8-K: Lisata Therapeutics Advances Certepetide to Global Phase 3

Lisata Therapeutics, Inc. announced its corporate presentation highlighting the advancement of its lead product candidate, certepetide, to a global Phase 3 clinical trial for metastatic pancreatic ductal adenocarcinoma, supported by positive Phase 2b data and a strong financial position.

Summary

• Lisata Therapeutics is a clinical-stage pharmaceutical company developing innovative therapies for cancer and other serious diseases, with a primary focus on solid tumors, particularly metastatic pancreatic ductal adenocarcinoma (mPDAC).
• The company's lead product candidate, certepetide (an iRGD cyclic peptide adjuvant), is designed to enhance the delivery of anti-cancer agents, modify the tumor microenvironment, and inhibit metastasis.
• Certepetide has demonstrated improved overall survival (OS) in two independent Phase 1b/2a trials (CEND1-201 in China with 13.2 months mOS and CEND1-001 in Australia with 11.1 months mOS) when combined with gemcitabine and nab-paclitaxel, compared to historical standard of care (8.5 months).
• The ASCEND Phase 2b study in mPDAC showed that Cohort B (two IV pushes of certepetide) achieved a median Progression-Free Survival (PFS) of 7.46 months versus 5.29 months for standard of care (HR 0.61, p=0.09), nearing statistical significance.
• In ASCEND Cohort B, the Objective Response Rate (ORR) was 45% for certepetide-treated patients versus 19% for placebo, with 1 complete response in the certepetide group compared to zero in the placebo group (statistically significant excluding unknown/early withdrawal/death).
• Median OS in ASCEND Cohort B was 10.32 months for certepetide versus 9.23 months for standard of care, while Cohort A (one IV push) showed 12.68 months versus 9.23 months, both numerically favoring certepetide.
• Certepetide has a strong intellectual property portfolio with global protection extending beyond 2040, including composition of matter patents.
• The company holds FDA Fast Track, Orphan Drug (for pancreatic cancer, malignant glioma, osteosarcoma, cholangiocarcinoma), and Rare Pediatric Disease (for osteosarcoma) designations, the latter making it eligible for a Priority Review Voucher.
• Lisata has secured strategic partnerships with Catalent, GATC Health Corp., Kuva Labs, and Qilu Pharmaceutical, generating upfront payments and potential milestones/royalties, including $15 million collected from Qilu to date.
• The company reported $22.0 million in cash and investments as of June 30, 2025, with no debt, providing a projected cash runway into the first quarter of 2027.
• An End-of-Phase 2 FDA meeting on May 21, 2025, resulted in agreement on the design for a global Phase 3 clinical trial for certepetide in 1L mPDAC, targeting 657 patients across approximately 183 sites in 15 countries, with Overall Survival as the primary endpoint.

Sentiment

Score: 8

Explanation: The company demonstrates strong clinical progress with its lead candidate, certepetide, showing positive Phase 2b data and a clear, agreed-upon path to a global Phase 3 trial for mPDAC. This is supported by a solid financial position with no debt and a cash runway into 1Q 2027, robust intellectual property, and strategic partnerships. While one cohort's primary endpoint was not statistically significant, the overall clinical picture, especially with the optimized dosing regimen, is highly encouraging and de-risks future development.

