Galecto Biotech is focused on developing treatments for fibrotic diseases by targeting galectins, proteins involved in fibrosis. They have developed TD139, a potent and specific galectin-3 inhibitor, as a treatment for idiopathic pulmonary fibrosis (IPF). Preclinical studies in mice showed TD139 reduced fibrosis when delivered via inhalation after bleomycin-induced lung injury. A first-in-human study of inhaled TD139 found it was well tolerated with no dose-limiting toxicities. Galecto is currently conducting a Phase II clinical trial testing multiple doses of inhaled TD139 in IPF patients to evaluate safety and efficacy markers.

1. Kent Hoover, Isabel Lippincott, Angel Pichardo, Katherine Anne
Rebholz, Beau Smith, Katrina Wiesner
Galecto Biotech

2. ● Founded Nov 2011 by world leading Galectin and Fibrosis experts
● Focus on Galectin Modulation
◦ Galectins have been shown to be involved in several pathological
conditions
◦ Founders have world class insight into Galectin biology and
pharmacology with dozens of publications
● Target Indications: Fibrotic Diseases
◦ IPF – a >$500 M IPF market opportunity with clear regulatory &
clinical path
● Clinical development
◦ IPF: First Human Dose completed Sept. 2014
◦ Phase IIb in 24 IPF patients ongoing
◦ Three issued US composition of matter patents
Summary – Galecto Biotech

3. ● IPF is a progressive,
irreversible, ultimately
fatal lung disease
characterized by decline
in lung function due to
scarring
◦ Respiratory failure
◦ Median survival of 2 - 5
years
◦ Cause is unknown, but
Galectin-3 is upregulated in
the lung tissue of IPF
patients.
Idiopathic Pulmonary Fibrosis

4. ● US incidence of IPF: ~30,000/yr
● US prevalence: ~100,000, EU: ~120,000
◦ Increasing incidence and IPF-related deaths worldwide
● Most patients are ≥ 50 years-old at diagnosis
◦ Males more frequently affected than females
◦ In approx 10 % of cases there is a family history of IPF
IPF, an Orphan Indication

5. ● Pirfinedone (Esbriet; Roche)
◦ Approved in EU and US
◦ Dose limiting side effects – upper GI symptoms and
skin sensitivity to light
● Nintedanib (BI)
◦ Tyrosine kinase inhibitor
◦ Just approved in EU and US
◦ Dose limiting side effects – diarrhea (> 60 %)
● Both only demonstrated to slow disease progression
IPF Drugs on Market

6. Lectins: Sugar binding proteins:
● Intra and Extracellular, often membrane bound.
● Mediate cellular, carbohydrate, and protein recognition
● Involved in bacterial and viral binding
● Can be toxic
Galectins: Non-Membrane bound
● Bind beta-galactoside sugars
○ Found in Cytosol, nucleus, ECM, and Circulation
○ Upregulation of Galectin-3 has been linked to fibrosis in the
lungs, kidneys and liver.
Galectins and IPF

7. ● Affects signaling of cell
surface receptors, including
TGF-ß
● Galecto has developed a
series of potent and specific
Galectin-3 inhibitors,
including TD139
TD139 Target: Galectin-3
Galectin-3
TD139

8. ● Study design:
○ Mice were treated with
bleomycin intratracheally day 0
○ TD139 was instilled into the lungs
on days 18, 20, 22 and 24
■ – well after the inflammation had
ceased
○ The level of fibrosis was
evaluated at day 26
■ Total collagen
■ Fibrosis score (histological)
■ β−catenin activation
In Vivo Study of TD139
A Small Molecule Inhaled Galectin-3 Antagonist

9. ● First in man study
completed, enabling
toxicology and safety
studies
◦ No dose limiting toxicity
observed
◦ 28 day studies conducted
◦ Highest dose tested 30
mg/kg in mice – 8 mg/kg
in dogs
Dry Powder Inhaled TD139
Plastiape monohaler

10. ● Study design
◦ Combined healthy volunteer and patient study
● Healthy volunteer study completed:
◦ 6 dose groups (0.15, 1.5, 3, 10, 20 and 50 mg)
◦ 4 active, 2 placebo in each group
● Results
◦ Mild adverse effects only (cough & headache)
◦ All lab and other clinical parameters satisfactory
◦ Plastiape inhaler performing well
Clinical Data in Healthy Volunteers

11. ● 20-24 patients in 2-3 dose groups
● Primary endpoint: Safety
● Secondary endpoints: Markers of efficacy
● Three centers in the UK
● Planned duration: Mar 2015 to Jun 2016
Patient Study
Daily Treatment for 14 DaysDay0
Day14
Examinations,
Including lung lavage
Examinations,
Including lung lavage
Daily inhalation of TD139
0.3-10 mg

12. ● Galectin-3 has been shown to play a central role in
fibrosis in many organs
● Development of an orally active Gal-3 inhibitor would
open up a plethora of new opportunities
● We have also identified new gal-3 inhibitors with
increased bioavailability
● Phase IIa trials for TD139 ending in June 2016
● Ca$h Money
Moving Forward...