“Identifying the Most Effective Treatment on the Tumor Rather than Trying It Out on the Patient”

“Identifying the Most Effective Treatment on the Tumor Rather than Trying It Out on the Patient” (Dr.

Chris Apfel) [#84] Brad Power January 31, 2024 “What really drove me was my personal experience and the realization that, while we often like to believe at major institutions that the future is here now, the reality is, if one of you is affected, and you have been, that we often are still living in the past.

We're not leveraging all the possibilities and technologies that are currently in development.” – Chris Apfel “If a patient gets treated according to what demonstrates sensitivity (a test's ability to designate an individual as positive), or if we are avoiding resistance for this patient, the likelihood … is that you double your odds to have a tumor response.

” – Chris Apfel Meeting Summary As an advanced cancer patient you want a wide range of treatment options and a good idea whether you will respond to any treatment. As we have heard in our discussions with Tony Letai, Robert Nagourney, First Ascent, Travera, and SEngine, "functional testing" directly tests cancer drugs on your live cancer cells to see what the drugs do.

It is a way to identify treatment options and predict which treatment is going to be best for you. It bases your decisions on trying it, not on theorizing about what might work. Chris Apfel, MD, PhD, MBA is uniquely qualified to talk about the latest practices in functional testing.

He was a successful anesthesiologist, intensivist, and clinical researcher whose work has been cited over 20,000 times by other doctors and whose clinical prediction model has several million hits on Google and is now standard of care in many institutions, including Stanford. He was surprised that genomic testing wasn’t the answer when his father was diagnosed with late-stage lung cancer.

Moreover, his father, who had taken care of his wife when she struggled with ovarian cancer, refused therapy unless he could tell his father with great certainty that a treatment would work. The experiences of his parents drove Dr. Apfel to search for more effective approaches for cancer patients.

He left his faculty position as a practicing clinician at UCSF, got an MBA from Wharton to complement his scientific and medical experience, and, together with his wife, Dr. Brigitte Apfel, also a physician, founded SageMedic Corp. and developed the SAGE Oncotest™ with the latest in functional testing technology. How is the SAGE Oncotest similar to other functional tests?

The reason why functional testing has the power to make a prediction on what will work is because it's done on live tissue. Like other functional tests, the SAGE Oncotest requires live tumor tissue or “malignant fluids” (excess fluids with cancer cells that accumulate in the body).

Patients who show low or no evidence of disease, or have hard-to-reach tumors, will have trouble getting enough fresh cancer cells.

uires live tumor tissue or “malignant fluids” (excess fluids with cancer cells that accumulate in the body). Patients who show low or no evidence of disease, or have hard-to-reach tumors, will have trouble getting enough fresh cancer cells.

SageMedic and others apply the candidate drugs at various doses, including in amounts greater than normally found in the body, such that if there is no response at that level, that drug can be ruled out, and if the tumor cells die, then that drug is a good candidate. How is the SAGE Oncotest different from other functional tests?

“Identifying the Most Effective Treatment on the Tumor Rather than Trying It Out on the Patient” (Dr. Chris Apfel) [#84] Rather than older methods of growing organoids (cancer cells multiplied in the lab) for functional testing, SageMedic has developed a process and platform to create hundreds of “microtumors” (copies of the tumor tissue) in their lab in a day.

They can then test dozens of drugs and drug combinations with results in 7 to 10 days. Other tests using older organoid technology are accurate if you get a result, but often you don't get a result, and it can take months.

Rather than looking at single cells as in some other functional tests, SageMedic’s microtumors retain the tumor microenvironment and heterogeneity of the biopsy and the three dimensionality that is emphasized these days to understand not just the cancer cells but what is going on around them.

Single cell functional tests claim results in two days, but these results haven’t been proven in clinical trials. How can you access the SAGE Oncotest and work with SageMedic? ●You can request the test for your care, especially if you have solid tumors that cannot be surgically removed or have recurred and have failed first- or second-line therapies.

●You can collaborate in pilot validation or tissue donation studies.

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 the Most Effective Treatment on the Tumor Rather than Trying It Out on the Patient” (Dr.

