On February 14, 2025 Fate Therapeutics, Inc. (NASDAQ: FATE), a clinical-stage biopharmaceutical company dedicated to bringing a first-in-class pipeline of induced pluripotent stem cell (iPSC)-derived cellular immunotherapies to patients with cancer and autoimmune diseases, reported that the Company will participate in the following upcoming investor conferences (Press release, Fate Therapeutics, FEB 14, 2025, View Source [SID1234650284]):

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H.C. Wainwright 3rd Annual Cell Therapy Virtual Conference, including a fireside chat at 1:30 PM ET on Tuesday, February 25, 2025
TD Cowen 45th Annual Health Care Conference, including a company presentation at 11:50 AM ET on Monday, March 3, 2025 in Boston, Massachusetts
Barclays 27th Annual Global Healthcare Conference, including a fireside chat at 8:30 AM ET on Tuesday, March 11, 2025 in Miami, Florida
Leerink Partners Global Healthcare Conference, including a fireside chat at 11:20 AM ET on Wednesday, March 12, 2025 in Miami, Florida
A live webcast, if recorded, of each presentation can be accessed under "Events & Presentations" in the Investors section of the Company’s website at www.fatetherapeutics.com. The archived webcast will be available on the Company’s website shortly after the event.

On February 14, 2025 IN8bio, Inc. (Nasdaq: INAB), a clinical-stage biopharmaceutical company developing innovative gamma-delta T cell therapies, reported Phase 1 data on its allogeneic gamma-delta T cell therapy, INB-100, at the 2025 Transplantation & Cellular Therapy (TCT) Meetings in Hawaii (Press release, In8bio, FEB 14, 2025, View Source [SID1234650285]). The data, previously announced, reinforce INB-100’s potential to significantly reduce post-transplant relapse in high-risk acute myeloid leukemia (AML) patients, positioning this gamma-delta T cell therapy as a promising approach in hematologic oncology.

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The latest findings demonstrate that INB-100 continues to deliver long-term remissions, with no AML patient relapses observed to date with a median follow-up of 20.1 months. The 1-year progression-free survival (PFS) rate across all leukemia patients stands at 90.9%, and 1-year overall survival (OS) is 100%, outperforming real-world historical controls. These data demonstrate that results for INB-100 do not appear to be due to imbalances in patient selection criteria, the performance of the individual clinical centers or driven by specific transplant or lymphodepletion protocols. These data underscore INB-100’s potential to reshape post-transplant care by leveraging gamma-delta T cells to enable sustained cancer cell surveillance and long-term remissions.

"AML patients undergoing allogeneic HSCT face high relapse rates with limited post-transplant therapeutic options," said William Ho, Chief Executive Officer and co-founder of IN8bio. "The durability of response and safety profile observed to date with INB-100 support its potential to set a new standard in post-transplant leukemia management."

"Despite decades of progress in transplantation, relapse remains the primary driver of mortality in AML patients post-HSCT. The INB-100 data showing durable remission without maintenance therapy is highly encouraging," said Dr. Michael Bishop, Director of the Hematopoietic Cellular Therapy Program, Director of the David and Etta Jonas Center for Cellular Therapy, and Professor of Medicine at the University of Chicago and IN8bio Scientific Advisory Board member.

Key Phase 1 INB-100 Findings:

Zero Relapses in AML Patients: No relapses observed in any AML patient treated with INB-100, with a median follow-up of over 20 months.
Superior 1-Year Survival Rates: PFS at 90.9%, OS at 100%.
Favorable Safety Profile: No cytokine release syndrome (CRS), neurotoxicity (ICANS), or Dose Limiting Toxicities (DLT’s). No treatment-related deaths.
Gamma Delta T Cell Persistence and Expansion: Evidence of in vivo expansion and long-term persistence, reinforcing the therapy’s potential to maintain immune surveillance against residual leukemic cells.
With approximately 20,000 new AML cases and ~11,500 deaths annually in the U.S., AML remains an area of high unmet medical need. Post-HSCT relapse occurs in up to 50% of patients, highlighting the urgency for novel, more durable therapeutic approaches. INB-100 harnesses the innate tumor-targeting properties of gamma-delta T cells to improve long-term outcomes, potentially filling a critical treatment gap.

IN8bio is accelerating patient enrollment in the INB-100 program and expects to complete enrollment of the expansion cohort in 2025. The company’s FDA discussions confirmed that relapse-free survival (RFS) is an acceptable primary endpoint for a future potentially pivotal randomized controlled trial in AML patients.

