On May 2, 2024 Delphia Therapeutics, Inc. (Delphia), reported its launch today to pioneer a new area of cancer biology – activation lethality – which targets cancer’s surprising vulnerability to oncogene overactivation (Press release, Delphia Therapeutics, MAY 2, 2024, View Source [SID1234642617]). Leveraging this next-generation approach, Delphia is advancing highly differentiated first-in-class targeted cancer medicines with the potential for significant anti-tumor activity and more durable patient benefit across multiple prevalent cancer types. Delphia completed a $67 million Series A financing led by premier early life sciences investors including GV (Google Ventures), Nextech Invest, Polaris Innovation Fund and Alexandria Venture Investments.

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"Despite dramatic advances in the understanding and drugging of key driver mutations and oncogenic pathways, cancer remains a tremendous global health challenge, as tumors rapidly develop resistance to targeted therapy in the vast majority of patients," said Kevin Marks, Ph.D., co-founder, president and CEO of Delphia. "Our activation lethality platform offers the potential for new cancer medicines that are effective on their own while also combating the emergence of resistance to classic targeted therapies. These medicines hold the potential to address significant cancer patient populations and may mark a disruptive paradigm shift in how cancer is treated, leading to more sustained disease control and longer patient survival. We are thrilled to launch Delphia to lead this exciting new area of cancer biology."

Activation Lethality: Unlocking the Next Wave in Oncology Therapeutics

The problem of cancer drug resistance

Mutations in oncogenes drive cancer by boosting activity of key pathways that drive cell/tumor growth. Targeted therapies that inhibit oncogenes block pathway activity and typically lead to an initial response.
However, tumors are heterogeneous. Under the selective pressure of inhibitor therapy, drug resistance rapidly emerges – often pushing pathway activity even higher, leading to increased tumor growth and further disease progression.
Activation lethality

Breakthrough research led by Delphia’s founders has revealed that many oncogenic pathways are also highly vulnerable to overactivation1. Oncogene overactivation leads to an overload on cell stress pathways and is selectively lethal to cancers with mutations that put them close to the upper bounds of tolerable pathway activity (‘activation lethality’).
Activation lethal medicines

Critical cellular pathways have multiple layers of regulation to ensure optimal activity. Oncogenic mutations boost pathway activity and disable much of this regulation. In cells with oncogenic mutations, the remaining regulators are vulnerable – a ‘last line of defense’ from overactivation.
These key, vulnerable regulatory nodes represent unique therapeutic targets to drive overactivation and selective killing of tumor cells.
Delphia’s next-generation platform

Delphia integrates tumor genetics, novel functional genomic approaches, and studies of inhibitor drug resistance to identify targets that drive activation lethality.
Through its activation lethality platform, Delphia is advancing a pipeline of first-in-class cancer medicines that aim to better control oncogenic pathways.
"Delphia is advancing multiple strategies to hyperactivate oncogene pathways; I am enthusiastic about the potential of this new class of medicines, which also may open up avenues to alternate between pathway activation and inhibition as a way to durably keep tumor growth in check," said Bill Sellers, M.D., director of the cancer program of the Broad Institute of MIT and Harvard and co-founder and board member of Delphia. "I am excited to work alongside the Delphia team to leverage the company’s activation lethality platform to advance potential paradigm-shifting cancer medicines."

Delphia Co-Founders

Delphia was founded by industry leading oncology drug developers who have collectively been involved in the discovery, development and commercialization of more than 15 approved drugs.

Bill Sellers, M.D., director of the cancer program of 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
"Delphia’s activation lethality platform is one of the most innovative approaches in cancer drug development and offers an excellent foundation to build a differentiated oncology company," said David Schenkein, M.D., general partner and co-lead of the life sciences team at GV and Delphia board observer. "This opens up a new category of cancer genetics and therapeutic targets that have the potential to lead to better medicines for patients. We are thrilled to continue supporting Dr. Kevin Marks and the Delphia team after the company was incubated at GV through our entrepreneur-in-residence program, and we are excited to see this team of experienced cancer drug developers make major impacts on the lives of cancer patients."