On August 6, 2024 IDEAYA Biosciences, Inc. (Nasdaq: IDYA), a precision medicine oncology company committed to the discovery and development of targeted therapeutics, reported a business update, and announced financial results for the second quarter ended June 30, 2024 (Press release, Ideaya Biosciences, AUG 6, 2024, View Source [SID1234645421]).

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"We made significant progress advancing four potential first-in-class precision medicine oncology clinical programs this past quarter, and we are on-track to deliver our fifth potential first-in-class program to the clinic this year in Werner Helicase. Importantly, we presented preliminary clinical proof of concept data for IDE397 monotherapy in MTAP-deletion urothelial and lung cancer, demonstrating the ability to deliver confirmed RECIST responses with a favorable AE profile. The IDE397 combination therapy trials in MTAP-deletion solid tumors with our collaborators continue to progress, with the first patient dosed in the Phase 1 trial evaluating IDE397 with Gilead’s Trodelvy, and continued dose escalation in the AMG 193 clinical combination with Amgen. We look forward to hosting an investor R&D Day that will profile our rapidly advancing potential first-in-class precision medicine oncology pipeline, where we are targeting multiple additional development candidates by the end of this year," said Yujiro S. Hata, President and Chief Executive Officer, IDEAYA Biosciences.

"We were excited to share the compelling interim clinical data from the investigator- and company-sponsored Phase 2 trials of darovasertib in neoadjuvant UM, and look forward to discussing the registrational path forward with the FDA and providing our company-sponsored Phase 2 trial update in over 30 patients during the second half of this year. In addition, the most recent positive interim results observed with IDE397 monotherapy, in addition to the ongoing combination trials, bring us closer to potentially addressing a high unmet need in MTAP-deletion NSCLC, urothelial cancer and other solid tumors, and we are targeting developing a registrational plan in 2025. Separately, we anticipate initiating both the Phase 2 IDE161 monotherapy expansion cohort and the IDE161 in combination with KEYTRUDA cohort in the second half of 2024," said Darrin Beaupre, M.D., Ph.D., Chief Medical Officer, IDEAYA Biosciences.

Summary of Q2 and Recent Key Developments

Research and Clinical Development

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Darovasertib in neoadjuvant uveal melanoma (UM)
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Interim data from the investigator-sponsored Phase 2 trial were presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2024 meeting by Anthony Joshua, MBBS, PhD, FRACP, Head Department of Medical Oncology, Kinghorn Cancer Centre, St. Vincent’s Hospital in Sydney, and the lead principal investigator of the study.
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The company-sponsored Phase 2 trial has enrolled over 50 patients in 20 sites globally as of July 31, 2024; a clinical update from eight patients was provided. An additional clinical data update in over 30 patients is planned in the second half of 2024.
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IDEAYA has scheduled a Type C meeting with the U.S. Food and Drug Administration (FDA) to discuss a potential registrational trial for darovasertib in the neoadjuvant UM setting in the third quarter of 2024.
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IDE397 in MTAP-Deletion Solid Tumors
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Selected 30 mg as move-forward Phase 2 expansion dose in MTAP-deletion urothelial cancer and squamous non-small cell lung cancer (NSCLC). Reported positive interim data from 18 evaluable urothelial cancer and NSCLC patients.
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Announced first-patient-in (FPI) for Phase 1 trial evaluating IDE397 in combination with Gilead’s Trodelvy in MTAP-deletion urothelial cancer.
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The IDE397 / AMG 193 clinical combination dose escalation is ongoing. In the past quarter, IDEAYA, in consultation with Amgen, has now financially budgeted to support its obligations for target IDE397 / AMG 193 clinical combination expansion in NSCLC.
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Entered into an option and license agreement for a potential first-in-class B7H3/PTK7 topo-I-payload bispecific antibody drug conjugate (B7H3/PTK7 Topo-Payload BsADC)
program with Biocytogen Pharmaceuticals (Beijing) Co., Ltd. (Biocytogen) in July 2024. A development candidate nomination is targeted for the second half of 2024.
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IDEAYA plans to host an Investor R&D Day in Q4 2024.
Corporate Development

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Raised gross proceeds of approximately $302.4 million in July 2024 through public offering, generating net proceeds of approximately $283.8 million.
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Appointed Daniel A. Simon as Chief Business officer. Mr. Simon brings over 18 years of experience at leading life science and strategy consulting companies.

