R&D DAY 2019 - Cosmo Pharma28 R&D Day 2019 A set of endoscopy procedures were recorded annotating...

Cosmo Pharmaceuticals

R&D DAY2019


SA FE H A R B OU R

This presentation may include forward-looking statements that are based on our management’s beliefs andassumptions and on information currently available to our management.The inclusion of forward-looking statements should not be regarded as a representation by Cosmo that any ofits plans will be achieved. Actual results may differ materially from those set forth in this presentation due to therisks and uncertainties inherent in Cosmo’s ability to develop and expand its business, successfully completedevelopment of its current product candidates and current and future collaborations for the development andcommercialization of its product candidates and reduce costs (including staff costs), the market for drugs to treatIBD diseases, Cosmo’s anticipated future revenues, capital expenditures and financial resources and othersimilar statements, may be “forward-looking” and as such involve risks and uncertainties and risks related to thecollaboration between Partners and Cosmo, including the potential for delays in the development programs forits products. No assurance can be given that the results anticipated in such forward looking statements willoccur. Actual events or results may differ materially from Cosmo’s expectations due to factors which include, butare not limited to, increased competition, Cosmo’s ability to finance expansion plans, the results of Cosmo’sresearch and development activities, the success of Cosmo’s products, regulatory, legislative and judicialdevelopments or changes in market and/or overall economic conditions. Cosmo assumes no responsibility toupdate forward-looking statements or to adapt them to future events or developments.

You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of thedate hereof, and Cosmo undertakes no obligation to revise or update this presentation.

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A G EN D A

01 WELCOME AND INTRODUCTIONMauro Ajani, Chairman

02 COMPANY PERSPECTIVES AND STRATEGYAlessandro Della Chà, CEO

03 ARTIFICIAL INTELLIGENCE IN COLONOSCOPY: OUR NEW DEVICE IN PLAYNhan Ngo Dinh, Head of Research and Development Cosmo AIAndrea Cherubini, Head of Artificial Intelligence Cosmo AI

04 AEMCOLO: A NOVEL MARKETING APPROACHSean MacDonald, Head of Business Development

05 NEW PRODUCTS IN THE PIPELINEProf. Michele Maio, Director of Immuno-oncology Center, University of SienaMara Gerloni, CSO Bellatrix

06 WRAP-UP AND Q&AAlessandro Della Chà, CEO

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WELCOME AND INTRODUCTION

M A U R O A J A N I , C H A I R M A N

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COMPANY PERSPECTIVES AND STRATEGY

A L E S S A N D R O D E L L A C H À , C E O

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COSMO: MOVING FORWARD FULL THROTTLE!

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C O SM O : L AT EST N EW S S I N C E R EL EA SE O F F U L L Y2018 F I N A N C I A L S

• Unveiling of the Artificial Intelligence product and subsequent worldwide validation deal with Medtronic

• Distribution deal of Eleview with Medtronic for US, China and South America

• Collaboration Agreement with Medtronic in AI

• Submission of ByfavoTM (Remimazolam) NDA

• Acceptance of IND for new oncologic product

• Completion of Aries restructuring, savings of approx. € 20m in 2019

• Very positive results of Breezula full Phase II clinical trial

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C O SM O : A H I G H LY D I VER SI F I ED O R G A N I Z AT I O N

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Cosmo is a sum of different business and assets, a complex organization whose aim is to efficiently develop and manage assets while reducing overall risks

Contract manufacturing

(APPROVED FOR TD, PHASE II IBS-D ONGOING)

45% STAKE

AI(APPROVED IN EU, US

REGULATORY PATHWAY UNDERGOING)

(SECOND PHASE III TRIAL UNDER DESIGN)

CB-03-10

(IND ACCEPTED)(NDA SUBMITTED)


