With $24 million of series B cash in hand, Loxo Oncology Inc. disclosed more about the pipeline's lead compound in a cancer effort than the company was willing when it garnered $33 million in the series A round last October.

Frontrunner LOXO-101 is a selective inhibitor of the tropomyosin receptor kinase (Trk) family undergoing a phase I dose-escalation trial. Data suggest that Trk may behave similarly to known validated oncogenes such as ALK, RET and ROS1, behaving as a translocation partner in gene fusion events across a range a malignancies, Stamford, Conn.-based Loxo said.

By way of a deal with Boulder, Colo.-based Array Biopharma Inc. that's focused on small-molecule drugs against oncology targets – an agreement that helped Loxo to the series A – the firm is exploring several targets in preclinical development. The company expects to make known a second investigational new drug application candidate next year. Officials at Loxo could not be reached. (See BioWorld Today, July 11, 2013, and Oct. 4, 2013.)

Trk consists of a family of three receptors that sit on the cell surface known as TrkA, TrkB and TrkC, encoded by the NTRK1, NTRK2 and NTRK3 genes, respectively. Advanced sequencing methods lately have pegged Trk as implicated in diverse malignancies such as lung cancer and Spitz tumors of the skin.

Specifically, Trk may help make possible translocations: abnormal fusions of two genes that can lead to activation of a signaling pathway, and then to cancer. Other genes involved in translocation in lung and Spitz tumors include ALK, RET and ROS1 – all associated with good clinical responses in trials of other drugs in lung cancer. Scientific evidence suggests Trk may be mutated, too, in a range of cancers that include lung, colon and endometrial.

In lung cancer, targeted therapies have worked especially well, taking aim at EGFR-mutant and ALK-translocated tumors, with early data providing hope for drugs designed to attack tumors that harbor mutated ROS1, RET and bRAF genes. Trk just might join the list. Loxo intends to bring aboard diagnostic partners to help pick the right patients for trials with LOXO-101.

Another firm with strong interest in Trk is San Diego-based Ignyta Inc., which went public in March, raising $44 million for RXDX-101, one of two oral tyrosine kinase inhibitors licensed from Nerviano Medical Sciences Inc., of Nerviano, Italy. In December, Ignyta offered promising preliminary results from the ongoing phase I dose-escalation part of a phase I/II trial of RXDX-101. (See BioWorld Today, Dec. 4, 2013, and March 17, 2014.)

Ignyta plans a new, global phase I/II trial of RXDX-101 to be called STARTRK-1, a rough acronym for "Study Targeting ALK, ROS1 or TRKA/B/C." The single-arm, open-label experiment will enroll adult patients with metastatic cancer confirmed to be positive for "relevant molecular alterations," the company said, with sites in the U.S., Europe and possibly Asia. The second compound, RXDX-102, remains at the preclinical stage, and is directed to Trk family tyrosine kinase receptors, TrkA, TrkB and TrkC for multiple cancers.

The race is on. Leerink Partners LLC analyst Howard Liang wrote in a research report that Ignyta's choice to focus on Trk "may provide first-mover advantage in targeted therapy in non-small-cell lung cancer. Many compounds have activity against Trk, but only a few companies have dedicated clinical programs targeting Trk." The market opportunity in the U.S. could be as great as $2 billion, Liang estimated.

Last year, Cambridge, Mass.-based Foundation Medicine Inc. and its collaborators, the University of Colorado Cancer Center and Dana-Farber Cancer Institute, assessed cancer-related genes on tumor samples from 36 patients who were negative for activating alterations in EGFR, KRAS, ALK and ROS1 using standard clinical assays. They identified novel gene fusions harboring the kinase domain of the NTRK1 gene that encodes the TrkA receptor. The MPRIP-NTRK1 and CD74-NTRK1 fusions turned up TrkA kinase activity. The research was published in Nature Medicine.

Another company in the starting-to-grow Trk space is Tesaro Inc., of Waltham, Mass., with an ongoing phase I/II trial that designed to identify a maximum tolerated dose, define an optimal dosing schedule and evaluate safety and efficacy in tumor settings in which ALK or Trk is altered. The company continues to evaluate the fractionated 60 mg dose of TSR-011 in patients with these mutations, Liang noted, and data from experiments with that compound and others in Tesaro's lineup are expected at various medical conferences throughout 2014, including the American Society of Clinical Oncology, the Multinational Association of Supportive Care in Cancer and the European Society for Medical Oncology.

Loxo's latest round was led by New Enterprise Associates. Existing investors Aisling Capital and Orbimed Advisors LLC also participated. James Barrett, general partner of NEA, is joining Loxo's board and Sara Nayeem, a principal at NEA, is joining the board as an observer. Loxo also disclosed the appointment of Mikel Moyer as chief scientific officer.

In other financings news:

Avillion LLP, of London, said Royalty Pharma Inc., of New York, has become an investor, joining Abingworth LLP and Clarus Ventures. Royalty Pharma will be represented on the Avillion board by Jim Reddoch, vice president for research and investments at Royalty. Financial terms were not disclosed.

Celgene Corp., of Summit, N.J., disclosed its intention to offer senior unsecured notes under a shelf registration statement. The interest rate, the maturity dates and other key terms of the offering are to be determined at the time of pricing. Celgene expects to use the net proceeds from the offering for general corporate purposes. Merrill Lynch, Pierce, Fenner & Smith Inc., Credit Suisse Securities (USA) LLC, Goldman, Sachs & Co. and Morgan Stanley & Co. LLC are acting as joint bookrunning managers.

Invivo Therapeutics Holdings Corp., of Cambridge, Mass., priced an underwritten public offering of about 12.2 million shares of common stock and warrants to purchase up to an aggregate of about 6 million shares of common stock at $1.15 per share of common stock and $0.00001 per warrant. The warrants have a per share exercise price of $1.43, 125 percent of the public offering price of the common stock, are exercisable immediately, and expire five years from the date of issuance. Invivo has granted the underwriters a 45-day option to purchase up to about 1.8 million shares of common stock and/or additional warrants to purchase up to 913,250 additional shares of common stock to cover overallotments. The offering is expected to close on or about May 9, 2014. The gross proceeds of the offering are expected to be about $14 million.