adocia corporate presentation - march 2017
TRANSCRIPT
CORPORATE PRESENTATIONMARCH 2017
Disclaimer This corporate presentation (the “Presentation”) has been prepared by ADOCIA (the “Company”) and is provided for information purposes only. It is not for promotional use. References herein to the Presentation shall mean and include this document, any oral presentation accompanying this document provided by the Company, any question and answer session following that oral presentation and any further information that may be made available in connection with the subject matter contained herein.The information and opinions contained in this document speak only as of the date of the Presentation and may be subject to significant changes. The Company does not undertake any obligation to update the information or opinions contained herein in light of any new information or future developments.The information contained in the Presentation has not been independently verified. No representation, warranty or undertaking, express or implied, is made as to the accuracy, completeness or appropriateness of the information and opinions contained in this document. The Company, its subsidiaries, its advisors and representatives accept no responsibility for and shall not be held liable for any loss or damage that may arise from the use of the Presentation or the information or opinions contained herein.The Presentation contains information on the Company’s markets and competitive position, and more specifically, on the size of its markets. This information has been drawn from various sources or from the Company’s own estimates. Investors should not base their investment decision on this information.The Presentation does not purport to contain comprehensive or complete information about the Company and is qualified in its entirety by the business, financial and other information that the Company is required to publish in accordance with the rules, regulations and practices applicable to companies listed on Euronext Paris. The Company’s annual reference document for the year ended December 31, 2015 filed with the French Autorité des marchés financiers (the “Financial Markets Authority”) on April 8, 2016 and available in an English convenience translation on the Company’s website, in particular its Risk Factors section found in Section 4, as well as any other of its periodic reports should be carefully reviewed. Information and other data appearing in such publications, and certain figures and numbers appearing in the Presentation have been rounded. Consequently, the total amounts and percentages appearing in tables and elsewhere may not necessarily equal the sum of the individually rounded figures, amounts or percentages.The Presentation contains certain forward-looking statements. These statements are not guarantees of the Company's future performance. These forward-looking statements relate to the Company's future prospects, developments and marketing strategy and are based on analyses of earnings forecasts and estimates of amounts not yet determinable. Forward-looking statements are subject to a variety of risks and uncertainties as they relate to future events and are dependent on circumstances that may or may not materialize in the future. Factors that may cause actual results to differ materially from those contained in any forward-looking statements include the uncertainties relating to research and development, results of clinical trials, success of the Company’s collaboration agreements and decisions by regulatory authorities regarding approval of the Company’s products, as well as those discussed or identified in the public filings made by the Company with the Financial Markets Authority. Forward-looking statements cannot, under any circumstance, be construed as a guarantee of the Company's future performance and the Company’s actual financial position, results and cash flow, as well as the trends in the sector in which the Company operates, may differ materially from those proposed or reflected in the forward-looking statements contained in the Presentation. Even if the Company’s financial position, results, cash-flows and developments in the sector in which the Company operates were to conform to the forward-looking statements contained in the Presentation, such results or developments cannot be construed as a reliable indication of the Company's future results or developments. The Company does not undertake any obligation to update or to confirm projections or estimates made by analysts or to make public any correction to any prospective information in order to reflect an event or circumstance that may occur after the date of the Presentation.The Presentation does not constitute an offer to sell or subscribe or a solicitation to purchase or subscribe for securities in France, the United States or any other jurisdiction. Securities may not be offered or sold in the United States absent registration under the US Securities Act of 1933, as amended, or an exemption from registration thereunder. No public offering of securities will be conducted in France or abroad prior to the delivery by the Financial Markets Authority of a visa on a prospectus that complies with the provisions of Directive 2003/71/CE as amended. No public offering of securities is contemplated in France or any jurisdiction outside France.The distribution of the Presentation may be restricted by law and persons into whose possession this document comes should inform themselves about, and observe, any such restrictions. All persons accessing the Presentation are deemed to agree to all the limitations and restrictions set out above.