Clinical Programs and Upcoming Milestones

Darovasertib (IDE196) Program in Tumors with GNAQ or GNA11 Mutations

Darovasertib is a potent and selective protein kinase C (PKC) inhibitor being developed to broadly address primary and metastatic UM. Darovasertib is currently being evaluated in four ongoing clinical trials. The darovasertib and crizotinib combination in MUM has FDA Fast Track designation:

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IDE196-002(NCT05987332) is a Phase 2/3 potentially registration-enabling clinical trial of darovasertib + crizotinib in first-line human leukocyte antigens HLA-A2*02:01(-) MUM. Triple digit patient enrollment has been achieved as of July 31, 2024.
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IDE196-001 (NCT03947385) is a Phase 1/2 clinical trial evaluating darovasertib + crizotinib in GNAQ/11 melanomas, including in MUM and metastatic cutaneous melanoma.
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Phase 2 trials of darovasertib as neoadjuvant / adjuvant therapy in primary UM:
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IDE196-009 (NCT05907954) is a company-sponsored Phase 2 trial evaluating darovasertib as neoadjuvant treatment of UM prior to primary interventional treatment of enucleation or radiation therapy, and as adjuvant therapy following the primary treatment.
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Interim efficacy and safety results were reported in conjunction with the Phase 2 investigator-initiated trial (IST) interim data ASCO (Free ASCO Whitepaper) 2024 presentation.
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Data from eight patients (six enucleation and two plaque eligible) who have been on darovasertib treatment for 4 months or more as of the database lock of May 24, 2024 demonstrated a median tumor shrinkage (maximum height/base/volume change) of approximately 40%/25%/72% and the majority of the six enucleation patients had reported Eye Saved (i.e., converted to plaque brachytherapy or external beam radiotherapy (EBRT) eligible).
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Darovasertib had a manageable adverse events (AEs) profile with no drug-related serious adverse events (SAEs) observed; drug-related AEs were predominantly Grade 1 or Grade 2 and approximately 13% of patients reported at least one drug-related Grade 3 AE.
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The trial has enrolled over 50 patients in 20 sites globally, as of July 31, 2024.
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An amendment to the study protocol was submitted to the FDA in July 2024 to enable dosing of darovasertib as neoadjuvant and adjuvant therapy up to 12 months each. As part of this amendment the number of patients in the study was increased from 82 to 122 patients and the part 2 of the study will, once the amendment is effective, consist of adjuvant treatment with darovasertib in combination with crizotinib for patients with disease characteristics suggesting high or intermediate risk of metastasis.
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Additional clinical efficacy update from the company-sponsored Phase 2 of darovasertib neoadjuvant UM trial in over 30 patients is anticipated in the second half of 2024.
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NADOM (NCT05187884) is a Phase 2 neoadjuvant / adjuvant trial of darovasertib in ocular melanoma. This is an IST led by Anthony Joshua, MBBS, PhD, FRACP, Head Department of Medical Oncology, Kinghorn Cancer Centre, St. Vincent’s Hospital in Sydney with additional participating sites in Melbourne, Australia.
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Interim efficacy and safety results were presented at the ASCO (Free ASCO Whitepaper) 2024 meeting. As of the database lock on May 14, 2024, 13 patients had completed neoadjuvant treatment, 11 patients received adjuvant darovasertib after primary treatment of their UM, with five patients completing the planned six months of therapy. At that time, 75% (nine out of 12 enucleation patients) had confirmed Eye Saved (i.e., converted to plaque brachytherapy or EBRT). After six months, approximately 67% (eight out of 12 enucleation patients) observed greater than 30% tumor shrinkage (maximum volume change) and median tumor shrinkage (maximum volume change) was approximately 47%.
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Darovasertib monotherapy neoadjuvant treatment had a manageable AE profile with no drug-related SAEs observed. Drug-related AEs were predominantly Grade 1 or Grade 2 and 20% of patients reported at least one drug-related Grade 3 AE.
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IDEAYA has scheduled a Type C meeting with the FDA in the third quarter of 2024 to discuss a potential registrational trial for darovasertib in the neoadjuvant UM setting.

