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Back when viruses were discovered in the 19th century, they were seen as nothing more than disease-causing pathogens. But with the discovery of oncolytic viruses, it became clear that some viruses can be harnessed to hijack and destroy tumor cells while leaving healthy cells unaffected. This past year has seen various developments in the field of oncolytic virus therapies, be it in clinical trials, licensing deals, or candidates being awarded various regulatory designations.
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Calidi Biotherapeutics’ oncolytic virus CLD-201 bags FDA fast track designation
For instance, California-based Calidi Biotherapeutics’ oncolytic virus CLD-201 was awarded fast track designation from the U.S. Food and Drug Administration (FDA) three days ago. The fast track designation helps accelerate the approval of these medicines. The candidate CLD-201 is a stem cell-loaded oncolytic virus, and it bagged the title from the FDA for treating soft tissue sarcoma, a rare type of cancer that develops in the body’s soft tissues, such as muscles, fat, blood vessels, and nerves.
Calidi’s CLD-201 is made up of adult stem cells that have been derived from fat tissues and loaded with oncolytic vaccinia virus. Stem-cell loading of an oncolytic virus helps protect the virus from being cleared by the body’s immune system and amplifies it within the stem cell. This has been found to elevate its potency, immune activation, and efficacy in preclinical animal models, according to Calidi.
“This designation underscores the unmet medical need in sarcoma and provides scientific and regulatory validation of CLD-201. We believe CLD-201 has the potential to provide durable and transformational treatment to patients with sarcoma as well as patients with other advanced tumor types,” said Guy Travis Clifton, chief medical officer (CMO) of Calidi.
Like CLD-201, Calidi’s oncolytic virus pipeline is born out of its platform technology. The viruses are delivered to the tumor cells by the stem cells, which then go on to infect and kill the harmful cells. Calidi has explained that its pipeline of oncolytic viruses has another perk. They turn cold tumors hot, meaning that they have the capacity to make tumors more responsive to immunotherapy because they are more susceptible to immune cell infiltration.
Oncolytics Biotech reveals promising data on pelareorep
Also last month, Oncolytics Biotech revealed translational data of its oncolytic virus pelareorep’s effectiveness across different tumor indications. Pelareorep was found to replicate in cancer cells, activate immune pathways, and drive T cell expansion and tumor infiltration in immunotherapy-resistant cancers.
Specifically, blood and tumor samples were taken from patients with pancreatic ductal adenocarcinoma (PDAC) and other gastrointestinal cancers – cancers that affect the digestive system. The samples showed an increase in interferons – proteins that play a key role in the body’s immune response – and more immune cells called tumor-infiltrating lymphocytes (TILs) being mobilized to shrink tumors. Moreover, cold tumors managed to turn hot.
“The collection of data here shows that pelareorep works how a cancer immunotherapy should work,” said Jared Kelly, CEO of Oncolytics. “Pelareorep is a versatile product candidate with strong platform potential to enhance immunological responses in multiple indications, including hard-to-treat cancers.”
Engineered oncolytic viruses over naturally occurring ones? CG Oncology raises bar in bladder cancer care
Pelareorep, unlike CLD-201, is not engineered and is naturally occurring. In the case of oncolytic viruses, the ability to manipulate a naturally occurring virus’ genetic material can be taken advantage of. A research paper published in the National Library of Medicine explained that this finetuning can improve target specificity.
For instance, talimogene laherparepvec, known by its brand name Imlygic and was the first oncolytic viral therapy that nabbed FDA approval in 2015, has been genetically modified to preferentially target cancer cells. By engineering it to produce an immune factor called the granulocyte macrophage colony-stimulating factor (GM-CSF), it was designed to improve the antitumor immune response.
Nowadays, more biotechs are developing engineered oncolytic viruses. California-based CG Oncology came out with durability data for its engineered oncolytic virus immunotherapy cretostimogene grenadenorepvec in April. A 42.3% complete response rate was achieved in patients with bladder cancer who took the therapy. Around 58.3% of patients showed durable complete responses and in 97.3% of all the patients treated with the immunotherapy, the disease did not progress after two years.
CG Oncology has upped the game for bladder cancer care in recent times. Their oncolytic virus elicited a 75.2% complete response rate in phase 3 studies last year. This further cemented optimism among investors after CG went public for $380 million.
Investors spend millions on Genelux and Tilt Biotherapeutics
Just before CG’s positive results for cretostimogene grenadenorepvec this year, another California-based company, Genelux, revealed promising preliminary phase 1b/2 results of its oncolytic virus therapy Olvi-Vec for small-cell lung cancer, a rare aggressive form of lung cancer. It is a modified form of the oncolytic vaccinia virus, which has a large engineering capacity, and was discovered from Genelux’s library consisting of more than 500 different oncolytic vaccinia constructs and strains.