C O SM O ’ S ST R AT EG Y G O I N G F O RWA R DM A XIM IZ E R ET U R N S W H IL E M IN IM IZ IN G R ISK S

THE A I PARTNERSHIP WITH MEDTRONIC• Territory: worldwide• Distribution agreement including supply• Estimated Net Margin for Cosmo expected above

20%• Devices currently being deployed with EU KOLs to

prepare commercial launch• EU Sales expected to start 2H 2019• US sales expected to begin 2020, upon FDA

approval• Medtronic established business model: user fees• Estimated yearly fee per device in US/EU:

USD/€ 36.000• Estimated number of colonoscopes in the US:

20.000

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OUR REVENUES ARE PROFITS

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Stop direct distribution of medical devices in the US, with Medtronic as

partner of choice

New US distribution agreement (including

supply) with Medtronicfor Eleview extended to

China and South America

Estimated Net Margin for Cosmo expected above

20%



Position Cosmo US commercial organizationon an opportunity-by-opportunity basis

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Aemcolo: pursue new direct marketing strategy that allows maximizing sales without field sales force

ByfavoTM: pursue NDA approval

CB-03-10: conduct phase I in humans and partner subsequent development with high-standing player

Methylene Blue MMX:reach agreement with FDA re additional phase III trial and start such trial


ARTIFICIAL INTELLIGENCE IN COLONOSCOPY:

OUR NEW DEVICE IN PLAYNHAN NGO DINH, HEAD OF RESEARCH AND DEVELOPMENT COSMO AI

ANDREA CHERUBINI, HEAD OF ARTIFICIAL INTELLIGENCE COSMO AI

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C O SM O A I R & D T EA M

Nhan Ngo DinhHead of Research and Development

More than 16 years experience in hardware and software development of IT medical systems and management of biomedical data in radiology, neurology, nuclear medicine, gastroenterology, medical photography and cardiology. Together with his team he has successfully developed innovative hardware and software solutions for hospitals, CROs, Pharma and Biotech companies.

Andrea Cherubini Head of Artificial Intelligence and Machine LearningHe has been a Lecturer of Applied Physics and a member of Italian National Research Council, with research interests in image processing and Computer Aided Diagnosis. He has published over 100 articles in peer-reviewed journals and conference proceedings. He is reviewer for several prestigious journals and international conferences in the field.

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Giulio EvangelistiHead of Production and Delivery

More than 16 years experience in hardware and software delivery to hospitals, CROs, Pharma and Biotech companies. Together with his team he has successfully managed the full stack of processes related to deployment and support of products and services to global customers.


PR OJEC T H I STO RY

Dawn of AI ProjectCosmo takes the opportunity of MB-MMX trial to develop the first HD lossless video database of colonoscopies in the world

Challenges of AIR&D team tests several system architectures, software and hardware requirements. First AI models are tested in laboratory and in the field. Novel approaches are developed

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Gear shiftAI network finalized, training model finalized, encouraging field results

Game changesExcellent results and reproducibility in field results, ultra-high True Positive Rate, ultra-low False Positive RatePatents Filed

2013 2015 2017 2018

Linkverse produces the ad-hoc recording devices and the cloud platform dedicated to this serviceLinkverse follows project on Computer Vision and Machine Learning in dermatology and neurology


C O L O N O SC O PY F O R SC R EEN I N G C R C

• Colorectal Cancer is the second and third-leading cause of cancer related deaths in men and women, respectively

• Screening colonoscopy has allowed for a reduction in the incidence of mortality of CRC via the detection and removal of adenomatous polyps

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1. Corley DA et al. 2014. N Engl J Med (370):1298–306

1% increase in Adenoma Detection Rate

is associated with1

3% decrease in the risk of interval CRC


M ISS IN G POLYPS

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• Reported miss rates are between 20% and 40%, due to both polyp and operator characteristics1,2

• Several studies3,4 have shown that assistance by a second observer increases the polyp detection rate

