On August 8, 2024 Kura Oncology, Inc. (Nasdaq: KURA), a clinical-stage biopharmaceutical company committed to realizing the promise of precision medicines for the treatment of cancer, reported second quarter 2024 financial results and provided a corporate update (Press release, Kura Oncology, AUG 8, 2024, View Source [SID1234645611]).

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"This past quarter was highlighted by strong execution across the organization," said Troy Wilson, Ph.D., J.D., President and Chief Executive Officer of Kura Oncology. "We completed enrollment in our KOMET-001 registration-directed trial of ziftomenib in patients with relapsed/refractory (R/R) NPM1-mutant acute myeloid leukemia (AML), and we were delighted to have ziftomenib receive Breakthrough Therapy Designation from the FDA in that indication. In the KOMET-007 study, the safety, tolerability and clinical activity of ziftomenib continue to support advancement of ziftomenib into the frontline (1L) population, and the Phase 1b expansion study in combination with venetoclax and azacitidine (ven/aza) and cytarabine plus daunorubicin (7+3) is now open for enrollment. We are generating a robust clinical data package to support the broad development of ziftomenib, including enrollment of more than 100 patients in the KOMET-007 study, and we look forward to providing an update on this study at a medical meeting later this year, followed by topline data from our registration-directed trial in early 2025."

Recent Highlights

Completion of enrollment in pivotal trial of ziftomenib in R/R NPM1-mutant AML – In May 2024, Kura completed enrollment of 85 patients in the Phase 2 portion of KOMET-001, a registration-directed clinical trial of its menin inhibitor, ziftomenib, in patients with R/R NPM1-mutant AML. NPM1-mutant AML accounts for approximately 30% of new AML cases annually and represents a disease of significant unmet need for which no approved targeted therapy exists. The Company expects to report topline data from the trial in early 2025.
Breakthrough Therapy Designation for ziftomenib in NPM1-mutant AML – In April 2024, the U.S. Food and Drug Administration (FDA) granted Breakthrough Therapy Designation (BTD) to ziftomenib for the treatment of R/R NPM1-mutant AML. FDA granted BTD based on data from the KOMET-001 trial of ziftomenib in patients with R/R NPM1-mutant AML. BTD is awarded for a drug that treats a serious or life-threatening condition and may demonstrate substantial improvement on one or more clinically significant endpoints over available therapies.
Phase 1b expansion portion of KOMET-007 open for enrollment – Kura recently began dosing patients in the Phase 1b expansion portion of its KOMET-007 combination study of ziftomenib. The Phase 1b expansion study includes multiple combination cohorts, including ven/aza in newly diagnosed NPM1-mutant or KMT2A-rearranged AML and 7+3 in newly diagnosed NPM1-mutant or KMT2A-rearranged AML without qualification for high-risk disease. Each combination cohort is expected to enroll approximately 20 patients at 600 mg. The Company expects to present updated data from the KOMET-007 study at a medical meeting in the fourth quarter of 2024.
IND for ziftomenib in GIST; proof-of-concept study to begin in early 2025 – Earlier today, Kura announced FDA clearance of its IND application for ziftomenib for the treatment of advanced gastrointestinal stromal tumors (GIST) in combination with imatinib. Preclinical data suggest ziftomenib has potential to resensitize patients to imatinib and induce deep, durable responses. The Company expects to present the preclinical data for the combination at an upcoming scientific meeting, followed by a proof-of-concept study evaluating ziftomenib and imatinib in patients with advanced GIST in the first half of 2025.
Preclinical data support potential for menin inhibitor in diabetes – In June 2024, Kura reported data showing that ziftomenib induces insulin production, improves insulin sensitivity and reduces insulin resistance in a preclinical in vivo model of type 2 diabetes. Ziftomenib demonstrated meaningful levels of glycemic control, including reduced fasting blood glucose levels and %HbA1C within 27 days, as well as consistent improvement in both insulin sensitivity and insulin production. The data were presented at the American Diabetes Association (ADA) Scientific Sessions in Orlando. The Company expects to nominate the first in a series of next-generation development candidates targeting diabetes in early 2025.
First patient dosed in study of KO-2806 and adagrasib in KRASG12C-mutated NSCLC – Kura recently began dosing patients in its study of KO-2806, a next-generation farnesyl transferase inhibitor (FTI), in combination with adagrasib in KRASG12C-mutated non-small cell lung cancer (NSCLC). The Company’s findings suggest that combining KO-2806 with adagrasib may drive tumor regressions and enhance both duration and depth of antitumor response in preclinical models of KRASG12C-mutated NSCLC. The study of KO-2806 and adagrasib is supported by a clinical collaboration and supply agreement with Mirati, now a Bristol Myers Squibb company.
Financial Results

Research and development expenses for the second quarter of 2024 were $39.7 million, compared to $28.2 million for the second quarter of 2023.
General and administrative expenses for the second quarter of 2024 were $16.7 million, compared to $11.8 million for the second quarter of 2023.
Net loss for the second quarter of 2024 was $50.8 million, compared to a net loss of $37.2 million for the second quarter of 2023. This included non-cash share-based compensation expense of $8.4 million, compared to $7.0 million for the same period in 2023.
As of June 30, 2024, Kura had cash, cash equivalents and short-term investments of $491.5 million, compared to $424.0 million as of December 31, 2023.
Based on its operating plan, management expects that cash, cash equivalents and short-term investments will fund current operations into 2027.
Forecasted Milestones