IDE397 Program in Tumors with MTAP Deletion

IDE397 is a potent and selective small molecule inhibitor targeting methionine adenosyltransferase 2 alpha (MAT2A) in patients having solid tumors with methylthioadenosine phosphorylase (MTAP) deletion. IDEAYA continues to focus on evaluating IDE397 in two trials in select monotherapy indications and in high conviction clinical combinations:

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IDE397-001 (NCT04794699) is a Phase 1/2 treatment study with monotherapy expansion in MTAP-deletion NSCLC and urothelial cancer. The estimated U.S. MTAP-deletion annual incidence in NSCLC and urothelial cancer is approximately 48,000 patients.
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Selected 30 mg as the move-forward expansion dose for IDE397 monotherapy in MTAP-deletion urothelial cancer and squamous NSCLC based on adverse event profile and preliminary clinical efficacy observed.
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Over 35 global clinical trial sites activated to enable rapid enrollment.
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Reported positive interim data from 18 evaluable MTAP-deletion urothelial and NSCLC patients by RECIST 1.1:
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~39% Overall Response Rate (ORR) observed with one complete response and six partial responses. Two partial responses were awaiting confirmation at the time of the update (July 8, 2024), and one urothelial cancer patient that had a 100% tumor reduction in the target lesion at the last CT-scan assessment has now been confirmed. The second adenocarcinoma NSCLC patient is still awaiting confirmation as of July 31, 2024
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In patients with urothelial cancer: One complete response and two partial responses were observed.
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In patients with lung cancer: three partial responses were seen in squamous NSCLC patients, and one partial response seen in adenocarcinoma NSCLC patient. There was one non-evaluable patient who discontinued due to rapid clinical progression of cancer fatigue and drug-unrelated adverse events in cycle 1 of treatment.
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~94% Disease Control Rate (DCR) seen with one complete response, six partial responses, and 10 stable disease.
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~78% of patients (14/18) experienced tumor shrinkage.
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Preliminary durability assessment showed 11 of the 18 patients are still on treatment, and five of seven RECIST 1.1 responses remain in response. Median duration of treatment, median duration of response, and median progression free survival not yet reached.
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~81% circulating tumor DNA (ctDNA) Molecular Response (MR) Rate observed in evaluable subjects with 13 of 16 patients with 50% or greater ctDNA reduction. There were several quality control failures of patient samples that led to unavailability for MR analysis.
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Overall favorable AE profile. Approximately 5.6% grade 3 or higher drug-related AEs and no drug-related SAEs reported at IDE397 30 mg once-a-day expansion dose. No drug-related AEs leading to discontinuations observed. We anticipate that the favorable AE profile and dosing convenience of a 30 mg once-a-day tablet has the potential to enable long-term dosing and combination development.
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30 mg once daily expansion dose achieves target drug coverage and plasma S-adenosyl-l-methionine (SAM) pharmacodynamic reduction associated with preclinical tumor regressions.
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Targeting development of IDE397 registrational plan in MTAP-deletion solid tumors in 2025.
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Phase 1/2 trial of IDE397 and AMG 193 in MTAP-Deletion NSCLC (Amgen-sponsored study, NCT05975073)
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Targeting development of joint publication strategy on IDE397 and AMG193 combination in 2024.
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At this time, the IDE397 / AMG 193 clinical combination dose escalation is ongoing. In the past quarter, IDEAYA, in consultation with Amgen, has now financially budgeted to support its obligations for target IDE397 / AMG 193 clinical combination expansion in NSCLC.
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First patient dosed in the Phase 1 trial of IDE397 and Trodelvy in MTAP-deletion urothelial cancer (IDEAYA-sponsored,NCT04794699) evaluating the safety, tolerability, pharmacokinetics, pharmacodynamics and efficacy. The MAT2A-Trop2 antibody-drug conjugate (ADC) combination targets two distinct, yet complementary nodes in the 26% of patients with MTAP-deleted urothelial cancer and has first-in-class potential to improve clinical outcomes for urothelial cancer patients.

IDE161 Program in Tumors with Homologous Recombination Deficiency

IDE161 is a potential first-in-class inhibitor of poly(ADP-ribose) glycohydrolase (PARG), a novel, mechanistically distinct target in the same clinically validated biological pathway as poly(ADP-ribose) polymerase (PARP). IDE161 received two FDA Fast Track designations in platinum-resistant advanced or metastatic ovarian cancer patients having tumors with BRCA1/2 mutations, and in pretreated advanced or metastatic HR+, Her2-, BRACA1/2 mutant breast cancer. IDE161 is currently being evaluated as a monotherapy in IDE161-001 (NCT05787587), a Phase 1 trial of IDE161 in solid tumors with homologous recombination deficiency (HRD). Selection of an initial Phase 1/2 monotherapy expansion dose in HRD solid tumors remains on track for the second half of 2024. IDEAYA is currently validating IDE161 combination opportunities preclinically and targeting identification of additional combination(s) in 2024.

