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 Sanofi reported new results from the two-part, double-randomized, German-speaking Myeloma Multicenter Group (GMMG)-HD7 phase 3 study show that Sarclisa (isatuximab) in combination with lenalidomide, bortezomib, and dexamethasone (RVd) during induction therapy in transplant-eligible, newly diagnosed multiple myeloma (NDMM) significantly prolonged progression-free survival (PFS) from first randomization, resulting in a statistically significant and clinically meaningful reduction in disease progression or death, compared to RVd induction regardless of the maintenance regimen (Press release, Sanofi, AUG 8, 2024, View Source [SID1234645624]). Full results will be submitted for presentation at a forthcoming medical meeting.

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Hartmut Goldschmidt, MD
President of GMMG, Professor of Medicine at the Heidelberg University Hospital (UKHD), Germany and principal investigator of the study
"Successful induction therapy is one of the most critical components to reduce the relapse or recurrence risk in patients with newly diagnosed multiple myeloma. While we observed this investigational combination showed improved minimal residual disease negativity rates in the bone marrow, indicating potentially deeper responses after induction, further follow-up was needed to better understand how this translated to long-term outcomes. These data provide evidence that the Isa-RVd regimen potentially improves progression-free survival in the frontline, transplant-eligible population and supports the potential of this quadruplet to become a new standard-of-care induction regimen in this treatment setting."

GMMG-HD7 is one of six phase 3 studies to report positive results for Sarclisa in patients with multiple myeloma, which includes four positive readouts of a Sarclisa-based quadruplet in the frontline setting. The most recent included results from the IMROZ phase 3 study evaluating the investigational use of Sarclisa with VRd versus VRd for patients with transplant-ineligible NDMM, demonstrating a statistically significant and clinically meaningful improvement in PFS and a higher proportion of patients with minimal residual disease (MRD) negativity.

Dietmar Berger, MD, PhD
Chief Medical Officer and Global Head of Development at Sanofi
"The GMMG-HD7 study was designed to better understand the distinct effect of targeting CD38 with Sarclisa in induction versus maintenance treatment of transplant-eligible patients. These data build upon our belief that Sarclisa has the potential to be a best-in-class CD38 therapy that could improve long-term outcomes versus the standard-of-care for certain patients. We look forward to the full data presentation and continuing our mission of helping make a meaningful difference for people living with multiple myeloma."

In December 2021, Sanofi and GMMG shared the results from part one, which met the primary endpoint of MRD negativity after induction therapy and before transplant in NDMM patients. The GMMG-initiated study is being conducted in close collaboration with Sanofi based on jointly defined research. Sanofi provided financial support to GMMG for this study. The use of Sarclisa in combination with RVd is investigational and has not been evaluated by any regulatory authority.

While considered a rare disease, MM is the second most common hematologic malignancy,1 with more than 180,000 new diagnoses of MM worldwide yearly.2 Despite available treatments, MM remains an incurable malignancy in most patients with an estimated 61% five-year survival rate for newly diagnosed patients.3 Since MM does not have a cure, most patients will relapse. Relapsed MM is the term for when the cancer returns after treatment or a period of remission. Refractory MM refers to when the cancer does not respond or no longer responds to therapy.

About the GMMG-HD7 study
GMMG-HD7 is a pivotal randomized, open-label, multicenter, 2-part phase 3 study evaluating Sarclisa in combination with RVd versus RVd induction followed by post-transplant re-randomization to Sarclisa plus lenalidomide versus lenalidomide maintenance in transplant-eligible NDMM patients. The study enrolled 662 patients with transplant-eligible NDMM across 67 sites in Germany. In the first part of the study, all participants were equally randomized to receive three 42-day cycles of RVd in both arms of the study, while Sarclisa was added to only one study arm. In the second part of the study, patients were re-randomized post-transplant to receive Sarclisa plus lenalidomide or lenalidomide alone as maintenance therapy. During the study, Sarclisa was administered through an intravenous infusion at a dose of 10 mg/kg once weekly for the first four weeks of cycle one, then every other week for the rest of the induction period.

