“Identifying Personalized Treatment Recommendations for Gastro-Intestinal Cancers“

“Identifying Personalized Treatment Recommendations for Gastro-Intestinal Cancers“ (Laura Towart and Nahuel Villegas, PhD) [#131] Brad Power February 12, 2025 “We have our own variant-calling software, which identifies the genetic alterations that are driving that patient's unique cancer. We can select up to twenty genetic alterations. We engineer them in fruit flies.

We use fruit flies as an avatar. We do this for many reasons, but one of the most important is that the flies are so malleable, and we’re able to engineer a significant number of alterations to make these truly complex tumors in an animal.

Then we expand the fly population to hundreds of thousands of animals, and we use this, what we call an ‘avatar army’, for screening thousands of drugs and drug combinations. So, at the outset, we’ve screened everything that's ever been approved by the FDA alone, and then in combinations, and then we see combinations that will rescue the fly, and then we make a human treatment recommendation.

Now we've generated this large dataset, and we incorporate machine learning algorithms and the dataset to be able to have rapid, personalized recommendations without the need for the modeling in the animal.” – Laura Towart Meeting Summary Cancer is extremely complex. It is driven by multiple genetic mutations.

Current treatments often target only a single mutation, which can lead to resistance as cancer evolves. Personalized medicine is improving treatment effectiveness with tools like genomic profiling, but we still have a long way to go to fully tailor treatments to the genetic complexity of each patient.

This is one of the reasons you see high failure rates and resistance to the "standard of care" therapies, and why it is essential to assess your tumor and identify your unique, complex tumor network. Each tumor signature may respond to a different therapy. Laura Towart and Nahuel Villegas are uniquely qualified to lead a discussion about how you can more fully personalize your cancer treatment.

Laura Towart is the founder and CEO of Vivan Therapeutics, a company with a ground breaking personalized approach to cancer and rare disease developed at Mt Sinai Medical Center. Laura became passionate about personalized medicine during her PhD studies at Weill Cornell Graduate School for Medical Sciences/Memorial Sloan Kettering Cancer Center.

Since then she has been actively involved in translational advances in medicine. In 2008 she co-founded Celmatix, and helped build a next- generation women’s health company leveraging big-data and genomics. Laura has a strong personal link to colon cancer as it sadly claimed her mother and grandmother and affected other family members and friends.

She is committed to the identification of new therapies that are tailored to each patient and advocates for patients and their access to these therapies. Dr. Nahuel Villegas is the Chief Scientific Officer of Vivan Therapeutics.

other and grandmother and affected other family members and friends. She is committed to the identification of new therapies that are tailored to each patient and advocates for patients and their access to these therapies. Dr. Nahuel Villegas is the Chief Scientific Officer of Vivan Therapeutics. He has a background in genetics, stem cells, and cancer biology.

He obtained his PhD in biological sciences from the University of La Plata (Argentina). Afterwards, he trained in embryonic stem cells and developmental biology at the MRC Centre for Regenerative Medicine (University of Edinburgh, UK), and in cancer research at the Institute for Neuroscience (CSIC-University Miguel Hernandez, Spain). Dr.

“Identifying Personalized Treatment Recommendations for Gastro-Intestinal Cancers“ (Laura Towart and Nahuel Villegas, PhD) [#131] the fruit fly Drosophila melanogaster to study druggable conserved oncogenic targets.

His work bridges basic and translational science, combining cancer genetic analysis with in vivo high- throughput drug discovery strategies aimed at finding novel pharmacological anticancer cocktails for personalized therapy. The mission of Vivan Therapeutics is to offer patients personalized cancer treatment options.

They coordinate sequencing of your tumor biopsy and blood sample and their variant calling software identifies your unique constellation. They then use their TuMatch software, which leverages their proprietary data set and AI/machine learning, to enable rapid, personalized cancer treatment guidance.

They assist you with treatment direction from identifying the most effective standard of care options, identifying potential clinical trial options, and providing novel options when standard of care is no longer effective. Why might you want to pursue innovative tests, such as animal models, to personalize your cancer treatment?

●Identify unique drug combinations tailored to your specific tumor genetic profile ●Find potential treatments beyond standard care, including non-cancer drugs that might be effective ●Screen thousands of drug combinations to find the most promising therapies ●Reduce toxic side effects by finding more targeted, precise treatment approaches How can you use data from animals and AI models to identify drugs for your unique cancer?

●A testing service based on an animal model of your cancer can replicate your tumor and test the effectiveness of different drugs in vivo. There are different animal models, we use fruit flies to model the patient tumor, which offer several advantages over mice, zebrafish and other animal models, creating a personalized, living representation (“twin”, “avatar”) of your disease.

This “avatar” can allow systematic drug screening across thousands of drug combinations, especially novel drug combinations, including non- cancer drugs that might be effective.

zebrafish and other animal models, creating a personalized, living representation (“twin”, “avatar”) of your disease. This “avatar” can allow systematic drug screening across thousands of drug combinations, especially novel drug combinations, including non- cancer drugs that might be effective.

