Antigen-specific prime boost
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 soft tissue sarcoma, the lead indication we are studying in Phase 1 and 2 clinical studies. 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 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 both our monotherapy single arm Phase 1 and combination randomized Phase 2 studies, 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. By comparison, to date, both CMB305 and LV305 have a very favorable safety profile in Sarcoma patients. We believe CMB305’s potential benefit to patients will be the combination of a favorable safety profile with improved survival, and as such are focused on overall survival and safety as the primary endpoints of these studies.
Status: CMB305 is currently in several stages of clinical development, including a monotherapy Phase 1 trial and a fully-enrolled randomized Phase 2 trial, primarilyin patients with two subtypes of soft tissue sarcoma (synovial sarcoma or myxoid/round-cell liposarcoma). In the combination study, patients receive either CMB305 combined with Genentech’s cancer immunotherapy, TECENTRIQ® (atezolizumab, anti-PD-L1), or atezolizumab alone, pursuant to a collaboration with Genentech.
At the American Society of Clinical Oncology (ASCO) 2017 Annual Meeting, we reported positive clinical and biomarker data for CMB305 monotherapy. In 25 soft tissue sarcoma (STS) patients with recurrent disease treated with CMB305, median overall survival (mOS) had still not yet been reached, with an overall survival rate at 12 and 18 months of 83% and 76%, respectively. These data compare favorably to mOS for approved second line and later sarcoma agents, which is only 12.4-13.5 months, as well as a published mOS of 11.7 months for synovial sarcoma patients specifically; the largest patient population enrolled in this trial. A disease control rate (DCR) of 64% (16/25) was observed, including durable tumor growth arrest in patients who had evidence of disease progression at study entry. Also, CMB305 was well tolerated, and generated a strong and broad anti-NY-ESO-1 immune response in >50% of the patients, including evidence of antigen spreading – the induction of an immune response against other tumor antigens not targeted by CMB305. In addition, we presented data showing a statistically-significant association of an induced response and clinical benefit in a pooled set of patients treated with CMB305 or LV305. The immune biomarkers studied, including novel bio-markers derived from public TCRS (pTCRs), may guide regulatory strategy via the selection of patients more likely to have survival benefit on CMB305 therapy benchmarks. (See Presentations)
We have received Orphan Drug Designation in STS for both components of CMB305 in both the US and EU, and for CMB305 in the US. 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.
Potent Intratumoral TLR4 agonism
Potent Intratumoral TLR4 agonism
- Intratumoral immune activation of the tumor microenvironment
- Designed to leverage endogenous antigens and create a systemic immune response
- Generated from GLAAS®
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 to create a systemic anti-tumor immune response from local injection. 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 being studied in a fully-enrolled randomized Phase 2 trial in patients with follicular non-Hodgkin Lymphoma (FL) in combination with local radiation and Merck’s anti-PD-1 agent, pembrolizumab, pursuant to a clinical collaboration with Merck. At the American Society of Clinical Oncology (ASCO) 2017 Annual Meeting, we presented monotherapy data of nine patients who received G100 with radiation (no pembrolizumab) that showed 100% DCR rate, with 44% of the patients achieved a partial response (PR) based on WHO criteria, which requires at least a 50% tumor reduction to qualify as a PR. In addition, 50% of evaluable patients experienced shrinkage of untreated distal (abscopal) lesion. G100 was well tolerated, with no related Grade 3/4 AEs in all three dose levels tested, and tumor biopsies showed increased inflammatory responses and T cell infiltrates in abscopal, non-treated tumors. (See Presentations)
We have received Orphan Drug Designation in follicular FL for G100 in the US. If the ongoing trial in FL patients produces a sufficiently robust clinical benefit for patients, we may pursue FL as the first indication for which we intend to seek regulatory approval for G100. In addition, 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.
- Novel, multi-payload 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, with immunostimulatory molecules
- Will be generated from the evolution of the ZVex discovery platform
About LA51: We intend LA51 and our other potential next-generation approaches 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, these next-gen ZVex agents will be designed to produce personalized neoantigen-based immunotherapies, as well. In contrast to other approaches, we believe the new payload 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 next-gen product candidate, LA51, in 2017.