On March 27, 2025 Tempest Therapeutics, Inc. (Nasdaq: TPST), a clinical-stage biotechnology company developing first-in-class1 targeted and immune-mediated therapeutics to fight cancer, reported financial results for the year ended 2024 and provided a corporate update (Press release, Tempest Therapeutics, MAR 27, 2025, View Source [SID1234651540]).

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!

"2024 was another year filled with significant progress and milestone achievements that position Tempest for a successful future," said Stephen Brady, president and chief executive officer of Tempest. "Despite challenging capital markets, our lean team excelled, reporting key OS data from the ongoing randomized Phase 2 trial of amezalpat in first-line hepatocellular carcinoma. As previously announced, we have secured broad regulatory agreement with both the FDA and EMA on the Phase 3 plan and received both Orphan Drug and Fast Track designations from the FDA. We also advanced our second clinical program, TPST-1495, with a Phase 2 clinical trial for the treatment of patients with FAP, with data expected in 2026. Our focus remains on execution with excellence while securing the resources necessary to drive these promising drug candidates forward."

2024 & Recent Accomplishments

Amezalpat (TPST-1120) (clinical PPARα antagonist):

Granted both Orphan Drug and Fast Track designations by the U.S. Food and Drug Administration (FDA) for amezalpat for the treatment of patients with HCC.
Received a "Study May Proceed" letter from the FDA to evaluate amezalpat in combination with atezolizumab (TECENTRIQ) and bevacizumab (Avastin), the current standard of care for unresectable or metastatic HCC, in a pivotal Phase 3 trial for the first-line treatment of unresectable or metastatic HCC.
Announced an agreement with F. Hoffmann-La Roche Ltd. (Roche) to advance the evaluation of amezalpat in combination with atezolizumab and bevacizumab into a pivotal Phase 3 trial for the first-line treatment of unresectable or metastatic HCC.
Announced positive feedback from the end-of-Phase 2 meeting with the FDA for amezalpat in combination with atezolizumab and bevacizumab to treat first-line unresectable or metastatic HCC.
Reported new positive survival data from the ongoing global randomized Phase 1b/2 clinical study demonstrating that amezalpat delivered a six-month improvement in median overall survival (OS) when combined with atezolizumab and bevacizumab in comparison to atezolizumab and bevacizumab alone, the standard of care, in the first-line treatment of patients with unresectable or metastatic HCC.
Published positive data from Phase 1 trial of amezalpat in patients with advanced solid tumors in the Journal of Cancer Research Communications. Data showed that amezalpat demonstrated clinical activity, including tumor shrinkage, even in PD-1 inhibitor-refractory and immune-compromised cancers. These data complement the positive Phase 1b/2 data reported in October 2023 and June 2024 from a global randomized study of amezalpat in combination with atezolizumab and bevacizumab in first-line patients with advanced HCC.
Reported new preclinical data at the 2024 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting demonstrating that amezalpat reduces kidney cancer growth as a monotherapy, while also showing increased inhibition when combined with frontline chemotherapy and immunotherapy. These data further support the clinical benefit observed in the amezalpat Phase 1 data presented in an oral presentation at ASCO (Free ASCO Whitepaper) 2022.
TPST-1495 (clinical dual EP2/4 prostaglandin receptor antagonist)
Received a "Study May Proceed" letter from the FDA to evaluate TPST-1495 in a Phase 2 Trial for the treatment of FAP.
Corporate:
Expanded leadership team to strengthen global clinical expertise with the appointments of Troy M. Wagner as Vice President of Quality Assurance and Sheldon Mullins as Vice President of Regulatory Affairs.
Potential Future Milestones

Amezalpat (TPST-1120) (clinical PPARα antagonist)
Plan to advance amezalpat into a registrational study in first-line liver cancer patients, subject to obtaining additional resources.
TPST-1495 (clinical dual EP2/4 prostaglandin receptor antagonist)
Plan to advance TPST-1495 into a Phase 2 study in patients with FAP under the auspices of the Cancer Prevention Clinical Trials Network and funded by the National Cancer Institute (NCI) Division of Cancer Prevention in 2025, with data expected in 2026.
Financial Results

Year End 2024

Tempest ended the year with $30.3 million in cash and cash equivalents, compared to $39.2 million on December 31, 2023. The decrease was primarily due to cash used in operating activities, offset by proceeds from the issuance of common stock of $28.6 million from the at-the-market offering program.
Net loss and net loss per share for the year were $41.8 million and $1.50, respectively, compared to $29.5 million and $1.91, respectively, for the same period in 2023.
Research and development expenses for the year were $28.5 million compared to $17.5 million for the same period in 2023. The $11.0 million increase was primarily due to an increase in costs incurred from engaging contract research and manufacturing organizations in preparation for our pivotal Phase 3 trial of amezalpat for the treatment of first-line HCC.
General and administrative expenses for the year were $13.6 million compared to $11.7 million for the same period in 2023. The $1.9 million increase was primarily due to an increase in stock-based compensation expense due to increased headcount as well as an increase in expenses related to legal and consulting services.

