LYT-100

Our programs
Discovery
Preclinical
Phase 1
Phase 2
Phase 3
LYT-100
Deupirfenidone
Lymphatic Flow Disorders, Incl. Lymphedema
Initiation of POC study in 2020

1

Lymphatic Flow Disorders, Incl. Lymphedema

~1M

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
Initiation of POC study in 2020

1

Other Fibrotic & Inflammatory Disorders

~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
A potent anti-inflammatory and anti-fibrotic oral molecule 

PureTech is developing LYT-100, a clinical-stage product candidate for the potential treatment of 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).

 

We are advancing a broad pipeline of programs to treat cognitive deficiency and improve symptoms associated with medical conditions across neurology and psychiatry, including attention-deficit hyperactivity disorder (ADHD), major depressive disorder (MDD), autism spectrum disorder (ASD), multiple sclerosis (MS) and various other neuroinflammatory diseases. We are also developing associated clinical monitors and measurement-based care applications. Our lead, patented technology platform is exclusively licensed from the lab of Dr. Adam Gazzaley at the University of California, San Francisco (UCSF), and augmented by proprietary adaptive algorithms developed by our team.

  • Program Discovery Process by the PureTech Team
    • PureTech acquired LYT-100 in July 2019 based on the company’s insights into immunology and lymphatic biology coupled with knowledge of unpublished findings from academic collaborators and awareness of data generated by Auspex Pharmaceuticals (Auspex). LYT-100 was originally developed by Auspex, which is now a wholly-owned subsidiary of Teva Pharmaceuticals, for the treatment of idiopathic pulmonary fibrosis (IPF) and other fibrotic conditions. LYT-100 has demonstrated potent anti-fibrotic and antiinflammatory activity with significant reduction in IL-6 and TNF-alpha levels in preclinical disease models including lymphedema, and – importantly – it has been evaluated in human clinical safety studies. PureTech believes LYT-100, if successfully developed and approved, could become a promising treatment for a range of these serious fibrotic and inflammatory conditions, with an initial focus on lymphedema.
  • Patient Need & Market Potential
    • Lymphatic flow disorders
      • Lymphedema is a chronic and progressive disorder that 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 can cause loss of range of motion and function in the affected limb, disfigurement and pain. Lymphedema typically progresses through multiple stages, with increased fibrosis and limb volume and tissue changes.
      • Secondary lymphedema is the most prevalent form of lymphedema, and it can develop after surgery, infection or trauma and is frequently caused by cancer or cancer treatments.
      • 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 who 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 to sarcoma.
      • The standard of care is management, primarily by compression and physical therapy to control swelling. There are currently no FDA approved drug therapies to treat lymphedema.
    • Fibrotic and inflammatory disorders
      • To date, there are more than five million documented cases of COVID-19 infections worldwide. Emerging data suggests that a high proportion of these patients are at risk of impaired lung function and fibrosis after recovery, highlighting the widespread need for therapeutics to address the longer-term sequalae of COVID-19.
      • Interstitial lung disease (ILD) includes chronic fibrosing diseases like IPF, as well as acute forms like acute exacerbations of IPF and acute interstitial pneumonia, which have high mortality and limited therapeutic options. These acute ILDs can be triggered by viral infections, including coronaviruses such as Middle East Respiratory Syndrome (MERS) and Severe Acute Respiratory Syndrome (SARS). Long-term pulmonary fibrosis and reduced respiratory function similar to chronic ILD has been observed in SARS and MERS. A drug therapy with anti-inflammatory and anti-fibrotic activity may have the potential to reduce the symptoms of acute interstitial pneumonia as well as treat the progressive lung damage that can end up affecting survivors of the disease.
      • Apart from the direct destruction of lung function caused by infections, severe and prolonged inflammatory reactions mediated by numerous cytokines, including TNF-alpha and IL-6, are also a characteristic feature. Therefore, treatment strategies should include not only inhibitors of virus proliferation but also include therapies like LYT-100 that suppress pro-inflammatory mediators that can damage lung tissue. 
  • Innovative Approach to Solving the Problem
    • LYT-100, or deupirfenidone, is an oral deuterium-containing analogue of pirfenidone. LYT-100 retains the same intrinsic pharmacology of pirfenidone, while potentially improving its tolerability and safety profile. LYT-100 has shown a differentiated and superior pharmacokinetic (PK) profile compared to pirfenidone in human studies, and it would be classified as a New Chemical Entity. Pirfenidone is an orally-administered, small molecule currently approved for the treatment of IPF, and it was recently given Breakthrough Therapy designation from the FDA for uILD. Pirfenidone has also demonstrated significant activity in lymphedema resolution in preclinical models, and it also has documented activity in patients with rare kidney disorders, such as focal segmental glomerulosclerosis (FSGS), as well as radiation-induced fibrosis and a number of other fibrotic conditions.
    • LYT-100 is being developed for the potential treatment of a range of conditions involving fibrosis, inflammation, and impaired lymphatic flow. These conditions include lymphedema, IPF, interstitial pneumonias, uILD and other ILD, radiation-induced fibrosis and FSGS.
    • PureTech has GMP supply of LYT-100 for its ongoing Phase 1, multiple ascending dose study, which is designed to evaluate the safety, tolerability and PK of LYT-100. PureTech has increased its clinical supply and is planning to advance LYT-100 for the treatment of breast cancer-related, upper limb secondary lymphedema and other fibrotic and inflammatory disorders. 
  • Intellectual Property
    • As of 31 December 2019, 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 two 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 lymphedema and other relevant disorders.
    • Any issued patents claiming priority to these applications are expected to expire in 2039 through 2040, exclusive of possible patent term adjustments or extensions or other exclusivities.
  • Milestones Achieved
    • In March 2020, PureTech initiated a Phase 1 multiple ascending dose study in healthy volunteers.
    • In July 2019, PureTech acquired LYT-100 from Auspex, a leader in deuteration, which was acquired by Teva Pharmaceutical Industries in 2015.
    • LYT-100 was 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 serious adverse events observed in the Phase 1 clinical trial of healthy volunteers. 
  • Expected Milestones
    • PureTech expects results from the multiple ascending dose and food effect study in 2020, which, if successful, may enable the initiation of a proof-of-concept study in people with breast cancer-related, upper limb secondary lymphedema in 2020, as well as additional studies in people with other fibrotic and inflammatory conditions.
    • PureTech plans to initiate a trial in Q3 2020 evaluating LYT-100 as a potential treatment for serious respiratory complications, including inflammation and fibrosis, that persist following the resolution of SARS-CoV-2 (COVID-19). Topline results are expected in mid-2021.
    • PureTech is evaluating additional inflammatory and fibrotic conditions that could potentially be addressed with LYT-100.

