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.

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."

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.

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.

On March 21, 2024 Innate Pharma SA (Euronext Paris: IPH; Nasdaq: IPHA) ("Innate" or the "Company") reported its consolidated financial results for the year ending December 31, 2023 (Press release, Innate Pharma, MAR 21, 2024, View Source [SID1234641366]). The consolidated financial statements are attached to this press release.

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"We ended 2023 with a cash runway to the end of 2025 and achieved significant milestones in advancing our pipeline," said Hervé Brailly, Chief Executive Officer ad interim of Innate Pharma. "We reported positive data with lacutamab in Sézary syndrome, began Phase 1 testing of our proprietary, second-generation ANKET IPH6501 and secured further validation of our ANKET platform with Sanofi having licensed four ANKET candidates for hematologic malignancies and solid tumors. The Phase 3 trial for monalizumab in non-small lung cancer that is being led by Astra Zeneca continues to advance. Looking ahead to 2024, we expect notable milestones including final results from the TELLOMAK Phase 2 trial with lacutamab in mycosis fungoides, and progressing our first proprietary ADC program, IPH45 towards an IND filing."

Pipeline highlights:

Lacutamab (anti-KIR3DL2 antibody):

Cutaneous T Cell lymphoma

Innate reported positive final data from the Phase 2 TELLOMAK study in Sézary syndrome at the American Society of Hematology (ASH) (Free ASH Whitepaper) 2023 Annual Congress. Data demonstrate that lacutamab showed robust clinical activity and an overall favorable safety profile. In this heavily pre-treated population, post-mogamulizumab, with a median of five prior lines of therapy, the global confirmed objective response rate (ORR) was 37.5% (21/56). Confirmed ORR in the skin was 46.4% (26/56) and confirmed ORR in the blood was 48.2% (27/56). Median progression-free survival was 8.0 months (95% confidence interval [CI] 4.7-21.2).
In 2023, Innate reported interim data with lacutamab in mycosis fungoides (MF) patients at the EORTC Cutaneous Lymphoma Tumour Group Annual Meeting (September 2023) and the 17th International Conference on Malignant Lymphoma (June 2023). The interim data set confirmed clinical activity and favorable safety profile of lacutamab in line with the Phase 1 data.
The top-line results in MF patients are currently being analyzed and Innate intends to present the data in 2024 at a medical conference.
In January 2024, Innate announced that the US Food and Drug Administration (FDA) has lifted the partial clinical hold previously placed on the lacutamab IND on October 2023 following a patient death in the TELLOMAK study. The FDA decision to lift the partial clinical hold is based on the FDA review of the fatal case which Innate, together with a steering committee of independent experts, determined to be related to aggressive disease progression and lacutamab unrelated.
Peripheral T Cell lymphoma (PTCL)

Despite objective responses observed, the Company-sponsored Phase 1b clinical trial evaluating lacutamab as monotherapy in patients with KIR3DL2-expressing refractory/relapsing PTCL will not be reopened to recruitment as the prespecified threshold for meaningful clinical activity was not reached.
At the ASH (Free ASH Whitepaper) Annual Congress 2023, Innate presented a poster with preclinical data demonstrating a synergistic effect between lacutamab and chemotherapy in preclinical models of PTCL, supporting the rationale for combination strategy in this clinical indication.
The Phase 2 KILT (anti-KIR in T Cell Lymphoma) trial, an investigator-sponsored, randomized trial led by the Lymphoma Study Association (LYSA) to evaluate lacutamab in combination with chemotherapy GEMOX (gemcitabine in combination with oxaliplatin) versus GEMOX alone in patients with KIR3DL2-expressing relapsed/refractory PTCL is ongoing.
ANKET (Antibody-based NK cell Engager Therapeutics):

ANKET is Innate’s proprietary platform for developing next-generation, multi-specific NK cell engagers to treat certain types of cancer. Innate’s pipeline includes five public drug candidates born from the ANKET platform: SAR443579 (SAR’579/IPH6101) (CD123-targeted), SAR445514 (SAR’514/IPH6401) (BCMA-targeted), IPH62 (B7-H3-targeted), IPH67 (target undisclosed, solid tumors) and tetra-specific IPH6501 (CD20-targeted with IL-2v). Several other undisclosed proprietary preclinical targets are being explored.