On March 27, 2025 Shattuck Labs, Inc. (Shattuck) (NASDAQ: STTK), a biotechnology company pioneering the development of novel therapeutics targeting tumor necrosis factor (TNF) superfamily receptors for the treatment of patients with inflammatory and immune-mediated diseases, reported financial results for the fourth quarter and full year ended December 31, 2024 and provided recent business highlights (Press release, Shattuck Labs, MAR 27, 2025, View Source [SID1234651539]).

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!

"Shattuck made the difficult but appropriate decision to terminate our SL-172154 program in 2024, and rapidly transitioned to our potential first-in-class DR3 blocking antibody, SL-325," said Taylor Schreiber, M.D., Ph.D., Chief Executive Officer of Shattuck. "In February, we presented preclinical results from our IND-enabling GLP toxicology study for SL-325 at ECCO, demonstrating differentiation from TL1A blocking monoclonal antibodies, along with a favorable safety profile, full receptor occupancy, and lack of DR3 agonism. Our encouraging preclinical data underscore SL-325’s potential for DR3 blockade to provide potentially best-in-class clinical remission rates for IBD patients. We are on track for an IND filing in the third quarter of this year and are excited to begin generating data with the first-ever DR3 blocking antibody to enter clinical trials. Shattuck remains well-positioned to fund operations and clinical development of SL-325 into 2027."

DR3 Program Development in 2025

•Shattuck’s lead product candidate, SL-325, is a potentially first-in-class DR3 antagonist antibody. SL-325 is a DR3 blocking antibody for the treatment of IBD and other inflammatory and immune-mediated diseases.
◦IND filing expected in the third quarter of 2025.
◦Phase 1 clinical trial will evaluate safety, tolerability, and pharmacokinetics, and determine the recommended Phase 2 dose and dosing schedule of SL-325, with complete enrollment expected in the second quarter of 2026.
•Shattuck continues to develop multiple preclinical DR3-based bispecific antibodies, which are designed to inhibit both the DR3/TL1A axis and another biologically relevant target for the treatment of patients with IBD. Shattuck plans to nominate a lead bispecific candidate from its preclinical pipeline in 2025.

Fourth Quarter 2024 Business Highlights and Other Recent Developments

DR3 Program Development
•Shattuck Labs participated in an oral presentation at ECCO in February 2025.
◦Preclinical studies of SL-325 in NHP demonstrated a favorable safety profile with no infusion-related reactions observed, no changes in clinical pathology parameters, gross pathology, or histopathology analysis, and a No Observed Adverse Effect Level determined to be 100mg/kg, the top administered dose;
◦Full receptor occupancy at 1 mg/kg or greater, durable for >28 days, no Treg expansion or activation of CD3 T cells observed; and •Differentiation from TL1A blocking monoclonal antibodies may yield a distinct profile for bispecific antibody development. Notably, by targeting DR3, immune complex formation and stabilization of TL1A is not expected with SL-325, which may improve the immunogenicity profile as compared to TL1A targeting agents and allow for the development of DR3-based bispecific antibodies. Durable blockade of constitutively expressed DR3 may translate to higher complete remission rates.
•Shattuck Labs presented a poster at the 2025 Crohn’s & Colitis Foundation Congress in February.
◦Data from in vitro preclinical development and characterization of SL-325 were presented.
◦SL-325 is a fully Fc-silenced humanized immunoglobulin G monoclonal antibody that demonstrated high affinity binding to human DR3 and potent antagonistic properties with no evidence of residual agonism.
Upcoming Events
•Shattuck plans to attend the following investor conference. Details will be included on the Events & Presentations section of the Company’s website.
◦24th Annual Needham Virtual Healthcare Conference, April 7–10, 2025. Taylor Schreiber, M.D., Ph.D., CEO of Shattuck Labs, will participate in a presentation on April 9, 2025.

Fourth Quarter and Full-Year 2024 Financial Results

•Cash and Cash Equivalents and Investments: As of December 31, 2024, cash and cash equivalents and investments were approximately $73.0 million, as compared to $130.6 million as of December 31, 2023.