Positives

• Strong cash and investments of $22.0 million as of June 30, 2025, with no debt, providing a projected cash runway into 1Q 2027.
• Positive clinical data from ASCEND Phase 2b Cohort B, showing median PFS nearing statistical significance (7.46 months vs. 5.29 months, HR 0.61, p=0.09) and a statistically significant Objective Response Rate (45% vs. 19%) for certepetide.
• Overall Survival data from ASCEND Cohort A (12.68 months) and Cohort B (10.32 months) numerically favored certepetide over standard of care (9.23 months).
• Agreement with the FDA on the design of a global Phase 3 clinical trial for certepetide in 1L mPDAC, providing a clear regulatory pathway.
• Robust intellectual property portfolio with global protection extending beyond 2040, including composition of matter patents.
• Multiple strategic partnerships (Catalent, GATC Health, Kuva Labs, Qilu Pharmaceutical) validate the platform technology and provide non-dilutive funding and potential future revenue streams.
• Receipt of FDA Fast Track, Orphan Drug, and Rare Pediatric Disease designations, offering regulatory benefits and potential for a Priority Review Voucher.
• Certepetide demonstrated a benign safety profile, with adverse events reflecting the companion chemotherapy.
• Preliminary efficacy data from the iLSTA Phase 1b/2a trial in locally advanced PDAC showed a 69% Overall Response Rate and 100% Disease Control Rate in Cohort 3, indicating strong activity in combination with chemo and immunotherapy.
• A sustained complete response for over 37 months was observed in a metastatic gastroesophageal adenocarcinoma patient treated with certepetide in combination with standard therapy.

Negatives

• The ASCEND Phase 2b Cohort A, powered for 6-month PFS, did not show a statistically significant improvement with certepetide (5.55 months vs. 5.29 months for SoC).
• The median Overall Survival in ASCEND Cohort B (10.32 months) was numerically lower than Cohort A (12.68 months), despite Cohort B showing stronger PFS and ORR trends.
• The Priority Review Voucher program, which Lisata is eligible for, is set to expire in September 2026 and may not be renewed, potentially reducing a significant future asset value.

Risks

• The safety and efficacy of Lisata's product candidates are subject to ongoing clinical evaluation and regulatory approval.
• Decisions of regulatory authorities and the timing thereof, including potential regulatory delays in clinical programs, could impact development timelines.
• The company's ability to finance its operations and successfully initiate and complete clinical trials depends on adequate capital.
• The likelihood and timing of receiving future milestone and licensing fees from partnerships are uncertain.
• The future success of Lisata's scientific studies and its ability to successfully develop and commercialize drug candidates are not guaranteed.
• The time and cost of developing product candidates are difficult to predict and may exceed current estimates.
• Rapid technological change in Lisata's markets could impact the competitive landscape.
• The ability of Lisata to protect its intellectual property rights is crucial for its long-term success.
• Legislative, regulatory, political, and economic developments could adversely affect the company's operations and financial performance.
• The Priority Review Voucher program is scheduled to expire in September 2026 and may not be renewed, which could eliminate a potential source of significant value.

Future Outlook

Lisata Therapeutics is poised to initiate a global Phase 3 clinical trial for certepetide in first-line metastatic pancreatic ductal adenocarcinoma (mPDAC), following agreement with the FDA on the study design. The company anticipates multiple product and business milestones over the next 12 months, including final data from the ASCEND Phase 2b study in 4Q 2025, final 6-month PFS/OS data from the iLSTA trial in 1Q 2026, and 2L OS data from the BOLSTER trial by mid-2026. Lisata also plans to continue evaluating certepetide in various solid tumors and non-oncologic applications, leveraging existing and potential new partnerships.

Management Comments

• David J. Mazzo, PhD, President & CEO, was recently recognized as a 2024 PharmaVoice Top 100 Standout Leader, highlighting his strategic prowess and extensive experience in drug development and launches.

Industry Context

The global need for improved solid tumor treatments remains vital and growing, with cancer incidence projected to rise significantly by 2050. Pancreatic ductal adenocarcinoma (PDAC) is particularly challenging, predicted to be the second most common cause of cancer mortality by 2030, with immunotherapies generally proving ineffective. Certepetide's unique mechanism, which addresses the physical barrier of tumor stroma and the immunosuppressive tumor microenvironment, positions it as a potentially transformative therapy in areas where current treatments are suboptimal. Its broad applicability across various solid tumors and compatibility with multiple anti-cancer modalities (chemotherapy, immunotherapy) aligns with the industry's shift towards combination therapies and targeted drug delivery to overcome tumor resistance.

