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Triursus Therapeutics

Leading the Clinical Translationof Novel Targets for Immune Tolerance

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• Developing monoclonal antibodies against two key immune surface

receptors involved in immune regulation.

• Clinical strategy: Reduction of complications after hematopoieitic cell

transplantation.

• Seed stage company looking for:

– Additional seed investor to attain 8 month milestones.

– Eventual series A clinical trial funding.

• Developing humanized monoclonal antibodies against two different

surface receptors that when blocked aid in immune tolerance.

Overview

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• TR-2 is a surface receptor

• Recently, TR-2 has been shown to play a significant role in lung

mucosal immunity

• TR-2 is expressed in brain, lungs, pancreas, and intestines.

• TR-2 is expressed in the intestinal crypts, which is a primary site of

immune attack in GVHD

• Ligands of TR-2 mediate significant inflammatory signals on mucosal

surfaces in concert with TR-2 binding

• This suggests TR-2 plays a powerful and previously unappreciated

role in maintaining mucosal tolerance.

Showcasing Second Proprietary Target:

TR-2

0 20 40 60 800

50

100

Days elapsed

Pe

rce

nt s

urv

iva

l

RGMB Exp#2+#3

Tcon+BM

Tcon+BM+RGMB

BM only

Tcon+BM+PDL2

Anti-TR-2 Mab treatment enhances survival

p=0.0025

TR-2 binding site 1

TR-2 binding site 2

Separate experiments show no interference with anti-tumorimmunity.

Separate experiments show blockadeof human T cells transferred into miceprevents xenograft GVHD.

Four doses of mAb (200 ug/mouse)

Isotype TR-2 mAb site 1

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TR-2 mAb site 2

In vivo imaging of Donor T cells in

TR-2 antagonist mAb treated mice

0 5 10 15 20 250

1×107

2×107

3×107

Days

Ra

dia

nc

e (p

/se

c)

Tcon

Tcon+ anti-RGMB

Tcon + anti-PDL2

TR-2 site 1

TR-2 site 2

TR-2 mAb blockade of site 1 blocks in vivo proliferation whereas blockade of site 2enhances in vivo proliferation.

T cell proliferation (driver of GVHD):

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Protection of in islet transplantationAnti-TR-2 provides dramatic protection of transplants

Day 3

Day 5

Day 10

ShamPBS

Islet transpCtrl Isotype

Islet transpTR-2 Site 1

Day 12

Islet rejection

3 5 10 12

0

100

200

300

% r

espect to

basalin

e

Days post-transplantation

Balbcfemale

Analysis

-1 Day

Euthanasia

At 14 days

Post-transplant0

Anti-RGMb-Ab

i.p.; 200ug/mouse

Transplantation

Islet from

C57Bl/6 Luc+ mice

+3 Days +7 Days

TR-2 site 1 antagonist

ShamIslet + isotype

Islet + TR-2 site 1

Protection against gut colitis

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• Hematopoietic stem cell transplantation (HSCT) is the treatment of choice

for many hematologic malignancies and benign disorders

• Worldwide, ~25,000 allogeneic HSCT procedures in 2015

• Severe GVHD and respiratory failure represent huge hospital costs, often

$250,000-$1,000,000+ per patient and cases have a high mortality.

• Prophylactic treatment ($50K, with 50% penetration) represents a $750

million lead opportunity and rapid approval

Immune dysregulationin hematopoietic stem cell transplantation

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Pathway to Clinic: Phase I/II

Phase 1 Study • 9 patient dose finding study• Primary endpoint is safety at +28 days after last

administration of antibody.• Completion: 6 months

Phase 2/3 Study

• 150 – 250 patients, two arm double blinded study• Primary endpoint is acute GVHD incidence at 120

days. Secondary endpoints are incidence of non-relapse mortality, chronic GVHD and respiratory insufficiency by 180 days.

• Testing: reduction of GVHD from 40% to 20%.• Powered to show improvement in non-relapse

mortality as well.• Could include a pediatric population.• Completion: 24 months

Estimated cost $25,000 – 30,000 per patient.9

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Clinical, IP and Competition

Regulatory considerations

• Phase II clinical trials through Cancer Trial Network• Eligible for Orphan drug status, Fast Track,

Subpart H• Phase II study of 300 patients (anti-CCR5), estimate

80 patients total

Intellectual property

• PatentabilityStanford counsel indicates we have FTO andunique claims.

Competition • Post-transplant Cytoxan• Tregulatory cell therapy• Velcade• Anti-CCR5 MAb

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Seed Funding Goal (8 months)

Intellectualproperty

• Develop and declare 20 mAb candidates for each target, with 2-3 ideal lead candidates identified and humanized.

• Demonstrate efficacy of leads in vitro and in murine xenograft GVHD

Clinical Trial Preparedness

• Have clinical trial protocols drafted, preliminary contracting costs.

Fundraising • Apply for SBIR support (Jan 2017)• Consider licensing mAbs for immunohistochemistry

or flow cytometry (TR2).• Consider licensing agonistic antibodies for TR1 and

TR-2

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Seed Funding Commitment

Committed Funding

• $500,000 from Founders, Lake Pharma Partners, Corporate Lawyer as convertible loans.

SeekingAdditional Seed Stage Funding

• $250,000 from Angel Investor or Early Stage Venture

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Progress

TR1 • Have obtained lead candidate mAbs.

TR2 • Have obtained lead candidate humanized mAbs. Plan to test in human xenograft GVHD models in 1 month.

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• Two lead monoclonal antibodies targeting key pathways that set the

inflammatory immune thermostat

• Seeking seed funding to (1) generate and validate humanized monoclonal

antibodies and (2) prepare for definitive clinical trials.

• Clinical strategy: Orphan indication, fast to market, first to market

• Likely approval from Phase 2 randomized trial, requiring 250 patients

• Hard trial endpoints achieved quickly, within 6 months of transplantation.

Trial results achieved in 2-3 years.

Compelling Investment Rationale for Lead Indication

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Patients/Year (U.S.)

30,000 Organ transplantation, reduced graft

rejection and use of toxic drugs (Target 1 & 2)

13,000 Autologous HSCT, reduced mortality (Target 1)

30,000 Newly diagnosed type 1 diabetes,

prolong honeymoon (Target 2)

72,000 Inflammatory bowel diseases, gain

control of exacerbations (Target 2)

300,000+ Refractory type 2 diabetes, reduce

inflammatory inhibition of islets (Target 2)

400,000+ Virus-induced acute respiratory syndrome,

reduced morbidity and mortality (Target 1)

Additional Indications

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Contact Information

Management

• Science Advisory Board

– Everett Meyer MD PhD

evmeyer@stanford.edu

– Rosemarie DeKruyff PhD

– Gordon Freeman PhD