On March 3, 2022 TG Therapeutics, Inc. (NASDAQ: TGTX), reported the U.S. Food and Drug Administration (FDA) has extended the Prescription Drug User Fee Act (PDUFA) goal date to June 25, 2022 for the Biologics License Application (BLA) and supplemental New Drug Application (sNDA) for ublituximab in combination with UKONIQ (umbralisib) as a treatment for patients with chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) (Press release, TG Therapeutics, MAR 3, 2022, View Source [SID1234609444]).

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The FDA notified the Company that the updated overall survival analyses which were submitted to the FDA in February 2022, constituted a major amendment to the applications, and therefore the FDA is extending the PDUFA date to provide time for a full review of the submissions.

Michael S. Weiss, Chairman and Chief Executive Officer of TG Therapeutics stated, "As mentioned on our earnings call earlier this week, we believed an extension of the PDUFA date was a likely scenario especially given the proposed timing of the upcoming ODAC meeting. We hope this extension provides the time needed to give proper attention and review to the U2 BLA/sNDA." Mr. Weiss continued, "We continue to believe in the potential of U2 to provide a meaningful treatment option to patients with CLL and SLL."

ABOUT THE ODAC MEETING
In general, the Oncologic Drugs Advisory Committee (ODAC) reviews and evaluates data concerning the safety and effectiveness of marketed and investigational human drug products for use in the treatment of cancer and makes appropriate recommendations to the Commissioner of Food and Drugs. Although the FDA will consider the recommendation of the ODAC Committee, the final decision regarding the approval of a product is made solely by the FDA.

The FDA has notified the Company that potential questions and discussion topics for the ODAC include: the benefit-risk of the U2 combination in the treatment of CLL or SLL, and the benefit-risk of UKONIQ in relapsed/refractory marginal zone lymphoma (MZL) or follicular lymphoma (FL). In addition, as part of the benefit-risk analysis, the overall safety profile of the U2 regimen, including adverse events (serious and Grade 3-4), discontinuations due to adverse events, and dose modifications, is expected to be reviewed. The FDA’s concern giving rise to the ODAC meeting appears to stem from an early analysis of overall survival from the UNITY-CLL trial.

Overall survival was designated as a secondary efficacy outcome in the UNITY-CLL protocol but was not part of the primary analysis in accordance with the study’s statistical analysis plan agreed upon via a Special Protocol Assessment (SPA), and therefore, was not analyzed or included in the BLA/sNDA. Additionally, the study was not powered for overall survival. As part of the ongoing review of the BLA/sNDA, the FDA requested an early analysis of overall survival from the UNITY-CLL trial. As of September 2021, the cut-off date for the overall survival analysis requested by the FDA during their review, there was an imbalance in favor of the control arm (HR: 1.23) though this result was not statistically significant. However, when excluding deaths related to COVID-19, the two arms were approximately balanced (HR: 1.04) with again no statistically significant difference between the treatment groups with regard to overall survival. In February 2022, the Company submitted updated overall survival data with the same September 2021 cut-off date. The Company will continue to evaluate this endpoint over time as more events are available and will continue to analyze how COVID-19 may be impacting the analysis.

The date of the ODAC meeting has not yet been determined, although the FDA has stated that it is targeting holding the ODAC in March or April 2022.

ABOUT UNITY-CLL PHASE 3 TRIAL AND THE BLA/sNDA SUBMISSION
UNITY-CLL is a global, Phase 3, randomized, controlled clinical trial comparing the combination of ublituximab plus UKONIQ (umbralisib), or U2, to an active control arm of obinutuzumab plus chlorambucil in patients with both treatment-naïve and relapsed or refractory chronic lymphocytic leukemia (CLL). The trial randomized patients into four treatment arms: ublituximab single agent, UKONIQ single agent, ublituximab plus UKONIQ, and an active control arm of obinutuzumab plus chlorambucil. A prespecified interim analysis was conducted to assess the contribution of ublituximab and UKONIQ in the U2 combination arm and allowed for the termination of the single agent arms. Accordingly, the UNITY-CLL Phase 3 trial continued enrollment in a 1:1 ratio into the two combination arms: the investigational arm of U2 and the control arm of obinutuzumab plus chlorambucil. Approximately 420 subjects enrolled to the two combination arms and approximately 60% of patients were treatment-naïve and 40% were relapsed or refractory. The primary endpoint for this study was superior progression-free survival (PFS) for the U2 combination compared to the control arm. The trial met its primary endpoint, with U2 significantly prolonging independent review committee (IRC) assessed PFS vs. control (median 31.9 months vs 17.9 months; hazard ratio 0.546 (p<0.0001)) at a median follow-up of 36.7 months, and results were presented at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in December 2020. The UNITY-CLL Phase 3 trial is being conducted under a Special Protocol Assessment (SPA) agreement with the U.S. Food and Drug Administration (FDA).

