October 12, 2022
October 11, 2022 | Jessica Kim Cohen – genomeweb
NEW YORK – Genetika+ is combining information on patients’ symptoms, pharmacogenetics, and aso-called “brain-in-a-dish” functional testing model in the hopes of improving personalized drugprescribing for psychiatric conditions, with an initial focus on depression.
The Israeli company plans to launch its first drug-matching testing service for major depressivedisorder, dubbed NeuroKaire, next year. Genetika+ hopes to promote NeuroKaire as a service doctorscan use to improve patients’ outcomes on antidepressants, reduce treatment-related side effects, andcut down on trial-and-error prescribing.
Millions of people across the globe struggle with major depressive disorder, and prevalence hasincreased with the COVID-19 pandemic. About one-third of patients see success with the firstantidepressant they’re prescribed, and patients try out up to four antidepressants before theirsymptoms subside, according to one study.
It can take four to six weeks to determine whether an antidepressant is working as expected, saidGenetika+ Cofounder and CEO Talia Cohen Solal. If it isn’t, the patient must return to their doctor andtry a different drug. “That keeps going,” over and over, until the patient finds a suitable medication, saidCohen Solal, who has a PhD in neuroscience.
Genetika+ started prospective clinical trials to validate its antidepressant-matching platform earlier thisyear, and if all goes well, plans to begin offering commercial testing services by mid-2023, Cohen Solalsaid. The company, founded in 2018, received €17.5 million ($17.3 million) over the summer from theEuropean Commission’s European Innovation Council Accelerator to clinically validate and bringNeuroKaire to market. Before this, Genetika+ had raised $10 million in a Series A funding round.
The firm secured the CE mark for NeuroKaire in March. In the US, Genetika+ will offer NeuroKaire as atesting service through a CLIA-certified lab. The company plans to open its first US lab in New Jerseyby year end.
Physicians ordering Genetika+’s drug-matching services will collect blood samples from patients andsend them to its clinical lab for testing. Based on analysis of the blood sample and information frompatients, Genetika+ provides three reports to ordering physicians. The first test report details thepharmacogenetic markers impacting the patient’s ability to metabolize various antidepressants.
The second report describes the patient’s history of depression symptoms, based on an onlinequestionnaire filled out by the patient. These patient-reported symptoms are also an importantconsideration when personalizing treatment decisions. If a patient is struggling to get out of bed, forexample, a physician might want to avoid prescribing a drug that’s known to cause drowsiness, CohenSolal said.10/11/22, 10:00 AM Genetika+ Combines PGx, ‘Brain-in-a-Dish’ Model to Personalize Depression Meds | GenomeWeb https://www.genomeweb.com/molecular-diagnostics/genetika-combines-pgx-brain-dish-model-personalize-depression-meds#.Y0V9aezMJH1 2/3
For the third report, Genetika+ creates what it calls a “brain-in-a-dish.” The company turns cells from apatient’s blood sample into induced pluripotent stem (iPS) cells that it uses to create prefrontal corticalneurons — the kind of neurons affected in mental illness, Cohen Solal said. From there, Genetika+exposes the neurons to various antidepressants to see which drugs or drug combinations have the”strongest impact on rescuing the connections,” she said.
That provides a level of information beyond pharmacogenetic testing, according to the company, sinceit speaks to how the brain itself may respond to a given antidepressant.
All in all, it takes Genetika+ four to six weeks to return results to a physician. Daphna Laifenfeld, thecompany’s cofounder and chief strategy officer, who also has a PhD in neuroscience, acknowledgedthat the turnaround time for the firm’s testing service is longer compared to that claimed by labs sellingsimpler pharmacogenetic tests, which can range from a few days to up to two weeks. Still, Laifenfeldmaintained that Genetika+ is returning results in a time frame that will still be useful to patients.
Genetika+ sends its therapy recommendations — based on findings from the three reports — to thepatient’s physician as a PDF, which categorizes medications as green, orange, or red to delineatewhether a particular drug is expected to be a good fit or should be avoided. If a medication is listed inthe orange category, that means the drug might be contraindicated.
Researchers at Genetika+, including Laifenfeld and Cohen Solal, published a study in TranslationalPsychiatry last year describing the biomarkers they’ve identified in iPS cells that are associated withpatients’ responses to antidepressants, including synaptic connectivity, morphology changes, andvarying gene expression.
