On August 6, 2024 Exelixis, Inc. (Nasdaq: EXEL) reported that its supplemental New Drug Application (sNDA) for cabozantinib (CABOMETYX) has been accepted in the U.S. for: 1) the treatment of adults with previously treated, locally advanced/unresectable or metastatic, well- or moderately differentiated pancreatic neuroendocrine tumors (pNET), and 2) the treatment of adults with previously treated, locally advanced/unresectable or metastatic, well- or moderately differentiated extra-pancreatic NET (epNET) (Press release, Exelixis, AUG 6, 2024, View Source [SID1234645418]). The U.S. Food and Drug Administration (FDA) also granted orphan drug designation to cabozantinib for the treatment of pNET. The FDA assigned a standard review with a Prescription Drug User Fee Act target action date of April 3, 2025.

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"The FDA’s acceptance of this application marks another important milestone in our commitment to bringing cabozantinib to patients living with difficult-to-treat cancers and who have limited treatment options," said Amy Peterson, M.D., Executive Vice President, Product Development & Medical Affairs, and Chief Medical Officer, Exelixis. "We appreciate the opportunity to work with the FDA in the coming months as they review our application, with the goal to bring this new, effective treatment option to patients with advanced neuroendocrine tumors as quickly as possible."

The sNDA is based on the final results of the phase 3 CABINET pivotal trial evaluating cabozantinib compared with placebo in two cohorts of patients with previously treated NET: advanced pNET and advanced epNET. As previously announced, CABINET was stopped early for compelling activity; all patients were unblinded and those on placebo were given the option to cross over to active treatment with cabozantinib. This early stopping was due to a dramatic improvement in progression-free survival (PFS) observed at an interim analysis in both cohorts. The study demonstrated a statistically significant and clinically meaningful improvement in PFS with cabozantinib versus placebo, based on results of both local review and available independent blinded central radiology review. Initial results were presented at the 2023 European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress; final results will be presented at the 2024 ESMO (Free ESMO Whitepaper) Congress on September 16th in Barcelona, Spain.

About CABINET (Alliance A021602)
CABINET (Randomized, Double-Blinded Phase III Study of CABozantinib versus Placebo In Patients with Advanced NEuroendocrine Tumors After Progression on Prior Therapy) is sponsored by the National Cancer Institute (NCI), part of the National Institutes of Health, and is being led and conducted by the NCI-funded Alliance for Clinical Trials in Oncology with participation from the NCI-funded National Clinical Trials Network as part of Exelixis’ collaboration through a Cooperative Research and Development Agreement with the NCI’s Cancer Therapy Evaluation Program.

CABINET is a multicenter, randomized, double-blinded, placebo-controlled phase 3 pivotal trial that had enrolled a total of 290 patients in the U.S. at the time of the interim analysis. Patients were randomized 2:1 to cabozantinib or placebo in two separate cohorts (pNET, n=93; epNET, n=197). The epNET cohort included patients with the following primary tumor sites: gastrointestinal (GI) tract, lung and other. Each cohort was randomized separately and had its own statistical analysis plan. Patients must have had measurable disease per RECIST 1.1 criteria and must have experienced disease progression or intolerance after at least one U.S. FDA-approved line of prior therapy other than somatostatin analogs. The primary endpoint in each cohort was PFS per RECIST 1.1 by retrospective blinded independent central review. Upon disease progression, patients were unblinded, and those receiving placebo were permitted to cross over to open-label therapy with cabozantinib. Secondary endpoints included overall survival, radiographic response rate and safety. More information about this trial is available at ClinicalTrials.gov.

About Neuroendocrine Tumors (NET)
Neuroendocrine tumors (NET) are cancers that begin in the specialized cells of the body’s neuroendocrine system.1 These cells have traits of both hormone-producing endocrine cells and nerve cells.1 In the U.S., it is estimated that 161,000 to 192,000 people are living with unresectable, locally advanced or metastatic NET.2 The number of people diagnosed with NET has been increasing in recent decades.3 Functional NET release peptide hormones that can cause debilitating symptoms, like diarrhea, hypertension and flushing, which may require focused treatment, while symptoms of non-functional NET are related primarily to tumor growth.4,5 Most NET take years to develop and grow slowly, but eventually, all patients with advanced or metastatic NET will develop refractory and progressing disease.6,7

NET can develop in any part of the body but most commonly start in the gastrointestinal (GI) tract or in the lungs, where they have historically been referred to as carcinoid tumors and are more recently called epNET.1 The five-year survival rates for advanced GI and lung NET are 68% and 55%, respectively.8,9 NET can also start in the pancreas, where they tend to be more aggressive, with a five-year survival rate of only 23% for advanced disease.1,10 For advanced NET patients, treatment options include somatostatin analogs, chemotherapy, targeted therapy and peptide-receptor radionuclide therapy.11

About CABOMETYX (cabozantinib)
In the U.S., CABOMETYX tablets are approved as monotherapy for the treatment of patients with advanced renal cell carcinoma (RCC) and in combination with nivolumab as a first-line treatment for patients with advanced RCC; for the treatment of patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib; and for adult and pediatric patients 12 years of age and older with locally advanced or metastatic differentiated thyroid cancer (DTC) that has progressed following prior VEGFR-targeted therapy and who are radioactive iodine-refractory or ineligible. CABOMETYX tablets have also received regulatory approvals in the European Union and additional countries and regions worldwide. In 2016, Exelixis granted Ipsen Pharma SAS exclusive rights for the commercialization and further clinical development of cabozantinib outside of the U.S. and Japan. In 2017, Exelixis granted exclusive rights to Takeda Pharmaceutical Company Limited for the commercialization and further clinical development of cabozantinib for all future indications in Japan. Exelixis holds the exclusive rights to develop and commercialize cabozantinib in the U.S.

CABOMETYX is not indicated as a treatment for NET.

IMPORTANT SAFETY INFORMATION
WARNINGS AND PRECAUTIONS

Hemorrhage: Severe and fatal hemorrhages occurred with CABOMETYX. The incidence of Grade 3 to 5 hemorrhagic events was 5% in CABOMETYX patients in RCC, HCC, and DTC studies. Discontinue CABOMETYX for Grade 3 or 4 hemorrhage and prior to surgery as recommended. Do not administer CABOMETYX to patients who have a recent history of hemorrhage, including hemoptysis, hematemesis, or melena.

Perforations and Fistulas: Fistulas, including fatal cases, occurred in 1% of CABOMETYX patients. Gastrointestinal (GI) perforations, including fatal cases, occurred in 1% of CABOMETYX patients. Monitor patients for signs and symptoms of fistulas and perforations, including abscess and sepsis. Discontinue CABOMETYX in patients who experience a Grade 4 fistula or a GI perforation.

