Leaders in Pharmaceutical Business Intelligence (LPBI) Group

LIVE 8:25 – 9:30 8/29 REALIZING THE POTENTIAL OF ONCOLYTIC VIRUS IMMUNOTHERAPY @IMMUNO-ONCOLOGY SUMMIT – AUGUST 29-30, 2016 | Marriott Long Wharf Hotel – Boston, MA

http://www.immuno-oncologysummit.com/uploadedFiles/Immuno_Oncology_Summit/Agenda/16/2016-The-Immuno-Oncology-Summit-Brochure.pdf

 

Leaders in Pharmaceutical Business intelligence (LPBI) Group

covers in Real Time the IMMUNO-ONCOLOGY SUMMIT using Social Media

 

Aviva Lev-Ari, PhD, RN,

Founder, LPBI Group & Editor-in-Chief

http://pharmaceuticalintelligence.com

Streaming LIVE @ Marriott Long Wharf Hotel in Boston

Curation of Scientific Content @Leaders in Pharmaceutical Business Intelligence (LPBI) Group, Boston

 

8:25 – 9:30 REALIZING THE POTENTIAL OF ONCOLYTIC VIRUS IMMUNOTHERAPY

 

LIVE 8:25 Chairperson’s Opening Remarks

Brian Champion, Ph.D., Senior Vice President, R&D, PsiOxus Therapeutics Ltd

• Different viruses
• Engineering
• Manufacturing: CMC
• Systemic vs IT Delivery
• Tumor Markers environment: Tumor cell lysis and immune response
• Biomarkers Clinical Development
• Role of Pre-clinical Models
• regulatory affairs

8:30 T-Vec: From Market Approval to Future Plans

Jennifer Gansert, Ph.D., Executive Director, Global Development Lead, IMLYGIC, Amgen, Inc.

Talimogene laherparepvec (T-VEC) is a modified herpes simplex virus type -1 designed to selectively replicate in tumors and to promote an anti-tumor immune response. T-VEC is approved for metastatic melanoma based on a randomized phase III trial; T VEC significantly improved durable response rate vs GM-CSF. Data from the pivotal trial and combination studies with checkpoint inhibitors will be presented.

T-VEC – HSV-1

• Viral Protein:

1. ICP47 – Deleltion ,
2. ICP34.5 – Deletion ,
3. US11 – Temporal expression,
4. GM-CSF – Insertion

• Engineering Change:

1. Injected Tumor
2. Contralateral tumors

• Dual MOA
• Administration: Largest lesion first, 4 cycles of injections
• OpTim – Phase III: N = 436 Stage III-IV Melanoma
• T-VEC (N = 295)
• GM-CSF (N=141)
• Key ENTRY Criteria
• END POINT: Primary and Secondary – Survival benefit
• 2/3 – prior infection with HIV – melanoma not resectable with spread to lymph nodes
• Response rate with T-VEC: 30% response 2/3 – control of the disease
• Lesion-Level, Lesion-Type Response Analysis
• Overal Survival:Over 20% reduction of burdon
• Retrospective analysis: If not spread yet to lymph nodes: Best response to treatment
• Early disease stage and early therapy are correlated
• T-VEC double survival vs GM-CSF
• Adverse effects: Cellulitis

Phase I

Phase II

Phase III

• Regulatort Interactions for US BLA – Full approval in 10/2015
• Rationale for Combination wiht CHeckPoint Inhibitors

1. Immunologic response:
2. Control
3. OncoVEX mGM-CSF
4. CTLA4
5. Ipilimumab – 3
6. Pembrolizumab -4
7. Neoadjuvant – 2
8. unserectable safety  – 1

• Changes in Tumor Burden by DIsease CHange
• Progression-Free Survival – 72%
• Adverse events: as expected
• Phase II design: Pembrolizumab 200mg
• Monotherapy vs Combination
• Address multiple Tumor type: Menaloma, RCC, mCRC, BrCA, Gastric, NSCLC, HCC
• Other: Head & Neck (completed), Pacreatic (completed), Hepatic injection (ongoing), Pediatric study (planned)

9:00 Oncolytic Virotherapies as a Single Shot Cure?

Stephen J. Russell, M.D, Ph.D., Professor, Mayo Clinic

VYRIAD, CEO

Oncolytic virotherapy is increasingly used as a cancer immunotherapy. However, certain oncolytic viruses can also mediate wholesale tumor destruction independently of an antitumor immune response. This is the oncolytic paradigm, where a cytolytic virus with preferential tumor tropism spreads extensively at sites of tumor growth and directly kills the majority of the tumor cells in the body leaving only a few uninfected tumor cells to be controlled by the concomitant antitumor immune response.

• Virus – does the heavy lifting – small virus inoculum, local spread, systemic virus spread – via blood stream -VIREMIA – killing of infected cells Immune response help Virus elimination
• Engineer virus: Tropism, dose, route
• Immune response: Killing Uninfected cells killing tumors cells
• Second exposure – preformed antibodies: Viremia – neutrilized + Memory cytotoxic T-Cells CTL
• Oncolytic ViroTherapyFirst dose more effecitve then subsequence
• VSV- Vesiculat Stomatisis Virus: IFNbeta and NIS
• SIngle dose: Intratumorally: complete regression – controlling tumor
• Reaching mestastesis: IV delivery
• After systemic delivery: Mode of Virus spread in Tumors: tumor distruction: density of tumors: Delivery and SPread
• Second and subsequent – Ovarian Cancer: single dose vs six doses: no significant (three doses – NO additional therapeutic benefit
• Pet-dog with lynphoma: Multi center – single shot
• HUMAN: Clinical Trial in Mayo, Arizona, Redractory/Intolerant HCC: In Patient 12:necrosis of the tumors, markers: HCC – metastasis to ColonRectal Cancer – developed Day 13 Hepatorenal outcome – virus infected non-injected tumors
• NGS – error rat 1 in 1000 of virus genome sequence – 164 mutations 103 coding and 61 are noncoding or silent mutations
• What determined rapid virus spear in Patient12: 4 gees of thr 84 genes:

1. antiviral state
2. antiviral sensing and signaling
3. IFN signaling
4. Antigen processing and presenation

NOW Companion Diagnostics is been developed

CASE: Measles Seronegative: – Complete response to IV MV-NIS  – patient with melanoma

• no systemic response – Oncolytic debulking and lasting immune control

Summary

1. Single shot cure for cancer – and likely transform Cancer care
2. Oncolytic and Immune two MOA – killing infected and uninfected tumor cells

Success: monitor viral spread

1. exploit first dose
2. develop tests to match with tumor
3. combine with immuno modulatory drugs
4. continue create better viruses

VYRIAD: Companion Diagnostic: Lung, Head & Neck, Bladder