PureTech’s most advanced wholly-owned program, LYT-100, is currently being evaluated in a Phase 1 multiple ascending dose study. LYT-100 has the potential to treat a range of serious conditions related to fibrosis, inflammation and impaired lymphatic flow, including lymphedema, a condition that affects approximately one million people in the United States and has no FDA-approved drug treatment. PureTech also plans to advance LYT-100 as a potential treatment for serious respiratory complications that persist following the resolution of SARS-CoV-2 (COVID-19) infection and is evaluating additional inflammatory and fibrotic conditions that could potentially be addressed with LYT-100.


Advancing LYT-100 for treatment of serious respiratory complications that persist following resolution of COVID-19 infection

Many interstitial lung diseases are caused by inflammation and fibrosis, which can result in impaired lung function. This dysfunction has been documented in COVID-19 patients, including those who have recovered. PureTech plans to advance its wholly-owned clinical candidate, LYT-100, in a global, randomized, placebo-controlled trial as a potential therapeutic option.



This figure depicts the feedback loop between inflammation and fibrosis-driven lymphedema

Panel A shows lymphedema skin biopsy samples from lymphedematous and normal limbs of patients. As shown in Panel B, lymphedema skin biopsy samples from lymphedematous and normal limbs of patients show increased intracellular TGF-β1 staining in immunohistochemical staining.



LYT-100 has been studied in a single dose crossover study in healthy volunteers and is currently being evaluated in a Phase 1 multiple ascending dose study

Preclinical

LYT-100 showed anti-fibrotic and anti‑inflammatory activity which may break the feedback loop in lymphedema.


Clinical

LYT-100 showed favorable PK to pirfenidone.


Planned

LYT-100 entered a Phase 1 trial in 2020, and two patient proof-of-concepts are expected to begin in 2020.

LYT-100 is expected to have:

  • Potential lower dose and less frequent dosing
  • Potential better safety profile

Advised by the world's leading lymphedema experts: