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Nykode Therapeutics Pursuing Fast-to-Market Strategy for HPV16-Targeted Cancer Vaccine

Microscope image of cervical cancer

NEW YORK – Nykode Therapeutics is pursuing a fast-to-market strategy for its HPV16-targeted vaccine in advanced cervical cancer, but the firm believes its vaccines could potentially treat pre-malignant to late-stage disease in multiple tumor types.

The Oslo, Norway-based company, formerly known as Vaccibody, was founded in 2006. It develops targeted immunotherapies on its Vaccibody technology platform. A Vaccibody protein comprises three segments: a targeting unit that directs the protein to the immune system's antigen presenting cells, an antigenic unit containing epitopes specific to the disease, and a dimerization unit joining the other two segments. The technology is agnostic to the delivery modality and can be adapted to utilize DNA, RNA, or proteins.

Nykode is currently developing vaccine candidates that will be delivered in plasmid DNA form, but according to Nykode CSO Agnete Fredriksen, the company plans to also investigate different formats in the future.

Fredriksen said that what distinguishes Nykode's approach from that of other vaccine developers is that it is specifically directed to antigen-presenting cells that mediate T-cell response by displaying antigens bound to major histocompatibility complex proteins on the cell surface. When the antigen alone is administered without that targeting system, "there is a high likelihood that [many] of the antigens are not reaching [the antigen-presenting cells], which are the ideal cell type to initiate an immune response," Fredriksen explained.

Nykode has further refined the method so that researchers can use different targeting units in the Vaccibody construct and optimize the response of different types of T cells, such as helper T cells, killer T cells, or even regulatory T cells. The company is investigating the latter in its inverse vaccine program, for suppressing overactive immune response in autoimmune disease.

Nykode is advancing its lead program, an off-the-shelf therapeutic cancer DNA vaccine targeted against HPV16-driven malignancies dubbed VB10.16, in three clinical trials in advanced cervical cancer, head and neck cancer, and locally advanced cervical cancer.

HPV16-positive cervical cancer is the fourth most common cancer in women worldwide, and the fourth leading cause of cancer-related death. The incidence of cervical cancer is expected to increase globally despite the availability of prophylactic HPV vaccination. That's due in part to the fact that the rollout of HPV vaccines hasn't been ideal and to changing lifestyles, Nykode CEO Michael Engsig said at the JP Morgan Healthcare Conference in January. Over the next 10 years, Engsig said, Nykode expects to see an "increasing, addressable patient population" for VB10.16.

In the Phase IIa C-02 trial, Nykode is evaluating the safety and efficacy of multiple doses of VB10.16 with Roche's PD-L1 inhibitor Tecentriq (atezolizumab) in patients with recurrent or metastatic, nonresectable, HPV16-positive cervical cancer. Patients must have failed or be ineligible for systemic chemotherapy, radiotherapy, or other standard therapies to participate in the study. Patients are receiving a total of 11 intramuscular injections of the vaccine for up to 48 weeks and Tecentriq every three weeks.

In interim results from the C-02 trial as of December 2022, 29 percent responded to the vaccine-Tecentriq regimen. Median progression-free survival was 6.3 months, and median overall survival was not reached. Engsig pointed out that checkpoint inhibitor monotherapies in the same setting have overall response rates ranging from 16 percent to 19 percent and shorter median progression-free and overall survival.

For example, in the Phase II Skyscraper-04 trial, PD-L1-positive recurrent cervical cancer patients on Tecentriq monotherapy had a median progression-free survival of 1.9 months and median overall survival of 10.6 months. Similarly, in the Phase II Keynote-158 basket trial, advanced cervical cancer patients treated with Merck's PD-1 inhibitor Keytruda (pembrolizumab) had median progression-free survival of 2.1 months and median overall survival of 11 months.

Engsig also highlighted results from a clinical trial of the tissue factor-directed antibody-drug conjugate Tivdak (tisotumab vedotin), marketed by Pfizer and Genmab. In the Phase III InnovaTV 301 trial, patients with recurrent or metastatic cervical cancer on Tivdak had median progression-free survival of 4.2 months and median overall survival of 11.5 months.

