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A Q&A with NewLink Genetics

Dec. 12, 2017

NewLink’s CEO describes his company’s focus on the IDO pathway in cancer immunotherapy.

One of the biggest themes in cancer immunotherapy research right now is trying to use multiple drugs in combination with each other. The goal is to make them work for more patients and in more types of cancers. Tumors unfortunately are multifaceted and have more than one means by which they naturally prevent the immune system from seeing them as foreign and attacking. Therefore, it might take a  combination of treatments that act on multiple pathways to have the largest effect.

One such pathway that is being actively pursued is called IDO. This has been a focus of the cancer immunotherapy research community lately because IDO drugs are now making it into the last stage of clinical testing in some cases. To help our readers learn more about it, we decided to go straight to the CEO of a company that is focused on IDO, NewLink Genetics (Nasdaq: NLNK). The Cancer Immunotherapy ETF (Nasdaq: CNCR) is pleased to support companies like NewLink that are working on novel approaches like IDO. To see a list of CNCR’s current holdings please click here.

Charles J. Link, Jr. MD, is NewLink’s Chief Executive Officer and Chief Scientific Officer. Dr. Link is a leading expert in the field of immunotherapy. Some of his many accolades include completing his residency and fellowship training in medical oncology at the National Cancer Institute, practicing oncology for 18 years, and co-founding NewLink in 1999. We posed 10 questions to him that we hope will better educate readers on the rationale behind IDO, how NewLink is utilizing this pathway with its drug indoximod in clinical trials, and what the company is looking forward to over the coming year.


textNewLink is focused on the IDO pathway in cancer. What is IDO and what role does it play in cancer immunotherapy?

The IDO pathway regulates immune response by suppressing T cell function and enabling local tumor immune escape. In other words, tumor cells may hide from the immune system by using the IDO pathway. Inhibition of the IDO pathway allows tumors to be “seen.” The potential role IDO inhibition has as a cancer immunotherapy is to be used in combination with therapies such as checkpoint inhibitors, chemotherapy or cancer vaccines. These therapies activate the immune response, with IDO “cloaking” the tumors. With indoximod, our IDO pathway inhibitor, the tumors are “uncloaked” such that the therapeutics can work to destroy the tumor cells.


textYour lead drug Indoximod impacts IDO in a different way than some competitor IDO inhibitors. How does it inhibit IDO specifically? Is there an advantage to this?

Indoximod has a differentiated mechanism of action (MOA) within the IDO pathway in that it acts directly on the immune cells and functions as a tryptophan mimetic rather than targeting the IDO enzyme directly. Whether there will be advantages to this mechanism has not yet been determined but the clinical results appear similar to data presented thus far with other IDO inhibitors. The unique mechanism may offer opportunities to explore different combinations and indications than the direct inhibitors, but this remains to be seen.



textYou have done a lot of work with Indoximod in melanoma and recently initiated a phase 3 clinical trial in combination with PD-1 inhibitors. How did you choose melanoma as the first main target for the drug?

The decision to pursue melanoma is based on three basic observations: First, melanoma is generally an immunotherapy responsive disease. Second, the current immunotherapy combination of PD-1 plus ipilimumab is limited due to toxicity. Finally, and most importantly, the most promising data with IDO, including indoximod, plus PD-1 therapy to date has been in advanced melanoma. These are the major factors why we are pursuing advanced melanoma as the initial indication, but we believe the opportunity for indoximod is much broader, including multiple malignancies.


textWhat timeline do you expect for the melanoma study? How long will it take to enroll and when do you estimate we might see initial data from it?

Our goal for the Phase 3 Pivotal trial of indoximod in combination with PD-1 inhibitors for patients with advanced melanoma is to be enrolled by the end of 2018. We will have a better idea of the timeline for once it is underway.


textYou recently announced a collaboration with AstraZeneca to test Indoximod in combination with the PD-L1 inhibitor durvalumab in pancreatic cancer. Why did NewLink and AstraZeneca choose pancreatic cancer?

Patients with pancreatic cancer represent one of the most significant unmet needs in oncology, and this indication is generally viewed as non-responsive to immunotherapy. However, the phase 2 data with indoximod plus standard of care show the potential to provide benefit in this difficult disease. This trial will compare the 4 drug regimen to the current standard of care in a patient population that has to date shown little benefit from immunotherapy.


textAre there any other cancer types you think might be well suited for IDO and PD-(L)1 combinations? What determines a promising target?

Indoximod’s differentiated mechanism may provide for unique clinical opportunities such as the one we are exploring in pancreatic cancer. However, the potential synergy of IDO inhibition with the checkpoint targets such as PD-1, PD-L1 and CTLA4 presents a wide array of potential opportunities in both hematologic malignancies and solid tumors.


textWhat types of improvement are you trying to make in future versions of this drug?

Our current version of indoximod, which is a new salt formulation, will be used in all new trials going forward. In addition to providing additional patent protection, this formulation has the potential for improved pharmacodynamics properties that may translate into advantages in efficacy and patient compliance. This formulation is now being used in our Phase 1b study of indoximod in combination with standard of care chemotherapy for patients with newly diagnosed Acute Myeloid Leukemia (AML).


textWhat are NewLink’s primary goals and milestones over the next twelve months?

Over the next twelve months we will be focused on the Phase 3 pivotal trial of indoximod in combination with PD-1 inhibitors for patients with advanced melanoma and our goal is to complete enrollment by the end of 2018. We are also looking forward to seeing the clinical program advance in other indications such as pancreatic cancer and AML and feel there are opportunities for additional collaborations which we will continue to work toward.



textWhere do you see the future of cancer care headed over the long term?

We believe immunotherapy is here to stay and will continue to evolve as discoveries lead to more targeted therapies and more varied combinations.


textWhat does shareholder support mean to you?

We are honored to have the support of long-time shareholders as well as newcomers to indoximod and NewLink. Their support allows us to continue the important work we are doing to bring new therapies to patients with cancer.


The Cancer Immunotherapy ETF is designed to invest in immunotherapy leaders like NewLink. We thank Dr. Link for his time, and wish everyone at the company all the best as they work to make IDO a cornerstone of combination therapy in the future.

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Opinions expressed are those of the author or Funds and are subject to change, are not intended to be a forecast of future events, a guarantee of future results, nor investment advice. Fund holdings and allocations are subject to change at any time and should not be considered a recommendation to buy or sell any security.


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