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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
5
7
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
– Rosemarie DeKruyff PhD
– Gordon Freeman PhD