The BLA/sNDA submissions of U2 to treat CLL were based on the results of the UNITY-CLL trial. The FDA previously granted Fast Track designation to the U2 combination for the treatment of adult patients with CLL and orphan drug designation for ublituximab in combination with UKONIQ for the treatment of CLL.

ABOUT CHRONIC LYMPHOCYTIC LEUKEMIA
Chronic lymphocytic leukemia (CLL) is the most common type of adult leukemia. It is estimated there will be more than 20,000 new cases of CLL diagnosed in the United States in 2020 and approximately 45,000 new cases globally in 2020.1,2 Although signs and symptoms of CLL may disappear for a period of time after initial treatment, the disease is considered incurable and many people will require additional treatment due to the return of malignant cells.

On March 3, 2022 Terns Pharmaceuticals, Inc. ("Terns" or the "Company") (Nasdaq: TERN), a clinical-stage biopharmaceutical company developing a portfolio of small-molecule single-agent and combination therapy candidates to address serious diseases, such as non-alcoholic steatohepatitis (NASH) and obesity, reported financial results for the fourth quarter and full year ended December 31, 2021 and corporate highlights (Press release, Terns Pharmaceuticals, MAR 3, 2022, View Source [SID1234609460]).

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"2021 was a cornerstone year for Terns, during which we demonstrated monotherapy proof of concept for TERN-501 and TERN-101, nominated an oral small-molecule GLP-1 receptor agonist, TERN-601, as our development candidate to explore various metabolic diseases such as obesity, augmented our leadership team with key hires, and strengthened our financial position though our IPO," said Senthil Sundaram, chief executive officer at Terns. "We look forward to continuing our momentum with top-line data from the AVIATION trial of TERN-201 in NASH patients later this month. With four differentiated single-agent drug candidates under development, and our first combination therapy trial in NASH expected to initiate in the first half of 2022, we are rapidly advancing and broadening our pipeline to address serious diseases such as NASH and obesity."

Recent Developments and Anticipated Milestones

TERN-201: Vascular adhesion protein-1 (VAP-1) inhibitor

Top-line data from AVIATION Trial Part 1 (10 mg) and Part 2 (20 mg) expected in March 2022 and the second half of 2022, respectively, including:
Safety and tolerability
Key imaging endpoint: Corrected T1 (cT1), an imaging marker of liver inflammation and fibrosis linked to clinical outcomes
Serum markers: CK-18, ALT, plasma VAP-1 activity
Initiated Part 2 of Phase 1b AVIATION Trial in the first quarter of 2022
Part 2 will evaluate 20 mg of TERN-201 vs placebo for 12 weeks
TERN-501: Thyroid hormone receptor-beta (THR-β) agonist

Announced positive top-line single-ascending and multiple-ascending dose (SAD/MAD) data from Phase 1 proof of concept clinical trial in November 2021, including a presentation of SAD data at AASLD’s The Liver Meeting Digital Experience 2021, demonstrating:
Significant, dose-dependent effects on sex hormone binding globulin (SHBG), a key pharmacodynamic marker of THR-β engagement linked to NASH histologic efficacy
TERN-501 was generally well-tolerated
Predictable pharmacokinetic profile with low variability and median half-life supportive of once-daily dosing
Potential to be a best-in-class THR-β agonist monotherapy and the THR-β agonist of choice for coformulations of fixed-dose combinations for the treatment of NASH
Data support planned initiation in 1H 2022 of Terns’ first Phase 2a trial of TERN-501 alone and in combination with farnesoid X receptor (FXR) agonist TERN-101 in NASH patients with top-line data expected in 2H 2023
TERN-101: Liver-distributed FXR agonist

