Entrepreneurship 101 - Science and Entrepreneurship 101 - Science and Business do MixBusiness do Mix

Mathieu Boudreau

MaRS Lecture Series

March 13, 2007

From Research to Business Development & From Research to Business Development & Licensing – When Science and Business Licensing – When Science and Business

Make a Perfect Blend Make a Perfect Blend

PrefacePreface The objective of this presentation is to share my experience

(good & bad) as it relates to my transition from academic science to business:

• Transitioning from the “bench” to a biotech business development/licensing career via an “unexpected & unplanned” entrepreneurship experience!

Notice: statements and conclusions in this presentation reflect personal experience - are subjective, and may not apply to everyone.

This presentation contains subject matter which may This presentation contains subject matter which may cause extreme pleasure and uncontrollable urges to cause extreme pleasure and uncontrollable urges to become an entrepreneur – VIEWER DISCRETION IS become an entrepreneur – VIEWER DISCRETION IS ADVISED!ADVISED!

OutlineOutline Background on Doctoral Studies How it All Started Starting-Up a Business The Rise and Fall of a Start-Up What Would I Do Differently? What Did I Learn from This? Choosing a New Career Path About Aegera Therapeutics Inc. What’s my Job Like? What’s Next?

Background on Doctoral StudiesBackground on Doctoral Studies

Ph.D. at McGill – Montreal Neurological Institute Supervisor: Dr. David R. Kaplan Thesis: The roles of Akt in the regulation of

apoptosis/survival of neurons and glioblastoma cells

• Negative regulation of MLK-3/JNK by Akt-dependent phosphorylation

• Positive regulation of XIAP by Akt-dependent phosphorylation

General interests: signalling complex/scaffold dynamics

How it All StartedHow it All Started Met a group of physicists/software engineers in a coffee

shop in 2000

• They a had developed prototype technologies for medical imaging/computer-assisted detection (CAD).

• Were interested in starting-up a company to develop the prototypes for medical applications in vascular diseases.

• Needed someone who could “speak the language” and may have contacts in the medical field.

Subsequently became involved on a part-time basis (evenings and weekends) while I was still in grad school

• Establishing contacts for Research collaborations• Writing Business Plan

Step 1 – Writing a business plan (2001)

Learned how to write a business plan

• Researched market and competitive environment data and established a marketing/sales plan

Recipient of several business plan/entrepreneurship competition awards - including cash bursaries

• As a result became incubated by the HEC-poly-University of Montreal Entrepreneurship Center

• The Company hired its first part time employee

How it All StartedHow it All Started

Step 2 – Seeking seed financing (2001/2002)

Raised close to $2 million in seed financing (debt and grants)

• Built a small team• Nominated an Advisory Committee• Developed a solid scientific/business/legal

“entourage”• Filed patent applications• Setup research collaborations (academic and

industrial)• Developed products to proof of concept/beta testing

How it All StartedHow it All Started

Facing ChoicesFacing Choices As I was finishing up my Ph.D. I needed to make a decision

as it relates to my career path.......

The Rise....The Rise.... Built a team of up to 17 people Signed several collaboration agreements (research & business) Signed a contract (product sale/custom development) with a mid-

cap biotech company Identified important business opportunity In-licensed patent portfolio and prototype for a medical device from

a small biotech company• Fiber optic sensor-based diagnostic/interventional catheter for

vulnerable atherosclerotic plaque• To be coupled to our other products in development

Engaged in advanced discussions with several medical device and pharmaceutical companies around our company and products

Engaged in advanced negotiations with a medical device company interested in acquiring our company

And then........

.... And Fall of a Start-up.... And Fall of a Start-up Companies ended up not agreeing on the terms of the acquisition Our Company did not have much cash flow

Our normal operations/product development were significantly slowed down by the M&A discussions

• Due diligence process impeded our normal activities and delayed our planned product development timelines

We were having a difficult time attracting VC investment – early products, high risk/competition

In an effort to reduce expenditures and allow the Company time to select the best strategic option, we implemented a restructuring plan which involved downsizing

However, in spite of significant efforts to turn the situation around the Company was forced to cease its operations

The rest became an exercise in “damage control”

What Would I do Differently?What Would I do Differently?

I would join an experienced/senior team from which I would learn more efficiently – Great value in learning from experienced individuals – less learning from our own or other people’s mistakes

Would probably become involved in a project with more mature products/technologies

Would favor a more pragmatic and focused approach • Initially build on one project

Would probably become involved in a drug discovery/development company

What Did I Learn From This?What Did I Learn From This? Having a good relationship with my supervisor was key –

Dr. Kaplan was very supportive of my involvement in this company, even as a graduate student

Making career choices out of frustration is not ideal

Being bold, taking chances, trying new things is a good thing – but staying rational and understanding your level of tolerance to risk and stress is very important!