Additionally, IDEAYA is planning to evaluate IDE161 in combination with KEYTRUDA in patients with microsatellite instability (MSI)-high and microsatellite stable (MSS) endometrial cancer. Clinical first-patient-in for the IDE161 and KEYTRUDA combination is targeted in the second half of 2024.

KEYTRUDA is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

GSK-Partnered Programs

GSK101 (IDE705) Program in Tumors with HRD

GSK101 (IDE705) is a potential first-in-class small molecule inhibitor of Pol Theta Helicase being developed as a combination treatment with niraparib for advanced solid tumors with HRD. The

dose escalation portion of the GSK-sponsored Phase 1/2 clinical trial to evaluate GSK101 in combination with niraparib, the GSK small molecule inhibitor of PARP, for patients having solid tumors with BRCA or other HR mutations, or with HRD is currently ongoing.

Upon initiation of the Phase 1 dose expansion, IDEAYA will be eligible to receive a $10.0 million milestone payment, with the collaboration having a potential further aggregate later-stage development and regulatory milestones of up to $465.0 million. GSK is responsible for all research and development costs for the program. Upon commercialization, IDEAYA will be eligible to receive up to $475 million of commercial milestones, and tiered royalties on global net sales of GSK101 – ranging from high single-digit to sub-teen double-digit percentages, subject to certain customary reductions.

Werner Helicase Inhibitor in Tumors with High MSI

IDEAYA and GSK remain on track for an IND filing in the second half of 2024 for the selected Werner Helicase inhibitor announced in December 2023. The IND-enabling Good Laboratory Practice (GLP) toxicology studies have been completed for the Werner Helicase inhibitor development candidate. IDEAYA has the potential to earn up to an additional $17.0 million in aggregate milestones through early Phase 1, including $7.0 million upon IND clearance, and is entitled to receive up to $465.0 million in further later-stage development and regulatory milestones. GSK is responsible for 80% of global research and development costs and IDEAYA is responsible for 20% of such costs. Upon commercialization, IDEAYA will be eligible to receive up to $475 million of commercial milestones, 50% of U.S. net profits and tiered royalties on global non-U.S. net sales of the Werner Helicase inhibitor development candidate (DC) – ranging from high single-digit to sub-teen double-digit percentages, subject to certain customary reductions.

B7H3/PTK7 Topo-Payload BsADC Program

IDEAYA entered into an option and license agreement for a potential first-in-class B7H3/PTK7 Topo-Payload BsADC program with Biocytogen in July 2024. The agreement grants IDEAYA an option for an exclusive worldwide license from Biocytogen for a potential first-in-class B7H3/PTK7 Topo-Payload BsADC program. B7H3/PTK7 has been found to be co-expressed in multiple solid tumor types, including double-digit percent prevalence in lung, colorectal, and head and neck cancers, among others. Based on preclinical data, the potential first-in-class B7H3/PTK7 Topo-Payload BsADC program has the potential to be developed as a monotherapy agent and used in combination with multiple programs in IDEAYA’s pipeline targeting DDR-based therapies, including PARG inhibitor IDE161. A development candidate nomination for the B7H3/PTK7 Topo-Payload BsADC program is targeted for the second half of 2024.

Under the terms of the agreement, Biocytogen will receive an upfront fee and, upon an option exercise by IDEAYA, be entitled to receive an option exercise fee, development and regulatory milestones and commercial milestone payments, as well as single-digit royalties on net sales. Total potential upfront, option exercise and milestone payments equal an aggregate of $406.5 million, including development and regulatory milestones of $100.0 million.

Next-Generation Precision Medicine Pipeline Programs

Early preclinical research programs focused on pharmacological inhibition of several new targets for patients with solid tumors characterized by defined biomarkers based on genetic mutations and/or molecular signatures are ongoing. These programs have the potential for discovery and development of first-in-class or best-in-class therapeutics with multiple wholly owned DC nominations targeted in the second half of 2024, including in MTAP-deletion solid tumors indications to enable a potential wholly-owned clinical combination with IDE397 and the lysine acetyltransferase 6 (KAT6) pathway.