March 2017 2
INTRO
Management Team
March 2017 3
ADOCIA
Gérard SoulaPhD, MBA
Olivier Soula PhD, MBA
Valérie Danaguezian Rémi SoulaPhD, MBA
Steve Daly
President & CEOCo-founder
Deputy General Manager, R&D DirectorCo-founder
Chief Financial Officer Director of BD & IPCo-founder
US General Manager
ADOCIA in summary
March 2017 4
ADOCIA
Specialist in protein-based diabetes treatments, providing innovative therapeutic options
1
Business model based on already-approved proteins, enhanced with BioChaperone®2
Phase 3 – ready ultra-rapid insulin BioChaperone Lispro 3
Strong pipeline with new clinical launches expected in 20174
Proven management team with successful track-record5
Solid cash position6
Corporate Fact Sheet
Focused on Diabetes treatment using already-approved therapeutic hormones to address core-defects:
BioChaperone prandial insulins: BC Lispro (Phase 2) & HinsBet (Phase 2) BioChaperone Insulins Combo (Phase 2) New programs: BC Glucagon, BG Glargine GLP-1 combos, BC Lispro combos
(preclinical) Founded in 2005 by Gérard, Olivier & Rémi Soula
Listed on Euronext (ADOC) - Market Cap €142M*; Share Price: €20.70* (from €15.90 @ IPO Feb 2012)
Cash position end of December 2016 :€58M (€85M raised to date) Experienced executive team; 125 employees including 46 PhDs, MDs, PharmDs
BioChaperone® unlocks the potential of hormones and their combinations Expanding treatment options by solving difficult formulations challenges 30 patent families ; validated in 15 human clinical trials to date
March 2017 5
ADOCIA
* As of Feb 10, 2017
Our mission is dedicated to the treatment of diabetes
March 2017 6
ADOCIA
Provide people with more physiologic treatments of diabetes
in a simple and affordable way
to help them avoid severe consequences of their disease
Broad portfolio addresses the diverse medical needs of diabetes patient populations
March 2017 7
ADOCIA
Clinical programs Preclinical programs
BC Lispro U100BC Lispro U200BC Gla Lispro
HinsBet U100HinsBet U500
BC Glucagon
BC Lis Pram
BC Gla LiraBC Gla Dula
In vitro
PC Phase I/II Phase III
BC Lis Exe
In vitro PC Phase I/II
(BC Combo)
Supported by a Top-Tier Medical Advisory Board
There remains a real medical need in diabetes
March 2017 8
DIABETES
79%3 live with severe
complications
Despite 100 years of medical treatment, long-term consequences of diabetes remain a major issue
People with T1D in particular, are still confined to insulin treatment ‘alone’
There is a need to address the underlying complexity of diabetes
With more granularity In a simple way to ensure patient
engagement
415M1
people with diabetes in
2015
26M2 on insulin
1 International Diabetes Federation, Diabetes Atlas 2015; 2 Estimate based on 25% of diabetes patients having access to care, of which ~25% use insulin, as per Novo Nordisk, Full Year 2014 Investor presentation ; 3 Hazel-Fernandez & al; Am J Manag Care. 2015. Patients with a Diabetes Complications Score Index of 1 or more, in a sample of 333,576 Medicare advantage plan members diagnosed with diabetes.
Sustainability of the healthcare systems raises a major cost-effectiveness challenge
March 2017 9
DIABETES
1 American Diabetes Association, “Economic Costs of Diabetes in the US in 2012”, 2013.
Need for sustainability of healthcare system, especially in pandemic disease like diabetes:
Pressure on drug pricing Advent of biosimilar drugs Emergence of value-based models
Volume will drive growth in the diabetes market Currently, millions of patients do not yet benefit from
innovation due to cost hurdles
$29B1 for
antidiabetic drugs and supplies (12% of
total, 2012, US)
$245B1
Diabetes -related costs (2012, US)
3 pillars support the future of diabetes treatment
March 2017 10
DIABETES
Affordability
Patient engagement
More physiologicapproaches Ultra-rapid insulin action
Combo of synergistic hormones
Synchronized hormonal actions
Enable simple combinations Use of approved
hormones vs. NCE Shorter clinical
development
BioChaperone® unlocks the potential of hormones and their combinations in a cost-effective way
March 2017 11
ADOCIA
[BioChaperone® Hormone]Complex
(library of molecules)
BioChaperone®
Accelerat
ed absorptio
n
Improved solubility
Improved stability
Hormones(insulin, GLP-1 RA, amylin, glucagon)
Simple formulation approach Leverage existing
manufacturing capabilities
Easy implementation
32 patent families On BC molecules and
formulations 1st expiry date 2033Potential
benefits
Formulation enables affordable innovation
With BioChaperone®, Adocia develops innovative and cost-effective new treatments for diabetes
Innovative formulation allows opportunity to improve and combine approved hormones with established track-records
Enhance performance of individual hormones Enable combination of “un-combinable” hormones
This approach to innovation has the following advantages: Reduced level of risk Shorter clinical development Lower investment levels (clinical and manufacturing)
March 2017 12
ADOCIA
Lean business model provides innovative treatments in a competitive landscape
Adocia licensing business model targets diabetes players
Early licensing opportunities allow for faster return on investment Adocia is evolving towards a more sustainable, higher-value licensing business
model Shift from « proof-of-concept » to late-stage, Phase 3 ready projects Developing different risk-reward sharing strategies
March 2017 13
ADOCIA
BIOCHAPERONE INSULIN CLINICAL PROGRAMS
March 2017 14
A more physiologic short-acting insulin for better outcomes
March 2017 15
BC LISPRO
More time-in-range (less hypoglycemia and less hyperglycemia)
More flexible dosing options at mealtime
Potential benefitsBioChaperone® Lispro U100
BioChaperone® Lispro U200
$7BPrandial insulin market (2015)1
1 Source: Adocia estimates based on major companies annual reports, 2015
Faster BC Lispro improves glycemic control
March 2017 16
BC LISPRO
Liquid meal+ Insulin s.c.
