Taking aim with innovation + experience

Expression of the membrane protein carbonic anhydrase XII (CAXII) is induced under hypoxic conditions in solid tumors. CAXII enzymatic activity is crucial for the survival and proliferation of cancer cells, resulting in tumor establishment, homeostasis, and metastasis. In addition, CAXII is required for Pgp-mediated resistance to chemotherapy. CAXII is overexpressed on various cancers such as renal, breast, colon, cervical and ovarian. Importantly, inhibition of CAXII activity has been shown to reduce tumor size, inhibit tumor migration, and to restore sensitivity to chemotherapy in preclinical models. Therefore, Talem has developed an antagonistic, fully human monoclonal antibody highly specific for CAXII. Talem focuses on the development of a lead candidate for the treatment of ovarian cancer due to the high unmet medical need, paucity of immunotherapeutic options, high recurrence rate, and frequent occurrence of resistance to chemotherapy.

Many solid tumors are poorly immunogenic as the binding of monoclonal antibodies to the tumor associated antigen (TAA) often fails to induce the required immune response for tumor cell killing. This renders immunotherapy less effective. Combining anti-TAA binding capability with anti-CD3 T cell engagement into one bispecific molecule enables the recruitment and activation of T cells to increase immunotherapy efficacy. The first generation of T cell engagers available on the market have a high affinity for CD3 and induce potent tumor cell killing, but also cause the release of high levels of cytokines, leading to severe side effects and a narrow therapeutic window. Talem has developed anti-CD3 Fabs specifically directed against CD3δε, which are expected to reduce cytokine release. These Fabs are available to combine with anti-TAA arms of potential partners for the generation of novel T cell engaging bi-, tri- and multi- specific molecules.

TATX-24: CD3δε Fabs

Format: CD3δε targeting fragment antigen-binding (Fab) arm for a bi- or multi-specific

Stage: Lead candidate

Mode of action: T cell engagement

Focused indication: Bi-, tri- and multi-specifics

Partner:

Partner:

Tropomyosin receptor kinase B (TrkB) is a receptor tyrosine kinase (TK) that is implicated in various solid tumors.
Ordinarily, TrkB expression is confined to the central nervous system where it is important for maintaining normal
brain function. Aberrant and overexpression of TrkB is implicated in various solid malignancies and associated with poor prognosis. Currently, therapeutic options for TrkB targeting are restricted to pan-Trk inhibitors, which lack specificity and cause side effects. The use of monoclonal
antibodies specifically binding TrkB for the intracellular delivery of toxic payloads (i.e. ADC) is anticipated to increase safety and efficacy of TrkB-directed cancer therapies. Additionally, large molecules, such as antibodies, do not readily cross the blood-brain-barrier, further reducing the risk of on-target side effects. Highly specific anti-TrkB internalizing antibodies are being developed to combine with ADC platform technologies of potential partners.

TATX-112: TrkB

Format: Monoclonal antibody for ADC-based therapeutics

Stage: Lead selection

Mode of action: Internalization for delivery of toxic payload into tumor cells

Indication: Solid tumors

Breast cancer (BC) accounts for 30% of all new female cancer cases each year. While there are good treatment options available, there are still hard to treat or unresponsive subtypes of BC, such as triple negative BC (TNBC). The (over)expression of the Tropomyosin kinase B (TrkB) and (over)activation of the TrkB signaling pathway play an important role in various solid malignancies, including BC, and are associated with poor prognosis. Preclinical studies have demonstrated that targeting the TrkB pathway can reduce BC cell growth and metastasis, but current TrkB-directed treatment options are not specific. Additionally, breast tumors are not highly immunogenic, rendering immunotherapy less effective. By combining Talem’s proprietary anti-TrkB antibody arms with proprietary anti-CD3δε T cell engaging antibody arms in a bispecific format, a novel and effective immunotherapeutic molecule against BC is being developed with the aim of improving therapeutic options.

TATX-200: TrkBxCD3 Bispecific Antibodies

Format: Bispecific antibody, T cell engager

Stage: Lead candidate

Mode of action: T cell engagement

Indication: Breast cancer (TNBC, HER2 neg.) and other solid tumors

One of Talem’s most advanced development programs, TATX-03 (anti-SARS-CoV-2 PolyTope), is a rationally designed, fully human, 4-antibody combinational therapy containing synergistic, potently neutralizing monoclonal antibodies against non-overlapping epitopes on SARS-CoV-2 spike trimer. Talem’s SARS-CoV-2 PolyTope therapy is designed to reduce mutagenic escape risk with an emphasis on efficacy for every patient, variant, and strain of SARS-CoV-2, and has been developed with the goal of sustainable efficacy as the virus evolves, combining broadly characterized, neutralizing and synergistic antibodies that exhibit diverse epitope coverage.

TATX-03: “PolyTope®”

Format: Multi-antibody combination Tx

Stage: IND enabling/drug product manufacturing complete

Target: SARS-CoV-2 and its variants

Activin receptor-like kinase 1 (ALK1), a member of the TGF-β receptor superfamily, is preferentially expressed on endothelial cells. Its ligands are BMP9 and BMP10. Impaired BMP9/ALK1 signaling is associated with various vascular pathologies such as diabetic retinopathy, diabetic kidney problems and pulmonary arterial hypertension (PAH); all chronic and hard to treat conditions. Enhancing signaling via the BMP9/ALK1 pathway has been demonstrated to reduce symptoms associated with PAH and to prevent hyperglycemia-induced vascular permeability in preclinical animal models. Enhancing ALK1-signaling by treatment with BMP9 carries the risk of side effects through interaction with its other cognate receptors. Therefore, Talem is developing agonist antibodies specific for ALK1 with the aim to generate a safe and effective therapeutic for these vascular pathologies.

TATX-21: ALK1

Format: Monoclonal antibody

Stage: Lead Candidate Selection

Mode of action: Stimulation of signaling (agonist)

Indications: Diabetic retinopathy and pulmonary arterial hypertension