1. Mahmud N et al. 2015. Gastroenterol Rep 179–842. Ahn SB et al. 2012. Gut Liver (6):64–703. Aslanian HR et al. 2013. Am J Gastroenterol: (108)166–724. Lee CK et al. 2011. Gastrointest Endosc: (74) 1094–102

A real-time automatic polyp detectionsystem will assist the endoscopist in a more consistent and reliable way than a human assistant


C O M PU T ER A SSI ST ED D I A G N O SI S

• Computer Assisted Diagnosis (CAD) are a class of systems providing decision support to physicians

• A subgroup of CADs are implemented with Deep Learning

• Deep Learning relies on artificial neural networks that are biologically inspired by the concept of neurons and synapses in the brain

• Contrary to Machine Learning, Deep Learning does not require hard coded definition of features to detect in images, allowing for continuous improvement

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PR OD U C T PR ESEN TATION

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D EEP LEARNING

• Artificial Intelligence supervised algorithms are able to learn from example, using labeled data

• Performances of AI algorithm are heavily influenced by the quality of the dataset

• Large numbers of examples permit the AI to learn all the possible variations encountered in the real world

• High quality images permit the AI to learn the important features that distinguish the signal from the noise (e.g. polyps from healthy tissue)

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B EST D ATA SET I N T H E W O R L D

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• CB-17-08 has been trained using Cosmo’s unique proprietary library of high definition, lossless colonoscopy videos gathered in the clinical trials of MB MMX

• For the first time a large (over 1000 patients) number of colonoscopies were recorded in an international, multi-center study

• These procedures were performed by some of the best endoscopists in the world, with an average ADR of 47% in white light


A D VA N TA G ES O F O U R D ATA SET

HD lossless videos from multiple different scopes

Large, international population

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Extremely high ADR

N=30

optimal AI learning conditionsagnostic to endoscopy unit

unbiased distribution of both patientsand polyps clinical characteristics

database contains a large proportionof most challenging to detect polyps

(e.g. small and flat)


D ATA SET INCREASE STEPS

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01 HUNDREDSFirst Dataset

First set of images used for AI algorithm development comprised 500 images of “easy to detect” polyps (Q1 2017)

02 THOUSANDSDataset with improved annotation procedure

Size of dataset in Q1 2018 was 15000 images from the MB-MMX clinical study

03 HUNDREDS OF THOUSANDSStable Release of Dataset Sep 2018

Size of dataset frozen at Sep 2018 for regulatory path is over 700.000 images of polyps recorded in white light on different endoscopes in Europe, America and Asia

04 TENTHS OF MILLIONSDataset Continuous Improvement (ongoing)

We are currently recording new data with a novel protocol to be used with improved AI and for new features


VID EO

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SENSITIVITYTRUE POSITIVE RATE PER-POLYP

99.7%

FI NDING ALL THE LES IONS DETECTED BY TOP EN D OSC OPISTS

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A set of endoscopy procedures were recorded annotating the presence of all polyps, together with all relevant details, including histology. Endoscopistsperforming procedures were featuring an ADR of 47% in white light

Recorded videos were read by CB-17-08 and related findings were compared to endoscopists findings


A I A L ER T F R EQ U EN C Y I S N O T A N U I SA N C E F O R EN D OSC OPISTS

29

False activations have been calculated with the consensus of a panel of endoscopists reviewing all activations of CB-17-08 in recorded videos

The extremely low amount of false activations is not disturbing the procedure, it does not slow down or alter negatively the conventional endoscopy procedure

ACTIVATION NOISEFALSE POSITIVES FRAMES IN A FULL PROCEDURE

0.9%

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FURTHER R & D D EVEL O PM EN T S

• Product will improve constantly through the distribution of new releases on a regular basis

• New core functionalities already under development (e.g. Virtual Biopsy)

• Additional GI applications under development (IBD and Gastro)

• Additional features beneficial to patients and physicians under development

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N EXT STEPS

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Device is already approved in EU

