a dairy agtech start up · vagina through the production of organic acids such as lactic acid, h 2...

A Dairy AgTech Start Up

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NC Presentation from EJRobb 30 April 19

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Product Description PROPREG ™

Optimized Intravaginal Probiotic; “non-antibiotic” Manufactured under cGMP; CFR21 Part 111; ISO 9001 All Natural, microbes are GRAS, isolated from cattle non GMO Claim - Re-establish/augment vaginal microbiome Value –Healthy microbiome support post partum health/ reduced infections

“METRITIS” Benefits- Decrease use of antibiotics

Improved Start of LactationImproved Performance -Reproduction/Production related to health

Healthier Cows and Healthier Milk

Healthy Cow PROPREG™

Iowa PfG April_ 2019 HCC-CONFIDENTIAL

2014 1960

Average Life = 2.5Lactations1

4 YEARS / 2 PRODUCTIVE LIFE YEARS

Average Life =6Lactations1 Source: CanWestDHI

Dairy productivity hasimproved in the last 50years, but at the cost ofreduced animal lifespan

40% of dairy cow leave the herd due to poor reproduction

PROPREG™Healthy Cow

3Iowa PfG April_ 2019 HCC-CONFIDENTIAL

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Metritis pathogens in cattle are opportunistic environmental organisms that colonize the

reproductive tract, moving from the external environment and gain a

foothold in the vagina and uterus.

Uterine Infections occur in 30-40% of Dairy Cattle

Cost of Treat is approximately $500.00/case

Healthy Cow PROPREG™


• PROPREGTM

‣ Intravaginal probioticBased on research from the University of Alberta, CanadaLaboratory of Dr. Burim Ametaj, DVM, PhD

‣ Three natural endogenous lactic acid bacteria (Lactobacillus and Pediococcus) found in healthy cows, and low or absent in cows that subsequently required antibiotic treatments after calving

‣ Administered intravaginally (Applicator and Cartridge) ‣ Timing: Close to and after calving ‣ 2 weeks and 1 week Pre and 1 and 2 weeks Post ‣ Volume -10 mL contain over 4.5 Billion CFU of LABs

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What is PROPREG™

• University of Alberta Field Data‣ 5 years of Studies‣ +700 cows, multi-year, multi-location‣ Multiple Publications

PROPREG™


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DIRECTIONS FOR USE: PROPREG is for use only in healthy cattle by intravaginal administration. Place cartridge in applicator gun. Next, remove cap and secure using the bands provided and

secure the application tip to the flexible short tube cartridge and to the plastic application pipette.. Be sure to restrain cattle appropriately prior to and during administration. Assure the external

application area is clean. Clean and dry the applicator tip with an antiseptic wipe. Use lubrication if needed. Gently pass applicator tube tip past the vulva and insert approximately 6-9 inches (near

the junction with the cartridge). Administer 1 click (10 ml of gel). After administration, slowly remove applicator. Remove any course organic material and then clean and dry the external

surface of the applicator tube.

DOSAGE RATE: Each 300cc Cartridge contains a minimum of 28 doses. The cartridge is intended to use only with the dosing gun designed for this product. Each full pull of the trigger delivers 10cc of PROPREG gel. To ensure a full initial dose, depress trigger until the gel product appears at tip of applicator tube. Wipe off any excess gel. To store, clean the applicator tube. Replace the cap

onto the cartridge tip. See storage directions.

WHEN TO USE: Optimal establishment and maintenance of a healthy microflora to support reproductive health and productivity is established with PROPREG administration starting 4-6

weeks prior to calving until one-month post-partum. Consider grouping cows and apply weekly or every other week depending on herd size.