IN8bio recently hosted a Key Opinion Leader webinar discussing the latest developments in gamma-delta T cell therapy and the promising INB-100 clinical data. The webinar featured insights including Dr. Michael Bishop. A replay of the February 11, 2025 webinar is accessible here on the company’s website.

On February 14, 2025 Moderna, Inc. (NASDAQ:MRNA) reported financial results and provided business updates for the fourth quarter and fiscal year 2024 (Press release, Moderna Therapeutics, FEB 14, 2025, View Source/news/news-details/2025/Moderna-Reports-Fourth-Quarter-and-Fiscal-Year-2024-Financial-Results-and-Provides-Business-Updates/default.aspx" target="_blank" title="View Source/news/news-details/2025/Moderna-Reports-Fourth-Quarter-and-Fiscal-Year-2024-Financial-Results-and-Provides-Business-Updates/default.aspx" rel="nofollow">View Source [SID1234654339]).

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"We have made progress in 2024 across our late-stage pipeline and cost reduction efforts. Our team successfully filed three Biologics License Applications in the final months of the year and reduced our costs by 27 percent compared to 2023," said Stéphane Bancel, Chief Executive Officer of Moderna. "In 2025, we remain focused on driving sales, delivering up to 10 product approvals through 2027, and expanding cost efficiencies across our business. By the end of 2025, we aim to remove nearly $1 billion in costs. With strong momentum in our late-stage pipeline, we anticipate multiple approvals starting this year, along with key Phase 3 readouts that will support our long-term growth."

Recent progress includes:

Commercial Updates

Moderna is entering 2025 with two approved products, Spikevax and mRESVIA.

COVID-19: The Company reported $923 million in Spikevax sales in the fourth quarter of 2024, which includes $244 million of U.S. sales and $679 million of international sales. Spikevax sales for the full year 2024 were $3.1 billion.

RSV: The Company reported $15 million in mRESVIA sales in the fourth quarter of 2024. mRESVIA sales for the full year 2024 were $25 million. Moderna’s RSV vaccine for adults aged 60 years and older has been approved in the United States, Canada, EU, Norway, Iceland, Liechtenstein, the United Arab Emirates, Qatar and Taiwan.

Fourth Quarter 2024 Financial Results

Revenue: Total revenue for the fourth quarter of 2024 was $1.0 billion, compared to $2.8 billion in the same period in 2023. Net product sales for the fourth quarter of 2024 were $938 million, reflecting a 66% year-over-year decrease. The decrease was primarily due to the earlier launch of the updated COVID-19 vaccine in the United States, which shifted sales into the third quarter. The U.S. Food and Drug Administration (FDA) approval granted three weeks earlier than in the previous year enabled the Company to meet demand more effectively ahead of the fourth quarter. Additionally, international sales were lower compared to the same period in 2023, reflecting the continued phase-out of advance purchase agreements.

Cost of Sales: Cost of sales for the fourth quarter of 2024 was $739 million, which included third-party royalties of $45 million, inventory write-downs of $193 million, and wind-down costs of $259 million, including a non-cash charge of $238 million related to the termination of a contract manufacturing agreement during the quarter. Compared to the same period in 2023, cost of sales decreased by $190 million, or 20%, primarily due to lower third-party royalties from reduced product sales and a decline in inventory write-downs. Despite the overall reduction in cost of sales, cost of sales as a percentage of net product sales increased to 79%, compared to 33% in the fourth quarter of 2023, reflecting the impact of lower net product sales. Excluding the $238 million wind-down costs related to the termination of the contract manufacturing agreement, cost of sales as a percentage of net product sales would have been 53%.

Research and Development Expenses: Research and development expenses for the fourth quarter of 2024 decreased by 20% to $1.1 billion, compared to the fourth quarter in 2023. The decrease was primarily driven by lower clinical development and manufacturing expenses related to the COVID-19, RSV, seasonal flu, and combination vaccine programs, partially offset by increased spending on the norovirus and individualized neoantigen therapy (INT) programs. The reduction in flu program expenses reflects funding provided by Blackstone Life Sciences during the quarter. The absence of a $120 million upfront payment for the strategic research and development collaboration with Immatics recorded in the fourth quarter of 2023, also contributed to the year-over-year decline.

Selling, General and Administrative Expenses: Selling, general and administrative expenses for the fourth quarter of 2024 decreased by 25% to $351 million, compared to the fourth quarter in 2023. The reduction was primarily driven by lower consulting and outside services, reflecting the Company’s continued focus on cost management and operational efficiencies achieved through prior investments in foundational capabilities.

