CVM-Pharmacy Spring SymposiumCVM-Pharmacy Spring SymposiumWhat CVM has to Offer (Oncology) What CVM has to Offer (Oncology)

(ACCR)(ACCR)

Jaime F. ModianoJaime F. Modiano

The Animal Cancer Care and Research Program (ACCR)

• Joint program of CVM and MCC

• Basic, translational, and clinical research mission

• Educational and training mission

• Clinical service delivery mission

Onc Section Faculty and Research Interests

• Jaime Modiano – Professor– Cancer biology, immunology, genetics

• Mike Henson – Associate Professor– Translational therapy

• Fekadu Kassie – Assistant Professor– Cancer chemoprevention

• Erin Dickerson – Assistant Professor– Drug targeting and cancer metabolism

• Antonella Borgatti – Assistant Professor– Translational therapy

• Daisuke Ito – Assistant Professor (6/1/13)– Lymphoma biology

• Claire Cannon – Research Associate (Onc Fellow)– Translational therapy

Other ACCR Faculty

• Liz Pluhar and Vicki Wilke (CVM, Surgery)• Subree Subramanian (SOM - Surgery)• Aaron Sarver (MCC)• David Largaespada (MCDBG)• Khalil Ahmed (VA and SOM, LMP)• Jeff Miller (SOM, Medicine)• Dan Vallera (SOM, Radiology)• Many others

Research Opportunities

• > 1 million dogs are diagnosed and managed with cancer in the U.S. each year

• Intact immune system• Compressed life span• Cancers are influenced by similar factors (e.g. age,

nutrition, gender, reproductive state, environmental exposure) www.canusgoatsmilk.com

Key Programs• Brain cancer (Pluhar, Moertel)

• Sarcomas (Borgatti, Weigel, Largaespada, Spector, Wilke, Sarver, Subramanian, Modiano, Dickerson, Clohisy, et. al.)

• Hematologic malignancies (Ito, Miller, Modiano, O’Brien, Linden, Bachanova, Burns)

• Chemical carcinogenesis and prevention (Kassie)

• Etiology and cancer genetics (Modiano, Sarver, Subramanian, Largaespada, O’Brien, Kassie)

• Therapeutic targeting and microRNAs (Subramanian, Dickerson, Vallera, Ahmed, Kassie)

• Clinical trials (Borgatti, Henson, Cannon)

Resources• Tissue bank

– >100 cell lines (mostly sarcomas) and >1200 tumor samples with blood for germ line DNA (e.g., T:N sequencing) with broad geographic distribution

– Bank was developed as a joint effort with collaborators at Broad and NCSU, and supplemented from local patient samples and from U of M clinical studies

Clinical Opportunities

• Studies originating locally (home grown therapies)

• Studies originating from contracts or collaborations (imported technology)

• Hypothesis testing and hypothesis generating

Tumor Distribution at the CVMAll Admissions

Tumor Distribution at the CVMNew Diagnoses

- New Diagnoses

Clinical Oncology Studies at the CVMLymphoma

(LSA)

Karyo-1 CRM1 inhibitor

Safety, dose-finding study

Dogs with lymphoma, otherwise healthy

Fully funded Borgatti C

LSA Karyo-2 CRM1 inhibitor

Efficacy study

Dogs with naïve and first relapsed lymphoma, otherwise healthy

Fully funded Borgatti A

LSA MADGIC Sample collection study

Discovery and characterization of heritable and somatic cancer mutations in Golden Retrievers

Dogs with lymphoma Biopsy samples and blood samples

Modiano A

LSA LICKing Lymphoma

PSC-833

Ablation of tumor initiating cells, safety and efficacy study with concurrent doxorubicin chemotherapy

Dogs with lymphoma, otherwise healthy

Study drug

$2,000 to owners towards chemotherapy

Modiano C

LSA Idarubicin Prospective, open- label, phase I

Dogs with measurable lymphoma

Study costs Husbands C

LSA Acupuncture Efficacy of acupuncture in alleviating chemotherapy-induced side effects

