On February 25, 2025 ORIC Pharmaceuticals, Inc. (Nasdaq: ORIC), a clinical stage oncology company focused on developing treatments that address mechanisms of therapeutic resistance, reported focused registrational clinical development plans for its two lead programs, an extension of projected cash runway into 2027 (from previous guidance of late 2026), and accelerated/augmented corporate milestones (Press release, ORIC Pharmaceuticals, FEB 25, 2025, View Source [SID1234650544]).

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"Based on the initial data we have generated with ORIC-944 and ORIC-114 and recent clinical data reported with other programs in mCRPC and NSCLC, we have refined our registrational plans to focus on the most promising opportunities for both programs," stated Jacob M. Chacko, M.D., president and chief executive officer. "For ORIC-944, based on both internal and external data that validate the combination of PRC2 inhibitors with AR inhibitors in mCRPC, we intend to initiate our first Phase 3 trial in 1H 2026. For ORIC-114, we intend to initiate registrational trial(s) in 2026 with a focus on areas of highest unmet need in first-line NSCLC settings. With these focused registrational plans, we have extended our projected cash runway into 2027."

Registrational Clinical Development Plans and Updated Corporate Milestones:

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

Given the recently reported encouraging early safety and efficacy data from an ongoing dose escalation trial for ORIC-944 in combination with apalutamide in patients with metastatic castration resistant prostate cancer (mCRPC) and favorable enrollment trends, ORIC now expects to report dose escalation data of ORIC-944 both in combination with apalutamide and in combination with darolutamide in 1H 2025, followed by an additional update in 2H 2025.
Expected timing for the previously communicated milestone of ORIC-944 dose optimization data in combination with AR inhibitor(s) has been accelerated/narrowed to 4Q25 or 1Q26 (previously 4Q25 or 1H 2026).
ORIC expects to initiate its first Phase 3 trial for ORIC-944 in mCRPC in 1H 2026.
ORIC-114: a brain penetrant, orally bioavailable, irreversible EGFR/HER2 inhibitor

Given favorable enrollment for ORIC-114 in the 1L EGFR exon 20 monotherapy cohort and the 2L+ atypical EGFR cohort, ORIC now expects to provide a comprehensive data update during 2H 2025 that will include these two cohorts along with cohorts for 2L EGFR exon 20 and 2L+ HER2 exon 20.
ORIC-114 in combination with subcutaneous (SC) amivantamab in patients with 1L EGFR exon 20 has recently been initiated. Initial data from this trial in addition to ORIC-114 data as a monotherapy in 1L EGFR atypical mutations are expected in mid-2026.
ORIC expects to initiate Phase 3 trial(s) for ORIC-114 in 1L NSCLC in 2026, in EGFR exon 20, HER2 exon 20, and/or atypical EGFR mutations. ORIC does not currently plan to pursue registrational trials of ORIC-114 in 2L EGFR and 2L+ HER2 exon 20 NSCLC given the more significant commercial opportunity in first-line settings and the current state of capital markets.
Corporate Highlights:

Cash, cash equivalents and investments totaled $256 million as of December 31, 2024; based on the refined operating plan, projected cash runway has been extended into 2027.

On February 25, 2025 Aktis Oncology, an oncology company focused on unlocking the breakthrough potential of targeted radiopharmaceuticals for large patient populations not addressed by existing platform technologies, reported that Matthew Roden, Ph.D., President and Chief Executive Officer of Aktis Oncology, will participate in investor meetings at the 45th Annual TD Cowen Health Care Conference in Boston, Mass. on Tuesday, March 4, 2025 (Press release, Aktis Oncology, FEB 25, 2025, View Source [SID1234650562]).

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On February 24, 2025 Cellectis (the "Company") (Euronext Growth: ALCLS – NASDAQ: CLLS), a clinical-stage biotechnology company using its pioneering gene-editing platform to develop life-saving cell and gene therapies, reported an innovative strategy for T cell engineering that leverages the pro-inflammatory properties of interleukin 2 (IL-2) with the objective to enhance CAR T cell efficacy against solid tumors, at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) – Immuno-oncology (AACR-IO), taking place on February 23-26, 2025 in Los Angeles, CA (Press release, Cellectis, FEB 24, 2025, View Source [SID1234650466]).

