Send in the Pentarins: Tarveda raises $30M Series D

Like deadly paratroopers descending from the skies, Tarveda’s Pentarin drug conjugates are designed to infiltrate dense tumors, triggering a controlled cell death as they are internalized or bound. It’s an ADC variation that’s gaining momentum and cash.

Drug delivery ADC antibody drug conjugates

In a past life, Tarveda Therapeutics was called Blend Therapeutics. Founded in 2012, the company’s pipeline was full of potential but it lacked a clear focus. It was, for lack of a better word, a blend of different scientific programs.

By 2015, it was beginning to reimagine itself. Certain assets were sold and the company doubled-down on its prized Pentarin oncology platform. In January 2016, Tarveda rebranded and raised a $38 million Series C to forge a new path.

On Thursday, the company announced a subsequent $30 million Series D, led by Versant Ventures, a first-time investor. Existing investors New Enterprise Associates, Novo A/S, NanoDimension and Flagship Pioneering also got on board.

In a phone interview, Tarveda President and CEO Drew Fromkin was energized about the company’s high-potential drug conjugate platform.

Fromkin describes Pentarins, the candidates born out of the platform, as potent and selective miniaturized conjugates. They’re a novel take on the more well-known antibody drug conjugates (ADCs), such as FDA-approved Kadcycla

As with ADCs, Pentarins combine the strengths of multiple compounds, bound by a chemical linker molecule. There’s a targeting mechanism, which guides the conjugate to a certain receptor (ideally expressed by cancer cells); and a payload, a highly cytotoxic compound that delivers the punch.

“While we draw from the value that we’ve seen from the ADC revolution and what ADCs do in terms of solid tumors and blood cancers, we do also feel like there are a number of deficits,” Fromkin said. 

The largest of which is the size of traditional ADCs. Fromkin notes that ADCs are typically 50 times larger then Pentarins, primarily due to the antibody component. This limits the ability of ADCs to penetrate tissues.

Pentarins bypass the large molecules and employ a different cancer-seeking design. Tarveda’s lead asset PEN-221, for example, is a peptide ligand that selectively targets the somatostatin receptor SSTR2, preferentially expressed by certain cancers.

Large molecules, such as ADCs, can also stay in the patient’s system for weeks, increasing the risk of side effects as they move about with their highly potent payload. Small molecules suffer from the opposite problem — they can get cleared from the body too quickly to take effect.

Pentarins are designed as a happy medium.

“With our half-life and our targeting and our size, we only want to be in the body in terms of the peripheral tissues on the order of hours,” Fromkin stated.

The drug conjugates are designed to be bound or absorbed by the tumor tissue. This accumulation happens in a matter of hours, limiting the exposure of healthy cells. From there, the chemical linker molecule slowly releases the cytotoxic payload over a period of days, ultimately triggering cell death.

The third major challenge affecting nearly all precision oncology drugs is finding a suitable target. There is no 100 percent cancer-specific protein. Some cancer cells won’t express that protein; some healthy cells will. Companies aim to find a workable compromise.

Tarveda is exploring different receptor targets and also playing around with the payloads it attaches to its conjugates.

PEN-866, for example, targets heat shock protein 90 (HSP90). It is found in many healthy cells, but the binding profile of the protein changes when the cells are malignant. PEN-866 targets this modification only.

The drug appears to penetrate healthy tissues, Fromkin said, but then diffuse back out if it isn’t bound.

In its first proof-of-concept study, the therapeutic payload of PEN-866 will be SN-38, a topoisomerase inhibitor. While topoisomerase is a validated therapeutic target, the drugs are very toxic. Tarveda hopes it can minimize the side effects by delivering the drug much more selectively.

The Pentarin platform can generate countless drug conjugate combinations. On the other hand, there are many unknowns and variables with a three-part synthetic drug. And the company is early-stage.

With its latest funding, Tarveda plans to complete Phase I dose-escalation and safety studies for PEN-221, targeting SSTR2 in neuroendocrine and small cell lung cancers. All going well, the cash would allow the company to follow up with a Phase 2A study of the same drug. The company will also fund Phase I dose-escalation studies of PEN-866 and further develop additional Pentarin candidates.

Watch this space. With a singular focus on the Pentarin platform, Tarveda could go far.

Photo: njpPhoto, Getty Images