LYT-100

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Discovery
Preclinical
Phase 1
Phase 2
Phase 3
LYT-100
Deupirfenidone
IPF & other progressive fibrosing ILDs

2

IPF & other progressive fibrosing ILDs

140–250K U.S. (PF-ILD including IPF) 


Product candidate being advanced for the potential treatment of conditions involving inflammation and fibrosis and disorders of lymphatic flow, including lung dysfunction conditions (e.g., idiopathic pulmonary fibrosis (IPF), unclassifiable interstitial lung diseases (uILDs), Long COVID respiratory complications and related sequelae) and lymphedema.

LYT-100
Deupirfenidone
Long COVID1 respiratory complications & related sequelae

2

Long COVID respiratory complications & related sequelae


Product candidate being advanced for the potential treatment of conditions involving inflammation and fibrosis and disorders of lymphatic flow, including lung dysfunction conditions (e.g., idiopathic pulmonary fibrosis (IPF), unclassifiable interstitial lung diseases (uILDs), Long COVID respiratory complications and related sequelae) and lymphedema.
LYT-100
Deupirfenidone
Lymphatic flow disorders, including lymphedema

2

Lymphatic flow disorders, incl. lymphedema

~1M U.S.

Product candidate being advanced for the potential treatment of conditions involving inflammation and fibrosis and disorders of lymphatic flow, including lung dysfunction conditions (e.g., idiopathic pulmonary fibrosis (IPF), unclassifiable interstitial lung diseases (uILDs), Long COVID respiratory complications and related sequelae) and lymphedema.
Phase completedPhase in progressRegistration-enabling studies planned

1. Long COVID is a term being used to describe the emerging and persistent complications following the resolution of COVID-19 infection.

An anti-inflammatory and anti-fibrotic small molecule 

PureTech's lead wholly-owned product candidate, LYT-100, is being advanced for the potential treatment of conditions involving inflammation and fibrosis and disorders of lymphatic flow, including lung dysfunction conditions (e.g., IPF, uILDs and Long COVID respiratory complications and related sequelae) and lymphedema.

