On August 6, 2024 Karyopharm Therapeutics Inc. (Nasdaq: KPTI), a commercial-stage pharmaceutical company pioneering novel cancer therapies, reported financial results for the quarter ended June 30, 2024, and highlighted select corporate milestones and progress on its key clinical development programs (Press release, Karyopharm, AUG 6, 2024, View Source [SID1234645423]).

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"We are pleased with the strength of our commercial performance with consecutive quarter-over-quarter growth in the highly competitive multiple myeloma marketplace and look forward to leveraging the foundation that we have built in this indication to serve additional patients. Looking ahead with our improved capital structure following our debt refinancing and disciplined expense management, we are strongly positioned for our next stage of growth, to redefine the standard of care for patients with myelofibrosis and endometrial cancer, driven by selinexor’s growing body of compelling clinical and preclinical data in these indications," said Richard Paulson, President and Chief Executive Officer of Karyopharm.

Second Quarter 2024 and Recent Highlights

XPOVIO Commercial Performance

Achieved U.S. net product revenue of $28.0 million for the second quarter of 2024, compared to $26.0 million for the first quarter of 2024 and $28.5 million for the second quarter of 2023.

XPOVIO net product revenue was supported by quarter-over-quarter growth in both new patient starts and refills.

Continued quarter-over-quarter growth with > 10% growth in the community setting, which represents ~60% of overall net product revenues. In the academic setting, demand for XPOVIO was consistent quarter-over-quarter amidst ongoing competitive pressures, driven by the expanding use of XPOVIO immediately preceding and following T-cell therapies in later lines. The vast majority of XPOVIO new patient mix continues to be in the second to fourth lines of therapy.

Continued global momentum in the second quarter of 2024 with favorable reimbursement decisions in the United Kingdom and South Korea, and additional regulatory approvals in relapsed/refractory (R/R) DLBCL in mainland China and R/R multiple myeloma in multiple international markets.
Research and Development (R&D) Highlights

Myelofibrosis

Pre-clinical data were presented on the mechanism of action for XPO1 inhibition in myelofibrosis targeting multiple oncogenic pathways beyond JAK/STAT, including inhibition of NF-κB-driven proinflammatory cytokines and p53-mediated cell cycle regulation, at the June 2024 European Hematology Association (EHA) (Free EHA Whitepaper) meeting. These data suggest that XPO1 may be fundamental in myelofibrosis, providing the mechanistic rationale for both monotherapy as well as additive, if not synergistic, activity in combination with ruxolitinib, which we believe further supports the promising clinical results, including durable spleen volume reduction and symptom improvement, observed to date from the Phase 1 trial.

Pivotal SENTRY Phase 3 trial of selinexor in combination with ruxolitinib in JAK-naive myelofibrosis continues to enroll with strong momentum, supported by high interest from investigators and minimal competition from other therapies in the JAK-naïve setting; expected top-line data readout on track for 2H 2025.
Endometrial Cancer

Long-term follow-up data from a pre-specified exploratory subgroup analysis of patients with advanced or recurrent TP53 wild-type endometrial cancer from the SIENDO study (NCT03555422) were presented at "ASCO Plenary Series: Rapid Abstract Updates" oral session at the ASCO (Free ASCO Whitepaper) Annual Meeting in June 2024.

In the exploratory subgroup analysis from the Phase 3 SIENDO Study, 113 patients with TP53 wild-type advanced/recurrent endometrial cancer were randomized to receive selinexor (n=77) vs placebo (n=36) as maintenance therapy after 1L platinum-based chemotherapy. As of the April 1, 2024 data cut-off date, and a median duration of follow-up of 36.8 months, selinexor-treated patients had a median PFS of 28.4 months compared to 5.2 months for patients receiving placebo. In selinexor-treated patients with TP53 wild-type/pMMR and TP53 wild-type/dMMR endometrial cancer, the median PFS was 39.5 months and 13.1 months compared to 4.9 months and 3.7 months in those treated with placebo, respectively. Although immature, overall survival (OS) in the TP53 wild-type subgroup was promising, with a hazard ratio of 0.65; median OS for selinexor has not been reached as of the data cut-off date. No new safety signals were identified as of the data cut-off date of April 1, 2024. The most common treatment-emergent adverse events in selinexor treated TP53 wild-type patients were nausea (90%), vomiting (60%) and diarrhea (45%), the majority of which were grades 1-2.