Financial Results

As of June 30, 2024, IDEAYA had cash, cash equivalents and marketable securities totaling $952.7 million. This compared to cash, cash equivalents and marketable securities of $941.4 million as of March 31, 2024. The increase was primarily attributable to net proceeds of $36.5 million from the sale of common stock shares through IDEAYA’s at-the-market offering program during the period from April 1, 2024 to June 30, 2024, partially offset by net cash used in operations.

Subsequent to the reporting period for the quarter ended June 30, 2024, IDEAYA announced the closing in July 2024 of an underwritten public offering of common stock and pre-funded warrants to purchase common stock, generating net proceeds of approximately $283.8 million, after deducting the underwriting discounts and commissions and estimated offering expenses payable by IDEAYA.

There was no collaboration revenue recognized for the three months ended June 30, 2024 similar to the three months ended March 31, 2024. We completed all performance obligations related to the upfront payment under the GSK collaboration agreement as of December 31, 2023. Future collaboration revenue recognized under the GSK collaboration agreement will be related to future milestone payments as they are earned.

Research and development (R&D) expenses for the three months ended June 30, 2024 totaled $54.5 million compared to $42.8 million for the three months ended March 31, 2024. The increase was primarily due to higher stock-based compensation expenses, clinical trial expenses, professional and outside services and consulting expenses.

General and administrative (G&A) expenses for the three months ended June 30, 2024 totaled $10.4 million compared to $8.2 million for the three months ended March 31, 2024. The increase was primarily due to higher stock-based compensation expenses, audit fees and consulting expenses.

The net loss for the three months ended June 30, 2024 was $52.8 million compared to the net loss of $39.6 million for the three months ended March 31, 2024. Total stock compensation expense for the three months ended June 30, 2024 was $9.7 million compared to $6.3 million for the three months ended March 31, 2024.

On August 6, 2024 Heron Therapeutics, Inc. (Nasdaq: HRTX) ("Heron" or the "Company"), a commercial-stage biotechnology company, reported financial results for the three and six months ended June 30, 2024, and highlighted recent corporate updates (Press release, Heron Therapeutics, AUG 6, 2024, View Source [SID1234645420]).

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"We have had an exciting start to 2024 with many encouraging milestones that provide the foundation for ongoing commercial success. We are improving the financial efficiency of the business by growing revenues, improving margins, and reducing expenses. Regarding ZYNRELEF, we continue to expand our partnership with CrossLink and progress our regulatory activities in anticipation of a fourth quarter launch of the VAN," said Craig Collard, Chief Executive Officer of Heron.

Business Highlights

The range for adjusted operating expenses guidance for 2024 is being narrowed from $108.0 million to $116.0 million to a revised $107.0 million to $111.0 million. Additionally, the range for adjusted EBITDA guidance is being narrowed from $(22.0) million to $3.0 million to a revised $(10) million to $3.0 million.

The ZYNRELEF VAN PDUFA goal date is set for September 23, 2024. The VAN is designed to allow for easier and more efficient preparation and administration of ZYNRELEF in the operating room, with anticipated launch before year-end.

Our development program for the ZYNRELEF Prefilled Syringe ("PFS"), which will allow for immediate use of ZYNRELEF, continues to progress with an expected U.S. Food and Drug Administration ("FDA") submission for approval in 2026.

ZYNRELEF is included in the proposed 2025 NOPAIN Act under the Medicare hospital Outpatient Prospective Payment System ("OPPS") and the Medicare Ambulatory Surgical Center ("ASC") payment system (the "Proposed Rule") as a qualifying product effective April 1, 2025. The Proposed Rule’s April 1, 2025 effective date for ZYNRELEF is expected to allow ZYNRELEF to maintain separate reimbursement in the HOPD and ASC settings without disruption.

The training and integration of CrossLink sales representatives to promote ZYNRELEF to orthopedic surgeons continues its rapid progress. To date, 561 CrossLink sales representatives have completed training and are building the foundation for increased adoption.
Financial Guidance for 2024

The Company narrows its full-year 2024 guidance for Adjusted Operating Expenses and Adjusted EBITDA:

Product Revenues, Net

$138.0 to $158.0 million

Adjusted Operating Expenses

Original Revised

$108.0 to $116.0 million $107.0 to $111.0 million

Adjusted EBITDA

Original Revised

$(22.0) to $3.0 million $(10.0) to $3.0 million

Acute Care Franchise

Acute Care Franchise Net Product Sales: For the three and six months ended June 30, 2024, acute care franchise Net Product Sales were $6.8 million and $12.3 million, respectively, which increased from $4.5 million and $8.3 million, respectively, for the same period in 2023.