Present updated data from the KOMET-007 trial of ziftomenib in combination with ven/aza and 7+3 at a medical meeting in the fourth quarter of 2024.
Report topline data from the KOMET-001 registration-directed trial of ziftomenib in NPM1-mutant R/R AML in early 2025.
Present preclinical data supporting opportunity for ziftomenib in GIST at a scientific meeting in the second half of 2024.
Initiate proof-of-concept study evaluating ziftomenib and imatinib in patients with advanced GIST in the first half of 2025.
Nominate a next generation menin inhibitor development candidate in early 2025.
Identify the maximum tolerated dose for KO-2806 as a monotherapy in the second half of 2024.
Complete enrollment of two expansion cohorts in KURRENT-HN and identify the optimal biologically active dose of tipifarnib and alpelisib by the end of 2024.
Present data from the KURRENT-HN trial of tipifarnib in combination with alpelisib in PIK3CA-dependent head and neck squamous cell carcinoma (HNSCC) in the first half of 2025.
Conference Call and Webcast

Kura’s management will host a webcast and conference call at 4:30 p.m. ET / 1:30 p.m. PT today, August 8, 2024, to discuss the financial results for the second quarter 2024 and to provide a corporate update. The live call may be accessed by dialing (877) 300-8521 for domestic callers and (412) 317-6026 for international callers and entering the conference ID: 10190278. A live webcast and archive of the call will be available online from the investor relations section of the company website at www.kuraoncology.com.

On August 8, 2024 Kronos Bio, Inc. (Nasdaq: KRON), a company dedicated to developing small molecule therapeutics that address cancers and other diseases driven by deregulated transcription, reported recent business progress and financial results for the second quarter of 2024 (Press release, Kronos Bio, AUG 8, 2024, View Source [SID1234645610]).

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"We continue to make great progress, both in the clinic and in expanding our pipeline targeting deregulated transcription. We are on track to share a clinical update on istisociclib in platinum-resistant high-grade serous ovarian cancer patients in the first half of 2025," said Nobert Bischofberger, Ph.D., president and chief executive officer of Kronos Bio. "In addition, we expect to dose our first relapsed/refractory multiple myeloma patient with KB-9558 in the first half of 2025 and are excited to announce HPV-driven tumors as another potential program for KB-9558. Our collaboration with Genentech and our internal discovery programs, including a new p300 program focused on autoimmune indications, continue to advance and we look forward to sharing our progress later this year."

Company and Pipeline Updates

Deborah Knobelman, Ph.D., appointed as chief operating officer and chief financial officer
•Dr. Knobelman joined the Company on June 3, 2024 and oversees the finance, accounting, business development, investor relations and corporate strategy functions.

Istisociclib (KB-0742), a CDK9 inhibitor for platinum-resistant high-grade serous ovarian cancer
•Istisociclib cleared the 80mg four-days-on, three-days-off dose and schedule, and the first patient with platinum-resistant high-grade serous ovarian cancer was enrolled in July (link to press release); data expected in first half of 2025.
•At American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) in June 2024, the Company presented updated study data from KB-0742-1001, the ongoing Phase 1/2 trial of istisociclib (KB-0742), an oral CDK9 inhibitor in relapsed or refractory transcriptionally addicted advanced solid tumors (link to poster).

KB-9558, a p300 lysine acetyltransferase (KAT) inhibitor for oncology indications
•p300 was identified as a critical cofactor of the interferon regulatory factor 4 (IRF4) transcription regulatory network in multiple myeloma, which led to the discovery of KB-9558, an inhibitor of the lysine acetyltransferase (KAT) domain of p300.
•Development of KB-9558 remains on track to complete IND-enabling studies in 2024 and the Company expects to enroll the first patient in a dose escalation study in relapsed/refractory multiple myeloma in the first half of 2025.

•Today the Company announced an additional opportunity for the potential use of KB-9558 in HPV-driven tumors. Data supporting p300 KAT inhibition in HPV-driven tumors will be presented later this year.

Novel p300 KAT inhibitor for autoimmune indications
•Given the role of IRF4 and p300 in B cells, T cells and other immune cells, the Company has begun exploring the utility of a p300 KAT inhibitor for autoimmune indications. The Company expects to provide an update on the role of p300 in inflammatory indications and announce a development candidate by the end of the year.

Second Quarter 2024 Financial Highlights

•Cash, cash equivalents and investments: With its ongoing and currently planned clinical programs and $136.6 million in cash, cash equivalents and investments as of June 30, 2024, the Company anticipates sufficient resources to fund its planned operations into the second half of 2026.

•R&D expenses: Research and development expenses were $13.8 million for the second quarter of 2024, which includes non-cash stock-based compensation expense of $0.8 million.

•G&A expenses: General and administrative expenses were $6.4 million for the second quarter of 2024, which includes non-cash stock-based compensation expense of $1.4 million.

•Impairment of long-lived assets and restructuring: For the second quarter of 2024, the Company incurred impairment of long-lived assets expense of $0.5 million and restructuring expense of less than $0.1 million.

•Net loss: Net loss for the second quarter of 2024 was $16.2 million, or $0.27 per share, including non-cash stock-based compensation expense of $2.2 million.

On August 8, 2024 Iovance Biotherapeutics, Inc. (NASDAQ: IOVA), a commercial biotechnology company focused on innovating, developing, and delivering novel polyclonal tumor infiltrating lymphocyte (TIL) therapies for patients with cancer, reported second quarter and first half 2024 financial results and corporate updates (Press release, Iovance Biotherapeutics, AUG 8, 2024, View Source [SID1234645609]).

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Frederick Vogt, Ph.D., J.D., Interim President and Chief Executive Officer of Iovance, stated, "The first half of 2024 ushered in our first FDA approval and the start of our U.S. commercial launch of Amtagvi for patients with previously treated advanced melanoma. Amtagvi and Proleukin demand remains strong and continues to increase as authorized treatment centers (ATCs) adopt Amtagvi and community referral networks are mobilized to drive patients to ATCs. These demand trends, as well as broader utilization of Amtagvi among an expanding ATC network, are expected to accelerate quarterly growth throughout this year and next year. We expect this growth to continue in 2025, 2026 and beyond. Additionally, we continue to expand our global commercial footprint, proprietary manufacturing capabilities, and broad clinical pipeline. As a fully integrated company, Iovance is well positioned to remain the global leader in innovating, developing, and delivering TIL cell therapy for patients with cancer."

Second Quarter and First Half 2024 Financial Results, Corporate Guidance, and Updates

Product Revenue and Guidance

2Q24 Total Product Revenue: $31.1 million for the second quarter ended June 30, 2024, following the initial launch of Amtagvi on February 20, 2024.
Amtagvi Revenue: 2Q24 represents the first quarter of Amtagvi sales in the U.S. with product revenue of $12.8 million, which is only recognized upon patient infusion.
Proleukin Revenue: 2Q24 product revenue also includes $18.3 million in sales for Proleukin, which is used in the Amtagvi treatment regimen and in global commercial and clinical uses in other settings. Proleukin revenue is recognized upon delivery to distributors and ATCs and purchased several months in advance of anticipated infusions and revenue recognition for Amtagvi use.
FY24 and FY25 Total Product Revenue Guidance: Iovance expects significant quarter-over-quarter growth in product revenue to continue throughout 2024, 2025, and beyond as the adoption curve for Amtagvi steepens. More than 55 patients have been infused with Amtagvi since the first commercial infusion in April 2024, which includes 25 patients infused in the second quarter and over 30 patients infused since the start of the third quarter.
Revenue Guidance in 3Q24: With utilization broadening and the rate of infusions substantially increasing, total infusions during the third quarter have markedly exceeded infusions in the second quarter. Total product revenue in the third quarter of 2024 is expected to be within the range of $53 to $55 million.
Revenue Guidance in FY24: Total product revenue for the full year 2024 is anticipated to be within the range of $160 to $165 million, reflecting three quarters of Amtagvi sales following FDA approval in mid-February. Additionally, demand for Proleukin remains strong and continues to be a leading indicator of Amtagvi sales.
Revenue Guidance in FY25: Robust growth for Amtagvi continues as existing ATC demand increases and new ATCs are onboarded. As such, total product revenue for 2025 is anticipated to be within the range of $450 to $475 million, the first full calendar year of Amtagvi sales, with gross margins expected to increase to greater than 70% over the next several years. In line with Amtagvi demand, Proleukin revenue is expected to significantly increase in 2025.
Cash Position: As of July 24, 2024, Iovance had cash, cash equivalents, investments, and restricted cash of $449.6 million, compared to $346.3 million at December 31, 2023. The current cash position and anticipated product revenue are expected to be sufficient to fund current and planned operations, including manufacturing expansion, into early 2026.
Amtagvi (Lifileucel) U.S. Launch Highlights in Advanced Melanoma

The U.S. FDA approved Amtagvi (lifileucel) on February 16, 2024, as the first treatment option for advanced melanoma after anti-PD-1 and targeted therapy. Amtagvi is also the first FDA-approved T cell therapy for a solid tumor indication.
Onboarding is complete at more than 50 U.S. ATCs across 29 states and more than 90% of addressable patients are now located within 200 miles of an ATC. More than 70 ATCs remain on track to be onboarded by the end of 2024.
Manufacturing turnaround time has been on-target with initial launch expectations of approximately 34 days from inbound to return shipment to ATCs, with efforts underway to reduce the turnaround time in the near term. The commercial manufacturing experience is consistent with prior clinical experience.
Amtagvi is a preferred second-line or subsequent therapy in the National Comprehensive Cancer Network guidelines for treatment of cutaneous melanoma.
Reimbursement remains successful, with an average financial clearance time of about three weeks.
Approximately 75% of enrolled Amtagvi patients are covered by private payers. To date, payers covering more than 225 million lives have already added Amtagvi to policies during the first five months of launch.
Lifileucel Launch Expansion into New Markets and Indications

