Certepetide

What is Certepetide?

Certepetide (development codes CEND-1 and LSTA1) is a 9-amino-acid cyclic tumor-homing peptide developed by Lisata Therapeutics (formerly Caladrium Biosciences) and licensed from Erkki Ruoslahti's group at the Sanford Burnham Prebys Medical Discovery Institute. The peptide is a chemically optimized member of the iRGD (internalizing RGD) family — synthetic peptides Ruoslahti's group developed to exploit a tumor-penetration pathway distinct from classical receptor-mediated drug delivery. Certepetide's mechanism involves a two-step receptor engagement: it first binds αv-integrins (specifically αvβ3 and αvβ5) on tumor vasculature, where proteolytic cleavage by tumor-associated proteases releases a fragment with an exposed C-terminal RXXR/K motif that engages neuropilin-1 (NRP-1) on the same vascular endothelium and adjacent tumor stroma. The NRP-1 engagement activates the CendR (C-end Rule) tissue-penetration pathway — a transient and tumor-selective increase in vascular and stromal permeability that enables enhanced delivery of co-administered chemotherapy, antibodies, nanoparticles, or other therapeutics into tumor tissue that would otherwise be poorly accessible. The mechanism distinguishes certepetide from antibody-drug conjugates and other receptor-targeted delivery approaches because the tumor-penetration effect operates on bystander co-administered drugs without requiring direct conjugation. The foundational work establishing the iRGD/CendR mechanism includes Sugahara's 2009 Cancer Cell paper on tissue-penetrating delivery (PMID 19962669) and the 2010 Science paper showing that co-administration of iRGD enhances cancer drug efficacy in animal models (PMID 20378772). Lisata Therapeutics has advanced certepetide through clinical development since the late 2010s, with the first-in-human Phase 1b trial in metastatic pancreatic ductal adenocarcinoma (PDAC) reported by Dean and colleagues in Lancet Gastroenterology and Hepatology 2022 (PMID 35803294) — the trial combined certepetide with the standard PDAC chemotherapy backbone of gemcitabine + nab-paclitaxel and reported acceptable safety with encouraging efficacy signals in a difficult-to-treat malignancy. Subsequent population pharmacokinetic work (Winning 2025 Clinical Pharmacology in Drug Development, PMID 39789733) and pharmacokinetic characterization (Järveläinen 2023 International Journal of Molecular Sciences, PMID 36982773) have refined the dosing and exposure framework. The development pipeline is widely misdescribed. BOLSTER, often cited as a planned Phase 3 pancreatic programme, is nothing of the kind: NCT05712356 is a completed Phase 2a double-blind, placebo-controlled randomised study of LSTA1 added to standard of care in advanced biliary tract cancers — cholangiocarcinoma and gallbladder cancer — which enrolled 66 patients, ran from May 2023 to April 2026, and has results posted. The pipeline comprises that completed biliary trial, the completed Phase 1b, the randomised Phase 2 ASCEND in pancreatic cancer, and the LSTA1-GBM-2A glioblastoma trial (combination with temozolomide; protocol published by Truusalu 2025 in BMJ Open, PMID 41248393). That glioblastoma trial does not appear on ClinicalTrials.gov at all — it is registered in the EU clinical trials system as 2023-506813-23-00, sponsored by Tartu University Hospital with Lisata funding, randomising 30 patients 2:1 across sites in Estonia and Latvia with overall survival as the primary endpoint, and recruiting since January 2024. Certepetide is investigational and not FDA-approved. The peptide represents a distinctive approach within oncology drug development — a non-cytotoxic delivery enhancer rather than a tumor-killing agent itself — and the clinical hypothesis is that it makes existing chemotherapy more effective in tumors that have been historically resistant to drug penetration — pancreatic cancer, glioblastoma and biliary tract cancer. Whether the encouraging Phase 1b and Phase 2 signals ever get tested at Phase 3 is the principal open question, and as of late 2026 it is a question about funding and sponsorship rather than about biology.

