GILEAD SCIENCES ANNOUNCES COMPLETION OF ACQUISITION OF CYMABAY

On March 22, 2024 Gilead Sciences, Inc. (Nasdaq: GILD) reported the completion of the previously announced transaction to acquire CymaBay Therapeutics, Inc. (Nasdaq: CBAY) for approximately $4.3 billion in total equity value (Filing, 8-K, Gilead Sciences, MAR 22, 2024, View Source [SID1234641381]). The addition of CymaBay’s investigational lead product candidate, seladelpar for the treatment of primary biliary cholangitis (PBC) including pruritus, complements Gilead’s existing liver portfolio and aligns with its long-standing commitment to bringing transformational medicines to patients.

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"The acquisition of CymaBay brings us a potential best in disease therapy that could transform the treatment landscape for people with primary biliary cholangitis," said Daniel O’Day, Chairman and Chief Executive Officer, Gilead Sciences. "I want to thank the CymaBay team for their efforts and commitment to addressing this high unmet need. We look forward to advancing seladelpar and building on Gilead’s more than 20-year legacy of treating and curing liver disease on a global scale."

On February 12, 2024, Gilead and CymaBay announced that CymaBay, Gilead and Pacific Merger Sub, Inc., a wholly owned subsidiary of Gilead ("Purchaser"), had signed a definitive merger agreement pursuant to which a tender offer would be made. Pursuant to the merger agreement, Gilead and Purchaser commenced a tender offer on February 23, 2024, to acquire all outstanding shares of CymaBay at a price of $32.50 per share. On March 22, 2024, Gilead successfully completed the tender offer for all outstanding shares of common stock of CymaBay and accepted for payment all shares validly tendered and not withdrawn as of the expiration time of the tender offer, and Gilead will promptly pay for such shares, which shares represented approximately 77.3% of CymaBay’s outstanding shares (not including 5,095,996 shares delivered through Notices of Guaranteed Delivery, representing approximately 4.2% of the shares outstanding). Pursuant to the terms of the merger agreement, Purchaser merged with and into CymaBay on March 22, 2024. All outstanding shares of common stock of CymaBay, other than (i) shares owned by Gilead, Purchaser or any of Gilead’s direct or indirect wholly owned subsidiaries, (ii) shares owned by CymaBay, (iii) shares irrevocably accepted by Purchaser for purchase pursuant to the tender offer and (iv) shares held by CymaBay stockholders who properly demand appraisal for their shares under Delaware law, were cancelled and converted into the right to receive cash equal to the $32.50 price per share.

As a result of the completion of the merger, CymaBay has become a wholly owned subsidiary of Gilead and the common stock of CymaBay will no longer be listed for trading on the Nasdaq Global Select Market, which is expected to take effect as of the close of market on March 22, 2024.

This transaction is expected to be accounted for as an asset acquisition and reduce Gilead’s GAAP and non-GAAP 2024 EPS by approximately $3.10 – $3.20. Reflecting acquisition costs, associated operating expenses and lower interest income, we expect this transaction to reduce Gilead’s GAAP and non-GAAP 2024 EPS by approximately $3.35 – $3.45 relative to the full year 2024 guidance shared on February 6, 2024.

Seladelpar is an investigational product that has not been approved for use anywhere globally, and its safety and efficacy have not been established.

Checkpoint Therapeutics Reports Full-Year 2023 Financial Results and Recent Corporate Highlights

On March 22, 2024 Checkpoint Therapeutics, Inc. ("Checkpoint") (Nasdaq: CKPT), a clinical-stage immunotherapy and targeted oncology company, reported financial results for the full-year ended December 31, 2023, and recent corporate highlights (Press release, Checkpoint Therapeutics, MAR 22, 2024, View Source [SID1234641380]).

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James F. Oliviero, President and Chief Executive Officer of Checkpoint, said, "We continue to work closely with our third-party contract manufacturing organization to expeditiously resolve the deficiencies noted in the complete response letter ("CRL") we received last December, and are targeting a Biologics License Application ("BLA") resubmission for cosibelimab by mid-year to potentially obtain marketing approval before the end of 2024. Simultaneously, we continue to execute on a select number of key long lead time commercial launch preparation activities to shorten our launch timeline in anticipation of a potential approval. We remain highly confident in the clinical data and safety package in support of cosibelimab. We look forward to providing additional updates in the second quarter."