Amtagvi has the potential to address more than 20,000 patients annually with previously treated advanced melanoma across the U.S. and multiple global markets where regulatory dossiers have been submitted or are planned in 2024 and 2025.1
A marketing authorization application was submitted to the European Medicines Agency for lifileucel for the treatment of adult patients with unresectable or metastatic melanoma previously treated with a PD-1 blocking antibody, and if BRAF V600 mutation positive, a BRAF inhibitor with or without a MEK inhibitor. If approved, lifileucel will be the first and only approved therapy in this treatment setting in all European Union member states.
Regulatory dossiers remain on track for submission in the following markets with significant populations of previously treated advanced melanoma patients:
UK and Canada in the second half of 2024
Australia in the first half of 2025
Additional countries, including Switzerland, in the second half of 2025 and early 2026
Iovance TIL Cell Therapy Pipeline Highlights

Lifileucel in Frontline Advanced Melanoma
Updated clinical data from Cohort 1A of the IOV-COM-202 trial was presented at ASCO (Free ASCO Whitepaper) 2024 and demonstrated an unprecedented rate, depth and durability of responses, including a 30% confirmed complete response rate, and a differentiated safety profile in advanced melanoma patients who were naive to immune checkpoint inhibitors. These results further support the rationale for the registrational Phase 3 TILVANCE-301 trial and the global opportunity for lifileucel in combination with pembrolizumab as a frontline therapy for advanced melanoma.
A new cohort, 1D, will begin in the IOV-COM-202 trial in solid tumors to investigate lifileucel in combination with nivolumab and relatlimab in patients with frontline advanced melanoma, representing another potential best-in-class frontline alternative for physicians and patients in the U.S.
Strong momentum continues with global site activation and patient enrollment in the TILVANCE-301 trial, with more than 40 active sites across 10 countries including the U.S., Europe, Australia, and Canada, and an additional 60 sites across 18 countries committed to join the trial. TILVANCE-301 is intended to support accelerated and full U.S. approvals of Amtagvi in combination with pembrolizumab in frontline advanced melanoma, as well as full approval of Amtagvi in post-anti-PD-1 melanoma.
Lifileucel in Non-Small Cell Lung Cancer (NSCLC)
Enrollment is accelerating in the IOV-LUN-202 registrational Phase 2 trial in post-anti-PD-1 NSCLC with high demand at clinical sites in the U.S., Canada, and Europe. Iovance is also activating sites in additional regions with strong track records for enrollment in NSCLC studies.
The FDA previously provided positive regulatory feedback on the proposed potency matrix for lifileucel in NSCLC, as well as the single-arm IOV-LUN-202 trial design to support accelerated approval of lifileucel in post-anti-PD-1 NSCLC.
Iovance expects to complete enrollment and report topline data from the registrational cohorts in IOV-LUN-202 in 2025 to support a potential supplemental biologics license application for lifileucel in 2026 for potential accelerated approval.
Lifileucel in Endometrial Cancer
The IOV-END-201 Phase 2 trial was initiated in the second quarter of 2024 to investigate lifileucel for advanced endometrial cancer patients who have progressed after platinum-based chemotherapy and anti-PD-1 therapy regardless of mismatch repair (MMR) status. IOV-END-201 is supported by positive feedback from gynecological oncology experts as well as preclinical and manufacturing success data to be presented at a conference in 2024.
Endometrial cancer represents a significant opportunity for TIL cell therapy to address an additional unmet medical need in the post-anti-PD-1 treatment setting and may address both MMR deficient and proficient tumors. There are no currently approved therapies in the emerging second-line setting after frontline post-anti-PD1 therapy and chemotherapy.

Next Generation TIL Pipeline
IOV-4001 (PD-1 Inactivated TIL Cell Therapy): The Phase 1 safety portion concluded in the first in human IOV-GM1-201 trial to investigate PD-1 inactivated TIL cell therapy (IOV-4001) in previously treated advanced melanoma and NSCLC, and the trial is progressing successfully into the multi-center Phase 2 efficacy stage. Iovance continues to utilize the TALEN technology licensed from Cellectis to develop other investigational gene-edited TIL cell therapies with multiple knockout targets to potentially improve efficacy.
Next Generation IL-2 for TIL Treatment Regimen: Iovance plans to submit an Investigational New Drug application (IND) for a Phase 1/2 clinical trial of IOV-3001, a second-generation, modified interleukin-2 (IL-2) analog, for use in the TIL therapy treatment regimen in the third quarter of 2024. Results from non-human primate and IND-enabling studies of IOV-3001 were presented at ASCO (Free ASCO Whitepaper) 2024 and demonstrated the potential for improved safety with strong effector T cell expansion.
Next Generation, Cytokine-Tethered TIL Therapy: A genetically engineered, inducible, and tethered IL-12 TIL cell therapy, designated IOV-5001, is in IND-enabling studies. In preclinical studies, IOV-5001 augmented anti-tumor activity in vitro, and a clinical trial of a prior generation IL-12 TIL therapy at the National Cancer Institute showed improved efficacy. An IND submission is planned in 2025.
Manufacturing Capacity Expansion

