drug delivery recent technology trends and solutionsbut this is a highly specialized and very...

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Drug Delivery

Recent Technology Trends

and Solutions

Dr. Stefan Bracht

Head of Disruptive Technologies

Chemical & Pharmaceutical Development

March 11-13th - 2019

Agenda

New drugs & generics on the

2017/2018 market

Current focus areas & examples at

Bayer, Pharmaceuticals

What is going to come next ? - Outlook

2 Stefan Bracht – Bayer AG at 10th Global Drug Delivery & Formulation Summit, Berlin, March 11-13th, 2019

3

What’s new?

https://www.fda.gov/downloads/Drugs/DevelopmentApprovalProcess/DrugInnovation/UCM629290.pdf

Stefan Bracht – Bayer AG at 10th Global Drug Delivery & Formulation Summit, Berlin, March 11-13th, 2019

What’s new?

Stefan Bracht – Bayer AG at 8th Annual Drug Delivery & Formulation Summit-Asia – Shanghai – Oct 25&26, 2018

Nature Reviews | Drug Discovery volume 18 | FEBRUARY 2019 | 87

What’s new?


Drug Delivery, Featured Articles, Formulation Development - March 2019

GLOBAL REPORT – 2018 Global Drug Delivery & Formulation Report: Part 1, a Global Review

By: Kurt Sedo, VP of Operations, and Tugrul Kararli, PhD, President & Founder, PharmaCircle

https://drug-dev.com/global-report-2018-global-drug-delivery-formulation-report-part-1-

a-global-review/

https://drug-dev.com/category/drug-delivery-technologies/

https://drug-dev.com/category/featured-articles/

https://drug-dev.com/category/formulation-development/

https://drug-dev.com/issues/march-2019/

Polymer Based Drug Delivery

What’s new?

First peripheral vascular interventional technology approved in the U.S. to

offer sustained release of antiproliferative drug to treat patients with

peripheral artery disease

Sep 24, 2018

https://www.cardiovascularbusiness.com/topics/vascular-endovascular/eluvia-vascular-stent-fda-approval

https://www.americanpharmaceuticalreview.com/Specialty/Drug_Delivery/1315-News/


https://www.arikayce.com/pdf/ARIKAYCE_Quick_Start_Guide.pdf

FDA News Release

FDA approves a new antibacterial drug to treat a

serious lung disease using a novel pathway to

spur innovation Sept 18, 2018

Phase III study with Amikacin Inhale in intubated

and mechanically ventilated patients with Gram-

negative pneumonia does not meet primary

endpoint of superiority WHIPPANY, N.J., Nov. 24, 2017 /PRNewswire/

What’s new in the Generics Arena? I/II

https://www.deutsche-apotheker-zeitung.de/news/artikel/2017/08/14/verhuetungsringe-jetzt-auch-

ungekuehlt

Generics can be stored at room temp

Cyclelle®, Ginoring®, Setlona® und Veri-Aristo®,

Originator

NuvaRing®

(contraceptive vaginal ring)

Needs refrigerated supply chain


Bioequivalence based on delivered dose in inhalation

Jaime Algorta et al.: Pharmacokinetic Bioequivalence of Two Inhaled Tiotropium Bromide Formulations in Healthy Volunteers, Clin

Drug Investig. 2016; 36(9): 753–762.

Pharmacokinetic Bioequivalence of Two Inhaled Tiotropium

Bromide Formulations in Healthy Volunteersallowing a less active tiotropium metered dose

(13 µg/capsule) while maintaining the same delivered dose

(10 µg/actuation)

https://www.apotheke-

adhoc.de/nachrichten/detail/pharmazie/braltusspiriva-

warum-13-dasselbe-wie-18-ist/

What’s new in the Generics Arena? II/II


What’s new about “Chip on a Pill”?

https://thasso.com/abilify-mycite-the-first-digital-pill-where-does-all-that-silicon-go/


ATMP / CGT

What’s new?

www.ema.europa.eu/documents/annual-report/2017 (published May 2018)

The criteria for ATMPs are set out in Article 17 of Regulation (EC) No 1394/2007.

The classification procedure is optional.

FDA: Chemistry, Manufacturing, and Control (CMC) Information for Human Gene Therapy

Investigational New Drug Applications (INDs) Draft Guidance for Industry – July 2018


http://www.ema.europa.eu/documents/annual-report/2017

http://ec.europa.eu/health/files/eudralex/vol-1/reg_2007_1394/reg_2007_1394_en.pdf

What’s new?

EMA Approval: 08/2018

EMA Approval: 08/2018


autologous use only

for autologous use only

13

Current drug delivery

focus areas & examples at Bayer, Pharmaceuticals


Placeholder

extended treatment duration

improved convenience

improved PK/PD relationship

better targeting / drug delivery

disease control by patient

special patient groups

Patient centricity – addressing the unmet patient need

Innovation for patients in drug delivery


Mini tablets for Children (and the Elderly?)

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Application systems for 1-20 mini tablets - Commercially not available


e.g. Pegylated Proteins

What’s new?

Through its site- specific PEGylation, Jivi has a half-life of 17.9 hours that

delivers sustained levels in the blood*

*Jivi® [prescribing information]. Whippany, NJ: Bayer; 2018.


Still highly wanted back of the eye depot formulations…What’s new?

Eylea; August 17, 2018

Via sBLA FDA approves Eylea 12-week

dosing for wet AMD

…the current challenge is to

devise a longer-lasting and

minimally invasive mode of

administration for protein drugs.

In this regard, although research

activity is intense, no system

has advanced beyond the

preclinical stage.

K Radhakrishnan et al.: Protein delivery to the back

of the eye: barriers, carriers and stability of anti-

VEGF proteins in Drug Discovery Today Volume 22,

Number 2 February 2017:


https://www.research.bayer.com/en/fighting-cancer-with-radio-immunotherapy.aspx

Bayer´s next step into targeted alpha-radiotherapies


Radiotherapies – targeted beta-emitters

Advanced Accelerator

Applications Announces

(AAA) Completion of

$3.9 Billion Novartis

Tender Offer Novartis

Global Oncology

Expertise to Enhance

Launch of Lutetium Lu

177 Dotatate

(LUTATHERA®) and

Accelerate Development

of Theragnostic Pipeline.

https://www.adacap.com/flash-news/2018/

https://www.genengnews.com/news/novartis-to-acquire-endocyte-for-2-1b-expanding-rlt-

pipeline-in-prostate-cancer/


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What is going to come next ? - Outlook


Oral protein/peptides

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Currently 2 products in late stage (on top of 2 registred products like Minirin® Tablets):

Tbria (calcitonin, 32 amino acids) and Mycapssa (octrotide, 8 amino acids)


„Roboter Pill“ keeps moving ahead

https://interestingengineering.com/robotic-pills-to-remove-injections-for-diabetes


o Application depends on contact with gut surface; gut

mucosa is covered with a film of mucus, which might

impact „injection“

o Diameter of the small intestine still is 1 inch (2.54 cm)

equivalant to Capsule size 00 or 000

o Same hurdles like for long time existing „mucoadhesive“

systems,

o Injection in the gut mucosa might generate holes for other

substances as well, which should not penetrate the

mucosa (toxins, or other drugs) Price/ applicable Dose

o → Might rather be an option for very high potency drugs

with wide therapeutic window

Challenges from an expert point of view :Standard Capsule sizes

Oral delivery of proteins is the holy grail of drug delivery

Improved convenience


/// Bayer 16:9 Template /// September 201824

New Therapeutic Modalities


E. Valeur et al., New Modalities for challenging targets in Drug Discovery, Angew. Chem. 2017

Eric Valeur*:

Indeed, from a

therapeutic modality

point-of-view, the

pharmaceutical industry

has a heavily silo-biased

structure. A stereotype is

to consider on one hand

small molecules and on

the other hand biologics.

What might come next ?: New Modalities ?

*Associate Director, New Modalities,

Cardiovascular and Metabolic Diseases,

Innovative Medicines and Early Development

Biotech Unit, AstraZeneca, UK


Cargo Local Delivery

i.v. targetedRNA

Cas9

DNA

Viral and non viral delivery systems are a

group of technologies that aim to deliver gene-

editing therapy in-vivo to target organs.

Delivery Technology

VIRAL and NON-VIRAL

Targeted Delivery

What might come next ?: e.g. Gene Editing ?


GBI Research Analysis (2018)

Number of licensing deals by vector

ATMPs – viral vectors

/// Bayer 16:9 Template /// September 201829

Data as an Asset


Predicting oral disintegration time

AI in Formulation Development: Quality Output depends on Quality Input !

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Han et al., Asian J Pharm Sci (2018) in press


Predicting oral disintegrtion time

AI in Formulation Development

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Formulation

Han et al., Asian J Pharm Sci (2018) in press

Testing set: 80 % accuracy


Summary

o The pharmaceutical industry has delivered significant therapeutic innovation during the past 2 years –

but this is a highly specialized and very diverse portfolio of sometimes niche products

o Drug Delivery remains a key factor in pharmaceutical innovation, driven by patient needs and new

treatment modalities – also reflected in Generics that further address patient needs

o Personalized and individualized approaches will be of increasing importance in future drug delivery

e.g. in allogenic and even more so in autologous cell therapies.

o Gene-editing holds the potential to be disruptive in a number of – mostly monogenetic diseases.

In the next decade this fast-growing area will require new DD-strategies to enable optimal targeting.

o Still high need for advanced parenteral targeting – also in times of limited ADC successes

Footnote: Where will the medical use of Cannabis and Marihuana be heading at ?

(THC, CBD and other Cannabinoids)


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Thank you!

Bye-Bye


Forward-Looking Statements

This presentation may contain forward-looking statements based on current assumptions and forecasts

made by Bayer management.

Various known and unknown risks, uncertainties and other factors could lead to material differences

between the actual future results, financial situation, development or performance of the company and the

estimates given here. These factors include those discussed in Bayer’s public reports which are available

on the Bayer website at http://www.bayer.com/.

The company assumes no liability whatsoever to update these forward-looking statements or to conform

them to future events or developments.


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