Thrombotic Events: CABOMETYX increased the risk of thrombotic events. Venous thromboembolism occurred in 7% (including 4% pulmonary embolism) and arterial thromboembolism in 2% of CABOMETYX patients. Fatal thrombotic events occurred in CABOMETYX patients. Discontinue CABOMETYX in patients who develop an acute myocardial infarction or serious arterial or venous thromboembolic events that require medical intervention.

Hypertension and Hypertensive Crisis: CABOMETYX can cause hypertension, including hypertensive crisis. Hypertension was reported in 37% (16% Grade 3 and <1% Grade 4) of CABOMETYX patients. Do not initiate CABOMETYX in patients with uncontrolled hypertension. Monitor blood pressure regularly during CABOMETYX treatment. Withhold CABOMETYX for hypertension that is not adequately controlled with medical management; when controlled, resume at a reduced dose. Permanently discontinue CABOMETYX for severe hypertension that cannot be controlled with anti-hypertensive therapy or for hypertensive crisis.

Diarrhea: Diarrhea occurred in 62% of CABOMETYX patients. Grade 3 diarrhea occurred in 10% of CABOMETYX patients. Monitor and manage patients using antidiarrheals as indicated. Withhold CABOMETYX until improvement to ≤ Grade 1, resume at a reduced dose.

Palmar-Plantar Erythrodysesthesia (PPE): PPE occurred in 45% of CABOMETYX patients. Grade 3 PPE occurred in 13% of CABOMETYX patients. Withhold CABOMETYX until improvement to Grade 1 and resume at a reduced dose for intolerable Grade 2 PPE or Grade 3 PPE.

Hepatotoxicity: CABOMETYX in combination with nivolumab can cause hepatic toxicity with higher frequencies of Grades 3 and 4 ALT and AST elevations compared to CABOMETYX alone.

Monitor liver enzymes before initiation of and periodically throughout treatment. Consider more frequent monitoring of liver enzymes than when the drugs are administered as single agents. For elevated liver enzymes, interrupt CABOMETYX and nivolumab and consider administering corticosteroids.

With the combination of CABOMETYX and nivolumab, Grades 3 and 4 increased ALT or AST were seen in 11% of patients. ALT or AST >3 times ULN (Grade ≥2) was reported in 83 patients, of whom 23 (28%) received systemic corticosteroids; ALT or AST resolved to Grades 0-1 in 74 (89%). Among the 44 patients with Grade ≥2 increased ALT or AST who were rechallenged with either CABOMETYX (n=9) or nivolumab (n=11) as a single agent or with both (n=24), recurrence of Grade ≥2 increased ALT or AST was observed in 2 patients receiving CABOMETYX, 2 patients receiving nivolumab, and 7 patients receiving both CABOMETYX and nivolumab. Withhold and resume at a reduced dose based on severity.

Adrenal Insufficiency: CABOMETYX in combination with nivolumab can cause primary or secondary adrenal insufficiency. For Grade 2 or higher adrenal insufficiency, initiate symptomatic treatment, including hormone replacement as clinically indicated. Withhold CABOMETYX and/or nivolumab and resume CABOMETYX at a reduced dose depending on severity.

Adrenal insufficiency occurred in 4.7% (15/320) of patients with RCC who received CABOMETYX with nivolumab, including Grade 3 (2.2%), and Grade 2 (1.9%) adverse reactions. Adrenal insufficiency led to permanent discontinuation of CABOMETYX and nivolumab in 0.9% and withholding of CABOMETYX and nivolumab in 2.8% of patients with RCC.

Approximately 80% (12/15) of patients with adrenal insufficiency received hormone replacement therapy, including systemic corticosteroids. Adrenal insufficiency resolved in 27% (n=4) of the 15 patients. Of the 9 patients in whom CABOMETYX with nivolumab was withheld for adrenal insufficiency, 6 reinstated treatment after symptom improvement; of these, all (n=6) received hormone replacement therapy and 2 had recurrence of adrenal insufficiency.

Proteinuria: Proteinuria was observed in 8% of CABOMETYX patients. Monitor urine protein regularly during CABOMETYX treatment. For Grade 2 or 3 proteinuria, withhold CABOMETYX until improvement to ≤ Grade 1 proteinuria; resume CABOMETYX at a reduced dose. Discontinue CABOMETYX in patients who develop nephrotic syndrome.

Osteonecrosis of the Jaw (ONJ): ONJ occurred in <1% of CABOMETYX patients. ONJ can manifest as jaw pain, osteomyelitis, osteitis, bone erosion, tooth or periodontal infection, toothache, gingival ulceration or erosion, persistent jaw pain, or slow healing of the mouth or jaw after dental surgery. Perform an oral examination prior to CABOMETYX initiation and periodically during treatment. Advise patients regarding good oral hygiene practices. Withhold CABOMETYX for at least 3 weeks prior to scheduled dental surgery or invasive dental procedures, if possible. Withhold CABOMETYX for development of ONJ until complete resolution, resume at a reduced dose.

Impaired Wound Healing: Wound complications occurred with CABOMETYX. Withhold CABOMETYX for at least 3 weeks prior to elective surgery. Do not administer CABOMETYX for at least 2 weeks after major surgery and until adequate wound healing. The safety of resumption of CABOMETYX after resolution of wound healing complications has not been established.

Reversible Posterior Leukoencephalopathy Syndrome (RPLS): RPLS, a syndrome of subcortical vasogenic edema diagnosed by characteristic findings on MRI, can occur with CABOMETYX. Evaluate for RPLS in patients presenting with seizures, headache, visual disturbances, confusion, or altered mental function. Discontinue CABOMETYX in patients who develop RPLS.

Thyroid Dysfunction: Thyroid dysfunction, primarily hypothyroidism, has been observed with CABOMETYX. Based on the safety population, thyroid dysfunction occurred in 19% of patients treated with CABOMETYX, including Grade 3 in 0.4% of patients.

Patients should be assessed for signs of thyroid dysfunction prior to the initiation of CABOMETYX and monitored for signs and symptoms of thyroid dysfunction during CABOMETYX treatment. Thyroid function testing and management of dysfunction should be performed as clinically indicated.

Hypocalcemia: CABOMETYX can cause hypocalcemia. Based on the safety population, hypocalcemia occurred in 13% of patients treated with CABOMETYX, including Grade 3 in 2% and Grade 4 in 1% of patients. Laboratory abnormality data were not collected in CABOSUN.

In COSMIC-311, hypocalcemia occurred in 36% of patients treated with CABOMETYX, including Grade 3 in 6% and Grade 4 in 3% of patients.

