mesentech is a regenerative medicine company developing ......c3 (c4, c5, c6) – pct/ib2016/053482...

Jonathan Polak, CEO(774) 234-8018

[email protected]://mesentech.com

Regenerative medicine for reversing bone loss

Mesentech is a Regenerative Medicine company developing drugs that build bone. These drugs can be used locally (implants) or systemically to reverse diseases like osteoporosis

Founded by Dr Robert Young – 30 year veteran of Merck where he led discovery pharmaceuticals Singulair® and Vioxx® with sales >$80 billion.

October 2018



Severe osteoporosis patients will risk increased cancer risk for treatment

Despite black-box warning for increasing cancer risk Forteo (Eli Lilly) sells $1.7B/yr. Tymlos approved early 2018 already doing $100M/yr

Normal bone Osteoporotic bone



● OI is caused by genetic defects that affect the body's ability to make bone.● Prevalence 7/100,000 ~ 20k in USA, 30k in EU● Pediatric advantage (no other options available)

Osteogenesis imperfecta (brittle bone disease)



● Rare disease affecting males (~ 4/100,000). ● Steroids are first line but cause severe osteoporosis as a side-effect● Similar indication to steroid induced osteoporosis in rheumatoid arthritis

Duchenne muscular dystrophy



Orphan diseases make great exists

● Canadian biotech developing treatment for rare bone disorder (fibrodysplasia ossificans progressiva 1 per 2 million)

● IPO (Aug 2017) mkt cap @ $475M. Nov 2018 Mkt Cap = $493M

● IPO based on single phase 2 study (NCT02190747) in 40 patients

Clementia (NASDAQ:CMTA)Enobia (acquired by Alexion)● Canadian biotech developing

treatment for rare bone disorder (Hypophosphatasia 1 per 300,000 )

● Acquired (Feb 2012) by Alexion for $1B ($670M + $410M). 2018 sales > $500M

● Acquisition based on single phase 2 study (NCT00952484) in 13 patients (open-label)



How C3 works

Conjugate carries drug in an inactive state until it binds to bone

When conjugate bond breaks, active drug is released into the bone

Drug binds to stem cell stimulating osteoblast maturation



Proof of Concept in ovariectomy rats

Active: Dosed once a week 5mg/kg

*Using C1 (an earlier version of the C3 conjugate)

Control Active*



US $3.4 billion market Growth 6% in USA; 20% in China

● 500,000 procedures/year in US. ● Short clinical trial: single dose,

topical application● High-margin applications in

sinus-augmentation and spinal-fusion to replace Infuse®

Dental implants - a large and growing market



Disc - no C3(control)

Disc - with C3

Micrograph showing augmented vertical bone growth along a titanium screw with the use of Mesentech's treatment resulting in osseointegration.

Proof of concept: Dental implant & spinal fusion

ActiveControl



Financing

$1.5M SAFE

∗ Preferred shares upon conversion∗ Capped: you pay the lower of 0.75/share (8.7M excluding options) or

20% below next round∗ 8% interest accrues until conversion∗ 2X liquidity preference ∗ Right to convert to common anytime



1.Diseases like Osteoporosis...but we will first target orphan diseases such as pediatric brittle bone disease (osteogenesis imperfecta) and comorbid osteoporosis arising from the treatment of Duchenne’s muscular dystrophy.

2. Synthetic bone graft material...but we will first target dental implants -- shortening procedures to 1 week from 12 weeks (10x faster osseointegration). For more complex indications this is a drop-in replacement for BMP (Infuse™) with sales ~$800M

Markets we can address



Supporting slides



Key Personnel

Robert YoungFounder & President

Jon PolakCEO

Michael UnderhillCo-founder & CSO

Peter SavasExecutive Chairman

Advisors: Michael Glogauer, Marc Grynpas, Ian Mcbeath (Founding CEO)Founders: Pieter Cullis, Fabio Rossi



Investment thesis

Mesentech has developed a bone-targeting drug-conjugate that is order of magnitude cheaper than antibody based conjugates. ● Dual small-molecule targeting moiety and small-molecule payload allow Mesentech to compete in

indications where the entire procedure is

Multiple APIs with separate patents allow for independent licensing of separate indications

Huge exit possible while providing numerous value-inflection points● Several orphan indications for speed to market and broader, non-orphan indications to make >$1B

potential

High unmet need due to technical barriers and aging demographic ● Bone is tough to drug. Systemic products require high doses and fail due to side effects/toxicity.