•Research and Development (R&D) Expenses: R&D expenses were $15.4 million for the quarter ended December 31, 2024, as compared to $15.2 million for the quarter ended December 31, 2023. R&D expenses for the year ended December 31, 2024 were $67.2 million, as compared to $74.3 million for the year ended December 31, 2023. This decrease for the full year was primarily driven by decreases in manufacturing costs associated with SL-172154 and research expenses associated with other research programs.
•General and Administrative (G&A) Expenses: G&A expenses were $4.2 million for the quarter ended December 31, 2024, as compared to $4.4 million for the quarter ended December 31, 2023. General and administrative expenses for the year ended December 31, 2024 were $19.1 million, as compared to $19.3 million for the year ended December 31, 2023. This decrease for the full year was primarily the result of a decrease in insurance, software, and information technology costs.

•Net Loss: Net loss was $18.7 million for the quarter ended December 31, 2024, or $0.37 per basic and diluted share, as compared to a net loss of $17.7 million for the quarter ended December 31, 2023, or $0.41 per basic and diluted share. Net loss for the year ended December 31, 2024 was $75.4 million, or $1.49 per basic and diluted share, as compared to $87.3 million, or $2.05 per basic and diluted share, for the year ended December 31, 2023.

Financial Guidance

As of December 31, 2024, cash and cash equivalents and investments were approximately $73.0 million. Shattuck’s current cash and cash equivalents are expected to fund operations into 2027. This cash runway guidance is based on the Company’s current operational plans and excludes any additional capital that may be received, proceeds from business development transactions, and/or additional costs associated with clinical development activities that may be undertaken.

About SL-325
SL-325 is a potential first-in-class Death Receptor 3 (DR3) blocking antibody designed to achieve a complete and durable blockade of the clinically validated DR3/TL1A pathway. Shattuck’s preclinical studies demonstrate high affinity binding and superior activity over TL1A antibodies, and offer a data-driven rationale for targeting the TNF receptor, DR3, versus its ligand, TL1A. SL-325 has completed a GLP toxicology study in non-human primates, with an IND filing expected in the third quarter of 2025.

On March 27, 2025 Sensei Biotherapeutics, Inc. (Nasdaq: SNSE), a clinical-stage biotechnology company focused on the discovery and development of next-generation therapeutics for cancer patients, reported initial results from the dose expansion portion of its Phase 1/2 trial evaluating solnerstotug (formerly SNS-101), a conditionally active monoclonal antibody targeting VISTA (V-domain Ig suppressor of T cell activation) (Press release, Sensei Biotherapeutics, MAR 27, 2025, View Source/news-releases/news-release-details/sensei-biotherapeutics-reports-favorable-preliminary-dose" target="_blank" title="View Source/news-releases/news-release-details/sensei-biotherapeutics-reports-favorable-preliminary-dose" rel="nofollow">View Source [SID1234651538]).

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!

"Checkpoint inhibitor resistance remains a significant challenge for patients with advanced cancer, with limited treatment options beyond chemotherapy or clinical trials," said Ron Weitzman, M.D., Chief Medical Officer of Sensei Biotherapeutics. "Historically, patients who progress on PD-(L)1 therapy are estimated to have a ≤5% likelihood of response to PD-(L)1 rechallenge, making this an extremely difficult-to-treat population, and a large unmet medical need. The initial 14% response rate seen with solnerstotug is nearly three times higher than what would typically be expected in this setting. We believe these early data suggest solnerstotug may provide a meaningful clinical benefit in select tumor types, and we look forward to further evaluating its potential in Phase 2."

Phase 1 Dose Expansion Preliminary Results

The Phase 1 dose expansion trial is a multi-center, open-label, dose expansion study evaluating solnerstotug as monotherapy and in combination with Libtayo (cemiplimab), Regeneron’s PD-1 inhibitor, in both a basket of "hot" tumors that typically respond to immunotherapy but have progressed on prior PD-(L)1 therapy and a single "cold" tumor histology (microsatellite stable (MSS) CRC) that is typically unresponsive to immunotherapy.