MRD negativity was assessed by next-generation flow cytometry (sensitivity of 1×10-5) after induction. In the latest readout of the study, PFS for both Sarclisa plus RVd as an induction therapy, regardless of maintenance treatment, and Sarclisa plus lenalidomide as a maintenance regimen were measured from first randomization.

GMMG-HD7 protocol defined the primary endpoints of MRD negativity after induction treatment for the first part of the study, and PFS following the second randomization after transplant for part two of the study, in which Sarclisa was added to lenalidomide maintenance, with the latter primary endpoint anticipated to be available at a later date. The key secondary endpoint for the first part of the study was PFS from first randomization. Additional secondary endpoints included rates of complete response after induction, and intensification, overall survival, and safety.

About Sarclisa
Sarclisa (isatuximab) is a monoclonal antibody that binds to a specific epitope on the CD38 receptor on MM cells, inducing distinct antitumor activity. It is designed to work through multiple mechanisms of action including programmed tumor cell death (apoptosis) and immunomodulatory activity. CD38 is highly and uniformly expressed on the surface of MM cells, making it a target for antibody-based therapeutics such as Sarclisa.

Based on the ICARIA-MM phase 3 study, Sarclisa is approved in more than 50 countries, including the US and the EU, in combination with pomalidomide and dexamethasone for the treatment of patients with relapsed refractory MM (RRMM) who have received ≥2 prior therapies, including lenalidomide and a proteasome inhibitor and who progressed on last therapy. Based on the IKEMA phase 3 study, Sarclisa is also approved in 50 countries in combination with carfilzomib and dexamethasone, including in the US for the treatment of patients with RRMM who have received 1–3 prior lines of therapy and in the EU for patients with MM who have received at least one prior therapy. In the US, the non-proprietary name for Sarclisa is isatuximab-irfc, with irfc as the suffix designated in accordance with nonproprietary naming of biological products guidance for industry issued by the US Food and Drug Administration.

Sarclisa continues to be evaluated in multiple ongoing phase 3 clinical studies in combination with current standard treatments across the MM treatment continuum. It is also under investigation for the treatment of other hematologic malignancies, and its safety and efficacy have not been evaluated by any regulatory authority outside of its approved indication.

Sanofi is committed to pursuing the advancement of Sarclisa through several investigational studies across the MM treatment continuum. Various patient-centric clinical development programs aim to bring Sarclisa to more patients, intercept the disease earlier in the treatment journey, and explore potential new combinations including assessing subcutaneous administration via a proprietary on body device system. The safety and efficacy of Sarclisa has not been evaluated by any regulatory authority outside of its approved indications and methods of delivery.

In striving to become the number one immunoscience company globally, there is a commitment to advancing oncology innovation. The pipeline is being reshaped and prioritized, leveraging expertise in immunoscience to drive progress. Efforts are centered on select hematologic malignancies and solid tumors with critical unmet needs, including multiple myeloma, acute myeloid leukemia, certain types of lymphomas, as well as gastrointestinal and lung cancers.

For more information on Sarclisa clinical studies, please visit www.clinicaltrials.gov.

About the German-speaking Myeloma Multicenter Group (GMMG)
GMMG is the largest study group focusing on MM in Germany, with headquarters based in Heidelberg. Within the last 20+ years, the GMMG study group has performed numerous studies including five randomized, multicenter phase 3 studies with 4,000 patients enrolled from about 90 participating and co-treating centers throughout Germany. The overall goal of GMMG is to generate improved therapies for myeloma patients through the development and testing of novel and personalized, genome- and signaling-driven treatment strategies. The GMMG has set itself the goal of achieving further approvals for effective antibody-based drug combinations for the first-line treatment of myeloma patients, in which antibody-based treatment regimens have been integrated into seven GMMG study concepts (CONCEPT, DANTE, DADA, HD6, HD7, HD8, HD9 and HD10).