The Iovance Cell Therapy Center (iCTC), and an FDA-approved contract manufacturer, currently have capacity to treat several thousands of patients annually. Expansion is currently underway for the iCTC campus to supply TIL cell therapies for more than 5,000 patients annually in the next few years. The long-term goal is to establish a manufacturing network to address more than 10,000 patients annually.
Corporate Updates

Iovance currently owns more than 210 granted or allowed U.S. and international patents and patent rights for Amtagvi and other TIL-related technologies that are expected to provide Amtagvi with exclusivity through at least 2042. This patent portfolio covers TIL compositions and methods of treatment and manufacturing in a broad range of cancers, with Gen 2 patent rights expected to provide exclusivity for Amtagvi into 2038 and additional patent rights, including methods of treating melanoma and compositions and methods for potency assays, expected to provide exclusivity into 2040 and 2042, respectively. Iovance also owns an industry-leading patent portfolio covering TIL products produced with genetic engineering, using core biopsies and peripheral blood as starting material, and using combinations of TIL products with checkpoint inhibitors, as well as Iovance’s proprietary IovanceCares system. More information on Iovance’s patent portfolio is available on the Intellectual Property page on www.iovance.com.
Iovance recently renewed its Cooperative Research and Development Agreement (CRADA) with the National Cancer Institute (NCI). Over the five-year term of the CRADA, Iovance and NCI teams will collaborate closely on preclinical and clinical development of enhanced tumor reactive TIL products for the treatment of a broad range of common epithelial cancers. Iovance retains an option to negotiate an exclusive license to inventions developed under the CRADA.
Second Quarter and First Half 2024 Financial Results

As of July 24, 2024, Iovance’s unaudited cash position is approximately $449.6 million, which includes net proceeds of approximately $200.0 million raised from an at-the market (ATM) equity financing facility during the second and third quarter of 2024. The current cash position and anticipated product revenue are expected to be sufficient to fund current and planned operations into early 2026. Iovance had $346.3 million in cash, cash equivalents, investments, and restricted cash at December 31, 2023.

Net loss for the second quarter of 2024 was $97.1 million, or $0.34 per share, compared to a net loss of $106.5 million, or $0.47 per share, for the second quarter ended June 30, 2023. Net loss for the first half of 2024 was $210.1 million, or $0.76 per share, compared to a net loss of $213.9 million, or $0.98 per share, for the six-month period ended June 30, 2023.

Revenue was $31.1 million for the second quarter of 2024 and consisted of product revenue from the initial quarter of Amtagvi sales as well as recurring revenue from Proleukin. Iovance recognized $12.8 million in revenue from Amtagvi infusions that were completed during the second quarter of 2024 and $18.3 million in global revenue for Proleukin.

Revenue for the first half of 2024 was $31.8 million and reflected product revenue from Proleukin and Amtagvi. Revenue for the first half of 2023 was $0.2 million for global sales of Proleukin, which Iovance began to recognize during the three-month period ended June 30, 2023.

The increases in revenue in the second quarter and first half of 2024 over the prior year periods were primarily attributable to the U.S. launch of Amtagvi, including revenue recognized for Amtagvi, as well as significant growth in U.S. Proleukin revenue for use in the Amtagvi treatment regimen, beginning in the second quarter of 2024.

Cost of sales for the three and six months ended June 30, 2024 was $31.4 million and $38.6 million, respectively, primarily related to costs associated with sales of Amtagvi and Proleukin, certain costs associated with patient drop off and manufacturing success rates, non-cash amortization expense for intangible assets, and royalties payable on product sales. Cost of sales for both the three and six months ended June 30, 2023 was $2.1 million, primarily related to non-cash amortization for intangible assets.

The increases in cost of sales in the second quarter and first half of 2024 over the prior year periods were primarily attributable to the initiation of commercial manufacturing and related costs for the U.S. launch of Amtagvi during the first half of 2024.

Research and development expenses were $62.1 million for the second quarter of 2024, a decrease of $24.2 million compared to $86.3 million for the same period ended June 30, 2023. Research and development expenses were $141.9 million for the first half of 2024, a decrease of $27.2 million compared to $169.1 million for the same period ended June 30, 2023.

The decreases in research and development expenses in the second quarter and first half of 2024 over the prior year periods were primarily attributable to the transition of Amtagvi to commercial manufacturing, decreased costs associated with certain clinical activities in the first half of 2024, and the completion of pre-commercial qualification activities in 2023. These decreases in research and development were partially offset by increases in stock-based compensation resulting from growth in headcount.

Selling, general and administrative expenses were $39.6 million for the second quarter of June 2024, an increase of $17.7 million compared to $21.9 million for the same period ended June 30, 2023. Selling, general and administrative expenses were $71.0 million for the first half of 2024, an increase of $21.0 million compared to $50.0 million for the same six-month period ended June 30, 2023.

The increase in selling, general and administrative expenses in the second quarter and first half of 2024 compared to the prior year periods was primarily attributable to increases in headcount and related costs, including stock-based compensation, to support the growth in the overall business and related corporate infrastructure, as well as legal costs and costs incurred to support the commercialization of Amtagvi and Proleukin.