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The data are presented in a poster:

CAR induced expression of synthetically engineered FAP-IL2v immunocytokine boosts persistent anti-tumor activity of TALEN-edited allogeneic CAR T-cells without associated IL-2 toxicity

Presenter: Shipra Das, Ph.D., Associate Director Immuno-Oncology, at Cellectis.

Date/Time: February 25, 2025, 1:45-4:45 p.m. PT

Session: Poster Session B

CAR T-cell therapies have transformed the treatment landscape for specific hematological malignancies and have shown promising preliminary efficacy in solid tumors.
Recent studies suggest a link between the in vivo expansion and persistence of CAR-T cells and enhanced therapeutic outcomes in patients. The co-administration of interleukin-2 (IL-2) has been demonstrated to improve CAR T-cell engraftment, expansion, and functionality in preclinical models but poses toxicity risks at high doses.
Using Cellectis’ TALEN gene editing technology, we developed ‘Smart CAR T cells’ with the ability to express a CAR-inducible IL-2 variant (IL-2v) immunocytokine, potentiated by tumor-specific cues for localized activity within the solid tumor microenvironment (TME).
CAR-inducible expression of this recombinant FAPscFv-IL2v boosts anti-tumor activity of engineered CAR T-cells both in vitro and in vivo. Notably, the enhancement of CAR T-cell activity mediated by IL-2v relies on its anchoring to the FAP protein, which is uniquely present in the TME, thus minimizing the systemic toxicity typically associated with circulating free IL-2 cytokines.
This proposed cellular engineering strategy would represent an effective and safe method to substantially improve CAR T cell expansion and anti-tumor activity, while confining IL-2 activity to the tumor microenvironment.

On February 24, 2025 Veracyte, Inc. (Nasdaq: VCYT) reported financial results for the fourth quarter and full year ended December 31, 2024 (Press release, Veracyte, FEB 24, 2025, View Source [SID1234650483]).

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"I’m incredibly proud of what our team accomplished in 2024," said Marc Stapley, Veracyte’s chief executive officer. "We ended the year with exceptional performance, delivering record revenue in Q4 and achieving our 10th consecutive quarter of 20% or greater testing revenue growth. Looking ahead to 2025, we see significant opportunities for Decipher and Afirma to impact more patients and drive growth for Veracyte. We are focused on moving forward with our exciting portfolio of strategic growth drivers while maintaining the financial discipline that has been core to our success."

Key Fourth Quarter 2024 Financial Highlights

For the three-month period ended December 31, 2024, as compared to the same period in 2023:

Increased total revenue by 21% to $118.6 million and testing revenue by 24% to $112.2 million.
Increased total volume by 22% to 41,271 tests and testing volume by 25% to 39,107 tests.
Grew Decipher revenue by 44% and Afirma revenue by 4%.
Grew Decipher volume by 45% to more than 22,400 tests and Afirma volume by 8% to more than 16,300 tests.
Increased net income to $5.1 million, or 4.3% of revenue, and delivered adjusted EBITDA of $26.1 million, or 22.0% of revenue.
Generated $24.5 million of cash from operations.
Key Full Year 2024 Financial Highlights

For the twelve-month period ended December 31, 2024, as compared to the same period in 2023:

Increased total revenue by 23% to $445.8 million and testing revenue by 28% to $419.0 million.
Increased total volume by 20% to 152,750 tests and testing volume by 23% to 142,925 tests.
Grew Decipher revenue by 43% and Afirma revenue by 14%.
Grew Decipher volume by 36% to more than 80,000 tests and Afirma volume by 12% to more than 60,000 tests.
Increased net income to $24.1 million, or 5.4% of revenue, and delivered adjusted EBITDA of $91.9 million, or 20.6% of revenue.
Generated $75.1 million of cash from operations to end the year with $289.4 million of cash, cash equivalents and short-term investments.
Key Business Highlights

Through Level I evidence for the 22-Gene Genomic Classifier (GC) (Decipher), secured its position as the only gene expression test included in V1.2025 of the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Prostate Cancer published in December 2024.1
Received approval from Molecular Diagnostic Services Program (MolDx) for the technical assessment submission for Decipher for use in the metastatic population.
Announced 17 Decipher-focused abstracts to be presented at the 2025 ASCO (Free ASCO Whitepaper) GU Symposium demonstrating the power of the Veracyte diagnostics platform and Veracyte’s commitment to continued leadership in supporting clinical research around urologic cancers.
Published our 2024 Environmental, Social and Governance Report.
1

NCCN = National Comprehensive Cancer Network (NCCN). Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Prostate Cancer v.1.2025. © National Comprehensive Cancer Network, Inc. 2024. All rights reserved. Accessed February 12, 2025. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.