As of March 17, 2025, the study has enrolled 60 patients, including:

40 patients with "hot" tumors, including Non-Small Cell Lung Cancer (NSCLC), Head and Neck (H&N) cancer, Melanoma, Renal Cell Carcinoma (RCC), Merkel Cell Carcinoma (MCC), MSI-H Colorectal Cancer (CRC), and other tumor types. All patients received the combination of solnerstotug (3 mg/kg or 15 mg/kg) and cemiplimab.
At the time of this data cut, 21 "hot" tumor PD-(L)1 resistant patients were considered evaluable for efficacy, having received at least one post-baseline scan. An additional 11 patients have not yet reached the first baseline scan, and an additional 8 patients discontinued the study prior to any post-baseline scan.
20 patients with PD-(L)1 non-responsive microsatellite stable (MSS) Colorectal Cancer (CRC) were included to assess potential activity in "cold" tumors. Of these patients, 10 were enrolled in a monotherapy (15 mg/kg) cohort and 10 received the combination of solnerstotug (15 mg/kg) and cemiplimab.
17 MSS CRC patients were considered evaluable for efficacy, having received at least one post-baseline scan. Three patients discontinued the study prior to any post-baseline scan.
Key findings include:

14% ORR (3 patients) and 62% DCR (disease control rate) (13 patients) among 21 evaluable PD-(L)1 resistant "hot" tumor patients.
Durable complete response (CR) in a MCC patient treated with 15 mg/kg solnerstotug + cemiplimab. Patient continues on treatment at 42+ weeks. Previously received a PD-(L)1 therapy for 15 months in the adjuvant setting prior to progressing on therapy.
Partial response (PR) at Week 12 in a MCC patient treated with 15 mg/kg solnerstotug + cemiplimab. Patient continues on treatment at 12+ weeks. Previously received several lines of checkpoint therapy, including the combination of PD-1 and CTLA-4, with a best response of stable disease prior to progressing on therapy.
Partial response (PR) at Week 36 in an MSI-H CRC patient treated with 15 mg/kg solnerstotug + cemiplimab. Patient had durable stable disease (SD) through the course of treatment before converting to a PR at Week 36. Patient continues on treatment at 36+ weeks. Previously received a PD-(L)1 therapy for more than 4 years, where the patient achieved a CR prior to progressing on therapy.
Six PD-(L)1 resistant patients with SD remain on treatment past 12+ weeks, with tumor reductions ranging from 0% to 17%, suggesting durable disease control in a subset of patients.
All PD-(L)1 resistant patients on study with tumor shrinkage remain on treatment, suggesting potential for prolonged benefit.
None of the MSS CRC patients experienced a CR or PR, consistent with prior checkpoint therapy in this "cold" tumor type.
Solnerstotug continues to be well tolerated, with no dose-limiting toxicities and the majority of AEs Grade 1 or 2 in severity. Out of 60 patients, there have been four (7%) cases of Grade 1 cytokine release syndrome (CRS), all mild and manageable. Two patients in the combination cohort experienced immune-mediated events.

A Challenging Treatment Landscape for PD-(L)1 Resistant Tumors

Patients who progress following treatment with PD-1 or PD-L1 inhibitors ("secondary resistance") face a particularly poor prognosis, as resistance to immune checkpoint blockade is a significant challenge in oncology. According to the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper), secondary resistance is defined as disease progression following an initial period of disease control. For patients who develop secondary resistance after treatment with PD-(L)1 immune checkpoint inhibitors, the likelihood of benefiting from a rechallenge with the same therapy is estimated to be 5% or less.1 Currently, treatment options for PD-(L)1 resistant tumors are limited, with many patients receiving chemotherapy, experimental therapies in clinical trials, or palliative care in the absence of effective alternatives. Existing immune checkpoint inhibitor (ICI) combination therapies have not been approved in this setting. They are either highly toxic, such as CTLA-4+PD-1 in which up to 40% of patients discontinue due to severe immune-related adverse events (irAEs), or offer limited treatment potential, such as LAG-3+PD-1 where the ORR has been 9-12%.

"While we remain in the early stages of evaluating solnerstotug’s therapeutic potential, the observed responses—particularly in MCC and MSI-H CRC—are encouraging given the historically poor prognosis of these patients once they have progressed on checkpoint therapy," said Dr. Shiraj Sen, M.D., Medical Oncologist and Director of Clinical Research at NEXT Oncology – Dallas, and a Principal Investigator for the solnerstotug study. "Continued clinical evaluation will be key in determining which patients are most likely to benefit from this approach."

Next Steps: Preparing for Phase 2

Subject to raising sufficient capital, Sensei plans to initiate a Phase 2 study in Q1 2026, with the trial design and patient selection strategies to be informed by the ongoing dose expansion results. Further analyses, including biomarker-based patient selection, are underway to optimize the Phase 2 design.

Investor Webcast Information

Sensei will host an investor webcast today at 5:30 p.m. ET, featuring company leadership and Dr. Shiraj Sen, M.D., Ph.D., Medical Oncologist and Director of Clinical Research at NEXT Oncology-Dallas, an investigator in the Phase 1/2 study.