Announced positive data from Phase 2a LIFT Trial in NASH in June 2021, including multiple presentations at AASLD in November 2021, demonstrating:
TERN-101 was generally well-tolerated at all doses studied with no discontinuations due to adverse events, including pruritus
cT1, an imaging marker of liver inflammation and fibrosis linked to clinical outcomes, declined significantly as early as Week 6 with persistent decreases through Week 12 in all TERN-101 groups compared to placebo, with cT1 changes at Week 6 strongly correlated with changes at Week 12
TERN-101 treatment led to study population shifts to cT1 categories associated with lower risk of clinical events in chronic liver disease patients
In 5 and 10 mg groups of TERN-101, no differences from placebo in percentage change of low-density lipoprotein cholesterol and high-density lipoprotein cholesterol from baseline to Week 12
Data support planned initiation in 1H 2022 of Terns’ first Phase 2a trial of TERN-101 alone and in combination with THR-β agonist TERN-501 in NASH patients with top-line data expected in 2H 2023
TERN-601: Glucagon-like peptide-1 (GLP1) receptor agonist

TERN-601 candidate nominated at year-end 2021 as an oral, small-molecule GLP-1 receptor agonist targeting metabolic diseases such as obesity and NASH with the potential for once-daily dosing
Synthetic GLP-1 peptides have been approved for indications such as diabetes and obesity, which are conditions often accompanying NASH
Terns plans to engage in IND-enabling activities for TERN-601 with the goal of initiating a first-in-human clinical trial in 2023
Key Appointments

Diana Chung was promoted to senior vice president, chief development officer in January 2022, and was previously senior vice president, clinical development and operations at Terns
Jeffrey Jasper, Ph.D. joined Terns in December 2021 as senior vice president, head of research, bringing more than 28 years of experience in the biopharmaceutical industry
Ann E. Taylor, M.D. joined the Board of Directors in September 2021, bringing more than 35 years of experience in drug development, having served most recently as chief medical officer of AstraZeneca plc
Pamela Danagher joined Terns as vice president and head of regulatory affairs in August 2021, bringing more than 20 years of experience in the pharmaceutical and biotechnology sectors
Terns was appointed to the Steering Committee of the NAIL-NIT Consortium, a multi-stakeholder effort to link non-invasive tests (NITs) directly to liver-related outcomes and accelerate the usage of NITs as surrogate endpoints for NASH
Fourth Quarter and Full Year Financial Results

Cash Position: As of December 31, 2021, cash, cash equivalents and marketable securities were $166.0 million as compared with $74.9 million as of December 31, 2020. Terns completed an upsized initial public offering in February 2021, raising $146.6 million in gross proceeds. Based on its current operating plan, Terns expects these funds will be sufficient to support its planned operating expenses into 2024, including through the clinical readout of its planned NASH Phase 2a combination trial of TERN-501 and TERN-101.
Research and Development (R&D) Expenses: R&D expenses were $9.5 million and $31.3 million for the quarter and year ended December 31, 2021, respectively, as compared with $7.8 million and $28.0 million for the quarter and year ended December 31, 2020, respectively.
General and Administrative (G&A) Expenses: G&A expenses were $5.4 million and $19.5 million for the quarter and year ended December 31, 2021, respectively, as compared with $1.0 million and $9.0 million for the quarter and year ended December 31, 2020, respectively.
Net Loss: Net loss was $14.2 million and $50.2 million for the quarter and year ended December 31, 2021, respectively, as compared with $9.9 million and $40.6 million for the quarter and year ended December 31, 2020, respectively.

On March 3, 2022 Helsinn Group (Helsinn), a fully integrated, global biopharma company with a diversified pipeline of innovative oncology assets and strong track-record of commercial execution, and BridgeBio Pharma, Inc. (Nasdaq: BBIO) (BridgeBio), a commercial-stage biopharmaceutical company that focuses on genetic diseases and cancers, reported an update to their existing strategic collaboration to develop, manufacture and commercialize infigratinib for oncology indications (Press release, BridgeBio, MAR 3, 2022, View Source [SID1234609476]).