ZYNRELEF Net Product Sales: Net Product Sales of ZYNRELEF (bupivacaine and meloxicam) extended-release solution for the three and six months ended June 30, 2024 were $5.8 million and $10.8 million, respectively, which increased from $4.2 million and $7.7 million, respectively, for the same period in 2023.

APONVIE Net Product Sales: Net Product Sales of APONVIE for the three and six months ended June 30, 2024 were $1.0 million and $1.5 million, respectively, which increased from $0.3 million and $0.6 million, respectively, for the same period in 2023.
Oncology Care Franchise

Oncology Care Franchise Net Product Sales: For the three and six months ended June 30, 2024, oncology care franchise Net Product Sales were $29.2 million and $58.4 million, respectively, which increased from $27.3 million and $53.1 million for the same period in 2023.

CINVANTI Net Product Sales: Net Product Sales of CINVANTI (aprepitant) injectable emulsion for the three and six months ended June 30, 2024 were $24.9 million and $50.5 million, which increased from $24.5 million and $47.3 million for the same period in 2023.

SUSTOL Net Product Sales: Net Product Sales of SUSTOL (granisetron) extended-release injection for the three and six months ended June 30, 2024 were $4.3 million and $7.9 million, respectively, which increased from $2.8 million and $5.8 million, respectively, for the same period in 2023.
Conference Call and Webcast

Heron will host a conference call and webcast on August 6, 2024 at 4:30 p.m. ET. The conference call can be accessed by dialing (646) 307-1963 for domestic callers and (800) 715-9871 for international callers. Please provide the operator with the passcode 1737564 to join the conference call. The conference call will also be available via webcast under the Investor Relations section of Heron’s website at www.herontx.com. An archive of the teleconference and webcast will also be made available on Heron’s website for sixty days following the call.

About ZYNRELEF for Postoperative Pain

ZYNRELEF is the first and only dual-acting local anesthetic that delivers a fixed-dose combination of the local anesthetic bupivacaine and a low dose of nonsteroidal anti-inflammatory drug meloxicam. ZYNRELEF is the first and only extended-release local anesthetic to demonstrate in Phase 3 studies significantly reduced pain and significantly increased proportion of patients requiring no opioids through the first 72 hours following surgery compared to bupivacaine solution, the current standard-of-care local anesthetic for postoperative pain control. ZYNRELEF was initially approved by the FDA in May 2021 for use in adults for soft tissue or periarticular instillation to produce postsurgical analgesia for up to 72 hours after bunionectomy, open inguinal herniorrhaphy and total knee arthroplasty. In December 2021, the FDA approved an expansion of ZYNRELEF’s indication to include foot and ankle, small-to-medium open abdominal, and lower extremity total joint arthroplasty surgical procedures. On January 23, 2024, the FDA approved ZYNRELEF for soft tissue and orthopedic surgical procedures including foot and ankle, and other procedures in which direct exposure to articular cartilage is avoided. Safety and efficacy have not been established in highly vascular surgeries, such as intrathoracic, large multilevel spinal, and head and neck procedures.

Please see full prescribing information, including Boxed Warning, at www.ZYNRELEF.com.

About APONVIE for Postoperative Nausea and Vomiting (PONV)

APONVIE is a substance NK1 Receptor Antagonist (RA), indicated for the prevention of PONV in adults. Delivered via a 30-second IV push, APONVIE 32 mg was demonstrated to be bioequivalent to oral aprepitant 40 mg with rapid achievement of therapeutic drug levels. APONVIE is the same formulation as Heron’s approved drug product CINVANTI. APONVIE is supplied in a single-dose vial that delivers the full 32 mg dose for PONV. APONVIE was approved by the FDA in September 2022 and became commercially available in the U.S. on March 6, 2023.

Please see full prescribing information at www.APONVIE.com.