So far, Genetika+ has validated its platform for 35 drugs covering the five major classes ofantidepressants, and the company plans to add more, Cohen Solal said. The team is actively workingto add an indication for matching schizophrenia patients to the right drugs and eventually wants toexpand into attention deficit hyperactivity disorder and bipolar disorder.
“We consider ourselves the ‘precision medicine for the brain’ platform,” Cohen Solal said.
Precision prescribing for antidepressants is an active area for pharmacogenomics testing firms, eventhough not all physicians are convinced of their utility and some want more evidence that testingimproves patients’ outcomes.
Treatment for major depressive disorder varies by patient, but might involve antidepressants andpsychotherapy, said Chang-Gyu Hahn, a psychiatrist and a principal investigator on the research teamat Philadelphia-based Thomas Jefferson University that’s participating in a trial with Genetika+. Theteam is enrolling patients with major depressive disorder who have a known history of responsivenessor resistance to certain antidepressants.
If a patient doesn’t respond to the first antidepressant they try, such as a selective serotonin reuptakeinhibitor, the evidence available today isn’t very instructive on what to do next, Hahn said. He’sinterested in whether Genetika+’s approach will provide information that helps to navigate suchcomplexity and understand why people respond to different antidepressants.
Hahn is curious to what extent Genetika+’s model will strengthen the predictive power to identify theright depression treatments for patients beyond typical pharmacogenetic testing. “It will be wonderfulto see how this integrative approach could serve to predict one’s clinical responsiveness toantidepressants and ultimately help patients who suffer from depression,” he said.10/11/22, 10:00 AM Genetika+ Combines PGx, ‘Brain-in-a-Dish’ Model to Personalize Depression Meds | GenomeWeb https://www.genomeweb.com/molecular-diagnostics/genetika-combines-pgx-brain-dish-model-personalize-depression-meds#.Y0V9aezMJH1 3/3
While Genetika+’s approach is more extensive than pharmacogenomic testing alone — and thus maytake more time and have higher costs — that’s not necessarily a downside if the test succeeds inimproving patient care, he said.
If Genetika+ is successful in commercializing NeuroKaire, it plans to market the test to physiciansprescribing antidepressants, such as psychiatrists and general practitioners. The company’scofounders expect doctors could submit for insurance coverage using existing CPT codes forpharmacogenetics testing, since their product incorporates pharmacogenetics. There could be a copayof up to $300, according to Cohen Solal.
Genetika+ is also striking partnerships with pharmaceutical firms, a business that Cohen Solal expectsto contribute up to half of the company’s revenue. She likened the business model to FoundationMedicine, a developer of cancer tumor profiling assays that also partners with drugmakers to identifybest responders to their treatments and stratify patients in drug trials. Foundation Medicine, founded in2010 and since acquired by Roche, has partnered with more than 65 biopharma partners, according toits website.
Pharmaceutical companies can use Genetika+’s platform and biobank of de-identified patient data tostudy new antidepressants. Cohen Solal said there’s also an opportunity for pharma companies withfailed investigational antidepressants to revive those programs in more specific patient subsets, forexample. Genetika+ also supports pharmaceutical companies to identify clinical trial candidates, stratifypatients, and advance companion diagnostics.
That could prove helpful as the company expands beyond major depressive disorder and into diseaseslike Alzheimer’s and Parkinson’s — conditions where patients don’t have many treatment options tochoose from.
“We want the patient to get the right drug for them, but it would be even better if there were even betterdrugs on the market, as well,” Cohen Solal said.
About Genetika+
Genetika+, founded in 2018 by Talia Cohen-Solal, Ph.D., and Daphna Laifenfeld, Ph.D., is developing personalized medicine solutions to optimize treatment for psychiatric and neurological diseases. The company’s Brain-in-a-Dish technology helps physicians find the best treatment for their patients. In its first indication, depression, Genetika+ uses patented technology to rapidly test more than 70 approved antidepressants and drug combinations against an individual patient’s unique neurological biomarkers. Combined with patients’ genetic and medical history, Genetika+ can predict the optimal drug or combination therapy for each patient. This opens the door to faster treatment, fewer side effects, and lower dosing, and the elimination of arduous trial-and-error treatment protocols and needless loss of life. To learn more, follow us on LinkedIn or on Twitter @Genetikaplus.