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Under the terms of the amended and restated agreement, Helsinn will gain an exclusive license to commercialize infigratinib in the U.S. and will be responsible for developing, manufacturing and commercializing infigratinib in oncology indications worldwide except for achondroplasia or any other skeletal dysplasias and except in mainland China, Hong Kong and Macau. BridgeBio will be eligible to receive regulatory and commercial milestone payments as well as tiered royalties on adjusted net sales from Helsinn. BridgeBio will retain all rights to develop, manufacture and commercialize infigratinib in skeletal dysplasia, including achondroplasia.

In 2021, Helsinn and BridgeBio obtained accelerated approval for TRUSELTIQ (infigratinib) from the U.S. Food and Drug Administration (FDA) for the treatment of adults with previously treated, unresectable locally advanced or metastatic cholangiocarcinoma with a fibroblast growth factor receptor 2 (FGFR2) fusion or other rearrangement as detected by an FDA-approved test. Additionally, the two parties received conditional approval by Health Canada and provisional approval by the Therapeutics Goods Association in Australia for TRUSELTIQ (infigratinib) for the treatment of adults with previously treated, unresectable locally advanced or metastatic cholangiocarcinoma with a FGFR2 fusion or other rearrangement. Continued approval in the U.S., Canada and Australia for this indication may be contingent upon confirmatory trials.

Infigratinib is not FDA-, Health Canada- or Therapeutics Goods Association-approved for any other indication in the United States, Canada and Australia, and is not approved for use by any other health authority.

Giorgio Calderari, Helsinn Group CEO commented, "We are delighted to gain the exclusive license to commercialize infigratinib in the U.S. This perfectly complements our recently announced Fully Integrated Targeted Therapy (FITT) Strategy and will utilize our unique capabilities and expertise to take products through development and to patients living with cancer across the globe. BridgeBio is a great partner, and we are looking forward to continuing our relationship with them through our non-exclusive collaboration framework to propose co-development and co-commercialization opportunities for preclinical precision oncology programs."

"We are expanding our partnership with Helsinn so that even more patients with FGFR-driven cancers will ultimately be able to access infigratinib. Focused execution means reducing the scope of our internal activity. We will continue to advance high-quality programs in our pipeline, while allowing Helsinn to develop and commercialize infigratinib in cancer indications for patients in need," said Neil Kumar, Ph.D., founder and CEO of BridgeBio.

In March 2021, Helsinn and BridgeBio entered into a global license and collaboration agreement to co-commercialize infigratinib for oncology in the U.S. and to co-develop, manufacture and commercialize infigratinib for such indications outside the U.S., excluding mainland China, Hong Kong and Macau. BridgeBio previously entered a strategic collaboration with LianBio for development and commercialization of infigratinib in oncology indications in mainland China, Hong Kong and Macau.

In November 2021, Helsinn and BridgeBio entered into a strategic collaboration to co-develop and co-commercialize a potentially first-in-class inhibitor designed to target glutathione peroxidase 4 (GPX4), which will be investigated in patients with difficult-to-treat tumors. Alongside this, Helsinn and BridgeBio established a new non-exclusive collaboration framework agreement that allows the companies to propose co-development and co-commercialization opportunities for preclinical precision oncology programs. The terms in this strategic collaboration have not changed.

About Infigratinib

Infigratinib is a potent orally administered, selective, ATP‐competitive, kinase inhibitor of FGFRs, with highest affinity for FGFR 1, 2, and 3. The therapy is currently under investigation as a potential first-line treatment for individuals with FGFR2-altered cholangiocarcinoma (bile duct cancer) and in the adjuvant setting for individuals with FGFR3-altered urothelial carcinoma (bladder cancer). Infigratinib is also in development in skeletal dysplasias for the treatment of individuals with FGFR3-altered achondroplasia. BridgeBio retains full rights to develop and commercialize infigratinib in skeletal dysplasias for the treatment of individuals with FGFR3-altered achondroplasia.

About Cholangiocarcinoma (CCA)

CCA represents an aggressive group of malignancies that form in the bile ducts. Although rare in most countries (with a worldwide estimated incidence of <6 per 100,000 people), the incidence of this malignancy is increasing worldwide. Because the disease is usually asymptomatic at early-stages, diagnosis may be delayed until advanced stages, when CCA typically presents as locally advanced or metastatic disease. Despite continuing advances in treatments, the prognosis for this disease remains poor, with a 5-year survival rate of <20%. FGFR2 genetic alterations are present in approximately 15% to 20% of CCA patients and represent potential targets for treatments.1,2

U.S. Indication and Important Safety Information for TRUSELTIQ (infigratinib)

TRUSELTIQ (infigratinib) capsules 25mg/100mg is indicated for the treatment of adults with previously treated, unresectable, locally advanced or metastatic cholangiocarcinoma with a fibroblast growth factor receptor 2 (FGFR2) fusion or other rearrangement as detected by an FDA-approved test.

