After Inflammation, Fibrosis – is it Time to Follow Nature ... · PDF fileAfter Inflammation, Fibrosis – is it Time to Follow ... and fungal infections AND the pathogenesis of

1 BES 2016 AIID/Fibrosis Panel © Defined Health, 2016

After Inflammation, Fibrosis – is it Time to Follow Nature's Lead?

Moderator: David J. Lomb, PhD – Senior Consultant, Defined Health Panelists: Donnie McGrath, MD, MPH – VP, Search and Evaluation, BMS Elias Papatheodorou – CEO, Genkyotex S.A Hans T. Schambye, MD, PhD – CEO, Galecto Biotech AB Matthias Corbascio, MD, PhD – VP, IsletOne Therapeutics


The information in this presentation has been obtained from what are believed to be reliable sources and has been verified whenever possible. Nevertheless, we cannot guarantee the information contained herein as to accuracy or completeness. All expressions of opinion are the responsibility of Defined Health, and though current as of the date of this report, are subject to change. The opinions and information set forth herein are expressed solely for the benefit of the addressee and only for the purpose(s) for which the report was produced. Without the prior written consent of Defined Health, this report may not be relied on in whole or in part for any other purpose or by any other person or entity, provided that this report may be disclosed where disclosure is required by law. This report may contain information provided by third parties such as Thomson Reuters, Springer, EvaluatePharma, Datamonitor, Informa Healthcare, IMS Health and others with a proprietary interest in the data provided herein. Please note that you are not permitted to redistribute any such third party information without consent from the originator company. © Defined Health, 2016


The Autoimmune Inflammatory Disease (AIID) Category is One of the Largest in the Pharmaceutical Industry Responsible for ~$50B/Year

EvaluatePharma

$0 $5,000 $10,000 $15,000 $20,000 $25,000

Sjögren's syndrome

Systemic lupus erythematosus (SLE)

Ankylosing spondylitis

Psoriatic arthritis

Ulcerative Cholitis

Crohn's Disease

Psoriasis

Rheumatoid Arthritis

USD mln

Top AIID Indication 2015 WW Sales

US

ROW


Success in the AIID Category has been Driven by Development of Therapeutics Targeting Conserved Mediators of AIID Diseases (e.g. TNFα)

♦ TNF-α is a potent inducer of the inflammatory response, a key regulator of innate immunity and plays an important role in the regulation of Th1 immune responses against intracellular bacteria and certain viral infections.

♦ However, dysregulated TNF can also contribute to numerous immune-mediated inflammatory diseases including rheumatoid arthritis, Crohn's disease, psoriatic arthritis, ankylosing spondylitis, ulcerative colitis and severe chronic plaque psoriasis.

Immunotherapy. 2010 Nov;2(6):817-33. doi: 10.2217/imt.10.67.

http://www.ncbi.nlm.nih.gov/pubmed/?term=Immunotherapy.+2010;2(6):817-833�


Success in the AIID Category has been Driven by Development of Therapeutics Targeting Conserved Mediators of AIID Diseases (e.g. TNFα)

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Enbrel

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Evaluate Pharma; Adis Insight; DH Analysis

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Humira M P3 - M M M M - - M M M M M P3 DIS - - -

Simponi P3 DIS - M - M M - - - - M - - - - P1/2 - -

Remicade - - REG M M M M - - M - M M - - - - M -

Cimzia P3 - - M P3 M M - - - - - M - - P3 - - M

*Highlighted is First to Market


Success in the AIID Category Continues to be Driven by Development of Therapeutics Targeting Conserved Mediators of AIID Diseases (e.g. IL-17)

♦ IL-17 is a hallmark cytokine of Th17 cells that plays critical roles in host defense against bacterial and fungal infections AND the pathogenesis of multiple autoimmune diseases (e.g. rheumatoid arthritis, asthma, lupus, allograft rejection, anti-tumor immunity, psoriasis, multiple sclerosis).

♦ Antibodies targeting IL-17A (i.e. Novartis’s Cosentyx/secukinumab and Lilly’s ixekizumab) have already been approved for psoriasis and these agents and others targeting the IL-17 pathway (e.g. Valeant’s brodalumab) are being investigated for a wide variety of additional AIID indications.

Dermatol Ther. 2015 Jul-Aug;28(4):179-93; Nat Rev Drug Discov. 2012 Oct;11(10):763-76

http://www.ncbi.nlm.nih.gov/pubmed/?term=Nature+Reviews+Drug+Discovery+11,+763-776�


Success in the AIID Category Continues to be Driven by Development of Therapeutics Targeting Conserved Mediators of AIID Diseases (e.g. IL-17)

AdisInsight; Cortelis; EvaluatePharma

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Ixekizumab PREG - P3 P2 - - - - -

Secukinumab M - M P3 REG P3 P3 P2 P2

Brodalumab PREG PREG P3 DIS - PREG DIS - -


Although Pharma Continues to Profit from AIID, Innovators May Soon Need to Look Elsewhere

Evaluate Pharma; DH Analysis; http://pi.amgen.com/united_states/enbrel/derm/enbrel_pi.pdf; http://www.rxabbvie.com/pdf/humira.pdf

Rheumatoid Arthritis Psoriasis Inflammatory Bowel Disease

♦ Key indications driving sales in the AIID category are well-served by available products.



♦ Existing franchises now cover many of the remaining AIID indications.

Adis Insight; Thomas Reuters Cortellis

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♦ Payers are pushing back on products that don’t provide superior outcomes compared to currently available therapies.

EvaluatePharma; lookup.decisionresourcesgroup.com/

Aetna Premier 5-Tier Open

Anthem (BC California)

BCBS Texas Cigna Legacy 3-Tier

UnitedHealthcare Advantage

Cosentyx Tier 5 specialty, PA, ST Tier 3 non-preferred, PA, QL Tier 3 specialty, QL, ST Tier 3 non-preferred,

PA Tier 3 non-preferred,

PA, QL, ST

Otezla Tier 5 specialty, PA,

QL, ST Tier 3 non-preferred,

PA, QL Tier 3 specialty, QL, ST Tier 3 non-preferred, PA

Tier 3 non-preferred, PA, QL, ST

Xeljanz Tier 5 specialty, PA,

QL, ST Tier 3 non-preferred,

PA, QL Tier 3 specialty, QL, ST Tier 3 non-preferred, PA

Tier 3 non-preferred, PA, QL, ST

Xeljanz – although Xeljanz received a label permitting use ahead of anti-TNFs, physician hesitance and payor policies tend to restrict Xeljanz’s initial use to TNF-failure patients.



♦ The biosimilars are coming!

www.pharmexec.com/pharm-execs-2016-pipeline-report


Like AIID, Fibrosis Represents a Common Process Driven by Conserved Mediators (e.g. TGF-β, PDGF, oxidative stress, galectins)

Physiol Rev. 2008 Jan;88(1):125-72

http://www.ncbi.nlm.nih.gov/pubmed/?term=Hepatic+Stellate+Cells:+Protean,+Multifunctional,+and+Enigmatic+Cells+of+the+Liver�




However, Fibrosis Remains an Area of Great Unmet Need and Largely Untapped Commercial Potential

♦ Nearly 50% of all deaths in the developed world are associated with some type of chronic fibroproliferative disease.

♦ Fibrosis alters the architecture of organs and tissues, thereby disrupting normal function.

♦ Fibrosis can affect almost any organ or tissue and is associated with a wide variety of diseases and injuries.

♦ So far, only two products have been approved for a “fibrosis” indication (i.e. Roche’s Pirfenidone and BI’s Ofev, both approved for IPF).

♦ However, there has been intense interest in NASH over the last few years and a number of drugs are now approaching the finish line (e.g. Intercept’s obeticholic acid, Genfit’s GFT-505).

www.promedior.com; J Clin Invest. 2007 Mar;117(3):524-9; IPF = idiopathic pulmonary fibrosis

With an estimated 16-30 million adults affected in the U.S. alone and no FDA approved treatments, non-alcoholic steatohepatitis (NASH) has been proclaimed “the Next Big Global Epidemic” and “the Next Hepatitis C.” Indeed, analysts now forecast that the market for NASH treatments could reach $35-40 Billion by 2025.

http://www.promedior.com/�


Accordingly, Anti-Fibrotic Assets and Companies Have Become Very Attractive to Pharma Dealmakers and Investors Alike

Fiercebiotech


However, Fibrosis Poses its Own Unique Set of Challenges and Important Questions Remain to be Answered

♦ Which primary endpoint(s) are regulatory agencies most likely to accept for regulatory approval of anti-fibrotic drugs?

