Shawn Iadonato and his team at Kineta are hoping to play a big role in the next frontier of immuno-oncology by making cold tumors hot and by closing the big gap of unmet needs for patients. The Seattle, WA.-based translational research company has a robust pipeline, including its AViiD™ Screening Platform, and five novel drug and vaccine programs with a focus on chronic pain, infectious diseases, autoimmune diseases, and most recently, oncology. What makes Kineta’s cancer research unique is its proprietary screening platform to discover molecules which may have potential application in immuno-oncology.

Prior to founding Kineta, Iadonato co-founded and served as CSO of Illumigen Biosciences, Inc., where he led the successful discovery and preclinical development of the company’s anti-hepatitis C drug, which ultimately led to the sale of the Illumigen in December 2007 to Cubist Pharmaceuticals (now part of Merck & Co.). Before Illumigen, Iadonato managed the Human Genome Center at the University of Washington.

As part of a new industry series, WuXi AppTec Communications asked Iadonato his thoughts on Kineta’s new research on immuno-oncology, its potential, and what new developments are on the horizon for this exciting new therapeutic avenue for managing cancer.

WuXi: How is Kineta differentiated from other early stage biotech companies in the immuno-oncology space?

Shawn Iadonato: Kineta has a unique business model; and we have established a strong biodefense grant and contracting business with the National Institutes of Health (NIH). With pandemic viral outbreaks occurring on a regular basis, the NIH has supported the development of Kineta’s broad spectrum antiviral and vaccine adjuvant programs to directly address unmet needs in this area. These funds advance the development of our novel drug development programs and maximize the funds that we raise from private investment.

More recently, we have diversified funding for LHF-535, our antiviral for Lassa hemorrhagic fever drug, with an investment from the Wellcome Trust. The Wellcome Trust is based in London, manages an endowment of $26 billion, and is the second largest private funder of medical research in the world.

Our success in these biodefense areas has enabled Kineta to expand our pipeline into drug programs with much greater commercial potential. KCP-400 is our novel non-opioid for the treatment of chronic pain.  This program has received funding from the Department of Defense.

Most recently, we have leveraged our expertise in innate immunity to discover novel new immunotherapies for use in oncology. The medical need and commercial appeal for novel assets in immuno-oncology is tremendous. Additionally, partnering in this space was exceptional last year as eight of the top 20 upfront payments in licensing transactions were for a discovery stage immuno-oncology asset.

WuXi: How did Kineta get involved in this type of research?

Shawn Iadonato: We have a depth of experience in innate immunity and have developed the AViiD screening platform, our discovery engine. This high throughput screening platform identifies compounds that activate innate immune pathways that trigger anti-viral and anti-cancer responses. From this screening platform we initially discovered novel broad-spectrum anti-virals and vaccine adjuvants and expanded it to applications for immuno-oncology. It is very exciting to see the novel compounds that Kineta has identified through our screening platform, and the potential they have as life changing therapies for cancer patients.

WuXi: Do you see immunotherapy as the best new weapon against cancer?

Shawn Iadonato: Yes. There are several different types of immunotherapies in development, including small molecule immune modulators, checkpoint inhibitors (CI’s), cell therapies, oncolytic viruses, and vaccines that target all different types of cancer. Kineta is developing small molecule immune modulators. Each of these strategies has significant potential to change the way cancer is treated. Immuno-therapy provides the promise that we can move cancer to being treated as a chronic disease rather than just trying to extend survival.    

WuXi: Can you describe Kineta’s immunotherapy research and how the company’s approach compares to other immunotherapies?

Shawn Iadonato: Tumors have many strategies of immune evasion as the tumor environment is immunosuppressive. As a result, tumor cells are not recognized as foreign and tumor cell death is immunologically silent. Kineta’s immuno-oncology program is focused on developing small molecule compounds that exploit novel drug targets in innate immunity. We are focused on RIG-I like Receptors, including RIG-I, MDA5 and other targets.

