Pan metics non confidential 2-21-12

ANTYRAThe Next Generation of Biologicals

PanMetics

For Additional Information:Neil Goldstein, Ph.D.

Chief Scientific [email protected]

Website: www.panmetics.com

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mailto:[email protected]


• PanMetics is a newly formed biotechnology company developing

a powerful array of novel, targeted therapeutic leads against

cancers with high mortality rates and poor therapeutic options

such as Pancreatic Cancer.

• PanMetics has an exclusive license to develop a novel

scaffold, PanM-429, as a drug lead and as a vehicle for delivery

of therapeutic payloads.

Strategic Goals

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Company Overview

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•Cancers such as Pancreatic are unmet medical needs with poor survival rates.

•IGF-1R is a validated target for Pancreatic and other cancers.

•PanM-429 is Mini-protein which acts as an IGF-1R antagonist and inhibits thegrowth of established human pancreatic cancer tumors in animal models.

•PanM-429 is also a “core scaffold” used to generate other therapeutic drugleads including Bi-specifics, which inhibit multiple targets, and as a deliveryvehicle for payloads such as small molecule drugs, siRNA and other biologicaltherapeutics (Cell Penetrating Peptides [CPPs]).

•With a $10M tranched investment, PanMetics will complete Phase 1 clinicaltrials for at least 2 drug leads over a 3 year timeframe.


Cost Basis & Rationale

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•PanMetics is looking for an initial investment $10M for 3 years to complete the following:

• Complete a Phase 1 trial for PamM-429 alone or in combination with approved drugs•Generate and characterized PanM-429 derivatives (Bi-specifics and CPPs)•Identify 1-2 PanM-429 derivatives for clinical development•Complete 2nd Phase I trial for a PanM-429 derivative with an approved drug

•The investment can be paid in tranches and additional funding be based on •Go/No Go decisions

•PanMetics believes that the drug leads generated from these studies are valuable commodities and will generate strong interest from pharmaceutical companies who are constantly looking for novel drug leads and ways to deliver their own

products in a highly specific manner.


Exit Strategy

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•PanMetics believes that its focused drug development strategywill be amply rewarded through investment from both thefinancial community and pharmaceutical licensing deals.

•Expected exit strategies include:

•Buyout by a large pharma or biotech company•M&A with a biotech with synergistic technologies (e.g., siRNA delivery)•IPO/Reverse Merger under the appropriate conditions


The Medical Opportunity

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• The Insulin-like growth factor (IGF) signaling axis is a focus for developingtargeted drugs for treatment of indications including cancer.

• Preclinical research and clinical investigations have implicated the IGF type1 receptor (IGF-1R) and its ligands IGF-I and IGF-II in the development andprogression of a number of human cancers includingpancreatic, ovarian, colorectal, prostate and hematopoietic tumors.

• Targeting the IGF-1R receptor represents an important new approach incancer therapy. PanMetics intends to use its PanM-429 core scaffold togenerate drug leads which will inhibit the IGF-1R cancer axis.

The Target: IGF-1R

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PanM-429 is a Novel IGF-1R Antagonist

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• PanM-429 is a member of a class of novel, highly specific bioactive Mini-Proteins called Peptimetics which act as agonists or antagonists and canbe generated for any disease indication.

• PanM-429 is an IGF-1R antagonist with high affinity and selectivity

• Because of its high specificity and biological activity, PanM-429 can beused as a therapeutic in its own right as well as in combination withapproved drugs for Pancreatic and other cancers.

• In addition to its value as a drug lead, PanM-429 can also be used togenerate novel derivatives such as Bi-specifics and CPPs to deliverpayloads such as small molecule and biological drugs.


PanMetics’ R&D Goals

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•Fully characterize PanM-429 as a therapeutic lead in animal models alone andin combination with approved drugs such as gemcitabine (Gemzar) and Tacerva

•Generate novel derivatives of PanM-429 including Bi-specific and CPPs.