Income Taxes: The Company recognized an income tax benefit of $64 million for the fourth quarter of 2024, compared to $147 million in the same period last year. In both periods, the income tax benefit was not material as the Company continues to maintain a global valuation allowance against most of its deferred tax assets.

Net (Loss) Income: Net loss was $(1.1) billion for the fourth quarter of 2024, compared to net income of $217 million for the fourth quarter of 2023.

(Loss) Earnings Per Share: Loss per share was $(2.91) for the fourth quarter of 2024, compared to earnings per share of $0.55 for the fourth quarter of 2023.

Cash Position: Cash, cash equivalents and investments as of December 31, 2024, were $9.5 billion, compared to $9.2 billion as of September 30, 2024. The increase during the quarter was primarily attributable to the timing of accounts receivable collections.

Full Year 2024 Financial Results

Revenue: Total revenue was $3.2 billion for the full year 2024, compared to $6.8 billion in 2023. The decrease in total revenue was mainly due to lower sales of the Company’s COVID-19 vaccine. Net product sales for 2024 were $3.1 billion, a decrease of 53% from 2023. This decline reflects the transition to a seasonal commercial market for COVID-19 vaccines, with significantly lower sales volumes in Europe and other international markets as advance purchase agreements phased out. In the U.S., product sales remained consistent year-over-year, with an approximately $216 million benefit from the reversal of prior-year sales provisions. Excluding this adjustment, U.S. sales volumes decreased slightly compared to 2023, primarily due to lower vaccination rates and increased market competition. Additionally, the Company commenced sales of its RSV vaccine during the third quarter of 2024, generating $25 million in revenue for the year.

Cost of Sales: Cost of sales for the full year 2024 was $1.5 billion, or 47% of net product sales, inclusive of third-party royalties of $155 million, inventory write-downs of $495 million, wind-down costs of $263 million, and unutilized manufacturing capacity of $105 million. This represents a $3.2 billion decrease, compared to $4.7 billion in 2023, when cost of sales was 70% of net product sales. The decline reflects the impact of a strategic cost initiative launched in the third quarter of 2023 to resize manufacturing operations, which incurred $1.6 billion in charges in 2023. In addition to the initiative, cost of sales also benefited from lower inventory write-downs and reduced unutilized manufacturing capacity, contributing to improved efficiency. Of the wind-down costs incurred in 2024, a non-cash charge of $238 million related to the termination of a contract manufacturing agreement during the fourth quarter. Excluding the $238 million related to this termination, cost of sales as a percentage of net product sales for 2024 would have been approximately 39%.

Research and Development Expenses: Research and development expenses decreased by 6% to $4.5 billion for 2024, compared to 2023. The decrease was primarily driven by lower clinical trial and clinical manufacturing expenses, as well as reduced upfront payments for collaboration agreements. These reductions were partially offset by the purchase of two priority review vouchers during the year.

Selling, General and Administrative Expenses: Selling, general and administrative expenses decreased by 24% to $1.2 billion for 2024, compared to 2023. The decrease was primarily driven by reductions in consulting and outside services across all functions, as well as lower commercial and marketing expenses. These reductions reflect the Company’s focus on cost discipline and operational efficiencies gained by reducing reliance on external consultants and bringing more functions in-house.

Income Taxes: Income tax benefit for the full year 2024 was $46 million, compared to an income tax expense of $772 million in 2023. The shift was primarily due to the establishment of a global valuation allowance on most deferred tax assets in the third quarter of 2023.

Net Loss: Net loss for the full year 2024 was $(3.6) billion, compared to $(4.7) billion in 2023.

Loss Per Share: Loss per share for the full year 2024 was $(9.28), compared to $(12.33) in 2023.

Cash Position: Cash, cash equivalents and investments as of December 31, 2024, and December 31, 2023, were $9.5 billion and $13.3 billion, respectively. The decrease in cash during 2024 was largely attributable to the full year’s operating loss.

2025 Financial Framework

Revenue: The Company reiterates 2025 expected revenue of $1.5 to $2.5 billion. Moderna expects revenue of approximately $0.2 billion in the first half of the year, reflecting the seasonality of its respiratory business.

Cost of Sales: Cost of sales for 2025 is expected to be approximately $1.2 billion.

Research and Development Expenses: Full-year 2025 research and development expenses are anticipated to be approximately $4.1 billion.

Selling, General and Administrative Expenses: Selling, general and administrative expenses for 2025 are projected to be approximately $1.1 billion.

