Lisata Therapeutics(LSTA) - 2025 Q1 - Quarterly Results

Company Overview This section provides an overview of Lisata Therapeutics, including its core focus, key strengths, and leadership team Lisata at a Glance Lisata Therapeutics (Nasdaq: LSTA) is a clinical-stage company developing certepetide, a novel technology designed to improve the treatment of solid tumors by enhancing the penetration and effectiveness of anti-cancer therapies - Lisata is a clinical-stage company focused on a novel solid tumor targeting and penetration technology that modifies the tumor microenvironment (TME)[8] - The company's mission is to improve the efficacy of existing and new solid tumor therapies without adding side effects, using a patient-friendly and cost-effective approach[10] - Key attributes include experienced management, proprietary technology with global IP protection beyond 2040, and multiple milestones expected in the next 12-18 months[12][13] - The company has a cash runway extending into Q3 2026 with no debt, sufficient to fund its current clinical programs[15] Leadership The company is led by a seasoned management team with a proven track record of successful drug approvals worldwide - President and CEO, David J. Mazzo, PhD, is a global pharmaceutical executive with over 40 years of experience in developing and launching new products[18] - EVP of R&D and Chief Medical Officer, Kristen K. Buck, MD, is a board-certified physician with over 20 years of experience in strategic global drug development, safety, and FDA interactions[18] Therapeutic Focus and Rationale This section details the significant unmet need in solid tumor treatment and introduces certepetide as a novel solution to overcome these challenges The Unmet Need in Solid Tumors There is a significant and growing global need for improved solid tumor treatments, as cancer incidence is projected to rise substantially by 2050 Projected Worldwide Cancer Incidence | Year | New Cases | Deaths | | :--- | :--- | :--- | | 2022 | 20 million | 10 million | | 2050 (Projected) | 35 million | 18.5 million | - Solid tumors account for more than 90% of all diagnosed cancers[23] - The tumor stroma acts as a physical barrier, and the immunosuppressive TME contributes to tumor resistance, hindering the efficacy of anti-cancer therapies[27] Certepetide as a Solution Certepetide is a proprietary iRGD cyclic peptide designed to overcome the challenges of solid tumor treatment - Certepetide is a proprietary internalizing RGD (iRGD) cyclic peptide with tumor-specific targeting and penetration activity[28] - It functions by converting tumor stroma into a conduit for drugs, reducing immunosuppressive T cells, recruiting cytotoxic T cells, and inhibiting the metastatic cascade[29] - The drug is approaching Phase 3 readiness in metastatic pancreatic ductal adenocarcinoma (mPDAC) and is compatible with any modality of anti-cancer therapeutic via co-administration[29] Partnerships Lisata has established several strategic partnerships that validate its technology and provide non-dilutive funding and resources Key Strategic Partnerships | Partner | Agreement Details | | :--- | :--- | | Qilu Pharmaceutical | Exclusive rights in Greater China. Lisata has received $15 million in milestones and is eligible for an additional $221 million plus royalties. Qilu covers all costs in its territories | | Kuva Labs | Exclusive worldwide rights for diagnostic tumor imaging. Lisata received a $1 million upfront fee and is eligible for ~$20 million in milestones plus royalties | | Catalent, Inc. | Preclinical evaluation of certepetide with Catalent's SMARTag® ADC platform. Catalent assumes R&D costs | | Valo Therapeutics | Preclinical investigation combining certepetide with Valo's oncolytic adenovirus platform for melanoma treatment | - The company has R&D alliances with clinical trialist consortiums like the Australasian Gastro-Intestinal Trials Group (AGITG) and the WARPNINE foundation[33] Certepetide Scientific Foundation This section elucidates the detailed mechanism of action of certepetide, supported by extensive preclinical evidence, and outlines the company's strategic development approach Mechanism of Action (MOA) Certepetide utilizes a unique, multi-step mechanism to enhance drug delivery to tumors - Step 1: Integrin Binding: Certepetide, a 9-amino acid cyclic peptide, binds with high specificity to ανβ3 and/or ανβ5 integrins upregulated on tumor cells[37] - Step 2 & 3: Cleavage and NRP-1 Binding: The bound peptide is cleaved in the TME, creating a CendR fragment that binds to the adjacent Neuropilin-1 (NRP-1) receptor[37][38] - Step 4: Tumor Penetration: This binding activates the CendR active transport pathway, which encapsulates and ferries circulating anti-cancer drugs into the tumor[38][40] Preclinical Evidence Extensive preclinical data from over 370 scientific