Access the live event here: View Source

A replay will be available after the webcast on the Investor Relations page of Sensei’s website: View Source

On March 27, 2025 REGiMMUNE Limited, a biotech company focused on the regulatory T cell targeting drugs for immunotherapy, reported the termination of its potential merger with Kiji Therapeutics (Press release, REGimmune, MAR 27, 2025, View Source [SID1234651537]). This decision was made after thorough discussions and mutual agreement, considering strategic adjustments and business objectives.

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!

Kenzo Kosuda, CEO of REGiMMUNE stated: "We appreciated Kiji’s cooperation and shared achievements throughout this potential merger. While this chapter closes, we remain open to other potential collaborations in the future."

On March 27, 2025 Rakovina Therapeutics Inc. (TSX-V: RKV) (FSE: 7JO), a biopharmaceutical company advancing innovative cancer therapies through artificial intelligence (AI)-powered drug discovery, reported that two of its abstracts have been accepted for presentation at the upcoming 2025 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, taking place April 25-30 in Chicago, Illinois (Press release, Rakovina Therapeutics, MAR 27, 2025, View Source;utm_medium=rss&utm_campaign=rakovina-therapeutics-unveils-preclinical-data-at-the-aacr-worlds-premier-cancer-research-forum [SID1234651536]).

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 AACR (Free AACR Whitepaper) Annual Meeting is widely considered the most prestigious global forum for cancer research. It is where the world’s leading scientists, clinicians, and biotech innovators gather to unveil next-generation oncology breakthroughs. Rakovina’s acceptance to present, highlights growing recognition for its pioneering work at the intersection of AI technology and precision cancer therapy.

AI-Designed Therapies Poised to Transform Cancer Treatment

Rakovina will present two abstracts at the meeting, the first: Discovery of novel PARP1-selective inhibitors for treatment of brain tumors using artificial intelligence, explores the use of artificial intelligence (AI) to develop a novel, brain-penetrant, PARP1-selective inhibitor for treating brain tumors. Current PARP inhibitors face challenges such as poor blood-brain barrier (BBB) permeability and off-target effects due to PARP2 inhibition. By leveraging Deep Docking, a deep learning-based virtual screening method, alongside generative AI algorithms, researchers rapidly identified potential compounds with strong PARP1 selectivity and BBB penetration. The study presents findings from in silico screening of billions of compounds, followed by in vitro and in vivo validation of their efficacy, selectivity, and pharmacokinetic properties. This AI-driven approach enhances the efficiency of drug discovery, offering a promising new treatment option for brain tumors.

The second abstract: Utilizing artificial intelligence for the discovery of a novel CNS-penetrating ATR inhibitor, highlights the use of artificial intelligence (AI) to develop a novel CNS-penetrating ATR inhibitor for treating brain tumors. ATR plays a key role in DNA damage repair, and while ATR inhibitors show therapeutic potential, current options have poor blood-brain barrier (BBB) permeability, limiting their effectiveness against brain tumors and metastases. The Enki platform, an AI-driven approach utilizing generative models and deep learning, was employed to design de novo molecules with optimized potency, selectivity, and BBB penetration. Preliminary results include AI-generated ATR inhibitors validated for target specificity, metabolic stability, and permeability.

"This is an exceptional accomplishment for Rakovina," said Jeffrey Bacha, Executive Chairman of Rakovina Therapeutics. "Being selected by AACR (Free AACR Whitepaper) for two projects highlights the significance of our innovations in drug discovery and their potential to impact patients battling aggressive, treatment-resistant cancers."

The company’s proprietary integration of Deep Docking and Enki AI platforms allows its scientists to evaluate billions of potential compounds at 100x the speed of traditional methods, with 6,000x greater enrichment of viable candidates. These innovations are further supported by Rakovina’s access to the University of British Columbia’s state-of-the-art wet lab infrastructure, enabling rapid in-house testing and optimization.

"What we’re seeing with Rakovina’s AI-enabled pipeline is the future of oncology—faster, smarter, and more precise," said Dr. Mads Daugaard, President and CSO of Rakovina "This integration of generative AI and biological insight is transforming how—and how quickly—we can identify and advance new therapies."

With a world-class team, including the creator of Deep Docking and a former AstraZeneca DDR program director, Rakovina is driving innovation in a space projected to reach $18 billion annually by 2030. The company’s preclinical pipeline is focused on therapies that target DNA-repair vulnerabilities present in up to 75% of solid tumors, with an emphasis on hard-to-treat cancers such as breast, ovarian, prostate, and brain.