AUC0-2h:
Trial in 38 subjects with type 1 diabetes (NCT#02213146) ; *CI-95% for LSM ratioThese results were the subject of an oral presentation by Dr Tim Heise (Profil Neuss) during the 76th Scientific Sessions of the American Diabetes Association (June 2016).
-61%*
Accelerated absorption and better post-prandial control for BC Lispro U100 vs. Humalog observed across T1D & T2D patients & devices
BC Lispro U200 is the most advanced ultra-rapid concentrated insulin in development. Potential for co-filing with U100
BC Lispro has a complete dossier to enter into phase 3
Adocia is actively looking a potential partner
Post-meal glycaemia in T1D
For more detailed results, cf. Appendix
Key clinical results supporting potential entry into Phase 3
Consistent results obtained in 210 people with T1D & T2D across common administration devices Repeated administration in T1D (solid meal test; March 14, 2016 ; NCT02528396, 36
patients) 31% reduction in blood glucose excursion over first 2 hours vs. Humalog injected at
mealtime at beginning of treatment 42% reduction at end of treatment Repeated administration in T2D (solid meal test; April 27, 2016; NCT02562326, 51
patients) 22% reduction in blood glucose excursion over first 2 hours vs. Humalog injected at
mealtime Insulin pump therapy in T1D (solid meal test; December 15, 2016; NCT02562313, 44
patients) Acceleration demonstrated in 2 pumps & insulin syringe compared to Humalog
injected at mealtime Pilot bioequivalence (BE) study U200/U100 (December 11, 2015; NCT02529293, 26
volunteers) Predefined criteria for BE were met
Study in healthy Japanese subjects (May 31, 2016; NCT02660502, 15 patients) Confirmed BC Lispro PK/PD profile, allowing Japanese patients inclusion in Phase 3
March 2017 17
BC LISPRO
A true combination of two gold standard insulins - glargine as basal and lispro as prandial
March 2017 18
BC COMBO
Insulin lisproHumalog®
Insulin glargineLantus®
BioChaperone® COMBO
6 10 14
18
22 2 6
6 10 14
18
22 2 6
6 10 14
18
22 2 6
6 10 14
18
22 2 6
Once-a-day
Twice-a-day
6 10 14
18
22 2 6
vs. Premix insulin
Twice-a-day
+ =
Schematic PK representations
Adocia is developing a simple 2-in-1 option for tight basal and prandial control
March 2017 19
BC COMBO
As simple as premix with better control and less hypoglycemia
Less injections than Basal/Bolus with similar control
One co-pay and use of “off-patent” insulins
Potential benefits*
BioChaperone® Gla Lispro(BC Combo)
*As demonstrated clinically by the only comparable approved product, Ryzodeg (Novo Nordisk)
$5BPremix insulin market (2015)1
1 Source: Adocia estimates based on major companies annual reports, 2015
BC Combo has shown superior prandial and basal control compared to premix insulin in people with T1D
March 2017 20
BC COMBO T1D
In T1D, BC Combo showed vs. HumalogMix 75/25:
Less hyperglycemia (faster-acting) Less hypoglycemia (lower late prandial
effect) Potential for once-a-day administration (24h
basal action in a clamp trial) with most major meal coverage
BGmin +30%2
Less hypo
Individualized doses
∆AUC0-2h -24%1
Less hyper
Trial in 28 people with T1D (NCT#02514954); 1 p=3.10-3;2 p=8.10-3 These results were presented by Dr Steve Edelman (UCSD) during the 76th Scientific Sessions of the American Diabetes Association (June 2016).
Post-meal glycemia in T1D
Liquid meal+ Insulin s.c.
