On February 26, 2025 Sonnet BioTherapeutics Holdings, Inc. (the "Company" or "Sonnet") (NASDAQ: SONN), a clinical-stage company developing targeted immunotherapeutic drugs, reported the presentation of a compilation of data at the 2025 American Association for Cancer Research (AACR) (Free AACR Whitepaper) IO Conference (Press release, Sonnet BioTherapeutics, FEB 26, 2025, View Source [SID1234650641]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

As part of the conference, Dr. Sant Chawla, Principal Investigator at the Sarcoma Oncology Center in Santa Monica, California, presented a poster entitled, "Combination immunotherapy with an albumin-binding interleukin-12 fusion protein that extends cytokine half-life, targets the tumor microenvironment, and enhances therapeutic efficacy." This is the first time the overall strategy of Sonnet’s Fully Human Albumin Binding (FHAB) platform has been compiled with existing data and presented in a poster. The presented poster is now available on the Publications page of the Company’s website.

SON-1010 is the Company’s proprietary version of recombinant human interleukin-12 (rhIL-12), configured using genetic fusion to the FHAB platform, which extends the half-life and bioactivity of the IL-12 component due to binding native albumin in the serum. Albumin binding to FcRn, GP60, and SPARC results in an improved PK profile, decreased toxicity risk, and a broader therapeutic index preclinically, with significant targeting of the tumor microenvironment and increases in activated NK, NKT, Th1, and cytotoxic CD8 T cells, as well as marked repolarization of pro-tumor M2 MDSCs to inflammatory M1 APCs.

"Recombinant interleukins have generally had limited clinical success due to inefficient tumor targeting, short half-lives, and off-target toxicity. As previously disclosed, our novel FHAB platform has demonstrated the potential for us to design product candidates that safely extend the half-life of cytokines and deliver them to the tumor, where they can convert the immunological response from ‘cold’ to ‘hot’ and potentially realize the promise of immunotherapy. We are pleased to share the compilation of data in this poster presentation and look forward to announcing additional data from our ongoing studies evaluating our SON-1010 platform in 2025," commented Pankaj Mohan, Ph.D., Founder and Chief Executive Officer of Sonnet.

Key Highlights:

● A platform strategy was developed that links cytokines to the FHAB as mono- or bifunctional fusions to bind native albumin at both physiologic and acidic pH, taking advantage of albumin’s long serum half-life and concentration in tumors, allowing delivery to and accumulation of the drug in the TME. IL-12 is a potent cytokine that stimulates the innate and adaptive immune responses, functioning in combination with other cytokines, like IL-15 and IL-18. Several approaches are currently being studied in humans, such as:

○ SON-1010 monotherapy at the highest dose is continuing in patients with advanced solid tumors. In December 2024, the Company disclosed clinical benefit in 48% of patients, including a partial response at the highest dose in a patient with clear cell sarcoma. The poster reflects the current status of this trial.

○ Co-administration with a checkpoint inhibitor (atezolizumab) to activate local immune cells and upregulate PD-L1 in the TME. Safety has been monitored at each dose escalation step and the most common adverse events at each dose level have been updated for the results currently available.

○ SON-1010 is being administered alternating with an immunoreactive chemotherapy drug (trabectedin) to enhance its ability to activate a pro-inflammatory phenotype in the TME.

○ Alternating administration with a potent chemotherapeutic regimen (NALIRIFOX) will be done in front-line patients with pancreatic ductal adenocarcinoma (PDAC) to enhance their response.

● Each setting has the potential to augment the effects of the licensed therapy in populations that continue to have high unmet needs for an improved outcome. Immunotherapy allows greater flexibility in selecting potentially synergistic combinations for rational implementation.

● SON-1010 and SON-1210 address paramount safety and tolerability factors, which have traditionally hindered the use of therapeutic cytokines in the treatment of solid tumors, by extending the cytokine half-life and improving the therapeutic index that may result in better patient outcomes.

SON-1010 is being evaluated in a Phase 1b/2a dose-escalation and proof-of-concept study (SB221) in combination with SON-1010 and atezolizumab (Tecentriq) (in collaboration with Genentech, a member of the Roche Group), which is focused on platinum-resistant ovarian cancer (PROC) (NCT05756907). The extended PK of SON-1010, along with its ability to induce IFNγ in the TME causing upregulation of PD-L1, creates an opportunity for synergistic activity. Enrollment remains ongoing and an update on safety at the MTD in that trial is expected in Q1 calendar year 2025. Another trial evaluating dose escalation of SON-1210 (IL12-FHAB-IL15), followed by its combination with NALIRIFOX in patients with metastatic pancreatic cancer, is expected to begin later this calendar year.