2023 and Recent Corporate Highlights:

Checkpoint submitted a BLA to the FDA seeking approval of cosibelimab in January 2023 and the FDA accepted the BLA for filing in March 2023. In December 2023, the FDA issued a CRL for the cosibelimab BLA. The CRL only cited findings that arose during a multi-sponsor inspection of Checkpoint’s third-party contract manufacturing organization as approvability issues to address in a resubmission. The CRL did not state any concerns about the clinical data package, safety, or labeling for the approvability of cosibelimab. Checkpoint intends to address the feedback in a BLA resubmission to potentially enable marketing approval in 2024.
In December 2023, Checkpoint announced that the U.S. Patent and Trademark Office ("USPTO") issued a new patent (U.S. Patent No. 11,834,505) covering a method of treating various cancers, including cutaneous squamous cell carcinoma ("cSCC"), through the administration of cosibelimab. Checkpoint secured U.S. patent protection for cosibelimab through at least May 2038.
In October 2023, Checkpoint announced the publication of results from the multicenter, multiregional, pivotal trial evaluating cosibelimab in patients with metastatic cSCC in the Journal for ImmunoTherapy of Cancer (JITC), the peer-reviewed, online journal of the Society of Immunotherapy of Cancer (SITC) (Free SITC Whitepaper). The paper, entitled, "Efficacy and Safety of Cosibelimab, an Anti–PD-L1 Antibody, in Metastatic Cutaneous Squamous Cell Carcinoma", describes safety and efficacy results from 78 patients with metastatic cSCC enrolled at clinical sites in eight countries.
In July 2023, Checkpoint announced new, longer-term data for cosibelimab from its pivotal studies in locally advanced and metastatic cSCC. These results demonstrate a deepening of response over time, resulting in higher complete response rates than previously reported (55% objective response rate; 26% complete response rate in locally advanced cSCC and 50% objective response rate; 13% complete response rate in metastatic cSCC). Furthermore, responses continue to remain durable over time.
In June 2023, Checkpoint announced that new pharmacokinetic ("PK") modeling data on cosibelimab supporting the extension to an every-three-week dosing regimen were presented at the Population Approach Group Europe 2023 Annual Meeting. Results support comparability of the cosibelimab 800 mg every-two-week and 1200 mg every-three-week dosing regimens.
Throughout 2023 and in January 2024, Checkpoint completed multiple registered direct offerings priced At-the-Market under Nasdaq rules and concurrent private placements of two series of warrants to purchase Checkpoint common stock, for total gross proceeds of approximately $47.6 million. Additionally, in October 2023, Checkpoint announced entry into a definitive agreement for the immediate exercise of warrants for $11.1 million in gross proceeds.
In March 2024, Checkpoint announced the appointment of accomplished life sciences executive, Amit Sharma, M.D., FACP, FASN, FNKF, currently Vice President of Clinical Development and Therapeutic Head for Nephrology and Hematology at Alexion, AstraZeneca Rare Disease, as a non-executive director to Checkpoint’s Board of Directors.
Financial Results:

Cash Position: As of December 31, 2023, Checkpoint’s cash and cash equivalents totaled $4.9 million, compared to $12.1 million at December 31, 2022, a decrease of $7.2 million. This cash position is not reflective of the registered direct offering that closed in January 2024 for total gross proceeds of approximately $14.0 million.
R&D Expenses: Research and development expenses for the year ended December 31, 2023, were $43.6 million, compared to $49.8 million for the year ended December 31, 2022, a decrease of $6.2 million. Research and development expenses for the year ended December 31, 2023 included $4.6 million of non-cash stock expenses, compared to $2.8 million in non-cash stock expenses for the year ended December 31, 2022.
G&A Expenses: General and administrative expenses for both the years ended December 31, 2023 and December 31, 2022, were $8.7 million. General and administrative expenses for the year ended December 31, 2023 included $2.7 million of non-cash stock expenses, compared to $2.5 million in non-cash stock expenses for the year ended December 31, 2022.
Net Loss: Net loss attributable to common stockholders for the year ended December 31, 2023, was $51.8 million, or $3.17 per share, compared to a net loss of $62.6 million, or $7.09 per share, for the year ended December 31, 2022.

