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To win the fight against cancer, we need to combine precision nutrition with advances in biology and machine learning.


While cancer treatments have made great strides in the past decade with the advent of immunotherapies and antibody drug conjugates, the oncology toolkit itself – with the trifold approach of drugs, surgery and radiotherapy – hasn’t added a novel intervention in a century. At Faeth, not only are we pioneering precision nutrition as the fourth pillar for cancer care, but we are also advancing an integrated approach that combines advances in oncology and works in tandem with the current standard of care.


Trying to develop nutrition-based interventions without genomics is like shooting in the dark. But focusing solely on drugging genetic mutations, without taking into account the whole metabolic picture, will result in a fractured attack against cancer, allowing the tumor to survive and continue to spread.


Faeth’s mission is to treat every cancer, every patient. And to succeed, we’ll need to incorporate what we’ve learned from the genomic revolution into how we hijack cancer metabolism to starve tumors.


Nobel Prize-winning biochemist Otto Warburg first hypothesized almost 100 years ago that removing glucose from the diet would be the key to killing tumors, because of how cancer cells produce energy. While Warburg and others failed to show that glucose control, in isolation, could be a cancer-fighting “golden gun,” his important discovery about cancer metabolism cracked open the door for precision nutrition to become a key tool in treating cancer.


However, pursuing these metabolic insights was largely abandoned during the genomic revolution. About a decade ago, the availability and affordability of sequencing technology made it easier for oncologists to incorporate these tools into their practice. The idea was to find a mutation and then drug that mutation – enforcing the primacy of therapeutics as the third pillar in cancer care. Genomics provided a deeper understanding of cancer not as a simple disease but as an extremely heterogeneous collection of thousands of diseases that share some of the same symptoms, including unchecked cell spread and proliferation.


But if Warburg’s understanding of cancer as a purely metabolic disease was incorrect, we have overcorrected by thinking of cancer only as a genetic disease.


With genomics, researchers identified dozens of ways that tumors speed up their growth and evade the immune system, which in turn have spawned countless targeted therapies. But the varying success of these drugs have demonstrated that just understanding a cancer's genotype isn’t enough to eradicate it; the truth is more complex. And in trying to answer why some drugs appear to work against themselves, or how the body adapts resistance mechanisms, some world-class cancer researchers, including Faeth’s co-founders, have come full-circle back to Warburg – that precision nutrition cannot be ignored in the fight against cancer.


Cancer is indeed heavily influenced by genetics, but these genetic mutations cause changes in cellular metabolism, which in turn influences a tumor’s reliance on specific nutrients.


The support for precision nutrition as the fourth pillar of cancer care is far from being merely theoretical. We have an overwhelming amount of preclinical data from some of the leading cancer researchers in the U.S and the U.K. that offers convincing evidence to this effect. Two of Faeth’s co-founders, Marcus DaSilva Goncalves and Lew Cantley, authored a 2022 paper in Nature Reviews Cancer that highlights the breadth and depth of precision nutrition interventions that have been validated in preclinical models. These interventions are numerous, precise, and reproducible. They consider the organ of origin, tumor genotype, and drug response.


For example, Faeth co-founder and Chief Scientific Officer Oliver Maddocks found in two separate papers published in Nature in 2013 and 2017 that depleting serine and glycine, two non-essential amino acids, can help increase average survival time by 30-200% in certain mouse models of cancer.


It is time, however, to move out of the lab and into the clinic. Exquisitely tailored combinations of precision nutrition with therapeutics, surgery and radiotherapy can change the arc of our battle against cancer.


Today, Faeth examines the entire genome of cancer cells to look for metabolic signatures. With our machine learning platform, metabOS, we examine large groups of cancer patients, grouped by genomic sequencing and drug response data, to look for prevailing nutrient vulnerabilities within a specific segment of that indication. We then confirm individually before enrolling patients in our trials that each patient has that metabolic trait.


But by capitalizing on the power of genomics, we expect in the future to be able to develop truly personalized precision nutrition interventions. By looking at each patient’s individual RNA sequencing data, we can go beyond broad treatment groups based on one or two genetic signals to nutrient control tailored to individual genetic signatures.


The future of cancer care will be built on the successful integration of these two fields. Faeth’s researchers aim to show that starving tumors of precise nutrients – based on genetics – can effectively control and eliminate them.




Updated: Jan 19

Ignoring nutrition is no longer an option



About two and a half years ago, a venture capitalist named Vinod Khosla asked me about working with him. I said no thanks. Venture capital wasn’t interesting to me. I like two things: building from the ground up and science. Venture provides exposure to the latter but is not hands-on enough when it comes to the former. So instead, Vinod introduced me to some scientists who he was thinking about supporting. What I learned changed my life.


On a rainy day last July, I met them at Weill Cornell in New York City. It was a collection of some of the greatest living cancer scientists. Together, they told me about how nutrition was overlooked in the fight against cancer, and if we didn’t design precision nutrition interventions and evaluate them with the same care as we do drugs, it would be a disaster with very real human consequences.


The data alone was worth the trip from San Francisco. It was mind-blowing. The magnitude and simplicity of the data and story was overwhelming – nutrition shaped our bodies and the environment that cancer drugs entered into. That environment itself could be reconfigured to be toxic to tumors but also to make traditional drugs better – more effective and with fewer side effects. Starve tumors using precision diets, all while making traditional drugs better and safer.


Since that day, I knew we had to build Faeth and that the work we do is not just important but a moral imperative. Faeth is on a mission to see whether we can translate and scale the metabolic dimension of cancer for the millions of patients in need.


 

What can we learn from other diseases?