About SON-1010

SON-1010 is a candidate immunotherapeutic recombinant drug that links unmodified single-chain human IL-12 with the albumin-binding domain of the single-chain antibody fragment A10m3. This single-chain antibody fragment was selected to bind albumin both at normal pH, as well as at the acidic pH typically found in the TME. The FHAB technology targets tumor and lymphatic tissue, providing a mechanism for dose sparing and an opportunity to improve the safety and efficacy profile of not only IL-12, but a variety of potent immunomodulators that can be linked using the platform. Interleukin-12 can orchestrate a robust immune response to many cancers and pathogens. Given the types of proteins induced in the TME, such as the Secreted Protein and Rich in Cysteine (SPARC) and glycoprotein 60 (GP60), several types of cancer, such as non-small cell lung cancer, melanoma, head and neck cancer, sarcoma, and some gynecological cancers are particularly relevant to this approach. SON-1010 is designed to deliver IL-12 to local tumor tissue, turning ‘cold’ tumors ‘hot’ by stimulating IFNγ, which activates innate and adaptive immune cell responses and increases the production of Programed Death Ligand 1 (PD-L1) on tumor cells.

On February 26, 2025 Schrödinger, Inc. (Nasdaq: SDGR) reported financial results for the fourth quarter and full-year ended December 31, 2024, and provided its financial outlook for 2025 (Press release, Schrodinger, FEB 26, 2025, View Source [SID1234650640]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"We are delighted with Schrödinger’s excellent financial performance in 2024. Software revenue growth exceeded our expectations, showing the resilience of our business through changing industry cycles and the impact of large contract renewals. Our drug discovery collaboration portfolio is expanding, driven by our new agreement with Novartis and expanded collaborations with Otsuka and Lilly, and we expect to report initial clinical data from our three lead proprietary programs this year," said Ramy Farid, Ph.D., chief executive officer of Schrödinger. "We continue to see increasing momentum and conviction around our validated computational methods and are committed to remaining scientific leaders in this area. With our platform, our collaborations, our programs, and our strong financial position, we believe we are well positioned to deliver across all facets of our business in 2025 and beyond."

Today Schrödinger also announced that it has expanded its research collaboration with Eli Lilly and Company. This expansion builds on the companies’ previously announced collaboration, with the addition of an undisclosed target. The terms of the expanded collaboration are consistent with the previously announced agreement.

Fourth Quarter 2024 Financial Results
•Total revenue for the fourth quarter increased 19.1% to $88.3 million, compared to $74.1 million in the fourth quarter of 2023.
•Software revenue for the fourth quarter increased 16.0% to $79.7 million, compared to $68.7 million in the fourth quarter of 2023. The increase was primarily due to increased hosted revenue from large customers with additional contribution from new multi-year customer agreements.
•Drug discovery revenue was $8.7 million for the fourth quarter, compared to $5.5 million in the fourth quarter of 2023. The increase was primarily due to the recognition of milestones during the quarter.
•Software gross margin decreased to 83% for the fourth quarter, compared to 87% in the fourth quarter of 2023, primarily reflecting higher cost of revenue associated with the predictive toxicology initiative.
•Operating expenses were $84.8 million for the fourth quarter, compared to $87.2 million for the fourth quarter of 2023.
•Other expense, which includes changes in fair value of equity investments and interest income/expense, was $18.5 million for the fourth quarter, compared to $1.9 million for the fourth quarter of 2023.
•Net loss for the fourth quarter was $40.2 million, compared to $30.7 million in the fourth quarter of 2023.

Three Months Ended
December 31,
2024 2023 % Change
(in millions)
Total revenue $ 88.3 $ 74.1 19%
Software revenue 79.7 68.7 16%
Drug discovery revenue 8.7 5.5 58%
Software gross margin 83 % 87 %
Operating expenses $ 84.8 $ 87.2 (2.7)%
Other expense $ (18.5) $ (1.9) —
Net loss $ (40.2) $ (30.7) —

Full Year 2024 Financial Results
•Total revenue for the full year decreased 4.2% to $207.5 million, compared to $216.7 million for 2023.
•Software revenue for the full year increased 13.3% to $180.4 million, compared to $159.1 million for 2023. Revenue growth was primarily driven by increases in hosted contracts and contribution revenue.
•Drug discovery revenue for the full year was $27.2 million compared to $57.5 million for 2023. The first quarter of 2023 included the recognition of a $25 million milestone from BMS.
•Software gross margin was 80% for the full year, compared to 81% for 2023.
•Operating expenses were $341.4 million for the full year, compared to $318.1 million for 2023, primarily due to higher research and development expenses.
•Other income, which includes gains/loss on equity investments, changes in fair value of such investments and interest income/expense, was $23.6 million for the full year, compared to $220.4 million for 2023.
•Net loss for the full year was $187.1 million, compared to income of $40.7 million for 2023.
•At December 31, 2024, Schrödinger had cash, cash equivalents, restricted cash and marketable securities of approximately $367.5 million, compared to approximately $398.4 million at September 30, 2024 and approximately $468.8 million at December 31, 2023. In January 2025, Schrodinger received the $150 million upfront payment from Novartis for the recently announced drug discovery collaboration.