Accelerated approval was granted based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification of clinical benefit in confirmatory trial(s).

Warnings and precautions

Ocular toxicity: Retinal pigment epithelial detachment (RPED), which may cause blurred vision, occurred in 11% of 351 patients treated with TRUSELTIQ, including patients with asymptomatic RPED, with a median onset of 26 days. Perform comprehensive ophthalmological exam including optical coherence tomography prior to initiating, at 1 month, at 3 months, and then every 3 months during treatment with TRUSELTIQ. Urgently evaluate patients for onset of visual symptoms and follow up every 3 weeks until resolved or TRUSELTIQ is discontinued. Withhold TRUSELTIQ as recommended. Dry eye occurred in 29% of 351 patients; treat with ocular demulcents as needed
Hyperphosphatemia and soft tissue mineralization: Hyperphosphatemia, which can lead to soft tissue mineralization, cutaneous calcinosis, non-uremic calciphylaxis, vascular calcification, and myocardial calcification, occurred in 82% of 351 patients treated with TRUSELTIQ, with a median time to onset of 8 days (range 1-349); 83% of 351 patients treated with TRUSELTIQ received phosphate binders. Monitor for hyperphosphatemia throughout treatment. Initiate phosphate-lowering therapy for serum phosphate >5.5 mg/dL; withhold TRUSELTIQ and initiate phosphate-lowering therapy for serum phosphate >7.5 mg/dL; withhold, reduce the dose, or permanently discontinue TRUSELTIQ based on duration and severity of hyperphosphatemia
Embryo-fetal toxicity: TRUSELTIQ can cause fetal harm. Advise pregnant women of the potential risk to the fetus; advise females of reproductive potential and men who are partnered with women of reproductive potential to use effective contraception during treatment with TRUSELTIQ and for 1 month after the final dose
Adverse reactions

Most common adverse reactions (incidence ≥20%, all grades): nail toxicity, stomatitis, dry eye, fatigue, alopecia, palmar-plantar erythrodysesthesia syndrome, arthralgia, dysgeusia, constipation, abdominal pain, dry mouth, eyelash changes, diarrhea, dry skin, decreased appetite, blurred vision, and vomiting
Most common laboratory abnormalities (incidence ≥20%, all grades): increased creatinine, increased phosphate, decreased phosphate, increased alkaline phosphatase, decreased hemoglobin, increased alanine aminotransferase, increased lipase, increased calcium, decreased lymphocytes, decreased sodium, increased triglycerides, increased aspartate aminotransferase (AST), increased urate, decreased platelets, decreased leukocytes, decreased albumin, increased bilirubin, and decreased potassium
Drug interactions

CYP3A inhibitors: Avoid use with strong and moderate CYP3A inhibitors
CYP3A inducers: Avoid use with strong and moderate CYP3A inducers
Gastric acid–reducing agents: Avoid coadministration with proton pump inhibitors, histamine-2 receptor antagonists (H2RA), and locally acting antacids. If coadministration of H2RA or locally acting antacids cannot be avoided, separate TRUSELTIQ administration
H2RA: Take TRUSELTIQ 2 hours before or 10 hours after
Locally-acting antacid: Take TRUSELTIQ 2 hours before or 2 hours after
Dosage and administration

Prior to initiating TRUSELTIQ: Confirm FGFR2 fusion or rearrangement; perform comprehensive ophthalmic exam including OCT; confirm negative pregnancy test in females of reproductive potential
Starting dose: Take TRUSELTIQ orally once daily on Days 1-21 of 28-day cycles; continue treatment until disease progression or unacceptable toxicity. Take TRUSELTIQ on an empty stomach with a glass of water at least 1 hour before or 2 hours after food
No renal or hepatic impairment
125 mg (one 100 mg capsule and one 25 mg capsule)
Mild and moderate renal impairment (creatinine clearance 30-89 mL/min)
100 mg (one 100 mg capsule)
Mild hepatic impairment (total bilirubin >upper limit of normal [ULN] to 1.5 x ULN or AST > ULN)
100 mg (one 100 mg capsule)
Moderate hepatic impairment (total bilirubin >1.5 to 3 x ULN with any AST)
75 mg (three 25 mg capsules)
Dose modification: Consult the TRUSELTIQ full Prescribing Information for dose modifications and monitoring recommendations for RPED, hyperphosphatemia, and other Grades 3-4 adverse reactions
For additional information, please see the U.S. Full Prescribing Information for TRUSELTIQ