For additional information, please see the Company’s Selected Condensed Consolidated Balance Sheets and Statements of Operations below.

Webcast and Conference Call

Management will host a conference call and live audio webcast to discuss these results and provide a corporate update today at 4:30 p.m. ET. To listen to the live or archived audio webcast, please register at View Source The live and archived webcast can be accessed in the Investors section of the Company’s website, IR.Iovance.com, for one year.

1. World Health Organization International Agency for Research on Cancer (IARC) GLOBOCAN 2022.

On August 8, 2024 Intensity Therapeutics, Inc. ("Intensity" or "the Company") (Nasdaq: INTS), a late-stage clinical biotechnology company focused on the discovery and development of proprietary, novel immune-based intratumoral cancer therapies designed to kill tumors and increase immune system recognition of cancers, reported second quarter 2024 financial results and provides a corporate update (Press release, Intensity Therapeutics, AUG 8, 2024, View Source [SID1234645608]).

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Corporate Update

•In July 2024, the Company initiated and dosed its first patient in a Phase 3 open-label, randomized study (the "INVINCIBLE-3 Study") testing INT230-6, Intensity’s lead drug candidate, as a monotherapy compared to the standard of care ("SOC") drugs in second- and third-line treatment for certain soft tissue sarcoma subtypes. The Company plans to enroll 333 patients with an endpoint of overall survival and has screened and qualified over 50 sites for the INVINCIBLE-3 Study. Contract negotiations are in process to approve and activate these sites, which is estimated to take up to six months per site.

•In May 2024, the Company executed a collaboration agreement with SAKK to conduct a Phase 2 randomized, controlled study (the "INVINCIBLE-4 Study") evaluating clinical and biological effects of INT230-6 followed by SOC vs. SOC alone in early-stage triple-negative breast cancer. The Company plans to enroll 54 to 60 patients in Europe. The INVINCIBLE-4 Study endpoint is the change in the pathological complete response rate for the combination compared to the SOC alone. The Company expects that the data from INVINCIBLE-4 Study will provide data to size a follow-on Phase 3 study. The Company is in the process of screening and qualifying sites for the INVINCIBLE-4 Study, and plans to initiate the study in the third quarter of 2024.

•In May 2024, the Company appointed Thomas Dubin, J.D., MPH, to the Intensity board of directors, increasing the size of the board to five members. Mr. Dubin has extensive pharmaceutical business development, regulatory, and commercialization experience.

"The dosing of the first patient in our randomized controlled Phase 3 sarcoma trial is the most important development milestone Intensity has reached to date," said Lewis H. Bender, Intensity Founder, President and CEO. "A journey of 1,000 miles starts with the first step, and a successful clinical study outcome can only be achieved by initiating sites and enrolling patients. For our Phase 3 study, we have qualified over 50 sites and are in contract and budget negotiations to initiate treatment in multiple countries. Also, our collaboration with SAKK has progressed well during this quarter, and we are also looking forward to enrolling the first patient in the INVINCIBLE-4 study. Finally, I am excited that Tom Dubin joined our Board. Tom is a highly successful and sophisticated biotech executive who has already provided key insights."

Second Quarter 2024 Financial Results

Research and development expenses were $3.6 million for the three months ended June 30, 2024, compared to $0.9 million for the same period in 2023. The increase was primarily due to preliminary work related to the INVINCIBLE-3 Study, and to a lesser extent, costs for manufacturing a new batch of INT230-6 and increased expenses related to salary, benefits, and stock-based compensation.

General and administrative expenses were $1.5 million for the three months ended June 30, 2024, compared to $0.4 million for the same period in 2023. The increase was primarily due to increased expenses related to salary, benefits and stock-based compensation, higher legal, audit, and consulting fees, and higher directors and officers insurance.

Upon the Company’s initial public offering in June 2023, convertible notes outstanding converted to common stock, resulting in a $2.3 million loss on debt conversion. In addition, a preferred stock deemed dividend of $1.3 million was also recognized in June 2023, representing the value that was transferred to Series B and C preferred stockholders upon triggering of anti-dilution provisions concurrent with the initial public offering.

Overall, net loss was $5.0 million for the three months ended June 30, 2024, compared to a net loss of $3.7 million for the three months ended June 30, 2023.

As of June 30, 2024, cash, cash equivalents and marketable debt securities totaled $6.3 million, which the Company expects will be sufficient to fund operations into the first quarter in 2025.

About INT230-6
INT230-6, Intensity’s lead proprietary investigational product candidate, is designed for direct intratumoral injection. INT230-6 was discovered using Intensity’s proprietary DfuseRx℠ technology platform. The drug is comprised of two proven, potent anti-cancer agents, cisplatin and vinblastine, and a penetration enhancer molecule (SHAO) that helps disperse potent cytotoxic drugs throughout tumors for diffusion into cancer cells. These agents remain in the tumor, resulting in a favorable safety profile. In addition to local disease control and direct tumor killing, INT230-6 causes a release of a bolus of neoantigens specific to the malignancy, leading to immune system engagement and systemic anti-tumor effects. Importantly, these effects are mediated without immunosuppression which often occurs with systemic chemotherapy.

