ORIC® Pharmaceuticals Reports First Quarter 2025 Financial Results and Operational Updates

On May 5, 2025 ORIC Pharmaceuticals, Inc. (Nasdaq: ORIC), a clinical stage oncology company focused on developing treatments that address mechanisms of therapeutic resistance, reported financial results and operational updates for the quarter ended March 31, 2025 (Press release, ORIC Pharmaceuticals, MAY 5, 2025, View Source [SID1234652515]).

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"In the first quarter, we made significant progress across our pipeline, announced focused registrational development plans for our two lead programs, extended our cash runway, and accelerated key corporate milestones," stated Jacob M. Chacko, M.D., president and chief executive officer. "Looking ahead, we expect to share multiple clinical data updates across both programs over the next fifteen months. We remain on track to initiate the first Phase 3 trial of ORIC-944 in mCRPC in the first half of 2026, with registrational development of ORIC-114 in first-line NSCLC expected to begin later that year."

First Quarter 2025 and Other Recent Highlights

ORIC-944: a potent and selective allosteric inhibitor of PRC2

Reported encouraging early safety and efficacy data in ongoing dose escalation trial for ORIC-944 in combination with apalutamide in patients with metastatic castration resistant prostate cancer (mCRPC).
Presented preclinical ORIC-944 data demonstrating synergistic activity and improved progression-free survival (PFS) when combined with androgen receptor pathway inhibitors (ARPIs) in models of prostate cancer at the 2025 AACR (Free AACR Whitepaper) Annual Meeting.
Announced updated program milestones and development plans to initiate first Phase 3 registrational trial for ORIC-944 in mCRPC in 1H 2026.
ORIC-114: a brain penetrant, orally bioavailable, irreversible EGFR/HER2 inhibitor

Announced a clinical trial collaboration and supply agreement with Johnson & Johnson and initiated a trial to evaluate ORIC-114 in combination with subcutaneous (SC) amivantamab for the 1L treatment of patients with non-small cell lung cancer (NSCLC) harboring EGFR exon 20 insertion mutations.
Announced updated program milestones and registrational development plans to focus ORIC-114 in 1L NSCLC and plans to initiate first Phase 3 trial in 2026.
Corporate Highlights:

Extended projected cash runway into 2027 (from previous guidance of late 2026), and accelerated/augmented corporate milestones, based upon favorable enrollment and focused registrational clinical development plans for two lead programs.
Anticipated Program Milestones:

ORIC anticipates the following upcoming milestones:

ORIC-944 (mCRPC):
1H 2025: Combination dose escalation data with AR inhibitors(s)
2H 2025: Updated combination dose escalation data with AR inhibitors(s)
4Q 2025 / 1Q 2026: Combination dose optimization data with AR inhibitor(s)
ORIC-114 (NSCLC):
2H 2025: 1L EGFR exon 20, 2L EGFR exon 20, 2L+ HER2 exon 20 and 2L+ EGFR atypical data
Mid-2026: 1L EGFR exon 20 combination with SC amivantamab and 1L EGFR atypical data
First Quarter 2025 Financial Results

Cash, Cash Equivalents and Investments: Cash, cash equivalents and investments totaled $223.8 million as of March 31, 2025, which is expected to fund the current operating plan into 2027.
R&D Expenses: Research and development (R&D) expenses were $24.6 million for the three months ended March 31, 2025, compared to $22.0 million for the three months ended March 31, 2024, an increase of $2.7 million. The increase was due to a net increase in external expenses related to the advancement of product candidates, as well as higher personnel costs, including additional non-cash stock-based compensation.
G&A Expenses: General and administrative (G&A) expenses were $8.1 million for the three months ended March 31, 2025, compared to $7.0 million for the three months ended March 31, 2024, an increase of $1.0 million. The increase was primarily due to higher personnel costs, including additional non-cash stock-based compensation.

Largest Sarcoma Study to Date with ctDNA Analysis Demonstrates Excellent Performance for Signatera

On May 5, 2025 Natera, Inc. (NASDAQ: NTRA), a global leader in cell-free DNA and precision medicine, reported the results of a study led by Stanford University School of Medicine for the evaluation of Signatera, Natera’s personalized molecular residual disease (MRD) test, in patients with soft tissue and bone sarcomas (Press release, Natera, MAY 5, 2025, View Source [SID1234652531]). Results of the study (Utilizing Circulating Tumor DNA to Monitor Sarcoma Treatment and Recurrence) were presented at the 2025 Society of Surgical Oncology (SSO) Annual Meeting in March.

