Ep175: Andy Scharenberg on in vivo CAR-T cell therapies

Episode Summary

Executive Summary: Andy Scherenberg traced Umoja Biopharma’s origin from decades of immunology, gene therapy, and CAR-T experience to a new goal: deliver CAR-T functionality in vivo with a single shot. He explained how Umoja combines lentiviral delivery, a survival/anti-inflammatory RACER receptor, and tumor-tag targeting to make CAR-T more scalable, safer, and potentially usable for community oncology and solid tumors.

Main Topics: From pediatric immunology to biotech entrepreneurship (Priority: 5/5): Scherenberg described his path from West Lafayette, Indiana, to medicine, immunology, and a physician-scientist career at Seattle Children’s, where he worked on inherited immune disorders and gene therapy. Why ex vivo CAR-T is limited (Priority: 5/5): He emphasized that while CAR-T can be transformative, current autologous manufacturing is slow, expensive, and inaccessible to most patients, especially those who cannot wait months for treatment. The scientific basis of Umoja’s in vivo CAR-T platform (Priority: 5/5): Umoja’s core thesis is to deliver a CAR gene directly into the body using lentiviral vectors, aiming to reprogram T cells in situ rather than engineering them outside the body. RACER and tumor-tag technologies (Priority: 4/5): Scherenberg explained additional platform components: RACER to promote CAR-T persistence and suppress unwanted immune responses, and tumor-tag to broaden targeting and address antigen heterogeneity in solid tumors. Clinical translation and early trials (Priority: 5/5): He described Umoja’s first clinical programs in CD19 and CD22 malignancies, the IND clearance for the CD19 program, and expectations for initial readouts by late 2025. Manufacturing, scale, and competitive advantage (Priority: 4/5): The company chose to build internal manufacturing capacity during COVID, arguing that a new modality requires iterative scientist-engineer collaboration and proprietary know-how not easily outsourced. Long-term vision for accessible curative therapy (Priority: 4/5): Scherenberg said the aim is a community-oncologist-deliverable, single-shot therapy that could extend CAR-T benefits to far more patients and eventually support repeat dosing or multi-antigen approaches.

Key Arguments: CAR-T works remarkably well, but today’s autologous model excludes most eligible patients because it is slow, costly, and operationally complex. Lentiviral vectors are uniquely powerful delivery vehicles because they can efficiently and stealthily deliver genetic payloads to cells in vivo. Gene editing alone is not enough; delivery remains the central bottleneck in both ex vivo and in vivo approaches. Umoja’s platform is designed as an integrated system: delivery (VivoVec), persistence/safety modulation (RACER), and broader tumor targeting (tumor-tag). Avoiding lymphodepletion could reduce toxicity and make repeat treatment or sequencing of therapies more feasible than with current CAR-T methods. Solid tumors likely require flexible, multi-antigen targeting because single-antigen escape is a common mechanism of relapse. Internal manufacturing was necessary because developing a new modality requires rapid iteration and proprietary process knowledge, which CDMOs are less suited to provide early on. The company believes its non-human primate data and early clinical progress place it ahead of competitors in in vivo CAR-T.

Data Points: Umoja founding year: 2019 - Company founded by Scherenberg, Mike Jensen, and Phil Lau to solve CAR-T access problems. Umoja Series C financing: $100 million - Raised at the start of 2025 to advance clinical development. Estimated access gap for CAR-T: 10%–15% - Scherenberg estimated only a small fraction of patients who could benefit from CAR-T have been able to access it. Seattle Children’s time allocation: 20%–25% clinic, 75% research - Early faculty career split between patient care and laboratory work, later shifting toward 10% clinic and 90% lab. Initial company investment from his father: $100,000 - Seed capital for the first IP-holding corporation behind the megatal technology. Progenin exit value: ~$170 million total potential; ~50 million upfront/initial milestones - Scherenberg cited a strong outcome from the company that originated the earlier gene-editing IP. CAR-T referral-to-treatment time: >100 days - Average time from diagnosis/referral to CAR-T administration for commercial products. Relapse rate after CAR-T: ~60% - Scherenberg noted many CAR-T patients relapse, often with CD19-negative disease. Umoja clinical programs: 2 - Initial in vivo CAR-T programs in CD19 and CD22 malignancies. IND status: Cleared in July 2025 - First and only IND for an in vivo CAR-T therapeutic in the United States, for the CD19 program. Initial trial timing: Enrolling in early 2025; initial data expected by late 2025 - Both CD19 and CD22 trials were described as actively enrolling with first readouts anticipated by year-end. Non-human primate CAR-T activity: >50% of circulating T cells - After delivery, more than half of circulating peripheral blood T cells became CAR-T cells in primate studies. B-cell depletion in primates: Complete loss of detectable B cells - Used as a pharmacodynamic marker for B-cell-targeting activity. CAR-T persistence in primates: Up to 75 days - Observed in animals not generating limiting antibodies against the CAR component. Prize competition amount mentioned in sponsor spot: >$500,000 - TBXT challenge prize pool announced in the sponsorship message.

Pivotal Quotes: "Any patient, any time, any tumor" — Andy Scherenberg: Original thesis for Umoja’s platform: make CAR-T broadly accessible and deployable anywhere. "We know we can do it, we don't know exactly how we're going to do it" — Andy Scherenberg: Early company formation mindset: conviction in the concept before all engineering details were solved. "The great part is that you only need to come up with the compounds. The competition organizers handle biophysical evaluation of submitted compounds." — Luke Timmerman / sponsor message: Announcement of the TBXT drug discovery prize competition.

Implications: If Umoja’s early human data are positive, in vivo CAR-T could lower cost, shorten time to treatment, and broaden access beyond major centers. Success would also reshape solid-tumor targeting and reduce dependence on ex vivo manufacturing.