PROPREG administered twice to dry cows and springing heifers• 1st Administration: 2 weeks prior to expected calving date• 2nd Administration: 1 weeks before expected calving date

PROPREG administered twice post-partum 3rd Administration: 1 - week post-calving 4th Administration: 2 - weeks post-calving

PROPREG™

What is PROPREGTM :


How does it work

“ Under normal conditions the vaginal tract of a dairy cow is populated by a diversity of bacteria dominated mainly by lactic acid bacteria (LAB) (Otero et al., 2006; Rodriguez et al., 2011; Wang et al., 2013). Recently we showed that bacilli and LAB of the genera Enterococcus, Lactobacillus, and Pediococcus were present in the vaginal tracts of both healthy and infected cows (Wang et al., 2013). However, the infected cows a tremendous increase in the vaginal bacteria population that consisted mainly of Escherichia coli. (Wang et al., 2013).

An increasing body of evidence indicates that Lactobacillus strains suppress the growth of other endogenous bacteria in the vagina through the production of organic acids such as lactic acid, H2O2, and bacteriocins (Aroutcheva et al., 2001).

The production of organic acids maintains the vaginal pH at acidic values, thereby creating an inhospitable environment for the growth of most endogenous pathogenic bacteria (Reid, 2002).”

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PROPREGTM Scientific Foundation

PROPREGTM

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Data to Date

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PROPREGTM

An increasing body of evidence indicates that Lactobacillus strains suppress the growth of other endogenous bacteria in the vagina through the production of organic acids such as lactic acid, H2O2, and bacteriocins (Aroutcheva et al., 2001). The production of organic acids maintains the vaginal pH at acidic values, thereby creating an inhospitable environment for the growth of most endogenous pathogenic bacteria (Reid, 2002).

The mechanisms whereby lactobacilli function as antiinfective defenses are still not fully understood. As discussed, above, this may involve production of antimicrobial factors, and maintenance of a vaginal pH of ≤4.5. It could also be due to biosurfactants which alter the surrounding surface tension and reduce the ability of a wide range of pathogens to adhere [82, 83]. This might explain the relatively sparse coverage of epithelial cells noted in healthy women. In addition, lactobacilli have been shown to bind (coaggregate) some pathogens and this may be a meansto block their adhesion, kill them through production of antimicrobials, and prevent their spread to other areas of11292 by 60%; a 30% reduction in bacteriostatic effects was seen when catalase was introduced to degrade H2O2. Klebanoff et al. found that the toxicity of H2O2- producing lactobacilli was inhibited by the presence ofcatalase but lactobacilli that do not produce H2O2 were not affected. High concentration of H2O2-producing lactobacilli inhibits the growth of both G. vaginalis and Bacteroides bivius. Review Article Vaginal Microbiota and the Use of Probiotics

ProPregTM mechanism of action is like all other probiotics

Constellation of MechanismsCompetitive Exclusion, Barrier, Immune and Defense Mechanisms


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Healthy Cow Corp: The science inside PROPREGTM

• U Alberta 82 Cows• Tmt LAB Weeks -2, -1. +1,2,3,4 • CNT Same Schedule w Smilk

Abstract Conclusion-Overall, this is the first study demonstrating that intravaginal LAB administration lowers the incidence of PVD and enhances milk production in dairy cows. Further research is warranted to evaluate the effects of LAB on reproductive performancein a larger cohort of cows.

Abstract conclusion PLOSResults showed that intravaginal LAB lowered the incidence of metritis and total uterine infections. Intravaginal LAB also were associated with lower concentrations of systemic LBP, an overall tendency for lower SAA, and greater vaginal mucus sIgA. No differences were observed for serum concentrations of Hp, TNF, IL-1, IL-6 and total IgG among the treatment groups. Administration with LAB had no effect on the incidence rates of other transition cow diseases. Overall intravaginal LAB lowered uterine infections and improved local and systemic immune responses in the treated transition dairy cows.