On August 8, 2024 Crinetics Pharmaceuticals, Inc. (Nasdaq: CRNX), a clinical stage pharmaceutical company focused on the discovery, development and commercialization of novel therapeutics for endocrine diseases and endocrine-related tumors, reported financial results for the second quarter ended June 30, 2024 (Press release, Crinetics Pharmaceuticals, AUG 8, 2024, View Source [SID1234645592]).

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"The second quarter of 2024 has been yet another successful period of executing our strategy to become the world’s premier endocrine company," said Scott Struthers, Ph.D., Founder and Chief Executive Officer of Crinetics. "Our strong presence at the ENDO 2024 meeting in June showcased the breadth and depth of our pipeline. Our second internally-developed candidate atumelnant* showed profoundly positive initial results in the treatment of both congenital adrenal hyperplasia and Cushing’s disease. We anticipate reporting additional data in both indications later in 2024. Data presentations from the paltusotine program continue to demonstrate clinical benefits for patients, providing even more compelling support for its potential to treat people with acromegaly. We remain on track for our planned paltusotine NDA filing in acromegaly later this year, and multiple workstreams are underway in anticipation of an expected market launch in 2025."

Crinetics today also announced that Marc Wilson will be transitioning from his role as Chief Financial Officer for personal reasons and the Company has initiated a search for a successor. Mr. Wilson will continue to serve at full capacity until a successor is named and will provide all necessary support to ensure a seamless transition.

"Marc has been an invaluable member of the Crinetics team over the last six years and we thank him for his outstanding contributions," said Scott Struthers, Ph.D., Founder and Chief Executive Officer of Crinetics. "His leadership has been instrumental in the success of our capital markets activities, the build-out of our finance and corporate affairs functions, and the maturation of our organization and culture. During his tenure, we have successfully raised a significant amount of capital to fund development of our differentiated pipeline, our rapidly growing clinical and research programs, and our anticipated commercial launch."

"I am proud of what Crinetics has accomplished, and it has been a privilege to work with such a talented and dedicated team over the last six years," said Mr. Wilson. "The company is in a strong financial position to invest across its deep pipeline, and I have unwavering confidence in the team’s ability to continue discovering new, meaningful therapies and advance them through the clinic to reach as many patients as possible. I will continue to support the company through this transition and look forward to following the company’s continued success."

