Stopping Shape-Shifting Tumors with a First-in-Class Epigenetic Drug
K36 Therapeutics is pioneering a first-in-class epigenetic drug targeting NSD2, a key driver in aggressive, treatment-resistant cancers like neuroendocrine prostate cancer and multiple myeloma. The company’s lead compound, K36-1001, is in clinical trials for myeloma and prostate cancer, with a strategic focus on preventing cancer cells from 'shape-shifting' into more dangerous forms through lineage plasticity. What makes this approach revolutionary is not just the target—NSD2—but the fact that it becomes a cancer dependency through multiple distinct mechanisms: genetic translocations, gain-of-function mutations, and adaptive upregulation. This convergence of biology across hematologic and solid tumors suggests broad therapeutic potential. Despite the challenges of raising capital in a tough biotech environment, K36 has secured $100 million by demonstrating real clinical assets early. CEO Terry Connolly emphasizes that being first-in-class is both an advantage and a hurdle—investors are excited by the science but cautious about unproven pathways. Yet, growing interest from both existing and new investors signals a shift in sentiment, especially as epigenetic therapies gain momentum with phase 3 trials from companies like Pfizer and Oric. The company’s path forward includes advancing combination therapies, refining biomarker-driven patient selection, and building toward a registrational strategy in high-need populations.
NSD2 is a master regulator of cancer lineage plasticity, enabling tumors to shift into aggressive, treatment-resistant forms like neuroendocrine prostate cancer.
K36-1001 targets NSD2 through multiple mechanisms—genetic translocations, gain-of-function mutations, and adaptive overexpression—making it a broad-spectrum epigenetic therapy.
The company is advancing K36-1001 in three combination cohorts for multiple myeloma and completing dose escalation in prostate cancer with darolutamide.
Being first-in-class is a double-edged sword: it attracts scientific excitement but demands stronger clinical validation to reassure conservative investors.
K36 has raised $100 million by demonstrating clinical assets early, with current capital funding key inflection points over the next 18 months.
…and 3 more takeaways available in PodZeus
Sponsor: Prevail Infoworks
Sponsorship announcement for Prevail Infoworks, highlighting their role in enabling real-time clinical trial monitoring and data analysis, which accelerates development timelines and improves capital efficiency.
NSD2 and Treatment-Emergent Neuroendocrine Prostate Cancer
“Our strategy is to move quickly into combinations with darolutamide where we think we can potentially prevent or resist that shift and restore sensitivity or have patients remain responsive to AR pathway inhibitors.”
The Three Mechanisms of NSD2 Dysregulation
“The net effect is that you make more of this K36 dimethyl with the same amount of enzyme, and essentially you net out at the same biology as you would if you overexpress the protein.”
Broad Therapeutic Potential Across Cancers
“I believe that this is a pathway that cancer finds, it turns on, and it very quickly realizes that with upregulation of this pathway, there's a benefit for it.”
Capital Strategy and Clinical Progress
K36 has raised $100 million by demonstrating clinical assets early. Current capital funds key milestones: advancing 1001 in myeloma combinations and completing dose escalation of 2001 in prostate cancer.
“So the net effect is that you make more of this K36 dimethyl with the same amount of enzyme, and essentially you net out at the same biology as you would if you overexpress the protein.”
“So our strategy is to move quickly into combinations with derolutamide where we think we can potentially prevent or resist that shift and restore sensitivity or have patients remain. responsive to AR pathway inhibitors.”
“So I believe that this is a pathway that cancer finds, it turns on, and it very quickly realizes that with... upregulation of this pathway, there's a benefit for it.”
Host
Guest
NSD2
other
prostate cancer
other
Terry Connolly
person
multiple myeloma
other
K36 Therapeutics
organization
Prevail Infoworks
organization
mantle cell lymphoma
other
Pfizer
organization
EZH2
other
Oric
organization
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