BIO-TECHNE RECEIVES EUROPEAN IVDR CERTIFICATION FOR DIAGNOSTIC TEST TO MONITOR CHRONIC MYELOID LEUKEMIA

On March 22, 2024 Bio-Techne Corporation (NASDAQ: TECH) reported that Asuragen, part of Bio-Techne’s Molecular Diagnostics Division, has completed the Class C Certification under the new European Union In Vitro Diagnostic Regulation (IVDR) for its QuantideX qPCR BCR-ABL IS Kit. Previously, the kit was CE-IVD marked for sale in the EU in compliance with the In Vitro Diagnostic Directive (IVDD), which has now been replaced by the IVDR (Press release, Bio-Techne, MAR 22, 2024, View Source [SID1234641379]).

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The QuantideX qPCR BCR-ABL IS Kit gives labs a robust and reliable tool for monitoring chronic myeloid leukemia (CML) patients. The highly sensitive qPCR-based in vitro diagnostic test quantifies BCR-ABL1 and ABL1 transcripts in blood samples from patients with CML to determine their response to tyrosine kinase inhibitor (TKI) therapy. CML patients must undergo regular monitoring to ensure that they continue to receive the most appropriate treatment for their cancer. The QuantideX kit allows for direct reporting on the International Scale and further streamlines the workflow with easy-to-use analysis software. Clinical lab scientists can run up to 49 samples per plate for a scalable solution.

"Bio-Techne is dedicated to quality and compliance, and we applaud this new IVDR for strengthening the safety and performance requirements for diagnostic products," said Matt McManus, President of Bio-Techne’s Diagnostics & Genomics Segment. "We are proud to achieve this new certification and will continue to provide the molecular diagnostic and liquid biopsy solutions that deliver world-class performance, scalability, and reliable results for the laboratory scientists, physicians, and patients who count on us."

Astellas Receives Positive CHMP Opinion for XTANDI™ in Additional Recurrent Early Prostate Cancer Treatment Setting

On March 22, 2024 Astellas Pharma Inc. (TSE: 4503, President and CEO: Naoki Okamura, "Astellas") reported the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion recommending approval of XTANDI (enzalutamide) as monotherapy or in combination with androgen deprivation therapy for the treatment of adult men with high risk biochemical recurrent (BCR) non-metastatic hormone sensitive prostate cancer (nmHSPC) who are unsuitable for salvage radiotherapy (Press release, Astellas, MAR 22, 2024, View Source [SID1234641378]).

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Ahsan Arozullah, MD, MPH, Senior Vice President and Head of Oncology Development, Astellas
"Men with nmHSPC with high-risk biochemical recurrence are very likely to experience disease progression. With approximately 9 out of 10 of these men developing metastatic disease, the need for new and effective treatment options is critical. Today’s positive opinion from the Committee is an important step forward for providing an additional treatment option for these patients and complements the existing efficacy and safety data supporting the use of XTANDI across the prostate cancer disease continuum. We look forward to XTANDI being potentially the first and only androgen receptor signaling inhibitor approved for this patient population in the European Union."

The positive CHMP opinion is based on the results from the Phase 3 EMBARK trial, which were presented as a plenary session during the 2023 American Urological Association Annual Meeting and subsequently published in the New England Journal of Medicine.

The positive opinion will now be reviewed by the European Commission (EC), which has the authority to approve medicines in all 27 European Union (EU) member states as well as Iceland, Liechtenstein and Norway.2

XTANDI was approved by the U.S. Food and Drug Administration (FDA) for the treatment of patients with non-metastatic castration-sensitive prostate cancer (nmCSPC; also known as nmHSPC) with BCR at high risk for metastasis in November 2023. Astellas is also discussing the EMBARK data with other regulatory authorities to support additional license applications for XTANDI in this indication in 2024 and beyond.

Astellas has already reflected the impact from this result in its financial forecast for the current fiscal year ending March 31, 2024.

For more information, please see the press release "European Medicines Agency Validates Type II Variation for Astellas’ XTANDI (enzalutamide) for Treatment of Non-Metastatic Hormone-Sensitive Prostate Cancer with High-Risk Biochemical Recurrence" issued on September 12, 2023.

