PharmaShots Interview: Indapta’s Mark Frohlich Shares Insights on the $50M Series A Financing

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PharmaShots Interview: Indapta’s Mark Frohlich Shares Insights on the $50M Series A Financing

In an interview with PharmaShots, Mark Frohlich, CEO at Indapta Therapeutics shared his views on the closing of $50M A financing and how it will advance its cell therapy drug development


  • The company closes $50M A financing, co-led by RA Capital Management, LP, Vertex Ventures HC, and Bayer AG with Mark Frohlich appointed as M.D., CEO and also joined the board of directors
  • The funding will support the company’s allogeneic NK cell platform for IND and clinical trials. The platform includes isolation and expansion of a subset of NK cells known as G-NK cells with increased potency
  • This interview gives a glimpse at the advancement of Indapta’s G-NK cell therapy to treat multiple cancers

Smriti: Please tell our readers about G-NK cell therapy.

Mark Frohlich: G-NK (pronounced G minus NK) cells are present in some people who have been infected with a common virus called cytomegalovirus (CMV). These cells are thought to arise from conventional NK cells, being naturally engineered by the immune system to fight viral infection. The cells undergo epigenetic modification, such that a variety of genes are persistently up or down modulated. For example, the FcεRIγ intracellular signaling adapter is deficient, and all signaling downstream of CD16 that binds antibodies instead occurs through the CD3-zeta protein. As a result of these changes, the cells are extremely potent against cancer or virally infected cells. Compared to conventional NK (cNK) cells, when G-NK cells recognized target cells that are coated with an antibody, they secrete more cytotoxic enzymes and effector cytokines and kill the cells more effectively. (This is termed antibody-dependent cell-mediated cytotoxicity or ADCC). The cells also persist longer than cNK cells and are more effective in killing target cells that down up-regulate HLA-E, one mechanism that tumor cells use to try to evade immune killing.

Indapta has developed a method to grow large numbers of G-NK cells for the treatment of cancer. Specifically, in collaboration with a network of blood banks, we identify individuals who have a significant number of G-NK cells in their peripheral blood. We perform large volume apheresis to collect donor immune cells. Using a proprietary method that further activates and preferentially expands the G-NK cells, we produce large numbers of high purity G-NK cells. These cells are then frozen down to generate dozens of “off-the-shelf” doses for cancer patients. Because genetic engineering is not required, the manufacturing process is streamlined, with a favorable cost of goods.


Smriti: Can you tell us about the multiple types of cancer indications that G-NK cell therapy can treat?

Mark Frohlich: G-NK cells have the potential to treat any cancer. Based on the encouraging early clinical data seen with other NK cell therapies and the highly potent ADCC activity of G-NK cells, we are planning to first test Indapta’s G-NK cells in both lymphoma and multiple myeloma patients. Our clinical trial will test single and multiple doses of G-NK cells alone, and then in combination with the approved monoclonal antibodies rituximab and daratuzumab in the lymphoma and myeloma cohorts, respectively. We are also interested in using G-NK cells to treat acute myelogenous leukemia (AML), as well as a variety of solid tumors.


Smriti: How is G-NK cell therapy better than conventional NK cells therapies?

Mark Frohlich: When compared to cNK cells, G-NK cells have more potent ADCC, secrete more cytokines when recognizing antibody-coated targets, kill target cells more efficiently, persist longer, express lower levels of CD38 (and thereby avoid being eliminated when used in combination with a CD38 targeting antibody-like daratumumab), and are more potent against HLA-E expressing cells.


Smriti: Can we discuss the preclinical data which demonstrated the efficacy of G-NK cell therapy?

Mark Frohlich: Indapta has tested G-NK cells in a number of preclinical models, including challenging lymphoma and multiple myeloma models where NK cells alone have minimal activity. In these models, when G-NK cells are used in combination with therapeutic monoclonal antibodies like rituximab or daratuzumab, they are able to provide durable tumor regression with long-term survival. In the same models, cNK cells provide only transient tumor responses.


Smriti: Enlist out Indapta’s different partnerships and how it’s going to support the development of this therapy.

Mark Frohlich: Lonza is currently both an investor and our good manufacturing process (GMP) contract manufacturing partner. We have optimized our GMP process and performed a technology transfer to Lonza. We are currently working with them to generate the manufacturing data required to file our investigational new drug application with the FDA, as well as produce the G-NK cells for our clinical trial. The Myeloma Investment Fund of the Multiple Myeloma Research Foundation (MMRF) is also an investor, and we look forward to drawing on the MMRF’s deep experience in clinical and translational research in multiple myeloma to inform our strategy in multiple myeloma. The NIH has awarded Indapta with two grants, a Small Business Technology Transfer (STTR) grant in collaboration with Stanford University, and a Small Business Innovation Research (SBIR) grant in collaboration with UCSF.


Smriti: Give a glimpse of the company’s $50 million Series A financing and enlist out the names who led the fundings.

Mark Frohlich: The lead investors in our Series A financing were RA Capital, Vertex Ventures, and Leaps by Bayer. We are very encouraged by the endorsement of this investor syndicate with deep experience in immuno-oncology and cell therapy.


Smriti: What’s your plan for the advancement of this therapy?

Mark Frohlich: Our plan is to demonstrate clinical proof-of-concept in lymphoma and multiple myeloma in combination with approved therapeutic monoclonal antibodies. If we can demonstrate clinically meaningful responses to the therapy with sufficient durability, we then would plan on a single-arm registration trial under the accelerated approval regulatory pathway. In subsequent studies, we would plan to move the therapy earlier in the treatment paradigm, for example, where the therapeutic antibodies rituximab and daratumumab are used as part of combination therapy early in the course of metastatic disease.


Smriti: Give an overview of Indapta’s pipeline.

Mark Frohlich: We are considering additional clinical trials in other hematologic malignancies like AML. Our strategy in solid tumors may involve combinations with approved therapeutic monoclonal antibodies, like cetuximab or herceptin. We will be conducting preclinical studies in head and neck cancer with Stanford University later this year under an STTR grant. We are also exploring the possibility of genetic engineering of G-NK cells to deliver payloads to augment the survival of the cells in vivo, to modulate the tumor microenvironment, and/or to directly target cancer cells by addition of a chimeric antigen receptor.

Source: Medicine Net

About Author:

Mark Frohlich is the CEO of Indapta Therapeutics. He is a medical oncologist with more than 20 years of industry experience in cell therapy drug development that will support the company through this next phase of its development. Dr. Frohlich earned a B.S. in electrical engineering and economics from Yale College and an M.D. from Harvard Medical School

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Senior Editor

Senior Editor at PharmaShots. She is curious and very passionate about recent updates and developments in the life sciences industry. She covers Biopharma, MedTech, and Digital health segments along with different reports at PharmaShots.

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