Comparison to Industry Standards

• Certepetide's median Overall Survival (OS) of 13.2 months in the CEND1-201 trial and 11.1 months in the CEND1-001 trial, when combined with gemcitabine and nab-paclitaxel, compares favorably to the 8.5 months OS established by the Von Hoff 2013 Phase 3 study for standard of care (gemcitabine + nab-paclitaxel).
• The observed OS separation at 7 months in ASCEND Cohort A and B is similar to the NALIRIFOX Phase 3 study data, a recently FDA-approved triplet therapy for mPDAC, suggesting a comparable clinical benefit profile.
• The statistically significant Objective Response Rate (ORR) of 45% in ASCEND Cohort B for certepetide plus standard of care, compared to 19% for placebo, indicates a strong clinical effect relative to typical response rates for mPDAC standard therapies.
• The case of complete response in metastatic gastroesophageal adenocarcinoma with certepetide added to FOLFIRINOX, radiotherapy, and pembrolizumab demonstrates potential beyond mPDAC, aligning with the industry's pursuit of multi-modal and combination therapies for difficult-to-treat cancers.

Stakeholder Impact

• **Shareholders:** Potential for significant value appreciation due to positive clinical trial results, advancement to Phase 3, strong IP, and strategic partnerships. The cash runway provides stability.
• **Patients:** Potential for improved treatment outcomes in difficult-to-treat cancers like mPDAC, cholangiocarcinoma, and GBM, offering new therapeutic options where current standards are suboptimal.
• **Employees:** Stable employment and potential for growth as the company advances its clinical programs and expands its pipeline.
• **Partners (Catalent, GATC, Kuva, Qilu):** Continued collaboration and potential for shared success as certepetide progresses through development and commercialization, validating their investments and strategic alliances.
• **Regulatory Authorities:** Continued engagement with FDA and other global health authorities for clinical trial oversight and eventual marketing approval.

Next Steps

• Initiate a global Phase 3 clinical trial for certepetide in first-line metastatic pancreatic ductal adenocarcinoma (mPDAC) with a design agreed upon with the FDA.
• Present final data from the ASCEND Phase 2b study in 4Q 2025.
• Obtain final 6-month PFS/OS data from the iLSTA Phase 1b/2a trial in locally advanced PDAC, expected in 1Q 2026.
• Receive 2L OS data from the BOLSTER Phase 2a trial in cholangiocarcinoma, targeted for mid-2026.
• Continue preclinical data generation for the Catalent ADC program.
• Advance ongoing Phase 2a trials for certepetide in cholangiocarcinoma (BOLSTER), pancreatic, colon, and appendiceal cancers (CENDIFOX), and Glioblastoma Multiforme (GBM).
• Continue development of certepetide in China through the Qilu Phase 2b trial in mPDAC.

Key Dates

Recommendation

The company has demonstrated compelling clinical efficacy for certepetide in mPDAC, particularly with the two-dose regimen in ASCEND Cohort B, showing improved OS and a statistically significant ORR. The clear agreement with the FDA on a global Phase 3 study design significantly de-risks the development pathway. Coupled with a strong cash position extending into Q1 2027, no debt, robust intellectual property, and multiple strategic partnerships, Lisata Therapeutics is well-positioned for substantial growth. The potential for a Priority Review Voucher from the Rare Pediatric Disease designation adds further upside, making it an attractive investment for seasoned investors.

Keywords

Lisata Therapeutics, LSTA, Certepetide, iRGD, Pancreatic Cancer, mPDAC, Cholangiocarcinoma, Glioblastoma, Oncology, Solid Tumors, Clinical Trials, Phase 3, Biopharmaceutical, Cancer Therapy, Drug Development, Tumor Microenvironment, Immunotherapy, FDA Fast Track, Orphan Drug