Tyg Oncology Ltd. and Oncoqr ML GmbH are relative newcomers to the field of cancer immunotherapy but their platforms are not. What's different now is that Tyg's lead vaccine candidate, TYG100, which targets gastrin (G17) for the treatment of pancreatic and other gastrointestinal (GI) cancers, is powered by the S-TIR technology platform – originally developed by S-target Therapeutics GmbH to treat severe allergic diseases and out-licensed for oncology uses to Oncoqr.

The path to a first-in-human trial for TYG100 has been fraught with twists and turns, but the interconnected companies believe they now have running room to accelerate the candidate's development.

Vienna-based Oncoqr is a start-up founded in 2013 by pharma veterans Christof Langer and Geert Mudde to develop next-generation checkpoint immunotherapies targeting oncology, autoimmune and infectious disease indications. Langer spent more than a decade at Baxter Bioscience before founding S-target in 2010. Following his start at the Swiss Institute for Asthma and Allergy Research, Mudde moved to biopharma as deputy head of immunology at the Novartis Research Institute in Vienna, followed by tenure at the Parke Davis Research Institute in Fresnes, France, at Ingenium Pharmaceuticals AG, of Martinsried, Germany, and at Igeneon AG, of Vienna, before also joining Baxter Bioscience. Mudde subsequently co-founded the biotech company F-star GmbH, and, with Langer, S-target.

In 2013, Oncoqr became a joint venture partner in the formation of London-based Tyg, along with a trio of former Aphton Corp. executives, including Fred Jacobs, Aphton's chief financial officer, who serves as Tyg's CEO. Philadelphia-based Aphton spent more than two decades advancing technology designed to neutralize gastrin hormones for the treatment of GI cancers. The company raised more than $200 million, acquired Igeneon, attracted partners such as Smithkline Beecham plc (now part of Glaxosmithkline plc) and Sanofi Pasteur (now part of Sanofi SA) and reported promising data for its lead candidate, Insegia, but the therapy failed to meet the primary endpoint in a pivotal phase III trial in the lead indication in pancreatic cancer. Aphton's story unraveled from there, forcing the company into bankruptcy in 2006. (See BioWorld Today, June 22, 1998, Oct. 31, 2003, Dec. 16, 2004, Feb. 16, 2005, and May 25, 2006.)

Along the way, however, Aphton collected valuable data from 22 trials that enrolled more than 1,000 patients, including phase III studies of Insegia as a monotherapy and in combination with gemcitabine.

"For individuals who were high responders, there was a positive correlation with survival and there was a lot of promise," Jacobs told BioWorld Today. "But there weren't enough high responders and we were using diphtheria toxoid to deliver the antigen. We didn't get a great response."

'A trickle of water to Niagara Falls'

Jacobs and the Aphton team didn't give up on the approach, however, founding Nottingham, U.K.-based Astrimmune Ltd. to shepherd the gastrin hormone neutralization technology. The work attracted the attention of Oncoqr, which led to the Tyg joint venture. Oncoqr's lead asset, TYG100 (OQR100), was out-licensed to Tyg, which filed for patent protection in 2014. The therapy also has FDA orphan drug designation in pancreatic cancer.

"Oncoqr had this beautiful S-TIR technology platform that had achieved checkpoint control over the immune system," Jacobs said. "We were looking for a better rocket to deliver our warhead. We were able to use our antigen with the S-TIR technology platform, and we've achieved success."

The "warhead" combines multiple elements designed to enhance uptake of the vaccine, serve as an intrinsic antigen and bind to the immunogenic portion of the drug, which activates tumor-specific T and B cells. The technology allows the delivery of multiple antigens with the same vehicle, according to Jacobs.

Success is still preclinical: Tyg showed that it could produce therapeutic levels of gastrin-neutralizing antibodies in nonhuman primates with a single shot of TYG100 – importantly, with no serious adverse events. Redesigning the vaccine based on the S-TIR platform increased the difference in immunogenicity exponentially, Jacobs said, comparing the difference in response from "a trickle of water to Niagara Falls."

Tyg and Oncoqr plan to publish findings from the dose-ranging study in nonhuman primates in a peer-reviewed journal.

Tyg and Oncoqr also said last week they will seek to develop additional therapeutic vaccines against GI cancers, and Tyg was awarded exclusive right to exploit the S-TIR technology for other forms of gastrin and related GI targets. Jacobs declined to provide additional details.

Oncoqr has three additional vaccine candidates based on S-target's human-specific S-TIR technology platform, designed to enable a patient's immune system to generate a strong immune response against non-immunogenic targets, especially tumor-associated antigens. The company's second program, OQR200, is a candidate against HER2.

In the meantime, Tyg is responsible for completing toxicology and manufacturing work on TYG100 and advancing the candidate into a first-in-human study, which could begin in about two and a half years, Jacobs said. With just nine employees, Tyg is seeking to raise a private round of about £5 million (US$7.2 million) to fund the work, and the company is not averse to the notion of crowdfunding, Jacobs said.

Long term, Tyg will seek fast track approval from the FDA, which could allow the company to submit regulatory filings following multicenter phase II studies.

"We'll consider all options" to advance TYG100, Jacobs said. Although the company hopes to attract a pharma partner, it's also willing to go alone.

"The faster we can get to the clinic, the faster we can put this therapy into the hands of clinicians to treat patients," Jacobs said. "This is our product to bring to market. We think it's a relatively easy product to manufacture, and it's safe and well tolerated, so we think the regulatory hurdles will be surpassed fairly easily."