Innovation with a purpose — Early discovery employee spotlight

March 24, 2023
About the Author

Shilpi Khare, Ph.D. is the Associate Director of Biology at Mirati Therapeutics. She serves as the non-clinical pharmacology representative on the SOS1 program, as well as early-stage discovery programs, and leads a team of talented scientists on preclinical translational research focused on informing clinical strategy.

Q: Title and quick explanation of what you do at Mirati?

A: I am an Associate Director of Biology in the Research Group here at Mirati. I serve as the non-clinical pharmacology representative on the SOS1 program, as well as early-stage discovery programs including SOS1/2, and am responsible for supporting lead candidate characterization and selection for IND-enabling studies. I lead a team of incredibly talented scientists on preclinical translational research focused on informing clinical strategy.

Q: What made you pursue a career as a scientist?

A: For me, it was a fortuitous blend of both nature and nurture. Although I grew up in a family of passionate academic chemists that fostered my interest in science, I’ve always been very curious about biology and the cosmos from an early age. In kindergarten, I enjoyed playing the electronic board game “Operation” with my older sister and was awed by the complexity of the human body. A few years later, I learned about the solar system and was fascinated by astronomy and the Big Bang Theory. I’d map out the constellations at night with my telescope and read all about the planets in my Britannica Encyclopedia set. I was amazed to discover that Earth was the only planet suitable for life due to its 78% Nitrogen:21% Oxygen atmospheric composition. Why are these elements so important for life to exist? How does a chemical imbalance lead to disease? These were a couple of the questions that led me to pursue my education in science, particularly Biochemistry and Molecular Biology, and further apply my knowledge as a scientist to discover cures for human ailments. Years later, I remain inquisitive and enthusiastic as a drug hunter, working together with my colleagues to discover therapies that can improve the lives of cancer patients and their loved ones.

Q: Why Mirati? In all the companies pursuing science, what made you pick this one?

A: From my own research experience in a variety of disease indications, what I quickly learned is that both drug (target) selectivity and drug resistance are reoccurring problems in the field. Undesirable side effects lead to poor patient compliance and eventually lower response rates for diseases with unmet medical needs. I was interested in pursuing an opportunity in precision medicine, where I could apply my skillset towards the discovery of a targeted lung cancer therapy, to honor my family and others affected by this top cause of cancer death worldwide. It seemed to be the “right time” in my career, and Mirati, a company at the forefront of precision medicine, was the “right place”. I was ready to make significant contributions towards bringing best-in-class novel targeted therapies to cancer patients in need.

Q: Describe the journey that brought you to Mirati?

A: Following my academic training at UCLA, I completed a postdoctoral fellowship right down the street at Novartis and gained expertise in genomics-based target discovery for the treatment of neglected infectious diseases. Most notably, our team’s work led to the discovery of a first-in-class parasite-selective proteasome inhibitor LXE408 that is currently being evaluated in Phase II clinical trials for visceral leishmaniasis. I then went on to pursue roles as a Group Leader/Principal Research Scientist in both academic and pharmaceutical research settings, where I focused my efforts on early-stage target-based drug discovery in the fields of women’s health, metabolic and GI disorders. Although my experience was in multiple disease areas, a common theme connecting all of them is drug resistance, a problem constantly being tackled in the oncology field and one that piqued my interest. After a few years of research under my belt, I came to a point in my career where I was ready to dive deeper into preclinical work and focus on delivering safe and efficacious therapies directly to patients. Simultaneously, I came to a point in my personal life where my father-in-law was diagnosed with Stage IV lung cancer and felt the urgent need to shift gears to cancer research to honor my family, which has lost three dear fathers to this horrible disease. I became hyper-focused on finding an opportunity to apply my knowledge towards the discovery of a novel cancer drug for the treatment of lung cancer and applied for an opening in the research group led by oncology experts Jake Haling, Pete Olson, and Jamie Christensen at Mirati. I was thrilled to join their team in April 2021, ready to work relentlessly to bring a SOS1 inhibitor to the clinic.