Second Quarter 2024 and Recent Highlights:
Presented positive initial results from atumelnant studies at the Endocrine Society’s Annual Meeting (ENDO 2024). In June, Crinetics presented positive initial results from its ongoing, open-label studies of atumelnant for the treatment of ACTH-dependent Cushing’s syndrome and congenital adrenal hyperplasia (CAH) at ENDO 2024 in Boston.
Presented data from paltusotine development program at ENDO 2024. In June, Crinetics presented findings from its paltusotine development program in acromegaly. Data presented included results of the Phase 3 PATHFNDR-2 trial, a new analysis of patient reported outcome data from the Phase 3 PATHFNDR-1 trial, and interim long-term efficacy and safety results at 42 months from the open-label ACROBAT Advance extension study.
Selected development candidates in two programs. Crinetics has identified an oral parathyroid hormone antagonist development candidate for the treatment of hyperparathyroidism and IND-enabling studies have commenced. In addition, a development candidate in the SST3 agonist program was selected for the treatment of autosomal dominant polycystic kidney disease.
Scott Struthers, Ph.D., founder and chief executive officer of Crinetics, was named an Entrepreneur of The Year 2024 Pacific Southwest Award winner.
Strengthened scientific leadership team. In April, Crinetics appointed Lise Kjems, M.D., Ph.D. as Senior Vice President of Endocrinology Clinical Research, and in May, Crinetics appointed Robert M. Cuddihy, M.D., as Senior Vice President of Medical Affairs.
Key Upcoming Milestones
Topline data and additional data from the ongoing Phase 2 studies of atumelnant in CAH and ACTH-dependent Cushing’s syndrome, respectively, are anticipated by the end of 2024.
Submission of a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) seeking regulatory approval of paltusotine for the treatment of acromegaly is on track for the second half of 2024.
Initiation of a Phase 3 program of paltusotine for carcinoid syndrome is expected by the end of 2024, following consultation with the FDA.
Additional research pipeline updates are expected by the end of 2024.
Second Quarter 2024 Financial Results
Research and development expenses were $58.3 million for the three months ended June 30, 2024, compared to $40.6 million for the same period in 2023. The increase was primarily attributable to higher personnel costs and manufacturing and development activities, both of which were driven by the advancement of our clinical programs and the expansion of our preclinical portfolio.
General and administrative expenses were $24.8 million for the three months June 30, 2024, compared to $13.3 million for the same period in 2023. The increase was primarily driven by higher personnel and commercial planning costs.
Net loss for the three months ended June 30, 2024, was $74.1 million, compared to a net loss of $51.0 million for the same period in 2023.
Revenues were $0.4 million for the three months ended June 30, 2024, compared to $1.0 million for the same period in 2023. Revenues during the current year’s quarter were derived from the paltusotine licensing arrangement with our Japanese partner, Sanwa Kagaku Kenkyusho.
Unrestricted cash, cash equivalents, and investments totaled $863.0 million as of June 30, 2024, compared to $558.6 million as of December 31, 2023. Based on its current projections, Crinetics expects that its cash, cash equivalents and short-term investments will be sufficient to fund its current operating plan into 2028.
Conference Call and Webcast Details
Management will hold a live conference call and webcast today, Thursday, August 8, 2024 at 4:30 p.m. ET. To participate, please dial 1-800-267-6316 (domestic) or 1-203-518-9783 (international) and refer to Conference ID CRNXQ2. To access the webcast, click here. Following the live event, a replay of the call will be available on the Investors section of the Company’s website.

*Proposed international nonproprietary name under review.

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 Scholar Rock (NASDAQ: SRRK), a late-stage biopharmaceutical company focused on advancing innovative treatments for spinal muscular atrophy (SMA), cardiometabolic disorders, and other serious diseases where protein growth factors play a fundamental role, reported financial results and corporate updates for the second quarter ended June 30, 2024 (Press release, Scholar Rock, AUG 8, 2024, View Source [SID1234645625]).

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"Scholar Rock continues to execute across our portfolio of highly selective myostatin inhibition programs, further cementing our position as the global leader in harnessing the life-changing potential of TGF-beta superfamily biology," said Jay Backstrom, M.D., MPH, President & Chief Executive Officer of Scholar Rock. "With the only muscle-targeted program to demonstrate clinical proof-of-concept in SMA, our confidence in our lead program apitegromab continues to be supported by the clinical data generated over the past four years. At 48 months, over 90% of TOPAZ patients with nonambulatory SMA remained on apitegromab treatment on top of SMN therapy and we continued to observe sustained clinical benefit. We look forward to reporting topline data from the Phase 3 SAPPHIRE trial of apitegromab in SMA in the fourth quarter of this year."

Dr. Backstrom continued, "In addition, we are pleased with the progress of our cardiometabolic program. The enrollment of the Phase 2 proof-of-concept EMBRAZE study evaluating apitegromab in obesity has been advancing ahead of schedule and as a result, we are updating our guidance for topline data to the second quarter of 2025. We also presented new preclinical data supporting SRK-439’s potential to help patients retain lean muscle mass at our investor event in May and at the ADA 84th Scientific Sessions in June. The hallmark of our approach in designing both apitegromab and SRK-439 is the exquisite selectivity for pro- and latent forms of myostatin. Our data in SMA suggest that this selectivity matters for patients, and we are excited to show how SRK-439 can become an integral component of the treatment and management of obesity helping to preserve lean muscle mass for sustainable and healthy weight loss management."

