Welcome to Partnology’s Biotech Leader Spotlight Series, where we highlight the remarkable accomplishments and visionary leadership of biotech industry pioneers. This series is about showcasing the groundbreaking strides made by exceptional leaders who have transformed scientific possibilities into tangible realities. Through insightful interviews, we invite you to join us in following the inspiring journeys of these executives who continue to shape the landscape of the biotech industry. This week we are recognizing:
John Langowski, PhD, is a seasoned drug discovery and cell therapy leader with more than two decades of experience advancing cell therapies, small molecules, and biologics from early discovery through IND-enabling studies and into the clinic. He currently serves as Chief Scientific Officer at Micoy Therapeutics, advising a novel autoimmune-focused startup on scientific strategy and preclinical proof-of-concept work. Prior to that, John spent seven years at Kite Pharma, where he progressed through multiple leadership roles—ultimately serving as Vice President of Cell Therapy Research and Site Head for both the Emeryville and Foster City research sites. Earlier in his career, John held roles of increasing responsibility at Nektar Therapeutics, where he led preclinical biology efforts for cytokine-based immunotherapies, and at Novartis, where he served as pharmacology lead for multiple oncology programs and contributed to IND submissions and translational strategy.
John began his scientific career as a Postdoctoral Fellow at the DNAX Research Institute (currently Merck Research Laboratories), conducting foundational work on IL-23 biology that led to a highly cited publication and advanced understanding of cytokine-driven tumorigenesis. He holds a PhD in Immunology from the UT MD Anderson Cancer Center UTHealth Houston Graduate School of Biomedical Sciences and a BS in Molecular Biology from The University of Texas at Austin.
Tell me more about Micoy Therapeutics and what you’re currently working on:
Micoy is primarily focused on understanding how the development of autoantibodies against cytokines and growth factors—which can block their normal function—impacts the incidence and progression of multiple diseases. One example is type I interferons, a family of cytokines that play a critical role in antiviral immunity. Recent studies have shown that nearly 1 in 15 people aged 65 and older carry autoantibodies against type I interferons, which directly impairs their ability to mount an effective immune response. During the COVID-19 pandemic, for instance, researchers found that almost 20% of patients with life-threatening or fatal disease carried these autoantibodies.
There is also a significant interplay between viral infection and cancer, making it important to understand the role of these autoantibodies in oncology. We already know that interferon alpha has direct anti-tumor activity and is a potent stimulator of antigen-presenting cells. The loss of type I interferon signaling due to autoantibodies could therefore negatively impact the effectiveness of immune-mediated therapies. To address this, Micoy has developed a selective decoy designed to neutralize these autoantibodies while avoiding activation of the cognate receptor. The goal is to develop this decoy as a therapeutic capable of restoring normal immune function. That said, type I interferon biology is complex, and its role in anti-tumor immunity is likely contextual and dependent on cancer type or stage. So there is a significant foundation of translational work that we still need to accomplish.
Having led one of Kite’s research groups, a pioneer in CAR-T therapies, how do you see the next generation of cell therapies evolving — in terms of durability, safety, and accessibility?
It has been incredibly exciting to watch this therapy evolve. I think I can speak for most researchers when I say that we all dream of making a meaningful impact on patients’ lives, so seeing the efficacy of CAR-T in B-cell malignancies has been especially rewarding. That said, the role of research is always to push outcomes further. Following the success of single-antigen CAR-T therapies, the field is now advancing toward multi-antigen targeting to address relapse and improve response rates. There has also been substantial work focused on potentiating CAR-T activity—for example, engineering cytokine secretion (“armoring”) to enhance both CAR-T function and the broader immune response.
Despite the remarkable clinical impact, accessibility remains a major challenge, driven in part by the cost and complexity of manufacturing. The industry continues to make advances through more efficient closed systems, automation, and streamlined processes. Reducing manufacturing time is another key improvement: faster turnaround not only lowers cost but can increase potency, since CAR-T cells that undergo fewer rounds of expansion often require lower doses and may carry a lower risk of side effects.