Chris Apfel) [#84] Meeting Notes SUMMARY KEYWORDS patient, tumor, oncologist, drugs, tissue, assay, dose, functional testing, therapies, biopsy, test, treatments, cells, question, chris, developed, sensitivity, dose response curves, number, results SPEAKERS Chris Apfel (72%), Brad Power (9%), Glenn Sabin (5%), Arra Yerganian (4%), Amit Gattani (4%), Brian McCloskey (3%), Roger Royse (1%), John Powers (1%), Jeff Krolick (1%) OUTLINE 1.

S patient, tumor, oncologist, drugs, tissue, assay, dose, functional testing, therapies, biopsy, test, treatments, cells, question, chris, developed, sensitivity, dose response curves, number, results SPEAKERS Chris Apfel (72%), Brad Power (9%), Glenn Sabin (5%), Arra Yerganian (4%), Amit Gattani (4%), Brian McCloskey (3%), Roger Royse (1%), John Powers (1%), Jeff Krolick (1%) OUTLINE 1.

Functional testing services for cancer patients. (0:00) 2.Cancer research and personalized medicine. (2:52) 3.Using in vitro assays to predict cancer treatment response. (9:14) 4.Personalized cancer treatment using tumor microenvironment. (15:54) 5.Personalized cancer treatment using AI-powered drug sensitivity analysis. (22:04) 6.Cancer testing and treatment options. (29:09) 7.

Personalized cancer treatment using tissue samples. (36:11) 8.Personalized cancer treatment dosing. (42:43) 9.Personalized cancer treatment strategies. (49:21) 10.Cancer diagnostic test development and commercialization. (55:42) 11.Cancer treatment and drug development. (1:01:18) SUMMARY ●Functional testing services for cancer patients.

0:00 ○Chris Apfel, a scientist and MD by background, co-founded a startup to provide functional testing services after experiencing the challenges of his parents' cancer treatment. ○He shares his personal story and discusses how functional testing can help patients make informed decisions about their treatments, with examples from his work at UCSF. ●Cancer research and personalized medicine.

2:52 ○Chris Apfel thanks others for introductions, shares personal experience with cancer research. ○His personal experience with cancer treatment inspires him to create a unique solution for personalized chemotherapy treatment. ○Cancer patients often lack effective treatments due to lack of driver mutations and tumor heterogeneity. ●Using in vitro assays to predict cancer treatment response.

9:14 ○Chris Apfel highlights the potential of in vitro testing for cancer treatment personalization, citing study with 90% negative predictive value. ○In vitro tumor growth is challenging due to limited proliferative materials, with low success rates (30% in some cases) and long growth times (3-6 weeks).

“Identifying the Most Effective Treatment on the Tumor Rather than Trying It Out on the Patient” (Dr. Chris Apfel) [#84] ○An oncologist's belief that a treatment doesn't work may be due to lack of data, not actually testing its effectiveness. ●Personalized cancer treatment using tumor microenvironment.

15:54 ○Chris Apfel highlights the need for clinical trials to prove the effectiveness of chemosensitivity testing, with over 75% of oncologists surveyed expressing interest in using the test despite potential lack of insurance coverage.

○He suggests developing a new assay to improve upon existing chemosensitivity testing methods, citing the need to better understand tumor resistance and improve patient outcomes.

estion, chris, developed, sensitivity, dose response curves, number, results SPEAKERS Chris Apfel (72%), Brad Power (9%), Glenn Sabin (5%), Arra Yerganian (4%), Amit Gattani (4%), Brian McCloskey (3%), Roger Royse (1%), John Powers (1%), Jeff Krolick (1%) OUTLINE 1.Functional testing services for cancer patients. (0:00) 2.Cancer research and personalized medicine. (2:52) 3.

Using in vitro assays to predict cancer treatment response. (9:14) 4.Personalized cancer treatment using tumor microenvironment. (15:54) 5.Personalized cancer treatment using AI-powered drug sensitivity analysis. (22:04) 6.Cancer testing and treatment options. (29:09) 7.Personalized cancer treatment using tissue samples. (36:11) 8.Personalized cancer treatment dosing. (42:43) 9.

Personalized cancer treatment strategies. (49:21) 10.Cancer diagnostic test development and commercialization. (55:42) 11.Cancer treatment and drug development. (1:01:18) SUMMARY ●Functional testing services for cancer patients.