About EMBARK
The Astellas- and Pfizer-led Phase 3, randomized, double-blind, placebo-controlled, multi-national trial enrolled 1,068 patients with nonmetastatic hormone- (or castration-) sensitive prostate cancer (nmHSPC or nmCSPC) with high-risk BCR at sites in the U.S., Canada, Europe, South America, and the Asia-Pacific region. Patients who were considered to experience high-risk BCR had a prostate-specific antigen doubling time (PSA-DT) ≤ 9 months; serum testosterone ≥ 150 ng/dL (5.2 nmol/L); and screening PSA by the central laboratory ≥ 1 ng/mL if they had a radical prostatectomy (with or without radiotherapy) as primary treatment for prostate cancer, or at least 2 ng/mL above the nadir if they had radiotherapy only as primary treatment for prostate cancer. Patients in the EMBARK trial were randomized to receive enzalutamide 160 mg daily plus leuprolide (n=355), enzalutamide 160 mg as a single agent (n=355), or placebo plus leuprolide (n=358). Leuprolide 22.5 mg was administered every 12 weeks.

EMBARK met its primary endpoint of metastasis-free survival (MFS) for the XTANDI plus leuprolide arm, demonstrating a statistically significant reduction in the risk of metastasis or death over placebo plus leuprolide. MFS is defined as the duration of time in months between randomization and the earliest objective evidence of radiographic progression by central imaging or death due to any cause, whichever occurred first.

The study also met a key secondary endpoint, by demonstrating that patients treated with XTANDI (single agent) had a statistically significant reduction in the risk of metastasis or death versus placebo plus leuprolide, meeting its MFS endpoint.

In EMBARK, Grade 3 or higher adverse events (AEs) were reported in 46% of XTANDI plus leuprolide patients, 50% of patients treated with XTANDI (single agent), and 43% of patients receiving placebo plus leuprolide. Permanent discontinuation due to AEs as the primary reason was reported in 21% of XTANDI plus leuprolide patients, 18% in XTANDI (single agent) patients, and 10% in placebo plus leuprolide patients.

For more information on the EMBARK trial (NCT02319837) go to www.clinicaltrials.gov.

About High Risk Biochemical Recurrent Non-Metastatic Hormone Sensitive Prostate Cancer
In non-metastatic hormone (or castration-) sensitive prostate cancer (nmHSPC or nmCSPC), no evidence of the cancer spreading to distant parts of the body (metastases) is detectable with conventional radiological methods (CT/MRI), and the cancer still responds to medical or surgical treatment designed to lower testosterone levels.3,4 Of men who have undergone definitive prostate cancer treatment, including radical prostatectomy, radiotherapy, or both, an estimated 20-40% will experience a BCR within 10 years.5 About 9 out of 10 men with high-risk BCR will develop metastatic disease, and 1 in 3 will die as a result of their metastatic prostate cancer.3 The EMBARK trial focused on men with high-risk BCR. Per the EMBARK protocol, patients with nmHSPC and high-risk BCR are those initially treated by radical prostatectomy or radiotherapy, or both, with a PSA-DT ≤ 9 months. High-risk BCR patients with a PSA-DT of ≤ 9 months have a higher risk of metastases and death.6

About XTANDI (enzalutamide)
XTANDI (enzalutamide) is an androgen receptor signaling inhibitor. XTANDI is a standard of care and has received regulatory approvals in one or more countries around the world for use in men with metastatic hormone-sensitive prostate cancer (mHSPC), metastatic castration-resistant prostate cancer (mCRPC), non-metastatic castration-resistant prostate cancer (nmCRPC) and non-metastatic hormone-sensitive prostate cancer (nmHSPC) with high-risk biochemical recurrence (BCR). XTANDI is currently approved for one or more of these indications in more than 90 countries, including in the United States, European Union and Japan. Over one million patients have been treated with XTANDI globally.7

About XTANDI (enzalutamide) in the E.U.
Enzalutamide is an androgen receptor signaling inhibitor indicated in the E.U. for the treatment of adult men with:

Metastatic hormone-sensitive prostate cancer (mHSPC, also known as metastatic castration-sensitive prostate cancer or mCSPC) in combination with androgen deprivation therapy (ADT).
High-risk non-metastatic castration-resistant prostate cancer (CRPC).
Metastatic CRPC who are asymptomatic or mildly symptomatic after failure of ADT in whom chemotherapy is not yet clinically indicated. It is also indicated in adult men with metastatic CRPC whose disease has progressed on or after docetaxel therapy.
Important Safety Information
For important Safety Information for enzalutamide please see the full Summary of Product Characteristics at: View Source

Important Safety Information
For Important Safety Information for enzalutamide please see the Package Insert.

