On March 27, 2025 Tyra Biosciences, Inc. (Nasdaq: TYRA), a clinical-stage biotechnology company focused on developing next-generation precision medicines that target large opportunities in Fibroblast Growth Factor Receptor (FGFR) biology, reported financial results for the fourth quarter and full year ended December 31, 2024, and highlighted recent corporate progress (Press release, Tyra Biosciences, MAR 27, 2025, View Source [SID1234651541]).

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"2024 was a momentous year for TYRA and the patient communities we serve, highlighted by the positive interim results from our SURF301 study, which demonstrated a combination of high anti-tumor activity with favorable tolerability results in very sick, heavily pre-treated cancer patients. Importantly, the oncology doses tested in SURF301 are significantly higher than those to be tested in BEACH301, giving us confidence as we advance TYRA-300 in ACH," said Todd Harris, CEO of TYRA. "Our conviction in TYRA-300 has never been stronger and we are working diligently to advance this potential best-in-class agent for multiple high-value indications in oncology and skeletal dysplasia into three Phase 2 studies in NMIBC, ACH and mUC."

Fourth Quarter and Full Year 2024 and Recent Corporate Highlights

TYRA-300

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Advanced Clinical Evaluation of TYRA-300 into Three Phase 2 Studies. During 2024, TYRA progressed TYRA-300, an oral, investigational FGFR3-selective inhibitor, for the treatment of IR NMIBC, mUC and ACH, and achieved the following milestones:
o
Cleared Phase 2 NMIBC IND with US FDA – SURF302. TYRA expanded the clinical development of TYRA-300 into NMIBC to address the unmet needs in this cancer population for an efficacious, orally available therapy. SURF302 is an open-label Phase 2 clinical study evaluating the efficacy and safety of TYRA-300 in participants with FGFR3-altered low-grade, IR NMIBC. The study will enroll up to 90 participants at multiple sites primarily in the United States. Participants will be randomized initially to treatment with TYRA-300 at 50 mg once-daily (QD) (Cohort 1) or treatment with TYRA-300 at 60 mg QD (Cohort 2). Following a review of efficacy and safety, an additional dosing cohort may be evaluated. The primary endpoint is complete response (CR) rate at three months. Secondary endpoints include time to recurrence, the median duration of response, recurrence free survival (RFS), progression free survival (PFS), safety and tolerability.
o
Cleared Phase 2 ACH IND with US FDA – BEACH301. The study is a Phase 2, multicenter, open-label, dose-escalation/dose-expansion study evaluating TYRA-300 in children ages 3 to 10 with achondroplasia with open growth plates. The study will enroll children who are treatment-naïve (Cohort 1) and those who have received prior growth-accelerating therapy (Cohort 2) at multiple sites across the globe. Each of these cohorts is expected to enroll up to 10 participants per dose level (0.125, 0.25, 0.375, 0.50 mg/kg) for up to 12 months. The study will initially enroll a safety sentinel cohort of up to 3 treatment-naïve participants per dose level in children ages 5 to 10.

o
Reported Interim Clinical Proof-of-Concept Results in mUC Patients – SURF301. TYRA-300 demonstrated encouraging preliminary anti-tumor activity in a heavily pre-treated population: at ≥ 90 mg QD, 6 out of 11 (54.5%) patients with FGFR3+ mUC achieved a confirmed partial response (PR), with 100% disease control rate and sustained duration of activity; positive safety results were reported across all QD doses, with infrequent FGFR2/FGFR1-associated toxicities (data cutoff of August 15, 2024). TYRA-300 is being evaluated in Part B of SURF301 (NCT05544552) at potentially therapeutic QD doses in preparation for potential future Phase 2 studies.

TYRA-200

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Advanced Phase 1 SURF201 Study. TYRA-200 is an FGFR1/2/3 inhibitor with potency against activating FGFR2 gene alterations and resistance mutations. SURF201 (Study in PrevioUsly treated and Resistant FGFR2+ Cholangiocarcinoma and Other Advanced Solid Tumors) (NCT06160752) is a multi-center, open label study designed to evaluate the safety, tolerability, and pharmacokinetics of TYRA-200 and determine the optimal and maximum tolerated dose and recommended Phase 2 dose, as well as evaluate the preliminary antitumor activity of TYRA-200. The SURF201 study is currently enrolling and dosing adults with unresectable locally advanced/metastatic intrahepatic cholangiocarcinoma and other advanced solid tumors with activating FGFR2 gene alterations.

TYRA-430

•
Cleared Phase 1 IND with US FDA – SURF431. TYRA-430 is an oral, investigational FGFR4/3-biased inhibitor for FGF19+/FGFR4-driven cancers. The Phase 1 study will be a multicenter, open-label, first-in-human study of TYRA-430 in advanced hepatocellular carcinoma (HCC) and other solid tumors with activating FGF/FGFR pathway aberrations (SURF431). We believe TYRA-430 has the potential to address a significant unmet need in HCC, where there are no approved biomarker-driven, targeted therapies.