The updated SIENDO analysis also highlighted findings from an exploratory quality-adjusted time without symptoms or toxicity analysis (Q-TWiST) used to assess quality and toxicity-adjusted PFS. The findings showed the restricted mean Q-TWiST for selinexor to be 26 months compared to 15 months for placebo, resulting in a difference of nearly 11 months.

Pivotal XPORT-EC-042 Phase 3 trial in TP53 wild-type endometrial cancer is now expected to read-out top-line data in early 2026, primarily due to higher-than-expected screen failure rates.
Multiple Myeloma

Updated clinical data on SPd (selinexor in combination with pomalidomide and dexamethasone) regimen from STOMP and MM-028 trials were published in the Frontiers of Oncology Journal in May 2024. Both the Phase 1b/2 Selinexor and Backbone Treatments of Myeloma Patients (STOMP) trial (NCT02343042) and the Phase 2b XPORT-MM-028 (NCT04414475) trials are evaluating multiple selinexor combinations, including SPd, in patients with relapsed or refractory multiple myeloma (RRMM). The updated results for SPd 40 mg from these studies showed a median PFS of 18.4 months and a manageable safety profile with no new safety signals.

Pivotal XPORT-MM-031 (EMN29) Phase 3 trial, an oral combination of selinexor 40 mg, pomalidomide and dexamethasone in patients with previously treated multiple myeloma, is enrolling patients at a lower rate than expected in an increasingly global competitive clinical trial environment targeting a similar patient population. Given this evolving environment and the positive SPd 40 mg PFS data published from the STOMP and MM-028 trials, Karyopharm intends to work with the trial’s sponsor, the European Myeloma Network, to amend certain aspects of the design for this trial, including a reduction in the number of patients that are targeted for enrollment, and the statistical plan. With these updates, Karyopharm expects top-line data readout in 1H 2025; there remains a potential to seek regulatory approval pending the outcome of the study results.
KPT-9274 (Padnarsertib)

KPT-9274, a first-in-class, oral small molecule and a dual inhibitor of PAK4 and NAMPT that was discovered at Karyopharm, was granted two Rare Pediatric Disease Designations (RPDD) by the U.S. Food and Drug Administration (FDA) for the treatment of Rhabdomyosarcoma (RMS) and for the treatment of Ewing sarcoma (EWS) in June 2024. The FDA further granted KPT-9274 two Orphan Drug Designations in July 2024 for the treatment of soft tissue sarcoma, which includes RMS, and for the treatment of EWS. RMS and EWS are rare cancers of the bone or soft tissue, primarily diagnosed in pediatric patients, with poor survival outcomes and high unmet need for new therapies. KPT-9274 showed tumor regressions and decreased metastatic properties in pediatric RMS and EWS pre-clinical models. Karyopharm is evaluating out-licensing and/or partnership opportunities for further advancement of this program.
Financing Transactions and 2024 Financial Outlook

In May 2024, the Company completed certain financing transactions which extended the vast majority of its debt maturities into 2028 and 2029 and amended its royalty agreement with HealthCare Royalty, further strengthening its balance sheet.
Based on its current operating plans, Karyopharm has updated its guidance for full year 2024 as follows:

Total revenue to be in the range of $145.0 million to $160.0 million as compared to initial guidance of $140.0 million to $160.0 million. Total revenue consists of U.S. XPOVIO net product revenue and license, royalty and milestone revenue earned from partners.