Twelve Months Ended
December 31,
2024 2023 % Change
(in millions)
Total revenue $ 207.5 $ 216.7 (4.2)%
Software revenue 180.4 159.1 13%
Drug discovery revenue 27.2 57.5 (53)%
Software gross margin 80 % 81 %
Operating expenses $ 341.4 $ 318.1 7.3%
Other income $ 23.6 $ 220.4 —
Net (loss) income $ (187.1) $ 40.7 —

For the three months and year ended December 31, 2024, Schrödinger reported net losses of $40.2 million and $187.1 million, respectively, compared to a net loss of $30.7 million and net income of $40.7 million for the three months and year ended December 31, 2023, respectively.
For the three months and year ended December 31, 2024, Schrödinger reported non-GAAP net losses of $17.2 million and $191.4 million, respectively, compared to non-GAAP net losses of $23.0 million and $157.8 million

for the three months and year ended December 31, 2023, respectively. See "Non-GAAP Information" below and the table at the end of this press release for a reconciliation of non-GAAP net income (loss) to GAAP net income (loss).

Full Year 2024 Key Performance Indicators (KPIs)
Schrödinger today reported 2024 key performance indicators for both the software and drug discovery components of its business.

Software. Total annual contract value (ACV) increased 23.7% to $190.8 million, and the ACV of Top 10 customers increased 43% to $73.1 million. The number of customers with an ACV of at least $5 million increased from four to eight, and the number of customers with an ACV of at least $1 million increased from 27 to 31. Schrödinger’s customer retention rate among customers with an ACV of at least $500,000 was 100% and the number of such customers increased from 54 to 61.

Drug discovery. Schrödinger ended 2024 with 13 ongoing programs eligible for royalties, compared to 12 the previous year. For the year ended December 31, 2024, the number of collaborators since 2018 increased to 19.

Software KPI 2024 2023
Total annual contract value (ACV) $190.8 million $154.2 million
ACV of Top 10 customers $73.1 million $51.0 million
Number of customers with at least $5M in ACV 8 4
Number of customers with at least $1M in ACV 31 27
Number of customers with at least $500,000 in ACV 61 54
Number of customers with at least $100,000 in ACV 235 222
Customer retention rate with at least $500,000 in ACV 100% 98%
Customer retention with at least $100,000 in ACV 95% 92%
Number of active customers with ACV of at least $1,000 1,752 1,785

Drug Discovery KPI 2024 2023
Ongoing programs eligible for royalties 13 12
Number of collaborators since 2018 19 17

For additional information about the company’s KPIs, see "Operating Metrics" below.

2025 Financial Outlook
As of February 26, 2025, Schrödinger provided the following expectations for the fiscal year ending December 31, 2025:
•Software revenue growth is expected to range from 10% to 15%.
•Drug discovery revenue is expected to range from $45 million to $50 million.
•Software gross margin is expected to range from 74% to 75%.
•Operating expense growth in 2025 is expected to be less than 5%.
•Cash used for operating activities in 2025 is expected to be significantly lower than cash used for operating activities in 2024.

For the first quarter of 2025, software revenue is expected to range from $44 million to $48 million.

Key Highlights
Collaborative Pipeline & Co-Founded Companies
•Earlier today, the company announced an expanded research collaboration with Lilly. The expansion adds an undisclosed target to the companies’ previously announced collaboration under terms consistent with the existing agreement.

•In January, Schrödinger announced that its research collaboration with Novartis received antitrust regulatory clearance, and Schrödinger received the upfront payment of $150 million from Novartis in January 2025.

•Also in January, the company announced an expanded research collaboration agreement with Otsuka Pharmaceutical Co., Ltd. The expansion adds another undisclosed target to the collaboration under terms consistent with the existing agreement.
•In December, Ajax Therapeutics, a company co-founded by Schrödinger, presented an overview poster of its ongoing Phase 1 trial evaluating AJ1-11095 for the treatment of myelofibrosis at the 66th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition.

•Also in December, Structure Therapeutics, a company co-founded by Schrödinger, announced the selection of ACCG-2671, as its lead oral small molecule amylin receptor agonist for the treatment of obesity. Schrödinger collaborated with Structure on the discovery of ACCG-2671 and is entitled to milestones and low single-digit royalties on sales.

Proprietary Pipeline
•In January, the U.S. Food and Drug administration granted SGR-2921, the company’s CDC7 inhibitor, Orphan Drug Designation for the treatment of acute myeloid leukemia (AML). Schrödinger expects to present initial clinical data from the ongoing Phase 1 study of SGR-2921 in patients with AML and myelodysplastic syndrome (MDS) in the second half of 2025.

