Preclinical toxicology and pharmacology evaluation of a newTNFR2 antagonistic monoclonal antibody for CTCL therapy

PROJECT SUMMARYCancer has killed over 600,000 people in US in 2020. The cost for healthcare and society is unbearable: becauseof cancer, $180B healthcare expenditure and $134B lost productivity are recorded every year. This is happeningdespite recent advancements in therapy and the emergence of an ever expanding array of new therapeutics forthe over 1.8M new cancer patients every year. Indeed, because of the multitude and redundancy of mechanismscontributing to cancer growth, therapies are often ineffective. Several components should be targeted at thesame time in order to maximize therapy outcome. However, this is particular hard to attain because of 1) thestriking variability among cancers and the limited number of cancer specific targets 2) the ability of cancer cellsto orchestrate a microenvironment of healthy tissue and cells around them, that promote cancer growth andtherapy resistance. Boston Immune Technologies and Therapeutics (BITT) is developing BITT-1492, able totarget both cancer cells and their microenvironment. BITT-1492 is an antagonist antibody against TNFR2 – areceptor highly expressed in cancer tissue and immune suppressive cells in the microenvironment, where itmediates pro-survival signaling. Thanks to BITT’s proprietary antibody design platform, BITT-1492 is the firstand only antibody able to dominantly shut down TNFR2 signaling. Due to selective expression and key role ofTNFR2 for a variety of cancers and tumor microenvironment cells, BITT-1492 will find application in the therapyof several cancers, starting with Cutaneous T cell Lymphoma (CTCL), where TNFR2 is known to act as anextremely potent oncogene. BITT has already completed extensive pre-clinical validation for BITT-1492,demonstrating potent activity in CTCL, colon and ovarian cancers. In the proposed Fast-Track project, BITT willcomplete a pre-clinical toxicology and pharmacology assessment of BITT-1492 to obtain relevant data for anInvestigational New Drug (IND) application. This will be accomplished by performing, in line with ICH guidelines,an exploratory small-scale toxicology study to be carried out in Phase I, that will demonstrate the safety of useof BITT-1492 for a wider IND-enabling toxicology and pharmacokinetic studies in Phase II. As part of the PhaseIIBITT will also test the suitability of BITT-1492 production process for cGMP standard compliance. At the end ofthe SBIR project, BITT will be ready to advance BITT-1492 to clinical testing for which a combination of VentureCapital seed funds and SBIR PhaseIIb are expected to be leveraged. The successful completion of this projectand initial clinical testing evidence will help to secure the already expressed interest of pharmaceuticalcompanies with whom BITT will engage to complete late-stage clinical testing and launch BITT-1492 intointernational markets.