G1 Therapeutics Inc.'s $33 million in series B money gives the firm "flexibility to hang onto [the lead program] and continue to move it further into development on our own," said CEO Mark Velleca. "We'll certainly keep interested parties informed of our progress, but it's great to have the resources to move the asset forward" into phase Ib/IIa experiments without a partner.

That asset is G1T28, described as a highly potent and selective cyclin-dependent kinase (CDK) 4/6 inhibitor being tested as an oral antineoplastic agent and as an intravenous (I.V.) bone marrow chemoprotectant. As a mechanism of action, CDK4/6-targeting made headlines earlier this week with the FDA's approval of New York-based Pfizer Inc.'s Ibrance (palbociclib) for use in advanced or metastatic breast cancer. Candidates taking aim at CDK4/6 are in the works by Novartis AG, of Basel, Switzerland, and Indianapolis-based Eli Lilly and Co., and "each has its weaknesses," Velleca said. "We think we have an opportunity to be best in class." (See BioWorld Today, Feb. 4, 2015.)

"What sets us apart from the three competitors is that we have an I.V. drug and quite a bit of experience understanding how it can be used as a bone marrow chemoprotectant," thanks to work done by G1's founders, Velleca said, who exploited the finding that CDK4/6 is "not just important to drive tumor cell proliferation – it's also a critical regulator of hematopoietic stem cell proliferation. Their idea is very simple: Pause the division of the cells in the bone marrow while cytotoxic chemotherapy is on board. When the chemo washes out and is done, our drug is no longer present and the bone marrow cells recover much more rapidly."

He called the preclinical data "very impressive. We just found out we have an oral talk at the American Association of Cancer Research meeting [in April], where we will be presenting these preclinical data." Dosing has been completed in the phase Ia trial with the I.V. therapy. "In the second quarter of this year, we'll start a trial in patients who have small-cell lung cancer [SCLC], which is CDK4/6-independent, so we won't be protecting the tumor from chemotherapy, just the bone marrow," Velleca said. The series B cash will let the firm "generate very robust proof-of-concept data in that SCLC" trial.

Further work is slated to start in the second quarter of this year, with the oral version of the compound to be tested in the fourth quarter against an indication yet to be disclosed.

"We can certainly get the SCLC trial completed, and [get] well into the oral trial," Velleca told BioWorld Today, estimating the money on hand will last for about two years. "In 2012, the company really got started with a seed financing," when G1 had "a handful of lead compounds," he said. "Those were expanded upon, and ultimately a clinical candidate was chosen," a move enabled by the $12.5 million series A round in October 2013. "The company's made tremendous progress and been very capital-efficient," he said. (See BioWorld Today, Nov. 6, 2012.)

G1 is ideally positioned, given "where cancer therapeutics are going," Velleca said. "Basically all patients are going to have some form of genomic profiling done, and it will be readily known what their CDK4/6 status is. If they happen to be patients with a tumor that's driven by CDK4/6, they're candidates for the oral drug. If not, and they're getting myelosuppressive chemo, which many of them do, they'd be candidates for the I.V. drug."

The Research Triangle Park, N.C.-based company has dosed more than 40 patients with the drug, and "there are some emerging clinical data," which also will be shared at the late May/early June American Society of Clinical Oncology meeting in Chicago, he said.

"This is a therapy that's going to be combined with other targeted drugs, so the cleaner the compound that you have – whether that's from a selectivity standpoint, cardiac safety or pharmacokinetics/pharmacodynamics – the better it's going to combine," Velleca said. "Ultimately, we'll have to prove that in the clinic, and now we have the resources to do it."

Lead investors in the series B are Eshelman Ventures and RA Capital Management, joined by new backers Lumira Capital and Boxer Capital of Tavistock Life Sciences, as well as the company's existing investors Hatteras Venture Partners, Medimmune Ventures and Mountain Group Capital. Fred Eshelman, founder of Eshelman Ventures, and Peter Kolchinsky, managing general partner of RA Capital, have joined G1's board.