FENNEC PHARMACEUTICALS REPORTS FULL YEAR AND FOURTH QUARTER 2023 FINANCIAL RESULTS AND PROVIDES BUSINESS UPDATE

On March 21, 2024 Fennec Pharmaceuticals Inc. (NASDAQ:FENC; TSX: FRX), a specialty pharmaceutical company, reported its financial results for the fiscal year ended December 31, 2023 and provided a business update (Press release, Fennec Pharmaceuticals, MAR 21, 2024, View Source [SID1234641408]).

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"It was an exciting year for Fennec given the strong performance with PEDMARK in the first full fiscal year following its U.S. commercial launch. We are pleased with our execution against strategic plans and our momentum in 2023, which sets the stage for further success in 2024 and beyond. We also received European Commission and U.K. approvals of PEDMARQSI, which led to the recent announcement of an exclusive licensing agreement with Norgine for Europe, Australia and New Zealand," said Rosty Raykov, Chief Executive Officer of Fennec Pharmaceuticals. "We have significantly strengthened our balance sheet through the agreement with Norgine, and we remain dedicated to further growing our revenues as we expand the availability of PEDMARK to patients and providers globally."

Recent Developments and Highlights:

· Entered into exclusive licensing agreement to commercialize PEDMARQSI in Europe, Australia and New Zealand. Fennec received approximately $43 million upfront and has the potential to receive up to approximately $230 million in additional commercial and regulatory milestones, and double-digit tiered royalties up to the mid-twenties. PEDMARQSI was granted EU marketing authorization by the European Commission in June 2023, and received UK approval from the MHRA in October 2023.

· Achieved PEDMARK net product revenue of approximately $9 million and $21 million for the fourth quarter and full year 2023, respectively. Additionally, anticipate continued increasing utilization of the earlier endorsement from the NCCN for PEDMARK in the adolescent and young adult (AYA) population.

· In January 2024, the FDA issued a public reminder to healthcare providers that PEDMARK (sodium thiosulfate injection) is not substitutable with other sodium thiosulfate products as explicitly directed in its prescribing label.

Financial Results for the Fourth Quarter and Fiscal Year Ended December 31, 2023

· Net Sales – Net product sales of $21.3 million in fiscal 2023 compared to $1.5 million in 2022. The Company had gross profit of $20.0 million for fiscal year ended 2023. The increase in sales reflects strong growth in new patient starts and accounts.

· Cash Position – Cash and cash equivalents were $13.2 million as of December 31, 2023. There was a $10.5 million decrease in cash and cash equivalents between December 31, 2023 and December 31, 2022 as a result of cash outlays for operating expenses related to the promotion and marketing of PEDMARK, general and administrative expenses and the preparation for the commercial launch of PEDMARQSI in Europe. These cash outflows were offset by cash inflows primarily from product sales. In addition, as announced this week, we received approximately $43 million from the licensing of Europe, Australia and New Zealand to Norgine. Inclusive of these events, the pro forma December 31, 2023 cash balance is in excess of $55 million. We anticipate that our cash, cash equivalents and investment securities as of December 31, 2023, when coupled with PEDMARK revenue assumptions and the recently announced license agreement for Europe, will be sufficient to fund our planned operations for at least the next twelve months.

· Research and Development Expenses (R&D) Expenses – R&D expenses decreased by $3.5 million in fiscal 2023 as compared to fiscal 2022. The Company reduced research and development costs when it received FDA approval of PEDMARK in September 2022. The majority of traditional research and development expenses associated with PEDMARK are now recorded as general and administrative expenses or capitalized into inventory and eventually recorded to costs of product sales.

· Selling and Marketing Expenses – Selling and marketing expenses include remuneration of our sales and marketing employees, dollars spent on marketing campaigns (sponsorships, trade shows, presentations, etc.), and any activities to support marketing and sales activities. The Company recorded $12.1 million in selling and marketing expenses in fiscal 2023, compared to $2.8 million in fiscal year 2022.