U.S. XPOVIO net product revenue to be in the range of $105.0 million to $120.0 million as compared to initial guidance of $100.0 million to $120.0 million.

R&D and selling, general and administrative (SG&A) expenses to be in the range of $250.0 million to $265.0 million, which includes approximately $20.0 million estimated non-cash stock-based compensation expense, as compared to initial guidance of $260.0 million to $280.0 million including $20.0 million to $25.0 million of estimated non-cash stock-based compensation expense.

The Company expects that its existing cash, cash equivalents and investments, and the revenue it expects to generate from XPOVIO net product sales, as well as revenue generated from its license agreements, will be sufficient to fund its planned operations into the first quarter of 20261 aided by ongoing disciplined expense management and initiated cost saving measures.
1 Excluding re-payment of $24.5 million aggregate principal amount of the Company’s remaining senior convertible notes due 2025 and $25.0 million minimum liquidity covenant under the senior secured term loan due 2028.

Second Quarter 2024 Financial Results

Total revenue: Total revenue for the second quarter of 2024 was $42.8 million, compared to $37.6 million for the second quarter of 2023.

Net product revenue: Net product revenue for the second quarter of 2024 was $28.0 million, compared to $28.5 million for the second quarter of 2023.

License and other revenue: License and other revenue for the second quarter of 2024 was $14.8 million, compared to $9.1 million for the second quarter of 2023. The increase was primarily due to $4.0 million of milestone-related revenue recognized from Menarini in 2024 and a $2.3 million increase in revenue for the reimbursement of development-related expenses from Menarini due to an increase in the corresponding expenses.

Cost of sales: Cost of sales for the second quarter of 2024 was $1.5 million, compared to $1.2 million for the second quarter of 2023. Cost of sales reflects the costs of XPOVIO units sold and the costs of products sold to our partners.

R&D expenses: R&D expenses for the second quarter of 2024 were $38.4 million, compared to $31.5 million for the second quarter of 2023. The increase was primarily due to an increase in clinical trial and related costs, related mainly to increased activity in our ongoing pivotal Phase 3 trials in myelofibrosis and multiple myeloma, including increased purchases of comparator drugs.

SG&A expenses: SG&A expenses for the second quarter of 2024 were $31.1 million, compared to $34.5 million for the second quarter of 2023. The decrease was primarily due to our ongoing cost reduction initiatives and lower headcount.

Interest income: Interest income for the second quarter of 2024 was $1.9 million, compared to $2.8 million for the second quarter of 2023.

Interest expense: Interest expense for the second quarter of 2024 was $8.9 million, compared to $5.8 million for the second quarter of 2023. The increase in interest expense was due to the Company’s new term loan and new secured convertible senior notes.

Gain on extinguishment of debt and other income: The Company recognized a non-cash gain on extinguishment of debt of $44.7 million and other income of $14.3 million during the second quarter of 2024, which related to the refinancing transactions that were completed during the second quarter of 2024.

Net income (loss): Karyopharm reported net income of $23.8 million, or $0.15 income per basic share and $0.20 loss per diluted share, for the second quarter of 2024, compared to a net loss of $32.6 million, or $0.29 loss per basic and diluted share, for the second quarter of 2023.

Cash position: Cash, cash equivalents, restricted cash and investments as of June 30, 2024 totaled $152.5 million, compared to $192.4 million as of December 31, 2023.

Conference Call Information

Karyopharm will host a conference call today, August 6, 2024, at 8:00 a.m. Eastern Time, to discuss the second quarter 2024 financial results and provide business highlights. To access the conference call, please dial (800) 836-8184 (local) or (646) 357-8785 (international) at least 10 minutes prior to the start time and ask to be joined into the Karyopharm Therapeutics call. A live audio webcast of the call, along with accompanying slides, will be available under "Events & Presentations" in the Investor section of the Company’s website. An archived webcast will be available on the Company’s website approximately two hours after the event.