Make sure that you get along with your future colleagues/partners – you spend a lot of time with them when you start-up a company

Learn how to set your limits both physically and emotionally

What Did I Learn From This?What Did I Learn From This?

Make sure you understand or are advised on legal aspects – understand your personal liabilities

Give it all you’ve got – but being able to say that’s not what I want anymore is really important

Don’t let the prospects of financial success become your main driver/motivation!

Great scientific/technological ideas do not guarantee and are often not good enough for commercial success!

No regrets – anyways you can’t do anything about it!

Be open-minded to new opportunities Be open-minded to new opportunities

Aegera Therapeutics Inc.Aegera Therapeutics Inc.

Aegera Programs

• Apoptosis Inhibition for Cancer

Molecular Target: Inhibitor of Apoptosis Proteins (IAPs)

• AEG35156 Antisense Program

• IAP Small Molecule Program

• Apoptosis Inhibition for Neuropathy & Neuropathic Pain

Molecular Target: HSP 90/JNK Pathway Inhibition

• Small Molecule Program

Aegera’s FocusApoptosis Control Drugs

CancerCancerNeuropathyNeuropathy

&&

PainPain

• Diabetic

• Chemotherapeutic

• Autoimmune

• Inflammation

PreventFacilitate

APOPTOSI

S

Pipeline Status/Projections• Oncology

– AEG35156

• 2nd generation antisense in 4 Phase1-2 clinical trials

• Early indications of target knockdown/efficacy

• Multiple Phase 2 programs to be initiated in 2007

– Small Molecule IAP Inhibitor

• Solid in vitro/in vivo Proof-of-Principle

• Clinical development candidate selected in Q1/07

• Targeting i.v. P1 trial for Q1/08

• Neuropathy & Neuropathic Pain• Small molecule program that targets HSP90/JNK Pathway

• Strong in vitro/in vivo for diabetic neuropathic pain

• Targeting oral P1 trial for Q4/07

TARGETED APOPTOSIS CONTROLTARGETED APOPTOSIS CONTROL

AEGERAAEGERAR&D STRATEGYR&D STRATEGY

Dominant Intellectual Property Base – Over 100 Issued & Pending Patents/Applications• Five Members of the IAP Family (Antibodies, Genes & Fragments) • Composition of Matter/Pharmaceutical Compositions – Antisense, Small Molecules• Methods of Treatment – Cancer, Neuropathic Pain/Neuropathy, Inflammation, Autoimmune Diseases

THERAPEUTIC AREAS

TARGETS/MECHANISM

PRODUCT/NME

• Cancer

XIAP

Knock Down

2nd Generation Antisense

(AEG35156)

• Cancer• Autoimmune• Inflammation

Pan IAP

Suppression

Small Molecule Inhibitors

•Neuropathic

Pain• Neuropathy

JNK Pathway/

HSP

Small Molecule Modulators

• Cancer• Neuropathy • Pain

Apoptosis Regulation

Small Molecules

Internal Internal Internal In-Licensing/M&A

Proprietary Targets: IAP Protein Family(IAP = “Inhibitor of Apoptosis Protein”)

XIAP Expression in Pancreatic Cancer

• Gene family discovered by Aegera

• Central role in apoptosis inhibition

• Strong correlation with cancer staging, outcome and resistance

• Dominant/fundamental IP on family

“The IAPs…are the most powerful intrinsic inhibitors of cell death. …

.IAP antagonists are promising candidates for anticancer

therapies…” U. Fischer, K. Schulze-Osthoff “Apoptosis-based therapies and drug targets”, Cell Death and Differentiation, 2005

XIAP: A Validated Cancer Target

• Cancer cells are highly resistant to apoptosis; yet in many cases are primed for apoptosis

• XIAP inhibits caspase activities coupled to both intrinsic & extrinsic apoptotic pathways (caspases 3,7,9)

• When XIAP is elevated caspase-dependent apoptosis can’t occur

• Inhibiting XIAP lowers the apoptotic threshold in cancer cells when challenged with CT agents

• Clinically, XIAP expression/regulation correlates with prognosis (AML, renal, prostate, etc..)

•TNF•TRAIL•Fas

JNK

CASPASE 3

CASPASE 9

MITO

Cyto C

CASPASE 7

Bad Bim

Cell Survival

HSP70HSP5 others ...

