CMB305 / LV305 / G100

Pipeline

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Preclinical Phase 1 Phase 2 Phase 3

Immuno-oncology Pipeline

CMB305

Antigen-specific prime boost

Targeting NY-ESO-1
Phase 1 & 2 Tumors
Studies Ongoing (Orphan & High Incidence)

CMB305

Antigen-specific prime boost

  • Prime-Boost Immuno-Oncology Agent
  • In vivo T cell activation
  • Combines two agents designed to target NY-ESO-1-expressing tumors via different mechanisms

About CMB305: CMB305 is a prime-boost approach designed to target tumors that express the NY-ESO-1 tumor antigen, such as the indication we are studying in Phase 2, soft tissue sarcoma. NY-ESO-1 is expressed in a large number of solid and liquid tumors in varying degrees. CMB305 consists of a “prime” called LV305 from our ZVex platform dosed sequentially with a “boost” called G305 from our GLAAS platform. Together, they are designed to induce a synergistic anti-tumor cytotoxic T lymphocyte (CTL) response targeting NY-ESO-1-expressing tumors. CMB305 may also generate memory CTLs, and therefore long-term immune surveillance, as well as enhance other immune anti-tumor mechanisms.

Soft Tissue Sarcoma Opportunity: in our randomized Phase 2 study, we are focusing on two types of sarcoma where we believe there is significant unmet need: synovial sarcoma and Myxoid round cell liposarcoma. Synovial sarcoma is a cancer in the joints with a five-year and ten-year survival for people with Grade 3 tumors or metastatic disease of less than 25% and 15%, respectively, and Myxoid round cell liposarcoma is a malignant tumor that most often occurs in the deep-seated soft tissues of the extremities. Currently marketed treatments have high toxicity, with up to 37% of patients experiencing Grade 3/4 Adverse Events. In comparison, to date, no sarcoma patients receiving either CMB305 or LV305 have experienced above a Grade 2 adverse event. We have received Orphan Drug Designation in STS for both components of CMB305 (LV305 and G305) in both the US and EU.

Status: CMB305 is currently in several stages of clinical development, including a randomized Phase 2 trial in patients with two subtypes of soft tissue sarcoma (synovial sarcoma or myxoid/round-cell liposarcoma) who receive either CMB305 combined with Genentech’s cancer immunotherapy, TECENTRIQ® (atezolizumab, anti-PD-L1), or atezolizumab alone, pursuant to a collaboration with Genentech. At our company update for investors and analysts in June 2016, we reported a preliminary analysis of the first 14 patients in our CMB305 Phase 1 single agent trial in patients with NY-ESO-1 positive soft tissue sarcomas, as follows: Median OS has not been reached. 93% (13/14 patients) survival to date; Median PFS is 5.5 months; Best response to date is stable disease (10/14, 71%); and the Safety profile is very favorable, with only Grade 1/2 AE. (See Press Release) We have received orphan drug designation in the US and EU for each component of CMB305 for soft tissue sarcoma. If the ongoing trials produce a sufficiently robust clinical benefit for patients, we plan to pursue soft tissue sarcoma as the first indication for which we intend to seek regulatory approval for CMB305. Please check the clinical trials page for more information.

LV305

Antigen-specific ZVex® vector

Targeting NY-ESO-1 Tumors (Orphan & High Incidence)

LV305

Antigen-specific ZVex® vector

  • In vivo T cell active immunotherapy
    1. Designed to target NY-ESO-1-expressing tumors
  • Generated from ZVex® Discovery Platform

About LV305:  LV305, a product of our ZVex platform, is designed to specifically target dendritic cells (DCs) in vivo and cause the induction of NY-ESO-1-specific CTLs. LV305 is one of the two components of our CMB305 product candidate, and was one of our earliest programs to enter clinical development. As a ZVex-based product, LV305 is highly specific for DCs, is unable to integrate or replicate effectively, and is engineered to selectively activate CTLs without inducing CTL exhaustion, all with a desirable safety profile that we believe should result in an improvement over earlier vector approaches.

Status: We completed enrollment of a Phase 1 dose-escalation clinical study of LV305 in a defined patient population with solid tumors expressing the NY-ESO-1 tumor antigen. In a February 2016 press release, we indicated that LV305 consistently maintained the safety and immunogenicity reported in 2015 at ASCO, but with an improved clinical benefit profile in patients with soft tissue sarcoma. (View ASCO Poster). As of the end of the third quarter 2016, the median OS for LV305 in STS patients had still not been reached (n=23).

Future Development: Because of its prime-boost approach, Immune Design believes CMB305 should be more effective than LV305. Although we currently intend to focus development efforts on CMB305 and G100, the LV305 expansion trial was designed to potentially provide data to support the further development of LV305, either alone or in combination with another immunotherapy such as a checkpoint inhibitor.

G100

G100 Intratumoral TLR4 agonism

Leverages Endogenous & Neo Antigens Follicular Non-Hodgkin’s Lymphoma

G100

G100 Intratumoral TLR4 agonism

  • Intratumoral immune activation
  • Designed to leverage endogenous antigens
  • Generated from GLAAS™ discovery platform

About G100: G100 is Immune Design’s first product candidate solely generated from the GLAAS™ platform and is designed to leverage the range of endogenous antigens (including neoantigens) found in the tumor microenvironment. At its core, G100 consists of Glucopyranosyl Lipid A (GLA), a potent small synthetic molecule that selectively binds to the Toll-like Receptor-4 (TLR4) receptor. , We believe that when G100 is administered with mechanisms that kill, or lyse, tumor cells (such as radiation), it may cause dendritic cells near the lysed tumor to activate and capture the wide range of released endogenous tumor antigens. G100 is designed to trigger a broad immune response against those newly-encountered antigens.

Status: G100 is currently enrolling patients in a randomized Phase 2 trial in patients with follicular non-Hodgkin Lymphoma in combination with local radiation and Merck’s anti-PD-1 agent, pembrolizumab, pursuant to a clinical collaboration with Merck. We also completed a Phase 1 trial in patients with Merkel cell carcinoma (MCC) and presented data on the full patient set at ASCO 2016, including an objective response rate of 50% per protocol and the conversion of “cold” to “hot” tumors in responding patients. (See Press Release. View ASCO Poster.) The accessibility of certain tumors makes them ideal for intratumoral dosing, and we plan to evaluate the potential of additional clinical studies in other tumors. Please check the clinical trials page for more information.

ZVex2.0

Novel dendritic cell targeting vector

Targeting multiple conserved and/or patient-specific Neo-antigens

ZVex2.0

Novel dendritic cell targeting vector

  • In vivo T cell active immunotherapy
  • Designed to target multiple conserved antigens without antigen competition, as well as patient-specific neoantigens
  • Will be generated from the evolution of the ZVex discovery platform

About ZVex2.0: We intend ZVex2.0 to go beyond the current ZVex platform, with the ability to deliver multiple antigens without the risk of antigen competition, as well as immunostimulatory molecules. In addition to conserved antigens, ZVex2.0 will be designed to produce personalized neoantigen-based immunotherapies, as well. In contrast to other approaches, we believe ZVex2.0’s payload capacity and ability to induce a broad immune response will enable us to include a wide range of patient-specific epitopes, thereby addressing the shortcoming of other approaches that require a more narrow selection due to finite vector space and/or antigenic competition.

Status: We plan to designate the first ZVex2.0 product candidate in 2017.

GLAAS Infectious & Allergic Diseases Immunotherapy Pipeline

RSV Vaccine

Partnered

Peanut Allergy Vaccine

Partnered

G103 (HSV-2 Vaccine)

Partnered