About XPOVIO (selinexor)

XPOVIO is a first-in-class, oral exportin 1 (XPO1) inhibitor and the first of Karyopharm’s Selective Inhibitor of Nuclear Export (SINE) compounds for the treatment of cancer. XPOVIO functions by selectively binding to and inhibiting the nuclear export protein XPO1. XPOVIO is approved in the U.S. and marketed by Karyopharm in multiple oncology indications, including: (i) in combination with VELCADE (bortezomib) and dexamethasone (XVd) in patients with multiple myeloma after at least one prior therapy; (ii) in combination with dexamethasone in patients with heavily pre-treated multiple myeloma; and (iii) in patients with diffuse large B-cell lymphoma (DLBCL), including DLBCL arising from follicular lymphoma, after at least two lines of systemic therapy. XPOVIO (also known as NEXPOVIO in certain countries) has received regulatory approvals in a growing number of ex-U.S. territories and countries, including Europe, the United Kingdom, China, South Korea and Israel, and is marketed in those areas by Karyopharm’s global partners. Selinexor is also being investigated in several other mid- and late-stage clinical trials across multiple high unmet need cancer indications, including in endometrial cancer and myelofibrosis.

For more information about Karyopharm’s products or clinical trials, please contact the Medical Information department at: Tel: +1 (888) 209-9326; Email: [email protected]

XPOVIO (selinexor) is a prescription medicine approved:

In combination with bortezomib and dexamethasone for the treatment of adult patients with multiple myeloma who have received at least one prior therapy (XVd).

In combination with dexamethasone for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors, at least two immunomodulatory agents, and an anti‐CD38 monoclonal antibody (Xd).

For the treatment of adult patients with relapsed or refractory diffuse large B‐cell lymphoma (DLBCL), not otherwise specified, including DLBCL arising from follicular lymphoma, after at least two lines of systemic therapy. This indication is approved under accelerated approval based on response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s).
SELECT IMPORTANT SAFETY INFORMATION

Warnings and Precautions

Thrombocytopenia: Monitor platelet counts throughout treatment. Manage with dose interruption and/or reduction and supportive care.
Neutropenia: Monitor neutrophil counts throughout treatment. Manage with dose interruption and/or reduction and granulocyte colony‐stimulating factors.
Gastrointestinal Toxicity: Nausea, vomiting, diarrhea, anorexia, and weight loss may occur. Provide antiemetic prophylaxis. Manage with dose interruption and/or reduction, antiemetics, and supportive care.
Hyponatremia: Monitor serum sodium levels throughout treatment. Correct for concurrent hyperglycemia and high serum paraprotein levels. Manage with dose interruption, reduction, or discontinuation, and supportive care.
Serious Infection: Monitor for infection and treat promptly.
Neurological Toxicity: Advise patients to refrain from driving and engaging in hazardous occupations or activities until neurological toxicity resolves. Optimize hydration status and concomitant medications to avoid dizziness or mental status changes.
Embryo‐Fetal Toxicity: Can cause fetal harm. Advise females of reproductive potential and males with a female partner of reproductive potential, of the potential risk to a fetus and use of effective contraception.
Cataract: Cataracts may develop or progress. Treatment of cataracts usually requires surgical removal of the cataract.
Adverse Reactions

The most common adverse reactions (≥20%) in patients with multiple myeloma who receive XVd are fatigue, nausea, decreased appetite, diarrhea, peripheral neuropathy, upper respiratory tract infection, decreased weight, cataract and vomiting. Grade 3‐4 laboratory abnormalities (≥10%) are thrombocytopenia, lymphopenia, hypophosphatemia, anemia, hyponatremia and neutropenia. In the BOSTON trial, fatal adverse reactions occurred in 6% of patients within 30 days of last treatment. Serious adverse reactions occurred in 52% of patients. Treatment discontinuation rate due to adverse reactions was 19%.