●Since the platform collects and analyzes data from millions of animals and thousands of drugs and drug combinations, AI&ML techniques can be implemented to generate accurate predictions leading to more efficient personalized treatment recommendations. What are the key challenges in accessing and integrating animal model services into your cancer care?

●Time: It takes six months to build an animal model. Many patients approach us when they have already run out of therapeutic alternatives and it is already too late to identify a personalized treatment on time, due to the time-consuming process of building and screening avatars.

“Identifying Personalized Treatment Recommendations for Gastro-Intestinal Cancers“ (Laura Towart and Nahuel Villegas, PhD) [#131] ●Cost: It costs $20,000+ to generate the fully tailored therapies, even though much cheaper than other strategies, still could be a barrier for some patients.

●Regulatory: Conservative medical review boards make it difficult to approve personalized treatments from novel tests. ●Clinical trial limitations : Traditional clinical trial designs struggle with personalized, one-of-a-kind treatments, making it hard to validate efficacy. Who should consider this approach of animal models and AI? ●You have GI cancer: colorectal, pancreatic, etc.

●You have a brain tumor ●You have a rare cancer with no standard treatment options. ●Standard of care, traditional treatments have been ineffective. ●You have been recently diagnosed, allowing time for modeling and screening. ●You are cancer free, but the rate of recurrence of your tumor type is high. ●Your cancer is not extremely aggressive, allowing time for modeling and screening.

●You are searching for novel drug combinations, including non-cancer drugs that might be effective. How can you learn more about animal models and AI for personalizing your treatment?

●Attend patient-focused webinars and conferences discussing personalized cancer treatments using animal models and AI ●Explore the Vivan website, review their published case studies, particularly those from Mount Sinai Medical Center ●Contact Laura Towart (laura@vivantx.com) or Nahuel Villegas (nahuel@vivantx.

com) to schedule a consultation and discuss the process for accessing Vivan Therapeutics' services ●See other discussions we have had on animal models (organoids) and personalizing your cancer treatments: ○"Organoids Guide Treatment Decisions" (Payel Chatterjee, SEngine) [#13] ○"Using Functional Profiling to Predict Drug Response" (Dr.

Robert Nagourney) [#30] ○“Identifying the Most Effective Treatment on the Tumor Rather than Trying It Out on the Patient” (Dr.

treatments: ○"Organoids Guide Treatment Decisions" (Payel Chatterjee, SEngine) [#13] ○"Using Functional Profiling to Predict Drug Response" (Dr. Robert Nagourney) [#30] ○“Identifying the Most Effective Treatment on the Tumor Rather than Trying It Out on the Patient” (Dr.

Chris Apfel) [#84] ○“Finding Personalized Cancer Treatments Beyond the Standard through a Unique Test” (Travera) [#77] The information and opinions expressed on this website or platform, or during discussions and presentations (both verbal and written) are not intended as health care recommendations or medical advice by Cancer Patient Lab, its principals, presenters, participants, or representatives for any medical treatment, product, or course of action.

You should always consult a doctor about your specific situation before pursuing any health care program, treatment, product or other course of action that might affect your health.

“Identifying Personalized Treatment Recommendations for Gastro-Intestinal Cancers“ (Laura Towart and Nahuel Villegas, PhD) [#131]

“Identifying Personalized Treatment Recommendations for Gastro-Intestinal Cancers“ (Laura Towart and Nahuel Villegas, PhD) [#131] Meeting Notes KEYWORDS Precision medicine, cancer treatment, personalized therapy, fruit flies, machine learning, tumor sequencing, genetic alterations, drug screening, oncology, patient care, clinical trials, AI models, genetic profiling, novel combinations, patient outcomes.

SPEAKERS Laura Towart (48%), Nahuel Villegas (28%), Brad Power (14%), Bill Paseman (5%), Video (3%), Tony Magliocco (1%), Yara Alrokh (1%), Hilary Elkin (1%) CHAT CONTRIBUTORS Hilary Elkin, Allen Morris, David Plunkett, Yara Alrokh, Zakaria, Bill Paseman SUMMARY Brad Power introduced Laura Towart and Nahuel Villegas from Vivan Therapeutics, who discussed their precision medicine methodology for cancer treatment.

Vivan Therapeutics uses machine learning and a large proprietary dataset of tumor signatures to identify personalized cancer treatments. They create fruit fly avatars to screen drug combinations, testing thousands of therapies.

A case study highlighted a patient with colorectal cancer who responded well to a novel combination of trametinib and a bisphosphonate, extending life very significantly, with stable disease for 11 months. The service costs $25,000 for personalized drug screening and $5,859 for treatment recommendations. They have modeled 45 patients, mostly with colorectal and pancreatic cancers.

As a case report, a patient with nine genetic alterations responded well to a novel combination of a MEK inhibitor and a bisphosphonate. Target and nontarget lesions displayed a strong response and remained stable for 11 months. OUTLINE Introductions ●Laura Towart introduced herself as the founder and CEO of Vivan Therapeutics, which uses technology developed at Mount Sinai Medical Center.