"Our TPTs are designed specifically to offer patients new therapies that
improve upon, and overcome the challenges of, existing therapeutic
options," said Stephen Hurly, President and Chief Executive Officer of
"We are also encouraged by the preclinical results with our proprietary de-immunized payload, deBouganin. These data suggest that deBouganin is not subject to the same multi-drug resistance mechanisms that hinder the efficacy of traditional ADCs and small molecule therapeutics. Coupled with its picomolar killing, broad therapeutic window and potential effect against cancer stem cells, we believe deBouganin has the potential to serve as the basis for next-generation therapies with activity in a broad spectrum of cancers."
Abstract 614: VB4-845 tumor cell killing in a combination study with the anti-PD1, nivolumab
Data suggest that VB4-845 induces the expression of HMGB1 in treated tumor cells. HMGB1 is one of three DAMPs markers that indicate that a tumor cell is undergoing ICD. Eleven has previously disclosed the observation of the two other DAMPs markers - cell surface expression of calreticulin and extracellular release of ATP - following treatment with VB4-845. Together, these results suggest that Eleven's product candidates formulated with VB4-845 (Vicinium and Proxinium) are capable of inducing host anti-tumor immune responses. In preclinical models, immunocompetent mice treated with both VB4-845 and the anti-PD1 nivolumab exhibited circulating T cells and intratumoral T cells, which suggests such an anti-tumor immune response.
Based on these data, Eleven believes that combination treatment with its product candidates formulated with VB4-845 (Vicinium and Proxinium) can facilitate and augment checkpoint inhibitor anti-tumor activity. These results support the Company's plans to initiate a Phase 1/2a clinical trial evaluating Proxinium in combination with a checkpoint inhibitor in the second half of 2017.
Abstract 79: Trastuzumab and C6.5 diabody armed with deBouganin overcome drug resistance to ADCs comprised of anti-microtubule agents
Data suggest that Eleven's deBouganin payload is capable of effectively killing tumor cells that are resistant to treatment with ADCs composed of the anti-mitotic payloads DM-1 and MMAE when conjugated to the same monoclonal antibody, trastuzumab. Preclinical data suggest that this is due, in part, to deBouganin's lack of sensitivity to the multidrug resistance pumps that allow some cancers to escape the action of anti-mitotic ADCs and to changes in the phosphorylation status of proteins involved in cell proliferation (JNK, MAPK, and AKT) or cell survival (BCl-xL and MCl-1).
Based on these findings, Eleven believes that deBouganin is capable of overcoming mechanisms of resistance being employed by cancer cells against ADC payloads and that it may therefore represent a more effective therapeutic option. The Company plans to file an investigational new drug application (IND) for VB6-845d, it's lead systemically-administered TPT, in the first quarter of 2018.
Both poster presentations are available on the "Investors & Media" page of Eleven's website under "Events & Presentations" at www.elevenbio.com.
Cautionary Note on Forward-Looking Statements:
Any statements in this press release about future expectations, plans
and prospects for the Company, the Company's strategy, future
operations, and other statements containing the words "anticipate,"
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"continue," and similar expressions, constitute forward-looking
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Reform Act of 1995. Actual results may differ materially from those
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ability to successfully develop our product candidates and complete our
planned clinical programs, our ability to obtain marketing approvals for
our product candidates, expectations regarding our ongoing pre-clinical
studies and clinical trials, availability and timing of data from
pre-clinical studies and clinical trials, whether interim results from a
pre-clinical study or clinical trial will be predictive of the final
results of the study or trial or results of early pre-clinical and
clinical studies will be indicative of the results of future studies,
the adequacy of any clinical models, expectations regarding regulatory
approvals, and other factors discussed in the "Risk Factors" section of
the Company's Annual Report on Form 10-K, Quarterly Reports on Form 10-Q
and other reports filed with the
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