Device will be presented at DDW next week

Expected US market entry Q1 2020

Distribution to European KOLs is ongoing

FDA regulatory path underway


AEMCOLO: A NOVEL MARKETING APPROACH

S E A N M A C D O N A L D , H E A D O F B U S I N E S S D E V E L O P M E N T

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A EM C O L O : N OW A PPR OVED F OR TRAVELERS’ D I A R R H EA

Approved in US for Travelers’ Diarrhea Nov. 2018

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A EM C O L O – STR ON G FU TU R E TH R OU GH A D D IT ION A L IN D IC AT ION S

• New formulation in multicenter phase II clinicaltrial in Europe for IBS-D

• Further development ongoing/being initiated in: • Minimal Hepatic Encephalopathy

• IND and study protocol accepted by FDA• Study close to initiation

• Acute Uncomplicated Diverticulitis• Protocol under development

• Small Intestine Bacterial Overgrowth (SIBO)• Protocol under development

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A EM C O L O : PER F EC T LY TA IL OR ED F OR T R AVEL ER S’ D IA R R H EA 1, 2

• Non-systemic, minimally absorbed

• MMX® delivery to the colon

• Proven efficacy against E. coli

• Reliable safety and tolerability

• Simple BID dosing

• No increase in ESBL-E colonization rates/lower risk of acquisition

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AEMCOLO OFFERS A CURE TO TRAVELERS’ DIARRHEA

ELIMINATING THE SHORTCOMINGS OF OTHER TREATMENTS

1. DuPont, HL, et al. Targeting of Rifamycin SV to the Colon for Treatment of Travelers’ Diarrhea: A Randomized, Double-Blind, Placebo-Controlled Phase 3 Study, Journal of Travel Medicine, Vol. 21:369–376, 2014. 2. Steffen, R, et al, Rifamycin SV-MMX® for treatment of Travelers’ diarrhea: equally effective as ciprofloxacin and not associated with the acquisition of multi-drug resistant bacteria, Journal of Travel Medicine, 2018, published online ahead of print, Accessed Dec 9, 2018


A EM C O L O FOR TRAVELERS’ D I A R R H EA : N OW R EC OM M EN D ED B Y T H E INTERNATIONAL SOCIETY OF TRAVEL M ED IC I N E ( I ST M )

“In conclusion, no single drug is perfect against Traveler's diarrhea. We rate the advantages of non-absorbed antibiotics — reduced risk of adverse events, improvement in disease in most patients with illness, reduced risk of acquisition of multiple drug resistant organisms (so far demonstrated only for Rifamycin SV-MMX®) and lastly protection of systemic antibiotics against resistance — greater as compared to the disadvantages such as personal harm and public health impact that a small minority of Traveler's diarrhea patients with invasive illness would not be initially treated by a systemic antibiotic as first line drug from a travel kit for self-treatment.”

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A EM C O L O FOR TRAVELERS’ D I A R R H EA : SU PPOR T ED B Y T H E F D A

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TRAVELERS’ D I A R R H EA IS TRADIT IONALLY CONSIDERED A SM ALL M ARKET

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IS IT TRUE?


Population of Canada37M

Population of Benelux28M

Population of Switzerland8.4M

Entire US population with IBD3M

TRAVELERS’ D I A R R H EA IS A HUGE HUGE HUGE M A R K ET

39

Number of Americans traveling EVERY YEAR to at risk

countries where the ISTM recommends bringing an antibiotic with them

46 Million

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TRAVELERS’ D I A R R H EA : H OW TO C A PT U R E T H E OPPOR T U N IT Y

• Targeting Travelers rather than patients requires a different approach

• The Travelers’ Diarrhea market cannot be approached with the traditional means because most Travelers do not typically visit their doctor prior to departure

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Need to target the Travelers while they’re making plans, and make it

easy to get the product


8.7 billion minutes (+41% Y/Y)spent on digital travel content in the US

TOTAL US INTERNET MINUTES GREW BY 7%

>36% are seeking health advice before they leave1

70MAmericans Travelling Abroad

46MVisit Developing

Countries

Prioritytargets

1 – “Travel Health, Knowledge, Attitudes and Practices among United States Travelers.” J Travel Med 2004; 11:23–26.