Fourth Quarter 2024 Financial Results

Total revenue for the fourth quarter of 2024 was $118.6 million, an increase of 21% compared to $98.2 million reported in the fourth quarter of 2023. Testing revenue was $112.2 million, an increase of 24% compared to $90.4 million in the fourth quarter of 2023, driven by the strong performance of our Decipher and Afirma tests. Product revenue was $3.0 million, a decrease of 18% compared to $3.7 million in the fourth quarter of 2023. Biopharmaceutical and other revenue was $3.5 million, a decrease of 17% compared to $4.1 million in the fourth quarter of 2023.

Total gross margin for the fourth quarter of 2024 was 66.4%, compared to 66.0% in the fourth quarter of 2023. Non-GAAP gross margin was 69.3%, compared to 70.6% in the fourth quarter of 2023.

Operating expenses were $74.6 million for the fourth quarter of 2024. Non-GAAP operating expenses were $57.9 million, flat compared to $57.9 million in the fourth quarter of 2023.

Net income for the fourth quarter of 2024 was $5.1 million, an improvement of 118% compared to the fourth quarter of 2023, representing 4.3% of revenue compared to (28.8%) in the same period in 2023. Diluted net earnings per common share was $0.06, an improvement of $0.45 compared to the fourth quarter of 2023. Non-GAAP diluted net earnings per common share was $0.36, an improvement of $0.15 compared to the fourth quarter of 2023. Net cash provided by operating activities in the fourth quarter of 2024 was $24.5 million, an improvement of $9.0 million compared to the same period in 2023.

Adjusted EBITDA for the fourth quarter of 2024 was $26.1 million, an improvement of 76% compared to the fourth quarter of 2023, representing 22.0% of revenue compared to 15.1% of revenue in the same period of 2023.

Full Year 2024 Financial Results

Total revenue for 2024 was $445.8 million, an increase of 23% compared to $361.1 million in 2023. Testing revenue was $419.0 million, an increase of 28% compared to $326.5 million in 2023, driven by the strong performance of our Decipher and Afirma tests. Product revenue was $13.7 million, a decrease of 12% compared to $15.6 million in 2023. Biopharmaceutical and other revenue was $13.2 million, a decrease of 30% compared to $18.9 million in 2023.

Total gross margin for the full year 2024 was 66.9%, compared to 63.6% in 2023. Non-GAAP gross margin was 70.0%, compared to 69.3% in 2023.

Operating expenses were $282.0 million for the full year 2024. Non-GAAP operating expenses grew 7% to $227.6 million compared to $212.5 million in 2023.

Net income for the full year 2024 was $24.1 million, an improvement of 132% compared to 2023, representing 5.4% of revenue compared to (20.6%) in 2023. Diluted net earnings per common share was $0.31, an improvement of $1.33 compared to 2023. Non-GAAP diluted net earnings per common share was $1.19, an improvement of $0.61 compared to 2023. Net cash provided by operating activities in 2024 was $75.1 million, an improvement of $30.9 million compared to 2023.

Adjusted EBITDA for the full year 2024 was $91.9 million, an improvement of 102% compared to 2023, representing 20.6% of revenue compared to 12.6% of revenue in 2023.

A reconciliation of GAAP to non-GAAP financial measures has been provided in the tables included in this press release. An explanation of these measures is also included below under the heading "Note Regarding Use of Non-GAAP Financial Measures."

Update on Marseille Operations

Veracyte is evaluating its ownership and operations of the company’s French subsidiary, Veracyte SAS, whose business is located in Marseille, France and includes Veracyte’s immune-oncology biopharma business, contract development and manufacturing, and support for Veracyte’s IVD development and manufacturing. Veracyte recently notified Veracyte SAS that, as sole shareholder of Veracyte SAS, it is considering no longer funding the French entity. Accordingly, Veracyte SAS will engage with its works council, as is required by French law, over the next few months.

