Tocagen Inc.

Tocagen develops cancer-selective gene therapies. Lead product candidates Toca 511 and Toca FC are being developed together to treat recurrent high grade glioma and the US FDA recently granted a breakthrough therapy designation for the combination in that indication. Toca 511 delivers a gene called cytosine deaminase to cancer cells to infect the tumor and Toca Fc – the inactive prodrug 5-fluorocytosine (5-FC) – is converted to the active chemotherapy drug 5-FU to kill the infected areas of the tumor, the surrounding cancer cells and immunosuppressive myeloid cells, activating the immune system in the process to increase the tumor-killing effect. Tocagen recently completed patient enrollment in its registrational Phase II/III clinical trial and expects to report top-line results in the hard-to-treat brain cancer during the first half of 2018. (Also see "Tocagen Aims Double Barrels At Glioma" - Scrip, 1 February, 2017.)

CytomX Therapeutics Inc.

CytomX is using its Probody technology platform to develop targeted cancer immunotherapies with reduced toxicity. The technology involves amino acid-masking of the targeting end of an antibody or any other therapeutic modality. That mask comes off only in the presence of tumor-specific proteases, so the therapy is delivered directly to cancer cells. A recently initiated Phase I/II trial is testing CX-072, a PD-L1-targeting Probody therapeutic, as monotherapy and in combination with Bristol-Myers Squibb Co.'s Yervoy (ipilimumab) or Roche's Zelboraf (vemurafenib) in various cancers. (Also see "Pipeline Watch: Evolocumab, Roxadustat And SB-204, Top-line Results" - Scrip, 6 February, 2017.) The company, which went public in October 2015, has inked several discovery and development partnerships. (Also see "Is the Biotech IPO Window Closing?" - Scrip, 22 October, 2015.) Also of note, Chief Medical Officer Rachel Humphrey supervised the Yervoy development program at Bristol-Myers from early R&D through one year post-approval.

Trillium Therapeutics Inc.

Trillium is developing immunotherapies that target CD47, but unlike its competitors the company's product candidates are not monoclonal antibodies. Lead drug candidate TTI-621 is a Signal Regulatory Protein (SIRP) alpha fusion decoy receptor. The drug targets the SIRP alpha receptor on macrophages, which are found in the tumor microenvironment, to turn on the "eat me" signal within the macrophages – a signal that CD47 blocks. TTI-621 is being evaluated in two Phase I trials, including a study in hematologic malignancies testing the drug as a monotherapy and in combination with other therapies. The second study in solid tumors enrolled its first participant at the end of January; the company is testing an intratumoral injection of TTI-621 in that trial. (Also see "Trillium Looks To Lead The Immuno-Oncology Pack In CD47 Inhibition" - Scrip, 11 October, 2016.)

Xencor Inc.

Xencor uses its XmAb Antibody Engineering Platform to engineer monoclonal antibodies with altered Fc domains as a means for improving function and performance. The technology is a "plug-and-play" platform that can be used to alter almost any antibody, which has resulted in several discovery and development collaborations with big pharma and large biotech partners. Xencor executed a deal last year with Novartis AG that could be worth as much as $2.5bn. (Also see "Novartis Deal Gives Xencor $150m Up Front, Up To $2.41bn In Milestone Fees" - Scrip, 28 June, 2016.) Johnson & Johnson's Janssen subsidiary and MorphoSys AG each have Xencor-engineered IO antibodies in Phase II/III trials and Boehringer Ingelheim GMBH has two IO molecules based on Xencor's technology in Phase I. Xencor also has two wholly-owned bi-specific antibodies that bind to T cells and antigens in early clinical trials. The company's next clinical bi-specific antibody programs in the IO space will target cells in the tumor microenvironment. (Also see "Xencor's Coming Share Issue To Help Fund Immuno-Oncology Pipeline" - Scrip, 2 December, 2016.)

Poseida Therapeutics Inc.

San Diego-based Poseida was spun out of Transposagen Biopharmaceuticals to use genome-editing technology in the development of chimeric antigen receptor T cell (CAR-T) therapies for cancer – including programs in collaboration with Johnson & Johnson's Janssen subsidiary – as well as gene therapies for other diseases. The company plans to submit an investigation new drug (IND) application for its lead CAR-T therapy this year with the intention of dosing the first patient in its first clinical trial during the fourth quarter. Poseida completed its Series A round for up to $30m in early 2015. (Also see "Startups Stand Out As 13 Biotechs Raise More Than $409m" - Scrip, 18 December, 2015.)

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