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TRAVE LERS’ D I A R R H EA IS A HUGE HUGE HUGE M A R K ET


FACT 1: There are 46 million Americans traveling to high risk areas each year

FACT 2: Over a third of those Travelers are seeking health advice prior to leaving and paying out of pocket for OTC products and Traveler vaccines prior to their departure

FACT 3: The ISTM recommends traveling with an antibiotic for self-treatment when visiting developing regions1

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1. Riddle, M, et al. Guidelines for the prevention and treatment of travelers’ diarrhea: a graded expert panel report. Journal of Travel Medicine, Vol. 24(1):S63-S80, 2017.



TRAVELERS’ D I A R R H EA SH OU LD B E TA K EN SER IOU SLY

Bacterial Travelers’ diarrheapresents with a sudden onset of symptoms and usually lasts 3 to 7 days if untreated1

In some cases, symptoms can persist upon return2

• 1% have symptoms for ≥1 month• 17% continue to have symptoms upon

return• 2% have symptom onset only during

follow-up at home

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Infectious diarrhea can lead to lasting complications• Post-infection sequelae most often

include functional bowel disorders with persistent symptoms, such as post-infectious irritable bowel syndrome (PI-IBS)3

• Occurs in up to 10% of patients and may last for years even in the absence of infection1,4

1. Connor, B, Travelers’ Diarrhea. CDC Website, 2017. https://wwwnc.cdc.gov/travel/yellowbook/2018/the-pre-travel-consultation/travelers-diarrhea. Accessed Dec 9, 2018. 2. Steffen, R, Epidemiology of travellers’ diarrhea. Journal of Travel Medicine, Vol 24, Suppl 1, S2–S5, 2017. 3. Steffen, R, et al. Traveler’s Diarrhea: A Clinical Review. JAMA, Vol. 313(1):71-80, 2015 .4. DuPont, HL, Acute Infectious Diarrhea in Immunocompetent Adults, N Engl J Med, Vol.

370:1532-1540, 2014; .


Antibiotic therapy for the treatment of Travelers’ diarrhea is strongly supported and endorsed by multiple society guidelines to significantly shorten its duration and alleviate the associated disability1-3

The CDC and ISTM guidelines further suggest that earlyantibiotic treatment for moderate to severe Travelers’ diarrhea may help avoid disease severity, as well as possibly reducing the risk of post-infectious consequences2,4

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TRAVELERS SHOULD HAVE THE R IGHT ANT IB IOT IC IN THE IR POCKET IF TRAVELERS’ D I A R R H EA OCCURS

antibiotic go against the bacteria other drugs go against the symptoms

International Society of Travel Medicine (ISTM) in collaboration with the CDC2

American College of Gastroenterology (ACG)1

1. Riddle, M, et al. ACG Clinical Guideline: Diagnosis, Treatment, and Prevention of Acute Diarrheal Infections in Adults, American Journal of Gastroenterology, Vol. 111:602–622, 2016. 2. Riddle, M, et al. Guidelines for the prevention and treatment of travelers’ diarrhea: a graded expert panel report. Journal of Travel Medicine, Vol. 24(1):S63-S80, 2017. 3. Connor, B, Travelers’ Diarrhea. CDC Website, 2017. https://wwwnc.cdc.gov/travel/yellowbook/2018/the-pre-travel-consultation/travelers-diarrhea. Accessed Dec 9, 2018. 4. Riddle MS, Conner BA. Centers for Disease Control and Prevention. Perspective: antibiotics in travelers’ diarrhea—balancing the risks and benefits. https://wwwnc.cdc.gov/travel/yellowbook/2018/the-pre-travel-consultation/perspectives-antibiotics-in-travelers-diarrhea--balancing-the-risks-and-benefits, Accessed Dec 9, 2018.