SAR’579, SAR’514, IPH62 and IPH67 (partnered with Sanofi)

SAR443579/IPH6101

The Phase 1/2 clinical trial by Sanofi is progressing well, evaluating SAR443579 / IPH6101, a trifunctional anti-CD123 NKp46×CD16 NK cell engager and ANKET platform lead asset, in patients with relapsed or refractory acute myeloid leukemia (R/R AML), B-cell acute lymphoblastic leukemia (B-ALL) or high-risk myelodysplastic syndrome (HR-MDS).
At the ASH (Free ASH Whitepaper) Annual Congress 2023, Sanofi reported updated efficacy and safety results and data across all dose levels tested for SAR443579. As of October 23, 2023, 43 patients (42 R/R AML and 1 HR-MDS) across 8 Dose Levels (DLs) at 10 – 6000 μg/kg/dose were included. Patients had received a median of 2.0 (1.0 – 10.0) prior lines of treatment with 13 patients (30.2%) reporting prior hematopoietic stem cell transplantation and 36 patients (83.7%) with prior exposure to venetoclax. In DLs with a highest dose of 1000 μg/kg QW, 5/15 AML (33.3%) patients achieved a CR (4 CR / 1 CRi) as of the cut-off date. As of the data cut-off on October 23, 2023, two responders remain in remission after more than 12 and 14 months of treatment. SAR443579 was well tolerated up to doses of 6000 μg/kg QW with observed clinical benefit in patients with R/R AML. The results are consistent with the predicted favorable safety profile.
Preliminary Pharmacokinetics (PK) and Pharmacodynamic (PD) Analysis of the CD123 NK Cell Engager SAR’579/IPH6101 in patients with relapsed or refractory AML, B-ALL or HR-MDS were presented during the ESMO (Free ESMO Whitepaper) (European Society for Medical Oncology) Congress 2023.
The U.S. Food and Drug Administration (FDA) has granted Fast Track Designation for SAR’579 / IPH6101 for the treatment of acute myeloid leukemia.
SAR’514/IPH6401

The Phase 1/2 clinical trial with SAR’514 / IPH6401, a trifunctional anti-BCMA Nkp46xCD16 NK cell engager, led by Sanofi, in patients with Relapsed/Refractory Multiple Myeloma and Relapsed/Refractory Light-chain Amyloidosis is ongoing.
IPH62

As announced on December 19, 2022, Sanofi licensed IPH62, a NK cell engager program targeting B7-H3 from Innate’s ANKET platform. Upon candidate selection, Sanofi will be responsible for all development, manufacturing and commercialization. Under the terms of the research collaboration and license agreement signed in December 2022, Innate received a €25m upfront payment and is eligible for up to €1.35bn total in preclinical, clinical, regulatory and commercial milestones plus royalties on potential net sales.
IPH67

In December 2023, Sanofi exercised its option to license a NK cell engager program in solid tumors from Innate’s ANKET platform pursuant to the terms of the research collaboration and license agreement signed in December 2022. Following a research collaboration period, Sanofi will be responsible for all development, manufacturing and commercialization. Sanofi still retains the option to one additional ANKET target. Innate received a €15m payment as option exercise.
IPH6501 (proprietary)

In March 2024 the first patient was dosed in the Phase 1/2 clinical trial evaluating IPH6501, Innate’s proprietary CD20-targeted IL-2v bearing second-generation ANKET in B cell Non-Hodgkin’s lymphoma (B-NHL). The study is ongoing and planned to enroll up to 184 patients.
Innate presented preclinical data on IPH6501 at the European Hematology Association (EHA) (Free EHA Whitepaper) 2023 congress. In preclinical settings, IPH6501 was shown to induce NK cell proliferation and to trigger high NK cell cytotoxicity against CD20+ target cells in in vitro assays, in ex vivo assays with relapse/refractory (R/R) B-NHL patient samples who received at least one prior treatment, as well as in in vivo studies in non-human primates. A surrogate of IPH6501 mediated a potent anti-tumor activity in vivo in CD20+ tumor models in mice. In addition, in ex vivo assays with R/R B-NHL patient samples, IPH6501 was shown to be more efficient than a T-cell engager targeting CD20.
Monalizumab (anti-NKG2A antibody), partnered with AstraZeneca:

The Phase 3 PACIFIC-9 trial run by AstraZeneca evaluating durvalumab (anti-PD-L1) in combination with monalizumab or AstraZeneca’s oleclumab (anti-CD73) in patients with unresectable, Stage III non-small cell lung cancer (NSCLC) who have not progressed following definitive platinum-based concurrent chemoradiation therapy (CRT) is ongoing.
IPH5201 (anti-CD39), partnered with AstraZeneca:

The MATISSE Phase 2 clinical trial conducted by Innate in neoadjuvant lung cancer for IPH5201, an anti-CD39 blocking monoclonal antibody developed in collaboration with AstraZeneca, is ongoing and recruitment is on track.
IPH5301 (anti-CD73):

The investigator-sponsored CHANCES Phase 1 trial of IPH5301 by Institut Paoli-Calmettes is ongoing.
Antibody Drug Conjugates:

Fueling its R&D pipeline, Innate continues to develop different approaches for the treatment of cancer utilizing its antibody engineering capabilities to deliver novel assets, with its innovative ANKET platform and exploring Antibody Drug Conjugates (ADC) formats. Beyond its proprietary programs, Innate has an ongoing agreement with Takeda on ADCs.
IPH45 (Nectin-4 ADC):

IPH45 is Innate’s proprietary Nectin-4 targeting antibody drug conjugate including a Topoisomerase I inhibitor payload. IPH45 continues towards IND filing this year.
Innate will share first preclinical data with IPH45 in an oral presentation at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) 2024.
Takeda license agreement:

In April 2023, Innate announced that it has entered into an exclusive license agreement with Takeda under which Innate grants Takeda exclusive worldwide rights to research and develop antibody drug conjugates (ADC) using a panel of selected Innate antibodies against an undisclosed target, with a primary focus in Celiac disease. Under the terms of the license agreement, Innate received a $5m upfront payment and is eligible to receive up to $410m in future development, regulatory and commercial milestones if all milestones are achieved during the term of the agreement, plus royalties on potential net sales of any commercial product resulting from the license.
Corporate Update:

On April 26, 2023, Innate announced the establishment of an At-The-Market (ATM) program, pursuant to which it may, from time to time, offer and sell to eligible investors a total gross amount of up to $75 million American Depositary Shares ("ADS"). Each ADS representing one ordinary share of Innate. As of December 31, 2023, the balance available under our April 2023 sales agreement remains at $75 million.
Dr. Sonia Quaratino, MD, PhD, has been appointed as Executive Vice President and Chief Medical Officer of Innate Pharma, effective October 2023.
On December 18, 2023, Innate announced that Mondher Mahjoubi has resigned from his position as Chief Executive Officer (CEO) and Chairman of the Executive Board of the Company, effective as of January 2024. Hervé Brailly, Innate Pharma’s Chairman of the Supervisory Board, former CEO and co-founder was appointed as interim CEO and Chairman of the Executive Board while a permanent successor is sought.
Irina Staatz-Granzer, who has been Vice-Chairwoman of the Supervisory Board for several years was appointed Chairwoman of the Supervisory Board.
Post period event

Early January 2024, Innate announced that it has strengthened the Company’s leadership and corporate governance with the appointment of two new Executive Board members. Arvind Sood, Executive Vice President (EVP), President of US Operations, Dr Sonia Quaratino, EVP, Chief Medical Officer, joining Hervé Brailly, interim Chief Executive Officer and Yannis Morel, EVP, appointed Chief Operating Officer.
Innate announced that Arvind Sood had joined the Company in a newly created position of Executive Vice President and President of US Operations.
Financial highlights for 2023:

The key elements of Innate’s financial position and financial results as of and for the year ended December 31, 2023 are as follows:

Cash, cash equivalents, short-term investments and financial assets amounting to €102.3 million (€m) as of December 31, 2023 (€136.6m as of December 31, 2022), including financial instruments amounting to €9.8m (€35.1m as of December 31, 2022). Cash, cash equivalents as of December 31, 2023 do not include the €15.0 million payment made by Sanofi following the exercise of the license option announced in December 2023. This amount was received by the Company in January 2024.
As of December 31, 2023, financial liabilities amount to €39.9m (€42.3m as of December 31, 2022). This change is mainly due to loan repayments.
Revenue and other income from continuing operations amounted to €61.6m in 2023 (2022: €57.7m, +6.9%). It mainly comprises revenue from collaboration and licensing agreements (€51.9m in 2023 vs €49.6m in 2022, +4.7%), and research tax credit (€9.7m in 2023 vs €7.9m in 2022, +22.8%):
Revenue from collaboration and licensing agreements, which mainly resulted from the partial or entire recognition of the proceeds received pursuant to the agreements with AstraZeneca, Sanofi and Takeda. They results from the partial or entire recognition of the proceeds received pursuant to the agreements with AstraZeneca, Sanofi and Takeda. They are recognized when the entity’s performance obligation is met. Their accounting is made at a point in time or spread over time according to the percentage of completion of the work that the Company is committed to carry out under these agreements:
(i) Revenue from collaboration and licensing agreements for monalizumab decreased by €12.9m to €9.5m in 2023 ( €22.4m in 2022). This change mainly results from the transaction price increase of €13.4m ($14.0m), in the first half of 2022, triggered by the launch of the "PACIFIC-9" Phase 3 trial announced on April 29, 2022. As a reminder, this increase in the transaction price generated a €12.6 million favorable cumulative adjustment in the revenue related to monalizumab agreements as of December 31,2022;
(ii) Revenue related to the research collaboration and licensing agreement signed with Sanofi in 2022 amounted €34.7m as of December 31, 2023. On January 25, 2023, the Company announced the expiration of the waiting period under the Hart-Scott-Rodino (HSR) Antitrust Improvements Act of 1976 and the effectiveness of the licensing agreement as of January 24, 2023. Consequently, the Company received an upfront payment of €25.0m in March 2023, including €18.5m for the exclusive license, €1.5m for the research work and €5.0m for the two additional targets options, for which the Company will recognize the related revenues either at the reporting date or three years after the effective date. The €18.5m upfront payment relating to the exclusive license has been fully recognized in revenue since June 30, 2023. On December 19, 2023, the Company announced that Sanofi had exercised one of the two license options for a new program based on the Company’s ANKET platform. This decision triggered a milestone payment of €15.0m, including €13.3m for the exclusive license, fully recognized in revenue as of December 31, 2023, and €1.7m for research work to be carried out by the Company as well as the recognition in revenue of an amount of €2.5m initially received in March 2023 in connection with this option;
(iii) Revenue related to the license and collaboration agreement signed with Sanofi in 2016 decreased by €2.0m, to €2.0m for year ended December 31, 2023, as compared to €4.0m for year ended December 31, 2022. The Company announced that, in June 2023, the first patient was dosed in a Sanofi-sponsored Phase 1/2 clinical trial evaluating SAR’514/IPH6401 in relapsed or refractory Multiple Myeloma. As provided by the licensing agreement signed in 2016, Sanofi made a milestone payment of €2.0 million, fully recognized in revenue since of June 30, 2023. This amount was received by the Company on July 21, 2023. As a reminder, the revenue recognized 2022 mainly resulted from Sanofi’s decision to advance SAR’514/IPH6401 into investigational new drug (IND)- enabling studies. This decision triggered a €3.0 million milestone payment from Sanofi to the Company, fully recognized in revenue as of June 30, 2022;
(iv) Revenue related to the licensing agreement signed with Takeda in 2023 amounted €4.6m for year ended December 31, 2023. On April 3, 2023, the Company announced that it has entered into an exclusive license agreement with Takeda under which Innate grants Takeda exclusive worldwide rights to research and develop antibody drug conjugates (ADC) using a panel of selected Innate antibodies against an undisclosed target, with a primary focus in Celiac disease. Takeda will be responsible for the future development, manufacture and commercialization of any potential products developed using the licensed antibodies. As such, the Company considers that the license granted is a right to use the intellectual property, which is granted fully and perpetually to Takeda. The agreement does not stipulate that Innate’s activities will significantly affect the intellectual property granted during the life of the agreement. Consequently, the $5.0m (or €4.6m) initial payment, received by the Company in May 2023, was fully recognized in revenue since June 30, 2023.
The research tax credit (CIR) of €9.7m of as December 31, 2023 (€7.9m for year ended December 31 December, 2022, including 2022 fiscal year CIR for an amount of €9.2 million reduced by €1.3 million related to a provision following the tax inspection carried out in 2022 by the French tax authorities).
Operating expenses from continuing operations and before impairment amounted to €74.3m in 2023 (2022: €74.1m, +0.3%):
General and administrative (G&A) expenses from continuing activities amounted to €18.3m in 2023 (2022: €22.4m, -18.5%). This variation results cumulatively from (i) a reduction in personnel expenses, (ii) a reduction in non-scientific fees, (iii) the pursuit of cost savings (reduction in office space), (iv) a reclassification of expenses relating to the support of R&D laboratory activities (maintenance, depreciation of R&D equipment) in the amount of €1.0 million.
Research and development (R&D) expenses from continuing activities amounted to €56.0m in 2023 (2022: €51.7m, +8.4%). This change was mainly due to an increase in direct research and development expenses, notably for non-clinical development programs, partially offset by a decrease in expenses for clinical programs over the period. Indirect research and development expenses increased, mainly in the fields of personnel costs and depreciation, amortization and impairment.
As a reminder, as of December 31, 2022, the Company recognized the full impairment of the avdoralimab intangible asset (anti-C5aR rights) for an amount of €41,0m (non-cash expense) following the Company’s decision to stop avdoralimab development in bullous pemphigoid indication in inflammation.
A net financial income of €5.1m in 2023 (2022: €0.5m loss).
Net income from Lumoxiti discontinued operations are nil for year ended December 31, 2023 as compared to a net loss of €0.1m for year ended December 31, 2022 corresponding to residual costs associated with the transfer of activities to AstraZeneca. This transfer has now been completed.
A net loss of €7.6m in 2023 (2022: net loss of €58.1m).
The table below summarizes the IFRS consolidated financial statements as of and for the year ended December 31, 2023, including 2022 comparative information.