Income Taxes: The Company continues to expect its full-year tax expense to be negligible.

Capital Expenditures: Capital expenditures for 2025 are expected to be approximately $0.4 billion.

Cash and Investments: Year-end cash and investments for 2025 are projected to be approximately $6 billion.

Recent Progress and Upcoming Late-Stage Pipeline Milestones

The Company remains focused on a prioritized research and development portfolio, delivering up to 10 product approvals through 2027.

Respiratory vaccines:

Next-generation COVID-19 vaccine: Moderna shared positive Phase 3 vaccine efficacy and immunogenicity data for its next-generation COVID-19 vaccine (mRNA-1283) at its R&D Day event in September 2024. The Company has filed for regulatory approval of mRNA-1283 with the FDA using a priority review voucher. The FDA has accepted Moderna’s Biologics License Application (BLA) for mRNA-1283 and has assigned a Prescription Drug User Fee Act (PDUFA) goal date of May 31, 2025.

Respiratory syncytial virus (RSV) vaccine: Moderna received regulatory approval of its RSV vaccine mRESVIA (mRNA-1345) for adults aged 60 years and older in 2024. The Company shared positive Phase 3 data for mRNA-1345 in high-risk adults aged 18-59 at its 2024 R&D Day event and has since submitted an application to the FDA for regulatory approval using a priority review voucher. The FDA has accepted Moderna’s BLA and has assigned a PDUFA goal date of June 12, 2025.

Seasonal flu + COVID vaccine: Moderna shared positive Phase 3 immunogenicity data for its flu/COVID combination vaccine (mRNA-1083) for adults aged 50 years and older at its 2024 R&D Day event. The Company has filed with the FDA for regulatory approval of mRNA-1083, which may require vaccine efficacy data from Moderna’s ongoing Phase 3 seasonal flu vaccine study.

Seasonal flu vaccine: Moderna has shared positive Phase 3 immunogenicity and safety data for its seasonal flu vaccine (mRNA-1010). The Company is conducting a two-season Phase 3 efficacy study (P304), where the timing of the efficacy readout depends on case accrual and could happen in the current season.

Latent and other vaccines:

Cytomegalovirus (CMV) vaccine: The pivotal Phase 3 study of Moderna’s CMV vaccine candidate (mRNA-1647) is fully enrolled and accruing cases, evaluating its efficacy, safety and immunogenicity in the prevention of primary infection in women of childbearing age. The Data Safety Monitoring Board (DSMB) met to review the initial study data and has informed the Company that the criterion for early efficacy was not met. The DSMB recommended that the study continue as planned. The Company remains blinded and anticipates efficacy data from the study in 2025.

Norovirus vaccine: The two-season Phase 3 study evaluating the efficacy, safety and immunogenicity of Moderna’s trivalent vaccine against norovirus (mRNA-1403) is fully enrolled in the Northern Hemisphere and the Company is preparing second season enrollment in the Southern Hemisphere. The trial is currently on FDA clinical hold following a single adverse event report of a case of Guillain-Barré syndrome, which is currently under investigation. The Company does not expect an impact on the study’s efficacy readout timeline as enrollment in the Northern Hemisphere has already been completed. The timing of the Phase 3 readout will be dependent on case accruals.

Oncology therapeutics:

Individualized Neoantigen Therapy (INT): Moderna continues to demonstrate the potential clinical benefit of its individualized neoantigen therapy (INT) (mRNA-4157). In collaboration with Merck, the Phase 3 clinical trial for adjuvant melanoma is fully enrolled. Two Phase 3 studies for non-small cell lung cancer are enrolling. A randomized Phase 2 study for high-risk muscle invasive bladder cancer is enrolling, and a randomized Phase 2 study for adjuvant renal cell carcinoma is enrolling.

Rare disease therapeutics:

Propionic acidemia (PA) therapeutic: In an ongoing Phase 1/2 study designed to evaluate safety and pharmacology in trial participants with PA, Moderna’s investigational therapeutic (mRNA-3927) has been generally well-tolerated to date with no events meeting protocol-defined dose-limiting toxicity criteria. Early results suggest potential decreases in annualized metabolic decompensation event (MDE) frequency compared to pre-treatment, and the majority of patients have elected to continue on the open label extension study. The Company began generating registrational trial data in 2024.

Methylmalonic acidemia (MMA) therapeutic: Moderna’s investigational therapeutic for MMA (mRNA-3705) has been selected by the FDA for the Support for Clinical Trials Advancing Rare Disease Therapeutics (START) pilot program. The FDA and Moderna have agreed on the pivotal study design. The Company expects to start a registrational study in 2025.