On August 8, 2024 Intellia Therapeutics, Inc. (NASDAQ:NTLA), a leading clinical-stage gene editing company focused on revolutionizing medicine with CRISPR-based therapies, reported operational highlights and financial results for the second quarter ended June 30, 2024 (Press release, Intellia, AUG 8, 2024, View Source [SID1234645607]).

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"We are delighted to report the Phase 2 study of NTLA-2002 met its primary efficacy and all secondary endpoints at both dose levels and, importantly, provided clear support for advancing the 50 mg dose into the pivotal Phase 3 trial in patients with hereditary angioedema," said Intellia President and Chief Executive Officer John Leonard, M.D. "Based on these positive results and our recent successful end-of-Phase 2 meeting with the FDA, we see a clear path to initiating the Phase 3 trial in the coming months. We look forward to presenting the detailed Phase 2 results at a medical meeting in the fourth quarter as we continue to advance what we believe could be a functional cure for hereditary angioedema. With three pivotal Phase 3 trials and our first gene insertion trial expected to be active by year-end, Intellia is closer than ever to transforming the future of medicine with our one-time, in vivo gene editing therapies."

Second Quarter 2024 and Recent Operational Highlights

Hereditary Angioedema (HAE)

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NTLA-2002: NTLA-2002 is a wholly owned, investigational in vivo CRISPR-based therapy designed to knock out the KLKB1 gene in the liver, with the goal of lifelong control of HAE attacks after a single dose.
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Intellia announced today positive topline results from the Phase 2, randomized, double-blind, placebo-controlled study of NTLA-2002 in patients with HAE. The clinical trial met its primary efficacy and all secondary endpoints in the 16-week primary observation period, with a single 25 mg or 50 mg dose leading to deep reductions in attacks. No new safety findings were observed. Intellia has selected the 50 mg dose for further evaluation in the global pivotal Phase 3 trial based upon the greater number of patients with complete attack elimination and greater kallikrein protein reduction compared to the 25 mg dose observed in the Phase 2 study, which is consistent with the previously reported Phase 1 results. The Company plans to present the detailed Phase 2 data at an upcoming medical meeting in the fourth quarter of this year.
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The Company announced today the successful completion of an end-of-Phase 2 meeting with the U.S. Food and Drug Administration (FDA) supporting its Phase 3 plans for NTLA-2002. The Phase 3 study is on track to initiate in the second half of 2024, subject to regulatory feedback.
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In June, Intellia presented positive long-term data from the ongoing Phase 1 study. Eight of 10 patients remained completely attack-free following the 16-week primary observation period. These patients have experienced ongoing attack-free durations of greater than 18 months after a single-dose treatment, with the longest ongoing individual attack-free duration reaching over 26 months. Across all patients, NTLA-2002 led to a 98% mean reduction in monthly HAE attack rate. Consistent with previously reported results, NTLA-2002 was well-tolerated, with the majority of adverse events being mild in severity through the latest follow-up. These interim data were presented at the European Academy of Allergy and Clinical Immunology (EAACI) Congress 2024 in Valencia, Spain.
Transthyretin (ATTR) Amyloidosis

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NTLA-2001: NTLA-2001, now known as nexiguran ziclumeran (nex-z), is an investigational in vivo CRISPR-based therapy designed to inactivate the TTR gene in liver cells, thereby preventing the production of transthyretin (TTR) protein for the treatment of ATTR amyloidosis. NTLA-2001 offers the possibility of halting and reversing the disease by driving a deep, consistent and potentially lifelong reduction in TTR protein after a single dose. Intellia leads development and commercialization of NTLA-2001 in collaboration with Regeneron.

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ATTR Amyloidosis with Cardiomyopathy (ATTR-CM):
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The pivotal Phase 3 MAGNITUDE trial is enrolling rapidly and continues to track ahead of the Company’s initial projections. During the second quarter, the Company received approval for its application under the new European Union Clinical Trials Regulation, which enables the Phase 3 trial to proceed in Denmark, Germany, France, Italy, Spain and Sweden. The MAGNITUDE trial of NTLA-2001 is now cleared by regulatory agencies in over 12 countries and actively enrolling at over 35 sites globally.
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Hereditary ATTR Amyloidosis with Polyneuropathy (ATTRv-PN):
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The Company plans to initiate a pivotal Phase 3 trial of NTLA-2001 as a single-dose treatment for ATTRv-PN by year-end. As previously announced, the study is expected to be a small, placebo-controlled trial conducted at ex-U.S. sites with approximately 50 ATTRv-PN patients.
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Intellia plans to present updated data from the ongoing Phase 1 study in the second half of 2024.
Alpha-1 Antitrypsin Deficiency (AATD)-Associated Lung Disease

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NTLA-3001: NTLA-3001 is a first-in-class CRISPR-mediated in vivo targeted gene insertion development candidate for the treatment of AATD-associated lung disease. It is designed to precisely insert the wild-type SERPINA1 gene, which encodes the alpha-1 antitrypsin (AAT) protein, with the potential to restore permanent expression of fully functional AAT protein to normal levels after a single dose. This is Intellia’s first wholly owned gene insertion program.
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In July, Intellia announced the authorization of its Clinical Trial Application by the United Kingdom’s Medicines and Healthcare products Regulatory Agency (MHRA) to initiate a first-in-human study of NTLA-3001. Intellia expects to dose the first patient in the Phase 1/2 study of NTLA-3001 in the second half of 2024.
In Vivo Platform Expansion