What Certepetide Is Investigated For

Certepetide is a clinical-trial-stage oncology investigational drug, not a consumer-research-channel peptide. The molecule is being developed for combination with standard-of-care chemotherapy in pancreatic ductal adenocarcinoma (the AGITG-led ASCEND randomized Phase 2 trial in metastatic first-line PDAC, NCT05042128, combined with gemcitabine + nab-paclitaxel; first-line CENDIFOX Phase 1b/2a with neoadjuvant FOLFIRINOX) and in glioblastoma multiforme (the LSTA1-GBM-2A Phase 2a trial, combined with temozolomide). The clinical hypothesis is that certepetide's tumor-penetrating mechanism — αv-integrin binding plus neuropilin-1-mediated CendR pathway activation — enables enhanced chemotherapy delivery into tumor tissue that has been historically poorly accessible to systemic drug therapy. The foundational work from Erkki Ruoslahti's group at Sanford Burnham (Sugahara 2009 Cancer Cell, 2010 Science) established the iRGD/CendR mechanism in animal models, and the first-in-human Phase 1b PDAC trial (Dean 2022 Lancet Gastroenterol Hepatol) demonstrated translation feasibility in patients. ASCEND Cohort A (ASCO GI 2025) and Cohort B (ESMO GI 2025) reported the first randomized Phase 2 efficacy signals — improved median OS and PFS versus placebo on the chemotherapy backbone. The developer's situation is the principal uncertainty and it deteriorated sharply in 2026. The Kuva Labs acquisition announced on March 6, 2026 was amended down from $5.00 to $4.00 per share, then failed: the tender offer expired on July 20, 2026 without Kuva accepting any shares because, in Lisata's words, Kuva 'has been unable to obtain sufficient financing for purposes of funding the Offer'. Lisata terminated the merger agreement on July 24, 2026, is owed a $2,000,000 termination fee, sued Kuva in the Delaware Court of Chancery on July 31, and cut its workforce by approximately 72% on August 3. It has since agreed a reverse merger with Marea Therapeutics. Lisata still lists certepetide as its candidate and was granted a new US method-of-use patent for it in October 2026, but it has delayed the readiness work for the planned Phase 3 to manage capital. A September 2026 tumor-homing-peptide field review in J Control Release (Ma et al., PMID 42749136) explicitly names certepetide as the leading clinical translational asset in the tumor-homing-peptide class — a useful external framing of where the program sits circa mid-to-late 2026. This is investigational oncology, not a peptide consumers self-administer. There is no clinical use outside Lisata-sponsored trials, no FDA approval, no validated dosing protocol for off-label use, and no consumer-research-channel positioning that makes practical sense. Patients with metastatic pancreatic cancer or glioblastoma should consult their oncology team about clinical-trial enrollment. The peptide is included in this directory because it represents a substantive advanced-stage oncology peptide drug development program with peer-reviewed translational data — distinct from research-channel peptide marketing and worth tracking as the Phase 3 readout approaches.