• U Alberta 100 Cows• Tmt1 LAB Weeks -2, -1 and Sm w+1• Tmt2 LAB Weeks -2,-1 and +1• Tmt3 (Control) Smilk -2, -1,

PROPREGTM

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Healthy Cow Corp

Abstract conclusion JDSCows treated with LAB had smaller cross-sectional areas of gravid horn and uterinebody on d 14 postpartum. Cows in TRT2 resumed ovarian cyclicity earlier, as indicated by increased concentrations of serum progesterone. Cows in TRT1 had fewer days open than those in the CTR (110 vs. 150 d), whereas cows in TRT2 and CTR did not differ in days open. In addition, both TRT1 and TRT2 increased the concentrations of PGFM at calving week, and cows in TRT2 also had greater concentrations of PGE2 on d 14 and d 21 postpartum relative to CTR. Overall, cows treated intravaginally with LAB had smaller gravid horn and uterine body on d 14 postpartum than those in the CTR group.

• Paper 3-and 4 Same Ex Design as PLOS• U Alberta 100 Cows• Tmt1 LAB Weeks -2, -1 and Sm w+1• Tmt2 LAB Weeks -2,-1 and +1• Tmt3 (Control) Smilk -2, -1,

Abstract conclusion ASASBoth the TRT1 and the TRT2 groups had enhanced feed efficiency compared with the CTR group (P < 0.01). In conclusion, intravaginal infusion of lactic acid bacteria modulated concentrations of selected serum metabolites and milk components and increased milk efficiency of transition dairy cows.

: The science inside PROPREGTM

PROPREGTM

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PROPREGTM

• Farms A and C• Harvest milk under voluntary milking system (VMS)• Collection occurs around 24 h periods• Breed = Holstein

• Farm B • Organic farm• Harvest milk under voluntary milking system (VMS)• Collection occurs 24 h periods• Breed = Jersey

• Farm D• Harvest milk under parlour dairy system • Collection occurs 3 times a day approximately at 0400,

1200, and 1800 h• Breed = Holstein


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Incidence Uterine

Infections

Health

Postpartum health Supports Healing Health1 2 3 Reduces Abx use4

PROPREGTM

TRT 11 TRT 22 TRT 33 P-value

Farm A 39.47% (30/76)a

31.58% (24/76) a

28.95% (22/76) b 0.14

Farm B(organic Jersey)

40.00%(12/30) a

40.00% (12/30) a

20.00% (6/30) b 0.03

Farm C 42.42% (28/66) a

33.33% (22/66) a

24.24% (16/66) b 0.05

Farm D 25.00% (16/64) a

46.88% (30/63) b

28.13% (18/64) a 0.05

Overall 37.1% (43/116) a

36.1% (31/116) a

26.7% (31/116) b 0.04

PROPREGTM uses 3 different probiotics strains of natural native Lactobacillus Bacteria (LAB) to help optimize, repopulate and maintain a healthy bovine vaginal microbiome pre and post calving.

Note: Denominator is cows with uterine infection not cows at risk


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Disinfectants Hormones Antibiotics ProPregTM

ActiveCompound

Iodine, chlorohexidine, cresol Prostaglandins, estrogen, oxytocin, ergonovine

Penicillin, tetracycline, aminoglycosides,

nitrofurazone, sulfonamidesLAB Consortia

Regulatory No indication Drugs some off label Drugs some off label In discussion

Application Infusion flush Injection Infusion flush & Injection

Intra vaginal Infusion

MoA Chemical Uterine contraction Microbial Bacteriocins, pH, immune, H2O2

Prevention No No Illegal Use YesIrritation Yes Injection Site Injection Site No

Contribute to Microbial Resistance

Exerts Pressure No Yes No

Residues & Milk Discard

Yes Yes/No Yes/No No

“Green” No No No Yes

What will PROPREG Displace?PROPREGTM


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PROPREGTM is a viable alternative to antibiotics in Ag


What will PROPREG Displace?PROPREGTM

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PROPREGTM

How ProPregTM Target Product Profile


• Composition– Consortia of 3 bacterial isolates for a

total of 1x109 CFU/dose– Known yield & COG

• Ready-to-Use tube with Cap– “Dried” & suspended in anhydrous gel

for retention– Sanitary Applicator -minimizes cross

contamination ( to address # per carton)