https://wwwnc.cdc.gov/travel/yellowbook/2018/the-pre-travel-consultation/travelers-diarrhea

https://wwwnc.cdc.gov/travel/yellowbook/2018/the-pre-travel-consultation/perspectives-antibiotics-in-travelers-diarrhea--balancing-the-risks-and-benefits


Travelers’ Diarrhea can destroy your business trip or leisure holiday

Travelers’ Diarrhea can keep you on the toilet for a week

Aemcolo can heal you in 24 hours

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Cosmo Pharmaceuticals Presentation title goes here46

We are not selling treatmentWe are selling “insurance”


A EM C O L O B U SI N ESS M O D EL W I T H U S T R AVEL ER S

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TelemedicineProvider

AEMCOLO WEBSITE

THE BUSINESS MODEL TAPS INTO KEY POINTS OF INFLUENCE, AND LEVERAGES NEW TECHNOLOGIES/BUSINESS MODELS TO PROVIDE EASIER ACCESS TO TRAVELERS

Link to telemedicine provider

CONDITION, PRODUCT AND PRESCRIBING INFORMATION

Online DTC MARKETING Limited HCP

Online consultation

with HCPe-Rx HOME DELIVERY

OF AEMCOLO

Increase Traveler awareness and perception of risk to drive traffic to the website


TRAVELERS’ D I A R R H EA : H OW TO C A PT U R E T H E OPPOR T U N IT YLEVE RAGE EXPERIENCE & BRING ON BOARD THE WELL KNOWN PLAYERS IN THE F IELD

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• Experienced marketing partner• Direct experience in Travelers’ health• Strong international team

Strong marketing partner

• End to end provider – telemedicine through to warehousing, pharmacy dispensing, and home delivery

Strong execution partner

Cosmo US commercial organization has direct experience in GI, consumer health/ marketing, digital marketing


TRENDS IN HEALTHCARE

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>95% of community pharmacies do e-prescribing


TRENDS IN HEALTHCARE

• According to the majority of healthcare players, the main purpose of the digital transformation iscustomer engagement

• 50% of companies over USD 100m sales expectto invest heavily in digital transformation in the next year

• 27% of healthcare industry executives state thattheir organization have already a formal digitaltransformation strategy ongoing

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Source: Global data


A EM C O L O B U SI N ESS M O D EL W I T H T R AVEL ER S: B EN EF I T S

• More straightforward sales and distribution• Remove need for large sales infrastructure• Reduce complexity for the wholesalers and distribution chain in Travelers’ diarrhea

• Marketing directly to the Traveler• KOLs are important stakeholders but limited direct detailing to broad HCP population required

• Will be able to use real time feedback from the value chain to help refine marketing campaigns, rebate programs, messaging etc.

• Expand promotion and messaging to physicians

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High travel spending per person in the US facilitates big commercial opportunity

https://www.aarp.org/content/dam/aarp/research/surveys_statistics/life-leisure/2017/2018-travel-trends.doi.10.26419-2Fres.00179.001.pdf

https://www.aarp.org/content/dam/aarp/research/surveys_statistics/life-leisure/2017/2018-travel-trends.doi.10.26419-2Fres.00179.001.pdf


NEW PRODUCTS IN THE PIPELINE

P R O F. M I C H E L E M A I O , D I R E C TO R O F I M M U N O- O N C O L O G Y C E N TE R , U N I V E R S I TY O F S I E N A

M A R A G E R L O N I , B E L L ATR I X P H A R M A C E U TI C A L S C S O

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In the last 10 years cancer treatment scenarios has completely changed

thanks to a significant improvement in scientific knowledge and availability of

predictive markers

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N EW A C T I VE SU B STA N C E A PPR O VA L S IN ONCOLOGY B Y IND ICAT ION , 2013 -2017

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Development time and time to markethas dramatically decreased and

most of the recent approved new active substances for cancer treatment

were introduced into the marketafter an approval based

on a single trial or phase II studies

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ONCOLOGIC N EW A C T I VES SU B STA N C ES (N A S) LAUNCHED FOR THE F IRST T IME IN U N I T ED STATES IN 2017

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NOT ONLY BIG PHARMA…

Clinical development of new oncology drugs is generally started by small biotech and partnered to big pharma upon proof of effectiveness in one

or more indications

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C O M PA N Y L AT E-STA GE P IPEL IN ES , N U M B ER OF ONCOLOGY INDICAT IONS A N D ONCOLOGY PER C EN TA GE OF P IPEL INE

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NOT ONLY BIOLOGICS…

In the last 10 years the number of biologic drugsin late stage of development tripled, but small

molecules increased as well; on the contrary the number of cytotoxic drugs significantly decreased

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THE P IPEL INE OF LATE PH A SE ONCOLOGY M OL EC U L ES , 2007 -2017

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Despite immunotherapy representingthe most important advancement in cancer

treatment, still very few patients are treated with this approach thus leaving a big opportunity

particularly in some selected tumor types

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PD- 1 A N D PD- L1 INH IB ITOR TREATED PAT IEN T S B Y TUMOR TYPEIN THE US

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C A N C ER OF U N M ET N EED

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4 EXA M PL ES OF U N M ET M ED IC A L N EED

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01 TRIPLE NEGATIVE BREAST CANCER

TNBC are negative for estrogen, progesteron and HER2 receptors. TNBC represent 15-25% of total breast cancers and typically responsive to chemotherapy. Depending on the stage of its diagnosis, triple negative breast cancer can be particularly aggressive, and more likely to recur than other subtypes of breast cancers

02 HORMONE REFRACTORY OR CASTRATION-RESISTANT PROSTATE CANCER (HRPC/CRPC):

HRPC/CRPC are no longer responsive to castration treatment. Life expectancy is months

03 STAGE IV COLORECTAL CANCER

Cancer that has metastasized to other parts of the body is usually not curable, with a 7% of survival at 5 years

04 PANCREATIC CANCER

Pancreatic cancer is the fourth most common cause of cancer-related deaths in the United States and the eighth worldwide. Pancreatic cancer has an extremely poor prognosis: for all stages combined, the 1- and 5-year relative survival rates are 25% and 6% respectively


SU M M A RY ON TRENDS

• Cancer Treatment Paradigm has completely shifted in the last 10 yrs

• Time to Market and approval process has significantly decreased

• Most of the innovative approaches come from small companies and then expanded by Big Pharma at later stage

• Almost half of the compounds under development belong to the “small molecules” category

• Despite the significant improvement in cancer treatment there is still a huge area of unmet medical need which represent a great opportunity for innovative approach

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C B -03 - 10 : PH A SE 1 R EA D Y A N D R OGEN R EC EPTOR A N TA GON IST FOR SOL ID TU M OR S

Several Cosmo Pharmaceuticals Compounds, derived from Cortexolone were screened as potential treatment for Diseases dependent on the Androgen receptor

For Acne Treatment (Winlevi)For Alopecia Treatment (Breezula)

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For Treatment of Solid tumors

CB-03-10 was selected from a Compound Library owned by Cosmo Pharmaceuticals

CB-03-01/Clascoterone

CB-03-10


C B -03 - 10 IS A POT EN T A N TA GON IST OF T H E A N D R OGEN R EC EPTOR W IT H A N T I -TUMOR ACT IV ITY

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In vivo treatment of human prostate cancer (LNCap) implanted in the mouse