Monitor blood calcium levels and replace calcium as necessary during treatment. Withhold and resume at reduced dose upon recovery or permanently discontinue CABOMETYX depending on severity.

Embryo-Fetal Toxicity: CABOMETYX can cause fetal harm. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Verify the pregnancy status of females of reproductive potential prior to initiating CABOMETYX and advise them to use effective contraception during treatment and for 4 months after the last dose.

ADVERSE REACTIONS
The most common (≥20%) adverse reactions are:

CABOMETYX as a single agent: diarrhea, fatigue, PPE, decreased appetite, hypertension, nausea, vomiting, weight decreased, and constipation.

CABOMETYX in combination with nivolumab: diarrhea, fatigue, hepatotoxicity, PPE, stomatitis, rash, hypertension, hypothyroidism, musculoskeletal pain, decreased appetite, nausea, dysgeusia, abdominal pain, cough, and upper respiratory tract infection.

DRUG INTERACTIONS

Strong CYP3A4 Inhibitors: If coadministration with strong CYP3A4 inhibitors cannot be avoided, reduce the CABOMETYX dosage. Avoid grapefruit or grapefruit juice.

Strong CYP3A4 Inducers: If coadministration with strong CYP3A4 inducers cannot be avoided, increase the CABOMETYX dosage. Avoid St. John’s wort.

USE IN SPECIFIC POPULATIONS

Lactation: Advise women not to breastfeed during CABOMETYX treatment and for 4 months after the final dose.

Hepatic Impairment: In patients with moderate hepatic impairment, reduce the CABOMETYX dosage. Avoid CABOMETYX in patients with severe hepatic impairment.

Please see accompanying full Prescribing Information
View Source

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.FDA.gov/medwatch or call 1-800-FDA-1088.

On August 6, 2024 Exelixis, Inc. (Nasdaq: EXEL) reported financial results for the second quarter of 2024, provided an update on progress toward achieving key corporate objectives, and detailed its recent and anticipated commercial, clinical and pipeline development milestones (Press release, Exelixis, AUG 6, 2024, View Source [SID1234645417]).

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"Exelixis is well positioned for an impactful second half of 2024 as we continue to grow the cabozantinib franchise, execute on our regulatory and development objectives, and advance our next-generation pipeline," said Michael M. Morrissey, Ph.D., President and CEO, Exelixis. "Cabozantinib’s second quarter commercial performance was strong both in the U.S. and globally, with Ipsen’s success prompting a $150 million milestone payment to Exelixis based on sales over the past four quarters. On the regulatory front, the FDA accepted the sNDA for cabozantinib in advanced NET, granted standard review and assigned a target action date of April 3, 2025. We’re actively preparing for launch and excited at the prospect of bringing this new treatment option to previously treated advanced NET patients with high unmet medical need. At the same time, we are prioritizing our clinical pipeline with plans to initiate a new phase 3 pivotal trial for zanzalintinib in NET, advance phase 1 efforts for XL309 and XB010, and discontinue development of XB002. I’d like to thank the entire Exelixis team for their hard work and contributions toward achieving these important milestones for cabozantinib and advancing our broad, differentiated pipeline of oncology therapeutics to help the patients we serve."

Second Quarter 2024 Financial Results

Total revenues for the quarter ended June 30, 2024 were $637.2 million, as compared to $469.8 million for the comparable period in 2023.

Total revenues for the quarter ended June 30, 2024 included net product revenues of $437.6 million, as compared to $409.6 million for the comparable period in 2023. The increase in net product revenues was primarily due to an increase in sales volume and average net selling price.

Collaboration revenues, composed of license revenues and collaboration services revenues, were $199.6 million for the quarter ended June 30, 2024, as compared to $60.2 million for the comparable period in 2023. The increase in collaboration revenues was primarily related to an increase in milestone-related revenues recognized in the quarter and higher royalty revenues for the sales of cabozantinib outside of the U.S. generated by Exelixis’ collaboration partners, Ipsen Pharma SAS (Ipsen) and Takeda Pharmaceutical Company Limited, partially offset by a decrease in development cost reimbursements earned.

Research and development expenses for the quarter ended June 30, 2024 were $211.1 million, as compared to $232.6 million for the comparable period in 2023. The decrease in research and development expenses was primarily related to decreases in license and other collaboration costs and clinical trial costs, partially offset by an increase in manufacturing costs to support our development candidates.

Selling, general and administrative expenses for the quarter ended June 30, 2024 were $132.0 million, as compared to $141.7 million for the comparable period in 2023. The decrease in selling, general and administrative expenses was primarily related to a decrease in legal and advisory fees related to the proxy contest in the prior year.

Provision for income taxes for the quarter ended June 30, 2024 was $66.7 million, as compared to $19.2 million for the comparable period in 2023.

GAAP net income for the quarter ended June 30, 2024 was $226.1 million, or $0.78 per share, basic and $0.77 per share, diluted, as compared to GAAP net income of $81.2 million, or $0.25 per share, basic and diluted, for the comparable period in 2023. GAAP net income per share for the quarter ended June 30, 2024 was favorably impacted by lower weighted-average common shares outstanding for the quarter ended June 30, 2024, as compared to the comparable period in 2023, as a result of the stock repurchase programs.

Non-GAAP net income for the quarter ended June 30, 2024 was $245.6 million, or $0.85 per share, basic and $0.84 per share, diluted, as compared to non-GAAP net income of $100.3 million, or $0.31 per share, basic and diluted, for the comparable period in 2023.

Non-GAAP Financial Measures

To supplement Exelixis’ financial results presented in accordance with U.S. Generally Accepted Accounting Principles (GAAP), Exelixis presents non-GAAP net income (and the related per share measures), which excludes from GAAP net income (and the related per share measures) stock-based compensation expense, adjusted for the related income tax effect for all periods presented.

Exelixis believes that the presentation of these non-GAAP financial measures provides useful supplementary information to, and facilitates additional analysis by, investors. In particular, Exelixis believes that these non-GAAP financial measures, when considered together with its financial information prepared in accordance with GAAP, can enhance investors’ and analysts’ ability to meaningfully compare Exelixis’ results from period to period, and to identify operating trends in Exelixis’ business. Exelixis has excluded stock-based compensation expense, adjusted for the related income tax effect, because it is a non-cash item that may vary significantly from period to period as a result of changes not directly or immediately related to the operational performance for the periods presented. Exelixis also regularly uses these non-GAAP financial measures internally to understand, manage and evaluate its business and to make operating decisions.

These non-GAAP financial measures are in addition to, not a substitute for, or superior to, measures of financial performance prepared in accordance with GAAP. Exelixis encourages investors to carefully consider its results under GAAP, as well as its supplemental non-GAAP financial information and the reconciliation between these presentations, to more fully understand Exelixis’ business. Reconciliations between GAAP and non-GAAP results are presented in the tables of this release.

