On March 31, 2022 Canthera Discovery reported that its predecessor, Cancer Therapeutics CRC, received the Cooperative Research Australia (CRA) Excellence in Innovation Award for Research Commercialisation at an award ceremony at Parliament House in Canberra on Thursday night (Press release, Canthera Discovery, MAR 31, 2022, View Source [SID1234611332]).

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Cancer Therapeutics CRC, ran for 13 years (2007-2020) and was recognised for landing deals in ground-breaking cancer therapies with pharma giants for a headline value of close to A$1.4bn. It has 7 licensed programs in active development, including two currently in clinical trials.

"The CRC Program funded Cancer Therapeutics CRC with $71m over 13 years. In potentially returning some ten times that investment and counting in licensing deals, Cancer Therapeutics CRC and Canthera Discovery have been a shining example of the strength of the CRC Program in bridging the gap between domestic world class research and innovation, and global commercialisation," CRA CEO Jane O’Dwyer said.

"Cooperative Research Australia is delighted to present Canthera Discovery and Cancer Therapeutics CRC with the Award for Research Commercialisation," she said.

Brendon Monahan, Chief Scientific Officer, Canthera Discovery
Upon receiving the award, Brendon Monahan, Canthera Discovery Chief Scientific Officer commented, "Drug discovery requires a multi-disciplinary approach and collaboration is at the centre of everything we do. We would like to thank and acknowledge our Research Partners: WEHI, CSIRO, Monash University, Griffith University, Children’s Cancer Institute, and the Peter MacCallum Cancer Centre. Our CRC commercialisation partners SYNthesis Research and Oncology One. And all of our CRC participants."

"It is no secret that what has driven the success of Cancer Therapeutics CRC and now Canthera, is its people. The KAT6 project alone, which entered clinical trials in 2020, involved over 100 people, across 16 organisations, 10 research laboratories, and 11 different general fields combining science, business, and data management. We thank everyone, past and present, who have contributed expertise, creativity, and passion to our organisation and projects."

On March 31, 2022, United Therapeutics Corporation (the "Company") reported that entered into a Credit Agreement (the "Credit Agreement") with certain of its subsidiaries party thereto, as guarantors (the "Guarantors"), the lenders referred to therein, and Wells Fargo Bank, National Association ("Wells Fargo"), as administrative agent and as a swingline lender (Filing, 8-K, United Therapeutics, MAR 31, 2022, View Source [SID1234611348]). The Credit Agreement provides for (i) an unsecured, revolving credit facility of up to $1.2 billion; and (ii) a second unsecured, revolving credit facility of up to $800 million (which facilities may, subject to obtaining commitments from existing or new lenders for such increase and subject to other condition, be increased by up to $500 million in the aggregate). The facilities mature five years after the closing date of the Credit Agreement, subject to an ability of the lenders thereunder, or certain of the lenders thereunder, to elect to extend the maturity date of their commitments by one year following a request for such extension by the Company in accordance with the terms of the Credit Agreement, up to a maximum of two such extensions.

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As of March 31, 2022, Lung Biotechnology PBC is the only subsidiary of the Company required to be a Guarantor and guarantee the Company’s obligations under the Credit Agreement. From time to time, one or more additional subsidiaries of the Company may be required to guarantee the Company’s obligations under the Credit Agreement.

At the Company’s option, the loan will bear interest at either an adjusted Term SOFR rate or a fluctuating base rate, in each case, plus an applicable margin that is determined on a quarterly basis based on the Company’s consolidated total leverage ratio (as calculated in accordance with the Credit Agreement).

The proceeds of borrowings under the Credit Agreement are available to refinance certain existing indebtedness of the Company and its subsidiaries and/or for working capital and other general corporate purposes. Upon closing of the Credit Agreement on March 31, 2022, the Company borrowed $800.0 million under the Credit Agreement, and used the funds to repay outstanding indebtedness under the 2018 Credit Agreement discussed under Item 1.02 below.

The Credit Agreement also contains customary affirmative and negative covenants that, among other things, limit the ability of the Company and its subsidiaries to: (a) incur indebtedness; (b) grant liens; (c) enter into a merger, consolidation, or amalgamation; (d) liquidate, wind up, or dissolve; or (e) sell all or substantially all of the property, business, or assets of the Company and its subsidiaries taken as a whole. In addition, as of the last day of each fiscal quarter, the Company must not permit (i) a consolidated ratio of total indebtedness to EBITDA to be greater than 3.00 to 1.00 (which ratio may, upon consummation of certain qualifying acquisitions, be increased to 3.50 to 1.00 for four fiscal quarters following such acquisition); and (ii) its consolidated interest coverage ratio to be less than 3.00 to 1.00, in each case calculated in accordance with the Credit Agreement.

