PIKAMAB announces the development of ADCC Therasight, a novel theragnostic product

Nov 12 2009

PIKAMAB, a stratified medicine biopharmaceutical company, announced today that it is developing ADCC Therasight^TM, a novel theragnostic product that can help guide the drug development process and patient treatment protocols for the cancer therapeutic antibodies that use ADCC (antibody-dependent cellular cytotoxicity) as the major mechanism of action.

ADCC Therasight uses PIKAMAB’s proprietary stratification method, 3x3 Matrix^TM, to measure the ADCC profile of patients by stratifying them into nine distinct groups. This involves two-dimensional stratification of the functional polymorphisms present in two key receptors, FcGR-3A and FcGR-2A. These receptors expressed on immune effector cells are responsible for binding to therapeutic antibodies and mediate killing of cancer cells by a process called ADCC.

Ronald Levy, M.D., at Stanford University School of Medicine provided clinical evidence that both FcGR-2A and FcGR-3A receptors dictate the therapeutic response rate of B-cell non-Hodgkin’s lymphoma (B-NHL) patients to rituximab treatment. This was based on a well defined, retrospective analysis of patient samples from B-NHL patients who were treated with rituximab as a monotherapy (no chemotherapy or radiation therapy involved) and followed for over 10 years. According to this study, ~4% of the patients were excellent responders with longer progression-free survival, ~30% were moderate responders, and ~65% were poor responders with shorter remissions.

Rituximab uses ADCC as the major mechanism of action in B-NHL indication. “Out of ~200 or so antibodies in the drug development pipeline, a significant number of antibodies are expected to use ADCC as a primary mechanism of action, and you can see this relatedness in sufficiently powered clinical studies when ADCC Therasight is used,” said Vijay Ramakrishnan, Ph.D., CEO of PIKAMAB.

ADCC Therasight could identify responders and non-responders prior to the administration of rituximab in B-NHL patients. The Company plans to develop a CLIA-certifiable test to enable physicians and payers to incorporate ADCC Therasight as part of their routine patient treatment protocols.

Not all patients treated with trastuzumab (indication: breast cancer) and cetuximab (indication: metastatic colorectal cancer) respond well even when the patients are selected based on their Her-2 expression profile or K-RAS genetic profile, respectively. This is because ADCC plays an equally important role in providing therapeutic response. “We can potentially treat more patients (from the currently ‘non-treatable’ group) when ADCC Therasight is used in conjunction with Her-2 and K-RAS tests,” explained Ramakrishnan.

Higher treatment costs aside, antibody therapies can have serious side effects and can lead to rare but life-threatening infections (example: progressive multifocal leukoencaphalopathy (PML) in rituximab-treated patients). “Why then expose non-responders to therapies that are not going to be effective? Instead these patients can be advised to have alternate treatment options that may work,” said Ramakrishnan.

“Development of customized, patient group-specific antibody therapies is a rational approach to achieving excellent therapeutic response rate in a great majority of patients. ADCC Therasight can be very useful in guiding the drug development process and patient treatment protocols of the antibody therapies that primarily use ADCC,” commented H. Michael Shepard, Ph.D., who led the discovery efforts of Herceptin^®, the first targeted therapy developed to treat breast cancer. He is a member of the Advisory Board of PIKAMAB.

PIKAMAB plans to partner with biopharma companies and integrate ADCC Therasight with their drug development programs. While an antibody candidate is still in early stages of clinical development, ADCC Therasight can determine if the antibody indeed uses ADCC as the major mechanism of action. “This information is quite powerful to have in advance as it can potentially reduce the clinical trial size and cost of the antibody development programs. More importantly, instead of generating clinical utility of a drug by ‘averaging’ for entire populations, ‘evidence-based utility’ in a single patient (group) can be obtained. This transformative approach provides a way to re-define the drug development and regulatory procedures,” said Ramakrishnan.

Source: PIKAMAB