2024 Financial Guidance

Exelixis is providing the following updated financial guidance for fiscal year 2024 (1):

Total revenues

$1.975 billion – $2.075 billion

Net product revenues (2)

$1.650 billion – $1.750 billion

Cost of goods sold

4% – 5% of net product revenues

Research and development expenses (3)

$925 million – $975 million

Selling, general and administrative expenses (4)

$450 million – $500 million

Effective tax rate

20% – 22%

____________________

(1) 2024 financial guidance excludes expenses related to the restructuring plan announced in January 2024.

(2) Exelixis’ 2024 net product revenues guidance range includes the impact of a U.S. wholesale acquisition cost increase of 2.2% for both CABOMETYX and COMETRIQ effective on January 1, 2024.

(3) Includes $40 million of non-cash stock-based compensation expense.

(4) Includes $60 million of non-cash stock-based compensation expense.

Cabozantinib and Pipeline Highlights

Cabozantinib Franchise Net Product Revenues and Royalties. Net product revenues generated by the cabozantinib franchise in the U.S. were $437.6 million during the second quarter of 2024, with net product revenues of $433.3 million from CABOMETYX (cabozantinib) and $4.2 million from COMETRIQ (cabozantinib). Based upon cabozantinib-related net product revenues generated by Exelixis’ collaboration partners during the quarter ended June 30, 2024, Exelixis earned $41.2 million in royalty revenues.

Achievement of Cabozantinib Sales-Based Milestone from Ipsen. Today, Exelixis announced it earned and recognized in license revenues a $150 million commercial milestone from Ipsen during the second quarter of 2024 based on Ipsen achieving $600 million in cumulative net sales of cabozantinib in its related license territory over four consecutive quarters. Exelixis expects to receive the milestone payment during the third quarter of 2024.

FDA Accepts for Standard Review the sNDA for Cabozantinib for Patients with Advanced NET; Updated Results from Phase 3 CABINET Study to be Presented during an Oral Presentation at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2024. Today, Exelixis announced that the FDA accepted its sNDA for cabozantinib for patients with previously treated advanced pancreatic NET (pNET), and for patients with previously treated advanced extra-pancreatic NET (epNET). The FDA assigned a standard review with a Prescription Drug User Fee Act (PDUFA) target action date of April 3, 2025. The FDA also granted orphan drug designation to cabozantinib for the treatment of pNET. The application was based on results from the phase 3 CABINET trial, which evaluated cabozantinib compared with placebo in patients with previously treated pNET and epNET. The CABINET study is sponsored by the National Cancer Institute (NCI), part of the National Institutes of Health, and led by the NCI-funded Alliance for Clinical Trials in Oncology. Updated results from CABINET, including final results on the primary efficacy endpoint of progression-free survival by Blinded Independent Central Review, will be presented during the ESMO (Free ESMO Whitepaper) Congress 2024 in September.

Exelixis Partner Ipsen Opts into Phase 3 CABINET Pivotal Trial in Advanced NET. In July, Ipsen announced it opted into the phase 3 CABINET pivotal trial, expanding the existing collaboration and license agreement with Exelixis and permitting Ipsen to seek potential marketing authorizations for CABOMETYX in advanced pNET and epNET from regulatory authorities outside of the U.S. and Japan. As part of the agreement, Exelixis is eligible to receive a reimbursement of a portion of costs related to the trial, as well as milestone payments for potential future regulatory action by the European Medicines Agency. The decision to expand the existing agreement was based on detailed results from the CABINET trial, which were first presented at the ESMO (Free ESMO Whitepaper) Congress 2023.

Phase 3 CONTACT-02 Metastatic Castration-Resistant Prostate Cancer (mCRPC) Study Update and Intention to Submit sNDA in 2024. Today, Exelixis announced that the final overall survival (OS) analysis for the phase 3 CONTACT-02 trial has been completed. This study is evaluating cabozantinib in combination with atezolizumab compared with a second novel hormonal therapy (NHT) in patients with mCRPC and measurable soft-tissue disease who have progressed after treatment with one prior NHT. As previously reported, the CONTACT-02 study met one of its two primary endpoints, demonstrating a statistically significant benefit in progression-free survival (PFS) (hazard ratio: 0.65; 95% confidence interval: 0.50–0.84; p=0.0007) in the predefined PFS intent-to-treat population (i.e., the first 400 randomized patients). While final OS continued to favor the combination of cabozantinib and atezolizumab, it did not achieve statistical significance. The safety profile of the combination regimen was reflective of the known safety profiles for each single agent and was consistent with the known tolerability profile of approved immune checkpoint inhibitor-tyrosine kinase inhibitor combinations in advanced solid tumors. Exelixis intends to submit an sNDA to the FDA this year and to present these final data at a future medical meeting.

Enrollment Completion for Zanzalintinib Phase 3 STELLAR-303 Study and Announcement of New Pivotal Trial for Zanzalintinib in Neuroendocrine Tumors. Today, Exelixis announced that enrollment has been completed in the STELLAR-303 phase 3 pivotal study. STELLAR-303 is evaluating zanzalintinib in combination with atezolizumab compared with regorafenib in patients with metastatic refractory colorectal cancer that is not microsatellite instability-high or mismatch repair-deficient. The primary endpoint in the study is OS in the patients without liver metastases. Exelixis anticipates preliminary results from the study to readout in 2025. Additionally, Exelixis intends to initiate a new phase 3 pivotal trial, STELLAR-311, evaluating zanzalintinib compared with everolimus as a first oral therapy in patients with pNET and epNET, in the first half of 2025.

Initiation of Phase 1 Clinical Trial Evaluating XB010 in Patients with Advanced Solid Tumors. Today, Exelixis announced the initiation of the dose-escalation stage of the first-in-human phase 1 clinical trial of XB010 in patients with locally advanced or metastatic solid tumors. XB010, an antibody-drug conjugate (ADC) consisting of a monomethyl auristatin E payload conjugated to a monoclonal antibody targeting the tumor antigen 5T4, is the first custom ADC generated through Exelixis’ biotherapeutics collaboration network. The dose-escalation stage of this phase 1, global, open-label study will evaluate XB010 as a single agent and in combination with pembrolizumab to inform the cohort-expansion stage. The expansion cohorts are designed to further assess the tolerability and activity of monotherapy and of the combination in specific indications.