References
1Banales, J., Cardinale, V., Carpino, G. et al. Cholangiocarcinoma: current knowledge and future perspectives consensus statement from the European Network for the Study of Cholangiocarcinoma (ENS-CCA). Nat Rev Gastroenterol Hepatol 13, 261–280 (2016). View Source

2 Banales, J.M., Marin, J.J.G., Lamarca, A. et al. Cholangiocarcinoma 2020: the next horizon in mechanisms and management. Nat Rev Gastroenterol Hepatol 17, 557–588 (2020). View Source

On March 3, 2022 Median Technologies (ALMDT) reported that the company has filed a 513(g) submission on Feb. 17, 2022 to the United States Food and Drug Administration (FDA) for its iBiopsy Lung Cancer Screening (LCS) AI/ML technology-based end-to-end CADe/CADx1 Software as Medical Device (SaMD) (Press release, MEDIAN Technologies, MAR 3, 2022, View Source [SID1234609491]).

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The 513(g) submission will allow Median Technologies to determine the best product classification and choose between the De Novo or the 510(k) regulatory pathways for iBiopsy LCS CADe/CADx SaMD. The FDA is expected to review the 513(g) submission and provide feedback within 60 calendar days.

As next regulatory steps, Median Technologies is preparing several Q-submissions for Q2, 2022.

"This first regulatory submission marks the beginning of our interactions with the FDA. The FDA’s feedback will help us determine the shortest and most efficient way to bring our product onto the US healthcare market", Fredrik Brag, CEO and founder of Median Technologies said. "Lung cancer is the deadliest cancer, and being able to detect it very early is of critical importance for patients. Our innovative iBiopsy AI/ML-based technology could have a huge impact on saving patients’ lives by identifying lung cancer onsets at their earliest stage, and could significantly improve the accuracy, consistency, and adoption of lung cancer screening programs worldwide".

About iBiopsy: iBiopsy is based on the most advanced technologies in Artificial Intelligence (AI) and Data Science (DS), benefiting from Median’s expertise in medical image processing. iBiopsy targets the development of innovative AI/ML-based Software as Medical Device, to be used in several indications for which there are unmet needs regarding early diagnosis, prognosis and treatment selection in the context of precision medicine. iBiopsy currently focuses on lung cancer, liver cancer (HCC) and liver fibrosis (NASH).

On March 3, 2022 CNS Pharmaceuticals, Inc. (NASDAQ: CNSP) ("CNS" or the "Company"), a biopharmaceutical company specializing in the development of novel treatments for primary and metastatic cancers in the brain and central nervous system, reported its financial results for the year ended December 31, 2021 and provided a clinical update of its anti-cancer drug candidates currently in development for the treatment of primary and metastatic brain and CNS cancer (Press release, CNS Pharmaceuticals, MAR 3, 2022, View Source [SID1234609445]).

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2021 Key Highlights

May 2021: Commenced patient enrollment in the potentially pivotal study (CNS-201) evaluating efficacy of Berubicin in the treatment of adult recurrent Glioblastoma Multiforme (rGBM), one of the most aggressive types of brain cancer;
June 2021: FDA granted Fast Track Designation to CNS Pharmaceuticals for Berubicin for the treatment of recurrent GBM;
September 2021: Dosed first group of patients with Berubicin in the potentially pivotal study for the treatment of GBM;
December 2021: Received approval from "swissethics," the umbrella organization of the cantonal Ethics Committees (EC) in Switzerland, for the Company’s potentially pivotal study of Berubicin for the treatment of recurrent GBM; and
January 6, 2022: Announced a $11.5M private placement, priced at-the-market under Nasdaq rules.
"Operationally 2021 was a terrific year for the Company as we established the global framework for building and expanding our potentially pivotal clinical study of berubicin for the treatment of GBM. Our priority remains focused on advancing berubicin to bring a meaningful treatment to patients, families and clinicians, who currently have extremely limited and often ineffective treatment options. I am continually impressed by the speed and efficiency with which our small team has executed our Berubicin trial. At the onset of 2022 we completed a $11.5 million private placement which enables us to continue driving the development of berubicin this year towards the milestones ahead of us," commented John Climaco, CEO of CNS Pharmaceuticals. "While staying steadfast in our primary goal of bringing berubicin to GBM patients, we are also continually evaluating platform opportunities for expansion into additional oncology indications to bolster our pursuit of therapies for patients through developing novel treatments for primary and metastatic cancers. I am very pleased with the progress we’ve made over the past year, but am even more so looking forward to what lays ahead for CNS Pharmaceuticals."