HSF1HSF1HSF1

HSP70

HSF1 Induces HSP70

HSF1

HSF1 HSP90

Compounds bind to HSP90 and release HSF1

HSP70 potently Inhibits JNK

Aegera Compounds Demonstrate Neuroprotective Activity and Pain Relief

Pain Relief&

RNAi suppression of HSP70 blockscmpd-induced JNK inhibition

Cmpds fail to induce HSP70 in HSF1 knock out cells

Potential Therapeutic Areas Based on MOA

Ischemia & Stroke(excitotoxicity) CDT CNS Neuro Disorders 63-7 [2005]

Alzheimer’s DiseaseAm J Alz Other Demen 79-88 [2002]

Parkinson’sDiseaseIUBMB Life 267-71 [2003]

Huntington’sDiseaseNeuroscience 859-70 [2004]

Diabetic NeuropathyDiabetic NeuropathyFASEB 15: 2508 [2001]JBC 278: 23151 [2003]Diabetologia 49(3): 580 [2006]Mol Pharm. 70:1246 [2006]

Taxol NeurotoxicityTaxol NeurotoxicityJ. Neurosci. 21: 4657 [2001]JBC 278: 567 [2003]

Neuropathic PainNeuropathic Pain Pain 99: 175 [2002]Biochem. Biophys. Res.Comm. 335: 132 [2005]J. Neurosci. 26(13): 3551 [2006]

Axotomy-inducedNeuronal DeathJBC 280: 1132 [2005]

HIV-induced PNExp. Neurol. 188: 246 [2004]Stress-induced Death

of SCGs and DRGsJBC 276: 4531 [2001]

CNS PNS

Experienced Management Team

Shire, Biochem Pharma, NCI (National Cancer Institute)

26VP ClinicalJacques Jolivet, M.D.

NRC, U of Ottawa, Salk Institute

28VP Drug Discovery Jon Durkin, Ph.D.

Telecom, TD Securities18Chief Operating Officer &

Chief Financial Officer

Donald Olds, M.Sc., MBA

BioChem Pharma, Merck29Chief Scientific OfficerJohn Gillard, Ph.D.

RCT, AEA Investors, Bayer, Pfizer

24President & CEOMichael Berendt, Ph.D.

Prior ExperienceYears of ExperienceTitleName

Aegera Development Pipeline

CANDIDATECANDIDATESELECTIONSELECTION PHASE 1PHASE 1 PHASE 2PHASE 2 PHASE 3PHASE 3

AEG35156

Small MoleculeIAP Antagonists

Mono

Small MoleculeNeuropathy/Pain

Combination

Aegera Development Pipeline - 2008

CANDIDATECANDIDATESELECTIONSELECTION PHASE 1PHASE 1 PHASE 2PHASE 2 PHASE 3PHASE 3

AEG35156

Small MoleculeIAP Antagonists

Mono

Small MoleculeNeuropathy/Pain

Combination

Small MoleculeLicensed

Aegera In-Licensing Criteria

• Small molecule therapeutic addressing unmet medical needs in either oncology, peripheral neuropathies or pain;

• Direct activity on a known and biologically validated target preferentially involved in apoptosis control;

• Primary indication that will allow a meaningful clinical readout in a Phase 2 study;

• Lead compound no more than 6-12 months from IND filing up to Phase 3 (with an emphasis on proof of principle);

• High quality preclinical or clinical data from well planned and administered preclinical models or trials;

• Market potential of $ 250M or greater;

• Solid and expandable intellectual property base

Contact:

Aegera Therapeutics Inc.810 Chemin du GolfMontreal, Quebec

H3E 1A8T: 514-288-5532; F: 514-288-9280

www.aegera.com

What’s My Job Like?What’s My Job Like? Try to find strategic partners for our programs

(out-licensing/partnering) Shop for drug programs which complement our

current pipeline (in-licensing) Explore/seek M&A opportunities Member of the R&D Management Committee Secretary of the Licensing Review Committee Represent BD/Licensing in internal program

team meetings – align R&D and business objectives

Competitive business intelligence & market research

Take care of marketing on the side

What’s NextWhat’s Next

Expand my skill set/experience in BD/Licensing Continue contributing to Aegera’s growth Experience an IPO or major acquisition Keep my options open – large biotech/pharma, equity

analyst....

.....in a few years, with more experience and even less hair, if an opportunity comes along......maybe start-up a new company!!

Thank You!Thank You!