Corporate

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Strengthened Leadership Team and Board of Directors. In 2024, TYRA appointed Doug Warner, MD, as Chief Medical Officer, and Erik Goluboff, MD, as SVP, Clinical Development to lead the Company’s oncology strategy and clinical development plans. In 2025, TYRA appointed accomplished drug developer Adele Gulfo to its Board of Directors, Sinette Heys as SVP, Clinical Operations to lead the Company’s clinical operations team, and Will Charlton, MD, as SVP, Clinical Development to lead the Company’s skeletal dysplasia clinical development group.

SNÅP Platform and Pipeline

•
TYRA continued to advance its in-house precision medicine discovery engine, SNÅP, to develop therapies in targeted oncology and genetically defined conditions.

Fourth Quarter and Full-Year 2024 Financial Results

•
Cash, Cash Equivalents and Short-Term Investments. As of December 31, 2024, TYRA had cash, cash equivalents, and marketable securities of $341.4 million, compared to $203.5 million at the end of 2023. The increase was primarily due to the completion of a private placement financing for net proceeds of $199.6 million in the first quarter of 2024. The Company’s current cash, cash equivalents and marketable securities are expected to allow TYRA to execute on its plans through at least 2027.
•
Research and Development (R&D) Expenses. Research and development expenses for the three months ended December 31, 2024 were $22.2 million compared to $20.7 million for the same period in 2023, and $80.1 million for the full year 2024 compared to $62.5 million for the same period in 2023. The increases were primarily driven by increased expenses incurred in connection with our ongoing and planned clinical trials and personnel-related costs, including stock-based compensation, partially offset by decreased drug manufacturing and preclinical costs.
•
General and Administrative (G&A) Expenses. General and administrative expenses for the three months ended December 31, 2024 were $7.6 million compared to $5.0 million for the same period in 2023, and $24.1 million

for the full year 2024 compared to $17.4 million for the same period in 2023. The increases were primarily driven by increased personnel-related costs, including stock-based compensation.
•
Net Loss. Fourth quarter 2024 net loss was $25.6 million compared to $22.8 million for the same period in 2023, and $86.5 million for the full year 2024 compared to $69.1 million for the same period in 2023.

Upcoming Anticipated Milestones and Events

•
BEACH301: dose first child with achondroplasia with TYRA-300 – Q2 2025
•
SURF302: dose first NMIBC patient with TYRA-300 – Q2 2025
•
SURF431: dose first HCC patient with TYRA-430 – Q2 2025

About TYRA-300

TYRA-300 is the Company’s lead precision medicine program stemming from its in-house SNÅP platform. TYRA-300 is an investigational, oral, FGFR3-selective inhibitor currently in development for the treatment of cancer and skeletal dysplasia, including achondroplasia and hypochondroplasia. In oncology, TYRA-300 is being evaluated in mUC and IR NMIBC. In mUC, TYRA-300 is being evaluated in a multi-center, open label Phase 1/2 clinical study, SURF301 (Study in Untreated and Resistant FGFR3+ Advanced Solid Tumors) (NCT05544552). The study is designed to determine the optimal and the recommended Phase 2 dose of TYRA-300, as well as to evaluate the preliminary antitumor activity of TYRA-300. In October 2024, TYRA reported interim clinical proof-of-concept data in mUC from SURF301. TYRA has received IND clearance from the US FDA to proceed with its SURF302 clinical trial in patients with IR NMIBC. In skeletal dysplasia, TYRA-300 has demonstrated positive preclinical results in achondroplasia and hypochondroplasia, and its BEACH301 clinical trial in children with achondroplasia is now recruiting.

About TYRA-200

TYRA-200 is an oral, investigational, FGFR1/2/3 inhibitor with potency against activating FGFR2 gene alterations and resistance mutations. The Phase 1 clinical study of TYRA-200, SURF201 (Study in PrevioUsly treated and Resistant FGFR2+ Cholangiocarcinoma and Other Advanced Solid Tumors) (NCT06160752), is a multi-center, open label study designed to evaluate the maximum tolerated dose (MTD) and the recommended Phase 2 dose of TYRA-200, as well as to evaluate the preliminary antitumor activity of TYRA-200. SURF201 is currently enrolling and dosing adults with advanced/metastatic intrahepatic cholangiocarcinoma and other advanced solid tumors with activating alterations in FGFR2.

About TYRA-430

TYRA-430 is an oral, investigational FGFR4/3-biased inhibitor for FGF19+/FGFR4-driven cancers. The US FDA has cleared Tyra’s IND to proceed with a Phase 1 clinical study of TYRA-430. The Phase 1 study will be a multicenter, open-label, first-in-human study of TYRA-430 in advanced HCC and other solid tumors with activating FGF/FGFR pathway aberrations (SURF431).

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]).

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"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]).

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"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]).

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"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.

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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."