Kineta’s immuno-oncology drugs are unique and have demonstrated in preclinical models that they can break tumor tolerance, cause immunogenic cell death, and elicit neo-antigen responses. They can turn a ‘cold tumor hot’ through specific molecular mechanisms and work in synergy with other immunotherapies like checkpoint inhibitors.

Our approach is further differentiated from other immunotherapies as they are small molecule drugs that can enable rapid drug development and may be dosed orally or systemically.

WuXi: What types of cancer respond best to immunotherapy?

Shawn Iadonato: We are at an early stage in the evolution of immunotherapies, and the industry is rapidly trying to fully understand their potential in cancer. We see very encouraging efficacy with checkpoint inhibitors in most solid tumors, however there remains an opportunity to improve efficacy through combination therapy. As a result, collaborations evaluating CI’s in combination with other immuno-therapies has been a key focus in both clinical studies and partnering. Clinical development will continue to accelerate and evolve to find the optimal combination for different solid tumor cancers.

For hematologic malignancies, there is a tremendous amount of excitement around cell based therapies. CAR-T cell therapies are being developed by several companies and have shown great potential in blood based cancers.  However, some of these therapies have also demonstrated serious adverse events as well. Further safety studies will need to be conducted to fully evaluate the risk-to-benefit of these exciting therapies.

WuXi: How do you see the cancer immunotherapy field evolving over the next five years and how will Kineta play a role?

Shawn Iadonato: Checkpoint inhibitors have solidified their position as a cornerstone immuno-therapy for many solid tumor cancers.  GlobalData projects that sales of CI’s will increase to $10 billion in 2019 and $24 billion by 2024.  CI’s are a tremendous advancement in therapy as there remains a significant treatment gap and opportunity to improve survival for cancer patients. The manufacturers of these products are exploring numerous new therapies being used in combination. CI’s are most effective in high mutational burden cancers or when the tumor is ’hot.’  New strategies are needed to turn the ’cold tumor hot‘ and enable CI’s to be more effective and improve survival for a larger percentage of cancer patients. Kineta’s strategy is to turn the cold tumor hot through these specific molecular mechanisms.  Our drugs elicit immunogenic cell death in tumor cells and activate a signaling cascade that stimulates neo-antigen tumor responses. They can act synergistically with CI’s to enhance their efficacy and improve survival and offer the promise of being the next generation of immuno-therapies.

WuXi: What role will combination therapies play in cancer immunotherapy?

Shawn Iadonato: Immunotherapies such as the checkpoint inhibitors like Keytruda, Opdivo, and Tecentriq that are currently on the market have greatly improved survival for many patients with cancer. This is a great start, however, they have only been effective in up to 20-to-40% of cancer patients, and there remains a significant unmet medical need. We believe that checkpoint inhibitors will continue to be a cornerstone therapy and combination therapy will improve the overall efficacy and survival.

WuXi: Are partnerships key to Kineta’s business development plan?

Shawn Iadonato: Yes, Kineta is actively seeking a partnership with a larger pharmaceutical company to advance the development of our immuno-oncology program. We believe that our approach to immuno-oncology will complement other treatments, particularly checkpoint inhibitors. As a result, we believe the best development path forward for Kineta is to work in collaboration with another company focused on immuno-oncology.

WuXi: How can the government help speed the drug development process?

Shawn Iadonato: In immuno-oncology, government programs like the Cancer Moonshot Initiative can provide tremendous support to our industry to fund and accelerate early-stage research and clinical studies. Kineta’s antiviral programs have been largely supported through funds from the National Institutes of Health. The NIH’s support has enabled Kineta to advance the development of novel broad spectrum antivirals and vaccine adjuvants.  Similarly, the cancer moonshot initiative is a $1 billion initiative to jumpstart cancer research and development.  In 2017, there is $755 million in mandatory funds available for new cancer-related research activities at both the NIH and the Food and Drug Administration. In cancer immunotherapy and combination therapy specifically, this initiative will work to extend the early successes of cancer immunotherapy by supporting basic research to increase understanding of how the immune system can be used to modify cancer cells and their activities. Additionally, the initiative aims to develop new combination therapies, and can provide much needed support to early-stage biotech companies like Kineta.