•Schrödinger continues to progress the Phase 1 clinical study of SGR-1505, the company’s MALT1 inhibitor, in patients with relapsed/refractory B-cell malignancies and expects to report initial clinical data from the trial in the second quarter of 2025.

•The Phase 1 study of SGR-3515, Schrödinger’s Wee1/Myt1 inhibitor, continues to enroll patients with advanced solid tumors at sites in the U.S. and Canada. Initial clinical data from this study is expected in the second half of 2025.

Platform
•The company is continuing to advance the science underpinning its platform, including advancing its predictive toxicology initiative, further integrating physics and AI/ML into platform workflows, and expanding the applicability of the platform to new high-value areas, including biologics and drug formulations.

•In January, Schrödinger scientists published a paper assessing the accuracy of free-energy perturbation (FEP) in predicting relative binding energies of ligands to DNA and RNA targets. The assessment suggests FEP+ has sufficient accuracy to guide lead optimization in drug discovery programs targeting nucleic acids.

Webcast and Conference Call Information
Schrödinger will host a conference call to discuss its fourth quarter and full year 2024 financial results on Wednesday, February 26, 2025, at 4:30 p.m. ET. The live webcast can be accessed under "News & Events" in the investors section of Schrödinger’s website, View Source To participate in the live call, please register for the call here. It is recommended that participants register at least 15 minutes in advance of the call. Once registered, participants will receive the dial-in information. The archived webcast will be available on Schrödinger’s website for approximately 90 days following the event.

On February 26, 2025 Revolution Medicines, Inc. (Nasdaq: RVMD), a late-stage clinical oncology company developing targeted therapies for patients with RAS-addicted cancers, reported its financial results for the quarter and full year ended December 31, 2024, and provided an update on corporate progress (Press release, Revolution Medicines, FEB 26, 2025, View Source [SID1234650639]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The company’s mission is to revolutionize treatment for patients with RAS-addicted cancers through the discovery, development and delivery of innovative, targeted medicines across lines of therapy and tumor types. Its deep pipeline of clinical-stage RAS(ON) inhibitors includes daraxonrasib (RMC-6236), a RAS(ON) multi-selective inhibitor; elironrasib (RMC-6291), a RAS(ON) G12C-selective inhibitor; and zoldonrasib (RMC-9805), a RAS(ON) G12D-selective inhibitor.

"In 2024 we built on our record of execution by advancing our highly differentiated portfolio of RAS-focused investigational drugs, making significant progress in building the organizational capabilities needed to drive the next stage of our strategy, and ending the year in an exceptionally strong financial position," said Mark A. Goldsmith, M.D., Ph.D., chief executive officer and chairman of Revolution Medicines. "In 2025 we aim to increase impact for patients with RAS-addicted tumors, including pancreatic cancer and lung cancer, by enrolling the ongoing registrational trials and opening additional pivotal trials in earlier lines of therapy."

Recent Clinical Highlights

Pancreatic Ductal Adenocarcinoma (PDAC)

The company currently has two RAS(ON) inhibitors being developed for patients with PDAC, daraxonrasib and zoldonrasib. The company is evaluating these compounds as monotherapy and in combination regimens.

Daraxonrasib in PDAC

On December 2, 2024, the company reported a new analysis of safety and activity data from its ongoing monotherapy trial of daraxonrasib in patients with previously treated PDAC harboring a RAS mutation. As of the July 23, 2024 data cutoff date, at the 300 mg once daily (QD) dose, the same dose used in the ongoing RASolute 302 Phase 3 PDAC trial, patients with PDAC harboring a KRAS G12X mutation achieved a median progression-free survival (PFS) of 8.8 months (95% confidence interval (CI), 8.5 – not estimable (NE)), while the median overall survival (OS) was not estimable (95% CI, NE – NE), and patients with PDAC harboring any RAS mutation achieved a median PFS of 8.5 months (95% CI, 5.9 – NE), while the median OS was not estimable (95% CI, 8.5 – NE).

These data are consistent with the initial dataset from the same July 23, 2024 data cutoff date presented at the EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) (Triple) meeting in October 2024, which demonstrated that, at a dose range of 160 to 300 mg QD, patients with PDAC harboring a KRAS G12X mutation achieved a median PFS of 8.5 months (95% CI, 5.3 – 11.7) and a median OS of 14.5 months (95% CI, 8.8 – NE), while patients with PDAC harboring any RAS mutation achieved a median PFS of 7.6 months (95% CI, 5.9 – 11.1) and a median OS of 14.5 months (95% CI, 8.8 – NE).

Daraxonrasib exhibited a manageable safety and tolerability profile in both datasets and no new safety signals were observed. The most common treatment-related adverse events (TRAEs) were rash and gastrointestinal-related toxicities that were primarily Grade 1 or 2 in severity. No Grade 3 or higher TRAEs were observed in greater than 10% of patients and there were no treatment discontinuations due to TRAEs.