Nykode is expecting that Tivdak will likely be VB10.16's main competitor in the cervical cancer market. Engsig said when the data are mature, the company is expecting median overall survival for VB10.16 will be more than 25 months, or about double survival the time compared to how long patients on average live on checkpoint inhibitors or Tivdak. "On the back of these positive data we have devised a growth strategy for [VB10.16] where we will continue on a fast path to market in the advanced cervical cancer setting," Engsig noted.

To accomplish that, Nykode has begun the Phase II C-04 trial. In that potentially registrational trial, Nykode is evaluating VB10.16 alone or in combination with Tecentriq as a second-line therapy in the relapsed and refractory HPV16-positive cervical cancer setting. Investigators will enroll patients who have progressed on first-line Keytruda and chemotherapy, with or without Roche's VEGF inhibitor Avastin (bevacizumab). The company expects to finalize enrollment for C-04 by the end of the year and report interim data in the middle of 2025. Engsig said Nykode has discussed the trial with the US Food and Drug Administration and is hoping to file for accelerated US approval as soon as 2027 and launch VB10.16 in late 2027 or early 2028.

If this strategy proves successful in the cervical cancer market, Nykode hopes to advance VB10.16 in HPV16-positive head and neck cancer and in locally advanced cervical cancer. In the Phase I/IIa C-03 trial, researchers are testing VB10.16 as a therapy for recurrent or metastatic HPV16-positive head and neck squamous cell carcinoma in combination with Keytruda, which is currently the standard-of-care therapy for patients with previously untreated advanced PD-L1-positive HNSCC.

Lastly, Engsig said Nykode is in the planning stages for another trial of VB10.16, dubbed C-05, in the adjuvant cervical cancer setting, "which of course represents an even larger commercial opportunity."

Ultimately, the company's goal is to prove its vaccines prevent cancer in addition to treating it. "At the core of our company, you will find a mission to be able to provide cancer vaccines to patients at the precancerous stage in the future," Engsig said in an interview. "That's what we are dreaming about." He envisions a future where, as soon as a patient is found to have a risk factor or precancerous cellular changes, there will be a vaccine available that prevents cancer from developing.

Beyond its HPV16-directed vaccines, Nykode has partnered with Roche subsidiary Genentech to develop a neoantigen cancer vaccine, VB10.NEO. Within this program, Nykode uses a proprietary algorithm to select 20 epitopes for the vaccine based on tumor mutations specific to the patient. Unlike other players on the market focusing on developing mRNA-based neoantigen vaccines, such as Moderna, Nykode is using DNA as the modality for its vaccine. 

Nykode has completed a Phase I/IIa N-01 trial of VB10.NEO in combination with Nektar Therapeutics' bempegaldesleukin immunotherapy and has begun the Phase Ib N-02 trial of VB10.NEO with Tecentriq in collaboration with Genentech.

In the N-01 trial, Nykode saw both broad T-cell responses and durable neoantigen-specific T-cell responses. Engsig said the "very consistent, slow buildup of a sustained immune response on treatment and post-treatment … tells us we have a technology that is very applicable not only in the recurrent metastatic setting but also in the early-stage, locally advanced setting across tumor types."

Nykode will get the chance to test that hypothesis in the N-02 trial. Genentech and Nykode are evaluating the safety, tolerability, antigen-specific immune response, and preliminary anti-tumor activity of VB10.NEO with Tecentriq in patients with locally advanced and metastatic tumors, who have progressed after at least one line of standard therapy or who have been unable to tolerate standard therapy.

Under the worldwide licensing and collaboration agreement with Genentech, signed in 2020, Nykode received $200 million upfront and is eligible for $515 million in additional payments and milestones, plus tiered low double-digit royalties.

At the end of Q4 2023, Nykode had $162.6 million in cash. Engsig said the firm has enough funds to see the company through its near-term R&D goals for VB10.16, VB10.NEO, and other programs.