www.sareum.co.uk

Dr Tim Mitchell, CEO & Co-Founder

Next-generation TYK2/JAK1 Immunotherapeutics for

Autoimmune Diseases and Cancer (and Covid-19)

BioTrinity, April 2020

Specialists in Small Molecule Drug Development

www.sareum.co.uk 2

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www.sareum.co.uk

Psoriasis, RA, lupus, IBD, MS

T-ALL, ccRCC, immunotherapy

AML, ALL

Solid tumours

Anogenital

Prostate

Lung, colon,

Advancing our Pipeline

3

AML: Acute Myeloid Leukaemia; RA: Rheumatoid Arthritis; ALL: Acute Lymphoblastic Leukaemia; IBD: Inflammatory Bowel Disease;

T-ALL: T-cell Acute Lymphoblastic Leukaemia; MS: Multiple Sclerosis; ccRCC – clear cell Renal (kidney) Cell Carcinoma; PARP - Poly ADP Ribose Polymerase;

ADP – Adenosine Di-Phosphate

• 100% focused on development of our proprietary TYK2/JAK1 inhibitors

Autoimmune

diseases

Cancer

Leukaemia

Monotherapy

Low dose gemcitabine

(LDG) combination

PARP inhibitor

combination

Immunotherapy combination

TYK2/JAK1

FLT3+Aurora

Chk1

SDC-1801

Licensed to China-based

specialty pharma

SDC-1802

SRA737

Clinical

Phase IITarget

Lead

optimisation

Candidate

selectionPreclinical

Clinical

Phase IPotential indications

Proprietary

Programmes

Partnered

Programmes

www.sareum.co.uk

TYK2/JAK Inhibitors are Emerging Targets of

Increasing Pharma Interest

• The TYK/JAK cell signalling family (TYK2, JAK1, JAK2, JAK3) is important

for maintaining healthy immune system

• Strong clinical validation (BMS, Pfizer) for TYK2 and TYK2/JAK1 in

psoriasis, but with room for improvement

• Late-stage clinical trials of TYK2 and TYK2/JAK1 inhibitors (BMS, Pfizer)

ongoing for lupus, UC, Crohn’s, vitiligo – readouts in 2020

4

www.sareum.co.uk

JAK Inhibition on Signalling of Key

Immunoregulatory Cytokines

5

O’Shea J, et al. Immunity 2012;36(4);542-550

Therapeutic

opportunities

RA,

Resistance to I/O,

Viral/bacterial

pneumonia

Psoriasis, IBD, Lupus,

Resistance to I/O,

Viral/bacterial

pneumonia

Psoriasis, IBD, RA, LupusRA, respiratory failure

from viral infections

JAK2 and JAK3 inhibition associated with the FDA “black box” warnings for serious infections, lymphoma and thrombosis issued to

JAK1/JAK3 inhibitor Xeljanz (tofacitinib) and JAK1/JAK2 inhibitor Olumiant (baricitinib)

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We are Focused on Selective, Potent

TYK2/JAK1 Inhibitors

Significant clear opportunities available to Sareum

• No marketed products with selectivity for TYK2 – important for differentiation

• No TYK2 inhibitors in clinical trials for cancer – first-in-class opportunity

SDC-1801 and SDC-1802

• Potent & selective inhibitors of TYK2 and JAK1 kinases

• Oral twice-daily dosing in mice, potential for once-daily dosing in humans

• Favourable selectivity profile vs JAK2 and JAK3 kinases (cf tofacitinib, baricitinib,

ruxolitinib)

Development Strategy

• Internal focus on completing IND-enabling studies on SDC-1801 and SDC-1802

• Seek development partners for commercial licences at late-preclinical or early clinical stage

6

www.sareum.co.uk

SDC-1801: Targeting Autoimmune Diseases

• Good efficacy in disease models of psoriasis and rheumatoid arthritis

• Maximum tolerated dose not reached at 30x dose used in efficacy studies

• Dose-ranging studies underway

• Synthetic route developed for large-scale manufacturing for toxicology and clinical studies

7

Rheumatoid arthritis model

SDC-1801 dosed orally (5, 10 & 20 mg/kg bid)

Well tolerated with pronounced, dose responsive effects on arthritic index and hind paw thickness

www.sareum.co.uk

SDC-1802: Targeting Multiple Cancers

• Good efficacy in immunotherapy disease models vs many cancers

• New preclinical data presented at AACR-NCI-EORTC (Oct 2019)

• Anti-tumour effects seen in models of kidney, colorectal & skin cancers and B-cell lymphoma

• Evidence that SDC-1802 induces anti-cancer activity through a novel immunotherapeutic mechanism

• Positive results seen when dosed orally, as a monotherapy and with chemotherapy

• Current focus on initiation of short-term toxicity and dose-ranging studies

• Initial formulation studies complete; now optimising manufacturing route

8

SDC-1802 has no significant effect against pancreatic

tumour growth in immunodeficient mice

SDC-1802 gives significant reduction of pancreatic

tumour growth in immunocompetent mice

www.sareum.co.uk

TYK2/JAK1 and Covid-19

• Diseases such as Covid-19, SARS, MERS, influenza etc. can be fatal due to a “cytokine

storm” overreaction of the immune system

• Key cytokines elevated in Covid-19 ICU patients are reported to include:

• IL-2, IL-7, IL-10, G-CSF – all signal via JAK-family kinases

• Clinical trials of JAK-family inhibitors ruxolitinib, tofacitinib, baricitinib in Covid-19 patients are

in progress or planned

• Secondary bacterial infections induce IL-1β and GM-CSF

• GM-CSF reported to improve outcome in patients with pneumonia-associated ARDS

• IL-1β - GM-CSF pathway blocked by virally-induced IFNα and IFNγ

• TYK2/JAK1 inhibition blocks IFNα/γ signalling and thus restores GM-CSF levels

• GM-CSF signals via JAK2

• Suggests a TYK2/JAK1 inhibitor that does not inhibit JAK2 to be optimally beneficial

• Sareum’s SDC-1801/2 inhibit TYK2 and JAK1, but not JAK2

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Huang et al Lancet 2020; 395:497-506

Berg et al Eur Respir J 2017; 50:160193

Herold et al Am J Repir & Criti Care Med 2015; 189(5):609-11

IFN - Interferon; ARDS – Acute Respiratory Distress Syndrome

ICU – Intensive Care Unit; G-CSF – Granulocyte Colony Stimulating Factor

GM-CSF – Granular Macrophage Colony Stimulating Factor

www.sareum.co.uk 10

Licensing and Funding Opportunities

Tyrosine Kinase 2 / Janus Kinase 1 (TYK2/JAK1)

• Seeking co-development / licence partners for autoimmune and/or oncology applications

• Grant and other funding for Covid-19 applications

Checkpoint Kinase 1 (CHK1), FLT3+Aurora

• Demonstrates our ability to develop and commercialise clinical and preclinical candidates

• Potential for milestone and royalty payments

Funding

Psoriasis, RA, lupus, IBD, MS

T-ALL, ccRCC, immunotherapy

AML, ALL

Solid tumours

Anogenital

Prostate

Lung, colon,

Autoimmune

diseases

Cancer

Leukaemia

Monotherapy

Low dose gemcitabine

(LDG) combination

PARP inhibitor

combination

Immunotherapy combination

Lead

optimisation

Candidate

selection

TYK2/JAK1

FLT3+Aurora

Chk1

SDC-1801

Licensed to China-based

specialty pharma

SRA737

Clinical

Phase IITarget Preclinical

Clinical

Phase IPotential indications

SDC-1801