On January 24, 2025, at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Gastrointestinal Cancers Symposium (ASCO GI), the company presented data showing that treatment with daraxonrasib induced early and deep reduction of RAS mutant circulating tumor DNA (ctDNA) in patients with previously treated PDAC, indicating inhibition of all major forms of oncogenic RAS. These results further support the ongoing RASolute 302 trial.

Zoldonrasib in PDAC

On October 25, 2024, the company reported first-in-human clinical results for zoldonrasib at the Triple meeting. Zoldonrasib demonstrated encouraging safety and antitumor activity in patients with RAS G12D PDAC.

Non-Small Cell Lung Cancer (NSCLC)

The company is also developing its RAS(ON) inhibitors for patients with advanced NSCLC.

Daraxonrasib in NSCLC

On December 2, 2024, the company reported updated results in patients with previously treated RAS mutant NSCLC who received daraxonrasib. Daraxonrasib was generally well tolerated and demonstrated favorable dose intensity and compelling PFS and OS.

Supported by these data, and having finalized the study design disclosed on December 2, 2024, the company has initiated a global, randomized Phase 3 trial (RASolve 301) of daraxonrasib versus docetaxel in patients with previously treated, locally advanced or metastatic NSCLC.

RAS(ON) Inhibitor Combination Trials

The company has ongoing efforts to identify and advance rational combination strategies with its RAS(ON) inhibitors, using a data-driven approach to prioritize among multiple options for advancing into early lines of therapy.

Daraxonrasib with Pembrolizumab

On December 2, 2024, the company reported data showing that the combination of daraxonrasib with pembrolizumab in NSCLC was generally well tolerated, and the safety profile was consistent with previously reported results for the individual agents.

Elironrasib with Daraxonrasib

On December 2, 2024, the company reported initial clinical safety, tolerability and activity for the first-of-its-kind RAS inhibitor doublet with the combination of elironrasib with daraxonrasib, which showed the combination was generally well tolerated and provided initial proof-of-mechanism in patients with colorectal cancer who were previously treated with a KRAS(OFF) G12C inhibitor. The company believes these preliminary observations support continued development of this RAS(ON) inhibitor doublet in a broad range of G12C-mutant tumor types and earlier lines of therapy.

Elironrasib with Pembrolizumab

On December 2, 2024, the company reported initial safety and tolerability data on the combination of elironrasib with pembrolizumab in patients with RAS G12C-mutant NSCLC, which support combinability with a safety profile consistent with previously reported results for the individual agents.

The company believes the three pairwise combinations of elironrasib with daraxonrasib, daraxonrasib with pembrolizumab, and elironrasib with pembrolizumab justify investigation of the triplet combination of elironrasib and daraxonrasib with pembrolizumab as a potential chemotherapy-sparing, first-line option for patients with NSCLC.

Zoldonrasib with Daraxonrasib

The company has completed dose escalation for a second RAS(ON) inhibitor doublet – zoldonrasib combined with daraxonrasib – and is currently in an expansion phase across a range of solid tumors at the anticipated single agent recommended Phase 2 doses for both agents.

Strategic Priorities and Markers of Progress

The company has five strategic priorities for this year to maximize the potential impact for patients with RAS-addicted cancers:

Execute pivotal trials with daraxonrasib monotherapy in patients with previously treated metastatic PDAC and NSCLC.

The company anticipates substantially completing enrollment in RASolute 302, the company’s randomized Phase 3 trial comparing daraxonrasib to standard of care chemotherapy in 2L patients with metastatic PDAC, in 2025 to enable an expected data readout in 2026.

Having finalized the study design disclosed on December 2, 2024, the company is now activating investigational sites for RASolve 301, its global randomized Phase 3 trial comparing daraxonrasib to docetaxel in patients with previously treated, locally advanced or metastatic RAS mutant NSCLC.

Advance daraxonrasib into earlier-line randomized pivotal trials in patients with PDAC.

The company anticipates initiating two pivotal trials in earlier lines of treatment for PDAC in the second half of 2025:

• A global, randomized Phase 3 trial in first-line patients with metastatic PDAC. The trial is expected to compare a reference arm of patients treated with chemotherapy to two investigational arms, one with patients treated with daraxonrasib monotherapy and one with patients treated with daraxonrasib plus chemotherapy.

• A global, randomized Phase 3 trial of daraxonrasib as adjuvant treatment for patients with resectable PDAC.

Generate sufficient data to inform development priorities for the mutant-selective inhibitors elironrasib and zoldonrasib and prepare to initiate one or more pivotal trials either as monotherapy or in a drug combination.

The company expects to share additional clinical safety and antitumor activity on zoldonrasib in the second quarter of 2025.

The company currently expects to initiate one or more pivotal combination trials in 2026 that incorporate either elironrasib or zoldonrasib and expects to share clinical data supporting these plans in the second or third quarter of 2025.

