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First-in-class small-molecule anti-fibrotic and anti-cancer agents January 2021
Forward-looking statements This presentation contains forward-looking statements that involve substantial risks and uncertainties. All statements, other than statements of historical facts, contained in this presentation, including statements regarding Galecto, Inc.'s (the "Company") strategy, future operations, future financial position, projected costs, prospects, plans, and objectives of management, are forward-looking statements. The words anticipate,'' believe,'' continue,'' could,'' estimate,'' expect,'' intend,'' may,'' plan,'' potential,'' predict,'' project,'' target,'' should,'' would,'' and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. For such statements, we claim the protection of the Private Securities Litigation Reform Act of 1995. The Company may not actually achieve the plans, intentions, or expectations disclosed in these forward-looking statements, and you should not place undue reliance on these forward-looking statements. Actual results or events could differ materially from the plans, intentions and expectations disclosed in these forward-looking statements. Factors that could cause actual results to differ materially from such statements include, without limitation: Drug development is expensive, time consuming, uncertain and susceptible to change, interruption, delay or termination; the timing and outcome of research, development and regulatory review and feedback is uncertain; we expect to need additional funds to advance all of our programs, and you and others may not agree with the manner in which we allocate our resources; the amount of our future losses is uncertain and could cause our stock price to fluctuate or decline; topline data may not accurately reflect the complete results of a particle study or trial; results of clinical trials and other studies are subject to different interpretation and may not be predictive of future results; new data may be unexpected or unfavorable; GB0139, GB1211, GB2064 or other drug candidate may not advance in development or be approve for marketing; clinal trial and other studies may not proceed at the time or in the manner expected or at all; enrolling patients in our ongoing and intended clinical trials is competitive and challenging; the duration and severity of the ongoing coronavirus disease (COVID-19) pandemic, including but not limited to the impact on our clinical and other operations, the operations of our suppliers, others and the capital markets, which in each case remains uncertain; clinical and nonclinical data is voluminous and detailed, and regulatory agency may interpret or weigh the importance of data differently and reach different conclusions than we or others, request additional information, have additional recommendations or change their guidance or requirements; data and information related to our program may not meet regulatory requirements or otherwise be sufficient for further development at all or on our projected timeline; other risks related to developing, seeking regulatory approval of and commercializing drugs, including regulatory, manufacturing, supply and marketing issues and drug availability; our and third parties' intellectual property rights; competition; reimbursement and pricing decisions; risk relating to relying on third parties; product liability and other litigation; and legislation and regulations. Additional factors that could cause results to differ materially from those stated or implied by our forward-looking statements are disclosed in our Securities and Exchange Commission (SEC) filings, including under the headings "Risk Factors." In addition, the forward-looking statements included in this presentation represent the Company's views as of the date of this presentation. The Company anticipates that subsequent events and developments will cause its views to change. However, while the Company may elect to update these forward-looking statements at some point in the future, it specifically disclaims any obligation to do so. These forward-looking statements should not be relied upon as representing the Company's views as of any date subsequent to the date of this presentation.
Investment Highlights 3
start Potentially registrational in US and EU Unique Pipeline Targeting Fibrosis and Cancer 2022 2022 2022 2022 4
Galectin-3 and LOXL2: Targeting Serious Fibrotic Diseases Through Two Different Mechanisms of Action 5 GB0139 and GB1211
(Galectin-3 inhibitors) GB2064
(LOXL2 Inhibitor) Feedback loop Galectin-3 activates macrophages and recruits and activates all key cell types in fibrosis LOXL2 drives cross-linking of collagen, forming the backbone of fibrosis
GB0139: Inhaled Galectin-3 Inhibitor for IPF 6
Approximately 100K patients in US
IPF is a progressive, irreversible, ultimately fatal lung disease characterized by decline in lung function (as measured by FVC)
Lung tissue scars and becomes non-functional
Median survival of 2-5 years
Death caused by respiratory failure
Unknown cause IPF is a Large Orphan Indication with Suboptimal Solutions 7 Only two approved drugs to slow disease progression: Pirfenidone and Nintedanib
Neither has been associated with improvements in overall survival
Both have significant side-effects that limit compliance and usage
Due to side effects, less than 50% of patients on treatment
Despite dose-limiting side effects, sales of pirfenidone and nintedanib in 2019 exceeded $2.8B in the aggregate
Disease Overview Limited Treatment Options
GB0139 Well tolerated in clinical trials and long-term toxicology studies to date
Existing therapies marred by significant side effects leading to approximately 50% discontinuations Unique and pluripotent MoA
GB0139 inhibits fibrosis by targeting macrophages, fibroblasts, and epithelial cells GB0139 reduced macrophage galectin-3 levels in lungs of IPF patients