The most common adverse reactions (≥20%) in patients with multiple myeloma who receive Xd are thrombocytopenia, fatigue, nausea, anemia, decreased appetite, decreased weight, diarrhea, vomiting, hyponatremia, neutropenia, leukopenia, constipation, dyspnea and upper respiratory tract infection. In the STORM trial, fatal adverse reactions occurred in 9% of patients. Serious adverse reactions occurred in 58% of patients. Treatment discontinuation rate due to adverse reactions was 27%.

The most common adverse reactions (incidence ≥20%) in patients with DLBCL, excluding laboratory abnormalities, are fatigue, nausea, diarrhea, appetite decrease, weight decrease, constipation, vomiting, and pyrexia. Grade 3‐4 laboratory abnormalities (≥15%) are thrombocytopenia, lymphopenia, neutropenia, anemia, and hyponatremia. In the SADAL trial, fatal adverse reactions occurred in 3.7% of patients within 30 days, and 5% of patients within 60 days of last treatment; the most frequent fatal adverse reactions was infection (4.5% of patients). Serious adverse reactions occurred in 46% of patients; the most frequent serious adverse reaction was infection (21% of patients). Discontinuation due to adverse reactions occurred in 17% of patients.
Use In Specific Populations
Lactation: Advise not to breastfeed.

For additional product information, including full prescribing information, please visit www.XPOVIO.com.

To report SUSPECTED ADVERSE REACTIONS, contact Karyopharm Therapeutics Inc. at 1‐888‐209‐9326 or FDA at 1‐800‐FDA‐1088 or www.fda.gov/medwatch.

On August 6, 2024 Immunotherapy company ImmunityBio, Inc. (NASDAQ: IBRX), reported the opening of a clinical trial to study ANKTIVA (nogapendekin alfa inbakicept-pmln) together with the investigational AdHER2DC vaccine (autologous dendritic cells transduced with HER2 expressing adenovirus), in individuals with HER2-expressing endometrial cancer (Press release, ImmunityBio, AUG 6, 2024, View Source [SID1234645422]). It marks the latest trial involving ANKTIVA, the company’s IL-15 superagonist immune enhancer, to evaluate ANKTIVA as an agent to replace the short-term activity of checkpoint inhibitor immunotherapies with long-term effectiveness. ANKTIVA was recently approved by the FDA for BCG-unresponsive non-muscle invasive bladder cancer CIS with or without papillary tumors.

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This Phase 1/2 QUILT 502 trial (NCT06253494) sponsored by the National Cancer Institute, part of the National Institutes of Health, will study whether the AdHER2DC vaccine in combination with ANKTIVA, pembrolizumab (checkpoint inhibitor), and lenvatinib (kinase inhibitor) can be safely administered in combination and provide preliminary clinical efficacy before a larger, more definitive study.

Endometrial cancer is the most common gynecological cancer in the U.S., and affects more than 65,000 women each year with incidence peaking around 50-60 years of age. The 5-year overall survival rate in patients with metastasis is around 20 percent; treatment options after the second-line treatment are limited.

The AdHER2DC vaccine targets the HER2 protein, which is elevated in 30% of patients with endometrial cancer and in more than 50% of high risk subtypes. The AdHER2DCs are autologous, using each participant’s own blood cells obtained through apheresis, a "loop" where blood is removed from one vein, passed through a machine to filter out target cells and then returned to the patient through another vein. The AdHER2DC is a proprietary agent of the NCI and it will be manufactured at the NIH Clinical Center for each study participant. The single agent AdHER2DC demonstrated safety profile and immunogenicity in a phase 1 clinical trial conducted by the NCI. The first treatment cycle is 28 days and each cycle after that will be 21 days. All participants will receive the vaccine and the two FDA approved drugs pembrolizumab and lenvatinib, and some participants will receive ANKTIVA.

Phase 1 of the open-label, two-arm Phase 1/2 study will determine recommended dose of pembrolizumab, lenvatinib, ANKTIVA and AdHER2DC in participants with HER2 positive endometrial cancer. The Phase 2 portion of the study will assess the efficacy of the combination of pembrolizumab, lenvatinib, ANKTIVA and the AdHER2DC vaccine in qualified participants as determined by the proportion of participants without disease progression at six months. The study will enroll 60 subjects and is expected to be completed in 2026.

"We are pleased to partner with the NCI on this important cancer control study involving ANKTIVA, which has demonstrated in clinical trials that activation of memory T cells may help deliver long-duration response well beyond that of checkpoint inhibitors alone," said Patrick Soon-Shiong, M.D., Executive Chairman and Global Chief Scientific and Medical Officer at ImmunityBio. "We are hopeful that the AdHER2DC investigational vaccine plus ANKTIVA will ‘rescue’ the checkpoint inhibitor pembrolizumab and kinase inhibitor lenvatinib and lead to an improved response compared with the current standard of care in this high risk population."

ImmunityBio is already partnered with the NCI to study the use of ANKTIVA in cases of Lynch syndrome, a genetic condition that is linked with significantly increased incidence of cancers, particularly colon cancer. These studies along with the recent approval of ANKTIVA for bladder cancer signal the advent of the era of cytokines as the next-generation of immunotherapies.

To learn more about this study, please visit View Source

For patients interested in enrolling in this study, please contact NCI’s toll-free number 1-800-4-Cancer (1-800-422-6237) (TTY: 1-800-332-8615) and/or the website: View Source and/or [email protected].

The AdHER2DC vaccine is investigational. Safety and efficacy of this investigational agent have not been established by any health authority, including the FDA.

How ANKTIVA Works

The cytokine interleukin-15 (IL-15) plays a crucial role in the immune system by affecting the development, maintenance, and function of key immune cells—NK and CD8+ killer T cells—that are involved in killing cancer cells. By activating NK cells, ANKTIVA overcomes the tumor escape phase of clones resistant to T cells and restores memory T cell activity with resultant prolonged duration of complete response.

ANKTIVA is a first-in-class IL-15 agonist IgG1 fusion complex, consisting of an IL-15 mutant (IL-15N72D) fused with an IL-15 receptor alpha, which binds with high affinity to IL-15 receptors on NK, CD4+, and CD8+ T cells. This fusion complex of ANKTIVA mimics the natural biological properties of the membrane-bound IL-15 receptor alpha, delivering IL-15 by dendritic cells and drives the activation and proliferation of NK cells with the generation of memory killer T cells that have retained immune memory against these tumor clones. The proliferation of the trifecta of these immune killing cells and the activation of trained immune memory results in immunogenic cell death, inducing a state of equilibrium with durable complete responses. ANKTIVA has improved pharmacokinetic properties, longer persistence in lymphoid tissues, and enhanced anti-tumor activity compared to native, non-complexed IL-15 in-vivo.

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:

•
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.
o
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.
o
Over 35 global clinical trial sites activated to enable rapid enrollment.
o
Reported positive interim data from 18 evaluable MTAP-deletion urothelial and NSCLC patients by RECIST 1.1:
▪
~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
•
In patients with urothelial cancer: One complete response and two partial responses were observed.
•
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.
▪
~94% Disease Control Rate (DCR) seen with one complete response, six partial responses, and 10 stable disease.
▪
~78% of patients (14/18) experienced tumor shrinkage.
▪
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.
▪
~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.
▪
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.
▪
30 mg once daily expansion dose achieves target drug coverage and plasma S-adenosyl-l-methionine (SAM) pharmacodynamic reduction associated with preclinical tumor regressions.
o
Targeting development of IDE397 registrational plan in MTAP-deletion solid tumors in 2025.
•
Phase 1/2 trial of IDE397 and AMG 193 in MTAP-Deletion NSCLC (Amgen-sponsored study, NCT05975073)
o
Targeting development of joint publication strategy on IDE397 and AMG193 combination in 2024.
o
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.
•
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.