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In June, Intellia presented positive clinical proof-of-concept data that redosing with CRISPR, utilizing the Company’s proprietary non-viral, LNP-based delivery platform, enabled an additive pharmacodynamic effect. In the three patients who previously received the lowest dose of 0.1 mg/kg in the Phase 1 dose-escalation study of NTLA-2001, follow-on dosing with a 55 mg dose of NTLA-2001 led to a deeper protein reduction. Median reduction in serum TTR was 90% at day 28 after redosing. The corresponding reduction from original baseline levels was a 95% median reduction in serum TTR. NTLA-2001 was generally well tolerated across all patients after receiving the follow-on dose. While redosing is not planned for the NTLA-2001 program in ATTR amyloidosis, a redosing option could bean important advantage of Intellia’s LNP-based delivery platform for future investigational therapies where a target additive effect is desired. These data were presented at the Peripheral Nerve Society (PNS) Annual Meeting in Montreal, Canada.
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Intellia is expanding the range of diseases that can be targeted with its CRISPR-based technologies by deploying new editing and delivery innovations. This includes advancing gene editing programs in five different tissues outside the liver, either independently or in collaboration with partners. These research and preclinical programs are targeting diseases that originate in the bone marrow, brain, muscle, lung and eye, which, if successful, could dramatically expand the opportunities for CRISPR-based treatments.
Ex Vivo Program Updates

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Intellia is advancing multiple programs, wholly owned and in collaboration with partners, utilizing its allogeneic platform for the treatment of immuno-oncology and autoimmune diseases. The Company’s proprietary allogeneic cell engineering platform avoids both T cell- and NK cell-mediated rejection in preclinical models, a key unsolved challenge with other investigational allogeneic approaches. Cell therapies engineered with Intellia’s allogeneic platform, combined with edits to enhance cell function, offer a new approach to target both hematological and solid tumors.
Corporate Updates

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In June, Intellia announced the appointment of Brian Goff to its board of directors. Mr. Goff joins the board of directors with over three decades of commercialization, operations and sales and marketing experience at leading biopharmaceutical companies.
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In June, Intellia announced the appointment of Edward Dulac as Executive Vice President, Chief Financial Officer, and Treasurer, effective July 22, 2024. Mr. Dulac succeeds Glenn Goddard, who stepped down from his role effective June 30, 2024. Mr. Dulac joins Intellia with more than 20 years of combined finance, business development and corporate strategy experience.
Upcoming Events

The Company will participate in the following events during the third quarter of 2024:

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Morgan Stanley 22nd Annual Global Healthcare Conference, September 4, New York
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Wells Fargo Healthcare Conference, September 4, Boston
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Cantor Global Healthcare Conference, September 17, New York

Second Quarter 2024 Financial Results

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Cash Position: Cash, cash equivalents and marketable securities were $939.9 million as of June 30, 2024, compared to $1.0 billion as of December 31, 2023. The decrease was driven by cash used to fund operations of $234.4 million. The Company’s investments were offset in part by $96.4 million of net equity proceeds from the Company’s "At the Market" (ATM) program, $35.9 million of reimbursement from collaborators, including a one-time $30.0 million payment received in April 2024 related to the Company’s technology collaboration with Regeneron, $25.1 million of interest income and $4.8 million in proceeds from employee-based stock plans. The cash position is expected to fund operations into late 2026.
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Collaboration Revenue: Collaboration revenue was $7.0 million during the second quarter of 2024, compared to $13.6 million during the second quarter of 2023. The $6.6 million decrease was mainly driven by a reduction in revenue related to the AvenCell license and collaboration agreement.
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R&D Expenses: Research and development (R&D) expenses were $114.2 million during the second quarter of 2024, compared to $115.3 million during the second quarter of 2023. The $1.1 million decrease was primarily driven by a decrease in employee-related expenses. Stock-based compensation expense included in R&D expenses was $25.4 million for the second quarter of 2024.
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G&A Expenses: General and administrative (G&A) expenses were $31.8 million during the second quarter of 2024, compared to $30.7 million during the second quarter of 2023. The $1.1 million increase was primarily related to stock-based compensation. Stock-based compensation expense included in G&A expenses was $15.4 million for the second quarter of 2024.
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Net Loss: Net loss was $147.0 million for the second quarter of 2024, compared to $123.7 million during the second quarter of 2023.
Conference Call to Discuss Second Quarter 2024 Results

The Company will discuss these results on a conference call today, Thursday, August 8 at 8 a.m. ET.

To join the call:

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U.S. callers should dial 1-833-316-0545 and international callers should dial 1-412-317-5726 approximately five minutes before the call. All participants should ask to be connected to the Intellia Therapeutics conference call.
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Please visit this link for a simultaneous live webcast of the call.
A replay of the call will be available through the Events and Presentations page of the Investors & Media section on Intellia’s website at intelliatx.com, beginning on August 8 at 12 p.m. ET.