Moderna Corporate Updates

Published Moderna CEO Stéphane Bancel’s annual letter to shareholders on January 6, 2025.

Provided business and pipeline updates at the 43rd Annual J.P. Morgan Healthcare Conference on January 13, 2025.

Announced updates on the Company’s pandemic influenza program.

Entered into a framework agreement with the European Union, Norway and North Macedonia that provides 17 participating countries a framework for tendering for Moderna’s mRNA COVID-19 vaccine for up to four years should there be demand in addition to the current competitor contract.

Scheduled the Moderna Annual Meeting of Shareholders to be held on Wednesday, April 30, 2025, at 8:00 a.m. ET.

Company Accolades

Moderna topped BioSpace’s Best Places to Work in Biopharma ranking for fourth consecutive year.

Key 2025 Investor and Analyst Event Dates

Analyst Day: November 20

Investor Call and Webcast Information

Moderna will host a live conference call and webcast at 8:00 a.m. ET on February 14, 2025. To access the live conference call via telephone, please register at the link below. Once registered, dial-in numbers and a unique pin number will be provided. A live webcast of the call will also be available under "Events and Presentations" in the Investors section of the Moderna website.

Telephone: View Source

Webcast: View Source

The archived webcast will be available on Moderna’s website approximately two hours after the conference call and will be available for one year following the call.

About Moderna

Moderna is a leader in the creation of the field of mRNA medicine. Through the advancement of mRNA technology, Moderna is reimagining how medicines are made and transforming how we treat and prevent disease for everyone. By working at the intersection of science, technology and health for more than a decade, the company has developed medicines at unprecedented speed and efficiency, including one of the earliest and most effective COVID-19 vaccines.

Moderna’s mRNA platform has enabled the development of therapeutics and vaccines for infectious diseases, immuno-oncology, rare diseases and autoimmune diseases. With a unique culture and a global team driven by the Moderna values and mindsets to responsibly change the future of human health, Moderna strives to deliver the greatest possible impact to people through mRNA medicines. For more information about Moderna, please visit modernatx.com and connect with us on X (formerly Twitter), Facebook, Instagram, YouTube and LinkedIn.

On February 14, 2025 Outlook Therapeutics, Inc. (Nasdaq: OTLK), a biopharmaceutical company that achieved regulatory approval in the European Union (EU) and the United Kingdom (UK) for the first authorized use of an ophthalmic formulation of bevacizumab for the treatment of wet age-related macular degeneration (wet AMD), reported financial results for the first quarter of fiscal year 2025 and provided a corporate update (Press release, Outlook Therapeutics, FEB 14, 2025, View Source [SID1234650286]).

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"With all of the recent progress made at Outlook Therapeutics and the upcoming milestones over the next few months, we expect to be a very different company by the end of 2025," commented Lawrence Kenyon, Chief Financial Officer and Interim Chief Executive Officer of Outlook Therapeutics. "In 2025, we plan to start realizing our goal of providing patients, physicians and payers with an approved ophthalmic formulation of bevacizumab. This year, we anticipate beginning to generate the first revenue for Outlook Therapeutics with the launch of LYTENAVA in Germany and the UK and our BLA is on track for resubmission this quarter."

Upcoming Anticipated Milestones

Resubmission of the ONS-5010 BLA targeted for Q1 CY2025;
Initial commercial launches in Germany and the UK planned to commence in Q2 CY2025; and
Potential for US FDA approval of ONS-5010 in Q3 CY2025.
LYTENAVA (bevacizumab gamma) European Commercial Update

In May 2024, the European Commission granted Marketing Authorization for LYTENAVA (bevacizumab gamma) for the treatment of wet AMD in the EU. Additionally, in July 2024, the UK Medicines and Healthcare products Regulatory Agency (MHRA) granted Marketing Authorization for LYTENAVA (bevacizumab gamma) for the same indication in the UK. In December 2024, the National Institute for Health and Care Excellence (NICE) recommended LYTENAVA (bevacizumab gamma) as an option for the treatment of wet AMD. Plans for a potential 2025 launch in Germany and the UK are ongoing. Outlook Therapeutics remains confident that ONS-5010 / LYTENAVA is an important therapy for the treatment of wet AMD in place of off-label repackaged bevacizumab that has not received regulatory approval for use in retina diseases such as wet AMD. Outlook Therapeutics intends to launch LYTENAVA (bevacizumab gamma) in Germany and the UK in the second quarter of calendar year 2025.