We have learned a great deal about managing safety concerns—particularly cytokine release syndrome, which can often be addressed with medical management and IL-6 blockade. Neurotoxicity remains more difficult to mitigate, as its causes are likely multifactorial, involving conditioning chemotherapy, tumor burden, CAR-T expansion kinetics and other factors. Both toxicities must be carefully evaluated as next-generation engineering seeks to deepen response rates.
One approach with significant potential to improve both cost and accessibility is in vivo CAR-T. Instead of generating CAR-T cells ex vivo and reinfusing them, this strategy aims to engineer CAR-T cells directly inside the patient using targeted lipid nanoparticles delivering mRNA or viral vectors. Several clinical trials are underway, with encouraging early results. However, we still need longer-term data on durability of response and safety to understand how it compares to the traditional ex vivo method. Even so, the approach is highly promising.
You’ve led drug discovery efforts across small molecules, biologics, and cell therapies — how do you think about scientific strategy differently across these modalities?
First, if you boil it down, there are many commonalities across modalities. Everything starts with the target—especially in solid tumors, where truly target-specific antigens are hard to find. You have to ask: What are the consequences of hitting this target in normal tissue? Is there a viable therapeutic window? Closely related off-targets or family members can be problematic due to their expression in healthy tissues, and traditional drug development often spends significant time evaluating whether those off-target effects can be avoided. If they can’t, it may require rethinking target selection altogether.
In cases where these risks can be mitigated—or where the target still offers strong clinical potential despite them—having robust, translatable biomarkers for both efficacy and toxicity becomes crucial. It’s also important to determine whether any associated toxicities can be monitored and reversed if therapy is discontinued, which is a core consideration in classical drug development.
Beyond these shared principles, each modality carries its own unique challenges. Small-molecule kinase inhibitors can deliver strong single-agent efficacy, but tumors often activate parallel pathways, leading to rapid acquired resistance—prompting consideration of rational combination strategies. Tumor heterogeneity also limits the impact of single agents, though modalities like antibody-drug conjugates can partially overcome this through “bystander effects,” where released payload diffuses into neighboring antigen-negative cells.
For CAR-T therapies, the impact in solid tumors is still developing. While CAR-T cells are typically restricted to a single target, additional engineering—such as armoring or cytokine modulation—may help stimulate a broader immune response within the tumor microenvironment. These engineering strategies may also be necessary to counter the many mechanisms tumors have evolved to evade immune surveillance.
When evaluating a new therapeutic concept or target, what early signals or criteria do you look for to determine whether it’s worth advancing toward IND?
I think one of the most challenging aspects is that in any strong research organization, there is rarely a shortage of great scientific ideas. The difficult part is determining which ones are truly the most promising to advance. There’s a substantial amount to evaluate scientifically, but successful development also requires a deep understanding of the indication from a business perspective—a challenge for many scientists who have limited exposure to that thinking early in their careers. Moving a concept from discovery to IND is time-consuming and costly; Phase 1 trials are even more so, and Phase 3 introduces another significant hurdle when comparing against standard of care. It can feel uncomfortable to acknowledge the financial realities of drug development, but any concept we choose to advance must make business sense for a company or investor to support it.
That means we must look not only for targets and indications with meaningful unmet need, but also carefully assess the competitive landscape. What are the gaps in the current standard of care? What else is in development? Does the concept simply iterate on existing options, or does it represent a true evolution in therapy? Beyond the scientific rigor we apply in preclinical development, these are often the harder questions to answer. There is also a compelling strategy of starting with a smaller, well-defined patient population—such as an orphan indication—with the goal of expanding into larger related disease areas. This approach not only brings promising therapies to patients with rare diseases sooner, but can also accelerate overall development timelines.
Having worked on both immuno-oncology and autoimmune diseases, how do you see immune modulation strategies converging between these two fields?