Progress earlier-stage pipeline, including advancing next-generation innovations from the company’s highly productive discovery organization.

The company expects to advance RMC-5127, a RAS(ON) G12V-selective inhibitor, to a clinic-ready stage in 2025 to enable the expected initiation of a first-in-human dose escalation Phase 1 clinical trial in 2026.

Grow commercial and operational capabilities and increase pre-commercial activities in support of a potential launch.

The company continues to expand key aspects of its organization to support a potential launch by continuing to add top talent, including U.S. field teams. The company plans to retain control of U.S. commercial rights as a core element of the current strategy and is also exploring strategies for serving patients outside the U.S., potentially including partnership opportunities.
Corporate and Financial Highlights

Financing

In December 2024, the company completed an upsized public equity offering, raising $823 million in net proceeds. This included the exercise in full by the underwriters of their option to purchase additional shares of common stock. These funds will be used to strengthen the company’s balance sheet and overall financial position to support the continued development and expansion of its product pipeline and preparation for the potential commercial launch of daraxonrasib, subject to FDA approval.

Fourth Quarter Results

Cash Position: Cash, cash equivalents and marketable securities were $2.3 billion as of December 31, 2024, compared to $1.9 billion as of December 31, 2023. The increase was primarily attributable to the company’s public equity offering in December 2024.

R&D Expenses: Research and development expenses were $188.1 million for the quarter ended December 31, 2024, compared to $148.5 million for the quarter ended December 31, 2023. The increase was primarily due to an increase in clinical trial expenses for daraxonrasib, elironrasib, and zoldonrasib, and an increase in personnel-related expenses related to additional headcount. Research and development expenses for the quarter ended December 31, 2023, included $13.1 million of expenses related to the wind-down of EQRx, Inc. (EQRx), which primarily consisted of non-recurring employee-related termination expenses and stock-based compensation expense related to the acceleration of EQRx equity awards in conjunction with the closing of the transaction.

G&A Expenses: General and administrative expenses were $28.2 million for the quarter ended December 31, 2024, compared to $32.2 million for the quarter ended December 31, 2023. The decrease was primarily due to $13.8 million of expenses related to the wind-down of EQRx, which primarily consisted of non-recurring employee-related termination expenses and stock-based compensation expense related to the acceleration of EQRx equity awards in conjunction with the closing of the EQRx transaction that were included in the quarter ended December 31, 2023, offset by an increase in commercial preparation activities and an increase in personnel-related expenses related to additional headcount.

Net Loss: Net loss was $194.6 million for the quarter ended December 31, 2024, compared to net loss of $161.5 million for the quarter ended December 31, 2023. Net loss for the quarter ended December 31, 2023, included $26.9 million of operating expenses related to the wind-down of EQRx.

Full Year 2024 Financial Highlights

Revenue: Total revenue was zero for the year ended December 31, 2024, compared to $11.6 million for the year ended December 31, 2023. The decrease in revenue was due to the termination of the company’s collaboration agreement with Sanofi in 2023.

R&D Expenses: Research and development expenses were $592.2 million for the year ended December 31, 2024, compared to $423.1 million for the year ended December 31, 2023. The increase was primarily due to an increase in clinical trial expenses for daraxonrasib, elironrasib and zoldonrasib, an increase in personnel-related expenses related to additional headcount, and an increase in stock-based compensation. Research and development expenses for the year ended December 31, 2023, included $13.1 million of expenses related to the wind-down of EQRx.

G&A Expenses: General and administrative expenses were $97.3 million for the year ended December 31, 2024, compared to $75.6 million for the year ended December 31, 2023. The increase was primarily due to an increase in commercial preparation activities and an increase in personnel-related expenses related to additional headcount. General and administrative expenses for the year ended December 31, 2023, included $13.8 million of expenses related to the wind-down of EQRx.

Net Loss: Net loss was $600.1 million for the year ended December 31, 2024, compared to net loss of $436.4 million for the year ended December 31, 2023.

2025 Financial Guidance
Revolution Medicines expects full year 2025 GAAP net loss to be between $840 million and $900 million, which includes estimated non-cash stock-based compensation expense of between $115 million and $130 million. Based on the company’s current operating plan, the company projects that current cash, cash equivalents and marketable securities can fund planned operations into the second half of 2027.

Webcast
Revolution Medicines will host a webcast this afternoon, February 26, 2025, at 4:30 p.m. Eastern Time (1:30 p.m. Pacific Time). To listen to the live webcast, or access the archived webcast, please visit: View Source Following the live webcast, a replay will be available on the company’s website for at least 14 days.