LYTENAVA (bevacizumab gamma) is the first and only authorized ophthalmic formulation of bevacizumab for use in treating wet AMD in adults in the EU and UK. Currently, over 2.5 million injections of off-label, repackaged bevacizumab are administered to patients across Europe each year, with about one third of these injections in Germany alone. In Germany, there are an estimated 1.6 million anti-VEGF retina injections each year, with over half of those injections representing use of off-label, repackaged bevacizumab. For Germany, LYTENAVA (bevacizumab gamma) represents an opportunity for patients there to receive an approved, cGMP produced bevacizumab for the first time. The UK market represents approximately 1.3 million anti-VEGF retina injections each year, but use of repackaged bevacizumab is not authorized. In the UK, LYTENAVA (bevacizumab gamma) represents the first time that most patients will have access to the therapy.

Authorization may also be sought in other European countries, Japan, and elsewhere. Outlook Therapeutics has entered into a strategic collaboration with Cencora (formerly AmerisourceBergen) to support the commercial launch of LYTENAVA globally following regulatory approvals. The collaborative and integrated approach is designed to support market access and efficient distribution of LYTENAVA to benefit all stakeholders, including retina specialists, providers and patients.

ONS-5010 / LYTENAVA (bevacizumab-vikg) Clinical and Regulatory Update

Outlook Therapeutics believes that the complete data set for NORSE EIGHT, combined with the data from the other NORSE clinical trials, provides the required clinical evidence to support approval of the ONS-5010 BLA in the US. Outlook Therapeutics plans to resubmit the BLA for ONS-5010 in the first quarter of calendar 2025. If approved by the U.S. Food and Drug Administration (FDA), Outlook Therapeutics plans to commercialize ONS-5010 / LYTENAVA (bevacizumab-vikg) directly in the US.

In November 2024, Outlook Therapeutics reported that in the NORSE EIGHT clinical trial, the second of two adequate and well controlled clinical trials evaluating ONS-5010 in wet AMD patients, ONS-5010 did not meet the pre-specified non-inferiority endpoint at week 8 set forth in the special protocol assessment (SPA) with the FDA. NORSE EIGHT is a randomized, controlled, parallel-group, masked, non-inferiority study of approximately 400 newly diagnosed, wet AMD subjects randomized in a 1:1 ratio to receive 1.25 mg ONS-5010 / LYTENAVA or 0.5 mg ranibizumab intravitreal injections. Subjects received injections at Day 0 (randomization), Week 4, and Week 8 visits. The primary endpoint is the mean change in best corrected visual acuity (BCVA) from baseline to week 8.

In January 2025, Outlook Therapeutics announced results from the completed analysis of the 12-week safety and efficacy results for NORSE EIGHT, which indicated that ONS-5010 demonstrated clinically meaningful anatomic and functional improvements at each study timepoint. Results from the 12-week analysis demonstrated the difference in the mean between ONS-5010 and ranibizumab was -1.009 best corrected visual acuity (BCVA) letters with a 95% confidence interval of (-2.865, 0.848) in the NORSE EIGHT trial. Applying the statistical parameters from the week 8 primary endpoint with the lower bound of the non-inferiority margin at -3.5 with a 95% confidence interval, the noninferiority margin was met at week 12, indicating that the two study arms are not different at this timepoint. In the intent-to-treat (ITT) population, NORSE EIGHT demonstrated a mean 5.5 letter improvement in BCVA in the ONS-5010 arm and 6.5 letter improvement in BCVA in the ranibizumab arm. BCVA data across all study timepoints demonstrated an improvement in vision, increasing over time, and the presence of biologic activity. Overall, in NORSE EIGHT, ONS-5010 demonstrated mean visual acuity improvements of +3.3 letters at week 4, +4.2 letters at week 8, and +5.5 letters at week 12. Additionally, the complete NORSE EIGHT data set showed that anatomical response was similar between treatments, with a reduction in central retinal thickness of -123.9 microns for ONS-5010 treated eyes and -127.3 microns for the ranibizumab group, virtually no difference between the arms. Central retinal thickness is a key indicator of effectiveness used by retina specialists in the treatment of wet AMD.

Financial Highlights for the Fiscal First Quarter Ended December 31, 2024

For the fiscal first quarter ended December 31, 2024, Outlook Therapeutics reported net income attributable to common stockholders of $17.4 million, or $0.72 per basic and diluted share, compared to a net loss attributable to common stockholders of $11.2 million, or $0.86 per basic and diluted share, for the same period last year. For the fiscal first quarter ended December 31, 2024, Outlook Therapeutics also reported an adjusted net loss attributable to common stockholders1 of $21.6 million, or $0.89 per basic and diluted share, as compared to an adjusted net loss attributable to common stockholders of $10.1 million, or $0.78 per basic and diluted share, for fiscal first quarter of 2024.