For more detailed results, cf. Appendix
BC Combo 75/25 confirmed its promising profile compared to premix insulin in people with T2D
March 2017 21
BC COMBO T2DM
Trial in 24 people with T2D (NCT#02514850).These results were the subject of poster commented by Dr Eda Cengiz (Yale School of Medicine) during the 76th Scientific Sessions of the American Diabetes Association (June 2016).
Glucose Infusion Rate in T2D (clamp) BC Combo has the potential to offer competitive pricing compared to Novo Nordisk’s Ryzodeg®
Program to achieve ready-to-phase 3 stage to reach next inflexion point
3 successful clinical studies (T1D & T2D)
Ongoing meal-test study in T2D Results expected Q2 17
Planned dose-response study in T1DExpected to start Q2 17
Planned Outpatient study in T2DExpected to start Q4 17
Fast 24hr +
Sharp transition
For more detailed results, cf. Appendix
Adocia intends to deliver affordable prandial insulin to price-sensitive populations
March 2017 22
HINSBET
Affordable prandial insulin
Dosing closer to mealtime
Potential benefitsHinsBet® U100
HinsBet® U500
$1BHuman prandial insulin market (2015)1
1 Source: Adocia estimates based on major companies annual reports, 2015
HinsBet displays similar early action to fast-acting insulin analog in T1D patients
March 2017 23
HINSBET
Early Glucose Infusion Rate (U100)
PK/PD clinical trial in 36 subjects with type 1 diabetes (NCT#02213146).
Meal-test study in 36 T1D confirmed PD profile in first hour1 (Oct 2016)
During first hour after the meal, HinsBet: Significantly reduced glucose
excursion vs Humulin (p=0.0002) Was not significantly different
from Humalog (p=0.5373) Exploring licensing options in emerging
markets1Meal-test study in 36 subjects with type 1 diabetes (NCT#02739906). Subjects received individualized single doses of HinsBet, regular human insulin (Humulin) and rapid-acting analog insulin lispro (Humalog) immediately before ingesting a standardized mixed meal. Detailed results remain under embargo until publication at a major diabetes conference.
NEW PROGRAMS
March 2017 24
How to potentialize insulin action?
March 2017 25
MULTI-HORMONA
L
Insulin
Glucagon
GLP-1 Amylin
In combination
BC Glargine GLP-1BC Lispro PramlintideBC Lispro Exenatide
In a dual-chamber pump
BC Glucagon + Insulin
Efficacy
Safety
Among a multitude of metabolic hormones, 4 classes have been approved for the treatment of diabetes
March 2017 26
DIABETES
Pancreas Produces insulin, amylin & glucagon
IntestinesProduce GLP-1
Multiple targets of action of: insulin amylin (pramlintide) GLP1 (GLP1-RA) glucagon
In healthy people, a time-sensitive hormonal pattern maintains normoglycemia
March 2017 27
DIABETES
0 1 2 3 4 5 6
Insulin
Amylin
Glucagon
GLP-1
Meal
0 1 2 3 4 5 6
Meal
InsulinAmylin
Glucagon
GLP-1
Healthy With Type 1 diabetes (T1D)
Time
Leve
l of s
ecre
tion
(rel
ative
scal
e)
In T1D, hormonal pattern is severely disrupted
Insulin, Amylin and GLP-1 are secreted
X Glucagon is suppressed
Schematic representation of hormonal pattern1
1 Source: Adocia, adapted from Toff-Neilsen et al, J. Clin Endocrinol Metab 2001;86:3717-3723; Cummings DE et al, Diabetes 2001;50:1714-1719; Aronoff SL et al , Diabetes Spectrum 2004; 17(3): 183-190
People with T1D need multi-hormonal treatment to improve long-term outcomes
Industry focused on developing multi-hormonal treatments for T2D
Established benefit of hormonal combinations in T2D
T1D are insulin, amylin and GLP1-deficient Insulin alone is life-saving, but insufficient to prevent
long-term complications despite optimal use Pramlintide is the only other hormone approved for
T1D, but puts disproportionate burden on patients (up to 7+ injections/day total)
No combination is approved for T1D
Tighter glycemic control lowers the risk of severe complications1
March 2017 28
BC PRANDIAL COMBOS
Complications1
heart disease, retinopathy, nephropathy,
blindness, amputations…
36%3 of children with
T1D are overweight or obese
65%2 of US adults with
T1D are overweight or obese
1 DTTC study, NEJM, 1993, 329(14); EDIC study NEJM, 2005, 353(25) 2 Conway et al, Diabetes Med 2010 April; 27(4):398-404. BMI>25, Data for 2004-2007 period. 3Du Bose et al, J Ped 2015, data for Germany & the USA, WHO BMI categories.