I think there are two main areas to highlight—one centered on targets and the other on therapeutic approach. In B-cell malignancies, targeting CD19 alone or in combination with antigens like CD20 has demonstrated impressive efficacy. Similarly, targeting BCMA has shown strong clinical progress in multiple myeloma. In an autoimmune setting, targeting CD20 to eliminate B-cell populations responsible for producing autoantibodies can be highly effective, but optimal clinical responses are harder to achieve in patients with severe disease and results have been mixed in indications like lupus. Certain B-cell subsets not targeted by CD20 likely contribute to ongoing disease activity and the limitations in this approach.
Following the remarkable 2021 results of CD19-directed CAR-T cells in systemic lupus erythematosus (SLE), there has been a surge of activity in this space, with CAR-T approaches now being explored not only in SLE but also in lupus nephritis, multiple sclerosis, myasthenia gravis, and other autoimmune indications. While many early studies focused on CD19, newer efforts are evaluating additional antigens—including BCMA and CD20—both as single targets and in combination with CD19.
However, traditional ex vivo CAR-T therapy requires lymphodepletion prior to administration, which is essential for engraftment and efficacy in oncology. In patients with autoimmune disease, this step can be particularly problematic due to its substantial side-effect profile. One potential solution is the use of in vivo CAR-T therapy, which does not require lymphodepletion and is now gaining significant traction in autoimmune indications. Several clinical programs are underway, with encouraging early data.
There has also been considerable progress in T-cell engagers for autoimmune disease, leveraging oncology experience with CD19, CD20, and BCMA coupled to CD3-engaging domains. While less complex than cell therapy, these therapies are not without challenges—namely toxicity, and a narrow therapeutic window. The induction of T-cell exhaustion with this approach may be beneficial in suppressing autoreactive T cells, but the increased infection risk may require careful study.
Finally, another promising strategy focuses on restoring natural self-tolerance by targeting regulatory T cells (Tregs). There is already compelling data from direct Treg stimulation approaches, such as the modified IL-2 molecule rezpegaldesleukin, for which I contributed to preclinical development at Nektar Therapeutics. In parallel, many insights from the CAR-T field are now being applied to engineering Tregs for conditions including type 1 diabetes, inflammatory bowel disease, and even liver transplantation. Some of these approaches use polyclonal Tregs, while others are antigen-specific. It’s an incredibly exciting time for the field.
What trends in biotech R&D excite you most right now — and which ones do you think are overhyped?
The advent of genetic medicine is here, and I’m genuinely excited to see where it takes us. We’re now combining major advances in in vivo targeting with decades of work uncovering how specific genes drive cellular function and human disease. We’re only beginning to see the impact across oncology, inflammation, metabolic diseases, and even aging. There is still much to learn clinically, but it feels as though we’re only scratching the surface of what’s possible.
I’d also be remiss not to mention AI—now a catch-all term encompassing a wide range of technologies. How can AI transform diagnosis, clinical trial design, or biomarker discovery? Can we map complex cellular networks within tumors to better understand the microenvironment or identify new targets? With the right training datasets, AI could meaningfully support de novo drug design and lead optimization. We already have examples like AlphaFold for protein structure prediction, and the first AI-guided drugs have now entered clinical trials. Many more will inevitably follow.
I try to avoid labeling anything as overhyped. Early in my career, oncology conferences were dominated by small-molecule posters—until checkpoint inhibitors arrived and rightfully drew huge crowds. It’s natural to be energized by new therapeutic approaches, but the real work continues steadily behind the scenes. Consider small molecules: we are now seeing KRAS inhibitors—a target once considered undruggable—enter development, along with increasingly selective or mutation-specific inhibitors for established targets. Antibody–drug conjugates continue to advance with new targets and next-generation payloads. T-cell engagers are evolving into tri-specific formats and exploring alternative activation strategies, such as NK-cell engagement. Each success reinvigorates interest in that modality, and the field continues to move in cycles.
Ultimately, by combining hard-earned clinical lessons with the rapidly accelerating pace of scientific innovation, I believe we’ll keep delivering better and more impactful therapies for patients.