• Validated Cleaning Procedure

– Stability: 2 years shelf-life*(Pending)

– Storage: Room Temperature• 30 (or 28) doses per tube (300cc)

– Optimal Dose: 1 x 109

CFU/dose – Dose Volume: 10 mL /

dose• Sanitation to address inclusion or in directions

• Carton of 6 cartridges 180 doses (5.2 lbs.) • 6 cartons per case (32 lbs.) About 970 doses• Stability ongoing

Regimen:• 1xDose @ Dry-of 2-3 wk• 1xDose @ Close-up, 1-2 4wk• 1xDose @ +1 week• 1xDose @ +2 week

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PROPREGTM

How ProPregTM Target Product Profile


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Sanitation

Gloves for applicator Cows vulva must be clean and dry Lubrication may be used Cleaning procedure for applicator between uses.

Both have spectrum for repro pathogens Storage-Remove Applicator and replace

Cartridge Cap

PROPREGTM

How PROPREGTM is used: Sanitation


Regulatory Strategy

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PROPREGTM


Regulatory Pathway

Article of Commerce

Support normal vaginal microbiome

USDA CVB

Prevent / Treat uterine infections

FDA CVM

Function: Productivity, Fertility

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PROPREGTM

Market Value

• Market (Values are estimates for discussion)

– EU has 25M Dairy Cows– ROW has 120M Dairy Cows

• Late 2019/early 2020 Market Ready New Product

– Quality CMO in Place cGMP, 21 CFR Part 11 Compliant (Safe Food and Drug) ISO 9001– Partner must align with the claim ”establish and maintain a health vaginal microbiome in

cattle” – Patents filed on formulation, tooling, engraftment. Additional filings in plan

US/Canada can provide $25M (USD) Profit opportunity with good margins and turn over to Trade Partners


Addressable market:a) 30-40% of herds in CAD, USA, EUb) Top 50% percentile in herd SCCc) Progressive dairy producers (robotics, pro-health, welfare)

10,000,000 Million Cows 4 dose Regimen40% Addressable10% 25% 50% 65% Penetration

400,000 1,000,000 2,000,000 2,600,000 # cows Treated20.20$ 20.20$ 20.20$ 20.20$ 4 Dose Regime at Farm Gate

8,080,000$ 20,200,000$ 40,400,000$ 52,520,000$ Farm Gate Value20.20$ 20.20$ 20.20$ 20.20$ Channel Patner (60% Margin) 12.00$ 12.00$ 12.00$ 12.00$ Transfer $ From ProPreg to Partn

4,800,000$ 12,000,000$ 24,000,000$ 31,200,000$ ProPreg Capture

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PROPREGTM

PROPREG Economics

From Zoetis: Metritis A Foul Disease with Financial Costs

Additional costs:Include:• Lost Genetic Merit• Cost of Days Open• Labor • Disposal

Adds $150.00/case

Total cost $500/case


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PROPREGTM

PROPREG Economics

ProPreg ROI Base CaseMetritis

Calvings Per Year 115 345 575 920 1150Cows Per Herd 100 300 500 800 1000ProPreg /Per Dose $5 $5 $5 $5 $5# of Doses 4 4 4 4 4Cost of Treatment / cow $20 $20 $20 $20 $20Total Farm cost of Treatment $2,300 $6,900 $11,500 $18,400 $23,000

Prevalence of Metritis 30% 30% 30% 30% 30%Total affected cows 34.5 103.5 172.5 276 345Avg Cost per Case $ 500 $ 500 $ 500 $ 500 $ 500 Cost of Metritis $ 17,250 $ 51,750 $ 86,250 $ 138,000 $ 172,500

ProPreg Preventive Fraction 40%Preventive Fraction $ 6,900 $ 20,700 $ 34,500 $ 55,200 $ 69,000 (Metrits cost x PF (40%)