Portfolio Prioritization Update. Today, Exelixis announced it will discontinue the development of XB002, the company’s tissue factor (TF)-targeting ADC, as part of its portfolio prioritization efforts. Based on available data, the compound is unlikely to improve upon tisotumab vedotin or other competitor TF-targeting ADCs currently in development. The company plans to disclose data from the phase 1 JEWEL-101 study, evaluating XB002 in advanced solid tumors, at a later date. Preclinical development of XB371, its ADC consisting of a topoisomerase payload conjugated to a TF-targeting monoclonal antibody, is ongoing. Exelixis plans to reallocate resources to new pivotal trials with zanzalintinib, advancing XL309 and its growing pipeline.

Corporate Highlights

Settlement of CABOMETYX Patent Litigation with Cipla Limited and Cipla USA. In May, Exelixis entered into a Settlement and License Agreement (Agreement) with Cipla Ltd. and Cipla USA, Inc. (individually and collectively referred to as Cipla) resolving two patent litigations brought by Exelixis in response to Cipla’s Abbreviated New Drug Application (ANDA) seeking approval to market generic versions of CABOMETYX tablets (20 mg / 40 mg / 60 mg) prior to the expiration of the applicable patents. Pursuant to the terms of the Agreement, Exelixis will grant Cipla a license to market generic versions of CABOMETYX in the United States beginning on January 1, 2031, if approved by the FDA and subject to conditions and exceptions common to agreements of this type. The U.S. District Court for the District of Delaware dismissed the case without prejudice in July 2024 per the parties’ joint request, effectively terminating all ongoing Hatch-Waxman litigation between Exelixis and Cipla regarding CABOMETYX patents

Completion of the $450 million 2024 Stock Repurchase Program. As of June 30, 2024, Exelixis completed the repurchase of 20.3 million shares of the company’s common stock for a total of $450 million, fulfilling its commitment under the stock repurchase program announced in January 2024. With the completion of this 2024 stock repurchase program, the company has returned $1 billion to shareholders since the initial $550 million stock repurchase program was authorized in March 2023.

Announcement of Additional Stock Repurchase Program for up to $500 million through the End of 2025. Today, Exelixis announced that the company’s Board of Directors has authorized the repurchase of up to an additional $500 million of the company’s common stock through the end of 2025. The newly authorized stock repurchase program is the third such program undertaken by Exelixis since March 2023. Stock repurchases under the newly authorized program may be made from time to time through a variety of methods, which may include open market purchases, in block trades, accelerated share repurchase transactions, exchange transactions, or any combination of such methods. The timing and amount of any stock repurchases under the stock repurchase program will be based on a variety of factors, including ongoing assessments of the capital needs of the business, alternative investment opportunities, the market price of Exelixis’ common stock and general market conditions.

Basis of Presentation

Exelixis has adopted a 52- or 53-week fiscal year that generally ends on the Friday closest to December 31. For convenience, references in this press release as of and for the fiscal periods ended June 28, 2024 are indicated as being as of and for the periods ended June 30, 2024.

Conference Call and Webcast

Exelixis management will discuss the company’s financial results for the second quarter of 2024 and provide a general business update during a conference call beginning at 5:00 p.m. ET / 2:00 p.m. PT today, Tuesday, August 6, 2024.

To access the conference call, please register using this link. Upon registration, a dial-in number and unique PIN will be provided to join the call. To access the live webcast link, log onto www.exelixis.com and proceed to the Event Calendar page under the Investors & News heading. A webcast replay of the conference call will also be archived on www.exelixis.com for one year.

On August 6, 2024 Elevation Oncology, Inc. (Nasdaq: ELEV), an innovative oncology company focused on the discovery and development of selective cancer therapies to treat patients across a range of solid tumors with significant unmet medical needs, reported financial results for the second quarter ended June 30, 2024, and highlighted recent business achievements (Press release, Elevation Oncology, AUG 6, 2024, View Source;utm_medium=rss&utm_campaign=elevation-oncology-reports-second-quarter-2024-financial-results-and-highlights-recent-business-achievements [SID1234645416]).

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"Today, we announced promising initial data from our Phase 1 trial evaluating monotherapy EO-3021, which reinforce clinical proof-of-concept and support EO-3021’s potential as a best-in-class Claudin 18.2 antibody drug conjugate. We are particularly excited to see encouraging anti-tumor activity in patients with Claudin 18.2-expressing gastric or GEJ cancer, as well as a differentiated safety profile, demonstrating the value of a targeted therapeutic approach and the benefit of EO-3021’s site-specific conjugation," said Joseph Ferra, President and Chief Executive Officer of Elevation Oncology. "These results support our broad clinical development program for EO-3021 and strengthen our conviction that EO-3021 can provide meaningful benefit to patients living with gastric or GEJ cancer."

Mr. Ferra continued, "Looking ahead, we remain on track to advance into monotherapy dose expansion and initiate the combination portion of our Phase 1 trial evaluating EO-3021 by year-end, report additional monotherapy data for EO-3021 in the first half of 2025, and nominate a development candidate from our HER3-ADC program in the second half of 2024. This year has been transformative for Elevation Oncology, marked by strong execution toward our goal of bringing important treatment options to patients with significant unmet medical needs, and we are eager to continue these efforts as we advance our pipeline of differentiated ADC therapies."

Recent Business Achievements

Earlier today, Elevation Oncology announced promising initial data from the dose escalation portion of the ongoing Phase 1 clinical trial of EO-3021 in patients with advanced, unresectable or metastatic solid tumors likely to express Claudin 18.2, including gastric, gastroesophageal junction (GEJ), pancreatic or esophageal cancers. As of the data cutoff date of June 10, 2024:
EO-3021 was observed to be generally well-tolerated. No neutropenia or peripheral neuropathy/hypoesthesia, both known toxicities associated with monomethyl auristatin E (MMAE), were observed in the safety population of 32 patients treated with EO-3021.
In seven patients with Claudin 18.2 in ≥20% of tumor cells at IHC 2+/3+, the objective response rate (ORR) was 42.8% (three confirmed partial responses, one of which was confirmed following the June 10, 2024, data cutoff) and the disease control rate (DCR) was 71.4%, including two patients with stable disease (SD).
In eight patients with Claudin 18.2 in <20% of tumor cells at IHC 2+/3+, the ORR was 0% and the DCR was 50%, including four patients with SD.
A press release with further details regarding these results is available in the News Releases section of Elevation Oncology’s investor relations website at View Source
In June 2024, Elevation Oncology announced plans to expand its ongoing Phase 1 clinical trial of EO-3021 to include two combination cohorts evaluating EO-3021 for the treatment of advanced gastric or GEJ cancer. Pursuant to clinical supply agreements with Lilly and Company and GSK, respectively, Elevation Oncology will evaluate EO-3021 in combination with ramucirumab, a VEGFR2 inhibitor, in the second-line setting and in combination with dostarlimab, a PD-1 inhibitor, in the front-line setting.
Expected Upcoming Milestones

EO-3021:

Initiate dosing in combination portion of the ongoing Phase 1 clinical trial of EO-3021 by year-end 2024.
Share additional data from the ongoing Phase 1 clinical trial of monotherapy EO-3021, including from the dose expansion cohort, in the first half of 2025.
HER3-ADC:

Nominate development candidate from HER3-ADC program in the second half of 2024.
Second Quarter 2024 Financial Results

As of June 30, 2024, Elevation Oncology had cash, cash equivalents and marketable securities totaling $110.8 million, compared to $83.1 million as of December 31, 2023. The increase in cash reflects net proceeds of $44.2 million, which Elevation Oncology raised through its at-the-market (ATM) facility in the first half of 2024, partially offset by cash used to fund operating activities.