Adjusted net loss attributable to common stockholders for the fiscal first quarter ended December 31, 2024 includes $1.3 million of loss from change in fair value of warrant liability and $40.3 million of gain from change in fair value of convertible promissory notes. Adjusted net loss attributable to common stockholders includes $1.0 million of loss from change in fair value of warrant liability and $0.1 million of loss from change in fair value of convertible promissory notes for the fiscal first quarter ended December 31, 2023.

1 Adjusted net loss attributable to common stockholders and adjusted net loss attributable to common stockholders per share of common stock – basic and diluted are non-U.S. GAAP financial measures. See "Non-GAAP Financial Measures" below.

In January 2025, Outlook Therapeutics received $17.8 million in gross proceeds from its previously announced warrant exercise inducement with certain holders of existing warrants to purchase the Company’s common stock. As of December 31, 2024, Outlook Therapeutics had cash and cash equivalents of $5.7 million, excluding the proceeds received from the warrant exercise inducement in January 2025.

About ONS-5010 / LYTENAVA (bevacizumab-vikg, bevacizumab gamma)

ONS-5010 / LYTENAVA is an ophthalmic formulation of bevacizumab for the treatment of wet AMD. LYTENAVA (bevacizumab gamma) is the subject of a centralized Marketing Authorization granted by the European Commission in the European Union (EU) and Marketing Authorization granted by the Medicines and Healthcare products Regulatory Agency (MHRA) in the United Kingdom (UK) for the treatment of wet AMD.

In the United States, ONS-5010 / LYTENAVA (bevacizumab-vikg) is investigational.

Bevacizumab-vikg (bevacizumab gamma in the EU and UK) is a recombinant humanized monoclonal antibody (mAb) that selectively binds with high affinity to all isoforms of human vascular endothelial growth factor (VEGF) and neutralizes VEGF’s biologic activity through a steric blocking of the binding of VEGF to its receptors Flt-1 (VEGFR-1) and KDR (VEGFR-2) on the surface of endothelial cells. Following intravitreal injection, the binding of bevacizumab to VEGF prevents the interaction of VEGF with its receptors on the surface of endothelial cells, reducing endothelial cell proliferation, vascular leakage, and new blood vessel formation in the retina.

On February 14, 2025 UroGen Pharma Ltd. (Nasdaq: URGN), a biotech company dedicated to developing and commercializing innovative solutions that treat urothelial and specialty cancers, reported results from the subgroup analyses of the pivotal ENVISION study evaluating the impact of tumor burden and focality on the response to UGN-102, an investigational drug in development for treatment of LG-IR-NMIBC (Press release, UroGen Pharma, FEB 14, 2025, View Source [SID1234650288]). Analyses of pre-specified subgroups showed comparable CR rates and DOR patterns across different levels of tumor burden (defined as the sum of the diameters of all visible tumors) and number of tumors at baseline in patients treated with UGN-102. The poster presentation titled, Impact of Tumor Burden or Focality in Recurrent Low-Grade Intermediate-Risk Non-Muscle-Invasive Bladder Cancer on Response to Treatment with UGN-102: A Substudy of the Phase 3 ENVISION Trial was presented today at ASCO (Free ASCO Whitepaper) GU 2025.

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"In this subgroup analysis on tumor burden and focality from the ENVISION study, the overall CR rate was consistent, and a majority of patients maintained their response 12 months after achieving CR at three months," said Sandip M. Prasad, M.D., Director of Urology at Morristown Medical Center and lead author of the study. "These results provide evidence of UGN-102’s potential to become an effective and durable treatment option for patients with recurrent LG-IR-NMIBC, regardless of tumor size or focality."

The ENVISION study included 240 patients with recurrent LG-IR-NMIBC who received at least one dose of UGN-102 and 95% (228 patients) received all six weekly intravesical instillations of UGN-102. In this pre-specified analysis CR rates were 82.8% for patients with a tumor burden ≤3 cm (n=149/180) compared to 73.2% for those with a tumor burden >3 cm (n=30/41). Of the patients with CR at three months, 15.4% vs 20.0% experienced recurrence of low-grade disease, progression (either in stage or grade), or death (unrelated to treatment) by 15 months. In the 191 patients with multiple vs single tumors who achieved a CR, the three-month CR was 79.3% vs 82.9%, with recurrence rates of 18.5% vs 11.8%.

