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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
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Jonathan Polak, CEO(774) 234-8018
[email protected]://mesentech.com
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
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Jonathan Polak, CEO(774) 234-8018
[email protected]://mesentech.com
● 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)
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Jonathan Polak, CEO(774) 234-8018
[email protected]://mesentech.com
● 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
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Jonathan Polak, CEO(774) 234-8018
[email protected]://mesentech.com
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)
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Jonathan Polak, CEO(774) 234-8018
[email protected]://mesentech.com
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
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Jonathan Polak, CEO(774) 234-8018
[email protected]://mesentech.com
Proof of Concept in ovariectomy rats
Active: Dosed once a week 5mg/kg
*Using C1 (an earlier version of the C3 conjugate)
Control Active*
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Jonathan Polak, CEO(774) 234-8018
[email protected]://mesentech.com
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
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Jonathan Polak, CEO(774) 234-8018
[email protected]://mesentech.com
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
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Jonathan Polak, CEO(774) 234-8018
[email protected]://mesentech.com
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
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Jonathan Polak, CEO(774) 234-8018
[email protected]://mesentech.com
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
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Jonathan Polak, CEO(774) 234-8018
[email protected]://mesentech.com
Supporting slides
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Jonathan Polak, CEO(774) 234-8018
[email protected]://mesentech.com
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
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Jonathan Polak, CEO(774) 234-8018
[email protected]://mesentech.com
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.
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Jonathan Polak, CEO(774) 234-8018
[email protected]://mesentech.com
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
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Jonathan Polak, CEO(774) 234-8018
[email protected]://mesentech.com
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
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Jonathan Polak, CEO(774) 234-8018
[email protected]://mesentech.com
C3 drug-conjugate
C3 consists of of two parts: 1. alendronate + linker (targeting moiety) 2. EP4a (drug moiety)
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Jonathan Polak, CEO(774) 234-8018
[email protected]://mesentech.com
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.
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Jonathan Polak, CEO(774) 234-8018
[email protected]://mesentech.com
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
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Jonathan Polak, CEO(774) 234-8018
[email protected]://mesentech.com
C3 reverses osteoporosis in ovariectomy rats
Active
● Rats with ovaries excised show rapid bone loss
Ovariectomy rats
● C3 reversed bone loss(Pre-clinical efficacy)
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Jonathan Polak, CEO(774) 234-8018
[email protected]://mesentech.com
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
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Jonathan Polak, CEO(774) 234-8018
[email protected]://mesentech.com
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
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Jonathan Polak, CEO(774) 234-8018
[email protected]://mesentech.com
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
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Jonathan Polak, CEO(774) 234-8018
[email protected]://mesentech.com
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