Research and development (R&D) expenses for the second quarter of 2024 were $6.6 million, compared to $6.0 million for the second quarter of 2023. The increase in R&D expenses in the second quarter of 2024 was primarily due to increased EO-3021 clinical trial expenses.

General and administrative (G&A) expenses for the second quarter of 2024 were $4.4 million, compared to $3.8 million for the second quarter of 2023. The increase in G&A expenses in the second quarter of 2024 was primarily due to increased professional fees, including costs for accounting and legal services, and increased utilization of consultants.

Net loss for the second quarter of 2024 was $10.5 million, compared to $10.1 million for the second quarter of 2023.

Financial Outlook

Elevation Oncology expects its existing cash, cash equivalents and marketable securities as of June 30, 2024 to be sufficient to fund its current operations into 2026.

Conference Call Information

Elevation Oncology will host a live conference call and webcast at 8:30 a.m. ET today to discuss the initial EO-3021 safety and efficacy data announced today. Participants may register for the conference call here. It is recommended that participants join the call ten minutes prior to the scheduled start.

A webcast of the call will also be available on the Events page of Elevation Oncology’s investor relations website at View Source The archived webcast will be available on the website approximately two hours after the conference call and will be available for 90 days following the call.

About EO-3021

EO-3021 (also known as SYSA1801) is a differentiated, clinical-stage antibody drug conjugate (ADC) with best-in-class potential comprised of an immunoglobulin G1 (IgG1) monoclonal antibody (mAb) that targets Claudin 18.2. EO-3021 is site-specifically conjugated to the monomethyl auristatin E (MMAE) payload via a cleavable linker with a drug-to-antibody ratio (DAR) of 2. Claudin 18.2 is a specific isoform of Claudin 18 that is normally expressed in gastric epithelial cells. During malignant transformation, the tight junctions may become disrupted, exposing Claudin 18.2 and allowing them to be accessible by Claudin 18.2 targeting agents. Elevation Oncology is evaluating EO-3021 in a Phase 1 study (NCT05980416) in patients with advanced, unresectable or metastatic solid tumors likely to express Claudin 18.2 including gastric, gastroesophageal junction, pancreatic or esophageal cancers.

Elevation Oncology has the exclusive rights to develop and commercialize EO-3021 in all global territories outside Greater China.

On August 6, 2024 Elevation Oncology, Inc. (Nasdaq: ELEV), an innovative oncology company focused on the discovery and development of selective cancer therapies to treat patients across a range of solid tumors with significant unmet medical needs, reported promising initial data from the dose escalation portion of the ongoing Phase 1 clinical trial of EO-3021 in patients with advanced, unresectable or metastatic solid tumors likely to express Claudin 18.2, including gastric, gastroesophageal junction (GEJ), pancreatic or esophageal cancers (Press release, Elevation Oncology, AUG 6, 2024, View Source;utm_medium=rss&utm_campaign=elevation-oncology-announces-promising-initial-data-from-phase-1-clinical-trial-evaluating-eo-3021-in-patients-with-advanced-unresectable-or-metastatic-solid-tumors-likely-to-express-claudin-18-2 [SID1234645415]).

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Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

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"Gastric and GEJ cancers are devastating diseases, which occur frequently in the U.S. and globally and which, despite recent advancements, still have high levels of mortality," said Kohei Shitara, M.D., Chief, Department of Gastrointestinal Oncology, National Cancer Center Hospital East in Kashiwa, Japan and principal investigator on the Phase 1 clinical trial. "There is a particular need for highly selective therapies that benefit patients with Claudin 18.2-expressing tumors. To that end, I am excited by the initial data with EO-3021, which suggest it could change the treatment paradigm for a significant portion of patients with gastric or GEJ cancer. I am excited to evaluate EO-3021 in the expansion portion of this Phase 1 clinical trial."

"We are pleased to share initial data from our Phase 1 clinical trial of EO-3021," said Valerie Malyvanh Jansen, M.D., Ph.D., Chief Medical Officer of Elevation Oncology. "EO-3021 was designed to maximize efficacy while minimizing the potential for free MMAE, with the goal of offering patients an improved safety profile and physicians a more readily combinable agent. We are encouraged to see the benefits of EO-3021’s site-specific conjugation translate clinically, with minimal MMAE-associated toxicities observed in our Phase 1 trial. Coupled with the promising anti-tumor activity reported in patients with gastric or GEJ cancer, the data suggest that EO-3021 is a potential best-in-class Claudin 18.2 antibody drug conjugate. We look forward to advancing into monotherapy dose expansion and initiating our combination cohorts in the months ahead, as well as reporting additional data from our ongoing trial in the first half of 2025."

Data from the Ongoing Phase 1 Clinical Trial

EO-3021 was evaluated in the dose escalation stage of a Phase 1 clinical trial in patients with advanced, unresectable or metastatic solid tumors likely to express Claudin 18.2, including gastric, GEJ, pancreatic or esophageal cancers. As of the data cutoff date of June 10, 2024, 32 patients had been treated in the dose escalation portion of the Phase 1 clinical trial at four dose levels (ranging from 1.0 mg/kg to 2.9 mg/kg once every three weeks (Q3W), including 26 patients with gastric or GEJ cancer. The median age was 65 years (ranging from 45 to 83) and the median number of prior lines of therapy was three (ranging from one to seven).

Initial Safety Data

As of the data cutoff of June 10, 2024, EO-3021 was observed to be generally well-tolerated. No Grade 4 or 5 treatment-related adverse events were reported, and less than 10% of patients discontinued EO-3021 due to adverse events. Importantly, no neutropenia or peripheral neuropathy/hypoesthesia, both known toxicities associated with monomethyl auristatin E (MMAE), were observed in the safety population of 32 patients treated with EO-3021.

