Pangea Biomed developed ENLIGHT – the world’s most advanced multi-cancer, multi-therapy response predictor. By utilizing machine learning and deep RNA analysis, the company is mapping tumor molecular signatures to dynamically and adaptively personalize cancer care for a healthier world. Pangea aims to bring effective precision oncology to cancer patients, improve oncology drug development and empower oncologists to successfully treat patients. Pulse 2.0 interviewed Pangea Biomed CTO Ranit Aharonov to learn more.
Ranit Aharonov’s Background
Before joining Pangea, Aharonov was the global manager of Project Debater at IBM, the first AI system capable of successfully debating humans on complex topics.
“Project Debater successfully engaged in a live debate with a human debate champion, Mr. Harish Natarajan, in a public demonstration in February 2019 in San Francisco, attracting highly positive worldwide attention. Project Debater was IBM’s third grand challenge after Deep Blue (chess) and Watson (Jeopardy). Eventually, the technology behind Project Debater will help people reason by providing compelling, evidence-based arguments and limiting the influence of emotion, bias, or ambiguity,” said Aharonov. “Going even further back, I led R&D efforts for Rosetta Genomics in the early 2000s, when molecular diagnostics was in its infancy. Rosetta Genomics was a pioneer in discovering new microRNAs and using them for cancer diagnostics. As VP of R&D, I took part in transforming the company from a small startup in a villa near Jerusalem to a company that launched three diagnostic projects, combining advanced algorithms with lab developments, and offered them through a CLIA lab we established.”
Aharonov joined Pangea after almost ten years of researching NLP since, ultimately, nothing compares to hearing you change someone’s life.
“I am extremely proud of the advances we have made and are still making with our ENLIGHT platform. Every day brings new challenges, new successes, and an enormous amount of satisfaction. As the CTO of Pangea Biomed, I have led the development of the company’s technology to make precision oncology accessible to all cancer patients,” Aharonov continued. “I spearheaded the improvement of Pangea’s underlying AI, creating a successful cancer response predictor with the potential to save lives. Pangea’s tech also drives collaborations with pharma companies and diagnostic activities. Additionally, I have co-led two publications demonstrating the potential of ENLIGHT to change the standard of care for oncology patients. At Pangea, we are transforming the way traditional precision cancer care works.”
Favorite Memory
What has been Aharonov’s favorite memory working for Pangea so far? “Receiving an email from a patient’s husband who received a treatment based on an ENLIGHT report. That email came after they found out she was responding to her treatment. His words of gratitude simply make all the hard work worth it and gives so much energy and motivation to continue,” reflected Aharonov.
Challenges Faced
What are some of the challenges Aharonov faced in building the company and has the current macroeconomic climate affected the company? “In the current macroeconomic climate, we see a general slowdown in investments in the biotech field. Investors seem particularly cautious of making high-risk-high-reward investments that may take some time to show returns. However, such times also present great opportunities,” Aharonov acknowledged. “Over-abundance of venture capital makes it hard to distinguish companies with truly superior technology and good management from ones that lack these but got heavily funded nevertheless. When the going gets tougher, these differences become clearly evident, and savvy investors know that backing the right companies at such times can create stronger competitive advantages and allow these companies to fast forward once conditions change for the better. In addition to seeking out such discerning investors, we are also working hard to obtain non-dilutive funding from government funds that prefer high-risk projects with potential high gain. Such grants can significantly de-risk investments for institutional investors.”
Core Products
What are Pangea’s core products and features? “Pangea has developed the world’s most advanced multi-cancer response predictor, ENLIGHT, which is scalable to all cancer types and all targeted and immuno-oncology drugs. The technology increases the number of patients who can benefit from precision oncology by 5x. As the world’s first and only multi-cancer response predictor scalable to all cancer types and all targeted and immune checkpoint blockade (ICB) oncology drugs, the ENLIGHT platform goes beyond standard biomarkers to surface relevant biological insight, improve oncology drug development, and empower oncologists to treat patients with success. ENLIGHT is able to do this through two main modules: the Genetic Interactions (GI) Engine and the Prediction Engine. The GI Engine processes multiple big-data repositories to infer which gene pairs are likely to be related through certain functional relationships called genetic interactions. Each gene pair is assigned an interaction score, which ranks how likely it is to represent a clinically-relevant genetic interaction. The output of the GI Engine is a set of genetic interaction maps showing genes connected by high-scoring genetic interactions. These maps are generated both on a pan-cancer level and for specific cancer indications,” Aharonov explained. “The Prediction Engine combines the genetic interaction maps produced by the GI Engine with information on drugs, biological pathways, and patient-specific multi-omics data to derive personalized predictions of response to cancer. Based on these predictions, ENLIGHT screens and ranks dozens of potential treatments for each patient, complementing standard genomic matching biomarkers. As one platform, ENLIGHT enables actionable treatment nomination for most patients, identification of novel drug targets, identification of drug combinations that optimize clinical outcomes, improved biomarkers for drug trials, and drug indication expansion. In June 2022, Pangea revealed its ENLIGHT-DP framework. This framework opens the door to precision oncology for individuals in geographies and situations where next-generation sequencing is unavailable due to lack of resources, time, or tissue.”
