What can we learn from the survivors

AIMM’s focus is to interrogate the B-cell antibody response of cancer survivors to identify novel and innovative treatments for yet unserved or underserved cancer patients.

Utilizing our AIMSelect and AIMProve platforms, AIMM has developed a strong pipeline of novel drug candidates that bind new and unexpected targets and epitopes. Our ability to identify functional antibodies and their novel targets is facilitated by a well optimized process that includes target identification and confirmation as well as an understanding of fundamental immunology.

Our lead asset is AT1412 (see illustration below), an antibody that binds to a unique epitope on CD9. AT1412 allows CD9 tumor targeting without the induction of platelet aggregation. AIMM is advancing the CD9 lead program through preclinical development, with the goal of filing a Clinical Trial Application in Q4 2020 and treating the first patients in early 2021.

We also have several antibody candidates in lead optimization, and we expect to select a second antibody for advancement into preclinical development by the end of 2020 (i.e. AT1413, AT1636). AIMM is exploring collaborations that may further the development of some of these pipeline antibodies, such as its CD3- bispecific, ADC and CAR-T candidates.

Importantly, we have a robust discovery engine and are aggressively working to fuel our pipeline with (natural) human antibodies  targeting novel epitopes.

Discovery
Lead optimization
Preclinical development
Phase 1
CD9
CD43s
Undisclosed
CTA Q4 2020

AT1412

Source

AT1412 was isolated from a stage 4 melanoma patient with brain metastasis who was successfully treated with ex-vivo autologous T-cells. The patient’s blood was obtained 6 years after having undergone the successful treatment, and the patient is still tumor-free (now, 13 years later) despite having this aggressive cancer (Verdegaal, Osanto. Cancer Immunol Immunother, 2011).

Product

AIMM is advancing the CD9 lead program through preclinical development and will file a Clinical Trial Application (CTA) in Q4 2020, aiming to start treating patients in the first half of 2021. The data package supports the clinical evaluation of AT1412 in B-ALL and CD9+ solid tumors (e.g. melanoma, gastric, breast, esophagael) as a monotherapy and in combination with immune checkpoint inhibitors (anti-PD1).

Target

One single tumor-specific antibody, AT1412, was identified from a melanoma survivor. AT1412 targets a unique, previously unidentified epitope on CD9 that allows CD9 tumor targeting without inducing platelet aggregation. Solid tumors (including melanoma, breast, gastric and esophageal) and B-ALL express elevated levels of CD9, which is correlated with worse patient survival. AT1412 induces antibody-dependent cell-cytotoxicity (ADCC) and antibody-dependent cell phagocytosis by macrophages (ADCP), in addition to mediating T-cell infiltration into the tumor. The anti-tumor activity of AT1412 is further enhanced by combination with immune checkpoint inhibitors (anti-PD1). In vivo, AT1412 has elicited tumor rejection through enhanced T-cell and macrophage infiltration and induction of IFN𝛾-response cytokines. In preclinical safety studies, the safety profile of AT1412 was confirmed.

AT1413

Source

AT1413 was isolated from an M5 AML patient that underwent allograft stem cell transplantation and that has been in remission for 8 years now. B-cells were obtained 3 years after undergoing treatment. (see also our publications)

Product

The tumor-specific targeting of AT1413 enables enhanced potency by formatting into a CD3-bispecific, ADC or CAR-T. Lead optimization will be finalized to support the initiation of IND-enabling studies in 2021.

Target

AT1413 specifically recognizes a specific sialylated epitope on CD43. AT1413 binds to all AML (all subtypes), leukemic stem cells and MDS samples tested and a subset of melanoma and breast cancer. AT1413 induces antibody- dependent cell-cytotoxicity (ADCC) and complement- induced cytotoxicity (CDC). In vivo, AT1413 induced tumor cell death of AML cells. AT1413 has been recently shown to also bind to solid tumors, such as melanoma and breast cancer. Its efficacy can be further potentiated by formatting the antibody as a CD3-bispecifc antibody, CD3-AT1413, which is capable of inducing tumor rejection in in vivo models of AML and melanoma.

AT1636

Source

AT1636 was isolated from a male Lynch syndrome patient (MSH6 gene mutation) that was diagnosed with stage 4 colon carcinoma with liver metastases. After treatment with chemotherapy in combination with Avastin, blood was obtained 9 years later, the patient is still in remission now 13 years later.

Product

The co-expression of the undisclosed target and the glyco-modifying enzyme is found on many epithelial cancers. The tumor- specific targeting of AT1636 enables enhanced potency by formatting as a CD3-bispecific, ADC or CAR-T. Lead optimization will be finalized to support the initiation of IND-enabling studies in 2021.

Target

AT1636 was isolated by virtue of its tumor-specific binding to colon carcinoma cell lines. AT1636 binds to a post-translationally (glycol-epitope) modified truncated protein that is specifically expressed on epithelial cancer cells. Cancer-specific aberrant expression of the enzyme
is responsible for the glyco-modification leading to dual targets for the specific binding of AT1636 to tumor cells. Despite an immune-suppressive environment, AT1636 is capable of killing cancerous cells. This effect can be further potentiated when engrafting AT1636 as a CD3-bispecific antibody.