History & Discovery

The certepetide story begins with Erkki Ruoslahti's group at the Sanford Burnham Prebys Medical Discovery Institute (formerly the Burnham Institute) in La Jolla, California. Ruoslahti is a foundational figure in integrin biology — his 1980s work characterizing the RGD motif as the cell-attachment recognition sequence in fibronectin established a substantial portion of modern integrin pharmacology. In the late 2000s, Ruoslahti's lab applied phage-display screening of tumor-vasculature binding peptides to identify iRGD (internalizing RGD), a cyclic peptide that not only bound αv-integrins on tumor vasculature but also engaged neuropilin-1 after proteolytic cleavage — activating a tissue-penetration pathway that the group named the C-end Rule (CendR). The foundational publications came in rapid succession. The Sugahara 2009 Cancer Cell paper (PMID 19962669) introduced the iRGD/CendR mechanism with proof-of-concept tissue-penetration data. The Sugahara 2010 Science paper (PMID 20378772) extended the work to demonstrate that simple co-administration of iRGD with cancer drugs (without direct conjugation) enhances drug efficacy in animal tumor models — the translational concept that would eventually drive certepetide's clinical positioning as a delivery enhancer rather than a conjugated drug-targeting agent. The Alberici 2013 Cancer Research paper (PMID 23151901) on de novo design of tumor-penetrating peptides extended the mechanistic understanding. Lisata Therapeutics (formerly Caladrium Biosciences) licensed the certepetide development rights from Sanford Burnham and advanced the molecule through clinical development. The first-in-human Phase 1b trial in metastatic pancreatic ductal adenocarcinoma was reported by Dean and colleagues in Lancet Gastroenterology and Hepatology 2022 (PMID 35803294), combining certepetide (then called CEND-1) with the standard PDAC chemotherapy backbone of gemcitabine + nab-paclitaxel. The trial demonstrated translation feasibility with acceptable safety and encouraging efficacy signals, supporting advancement to the AGITG-led ASCEND randomized Phase 2 trial in metastatic first-line PDAC. The 2021 Hurtado de Mendoza Nature Communications paper (PMID 33750829) established β5 integrin upregulation in PDAC vasculature as a mechanistic rationale for PDAC as a particularly suitable indication. The 2023 Järveläinen IJMS paper (PMID 36982773) characterized the pharmacokinetics, disposition, and duration of CendR pathway activation. The 2025 Winning Clin Pharmacol Drug Dev paper (PMID 39789733) refined population pharmacokinetic modeling in metastatic PDAC patients. The LSTA1-GBM-2A Phase 2a glioblastoma protocol (Truusalu 2025 BMJ Open, PMID 41248393) extended the development program to a second high-unmet-need indication. The peptide received the International Nonproprietary Name 'certepetide' as part of the regulatory development process, alongside the development codes CEND-1, LSTA1, and the original research-name iRGD. The INN assignment reflects the advanced regulatory and clinical-trial infrastructure of the program. The randomized Phase 2 ASCEND trial (NCT05042128, AGITG-led, n=158 in mPDAC) reported its first cohort topline at ASCO GI 2025 — median OS 12.42–12.68 months on certepetide versus 9.72 months on placebo, with 4 complete responses on certepetide and 0 on placebo. Cohort B topline at ESMO GI 2025 reported median PFS 7.5 months versus 4.7 months and 6-month PFS 60.8% versus 25%. The CENDIFOX neoadjuvant Phase 1b/2a (KU Cancer Center) reported preliminary PDAC cohort data in September 2025 with 50% R0 resection and 70% pathologic partial response in resected patients. These randomized and neoadjuvant Phase 2 readouts are the strongest current evidence for certepetide. The corporate landscape shifted substantially in early 2026. On January 27, 2026, Lisata and Qilu Pharmaceutical mutually terminated their certepetide China license. On March 6, 2026, Kuva Labs announced an acquisition of Lisata at $5.00 per share in cash plus a contingent value right worth up to $1.00 per share if certepetide were filed with and accepted by the FDA, with closing expected in Q2 2026 and Lisata delisting from Nasdaq. It did not happen. The price was amended down to $4.00 per share, the tender offer expired one minute after 11:59 p.m. on July 20, 2026 without Kuva accepting any shares because, as Lisata's quarterly filing puts it, Kuva had been unable to obtain sufficient financing to fund the offer. Lisata terminated the merger agreement on July 24, 2026, is owed a $2,000,000 termination fee, and on July 31 commenced an action in the Delaware Court of Chancery against Kuva for breach. On August 3, 2026 its board approved a reduction in workforce of approximately 72%, effective immediately. What followed was a rescue rather than a recovery. In September 2026 Lisata agreed a reverse merger with Marea Therapeutics alongside a large private placement, a transaction that leaves legacy Lisata holders with a small minority of a combined company whose focus is Marea's cardiometabolic and endocrine pipeline. Certepetide itself has not been divested and the asset is still described as Lisata's, and in October 2026 a new US method-of-use patent covering certepetide in pancreatic and other solid tumors was granted, running to 2041. But the company told investors it had delayed the readiness activities for its planned Phase 3, particularly manufacturing work, to manage capital for short-term operating needs. No Phase 3 trial has ever been registered under certepetide, CEND-1, LSTA1 or iRGD. Whether the drug reaches a pivotal trial now depends on whoever ultimately champions it, and for the first time in the programme's history there is no obvious candidate.

How It Works

Certepetide is a tiny 9-amino-acid peptide developed by Lisata Therapeutics that acts like a key for tumors. When you give it alongside chemotherapy, it binds to the blood vessels feeding tumors, gets cut by tumor-associated enzymes, and then briefly opens up the tumor's normally-tight defenses so the chemotherapy drugs can actually reach the cancer cells. It doesn't kill cancer itself — it just makes the chemo drugs you're already getting much more effective. The lead use is for pancreatic cancer, which is famously hard to treat partly because chemo can't reach the tumor; a randomised Phase 2 there has finished and reported encouraging results. There's also a Phase 2 trial in glioblastoma. It is not FDA-approved, and despite years of statements about one, no Phase 3 trial has ever been registered — the developer said in mid-2026 that it had delayed the preparatory work for a Phase 3 to conserve cash.