Glucagon is needed to address hypoglycemia
Insulin prevents hyperglycemia (e.g. after meals)
Glucagon prevents hypoglycemia (e.g. during exercise) by raising the blood glucose level
Human glucagon is the only approved rescue treatment against severe hypoglycemia
But human glucagon is unstable in solution requiring reconstitution of lyophilized product in emergency situations
A ready-to-use aqueous solution of human glucagon is needed to improve treatment of hypoglycemia
March 2017 29
BC GLUCAGON
Bloo
d gl
ucos
e co
ncen
tratio
n
INSULIN
GLUCAGON
Adocia aims to greatly enhance insulin pump therapy with stable and soluble human glucagon
March 2017 30
BC GLUCAGON
* For illustration purposes only
Relieve patient from risk of hypoglycemia, especially at night
More time-in-range (less hypoglycemia & less hyperglycemia)
More freedom to live “normal” everyday life
Potential benefits
BioChaperone® Human Glucagon
DHAP : Dual-hormone artificial pancreas Automated administration of insulin and glucagon
under continuous glucose monitoring (CGM)
CGMInsulin
Glucagon
*
*
DHAP is a promising system to achieve truly automated closed-loop glycemic control
March 2017 31
BC GLUCAGON
Insulin only (CSII)
Bionic pancreas(DHAP)
Significantly improved control with BetaBionics Ilet dual-chamber system (insulin + reconstituted Lilly Glucagon®) in pilot clinical study :
Better glycemic control, less intrasubject and intersubject variability compared to usual care
Less hypoglycemia than usual care Achieved in the home setting, meal announcements were optional. Device worn
24h/day for 11 days.El Khatib et al, 77-OR, ADA 76th Scientific Sessions June 10-14th 2016, USA. Multicenter, randomized, CSII-controlled clinical trial in 39 adults with T1D. Russell et al, The Lancet (2016) 4(3):233-243
39 individual CGM traces (T1D)
Adocia develops an aqueous human glucagon for use in a DHAP system
BC Human Glucagon showed similar action on blood glucose compared to Glucagen® during the first 3 hours in preclinical studies
BC Human Glucagon is soluble and stable at pH 7
3 weeks stability at 37°C Development of standard
concentration (1 mg/mL) for rescue and more concentrated formulations for DHAP
First-in-man study expected to start in Q2 2017
March 2017 32
BC GLUCAGON
N=7 pigs. Cross-over design BC Glucagon (1 mg/mL) vs. GlucaGen® (Novo Nordisk, 1 mg/mL, reconstituted ex-temporane.)
60
80
100
120
140
160
180
0 20 40 60 80 100 120 140 160 180
G001
G014, W37-16
Mean blood glucose (pigs)
0
20
40
60
80
100
120
140
160
180
0 20 40 60 80 100 120 140 160 180
Glucagen 1 µg/kgBC Glucagon 1 mg/mL 1µg/kg
0
20
40
60
80
100
120
140
160
180
0 20 40 60 80 100 120 140 160 180
Glucagen 1 µg/kgBC Glucagon 1 mg/mL 1µg/kg
0
20
40
60
80
100
120
140
160
180
0 20 40 60 80 100 120 140 160 180
Glucagen 1 µg/kgBC Glucagon 1 mg/mL 1µg/kg
Adocia is developing efficient and affordable intensification options over basal insulin for T2D
March 2017 33
BC GLAR GLP-
1
Better control than basal alone
Fewer side effects than each product separately
Weight neutral
Only 1 daily injection
Potential benefits*BioChaperone® Glargine Dulaglutide
BioChaperone® Glargine Liraglutide*As demonstrated clinically by approved products Xultophy® (IDegLira) & Soliqua® (IGlarLixi)
$7BForecasted Basal-GLP1
market (2019-2020)1
1 Source: Leerink forecasts, October 6, 2016
Two injectable combos for better and/or more affordable intensification options in T2D
Adocia is currently developing 2 products: BC Glargine Liraglutide, potential for
competitive pricing, based on use of off-patent proteins
BC Glargine Dulaglutide, potential for best-in-class performance, based on excellent profile of dulaglutide and glargine.
