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Genentech, BioNTech Deal Pushes Personalized Cancer Vaccines Toward Market


NEW YORK (GenomeWeb) – With a $310 million deal announced last month, Genentech has dedicated itself to helping advance German biotech firm BioNTech's proprietary method for designing personalized cancer vaccines.

The move reflects an ongoing shift for this type of approach — which involves comprehensively sequencing tumor DNA and using the data to identify immune targets for unique, personalized cancer vaccines — from the research sphere onto a path toward commercialization.

From Genentech's position, staking a claim in personalized vaccines opens up an opportunity to lead the market in a new type of therapeutic, but also potentially to bolster the effectiveness of existing immunotherapies in its portfolio.

Peter Fong, associate director of oncology business development at Genentech, told GenomeWeb in an email this week that the company has recognized that there is increasing evidence that the activity of checkpoint inhibitors correlates with a pre-existing immunity against a patient's tumor.

"By vaccinating patients against neoantigens present on their tumors and thus inducing anti-tumor immunity, the depth and breadth of checkpoint inhibitor response (such as PDL-1 and PD-1) may be significantly enhanced."

Moreover, "unlike any other medicine we have ever developed, it is possible that all patients diagnosed with cancer, regardless of tumor type, may benefit from these individually tailored, personalized vaccines," he added.

If genomically personalized vaccines move successfully into commercial production and clinical use, it will require adaptation on the part of regulators to a new drug-diagnostic paradigm, Sean Marett, BioNTech's chief operating officer, told GenomeWeb.

With personalized vaccines, the therapy itself is indelibly linked to a diagnostic process (genome sequencing) much more so than personalized medicines that require a molecular or genetic test to guide their use.

Unlike other cancer vaccines targeting 'self' antigens expressed by both tumor cells and normal healthy cells, which have struggled in development, platform's like BioNTech's are designed to target the neoantigens linked to tumor-specific mutations.

BioNTech's vaccine development platform is called IVAC (short for individualized vaccines against cancer) Mutanome, and uses next-generation sequencing to identify mutations specific to a particular patient's cancer. That information then supports the development of a personalized mRNA vaccine that is designed to trigger an immune response.

Under their newly announced collaboration, BioNTech said that it and Genentech will work together to continue to develop and test personalized vaccines using IVAC Mutanome.

Marett said that the company's competitive interests preclude discussing its approaches in detail, but BioNTech is not the only entity tackling personalized cancer vaccines using comprehensive sequencing.

A University of Washington group led by Elaine Mardis, for example, published a proof-of principle study in Science Express last year in which they treated three individuals with stage III cutaneous melanoma with dendritic cell-based vaccines that they designed based on patients' cancer genomes.

Mardis and colleagues' method for identifying vaccine-targetable neoantigens involves analyzing exome sequences of matched tumor and normal samples from each patient, predicting the peptides that would be produced from the mutations that appear in the tumor, and then narrowing down that list of potential neoantigens based on their anticipated interactions with the immune system.

Describing their approach, called pVAC-Seq, in Genome Medicine earlier this year, the UW group said they also perform RNA sequencing to determine whether a variant is expressed in the tumor and to track isoform-level expression.

Genentech also is not alone among the bigger pharmaceutic firms in taking an interest in personalized cancer vaccines. Bristol-Myers Squibb, for example, inked a collaboration with Massachusetts-based Neon Therapeutics in late 2015 to evaluate the combination of Neon's personalized vaccine technology, called NEO-PV-01, with BMS's Opdivo (nivolumab).

Other early personalized vaccine developers are working on their own, but may yet attract deals by larger pharma companies. Two of these firms, Immune Design and Gritstone Oncology, signed a research collaboration in May of this year, aimed at combining their technologies.

In the announcement of the deal with Genentech last month, BioNTech said that the partnership will include studies combining IVAC Mutanome-developed drugs with other therapeutics in a variety of cancer types.

According to Fong, the two partners hope to start a Phase I combination trial pairing Genentech's anti-PDL1 cancer immunotherapy Tecentriq (atezolizumab) with vaccines developed using IVAC Mutanome. According to the firms, this trial will take place in 2017 and will include a variety of cancer types.

"While we cannot provide specifics at this time, we hope to combine mRNA cancer vaccine technology with multiple investigational immunotherapies that we currently have in research and/or clinical development," Fong added in his email.

Other groups are also interested in similar combined approaches using personalized vaccines to increase the efficacy or broaden the population that can benefit from immunotherapies. Mardis and colleagues at UW, for example, have been extending their work in melanoma patients by combining personalized vaccines with PD-1 checkpoint inhibitors — and are exploring the same strategy in breast cancer, pancreatic cancer, and pediatric cancers.

Fong declined to comment on how the partnership between Genentech and BioNTech would function if and when the two companies are able to bring personalized vaccines to market — whether BioNTech would serve as a diagnostic partner, performing the sequencing of patients and creating vaccines using IVAC mutanome, or whether the entire process would be centralized under Genentech's purview.

According to Marett, personalized cancer vaccines pose commercialization and regulatory challenges that more traditional personalized medicines do not. However, he said that BioNTech is confident in the scalability of its approach and of the abilities of its new partner.

"There have been a number of [publications] in the literature about neoantigens and their value in treating cancer," he said. "It's really caught the imagination of a number of pharma companies, but for us, Genentech is a really good partner and the partner of choice because they have demonstrated again and again that they can bring innovative products to the market."

However, Marett said, personalized tumor neoantigen-based vaccines are still a largely unexplored terrain. "Each patient gets a different product, because everyone's tumor is different, so it is indelibly linked, the diagnostic with the [drug]," he said.

"It's really something that is quite unusual in the pharma space," he added. "You have to get the pharmaceutical side right in terms of delivery, efficacy, side effects … and then the other aspect is all the logistics around the diagnostic, and the whole aspect of selecting the right neoepitopes. That is what really drives the efficacy."

Marett said that BioNTech has had positive feedback from European regulators in response to the outcomes of its own early clinical trials.

"We've already completed one clinical trial using this approach in Europe. …. Based on that I can tell you that the regulators are extremely supportive of this approach," Marett said.

He also said that BioNTech has been doing early payor research in Germany to gauge the potential reception of individualized cancer vaccines by insurers.

So far, he said, "They are also quite supportive, because they know that [with these vaccines] we are really tailor making something for that patient so there is none of that 'will it work or wont it work?'"

Though BioNTech is ahead of the pack in terms of clinical testing so far, other groups are not far behind. Neon Therapeutics announced this summer that it had filed an Investigational New Drug application for NEO­PV­01 with the US Food and Drug Administration, enabling it to initiate a multicenter Phase 1b trial of its vaccines with BMS's Opdivo.