Concurrent doxorubicin chemotherapy

Randomized, double-blinded

Dogs with lymphoma Covers the cost of acupuncture

Choi P

Disease Study Description Inclusion/exclusion Incentive PI Status

Brain tumors

(Glioma,

Meningioma)

1) Gene therapy + immunotherapy vs. immunotherapy alone

2) Gene therapy + chemotherapy

3) Immunotherapy + chemotherapy

Study selected based on diagnosis

MRI prior to enrollment

No evidence of systemic disease

Fully funded Pluhar A

Any histology,

*histiocytic sarcoma

Compassionate use of TTG100 in canine spontaneous cancer

Safety and efficacy of TTG100

ECG, PK series, Visits Day 1, 22, 43, 71, 99

Any measurable disease

SOC not successful or declined

No anticancer therapy for at least 3 weeks prior to enrollment

Drug and PK levels covered

$1,000 credit + $1,000 credit to owners of Bernese Mountain Dogs (from breed club)

Henson A

Various histologies

*liver cancer

Microwave ablation + immunotherapy

Safety and efficacy of ultrasound-guided microwave ablation combined with adjuvant

Dogs and cats with unresectable masses amenable to microwave ablation

Partially-funded Ober A

Any histology, including breed specific cohorts

COTC016: A Pilot Study Assess feasibility of tissue collections and molecular profiling for future comparative oncology personalized medicine

Any measurable disease

$1,000 credit to owners + costs associated with sample collection

Henson C

Disease Study Inclusion/exclusionDescription Incentive PI

Clinical Oncology Studies at the CVMStatus

Clinical Oncology Studies at the CVMHemangiosarcoma (HSA)

1) SRCBST

Bispecific ligand targeted toxin

2) MADGIC

Dose-finding

Splenectomy and doxorubicin chemotherapy

PET-CT at baseline and on day 21 if abnormalities on the initial scan

PK samples

Sample collection

Splenic HSA

No evidence of metastasis

Enrollment post splenectomy

All dogs with HSA

Study rechecks are covered + $3,300 towards SOC chemotherapy

Samples/pathology

Modiano A

Borgatti

Vallera

Modiano A

Osteosarcoma

(OS)

1) OSAL (Salmonella-IL2)

2) miR31

Safety and efficacy

Concurrent doxorubicin chemotherapy

Markers of pulmonary metastatic disease

Naïve appendicular OS

Naïve appendicular OS

$2,000 incentive

Pays sample collection

Wilke A

Kassie A

Fritz

OS Palladia/Piroxicam/Cyclophosphamide maintenance therapy

Impact and efficacy of maintenance therapy following amputation and carboplatin

Microscopic, non-metastatic OS

Partially-funded Borgatti C

Feline oral squamous cell carcinoma (SCC)

Protein kinase CK2 (nanocapsules)

Safety and efficacy Oral SCC, regional metastasis permitted, no distant metastasis or systemic disease

Treatment, rechecks, up to $2,500 towards adverse events

Cannon A

Disease Study Description Inclusion/exclusion Incentive PI Status

Clinical Investigation Center (CIC)

What Else Sets the UMN Apart?A Few Select Examples:• Translation of brain cancer therapy from dogs to humans

– “Successful Cancer Trial In Dogs Helping To Save Teenager”• Prediction and prognosis for bone cancer patients

– “U of M researchers look to dogs to better understand intricacies of bone cancer”

• Translation of cancer therapies from humans to dogs and back– Sal-IL-2 for bone cancer– Minnelide™ for bone cancer– “LICKing Lymphoma” – Novartis partnership targeting tumor

initiating cells– Bispecific Ligand Targeted Toxin for hemangiosarcoma– Gene therapy for liver tumors

What Have We Accomplished?

• Research success has allowed us to establish a level of credibility in the scientific community and created a stable partnership between CVM and MCC

• Success stories extend from the laboratory to the clinic – advancing translation