Pharma Focus Europe

Delphia Therapeutics Introduces a Novel Field in Cancer Medicine: Activation Lethality

Friday, May 03, 2024

Delphia Therapeutics, Inc. unveiled its groundbreaking mission today: to pioneer a fresh frontier in cancer biology called activation lethality, aiming to exploit cancer's unexpected susceptibility to oncogene overactivation. Armed with this cutting-edge approach, Delphia is forging ahead to develop pioneering targeted cancer treatments that promise substantial anti-tumor efficacy and potentially longer-lasting benefits for patients battling various prevalent cancer types. The company has successfully closed a $67 million Series A financing round, spearheaded by esteemed early life sciences investors such as GV (Google Ventures), Nextech Invest, Polaris Innovation Fund, and Alexandria Venture Investments.

Delphia, remarked, “Despite significant strides in understanding and targeting key driver mutations and oncogenic pathways, cancer remains an immense global health challenge, with tumors swiftly evolving resistance to targeted therapies in the majority of cases. Our activation lethality platform presents a new frontier for cancer therapeutics, offering the promise of novel medicines that not only stand alone in their effectiveness but also combat the emergence of resistance to conventional targeted therapies. These medicines have the potential to address substantial populations of cancer patients and could herald a disruptive paradigm shift in cancer treatment, leading to more enduring disease management and enhanced patient survival. We are excited to launch Delphia to spearhead this thrilling new domain in cancer biology.”

Activation Lethality: Pioneering the Next Era in Oncology Treatments

The Challenge of Cancer Drug Resistance

  • Mutations in oncogenes propel cancer by amplifying the activity of crucial pathways driving cell and tumor growth. Targeted therapies that inhibit oncogenes curtail pathway activity, typically triggering an initial response.
  • However, tumors exhibit heterogeneity. Under the selective pressure of inhibitor therapy, drug resistance swiftly arises—often elevating pathway activity further, fostering increased tumor growth, and exacerbating disease progression.

Activation Lethality

  • Pioneering research led by Delphia's founders has unveiled that many oncogenic pathways harbor significant vulnerability to overactivation. Oncogene overactivation triggers an overload on cellular stress pathways, selectively inducing lethality in cancers with mutations driving them perilously close to the upper thresholds of tolerable pathway activity ('activation lethality').

Activation Lethal Medicines

  • Critical cellular pathways boast multiple layers of regulation to maintain optimal activity. Oncogenic mutations enhance pathway activity and incapacitate much of this regulation. In cells bearing oncogenic mutations, the remaining regulators become vulnerable—a 'last line of defense' against overactivation.
  • These pivotal, vulnerable regulatory nodes represent distinctive therapeutic targets to drive overactivation and selectively eliminate tumor cells.

Delphia's Next-Generation Platform

  • Delphia integrates tumor genetics, innovative functional genomic methodologies, and investigations of inhibitor drug resistance to pinpoint targets driving activation lethality.
  • Through its activation lethality platform, Delphia is advancing a pipeline of first-in-class cancer treatments designed to more effectively regulate oncogenic pathways.

Delphia, expressed his enthusiasm, stating, “Delphia is pursuing multiple strategies to hyperactivate oncogene pathways; I am optimistic about the potential of this new class of medicines, which could also open avenues to alternation between pathway activation and inhibition as a means of durably controlling tumor growth. I am eager to collaborate with the Delphia team to harness the company's activation lethality platform to advance potential paradigm-shifting cancer treatments.”

Delphia Co-Founders

Delphia was established by a team of leading oncology drug developers with a collective track record encompassing the discovery, development, and commercialization of over 15 approved drugs.

  • Bill Sellers, M.D., director of the cancer program at the Broad Institute of MIT and Harvard
  • Mike Dillon, Ph.D., former chief scientific officer of IDEAYA Biosciences and former global head of discovery chemistry for oncology at Novartis Institutes for BioMedical Research (NIBR)
  • Kevin Marks, Ph.D., president and CEO of Delphia, entrepreneur-in-residence at GV, and former oncology drug discovery site head at NIBR

David Schenkein, M.D., general partner and co-lead of the life sciences team at GV and Delphia board observer, praised Delphia's innovative approach, stating, “Delphia’s activation lethality platform represents one of the most innovative approaches in cancer drug development and provides a solid foundation to establish a distinct oncology company. This introduces a new category of cancer genetics and therapeutic targets with the potential to yield superior medicines for patients. We are delighted to continue supporting Dr. Kevin Marks and the Delphia team following the company’s incubation at GV through our entrepreneur-in-residence program, and we look forward to witnessing the impactful contributions of this experienced team of cancer drug developers to the lives of cancer patients.”



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