Dose-response effects on several fibrosis plasma biomarkers
No other therapy in development has demonstrated similar consistent effects Inhaled therapy via generic inhaler delivers therapy directly to target tissue with low systemic exposure
Competing clinical development candidates given intravenously, subcutaneously and orally Superior delivery Pluripotent MoA Well Tolerated Confirmed Target Engagement GB0139: Inhalable, Once-Daily Treatment for IPF
Potential for Accelerated Approval 8
Phase 1 Trial Design
6 dose groups (0.15, 1.5, 3, 10, 20 and 50 mg)
4 active patients and 2 placebos in each group
Key Phase 1 SAD Study Results
Highly reproducible pharmacokinetic (PK) profile and dose-dependent exposure
Mild adverse events (AE) only (cough & headache)
All lab and other clinical parameters satisfactory
Generic inhaler performing well
GB0139: Results of Phase 1 SAD Study 9
24 patients in 3 dose groups
Double-blind, placebo-controlled, multicenter
Doses: 0.3, 3 and 10 mg per day
5 active patients and 3 placebos per group
Four centers in the UK
All patients completed 2 week dosing as planned
Evaluable bronchoalveolar lavages (BALs) obtained for all 48 bronchoscopies
GB0139: Phase 2a Patient Study in IPF Patients 10
GB0139: Phase 2a Result - Bioavailability & Target Engagement in IPF Patients 11 Exceptionally Consistent PK Data in IPF Patients GB0139 Reaches the Alveolar Macrophages Deep within Lung Extracellular Gal-3 Levels
Alveolar Macrophages GB0139 Concentration in Alveolar Macrophages Induces Profound Reduction of Gal-3 Levels on Alveolar Macs
GB0139: Phase 2a Study Showed Consistent, Dose-Dependent Effects on Highly Relevant Fibrosis Biomarkers 12 Biomarkers associated with IPF disease severity and progression had biggest impact
Biomarker effects cited by EMA as clinically relevant in IPF patients and basis for ODD
BAL fluid and plasma correlation indicates GB0139 directly impacts lung function PDGF-BB PAI-1 Galectin-3 CCL18 YKL-40
Comparison: GB0139 MoA to alternative programs 13
GB0139: Phase 2b IPF Study In Progress Randomized, placebo controlled 52 week study
450 IPF patients in 3 arms
First-patient, first-visit in Q1 2019
Expected completion in mid 2022
Primary outcome measure:
Annualised rate of FVC decline over 52 weeks
Study is also powered to see an effect in the patients on neither pirfenidone nor nintedanib
Key secondary outcomes:
Safety, DLCO , 6 minute walk test, Quality of Life
14 * DLCO - Diffusing Capacity for Carbon Monoxide (*)
Ground-breaking novel treatment of IPF, an orphan disease with poorly tolerated treatments
Inhaled, delivered directly to the site of active lung destruction
Well tolerated in trials to date
Reaches the target cell in the lung at high concentrations
Causes a dose-related reduction in cell surface galectin-3 deep within patient lungs
Promising biomarker trends observed in Phase 2a study - validated by EMA as clinically relevant in IPF patients and basis for ODD
Phase 2b study underway - FDA and Medicines and Healthcare Products Regulatory Agency (MHRA) approved design
Conditional approval possible after Phase 2b completion GB0139: Inhaled Galectin-3 Inhibitor Summary 15
GB2064: LOXL2 Inhibitor for Myelofibrosis and Other Fibrotic Diseases 16
GB2064: Oral LOXL2 Inhibitor in Myelofibrosis GB2064 (previously PAT-1251)
A small-molecule inhibiting LOXL2, an enzyme that catabolizes the formation of lysine cross-linking in fibrillar collagens
Potentially disease modifying
Opportunity in multiple fibrotic indications
Orphan indication: 16,000 - 18,500 patients in US
Current therapies (JAK inhibitors) are not disease modifying
Large market - Incyte's Jakafi achieved $1.7bn in 2019 sales
17 Overview and Treatment Opportunity LOX Family Gene Expression in Myelofibrosis Stromal Cells LOXL2 paralogue most upregulated in active myelofibrosis
GB2064: Demonstrated In Vitro Inhibition of LOXL2 GB2064 is a small-molecule inhibitor of the LOXL2 catalytic site, not an antibody approach
GB2064 therefore has the potential to avoid the in vivo target low tissue penetration and target engagement encountered by Gilead's simtuzumab
GB2064's superior efficacy to simtuzumab has been observed in cell-based assays and preclinical models 18 GB2064 fully inhibits LOXL2 activity using a variety of substrates GB2064 (Galecto)
Study to be led by Professor Srdan Verstovsek, MD Anderson
Single arm open label study, allowing real time read of safety and activity
Patients who are ineligible for JAK-inhibitors or who do not tolerate JAKi
bone marrow general histology and fibrosis
PK to show drug levels in target tissue
imaging for spleen and liver volume
MYLOX-1: GB2064 in Myelofibrosis 19
GB2064: Phase 2a in Myelofibrosis Summary Ample evidence for central role of LOXL2 in fibrosis
GB2064 potently inhibits LOXL2 and shows antifibrotic activity in numerous models
Upcoming Phase 2a could generate both target engagement and efficacy data in the same study as repeated biopsies are already standard practice
Opportunity for both orphan designation and fast track following data in this indication
IND approved October 2020, and Phase 2a to start in coming months
Phase 1 SAD/MAD study already completed
Chronic toxicology studies completed
Robust efficacy in lung, liver and kidney models
GB1211: Oral Galectin-3 Inhibitor for Cancer and Fibrosis 21
22 Galecto's Oral Galectin-3 Inhibitors Galectin-3 is a very attractive target for a series of currently poorly treated indications, including many cancer types and fibrosis
Galecto is pioneering galectin field and has developed a series of orally active, specific and potent inhibitors of galectin-3
These bind to the carbohydrate recognition domain and inhibit the galectin-3 related effects on several key cell types
The lead compound, GB1211, reduces fibrosis and cancer growth in several different animal models
Well tolerated in IND-enabling studies