LYT-100

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Discovery
Preclinical
Phase 1
Phase 2
Phase 3
LYT-100
Deupirfenidone
Lymphatic flow disorders, incl. lymphedema
Readout from Phase 1 MAD study & initiation of POC study in H2 2020

1

Lymphatic flow disorders, incl. lymphedema

~1M

Product candidate 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.

LYT-100
Deupirfenidone
Long COVID1 respiratory complications & related sequelae
Initiation of Phase 2 study in H2 2020

1

Long COVID respiratory complications & related sequelae


Product candidate for a range of conditions involving fibrosis, inflammation and impaired lymphatic flow, including lymphedema, idiopathic pulmonary fibrosis (IPF), interstitial pneumonias, unclassifiable interstitial lung disease (uILD) and other interstitial lung disease (ILD), radiation-induced fibrosis and focal segmental glomerulosclerosis (FSGS).
LYT-100
Deupirfenidone
Other fibrotic & inflammatory disorders, such as IPF

1

Other fibrotic & inflammatory disorders, such as IPF

~130K (IPF or uILD)


Product candidate for a range of conditions involving fibrosis, inflammation and impaired lymphatic flow, including lymphedema, idiopathic pulmonary fibrosis (IPF), interstitial pneumonias, unclassifiable interstitial lung disease (uILD) and other interstitial lung disease (ILD), radiation-induced fibrosis and focal segmental glomerulosclerosis (FSGS).

Phase completedPhase in progress

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selected and acquired LYT-100 in July 2019 based on insights into the lymphatic system gained internally and via unpublished findings through its network of collaborators, coupled with the relationships of team members and their insights into the program previously developed at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. There is increasing data around the longer-term complications of COVID-19, referred to as Long COVID, including preliminary data regarding respiratory issues that persist. 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 currently no approved drug therapies that can treat the underlying causes of 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 approximately 130,000 people living with IPF or uILD in the United States.
      • 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.
  • 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 March 2020, PureTech announced the initiation of a multiple ascending dose study of LYT-100 to evaluate the safety, tolerability and PK profile of LYT-100 in healthy volunteers.
    • In May 2020, PureTech announced plans for a global, randomized, placebo-controlled Phase 2 trial to evaluate the efficacy, safety and tolerability of LYT-100 in non-critical COVID-19 patients with respiratory complications.
    • 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 the multiple ascending dose study of LYT-100 to evaluate the safety, tolerability and PK profile of LYT-100 in healthy volunteers in the second half of 2020.
    • A subsequent POC trial in people with breast cancer-related, upper limb secondary lymphedema is expected to begin in the second half of 2020 with topline results expected in the second half of 2021.
    • PureTech plans to initiate a global, randomized, placebo-controlled Phase 2 trial to evaluate the efficacy, safety and tolerability of LYT-100 in non-critical COVID-19 patients with respiratory complications  in the second half of 2020, with topline results expected in second half of 2021.
    • PureTech plans to explore applications of LYT-100 where the anti-inflammatory and anti-fibrotic activity of pirfenidone has demonstrated clinical and preclinical activity, including IPF where pirfenidone is already approved for use, and other ILDs.

PureTech's lead wholly-owned product candidate, LYT-100, is currently being evaluated in a multiple ascending dose Phase 1 clinical trial. LYT-100 has the potential to be evaluated in multiple fibrotic and inflammatory indications beyond the Company's initial target indication of lymphedema, such as Long COVID respiratory complications and related sequelae, IPF, interstitial lung diseases, and FSGS. PureTech also plans to explore applications of LYT-100 where the anti-inflammatory and anti-fibrotic activity of pirfenidone has demonstrated clinical and preclinical activity, including IPF where pirfenidone is already approved for use, and other ILDs.


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