The Credit Agreement contains customary events of default, including a change of control. Upon the occurrence and continuation of an event of default, all amounts due under the Credit Agreement and the other loan documents become (in the case of a bankruptcy event), or may become (in the case of all other events of default and at the option of the lenders), immediately due and payable.

On March 31, 2022 Genprex, Inc. ("Genprex" or the "Company") (NASDAQ: GNPX), a clinical-stage gene therapy company focused on developing life-changing therapies for patients with cancer and diabetes, reported the opening for patient enrollment of its Acclaim-2 clinical trial. Acclaim-2 is an open-label, multi-center Phase 1/2 clinical trial evaluating the Company’s lead drug candidate, REQORSA Immunogene Therapy, in combination with Keytruda (pembrolizumab) in patients with late-stage non-small cell lung cancer (NSCLC) whose disease progressed after treatment with Keytruda (Press release, Genprex, MAR 31, 2022, View Source [SID1234611241]). In 2021, Genprex received U.S. Food and Drug Administration’s (FDA) Fast Track Designation for treatment of the Acclaim-1 patient population.

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"We are pleased to have opened Acclaim-2 for patient enrollment and expect to promptly begin screening patients for their eligibility to participate in the trial," stated Mark S. Berger, M.D., Chief Medical Officer of Genprex. "This marks an important milestone in our clinical development program for REQORSA as we continue to engage with prestigious clinical trial sites to build patient enrollment and provide hope to lung cancer patients who suffer from this devastating disease and who are in desperate need of new treatment options. We look forward to completing the Phase 1 portion of Acclaim-2 by the end of the first quarter of 2023 and to generating data to show the synergistic effects REQORSA combined with immunotherapies can have in patients."

Previously presented preclinical data have shown synergy between REQORSA and Keytruda. Those data showed that REQORSA combined with the checkpoint inhibitor Keytruda was more effective than Keytruda alone in increasing the survival of mice with a humanized immune system that had metastatic lung cancer. Those studies in mice with a humanized immune system also documented multiple effects of REQORSA on the immune system, such as an increase in Natural Killer cells and a decrease in myeloid derived suppressor cells in the tumor, that are likely to contribute to the synergy seen with Keytruda.

The Company expects the Phase 1 portion of the Acclaim-2 trial to enroll up to 30 patients in a dose escalation study to determine the maximum tolerated dose of the combination of REQORSA and Keytruda. The Phase 2 portion of the study is expected to enroll approximately 126 patients to be randomized 2:1 to receive either REQORSA and Keytruda combination therapy or docetaxel and/or ramucirumab. The primary endpoint of the Phase 2 portion of the trial is progression-free survival, which is defined as time from randomization to progression or death. An interim analysis will be performed after 50 events. Genprex expects to complete the Phase 1 portion of Acclaim-2 by the end of the first quarter of 2023.

In 2020, Genprex entered into a worldwide, exclusive license agreement with a major cancer research center in Houston, Texas for the use of REQORSA in combination with immunotherapies, including Keytruda, and also for the use of REQORSA in a three-drug combination of TUSC2, immunotherapy and chemotherapy.

Keytruda is a registered trademark of Merck & Co. and is its largest selling drug with 2021 sales of more than $17 billion.

About REQORSA

REQORSA Immunogene Therapy (quaratusugene ozeplasmid) for non-small cell lung cancer (NSCLC) uses Genprex’s unique, proprietary ONCOPREX Nanoparticle Delivery System, which is the first systemic gene therapy delivery platform used for cancer in human clinical trials.

The active ingredient in REQORSA is the TUSC2 gene, a tumor suppressor gene. REQORSA consists of the TUSC2 gene encapsulated in a nanoparticle made from lipid molecules with a net positive electrical charge. REQORSA is injected intravenously and can specifically target cancer cells, which generally have a negative electrical charge. Once REQORSA is taken up into a cancer cell, the TUSC2 gene is expressed, and the TUSC2 protein is capable of restoring certain defective functions arising in the cancer cell. REQORSA has a multimodal mechanism of action whereby it interrupts cell signaling pathways that cause replication and proliferation of cancer cells, re-establishes pathways for programmed cell death, or apoptosis, in cancer cells, and modulates the immune response against cancer cells. REQORSA has also been shown to block mechanisms that create drug resistance.