· General and Administrative (G&A) Expenses – For fiscal 2023, G&A expenses increased by $2.3 million compared to fiscal 2022. Non-cash expenses associated with equity remuneration increased by $1.4 million in fiscal year 2023 over 2022. Payroll and benefits related expenses rose by $1.1 million in fiscal 2023 compared to fiscal 2022. There was an increase in consulting and professional costs of $0.8 million in fiscal 2023 over fiscal 2022.

· Net Loss – Net losses for the fourth quarter and year ended December 31, 2023, of $2.7 million ($0.10 per share) and $16.0 million ($0.60 per share), respectively, compared to $6.9 million ($0.26 per share) and $23.7 million ($0.90 per share), respectively, for the same periods in 2022.

Financial Update

The selected financial data presented below is derived from our unaudited, condensed consolidated financial statements, which were prepared in accordance with U.S. generally accepted accounting principles. The complete audited, condensed consolidated financial statements for the period ended December 31, 2023, and management’s discussion and analysis of financial condition and results of operations, will be available via www.sec.gov and www.sedar.com. All values are presented in thousands unless otherwise noted.

Audited Consolidated

Statements of Operations:

(U.S. Dollars in thousands except per share amounts)

Three Months Ended Twelve Months Ended
December 31, December 31, December 31, December 31,
2023 2022 2023 2022
Revenue
PEDMARK product sales, net $ 9,735 $ 1,535 $ 21,252 $ 1,535
Cost of products sold (685 ) (86 ) (1,259 ) (86 )
Gross profit 9,050 1,449 19,993 1,449

Operating expenses:
Research and development 32 117 56 3,531
Selling and marketing 3,868 2,785 12,123 2,785
General and administrative 6,968 4,682 20,585 17,722

Total operating expenses 10,868 7,584 32,764 24,038
Loss from operations (1,818 ) (6,135 ) (12,771 ) (22,589 )

Other (expense)/income
Unrealized foreign exchange gain (loss) 2 (58 ) 5 (9 )
Amortization expense (70 ) (70 ) (287 ) (149 )
Unrealized gain (loss) on securities 4 (3 ) (39 ) (184 )
Interest income 115 153 441 195
Interest expense (915 ) (744 ) (3,394 ) (978 )
Total other (expense)/income (864 ) (722 ) (3,274 ) (1,125 )

Net loss $ (2,682 ) $ (6,857 ) $ (16,045 ) $ (23,714 )

Basic net loss per common share $ (0.10 ) $ (0.26 ) $ (0.60 ) $ (0.90 )
Diluted net loss per common share $ (0.10 ) $ (0.26 ) $ (0.60 ) $ (0.90 )
Weighted-average number of common shares outstanding, basic 26,833 26,275 26,574 26,275
Weighted-average number of common shares outstanding, diluted 26,833 26,275 26,574 26,275

Audited Consolidated Balance Sheets:

(U.S. Dollars in thousands)

December 31, December 31,
2023 2022
Assets

Current assets
Cash and cash equivalents $ 13,269 $ 23,774
Accounts receivable, net 8,814 1,545
Prepaid expenses 583 770
Inventory 2,156 576
Other current assets 21 63
Total current assets 24,843 26,728

Non-current assets
Deferred issuance cost, net amortization 2,021 211
Total non-current assets 2,021 211
Total assets $ 26,864 $ 26,939

Liabilities and shareholders’ (deficit) equity

Current liabilities:
Accounts payable $ 3,799 $ 2,390
Accrued liabilities 3,754 2,219
Total current liabilities 7,553 4,609

Long term liabilities
Term loan 30,000 25,000
PIK interest 1,219 260
Debt discount (286 ) (361 )
Total long term liabilities 30,933 24,899
Total liabilities 38,486 29,508

Commitments and Contingencies

Shareholders’(deficit) equity:
Common stock, no par value; unlimited shares authorized; 26,361 shares issued and outstanding (2022 -26,014) 144,307 142,591
Additional paid-in capital 60,073 56,797
Accumulated deficit (219,245 ) (203,200 )
Accumulated other comprehensive income 1,243 1,243
Total shareholders’ (deficit) equity (11,622 ) (2,569 )
Total liabilities and shareholders’ (deficit) equity $ 26,864 $ 26,939

Fiscal Year Ended
Working capital
Selected Asset and Liability Data: December 31,
2023 December 31,
2022
(U.S. Dollars in thousands)
Cash and equivalents $ 13,269 $ 23,774
Other current assets 11,574 2,954
Current liabilities (7,553 ) (4,608 )
Working capital $ 17,290 $ 22,120