Across all grades, the most common treatment-emergent adverse events (reported in ≥20% of patients) were nausea (56%), decreased appetite (47%), fatigue (41%) and diarrhea (28%). Four dose-limiting toxicities (one each of Grade 3 fatigue, encephalopathy, worsening decreased appetite, and Grade 2 decreased appetite requiring a dose reduction at Cycle 2) were observed at the 2.9 mg/kg dose level, leading to the decision to select the 2.0 mg/kg and 2.5 mg/kg Q3W doses for evaluation in the dose expansion portion of the Phase 1 trial.

Initial Efficacy Data in Gastric and GEJ Cancer

As of the data cutoff date of June 10, 2024, 15 patients with gastric or GEJ cancers were evaluable for efficacy with measurable disease, at least one post-baseline scan, and available Claudin 18.2 IHC results. Seven of these 15 patients (47%) had tumors with Claudin 18.2 expression in ≥20% of tumor cells at IHC 2+/3+. Claudin 18.2 expression was determined retrospectively using a Claudin 18.2-specific IHC assay.

In seven patients with Claudin 18.2 in ≥20% of tumor cells at IHC 2+/3+, the objective response rate (ORR) was 42.8% (three confirmed partial responses, one of which was confirmed following the June 10, 2024, data cutoff) and the disease control rate (DCR) was 71.4%, including two patients with stable disease (SD).
In eight patients with Claudin 18.2 in <20% of tumor cells at IHC 2+/3+, the ORR was 0% and the DCR was 50%, including four patients with SD.
Clinical Development Plans for EO-3021

Elevation Oncology plans to initiate enrollment in the dose expansion portion of the ongoing Phase 1 clinical trial, further exploring two doses of EO-3021: 2.0 mg/kg IV Q3W and 2.5 mg/kg IV Q3W. These doses were selected with the goal of further characterizing EO-3021 in order to select an optimized dose for further clinical development.

The primary objective of the study is to evaluate the safety, tolerability and preliminary anti-tumor activity of EO-3021 in patients with gastric or GEJ cancer, who have progressed on or after standard therapy or who are intolerable of available standard therapy. An exploratory objective of the study is to assess the association of Claudin 18.2 expression and objective response. Additionally, data from the dose escalation portion of Elevation Oncology’s Phase 1 trial suggest that a biomarker patient selection strategy will be an important component of future clinical development. Elevation Oncology is working to identify the appropriate biomarker threshold and plans to introduce a biomarker cutoff as part of the dose expansion portion of this Phase 1 trial. Elevation Oncology expects to share additional data from the Phase 1 trial, including from the dose expansion cohort, in the first half of 2025.

Additionally, Elevation Oncology plans to expand its ongoing Phase 1 clinical trial to include combination cohorts evaluating EO-3021 for the treatment of advanced or metastatic gastric or GEJ cancer in the first- and second-line setting. As previously disclosed, the combination cohorts will evaluate EO-3021 in combination with ramucirumab, a VEGFR2-inhibitor, in the second-line setting, and in combination with dostarlimab, a PD-1 inhibitor, in the first-line setting. Elevation Oncology expects to initiate dosing in the combination portion of the Phase 1 trial by year-end 2024.

Conference Call Information

Elevation Oncology will host a live conference call and webcast at 8:30 a.m. ET today to discuss the initial safety and efficacy data announced today. Participants may register for the conference call here. It is recommended that participants join the call ten minutes prior to the scheduled start.

A webcast of the call will also be available on the Events page of Elevation Oncology’s investor relations website at View Source The archived webcast will be available on the website approximately two hours after the conference call and will be available for 90 days following the call.

About EO-3021

EO-3021 (also known as SYSA1801) is a differentiated, clinical-stage antibody drug conjugate (ADC) with best-in-class potential comprised of an immunoglobulin G1 (IgG1) monoclonal antibody (mAb) that targets Claudin 18.2. EO-3021 is site-specifically conjugated to the monomethyl auristatin E (MMAE) payload via a cleavable linker with a drug-to-antibody ratio (DAR) of 2. Claudin 18.2 is a specific isoform of Claudin 18 that is normally expressed in gastric epithelial cells. During malignant transformation, the tight junctions may become disrupted, exposing Claudin 18.2 and allowing them to be accessible by Claudin 18.2 targeting agents. Elevation Oncology is evaluating EO-3021 in a Phase 1 study (NCT05980416) in patients with advanced, unresectable or metastatic solid tumors likely to express Claudin 18.2 including gastric, gastroesophageal junction, pancreatic or esophageal cancers.

Elevation Oncology has the exclusive rights to develop and commercialize EO-3021 in all global territories outside Greater China.

On August 6, 2024 Corvus Pharmaceuticals, Inc. (Corvus or the Company) (Nasdaq: CRVS), a clinical-stage biopharmaceutical company, reported a business update and announced financial results for the second quarter ended June 30, 2024 (Press release, Corvus Pharmaceuticals, AUG 6, 2024, View Source [SID1234645414]).

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"We have seen growing evidence supporting the central role of ITK in T cell biology and the significant potential of ITK inhibition as a new mechanism to treat a broad range of immune diseases and cancers," said Richard A. Miller, M.D., co-founder, president and chief executive officer of Corvus. "This includes early data from our Phase 1 clinical trial of soquelitinib in atopic dermatitis and our ongoing preclinical work exploring ITK inhibition in autoimmunity and inflammation. Based on this, we are increasingly optimistic that our ITK platform has the potential to improve clinical outcomes for a range of indications as an oral medication with an attractive tolerability profile. We have leveraged our experience in T cell lymphomas which has allowed us to gain a deeper understanding of the role of ITK in T cell biology that we can now apply to immune diseases. We remain on track to initiate a Phase 3 registrational trial in PTCL in the third quarter."

Business Update and Strategy

Prioritized Program: Soquelitinib (formerly CPI-818, Corvus’ selective ITK inhibitor)

Soquelitinib for Immune Diseases

Corvus continues to enroll patients at multiple clinical sites in its randomized, placebo-controlled Phase 1 clinical trial of soquelitinib in patients with moderate to severe atopic dermatitis. The trial is planned to enroll 64 patients that have failed at least one prior therapy across four different 28-day dosing regimens of soquelitinib compared to a placebo group. The endpoints include safety and improvement in Eczema Area and Severity Index. Patients and physicians will be blinded to treatment assignment.
Initial results, as of July 31, 2024, from three evaluable patients in the first cohort of the trial that completed the 28-day dosing regimen and follow-up visit demonstrated signs of clinical activity and corresponding changes in serum cytokine levels that are consistent with soquelitinib’s mechanism of action. These patients received a dose of 100 mg two-times a day, the lowest dose level planned for the study.
Corvus anticipates interim data from the Phase 1 clinical trial will be presented in the fourth quarter of 2024.
Recent published data from researchers at Cornell University demonstrated that ITK controls the fate of inflammatory Th17 cells. When ITK is inhibited by soquelitinib, the Th17 cells convert or switch to Treg cells that suppress inflammation. Soquelitinib treatment in an asthma model of mice with allergic airway inflammation significantly reduced the percentage of Th17 cells in the lung resulting in an increase in the ratio of Treg to Th17 cells. These studies confirm our understanding of the role of specific ITK inhibition in inflammation and are relevant to many immune diseases.
Corvus continues to advance its next-generation ITK inhibitor preclinical product candidates, which were designed to deliver precise T-cell modulation that is optimized for specific immunology indications. The next-generation ITK inhibitor candidates are part of the Company’s ongoing business development efforts to maximize the potential of the Company’s ITK inhibitor programs in immune diseases and cancers.