First stability and preclinical results are promising
First-in-man study expected on one product to start in 2017, based on positive CMC & preclinical results
March 2017 34
50%1Patients on
basal insulin are not
adequately controlled1
« All-in-1 »
1 product 1 injection 1 co-pay
Xultophy® (IDegLira, NVO)
& Suliqua®/Soliqua® (IGlarLixi, SAN) approved in EU & US (2016)
1 Sanofi, JP Morgan Healthcare Conference Presentation , San Francisco, January 12, 2015.
BC GLAR GLP-
1
Enabling new prandial insulin combinations with already proven medical benefits
March 2017 35
BC LISPRO COMBOS
Better control than prandial insulin alone
Weight loss or weight neutrality
Fewer side effects than each product separately
No increase in injection burden
Potential benefits*BioChaperone® Lispro Pramlintide
BioChaperone® Lispro Exenatide*As demonstrated clinically by co-administration of approved products insulin & pramlintide in people with T1D and insulin & exenatide in people with T2D
-25-20-15-10
-50
Change in prandial insulin dose after 6
months (%)
Pramlintide (TID) clinically proven synergistic benefits with mealtime insulin in people with T1D
March 2017
PRAMLINTIDE
36
Guthrie R et al Diabetes 2005, 54(Suppl 1):A118 T1D, N = 265 at baseline; 6-month data; mean (SE);
*: P <.05. See also Pullman J et al Vasc Health Risk Manag. 2006, 2 (3), 203-212. and in T2D only: Karl D, et al. Diabetes Technol Ther 2007; 9(2):191-199 .
-3.5-3
-2.5-2
-1.5-1
-0.50
Change in weight after 6 months (kg)
-22%*
-0.2%*
-3 kg*
Blood glucose control (T1D)
Adocia intends to develop easy-to-use combinations of insulin/pramlintide for people with T1D
Prandial suppression of glucagon
Slowed gastric emptying
Appetite reduction-0.2%*
Exenatide on top of prandial insulin in T1D has shown:
Improved glycemic control Insulin dose reduction of 20%
GLP-1 have also demonstrated both in T1D and in T2D:
Reduction in HbA1c after 6 months Weight loss compared to insulin alone Fewer side effects, especially hypoglycemia
Delta glucose in blood after a mixed meal150
100
50
0
-50
-1000 100 200 300
Delta
glu
cose
(mg/
dL)
insulininsulin + exenatide 1.25µginsulin + exenatide 2.5µg
Time (min)
Exenatide clinically proven synergistic benefits with mealtime insulin in people with T1D
March 2017
EXENATIDE
37
Adapted from Raman VS, et al. Diabetes Care 2010 Jun; 33(6): 1294-1296.
Pediatric patients with T1D on MDI (N = 8) received BYETTA (exenatide) 1.25 and 2.5 mcg pre-meal adjunctive to prandial insulin. Glycaemia was analyzed for 6 hours post-meal.
Adocia to develop easy-to-use combinations of insulin/GLP-1 for people with T1D
Unlocking the potential of prandial insulin combinations
March 2017 38
BC LISPRO COMBOS
Prandial Insulin (Lispro)
Pramlintideor
Exenatide
3 injections/day
2 or 3 injections/day
Increases glucose disposal
Modulate glucose appearance
+ BioChaperone
unmixable
BioChaperone Lispro Combos
3 injections/day or CSI
BC Lispro Combos may restore the synergistic benefits of prandial hormones for people with T1D
BC Lispro Combos are potentially affordable options based on mature proteins:
BioChaperone has demonstrated ability to stabilize these combinations in aqueous solution against fibrillation at 4°C and 37°C.