publications consistently demonstrate certepetide's ability to enhance the efficacy of various anti-cancer treatments - Whole-body imaging in mouse models demonstrates that certepetide selectively promotes the accumulation of co-administered agents within tumor tissue[43][45] - Numerous preclinical studies have shown improved survival when certepetide is combined with various therapies, including gemcitabine in lung cancer, nab-paclitaxel in breast cancer, and irinotecan nanoparticles in pancreatic cancer[49][51][57][58] - In a cholangiocarcinoma mouse model, certepetide combined with standard-of-care chemo- and immunotherapy improved survival, reduced morbidity, and inhibited metastasis[67] - Certepetide enhances the selective tumor penetration of monoclonal antibodies, as demonstrated with trastuzumab in a human breast tumor mouse model, leading to greater tumor shrinkage[69][70] Development Strategy Lisata employs a two-pillar development strategy for certepetide - Pillar 1: Pursue rapid global registration in mPDAC, initially combined with the gemcitabine/nab-paclitaxel standard-of-care, with Phase 3 preparation underway[72][73] - Pillar 2: Demonstrate certepetide's effectiveness across a variety of solid tumors and treatment regimens (chemotherapy, immunotherapy, etc.) through multiple ongoing Phase 2a studies[72] Certepetide Clinical Development This section presents the clinical data for certepetide in metastatic pancreatic ductal adenocarcinoma and other solid tumors, outlining the path forward and regulatory designations Clinical Data in mPDAC Clinical data for certepetide in metastatic pancreatic ductal adenocarcinoma (mPDAC) is promising Phase 1 Median Overall Survival (mOS) in mPDAC | Trial | Treatment | mOS (Months) | Improvement vs. SoC | | :--- | :--- | :--- | :--- | | Von Hoff 2013 (SoC) | Gemcitabine + Nab-paclitaxel | 8.5 | - | | CEND1-001 (Australia) | SoC + Certepetide | 13.2 | 55% | | CEND1-201 (China) | SoC + Certepetide | 11.1 | 31% | ASCEND Phase 2b (Cohort A) Preliminary Overall Survival | Treatment Arm | N | Median OS (Months) | | :--- | :--- | :--- | | Certepetide | 66 | 12.68 | | Placebo | 29 | 9.72 | - In the ASCEND trial's Cohort A, the primary endpoint of Progression-Free Survival (PFS) was not met (HR: 0.94, p=0.79)[83][84] - A key finding from ASCEND Cohort A was the observation of 4 complete responses in the certepetide arm, compared to 0 complete responses in the placebo arm[90] Clinical Data in Other Solid Tumors Certepetide has shown remarkable activity in other solid tumors beyond pancreatic cancer - A patient with metastatic gastroesophageal adenocarcinoma (mGEAC) achieved a sustained complete response for over 31 months after certepetide was added to his treatment regimen, following a partial response to standard of care[80] Clinical Data Summary & Path Forward To date, certepetide has demonstrated a favorable safety profile with no dose-limiting toxicities and has shown improved overall survival in mPDAC across multiple trials - Certepetide has been well tolerated in clinical trials, with no dose-limiting toxicity observed[92] - Final, definitive data from the ASCEND Phase 2 trial's Cohort B are expected by mid-2025[92] - Preparations for a Phase 3 trial are currently underway[92] Regulatory Designations & Development Portfolio Certepetide has secured several valuable regulatory designations from the FDA and EMA, including Fast Track for pancreatic cancer and multiple Orphan Drug Designations - Certepetide has received FDA Fast Track Designation for pancreatic cancer, enabling more frequent communication with the FDA and eligibility for accelerated approval[94][95] - The drug has been granted Orphan Drug Designations for pancreatic cancer (FDA & EMA), malignant glioma (FDA), osteosarcoma (FDA), and cholangiocarcinoma (FDA), providing tax credits, fee waivers, and marketing exclusivity[94][95] Certepetide Clinical Development Pipeline Overview | Trial Name | Indication | Phase | Status | | :--- | :--- | :--- | :--- | | ASCEND | First-line mPDAC | 2b | Enrollment complete | | BOLSTER | Cholangiocarcinoma | 2a | Enrollment complete | | CENDIFOX | Pancreatic, Colon, Appendiceal | 1b/2a | Enrollment complete | | Qilu Trial | First-line mPDAC (China) | 1b/2a | Enrollment complete | | iLSTA | Locally advanced PDAC | 1b/2a | Enrolling | | Tartu Univ. Trial | Glioblastoma (GBM) | 2a | Enrolling | | Qilu Trial | First-line mPDAC (China) | 2 | Enrollment complete | | FORTIFIDE | First-line mPDAC | 1b/2a | Enrollment pending | Clinical Development Milestones Lisata has a rich pipeline of anticipated clinical milestones over the next 18 months - ASCEND (mPDAC): Final Progression-Free Survival (PFS) and Overall Survival (OS) data for both Cohort A and B are anticipated in Q2 2025[101] - BOLSTER (Cholangiocarcinoma): Second-line OS data is expected in Q2 