Multi-node PI3K inhibition reaches clinical testing

Overview

Updated May 29

Lewis Cantley discovered the PI3K enzyme in 1985. Four decades later, a combination therapy targeting multiple nodes of the pathway he uncovered just demonstrated an 80% response rate in endometrial cancer patients—triple the historical rate with chemotherapy alone. Sensei Biotherapeutics acquired Faeth Therapeutics and raised $200 million to push this approach through pivotal trials.

The acquisition is both a clinical milestone and a corporate rescue. Sensei had just discontinued its lead cancer drug and announced a strategic review in October 2025.

Faeth's PIKTOR program combines two drugs to block PI3K, mTORC1, and mTORC2 simultaneously, providing a clinical-stage asset with Phase 2 data expected by year-end 2026. If results hold, PIKTOR could address a pathway implicated in up to 80% of cancers that has resisted single-drug approaches.

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Key Indicators

80%

Overall Response Rate

Phase 1b response rate in endometrial cancer, compared to 25-30% for chemotherapy alone

$200M

New Capital Raised

Private placement from RA Capital, Vivo Capital, and Cormorant Asset Management

11 mo

Median Progression-Free Survival

Phase 1b endometrial cancer patients; historical benchmark is 3-4 months

~80%

Cancers with PI3K Alterations

Proportion of cancers with genetic changes that could activate the PI3K pathway

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People Involved

Lewis C. Cantley

Scientific Founder, Faeth Therapeutics; Discoverer of PI3K

Scientific advisor to combined company

Anand Parikh

Co-Founder of Faeth Therapeutics; Chief Operating Officer and Director, Sensei Biotherapeutics

Leading combined company's PIKTOR program as COO

John Celebi

President and CEO, Sensei Biotherapeutics

Leading combined company post-acquisition

Organizations Involved

Sensei Biotherapeutics

Public Biotechnology Company

Acquiring entity; now advancing PIKTOR program

Nasdaq-listed oncology company that pivoted from immunotherapy development to metabolic cancer therapy through the Faeth acquisition.

Faeth Therapeutics

Private Biotechnology Company (Acquired)

Acquired by Sensei Biotherapeutics

Clinical-stage company developing multi-node therapies targeting tumor metabolism and the PI3K pathway.

RA Capital Management

Healthcare Investment Firm

Lead investor in $200M private placement

Boston-based investment firm specializing in evidence-based investing in healthcare and life sciences companies.

Timeline

January 1985 February 2026

9 events Latest: February 18th, 2026 · 7 months ago

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February 2026
Sensei Acquires Faeth, Raises $200 Million
Latest Merger

Sensei Biotherapeutics closes stock-for-stock acquisition of Faeth Therapeutics and concurrent $200 million private placement from RA Capital, Vivo Capital, and Cormorant Asset Management. The combined company will advance PIKTOR toward Phase 2 data in endometrial cancer and Phase 1b initiation in breast cancer by year-end 2026.
February 18th, 2026
October 2025
Sensei Discontinues Lead Drug, Begins Strategic Review
Corporate

Sensei Biotherapeutics halts development of immunotherapy solnerstotug, cuts 65% of workforce, and announces strategic review considering sale, merger, or wind-down.
October 30th, 2025
Faeth Announces $92 Million Total Funding
Financing

Faeth closes a $25 million strategic round, bringing total capital raised to $92 million across three funding rounds.
October 20th, 2025
March 2025
Phase 2 Trial Launches
Clinical Trial

Faeth and The GOG Foundation initiate a Phase 2 trial (GOG-3111) evaluating PIKTOR plus paclitaxel in patients with advanced or recurrent endometrial cancer.
March 12th, 2025
June 2024
Phase 1b Results Show 80% Response Rate
Clinical Data

Faeth announces Phase 1b results for PIKTOR plus paclitaxel in endometrial cancer: 80% overall response rate and 11-month median progression-free survival, versus 3-4 months historically with chemotherapy alone.
June 1st, 2024
June 2019
Faeth Therapeutics Founded
Company Formation