BC Lispro Combos could be administered from a pen or a pump Pump use may mimic normal physiology even more closely Emerging T2D-friendly pumps may facilitate expanded use of BC Lispro Combos in
T2D populationMarch 2017 39
BC LISPRO COMBOS
Insulin lispro + PramlintideInsulin lispro + Exenatide
Key financial elements
March 2017 40
ADOCIA
Shareholders’ equity (November 30, 2016)
Listed on Euronext Paris (ADOC)
6.9M shares outstanding ADR program in the US
(ADOCY) Well capitalized €58M cash
position (December 31, 2016) €85M raised since inception Long term debt:
€0.9M loan from BPI France (refundable in case of success)
€6.1M bank loan for purchase of Lyon headquarters building
Analysts
Leerink (Seamus Fernandez)Jefferies (Peter Welford)Kepler Market (Arsène Guekam)Invest Securities (Martial Descoutures)Oddo (Sébatien Malafosse – Pierre Corby)Louis Capital Partners (Pierre Vaurice)
Financial summary
Soula Family 22.0 %
Free Float (*)60.3%
BPI 10.8%
Sham 4.7%
Viveris 1.0%Oréo Finance 0.6%Key managers 0.6%
(*) including US investors from March, 2015 private placement of 10% of the capital (KKR, Alken, BVF and others)
Expected upcoming catalysts
March 2017 41
ADOCIA
BC LISPRO Phase 3-ready asset to be partnered
BC COMBO Ongoing Phase 2a study in T2D results : Q2
17 Planned dose-response study in T1D: to
start Q2 17 Planned outpatient study in T2D: to start
Q4 17
HINSBET Looking for a partner in regional markets
BC HUMAN GLUCAGON First-in-man study : Q2 2017
BC GLARGINE DULA & BC GLARGINE LIRA
First-in-man study : 2017
BC LISPRO PRAMLINTIDE & BC LISPRO EXENATIDE
First-in-man study : Q4 17
Clinical programs Preclinical programs
APPENDIX
March 2017 42
Adocia is supported by a top-tier Medical Advisory Board
12 highly renowned international thought-leaders: Dr. Jay Skyler, MD, Chairman, University of Miami (US) Dr. Vanita Aroda, MD, MedStar Health Research Institute (US) Dr. Bruce Bode, MD, Emory University (US) Dr. John Buse, MD, PhD, University of North Carolina (US) Dr. William Cefalu, MD, Louisiana State University (US) Dr. Steven V. Edelman, MD, University of California at San Diego (US) Dr. Dan Einhorn, MD, University of California at San Diego (US) Dr. Vivian Fonseca, MD, Tulane University (US) Dr. Irl Hirsch, MD, University of Washington (US) Dr. Chantal Mathieu, MD, University Hospital of Leuven (Belgium) Dr. Thomas Pieber, MD, Medical University of Graz (Austria) Prof. Denis Raccah, MD, PhD, APHM (France)
March 2017 43
ADOCIA
Results summary compared to Humalog U100 in T1DM subjects
March 2017 44
BC LISPRO
BioChaperone Lispro in comparison with Humalog showed:
Faster absorption Faster-in (Early t[50%max],
tmax, AUC0-30min) Faster-out (Late t[50%max],
AUC2-8h) Similar total exposure
Reduced post prandial glucose excursions
61% PPG reduction over the first two hours
Reduction of blood glucose by 42 mg/dL at 1 hour
Similar safety profile at single dose conditions based on local tolerance and number of hypoglycemic events
Comprehensive work to further evaluate BioChaperone Lispro ongoing, including a concentrated U200 formulation
Biochaperone Lispro: Shorter TMAX, Higher CMAX
and Similar ExposureGreater Earlier Exposure: Faster In
Lower Late Exposure: Faster Out Better Post Prandial Glucose Control
GeoLSMBC
Lispro
GeoLSMHumalog
Ratio [95%CI]BC Lispro/Humalog
Tmax (min) 47 62 0.75 [0.69; 0.83]Cmax (mU/L) 117 104 1.13 [1.06; 1.20]AUC0-8h (h*mU/L)
256 254 1.01 [0.97; 1.05]
GeoLSMBC
Lispro
GeoLSMHumalog
Ratio [95%CI]BC Lispro/Humalog
Early t[50%max] (min)
18 29 0.63 [0.57; 0.70]
AUC0-30min (h*mU/L)
23 9 2.68 [2.18; 3.30]
AUC0-1h (h*mU/L) 76 50 1.52 [1.37; 1.67]
GeoLSMBC
Lispro
GeoLSMHumalog
Ratio [95%CI]BC Lispro/Humalog
Late t[50%max] (min)
135 160 0.85 [0.78; 0.91]
AUC2-8h (h*mU/L)
84 106 0.79 [ 0.72; 0.87]
BC Lispro Humalog Mean Difference
BG1h (mg/dL) 135 177 42BG2h (mg/dL) 126 153 27
294-OR in Novel Therapeutics in T1D, June 13, 2016, 76th ADA Scientific Sessions
Results summary compared to Conventional Lispro Mix 75/25 in T1DM subjects