On February 26, 2025 Relay Therapeutics, Inc. (Nasdaq: RLAY), a clinical-stage precision medicine company transforming the drug discovery process by combining leading-edge computational and experimental technologies, reported fourth quarter and full year 2024 financial results and corporate highlights (Press release, Relay Therapeutics, FEB 26, 2025, View Source [SID1234650638]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"Our RLY-2608 breast cancer program continued to advance and develop rapidly in 2024, driven by positive maturation of the RLY-2608 + fulvestrant doublet dataset, now with over 100 patients dosed and median PFS of 11.4 months in second-line patients. We also continue to make progress with our investigational triplet combinations, which we believe could potentially allow RLY-2608 to address patients in earlier settings," said Sanjiv Patel, M.D., President and Chief Executive Officer of Relay Therapeutics. "Looking forward into 2025, it is our top priority to continue advancing our clinical programs, including the initiation of the RLY-2608 + fulvestrant Phase 3 trial in breast cancer patients. With a strong capital position that supports the execution of that pivotal trial, and a team with proven development experience, I am confident in our abilities to meaningfully advance these programs towards patients in oncology and genetic disease areas."

Initiation of ReDiscover-2 Phase 3 trial of RLY-2608 + Fulvestrant in the Middle of 2025

•
Relay Tx has conducted an end of Phase 2 meeting with the Food and Drug Administration (FDA) and announces the Phase 3 trial design, dose, and plans to initiate the trial in mid-2025
•
Design
o
Planned Phase 3 registrational study (ReDiscover-2) is a randomized, open-label, multicenter clinical trial that will evaluate the safety and efficacy of RLY-2608 + fulvestrant in PI3Kα-mutated, HR+/HER2- advanced breast cancer patients previously treated with a CDK4/6 inhibitor
o
Comparator arm will be capivasertib + fulvestrant
o
Key inclusion criteria include:
▪
Patients must be CDK4/6-experienced (either in the adjuvant or metastatic setting)
▪
Patients must have been on frontline endocrine therapy containing regimen for >6 months
▪
Patients may have seen up to 1 prior chemotherapy and no ADC in the metastatic setting

▪
Metabolic inclusion criteria: HbA1c <7% and fasting plasma glucose <140 mg/dL at baseline
o
Target enrollment is 540 patients
o
The primary endpoint is progression free survival (PFS), per RECIST 1.1 criteria, tested hierarchically in patients with PI3Kα mutations in the kinase domain only and in patients with any PI3Kα mutation (kinase + non-kinase mutations)
o
Overall survival is a key secondary endpoint with overall response rate (ORR), duration of response and quality of life as additional secondary endpoints
•
Dose
o
Phase 3 dose of RLY-2608 is 400mg twice daily (BID) in the fed state (fed)
o
A positive food effect has been observed when RLY-2608 was administered to patients in the fed state, which increased the exposure level of RLY-2608 compared to the fasted state (fasted)
o
The RLY-2608 400mg BID fed dose has been shown to achieve exposures equivalent to 600mg BID fasted in cancer patients.
▪
600mg BID fasted was the dose used in our expansion cohorts

Additional Corporate Highlights

•
RLY-2608:
o
RLY-2608 doublet: Presented interim clinical data from the open-label Phase 1b study for RLY-2608 + fulvestrant at the San Antonio Breast Cancer Symposium (SABCS) 2024, showing:
▪
11.4-month median PFS in second line (2L) patients with PI3Kα-mutated, HR+/HER2- advanced breast cancer
▪
39% confirmed ORR across patients with measurable disease (n= 31)
▪
67% Clinical Benefit Rate (CBR) across all evaluable patients (32 of 48 CBR-evaluable patients; CBR defined as the proportion of patients with complete response, partial response or stable disease for at least 24 weeks)
▪
Safety profile (n= 118) remained differentiated with mostly low-grade treatment- related adverse events
o
RLY-2608 triplet: Continued to advance two potential front-line triplet regimens in patients with PI3Kα- mutated, HR+, HER2- advanced breast cancer who had previously received at least one prior CDK4/6 inhibitor, including:
▪
Initiation of triplet cohort for RLY-2608 + fulvestrant + atirmociclib (Pfizer’s selective CDK4 inhibitor) combination
▪
Continued advancement of the ongoing RLY-2608 + fulvestrant + ribociclib combination cohort
o
Planning underway for development of next-generation endocrine therapy combinations with RLY-2608
•
Lirafugratinib:
o
Entered exclusive global licensing agreement, granting Elevar Therapeutics worldwide rights to develop and commercialize lirafugratinib
•
NRAS program:
o
Nominated development candidate, RLY-8161
•
Research:
o
Continued to consolidate and focus the research platform and portfolio on a small number of high-value targets

Anticipated 2025 Milestones

•
RLY-2608 in Breast Cancer:
o
Initiation of Phase 3 trial in the middle of 2025
o
Additional Phase 1b doublet data in 2025

•
Vascular malformations: RLY-2608 clinical trial initiation in the first quarter of 2025
•
NRAS and Fabry programs continue to advance towards IND and timing of clinical start for each program will be phased to optimize resources to ensure the execution of the ReDiscover-2 Phase 3 trial

Fourth Quarter and Full Year 2024 Financial Results

Cash, Cash Equivalents and Investments: As of December 31, 2024, cash, cash equivalents, and investments totaled $781.3 million compared to approximately $750.1 million as of December 31, 2023. The company expects its current cash, cash equivalents and investments will be sufficient to fund its current operating plan into the second half of 2027.