The initial findings saw a 71% disease control rate in the dose escalation cohorts. All participants with disease control experienced a reduction in all lesions, and the size of the tumor reduced by around 79% in one patient, Genelux reported.
At lower dose cohorts, three participants, one of whom had undergone different kinds of treatments prior to the Olvi-Vec trial, had their tumors shrink by between 24% to nearly 30%.
The announcement of the encouraging study outcomes went hand-in-hand with a $10.5 million public offering in late March. Another oncolytic virus therapy biotech that racked up funds this year was Tilt Biotherapeutics. The Finnish company closed a $25 million series B financing round in May, which is fueling its candidate TILT-123’s phase 2 trial in ovarian cancer.
As ovarian cancer is generally highly resistant to immunotherapy, with immune checkpoint inhibitors reaping disappointing outcomes in studies – they only work in around one in 10 patients – Tilt is betting on oncoyltic viruses to trigger immune responses in tumors and destroy them. Its lead asset TILT-123 is engineered and has been armed with two signaling proteins called cytokines, making it the first of its kind.
“We’ve been making good progress in ovarian cancer and this financing will support the rollout of our phase 2 clinical trials. Ovarian cancer continues to be an unmet medical need despite recent therapies being approved,” said Akseli Hemminki, founder and CEO of Tilt, in a press release. “There are no oncolytic viruses or checkpoint inhibitors currently approved for use in this indication. We are committed to our mission to transform the treatment options for patients with ovarian cancer with TILT-123.”
Ongoing phase 2 trials are piggybacking off positive phase 1 results, which were presented at ASCO 2024. The intravenously delivered candidate managed to set off an immune response against the cancer cells. Tilt was previously awarded a $2 million grant from the U.S. Department of Defense last year to assess the candidate in combination with an immunotherapy.
Oncolytic virus therapy: UroGen Pharma spends $4 million on IconOVir Bio’s ICVB-1042
Meanwhile, UroGen Pharma has bought IconOVir Bio’s ICVB-1042, an engineered oncolytic adenovirus to treat bladder cancer, from California-based IconOVir Bio for $4 million. For the New York-based cancer therapeutics company, this oncolytic virus adds to its bladder cancer-focused pipeline.
The treatment of bladder cancer has long been shaped by immunotherapy approaches such as Bacillus Calmette-Guérin (BCG) therapy – involves the delivery of a weakened strain of BCG directly into the bladder via a catheter to trigger an immune response against cancer cells – explained Mark Schoenberg, chief medical officer of UroGen. However, unlike BCG therapy, ICVB-1042 has the potential to selectively destroy cancer cells while retaining potency.
“ICVB-1042 may represent an exciting leap forward, with several attributes we believe differentiate this asset from other oncolytic viruses,” Schoenberg had said in a press release this year.
Also this year, Maryland-based Theriva Biologics shifted gears to focus on its oncolytic virus therapy pipeline. While its recombinant protein ribaxamase has been making progress, its viral candidate VCN-01 is taking center stage for now. The adenovirus has previously been granted Orphan Drug designation from the EMA and both Orphan Drug and Fast Track designations from the FDA for the treatment of pancreatic cancer, as well as Orphan Drug and Rare Pediatric Diseases designations from the FDA for the treatment of retinoblastoma, a rare cancer that affects the eye.
Theriva secured a $7.5 million public offering in May, adding to the $11.6 million it had in cash back in March to push clinical development.
As the field seems to be buzzing with clinical progress and fundraising, French company Transgene and Swedish company BioInvent plan to debut its vaccinia-based candidate BT-001’s progress in phase 1 studies in solid tumors at the ESMO Congress in Berlin in October.
Candel Therapeutics hopes for FDA win for CAN-2409
All of this follows after Candel Therapeutics’ adenovirus CAN-2409 efficacious phase 3 results in prostate cancer late last year, where it met the primary endpoint by demonstrating statistically significant improvement in disease-free survival in patients who received CAN-2409 along with a prodrug and standard of care compared to standard of care alone.
This was followed by a $92 million public offering in December and a $15 million registered direct offering in June this year. Now the Massachusetts-based company is working with the FDA to seek approval for the viral therapy.
And while Replimmune’s skin cancer candidate’s FDA rejection has been a blow to the field this year – RP1 was rejected based on the FDA’s claims that the phase 3 trial was faulty – there’s no stopping progress in the sector. Although still regarded as an emerging cancer treatment approach, with many clinical candidates in their early stages of development, considering how fast-growing of a space cancer care is, we’ll be keeping an eye out on the growing R&D in the field.
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