Michael Engsig, CEO of Oslo, Norway-based Vaccibody AS, said the company’s deal with Roche Holding AG lets his firm “fully set in motion” the plan to explore infectious diseases as well as cancer, and Chief Scientific Officer (CSO) Agnete Fredriksen pointed out that “an exceptional cross-functional team” has been put in place to get the job done.

Vaccibody signed the new contract with Basel, Switzerland-based Roche’s Genentech arm to develop and sell DNA-based individualized neoantigen vaccines for cancers. The tie-up brings as much as $715 million for Vaccibody, including up-front and near-term payments of $200 million and potential milestone-based rewards of up to $515 million, plus low, double-digit tiered royalties. Together the duo will move forward Vaccibody’s DNA-based neoantigen vaccine, VB10.NEO, in the U.S. and Europe.

Vaccibody will handle development through the end of phase Ib trials, with Genentech taking the ball afterward. VB10.NEO targets encoded antigens to antigen-presenting cells and can be produced on-demand, in accordance with the neoantigen profile of an individual patient. The first work, done “in close collaboration with Genentech,” will also include a research, bioinformatics and manufacturing tie-up, Fredriksen said. “As this is a personalized cancer vaccine, there are a lot of steps involved.”

Michael Engsig, CEO, Vaccibody

Underway is VB N-01, a phase I/IIa study testing VB10.NEO when combined with San Francisco-based Nektar Therapeutics Inc.’s bempegaldesleukin (bempeg, NKTR-214) immunotherapy in patients with locally advanced or metastatic melanoma, non-small-cell lung carcinoma (NSCLC), clear renal cell carcinoma (RCC) as well as urothelial cancer (UC) or squamous cell carcinoma of the head and neck (SCCHN). Positive first results have turned up, Vaccibody said, with VB10.NEO inducing strong tumor-specific immune responses. Interim data suggest a clear link between selection of high quality neoepitopes, generation of strong neoepitope-specific CD8+ T-cell responses, and clinical responses. The arrangement with Nektar was entered in September 2018, and the first patient with advanced SCCHN was dosed in August of this year.

Vaccibody has another compound in the clinic: VB10.16, a phase II-stage vaccine against human papillomavirus 16-linked cancer. It’s partnered with Basel, Switzerland-based Roche, too, and is being tested with Roche’s immune checkpoint inhibitor, Tecentriq (atezolizumab). During a conference call with investors, Engsig said the company will seek more collaborations, including those for earlier-stage programs in the pipeline. “Vaccibody is always looking for partners, that’s for sure,” he said, noting that the features of the platform let the firm “basically construct this kind of agreement in a way that will allow the company to continue exploring its technology” alone and with partners, by carefully regulating the intellectual property involved.

Agnete Fredriksen, president and chief scientific officer, Vaccibody

CSO Fredriksen said Roche is “by far the partner of choice” for VB10.NEO. Regarding other cancer and infectious disease indications, she said she “cannot share [specifics] at the moment. We have generated a lot of knowledge on selecting the optimal antigens,” and exploration is ongoing.

As Vaccibody broadens its research efforts, the company plans to maintain headquarters in Norway. “We will, of course, require additional talents in the company,” Engsig said. “Where those talents come from, time will show.” Vaccibody has applied for a listing of its shares on the Norwegian trading platform Merkur Market, owned and operated by Oslo Bors (the Oslo stock exchange). The first day of trading on Merkur is expected to be on or about Oct. 7.

Nektar’s bempeg represents an intriguing prospect in other quarters. It’s a recombinant form of interleukin-2 conjugated to multiple polyethylene glycol chains, meant to work by targeting CD122 receptors found on the surface of CD8+ effector T cells and NK cells. The candidate is closely watched. With New York-based Bristol Myers Squibb Co., Nektar is trying bempeg in a dose-escalation and cohort expansion study called Pivot-02 in combination with the latter’s Opdivo (nivolumab) and other cancer therapies in patients with select solid tumors. SVB Leerink analyst Daina Graybosch said in an Aug. 14 report that company backers “are unlikely to engage with the parade of early-phase data Nektar has planned for this fall, as the story remains squarely” on bempeg.

Pivot-02 is a complicated, four-part experiment. In part 1, bempeg will be administered with Opdivo; with Opdivo with or without various chemotherapies in part 2; and with Opdivo and Yervoy (ipilimumab, Bristol Myers Squibb Co.) in parts 3 and 4. In part 1, the recommended phase II dose (RP2D) of the Opdivo combo will be determined. In part 2, bempeg plus Opdivo at the RP2D will be evaluated as first-line therapy and/or as second- or third-line therapy in patients with melanoma, RCC, NSCLC, UC, metastatic breast cancer and colorectal cancer. Also in part 2, the RP2D of bempeg with Opdivo and various chemos and regimens in select cohorts of NSCLC patients will be figured out. In part 3, several different regimens of the triplet combo of bempeg plus Opdivo and Yervoy will be tested in patients with RCC, NSCLC, melanoma and UC. In part 4, the safety and efficacy of the triplet combo will be evaluated further in select patients with RCC, NSCLC, melanoma and UC.

“While updated PIVOT-02 data for bempeg plus Opdivo in melanoma at the Society for Immunotherapy of Cancer meeting in November may spark a bit of interest, we think investors have already made up their mind about the strength of the complete response rate signal,” Graybosch said. “Nektar management also promised landmark survival data, and we will be closely comparing landmark rates to those seen with anti-PD-1 alone, as we find median progression-free survival to be particularly misleading in this setting.”