Seeking external buyer(s) for a potential divestiture of all or part of the French entity’s activities is an option that is actively being explored. Without Veracyte Inc.’s continued funding or identification of a buyer for all or part of the Veracyte SAS assets, Veracyte SAS may be required to begin bankruptcy proceedings following its works council consultation period.

Management will provide further details on this process and its potential impact on Veracyte’s 2025 financial outlook during the conference call this afternoon.

2025 Financial Outlook

The company expects 2025 testing revenue to be in the range of $470 million to $480 million, or 12% to 15% year-over-year growth. Adjusting for the impact of the paused Envisia test, the guidance implies testing revenue growth of 14% to 16%. Given the number of variables impacting its Marseille, France operations, the company is not providing total company revenue guidance at this time and expects to provide its total revenue outlook for 2025 once there is more clarity on the timing and impact of the process underway.

The company also expects adjusted EBITDA as a percentage of revenue in 2025 to be approximately 21.6% compared to 20.6% in 2024.

The company is unable to provide a quantitative reconciliation of expected adjusted EBITDA as a percentage of revenue to the most directly comparable forward-looking GAAP measure, without unreasonable effort, because of the inherent difficulty in accurately forecasting the occurrence and financial impact of the various adjusting items necessary for such reconciliations that have not yet occurred, that are dependent on various factors, are out of the company’s control, or that cannot be reasonably predicted. Such adjustments include, but are not limited to, acquisition related expenses, and other adjustments. Any associated estimate of these items and their impact on GAAP performance for the guidance period could vary materially. For more information on the non-GAAP financial measures, please refer to the section titled "Note Regarding Use of Non-GAAP Financial Measures" at the end of this press release.

Conference Call and Webcast Details

Veracyte will host a conference call and webcast today at 4:30 p.m. Eastern Time to discuss the company’s financial results and provide a general business update. The conference call will be webcast live from the company’s website and will be available via the following link: View Source The webcast should be accessed 10 minutes prior to the conference call start time. A replay of the webcast will be available for one year following the conclusion of the live broadcast and will be accessible on the company’s website at View Source

On February 24, 2025 Synnovation Therapeutics, a precision medicine company focused on the discovery and development of best-in-class targeted medicines, reported that the first patient has been dosed in a Phase I trial evaluating SNV4818 as a monotherapy and in combination with fulvestrant, in patients with breast cancer and other solid tumors (Press release, Synnovation Therapeutics, FEB 24, 2025, View Source [SID1234650499]). SNV4818 is a potentially best-in-class pan-mutant-selective PI3Kα inhibitor that may effectively cover kinase (H), helical domain (E), and other PI3Kα mutations clinically. This marks the second Synnovation program to enter the clinic in just over three years since company formation. Synnovation’s lead candidate and potentially best-in-class PARP1 selective program, SNV1521, entered a Phase I trial in January of 2024.

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The SNV4818 Phase I trial, which is being led by Timothy Yap, M.D., Ph.D., Professor of Investigational Cancer Therapeutics at the University of Texas MD Anderson Cancer Center, is designed to evaluate the safety, tolerability and preliminary efficacy of SNV4818 as a monotherapy in tumor agnostic patients with PI3Kα activating mutations as well as in combination with fulvestrant in HR+/HER2- advanced breast cancer patients.

"We are excited to initiate the clinical development of our second potential best-in-class program, both of which were discovered at Synnovation," said Kevin O’Hayer, M.D., Ph.D., Senior Vice President, Head of Clinical Development at Synnovation. "SNV4818 has the potential to address a significant unmet need for a large population of patients with breast cancer and multiple other tumor types."

The potential of the PI3Kα inhibitor class has been limited by a lack of selectivity against wild type PI3Kα. First generation PI3Kα-isoform specific inhibitors are limited by significant toxicities due to wild type PI3Kα inhibition, including stomatitis, hyperglycemia and rash. A pan-mutant selective, wild-type-sparing, inhibitor enables a wider therapeutic index leading to greater target inhibition which may improve clinical efficacy while decreasing toxicity, unlocking significant potential for this therapeutic class.

SNV4818 is a potentially best-in-class, highly potent pan-mutant PI3Kα inhibitor with excellent selectivity against wild type PI3Kα. This selectivity may allow for broad spectrum PI3Kα mutation coverage including targeting both H1047X and E545/542X classes of driver mutations in breast cancer and other solid tumor indications.