Evolution Of Pangea’s Technology
How has Pangea’s technology evolved since launching? “Pangea was founded in 2018 when we first started building the ENLIGHT platform. We combined machine learning and deep RNA analysis to map tumor molecular signatures to dynamically and adaptively personalize cancer care for a healthier world. Our goal was and still is, to bring effective precision oncology to cancer patients, improve oncology drug development and empower oncologists to treat patients successfully. Since 2018, we have started working with pharmaceutical companies to extend their biomarker capabilities, advance their understanding of drug MOAs, and improve their drug development and lifecycle management,” Aharonov noted. “Our research partnerships with renowned medical institutions and hospitals have also flourished. We’ve validated the ENLIGHT approach and platform broadly and have published important new research in leading journals, including Cell, Med, Science Advances, Cancer Cell, Journal for ImmunoTherapy of Cancer, and Nature Communications. But perhaps our most exciting advancement is our latest breakthrough, ENLIGHT-DP, for digital pathology. With this technology, we have revolutionized the measurement of gene expression, a process that is traditionally time-consuming and costly. Through advanced deep learning techniques, we can extract gene expression data directly from standard tumor pathology slides (H&E slides), which are essentially available for every cancer patient. This simplifies and expedites the process significantly and will enable quick and affordable response prediction at scale. Our validations so far have shown that this technology achieves predictive power comparable to using the traditional gene expression measurements and even comparable to methods that require extensive datasets for training.”
Significant Milestones
What have been some of Pangea’s most significant milestones? Aharonov cited the following:
— In June 2022, Pangea revealed ENLIGHT-DP, which is a framework that will truly democratize precision oncology, as it uses standard pathology slides, eliminating the need for expensive and time-consuming genetic sequencing. And this opens the door to precision oncology for individuals in geographies and situations where next-generation sequencing is unavailable.
— In December 2022, two peer-reviewed studies on the efficacy of ENLIGHT were published. In JITC, a case report revealed the success of an ENLIGHT-matched treatment for a woman with rare liver cancer. In Med, a study Aharonov co-led with Pangea co-founder and current Chief of the NCI’s Cancer Data Science Lab Eytan Ruppin, revealed that ENLIGHT demonstrably enhances the ability to predict therapeutic response across multiple cancer types from the bulk tumor transcriptome. And for personalized oncology, ENLIGHT-matched treatments had 2.6x higher odds of response than unmatched treatments. For clinical trial design, ENLIGHT demonstrated the potential to enhance clinical trial success for immunotherapies and other monoclonal antibodies by accurately excluding non-responders.
— Pangea recently announced a research collaboration with Onconova Therapeutics, a clinical-stage biopharmaceutical company, to leverage ENLIGHT to identify biomarkers of response to Onconova’s proprietary investigational product candidate rigosertib.
Customer Success Stories
Can you share any specific customer success stories? “In one extraordinary case, a patient was diagnosed with a rare type of liver cancer that resisted treatment and spread to her lungs and abdomen. Comprehensive molecular profiling revealed no ‘actionable mutations,’ and the patient was referred to Pangea. Within less than a year, the patient had a complete response to the therapy matched by ENLIGHT and is now back to normal life, without a trace of the disease in subsequent imaging,” Aharonov shared.
Funding/Revenue
When I asked Aharonov about funding/revenue, she replied: “Pangea generates revenue by partnering with global biotech and pharma companies, helping them to develop better drugs and find the patients most likely to benefit from these drugs. Also in December, we announced additional funding to scale ENLIGHT, bringing the company’s total funding to over $12 million.”
Differentiation From The Competition
What differentiates Pangea from its competition? “The Precision Oncology field is highly competitive and dynamic. But ENLIGHT stands out in several respects. First, current practices can match patients to treatments about 15% of the time, while our technology does this 90% of the time! In addition, most current methods only cover a limited range of cancer types and treatments, i.e., they are built for a specific diagnostic or predictive question. In contrast, ENLIGHT covers an extremely wide range of cancer types and treatments. ENLIGHT is also unique because it is highly extensible to new modalities, which means we can “ride the wave” of new technologies in the field,” Aharonov revealed. “To add to that, unlike the standard path, our approach does not depend on clinical response data from the drugs analyzed, so it’s applicable to new and experimental drugs just as well as to old and established ones. This is important both in the clinic and for pharma companies. Finally, our new ENLIGHT-DP product in development will enable an affordable treatment-matching solution.”
Future Company Goals
What are some of Pangea’s future company goals? “An immense gap exists between the investment and innovation going into precision oncology drug development and the number of patients who are actually benefiting from these drugs. ENLIGHT’s potential to bridge this gap provides hope to many cancer patients who are currently just out of reach of already-existing, truly life-changing therapies,” Aharonov concluded. “ENLIGHT is already being leveraged by leading clinicians and researchers from Massachusetts General Hospital, the National Cancer Institute, the University of California San Diego, and the largest hospital in Israel: Sheba Hospital. Pangea is focused on ensuring its ENLIGHT platform continues to provide the highest efficacy to improve patients’ lives. Determined to uncover better, scalable drugs and treatments, Pangea works closely with pharmaceutical companies to identify key mediators of response and resistance to treatment. In one of the largest precision oncology initiatives to date, Pangea’s ENLIGHT platform will be tested soon in a prospective setting. The trial, which should open later this year, aims to recruit hundreds of patients annually, across several years and multiple cancer types.”