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With evaluation of approximately 200 patients and more than 2,100 plasma samples across multiple distinct subtypes, this is the largest sarcoma cohort to date using personalized circulating-tumor DNA (ctDNA) monitoring. The study assessed the correlation of Signatera results with imaging, stratified by sarcoma subtype, and followed patients through treatment, disease progression, and surveillance.

Key findings included:

The results demonstrated excellent test performance, with overall sensitivity to recurrence of 89% and specificity of 100%.
In leiomyosarcoma, the most common subtype in the cohort, sensitivity was 93%, with specificity of 100%.
For leiomyosarcoma patients who experienced progression, ctDNA kinetics during subsequent therapy were highly correlated with treatment response (90%).
Sarcomas are a heterogeneous group of rare cancers, with more than 70 distinct histologic subtypes1, making treatment response and recurrence especially difficult to monitor through standard imaging and clinical evaluation. There are approximately 17,000 new cases of sarcoma diagnosed annually in the United States.2

"This data represents a major step forward in understanding how ctDNA monitoring can be applied across a diverse range of sarcoma subtypes," said Beatrice J. Sun, M.D., department of surgery at Stanford University. "With the ability to noninvasively detect disease recurrence and monitor treatment response, Signatera demonstrates the potential to meaningfully improve personalized care for patients with sarcoma."

"This is the most comprehensive dataset to date on ctDNA monitoring in sarcoma, and it shows excellent performance of Signatera in a difficult-to-monitor cancer," said Alexey Aleshin, M.D., corporate chief medical officer and general manager of oncology at Natera. "The heterogeneity of sarcoma demands a personalized approach, and these results support Signatera’s unique ability to track disease status with precision across a broad spectrum of subtypes."

This retrospective real-world study demonstrates the promise of Signatera as a tool to monitor disease recurrence and treatment response. To build on these findings, the team intends to launch a prospective study to further demonstrate Signatera’s clinical utility and explore its role in informing treatment decisions and improving future sarcoma care.

About Signatera

Signatera is a personalized, tumor-informed, molecular residual disease test for patients previously diagnosed with cancer. Custom-built for each individual, Signatera uses circulating tumor DNA to detect and quantify cancer left in the body, identify recurrence earlier than standard of care tools, and help optimize treatment decisions. The test is available for clinical and research use and has coverage by Medicare across a broad range of indications. Signatera has been clinically validated across multiple cancer types and indications, with published evidence in more than 100 peer-reviewed papers.

Termination of a Material Definitive Agreement

On May 5, 2025, IGM Biosciences, Inc. (the "Company") reported to have received a notice of termination of that certain Collaboration and License Agreement (the "Agreement"), dated as of March 28, 2022, by and between the Company and Genzyme Corporation, a corporation organized under the laws of Massachusetts ("Sanofi"), pursuant to which Sanofi has elected to terminate the Agreement, at will, in its entirety (Filing, IGM Biosciences, MAY 5, 2025, View Source [SID1234652744]). The effective date of the termination is thirty (30) days after the date of such notice.

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Under the original terms of the Agreement, the Company had agreed to generate, develop, manufacture and commercialize IgM antibodies directed to six primary targets, three of which were oncology targets and three of which were immunology targets. The parties concluded that conducting further activities under the Agreement was not in the interests of either party.

BioCryst Reports First Quarter 2025 Financial Results and Provides Business Update

On May 5, 2025 BioCryst Pharmaceuticals, Inc. (Nasdaq:BCRX) reported financial results for the first quarter ended March 31, 2025, and provided a corporate update (Press release, BioCryst Pharmaceuticals, MAY 5, 2025, View Source [SID1234652498]).

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"We started 2025 with another quarter of outstanding performance. ORLADEYO revenue growth was driven by moving ORLADEYO patients from free drug to paid at a much faster rate than we expected, resulting in a substantial increase to our annual guidance as we also move closer to peak sales of $1 billion. This increased financial strength accelerates our path to profitability and enables us to start paying down our debt, while continuing to invest in and advance our pipeline," said Jon Stonehouse, president and chief executive officer of BioCryst.

ORLADEYO (berotralstat): Oral, Once-daily Treatment for Prevention of Hereditary Angioedema (HAE) Attacks

ORLADEYO net revenue in the first quarter of 2025 was $134.2 million (+51 percent year-over-year (y-o-y)).

The total percentage of all ORLADEYO patients on paid drug has increased to approximately 84 percent (compared to 73.5 percent at end of 2024), generating higher than expected ORLADEYO revenue that the company expects will continue through the full year.

First quarter prescriptions were strong, above the quarterly average in 2024, and the percentage of U.S. HAE patients who describe a strong preference for an oral prophylaxis therapy increased to 70 percent, up from 50 percent in 2023, in the company’s latest market survey of HAE patients.