ROI Ratio (ProPreg Cost/$ Saved) 3.00 3.00 3.00 3.00 3.00

Sensitivity• @ 20% Metritis Incidence and 40 % Reduction ROI is 2.0X• @ 30% Metritis Incidence and 25 % Reduction ROI is 1.9X• @ 20% Metritis Incidence and 20 % Reduction ROI is 1.0 (Break Even)• @ $354 Cost Estimate in Base Case ROI is 2.12 X • Other value drives as well


• Approximately $500k Investment to Date by Alberta Dairy Framers additional $400k for Gov Grants and $400k Founder Equity

• Healthy Cow Corp Seeks Investment to Complete Development and Initiate Commercialization.

– Complete Development US and Canada• Seek $1M to Complete Studies (June-Dec 2019)

– 1000 Cow ‘Conditions of Use’ with Final Formulating– Engraftment Bacterial: Kinetics– Repro Safety for Canada– Canadian Registration Costs

• Seek addition $3M to Commercialize – Late 2019 early 2020– 6-7 Technical Reps/Sales Support/Marketing/Logistics

• ROW Growth funded by Sales success late 2020

• Healthy Cow Est Market Cap Today- approx. 9 M$• Seek Investment: Private Placement (shares) or Convertible Notes (warrants)

Iowa PfG April_ 2019 HCC-CONFIDENTIAL 23

PROPREGTM

PROPREG Economics

Thank you

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PROPREG™

• Translation from University Research to the Farm

• Greater than 700 cows tested

• Stable-RTU Formulation

• CMO cGMP w/ Known Yield and COGs

• “Green” and Sustainable

• Application Devices Optimized

• Safety (Local Tolerance)

• Patents Filed

• Regulatory Alignment Achieved

• Positive ROI for Partners and Producers

• Solid Business Case

Partner with Healthy CowPROPREGTM

• Partnering Opportunities– Exclusive Distribution Licenses

• Territory/Global– Investment Options– Acquire

• HCC expansion to Equine and Swine in addition to other specialty probiotic lines

– Optimization (Enhanced Engraftment) to decrease admin freq)

– Optimize CFU Load• HCC has other food animal POC programs

– ProMunity Endotoxin Oral Vaccine– Mastitis Diagnostics

• Contacts: 269 993 8045• Ed, Louis and [email protected]@healthycow.ca, [email protected]

mailto:[email protected]

mailto:[email protected]

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• Right Product Right Time

• Investor Ready

• Research Driven

• Experienced Leadership Team

• Win-Win for the Cow, the Producer, the Dairy, the Creamery, the Consumer and the Environment

• Manufacturing De risked, favorable COGs

• Clear Pathway to Market

• Will reduce Abx Use

• Microbiome Product

• Scale Neutral all: Farms Benefit


PROPREGTM

Thank You

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Our team: Key ManagementRichard Strafehl, CEO is a serial entrepreneur with expertise in technology commercialization, sales, marketing and corporate strategy. In biotech, he brings 12 years of experience as co-founder of Safeguard Biosystems Inc. a molecular diagnostic company (human, animal health and food safety). Prior to his shift into biotech, he spent 20 years with companies such as Xerox, AT&T, NCR, Interac in bringing new large data and enterprise systems solutions to the banking and telecommunications industry. He has been part of several start-ups, a number of which have had successful exits through IPO or sale.

Dr. Edward Robb, DVM. MS. DACVN, CVO brings 35 years of animal health pharmaceutical and executive experience. He has worked in senior executive positions responsible for research, development and regulatory affairs for CEVA Animal Health LLC, Boehringer Ingelheim Vetmedica, Inc. Pfizer Animal Health (no Zoetis) and American Cyanamid Company. Prior to his executive career, he worked as a practicing Dairy Veterinarian in New York State and lecturer in Veterinary Epidemiology and Clinical Nutrition at the University of Pennsylvania School of Veterinary Medicine.