0:00 ○Chris Apfel, a scientist and MD by background, co-founded a startup to provide functional testing services after experiencing the challenges of his parents' cancer treatment. ○He shares his personal story and discusses how functional testing can help patients make informed decisions about their treatments, with examples from his work at UCSF. ●Cancer research and personalized medicine.

2:52 ○Chris Apfel thanks others for introductions, shares personal experience with cancer research. ○His personal experience with cancer treatment inspires him to create a unique solution for personalized chemotherapy treatment. ○Cancer patients often lack effective treatments due to lack of driver mutations and tumor heterogeneity. ●Using in vitro assays to predict cancer treatment response.

9:14 ○Chris Apfel highlights the potential of in vitro testing for cancer treatment personalization, citing study with 90% negative predictive value. ○In vitro tumor growth is challenging due to limited proliferative materials, with low success rates (30% in some cases) and long growth times (3-6 weeks).

“Identifying the Most Effective Treatment on the Tumor Rather than Trying It Out on the Patient” (Dr. Chris Apfel) [#84] ○An oncologist's belief that a treatment doesn't work may be due to lack of data, not actually testing its effectiveness. ●Personalized cancer treatment using tumor microenvironment.

15:54 ○Chris Apfel highlights the need for clinical trials to prove the effectiveness of chemosensitivity testing, with over 75% of oncologists surveyed expressing interest in using the test despite potential lack of insurance coverage.

○He suggests developing a new assay to improve upon existing chemosensitivity testing methods, citing the need to better understand tumor resistance and improve patient outcomes.

ing chemosensitivity testing methods, citing the need to better understand tumor resistance and improve patient outcomes. ○He explains that their method uses fresh cancer biopsies to create live 3D microtumors within a day, mimicking the patient's body and retaining the microenvironment and heterogeneity of the biopsy.

○The method aims to double the tumor response, significantly improve progression-free survival, and improve quality of life, while reducing costs. ●Personalized cancer treatment using AI-powered drug sensitivity analysis. 22:04 ○Researchers use confocal microscopy to analyze drug effectiveness in multiple myeloma cells, predicting high accuracy in tumor resistance prediction. ○Dr.

Konieczny's team tested various drugs for a patient with lung metastasis, finding that doxorubicin and cyclophosphamide were most effective. ○Developer of Sage direct tests for non-resectable solid tumors, including ovarian, glioblastoma, and pancreatic cancer. ●Cancer testing and treatment options.

29:09 ○Brad Power asks Chris about the input source needed for functional testing and the types of treatments tested, mentioning chemo and targeted therapies.

○Chris Apfel explains that functional testing requires fresh tissue, as fixed or formalin-preserved tissue is not viable, and their technology can work with minimal tissue samples, including tumor samples from pleural effusions or corneal biopsies. ○He explains that tissue samples can be obtained from bone for cancer diagnosis and treatment.

○Roger Royse questions the effectiveness of using tumor tissue for cancer treatment, citing preciousness of pancreatic tissue and limited predictive value of liquid biopsies. ●Personalized cancer treatment using tissue samples.

36:11 ○Researchers need 100 milligrams of tissue to test six main drugs on pancreatic cancer cells, but often have difficulty obtaining enough tissue due to limited access to tumor tissue. ○Patient with prostate cancer discusses the potential for keeping biological tissue alive in the lab for drug resistance testing.

○Researchers have not yet tested whether exposing tissue to drug X in a lab setting can accurately predict its effectiveness in a patient's body. ●Personalized cancer treatment dosing. 42:43 ○Patients can have vastly different plasma concentrations of the same drug dose due to individual factors such as body fat, metabolism, and gender.

○Chris Apfel emphasizes the importance of personalized dosing for cancer treatment, citing their own family experience. ○A researcher advocates for low-dose combination therapy to reduce side effects and improve cancer treatment outcomes. ●Personalized cancer treatment strategies.

49:21 ○Nik Schork, a key figure in the Aveiro trial, can provide valuable insights on precision medicine for bone cancer.

“Identifying the Most Effective Treatment on the Tumor Rather than Trying It Out on the Patient” (Dr. Chris Apfel) [#84] ○Early-stage tumors are more likely to be eradica