On March 31, 2022 Allist Pharmaceuticals Co., Ltd., reported that the European Lung Cancer Congress (ELCC) published an abstract detailing results from the FURLONG study, a Phase 3 pivotal trial of Ivesa (Furmonertinib) in a first-line setting of patients with epidermal growth factor receptor (EGFR)-mutated, locally advanced or metastatic non-small cell lung cancer (NSCLC) (Press release, ArriVent Biopharma, MAR 31, 2022, https://arrivent.com/ivesa-demonstrates-progression-free-survival-of-over-20-months-in-first-line-setting-for-egfr-mutated-advanced-nsclc/ [SID1234611280]). The FURLONG study demonstrated that first-line treatment with Ivesa resulted in a median progression-free survival (PFS) of 20.8 months and reduced the risk of disease progression or death by 56% compared to Gefitinib.

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The FURLONG study was sponsored by Shanghai Allist Pharmaceuticals Co., Ltd. (hereinafter referred to as "Allist", Stock Code: 688578), and led by Professor Yuankai Shi from Cancer Hospital Chinese Academy of Medical Sciences.

Key Results

FURLONG is a national multi-center, randomized, double-blind, placebo-controlled, Phase 3 study designed to assess the efficacy and safety of Ivesa (Furmonertinib) versus Iressa (Gefitinib) in treatment-naïve patients with locally advanced or metastatic EGFRm NSCLC.

The final results show that the median PFS is significantly prolonged with Ivesa compared to Gefitinib group by 9.7 months (PFS, 20.8 months vs 11.1 months, hazard ratio [HR] 0.44 [95% confidence interval 0.34-0.58], p<0.0001), and the risk of disease progression or death was reduced by 56%. Despite the longer exposure, the incidence of grade ≥ 3 adverse reactions of Ivesa group is still lower than that of the Gefitinib group (11% vs 18%).

The release of breakthrough results of FURLONG study further concluded that first-line Ivesa provided a significant improvement versus the comparator first-generation EGFR-TKI in patients with EGFR-mutated advanced NSCLC. Ivesa is the only third-generation EGFR TKI that showed the primary endpoint PFS value beyond 20 months and the risk of disease progression or death reduced by 56% in a pivotal stage study versus a first-generation EGFR-TKI.

The detail of FURLONG study results will be released in the form of Proffered Paper session at ELCC on March 31, 2022.

Comments from Professor Yuankai Shi, Principal Investigator of FURLONG study, from National Cancer Center/Cancer Hospital Chinese Academy of Medical Sciences:

"Lung cancer is one of the malignant tumors with highest incidence rate and mortality rate in China. The EGFR mutation is the most common driven gene mutation in lung cancer. There is still an unmet clinical demand for the first-line treatment of NSCLC patients harboring EGFR sensitive mutations. The results of the FURLONG study are so exciting that Furmonertinib showed median PFS of 20.8 months as the first line treatment with favorable safety profile, providing an additional and better option for the first-line treatment for patients with locally advanced or metastatic NSCLC harboring EGFR sensitive mutations."

On March 31 2022 Inhibikase Therapeutics, Inc. (Nasdaq: IKT) (Inhibikase or Company), a clinical-stage pharmaceutical company developing therapeutics to modify the course of Parkinson’s disease and related disorders, reported financial results for the full year ended December 31, 2021 and highlighted recent developments (Press release, Inhibikase Therapeutics, MAR 31, 2022, View Source [SID1234611296]).

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"2021 was an important year for Inhibikase as we advanced our lead program IkT-148009 for Parkinson’s disease into the clinic, continued to develop our early-stage pipeline programs and strengthened our balance sheet to support our development efforts well into 2023," commented Dr. Milton H. Werner, President and Chief Executive Officer of Inhibikase. "Just recently, we presented results from our Phase 1 and 1b study of IkT-148009 in patients with mild to moderately advanced Parkinson’s disease at the annual AD/PD meeting. We believe these data continue to validate the safety and therapeutic potential of IkT-148009. As we look ahead, we hope to share more about our development strategy for this program including the upcoming Phase 2a study at our upcoming virtual KOL investor event on April 20th. Looking to our earlier programs, we are also continuing to advance IkT-148009 in animal models of Multiple Systems Atrophy (MSA), as well as plan to submit our IND application for IkT-001Pro, both in the second quarter. We view 2022 as a year of execution across our pipeline and look forward to providing updates throughout the year as we seek to improve the lives of patients suffering from a devastating neurodegenerative disease."

Recent Developments and Upcoming Milestones:

Phase 1b clinical trial of IkT-148009: The Phase 1b study is a 3:1 randomized, placebo-controlled dose escalation trial evaluating the safety, tolerability, and pharmacokinetics of seven-day dosing of IkT-148009 at three escalating dose levels. The study is also assessing motor and non-motor function, gut motility, and measures of alpha-synuclein aggregate clearance as exploratory endpoints. In March, the Company presented data from the first cohort at the Alzheimer’s & Parkinson’s Diseases Conference (AD/PD). Data demonstrated that the safety and tolerability profile in patients closely matched that of older healthy volunteers. Pharmacokinetics of IkT-148009 in volunteers and subjects was also similar, indicating that IkT-148009 pharmacology is consistent across the patient groups and penetrates the Central Nervous System. The Company expects to complete dosing of the Phase 1b study in the second quarter of 2022 and present full data at a medical meeting later this year.