Development plan

OI

graft

OVX

Pre-clinical1-2 years

Toxicology1 year

Human efficacy2-3 years

PoC2017

PoC06.2018

PoC06.2019

IND IPOValidation02.2019

• orphan (OI)• oral/maxilofacial• orthopedic

OI

graft

osteoporosis



Mesentech (C3)

PTH (Forteo)

BMP (Infuse)

sclerostin-Mab (Mereo)

Clinical Indication topical and systemic indications

Osteoporosis topical only (e.g. spinal fusion)

OI (Mereo) & Osteoporosis (UCB/Amgen)

Modality small molecule - targeted to bone

biologic - systemic biologic - topical biologic (antibody) - systemic

Long term use Yes No. Max 2 yr duration.

No. Single Use Unknown)

Use in children Yes FDA denied pediatric clinical trial

Systemic Indication Yes Yes No Yes

Local Indications Yes No Yes No

Sales pre-market 1.75B (2017) $480M (2015) pre-market

Key Limitations triples cancer risk - ectopic bone- expensive biologic

Cardiovascular events found in P3 trial

Competitors – Bone Anabolic Products



C3 drug-conjugate

C3 consists of of two parts: 1. alendronate + linker (targeting moiety) 2. EP4a (drug moiety)



Case study

Mrs X. is a 78-year-old woman with a past medical history of hypertension, mild cognitive impairment, and osteoporosis treated with a bisphosphonate. She trips on a carpet at home and sustains a femoral neck fracture requiring open reduction with internal fixation. Postoperatively she develops delirium and is diagnosed with a catheter-associated urinary tract infection. She does not return to her baseline level of functioning and a decision is made to discharge her to a long-term care facility.



Current patent suite (3 series) with R. Young et al as inventors

● C1 - PCT/CA2011/000633; WO 2011/147034 A1 (Priority May 28, 2010)

● C3 (C4, C5, C6) – PCT/IB2016/053482 (Priority date June 15, 2015)

● C7, C8 - US Patent 9650414 B1, Granted May 16, 2017. (Priority date May 14, 2015)

Several more patents in preparation

Strong IP Linkers and conjugates are novel and patentable



C3 reverses osteoporosis in ovariectomy rats

Active

● Rats with ovaries excised show rapid bone loss

Ovariectomy rats

● C3 reversed bone loss(Pre-clinical efficacy)



Dosing drug moieties separately has no effect

C3 reverses osteoporosis in ovariectomy rats

C3 restores bone to original levels

Rat with ovaries excised shows rapid bone loss

Original unmodified rat

Alendronate amide EP4a + alendronate amide

Original TreatedUntreated

Control treatments



OVX Proof of Concept in ovariectomy rats

SV - shamOV - ovariectomyCL - C1 low doseCH - C1 high doseEA - EP4 + alendronate PG - prostaglandin

SV OV CL CH EA PG



Histomorphometric analysis of tissue-level bone turnover in the proximal tibial metaphysis

BV/TV trabecular bone volume, MS/BS mineralizing surface, MAR mineral apposition rate, BFR/BV bone formation rate normalized over bone volume, BFR/BS bone formation rate (surface referent), OV/BV percent osteoid volume, OS/BS percent osteoid surface, Oc.S/BS percent osteoclast surface, N.Oc/BS osteoclast density. *p



1. Bone esterase cleavable. Rates can be tuned by modification of the ester substitution. Optimal t1/2 170 h (once a week)*.

2. Bone protease cleavable of tuned peptide followed by rapid self immolation (rate controlled by peptide cleavage)**.

3. pH cleavable (spontaneous) either pH 7 or 5. Conjugates stable and T1/2 release is long (once a week).

* Chen, G, Arns, S. and Young RN, Bioconj. Chem. (2015) 11, 536-54** Xie, H, Chen, G and Young, RN, J. Med. Chem, (2017) 60, 7012-28.

Proprietary linker technologies

mesentech is a regenerative medicine company developing ......c3 (c4, c5, c6) – pct/ib2016/053482...

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