Company Highlights and Upcoming Milestones

SMA Program

Apitegromab is an investigational, fully human monoclonal antibody that inhibits myostatin activation by selectively binding the pro- and latent forms of myostatin in skeletal muscle and is being developed as a potential first muscle-targeted therapy for the treatment of SMA. Apitegromab is the only muscle-targeted therapy to show clinical proof-of-concept in SMA.

● On track to report topline data from Phase 3 SAPPHIRE clinical trial in 4Q 2024. If the trial is successful and apitegromab is approved, the Company expects to initiate a commercial product launch in 2025.
● Reported that long-term apitegromab data continued to show substantial and sustained motor function improvements over 48 months1. The mean change in Hammersmith Functional Motor Scale (HFMSE) from baseline in nonambulatory patients (ages 2-21) on combination therapy (nusinersen and 20 mg/kg of apitegromab) was 5.3 points (95% CI: 1.5, 9.2; n=23), and for patients 2-12 was 6.4 points (95% CI: 1.8, 11.0, n=19). The mean change in RULM for the 2-21 age group was 3.6 points (95% CI: 2.0, 5.3; N=22) and for the 2-12 age group was 4.5 (95% CI: 2.7, 6.3; n=18). Of the 35 participants in the pooled nonambulatory population, 33 remained in the study over 4 years. The data analysis excluded the scores of 11 patients after undergoing scoliosis surgery, a known confounding factor for motor function assessment. Additional details will be discussed on the conference call this morning.

12-Month Data

24-Month Data

36-Month Data

48-Month Data

Age 2-21 Years Mean Change from Baseline in HFMSE (95% Confidence Interval)

3.6 points

(1.2, 6.0)

n=32

4.2 points

(1.9, 6.6)

n=29

4.0 points

(1.0, 6.9)

n=28

5.3 points

(1.5, 9.2)

n=23

Age 2-12 Years Mean Change from Baseline in HFMSE (95% Confidence Interval)

4.6 points

(1.8, 7.4)

n=26

5.2 points

(2.3, 8.0)

n=23

4.8 points

(1.3, 8.3)

n=23

6.4 points

(1.8, 11.0)

n=19

Age 2-21 Years Mean Change from Baseline in

RULM (95% Confidence Interval)

1.3 points

(0.2, 2.3)

n=31

2.3 points

(1.2, 3.3)

n=31

2.4 points

(1.1, 3.7)

n=27

3.6 points

(2.0, 5.3)

n=22

Age 2-12 Years Mean Change from Baseline in

RULM (95% Confidence Interval)

1.2 points

(0.1, 2.4)

n=25

2.2 points

(1.0, 3.5)

n=25

2.8 points

(1.4, 4.2)

n=22

4.5 points

(2.7, 6.3)

n=18

1. For the 48-month evaluation, an observed case analysis was conducted using available data by analysis timepoint, censoring any HFMSE and RULM assessments after the patient received scoliosis surgery. The analysis population pooled the nonambulatory patients (Cohorts 2 and 3) and included patients receiving either low dose (2 mg/kg) or high dose (20 mg/kg) apitegromab (inclusive of patients in Cohort 3 who switched from 2 mg/kg to 20 mg/kg in Year 2). A total of 11 patients in the population had scoliosis surgery during the study and their data was excluded from any HFMSE or RULM assessments at 48 months. Visit windows were applied to utilize data from unscheduled or early termination visits if the patient was missing the HFMSE or RULM total score at the scheduled visit.

● The ONYX open-label, multicenter extension study is ongoing. The extension study is evaluating the long-term safety and efficacy of apitegromab in patients with Type 2 and Type 3 SMA who completed the TOPAZ or SAPPHIRE trials. More than 90 percent of patients on combination therapy in the TOPAZ study have completed 4 years of apitegromab treatment and enrolled into ONYX.