In thousands of euros, except for data per share

December 31, 2023

December 31, 2022

Revenue and other income

61,641

57,674

Research and development

(56,022)

(51,663)

Selling, general and administrative

(18,288)

(22,436)

Total operating expenses

(74,310)

(74,099)

Operating income (loss) before impairment

(12,669)

(57,425)

Impairment of intangible asset

—

(41,000)

Operating income (loss) after impairment

(12,669)

(57,425)

Net financial income (loss)

5,099

(546)

Income tax expense

—

—

Net income (loss) from continuing operations

(7,570)

(57,972)

Net income (loss) from discontinued operations

—

(131)

Net income (loss)

(7,570)

(58,103)

Weighted average number of shares outstanding (in thousands)

80,453

79,640

Basic income (loss) per share

(0.09)

(0.73)

Diluted income (loss) per share

(0.09)

(0.73)

Basic income (loss) per share from continuing operations

(0.09)

(0.73)

Diluted income (loss) per share from continuing operations

(0.09)

(0.73)

Basic income (loss) per share from discontinued operations

—

—

Diluted income (loss) per share from discontinued operations

—

—

December 31, 2023

December 31, 2021

Cash, cash equivalents and financial asset

102,252

136,604

Total assets

184,193

207,863

Shareholders’ equity

51,901

54,151

Total financial debt

39,893

42,251