Sales from the U.S. contributed 89.5 percent of global ORLADEYO net revenues in the first quarter. The number of patients treated with ORLADEYO outside the U.S. continued to grow in new and existing markets.
"By driving a dramatic increase in the rate of paid ORLADEYO patients through the prescription reauthorization period, on top of continued very strong new patient demand, our team has achieved in four months what we had expected would take three years, getting the rate of paid patients nearly to our long-term goal of 85 percent. As a result, we will capture significantly more revenue opportunity in 2025 and subsequent years and our path to peak sales of $1 billion is even more profitable than we had projected," said Charlie Gayer, chief commercial officer of BioCryst.

Rare Disease Pipeline

The goal with our pipeline is to build on our success with ORLADEYO by bringing additional selected, highly differentiated rare disease products to patients.

The company has submitted a new drug application (NDA) to the U.S. Food and Drug Administration (FDA) to expand the ORLADEYO label to children with HAE aged 2 to 11 using an oral granule formulation. The company also expects to submit regulatory filings in 2025 in global territories, including Europe, Japan and Canada. ORLADEYO would be the first targeted oral prophylactic therapy for children with HAE.

The FDA has cleared the company’s investigational new drug application (IND) which will enable its clinical trial of BCX17725, an investigational KLK5 inhibitor for the treatment of Netherton syndrome, to enroll patients in the United States. This phase 1 trial is also open in Australia. The company expects initial data from the program in 2025.

Netherton syndrome is a serious, rare, lifelong genetic disorder causing disruption of the skin barrier with premature separation of the skin layers, chronic inflammation and vulnerability to serious infections, caused by lack of normal function of a natural inhibitor of KLK5. People with Netherton syndrome often have itchy, red, scaly, inflamed skin, fragile hair, and are more likely to develop severe food allergies, asthma and eczema. Netherton syndrome can be life threatening, especially during infancy when patients are vulnerable to dehydration and recurrent infections. Currently, there are no approved treatments that target the underlying cause of Netherton syndrome. BCX17725 is designed to replace missing functions of the natural KLK5 inhibitor, which could restore the normal skin barrier and result in improved skin function, including protection from severe inflammatory and infectious complications of the disease.

The first clinical trial with suprachoroidal delivery of avoralstat, the company’s investigational plasma kallikrein inhibitor for the treatment of diabetic macular edema (DME), has been granted authorization to proceed in Australia. The company expects initial data from DME patients in 2025.

DME is an important cause of vision loss in diabetes and is due to leakage of fluid from the blood vessels in the retina. While current treatments focus on vascular endothelial growth factor (VEGF) inhibition, DME can develop from other mechanisms, such as the kallikrein-bradykinin pathway. This is supported by observations that many DME patients have an incomplete response to intravitreal anti-VEGF therapies that are administered every four to eight weeks. Avoralstat targets the kallikrein-bradykinin system on the retinal vascular endothelial cells and may result in less vascular leakage and less edema. Avoralstat, delivered to the suprachoroidal space, is designed to provide long-lasting exposure to the retinal vessels, which could result in less frequent injections and a reduced burden on patients and the healthcare system.
"Today we are reporting significant milestones for each of the next three programs in our pipeline, demonstrating our focus on advancing medicines with the potential to provide differentiated outcomes for patients of all ages. As we move closer to delivering an urgently needed oral prophylactic therapy to children with HAE, we are simultaneously progressing two clinical-stage programs in Netherton syndrome and DME towards the first patient data later this year," said Dr. Helen Thackray, chief research and development officer of BioCryst.

First Quarter 2025 Financial Results

For the three months ended March 31, 2025, total revenues were $145.5 million (+$52.7 million y-o-y), compared to $92.8 million in the first quarter of 2024 (+56.8 percent y-o-y). The increase was primarily due to $134.2 million (+$45.3 million y-o-y) in ORLADEYO net revenue in the first quarter of 2025, compared to $88.9 million in ORLADEYO net revenue in the first quarter of 2024 (+51.0 percent y-o-y).

Research and development expenses for the first quarter of 2025 decreased to $37.3 million from $46.5 million in the first quarter of 2024 (-19.8 percent y-o-y), primarily due to decreased expenses driven by the discontinuation and close-out of the Factor D programs, BCX10013 and BCX9930. These reductions were partially offset by an increase in other research, preclinical and development costs, comprised of avoralstat and other early-phase pipeline programs, and a change in general and administrative expense allocations.

Selling, general and administrative expenses for the first quarter of 2025 increased to $82.5 million, compared to $59.5 million in the first quarter of 2024 (+38.7 percent y-o-y). The increase was primarily due to increased commercial investment to support our growing ORLADEYO revenue, our newly launched regions, expanded international operations and global commercial support activities. Additionally, there was an increase to general and administrative expenses, and an offsetting reduction to research and development expenses, due to a change in the general and administrative expense allocations in 2025.