Cardiometabolic Program

SRK-439 is a novel, preclinical, investigational myostatin inhibitor that has high in vitro affinity for pro- and latent myostatin and maintains myostatin specificity (i.e., no GDF11 or Activin A binding), and is initially being developed for the treatment of obesity.

● Presented preclinical data from the SRK-439 program. In May, the Company announced new preclinical data comparing SRK-439 and an anti-activin receptor II (anti-ActRII) antibody that supported SRK-439’s potential as best in class in preserving lean muscle mass in patients on GLP-1 receptor agonists (GLP-1 RAs). In June, the company presented new preclinical data at the American Diabetes Association 84th Scientific Sessions supporting the potential of SRK-439 to increase lean mass and contribute to a favorable body composition following withdrawal from GLP-1 RA treatment.
● Initiated Phase 2 EMBRAZE proof-of-concept trial with apitegromab in combination with a GLP-1 receptor agonist (GLP-1 RA) in obesity in May. The Phase 2 trial is a randomized, double-blind, placebo-controlled, multi-center study to evaluate the effect of apitegromab, a highly selective investigational myostatin inhibitor, to preserve muscle mass as an adjunctive therapy in overweight and obese adults who are taking a GLP-1 RA. Data are expected in the second quarter of 2025 and will be used to guide clinical development of SRK-439. The Company plans to file an IND for SRK-439 for the treatment of obesity in 2025.

Other Pipeline Updates

● New SRK-181 data from the Phase 1 DRAGON proof-of-concept trial presented at the ASCO (Free ASCO Whitepaper) Annual Meeting in June. SRK-181 is an investigational selective inhibitor of latent TGFβ-1 activation and developed with the aim of overcoming resistance to checkpoint therapy in patients with advanced cancer. Clinical data showed encouraging responses in heavily pretreated and anti-PD-(L)1 resistant patients across multiple tumor types. Enrollment of the DRAGON trial was completed in December 2023, and patients who remain on the study continue to be treated.
● Published data on SRK-373 was featured on the cover of Science Signaling in July. The article describes the selectivity of SRK-373 for LTBP-presented TGFβ-1, as well as efficacy data from two preclinical models that establish the feasibility of selectively targeting this particular form of TGFβ-1 for the treatment of fibrosis. SRK-373 is an investigational selective inhibitor of matrix associated TGFβ-1 in development for the treatment of fibrosis.

Second Quarter 2024 Financial Results

For the quarter ended June 30, 2024, net loss was $58.5 million or $0.60 per share compared to a net loss of $37.9 million or $0.47 per share for the quarter ended June 30, 2023.

● The Company did not record any revenue for the quarter ended June 30, 2024 or for the quarter ended June 30, 2023.
● Research and development expense was $42.4 million for the quarter ended June 30, 2024, compared to $26.9 million for the quarter ended June 30, 2023. The increase was primarily attributable to clinical trial and employee compensation costs.
● General and administrative expense was $17.1 million for the quarter ended June 30, 2024, compared to $12.2 million for the quarter ended June 30, 2023. The increase was due to employee-related costs.
● As of June 30, 2024, Scholar Rock had cash, cash equivalents, and marketable securities of approximately $190.5 million, which is expected to fund the Company’s anticipated operating and capital expenditure requirements into the second half of 2025.

"Our year-to-date progress across our pipeline of industry-leading myostatin inhibition programs, combined with our highly experienced and disciplined team, provides us with a robust foundation for growth as we advance towards multiple milestones and our potential evolution into a commercial-stage company," said Ted Myles, Chief Operating Officer and Chief Financial Officer of Scholar Rock.