We know that nutrition is an incredibly powerful tool to treat disease. For many diseases like hypertension, diabetes, and inborn errors of metabolism, it’s the first step in management or even reversal (s/o to my former colleagues at Virta Health for showing the way in diabetes). But in cancer, the best advice we can give patients is “eat clean” or “keep your weight up.” That’s crazy! Furthermore, newly published research indicates that traditional diet recommendations for cancer often can COUNTERACT standard of care treatments. At Faeth, we are here to fix this.


In 2021, we hit a new scientific milestone when patients with a rare disease called ATTR had their genome edited. We have the technology to edit your DNA, but if you have cancer, “keep your weight up” is the best we can do?!?! That feels incongruous to us at Faeth. Ask any oncologist and they will say: “What can I change about my diet?” is one of the first questions patients ask when diagnosed with cancer. But the same oncologist will also tell you they don’t have any evidence-based nutrition interventions to prescribe. In short, oncologists know that their advice is imperfect, but it’s the best they have. Faeth is here to help change that.



Introducing the new foundation of cancer care


At Faeth, we are here to add to the patient and oncologist’s arsenal and transform cancer outcomes. The cancer treatment universe is currently comprised of four potential interventions:


  • Pillar #1 - Surgery

  • Pillar #2 - Radiotherapy (X-rays)

  • Pillar #3 - Small molecules (e.g. chemo, targeted therapies, etc.)

  • Pillar #4 - Biologics (e.g. immunotherapy, antibodies, etc.)


We can do better than this. My co-founders have already shown us the path. A growing mountain of data suggests that not only can precisely targeted nutritional interventions be as or more efficacious than traditional interventions but that precision cancer nutrition could also make traditional interventions – like the four pillars above – safer and more effective. Welcome to the new foundation of cancer treatment.




Evidence-Based, Patient-Centric Cancer Treatment


Take a look at this graph showing cell growth in one of the hardest to treat cancers (it’s what killed Steve Jobs and Ruth Bader Ginsburg): Pancreatic cancer. It’s tough to treat, even in the lab. Faeth’s precisely targeted intervention actually performs much better than chemo in a head-to-head setting. We are all about pairing drugs with diets, and you can see from the graph below how effective our treatment could be when paired with chemo in pancreatic cancer. Faeth was formed to translate and scale the decade-plus of preclinical data my cofounders have amassed and we are beginning early-stage trials at some of the best cancer centers in America to evaluate our approach in a variety of cancers: Pancreatic, colorectal, endometrial, and clear cell ovarian cancer. If you know someone who could be a patient, please send them to us! A link to all our clinical trials is right here.





 

Why now?


The idea driving Faeth - precisely engineered diets to starve tumors - is one that has been around for decades. Ever hear of the old adage that sugar feeds your tumor? While there have been lots of hypotheses about diets that can “cure cancer,” the fact is that all of these attempts have failed on two counts: first they aren’t scientifically rigorous, and second they don’t recognize that cancer is not one disease.


The first point is pretty obvious, and I’ll leave someone else to talk about it, but the second point is important. Cancer isn’t a monolith. It’s actually thousands of different diseases with shared symptomology - unchecked cell proliferation and spread.


Over the last twenty years, we have begun to understand that a KRAS mutated colorectal tumor is going to behave differently than a P13K mutated colorectal tumor (if you aren’t a scientist, KRAS and P13K are oncogenes - genes that are mutated in cancer). These diseases have to be thought of differently and any precision nutrition intervention has to account for this. In fact, any intervention has to consider not only the tumor genotype but the organ from which cancer originates and the standard of care therapy. Basically, we have to develop nutritional interventions like we develop cancer drugs. With precision.


The recognition of the startling heterogeneity of cancer, the advent of precision genomics, the explosion of machine learning and computational models in biology, greater availability of organoid models, and a deeper level of RNA sequencing data, were all required for a company like Faeth to be built and actually stand a chance of success. Warburg and his early 1900s kin simply didn’t have the tools to do what needed to be done to actually address cancer with precision nutrition.



How does it work?


Faeth is like three companies in one: we develop drugs, build software and create food. This isn’t because we like complexity. We don’t. There was just no other way. We’re building the kind of cancer treatment company that patients need. A company that can develop drugs, create real, fresh-food diets designed to potentiate those drugs, ship them to your doorstep, and build software with registered dieticians behind it that ensures patients have the help and support they need to succeed.


For the patient, the experience is seamless. Our dietitians are the main point of contact throughout the treatment journey but all of Faeth’s clinicians, scientists, and chefs are working tirelessly on your behalf behind the scenes.


Every Cancer, Every Patient


At Faeth, we believe that precision nutrition is the fifth pillar of cancer care that can unlock greater outcomes. If a precision nutrition approach utilizing cancer genotype, organ of origin, and standard of care treatment is going to be the way forward, then how do we then develop the potentially thousands of interventions that will be needed to help bend the curve across all cancer indications. The solution is in our machine learning discovery platform: MetaBOS.


Using machine learning, we have begun to analyze large data sets of metabolomic data in cancer. That has unearthed learnings that we have begun to validate in the lab. In fact, some of the programs in our pipeline today were discovered as a result of MetaBOS. MetaBOS is what makes our preclinical process scalable and gives us the ability to know where to look in the infinite complexity of cellular biology. When our approach works, we will be ready to scale interventions to all those in need, globally.



How do we make it happen?


Great people and devotion to our mission and values. That’s it. Period. If you are excited about working at a mission-focused company with a once-in-a-lifetime team and an awesome group of investors in a totally remote setting, email me or take a look at our open roles.