2025, with first-line OS data targeted for mid-2026[101] - Qilu Phase 1b/2a (mPDAC in China): Final data from this trial is expected in Q2 2025[101] - iLSTA (Locally Advanced PDAC): Last patient in (LPI) is targeted for Q2 2025, with final 6-month PFS/OS data expected in Q4 2025[101] Financial Highlights As of March 31, 2025, Lisata Therapeutics is in a strong financial position with $25.8 million in cash and investments and no debt Financial Snapshot (as of 3/31/2025) | Metric | Value | | :--- | :--- | | Cash & Investments | $25.8 million | | Debt | $0 | | Projected Cash Runway | Into 3Q 2026 | | Common Shares Outstanding | 8.6 million | | Options Outstanding | 1.5 million | | Warrants Outstanding | 1.5 million | Investment Summary The investment thesis for Lisata Therapeutics is built on several key pillars: a seasoned management team, a validated platform technology, robust global intellectual property, significant clinical milestones, and a strong capital position - People: Led by a seasoned management team with extensive international drug development and approval experience[106] - Partnering: The platform technology is validated by existing partnerships, with potential for many more[106] - Intellectual Property: Possesses proprietary, field-leading technology with global IP protection extending beyond 2040[106] - Milestones: Multiple product and business milestones are projected over the next 12-18 months[106] - Capital: Strong financial position with $25.8 million in cash, no debt, and funding to support the advancement of current clinical programs[106] Appendix: Clinical Trial Details This appendix provides detailed information on key clinical trials for certepetide, including their design, patient populations, and objectives ASCEND Trial (mPDAC) The ASCEND trial is a Phase 2b, randomized, double-blind study evaluating certepetide with standard-of-care (gemcitabine + nab-paclitaxel) in 158 patients with first-line mPDAC across Australia and New Zealand - Design: Phase 2b, randomized, double-blind, placebo-controlled trial[114] - Population: N=158 patients with first-line mPDAC[114] - Endpoints: Primary endpoint is Progression-Free Survival (PFS); secondary endpoints include Overall Survival (OS) and Objective Tumor Response Rate[114] CEND1-201 Trial (mPDAC in China) This Phase 1b/2a open-label trial, sponsored and funded by Qilu Pharmaceutical, evaluated the safety, pharmacokinetics, and preliminary efficacy of certepetide added to standard-of-care chemotherapy in 55 Chinese patients with advanced mPDAC - Sponsor: Qilu Pharmaceutical (funds all development in China)[118] - Design: Phase 1b/2a open-label study in Chinese patients with mPDAC[118] - Size: N=55 patients across ~15 sites[118] CENDIFOX Trial (Pancreatic, Colon, Appendiceal) CENDIFOX is an investigator-initiated Phase 1b/2a open-label trial conducted at the University of Kansas Medical Center - Sponsor: University of Kansas Medical Center (Investigator-initiated trial)[122] - Indications: Pancreatic (N=24), colon (N=15), and appendiceal (N=11) cancers[122] - Objective: Evaluate safety and therapeutic effect of certepetide with FOLFIRINOX-based therapies[122] BOLSTER Trial (Cholangiocarcinoma) BOLSTER is a Lisata-sponsored Phase 2 randomized, double-blind, placebo-controlled trial in the U.S - Sponsor: Lisata (U.S.)[126] - Population: N=69 patients with first-line (N=47) and second-line (N=22) cholangiocarcinoma[126] - Primary Endpoint: Overall Survival (OS)[126] Qilu Phase 2 Trial (mPDAC in China) This is a Phase 2b, double-blind, placebo-controlled, randomized study sponsored by Qilu Pharmaceutical in China - Sponsor: Qilu Pharmaceutical (funds all development in China)[131] - Design: Phase 2b, double-blind, placebo-controlled, randomized study[131] - Size: N=96 patients[131] iLSTA Trial (Locally Advanced PDAC) The iLSTA trial is a Phase 1b/2a study in Australia, funded by the WARPNINE charity, with Lisata providing the study drug - Sponsor: WARPNINE, Inc. (Australian charity)[135] - Population: N=30 patients with locally advanced non-resectable PDAC[135] - Objective: Determine if the treatment combination can make inoperable tumors operable[135] GBM Phase 2a Trial (Glioblastoma) This is an investigator-initiated Phase 2a, double-blind, placebo-controlled trial at Tartu University Hospital in Estonia and Latvia - Sponsor: Tartu University Hospital (Investigator-initiated)[142] - Indication: Newly diagnosed Glioblastoma Multiforme (GBM)[142] - Size: N=30 patients[142] FORTIFIDE Trial (mPDAC Continuous Infusion) FORTIFIDE is a planned Phase 1b/2a, double-blind, placebo-controlled study sponsored by Lisata in the U.S - Design: Phase 1b/2a study evaluating a 4-hour continuous infusion of certepetide[147] - Population: First-line mPDAC patients who have progressed on FOLFIRINOX[147] - Status: Enrollment is pending[147]