Revenue: There was no revenue for the fourth quarters of 2024 and 2023. Revenue was $10.0 million for the full year 2024, as compared to $25.5 million for the full year 2023. The decrease was primarily due to the timing of milestones achieved, as well as revenue recognized thereon, under the company’s Collaboration and License Agreement with Genentech, Inc.

R&D Expenses: Research and development expenses were $68.1 million for the fourth quarter of 2024, as compared to $77.5 million for the fourth quarter of 2023. Research and development expenses were $319.1 million for the full year 2024, as compared to $330.0 million for the full year 2023. The decreases were primarily due to the impact of prioritization of certain programs in the company’s pipeline, as previously disclosed.

G&A Expenses: General and administrative expenses were $16.9 million for the fourth quarter of 2024, as compared to $16.8 million for the fourth quarter of 2023. General and administrative expenses were $76.6 million for the full year 2024, as compared to $75.0 million for the full year 2023.

Net Loss: Net loss was $76.0 million for the fourth quarter of 2024, or a net loss per share of $0.45, as compared to a net loss of $83.5 million for the fourth quarter of 2023, or a net loss per share of $0.67. Net loss was $337.7 million for the full year 2024, or a net loss per share of $2.36, as compared to a net loss of $342.0 million for the full year 2023, or a net loss per share of $2.79.

On February 26, 2025 Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) reported that the U.S. Food and Drug Administration (FDA) has accepted for review the resubmission of the Biologics License Application (BLA) for odronextamab in relapsed/refractory (R/R) follicular lymphoma (FL) after two or more lines of systemic therapy (Press release, Regeneron, FEB 26, 2025, View Source [SID1234650637]). The target action date for the FDA decision is July 30, 2025 .

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Acceptance of the BLA resubmission follows the achievement of an FDA-mandated enrollment target for the Phase 3 confirmatory trial in R/R FL ( OLYMPIA -1). This was the sole approvability issue identified by the FDA in the complete response letter associated with the previous submission. The BLA resubmission is supported by data from the Phase 1 and pivotal Phase 2 trials (ELM-1 and ELM-2), which demonstrated an overall response rate of 80% (n=103), with 74% (n=95) achieving a complete response. Serious adverse events occurred in 67% of patients; those occurring in ≥10% of patients included cytokine release syndrome, COVID-19 and pneumonia.

Odronextamab is approved as Ordspono in the European Union for the treatment of R/R FL or diffuse large B-cell lymphoma (DLBCL) after two or more lines of systemic therapy although its safety and efficacy have not been fully evaluated by any other regulatory authority. For complete product information, please see the Summary of Product Characteristics that can be found on www.ema.europa.eu.

About FL
FL is one of the most common subtypes of B-cell non-Hodgkin lymphoma (B-NHL). While FL is a slow-growing subtype, it is an incurable disease, and most patients will relapse after initial treatment. It is estimated that approximately 122,000 FL cases are diagnosed globally every year with more than 13,600 FL cases anticipated in the U.S. in 2025.

About the Odronextamab Clinical Development Program
Odronextamab is a CD20xCD3 bispecific antibody designed to bridge CD20 on cancer cells with CD3-expressing T cells to facilitate local T-cell activation and cancer-cell killing.

ELM-1 is an ongoing, open-label, multicenter Phase 1 trial to investigate the safety and tolerability of odronextamab in patients with CD20+ B-cell malignancies previously treated with CD20-directed antibody therapy.

ELM-2 is an ongoing, open-label, multicenter Phase 2 trial investigating odronextamab across five independent disease-specific cohorts, including DLBCL, FL, mantle cell lymphoma, marginal zone lymphoma and other subtypes of B-NHL. The primary endpoint is objective response rate according to the Lugano Classification as assessed by independent review committee, and secondary endpoints include complete response, progression-free survival, overall survival and duration of response. The pivotal results in FL were published in the Annals of Oncology.

Odronextamab is being investigated in a broad clinical development program exploring its use as a monotherapy as well as in combination regimens in several types of B-NHLs in earlier lines of therapy. In FL, odronextamab is being evaluated as a monotherapy against rituximab plus standard-of-care chemotherapies in a Phase 3 confirmatory trial ( OLYMPIA -1) and in combination with chemotherapy against rituximab plus standard-of-care chemotherapies in a separate Phase 3 trial ( OLYMPIA -2). For more information on Regeneron’s clinical trials in blood cancer, visit the clinical trials website or contact via [email protected] or +1 844-734-6643.