virus’ mutations, asymmetric vaccine distribution, and potentially waning effectiveness of vaccines, we believe, keep testing on the front lines of the global battle against the virus. Our COVID-19 diagnostic development plan and go-to-market strategy are aligned with our capacity to conduct population-scale testing to meet the evolving demands of current and prospective customers. We are progressing a dual-COVID-19/influenza test and an at-home sample collection system, advancing our Linea SARS-CoV-2 Mutation Panel EUA request, and recently submitted our Linea 2.0 COVID-19 Assay Kit, a new N and E gene-based test for COVID-19 that we believe is well suited to serve our future testing needs as new variants continue to emerge, to the New York State Department of Health for its review as a laboratory developed test. In the non-COVID-19 arena, we are leveraging our deep scientific bench to explore new areas of cutting edge molecular testing that will further leverage our investment in ADCL.

"We are also prepared to capitalize on opportunities cultivated in fiscal 2021 in Industrial DNA and the therapeutic application of LinearDNA. In fiscal 2022 our textiles practice is focused on commercial-scale trials and certain scale-up programs. With LinearDNA, we believe our roadmap to an initial cGMP production capacity is ideally timed given the biotech industry’s increasing investments in cell and gene therapies and nucleic acid vaccines and through valuable third-party validation of the benefits of LinearDNA. We intend to continue to pursue the use of LinearDNA for veterinary therapeutics. In addition, we are closing in on a potentially first-in-human clinical trial opportunity with one of our international customers.""

Fiscal Fourth Quarter 2021 Financial Highlights:

Revenues increased 868% for the fourth quarter of fiscal 2021 to $3.0 million, compared with $314 thousand reported in the same period of the prior fiscal year and increased 79% from $1.7 million for the third quarter of fiscal 2021. The increase in revenues year-over-year was due primarily to an increase in clinical laboratory service revenues of $1.6 million and an increase of $1.0 million in product revenues. Clinical laboratory service revenues represent the revenue from our safeCircle COVID-19 testing and is now presented as a separate revenue line item on the statement of operations. The increase in product revenue was mainly attributable to an increase in sales of DNA concentrate of approximately $810 thousand to protect a textile supply chain.
Total operating expenses increased to $5.6 million for the fourth fiscal quarter of 2021, compared with $4.2 million in the prior fiscal year’s fourth fiscal quarter The year-over-year increase is primarily attributable to an impairment charge of $822 thousand for the write-off of goodwill and the remaining net book value of intangible assets. To a lesser extent the increase was attributable to an accrued bonus, which was subsequently paid by the issuance of stock options, as well as an increase in depreciation and amortization expense of $218 thousand.
Net loss applicable to common stockholders for the quarter ended September 30, 2021, was $4.5 million, or $0.60 per share, compared with a net loss of $4.1 million, or $0.82 per share, for the quarter ended September 30, 2020.
Excluding non-cash expenses, Adjusted EBITDA was negative $3.3 million and a negative $3.8 million for the quarters ended September 30, 2021, and 2020, respectively. See below for information regarding non-GAAP measures.
Cash and cash equivalents stood at $6.6 million on September 30, 2021, compared to $7.8 million as of September 30, 2020.
Fiscal Year 2021 Financial Highlights:

Revenues increased 367% for the fiscal year ended September 30, 2021, to $9.0 million, compared with $1.9 million reported in the prior fiscal year. The increase in revenues year over year was due primarily to an increase in clinical laboratory service revenues of approximately $4.7 million and an increase of $2.7 million in product revenues. The increase in clinical laboratory service revenue was from revenues derived from safeCircle. The increase in product revenue was mainly attributable to an increase in sales of our Linea 1.0 assay. Further increases include approximately $810 thousand in Textiles related to the shipment of DNA concentrate to protect a textile supply chain.
Total operating expenses increased to $18.0 million for fiscal 2021, compared with $13.6 million in the prior fiscal year. The increase is primarily related to an increase in stock-based compensation expense of $667 thousand relating to officer and employee stock option grants that vested immediately and an increase in payroll of approximately $1.1 million. The increase also relates to increases in research and development expenses of $444 thousand and depreciation and amortization of $559 thousand.
Net loss applicable to common stockholders for the fiscal year ended September 30, 2021, was $14.3 million, or $2.07 per share, compared with a net loss of $13.0 million, or $3.32 per share, for fiscal 2020.
Excluding non-cash expenses, Adjusted EBITDA was negative $10.0 million for the fiscal year ended September 30, 2021, compared to negative $11.6 million for the prior fiscal year. See below for information regarding non-GAAP measures.
Fourth Quarter and Full Year Fiscal 2021 Conference Call Information
The Company will hold a conference call and webcast to discuss its fourth quarter and fiscal full year 2021 financial results on Thursday, December 9, 2021, at 4:30 PM ET. To participate on the conference call, please follow the instructions below. While every attempt will be made to answer investors’ questions on the Q&A portion of the call, not all questions may be answered.

Telephonic replay (available 1 hour following the conclusion of the live call through December 19, 2021):

Participant Toll Free: 1-877-344-7529
Participant Toll: 1-412-317-0088
Participant Passcode: 10161912
The webcast and accompanying PowerPoint presentation will be archived on the ‘Company Events’ sub-page of the Company’s Investor Relations website

Information about Non-GAAP Financial Measures
As used herein, "GAAP" refers to accounting principles generally accepted in the United States of America. To supplement our condensed consolidated financial statements prepared and presented in accordance with GAAP, this earnings release includes Adjusted EBITDA, which is a non-GAAP financial measure as defined in Rule 101 of Regulation G promulgated by the Securities and Exchange Commission. Generally, a non-GAAP financial measure is a numerical measure of a company’s historical or future performance, financial position, or cash flows that either excludes or includes amounts that are not normally excluded or included in the most directly comparable measure calculated and presented in accordance with GAAP. The presentation of this non-GAAP financial information is not intended to be considered in isolation or as a substitute for, or superior to, the financial information presented in accordance with GAAP. We use this non-GAAP financial measure for internal financial and operational decision-making purposes and as a means to evaluate period-to-period comparisons of the performance and results of operations of our core business. Our management believes that these non-GAAP financial measures provide meaningful supplemental information regarding the performance of our business by excluding non-cash expenses that may not be indicative of our recurring operating results. We believe this non-GAAP financial measure is useful to investors as they allow for greater transparency with respect to key metrics used by management in its financial and operational decision making.

"EBITDA"- is defined as earnings (loss) before interest expense, income tax expense and depreciation and amortization expense.

"Adjusted EBITDA"- is defined as EBITDA adjusted to exclude (i) stock-based compensation and (ii) other non-cash expenses.