  • Program Discovery Process by the PureTech Team
    • LYT-100 was originally developed by Auspex Pharmaceuticals, Inc. for the treatment of IPF. PureTech selected and acquired LYT-100 in July 2019 based on insights into the lymphatic system gained internally and via unpublished findings through its network of collaborators, coupled with the relationships of team members and their insights into the program previously developed at Auspex. These insights led PureTech to an initial target indication of lymphedema, and the Company also believes that LYT-100 has the potential to be evaluated in multiple fibrotic and inflammatory indications beyond its initial target indication of lymphedema, such as Long COVID respiratory complications and related sequelae, IPF, interstitial lung diseases, and FSGS.
  • Patient Need & Market Potential
    • Long COVID respiratory complications and related sequelae
      • The COVID-19 pandemic has affected tens of millions of people around the world. The virus can be deadly and there are a number of therapeutic approaches that target the acute phase of the disease. Fibrosis and inflammation are common mechanisms across several lung diseases, and there is increasing data that respiratory complications of SARS-CoV-2 (COVID-19), including shortness of breath, begin during the acute phase of illness and may persist as lung fibrosis develops. Similar respiratory complications caused by Severe Acute Respiratory Syndrome (SARS) lasted for years in many survivors. According to a research letter published in the Journal of the American Medical Association (JAMA), more than 40 percent of COVID-19 survivors assessed in an Italian study still reported shortness of breath an average of 60 days following symptom onset2. These data suggest that a significant percentage of COVID-19 survivors may be at risk for respiratory complications and other sequalae, which is a condition that is now colloquially referred to as “Long COVID.”
      • Survivors of the virus can have lung fibrosis that causes shortness of breath and other problems that could potentially last for years. In survivors, disease and invasive treatment both create fibrosis and the risk of persistently diminished lung function. Lung fibrosis can reduce the function of the lung, as observed by changes in pulmonary function tests, and can cause difficulties with activities of daily living. Clinicians are already documenting rapid progression to lung fibrosis in patients with COVID-19.
    • Lymphedema 
      • Lymphedema is a chronic condition that afflicts millions of people globally and is characterized by severe swelling in parts of the body, typically the arms or legs, due to the build-up of lymph fluid and inflammation, fibrosis and adipose deposition. Lymphedema typically progresses through multiple stages, with increased fibrosis, limb volume and tissue changes.
      • Secondary lymphedema is the most prevalent form of lymphedema. Secondary lymphedema can develop after surgery, infection or trauma, and is frequently caused by cancer, cancer treatments such as radiation and chemotherapy, trauma or infections resulting in damage to or the removal of lymph nodes.
      • Approximately one million people in the United States have lymphedema, including approximately 500,000 breast cancer survivors with secondary lymphedema. Each year, up to one in five of the more than 250,000 Americans estimated to be diagnosed with breast cancer and that undergo surgery will develop secondary lymphedema. Beyond breast cancer, lymphedema can occur in up to 15 percent of cancer survivors with malignancies ranging from melanoma and sarcoma.
      • The current standard of care for lymphedema is management, primarily with compression and physical therapy to control swelling. There are no FDA-approved drug therapies to treat lymphedema.
    • Fibrotic and inflammatory disorders
      • Fibrosis and inflammation are a common mechanism across several lung diseases. There are acute diseases with high mortality or that lead to long-term fibrosis; chronic diseases linked to a specific cause, like a virus or autoimmune disease; and diseases like IPF, where the cause is less clear. In a large percentage of these various lung conditions, there are no approved treatments that address inflammation and fibrosis of the lungs.
      • There are 140,000-250,000 people in the United States with progressive fibrosing ILDs (PF-ILDs), including IPF.
      • An estimated more than 4,500 individuals in the United States develop FSGS every year, and there are no specific treatments designed to reduce fibrosis and inflammation in this disease.

    2Carfì, A., Bernabei, R., & Landi, F. (2020). Persistent Symptoms in Patients After Acute COVID-19. Jama, 324(6), 603. doi:10.1001/jama.2020.12603