March 2017 45
BC COMBO
In this solid mixed meal study, BC Combo achieved more effective PPG control than lispro Mix:
Improved post-prandial blood glucose control
24% reduction in ΔAUCBG_0-2h
23 mg/dL decrease in maximum BG
24 mg/dL mean BG reduction at 1hr
Lower risk for delayed prandial hypoglycaemia
Less subjects with low BG < 63 mg/dL and 50 mg/dL
Less time spent in hypoglycaemia and more time spent in target glycaemia
Potential of BC Combo to improve post-prandial glucose control and lower risk of both hyperglycaemic and hypoglycaemic excursions will be investigated in further clinical studies
Mean Unadjusted BG Profiles ± SEM Over 6hr After s.c. Administration of Individualised Doses of BC
Combo and Lispro Mix
Cumulative Percentage of Subjects With BG Values < 63 mg/dL (A) or < 50 mg/mL (B) Over
the Course of the Meal Test
Demographic and Baseline Characteristics of the Study PopulationParameter Mean ± SD Parameter Mean ± SD
SexFemale: n-6
(21.4%)Male: n-22
(78.6%)
Diabetes Duration (years)
27.2 ± 11.5
Race White 100% BMI (kg/m2) 24.2 ± 2.1
Age (years) 45.9 ± 11.2 C-Peptide (nmol/L) 0
Height (cm) 177 ± 8 HbA1c (%) 7.33 ± 0.80
Weight (kg) 76 ± 10 30 subjects screened, 28 randomised, 28 received lisproMix – 27 received BC Combo Full analysis set n=28: 27 BC Combo – 27 lispro Mix (1 exclusion due to wrong dosing)
Parameter BC Combo
Lispro Mix
P-value
Subjects with at least one
hypoglycaemic event7 / 27 15 / 28 0.03641
Number of hypoglycaemic
events12 29 0.00791
Number of hypoglycaemic
event per subject02 12 0.01513
Hypoglycaemic events
1 Chi-Square test
2 Median 3 Wilcoxon Signed Rank test
295-OR in Novel Therapeutics in T1D, June 13, 2016, 76th ADA Scientific Sessions
Results summary compared to Humalog 75/25 in T2DM subjects
March 2017 46
BC COMBO
In this study, BC Combo demonstrated:
Greater early glucodynamic effect in first hour post dosing and faster time to maximum blood glucose lowering which is essential to achieve better post prandial blood glucose control
Lower late post prandial effect in comparison to Humalog Mix 75/25 which may reduce the risk of delayed post-prandial hypoglycaemia as shown in a meal test study in subjects with T1DM (ADA2016 OR-295)
Higher late basal effect than Humalog Mix 75/25, similar to the separate injections, indicating that BC Combo could adequately provide both basal and prandial insulin requirements for a meal with only one injection per day
The results obtained in T2DM subjects replicate our findings in subjects with T1DM by demonstrating BC Combo’s favorable time-action profile over Humalog Mix 75/25
Smoothed GIR Profiles (0-30h) of 0.8 U/kg BioChaperone Combo, 0.8 U/kg HumalogMix 75/25
and Separate Injections of 0.2 U/kg Lispro + 0.6 U/kg Glargine
Smoothed GIR Profiles (0-2h) of 0.8 U/kg BioChaperone Combo, 0.8 U/kg HumalogMix 75/25 and Separate Injections of 0.2 U/kg
Lispro + 0.6 U/kg Glargine
PD Parameters Based on Glucose Infusion RateBC Combo Humalog Mix 75/25 P-value vs. BC
ComboLispro _ glargine P-value vs. BC
ComboPramdial Phase (0.6h)AUCGIR 0-1h [mg/kg] 88 (74) 29 (34) <0.0001 58 (48) 0.0087AUCGIR 0-2h [mg/kg] 294 (227) 174 (126) 0.0001 277 (184) 0.5227AUCGIR 0-6h [mg/kg] 860 (536) 1011 (535) 0.0335 1121 (556) 0.0003TGIRmax [h] 1.3 [1.2;5.1] 3.8 [1.8;6.0] <0.0001 2.9 [1.4;4.9] 0.0057Prandial – Basal Transition (6-12h)AUCGIR 6-12h [mg/kg] 589 (275) 870 (501) 0.0002 630 (211) 0.3420AUCGIR 6-24h [mg/kg] 1075 (615) 1481 (911) 0.0001 1156 (551) 0.4522Basal Phase (12-30h)AUCGIR 12-18h [mg/kg] 342 (225) 473 (354) 0.0063 382 (221) 0.2156AUCGIR 24-30h [mg/kg] 186 (133) 99 (102) 0.0105 174 (139) 0.6747OverallAUCGIR 0-30h [mg/kg] 2122 (1184) 2590 (1368) 0.0103 2451 (1071) 0.0124Table shows arithmetic means (SD) except median [min;max] for TGIRmaxP-value from Hodges and Lehmann Estimates or (for AUCGIR 0-6h and AUCGIR 0-
30h) from LS Means
942-P in 12-B Clinical Therapeutics/ New Technology-Insulins, June 11, 2016, 76th ADA Scientific Sessions
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