NEW YORK – A clinical trial collaboration with Anixa Biosciences could open the way for Verdi Solutions to seek approval of its peptide cancer vaccines in the US and Europe.
Vienna-based Verdi is developing personalized cancer vaccines, but unlike most competing products, its vaccines are not only based on tumor neoantigens but also target overexpressed tumor antigens and viral antigens. The firm identifies these vaccine targets in the patient's tumor using transcriptomic profiling and designs multiple peptide vaccines for individual patients, which are given simultaneously to address tumor heterogeneity, according to Verdi CEO Julianna Lisziewicz.
Verdi, founded in 2021, uses its artificial intelligence platform to select unique targets within a patient's cancer based on RNA sequencing of a tumor sample. The algorithm then searches Verdi's proprietary database of qualified vaccine targets to identify potential targets for the patient. It then models the mechanisms of tumor-specific immune responses for each individual and tailors a set of vaccines specifically for that patient.
In parallel with its personalized cancer vaccine program, Verdi is also developing off-the-shelf cancer vaccines and pairing them with companion diagnostics that can identify likely responders and optimize treatment outcomes.
The firm has thus far developed personalized cancer vaccines using data from primary tumors for three patients with bone metastases through a compassionate use program available in some European countries called Individueller Heilversuch (Individual Healing Attempt). Through the program, doctors can prescribe experimental personalized treatments to patients with life-threatening conditions who lack satisfactory approved therapy options.
Two of the patients Verdi has treated had breast cancer and one had gastric cancer. Lisziewicz noted that bone metastases are very painful, and there is no curative treatment available for them. However, among the patients treated under Individueller Heilversuch, Verdi saw improvement in all three. "We found it a very interesting observation, which gives us an opportunity to run clinical trials," Lisziewicz said. The company hopes to confirm these preliminary results through further study and has discussed with the US Food and Drug Administration the possibility of seeking expedited approval.
The challenge with that, in Lisziewicz's view, is that neither the FDA nor the European Medicines Agency has much experience regulating this type of personalized vaccine. Verdi's personalized vaccine approach does not fit into any established regulatory framework, she said. For vaccines, regulatory agencies approve a single vaccine agent for a large population, catering to the average patient. "But there is no average patient," Lisziewicz said. "We are making many vaccines for one patient." And because the peptides for those vaccines are chosen from among a quadrillion possible peptides, each individualized vaccine cocktail will be unique.
That's why Verdi is looking to partner with San Jose, California-based Anixa to advance an off-the-shelf vaccine developed using the same technology with an AI-based companion diagnostic to identify likely responders. They hope to blaze a trail for Verdi's personalized vaccines, while generating evidence for the newer off-the-shelf product. The firms will conduct a trial in the US to evaluate whether the vaccine can shrink tumors and improve patients' quality of life.
"This fits much more in the current pharmaceutical [regulatory framework] than the completely personalized vaccine, because a drug with a companion diagnostic has a very clear pathway for market approval," Lisziewicz said.
However, Verdi and Anixa will still be pushing the boundaries from a regulatory standpoint by asking the FDA to consider quality of life as an endpoint for accelerated approval rather than traditional efficacy endpoints like progression-free survival. Lisziewicz pitched the idea to the FDA in January and provided results from the three European patients treated with personalized vaccines under Individueller Heilversuch to demonstrate how reduction in pain improved their quality of life. For drugs with accelerated approval that are approved based on their impact on surrogate endpoints, companies currently must submit post-market data showing the drug improves traditional outcomes like progression-free survival in order to achieve regular approval and remain on the market.
To Lisziewicz's proposal, FDA regulators said that they had never approved a cancer drug based on quality of life before. "Of course you didn't," Lisziewicz recalled responding, adding that cancer drugs are typically so toxic that they ruin a patient's quality of life in the attempt to prolong survival. But Verdi's peptide vaccines, in comparison, have shown minimal toxicity. Side effects in the three patients treated so far included "some skin toxicity or low fever," Lisziewicz said, "like a childhood vaccine."
The FDA told Lisziewicz that was a "good argument," and she should collect more evidence, which she aims to do under a partnership with Anixa.
Anixa CEO Amit Kumar said Verdi's results in European patients piqued the company's interest in a partnership. Anixa signed a letter of intent with Verdi last week, under which Anixa has a six-month exclusive right to negotiate a deal to develop and personalize an off-the-shelf cancer vaccine.
The program, if Anixa decides to exercise its rights, could complement the cancer vaccines it is developing with Cleveland Clinic and the immunotherapies it is making with Moffitt Cancer Center based on its proprietary chimeric endocrine receptor T-cell (CER-T) technology, a type of chimeric antigen receptor (CAR) T-cell therapy. If Anixa exercises its rights under the letter of intent, it will collaborate with Verdi on vaccine trials in the US while Verdi continues advancing individualized treatments for cancer patients in Europe.
Kumar said the letter of intent gives Verdi some flexibility to negotiate with other "very large" partners, which the companies have not disclosed. "We want to help Verdi not only develop the technology but also establish these partnerships," Kumar said. "We have six months to sign a partnership that's mutually beneficial to both of us."
For the off-the-shelf vaccine that the companies will codevelop, the focus will initially be on seeking regulatory approval in the US. "Of course, once we move forward in the US, Europe is a large market, as well, and we want to eventually go there," Kumar said.