Certepetide is a 9-amino-acid cyclic peptide (sequence cyclic-CRGDKGPDC, derived from the original iRGD scaffold) developed through chemical optimization of Erkki Ruoslahti's iRGD (internalizing RGD) platform at the Sanford Burnham Prebys Medical Discovery Institute. The mechanism involves a two-step receptor engagement that activates the C-end Rule (CendR) tissue-penetration pathway — a tumor-selective transient permeability increase that enables enhanced co-administered drug delivery. Step 1 — αv-integrin binding: Certepetide's RGD motif binds αv-integrins (specifically αvβ3 and αvβ5) on tumor vasculature endothelium. αv-integrins are upregulated on tumor blood vessels relative to normal vasculature, providing initial tumor-selective targeting. The integrin binding alone does not produce the tumor-penetration effect — it positions the peptide for the second step. Step 2 — Proteolytic cleavage and neuropilin-1 engagement: Tumor-associated proteases (predominantly furin-family proteases at the tumor vasculature) cleave certepetide between specific residues to expose a C-terminal RXXR/K motif. This exposed C-terminal motif then engages neuropilin-1 (NRP-1) on the same tumor vascular endothelium and adjacent tumor stroma. The NRP-1 engagement activates the CendR pathway — a vesicular transcytosis mechanism that produces transient and tumor-selective increases in vascular and stromal permeability. The CendR effect is paracrine in nature: once activated, it enhances penetration of bystander molecules (small-molecule chemotherapy drugs, antibodies, nanoparticles, oligonucleotides) into the tumor tissue without requiring direct conjugation. The Sugahara 2009 Cancer Cell paper (PMID 19962669) demonstrated the principle of tissue-penetrating delivery via iRGD-class peptides, and the 2010 Science paper (PMID 20378772) extended the work to show that simple co-administration of iRGD with cancer drugs (without conjugation) enhances drug efficacy in animal tumor models. The mechanism distinguishes certepetide from antibody-drug conjugates (which deliver payloads via direct conjugation to tumor-cell-targeting antibodies) and from receptor-targeted delivery approaches (which require conjugation of the targeting moiety to the therapeutic). Clinical pharmacokinetic characterization includes the Järveläinen 2023 IJMS paper (PMID 36982773) on PK, disposition, and duration of action, and the Winning 2025 Clinical Pharmacology in Drug Development paper (PMID 39789733) on population PK in metastatic PDAC patients. The duration of the effect is longer than the drug's own residence time, and this dissociation is one of the more interesting features of the molecule. Järveläinen and colleagues reported a plasma half-life of approximately 25 minutes in mice and 2 hours in patients; radiolabelled CEND-1 localised to tumour and several healthy tissues shortly after administration but was cleared from most healthy tissues by 3 hours, while tumours retained significant drug for several hours. In mice with hepatocellular carcinoma the tumour-penetration activity remained elevated for at least 24 hours after a single dose, leading the authors to conclude that even single injections may elicit long-lasting tumour pharmacokinetic improvements for co-administered agents. The permeability window is therefore not brief in the way earlier descriptions of the mechanism implied — the peptide is gone long before its effect is. The Hurtado de Mendoza 2021 Nature Communications paper (PMID 33750829) extended the mechanism to β5-integrin-rich pancreas cancer and established the mechanistic case for PDAC as a particularly suitable indication. The β5 integrin upregulation in PDAC vasculature, combined with the dense desmoplastic stroma that has historically limited PDAC chemotherapy efficacy, makes the tumor-penetration mechanism a well-matched therapeutic strategy. Suzuki, Ruoslahti, Sugahara and colleagues extended the mechanism further in Cancer Research August 2026 (PMID 42133398), reporting that αvβ5-integrin targeting via iRGD-family peptides depletes αvβ5-positive regulatory T cells and inhibits TGFβ activation in the PDAC tumor microenvironment — a new immunomodulatory pathway beyond the drug-delivery framing that opens combination logic with checkpoint inhibitors and TGFβ-axis modulators. Fukugaki et al. (Cancer Research Communications June 2026, PMID 42166776) followed with syngeneic mouse colorectal cancer data showing that iRGD combined with anti-PD-1 improves immunotherapeutic response — an early demonstration that the CendR mechanism can amplify checkpoint-inhibitor efficacy in tumor types beyond PDAC and glioblastoma. The same paper reports that stromal neuropilin-1 expression is prognostic for worse survival across 110 stage III colorectal cancer patients, which establishes that the target is present in human disease but does not test the drug in it.