About CINVANTI for Chemotherapy Induced Nausea and Vomiting (CINV) Prevention

CINVANTI, in combination with other antiemetic agents, is indicated in adults for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy (HEC) including high-dose cisplatin as a single-dose regimen, delayed nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy (MEC) as a single-dose regimen, and nausea and vomiting associated with initial and repeat courses of MEC as a 3-day regimen. CINVANTI is an IV formulation of aprepitant, an NK1 RA. CINVANTI is the first IV formulation to directly deliver aprepitant, the active ingredient in EMEND capsules. Aprepitant (including its prodrug, fosaprepitant) is a single-agent NK1 RA to significantly reduce nausea and vomiting in both the acute phase (0–24 hours after chemotherapy) and the delayed phase (24–120 hours after chemotherapy). The FDA-approved dosing administration included in the U.S. prescribing information for CINVANTI include 100 mg or 130 mg administered as a 30-minute IV infusion or a 2-minute IV injection.

Please see full prescribing information at www.CINVANTI.com.

About SUSTOL for CINV Prevention

SUSTOL is indicated in combination with other antiemetics in adults for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of moderately emetogenic chemotherapy (MEC) or anthracycline and cyclophosphamide (AC) combination chemotherapy regimens. SUSTOL is an extended-release, injectable 5-hydroxytryptamine type 3 RA that utilizes Heron’s Biochronomer drug delivery technology to maintain therapeutic levels of granisetron for ≥5 days. The SUSTOL global Phase 3 development program was comprised of two, large, guideline-based clinical studies that evaluated SUSTOL’s efficacy and safety in more than 2,000 patients with cancer. SUSTOL’s efficacy in preventing nausea and vomiting was evaluated in both the acute phase (0–24 hours after chemotherapy) and delayed phase (24–120 hours after chemotherapy).

Please see full prescribing information at www.SUSTOL.com.

On August 6, 2024 FibroGen, Inc. (NASDAQ: FGEN) reported financial results for the second quarter 2024 and provided an update on the company’s recent developments (Press release, FibroGen, AUG 6, 2024, View Source [SID1234645419]).

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"While we are disappointed with the results from the pamrevlumab pancreatic cancer trials, we continue to be very excited about the prospects of FG-3246 and PET46, our CD46 targeted antibody-drug conjugate and companion PET imaging agent. We have released compelling Phase 1 data on FG-3246 as a monotherapy and in combination with enzalutamide in metastatic castration-resistant prostate cancer. In addition, roxadustat continues its strong momentum in China, exceeding $92 million in net sales in the second quarter," said Thane Wettig, Chief Executive Officer, FibroGen. "Looking ahead, we expect topline data from the Phase 2 portion of the FG-3246 + enzalutamide combination study in mCRPC in the first half of 2025 and plan on initiating our Phase 2 monotherapy study in mCRPC in the first quarter of 2025 with a more focused and streamlined organization. I would like to express my deepest gratitude to our FibroGen colleagues who have dedicated so much of their time and energy for the prospect of bringing much needed therapies to some of the most challenging and deadly diseases affecting humanity."

Recent Developments and Key Events of Second Quarter 2024:

Implementing significant cost reduction plan in the U.S.
Headcount in the U.S. will be reduced by approximately 75%.
Focusing R&D investment on FG-3246 and PET46, a first-in-class antibody-drug conjugate and companion PET imaging agent for mCRPC.
Announced positive interim results from the dose escalation portion of the investigator-sponsored Phase 1b/2 study conducted by the University of California San Francisco of FG-3246 (FOR46), a potential first-in-class anti-CD46 antibody drug conjugate (ADC) with a MMAE-containing payload, in combination with enzalutamide in patients with metastatic castration resistant prostate cancer (mCRPC) at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting.
The presentation included data from 17 biomarker unselected patients in the dose escalation portion of the trial. Over 70% of the patients in the study received at least two prior ARSIs, which included prior enzalutamide treatment.
The primary endpoint was determination of the maximally tolerated dose (MTD) of FG-3246 in combination with enzalutamide. The MTD was established at 2.1 mg/kg ABW, with primary G-CSF prophylaxis, in combination with enzalutamide 160 mg/day. The combination treatment demonstrated an encouraging preliminary estimate of median radiographic progression free survival (rPFS) of 10.2 months with prostate-specific antigen (PSA) declines observed in 71% (12/17) of evaluable patients.
Additional data from a total of 56 biomarker unselected and heavily pre-treated patients in a Phase 1 monotherapy study of FG-3246 in mCRPC reported.
Efficacy analysis (includes adenocarcinoma patients receiving doses ≥ 1.2 mg/kg):
The median radiographic progression free survival (rPFS) in this patient population was 8.7 months.
For RECIST evaluable patients, 20% met the criteria of a partial response, or measurable tumor reduction in size of ≥ 30%, with a median duration of response of 7.5 months.
PSA reductions of ≥ 50% were observed in 36% of PSA evaluable patients.
Safety analysis:
The most frequent adverse events were consistent with other MMAE-based antibody drug conjugates and included infusion-related reactions, fatigue, weight loss, neutropenia, and peripheral neuropathy.
Reported topline results from the pamrevlumab arm of PanCAN Precision Promise Phase 2/3 adaptive platform trial for the treatment of metastatic pancreatic ductal adenocarcinoma (mPDAC), in which the trial did not meet the primary endpoint.
Reported topline results from the LAPIS Phase 3 study of pamrevlumab in patients with locally advanced, unresectable pancreatic cancer (LAPC), in which the trial did not meet the primary endpoint.
Upcoming Milestones:

Roxadustat

Expect approval decision for roxadustat in chemotherapy-induced anemia (CIA) in China in the second half of 2024. If approved, FibroGen will receive a $10 million milestone payment from AstraZeneca.
Oncology Pipeline

Topline results from the Phase 2 portion of the investigator-sponsored Phase 1b/2 study conducted by the University of California San Francisco of FG-3246 in combination with enzalutamide in patients with mCRPC expected in 1H 2025.
Anticipate initiation of Phase 2 monotherapy dose optimization study of FG-3246 in mCRPC in 1Q 2025.
China:

Second quarter FibroGen net product revenue under U.S. GAAP from the sale of roxadustat in China was $49.6 million compared to $23.9 million in the first quarter of 2023, an increase of 108% year over year.
Second quarter total roxadustat net sales in China1 by FibroGen and the distribution entity jointly owned by FibroGen and AstraZeneca (JDE) was $92.3 million, compared to $76.4 million in the second quarter of 2023, an increase of 21% year over year, driven by a 33% increase in volume.
Roxadustat continues to be the number one brand based on value share in the anemia of CKD market in China.
For 2024, FibroGen’s expected full year net product revenue under U.S. GAAP is raised to a range between $135 million to $150 million, representing expected full year roxadustat net sales in China1 by FibroGen and the JDE of $320 million to $350 million, due to continued strong performance in China.
Financial:

Total revenue for the second quarter of 2024 was $50.6 million, as compared to $44.3 million for the second quarter of 2023, an increase of 14% year over year. Total revenue increase was driven by strong performance of roxadustat in China and changes in net product revenue assumptions under U.S. GAAP.
Net loss for the second quarter of 2024 was $15.5 million, or $0.16 net loss per basic and diluted share, compared to a net loss of $87.7 million, or $0.90 net loss per basic and diluted share one year ago.
At June 30, 2024, FibroGen reported $147.1 million in cash, cash equivalents and accounts receivable.
We expect our cash, cash equivalents and accounts receivable to be sufficient to fund our operating plans into 2026.
Conference Call and Webcast Details
FibroGen management will host a conference call and webcast today, Tuesday, August 6, 2024, at 5:00 PM Eastern Time to discuss financial results and provide a business update. Interested parties may access the conference call by dialing 1-877-300-8521 (in the U.S.) or 1-412-317-6026 (outside the U.S.). The call will be available via webcast by clicking here or on the "Events and Presentation" page on the FibroGen website.

About Roxadustat
Roxadustat, an oral medication, is the first in a new class of medicines comprising HIF-PH inhibitors that promote erythropoiesis, or red blood cell production, through increased endogenous production of erythropoietin, improved iron absorption and mobilization, and downregulation of hepcidin. Roxadustat is in clinical development for chemotherapy-induced anemia (CIA) and a Supplemental New Drug Application (sNDA) has been accepted by the China Health Authority.

Roxadustat is approved in China, Europe, Japan, and numerous other countries for the treatment of anemia of CKD in adult patients on dialysis (DD) and not on dialysis (NDD). Several other licensing applications for roxadustat have been submitted by partners, Astellas and AstraZeneca, to regulatory authorities across the globe, and are currently under review. Astellas and FibroGen are collaborating on the development and commercialization of roxadustat for the potential treatment of anemia in territories including Japan, Europe, Turkey, Russia, and the Commonwealth of Independent States, the Middle East, and South Africa. AstraZeneca and FibroGen continue to collaborate on the development and commercialization of roxadustat in China.

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.