"We are encouraged by these results, which highlight the potential of UGN-102 to provide durable responses in patients with recurrent LG-IR-NMIBC," said Mark Schoenberg, M.D., Chief Medical Officer of UroGen. "These pre-specified subgroup analyses further strengthen the growing body of evidence supporting UGN-102 as a treatment option for patients dealing with the challenges of disease recurrence and the need for repeated surgeries."

The ENVISION trial’s primary efficacy and safety results, previously presented, showed that UGN-102 delivered a 79.6% CR rate at three months, with an unprecedented 82.3% probability of remaining in response 12 months later by Kaplan-Meier estimates.

These findings further support UGN-102’s potential to alter the treatment landscape for patients with LG-IR-NMIBC, a condition where recurrence and progression remain significant clinical challenges.

UroGen initiated the submission of a rolling new drug application (NDA) to the U.S. Food and Drug Administration (FDA) for UGN-102 as a treatment for LG-IR-NMIBC in January 2024 and completed the NDA submission in August, ahead of schedule. The FDA accepted the NDA for UGN-102 with a Prescription Drug User Fee Act (PDUFA) goal date of June 13, 2025.

The most common treatment-emergent adverse events (TEAEs) in the ENVISION trial were dysuria, hematuria, urinary tract infection, pollakiuria, fatigue, and urinary retention. The TEAEs were typically mild-to-moderate in severity and either resolved or were resolving. The ENVISION trial demonstrated a similar safety profile to that observed in other studies of UGN-102.

Study limitations include the small sample size of the comparator groups and the single arm design.

The analysis in another presentation titled, Treatment of Low-Grade Intermediate-Risk Non-Muscle-Invasive Bladder Cancer with UGN-102: Results of the Phase 3 ATLAS and ENVISION Studies highlights that in both studies, the CR rate in patients initially treated with UGN-102 was robust, with the majority of patients remaining event-free at 12 months after a three-month CR. A new analysis from the ATLAS trial highlights 54% decreased risk of recurrence, progression or death with UGN-102 compared to TURBT. The hazard ratio for DOR in ATLAS was 0.46 with a 95% confidence interval (0.24, 0.86) favoring the UGN-102 arm. Median DOR was not estimable in any arm due to low recurrence rates; the most common adverse event with UGN-102 in both studies was dysuria, occurring in 22.5% in ENVISION and 30.4% in ATLAS.

About UGN-102

UGN-102 (mitomycin) for intravesical solution is an innovative drug formulation of mitomycin, currently in Phase 3 development for the treatment of LG-IR-NMIBC. Utilizing UroGen’s proprietary RTGel technology, a sustained release, hydrogel-based formulation, UGN-102 is designed to enable longer exposure of bladder tissue to mitomycin, thereby enabling the treatment of tumors by non-surgical means. UGN-102 is delivered to patients using a standard urinary catheter in an outpatient setting by a trained healthcare professional. UroGen completed the NDA submission in August, ahead of schedule. The FDA accepted the NDA for UGN-102 and assigned a PDUFA goal date of June 13, 2025.

About Non-Muscle Invasive Bladder Cancer (NMIBC)

In the U.S., bladder cancer is the second most common urologic cancer in men. LG-IR-NMIBC represents approximately 23,000 newly diagnosed bladder cancer patients each year and an estimated 59,000 recurrences annually among patients diagnosed in previous years. Bladder cancer primarily affects older populations with increased risk of comorbidities, with the median age of diagnosis being 73 years. Guideline recommendations for the management of NMIBC include trans-urethral resection of bladder tumor (TURBT) as the standard of care. Up to 70 percent of NMIBC patients experience at least one recurrence and LG-IR-NMIBC patients are even more likely to recur and face repeated TURBT procedures.

About ENVISION

The Phase 3 ENVISION trial is a single-arm, multinational, multicenter study evaluating the efficacy and safety of UGN-102 (mitomycin) for intravesical solution as a chemoablative therapy in patients with LG-IR-NMIBC. The Phase 3 ENVISION trial completed target enrollment with approximately 240 patients across 56 sites. Study participants received six once-weekly intravesical instillations of UGN-102. The primary endpoint evaluated the CR rate at the three-month assessment after the first instillation, and the key secondary endpoint evaluated durability over time in patients who achieved a CR at the three-month assessment. Learn more about the Phase 3 ENVISION trial at www.clinicaltrials.gov (NCT05243550).