Conference Call Information
Management will provide an update on the Company and discuss second quarter 2024 results via conference call on Thursday, August 8 at 8:15 am ET. To access the live conference call, participants may register here. The live audio webcast of the call will be available under "Events and Presentations" in the Investor Relations section of the Scholar Rock website at View Source To participate via telephone, please register in advance here. Upon registration, all telephone participants will receive a confirmation email detailing how to join the conference call, including the dial-in number along with a unique passcode and registrant ID that can be used to access the call. An archived replay of the webcast will be available on the Company’s website for approximately 90 days.

About Apitegromab

Apitegromab is an investigational fully human monoclonal antibody inhibiting myostatin activation by selectively binding the pro- and latent forms of myostatin in the skeletal muscle. It is the first muscle-targeted treatment candidate to demonstrate clinical proof-of-concept in spinal muscular atrophy (SMA). Myostatin, a member of the TGFβ superfamily of growth factors, is expressed primarily by skeletal muscle cells, and the absence of its gene is associated with an increase in muscle mass and strength in multiple animal species, including humans. Scholar Rock believes that its highly selective targeting of pro- and latent forms of myostatin with apitegromab may lead to a clinically meaningful improvement in motor function in patients with SMA. The U.S. Food and Drug Administration (FDA) has granted Fast Track, Orphan Drug and Rare Pediatric Disease designations, and the European Medicines Agency (EMA) has granted Priority Medicines (PRIME) and Orphan Medicinal Product designations, to apitegromab for the treatment of SMA. The efficacy and safety of apitegromab have not been established and apitegromab has not been approved for any use by the FDA or any other regulatory agency.

About the Phase 3 SAPPHIRE Trial

SAPPHIRE is an ongoing randomized, double-blind, placebo-controlled, Phase 3 clinical trial evaluating the safety and efficacy of apitegromab in nonambulatory patients with Types 2 and 3 SMA who are receiving SMN-targeted therapy (either nusinersen or risdiplam). SAPPHIRE targeted enrolling approximately 156 patients aged 2-12 years old in the main efficacy population. These patients were randomized 1:1:1 to receive for 12 months either apitegromab 10 mg/kg, apitegromab 20 mg/kg, or placebo by intravenous (IV) infusion every 4 weeks. An exploratory population that targeted enrolling up to 48 patients aged 13-21 years old will also separately be evaluated. These patients were randomized 2:1 to receive either apitegromab 20 mg/kg or placebo. For more information about SAPPHIRE, visit www.clinicaltrials.gov. Apitegromab has not been approved for any use by the US FDA or any other health authority, and its safety and efficacy have not been established.

About EMBRAZE

EMBRAZE is a randomized, double-blind, placebo-controlled, Phase 2 proof-of-concept trial evaluating the efficacy, safety and pharmacokinetics of apitegromab in adults with a body mass index (BMI) of >27 (overweight) or a BMI of >30 (obese) and taking a GLP-1 RA (tirzepatide or semaglutide). The target enrollment of EMBRAZE is 100 subjects aged 18-65 who are overweight or obese without diabetes. As part of the study design, the treatment period is 24 weeks, and all subjects will receive a GLP-1 RA. In addition, all subjects will be randomized 1:1 to receive either apitegromab or placebo by intravenous (IV) infusion every four weeks during the 24-week treatment period. The primary endpoint is change from baseline at Week 24 in lean mass assessed by dual-energy X-ray absorptiometry. Secondary endpoints include additional weight loss measures, safety and tolerability, and pharmacokinetic outcomes. Exploratory endpoints at Weeks 24 and 32 include cardiometabolic parameters (e.g. HbA1c), body composition, and physical function.

About SRK-439

SRK-439 is a novel, preclinical, investigational myostatin inhibitor that has high in vitro affinity for pro- and latent myostatin and maintains myostatin specificity (i.e., no GDF11 or Activin-A binding), and is initially being developed for the treatment of cardiometabolic disorders, including obesity. Based on preclinical data, SRK-439 has the potential to support healthier weight management by preserving lean mass during weight loss. The efficacy and safety of SRK-439 have not been established and SRK-439 has not been approved for any use by the FDA or any other regulatory agency.