Lewis Cantley, Oliver Maddocks, and Anand Parikh launch Faeth to pursue multi-node PI3K pathway inhibition, hypothesizing that blocking multiple signaling nodes simultaneously could overcome the resistance and toxicity problems plaguing single-target drugs.
June 1st, 2019
May 2019
Alpelisib Becomes First PI3K Inhibitor for Breast Cancer
FDA Approval

The FDA approves alpelisib (Piqray) for PIK3CA-mutated, hormone receptor-positive, HER2-negative advanced breast cancer. The drug demonstrates efficacy but carries significant toxicity including hyperglycemia in over 35% of patients.
May 24th, 2019
July 2012
First PI3K Pathway Drug Approved for Cancer
FDA Approval

The FDA approves everolimus (Afinitor) in combination with exemestane for hormone receptor-positive, HER2-negative advanced breast cancer, marking the first approved drug targeting the PI3K/mTOR pathway.
July 20th, 2012
January 1985
PI3K Enzyme Discovered
Scientific Discovery

Lewis Cantley and colleagues at Tufts University discover phosphoinositide-3-kinase (PI3K), a finding initially met with skepticism that would later prove central to cancer biology.
January 1st, 1985

Historical Context

3 moments from history that rhyme with this story — and how they unfolded.

2005-2015

Vertex/Aurora Kinase Combination Strategy (2000s-2010s)

After single-target kinase inhibitors showed limited durability in cancer, researchers explored rational combinations blocking multiple signaling nodes. Early combination studies in chronic myeloid leukemia and melanoma demonstrated that hitting pathways at multiple points could prevent resistance emergence.

Then

Combination targeted therapy became standard in several cancers, including BRAF/MEK inhibition in melanoma.

Now

The approach validated the concept that cancer signaling pathways require multi-node blockade to achieve durable responses, providing scientific precedent for PIKTOR's strategy.

Why this matters now

PIKTOR follows the multi-node inhibition playbook that proved successful in other pathways, applying it to PI3K/mTOR—a pathway that has resisted single-target approaches for two decades.

2010-2018

First-Generation PI3K Inhibitor Failures (2010s)

Multiple PI3K inhibitors including pictilisib, buparlisib, and taselisib failed in Phase 3 trials for solid tumors. Pictilisib's Phase 2 FERGIE trial showed no significant progression-free survival improvement, attributed to toxicity-limited dosing. Buparlisib's development was halted due to psychiatric and hepatic toxicity.

Then

Several major pharmaceutical companies abandoned PI3K programs, writing off billions in development costs.

Now

The failures established that pan-PI3K inhibition was too toxic and that single isoform-selective inhibitors faced resistance from compensatory pathway activation. This shaped the scientific rationale for Faeth's multi-node approach.

Why this matters now

The history of PI3K inhibitor failures explains both why the pathway remains undertreated despite its central role in cancer and why Faeth's 80% response rate represents a potentially significant advance over prior approaches.

May 2019

Alpelisib FDA Approval (2019)

The FDA approved alpelisib (Piqray), the first PI3K inhibitor for breast cancer, based on the SOLAR-1 trial showing improved progression-free survival in PIK3CA-mutated patients. However, over 35% of patients experienced grade 3-4 hyperglycemia, and many required dose reductions or discontinuation.

Then

Alpelisib became standard of care for PIK3CA-mutated breast cancer but with significant safety management requirements.

Now

The approval validated PI3K as a therapeutic target while highlighting that single-node inhibition triggers compensatory pathway activation and substantial toxicity. This set the stage for multi-node approaches like PIKTOR.

Why this matters now

PIKTOR's multi-node strategy specifically addresses alpelisib's limitations—targeting PI3K-alpha, mTORC1, and mTORC2 simultaneously to prevent pathway escape while using dietary intervention to manage metabolic side effects.