  • Innovative Approach to Solving the Problem
    • LYT-100 (deupirfenidone) is a selectively deuterated form of pirfenidone, with anti-inflammatory, antioxidant and antifibrotic properties and superior PK properties and activity compared to pirfenidone. LYT-100 shares pirfenidone’s beneficial mechanism of action but is expected to be metabolized slower and with less variability between patients compared with pirfenidone. 
    • Deuteration of pirfenidone involves substitution of specific hydrogens in a chemical structure for deuterium, a non-toxic, naturally occurring form of hydrogen. A similar modification was determined by the FDA to create a new chemical entity. Deuteration of pirfenidone improves the stability of the resulting drug, attenuates the breakdown of the drug’s active metabolite and has shown a differentiated PK profile compared to non-deuterated pirfenidone in clinical studies. PureTech believes this differentiated PK profile could enable potentially improved efficacy, less frequent dosing, improved tolerability, reduced interpatient variability in drug metabolism and reduced drug-drug interactions.
    • LYT-100 is being advanced for the potential treatment of conditions involving inflammation and fibrosis and disorders of lymphatic flow, including lung dysfunction conditions (e.g., IPF, uILDs and Long COVID respiratory complications and related sequelae) and lymphedema.
  • Intellectual Property
    • As of June 30, 2020, the LYT-100 patent portfolio includes 31 active patents acquired, and one patent application licensed from Auspex. These patents and application provide broad coverage of compositions of matter, formulations and methods of use for deuterated pirfenidone, including the LYT-100 deupirfenidone compound, comprising six issued U.S. patents, which are expected to expire in 2028, one U.S. patent application which if issued, is expected to expire in 2035, and 25 patents issued in 23 foreign jurisdictions, without taking into account any possible patent term extension or regulatory exclusivities.
    • In addition, PureTech has filed additional patent applications on deupirfenidone, including 14 pending U.S. patent applications and one international PCT application directed to the use of deuterated pirfenidone, including LYT-100 deupirfenidone, for the treatment of a range of conditions involving inflammation and fibrosis and disorders of lymphatic flow of lymphedema and other relevant disorders.
    • Any issued patents claiming priority to these applications are expected to expire in 2039 through 2041, exclusive of possible patent term adjustments or extensions or other exclusivities.
  • Milestones Achieved
    • In December 2020, PureTech announced the initiation of a Phase 2a proof-of-concept study of LYT-100 (deupirfenidone) in patients with breast cancer-related, upper limb secondary lymphedema. The randomized, placebo-controlled, Phase 2a proof-of-concept study of LYT-100 is expected to enroll up to 50 patients with breast cancer-related, upper limb secondary lymphedema. The primary endpoints for this trial will be safety and tolerability, with secondary clinical efficacy and biomarker endpoints. The study is not powered to evaluate statistical significance compared to placebo, but PureTech expects to use data emerging from the trial to shape future clinical protocols, including selection of potential future efficacy study endpoints.
    • In December 2020, PureTech announced the initiation of its global, Phase 2 trial of LYT-100 in Long COVID respiratory complications and related sequelae. The global, randomized, double-blind, placebo-controlled Phase 2 trial is designed to evaluate the efficacy, safety and tolerability of LYT-100 in adults with post-acute COVID-19 respiratory complications. The primary endpoint of the trial will be the six-minute walk test distance. Secondary endpoints, including pharmacokinetics, inflammatory biomarkers, imaging and patient-reported outcomes including dyspnea and the 36-Item Short Form Health Survey, will also be evaluated.
    • In November 2020, PureTech announced the completion of a Phase 1 multiple ascending dose and food effect study for LYT-100. The study demonstrated favorable proof-of-concept for LYT-100’s tolerability and pharmacokinetic (PK) profile, which will also enable twice-a-day (BID) dosing of LYT-100 in future studies.
    • In July 2019, PureTech acquired LYT-100 from Auspex. Auspex was a leader in deuteration chemistry and was acquired by Teva Pharmaceutical Industries in 2015.
    • LYT-100 was previously studied in a single dose crossover Phase 1 clinical trial of 24 healthy volunteers to assess safety and PK. These results demonstrate that LYT-100 displays improved PK relative to pirfenidone and suggest the possibility of twice daily dosing of LYT-100 in patients with lymphedema. In addition, LYT-100 was well-tolerated and there were no SAEs observed in the Phase 1 clinical trial of healthy volunteers.
  • Expected Milestones
    • PureTech expects results from its Phase 2a proof-of-concept study of LYT-100 (deupirfenidone) in patients with breast cancer-related, upper limb secondary lymphedema in the fourth quarter of 2021. 
    • PureTech expects results from its Phase 2 trial of LYT-100 in Long COVID respiratory complications and related sequelae in the second half of 2021.
    • PureTech is also advancing LYT-100 for the treatment of IPF and planning registration-enabling studies.

PureTech's lead wholly-owned product candidate, LYT-100, demonstrated favorable proof-of-concept for its tolerability and pharmacokinetic profile in a Phase 1 multiple ascending dose and food effect study. It is being advanced for the potential treatment of conditions involving inflammation and fibrosis and disorders of lymphatic flow. These include lung dysfunction conditions (e.g., IPF, unclassifiable interstitial lung diseases, Long COVID respiratory complications and related sequelae) and lymphedema. 


Advancing LYT-100 for treatment of Long COVID respiratory complications and related sequalae

The potential for fibrosis-mediated lung damage and the unprecedented scale of the current pandemic creates an enormous public health challenge: some patients who have recovered from the acute symptoms of COVID-19 have persistent pulmonary dysfunction. New therapeutic options are needed to address the underlying inflammation and fibrotic mechanisms that lead to respiratory complications that persist following the resolution of COVID-19 infection.



Lymphedema: A feedback loop between inflammation and fibrosis