TERT Mrna for Telomere Extension to Treat Fatal Diseases and Aging

TERT mRNA for telomere extension to treat fatal diseases and aging

Aging or disease

TERT mRNA

• Aging is the strongest risk factor for all age- related diseases

• Telomeres are a cellular Deaths per 100,000per Deaths aging clock Age:

• Telomere extension From: The Milbank Quarterly, Vol. 80 No. 1, 2002, from US 1997 Vital Statistics resets the aging clock

2 Prepared for Rejuvenation Tech Investors The road to healthspan extension

Market Liver $30B Liver Cirrhosis, Alcoholic Hepatitis

Lung • Safety & efficacy data $10B Interstitial Lung Disease including IPF • Capital Blood $10B Cytopenia, Neutropenia

Whole body

Clinical Trial Endpoints: • Improved function (6 months) $1T+ AGING • Delayed all-cause mortality (2 years) • Longer healthspan (Phase IV)

3 Prepared for Rejuvenation Tech Investors mRNA therapies have come of age

Jan. 2020 Market caps Jan. 2021 • 2020 was the year mRNA worked Moderna $65B • $100B in value created $6B • We invented a way to reset the aging clock using mRNA BioNTech $27B

• In 2020 we achieved proof-of- concept in mice $7B Translate Bio $1.9B • Series A to gain IND clearance for first-in-human studies $0.4B

4 Prepared for Rejuvenation Tech Investors Summary

• TERT mRNA: our patented method to extend telomeres

• One dose reverses a decade of telomere shortening

• Lead indications: fatal diseases of liver and lung

• TERT mRNA extends survival by 42% and reduces liver fibrosis by 25% in mice

• First FDA meeting Q2 2021

5 Prepared for Rejuvenation Tech Investors Short telomeres are deadly

• Telomeres protect chromosome tips but shorten each time cells divide

• When telomeres become too short cells can’t divide

• If cells can divide, patients stay alive If cells can’t divide, patients die

Prepared for Rejuvenation Tech Investors TERT mRNA enables cells to divide more

Human cell growth curves (in vitro)

100 Treatment 4 3 + 1 90 treatments 80 3 treatments 2 treatments 70 Treatments 1 treatment 60 1-3 50 40 TERT mRNA increases the proliferative capacity of cells

30 Population doubling doubling (n) Population 20 10 0 0 20 40 60 80 100 120 140 160 180 Day 7 Prepared for Rejuvenation Tech Investors Reset cellular clock with TERT mRNA

Telomere shortening mechanism remains intact Length at birth Telomere length Telomere catastrophe

TERT mRNA TERT mRNA Dosing Schedule

Telomere extension rate

Disease risk Time (years) 8 Prepared for Rejuvenation Tech Investors How TERT mRNA extends telomeres

5’ UTR Poly-A Tail Cap

TERT mRNA 3’ UTR Delivery by lipid nanoparticles

TERT mRNA Translation Functional TERT protein

Telomere extension Modified Nucleosides Cell

Cell 9 Prepared for Rejuvenation Tech Investors TERT mRNA advantages

5’ UTR Poly-A Tail TERT mRNA avoids the problems of other Cap approaches: 3’ UTR ✓ Safe TERT DNA gene therapy • Genomic integration, continuous TERT ✓ Transient expression • Immortalizing, unsafe ✓ Fast-acting • AAV causes genomic integration (Kaeppel, 2013) in tens of millions of cells per dose ✓ Telomere-specific • Companies: Telocyte, Libella

✓ Non-integrating Small molecule TERT activators • Screens since 1998 ✓ Non-immortalizing • Slow and ineffective • Chronic dosing, chronic activation ✓ Hypoimmunogenic • Companies: Sierra Sciences, TA Sciences

✓ Avoids the problems that Other genes • Transient expression of zscan4 for two days continue to stymie other generates cancer stem cells (Portney, 2020) valiant efforts • Company: Elixirgen

10 Prepared for Rejuvenation Tech Investors Pipeline

INDICATION RESEARCH IN VIVO EFFICACY IND-ENABLING PHASE I

Aging AGING Liver cirrhosis* TERT-101 2022 One formulation for

LIVER Alcoholic hepatitis TERT-101 2022 multiple indications

Pulmonary fibrosis* TERT-201 LUNG Hematopoietic stem cells

Mesenchymal

stem cells EX EX VIVO

* Patients with TERT mutations, subpopulation available

11 Prepared for Rejuvenation Tech Investors Target milestones

Months post close

0 6 12 18 24 FDA INTERACT (liver) Pre-IND meeting (liver) IND clearance (liver)

Pre-IND meeting (lung)