•Bi-specifics which inhibit multiple targets such as IGF-1R/EGFR & IGF-1R/FGFR1

•Cell Penetrating Peptides to deliver a vast array of therapeutics including smallmolecules and biologicals such as, but not limited to, siRNA and antisenseoligonucleotides

•Characterize these entities in vitro and in the appropriate animal models

•Identify 2 drug leads for clinical development (manufacturing, PK/ADMET)

•Complete two Phase 1 clinical trials by the end of Year 3 for these 2 drug leads


PanM-429: A Drug Lead for Treating Pancreatic Cancer

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PanM-429: A Mini-Protein which

Inhibits the IGF-1R

• Affinity = ~300nM = ligand (IGF-1)

• In vitro properties– Blocks IGF-I induced phosphorylation of IGF-IR

– Inhibits IGF-IR/IR hybrid receptors

– Specificity for IGF-1R vs IR

– Inhibits IGF-I induced proliferation in cell assays

• Inhibits tumor growth in vivo

• Predicted to weakly immunogenic (by analysis)

• Indication: Pancreatic Cancer (& other cancers)

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PanM-429 inhibits the Growth of

Pancreatic Cancer Cells in Animals

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Injections (ROI = SC): 4/week x 3

*Control Vehicle 429-300 429-50 G12-300

**

Established Tumors >100mm3

Control

Tumor Growth Tumor Weight

Control Vehicle 5-FU 429 300 429 50

Tum

or

Weig

ht (g

)

0.0

0.5

1.0

1.5

2.0

2.5

DAYS

0 5 10 15 20 25 30

Tum

or

Volu

me (

mm

3)

0

500

1000

1500

2000

2500

3000

Control

Vehicle

ANT-429 300

ANT-429 50

ANT-G12 300

429 300

429 50

PanM-429 inhibits the growth of established MiaPaCa tumors growing in nude mice


PanM-429 as a Scaffold for Novel Therapeutic Derivatives

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Generation of Bi-specifics with PanM-429

5mer Linker429 Sequence Target Binding Sequence

Pan vs. 2nd Target (EGFR, FRGR1, etc.)

5mer Linker429 Sequence 15mer Random Sequence

•Screen in ELISA vs IGF-1R & 2nd Target

•Move to secretory vector for transfections studies

•Synthesize HP and test in cell-based assays

•Determine efficacy in animal models

•Library can be used for any 2ary target

Screen

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PanM-429 as Bi-specific Cell Penetrating

Peptide

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‣PanM-429 internalizes into various cell types including Pancreatic

Cancer

‣PanM-429 can be used to deliver therapeutic payloads such as

siRNA, antisense, biologicals and small molecules.

‣PanM-429 conjugated to a payload can be considered “Bi-specific”

because both the Peptimetic and the payload have biological

activity.


PanM-429 Conjugated to a Payload

5’ or 3’ linkage to PanM-429

Utilize well established chemistry

PanM-429 is cationic and help shield net negative charge on siRNA and other biologicals

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• Enzymatic• Chemical• Endosomal

• siRNA (single or ds)• Antisense•Small Molecule Drugs•Biologicals

Chemical Linker[Stable or Cleavable ]PanM-429


The Investment Opportunity

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Year 1 Year 2 Year 3

• Full Characterization of PanM-429

• Develop PanM-429 Bi-specifics (with EGFR and FGFR1)

•Develop PanM-429 delivery conjugates with gemcitabine & cis-platin

•Develop PanM-429 delivery conjugates with Kras antisense

•Develop PanM-429 directed liposomes with Kras siRNA

•Animal studies with PanM-429

•Begin Manufacturing Lead 1

•SBIRs to supplement investor funding

• Complete Phase 1 for Lead 1 and full data package (Q3)

• Lead 2 IND

•Complete Phase 1 for Lead 2 and full data package (Q4)

• Business Development : partnering deal(s) for drug leads 1&2 and/or other PanM-429 derivatives in pre-clinical

