Aptevo Therapeutics, a biotech company developing new therapies for blood and lymph cancers, will soon launch a Phase 2 clinical trial to evaluate its monospecific antibody candidate, otlertuzumab, in patients with peripheral T-cell lymphoma (PTCL).
The company also announced a series of new developments in their research program, including the filing of two Investigational New Drug applications to advance the bispecific antibodies (antibodies that target two distinct molecules) APVO436 and APVO210 into clinical development. The drugs are being developed for leukemia and for autoimmune and inflammatory diseases, respectively.
“We continue to make solid progress advancing our ADAPTIR portfolio with the expansion of our otlertuzumab clinical development program to include a new indication in PTCL, as well as planned IND filings for two new ADAPTIR candidates in 2018,” Scott Stromatt, chief medical officer of Aptevo Therapeutics, said in a press release.
Otlertuzumab is a humanized antibody, designed with Aptevo’s Adaptir platform, that targets a protein called CD37, seen on the surface of healthy and cancerous B-cells.
Previous data with animal models showed that treatment with otlertuzumab prevented tumor growth and led to a statistically significant increase in survival.
In a Phase 2 clinical study with chronic lymphocytic leukemia (CLL), otlertuzumab combined with bendamustine (Treanda) significantly delayed disease progression – from 10 to 16 months – compared to bendamustine alone.
“Recently, intriguing evidence has been reported on the overexpression of CD37 on T-cell malignancies, suggesting a potential role for otlertuzumab in an attractive, orphan drug-eligible indication with high unmet medical need,” Stromatt said.
“Based on these developments, Aptevo has decided to expand its existing Phase 2 clinical protocol to evaluate otlertuzumab in PTCL and discontinue enrollment in the ongoing cohorts evaluating otlertuzumab in CLL with the intention of continuing to explore partnership opportunities for Phase 3 development of otlertuzumab in CLL,” he said.
“With clinical proof-of-concept data demonstrating the efficacy and tolerability of otlertuzumab in previous combination studies, we believe that evidence of a clinical effect in PTCL could open up a promising new market opportunity for otlertuzumab in the treatment of T-cell malignancies where there is a significant need for safe and effective new treatments,” Stromatt added.
The company is also planning to file two Investigational New Drug (IND) applications in 2018 for two bispecific antibody candidates – APVO436 and APVO210.
APVO436 is being developed for acute myeloid leukemia and was designed to target the CD123 and CD3 proteins. CD123 is found in cells of several blood cancers, while CD3 is a key component of T-cells, which are vital for the immune system. APVO436 acts by engaging T-cells to kill tumor cells.
APVO210, being developed for autoimmune and inflammatory diseases, has a chimeric structure, built with a humanized anti-CD86 antibody fused with a modified form of IL-10. The therapy works by suppressing immune responses and is a potential therapy for disorders linked to deregulated immune systems.
“We believe that bispecifics represent the next frontier in antibody therapeutics and are encouraged by Aptevo’s rapid progress in this field,” Stromatt said.
“Importantly, the enhancements we have made to our next generation ADAPTIR platform are differentiated from other bispecific platforms, allowing us to assemble bispecific molecules that possess desired antibody-like features, including: efficient manufacturing properties, extended half-life, improved potency, increased stability and the potential for reduced toxicity,” he added.