Clinical-stage and oncology-focused biopharmaceutical company CytomX Therapeutics, pioneering a novel class of investigational antibody therapeutics based on its Probody™ therapeutic technology platform, has acquired drug-conjugate linker-toxin and CD3-based bispecific technologies from Agensys, an affiliate of Astellas Pharma.
Under the terms of the agreement, CytomX will pay Astellas a one-time, up-front payment.
“The clinical progress we reported throughout 2018 provided initial proof of concept for our Probody therapeutic platform. This transaction with Astellas provides us with novel payloads and CD3 binding moieties for our next wave of potent anti-cancer agents that leverage our technology, including Probody drug conjugates and Probody T-cell engaging bispecifics,” explained W. Michael Kavanaugh, M.D. chief scientific officer and head of research and non-clinical development at CytomX.
Pipeline
Probody therapeutics developed by CytomX are designed to exploit unique conditions of the tumor microenvironment to more effectively localize antibody binding and activity while limiting activity in healthy tissues.
The company and its partners have four programs in the clinic, includes cancer immunotherapies against clinically-validated targets, including a PD-L1-targeting Probody therapeutic (CX-072), a PD-1-targeting Probody therapeutic (CX-188) and a CTLA-4-targeting Probody therapeutic (BMS-986249) being developed in collaboration with partnered with Bristol Myers Squibb.
The pipeline also includes first-in-class Probody-drug conjugates against highly attractive targets including a CD166-targeting Probody-drug conjugate wholly owned by CytomX (CX-2009), and a CD71-targeting Probody drug conjugate partnered with AbbVie (CX-2029).
CD166 and CD71 are among cancer targets that are considered to be inaccessible to conventional antibody-drug conjugates due to their presence on many healthy tissues.
In addition to its wholly owned programs, CytomX has strategic collaborations with AbbVie, Amgen, Bristol-Myers Squibb and ImmunoGen, Inc.
PROCLAIM-072 Trial
In November 2018 CytomX presented clinical translational data from PROCLAIM-072, an ongoing Phase I/II, open-label, dose-finding trial evaluating CX-072, a Probody therapeutic targeting PD-L1, in a poster at the 33rd Annual Meeting of The Society for Immunotherapy of Cancer (SITC) being held in Washington DC, USA.[1]
The PROCLAIM trial (Probody Clinical Assessment In Man) is an international umbrella program designed to evaluate CytomX’s Probody therapeutics. The first trial in this program, PROCLAIM-CX-072, evaluates CX-072 as monotherapy and in combination with ipilimumab (Yervoy®; Bristol-Myers Squibb) or vemurafenib (Zelboraf®; Genentech/Roche ) in patients with metastatic or locally advanced unresectable solid tumors or lymphomas.
As part of the trial, participating patients received escalating doses of CX-072 from 0.3 mg/kg to 30 mg/kg. Biopsies were obtained from a subset of PROCLAIM-CX-072 patients during screening and at either 3-5 days after the first dose or after 4-6 weeks of CX-072 therapy. The presence of protease activity, CX-072 cleavage and activation, and measures of biological activity were assessed within tumors.
Results showed that protease activity was detected in the majority of patient biopsy samples (15 of 18 (83%)). Further, CX-072 was cleaved and activated within tumors, with the total amount of activated CX-072 increasing with dose. Doses of ≥ 3 mg/kg of CX-072 were estimated to achieve ≥ 98% PD-L1 target occupancy in patient tumors and attained concentrations that are associated with efficacy in a preclinical model. 7 of 12 evaluable patient biopsies showed an increase in tumor infiltration of CD8+ T cells, an activity consistent with the inhibition of the PD-1/PD-L1 signaling pathway.
“The preliminary data provide additional proof-of concept for the Probody platform and build upon the clinical data we have presented to date showing that CX-072 appears to be performing as designed in patients,” Kavanaugh noted
“These findings confirm that CX-072 is unmasked and activated and has biological activity in patient tumors while remaining predominantly masked and intact in circulation. This is another important step in understanding the full potential of our novel platform,” he concluded.
Reference
[1] PROCLAIM-CX-072: A Trial to Find Safe and Active Doses of an Investigational Drug CX-072 for Patients With Solid Tumors or Lymphomas – NCT03013491