Phase 1 dose escalation of IkT-148009 in older and elderly healthy volunteers: Inhibikase continues to evaluate IkT-148009 in older and elderly healthy volunteers as part of the Phase 1 study. The Company has completed dose escalation studies through 325 mg. To date, no clinically significant adverse events have been observed at any dose.

Phase 2a clinical study for IkT-148009 in patients with Parkinson’s Disease: Inhibikase expects to dose the first patient in a Phase 2a study of IkT-148009 in untreated Parkinson’s Disease in the second quarter of 2022, subject to agreements with the FDA. The 3:1 randomized, double-blind, twelve-week dosing trial will evaluate the safety and tolerability of three doses of IkT-148009 in up to 120 patients diagnosed with Parkinson’s disease who have not yet progressed to the need for symptomatic therapy. The trial will also measure motor and non-motor function inside and outside of the brain as secondary endpoints and evaluate whether treatment with IkT-148009 leads to a reduction or clearance of pathogenic alpha-synuclein aggregates as exploratory endpoints.

Investigational New Drug application (IND) for IkT-001Pro for stable-phase Chronic Myelogenous Leukemia (CML): IkT-001Pro is the Company’s prodrug formulation of Imatinib mesylate, designed as a potentially safer, better tolerated treatment for Imatinib-sensitive cancers such as stable-phase Chronic Myeloid Leukemia (CML). The Company is completing clinical batch manufacturing of pill formulated IkT-001Pro and conducting required stability studies and expects to submit the IND for IkT-001Pro in the second quarter of 2022. The Company expects to commence bioequivalence studies in accordance with the 505(b)(2) regulatory pathway agreements with the FDA.

Preclinical studies evaluating IkT-148009 in animal models of Multiple System Atrophy (MSA) in preparation for Phase 2 clinical studies: Inhibikase expects to report preclinical data studying IkT-148009 in at least one of two animal models of MSA prior to dosing of MSA patients. The studies are evaluating whether inhibition of the Abelson Tyrosine Kinase, or c-Abl, could have a therapeutic benefit in MSA. The potential role of c-Abl in the disease process was highlighted in the Company’s recent publication published in the peer reviewed journal Neurobiology of Disease[1]. Depending on the preclinical results in animal models of MSA and subject to agreement with the FDA and equivalent regulatory bodies in the European Union, Inhibikase may advance IkT-148009 into a Phase 2a clinical study in the third quarter of 2022.
Upcoming Events:

Virtual KOL Investor Event
Date: April 20, 2022
Time: 10:00am ET
Registration Link: View Source

Inhibikase’s executive leadership team and featured Key Opinion Leaders will host a virtual presentation highlighting the Company’s recent clinical progress including a review of the recently reported Phase 1 data for its lead asset, IkT-148009 as well as an overview of the upcoming Phase 2 program. Additional presentations will highlight the current unmet need and competitive landscape in Parkinson’s disease.

Full Year 2021 Financial Results

Grant Revenue: Grant revenue was $3.1 million for the year ended December 31, 2021 compared to $0.7 million in the prior year. The increase was driven by increased grant research activity during 2021 compared to 2020. During 2020, the Company’s focus was shifted toward advancing its Phase I clinical trials which did not result in grant revenue. The Company utilized its working capital and personnel resources in 2021 to carry on its Phase I clinical trial in addition to its grant research activity.

R&D Expenses: Research and development expenses were $11.4 million for the year ended December 31, 2021 compared to $0.9 million in the year ended December 31, 2020. The increase was primarily due to a full year of increased activity in our Parkinson’s disease Phase I clinical trial.

SG&A Expenses: Selling, general and administrative expenses for the year ended December 31, 2021 were $6.5 million compared to $2.6 million for the year ended December 31, 2020. The increase was primarily due to increased liability insurance, legal and accounting fees, board costs, investor relations and consulting fees associated with operating for the first full year as a public company.

Net Loss: Net loss for the year ended December 31, 2021 was $14.8 million, or $0.81 per share, compared to a net loss of $2.8 million, or $0.35 per share in the year ended December 31, 2020.

Cash Position: Cash and cash equivalents were $40.8 million as of December 31, 2021. The Company expects that existing cash and cash equivalents will be sufficient to fund its operating expenses and capital expenditure requirements into the third quarter of 2023.