Soquelitinib for T Cell Lymphoma

Corvus continues to follow patients with relapsed T cell lymphoma in its Phase 1/1b clinical trial (no longer enrolling new patients) evaluating single agent therapy with soquelitinib. Updated interim data as of July 16, 2024:
A total of 25 patients were enrolled in the Phase 1/1b trial at the optimum 200 mg two-times a day dose and meet the eligibility criteria for the planned registrational Phase 3 clinical trial based on ≥1 and ≤3 prior therapies, including 23 evaluable patients.
For the 23 evaluable patients, objective responses (complete response, CR plus partial response, PR) were seen in nine patients (39%), including six CRs (26%) and three PRs. Compared to the prior data reported as of May 3, 2024, one patient with continued tumor regression achieved a CR that previously had a PR at the first follow up visit. See waterfall plot below.
Disease control (CR, PR and stable disease) was seen in 14 of 23 patients (61%). The stable disease group included five patients who achieved tumor reductions that did not meet the criteria for a PR.
Corvus anticipates initiating a registrational Phase 3 clinical trial of soquelitinib in patients with relapsed PTCL in the third quarter of 2024. There are currently no FDA fully approved agents for the treatment of relapsed PTCL and the FDA has granted Orphan Drug Designation for soquelitinib for the treatment of T cell lymphoma. Recently, the Company received a Pediatric Waiver from the FDA indicating that it would not be required to conduct clinical trials in a pediatric population for this indication.
As recently announced, soquelitinib has received Fast Track designation for treatment of adult patients with relapsed or refractory peripheral T cell lymphoma after at least 2 lines of systemic therapy.

Waterfall Plot for Patients in the 200 mg Dose Cohort of the Soquelitinib Phase 1/1b Clinical Trial for Peripheral T Cell Lymphoma. The plot shows the best percent change in tumor volume in the 23 evaluable patients (eligible patient population), as of July 16, 2024, that were measurable by CT scan or by Modified Severity-Weighted Assessment Tool (mSWAT) for patients with cutaneous involvement. PTCL-NOS, peripheral T cell lymphoma not otherwise specified; CTCL, cutaneous T cell lymphoma of either Sezary or mycosis fungoides type; NKTCL, natural killer cell T cell lymphoma; ALCL, anaplastic large cell lymphoma; AITL, angioimmunoblastic T cell lymphoma.

Collaboration with Kidney Cancer Research Consortium: Ciforadenant (adenosine A2a receptor inhibitor)

Corvus is collaborating with the Kidney Cancer Research Consortium in a Phase 1b/2 clinical trial evaluating ciforadenant as a potential first line therapy for metastatic renal cell cancer (RCC) in combination with ipilimumab (anti-CTLA-4) and nivolumab (anti-PD-1). The efficacy endpoint for the trial is deep response rate, defined as CR plus PRs of greater than 50% tumor volume reduction. The clinical trial is expected to enroll up to 60 patients and as of May 31, 2024 a total of 32 patients were enrolled in the trial. The protocol defined, interim pre-specified statistical threshold for efficacy is a 50% increase above the 32% deep response rate seen with previous ipilimumab/nivolumab combination trials in RCC conducted by investigators at the Kidney Cancer Research Consortium. As of May 31, 2024, the interim analysis of the clinical trial has met the threshold for efficacy and therefore enrollment continues.
In July 2024, a new U.S. patent was issued (United States Patent No. 12,023,337) by the U.S. Patent and Trademark Office that covers the use of ciforadenant for the treatment of cancer; foreign counterparts are pending.
Partner Led Program: Mupadolimab (anti-CD73)

Angel Pharmaceuticals, Corvus’ partner in China, is enrolling patients in an expansion cohort of a Phase 1/1b clinical trial of mupadolimab in patients with relapsed non-small cell lung cancer (NSCLC). In this clinical trial, patients will receive mupadolimab monotherapy.

Financial Results

As of June 30, 2024, Corvus had cash, cash equivalents and marketable securities of $47.2 million as compared to $27.1 million as of December 31, 2023. During the quarter ended June 30, 2024, the Company completed a registered direct offering in which it sold shares of common stock, pre-funded warrants and common warrants, generating $30.3 million in net proceeds.

Corvus expects full year 2024 net cash used in operating activities to be between approximately $24 million and $27 million, resulting in a projected cash balance of between approximately $31 million and $34 million at December 31, 2024. Based on its current plans, Corvus expects its cash to fund operations into the fourth quarter of 2025.

Research and development expenses for the three months ended June 30, 2024 totaled $4.1 million compared to $4.0 million for the same period in 2023. The increase of $0.1 million was primarily due to higher clinical trial costs associated with the development of soquelitinib.

The net loss for the three months ended June 30, 2024 was $4.3 million compared to a net loss of $6.5 million for the same period in 2023. Total stock compensation expense for the three months ended June 30, 2024 was $0.8 million compared to $0.5 for the same period in 2023 and the non-cash loss from Corvus’ equity method investment in Angel Pharmaceuticals was $0.6 million for the three months ended June 30, 2024 compared to a loss of $1.3 million for the same period in 2023. In addition, the Company recorded a non-cash gain of $1.8 million from the change in fair value of its warrant liability during the three months ended June 30, 2024 due to the warrants issued in the registered direct offering.

Conference Call Details
Corvus will host a conference call and webcast today, Tuesday, August 6, 2024, at 4:30 p.m. ET (1:30 p.m. PT), during which time management will provide a business update and discuss the second quarter 2024 financial results. The conference call can be accessed by dialing 1- 800-717-1738 (toll-free domestic) or 1- 646-307-1865 (international) or by clicking on this link for instant telephone access to the event. The live webcast may be accessed via the investor relations section of the Corvus website. A replay of the webcast will be available on Corvus’ website for 90 days.