Clinical Programs Update

Berubicin – Novel anthracycline

CNS’ lead product candidate, Berubicin, is a novel anthracycline and the first anthracycline to appear to cross the blood-brain barrier. Berubicin is currently in development for the treatment of a number of serious brain and CNS oncology indications. In mid-2021 the Company announced it has dosed the first group of patients in its potentially pivotal study evaluating the efficacy of Berubicin in the treatment of adult GBM, one of the most aggressive types of brain cancer. Further patient enrollment, randomization and dosing is currently underway as well as a robust lineup of clinical sites located globally which are advancing toward activation and enrollment.

The FDA granted CNS Pharmaceuticals Fast Track Designation for Berubicin which enables more frequent interactions with the FDA to expedite the development and review process. As previously announced, the Company also received Orphan Drug Designation from the FDA which may provide seven years of marketing exclusivity upon approval of an NDA.

For more information about the potentially pivotal Berubicin trial, visit clinicaltrials.gov and reference identifier NCT04762069.

Upcoming Milestones

Expand potentially pivotal study to evaluate efficacy of Berubicin in the treatment of adult GBM into additional countries;
Interim analysis of the trial when 30-50% of the total expected patients have been on study for 6 months (expected during first half of 2023); and
Complete enrollment in potentially pivotal clinical trial for GBM.
WP1244 Portfolio – Novel class of DNA-binding agents

The Company continues to advance the development of its WP1244 drug technology, which utilizes anthracycline and distamycin-based scaffolds to create small molecule agents and is believed to be 500x more potent than daunorubicin in inhibiting tumor cell proliferation. Preclinical studies of WP1244 demonstrated high uptake in the brain with antitumor activity. The Company’s development work has produced a new mesylate salt of WP1244, now identified as WP1874. The enhanced solubility of this salt may increase its ability to be formulated for use in an IV infusion, while maintaining similar potency and toxicity characteristics. Going forward, WP1874 will be the primary focus in our development efforts of the WP1244 portfolio. CNS Pharmaceuticals is also evaluating the use of WP1244/WP1874 in the treatment of other primary brain and central nervous system cancers, as well as cancers metastatic to the brain including pancreatic, ovarian, and lymphomas.

Upcoming Milestones

File IND in 2023.
Summary of Financial Results for the Full Year 2021

The net loss for the year ended December 31, 2021 was approximately $14.0 million compared to approximately $9.5 million for the comparable period in 2020. The change in net loss is attributable to increased personnel and activity associated with preparing for and commencing the Company’s potentially pivotal clinical trial of Berubicin for recurrent glioblastoma multiforme in 2021. The Company reported research and development expenses of $9.3 million for the year ended December 31, 2021 compared to approximately $5.1 million for the comparable period in 2020. The expenses incurred during the period were related to drug manufacturing and labor related to the preparation for and commencement of the Company’s potentially pivotal Berubicin study. General and administrative expense was approximately $4.7 million for the year ended December 31, 2021 compared to approximately $4.4 million for the comparable period in 2020.

As of December 31, 2021, the Company had cash of approximately $5.0 million and working capital of approximately $5.3 million. In early January 2022, the Company completed an offering of common stock and warrants for gross proceeds of $11.5 million. Our current expectation is that our cash on hand and the proceeds from the offering during January is sufficient to fund our operations into the first quarter of 2023. The timing and costs of clinical trials are difficult to predict and trial plans may change in response to evolving circumstances and as such the foregoing estimates may prove to be inaccurate.