Q: During your time at Mirati have you witnessed a significant growth in the science, innovation, and capabilities? Feel free to elaborate.

A: I joined the team in April 2021 and since then, have observed significant growth in the translational research workstreams focused on expanding the potential of our precision oncology therapies. We have developed a pipeline of targeted medications and are exploring additional rational combination strategies to make a broader impact and also combat drug resistance in patients with non-small cell lung cancer, colorectal cancer, pancreatic cancer, and mesothelioma. I am excited to contribute to these efforts that will bring transformative therapies to a greater number of patients in the clinic.

Q: As a scientist it can take years for you to see results. What keeps you motivated when you know that out of 10-15 drugs created, only 1 may go into a patient?

A: This statistic keeps me both motivated and dedicated to conducting high quality translational research that will positively impact patients. My relentless pursuit of finding cures for patients would normally lead to many ideas which I am thrilled to pursue and bring to fruition even though I know only a handful of those will actually be accepted by stakeholders. As drug discovery scientists, we maximize our efforts to conduct streamlined experiments that specifically address the question at hand. We get excited by positive results, learn from unexpected results, and push forward to answer new questions that inevitably arise. We are constantly challenged and refining our skillset to both discover and deliver the safest, most efficacious therapy to patients to improve their quality and length of lives. Even if it is only one drug that goes into a patient, this was the result of years of hard work by hundreds of scientists, and we are making a difference. Any benefit to humanity as a whole is clearly a win, and I am hopeful and 100% committed to this noble cause.

Q: As you reflect on all the great work you have contributed at Mirati, what do you think are the key ingredients to your success?

A: It was an honor to be selected to be a part of the amazing research group here. I was provided the opportunity and the facility to discover new therapies for cancer patients in need and I am collaborating with an incredible team of scientists for a common goal. Our team’s success is the result of our collective dedication to one another, our patients, and the cutting-edge and highly impactful science we work on. We build fruitful partnerships with our colleagues in the drug discovery, DMPK, CMC, clinical pharmacology, and project management groups to create first-in-class therapies. We are nimble, creative, filled with passion and grit, and ready to take on any challenge that comes our way.

Q: What is your personal perspective of the importance of sustaining a culture of inclusion to strengthen, inspire and cultivate a culture of belonging at Mirati?

A: Creating a culture of inclusion is a top priority for me as a group leader and female scientist. I firmly believe that, in order to support all of our colleagues from various backgrounds, it is imperative to acknowledge, embrace and celebrate each person’s individuality and to create opportunities for each of us to succeed in our common goal of bringing transformative therapies to cancer patient with unmet medical needs. I personally find it critical to generate open dialogues in order to better gauge the current state of team culture and to learn how I can proactively implement fair and sustainable solutions to maximize employee visibility and engagement. Furthermore, with an AIM employee recognition system in place and various forums to spotlight diverse experiences (such as this!), I believe that we will continue to encourage and inspire one another to work relentlessly towards achieving Mirati goals.

Q: What do you think is unique about Mirati, relative to other Biopharma companies with respect to cancer targets we pick and approaches we take to tackle these diseases?

A: From my experience, Mirati’s approach to cancer discovery is highly patient focused with an attitude of as fast as possible. Our top-notch research leadership team is determined and very keen on selecting cancer targets that are novel, selective, and significantly impactful with regards to the breadth and number of patients that can positively be impacted. We pursue targets that can combine rationally with our current assets for the quickest path to patients or ones that directly address emerging drug resistance and/or significant unmet medical needs. New targets are well researched and presented at a forum of key stakeholders from both drug discovery and research teams, with input and rigorous discussion encouraged to maximize our efforts on the fastest timeline possible. The highly collaborative team efforts have culminated in four IND applications and an NDA submission with subsequent accelerated approval of KRAZATI™, all in the last 15 months. We are creating a better life for cancer patients who are resistant to CPI therapy or harbor MTAP deletions, KRASG12C and KRASG12D mutations, and there is no other team I’d rather work on to bring precision oncology therapies to the clinic.