Evidence Snapshot

Research Gaps & Open Questions

What the current literature has not yet settled about Certepetide:

• 01Whether a Phase 3 trial happens at all. None has ever been registered, and the developer stated in its June 2026 quarterly filing that it had delayed Phase 3 readiness activities — particularly manufacturing — to conserve capital, before cutting 72% of its staff and agreeing a reverse merger. This is now a sponsorship and financing question rather than a scientific one, and it sits upstream of every efficacy question below.
• 02Whether ASCEND's full results are ever published. The trial enrolled its full 158 patients and its registry record has not been updated since October 2024; overall status is listed as UNKNOWN, no results are posted, and the headline survival figures circulating for Cohorts A and B exist only in conference abstracts. For a randomised placebo-controlled Phase 2 in a disease with this much unmet need, that is a conspicuous gap.
• 03Whether the tumor-penetration mechanism translates from PDAC to glioblastoma (LSTA1-GBM-2A) and to other solid tumors with similar drug-penetration barriers.
• 04Whether certepetide can be combined with ADCs, immune-checkpoint inhibitors, or other novel oncology drug classes to produce additive tumor-penetration benefit. Fukugaki et al. (Cancer Res Commun 2026, PMID 42166776) provided the first NRP1-targeting-peptide-plus-anti-PD-1 preclinical support in colorectal cancer; whether this translates to human clinical benefit is untested.
• 05The optimal dosing schedule relative to chemotherapy administration — whether the brief CendR activation window can be optimized for different chemotherapy backbone pharmacokinetics.
• 06The mechanism's tumor-selectivity in advanced metastatic disease — whether the αv-integrin and neuropilin-1 expression profiles that drive PDAC tumor selectivity hold up across different tumor histologies.
• 07Long-term safety of repeated certepetide administration over multiple chemotherapy cycles, beyond the durations characterized in the Phase 1b and Phase 2 trials.

Forms & Administration

Certepetide is given intravenously as a bolus or slow IV push over roughly one minute — not as a prolonged infusion. The BOLSTER protocol specifies 3.2 mg/kg 'given as a slow IV push over 1 minute' when the standard treatments are given. In the ASCEND Phase 2 PDAC trial it is dosed at 3.2 mg/kg between the two chemotherapy agents, not before them: nab-paclitaxel 125 mg/m², then certepetide, then gemcitabine 1000 mg/m², on days 1, 8 and 15 of each 28-day cycle. ASCEND's Cohort B added a second 3.2 mg/kg dose approximately four hours later. In the LSTA1-GBM-2A Phase 2a glioblastoma trial, certepetide is combined with temozolomide. The peptide is supplied for trial use only. There is no FDA-approved formulation, no compounding-pharmacy or telehealth availability, and no validated off-trial dosing.

Dosing & Protocols

The ranges below reflect protocols commonly discussed in the literature and by clinicians — not a prescription. Actual dosing for any individual should be determined by a qualified healthcare provider who knows the patient.

Certepetide is investigational and not approved by any regulator. It is given only within clinical trials, alongside cytotoxic chemotherapy, under oncology supervision.

Timeline of Effects

Common Questions

Who Certepetide Is NOT For

Drug & Supplement Interactions

Documented drug-interaction data for certepetide come from the trial-stage development context. The intended interaction is with co-administered chemotherapy — certepetide is designed to enhance the tumor delivery of gemcitabine, nab-paclitaxel, temozolomide, and other chemotherapy backbone agents. The combination toxicity profile reflects the underlying chemotherapy plus minor additive contributions from the peptide, with the dominant adverse events attributable to the chemotherapy rather than the peptide. Interaction with concurrent supportive-care medications (anti-emetics, growth-factor support, transfusion support, etc.) follows the standard chemotherapy combination management. Patients enrolling in certepetide trials should disclose all concurrent medications to the trial team.

Safety Profile

Legal Status

Regulatory status changes over time. Verify current local rules with a qualified professional.

Myths & Misconceptions