FDA Grants Orphan Drug Designation to LYT-200 for Pancreatic Cancer

The FDA has granted an orphan drug designation to LYT-200, a fully human IgG4 monoclonal antibody targeting galectin-9, for use as a potential therapeutic option for patients with pancreatic cancer.

The FDA has granted an orphan drug designation to LYT-200, a fully human IgG4 monoclonal antibody targeting galectin-9, for use as a potential therapeutic option for patients with pancreatic cancer.1

Recent research has indicated a mechanism by which PD-1 and galectin-9 interact to protect cancer from the immune system, underscoring that galectin-9 is a ligand for PD-1, which makes it an encouraging target for immunotherapeutics.2 PD-1 was found to interact with galectin-9 and TIM-3 to weaken T-cell apoptosis induced by those markers to keep effector T cells in the tumor microenvironment in an exhausted functional state. Moreover, interferons were found to upregulate galectin-9 expression and secretion substantially in immune and cancer cells. This information suggests that galectin-9 serves as a key regulator of immune response to cancer.

Preclinical data have shown that galectin-9 is highly expressed across breast and pancreatic cancers, as well as cholangiocarcinoma. The highest levels of this biomarker have been linked with shorter time to disease relapse and worse survival. The efficacy of LYT-200 has been demonstrated in preclinical and patient-derived organoid tumor models.

An open-label, uncontrolled, multicenter phase 1/2 study (NCT04666688) is evaluating the safety, pharmacokinetics, and antitumor activity of LYT-200 both as a single agent, and in combination with either chemotherapy or anti–PD-1 therapy in patients with metastatic solid tumors.

“The FDA’s decision to grant orphan drug designation for LYT-200 reflects its potential as a novel anticancer therapy designed to block multiple immunosuppressive pathways in the tumor microenvironment,” Julie Krop, MD, chief medical officer at PureTech Health plc, stated in a press release. “Too many [patients with] pancreatic cancer do not respond to existing immunotherapy agents and other standard-of-care regimens. We look forward to advancing LYT-200 through the clinic in hopes of meeting this substantial need.”

The ongoing phase 1/2 trial is slated to enroll approximately 250 participants. To be eligible for participation, patients need to be at least 18 years of age, have histologically confirmed unresectable metastatic cancer, a life expectancy of longer than 3 months, an ECOG performance status of 0 or 1, measurable disease per RECIST v1.1 criteria, and acceptable hematologic and end organ function.3

If patients were diagnosed with metastatic cancer of an unknown primary, had prior or current illicit drug addiction, are receiving any other investigational drugs, or are participating in any other clinical trials evaluating an investigative agent for solid tumor treatment, or they received radiation therapy within 4 weeks prior to the first dose of study treatment, they were excluded. Patients could not have clinically significant, active uncontrolled bleeding, nor could they have a bleeding diathesis.

The trial is comprised of 2 parts: a dose-escalation phase and a cohort expansion phase. The first phase of the trial will be conducted utilizing a continuous reassessment method to determine dose-limiting toxicities (DLTs) and identify the recommended phase 2 dose (RP2D). The second portion of the research will adopt a Simon’s 2-stage optimal design and will include expansion cohorts for specific solid tumors like pancreatic cancer and cholangiocarcinoma, among others.

The primary outcome measures for the first part of the research include incidence of treatment-emergent adverse effects and the incidence of DLTs. For part 2, the primary focus is looking at progression-free survival or objective response rate to gain insight into preliminary efficacy.

Secondary outcome measures for parts 1 and 2 include looking into the pharmacokinetic profile of LYT-200, specifically to characterize the maximum plasma concentration, time to maximum plasma concentration, and the area under the curve.

Investigators are also evaluating the pharmacodynamics of the agent, specifically immunophenotyping peripheral blood mononucleocyte samples and tumor tissue, performing cytokine profiling of serum samples, looking at galectin-9 expression levels, and evaluating antidrug antibodies.

Topline data from the phase 1 portion of the research is anticipated to be available in the first half of 2022 to permit continued dose escalation. The maximum tolerated dose for LYT-200 has not yet been reached.


  1. PureTech receives orphan drug designation for wholly owned candidate LYT-200 for the treatment of pancreatic cancer. News release. PureTech Health PLC. November 11, 2021. Accessed November 11, 2021. https://bit.ly/3D7vkEz
  2. Monoclonal antibody targeting galectin-9 in development for the potential treatment of solid tumors. PureTech Health PLC website. Accessed November 11, 2021. https://bit.ly/3He60yX
  3. LYT-200 alone and in combination with chemotherapy or anti-PD-1 in patients with metastatic solid tumors. ClinicalTrials.gov. Updated April 6, 2021. Accessed November 11, 2021. https://clinicaltrials.gov/ct2/show/NCT04666688