Selected Equity:
Common stock and additional paid in capital 206,380 199,388
Accumulated deficit (219,245 ) (203,200 )
Shareholders’ equity (11,622 ) (2,569 )

About Cisplatin-Induced Ototoxicity

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

The incidence of ototoxicity depends upon the dose and duration of chemotherapy, and many of these children require lifelong hearing aids or cochlear implants, which can be helpful for some, but do not reverse the hearing loss and can be costly over time.ii Infants and young children that are affected by ototoxicity at critical stages of development lack speech and language development and literacy, and older children and adolescents often lack social-emotional development and educational achievement.iii

PEDMARK (sodium thiosulfate injection)

PEDMARK is the first and only U.S. Food and Drug Administration (FDA) approved therapy indicated to reduce the risk of ototoxicity associated with cisplatin treatment in pediatric patients with localized, non-metastatic, solid tumors. It is a unique formulation of sodium thiosulfate in single-dose, ready-to-use vials for intravenous use in pediatric patients.7 PEDMARK is also the only therapeutic agent with proven efficacy and safety data with an established dosing paradigm, across two open-label, randomized Phase 3 clinical studies, the Clinical Oncology Group (COG) Protocol ACCL0431 and SIOPEL 6.

In the U.S. and Europe, it is estimated that, annually, more than 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 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 co-operative groups in two Phase 3 clinical studies of survival and reduction of ototoxicity, COG ACCL0431 and SIOPEL 6. Both studies have been completed. The COG ACCL0431 protocol enrolled childhood cancers typically treated with intensive cisplatin therapy for localized and disseminated disease, including newly diagnosed hepatoblastoma, germ cell tumor, osteosarcoma, neuroblastoma, medulloblastoma, and other solid tumors. SIOPEL 6 enrolled only hepatoblastoma patients with localized tumors.

Indications and Usage

PEDMARK (sodium thiosulfate injection) is indicated to reduce the risk of ototoxicity associated with cisplatin in pediatric patients 1 month of age and older with localized, non-metastatic solid tumors.

Limitations of Use

The safety and efficacy of PEDMARK have not been established when administered following cisplatin infusions longer than 6 hours. PEDMARK may not reduce the risk of ototoxicity when administered following longer cisplatin infusions, because irreversible ototoxicity may have already occurred.

Important Safety Information

PEDMARK is contraindicated in patients with history of a severe hypersensitivity to sodium thiosulfate or any of its components.

Hypersensitivity reactions occurred in 8% to 13% of patients in clinical trials. Monitor patients for hypersensitivity reactions. Immediately discontinue PEDMARK and institute appropriate care if a hypersensitivity reaction occurs. Administer antihistamines or glucocorticoids (if appropriate) before each subsequent administration of PEDMARK. PEDMARK may contain sodium sulfite; patients with sulfite sensitivity may have hypersensitivity reactions, including anaphylactic symptoms and life-threatening or severe asthma episodes. Sulfite sensitivity is seen more frequently in people with asthma.

PEDMARK is not indicated for use in pediatric patients less than 1 month of age due to the increased risk of hypernatremia or in pediatric patients with metastatic cancers.

Hypernatremia occurred in 12% to 26% of patients in clinical trials, including a single Grade 3 case. Hypokalemia occurred in 15% to 27% of patients in clinical trials, with Grade 3 or 4 occurring in 9% to 27% of patients. Monitor serum sodium and potassium levels at baseline and as clinically indicated. Withhold PEDMARK in patients with baseline serum sodium greater than 145 mmol/L.

Monitor for signs and symptoms of hypernatremia and hypokalemia more closely if the glomerular filtration rate (GFR) falls below 60 mL/min/1.73m2.

Administer antiemetics prior to each PEDMARK administration. Provide additional antiemetics and supportive care as appropriate.

The most common adverse reactions (≥25% with difference between arms of >5% compared to cisplatin alone) in SIOPEL 6 were vomiting, nausea, decreased hemoglobin, and hypernatremia. The most common adverse reaction (≥25% with difference between arms of >5% compared to cisplatin alone) in COG ACCL0431 was hypokalemia.

Please see full Prescribing Information for PEDMARK at: www.PEDMARK.com.