Louis Hui, COO, brings 8 years of biotech and animal health pharmaceutical and executive experience. Prior to becoming an entrepreneur, he worked as University Tech Transfer Manager at Simon Fraser University, NovaNAIT Centre for Applied Research.He was also Business Analyst at Resverlogix Corp. and venture capital analyst for AVAC Group, an ag-biotech venture fund. He received his Masters of Biomedical Technology at the University of Calgary and BSc in Biology and the University of Western Ontario.

Barbara Merlo, VP Finance & Corporate Services, has 20 years of experience in sales, marketing, finance, purchasing and project management in early stage businesses. She was a co-founder of Safeguard Biosystems, a medical diagnostics company. Prior, she had her own consulting practice in large organizational events management including Young Presidents Organization and Corporate Marketing Director for Expo ’86. After graduating from Simon Fraser University (B. Comm), she was a sales executive for XeroxCorporation.

Marcelo Garza, Latin America Business Analyst, is an MBA candidate at Rotman School of Management, University of Toronto. He received a degree in Food Science from Penn State University, in food microbiology, food chemistry, food analysis and processes. He has 6+ years of experience in the food industry at Sigma Alimentos, a multinational food company that has presence in 17 countries in Mexico, USA, South America and Europe, where he worked in Sales, Marketing, R&D, Product Development, and Packaging Innovation. Marcelo is developing the Company’s product launch in Latin and South America.

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Our team: Key AdvisorsDon West, Legal Counsel, is a partner at Aird & Berlis, Toronto. Don is a member of the firm’s Corporate/Commercial, Mergers & Acquisitions/Private Equity, Technology, Licensing and Telecommunications Groups. Practising in the areas of business law, mergers and acquisitions, corporate finance, and technology, he has had extensive experience acting on business purchases and sales, private equity and venture capital transactions, strategic alliances, technology transactions, corporate reorganizations, governance issues, international transactions and advising on various other commercial arrangements.

Dr. Burim Ametaj, Scientific Advisor, is a Professor of Animal Physiology and Nutritional Immunology at the Department of Agricultural, Food, and Nutritional Science, University of Alberta, Canada. Dr. Ametaj does research on Dairy Cow Health including developing new technologies for prevention of periparturient diseases such as an oral vaccine, an intravaginal probiotic cocktail, a grain processing technology, and identification of monitorng biomarkers for six diseases. In addition Dr. Ametaj is involved in studying the etiopathology of prion diseases and developing a preventive treatment against brain neurodegerative diseases.

Muna Abu-Shaar, Patent Attorney, is an intellectual property attorney with over fifteen years of experience in patent counseling for biotechnology and pharmaceutical industry clients ranging from startups to Fortune 500 companies. Muna received a J.D. from Fordham Law School (cum laude), a Ph.D. (with distinction) in Cellular, Molecular & Biophysical Studies from Columbia University, and a B.A. in Natural Sciences from the University of Cambridge. She was recognized as a Super Lawyers "Rising Star" in New Yorkin 2011 and 2013. Prior to founding Biospark Intellectual Property Law, Muna was a partner in the intellectual property group of a large international law firm.

Jeff Nonay, Dairy Producer Advisor, is the owner and proprietor of Lakeside Dairy in Alberta (http://lakesidedairy.com). He created the “Grow Naturally” logo to reflect his philosophy of using natural processes to change how and what they produce. He continues to lead the industry in the implementation of new technologies and sustainability practices in producing the best quality dairy and food products.

Maurice Moss, Financial Advisor, is a partner at HSM LLP, and as a Chartered Professional Accountant. Maurice provides accounting, tax and related services to small and medium size family businesses. Maurice hold an honors Bachelor of Commerce degree from University College Dublin, Ireland. His initial experience was obtained with one of the big 4 in Dublin, Ireland. His first C.A designation was obtained in Ireland. He subsequently gained his Canadian C.P.A designation following his immigration to Canada with his family.

http://lakesidedairy.com/

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THANK YOU

a dairy agtech start up · vagina through the production of organic acids such as lactic acid, h 2...

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