Operating income for the first quarter of 2025 was $21.2 million, compared to an operating loss of $14.5 million for the first quarter of 2024. Non-GAAP operating income, excluding stock-based compensation expense, was $42.6 million for the first quarter of 2025, compared to a non-GAAP operating loss of $0.8 million for the first quarter of 2024.

Interest expense was $23.5 million in the first quarter of 2025, compared to $24.5 million in the first quarter of 2024 (-4.1 percent y-o-y). The decrease was primarily due to a decrease in interest expense associated with the interest accrued under the Pharmakon Loan Agreement.

Net income for the first quarter of 2025 was $32 thousand, or $0.00 per share, compared to a net loss of $35.4 million, or $0.17 per share, for the first quarter of 2024.

Cash, cash equivalents, restricted cash and investments totaled $317.3 million at March 31, 2025, compared to $338.4 million at March 31, 2024. Net cash utilization for the first quarter of 2025 was $25.5 million, which was driven by debt service, royalty payments and one-time first quarter compensation expense.

Early in the second quarter, the company paid down $75 million of the outstanding Pharmakon debt, which will result in approximately $23.5 million in interest savings over the life of the loan.

Financial Outlook for 2025
The company is increasing its outlook for full year 2025 global net ORLADEYO revenue to be between $580 million and $600 million (previously $535 million to $550 million).

The company now expects full year 2025 operating expenses will be $440 million to $450 million (previously $425 million to $435 million). This operating expense outlook does not reflect non-cash stock compensation expense.

The company is accelerating its expectation for sustainable profitability and positive cash flows by a year. The company now expects to deliver net income and positive cash flows for full year 2025 (previously expected both for full year 2026). Positive cash flow refers to the improvement in cash, cash equivalents, restricted cash and investments from year end 2024 to year end 2025, not including the impact of the $75 million Pharmakon prepayment made in April 2025.

Conference Call and Webcast
BioCryst management will host a conference call and webcast at 8:30 a.m. ET today to discuss the financial results and provide a corporate update. The live call may be accessed by dialing 1-844-481-2942 for domestic callers and 1-412-317-1866 for international callers. A live webcast and replay of the call will be available online in the investors section of the company website at www.biocryst.com.

Orna Therapeutics Announces Presentation at the American Society of Gene and Cell Therapy Annual Meeting Supporting its in vivo CAR Therapy Approach in Autoimmune Diseases

On May 5, 2025 Orna Therapeutics, a biotechnology company dedicated to engineering immune cells in vivo to treat autoimmune and oncology diseases, reported an upcoming presentation at the 28th American Society of Gene & Cell Therapy (ASGCT) (Free ASGCT Whitepaper) Annual Meeting being held May 13-17, 2025, in New Orleans, Louisiana (Press release, Orna Therapeutics, MAY 5, 2025, View Source [SID1234652516]). The presentation will highlight data supporting Orna’s in vivo CAR therapy approach in autoimmune diseases.

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"We are excited to present new data at the upcoming ASGCT (Free ASGCT Whitepaper) annual meeting as we advance our panCAR programs towards the clinic," said Joseph Bolen, Ph.D., Chief Executive Officer of Orna Therapeutics. "Our platform, which pairs our circular (oRNA) technology and best-in-class lipid nanoparticle (LNP) delivery has the potential to deliver a pipeline in a product and treat multiple diseases and therapeutic areas. The data to be presented will highlight the ability of our platform to enable sustained pharmacodynamic effects at low doses, durable protein expression, and repeat dosing. We look forward to advancing our CD19 autoimmune panCAR program into the clinic in 2026, followed by our BCMA panCAR program in oncology."

Presentation details are as follows:

Title: In Vivo panCAR Therapy Using Circular RNA for the Treatment of Autoimmune Disease

Speaker: Megan Hoban, Ph.D., panCAR Program Lead, Orna Therapeutics

Date/Time: Thursday, May 15, 2025, 8:00 AM – 9:45 AM CDT

Session Name: Cellular and Gene Therapies for Autoimmune Disease

Location: Room 388-390

By leveraging its leading oRNA technology and potentially best-in-class LNP delivery, Orna’s in vivo CD19 panCAR platform holds the potential to benefit patients across multiple B cell driven autoimmune diseases. New data to be presented at ASGCT (Free ASGCT Whitepaper) will highlight the ability of Orna’s CD19 panCAR platform to generate deep and sustained B cell depletion in non-human primates across multiple doses.