On May 15, 2020 Molecular Partners AG (SIX: MOLN), a clinical-stage biotech company that is developing a new class of custom-built protein therapeutics known as DARPin therapeutics, reported the presentation of preclinical data from three of the company’s programs at the American Academy for Cancer Research (AACR) (Free AACR Whitepaper) Virtual Annual Meeting II, June 22-24, 2020 (Press release, Molecular Partners, MAY 15, 2020, View Source [SID1234558171]).

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Data to be presented on MP0317 (FAP x CD40) include in vitro and in vivo experiments which show that MP0317 displays significant tumor-localized immune activation without systemic toxicity seen with anti-CD40 antibody administration. In human B cells and dendritic cells, MP0317 was found to activate the CD40 pathway solely in the presence of fibroblast activation protein (FAP)-positive cells, confirming its strict dependence on FAP-mediated crosslinking. In a mouse model, a mouse-specific FAP x CD40 DARPin molecule was found to substantially inhibit the progression of FAP-positive tumors without showing any of the toxicities seen with administration of a mouse CD40 antibody. FAP is a tumor-associated antigen abundantly expressed in many solid tumors, which Molecular Partners is leveraging to co-locate MP0317 to its target tissues.

Data to be presented on the peptide-MHC DARPin program review the creation of bispecific DARPin T cell engager proteins that bind with high specificity to a HLA-A2: SLL peptide-MHC complex. The constructed DARPin proteins were observed to effectively activate T cells at a range of concentrations and to carry out highly targeted cell killing exclusively on those cells that were positive for NY-ESO-1, from which the SLL peptide is derived. This demonstrates proof-of-concept for the ability of DARPin therapeutics to effectively drug peptide-MHC complexes.

Thirdly, a poster to be presented on AMG 506 / MP0310 (FAP x 4-1BB) describes pharmacokinetic and pharmacodynamic research to establish the optimal dose range for this novel tumor-localized immune agonist. AMG 506 / MP0310 is now in a Phase 1 clinical study.

The details are as follows:

MP0317: An oral presentation of MP0317 titled "A tumor-targeted CD40 agonistic DARPin molecule leading to antitumor activity with limited systemic toxicity" will take place during the minisymposium entitled "Immunomodulatory Agents and Interventions" and will be accessible here.
Peptide-MHC DARPin: "Application of the DARPin technology for specific targeting of tumor-associated MHC class I: peptide complexes", Poster No. 690
AMG 506 / MP0310: "Selection of first-in-human clinical dose range for the tumor-targeted 4-1BB agonist MP0310 (AMG 506) using a pharmacokinetic/pharmacodynamics modeling approach", Poster No. 2273
Following their presentation, the posters will be made available on the corresponding section of the Molecular Partners website.

Financial Calendar
August 26, 2020 Publication of Half-year Results 2020 (unaudited)
October 29, 2020 Interim Management Statement Q3 2020
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About DARPin Therapeutics
DARPin therapeutics are a new class of custom-built protein therapeutics based on natural ankyrin repeat proteins that open a new dimension of multi-functionality and multi-target specificity in drug design. A single DARPin candidate can engage more than five targets within a single molecule, and its flexible architecture and small size offer benefits over conventional monoclonal antibodies or other currently available protein therapeutics. DARPin therapeutics have been clinically validated through to registration via the development of abicipar, Molecular Partners’ most advanced DARPin drug candidate. The DARPin platform is a fast and cost-effective drug discovery engine, producing drug candidates with optimized properties for development and very high production yields. DARPin is a registered trademark owned by Molecular Partners AG.