♦ What will a label indication for an anti-fibrotic drug look like?

♦ How will clinicians determine which patients to treat with an anti-fibrotic drug?

♦ When will non-invasive tools for diagnosing fibrosis and monitoring response to treatment become more widely used in the clinic?

♦ What criteria will payers use to determine patient eligibility for treatment with anti-fibrotic drugs?

♦ What issues/barriers/obstacles remain to developing anti-fibrotic drugs?


This Panel will Discuss the Potential and Pitfalls of Looking Beyond AIID to the Unchartered Territory of Fibrosis

♦ Do significant opportunities remain for small biotechs looking to innovate in the AIID space, and if so, which opportunities offer the greatest potential for partnering with Pharma?

♦ If it is time to start looking beyond AIID, is fibrosis the best space in which to play? ♦ Given that fibrosis is often the end result of inflammation, how well-positioned are

AIID-focused biotech companies to move into this space? ♦ Which fibrosis indications is Pharma currently most interested in and why, and

which of these, if any, are AIID-focused biotechs best positioned to tackle?

♦ What are the most important issues/barriers/obstacles that remain to developing anti-fibrotic drugs?


David J. Lomb, PhD, Senior Consultant, Defined Health

♦ As a Senior Consultant with Defined Health, David participates in and leads opportunity assessments as well as indication prioritization/sequencing, search, and strategy projects. David regularly contributes to projects in the oncology, dermatology, CNS, and autoimmune and inflammatory disease spaces. In addition, David leads most projects involving the fibrosis therapeutic area at Defined Health.

♦ Prior to joining Defined Health in 2010, David was a postdoctoral fellow in the Paul F. Glenn Laboratories for the Biological Mechanisms of Aging at Harvard Medical School. As a scientist at Harvard, David studied a family of enzymes known as sirtuins which have been implicated in the regulation of aging and age-related diseases. Also while at Harvard, David was a fellow in the Early Technology Assessment Program sponsored by the Office of Technology Development. In this position, David was responsible for performing initial commercial assessments of discoveries made by Harvard faculty members.

♦ David earned a PhD in Pharmacology from the University of Rochester, in Rochester, New York, where his thesis work focused on the molecular mechanisms of neuronal programmed cell death. David has also earned Bachelor of Science degrees in both Biochemical Pharmacology and Psychology from the University at Buffalo, in Buffalo, New York. David has published in peer reviewed scientific journals and has presented his work at national scientific meetings.


Defined Health is Pleased to Present:

Defined Health will be participating in the following events:

Therapeutic Insight by Defined Health at BioEurope Spring | April 4 - 6, 2016 Stockholm, Sweden | http://www.therapeuticinsight.com

AACR Annual Meeting 2016 | April 16 - 20, 2016 New Orleans, LA | http://dfndhlth.com/AACR-2016 ASGCT | May 4 - 7, 2016 Washington, DC | http://dfndhlth.com/ASGCT-2016 ASCO | May 29 - June 2, 2016 Chicago IL | http://dfndhlth.com/ASCO-2016

BIO International Convention | June 6 - 9, 2016 San Francisco, CA | http://dfndhlth.com/BIO-2016 Pharma CI USA Conference | September 13 - 14, 2016 Parsippany, NJ | http://dfndhlth.com/PharmaCIUSA

The International Cancer Immunotherapy Conference | September 25 - 28, 2016 New York City | http://dfndhlth.com/ICIC-2016 LES Annual Conference | October 23 - 2 6, 2016 Vancouver, BC | http://dfndhlth.com/LES-2016 Bio-Europe | November 7 – 9, 2016 Cologne, Germany | http://dfndhlth.com/Bio-Europe2016

SITC 2016 | November 9 – 13, 2016 National Harbor, MD | http://dfndhlth.com/SITC-2016 ASH Annual Meeting | December 3 - 6, 2016 San Diego, CA | http://dfndhlth.com/ASH-2016

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After Inflammation, Fibrosis – is it Time to Follow Nature ... · PDF fileAfter Inflammation, Fibrosis – is it Time to Follow ... and fungal infections AND the pathogenesis of