Tissue Type Cell Line Name CB-03-10 Enza Gemcitabine

Paclitaxel

In Vitro Citoxicity IC50

Prostate CancerLNCaP 10 50

LNCaP EnzaR 13 123

Pancreatic CancerPanc1 38 125

MiaPac2 23 56 17

Breast CancerMCF7 82 146

TNBCMDA-MB-231 55 130 0.028

Colon Cancer HT29 14 150


C B -03 - 10 H A S B EEN A PPR OVED B Y T H E F D A F OR A PH A SE 1 C L IN IC A L T R IA L IN CANCER PAT IENTS

• Mechanism of Action is via high potency antagonism of both Androgen and Glucocorticoid Receptors

• Potent in vitro and in vivo anti-tumor activity across many different cancers• Pancreatic, Colon, Prostate

• More potent than Enzalutamide - the current treatment for prostate cancer• High activity in enzalutamide-resistant tumors; suggested as second line therapy

• GR inhibition may also potentially increase sensitivity to chemotherapy in cancer therapy and could compensate the lack of activity after some time of exposure recorded for other cell receptors

• Regulatory Toxicology findings confirm that oral administration is safe

• Very high therapeutic window (against normal cells) with less side effects when administered in patients

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C B -03 - 10 PH A SE 1 M U LT IC EN T ER T R IA L

Part 1 Dose escalation: Up to 27 patients

Subjects with advanced refractory tumors

Part 2 Dose expansion: Up to 63 patients

Defined subject sub-groups showing meaningful clinical activity in Part 1

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C B -03 - 10 PL A N TO L IC EN SE F OL L OW IN G PH A SE 1 C L IN IC A L T R IA L

• High interest in therapies for solid tumors • Solid tumors, specifically pancreatic, with high unmet medical need can be targeted. Pancreatic tumor

five-year survival rates remain low in the US at 8.5%.• Colorectal cancer is the 2nd leading cause of cancer death among men and women combined in the

United States. There will be an estimated 140,250 new cases of colorectal cancer in 2019

• Multiple licensing partners have shown interest in the compound because • Clinical trials for pancreatic cancer are granted Orphan Drug Designation and accelerated approval• 15% – 30% of Prostate cancer patients don’t respond to Abiraterone or Enzalutamide as first line therapy,

CB-03-10 would work on these patients that become resistant to those therapies

• CB-03-10 is of high interest to Big Pharma as a licensing candidate because of its potential for first and second line therapy in solid tumors. Among those are pancreatic cancer, colon cancer and certain subtypes of prostate cancer that share a poor prognosis and a high un-met therapeutic need

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CB-03-10 is a highly potent AR and GR antagonist with impressive anti-tumor activity

Potential for first and second line therapy in Pancreatic, Colon and other cancers

Regulatory Toxicology shows oral dosing is Safe and Well-Tolerated

IND approved without revision by the FDA

Phase 1 Clinical trial scheduled to begin 4Q 2019

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SU M M A RY

R&D Day 2019

Potential licensing partners looking to execute a deal


OUTLOOKA L E S S A N D R O D E L L A C H À , C E O

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OUTLOOK

A consistent diversified pipeline in different stages of developmentFour products already in the marketOne new product ready to enter the market

Net cash of € 348m at May 6, 2019

Convertible financing raised to build up commercial infrastructure and scale up of AI business: now not necessary after deal with Medtronic, increases firepower

Ready to capture additional opportunities

R&D Day 201974


THANK YOU

Presentation title goes here75


Cosmo Pharmaceuticals NVRiverside IISir John Rogerson’s Quay Dublin 2, [email protected]

Mr. Alessandro Della Cha , [email protected]

Mr. John Manieri, [email protected]+353 1 817 03 70

mailto:[email protected]



Cosmo Pharmaceuticals NVRiverside IISir John Rogerson’s Quay Dublin 2, [email protected]

Mr. Alessandro Della Cha , [email protected]

Mr. John Manieri, [email protected]+353 1 817 03 70




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