•Pre-clinical development of additional leads

• Continue animal studies with PanM-429 and derivatives

• PK and ADMET Lead 1

•Lead 1 IND (Q4)

•Begin Manufacturing Lead 2

•Develop a full pre-clinical package for partnering and licensing discussions with pharma/biotech companies

Business Development opportunities

PanMetics’ Business Strategy

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$10M Seed Investment: Tranched based on milestones


Risks:Unanticipated technical issues/delays Slower than forecasted development timelines Slower than expected BD licensing deals

Potential: Faster than expected development timelines for PanM-429 &

derivatives Rapid characterization of Lead 1: e.g., PanM-429 Rapid development of Lead 2: e.g., PanM-429 –gemcitabine

conjugate

Identification of additional leads with therapeutic potentialEarly licensing/partnering deal brings non-dilutional funds

and clinical expertise into company

Business Development: Risks & Potential

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Competitive Landscape for IGF-1R Cancer

Drugs

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Drug Company Clinical Trial Cancer(s) Target(s) Type Continuing?

XL228 Exelixis Two Phase 1s

(updated 2011)

CML IGF-1R, src,

BCR-ABL

Small

molecule

Both Studies

terminated?

OSI 906 OSI Phase I ACC IGFR, IR Small

Molecule

ongoing

AMG-479 Amgen/Takeda Phase I/II

Phase III (+

Gemzar)

Multiple solid

tumors

Pancreatic

IGFR MAB ongoing

R 1507 Roche Phase I Sarcoma IGFR MAB Stopped

development

Figitumumab Pfizer Phase I Multiple solid

tumors

IGFR MAB Stopped

development

BMS-754807 BMS Phase I Multiple solid

tumors

IGFR, IR Small

molecule

ongoing

MK0646 Merck Phase I +/-

Gemzar+/-

erlotinib

Pancreatic IGFR MAB ongoing

Cixutumumab

(IMC A12)

Lilly (from

ImClone)

Phase I +

temsirolimus

Multiple solid

tumors

IGFR MAB ongoing


PanMetics Has the Therapeutic Edge

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•PanMedics believes that PanM-429 and its derivatives will be effectivealone and in combination with any approved drugs to increase thetherapeutic index for IGF-1R expressing cancers such as Pancreatic.

•PanM-429 is cheaper to produce than monoclonal antibodies and vaccines(=decreased COGs).

•PanM-429 Bi-specifics will inhibit multiple targets thereby increasingselectivity, potency and therapeutic index.

•PanM-429 conjugated to small molecules and biologicals will be able totarget internal targets inaccessible to monoclonal antibodies


Assets and Capabilities

PanM-429 has already shown efficacy in vivo

PanM-429 Bi-specific and delivery modules are available &

tested in vitro

Hugh pipeline potential

Proven scientific approach

Strong IP base, proprietary reagents and know-how poised

to move 2 Leads through clinical trials within 3 years

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PanMetics

For Additional Information:Neil Goldstein, Ph.D.

Chief Scientific [email protected]

Website: www.panmetics.com

Non-Confidential 23

mailto:[email protected]


PanMetics: 5 Year Plan

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•Primary Opportunities: Years 1-3•Move 2 drug leads through Phase I Clinical Trials

•Secondary Opportunities: Years 1-3•Continued pre-clinical development of additional PanM-429 derivatives forpartnering/licensing and downstream INDs

•Round B financing = $7.5M: Years 4-5•Move additional drug leads into Phase I Clinical Trials (from PanM-429derivative pool)•Identify new targets for Pancreatic Cancer and generate novel Peptimeticantagonists for pre-clinical development•Develop antagonists for additional high mortality/untreatable cancers

Phase II Clinical study(s): With additional financing for Years 4-5 ($15-20M)PanMetics would be able to move one of its drug leads into a Phase II trial. Itis anticipated that this would be done in partnership with a largepharmaceutical/biotech company

Technology

Pan metics non confidential 2-21-12