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Opening New Frontiers By Advancing The Promise of PI Signaling Pathways

Petra Pharma at a glance

Petra is a leading clinical-stage pharmaceutical company developing a diverse portfolio of novel therapies that modulate phosphoinositide (PI) signaling pathways for the treatment of cancer.

PI pathways regulate fundamental processes of cellular growth and metabolism. The importance of PI signaling in human health is underscored by the many diseases that arise from PI pathway dysregulation. PI-modifying enzymes are among the most frequently mutated proteins in cancer, yet developing drugs that successfully disrupt the cancer-causing signaling in PI pathways has proven a challenge.

The biology involved in PI signaling pathways is incredibly complex. Armed with a refined understanding of these pathways, building on more than 30 years of pioneering research by its co-founders Dr. Lewis Cantley and Dr. Nathanael Gray, Petra is developing therapeutic agents designed to inhibit specific PI enzymes by targeting key steps, mutations and branches in the PI pathways to yield effective and safe cancer therapies.

Investors

AbbvieAlexandriaARCH Venture PartnersCapital CorpInnovate NY FundJohnson and Johnson Innovation LabsLillyPartnership for New York CityPfizerWatson FundWuXi AppTech

Products

Petra is exploring new frontiers in PI signaling pathways to introduce next-generation lipid kinase inhibitors that offer the potential to address the many tumors characterized by PI pathway dysregulation. Armed with a refined understanding of these pathways, Petra is advancing a diverse portfolio of therapies for the patients most in need of them.

Click the specific program below to find out more information about our therapeutic candidates and the cutting-edge science behind them.

Program

Discovery

IND-enabling

Ph 1

Ph 2

Ph 3

PETRA 06 (Serabelisib)

  • PETRA 06 is the lead drug in Petra Pharma's PI3K program, which specifically targets one of the most frequently mutated signaling pathways in cancer while simultaneously defeating the “glucose/insulin feedback loop” that has historically hindered the effectiveness of such drugs.
  • Leveraging the research of company co-founder Dr. Lewis Cantley, PETRA 06 combines an alpha-specific PI3K inhibitor (serabelisib) with a sodium-glucose co-transporter 2 (SGLT2) inhibitor, a well-established class of diabetes drug. Results from animal studies show that this approach has the potential to substantially increase the anti-tumor activity of PI3K inhibitors.
  • Petra plans to initiate a Phase 1b/2 study in 2019 focused on patients with advanced PIK3CA-mutated solid tumors.

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petra06program

PETRA 06 (Serabelisib)

  • Petra Pharma co-founder Dr. Lewis Cantley uncovered the signaling enzyme PI3K in 1988. It is one of the most frequently mutated signaling pathways in cancer. Yet few drugs have been developed that successfully disrupt the oncogenic signaling in this pathway.
  • This is complex biology, requiring a deep understanding of PI signaling pathways to pinpoint the right targets, the right steps and the right mutations to yield effective and safe therapies.
  • Dr. Cantley and his collaborators discovered that inhibiting the PI3K pathway triggers a jump in blood glucose levels followed by a spike in insulin levels. This is known as a glucose/insulin feedback loop.
  • This glucose/insulin spike reactivates the PI3K in cancerous tumors and diminishes the cancer-killing effect of therapies targeting this signaling pathway.
  • Yet Dr. Cantley and his collaborators made another discovery. Preventing the glucose/insulin spike, or at least controlling it, dramatically enhances the anti-tumor efficacy of PI3K inhibitors in animal models1.

1 Nature. 2018 Aug; 560(7719): 499 -503.

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petra06science

PETRA 03

  • PETRA 03 is the next-generation of Petra Pharma's PI3K program. Petra is pioneering a novel approach to selectivity target the mutant forms of PI3K, one of the most frequently mutated signaling pathways in cancer.
  • PETRA 03 includes mutant-specific PI3K inhibitors with selectivity for common mutations over wild-type PI3K, avoiding the glucose/insulin feedback loop.
  • While controlling the glucose/insulin feedback loop is highly desirable, avoiding the glucose/insulin feedback loop may be optimal.
  • PETRA 03 is being developed to specifically target advanced solid tumors with mutations of the PIK3CA gene.

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petra03program

PETRA 03

  • A refined understanding of PI signaling pathways is needed to pinpoint the right targets, the right steps and the right mutations to yield effective and safe therapies.
  • PI3K is one of the most frequenty mutated pathways in cancer. Yet few drugs have been developed that can successfully disrupt the oncongenic signaling of this pathway, and those that do exist provide patients little benefit.
  • Petra’s co-founder Dr. Lewis Cantley and his collaborators discovered that inhibiting the PI3K pathway triggers a spike in blood glucose levels followed by a spike in insulin levels that limits the effectiveness of such therapies.
  • PETRA 03 includes mutant-specific PI3K inhibitors with selectivity for common mutations over wild-type PI3K, avoiding the glucose/insulin feedback loop.
  • PETRA 03 is designed on the premise that while controlling the glucose/insulin spike is desirable, avoiding it altogether is optimal.

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petra03science

PETRA 01

  • The lead candidate in Petra’s PIP4K2 program, PETRA 01 targets an entirely different PI pathway that could address both hematologic cancers and solid tumors.
  • Inhibiting PIP42K impacts late-stage tumor autophagy, a regenerative feature that protects cancer cells, allowing them to survive and proliferate.
  • The initial focus for PETRA 01 is leukemia, lymphoma and other hematologic cancers, which have displayed a high rate of sensitivity to PIP4K2 in pre-clinical studies.
  • Several types of solid tumor cell lines are also sensitive to PIP4K2 inhibition.

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petra01program

PETRA 01

  • Petra is exploring new frontiers in PI signaling pathways to introduce “next-generation” lipid kinase inhibitors that offer the potential to address the many tumors characterized by PI enzyme mutations.
  • Petra has developed highly potent, selective, and drug-like inhibitors of PIP4K2 enzymes, targeting the regenerative feature known as late-stage autophagy that enables cancer cells to survive and proliferate.
  • Studies show that many tumors are autophagy-dependent, which means survival depends on the ability to use the autophagy pathway to replenish nutrients2.
  • Inhibiting PIP42K also deprives certain cancer cells of the ability to withstand chemotherapy and other therapeutic stresses.

2 Int J Mol Sci. 2017;18(6):1279.]

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Petra01MOA